Medical instrument and uneven distribution measurement method

Abstract

Provided is a medical instrument having excellent slidability and durability. This medical instrument comprises a substrate layer and a surface lubricating layer supported on at least a portion of the substrate layer, wherein: the surface lubricating layer contains a block copolymer which has a constitutional unit (A) derived from a reactive monomer having an epoxy group and a constitutional unit (B) derived from a hydrophilic monomer, and a hydrophobic resin; and the standard deviation of the R values of the surface lubricating layer dyed with a Congo red solution is at most 10.

Description

Medical devices and uneven distribution measurement methods

[0001] The present invention relates to a medical device and a method for measuring uneven distribution.

[0002] Medical devices inserted into living bodies, such as catheters, guidewires, and indwelling needles, are required to exhibit excellent lubricity in order to reduce tissue damage to blood vessels and improve operability for surgeons. For this reason, methods of coating the surface of a substrate layer with a hydrophilic polymer having lubricity have been developed and put into practical use. In such medical devices, elution or peeling of the hydrophilic polymer from the surface of the substrate layer poses problems in terms of maintaining operability, etc. 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 No. 8-33704 discloses a medical device in which a surface lubricating layer is formed on the surface of the substrate by dissolving a water-soluble or water-swellable polymer in a solvent that swells the substrate of the medical device to prepare a polymer solution, immersing the substrate of the medical device in this polymer solution to cause it to swell, and then crosslinking or polymerizing the polymer on the surface of the substrate. According to the technology disclosed in Japanese Patent Laid-Open No. 8-33704, a surface lubricating layer that exhibits relatively good lubricity can be fixed to the substrate.

[0004] Japanese Patent Laid-Open Publication No. 8-33704 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 epoxy groups of the block copolymer can be crosslinked by heating, forming a surface lubricating layer that is relatively resistant to peeling. However, there is a trade-off between good lubricity (sliding properties) and excellent durability (especially sliding durability), and a technology that can achieve both is needed.

[0005] In particular, medical devices have become significantly smaller and thinner in recent years, and medical procedures in which medical devices approach lesions through more flexible and narrow biological lumens such as blood vessels are becoming more common. Furthermore, as medical procedures become more complex, the operation of medical devices can take a long time. Therefore, in order to maintain good operability of medical devices even in complex lesions, there is a demand for technology that further enhances the durability (particularly, sliding durability) of the medical device surface (surface lubricating layer) compared to conventional technologies. More specifically, there is a demand for devices with excellent durability (particularly, sliding durability) that can maintain high lubricity (slidability) even when the medical device surface (surface lubricating layer) is repeatedly slid.

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

[0007] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a medical device having a surface lubricating layer that exhibits excellent durability and sliding properties.

[0008] The present inventors have conducted extensive research to solve the above problems, and as a result, have discovered that the above object can be achieved by controlling the thickness variation of a surface lubricating layer containing a predetermined component in a medical device to a certain value or less, thereby completing the present invention.

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

[0010] One aspect of the present invention is: 1. A medical device comprising a base layer and a surface lubricating layer supported on at least a portion of the base layer, wherein the surface lubricating layer comprises a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, and a hydrophobic resin, and the standard deviation of the R value of the surface lubricating layer stained with Congo Red solution is 10 or less.

[0011] 2. In the medical device described in 1 above, it is preferable that the ratio (molar ratio) of the structural unit (A) derived from the reactive monomer having an epoxy group to the structural unit (B) derived from the hydrophilic monomer in the block copolymer is 1:20 to 1:50.

[0012] 3. In the medical device described in 1. or 2. above, it is preferable that the content (mass %) of the hydrophobic resin in the surface lubricating layer is less than the content (mass %) of the block copolymer.

[0013] 4. In the medical device according to any one of the above items 1 to 3, the hydrophobic resin is preferably polyvinyl chloride (PVC) resin.

[0014] 5. In the medical device according to any one of 1. to 4. above, the reactive monomer having an epoxy group preferably includes at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether.

[0015] 6. In the medical device according to any one of 1. to 5. above, the hydrophilic monomer preferably includes at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone.

[0016] 7. In the medical device according to any one of 1. to 6. above, it is preferable that the sliding resistance value of the surface lubricating layer after 10 sliding cycles in a sliding resistance test is 8.5 gf or less.

[0017] One aspect of the present invention is a method for measuring uneven distribution, which evaluates the uneven distribution of a surface lubricating layer in a medical device having a surface lubricating layer by the standard deviation of the R value of the surface lubricating layer stained with Congo red solution.

[0018] Fig. 1 is a partial cross-sectional view schematically showing the layer structure on the surface of a representative embodiment of a medical device (catheter) according to the present invention. Fig. 2 is a partial cross-sectional view schematically showing the layer structure on a surface with uneven thickness as a comparative example to the embodiment of Fig. 1. Fig. 3 is a diagram for explaining a method for calculating the average R value and the standard deviation of the R value. Fig. 4 is a schematic diagram of a sliding property and durability test device (friction measuring device) used in a reference example.

[0019] A medical device according to one embodiment of the present invention is a medical device comprising a base layer and a surface lubricating layer supported on at least a portion of the base layer, wherein the surface lubricating layer comprises a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, and a hydrophobic resin, and the standard deviation of the R value of the surface lubricating layer stained with Congo red solution is 10 or less.

[0020] Hereinafter, embodiments of the present invention will be described. 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. The dimensional proportions in the drawings are exaggerated for the convenience of explanation and may differ from the actual proportions. Furthermore, when describing embodiments of the present invention with reference to the drawings, identical elements will be designated by the same reference numerals, and redundant explanations will be omitted.

[0021] Herein, the structural unit (A) derived from a reactive monomer having an epoxy group is also referred to simply as the "structural unit (A) according to the present invention" or "structural unit (A)." Herein, the structural unit (B) derived from a hydrophilic monomer is also referred to simply as the "structural unit (B) according to the present invention" or "structural unit (B)." Herein, a block copolymer having structural units (A) and (B) is also referred to simply as the "block copolymer according to the present invention" or "block copolymer."

[0022] In this specification, when a structural unit is defined as being "derived from" a specific monomer, it means that the structural unit is a divalent structural unit generated by cleavage of one of the polymerizable unsaturated double bonds of the corresponding monomer.

[0023] As used herein, the term "(meth)acrylic" encompasses both acrylic and methacrylic. Thus, for example, the term "(meth)acrylic acid" encompasses both acrylic acid and methacrylic acid. Similarly, the term "(meth)acryloyl" encompasses both acryloyl and methacryloyl. Thus, for example, the term "(meth)acryloyl group" encompasses both acryloyl and methacryloyl groups. Similarly, the term "(meth)acrylate" encompasses both acrylate and methacrylate. For example, the term "alkoxyalkyl(meth)acrylate" encompasses both alkoxyalkylacrylate and alkoxyalkylmethacrylate.

[0024] Furthermore, throughout this specification, singular expressions should be understood to include the plural concept unless otherwise specified. 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 have the meaning 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 the case of conflict, the present specification (including definitions) shall prevail. The present invention is not limited to the following embodiments and can be modified in various ways within the scope of the claims. Furthermore, in this specification, the term "X to Y" indicating a range includes X and Y and means "at least X and at most Y." Furthermore, "X and / or Y" includes each of X and Y and all combinations of one or more thereof, specifically means at least one of X and Y, and includes X alone, Y alone, and the combination of X and Y. Furthermore, unless otherwise specified, the concentration "%" represents the mass concentration "% by mass."

[0025] 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 50% RH.

[0026] [Medical Device] A preferred embodiment of the medical device according to the present invention will now be described with reference to FIGS.

[0027] Fig. 1 is a partial cross-sectional view schematically showing a laminated structure without thickness unevenness on the surface of a catheter, which is a representative embodiment of a medical device according to the present invention (also abbreviated as "medical device" in this specification). Fig. 2 is a partial cross-sectional view schematically showing a laminated structure with thickness unevenness as a comparative example of this embodiment. Note that the symbols in Figs. 1 and 2 represent the following: symbol 1 represents a base layer; symbol 2 represents a surface lubricating layer; symbol 3 represents a lumen; and symbol 10 represents a catheter.

[0028] 1, the catheter 10 of this embodiment comprises a base layer 1 and a surface lubricating layer 2 containing a block copolymer and a hydrophobic resin, which is provided on at least a portion of the base layer 1 (the figure shows an example in which the surface is provided on the entire surface (entire surface) of the base layer 1 in the drawing). The catheter 10 has a lumen 3 that runs from the distal end to the proximal end.

[0029] (Substrate Layer (Substrate)) The substrate layer used in this embodiment may be made of any material, and the material is not particularly limited. Specifically, examples of materials constituting the substrate layer include polymer materials (resin materials) and polymer materials with metal wires embedded therein.

[0030] Among the materials constituting the base layer, the polymer material (resin material or elastomer material) is not particularly limited, and may be a polymer material commonly used in medical devices such as catheters, introducers, guidewires, indwelling needles, etc. Specific examples include polyamide resins, polyolefin resins such as polyethylene resins and polypropylene resins, modified polyolefin resins, cyclic polyolefin resins, epoxy resins, polyurethane resins, diallyl phthalate resins (allyl resins), polycarbonate resins, fluororesins, amino resins (urea resins, melamine resins, benzoguanamine resins), polyester resins such as polyethylene terephthalate resins and polybutylene terephthalate resins, styrene resins, acrylic resins, polyacetal resins, vinyl acetate resins, phenolic resins, vinyl chloride resins, silicone resins (silicon resins), polyether resins, and polyimide resins.

[0031] Thermoplastic elastomers such as polyurethane elastomers, polyester elastomers, and polyamide elastomers (nylon elastomers) can also be used as materials for the substrate layer.

[0032] These polymer materials may be used alone, as a mixture of two or more types, or as a copolymer of two or more monomers constituting any of the above resins or elastomers. Among these, preferred polymer materials are polyethylene resins, polyurethane resins, polyethylene terephthalate resins, polybutylene terephthalate resins, polyester elastomers, polyamide resins, and polyamide elastomers. Polyamide resins and polyamide elastomers are more preferred, and block copolymers of polybutylene terephthalate and polytetramethylene glycol and block copolymers of nylon 12 and polytetramethylene glycol are particularly preferred. Carboxyl groups and amino groups as terminal groups contained in block copolymers of polybutylene terephthalate and polytetramethylene glycol, polyamide resins, and polyamide elastomers can undergo crosslinking reactions with epoxy groups in the block copolymers. The polymer material may be appropriately selected based on the substrate layer of the intended use, such as a catheter, guidewire, or indwelling needle.

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

[0034] (Surface lubricating layer) The surface lubricating layer 2 is supported on at least a part of the base layer 1. Here, the reason why the surface lubricating layer 2 is supported on at least a part of the surface of the base layer 1 is that in medical devices such as catheters, guide wires, and indwelling needles, which are intended for use, it is not necessary for all surfaces (entire surfaces) of these medical devices to have lubricity (slidability) when wet, and it is sufficient that the surface lubricating layer 2 is supported only on the surface portion that is required to have lubricity (slidability) when wet, for example, the tip portion (sometimes a part or sometimes the entire portion).

[0035] A surface lubricating layer according to one embodiment of the present invention comprises a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, and a hydrophobic resin.

[0036] <Block copolymer> In the present invention, the block copolymer forms a surface lubricating layer supported on at least a portion of the base layer. That is, in the medical device obtained by the method of the present invention, the surface lubricating layer contains a block copolymer.

[0037] The block copolymer according to the present invention has a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer.

[0038] The reactive monomer having epoxy group that constitutes block copolymer has epoxy group as reactive group.By introducing the structural unit (A) derived from this reactive monomer into block copolymer, epoxy group ring-opens, and the cross-linking (bonding) between block copolymers progresses, and the film strength of surface lubrication layer increases.In addition, when base layer is made of resin material, the cross-linking (bonding) between block copolymer and base layer also occurs due to the open epoxy group.

[0039] The reactive monomer constituting the block copolymer is not particularly limited as long as it has an epoxy group, and known compounds can be used. Among them, the reactive 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 methacrylate, and allyl glycidyl ether, because this makes it easier to control the crosslinking or polymerization of the block copolymer. Among them, glycidyl (meth)acrylate is more preferred, and glycidyl methacrylate is particularly preferred, in consideration of the ability to further promote the crosslinking reaction and ease of production.

[0040] The reactive monomers may be used alone or in combination of two or more. That is, the reactive site derived from the reactive monomer may be a homopolymer type composed of one type of reactive monomer alone, or a copolymer type composed of two or more types of the reactive monomers. When two or more types are used, the reactive site may be in the form of a block copolymer or a random copolymer.

[0041] That is, in a preferred embodiment of the present invention, the reactive monomer having an epoxy group includes at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether. In a more preferred embodiment of the present invention, the reactive monomer having an epoxy group is at least one of glycidyl acrylate and glycidyl methacrylate. In a particularly preferred embodiment of the present invention, the reactive monomer having an epoxy group is glycidyl methacrylate. In a preferred embodiment of the present invention, the reactive monomer having an epoxy group is a (meth)acrylate having an epoxy alkyl group. The alkyl group preferably has 1 to 3 carbon atoms. In a preferred embodiment of the present invention, the reactive monomer having an epoxy group is a (meth)acrylate having an epoxy group.

[0042] The hydrophilic monomers constituting the block copolymer swell when in contact with aqueous solvents such as body fluids, thereby imparting lubricity (slidability) to the medical device. Therefore, by introducing the structural unit (B) derived from such a hydrophilic monomer into the block copolymer, the lubricity (slidability) of the medical device can be improved, thereby reducing friction when the medical device comes into contact with a lumen wall such as a blood vessel wall.

[0043] The hydrophilic monomer constituting the block copolymer is not particularly limited as long as it has the above-mentioned properties, and known compounds can be used, such as acrylamide and its derivatives, vinylpyrrolidone, acrylic acid, methacrylic acid and their derivatives, polyethylene glycol acrylate and its derivatives, monomers having sugars or phospholipids in the side chains, and water-soluble monomers such as maleic anhydride. More specifically, acrylic acid, methacrylic acid, N-methylacrylamide, N,N-dimethylacrylamide (DMAA), acrylamide, acryloylmorpholine, N,N-dimethylaminoethyl acrylate, N-vinylpyrrolidone, 2-methacryloyloxyethyl phosphorylcholine, 2-methacryloyloxyethyl-D-glycoside, 2-methacryloyloxyethyl-D-mannoside, vinyl methyl ether, 2-hydroxyethyl (meth)acrylate, 4-hydroxybutyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate, 6-hydroxyhexyl (meth)acrylate, 1,4-cyclohexanedimethanol mono(meth)acrylate, 1-chloro-2-hydroxypropyl (meth)acrylate, ) acrylate, diethylene glycol mono(meth)acrylate, 1,6-hexanediol mono(meth)acrylate, pentaerythritol tri(meth)acrylate, dipentaerythritol penta(meth)acrylate, neopentyl glycol mono(meth)acrylate, trimethylolpropane di(meth)acrylate, trimethylolethane di(meth)acrylate, 2-hydroxy-3-phenyloxypropyl (meth)acrylate, 4-hydroxycyclohexyl (meth)acrylate, 2-hydroxy-3-phenyloxy (meth)acrylate, cyclohexanedimethanol mono(meth)acrylate, poly(ethylene glycol) methyl ether acrylate, and poly(ethylene glycol) methyl ether methacrylate.From the viewpoints of imparting excellent lubricity (slidability), ease of synthesis, and operability, the hydrophilic monomer preferably includes at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone, and more preferably at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, and 2-hydroxyethyl methacrylate. Of these, from the viewpoint of excellent lubricity (slidability), N,N-dimethylacrylamide is particularly preferred as the hydrophilic monomer. In a preferred embodiment of the present invention, the hydrophilic monomer is a dialkylacrylamide. It is preferred that the carbon number of each dialkyl independently be 1 to 3.

[0044] The above hydrophilic monomers may be used alone or in combination of two or more. That is, the hydrophilic moiety derived from the hydrophilic monomer may be a homopolymer type composed of one hydrophilic monomer alone, or a copolymer type composed of two or more of the above hydrophilic monomers. When two or more types are used, the form of the hydrophilic moiety may be a block copolymer or a random copolymer, but a block copolymer is preferred.

[0045] That is, in a preferred embodiment of the present invention, the hydrophilic monomer includes at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone. In a more preferred embodiment of the present invention, the hydrophilic monomer is at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, and 2-hydroxyethyl methacrylate. In a particularly preferred embodiment of the present invention, the hydrophilic monomer is N,N-dimethylacrylamide.

[0046] The block copolymer has the above-mentioned structural unit (A) and structural unit (B). Here, the ratio of the structural unit (A) to the structural unit (B) is not particularly limited as long as the above-mentioned effects are achieved. Considering good lubricity (slidability), lubrication maintenance (slidability maintenance), coating layer strength, and bonding with the base layer, the ratio of the structural unit (A) to the structural unit (B) (molar ratio of structural unit (A): structural unit (B)) can be 1:2 to 1:100, 1:2 to 1:50, 1:5 to 1:50, 1:10 to 1:50, 1:20 to 1:50, 1:2 to 1:45, 1:5 to 1:45, 1:10 to 1:45, or 1:20 to 1:45. Within such a range, the surface lubricating layer can exhibit sufficient sliding properties due to the structural unit (B), and can exhibit sufficient coating layer strength, bonding with the base layer (in the case of a resin material), and durability due to the structural unit (A). The molar ratio of the structural unit (A):structural unit (B) can be controlled by adjusting the charge ratio (molar ratio) of each monomer in the production stage of the block copolymer. Therefore, the charge ratio (molar ratio) of the reactive monomer having an epoxy group to the hydrophilic monomer in the production stage of the block copolymer can be 1:2 to 1:100, 1:2 to 1:50, 1:5 to 1:50, 1:10 to 1:50, 1:20 to 1:50, 1:2 to 1:45, 1:5 to 1:45, 1:10 to 1:45, or 1:20 to 1:45. The molar ratio of the structural unit (A):structural unit (B) can be determined, for example, by NMR measurement ( １ H-NMR measurement, １３ This can be confirmed by performing spectroscopy (e.g., C-NMR measurement).

[0047] The block copolymer according to the present invention essentially contains the structural unit (A) and the structural unit (B), but may contain other structural units in addition to these structural units. When the block copolymer contains other structural units, examples of such other structural units include adipic acid, glutaric acid, triethylene glycol, and tripropylene glycol. The monomers constituting the other structural units may be used alone or in combination of two or more. That is, the other structural units may be homopolymers composed of a single structural unit, or copolymers composed of two or more structural units. When two or more monomers are used to constitute the other structural units, the segments composed of the monomers may be in the form of a block copolymer, a random copolymer, or an alternating copolymer.

[0048] When the block copolymer according to the present invention contains other structural units, the content of the other structural units is preferably more than 0 mol% and less than 5 mol% relative to all structural units constituting the block copolymer. That is, in the block copolymer according to the present invention, when the total of all structural units constituting the block copolymer is taken as 100 mol%, the total content of the structural units (A) and (B) is preferably 95 mol% or more (upper limit: less than 100 mol%). More preferably, the block copolymer according to the present invention is substantially composed of the structural units (A) and (B) (here, "substantially composed" in this specification means that the content of the other structural units is more than 0 mol% and less than 5 mol%). In this form, the block copolymer according to the present invention can achieve a good balance between the durability provided by the structural unit (A) and the lubricity (slidability) provided by the structural unit (B). Preferably, the block copolymer according to the present invention does not contain the other structural units (the content of the other structural units is 0 mol%).

[0049] The composition of each structural unit (structural units (A) and (B) and other structural units) can be measured by a known method. For example, １ The composition (molar ratio) of the structural units can be determined by measuring the integral ratio of the intensities of each signal in the H-NMR spectrum.

[0050] In one embodiment of the present invention, the block copolymer according to the present invention is composed essentially of, or consists only of, a structural unit (A) derived from at least one reactive monomer selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether, and a structural unit (B) derived from at least one hydrophilic monomer selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone.

[0051] In one embodiment of the present invention, the block copolymer according to the present invention is composed essentially of, or consists of, a structural unit (A) derived from at least one reactive monomer of glycidyl acrylate and glycidyl methacrylate, and a structural unit (B) derived from at least one hydrophilic monomer selected from the group consisting of N,N-dimethylacrylamide, acrylamide, and 2-hydroxyethyl methacrylate.

[0052] In one embodiment of the present invention, the block copolymer according to the present invention is composed essentially of, or consists of, a structural unit (A) derived from glycidyl methacrylate (a reactive monomer having an epoxy group) and a structural unit (B) derived from N,N-dimethylacrylamide (a hydrophilic monomer).

[0053] The weight-average molecular weight of the block copolymer is preferably 10,000 to 10,000,000 from the viewpoint of solubility. The weight-average molecular weight of the block copolymer is more preferably 100,000 to 5,000,000 from the viewpoint of ease of preparation of the 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.

[0054] The method for producing the block copolymer is not particularly limited, and can be produced by applying conventionally known polymerization methods such as living radical polymerization, polymerization using a macroinitiator, and polycondensation (e.g., the polymerization method described in JP-A-2014 / 162872). Of these, living radical polymerization or polymerization using a macroinitiator is preferred because it allows for easy control of the molecular weight and molecular weight distribution of the structural units (portions) derived from reactive 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 atom transfer radical polymerization (ATRP), which can be applied in the same manner or with appropriate modifications. Furthermore, in a polymerization method using a macroinitiator, for example, a macroinitiator having a reactive moiety with a reactive functional group and a radically polymerizable group such as a peroxide group is prepared, and then the macroinitiator is polymerized with a monomer for forming a hydrophilic moiety, thereby making it possible to prepare a block copolymer having a hydrophilic moiety and a reactive moiety.

[0055] After polymerization, the block copolymer is preferably purified by a common purification method such as reprecipitation, dialysis, ultrafiltration, or extraction.

[0056] <Hydrophobic Resin> The surface lubricating layer of the medical device of the present invention contains a hydrophobic resin. The hydrophobic resin induces ring-opening of epoxy groups present in the block copolymer. When the epoxy groups are ring-opened, cross-linking (bonding) between the block copolymers progresses. Furthermore, the medical device can maintain its shape well even after sliding. In particular, from the viewpoint of further achieving the above-mentioned effects, the hydrophobic resin is preferably one or more selected from polyvinyl chloride (PVC) resin and urethane resin, and more preferably polyvinyl chloride (PVC) resin. Here, vinyl chloride resin refers to poly(1-chloroethylene) as defined by the IUPAC nomenclature. As long as it contains mainly poly(1-chloroethylene), commercially available soft vinyl chloride resin or hard vinyl chloride resin may be used. To ensure consistent performance, reagent-grade vinyl chloride resin (PVC) with a poly(1-chloroethylene) content of 100% or less is preferred, and vinyl chloride resin substantially free of plasticizers and additives is particularly preferred. Here, "a vinyl chloride resin that is substantially free of plasticizers and additives" means that the vinyl chloride resin does not contain any plasticizers or additives (below the detection limit), or that the vinyl chloride resin contains plasticizers or additives in a total amount of 10 ppm by mass or less. The vinyl chloride resin (PVC) may contain structural units derived from vinyl chloride (1-chloroethylene). In other words, it may be a homopolymer consisting solely of vinyl chloride (1-chloroethylene), or a copolymer containing structural units derived from monomers other than vinyl chloride (1-chloroethylene). However, considering sliding properties and durability, a homopolymer is preferred. Therefore, according to one embodiment of the present invention, the vinyl chloride resin is a homopolymer consisting of structural units derived from vinyl chloride (1-chloroethylene) and is substantially free of plasticizers and additives.

[0057] In this specification, the hydrophobic resin is preferably insoluble in water, and "insoluble in water" refers to a substance that is insoluble (or poorly soluble) in water at room temperature (23°C) and under normal pressure (1 atmosphere). For example, this refers to a substance that dissolves less than 1 g in 100 ml of water at room temperature and normal pressure, but is not limited thereto.

[0058] The hydrophobic resin contained in the surface lubricating layer according to one embodiment of the present invention preferably contains at least a vinyl chloride resin, and more preferably a vinyl chloride resin. That is, the surface lubricating layer according to one embodiment of the present invention contains a vinyl chloride resin, which improves the film strength of the surface lubricating layer and further enhances its durability. This is presumed to be due to the following mechanism. In a block copolymer containing epoxy groups, the epoxy groups undergo ring-opening, which promotes crosslinking (bonding) between the block copolymers and increases the film strength of the surface lubricating layer. Therefore, by coexisting the block copolymer, preferably with a small amount of vinyl chloride resin, the chlorine contained in the vinyl chloride resin is released (dechlorinated) from the vinyl chloride resin, promoting the ring-opening of the epoxy groups in the block copolymer. This allows for faster ring-opening and crosslinking of the epoxy groups compared to when vinyl chloride resin is not present, resulting in a lower thermal load on the substrate and the surface lubricating layer, such as shorter heating time and lower heating temperature. The shorter heating time reduces working time and energy consumption, thereby reducing costs and increasing the film strength of the block copolymer. Note that the above mechanism is presumed and is not limited thereto.

[0059] The weight average molecular weight (Mw) of the hydrophobic resin is preferably 1,000 or more, more preferably 10,000 or more, and even more preferably 30,000 or more. The weight average molecular weight of the hydrophobic resin is preferably 10,000,000 or less, more preferably 500,000 or less, and even more preferably 250,000 or less. As an example, the weight average molecular weight (Mw) of the hydrophobic resin is preferably 1,000 to 10,000,000, more preferably 10,000 to 500,000, and even more preferably 30,000 to 250,000. Having the weight average molecular weight (Mw) of the hydrophobic resin within the above range promotes crosslinking (bonding) between block copolymers, further improving the stability of the surface lubrication layer.

[0060] In one embodiment of the medical device, the content (mass%) of the hydrophobic resin in the surface lubricating layer is preferably less than the content (mass%) of the block copolymer. This results in lower friction resistance and better sliding properties. More specifically, the mixing ratio of the block copolymer and the hydrophobic resin (block copolymer: hydrophobic resin (mass ratio)) is, for example, 100:0.01 or more and less than 100:100, preferably 100:0.1 or more and 100:90 or less, more preferably 100:0.25 or more and 100:70 or less, even more preferably 100:0.5 or more and 100:50 or less, and particularly preferably 100:1 or more and 100:10 or less. If the mass ratio of the block copolymer and the hydrophobic resin is within the above range, the durability and lubricity (slidability) of the obtained surface lubricating layer can be fully exhibited. Although it is possible to apply a separate coating with lubricity, the medical device formed using the medical material of the present invention (which includes a coating layer made of the medical material in part) has slipperiness (sliding property, lubricity), and therefore there is no need to apply a separate coating with lubricity.

[0061] (Standard deviation of R value) In the medical device according to the present invention, the standard deviation of the R value of the surface lubricating layer stained with Congo red solution, measured by the measurement method described in the Examples, is 10 or less. When the standard deviation of the R value is 10 or less, the medical device according to the present invention has excellent both sliding properties and durability. The standard deviation of the R value of the surface lubricating layer can be calculated according to the method described in the Examples.

[0062] The standard deviation of the R value is an index for evaluating the uneven distribution of the surface lubricant layer on the substrate surface, in other words, an index for evaluating the variation in the thickness of the surface lubricant layer.Here, the large variation in the thickness of the surface lubricant layer means that the thickness of the surface lubricant layer 2 is not constant, as shown in Figure 2, and the difference in thickness between the thick part and the thin part of the surface lubricant layer is large, and the small variation in the thickness of the surface lubricant layer means that the thickness of the surface lubricant layer is relatively constant, as shown in Figure 1, and the difference in thickness between the thick part and the thin part of the surface lubricant layer is relatively small.When the standard deviation of the R value of the surface lubricant layer is 10 or less, it indicates that the variation in the thickness of the surface lubricant layer is small.

[0063] Generally, a thick surface lubricating layer has excellent sliding properties (i.e., low sliding resistance) and high durability, while a thin layer has poor sliding properties (i.e., high sliding resistance) and low durability. When the standard deviation of the R value is greater than 10, i.e., when the thickness of the surface lubricating layer varies greatly, the surface lubricating layer will have a mixture of parts with high sliding properties and durability and parts with low sliding properties and durability. When a medical device having such a surface lubricating layer is used, forces (e.g., forces due to external friction) are likely to be applied to the thin layer parts with poor sliding properties. Furthermore, since the thin layer parts are also poor in durability, the surface lubricating layer may deteriorate or be damaged. For these reasons, a medical device having a surface lubricating layer with a large variation in thickness will have poor sliding properties and durability. On the other hand, when the standard deviation of the R value is 10 or less, i.e., when the thickness of the surface lubricating layer varies little, this phenomenon does not occur. In the case of a surface lubricating layer with little variation in thickness, the thickness of the layer is constant, so there are no (or few) areas where the sliding property is lower than the surrounding area, and the phenomenon of localized force being applied due to differences in sliding property is unlikely to occur.In addition, there are no (or few) areas where the durability is inferior to the surrounding area, so it is thought that the durability of the medical device is unlikely to be reduced due to the deterioration or damage of a part of the surface lubricating layer.Therefore, a medical device according to one embodiment of the present invention, in which the standard deviation of the R value is 10 or less, has excellent sliding property and excellent durability.

[0064] In the medical device according to the present invention, the standard deviation of the R value of the surface lubricating layer stained with Congo red solution is 10 or less, and in one embodiment, the R value is preferably less than 10, more preferably 9.5 or less, and even more preferably 9.0 or less. The lower limit of the R value is not particularly limited, but may be 0 or more, 1 or more, or 2 or more. By having the R value of the surface lubricating layer in the above range, the variation in the thickness of the surface lubricating layer becomes smaller, thereby further improving the sliding properties and durability of the medical device.

[0065] (Sliding resistance) In the medical device according to one embodiment, the sliding resistance value of the surface lubricating layer when sliding 10 times in the sliding resistance test is preferably 8.5 gf or less, more preferably 7.5 gf or less, even more preferably 6.5 gf or less, even more preferably 6 gf or less, particularly preferably 5.5 gf or less, and most preferably 5 gf or less.In addition, in the medical device according to one embodiment, the lower limit of the sliding resistance value of the surface lubricating layer is not particularly limited, but is preferably 0.5 gf or more.By the sliding resistance value of the surface lubricating layer being in the above range, the sliding property of the medical device is also suitable, and furthermore, the durability of the medical device is also improved.The sliding resistance value of the surface lubricating layer can be calculated according to the "sliding resistance test" described in the examples.

[0066] (Durability (increase in sliding resistance)) In one embodiment of the medical device, the increase in sliding resistance in a durability test of the surface lubricating layer is preferably less than 15 gf, more preferably 10 gf or less, even more preferably 5 gf or less, even more preferably 2.5 gf or less, particularly preferably 1 gf or less, and most preferably 0 gf. Furthermore, in one embodiment of the medical device, the lower limit of the increase in sliding resistance in a durability test of the surface lubricating layer is not particularly limited, and is, for example, 0 gf. When the increase in sliding resistance of the surface lubricating layer is within the above range, the durability as a medical device becomes more sufficient. The increase in sliding resistance in a durability test of the surface lubricating layer can be calculated according to the "Durability Test" described in the Examples.

[0067] (Unevenness of the surface of the surface lubricating layer) In one embodiment of the medical device, the less unevenness (also called bumpy feeling) of the surface of the surface lubricating layer of the surface lubricating layer, the better. The less unevenness, the less unevenness of the surface lubricating layer, and the more suitable it becomes as a medical device. The unevenness of the surface of the surface lubricating layer can be evaluated according to the method described in "Evaluation of the unevenness of the surface of the surface lubricating layer" in the examples.

[0068] (Dynamic Friction Resistance Value) In one embodiment of the medical device, the dynamic friction resistance value (0°) at the 5th time, the dynamic friction resistance value (0°) at the 50th time, the dynamic friction resistance value (180°) at the 5th time, and the dynamic friction resistance value (180°) at the 50th time are all preferably 10 gf or less, more preferably 5 gf or less, even more preferably 4 gf or less, particularly preferably 3 gf or less, and most preferably 2.5 gf or less. Furthermore, the lower limits of the dynamic friction resistance value (0°) at the 5th time, the dynamic friction resistance value (0°) at the 50th time, the dynamic friction resistance value (180°) at the 5th time, and the dynamic friction resistance value (180°) at the 50th time are not particularly limited, but are preferably 0.1 gf or more. When the dynamic friction resistance value (0°) at the 5th time, the dynamic friction resistance value (0°) at the 50th time, the dynamic friction resistance value (180°) at the 5th time, and the dynamic friction resistance value (180°) at the 50th time are all within the above ranges, the slidability of the medical device becomes favorable and the durability of the medical device is also improved.

[0069] Furthermore, in one embodiment of the medical device, the difference (absolute value) between the kinetic friction resistance value (0°) at the fifth time and the kinetic friction resistance value (0°) at the fiftieth time, and the difference (absolute value) between the kinetic friction resistance value (180°) at the fifth time and the kinetic friction resistance value (180°) at the fiftieth time are both preferably 10 gf or less, more preferably 5 gf or less, even more preferably 2.5 gf or less, particularly preferably 1 gf or less, and most preferably 0.75 gf or less. Furthermore, the lower limit of the difference (absolute value) between the kinetic friction resistance value (0°) at the fifth time and the kinetic friction resistance value (0°) at the fiftieth time, and the difference (absolute value) between the kinetic friction resistance value (180°) at the fifth time and the kinetic friction resistance value (180°) at the fiftieth time, are not particularly limited, but are preferably 0.01 gf or more. When the difference (absolute value) between the dynamic friction resistance value (0°) at the fifth time and the dynamic friction resistance value (0°) at the fiftieth time, and the difference (absolute value) between the dynamic friction resistance value (180°) at the fifth time and the dynamic friction resistance value (180°) at the fiftieth time are within the above-mentioned ranges, the slidability of the medical device is favorable and the durability of the medical device is also improved.

[0070] In addition, in the medical device according to one embodiment, the difference (absolute value) between the 5th dynamic friction resistance value (0°) and the 5th dynamic friction resistance value (180°) in the surface lubrication layer, and the difference (absolute value) between the 50th dynamic friction resistance value (0°) and the 50th dynamic friction resistance value (180°) are preferably 5 gf or less, more preferably 1 gf or less, even more preferably 0.5 gf or less, particularly preferably 0.25 gf or less, and most preferably 0.15 gf or less. In addition, the lower limit of the difference (absolute value) between the 5th dynamic friction resistance value (0°) and the 5th dynamic friction resistance value (180°) in the surface lubrication layer, and the difference (absolute value) between the 50th dynamic friction resistance value (0°) and the 50th dynamic friction resistance value (180°) are not particularly limited, but are preferably 0.01 gf or more. When the difference (absolute value) between the dynamic friction resistance value (0°) at the fifth time and the dynamic friction resistance value (180°) at the fifth time in the surface lubrication layer, and the difference (absolute value) between the dynamic friction resistance value (0°) at the 50th time and the dynamic friction resistance value (180°) at the 50th time are both within the above ranges, the sliding properties of the medical device are also favorable, and the durability of the medical device is also improved.

[0071] The dynamic friction resistance value (0°) at the fifth time, the dynamic friction resistance value (0°) at the fiftieth time, the dynamic friction resistance value (180°) at the fifth time, and the dynamic friction resistance value (180°) at the fiftieth time can be evaluated according to the method described in "Measurement of Dynamic Friction Resistance Value" in the Examples.

[0072] [Method for manufacturing a medical device] Another aspect of the present invention provides a method for manufacturing a medical device comprising a base layer and a surface lubricating layer supported on at least a portion of the base layer, wherein the surface lubricating layer comprises a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, and a hydrophobic resin, and the standard deviation of the R value of the surface lubricating layer stained with Congo red solution is 10 or less. Hereinafter, the method for manufacturing a medical device having the above configuration will be referred to as a "manufacturing method according to one embodiment" or simply as a "manufacturing method".

[0073] A manufacturing method according to one embodiment includes the steps of: preparing a coating liquid containing a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, a hydrophobic resin, and a solvent ((I) preparation step); applying the coating liquid onto a substrate layer ((II) application step); and heat treating the substrate to which the coating liquid has been applied ((III) heat treatment step). A medical device obtained by this manufacturing method not only has excellent sliding properties but also durability against loads such as abrasion and abrasion.

[0074] In other words, the medical device according to one embodiment of the present invention is a medical device manufactured by a manufacturing method including the steps of: preparing a coating liquid containing a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, a hydrophobic resin, and a solvent ((I) preparation step); applying the coating liquid onto a substrate layer ((II) application step); and heat treating the substrate to which the coating liquid has been applied ((III) heat treatment step).

[0075] In the method for producing a medical device according to one embodiment of the present invention, the terms block copolymer, hydrophobic resin, base layer, etc. are the same as those described in the above sections, and therefore will not be explained here.

[0076] (I) Preparation Step: In this step, a coating liquid containing a block copolymer, a hydrophobic resin, and a solvent is prepared. Here, in this step, the coating liquid may be prepared by mixing the block copolymer, the hydrophobic resin, and the solvent to prepare the coating liquid. Alternatively, a coating liquid containing the block copolymer, the hydrophobic resin, and the solvent may be purchased and used.

[0077] A preferred embodiment of preparing a coating liquid by mixing a block copolymer, a hydrophobic resin, and a solvent will be described in detail below.

[0078] (Preparation of Coating Solution) A coating solution is prepared using the above-mentioned block copolymer, hydrophobic resin, and solvent. Furthermore, in the coating solution (at room temperature), PVC is stable and dechlorination reaction does not occur. Therefore, in the solution state, ring-opening of the epoxy group (crosslinking reaction) hardly or not at all occurs, and the viscosity of the coating solution hardly or not at all changes. Therefore, it is easy to work with.

[0079] The order and method of adding the block copolymer, hydrophobic resin, and solvent are not particularly limited. The components may be added all at once or separately, stepwise, or continuously. The mixing method is also not particularly limited, and known methods can be used. Methods for preparing the coating liquid include sequentially adding the hydrophobic resin and block copolymer to a solvent, sequentially adding the block copolymer and hydrophobic resin to a solvent, or simultaneously adding the hydrophobic resin and block copolymer to a solvent. Preferably, the hydrophobic resin and block copolymer are sequentially added to a solvent, or the block copolymer and hydrophobic resin are sequentially added to a solvent. The addition may be carried out with stirring, if necessary. Alternatively, the mixed solution may be stirred after the addition.

[0080] The solvent used to prepare the coating liquid is not particularly limited as long as it can dissolve the block copolymer and hydrophobic resin (and other components, if used), and is appropriately selected depending on the type of block copolymer and hydrophobic resin (and other components, if used). From the viewpoint of high solubility, alcoholic solvents such as methanol, ethanol, isopropyl alcohol, and butanol; and organic solvents such as dichloromethane, chloroform, carbon tetrachloride, tetrahydrofuran (THF), dimethyl sulfoxide, N,N-dimethylformamide (DMF), dioxane, and benzene are preferably used. These solvents may be used alone or in combination (in the form of a mixed solvent) of two or more types.

[0081] Among the above, the solvent used for preparing the coating solution preferably contains one or more selected from the group consisting of tetrahydrofuran (THF), N,N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO), and more preferably contains one or more selected from the group consisting of tetrahydrofuran (THF) and N,N-dimethylformamide (DMF).

[0082] Furthermore, when two or more solvents are combined to prepare the coating solution, it is preferable that all of the two or more solvents be capable of dissolving the hydrophobic resin, and that the two or more solvents contain both a good solvent and a poor solvent for the block copolymer. Examples of good solvents with high solubility for the block copolymer include N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO). Examples of poor solvents with relatively low solubility for the block copolymer include tetrahydrofuran (THF). It is particularly preferable that the solvent used to prepare the coating solution contains both N,N-dimethylformamide (DMF) and tetrahydrofuran (THF). By including a good solvent and a poor solvent in the solvent used to prepare the coating solution, variation in the thickness of the surface lubricating layer can be suppressed. This is thought to be because, by including a good solvent and a poor solvent in the solvent, the viscosity of the prepared coating solution can be maintained relatively low even when the concentration of the block copolymer in the coating solution is increased. Generally, block copolymers used for coating layers (such as surface lubricating layers) with high sliding properties have long hydrophilic group molecular chains and large molecular weights. Therefore, increasing the concentration of the block copolymer in the coating solution tends to increase the viscosity of the coating solution. Therefore, in order to make a uniform solution of the block copolymer suitable for manufacturing methods such as immersion and spraying, it is necessary to lower the concentration of the block copolymer. If the concentration of the block copolymer in the coating solution is low, it is difficult to obtain a thick coating layer (such as a surface lubricating layer) during film formation. Furthermore, if the concentration is low, the molecular chains of the hydrophilic groups of the block copolymer spread widely in the coating solution, and the molecular chains of the hydrophilic groups become entangled during the heating and drying processes, which is thought to easily cause uneven distribution (uneven thickness) of the coating layer (such as a surface lubricating layer). In contrast, a coating solution with a high concentration of block copolymer and low viscosity can be suitably used in manufacturing methods such as immersion and spraying, and it is easy to obtain a thick coating layer during film formation. Furthermore, the molecular chains of the hydrophilic groups of the block copolymer spread relatively little in the coating solution, and the molecular chains are less likely to become entangled during the heating and drying processes, which is thought to prevent uneven distribution (uneven thickness) of the coating layer (such as a surface lubricating layer).The above mechanism is speculation and does not limit the invention.

[0083] When the solvent used to prepare the coating liquid contains both tetrahydrofuran (THF) and N,N-dimethylformamide (DMF), the mixing ratio (mass ratio) of tetrahydrofuran (THF) to N,N-dimethylformamide (DMF) may be appropriately adjusted so as to obtain the desired sliding properties and durability, and is not particularly limited. However, in order to uniformly mix the polymer, the mass ratio of N,N-dimethylformamide (DMF) to tetrahydrofuran (THF) is, for example, 0.5 or more, 0.8 or more, 1.0 or more, 3.0 or more, 5.0 or more, 7.0 or more, or 9.0 or more. Furthermore, this mass ratio is, for example, 20.0 or less, 15.0 or less, 10.0 or less, 8.0 or less, 6.0 or less, 4.0 or less, or 2.0 or less.

[0084] The concentration of the block copolymer in the coating solution is not particularly limited. From the viewpoint of further improving the coatability, the slidability, and durability of the surface lubricant layer, the concentration of the block copolymer in the coating solution is preferably 0.5 to 20% by mass, more preferably 1 to 15% by mass, even more preferably 3 to 10% by mass, and particularly preferably greater than 3% by mass and 8% by mass or less, with 5% by mass being used in the examples. If the concentration of the block copolymer is within the above range, the slidability and durability of the resulting surface lubricant layer can be fully exhibited. Furthermore, a uniform surface lubricant 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.

[0085] The concentration of the hydrophobic resin in the coating solution is also not particularly limited. From the viewpoint of the lubricity (slidability) of the surface lubrication layer, it is preferable to add a small amount of hydrophobic resin. On the other hand, from the viewpoint of the durability (sliding durability) of the surface lubrication layer, it is preferable to add a certain amount of hydrophobic resin. From the above viewpoints, the concentration of the hydrophobic resin in the coating solution is preferably 0.001% by mass or more and less than 12% by mass, more preferably 0.005% by mass or more and less than 4.0% by mass, even more preferably 0.01% by mass or more and less than 0.5% by mass, particularly preferably 0.01 to 0.2% by mass, and in the embodiment, it is 0.1% by mass. If the concentration of the hydrophobic resin is within the above range, the lubricity (slidability) of the surface lubrication layer is sufficiently ensured, while the crosslinking of the block copolymer is sufficiently promoted without excessively progressing (crosslinking can be moderately promoted). Therefore, the lubricity (slidability) and durability of the obtained surface lubrication layer can be fully exhibited. However, even if it is outside the above range, it can be fully used as long as it does not affect the effects of the present invention.

[0086] In addition, from the viewpoint of further improving durability (sliding durability), coating property, lubricity (sliding property) of the surface lubrication layer, etc., the content (mass%) of the hydrophobic resin in the coating liquid is preferably less than the content (mass%) of the block copolymer. More specifically, the mixing ratio of the block copolymer and the hydrophobic resin (block copolymer: hydrophobic resin (mass ratio)) can be the mass ratio described in the above-mentioned "surface lubrication layer".

[0087] (II) Coating Step In this step, the coating liquid prepared in the above (I) Preparation Step is applied onto the substrate layer to form a coating film (coating layer) on the substrate layer.

[0088] The method for applying (coating) the coating liquid to the substrate layer is not particularly limited, and any conventionally known method can be used, such as a coating / printing method, a dipping method (dipping method, dip coating method), a spraying method (spray method), a spin coating method, a mixed solution impregnated sponge coating method, a bar coating method, a die coating method, a reverse coating method, a comma coating method, a gravure coating method, a doctor knife method, etc. Of these, the dipping method (dipping method, dip coating method) is preferably used.

[0089] When the immersion method is used, the speed at which the catheter substrate is immersed in the coating solution and then pulled up is not particularly limited, but is preferably 1 mm / sec to 30 mm / sec, more preferably 2 mm / sec to 20 mm / sec, and even more preferably 2.5 mm / sec to 15 mm / sec. By keeping the pulling speed within the above range, a desired amount of coating solution can be applied to the outer surface of the catheter substrate.

[0090] When forming a surface lubricating layer on a thin and narrow inner surface of a catheter, guide wire, injection needle, etc., the substrate layer may be immersed in the coating solution and the pressure in the system may be reduced to degas the solution. By reducing the pressure and degassing the solution, the solution can be quickly penetrated into the thin and narrow inner surface, facilitating the formation of the surface lubricating layer.

[0091] Furthermore, when forming a surface lubricating layer only on a portion of the substrate layer, only a portion of the substrate layer can be immersed in a coating liquid and the coating liquid can be coated onto that portion of the substrate layer, thereby forming a surface lubricating layer on the desired surface portion of the substrate layer.

[0092] In addition, when the structure of a medical device requires that both the outer and inner surfaces of a cylindrical device have a surface lubricating layer, the immersion method (dipping method) is preferably used because it allows both the outer and inner surfaces to be coated at the same time.

[0093] The amount of coating liquid applied is preferably such that the thickness (film thickness) of the resulting coating (surface lubricating layer) is 0.1 to 10 μm, more preferably 0.5 to 5 μm, and even more preferably 1 to 3 μm, and in the example, 1.5 μm. If the amount applied is such that the thickness of the coating (surface lubricating layer) is 0.1 μm or more, the durability of the resulting coating (surface lubricating layer) can be sufficiently achieved. Furthermore, if the amount applied is such that the thickness of the coating (surface lubricating layer) is 10 μm or less, the surface of the coating (surface lubricating layer) becomes less sticky, making it easier to handle during production.

[0094] (III) Heat Treatment Step The manufacturing method of a medical device according to one embodiment includes the step of applying a coating liquid to the substrate layer of the medical device in the above-mentioned (II) coating step to form a coating film (coating layer), and then subjecting the substrate to a heat treatment. In other words, a medical device according to one embodiment of the present invention can be produced by a manufacturing method including the step of applying a coating liquid to the substrate layer in the above-mentioned coating step to form a coating film (coating layer), and then subjecting the substrate to a heat treatment. By subjecting the surface lubricating layer to heat treatment, the surface lubricating layer has both excellent durability and sliding properties, and the durability and sliding properties of the medical device are also excellent.

[0095] The range of the heating temperature in the heat treatment step according to one embodiment is not particularly limited, but is preferably 50° C. to 200° C., more preferably 90° C. to 180° C., and in the example, 130° C. By maintaining (heat treating) within such a temperature range, a strong surface lubricating layer is formed.

[0096] The heating time in the heat treatment step according to one embodiment is not particularly limited, but is preferably 15 minutes to 20 hours, more preferably 30 minutes to 12 hours, and even more preferably 45 minutes to 6 hours, and in the examples, it is 1 hour or 3 hours. By setting the heating time in this manner, the crosslinking reaction in the block copolymer is effectively promoted, and a stronger coating layer (surface lubricating layer) is formed, so that high surface lubricity (slidability) can be maintained for a longer period of time.

[0097] In one embodiment of the manufacturing method, in the heat treatment step, the heat treatment may be performed by gradually increasing the heating temperature. By performing the heat treatment by gradually increasing the heating temperature, the durability and surface lubricity (slidability) of the surface lubricating layer and the medical device become more excellent.

[0098] Here, the heat treatment "increasing the temperature stepwise" preferably includes a step of maintaining a predetermined heating temperature for a certain period of time and a step of increasing the temperature to the predetermined heating temperature without stopping the increase. In addition, the heat treatment "increasing the temperature stepwise" in one embodiment preferably includes a step of maintaining a predetermined heating temperature for a certain period of time and a step of increasing the temperature to the predetermined heating temperature without stopping the increase.

[0099] (IV) Other Steps: In one embodiment of the production method, a drying step may be included before the heat treatment step. In the drying step, excess solvent is removed, allowing the subsequent heat treatment step to proceed more efficiently. The temperature of the drying step is not particularly limited, but is preferably 10°C or higher and lower than 50°C, and more preferably 20 to 30°C. The drying time is also not particularly limited, but is preferably 15 minutes to 20 hours, more preferably 30 minutes to 12 hours. The pressure conditions during drying are also not particularly limited, and drying can be performed under normal pressure (atmospheric pressure), or under increased or reduced pressure.

[0100] The heating step and the drying step can be carried out by using, for example, an oven, a vacuum dryer, etc. When the drying step is carried out by natural drying, no special drying means (device) is required.

[0101] [Muddle Measurement Method] One aspect of the present invention is a maldistribution measurement method for evaluating the maldistribution of a surface lubricating layer in a medical device having a surface lubricating layer by the standard deviation of the R value of the surface lubricating layer stained with Congo red solution. This method can evaluate the maldistribution of the surface lubricating layer in the base layer of the medical device, i.e., the variation in the thickness of the surface lubricating layer. If the standard deviation of the R value of the surface lubricating layer measured by this maldistribution measurement method is 10 or less, it can be evaluated that the surface lubricating layer has little maldistribution, i.e., little variation in the thickness of the surface lubricating layer. A medical device evaluated in this manner can be evaluated as having excellent sliding properties and durability. The standard deviation of the R value of the surface lubricating layer can be calculated according to the method described in "Standard Deviation of the R Value of the Surface Lubricating Layer" in the Examples.

[0102] [Uses of Medical Devices] The medical devices produced by the method of the present invention are devices used in contact with body fluids, blood, etc., and have a surface that is slidable in body fluids, aqueous liquids such as physiological saline, thereby improving operability and reducing damage to tissue mucosa. Specific examples include catheters, guidewires, indwelling needles, etc. used in blood vessels, but other examples include the following medical devices.

[0103] (a) Catheters that are inserted or left in the digestive tract via the mouth or nose, such as gastric catheters, nutritional catheters, and enteral feeding tubes.

[0104] (b) Catheters that are inserted or placed in the airway or trachea via the mouth or nose, such as oxygen catheters, oxygen cannulas, endotracheal tubes and cuffs, tracheostomy tubes and cuffs, and endotracheal suction catheters.

[0105] (c) Catheters that are inserted or placed in the urethra or ureter, such as urethral catheters, urinary catheters, and urethral balloon catheters.

[0106] (d) Catheters such as suction catheters, drainage catheters, and rectal catheters that are inserted or left in various body cavities, organs, or tissues.

[0107] (e) Catheters that are inserted or placed in blood vessels, such as indwelling needles, IVH catheters, thermodilution catheters, angiography catheters, vasodilator catheters, and dilators or introducers, or guide wires and stylets for these catheters.

[0108] (f) Artificial trachea, artificial bronchi, etc.

[0109] (g) Medical devices for extracorporeal circulation therapy (artificial lungs, artificial hearts, artificial kidneys, etc.) and their circuits.

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

[0111] Synthesis Example 1 The following reaction was carried out to produce a block copolymer (1).

[0112]

[0113] 29.7 g of triethylene glycol was added dropwise to 72.3 g of adipic acid dichloride at 50°C, and then the hydrochloric acid was removed under reduced pressure at 50°C for 3 hours to obtain an oligoester. Next, 4.5 g of methyl ethyl ketone was added to 22.5 g of the obtained oligoester, and this was added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of dioctyl phosphate as a surfactant, and 120 g of water, and the reaction was carried out at -5°C for 20 minutes. The obtained product was repeatedly washed with water and methanol and then dried to obtain a polyperoxide (PPO) having multiple peroxide groups in the molecule.

[0114] Next, 0.5 g of this PPO, 9.5 g of glycidyl methacrylate (GMA), and 30 g of benzene as a solvent were polymerized at 80°C for 2 hours with stirring under reduced pressure. The reaction product obtained after the polymerization was reprecipitated with diethyl ether to obtain polyglycidyl methacrylate (PPO-GMA) having multiple peroxide groups in the molecule.

[0115] Subsequently, 0.42 g of the obtained PPO-GMA (corresponding to 3.0 mmol of GMA) was dissolved in chlorobenzene together with 10.0 g (101 mmol) of N,N-dimethylacrylamide (DMAA) as a polymerization initiator, and the solution was heated to 75°C for 7 hours under a nitrogen atmosphere to polymerize, thereby obtaining block copolymer (1). The DMAA:GMA ratio of the produced block copolymer (1) was １Measurement by H-NMR revealed that the ratio of DMAA:GMA (i.e., the molar ratio of hydrophilic moieties to hydrophobic moieties in the block copolymer) was 35:1 (molar ratio). Furthermore, the viscosity of a 1 wt % chloroform solution of the obtained block copolymer (1) was measured at 30°C using a B-type rotational viscometer (manufactured by Brooksfield, device name: DV-I Prime), and was found to be 11.8 mPa s.

[0116] Example 1 Polyvinyl chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Mw = 50,000 or more) was dissolved in a mixed solvent of N,N-dimethylformamide (DMF) and tetrahydrofuran (THF) (DMF:THF = 1:1 (mass ratio)) so that the final concentration in the coating solution would be 0.1 mass% (shown as mixed solution (1) in Table 1). The block copolymer (1) synthesized in Synthesis Example 1 above was added to and dissolved in the mixed solution (1) so that the final concentration in the coating solution would be 5 mass% to prepare coating solution (1).

[0117] A tube (outer diameter: 2.80 mm) made of nylon elastomer (Vestamid E47-S1, manufactured by Evonik) as a substrate layer was immersed in the coating liquid (1), pulled upward at a pulling rate of 5 mm / sec, and dried at room temperature (25 ° C) for 1 hour to form a coating film on the tube surface. Furthermore, the tube on which this coating film was formed (coated tube (1)) was placed in an oven, and the temperature inside the oven was increased from room temperature to 130 ° C without stopping the temperature increase. After that, it was stored at 130 ° C for 1 hour for heat treatment, and by removing it from the oven, a coating layer (surface lubricating layer) (film thickness: 1.5 μm) containing a cross-linked copolymer derived from a block copolymer on the surface was prepared. Sample (1) of Example 1 was prepared.

[0118] Comparative Example 1 The block copolymer synthesized in Synthesis Example 1 above was added to and dissolved in N,N-dimethylformamide (DMF) so that the final concentration in the coating liquid would be 3% by mass, to prepare a coating liquid.

[0119] A tube (outer diameter: 2.46 mm) made of polyester elastomer (manufactured by Toyobo MC, Pelprene E-450B) as a substrate layer was immersed in the coating solution, pulled up at a pulling rate of 5 mm / sec, and dried at room temperature (25 ° C) for 1 hour to form a coating film on the tube surface. Furthermore, the tube on which this coating film was formed (coated tube (2)) was placed in an oven, and the temperature inside the oven was increased to 130 ° C without stopping the temperature increase, and then stored at 130 ° C for 3 hours, thereby performing a heat treatment. The tube was then removed from the oven and had a coating layer (surface lubrication layer) (film thickness: 0.5 μm to 1.0 μm) containing a cross-linked copolymer derived from a block copolymer on the surface. A sample of Comparative Example 1 (Comparative Sample (1)) was prepared.

[0120] Comparative Example 2 The block copolymer synthesized in Synthesis Example 1 above was added to and dissolved in N,N-dimethylformamide (DMF) so that the final concentration in the coating liquid would be 5% by mass, to prepare a coating liquid.

[0121] A sample of Comparative Example 2 (Comparative Sample (2)) was produced in the same manner as in Comparative Example 1, except that the substrate layer was a tube (outer diameter: 2.80 mm) made of nylon elastomer (Vestamid E47-S1, manufactured by Evonik), the tube on which the coating film had been formed (coated tube (3)) was placed in an oven, the temperature in the oven was increased to 130°C without stopping the temperature increase, and then the tube was stored at 130°C for 1 hour.

[0122] [Standard deviation of R value of surface lubrication layer] For the sample (1) prepared in the above-mentioned Example 1 and the comparative samples (1) and (2) prepared in the above-mentioned Comparative Examples 1 and 2 (hereinafter, each of sample (1), comparative sample (1) and comparative sample (2) will also be simply referred to as "sample"), the standard deviation of the R value of the surface lubrication layer was measured and calculated according to the following method. The results are shown in Table 1.

[0123] <Staining Method> Each sample was stained using the following staining method. 1. Congo red reagent (Congo red, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was dissolved in RO water to a concentration of 2% by mass to prepare a staining solution. 2. The sample was immersed in the staining solution for 2 minutes. 3. The sample was removed from the staining solution and rinsed with running water (tap water) for 1 minute. 4. The sample was dried. Drying was performed by air drying or vacuum drying.

[0124] <Photographing method> Each sample stained by the above staining method was photographed using a digital microscope according to the following photographing method. 1. The illuminance, lens magnification, and other conditions for photography were fixed. Device name: DSX1000 (manufactured by Evident) Objective lens: DSX10-XLOB10X Total magnification: 164x Observation method: Simple polarized coaxial epi-illumination: 10000 PO: 90 ISO sensitivity: 400 Image size: 1200 x 1200.

[0125] Since the upper and lower parts of the field of view were outside the focal depth and the image was blurred when photographing the tube, the upper and lower parts were cut off from the photographed image (1200 x 1200) and resized (1200 x 675). 2. The sample was fixed so that its central axis was approximately horizontal, and the camera was fixed at a position 50 mm away, midway between the 100 mm coating. 3. The sample was adjusted so that it was at the center of the photographed image, the focus was adjusted, and an image was acquired. This image was designated the 0° image. 4. The sample was rotated 90° circumferentially around the central axis, and an image was acquired in the same manner as in 1. to 3. above. This image was designated the 90° image. 5. The sample was rotated another 90° circumferentially around the central axis, and an image was acquired in the same manner as in 1. to 3. above. This image was designated the 180° image. 6. The sample was rotated another 90° circumferentially around the central axis, and an image was acquired in the same manner as in 1. to 3. above. The image was taken as a 270° image.

[0126] <Method of Calculating Average R Value and Standard Deviation of R Value> From each image captured and acquired by the above-described photographing method, the average R value and standard deviation of the R value of each sample were calculated by the following method.

[0127] [CSV Data Output] CSV data was obtained for the 0°, 90°, 180°, and 270° images of each sample according to the following procedure. 1. Image data (.jpg) was opened using the image processing software "ImageJ" (free software, downloadable from the following URL: https: / / imagej.net / Welcome). 2. "Histogram" was selected under the "Analyze" tab. 3. In the displayed histogram, "RGB" was selected so that the histogram would show only Red. 4. The "List" button was selected, and "Save As" under the "File" tab was selected to output the data in CSV format.

[0128] Calculation of the average R value Based on the CSV data output above, the average R value of each sample was calculated. Here, in the CSV data, value indicates the R value (0 to 255), and count indicates the number of each R value (number of pixels) in the image data. 1. The count data values ​​for each value in the 0° image, 90° image, 180° image, and 270° image were added together, and this value was used as the total count for each value (for example, as shown in Figure 3, if the 0° image has a count of 1, the 90° image has a count of 2, the 180° image has a count of 2, and the 270° image has a count of 3, then the total count for value = 2 will be 8). 2. Each value was multiplied by the total count for each value to calculate the sum of each R value (the calculated value was called Point) (for example, as shown in Figure 3, if the total count for value = 2 is 8, the value of Point for value = 2 is 8 x 2 = 16). All total counts from 3.0 to 255 were added together (the calculated value was called Total Pixel). All points from 4.0 to 255 were added together and divided by Total Pixel to calculate the average R value.

[0129] [Calculation of standard deviation of R values] Based on the average value of the R values ​​calculated above, the standard deviation of the R values ​​of each sample was calculated. The results are shown in Table 1. 1. For each value, "value - average value of R values" was calculated (deviation). 2. Each deviation calculated in 1 was squared (deviation^2). 3. Using the deviation^2 calculated in 2, "deviation^2 x total count" was calculated for each value (point-converted deviation^2). 4. The sum of all point-converted deviation^2 was divided by the total pixel (variance). 5. The value obtained by taking the root of the variance (square root of the variance) was used as the standard deviation of the R values.

[0130] [Evaluation of the unevenness of the surface of the surface lubrication layer] The unevenness (also called the bumpy feeling) of the surface of the surface lubrication layer was evaluated for sample (1) prepared in Example 1 and comparison samples (1) and (2) prepared in Comparative Examples 1 and 2 according to the following method.

[0131] The surface of each sample was immersed in tap water for 1 minute, and then the surface was touched with a hand, and the surface roughness was evaluated sensorily according to the following evaluation criteria. The results are shown in Table 1.

[0132] (Evaluation criteria) ◯: No unevenness is felt on the surface; Δ: Some unevenness is felt on the surface; and ×: Unevenness is clearly felt on the surface.

[0133] [Sliding resistance test and durability test] The sample (1) prepared in Example 1 and the comparative samples (1) and (2) prepared in Comparative Examples 1 and 2 were evaluated for sliding resistance and durability according to the following procedures.

[0134] (Sliding resistance test) Each sample was immersed in tap water and set in a pinch tester (OAKRIVER TECHNOLOGY, DL1000), and slid 10 times at a grip force of 500 gf, a test speed of 8.3 mm / s, and a test stroke of 25 mm (grip pad material: silicone, grip pad height: 12.35 mm). Then, the sliding resistance was evaluated by measuring the measured value after 10 slides (sliding resistance value after 10 slides). Specifically, the average of the measured values ​​between 5 mm and 20 mm of the 25 mm test stroke after the 10th slide was calculated and used as the sliding resistance value (gf).

[0135] If the sliding resistance value (gf) after 10 sliding cycles was 8.5 gf or less, it was determined that the medical device had the sliding properties required, and if it was 7.5 gf or less, it was determined that the medical device had more suitable sliding properties. The results are shown in Table 1. The evaluation criteria are also shown below.

[0136] (Evaluation criteria) ◯: 7.5 gf or less; Δ: more than 7.5 gf and 8.5 gf or less; and ×: more than 8.5 gf.

[0137] (Durability Test) Each sample was immersed in tap water and placed in a pinch tester (OAKRIVER TECHNOLOGY, DL1000), and slid 50 times at a grip force of 500 gf, a test speed of 8.3 mm / s, and a test stroke of 25 mm (grip pad material: silicone, grip pad height: 12.35 mm). Next, the difference between the measured value at the 50th slide and the measured value at the 10th slide was calculated to determine the increase in sliding resistance, thereby evaluating durability. The measured value at the 10th slide was calculated using the same method as in the sliding resistance test described above. The measured value at the 50th slide was also calculated in the same way. Specifically, the average of the measured values ​​between 5 mm and 20 mm of the 25 mm test stroke at the 50th slide was calculated, and this was taken as the measured value (gf) at 50 slides. In this durability test, the smaller the difference between the measured value at the 50th slide and the measured value at the 10th slide, the better the durability was judged to be. When the result showed a negative value, it was regarded as 0 gf. The evaluation criteria are shown below, and the results are shown in Table 1.

[0138] (Evaluation criteria) ◯: Less than 5 gf; ×: 5 gf or more.

[0139]

[0140] The sample (1) prepared in Example 1 had a standard deviation of R value of 8.9, which is less than 10, while the comparative samples (1) and (2) prepared in Comparative Examples 1 and 2 had standard deviations of R value of 15.1 and 10.2, respectively, which were greater than 10. From these results, it was found that the sample (1) of Example 1 had less uneven distribution of the surface lubricant layer than the comparative samples (1) and (2) of the comparative examples, i.e., the thickness of the surface lubricant layer was less varied. Furthermore, the sample (1) of Example 1 was found to have excellent sliding properties and durability, while the comparative sample (1) of Comparative Example 1 had poor sliding properties, and the comparative sample (2) of Comparative Example 2 had poor durability. From these results, it is believed that the sample (1) of Example 1 had less uneven distribution of the surface lubricant layer, i.e., the thickness of the surface lubricant layer was less varied, resulting in excellent sliding properties and durability. On the other hand, the results of the comparative samples in the comparative examples indicate that when the surface lubricating layer is unevenly distributed and the thickness varies greatly, at least one of the sliding properties and durability is poor.

[0141] [Evaluation of Dynamic Friction Resistance Value] First, a sample (2) of Example 2 was prepared by the following method.

[0142] Example 2 Sample (2) of Example 2 was produced in the same manner as in Example 1, except that the substrate layer was a tube (outer diameter: 2.46 mm) made of polyester elastomer (Pelprene E-450B, manufactured by Toyobo MC Co., Ltd.), and the tube on which the coating film was formed (coating film-formed tube (4)) was placed in an oven, the temperature in the oven was increased to 130 ° C without stopping the temperature increase, and then stored at 130 ° C for 3 hours. Here, when the standard deviation of the R value of the surface lubricating layer of sample (2) was calculated according to the method described in the above column "Standard deviation of the R value of the surface lubricating layer", the value was 7.1.

[0143] (Measurement of Dynamic Frictional Resistance Value) Next, for Sample (2) and Comparative Sample (1) prepared in Comparative Example 1, the dynamic frictional resistance value was measured using a friction measuring instrument (Handy Tribomaster TL201, manufactured by Trinity Lab) 20 shown in FIG. 4 according to the following method, to evaluate the sliding properties and durability (sliding maintenance ability).

[0144] The sample (2) was fixed in a petri dish 12 and immersed in water 17 to a height sufficient to completely immerse the sample (2). The petri dish 12 was placed on the moving table 15 of the friction tester 20 shown in FIG. 4. A PEEK terminal (φ10 mm, R1 mm) 13 was brought into contact with the sheet, and a 100 g load 14 was applied to the terminal. The moving table 15 was moved horizontally back and forth 50 times with a sliding distance of 25 mm and a sliding speed of 16.7 mm / sec. The dynamic friction resistance (gf) was measured for each run, and the average value of the dynamic friction resistance (gf) was calculated for each run, which was defined as the dynamic friction resistance value (0°) (gf) for each run. Next, the sample (2) was rotated 180° in the circumferential direction, and the dynamic friction resistance value (180°) (gf) for each run was calculated using the same method as above. Table 2 shows the dynamic friction resistance values ​​(0°) (gf) and (180°) (gf) for sample (2) after the 5th and 50th reciprocation.

[0145] In addition, the dynamic friction resistance value (0°) (gf) and the dynamic friction resistance value (180°) (gf) were calculated for each cycle for the comparative sample (1) prepared in Comparative Example 1 using the same method as above. Table 2 shows the dynamic friction resistance value (0°) (gf) and the dynamic friction resistance value (180°) (gf) for the comparative sample (1) after the 5th and 50th cycles.

[0146]

[0147] As shown in Table 2 above, the dynamic friction resistance value (0°) and the dynamic friction resistance value (180°) of sample (2) of Example 2 were lower than those of comparative sample (1) at both the 5th and 50th times. These results indicate that Example 2 is superior to Comparative Example 1 in terms of sliding properties.

[0148] Furthermore, the dynamic friction resistance value (0°) and the dynamic friction resistance value (180°) of sample (2) of Example 2 showed small differences between the 5th and 50th times (dynamic friction resistance value (0°) was 0.3 gf, and dynamic friction resistance value (180°) was 0.53 gf). On the other hand, in comparative sample (1), the difference between the 5th and 50th times in the dynamic friction resistance value (0°) was small, but the difference between the 5th and 50th times in the dynamic friction resistance value (180°) was large (dynamic friction resistance value (0°) was 0.27 gf, and dynamic friction resistance value (180°) was 16.86 gf). These results show that sample (2) of Example 2 not only has excellent sliding properties, but also excellent durability, compared to comparative example 1.

[0149] In addition, in sample (2) of Example 2, the difference between the dynamic friction resistance value (0°) and the dynamic friction resistance value (180°) was small, at 0.13 gf at the 5th time and 0.10 gf at the 50th time. On the other hand, in comparative sample (1), the difference between the dynamic friction resistance value (0°) and the dynamic friction resistance value (180°) at the 5th time was 1.16 gf, and the difference at the 50th time was 17.75 gf, which were large. Generally, the dynamic friction resistance value of the surface lubricating layer depends on the thickness of the surface lubricating layer, and the thicker the layer, the lower the dynamic friction resistance value, and the thinner the layer, the higher the dynamic friction resistance value. In other words, a large difference between the dynamic friction resistance value (0°) and the dynamic friction resistance value (180°) indicates a large difference in the thickness of the surface lubricating layer, and a small difference between the dynamic friction resistance value (0°) and the dynamic friction resistance value (180°) indicates a small difference in the thickness of the surface lubricating layer. In this regard, the difference between the dynamic friction resistance value (0°) and the dynamic friction resistance value (180°) of sample (2) in Example 2 is small, while the difference in Comparative Example 1 is large, so it can be said that the difference in thickness of the surface lubricant layer in Example 2 is small (i.e., the thickness variation is small), and the difference in thickness of the surface lubricant layer in Comparative Example 1 is large (i.e., the thickness variation is large). These results support the evaluation results for "standard deviation of the R value of the surface lubricant layer".

[0150] This application is based on Japanese Patent Application No. 2024-129927, filed on August 6, 2024, the disclosure of which is incorporated herein by reference in its entirety.

[0151] 10 catheter, 1 base material layer, 2 surface lubrication layer, 3 lumen 12 petri dish, 13 PEEK terminal, 14 load, 15 moving table, 16 sample, 17 water.

Claims

1. A medical device comprising a base layer and a surface lubricating layer supported on at least a portion of the base layer, wherein the surface lubricating layer comprises a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, and a hydrophobic resin, and wherein the standard deviation of the R value of the surface lubricating layer stained with Congo red solution is 10 or less.

2. The medical device according to claim 1, wherein the ratio (molar ratio) of the structural unit (A) derived from the reactive monomer having an epoxy group to the structural unit (B) derived from the hydrophilic monomer in the block copolymer is 1:20 to 1:

50.

3. A medical device as described in claim 1 or 2, wherein the content (mass %) of the hydrophobic resin in the surface lubricating layer is less than the content (mass %) of the block copolymer.

4. The medical device according to claim 1 or 2, wherein the hydrophobic resin is polyvinyl chloride (PVC) resin.

5. The medical device according to claim 1 or 2, wherein the reactive monomer having an epoxy group comprises at least one member selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether.

6. The medical device according to claim 1 or 2, wherein the hydrophilic monomer comprises at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone.

7. A medical device according to claim 1 or 2, wherein the sliding resistance value of the surface lubricating layer after 10 sliding cycles in a sliding resistance test is 8.5 gf or less.

8. A method for measuring uneven distribution in a medical device having a surface lubricating layer, in which the uneven distribution of the surface lubricating layer is evaluated by the standard deviation of the R value of the surface lubricating layer stained with Congo red solution.

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