JP2012161372A - Medical instrument and method for manufacturing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medical instrument in which a hydrophilic polymer is strongly fixed on the surface of a substrate comprising a polyamide.SOLUTION: The medical instrument includes: a substrate at least a part of the surface of which is the polyamide; an adhesive layer formed on the surface of the substrate and including a polyamide soluble in an organic solvent; and a crosslinked, surface lubricated layer formed on the upper part of the adhesive layer, and including the hydrophilic polymer having at least one reactive functional group selected from the group consisting of an epoxy group, acid chloride group, and isocyanate group, and the method for manufacturing it is provided.

Description

  The present invention relates to a medical device and a manufacturing method thereof.

  In recent years, a balloon catheter having a balloon at the tip is frequently used as a medical device for expanding a stenosis part such as a blood vessel or a bronchus. For the purpose of improving the operability for accessing the target site of the balloon catheter and reducing tissue damage to the inner wall of the blood vessel, a low friction material is used for the balloon base material or the balloon surface is reduced. In order to make friction, a method of coating a balloon base material with a lubricating material such as a lubricant, a low friction resin, and a hydrophilic polymer has been studied.

  The method of applying a lubricating material such as fluororesin, silicone resin, silicone oil, olive oil, or glycerin to the substrate surface is a simple method, but the lubricant is detached from, peeled from, or eluted from the substrate surface. There are many problems in terms of safety and sustainability.

  Recently, a method for producing a low-friction surface by coating and reacting a hydrophilic polymer to form a hydrogel on the surface has been studied. For example, Patent Document 1 discloses a method of coating a substrate surface with a hydrophilic polymer (polyvinylpyrrolidone) using isocyanate. In addition, a method of coating a hydrophilic polymer copolymerized with a reactive functional group using isocyanate (see Patent Document 2), a method of coating polyethylene oxide (see Patent Document 3), and the like are disclosed. In Patent Document 4, a copolymer such as polyether, polyamide, or polysiloxane is provided on a surface on which at least one of an amino group, an imino group, a carboxyl group, and a mercapto group is present via a polyisocyanate. A method of bonding is described. In Patent Document 5, a polymer having a reactive functional group (component A) is applied to a substrate surface, and then a hydrophilic polymer having a reactive functional group capable of reacting with the reactive functional group (component B) is coated. How to do is described.

  Furthermore, Patent Document 6 describes a technique in which alcohol-soluble nylon is applied as an adhesive layer on the surface of a base material constituting a medical device, and a modified product of maleic anhydride copolymer is further coated as an outermost surface layer. ing.

U.S. Pat. No. 4,100,309 JP 59-81341 A JP 58-193766 Japanese Patent Publication No. 1-55023 International Publication No. 90/01344 Pamphlet JP 2008-279100 A

  However, in the techniques described in Patent Documents 1 to 6, the hydrophilic polymer present on the surface of the medical device undergoes a phenomenon such as detachment, peeling, and elution from the surface of the base material, which is called safety and durability. There was a problem in terms. In particular, when a highly crystalline resin such as polyamide is used for the base material, the above phenomenon is remarkable.

  Furthermore, in the technique described in Patent Document 6, a high temperature of 100 to 200 ° C. is required to crosslink the alcohol-soluble nylon used in the adhesive layer, and the base material of the medical device is melted or deformed. There was a problem that occurred.

  Therefore, an object of the present invention is to provide a medical device in which a hydrophilic polymer (hereinafter also referred to as “hydrophilic polymer”) is firmly fixed on the surface of a base material made of polyamide.

  Moreover, the other object of this invention is to provide the manufacturing method of the medical device which can suppress the fusion | melting and deformation | transformation of the base material containing polyamide.

  In view of the above problems, the present inventors have made extensive studies. As a result, after forming an adhesive layer containing a polyamide that dissolves in an organic solvent on a substrate whose surface is at least part of a polyamide, the surface is further selected from the group consisting of an epoxy group, an acid chloride group, and an isocyanate group By covering the hydrophilic polymer having at least one reactive functional group and crosslinking the hydrophilic polymer at a low temperature, a medical device in which the hydrophilic polymer is firmly fixed to the base material is obtained. As a result, the present invention has been completed.

  That is, the present invention provides a base material in which at least a part of the surface is polyamide, an adhesive layer formed on the surface of the base material and containing polyamide that is dissolved in an organic solvent, and formed on the adhesive layer. A surface lubricating layer containing a hydrophilic polymer having at least one reactive functional group selected from the group consisting of a group, an acid chloride group, and an isocyanate group, and a crosslinked hydrophilic polymer. is there.

  Further, the present invention provides an epoxy group after a step of applying and drying a solution containing a polyamide that dissolves in an organic solvent on the surface of a base material in which at least a part of the surface is polyamide, and after the step of applying and drying, A step of applying a solution containing a hydrophilic polymer having at least one reactive functional group selected from the group consisting of an acid chloride group and an isocyanate group; A method for producing a medical device, comprising a step of crosslinking at a temperature.

  ADVANTAGE OF THE INVENTION According to this invention, the medical device by which the hydrophilic polymer was firmly fixed to the base-material surface which consists of polyamides can be provided.

  Moreover, according to this invention, the manufacturing method of the medical device which can suppress the fusion | melting and deformation | transformation of the base material containing polyamide can be provided.

It is a schematic diagram which shows the friction measuring machine used for surface lubrication sustainability evaluation. It is drawing which shows the surface lubrication sustainability evaluation result of the tube (sample) obtained in Example 1. FIG. It is drawing which shows the surface lubrication sustainability evaluation result of the tube (sample) obtained by the comparative example 1.

  The present invention includes a base material in which at least a part of the surface is a polyamide, an adhesive layer formed on the surface of the base material and including a polyamide (hereinafter, also simply referred to as a soluble polyamide) dissolved in an organic solvent, and the adhesive layer A surface lubrication layer comprising a hydrophilic polymer which is formed on the top of the substrate and has at least one reactive functional group selected from the group consisting of an epoxy group, an acid chloride group, and an isocyanate group, and is crosslinked. , Including a medical device.

  In the medical device of the present invention, the hydrophilic polymer existing on the outermost surface is cross-linked, and it is considered that the hydrophilic polymer and the soluble polyamide form an interpenetrating network structure. Therefore, the medical device of the present invention can be a medical device in which the surface lubricating layer is firmly fixed to the polyamide forming the surface of the base material via the adhesive layer.

  Furthermore, since the medical device of the present invention has a lubricious surface, it is excellent in reachability to a target site and minimally invasiveness to a living tissue (such as an inner wall of a blood vessel). In addition, the surface lubricating layer that forms a hydrogel when wet also has a function as a drug reservoir. Therefore, the medical device of the present invention is also suitably used as a balloon catheter for drug administration.

  The hydrophilic polymer present on the outermost surface of the medical device of the present invention is crosslinked at a low temperature of 10 ° C. or more and less than 100 ° C. For this reason, the production method of the present invention is deformed under thin high-temperature conditions such as medical devices that use polyamide on the substrate surface that causes deformation or melting at low temperatures, balloon catheter balloons, microcatheters, guide wires, etc. Even a medical device having a shape that can be easily applied can be applied.

  Hereinafter, the medical device of the present invention will be described in more detail. However, the present invention is not limited to the following form.

<Base material>
"At least a part of the surface of the base material is polyamide" means that at least a part of the surface of the base material is composed of polyamide, and the whole base material (all) is composed (formed) of polyamide. You are not limited to what you have. Therefore, on the surface of a base material formed of a hard reinforcing material such as a metal material or a ceramic material, a flexible polyamide is suitable for the surface of the base material made of a reinforcing material such as a metal material (dipping (dipping), spraying (spray), Conventionally known methods such as coating and printing), or the base metal material and the polyamide are combined (appropriate reaction treatment), and at least a part of the surface is made of polyamide. Some are also included in the substrate of the present invention. In addition, the base material may be a multilayer structure in which different materials are laminated in multiple layers, or a structure (composite) in which members formed of different materials for each part of the medical device are connected.

  The polyamide that can be used for the base material is not particularly limited as long as it is insoluble in an organic solvent, and is an optimal base material according to the use of a catheter such as a balloon catheter, a guide wire, or an indwelling needle. As long as the function can be sufficiently expressed, it may be appropriately selected. Examples thereof are not particularly limited as long as the polymer is insoluble in an organic solvent and has an amide bond. For example, polytetramethylene adipamide (nylon 46), polycaprolactam (nylon 6), polyhexamethylene Single weights such as adipamide (nylon 66), polyhexamethylene sebamide (nylon 610), polyhexamethylene dodecamide (nylon 612), polyundecanolactam (nylon 11), polydodecanolactam (nylon 12) Caprolactam / lauryl lactam copolymer (nylon 6/12), caprolactam / aminoundecanoic acid copolymer (nylon 6/11), caprolactam / ω-aminononanoic acid copolymer (nylon 6/9), caprolactam / hexa Methylenediammonium adipate copolymerization (Nylon 6/66) copolymer such as a copolymer of adipic acid and meta-xylylenediamine, or hexamethylene diamine and m, and aromatic polyamides such as a copolymer of p- phthalic acid.

  Further, a polyamide elastomer which is a block copolymer having nylon 6, nylon 66, nylon 11, nylon 12 or the like as a hard segment and polyalkylene glycol, polyether or aliphatic polyester as a soft segment also relates to the present invention. Used as a base material for medical devices. The said polyamide may be used individually by 1 type, and may use 2 or more types together.

  The polyamide may be a synthetic product or a commercial product. Examples of commercially available products include, for example, polyamides such as RILSAN (registered trademark) AECNO TL (manufactured by ARKEMA, nylon 12), grill amide L25 (manufactured by MSK Japan), grill amide ELY2475, grill amide ELG 5660, grill amide ELG 6260 (or more) And polyamide elastomers such as Ms. Chemie Japan Co., Ltd.).

  Examples of materials other than polyamide used for the base material include various metal materials such as various stainless steels (SUS) such as SUS304, gold, platinum, silver, copper, nickel, cobalt, titanium, and alloys thereof, and various ceramic materials. Inorganic materials such as metal-ceramic composites, polyethylene resins such as linear low density polyethylene, low density polyethylene, and high density polyethylene, and polyolefin resins such as polypropylene resin, epoxy resins, urethane resins, diallyl phthalate resins (allyl resins) , Polycarbonate resin, fluorine resin, amino resin (urea resin, melamine resin, benzoguanamine resin), polyester resin, styrene resin, acrylic resin, polyacetal resin, vinyl acetate resin, phenol resin, vinyl chloride resin, silicone resin (Silicone resin), polyimide resin, polyphenylene sulfide, a polymer material such as polyether sulfone. These may be used singly or in combination of two or more, and an appropriate material is appropriately selected as a base material for catheters such as balloon catheters, guide wires, and indwelling needles that are used. That's fine.

  In particular, when the medical device is a balloon catheter, the balloon substrate may have a multilayer structure as long as polyamide is present on the surface. When using multiple layers, the base material should be made of polyester resin, polyimide resin, polyphenylene sulfite, polyethersulfone, etc., in order to improve the pressure resistance or to create a balloon (non-compliant type) that suppresses deformation due to pressure. It can be multilayered.

  The hydrophilic polymer contained in the surface lubricating layer present on the outermost surface of the medical device of the present invention has at least one reactive functional group selected from the group consisting of an epoxy group, an acid chloride group, and an isocyanate group. It crosslinks easily at a low temperature of 10 ° C. or more and less than 100 ° C. Therefore, for example, nylon 12 which is a material that has a low melting point of about 176 ° C. and easily deforms or melts under a high temperature condition of 100 to 200 ° C. can be used as the substrate. Also, the shape of the substrate can be applied even if it has a shape that is easily deformed under high temperature conditions, such as a balloon of a balloon catheter.

<Polyamide dissolved in organic solvent>
The polyamide (soluble polyamide) used in the adhesive layer of the present invention is soluble in an organic solvent.

  Examples of the organic solvent include methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, t-butyl alcohol, and other alcohols, N, N′-dimethylformamide (DMF), N, N′-dimethylacetamide. (DMAc), methylene chloride, chloroform, acetone, tetrahydrofuran (THF), at least one selected from the group consisting of dioxane, toluene, xylene, benzene and hexane. More preferably, they are methanol, ethanol, n-propyl alcohol, and THF, and more preferably, both the soluble polyamide and the hydrophilic polymer described later are easily dissolved, and they are easily entangled to form an interpenetrating network structure. From this point, it is THF.

  As an example of the soluble polyamide, for example, polyamide which is a block copolymer having nylon 6, nylon 66, nylon 11, nylon 12 or the like as a hard segment and polyalkylene glycol, polyether or aliphatic polyester as a soft segment. Examples thereof include elastomers, N-alkoxymethylated nylons such as N-methoxymethylated nylon and N-ethoxymethylated nylon, and water-soluble nylon.

  These may be used alone or in combination of two or more. Of these, polyamide elastomers are more preferable from the viewpoints of solubility in organic solvents, particularly THF, and adhesion to a substrate.

  As the polyamide soluble in the organic solvent, a synthetic product or a commercially available product may be used. Examples of commercially available products include N-alkoxymethylated nylon (N-methoxy) such as polyamide elastomer (polyether ester amide) such as TPAE-826 (manufactured by Fuji Kasei Kogyo Co., Ltd.) and Toresin F (manufactured by Nagase Chemx). And water-soluble nylon such as methylated nylon) and AQ nylon (manufactured by Toray Industries, Inc.).

  In the present specification, being soluble in an organic solvent means that at 25 ° C., the solubility in at least THF is 0.1% by weight or more. The term “insoluble in an organic solvent” means that the solubility in THF at 25 ° C. is less than 0.1% by weight.

  The soluble polyamide may be cross-linked or non-cross-linked. However, it is preferably non-crosslinked because it is easy to form an interpenetrating network structure by being entangled with a hydrophilic polymer described later.

<Hydrophilic polymer>
The hydrophilic polymer used in the present invention has at least one reactive functional group selected from the group consisting of an epoxy group, an acid chloride group, and an isocyanate group in the molecule, and is crosslinked. The hydrophilic polymer is, for example, a copolymer of a monomer having at least one reactive functional group selected from the group consisting of an epoxy group, an acid chloride group, and an isocyanate group and a hydrophilic monomer. Can be obtained.

(Monomer having a reactive functional group)
Examples of the monomer having a reactive functional group include, for example, a monomer having an epoxy group such as glycidyl acrylate and glycidyl methacrylate; a monomer having an acid chloride group such as acrylic acid chloride and methacrylic acid chloride A monomer having an isocyanate group in the molecule such as acryloyloxyethyl isocyanate; Among them, the crosslinking reaction is moderately accelerated at a temperature of 10 ° C. or more and less than 100 ° C., and further, a surface lubricating layer can be easily formed by insolubilization by forming a crosslinked structure, and handling is relatively easy. Monomers having an epoxy group such as glycidyl acrylate and glycidyl methacrylate are preferred. Hydrophilic polymers using monomers with epoxy groups have a slower reaction rate when crosslinking compared to hydrophilic polymers using monomers with isocyanate groups in the molecule (appropriate rate) It is. Therefore, in the cross-linking reaction between the reactive functional groups, it is possible to suppress and control the gelation by reacting immediately or gelling or solidifying to increase the cross-linking density of the surface lubricating layer and lower the lubricity. Since the reaction rate is moderate (appropriate rate), it can be said that the handleability is good. These monomers having reactive functional groups may be used alone or in combination of two or more.

(Hydrophilic monomer)
The hydrophilic monomer may be any as long as it exhibits lubricity in body fluids and aqueous solvents, such as acrylamide and derivatives thereof, vinyl pyrrolidone, acrylic acid and methacrylic acid and derivatives thereof, sugar, phosphorus A monomer having a lipid in the side chain can be exemplified. For example, N-methylacrylamide, N, N-dimethylacrylamide, acrylamide, acryloylmorpholine, N, N-dimethylaminoethyl acrylate, vinylpyrrolidone, 2-methacryloyloxyethylphosphorylcholine, 2-methacryloyloxyethyl-D-glycoside, 2-Methacryloyloxyethyl-D-mannoside, vinyl methyl ether, hydroxyethyl methacrylate and the like can be suitably exemplified. Of these, N, N-dimethylacrylamide is preferred from the viewpoint of ease of synthesis and operability. These hydrophilic monomers may be used individually by 1 type, and may use 2 or more types together.

  The form of the copolymer (hydrophilic polymer) formed from the monomer having the reactive functional group and the hydrophilic monomer is a block copolymer, a random copolymer, a graft copolymer, Any of alternating copolymers may be used. However, in order to develop good lubricity, the hydrophilic polymer is composed of a domain (block) formed from a hydrophilic monomer and a domain (block) formed from a monomer having a reactive functional group. Are preferably block copolymers or graft copolymers. When such a block copolymer or graft copolymer is used, the strength and lubricity of the surface lubricating layer are further improved.

  The production method (polymerization method) of the hydrophilic polymer is not particularly limited. For example, a living radical polymerization method, a polymerization method using a macromonomer, and a polymer polymer initiator such as a macroazo initiator are used. Conventionally known polymerization methods such as a combination method and a polycondensation method can be applied.

[Method for manufacturing medical devices]
The method for producing a medical device of the present invention comprises a step of applying a solution containing a polyamide that dissolves in an organic solvent to the surface of a substrate whose surface is at least part of a polyamide, an epoxy group, an acid chloride group, and an isocyanate group. A step of applying a hydrophilic polymer having at least one reactive functional group selected from the group consisting of: a step of crosslinking the hydrophilic polymer at a temperature of 10 ° C. or higher and lower than 100 ° C.

  Hereinafter, although the manufacturing method of the medical device of this invention is demonstrated in order of a process, this invention is not limited to the following forms.

<The process of apply | coating the polyamide (soluble polyamide) which melt | dissolves in an organic solvent>
In this step, a solution containing polyamide (soluble polyamide) that dissolves in an organic solvent is applied to a base material having at least a part of the surface of polyamide. Application | coating should just be performed to the polyamide surface part of a base material, and does not necessarily need to be performed to the whole base material. The soluble polyamide contained in the applied solution forms an adhesive layer on the surface of the substrate by drying.

  The solvent used in the solution is not particularly limited, and examples thereof include alcohols such as methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, and t-butyl alcohol, DMF, DMAc, methylene chloride, chloroform, and acetone. , THF, dioxane, toluene, xylene, benzene, hexane and the like. These may be used alone or in combination of two or more. Among these, from the viewpoint of solubility of the soluble polyamide, methanol, ethanol, n-propyl alcohol, and THF are preferable, and THF is more preferable.

  The concentration of the soluble polyamide in the solution is not particularly limited, but is preferably 0.1 to 20% by weight, more preferably 0.5 to 15% by weight, and still more preferably, from the viewpoint of uniform application to a desired thickness. Is 1 to 10% by weight. However, even if it is out of this range, it can be sufficiently utilized as long as it does not affect the operational effects of the present invention.

  The method for applying a solution containing a soluble polyamide to a substrate is not particularly limited. For example, a dipping method (dipping method), a coating / printing method, a spraying method (spray method), a spin coating method, a mixed solution-impregnated sponge coating method. For example, a conventionally known method can be applied. Of these, the dipping method is preferred.

  When the immersion method (dipping method) is used, the immersion time in the solution containing the soluble polyamide is not particularly limited, but is preferably 5 seconds to 30 minutes, and more preferably 5 seconds to 5 minutes.

  After application, the solution is dried to form an adhesive layer. The drying temperature and drying time are not particularly limited, but the drying temperature is preferably 20 to 80 ° C., and the drying time is preferably 15 minutes to 5 hours. Examples of the apparatus used for drying include an oven, a dryer, and a microwave heating apparatus.

  The thickness of the adhesive layer formed in this step is preferably 0.01 to 10 μm, more preferably 0.1 to 1.0 μm. If it is this range, a base material and a surface lubricating layer can be adhere | attached firmly.

<Process for coating hydrophilic polymer>
In this step, a hydrophilic polymer having at least one reactive functional group selected from the group consisting of an epoxy group, an acid chloride group, and an isocyanate group is coated on the base material on which the adhesive layer is formed. . The coated hydrophilic polymer forms a surface lubricating layer on the outermost surface of the base material by crosslinking in a process described later.

  Here, the surface lubricating layer may be formed so as to cover the entire surface of the base material, but may be formed only on the surface portion where the surface is required to have lubricity when wet.

  In particular, when the medical device is a balloon catheter, the surface lubrication layer does not need to be formed on the entire balloon, and may be partially formed on a tapered portion or the like on the distal end side or the base side of the balloon. In particular, when dilating a blood vessel, it is preferable not to cover the entire balloon with a hydrophilic polymer when considering retention at a target site. On the other hand, when a drug is administered for the purpose of suppressing restenosis of dilated blood vessels, it is preferable to coat the entire balloon with a hydrophilic polymer.

  When forming a surface lubricating layer made of a hydrophilic polymer having the reactive functional group, a solution in which the hydrophilic polymer having the reactive functional group is dissolved (hereinafter also abbreviated as “hydrophilic polymer solution”). After the base material with the adhesive layer formed therein is dipped, it is dried and crosslinked to form a surface lubricating layer containing a hydrophilic polymer, and at the same time, the surface lubricating layer is firmly attached to the base material. Can be immobilized. In addition, while the base material on which the adhesive layer is formed is immersed in the hydrophilic polymer solution, the inside of the system is depressurized and degassed, thereby medical devices such as catheters such as balloon catheters, guide wires, and indwelling needles. Alternatively, the solution may be quickly infiltrated into the narrow and narrow inner surface to promote the formation of the surface lubricating layer.

  For example, instead of the method (immersion method or dipping method) of immersing the substrate on which the adhesive layer is formed in the hydrophilic polymer solution, for example, coating / printing method, spraying method (spraying method), spin coating method, mixing By applying a conventionally known method such as a solution-impregnated sponge coating method, the hydrophilic polymer can be coated on the substrate.

  Examples of the solvent used in the hydrophilic polymer solution include DMF, chloroform, acetone, THF, dioxane, benzene and the like. These may be used alone or in combination of two or more. Among these, THF is preferable because both soluble polyamide and hydrophilic polymer are easily dissolved and both are entangled to easily form an interpenetrating network structure.

  The concentration of the hydrophilic polymer solution used when forming the surface lubricating layer is not particularly limited. From the viewpoint of uniformly coating the desired thickness, the concentration of the hydrophilic polymer in the hydrophilic polymer solution is 0.1 to 20% by weight, preferably 0.5 to 15% by weight, more preferably 1 -10% by weight. When the concentration of the hydrophilic polymer solution is less than 0.1% by weight, it is necessary to repeat the above-described dipping operation a plurality of times in order to obtain a surface lubricating layer having a desired thickness. is there. On the other hand, if the concentration of the hydrophilic polymer solution exceeds 20% by weight, the viscosity of the hydrophilic polymer solution may be too high to coat a uniform membrane, and a catheter such as a balloon catheter, a guide wire, There is a risk that it may be difficult to quickly cover the narrow and narrow inner surface of a medical device such as an indwelling needle. However, even if it is out of the above range, it can be sufficiently utilized as long as it does not affect the operational effects of the present invention.

When the dipping method (dipping method) is used, the dipping time in the hydrophilic polymer solution is not particularly limited, but is preferably 5 seconds to 30 minutes, more preferably 5 seconds to 5 minutes. Step of cross-linking a functional polymer>
In this step, the hydrophilic polymer that has been applied to the substrate is crosslinked to form a surface lubricating layer.

  The crosslinking temperature in this step is 10 ° C. or higher and lower than 100 ° C. When the crosslinking temperature is less than 10 ° C., the crosslinking reaction does not proceed efficiently, and a great deal of time is required until the crosslinking reaction is completed. On the other hand, when the temperature is 100 ° C. or higher, the base material may be deformed or melted. The crosslinking temperature is preferably 15 to 80 ° C, more preferably 20 to 60 ° C.

  The crosslinking time is not particularly limited, but is preferably 15 minutes to 30 hours, more preferably 30 minutes to 24 hours. When the crosslinking time is within the above range, the crosslinking reaction proceeds sufficiently, the amount of uncrosslinked hydrophilic polymer can be reduced, and the surface lubricity can be maintained for a long time. Moreover, it is advantageous also in terms of manufacturing cost.

  The pressure condition at the time of crosslinking is not limited at all, and it can be performed under normal pressure (atmospheric pressure), or under pressure or reduced pressure. In addition, when the reactive functional group of the hydrophilic polymer is an epoxy group, a reaction catalyst such as a trialkylamine compound or a tertiary amine compound such as pyridine is hydrophilic so that the crosslinking reaction can be promoted. The polymer solution may be added in an appropriate amount in a timely manner. In order to promote the crosslinking reaction, heating may be performed in a range of less than 100 ° C. In this case, as a heating means (device), for example, an oven, a dryer, a microwave heating device, or the like may be used. it can.

  Moreover, examples of the method for promoting the crosslinking reaction of the hydrophilic polymer other than the heat treatment include irradiation with light, electron beam, radiation and the like, but are not limited thereto.

  In the present specification, “the hydrophilic polymer is crosslinked” means that the hydrophilic polymer is not completely dissolved in the solvent. Specifically, it means that the solubility of the hydrophilic polymer in THF at 25 ° C. is 0.1% by weight or less.

  The thickness of the surface lubrication layer is sufficient as long as it can permanently exhibit excellent surface lubricity during use, and the thickness of the surface lubrication layer when not swollen is preferably 0. .5 to 5 μm, more preferably 1 to 5 μm, and still more preferably 1 to 3 μm. When the thickness of the non-swelled surface lubricating layer is less than 0.5 μm, it is difficult to form a uniform film, and the surface lubricating property may not be sufficiently exhibited when wet. On the other hand, when the thickness of the non-swelled surface lubricating layer exceeds 5 μm, the thick surface lubricating layer swells, so that when inserting the medical device into a blood vessel or the like in a living body, the blood vessel or the like When passing a portion having a small clearance from the device (for example, the inside of a peripheral blood vessel or the like), there is a possibility that the internal tissue such as the blood vessel is damaged or the medical device is difficult to pass.

  After the surface lubrication layer is formed, it is possible to wash the excess hydrophilic polymer with an appropriate solvent and leave only the hydrophilic polymer firmly fixed to the substrate.

  The surface lubrication layer thus formed absorbs physiological saline, buffer solution, blood, etc. at the temperature used (usually 30 to 40 ° C.) and exhibits lubricity.

[Use of medical devices]
Applications of the medical device of the present invention include those in which the surface has lubricity in an aqueous liquid such as body fluid or physiological saline, and the operability can be improved and damage to the tissue mucosa can be reduced. Specific examples include catheters such as balloon catheters used in blood vessels, guide wires, indwelling needles, and the like, and the following medical devices are also shown.

  (A) Catheters inserted or placed in the digestive organs orally or nasally, such as gastric tube catheters, nutritional catheters, tube feeding tubes and the like.

  (B) Oxygen catheters, oxygen canulas, endotracheal tube tubes and cuffs, tracheostomy tube tubes and cuffs, intratracheal suction catheters, and other catheters that are inserted or placed in the trachea or trachea orally.

  (C) Catheters inserted into or placed in the urethra or ureter, such as urethral catheters, urinary catheters, balloon catheters, and balloons.

  (D) Catheters that are inserted or placed in various body cavities, organs, and tissues such as suction catheters, drainage catheters, and rectal catheters.

  (E) Indwelling needles, IVH catheters, thermodilution catheters, angiographic catheters, catheters inserted or placed in blood vessels such as dilators or introducers, or guide wires and stylets for these catheters Such.

  (F) Examination and treatment instruments for inserting various organs, contact lenses, and the like.

  (G) Stents, artificial blood vessels, artificial trachea, artificial bronchi, etc.

  (H) Medical devices for extracorporeal circulation treatment (artificial lung, artificial heart, artificial kidney, etc.) and their circuits.

  The effects of the present invention will be described in further detail using the following examples and comparative examples. However, the technical scope of the present invention is not limited to the following examples.

Example 1
Nylon 12 (manufactured by ARKEMA Co., Ltd., RILSAN (registered trademark) AECNO TL) and polyamide elastomer (manufactured by EMS Chemie Japan Co., Ltd., Grillamide ELG6260) are mixed at 2: 8 (weight ratio), and a tube is produced by extrusion molding. did. The produced tube was immersed in a tetrahydrofuran (THF) solution containing soluble polyamide (manufactured by Fuji Kasei Kogyo Co., Ltd., TPAE-826) at a concentration of 10% by weight for 1 minute, and then dried in an oven at 50 ° C. for 2 hours. Next, a block having polydimethylacrylamide (DMAA) as a block formed from a hydrophilic monomer, and a block having polyglycidyl methacrylate (GMA) as a block formed from a monomer having a reactive functional group (epoxy group). The tube was immersed for 30 seconds in a THF solution in which a copolymer [p (DMAA-b-GMA)] (DMAA: GMA (molar ratio) = 12: 1) was dissolved at a concentration of 3.5% by weight. . Thereafter, the tube was air-dried for one day (left at 25 ° C. for 12 hours) to obtain a tube having a surface lubrication layer made of p (DMAA-b-GMA) coated on the surface.

(Comparative Example 1)
In Example 1, a surface lubrication layer made of p (DMAA-b-GMA) was coated on the surface in the same manner as in Example except that it was not immersed in a THF solution of 10% by weight of soluble polyamide. Tube was obtained.

<Surface lubrication evaluation>
About the tube produced in Example 1 and Comparative Example 1, the surface lubrication durability was evaluated by the following method using a friction measuring machine (manufactured by Trinity Labs, Handy Tribomaster TL201).

  That is, as shown in FIG. 1, a double-sided tape was affixed to a glass petri dish 2, and the tube 5 obtained in Example 1 and Comparative Example 1 was fixed to the adhesive surface. The petri dish 2 was filled with water 1 and placed on a friction measuring machine. And 300 g of load was applied to the spherical contactor 3 made from SUS with the weight 4, and the friction resistance value at the time of sliding 50 times repeatedly at a speed | rate of 750 mm / min was measured for the distance of 30 mm. At this time, measurement was performed with n = 2 for Example 1 and n = 3 for Comparative Example 1, and the measurement results are shown in the graph.

  FIG. 2 shows the measurement results of the surface lubricity maintenance of the tube produced in Example 1, and FIG. 3 shows the measurement results of the surface lubricity maintenance of the tube produced in Comparative Example 1. As a result of the measurement, Example 1 showed a substantially constant low frictional resistance value (test force). On the other hand, in Comparative Example 1, although the initial value showed a low frictional resistance value, the frictional resistance value increased due to peeling of the surface lubricating layer during repeated sliding, and the surface lubricating durability was poor.

1 water,
2 Petri dishes,
3 SUS spherical contact,
4 weights,
5 tubes.

Claims (6)

A substrate whose surface is at least partly polyamide;
An adhesive layer formed on the surface of the base material and containing polyamide dissolved in an organic solvent;
A surface comprising at least one reactive functional group selected from the group consisting of an epoxy group, an acid chloride group, and an isocyanate group and including a crosslinked hydrophilic polymer formed on the adhesive layer. A lubricating layer;
Including medical devices.   The medical device according to claim 1, wherein the polyamide dissolved in the organic solvent is non-crosslinked.   The medical device according to claim 1 or 2, wherein the hydrophilic polymer is a copolymer of a hydrophilic monomer and a monomer having a reactive functional group.   The medical device according to any one of claims 1 to 3, wherein the medical device is a catheter or a guide wire.   The medical device according to any one of claims 1 to 3, wherein the medical device is a balloon catheter. Applying and drying a solution containing polyamide that dissolves in an organic solvent on the surface of a base material, at least a part of which is polyamide; and
After the step of applying and drying, applying a solution containing a hydrophilic polymer having at least one reactive functional group selected from the group consisting of an epoxy group, an acid chloride group, and an isocyanate group;
Cross-linking the hydrophilic polymer at a temperature of 10 ° C. or more and less than 100 ° C .;
A method for manufacturing a medical device, comprising:

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