WO2011032087A2

WO2011032087A2 - Swellable polymeric device for dietary regulation

Info

Publication number: WO2011032087A2
Application number: PCT/US2010/048626
Authority: WO
Inventors: Ann Prewett
Original assignee: Replication Medical Inc.
Priority date: 2009-09-11
Filing date: 2010-09-13
Publication date: 2011-03-17
Also published as: WO2011032087A3

Abstract

A stomach implant is provided to reduce the volume of the stomach for treating obesity and for dietary regulation. The implant is made from a hydrogel capable of reducing its volume when exposed to stomach acids. Volume reduction assures free passage of digested foods through the stomach and into duodenum without the implant obstructing any of the stomach openings. In embodiments, the implant is made of a hydrogel and can be dehydrated to minimize its volume prior to insertion.

Description

Swellable Polymeric Device for Dietary Regulation

Cross -Reference Data

This application claims a priority benefit from the provisional US Application No. 61/241,727 with the same title filed 11 September 2009, incorporated herein by reference in its entirety.

Background

[001] Technical Field - the invention relates to treatment of obesity by reducing the volume of the stomach.

Description of Related Art

[002] Obesity is a growing problem in developed countries. High caloric diets and fatty foods have led to weight and health problems now commonly treated with surgery. In particular, bariatric surgery is a treatment for morbid obesity that involves alteration of a patient's digestive tract to encourage weight loss and to help maintain normal weight. Examples include gastric bypass, stomach stapling and banding which are highly invasive and have been associated with complications. For example, gastric bypass and/or intestinal bypass have been associated with malnutrition, uncontrollable diarrhea, dehydration and electrolyte imbalance. Stomach stapling involves stapling two walls of the stomach together while leaving a small gap. Food is held up in the segment of stomach above the staple line causing the sensation of fullness. The food then empties slowly through the gap (stoma) into the stomach below the staple line where digestion takes place normally. Unfortunately, the muscular stomach wall has a tendency to stretch and the stoma enlarges, thus allowing consumption of larger and larger amounts of food. In addition, staple line failure is known to occur. Gastric banding involves placing a constricting ring completely around the top end (fundus) of the stomach, thus creating an hourglass configuration. The ring is placed near the upper end of the stomach, just below the junction of stomach and esophagus. If strict compliance with dietary limitations are not followed, the upper portion of the "hourglass" expands, thus pushing the band downward and potentially into the intestinal region. Invasive surgery is required to reposition or remove the band. Another technique involves disposing an inflated bag within a patient's stomach to decrease the effective volume of the stomach. See, e.g., US Pat. No. 4,416,267. Endoscopic procedures that have been used to assist weight loss have been primarily focused on the placement of a balloon or other space occupying device in the patient's stomach to fill portions of the stomach and provide the patient with the feeling of fullness, thereby reducing food intake. To accomplish these procedures, an endoscope is utilized to guide the balloon through the patient's mouth and down the esophagus to the stomach. However, free floating balloons may block the pyloric sphincter or the cardiac orifice.

Summary of the Invention

[003] The present invention describes a swellable pH- sensitive indwelling stomach implant adapted for reducing the stomach volume for the purposes of dietary regulation. The implant is configured to transition from an expanded state to a reduced volume state when exposed to a stomach acid. The purpose for reducing volume when exposed to acid is to prevent blocking of the stomach or a pyloric orifice when food is present in the stomach.

Brief Description of the Drawings

[004] Subject matter is particularly pointed out and distinctly claimed in the concluding portion of the specification. The foregoing and other features of the present disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which:

Figure 1 shows an implant of the invention in which multiple elements are connected together with flexible ties to form a chain;

Figure 2 shows schematically an implant of the invention including internal air pockets configured to alter the density of the implant to make it buoyant; and

Fi ure 3 shows an implant of the invention with multiple voids and openings configured to allow stomach content to pass through. Detailed description of the preferred embodiments of the invention

[005] The following description sets forth various examples along with specific details to provide a thorough understanding of claimed subject matter. It will be understood by those skilled in the art, however, that claimed subject matter may be practiced without one or more of the specific details disclosed herein. Further, in some circumstances, well-known methods, procedures, systems, components and/or circuits have not been described in detail in order to avoid unnecessarily obscuring claimed subject matter. In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented here. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the figures, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this disclosure.

[006] An indwelling fluid-absorbing swellable pH-sensitive polymeric stomach implant is used to add permanent or semi-permanent physical bulk to the stomach in order to reduce stomach volume. The product can be placed into the stomach without surgery using minimally invasive techniques. In embodiments, laparoscopic or endoscopic techniques are utilized. For example, an endoscope or a cannula may be passed through the throat into the esophagus and advanced into the stomach cavity. The endoscope may be covered with a thin polyurethane or other suitable polymeric deployment sheath which will enable removal of the endoscope leaving the sheath resident in the stomach. The implant may be advanced through the sheath by any suitable mans. Once in the abdominal cavity, positioning can be verified by direct vision using an endoscope or by other visualization techniques such as X-Ray, ultrasound, etc. In embodiments, the implant may incorporate a contrast material to aid in such visualization. Also in embodiments the implant may contain a mesh or other reinforcing or anchoring elements configured for attachment of the implant to the stomach wall in order to prevent dislodgement or migration of the device. The mesh allows for fixation of the implant through the endoscope to the wall of the stomach such as using suturing or stapling technique. Alternative anchoring elements may include a fabric strip made for example from biocompatible polyethylene or Dacron material. Anchoring the implant to the wall of the stomach may be helpful in preventing the implant from being thrown out of the stomach if the patient experiences nausea and vomiting.

[007] In embodiments, in order to prevent the implant from blocking the stomach openings, it can be made buoyant i.e. having a similar or lower density to that of the stomach content. This may allow the implant to retain buoyancy in the presence of food and digestive stomach fluids. Buoyancy may be imparted by, e.g., infiltrating the implant with suitable voids such as for example closed cells containing air as shown in Fig. 2.

[008] The implant may be characterized by being in one of three characteristic states: a collapsed state, an expanded state, and a reduced volume state. In its collapsed state, the implant has a smallest volume of all three states and is suitable for insertion. In embodiments, the implant may be placed in its collapsed state by dehydration. The expanded state is characterized by the implant absorbing fluid and expanding. The volume of the implant is the largest in the expanded state.

[009] In embodiments, the pH- sensitive nature of the polymer causes the implant to constrict in size with exposure to decreasing pH and enter its reduced volume state. Thus, when food is consumed, digestive processes result in production of stomach acid, lowering the pH of the stomach contents, whereby causing the polymer to shrink along with the implant as a whole so as to prevent blockage of the duodenum opening and allowing passage of digested food through the pyloric orifice. In embodiments, the fluid-absorbing polymer is contained in a mesh bag that allows fluid to pass across the bag. The polymer must be highly resistant to pH extremes and be hydrolytically stable under these conditions. In the event smaller morsels or beads are employed, a mesh bag is necessary for retention.

[0010] In embodiments, the fluid-absorbing sponge polymer is dehydrated, e.g., to a xerogel, which markedly reduces the volume of the implant and places it in the collapsed state. The dehydrated implant is then administered to the stomach via a tube or other suitable means where it imbibes fluid and expands. The volume of dehydrated implants may range, e.g., from about 0.5 cubic centimeters to 3 cubic centimeters. Expansion or swelling may range from about three fold to about twenty fold. Expansion of the implant causes a reduction in the empty volume of the stomach. The reduced volume of the stomach, as compared to the native volume, constrains the amount of food that a patient consumes by providing a feeling of satiety after only a small amount of food has been consumed. Furthermore, the reduced cross- sectional area of the stomach reduces the rate in which food passes through the GI lumen. This increases the residence time of the food within the upper portion of the GI lumen, thereby enhancing the feeling of satiety. [0011] As mentioned above, in embodiments, pH-responsive hydrogels can shrink in response to lowering pH, e.g., from about two to five times a reduction in volume. The implant may also be administered orally, in admixture with the food or drinking water, or by separate oral administration, or by gavage. They can also be administered by intragastric intubation, or directly into the stomach or small intestine when appropriate.

[0012] The polymers used in the invention are indigestible and pharmacologically- acceptable. The term "indigestible" is used herein to indicate that the polymers are not absorbed from the gastrointestinal tract, nor are they degraded or metabolized to an appreciable extent in the gastrointestinal tract to produce components which are absorbed. Thus, the polymers are also insoluble in the gastrointestinal liquids. They are insoluble in both the gastric fluid and bile produced by the animal. They are also insoluble in the ingesta, which can include both water and water-miscible liquids such as glycerol as well as water immiscible liquids such as liquid dietary fats, fatty acids and edible oils, under the gastrointestinal tract conditions. The polymers are capable of remaining essentially undissolved throughout their residence in the gastrointestinal tract, and are not absorbed through the stomach or intestinal wall either as a solid or as a solution in the aqueous or fatty liquids which are absorbed in the digestive process. It is understood that the polymers are thus not degraded by acidic gastric fluid, or by digestive enzymes. They are not soluble in either gastric fluid or in the bile, nor are they solubilized by the surfactant action of the bile salts.

[0013] Preferred fluid-absorbing polymers are hydrogels that contain carboxyl groups which cause the pH-sensitive response of volume reduction. Water-soluble polymers with charged side groups may be crosslinked by reacting the polymer with an aqueous solution containing ions of the opposite charge, either cations if the polymer has acidic side groups or anions if the polymer has basic side groups. Examples of cations for cross-linking of the polymers with acidic side groups to form a hydrogel are monovalent cations such as sodium, divalent cations such as calcium, and multivalent cations such as copper, calcium, aluminum, magnesium, strontium, barium, and tin, and di-, tri- or tetra-functional organic cations such as alkylammonium salts. Aqueous solutions of the salts of these cations are added to the polymers to form soft, highly swollen hydrogels and membranes. The higher the concentration of cation, or the higher the valence, the greater the degree of cross-linking of the polymer. Additionally, the polymers may be crosslinked enzymatically, e.g., fibrin with thrombin. The polymers can be covalently crosslinked as well through the addition of ethylene diamine, NBS or a host of crosslinking agents routinely to react with amino, nitrile, urethane and carboxylic functional groups found on the polymer chain.

[0014] Suitable ionically crosslinkable groups include phenols, amines, imines, amides, carboxylic acids, sulfonic acids and phosphate groups. Negatively charged groups, such as carboxylate, sulfonate and phosphate ions, can be crosslinked with cations such as calcium ions. The crosslinking of alginate with calcium ions is an example of this type of ionic crosslinking. Positively charged groups, such as ammonium ions, can be crosslinked with negatively charged ions such as carboxylate, sulfonate and phosphate ions. Preferably, the negatively charged ions contain more than one carboxylate, sulfonate or phosphate group.

[0015] Anions for cross-linking of the polymers to form a hydrogel are monovalent, divalent or trivalent anions such as low molecular weight dicarboxylic acids, for example, terepthalic acid, sulfate ions and carbonate ions. Aqueous solutions of the salts of these anions are added to the polymers to form soft, highly swollen hydrogels, as described with respect to cations.

[0016] A variety of polycations can be used to complex and thereby stabilize the polymer hydrogel into a semi-permeable surface. Examples of materials that can be used include polymers having basic reactive groups such as amine or imine groups, having a preferred molecular weight between 3,000 and 100,000, such as polyethylenimine and polylysine. These are commercially available. One polycation is poly(L-lysine); examples of synthetic polyamines are: polyethyleneimine, poly(vinylamine), and poly(allyl amine). There are also natural polycations such as the polysaccharide, chitosan.

[0017] In embodiments, the implant is made of a hydrogel. Prior to coagulation, the liquid form of a suitable hydrogel is used to form the expanded configuration as it would be in the hydrated state. The hydrogel is then coagulated to form the implant in an expanded configuration. The implant is then dehydrated to a xerogel state which reduces the volume of the implant to the reduced configuration. Many hydrogel polymers behave in a similar manner, which is to say they can be deformed, frozen into a deformed shape and they can maintain that shape indefinitely or until, e.g., a temperature change causes the polymer to "relax" into the shape originally held prior to freezing. This property can be referred to as shape memory or frozen deformation by those skilled in the art.

[0018] The temperature at which frozen deformation occurs is referred to as the glass transition temperature or T_g. At T_g several polymer properties such as density, entropy and elasticity may sharply change. Many polymers can be mixed with agents that can have a drastic effect on a polymer T_g. Polymers which absorb fluid are of particular interest and water is the preferred T_g altering agent. Hydrogels which contain less than about five percent water may be considered dehydrated or xerogels. The T_g of a xerogel will change as it absorbs fluids containing water. Once the T_g becomes lower than ambient the now partially hydrated hydrogel becomes pliant and may be elastically deformed. If the polymer is held in a state of elastic deformation while the T_g is raised above ambient the polymer will maintain the deformed state indefinitely. This can be accomplished by either lowering the ambient temperature (freezing) or by returning the polymer to its xerogel state thus raising the T_g.

[0019] A preferred polymer configuration includes two polymer phases of different hydrophilicity, the less hydrophilic phase having higher content of hydrophobic groups and more hydrophilic phase having higher content of hydrophilic groups. The less hydrophilic phase is preferably crystalline and more hydrophilic phase is preferably amorphous, as can be established from X-ray diffraction.

[0020] Advantageous hydrophobic groups are pendant nitrile substituents in 1,3 positions on a polymethylene backbone, such as poly(acrylonitrile) or poly(methacrylonitrile). The hydrophilic phase may preferably contain a high concentration of ionic groups. Preferred hydrophilic groups are derivatives of acrylic acid and/or methacrylic acid including salts, acrylamidine, N-substituted acrylamidine, acrylamide and N-substituted acryl amide, as well as various combinations thereof. A particularly preferred combination contains approximately two thirds acrylic acid and its salts (on molar basis), the rest being a combination of plain and N-substituted acrylamides and acrylamidines.

[0021] At least one polymeric component is preferably a multiblock copolymer with alternating sequences of hydrophilic and hydrophobic groups. Such sequences are usually capable of separating into two polymer phases and form strong physically crosslinked hydrogels. Such multiblock copolymers can be, for example, products of hydrolysis or aminolysis of polyacrylonitrile or polymethacrylonitrile and copolymers thereof. For convenience, polymers and copolymers having at least about 80 molar % of acrylonitrile and/or methacrylonitrile units in their composition may be referred to as "PAN". Hydrolysis and aminolysis of PAN and products thereof are described, for example, in U.S. Pat. Nos. 4,107,121; 4,331,783; 4,337,327; 4,369,294; 4,370,451; 4,379,874; 4,420,589; 4,943,618, and 5,252,692, each being incorporated herein by reference in their respective entireties.

[0022] A preferred fluid absorbing polymer for the implant is a synthetic composite of a cellular (or domain) type with continuous phase formed by a hydrophobic polymer or a hydrophilic polymer with low to medium water content forming a "closed cell" spongy structure that provides a composite with good strength and shape stability. Examples of suitable polymers are polyurethanes, polyureas, PAN, and highly crystalline multiblock acrylic and methacrylic copolymers. The polymer should be sufficiently permeable to water. More preferably, the continuous phase is formed by a strong hydrophilic polymer with sufficient permeability for water but impermeable to high-molecular solutes. Examples of such polymers are highly crystalline hydrogels based on segmented polyurethanes, polyvinylalcohol or multiblock acrylonitrile copolymers with derivatives of acrylic acid. Typically, suitable polymers for the continuous phase in cellular composites have a water content in fully hydrated state between about 60% by weight and about 90% by weight, preferably between about 70% and about 85% by weight.

[0023] The second component of the fluid-absorbing polymer may be a highly hydrophilic polymer of high enough molecular weight to prevent permeation of the hydrophilic polymer through the continuous phase. This component is contained inside the matrix of the continuous phase. The entrapped hydrophilic polymers (the so-called "soft block") may be high-molecular weight water-soluble polymers, associative water-soluble polymers or highly swellable hydrogels containing, in a fully hydrated state, an amount of hydration which is preferably at least about 5% greater than the hydrophobic component. For example, the second component hydrated to at least about 65% when the first component is hydrated to about 60%. In embodiments, e.g., from the second component could be fully hydrated at from about 95% of water and up to about 99.8% of water. Such hydrogels are very weak mechanically. However, it may not matter in composites where such polymers' role is generation of osmotic pressure rather than load-bearing, with e.g., compression strength in full hydration in the range of about 0.01 MN/m or lower.

[0024] A system with closed cells (or domains) containing highly swellable or water-soluble polymers can form composites with very high swelling pressure as needed for the implant anchoring function. Examples of suitable hydrophilic polymers are high-molecular weight polyacrylamide, polyacrylic acid, polyvinylpyrrolidone, polyethyleneoxide, copolymers of ethyleneoxide and propyleneoxide or hyaluronic acid; covalently crosslinked hydrogels such as hydrophilic esters or amides of polyacrylic or polymethacrylic acids; and physically crosslinked hydrogels, such as hydrolyzates or aminolysates of PAN.

[0025] Particularly suitable are associative water-soluble polymers capable of forming very highly viscous solutions or even soft physical gels. Preferred are associative polymers containing negatively charged groups, such as carboxylates, sulpho-groups, phosphate groups or sulfate groups. Particularly preferred are associative polymers formed by hydrolysis and/or aminolysis of PAN to high but finite conversions that leave a certain number of nitrile groups (typically, between about 5 and 25 molar %) unreacted. [0026] Preferred fluid-absorbing polymer composites have both a continuous phase and a dispersed phase formed by different products of hydrolysis or aminolysis of PAN. In this case, both components are compatible and their hydrophobic blocks can participate in the same crystalline domains. This improves anchorage of the more hydrophilic component and prevents its extraction or disassociation. The size of more hydrophilic domains may vary widely, from nanometers to millimeters, preferably from tens of nanometers to microns.

[0027] The ratio between the continuous and discrete phases (i.e., between more hydrophobic and more hydrophilic components) may vary from about 1:2 to about 1:100 on a dry weight basis, and a preferred ratio ranges from about 1:5 to about 1:20. Examples of compositions and implants are described in US Pat. Nos. 6,264,695 and 6,726,721, both of which are incorporated herein by reference in their entireties. A preferred method of making the fluid absorbing polymer composite is described in US Pat. No. 6,232,406, herein incorporated by reference in its entirety.

[0028] Examples of particularly suitable hydrogel forming copolymers are prepared by a partial alkaline hydrolysis of polyacrylonitrile ("HPAN") in the presence of sodium thiocyanate (NaSCN). The resulting hydrolysis product is a multi-block acrylic copolymer, containing alternating hydrophilic and hydrophobic blocks. Hydrophilic blocks contain acrylic acid, acrylamidine, and acrylamide. In embodiments, for example, a PAN hydrolysate polymer (referred to herein HPAN I) (46+1% conversion of hydrolysis) having the following composition: acrylonitrile units -53-55%, acrylic acid units -22-24%, acrylamide units -17-19%, acrylamidine units -4-6%, as determined by 13 C NMR, is dissolved in a suitable solvent such as a -55% solution of sodium thiocyanate in water to form a viscous solution. The viscous solution is poured into an extruder or porous mold having, e.g., a cavity defining the dimensions of the rod. The solution can then be solvent cast, e.g., by solvent exchange (e.g., water for NaSCN). The pores should be sufficiently small as to not permit the polymer to diffuse or leak out of the mold. In another form, the hydrogel used to make the implant is obtained by reacting an aquagel of PAN, formed by dissolving the polymer in an aqueous solvating solution such as high concentration of sodium thiocyanate. The resulted solution of PAN is thereupon coagulated through addition of a suitable aqueous solvent or water miscible solvent. The coagulum is further reacted in a hydrolyzing basic or acidic medium. The PAN aquagel can then be processed as a thermoplastic and molded to obtain the desired shape. These methods are described in US Patent No. 4,943,618. [0029] A more rigid fluid absorbing polymer may be another PAN hydrosylate polymer, referred to herein as HP AN II (28+1% conversion of hydrolysis), having the following composition: acrylonitrile units -71-73%, acrylic acid units -13-15%, acrylamide units -10- 12%, acrylamidine units -2-4%, as determined by ¹³C NMR, disolved in -55% NaSCN which can be solvent cast, washed, dried and cut to a suitable shape. HP AN hydrogel is preferred for this application. It is inert, biocompatible and very stable to other acidic hydrolytic conditions. However, other suitable hydrogel polymers may be utilized as well for this application.

[0030] The shape of the implant when in its expanded state may be generally round or oval. More than one element may be connected into a chain using flexible ties such as sutures. This configuration is shown in Fig. 1 and has an advantage of allowing to use flexible ties for attaching the implant to the stomach wall as well as making it easy to adjust the total volume of the implant by cutting one or more of the implant elements off prior to implantation into a patient.

[0031] In embodiments, to facilitate passage of digested food around the implant of the invention, the shape of the implant may include one or more protrusions. Such protrusions are envisioned to extend from the main body of the implant and are configured to prevent the body of the implant from blocking various openings of the stomach and surrounding organs of the digestive system. In embodiments, between two and 10 protrusions may be formed on the main body of the implant. Each protrusion may be about ¼ to ¾ of an inch high and contain a free end which in itself is formed to be rounded so as to prevent trauma or irritation to the stomach wall tissues.

[0032] In embodiments, the shape of the implant may be generally round or oval and include internal openings or passages therethrough. At least one such internal passage is envisioned. In embodiments, up to one hundred such internal passages may be formed inside the implant. The openings of such internal passages are located throughout the outer surface of the implant (as shown in Fig. 3) so as to provide for unrestricted flow of digested food and other stomach content therethrough even in case the implant is located up against the entrance or exit from the stomach. The size or diameter of such internal passage has to satisfy the requirement of being able to pass through the digested food with minimum flow restriction.

[0033] In embodiments, the shape of the implant may allow for customization at the time of implantation. The implant may for example contain a number of breakaway sections which can be snapped off by the practitioner before implantation so as to adjust the overall volume of the implant based on specific needs of each individual patient. Between one and 5 of such breakaway sections may be provided. They may be made in the form of protrusions as described above. Reducing the number of protrusions will allows adjusting the volume of the implant while remaining protrusions will still prevent blocking of the stomach openings by the implant of the invention.

[0034] In embodiments, the breakaway sections of the implant may be shaped to be grasped by an endoscope so as to provide for the opportunity to reduce the volume of the implant at some point of time after the initial implantation. This may be desirable for gradual weaning of the patient from relying on the implant of the invention to reduce obesity. In this case, a portion of the implant is envisioned to be removed by an endoscope once or over a number of occasions after initial implantation of the device therefore providing for gradual decrease in the implant volume over time.

[0035] The size of the implant may be selected to prevent its ejection in case of forceful vomiting by the patient. As the normal diameter of the esophagus generally varies between 2 and 3 cm, the smallest size of the implant when expanded is selected preferably to exceed the esophageal diameter.

[0036] In embodiments, the implant of the invention may be made using a radiopaque hydrogel material or contain radiopaque inclusions so as to facilitate it imaging using X-Ray or fluoroscopy techniques.

[0037] The implant may optionally include an interiorly-embedded reinforcement member. The reinforcement member occupies at least a portion of the interior of the implant. The reinforcement member can have a planar configuration or it can be one or more rods or beams of relatively rigid material which can extend for a portion of or the entire length of the implant or it can consist of two or more members. In embodiments, the reinforcement member extends from the interior of the implant to the exterior, thereby extending beyond the main body of implant. In embodiments, the reinforcement member may be made of a series of individual fibers or ribbons which are arranged in parallel or non-parallel fashion and extend throughout the implant. In embodiments, the reinforcement member can be a fabric or mesh. Woven, non-woven, knitted or braided configurations are suitable. A reinforcement member may be made of a polymeric material which is natural, e.g., cotton, or synthetic, e.g., polyester, polyamide, or other materials such as metal fiber, fiber glass, and carbon fiber. Methods of making shaped objects from these materials and others are well-known to those skilled in the art. Foils or ribbons herein may also be made of metal or polymeric material and are well-known. Thus, the reinforcement member may be constructed from relatively durable materials including, but not limited to, metal foil, plastic foil, metal fibers, polymeric fibers of materials such as polycarbonate, polyethylene, polypropylene, polystyrene, polyethylene terephthalate, polyamide, polyurethane, polyurea, polysulfone, polyvinyl chloride, acrylic and methacrylic polymers, expanded polytetrafluoroethylene (Goretex®), ethylene tetrafluoroethylene, graphite, etc. These materials can be used either alone, or in a composite form in combination with elastomers or hydro gels. Alternatively, the reinforcement member may be exteriorly disposed, e.g., a jacket which surrounds all or part of the implant. The reinforcement member is designed to provide support for the implant and to buttress any fastener which may be used to help maintain the implant in place in the stomach. Suitable fasteners include, but are not limited to sutures, screws, staples, barbs and the like. The reinforcement member may be pre-loaded with one or more fasteners or not, e.g., in the situation where a fastener is applied by the surgeon during implantation.

[0038] A reinforced implant herein may be manufactured by providing a reinforcement member of desired configuration and placing it in a mold. A pH-sensitive fluid-absorbing liquid polymer is added to the mold and surrounds the reinforcement member. In embodiments, a gap, e.g., about l-3mm or more, is left between one or more sides of the reinforcement member and the walls of the mold. Fluid-absorbing liquid polymer is allowed to fill the gap between the mold and the reinforcement member. When the fluid absorbing polymer is cured or fixed, e.g., by solvent casting, ionic gelation, photo-polymerization and the like, it solidifies and encapsulates the reinforcement member. In the case of solvent casting, the mold may be made of material which is impermeable to the fluid absorbing polymer but permeable to water. The mold is placed in a water bath to extract the solvent (e.g., sodium thiocyanate) which causes the polymer to coagulate. The mold may then be opened and any remaining solvent in the implant is extracted. If it is desired to leave one or more sides of the implant open to the reinforcement member, then the desired side(s) of the reinforcement member is placed up against the wall of the mold to prevent formation of a gap for the liquid fluid-absorbing polymer to fill.

[0039] In one embodiment, the fluid-absorbing polymer is made to achieve a strong physical bond to the reinforcement member by incorporating an initial treatment of the reinforcement member with a relatively hydrophobic fluid- absorbing polymer to create an encapsulating layer of the relatively hydrophobic fluid-absorbing polymer. For example, a hydrogel such as HP AN II is applied to the reinforcement member as a 10% solution by weight in a solvent (sodium thiocyanate 55% by weight in water) and then coagulated onto the reinforcement member by solvent exchange with an aqueous solution such as water. As the polymer coagulates, it shrinks volumetrically around the reinforcement member, causing a tight physical bond to the reinforcement member. If desired, the treated reinforcement member is placed in a mold and a relatively more hydrophilic fluid-absorbing polymer in the liquid state is added to create a cohesive continuous polymer matrix which surrounds the reinforcement member. For example, a 10% by weight HP AN I in a 55% by weight sodium thiocyanate solution, is added to the mold. The solvent from the HP AN I solution causes the outermost surface of the coagulated HP AN II layer surrounding the braided fibers to dissolve and allow commingling of the HP AN I and HP AN II hydrogel polymers at the surface interface which forms a strong adhesive bond when the HP AN I and commingled hydrogels are coagulated by solvent exchange. It should be understood that the reinforcement member is optional and that a mold may be filled without such a reinforcement member.

[0040] Upon completion of the solvent exchange extraction process, the implant may be hydrated to its fullest extent (-90% equilibrium water content (EWC)). In this fully hydrated state the implant is readily deformed under modest loads and the hydrogel, e.g., HP AN I or HP AN II, glass transition temperature (T_g) is well below room temperature. This is the "relaxed" state of the implant, the state to which it will return after loading below the critical level. The critical level is the point at which permanent deformation occurs and is further discussed below. In order to provide a reduced configuration (also referred to herein as the first configuration), the implant may be allowed to dehydrate and enter the xerogel state. A considerable amount of the implant's volume is lost when in the xerogel state as compared to the hydrated state. Advantageously, the fully hydrated implant may be deformed into any desirable insertion shape and the temperature of the implant is lowered below its T_g (near freezing point of water). Such an implant is in a state of "frozen deformation" and it would retain that deformed shape indefinitely. Once the implant is warmed above its T_g, however, the implant would recover to its original memorized configuration.

[0041] The T_g of the hydrogel increases with decreasing water content. This characteristic is exploited by simultaneously raising the T_g while deforming the implant into a desired shape. In other words, as the implant dehydrates it is freezing the position of the polymer chains. To regain the original shape of the implant, the T_g may be lowered by hydration.

[0042] The herein described subject matter sometimes illustrates different components or elements contained within, or connected with, different other components or elements. It is to be understood that such depicted architectures are merely examples, and that in fact many other architectures may be implemented which achieve the same functionality. In a conceptual sense, any arrangement of components to achieve the same functionality is effectively "associated" such that the desired functionality is achieved. Hence, any two components herein combined to achieve a particular functionality may be seen as "associated with" each other such that the desired functionality is achieved, irrespective of architectures or intermedial components.

[0043] Although the invention herein has been described with respect to particular embodiments, it is understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended claims.

Claims

I claim:

1. A pH-sensitive indwelling stomach implant for reducing volume of a stomach, said implant configured to transition from an expanded state to a reduced volume state when exposed to a stomach acid, whereby said implant in said reduced volume state provides for free passage of digested food without blocking of the stomach or a pyloric orifice.

2. The stomach implant as in claim 1, wherein the volume of said implant in said expanded state is greater than the volume thereof in said reduced volume state by two to five times.

3. The stomach implant as in claim 1, wherein said implant is made from an indigestible polymeric material, said implant further having a collapsed state when said polymeric material is dehydrated, said implant when in said collapsed state is suitable for insertion into the stomach.

4. The stomach implant as in claim 3, wherein said implant has a volume from about 0.5 cubic centimeters to about 3 cubic centimeters when in said collapsed state.

5. The stomach implant as in claim 3, wherein said implant transitions from said collapsed state to said expanded state upon being exposed to and absorbing stomach fluids, the volume of said implant in said expanded state is greater than the volume of said implant in said collapsed state by three to twenty times.

6. The stomach implant as in claim 3, wherein said polymeric material is a hydrogel.

7. The stomach implant as in claim 6, wherein said hydrogel contains a carboxyl group.

8. The stomach implant as in claim 6, wherein said polymeric material includes a first less hydrophilic polymer phase and a second more hydrophilic polymer phase, said first less hydrophilic polymer phase has a content of hydrophobic groups higher than a content of hydrophilic groups, said second more hydrophilic polymer phase has a content of hydrophilic groups higher than a content of hydrophobic groups.

9. The stomach implant as in claim 8, wherein at least one polymeric component of said hydrogel is a multiblock copolymer with alternating sequences of hydrophilic and hydrophobic groups.

10. The stomach implant as in claim 6, wherein said implant is a sponge comprising a matrix of a continuous phase formed by a hydrophobic polymer or a hydrophilic polymer with low to medium water content, said implant further including a dispersed phase formed by a highly hydrophilic polymer, said dispersed phase contained inside said matrix of said continuous phase.

11. The stomach implant as in claim 10, wherein a ratio between said continuous phase and said discrete phase is from about 1:2 to about 1:100 on a dry weight basis.

12. The stomach implant as in claim 11, wherein said ratio between said continuous phase and said discrete phase is from about 1:5 to about 1:20.

13. The stomach implant as in claim 1, wherein reduction in stomach acid content causes said implant to transition back from a reduced volume state to an expanded state.

14. The stomach implant as in claim 1 further including voids configured to impart equal or lower density to said implant when compared to stomach fluids density, whereby said implant is buoyant in said stomach fluids.

15. The stomach implant as in claim 1 further comprising an interiorly-embedded reinforcement member.

16. The stomach implant as in claim 15, wherein said reinforcement member is a mesh.

17. The stomach implant as in claim 15, wherein said reinforcement member is a fabric strip.

18. The stomach implant as in claim 15, wherein said reinforcement member extends from an interior of said implant to an exterior thereof, said reinforcement member is further configured for anchoring said implant inside said stomach.

19. The stomach implant as in claim 1 further including radiopaque inclusions configured to improve visibility of said implant when visualized using X-Ray or fluoroscopic techniques.

20. A swellable implant for reducing stomach volume, said implant configured to transition from a dehydrated collapsed state to an expanded state by absorbing stomach fluids, said implant in said collapsed state is sized for insertion into the stomach.