Medical instrument and medical instrument manufacturing method

Abstract

Provided is a medical instrument comprising a surface lubricating layer that exhibits excellent lubrication retention properties even in a drying process after wetting.　This medical instrument comprises a substrate layer and a surface lubricating layer supported on at least a part of the substrate layer, wherein: the surface lubricating layer contains a silicone compound and a block copolymer, which has a reactive monomer-derived constitutional unit (A) having an epoxy group and a hydrophilic monomer-derived constitutional unit (B); and when 1.0 μL of purified water is added dropwise to the surface lubricating layer, and the water contact angle 5 seconds after the water droplet of the purified water comes into contact with the surface lubricating layer is defined as θ1 and the water contact angle 5 minutes after the contact is defined as θ2, θ1 is at least 104º, and θ2 is at most 102º.

Description

Medical device and method for manufacturing medical device

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

[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 the surgeon. 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 safety and operability. 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 (corresponding to the specification of U.S. Pat. No. 5,670,558) 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, and a surface lubricating layer that is relatively difficult to peel off can be formed.

[0005] However, the present inventors have found that although the surface lubricating layer formed using the above-mentioned block copolymer exhibits excellent surface lubricity when wet with water (e.g., physiological saline solution, etc.), as the surface gradually dries over time, it becomes sticky (sticky). When stickiness develops as the surface dries, the operability of the medical device is significantly reduced. For example, the surface of a medical device such as a catheter or guidewire, particularly the area (mainly the base side) that enters and exits other devices such as introducer sheaths and catheters, dries over time during the procedure, becoming sticky as described above, and may stick to other devices. Therefore, to avoid this, it is necessary to perform an operation to maintain the wet state of the medical device surface (surface lubricating layer), for example, by spraying water (e.g., physiological saline solution, etc.) on the medical device surface or wetting the medical device surface with a water-moistened cloth.

[0006] However, such operations are a burden during the procedure, and therefore there is a demand for medical devices that can maintain high lubricity without developing stickiness even after the surface of the medical device (surface lubricating layer) becomes wet and during the drying process.

[0007] The present invention has been made in view of the above circumstances, and aims to provide a medical device having a surface lubricating layer that exhibits excellent lubrication maintenance even during the drying process after wetting. Another aim of the present invention is to provide a method for producing the above medical device.

[0008] The present inventors have conducted extensive research to solve the above problems. As a result, they have found that the above object can be achieved by forming a surface lubricating layer containing a hydrophilic block copolymer having an epoxy group and a silicone compound, and by making the water contact angle of the surface of the surface lubricating layer within a specific range, and have completed 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 as follows: 1. A medical device comprising a base layer and a surface lubricating layer carried 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 silicone compound, wherein when 1.0 μL of purified water is dropped onto the surface lubricating layer, and the water contact angle 5 seconds after the purified water droplet comes into contact with the surface lubricating layer is taken as θ1, and the water contact angle 5 minutes after the contact is taken as θ2, θ1 is 104° or more and θ2 is 102° or less; 2. In the medical device described in 1. above, when the water contact angle 1 minute after the purified water droplet comes into contact with the surface lubricating layer is taken as θ3, it is preferable that θ3 exceeds 102°; 3. The medical device described in 1. or 2. above. In the medical device described in 1., it is preferable that the surface lubricating layer contains the silicone compound and the block copolymer in a mass ratio of 0.1 to 1:1; 4. In the medical device described in any one of 1. to 3. above, it is preferable that the silicone compound contains a reactive silicone; 5. In the medical device described in 4. above, it is preferable that the reactive silicone contains a hydroxyl group (—OH), a carboxyl group, an amino group (—NH ２ ), preferably has at least one selected from the group consisting of an epoxy group, an ethylenically unsaturated group, and an alkoxysilyl group; 6. In the medical device described in any of 1. to 5. 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; 7. In the medical device described in any of 1. to 6. 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.

[0011] Other aspects of the present invention are: 8. A method for producing a medical device comprising a base layer and a surface lubricating layer carried on at least a part of the base layer, the method comprising: 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 silicone compound, and a solvent; and applying the coating liquid onto the base layer; 9. In the method for producing a medical device described in 8. above, the coating liquid preferably contains the silicone compound in an amount of 0.5 to 5 mass %; 10. In the method for producing a medical device described in 8. or 9. above, the silicone compound preferably contains a reactive silicone; 11. In the method for producing a medical device described in 10. above, the reactive silicone preferably contains a hydroxyl group (—OH), a carboxyl group, an amino group (—NH ２12. In the method for producing a medical device according to any one of items 8. to 11. above, the solvent preferably comprises at least one selected from the group consisting of methanol, ethanol, isopropyl alcohol, butanol, ethylene glycol, acetone, methyl ethyl ketone, cyclohexanone, ethyl acetate, butyl acetate, tetrahydrofuran (THF), butyl ether, dioxane, hexane, heptane, benzene, toluene, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF); 13. In the method for producing a medical device according to any one of items 8. to 12. above, the reactive monomer having an epoxy group preferably comprises at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether; 14. In the method for producing a medical device according to any one of items 8. to 13. above, the solvent preferably comprises at least one selected from the group consisting of methanol, ethanol, isopropyl alcohol, butanol, ethylene glycol, acetone, methyl ethyl ketone, cyclohexanone, ethyl acetate, butyl acetate, tetrahydrofuran (THF), butyl ether, dioxane, hexane, heptane, benzene, toluene, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF); 13. In the method for producing a medical device according to any one of items 8. to 12. above, the reactive monomer having an epoxy group preferably comprises at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether; In the method for producing a medical device described in any one of the 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.

[0012] 1 is a partial cross-sectional view schematically illustrating a surface layer structure of a representative embodiment of a medical device according to the present invention. FIG. 2 is a partial cross-sectional view schematically illustrating an example of a different surface layer structure as an application example of the embodiment of FIG. 1. FIG. 3 is a graph showing the results of a pinch test (wet-dry test) in the drying process after wetting for each sample in the examples and comparative examples. FIG. 4 is a graph showing the results of a pinch test (dry test) in a dry state (in air) for each sample in the examples and comparative examples. FIG. 5 is a graph showing the results of a pinch test (wet test) in a wet state (in water) for each sample in the examples and comparative examples. FIG. 6 is a schematic diagram showing a test apparatus for performing a sliding test on a medical device according to the present embodiment, illustrating a state in which the medical device is sandwiched between a pair of contact members. FIG. 7 is a schematic diagram showing a test apparatus for performing a sliding test on a medical device according to the present embodiment, illustrating a state in which the medical device is separated from the pair of contact members.

[0013] A medical device according to one aspect 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 silicone compound. In the medical device according to one aspect of the present invention, when 1.0 μL of purified water is dropped onto the surface lubricating layer, the water contact angle 5 seconds after the contact of the purified water droplet with the surface lubricating layer is θ1, and the water contact angle 5 minutes after the contact is θ2, θ1 is 104° or more, and θ2 is 102° or less. Hereinafter, a medical device having the above configuration will also be referred to as a "medical device according to the present invention" or a "medical device."

[0014] Herein, the structural unit (A) derived from a reactive monomer having an epoxy group is also simply referred to 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 simply referred to 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 simply referred to as the "block copolymer according to the present invention," "hydrophilic block copolymer," or "block copolymer."

[0015] In this specification, when a certain structural unit is defined as being "derived from" a certain monomer, it means that the structural unit is a structural unit that is generated by cleavage of one of the polymerizable unsaturated double bonds of the corresponding monomer.

[0016] 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.

[0017] 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" means at least one of X and Y, and includes X alone, Y alone, and a combination of X and Y.

[0018] Unless otherwise specified, the operations and measurements of physical properties are carried out under the conditions of room temperature (20 to 25°C) and relative humidity of 40 to 50% RH.

[0019] The medical device of the present invention has a surface lubricating layer comprising a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, and a silicone compound, and the water contact angle of the surface of the surface lubricating layer is within a specific range.Specifically, the medical device of the present invention has, on the surface of the surface lubricating layer, when 1.0 μL of purified water is dropped onto the surface lubricating layer, the water contact angle (θ1) of the dropped purified water droplet and the surface lubricating layer 5 seconds after contact is 104 ° or more, and the water contact angle (θ2) of the water droplet and the surface lubricating layer 5 minutes after contact is 102 ° or less.

[0020] The present inventor speculates that the occurrence of tackiness (stickiness) in the drying process after wetting is due to the hydrophilic block copolymer that gives good sliding property to surface lubrication layer.More specifically, when hydrophilic block copolymer is in a wet state, surface lubrication layer can exhibit good sliding property, but when hydrophilic block copolymer (surface lubrication layer that contains hydrophilic block copolymer) gradually dries, it can no longer exhibit the sliding property that it exhibits when wet, so it thinks that the occurrence of tackiness (stickiness) occurs.

[0021] In contrast, the medical device according to the present invention further comprises a silicone compound in the surface lubricating layer containing such a hydrophilic block copolymer. Here, the block copolymer contained in the surface lubricating layer functions as a hydrophilic component, while the silicone compound contained in the surface lubricating layer functions as a water-repellent component (hydrophobic component). The surface lubricating layer of the medical device according to the present invention contains a silicone compound, and its surface has the water contact angle θ1 (water contact angle 5 seconds after the surface lubricating layer comes into contact with a water droplet) of a specific value or more, so it can be said that it has moderate water repellency (hydrophobicity) immediately after contact with a water droplet.

[0022] It is presumed that such moderate water repellency is due to the presence of a silicone compound on the surface of the surface lubrication layer, which results in a moderately small proportion of the hydrophilic block copolymer on the surface.

[0023] Therefore, since the proportion of the hydrophilic block copolymer on the surface of the surface lubricating layer of the medical device according to the present invention is appropriately small as described above, the influence of drying of the hydrophilic block copolymer (i.e., the occurrence of stickiness) can be reduced. Therefore, according to the present invention, it is possible to provide a medical device having a surface lubricating layer that exhibits excellent lubrication maintenance even during the drying process after wetting.

[0024] Furthermore, the surface lubricating layer of the medical device according to the present invention has a water contact angle θ2 (water contact angle 5 minutes after the surface lubricating layer comes into contact with a water droplet) of a specific value or less. Such physical properties are thought to be due to the hydrophilicity of the hydrophilic block copolymer contained in the surface lubricating layer being exerted over time after the surface lubricating layer comes into contact with water (after becoming wet). Therefore, the surface lubricating layer can maintain good hydrophilicity even while containing a silicone compound, and as a result, can exhibit high lubricity (surface lubricity).

[0025] As described above, the medical device according to the present invention can achieve the desired effect of maintaining excellent lubricity (surface lubricity) while avoiding the problem of tackiness (stickiness) occurring during the drying process after wetting. Note that the above mechanism is speculation and does not limit the technical scope of the present invention.

[0026] 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 embodiments of the present invention are described with reference to the drawings, the same elements are given the same reference numerals in the description of the drawings, and duplicate explanations will be omitted.

[0027] Throughout this specification, unless otherwise specified, singular expressions should be understood to include the plural concept. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept, unless otherwise specified. Furthermore, terms used in this specification should be understood to be used in the sense commonly used in the art, unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification (including definitions) will prevail.

[0028] [Medical device] The medical device according to the present invention comprises a base layer and a surface lubricating layer supported on at least a portion of the base layer. The surface lubricating layer comprises a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, and a silicone compound. The surface lubricating layer also has the following properties: When 1.0 μL of purified water is dropped onto the surface lubricating layer, the water contact angle θ1 is 5 seconds after the purified water droplet comes into contact with the surface lubricating layer, and the water contact angle θ2 is 5 minutes after the purified water droplet comes into contact with the surface lubricating layer. The θ1 is 104° or more, and the θ2 is 102° or less.

[0029] Hereinafter, preferred embodiments of the medical device according to the present invention will be described with reference to the accompanying drawings.

[0030] Fig. 1 is a partial cross-sectional view schematically showing the surface layer structure of a representative embodiment of a medical device according to the present invention. Fig. 2 is a partial cross-sectional view schematically showing a different example of the surface layer structure as an application example of the embodiment shown in Fig. 1. Note that the reference symbols in Fig. 1 and Fig. 2 respectively represent the following: Reference symbol 1 represents the substrate layer; Reference symbol 1a represents the substrate layer core; Reference symbol 1b represents the substrate surface layer; Reference symbol 2 represents the surface lubricating layer; and Reference symbol 10 represents the medical device according to the present invention.

[0031] As shown in Figures 1 and 2, the medical device 10 of this embodiment comprises a base layer 1 and a surface lubricating layer 2 containing a block copolymer provided on at least a portion of the base layer 1 (the figures show an example in which the surface lubricating layer 2 is provided on the entire (whole) surface of the base layer 1 in the drawings). In Figures 1 and 2, the surface lubricating layer 2 is formed on both sides of the base layer 1, but the present invention is not limited to the above form, and may be any form, such as a form in which the surface lubricating layer 2 is formed on one side of the base layer 1; a form in which the surface lubricating layer 2 is formed on part of one or both sides of the base layer 1, etc.

[0032] Below, the medical device will be described in detail for each of its constituent parts.

[0033] <Substrate Layer (Substrate)> The substrate layer used in this embodiment may be made of any material, and the material is not particularly limited. Specifically, materials constituting the substrate layer 1 include metal materials, polymer materials, and ceramics.

[0034] Among the materials constituting the base layer 1, the metal material is not particularly limited, and metal materials commonly used for medical devices such as catheters, guidewires, and indwelling needles can be used. Specific examples include various stainless steels such as SUS304, SUS314, SUS316, SUS316L, SUS420J2, and SUS630, as well as gold, platinum, silver, copper, nickel, cobalt, titanium, iron, aluminum, tin, and various alloys such as nickel-titanium alloys, nickel-cobalt alloys, cobalt-chromium alloys, and zinc-tungsten alloys. These may be used alone or in combination of two or more. The metal material may be appropriately selected from those optimal for the base layer of the intended use, such as a catheter, guidewire, or indwelling needle.

[0035] Furthermore, among the materials constituting the base layer 1, 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 resin, polyolefin resin such as polyethylene resin or polypropylene resin, modified polyolefin resin, cyclic polyolefin resin, epoxy resin, polyurethane resin, diallyl phthalate resin (allyl resin), polycarbonate resin, fluororesin, amino resin (urea resin, melamine resin, benzoguanamine resin), polyester resin such as polyethylene terephthalate resin or polybutylene terephthalate resin, styrene resin, acrylic resin, polyacetal resin, vinyl acetate resin, phenolic resin, vinyl chloride resin, silicone resin (silicon resin), polyether resin, polyimide resin, etc.

[0036] Thermoplastic elastomers such as polyurethane elastomers, polyester elastomers, and polyamide elastomers (nylon elastomers) can also be used as materials for the substrate layer.

[0037] These polymeric materials may be used alone, or as a mixture of two or more kinds, or as a copolymer of two or more kinds of monomers constituting any of the above-mentioned resins or elastomers. As the polymeric material, a polymeric material that is optimal for the substrate layer of the intended use, such as a catheter, guide wire, or indwelling needle, may be appropriately selected.

[0038] The shape of the substrate layer 1 is not particularly limited, and may be appropriately selected depending on the mode of use, such as a sheet, a wire, a rod, or a tube.

[0039] Here, the entire substrate layer 1 may be made of any of the above materials. The substrate layer 1 may be a multilayer structure formed by laminating different materials in multiple layers, or a structure in which components formed of different materials are joined together for each portion of the medical device. Alternatively, as shown in FIG. 2, the substrate may have a structure in which the surface of a substrate layer core portion 1a formed of any of the above materials is coated with any of the other materials by an appropriate method to form a substrate surface layer 1b. Examples of the latter case include a substrate in which the surface of a substrate layer core portion 1a formed of a resin material or the like is coated with a metal material by an appropriate method (conventionally known methods such as plating, metal vapor deposition, sputtering, etc.) to form a substrate surface layer 1b; a substrate in which the surface of a substrate layer core portion 1a formed of a hard reinforcing material such as a metal material or a ceramic material is coated with a polymer material that is softer than the metal reinforcing material by an appropriate method (conventionally known methods such as dipping, spraying, coating / printing, etc.); or a substrate in which the reinforcing material forming the substrate layer core portion 1a and the polymer material are combined to form a substrate surface layer 1b. The base layer core 1a may be a multilayer structure formed by laminating multiple layers of different materials, or a structure in which different parts of the medical device are joined together. A separate middle layer (not shown) may be formed between the base layer core 1a and the base surface layer 1b. The base surface layer 1b may also be a multilayer structure formed by laminating multiple layers of different materials, or a structure in which different parts of the medical device are joined together.

[0040] <Surface lubricating layer (coating layer)> The surface lubricating layer is supported on at least a part of the substrate layer 1. Here, the reason why the surface lubricating layer 2 is supported on at least a part of the surface of the substrate layer 1 is that in medical devices such as catheters, guide wires, and indwelling needles, which are used for this purpose, it is not necessary for all surfaces (the entire surface) of these medical devices to have lubricity when wet, and the surface lubricating layer only needs to be supported on the surface portion (sometimes a part or sometimes all) that is required to have lubricity when wet.For this reason, as described above, the surface lubricating layer includes the form formed to cover both sides of the substrate layer as shown in Figure 1 and Figure 2; the form formed to cover only one side of the substrate layer; the form formed to cover parts of both sides of the substrate layer in the same or different forms; the form formed to cover part of one side of the substrate layer, etc.

[0041] (Water contact angles θ1, θ2 and θ3) When 1.0 μL of purified water is dropped onto the surface lubricating layer, the water contact angle (θ1) is 104 ° or more 5 seconds after the dropped water droplet and the surface lubricating layer contact (5 seconds have passed).In addition, when 1.0 μL of purified water is dropped onto the surface lubricating layer as described above, the water contact angle (θ2) is 102 ° or less 5 minutes after the dropped water droplet and the surface lubricating layer contact (5 minutes have passed).Furthermore, when 1.0 μL of purified water is dropped onto the surface lubricating layer as described above, the water contact angle (θ3) is preferably more than 102 ° 1 minute after the dropped water droplet and the surface lubricating layer contact (1 minute have passed). In this specification, the measurement of water contact angle θ1, θ2 and the water contact angle θ3 described later shall be carried out under the conditions of room temperature (25 ℃) and relative humidity 50%RH, and the specific measurement method is the method described in Example.In addition, in this specification, when 1.0 μL of purified water is dropped onto the surface lubrication layer, the water contact angle after 5 seconds (after 5 seconds) from the contact of the dropped water droplet with the surface lubrication layer, the water contact angle after 5 minutes (after 5 minutes) and the water contact angle after 1 minute (after 1 minute) are also simply referred to as "water contact angle θ1", "water contact angle θ2" and "water contact angle θ3", respectively.

[0042] From the viewpoint of effectively suppressing tackiness (stickiness) during the drying process after wetting, the water contact angle θ1 is preferably 105° or more, more preferably 110° or more, even more preferably 115° or more, and particularly preferably 120° or more. In addition, although there is no particular upper limit for the water contact angle θ1, from the viewpoint of maintaining good slidability (surface lubricity) when wet, it is preferably 140° or less, and more preferably 130° or less.

[0043] Therefore, in one embodiment of the present invention, the water contact angle θ1 is preferably 104 to 140°, more preferably 105 to 140°, even more preferably 110 to 140°, particularly preferably 115 to 130°, and most preferably 120 to 130°.

[0044] Furthermore, from the viewpoint of obtaining excellent sliding properties (surface lubricity) when wet, the water contact angle θ2 is preferably 101° or less, and more preferably 100° or less. Furthermore, the lower limit of the water contact angle θ2 is not particularly limited, but from the viewpoint of effectively suppressing tackiness (stickiness) during the drying process after wetting, it is preferably 78° or more, more preferably 80° or more, even more preferably 85° or more, and particularly preferably 90° or more.

[0045] Therefore, in one embodiment of the present invention, the water contact angle θ2 is preferably 78 to 102°, more preferably 80 to 102°, even more preferably 85 to 102°, still more preferably 85 to 101°, and particularly preferably 90 to 100°. Furthermore, when the water contact angle θ2 is in any of these ranges, it is preferable that the water contact angle θ1 is within any of the above-mentioned preferred ranges.

[0046] Furthermore, from the viewpoint of effectively suppressing tackiness (stickiness) during the drying process after wetting, the water contact angle θ3 is more preferably 103° or more, even more preferably 105° or more, and particularly preferably 110° or more. Furthermore, although there is no particular upper limit for the water contact angle θ3, from the viewpoint of maintaining good slidability (surface lubricity) when wet, it is preferably 130° or less, more preferably 125° or less, and particularly preferably 120° or less.

[0047] Therefore, in one embodiment of the present invention, the water contact angle θ3 is preferably 102 to 130°, more preferably greater than 102° and equal to or less than 130°, even more preferably 103 to 130°, still more preferably 105 to 125°, and particularly preferably 110 to 120°.

[0048] Furthermore, in another embodiment, the surface lubricating layer may have a water contact angle θ2 of 78 to 102° and a water contact angle θ3 of 102 to 130°. In another preferred embodiment, the surface lubricating layer may have a water contact angle θ2 of 78 to 102° and a water contact angle θ3 of greater than 102° and not greater than 130°. In another preferred embodiment, the surface lubricating layer may have a water contact angle θ2 of 80 to 102° and a water contact angle θ3 of 103 to 130°. In another preferred embodiment, the surface lubricating layer may have a water contact angle θ2 of 85 to 101° and a water contact angle θ3 of 105 to 125°. In another preferred embodiment, the surface lubricating layer may have a water contact angle θ2 of 90 to 100° and a water contact angle θ3 of 110 to 120°.

[0049] The water contact angle θ1, θ2 and θ3 of surface lubrication layer can be appropriately controlled by the content ratio (mass ratio) of block copolymer and silicone compound contained in surface lubrication layer, and the heating and drying conditions after coating the coating liquid containing these components on the base layer.The content ratio (mass ratio) of each component that constitutes surface lubrication layer and the heating and drying conditions etc. will be described later in detail.

[0050] (Block copolymer) In the present invention, the block copolymer forms a surface lubricating layer supported on at least a part of the base layer. That is, in the medical device of the present invention, the surface lubricating layer comprises a block copolymer. Note that "supported" means that the surface lubricating layer is fixed in a state that it is not easily separated from the surface of the base layer, and includes not only the form in which the entire surface of the base layer is completely covered with the surface lubricating layer, but also the form in which only a part of the surface of the base layer is covered with the surface lubricating layer, that is, the form in which the surface lubricating layer is attached to only a part of the surface of the base layer.

[0051] 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.

[0052] 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 can also occur due to the open epoxy group.

[0053] 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.

[0054] Among these, 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. That is, 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. Furthermore, in a particularly preferred embodiment of the present invention, the reactive monomer having an epoxy group is glycidyl methacrylate.

[0055] The reactive monomers may be used alone or in combination of two or more. That is, the structural unit (A) 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 structural unit (A) may be in the form of a block copolymer or a random copolymer.

[0056] The hydrophilic monomers constituting the block copolymers swell when in contact with body fluids or aqueous solvents, thereby imparting lubricity (surface lubricity) to medical devices. Therefore, by introducing the structural unit (B) derived from such a hydrophilic monomer into the block copolymer, the lubricity (surface lubricity) 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.

[0057] 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, diethylene glycol mono(meth)acrylate, 1,6-hexanediol mono(meth)acrylate, pentaerythritol tri(meth)acrylate, dipentaerythritol penta(meth)acrylate, neopentyl glycol mono(meth)acrylate, trimethylolpropane di(meth)acrylate, trimethylolethane di(meth)acrylate, 2-hydroxy-3-phenyloxypropyl(meth)acrylate, 4-hydroxycyclohexyl(meth)acrylate, 2-hydroxy-3-phenyloxy(meth)acrylate, 4-hydroxycyclohexyl(meth)acrylate, cyclohexanedimethanol mono(meth)acrylate, poly(ethylene glycol) methyl ether acrylate, and poly(ethylene glycol) methyl ether methacrylate.From the viewpoints of imparting excellent lubricity, 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.

[0058] Among these, in consideration of the imparting of excellent lubricity, ease of synthesis, and operability, N,N-dimethylacrylamide, acrylamide, or 2-hydroxyethyl methacrylate are more preferred, and N,N-dimethylacrylamide is particularly preferred. That is, 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. Furthermore, in a particularly preferred embodiment of the present invention, the hydrophilic monomer is N,N-dimethylacrylamide.

[0059] The hydrophilic monomers may be used alone or in combination of two or more. That is, the structural unit (B) 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 hydrophilic monomers. When two or more types are used, the structural unit (B) may be in the form of a block copolymer or a random copolymer.

[0060] The block copolymer has a structural unit (A) derived from the reactive monomer and a structural unit (B) derived from the hydrophilic monomer. 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, lubrication maintenance, coating layer strength, and bonding with the substrate layer, the ratio of the structural unit (A) to the structural unit (B) (molar ratio of structural unit (A):structural unit (B)) is preferably 1:2 to 1:100, more preferably 1:2 to 1:50, even more preferably 1:5 to 1:50, and particularly preferably 1:10 to 1:30. Within this range, the surface lubricating layer can exhibit sufficient lubricity due to the structural unit (B), and can exhibit sufficient coating layer strength, bonding with the substrate layer, 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 feed ratio (molar ratio) of each monomer during the production stage of the block copolymer. Therefore, the charging ratio (molar ratio) of the reactive monomer having an epoxy group to the hydrophilic monomer in the production stage of the block copolymer is preferably 1:2 to 1:100, more preferably 1:2 to 1:50, even more preferably 1:5 to 1:50, and particularly preferably 1:10 to 1:30. 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).

[0061] 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.

[0062] 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 the total 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) (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 (surface lubricity) 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%).

[0063] 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.

[0064] In one embodiment of the present invention, the block copolymer according to the present invention is essentially composed of a structural unit (A) derived from at least one reactive monomer selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether, and a structural unit (B) derived from at least one hydrophilic monomer selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone, or is composed only of the structural unit (A) and the structural unit (B).

[0065] In one embodiment of the present invention, the block copolymer according to the present invention is essentially composed 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, or is composed only of the structural unit (A) and the structural unit (B).

[0066] In one embodiment of the present invention, the block copolymer according to the present invention is essentially composed of a structural unit (A) derived from glycidyl methacrylate (a reactive monomer having an epoxy group) and a structural unit (B) derived from N,N-dimethylacrylamide (a hydrophilic monomer), or is composed only of the structural unit (A) and the structural unit (B).

[0067] 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.

[0068] The method for producing the block copolymer is not particularly limited, and can be prepared by applying conventional polymerization methods such as living radical polymerization, polymerization using a macroinitiator, and polycondensation. Among 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 include methods described in JP-A-11-263819, JP-A-2002-145971, JP-A-2006-316169, and the like, as well as atom transfer radical polymerization (ATRP), which can be applied in the same manner or with appropriate modifications. Furthermore, in polymerization 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 can be prepared, followed by polymerizing the macroinitiator with a monomer for forming the hydrophilic moiety, thereby preparing a block copolymer having a hydrophilic moiety and a reactive moiety.

[0069] After polymerization, the block copolymer is preferably purified by a common purification method such as reprecipitation, dialysis, ultrafiltration, or extraction.

[0070] (Silicone Compound) The silicone compound contained in the surface lubricating layer is not particularly limited, and may be a reactive silicone, a non-reactive silicone, or a combination of these.

[0071] From the viewpoint of forming a uniform coating without phase separation with the block copolymer constituting the surface lubrication layer and obtaining stable sliding properties (surface lubricity), it is preferable that the silicone compound contains a reactive silicone. In this way, by forming a uniform coating, it is easier to suppress adhesion (stickiness) during the drying process after wetting. In addition, by containing a reactive silicone together with the block copolymer, they can form a network through a crosslinking reaction. As a result, it is presumed that the mobility of the block copolymer can be reduced, and adhesion (stickiness) during the drying process after wetting can be more easily suppressed. Furthermore, the network of the block copolymer and the reactive silicone formed by the crosslinking reaction is more likely to swell when wet, thereby obtaining excellent surface lubricity, and such excellent surface lubricity can be obtained for a long period of time.

[0072] Here, the term "reactive silicone" refers to a silicone compound having a reactive group that can react with a reactive functional group contained in the block copolymer, such as an epoxy group (which may also be a glycidyl group).

[0073] Therefore, in this specification, "the surface lubricating layer comprises reactive silicone (as silicone compound)" not only includes the form of containing unreacted reactive silicone, but also includes the form of containing the reaction product of reactive silicone and block copolymer in addition to reactive silicone.Furthermore, "the surface lubricating layer comprises reactive silicone and block copolymer (as silicone compound)" not only includes the form of containing unreacted reactive silicone and unreacted block copolymer, but also includes the form of containing the reaction product of reactive silicone and block copolymer.Here, the reaction rate of reactive silicone and block copolymer does not have to be 100%.In other words, the surface lubricating layer may further contain at least one of unreacted reactive silicone and unreacted block copolymer in addition to the above-mentioned reaction product (reaction product).

[0074] The reactive group of the reactive silicone is not particularly limited, but examples thereof include a hydroxyl group (—OH), a carboxyl group, an amino group (—NH ２), epoxy groups, ethylenically unsaturated groups, and alkoxysilyl groups. Therefore, in one embodiment, the reactive silicone preferably has at least one selected from the group consisting of a hydroxyl group (—OH), a carboxyl group, an amino group, an epoxy group, an ethylenically unsaturated group, and an alkoxysilyl group. More preferably, the reactive silicone has at least one selected from the group consisting of a hydroxyl group, a carboxyl group, an amino group, and an epoxy group. Particularly preferably, the reactive silicone has an amino group and / or an epoxy group. The epoxy group may be contained in the form of a glycidyl group.

[0075] The reactive silicone is not particularly limited as long as it is a silicone having the above-mentioned reactive group, and examples thereof include amino-modified silicone, epoxy-modified silicone, carboxy-modified silicone, (meth)acrylic-modified ((meth)acryloyl-modified) silicone, carbinol-modified silicone, silanol-modified silicone, etc. Among these, amino-modified silicone and / or epoxy-modified silicone are preferred as the reactive silicone because of their excellent reactivity with the epoxy group contained in the block copolymer. The above-mentioned reactive silicones can be used alone or in combination of two or more. When two or more types are used, the content of the reactive silicones represents the total amount thereof.

[0076] In one embodiment, the silicone compound constituting the surface lubricating layer can be a reactive silicone. That is, the silicone compound contained in the surface lubricating layer may be substantially composed of only reactive silicone. Here, "the silicone compound contained in the surface lubricating layer is substantially composed of only reactive silicone" refers to a form in which the surface lubricating layer does not intentionally contain silicone compounds other than reactive silicone (i.e., non-reactive silicone), at least intentionally. Therefore, the surface lubricating layer that inevitably contains a trace amount of silicone compounds other than reactive silicone due to raw materials, manufacturing methods, etc. is included in the above form. In other words, the above form refers to a form in which the silicone compound contained in the surface lubricating layer does not contain silicone compounds other than reactive silicone.

[0077] In a preferred embodiment, the silicone compound constituting the surface lubrication layer further contains a non-reactive silicone in addition to the reactive silicone. That is, it is preferable that the silicone compound contained in the surface lubrication layer contains a reactive silicone and a non-reactive silicone. According to such an embodiment, it is easier to obtain the effect of suppressing stickiness (stickiness) during the drying process after wetting, and also has excellent sliding properties in a wet state. Here, "non-reactive silicone" refers to a silicone compound that does not have a reactive group.

[0078] The non-reactive silicone is not particularly limited as long as it is a silicone that does not have the above-mentioned reactive group, and examples thereof include dimethyl silicone, methylphenyl silicone, methylhydrogen silicone, etc. Among them, dimethyl silicone is preferred as the non-reactive silicone. The non-reactive silicone can be used alone or in combination of two or more. When two or more types are used, the content of the non-reactive silicone represents the total amount thereof.

[0079] The silicone compound may be a commercially available product or a synthetic product. Commercially available reactive silicone products include KF-393, KF-859, KF-860, KF-864, KF-865, KF-868, KF-880, KF-8002, KF-8004, KF-8005, KF-8008, KF-8012, X-22-343, KF-101, KF-1001, X-22-2000, X-22-4039, X-22-4015, X-22-3701E, X-22-4741, KF-1002, X-22-163, and X-22-164 (manufactured by Shin-Etsu Chemical Co., Ltd.). Commercially available non-reactive silicone products that can be used include SH-200, SH510, SH550, and SH710 (manufactured by Dow Corning Toray Co., Ltd.), and KF-96, KF-96H, KF-965, KF-968, KF-50, KF-53, and KF-54 (manufactured by Shin-Etsu Chemical Co., Ltd.).

[0080] As for the synthesis method, known methods for synthesizing silicone compounds can be used as is or with appropriate modifications. Examples of methods for synthesizing reactive silicones include a method of reacting an amino group-containing silane with a silanol group-containing polydiorganosiloxane, and a method of reacting an epoxy group-containing silane with a silanol group-containing polydiorganosiloxane. The reaction between these reactive group-containing silane compounds and silanol group-containing polydiorganosiloxanes may be carried out by stirring and heating these compounds, using a solvent as needed. It is preferable to carry out the reaction so that the amino group-containing silane / epoxy group-containing silane ratio is 1 to 5 mass %, and the silanol group-containing polydiorganosiloxane ratio is 95 to 99 mass % (total 100 mass %).

[0081] Examples of the amino group-containing silane include γ-aminopropyltrimethoxysilane, γ-aminopropylmethyldimethoxysilane, γ-aminopropyltriethoxysilane, γ-aminopropylmethyldiethoxysilane, N-(β-aminoethyl)aminomethyltrimethoxysilane, γ-(β-aminoethyl)aminopropyltrimethoxysilane, γ-(N-(β-aminoethyl)amino)propylmethyldimethoxysilane, N-(β-aminoethyl)aminomethyltributoxysilane, and γ-(N-(β-(N-(β-aminoethyl)amino)ethyl)amino)propyltrimethoxysilane.

[0082] Examples of the epoxy group-containing silane include γ-glycidoxypropyltrimethoxysilane, γ-glycidoxypropylmethyldimethoxysilane, β-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, β-(3,4-epoxycyclohexyl)ethylmethyldimethoxysilane, β-(3,4-epoxycyclohexyl)ethyltriethoxysilane, and β-(3,4-epoxycyclohexyl)ethylmethyldiethoxysilane.

[0083] The organic group bonded to the silicon atom of the silanol group contained in the polydiorganosiloxane containing the silanol group can be an alkyl group such as a methyl group, a phenyl group, a vinyl group, etc. From the viewpoint of ease of synthesis of the polydiorganosiloxane, the organic group is preferably a methyl group or a phenyl group, more preferably a methyl group. Specific examples of the polydiorganosiloxane containing the silanol group include polydimethylsiloxane in which one end is blocked with a silanol group and the other end is blocked with a trimethylsilyl group, polydimethylsiloxane in which both ends are blocked with silanol groups, and polymethylphenylsiloxane in which both ends are blocked with silanol groups.

[0084] The content of the silicone compound in the surface lubricating layer is not particularly limited as long as it is an amount that satisfies the ranges of the water contact angles θ1 and θ2 (preferably, also the water contact angle θ3).

[0085] The mass ratio of the silicone compound to the block copolymer in the surface lubricating layer (silicone compound:block copolymer) is preferably 0.1 to 1:1. That is, the surface lubricating layer preferably contains the silicone compound and the block copolymer in a mass ratio (silicone compound:block copolymer) of 0.1 to 1:1. Furthermore, the mass ratio of the silicone compound to the block copolymer in the surface lubricating layer is more preferably greater than 0.1 and less than 1:1, and particularly preferably greater than 0.1 and 0.8 or less:1. By setting the mass ratio of the silicone compound to the block copolymer in the surface lubricating layer within the above range, it becomes easy to control the water contact angles θ1 and θ2 of the surface lubricating layer within a predetermined range. Furthermore, the water contact angle θ3 can be set within the above preferred range. Furthermore, since the proportion of the block copolymer exposed on the surface of the surface lubricating layer can be appropriately reduced, it is easier to suppress the occurrence of stickiness (stickiness) due to the block copolymer during the drying process.

[0086] In this specification, the "content of silicone compound" refers to the total amount of non-reactive silicone in addition to reactive silicone when the silicone compound contains both reactive silicone and non-reactive silicone. Furthermore, the "content of silicone compound" refers to the total mass of the silicone compound component (the total mass of the unreacted portion and the portion reacted with the block copolymer). In this specification, the content of reactive silicone refers to the total mass of the unreacted portion and the portion reacted with the block copolymer.

[0087] When the surface lubricating layer contains a reactive silicone as the silicone compound, the mass ratio of the reactive silicone to the block copolymer is not particularly limited, but the mass ratio of the reactive silicone to the block copolymer in the surface lubricating layer (reactive silicone:block copolymer) is preferably 0.01 to 1:1, more preferably 0.03 to 0.9:1, and particularly preferably 0.04 to 0.8:1. By using the above mass ratio, phase separation with the block copolymer can be more effectively suppressed, making it easier to form a uniform coating. In addition, while sufficiently ensuring the lubricity (slidability) of the surface lubricating layer, the crosslinking of the block copolymer is sufficiently promoted without excessively progressing (crosslinking can be moderately promoted). Therefore, the lubricity and durability of the obtained surface lubricating layer can be fully exhibited.

[0088] When the surface lubricating layer contains reactive silicone and non-reactive silicone as silicone compounds, the mass ratio thereof is not particularly limited, but the mass ratio of reactive silicone to non-reactive silicone in the surface lubricating layer (reactive silicone: non-reactive silicone) is preferably 0.01 to 1:1, more preferably 0.03 to 1:1, even more preferably 0.05 to 1:1, even more preferably 0.1 to 1:1, particularly preferably 0.5 to 0.8:1, and most preferably 0.6 to 0.7:1. By setting the mass ratio above, phase separation with the block copolymer can be more effectively suppressed, making it easier to form a uniform coating. In addition, while sufficiently ensuring the lubricity (slidability) of the surface lubricating layer, the crosslinking of the block copolymer is sufficiently promoted without excessively progressing (crosslinking can be moderately promoted). Therefore, the lubricity and durability of the obtained surface lubricating layer can be fully exhibited.

[0089] (Other Components) The surface lubricating layer may contain other components in addition to the block copolymer and the silicone compound. The other components are not particularly limited and are selected appropriately depending on, for example, the application of the medical device.

[0090] (Average tension (sliding resistance value)) From the viewpoint of obtaining excellent surface lubricity and suppressing tackiness (stickiness) during the drying process after wetting, the surface lubricating layer of the medical device according to the present invention preferably has an average tension of less than 550 gf when slid 40 times during the drying process after wetting, more preferably less than 500 gf, even more preferably less than 400 gf, and particularly preferably less than 300 gf. On the other hand, the lower limit is not particularly limited, but is about 100 gf. The specific method for measuring the average tension is the method described in the section [Evaluation of sliding resistance during the drying process after wetting] in the Examples.

[0091] Furthermore, from the viewpoint of improving the operability during the procedure, the surface lubricating layer of the medical device according to the present invention preferably has an average tension of 200 gf or less, more preferably 150 gf or less, even more preferably less than 100 gf, particularly preferably less than 50 gf, and most preferably 40 gf or less when wet.On the other hand, the lower limit is not particularly limited, but is about 10 gf.In addition, the specific method for measuring the average tension is the method described in the section [Evaluation of sliding resistance in wet state] in the examples.

[0092] [Method for manufacturing medical device] The surface lubricating layer of the above medical device may be formed using any method as long as it is possible to form a coating film containing a block copolymer and a silicone compound on a base layer, but it is preferably formed by applying a coating liquid containing a block copolymer, a silicone compound, and a solvent onto the base layer.

[0093] Therefore, another aspect of the present invention provides a method for producing a medical device comprising a base layer and a surface lubricating layer carried on at least a portion of the base layer, the method comprising: 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 silicone compound, and a solvent; and applying the coating liquid to the base layer. Hereinafter, the method for producing a medical device having the above-mentioned configuration will also be referred to as the "production method according to the present invention" or "production method".

[0094] The method for producing a medical device according to the present invention includes 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 silicone compound, and a solvent ((I) preparation step); and applying the coating liquid onto a substrate layer ((II) application step). In this way, by using a solution containing a silicone compound together with the block copolymer as the coating liquid, a medical device having a surface lubricating layer that exhibits excellent lubrication retention even during the drying process after wetting can be obtained.

[0095] The medical device manufactured by the method of the present invention has a structure in which a surface lubricating layer is supported on a substrate layer by applying a coating liquid containing a block copolymer and a silicone compound that form the surface lubricating layer to the substrate layer. In the coating liquid, the block copolymer and the silicone compound are dissolved in a solvent (the block copolymer and the silicone compound are uniformly mixed in the coating liquid). Therefore, the block copolymer and the silicone compound can form a uniform surface lubricating layer without forming a phase-separated structure.

[0096] Therefore, the surface lubricating layer of the medical device manufactured by the above manufacturing method can easily control the water contact angle θ1 to 104° or more and the water contact angle θ2 to 102° or less. It also becomes easier to achieve a water contact angle θ3 exceeding 102°. Furthermore, according to the above manufacturing method, it becomes easier to control the water contact angles θ1, θ2, and θ3 described in the above [Medical Device] section within preferred ranges.

[0097] In the method for producing a medical device according to the present invention, the terms water contact angles θ1, θ2, and θ3, block copolymer, silicone compound, etc. are the same as those described in the above section [Medical Device], and therefore will not be explained here.

[0098] In the method for producing a medical device according to the present invention, further steps such as a drying and / or heat treatment step ((III) drying / heat treatment step) and a washing step ((IV) washing step) may be carried out after the step (II), as necessary. Of these, it is preferable to carry out at least the drying / heat treatment step (III) after the step (II). Each of the steps (I) to (IV) will be described below.

[0099] (I) Preparation Step In this step, a coating liquid containing a block copolymer, a silicone compound, and a solvent is prepared. Here, in this step, the coating liquid may be prepared by mixing the block copolymer, the silicone compound, and the solvent to prepare the coating liquid. Alternatively, a coating liquid containing a block copolymer, a silicone compound, and a solvent may be purchased and used.

[0100] A preferred embodiment of preparing a coating liquid by mixing a block copolymer, a silicone compound, and a solvent will be described in detail below.

[0101] (Preparation of Coating Liquid) A coating liquid is prepared using the block copolymer, silicone compound, and solvent. The order and method of adding the block copolymer, silicone compound, and solvent are not particularly limited. The components may be added all at once or separately, stepwise, or continuously.

[0102] The method for mixing the components is not particularly limited, and any known method can be used. Methods for preparing the coating liquid include a method in which the silicone compound and the block copolymer are added sequentially to a solvent, a method in which the block copolymer and the silicone compound are added sequentially to a solvent, and a method in which the silicone compound and the block copolymer are added all at once to a solvent.

[0103] From the viewpoint of easily preparing a uniform solution (coating liquid), it is preferable to sequentially add the silicone compound and the block copolymer to the solvent. This addition may be performed while stirring, if necessary. More specifically, it is preferable to mix the solvent with the silicone compound (preferably the silicone compound) to obtain a solution of the silicone compound, and then further mix the block copolymer. By adopting such a form, it becomes more difficult for a phase separation structure between the block copolymer and the silicone compound to form, and a more uniform surface lubrication layer can be formed. As a result, the occurrence of tackiness (stickiness) during the drying process after wetting can be more effectively suppressed.

[0104] The solvent used to prepare the coating liquid is not particularly limited as long as it can dissolve the block copolymer and silicone compound (and other components, if used), and is appropriately selected depending on the type of block copolymer and silicone compound (and other components, if used). Specific examples of solvents for the coating liquid include alcohol-based solvents such as methanol, ethanol, isopropyl alcohol, butanol, and ethylene glycol; ketone-based solvents such as acetone, methyl ethyl ketone, and cyclohexanone; ester-based solvents such as ethyl acetate and butyl acetate; ether-based solvents such as tetrahydrofuran (THF), butyl ether, and dioxane; aliphatic hydrocarbon-based solvents such as hexane and heptane; aromatic hydrocarbon-based solvents such as benzene and toluene; dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and the like. These solvents may be used alone or in combination (in the form of a mixed solvent) of two or more types.

[0105] Among these, from the viewpoint of excellent solubility of the block copolymer and the silicone compound (particularly, reactive silicone), the solvent preferably contains at least one selected from the group consisting of methanol, ethanol, isopropyl alcohol, butanol, ethylene glycol; acetone, methyl ethyl ketone, cyclohexanone; ethyl acetate, butyl acetate; tetrahydrofuran (THF), butyl ether, dioxane; hexane, heptane; benzene, toluene; dimethyl sulfoxide (DMSO); and N,N-dimethylformamide (DMF), more preferably contains at least one selected from the group consisting of acetone, methyl ethyl ketone, cyclohexanone; tetrahydrofuran, butyl ether, and dioxane, even more preferably contains acetone and / or tetrahydrofuran, and particularly preferably contains tetrahydrofuran.

[0106] The concentration of the block copolymer in the coating solution is not particularly limited. From the viewpoint of further improving the coatability and the lubricity and durability of the surface lubrication 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, and particularly preferably 3 to 10% by mass. If the concentration of the block copolymer is within the above range, the lubricity and durability of the resulting surface lubrication layer can be fully exhibited. Furthermore, a uniform surface lubrication 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.

[0107] The concentration of the silicone compound in the coating liquid is not particularly limited as long as it satisfies the ranges of the water contact angles θ1 and θ2 (preferably, also the water contact angle θ3). From this perspective, the concentration of the silicone compound in the coating liquid is preferably 0.01 to 15% by mass, more preferably 0.1 to 10% by mass, even more preferably 0.5 to 5% by mass, and particularly preferably 0.5% by mass or more and less than 5% by mass. If the concentration of the silicone compound is within the above range, it is possible to effectively suppress tackiness (stickiness) during the drying process after wetting. However, even if the concentration is outside the above range, it is sufficiently usable as long as it does not affect the effects of the present invention.

[0108] Furthermore, the preferred mixing ratio (mass ratio) of the block copolymer and the silicone compound in the coating liquid is the same as the preferred content ratio (mass ratio) of the block copolymer and the silicone compound present in the surface lubrication layer.If the mass ratio of the block copolymer and the silicone compound in the coating liquid is within the above range, it is easy to control the water contact angles θ1 and θ2 of the surface lubrication layer within a predetermined range.In addition, the water contact angle θ3 can be set within the above preferred range.Furthermore, the durability and lubricity of the surface lubrication layer can be fully exhibited.In addition, when a reactive silicone is used as the silicone compound, the preferred mixing ratio (mass ratio) of the reactive silicone and the block copolymer in the coating liquid is the same as the preferred mass ratio of the reactive silicone and the block copolymer in the surface lubrication layer.

[0109] In addition, when using reactive silicone and non-reactive silicone as silicone compound, the preferred mixing ratio (mass ratio) of reactive silicone and non-reactive silicone in coating liquid is the same as the preferred mass ratio of reactive silicone and non-reactive silicone in surface lubrication layer.If the mass ratio of reactive silicone and non-reactive silicone in coating liquid is within the above-mentioned range, the lubricity (slidability) of surface lubrication layer can be fully ensured, while the crosslinking of block copolymer can be fully advanced without being excessively advanced (can be moderately promoted crosslinking).Therefore, the lubricity and durability of the surface lubrication layer obtained can be fully exhibited.

[0110] (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.

[0111] The substrate layer may be made of any material, such as metal materials, polymer materials, ceramics, etc. Specific examples of these materials are the same as those described above in the section <Substrate Layer (Substrate)>, so detailed description will be omitted here.

[0112] The method for applying (coating) the coating liquid to the surface of 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.

[0113] 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.

[0114] 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.

[0115] When it is difficult to immerse only a portion of the substrate layer in the coating liquid, the surface portion of the substrate layer that does not need to form a surface lubricating layer can be protected (coated, etc.) with a suitable removable (attachable) member or material, and then the substrate layer can be immersed in the coating liquid to coat the substrate layer with the coating liquid. After that, the protective member (material) on the surface portion of the substrate layer that does not need to form a surface lubricating layer can be removed, and then the substrate layer can be reacted by heat treatment or the like to form a surface lubricating layer on the desired surface portion of the substrate layer. However, the present invention is not limited to these formation methods, and a surface lubricating layer can be formed using any conventionally known method. For example, when it is difficult to immerse only a portion of the substrate layer in the coating liquid, other coating methods (e.g., a method of applying the coating liquid to a predetermined surface portion of a medical device using an application device such as a sprayer, bar coater, die coater, reverse coater, comma coater, gravure coater, spray coater, or doctor knife) can be used instead of the immersion method. 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.

[0116] The amount of coating liquid applied is preferably such that the thickness (dry film thickness) of the resulting coating (surface lubricating layer) is 0.1 to 10 μm, more preferably 0.3 to 5 μm, and even more preferably 0.5 to 3 μm. If the amount of coating 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 of coating 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.

[0117] (III) Drying / heat treatment step In the manufacturing method of the medical device according to the present invention, if necessary, it is preferable to carry out a heat treatment step after applying a coating liquid to the substrate layer in the above (II) coating step to form a coating film (coating layer). By carrying out the heat treatment step, not only can the solvent be easily removed, but also a stronger surface lubrication layer can be formed. In addition, it is easier to control the water contact angles θ1 and θ2 (and further, the water contact angle θ3).

[0118] The conditions for the heat treatment are not particularly limited, as long as they are conditions that allow the formation of a surface lubrication layer on the substrate layer that contains a block copolymer and a silicone compound and that satisfies the ranges of the water contact angles θ1 and θ2 (preferably, also the water contact angle θ3).

[0119] The temperature of the heat treatment is not particularly limited, but is preferably 50 to 200°C, more preferably 100 to 180°C. By maintaining (heat treating) at such a temperature, it becomes easy to control the water contact angles θ1 and θ2 (and further the water contact angle θ3) of the surface lubricating layer formed within a predetermined range. Furthermore, by maintaining the temperature at the above, a strong coating layer (surface lubricating layer) is formed. The temperature may be changed during the heat treatment.

[0120] The heat treatment time is not particularly limited, but is preferably 15 minutes to 20 hours, more preferably 30 minutes to 12 hours. By setting such a time, it becomes easy to control the water contact angles θ1 and θ2 (and further the water contact angle θ3) of the formed surface lubricating layer within a predetermined range. Furthermore, the crosslinking reaction in the block copolymer is effectively promoted, and a strong coating layer (surface lubricating layer) is formed, so that high lubricity (surface lubricity) can be maintained for a longer period of time.

[0121] A drying step may be carried out before the heat treatment step. In the drying step, the solvent is removed to a certain extent, 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 carried out under normal pressure (atmospheric pressure), or under increased or reduced pressure.

[0122] As the means (apparatus) for carrying out the heat treatment step and drying step, for example, an oven, a reduced pressure dryer, etc. can be used, but in the case of natural drying, no particular drying means (apparatus) is required.

[0123] <Uses of Medical Device> Examples of the medical device according to the present invention include devices that are used in contact with body fluids, blood, etc., and the device has a surface that is lubricious in body fluids, aqueous liquids such as physiological saline, and is capable of improving operability and reducing damage to tissue mucosa. Specific examples of the medical device according to the present invention include, but are not limited to, catheters, guide wires, indwelling needles, etc. that are used in blood vessels.

[0124] 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.

[0125] Synthesis Example 1 The following reaction was carried out to produce a block copolymer (1).

[0126]

[0127] 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.

[0128] 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.

[0129] Subsequently, 1.0 g of the obtained PPO-GMA (corresponding to 7 mmol of GMA) was added to 9.0 g of N,N-dimethylacrylamide (DMAA) and 90 g of dimethyl sulfoxide as a solvent, and the mixture was reacted at 80°C for 18 hours. The reaction product obtained after the reaction was reprecipitated with hexane and recovered to obtain a block copolymer (1) (structural unit (A):structural unit (B) = GMA:DMAA = 1:14 (molar ratio)) having an epoxy group in the molecule and exhibiting lubricity when wet. The block copolymer (1) thus obtained was １ H-NMR and ATR-IR analyses confirmed the presence of epoxy groups in the molecule. Furthermore, the weight-average molecular weight (Mw) of block copolymer (1) measured by gel permeation chromatography (GPC, polystyrene equivalent) was approximately 1.5 million.

[0130] Example 1 An amino group-containing silicone (1) (KF-859, manufactured by Shin-Etsu Chemical Co., Ltd., functional group equivalent: 6,000 g / mol, reactive silicone (1)) was dissolved in tetrahydrofuran (THF) so that the final concentration in the coating liquid was 2.0% by mass (solution (1)). The block copolymer (1) synthesized in Synthesis Example 1 above was added to and dissolved in the solution (1) so that the final concentration in the coating liquid was 5.0% by mass, thereby preparing coating liquid (1).

[0131] A SUS304 polished rod (manufactured by Misumi Corporation, RGOS3-200, outer diameter: 3.00 mm) was immersed in the coating solution (1), pulled up at a pulling rate of 8 mm / min, and dried at room temperature (25 ° C) for 1 hour to remove THF and form a coating film (1) on the rod surface (rod (1)). Furthermore, this rod (1) was stored in an oven at 130 ° C for 1 hour to heat-treat the coating film (1) (rod (1')). This rod (1') was cooled to room temperature (25 ° C), and a sample (coated rod) (1) having a coating layer (surface lubrication layer) (dry film thickness: 1 μm) containing the block copolymer (1) and the amino group-containing silicone (1) (including the reactant) on the rod surface was prepared.

[0132] Example 2 A sample (coated rod) (2) was produced in the same manner as in Example 1, except that the final concentration of the amino group-containing silicone (1) in the coating liquid was changed to 4.0 mass % to prepare a coating liquid (2), and a coating film (2) was formed using the coating liquid (2).

[0133] Example 3 A sample (coated rod) (3) was produced in the same manner as in Example 1, except that a coating liquid (3) was prepared using a silicone compound (2) prepared as follows instead of the amino group-containing silicone (1) in Example 1, and a coating film (3) was formed using the coating liquid (3). First, polydimethylsiloxane having 3-aminopropyl groups at both ends (manufactured by Merck, number average molecular weight: 2,500, reactive silicone (2)), polydimethylsiloxane having glycidyl ether groups at both ends (manufactured by Merck, number average molecular weight: 800, reactive silicone (3)), and dimethylsilicone oil (manufactured by Shin-Etsu Chemical Co., Ltd., KF-96, non-reactive silicone) were mixed in a mass ratio of 35:5:60 (reactive silicone (2): reactive silicone (3): non-reactive silicone), and the resulting mixture was designated as silicone compound (2).

[0134] The silicone compound (2) was dissolved in tetrahydrofuran (THF) to a concentration of 30% by mass. The solution was then diluted with tetrahydrofuran (THF) to a final concentration of 0.57% by mass (solution (3)). The block copolymer (1) synthesized in Synthesis Example 1 was added to and dissolved in the solution (3) to a final concentration of 5.0% by mass in the coating solution, thereby preparing a coating solution (3).

[0135] Example 4 A sample (coated rod) (4) was produced in the same manner as in Example 3, except that the final concentration of the silicone compound (2) in the coating liquid was changed to 1.1 mass % to prepare a coating liquid (4), and a coating film (4) was formed using the coating liquid (4).

[0136] Comparative Example 1 A comparative coating solution (1) was prepared by dissolving the block copolymer (1) synthesized in the above Synthesis Example 1 in tetrahydrofuran (THF) so that the final concentration in the coating solution was 5.0% by mass.

[0137] A SUS304 polished rod (manufactured by Misumi Corporation, RGOS3-200, outer diameter: 3.00 mm) was immersed in the comparative coating solution (1), pulled up at a pulling rate of 8 mm / min, and dried at room temperature (25 ° C) for 1 hour to remove THF, forming a comparative coating film (1) on the rod surface (comparative rod (1)). Furthermore, this comparative rod (1) was stored in an oven at 130 ° C for 1 hour, and the comparative coating film (1) was heat-treated (comparative rod (1 ')). This comparative rod (1 ') was cooled to room temperature (25 ° C), and a sample (comparative coated rod) (1) having a coating layer (surface lubrication layer) (dry film thickness: 1 μm) containing the block copolymer (1) on the rod surface was prepared.

[0138] Comparative Example 2 A comparative coating solution (2) was prepared by dissolving an amino group-containing silicone (1) (KF-859, manufactured by Shin-Etsu Chemical Co., Ltd., functional group equivalent: 6,000 g / mol) in tetrahydrofuran (THF) so that the final concentration in the coating solution was 4.0 mass %.

[0139] A SUS304 polished rod (manufactured by Misumi Corporation, RGOS3-200, outer diameter: 3.00 mm) was immersed in the comparative coating solution (2), pulled up at a pulling rate of 8 mm / min, and dried at room temperature (25 ° C) for 1 hour to remove THF, forming a comparative coating film (2) on the rod surface (comparative rod (2)). Furthermore, this comparative rod (2) was stored in an oven at 130 ° C for 1 hour, and the comparative coating film (2) was heat-treated (comparative rod (2)). This comparative rod (2) was cooled to room temperature (25 ° C), and a sample (comparative coated rod) (2) having a coating layer (surface lubrication layer) (dry film thickness: 1 μm) containing an amino group-containing silicone (1) on the rod surface was prepared.

[0140] Comparative Example 3 A sample (comparative coated rod) (3) was produced in the same manner as in Comparative Example 2, except that in Comparative Example 2, a comparative coating liquid (3) was prepared using a silicone compound (2) obtained in the same manner as in Example 3 instead of the amino group-containing silicone (1), and a comparative coating film (3) was formed using the comparative coating liquid (3).

[0141] [Contact Angle Measurement] Coating layers (surface lubricating layers) were formed using the coating solutions (1) to (4) prepared in Examples 1 to 4 and the comparative coating solutions (1) to (3) prepared in Comparative Examples 1 to 3 in the same manner as in the preparation of each rod. The contact angles (θ1, θ2, and θ3) of the surface lubricating layers were measured according to the following method: After stirring the coating solution for 1 hour using a stirrer, a surface-polished SUS304 plate was immersed in the coating solution, pulled up at a pull-up rate of 8 mm / min, and dried at room temperature (25°C) for 1 hour to remove THF and form a coating film. Next, the SUS plate on which the coating film was formed was stored in an oven at 130°C for 1 hour to heat-treat the coating film. The SUS plate on which the coating film was formed was then cooled to room temperature (25°C) to obtain samples for contact angle measurement (plates (1) to (4) and comparative plates (1) to (3)) having a coating layer (surface lubricating layer) on the plate surface.

[0142] A dedicated syringe for a contact angle measurement device (manufactured by Asumi Giken Co., Ltd., device name: B100) was filled with purified water and a 25G syringe needle was attached. The syringe was attached to the contact angle measurement device, and the sample for contact angle measurement obtained using the above procedure was placed on the plate surface. Using the image analysis function (pendant drop method), the syringe discharge volume was adjusted so that the droplet was 1.0 μL. The plate was then raised, bringing the droplet into contact with the sample surface. The plate was then lowered, and the droplet was transferred from the syringe needle onto the sample. The time elapsed when the droplet transferred to the sample was defined as the reference time (0 seconds), and the contact angle (contact angle at the specified time) after a specified time (5 seconds (θ1), 1 minute (θ3), 5 minutes (θ2)) was measured using the tangent method. The above measurements were performed at room temperature (25°C) and a relative humidity of 50% RH. The results are shown in Table 1 below. In Table 1 below, the block copolymer (hydrophilic block copolymer) (1) synthesized in Synthesis Example 1 above is represented as "p(GMA-b-DMAA)", and the mass ratio of the silicone compound to the block copolymer (silicone compound:block copolymer) is represented as "silicone compound / block copolymer mass ratio".

[0143]

[0144] [Evaluation of sliding resistance during drying process after wetting] The average tension (sliding resistance during drying process after wetting) was evaluated for the samples (1) to (4) prepared in Examples 1 to 4 above and the comparative samples (1) to (3) prepared in Comparative Examples 1 to 3 above according to the following method.

[0145] A test apparatus 100 for evaluating the sliding resistance (sliding test) of the medical device 10 according to this embodiment will be described with reference to Figures 6 and 7. Figure 6 is a schematic diagram showing the test apparatus 100 for performing a sliding test on the medical device 10 according to this embodiment, and is a diagram showing the medical device 10 sandwiched between a pair of contact members 91, 92. Figure 7 is a schematic diagram showing the test apparatus 100 for performing a sliding test on the medical device 10 according to this embodiment, and is a diagram showing the medical device 10 separated from the pair of contact members 91, 92.

[0146] 6 and 7, the testing device 100 has a pair of contact members 91, 92. The pair of contact members 91, 92 are configured to be able to move toward and away from each other, and when the pair of contact members 91, 92 are in a close proximity, they can clamp the medical device 10 with a predetermined force. A DL1000 manufactured by OAKRIVER TECHNOLOGY can be used as the testing device 100.

[0147] Next, a method for measuring the sliding resistance (average tension) of a sample (rod) 10' as the medical device 10 using the testing device 100 will be described.

[0148] First, each sample (rod) 10' was immersed in tap water for 5 minutes, and then the sample 10' was removed from the water and set in a pinch tester (DL1000, manufactured by OAKRIVER TECHNOLOGY) serving as the test device 100. The pair of contact members 91, 92 were brought close to each other to pinch the sample 10' with a grip force of 500 gf. At this time, grip pads serving as the contact members 91, 92 were made of silicone with a Shore A60 hardness and a pad thickness of 12.35 mm.

[0149] Next, the resistance value was measured while the sample 10' was pulled up at a predetermined speed (test speed) of 8.3 mm / s, and the test stroke (pulling distance) was 25 mm.

[0150] Thereafter, the pair of contact members 91, 92 were moved away from each other to release the sandwiched state of the sample 10', and then the sample 10' was returned to its initial position.

[0151] The above steps were repeated a predetermined number of times, and the average tension (sliding resistance value) was measured a predetermined number of times. In this case, the number of measurements (number of sliding movements) was set to 40, and the average tension was measured, and the results shown in Figure 3 were obtained.

[0152] As shown in Figure 3, the sample of Comparative Example 1 showed large peaks at around 15 and 35 sliding cycles, with the average tension value being extremely high at approximately 600 gf, especially at around 35 sliding cycles. The sample of Comparative Example 2 showed an extremely large average tension value of over 800 gf from the first sliding cycle onwards, and the sample of Comparative Example 3 showed large peaks at around 18 and 27 sliding cycles, with the average tension value exceeding approximately 600 gf even after 27 sliding cycles.

[0153] The stickiness of medical devices with lubricating coatings during use is presumably due to this sudden increase in average tension (the portion showing a clear peak) and the extremely large average tension, particularly the sudden increase in average tension. In contrast, in the samples of Examples 1 to 4, no such clear peak was observed, and the average tension values ​​were less than 500 gf throughout. In other words, it can be said that the stickiness of the samples of Examples 1 to 4 during the transition from a wet state to a dry state was effectively suppressed.

[0154] [Evaluation of sliding resistance in a dry state] The average tension (slidability in a dry state) was evaluated according to the following method for Samples (1) to (4) prepared in Examples 1 to 4 above and Comparative Samples (1) to (3) prepared in Comparative Examples 1 to 3 above. Note that in this evaluation, the same procedures as in the above [Evaluation of sliding resistance during drying after wetting] were carried out, except that the samples before the test were not brought into contact with water and the number of sliding strokes was changed.

[0155] Specifically, each sample was placed in a pinch tester (Oakriver Technology, DL1000) without contact with water 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 (the same grip pads were used as in the "Evaluation of sliding resistance during drying after wetting" section above). The average tension after 10 sliding cycles was measured to evaluate sliding properties. The results are shown in Figure 4 and Table 2.

[0156] [Evaluation of sliding resistance in a wet state] The average tension (slidability in a wet state) was evaluated according to the following method for Samples (1) to (4) prepared in Examples 1 to 4 and Comparative Samples (1) to (3) prepared in Comparative Examples 1 to 3. Note that in this evaluation, the same procedures as in the above [Evaluation of sliding resistance during drying after wetting] were carried out, except that the test was carried out while the samples were immersed in water.

[0157] Specifically, each sample was immersed in tap water and placed in a pinch tester (Oakriver Technology, DL1000) and slid 40 times at a grip force of 500 gf, a test speed of 8.3 mm / s, and a test stroke of 25 mm (the same grip pads were used as in the "Evaluation of sliding resistance during drying after wetting" section above). The average tension after 40 slides was measured to evaluate sliding properties. The results are shown in Figure 5 and Table 2.

[0158] In both the dry and wet states, the lower the average tension, the better the sliding properties are judged to be.

[0159]

[0160] In general, hydrophilic block copolymers are more slippery than silicone compounds in wet conditions. That is, hydrophilic block copolymers exhibit good sliding properties, while silicone compounds exhibit poor sliding properties. Therefore, it is appropriate to compare the Examples with Comparative Examples 2 and 3, which used only silicone compounds, in wet conditions. Specifically, as shown in FIG. 5 , when the coating layer (surface lubrication layer) was formed using only a silicone compound (Comparative Examples 2 and 3), the maximum average tension measured in wet conditions exceeded 200 gf. In contrast, when the coating layer (surface lubrication layer) was formed using a reactive silicone and a hydrophilic block copolymer (Examples 1 to 4), the average tension was 200 gf or less from the first to the fortieth sliding cycle, demonstrating good sliding properties. Furthermore, when a coating layer (surface lubrication layer) was formed using a non-reactive silicone in addition to the reactive silicone and hydrophilic block copolymer (using a reactive silicone, a non-reactive silicone, and a hydrophilic block copolymer) (Examples 3 and 4), it exhibited an average tension that was approximately the same as or lower than that of a coating layer formed using only the hydrophilic block copolymer (Comparative Example 1) (i.e., it exhibited better sliding properties).

[0161] Conversely, some silicone compounds exhibit very low sliding resistance (average tension) in a dry state, and silicone compounds generally tend to be more slippery than hydrophilic block copolymers. Therefore, it is appropriate to compare the Examples with Comparative Example 1, which uses only a hydrophilic block copolymer, in a dry state. Specifically, as shown in FIG. 4 , when a coating layer (surface lubrication layer) is formed using only a hydrophilic block copolymer (Comparative Example 1), the maximum average tension measured in a dry state is approximately 700 gf. In contrast, when a coating layer (surface lubrication layer) is formed using a reactive silicone and a hydrophilic block copolymer (Examples 1 to 4), the average tension is approximately 600 gf or less, demonstrating good sliding properties.

[0162] In summary, in a wet state (Fig. 5), the coating layer (surface lubricating layer) formed using only a silicone compound (Comparative Examples 2 and 3) had an extremely high average tension and poor sliding properties. From these results, it was expected that the coating layer (surface lubricating layer) containing a silicone compound would reduce sliding properties. However, according to Table 2 and Fig. 5 above, even though the coating layer (surface lubricating layer) contained a silicone compound, the samples of Examples 1 to 4 showed excellent sliding properties equivalent to those of the coating layer (surface lubricating layer) formed using only a hydrophilic block copolymer (Comparative Example 1).

[0163] 4, the results show that in the dry state, the samples of Examples 1 to 4 have better sliding properties than the sample of Comparative Example 1, in which the coating layer (surface lubrication layer) was formed using only the hydrophilic block copolymer. This effect is thought to be due to the inclusion of a silicone compound in the surface lubrication layer.

[0164] According to the present invention, after the surface of the medical device (surface lubricating layer) becomes wet, it can maintain high lubricity without developing adhesiveness even during the drying process. Therefore, for example, when performing catheter treatment using a catheter or guidewire, it is not necessary to keep the surface wet every time, or the number of times to spray physiological saline or the like can be reduced. In other words, according to the present invention, such a burdensome operation during the procedure is not necessary, or the number of such operations can be reduced, so that a medical device that reduces the workload during the procedure can be provided.

[0165] This application is based on Japanese Patent Application No. 2023-205991, filed on December 6, 2023, the disclosure of which is incorporated by reference in its entirety.

[0166] 10 Medical device, 1 Base material layer, 1a Base material layer core portion, 1b Base material surface layer, 2 Lubricating layer, 100 Testing apparatus, 10' Sample (rod), 91 Contact member, 92 Contact member.

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 silicone compound, wherein when 1.0 μL of purified water is dropped onto the surface lubricating layer, and the water contact angle 5 seconds after the purified water droplet comes into contact with the surface lubricating layer is θ1, and the water contact angle 5 minutes after the contact is θ2, θ1 is 104° or more and θ2 is 102° or less.

2. The medical device according to claim 1, wherein when the water contact angle θ3 is one minute after a droplet of purified water comes into contact with the surface lubricating layer, said θ3 exceeds 102°.

3. The medical device according to claim 1 or 2, wherein the surface lubricating layer contains the silicone compound and the block copolymer in a mass ratio of 0.1 to 1:

1.

4. The medical device according to claim 1 or 2, wherein the silicone compound comprises a reactive silicone.

5. The reactive silicone has a hydroxyl group (-OH), a carboxyl group, an amino group (-NH ２ 5. The medical device according to claim 4, which has at least one selected from the group consisting of an epoxy group, an ethylenically unsaturated group and an alkoxysilyl group.

6. The medical device according to claim 1 or 2, wherein the reactive monomer having an epoxy group includes 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.

7. 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.

8. 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, the method comprising: 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 silicone compound, and a solvent; and applying the coating liquid onto the base layer.

9. The method according to claim 8, wherein the coating liquid contains the silicone compound in an amount of 0.5 to 5% by mass.

10. The method of claim 8 or 9, wherein the silicone compound comprises a reactive silicone.

11. The reactive silicone has a hydroxyl group (-OH), a carboxyl group, an amino group (-NH ２ 11. The method according to claim 10, wherein the aryl group has at least one selected from the group consisting of an epoxy group, an ethylenically unsaturated group, and an alkoxysilyl group.

12. The method of claim 8 or 9, wherein the solvent comprises at least one selected from the group consisting of methanol, ethanol, isopropyl alcohol, butanol, ethylene glycol, acetone, methyl ethyl ketone, cyclohexanone, ethyl acetate, butyl acetate, tetrahydrofuran (THF), butyl ether, dioxane, hexane, heptane, benzene, toluene, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF).

13. The method according to claim 8 or 9, wherein the reactive monomer having an epoxy group includes at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether.

14. The method according to claim 8 or 9, wherein the hydrophilic monomer comprises at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone.

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