WO2010090097A1

WO2010090097A1 - Antibacterial catheter, and method for manufacturing same

Info

Publication number: WO2010090097A1
Application number: PCT/JP2010/050957
Authority: WO
Inventors: 直人竹村
Original assignee: テルモ株式会社
Priority date: 2009-02-09
Filing date: 2010-01-26
Publication date: 2010-08-12
Also published as: JPWO2010090097A1

Abstract

Disclosed is an antibacterial catheter (1) which is characterized by comprising a tube-shaped main body (2) composed of a polymer material containing an antibacterial agent (3), wherein the antibacterial agent (3) is localized in the vicinity of the inner surface and the vicinity of the outer surface of the main body (2). Also disclosed is a method for manufacturing the antibacterial catheter (1), which is characterized by comprising: a first step of dispersing the antibacterial agent (3) in a swelling organic solvent to prepare an antibacterial agent solution; and a second step of immersing the main body (2) in the antibacterial agent solution to impregnate the vicinity of the inner surface and the vicinity of the outer surface of the main body (2) with the antibacterial agent (3).

Description

Antibacterial catheter and method for producing the same

The present invention relates to an antibacterial catheter and a method for producing the same. In particular, the present invention relates to an antibacterial central venous catheter that is placed in a blood vessel when performing central venous nutrition.

Conventionally, when central parenteral nutrition is performed, bacteria may enter the body through the skin puncture site or lumen of the catheter, causing bacterial infection. Severe infection can result in sepsis. The case where the catheter tip adherent bacteria and the causative bacteria of the sepsis coincide is particularly referred to as catheter-related bacteremia (CR-BSI), and the patient may die due to CR-BSI.

In order to avoid such a problem, when CR-BSI is suspected or diagnosed with CR-BSI, antibiotics are generally administered or a new catheter is exchanged. However, although CR-BSI is a complication at the time of indwelling, the above-mentioned treatment deviates from the original treatment content, which causes a medical cost increase for medical institutions. Therefore, development of a highly antibacterial catheter is desired.

As such an antibacterial catheter, Patent Document 1 describes an in-vivo insertion tube (catheter) having an in-vivo insertion site in which a predetermined amount of an antibacterial agent such as a silver-substituted inorganic ion exchanger is mixed with a base material. ing. Also in Patent Document 2, after absorbing a compound capable of binding to silver ions such as an amino acid derivative, an anionic surfactant, a compound having a carboxyl group or a sulfone group, it is immersed in an aqueous silver compound solution such as silver acetate. Thus, a urinary catheter having a silver compound introduced (coated) on the surface is described.

JP-A-5-220216 (Claims 1 to 4) JP-A-11-290449 (Claims 1 to 5)

However, in the catheters described in Patent Document 1 and Patent Document 2, the binding force of the silver compound (antibacterial agent) to the base material is weak and the particle size of the silver compound (antibacterial agent) is large. The silver compound (antibacterial agent) elutes in a short period of time by chemicals, body fluids, etc. flowing through the catheter lumen. Therefore, there exists a problem that the antimicrobial property of a catheter cannot be maintained at a high level over a long period of time.

Therefore, the present invention was created to solve such problems, and an object thereof is to provide an antibacterial catheter that can maintain antibacterial properties at a high level for a long period of time and a method for manufacturing the same.

In order to solve the above problems, an antibacterial catheter according to claim 1 is an antibacterial catheter including a tube-shaped main body portion made of a polymer material containing an antibacterial agent, and the antibacterial agent is It is unevenly distributed near the inner surface and the outer surface of the main body.

According to the configuration, the antibacterial agent is unevenly distributed in the vicinity of the inner surface and the outer surface of the main body part, so that the amount of the antibacterial agent eluted from the main body part during use can be reduced at the initial stage. The amount is maintained at a high level over time.

The antibacterial catheter according to claim 2 is characterized in that, in the antibacterial catheter, the outer surface of the main body is coated with an antithrombotic material.
According to the said structure, antithrombogenicity is provided in use by being coated with the antithrombogenic material.

In addition, the antibacterial catheter according to claim 3 further includes a tube-like distal end portion that is joined to the distal end side of the main body portion and is more flexible than the main body portion in the antibacterial catheter, The tip portion is made of a polymer material containing an antibacterial agent, and the antibacterial agent exists substantially uniformly from the inner surface to the outer surface of the tip portion.

According to the above configuration, since the antibacterial agent is present substantially uniformly from the inner surface to the outer surface of the tip, not only the amount of the antibacterial agent eluted from the main body during use, but also from the tip. The amount of the antibacterial agent to be eluted can be reduced in the initial stage, and the amount of dissolution can be maintained at a high level for a long time.

The antibacterial catheter according to claim 4 is characterized in that in the antibacterial catheter, an antithrombotic material is coated on outer surfaces of the main body part and the tip part.
According to the said structure, antithrombogenicity is provided in use by being coated with the antithrombogenic material.

The antibacterial catheter according to claim 5 is characterized in that, in the antibacterial catheter, the antibacterial agent is nano silver particles.
According to the said structure, when an antibacterial agent is nano silver particle, the amount of elution of an antibacterial agent at the initial stage can be decreased in use, and the elution amount is maintained at a higher level over a long period of time.

The method for producing an antibacterial catheter according to claim 6 is a method for producing an antibacterial catheter comprising a tube-shaped main body portion made of a polymer material containing an antibacterial agent, wherein the main body portion is made of a polymer material. A first step of preparing an antibacterial agent solution by dispersing the antibacterial agent in a swellable organic solvent, and immersing the main body part in the antibacterial agent solution, And a second step of impregnating the antibacterial agent in the vicinity of the outer surface.

According to the said procedure, by performing the 2nd step which immerses a main-body part in an antibacterial agent solution, the polymeric material which comprises a main-body part swells with a swellable organic solvent, and the swollen main-body part (polymer material) is carried out. Impregnated with antibacterial agent. And by making the impregnated part of the antibacterial agent near the inner surface and the outer surface of the main body part, the antibacterial agent is unevenly distributed near the inner surface and the outer surface of the main body part. As a result, in use, the amount of the antibacterial agent eluted from the main body in the initial stage can be reduced, and the amount eluted can be maintained at a high level over a long period of time.

The antibacterial catheter manufacturing method according to claim 7 is the antibacterial catheter manufacturing method, wherein after the second step, an antithrombotic material is coated on the outer surface of the main body. Is further included.
According to the above procedure, antithrombogenicity is imparted in use by performing the third step of coating the antithrombogenic material.

The method for producing an antibacterial catheter according to claim 8 comprises a tube-shaped main body made of a polymer material containing an antibacterial agent, and is joined to the distal end side of the main body so as to be more flexible than the main body. An antibacterial catheter manufacturing method comprising a tube-shaped tip portion made of a polymer material containing an antibacterial agent, wherein the main body portion and the tip portion are formed of a polymer material, and the antibacterial agent is A first step of preparing an antibacterial agent solution by dispersing in a swellable organic solvent, and separately immersing the main body part and the tip part in the antibacterial agent solution; A second step of impregnating the antibacterial agent in the vicinity and impregnating the antibacterial agent from the inner surface to the outer surface of the tip portion; and a third step of joining the tip portion to the tip side of the main body portion; The And wherein the Mukoto.

According to the above procedure, by performing the second step of immersing the main body part and the tip part in the antibacterial agent solvent, the amount of the antibacterial agent eluted from the main body part at the time of use can be reduced at the initial stage. Is maintained at a high level for a long time. In addition, also in the tip portion, the polymer material constituting the tip portion is swollen by the swellable organic solvent, and the swollen tip portion (polymer material) is impregnated with the antibacterial agent. And by making the impregnation part of the antibacterial agent in the tip part from the inner surface to the outer surface, the antibacterial agent exists substantially uniformly from the inner surface to the outer surface of the tip part. As a result, the amount of the antibacterial agent eluted from the tip during use can be reduced in the initial stage, and the amount of dissolution can be maintained at a high level over a long period of time.

Also, in the second step, the main body part and the tip part are separately immersed in the antibacterial agent solution, and in the third step, the tip part is joined to the tip side of the main body part. Therefore, the tip portion is prevented from excessively swelling and losing flexibility.

An antibacterial catheter manufacturing method according to claim 9 is the antibacterial catheter manufacturing method, wherein after the three steps, an antithrombotic material is coated on the outer surfaces of the main body and the tip. The method further includes a fourth step.
According to the said procedure, antithrombogenicity is provided in use by performing the fourth step of coating the antithrombogenic material.

An antibacterial catheter manufacturing method according to claim 10 is characterized in that, in the antibacterial catheter manufacturing method, the antibacterial agent is nano silver particles.
According to the above procedure, when the antibacterial agent is nano silver particles, the amount of the antibacterial agent eluting from the main body part or both the main body part and the tip part can be reduced at the time of use. The amount is maintained at a higher level over time.

An antibacterial catheter manufacturing method according to claim 11 is characterized in that, in the antibacterial catheter manufacturing method, the swellable organic solvent is hydrophobic.

According to the above procedure, since the swellable organic solvent is hydrophobic, the impregnation of the antibacterial agent is not hindered by moisture adsorbed when the solvent is dried, and in the manufactured antibacterial catheter, in the vicinity of the inner surface of the main body. And the distribution state of the antibacterial agent near the outer surface becomes good. Moreover, the distribution state of the antibacterial agent at the tip is also improved.

According to the antibacterial catheter of the present invention, the growth or infection of bacteria that have entered the body through the skin piercing portion and lumen of the catheter can be suppressed over a long period of time, and the antibacterial activity of the catheter can be maintained at a high level over a long period of time. . Moreover, antithrombogenicity is imparted to the catheter.

According to the method for producing an antibacterial catheter according to the present invention, a catheter in which the growth or infection of bacteria that have entered the body is suppressed for a long period of time and the antibacterial property can be maintained at a high level for a long period of time. In addition, a catheter that does not deform at the tip is manufactured. In addition, a catheter is manufactured that is unlikely to have a site with insufficient antibacterial properties, that is, that does not cause unevenness in antibacterial properties. Furthermore, a catheter provided with antithrombogenicity is manufactured.

It is an external view which shows the structure of the antibacterial catheter which concerns on this invention. FIG. 2 is a sectional view taken along line AA in FIG. 1. FIG. 2 is a sectional view taken along line BB in FIG. It is a graph which shows a time-dependent change of silver elution amount. It is a graph which shows a time-dependent change of an antibacterial activity value.

Embodiments of an antibacterial catheter according to the present invention will be described in detail with reference to the drawings. 1 is an external view showing a configuration of an antibacterial catheter, FIG. 2 is a cross-sectional view taken along the line AA in FIG. 1, and FIG. 3 is a cross-sectional view taken along the line BB in FIG.

As shown in FIGS. 1 and 2, an antibacterial catheter (hereinafter referred to as a catheter) 1 is made of a polymer material containing an antibacterial agent 3, and has a tubular shape in which a lumen 5 through which a drug solution, a body fluid, etc. flows is formed. The main body 2 is provided. And the antibacterial agent 3 is unevenly distributed in the inner surface vicinity 2a and the outer surface vicinity 2b of the main-body part 2. As shown in FIG.

As the polymer material used for the main body 2, a polymer material conventionally used for catheters can be used. For example, as the polymer material, various resins such as polyvinyl chloride, polyurethane, polyamide, polyolefin, polyester, silicon resin, or a resin composition obtained by combining two or more of these can be used. Further, the polymer material may contain a contrast agent for the purpose of ensuring the contrast in the body of the main body 2. As the contrast agent, inorganic compounds such as barium sulfate, barium carbonate, bismuth oxide, bismuth subcarbonate and tungsten are used.

Antibacterial agents used in the main body 2 include metals such as gold, silver, copper and mercury, metal compounds such as titanium oxide, thimerosal and methylobromine, inorganic compounds such as zeolite carrying metal ions, erythromycin and oxytetracycline. , Chloramphenicol, fusidic acid, micamycin, kanamycin, gentamicin, fradiomycin, gramicidin, streptomycin, polymyxin, colistin, antibiotics such as bacitracin, biguanide compounds such as chlorhexidine, benzethonium, benzalkonium, lauryl sulfate, alkylpolyaminoethyl Surface active compounds such as glycine, fatty acids, domifene bromide, phenol derivatives such as thymol, phenol, hexachlorophene, resorcin, boric acid compounds such as boric acid and borax, Iodine, iodoform, iodine compounds such as povidone-iodine, acrinol, antimicrobial dye compounds such Mechirurozarinin, mafenide acetate, sulfadiazine, Surufisomijin, sulfa drugs such as sulfamethoxazole can be used. These antibacterial agents 3 may be salt compounds such as sodium salt, potassium salt, magnesium salt, calcium salt, hydrochloride, sulfate, gluconate, etc., and two or more kinds of antibacterial agents 3 are used in combination. May be. And as the antibacterial agent 3, it is preferable to use the pure silver particle or silver salt particle which is a silver-type particle, and it is more preferable to use nano silver particle or silver salt nano particle. Here, the nano silver particles or silver salt nanoparticles are silver particles having a particle size of 10 ⁻⁹ m to 10 ⁻⁸ m.

Further, the silver-based particles only need to change into pure silver particles due to heat treatment after impregnation and the like. For example, not only pure silver particles but also silver nitrate other than pure silver, silver acetate, silver azide, excess Even silver salt particles of silver chlorate or a mixture thereof may be used as long as they change into pure silver particles by heat treatment after impregnation.

The vicinity of the inner surface 2a and the vicinity of the outer surface 2b of the main body 2 refer to regions in the range of 500 μm from the outermost surface (inner surface or outer surface) in the thickness direction of the main body 2. Further, the fact that the antibacterial agent 3 is unevenly distributed in the vicinity of the inner surface 2a and the vicinity of the outer surface 2b means that 50% or more of the total amount of the antibacterial agent 3 impregnated in the main body 2 by the method described later is impregnated in the region. That means. As described above, when a predetermined amount of the antibacterial agent 3 is unevenly distributed (impregnated) in the vicinity of the inner surface 2a and the outer surface 2b of the main body 2, the amount of the antibacterial agent 3 eluted from the main body 2 is long-term. The antibacterial properties of the catheter 1 can be maintained at a high level over a long period of time.

The amount of impregnation in the vicinity of the inner surface 2a and the outer surface 2b of the antibacterial agent 3 is appropriately set depending on the type of the antibacterial agent 3 to be used, but in the case of using nano silver particles as the antibacterial agent 3, it is 10 to 10,000 ppm. Preferably there is. When the impregnation amount is less than 10 ppm, the elution amount of the nano silver particles is small and the antibacterial property tends to be insufficient. On the other hand, if the impregnation amount exceeds 10,000 ppm, the physical properties of the polymer material constituting the main body part 2 change or it becomes difficult to impregnate the polymer material.

Further, although not shown, the catheter 1 according to the present invention may be one in which the outer surface of the main body 2 is coated with an antithrombotic material. The antithrombotic material coated on the main body 2 is made of a biological material such as a mucopolysaccharide such as heparin or a protein such as urokinase, or a non-biological material such as a water-insoluble nonionic polymer. is there. The water-insoluble nonionic polymer is preferably at least one selected from the group consisting of polyalkoxyalkyl (meth) acrylates, polyalkylene glycols, insolubilized polyalkyl (meth) acrylamides and polyvinylpyrrolidone.

As shown in FIGS. 1 and 3, the catheter 1 according to the present invention further includes a tube-like distal end portion 4 joined to the distal end side of the main body portion 2 and formed with a lumen 5 through which a chemical solution, a body fluid and the like flow. May be. In the present invention, the distal side refers to the side inserted into the body, and the proximal side refers to the side operated by the operator.

The tip portion 4 is made of a polymer material containing the antibacterial agent 3 and is configured more flexibly than the main body portion 2. And the antimicrobial agent 3 exists substantially uniformly from the inner surface 4a of the front-end | tip part 4 to the outer surface 4b (it exists substantially uniformly in the front-end | tip part whole). As a result, as shown in FIGS. 1 to 3, in the catheter 1, the antibacterial agent 3 is unevenly distributed in the vicinity of the inner surface 2a and the vicinity of the outer surface 2b in the main body 2, and from the inner surface 4a to the outer surface 4b in the distal end portion 4. The antibacterial agent 3 exists substantially uniformly. Thereby, the elution amount in the initial stage of the antibacterial agent 3 eluted from the main body 2 and the distal end portion 4 can be reduced, the elution amount can be maintained at a high level for a long time, and the antibacterial property of the catheter 1 can be maintained at a high level for a long time. .

As the polymer material used for the tip portion 4, a polymer material conventionally used in catheters can be used as in the main body portion 2. Further, the polymer material used for the tip portion 4 may be the same or different from the main body portion 2. However, in order to make the tip part 4 more flexible than the main body part 2, the tip part 4 is made thinner than the main body part 2 when it is made of the same kind of polymer material as the main body part 2. It is necessary to take measures such as. The polymer material may contain the above-described contrast agent for the purpose of ensuring the contrast in the body of the tip portion 4.

As the antibacterial agent 3 used for the tip part 4, those exemplified as the antibacterial agent 3 used for the main body part 2 can be used. Further, the antibacterial agent 3 used for the tip portion 4 may be the same as or different from the main body portion 2. Further, the impregnation amount of the antibacterial agent 3 impregnated in the tip 4 by the method described later is appropriately set depending on the type of the antibacterial agent 3 to be used. It is preferably 10,000 ppm. When the impregnation amount is less than 10 ppm, the elution amount of the nano silver particles is small and the antibacterial property tends to be insufficient. On the other hand, if the impregnation amount exceeds 10,000 ppm, the physical properties of the polymer material constituting the tip portion 4 change or it becomes difficult to impregnate the polymer material. The amount of impregnation of the antibacterial agent 3 in the main body 2 (the inner surface vicinity 2a and the outer surface vicinity 2b) is the same as described above.

Further, although not shown, the catheter 1 according to the present invention may be one in which the outer surfaces of the main body 2 and the distal end 4 are coated with an antithrombotic material. The antithrombogenic material coated on the main body portion 2 and the tip portion 4 is made of a biological material or a non-biological material mentioned as the antithrombogenic material coated on the main body portion 2. The same kind of antithrombogenic material may be used for the tip 2 and the tip portion 4, or different kinds of antithrombotic materials may be used.

As shown in FIG. 1, the catheter 1 according to the present invention has a hub 6 joined to the proximal end side of the main body 2 and a distal end side joined to the hub 6 so as to communicate with the lumen 5 of the main body 2. You may further provide the connection tube 7 and the connector 8 joined to the base end side of the connection tube 7, and joined to the infusion set etc. which are not shown in figure. Further, a side hole 9 may be formed on the distal end side of the main body portion 2 for ejecting a chemical solution or the like injected from the connection tube 7 (connector 8) from the main body portion 2 (inner lumen 5) to the outside. . In addition, it is preferable to impregnate the antibacterial agent 3 about the hub 6, the connection tube 7, and the connector 8, particularly in the vicinity of the outer surface thereof, like the main body 2 and the tip 4. Further, the outer surfaces of the hub 6, the connecting tube 7 and the connector 8 may be coated with an antithrombotic material.

The hub 6 and the connector 8 are made of a polymer material such as polypropylene, polyethylene, hard polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, methacryl-acrylonitrile-butadiene-styrene copolymer, polycarbonate, nylon or the like. The connection tube 7 is made of the polymer material exemplified in the main body 2, and may be the same type or different from the main body 2. In the catheter 1 shown in FIG. 1, three lumens 5 are formed inside the main body 2, but the number is not limited to three, and may be two, one, or four. Further, the number of connection tubes 7 is preferably the same as the number of lumens 5.

Next, the manufacturing method of the catheter 1 which concerns on this invention is demonstrated.
First, the manufacturing method of the catheter 1 provided with the main-body part 2 WHEREIN: While forming the main-body part 2 with a polymeric material, disperse | distributing the antibacterial agent 3 in a swellable organic solvent, and adjusting the antibacterial agent solution, A second step of immersing the main body part 2 in the antibacterial agent solution and impregnating the antibacterial agent 3 in the vicinity of the inner surface 2a and the outer surface vicinity 2b of the main body part 2. Moreover, you may further include the 3rd step which coat | covers an antithrombogenic material on the outer surface of the main-body part 2 after a 2nd step. In addition, the contrast property is imparted to the main body 2 by a method in which a polymer material and a contrast agent are formed in multiple layers, a method in which a contrast agent is uniformly dispersed in the polymer material, or the like.

In the first step, the main body 2 is molded by a conventionally known extrusion molding, injection molding or the like using the above-described polymer material, and the main body 2 is molded into a tube shape.

In the first step, the swellable organic solvent used for the preparation of the antibacterial agent solution is an organic solvent that swells the polymer material constituting the main body 2 by dipping in the second step to be described later. Furan (THF), dimethylformamide (DMF), dimethylacetamide, cyclohexanone, methyl ethyl ketone (MEK), dimethyl sulfoxide (DMSO) and the like can be used. The antibacterial agent solution may be a mixed organic solvent obtained by mixing a predetermined amount of acetone, methanol, ethanol (EtOH), isopropanol, diethyl ether, hexane, or the like with the aforementioned swellable organic solvent.

Further, the swellable organic solvent is preferably hydrophobic, and cyclohexanone, MEK, toluene, chloroform, etc. can be used as such an organic solvent. Since the swellable organic solvent is hydrophobic, impregnation of the antibacterial agent 3 into the main body 2 is less likely to be hindered by moisture adsorbed during solvent drying. As a result, the distribution state of the antibacterial agent 3 in the main body 2 (the inner surface vicinity 2a and the outer surface vicinity 2b) becomes good, and the antibacterial properties of the catheter 1 are less likely to be uneven.

In the second step, the main body 2 is immersed in an antibacterial agent solution, and the inner surface vicinity 2a and the outer surface vicinity 2b of the main body 2 are impregnated with the antibacterial agent 3, whereby the inner surface vicinity 2a of the main body 2 and the outer surface A predetermined amount of the antibacterial agent 3 is unevenly distributed in the vicinity of the surface 2b. As a result, the amount of the antibacterial agent 3 eluted from the main body 2 is maintained at a high level over a long period of time, and the antibacterial property of the catheter 1 can be maintained at a high level over a long period of time.

The immersion time of the main body portion 2 in the antibacterial agent solution may be a time sufficient to cause the predetermined amount of the antibacterial agent 3 to be unevenly distributed in the main body portion 2. The immersion time is the concentration of the antibacterial solution used (dispersion amount of the antibacterial agent 3), the type of the swellable organic solvent used in the antibacterial agent solution, and the type of the polymer material constituting the main body 2 Is set as appropriate. For example, when the body part 2 made of polyurethane is immersed by using 100 to 20000 ppm of nano silver colloid solution (EtOH / THF: 1/1 to 9/1) as an antibacterial agent solution, it is immersed for 1 to 60 seconds. Is preferred. By dipping in this way, the main body 2 (inner surface vicinity 2a and outer surface vicinity 2b) is impregnated with a predetermined amount (10 to 10,000 ppm) of nano silver particles.

In the second step, in order to increase the fixing force of the impregnated antibacterial agent 3 to the main body 2 (inner surface vicinity 2a and outer surface vicinity 2b), after the immersion in the antibacterial agent solution is completed, heat treatment is performed. Preferably it is done. As treatment conditions for the heat treatment, treatment conditions that do not change the physical properties of the main body 2 and do not deteriorate the antibacterial agent 3 are appropriately selected. For example, when polyurethane is used for the main body 2 and nano silver particles are used as the antibacterial agent 3, (80 to 180 ° C.) × (10 minutes to 24 hours) is preferable. In addition, after the main body 2 is impregnated with the antibacterial agent 3, the hub 6, the connecting tube 7 and the connector 8 are bonded using an adhesive, bonding with heat or ultrasonic waves, fitting by heat shrinking, or the like. It may be joined to the main body 2 with

In the third step, as a method of coating the main body 2 with the antithrombotic material, a method of coating a solution in which the antithrombotic material is dissolved by a dipping method, a spray method, or the like is used. Examples of the solvent that dissolves the antithrombotic material include organic solvents such as acetone, methanol, ethanol, isopropanol, tetrahydrofuran, N, N-dimethylformamide, N, N-dimethylacetamide, and cyclohexanone. The hub 6, the connection tube 7 and the outer surface of the connector 8 may be coated with an antithrombotic material.

Next, the manufacturing method of the catheter 1 provided with the main-body part 2 and the front-end | tip part 4 shape | molds the main-body part 2 and the front-end | tip part 4 with a polymeric material, and disperse | distributes the antibacterial agent 3 in a swelling organic solvent, and antibacterial agent solution The first step of adjusting the body part 2 and the tip part 4 are separately immersed in the antibacterial agent solution, and the main body part 2 is impregnated with the antibacterial agent 3 in the vicinity of the inner surface 2a and the vicinity of the outer surface 2b, and The tip portion 4 includes a second step of impregnating the antibacterial agent 3 from the inner surface 4a to the outer surface 4b and a third step of joining the tip portion 4 to the tip side of the main body portion 2. Moreover, you may further include the 4th step which coat | covers an antithrombogenic material on the outer surface of the main-body part 2 and the front-end | tip part 4 after a 3rd step. In addition, the imparting of contrast to the main body 2 and the distal end 4 is performed by the same method as the main body 2 described above.

In the first step, the main body 2 and the front end 4 are molded by a conventionally known extrusion molding, injection molding or the like using the above-described polymer material, and the main body 2 and the front end 4 are formed into a tube shape. The

In the first step, the swellable organic solvent used for the preparation of the antibacterial agent solution is the same as described above. In addition, the same type of antibacterial agent solution may be adjusted between the main body 2 and the tip portion 4, or different types of antibacterial agent solutions may be adjusted. Here, the different types of antibacterial agent solutions include those having different concentrations of the antibacterial agent solution (dispersion amount of the antibacterial agent), different swellable organic solvents to be used, and different types of antibacterial agents to be dispersed. . Furthermore, the swellable organic solvent is preferably hydrophobic as described above.

In the second step, the main body 2 and the tip 4 are separately immersed in the antibacterial agent solution. Thereby, the immersion conditions (for example, the kind of antibacterial agent solution, immersion time) of the front-end | tip part 4 comprised more flexibly than the main-body part 2 are not influenced by the immersion conditions of the main-body part 2, in other words, the main-body part 2 and The tip portion 4 can be immersed in the antibacterial agent solution under different immersion conditions. As a result, the immersion condition of the distal end portion 4 does not become excessive, and the distal end portion 4 does not swell excessively and lacks flexibility, so that deformation of the distal end portion 4 (catheter 1) can be prevented.

In the second step, the main body 2 is impregnated with the antibacterial agent 3 near the inner surface 2a and the outer surface 2b, and the tip 4 is impregnated with the antibacterial agent 3 from the inner surface 4a to the outer surface 4b. . As a result, the antibacterial agent 3 is unevenly distributed in the vicinity of the inner surface 2a and the outer surface 2b in the main body portion 2, and the antibacterial agent 3 exists substantially uniformly from the inner surface 4a to the outer surface 4b in the tip portion 4. As a result, the elution amount of the antibacterial agent 3 eluted from the main body 2 and the distal end portion 4 is maintained at a high level over a long period, and the antibacterial property of the catheter 1 can be maintained at a high level over a long period.

The immersion time of each of the main body portion 2 and the tip portion 4 in the antibacterial agent solution may be a time sufficient to cause the antibacterial agent 3 to be unevenly distributed in the main body portion 2 and substantially uniform in the tip portion 4. The soaking time is determined by the concentration of the antibacterial agent solution used (dispersion amount of the antibacterial agent 3), the type of the swellable organic solvent used in the antibacterial agent solution, and the high amount constituting the main body 2 and the tip 4. It is set as appropriate in consideration of the type of molecular material. For example, in the main body portion 2 made of polyurethane, the nano silver colloid solution 100 to 20000 ppm (EtOH / THF: 1/1 to 9/1) is used as an antibacterial agent solution and immersed for 1 to 60 seconds, and then made of polyurethane. The tip 4 is preferably immersed for 1 to 60 seconds using a nanosilver colloid solution of 100 to 20000 ppm (EtOH / THF: 1/1 to 9/1). By soaking, the main body 2 (inner surface vicinity 2a and outer surface vicinity 2b) and the tip 4 are impregnated with a predetermined amount (10 to 10,000 ppm) of nano silver particles.

In the second step, the immersion of the impregnated antibacterial agent 3 in the antibacterial agent solution is completed in order to increase the fixing force of the impregnated antibacterial agent 3 to the main body part 2 (inner surface vicinity 2a and outer surface vicinity 2b) and the tip part 4. Then, it is preferable to heat-treat each of the main body 2 and the tip 4. As treatment conditions for the heat treatment, treatment conditions that do not change the physical properties of the main body portion 2 and the tip portion 4 and do not deteriorate the antibacterial agent 3 are appropriately selected. For example, when a polyurethane material is used for the main body 2 and the tip 4 and nano silver particles are used as the antibacterial agent 3, (80 to 180 ° C.) × (10 minutes to 24 hours) is preferable. Further, the processing conditions may be different between the main body 2 and the tip 4.

In the third step, the joining method used in the manufacture of a conventional catheter is used as the joining method between the main body 2 and the tip 4. For example, a bonding method such as bonding using an adhesive, fusion by heat or ultrasonic waves, fitting by heat shrinkage, or the like is used. The same applies to the method of joining the hub 6, the connecting tube 7 and the connector 8.

In the fourth step, a method similar to the method of coating the main body 2 with the antithrombogenic material is used as a method of coating the main body 2 and the tip 4 with the antithrombogenic material. Then, the coating on the main body 2 and the coating on the tip 4 may be performed simultaneously or separately. The outer surfaces of the hub 6, the connecting tube 7 and the connector 8 may be similarly coated with an antithrombogenic material.

Next, a method for using the catheter according to the present invention will be described taking a central venous catheter used for central venous nutrition as an example. In general, there are two methods of using a central venous catheter (insertion method into a blood vessel) used for central venous nutrition, although not shown. The first method is to introduce a central venous catheter into the blood vessel through the outer lumen while the outer needle is removed after introducing a puncture needle having a separable outer tube into the blood vessel and leaving the outer mantle. Through the cannula method). Secondly, after the indwelling needle having a mantle tube is introduced into the blood vessel, the inner needle is removed, the guide wire is introduced into the blood vessel with the mantle remaining, and the guide wire is removed after the mantle is removed. In this method, a central venous catheter is inserted and the guide wire is removed (Seldinger method). In the catheter of the present invention, any method can be preferably used.
The catheter according to the present invention can be preferably used not only for central venous catheters but also for catheters inserted and placed in the body, such as urethral catheters and gastric tube catheters.

Next, examples and comparative examples of the catheter according to the present invention will be described.
(Example)
A polyurethane tube having an outer diameter of 2.5 mm and an inner diameter of 1.75 mm was produced using polyurethane (manufactured by Nippon Milactone Co., Ltd., trade name: E990). Next, a nano silver colloid solution (Nanopoly Co., Ltd., trade name Nanomix, 6000 ppm ethanol solution) was mixed with MEK at a mixing ratio of 1: 1 to obtain an antibacterial agent solution. Then, the polyurethane tube was immersed in an antibacterial agent solution for 1 min to impregnate the polyurethane tube with nanosilver particles, and then heat-treated at 150 ° C. for 30 minutes to obtain a nanosilver-impregnated tube. A catheter was manufactured using this nanosilver-impregnated tube as the main body of the catheter.

(Comparative example)
The same nanosilver colloid solution as in the example was mixed with ethanol at a mixing ratio of 1: 1 to prepare an antibacterial agent solution. And it coated on the polyurethane tube similar to an Example, Then, 150 degreeC * 30 minute heat processing was performed, and it was set as the nano silver coating tube. The nanosilver coated tube was used as the main body of the catheter to produce a catheter.

Samples with a total surface area of 32 ± 5 cm ² were cut from the catheters produced in the examples and comparative examples, and the samples were immersed in a suspension in S. aureus. After immersion for a predetermined period, using this microbial suspension and the sample, the amount of elution of silver (ppm / day) and the antibacterial activity value were measured over time. The silver elution amount was measured using an ICP emission analyzer (manufactured by Seiko Instruments Inc.), and the antibacterial activity value was measured using the shake method defined in the Antibacterial Test Technology Council Standard. The results are shown in FIG. 4 and FIG. FIG. 4 is a graph showing the change over time in the silver elution amount, and FIG. 5 is a graph showing the change over time in the antibacterial activity value.

As shown in FIG. 4 and FIG. 5, the catheter of the example has a high antibacterial activity value because the silver elution amount is at a high level even after the immersion time of 20 days, compared with the catheter of the comparative example. It was confirmed that antibacterial properties were maintained over the entire period.

1 Antibacterial catheter (catheter)
2 Main body 2a Near inner surface 2b Near outer surface 3 Antibacterial agent 4 Tip 4a Inner surface 4b Outer surface

Claims

An antibacterial catheter comprising a tube-shaped main body made of a polymer material containing an antibacterial agent, wherein the antibacterial agent is unevenly distributed near the inner surface and the outer surface of the main body portion Catheter.
The antibacterial catheter according to claim 1, wherein the outer surface of the main body is coated with an antithrombotic material.
The tube further includes a tube-shaped tip that is joined to the tip of the body and is more flexible than the body. The tip is made of a polymer material containing an antibacterial agent, and the antibacterial agent is the tip. The antibacterial catheter according to claim 1, wherein the antibacterial catheter is present substantially uniformly from the inner surface to the outer surface.
The antibacterial catheter according to claim 3, wherein an antithrombotic material is coated on the outer surfaces of the main body and the tip.
The antibacterial catheter according to any one of claims 1 to 4, wherein the antibacterial agent is nano silver particles.
An antibacterial catheter manufacturing method comprising a tube-shaped main body portion made of a polymer material containing an antibacterial agent,
A first step of forming the main body portion with a polymer material and dispersing the antibacterial agent in a swellable organic solvent to prepare an antibacterial agent solution;
A method of manufacturing an antibacterial catheter, comprising: a second step of immersing the main body part in the antibacterial agent solution and impregnating the antibacterial agent in the vicinity of the inner surface and the outer surface of the main body part.
The method for manufacturing an antibacterial catheter according to claim 6, further comprising a third step of coating the outer surface of the main body with an antithrombogenic material after the second step.
A tube-shaped main body portion made of a polymer material containing an antibacterial agent, and a tube-shaped tip portion made of a polymer material containing an antibacterial agent, which is joined to the distal end side of the main body portion and is configured more flexibly than the main body portion A method for producing an antibacterial catheter comprising:
A first step of adjusting the antibacterial agent solution by dispersing the antibacterial agent in a swellable organic solvent while molding the main body and the tip with a polymer material;
The main body and the tip are separately immersed in the antibacterial agent solution, the main body is impregnated with the antibacterial agent in the vicinity of the inner surface and the outer surface, and the tip is from the inner surface. A second step of impregnating the antibacterial agent to the outer surface;
And a third step of joining the distal end to the distal end side of the main body.
9. The method of manufacturing an antibacterial catheter according to claim 8, further comprising a fourth step of coating the outer surface of the main body portion and the distal end portion with an antithrombogenic material after the three steps. .
The method for producing an antibacterial catheter according to any one of claims 6 to 9, wherein the antibacterial agent is nano silver particles.
The method for producing an antibacterial catheter according to any one of claims 6 to 9, wherein the swellable organic solvent is hydrophobic.