JP2022515321A - Coated and / or impregnated ureteral catheter or stent and method - Google Patents

Abstract

(A) Proximal and (b) Distal, containing at least one protected drainage hole, port, or perforation, with at least mucosal tissue in response to the application of negative pressure through the catheter. A distal portion with a retaining portion, and at least a portion of the protective surface area, configured to establish an outer margin or protective surface area that prevents obstruction of one protected drain hole, port, or perforation. At least one coating, including at least one coating on and / or at least one impregnation thereof, comprising at least one of a lubricant, an antibacterial material, a pH buffer, or an anti-inflammatory material. A coated and / or impregnated urinary catheter or urethral stent device, including and / or with at least one impregnation.

Description

(Mutual reference of related applications)
This application is filed on February 25, 2016, US Provisional Application Nos. 62 / 300,025, and January 14, 2016, which are incorporated herein by reference in their entirety. US Provisional Application No. 62 / 278,721, US Provisional Application No. 62 / 260,966 filed on November 30, 2015, and US Provisional Application No. 62 / filed on July 20, 2015. A US patent application filed on January 20, 2017, which is a partial continuation of US Patent Application No. 15 / 214,955 filed on July 20, 2016, claiming the interests of No. 194,585. A partial continuation of US Patent Application No. 15 / 687,064 filed on August 25, 2017, which is a partial continuation of No. 15 / 411,884, filed on January 25, 2018. November 26, 2019, which is a partial continuation of US Patent Application No. 15 / 879,770, which is a partial continuation of US Patent Application No. 16 / 206,389 filed on November 30, 2018. Claims priority from US Patent Application No. 16 / 696,026 filed on the same day.

Also, US Patent Application No. 15 / 879,770, filed January 25, 2018, was filed February 25, 2016, which is incorporated herein by reference in its entirety. US Provisional Application No. 62 / 300,025, US Provisional Application No. 62 / 278,721 filed on January 14, 2016, US Provisional Application No. 62/260 filed on November 30, 2015, US Patent Application No. 15 / 214,955 filed July 20, 2016, claiming the interests of US Provisional Application No. 966 and US Provisional Application No. 62 / 194,585 filed July 20, 2015. A partial continuation of US Patent Application No. 15 / 411,884 filed on January 20, 2017, which is a partial continuation of the US Patent Application No. 15 / filed on August 25, 2017. It is a partial continuation of No. 687,083.

Also, U.S. Patent Application Nos. 15 / 879,770, filed January 25, 2018, are incorporated herein by reference in their entirety.
US Provisional Application No. 62 / 300,025 filed on February 25, 2016, US Provisional Application No. 62 / 278,721 filed on January 14, 2016, filed on November 30, 2015. Filed on July 20, 2016, claiming the interests of US Provisional Application No. 62 / 260,966 and US Provisional Application No. 62 / 194,585 filed July 20, 2015. It is a partial continuation of US Patent Application No. 15 / 745,823 filed on January 18, 2018, which is the US stage of PCT / US 2016/043101.

In addition, US Patent Application No. 15 / 879,770 filed on January 25, 2018, US Provisional Application No. 62 / 489,789 filed on April 25, 2017, and April 2017. Claims the benefit of US Provisional Application No. 62 / 489,831 filed on 25th.

The present disclosure relates to catheters and / or stent devices for deployment in the patient's urinary tract, in particular at least one coating and / or to improve the ease and function of insertion of the catheter and / or stent device. Or with respect to a device with impregnation.

The kidneys or urinary system include a pair of kidneys, each kidney connected to the bladder by the ureter and to the urethra for draining fluid or urine produced by the kidneys from the bladder. The kidneys perform several important functions for the human body, including, for example, filtering blood and eliminating waste in the form of urine. The kidney also regulates electrolytes (eg, sodium, potassium, and calcium) and metabolites, blood volume, blood pressure, blood pH, fluid volume, red blood cell production, and bone metabolism. A proper understanding of the biological structure and physiology of the kidney is useful for understanding the effects of altered hemodynamics and other volume overload conditions on its function.

In normal anatomy, the two kidneys are located after the peritoneum in the abdominal cavity. The kidney is a bean-shaped encapsulated organ. Urine is formed by the renal unit, which is the functional unit of the kidney, and then flows through a convergent tubular system called the collecting duct. The collecting ducts join together to form the small calyx, then the calyx, and finally near the concave part of the kidney (renal pelvis). The main function of the renal pelvis is to direct the urinary flow to the ureter. Urine flows from the renal pelvis into the ureter, a tubular structure that transports urine from the kidneys into the bladder. The outer layer of the kidney, called the exodermis, is a rigid fibrous encapsulation. The inside of the kidney is called the medulla. The medulla structure is arranged in a cone.

Each kidney consists of about one million kidney units. Each renal unit includes a glomerulus, Bowman's capsule, and renal tubules. The tubules include a proximal tubule, a loop of Henle, a distal convoluted tubule, and a collecting duct. The renal unit contained in the exodermis layer of the kidney is distinctly different from the biological structure of what is contained in the medulla. The main difference is the length of the loop of Henle. The medullary kidney unit contains a longer loop of Henle, which allows for better regulation of water and sodium reabsorption than the integumental kidney unit under normal conditions.

The glomerulus is the origin of the renal unit and is involved in the initial filtration of blood. Afferent arterioles allow blood to pass through glomerular capillaries, where hydrostatic pressure pushes water and solutes into Bowman's capsule. The net filtration pressure is expressed as the hydrostatic pressure in the afferent arteriole minus the hydrostatic pressure in the Bowman's space, minus the osmotic pressure in the efferent arteriole.
Net filtration pressure = hydrostatic pressure (afferent arteriole) -hydrostatic pressure (Bowmann gap) -osmotic pressure (efferent arteriole) (Equation 1)

The magnitude of the net filtration pressure defined by Equation 1 determines the amount of extrafiltration fluid formed in the Bowman's space and delivered to the renal tubules. The remaining blood exits the glomerulus via the efferent arterioles. Normal glomerular filtration, i.e., delivery of the extrafiltration fluid into the renal tubules is about 90 ml / min / 1.73 m ² .

The glomerulus has a three-layer filtration structure and includes vascular endothelium, glomerular basement membrane, and podocytes. Normally, giant proteins such as albumin and red blood cells are not filtered into Bowman's space. However, rising glomerular pressure and glomerular stromal dilation result in surface area changes on the basement membrane, allowing larger fenestrations between podocytes to allow larger proteins to pass through Bowman's space. do.

The extrafiltration fluid collected in the Bowman's space is first delivered to the proximal tubule. Reabsorption and secretion of water and solute in the renal tubules is carried out by mixing active transport channels and passive pressure gradients. Proximal tubules usually reabsorb most of the sodium chloride and water and almost all glucose and amino acids filtered by the glomerulus. The loop of Henle has two components designed to concentrate waste in the urine. The descending limb is highly permeable and reabsorbs most of the remaining water. The ascending limb reabsorbs 25% of the remaining sodium chloride and produces concentrated urine, for example in terms of urea and creatinine. Distal convoluted tubules usually reabsorb a small percentage of sodium chloride, resulting in a osmotic gradient that is followed by water.

Under normal conditions, net filtration is about 14 mmHg. The effect of venous stasis can be a significant reduction in net filtration up to about 4 mmHg. Jessup M. , The cardioreral syndrome: Do we need a change of strategy or a change of tactics? , JACC 53 (7): 597-600, 2009 (hereinafter “Jessup”). The second filtration step occurs in the proximal tubule. Most of the secretion and absorption from urine occurs in the renal tubules within the medulla renal unit. Active transport of sodium from the renal tubules into the interstitial space initiates this process. However, hydrostatic power influences the net exchange of solutes and water. Under normal conditions, 75% of sodium is thought to be reabsorbed into the lymphatic or venous circulation. However, because the kidney is encapsulated, it is sensitive to changes in hydrostatic pressure from both venous and lymphatic stasis. During venous stasis, sodium and water retention can exceed 85% and further prolong renal stasis. Verbruge et al. , The kidney in kidney heart failure: Are natururesis, sodium, and diruetucs really the good, the bad and the ugly? See European Journal of Heart Failure 2014: 16,133-42 (hereinafter "Verbrugge").

Venous stasis can lead to the prerenal form of acute renal injury (AKI). Prerenal AKI results from loss of perfusion (or loss of blood flow) through the kidney. Many clinicians focus on the lack of flow into the kidney due to acute circulatory insufficiency. However, there is also evidence that lack of blood flow from organs due to venous stasis can also be a clinically significant persistent injury. Dammann K, Import of venous connection for forcing relative failure in advanced decompensated heart failure, JACC 17: 589-96, 2009 (see D).

Prerenal AKI occurs across various diagnoses and requires critical care hospitalization. The most prominent hospitalizations are for sepsis and acute decompensated heart failure (ADHF). Additional hospitalizations include cardiovascular surgery, general surgery, cirrhosis, trauma, burns, and pancreatitis. The symptoms of these disease states vary widely in clinical practice, but what they have in common is an increase in central venous pressure. In the case of ADHF, the increase in central venous pressure caused by heart failure leads to pulmonary edema, followed by dyspnea, which in turn promotes hospitalization. In the case of sepsis, the increase in central venous pressure is primarily the result of large doses of rapid infusion. Persistent injury is venous stasis, resulting in improper perfusion, regardless of whether the primary invasion is hypovolemia due to hypovolemia or sodium and fluid retention.

Hypertension is another widely recognized condition that causes perturbations within the active and passive transport systems of the kidney. Hypertension directly affects afferent arteriole pressure, resulting in a proportional increase in net filtration pressure in the glomerular body. The increased filtration rate also increases peritubular capillary pressure, which stimulates sodium and water reabsorption. See Verbruge.

Because the kidney is an encapsulated organ, it is sensitive to changes in pressure within the medullary pyramid. Elevated renal vein pressure results in stasis leading to increased interstitial pressure. The increase in interstitial pressure exerts force on both the glomerulus and the renal tubules. See Verbruge. In the glomerulus, the increase in interstitial pressure directly opposes filtration. Increased pressure increases interstitial fluid, thereby increasing hydrostatic pressure in the interstitial fluid in the renal medullary and the peritubular capillaries. In both cases, hypoxia can ensure that it leads to cytotoxicity and further loss of perfusion. The net result is a further deterioration of sodium and water reabsorption, with negative feedback. See Verbruge (133-42). In particular, volume overload in the abdominal cavity is associated with many diseases and conditions, including elevated intra-abdominal pressure, abdominal compartment syndrome, and acute renal failure. Volume overload can be addressed through renal replacement therapy. Peters, C.I. D. , Short and Long-Term Effects of the Angiotensin II Receptor Blocker Irbesartanon Intradialytic Central Hemodynamics: A Randomized Double-Blind Placebo-Controlled One-Year Intervention Trial (SAFIR Study), PLoS ONE (2015) 10 (6): e0126882. doi: 10.131 / journal. pone. See 0126882 (hereinafter “Peters”). However, such clinical strategies do not provide improvement in renal function in patients with cardiorenal syndrome. See Bart B, Ultrafiltration in decompensated heart failure with cardioral syndrome, NEJM 2012; 367: 2296-2304 (hereinafter “Bart”).

Systems to improve the removal of fluids such as urine from patients, specifically to increase the amount and quality of fluid output from the kidneys, in the light of such problematic effects of fluid retention. A method is needed.

The present disclosure improves on previous devices / systems by providing coatings and / or impregnated devices such as stents or catheters for deployment in the patient's renal pelvis, kidney, and / or urinary tract.

In some embodiments, a coated and / or impregnated urinary catheter or urethral stent device is provided, (a) a proximal portion and (b) a distal portion, at least one protected drain. Outer marginal or protective surface area with a hole, port, or perforation that prevents mucosal tissue from obstructing at least one protected drain hole, port, or perforation in response to the application of negative pressure through the catheter. At least one coating and / or at least one impregnation inside it, with a distal portion and at least a portion of the protective surface area, comprising a retaining portion, which is configured to establish a lubricant, antibacterial. It comprises at least one coating and / or at least one impregnation, comprising at least one of a sex material, a pH buffer, or an anti-inflammatory material.

In some embodiments, a coated urinary catheter or urethral stent device is provided, (a) a proximal portion and (b) a distal portion, at least one protected drain hole, port,. Or with a perforation to establish an outer peripheral edge or protective surface area that prevents mucosal tissue from obstructing at least one protected drainage hole, port, or perforation in response to the application of negative pressure through the catheter. It comprises a distal portion, comprising a retention portion, and a coating comprising at least one coating over at least a portion of the protective surface area, comprising a lubricant and a pH buffering material.

In some embodiments, methods of making a coated and / or impregnated catheter or stent device are provided, the method of applying at least one sublayer of the coating to at least a portion of the catheter or stent. The step and at least one outermost layer of the coating comprising at least one of the antibacterial material and the pH buffering material, wherein the at least one sublayer is on at least a portion of the at least one sublayer. The step of application, at least one outermost layer, comprises a step, including a lubricant.

Non-limiting examples, aspects, or embodiments of the invention will now be described in the appendices numbered below.

Appendix 1: A coated and / or impregnated urinary catheter or urethral stent device, (a) a proximal portion and (b) a distal portion, at least one protected drain, port, or. To establish an outer peripheral edge or protective surface area that comprises a perforation and prevents mucosal tissue from obstructing at least one protected drainage hole, port, or perforation in response to the application of negative pressure through the catheter. At least one coating and / or at least one impregnation inside it, consisting of a distal portion with a retaining portion and at least a portion of the protective surface area, such as a lubricant, an antibacterial material, a pH buffer. A device comprising at least one coating and / or at least one impregnation, comprising at least one of an agent or an anti-inflammatory material.

Appendix 2. The device according to Appendix 1, wherein the at least one lubricant is configured to be lubricious in the presence of a fluid.

Appendix 3. The device according to Appendix 1 or 2, wherein the at least one lubricant comprises a hydrophilic material.

Appendix 4. The device according to Appendix 3, wherein the hydrophilic material comprises a gel.

Appendix 5. The at least one lubricant is polyethylene glycol, polyvinylpyrrolidone, polytetrafluoroethylene, polyvinyl alcohol, polyacrylamide, polymethacrylic acid, acrylic polymers or copolymers thereof, polyelectrolytes, hydrogels containing polyacrylic acid, and / or disulfides. The device according to any of Annex 1-4, comprising at least one of cross-linking (poly (oligo (ethylene oxide) monomethyl ether methacrylate).

Appendix 6. The device according to any of Annex 1-5, wherein the at least one lubricant comprises at least one of polytetrafluoroethylene, siloxane, silicone, or polysiloxane.

Appendix 7. The device according to any of Annex 1-6, wherein the at least one coating and / or impregnation comprises at least one outermost layer, comprising at least one lubricant.

Appendix 8. The at least one coating and / or impregnation further comprises at least one sublayer located between the protective surface area of the device and the at least one outermost layer, the at least one sublayer comprising at least one antibacterial material. The device according to any of Supplementary note 1-7, including.

Appendix 9. At least one lubricant dissipates into the surrounding fluid or tissue over time, thereby exposing at least one sublayer to the fluid and / or tissue surrounding the deployed device, Appendix 1-8. The device described in any of.

Appendix 10. The device according to any of Annex 1-9, wherein the at least one lubricant dissipates over a period of 1 to 10 days following insertion of the device into the patient's urinary tract.

Appendix 11. Any of Appendix 1-9, wherein at least one antibacterial material in at least one sublayer is configured to be released into the surrounding fluid or tissue, depending on the dissipation of at least one lubricant in the outermost layer. The device described in.

Appendix 12. The device according to Annex 8, wherein the at least one antibacterial material in at least one sublayer is configured for sustained release into the surrounding fluid or tissue over a period of about 1 day to about 1 year.

Appendix 13. The at least one sublayer is a first sublayer that is applied to the protective surface area of the device and covers at least a portion of the first sublayer and the first sublayer, including a pH buffering material. The device according to Appendix 8, further comprising a second sublayer, comprising at least one antibacterial material.

Appendix 14. 13. device.

Appendix 15. The at least one antibacterial material is at least one of chlorhexidine, silver ion, nitrogen oxide, bacteriophage, sirolimus, heparin, phosphorylcholine, silicon dioxide, diamond-like carbon, caspopofangin, chitosan, organosilane, sulfonamide, or antibacterial peptide. The device according to any of Annex 1-14, including one.

Appendix 16. The device according to Appendix 14, wherein the at least one antibiotic material comprises at least one of amdinocillin, levofloxacin, penicillin, tetracycline, sparfloxacin, or vancomycin.

Appendix 17. The device according to any of Annex 1-16, wherein the at least one antibacterial material comprises at least one antibacterial material and at least one antibiotic material.

Appendix 18. The device according to any of Annex 1-17, wherein the at least one coating and / or impregnation comprises at least one lubricant and at least one antibacterial material.

Appendix 19. The device of Appendix 18, wherein the at least one lubricant is present in the outermost layer of the coating.

Appendix 20. The device according to any of Annex 1-19, wherein the at least one antibacterial material resides within a sublayer of the coating located between the protective surface area of the device and the outermost layer of the coating.

Appendix 21. The at least one coating is located on the innermost layer, which is the innermost layer and contains at least one hydrophilic material, and is located on at least a portion of the innermost layer, which is located on a portion of the protective surface area of the device. A first sublayer containing at least one antibacterial material and at least one second sublayer containing at least one antibiotic material located on at least one first sublayer and a second. A third sublayer located on the sublayer, the third sublayer containing at least one antibacterial material, and an outermost layer located on the third sublayer, at least. The device according to Appendix 1, comprising an outermost layer comprising one hydrophilic material.

Appendix 22. The sublayer containing the antibacterial material is configured for sustained release of at least one antibacterial material into the fluid or tissue surrounding the device for a period of at least 24 hours and at least one antibiotic material. 21. The device according to Annex 21, wherein the at least one second sublayer is configured to release at least one antibiotic material into the fluid or tissue surrounding the device for a period of less than 24 hours. ..

Appendix 23. The device according to any of Annex 1-22, wherein the at least one pH buffer comprises at least one of sodium citrate, sodium acetate, or sodium bicarbonate.

Appendix 24. The device according to any of Annex 1-23, wherein the at least one anti-inflammatory material comprises at least one of dexamethasone, heparin, or alpha-melanocyte stimulating hormone (α-MSH).

Appendix 25. The at least one anti-inflammatory material is of a polyethylene glycol-containing polymer, poly (2-hydroxyethylmethacrylate), poly (N-isopropylacrylamide), poly (acrylamide), phosphorylcholine polymer, mannitol, oligomaltose, or taurine group. The device according to any of Annex 1-24, comprising at least one of them.

Appendix 26. The device according to any of Annex 1-25, wherein the device comprises at least one coating on at least a portion of the protected surface area.

Appendix 27. The device according to any of Annex 1-26, wherein the device comprises at least one impregnation within at least a portion of the protected surface area.

Appendix 28. The device according to any of Annex 1-27, wherein the device is a ureteral catheter.

Appendix 29. The device according to any of Annex 1-28, wherein the device is a bladder catheter.

Appendix 30. The device according to any of Annex 1-29, wherein the proximal end of the proximal portion of the device is configured to be directly or indirectly connected to a pump for applying negative pressure to the device.

Appendix 31. Devices include copper, silver, gold, nickel-titanium alloys, stainless steel, titanium, polyurethane, polyvinyl chloride, polytetrafluoroethylene (PTFE), latex, silicon coated latex, silicone, polyglycolide or poly (glycolic acid). ) (PGA), polylactic acid (PLA), poly (lactic acid-co-glycolic acid), polyhydroxyalkanoic acid, polycaprolactone, and / or poly (propylene fumarate), appendix 1-. The device according to any one of 30.

Appendix 32. At least one protected drain hole, port, or perforation is placed on the protected or inner surface area of the retention portion, the outer peripheral edge or protection surface area of the retention portion of the catheter supports the mucosal tissue, thereby supporting the mucosal tissue. , Any of Appendix 1-31, configured to prevent obstruction of one or more of the protected drain holes, ports, or perforations in response to the application of negative pressure through the ureteral catheter. The device described in.

Appendix 33. The retaining portion comprises one or more helical coils, each coil having an outward facing side and an inward facing side, the outer peripheral edge or protective surface area of the one or more helical coils. One of Annex 1-32, which comprises an outward facing side and at least one protected drain hole, port, or perforation is located on the inward facing side of one or more spiral coils. Described device.

Appendix 34. The device according to any of Supplementary note 1-33, wherein the retention portion is configured to extend to a deployment position where the diameter of the retention portion exceeds the diameter of the drainage lumen portion.

Appendix 35. The number of drain holes, ports, or perforations towards the distal end of the retention portion is greater than the number of drain holes, ports, or perforations towards the proximal end of the retention portion, as described in any of Appendix 1-34. Device.

Appendix 36. The size of one or more of the drain holes, ports, or perforations towards the distal end of the retention portion is one or more of the drain holes, ports, or perforations towards the proximal end of the retention portion. The device according to any of Appendix 1-35, which exceeds the size of the object.

Appendix 37. The total area of the drainage hole, port, or perforation towards the distal end of the retention portion exceeds the total area of the drainage hole, port, or perforation towards the proximal end of the retention portion, either Appendix 1-36. The device described in.

Appendix 38. The device according to any of Supplementary note 1-37, wherein the side wall of the proximal portion of the device has essentially no or no drainage opening.

Appendix 39. A coated urinary catheter or urethral stent device, (a) proximal and (b) distal, with at least one protected drain, port, or perforation through the catheter. A retention portion configured to establish an outer peripheral edge or protective surface area that prevents mucosal tissue from obstructing at least one protected drainage hole, port, or perforation in response to the application of negative pressure. A device comprising a distal portion and at least one coating over at least a portion of the protective surface area, comprising a lubricant and a pH buffering material.

Appendix 40. 39. The device of Appendix 39, wherein the coating comprises at least one outermost layer, comprising a lubricant.

Appendix 41. The device of Appendix 39, wherein the coating further comprises at least one sublayer, positioned between the catheter or stent and the outermost layer, wherein the at least one sublayer comprises a pH buffering material.

Appendix 42. A method of manufacturing a coated and / or impregnated catheter or stent device, in which at least one sublayer of the coating is applied to at least a portion of the catheter or stent, the at least one sublayer being antibacterial. A step comprising at least one of a sex material and a pH buffering material and a step of applying at least one outermost layer of the coating onto at least a portion of at least one sublayer, at least one outermost layer. Is a method, including a lubricant, a step and a method.

Appendix 43. The catheter or stent is configured to be deployed in the patient's urinary tract, and in the deployed position, the catheter or stent has a protected surface area and a protected surface area, and the coating is at least the protected surface area of the catheter or stent. 42. The method according to Appendix 42, which is applied to the above.

Appendix 44. 42. The method of Appendix 42, wherein the antibacterial material comprises at least one of an antibacterial material and an antibiotic material.

Appendix 45. Further steps to form at least one opening, hole, space, and / or microchannel on the distal portion of the catheter or stent and a deployable retention portion on the distal portion of the catheter or stent. The method according to Appendix 42, including.

Appendix 46. The step of applying at least one sublayer applies a first sublayer and includes at least one of the first sublayers, which comprises a pH buffering material for reducing the coat of urinary crystals on the catheter or stent. 42. The method of Appendix 42, comprising applying a second sublayer comprising an antibacterial material covering the portion.

Not only these and other features and properties of the present disclosure, but also the methods of operation and function of the relevant elements of the structure and the economic combination of parts and manufacturing, all of which form part of this specification and are similar. Reference numbers will be more apparent from the discussion of the following description and accompanying appendices, with reference to the accompanying drawings, which specify the corresponding parts in the various figures. However, it should be expressly understood that the drawings are for illustration and illustration purposes only and are not intended as a limitation definition of the invention.

Further features as well as other examples and advantages will be apparent from the embodiments for carrying out the following inventions discussed with reference to the drawings.

FIG. 1A is a schematic representation of an indwelling portion of a system comprising a ureteral stent and a bladder catheter deployed in a patient's urinary tract according to an embodiment of the invention.

FIG. 1B is a schematic representation of an indwelling portion of a system comprising a ureteral catheter and a bladder catheter deployed in the patient's urinary tract according to an embodiment of the present invention.

FIG. 1C is a schematic representation of an indwelling portion of a system comprising a ureteral catheter and a bladder catheter deployed in a patient's urinary tract according to an embodiment of the present invention.

FIG. 1D is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1E is a cross-sectional view of a retention portion of FIG. 1D obtained along line 1E-1E of FIG. 1D according to an embodiment of the present invention.

FIG. 1F is a schematic representation of an indwelling portion of a system comprising a ureteral catheter and a bladder catheter deployed in the patient's urinary tract according to an embodiment of the present invention.

FIG. 1G is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1H is a side elevation view of a retention portion of FIG. 1G according to an embodiment of the present invention.

FIG. 1I is an upper plan view of a retention portion of FIG. 1G according to an embodiment of the present invention.

FIG. 1J is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1K is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1L is a side elevation view of a retention portion of a bladder catheter prior to deployment according to an embodiment of the present invention.

FIG. 1M is a side elevation view of the retention portion of FIG. 1L after deployment according to an embodiment of the present invention.

FIG. 1N is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1O is a cross-sectional view of a part of the retention portion of FIG. 1N according to the embodiment of the present invention.

FIG. 1P is a schematic representation of an indwelling portion of a system comprising a ureteral catheter and a bladder catheter deployed in a patient's urinary tract according to an embodiment of the present invention.

FIG. 1Q is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1R is a cross-sectional view of a part of the retention portion of FIG. 1Q according to the embodiment of the present invention.

FIG. 1S is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1T is a cross-sectional view of a part of the retention portion of FIG. 1S according to the embodiment of the present invention.

FIG. 1U is a schematic representation of an indwelling portion of a system comprising a ureteral catheter and a bladder catheter deployed in a patient's urinary tract according to an embodiment of the present invention.

FIG. 1V is a perspective view of a retention portion of a bladder catheter according to an embodiment of the present invention.

FIG. 1W is a cross-sectional view of a retention portion of FIG. 1V obtained along line 1W-1W of FIG. 1V according to an embodiment of the present invention.

FIG. 2A is a schematic representation of an indwelling portion of a system comprising a ureteral catheter deployed in the patient's urinary tract according to an embodiment of the invention.

FIG. 2B is a schematic representation of an indwelling portion of a system comprising a ureteral catheter deployed in the patient's urinary tract according to an embodiment of the invention.

FIG. 3 is a biaxial perspective view of an example of a prior art deformable ureteral stent according to FIG. 1 of PCT Patent Application Publication No. WO 2017/019974, and the left image shows the uncompressed state of the stent. The image on the right shows the compressed state of the stent.

FIG. 4 is a perspective view of an embodiment of a prior art ureteral stent according to FIG. 4 of US Patent Application Publication No. 2002/0183853A1.

FIG. 5 is a perspective view of an embodiment of a prior art ureteral stent according to FIG. 5 of US Patent Application Publication No. 2002/0183853A1.

FIG. 6 is a perspective view of an embodiment of a prior art ureteral stent according to FIG. 7 of US Patent Application Publication No. 2002/0183853A1.

FIG. 7A is a schematic representation of another embodiment of the indwelling portion of the system comprising a ureteral catheter and a bladder catheter deployed in the patient's urinary tract according to an embodiment of the present invention.

FIG. 7B is a schematic diagram of a system for inducing negative pressure into a patient's urinary tract according to an embodiment of the present invention.

FIG. 7C is a ureter according to the invention located within the renal pelvis region of the kidney, imaginatively showing the general changes that may occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter. It is an enlarged schematic view of a part of a catheter.

FIG. 8A is a perspective view of an exemplary catheter according to an embodiment of the present invention.

FIG. 8B is a front view of the catheter of FIG. 8A.

FIG. 9A is a schematic diagram of an example of a retention portion for a catheter according to an embodiment of the present invention.

FIG. 9B is a schematic representation of another embodiment of the retention portion for a catheter according to an embodiment of the present invention.

FIG. 9C is a schematic representation of another embodiment of the retention portion for a catheter according to an embodiment of the present invention.

FIG. 9D is a schematic representation of another embodiment of the retention portion for a catheter according to an embodiment of the present invention.

FIG. 9E is a schematic representation of another embodiment of the retention portion for a catheter according to an embodiment of the present invention.

FIG. 10 is a front view of another embodiment of the catheter according to the embodiment of the present invention.

FIG. 10A is a perspective view of a retention portion of the catheter of FIG. 10 encapsulated by a circular 10A according to an embodiment of the present invention.

FIG. 10B is a front view of the retention portion of FIG. 10A according to the embodiment of the present invention.

FIG. 10C is a rear view of the retention portion of FIG. 10A according to an embodiment of the present invention.

FIG. 10D is a top view of the retention portion of FIG. 10A according to the embodiment of the present invention.

FIG. 10E is a cross-sectional view of a retention portion of FIG. 10A obtained along lines 10E-10E according to an embodiment of the present invention.

FIG. 10F is a line according to an embodiment of the invention located within the renal pelvis region of the kidney, which generally shows the changes that are likely to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter. It is sectional drawing of the retention part of FIG. 10A obtained along 10E-10E.

FIG. 10G is a line 10E-10E according to an embodiment of the invention positioned in the bladder that generally shows the changes that are likely to occur in the bladder tissue in response to the application of negative pressure through the bladder catheter. It is sectional drawing of the retention part of FIG. 10A obtained along the way.

FIG. 11 is a schematic representation of the retention portion of the catheter in a constrained or linear position according to an embodiment of the invention.

FIG. 12 is a schematic representation of another embodiment of the retention portion of the catheter in a restrained or linear position according to an embodiment of the present invention.

FIG. 13 is a schematic representation of another embodiment of the retention portion of the ureteral catheter in a restrained or linear position according to an embodiment of the present invention.

FIG. 14 is a schematic representation of another embodiment of the retention portion of the catheter in a restrained or linear position according to an embodiment of the present invention.

FIG. 15A is a graph showing the percentage of fluid flow through an exemplary catheter opening as a function of position, according to an embodiment of the invention.

FIG. 15B is a graph showing the percentage of fluid flow through the opening of another exemplary catheter as a function of position, according to an embodiment of the invention.

FIG. 15C is a graph showing the percentage of fluid flow through the opening of another exemplary catheter as a function of position, according to an embodiment of the invention.

FIG. 16 is a schematic diagram of a retention portion of a catheter showing a station for calculating fluid flow coefficients for mass transfer balance assessment according to an embodiment of the present invention.

FIG. 17 is a schematic representation of an indwelling portion of a system comprising a ureteral catheter and a bladder catheter deployed in a patient's urinary tract according to another embodiment of the invention.

FIG. 18A is a side elevation view of the retention portion of the catheter according to an embodiment of the present invention.

FIG. 18B is a cross-sectional view of the retention portion of the catheter of FIG. 18A obtained along line BB of FIG. 18A.

FIG. 18C is an upper plan view of the retention portion of the catheter of FIG. 18A obtained along line CC of FIG. 18A.

FIG. 18D shows urine according to an embodiment of the invention located within the renal pelvis region of the kidney, which generally shows the changes that are likely to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter. It is sectional drawing of the retention part of a ureteral catheter.

FIG. 18E is a retention portion of a bladder catheter according to an embodiment of the invention positioned within the bladder that generally shows the changes that are likely to occur within the bladder tissue in response to the application of negative pressure through the bladder catheter. It is a cross-sectional view of.

FIG. 19 is a side elevation view of a retention portion of another catheter according to an embodiment of the present invention.

FIG. 20 is a side elevation view of a retention portion of another catheter according to an embodiment of the present invention.

FIG. 21 is a side elevation view of a retention portion of another catheter according to an embodiment of the present invention.

FIG. 22A is a perspective view of a retention portion of another ureteral catheter according to an embodiment of the present invention.

22B is an upper plan view of the retention portion of the catheter of FIG. 22A obtained along line 22B-22B of FIG. 22A.

FIG. 23A is a perspective view of a retention portion of another catheter according to an embodiment of the present invention.

FIG. 23B is an upper plan view of the retention portion of the catheter of FIG. 23A obtained along line 23B-23B of FIG. 23A.

FIG. 24A is a perspective view of a retention portion of another catheter according to an embodiment of the present invention.

FIG. 24B shows urine according to an embodiment of the invention located within the renal pelvis region of the kidney, which generally shows the changes that are likely to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter. It is sectional drawing of the retention part of a ureteral catheter.

FIG. 24C is a retention portion of a bladder catheter according to an embodiment of the invention positioned within the bladder that generally shows the changes that are likely to occur within the bladder tissue in response to the application of negative pressure through the bladder catheter. It is a cross-sectional view of.

FIG. 25 is a side elevation view of a retention portion of another catheter according to an embodiment of the present invention.

FIG. 26 is a side elevation view of a retention portion of another catheter according to an embodiment of the present invention.

FIG. 27 is a cross-sectional side view of a retention portion of another catheter according to an embodiment of the present invention.

FIG. 28A is a perspective view of a retention portion of another catheter according to an embodiment of the present invention.

28B is an upper plan view of the retention portion of the catheter of FIG. 28A.

FIG. 29A is a perspective view of a retention portion of another catheter according to an embodiment of the present invention.

29B is an upper plan view of the retention portion of the catheter of FIG. 29A.

FIG. 29C shows urine according to an embodiment of the invention located within the renal pelvis region of the kidney, which generally shows the changes that are likely to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter. It is sectional drawing of the retention part of a ureteral catheter.

FIG. 30 is a perspective view of a retention portion of another catheter according to an embodiment of the present invention.

FIG. 31 is an upper plan view of the retention portion of the catheter of FIG.

FIG. 32A is a perspective view of a retention portion of another catheter according to an embodiment of the present invention.

32B is an upper plan view of the retention portion of the catheter of FIG. 32A.

FIG. 33 is a cross-sectional side elevation view of a retaining portion of another catheter according to an embodiment of the present invention.

FIG. 34 is a cross-sectional side elevation view of a retaining portion of another catheter according to an embodiment of the present invention.

FIG. 35A is a perspective view of a retention portion of another catheter according to an embodiment of the present invention.

35B is a cross-sectional side elevation view of the retention portion of the catheter of FIG. 35A obtained along line BB of FIG. 35A.

FIG. 36 is a side elevation view showing a cut sectional view of a sheath surrounding a catheter according to an embodiment of the present invention in a contracted configuration for insertion into a patient's ureter.

FIG. 37A is a schematic representation of another embodiment of the retention portion for a catheter according to an embodiment of the present invention.

FIG. 37B is a schematic cross-sectional view of a portion of the retention portion of FIG. 37A obtained along line BB of FIG. 37A.

FIG. 38A is a schematic representation of another embodiment of the retention portion for a catheter according to an embodiment of the present invention.

FIG. 38B is a schematic cross-sectional view of a portion of the retention portion of FIG. 5A obtained along line BB of FIG. 38A.

FIG. 39A is a schematic representation of another embodiment of the retention portion for a catheter according to an embodiment of the present invention.

FIG. 39B shows urine according to an embodiment of the invention located within the renal pelvis region of the kidney, which generally shows the changes that are likely to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter. FIG. 3 is a schematic cross-sectional view of another embodiment of a retention portion for a ureteral catheter.

FIG. 39C is for a bladder catheter according to an embodiment of the invention positioned within the bladder that generally shows the changes that are likely to occur within the bladder tissue in response to the application of negative pressure through the bladder catheter. It is the schematic of the cross-sectional view of another embodiment of the retention part.

FIG. 40A is a schematic cross-sectional view of another embodiment of the retention portion for a catheter according to an embodiment of the present invention.

FIG. 40B shows urine according to an embodiment of the invention located within the renal pelvis region of the kidney, which generally shows the changes that are likely to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter. FIG. 3 is a schematic cross-sectional view of another embodiment of a retention portion for a ureteral catheter.

FIG. 40C is for a bladder catheter according to an embodiment of the invention positioned within the bladder that generally shows the changes that are likely to occur within the bladder tissue in response to the application of negative pressure through the bladder catheter. It is the schematic of the cross-sectional view of another embodiment of the retention part.

FIG. 41A is a schematic representation of another embodiment of the retention portion for a catheter according to an embodiment of the present invention.

FIG. 41B shows urine according to an embodiment of the invention located within the renal pelvis region of the kidney, which generally shows the changes that are likely to occur within the renal pelvis tissue in response to the application of negative pressure through the ureteral catheter. FIG. 3 is a schematic cross-sectional view of another embodiment of a retention portion for a ureteral catheter.

FIG. 41C is for a bladder catheter according to an embodiment of the invention positioned within the bladder that generally shows the changes that are likely to occur within the bladder tissue in response to the application of negative pressure through the bladder catheter. It is the schematic of the cross-sectional view of another embodiment of the retention part.

FIG. 42A is a flow chart illustrating a process for inserting and deploying a system according to an embodiment of the present invention.

FIG. 42B is a flow chart illustrating a process for applying a negative pressure using a system according to an embodiment of the present invention.

FIG. 43 is a schematic diagram of the renal unit and surrounding vasculature showing the location of the capillary bed and tubular tubules.

FIG. 44 is a schematic diagram of a system for inducing negative pressure in a patient's urinary tract according to an embodiment of the present invention.

45A is a plan view of a pump for use with the system of FIG. 44 according to an embodiment of the present invention.

45B is a side elevation view of the pump of FIG. 45A.

FIG. 46 is a schematic diagram of an experimental setup for evaluating negative pressure therapy in a porcine model according to an embodiment of the invention.

FIG. 47 is a graph of creatinine clearance rates for tests performed using the experimental settings shown in FIG.

FIG. 48A is a low magnification photomicrograph of kidney tissue from a stagnant kidney treated with negative pressure therapy.

FIG. 48B is a high magnification light micrograph of the kidney tissue shown in FIG. 48A.

FIG. 48C is a low magnification light micrograph of kidney tissue from stasis and untreated (eg, control) kidneys.

FIG. 48D is a high magnification light micrograph of the kidney tissue shown in FIG. 23C.

FIG. 49 is a flow chart illustrating a process for reducing creatinine and / or protein levels in a patient according to an embodiment of the invention.

FIG. 50 is a flow chart illustrating a process for treating a patient receiving a resuscitation infusion according to an embodiment of the present invention.

FIG. 51 is a graph of serum albumin relative to baseline for tests performed in pigs using the experimental methods described herein.

FIG. 52A is a perspective view of a ureteral catheter comprising a multifunctional coating according to certain aspects of the invention.

52B is a side view of the catheter of FIG. 52A.

FIG. 53 is a cross-sectional view of a portion of the ureteral catheter of FIG. 52A in a linear, non-coiled state.

FIG. 54 is a cross-sectional view of a portion of the ureteral catheter of FIG. 52A in the unfolded or coiled state.

FIG. 55 is a flow chart of a method of manufacture for a coated ureteral catheter according to one aspect of the present disclosure.

FIG. 56 is a cross-sectional view of a portion of a ureteral catheter in a linear, non-coiled state, comprising another exemplary multifunctional coating, according to one aspect of the present disclosure.

FIG. 57 is a cross-sectional view of a portion of a ureteral catheter in a linear, non-coiled state, comprising another exemplary multifunctional coating, according to one aspect of the present disclosure.

As used herein, the singular forms of "a," "an," and "the" also include plural references unless explicitly indicated otherwise by context.

As used herein, the terms "right", "left", "top", and variants thereof shall be relevant to the invention as oriented in the drawings. The term "proximal" refers to the portion of the catheter device that is operated or contacted by the user and / or the portion of the indwelling catheter closest to the urinary tract access site. The term "distal" refers to a portion of a device that is inserted at the opposite end of a catheter device that is configured to be inserted into a patient and / or at the most distal end of the patient's urinary tract. However, it should be understood that the present invention can take various alternative orientations and therefore such terms are not considered limiting. It should also be understood that the present invention may take various alternative variants and step sequences, unless the opposite is explicitly specified. It should also be understood that the specific devices and processes illustrated in the accompanying drawings and described in the following specification are examples. Therefore, the specific dimensions and other physical properties associated with the embodiments disclosed herein are not considered limiting.

For the purposes of this specification, unless otherwise indicated, all numbers representing quantities such as components, reaction states, dimensions, physical properties, etc. used in the specification and claims are in all cases the term ". Please be understood as being modified by "about". Unless the opposite is indicated, the numerical parameters described in the following specification and the accompanying claims are approximations that may vary depending on the desired properties sought to be obtained by the present invention.

The numerical ranges and parameters that describe the broad scope of the invention are approximations, but the numerical values described in the specific examples are reported as precisely as possible. However, any numerical value essentially contains some error that inevitably arises from the standard deviation found in that individual test measurement.

It should also be understood that any numerical range listed herein is intended to include all subranges contained therein. For example, the range "1-10" starts from any range in between, including 1 listed minimum and 10 listed maximum, i.e. a minimum equal to or greater than 1. Includes all subranges ending with a maximum value equal to or less than, and all subranges in between, such as 1 to 6.3, or 5.5 to 10, or 2.7 to 6.1. Is intended.

As used herein, the terms "communicate" and "communicate" refer to the reception or transfer of one or more signals, messages, commands, or other types of data. When one unit or component communicates with another unit or component, one unit or component receives data directly or indirectly from another unit or component, and / or there. It means that it is possible to transmit data. This can refer to a direct or indirect connection, which in nature can be wired and / or wireless. In addition, the two units or components are mutually even if the data transmitted is modified, processed, routed, and equivalent between the first and second units or components. Can communicate with. For example, the first unit can communicate with the second unit even if the first unit passively receives the data and does not actively transmit the data to the second unit. As another embodiment, the first unit may communicate with the second unit even if the intermediate unit processes data from one unit and transmits the processed data to the second unit. can. It should be understood that many other sequences are also possible.

As used herein, "maintaining the patency of fluid flow between the patient's kidney and bladder" is from the kidney through the ureter, ureteral stent, and / or ureteral catheter. It means establishing, increasing, or maintaining the flow of fluids such as urine to the bladder as well as to the outside of the body. In some embodiments, fluid flow is facilitated by providing a protective surface area 1001 within the upper urinary tract and / or bladder and preventing the urinary endothelium from contracting or crushing into the fluid column or flow. Or be maintained. As used herein, "fluid" means urine from the urinary tract and any other fluid.

As used herein, "negative pressure" refers to the pressure applied to the proximal end of the bladder catheter or the proximal end of the urinary catheter, respectively, prior to the application of negative pressure to the bladder, respectively. Below the existing pressure at the proximal end of the catheter or the proximal end of the urinary catheter, eg, the proximal end of the bladder catheter or the proximal end of the urinary catheter, and prior to the application of negative pressure, respectively. , Means that there is a pressure difference with the existing pressure at the proximal end of the bladder catheter or the proximal end of the urinary tract catheter. This pressure difference causes fluid from the kidney to be drawn into the ureteral or bladder catheter, or through both the ureteral and bladder catheters, respectively, and then to the outside of the patient's body. For example, the negative pressure applied to the proximal end of the bladder catheter or the proximal end of the urinary catheter is less than atmospheric pressure (about 760 mmHg or less than about 1 atmosphere) so that the fluid is drawn from the kidney and / or the bladder. Alternatively, it may be less than the pressure measured at the proximal end of the bladder catheter or the proximal end of the urinary catheter prior to application of negative pressure. In some embodiments, the negative pressure applied to the proximal end of the bladder catheter or the proximal end of the ureteral catheter is from about 0.1 mmHg to about 150 mmHg, or from about 0.1 mmHg to about 50 mmHg, or about 0. It can range from 1 mmHg to about 10 mmHg, or from about 5 mmHg to about 20 mmHg, or about 45 mmHg (gauge pressure in pump 710 or gauge pressure in negative pressure source). In some embodiments, the negative pressure source is equipped with a pump outside the patient's body for the application of negative pressure through both the bladder and urinary catheters, which in turn draws fluid from the kidneys. In the urinary catheter, both the urinary catheter and the bladder catheter are passed and then pulled out of the patient's body. In some embodiments, the negative pressure source comprises a vacuum source outside the patient's body for application and regulation of negative pressure through both the bladder and urinary catheters, which in turn, from the kidney. Fluid is drawn into the urinary catheter, through both the urinary catheter and the bladder catheter, and then to the outside of the patient's body. In some embodiments, the vacuum source is selected from the group consisting of a wall suction source, a vacuum bottle, and a manual vacuum source, or the vacuum source is provided by a pressure differential. In some embodiments, the negative pressure received from the negative pressure source can be controlled manually, automatically, or in combination thereof. In some embodiments, a controller is used to adjust the negative pressure from the negative pressure source. Non-limiting examples of negative and positive pressure sources are discussed in detail below.

As used herein, "positive pressure" refers to the pressure applied to the proximal end of the bladder catheter or the proximal end of the urinary catheter, respectively, prior to the application of negative pressure to the bladder, respectively. Over the existing pressure at the proximal end of the catheter or the proximal end of the urinary catheter, fluid present in the urinary or bladder catheter or through both the urinary and bladder catheters into the bladder or kidney, respectively. It means to flow back toward. In some embodiments, the positive pressure applied to the proximal end of the bladder catheter or the proximal end of the ureteral catheter is from about 0.1 mmHg to about 150 mmHg, or from about 0.1 mmHg to about 50 mmHg, or about 0. It can range from 1 mmHg to about 10 mmHg, or from about 5 mmHg to about 20 mmHg, or about 45 mmHg (gauge pressure in pump 710 or gauge pressure in positive pressure source). The positive pressure source can be provided, for example, by a pump or wall pressure source, or a pressurized bottle, and can be controlled manually, automatically, or in combination thereof. In some embodiments, a controller is used to adjust the positive pressure from the positive pressure source.

Fluid retention and venous stasis are major problems in the progression of progressive renal disease. Excess sodium intake associated with a relative decrease in excretion leads to isotonic volume expansion and complications of secondary compartment syndrome. In some examples, the invention generally relates to devices and methods for facilitating the excretion of urine or waste from a patient's bladder, ureter, and / or kidney. In some examples, the invention generally relates to a system and method for inducing negative pressure in a patient's bladder, ureter, and / or kidney, eg, at least part of the urinary system. Although not intended to be constrained by any theory, applying negative pressure to the bladder, ureters, and / or kidneys, eg, at least part of the urinary system, is sodium in some situations. And the medullary renal unit of water may compensate for tubular reabsorption. Compensation for sodium and water reabsorption can increase urine production, reduce total body sodium, and improve erythrocyte production. Target removal of excess sodium makes it possible to maintain fluid loss, as intramedullary pressure is driven by sodium, and thus volume overload. Removal of fluid volume restores medulla stasis. Normal urine production is 1.48 to 1.96 L / day (or 1 to 1.4 ml / min).

Fluid retention and venous stasis are also major problems in the progression of prerenal acute kidney injury (AKI). Specifically, AKI may be associated with perfusion through the kidney or loss of blood flow. Therefore, in some examples, the invention promotes improved renal hemodynamics and increases urination for the purpose of alleviating or reducing venous stasis. In addition, treatment and / or inhibition of AKI is expected to have a positive effect on the development of other conditions and / or reduce it, with, for example, NYHA classification III and / or classification IV heart failure. This includes reducing or preventing deterioration of renal function in patients. Different levels of heart failure are classified by The Criteria Committee of the New York Heart Association, (1994), Nomenclature and Criteria for Bostonesissoses pp. 253-256, the disclosure of which is incorporated herein by reference in its entirety. Reducing or blocking episodes of AKI and / or chronic perfusion reduction can also be treatment for stage 4 and / or stage 5 chronic kidney disease. The progression of chronic kidney disease is described in the National Kidney Foundation, K / DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evolution, Classication and Tratification. Am. J. Kidney Dis. 39: S1-S266,2002 (Suppl. 1), the disclosure of which is incorporated herein by reference in its entirety.

Also disclosed herein are ureteral catheters, ureteral stents, and / or bladder catheters that are useful for preventing, delaying, and / or treating end-stage renal disease (“ESRD”). Can be. The average dialysis patient spends about $ 90,000 a year on medical use for a total cost of $ 33.9 billion for the US government. Currently, ESRD patients account for more than 13% of total spending, including only 2.9% of all Medicare beneficiaries. Incidence and cost per patient have been stable in recent years, but the volume of active patients continues to rise.

The five stages of progressive chronic kidney disease (“CKD”) are based on glomerular filtration rate (GFR). Patients in stage 1 (GFR> 90) have normal filtration, while stage 5 (GFR <15) has renal failure. As with many chronic diseases, diagnostic capture improves with increasing symptoms and disease severity.

The CKD3b / 4 subgroup is a smaller subgroup that reflects significant changes in disease progression, healthcare system involvement, and transition to ESRD. Emergency department care increases with the severity of CKD. Within the US Veterans Affairs Department group, nearly 86% of incidental dialysis patients were hospitalized within five years prior to hospitalization. Of them, 63% were hospitalized at the start of dialysis. This suggests a tremendous opportunity to intervene prior to dialysis.

Despite tracing further down the arterial tree than other organs, the kidneys receive an imbalanced amount of cardiac output at rest. The glomerular membrane represents the path of minimum resistance of the filtrate into the renal tubules. In a healthy state, the renal unit has multiple complex and redundant means of self-regulation within the normal range of arterial pressure.

Vein stasis is involved in reduced renal function and is associated with systemic hypercirculatory blood flow found in late-stage CKD. Because the kidney is covered with a semi-rigid capsule, small changes in venous pressure are converted into direct changes in tubular pressure. This shift in tubular pressure has been shown to upregulate sodium and water reabsorption and perpetuate the vicious circle.

More progressive CKD, regardless of initial invasiveness and early progression, is associated with reduced filtration (by definition) and further hypernitrogenemia. Regardless of whether the remaining renal units are overabsorbing water or simply not being able to filter adequately, this renal unit loss is associated with fluid retention and progressive decline in renal function.

The kidney is sensitive to subtle volume shifts. As the pressure in either the tubular or capillary bed increases, the pressure in the other follows. As capillary bed pressure rises, filtration fluid production and urine elimination can decrease dramatically. Although not intended to be constrained by any theory, it is believed that the slight and regulated negative pressure delivered to the renal pelvis reduces pressure between each of the functioning renal units. In a healthy biological structure, the renal pelvis is connected to about 1 million individual renal units via the calyx and collecting duct network. Each of these renal units is essentially a fluid column that connects Bowman's capsule to the renal pelvis. The pressure transmitted to the renal pelvis translates throughout. As negative pressure is applied to the renal pelvis, glomerular capillary pressure is thought to push more filtrate across the glomerular membrane, leading to increased urination.

It is important to note that the tissue of the urinary tract is covered with urinary epithelium, a type of transitional epithelium. The inner tissue layer inside the urinary tract is also referred to as the ureteral or urothelial tissue, such as the mucosal tissue 1003 of the ureter and / or kidney and bladder tissue 1004. The urothelium has a very high elasticity, allowing a significant range of crushing and extensibility. The urothelium covering the ureteral lumen is first surrounded by a lamina propria, a thin layer of loose connective tissue, both containing the urothelial mucosa. The mucosa is then surrounded by a layer of longitudinal muscle fibers. The elasticity of these longitudinal muscle fibers surrounding the urothelial mucosa and the urothelial mucosa itself allows the ureter to relax in a crushed stellate section and then expand to full swelling during diuresis. The tissue structure of any normal ureteral cross section generally reveals the stellate lumen in humans and other mammals used in bridging medical research. Wolf et al. , “Comparative Ureteral Microanatomy”, JEU 10: 527-31 (1996).

The process of transporting urine from the kidneys to the bladder is facilitated by contractions through the renal pelvis and peristalsis through the rest of the ureter distally. The renal pelvis is an enlargement of the proximal ureter into a funnel shape, where the ureter enters the kidney. The renal pelvis has been shown to be a continuation of the ureter, in fact consisting of the same tissue, but with one additional muscle layer that allows it to contract. Dixon and Gosling, "The Musculature of the Human Renal Calyces, Pelvis and Upper Uter", J. Mol. Anat. 135: 129-37 (1982). These contractions push urine through the renal pelvis funnel, allowing peristaltic waves to propagate through the ureter to the bladder.

Imaging studies have shown that the canine ureter can easily increase up to 17 times its resting cross-sectional area and contain large amounts of urine during diuresis. Woodburne and Lapides, "The Ureteral Lumen During Peristalsis", AJA 133: 255-8 (1972). Among the pigs considered to be the closest animal models for the human upper ureter, the renal pelvis and recent ureters have, in fact, been shown to be the most flexible of all ureteral segments. Gregersen, et al. , "Regional Differenses Exist in Elastic Wall Properties in the Printer", SJUN 30: 343-8 (1996). Various studies with human ureteral microbiological structures Wolf comparison studies of animal ones show that the thickness of the lamina propria relative to the entire ureteral diameter in dogs (29.5% in humans and 34% in dogs), and A comparable ratio of smooth muscle to total muscle cross-sectional area in pigs (54% in humans and 45% in pigs) was revealed. Certainly, there are limits to comparisons between species, but dogs and pigs have become a strong focus in the study and understanding of human ureteral biostructure and physiology, and these references are high. Support the level of translatability.

There is much more data available in the structure and mechanics of the porcine and dog ureters as well as the renal pelvis than the human ureters. This is in part to attempt to clinically accurately identify the invasiveness required for such detailed analysis, as well as the size and composition of such small flexible dynamic structures. Due to the inherent limitations of various diagnostic imaging methods (MRI, CT, ultrasound, etc.). Nevertheless, this ability for the renal pelvis to swell or completely crush in humans is an obstacle for nephrologists and urologists seeking to improve urinary flow.

Although not intended to be constrained by any theory, we find that the application of negative pressure can help facilitate fluid flow from the kidney, causing peripheral tissue to flow into the fluid column under negative pressure. A very specific tool designed to develop a protective surface area to open or maintain openness inside the renal pelvis while preventing it from contracting or crushing is the application of negative pressure within the renal pelvis. Theorized what is needed to promote. The catheter design of the invention disclosed herein provides a protective surface area and prevents the surrounding urothelial tissue from contracting or crushing the fluid column under negative pressure. The catheter design of the invention disclosed herein can maintain normal stellate longitudinal folding of the ureteral wall away from the central axis of the catheter drain lumen and the protected hole, by peristaltic waves. It is believed that it may prevent spontaneous sliding and / or downward movement of the catheter following the stellate cross-sectional area of the ureteral lumen.

Also, the catheter design of the invention disclosed herein can avoid unprotected open holes at the distal end of the drainage lumen, which cannot protect surrounding tissue during aspiration. Although it is convenient to think of the ureter as a straight tube, the true ureter and renal pelvis can enter the kidney at various angles. Lippincot Williams & Wilkins, Anals of Surgery, 58, Figures 3 & 9 (1913). Therefore, when deploying such a catheter within the renal pelvis, it may be difficult to control the orientation of the unprotected open hole at the distal end of the drainage lumen. This single hole does not have a means of ensuring either reliable or consistent distance from the tissue wall, thereby allowing the tissue to block the unprotected open hole. And can present a local suction point, at risk of tissue damage. Also, the catheter design of the invention disclosed herein provides an unprotected open hole at the distal end of the drainage lumen near the kidney, which can result in suction and / or occlusion of the calyx. It is possible to avoid the installation of the balloon. Placement of a balloon with an unprotected open hole at the distal end of the drainage lumen at the base of the ureter-renal pelvis junction can result in suction to the renal pelvis tissue and obstruction by the renal pelvis tissue. Also, a rounded balloon may indicate a risk of ureteral detachment or other damage from incidental traction on the balloon.

The step of delivering negative pressure into the patient's kidney area has several anatomical challenges for at least three reasons. First, the urinary system consists of highly flexible tissue that is easily deformed. Medical books often describe the bladder as a thick muscular structure that can remain fixed, regardless of the volume of urine contained in the bladder. However, in reality, the bladder is a soft deformable structure. The bladder contracts and conforms to the volume of urine contained within the bladder. An empty bladder is more like a contracted latex balloon than a ball. In addition, the inner mucosal layer inside the bladder is soft and susceptible to inflammation and damage. It is desirable to avoid drawing urinary tissue into the orifice of the catheter, through which it maintains proper fluid flow and avoids injury to surrounding tissue.

Second, the ureter is a small tubular structure that can expand and contract and transport urine from the renal pelvis to the bladder. This transport occurs in two ways: peristaltic activity and pressure gradients within the open system. In peristaltic activity, the urinary part is pushed before the contractile wave, which almost completely occludes the lumen. The wave pattern begins within the renal pelvis area, propagates along the ureter, and terminates at the bladder. Such complete occlusion can interrupt fluid flow and prevent the negative pressure delivered within the bladder from reaching the renal pelvis without assistance. A second type of transport, due to a pressure gradient through a wide open ureter, can be present during large volumes of urine flow. During such a period of mass urine production, the pressure head in the renal pelvis may not need to be caused by the contraction of the smooth muscles of the upper urinary tract, but rather it is caused by the anterior flow of urine and therefore. Reflects arterial blood pressure. Kiil F. , "Urinary Flow and Ureteral Peristalsis" in: Lutzeyer W. et al. , Melchior H. (Eds) Urodynamics. Springer, Berlin, Heidelberg (pp. 57-70) (1973).

Third, the renal pelvis is at least as flexible as the bladder. The thin wall of the renal pelvis can be expanded to accommodate a normal volume multiple times, as it occurs, for example, in patients with hydronephrosis.

More recently, the use of negative pressure in the renal pelvis to remove thrombi from the renal pelvis by the use of suction has been warned by the inevitable crushing of the renal pelvis, thus preventing the use of negative pressure in the renal pelvis region. Webb, Percutaneous Renal Surgery: A Practical Clinical Handbook. p 92. Springer (2016).

Although not intended to be constrained by any theory, the renal pelvis and bladder tissues are flexible enough to be pulled inward during the delivery of negative pressure and deliver negative pressure. Conform to the shape and volume of the tool used to. Similar to the vacuum seal of the corn ears with shells, the urothelial tissue will be crushed and conformal to it around the negative pressure source. To prevent tissue from obstructing the lumen and obstructing the flow of urine, we have obstructed a protective surface area sufficient to maintain the fluid column when a slight negative pressure is applied. Theorized that it would prevent or prevent.

We have determined that there are specific features that allow the catheter tool to be successfully deployed within the urinary region not described above and to deliver negative pressure through it. These require a deep understanding of the biological structure and physiology of the treatment zone and adjacent tissues. The catheter provides a protective surface area within the renal pelvis by supporting the urothelium and preventing the urothelial tissue from occluding the opening in the catheter during the application of negative pressure through the catheter lumen. There must be. For example, establishing a three-dimensional shape or void volume with no or essentially no urothelial tissue opens a fluid column or flow from each of the million renal units into the drainage lumen of the catheter. Ensure existence.

Since the renal pelvis consists of vertically oriented smooth muscle cells, the protected surface area would ideally incorporate a multiplanar approach to establishing a protected surface area. Biological structures are often three planes: sagittal (vertical front-to-posterior dividing the body into right and left parts), coronal (vertical left and right dividing the body into the back and abdomen), and transverse. Described in the plane (horizontal or axial, which divides the body into upper and lower parts and is perpendicular to the sagittal and coronal planes). Smooth muscle cells in the renal pelvis are vertically oriented. It is desirable that the catheter also maintain radial surface area across many cross-sections between the kidney and the ureter. This allows the catheter to occupy both the longitudinal and horizontal portions of the renal pelvis in establishing a protective surface area of 1001. In addition, given the flexibility of the tissue, protection of these tissues from openings or orifices leading to the lumen of the catheter tool is desirable. The catheters discussed herein can be useful for delivering negative pressure, positive pressure, or can be used at ambient pressure, or any combination thereof.

In some embodiments, a deployable / retractable dilation mechanism is utilized that, when deployed, creates and / or maintains a patent fluid column or flow between the kidney and the catheter drainage lumen. Ru. This deployable / retractable mechanism, when deployed, supports the urothelium and prevents urothelial tissue from occluding the opening in the catheter during the application of negative pressure through the catheter lumen. This creates a protective surface area 1001 in the renal pelvis. In some embodiments, the retention portion is configured to extend to a deployment position where the diameter of the retention portion exceeds the diameter of the drainage lumen portion.

Referring to FIGS. 1A-1C, 1F, 1P, 1U, 2A, 2B, 7A, 7B, 17, and 44, generally the urinary tract shown in 1 comprises the patient's right kidney 2 and left kidney 4. As discussed above, kidneys 2 and 4 are involved in hemofiltration and clearance of waste compounds from the body through urine. The urine produced by the right kidney 2 and the left kidney 4 is drained into the patient's bladder 10 through the renal tubules, i.e. the right ureter 6 and the left ureter 8. For example, urine can be conducted through ureters 6 and 8 by peristalsis of the ureteral wall and by gravity. The ureters 6 and 8 enter the bladder 10 through the ureteral ostium or opening 16. The bladder 10 is a flexible and substantially hollow structure adapted to collect urine until it is excreted from the body. The bladder 10 is capable of transitioning from an empty position (indicated by reference line E) to a full position (indicated by reference line F). When the bladder is in vacant position E, the bladder upper wall 70 is, for example, a mesh 57 in FIGS. 1A and 1B, a coil 1210 in FIGS. 1C, 1U, and 7A, and a basket of bladder upper wall support 210 in FIG. 1F. Positioned adjacent to the lateral margin 72, 1002 or protective surface area 1001 of the distal end 136 of the bladder catheters 56, 116, as a shaped structure or support cap 212, as an annular balloon 310 in FIG. 1P and as a funnel 116 in FIG. And / or can be homomorphized into it. Normally, when the bladder 10 reaches a substantially full state, urine can be drained from the bladder 10 to the urethra 12 through the urethral sphincter muscle or opening 18 located in the lower portion of the bladder 10. The contraction of the bladder 10 may respond to the stress and pressure applied to the triangular region 14 of the bladder 10, which is the triangular region extending between the ureteral opening 16 and the urethral opening 18. The triangular region 14 is sensitive to stress and pressure so that the pressure on the triangular region 14 increases as the bladder 10 begins to fill. Beyond the threshold pressure on the triangular region 14, the bladder 10 begins to contract and drains the collected urine through the urethra 12.

Similarly, as shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, and 2B, for example, the outer peripheral edges 72, 1002 or protective surface area 1001 of the ureteral catheters 112, 114 of the present invention are urine. The ureter and / or kidney tissue 1003 can be supported and the patency of fluid flow between the patient's kidney and bladder can be maintained.

In some embodiments, for example, the methods and systems 50, 100 as shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7, 17, and 44 are fluid (urinary) from the patient. Etc.) provided to remove the urinary bladder stents 52, 54 (shown in FIG. 1A) or urinary catheters 112, 114 (FIGS. 1B, 1C, 1F, 1P, 1U, 2A, 2B, etc.). Steps to deploy (shown in 7, 17 and 44) into the patient's urinary tracts 6 and 8 to maintain patency of fluid flow between the patient's kidneys 2 and 4 and the bladder 10. Alternatively, in the step of deploying the bladder catheters 56, 116 into the patient's bladder 10, the bladder catheters 56, 116 have a distal end 136 and a proximal end configured to be positioned within the patient's bladder 10. A step and a negative pressure are applied to the proximal ends 117 of the bladder catheters 56, 116 and / or the urinary catheters 112, 114, comprising a drainage lumen portion 140 having 117 and a side wall 119 extending between them. It involves the steps of inducing negative pressure within a portion of the patient's urinary tract and removing fluid from the patient. In some embodiments, the method further deploys a second ureteral stent or second ureteral catheter into the patient's second ureter or kidney, FIGS. 1A, 1B, 1C, 1F, As shown in 1P, 1U, 2A, 2B, 7, 17, and 44, it comprises the step of maintaining the patency of the fluid flow between the patient's second kidney and the bladder. Specific properties of the exemplary ureteral stent or ureteral catheter of the invention are described in detail below.

In some non-limiting examples, ureteral or bladder catheters 56, 112, 114, 116, 312, 412, 512, 812, 1212, 5000, 5001 are (a) proximal portions 117, 128, 1228, It comprises 5006, 5007, 5017 and (b) distal portions 118, 318, 1218, 5004, 5005, the distal portion having at least one protected drain, port, or perforation 133, 533, 1233. In response to the application of negative pressure through the catheter, the ureteral epithelial tissue, such as the mucosal tissue 1003 of the ureter and / or the kidney and bladder tissue 1004, has at least one protected drain, port, or perforation 133. , 533, 1233, retention portions 130, 330, 410, 500, 1230, 1330, 2230, 3230, 4230, 5012, configured to establish an outer peripheral edge 1002 or a protective surface surface 1001 that prevents obstruction. 5013 is provided.
Exemplary ureteral catheters:

Examples of the system 100 are illustrated, including ureteral catheters 112, 114, configured to be located in the patient's urinary tract, as shown in FIGS. 2A, 7, 17, and 44. For example, the distal ends 120, 121, 1220, 5019, 5021 of the ureteral catheters 112, 114 are of the renal pelvis 20, 21 area of the patient's ureters 2, 4, kidneys 6, 8 or kidneys 6, 8. It can be configured to be deployed within at least one.

In some examples, suitable urinary catheters are U.S. Patent No. 9,744,331, U.S. Patent Application Publication No. US2017 / 0021128A1, U.S. Patent Application No. 15 / 687,064, and U.S. Patent Application. 15 / 687,083 (each incorporated herein by reference).

In some embodiments, the system 100 is a first catheter 112 placed within or adjacent to the renal pelvis 20 of the right kidney 2 and a second catheter placed within or adjacent to the renal pelvis 21 of the left kidney 4. Two separate ureteral catheters, such as the catheter 114 of the. The catheters 112, 114 can be separate with respect to their overall length, or are held in close proximity to each other by clips, rings, clamps, or other types of connecting mechanisms (eg, connectors), and the catheters 112, 114. Can facilitate the placement or removal of. As shown in FIGS. 2A, 7, 17, 27, and 44, the proximal ends 113, 115 of each catheter 112, 114 are in the bladder 10 or in the bladder 10 to drain fluid or urine into the bladder. Located at the proximal end of the ureter in the vicinity of. In some embodiments, the proximal ends 113, 115 of each catheter 112, 114 can communicate fluidly with the distal portion or end 136 of the bladder catheters 56, 116. In some embodiments, the catheters 112, 114 can be fused or connected together in the bladder to form a single drainage lumen that drains into the bladder 10.

As shown in FIG. 2A, in some embodiments, one or both proximal ends 113, 115 of the catheters 112, 114 are located within the urethra 12 and optionally fluid to the outside of the patient's body. It can be connected to additional drainage pipes for drainage. As shown in FIG. 2B, in some embodiments, the proximal ends 113, 115 of one or both of the catheters 112, 114 may be positioned to extend from the urethra 12 to the outside of the patient's body. can.

In another embodiment, the catheter 112, 114 is inserted through or encapsulated in another catheter, tube, or sheath along a portion or compartment thereof, and the catheter 112, 114 is inserted into the patient's body. And can facilitate a retreat from it. For example, the bladder catheter 116 is inserted over and / or along the same guide wire as the ureteral catheters 112, 114, or into the same tube used to insert the ureteral catheters 112, 114. Can be done.

Referring to FIGS. 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7, 8A, and 8B, the exemplary ureteral catheters 112, 1212, 5000 have at least one extension body or tube 122, 1222, 5009. It can be provided, the interior of which defines or comprises one or more drainage channels or lumens such as drainage lumens 124, 1224, 5002 and the like. Tubes 122, 1222, 5009 sizes can range from about 1 Fr to about 9 Fr (French catheter scale). In some embodiments, the tubes 122, 1222, 5009 can have an outer diameter ranging from about 0.33 to about 3 mm and an inner diameter ranging from about 0.165 to about 2.39 mm. In one embodiment, the tube 122 is 6 Fr and has an outer diameter of 2.0 ± 0.1 mm. The length of the tubes 122, 1222, 5009 can range from about 30 cm to about 120 cm, depending on the age (eg, child or adult) and gender of the patient.

Tubes 122, 1222, 5009 are made of flexible and / or deformable material, and advance and advance of tubes 122, 1222, 5009 within the bladder 10 and ureters 6, 8 (shown in FIGS. 2 and 7). / Or can promote positioning. The catheter material should be flexible and soft enough to avoid or reduce inflammation of the renal pelvis and ureter, but the renal pelvis or other parts of the ureter exert pressure on the outside of the tubes 122, 1222, 5009. When applied to, or when the renal pelvis and / or ureter is towed against the tubes 122, 1222, 5009 during the induction of negative pressure, the tubes 122, 1222, 5009 are sufficiently rigid to prevent crushing. Should be. For example, tubes 122, 1222, 5009 or drainage cavities are at least partially copper, silver, gold, nickel-titanium alloys, stainless steel, titanium, and / or biocompatible polymers, polyurethanes, polyvinyl chlorides, polys. Tetrafluoroethylene (PTFE), latex, silicon coated latex, silicone, polyglycolide or poly (glycolic acid) (PGA), polylactic acid (PLA), poly (lactic acid-co-glycolic acid), polyhydroxyalkanoic acid, It can be formed from one or more materials, including polycaprolactone and / or a polymer such as poly (propylene fumarate). In one embodiment, the tubes 122, 1222, 5009 are made of thermoplastic polyurethane. Tubes 122, 1222, 5009 may also contain or be impregnated with one or more of copper, silver, gold, nickel-titanium alloys, stainless steel, and titanium. In some embodiments, the tubes 122, 1222, 5009 are impregnated with or formed from a material visible by fluoroscopic imaging. For example, the biocompatible polymer forming tubes 122, 1222, 5009 can be impregnated with barium sulphate or similar radiodensity material. Therefore, the structure and position of tubes 122, 1222, 5009 are visible to fluorescence perspective.

In some embodiments, for example, as shown in FIG. 8B, the tube 122 is a tube 122 configured to be located within the distal portion 118 (eg, ureters 6, 8 and renal pelvis 20, 21). Part) and the central part 126 (eg, part of the tube 122 configured to extend from the distal part 118 through the ureteral opening 16 into the patient's bladder 10 and urethra 12). A portion 128 (eg, a portion of a tube 122 that extends into the bladder 10 or urethra 12 or extends from the urethra 12 to the outside of the patient's body) can be provided. In one embodiment, the combined length of the proximal portion 128 and the central portion 126 of the tube 122 is approximately 54 ± 2 cm. In some embodiments, the tube 122 terminates within the bladder 10. In that case, the fluid is drained from the proximal end of the ureteral catheters 112, 114 and directed from the body through an additional indwelling bladder catheter. In another embodiment, the tube 122 is terminated within the urethra 12, for example, a bladder catheter is not required. In another embodiment, the tube extends from the urethra 12 to the outside of the patient's body and, for example, a bladder catheter is not required.
Illustrative ureteral retention part:

Any of the retention portions disclosed herein can be formed from the same material as the drainage lumen discussed above and can be integral with or connected to the drainage lumen. , Or the retaining portion can be formed from and connected to a material different from those discussed above with respect to the drain lumen. For example, the retaining moiety may be a material such as polyurethane, flexible polyvinyl chloride, polytetrafluoroethylene (PTFE), latex, silicone, silicon, polyglycolide or poly (glycolic acid) (PGA), polylactic acid (PGA). It can be formed from any of polymers such as PLA), poly (lactic acid-co-glycolic acid), polyhydroxyalkanoic acid, polycaprolactone, and / or poly (propylene fumarate).

In general, for example, as shown in FIGS. 2A-C, 8A, and 8B, the distal portion 118 of the ureteral catheter 112 places the distal end 120 of the catheter 112 close to the renal pelvis 20, 21 of the kidneys 2, 4. The retention portion 130 is provided for maintaining or in the desired fluid collection position within it. In some embodiments, the retention portion 130 is configured to be flexible and flexible to allow the retention portion 130 to be located within the ureter and / or the renal pelvis. The retention portion 130 is preferably flexible enough to absorb the forces applied on the catheter 112 and to prevent such forces from being transmitted to the ureter. For example, if the retention portion 130 is pulled towards the patient's bladder in the proximal direction P (shown in FIG. 9A), the retention portion 130 begins to unwind or straighten so that it can be pulled through the ureter. Can be flexible enough for. Similarly, when the retention portion 130 can be reinserted into the renal pelvis or other suitable area within the urinary tract, it can be urged to return to its unfolded configuration.

In some embodiments, the retention portion 130 is integral with the tube 122. In that case, the retention portion 130 can be formed by applying a bend or inflection to the catheter body 122 that is sized and shaped to retain the catheter in the desired fluid collection location. Suitable bends or coils can include pigtail coils, corkscrew coils, and / or spiral coils as shown in FIGS. 1, 2A, 7A, and 8A-10G. For example, the retention portion 130 brings the catheter 112 in the ureters 6, 8 in close proximity to or into the renal pelvis 20, 21, as shown, for example, in FIGS. 2A, 7A, and 8A-10G. It may include one or more radial and longitudinally extending spiral coils configured to passively retain. In another embodiment, the retention portion 130 is formed from a radially flared or tapered portion of the catheter body 122. For example, the retention portion 130 can further include a fluid collection portion as shown in FIGS. 17-41C, such as a tapered or funnel-shaped inner surface 186. In another embodiment, the retention portion 130 can comprise a separate element that is connected to and extends from the catheter body or tube 122.

In some embodiments, the retention portion 130 further has a drain hole, a perforation, or a port 132, 1232 (eg, FIGS. 9A-9E, 10A, 10E, 11-14, 27, 32A, 32B, 33, 34, and One or more perforation sections such as (shown in 39-41A-C) can be provided. The drain port 132 can be located, for example, at the open distal ends 120, 121 of the tube 122, as shown in FIG. 10D. In other embodiments, the perforations and / or drain ports 132, 1232 are as shown in FIGS. 9A-9E, 10A, 10E, 11-14, 27, 32A, 32B, 33, 34, and 41A-C. , Along the side wall 109 of the distal portion 118 of the catheter tube 122, or within the material of the retaining portion, such as the sponge material of FIGS. 39 and 40. The drain ports or holes 132, 1232 can be used to assist fluid collection, whereby fluid can flow into the drain lumen for removal from the patient's body. In another embodiment, the retention portion 130 is dedicated to the reservoir structure and fluid collection, and / or the application of negative pressure is provided by the structure elsewhere on the catheter tube 122.

In some embodiments as shown in FIGS. 9B-E, 10D-G, 18B, 18C-E, 20, 22A-35, 37B, 38A, 39B, 40A-41C, a drain hole, port, or perforation 132. , At least part, most, or all of 1232, tissue 1004, 1003 from the bladder or kidney does not come into direct contact with the protected drain, port, or perforation 133, or partially or completely occludes it. It is positioned within the ureteral catheter 112, 114 or bladder catheter 116 within a protected surface area or medial surface area 1000 so as not to. For example, when negative pressure is induced in the ureter and / or renal pelvis, as shown in FIGS. 2A-2C, 7A, 7B, 10F, 17, 18D, 24B, 29C, 39B, 40B, and 41B. A portion of the mucosal tissue 1003 of the ureter and / or kidney can be pulled against the outer margin 72, 1002 or protective surface area 1001 or outer region of the retention portion 130 and the outer margin 72, 1002 or protective surface area of the retention portion 130. Some drain holes, ports, or perforations 134, located on 1001, may be partially or completely blocked. Similarly, as shown in FIGS. 2A-2C, 7A, 7B, 10G, 17, 18E, 24C, 39C, 40C, and 41C, when negative pressure is induced in the bladder, the transitional epithelial tissue inner layer, endemic. A portion of bladder tissue 1004, such as layered connective tissue, lamina propria, and / or fatty connective tissue, can be pulled with respect to the outer peripheral edge 72, 1002 or protective surface area 1001 or outer region of retention portion 130, the retention portion. Some drain holes, ports, or perforations 134 located on the outer perimeter 1002 or protective surface area 1001 or outer region of 130 may be partially or completely blocked.

At least a portion of the protected discharge port 133 located on the protected surface area or inner surface area 1000 of the retention portion 130 is such tissue 1003, 1004 on the outer periphery 72, 1002 or protection surface area 1001 of the retention portion 130 or When contacting the outer area, it will not be partially or completely occluded. In addition, the risk of injury to tissues 1003, 1004 from biting or contact with drain port 133 can be reduced or ameliorated. The configuration of the outer peripheral edges 72, 1002 or the protective surface area 1001 or outer region of the retention portion 130 depends on the overall configuration of the retention portion 130. In general, the outer margin 72, 1002 or protective surface area 1001 or outer region of the retention portion 130 contacts and supports the bladder 1004 or kidney tissue 1003, thereby protecting the cloaca, port, or perforation 133. Prevent obstruction or obstruction.

For example, as shown in FIGS. 10E-G, an exemplary retention portion 1230 comprising a plurality of spiral coils 1280, 1282, 1284 is shown. The outer peripheral edge 1002 or protected surface area 1001 or outer region of the spiral coils 1280, 1282, 1284 contact and support the bladder tissue 1004 or kidney tissue 1003, and the protected surface area or inner side of the spiral coils 1280, 1282, 1284. Prevents blockage or obstruction of protected drain holes, ports, or perforations 1233 located within a surface area of 1000. The outer peripheral edges 1002 or protected surface area 1001 or outer region of the spiral coils 1280, 1282, 1284 provide protection for protected drain holes, ports, or perforations 1233. In FIG. 10F, kidney tissue 1003 surrounds and contacts the outer peripheral edges 1002 or protected surface area 1001 or outer region of spiral coils 1280, 1282, 1284, which are shown in spiral coils 1280, 1282. , 1284's protected surface area or inner surface area 1000's contact with the kidney tissue 1003, thereby preventing partial or complete obstruction of the protected drain holes, ports, or perforations 1233 by the kidney tissue 1003. In FIG. 10G, the bladder tissue 1004 surrounds and contacts the outer peripheral edges 1002 or the protective surface area 1001 or the outer region of the spiral coils 1280, 1282, 1284, which are shown in contact with the spiral coils 1280, 1282. , 1284's protected surface area or inner surface area 1000's contact with the bladder tissue 1004, thereby preventing partial or complete obstruction of the protected drain holes, ports, or perforations 1233 by the bladder tissue 1004.

Similarly, FIGS. 1, 2A, 7A, 17, 18A, 18B, 18C, 19, 20, 21, 22A, 22B, 23A, 23B, 24, 25, 26, 27, 28A, 28B, 29A, 29B, 30, Other examples of the configuration of the bladder and / or ureteral retainer set forth in 31, 32A, 32B, 33, 34, 35A, 35B, 36, 37A, 37B, 38A, 38B, 39, 40, and 41. Obstruction or obstruction of a protected drain, port, or perforation 133, 1233 that contacts and supports the bladder tissue 1004 or kidney tissue 1003 and is located within the protected surface area or inner surface area 1000 of the retention portion. Provides an outer peripheral edge 1002 or a protective surface area 1001 or an outer region that can thwart. Each of these examples will be further discussed below.

See here in FIGS. 8A, 8B, and 9A-9E for a ureteral or bladder catheter with multiple helical coils such as one or more complete coils 184 and one or more semi- or partial coils 183. An exemplary retention portion 130 is illustrated. The retention portion 130, along with the plurality of spiral coils, is movable between the contraction position and the deployment position. For example, a substantially straight guide wire can be inserted through the retention portion 130 to maintain the retention portion 130 in a substantially linear contraction position. When the guide wire is removed, the retaining portion 130 can transition to its coiled configuration. In some embodiments, the coils 183, 184 extend radially and longitudinally from the distal portion 118 of the tube 122. With specific reference to FIGS. 8A and 8B, in an exemplary embodiment, the retention portion 130 comprises two complete coils 184 and one half coil 183. For example, as shown in FIGS. 8A and 8B, the outer diameter of the complete coil 184 indicated by line D1 can be about 18 ± 2 mm and the diameter D2 of the half coil 183 is about 14 mm ± 2 mm. The coiled retaining portion 130 can have a height H of about 16 ± 2 mm.

The retention portion 130 further comprises one or more drain holes 132, 1232 (eg, shown in FIGS. 9A-9E, 10A, and 10E) configured to draw fluid into the interior of the catheter tube 122. be able to. In some embodiments, the retention portion 130 has two, three, four, five, six, seven, eight, or more outlet holes 132, 1232 plus additional holes 110. It can be provided at the distal tip or end 120 of the retention portion. In some embodiments, the respective diameters of the drain holes 132, 1232 (eg, shown in FIGS. 9A-9E, 10A, and 10E) can range from about 0.7 mm to 0.9 mm, preferably. , Approximately 0.83 ± 0.01 mm. In some embodiments, the diameter of the additional hole 110 (eg, shown in FIGS. 9A-9E, 10A, and 10E) at the distal tip or end of the retention portion 130 is from about 0.165 mm to about 2.39 mm. , Or can range from about 0.7 to about 0.97 mm. The distance between adjacent discharge holes 132, specifically the linear distance between the closest outer edges of the discharge holes 132, 1232 when the coil is straightened, is about 15 mm ± 2.5 mm, or about 22.5 ±. It can be 2.5 mm or more.

As shown in FIGS. 9A-9E, in another exemplary embodiment, the distal portion 118 of the drainage lumen 124 proximal to the retention portion 130 defines a straight or curved central axis L. In some embodiments, at least half or the first coil 183 of the retention portion 130 and the complete or second coil 184 extend around axis A of the retention portion 130. The first coil 183 starts or rises from the point where the tube 122 bends at an angle α ranging from about 15 degrees to about 75 degrees, preferably about 45 degrees, from the central axis L, as indicated by the angle α. Start. As shown in FIGS. 9A and 9B, the axis A can be co-extended with the longitudinal central axis L prior to insertion into the body. In another embodiment, as shown in FIGS. 9C-9E, prior to insertion into the body, axis A extends from the central vertical axis L and is, for example, curved or angled at an angle β relative to it. Be done.

In some embodiments, the plurality of coils 184 can have the same or different inner and / or outer diameter D and height H2 between adjacent coils 184. In that case, each outer diameter D1 of the coil 184 may range from about 10 mm to about 30 mm. The height H2 between each of the adjacent coils 184 may range from about 3 mm to about 10 mm.

In another embodiment, the retention portion 130 is configured to be inserted into the tapered portion of the renal pelvis. For example, the outer diameter D1 of the coil 184 can be increased towards the distal end 120 of the tube 122 to result in a helical structure with a tapered or partially tapered configuration. For example, the distal or maximum outer diameter D1 of the tapered spiral portion ranges from about 10 mm to about 30 mm, corresponding to the dimensions of the renal pelvis, and the outer diameter D1 of each adjacent coil is the proximal end 128 of the retention portion 130. Can decrease closer. The overall height H of the retention portion 130 can range from about 10 mm to about 30 mm.

In some embodiments, the outer diameter D1 of each coil 184 and / or the height H2 between each of the coils 184 can vary in a regular or irregular manner. For example, the outer diameter D1 of the coils or the height H2 between adjacent coils can be increased or decreased by a regular amount (eg, about 10% to about 25% between adjacent coils 184). For example, with respect to the retention portion 130 having three coils (eg, as shown in FIGS. 9A and 9B), the outer diameter D2 of the nearest coil or the first coil 183 can be about 6 mm to 18 mm. The outer diameter D3 of the central coil or the second coil 185 can be from about 8 mm to about 24 mm, and the outer diameter D13 of the most distal or third coil 187 can be from about 10 mm to about 30 mm. ..

The retention portion 130 further comprises a drainage perforation, a hole, or a port 132 that is located on or through the sidewall 109 of the catheter tube 122 on or adjacent to the retention portion 130 so that urine waste is in the catheter tube 122. It can be allowed to flow from the outside of the catheter tube 122 to the medial drainage lumen 124 of the catheter tube 122. The location and size of the discharge port 132 can vary depending on the desired fluxion and configuration of the retention portion 130. Each diameter D11 of the discharge port 132 can independently range from about 0.005 mm to about 1.0 mm. The spacing D12 between each of the closest edges of the discharge port 132 can independently range from about 1.5 mm to about 5 mm. The discharge ports 132 can be spaced in any arrangement, eg, random, linear, or offset arrangement. In some embodiments, the discharge port 132 can be non-circular and can have a surface area of about 0.00002 to 0.79 mm ² .

In some embodiments, as shown in FIG. 9A, the drain port 132 is located around the outer peripheral edge 72, 1002 or the entire protective surface area 1001 of the sidewall 109 of the catheter tube 122 and into the drain lumen 124. Increase the amount of fluid that can be drawn (shown in FIGS. 2, 9A, and 9B). In another embodiment, as shown in FIGS. 9B-9E and 10-10E, the drain holes, ports, or perforations 132 are essentially a protected surface area or inner surface area of 1000 or radial inward of the coil 184. Located only on or only on the facing side 1286, the discharge ports 132, 1232 can be prevented from blocking or interfering, and the outward facing side 1288 of the coil is essentially discharge ports 132, 1232. Or may not have discharge ports 132, 1232. The outer peripheral edges 72, 189, 1002 or protective surface area 1001 or outer region 192 of the spiral coils 183, 184, 1280, 1282, 1284 contact and support the bladder tissue 1004 or kidney tissue 1003 and support the spiral coils 183, 184. , 1280, 1282, 1284's protected surface area or inside surface area 1000, can prevent blockage or obstruction of protected drain holes, ports, or perforations 133, 1233. For example, when negative pressure is induced in the ureter and / or renal pelvis, the mucosal tissue of the ureter and / or kidney can be pulled with respect to the retention portion 130 and the lateral margins 72, 189, 1002 of the retention portion 130. Some of the above discharge ports 134 can be blocked. Discharge ports 133, 1233 located on the radial inward side 1286 or protected surface area or inner surface area 1000 of the reservoir structure, such tissue 1003, 1004 is the outer peripheral edge 72, 189, 1002 or protection of the retention portion 130. When in contact with surface area 1001 or the outer region, it will not be significantly blocked. In addition, the risk of tissue injury from biting or contact with drain ports 132, 133, 1233, or protected drain holes, ports, or perforations 133, 1233 can be reduced or ameliorated.

Referring to FIGS. 9C and 9D, another embodiment of the ureteral catheter 112 having a retention portion 130 with a plurality of coils 184 is illustrated. As shown in FIG. 9C, the retention portion 130 includes three coils 184 extending about the axis A. The axis A is a curved arc extending from the central vertical axis L of a portion of the drainage lumen 181 proximal to the retention portion 130. The curvature imparted to the retention portion 130 can be selected to correspond to the curvature of the renal pelvis, which comprises a conical vessel-shaped cavity.

As shown in FIG. 9D, in another exemplary embodiment, the retention portion 130 may include two coils 184 extending about an angled axis A. The angled axis A extends at an angle from the central vertical axis L and is angled with respect to an axis substantially perpendicular to the central axis L of a portion of the drainage lumen, as indicated by the angle β. The angle β can range from about 15 to about 75 degrees (eg, about 105 to about 165 degrees with respect to the central vertical axis L of the drainage lumen portion of the catheter 112).

FIG. 9E shows another embodiment of the ureteral catheter 112. The retention portion comprises three spiral coils 184 extending about the axis A. The axis A is angled with respect to the horizontal, as indicated by the angle β. As in the previous embodiment, the angle β can range from about 15 to about 75 degrees (eg, about 105 to about 165 degrees with respect to the central longitudinal axis L of the drainage lumen portion of the catheter 112).

In some embodiments shown in FIGS. 10-10E, the retention portion 1230 is integral with the tube 1222. In another embodiment, the retention portion 1230 can be provided with a separate tubular member connected to and extending from the tube or drain lumen 1224.

In some embodiments, the retention portion comprises a plurality of radial extending coils 184. The coil 184 is configured in the shape of a funnel, thereby forming a funnel-shaped support. Some examples of coiled funnel supports are shown in FIGS. 2A-C, 7A, 7B, 8A, and 8A-10E.

In some embodiments, at least one side wall 119 of the funnel-shaped support comprises at least a first coil 183 having a first diameter and a second coil 184 having a second diameter. The first diameter is less than the second diameter and the maximum distance between part of the side wall of the first coil and part of the adjacent side wall of the second coil is from about 0 mm to about 10 mm. It reaches. In some embodiments, the first diameter of the first coil 183 ranges from about 1 mm to about 10 mm and the second diameter of the second coil 184 ranges from about 5 mm to about 25 mm. In some embodiments, the diameter of the coil increases towards the distal end of the drainage lumen, resulting in a helical structure with a tapered or partially tapered configuration. In some embodiments, the second coil 184 is closer to the end of the distal portion 118 of the drain lumen 124 than the first coil 183. In some embodiments, the second coil 184 is closer to the end of the proximal portion 128 of the drain lumen 124 than the first coil 183.

In some embodiments, at least one side wall 119 of the funnel-shaped support comprises an inwardly facing side 1286 and an outwardly facing side 1288, as discussed below, inwardly. The facing side 1286 comprises at least one opening 133, 1233 to allow fluid flow into the drainage lumen, and the outward facing side 1288 has essentially no opening, or do not have. In some embodiments, at least one opening 133, 1233 has an area ranging from about 0.002 mm ² to about 100 mm ² .

In some embodiments, the first coil 1280 comprises a side wall 119 comprising a radial inward facing side 1286 and a radial outward facing side 1288, the radius of the first coil 1280. The inward facing side 1286 comprises at least one opening 1233 to allow fluid flow into the drainage lumen.

In some embodiments, the first coil 1280 comprises a side wall 119 comprising a radial inward facing side 1286 and a radial outward facing side 1288, the radius of the first coil 1280. The inward facing side 1286 comprises at least two openings 1233 to allow fluid flow into the drainage lumen 1224.

In some embodiments, the first coil 1280 comprises a side wall 119 comprising a radial inward facing side 1286 and a radial outward facing side 1288, the radius of the first coil 1280. The outward facing side 1288 is essentially free or absent of one or more openings 1232.

In some embodiments, the first coil 1280 comprises a side wall 119 with a side 1286 facing inward in the radial direction and a side 1288 facing outward in the radial direction, and the radius of the first coil 1280. The inwardly facing side 1286 comprises at least one opening 1233 to allow fluid flow into the drainage lumen 1224, and the radially outwardly facing side 1288 has one or more openings. The opening 1232 is essentially absent or absent.

Now referring to FIGS. 10-10E, in some embodiments, the distal portion 1218 comprises an open distal end 1220 for drawing fluid into the drainage lumen 1224. The distal portion 1218 of the ureteral catheter 1212 further comprises a retention portion 1230 for maintaining the distal portion 1218 of the drainage lumen or duct 1222 within the ureter and / or the kidney. In some embodiments, the retention portion 1230 comprises a plurality of radial extending coils 1280, 1282, 1284. The retention portion 1230 is flexible and flexible and can allow positioning of the retention portion 1230 within the ureter, renal pelvis, and / or kidney. For example, the retention portion 1230 is preferably flexible enough to absorb the forces applied on the catheter 1212 and prevent such forces from being transmitted to the ureter. Further, if the retention portion 1230 is pulled in the proximal direction P (shown in FIGS. 9A-9E) towards the patient's bladder 10, the retention portion 1230 can be pulled through the ureters 6 and 8. It can be flexible enough to begin unwinding or straightening. In some embodiments, the retention portion 1230 is integral with the tube 1222. In another embodiment, the retention portion 1230 can be provided with a separate tubular member connected to and extending from the tube or drain lumen 1224. In some embodiments, the catheter 1212 comprises a radiodensity band 1234 (shown in FIG. 29) located on the tube 1222 at the proximal end of the retention portion 1230. The radiodensity band 1234 is visible by fluoroscopic imaging during deployment of catheter 1212. In particular, the user can monitor the advance of band 1234 through the urinary tract by fluoroscopy and determine when the retention portion 1230 is in the renal pelvis and ready for deployment.

In some embodiments, the retention portion 1230 comprises a perforation, drain port, or opening 1232 within the side wall of the tube 1222. As described herein, the location and size of the openings 1232 can vary depending on the desired volumetric flow rate for each opening and the size constraints of the retention portion 1230. In some embodiments, each diameter D11 of the opening 1232 can independently range from about 0.05 mm to about 2.5 mm and have an area of about 0.002 mm ² to about 5 mm ² . The opening 1232 can be positioned so as to extend along the side wall 119 of the tube 1222 in any desired direction, such as longitudinal and / or axial. In some embodiments, the spacing between each of the closest adjacent edges of the opening 1232 can range from about 1.5 mm to about 15 mm. The fluid passes through the drainage lumen 1234 through one or more of the perforations, drainage ports, or openings 1232. Desirably, the openings 1232 are positioned so that when negative pressure is applied to the drainage lumen 1224, they are not obstructed by the tissues of the ureters 6, 8 or kidney 1003. For example, as described herein, the opening 1233 is located on an internal portion of the coil or other structure of the retaining portion 1230 or on a protected surface area 1000 to avoid blockage of the openings 1232, 1233. can do. In some embodiments, the central portion 1226 and proximal portion 1228 of the tube 1222 have essentially no or no perforations, ports, openings, or openings of openings along those portions of the tube 1222. Blockage can be avoided. In some embodiments, portions 1226, 1228, which are essentially free of perforations or openings, include an opening 1232 that is substantially less than other parts, such as the distal portion 1218 of the tube 1222. For example, the total area of the opening 1232 of the distal portion 1218 may be greater than or substantially greater than the total area of the opening of the central portion 1226 and / or the proximal portion 1228 of the tube 1222.

In some embodiments, the openings 1232 are sized and spaced to improve fluid flow through the retention portion 1230. In particular, we have discovered that when negative pressure is applied to the drainage lumen 1224 of the catheter 1212, most of the fluid is drawn into the drainage lumen 1224 through a recent perforation or opening 1232. .. Larger size or more openings 1232 to improve fluid dynamics so that fluid is also received through the more distal openings and / or through the open distal end 1220 of the tube 1222. Can be provided towards the distal end 1220 of the retention portion 1230. For example, the total area of the opening 1232 on the length of the tube 1222 near the proximal end 1228 of the retention portion 1230 is of a similar size length of the tube 1222 located near the open distal end 1220 of the tube 1222. It may be less than the total area of the opening 1232. In particular, less than 90%, preferably less than 70%, more preferably less than 55% of the fluid flow is a single opening 1232 located in the drain cavity 1224 near the proximal end 1228 of the retention portion 1230. Alternatively, it may be desirable to produce a flow distribution through the drainage lumen 1224, which is drawn through a small number of openings 1232.

In many embodiments, the opening 1232 is generally circular, but triangles, ellipses, squares, rhombuses, and any other opening shape may also be used. Further, as will be appreciated by those skilled in the art, the shape of the opening 1232 may change as the tube 1222 transitions between the non-coiled or extended position and the coiled or deployed position. The shape of the opening 1232 may vary (eg, the orifice may be circular in some positions and slightly extended in other positions), but the area of the opening 1232 may be expanded or expanded. Note that it is substantially similar in the extended or non-coiled position as compared to the coiled position.

In some embodiments, the drainage lumen 1224 defined by the tube 1222 is one of the tubes 1222 configured to be located within the distal portion 1218 (eg, ureters 6, 8 and renal pelvis 20, 21). A portion (eg, shown in FIGS. 7A and 10) and a central portion 1226 (eg, configured to extend from the distal portion through the ureteral opening 16 into the patient's bladder 10 and urethra 12). It comprises a portion of the tube 1222 (shown in FIGS. 7A and 10) and a proximal portion 1228 (eg, a portion of the tube 1222 extending from the urethra 12 to the external fluid collection vessel and / or pump 2000). .. In one embodiment, the combined length of the proximal portion 1228 and the central portion 1226 of the tube 1222 is approximately 54 ± 2 cm. In some embodiments, the central portion 1226 and proximal portion 1228 of the tube 1222 include a distance marking 1236 (shown in FIG. 10) on the side wall of the tube 1222, which is the tube during deployment of the catheter 1212. 1222 can be used to determine the distance inserted into the patient's urinary tract.

As shown in FIGS. 7A and 10-14, the exemplary ureteral catheter 1212 comprises at least one extension body or tube 1222, within which one or more drainage channels or lumens, such as a drainage lumen 1224, are provided. To define or prepare for. Tube 1222 sizes can range from about 1 Fr to about 9 Fr (French catheter scale). In some embodiments, the tube 1222 can have an outer diameter ranging from about 0.33 to about 3.0 mm and an inner diameter ranging from about 0.165 to about 2.39 mm. In one embodiment, the tube 1222 is 6 Fr and has an outer or outer diameter of 2.0 ± 0.1 mm. The total length of the tube 1222 can range from about 30 cm to about 120 cm, depending on the patient's age (eg, child or adult) and gender.

The tube 1222 is flexible to facilitate advancement and / or positioning of the tube 1222 within the bladder 10 and ureters 6, 8 (shown in FIG. 7), such as any of the materials discussed above. And / or can be formed from a deformable material. For example, the tube 1222 is formed from one or more materials such as biocompatible polymers, polyvinyl chloride, polytetrafluoroethylene (PTFE) such as Teflon®, silicon coated latex, or silicon. Can be done. In one embodiment, the tube 1222 is made of thermoplastic polyurethane.
Spiral coil retention part

Referring here to FIGS. 10A-10E, the exemplary retention portion 1230 comprises spiral coils 1280, 1282, 1284. In some embodiments, the retention portion 1230 comprises a first or half coil 1280 and two complete coils such as a second coil 1282 and a third coil 1284. As shown in FIGS. 10A-10D, in some embodiments, the first coil 1280 comprises a half coil extending 0 to 180 degrees around the curve center axis A of the retention portion 1230. In some embodiments, as shown, the curve center axis A is a substantially straight line and is co-extended to the curve center axis of the tube 1222. In another embodiment, the curve center axis A of the retention portion 1230 is curved so that the retention portion 1230 can be subject to, for example, a conical container shape. The first coil 1280 can have a diameter D1 of about 1 mm to 20 mm, preferably about 8 mm to 10 mm. The second coil 1282 extends 180 degrees to 540 degrees along the retention portion 1230, having a diameter D2 of about 5 mm to 50 mm, preferably about 10 mm to 20 mm, more preferably about 14 mm ± 2 mm, complete. It can be a coil. The third coil 1284 can be a complete coil extending 540 to 900 degrees and having a diameter D3 of 5 mm and 60 mm, preferably about 10 mm to 30 mm, more preferably about 18 mm ± 2 mm. In another embodiment, the plurality of coils 1282, 1284 can have the same inner diameter and / or outer diameter. For example, the outer diameters of the complete coils 1282 and 1284 can be about 18 ± 2 mm, respectively.

In some embodiments, the total height H of the retention portion 1230 ranges from about 10 mm to about 30 mm, preferably about 18 ± 2 mm. The height H2 of the gap between the adjacent coils 1284, that is, between the side wall 1219 of the tube 1222 of the first coil 1280 and the adjacent side wall 1221 of the tube 122 of the second coil 1282, is preferably less than 3.0 mm. Is about 0.25 mm to 2.5 mm, more preferably about 0.5 mm to 2.0 mm.

The retention portion 1230 can further comprise a distal curved portion 1290. For example, the most distal portion 1290 of the retention portion 1230, including the open distal end 1220 of the tube 1222, can be bent inward with respect to the curvature of the third coil 1284. For example, the curve center axis X1 of the most distal portion 1290 (shown in FIG. 10D) can extend from the distal end 1220 of the tube 1222 towards the curve center axis A of the retention portion 1230.

The retention portion 1230 moves between a contraction position where the retention portion 1230 is straight for insertion into the patient's urinary tract and a deployment position where the retention portion 1230 comprises spiral coils 1280, 1282, 1284. It is possible to do. In general, the tube 1222 is inevitably urged towards the coiled configuration. For example, a non-coiled or substantially straight guide wire can be inserted through the retention portion 1230 to keep the retention portion 1230 in its linear contraction position, eg, as shown in FIGS. 11-14. When the guide wire is removed, the retaining portion 1230 inevitably transitions to its coiled position.

In some embodiments, the openings 1232, 1233 are essentially located on the radially inward facing side 1286 or protected surface area or inner surface area 1000 of the coils 1280, 1282, 1284, or only on that side. The openings 1232, 1233 are blocked or obstructed. The radial outward facing side 1288 of the coils 1280, 1282, 1284 may be essentially free of openings 1232. In a similar embodiment, the total area of the openings 1232, 1233 on the inwardly facing side 1286 of the retention portion 1230 is the total area of the openings 1232 on the radially outward facing side 1288 of the retention portion 1230. Can be substantially exceeded. Thus, when negative pressure is induced in the ureter and / or renal pelvis, the mucosal tissue of the ureter and / or kidney can be pulled against the retention portion 1230 and the outer margin 1002 or protection surface area 1001 of the retention portion 1230. Some of the above openings 1232 can be blocked. However, an opening 1232 located on the radial inward facing side 1286 or protected surface area or inner surface area 1000 of the retaining portion 1230 allows such tissue to be on the outer peripheral edge 1002 or protected surface area 1001 of the retaining portion 1230. When in contact, it is not significantly blocked. Therefore, the risk of tissue damage from biting or contact with the discharge opening 1232 can be reduced or eliminated.
Hole or opening distribution Example

In some embodiments, the first coil 1280 can have no or essentially no opening 1232. For example, the total area of the openings 1232 on the first coil 1280 can be less than or substantially less than the total area of the openings 1232 of the complete coils 1282, 1284. Examples of various arrangements of openings or openings 1232 that can be used for coiled retainers (such as the coiled retainer 1230 shown in FIGS. 10A-10E) are illustrated in FIGS. 11-14. As shown in FIGS. 11-14, the retention portion 1330 is depicted in its non-coiled or linear position as it occurs when the guide wire is inserted through the drain lumen.

An exemplary retention portion 1330 is illustrated in FIG. In order to more clearly explain the positioning of the opening of the retention portion 1330, the retention portion 1330 is referred to herein as the most recent or first division 1310, second division 1312, third division 1314, fourth. 1316, a fifth section 1318, and a plurality of sections or perforation sections such as the most distal or sixth section 1320. Those skilled in the art will appreciate that less or additional categories may be included, if desired. As used herein, "classification" refers to the discrete length of tube 1322 within the retention portion 1330. In some embodiments, the compartments are equal in length. In other embodiments, some compartments can have the same length and other compartments can have different lengths. In other embodiments, each section has a different length. For example, compartments 1310, 1312, 1314, 1316, 1318, and 1320 can each have a length L1-L6 ranging from about 5 mm to about 35 mm, preferably about 5 mm to 15 mm, respectively.

In some embodiments, each segment 1310, 1312, 1314, 1316, 1318, and 1320 comprises one or more openings 1332. In some embodiments, each section comprises a single opening 1332. In another embodiment, the first section 1310 comprises a single opening 1332 and the other section comprises a plurality of openings 1332. In another embodiment, the different compartments comprise one or more openings 1332, each of which has a different shape or a different total area.

In some embodiments, such as the retention portion 1230 shown in FIGS. 10A-10E, the first or half coil 1280 extending from 0 to about 180 degrees of the retention portion 1230 has no openings or is essentially. Can not be. The second coil 1282 can include a first section 1310 that extends approximately 180-360 degrees. The second coil 1282 can also include second and third compartments 1312, 1314, located approximately 360 to 540 degrees of the retention portion 1230. The third coil 1284 can include fourth and fifth compartments 1316, 1318 located at about 540 to 900 degrees of the retention portion 1230.

In some embodiments, the opening 1332 may be sized so that the total area of the openings in the first section 1310 is less than the total area of the openings in the adjacent second section 1312. can. Similarly, if the retention portion 1330 further comprises a third section 1314, the opening of the third section 1314 has a total area that exceeds the total area of the openings of the first section 1310 or the second section 1312. Can have. The openings in the fourth section 1316, the fifth section 1318, and the sixth section 1320 also have a gradual increase in total area and / or number of openings to improve fluid flow through the tube 1222. You may.

As shown in FIG. 11, the retaining portion 1230 of the tube comprises five compartments 1310, 1312, 1314, 1316, 1318, each comprising a single opening 1332, 1334, 1336, 1338, 1340. The retention portion 1330 also includes a sixth section 1320, which includes the open distal end 1220 of the tube 1222. In this embodiment, the opening 1232 of the first section 1310 has a minimum total area. For example, the total area of the opening 1332 in the first category is about 0.002 mm ² to about 2.5 mm ² , or about 0.01 mm ² to 1.0 mm ² , or about 0.1 mm ² to 0.5 mm ² . Can reach. In one embodiment, the opening 1332 is about 55 mm from the distal end 1220 of the catheter and has a diameter of 0.48 mm and an area of 0.18 mm ² . In this embodiment, the total area of the opening 1334 of the second section 1312 exceeds the total area of the opening 1232 of the first section 1310 and ranges from about 0.01 mm ² to about 1.0 mm ² . Can be done. The third opening 1336, the fourth opening 1338, and the fifth opening 1350 can also range in size from about 0.01 mm ² to about 1.0 mm ² . In one embodiment, the second opening 1334 is about 45 mm from the distal end of the catheter 1220 and has a diameter of about 0.58 mm and an area of about 0.27 mm ² . The third opening 1336 can be about 35 mm from the distal end of the catheter 1220 and have a diameter of about 0.66 mm. The fourth opening 1338 can be about 25 mm from the distal end 1220 and have a diameter of about 0.76 mm. The fifth opening 1340 is about 15 mm from the distal end 1220 of the catheter and can have a diameter of about 0.889 mm. In some embodiments, the open distal end 1220 of tube 1222 has a maximum opening with an area ranging from about 0.5 mm ² to about 5.0 mm ² or larger. In one embodiment, the open distal end 1220 has a diameter of about 0.97 mm and an area of about 0.74 mm ² .

As described herein, openings 1332, 1334, 1336, 1338, 1340 are subjected to negative pressure applied, for example, from the proximal portion 1228 of the drainage lumen 1224 to the drainage lumen 1224 of the catheter 1212. Then, the volumetric flow rate of the fluid passing through the first opening 1332 can be positioned and sized so that it closely corresponds to the volumetric flow rate of the opening in the more distal section. As described above, if each opening has the same area, when negative pressure is applied to the drainage lumen 1224, the volumetric flow rate of the fluid passing through the nearest position of the first opening 1332 will be. It will substantially exceed the volumetric flow rate of the fluid passing through the opening 1334 closer to the distal end 1220 of the retention portion 1330. Although not intended to be constrained by any theory, when negative pressure is applied, the pressure difference between the inside of the drainage lumen 1224 and the outside of the drainage lumen 1224 becomes the most recent opening. It is believed to be larger in the region and diminished at each opening moving towards the distal end of the tube. For example, the size and location of openings 1332, 1334, 1336, 1338, 1340 is such that the volumetric flow rate for the fluid flowing into the opening 1334 of the second section 1312 is that of the opening 1332 of the first section 1310. It can be selected to be at least about 30% of the volumetric flow rate of the fluid flowing into it. In another embodiment, the volumetric flow rate for the fluid flowing in the most recent or first segment 1310 is less than about 60% of the total volumetric flow rate for the fluid flowing through the proximal portion of the drainage cavity 1224. .. In another embodiment, the volumetric flow rates for the fluid flowing into the openings 1332, 1334 of the two most recent sections (eg, first section 1310 and second section 1312) are negative pressures, eg, about. When a negative pressure of −45 mmHg is applied to the proximal end of the drainage lumen, it can be less than about 90% of the volumetric flow rate of the fluid flowing through the proximal portion of the drainage lumen 1224.

As will be appreciated by those of skill in the art, volumetric flow rates and distributions for catheters or tubes with multiple openings or perforations can be directly measured or calculated in a variety of different ways. As used herein, "volume flow rate" is for an actual measurement of volume flow rates downstream and adjacent to each opening or for "calculated volume flow rates" as described below. Means the use of the method.

For example, an actual measurement of the volume of fluid dispersed over time can be used to determine the volume flow rate through each opening 1332, 1334, 1336, 1338, 1340. In one exemplary experimental sequence, a multi-chamber vessel is provided around the retention portion 1330, comprising individual chambers sized to receive compartments 1310, 1312, 1314, 1316, 1318, 1320 of the retention portion 1330. It is sealed and can be encapsulated. Each opening 1332, 1334, 1336, 1338, 1340 may be sealed within one of the chambers. The amount of fluid volume drawn from the individual chambers into the tube 3222 through each opening 1332, 1334, 1336, 1338, 1340 is measured and over time into each opening when negative pressure is applied. The amount of fluid volume drawn can be determined. The cumulative amount of fluid volume collected in the tube 3222 by the negative pressure pump system will be comparable to the sum of the fluids drawn into each opening 1332, 1334, 1336, 1338, 1340.

Alternatively, volumetric fluid flow rates through different openings 1332, 1334, 1336, 1338, 1340 are mathematically calculated using equations for modeling fluid flow through tubular bodies. Can be done. For example, the volumetric flow rate of the fluid passing through the openings 1332, 1334, 1336, 1338, 1340 into the drainage lumen 1224 is described in detail below in connection with mathematical examples and FIGS. 15A-15C. As such, it can be calculated based on the material transfer shell balance assessment. Steps for deriving the mass balance equation and calculating the flow distribution between openings 1332, 1334, 1336, 1338, 1340 or the volumetric flow rates associated therewith are also described in detail below in connection with FIGS. 15A-15C. Will be done.

Another exemplary retention portion 2230 with openings 2332, 2334, 2336, 2338, 2340 is illustrated in FIG. As shown in FIG. 12, the retention portion 2230 comprises a number of smaller perforations or openings 2332, 2334, 2336, 2338, 2340. The openings 2332, 2334, 2336, 2338, 2340 can each have substantially the same cross-sectional area, or one or more openings 2332, 2334, 2336, 2338, 2340 have different cross-sectional areas. Can be done. As shown in FIG. 12, the retention portion 2330 comprises six sections 2310, 2312, 2314, 2316, 2318, 2320 as described above, where each section has a plurality of openings 2332, 2334, 2336. , 2338, 2340. In the embodiment shown in FIG. 12, the number of openings 2332, 2334, 2336, 2338, 2340 per section is such that the total area of openings 1332 within each section is increased compared to the proximally adjacent sections. As such, it increases towards the distal end 2220 of the tube 2222.

As shown in FIG. 12, the openings 2332 of the first section 2310 are arranged along the first virtual line V1 substantially parallel to the curve center axis X1 of the retention portion 2230. The openings 2334, 2336, 2338, 2340 of the second division 2312, the third division 2314, the fourth division 2316, and the fifth division 2318 have the openings 2334, 2336, 2338 of these divisions, respectively. The 2340 is also positioned on the side wall of the tube 2222 in an increasing number of rows so as to align around the circumference of the tube 2222. For example, some of the openings 2334 of the second section 2312 are such that the second virtual line V2 extending around the circumference of the side wall of the tube 2222 contacts at least a portion of the plurality of openings 2334. Positioned. For example, the second section 2312 may include two or more rows of perforations or openings 2334, where each opening 2334 has the same or different cross-sectional areas. Further, in some embodiments, at least one of the columns of the second section 2312 is parallel to the curve center axis X1 of the tube 2222, but not co-extended with the first virtual line V1. It can be aligned along the virtual line V3 of 3. Similarly, a third section 2314 may comprise a five-row perforation or opening 2336 in which each opening 2336 has the same or different cross-sectional area, and a fourth section 2316 may have seven rows of perforations or openings. A portion 2338 may be provided, and the fifth section 2318 may be provided with nine rows of perforations or openings 2340. As in the previous embodiment, the sixth section 2320 comprises a single opening, i.e., the open distal end 2220 of the tube 2222. In the embodiment of FIG. 12, each of the openings has the same area, but the area of one or more openings can be different, if desired.

Another exemplary retention portion 3230 with openings 3332, 3334, 3336, 3338, 3340 is illustrated in FIG. The retention portion 3230 of FIG. 13 includes a plurality of similarly sized perforations or openings 3332, 3334, 3336, 3338, 3340. As in the previous embodiment, the retention portion 3230 can be divided into six compartments 3310, 3312, 3314, 3316, 3318, 3320, each comprising at least one opening. The nearest or first segment 3310 includes one opening 3332. The second section 3312 includes two openings 3334 aligned along a virtual line V2 extending around the circumference of the side wall of the tube 3222. The third section 3314 comprises a group of three openings 3336 located at the vertices of the virtual triangle. The fourth section 3316 comprises a group of four openings 3338 located at the corners of a virtual square. The fifth section 3318 comprises 10 openings 3340 positioned to form a rhombus on the side wall of the tube 3222. As in the previous embodiment, the sixth section 3320 comprises a single opening, i.e., the open distal end 3220 of the tube 3222. The area of each opening can range from about 0.001 mm ² to about 2.5 mm ² . In the embodiment of FIG. 13, each of the openings has the same area, but the area of one or more openings can be different, if desired.

Another exemplary retention portion 4230 with openings 4332, 4334, 4336, 4338, 4340 is illustrated in FIG. The openings 4332, 4334, 4336, 4338, 4340 of the retention portion 4330 have different shapes and sizes. For example, the first section 4310 includes a single circular opening 4332. The second section 4312 has a circular opening 4334 with a cross-sectional area larger than the opening 4332 of the first section 4310. The third section 4314 comprises three triangular openings 4336. The fourth section 4316 comprises a large circular opening 4338. The fifth section 4318 comprises a diamond-shaped opening 4340. As in the previous embodiment, the sixth section 4320 comprises an open distal end 4220 of the tube 4222. FIG. 14 illustrates an embodiment of an array of differently shaped openings within each section. It is understood that the shape of each opening within each section can be independently selected, for example, the first section 4310 can have one or more diamond-shaped openings or other shapes. sea bream. The area of each opening can be the same or different and can range from about 0.001 mm ² to about 2.5 mm ² .

Calculation of Volume Flow Rate and Percentage of Flow Distribution Since the various arrangements of openings for the retention portion of the ureteral catheter 1212 have been described, the calculated percentage of flow distribution and the calculated volume flow rate through the catheter have been described. The method for determining will be described in detail here. A schematic diagram of an exemplary catheter with a side wall opening indicating the location of a portion of the tube or drainage lumen used in the calculations below is shown in FIG. The calculated percentage of the flow distribution refers to the percentage of total fluid flowing through the proximal portion of the drainage lumen that enters the drainage lumen through different openings or compartments of the retention portion. The calculated volumetric flow rate refers to the fluid flow rate per unit time through different parts of the drainage lumen or opening of the retention portion. For example, the volumetric flow rate for the proximal portion of the drainage lumen describes the flow rate for the total amount of fluid passing through the catheter. Volumetric flow rate for an opening refers to the volume of fluid that passes through the opening and into the drainage lumen per unit time. In Table 3-5 below, flow is described as a percentage of total fluid flow rate or total volume flow rate with respect to the proximal portion of the drain lumen. For example, an opening with a 100% flow distribution means that all fluid entering the drain lumen has passed through the opening. An opening with a 0% distribution would indicate that fluid within the drain lumen did not enter the drain lumen through the opening.

These volumetric flow rate calculations were used to determine and model the fluid flow through the retention portion 1230 of the ureteral catheter 1212 shown in FIGS. 7A and 10-10E. In addition, these calculations show that adjusting the area of the opening and the linear distribution of the openings along the holdings results in the distribution of fluid flow through different openings. For example, reducing the area of the recent opening reduces the proportion of fluid drawn through the recent opening into the catheter and increases the proportion of fluid drawn into the more distal opening of the retention portion. Let me.

For the following calculations, a tube length of 86 cm was used, with an inner diameter of 0.97 mm and an inner diameter of the end hole of 0.97 mm. The density of urine was 1.03 g / mL and had a coefficient of friction μ of 8.02 × 10-3 Pa · S (8.02 × 10-3 kg / s · m) at 37 ° C. The urine volume flow rate passing through the catheter was 2.7 ml / min (Q _Total ), as determined by experimental measurements.

The calculated volume flow rate passes through all the perforations or openings 1232 of the five compartments of the retention portion (referred to herein as volume flow _{Q2 -} Q6) and through the open distal end 1220. (Referred to herein as volumetric flow rate _Q1 ), the sum of the volumetric flow rates is, as shown in Equation 2, the proximal end of the tube 1222, 10 cm to 60 cm away from the last proximal opening. It is determined by the volumetric material balance equation, which is equal to the total volumetric flow rate (Q _Total ) exiting from.
Q _Total = Q ₁ + Q ₂ + Q ₃ + Q ₄ + Q ₅ + Q ₆ (Equation 2)

The modified loss factor (K') for each segment takes into account three types of loss factors within the catheter model, namely the resulting pressure drop at the pipe inlet (eg, the opening and open distal end of the pipe 1222). It is based on an inlet loss coefficient, a friction loss coefficient that takes into account the pressure loss that results from the friction between the fluid and the pipe wall, and a flow junction loss factor that takes into account the pressure loss that results from the interaction of the two flows together.

The inlet loss factor depends on the shape of the orifice or opening. For example, a tapered or nozzle-shaped orifice will increase the flow rate into the drain lumen 1224. Similarly, sharp edge orifices will have different flow properties than orifices with edges that are not clearly defined. For the purposes of the following calculations, it is assumed that the opening 1232 is a side orifice opening and the open distal end 1220 of the tube 1222 is a sharp edge opening. The cross-sectional area of each opening is considered constant through the pipe sidewall.

The friction loss factor approximates the pressure drop resulting from the friction between the fluid and the adjacent inner wall of the pipe 1222. Friction loss is defined according to the following equation.

The flow confluence loss factor is derived from the loss factor for combining flows at a branch angle of 90 degrees. Values for the loss factor were determined from Charts 13.10 and 13.11 of Miller DS, International Flow Systems, 1990 (incorporated herein by reference). The chart shows the ratio of the inlet orifice area (referred to as A1 in the chart) to the pipe cross-sectional area (referred to as A3 in the chart), the inlet orifice volume flow rate (Q1 in the chart) and the resulting combined pipe. The ratio of volume flow rate (Q3 in the chart) is used. For example, for an area ratio of 0.6 between the area of the opening and the area of the drain lumen, the following flow confluence loss factors (K ₁₃ and K ₂₃ ) will be used.

To calculate the total manifold loss factor (K), the model is separated into so-called "reference stations", the pressure of the two paths (eg, the flow through the opening and the flow through the drain lumen of the pipe) and It is necessary to gradually process and equilibrate the flow distribution to reach each station starting from the distal tip of the nearest "station". A graphical representation of the different stations used for this calculation is shown in FIG. For example, the most distal "station" A is the distal open end 1220 of tube 122. The second station A'is the most distal opening on the side wall of the tube 122 (eg, the opening of the fifth section 1318 in FIGS. 11-14). The next station B is for flow through the drain lumen 1224 just proximal to the A'opening.

To calculate the loss between station A (distal opening) and station B for fluid entering through the open distal end (path 1) of tube 1222, the correction loss factor (K') is equal to: Become.

Similarly, the second route to station B is through the opening 1334 of the fifth section 1318 (shown in FIGS. 11-14) of the retention portion 1330. The correction loss calculation for path 2 is calculated as follows.

The correction loss coefficients for both Path 1 and Path 2 must be equalized to ensure that the volumetric flow rates (Q ₁ and Q ₂ ) reflect the equilibrium distribution within the manifold at Station B. The volume flow rate is adjusted until an equal correction loss factor for both paths is achieved. The volume flow rate can be adjusted to represent a fraction of the total volume flow rate ( _Q'Total ), which is assumed to be 1 for the purposes of this stepwise solution. Corresponding to the equalization of the two correction loss coefficients, one can then proceed to the equalization of the two paths and reach station C (fourth segment 1316 in FIGS. 11-14).

The loss coefficients between station B (flow through the lumen in the fifth section 1318) and station C (flow through the lumen in the fourth section 1316) are equations 5.1 and 5.2. Calculated in a similar fashion, as indicated by. For example, for path 1 (station B to station C), the correction loss factor (K') for the opening of the fourth section 1316 is defined as follows.

For path 2 (stations B to C), the correction loss factor (K') based on the flow area of the opening of the fourth section 1316 is defined as follows.

As with the previous station, the correction loss coefficients for both Path 1 and Path 2 ensure that the volumetric flow rates (Q ₁ , Q ₂ , and Q ₃ ) reflect the equilibrium distribution within the manifold to station C. Must be equalized to. Depending on the equalization of the two correction loss coefficients, one can then proceed to the equalization of the two paths to reach station D, station E, and station F. The stepwise solution process proceeds through each station as demonstrated until the final station, in this case the correction loss factor for station F, is calculated. The total loss factor (K) for the manifold can then be calculated using the actual Q _Total (volume flow rate through the proximal portion of the drain lumen) determined through experimental measurements.

The fractional volumetric flow rates calculated through the stepwise run are then multiplied by the actual total volumetric flow rates (Q _Total ), each opening 1232 (shown in FIG. 10-10E) and the open distal end 1220. The flow rate through can be determined.

Examples are provided below with respect to the calculated volumetric flow rates and are shown in Table 3-5 and FIGS. 15A-15C.
(Example 1)

The first embodiment illustrates the distribution of fluid flow in a retainer tube with different sized openings, corresponding to the embodiment of the retainer 1330 shown in FIG. As shown in Table 3, the nearest opening (Q6) has a diameter of 0.48 mm and the most distal opening (Q5) on the side wall of the tube has a diameter of 0.88 mm. The open distal end (Q6) of the tube had a diameter of 0.97 mm. Each opening was circular.

The flow distribution and the calculated percentage of volumetric flow rate were determined as follows.

To calculate the flow distribution for each "station" or opening, the calculated K'value is multiplied by the actual total volume flow rate (Q _Total ) to determine the flow rate through each perforation and distal end hole. Were determined. Alternatively, the calculated results can be presented as a percentage of total flow rate or flow distribution, as shown in Table 3. As shown in Table 3 and FIG. 15C, the percentage of flow distribution through the nearest opening (Q6) was 56.1%. The flow rate through the two nearest openings (Q6 and Q5) was 84.6%.

As demonstrated in Example 1, increasing the diameter of the perforation extending from the proximal region to the distal region of the retention portion of the tube results in a more uniformly dispersed flow across the retention portion.
(Example 2)

（実施例３） In Example 2, each opening has the same diameter and area. As shown in Table 4 and FIG. 15A, in that case, the flow distribution through the nearest opening is 86.2% of the total flow rate through the tube. The flow distribution through the second opening is 11.9%. Therefore, in this example, it was calculated that 98.1% of the fluid passing through the drain lumen entered the lumen through the two most recent openings. Compared to Example 1, Example 2 increased the flow rate through the proximal end of the tube. Therefore, Example 1 provides a wider flow distribution in which a larger percentage of the fluid enters the drainage lumen through an opening other than the nearest opening. Thus, fluid can be collected more efficiently through multiple openings, reducing fluid stasis and improving the distribution of negative pressure through the renal pelvis and / or kidney.

(Example 3)

Example 2 also illustrates the flow distribution for openings having the same diameter. However, as shown in Table 5, the openings are closer together (10 mm vs. 22 mm). As shown in Table 5 and FIG. 15B, 80.9% of the fluid passing through the drainage lumen entered the drainage lumen through the most recent opening (Q6). 96.3% of the fluid in the drain lumen entered the drain lumen through the two most recent openings (Q5 and Q6).

Here, in general, with reference to FIGS. 17-41C, more specifically FIG. 17, two exemplary ureteral catheters 5000, 5001 and bladder catheter 116 located in the patient's urinary tract are shown. There is. The ureteral catheters 5000 and 5001 drain the fluid such as urine from at least one of the patient's kidneys 2, 4, the renal pelvis 20, 21, or the ureters 6, 8 adjacent to the renal pelvis 20, 21. It is provided with ureters 5002 and 5003. The drainage cavities 5002, 5003 are configured to be located within the ureters 6, 8 adjacent to the patient's kidneys 2, 4, renal pelvis 20, 21, and / or renal pelvis 20, 21, distal portion 5004, It comprises a 5005 and proximal portions 5006, 5007 through which the fluid 5008 is drained out of the patient's bladder 10 or body, as shown in FIGS. 2B and 2C.

In some embodiments, the distal portions 5004, 5005 are provided with open distal ends 5010, 5011 for drawing fluid into the drainage lumens 5002, 5003. The distal portions 5004, 5005 of the ureteral catheters 5000, 5001 further provide retention portions 5012, 5013 to maintain the drainage lumen or distal portions 5004, 5005 of the tubes 5002, 5003 in the ureter and / or kidney. Be prepared. The retention portions 5012, 5013 are flexible and / or flexible and can allow positioning of the retention portions 5012, 5013 within the ureter, renal pelvis, and / or kidney. For example, the retention portions 5012, 5013 are preferably flexible enough to absorb the forces applied on the catheters 5000, 5001 and prevent such forces from being transmitted to the ureter. Further, if the retention portions 5012, 5013 are pulled towards the patient's bladder 10 in the proximal direction P (shown in FIG. 17), the retention portions 5012, 5013 may be withdrawn through the ureters 6, 8. In addition, it can be flexible enough to begin unwinding, straightening, or crushing.

In some embodiments, the retention portion comprises a funnel-shaped support. Non-limiting examples of different shapes of funnel-shaped supports are shown in FIGS. 7A, 7B, 17, and 18A-41C, discussed in detail below. Generally, the funnel-shaped support comprises at least one side wall. At least one side wall of the funnel-shaped support comprises a first diameter and a second diameter, the first diameter being less than the second diameter. The second diameter of the funnel-shaped support is closer to the end of the distal portion of the drainage lumen than the first diameter.

The drainage lumen or the proximal portion of the drainage tube has essentially no or no opening. Although not intended to be constrained by any theory, when negative pressure is applied to the proximal end of the proximal portion of the ureter, the ureter or opening in the proximal portion of the ureter. Such openings are not desirable because they can reduce the negative pressure in the distal portion of the ureteral catheter, thereby reducing the withdrawal or flow of fluid or urine from the kidney and renal pelvis. it is conceivable that. It is desirable that fluid flow from the ureter and / or kidney is not impeded by obstruction of the ureter and / or kidney by a catheter. Also, although not intended to be constrained by any theory, when negative pressure is applied to the proximal end of the proximal portion of the drainage lumen, the ureteral tissue becomes the proximal portion of the drainage lumen. It can be drawn into or into the opening along the opening, which is believed to be able to inflame the tissue.

Some embodiments of ureteral catheters with retaining portions with funnel-shaped supports according to the invention are shown in FIGS. 7A, 7B, 17, and 18A-41C. In FIGS. 7A-10E, the funnel-shaped support is formed by a coil of tubes. In FIG. 17-41C, another embodiment of the funnel-shaped support is shown. Each of these funnel-shaped supports according to the invention will be discussed in detail below.

Referring now to FIGS. 18A-D, in some embodiments, the distal portion 5004 of the ureteral catheter is shown, generally as 5000. The distal portion 5004 comprises a retention portion 5012 that constitutes the funnel-shaped support 5014. The funnel-shaped support 5014 comprises at least one side wall 5016. As shown in FIGS. 18C and 18D, the outer peripheral edge 1002 or the protective surface area 1001 comprises the outer surface or outer wall 5022 of the funnel-shaped support 5014. One or more drain holes, ports, or perforations, or internal openings 5030 are located on the protected surface area or inner surface area 1000 of the funnel-shaped support 5014. As shown in FIGS. 18C and 18D, there is a single outlet hole 5030 in the base portion 5024 of the funnel-shaped support, but there can be multiple holes.

At least one side wall 5016 of the funnel-shaped support 5014 comprises a first (outer) diameter D4 and a second (outer) diameter D5, the first outer diameter D4 being less than the second outer diameter D5. Is. The second outer diameter D5 of the funnel-shaped support 5014 is closer to the distal end 5010 of the distal portion 5004 of the drain lumen 5002 than the first outer diameter D4. In some embodiments, the first outer diameter D4 can range from about 0.33 mm to 4 mm (about 1 Fr to about 12 Fr (French catheter scale)) or about 2.0 ± 0.1 mm. In some embodiments, the second outer diameter D5 exceeds the first outer diameter D4 and can range from about 1 mm to about 60 mm, or about 10 mm to 30 mm, or about 18 mm ± 2 mm.

In some embodiments, at least one side wall 5016 of the funnel-shaped support 5014 can further comprise a third diameter D7 (shown in FIG. 18B), where the third diameter D7 is the second outer diameter. The diameter is less than D5. The third diameter D7 of the funnel-shaped support 5014 is closer to the distal end 5010 of the distal portion 5004 of the drain lumen 5002 than the second diameter D5. The third diameter D7 is discussed in more detail below with respect to the edges. In some embodiments, the third diameter D7 can range from about 0.99 mm to about 59 mm or from about 5 mm to about 25 mm.

At least one side wall 5016 of the funnel-shaped support 5014 comprises a first (inner) diameter D6. The first inner diameter D6 is closer to the proximal end 5017 of the funnel-shaped support 5014 than the third diameter D7. The first inner diameter D6 is less than the third diameter D7. In some embodiments, the first inner diameter D6 can range from about 0.05 mm to 3.9 mm or about 1.25 ± 0.75 mm.

In some embodiments, the total height H5 of the side wall 5016 along the central axis 5018 of the retention portion 5012 can range from about 1 mm to about 25 mm. In some embodiments, the height H5 of the sidewalls can vary at different parts of the sidewalls, for example, if the sidewalls have wavy or rounded edges as shown in FIG. 24. In some embodiments, the wavy portion can range from, or exceed, about 0.01 mm to about 5 mm, if desired.

In some embodiments, the funnel-shaped support 5014 can have a substantially conical shape, as shown in FIGS. 7A-10E and 17-41C. In some embodiments, the angle 5020 between the outer wall 5022 near the proximal end 5017 of the funnel-shaped support 5014 and the drain lumen 5002 adjacent to the base portion 5024 of the funnel-shaped support 5014 is about 100 degrees. It can range from about 180 degrees, or about 100 degrees to about 160 degrees, or about 120 degrees to about 130 degrees. The angle 5020 may vary at different positions around the circumference of the funnel-shaped support 5014, as shown in FIG. 22A, where the angle 5020 ranges from about 140 degrees to about 180 degrees.

In some embodiments, the edge or edge 5026 of the distal end 5010 of at least one side wall 5016 can be rounded, square, or any desired shape. The shapes defined by the edge 5026 are, for example, circular (as shown in FIGS. 18C and 23B), elliptical (as shown in FIG. 22B), leaf-shaped (as shown in FIGS. 28B, 29B, and 31). ), Square, rectangle, or any desired shape.

Here, with reference to FIGS. 28A-31, a funnel-shaped support 5300 is shown, at least one side wall 5302 comprising a plurality of leaf-shaped longitudinal folds 5304 along the length L7 of the side wall 5302. The outer peripheral edge 1002 or the protective surface area 1001 comprises the outer surface or outer wall 5032 of the funnel-shaped support 5300. One or more drain holes, ports, or perforations, or internal openings are located on the protected surface area or inner surface area 1000 of the funnel-shaped support 5300. As shown in FIG. 28B, there is a single drain hole at the base of the funnel-shaped support, but there can be multiple holes.

The number of folds 5304 can range from 2 to about 20 or about 6 as shown. In this embodiment, the folded portion 5304 is formed from one or more flexible materials such as silicone, polymer, solid material, fabric, or permeable mesh and can provide the desired leaf shape. The folded portion 5304 can have a substantially rounded shape, as shown in cross-sectional view 51B. The depth D100 of each fold 5304 at the distal end 5306 of the funnel-shaped support 5300 can be the same or variable and can range from about 0.5 mm to about 5 mm.

Here, with reference to FIGS. 29A and 29B, one or more folding portions 5304 may include at least one longitudinal support member 5308. The vertical support member 5308 can straddle the total length L7 or a part of the length L7 of the funnel-shaped support 5300. The longitudinal support member 5308 can be formed from a temperature sensitive shape memory material, such as a flexible but partially rigid material such as nitinol. The thickness of the longitudinal support member 5308 can range from about 0.01 mm to about 1 mm, if desired. In some embodiments, the nitinol frame can be coated with a suitable waterproof material such as silicone to form a tapered portion or funnel. In that case, the fluid is allowed to follow the inner surface 5310 of the funnel-shaped support 5300 and flow into the drain lumen 5312. In another embodiment, the fold 5304 is formed from a variety of rigid or partially rigid sheets or materials that are bent or molded to form a funnel-shaped retaining portion.

Referring now to FIGS. 30 and 31, the distal end or edge 5400 of the fold 5402 may comprise at least one edge support member 5404. The edge support member 5404 can span the entire circumference 5406 of the distal edge 5400 of the funnel-shaped support 5408 or one or more portions of the circumference 5406. The edge support member 5404 can be formed from a temperature sensitive shape memory material, such as a flexible but partially rigid material such as nitinol. The thickness of the edge support member 5404 can range from about 0.01 mm to about 1 mm, if desired.

In some embodiments as shown in FIGS. 18A-C, the distal end 5010 of the drainage lumen 5002 (or funnel-shaped support 5014) is, for example, a funnel-shaped support 5014 of about 0.01 mm to about 1 mm. It has an inwardly facing margin 5026 oriented towards the center of the funnel and can prevent inflammation of the kidney tissue. Thus, the funnel-shaped support 5014 can comprise a third diameter D7, which is less than a second diameter D5, where the third diameter D7 is a distal portion of the drain lumen 5002 from the second diameter D5. Close to the end 5010 of 5004. The outer surface 5028 of the edge 5026 can be a rounded, square edge, or any desired shape. Margin 5026 may assist in providing additional support to the renal pelvis and internal renal tissue.

Now with reference to FIGS. 24A-C, in some embodiments, the edge 5200 of the distal end 5202 of at least one side wall 5204 can be molded. For example, the edge 5200 can comprise a plurality of substantially rounded edges 5206 or a fan shape, eg, about 4 to about 20 or more rounded edges. The rounded edge 5206 provides a larger surface area than the straight edge and can help support the renal pelvis or kidney tissue and prevent obstruction. The edge 5200 can have any desired shape, but preferably has essentially no or no sharp edges to avoid injured tissue.

In some embodiments as shown in FIGS. 18A-C and 22A-23B, the funnel-shaped support 5014 comprises a base portion 5024 adjacent to the distal portion 5004 of the drain lumen 5002. The base portion 5024 is the internal lumen 5032 of the drainage lumen 5002 of the proximal portion 5006 of the drainage lumen 5002 to allow fluid flow into the internal lumen 5032 of the proximal portion 5006 of the drainage lumen 5002. It comprises at least one internal opening 5030 that is consistent with. In some embodiments, the cross section of the opening 5030 is circular, but the shape may vary, such as elliptical, triangular, square, etc.

In some embodiments as shown in FIGS. 22A-23B, the central axis 5018 of the funnel-shaped support 5014 is offset with respect to the central axis 5034 of the proximal portion 5006 of the drain lumen 5002. The offset distance X from the central axis 5018 of the funnel-shaped support 5014 with respect to the central axis 5034 of the proximal portion 5006 can range from about 0.1 mm to about 5 mm.

At least one internal opening 5030 of the base portion 5024 has a diameter D8 ranging from about 0.05 mm to about 4 mm (eg, shown in FIGS. 18C and 23B). In some embodiments, the diameter D8 of the internal opening 5030 of the base portion 5024 is approximately equal to the first inner diameter D6 of the adjacent proximal portion 5006 of the drainage lumen.

In some embodiments, the ratio of the height H5 of at least one side wall 5016 of the funnel-shaped support 5014 to the second outer diameter D5 of at least one side wall 5016 of the funnel-shaped support 5014 is from about 1:25. It reaches about 5: 1.

In some embodiments, at least one internal opening 5030 of the base portion 5024 has a diameter D8 ranging from about 0.05 mm to about 4 mm and a height H5 of at least one side wall 5016 of the funnel-shaped support 5014. The second outer diameter D5 of the funnel-shaped support 5014 ranges from about 1 mm to about 25 mm and from about 5 mm to about 25 mm.

In some embodiments, the thickness T1 of at least one side wall 5016 of the funnel-shaped support 5014 (eg, shown in FIG. 18B) is about 0.01 mm to about 1.9 mm or about 0.5 mm to about 1 mm. Can reach. The thickness T1 can be generally uniform throughout at least one side wall 5016, or may vary as desired. For example, the thickness T1 of at least one side wall 5016 can be thinner or thicker in the vicinity of the distal end 5010 of the distal portion 5004 of the drain lumen 5002 than the base portion 5024 of the funnel-shaped support 5014.

Referring here to FIG. 18A-21, along the length of at least one side wall 5016, the side wall 5016 is a straight line (as shown in FIGS. 18A and 20), a convex surface (as shown in FIG. 19), and a convex surface (as shown in FIG. 19). It can be concave (as shown in FIG. 21), or any combination thereof. As shown in FIGS. 19 and 21, the curvature of the side wall 5016 is approximated by the radius of curvature R from point Q so that the circles centered at Q meet the curve and have the same slope and curvature as the curve. Can be done. In some embodiments, the radius of curvature ranges from about 2 mm to about 12 mm. In some embodiments, the funnel-shaped support 5014 has a substantially hemispherical shape, as shown in FIG.

In some embodiments, at least one side wall 5016 of the funnel-shaped support 5014 is formed from the balloon 5100, for example, as shown in FIGS. 35A, 35B, 38A, and 38B. The balloon 5100 can have any shape that provides a funnel-shaped support and blocks the remaining obstruction of the ureter, renal pelvis, and / or kidney. As shown in FIGS. 35A and 35B, the balloon 5100 has the shape of a funnel. The balloon can be inflated after insertion or contracted before removal by adding or removing gas or air through the gas port 5102. The gas port 5102 can simply be continuous with the inner 5104 of the balloon 5100, for example the balloon 5100 is adjacent to the inner 5106 or the outer 5108 of the adjacent portion of the proximal portion 5006 of the drain lumen 5002. Can be surrounded. The diameter D9 of the side wall 5110 of the balloon 5100 can range from about 1 mm to about 3 mm, with the side walls tapering or proximal to the distal end 5112 of the funnel-shaped support 5116 having a uniform diameter. It can vary along its length so as to taper towards the end 5114. The outer diameter D10 of the distal end 5112 of the funnel-shaped support 5116 can range from about 5 mm to about 25 mm.

In some embodiments, at least one side wall 5016 of the funnel-shaped support 5014 is continuous along a height H5 of at least one side wall 5016, for example, as shown in FIGS. 18A, 19, 20, and 21. do. In some embodiments, at least one side wall 5016 of the funnel-shaped support 5014 comprises a solid wall, for example, the side wall 5016 is not through the side wall 24 hours after contact with fluid such as urine on one side. It is permeable.

In some embodiments, at least one side wall of the funnel-shaped support is intermittent along the height or body of at least one side wall. As used herein, "intermittent" means that at least one side wall allows fluid or urine to flow through it, for example by gravity or negative pressure, into the drainage lumen. It means to have one opening. In some embodiments, the opening can be a conventional opening through a side wall, or an opening in a mesh material, or an opening in a permeable fabric. The cross-sectional shape of the opening can be circular or non-circular, such as rectangular, square, triangular, polygonal, or elliptical, if desired. In some embodiments, the "opening" is the gap between adjacent coils within the retention portion of the catheter, comprising a coiled tube or conduit.

As used herein, "opening" or "hole" means a continuous void space or channel through the sidewall from the outside to the inside or vice versa. In some embodiments, the at least one opening can have an area that can be the same or different, and can range from about 0.002 mm ² to about 100 mm ² or about 0.002 mm ² to about 10 mm ² . As used herein, the "area" or "surface area" or "cross-sectional area" of an opening means the smallest or minimal plane area defined by the perimeter of the opening. For example, the opening is circular and has a diameter of about 0.36 mm (area of 0.1 mm ² ) on the outside of the sidewall, but only 0.05 mm in diameter (area of 0.002 mm ² ) inside the sidewall. Or if held at a point on the opposite side of the side wall, the "area" would be 0.002 mm ² because it is the minimum or minimal plane area for flow through the openings in the side wall. If the opening is square or rectangular, the "area" will be the length x the width of the plane area. For any other shape, the "area" can be determined by conventional mathematical calculations well known to those of skill in the art. For example, the "area" of an irregularly shaped opening is found by adapting the shape to fill the planar area of the opening, calculating the area of each shape, and adding the areas of each shape together.

In some embodiments, at least a portion of the sidewall comprises at least one (one or more) openings. In general, the central axis of the opening can be approximately perpendicular to the planar outer surface of the sidewall, or the opening can be angled with respect to the planar outer surface of the sidewall. The dimensions of the bore of the opening may be uniform throughout its depth, or the width may be increased, decreased, or alternated through the opening from the outer surface of the sidewall to the inner surface of the sidewall. Depending on any of the above, it may fluctuate along the depth.

Referring here to FIGS. 9A-9E, 10A, 10E, 11-14, 27, 32A, 32B, 33, and 34, in some embodiments, at least a portion of the sidewall is at least one (one or more). ) Provide an opening. The opening can be located anywhere along the side wall. For example, the openings are uniformly positioned throughout the side wall, or within a defined area of the side wall, such as closer to the distal end of the side wall, or closer to the proximal end of the side wall, or the length or circumference of the side wall. Can be positioned vertically or horizontally or within a random group along. Not intended to be constrained by any theory, but directly to the ureter, renal pelvis, and / or other kidney tissue when negative pressure is applied to the proximal end of the proximal portion of the drainage lumen. An opening in the proximal portion of the adjacent, funnel-shaped support reduces negative pressure in the distal portion of the ureteral catheter, thereby reducing fluid or urine withdrawal or flow from the renal pelvis. Such openings are considered undesired, as they can cause and possibly inflame the tissue.

The number of openings can vary from 1 to 1000 or more, if desired. For example, in FIG. 27, six openings (three on each side) are shown. As discussed above, in some embodiments, the at least one opening can be the same or different, respectively, and can range from about 0.002 mm ² to about 50 mm ² or about 0.002 mm ² to about 10 mm ² . , Can have an area.

In some embodiments, as shown in FIG. 27, the opening 5500 can be located closer to the distal end 5502 of the side wall 5504. In some embodiments, the opening is located within the distal half 5506 of the sidewall towards the distal end 5502. In some embodiments, the openings 5500 are evenly distributed around the circumference of the distal half 5506 or even closer to the distal end 5502 of the side wall 5504.

In contrast, in FIG. 32B, the opening 5600 is located near the proximal end 5602 of the inner side wall 5604 and does not come into direct contact with the tissue because the outer side wall 5606 is between the opening 5600 and the tissue. Alternatively, or in addition, one or more openings 5600 can be located near the distal end of the medial sidewall, if desired. The inner side wall 5604 and the outer side wall 5606 can be connected by one or more supports 5608 or ridges that connect the outer 5610 of the inner side wall 5604 to the inner 5612 of the outer side wall 5606.

9A-9E, 10A, 10D-10G, 18B, 18D, 18E, 20, 22A, 22B, 23A, 23B, 24A-24C, 25, 26, 27, 28A, 28B, 29A-29C, 30, 31, 32A. , 32B, 33, 34, 35A, 35B, 37B, 38A, 39B, 39C, 40A-40C, and 41A-41C, in some non-limiting examples, protected surface area or inner surface area. 1000 can be established with a variety of different shapes or materials. Non-limiting examples of protected surface area or inner surface area 1000 are, for example, internal portions 152, 5028, 5118, 5310, 5410 of funnels 150, 5014, 5116, 5300, 5408, 5508, 5614, 5702, 5802, 6000. , 5510, 5616, 5710, 5814, 6004, coil 183, 184, 185, 187, 334, 1280, 1282, 1284 internal parts 164, 166, 168, 170, 338, 1281, 1283, 1285, porous material 5900. , 6002 internal parts 5902, 6003, mesh 57, 5704, 5804 internal parts 162, 5710, 5814, or cage 530 internal parts 536 with protected drain holes 533.

In some non-limiting examples, at least one protected drain hole, port, or perforation 133, 1233 is placed on the protected surface area 1000. Depending on the application of negative pressure therapy through the catheter, the urothelium or mucosal tissues 1003, 1004 of the retention portions 130, 330, 410, 500, 1230, 1330, 2230, 3230, 4230, 5012, 5013 of the catheter. Of the protected drain holes, ports, or perforations 133, 1233 that are coloneized or crushed onto the outer peripheral edge 189, 1002 or protected surface area 1001 and thereby placed on the protected surface area or inner surface area 1000. Prevents or prevents obstruction of one or more of the, thereby allowing the patency fluid column or flow to the renal pelvis and calyx and drainage lumen 124,324,424,524,1224,5002, Established, maintained, or improved between 5003, 5312, 5708, and 5808.

In some embodiments, the retaining portions 130, 330, 410, 500, 1230, 1330, 2230, 3230, 4230, 5012, 5013 have an outward facing side 1288 and an inward facing side 1286. It comprises one or more spiral coils, the outer peripheral edge 1002 or the protective surface area 1001 comprises an outward facing side 1288 of the one or more spiral coils, and at least one protected drain hole, port, or perforation. 133, 1233 are located on the inwardly facing side 1286 (protected surface area or inner surface area 1000) of one or more spiral coils.

For example, the funnel shape as shown in FIG. 25 can form a side wall 5700 that conforms to the natural anatomical shape of the renal pelvis and prevents the urothelium from contracting the fluid column. The interior 5710 of the funnel-shaped support 5702 provides a protected surface area 1000 through which the fluid column has an opening 5706 that provides a passage through which the fluid column can flow from the calyx into the drain lumen 5708. .. Similarly, the mesh morphology of FIG. 26 can also generate a protected surface area 1000, such as the interior 5814 of the mesh 5804, between the calyx and the drainage lumen 5808 of the catheter. The mesh 5704, 5804 comprises a plurality of openings 5706, 5806 to allow fluid flow through it into the drain lumen 5708, 5808. In some embodiments, the maximum area of the opening is less than about 100 mm ² , or less than about 1 mm ² , or about 0.002 mm ² to about 1 mm ² , or about 0.002 mm ² to about 0.05 mm ² . be able to. The mesh 5704, 5804 can be formed from any suitable metal or polymer material as discussed above.

In some embodiments, the funnel-shaped support further comprises a cover portion over the distal end of the funnel-shaped support. The cover portion can be formed as an integral part of the funnel-shaped support or connected to the distal end of the funnel-shaped support. For example, as shown in FIG. 26, the funnel-shaped support 5802 traverses the distal end 5812 of the funnel-shaped support 5802 and projects a cover portion 5810 from the distal end 5812 of the funnel-shaped support 5802. Be prepared. The cover portion 5810 can have any desired shape such as flat, convex, concave, wavy, and combinations thereof. The cover portion 5810 can be formed from a mesh or any polymeric solid material, as discussed above. The cover portion 5810 can provide an outer peripheral edge 1002 or a protective surface area 1001 to support the flexible tissue within the renal region and assist in promoting urine production.

In some embodiments, the funnel-shaped support comprises a porous material, for example, as shown in FIGS. 39A-40C. FIGS. 39A-40C and suitable porous materials are discussed in detail below. Briefly, in FIGS. 39 and 40, the porous material itself is a funnel-shaped support. In FIG. 39, the funnel-shaped support is a wedge of porous material. In FIG. 40, the porous material is in the shape of a funnel. In some embodiments, such as FIG. 33, the porous material 5900 is located within the interior 5902 of the side wall 5904. In some embodiments, such as FIG. 34, the funnel-shaped support 6000 comprises a porous liner 6002 located adjacent to the interior 6004 of the side wall 6006. The thickness T2 of the porous liner 6002 can range from, for example, about 0.5 mm to about 12.5 mm. The area of the opening in the porous material can be from about 0.002 mm ² to about 100 mm ² or less.

Referring here to FIGS. 37A and 37B, for example, the retention portion 130 of the ureteral catheter 112 is configured to be located in the patient's renal pelvis and / or kidney in some embodiments, dilatation and /. Alternatively, it comprises a catheter tube 122 having a tapered distal end portion. For example, the retention portion 130 comprises an outer surface 185 configured to be positioned relative to the ureter and / or kidney wall and an inner configured to direct fluid towards the drainage lumen 124 of the catheter 112. It can be a funnel-shaped structure with a surface 186. The retaining portion can be configured as a funnel-shaped support having an outer surface 185 and an inner surface 186, the outer peripheral edge 189 or the protective surface area 1001 comprising the outer surface 185 of the funnel-shaped support, one. The drain holes, ports, or holes 133, 1233 described above are arranged on the inner surface 186 at the base of the funnel-shaped support. In another embodiment shown in FIGS. 32A and 32B, the retention portion can be configured with a funnel-shaped support 5614 having an outer surface 185 and an inner surface 5616, the outer peripheral edge 1002 or the protective surface area 1001. , With an outer surface of the outer side wall 5606. The protected surface area 1000 can comprise the inner side wall 5604 of the inner funnel, and one or more drain holes, ports, or perforations 5600 can be located on the inner side wall 5604 of the funnel-shaped support.

Referring to FIGS. 37A and 37B, the retention portion 130 is adjacent to the distal end of the drainage lumen 124 and has a first diameter D1 with a proximal end 188 and when the retention portion 130 is in its unfolded position. It can be equipped with a distal end 190 having a second diameter D2 above the first diameter D1. In some embodiments, the retention portion 130 is capable of transitioning from a crushed or compressed position to an expanded position. For example, the retention portion 130 is attached radially outward so that when the retention portion 130 is advanced to its fluid collection position, the retention portion 130 (eg, the funnel portion) expands radially outwardly. Can be struck.

The retention portion 130 of the ureteral catheter 112 can be made of a variety of suitable materials capable of transitioning from a crushed state to a deployed state. In one embodiment, the retention portion 130 comprises a framework of a forked or elongated member formed from a temperature sensitive shape memory material such as nitinol. In some embodiments, the nitinol frame can be coated with a suitable waterproof material such as silicone to form a tapered portion or funnel. In that case, the fluid is allowed to flow into the drain lumen 124 following the inner surface 186 of the retention portion 130. In another embodiment, the retention portion 130 is formed from various rigid or partially rigid sheets or materials that are bent or molded to form a funnel-shaped retention portion, as illustrated in FIGS. 37A and 37B. Will be done.

In some embodiments, the retention portion of the ureteral catheter 112 may include one or more mechanical stimulation devices 191 to provide stimulation to nerves and muscle fibers in adjacent tissues of the ureter and renal pelvis. can. For example, the mechanical stimulation device 191 can include a linear or annular actuator embedded in or adjacent to a portion of the sidewall of the catheter tube 122 and configured to emit low levels of vibration. .. In some embodiments, mechanical stimulation is provided to the ureter and / or part of the renal pelvis and can complement or modify the therapeutic effects obtained by applying negative pressure. Although not intended to be constrained by theory, such stimuli are adjacent, for example, by stimulating the nerves associated with the ureter and / or the renal pelvis, and / or by activating the peristaltic muscles. It is thought to affect the organization that does. Nerve stimulation and muscle activation can result in changes in pressure gradients or pressure levels within surrounding tissues and organs, which, if any, contribute to the therapeutic benefits of negative pressure therapy. Can be improved.

Referring to FIGS. 38A and 38B, according to another embodiment, the retention portion 330 of the ureteral catheter 312 is formed within the inflatable element or balloon 350 located proximal to the spiral structure 332 and the spiral structure 332 and is formed in the renal pelvis. And / or a catheter tube 322 having a distal portion 318 to provide additional retention within the fluid collection site. The balloon 350 is sufficient to retain the balloon in the renal pelvis or urinary tract, but can be inflated to a pressure low enough to avoid swelling or damage to these structures. Suitable expansion pressures are known to those of skill in the art and can be easily determined by trial and error. As in the previous embodiment, the helical structure 332 can be imparted by bending the catheter tube 322 to form one or more coils 334. The coil 334 can have a constant or variable diameter and height as described above. The catheter tube 322 is further located on the side wall of the catheter tube 322 and urine is drawn into the drainage lumen 324 of the catheter tube 322, eg, the inwardly facing side and / or the outward facing side of the coil 334. It comprises a plurality of drain ports 336 that allow it to be directed from the body through the drain lumen 324 on the side of the urine.

As shown in FIG. 38B, the inflatable element or balloon 350 can comprise, for example, an annular balloon-like structure having a substantially heart-shaped cross section and comprising a surface or cover 352 defining a cavity 353. The cavity 353 fluidly communicates with an inflatable lumen 354 extending parallel to the drain lumen 324 defined by the catheter tube 322. The balloon 350 is inserted into the tapered portion of the renal pelvis and is configured to be inflated so that its outer surface 356 contacts and rests against the ureter and / or the inner surface of the renal pelvis. .. The inflatable element or balloon 350 can comprise a tapered inner surface 358 extending longitudinally and radially inwardly toward the catheter tube 322. The medial surface 358 can be configured to direct urine towards the catheter tube 322 so that it is drawn into the drainage lumen 324. The inner surface 358 can also be positioned to prevent fluid from accumulating in the urinary tract, such as around an inflatable element or the periphery of the balloon 350. The inflatable retaining portion or balloon 350 is preferably sized to fit within the renal pelvis and can have a diameter ranging from about 10 mm to about 30 mm.

With reference to FIGS. 39A-40C, in some embodiments, an assembly 400 comprising a ureteral catheter 412 with a retention portion 410 is illustrated. The retention portion 410 is formed of a porous and / or spongy material attached to the distal end 421 of the catheter tube 422. The porous material can be configured to carry and / or absorb urine and direct urine towards the drain lumen 424 of the catheter tube 422. The retention portion 410 can be configured as a funnel-shaped support having an outer surface and an inner surface, and the outer peripheral edge 1002 or the protective surface area 1001 comprises the outer surface of the funnel-shaped support and is within the porous material. One or more drain holes, ports, or perforations can be placed within the porous material or on the inner surface 426 of the funnel-shaped support.

As shown in FIG. 40, the retention portion 410 can be a porous wedge-shaped structure configured for insertion and retention in the patient's renal pelvis. The porous material comprises multiple pores and / or channels. The fluid can be drawn through the channels and holes, for example by gravity or in response to the induction of negative pressure through the catheter 412. For example, fluid can enter the wedge-shaped retention section 410 through the pores and / or channels and drain, for example, by capillarity, peristalsis, or as a result of the induction of negative pressure within the pores and / or channels. It is pulled out towards the distal opening 420 of the lumen 424. In another embodiment, as shown in FIG. 40, the retention portion 410 comprises a hollow funnel structure formed from a porous sponge-like material. As indicated by arrow A, the fluid follows the inner surface 426 of the funnel structure and is directed into the drain lumen 424 defined by the catheter tube 422. The fluid can also enter the funnel structure of the retention portion 410 through the holes and channels in the porous sponge-like material of the sidewall 428. For example, suitable porous materials can include open cell polyurethane foams such as polyurethane ethers. Suitable porous materials also have, for example, with or without antibacterial additives such as silver and with or without additives for modifying material properties such as hydrogels, hydrophilic colloids, acrylics, or silicones. It can include a laminate of layers of woven or non-woven fabric, including polyurethane, silicone, polyvinyl alcohol, cotton, or polyester.

Referring to FIG. 41, according to another embodiment, the retention portion 500 of the ureteral catheter 512 comprises an expandable cage 530. The expandable cage 530 comprises one or more longitudinally and radially extending hollow tubes 522. For example, tube 522 can be formed from an elastic shape memory material such as nitinol. The cage 530 is configured to transition from a contracted state for insertion through the patient's urinary tract to an expanded state for positioning within the patient's ureter and / or kidney. The hollow tube 522 comprises a plurality of discharge ports 534 that may be located on the tube, eg, its radial inward facing side. Port 534 is configured to allow fluid to flow or be drawn through the port 534 into a separate tube 522. The fluid is drained through the hollow tube 522 into the drainage lumen 524 defined by the catheter body 526 of the ureteral catheter 512. For example, the fluid can flow along the path indicated by arrow 532 in FIG. In some embodiments, when negative pressure is induced in the renal pelvis, kidney, and / or ureter, the ureteral wall and / or part of the renal pelvis is directed against the outwardly facing surface of the hollow tube 522. Can be towed. The drain port 534 is positioned and configured so that it is not significantly obstructed by the ureteral structure in response to the application of negative pressure to the ureter and / or kidney.

In some embodiments, a ureteral catheter, including a funnel-shaped support, uses a conduit through the urethra into the bladder into the patient's urinary tract, more specifically the renal pelvis region / kidney. Can be deployed within. The funnel-shaped support 6100 is in a crushed state (shown in FIG. 36) and is placed in the ureteral sheath 6102. To deploy a ureteral catheter, the healthcare professional will insert a cystoscope into the urethra and provide a channel for the tool to enter the bladder. The ureter is visualized and the guidewire will be inserted through the cystoscope and ureter until the tip of the guidewire reaches the renal pelvis. The cystoscope will potentially be removed and a "pusher tube" will be sent over the guide wire to the renal pelvis. The guide wire will be removed while the "pusher tube" remains in place and acts as a deployable sheath. The ureteral catheter is inserted through the pusher tube / sheath and the catheter tip will be activated once it extends beyond the end of the pusher tube / sheath. The funnel-shaped support will expand radially and take an unfolded position.
Exemplary ureteral stents:

Here with reference to FIG. 1A, in some embodiments, the ureteral stents 52, 54 have a proximal end 62, a distal end 58, a vertical axis, and a vertical axis from the proximal end to the distal end. It comprises an elongated body that extends along and has at least one drainage channel that maintains the patency of fluid flow between the patient's kidney and bladder. In some embodiments, the ureteral stent further comprises a pigtail coil or loop over at least one of the proximal or distal ends. In some embodiments, the body of the ureteral stent further comprises at least one perforation on its side wall. In other embodiments, the body of a ureteral stent has essentially no or no perforation on its side wall.

Some examples of ureteral stents 52, 54 that may be useful in this system and method include CONTOUR ^TM ureteral stents, CONTOUR VL ^TM ureteral stents, POLARIS ^TM loop ureteral stents, POLARIS ^TM ultra ureteral stents. , PERCUFLEX ^TM ureteral stent, PERCUFLEX ^TM plus ureteral stent, STRETCH ^TM VL flexima ureteral stent, each of which is commercially available from Boston Scientific Corporation (Natick, Massachusetts). Boston Scientific Corp. See the publication (July 2010), "Ureteral Stent Portfolio" (incorporated herein by reference). CONTOUR ^TM and CONTOUR VL ^TM ureteral stents are constructed from a soft Percuflex ^TM material that is softened at body temperature and designed for an indwelling time of 365 days. Variable length coils on the distal and proximal ends allow one stent to fit different urinary tract lengths. Fixed length stents can be 6F-8F with lengths ranging from 20 cm to 30 cm, and variable length stents can be 4.8F-7F with lengths ranging from 22-30 cm. Other examples of suitable ureteral stents are INLAY® ureteral stents, INLAY® OPTIMA® ureteral stents, BARDEX® double pigtail ureteral stents, and FLOORO-. 4 ^TM silicone ureteral stents, including C.I. R. Bard, Inc. (Murray Hill, NJ) is commercially available. "Ureteral Stents", http: // www. birdmedical. com / products / kidney-stone-management / ureteral-stations / (January 21, 2018) (incorporated herein by reference).

Stents 52, 54 can be optionally deployed within one or both kidneys or kidney area of the patient (renal pelvis or ureter adjacent to the renal pelvis). Typically, these stents insert a stent with a nitinol wire through it into the kidney through the urethra and bladder, then remove the nitinol wire from the stent, allowing the stent to be deployed. Expanded by. Many of the above stents have planar loops 58, 60 on the distal end (because they are deployed in the kidney), and some also have planar loops 62, 64 on the proximal end of the stent. It has in the bladder and is deployed in the bladder. When the nitinol wire is removed, the stent takes a pre-stressed planar loop shape at the distal and / or proximal end. To remove the stent, a nitinol wire is inserted to straighten the stent and the stent is removed from the ureter and urethra.

Other examples of suitable ureteral stents 52, 54 are disclosed in PCT Patent Application Publication No. WO 2017/019974 (incorporated herein by reference). In some embodiments, the ureteral stent 100, for example, as shown in FIG. 1-7 of WO2017 / 019974 and FIG. 3 of the present specification (identical to FIG. 1 of WO2017 / 0199774). Is the proximal end 102, the distal end 104, the vertical axis 106, the outer surface 108, and the inner surface 110, extending along the vertical axis 106 from the proximal end 102 to the distal end 104. Can include an elongated body 101 with an inner surface 110 defining a deformable bore 111 and at least two fins 112 projecting radially away from the outer surface 108 of the body 101. The deformable bore 111 has (a) a default orientation 113A (shown to the left in FIG. 59) with an open bore 114 defining a longitudinally open channel 116, and (b) essentially closed longitudinally. With a second orientation 113B (shown to the right in FIG. 59) with at least an essentially closed bore 118 or a closed bore defining the discharge channel 120 along the vertical axis 106 of the extension body 101. The deformable bore 111 is movable from the default orientation 113A to the second orientation 113B in response to the radial compressive force 122 applied to at least a portion of the outer surface 108 of the body 101.

In some embodiments, as shown in FIG. 3, the drainage channel 120 of the ureteral stent 100 has a diameter D, which causes the deformable bore 111 to move from the default orientation 113A to the second orientation 113B. The diameter can be reduced to a point above where urine flow through the deformable bore 111 would be reduced. In some embodiments, the diameter D is reduced by up to about 40% as the deformable bore 111 moves from the default orientation 113A to the second orientation 113B. In some embodiments, the diameter D at the default orientation 113A can range from about 0.75 to about 5.5 mm, or about 1.3 mm, or about 1.4 mm. In some embodiments, the diameter D in the second orientation 113B can range from about 0.4 to about 4 mm or about 0.9 mm.

In some embodiments, the one or more fins 112 include a flexible material that is soft to medium soft based on the Shore hardness scale. In some embodiments, the body 101 comprises a flexible material that is medium hard to hard based on the Shore hardness scale. In some embodiments, the one or more fins have a hardness of about 15A to about 40A. In some embodiments, the body 101 has a hardness of about 80A to about 90A. In some embodiments, the one or more fins 112 and the body 101 include, for example, a flexible material having a hardness of about 40 A to about 70 A, which is medium soft to medium hard based on the Shore hardness scale.

In some embodiments, the one or more fins 112 and the body 101 include, for example, a flexible material having a hardness of about 85 A to about 90 A, which is medium hard to hard based on the Shore hardness scale.

In some embodiments, the default orientation 113A and the second orientation 113B support fluid or urine flow through the deformable bore 111 as well as around the outer surface 108 of the stent 100.

In some embodiments, the one or more fins 112 extend longitudinally from the proximal end 102 to the distal end 104. In some embodiments, the stent has two, three, or four fins.

In some embodiments, the outer surface 108 of the body has an outer diameter ranging from about 0.8 mm to about 6 mm or about 3 mm in the default orientation 113A. In some embodiments, the outer surface 108 of the body has an outer diameter ranging from about 0.5 mm to about 4.5 mm or about 1 mm in the second orientation 113B. In some embodiments, the one or more fins have a width or tip ranging from about 0.25 mm to about 1.5 mm or about 1 mm and project from the outer surface 108 of the body substantially perpendicular to the vertical axis. ..

In some embodiments, the radial compressive force is provided by at least one of normal ureteral physiology, abnormal ureteral physiology, or application of any external force. In some embodiments, the ureteral stent 100 intentionally adapts to a dynamic ureteral environment, the ureteral stent 100 having a proximal end 102, a distal end 104, a vertical axis 106, and the outside. An elongated body 101 comprising a surface 108 and an inner surface 110 that defines a deformable bore 111 that is an inner surface 110 and extends along a vertical axis 106 from the proximal end 102 to the distal end 104. The deformable bore 111 comprises (a) a default orientation 113A comprising an open bore 114 defining a longitudinally open channel 116 and (b) at least defining a longitudinally essentially closed channel 120. The deformable bore comprises a second orientation 113B with an essentially closed bore 118, depending on that a radial compressive force 122 is applied to at least a portion of the outer surface 108 of the body 101. The inner surface 110 of the body 101 is movable from the default orientation 113A to the second orientation 113B, which causes the deformable bore 111 to move from the default orientation 113A to the second orientation 113B. The diameter can be reduced to a point above where the fluid flow through the deformable bore 111 would be reduced. In some embodiments, the diameter D is reduced by up to about 40% as the deformable bore 111 moves from the default orientation 113A to the second orientation 113B.

Other examples of suitable ureteral stents are disclosed in US Patent Application Publication No. US2002 / 0138353A1 (incorporated herein by reference). In some embodiments, for example, the same as FIGS. 4, 5, and 7 of US 2002/0183853A1 and FIGS. 1, 4, 5, and 7 of US 2002/0183853A1. As shown in), the ureteral stent has a proximal end 12, a distal end 14 (not shown), a vertical axis 15 and a vertical axis 15 from the proximal end 12 to the distal end 14. At least one drainage channel (eg, 26, 28, 30, FIG. 5, 32, 34, FIG. 5) that extends along and maintains the patency of fluid flow between the patient's kidney and bladder. It comprises an extension body 10 comprising 36 and 38, 48) in FIG. In some embodiments, the at least one discharge channel is partially open along at least its longitudinal portion. In some embodiments, at least one discharge channel is closed along at least its longitudinal portion. In some embodiments, at least one discharge channel is closed along its longitudinal length. In some examples, the ureteral stent is radial compressible. In some embodiments, the ureteral stent is radially compressible, narrowing at least one drain channel. In some embodiments, the extension body 10 comprises at least one external fin 40 along the vertical axis 15 of the extension body 10. In some embodiments, the extension body comprises 1 to 4 discharge channels. The diameter of the discharge channel can be the same as that described above.
Coated and / or impregnated catheter or stent device

In some embodiments, at least some or all of the devices, such as any of the catheters and / or stents described herein, are at least of the coating / impregnating materials described herein. One can be coated and / or impregnated. Generally, with reference to FIGS. 1A-1W, 2A-14, 17-41C, 52A-54, and 56-57, are described herein collectively designated as 7010, generally such as a catheter or stent. Any part or all of the devices can be coated and / or impregnated with at least one of the coating / impregnating materials described herein.

In some embodiments, the device 7010 can be configured to facilitate insertion and / or removal of the coated device 7010 in the patient's urinary tract 1 and / or once inserted. , At least one coating and / or impregnation 7022 can improve the functionality of the device 7010. The device 7010 can be configured for insertion into one or more of the patient's bladder, ureter, renal pelvis, and / or kidney. The device 7010 can be deployed to maintain the end 7044 or retention portion 7020 of the device 7010 at a desired location within the urinary tract 1. The device 7010 can be sized to fit tightly at the desired location within the urinary tract 1, as described in detail herein. The device 7010 can be narrow enough in the retracted state so that the coated device 7010 can be easily inserted and removed. The device 7010 can have any of the configurations described herein, eg, a catheter or a stent. Non-limiting examples of suitable catheters and stents are disclosed herein and are shown in FIGS. 1A-1W, 2A-14, 17-41C, 52A-54, and 56-57. In some embodiments, a suitable catheter retention portion 7020 comprises a funnel, coil, balloon, cage, sponge, and / or a combination thereof.

The device 7010 to be coated and / or impregnated is copper, silver, gold, nickel-titanium alloy, stainless steel, titanium, and / or polyurethane, polyvinyl chloride, polytetrafluoro, as discussed in detail above. Ethethylene (PTFE), latex, silicon coated latex, silicone, polyglycolide or poly (glycolic acid) (PGA), polylactic acid (PLA), poly (lactic acid-co-glycolic acid), polyhydroxyalkanoic acid, polycaprolactone And / or can be formed or contained from at least one device material, including at least one of biocompatible polymers such as poly (propylene fumarate).

In some embodiments, at least one coating and / or impregnation 7022 causes mucosal tissue 1003 to occlude at least one protected drain hole, port, or perforation 7036 in response to the application of negative pressure through the catheter. It may be present on and / or at least on and / or at least the outer peripheral edges 72, 1002 or the protective surface areas 1001, 7038 of the device 7010, which prevents it from being prevented. In some embodiments, the at least one coating and / or impregnation 7022 may be present on and / or within any portion of the device 7010 and / or on and / or within the entire device 7010. In some embodiments, the at least one coating and / or impregnation 7022 may be present on and / or within at least a portion of the retention portion 7020, or on or within the entire retention portion 7020. In some embodiments, the at least one coating and / or impregnation 7022 may be present on and / or within at least a portion of the surface of the device, or on and / or within the entire surface of the device. In some embodiments, the at least one coating and / or impregnation 7022 may be present on and / or within at least the outer surface 7028 of the device, or on and / or across the outer surface 7028 of the device. In some embodiments, the at least one coating and / or impregnation 7022 is on and / or other parts of the device 7010, such as some or all of the delivery catheters of any of the catheter assemblies described above. Can exist within. In some embodiments, the at least one coating and / or impregnation 7022 does not significantly or substantially affect the flexibility of the coating and / or impregnated device 7010. Formed from material.

In some embodiments, the at least one coating 7022 can comprise one or more coatings, such as 1-10 coatings, 2-4 coatings. In some embodiments, the material on which the device 7010 is formed (device material discussed herein) may be coated with at least one of the coating / impregnating materials discussed herein. can. It is understood that the coating 7022 is considered as a possibility that the components of one coating layer may migrate into one or more adjacent or adjacent layers and / or into a surface or into the device 7010. Then, it may be applied or formed in the layer.

In some embodiments, the material on which the device 7010 is formed (device material discussed herein) may be impregnated with at least one of the coating / impregnating materials discussed herein. can. As used herein, "impregnated" means that at least a portion of the coating / impregnating material discussed herein is under the outer surface of the device material on which the device 7010 is formed. / Or means to penetrate at least part of it. In some embodiments, different coating / impregnating materials and / or different amounts of individual coating / impregnating materials discussed herein may be used to impregnate different parts or regions of the device 7010. can. For example, the retention portion 7020 can be impregnated with at least one of the coating / impregnating materials described herein, such as at least one lubricating material and / or at least one antibacterial material, while discharging. The tube is impregnated with at least one antibacterial material. Some or all of the device 7010 can be impregnated and / or coated, if desired. In some embodiments, there may be different layers of impregnation at different depths within the device 7010.

The at least one coating / impregnating material (which may be used as a coating material and / or an impregnating material, referred to as "coating / impregnating material" for brevity) is a lubricant, antibacterial material, pH buffer, or. Includes at least one (one or more) of anti-inflammatory materials. In some embodiments, at least one coating and / or impregnation 7022 improves short-term or long-term performance of the device 7010, reduces pain during insertion / removal of the device 7010 into the urinary tract, and. / Or can be used to mitigate the risks associated with long-term use of indwelling devices.

For example, at least a portion of the device 7010 can be coated and / or impregnated with at least one coating / impregnating material, including at least one lubricant. The at least one coating and / or impregnated 7022 containing at least one lubricant has a lower coefficient of friction than, for example, a coated / unimpregnated device, acts as a lubricant, and / or such as moisture or urine. It can be lubricated or slippery in the presence of fluid. The presence of lubricant in at least one coating and / or impregnation 7022 may make the device 7010 easier to deploy and remove. In general, in some embodiments, the at least one coating and / or impregnation 7022 can include materials configured to address the causes of problems and discomfort associated with indwelling catheters.

Alternatively, or in addition, the device 7010 can be coated and / or impregnated with at least one of an antibacterial material, a pH buffer, and / or an anti-inflammatory material. At least one of the antibacterial material, pH buffer, and / or anti-inflammatory material is tissue inward growth through part of the device, when part of the device comes into contact with the surrounding fluid and / or tissue. It can mitigate the risks associated with long-term use of indwelling catheters such as foreign body reactions caused by, infection of the tissue surrounding the device, and / or formation of a jacket on a portion of the device. The coat can be caused, for example, by protein adsorption and / or accumulation of minerals or urinary crystals.

In some embodiments, the at least one coating and / or impregnation 7022 comprises at least one lubricant. In some embodiments, the outer surface or layer of at least one coating and / or impregnation 7022 comprises at least one lubricant. Lubricating coatings / impregnations have one or more outer layers having a degree of lubrication or coefficient of kinetic friction, or an outer layer having a coefficient of kinetic friction that exceeds the coefficient of kinetic friction of uncoated or equivalent devices coated with lubricant. It can be explained in terms of the amount of friction reduction provided as compared to the device with coating / impregnation. The coefficient of dynamic friction can be determined using ASTM method D1894-14 (March 2014). A rigid mandrel is determined to minimize the amount of contraction that occurs in the open space inside the stent / catheter medial lumen and any potential consequences of the medial lumen as the thread is dragged along the material. It can be inserted through the inner lumen of the stent / catheter segment being dimensioned and examined. Alternatively, the catheter tube can be stripped and opened into a flat sheet for examination.

In some embodiments, the lubricant can include at least one hydrophilic lubricating material. Exemplary hydrophilic lubricating materials are polyethylene glycol, polyvinylpyrrolidone, polytetrafluoroethylene, polyvinyl alcohol, polyacrylamide, polymethacrylic acid, and copolymers of other acrylic polymers or materials listed above, or polyelectrolytes. Includes at least one (one or more) of them. An exemplary hydrophilic coating material / impregnation is described in Koninklijke DSM N. et al. V. ComfortCoat® Polymer Electrolyte-Containing Hydrophilic Coating, available from. Examples of suitable hydrophilic coating / impregnating materials, including polyelectrolytes, are disclosed in US Pat. No. 8,512,795 (incorporated herein by reference).

In some embodiments, the at least one coating / impregnation 7022 can include at least one non-hydrophilic material. For example, one or more layers of at least one coating and / or impregnated 7022 may be polytetrafluoroethylene (eg, Teflon®), siloxane, silicone or polysiloxane, or other slippery and / or low friction. Can contain or be formed of material.

In some embodiments, the lubricant can include at least one polymeric material, such as at least a partially crosslinked polymeric material (eg, gel or hydrogel). In some embodiments, the at least one polymeric material easily incorporates or mixes fluids or liquids. A gel or hydrogel is a system that includes a three-dimensional, physically or chemically bonded polymer network that entraps a fluid or liquid, such as water, into the intermolecular space. As is known in the art, gels or hydrogels can refer to at least partially crosslinked materials that contain a substantial liquid moiety but exhibit little or no flow in steady state. By weight, gels are generally mostly liquid, but can behave like solids due to their crosslinked structure. Due to their ability to adapt to their high water content, porosity, and soft consistency, hydrogels closely simulate natural living tissue. Gels and hydrogels can be chemically stable, or they can decompose and eventually disintegrate and dissolve. In some embodiments, the at least one lubricant is biocompatible.

For example, useful gels or hydrogels include polyethylene glycol, polyvinylpyrrolidone, polytetrafluoroethylene, polyvinyl alcohol, polyacrylamide, polymethacrylic acid, and / or hydrogels containing polyacrylic acid (PAA), and / or disulfide crosslinks ( It can contain one or more of poly (oligo (ethylene oxide) monomethyl ether methacrylate) (POEMA). As a result of uptake or contamination of fluids (such as water), some hydrophilic materials Can be gelled, smooth, and / or smooth.

Thus, in the presence of fluid (moisture and / or urine, etc.), the hydrophilic material of the lubricant provides increased lubricity between the stent or catheter device 7010 and the adjacent portion of the patient's urinary tract. can do.

Combinations or mixtures of hydrophilic, non-hydrophilic, and / or polymer-lubricating materials can be used in the same coating / impregnation or different coatings / impregnations, or layers thereof, as desired. In some embodiments, the concentration of at least one coating and / or at least one lubricant in the impregnated 7022 prior to drying or curing is from about 0.1 to about 0.1 based on the total weight of the coating / impregnated material composition. It can range from 99.9 weight percent or 100 weight percent, or about 20-100 weight percent, or about 50 to about 100 weight percent. In some embodiments, the concentration of at least one coating and / or at least one lubricant in the impregnated 7022 after drying or curing is from about 0.1 to the total weight of the dried or cured coating / impregnation. It can range from about 99.9 weight percent or 100 weight percent, or about 20-100 weight percent, or about 50 to about 100 weight percent.

In some embodiments, the at least one coating and / or impregnated 7022 can include, for example, at least one antibacterial material to inhibit tissue growth and / or prevent infection. For example, any one of the at least one coating and / or the impregnated 7022, such as any of the outermost layer 7024 and / or the sublayer 7026, may contain at least one antibacterial material itself, or at least one antibacterial material. It can include a polymer matrix formed from a suitable biocompatible material impregnated with one or more materials including, for example, an antibacterial material. Alternatively, or in addition, the accessory layer 7026 can include a liposome coating or similar material and can be configured to deliver bacteriophage or drug therapy. The antibacterial material may refer to, for example, at least one of a bactericidal material, an antiviral material, an antibacterial material, an antifungal material, and / or an antibiotic material such as an antibiotic drug or a therapeutic agent. Examples of suitable antibacterial, antifungal, and / or fungicides and materials can include chlorhexidine, silver ions, nitrogen oxides, bacteriophage, sirolimus, and / or sulfonamides. Some antibacterial materials, such as sirolimus, can also act as immunosuppressive agents to reduce foreign body responses evoked by indwelling catheters. Examples of suitable antibiotic materials that may be included in at least one coating and / or impregnation 7022 can include amdinocilin, levofloxacin, penicillin, tetracycline, sparfloxacin, and / or vancomycin. The dose or concentration of such antibacterial agent can be selected to avoid or reduce the occurrence of infections as known to those of skill in the art, such as about 1 to about 100 mcg / cm ³ . The antibacterial and / or antibacterial material of the coating is also heparin, phosphorylcholine, silicon dioxide, and to prevent any of protein adsorption, biofilm formation, minerals and / or crystal accumulation, and similar risk factors. / Or a material such as diamond-like carbon can be included. Other suitable antibacterial materials that provide useful functional properties for coatings include other antibacterial peptides, caspofungin, chitosan, parylene, and organosilanes, and other materials that impart mechanical antibacterial properties. Can include.

In some examples, the concentration of at least one coating and / or at least one antibacterial material in the impregnated 7022 prior to drying or curing is from about 0.1 based on the total weight of the coating / impregnated material composition. It can range from about 99.9 weight percent or 100 weight percent, or about 20-100 weight percent, or about 50 to about 100 weight percent. In some examples, the concentration of at least one coating and / or at least one antibacterial material in the impregnated 7022 after drying or curing is about 0.1 based on the total weight of the dried or cured coating / impregnation. It can range from about 99.9 weight percent or 100 weight percent, or about 20-100 weight percent, or about 50 to about 100 weight percent.

In some embodiments, at least one coating and / or impregnated 7022 containing an antibacterial material should provide suitable protection for the device 7010 coated over the life of the device 7010, but antibacterial. The duration of the property can be shorter. Thus, at least one coating and / or impregnation 7022 can be from about 1 day to about 1 year, or from about 10 days to about 180 days, or from about 30 days to about 90 days, the useful life of the coated device 7010. It should be thick enough and contain sufficient antibacterial material to continue exhibiting antibacterial properties throughout.

In some embodiments, as an alternative or in addition, the at least one coating and / or impregnation 7022 may include at least one pH buffering material to buffer the pH of a fluid in the urinary tract such as urine. can. Such cushioning material may reduce or eliminate the jacket, which may adhere to the surface of the coated device 7010, for example. The pH buffering material is often thought to reduce the coat by blocking or preventing the formation of urinary crystals that adhere to indwelling structures located in the urinary tract. For example, in the presence of an organism capable of producing urease enzymes, local increases in ammonium concentration and pH can result in the formation of crystals of at least one of calcium phosphate, magnesium phosphate, or magnesium ammonium phosphate. On the other hand, urate and oxalate crystals are more commonly found with decreasing pH levels. The pH of urine can range from about 4.5 to about 8.0, typically about 6.0.

When the pH of the fluid in the urinary tract rises above a predetermined value, for example 6.0 or 7.0, the at least one coating and / or impregnation 7022 is part of at least one cushioning material or Everything can be released into the fluid. Alternatively, or in addition, when the pH of the fluid in the urinary tract drops below a predetermined value, such as 5.5 or 6.0, the at least one coating and / or impregnation 7022 is at least one. Part or all of the buffer material can be released into the fluid. As an alternative or in addition, at least one coating and / or impregnation 7022 is at least one when the concentration of at least one of calcium, magnesium, phosphorus, oxalate, or uric acid reaches a given value. Some or all of the cushioning material can be released into the fluid. For example, in patients with elevated levels of calcium, magnesium, phosphorus, oxalate, or uric acid in their fluid or urine, at least one coating and / or impregnation 7022 is at least one buffer. Examples of suitable predetermined values of the specimen capable of releasing some or all of the material into the fluid are at least about 15 mg / deciliter (dl) for calcium, at least about 9 mg / dl for magnesium, and phosphorus. Is at least about 60 mg / dl, at least about 1.5 mg / dl for oxalate, and at least about 36 mg / dl for uric acid. Calcium is commonly referred to specifically as a ratio to urinary creatinine, i.e. the normal value would be urinary calcium: urinary creatinine <0.14. The level of these specimens in fluid or urine can be determined using one or more of colorimetric, spectroscopic, or microscopic methods of fluid or urine. "Normal" values and reference ranges are provided in "mg / 24 hours" units, as excretion is often highly facilitated by dietary intake and therefore expected to be variable over time. Will be done. The excretion of these specimens can also be significantly affected by the use of certain agents, such as diuretics. The device may essentially "sense" and react to sample levels by releasing one or more buffers as a result of binding of the sample to at least a portion or component of the coating layer. A predetermined threshold is specifically for determining the binding affinity of the coating layer such that different levels of binding will induce the release of one or more buffers in varying amounts, if desired. It can be set for a target sample.

Examples of suitable pH buffering materials can include, for example, acid salts impregnated in the soluble polymer material layer. As will be appreciated by those skilled in the art, an acidic solution is produced as the acid salt dissolves in the presence of body fluids or water. Desirably, the acidic solution produced is less acidic so as to prevent the formation of the coat but not damage the body tissue. Examples of suitable acid salts that can be used as a suitable pH buffer layer can include weakly acidic salts such as sodium citrate, sodium acetate, and / or sodium bicarbonate. In some examples, the pH buffer material is dispersed in a hydrogel, colloid, and / or copolymer matrix such as methacrylic acid and methyl methacrylate copolymers and has high affinity calcium or phosphorus such as ethylene glycol tetraacetic acid (EGTA). It can be dispersed or stratified with a acid acid binder.

In some examples, the concentration of at least one coating and / or at least one pH buffering material in the impregnated 7022 prior to drying or curing is from about 0.1 to about 0.1 based on the total weight of the coating / impregnated material composition. It can range from about 99.9 weight percent or 100 weight percent, or about 20-100 weight percent, or about 50 to about 100 weight percent. In some examples, the concentration of at least one coating and / or at least one pH buffer material in the impregnated 7022 after drying or curing is about 0.1 based on the total weight of the dried or cured coating / impregnation. It can range from about 99.9 weight percent or 100 weight percent, or about 20-100 weight percent, or about 50 to about 100 weight percent.

In some embodiments, the at least one coating and / or impregnated 7022 comprises an outermost layer 7024 and a single or multiple sublayers 7026 (eg, either an antibacterial sublayer or a pH buffering sublayer). Can be provided. In another embodiment, the sublayer 7026 of at least one coating and / or impregnation 7022 is applied to the outer surface 7028 of the device 7010, including, for example, a pH buffering material for reducing the coat of urinary crystals. A first sublayer 7030 and a second sublayer 7032 covering at least a portion of the first sublayer 7030 can be provided, for example. The second sublayer 7032 can contain, for example, an antibacterial material. Alternatively, the first sublayer 7030 can contain an antibacterial material and the second sublayer 7032 can contain a pH buffering material.

In some embodiments, as an alternative or in addition, the at least one coating and / or impregnation 7022 can include at least one anti-inflammatory material. Following insertion into the body, proteins and other biomolecules within the body, such as in plasma and biological fluids, are absorbed onto the surface of the biomaterial of the device or implant. Non-specific biomolecular and protein adsorption known as "biofouling" and subsequent leukocyte attachment can result. Subsequent inflammatory reactions such as protein adsorption, leukocyte recruitment / activation, inflammatory mediator secretion, and biomaterial-mediated inflammation, which is a complex reaction of some or all fibrous encapsulations of devices or implants, result. obtain. Reducing the inflammatory response, for example by reducing the ability of protein bindings and immune responses to propagate, is considered a potential for urinary tract tissue through contact with the device in the absence or presence of negative pressure. Can prevent or reduce injury.

Non-limiting examples of suitable anti-inflammatory materials include anti-inflammatory agents and non-adherent surface treated materials. Examples of suitable anti-inflammatory agents include at least one of dexamethasone (DEX), heparin, or alpha-melanocyte stimulating hormone (α-MSH). Examples of suitable non-adhesive surface treatment materials include polyethylene glycol-containing polymers, poly (2-hydroxyethylmethacrylate), poly (N-isopropylacrylamide), poly (acrylamide), phosphorylcholine polymers, mannitol, oligomaltose, or. Includes at least one of the taurine groups.

In some examples, the concentration of at least one coating and / or at least one anti-inflammatory material in the impregnated 7022 prior to drying or curing is about 0.1 based on the total weight of the coating / impregnated material composition. It can range from about 99.9 weight percent or 100 weight percent, or about 20-100 weight percent, or about 50 to about 100 weight percent. In some examples, the concentration of at least one coating and / or at least one anti-inflammatory material in the impregnated 7022 after drying or curing is about 0. It can range from 1 to about 99.9 weight percent or 100 weight percent, or from about 20 to 100 weight percent, or from about 50 to about 100 weight percent.

In some embodiments, the at least one coating and / or impregnated 7022 can comprise an outermost layer 7024 and a single or multiple sublayers 7026 comprising at least one anti-inflammatory material. In some embodiments, the outermost layer 7024 can contain at least one pH buffering material and one or more sublayers 7026 can contain at least one anti-inflammatory material.

In some embodiments, the overall thickness of at least one coating and / or impregnation 7022, or depth of impregnation into the device material, is about 0. 001 micrometers (about 1 nanometer) to about 10.0 millimeters, or about 0.001 micrometers to about 5 mm, or about 0.001 mm to about 5.0 mm, or about 0.01 mm to about 1.0 mm, or It can range from about 0.001 micrometer to about 0.2 mm. In some embodiments, each coating / impregnated layer within the plurality of coating / impregnated layers is about 0.001 micrometer to about 10.0 mm, or about 0, after application of the coating / impregnated layer and drying or curing. It can have a thickness ranging from 0.01 micrometer to about 5.0 mm, or from about 0.001 micrometer to about 500 micrometer.

In some embodiments, the overall thickness of at least one hydration or expansion coating and / or impregnation 7022, or the depth of impregnation into the device material, is from about 0.1 micrometer to about 25.0 millimeters. , Or can range from about 0.1 micrometer to about 500 micrometers, or about 20 micrometers ± 20%.

In some embodiments, the density of the coating / impregnated material composition can range from about 0.1 to about 200 mg / microliter, or about 1 mg / microliter prior to drying or curing. The coating / impregnating material to be applied to the device 7010 prior to drying or curing is further a silica oil such as water, alcohol, polydimethylsiloxane, and / or a hydrogel containing, for example, polyacrylic acid (PAA) and / or It can include at least one carrier or auxiliary agent such as a polymer matrix material such as disulfide crosslinks (poly (oligo (ethylene oxide) monomethyl ether methacrylate) (POEMA).

In some embodiments, the concentration of at least one of the lubricant, antibacterial, pH buffer, or anti-inflammatory material in the coating / impregnating material composition prior to drying or curing is used for the individual layers. It can range from about 0.1 to about 99.9 weight percent or 100 weight percent based on the total weight of the coated / impregnated material composition to be applied. In some embodiments, the coating / impregnated material composition is in an amount ranging from about 0.001 mg / cm ² to about 5 mg / cm ² or about 2 mg / cm ² ± 50% per layer, and the device prior to drying or curing. It can be applied to 7010. In some embodiments, for a coating / impregnating material composition comprising at least one antibacterial agent, the coating / impregnation is about 0.001 mg / cm ² to about 5 mg / cm ² or about 2 mg / cm ² ± 50 per layer. %, Or an amount ranging from about 0.005 mg / cm ² to about 0.025 mg / cm ² , and can be applied to the device 7010 prior to drying or curing.

In some embodiments, the outermost coating / impregnated layer 7024 contains at least one lubricant. In some embodiments, at least one lubricant (such as a hydrophilic material, gel, or hydrogel) is to remain, or at least one coating and / or impregnation 7022 of the catheter device 7010 under a lubricant coating. Alternatively, they were exposed to a fluid (such as water and / or urine) that would occur when the catheter device 7010 was deployed in the patient's urinary tract 1 to expose or uncover other material on the outer surface 7028. Sometimes at least partially or completely dissipated. For example, as the lubricant dissipates, one or more sublayers or sublayers located below the outermost layer 7024 may be exposed. The lubricant of the outermost layer 7024 can be configured to dissipate into the surrounding fluid or tissue within a desired period following embedding. Some or all of the outermost layer 7024 may be intended to facilitate insertion and positioning of the coated device 7010 primarily within a fairly short period of time following insertion into the urinary tract 1. Can dissipate. For example, the outermost layer 7024 is completely, substantially, or partially within 6 hours to 10 days, or 12 hours to 5 days, or 1 to 3 days following insertion and / or placement in the urinary tract. It may be configured to dissipate. As used herein, the material, such as some or all of the outermost layer 7024, is at least about 90%, or at least about 95%, or about 95%, or about 98% of the outermost layer 7024 catheter. It is released from the coating under the surface or outermost layer of 7010 and is substantially dissipated when absorbed into the surrounding fluid and / or tissues 1003, 1004 and / or discharged from the patient's body. In some embodiments, the outermost layer 7024, which dissipates within 1-10 days, is 0.01 micrometer to 5.0 when prior to hydration or activation, or when hydrated or activated. It can have a total thickness of millimeters, or 0.001 mm to 2.5 mm, or 0.01 mm to 1.0 mm. In some embodiments, the thickness of the outermost layer 7024 dissolves into the urinary tract before exposing at least one coating and / or impregnation 7022 of the catheter device 7010 and / or an accessory layer 7026 of the outer surface 7028. At some point, the outermost layer 7024 may largely depend on the length of time it should remain in place.

Depending on the dissipation of the outermost layer 7024, the material of one or more sublayers 7026 located below the outermost layer 7024 may remain in place and provide a particular property or function over a long period of time, or peripheral. It may be configured to be released into the fluid and / or tissue and provide, for example, the desired therapeutic or beneficial effect for the surrounding fluid and / or tissue. For example, the material of one or more sublayers 7026 is sustained release into the surrounding tissue over a period of about 1 day to about 1 year, or about 30 days to about 180 days, or about 45 days to about 90 days. Can be configured for. In some embodiments, the rate of dissipation for the sub-layer 7026 depends on the thickness of the outermost layer 7024. For example, the sublayer 7026 can have a total thickness ranging from about 0.01 micrometer to 5.0 mm, or about 0.01 mm to 4.0 mm, or about 0.1 mm to 3.0 mm. In some embodiments, the thickness of the accessory layer 7026 remains or dissolves and releases the material to improve the function of the catheter device 7010 over the entire useful life or the time the device 7010 is in the urinary tract. It can be selected as it can.

In some examples, part or all of the period during which the coated device 7010 is in the urinary tract, as in other embodiments the outermost layer 7024 remains attached to the coated device 7010. Throughout, it can be configured to maintain its beneficial properties. For example, the outermost layer 7024 may remain in place for a period of up to 10, 45, 90 days, or at least one year when in the patient's urinary tract 1. In order to maintain beneficial or hydrophilic properties for at least one year, the outermost layer 7024 can be as thick as, or thinner than 0.01 mm, or possibly thicker than 5.0 mm, up to a maximum. It can be 10.0 mm thick. Alternatively, or in addition, the outermost layer 7024 can be formed from a material that does not dissolve or decompose, or slowly decomposes only when in urinary tract 1. For example, slippery or low-friction non-hydrophilic materials such as polytetrafluoroethylene (PTFE) (eg, Teflon®) may remain in place without dissolution over a long period of time.

When configured to maintain properties such as hydrophilicity over a long duration, the outermost layer 7024 is time dependent so that the bulk material of the sublayer 7026 can pass through the outermost layer 7024 to the surrounding fluid and / or tissue. It can be configured for sexual permeability or release. For example, the outermost layer 7024 can be provided with a structure and / or void space to allow moisture or fluid to penetrate through the outermost layer 7024 to one or more sublayers 7026. To obtain such permeability, the outermost layer 7024 can contain a composite material and bulk hydrophilicity is maintained, while at least one contributing material of the outermost layer 7024 has selective diffusibility. , Soluble and / or porous (eg, microporous, mesoporous, or macroporous) and the like. According to the International Union of Pure and Applied Chemistry (IUPAC) nomenclature, micropores, mesopores, and large pores are less than 2.0 nanometers and 2.0-, respectively. Materials exhibiting pores with diameters greater than 50 nanometers and 50 nanometers will be described. Processes that can be used to form porous materials can include, for example, phase separation, gas formation, and soft and hard mold techniques, as well as other selective and additive manufacturing methods.

Alternatively, or in addition, as shown graphically in FIG. 56, the outermost layer 7024 extends through the outermost layer 7024 to one or more sub-layers 7026, at least one opening, hole, space, and. / Or microchannel 7052 can be provided. At least one opening, hole, space, and / or microchannel 7052 can be endogenous, spontaneous, or produced (artificial) within the material of the outermost layer 7024. For example, the outermost layer 7024 may necessarily be porous. In some embodiments, at least one opening, hole, space, and / or microchannel is by any suitable process comprising, for example, pressing a pin or puncture needle through a hardened outermost layer 7024. Can be formed. In other embodiments, at least one opening, hole, space, and / or microchannel 7052 can be formed by etching or melting a portion of the outermost layer 7024. At least one opening, hole, space, and / or microchannel 7052 allows fluid such as moisture to pass through the outermost layer 7024 to the sublayer 7026, and the dissolved material from the sublayer 7026 is the outermost layer 7024. It can be configured to pass through at least one opening, hole, space, and / or microchannel 7052 to the surrounding fluid and / or tissue. In some embodiments, the at least one opening, hole, space, and / or microchannel 7052 initially has one or more sublayers 7026 fluid as soon as the device 7010 is positioned in the urinary tract. It extends throughout the outermost layer 7024 so that it can penetrate into. In other embodiments, the at least one opening, hole, space, and / or microchannel 7052 may partially extend through the outermost layer 7024. In that case, fluid such as water or urine collects in at least one opening, hole, space, and / or microchannel 7052 and at least one during the initial period following insertion into the urinary tract. It can dissolve openings, holes, spaces, and / or parts of microchannel 7052. Over time, at least one opening, hole, space, and / or microchannel 7052 melts through the rest of the outermost layer 7024 and eventually contacts a portion of one or more sublayers 7026. Expose it. Thus, the release of the functional material of the accessory layer 7026 is delayed until a period of time after the device 7010 is inserted into the urinary tract. At least one opening, hole, space, and / or microchannel 7052 is for fluids such as moisture to pass through and to contact one or more sublayers 7026, and the dissolved material of sublayer 7026 is at least one. It can be of any size and number sufficient to allow passage to peripheral fluids and tissues through one opening, hole, space, and / or microchannel 7052. For example, at least one opening, hole, space, and / or microchannel 7052 is about 0.01 micrometer ² to about 1.0 mm ² , or about 0.1 mm ² to about 0.5 mm ² , or about. It can have a cross-sectional area of 0.2 mm ² to about 0.4 mm ² . At least one opening, hole, space, and / or microchannel 7052 can be formed in or on the outermost layer 7024 in various configurations and arrangements. For example, at least one opening, hole, space, and / or microchannel 7052 is a plurality of openings having any desired configuration, eg, substantially circular, oval, or any shape in cross section. obtain. In another embodiment, the at least one opening, hole, space, and / or microchannel 7052 is in any direction (eg, axially) along the surface of the outermost layer 7024 or within the outermost layer 7024. And / or can be a trough or hole that extends (circumferentially).

As shown in FIGS. 53 and 54, in some embodiments, the sub-layer 7026 is positioned between the outer surface 7028 and the outermost layer 7024 of the device 7010 (extension tube 7012, etc.). The accessory layer 7026 improves the long-term performance of the coated device 7010 by addressing one or more of the problems described above associated with the long-term use of the device 7010, for example, an indwelling catheter. Can be configured as For example, one or more sublayers 7026 to a step of inhibiting tissue inward growth, a step of reducing a foreign body reaction with respect to the tissue surrounding the deployed coated device 7010, to the tissue surrounding the coated device 7010. Improving the long-term performance of the coated device 7010 by one or more of the steps of reducing infection and / or reducing the coat of urinary crystals onto the coated device 7010. Can be done.

In some embodiments, the fluid and / or tissue 1003 surrounding the coated device 7010, wherein the at least one coating and / or impregnation 7022 may be brought into contact with the device 7010 by natural force or applied negative pressure. Intended to come into contact with part of 1004. Thus, the at least one coating and / or impregnation 7022 is the outer peripheral edge 72, 1002, or the outward facing side, or at least one of the protective surfaces 1001, 7038, such as the retaining portion 7020 of the device 7010. It may need to be applied only to parts or all. In some cases, the inner peripheral edge, inward facing side, or protected surface area of the retention portion 7020, including at least one protected drain hole, port, or perforation 7036, as described above. 1000, 7034 can be substantially free or free of at least one coating and / or impregnation 7022. Alternatively, as described in connection with FIG. 57, the protected surfaces 1000, 7034 and the protected surfaces 1001, 7038 of the device 7010 are both, for example, one or more of the aforementioned benefits of the coating. And / or may be coated with at least one coating and / or impregnation 7022 to facilitate manufacturability (eg, deposition of coating on device 7010).

The at least one coating and / or impregnation 7022 described herein is to be used in combination with any or all of the devices 7010 such as stents, ureteral catheters, and / or bladder catheters described herein. Can be adapted. For example, the kidney and device 7010 such that at least one coating and / or impregnation 7022, when deployed at the desired location within the kidney and / or renal pelvis, allows at least a portion of the fluid to flow through the expandable retention portion 7020. With an expandable retention portion 7020 that defines a three-dimensional shape 7040 that is sized and positioned to maintain fluid flow patency between the proximal portion 7014 and / or the proximal end 7016 of the pelvis. It can be applied to a device 7010 comprising a position portion 7018. In that case, the at least one coating and / or impregnation 7022 may be applied to a portion of the retention portion 7020 that contacts the surface of the three-dimensional shape 7040. Further, as in the embodiments described above, to match the size and shape of the renal pelvis, it is defined by an expanded expandable retention portion 7020 in a plane across the central axis A of the expandable retention portion 7020. The area of the two-dimensional slice 7042 of the three-dimensional shape 7040 can be increased towards the distal end 7044 of the expandable retention portion 7020.

In some embodiments, the retention portion 7020 comprises a coiled retention portion that extends radially from the renal pelvis to the kidney. The coiled retaining portion 7020 can include at least a first coil 7046 (shown in FIG. 52B) having a first diameter D1 and at least a second coil 7048 having a second diameter D2. .. The first diameter D1 can be less than the second diameter D2 to accommodate the size and shape of the renal pelvis. In some embodiments, at least one coating and / or impregnated 7022 is the outer or protective surface 1001, 7038 of the coils 7046, 7048, as only such outer or protective surfaces 1001, 7038 are contacted by body tissue. Should only apply to. The protected surfaces 1000, 7034 of the coils 7046, 7048 may not be coated with at least one coating and / or impregnation 7022.

In some embodiments, at least some or all of the protected surfaces 1001, 7038 and the protected surfaces 1000, 7034 of the device 7010, such as coils 7046, 7048, are coated with at least one coating and / or impregnation 7022. Can be done. For example, applying at least one coating and / or impregnation 7022 to all surfaces of the device 7010 or extension tube 7012 may be easier for manufacture or production. In some embodiments, the device 7010, eg, the entire extension tube 7012, may have a substantially linear (eg, non-coiled) configuration during insertion of the extension tube 7012 or device 7010 through the patient's urinary tract. , Hydrophilic or may be coated with the outermost layer 7024. The sublayers 7030, 7032, which may help improve the long-term performance of the device 7010, are a portion of the device 7010 or extension tube 7012 that is likely to be contacted by body fluids or tissues (eg, the outward surface of the tube 7012). It needs to be applied only to the part that was used.
Multi-layer coating / impregnation for continuous functionality

In another embodiment, as shown in FIG. 57, the coated device 7110 comprises one or more coatings and / or impregnations 7122 having multiple or different functionality. The coating and / or impregnation 7122 can be applied to at least some or all of the device 7010. As in previous embodiments, the coating and / or impregnation 7122 can include one or more outermost layers 7124 and one or more innermost layers 7126. The coating and / or impregnation 7122 can further comprise a plurality of sublayers 7128, 7130, 7132 located between the one or more outermost layers 7124 and the one or more innermost layers 7126. Multiple sublayers 7128, 7130, 7132 can be formed from different materials, respectively, to address different problems with indwelling catheters and / or provide different functional improvements for device 7110. .. The one or more outermost layers 7124 and the plurality of sublayers 7128, 7130, 7132 are coated and / or impregnated with a first property or functionality over a predetermined period of time, a second property over a predetermined second period. And may be configured to dissipate continuously to provide a third property over a predetermined third period. For example, one or more coatings and / or impregnations 7122 may dissipate the outermost layer 7124 and sublayers 7128, 7130, 7132 over time, but but with an intermittent period of drug delivery and / or antibacterial. Alternatively, it may be configured to provide a periodic and / or intermittent effect, including a period of antibacterial effect. In some cases, drug delivery is prior, such as limiting drug delivery to 12-hour, 24-hour, or 48-hour release following insertion of the coated device 7110 into the urinary tract. It can be controlled to occur at a specified time. Similarly, another 12-hour, 24-hour, or 48-hour release of the drug may be provided prior to the removal of the coated device 7110.

The outermost layer 7124 may be substantially similar in thickness and material properties to the outermost layer described above. For example, the outermost layer 7124 can provide a lubricious outer surface that is configured to facilitate insertion and installation of the device 7110 in the urinary tract in the absence of a lubricating coating. The outermost layer 7124 can be configured to remain or can be dissipated immediately after implantation within the body, such as within 1-10 days of implantation.

The plurality of sublayers 7128, 7130, 7132 can be selected such that the sublayers remain for a predetermined period of time and dissipate for the duration or intended duration of the catheter device 7110 in the urinary tract. For example, with respect to a catheter designed to be present in the urinary tract over a period of 10-20 days, each of the 5 sublayers may be configured to dissipate or dissolve in about 2-4 days. As discussed above, in another embodiment, the layer containing the therapeutic agent may dissipate within 12 hours, 24 hours, or 48 hours of insertion. Sublayers containing antibacterial materials and / or other materials such as pH buffering materials dissipate over longer periods of time, such as 1 to 10 days, or 2 to 8 days, or 3 to 5 days. You may.

In some embodiments, the plurality of sublayers 7128, 7130, 7132 comprises a first sublayer 7128 located below the outermost layer 7124. The first sublayer 7128 can be configured to begin to dissipate into the surrounding tissue when contacted by moisture, as it occurs once a portion of the outermost layer 7124 dissipates. As in the previous embodiment, the material of the first sublayer 7128 can be configured to address problems with indwelling catheters and / or improve the functional properties of the coating 7122. For example, the first sublayer 7128 can comprise an antibacterial layer that provides protection from the invasion of microorganisms into or on the coating 7122 for a predetermined period of time, such as several days following implantation.

Over the hours and / or days following insertion, the first sublayer 7128 dissipates and exposes the second sublayer 7130 to fluid or moisture. The second sublayer 7130 can include one or more coating and / or impregnating materials to provide another property for improving the functionality of the device 7110. For example, the second sublayer 7130 can include a dose of a therapeutic agent, such as a dose of antibiotic. The second sublayer 7130 is to deliver a dose of the therapeutic agent over a short period (eg, hours or days), or for a slightly longer period (eg, 1-10 days, or 2-8 days). , Or for sustained release of the therapeutic agent over 3-5 days), can be configured with either. Once the therapeutic agent is released and the second sublayer 7130 dissipates into the surrounding fluid or tissue, the third sublayer 7132 can be exposed to urinary tract water or fluid. The third sublayer 7132 may contain materials with additional or different functional properties. For example, the third sublayer 7132 can be a pH buffer layer for reducing or eliminating the presence of a jacket on the device 7110. In other examples, the third sublayer 7132 may be another antibacterial and / or antibacterial layer. The third sublayer 7132 can be configured to stay in place for hours or days, as in the case of previous sublayers or layers.

The device 7110 further comprises one or more additional sublayers 7026 containing materials with different properties to address the problem of indwelling catheters and / or to improve the function of the coating 7122 and the coated device 7110. Can be prepared. For example, the coating 7122 may comprise several therapeutic layers, including a dose of an antibiotic formulation positioned between the accessory layers 7026 containing an antibacterial material. Therefore, the coating 7122 provides an intermittent antibiotic dose that is separated by the period of non-delivery of the antibiotic, thereby reducing the risk that the antibiotic concentration will increase above suitable levels. Can be done.

In some embodiments, the coating 7122 also comprises an innermost layer 7126, located between the outer surface 7124 of the device 7110 or extension tube 7112 and the innermost sublayer 7128. The innermost layer 7126 may be similar in size and material composition to the outermost layer 7124 described herein. For example, the innermost layer 7126 may contain any of the coating materials discussed above, such as hydrophilic materials, which become lubricated when exposed to moisture. In some embodiments, the innermost layer 7126 can be exposed immediately prior to removal of the device 7110. Once exposed to fluid or moisture, the innermost layer 7126 can be configured to be slippery and lubricious, which aids in the removal of the device 7110 through the urinary tract. For example, when the innermost layer 7126 is in a lubricated state, the extension tube 7112 of the device 7110 can slide more easily through the body tissue to facilitate removal of the device 7110.
How to make a coated and / or coated catheter

A method of making a coated and / or impregnated device 7010, such as a coated and / or impregnated catheter and / or a stent device, is shown in FIG. 55. The method comprises steps 7210-7222, many of which can be performed in any order. For example, at least one coating and / or impregnation 7022 may be applied directly to the device 7010 prior to forming the other portion of the device 7010. Alternatively, as shown in FIG. 55, at least one coating and / or impregnation 7022 can be applied to the device 7010 as a final step prior to packaging the device 7010. Also, some of the steps shown in FIG. 55 are optional and do not need to be performed to make the device 7010 and / or at least one coating and / or impregnation 7022. For ease of discussion, the method is discussed below with reference to preparing a device, comprising a coil from an extension tube, but other disclosed herein, such as a funnel or sponge. Any of the device embodiments can be prepared in a similar fashion.

As shown in FIG. 55, in some embodiments, the method first has at least one opening, hole, space over a portion of the device 7210, such as an extension tube, as shown in 7210. And / or include the step of forming the microchannel 7036. For example, at least one opening, hole, space, and / or microchannel 7036 may be formed by puncturing a portion of an extension tube or device 7210 using a needle, drill, or similar tool. can. The openings, holes, spaces, and / or microchannels can be equidistant along the length of the device 7210 or extension tube. Alternatively, at least one opening, hole, space, and / or microchannel near the distal end of the device 7210 or extension tube to improve the distribution of negative pressure applied through the device 7210 or tube. They may be closer together and separated. At least one opening, hole, space, and / or microchannel can be the same or different sizes as described herein. Alternatively, at least one opening, hole, space, and / or microchannel near the distal end of the tube can be larger to improve the negative pressure distribution, as described herein. ..

In some embodiments, the method can further include forming a retention portion 7020 on the distal portion 7018 of the extension tube 7012, as shown in 7212. As in the embodiments described above, the retention portion 7020 can be configured to transition between a contracted state and an expanded or expanded state. In the unfolded state, the retaining portion 7020 can include an inwardly facing side or a protected surface 7034 and an outwardly facing side or a protected surface 1001, 7038. Desirably, at least one opening, hole, space, and / or microchannel 7036 is positioned on the inward facing side or protected surface 7034 of the retention portion 7020 when unfolded. The outward facing sides or protective surfaces 1001, 7038 can be deployed with virtually no drain ports, openings, holes, and perforations 7036.

The retention portion 7020 can be formed using a variety of techniques. With respect to the coiled retainer portion, the extension tube 7012 may be wound around a template or mandrel over a long period of time to provide the desired curvature for the coil. For other types of expandable retainers such as expandable cages or frames, the steps to form the retainer include bending or machining a member such as a metal splinter into the desired shape and extending the cage or frame. Can include steps to attach to the distal portion of. Similarly, a balloon-shaped retention portion can also be attached to the distal portion of the extension tube.

At least one coating and / or impregnation 7022 can be applied to the device 7010 at any time during device formation, as shown in steps 7214-7220. In 7214, optionally, the method of forming at least one coating and / or impregnation 7022 first lubricates the innermost layer 7126 of the device 7010, such as the surface 7028 of the extension tube 7012 of the catheter and / or stent device. Includes steps to apply. For example, the innermost layer 7126 may be applied to a device 7010 or a distal portion of an extension tube, such as a device 7010 configured to be deployed in the urinary tract or part of a tube. In 7216, in some embodiments, the method further comprises applying one or more sublayers 7026. The sub-layer 7026, if present, covers at least a portion of the innermost layer 7126. In the absence of the innermost layer 7126, the sub-layer 7026 can be applied directly to a portion of the device 7010, such as directly to the outer surface 7028 of the extension tube. As described above, the accessory layer 7026 can be configured to address the problems associated with indwelling catheters and / or improve the long-term performance of the device.

At least one coating and / or impregnation 7022 can be applied using conventional coating techniques and processes. For example, at least one coating and / or impregnation 7022 may be applied to the device 7010 by spraying the coating / impregnation material on a portion of the device 7010 layer by layer, followed by drying of the material. Allows for hardening or hardening. In another embodiment, the layer-by-layer coating / impregnating material can be dropped or coated onto the surface of the device 7010. In another embodiment, a portion of the device 7010 can be continuously immersed or immersed in a bath of coating / impregnating material layer by layer for multiple coatings. In other examples, the coating / impregnating material is dispersion polymerization, suspension polymerization, bulk polymerization, atomic transfer radical polymerization (ATRP), chemical vapor deposition polymerization, radical emulsion polymerization, polycondensation reaction, supercritical fluid method, self-aggregated colloid. It can be applied by any combination of the crystal template method, the sacrificial polymer template method, the high internal phase emulsion template method, and the methods discussed herein.

As discussed above, the at least one coating and / or impregnation 7022 is preferably formed from one or more materials that improve the long-term performance of the coating and / or device 7010. For example, at least one coating and / or impregnation 7022 can block tissue inward growth, reduce foreign body reactions to the tissue surrounding the deployed device, and infect the tissue surrounding the deployed device. The reduction step and / or one or more of the steps of reducing the urinary crystal coat on the device may be configured to improve the long-term performance of the indwelling device 7010.

In some examples, as shown in 7218, one or more additional sublayers 7026 can be applied to the surface of the initially applied sublayer. For example, as described above, the first sublayer 7030 can be a pH buffer sublayer formed from a pH buffer material. Subsequent sublayers can be antibacterial sublayers such as antibacterial and / or sublayers containing antibiotic material.

Following the formation of the sub-layer 7026, at 7220, one or more outermost layers 7024 are applied covering a portion of the sub-layer 7026. As described above, in some embodiments, the outermost layer 7024 can include a hydrophilic lubricating material, such as a hydrophilic material, which gels in the presence of moisture and increases lubricity. .. Other low friction and / or smooth materials can also be used as described herein.

Once at least one coating and / or impregnation 7022 and discharge and retention portion 7020 are formed on the device 7010, the device 7010 may be substantially ready for delivery to the user. To provide the device 7010 to the user, at 7222, the device can be sterilized and placed in a suitable package. The packaged device 7010, such as a catheter or stent, can then be shipped to the user, along with instructions for use and any other required information.
System for inducing negative pressure

In some embodiments, a system is provided to induce negative pressure within a portion of the patient's ureter or to remove fluid from the patient's ureter, providing at least one of the patient's kidneys and the bladder. A bladder catheter with a ureteral stent or ureteral catheter to maintain patency of fluid flow between and a bladder catheter and a distal drainage lumen for draining fluid from the patient's bladder. A pump that communicates fluidly with the end, actuating the pump, applying negative pressure to the proximal end of the catheter, inducing negative pressure into part of the patient's ureter and removing fluid from the patient's ureter. Equipped with a controller, equipped with a pump and configured to.

In some embodiments, a system for inducing negative pressure within a portion of the patient's ureter is provided, the system being as close as possible to (a) the distal portion for insertion into the patient's kidney. A ureteral catheter with a position portion, (b) a distal portion for insertion into the patient's bladder, and a proximal portion for the application of negative pressure, extending outside the patient's body. A bladder catheter with a proximal portion, and (c) outside the patient's body for the application of negative pressure through both the bladder catheter and the ureteral catheter, and thus fluid from the kidney, urine. The ureteral catheter is equipped with a pump that allows both the ureteral catheter and the bladder catheter to be pulled out of the patient's body.

In some embodiments, a system for inducing negative pressure within a portion of the patient's urinary tract is provided, the system being (a) at least one ureteral catheter in the patient's kidney. At least one ureteral catheter comprising a distal portion for insertion and a proximal portion, (b) a distal portion for insertion into the patient's bladder, and receiving negative pressure from a negative pressure source. A bladder catheter comprising a proximal portion for, wherein at least one of the at least one ureteral catheter or bladder catheter is (a) the proximal portion and (b) the distal portion. It has at least one protected drain, port, or perforation and prevents mucosal tissue from obstructing at least one protected drain, port, or perforation in response to the application of negative pressure through the catheter. Bladder catheter and (c) application of negative pressure through both the bladder and ureteral catheters, with a retaining portion, with a distal portion, configured to establish an outer peripheral edge or protective surface area. A negative pressure source for, thus drawing fluid from the kidney into the ureteral catheter, through both the ureteral and bladder catheters, and then to the outside of the patient's body. To prepare for.

In some embodiments, a system for inducing negative pressure within a portion of the patient's urinary tract, which is (a) at least one ureteral catheter, inserted into the patient's kidney. At least one ureteral catheter comprising a distal portion and a proximal portion for (b) a distal portion for insertion into the patient's bladder and a proximal portion for receiving a pressure differential. With a bladder catheter, the pressure difference causes fluid from the kidney to be drawn into the ureteral catheter, through both the ureteral catheter and the bladder catheter, and then to the outside of the patient's body. Is applied to increase, decrease, and / or maintain fluid flow through it, and at least one of at least one ureteral or bladder catheter is (a) with the proximal portion. (B) A distal portion, comprising at least one protected drain hole, port, or perforation, with at least one protected drain hole in which mucosal tissue is applied in response to application of a pressure differential through the catheter. It comprises a port, or a distal portion, with a retention portion, configured to establish an outer peripheral edge or protective surface area that prevents obstruction of the perforation.

Referring to FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, an exemplary system 1100 for inducing negative pressure into the patient's urinary tract to increase renal perfusion is provided. , Illustrated. The system 1100 comprises one or two ureteral catheters 1212 (or, as an alternative, the ureteral stent shown in FIG. 1A) connected to the fluid pump 2000 to generate negative pressure. More specifically, the patient's urinary tract comprises the patient's right kidney 2 and left kidney 4. Kidneys 2 and 4 are involved in hemofiltration and clearance of waste compounds from the body through urine. The urine or fluid produced by the right kidney 2 and the left kidney 4 enters the patient's bladder 10 through the renal tubules, ie, the right ureter 6 and the left ureter 8 connected to the kidney in the renal pelvis 20, 21. It is discharged. Urine can be conducted through ureters 6 and 8 by peristalsis and gravity of the ureteral wall. The ureters 6 and 8 enter the bladder 10 through the ureteral ostium or opening 16. The bladder 10 is a flexible and substantially hollow structure adapted to collect urine until it is excreted from the body. The bladder 10 can transition from an empty position (indicated by reference line E) to a full position (indicated by reference line F). Normally, when the bladder 10 reaches a substantially full state, fluid or urine is allowed to drain from the bladder 10 to the urethra 12 through the urethral sphincter muscle or opening 18 located in the lower portion of the bladder 10. The contraction of the bladder 10 may respond to the stress and pressure applied on the triangular region 14 of the bladder 10, which is the triangular region extending between the ureteral opening 16 and the urethral opening 18. The triangular region 14 is sensitive to stress and pressure so that the pressure exerted on the triangular region 14 increases as the bladder 10 begins to fill. Beyond the threshold pressure on the triangular region 14, the bladder 10 begins to contract and drains the collected urine through the urethra 12.

As shown in FIGS. 1, 2A, 7A, and 7B, the distal portion of the ureteral catheter is deployed within the renal pelvis 20, 21 in the vicinity of kidneys 2, 4. The proximal portion of one or more of the catheters 1212 enters the bladder, enters the urethra, or exits the body. In some embodiments, the proximal portion 1216 of the ureteral catheter 1212 is in fluid communication with the distal portion or end 136 of the bladder catheters 56, 116. The proximal portion 1216 of the bladder catheters 56, 116 is connected to a negative pressure source such as the fluid pump 2000. The shape and size of the connector can be selected based on the type of pump 2000 used. In some embodiments, the connector can be manufactured with a distinctly different configuration so that it can only be connected to a particular pump type, which creates a negative pressure in the patient's bladder, ureter, or. It is considered safe to induce in the kidney. In another embodiment, as described herein, the connector can be a more general-purpose configuration adapted for mounting on a variety of different types of fluid pumps. System 1100 is just one embodiment of a negative pressure system for inducing negative pressure that can be used in conjunction with the bladder catheters disclosed herein.

Referring here to FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, 7B, 17 and in some embodiments, the systems 50, 100 comprises a bladder catheter 116. The distal ends 120, 121 of the ureteral catheters 112, 114 can be drained directly into the bladder, and fluid is optionally drained through the bladder catheter 116, along the sides of the bladder catheter tube. be able to.
Illustrative bladder catheter

Any of the ureteral catheters disclosed herein can be used as a useful bladder catheter in the method and system. In some embodiments, the bladder catheter 116 anchors, retains, and / or provides passive fixation for the indwelling portion of the urine collection assembly 100, and in some embodiments, the assembly configuration during use. It comprises a retention portion 123 or deployable seal and / or anchor 136 to prevent premature and / or unintended removal of the element. The retention portion 123 or anchor 136 is located adjacent to the lower wall of the patient's bladder 10 (shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, 7B, 17) and the patient. It is configured to prevent the force applied to the exercise and / or indwelling catheters 112, 114, 116 from being transmitted to the ureter. The bladder catheter 116 comprises an interior defining a drainage lumen 140 configured to conduct urine from the bladder 10 to an external urine collection vessel 712 (shown in FIG. 44). In some embodiments, the tube size of the bladder catheter 116 can range from about 8 Fr to about 24 Fr. In some embodiments, the bladder catheter 116 can have an outer diameter ranging from about 2.7 to about 8 mm. In some embodiments, the bladder catheter 116 can have an inner diameter ranging from about 2.16 to about 10 mm. The bladder catheter 116 may be available in different lengths to adapt to anatomical differences for gender and / or patient size. For example, the average female urethral length is only a few inches, so the length of the tube 138 can be quite short. The average urethral length in men is longer and can vary due to the penis. It is also possible for women to use a bladder catheter 116 with a longer length tube 138, provided that excess tubing does not increase the difficulty in operating the catheter 116 and / or preventing contamination of its sterile portion. Considered as sex. In some embodiments, the sterile and indwelling portion of the bladder catheter 116 can range from about 1 inch to 3 inches (female) to about 20 inches (male). The total length of the bladder catheter 116, including sterile and non-sterile parts, can be one to several feet.

In some embodiments as shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, the distal portion 136 of the bladder catheters 56, 116 has one or more drains. Outer perimeter 1002 or perforation 142 that includes a hole, port, or perforation 142 and prevents mucosal tissue from obstructing one or more drainage holes, ports, or perforations 142 in response to the application of negative pressure by the pumps 710, 2000. It comprises a retention portion 123 configured to establish a protective surface area 1001.

In some embodiments, the retention portion 123 comprises a tube 138, in which the tube 138 is configured to be positioned within the bladder 10 to draw urine into the cloaca 140, one or more drain holes. , Ports, or perforations 142. For example, fluid or urine flowing from the ureteral catheters 112, 114 into the patient's bladder 10 is discharged from the bladder 10 through the port 142 and the drain lumen 140. The drain lumen 140 may be pressurized to a negative pressure to assist fluid collection.

In some embodiments as shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, bladder catheters 56, 116 such as the ureteral catheters discussed above. One or more drain holes, ports, or perforations 142, 172 are located on the protected or inner surface surface 1000 of the retention portion 123, and in response to the application of negative pressure, the mucosal tissues 1003, 1004 are bladder catheters. One or more of the protected drain holes, ports, or perforations 172 of the bladder catheters 56, 116, collocated or crushed onto the outer margin 1002 or protected surface area 1001 of the retention portion 173 of 56, 116. It is prevented or blocked so as not to block things.

Specifically referring to FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, 7A, and 7B, the retention portion 123 or deployable seal and / or anchor 136 is the distal end 148 of the bladder catheter 116. Placed in or adjacent to it. The retention portion 123 or the deployable anchor 136 is configured to transition between a contracted state and a deployed state for insertion through the urethra 12 and the urethral opening 18 into the bladder 10. The retention portion 123 or the deployable anchor 136 is configured to be deployed within and adjacent to the lower portion of the bladder 10 and / or to be seated against the urethral opening 18. For example, the retention portion 123 or the deployable anchor 136 is positioned adjacent to the urethral opening 18 to improve the suction of negative pressure applied to the bladder 10, or to partially, substantially, or to the bladder 10. It can be completely sealed to ensure that urine in the bladder 10 is directed through the drainage lumen 140 and prevent leakage to the urethra 12. For the bladder catheter 116, including an extension tube 138 of 8 Fr to 24 Fr, the retention portion 123 or the deployable anchor 136 can have a diameter of about 10 mm to about 100 mm in the deployed state.
Exemplary bladder anchor structure

Any of the ureteral catheters disclosed herein can be used as a useful bladder catheter in the method and system. For example, a bladder catheter can include a mesh as a bladder anchor as shown in FIGS. 1A, 1B, and 7B. In another embodiment, the bladder catheter 116 can be equipped with coils 36, 38, 40, 183, 184, 185, 334, 1210 as bladder anchors as shown in FIGS. 1C-1W and 7A. In another embodiment, the bladder catheter 116 can include a mesh funnel 57 as a bladder anchor as shown in FIG. 7B. In another embodiment, the bladder catheter 116 can include a funnel 150 as a bladder anchor as shown in FIG. Regardless of the embodiment selected, the retaining portion 123 creates an outer peripheral edge 1002 or a protective surface area 1001 to prevent the tissues 1003, 1004 from contracting or crushing the fluid column under negative pressure.

In some embodiments, the retention portion 123 comprises a coiled retention portion similar to the retention portion of the ureteral catheter described in connection with FIGS. 2A and 7A-14. In some embodiments as shown in FIGS. 1C-1E and 1U-1W, the coiled retaining portion 123 has a spiral coil 36, 38, 40, or 438, 436, 432 outer peripheral edges 1002 or outer regions. Protected drain holes, ports, or perforations 172 that contact and support the bladder tissue 1004 and are located within the protected or inner surface area of the spiral coil 36, 38, 40, or 438, 436, 432. Can include a plurality of spiral coils 36, 38, 40, or 438, 436, 432 arranged to prevent obstruction or obstruction.

The coiled retaining portion 123 has at least a first coil 36, 438 having an outer diameter D1 (see FIG. 1E), at least a second coil 38, 436 having an outer diameter D2, and an outer diameter D3. At least a third coil 40, 432 can be provided. The diameter D3 of the most distal or third coil 40,432 can be smaller than the diameter of either the first coil 36, 438 or the second coil 38, 436. Therefore, the diameters of the coils 36, 38, 40, or 438, 436, 432 and / or the step distances or heights between the adjacent coils 36, 38, 40, or 438, 436, 432 are regular or irregular. Can fluctuate in a regular fashion. In some embodiments, the plurality of coils 36, 38, 40, or 438, 436, 432 can form a tapered or inverted pyramid shape where D1> D2> D3. In some embodiments, the coiled retaining portion 123 can comprise a plurality of similarly sized coils, or, for example, a plurality of proximal similarly sized coils and a plurality of coils. Of the other coils can include the most distal coil having a smaller diameter. The diameter of the coils 36, 38, 40, or 438, 436, 432, and the distance or height between adjacent coils is such that the retention portion 123 has a desired period of hours, days, or up to about 6 months. Selected to stay in the bladder over. The coiled retention portion 123 can be large enough to stay within the bladder 10 and not pass into the urethra until the catheter is ready to be removed from the bladder 10. For example, the outer diameter D1 of the most recent or first coil 36, 438 can range from about 2 mm to 80 mm. The outer diameter D2 of the second coil 38, 436 can range from about 2 mm to 60 mm. The most distal or third coil 40,432 can have an outer diameter D3 ranging from about 1 mm to 45 mm. The diameter of the coil tube can range from about 0.33 mm to 9.24 mm (about 1 Fr to about 28 Fr (French catheter scale).

The configuration, size, and location of the holes, ports, or perforations 142, 172 can be any of the configurations, sizes, and locations discussed above with respect to the ureter or other catheter. In some embodiments, the holes, ports, or perforations 142 are present on the outer peripheral edge 1002 or protected surface area 1001, and the protected holes, ports, or perforations 172 are on the protected surface area or inner surface area 1000. exist. In some embodiments, the outer peripheral edge 1002 or the protective surface area 1001 has essentially no or no holes, ports, or perforations 142, and the protected holes, ports, or perforations 172 have a protected surface area or inner surface. It exists on a surface area of 1000.

The retention portion 416 shown in FIG. 1U-1W is a coiled retention portion comprising a plurality of coils wound around a substantially linear or linear portion 430 of the extension tube 418. In some embodiments, the coiled retaining portion 416 comprises a straight portion 430 and a distal coil 432 formed from a bend 434 of about 90 to 180 degrees within the extension tube 418. The retention portion 416 further comprises one or more additional coils, such as a second or central coil 436 and a third or nearest coil 438, wound around a straight portion 430. The extension tube 418 can further be equipped with a distal end 440 after the recent coil 438. The distal end 440 can be closed or opened to receive urine or fluid from the bladder 10.

The area of the two-dimensional slice 34 (shown in FIG. 1E) of the three-dimensional shape 32 defined by the expanded expandable retention portion 123 in the plane across the central axis A of the expandable retention portion 16 is expanded or expanded. Decreasing towards the distal end 22 of the retained retainer 123, the retainer portion 123 can be given a pyramidal or inverted conical shape. In some embodiments, the maximum cross-sectional area of the 3D shape 32 defined by the expanded or expanded retention portion 123 in a plane across the central axis A of the expanded or expanded retention portion 132 is approximately 100 mm ² . It can range from ~ 1,500 mm ² or about 750 mm ² .

Another embodiment of the catheter device 10 is shown in FIG. 1F-1J. The retention portion 123 of the catheter device 10 is configured to be located within the distal portion of the tube 12 in the retracted position and to extend from the distal end of the tube 12 in the deployed position. It comprises a basket-shaped structure of body 210 or outer peripheral edge 1002 or a support cap 212. The bladder upper wall support 210 comprises a support cap 212 configured to support the upper wall or bladder tissue 1004 and a plurality of support members such as legs 214 connected to the proximal surface of the support cap 212. .. The leg 214 can be positioned such that the cap 212 is separated from the open distal end of the drain tube 12. For example, the leg 214 can be configured to maintain a gap, cavity, or space at a distance D1 between the open distal end 30 of the tube 12 and the support cap 212. The distance D1 can range from about 1 mm to about 40 mm or from about 5 mm to about 40 mm. The height D2 of the bladder upper wall support 210 or the retaining portion can range from about 25 mm to about 75 mm, or about 40 mm. The maximum diameter of the support cap 212 can range from about 25 mm to about 60 mm in the unfolded state, preferably from about 35 mm to 45 mm.

In some embodiments, the leg 214 comprises a flexible tip that can be formed from a flexible or shape memory material such as nickel titanium. The number of legs can range from about 3 to about 8. The length of each leg ranges from about 25 mm to about 100 mm, or can be longer if the deployment mechanism is outside the patient's body. The width and / or thickness of each leg, eg, diameter, can range from about 0.003 inches to about 0.035 inches.

In some embodiments, the support cap 212 may be a flexible cover 216 mounted and supported by the legs 214. The flexible cover 216 is from a flexible, soft and / or elastic material, porous material, or a combination thereof, such as silicone or Teflon® to prevent fluid from passing through the cover 216. Can be formed. In some embodiments, the flexible material significantly wears the bladder wall or urethral inner layer when positioned adjacent to the inner mucosal layer, such as silicone or Teflon® material or porous material. Formed from materials that are not irritating, irritating, or damaging. The thickness of the cover 216 can range from about 0.05 mm to about 0.5 mm. In some embodiments, the flexible cover 216 and leg 214 are sufficiently structured so that the cover 216 and leg 214 maintain their morphology when contacted by the superior wall or bladder tissue 1004. Rigidity. Therefore, the legs 214 and the flexible cover 216 prevent the bladder from crushing and occluding the perforation on the retention portion 6 and / or the open distal end 30 of the tube 12. Also, the leg 214 and the flexible cover 216 effectively keep the triangular region and ureteral opening open so that negative pressure can draw urine into the bladder and ureter 12. As discussed herein, if the bladder is allowed to be over-crushed, the tissue valve extends across the ureteral opening, thereby creating a negative pressure on the ureteral catheter, ureteral stent. , And / or prevent transmission to the ureter, thereby preventing urine from being drawn into the bladder.

In some embodiments, the catheter device 10 further comprises a drain tube 218. As shown in FIG. 1G-1J, the drain pipe 218 can include an open distal end 220 located adjacent to or extending from the open distal end 30 of the pipe 12. In some embodiments, the open distal end 220 of the drainage duct 218 is the only opening for drawing urine from the bladder into the interior of the drainage duct 218. In another embodiment, the distal portion of the drain pipe 218 is perforated (not shown in FIG. 1G-1I) or hole, port, or perforation 174 on the sidewall 222 above it, as shown in FIG. 1J. May be provided. The hole, port, or perforation 174 provides additional space for drawing urine into the interior of the drainage tube 218, whereby even if the open distal end 220 of the drainage tube 218 is occluded. It can be ensured that fluid collection can continue. Also, the holes, ports, or perforations 174 can increase the surface area available for drawing fluid into the drain pipe 218, thereby increasing efficiency and / or fluid collection yield.

In some embodiments, the most distal portion of the support cap 212 may include a sponge such as a gel pad or pad 224. Pad 224 is positioned to contact and press against the upper bladder wall or bladder tissue 1004 for the purpose of preventing drainage, suction, or other trauma to the bladder 10 during negative pressure treatment. Can be

Referring to FIG. 1J, the bladder upper wall support 210 comprises a support cap 212 and a plurality of legs 214. As in the embodiments described above, the bladder upper wall support 210 is deployed to support the bladder upper wall in a retracted position where the support 210 is at least partially retracted within the conduit or tube 12. It is possible to move to and from the position. In some embodiments, the catheter device 10 also includes a drain tube 218 extending from the open distal end 30 of the conduit or tube 12. Unlike the embodiments described above, the support cap 212 shown in FIG. 4 comprises an inflatable balloon 226. The inflatable balloon 226 can be substantially hemispherical and comprises a curved distal surface 228 configured to contact and support at least a portion of the upper bladder wall or bladder tissue 1004 when deployed. be able to.

In some embodiments, the drain pipe 218 comprises a perforated portion 230 extending between the open distal end 30 of the pipe 12 and the support structure 212. The perforated portion 230 is positioned to draw the fluid into the interior of the drain tube 218 so that the fluid can be removed from the bladder 100. Desirably, the perforated portion 230 is positioned so that when negative pressure is applied there, it is not obstructed by either the deployed support cap 212 or the bladder wall. The discharge tube 218 may include or be positioned adjacent to an expansion tube 232 for providing fluid or gas to the interior 234 of the balloon 226 in order to inflate the balloon 226 from its contraction position to its deployment position. can. For example, as shown in FIG. 1J, the inflatable lumen 232 can be located within the drain pipe 218.

With reference to FIG. 1K, exemplary retention portions 6, 123 of the urine collection catheter device 10, comprising a plurality of coiled drainage lumens, generally represented as lumen 218, are illustrated. The retention portion 6 comprises a tube 12 having a distal open end 30. The drain lumen 218 is partially positioned within the tube 12. In the unfolded position, the drain lumen 218 is configured to extend from the open distal end 30 of the tube 12 and to conform to a coiled orientation. The drainage lumen 218 may be separate over the entire length of the catheter device 10 or may enter into a single drainage lumen defined by the tube 12. In some embodiments, as shown in FIG. 6, the drain lumen 218 can be a pigtail coil having one or more coils 244. Unlike the embodiments described above, the pigtail coil 244 is coiled around a shaft that is not the same as the shaft C of the non-coiled portion of the tube. Instead, as shown in FIG. 6, the pigtail coil may be coiled around an axis D that is substantially perpendicular to the axis C of the tube 12. In some embodiments, the drainage lumen 218 is a hole, port, or perforation similar to the perforations 132, 133 of FIG. 9A or 9B, in order to draw fluid from the bladder into the interior of the drainage lumen 218. (Not shown in FIG. 1K) can be provided. In some embodiments, the perforation can be located on the radial inward facing side 240 and / or the outward facing side of the coiled portion of the drainage lumen. As described above, perforations located on the radial inward facing side of the drainage lumen 218 or tube 12 are unlikely to be occluded by the bladder wall during the application of negative pressure to the bladder. .. Urine can also be drawn directly into one or more drainage lumens defined by the tube 12. For example, rather than being drawn into the drainage lumen 218 through the perforation 230, urine can be drawn directly through the open distal end 30 into the drainage lumen defined by the tube 12.

Referring to FIGS. 1L and 1M, another embodiment of the retention portion 123 is shown. The fluid receiving or distal end portion 30a of the catheter device 10a is shown in the contracted position in FIG. 1L and in the deployed position in FIG. 1M. The distal end 30a includes opposing bladder wall supports 19a, 19b to support the upper or lower bladder wall 1004. For example, the distal end portion 30a can include a proximal sheath 20a and a distal sheath 22a. Each sheath 20a, 22a extends between the slidable ring or collar 24a and the stationary or mounting ring or collar 28a. The sheaths 20a, 22a are formed from a flexible, non-porous material such as silicon or any of the materials discussed herein. The sheaths 20a, 22a are held together by one or more flexible wires or cables 26a. The sheaths 20a, 22a can also be connected by one or more rigid members such as the support 32a. In some embodiments, the support 32a can be a fork formed from a flexible shape memory material such as nickel titanium. The support 32a is positioned to provide support for the proximal sheath 20a and to prevent crushing when the distal end 30a is in the deployed position. In the retracted position, the collars 24a, 28a are positioned away from each other such that the sheaths 20a, 22a extend or fold relative to the cable 26a and the support 32a. In the unfolded position, the slidable collar 24a is moved towards the stationary collar 28a, allowing the sheaths 20a, 22a to be unfolded from the central cable 26a and to form a substantially flat disk-shaped structure. To.

In use, the distal end 30a of the catheter device 10a is inserted into the patient's bladder in the contracted position. Once inserted into the bladder, the distal sheath 22a is released by sliding the slidable collar 24a distally towards the stationary collar 28a. Once the distal sheath 22a is deployed, the proximal sheath 20a is released or deployed in a similar manner by sliding the slidable collar 24a proximally towards the individual stationary collar 28a. At this point, the proximal sheath 20a is floating within the bladder and is not positioned or sealed with respect to the inferior wall of the bladder. The pressure on the distal sheath 22a caused by the crushing of the bladder is transmitted through the support 32a to the proximal sheath 20a, moving the proximal sheath 20a towards the desired position adjacent to the opening of the urethra. Once the proximal sheath 20a is in place, a seal over the urethral opening may be created. The proximal sheath 20a helps maintain negative pressure in the bladder and prevents air and / or urine from exiting the bladder through the urethra.

Referring to FIG. 1N-1T, the retention portion 123 contacts the upper wall of the bladder 10 so that the bladder 10 contracts or does not occlude either the fluid port 312 of the catheter device 10 or the ureteral opening of the bladder. It comprises an inflatable support cap such as an annular balloon 310 that is positioned to prevent it. In some embodiments, the distal end portion 30 of the tube 12 extends through the central opening 314 of the balloon 310. The distal end portion 30 of the tube 12 can also contact the upper bladder wall.

Referring here to 1N and 1O, in some embodiments, the tube 12 comprises a fluid access portion 316 located proximal to the balloon 310 and extending through the sidewall of the tube 12. The fluid access portion 316 can include a filter 318 (shown in FIG. 1O) that is located centered on the central lumen of the tube 12. In some embodiments, the sponge material 320 can be positioned across the filter 318 due to the increased absorption of fluid in the bladder. For example, the sponge material 320 can be injection molded across the filter 318. During use, urine is absorbed by the sponge material 320 and passes through the filter 318 into the central lumen of the tube 12 in response to the application of negative pressure through the tube 12.

Here with reference to FIG. 1P-1R, in another embodiment, the support cap, such as the annular balloon 310, comprises a substantially spherical distal portion 322 configured to contact and support the upper bladder wall. .. The balloon 310 further comprises a plurality of proximally extending lobules 324. For example, the balloon 310 may include three foliate portions 324 equidistantly spaced around a portion of the tube 12 proximal to the balloon 310. As shown in FIG. 1R, the fluid port 312 can be located between adjacent foliate portions 324. In this configuration, the foliate portion 324 and the spherical distal portion 322 contact the bladder wall, which prevents the bladder wall from interfering with or obstructing the fluid port 312.

Referring here to FIGS. 1S and 1T, in another embodiment, the annular balloon 310 comprises a flat or elongated shape. For example, the annular balloon 310 is shown in FIG. 1T with a narrower portion 326 located adjacent to the tube 12 and an enlarged or spherical portion 328 positioned on its radial outward facing side. It can have a substantially teardrop-shaped radial cross section. When deployed within the bladder, the flat annular balloon 310 straddles the periphery of the trigone region of the bladder so that the outer circumference of the balloon 310 extends radially beyond the ureteral opening, optionally. , Constructed to seal it. For example, when positioned within the patient's bladder, the central opening 314 of the balloon 310 can be configured to be positioned above the triangular region. The fluid port 312 can be located proximal to the central partial balloon 310, as shown in FIG. 1T. Desirably, the fluid port 312 is located between the central opening 314 of the balloon and the triangular region. When the bladder contracts from the application of negative pressure, the bladder wall is supported by the outer circumference of the balloon 310 so as to avoid obstructing the ureteral opening. Therefore, in this configuration, the balloon 310 contacts the bladder wall and prevents it from interfering with or obstructing the fluid port 312. Similarly, as discussed herein, the balloon 310 keeps the triangular region open so that urine can be drawn from the ureter through the ureteral opening into the bladder.

Referring to FIG. 41, in another embodiment of the bladder catheter, the expandable cage 530 is capable of anchoring the bladder catheter within the bladder. The expandable cage 530 comprises a plurality of flexible members or apex extending longitudinally and radially outwardly from the catheter body of the bladder catheter, which in some embodiments is the ureter of FIG. 41. It can be similar to that discussed above with respect to the retention portion of the catheter. The member can be formed from a suitable elastic and shape memory material such as nitinol. In the unfolded position, the member or apex is provided with sufficient curvature to demarcate the spherical or ellipsoidal central cavity. The cage is attached to the open distal open end of the catheter tube or body to allow access to the drainage lumen defined by the tube or body. The cage is sized for positioning within the lower portion of the bladder and can define a diameter and length ranging from 1.0 cm to 2.3 cm, preferably about 1.9 cm (0.75 inches). ..

In some embodiments, the cage further comprises a shield or cover over the distal portion of the cage and the tissue, i.e., the distal wall of the bladder, is captured or bitten as a result of contact with the cage or member. Prevent or reduce the possibility of being. More specifically, as the bladder contracts, the medial distal wall of the bladder contacts the distal side of the cage. The cover may prevent tissue from being bitten or captured, reduce patient discomfort during use, and protect the device. The cover can be formed, at least in part, from a porous and / or permeable biocompatible material such as a woven polymer mesh. In some embodiments, the cover encloses all or substantially all of the cavity. In some embodiments, the cover covers only about 2/3, about half, or about 1/3 of the distal portion of the cage 210, or any amount.

The cage and cover can transition from a contracted position to a deployed position where the member is tightly contracted both around the central portion and / or around the bladder catheter 116, allowing insertion through the catheter or sheath. For example, in the case of a cage constructed from shape memory material, the cage can be configured to transition to a deployment position when heated to a sufficient temperature such as body temperature (eg, 37 ° C.). In the deployed position, the cage preferably has a diameter D, wider than the urethral opening, preventing patient movement from being transmitted to the ureter through the ureteral catheters 112, 114. The open arrangement of the member 212 or the apex does not interfere with or occlude the distal opening 248 and / or the drain port of the bladder catheter 216, making it easier to perform operations on the catheters 112, 114.

It should be understood that any of the bladder catheters described above may also be useful as a ureteral catheter.

The bladder catheter is connected to a vacuum source such as the pump assembly 710 by, for example, flexible tubes 166 defining the fluid flow path.
Illustrative fluid sensor:

Referring again to FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B, in some embodiments, the system or assembly 100, 700, 1100 is further from the ureters 6, 8 and / or the bladder 10. It comprises one or more sensors 174 for monitoring the physical parameters or fluid properties of the fluid or urine being collected. The one or more physiological sensors 174 associated with the patient can be configured to provide the controller with information representing at least one physical parameter. As discussed herein in connection with FIG. 44, the information obtained from the sensor 174 is transmitted to a central data acquisition module or processor, eg, an external device such as a pump 710 (shown in FIG. 44). Can be used to control the behavior of. The sensor 174 is integrally formed with one or more of the catheters 112, 114, 116, for example, embedded in the catheter body or the wall of the tube and in fluid communication with the drainage lumens 124, 140. be able to. In another embodiment, one or more of the sensors 174 can be located within the internal circuit of an external device such as a fluid collection vessel 712 (shown in FIG. 44) or a pump 710.

An exemplary sensor 174 that can be used in conjunction with the urine collection assembly 100 can include one or more of the following sensor types: For example, the catheter assembly 100 can include a conductivity sensor or electrode that samples the conductivity of urine. The normal conductivity of human urine is about 5-10 mS / m. Urine with a conductivity outside the expected range may indicate that the patient is suffering from a physiological problem and requires further treatment or analysis. The catheter assembly 100 can also be equipped with a flow meter for measuring the flow rate of urine through the catheters 112, 114, 116. The flow rate can be used to determine the total volume of fluid excreted from the body. Catheter 112, 114, 116 can also be equipped with a thermometer for measuring urine temperature. Urine temperature can be used to work with conductivity sensors. Urine temperature can also be used for monitoring purposes as it can indicate a physiological condition with urine temperature outside the normal physiological range. In some embodiments, the sensor 174 can be a urine sample sensor configured to measure the concentration of creatinine and / or protein in the urine. For example, various conductivity sensors and optical spectroscopy sensors may be used to determine sample concentration in urine. Sensors based on color change reagent test strips may also be used for this purpose.
How to insert the system:

Since the system 100 comprising a ureteral catheter and / or a ureteral stent and a bladder catheter has been described, some examples of methods for inserting and deploying a ureteral stent or ureteral catheter and bladder catheter are described. It will be discussed in detail here.

In some embodiments, a method for inducing negative pressure within a portion of the patient's urinary tract is provided, the method deploying a urinary catheter into the patient's urinary tract and with the patient's kidney. A step that maintains the patency of fluid flow between the bladder and the urinary bladder catheter comprises a distal portion and a proximal portion for insertion into the patient's kidney. In the step of deploying into the patient's bladder, the bladder catheter is the distal part for insertion into the patient's bladder and the proximal part for the application of negative pressure and is the patient's body. A step with an outwardly extending proximal portion and a step of applying negative pressure to the proximal end of the bladder catheter to induce negative pressure within a portion of the patient's urinary tract and remove fluid from the patient. including. In some embodiments, at least one of the ureteral or bladder catheters is (a) a proximal portion and (b) a distal portion, at least one protected drain, port, ... Or with a perforation to establish an outer peripheral edge or protective surface area that prevents mucosal tissue from obstructing at least one protected drain hole, port, or perforation in response to the application of negative pressure through the catheter. It is configured with a retention part and a distal part.

Referring to FIG. 42A, an example of a step for positioning the system within the patient's body and optionally inducing negative pressure into the patient's urinary tract such as the bladder, ureter, and / or kidney is illustrated. To. As shown in Box 610, a healthcare professional or caregiver inserts a flexible or rigid cystoscope into the bladder through the patient's urethra to obtain visibility of the meatus or opening. Once suitable visualization is obtained, the guidewire is advanced through the urethra, bladder, ureteral opening, ureter to the desired fluid collection position, such as the renal pelvis of the kidney, as shown in Box 612. Once the guidewire is advanced to the desired fluid collection position, the ureteral stent or ureteral catheter of the invention (the embodiments thereof are discussed in detail above) is a guide, as shown in Box 614. It is inserted into the fluid collection position across the wire. In some embodiments, the location of the ureteral stent or ureteral catheter can be confirmed by fluorescence fluoroscopy, as shown in Box 616. Once the location of the distal end of the ureteral stent or ureteral catheter is confirmed, the retention portion of the ureteral catheter can be deployed, as shown in Box 618. For example, the guide wire can be removed from the catheter, thereby allowing the distal end and / or retention portion to transition to the unfolded position. In some embodiments, the deployed distal end of the catheter completes the ureter and / or renal pelvis so that urine can pass from the outside of the catheter through the ureter into the bladder. Does not block. Moving the catheter can exert force on the ureteral tissue, thus avoiding complete obstruction of the ureter and avoiding the application of force to the side wall of the ureter, which can cause injury.

After the ureteral stent or catheter has come into place and deployed, the same guidewire will use the same insertion and positioning method described herein to provide a second ureteral stent or second. A ureteral catheter can be used to position another ureter and / or within the kidney. For example, a cystoscope can be used to obtain visualization of other ureteral openings in the bladder, and guidewires can be placed at fluid collection locations in other ureters through the visualized ureteral openings. You can move forward. The second ureteral stent or second ureteral catheter can be towed with a guide wire and deployed in the manner described herein. Alternatively, the cystoscope and guidewire can be removed from the body. The cystoscope can be reinserted into the bladder over the first ureteral catheter. The cystoscope obtains visibility of the ureteral opening and advances the second guidewire to the second ureter and / or kidney to position the second ureteral stent or second ureteral catheter. Used in the manner described above to aid in this. Once the ureteral stent or catheter is in place, in some embodiments the guidewire and cystoscope are removed. In other embodiments, the cystoscope and / or guidewire can remain in the bladder and assist in the placement of the bladder catheter.

In some embodiments, once the ureteral catheter is in place, the healthcare professional, caregiver, or patient has the patient at the distal end of the bladder catheter in a crushed or contracted state, as shown in Box 620. Can be inserted into the bladder through the urethra. The bladder catheter can be the bladder catheter of the invention as discussed in detail above. Once inserted into the bladder, the anchor connected to and / or associated with the bladder catheter is extended to the deployment position, as shown in Box 622. In some embodiments, the bladder catheter is inserted into the bladder through the urethra without the use of guide wires and / or cystoscopes. In another embodiment, the bladder catheter is inserted over the same guide wire used to position the ureteral stent or catheter.

In some embodiments, the ureteral stent or ureteral catheter is deployed and remains in the patient's body for at least 24 hours or longer. In some embodiments, the ureteral stent or ureteral catheter is deployed and stays in the patient's body for at least 30 days or longer. In some embodiments, the ureteral stent or ureteral catheter can be replaced periodically, eg, weekly or monthly, to extend the duration of therapy.

In some embodiments, the bladder catheter is replaced more frequently than a ureteral stent or ureteral catheter. In some embodiments, multiple bladder catheters are continuously installed and removed during the indwelling time for a single ureteral stent or ureteral catheter. For example, a doctor, nurse, caregiver, or patient can place a bladder catheter within the patient at home or in any health care setting. Multiple bladder catheters are provided within the kit, optionally, with instructions for installation, replacement, and optional connection of the bladder catheter and negative pressure source or drainage into the container, along with healthcare professionals, patients, Or it can be provided to the caregiver. In some embodiments, the negative pressure is applied nightly over a predetermined number of nights (such as 1-30 nights or more). Optionally, the bladder catheter can be replaced every night prior to the application of negative pressure.

In some embodiments, urine is allowed to drain by gravity or peristalsis from the urethra. In another example, negative pressure is induced within the bladder catheter and promotes urine drainage. Although not intended to be constrained by any theory, some of the negative pressure applied to the proximal end of the bladder catheter is transmitted to the ureter, renal pelvis, or other parts of the kidney and from the kidney. It is thought to promote the excretion of fluid or urine.

With reference to FIG. 42B, steps for using the system for inducing negative pressure in the ureter and / or kidney are illustrated. As shown in Box 624, the ureteral stent or indwelling portion of the ureteral catheter and bladder catheter is properly positioned and any mooring / retention structure, if present, is deployed externally proximal to the bladder catheter. The ends are connected to the fluid collection or pump assembly. For example, a bladder catheter can be connected to a pump to induce negative pressure in the patient's bladder, renal pelvis, and / or kidney.

Once the bladder catheter and pump assembly are connected, negative pressure is applied to the renal pelvis and / or kidney and / or bladder through the drainage lumen of the bladder catheter, as shown in Box 626. Negative pressure is intended to counter stasis-mediated interstitial hydrostatic pressure due to elevated intra-abdominal pressure and consequent or elevated renal venous or lymphatic pressure. The applied negative pressure can therefore increase the flow of filtrate through the medullary tubules and reduce water and sodium reabsorption.

As a result of the applied negative pressure, urine is drawn into the bladder catheter at its distal end drain port, through the bladder catheter drain lumen, into a fluid collection vessel for disposal, as shown in Box 628. Is done. As urine is drawn into the collection vessel, in box 630, any sensor placed within the fluid collection system can be used to assess physical parameters such as the volume of urine collected. And information about the physical condition of the patient and the composition of the urine produced can be provided. In some embodiments, the information acquired by the sensor is processed by a processor associated with a pump and / or another patient monitoring device, as shown in Box 632, and in Box 634, the associated feedback device. Shown to the user through the visual display of.
Illustrative fluid collection system:

Illustrative systems and methods for positioning such systems within the patient's body have been described here, with reference to FIG. 44, inducing negative pressure into the patient's bladder, ureter, renal pelvis, and / or kidney. A system 700 for this will be described. The system 700 can include a ureteral stent and / or a ureteral catheter, a bladder catheter, or system 100 as described above herein. As shown in FIG. 44, the bladder catheter 116 of the system 100 is connected to one or more fluid collection containers 712 to collect urine drawn from the bladder. A fluid collection vessel 712 connected to the bladder catheter 116 is an external fluid pump 710 and fluid to generate negative pressure through the bladder catheter 116 and / or the ureteral catheters 112, 114 into the bladder, ureter, and / or kidney. Can communicate. As discussed herein, such negative pressure can be provided to overcome interstitial pressure and form urine within the kidney or renal unit. In some embodiments, the connection between the fluid collection vessel 712 and the pump 710 is equipped with a fluid lock or fluid barrier, and in the case of accidental therapeutic or non-therapeutic pressure changes, the air is in the bladder, renal pelvis, or. It can be prevented from entering the kidney. For example, the inflow and outflow ports of a fluid vessel can be located within the vessel below the fluid level. Therefore, air is prevented from entering the medical tube or catheter through either the inflow or outflow port of the fluid container 712. As discussed above, the outer portion of the tubing extending between the fluid collection vessel 712 and the pump 710 includes one or more filters and does not allow urine and / or particulate matter to enter the pump 710. Can be prevented.

As shown in FIG. 44, the system 700 is further electronically coupled to the pump 710 and comprises a controller 714 such as a microprocessor having or associated with a computer-readable memory 716. In some embodiments, the memory 716, when executed, comprises an instruction to cause the controller 714 to receive information from a sensor 174 located on or associated with a portion of the assembly 100. Information about the patient's condition can be determined based on the information from the sensor 174. Information from sensor 174 can also be used to determine and implement operating parameters for pump 710.

In some embodiments, the controller 714 is integrated within a separate and remote electronic device that communicates with a pump 710 such as a dedicated electronic device, computer, tablet PC, or smartphone. Alternatively, the controller 714 can be contained within the pump 710, for example, both a user interface for manually operating the pump 710 and system functions such as receiving and processing information from the sensor 174. Can be controlled.

The controller 714 is configured to receive information from one or more sensors 174 and store the information in associated computer-readable memory 716. For example, the controller 714 can be configured to receive information from the sensor 174 at a predetermined rate, such as once per second, and determine the conductivity based on the received information. In some embodiments, the algorithm for calculating conductivity also includes other sensor measurements such as urine temperature to obtain a more robust determination of conductivity.

The controller 714 can also be configured to calculate patient physical statistics or diagnostic indicators that illustrate changes in the patient's condition over time. For example, the system 700 can be configured to identify the total amount of sodium excreted. The total amount of sodium excreted can be based, for example, on a combination of flow rate and conductivity over a period of time.

With reference to FIG. 44 continuously, the system 700 may further include a feedback device 720, such as a visual display or an audio system, to provide information to the user. In some embodiments, the feedback device 720 can be integrally formed with the pump 710. Alternatively, the feedback device 720 can be a separate dedicated or multipurpose electronic device such as a computer, laptop computer, tablet PC, smartphone, or other handheld electronic device. The feedback device 720 is configured to receive a calculated or determined measurement from the controller 714 and present the received information to the user via the feedback device 720. For example, the feedback device 720 may be configured to display the current negative pressure (in mmHg units) applied to the urinary tract. In another embodiment, the feedback device 720 is the current urine flow rate, temperature, current conductivity in mS / m units of urine, total urine volume produced during the session, excreted during the session. It is configured to display the total amount of sodium, other physical parameters, or any combination thereof.

In some embodiments, the feedback device 720 further comprises a user interface module or component that allows the user to control the operation of the pump 710. For example, the user can turn the pump 710 on or off via the user interface. The user can also adjust the pressure applied by the pump 710 to achieve greater magnitude or rate of sodium excretion and fluid removal.

Optionally, the feedback device 720 and / or the pump 710 further comprises a data transmitter 722 for transmitting information from the device 720 and / or the pump 710 to another electronic device or computer network. The data transmitter 722 can utilize short-range or long-range data communication protocols. An example of a short-range data transmission protocol is Bluetooth®. Long-distance data transmission networks include, for example, Wi-Fi or cellular networks. The data transmitter 722 can transmit information to the patient's doctor or caregiver to inform the doctor or caregiver about the patient's current condition. Alternatively, or in addition, the information can be transmitted from the data transmitter 722 to an existing database or information storage location, eg, to include information recorded in the patient's electronic medical record (EHR). ..

With reference to FIG. 44 continuously, in addition to the urine sensor 174, in some embodiments, the system 700 may further include one or more patient monitoring sensors 724. The patient monitoring sensor 724 is a urine composition, blood composition (eg, hematocrit rate, sample concentration, protein concentration, creatinine concentration) and / or blood flow (eg, blood pressure, blood flow velocity) as discussed in detail above. Invasive and non-invasive sensors can be included to measure information about the physical parameters of the patient, such as. Hematocrit is the ratio of the volume of red blood cells to the total volume of blood. Normal hematocrit is about 25% to 40%, preferably about 35% and 40% (eg, 35% to 40% erythrocytes by volume and 60% to 65% plasma).

The non-invasive patient monitoring sensor 724 can include a pulse oximetry sensor, a blood pressure sensor, a heart rate sensor, and a respiratory sensor (eg, a capnography sensor). The invasive patient monitoring sensor 724 can include an invasive blood pressure sensor, a glucose sensor, a blood velocity sensor, a hemoglobin sensor, a hematocrit sensor, a protein sensor, a creatinine sensor, and the like. In yet another embodiment, the sensor may be associated with an extracorporeal blood system or circuit and configured to measure the parameters of blood passing through the tubes of the extracorporeal system. For example, a specimen sensor such as a capacitance sensor or an optical spectroscopy sensor may be associated with a tube of an extracorporeal blood system and may measure a parameter value of the patient's blood as it passes through the tube. The patient monitoring sensor 724 can communicate wiredly or wirelessly with the pump 710 and / or the controller 714.

In some embodiments, the controller 714 is configured to cause the pump 710 to provide treatment for patient-based information obtained from a urine sample sensor 174 and / or a patient monitoring sensor 724, such as a blood monitoring sensor. To. For example, the operating parameters of the pump 710 can be adjusted based on changes in the patient's blood hematocrit rate, blood protein concentration, creatinine concentration, micturition volume, urinary protein concentration (eg albumin), and other parameters. For example, the controller 714 can be configured to receive information about the patient's blood hematocrit rate or creatinine concentration from the patient monitoring sensor 724 and / or the sample sensor 174. The controller 714 can be configured to adjust the operating parameters of the pump 710 based on blood and / or urine measurements. In another example, the hematocrit rate may be measured from a blood sample periodically taken from the patient. The test results can be manually or automatically provided to controller 714 for processing and analysis.

As discussed herein, the measured hematocrit values for a patient can be compared to a given threshold or clinically acceptable value for a general population. In general, hematocrit levels for women are lower than those for men. In other examples, the measured hematocrit value can be compared to the patient baseline value obtained prior to the surgical procedure. When the measured hematocrit value is increased within an acceptable range, the pump 710 may be turned off and the application of negative pressure to the ureter or kidney may be stopped. Similarly, the intensity of the negative pressure can be adjusted based on the measured parameter values. For example, the intensity of negative pressure applied to the ureter and kidney can be reduced as the patient's measured parameters begin to approach an acceptable range. In contrast, when undesired tendencies (eg, decreased hematocrit, micturition, and / or creatinine clearance) are identified, the intensity of negative pressure is increased to produce positive physiological results. Can be done. For example, the pump 710 may be configured to start by providing a low level of negative pressure (eg, about 0.1 mmHg to 10 mmHg). Negative pressure may be gradually increased until a positive trend in patient creatinine levels is observed. However, in general, the negative pressure provided by the pump 710 will not exceed about 50 mmHg.

With reference to FIGS. 45A and 45B, an exemplary pump 710 for use with the system is illustrated. In some embodiments, the pump 710 is configured to draw fluid from catheters 112, 114 (eg, shown in FIGS. 1A, 1B, 1C, 1F, 1P, 1U, 2A, 2B) and is about 10 mmHg or A micropump with less sensitivity or accuracy. Desirably, the pump 710 can provide a urine flow range of 0.05 ml / min to 3 ml / min over a long period of time, eg, about 8 hours to about 24 hours / day, 1 to about 30 days, or longer. Is. At 0.2 ml / min, it is expected that approximately 300 mL of urine / day will be collected by System 700. The pump 710 can be configured to provide a negative pressure to the patient's bladder, the negative pressure being about 0.1 mmHg to about 150 mmHg, or about 0.1 mmHg to about 50 mmHg, or about 5 mmHg to 20 mmHg (pump). Gauge pressure at 710). For example, Ranger Inc. The micropump manufactured by (Model BT100-2J) can be used in combination with the system 700 of the present disclosure. Diaphragm aspirator pumps as well as other types of commercially available pumps can also be used for this purpose. Peristaltic pumps can also be used in conjunction with System 700. In other embodiments, a piston pump, vacuum bottle, or manual vacuum source can be used to provide negative pressure. In another embodiment, the system can be connected to a wall suction source, such as that available in hospitals, through a vacuum regulator to reduce negative pressure to therapeutically appropriate levels.

In some embodiments, at least a portion of the pump assembly can be located in the patient's urinary tract, eg, in the bladder. For example, the pump assembly may include a pump module and a control module coupled to the pump module, the control module being configured to direct the movement of the pump module. At least one (one or more) of pump modules, control modules, or power sources may be located in the patient's urinary tract. The pump module is positioned within the fluid flow channel and can include at least one pump element that draws fluid through the channel. Some examples of suitable pump assemblies, systems, and methods of use are entitled "Indwelling Pump for Facilitating Removal of Urine from Urinary Tract", US Patent Application No. 62, filed August 25, 2017. / 550, 259 (incorporated herein as a whole by reference).

In some embodiments, the pump 710 is configured for long-term use and therefore, excluding the bladder catheter replacement time, for example, about 8 hours to about 24 hours / day, or 1 to about 30 days, or more. It is possible to maintain precise suction over a long period of time. Further, in some embodiments, the pump 710 is manually operated and is configured to include a control panel 718 that allows the user to set the desired suction value. The pump 710 can also include a controller or processor that can be the same controller that operates the system 700, or can be a separate processor dedicated to the operation of the pump 710. In either case, the processor is configured to receive instructions both for manual operation of the pump and for automatic operation of the pump 710 according to predetermined operating parameters. Alternatively, or in addition, the operation of the pump 710 can be controlled by the processor based on the feedback received from multiple sensors associated with the catheter.

In some embodiments, the processor is configured to operate the pump 710 intermittently. For example, the pump 710 may be configured to emit a pulse of negative pressure for a period of no negative pressure. In another embodiment, the pump 710 can be configured to alternate between providing negative and positive pressures to provide alternating flush and pump effects. For example, a positive pressure of about 0.1 mmHg to 20 mmHg, preferably about 5 mmHg to 20 mmHg, can be provided followed by a negative pressure ranging from about 0.1 mmHg to 50 mmHg.

The steps for removing excess fluid from a patient using the devices and systems described herein are illustrated in FIG. As shown in FIG. 49, the treatment method is to use a ureteral catheter such as a ureteral stent or ureteral catheter to allow the ureter to flow from the ureter and / or the kidney, as shown in Box 910. Includes steps to deploy in the ureter and / or kidney. The catheter may be placed to avoid obstruction of the ureter and / or kidney. In some embodiments, the fluid collection portion of the stent or catheter may be located within the renal pelvis of the patient's kidney. In some embodiments, the ureteral stent or ureteral catheter may be located within each of the patient's kidneys. In another embodiment, the urine collection catheter may be deployed in the bladder or urinary tract as shown in Box 911. In some embodiments, the ureteral catheter comprises one or more of any of the retention portions described herein. For example, a ureteral catheter can include a tube that defines a drainage lumen with a helical retention portion and a plurality of drainage ports. In another embodiment, the catheter can include a funnel-shaped fluid collection and retention portion or pigtail coil. Alternatively, for example, a ureteral stent with a pigtail coil can be deployed.

As shown in Box 912, the method further applies negative pressure to at least one of the bladder, ureter, and / or kidney through a bladder catheter to induce or induce fluid or urine production in the kidney. Includes steps to promote and extract fluid or urine from the patient. Desirably, the negative pressure is applied over a period of time sufficient to reduce the patient's blood creatinine levels by a clinically significant amount.

The negative pressure may continue to be applied over a predetermined period of time. For example, the user may be instructed to operate the pump over a period of time selected based on the duration of the surgical procedure or the physiological characteristics of the patient. In other embodiments, the patient's condition may be monitored to determine when adequate treatment is provided. For example, as shown in Box 914, the method may further include monitoring the patient and determining when to stop applying negative pressure to the patient's bladder, ureter, and / or kidney. .. In some examples, the hematocrit level of the patient is measured. For example, a patient monitoring device may be used to periodically obtain hematocrit values. In other examples, blood samples may be taken periodically and hematocrit may be measured directly. In some examples, the concentration and / or volume of urine excreted from the body through the bladder catheter may also be monitored to determine the rate at which urine is produced by the kidneys. Similarly, excreted urination may be monitored to determine protein concentration and / or creatinine clearance rate for the patient. Reduced creatinine and protein concentrations in urine may indicate overdilution and / or decreased renal function. The measured values are compared to a given threshold to assess whether negative pressure therapy improves the patient's condition and should be corrected or discontinued. For example, as discussed herein, the desired range for patient hematocrit may be 25% -40%. In other embodiments, patient weight may be measured and compared to dry weight, as described herein. The measured changes in patient weight demonstrate that the fluid is being removed from the body. Therefore, a return to dry body weight indicates that the blood dilution is well controlled and the patient is not overdiluted.

As shown in Box 916, the user may stop the pump from providing negative pressure therapy once a positive result is identified. Similarly, patient blood parameters may be monitored to assess the effectiveness of the negative pressure applied to the patient's kidneys. For example, the capacitance or sample sensor may be installed to communicate fluid with the tubes of the extracorporeal blood management system. Sensors may be used to measure information representing blood protein, oxygen, creatinine, and / or hematocrit levels. The measured blood parameter values may be measured persistently or periodically and compared to various thresholds or clinically acceptable values. Negative pressure may continue to be applied to the patient's bladder, kidney, or ureter until the measured parameter values are clinically acceptable. Once the measured value is within the threshold or clinically acceptable range, the application of negative pressure may be stopped, as shown in Box 916.

In some embodiments, methods are provided for removing excess fluid from a patient for systemic fluid volume management associated with chronic edema, hypertension, chronic kidney disease, and / or acute heart failure. According to another aspect of the present disclosure, there is provided a method for removing excess fluid for a patient undergoing a resuscitation fluid procedure such as coronary transplant bypass surgery by removing the excess fluid from the patient. During the resuscitation infusion, a solution such as an aqueous solution of physiological saline and / or a solution of starch is introduced into the patient's bloodstream by a suitable fluid delivery process such as an intravenous drip. For example, in some surgical procedures, the patient may be supplied with a normal fluid daily intake 5-10 times. Fluid replacement or resuscitation fluids may be provided to replenish fluid lost through sweating, bleeding, dehydration, and similar processes. For surgical procedures such as coronary transplant bypass, resuscitation fluids are provided to help maintain the patient's fluid balance and blood pressure within appropriate rates. Acute kidney injury (AKI) is a known complication of coronary transplant bypass surgery. AKI is associated with long-term hospitalization and increased morbidity and mortality, even in patients who do not progress to renal failure. Kim, et al. , Relationship beween a perioperative intravenous fluid administration strategy and acte kidney injury following off-pump corporary stery Introducing fluid into the blood also reduces hematocrit levels, which have been shown to further increase mortality and morbidity. Studies have also demonstrated that the introduction of aqueous saline solutions into patients can reduce renal function and / or interfere with natural fluid management processes. Therefore, proper monitoring and control of renal function can produce improved outcomes, especially reducing postoperative cases of AKI.

A method of treating a patient to remove excess fluid is illustrated in FIG. As shown in Box 1010, the method uses a ureteral stent or ureteral catheter to prevent the flow of urine from the ureter and / or kidney from obstruction of the ureter and / or kidney. Includes steps to deploy in the ureter and / or kidney. For example, the distal end of the ureteral stent or fluid collection portion of the catheter may be located within the renal pelvis. In other embodiments, the catheter may be deployed in the kidney or urinary tract. The catheter can comprise one or more of the ureteral catheters described herein. For example, the catheter can comprise a tube that defines a drainage lumen and has a helical retention portion and multiple drainage ports. In another embodiment, the catheter can include a pigtail coil.

As shown in Box 1012, the bladder catheter can be deployed within the patient's bladder. For example, a bladder catheter may be positioned to seal the urethral opening at least partially and prevent the passage of urine from the body through the urethra. The bladder catheter can include, for example, an anchor to maintain the distal end of the catheter within the bladder. As described herein, coils and other sequences such as spirals, funnels, etc. may be used to obtain proper positioning of the bladder catheter. The bladder catheter should collect not only the fluid that has entered the patient's bladder prior to the installation of the ureteral catheter, but also the fluid that is collected from the ureter, ureteral stent, and / or ureteral catheter during treatment. Can be configured in. The bladder catheter may also collect urine that flows past the fluid collection portion of the ureteral catheter and enters the bladder. In some embodiments, the proximal portion of the ureteral catheter may be located within the drainage lumen of the bladder catheter. Similarly, the bladder catheter may be advanced into the bladder using the same guide wire used to position the ureteral catheter. In some embodiments, negative pressure may be provided to the bladder through the drainage lumen of the bladder catheter. In other embodiments, the negative pressure may be applied only to the bladder catheter. In that case, the ureteral catheter is drained into the bladder by gravity.

As shown in Box 1014, following deployment of the ureteral stent and / or ureteral catheter and bladder catheter, negative pressure is applied to the bladder, ureter, and / or kidney through the bladder catheter. For example, negative pressure can be applied over a period sufficient to extract urine containing a portion of the fluid provided to the patient during the resuscitation infusion procedure. As described herein, negative pressure can be provided by an external pump connected to the proximal end or port of the bladder catheter. The pump can be operated continuously or periodically, depending on the patient's therapeutic requirements. In some cases, the pump may alternate between the application of negative pressure and the application of positive pressure.

The negative pressure may continue to be applied over a predetermined period of time. For example, the user may be instructed to operate the pump over a period of time selected based on the duration of the surgical procedure or the physiological characteristics of the patient. In other embodiments, the patient's condition may be monitored to determine when a sufficient amount of fluid has been withdrawn from the patient. For example, as shown in Box 1016, the fluid discharged from the body may be collected and the total volume of the acquired fluid may be monitored. In that case, the pump can continue to operate until a given fluid volume has been collected from the ureter and / or bladder catheter. The predetermined fluid volume may be based, for example, on the volume of fluid provided to the patient prior to and during the surgical procedure. As shown in Box 1018, the application of negative pressure to the bladder, ureter, and / or kidney is stopped when the total volume of collected fluid exceeds a predetermined fluid volume.

In other embodiments, pump operation can be determined based on the patient's measured physiological parameters such as measured creatinine clearance, blood creatinine levels, or hematocrit rate. For example, as shown in Box 1020, urine collected from a patient may be analyzed by one or more sensors associated with a catheter and / or pump. The sensor can be a capacitance sensor, a sample sensor, an optical sensor, or a similar device configured to measure urine sample concentration. Similarly, as shown in Box 1022, a patient's blood creatinine or hematocrit levels can be analyzed based on the information obtained from the patient monitoring sensors discussed above herein. For example, the capacitance sensor may be installed in an existing extracorporeal blood system. The information acquired by the capacitance sensor may be analyzed to determine the patient's hematocrit rate. The measured hematocrit rate may be compared to some expected or therapeutically acceptable value. The pump may continue to apply negative pressure to the patient's ureter and / or kidney until a measured value within the therapeutically acceptable range is obtained. Once a therapeutically acceptable value is obtained, the application of negative pressure may be stopped, as shown in Box 1018.

In another example, as shown in Box 2024, it may be assessed whether the patient's body weight has been measured and removed from the patient by negative pressure therapy to which fluid is applied. For example, the patient's measured body weight, including the fluid introduced during the resuscitation infusion procedure, can be compared to the patient's dry weight. As used herein, dry body weight is defined as normal body weight as measured when the patient is not overdiluted. For example, patients who do not have one or more of elevated blood pressure, stunned or muscle cramps, swelling around the legs, feet, arms, hands, or eyes and are breathing comfortably are in excess. Most likely it does not have fluid. The weight measured when the patient does not suffer from such symptoms can be dry weight. The patient's body weight can be measured periodically until the measured body weight approaches the dry body weight. As shown in Box 1018, the application of negative pressure can be stopped when approaching the measured body weight (eg, within 5% to 10% of the dry body weight).

The aforementioned details of treatment using the system of the invention can be used to treat a variety of medical conditions that may benefit from increased urine or fluid output or removal. For example, to preserve renal function by applying negative pressure, reduce interstitial pressure in the renal tubules, promote urination, and prevent venous stasis-induced renal unit hypoxia in the renal medullary. The method is provided. The method involves deploying a ureteral stent or ureteral catheter into the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder, and the bladder catheter of the patient. A step that deploys into the bladder, the bladder catheter extends between and between the distal and proximal ends of the drainage ureter, configured to be located within the patient's bladder. A step of applying negative pressure to the proximal end of the catheter, inducing negative pressure into a portion of the patient's ureter and removing fluid from the patient's ureter over a predetermined period of time. And include.

In another embodiment, a method for the treatment of acute renal injury due to venous stasis is provided. The method involves deploying a ureteral stent or ureteral catheter into the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder, and the bladder catheter of the patient. A step that deploys into the bladder, the bladder catheter extends between and between the distal and proximal ends of the drainage ureter, configured to be located within the patient's bladder. A step, with a side wall, and a negative pressure applied to the proximal end of the catheter to induce a negative pressure into a portion of the patient's ureter over a predetermined period of time, removing fluid from the patient's ureter. Thereby, it includes steps to reduce venous stagnation in the kidney and treat acute renal injury.

In another embodiment, methods for the treatment of New York Heart Association (NYHA) Classification III and / or Classification IV heart failure through reduction of venous stasis in the kidney are provided. The method involves deploying a ureteral stent or ureteral catheter into the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder, and the bladder catheter of the patient. A step that deploys into the bladder, the bladder catheter extends between and between the distal and proximal ends of the drainage ureter, configured to be located within the patient's bladder. A step, with a side wall, and a negative pressure applied to the proximal end of the catheter to induce a negative pressure into a portion of the patient's ureter over a predetermined period of time, removing fluid from the patient's ureter. Includes steps to treat excess fluid in NYHA classification III and / or classification IV heart failure.

In another embodiment, methods for the treatment of stage 4 and / or stage 5 chronic kidney disease through reduction of venous stasis in the kidney are provided. The method involves deploying a ureteral stent or ureteral catheter into the patient's ureter or kidney to maintain patency of fluid flow between the patient's kidney and bladder, and the bladder catheter of the patient. A step that deploys into the bladder, the bladder catheter extends between and between the distal and proximal ends of the drainage ureter, configured to be located within the patient's bladder. A step, with a side wall, and a negative pressure applied to the proximal end of the catheter, inducing a negative pressure into part of the patient's ureter, removing fluid from the patient's ureter, and venous stasis in the kidney. Includes steps to reduce.

In some embodiments, the kit is provided to remove fluid from the patient's urinary tract and / or induce negative pressure within a portion of the patient's urinary tract. The kit includes a ureteral stent or catheter with a drainage channel to facilitate fluid flow from the ureter and / or kidney through the drainage channel of the ureteral stent or catheter towards the patient's bladder, and negative. A pump with a controller configured to induce pressure within at least one of the patient's ureter, kidney, or bladder and to draw urine through the drainage lumen of a catheter deployed within the patient's ureter. And. In some embodiments, the kit further comprises at least one bladder catheter. In some embodiments, the kit further operates one or more of the following: ureteral stents and / or ureteral catheters to insert / deploy, bladder catheters to insert / deploy, and pumps. And equipped with instructions to draw urine through the drainage lumen of a bladder catheter deployed within the patient's bladder.

In some embodiments, another kit is a plurality of disposable bladder catheters, each bladder catheter having a proximal end and a distal end configured to be positioned within the patient's bladder, and between them. Extends radially outward from a portion of the drainage canal with a side wall and a portion of the distal end of the drainage canal, and the diameter of the retention section exceeds the diameter of the drainage canal. Multiple disposable bladder catheters, with retention portions configured to extend into the deployment position, instructions for inserting / deploying the bladder catheter, and the proximal end of the bladder catheter to the pump. It comprises instructions to operate the pump to connect and, for example, by applying a negative pressure to the proximal end of the bladder catheter, to draw urine through the drainage lumen of the bladder catheter.

In some embodiments, kits are provided, wherein the kit is a plurality of disposable bladder catheters, each bladder catheter being (a) a proximal portion and (b) a distal portion, at least one. A protected drain, port, or perforation that prevents mucosal tissue from obstructing at least one protected drain, port, or perforation in response to the application of negative pressure through the catheter. Multiple disposable bladder catheters with retaining portions, distal portions, configured to establish an outer margin or protective surface area, instructions for deploying the bladder catheter, and the proximal end of the bladder catheter. It is equipped with instructions to connect to the pump and to operate the pump and draw urine through the drainage lumen of the bladder catheter.
Experimental Example of Inducing Negative Pressure Using a Ureteral Catheter:

Induction of negative pressure in the renal pelvis of domestic pigs was performed for the purpose of assessing the effect of negative pressure therapy on renal stasis in the kidney. The purpose of these studies was to demonstrate whether the negative pressure delivered into the renal pelvis significantly increased micturition in a pig model of renal stasis. In Example 1, a pediatric Fogarty catheter, commonly used in embolectomy or bronchoscopy applications, was used in the pig model solely for evidence of the principle of induction of negative pressure in the renal pelvis. It is not suggested that Fogarty catheters will be used in humans in clinical settings to avoid injury to urinary tract tissue. In Example 2, a ureteral catheter 112, shown in FIGS. 2A and 2B, was used, comprising a spiral retention portion for mounting or maintaining the distal portion of the catheter in the renal pelvis or kidney.
(Example 1)
Method

Four domestic pigs 800 were used for the purpose of assessing the effect of negative pressure therapy on renal stasis in the kidney. As shown in FIG. 21, pediatric Fogarty catheters 812, 814 were inserted into the renal pelvis regions 820, 821 of the kidneys 802, 804 of the four pigs 800, respectively. Catheter 812, 814 were deployed within the renal pelvis region by inflating the expandable balloon to a size sufficient to seal the renal pelvis and maintain the position of the balloon within the renal pelvis. Catheter 812, 814 extend from the renal pelvis 802, 804 through the bladder 810 and urethra 816 to the fluid collection vessel outside the pig.

Urination of two animals was collected over a 15 minute period to establish a baseline for micturition volume and rate. Urination of the right kidney 802 and the left kidney 804 was measured individually and found to be significantly variable. Glomerular clearance values were also determined.

Renal stagnation (eg, venous stagnation or reduced blood flow in the kidney) partially occludes the inferior vena cava (IVC) with an inflatable balloon catheter 850 just above the renal venous outlet, to the right of animal 800. It was induced in the kidney 802 and the left kidney 804. A pressure sensor was used to measure the IVC pressure. The normal IVC pressure was 1-4 mmHg. By inflating the balloon of catheter 850 to about 3/4 of the IVC diameter, the IVC pressure was increased to 15-25 mmHg. Inflating the balloon up to about 3/4 of the IVC diameter resulted in a 50-85% reduction in urination. Complete occlusion generated IVC pressure above 28 mmHg and was associated with a at least 95% reduction in micturition.

One kidney of each animal 800 was untreated and donated as a control ("control kidney 802"). A ureteral catheter 812 extending from the control kidney was connected to a fluid collection vessel 819 to determine fluid levels. One kidney in each animal (“therapeutic kidney 804”) is combined with a negative pressure source (eg, a regulator designed to more accurately control small magnitude negative pressure) connected to the ureteral catheter 814. He was treated with negative pressure from the therapy pump 818). The pump 818 was an Air Catet Vacuum Pump manufactured by Core-Parmer Instrument Company (model number EW-07530-85). The pump 818 was connected in series with the regulator. The regulator is Airtrol Components Inc. It was manufactured by V-800 Series Precision Precision Vacuum Regulator-1 / 8 NPT Ports (model number V-800-10-W / K).

Pump 818 was operated to induce negative pressure within the renal pelvis 820, 821 of the treated kidney according to the following protocol. First, the effect of negative pressure was investigated under normal conditions (eg, without inflating the IVC balloon). Four different pressure levels (-2, -10, -15, and -20 mmHg) were applied 15 minutes each to determine the rate of urine and creatinine clearance produced. The pressure level was controlled and determined in the regulator. Following -20 mmHg therapy, the IVC balloon was inflated, increasing the pressure by 15-20 mmHg. The same four negative pressure levels were applied. Urination volume and creatinine clearance rate for stasis control kidney 802 and treatment kidney 804 were obtained. Animal 800 was stasis by a 90 minute partial occlusion of IVC. Treatment was provided over 60 minutes of the 90-minute stasis period.

Following urination and collection of creatinine clearance data, kidneys from one animal underwent gross examination and were then immobilized in 10% neutral buffered formalin. Following macroscopic examination, tissue sections were obtained and examined, and magnified images of the sections were captured. Sections were inspected using an upright Olympus BX41 optical microscope and images were captured using an Olympus DP25 digital camera. Specifically, the light micrograph image of the sampled tissue was acquired at a low magnification (20x original magnification) and a high magnification (100x original magnification). The images obtained received a histological evaluation. The purpose of the evaluation was to histologically examine the tissue and qualitatively characterize the stasis and tubular degeneration of the obtained sample.

Surface mapping analysis was also performed on the acquired slides of kidney tissue. Specifically, samples were stained and analyzed to assess differences in tubular size for treated and untreated kidneys. Image processing techniques were used to calculate the number and / or relative percentage of pixels with different tints in the stained image. The calculated measurement data were used to determine the volume of different anatomical structures.
Results Urination and creatinine clearance

The amount of urination varied significantly. The causes of three variations in micturition volume were observed during the study. Fluctuations between individuals and hemodynamics were the expected causes of variations known in the art. A third cause of variability in urination is contralateral intra-individual variability in urination identified in the experiments discussed herein, based on information and ideas previously unknown. ..

Baseline micturition was 0.79 ml / min for one kidney and 1.07 ml / min for the other kidney (eg, 26% difference). The amount of urination is an equal temperament calculated from the amount of urination for each animal.

When the stasis was provided by inflating the IVC balloon, the treated renal micturition dropped from 0.79 ml / min to 0.12 ml / min (15.2% of baseline). By comparison, control renal micturition during stasis dropped from 1.07 ml / min to 0.09 ml / min (8.4% of baseline). Based on micturition volume, the relative increase in treated renal micturition compared to control renal micturition was calculated according to the following equation.
(Therapeutic treatment / baseline treatment) / (Therapeutic control / baseline control) = Relative increase (0.12 ml / min / 0.79 ml / min) / (0.09 ml / min / 1.07 ml / min)
= 180.6%

Therefore, the relative increase in treated renal micturition was 180.6% compared to the control. The results show a greater reduction in urine production caused by stasis on the control side compared to the treatment side. Presenting the results as a relative percentage difference in urination regulates the difference in urination between the kidneys.

Glomerular clearance measurements for baseline, stasis, and treated areas for one of the animals are shown in FIG.
Gross examination and histological evaluation

Based on gross examination of the control kidney (right kidney) and the treated kidney (left kidney), it was determined that the control kidney had a uniform dark brown color, which was more stasis in the control kidney compared to the treated kidney. Corresponds to. Qualitative evaluation of enlarged section images also focused on increased stasis in the control kidney compared to the treated kidney. Specifically, as shown in Table 1, the treated kidney exhibited lower levels of stasis and tubular degeneration compared to the control kidney. The following qualitative scales were used to evaluate the slides obtained.

As shown in Table 1, the treated kidney (left kidney) exhibited only mild stasis and tubular degeneration. In contrast, the control kidney (right kidney) presented with moderate stasis and tubular degeneration. These results were obtained by analysis of the slides discussed below.

48A and 48B are low and high magnification light micrographs of the animal's left kidney (treated with negative pressure). Based on histological examination, low levels of intravascular stasis at the epithelial border were identified as indicated by the arrows. As shown in FIG. 48B, a single tubule with a glassy column (as identified by an asterisk) was identified.

48C and 48D are low and high resolution light micrographs of the control kidney (right kidney). Based on histological examination, moderate intravascular stasis at the epithelial border was identified as indicated by the arrow in FIG. 48C. As shown in FIG. 48D, several tubules with a glassy column were present in the tissue sample (as identified by the asterisk in the image). The presence of a substantial number of glassy cylinders is evidence of hypoxia.

The surface mapping analysis provided the following results. It was determined that the treated kidney had a fluid volume 1.5-fold higher in the Bowman's space and a 2-fold higher fluid volume in the tubular lumen. The increased fluid volume in the Bowman's space and tubular lumen corresponds to increased urination. In addition, it was determined that the treated kidney had a 5-fold smaller blood volume in the capillaries compared to the control kidney. The increased volume in the treated kidney is (1) a decrease in individual capillary size compared to the control kidney and (2) an increase in the number of capillaries without visible red blood cells in the treated kidney compared to the control kidney, ie. Appears as a result of less stasis indicators in the therapeutic organs.
summary

These results showed that the control kidney had more tubules with more stasis and intraluminal vitreous casts, representing protein-rich intraluminal material compared to the treated kidney. Is shown. Therefore, the treated kidney exhibits a lower degree of loss of renal function. Although not intended to be constrained by theory, it is believed that organ hypoxemia continues as severe stasis develops in the kidney. Hypoxemia interferes with oxidative phosphorylation (eg, ATP production) in the organ. Loss of ATP and / or decreased ATP production block active transport of protein and increase intraluminal protein content, which manifests as a glassy column. The number of renal tubules with intraluminal vitreous columns correlates with the degree of loss of renal function. Therefore, the reduced number of tubules in the treated left kidney is considered to be physiologically significant. Although not intended to be constrained by theory, these results prevent or prevent damage to the kidney by applying negative pressure to the ureteral catheter inserted into the renal pelvis to promote urination. It is thought to indicate that it can be blocked.
(Example 2)
Method

Four domestic pigs (A, B, C, D) were sedated and anesthetized. Vitals per pig were monitored throughout the experiment and cardiac output was measured at the end of each 30-minute phase of the study. A ureteral catheter, such as the ureteral catheter 112 shown in FIGS. 2A and 2B, was deployed within the renal pelvis region of each kidney in the pig. The catheter deployed was a 6 French catheter with an outer diameter of 2.0 ± 0.1 mm. The catheter is 54 ± 2 cm long and does not include the distal retention portion. The retention portion was 16 ± 2 mm long. As shown in catheter 112 in FIGS. 2A and 2B, the retention portion included two complete coils and one proximal half coil. The outer diameter of the complete coil shown by line D1 in FIGS. 2A and 2B was 18 ± 2 mm. The half coil diameter D2 was about 14 mm. The retaining portion of the deployed ureteral catheter contained six drainage openings as well as an additional opening at the distal end of the catheter tube. The diameter of each of the discharge openings was 0.83 ± 0.01 mm. The distance between the adjacent discharge openings 132, specifically the linear distance between the discharge openings when the coil was straightened, was 22.5 ± 2.5 mm.

The ureteral catheter was positioned to extend from the renal pelvis of the pig, through the bladder and urethra, to the fluid collection vessel outside each pig. Following the placement of the ureteral catheter, a pressure sensor for measuring IVC pressure was placed within the IVC at a location distal to the renal vein. Inflatable balloon catheters, specifically NuMED Inc. A PTS® percutaneous balloon catheter (30 mm diameter x 5 cm length) from Hopkinton, NY was dilated within the IVC at a location proximal to the renal vein. Thermally diluted catheters, specifically Edwards Lifescientes Corp. A Swan-Ganza heat-diluted pulmonary artery catheter manufactured by (Irvine, CA) was then placed in the pulmonary artery for the purpose of measuring cardiac output.

First, baseline micturition was measured over 30 minutes and blood and urine samples were collected for biochemical analysis. Following a 30 minute baseline period, the balloon catheter was inflated to increase the IVC pressure from a baseline pressure of 1-4 mmHg to an ascending stasis pressure of approximately 20 mmHg (+/- 5 mmHg). A stasis baseline was then collected with a corresponding blood and urine analysis over 30 minutes.

At the end of the period of stasis, elevated stasis IVC pressure was maintained and negative pressure diuretic treatment was provided to pigs A and C. Specifically, pigs (A, C) were treated by applying a negative pressure of -25 mmHg through a ureteral catheter using a pump. As in the examples discussed above, the pump was an AirCatet Vacuum Pump manufactured by Core-Parmer Instrument Company (model number EW-07530-85). The pump was connected in series with the regulator. The regulator is Airtrol Components Inc. It was V-800 Series Precision Vacuum Regulator-1 / 8NPT Ports (model number V-800-10-W / K). Pigs were observed over 120 minutes as treatment was provided. Blood and urine collections were performed every 30 minutes during the treatment period. Two of the pigs (B, D) were treated as stasis controls (eg, no negative pressure was applied to the renal pelvis through the ureteral catheter) and two pigs (B, D) were treated with negative pressure diuretics. It means that I did not receive it.

Following the collection of urination and creatinine clearance data over a 120 minute treatment period, the animals were sacrificed and the kidneys from each animal underwent a gross examination. Following macroscopic examination, tissue sections were obtained and examined, and magnified images of the sections were captured.
result

加えて、好中球ゼラチナーゼ結合性リポカリン（ＮＧＡＬ）値が、期間毎に取得された血清サンプルから測定され、腎臓傷害分子１（ＫＩＭ－１）値が、期間毎に取得された尿サンプルから測定された。取得された組織切片の精査から決定された定質的組織学的見解もまた、表２に含まれる。

Measurements collected during baseline, stasis, and treatment period are provided in Table 2. Specifically, urination, serum creatinine, and urinary creatinine measurements were taken on a period-by-period basis. These values allow the calculation of measured creatinine clearance as follows.

In addition, lipocalinase-binding lipocalin (NGAL) levels were measured from serum samples taken at each period and kidney injury molecule 1 (KIM-1) levels were measured from urine samples taken at each period. Was done. Qualitative histological views determined from scrutiny of the obtained tissue sections are also included in Table 2.

Animal A: The animal weighed 50.6 kg, had a baseline micturition volume of 3.01 ml / min, a baseline serum creatinine of 0.8 mg / dl, and was measured for CrCl of 261 ml / min. .. It should be noted that these measurements were non-characteristically higher compared to the other animals studied, in addition to serum creatinine. Stasis was associated with a 98% reduction in micturition volume (0.06 ml / min) and a> 99% reduction in CrCl (1.0 ml / min). Treatment with negative pressure applied through the ureteral catheter was associated with urination and CrCl of 17% and 12% of baseline values, respectively, and 9x and> 10x of stasis, respectively. Levels of NGAL varied throughout the experiment, ranging from 68% of baseline during stasis to 258% of baseline after 90 minutes of therapy. The final value was 130% of the baseline. KIM-1 levels were increased to 68, 52, and 63 times the baseline values over the last three collection periods, respectively, and the first two 30 minutes after the baseline assessment. It was 6 and 4 times the baseline over the time frame. The serum creatinine for 2 hours was 1.3 mg / dl. Histological examination revealed an overall stasis level of 2.4% as measured by blood volume in the capillary space. Histological examination also focused on intraluminal vitreous columns and some tubules with some degree of tubular epithelial degeneration and found to be consistent with cell damage.

Animal B: The animal weighed 50.2 kg, had a baseline micturition volume of 2.62 ml / min, and was measured for 172 ml / min (also higher than expected) of CrCl. Stasis was associated with an 80% reduction in micturition volume (0.5 ml / min) and an 83% reduction in CrCl (30 ml / min). At 50 minutes after becoming stasis (20 minutes after the stasis baseline period), the animals suffered a plunge in mean arterial pressure and respiratory rate, followed by tachycardia. An anesthesiologist administered a dose of phenylephrine (75 mg) to prevent cardiogenic shock. Phenylephrine is indicated for intravenous administration when blood pressure drops below safe levels during anesthesia. However, because the experiment was testing the effect of stasis on renal physiology, administration of phenylephrine made the rest of the experiment indistinguishable.

Animal C: The animal weighs 39.8 kg, has a baseline micturition volume of 0.47 ml / min, has a baseline serum creatinine of 3.2 mg / dl, and measures CrCl of 5.4 ml / min. Was done. Stasis was associated with a 75% reduction in urination (0.12 ml / min) and a 79% reduction in CrCl (1.6 ml / min). It was determined that the baseline NGAL level was> 5 times the upper limit of normal value (ULN). Treatment with negative pressure applied to the renal pelvis through a ureteral catheter was associated with normalization of urination (101% baseline) and 341% improvement in CrCl (18.2 ml / min). Levels of NGAL varied throughout the experiment, ranging from 84% of baseline during stasis to 47% -84% of baseline between 30 and 90 minutes. The final value was 115% of baseline. The first 30 of stasis before the KIM-1 level increased to 8.7 times, 6.7 times, 6.6 times, and 8 times the baseline value, respectively, over the remaining 30 minute time frame. Within minutes, it decreased by 40% from baseline. Serum creatinine levels at 2 hours were 3.1 mg / dl. Histological examination revealed an overall stasis level of 0.9% as measured by blood volume in the capillary space. It was noted that the renal tubules were histologically normal.

Animal D: The animal weighs 38.2 kg, has 0.98 ml / min baseline micturition, 1.0 mg / dl baseline serum creatinine, and is measured for 46.8 ml / min CrCl. rice field. Stasis was associated with a 75% reduction in micturition volume (0.24 ml / min) and a 65% reduction in CrCl (16.2 ml / min). Persistent stasis was associated with a 66% -91% reduction in urination and an 89% -71% reduction in CrCl. Levels of NGAL varied throughout the experiment, ranging from 127% baseline during stasis to a final value of 209% baseline. The first two 30-minute time frames after the baseline assessment, before the KIM-1 level increased to 190-fold, 219-fold, and 201-fold the baseline value over the last three 30-minute periods. It remained at 1 to 2 times the baseline over time. The 2-hour serum creatinine level was 1.7 mg / dl. Histological examination was observed in any of the treated animals with an average capillary size 2.44 times higher than that observed in the tissue sample for the treated animals (A, C). It was revealed that it was 2.33 times higher than the previous one. Histological assessment also focused on intraluminal vitreous casts and several tubules with tubular epithelial degeneration, showing substantial cell damage.
summary

Although not intended to be constrained by theory, the data collected may support the hypothesis that venous stasis has a physiologically significant effect on renal function. In particular, an increase in renal vein pressure was observed to reduce urination by 75% to 98% within seconds. The association between tubular and histologically injured elevations within the biomarker is consistent with the extent to which venous stasis occurs, both in terms of injury size and duration.

The data also show that by modifying the interstitial pressure, venous stasis supports the hypothesis that the filtration gradient within the medulla renal unit is reduced. It can be seen that the changes directly contribute to hypoxia and cytotoxicity within the medullary kidney unit. This model does not mimic the clinical status of AKI, but does provide insight into sustained mechanical injury.

The data also show that applying negative pressure to the renal pelvis through a ureteral catheter supports the hypothesis that urination in a venous stasis model can be increased. In particular, negative pressure treatment has been associated with increased micturition and creatinine clearance, which may be clinically significant. A physiologically significant decrease in medulla capillary volume and a slight increase in the biomarkers of tubular injury were also observed. Therefore, it can be seen that negative pressure therapy can directly reduce stasis by increasing urination volume and reducing interstitial pressure within the medullary renal unit. Although not intended to be constrained by theory, it can be concluded that negative pressure therapy reduces intrarenal hypoxia and its downstream effects in venous stasis-mediated AKI by reducing stasis.

Experimental results show that the degree of stasis supports the hypothesis that the degree of cell damage observed is associated with both the magnitude and duration of pressure. Specifically, an association between reduced micturition and the degree of histological damage was observed. For example, treated pig A with a 98% reduction in urination suffered more damage than treated pig C with a 75% reduction in urination. As would be expected, Control Pig D, which suffered a 75% reduction in urination without the benefits of therapy over two and a half hours, exhibited the most histological damage. These views are broadly consistent with human data demonstrating an increased risk of developing AKI with more venous stasis. For example, Legrand, M. et al. et al. , Observation between system hemodynamics and septic act kidney injury in clinically ill patients: a retrospective assistance. See Critical Care 17: R278-86, 2013.
(Example 3)
Method

Induction of negative pressure in the renal pelvis of domestic pigs using a ureteral catheter was performed for the purpose of assessing the effect of negative pressure therapy on blood dilution of blood. The purpose of these studies was to demonstrate whether the negative pressure delivered into the renal pelvis significantly increased micturition in a pig model of resuscitative fluid.

Two pigs were sedated and anesthetized using ketamine, midazolam, isoflurane, and propofol. One animal (# 6543) was treated with a ureteral catheter and negative pressure therapy as described herein. The other received a Foley-type bladder catheter and served as a control (# 6566). Following the placement of the ureteral catheter, the animals were transferred to the bed and monitored for 24 hours.

Volume overload was induced in both animals using a constant injection of saline (125 mL / hour) during the 24-hour follow-up. Urination volume was measured every 15 minutes for 24 hours. Blood and urine samples were collected every 4 hours. As shown in FIG. 21, the therapy pump 818 uses a pressure of -45 mmHg (+/- 2 mmHg) to induce negative pressure in the renal pelvis 820, 821 (shown in FIG. 21) of both kidneys. Was set to.
result

Both animals received 7 L of saline over a 24-hour period. The treated animal produced 4.22 L of urine, while the control produced 2.11 L. At the end of 24 hours, the control stored 4.94 L of the administered 7 L, while the treated animal stored 2.81 L of the administered 7 L. FIG. 26 illustrates changes in serum albumin. The treated animals showed a 6% drop in serum albumin concentration over 24 hours, while the control animals showed a 29% drop.
summary

Although not intended to be constrained by theory, the data collected believe support the hypothesis that volume overload induces clinically significant effects on renal function and, as a result, blood dilution. Be done. In particular, it has been observed that administration of large amounts of intravenous saline cannot be effectively eliminated, even by healthy kidneys. The resulting fluid accumulation leads to blood dilution. The data also show that applying negative pressure diuretic therapy to overloaded animals using a urinary catheter increases urination, improves net fluid balance, and reduces the effect of resuscitation infusion on the development of blood dilution. It seems to support the hypothesis that it can be made to urinate.

The aforementioned embodiments and embodiments of the present invention have been described with reference to various embodiments. Modifications and modifications will be recalled to those of skill in the art upon perusal and understanding of the aforementioned examples. Therefore, the aforementioned examples should not be construed as limiting this disclosure.

Claims (46)

A coated and / or impregnated urinary catheter or urethral stent device,
(A) Proximal and (b) Distal, said distal portion comprising a retention portion, said retention portion comprising at least one protected drain hole, port, or perforation. In response to the application of negative pressure through the catheter, the mucosal tissue is configured to establish an outer peripheral edge or protective surface area that prevents the mucosal tissue from occluding the at least one protected drainage hole, port, or perforation. Distal part and
At least one coating and / or at least one impregnation inside at least a portion of the protected surface area, wherein the at least one coating and / or at least one impregnation is lubricated. A device comprising at least one coating and / or at least one impregnation, comprising at least one of an agent, an antibacterial material, a pH buffer, or an anti-inflammatory material. The device of claim 1, wherein the at least one lubricant is configured to be lubricious in the presence of a fluid. The device of claim 1, wherein the at least one lubricant comprises a hydrophilic material. The device of claim 3, wherein the hydrophilic material comprises a gel. The at least one lubricant includes polyethylene glycol, polyvinylpyrrolidone, polytetrafluoroethylene, polyvinyl alcohol, polyacrylamide, polymethacrylic acid, acrylic polymers or copolymers thereof, polyelectrolytes, hydrogels containing polyacrylic acid, and / or. The device of claim 1, comprising at least one of the disulfide crosslinks (poly (oligo (ethylene oxide) monomethyl ether methacrylate). The device of claim 1, wherein the at least one lubricant comprises at least one of polytetrafluoroethylene, siloxane, silicone, or polysiloxane. The device of claim 1, wherein the at least one coating and / or impregnation comprises at least one outermost layer comprising at least one lubricant. The at least one coating and / or impregnation further comprises at least one sublayer positioned between the protective surface area of the device and the at least one outermost layer, wherein the at least one sublayer is at least one. The device of claim 7, comprising an antibacterial material. The at least one lubricant dissipates into the surrounding fluid or tissue over time, thereby exposing the at least one sublayer to the fluid and / or tissue surrounding the deployed device. Item 8. The device according to item 8. The device of claim 9, wherein the at least one lubricant dissipates over a period of 1 to 10 days following insertion of the device into the patient's urinary tract. 9. Claim 9 the outermost layer is configured such that at least one antibacterial material in the at least one sublayer is configured to be released into a surrounding fluid or tissue in response to the dissipation of at least one lubricant in the outermost layer. Device. The device of claim 8, wherein the at least one antibacterial material of the at least one sublayer is configured for sustained release into the surrounding fluid or tissue over a period of about 1 day to about 1 year. The at least one sublayer is a first sublayer applied to the protective surface area of the device, the first sublayer being the first sublayer comprising a pH buffering material and the first sublayer. 8. A second sublayer that covers at least a portion of the sublayer, wherein the second sublayer comprises a second sublayer comprising the at least one antibacterial material. The device described. The device of claim 1, wherein the at least one antibacterial material comprises at least one of a bactericidal material, an antiviral material, an antibacterial material, an antifungal material, or an antibiotic material. The at least one antibacterial material is among chlorhexidine, silver ion, nitrogen oxide, bacteriophage, sirolimus, heparin, phosphorylcholine, silicon dioxide, diamond-like carbon, caspopofangin, chitosan, organosilane, sulfonamide, or antibacterial peptide. The device of claim 1, comprising at least one. 15. The device of claim 14, wherein the at least one antibiotic material comprises at least one of amdinocillin, levofloxacin, penicillin, tetracycline, sparfloxacin, or vancomycin. The device of claim 1, wherein the at least one antibacterial material comprises at least one antibacterial material and at least one antibiotic material. The device of claim 1, wherein the at least one coating and / or impregnation comprises at least one lubricant and at least one antibacterial material. 18. The device of claim 18, wherein the at least one lubricant is present in the outermost layer of the coating. The device of claim 1, wherein the at least one antibacterial material resides within a sublayer of the coating located between the protective surface area of the device and the outermost layer of the coating. The at least one coating is
An innermost layer located above a portion of the protective surface area of the device, wherein the innermost layer comprises an innermost layer comprising at least one hydrophilic material.
A first sublayer containing the at least one antibacterial material, located above at least a portion of the innermost layer.
With the at least one second sublayer containing the at least one antibiotic material, located on the at least one first sublayer.
A third sublayer located on the second sublayer, wherein the third sublayer comprises a third sublayer comprising the at least one antibacterial material.
The device of claim 1, wherein the outermost layer is located on the third sublayer, wherein the outermost layer comprises an outermost layer comprising the at least one hydrophilic material. The sublayer containing the antibacterial material is configured for sustained release of the at least one antibacterial material into the body fluid or tissue surrounding the device for a period of at least 24 hours. The at least one second sublayer containing the antibiotic material is configured to release the at least one antibiotic material into the fluid or tissue surrounding the device for a period of less than 24 hours. The device according to claim 21. The device of claim 1, wherein the at least one pH buffering agent comprises at least one of sodium citrate, sodium acetate, or sodium bicarbonate. The device of claim 1, wherein the at least one anti-inflammatory material comprises at least one of dexamethasone, heparin, or alpha-melanocyte stimulating hormone (α-MSH). The at least one anti-inflammatory material is a polyethylene glycol-containing polymer, poly (2-hydroxyethylmethacrylate), poly (N-isopropylacrylamide), poly (acrylamide), phosphorylcholine polymer, mannitol, oligomaltose, or taurine group. The device of claim 1, comprising at least one of. The device of claim 1, wherein the device comprises at least one coating on at least a portion of the protected surface area. The device of claim 1, wherein the device comprises at least one impregnation within at least a portion of the protected surface area. The device according to claim 1, wherein the device is a ureteral catheter. The device according to claim 1, wherein the device is a bladder catheter. The device of claim 1, wherein the proximal end of the proximal portion of the device is configured to be directly or indirectly connected to a pump for applying negative pressure to the device. The device may be copper, silver, gold, nickel-titanium alloy, stainless steel, titanium, polyurethane, polyvinyl chloride, polytetrafluoroethylene (PTFE), latex, silicon coated latex, silicone, polyglycolide or poly (glycol). A claim comprising at least one of acid) (PGA), polylactic acid (PLA), poly (lactic acid-co-glycolic acid), polyhydroxyalkanoic acid, polycaprolactone, and / or poly (propylene fumarate). The device according to 1. The at least one protected drain hole, port, or perforation is placed on the protected or inner surface area of the retention portion, and the outer peripheral edge or protection surface area of the retention portion of the catheter supports the mucosal tissue. And thereby configured to prevent obstruction of one or more of the protected drain holes, ports, or perforations in response to the application of negative pressure through the ureteral catheter. Item 1. The device according to Item 1. The retention portion comprises one or more spiral coils, each coil having an outward facing side and an inward facing side, the outer peripheral edge or protective surface area of the one or more. 1. An outward facing side of the spiral coil, wherein the at least one protected drain hole, port, or perforation is located on the inward facing side of the one or more spiral coils. The device described in. The device of claim 1, wherein the retention portion is configured to extend to a deployment position where the diameter of the retention portion exceeds the diameter of the drainage lumen portion. The number of the drain holes, ports, or perforations directed to the distal end of the retention portion is greater than the number of the drain holes, ports, or perforations directed to the proximal end of the retention portion, claim 1. Device. The size of one or more of the drain holes, ports, or perforations towards the distal end of the retention portion is of the drain holes, ports, or perforations towards the proximal end of the retention portion. The device of claim 1, which exceeds the size of one or more. The total area of the drain holes, ports, or perforations towards the distal end of the retention portion exceeds the total area of the drain holes, ports, or perforations towards the proximal end of the retention portion, claim 1. The device described in. The device of claim 1, wherein the side wall of the proximal portion of the device has essentially no or no drainage opening. A coated urinary catheter or urethral stent device,
(A) Proximal and (b) Distal, said distal portion comprising a retention portion, said retention portion comprising at least one protected drain hole, port, or perforation. In response to the application of negative pressure through the catheter, the mucosal tissue is configured to establish an outer peripheral edge or protective surface area that prevents the mucosal tissue from occluding the at least one protected drainage hole, port, or perforation. Distal part and
A device comprising at least one coating on at least a portion of the protected surface area, wherein the coating comprises a coating and a pH buffering material. 39. The device of claim 39, wherein the coating comprises at least one outermost layer comprising the lubricant. 39. The device of claim 39, wherein the coating further comprises at least one sublayer positioned between the catheter or stent and the outermost layer, wherein the at least one sublayer comprises the pH buffering material. A method of manufacturing a coated and / or impregnated catheter or stent device, said method.
The application of at least one sublayer of the coating to at least a portion of the catheter or stent, wherein the at least one sublayer comprises at least one of an antibacterial material and a pH buffering material.
A method comprising applying at least one outermost layer of the coating over at least a portion of the at least one sublayer, wherein the at least one outermost layer comprises a lubricant. The catheter or stent is configured to be deployed in the patient's urinary tract, and in the deployed position, the catheter or stent comprises a protected surface area and a protected surface area, and the coating is at least the catheter or 42. The method of claim 42, which applies to the protective surface area of the stent. 42. The method of claim 42, wherein the antibacterial material comprises at least one of an antibacterial material and an antibiotic material. Forming at least one opening, hole, space, and / or microchannel on the distal portion of the catheter or stent.
42. The method of claim 42, further comprising forming a deployable retention portion on the distal portion of the catheter or stent. Applying the at least one sublayer comprises applying the first sublayer containing the pH buffering material to reduce the coat of urinary crystals on the catheter or stent and the first sublayer. 42. The method of claim 42, comprising applying a second sublayer comprising said antibacterial material that covers at least a portion of the sublayer.

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