Medical instrument and method for producing same

Abstract

The present invention provides: a medical instrument having a lubricating layer exhibiting good lubricity and improved in durability (especially sliding durability); and a method for producing the same.　The medical instrument according to the present invention comprises a base material layer and a lubricating layer formed on at least a part of the base material layer, wherein the lubricating layer contains a copolymer having a constituent unit derived from a hydrophilic monomer and a constituent unit derived from a hydrophobic monomer having an epoxy group, the swelling ratio of the lubricating layer is greater than 210% and less than 1350%, the lubricating layer has an uneven surface, and the arithmetic mean roughness (Sa) of the surface is less than 1.6 nm.

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 view of the above circumstances, and aims to provide a medical device having a lubricating layer that exhibits good lubricity and improved durability (particularly sliding durability), and a method for producing 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 controlling the swelling ratio and surface roughness of a lubricating layer containing a copolymer having specific structural units within specific ranges, thereby completing the present invention.

[0010] That is, the above-mentioned object can be achieved by (1) a medical device comprising a substrate layer and a lubricating layer formed on at least a part of the substrate layer, wherein the lubricating layer contains a copolymer having constitutional units derived from a hydrophilic monomer and constitutional units derived from a hydrophobic monomer having an epoxy group, the swelling ratio of the lubricating layer is more than 210% and less than 1350%, the lubricating layer has an irregular surface, and the arithmetic mean roughness (Sa) of the surface is less than 1.6 nm. (2) In the medical device of (1), the hydrophilic monomer is preferably made of a material whose homopolymer of the hydrophilic monomer has a gel fraction of less than 25% by mass at 250 kGy. (3) In the medical device of (1) or (2) above, the structural unit derived from the hydrophilic monomer is preferably a structural unit derived from at least one monomer selected from the group consisting of acrylamide, N-methylacrylamide, N,N-dimethylacrylamide (DMAA), N-ethylacrylamide, N,N-diethylacrylamide (DEAA), 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. (4) In the medical device of any one of (1) to (3) above, the structural unit derived from the hydrophobic monomer having an epoxy group is preferably a structural unit derived from at least one monomer 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.(5) In any of the medical devices (1) to (4), the copolymer preferably contains 5 to 50 moles of structural units derived from the hydrophilic monomer per mole of structural units derived from the hydrophobic monomer having an epoxy group. (6) In any of the medical devices (1) to (5), the arithmetic mean roughness (Sa) of the surface of the lubricating layer is preferably 0.55 nm or less. (7) In any of the medical devices (1) to (6), the maximum peak height (Sp) of the surface of the lubricating layer is preferably 7.2 nm or less. (8) In any of the medical devices (1) to (7), the swelling ratio of the lubricating layer is preferably 215% or more and 1150% or less. (9) In any of the medical devices (1) to (8), the sliding resistance value of the lubricating layer, as determined by a sliding resistance value evaluation, is preferably less than 20 gf. (10) In the medical device of any one of (1) to (9) above, the copolymer is a block copolymer having a block formed from a hydrophilic monomer and a block formed from a hydrophobic monomer having an epoxy group, and it is preferable that the region forming the convex portions on the surface of the lubricating layer contains more structural units derived from the hydrophobic monomer than the region forming the concave portions on the surface of the lubricating layer, and that the region forming the concave portions contains more structural units derived from the hydrophilic monomer than the region forming the convex portions. (11) In the medical device of any one of (1) to (10) above, it is preferable that the medical device is a catheter, a stent, or a guidewire.

[0011] The above object can also be achieved by (12) a method for producing a medical device, comprising: applying a coating liquid containing a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, 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 1000 kGy to form a lubricating layer having a swelling ratio of more than 210% and less than 1350%.

[0012] Alternatively, the above object can also be achieved by (13) a method for producing a medical device, comprising: applying a coating liquid containing a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, 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 under irradiation conditions represented by the following formula (1) to form a lubricating layer: 0.6<a×b≦27.0 Formula (1) In the above formula (1), a is the electron beam irradiation dose (kGy) and is less than 1000 kGy, and b is the composition (mol / mol) of the structural units derived from the hydrophobic monomer having an epoxy group relative to all structural units constituting the copolymer. (14) In the production method of (12) or (13) above, it is preferable that the irradiation dose is less than 500 kGy.

[0013] One aspect of the present invention relates to a medical device comprising a base layer and a lubricating layer formed on at least a portion of the base layer, wherein the lubricating layer contains a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, the swelling ratio of the lubricating layer is greater than 210% and less than 1350%, the lubricating layer has an uneven surface, and the arithmetic mean roughness (Sa) of the surface is less than 1.6 nm.

[0014] Another aspect of the present invention relates to a method for producing a medical device, comprising: applying a coating liquid containing a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, 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 1000 kGy to form a lubricating layer having a swelling ratio of more than 210% and less than 1350%.

[0015] Yet another aspect of the present invention relates to a method for producing a medical device, comprising: applying a coating liquid containing a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, 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 under irradiation conditions defined by the following formula (1) to form a lubricating layer: 0.6<a×b≦27.0 Formula (1) In the above formula (1), a is the electron beam irradiation dose (kGy) and is greater than 0 kGy and less than 1000 kGy, and b is the composition (mol / mol) of the structural units derived from the hydrophobic monomer having an epoxy group relative to all structural units constituting the copolymer.

[0016] With this configuration, it is possible to provide a medical device having a lubricating layer (coating layer) that exhibits good lubricity and has improved durability (especially sliding durability).

[0017] In this specification, the "hydrophobic monomer having an epoxy group" is also referred to simply as the "hydrophobic monomer" or the "hydrophobic monomer according to the present invention." The "copolymer having constitutional units derived from a hydrophilic monomer and constitutional units derived from a hydrophobic monomer having an epoxy group" is also referred to simply as the "copolymer" or the "copolymer according to the present invention."

[0018] As used herein, the range "X to Y" includes X and Y and means "X or more and Y or less." As used herein, the term "(meth)acrylic" encompasses both acrylic and methacrylic. Furthermore, "X and / or Y" means at least one of X and Y, and encompasses X alone, Y alone, and a combination of X and Y. Thus, for example, the term "(meth)acrylic acid" encompasses both acrylic acid and methacrylic acid. Similarly, the term "(meth)acrylate" encompasses both acrylate and methacrylate. Thus, for example, the term "glycidyl (meth)acrylate" encompasses both glycidyl acrylate and glycidyl methacrylate.

[0019] 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.

[0020] 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.

[0021] <Medical Device> A medical device according to one embodiment of the present invention comprises a substrate layer and a lubricating layer formed on at least a portion of the substrate layer. The lubricating layer comprises a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group. The lubricating layer exhibits a swelling ratio of more than 210% and less than 1350%. The lubricating layer has an irregular surface, and the arithmetic mean roughness (Sa) of the surface is less than 1.6 nm. Because the arithmetic mean roughness (Sa) of the lubricating layer surface of a medical device having the above configuration is less than 1.6 nm (due to the small irregularities on the lubricating layer surface), damage to the lubricating layer surface due to contact with the surface of a biological lumen during sliding can be reduced, and excellent lubrication maintenance (sliding durability) can be achieved. Furthermore, because the swelling ratio of the lubricating layer of a medical device having the above configuration is more than 210% and less than 1350%, the lubricating layer can exhibit excellent lubricity while maintaining its film strength when swelled. Therefore, a medical device having the above configuration can exhibit excellent lubricity and 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 bending portions, a portion of a biological lumen with a narrow inner diameter, etc.). Therefore, according to the present invention, a medical device having a lubricating layer that exhibits good lubricity and improved durability (particularly sliding durability), and a method for producing the same can be provided.

[0022] 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.

[0023] 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.

[0024] [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.

[0025] 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.

[0026] 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.

[0027] The shape of the substrate layer is not particularly limited, and may be selected appropriately depending on the mode of use, such as a sheet, a wire, or a tube.

[0028] [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, guide wires, etc., which are used, the entire surface (whole surface) of these medical devices does not necessarily need to have lubricity when wet, and only the surface part (sometimes a part or sometimes the whole) that is required to have lubricity when wet is provided with the lubricating layer.Therefore, the lubricating layer includes the form of being formed to cover only one entire side of the substrate layer; the form of being formed to cover both sides of the substrate layer; the form of being formed to cover parts of both sides of the substrate layer in the same or different forms; the form of being formed to cover part of one side of the substrate layer, etc.

[0029] The lubricating layer has a swelling ratio of more than 210% and less than 1350%. Here, if the swelling ratio of the lubricating layer is 210% or less, the lubricating layer will not swell sufficiently when in contact with body fluids (e.g., blood, urine) or aqueous solvents, resulting in poor lubricity (slipperiness). If the swelling ratio of the lubricating layer is 1350% or more, the lubricating layer will have excellent lubricity (slipperiness), but will not maintain sufficient film strength and will have poor durability. The swelling ratio of the lubricating layer is preferably 215% or more, more preferably 300% or more, even more preferably more than 500%, and particularly preferably 750% or more. The swelling ratio of the lubricating layer is preferably 1200% or less, more preferably less than 1200%, even more preferably 1150% or less, and particularly preferably 1130% or less. In one embodiment of the present invention, the swelling ratio of the lubricating layer is 215% or more and less than 1200%. In one embodiment of the present invention, the swelling ratio of the lubricating layer is 215% or more and less than 1200%. In one embodiment of the present invention, the swelling ratio of the lubricating layer is 215% or more and 1150% or less. In one embodiment of the present invention, the swelling ratio of the lubricating layer is 300% or more and 1150% or less. In one embodiment of the present invention, the swelling ratio of the lubricating layer is more than 500% and 1150% or less. In one embodiment of the present invention, the swelling ratio of the lubricating layer is 750% or more and 1130% or less. A lubricating layer with such a swelling ratio has an even better balance between lubricity and durability.

[0030] In this specification, the swelling ratio of the lubricating layer is a value measured according to the method described in the "Measurement of Swelling Ratio" section of the Examples below.

[0031] The lubricating layer has an uneven surface, and the arithmetic mean roughness (Sa) of the lubricating layer surface is less than 1.6 nm. The arithmetic mean roughness (Sa) of the lubricating layer surface is the arithmetic mean roughness of the lubricating layer surface in air (temperature 15 to 25°C, relative humidity 20 to 60% RH).

[0032] If the arithmetic mean roughness (Sa) of the lubricating layer surface is 1.6 nm or more, when the surgeon delivers the medical device to the lesion site of the biological lumen (when the surgeon slides the medical device in the biological lumen), the repeated rubbing of the lubricating layer surface with the biological lumen surface will easily cause a part of the lubricating layer (coating fragments) to peel off from the lubricating layer as fine particles.Therefore, particularly under severe conditions where the rubbing between the lubricating layer surface and the biological lumen wall increases (for example, when the medical device is repeatedly slid to deliver the medical device to the lesion site through the area where the bending radius of the biological lumen is small, the area where the bending part of the biological lumen is continuously present, the area where the inner diameter of the biological lumen is narrow, etc.), when operating the medical device, the coating fragments from the lubricating layer surface of the medical device will peel off, and the lubrication maintenance (sliding durability) of the lubricating layer will be easily reduced.In addition, the peeling of the coating fragments from the lubricating layer surface may lead to embolism caused by the coating fragments, and it is also required to suppress the peeling of the coating fragments (fine particles) caused by rubbing. Therefore, the arithmetic mean roughness (Sa) of the surface of the lubricating layer is preferably 1.0 nm or less, more preferably 0.65 nm or less, even more preferably 0.55 nm or less, and particularly preferably less than 0.55 nm (lower limit: 0 nm). With such an arithmetic mean roughness (Sa) of the surface of the lubricating layer, when an operator slides a medical device in a biological lumen, peeling of coating pieces (fine particles) from the lubricating layer due to repeated rubbing between the lubricating layer surface and the biological lumen surface can be more effectively prevented. Therefore, under harsh conditions where rubbing between the lubricating layer surface and the biological lumen wall increases, the lubrication maintenance (sliding durability) of the lubricating layer can be further improved.

[0033] In this specification, the arithmetic mean roughness (Sa) of the surface of the lubricating layer represents the arithmetic mean (nm) of the absolute value of the difference in height from a reference surface (average surface) of each measurement point (convex and concave portions) in an observation range (3 μm long x 3 μm wide) of the surface of the cleaned lubricating layer after swelling, drying, and cleaning the lubricating layer, and represents the variation in height when the height of the reference surface in that observation range is set to 0. As described above, the arithmetic mean roughness (Sa) of the surface of the lubricating layer is measured on the lubricating layer surface in air (temperature 15 to 25 ° C, relative humidity 20 to 60% RH). Specifically, the arithmetic mean roughness (Sa) of the surface of the lubricating layer is a value measured according to the method described in the "Surface Roughness Evaluation" section of the Examples below.

[0034] From the viewpoint of reducing wear of the lubricating layer (peeling of coating pieces from the lubricating layer) during sliding of the medical device and improving the lubrication maintenance (sliding durability) of the lubricating layer, it is preferable that the height of the convex portions present in the lubricating layer be as small as possible. Specifically, the maximum peak height (Sp) of the surface of the lubricating layer is preferably 7.2 nm or less, more preferably 7.1 nm or less, even more preferably 4.0 nm or less, and particularly preferably 3.0 nm or less (lower limit: 0 nm). With such a maximum peak height (Sp) of the surface of the lubricating layer, wear of the lubricating layer (peeling of coating pieces from the lubricating layer) during sliding of the medical device can be more effectively prevented, and the lubricating maintenance (sliding durability) of the lubricating layer can be further improved. Therefore, under harsh conditions where abrasion between the lubricating layer surface and the biological lumen wall increases, the lubricating maintenance (sliding durability) of the lubricating layer can be further improved.

[0035] In this specification, the maximum peak height (Sp) of the surface of the lubricating layer represents the distance from the reference surface (average surface) to the highest measurement point (protrusion) in an observation range (3 μm long x 3 μm wide) of the surface of the cleaned lubricating layer after swelling, drying, and cleaning the lubricating layer. The maximum peak height (Sp) of the surface of the lubricating layer, like the arithmetic mean roughness (Sa) of the surface of the lubricating layer, is measured under conditions of the lubricating layer surface in air (temperature 15 to 25°C, relative humidity 20 to 60% RH). Specifically, the maximum peak height (Sp) of the surface of the lubricating layer is a value measured according to the method described in the "Surface Roughness Evaluation" section of the Examples below.

[0036] The lubricating layer contains a copolymer having constitutional units derived from a hydrophilic monomer and constitutional units derived from a hydrophobic monomer having an epoxy group.

[0037] The hydrophilic monomer constituting the copolymer swells when in contact with body fluids (e.g., blood, urine) or aqueous solvents, imparting slipperiness (lubricity) to the lubricating layer. Therefore, by introducing structural units derived from such hydrophilic monomers into the copolymer, the lubricating layer formed using the copolymer exhibits excellent slipperiness (lubricity), thereby reducing friction when the medical device comes into contact with the wall of a biological lumen, such as a blood vessel wall. Specifically, the sliding resistance value of the lubricating layer as determined by sliding resistance value evaluation is less than 25 gf, preferably less than 20 gf, more preferably less than 18.0 gf, even more preferably less than 14.0 gf, and particularly preferably less than 12.0 gf. The "sliding resistance value as determined by sliding resistance value evaluation of the lubricating layer" is the sliding resistance value (gf) at the 20th time measured according to the method described in the "Sliding Durability Evaluation" section of the Examples below.

[0038] The hydrophilic monomer may be any one that exhibits lubricity in body fluids or aqueous solvents. Preferably, the hydrophilic monomer is a material that does not significantly or completely crosslink between constituent units derived from the hydrophilic monomer when the copolymer of the present invention is irradiated with an electron beam at a dose less than a predetermined dose. Therefore, the hydrophilic monomer is preferably a material that does not significantly or completely crosslink between homopolymers of the hydrophilic monomer when a homopolymer of the hydrophilic monomer is irradiated with an electron beam at a dose less than a predetermined dose. Specifically, the hydrophilic monomer is preferably composed of a material that produces a gel fraction of less than 25% by mass at 250 kGy. That is, the hydrophilic monomer is preferably composed of a material that produces a gel fraction of less than 25% by mass when a homopolymer of the hydrophilic monomer is irradiated with an electron beam at a dose of 250 kGy. The gel fraction is a value measured according to the method described in the "Gel Fraction Measurement" section of the Examples below.

[0039] Examples of such hydrophilic monomers include 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, and 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 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. Preferably, the structural unit derived from a hydrophilic monomer contains at least one selected from the group consisting of polyethylene glycol monomethacrylate, alkoxypolyethylene glycol monoacrylate, and alkoxypolyethylene glycol monomethacrylate, more preferably contains at least one selected from the group consisting of 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 structural unit derived from a hydrophilic monomer may be composed of only one type of the hydrophilic monomer, or may be composed of two or more types of the hydrophilic monomers in combination.

[0040] That is, in one embodiment of the present invention, the constitutional unit derived from a hydrophilic monomer is a constitutional unit derived from at least one monomer selected from the group consisting of 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 constitutional unit derived from a hydrophilic monomer is a constitutional unit derived from at least one monomer selected from the group consisting of acrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, and N-vinyl-2-pyrrolidone. In one embodiment of the present invention, the constitutional unit derived from a hydrophilic monomer is derived from acrylamide, N,N-dimethylacrylamide, or N-vinyl-2-pyrrolidone. In one embodiment of the present invention, the constitutional unit derived from a hydrophilic monomer is derived from N,N-dimethylacrylamide or N-vinyl-2-pyrrolidone.

[0041] The copolymer has a structural unit derived from a hydrophobic monomer having an epoxy group (hydrophobic monomer) in addition to the structural unit derived from the hydrophilic monomer.

[0042] The hydrophobic monomer constituting the copolymer has an epoxy group as a reactive group. When a copolymer incorporating a structural unit (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 broken 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 together at multiple locations. Therefore, when the lubricating layer containing the copolymer of the present invention is irradiated with an electron beam, the copolymers form a three-dimensional network structure, improving the film strength of the lubricating layer. In this case, the copolymers in the lubricating layer are crosslinked and hardened in a short time by the electron beam irradiation, thereby reducing the unevenness of the lubricating layer surface.

[0043] Furthermore, when the lubricating layer is formed on a substrate layer made of a resin material, radicals generated from the copolymer upon electron beam irradiation can react with the molecular chains of the resin material to form bonds, thereby further improving the durability of the lubricating layer when formed on a substrate layer made of a resin material.

[0044] The hydrophobic monomer constituting the copolymer 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 and facilitates 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 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.

[0045] That is, in one embodiment of the present invention, the structural unit 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 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 derived from a hydrophobic monomer having an epoxy group is a structural unit derived from glycidyl methacrylate.

[0046] The copolymer may be a random copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, or a block copolymer having structural units derived from a hydrophilic monomer and structural units 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 due to the block formed from the hydrophobic monomer having an epoxy group, which increases the probability of crosslinking between hydrophobic monomers upon electron beam irradiation. Therefore, block copolymers can achieve better results in terms of the film strength and lubricity of the lubricating layer. Furthermore, the epoxy group, a reactive functional group, forms a radical (crosslinking point) upon electron beam irradiation and reacts with adjacent hydrophobic monomers to form a crosslinked structure within the copolymer or between adjacent copolymers, further increasing the film strength of the lubricating layer.

[0047] The copolymer has the structural units derived from the hydrophilic monomer and the structural units derived from the hydrophobic monomer having an epoxy group. Here, the ratio of the structural units derived from the hydrophilic monomer to the structural units derived from the hydrophobic monomer having an epoxy group is not particularly limited. Considering further improvement in lubricity (slipperiness, sliding properties) and durability (particularly sliding durability), the copolymer preferably contains structural units derived from the hydrophilic monomer at a ratio of 5 moles or more, more preferably 10 moles or more, and particularly preferably 12 moles or more per mole of structural units derived from the hydrophobic monomer having an epoxy group. Furthermore, the copolymer preferably contains structural units derived from the hydrophilic monomer at a ratio of 70 moles or less, more preferably 50 moles or less, even more preferably 40 moles or less, and particularly preferably 35 moles or less per mole of structural units derived from the hydrophobic monomer having an epoxy group. In one embodiment of the present invention, the copolymer contains structural units derived from the hydrophilic monomer at a ratio of 5 moles or more to 70 moles or less per mole of structural units derived from the hydrophobic monomer having an epoxy group. In one embodiment of the present invention, the copolymer contains structural units derived from hydrophilic monomers in a ratio of 5 to 50 moles per mole of structural units derived from hydrophobic monomers having epoxy groups. In one embodiment of the present invention, the copolymer contains structural units derived from hydrophilic monomers in a ratio of 10 to 40 moles per mole of structural units derived from hydrophobic monomers having epoxy groups. In one embodiment of the present invention, the copolymer contains structural units derived from hydrophilic monomers in a ratio of 12 to 35 moles per mole of structural units derived from hydrophobic monomers having epoxy groups. When the copolymer contains structural units derived from hydrophilic monomers in the above ratio relative to structural units derived from hydrophobic monomers having epoxy groups, the lubricating layer can exhibit excellent sliding durability and high lubricity.

[0048] Alternatively, the content (composition) of the structural units derived from hydrophilic monomers is preferably 80 mol% or more, more preferably 90 mol% or more, relative to all structural units constituting the copolymer. Furthermore, the content (composition) of the structural units derived from hydrophilic monomers is preferably less than 100 mol%, more preferably 99 mol% or less, relative to all structural units constituting the copolymer. In one embodiment of the present invention, the content (composition) of the structural units derived from hydrophilic monomers is 80 mol% or more and less than 100 mol% relative to all structural units constituting the copolymer. In one embodiment of the present invention, the content (composition) of the structural units derived from hydrophilic monomers is 90 mol% or more and 99 mol% or less, relative to all structural units constituting the copolymer. When the content (composition) of the structural units derived from hydrophilic monomers is within the above range, the lubricating layer can exhibit high lubricity.

[0049] (Other Structural Units) The copolymer according to the present invention essentially contains a structural unit derived from a hydrophilic monomer and a structural unit derived from a hydrophobic monomer having an epoxy group, but may contain other structural units in addition to these structural units. When the copolymer contains other structural units, examples of the monomers (other monomers) constituting the other structural units include 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, dipentaerythritol tri(meth)acrylate, and the like. Examples of the other constituent units include butyl methyl ether, ...

[0050] When the copolymer according to the present invention has other structural units, the content of the other structural units is preferably more than 0 mol% and less than 5 mol% relative to the total structural units constituting the copolymer. That is, in the copolymer according to the present invention, when the total of all structural units constituting the copolymer is taken as 100 mol%, the total content of structural units derived from hydrophilic monomers and structural units derived from hydrophobic monomers having epoxy groups is preferably 95 mol% or more (upper limit: less than 100 mol%). More preferably, the copolymer according to the present invention is substantially composed of structural units derived from hydrophilic monomers and structural units derived from hydrophobic monomers having epoxy groups (content of other structural units = more than 0 mol% and less than 5 mol%). In this form, the copolymer according to the present invention can achieve a good balance between lubricity (surface lubricity) due to the structural units derived from hydrophilic monomers and durability (particularly sliding durability) due to the structural units derived from hydrophobic monomers having epoxy groups. Preferably, the copolymer according to the present invention (preferably a block copolymer) is composed only of structural units derived from hydrophilic monomers and structural units derived from hydrophobic monomers having epoxy groups (content of other structural units = 0 mol%).

[0051] 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.

[0052] 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.

[0053] In one embodiment of the present invention, the copolymer of the present invention is a copolymer of 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, alkoxypoly and at least one hydrophobic 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, or alternatively, the polymerizable composition is composed solely of the hydrophilic monomer-derived structural unit and the hydrophobic monomer-derived structural unit. In one embodiment of the present invention, the copolymer according to the present invention is substantially composed of structural units derived from at least one hydrophilic monomer selected from the group consisting of acrylamide, N,N-dimethylacrylamide, N,N-diethylacrylamide, and N-vinyl-2-pyrrolidone, and structural units derived from glycidyl acrylate or glycidyl methacrylate as a hydrophobic monomer, or is composed only of structural units derived from the hydrophilic monomer and structural units derived from glycidyl acrylate or glycidyl methacrylate.In one embodiment of the present invention, the copolymer of the present invention is composed essentially of structural units derived from acrylamide, N,N-dimethylacrylamide, or N-vinyl-2-pyrrolidone and structural units derived from glycidyl acrylate or glycidyl methacrylate, or is composed solely of structural units derived from acrylamide, N,N-dimethylacrylamide, or N-vinyl-2-pyrrolidone and structural units derived from glycidyl acrylate or glycidyl methacrylate. In one embodiment of the present invention, the copolymer of the present invention is composed essentially of structural units derived from N,N-dimethylacrylamide or N-vinyl-2-pyrrolidone and structural units derived from glycidyl methacrylate, or is composed solely of structural units derived from N,N-dimethylacrylamide or N-vinyl-2-pyrrolidone and structural units derived from glycidyl methacrylate. The copolymer according to the present invention is substantially composed of structural units derived from N,N-dimethylacrylamide and structural units derived from glycidyl methacrylate, or is composed only of structural units derived from N,N-dimethylacrylamide and structural units derived from glycidyl methacrylate.

[0054] The weight average molecular weight of the copolymer 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 100,000 to 5,000,000 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.

[0055] The thickness (dry film thickness) of the lubricating layer is, for example, 0.1 to 10 μm, preferably 0.5 to 5 μm, and more preferably about 1 to 3 μm.

[0056] The method for producing the copolymer according to the present invention is not particularly limited, and known methods can be used 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. Among 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 used 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 constitutional units derived from the hydrophilic monomer and constitutional units derived from the hydrophobic monomer.

[0057] In the polymerization, 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. In the polymerization, 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.

[0058] 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 needed. After polymerization, the copolymer is preferably purified by a common purification method such as reprecipitation, dialysis, ultrafiltration, or extraction.

[0059] (Other Components) The lubricating layer essentially contains the copolymer. In addition to the copolymer, the lubricating layer may contain other components. 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 copolymer). 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 copolymer).

[0060] <Method for manufacturing medical device> The medical device according to the present invention is characterized in that the swelling ratio of the lubricating layer is more than 210% and less than 1350%, and the arithmetic mean roughness (Sa) of the lubricating layer surface is less than 1.6 nm. Such a medical device can be manufactured by forming a coating film (precursor layer) containing a copolymer on a substrate layer, and then irradiating this coating film (precursor layer) with an electron beam under specific conditions to form a lubricating layer on the substrate layer.

[0061] That is, another aspect of the present invention provides a method for producing a medical device, comprising: applying a coating liquid containing a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, 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 ((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 1000 kGy to form a lubricating layer having a swelling ratio of more than 210% and less than 1350% ((II-1) electron beam irradiation step).

[0062] In yet another aspect, the present invention provides a method for producing a medical device, the method comprising: applying a coating liquid containing a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, 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 ((I) precursor layer forming step); and irradiating the precursor layer with an electron beam under irradiation conditions defined by the following formula (1) to form a lubricating layer ((II-2) electron beam irradiation step): 0.6<a×b≦27.0 Formula (1) In the above formula (1), a is the electron beam irradiation dose (kGy). Here, a is less than 1000 kGy (a<1000 kGy). Furthermore, b is the composition (mol / mol) of the structural units derived from the hydrophobic monomer having an epoxy group relative to all structural units constituting the copolymer.

[0063] A preferred embodiment of each step will be described below.

[0064] (I) Precursor Layer Formation Step In this step, a solution containing a copolymer, 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 copolymer 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.

[0065] First, a solution (coating liquid) containing the copolymer, 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 copolymer (and other components, if used). From the viewpoint of high solubility, water, acetone, 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.

[0066] The concentration of the copolymer in the coating solution is not particularly limited. For example, the concentration of the copolymer in the coating solution is preferably 0.05% by mass or more and 20% by mass or less, more preferably 1% by mass or more and 15% by mass or less, and particularly preferably 5% by mass or more and 10% by mass or less. If the concentration of the copolymer is within the above range, the resulting lubricating layer can fully exhibit the effects of the present invention. In addition, a lubricating layer of the desired thickness can be easily obtained with a single coating, and the viscosity of the solution is 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.

[0067] Next, the coating liquid prepared as above is applied onto the substrate layer. Here, the substrate layer is the same as that described above, and therefore, a description thereof will be omitted here.

[0068] The method for applying (coating) the copolymer solution (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.

[0069] 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.

[0070] 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.

[0071] 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, in the case of heat treatment, the conditions for the heat treatment are not particularly limited as long as they allow the solvent to be removed (the precursor layer can 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 a precursor layer can be formed on the substrate layer. Furthermore, under the above conditions, aggregation of the epoxy groups of the hydrophobic monomer can be suppressed or prevented.

[0072] 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.

[0073] (II) 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, in either the "(II-1) Electron Beam Irradiation Step" or the "(II-2) Electron Beam Irradiation Step" described below, the precursor layer formed in (I) above is irradiated with an electron beam under specific conditions to form a lubricating layer.

[0074] In step (II-1), the precursor layer formed in step (I) is irradiated with an electron beam at a dose of more than 0 kGy and less than 1000 kGy to form a lubricating layer having a swelling ratio of more than 210% and less than 1350%. Here, the swelling ratio of the lubricating layer refers to the swelling ratio when the lubricating layer is immersed in RO water for 1 minute, and is a value measured according to the method described in "Measurement of Swelling Ratio" in the Examples below.

[0075] In step (II-2), the precursor layer formed in step (I) is irradiated with an electron beam under irradiation conditions defined by the following formula (1) to form a lubricating layer: 0.6<a×b≦27.0 Formula (1) In formula (1), a is the electron beam irradiation dose (kGy). Here, a is less than 1000 kGy (a<1000 kGy). Furthermore, b is the composition (mol / mol) of the structural units derived from the hydrophobic monomer having an epoxy group relative to all structural units constituting the copolymer.

[0076] In the examples of JP-A-8-33704 (corresponding to U.S. Pat. No. 5,670,558), a lubricating layer containing a block copolymer of structural units derived from dimethylacrylamide (a hydrophilic monomer according to the present invention) and structural units derived from glycidyl methacrylate (a hydrophobic monomer having an epoxy group according to the present invention) is formed on a polyurethane sheet by heating at 60°C for 18 hours (thermal curing treatment). In such cases, during the heating process, the epoxy groups of the block copolymers in the coating film (precursor layer according to the present invention) interact with the carbonyl groups of adjacent glycidyl methacrylates, forming crosslinks with other block copolymers and forming a lubricating layer. As this interaction progresses during the heating process, the glycidyl methacrylate-derived structural units (hydrophobic units) of the block copolymers gradually aggregate and aggregate in an attempt to form a stable structure. Therefore, the lubricating layer containing the block copolymer forms a sea-island structure with regions formed by aggregation of hydrophobic units (regions forming convex portions) and regions containing other dimethylacrylamide-derived structural units (hydrophilic units) (regions forming concave portions). The greater the thermal energy during heating, the more the hydrophobic units aggregate (promoting the cross-linking reaction), improving the durability of the lubricating layer. Therefore, a lubricating layer containing the block copolymer requires a heating temperature and heating time above a certain level to achieve durability sufficient for practical use. Therefore, the surface of the lubricating layer formed to improve durability develops large irregularities (high surface roughness). The convex portions of the lubricating layer are prone to peeling off from the surface lubricating layer when the medical device repeatedly slides under harsh conditions (e.g., when the medical device repeatedly slides to deliver the medical device to the lesion site through areas of a biological lumen with a small bending radius, areas with continuous bending portions, or areas with a narrow inner diameter). This reduces the lubricity (slidability).

[0077] In contrast, in the present invention, a lubricating layer is formed by irradiating the precursor layer with an electron beam in the "(II) electron beam irradiation step." When forming a lubricating layer by electron beam irradiation in this step, the energy of the electron beam breaks the molecular bonds of the hydrophobic moieties (especially epoxy groups) in the copolymer, generating multiple radicals (crosslinking points). The generated radicals react with radicals generated in the hydrophobic moieties of the same copolymer or adjacent copolymers, causing crosslinking between the copolymer molecular chains at multiple locations to form a lubricating layer. The time required for electron beam irradiation is very short (less than 1 minute). Therefore, when forming a lubricating layer by electron beam irradiation in this step, the crosslinking reaction proceeds in a state where the copolymer molecular chains are randomly entangled in the precursor layer before the hydrophobic moieties of the copolymer aggregate in the precursor layer. Therefore, the lubricating layer formed by electron beam irradiation in the present invention can reduce the unevenness of the lubricating layer surface (reducing the surface roughness of the lubricating layer surface). Specifically, the surface roughness (arithmetic mean roughness (Sa)) formed on the surface of the lubricating layer is very small (Sa<1.6 nm), and the maximum peak height (Sp) of the surface of the lubricating layer is also small (Sp≦7.2 nm). Furthermore, when the copolymer is a block copolymer having a structural unit derived from a hydrophilic monomer and a structural unit derived from a hydrophobic monomer having an epoxy group, the block copolymer has large blocks (hydrophobic units) formed by the structural units derived from the hydrophobic monomer in its molecular chain. Therefore, when the block copolymer aggregates in the precursor layer, the unevenness of the surface of the lubricating layer is likely to increase. Therefore, when the precursor layer contains a block copolymer having a structural unit derived from a hydrophilic monomer and a structural unit derived from a hydrophobic monomer having an epoxy group, it is particularly preferable to form the lubricating layer by electron beam irradiation in this process. A medical device provided with the lubricating layer of the present invention has a small surface roughness on the surface of the lubricating layer, and therefore, even when the medical device is repeatedly slid under harsh 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 bending sections, or a portion of a biological lumen with a narrow inner diameter), peeling of the lubricating layer caused by the region where the convex portions of the lubricating layer are formed can be effectively suppressed, and the medical device can exhibit excellent lubricity and lubrication maintenance (sliding durability).The above mechanism is speculation and does not limit the technical scope of the present invention.

[0078] When the copolymer is a block copolymer having a structural unit derived from a hydrophilic monomer and a structural unit derived from a hydrophobic monomer having an epoxy group, the region forming the convex portion on the surface of the lubricating layer is a region formed mainly by the aggregation (aggregation) of the structural unit derived from the hydrophobic monomer.Furthermore, the region forming the concave portion on the surface of the lubricating layer is a region mainly containing the structural unit derived from the hydrophilic monomer.In one embodiment of the present invention, the copolymer is a block copolymer having a block formed from a hydrophilic monomer and a block formed from a hydrophobic monomer having an epoxy group, and the region forming the convex portion on the surface of the lubricating layer contains more structural units derived from the hydrophobic monomer than the region forming the concave portion on the surface of the lubricating layer, and the region forming the concave portion contains more structural units derived from the hydrophilic monomer than the region forming the convex portion.

[0079] Here, the "regions where convex portions are formed on the surface of the lubricating layer" are extracted by the following method. First, in the "Evaluation of the regions where convex portions are formed and the regions where concave portions are formed" of the examples below, a frequency distribution table is created for the height of each measurement point in the observation range (0.3 μm long x 0.3 μm wide) of a topographic image (AFM topographic image) of the surface of the lubricating layer obtained using a scanning probe microscope. Next, measurement points corresponding to a range where the cumulative frequency distribution is 70% or more are extracted from the frequency distribution table. The "regions where convex portions are formed on the surface of the lubricating layer" are measurement points corresponding to a range where the cumulative frequency distribution is 70% or more in the frequency distribution table. Furthermore, the "regions where concave portions are formed on the surface of the lubricating layer" are extracted by the following method. First, in the "Evaluation of the regions where convex portions are formed and the regions where concave portions are formed" of the examples below, a frequency distribution table is created for the height of each measurement point in the observation range (0.3 μm long x 0.3 μm wide) of a topographic image (AFM topographic image) of the surface of the lubricating layer obtained using a scanning probe microscope. Next, in the frequency distribution table, measurement points corresponding to a range of 30% or less of the cumulative frequency distribution are extracted. The "area forming a recess on the surface of the lubricating layer" is a measurement point corresponding to a range of 30% or less of the cumulative frequency distribution in the frequency distribution table. The height of the measurement points in the observation area is expressed as the distance (nm) from the bottom surface where the lowest measurement point is located to each measurement point, with the position of the lowest measurement point (recess) from the reference surface (average surface) of the observation area being set to 0.

[0080] In the following Examples, in the "Evaluation of the Regions Forming the Convex Portions and the Regions Forming the Concave Portions" section, the presence of "structural units derived from hydrophobic monomers" can be confirmed by the dark areas observed in the phase image (AFM phase image) of the surface of the lubricating layer obtained using a scanning probe microscope. Furthermore, the presence of "structural units derived from hydrophilic monomers" can be confirmed by the bright areas observed in the phase image (AFM phase image) of the surface of the lubricating layer obtained using a scanning probe microscope.

[0081] Electron beam irradiation is performed at room temperature and does not require heating. This makes it suitable for use on substrates with low heat resistance. Furthermore, since no initiator is required, this method is also highly advantageous in terms of the biological safety required for medical devices.

[0082] In step (II-1), the dose of the electron beam irradiated onto the precursor layer is greater than 0 kGy and less than 1000 kGy. When the dose of the electron beam irradiated onto the precursor layer is 1000 kGy or more, the molecular bonds of the structural units (hydrophilic moieties) derived from the hydrophilic monomer in the copolymer are also cleaved by the energy of the electron beam during electron beam irradiation, forming radicals (crosslinking points). Therefore, during electron beam irradiation, crosslinking reactions between the hydrophilic moieties of the copolymer also proceed, and the crosslinking reaction in the lubricating layer proceeds excessively. Therefore, the lubricating layer cannot achieve a swelling ratio of more than 210%, and its lubricity is also reduced. The dose of the electron beam irradiated onto the precursor layer is preferably small in order to reduce the cleavage of molecular bonds in the hydrophilic moieties of the copolymer during electron beam irradiation and selectively cleave the molecular bonds of the hydrophobic moieties (particularly epoxy groups) of the copolymer. Specifically, the dose of electron beam irradiated to precursor layer is preferably less than 500 kGy, more preferably 300 kGy or less, even more preferably 250 kGy or less, particularly preferably 100 kGy or less.In addition, the dose of electron beam irradiated to precursor layer is more than 0 kGy, preferably 10 kGy or more, more preferably 20 kGy or more, in order to break the molecular bond of the hydrophobic part (particularly, epoxy group) of copolymer during electron beam irradiation to form a plurality of radicals (crosslinking points) (to increase the film strength of lubricating layer).Therefore, the dose of electron beam irradiated to precursor layer is preferably less than 500 kGy, more preferably 10 kGy or more to 300 kGy or less, even more preferably 20 kGy or more to 250 kGy or less, particularly preferably 20 kGy or more to 100 kGy or less. If this irradiation amount, when electron beam is irradiated, the molecular bond of the hydrophobic part (particularly epoxy group) of copolymer can be effectively cut off, and form radical (crosslinking point), so that the lubricating layer does not reduce the lubricity that is based on the hydrophilic part of copolymer, and can increase the film strength by the hydrophobic part of copolymer.Therefore, the lubricating layer can be controlled to the preferred swelling ratio as mentioned above, and can exhibit excellent lubricity and durability.

[0083] In step (II-2), the irradiation conditions for the electron beam irradiated onto the precursor layer satisfy the following formula (1). Formula (1): 0.6<a×b≦27.0 In the above formula (1), a is the electron beam irradiation dose (kGy). In this case, a is less than 1000 kGy (a<1000 kGy). A preferred electron beam irradiation dose (kGy) is the same as the irradiation dose in step (II-1) above. Furthermore, in the above formula (1), b is the composition (mol / mol) of structural units derived from hydrophobic monomers having epoxy groups relative to all structural units constituting the copolymer. The composition (content) of structural units derived from hydrophobic monomers is preferably more than 0 mol% and 20 mol% or less, more preferably 1 mol% or more and 10 mol% or less, relative to all structural units constituting the copolymer. When the content (composition) of structural units derived from hydrophobic monomers is within the above range, the lubricating layer can exhibit good lubricity while also exhibiting sufficient durability.

[0084] The "a × b" value calculated according to the above formula (1) is greater than 0.6 and less than 27.0. When the "a × b" value is 0.6 or less, the crosslinking reaction of the copolymer does not proceed sufficiently when irradiated with an electron beam, and the film strength of the lubricating layer cannot be increased. Therefore, the lubricating layer of the medical device has poor sliding durability. Furthermore, when the "a × b" value exceeds 27.0, the crosslinking reaction between hydrophilic moieties of the copolymer also proceeds when irradiated with an electron beam, and the crosslinking reaction in the lubricating layer proceeds excessively. Therefore, the lubricating layer cannot achieve a swelling ratio exceeding 210%, and its lubricity is also reduced. From the viewpoint of the balance between the lubricity and durability of the lubricating layer, the "a × b" value is preferably 1.0 or more and 25.0 or less, more preferably 1.2 or more and 10.0 or less, and particularly preferably 1.3 or more and less than 5.0.

[0085] In steps (II-1) and (II-2), the irradiation conditions are appropriately selected depending on the reactivity between the desired copolymers or with the material forming the base layer (hence, the durability of the lubricating 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.

[0086] By the above method, a medical device having a lubricating layer with excellent lubricity and durability can be produced.

[0087] [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:

[0088] (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.

[0089] 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.

[0090] The gel fraction of the homopolymer of the hydrophilic monomer was measured at irradiation doses of 250 kGy and 500 kGy according to the following method.

[0091] [Measurement of gel fraction] (Preparation of cured film) A homopolymer of a hydrophilic monomer was dissolved in acetone to a concentration of 8% by mass, and about 5 ml of the solution was uniformly spread on a tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer (PFA) petri dish with a diameter of 75 mm. Subsequently, the petri dish was left standing in a draft chamber for 3 hours to evaporate the acetone, and then a cast film was formed on the petri dish. The cast film was removed from the petri dish, and both sides were irradiated with an electron beam under conditions of an acceleration voltage of 70 kV and an irradiation dose of 250 kGy and 500 kGy to obtain a cured film.

[0092] (Measurement of Gel Fraction) The cured film obtained above was cut into 3 to 5 mm squares to prepare samples.

[0093] 50 mg of this sample was placed in a 50 ml sample tube, followed by the addition of 10 g of N,N-dimethylformamide (DMF). The sample tube was then heated on a hot plate at 100 °C for 1 hour. The heated contents were passed through a pleated metal mesh (#150, diameter 100 mm) to separate the solid component from the DMF solution. The mesh with the attached solid component was immersed in approximately 50 ml of acetone solution for 10 minutes, and the solvent was replaced from DMF to acetone. The mesh was then dried under reduced pressure at 130 °C for 3 hours. After drying, the sample was weighed together with the metal mesh, and the difference between this and the mass of the metal mesh alone, which had been measured previously, was taken as the dried weight (mg) of the sample. The gel fraction (%) was calculated by dividing the dried weight (mg) of the sample by the initial mass (50 mg) [= (dried weight (mg) of the sample (mg) × 100) / initial weight (50 mg)].

[0094] Gel fraction (%) indicates the ease of hardening of the homopolymer of hydrophilic monomer when irradiated with electron beam (the ease of crosslinking reaction between hydrophilic monomers).Therefore, when the gel fraction (%) of the homopolymer of hydrophilic monomer is low (particularly, when the gel fraction is less than 25%), it is considered that when irradiated with electron beam, the crosslinking reaction based on the hydrophilic monomer-derived structural unit of the copolymer that has the structural unit derived from hydrophilic monomer and the structural unit derived from hydrophobic monomer with epoxy group can be suppressed, and the lubricity of the lubricating layer can be maintained.On the other hand, when the gel fraction (%) of the homopolymer of hydrophilic monomer is high (particularly, when the gel fraction is more than 50%), when irradiated with electron beam, the crosslinking reaction based on the hydrophilic monomer-derived structural unit of the copolymer that has the structural unit derived from hydrophilic monomer and the structural unit derived from hydrophobic monomer with epoxy group accelerates, and the lubricity of the lubricating layer is reduced.

[0095] The gel fraction (%) of a hydrophilic monomer homopolymer at 250 kGy indicates the ease of curing of the hydrophilic monomer homopolymer (the ease of crosslinking between hydrophilic monomers) when the hydrophilic monomer homopolymer is irradiated with an electron beam at an irradiation dose of 250 kGy. Therefore, when the gel fraction (%) of the hydrophilic monomer homopolymer at 250 kGy is low (particularly, the gel fraction is less than 25%), it is thought that the occurrence of a crosslinking reaction based on the hydrophilic monomer-derived structural unit can be suppressed even when a copolymer having a hydrophilic monomer-derived structural unit and an epoxy group-containing hydrophobic monomer-derived structural unit is irradiated with an electron beam at an irradiation dose of 250 kGy.

[0096] Similarly, the gel fraction (%) of a homopolymer of a hydrophilic monomer at 500 kGy indicates the ease of curing of the homopolymer of the hydrophilic monomer (the ease of crosslinking between hydrophilic monomers) when the homopolymer of the hydrophilic monomer is irradiated with an electron beam at an irradiation dose of 500 kGy. Therefore, when the gel fraction (%) of the homopolymer of the hydrophilic monomer at 500 kGy is low (particularly, the gel fraction is less than 25%), it is thought that the occurrence of a crosslinking reaction based on the structural units derived from the hydrophilic monomer can be suppressed even when a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group is irradiated with an electron beam at an irradiation dose of 500 kGy.

[0097] Synthesis Example 1: Synthesis of Block Copolymer 1 (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 the mixture was then heated at 50°C for 3 hours. The hydrochloric acid was then removed under reduced pressure to obtain 22.5 g of oligoester. 4.5 g of methyl ethyl ketone was then added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% aqueous hydrogen peroxide, 0.44 g of surfactant dioctyl phosphate, and 120 g of water, and the mixture was allowed to react at -5°C for 20 minutes. The resulting 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 this PPO was polymerized with 9.5 g of glycidyl methacrylate (GMA) as a polymerization initiator and benzene as a solvent for 2 hours at 65°C under reduced pressure while stirring. The reaction product was reprecipitated with diethyl ether to obtain polyGMA having peroxide groups in the molecule (PPO-GMA).

[0098] Subsequently, 1.35 g of the obtained PPO-GMA (corresponding to 9.5 mmol of GMA) was dissolved in chlorobenzene as a polymerization initiator together with 11.2 g (113 mmol) of N,N-dimethylacrylamide (DMAA) as a hydrophilic monomer, and the solution was polymerized by heating to 80°C for 7 hours under a nitrogen atmosphere. The reaction product was recovered by reprecipitation with cyclohexane, and a block copolymer 1 having a DMAA moiety as a hydrophilic moiety and a GMA moiety as a hydrophobic moiety was prepared. The DMAA:GMA ratio of the prepared block copolymer 1 was １ Measurement by H-NMR confirmed that the DMAA:GMA ratio (i.e., the molar ratio of hydrophilic moieties to hydrophobic moieties in block copolymer 1) was 12:1 (molar ratio). Hereinafter, block copolymer 1 will also be referred to as "p(DMAA-GMA)(12 / 1)." The gel fraction of the N,N-dimethylacrylamide (DMAA) homopolymer at 250 kGy was less than 25% by mass. On the other hand, the gel fraction of the N,N-dimethylacrylamide (DMAA) homopolymer at 500 kGy was greater than 50% by mass. Therefore, it is presumed that crosslinking reactions based on structural units derived from N,N-dimethylacrylamide are unlikely to occur when electron beam irradiation is performed at a dose of 250 kGy.

[0099] Synthesis Example 2: Synthesis of Block Copolymer 2 (p(DMAA-GMA) (35 / 1)) Block copolymer 2 having a DMAA moiety as the hydrophilic moiety and a GMA moiety as the hydrophobic moiety was prepared in the same manner as in Synthesis Example 1, except that in Synthesis Example 1, PPO-GMA and N,N-dimethylacrylamide (DMAA) were dissolved in chlorobenzene so that the DMAA:GMA ratio was 35:1 (molar ratio). The DMAA:GMA ratio of the resulting block copolymer 2 was １ H-NMR analysis confirmed that the molar ratio of DMAA to GMA was 35:1. Hereinafter, block copolymer 2 will also be referred to as "p(DMAA-GMA)(35 / 1)."

[0100] Synthesis Example 3: Synthesis of block copolymer 3 (p(VP-GMA)(12 / 1)) Poly-GMA (PPO-GMA) was obtained in the same manner as in Synthesis Example 1.

[0101] Subsequently, 1.077 g of the obtained PPO-GMA (corresponding to 7.5 mmol of GMA), 0.081 g (0.49 mmol) of 2,2'-azobisbutyronitrile (AIBN) as a polymerization initiator, and 10.10 g (corresponding to 90.9 mmol) of 1-vinyl-2-pyrrolidone (VP) as a hydrophilic monomer were dissolved in tetrahydrofuran (THF) and polymerized by heating to 60°C for 5 hours under a nitrogen atmosphere. The reactant was reprecipitated with hexane and recovered to prepare block copolymer 3 having VP moieties as hydrophilic moieties and GMA moieties as hydrophobic moieties. The VP:GMA ratio of the prepared block copolymer 3 was １ H-NMR analysis confirmed that the VP:GMA ratio was 12:1 (molar ratio). Hereinafter, block copolymer 3 will also be referred to as "p(VP-GMA)(12 / 1)." The gel fraction of the 1-vinyl-2-pyrrolidone (VP) homopolymer at 250 kGy was less than 25% by mass. On the other hand, the gel fraction of the 1-vinyl-2-pyrrolidone (VP) homopolymer at 500 kGy was greater than 50% by mass. Therefore, it is presumed that crosslinking reactions based on structural units derived from 1-vinyl-2-pyrrolidone are unlikely to occur when electron beam irradiation is performed at a dose of 250 kGy.

[0102] Example 1 Coating liquid 1 was prepared by dissolving the block copolymer 1 (p(DMAA-GMA)(12 / 1)) obtained in Synthesis Example 1 in acetone to a concentration of 9% by mass.

[0103] Next, a 1.25 mm outer diameter tube substrate made of polyamide elastomer (Grilflex® ELG6260, manufactured by EMS) (nylon elastomer) was dip-coated with the above-prepared Coating Solution 1 at a speed of 5 mm / sec. After air drying, the 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 20 kGy in a nitrogen gas atmosphere, thereby obtaining Sample 1. In the obtained Sample 1, a lubricating layer (dry film thickness: approximately 1 μm) containing block copolymer 1 (p(DMAA-GMA)(12 / 1)) was formed on the tube substrate.

[0104] Example 2 Sample 2 was obtained in the same manner as in Example 1, except that the dose of electron beam irradiation was changed to 50 kGy.

[0105] Example 3 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.

[0106] Example 4 Sample 4 was obtained in the same manner as in Example 1, except that the dose of electron beam irradiation was changed to 300 kGy.

[0107] Example 5 Coating liquid 2 was prepared by dissolving block copolymer 2 (p(DMAA-GMA)(35 / 1)) obtained in Synthesis Example 2 in acetone to a concentration of 7% by mass.

[0108] Sample 5 was obtained in the same manner as in Example 2, except that Coating Liquid 2 prepared above was used instead of Coating Liquid 1 in Example 2.

[0109] Example 6 Sample 6 was obtained in the same manner as in Example 5, except that the dose of electron beam irradiation was changed to 100 kGy.

[0110] Example 7 Sample 7 was obtained in the same manner as in Example 5, except that the dose of electron beam irradiation was changed to 300 kGy.

[0111] Example 8 Sample 8 was obtained in the same manner as in Example 2, except that a tube substrate made of low-density polyethylene (Modic (trademark) M512, manufactured by Mitsubishi Chemical Corporation) with an outer diameter of 0.86 mm was used instead of the polyamide elastomer tube substrate in Example 2.

[0112] Example 9 Sample 9 was obtained in the same manner as in Example 8, except that the dose of electron beam irradiation was changed to 100 kGy.

[0113] Example 10 Sample 10 was obtained in the same manner as in Example 2, except that a φ1.0 mm wire made of stainless steel (SUS304, manufactured by Misumi Corporation) was used instead of the polyamide elastomer tube substrate.

[0114] Example 11 Sample 11 was obtained in the same manner as in Example 10, except that the dose of electron beam irradiation was changed to 100 kGy.

[0115] Example 12 Sample 12 was obtained in the same manner as in Example 10, except that the dose of electron beam irradiation was changed to 300 kGy.

[0116] Example 13 Coating liquid 3 was prepared by dissolving block copolymer 3 (p(VP-GMA)(12 / 1)) obtained in Synthesis Example 3 in acetone / ethanol (weight ratio 1 / 1) to a concentration of 9 mass %.

[0117] Sample 13 was obtained in the same manner as in Example 12, except that Coating Liquid 3 prepared above was used instead of Coating Liquid 1 in Example 12.

[0118] Comparative Example 1 Sample 14 was obtained in the same manner as in Example 1, except that the electron beam irradiation was not performed after natural drying.

[0119] Comparative Example 2 Sample 15 was obtained in the same manner as in Example 1, except that the dose of electron beam irradiation was changed to 1000 kGy.

[0120] Comparative Example 3 Sample 16 was obtained in the same manner as in Example 5, except that the dose of electron beam irradiation was changed to 1000 kGy.

[0121] Comparative Example 4 Sample 17 was obtained in the same manner as in Example 8, except that the dose of electron beam irradiation was changed to 1000 kGy.

[0122] Comparative Example 5 Sample 18 was obtained in the same manner as in Example 1, except that after natural drying, the coated surface was heat-treated at 130°C for 1 minute instead of being irradiated with an electron beam.

[0123] Comparative Example 6 Sample 19 was obtained in the same manner as in Example 1, except that, instead of irradiating the coated surface with an electron beam after natural drying, the coated surface was heat-treated at 130°C for 2 hours.

[0124] Comparative Example 7 Sample 20 was obtained in the same manner as in Example 1, except that, instead of irradiating the coated surface with electron beams after natural drying, the coated surface was heat-treated at 130°C for 10 hours.

[0125] Comparative Example 8 Sample 21 was obtained in the same manner as in Example 5, except that, instead of irradiating the coated surface with electron beams after natural drying, the coated surface was heat-treated at 130°C for 2 hours.

[0126] Comparative Example 9 Sample 22 was obtained in the same manner as in Example 5, except that the dose of electron beam irradiation was changed to 20 kGy.

[0127] Comparative Example 10 Sample 23 was obtained in the same manner as in Example 2, except that poly(N,N-dimethylacrylamide) (polyDMAA) (manufactured by Scientific Polymer, weight average molecular weight (Mw) = 100,000) was used instead of block copolymer 1 (p(DMAA-GMA) (12 / 1)). The gel fraction of the N,N-dimethylacrylamide (DMAA) homopolymer at 250 kGy was less than 25% by mass. On the other hand, the gel fraction of the N,N-dimethylacrylamide (DMAA) homopolymer at 500 kGy was more than 50% by mass.

[0128] Comparative Example 11 Sample 24 was obtained in the same manner as in Comparative Example 10, except that the dose of electron beam irradiation was changed to 100 kGy.

[0129] Comparative Example 12 Polyvinylpyrrolidone (PVP) (manufactured by Tokyo Chemical Industry Co., Ltd., Polyvinylpyrrolidone K90, weight average molecular weight (Mw) = 360,000) was dissolved in ethanol to a concentration of 9% by mass to prepare coating solution 4. The gel fraction of the 1-vinyl-2-pyrrolidone (VP) homopolymer at 250 kGy was less than 25% by mass. On the other hand, the gel fraction of the 1-vinyl-2-pyrrolidone (VP) homopolymer at 500 kGy was more than 50% by mass.

[0130] Sample 25 was obtained in the same manner as in Example 11, except that Coating Liquid 4 prepared above was used instead of Coating Liquid 1 in Example 11.

[0131] Comparative Example 13 Sample 26 was obtained in the same manner as in Comparative Example 12, except that the dose of electron beam irradiation was changed to 300 kGy.

[0132] Comparative Example 14 Sample 27 was obtained in the same manner as in Example 13, except that instead of irradiating the coated surface with an electron beam after natural drying, the coated surface was heat-treated at 130°C for 3 hours.

[0133] The substrate materials, (co)polymers of the lubricating layers, and conditions for forming the lubricating layers (electron beam irradiation conditions, heating conditions) for Samples 1 to 27 obtained above are summarized in Table 3 below. In Tables 2 to 4 below, "irradiation conditions (kV-kGy)" indicates the acceleration voltage (kV) and dose (kGy) during electron beam irradiation. For example, the electron beam irradiation conditions in Example 1 indicate an acceleration voltage of 60 kV and a dose of 20 kGy. Furthermore, "heating conditions" indicate the heating temperature (°C) and heating time (minutes or hours) during heat treatment. For example, the heating conditions in Comparative Example 5 indicate a heating temperature of 130°C and a heating time of 1 minute. Furthermore, "irradiation dose × GMA composition" represents the product of the electron beam irradiation dose (kGy) and the composition (mol / mol) of structural units derived from GMA (a hydrophobic monomer having an epoxy group) relative to all structural units constituting each copolymer [= (electron beam irradiation dose (kGy)) × (composition (mol / mol) of structural units derived from GMA (a hydrophobic monomer having an epoxy group) relative to all structural units constituting each copolymer)] (i.e., the "a × b" value in the above formula (1)).

[0134] For the samples 1 to 13 obtained above, the regions where the convex portions are to be formed and the regions where the concave portions are to be formed were evaluated according to the following method.

[0135] [Evaluation of Regions Forming Convexities and Regions Forming Concave Portions] In the profile image (AFM profile image), the unevenness of the lubricating layer surface (regions forming convexities and regions forming concave portions) can be observed within an observation range (0.3 μm vertical x 0.3 μm horizontal). The unevenness of the lubricating layer surface is thought to be formed by phase separation between structural units derived from hydrophilic monomers (e.g., dimethylacrylamide, 1-vinyl-2-pyrrolidone) and structural units derived from hydrophobic monomers (GMA). Compared to electron beam curing conditions (when the coated surface is cured by heat treatment), heat curing conditions more effectively promote the aggregation of structural units derived from hydrophobic monomers on the coated surface. Therefore, compared to electron beam curing conditions, heat curing conditions result in greater unevenness of the lubricating layer surface (greater surface roughness). In this evaluation, the following verification confirmed that the regions forming convexities on the lubricating layer surface are primarily composed of aggregates of structural units derived from hydrophobic monomers.

[0136] A sample cut into a 5 mm length was fixed to a glass plate with adhesive and dried overnight. After drying, the sample was immersed in 50 mL of RO water for 10 minutes, and then the surface of the sample was rinsed with RO water about five times using a pipette. The sample was then left to stand for 24 hours in an environment of 23°C and 45% RH to obtain a sample.

[0137] Next, a scanning probe microscope (AFM5200S, manufactured by Hitachi High-Tech Corporation) was used to obtain a topographical image (AFM topographical image) and a phase image (AFM phase image) of the lubricating layer surface of the sample. The cantilever used was an SI-DF40P2, and the observation area was 0.3 μm square (0.3 μm long × 0.3 μm wide).

[0138] It was confirmed that the contrast of the acquired topographical image (AFM topographical image) was inverted with respect to the contrast of the acquired phase image (AFM phase image).

[0139] The bright areas observed in the topography image (AFM topography image) are higher in the observation range than the dark areas observed in the topography image. Therefore, the regions forming the convex portions on the surface of the lubricating layer (regions where the cumulative frequency distribution is 70% or more in the frequency distribution table when a frequency distribution table for the heights of each measurement point in the observation range of the topography image is created) are located in the bright areas of the topography image. Also, the regions forming the concave portions on the surface of the lubricating layer (regions where the cumulative frequency distribution is 30% or less in the frequency distribution table when a frequency distribution table for the heights of each measurement point in the observation range of the topography image is created) are located in the dark areas of the topography image.

[0140] On the other hand, a bright area observed in a phase image (AFM phase image) means that the phase difference is greater than that of a dark area observed in the phase image. Therefore, when the lubricating layer is composed of a copolymer of a constitutional unit derived from a hydrophilic monomer and a constitutional unit derived from a hydrophobic monomer, it is estimated that in the phase image, the constitutional unit derived from the hydrophilic monomer, which is likely to adsorb moisture in the measurement environment, corresponds to the bright area, and the constitutional unit derived from the hydrophobic monomer corresponds to the dark area.

[0141] From the above, it is considered that the bright areas of the acquired shape image (particularly the areas forming the convex portions on the surface of the lubricating layer) are composed of aggregates of structural units (GMA) derived from the hydrophobic monomer. That is, it is considered that the bright areas of the acquired shape image (the areas forming the convex portions on the surface of the lubricating layer) are areas where more structural units derived from the hydrophobic monomer of the copolymer are present than the dark areas of the shape image (the areas forming the concave portions on the surface of the lubricating layer). On the other hand, it is considered that the dark areas of the acquired shape image (the areas forming the concave portions on the surface of the lubricating layer) are areas where more structural units derived from the hydrophilic monomer of the copolymer are present than the bright areas of the shape image (the areas forming the convex portions on the surface of the lubricating layer).

[0142] For the samples 1 to 13 obtained above, topography images (AFM topography images) and phase images (AFM phase images) were obtained according to the above method. As a result, it was confirmed that the regions forming the convex portions on the surface of the lubricating layer contained more structural units derived from the hydrophobic monomer (GMA) than the regions forming the concave portions on the surface of the lubricating layer, and that the regions forming the concave portions contained more structural units derived from the hydrophilic monomer (DMAA or VP) than the regions forming the convex portions.

[0143] The swelling ratio of the lubricating layer was measured for Samples 1 to 27 obtained above according to the following method, and the results are shown in Tables 2, 3 and 4 below.

[0144] [Measurement of Swelling Ratio] The swelling ratio (expansion ratio) of the lubricating layer was calculated using the following formula.

[0145] 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.

[0146] 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 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.

[0147] In the above formula, the specimen outer diameter was measured using a laser diameter measuring device (LASER SCAN MCROMETER LS, manufactured by KEYENCE). The specimen was immersed in RO water for 1 minute, and the outer diameter of the specimen 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 specimen. When calculating the average, obvious noise not caused by coating, such as foreign matter adhesion, was excluded. Furthermore, if at least a portion of the measurement specimen 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 specimen before immersion in RO water, and "specimen outer diameter (μm) upon swelling" refers to the measured outer diameter of the specimen after immersion in RO water for 1 minute.

[0148] The arithmetic mean roughness (Sa) and maximum peak height (Sp) of the lubricating layer surface were measured for Samples 1 to 27 obtained above according to the following method. The results are shown in Tables 2, 3, and 4 below.

[0149] [Surface Roughness Evaluation] Using a scanning probe microscope (AFM5200S, manufactured by Hitachi High-Tech Corporation) and its software (AFM5000II), the arithmetic mean roughness (Sa) and maximum peak height (Sp) of the lubricating layer surface were measured at a temperature of 22°C and a relative humidity of 40% RH according to the following procedure.

[0150] A sample cut to a length of 5 mm was fixed to a glass plate with adhesive and dried overnight. After drying, the sample was immersed in 50 mL of RO water for 10 minutes, and then the surface of the sample was rinsed with RO water about five times using a pipette. The sample was then left for 24 hours in an environment of 23 ° C and 45% RH to obtain a sample. Next, a scanning probe microscope was used to obtain a topographical image (AFM topographical image) of the lubricating layer surface of this sample. In addition, an SI-DF40P2 cantilever was used, and the observation area was 3 μm square (3 μm vertical x 3 μm horizontal).

[0151] The arithmetic mean roughness (Sa) (calculated mean height) and maximum peak height (Sp) were calculated for the obtained topographical images using analysis software. If necessary, flattening was performed before calculating the Sa value.

[0152] The number of fine particles was measured for the above-obtained samples 1 to 4 and 19 according to the following method. The results are shown in Table 2 below.

[0153] [Evaluation of Particle Count] The number of particle generation from the sample was evaluated using an Oak River sliding tester (DL1000, manufactured by OAKRIVER TECHNOLOGY A PaR Systems Company) and a liquid particle counter (HIAC9703+, manufactured by HIAC) according to the following procedure.

[0154] 160 mL of RO water was placed in the container, and the sample was fixed so that the measurement point was immersed. After immersing the sample for 1 minute, the sample was clamped with a silicone terminal (13 mm x 32 mm) under a load of 500 gf and set. While applying a grip force of 500 gf to the silicone terminal, the same point was slid vertically 20 times under the conditions of a sliding distance of 60 mm and a sliding speed of 20 mm / sec. After sliding, the sample was rotated 90 degrees in the circumferential direction and slid again under the same conditions. The RO water in the container was then recovered, and the number of particles 10 μm or larger in the RO water was measured (particles / mL) using a liquid-borne particle counter.

[0155] Furthermore, the lubricity and lubrication maintenance (durability) of Samples 1 to 27 obtained above were evaluated according to the following methods. The results are shown in Table 3 below.

[0156] [Sensory Evaluation] Each sample was immersed in water so that the lubricating layer (coated surface) was submerged. After 1 minute, while still immersed in water, the lubricating layer was pinched with the pads of the fingers and rubbed 30 times in a width of approximately 5 cm in the longitudinal direction of the sample. The slipperiness was evaluated after the fifth rub ("Slipperiness" in Table 3 below) and the 30th rub ("Durability" in Table 3 below). The rubbing strength and speed were kept as similar as possible between samples. The slipperiness (lubricity) after the fifth rub and the slipperiness (durability) after the 30th rub were evaluated according to the criteria in Table 1 below. Note that, for the evaluation criteria for slipperiness, the resistance value measured by the Oak River sliding tester in the "Sliding Durability Evaluation" section described below is also listed as a guide.

[0157]

[0158] Furthermore, the sliding durability (lubrication maintenance ability) of the above-obtained samples 1 to 9, 15 to 19, and 21 was evaluated according to the following method. The results are shown in Table 4 below.

[0159] [Evaluation of Sliding Durability] The sliding resistance value of the lubricating layer of each sample was measured using an Oakriver sliding tester (DL1000, manufactured by OAKRIVER TECHNOLOGY A PaR Systems Company) according to the following procedure.

[0160] The container was filled with RO water, and each sample was fixed so that the measurement point was immersed in the RO water. After immersing the sample for 1 minute, the sample was clamped with a silicone terminal (13 mm x 32 mm) under a load of 500 gf and set. While applying a grip force of 500 gf to the silicone terminal, the sample was moved vertically at a sliding distance of 60 mm and a sliding speed of 20 mm / sec, repeatedly sliding the same point of the sample 20 times. The sliding resistance values ​​(gf) were measured when the sample was pulled up vertically for the 5th, 10th, and 20th times. When the sample was a tube substrate, a core was inserted into the inner cavity of the sample (tube substrate) before measuring the sliding resistance value.

[0161]

[0162]

[0163]

[0164]

[0165]

[0166] The results in Tables 2 to 4 show that Samples 1 to 13 of the examples are able to achieve both lubricity (slidability) and durability compared to Samples 14 to 27 of the comparative examples.

[0167] As is clear from Table 3, samples 23 to 26 of Comparative Examples 10 to 13, which do not have a structural unit derived from a hydrophobic monomer (GMA), partially dissolved during swelling ratio measurement, making it impossible to measure the swelling ratio, compared to samples 2 to 3 and 11 to 12 of Examples 2 to 3 and 11 to 12. This is presumably because homopolymers of hydrophilic monomers (DMAA, VP) undergo little or no crosslinking reaction between homopolymers upon electron beam irradiation, even under the same electron beam irradiation conditions as samples 2 to 3 and 11 to 12 of Examples 2 to 3 and 11 to 12. For this reason, in order to improve the durability of the lubricating layer while maintaining the lubricity of the lubricating layer, it is considered necessary for the copolymer to have a structural unit derived from a hydrophobic monomer (GMA).

[0168] Example 1 and Comparative Examples 5 to 7 are similar except for the different formation methods: electron beam irradiation (Example) and heat treatment (Comparative Examples). As is clear from Tables 3 and 4, Sample 1 of Example 1, in which the lubricating layer was formed by electron beam irradiation, can maintain excellent lubricity (low sliding resistance value) (excellent lubricity and durability (sliding durability)). In contrast, Sample 18 of Comparative Example 5, in which the lubricating layer was formed by heat treatment in a short time, had a low initial (fifth) sliding resistance value, but the sliding resistance value increased with each repeated sliding, resulting in poor durability (sliding durability). Sample 19 of Comparative Example 6, in which the lubricating layer was formed by heat treatment for a longer time than Comparative Example 5, had excellent durability (sliding durability), but its sliding resistance value was higher than that of Example 1 and its lubricity was poor. Sample 20 of Comparative Example 7, in which the lubricating layer was formed by heat treatment for a longer time than Comparative Examples 5 and 6, had better durability (sliding durability) than Comparative Example 5, but poorer lubricity. The above results suggest that the lubricating layer according to the present invention can achieve both excellent lubricity and durability. This can also be seen from the results of Examples 5 to 7 and Comparative Example 8.

[0169] As is clear from Tables 3 and 4, Samples 15 to 17 of Comparative Examples 2 to 4 have swelling ratios of 210% or less. These samples have excellent durability but poor lubricity. This is presumably because, due to the high electron beam irradiation dose of 1000 kGy, during electron beam irradiation, not only the molecular bonds of the structural units derived from the hydrophobic monomer (GMA) but also the molecular bonds of the structural units derived from the hydrophilic monomer (DMAA) are broken, forming radicals (crosslinking points), and crosslinking reactions between hydrophobic moieties as well as between hydrophilic moieties proceed, resulting in excessive crosslinking in the lubricating layer.

[0170] Examples 1 to 4 and Examples 5 to 7 are similar except for the electron beam irradiation dose. As is clear from Table 4, from the viewpoint of the sliding resistance value (lubricity) after the fifth cycle, it is found that the electron beam irradiation dose is preferably less than 300 kGy (for example, 250 kGy or less).

[0171] Comparative Examples 5 to 7 were similar except for the heat treatment time. As is clear from Table 3, the surface roughness and maximum peak height increased as the heat treatment time increased. This is presumably due to the fact that the structural units derived from the hydrophobic monomer (GMA) gradually aggregate and form a stable structure during the heat treatment. Furthermore, Sample 21 of Comparative Example 8 did not exhibit sufficient durability of the lubricating layer for practical use, similar to Sample 18 of Comparative Example 5, because the heat treatment time for block copolymer 2 (p(DMAA-GMA)(35 / 1)) was insufficient. This is presumably due to the insufficient heat treatment time, which resulted in the structural units derived from the hydrophobic monomer (GMA) not sufficiently aggregating during the heat treatment. Therefore, Comparative Example 8 had similar surface roughness and maximum peak height to Examples 1 to 13, but exhibited a high swelling ratio and did not exhibit sufficient durability in the sensory evaluation and sliding durability evaluation. As is clear from Tables 3 and 4, Samples 1 to 7 of Examples 1 to 7 have higher lubricating layer durability than Samples 18, 20, and 21 of Comparative Examples 5, 7, and 8. This is thought to be because, as mentioned above, in Comparative Examples 5 and 8, the heat treatment time was insufficient, and the structural units derived from the hydrophobic monomer (GMA) did not sufficiently aggregate during the heat treatment, resulting in low film strength of the lubricating layer. Furthermore, in Comparative Example 7, the heat treatment time was long, and the aggregation of the structural units derived from the hydrophobic monomer (GMA) progressed excessively during the heat treatment, resulting in increased surface roughness and maximum peak height. On the other hand, Sample 19 of Comparative Example 6, like Samples 1 to 7 of Examples 1 to 7, showed good results in terms of slipperiness and durability in the sensory evaluation. However, Samples 1 to 4 of Examples 1 to 4 showed a significantly reduced number of fine particles in the fine particle count evaluation compared to Sample 19 of Comparative Example 6. This is thought to be because Samples 1 to 4 of Examples 1 to 4 have small surface roughness and maximum peak height (small unevenness on the lubricating layer surface), which reduces damage to the lubricating layer surface due to contact with the silicone terminal surface during sliding.

[0172] As described above, Sample 19 of Comparative Example 6 exhibited similar durability to Samples 1 to 4 of Examples 1 to 4 in terms of the lubricity and durability evaluated by sensory evaluation. On the other hand, Sample 19 of Comparative Example 6 had a higher surface roughness and maximum peak height than Samples 1 to 4 of Examples 1 to 4. Furthermore, Samples 1 to 4 of Examples 1 to 4 had a lower number of fine particles than Sample 19 of Comparative Example 6. These results demonstrate that a low surface roughness and maximum peak height of the lubricating layer reduces the number of fine particles generated during sliding of the lubricating layer, thereby improving the durability of the lubricating layer, and that this effect can be achieved by electron beam irradiation. Furthermore, these results demonstrate that the medical device of the present invention is expected to exhibit excellent lubricity and lubrication maintenance (sliding durability) even when sliding is repeated under harsh conditions (e.g., when the medical device is repeatedly slid to deliver the medical device 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, or a portion of a biological lumen with a narrow inner diameter, etc.).

[0173] Examples 12 and 13 are similar except for the hydrophilic monomer constituting the copolymer contained in the lubrication layer. As shown in Table 3, Sample 12 of Example 12, in which the hydrophilic monomer is N,N-dimethylacrylamide, and Sample 13 of Example 13, in which the hydrophilic monomer is 1-vinyl-2-pyrrolidone, exhibit similar results in terms of slipperiness and durability in sensory evaluation. Meanwhile, the surface roughness and maximum peak height of Sample 12 of Example 12 are lower than those of Sample 13 of Example 13. From these results, it is presumed that Sample 12 of Example 12 will exhibit superior slipperiness and durability to Sample 13 of Example 13 if the rubbing conditions are made more severe (e.g., by increasing the number of rubs or increasing the rubbing strength).

[0174] This application is based on Japanese Patent Application No. 2024-52926, filed on March 28, 2024, the disclosure of which is incorporated by reference in its entirety.

Claims

1. A medical device comprising a base layer and a lubricating layer formed on at least a portion of the base layer, wherein the lubricating layer contains a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, the swelling ratio of the lubricating layer is greater than 210% and less than 1350%, and the lubricating layer has an irregular surface, and the arithmetic mean roughness (Sa) of the surface is less than 1.6 nm.

2. The medical device according to claim 1, wherein the hydrophilic monomer is made of a material whose homopolymer has a gel fraction of less than 25% by mass at 250 kGy.

3. The medical device according to claim 1, wherein the hydrophilic monomer-derived structural unit is a structural unit derived from at least one monomer selected from the group consisting of 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.

4. The medical device according to claim 1, wherein the structural unit 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.

5. The medical device according to claim 1, wherein the copolymer contains structural units derived from the hydrophilic monomer in a ratio of 5 to 50 moles per mole of structural units derived from the hydrophobic monomer having an epoxy group.

6. The medical device according to claim 1, wherein the arithmetic mean roughness (Sa) of the surface of the lubricating layer is 0.55 nm or less.

7. The medical device according to claim 1, wherein the maximum peak height (Sp) of the surface of the lubricating layer is 7.2 nm or less.

8. The medical device according to claim 1, wherein the swelling ratio of the lubricating layer is 215% or more and 1150% or less.

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

10. The medical device according to claim 1, wherein the copolymer is a block copolymer having a block formed from a hydrophilic monomer and a block formed from a hydrophobic monomer having an epoxy group, and the regions forming the convex portions on the surface of the lubricating layer contain more structural units derived from the hydrophobic monomer than the regions forming the concave portions on the surface of the lubricating layer, and the regions forming the concave portions contain more structural units derived from the hydrophilic monomer than the regions forming the convex portions.

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

12. A method for manufacturing a medical device, comprising: applying a coating liquid containing a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, 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 1000 kGy to form a lubricating layer having a swelling ratio of more than 210% and less than 1350%.

13. A method for producing a medical device, comprising: applying a coating liquid containing a copolymer having structural units derived from a hydrophilic monomer and structural units derived from a hydrophobic monomer having an epoxy group, 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 under irradiation conditions defined by the following formula (1) to form a lubricating layer: 0.6<a×b≦27.0 Formula (1) In formula (1), a is the electron beam irradiation dose (kGy) and is less than 1000 kGy, and b is the composition (mol / mol) of the structural units derived from the hydrophobic monomer having an epoxy group relative to all structural units constituting the copolymer.

14. The method of claim 12 or 13, wherein the radiation dose is less than 500 kGy.

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