Medical instrument and manufacturing method therefor

Abstract

Provided is a medical instrument that has a lubricating layer comprising a lubricating layer structure with improved durability (especially sliding durability) while maintaining good lubricity. Also provided is a manufacturing method therefor.　A medical instrument according to the present invention comprises a substrate layer and a lubricating layer that is supported on at least a portion of the substrate layer and swells when in contact with an aqueous solvent, wherein: the lubricating layer contains a polymer having a constituent unit A derived from a hydrophilic monomer; in an observation image when the lubricating layer has swelled, the surface of the lubricating layer has a net structure and a plurality of holes each surrounded by the net structure; and the net structure and the holes satisfy condition (1) or condition (2). (1) The holes have an average area of at least 1 μm2 and a maximum area of at most 30 μm2 in a planar view. (2) The holes have an average area of at least 1 μm2 and a maximum area of more than 30 μm2 in a planar view, and the average value of the net thickness of the net structure is at least 1 μm.

Description

Medical device and its manufacturing method

[0001] The present invention relates to a medical device and a method for manufacturing the same.

[0002] Medical devices inserted into living bodies, such as catheters and guidewires, are required to exhibit excellent lubricity in order to reduce tissue damage to blood vessels and improve operability for the surgeon. For this reason, methods for coating the surface of a medical device's base layer with a hydrophilic polymer having lubricity have been developed and put into practical use. Meanwhile, in order to maintain the operability of such medical devices, it is also important that the hydrophilic polymer having lubricity can be maintained on the surface of the base layer during use by the surgeon. Therefore, coatings with hydrophilic polymers are required to have not only excellent lubricity but also durability against loads such as abrasion and abrasion.

[0003] From this perspective, Japanese Patent Laid-Open Publication No. 8-33704 (corresponding to the specification of U.S. Pat. No. 5,670,558) 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 this polymer solution to cause it to swell, and the polymer is crosslinked or polymerized on the surface of the substrate layer, thereby forming a surface lubricating layer on the surface of the substrate layer.

[0004] According to the technology disclosed in the above document, a surface lubricating layer exhibiting good lubricity can be fixed to a substrate.

[0005] The above-mentioned document discloses that it is preferable to use a block copolymer consisting of a hydrophilic portion that exhibits lubricity and a portion having an epoxy group as the water-soluble or water-swellable polymer. When such a block copolymer is used, the block copolymer can be crosslinked or polymerized by heating, thereby forming a surface lubricating layer that is relatively difficult to peel off.

[0006] On the other hand, as medical procedures become more complex, the operation of medical devices may take even longer. Therefore, in order to maintain good operability of medical devices for a longer period of time, even when treating a lesion through a very complex biological lumen, a technology is required that further improves the lubricity (durability) of the surface of the medical device compared to conventional technologies. More specifically, there is a demand for medical devices that can maintain high lubricity and have excellent sliding durability even when the medical device repeatedly slides under harsh conditions (e.g., when the medical device repeatedly slides to deliver a medical device to a lesion through a portion of a biological lumen with a small bending radius, a portion of a biological lumen with a continuous bending portion, a portion of a biological lumen with a narrow inner diameter, etc.).

[0007] Therefore, there is a demand for technology that can improve the durability (especially sliding durability) of the lubricating layer of medical devices and support increasingly complex and sophisticated medical procedures.

[0008] The present invention has been made in consideration of the above circumstances, and aims to provide a medical device having a lubricating layer with a lubricating layer structure that maintains good lubricity while improving durability (particularly sliding durability), and a method for manufacturing the same.

[0009] The present inventors have conducted extensive research to solve the above problems, and as a result have found that the above problems can be solved by forming a lubricating layer having a specific lubricating layer structure, which has led to the completion of the present invention.

[0010] The above problems can be solved by the present invention having the following configuration, and the present invention includes the following aspects and configurations.

[0011] One aspect of the present invention is a medical device comprising: 1. a base layer; and a lubricating layer carried on at least a portion of the base layer and which swells when in contact with an aqueous solvent, wherein the lubricating layer contains a polymer having a structural unit A derived from a hydrophilic monomer, and the surface of the lubricating layer has a network structure and a plurality of pores surrounded by the network structure in an observation image of the lubricating layer when swollen, and the network structure and the pores satisfy the following condition (1) or the following condition (2): (1) the pores have an average area of ​​1 μm in a plan view. ２or more, and the maximum area is 30 μm ２ (2) The pores have an average area of ​​1 μm or less in plan view. ２ or more, and the maximum area is 30 μm ２ and the average mesh thickness of the mesh structure is 1 μm or more.

[0012] 2. In the medical device described in 1 above, the pores have an average area of ​​1 to 10 μm in plan view. ２ and the ratio of the maximum area of ​​the hole to the average mesh thickness of the mesh structure (the maximum area of ​​the hole (unit: μm ２ 3. In the medical device according to the above 1. or 2., the pores preferably have an average area of ​​3 to 10 μm in plan view. ２ 4. In the medical device according to any one of the above items 1 to 3, the pores preferably have an average area of ​​3 to 10 μm in plan view. ２ and the maximum area is 30 μm ２ Over 100 μm ２ or less, and the ratio of the maximum area of ​​the hole to the average mesh thickness of the mesh structure (the maximum area of ​​the hole (unit: μm ２) / average mesh thickness (unit: μm) of the network structure is preferably 20 to 50; 5. In the medical device described in any of 1. to 4. above, the surface of the lubricating layer preferably has less than 5 needle-like crystals with a length of 1 μm or more in an image observed at 5000 times when the lubricating layer is swollen; 6. The medical device described in 1. to 5. above, 6. In the medical device described in any one of 1. to 5. above, the structural unit A derived from the hydrophilic monomer is preferably a structural unit derived from at least one monomer selected from the group consisting of acrylic acid, acrylamide, N-methylacrylamide, N,N-dimethylacrylamide, N-ethylacrylamide, N,N-diethylacrylamide, N,N-dimethylaminopropylacrylamide, N,N-dimethylaminopropylmethacrylamide, 2-acrylamido-2-methylpropanesulfonic acid, N-(2-hydroxyethyl)acrylamide, N-(2-hydroxypropyl)acrylamide, N-(2-hydroxybutyl)acrylamide, N-vinyl-2-pyrrolidone, polyethylene glycol monoacrylate, polyethylene glycol monomethacrylate, alkoxypolyethylene glycol monoacrylate, and alkoxypolyethylene glycol monomethacrylate; 7. In the medical device described in any one of 1. to 5. above, the lubricating layer preferably comprises a copolymer having the structural unit A derived from the hydrophilic monomer and the structural unit B derived from a hydrophobic monomer having an epoxy group; 8. In the medical device described in 7. above, the lubricating layer preferably comprises a copolymer having the structural unit A derived from the hydrophilic monomer and the structural unit B derived from a hydrophobic monomer having an epoxy group; 8. In the medical device described in 7. or 8. above, it is preferable that the structural unit B derived from the hydrophobic monomer having an epoxy group is a structural unit derived from at least one monomer selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl acrylate, and β-methylglycidyl methacrylate; 9. In the medical device described in 7. or 8. above, it is preferable that the copolymer contains the structural unit A derived from the hydrophilic monomer in a ratio of 5 to 50 moles per mole of the structural unit B derived from the hydrophobic monomer having an epoxy group;10. In the medical device according to any one of 1. to 9. above, the sliding resistance value of the lubricating layer as determined by sliding resistance value evaluation is preferably less than 20 gf; 11. In the medical device according to any one of 1. to 10. above, the lubricating layer is preferably free of photopolymerization initiators and their residues; 12. In the medical device according to any one of 1. to 11. above, the lubricating layer is preferably formed by curing with an electron beam; 13. In the medical device according to any one of 1. to 12. above, the medical device is preferably a catheter, a stent, or a guidewire;

[0013] Another aspect of the present invention is a method for producing a medical device, comprising: applying a coating liquid containing a polymer having a structural unit A derived from a hydrophilic monomer and a solvent to at least a portion of a substrate layer to form a precursor layer on at least a portion of the substrate layer; and irradiating the precursor layer with an electron beam at an irradiation dose of more than 0 kGy and less than 500 kGy to form a lubricating layer on the substrate layer that swells when contacted with an aqueous solvent, wherein the surface of the lubricating layer has a network structure and a plurality of pores surrounded by the network structure in an observation image of the lubricating layer when swollen, and the network structure and the pores satisfy the following condition (1) or the following condition (2): (1) the pores have an average area of ​​1 μm in a plan view. ２ or more, and the maximum area is 30 μm ２ (2) The pores have an average area of ​​1 μm or less in plan view. ２ or more, and the maximum area is 30 μm ２ and the average mesh thickness of the mesh structure is 1 μm or more.

[0014] 15. In the method for producing a medical device as described in 14 above, it is preferable that the precursor layer is irradiated with electron beams at a dose of more than 5 kGy and less than 200 kGy.

[0015] FIG. 1 is an SEM image of a surface observation sample of Comparative Example 1. FIG. 2 is an SEM image of a surface observation sample of Comparative Example 2. FIG. 3 is an SEM image of a surface observation sample of Example 1. FIG. 4 is an SEM image of a surface observation sample of Example 2. FIG. 5 is an SEM image of a surface observation sample of Example 3. FIG. 6 is an SEM image of a surface observation sample of Comparative Example 3. FIG. 7 is an SEM image of a surface observation sample of Comparative Example 4. FIG. 8 is an SEM image of a surface observation sample of Example 4. FIG. 9 is an SEM image of a surface observation sample of Example 5. FIG. 10 is an image (binarized image) obtained by binarizing the SEM image of the surface observation sample of Example 2. FIG. 11 is an image (edge-processed image) obtained by edge-processing the binarized image of FIG. 10.

[0016] One aspect of the present invention relates to a medical device comprising a base layer and a lubricating layer carried on at least a portion of the base layer and which swells when in contact with an aqueous solvent, wherein the lubricating layer contains a polymer having a structural unit A derived from a hydrophilic monomer, and the surface of the lubricating layer has a network structure and a plurality of pores surrounded by the network structure in an observation image of the lubricating layer when swollen, and the network structure and the pores satisfy the following condition (1) or the following condition (2): (1) The pores have an average area of ​​1 μm in plan view. ２ or more, and the maximum area is 30 μm ２ (2) The pores have an average area of ​​1 μm or less in plan view. ２ or more, and the maximum area is 30 μm ２ and the average mesh thickness of the mesh structure is 1 μm or more.

[0017] Another aspect of the present invention relates to a method for producing a medical device, comprising: applying a coating liquid containing a polymer having a structural unit A derived from a hydrophilic monomer and a solvent to at least a portion of a substrate layer to form a precursor layer on at least a portion of the substrate layer; and irradiating the precursor layer with an electron beam at an irradiation dose of more than 0 kGy and less than 500 kGy to form a lubricating layer on the substrate layer that swells when contacted with an aqueous solvent, wherein the surface of the lubricating layer has a network structure and a plurality of pores surrounded by the network structure in an observation image of the lubricating layer when swollen, and the network structure and the pores satisfy the following condition (1) or the following condition (2): (1) the pores have an average area of ​​1 μm in a plan view. ２ or more, and the maximum area is 30 μm ２ (2) The pores have an average area of ​​1 μm or less in plan view. ２ or more, and the maximum area is 30 μm ２ and the average mesh thickness of the mesh structure is 1 μm or more.

[0018] With this configuration, it is possible to provide a medical device having a lubricating layer with a lubricating layer structure that maintains good lubricity while improving durability (particularly sliding durability).

[0019] As used herein, the term "X to Y" indicating a range includes X and Y and means "X or greater and Y or less." Furthermore, "X and / or Y" refers to at least one of X and Y, and encompasses X alone, Y alone, and a combination of X and Y. As used herein, the term "(meth)acrylic" encompasses both acrylic and methacrylic. Thus, for example, the term "(meth)acrylic acid" encompasses both acrylic acid and methacrylic acid. Similarly, the term "(meth)acryloyl" encompasses both acryloyl and methacryloyl. Thus, for example, the term "(meth)acryloyl group" encompasses both acryloyl and methacryloyl groups. Similarly, the term "(meth)acrylate" encompasses both acrylate and methacrylate. For example, the term "alkoxyalkyl (meth)acrylate" encompasses both alkoxyalkyl acrylate and alkoxyalkyl methacrylate.

[0020] In this specification, when a certain structural unit is defined as being "derived from" a certain monomer, it means that the structural unit is a structural unit that is generated by a condensation reaction of a reactive group in the corresponding monomer, that is generated by cleavage of an epoxy group in the corresponding monomer, and / or that is generated by cleavage of an ethylenically unsaturated group (polymerizable unsaturated double bond) in the corresponding monomer.

[0021] Unless otherwise specified, the operations and measurements of physical properties are carried out at room temperature (20 to 25°C) and a relative humidity of 40 to 60% RH.

[0022] <Medical Device> A medical device according to one aspect of the present invention comprises a substrate layer and a lubricating layer supported on at least a portion of the substrate layer and swells when in contact with an aqueous solvent. The lubricating layer provided on the medical device according to the present invention comprises a polymer having a structural unit A derived from a hydrophilic monomer, and the surface of the lubricating layer has a network structure and a plurality of pores surrounded by the network structure in an observation image of the lubricating layer when swollen, and the network structure and the pores satisfy the following condition (1) or the following condition (2): (1) the pores have an average area of ​​1 μm in plan view, ２ or more, and the maximum area is 30 μm ２ (2) The pores have an average area of ​​1 μm or less in plan view. ２ or more, and the maximum area is 30 μm ２ and the average mesh thickness of the mesh structure is 1 μm or more. A medical device having the above configuration is hereinafter also referred to as "the medical device according to the present invention" or "the medical device".

[0023] In this specification, the lubricating layer that swells upon contact with an aqueous solvent is also simply referred to as the "lubricating layer according to the present invention" or "lubricating layer." The network structure observed in an observation image of the lubricating layer when swollen is also simply referred to as the "network structure according to the present invention" or "network structure." In this specification, the multiple pores surrounded by the network structure observed in an observation image of the lubricating layer when swollen are also simply referred to as the "pores according to the present invention" or "pores." In this specification, the above condition (1) is also referred to as "condition (1) according to the present invention" or "condition (1)." In this specification, the above condition (2) is also referred to as "condition (2) according to the present invention" or "condition (2)."

[0024] In the medical device according to the present invention, the surface of the lubricating layer has a network structure that is observed in an observation image of the lubricating layer when swollen, and a plurality of pores surrounded by the network structure, and the network structure and pores satisfy specific condition (1) or condition (2). Because the lubricating layer has such a specific lubricating layer structure, the medical device according to the present invention not only has good lubricity when wet (for example, when in contact with body fluids such as blood or aqueous liquids such as physiological saline; the same applies hereinafter), but also has excellent durability (particularly sliding durability).

[0025] The mechanism by which the medical device according to the present invention exhibits the above-mentioned effects is not completely clear, and although the invention is not bound by any theory, the following mechanism is presumed: The pores formed on the surface of the lubricating layer according to the present invention have an average area of ​​1 μm when swollen. ２ or more (conditions (1) and (2)). In this way, the lubricating layer has an average area of ​​1 μm ２ By having pores with an average area of ​​1 μm or more, a sufficient amount of water (water molecules) can be taken into the pores when wet, and therefore excellent lubricity (slipperiness) can be exhibited. ２ If the thickness is less than this, a sufficient amount of water (water molecules) cannot be taken into the pores, the swelling property of the lubricating layer decreases, and excellent lubricity (slidability) cannot be obtained.

[0026] In addition, as defined in the condition (1), the maximum area of ​​the holes formed in the lubricating layer is 30 μm２ If the maximum area of ​​the pores is 30 μm or less, the network structure is formed densely (at high density), the strength of the lubricating layer structure as a whole is increased, and the durability (especially the sliding durability) of the lubricating layer is improved. ２ If the average thickness of the mesh structure (mesh thickness) is 1 μm or more, the strength of the mesh structure itself increases, resulting in improved durability (especially sliding durability) of the lubricating layer. ２ If the average value of the thickness (mesh thickness) of the network structure is less than 1 μm, good lubricity (sliding property) can be obtained due to the size of the holes, but the strength of the network structure itself is reduced because the network thickness is too thin, and the durability (particularly, sliding durability) of the lubricating layer is reduced. Specifically, if the average value of the thickness (mesh thickness) of the network structure is less than 1 μm, the polymer forming the lubricating layer is likely to be detached during sliding, and the durability (particularly, sliding durability) of the lubricating layer is presumed to be reduced.

[0027] As described above, by providing a lubricating layer structure having a network structure and pores that satisfy condition (1) or condition (2), the medical device according to the present invention can maintain excellent lubricity and exhibit excellent lubrication maintenance (sliding durability) even when the medical device is repeatedly slid under severe conditions (for example, when the medical device is repeatedly slid to deliver a medical instrument to a lesion site through a portion of a biological lumen with a small bending radius, a portion of a biological lumen with continuous bends, a portion of a biological lumen with a narrow inner diameter, etc.). Therefore, according to the present invention, it is possible to provide a medical device having a lubricating layer with a lubricating layer structure that maintains good lubricity and has improved durability (particularly sliding durability), and a method for producing the same.

[0028] Preferred embodiments of the present invention will be described below. Note that the present invention is not limited to the following embodiments, and various modifications can be made within the scope of the claims. Furthermore, the embodiments described in this specification can be arbitrarily combined to form other embodiments.

[0029] Throughout this specification, unless otherwise specified, singular expressions should be understood to include the plural concept. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept, unless otherwise specified. Furthermore, terms used in this specification should be understood to be used in the sense commonly used in the art, unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification (including definitions) will prevail.

[0030] [Substrate Layer (Substrate)] The substrate layer (substrate) used in the present invention may be made of any material and can be appropriately selected depending on the application. Specifically, materials constituting (forming) the substrate layer include metal materials, polymer materials, ceramics, etc. Here, the substrate layer may be entirely made of any of the above materials, or may have a structure in which the surface of a substrate layer core made of any of the above materials is coated with any of the other materials by an appropriate method to form a substrate surface layer. Examples of the latter include a substrate surface layer formed by coating the surface of a substrate core made of a resin material or the like with a metal material by an appropriate method (conventionally known methods such as plating, metal vapor deposition, sputtering, etc.); a substrate surface layer formed by coating the surface of a substrate core made of a hard reinforcing material such as a metal or ceramic material with a polymer material that is softer than the reinforcing material, such as a metal material, by an appropriate method (conventionally known methods such as dipping, spraying, coating, printing, etc.); or a substrate surface layer formed by combining the reinforcing material of the substrate core and the polymer material of the substrate surface layer (by an appropriate reaction treatment). Thus, the substrate core may be a multilayer structure formed by laminating different materials in multiple layers, or a structure (composite) in which components formed of different materials are joined for each portion of the medical device. Furthermore, a separate middle layer may be formed between the substrate core and the substrate surface layer. Furthermore, the substrate surface layer may also be a multilayer structure formed by laminating different materials in multiple layers, or a structure (composite) in which components formed of different materials are joined for each portion of the medical device.

[0031] Among the materials constituting (forming) the base layer, the metal material is not particularly limited, and metal materials commonly used for medical devices such as catheters, stents, and guidewires can be used. Specific examples include various stainless steels (SUS) such as SUS304, SUS316, SUS316L, SUS420J2, and SUS630, as well as gold, platinum, silver, copper, nickel, cobalt, titanium, iron, aluminum, tin, and various alloys such as nickel-titanium (Ni-Ti) alloys, nickel-cobalt (Ni-Co) alloys, cobalt-chromium (Co-Cr) alloys, and zinc-tungsten (Zn-W) alloys. These may be used alone or in combination of two or more. The metal material may be appropriately selected from those optimal for the base layer of the intended use, such as a catheter, stent, or guidewire.

[0032] Furthermore, among the materials constituting (forming) the base layer, the polymeric material (resin material or elastomer material) is not particularly limited, and polymeric materials commonly used in medical devices such as catheters, stents, and guidewires can be used. Specific examples of the resin include polyamide resin, polyethylene resins such as linear low-density polyethylene (LLDPE), low-density polyethylene (LDPE), high-density polyethylene (HDPE), and modified polyethylene, polyolefin resins such as polypropylene resin, modified polyolefin resin, cyclic polyolefin resin, epoxy resin, polyurethane resin, diallyl phthalate resin (allyl resin), polycarbonate resin, fluororesins such as polytetrafluoroethylene (PTFE) and ethylene tetrafluoroethylene (ETFE; Ethylene Tetra Fluoro Ethylene), amino resins (urea resin, melamine resin, benzoguanamine resin), polyester resins such as polyethylene terephthalate resin and polybutylene terephthalate resin, styrene resins such as polystyrene, acrylic resin, polyacetal resin, vinyl acetate resin, phenolic resin, vinyl chloride resin (polyvinyl chloride (PVC)), silicone resin, polyether resins such as polyether ether ketone (PEEK), and polyimide resin. Thermoplastic elastomers such as polyurethane elastomers, polyester elastomers, and polyamide elastomers (nylon elastomers) can also be used as materials for the base layer. These may be used alone or in combination of two or more. The polymer material may be appropriately selected from those that are optimal for the base layer of the intended use, such as a catheter, stent, or guidewire.

[0033] The shape of the substrate layer is not particularly limited, and may be a sheet, a wire, a tube, or the like, and may be selected appropriately depending on the mode of use.

[0034] [Lubricating layer] The lubricating layer is formed (carried) on at least a part of the substrate layer (substrate).Here, the reason why the lubricating layer is formed (carried) on at least a part of the surface of the substrate layer is that in medical devices such as catheters, stents, and guidewires, which are used for this purpose, it is not necessary for all surfaces (the entire surface) of these medical devices to have lubricity when wet, and the lubricating layer only needs to be carried on the surface part (sometimes a part or sometimes all) that is required to have lubricity when wet.Therefore, for example, when the substrate layer is tubular (tube-shaped), the lubricating layer includes the form of being formed so as to cover the entire outer surface of the substrate layer; the form of being formed so as to cover the entire inner surface of the substrate layer; the form of being formed so as to cover the outer surface and part of the inner surface of the substrate layer in the same or different forms; the form of being formed so as to cover part of the outer surface or inner surface of the substrate layer.In addition, when the substrate layer is linear (wire-shaped), the lubricating layer includes the form of being formed so as to cover the entire outer surface of the substrate layer; the form of being formed so as to cover part of the outer surface of the substrate layer. Furthermore, when the substrate layer is in the form of a sheet, the lubricating layer may be formed so as to cover the entirety of one side of the substrate layer; so as to cover the entirety of both sides of the substrate layer; so as to cover parts of both sides of the substrate layer in the same or different forms; or so as to cover parts of one side of the substrate layer.

[0035] The lubricating layer according to the present invention contains a polymer having a structural unit A derived from a hydrophilic monomer, as described below, and swells upon contact with an aqueous solvent. The aqueous solvent is not particularly limited, and examples thereof include water (RO water, pure water, ion-exchanged water, distilled water, etc.), saline, and phosphate-buffered saline (PBS). In this specification, the term "observation image of the lubricating layer when swollen" refers to an observation image of the lubricating layer in a swollen state upon contact with water. The term "swollen state" refers to a state in which the lubricating layer absorbs the aqueous solvent, resulting in an increase in volume and swelling. Specifically, upon contact with an aqueous solvent, aqueous solvent (e.g., water molecules) is absorbed between the molecular chains of the polymer constituting the lubricating layer, softening the lubricating layer and increasing its volume. To form a lubricating layer that swells upon contact with an aqueous solvent, the lubricating layer need only contain a polymer having a structural unit A derived from a hydrophilic monomer, as described below.

[0036] The surface of the lubricating layer according to the present invention has a network structure and a plurality of pores surrounded by the network structure. Here, the network structure and pores are observed in an observation image of the lubricating layer when swollen. In the lubricating layer, the network structure has a structure (three-dimensional network structure) in which the polymers constituting the lubricating layer are connected three-dimensionally. Furthermore, the pores are spatial regions surrounded by the network structure and are generated due to the formation of the network structure. In other words, the network structure in the lubricating layer can function as a skeleton for forming the pores.

[0037] One of the features of the medical device according to the present invention is that the network structure and pores observed when the swollen lubricating layer surface is observed in plan view have a specific structure. In this case, the network structure and pore structure (area, mesh thickness) are analyzed based on an observation image of the lubricating layer when swollen, and specifically, are determined by analyzing an SEM image obtained by the method described in the section "SEM observation of lubricating layer (when swollen)" of the Examples using the method described in the section "Analysis of network structure."

[0038] In the lubricating layer according to the present invention, the network structure and the pores satisfy the following condition (1) or the following condition (2): (1) The pores have an average area of ​​1 μm in plan view. ２or more, and the maximum area is 30 μm ２ (2) The hole has an average area of ​​1 μm or less in plan view. ２ or more, and the maximum area is 30 μm ２ and the average mesh thickness of the mesh structure is 1 μm or more; the above condition (1) is a configuration in which the pores are relatively small and the mesh structure is formed densely (at high density), and the above condition (2) is a configuration in which the pores are relatively large and the mesh structure itself (mesh thickness) is thick. By satisfying either the above condition (1) or condition (2), the medical device according to the present invention can maintain excellent lubricity and exhibit excellent lubrication maintenance (sliding durability).

[0039] Condition (1) and Condition (2): Average Area of ​​Holes In both Condition (1) and Condition (2), the average area of ​​the holes in a plan view is 1 μm ２ The average area of ​​the pores is 2 μm ２ It is preferable that it is 3 μm or more. ２ More preferably, it is 5 μm or more. ２ The larger the average area of ​​the pores, the easier it is for water (water molecules) to be taken into the pores when wet, and the lubricity (slipperiness) is further improved. On the other hand, there is no particular upper limit to the average area of ​​the pores, but it is preferably 30 μm or more, for example. ２ less than 20 μm ２ It may be less than 10 μm ２ It may be less than 7 μm ２ Therefore, the average area of ​​the pores may be, for example, 1 to 30 μm ２ and 1 to 20 μm ２ may be 1 to 10 μm ２ Furthermore, the average area of ​​the pores may be 2 to 10 μm ２ It is preferable that the thickness is 3 to 10 μm. ２ More preferably, it is 5 to 10 μm ２ It is even more preferable that the thickness is 5 to 7 μm. ２ It is particularly preferable that

[0040] Condition (1): Maximum Area of ​​Holes In condition (1), the maximum area of ​​the holes in a plan view is 30 μm２ The maximum area of ​​the hole is 25 μm ２ It is preferably 20 μm or less. ２ The smaller the maximum area of ​​the pores, the denser (higher density) the network structure is formed, the stronger the overall lubricating layer structure becomes, and the durability (particularly sliding durability) of the lubricating layer is further improved. On the other hand, there is no particular lower limit for the maximum area of ​​the pores, but it is preferably 1 μm or less, for example. ２ More than 5 μm ２ It may be 10 μm or more. ２ Therefore, in the condition (1), the maximum area of ​​the hole is, for example, 1 μm ２ More than 30 μm ２ or less, 5 to 25 μm ２ It is preferable that the thickness is 10 to 20 μm. ２ It is more preferable that:

[0041] Condition (1): Average mesh thickness of the mesh structure When condition (1) is satisfied, the average mesh thickness of the mesh structure is not particularly limited. The average mesh thickness of the mesh structure mainly contributes to the durability of the lubricating layer (particularly, sliding durability), and a lubricating layer with sufficient durability is formed when the maximum area of ​​the pores satisfies the condition (1). In condition (1), the average mesh thickness of the mesh structure may be, for example, 0.01 to 12.8 μm (less than half the length of the long side of the observed image), 0.3 to 5 μm, or 0.5 to 3 μm.

[0042] Condition (2): Maximum Area of ​​Holes In condition (2), the maximum area of ​​the holes in a plan view is 30 μm ２ The maximum area of ​​the hole is 40 μm ２ It is preferable that it is 50 μm or more. ２ The larger the maximum area of ​​the pores, the easier it is for water (water molecules) to be taken into the pores when wet, and the lubricity (slipperiness) is further improved. On the other hand, there is no particular upper limit to the maximum area of ​​the pores, but it is preferably 250 μm or more, for example. ２ less than half the area of ​​the entire observed image, and ２ It may be less than 80 μm ２Therefore, in the condition (2), the maximum area of ​​the hole may be, for example, 30 μm ２ Over 250 μm ２ less than or equal to 30 μm ２ Over 100 μm ２ It may be 40 to 100 μm or less, ２ It is preferable that the thickness is 50 to 80 μm. ２ It is more preferable that:

[0043] Condition (2): Average mesh thickness of the mesh structure In condition (2), the average mesh thickness of the mesh structure is 1 μm or more. The average mesh thickness of the mesh structure is preferably 1.1 μm or more, more preferably 1.3 μm or more, and particularly preferably 1.4 μm or more. The larger the average thickness (mesh thickness) of the mesh structure, the stronger the mesh structure itself is, and the more improved the durability (particularly, sliding durability) of the lubricating layer is. On the other hand, the upper limit of the average mesh thickness of the mesh structure is not particularly limited, but is, for example, 12.8 μm or less (less than half the length of the long side of the observed image), and may be 5 μm or less, or may be 3 μm or less. Therefore, in condition (2), the average mesh thickness of the mesh structure is, for example, 1 to 12.8 μm, preferably 1.1 to 5 μm, more preferably 1.3 to 5 μm, and particularly preferably 1.4 to 3 μm.

[0044] <<Maximum Area of ​​Holes / Average Mesh Thickness of Mesh Structure>> The lubricating layer (mesh structure and holes) according to the present invention satisfies either of the above conditions (1) and (2), and also satisfies the ratio of the maximum area of ​​the holes to the average mesh thickness of the mesh structure (maximum area of ​​holes (unit: μm ２ It is preferable that the ratio of the maximum area of ​​the holes to the average mesh thickness of the mesh structure (unit: μm) is within the following range. ２) / average mesh thickness of the mesh structure (unit: μm)) is also simply referred to as "average maximum area / average mesh thickness." That is, the lubricating layer (mesh structure and pores) according to the present invention not only satisfies either of the above conditions (1) or (2), but also preferably has an average maximum area / mesh thickness of 20 to 50, more preferably 25 to 40, and particularly preferably 25.5 to 40. When the ratio is within the above range, the network structure is formed with a moderate density, and when the lubricating layer is wet, it is easy to capture a moderate amount of water (water molecules) into the pores, thereby improving the durability and lubricity (slipperiness) of the lubricating layer in a balanced manner. Note that, although the average maximum area / mesh thickness is preferably within the above range, it is also sufficiently usable if it is outside the above range as long as it does not affect the effects of the present invention. For example, from the perspective of forming a lubricating layer with good lubricity (slipperiness), the average maximum area / mesh thickness may be greater than 1 or may be less than 1. Regardless of the range of the average value of maximum area / mesh thickness, the lubricating layer according to the present invention has a hole area of ​​1 μm ２ By satisfying the above, sufficient lubricity can be exhibited, but from the viewpoint of obtaining better lubricity (slipperiness), it is preferable that the average value of maximum area / mesh thickness exceeds 1.

[0045] <<Preferred Embodiment>> The lubricating layer (network structure and pores) according to the present invention preferably satisfies the above-mentioned condition (1) or (2), and further satisfies a combination of the preferred ranges for the average area and maximum area of ​​the pores, the average mesh thickness of the mesh structure, and the average maximum area / average mesh thickness described above. For example, the lubricating layer (network structure and pores) according to the present invention preferably satisfies the above-mentioned condition (1) or (2), and further satisfies at least one of the following embodiments: (i) The pores have an average area of ​​1 to 10 μm in plan view. ２ and the average value of maximum area / mesh thickness is 20 to 50; (ii) the hole portion has an average area of ​​3 to 10 μm in plan view. ２ (iii) The pores have an average area of ​​3 to 10 μm in plan view. ２ and the maximum area is 30 μm ２ Over 100 μm２ (iv) The average area of ​​the holes in plan view is 1 to 10 μm or less, and the average value of the maximum area / mesh thickness is 20 to 50; ２ and the maximum area is 5 to 25 μm ２ and the average mesh thickness of the mesh structure is 0.3 to 5 μm; (v) the hole portion has an average area of ​​1 to 10 μm in plan view. ２ and the maximum area is 5 to 25 μm ２ (vi) the average value of the maximum area / mesh thickness is 25 to 40; (vii) the hole portion has an average area of ​​5 to 7 μm in plan view. ２ (viii) The average value of maximum area / mesh thickness is 25.5 to 40.

[0046] In another embodiment, the lubricating layer (network structure and pores) of the present invention preferably satisfies the above condition (2). Furthermore, the lubricating layer (network structure and pores) of the present invention preferably satisfies the above condition (2) and also satisfies at least one of the above features (i) to (iii) and (vi) to (viii). More preferably, the lubricating layer (network structure and pores) of the present invention satisfies the above condition (2) and also satisfies at least one of the above features (ii), (iii), (vii), and (viii).

[0047] The medical device according to the present invention has a lubricating layer having the specific lubricating layer structure described above. The area of ​​each pore in such a lubricating layer structure and the mesh thickness of the mesh structure can be controlled by the composition of the polymer constituting the lubricating layer, curing conditions, etc., as described in detail below.

[0048] <Polymer Having a Hydrophilic Monomer-Derived Structural Unit A> The lubricating layer contains a polymer having a hydrophilic monomer-derived structural unit A. The hydrophilic monomer constituting the polymer swells upon contact with body fluids (e.g., blood, urine) or aqueous solvents, imparting slipperiness (lubricity) to the lubricating layer. Therefore, by incorporating such a hydrophilic monomer-derived structural unit A into the polymer, the lubricating layer formed using the polymer exhibits excellent slipperiness (lubricity) and can reduce friction when the medical device comes into contact with the wall of a biological lumen, such as a blood vessel wall. In this specification, the "hydrophilic monomer" is also referred to simply as the "hydrophilic monomer of the present invention" or "hydrophilic monomer." In this specification, the "hydrophilic monomer-derived structural unit A" is also referred to simply as the "structural unit A of the present invention" or "structural unit A." In this specification, the "polymer having a hydrophilic monomer-derived structural unit A" is also referred to simply as the "polymer of the present invention" or "polymer."

[0049] The hydrophilic monomer constituting the polymer may be any one that exhibits lubricity in body fluids or aqueous solvents.Preferably, the hydrophilic monomer is a material that exhibits a swelling rate of 200% or more when a lubricating layer is formed using a polymer having a structural unit A derived from the hydrophilic monomer.That is, in the present invention, the polymer having a structural unit A derived from the hydrophilic monomer is preferably a material that exhibits a swelling rate of 200% or more when the lubricating layer formed using the polymer exhibits a swelling rate of 200% or more.In addition, in this specification, the swelling rate of the lubricating layer is a value measured according to the method described in the following Examples [Measurement of Swelling Rate].

[0050] The polymer having the structural unit A derived from a hydrophilic monomer is preferably a material that exhibits a swelling rate of 500% or more when a lubricating layer is formed, and particularly preferably a material that exhibits a swelling rate of 800% or more when a lubricating layer is formed.Furthermore, the polymer having the structural unit A derived from a hydrophilic monomer is preferably a material that does not dissolve a part of the lubricating layer when wet.Therefore, the polymer having the structural unit A derived from a hydrophilic monomer is preferably a material that exhibits a swelling rate of less than 1500% when a lubricating layer is formed, and particularly preferably a material that exhibits a swelling rate of less than 1300% when a lubricating layer is formed.Therefore, the polymer having the structural unit A derived from a hydrophilic monomer is preferably a material that exhibits a swelling rate of 200% or more and less than 1500% when a lubricating layer is formed, more preferably a material that exhibits a swelling rate of 500% or more and less than 1500%, and particularly preferably a material that exhibits a swelling rate of 800% or more and less than 1300%.

[0051] That is, the swelling ratio of the lubricating layer according to the present invention is preferably 200% or more and less than 1500%, more preferably 500% or more and less than 1500%, and particularly preferably 800% or more and less than 1300%. Thus, when the swelling ratio of the lubricating layer is 200% or more, the lubricating layer can swell sufficiently when in contact with body fluids (e.g., blood, urine) or aqueous solvents, and the lubrication (slipperiness) is further improved. Furthermore, when the swelling ratio of the lubricating layer is less than 1500%, the lubricating layer can maintain sufficient film strength and its durability is further improved. Therefore, a lubricating layer with a swelling ratio within the above range further improves the balance between lubrication and durability.

[0052] Examples of such hydrophilic monomers include acrylic acid, acrylamide, methacrylamide, N-methylacrylamide, N-methylmethacrylamide, N,N-dimethylacrylamide (DMAA), N,N-dimethylmethacrylamide, N-ethylacrylamide, N-ethylmethacrylamide, N,N-diethylacrylamide (DEAA), N,N-diethylmethacrylamide, N,N-dimethylaminopropylacrylamide, N,N-dimethylaminopropylmethacrylamide, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminoethyl methacrylate, 2-acrylamido-2-methylpropanesulfonic acid, N-(2-hydroxyethyl)acrylamide, N-(2-hydroxypropyl)acrylamide, N-(2-hydroxybutyl)acrylamide, N-vinyl-2-pyrrolidone (1-vinyl-2-pyrrolidone) (VP), polyethylene glycol monoacrylate, polyethylene glycol monomethacrylate, alkoxypolyethylene glycol monoacrylate, and alkoxypolyethylene glycol monomethacrylate.Among these, from the viewpoints of further imparting lubricity to the lubricating layer, ease of synthesis, operability, etc., hydrophilic monomers include acrylic acid, acrylamide, N-methylacrylamide, N,N-dimethylacrylamide, N-ethylacrylamide, N,N-diethylacrylamide, N,N-dimethylaminopropylacrylamide, N,N-dimethylaminopropylmethacrylamide, 2-acrylamido-2-methylpropanesulfonic acid, N-(2-hydroxyethyl)acrylamide, N-(2-hydroxypropyl)acrylamide, N-(2-hydroxybutyl)acrylamide, N-vinyl-2-pyrrolidone, and polyethylene glycol monoacrylate. , polyethylene glycol monomethacrylate, alkoxy polyethylene glycol monoacrylate, and alkoxy polyethylene glycol monomethacrylate, more preferably at least one selected from the group consisting of acrylic acid, acrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, and N-vinyl-2-pyrrolidone, further preferably acrylamide, N,N-dimethylacrylamide, or N-vinyl-2-pyrrolidone, and particularly preferably N,N-dimethylacrylamide or N-vinyl-2-pyrrolidone. The hydrophilic monomer-derived structural unit A may be composed of only one of the above hydrophilic monomers, or may be composed of two or more of the above hydrophilic monomers in combination.

[0053] That is, in one embodiment of the present invention, the hydrophilic monomer-derived structural unit A is a structural unit derived from at least one monomer selected from the group consisting of acrylic acid, acrylamide, N-methylacrylamide, N,N-dimethylacrylamide, N-ethylacrylamide, N,N-diethylacrylamide, N,N-dimethylaminopropylacrylamide, N,N-dimethylaminopropylmethacrylamide, 2-acrylamido-2-methylpropanesulfonic acid, N-(2-hydroxyethyl)acrylamide, N-(2-hydroxypropyl)acrylamide, N-(2-hydroxybutyl)acrylamide, N-vinyl-2-pyrrolidone, polyethylene glycol monoacrylate, polyethylene glycol monomethacrylate, alkoxypolyethylene glycol monoacrylate, and alkoxypolyethylene glycol monomethacrylate. In one embodiment of the present invention, the hydrophilic monomer-derived structural unit A is a structural unit derived from at least one monomer selected from the group consisting of acrylic acid, acrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, and N-vinyl-2-pyrrolidone. In one embodiment of the present invention, the hydrophilic monomer-derived structural unit A is derived from acrylamide, N,N-dimethylacrylamide, or N-vinyl-2-pyrrolidone. In one embodiment of the present invention, the hydrophilic monomer-derived structural unit A is derived from N,N-dimethylacrylamide or N-vinyl-2-pyrrolidone.

[0054] The content (composition) of the structural unit A derived from a hydrophilic monomer constituting the polymer according to the present invention is preferably 80 mol% or more when the total of all structural units constituting the polymer is taken as 100 mol%. The content (composition) of the structural unit A may be 80 mol% or more but less than 100 mol%, or 90 mol% or more but less than 100 mol%, or even 100 mol%, when the total of all structural units constituting the polymer is taken as 100 mol%. That is, the polymer according to the present invention may be composed only of the structural unit A derived from a hydrophilic monomer, or may further have other structural units in addition to the structural unit A derived from a hydrophilic monomer.

[0055] (Other Structural Units) Examples of monomers (other monomers) constituting the other structural units include hydrophobic monomers having an epoxy group, which will be described in detail below, as well as 4-hydroxybutyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate, 2-hydroxybutyl(meth)acrylate, 6-hydroxyhexyl(meth)acrylate, 1,4-cyclohexanedimethanol mono(meth)acrylate, 1-chloro-2-hydroxypropyl(meth)acrylate, diethylene glycol mono(meth)acrylate, 1,6-hexanediol mono(meth)acrylate, pentaerythritol tri(meth)acrylate, dipenta ... Examples of other structural units include erythritol 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, adipic acid, glutaric acid, triethylene glycol, tripropylene glycol, etc. These other structural units may be composed of only one type of other monomer, or two or more types of other monomers.

[0056] (Constituent Unit B Derived from Hydrophobic Monomer Having an Epoxy Group) The polymer forming the lubricating layer is preferably a copolymer having, in addition to the constituent unit A derived from the hydrophilic monomer, a constituent unit B derived from a hydrophobic monomer having an epoxy group (hydrophobic monomer). That is, the lubricating layer according to the present invention preferably contains a copolymer having the constituent unit A derived from the hydrophilic monomer and the constituent unit B derived from a hydrophobic monomer having an epoxy group. In this specification, the "hydrophobic monomer having an epoxy group" is also simply referred to as the "hydrophobic monomer according to the present invention" or "hydrophobic monomer." In addition, in this specification, the "constituent unit B derived from a hydrophobic monomer having an epoxy group" is also simply referred to as the "constituent unit B according to the present invention" or "constituent unit B." In addition, in this specification, the "copolymer having the constituent unit A derived from a hydrophilic monomer and the constituent unit B derived from a hydrophobic monomer having an epoxy group" is also simply referred to as the "copolymer according to the present invention" or "copolymer."

[0057] The hydrophobic monomer constituting the copolymer according to the present invention has an epoxy group as a reactive group. When a copolymer incorporating a structural unit B (hydrophobic portion) derived from such a hydrophobic monomer having an epoxy group is irradiated with an electron beam, the molecular bonds of the hydrophobic portion (particularly the epoxy group) are preferentially cleaved by the energy of the electron beam, forming multiple radicals (crosslinking points). Therefore, when the copolymer is irradiated with an electron beam, the generated radicals react with the hydrophobic portion of the same copolymer or the hydrophobic portion of an adjacent copolymer, bonding the molecular chains of the copolymer at multiple locations. Therefore, when the lubricating layer containing the copolymer according to the present invention is irradiated with an electron beam, the copolymers form a crosslinked structure (three-dimensional network structure), thereby further improving the film strength of the lubricating layer. Furthermore, it is presumed that the formation of such a crosslinked structure in the lubricating layer forms the network structure and pores according to the present invention, or their formation is promoted. Although such a crosslinking reaction due to electron beam irradiation can also occur in the structural unit A (hydrophilic portion) derived from the hydrophilic monomer, the reaction is more likely to proceed in the hydrophobic portion (particularly the epoxy group). Therefore, from the viewpoint of easily controlling the network structure and pores in the lubricating layer of the present invention to have an appropriate structure, it is preferable that the lubricating layer contains a copolymer having a structural unit B derived from a hydrophobic monomer having an epoxy group.

[0058] In addition, when the copolymer is irradiated with ultraviolet (UV) light, the photopolymerization initiator absorbs ultraviolet light to form acidic species, and the acidic species open the hydrophobic site (particularly, epoxy group) to form oxonium cation.Therefore, when the copolymer is irradiated with ultraviolet light, the oxonium cation reacts with the hydrophobic site (particularly, epoxy group) in the same copolymer or the hydrophobic site (particularly, epoxy group) of an adjacent copolymer, and the molecular chains of the copolymer are bonded together at multiple locations.Therefore, when the lubricating layer containing the copolymer according to the present invention is irradiated with ultraviolet light, the copolymers form a crosslinked structure (three-dimensional network structure) with each other, and the film strength of the lubricating layer is further improved.In addition, it is presumed that, at this time, the network structure and pores according to the present invention are formed in the lubricating layer, or their formation is promoted, along with the formation of such a crosslinked structure. Although such a crosslinking reaction due to ultraviolet irradiation can occur in the structural unit A (hydrophilic portion) derived from the hydrophilic monomer due to the acidic species formed by the photopolymerization initiator, the reaction is more likely to proceed in the hydrophobic portion (especially the epoxy group). Therefore, from the viewpoint of easily controlling the network structure and pores in the lubricating layer according to the present invention to have an appropriate structure, it is preferable that the lubricating layer contains a copolymer having a structural unit B derived from a hydrophobic monomer having an epoxy group.

[0059] The hydrophobic monomer is not particularly limited as long as it has an epoxy group, and known compounds can be used. Among these, the hydrophobic monomer having 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-methylglycidyl acrylate, and β-methylglycidyl methacrylate, because this stabilizes the intramolecular radicals generated upon electron beam irradiation, facilitating the subsequent crosslinking reaction, and also stabilizes the active polymerizable species (such as oxonium cations) generated upon ultraviolet irradiation, facilitating the subsequent crosslinking reaction. Among these, glycidyl (meth)acrylate is more preferred, and glycidyl methacrylate is particularly preferred, considering its ability to further promote the crosslinking reaction and ease of production. The hydrophobic monomer-derived structural unit B may be composed of only one of the above hydrophobic monomers, or may be composed of two or more of the above hydrophobic monomers in combination.

[0060] That is, in one embodiment of the present invention, the structural unit B derived from a hydrophobic monomer having an epoxy group is a structural unit derived from at least one monomer selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl acrylate, and β-methylglycidyl methacrylate. In one embodiment of the present invention, the structural unit B derived from a hydrophobic monomer having an epoxy group is a structural unit derived from glycidyl acrylate or glycidyl methacrylate. In one embodiment of the present invention, the structural unit B derived from a hydrophobic monomer having an epoxy group is a structural unit derived from glycidyl methacrylate.

[0061] The copolymer may be a random copolymer having a structural unit A derived from a hydrophilic monomer and a structural unit B derived from a hydrophobic monomer having an epoxy group, or a block copolymer having a structural unit A derived from a hydrophilic monomer and a structural unit B derived from a hydrophobic monomer having an epoxy group. The copolymer is preferably a block copolymer (a block copolymer of a hydrophilic monomer and a hydrophobic monomer having an epoxy group) having a block formed from a hydrophilic monomer and a block formed from a hydrophobic monomer having an epoxy group. The block copolymer can further improve the swelling property of the lubricating layer due to the block formed from the hydrophilic monomer. Furthermore, the block copolymer can further improve the durability of the lubricating layer by increasing the probability of crosslinking between hydrophobic monomers when irradiated with active energy rays such as electron beams or ultraviolet rays due to the block formed from the hydrophobic monomer. Therefore, block copolymers can achieve better results in terms of the film strength and lubricity of the lubricating layer.

[0062] The ratio of the structural unit A derived from the hydrophilic monomer to the structural unit B derived from the hydrophobic monomer having an epoxy group in the copolymer is not particularly limited. Considering further improvements in lubricity (sliding properties, sliding properties) and durability (particularly sliding durability), the copolymer preferably contains the structural unit A derived from the hydrophilic monomer in a ratio of 5 to 70 moles per mole of the structural unit B derived from the hydrophobic monomer having an epoxy group. More preferably, the copolymer contains the structural unit A derived from the hydrophilic monomer in a ratio of 5 to 50 moles per mole of the structural unit B derived from the hydrophobic monomer having an epoxy group. Even more preferably, the copolymer contains the structural unit A derived from the hydrophilic monomer in a ratio of 8 to 40 moles per mole of the structural unit B derived from the hydrophobic monomer having an epoxy group. Particularly preferably, the copolymer contains the structural unit A derived from the hydrophilic monomer in a ratio of 10 to 35 moles per mole of the structural unit B derived from the hydrophobic monomer having an epoxy group. By ensuring that the ratio of the structural unit B derived from the hydrophobic monomer having an epoxy group to the structural unit A derived from the hydrophilic monomer in the copolymer is within the above range, the lubricating layer has high lubricity and can exhibit excellent sliding durability.

[0063] Alternatively, the content (composition) of the structural unit A derived from a hydrophilic monomer in the copolymer may be in the following form. For example, in one embodiment of the present invention, the content (composition) of the structural unit A derived from a hydrophilic monomer is 80 mol % or more and less than 100 mol % with respect to all structural units constituting the copolymer. In one embodiment of the present invention, the content (composition) of the structural unit A derived from a hydrophilic monomer is 90 to 99 mol % with respect to all structural units constituting the copolymer. When the content (composition) of the structural unit A derived from a hydrophilic monomer is within the above range, the lubricating layer can exhibit high lubricity.

[0064] In the copolymer according to the present invention, when the copolymer further contains another structural unit (structural unit C) in addition to the structural unit A derived from a hydrophilic monomer and the structural unit B derived from a hydrophobic monomer having an epoxy group, the total content of the structural unit A and the structural unit B is preferably 95 mol% or more (upper limit: less than 100 mol%) when the total of all structural units constituting the copolymer is 100 mol%. More preferably, the copolymer according to the present invention is substantially composed of the structural unit A and the structural unit B (the content of the structural unit C is more than 0 mol% and less than 5 mol%). In this form, the copolymer according to the present invention can improve the lubricity (surface lubricity) by the structural unit A and the durability (particularly, sliding durability) by the structural unit B in a well-balanced manner. More preferably, the copolymer according to the present invention (preferably a block copolymer) is composed only of the structural unit A and the structural unit B (the content of the structural unit C = 0 mol%). In addition, when another structural unit C is further contained in addition to the structural unit A and the structural unit B, examples of the monomer constituting the other structural unit C that can be contained in the copolymer include compounds other than the hydrophobic monomers having an epoxy group exemplified in the section above (Other structural units).

[0065] The copolymer having the above composition can be controlled by adjusting the charge ratio (molar ratio) of each monomer so that it falls within the above range. Therefore, the charge ratio (molar ratio) of the hydrophilic monomer to the hydrophobic monomer in the copolymer production stage is preferably within the above range.

[0066] The composition (molar ratio) of each structural unit of the copolymer can be determined, for example, by NMR measurement of the copolymer ( １ H-NMR measurement, １３ For example, the composition of each structural unit can be confirmed by measuring the composition of the copolymer solution. １ The composition (molar ratio) of each structural unit can be determined by measuring the integral ratio of the intensity of each signal in the H-NMR spectrum.

[0067] In one embodiment of the present invention, the polymer constituting the lubricating layer is selected from the group consisting of acrylic acid, acrylamide, N-methylacrylamide, N,N-dimethylacrylamide, N-ethylacrylamide, N,N-diethylacrylamide, N,N-dimethylaminopropylacrylamide, N,N-dimethylaminopropylmethacrylamide, 2-acrylamido-2-methylpropanesulfonic acid, N-(2-hydroxyethyl)acrylamide, N-(2-hydroxypropyl)acrylamide, N-(2-hydroxybutyl)acrylamide, N-vinyl-2-pyrrolidone, polyethylene glycol monoacrylate, polyethylene glycol monomethacrylate, alkoxypolyethylene glycol monoacrylate, and alkoxypolyethylene glycol monoacrylate. the copolymer is any one selected from the group consisting of: a polymer constituted only by a structural unit A derived from at least one hydrophilic monomer selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl acrylate, and β-methylglycidyl methacrylate; a copolymer constituted essentially by a structural unit A derived from the hydrophilic monomer and a structural unit B derived from at least one hydrophobic monomer selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl acrylate, and β-methylglycidyl methacrylate; and a copolymer constituted only by the structural unit A derived from the hydrophilic monomer and the structural unit B derived from the hydrophobic monomer. In one embodiment of the present invention, the polymer constituting the lubricating layer is any one selected from the group consisting of: a polymer composed only of a structural unit A derived from at least one hydrophilic monomer selected from the group consisting of acrylic acid, acrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, and N-vinyl-2-pyrrolidone; a copolymer essentially composed of a structural unit A derived from the hydrophilic monomer and a structural unit B derived from a hydrophobic monomer, such as glycidyl acrylate or glycidyl methacrylate; and a copolymer composed only of a structural unit A derived from the hydrophilic monomer and a structural unit B derived from the hydrophobic monomer.In one embodiment of the present invention, the polymer constituting the lubricating layer is any one selected from the group consisting of a polymer composed only of a structural unit A derived from acrylamide, N,N-dimethylacrylamide, or N-vinyl-2-pyrrolidone as a hydrophilic monomer; a copolymer essentially composed of the structural unit A derived from the hydrophilic monomer and a structural unit B derived from glycidyl acrylate or glycidyl methacrylate as a hydrophobic monomer; and a copolymer composed only of the structural unit A derived from the hydrophilic monomer and the structural unit B derived from the hydrophobic monomer. In one embodiment of the present invention, the polymer constituting the lubricating layer is any one selected from the group consisting of a polymer composed only of the structural unit A derived from N,N-dimethylacrylamide or N-vinyl-2-pyrrolidone as a hydrophilic monomer; a copolymer essentially composed of the structural unit A derived from the hydrophilic monomer and a structural unit B derived from glycidyl methacrylate as a hydrophobic monomer; and a copolymer composed only of the structural unit A derived from the hydrophilic monomer and the structural unit B derived from the hydrophobic monomer. In one embodiment of the present invention, the polymer constituting the lubricating layer is either a copolymer substantially composed of a structural unit A derived from N,N-dimethylacrylamide and a structural unit B derived from glycidyl methacrylate; or a copolymer composed only of a structural unit A derived from N,N-dimethylacrylamide and a structural unit B derived from glycidyl methacrylate.

[0068] The method for producing the polymer according to the present invention is not particularly limited, and known methods can be applied in the same manner or with appropriate modifications. Furthermore, the method for producing the copolymer according to the present invention is not particularly limited, and known methods can be applied in the same manner or with appropriate modifications. For example, when the copolymer according to the present invention is a block copolymer, it can be produced by applying a conventionally known polymerization method such as a living radical polymerization method, a polymerization method using a macroinitiator, or a polycondensation method. Of these, living radical polymerization methods or polymerization methods using a macroinitiator are preferably used because they allow for easy control of the molecular weight and molecular weight distribution of the structural units (portions) derived from hydrophobic monomers and the structural units (portions) derived from hydrophilic monomers. The living radical polymerization method is not particularly limited, and examples thereof include methods described in JP-A-11-263819, JP-A-2002-145971, JP-A-2006-316169, and the like, as well as atom transfer radical polymerization (ATRP), and the like, can be applied in the same manner or with appropriate modifications. Furthermore, in a polymerization method using a macroinitiator, for example, a hydrophobic monomer having an epoxy group and a macroinitiator having a radically polymerizable group such as a peroxide group are prepared, and then the macroinitiator, a hydrophilic monomer, and, if necessary, a polymerization initiator are polymerized in a polymerization solvent, thereby producing a block copolymer having a structural unit A derived from a hydrophilic monomer and a structural unit B derived from a hydrophobic monomer.

[0069] In preparing the copolymer, the mixing ratio of the hydrophilic monomer and the hydrophobic monomer is preferably controlled so as to obtain the above-mentioned composition. The polymerization solvent is appropriately selected from solvents in which each monomer can be dissolved. For example, water, dimethyl sulfoxide, chlorobenzene, tetrahydrofuran, etc. are used, with dimethyl sulfoxide, chlorobenzene, and tetrahydrofuran being preferred from the viewpoint of monomer solubility. The polymerization conditions are also not particularly limited as long as the copolymerization proceeds. For example, the polymerization temperature is preferably 30 to 150°C, more preferably 40 to 100°C. The polymerization time is preferably 30 minutes to 24 hours, more preferably 3 to 15 hours. The polymerization is preferably carried out in an inert atmosphere such as a nitrogen atmosphere or an argon atmosphere.

[0070] Furthermore, when producing the copolymer, chain transfer agents, polymerization rate modifiers, surfactants, water-soluble polymers, water-soluble inorganic compounds (such as alkali metal salts, alkali metal hydroxides, polyvalent metal salts, and non-reducing alkali metal salt pH buffers), inorganic acids, inorganic acid salts, organic acids, organic acid salts, and other additives may be used as appropriate, if necessary. After polymerization, the copolymer is preferably purified by a common purification method such as reprecipitation, dialysis, ultrafiltration, or extraction.

[0071] The weight-average molecular weight of the (co)polymer according to the present invention is preferably 10,000 to 10,000,000 from the viewpoint of solubility in a solvent. The weight-average molecular weight of the copolymer is more preferably 30,000 to 5,000,000, and particularly preferably 50,000 to 3,000,000, from the viewpoint of ease of preparation of a coating liquid. In this specification, the "weight-average molecular weight" is a value measured by gel permeation chromatography (GPC) using polystyrene as a standard substance.

[0072] As described below, the medical device according to the present invention can be produced by applying a coating liquid containing the polymer to a substrate layer and then irradiating the substrate with active energy rays. In this case, electron beams or ultraviolet (UV) rays can be used as the active energy rays. However, when crosslinking the polymer by electron beam irradiation, a photopolymerization initiator (e.g., a benzophenone-based photoinitiator or an acetophenone-based photoinitiator) is not required. Therefore, in one embodiment, the lubricating layer is preferably substantially free of photopolymerization initiators and their residues. Here, the phrase "the lubricating layer is substantially free of photopolymerization initiators and their residues" refers to a total content (in terms of solids content) of unreacted photopolymerization initiators and post-reaction photopolymerization initiator residues relative to the total mass of the lubricating layer (solid content) of less than 0.5% by mass (lower limit: 0%), preferably 0.1% by mass or less (lower limit: 0%), and more preferably 0% by mass (the lubricating layer is free of photopolymerization initiators and their residues). The fact that the lubricating layer is substantially free of photopolymerization initiators and their residues can be confirmed, for example, by pyrolysis GC-MS (gas chromatography-mass spectrometry).

[0073] Other Components The lubricating layer may contain other components in addition to the polymer. The other components are not particularly limited. For example, when the medical device is intended for insertion into a body cavity or lumen, such as a catheter, examples of the other components include anticancer drugs, immunosuppressants, antibiotics, antirheumatic drugs, antithrombotic drugs, HMG-CoA reductase inhibitors, ACE inhibitors, calcium channel blockers, antihyperlipidemic drugs, integrin inhibitors, antiallergic drugs, antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid-improving drugs, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet drugs, vascular smooth muscle proliferation inhibitors, anti-inflammatory drugs, biomaterials, interferons, and NO production promoters (biologically active substances). The amount of the other components added is not particularly limited, and commonly used amounts are used in the same manner. Ultimately, the amount of the other components added is appropriately selected by the attending physician, taking into account the severity of the disease to be treated, the patient's weight, and the like. Preferably, the lubricating layer is substantially free of other components (i.e., the lubricating layer is substantially composed of the polymer). Specifically, the content of other components is preferably less than 10% by mass (solid content equivalent) of the mass of the lubricating layer, more preferably less than 5% by mass (solid content equivalent), and it is particularly preferable that the lubricating layer is free of other components (i.e., the lubricating layer is composed of the polymer).

[0074] <<Needle-like crystals>> When observing the surface of the lubricating layer according to the present invention, it is preferable that there are few needle-like crystals on the surface.Specifically, it is preferable that the surface of the lubricating layer has less than 5 needle-like crystals with a length of 1 μm or more in an observation image at 5000 times magnification when the lubricating layer is swollen.Generally, when an operator delivers a medical device to a lesion site of a biological lumen (when the operator slides the medical device in the biological lumen), the surface of the lubricating layer and the surface of the biological lumen are repeatedly rubbed against each other, and therefore, a part of the lubricating layer (coating fragments) can peel off from the lubricating layer as fine particles. Therefore, particularly under harsh conditions where the lubricating layer surface and the wall of the biological lumen are likely to rub against each other (for example, when the medical device is repeatedly slid to deliver the medical device to the lesion site through a place where the bending radius of the biological lumen is small, a place where the bending section of the biological lumen is continuously present, or a place where the inner diameter of the biological lumen is narrow, etc.), when the medical device is operated, coating fragments peel off from the lubricating layer surface of the medical device, and the lubricating layer's lubrication maintenance (sliding durability) is likely to decrease.On the other hand, if the number of the above-mentioned needle-shaped crystals on the lubricating layer surface is less than 5, when the surgeon slides the medical device in the biological lumen, it can reduce the lubricating layer peeling from the needle-shaped crystals as a starting point, or the needle-shaped crystals themselves peeling off from the lubricating layer as coating fragments (fine particles).Therefore, under harsh conditions where the friction between the lubricating layer surface and the wall of the biological lumen increases, the lubricating layer's lubrication maintenance (sliding durability) can be further improved. From the viewpoint of further improving the lubrication maintenance (sliding durability) of the lubricating layer, in the observation image of the lubricating layer at 5000 times magnification when the lubricating layer is swollen, the number of needle-like crystals with a length of 1 μm or more observed on the surface of the lubricating layer is preferably 3 or less, more preferably 1 or less, and particularly preferably 0. Note that the number of the needle-like crystals is the number of needle-like crystals observed in the image observed by the method described in the section [SEM observation of lubricating layer (when swollen)] of Examples.

[0075] <<Thickness>> The thickness (dry film thickness) of the lubricating layer is, for example, about 0.1 to 10 μm, preferably about 0.3 to 5 μm, and more preferably about 0.5 to 3 μm.

[0076] <Sliding Resistance Value> As described above, the lubricating layer according to the present invention has excellent lubricity (slipperiness), and therefore has a low sliding resistance value when wet. Specifically, the sliding resistance value of the lubricating layer can be less than 20 gf as determined by sliding resistance value evaluation. Furthermore, the sliding resistance value of the lubricating layer as determined by sliding resistance value evaluation is preferably less than 10 gf, and more preferably 7.5 gf or less. Meanwhile, the lower limit of the sliding resistance value is not particularly limited, but can be, for example, 0.1 gf or more. The sliding resistance value is a value measured by the method described in the section "Sliding Durability Evaluation" in the Examples.

[0077] <Method for manufacturing a medical device> In the medical device according to the present invention, the surface of the lubricating layer has a network structure observed in an observation image of the lubricating layer during swelling and a plurality of pores surrounded by the network structure, and the network structure and pores satisfy the above-mentioned condition (1) or (2). Such a medical device can be manufactured, for example, by forming a coating film (precursor layer) containing a polymer on a substrate layer, and then irradiating the coating film (precursor layer) with active energy rays under specific conditions to form a lubricating layer on the substrate layer. By irradiating the coating film (precursor layer) containing a polymer with active energy rays, the polymer forms a crosslinked structure, thereby promoting the formation of the network structure and pores in the lubricating layer. In this case, by controlling the density of the crosslinked structure (crosslink density) according to the irradiation conditions of the active energy rays, the density of the network structure of the lubricating layer can be controlled, and thus the area of ​​each pore can also be controlled. Furthermore, a method of heating the coating film (precursor layer) under specific conditions can be used to form the lubricating layer, but from the viewpoint of production efficiency, a method using active energy rays is preferred.

[0078] The type and irradiation conditions of the active energy ray are not particularly limited as long as they can form a network structure and pores that satisfy the above condition (1) or (2).From the viewpoint of effectively promoting the crosslinking reaction of the polymer, it is preferable to use an electron beam or ultraviolet light as the active energy ray.

[0079] <<Formation of Lubricating Layer by Electron Beam Irradiation>> In one embodiment, the lubricating layer according to the present invention is preferably formed by irradiating a coating film (precursor layer) containing a polymer with an electron beam. That is, the lubricating layer is preferably formed by curing with an electron beam (curing a polymer with an electron beam). Forming the lubricating layer by electron beam irradiation is preferable from the viewpoint of production efficiency, since the polymers crosslink and harden in a short time. Furthermore, electron beam irradiation is performed at room temperature and does not require heating, so it can be suitably used for substrates with low heat resistance. Furthermore, as described below, when using ultraviolet irradiation, a photopolymerization initiator is used to efficiently carry out the crosslinking reaction. In this case, the photopolymerization initiator and its residue may remain in the lubricating layer. In contrast, when forming the lubricating layer by electron beam irradiation, a photopolymerization initiator is not required, and therefore the photopolymerization initiator and its residue are not contained in the lubricating layer, which is more preferable from the viewpoint of the biological safety required for medical devices.

[0080] Therefore, another aspect of the present invention provides a method for producing a medical device, comprising: applying a coating liquid containing a polymer having a structural unit A derived from a hydrophilic monomer and a solvent to at least a part of a base layer to form a precursor layer on at least a part of the base layer ((I) precursor layer forming step); and irradiating the precursor layer with an electron beam at an exposure dose of more than 0 kGy and less than 500 kGy to form a lubricating layer on the base layer that swells when contacted with an aqueous solvent ((II-1) electron beam irradiation step), wherein the surface of the lubricating layer has a network structure and a plurality of pores surrounded by the network structure in an observation image of the lubricating layer when swollen, and the network structure and the pores satisfy the following condition (1) or the following condition (2): (1) the pores have an average area of ​​1 μm in plan view. ２ or more, and the maximum area is 30 μm ２ (2) The pores have an average area of ​​1 μm or less in a plan view. ２ or more, and the maximum area is 30 μm ２ and the average mesh thickness of the mesh structure is 1 μm or more.

[0081] A preferred embodiment of each step will be described below. The explanations for the base layer, lubricating layer, network structure, pores, and the above conditions (1) and (2) are given in the above section <Medical Device>.

[0082] (I) Precursor Layer Formation Step In this step, a solution containing a polymer, a solvent, and, if necessary, other components (also referred to simply as a "coating liquid" in this specification) is prepared, and the coating liquid is applied to a substrate layer to form a precursor layer (coating film) on the substrate layer. The method for applying the solution is not particularly limited except for using a solution containing a polymer and a solvent, and can be applied in the same manner as a known method or by appropriately modifying it. Note that, when the coating liquid contains other components, the other components are the same as those described above, and therefore, description thereof will be omitted here.

[0083] First, a solution (coating liquid) containing a polymer and a solvent, and, if necessary, other components, is prepared. The solvent used to prepare the coating liquid is not particularly limited and is appropriately selected depending on the type of polymer (and other components, if used). From the viewpoint of high solubility, water, acetone, isopropyl alcohol (IPA), ethanol, methanol, dichloromethane, chloroform, carbon tetrachloride, tetrahydrofuran (THF), dimethyl sulfoxide, N,N-dimethylformamide, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, and the like are preferably used. The above solvents may be used alone or in the form of a mixed solvent of two or more kinds.

[0084] The concentration of the polymer in the coating solution is not particularly limited. For example, the concentration of the polymer in the coating solution is preferably 0.05 to 30% by mass, more preferably 1 to 25% by mass, and particularly preferably 3 to 20% by mass. If the polymer concentration is within the above range, the resulting lubricating layer can fully exhibit the effects of the present invention. Furthermore, a lubricating layer of the desired thickness can be easily obtained with a single coating, and the viscosity of the solution falls within an appropriate range, which is preferable in terms of operability (e.g., ease of coating) and production efficiency. However, even if the concentration is outside the above range, it can be fully used as long as it does not affect the effects of the present invention.

[0085] Next, the coating liquid prepared as described above is applied (coated) onto the substrate layer. Here, the substrate layer is the same as that described above, so a description thereof will be omitted here. Note that the substrate layer may be hydrophilized before the coating liquid is applied. Examples of methods for hydrophilizing the substrate layer include plasma treatment, electron beam irradiation treatment, and ultraviolet irradiation treatment. The conditions for the hydrophilization treatment are determined appropriately depending on the type of substrate layer.

[0086] The method for applying the coating liquid to the surface of the substrate layer is not particularly limited, and any conventionally known method can be used, such as coating / printing, immersion (dipping, dip coating), spraying (spraying), spin coating, mixed solution-impregnated sponge coating, bar coating (e.g., wire bar method), die coating, reverse coating, comma coating, gravure coating, doctor knife method, etc. Of these, immersion (dipping, dip coating), spraying (spraying), and bar coating are preferably used.

[0087] If it is difficult to immerse only a portion of the substrate layer in the coating liquid, the surface portion of the substrate layer that does not require the formation of a precursor layer can be protected (coated, etc.) with a suitable removable (attachable) member or material, and then the substrate layer can be immersed in the coating liquid to coat the substrate layer with the coating liquid. After that, the protective member (material) from the surface portion of the substrate layer that does not require the formation of a lubricating layer can be removed, thereby forming a precursor layer on the desired surface portion of the substrate layer. However, the present invention is not limited to these formation methods, and a precursor layer can be formed using any conventionally known method. For example, if it is difficult to immerse only a portion of the substrate layer in the coating liquid, other coating methods (e.g., methods in which the coating liquid is applied to a predetermined surface portion of a medical device using an application device such as a sprayer, bar coater, die coater, reverse coater, comma coater, gravure coater, spray coater, or doctor knife) can be used instead of the immersion method. Note that the immersion method (dipping method) is preferably used from the viewpoints of mass productivity and production control.

[0088] The amount of coating liquid to be applied is preferably selected so that the thickness of the resulting lubricating layer (dry film thickness) falls within the above range.

[0089] Next, the precursor layer formed above is dried if necessary to form a precursor layer on the substrate layer. The drying treatment includes natural drying or heat treatment, but natural drying is preferred. Furthermore, the conditions for heat treatment are not particularly limited as long as they allow the solvent to be removed (allowing the precursor layer to be formed on the substrate layer), and can be appropriately selected depending on the type of solvent. For example, the heat treatment temperature is preferably 10 to 50°C. Furthermore, the heat treatment time is preferably 1 minute to 5 hours. Under the above conditions, the solvent can be efficiently removed and the precursor layer can be formed on the substrate layer.

[0090] The pressure conditions in the drying step are not particularly limited, and the drying step may be carried out under normal pressure (atmospheric pressure), or may be under increased or reduced pressure. As the drying means (apparatus), for example, an oven or a reduced-pressure dryer can be used, but in the case of natural drying, no particular drying means (apparatus) is required.

[0091] (II-1) Electron Beam Irradiation Step In this step, the precursor layer formed in (I) above is irradiated with an electron beam under specific conditions to form a lubricating layer. Specifically, the precursor layer formed in (I) above is irradiated with an electron beam at an exposure dose of more than 0 kGy and less than 500 kGy to form a lubricating layer having a lubricating layer structure that satisfies the above condition (1) or the above condition (2).

[0092] In this process, the dose of the electron beam irradiated to the precursor layer is more than 0 kGy and less than 500 kGy. If the dose of the electron beam irradiated to the precursor layer is 500 kGy or more, the crosslinking reaction of the polymer will proceed excessively, resulting in a high crosslink density. As a result, the density of the network structure in the lubricating layer will increase and the area of ​​the pores will decrease, resulting in a decrease in the lubricity (slipperiness) of the lubricating layer.

[0093] Here, when the polymer constituting the lubricating layer (precursor layer) is the above-mentioned copolymer (a copolymer having a structural unit A derived from a hydrophilic monomer and a structural unit B derived from a hydrophobic monomer having an epoxy group), when irradiated with an electron beam, the molecular bonds of the hydrophobic portion (especially the epoxy group) are preferentially broken, and crosslinking proceeds. However, if the irradiation dose of the electron beam is large, the molecular bonds of the hydrophilic portion of the copolymer are also broken, which is thought to cause excessive crosslinking reaction. Therefore, when the polymer constituting the lubricating layer (precursor layer) is the above-mentioned copolymer, it is preferable to reduce the irradiation dose of the electron beam in order to suppress the excessive crosslinking reaction as described above and form an appropriate lubricating layer structure. Specifically, when the polymer constituting the lubricating layer (precursor layer) is the above-mentioned copolymer, the irradiation dose of the electron beam irradiated to the precursor layer is preferably less than 200 kGy, more preferably 100 kGy or less, even more preferably 100 kGy or less, particularly preferably 50 kGy or less, and most preferably 30 kGy or less. In addition, in this case, the molecular bond of the hydrophobic part (particularly, epoxy group) of the copolymer is broken by electron beam irradiation to form a plurality of radicals (crosslinking points) (to increase the film strength of the lubricating layer), so the irradiation dose of the electron beam irradiated to the precursor layer is more than 0 kGy, preferably more than 5 kGy, more preferably 10 kGy or more.Therefore, when the polymer constituting the lubricating layer (precursor layer) is the above-mentioned copolymer, the irradiation dose of the electron beam irradiated to the precursor layer is preferably more than 5 kGy and less than 200 kGy, more preferably more than 5 kGy and less than 100 kGy, even more preferably more than 5 kGy and less than 100 kGy, particularly preferably 10 kGy or more and 50 kGy or less, most preferably 10 kGy or more and 30 kGy or less.With such an irradiation dose, the molecular bond of the hydrophobic part (particularly, epoxy group) of the copolymer can be selectively and efficiently broken during electron beam irradiation to form radicals (crosslinking points), so that the crosslinking reaction of the copolymer can proceed with a moderate crosslinking density. As a result, a lubricating layer having an appropriate lubricating layer structure can be formed, and lubricity and durability are further improved.

[0094] When the polymer constituting the lubricating layer (precursor layer) is a polymer that does not contain a structural unit B derived from a hydrophobic monomer (for example, a polymer consisting only of a structural unit A derived from a hydrophilic monomer), the crosslinking reaction caused by the hydrophobic moiety (especially an epoxy group) as described above does not proceed, so it is necessary to form an appropriate lubricating layer structure by the crosslinking reaction of the hydrophilic moiety. Therefore, when the polymer constituting the lubricating layer (precursor layer) is a polymer that does not contain a structural unit B derived from a hydrophobic monomer, it is preferable to increase the electron beam irradiation dose in order to promote the crosslinking reaction of the hydrophilic moiety and form an appropriate lubricating layer structure. Specifically, when the polymer constituting the lubricating layer (precursor layer) is a polymer that does not contain a structural unit B derived from a hydrophobic monomer, the irradiation dose of the electron beam irradiated to the precursor layer is preferably more than 100 kGy, more preferably 200 kGy or more, even more preferably 300 kGy or more, and particularly preferably 350 kGy or more. In this case, the irradiation dose of the electron beam irradiated to the precursor layer may be less than 500 kGy and 450 kGy or less. Therefore, when the polymer constituting the lubricating layer (precursor layer) is a polymer that does not contain the structural unit B derived from a hydrophobic monomer, the electron beam irradiation dose to the precursor layer is preferably more than 100 kGy and less than 500 kGy, more preferably 200 kGy or more and less than 500 kGy, even more preferably 300 kGy or more and less than 500 kGy, and particularly preferably 350 kGy or more and 450 kGy or less. With such an irradiation dose, the molecular bonds of the hydrophilic parts of the polymer can be broken during electron beam irradiation to form radicals (crosslinking points), so that the crosslinking reaction of the polymer can proceed with a moderate crosslinking density. Specifically, with such an irradiation dose, during electron beam irradiation, some ethylene structures constituting the polymer main chain are radicalized, and reaction with radicals of the hydrophilic parts of the same polymer or radicals of the hydrophilic parts of adjacent polymers proceeds, so that the crosslinking reaction of the polymer can proceed with a moderate crosslinking density. As a result, a lubricating layer having an appropriate lubricating layer structure can be formed, and lubricity and durability can be further improved.

[0095] In this step, the electron beam irradiation conditions are appropriately selected depending on the type of polymer contained in the lubricating layer (precursor layer). For example, the irradiation temperature is preferably 10 to 80°C, more preferably 20 to 40°C. The acceleration voltage is preferably 50 to 200 kV, more preferably 50 to 70 kV. Furthermore, electron beam irradiation is preferably carried out in an inert atmosphere such as a nitrogen atmosphere or an argon atmosphere.

[0096] <<Formation of Lubricating Layer by Ultraviolet Irradiation>> In another embodiment, the lubricating layer according to the present invention may be formed by irradiating a coating film (precursor layer) containing a polymer with ultraviolet rays. When the lubricating layer is formed by ultraviolet irradiation, the coating liquid containing the polymer further contains a photopolymerization initiator.

[0097] Therefore, another aspect of the present invention provides a method for manufacturing a medical device, comprising: applying a coating liquid containing a polymer having a structural unit A derived from a hydrophilic monomer, a photopolymerization initiator, and a solvent to at least a portion of a base layer to form a precursor layer on at least a portion of the base layer ((I) precursor layer forming step); and irradiating the precursor layer with ultraviolet light to form a lubricating layer on the base layer that swells when contacted with an aqueous solvent ((II-2) ultraviolet light irradiation step), wherein the surface of the lubricating layer has a network structure and a plurality of pores surrounded by the network structure in an observation image of the lubricating layer when swelled, and the network structure and the pores satisfy the above condition (1) or the above condition (2).

[0098] A preferred embodiment of each step will be described below. The explanations for the base layer, lubricating layer, network structure, pores, and the above conditions (1) and (2) are given in the above section <Medical Device>.

[0099] (I) Precursor layer forming step In this step, a solution (also referred to as a coating liquid) containing a polymer, a photopolymerization initiator, and a solvent, as well as other components if necessary, is prepared, and the coating liquid is applied onto the substrate layer to form a precursor layer (coating film) on the substrate layer.

[0100] The photopolymerization initiator used in this case is not particularly limited, and known photopolymerization initiators can be used. Specific examples include carbonyl compounds such as benzophenone compounds, and photoreducible dyes. Of these, carbonyl compounds, particularly benzophenone compounds, are preferred. Examples of benzophenone compounds include, but are not limited to, benzophenone, xanthone, 9-fluorenone, 2,4-dichlorobenzophenone, methyl o-benzoylbenzoate, 4,4'-bis(dimethylamino)benzophenone, 4,4'-bis(diethylamino)benzophenone, disodium 5-bis[(4-benzoylbenzyl)oxy]benzene-1,3-disulfonate, 2,3,4,5,6-pentafluorobenzophenone, and decafluorobenzophenone. One type of photopolymerization initiator may be used alone, or two or more types may be used in combination. Of these, benzophenone or disodium 5-bis[(4-benzoylbenzyl)oxy]benzene-1,3-disulfonate is preferred as the photopolymerization initiator from the viewpoint of facilitating control of the crosslink density.

[0101] The amount of the photopolymerization initiator in the coating liquid is not particularly limited as long as the crosslinking reaction of the polymer proceeds sufficiently, but is preferably 0.01 to 10 parts by mass, more preferably 0.5 to 8 parts by mass, and particularly preferably 1 to 5 parts by mass, relative to 100 parts by mass of the polymer.

[0102] The concentration of the photopolymerization initiator in the coating solution is preferably adjusted so that the mass ratio of the polymer to the photopolymerization initiator falls within the above-mentioned preferred range. For example, the concentration of the photopolymerization initiator in the coating solution is preferably 0.005 to 10 mass%, and more preferably 0.05 to 5 mass%. If the concentration of the photopolymerization initiator is within the above-mentioned range, the crosslinking reaction of the polymer can be sufficiently promoted, and an appropriate lubricating layer structure can be formed. However, even if the concentration is outside the above-mentioned range, it can be used as long as it does not affect the effects of the present invention.

[0103] In this step, the explanation in the section <<Formation of Lubricating Layer by Electron Beam Irradiation>> is applicable, except that the coating liquid contains a photopolymerization initiator.

[0104] (II-2) Ultraviolet Light Irradiation Step In this step, the precursor layer formed in (I) above is irradiated with ultraviolet light to form a lubricating layer. In this specification, "ultraviolet light" refers to electromagnetic waves having a wavelength of 10 to 400 nm. The wavelength of the irradiated ultraviolet light is, for example, 100 to 400 nm, and more preferably 200 to 400 nm. Examples of means for generating such ultraviolet light include metal halide lamps, high-pressure mercury lamps, low-pressure mercury lamps, mercury-xenon lamps, xenon arc lamps, carbon arc lamps, and excimer lamps.

[0105] In this step, the conditions for irradiating the precursor layer with ultraviolet light are not particularly limited, but it is preferable to set the illuminance and irradiation time so as to promote the crosslinking reaction of the polymer.

[0106] For example, the illuminance of ultraviolet light is 0.1 to 100 mW / cm ２ It is preferable that the power is 1 to 50 mW / cm ２ More preferably, it is 3 to 10 mW / cm ２ It is particularly preferable that the irradiation amount (integrated light amount) of ultraviolet light is, for example, 300 to 3000 mJ / cm ２ and 500 to 1000 mJ / cm ２ The irradiation time is preferably set so as to achieve the above-mentioned preferred integrated light amount, for example, 1 second to 30 minutes, preferably 1 to 5 minutes.

[0107] By the above method, a medical device having a lubricating layer with excellent lubricity and durability can be produced.

[0108] [Uses of Medical Devices] The lubricating layer of the medical device according to the present invention has excellent lubricity and durability. Therefore, when the medical device according to the present invention is used in contact with body fluids, blood, etc., the surface has lubricity in body fluids or aqueous liquids such as physiological saline, which can improve operability and reduce damage to tissue mucosa. Specific examples of the medical device include catheters, stents, guidewires, etc. used in blood vessels. That is, in one embodiment of the present invention, the medical device is a catheter, stent, or guidewire. Other examples of the medical device include the following:

[0109] (a) Catheters inserted or left in the digestive tract via the mouth or nose, such as gastric catheters, nutritional catheters, and tube feeding tubes; (b) Catheters inserted or left in the airway or trachea via the mouth or nose, such as oxygen catheters, oxygen cannulas, endotracheal tube tubes and cuffs, tracheostomy tube tubes and cuffs, and endotracheal suction catheters; (c) Catheters inserted or left in the urethra or ureter, such as urethral catheters, urinary catheters, and urethral balloon catheter catheters and balloons; (d) Catheters inserted or left in various body cavities, organs, and tissues, such as suction catheters, drainage catheters, and rectal catheters; (e) Catheters inserted or left in blood vessels, such as indwelling needles, IVH catheters, thermodilution catheters, angiography catheters, vasodilator catheters, and dilators or introducers, or guide wires, stylets, etc. for these catheters; (f) artificial tracheas, artificial bronchi, etc. (g) Medical devices for extracorporeal circulation therapy (artificial lungs, artificial hearts, artificial kidneys, etc.) and their circuits.

[0110] The effects of the present invention will be explained using the following examples and comparative examples. However, the technical scope of the present invention is not limited to the following examples, and examples obtained by appropriately combining the technical means disclosed in each example are also included in the scope of the present invention. In the following examples, unless otherwise specified, operations were performed at room temperature (25°C). Furthermore, unless otherwise specified, "%" and "parts" mean "% by mass" and "parts by mass", respectively.

[0111] [Preparation of Coated Samples] Synthesis Example 1: Synthesis of Block Copolymer (p(DMAA-GMA)(12 / 1)) 29.7 g of triethylene glycol was added dropwise to 72.3 g of adipic acid dichloride at 50°C, and then the hydrochloric acid was removed under reduced pressure at 50°C over 3 hours to obtain 22.5 g of oligoester. 4.5 g of methyl ethyl ketone was added to the obtained 22.5 g of oligoester, and this 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, and 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. Subsequently, 0.5 g of PPO as a polymerization initiator and 9.5 g of glycidyl methacrylate (GMA) as a hydrophobic monomer were polymerized in benzene as a solvent at 65°C for 2 hours while stirring under reduced pressure. The product obtained after the polymerization was reprecipitated with diethyl ether to obtain polyGMA (PPO-GMA) having peroxide groups in the molecule.

[0112] Next, 1.35 g of PPO-GMA (corresponding to 9.5 mmol of GMA) as a polymerization initiator and 11.2 g (113 mmol) of N,N-dimethylacrylamide (DMAA) as a hydrophilic monomer were dissolved in chlorobenzene, and the mixture was heated to 80°C for 7 hours under a nitrogen atmosphere to polymerize. The resulting product was reprecipitated with cyclohexane and recovered to prepare a block copolymer having a DMAA moiety as a hydrophilic moiety and a GMA moiety as a hydrophobic moiety. The DMAA:GMA ratio (molar ratio) of the prepared block copolymer was １ Measurement by H-NMR confirmed that the DMAA:GMA ratio (i.e., the molar ratio of hydrophilic moieties to hydrophobic moieties in the block copolymer) was 12:1. The weight-average molecular weight (Mw) of the block copolymer was 1,000,000. Hereinafter, the block copolymer will also be referred to as "p(DMAA-GMA)(12 / 1)."

[0113] Example 1 Coating liquid 1 was prepared by dissolving the block copolymer (p(DMAA-GMA)(12 / 1)) obtained in Synthesis Example 1 in acetone to a concentration of 9% by mass.

[0114] Next, a core bar (outer diameter approximately 0.6 mm) was inserted into a tube substrate (inner diameter 0.6 mm) made of polyamide elastomer (Grilflex® ELG6260, manufactured by EMS) (nylon elastomer) with an outer diameter of 1.00 mm. The prepared coating solution 1 was then dip-coated at a rate of 5 mm / sec to form a precursor layer. After air drying, the precursor layer (coated surface) was irradiated with an electron beam using an electron beam irradiation device (manufactured by Hamamatsu Photonics K.K., EB-ENGINE® L12978) under conditions of an accelerating voltage of 60 kV and an exposure dose of 10 kGy in a nitrogen gas atmosphere to obtain Coated Sample 1. In the obtained Coated Sample 1, a lubricating layer (dry film thickness: approximately 1 μm) containing a block copolymer (p(DMAA-GMA)(12 / 1)) was formed on the tube substrate.

[0115] Example 2 Coated sample 2 was obtained in the same manner as in Example 1, except that the electron beam irradiation dose was changed to 30 kGy.

[0116] Example 3 Coated sample 3 was obtained in the same manner as in Example 1, except that the dose of electron beam irradiation was changed to 100 kGy.

[0117] Example 4 Poly(N,N-dimethylacrylamide) (pDMAA) (homopolymer of N,N-dimethylacrylamide, manufactured by Scientific Polymer, weight average molecular weight (Mw) = 100,000) was dissolved in acetone to a concentration of 20 mass % to prepare coating liquid 2.

[0118] Next, a core bar (outer diameter approximately 0.6 mm) was inserted into a tube substrate (inner diameter 0.6 mm) made of polyamide elastomer (Grilflex® ELG6260, manufactured by EMS) (nylon elastomer) with an outer diameter of 1.00 mm. The prepared coating solution 2 was then dip-coated at a rate of 5 mm / sec to form a precursor layer. After air drying, the precursor layer (coated surface) was irradiated with an electron beam using an electron beam irradiation device (manufactured by Hamamatsu Photonics K.K., EB-ENGINE® L12978) under conditions of an accelerating voltage of 60 kV and an exposure dose of 400 kGy in a nitrogen gas atmosphere to obtain coated sample 4. In the obtained coated sample 4, a lubricating layer (dry film thickness: approximately 1 μm) containing polyDMAA (pDMAA) was formed on the tube substrate.

[0119] Example 5 Polyvinylpyrrolidone (PVP) (homopolymer of 1-vinyl-2-pyrrolidone (VP), manufactured by Tokyo Chemical Industry Co., Ltd., Polyvinylpyrrolidone K90, weight average molecular weight (Mw) = 360,000) was dissolved in a mixed solvent of water and isopropyl alcohol (IPA) (water:IPA = 9:1 (volume ratio)) to a concentration of 4 mass %. Disodium 4,5-bis[(4-benzoylbenzyl)oxy]benzene-1,3-disulfonate (manufactured by Tokyo Chemical Industry Co., Ltd.) was dissolved in this mixture to a concentration of 0.1 mass % to prepare coating solution 3.

[0120] Next, the outer surface of a tube substrate made of polyamide elastomer (Grilflex (registered trademark) ELG6260, manufactured by EMS) (nylon elastomer) with an outer diameter of 1.00 mm (inner diameter of 0.6 mm) was irradiated with an electron beam in a nitrogen gas atmosphere at an acceleration voltage of 50 kV and an irradiation dose of 200 kGy to hydrophilize the substrate surface. A core metal (outer diameter approximately 0.6 mm) was inserted into this tube substrate, and the hydrophilized substrate surface of this tube substrate was dip-coated with the coating liquid 3 prepared above at a speed of 10 mm / sec to form a precursor layer. After air drying, the dip-coated tube substrate was rotated at 200 rpm, and the precursor layer (coated surface) was coated with 6 mW / cm ２ for 2 minutes at an illuminance of 720 mJ / cm ２), and coated sample 5 was obtained. At this time, EXECURE (registered trademark) 4000 (manufactured by HOYA Corporation) and surface irradiation unit HLL-Q1 (manufactured by HOYA Corporation) were used for UV irradiation. In the obtained coated sample 5, a lubricating layer (dry film thickness: approximately 2 μm) containing polyvinylpyrrolidone (PVP) was formed on the tube substrate.

[0121] Comparative Example 1 A coated sample 6 was obtained in the same manner as in Example 1, except that the electron beam irradiation dose in Example 1 was not carried out.

[0122] Comparative Example 2 Coated sample 7 was obtained in the same manner as in Example 1, except that the dose of electron beam irradiation was changed to 5 kGy.

[0123] Comparative Example 3 A coated sample 8 was obtained in the same manner as in Example 1, except that the dose of electron beam irradiation was changed to 200 kGy.

[0124] Comparative Example 4 Coated sample 9 was obtained in the same manner as in Example 1, except that the dose of electron beam irradiation was changed to 500 kGy.

[0125] The swelling ratio of the lubricating layer was measured for the coated samples 1 to 9 obtained in the above examples and comparative examples according to the following method. The results are shown in Table 2 below.

[0126] [Measurement of Swelling Ratio] The swelling ratio of the lubricating layer was calculated using the following formula.

[0127] Swelling rate of lubricating layer (%) = [Swelled film thickness (μm) / Dry film thickness (μm)] × 100 Swelled film thickness (μm) = [(External diameter of specimen when swollen (μm) - External diameter of specimen before swelling (μm))] / 2.

[0128] In the above formula, the dry film thickness of the lubricating layer was measured using a Filmetrics microfilm thickness measurement system (F40, software FILMesure (manufactured by Filmetrics Inc.)). The coated sample was fixed on the stage of the microfilm thickness measurement system, and the film thickness (μm) of the lubricating layer was measured in an environment adjusted to a humidity of 30% RH or less using dry air. The film thickness was also measured at points rotated 90 degrees, 180 degrees, and 270 degrees from the initial measurement surface, and the average value of the four points was taken as the dry film thickness (μm) of the sample.

[0129] In the above formula, the specimen outer diameter was measured using a laser diameter measuring device (LASER SCAN MCROMETER LS, manufactured by KEYENCE). The coated sample was immersed in RO water for 1 minute, and the outer diameter of the coated sample was measured before and after immersion. The measurement length was 50 mm, and measurements were taken at 0.5 mm intervals. The average of these measurements was used as the measured outer diameter (μm) of the coated sample. Note that, when calculating the average, obvious noise not caused by the coating, such as foreign matter adhesion, was excluded. Furthermore, if at least a portion of the coated sample dissolved during swelling ratio measurement and could not be measured, it was judged as "partially dissolved." In the above formula, "specimen outer diameter (μm) before swelling" refers to the measured outer diameter of the coated sample before immersion in RO water, and "specimen outer diameter (μm) upon swelling" refers to the measured outer diameter of the coated sample after immersion in RO water for 1 minute.

[0130] The substrate materials, (co)polymers of the lubricating layers, and curing methods of the lubricating layers (electron beam irradiation conditions, etc.) for coated samples 1 to 9 obtained in the above examples and comparative examples are summarized in Table 2 below. In Table 2 below, the notation "EB 'a' kGy ('b' kV)" for the curing method indicates that the electron beam irradiation dose was 'a' (kGy) and the acceleration voltage was 'b' (kV). For example, the electron beam irradiation conditions in Example 1 indicate an acceleration voltage of 60 kV and an irradiation dose of 10 kGy. In Comparative Example 4, since no network structure was observed in the SEM observation described below, "average hole area," "maximum hole area," "average mesh thickness," and "maximum area / average mesh thickness" are indicated with "-" in Table 2 below.

[0131] [SEM Observation of Lubricating Layer (When Swelled)] For coated samples 1 to 9 obtained in the above examples and comparative examples, the lubricating layer surface when swollen was observed using a scanning electron microscope (SEM) according to the following procedure: 1. Each coated sample was cut to a length of approximately 15 mm to obtain a surface observation sample (tube substrate). The surface observation sample was immersed in RO water for 5 minutes or more to swell the lubricating layer. At this time, RO water was also injected into the lubricating layer sample's inner cavity (the lumen of the tube substrate) with a syringe so that the surface observation sample was submerged in the RO water; 2. The surface observation sample was removed from the RO water and quickly fixed to an LV (low vacuum) cooling holder (manufactured by JEOL Ltd.) with carbon tape; 3. RO water was dripped onto the surface of the surface observation sample fixed to the cooling holder so that the entire surface observation sample was covered with RO water; 4. The LV cooling holder was quickly immersed in liquid nitrogen and left for about 5 minutes; 5. The LV cooling holder was removed from the liquid nitrogen and quickly introduced into an SEM (JSM-IT800SHL manufactured by JEOL Ltd.) whose chamber vacuum had been set to 30 Pa in advance in LV mode; 6. The sample was left in the SEM for about 1 hour to allow the frozen water (RO water that had been poured to cover the surface observation sample and frozen) to sublimate; 7. The LV cooling holder was removed from the SEM, and the surface observation sample was fixed to a normal SEM sample stage; 8. An osmium coat (film thickness: approximately 4 nm) was applied to the surface observation sample using an osmium coater (HPC-20 manufactured by Vacuum Device Co., Ltd.); 9. The outer surface of the surface observation sample was observed with an SEM at a field of view of 5000x in high vacuum mode (approximately E-3 to E-4 Pa).

[0132] SEM images (5000x magnification) obtained by the above SEM observation are shown in Figures 1 to 9. As a result of the SEM observation, no needle-shaped crystals (needle-shaped crystals of 1 μm or more) were observed in the 5000x observation images for any of the samples (the number of needle-shaped crystals was 0). Here, needle-shaped crystals may contribute to an increase in fine particles (coating debris) that shed from the surface of the lubricating layer when the medical device slides. According to the medical device and manufacturing method for the medical device of the present invention, the generation of needle-shaped crystals is suppressed, and therefore it can be said that the effect of significantly reducing fine particles (coating debris) that may shed from the surface of the lubricating layer is also achieved.

[0133] [Analysis of Network Structure] For coated samples 1 to 9, the network structure (mesh thickness, pore area, etc.) of the lubricating layer was analyzed based on the SEM images (5000x magnification) obtained by the above procedure. The analysis of pores and mesh thickness was performed as follows. The results are shown in Table 2 below. In the above [SEM observation of lubricating layer (swollen)], the lubricating layer of the surface observation sample that had undergone freeze-drying was observed. The lubricating layer of the surface observation sample was maintained in the swollen state due to freeze-drying during SEM observation. Therefore, in the above [SEM observation of lubricating layer (swollen)], the network thickness and pore area (average area, maximum area) of the lubricating layer after freeze-drying did not change from those of the lubricating layer when swollen. Therefore, the analysis results of the network structure (mesh thickness, pore area, etc.) based on the SEM images obtained by the above procedure were used as the analysis results of the network structure of the lubricating layer when swollen.

[0134] (Pore Analysis) Using image processing software (ImageJ; US National Institutes of Health), the pore size in the SEM image (5000x magnification) was analyzed according to the following procedure to determine the average and maximum pore area: 1. Open the SEM image (5000x magnification) to be analyzed, and select the area excluding the measurement conditions and scale bar of the SEM image (specifically, the area of ​​the SEM image shown in Figures 1 to 9). This selected area was used as the analysis area (19.2 μm (vertical) × 25.6 μm (horizontal)). 2. Next, select Adjust and Threshold in the Image tab, and then click the Apply button to create a binarized image of the pores (black) and the network structure (white). The resulting binarized image (corresponding to the SEM image of Example 2) is shown in Figure 10. 3. Next, reselect the analysis area selected in step 1 above, and click Find Edges in the Process tab to perform edge processing on the boundary between the pores and the network structure. An example of the image after the edge processing for the SEM image in Figure 10 is shown in Figure 11. 4. Next, select Analyze Particles in the Analyze tab and click the OK button to analyze particles with a size of 0.1 μm. ２ The above pore analysis was performed. Other analysis conditions in Analyze Particles were selected as follows: Size: 0.10-Infinity (μm 2 ) ・Circularity: 0.00-1.00 ・Show: Outlines ・Other checked items -Display results -Clear results -Add to Manager -Include holes -Overlay 5. From the above analysis results, the average area and maximum area of ​​the holes were calculated.

[0135] (Mesh Thickness Analysis) 1. The steps up to edge processing in step 3 of the hole analysis were carried out in the same manner to create an image after edge processing. 2. The image after edge processing was divided into nine sections (divided into 3 rows x 3 columns), and the dimensions (mesh thickness) between holes (mesh structure) in each section were measured at any one point within each section (9 points in total). 3. The arithmetic mean of the mesh thicknesses within each section obtained in step 3 above was calculated, and this was used as the average mesh thickness.

[0136] [Sensory Evaluation] Sensory evaluation was carried out on the coated samples 1 to 9 obtained in the above examples and comparative examples according to the following procedure. The results are shown in Table 2 below.

[0137] The lubricating layers (coated surfaces) of coated samples 1 to 9 were immersed in RO water. After 1 minute, while still immersed in water, the lubricating layer was pinched with the pads of the fingers and rubbed with the pads of the fingers 30 times over a width of approximately 5 cm in the longitudinal direction of the sample. The slipperiness (lubricity) and durability were evaluated based on the evaluation criteria in Table 1 below. The slipperiness (lubricity) was categorized based on the feel after the second rub using the following evaluation criteria, and durability was categorized based on the change in slipperiness after 30 rubs. The rubbing strength and speed were kept as similar as possible between samples.

[0138]

[0139] [Evaluation of sliding durability] The sliding durability (lubrication maintenance ability) of the coated samples 1 to 9 obtained in the above examples and comparative examples was evaluated according to the following method. The results are shown in the "OR 20 times (gf)" section of Table 2 below.

[0140] In the evaluation, the sliding resistance value of the lubricating layer of each coated sample was measured using an Oakriver sliding tester (DL1000, manufactured by OAKRIVER TECHNOLOGY A PaR Systems Company) according to the following procedure.

[0141] The container was filled with RO water, and each coated sample was fixed to the Oak River sliding tester so that the measurement point of the lubricating layer (coated surface) was immersed in the RO water. After immersing the coated sample in RO water for 1 minute, a pair of silicone terminals (13 mm x 32 mm) of the Oak River sliding tester were brought close to each other and set to clamp the measurement point of the coated sample with a load of 500 gf. Next, while applying a grip force of 500 gf with the silicone terminals, the coated sample was moved at a sliding distance of 50 mm and a sliding speed of 10 mm / sec, and the same location of the coated sample was repeatedly slid vertically 20 times. The sliding resistance value (gf) was measured when the sample was pulled up vertically on the 20th attempt. Before measuring the sliding resistance value, a core was inserted into the inner cavity of the coated sample (tube substrate).

[0142]

[0143] The results in Table 2 show that coated samples 3 to 5, 8 and 9 of the examples are able to achieve both lubricity (sliding properties) and durability compared to coated samples 1, 2, 6 and 7 of the comparative examples.

[0144] First, the relationship between the analysis results of the network structure and each evaluation result was examined as follows: While the coated samples 6 and 7 of Comparative Examples 3 and 4 did not provide sufficient lubricity (sliding property), the other coated samples provided sufficient lubricity (sliding property). This is because the lubricating layers of Comparative Examples 3 and 4 (coated samples 6 and 7) had an average pore area of ​​1 μm ２ (In coated sample 7, as shown in Figure 7, the network structure is so densely formed that it is not visible in the 5000x observation image, and it appears that no network structure is formed.) In such cases, it is thought that a sufficient amount of water (water molecules) cannot be taken into the pores, making it difficult to swell. In contrast, in all coated samples other than coated samples 6 and 7, the average area of ​​the pores is 1 μm ２ As a result, a sufficient amount of water (water molecules) can be captured in the pores, and as a result, the lubricating layer has good swelling properties and can exhibit excellent lubricity (sliding properties).

[0145] Furthermore, although the lubricating layers of coated samples 1 and 2 of Comparative Examples 1 and 2 exhibited good lubricity (slipperiness), the sensory evaluation of durability showed that the lubricating layers peeled off quickly, indicating poor durability. In contrast, the other coated samples (coated samples 3 to 9) produced lubricating layers with good durability. This is because coated samples 1 and 2 had relatively large maximum pore areas (30 μm ２ This is thought to be because the lubricating layer easily absorbs water (water molecules) due to the large diameter of the holes, resulting in excellent lubrication (slipperiness), but the average mesh thickness of the network structure is less than 1 μm, which is too thin, making the network structure susceptible to breaking due to sliding, resulting in a decrease in the durability of the lubricating layer. ２ When the mesh thickness exceeds 1 μm, it has been found that by making the average mesh thickness 1 μm or more (i.e., satisfying condition (2)), not only the lubricity (slidability) of the lubricating layer but also its durability can be improved.

[0146] Furthermore, although the average mesh thickness of coated samples 5 and 6 in Example 3 and Comparative Example 3 was less than 1 μm, these coated samples also exhibited good durability. This is because the maximum area of ​​the pores in both coated samples 5 and 6 was relatively small (30 μm ２ ) the mesh structure is thought to be densely formed, and in such a case, it is presumed that a lubricating layer with sufficient durability is formed even if the mesh thickness itself is thin. (However, as mentioned above, in Comparative Example 3 (coated sample 6), the average area of ​​the pores is 1 μm ２ Since the content is less than 100%, good lubricity (slipperiness) cannot be obtained.)

[0147] Furthermore, comparing coated samples 3 to 5 of Examples 1 to 3 in Table 2, coated samples 3 and 4 are superior in lubricity (sliding property) and durability (especially superior in lubricity) compared to coated sample 5. From these results, it is believed that a relatively large maximum area of ​​the pores and a thick mesh thickness enable the lubricating layer to exhibit good durability while maintaining excellent lubricity (sliding property). In other words, it can be said that satisfying condition (2) is more preferable than condition (1) according to the present invention.

[0148] Next, the conditions for forming the lubricating layer (curing method) were considered as follows: Coated samples 1 to 7 were produced under similar conditions except for the electron beam irradiation conditions during curing. As shown in Table 2 and Figures 1 to 7, when the lubricating layer was cured by electron beam irradiation, the mesh thickness of the network structure increased as the irradiation dose increased, and it was found that the mesh thickness tended to decrease around 100 kGy after exceeding 30 kGy. When forming the lubricating layer by electron beam irradiation, as the electron beam irradiation dose to the precursor layer (coated surface) increased, the crosslinking reaction caused by the epoxy groups (epoxy groups derived from GMA) contained in the copolymer (p(DMAA-GMA)(12 / 1)) increased, and the crosslink density of the lubricating layer increased. For this reason, when the electron beam irradiation dose to the precursor layer (coated surface) is 100 kGy, the crosslinking reaction caused by the epoxy groups (epoxy groups derived from GMA) contained in the copolymer (p(DMAA-GMA)(12 / 1)) increases compared to when the electron beam irradiation dose to the precursor layer (coated surface) is 10 kGy or 30 kGy, which is thought to increase the crosslink density of the lubricating layer and reduce the average area and maximum area of ​​the pores. Therefore, it is thought that the average mesh thickness also decreases with this increase in crosslink density of the lubricating layer. Furthermore, when the electron beam irradiation dose to the precursor layer (coated surface) is 0 kGy or 5 kGy, the crosslinking reaction caused by the epoxy groups (epoxy groups derived from GMA) contained in the copolymer (p(DMAA-GMA)(12 / 1)) does not progress sufficiently compared to when the electron beam irradiation dose to the precursor layer (coated surface) is 10 kGy, which is thought to result in a low crosslink density of the lubricating layer and therefore a small average mesh thickness.

[0149] Furthermore, when the electron beam irradiation dose to the precursor layer (coated surface) is greater than 100 kGy, the crosslinking reaction of the copolymer further increases, further increasing the crosslink density of the lubricating layer. Therefore, when the electron beam irradiation dose to the precursor layer (coated surface) is 500 kGy, the average area of ​​the pores on the surface of the lubricating layer is further reduced in an observation image at 5000 times magnification when the lubricating layer is swollen, and it is presumed that the surface becomes smooth upon observation.

[0150] Therefore, by taking such a tendency into consideration and appropriately adjusting the amount of electron beam irradiation, it is possible to control the area and mesh thickness of the holes in the mesh structure of the lubricating layer.

[0151] Furthermore, in coated sample 8 of Example 4, the polymer (DMAA homopolymer) forming the lubricating layer does not contain epoxy groups, unlike the copolymer (p(DMAA-GMA)(12 / 1)). Therefore, although intramolecular and / or intermolecular crosslinking reactions due to electron beam irradiation also occur in coated sample 8, the reactivity is low (lower than that of epoxy groups), and therefore, it is believed that the electron beam irradiation dose required to form an appropriate lubricating layer structure is greater than when the copolymer is used. Increasing the electron beam irradiation dose on the precursor layer (coated surface) may cause damage to the substrate layer. Therefore, coated samples 3 to 5 of Examples 1 to 3 are preferable compared to coated sample 8 of Example 4, because they are able to cure the polymer in the precursor layer (coated surface) with a lower electron beam irradiation dose.

[0152] Furthermore, coated sample 9 of Example 5 was cured by UV irradiation, and like electron beam irradiation, it was able to form an appropriate network structure, resulting in a lubricating layer with excellent lubricity (sliding properties) and durability. Coated sample 9 of Example 5 requires a photopolymerization initiator when curing the polymer in the precursor layer (coated surface). Therefore, coated sample 9 of Example 5 may leave unreacted photopolymerization initiator or photopolymerization initiator residue in the lubricating layer. Therefore, compared to coated sample 9 of Example 5, coated samples 3 to 5 of Examples 1 to 3 are preferable from the perspective of the biological safety required for medical devices because they are able to cure the copolymer in the precursor layer (coated surface) without using a photopolymerization initiator.

[0153] This application is based on Japanese Patent Application No. 2024-052926 filed on March 28, 2024 and Japanese Patent Application No. 2025-046740 filed on March 21, 2025, the disclosures of which are incorporated herein by reference in their entireties.

Claims

1. A medical device comprising: a base layer; and a lubricating layer supported on at least a portion of the base layer and which swells when in contact with an aqueous solvent, wherein the lubricating layer contains a polymer having a structural unit A derived from a hydrophilic monomer, and the surface of the lubricating layer has a network structure and a plurality of pores surrounded by the network structure in an observation image of the lubricating layer when swollen, and the network structure and the pores satisfy the following condition (1) or (2): (1) the pores have an average area of ​​1 μm in a plan view ２ or more, and the maximum area is 30 μm ２ (2) The pores have an average area of ​​1 μm or less in a plan view. ２ or more, and the maximum area is 30 μm ２ and the average mesh thickness of the mesh structure is 1 μm or more.

2. The pores have an average area of ​​1 to 10 μm in plan view. ２ and the ratio of the maximum area of ​​the hole to the average mesh thickness of the mesh structure (the maximum area of ​​the hole (unit: μm ２ 2. The medical device according to claim 1, wherein the ratio of the number of meshes per unit area (unit: μm) to the average mesh thickness of the mesh structure (unit: μm) is 20 to 50.

3. The pores have an average area of ​​3 to 10 μm in plan view. ２ The medical device according to claim 1 , 4. The pores have an average area of ​​3 to 10 μm in plan view. ２ and the maximum area is 30 μm ２ Over 100 μm ２ or less, and the ratio of the maximum area of ​​the hole to the average mesh thickness of the mesh structure (the maximum area of ​​the hole (unit: μm ２ 2. The medical device according to claim 1, wherein the ratio of the number of meshes per unit area (unit: μm) to the average mesh thickness of the mesh structure (unit: μm) is 20 to 50.

5. The medical device according to claim 1, wherein the surface of the lubricating layer has less than five needle-shaped crystals with a length of 1 μm or more in an image observed at 5000 times when the lubricating layer is swollen.

6. The medical device according to claim 1, wherein the hydrophilic monomer-derived structural unit A is a structural unit derived from at least one monomer selected from the group consisting of acrylic acid, acrylamide, N-methylacrylamide, N,N-dimethylacrylamide, N-ethylacrylamide, N,N-diethylacrylamide, N,N-dimethylaminopropylacrylamide, N,N-dimethylaminopropylmethacrylamide, 2-acrylamido-2-methylpropanesulfonic acid, N-(2-hydroxyethyl)acrylamide, N-(2-hydroxypropyl)acrylamide, N-(2-hydroxybutyl)acrylamide, N-vinyl-2-pyrrolidone, polyethylene glycol monoacrylate, polyethylene glycol monomethacrylate, alkoxypolyethylene glycol monoacrylate, and alkoxypolyethylene glycol monomethacrylate.

7. The medical device according to claim 1, wherein the lubricating layer comprises a copolymer having a structural unit A derived from the hydrophilic monomer and a structural unit B derived from a hydrophobic monomer having an epoxy group.

8. The medical device according to claim 7, wherein said structural unit B derived from a hydrophobic monomer having an epoxy group is a structural unit derived from at least one monomer selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl acrylate, and β-methylglycidyl methacrylate.

9. The medical device according to claim 7, wherein the copolymer contains 5 to 50 moles of the structural unit A derived from the hydrophilic monomer per mole of the structural unit B derived from the hydrophobic monomer having an epoxy group.

10. The medical device according to claim 1, wherein the sliding resistance value of the lubricating layer is evaluated to be less than 20 gf.

11. The medical device according to claim 1, wherein the lubricating layer does not contain a photopolymerization initiator and its residue.

12. The medical device according to claim 1, wherein the lubricating layer is formed by curing with an electron beam.

13. The medical device of claim 1, wherein the medical device is a catheter, a stent, or a guidewire.

14. A method for manufacturing a medical device, comprising: applying a coating liquid containing a polymer having a structural unit A derived from a hydrophilic monomer and a solvent to at least a portion of a substrate layer to form a precursor layer on at least a portion of the substrate layer; and irradiating the precursor layer with an electron beam at an exposure dose of more than 0 kGy and less than 500 kGy to form a lubricating layer on the substrate layer that swells when contacted with an aqueous solvent, wherein the surface of the lubricating layer has a network structure and a plurality of pores surrounded by the network structure in an observation image of the lubricating layer when swollen; and wherein the network structure and the pores satisfy the following condition (1) or the following condition (2): (1) the pores have an average area of ​​1 μm in a plan view. ２ or more, and the maximum area is 30 μm ２ (2) The pores have an average area of ​​1 μm or less in a plan view. ２ or more, and the maximum area is 30 μm ２ and the average mesh thickness of the mesh structure is 1 μm or more.

15. The manufacturing method according to claim 14, wherein the precursor layer is irradiated with electron beams at a dose of more than 5 kGy and less than 200 kGy.

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