Medical device and method for manufacturing medical device

Abstract

Provided is a method for manufacturing a medical instrument having a surface lubricating layer that exhibits excellent durability. The present invention pertains to a method for manufacturing a medical instrument provided with a base material layer and a surface lubricating layer supported on at least a portion of the base material layer, the method comprising: preparing a coating liquid; the coating liquid contains a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, at least one polymer material selected from polyvinyl chloride and polyurethane, and a solvent. And a step for applying the coating liquid onto the base material layer.

Description

Technical Field

[0001] The present invention relates to a medical appliance and a method for manufacturing the medical appliance. Background Art

[0002] Medical devices (medical instruments) inserted into a living body, such as catheters, guidewires, and indwelling needles, are required to exhibit excellent lubricity in order to reduce damage to tissues such as blood vessels and improve operability for the operator. Therefore, a method of coating a substrate layer with lubricity with a hydrophilic polymer has been developed and put into practical use. In such medical devices, the dissolution and peeling of the hydrophilic polymer from the substrate layer surface is a problem in terms of maintaining safety and operability. Therefore, coatings formed from hydrophilic polymers are required not only to have excellent lubricity but also to be durable against loads such as wear and friction.

[0003] With this in mind, Japanese Patent Application Laid-Open No. 8-33704 discloses a medical device in which a water-soluble or water-swellable polymer is dissolved in a solvent that swells the substrate of the medical device to prepare a polymer solution. The substrate of the medical device is immersed in the polymer solution to swell it, and the polymer is then crosslinked or polymerized on the substrate surface, thereby forming a surface lubricating layer on the substrate surface. The technology disclosed in Japanese Patent Application Laid-Open No. 8-33704 makes it possible to attach a surface lubricating layer exhibiting relatively good lubricity to the substrate. Summary of the Invention

[0004] Japanese Patent Application Laid-Open No. 8-33704 discloses that, as a water-soluble or water-swellable polymer, it is preferred to use a block copolymer comprising a hydrophilic portion presenting lubricity and a portion having an epoxy group. Furthermore, if such a block copolymer is used, the epoxy group of the block copolymer can be cross-linked by a heating operation to form a surface lubricating layer that is less likely to be peeled off. However, there is a trade-off between good lubricity and excellent durability, requiring the technology to achieve good lubricity and excellent durability simultaneously.

[0005] In particular, the miniaturization and thinning of medical devices in recent years have been significant. In a living body, medical methods that pass medical devices through biological lumens such as blood vessels with higher curvature and narrower slits to reach the lesion site are becoming popular. In addition, as medical methods become more complicated, it is sometimes necessary to operate medical devices for a long time. Therefore, in order to maintain the operability of medical devices well even in complex lesions, a technology that further improves the lubrication maintenance (durability) of the surface (surface lubricating layer) of the medical device is required compared to the existing technology. More specifically, a device with excellent sliding durability that can maintain high lubricity even when the surface (surface lubricating layer) of the medical device is repeatedly slid is required.

[0006] Therefore, there is a demand for a technology that can improve the durability (particularly sliding durability) of medical devices and support increasingly complex and advanced medical procedures.

[0007] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a method for producing a medical device having a surface lubricating layer that exhibits excellent durability (lubrication retention) (particularly sliding durability).

[0008] The inventors of the present application conducted intensive studies to solve the above-mentioned problems and found that the above-mentioned object can be achieved by combining an electron-withdrawing polymer material with a hydrophilic block copolymer having epoxy groups, thereby completing the present invention.

[0009] The above-mentioned object can be achieved by the present invention having the following configuration, and the present invention includes the following aspects and configurations.

[0010] One embodiment of the present invention is as follows:

[0011] 1. A method for producing a medical device comprising a base layer and a surface lubricating layer carried on at least a portion of the base layer, the method comprising:

[0012] preparing a coating liquid comprising a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, a polymer material of at least one selected from polyvinyl chloride and polyurethane, and a solvent; and

[0013] The coating liquid is applied onto the substrate layer.

[0014] 2. In the production method described in 1. above, the content of the polymer material in the coating liquid is preferably smaller than the content of the block copolymer in the coating liquid.

[0015] 3. In the production method described in 1. or 2. above, the coating liquid preferably contains the polymer material in an amount of 0.001 mass % or more and less than 12 mass %.

[0016] 4. In the production method described in any one of 1. to 3. above, the reactive monomer having an epoxy group preferably includes at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether.

[0017] 5. In the production method according to any one of 1. to 4. above, the hydrophilic monomer preferably includes at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone.

[0018] Another embodiment of the present invention is as follows:

[0019] 6. A medical device comprising a base layer and a surface lubricating layer carried on at least a portion of the base layer.

[0020] The surface lubricating layer comprises: a block copolymer comprising a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer; and a polymer material selected from at least one of polyvinyl chloride and polyurethane.

[0021] In the surface lubricating layer, the block copolymer and the polymer material are entangled with each other.

[0022] 7. In the medical device according to 6. above, the amount of the polymer material present in the surface lubricating layer is preferably smaller than the amount of the block copolymer present in the surface lubricating layer.

[0023] 8. In the medical device according to 6. or 7. above, the reactive monomer having an epoxy group preferably comprises at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether.

[0024] 9. In the medical device according to any one of 6. to 8. above, the hydrophilic monomer preferably includes at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] [ Figure 1 ] is a partial cross-sectional view schematically showing the layered structure of the surface of a representative embodiment of the medical device according to the present invention. Figure 1 10 represents a medical device; 1 represents a base material layer; and 2 represents a lubricating layer.

[0026] [ Figure 2 ] is a schematic representation of Figure 1 A partial cross-sectional view of a configuration example in which the surface layer stacking configuration is different according to an application example of the embodiment. Figure 2 10 denotes a medical device; 1a denotes a core portion of a substrate layer; 1b denotes a substrate surface layer; and 2 denotes a lubricating layer. DETAILED DESCRIPTION

[0027] One embodiment of the present invention relates to a method for producing a medical device comprising a substrate layer and a surface lubricating layer supported on at least a portion of the substrate layer. The method comprises: preparing a coating liquid comprising a block copolymer comprising a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer; a polymer material comprising at least one selected from polyvinyl chloride and polyurethane; and a solvent; and applying the coating liquid to the substrate layer. According to the present invention, a medical device having a surface lubricating layer exhibiting excellent durability (lubrication retention), particularly sliding durability, can be produced.

[0028] In this specification, the structural unit (A) derived from a reactive monomer having an epoxy group is also referred to simply as "the structural unit (A) according to the present invention" or "structural unit (A)." In this specification, the structural unit (B) derived from a hydrophilic monomer is also referred to simply as "the structural unit (B) according to the present invention" or "structural unit (B)." In this specification, the block copolymer having structural units (A) and (B) is also referred to simply as "the block copolymer according to the present invention" or "block copolymer."

[0029] In this specification, at least one polymer material selected from polyvinyl chloride and polyurethane is also simply referred to as "the polymer material according to the present invention" or "polymer material".

[0030] In this specification, when a certain structural unit is defined as “derived from” a certain monomer, it means that the structural unit is a structural unit produced by cleaving one polymerizable unsaturated double bond possessed by the corresponding monomer.

[0031] In this specification, the term "(meth)acrylic acid" includes both acrylic acid and methacrylic acid. Thus, for example, the term "(meth)acrylic acid" includes both acrylic acid and methacrylic acid. Similarly, the term "(meth)acryloyl" includes both acryloyl and methacryloyl. Thus, for example, the term "(meth)acryloyl" includes both acryloyl and methacryloyl. Furthermore, similarly, the term "(meth)acrylate" includes both acrylate and methacrylate. For example, the term "alkoxyalkyl (meth)acrylate" includes both alkoxyalkyl acrylate and alkoxyalkyl methacrylate.

[0032] In this specification, "X to Y" indicating a range includes both X and Y, and means "X or more and Y or less." Furthermore, "X and / or Y" includes all combinations of X and Y, and specifically, means at least one of X and Y, including X alone, Y alone, and combinations of X and Y.

[0033] Unless otherwise specified, the operation and measurement of physical properties were carried out under the conditions of room temperature (20 to 25° C.) and relative humidity of 40 to 50% RH.

[0034] In the present invention, a coating liquid is prepared, and the coating liquid is applied to the substrate layer. The coating liquid includes a block copolymer having a structural unit (A) from a reactive monomer with an epoxy group and a structural unit (B) from a hydrophilic monomer, at least one of polyvinyl chloride and polyurethane (polymer material), and a solvent. That is, the present invention is characterized in that at least one of polyvinyl chloride and polyurethane (polymer material) and a block copolymer are used to form a surface lubricating layer. The polymer material to which the present invention relates has electron-withdrawing properties. Therefore, if the polymer material contacts the block copolymer, the electrons of the epoxy group (crosslinking portion) are stripped, the bond is cut, and the epoxy group is ring-opened. If the epoxy group is ring-opened, the crosslinking (bonding) of the block copolymers is carried out, and the film strength of the surface lubricating layer is improved. In addition, when the substrate layer is a resin material, the crosslinking (bonding) of the block copolymer and the substrate layer is also produced by utilizing the ring-opened epoxy group. The ring-opening reaction of the epoxy group is an electron transfer between molecules-molecules, so the polymer material and the block copolymer (hydrophilic polymer molecule) need to be close to the electron orbital overlap of the molecule. However, in the coating liquid, there is a solvent between the polymer material and the block copolymer, so the polymer material and the block copolymer will not be in close contact, but exist separately. Therefore, the polymer material will not attract the electronics of the epoxy group (crosslinking portion), and the ring opening (crosslinking reaction) of the epoxy group is almost or completely not carried out in the coating liquid. Since the coating liquid does not carry out the ring opening of the epoxy group of the block copolymer, the viscosity will not become high or gelation, and the form of the solution can be maintained. Therefore, the coating liquid can be evenly coated on the substrate layer. On the other hand, if after the coating liquid is applied on the substrate layer, the solvent is removed from the coating film of the coating liquid by heat drying, the polymer material contacts the block copolymer and attracts electrons (the electron orbits of the molecules overlap), and the ring opening (crosslinking reaction) of the epoxy group is initiated and promoted. According to the method of the present invention, the coating liquid can be evenly coated on the substrate layer, in addition, the ring opening (crosslinking reaction) of the epoxy group is evenly and tightly carried out on the substrate layer surface, so the film strength of the surface lubricating layer can be improved, and the block copolymer is more firmly fixed on the substrate layer surface. As a result, it is speculated that a surface lubricating layer (firm coating layer) with high film strength is formed, and the firm coating layer can be well maintained even after sliding in biological lumens such as relatively more flexible and narrow blood vessels, and high lubricity (surface lubricity) can be maintained for a longer period of time (i.e., excellent surface lubricity can be maintained and sliding durability can be improved). In particular, when the coating film of the coating liquid is heat-treated (heat energy is applied), the expansion and contraction of the molecules caused by the heat energy more actively causes the movement of electrons, further promoting the ring opening (cross-linking reaction) of the epoxy group, thereby further improving the durability of the surface lubricating layer. It should be noted that the above mechanism is speculation and does not limit the technical scope of the present invention.

[0035] Therefore, the medical device manufactured according to the method of the present invention has excellent durability (surface lubrication maintenance, sliding durability). In addition, the medical device manufactured according to the method of the present invention also has excellent lubricity.

[0036] The following describes the embodiments of the present invention. It should be noted that the present invention is not limited to the following embodiments, and various changes can be made within the scope of the claims. In addition, the embodiments described in this specification can be combined arbitrarily to form other embodiments. For the sake of convenience, the dimensional ratios of the drawings are exaggerated and sometimes differ from the actual ratios. In addition, with reference to the attached drawings, Figure 1 While describing the embodiments of the present invention, the same elements will be denoted by the same reference numerals in the description of the drawings, and redundant description will be omitted.

[0037] Throughout this specification, unless otherwise specified, expressions in the singular should be understood as also including the concept of its plural form. Therefore, unless otherwise specified, articles in the singular (for example, "a", "an", "the", etc. in the case of English) should be understood as also including the concept of its plural form. In addition, in this specification, unless otherwise specified, the terms used should be understood as being used in the sense commonly used in the art. Therefore, unless otherwise defined, all technical terms and scientific terms used in this specification have the same meaning as commonly understood by those skilled in the art in the field to which the invention belongs. In the event of a conflict, this specification (including definitions) takes precedence.

[0038] <Method for Manufacturing Medical Device>

[0039] The method for producing a medical device according to the present invention comprises: preparing a coating liquid ((I) preparation step) comprising a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, a polymer material of at least one selected from polyvinyl chloride and polyurethane, and a solvent; and applying the coating liquid onto the substrate layer ((II) coating step). By using a solution containing the block copolymer and the specific polymer material as the coating liquid, a medical device having a surface lubricating layer (coating layer) exhibiting excellent durability can be obtained.

[0040] After the above-mentioned step (II), as needed, further steps such as a step of drying and / or heat treatment ((III) drying / heat treatment step) and a step of cleaning ((IV) cleaning step) can be implemented. Among these, it is preferred to further carry out at least the (III) drying / heat treatment step after the above-mentioned step (II). It should be noted that, in the method of the present invention, the polymer material is stably maintained in the surface lubricating layer. In addition, the epoxy group of the block copolymer is ring-opened without the addition of acid or alkali. Therefore, in the method of the present invention, there is no need to particularly carry out the (IV) cleaning step, which is conducive to mass production.

[0041] (I) Preparation process

[0042] In this process, a coating liquid comprising a block copolymer, a polymer material, and a solvent is prepared. Here, in this process, a coating liquid can be prepared by mixing the block copolymer, the polymer material, and the solvent, thereby preparing the coating liquid. Alternatively, a coating liquid comprising a block copolymer, a polymer material, and a solvent can be purchased and used.

[0043] Hereinafter, a preferred embodiment will be described in detail regarding the case where a coating liquid is prepared by mixing a block copolymer, a polymer material, and a solvent to prepare the coating liquid.

[0044] (Block copolymer)

[0045] In the present invention, the block copolymer forms a surface lubricating layer supported on at least a portion of the substrate layer in a state of being entangled with the polymer material. That is, in the medical device obtained by the method of the present invention, the surface lubricating layer comprises the block copolymer and the polymer material. It should be noted that "supported" refers to a state in which the surface lubricating layer is immobilized in a state that is not easily freed from the surface of the substrate layer, and includes not only a state in which the entire surface of the substrate layer is completely covered by the surface lubricating layer, but also a state in which only a portion of the surface of the substrate layer is covered by the surface lubricating layer, that is, a state in which the surface lubricating layer is attached to only a portion of the surface of the substrate layer.

[0046] The block copolymer according to the present invention comprises a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer.

[0047] The reactive monomer having an epoxy group constituting the block copolymer has an epoxy group as a reactive group. By introducing the structural unit (A) derived from such a reactive monomer into the block copolymer, the epoxy group ring-opens and the block copolymers cross-link (bond) with each other, thereby improving the film strength of the surface lubricating layer. In addition, when the substrate layer is a resin material, the ring-opened epoxy group also causes cross-linking (bonding) between the block copolymer and the substrate layer.

[0048] The reactive monomer constituting the block copolymer is not particularly limited as long as it has an epoxy group (preferably a glycidyl group), and known compounds can be used. Wherein, from the perspective of easily controlling the crosslinking or polymerization of the block copolymer, the reactive monomer with an epoxy group preferably includes at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate (GMA), 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methyl glycidyl methacrylate, and allyl glycidyl ether. Wherein, in view of being able to further promote the crosslinking reaction, the ease of manufacture, etc., glycidyl (meth) acrylate is more preferred, and glycidyl methacrylate is particularly preferred.

[0049] The reactive monomers can be used alone or in combination of two or more. That is, the reactive site from the reactive monomer can be a homopolymer type consisting of a single reactive monomer, or a copolymer type consisting of two or more reactive monomers. It should be noted that the form of the reactive site when using two or more can be a block copolymer (block shape) or a random copolymer (random shape).

[0050] That is, in a preferred embodiment of the present invention, the reactive monomer having an epoxy group includes at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether. In a more preferred embodiment of the present invention, the reactive monomer having an epoxy group is at least one of glycidyl acrylate and glycidyl methacrylate. In a particularly preferred embodiment of the present invention, the reactive monomer having an epoxy group is glycidyl methacrylate.

[0051] The hydrophilic monomers that constitute the block copolymer swell when in contact with body fluids (e.g., blood, urine) or aqueous solvents, thereby imparting lubricity (surface lubricity) to the medical device. Therefore, by incorporating structural units (B) derived from such hydrophilic monomers into the block copolymer, the lubricity (surface lubricity) of the medical device is improved, thereby reducing friction when the medical device contacts a lumen wall such as a blood vessel wall.

[0052] The hydrophilic monomer constituting the block copolymer is not particularly limited as long as it has the above-mentioned properties, and known compounds can be used. Examples include acrylamide or its derivatives, vinyl pyrrolidone, acrylic acid or methacrylic acid and their derivatives, polyethylene glycol acrylate and its derivatives, monomers having sugars or phospholipids as side chains, and water-soluble monomers such as maleic anhydride. More specifically, acrylic acid, methacrylic acid, N-methylacrylamide, N,N-dimethylacrylamide (DMAA), acrylamide, acryloylmorpholine, N,N-dimethylaminoethyl acrylate, N-vinylpyrrolidone, 2-methacryloyloxyethyl phosphorylcholine, 2-methacryloyloxyethyl-D-glucoside, 2-methacryloyloxyethyl-D-mannoside, vinyl methyl ether, 2-hydroxyethyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 6-hydroxyhexyl (meth)acrylate, 1,4-cyclohexanedimethanol mono(meth)acrylate, (meth)acrylic acid ester, 2-hydroxyethyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 6-hydroxyhexyl (meth)acrylate, 1,4-cyclohexanedimethanol mono(meth)acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 6-hydroxyhexyl (meth)acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 6-hydroxyhexyl (meth)acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 6-hydroxyhexyl (meth)acrylate, 2-hydroxyethyl (meth)acrylate, 2-hydroxybutyl ...ethyl (meth 1-chloro-2-hydroxypropyl acrylate, diethylene glycol mono(meth)acrylate, 1,6-hexanediol mono(meth)acrylate, pentaerythritol tri(meth)acrylate, dipentaerythritol penta(meth)acrylate, neopentyl glycol mono(meth)acrylate, trimethylolpropane di(meth)acrylate, trimethylolethane di(meth)acrylate, 2-hydroxy-3-phenyloxypropyl (meth)acrylate, 4-hydroxycyclohexyl (meth)acrylate, 2-hydroxy-3-phenyloxy (meth)acrylate, 4-hydroxycyclohexyl (meth)acrylate, cyclohexanedimethanol mono(meth)acrylate, poly(ethylene glycol) methyl ether acrylate, and poly(ethylene glycol) methyl ether methacrylate. From the perspectives of imparting excellent lubricity, ease of synthesis, and ease of handling, the hydrophilic monomer preferably comprises at least one member selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone, and more preferably comprises at least one member selected from the group consisting of N,N-dimethylacrylamide, acrylamide, and 2-hydroxyethyl methacrylate. Among these, N,N-dimethylacrylamide is particularly preferred as the hydrophilic monomer from the perspective of excellent lubricity.

[0053] The above-mentioned hydrophilic monomers can be used alone or in combination of two or more. That is, the hydrophilic portion from the hydrophilic monomer can be a homopolymer type composed of a single hydrophilic monomer, or a copolymer type composed of two or more of the above-mentioned hydrophilic monomers. It should be noted that the form of the hydrophilic portion when using two or more types can be a block copolymer (block shape) or a random copolymer (random shape).

[0054] That is, in a preferred embodiment of the present invention, the hydrophilic monomer comprises at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinyl pyrrolidone. In a more preferred embodiment of the present invention, the hydrophilic monomer is at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, and 2-hydroxyethyl methacrylate. In a particularly preferred embodiment of the present invention, the hydrophilic monomer is N,N-dimethylacrylamide.

[0055] The block copolymer has the above-mentioned structural unit (A) and structural unit (B). Here, the ratio of structural unit (A) to structural unit (B) is not particularly limited as long as the above-mentioned effect is exerted. Taking into account good lubricity, lubrication maintenance, coating layer strength, bonding with the substrate layer, etc., the ratio of structural unit (A) to structural unit (B) (molar ratio of structural unit (A): structural unit (B)) is preferably 1:2 to 1:100, more preferably 1:2 to 1:50, further preferably 1:5 to 1:50, and particularly preferably 1:10 to 1:30. If it is within such a range, the surface lubricating layer can fully exert lubricity by utilizing the structural unit (B), and can also exert sufficient coating layer strength, bonding with the substrate layer (in the case of resin material) and durability by utilizing the structural unit (A). It should be noted that the molar ratio of the above-mentioned structural unit (A): structural unit (B) can be controlled by adjusting the charging ratio (molar ratio) of each monomer during the production stage of the block copolymer. Therefore, the charge ratio (molar ratio) of the reactive monomer having an epoxy group to the hydrophilic monomer in the production stage of the block copolymer is preferably 1:2 to 1:100, more preferably 1:2 to 1:50, further preferably 1:5 to 1:50, and particularly preferably 1:10 to 1:30. It should be noted that the molar ratio of the structural unit (A): the structural unit (B) can be determined, for example, by NMR measurement of the copolymer ( 1 H-NMR determination, 13 C-NMR measurement, etc.) to confirm.

[0056] The block copolymer to which the present invention relates must include structural unit (A) and structural unit (B), and in addition to these structural units, it may also have other structural units. As other structural units when the block copolymer has other structural units, adipic acid, glutaric acid, triethylene glycol and tripropylene glycol etc. can be enumerated. The monomer constituting other structural units can be used alone or in combination of two or more. That is, other structural units can be a homopolymer type consisting of a single structural unit, or a copolymer type consisting of two or more structural units. It should be noted that, when using two or more monomers constituting the above-mentioned other structural units, the section consisting of the monomer can be the form of a block copolymer, the form of a random copolymer, or the form of an alternating copolymer.

[0057] The content of other structural units when the block copolymer to which the present invention relates has other structural units is preferably more than 0 mol% and less than 5 mol% relative to the total structural units constituting the block copolymer. That is, in the block copolymer to which the present invention relates, when the total of the total structural units constituting the block copolymer is set to 100 mol%, the total of the content of structural unit (A) and structural unit (B) is preferably more than 95 mol% (upper limit: less than 100 mol%). More preferably, the block copolymer to which the present invention relates is substantially composed of structural unit (A) and structural unit (B) (the content of other structural units = more than 0 mol% and less than 5 mol%). If it is this form, the block copolymer to which the present invention relates can well realize the durability brought by structural unit (A) and the lubricity (surface lubricity) brought by structural unit (B) in a balanced manner. Preferably, the block copolymer to which the present invention relates does not include above-mentioned other structural units (content = 0 mol% of other structural units).

[0058] It should be noted that the composition of each structural unit (structural unit (A) and (B), other structural units) can be determined by a known method. For example, by measuring the composition of the block copolymer solution. 1 The composition (molar ratio) of the structural units can be determined by measuring the integrated ratio of each signal intensity of the H-NMR spectrum.

[0059] In one embodiment of the present invention, the block copolymer of the present invention is essentially composed of: a structural unit (A) derived from at least one reactive monomer selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether; and a structural unit (B) derived from at least one hydrophilic monomer selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone, or is composed solely of the structural units (A) and (B).

[0060] In one embodiment of the present invention, the block copolymer of the present invention is essentially composed of: a structural unit (A) derived from at least one reactive monomer selected from glycidyl acrylate and glycidyl methacrylate; and a structural unit (B) derived from at least one hydrophilic monomer selected from the group consisting of N,N-dimethylacrylamide, acrylamide, and 2-hydroxyethyl methacrylate, or is composed only of the structural unit (A) and the structural unit (B).

[0061] In one embodiment of the present invention, the block copolymer of the present invention is essentially composed of a structural unit (A) derived from glycidyl methacrylate (a reactive monomer having an epoxy group) and a structural unit (B) derived from N,N-dimethylacrylamide (a hydrophilic monomer), or is composed solely of the above.

[0062] From the perspective of solubility, the weight average molecular weight of the block copolymer is preferably 10,000 to 10,000,000. From the perspective of ease of preparation of the coating solution, the weight average molecular weight of the block copolymer is more preferably 100,000 to 5,000,000. In this specification, the "weight average molecular weight" is the value measured by gel permeation chromatography (GPC) using polystyrene as a standard substance.

[0063] The manufacture method of block copolymer is not particularly limited, for example, can apply living radical polymerization, the polymerization method using macromolecular initiator, polycondensation method etc. known in the past to make.Among these, from easily controlling the structural unit (position) from reactive monomer, the molecular weight and molecular weight distribution such aspect of the structural unit (position) from hydrophilic monomer are considered, can preferably utilize living radical polymerization or the polymerization method using macromolecular initiator.As living radical polymerization, there is no particular limit, for example, the method of recording in Japanese Patent Laid-Open No. 11-263819 Gazette, Japanese Patent Laid-Open No. 2002-145971 Gazette, Japanese Patent Laid-Open No. 2006-316169 Gazette etc. and atom transfer radical polymerization (ATRP) method etc. can be applied in the same manner or suitably modified rear application. In addition, in the polymerization method using a macroinitiator, for example, after preparing a macroinitiator containing a reactive site having a reactive functional group and a radical polymerizable group such as a peroxide group, the macroinitiator is polymerized with a monomer for forming a hydrophilic site, thereby producing a block copolymer having a hydrophilic site and a reactive site.

[0064] The block copolymer after polymerization is preferably purified by a common purification method such as reprecipitation, dialysis, ultrafiltration, or extraction.

[0065] (Polymer materials)

[0066] In the present invention, the polymer material comprises at least one selected from polyvinyl chloride and polyurethane. The polymer material has electron-withdrawing property. Therefore, if the polymer material contacts the block copolymer, the electrons of the epoxy group (crosslinking portion) of the block copolymer are stripped off, thereby inducing the ring opening of the epoxy group. The epoxy group ring is opened, and the crosslinking (bonding) of the block copolymers is carried out, and the film strength of the surface lubricating layer is improved. In addition, when the substrate layer is a resin material, the crosslinking (bonding) of the block copolymer and the substrate layer is also produced by utilizing the epoxy group of the ring opening. Therefore, for obtaining medical appliances by the method according to the present invention, durability (sliding durability) can be further improved, and in addition, its shape can also be well maintained after sliding. In addition, since polymer materials (polyvinyl chloride, polyurethane) have been used as medical materials, they are suitable in terms of safety.

[0067] The promotion of crosslinking of the block copolymers mentioned above can also be produced by adding acid or alkali to the coating liquid. However, in such a case, by the acid or alkali present in the coating liquid, the crosslinking or polymerization of the block copolymers in the coating liquid is rapidly carried out, and the viscosity of the coating liquid becomes high (or gelation), and it is sometimes difficult to apply evenly. In contrast, the contact of the polymer material with the block copolymer in the coating liquid is hindered by the solvent, so in the coating liquid, the crosslinking or polymerization of the block copolymers is not easy to proceed. In addition, the polymer material removes the solvent by heat drying, etc., and promotes the crosslinking reaction when in contact with the block copolymer. Therefore, the viscosity rise (gelation) of the coating liquid caused by the crosslinking of the block copolymers in the coating liquid mentioned above can be suppressed. Therefore, according to the method of the present invention, the coating liquid can be evenly coated on the substrate layer. In addition, when adding acid or alkali to the coating liquid, after forming the surface lubricating layer, it is necessary to remove the acid or alkali remaining in the surface lubricating layer from the cleaning process or to neutralize the acid or alkali remaining in the surface lubricating layer. In contrast, the method of the present invention does not require the above-mentioned additional steps, and thus can improve work efficiency.

[0068] In this specification, "electron-withdrawing property" refers to a property of easily attracting electrons from the atom to which it is bonded compared to a hydrogen atom.

[0069] The polymer material of the present invention comprises at least one of polyvinyl chloride and polyurethane. Among these, the electron-withdrawing property of polyvinyl chloride is higher, and therefore the crosslinking (which can further improve durability) brought about by the structural unit (A) of the block copolymer (especially during heat treatment) can be further promoted. In addition, the solvent solubility of polyvinyl chloride is higher (excellent coating property). Therefore, the polymer material preferably comprises at least polyvinyl chloride, and more preferably only polyvinyl chloride.

[0070] The weight average molecular weight (Mw) of the polymer material is 1,000 or more. From the perspective of solubility, the weight average molecular weight of the polymer material is preferably 500,000 or less. In addition, from the perspective of cross-linking promotion and stability, the weight average molecular weight of the polymer material is preferably 10,000 or more. As an example, the weight average molecular weight (Mw) of the polymer material is 1,000 to 10,000,000, preferably 10,000 to 500,000.

[0071] (Preparation of coating solution)

[0072] Coating liquid is prepared using the above-mentioned block copolymer, polymer material and solvent.Here, because polymer material is stable in coating liquid, it is preferred from the aspect of safety and simplicity of operation.In addition, in coating liquid, there is solvent between polymer material and block copolymer, and polymer material and block copolymer do not contact closely, but exist separately.On the other hand, by overlapping the electron orbits of the molecules close to block copolymer and polymer material, the exchange of electrons is carried out, thus starting and carrying out the ring opening (cross-linking reaction) of epoxy group.Therefore, in coating liquid, the ring opening (cross-linking reaction) of epoxy group is almost or not carried out completely, and the viscosity of coating liquid does not change almost or completely.Therefore, workability is excellent.

[0073] The order and method of adding the block copolymer, polymer material and solvent are not particularly limited. Each of the above components can be added at once, or separately in stages or continuously. In addition, the mixing method is also not particularly limited, and known methods can be used. As the preparation method of the coating liquid, there are methods of sequentially adding polymer material and block copolymer to a solvent, methods of sequentially adding block copolymer and polymer material to a solvent, or methods of disposable adding polymer material and block copolymer to a solvent, etc. Preferably, polymer material and block copolymer are sequentially added to a solvent, or block copolymer and polymer material are sequentially added to a solvent. In addition, if necessary, the above additions can be carried out while stirring. Alternatively, the mixed solution can be stirred after the above additions.

[0074] The solvent used in the preparation of the coating liquid is not particularly limited as long as it can dissolve the block copolymer, the polymer material (and in the case of using other components, other components), and is appropriately selected according to the type of the block copolymer, the polymer material (and in the case of using other components, other components). From the viewpoint of high solubility, it is preferred to use: alcohol solvents such as methanol, ethanol, isopropanol, butanol; organic solvents such as dichloromethane, chloroform, carbon tetrachloride, tetrahydrofuran (THF), dimethyl sulfoxide, N, N-dimethylformamide (DMF), dioxane, benzene, etc. These can be used alone or in combination of two or more (in the form of a mixed solvent).

[0075] The concentration of the block copolymer in the coating liquid is not particularly limited. From the viewpoint of further improving the lubricity and durability of the coating property, the concentration of the block copolymer in the coating liquid is preferably 0.5 to 20 mass %, more preferably 1 to 15 mass %, particularly preferably 3 to 10 mass %. When the concentration of the block copolymer is within the above range, the lubricity and durability of the resulting surface lubrication layer can be fully utilized. In addition, the uniform surface lubrication layer of the desired thickness can be easily obtained by 1 coating. In addition, the viscosity of the solution is within the appropriate range, and is preferably considered from the perspective of operability (for example, ease of coating), production efficiency. However, even if it exceeds the above range, as long as it does not affect the effect of the present invention, it can be fully utilized.

[0076] The concentration of the polymer material in the coating liquid is also not particularly limited. From the viewpoint of the lubricity (sliding property) of the surface lubricating layer, the less the addition of the polymer material, the more preferred. On the other hand, from the viewpoint of the durability (sliding durability) of the surface lubricating layer, it is preferred to add the polymer material to a certain extent. From the above-mentioned aspects, the concentration of the polymer material in the coating liquid is preferably 0.001 mass % or more and less than 12 mass %, more preferably 0.005 mass % or more and less than 4.0 mass %, further preferably 0.01 mass % or more and less than 0.5 mass %, particularly preferably 0.01 to 0.1 mass %. When the concentration of the polymer material is within the above-mentioned range, the lubricity (sliding property) of the surface lubricating layer is fully ensured, and the crosslinking of the block copolymer is fully carried out without excessively (crosslinking can be appropriately promoted). Therefore, the lubricity and durability of the obtained surface lubricating layer can be fully utilized. However, even if it exceeds the above-mentioned range, as long as it does not affect the effect of the present invention, it can be fully utilized.

[0077] In addition, with regard to the mixing ratio of the block copolymer and the polymer material in the coating liquid, from the viewpoint of further improving durability (sliding durability), coating properties, lubricity of the surface lubricating layer, etc., the content of the polymer material in the coating liquid is preferably less than the content of the block copolymer in the coating liquid. From the viewpoint of further improving durability (sliding durability), the content of the polymer material in the coating liquid is more preferably less than the content of the aforementioned block copolymer in the coating liquid. More specifically, the mixing ratio of the block copolymer and the polymer material in the coating liquid (block copolymer:polymer material (mass ratio)) is, for example, 100:0.01 or more and 100:100 or less, preferably 100:0.02 or more and less than 100:100, more preferably 100:0.1 or more and less than 100:90, further preferably greater than 100:0.1 and less than 100:70, further preferably greater than 100:0.15 and less than 100:50, particularly preferably greater than 100:0.2 and less than 100:10, and most preferably greater than 100:0.20 and less than 100:3.0. When the mass ratio of the block copolymer to the polymer material is within the above range, the durability and lubricity of the resulting surface lubricating layer can be fully exerted.

[0078] (Other ingredients)

[0079] The coating liquid for forming the surface lubricating layer may also include other components in addition to comprising block copolymers, polymer materials, and solvents. As other components, there are no particular restrictions. For example, when the purpose of medical appliances is to insert a catheter into a body cavity or a lumen, anticancer agents, immunosuppressants, antibiotics, antirheumatic drugs, antithrombotic drugs, HMG-CoA reductase inhibitors, ACE inhibitors, calcium antagonists, antihyperlipidemic drugs, integrin inhibitors, antiallergic agents, antioxidants, GPIIb / IIIa antagonists, retinoic acid, flavonoids, carotenoids, lipid-improving drugs, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet drugs, vascular smooth muscle proliferation inhibitors, anti-inflammatory drugs, materials derived from organisms, interferon, and NO produce agents (physiologically active substances) such as promoting substances. Here, the addition of other components is not particularly limited, and the amount commonly used can be applied in the same manner. The addition of other components can be considered to be the severity of the disease to be applied, the weight of the patient, etc. and finally appropriately selected.

[0080] (II) Coating process

[0081] In this step, the coating liquid prepared in the above-mentioned (I) preparation step is applied onto the base material layer to form a coating film (coating layer) on the base material layer.

[0082] The base material layer may be made of any material, and examples thereof include metal materials, polymer materials (resin materials), and ceramics.

[0083] In the material constituting the substrate layer, as metallic material, there is no particular restriction, can use the metallic material normally used in the medical appliances such as conduit, guide wire, indwelling needle.Specifically, can enumerate the various stainless steels such as SUS304, SUS314, SUS316, SUS316L, SUS420J2, SUS630, gold, platinum, silver, copper, nickel, cobalt, titanium, iron, aluminium, tin or the various alloys such as nickel-titanium alloy, nickel-cobalt alloy, cobalt-chromium alloy, zinc-tungsten alloy etc.These can be used alone a kind of, also can use two or more.In the above-mentioned metallic material, suitably select the best metallic material for the substrate layer as the conduit, guide wire, indwelling needle etc. of use.

[0084] In addition, in the material constituting above-mentioned substrate layer, as polymeric material (resin material or elastomeric material), there is no particular restriction, can use normally used polymeric material in the medical appliances such as conduit, intubation device, guide wire, indwelling needle.Specifically, can enumerate the polyolefin resins such as polyamide resin, polyethylene resin, polypropylene resin, modified polyolefin resin, cyclic polyolefin resin, epoxy resin, polyurethane resin, diallyl phthalate resin (allyl resin), polycarbonate resin, fluororesin, amino resin (urea resin, melamine resin, benzoguanamine resin), polyethylene terephthalate resin, polyester resins such as polybutylene terephthalate resin, styrene resin, acrylic resin, polyacetal resin, vinyl acetate resin, phenolic resin, vinyl chloride resin, silicone resin (silicone resin), polyether resin, polyimide resin etc.

[0085] Furthermore, thermoplastic elastomers such as polyurethane elastomer, polyester elastomer, and polyamide elastomer (nylon elastomer) can also be used as the material of the base material layer.

[0086] These polymer materials can be used alone as one, or as a mixture of more than two or more monomers constituting any one of the above-mentioned resins or elastomers. Wherein, as polymer material, preferably polyethylene resin, polyurethane resin, polyethylene terephthalate resin, polyamide resin, polyamide elastomer, more preferably polyamide resin, polyamide elastomer. As the carboxyl group and amino group of the terminal group contained in polyamide resin and polyamide elastomer, cross-linking reaction can be carried out with the epoxy group in block copolymer. In addition, these polymer materials (especially polyamide resin and polyamide elastomer) are softer, and it can be said that the block copolymer constituting the surface lubricating layer is easy to penetrate. Therefore, the bonding property of polymer material (especially polyamide resin and polyamide elastomer) and block copolymer is improved, and a surface lubricating layer with more excellent durability can be formed. Among the above-mentioned polymer materials, it is appropriate to select the best polymer material for the base material layer of the catheter, guide wire, indwelling needle etc. as the use purpose.

[0087] The shape of the base material layer is not particularly limited and may be a sheet, a wire, a rod, a tube, or the like, and may be appropriately selected depending on the intended use.

[0088] The method for applying the coating liquid to the surface of the substrate layer is not particularly limited, and conventionally known methods such as coating and printing, dipping (dipping method, dip coating), spraying, spin coating, mixed solution impregnation sponge coating, rod coating, die coating, reverse coating, comma coating, gravure coating, and knife coating can be applied. Among these, dipping (dipping method, dip coating) is preferably used.

[0089] It should be noted that when forming a surface lubricating layer on the narrow inner surface of a catheter, guidewire, injection needle, etc., the base layer can be immersed in the coating liquid and the system can be decompressed to degas. Decompression and degassing allow the solution to quickly penetrate the narrow inner surface, promoting the formation of the surface lubricating layer.

[0090] When forming the surface lubricating layer only on a portion of the base layer, the surface lubricating layer can be formed on a desired surface portion of the base layer by immersing only a portion of the base layer in the coating liquid and then applying the coating liquid to the portion of the base layer.

[0091] When it is difficult to immerse only a part of the substrate layer in the coating liquid, the surface portion of the substrate layer that does not need to form a surface lubricating layer is protected (coated, etc.) in advance with a suitable detachable (installation and disassembly) member or material, and then the substrate layer is immersed in the coating liquid, the coating liquid is applied to the substrate layer, and then the protective member (material) of the surface portion of the substrate layer that does not need to form a surface lubricating layer is removed, and then reacted by heat treatment, etc., thereby forming a surface lubricating layer at the desired surface portion of the substrate layer. However, in the present invention, it is not subject to any restrictions of these formation methods, and a surface lubricating layer can be formed using a method known in the past. For example, when it is difficult to immerse only a part of the substrate layer in the coating liquid, other coating methods (for example, using a coating device such as a spray device, a rod coater, a die coater, a reverse coater, a comma coater, a gravure coater, a spray coater, a scraper, etc., to apply the coating liquid to a prescribed surface portion of the medical appliance) can be used instead of the dipping method. It should be noted that, in terms of the structure of medical devices, when both the outer and inner surfaces of a cylindrical device need to have a surface lubricating layer, it is preferable to use a dipping method (impregnation method) from the perspective of being able to coat both the outer and inner surfaces at one time.

[0092] The coating amount of the coating liquid is preferably such that the thickness (dry film thickness) of the resulting film (surface lubricating layer) is 0.1 to 10 μm, more preferably such that the thickness (dry film thickness) of the resulting film (surface lubricating layer) is 0.5 to 5 μm, and even more preferably such that the thickness (dry film thickness) of the resulting film (surface lubricating layer) is 1 to 3 μm. When the coating amount is such that the thickness of the film (surface lubricating layer) is 0.1 μm or more, the durability of the resulting film (surface lubricating layer) can be fully achieved. In addition, when the coating amount is such that the thickness of the film (surface lubricating layer) is 10 μm or less, the surface of the film (surface lubricating layer) becomes less sticky, and handling during production becomes easier.

[0093] (III) Drying / Heat Treatment Step

[0094] In the method for manufacturing a medical device according to the present invention, a drying step and / or a heat treatment step may be performed, if necessary, after the coating liquid is applied to the substrate layer to form a coating film (coating layer) in the coating step (II). For the purpose of removing the solvent and forming a strong surface lubricating layer, the drying step and / or the heat treatment step are preferably performed, and the drying step and the heat treatment step are more preferably performed.

[0095] Here, "drying treatment" and "heating treatment" are not strictly distinguished. For the sake of convenience, the so-called "drying treatment" refers to keeping the substrate layer coated with the above-mentioned coating liquid at a temperature near room temperature (20-30°C) or below, and the so-called "heating treatment" refers to keeping the temperature above room temperature (20-30°C).

[0096] The conditions for drying or heat treatment are not particularly limited as long as a surface lubricating layer containing a block copolymer can be formed on the base layer.

[0097] The temperature of drying or heat treatment is not particularly limited, and is preferably 10 to 200° C. That is, it is more preferred that the coating layer be maintained at 10 to 200° C. after the block copolymer solution is applied to the substrate layer (after forming the coating layer). By maintaining at such a temperature, the crosslinking or polymerization of the block copolymer can be effectively promoted to form a firm coating layer (surface lubricating layer). Therefore, high lubricity (surface lubricity) can be maintained for a longer period of time. In addition, by maintaining at such a temperature, it is possible to suppress the above-mentioned crosslinking or polymerization from being excessively carried out. Therefore, the reduction in swelling caused by the surface lubricating layer becoming too hard can be suppressed, and as a result, good lubricity (surface lubricity) can be maintained.

[0098] In addition, it is more preferred that after the block copolymer solution is applied to the substrate layer (after forming the coating layer), the coating layer is maintained at 200°C or less, further preferably at 20 to 150°C, and most preferably at 50 to 130°C. By maintaining it at such a temperature, the cross-linking reaction is further promoted, and a surface lubricating layer with higher durability can be formed. In addition, the surface lubricating layer can exert excellent lubricity. In particular, by making it below 150°C, it is possible to suppress excessive cross-linking or polymerization of the block copolymer. In addition, it is possible to prevent and suppress the reduction in the hydrophilicity of the structural unit (B) of the block copolymer. Therefore, it is possible to suppress the reduction in swelling caused by the surface lubricating layer becoming too hard, and it is possible to more easily control the lubricity. It should be noted that the above-mentioned temperature can be changed in the middle of the drying or heat treatment.

[0099] In addition, the time for drying or heat treatment is not particularly limited, and is preferably 30 minutes to 30 hours, more preferably 1 to 25 hours, and particularly preferably 1 to 12 hours. By making it such a time, the crosslinking or polymerization in the block copolymer can be effectively promoted to form a strong coating layer (surface lubricating layer). Therefore, high lubricity (surface lubricity) can be maintained for a longer time. In addition, by making it such a time, it is possible to suppress the excessive crosslinking or polymerization of the above-mentioned. Therefore, the reduction in swelling caused by the surface lubricating layer becoming too hard can be suppressed, and as a result, good lubricity (surface lubricity) can be maintained. In particular, by making the heat treatment time 25 hours (especially 15 hours or 12 hours) or less, it is possible to prevent and suppress the reduction in the hydrophilicity of the structural unit (B) of the block copolymer, and it is possible to more easily control lubricity. It should be noted that when the substrate layer is composed of the above-mentioned polymer material (resin material or elastomeric material), the time for drying or heat treatment can be a shorter time, for example, 15 minutes to 5 hours, 30 minutes to 3 hours or so. If it is such a short time, the damage to the hydrophilic groups in the structural unit (B) (reduction in the hydrophilicity of the structural unit (B) of the block copolymer) can be further suppressed, so the surface lubricating layer can exert better lubricity. In addition, there is an advantage that even polymer materials that are easily deformed or plasticized by heat can be used as the substrate layer. Therefore, according to the present invention, the selectivity of the material becomes wider, and medical appliances for various purposes can be manufactured. In addition, since a surface lubricating layer with excellent durability can be formed at low temperatures, it is also preferred from the perspective of energy cost when manufacturing medical appliances.

[0100] In this process, from the viewpoint of particularly effectively (efficiently) promoting crosslinking or polymerization of block copolymer, it is preferably further heat-treated after drying.Thus, by via drying and heat-treated, thus further heat-treated under the state where solvent is evaporated away (that is, under the state where block copolymer and polymer material are easily contacted), it is possible to further improve the crosslinking or polymerization effect of the promotion block copolymer brought by polymer material.In addition, heat-treated can be made to be carried out in a shorter time, even if it is easily deformed or plasticized by heat, it is possible to use it as substrate layer.

[0101] The conditions for drying and heating treatment (temperature, time, etc.) at this time are not particularly limited. From the perspective of efficiently manufacturing medical devices, when the substrate layer is composed of a polymer material, it is preferred to perform a drying treatment at 10 to 30°C for 15 minutes to 5 hours and then perform a heat treatment at 40 to 200°C for 30 minutes to 10 hours. Furthermore, from the same perspective, it is more preferred to perform a drying treatment at 15 to 30°C for 30 minutes to 3 hours and then perform a heat treatment at 45 to 150°C for 1 to 6 hours. It is particularly preferred to perform a drying treatment at 20 to 25°C for 30 minutes to 1.5 hours and then perform a heat treatment at 50 to 130°C for 1 to 3 hours. From the same perspective, when the substrate layer is composed of a metal material, it is preferred to perform a drying treatment at 10 to 30°C for 15 minutes to 5 hours and then perform a heat treatment at 40 to 200°C for 5 to 20 hours. From the same perspective, it is more preferable to perform a drying treatment at 15-30°C for 30 minutes to 3 hours followed by a heat treatment at 80-150°C for 8-18 hours. It is particularly preferable to perform a drying treatment at 20-25°C for 30 minutes to 1.5 hours followed by a heat treatment at 100-130°C for 10-15 hours. These conditions allow the production of medical devices with a surface lubricating layer having excellent durability. It should be noted that the heat treatment may be followed by a drying treatment.

[0102] Under the above-mentioned conditions (temperature, time, etc.), a strong surface lubricating layer (coating layer) can be supported on the surface of the substrate layer. Furthermore, depending on the type of substrate layer, a cross-linking reaction can occur via the epoxy groups in the block copolymer in the surface lubricating layer, forming a high-strength surface lubricating layer that is not easily peeled off from the substrate layer. Therefore, the above-mentioned drying / heating treatment steps can effectively suppress and prevent the surface lubricating layer from peeling off from the substrate layer.

[0103] Furthermore, the pressure conditions during drying are not particularly limited, and the drying may be carried out under normal pressure (atmospheric pressure), increased pressure, or reduced pressure.

[0104] As the drying or heating means (device), for example, an oven, a reduced pressure dryer, etc. can be used, but in the case of natural drying, no special drying means (device) is required.

[0105] <Medical Equipment>

[0106] By going through the (I) preparation step and the (II) coating step described above, and the (III) drying / heat treatment step as required, a medical device having a surface lubricating layer (coating layer) exhibiting excellent durability can be produced.

[0107] Specifically, according to the method of the present invention, by forming a coating layer comprising a block copolymer and a polymer material on the surface of a substrate layer and then crosslinking the epoxy groups, a strong surface lubricating layer that does not easily peel from the substrate layer can be formed. Furthermore, the medical device obtained by the method of the present invention has a surface lubricating layer formed on the surface using the block copolymer, thereby exhibiting excellent lubricity and durability (lubricity retention).

[0108] The medical device manufactured by the method of the present invention has the following structure: a coating liquid containing a block copolymer and a polymeric material forming a surface lubricating layer is applied to a substrate layer, thereby supporting the surface lubricating layer on the substrate layer. In the coating liquid, the polymeric material and the block copolymer are dissolved in a solvent (the polymeric material and the block copolymer are uniformly mixed in the coating liquid). As a result, the block copolymer and the polymeric material become entangled in the surface lubricating layer.

[0109] Therefore, another embodiment of the present invention provides a medical appliance, which is a medical appliance having a substrate layer and a surface lubricating layer carried on at least a portion of the substrate layer, wherein the surface lubricating layer comprises: a block copolymer having a structural unit (A) from a reactive monomer having an epoxy group and a structural unit (B) from a hydrophilic monomer; and a polymer material selected from at least one of polyvinyl chloride and polyurethane, wherein the block copolymer and the polymer material are entangled with each other in the surface lubricating layer. In this embodiment, the terms such as block copolymer and polymer material are the same as those described in the above-mentioned <Manufacturing method of medical appliance>, and therefore description is omitted here. As described above, the content of the polymer material in the coating liquid is preferably less than the content of the block copolymer in the coating liquid. Therefore, the amount of the polymer material present in the surface lubricating layer is preferably less than the amount of the block copolymer present in the surface lubricating layer. At this time, the preferred existence ratio (content ratio) of the block copolymer and the polymer material present in the surface lubricating layer is the same as the preferred mixing ratio of the block copolymer and the polymer material in the coating liquid of the above-mentioned (polymer material).

[0110] Hereinafter, preferred embodiments of a medical device manufactured by the method according to the present invention will be described with reference to the accompanying drawings.

[0111] Figure 1 This is a partial cross-sectional view schematically showing the laminate structure of the surface of a representative embodiment of a medical device (also referred to simply as a "medical device" in this specification) manufactured by the method according to the present invention. Figure 2 This is a partial cross-sectional view schematically showing an example of a structure with a different surface layer structure as an application example of the present embodiment. Figure 1 and Figure 2 The reference numerals in the figures represent the following: 1 represents a substrate layer; 1a represents a core portion of the substrate layer; 1b represents a substrate surface layer; 2 represents a surface lubricating layer; and 10 represents a medical device manufactured by the method according to the present invention.

[0112] like Figure 1 、 Figure 2 As shown, the medical device 10 of this embodiment comprises a base layer 1 and a surface lubricating layer 2, wherein the surface lubricating layer 2 is provided on at least a portion of the base layer 1 (in the figure, an example of the base layer 1 being provided on the entire surface (whole surface) is shown) and comprises a block copolymer. Figure 1 、 Figure 2 In the embodiment, the surface lubricating layer 2 is formed on both sides of the substrate layer 1, but the present invention is not limited to the above-mentioned form, and can also be any of the following forms: a form formed on a single side of the substrate layer 1; a form formed on a part of a single side or both sides of the substrate layer 1, etc.

[0113] Hereinafter, the medical device will be described in detail for each component.

[0114] (Base material layer (base material))

[0115] The substrate layer used in this embodiment can be made of any material, and there are no particular limitations on the material. Specifically, the material constituting the substrate layer 1 includes metal materials, polymer materials, and ceramics. Specific examples of the material constituting the substrate layer 1 are those described in the coating step (II) above.

[0116] Here, the base material layer 1 may be composed entirely of any of the above materials. The base material layer 1 may be a multilayer structure formed by stacking multiple layers of different materials, or may be a structure formed by connecting components made of different materials to form different parts of the medical device. Alternatively, Figure 2As shown, the following structure may also be provided: on the surface of the substrate layer core 1a composed of any of the above materials, any of the other above materials is coated by an appropriate method to form the substrate surface layer 1b. As examples of the latter case, there can be cited: a structure in which a metal material is coated on the surface of the substrate layer core 1a formed of a resin material or the like by an appropriate method (electroplating, metal evaporation, sputtering, etc.) to form the substrate surface layer 1b; a structure in which a polymer material softer than the reinforcing material such as the metal material is coated on the surface of the substrate layer core 1a formed of a hard reinforcing material such as a metal material or ceramic material by an appropriate method (impregnation, spraying, coating / printing, etc.), or a structure in which the reinforcing material forming the substrate layer core 1a is composited with a polymer material to form the substrate surface layer 1b; and so on. In addition, the substrate layer core 1a may be a multilayer structure formed by stacking multiple layers of different materials, or may be a structure in which components of the medical device formed of different materials are connected together. In addition, another intermediate layer (not shown) may be further formed between the base material layer core 1a and the base material surface layer 1b. In addition, the base material surface layer 1b may be a multilayer structure formed by stacking multiple layers of different materials, or a structure formed by connecting components formed of different materials to form various parts of the medical device.

[0117] (Surface lubricating layer (coating layer))

[0118] The surface lubricating layer is carried on at least a portion of the substrate layer 1. The reason for carrying the surface lubricating layer 2 on at least a portion of the surface of the substrate layer 1 is that, in medical devices such as catheters, guidewires, and indwelling needles, it is not necessary for the entire surface (the entire surface) of these medical devices to be lubricated when wet. The surface lubricating layer can be carried only on the surface portion (sometimes a portion, sometimes the entire surface) where lubricity is required when wet. Therefore, as described above, the surface lubricating layer includes the following forms: Figure 1 、 Figure 2 The form shown is formed in a manner of covering both sides of the substrate layer as a whole; the form is formed in a manner of covering only one side of the substrate layer as a whole; the form is formed in a manner of covering part of both sides of the substrate layer in the same or different forms; the form is formed in a manner of covering part of one side of the substrate layer; and the like.

[0119] <Purpose of medical equipment>

[0120] Medical devices manufactured using the method of the present invention are used in contact with body fluids, blood, and the like. Their surfaces exhibit lubricity in aqueous liquids such as body fluids and physiological saline, improving operability and minimizing damage to tissues and mucous membranes. Specifically, these devices include catheters, guidewires, and indwelling needles for intravascular use. The following medical devices are also included.

[0121] (a) Tubes that are inserted orally or nasally into or placed in the digestive organs, such as gastric tubes, nutritional tubes, and intravenous feeding tubes.

[0122] (b) Oxygen catheters, oxygen cannulas, endotracheal tubes or cuffs, tracheotomy tubes or cuffs, endotracheal suction catheters, and other tubes that are inserted or placed in the respiratory tract or trachea through the mouth or nose.

[0123] (c) Catheters such as urethral catheters, urinary catheters, and urethral balloon catheters that are inserted into or left in the urethra or ureter.

[0124] (d) Catheters such as suction catheters, drainage catheters, and rectal catheters that are inserted into or left in various body cavities, organs, and tissues.

[0125] (e) Catheters inserted or placed in blood vessels, such as indwelling needles, IVH catheters, thermodilution catheters, angiographic catheters, vascular dilator catheters and dilators, or introducers, or guidewires and stylets used for these catheters.

[0126] (f) Artificial trachea, artificial bronchus, etc.

[0127] (g) Medical devices for extracorporeal circulation therapy (artificial lungs, artificial hearts, artificial kidneys, etc.), and their circuits

[0128] Example

[0129] The effects of the present invention are described using the following examples and comparative examples. However, the technical scope of the present invention is not limited to the following examples. It should be noted that, in the following examples, unless otherwise specified, the operation was carried out at room temperature (25°C). In addition, unless otherwise specified, "%" and "parts" refer to "mass %" and "mass parts", respectively.

[0130] Synthesis example 1

[0131] The following reaction was carried out to produce a block copolymer (1).

[0132] [Chemical Formula 1]

[0133]

[0134] After 29.7 g of triethylene glycol was added dropwise to 72.3 g of adipoyl chloride at 50°C, hydrochloric acid was removed under reduced pressure at 50°C for 3 hours to obtain an oligoester. Subsequently, 4.5 g of methyl ethyl ketone was added to 22.5 g of the obtained oligoester, and the resulting mixture was added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of dioctyl phosphate as a surfactant, and 120 g of water. The mixture was reacted at -5°C for 20 minutes. The obtained product was repeatedly washed with water and methanol, and then dried to obtain a polyperoxide (PPO) having multiple peroxide groups in the molecule.

[0135] Next, 0.5 g of this PPO, 9.5 g of glycidyl methacrylate (GMA), and 30 g of benzene as a solvent were polymerized while stirring at 80°C for 2 hours under reduced pressure. The resulting polymerization product was reprecipitated in diethyl ether to obtain polyglycidyl methacrylate (PPO-GMA) having multiple peroxide groups in the molecule.

[0136] Next, 1.0 g of the obtained PPO-GMA (equivalent to 7 mmol of GMA) was added to 9.0 g of N,N-dimethylacrylamide (DMAA) and 90 g of dimethyl sulfoxide as a solvent, and the mixture was reacted at 80°C for 18 hours. The product obtained after the reaction was reprecipitated in hexane and recovered to obtain a block copolymer (1) having epoxy groups in the molecule and exhibiting lubricity when wet (structural unit (A): structural unit (B) = GMA: DMAA = 1:14 (molar ratio)). The block copolymer (1) obtained in this manner was then subjected to a reaction with a molten-water mixture. 1 H-NMR and ATR-IR analyses confirmed the presence of epoxy groups in the molecule. The weight average molecular weight (Mw) of the block copolymer (1) measured by gel permeation chromatography (GPC, polystyrene equivalent) was approximately 1.5 million.

[0137] Example 1

[0138] Polyvinyl chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., Mw=50,000 or more) was dissolved in N,N-dimethylformamide (DMF) to a final concentration of 0.01% by mass in the coating solution (solution (1)). The block copolymer (1) synthesized in Synthesis Example 1 was added to and dissolved in the solution (1) to a final concentration of 4.5% by mass in the coating solution to prepare a coating solution (1).

[0139] A tube (outer diameter: 2.80 mm) made of nylon elastomer (VESTAMID E47-S1 manufactured by Evonik) was immersed in the above-mentioned coating liquid (1) and dried at room temperature (25°C) for 1 hour to remove DMF, thereby forming a coating film (1) on the surface of the tube (tube (1)). Furthermore, the tube (1) was stored in an oven at 110°C for 1 hour to heat-treat the coating film (1) (tube (1')). The tube (1') was dried at room temperature (25°C) to prepare a sample (coated tube) (1) having a coating layer (surface lubricating layer) (dry film thickness: 1 μm) on the surface, wherein the coating layer contained a cross-linked copolymer derived from the block copolymer (1).

[0140] Example 2

[0141] In Example 1, a sample (coated tube) (2) was prepared by the same method as in Example 1 except that polyurethane (polyester) (Elastollan (registered trademark) C95A manufactured by BASF Japan, Mw=10,000 or more) was used instead of polyvinyl chloride.

[0142] Example 3

[0143] In Example 1, a sample (coated tube) (3) was prepared by the same method as in Example 1 except that polyurethane (polyether-based) (Elastollan (registered trademark) 1195ATR manufactured by BASF Japan, Mw=10,000 or more) was used instead of polyvinyl chloride.

[0144] Example 4

[0145] In Example 1, a sample (coated tube) (4) was prepared by the same method as in Example 1 except that the final concentration of polyvinyl chloride in the coating liquid was changed to 0.001% by mass.

[0146] Example 5

[0147] In Example 1, a sample (coated tube) (5) was prepared by the same method as in Example 1 except that the final concentration of polyvinyl chloride in the coating liquid was changed to 0.005% by mass.

[0148] Example 6

[0149] In Example 1, a sample (coated tube) (6) was prepared by the same method as in Example 1 except that the final concentration of polyvinyl chloride in the coating liquid was changed to 0.1% by mass.

[0150] Example 7

[0151] In Example 1, a sample (coated tube) (7) was prepared by the same method as in Example 1 except that the final concentration of polyvinyl chloride in the coating liquid was changed to 0.5% by mass.

[0152] Example 8

[0153] In Example 1, a sample (coated tube) (8) was prepared by the same method as in Example 1 except that the final concentration of polyvinyl chloride in the coating liquid was changed to 2.0% by mass.

[0154] Example 9

[0155] In Example 1, a sample (coated tube) (9) was prepared by the same method as in Example 1 except that the final concentration of polyvinyl chloride in the coating liquid was changed to 3.0% by mass.

[0156] Example 10

[0157] In Example 1, a sample (coated tube) (10) was prepared by the same method as in Example 1 except that the final concentration of polyvinyl chloride in the coating liquid was changed to 4.0% by mass.

[0158] Example 11

[0159] In Example 1, a sample (coated tube) (11) was prepared by the same method as in Example 1 except that the final concentration of polyvinyl chloride in the coating liquid was changed to 4.5% by mass.

[0160] Example 12

[0161] Polyvinyl chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., Mw=50,000 or more) was dissolved in N,N-dimethylformamide (DMF) to a final concentration of 0.1% by mass in the coating solution (solution (2)). The block copolymer (1) synthesized in Synthesis Example 1 was added to and dissolved in the solution (2) to a final concentration of 4.5% by mass in the coating solution to prepare a coating solution (2).

[0162] A stainless steel rod (outer diameter: 1.50 mm) was immersed in the above-mentioned coating liquid (2) and dried at room temperature (25°C) for 1 hour to remove DMF and form a coating film (2) on the surface of the stainless steel rod (stainless steel rod (2)). Furthermore, the stainless steel rod (2) was stored in an oven at 110°C for 12 hours to heat-treat the coating film (2) (stainless steel rod (2')). The stainless steel rod (2') was dried at room temperature (25°C) to prepare a sample (coated stainless steel rod) (12) having a coating layer (surface lubricating layer)) (dry film thickness: 0.8 μm) on the surface, wherein the coating layer contained a cross-linked copolymer derived from the block copolymer (1).

[0163] Example 13

[0164] In Example 12, except that the final concentration of polyvinyl chloride in the coating liquid was changed to 0.5% by mass, a sample (coated stainless steel rod) (13) was prepared by the same method as in Example 12.

[0165] Comparative Example 1

[0166] The block copolymer (1) synthesized in Synthesis Example 1 was dissolved in N,N-dimethylformamide (DMF) so that the final concentration in the coating liquid became 4.5% by mass, thereby preparing a comparative coating liquid (1).

[0167] A tube (outer diameter: 2.80 mm) made of nylon elastomer (VESTAMID E47-S1 manufactured by Evonik) was immersed in the above-mentioned comparative coating liquid (1) and dried at room temperature (25°C) for 1 hour to remove DMF and form a coating film (3) on the tube surface (comparative tube (1)). Furthermore, the comparative tube (1) was stored in an oven at 110°C for 1 hour to heat-treat the coating film (3) (comparative tube (1')). The comparative tube (1') was dried at room temperature (25°C) to produce a comparative sample (comparative coated tube) (1) having a coating layer (surface lubricating layer) (dry film thickness: 1 μm) on the surface, wherein the coating layer contained a cross-linked copolymer derived from the block copolymer (1).

[0168] Comparative Example 2

[0169] Polystyrene was dissolved in N,N-dimethylformamide (DMF) to a final concentration of 0.1% by mass in the coating solution (comparative solution (2)). The block copolymer (1) synthesized in Synthesis Example 1 was added to the comparative solution (2) to a final concentration of 4.5% by mass in the coating solution and dissolved to prepare a comparative coating solution (2).

[0170] A tube (outer diameter: 2.80 mm) made of nylon elastomer (VESTAMID E47-S1 manufactured by Evonik) was immersed in the above-mentioned comparative coating liquid (2) and dried at room temperature (25°C) for 1 hour to remove DMF and form a coating film (4) on the tube surface (comparative tube (2)). Furthermore, the comparative tube (2) was stored in an oven at 110°C for 1 hour to heat-treat the coating film (4) (comparative tube (2')). The comparative tube (2') was dried at room temperature (25°C) to produce a comparative sample (comparative coated tube) (2) having a coating layer (surface lubricating layer) (dry film thickness: 1 μm) on the surface, wherein the coating layer contained a cross-linked copolymer derived from the block copolymer (1).

[0171] Comparative Example 3

[0172] The block copolymer (1) synthesized in Synthesis Example 1 was dissolved in N,N-dimethylformamide (DMF) so that the final concentration in the coating liquid became 4.5% by mass, thereby preparing a comparative coating liquid (3).

[0173] A stainless steel rod (outer diameter: 1.50 mm) was immersed in the above-mentioned comparative coating liquid (3) and dried at room temperature (25°C) for 1 hour to remove DMF and form a coating film (5) on the surface of the stainless steel rod (comparative stainless steel rod (3)). Furthermore, the comparative stainless steel rod (3) was stored in an oven at 110°C for 12 hours to heat-treat the coating film (5) (comparative stainless steel rod (3')). The comparative stainless steel rod (3') was dried at room temperature (25°C) to prepare a comparative sample (coated stainless steel rod) (3) having a coating layer (surface lubricating layer) on the surface (dry film thickness: 0.8 μm), wherein the coating layer contained a cross-linked copolymer derived from the block copolymer (1).

[0174] The sliding durability and sliding properties of the samples (1) to (13) prepared in Examples 1 to 13 and the comparative samples (1) to (3) prepared in Comparative Examples 1 to 3 were evaluated according to the following methods. The results are shown in Table 1 below. In Table 1 below, the block copolymer (1) synthesized in Synthesis Example 1 is represented as "p(GMA-b-DMAA)". In addition, the mixing ratio of the polymer material to 100 parts by mass of the block copolymer is represented as "polymer material / 100 parts of block copolymer".

[0175] [Evaluation of sliding durability]

[0176] The sliding durability (durability of the surface lubricating layer) of each sample was evaluated by the following method.

[0177] Each sample was immersed in tap water, held by hand, and rubbed along the major axis. This method was used to perform a sensory evaluation of sliding durability. The number of frictions until lubricity (smoothness) was impaired was measured to evaluate sliding durability. The greater the number of frictions, the better the sliding durability. It should be noted that the upper limit of friction was set to 50 times, and samples that maintained sliding properties at 50 friction times were recorded as >50.

[0178] [Evaluation of Sliding Properties]

[0179] The sliding properties (sliding properties of the surface lubricating layer) of each sample were evaluated by the following method.

[0180] Each sample was immersed in tap water, and the sample was held by hand and rubbed in the longitudinal direction. Using this method, the sliding properties were sensory evaluated according to the following evaluation criteria.

[0181] (Evaluation Criteria)

[0182] ◎: After 50 rubbing cycles, the coating state (coating state) did not change before and after rubbing, and the sliding properties were also excellent.

[0183] 0: The coating state does not change before and after friction, but the sliding property is slightly worse;

[0184] △: The coating state changes due to friction (such as roughness), but it maintains a certain degree of sliding properties even after 50 frictions; and

[0185] ×: The coating state changed due to friction, and after 50 cycles of friction, the coating peeled off partially or entirely in the evaluation area.

[0186] [Table 1]

[0187]

[0188] Table 1 above shows that a medical device having a surface lubricating layer having excellent sliding durability and sliding properties can be obtained by applying a coating liquid containing polyvinyl chloride or polyurethane on a base layer.

[0189] On the other hand, in the case of not using polyvinyl chloride or polyurethane in coating liquid, surface lubrication layer lacks sliding durability and slippage (comparative example 1, comparative example 3). It is speculated that its reason is, do not promote crosslinking or the polymerization of block copolymer, do not form a firm surface lubrication layer. In addition, in the case of using polystyrene in coating liquid, surface lubrication layer also lacks sliding durability and slippage (comparative example 2). It is speculated that its reason is, because polystyrene does not have electron-withdrawing property, therefore do not promote crosslinking or the polymerization of block copolymer, do not form a firm surface lubrication layer.

[0190] Comparison of Examples 1, 4 to 11 and the Comparative Examples shows that sufficient durability (sliding durability) can be achieved when the amount of polymer material added is 0.001% by mass or more. Furthermore, when the amount of polymer material added is 0.005% to 4.0% by mass, even better sliding properties are exhibited. This indicates that from the perspective of sliding properties, the amount of polymer material added is preferably 0.005% to 4.0% by mass.

[0191] Next, the sliding resistance of the samples (12) and (13) prepared in Examples 12 and 13 and the comparative sample (3) prepared in Comparative Example 3 was evaluated according to the following method. The results are shown in Table 2 below. In Table 2 below, the block copolymer (1) synthesized in Synthesis Example 1 is represented as "p(GMA-b-DMAA)". In addition, the mixing ratio of the polymer material to 100 parts by mass of the block copolymer is represented as "polymer material / 100 parts of block copolymer".

[0192] [Evaluation of sliding resistance]

[0193] Each sample was immersed in tap water and placed in a clamp tester (DL1000, manufactured by Oak River Technology) and slid 100 times under the conditions of a clamping force of 500 gf, a test speed of 8.3 mm / s, and a test stroke of 25 mm (clamping pad material: silicone, clamping pad height: 12.35 mm). Sliding properties were evaluated by measuring the test force after 100 slides. The lower the test force, the better the sliding durability and sliding properties.

[0194] [Table 2]

[0195]

[0196] Table 2 shows that a medical device having a surface lubricating layer having excellent sliding durability and sliding properties can be obtained by applying a coating liquid containing polyvinyl chloride on a base layer.

[0197] On the other hand, when polyvinyl chloride was not used in the coating solution, the surface lubricating layer lacked slip properties (Comparative Example 3). This is believed to be because crosslinking or polymerization of the block copolymer was not promoted, and a strong lubricating layer was not formed. Therefore, part of the surface lubricating layer peeled off after 100 slides.

[0198] Furthermore, when comparing Examples 12 and 13, the case where the amount of polyvinyl chloride added was 0.1% by mass (Example 12) exhibited superior sliding properties compared to the case where the amount was 0.5% by mass (Example 13). This is believed to be because increasing the amount of polyvinyl chloride added further promoted crosslinking or polymerization, resulting in a decrease in sliding properties.

[0199] This application is based on Japanese patent application No. 2023-037345 filed on March 10, 2023, the disclosure of which is incorporated herein by reference in its entirety.

[0200] Description of Reference Numerals

[0201] 10 Medical equipment,

[0202] 1 base material layer,

[0203] 1a base material layer core,

[0204] 1b substrate surface layer,

[0205] 2. Lubricating layer.

Claims

1. A method for manufacturing a medical device comprising a base layer and a surface lubricating layer carried on at least a portion of the base layer, the method comprising: preparing a coating liquid comprising a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, a polymer material of at least one selected from polyvinyl chloride and polyurethane, and a solvent; and The coating liquid is applied on the base material layer.

2. The method according to claim 1, wherein The content of the polymer material in the coating liquid is less than the content of the block copolymer in the coating liquid.

3. The method according to claim 1, wherein The coating liquid contains the polymer material in an amount of 0.001 mass % or more and less than 12 mass %.

4. The method according to claim 1, wherein The reactive monomer having an epoxy group includes at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether.

5. The method according to claim 1, wherein The hydrophilic monomer includes at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinyl pyrrolidone.

6. A medical device comprising a base layer and a surface lubricating layer carried on at least a portion of the base layer. The surface lubricating layer comprises: a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer; and a polymer material selected from at least one of polyvinyl chloride and polyurethane, In the surface lubricating layer, the block copolymer and the polymer material are entangled with each other.

7. The medical device according to claim 6, wherein The amount of the polymer material present in the surface lubricating layer is less than the amount of the block copolymer present in the surface lubricating layer.

8. The medical device according to claim 6, wherein The reactive monomer having an epoxy group includes at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether.

9. The medical device according to claim 6, wherein The hydrophilic monomer includes at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinyl pyrrolidone.

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