Medical devices and methods of manufacturing medical devices

Abstract

This invention provides a medical device having a surface lubricating layer that maintains excellent lubrication even during the drying process after wetting. The medical device of this invention comprises a substrate layer and a surface lubricating layer supported on at least a portion of the substrate layer. The surface lubricating layer comprises a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, and an organosilicon compound. When 1.0 μL of purified water is added to the surface lubricating layer, and the water contact angle after 5 seconds of contact between the purified water droplet and the surface lubricating layer is defined as θ1, and the water contact angle after 5 minutes of contact is defined as θ2, θ1 is 104° or more, and θ2 is 102° or less.

Description

Technical Field

[0001] This invention relates to medical devices and methods for manufacturing medical devices. Background Technology

[0002] Medical devices such as catheters, guidewires, and indwelling needles, which are inserted into the body, require excellent lubricity to minimize tissue damage to blood vessels and improve operator operability. Therefore, a method of coating a substrate layer with a lubricating hydrophilic polymer has been developed and put into practical use. However, in such medical devices, the hydrophilic polymer can dissolve or peel off from the substrate layer, posing problems regarding safety and maintaining operability. Therefore, the coating of hydrophilic polymers requires not only excellent lubricity but also durability against abrasion and scratching.

[0003] From this perspective, Japanese Patent Application Publication No. 8-33704 (corresponding to US Patent No. 5,670,558) discloses a medical device in which a polymer solution is prepared by dissolving a water-soluble or water-swellable polymer in a solvent that swells a substrate of the medical device. The substrate of the medical device is then immersed in the polymer solution to swell, and the polymer is further cross-linked or polymerized on the surface of the substrate, thereby forming a surface lubricating layer on the surface of the substrate. According to the technology disclosed in Japanese Patent Application Publication No. 8-33704, a surface lubricating layer exhibiting relatively good lubricity can be fixed to the substrate. Summary of the Invention

[0004] Japanese Patent Application Publication No. 8-33704 discloses the preferred use of block copolymers consisting of hydrophilic portions exhibiting lubricity and epoxy-containing portions as water-soluble or water-swellable polymers. Furthermore, when using such block copolymers, the epoxy groups of the block copolymers can be cross-linked through a heating process, forming a surface lubricating layer that is less prone to peeling.

[0005] However, the inventors of this application have discovered that while the surface lubricating layer formed using the aforementioned block copolymer exhibits excellent surface lubricity when wetted with water (e.g., saline solution), it gradually becomes sticky (adhesive) as its surface dries over time. This stickiness as the surface dries significantly reduces the operability of medical devices. For example, on the surfaces of medical devices such as catheters and guidewires, especially in areas where guide sheaths and catheters enter or exit other instruments (primarily the base side), the surface becomes sticky as it dries over time during surgery, causing it to adhere to other instruments. Therefore, to avoid this, it is necessary to maintain the wetness of the medical device surface, for example, by spraying water (e.g., saline solution) onto the surface (surface lubricating layer) of the medical device or by wetting the surface of the medical device with a water-soaked cloth.

[0006] However, such operations would become a workload during surgery. Therefore, there is a need for a medical instrument that, once the surface (surface lubrication layer) of the medical instrument is wetted, does not exhibit stickiness even during the drying process and can maintain high lubricity.

[0007] The present invention was made in view of the above circumstances, and its object is to provide a medical device having a surface lubricating layer that maintains excellent lubricity even during the drying process after wetting. Another object of the present invention is to provide a method for manufacturing the above-mentioned medical device.

[0008] The inventors of this application conducted in-depth research to solve the aforementioned problems. As a result, it was discovered that by forming a surface lubricating layer comprising a hydrophilic block copolymer containing epoxy groups and an organosilicon compound, and by setting the water contact angle of the surface lubricating layer within a specific range, the aforementioned objective can be achieved, thus completing this invention.

[0009] The above-mentioned objectives can be achieved by the present invention having the following structure, which includes the following modes and forms.

[0010] One aspect of the present invention is as follows: 1. A medical device comprising a substrate layer and a surface lubricating layer disposed on at least a portion of the substrate layer, wherein, The aforementioned surface lubricating layer comprises a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, and an organosilicon compound. When 1.0 μL of purified water is added to the aforementioned surface lubricating layer, and the water contact angle after 5 seconds of contact between the purified water droplet and the aforementioned surface lubricating layer is defined as θ1, and the water contact angle after 5 minutes of contact is defined as θ2, The aforementioned θ1 is above 104°, and the aforementioned θ2 is below 102°; 2. In the medical device described in 1. above, preferably, when the water contact angle after the aforementioned purified water droplet comes into contact with the aforementioned surface lubricating layer for 1 minute is set as θ3, the aforementioned θ3 is greater than 102°; 3. In the medical device described in 1. or 2. above, preferably, the aforementioned surface lubricating layer comprises the aforementioned organosilicon compound and the aforementioned block copolymer in a mass ratio of 0.1 to 1:1; 4. In any one of the medical devices described in 1. to 3. above, preferably, the aforementioned organosilicon compound comprises reactive organosilicon; 5. In the medical device described in 4. above, preferably, the aforementioned reactive organosilicon has at least one selected from the group consisting of hydroxyl (-OH), carboxyl, amino (-NH2), epoxy, olefinic unsaturated group and alkoxysilyl group; 6. In any one of the medical devices described in 1 to 5 above, preferably, the aforementioned epoxy-containing reactive monomer comprises at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexyl methyl acrylate, 3,4-epoxycyclohexyl methyl methacrylate, β-methyl glycidyl methacrylate, and allyl glycidyl ether. 7. In any one of the medical devices described in 1 to 6 above, preferably, the aforementioned hydrophilic monomer comprises 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 as follows: 8. A method for manufacturing a medical device, wherein the medical device comprises a substrate layer and a surface lubricating layer disposed on at least a portion of the substrate layer, the manufacturing method comprising: Prepare a coating solution comprising a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, an organosilicon compound, and a solvent. The aforementioned coating liquid is applied onto the aforementioned substrate layer; 9. In the method for manufacturing the medical device described in 8. above, it is preferred that the aforementioned coating liquid contains the aforementioned organosilicon compound in an amount of 0.5 to 5% by mass; 10. In the method of manufacturing the medical device described in 8 or 9 above, preferably, the aforementioned organosilicon compound comprises reactive organosilicon; 11. In the method for manufacturing the medical device described in 10 above, preferably, the aforementioned reactive organosilicon has at least one selected from the group consisting of hydroxyl (-OH), carboxyl, amino (-NH2), epoxy, olefinic unsaturated group and alkoxysilyl group; 12. In the method of manufacturing the medical device according to any one of 8. to 11. above, preferably, the solvent comprises at least one selected from the group consisting of methanol, ethanol, isopropanol, 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 of manufacturing the medical device according to any one of 8. to 12. above, preferably, the aforementioned epoxy-containing reactive monomer comprises at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexyl acrylate, 3,4-epoxycyclohexyl methacrylate, β-methyl glycidyl methacrylate and allyl glycidyl ether; 14. In the method of manufacturing the medical device according to any one of 8 to 13 above, preferably, the aforementioned hydrophilic monomer comprises at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate and N-vinylpyrrolidone. Attached Figure Description

[0012] [ Figure 1 This is a partial cross-sectional view schematically illustrating a representative embodiment of the medical device according to the present invention, showing the surface layered structure.

[0013] [ Figure 2 As Figure 1 The following are schematic cross-sectional views illustrating different configurations of the surface layering structure, as described in the implementation examples.

[0014] [ Figure 3 The graphs show the results of the clamping test (Wet-Dry test) during the drying process after wetting for each sample in the Examples and Comparative Examples.

[0015] [ Figure 4 The graphs show the results of the clamping test (Dry test) under dry conditions (in air) for each sample in the examples and comparative examples.

[0016] [ Figure 5 The graphs show the results of the clamping test (Wet test) in a wet state (in water) for each sample in the examples and comparative examples.

[0017] [ Figure 6 [A schematic diagram of a test apparatus for performing a sliding test on a medical device according to this embodiment is shown, and a diagram showing a pair of abutting parts clamped into the medical device is shown.]

[0018] [ Figure 7 [A schematic diagram of a test apparatus for performing a sliding test on a medical device according to this embodiment is shown, and a diagram showing the medical device separated from a pair of abutting parts is shown.] Detailed Implementation

[0019] One aspect of the present invention relates to a medical device comprising a substrate layer and a surface lubricating layer supported on at least a portion of the substrate layer. The surface lubricating layer comprises a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, and an organosilicon compound. Furthermore, in one aspect of the medical device of the present invention, when 1.0 μL of purified water is added to the surface lubricating layer, and the water contact angle after 5 seconds of contact between the purified water droplet and the surface lubricating layer is defined as θ1, and the water contact angle after 5 minutes of contact is defined as θ2, θ1 is 104° or more, and θ2 is 102° or less. Hereinafter, the medical device having the above configuration will also be referred to as "the medical device of the present invention" or "medical device".

[0020] In this specification, the structural unit (A) derived from the reactive monomer containing an epoxy group will be referred to as "the structural unit (A) of this invention" or "structural unit (A)". Similarly, the structural unit (B) derived from the hydrophilic monomer will be referred to as "the structural unit (B) of this invention" or "structural unit (B)". Furthermore, the block copolymer having structural units (A) and (B) will be referred to as "the block copolymer of this invention", "hydrophilic block copolymer", or "block copolymer".

[0021] In this specification, when a structural unit is specified as "derived from" a monomer, it means that the structural unit is generated by the breaking of one bond in the polymerizable unsaturated double bond of the corresponding monomer.

[0022] In this specification, the term "(meth)acrylic" includes both acrylic acid and methacrylic acid. Therefore, for example, the term "(meth)acrylic" includes both acrylic acid and methacrylic acid. Similarly, the term "(meth)acryloyl" includes both acryloyl and methacryloyl. Likewise, the term "(meth)acryloyl" includes both acryloyl and methacryloyl. Furthermore, similarly, the term "(meth)acrylate" includes both acrylate and methacrylate. For example, the term "(meth)acrylate alkoxyalkyl ester" includes both alkoxyalkyl acrylate and alkoxyalkyl methacrylate.

[0023] In this specification, the term "X~Y" indicating a range includes both X and Y, meaning "above X and below Y". Additionally, "X and / or Y" refers to at least one of X and Y, including X alone, Y alone, and combinations of X and Y.

[0024] Unless otherwise specified, the determination of operation and physical properties shall be carried out at room temperature (20-25°C) and relative humidity 40-50%RH.

[0025] The medical device of the present invention has a surface lubricating layer comprising a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, and an organosilicon compound, and the water contact angle of the surface lubricating layer is within a specific range. Specifically, in the case of the medical device of the present invention, when 1.0 μL of purified water is added to the surface lubricating layer, the water contact angle (θ1) of the added purified water droplet after contacting the surface lubricating layer for 5 seconds is 104° or more, and the water contact angle (θ2) of the droplet after contacting the surface lubricating layer for 5 minutes is 102° or less.

[0026] The inventors of this application hypothesize that the stickiness (tackiness) during the drying process after wetting is caused by the hydrophilic block copolymer that imparts good sliding properties to the surface lubricating layer. More specifically, it is believed that when the hydrophilic block copolymer is wet, the surface lubricating layer can exert good sliding properties, but as the hydrophilic block copolymer (including the surface lubricating layer containing the hydrophilic block copolymer) gradually dries, it can no longer exert the same sliding properties as when wet, thus producing the aforementioned stickiness (tackiness).

[0027] In this regard, the medical device of the present invention further comprises an organosilicon compound in its surface lubricating layer containing a hydrophilic block copolymer. Here, the block copolymer contained in the surface lubricating layer functions as a hydrophilic component, while the organosilicon compound contained in the surface lubricating layer functions as a hydrophobic component. Since the surface lubricating layer of the medical device of the present invention contains an organosilicon compound, and the water contact angle θ1 (the water contact angle 5 seconds after the surface lubricating layer contacts a water droplet) is a specific value or higher, it can be considered that its surface has moderate hydrophobicity immediately after contact with a water droplet.

[0028] Furthermore, it is speculated that such moderate hydrophobicity is due to the presence of organosilicon compounds on the surface of the surface lubricating layer, resulting in a moderately reduced proportion of the aforementioned hydrophilic block copolymers on that surface.

[0029] Therefore, on the surface of the surface lubricating layer of the medical device according to the present invention, as described above, since the proportion of hydrophilic block copolymer is moderately small, the effects of drying of the hydrophilic block copolymer (i.e., the generation of stickiness) can be mitigated. Therefore, according to the present invention, a medical device having a surface lubricating layer that exhibits excellent lubrication maintenance properties even during the drying process after wetting can be provided.

[0030] Furthermore, the water contact angle θ2 (the water contact angle 5 minutes after the surface lubricating layer comes into contact with a water droplet) of the surface lubricating layer of the medical device involved in this invention is below a specific value. This property is believed to be due to the fact that, after the surface lubricating layer comes into contact with water (becoming wet), the hydrophilic block copolymer contained in the surface lubricating layer exhibits hydrophilicity over time. Therefore, although the surface lubricating layer contains organosilicon compounds, it can maintain good hydrophilicity, resulting in high lubricity (surface lubricity).

[0031] As can be seen from the above, the medical device of the present invention can achieve the following expected effects: while avoiding the problem of stickiness (adhesion) during the drying process after wetting, it maintains excellent lubricity (surface lubricity). It should be noted that the above mechanism is speculative and does not limit the technical scope of the present invention.

[0032] The embodiments of the present invention will be described below. It should be noted 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 combined arbitrarily to form other embodiments. For ease of explanation, the dimensions of the accompanying drawings are exaggerated and sometimes differ from the actual proportions. Additionally, please refer to the accompanying drawings... Figure 1 As embodiments of the present invention are described, the same reference numerals are used for the same elements in the description of the drawings, and repeated descriptions are omitted.

[0033] Throughout this specification, unless otherwise specified, singular expressions should be understood to also include the concept of their plural forms. Therefore, unless otherwise specified, articles in the singular form (e.g., "a," "an," "the," etc. in the English context) should be understood to also include the concept of their plural forms. Furthermore, unless otherwise specified, terminology used in this specification should be understood to be used in the meaning commonly understood in the art. Therefore, unless otherwise defined, all specialized and technical terms used in this specification have the same meaning as commonly understood by those skilled in the art to which this invention pertains. In cases of conflict, this specification (including definitions) takes precedence.

[0034] [Medical Equipment] The medical device of the present invention comprises a substrate layer and a surface lubricating layer supported on at least a portion of the substrate layer. The surface lubricating layer comprises a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, and an organosilicon compound. Furthermore, the surface lubricating layer has the following characteristics: When 1.0 μL of purified water is added to the surface lubricating layer, the water contact angle after 5 seconds of contact between the purified water droplet and the surface lubricating layer is defined as θ1, and the water contact angle after 5 minutes of contact between the purified water droplet and the surface lubricating layer is defined as θ2. θ1 is greater than or equal to 104°, and θ2 is less than or equal to 102°.

[0035] Hereinafter, preferred embodiments of the medical device of the present invention will be described with reference to the accompanying drawings.

[0036] Figure 1 A partial cross-sectional view of the surface layered structure of a representative embodiment of the medical device according to the present invention. Figure 2 As Figure 1 The illustrated embodiment schematically shows partial cross-sectional views of different surface layering structures. It should be noted that... Figure 1 and Figure 2 The reference numerals in the figures denote the following: reference numeral 1 denotes the substrate layer; reference numeral 1a denotes the core of the substrate layer; reference numeral 1b denotes the surface layer of the substrate; reference numeral 2 denotes the surface lubricating layer; and reference numeral 10 denotes the medical device of the present invention.

[0037] like Figure 1 , Figure 2As shown, the medical device 10 of this embodiment includes a substrate layer 1 and a surface lubricating layer 2 comprising a block copolymer, disposed on at least a portion of the substrate layer 1 (an example shown in the figure is a surface entirely (the entire surface) of the substrate layer 1). It should be noted that... Figure 1 , Figure 2 In this invention, the surface lubrication layer 2 is formed on both sides of the substrate layer 1, but the invention is not limited to the above-described form. It can also be formed on one side of the substrate layer 1, or on a portion of one or both sides of the substrate layer 1, or any other form.

[0038] The medical device will be described in detail below, with each component as a separate part.

[0039] <Substrate Layer (Substrate)> The substrate layer used in this embodiment can be made of any material, and there are no particular limitations on the material. Specifically, the materials constituting the substrate layer 1 may include metallic materials, polymeric materials, and ceramics.

[0040] Among the materials constituting the substrate layer 1, there are no particular restrictions on the metallic materials used; commonly used metallic materials for medical devices such as catheters, guidewires, and indwelling needles can be used. Specifically, examples include various stainless steels such as SUS304, SUS314, SUS316, SUS316L, SUS420J2, and SUS630, as well as various alloys such as gold, platinum, silver, copper, nickel, cobalt, titanium, iron, aluminum, tin, nickel-titanium alloys, nickel-cobalt alloys, cobalt-chromium alloys, and zinc-tungsten alloys. One of these materials can be used alone, or two or more can be used in combination. The most suitable metallic material for the intended use of the substrate layer in catheters, guidewires, indwelling needles, etc., should be selected from the above-mentioned metallic materials.

[0041] Furthermore, there are no particular limitations on the polymeric materials (resin materials or elastomer materials) used in the aforementioned substrate layer 1; polymeric materials commonly used in medical devices such as catheters, guides, guidewires, and indwelling needles can be used. Specifically, examples include polyamide resins, polyethylene resins, polypropylene resins and other polyolefin resins, modified polyolefin resins, cyclic polyolefin resins, epoxy resins, polyurethane resins, diallyl phthalate resins (allyl resins), polycarbonate resins, fluororesins, amino resins (urea-formaldehyde resins, melamine resins, benzoguanamine resins), polyethylene terephthalate resins, polybutylene terephthalate resins and other polyester resins, styrene resins, acrylic resins, polyacetal resins, vinyl acetate resins, phenolic resins, vinyl chloride resins, silicone resins (silicone resins), polyether resins, and polyimide resins.

[0042] In addition, thermoplastic elastomers such as polyurethane elastomers, polyester elastomers, and polyamide elastomers (nylon elastomers) can also be used as materials for the substrate layer.

[0043] These polymer materials can be used alone, as a mixture of two or more, or as copolymers of two or more monomers constituting any of the aforementioned resins or elastomers. Among the aforementioned polymer materials, the most suitable polymer material should be selected for the substrate layer of the catheter, guidewire, indwelling needle, etc., intended for use.

[0044] In addition, there are no particular restrictions on the shape of the substrate layer 1 mentioned above. It can be appropriately selected as sheet, wire (filament), rod, tube, etc., depending on the application.

[0045] Here, regarding the substrate layer 1, the substrate layer 1 can be composed of any of the aforementioned materials. The substrate layer 1 can also be a multilayer structure formed by stacking multiple layers of different materials, or a structure formed by connecting components of different materials for various parts of a medical device. Alternatively, as... Figure 2 As shown, the structure can also be as follows: A substrate surface layer 1b is formed by coating the surface of the substrate core 1a, which is made of any of the aforementioned materials, with another of the aforementioned materials using an appropriate method. Examples of the latter include: a structure in which a metal material is coated onto the surface of the substrate core 1a, which is made of a resin material, using an appropriate method (plating, metal vapor deposition, sputtering, or other conventionally known methods) to form the substrate surface layer 1b; a structure in which a polymer material softer than the reinforcing material, such as a metal material or ceramic material, is coated onto the surface of the substrate core 1a, which is made of a hard reinforcing material such as a metal material or ceramic material, using an appropriate method (dipping, spraying, coating, printing, or other conventionally known methods); or a structure in which the reinforcing material forming the substrate core 1a is combined with a polymer material to form the substrate surface layer 1b. Furthermore, the substrate core 1a can also be a multilayer structure formed by stacking multiple layers of different materials, or a structure formed by connecting components made of different materials for various parts of a medical device. Alternatively, other intermediate layers (not shown) may be further formed between the core layer 1a and the surface layer 1b of the substrate layer. Furthermore, the surface layer 1b of the substrate may be a multilayer structure made of multiple layers of different materials, or a structure formed by connecting parts of a medical device made of different materials.

[0046] <Surface Lubricating Layer (Coating)> A surface lubricating layer is supported on at least a portion of the substrate layer 1. The reason for supporting the surface lubricating layer 2 on at least a portion of the surface of the substrate layer 1 is that, in medical devices such as catheters, guidewires, and indwelling needles intended for use, it is not necessary for the entire surface (surface as a whole) of these medical devices to be lubricated when wet; only the surface portion (sometimes a portion, sometimes all) where lubrication when wet is required is supported by the surface lubricating layer. Therefore, as described above, the surface lubricating layer includes the following form: Figure 1 , Figure 2 The forms shown are formed in a manner where both sides of the covered substrate layer are integral; forms are formed in a manner where only one side of the covered substrate layer is integral; forms are formed in a manner where parts of both sides of the covered substrate layer are covered in the same or different forms; forms are formed in a manner where only a part of one side of the covered substrate layer is covered; and so on.

[0047] (Water contact angles θ1, θ2 and θ3) Regarding the surface lubricating layer, when 1.0 μL of purified water is added to the surface lubricating layer, the water contact angle (θ1) after 5 seconds of contact between the added water droplet and the surface lubricating layer is 104° or more. Similarly, regarding the surface lubricating layer, when 1.0 μL of purified water is added to the surface lubricating layer, the water contact angle (θ2) after 5 minutes of contact between the added water droplet and the surface lubricating layer is 102° or less. Furthermore, regarding the surface lubricating layer, similarly, when 1.0 μL of purified water is added to the surface lubricating layer, the water contact angle (θ3) after 1 minute of contact between the added water droplet and the surface lubricating layer is preferably greater than 102°. In this specification, the water contact angles θ1, θ2, and the water contact angle θ3 (described later) are measured at room temperature (25°C) and a relative humidity of 50% RH, and the specific measurement method is the method described in the examples. In addition, in this specification, when 1.0 μL of purified water is added to the surface lubricating layer, the water contact angle after 5 seconds (the time point after 5 seconds), after 5 minutes (the time point after 5 minutes), and after 1 minute (the time point after 1 minute) are respectively abbreviated as "water contact angle θ1", "water contact angle θ2", and "water contact angle θ3".

[0048] From the viewpoint of effectively suppressing stickiness (tackiness) 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. Furthermore, there is no particular limitation on the upper limit of the water contact angle θ1, but from the viewpoint of maintaining good sliding properties (surface lubricity) when wetted, it is preferably 140° or less, more preferably 130° or less.

[0049] 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°.

[0050] Furthermore, from the viewpoint of obtaining excellent sliding properties (surface lubricity) when wetted, the water contact angle θ2 is preferably 101° or less, more preferably 100° or less. Additionally, there is no particular limitation on the lower limit of the water contact angle θ2, but from the viewpoint of effectively suppressing stickiness (tackiness) 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.

[0051] Therefore, in one embodiment of the present invention, the water contact angle θ2 is preferably 78–102°, more preferably 80–102°, even more preferably 85–102°, even more preferably 85–101°, and particularly preferably 90–100°. Furthermore, when the water contact angle θ2 is within any of these ranges, the aforementioned water contact angle θ1 is preferably within any of the aforementioned preferred ranges.

[0052] Furthermore, from the viewpoint of effectively suppressing stickiness (tackiness) 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. Additionally, there is no particular limitation on the upper limit of the water contact angle θ3, but from the viewpoint of maintaining good sliding properties (surface lubricity) when wetted, it is preferably 130° or less, more preferably 125° or less, and particularly preferably 120° or less.

[0053] Therefore, in one embodiment of the present invention, the water contact angle θ3 is preferably 102 to 130°, more preferably greater than 102° and less than 130°, even more preferably 103 to 130°, even more preferably 105 to 125°, and particularly preferably 110 to 120°.

[0054] Furthermore, in other embodiments, the water contact angle θ2 of the surface lubricating layer can be 78–102°, and the water contact angle θ3 can be 102–130°. In other preferred embodiments, the water contact angle θ2 of the surface lubricating layer can be 78–102°, and the water contact angle θ3 can be greater than 102° and less than 130°. In other preferred embodiments, the water contact angle θ2 of the surface lubricating layer can be 80–102°, and the water contact angle θ3 can be 103–130°. In other preferred embodiments, the water contact angle θ2 of the surface lubricating layer can be 85–101°, and the water contact angle θ3 can be 105–125°. In other preferred embodiments, the water contact angle θ2 of the surface lubricating layer can be 90–100°, and the water contact angle θ3 can be 110–120°.

[0055] The water contact angles θ1, θ2, and θ3 of the surface lubricating layer can be appropriately controlled by the mass ratio of the block copolymer and organosilicon compound contained in the surface lubricating layer, and by the heating and drying conditions after the coating liquid containing the above components is applied to the substrate layer. It should be noted that the details of the mass ratio of each component constituting the surface lubricating layer, the heating and drying conditions, etc., will be described later.

[0056] (block copolymer) In this invention, a block copolymer forms a surface lubricating layer supported on at least a portion of the substrate layer. That is, in the medical device of this invention, the surface lubricating layer comprises a block copolymer. It should be noted that "supported" refers to a state in which the surface lubricating layer is immobilized in a manner that makes it difficult to detach from the surface of the substrate layer. This includes not only a state in which the entire surface of the substrate layer is completely covered by the surface lubricating layer, but also a state in which only a portion of the surface of the substrate layer is covered by the surface lubricating layer, i.e., a state in which the surface lubricating layer is only attached to a portion of the surface of the substrate layer.

[0057] The block copolymers involved in this invention have structural units (A) derived from reactive monomers containing epoxy groups and structural units (B) derived from hydrophilic monomers.

[0058] The reactive monomers containing epoxy groups that constitute the block copolymers have epoxy groups as reactive groups. By introducing such structural units (A) derived from reactive monomers into the block copolymers, the epoxy groups are ring-opened, and cross-linking (bonding) occurs between the block copolymers, thereby improving the film strength of the surface lubricating layer. In addition, when the substrate layer is a resin material, cross-linking (bonding) between the block copolymer and the substrate layer can also be achieved using the ring-opened epoxy groups.

[0059] The reactive monomers constituting the block copolymers are not particularly limited as long as they have epoxy groups, and known compounds can be used. However, from the perspective of easily controlling the crosslinking or polymerization of the block copolymers, the epoxy-containing reactive monomers preferably include at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate (GMA), 3,4-epoxycyclohexyl acrylate, 3,4-epoxycyclohexyl methacrylate, β-methyl glycidyl methacrylate, and allyl glycidyl ether.

[0060] Among these, considering the potential to further promote cross-linking reactions and ease of manufacture, glycidyl methacrylate is more preferred, and glycidyl methacrylate is particularly preferred. That is, in a more preferred embodiment of the present invention, the epoxy-containing reactive monomer is at least one of glycidyl acrylate and glycidyl methacrylate. Furthermore, in a particularly preferred embodiment of the present invention, the epoxy-containing reactive monomer is glycidyl methacrylate.

[0061] The aforementioned reactive monomers can be used alone or in combination with two or more. That is, the structural unit (A) derived from the reactive monomer can be a homopolymer composed of a single reactive monomer, or a copolymer composed of two or more of the aforementioned reactive monomers. It should be noted that when using two or more, the structural unit (A) can be a block copolymer or a random copolymer.

[0062] The hydrophilic monomers constituting the block copolymer exhibit swelling properties upon contact with bodily fluids and aqueous solvents, thus imparting lubricity (surface lubricity) to medical devices. Therefore, by introducing such structural units (B) derived from hydrophilic monomers into the block copolymer, the lubricity (surface lubricity) of the medical device is improved, thereby reducing friction when the medical device comes into contact with luminal walls such as blood vessel walls.

[0063] There are no particular limitations on the hydrophilic monomers constituting the block copolymers, provided they possess the aforementioned properties; known compounds can be used. Examples include acrylamide or derivatives thereof, vinylpyrrolidone, acrylic acid or methacrylic acid and their derivatives, polyethylene glycol acrylates and their derivatives, monomers having sugars or phospholipids in their side chains, and water-soluble monomers such as maleic anhydride. More specifically, examples include acrylic acid, methacrylic acid, N-methacrylamide, N,N-dimethylacrylamide (DMAA), acrylamide, acryloylmorpholine, N,N-dimethylaminoethyl acrylate, N-vinylpyrrolidone, 2-methacryloyloxyethyl phosphoric acid choline, 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-cyclohexanediethanol mono(meth)acrylate, and (meth)propyl... The hydrophilic monomers include 1-chloro-2-hydroxypropyl acrylate, diethylene glycol mono(meth)acrylate, 1,6-hexanediol mono(meth)acrylate, pentaerythritol tri(meth)acrylate, dipentaerythritol penta(meth)acrylate, neopentyl glycol mono(meth)acrylate, trimethylolpropane di(meth)acrylate, trimethylolethane di(meth)acrylate, 2-hydroxy-3-phenyloxypropyl methacrylate, 4-hydroxycyclohexyl methacrylate, 2-hydroxy-3-phenyloxy methacrylate, 4-hydroxycyclohexyl methacrylate, cyclohexanediol mono(meth)acrylate, poly(ethylene glycol) methyl ether acrylate, and poly(ethylene glycol) methyl ether methacrylate. From the viewpoint 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.

[0064] In particular, considering the excellent lubricity, ease of synthesis, and operability, N,N-dimethylacrylamide, acrylamide, or 2-hydroxyethyl methacrylate is more preferred, and N,N-dimethylacrylamide is especially 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.

[0065] The aforementioned hydrophilic monomers can be used alone or in combination with two or more. That is, the structural unit (B) derived from the hydrophilic monomer can be a homopolymer composed of a single hydrophilic monomer, or a copolymer composed of two or more of the aforementioned hydrophilic monomers. It should be noted that when using two or more, the structural unit (B) can be a block copolymer or a random copolymer.

[0066] The block copolymer has structural units (A) derived from the aforementioned reactive monomer and structural units (B) derived from the aforementioned hydrophilic monomer. Regarding the ratio of structural units (A) to structural units (B), there are no particular limitations as long as the aforementioned effects are achieved. Considering good lubricity, lubrication retention, coating strength, and adhesion to the substrate layer, the ratio of structural units (A) to structural units (B) (molar ratio of structural unit (A): structural unit (B)) is preferably 1:2 to 1:100, more preferably 1:2 to 1:50, further preferably 1:5 to 1:50, and particularly preferably 1:10 to 1:30. Within this range, the surface lubricating layer can fully utilize lubricity through structural units (B), and can also fully utilize coating strength, adhesion to the substrate layer, and durability through structural units (A). It should be noted that the molar ratio of structural units (A): structural units (B) can be controlled by adjusting the charge ratio (molar ratio) of each monomer during the manufacturing stage of the block copolymer. Therefore, in the manufacturing stage of the block copolymer, the molar ratio of the epoxy-containing reactive monomer to the hydrophilic monomer is preferably 1:2 to 1:100, more preferably 1:2 to 1:50, further preferably 1:5 to 1:50, and particularly preferably 1:10 to 1:30. It should be noted that the molar ratio of the above-mentioned structural unit (A):structural unit (B) can be determined, for example, by NMR analysis of the copolymer. 1 H-NMR measurement, 13 Confirmation can be made through methods such as C-NMR measurements.

[0067] The block copolymers involved in this invention must contain structural units (A) and (B), but may also contain other structural units besides these. Examples of other structural units in block copolymers include adipic acid, glutaric acid, triethylene glycol, and tripropylene glycol. The monomers constituting the other structural units may be used individually 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. It should be noted that when using two or more monomers constituting the aforementioned other structural units, the segments formed by these monomers may be in the form of block copolymers, random copolymers, or alternating copolymers.

[0068] When the block copolymer of the present invention has other structural units, the content of the other structural units is preferably greater than 0 mol% and less than 5 mol% relative to the total number of structural units constituting the block copolymer. That is, in the block copolymer of the present invention, when the total number of all structural units constituting the block copolymer is set to 100 mol%, the total content of structural unit (A) and structural unit (B) is preferably 95 mol% or more (upper limit: less than 100 mol%). More preferably, the block copolymer of the present invention is substantially composed of structural unit (A) and structural unit (B) (the content of other structural units = greater than 0 mol% and less than 5 mol%). In this form, the block copolymer of the present invention can achieve a good balance between the durability brought by structural unit (A) and the lubricity (surface lubricity) brought by structural unit (B). Preferably, the block copolymer of the present invention does not contain the above-mentioned other structural units (the content of other structural units = 0 mol%).

[0069] It should be noted that the composition of each structural unit (structural units (A) and (B), and other structural units) can be determined by known methods. For example, by measuring the composition of block copolymer solutions... 1 The integral ratio of each signal intensity in the H-NMR spectrum can be used to determine the composition (molar ratio) of structural units.

[0070] In one embodiment of the present invention, the block copolymer involved in the present invention is substantially 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-epoxycyclohexyl acrylate, 3,4-epoxycyclohexyl methacrylate, β-methyl glycidyl 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 above structural unit (A) and the above structural unit (B).

[0071] In one embodiment of the present invention, the block copolymer involved in the present invention is substantially composed of structural units (A) derived from at least one of the reactive monomers of glycidyl acrylate and glycidyl methacrylate, and structural units (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 above structural units (A) and the above structural units (B).

[0072] In one embodiment of the present invention, the block copolymer involved in the present invention is substantially composed of structural units (A) derived from glycidyl methacrylate (an epoxy-containing reactive monomer) and structural units (B) derived from N,N-dimethylacrylamide (a hydrophilic monomer), or is composed only of the above-mentioned structural units (A) and the above-mentioned structural units (B).

[0073] From the viewpoint of solubility, the weight-average molecular weight of the block copolymer is preferably 10,000 to 10,000,000. From the viewpoint of ease of preparing the coating solution, the weight-average molecular weight of the block copolymer is more preferably 100,000 to 5,000,000. In this specification, "weight-average molecular weight" is the value determined by gel permeation chromatography (GPC) using polystyrene as a standard.

[0074] There are no particular limitations on the manufacturing method of block copolymers. For example, conventionally known polymerization methods such as living radical polymerization, polymerization using macromolecular initiators, and polycondensation can be used. Among these, living radical polymerization or polymerization using macromolecular initiators is preferred from the perspective of easy control over the molecular weight and molecular weight distribution of structural units (sites) derived from reactive monomers and structural units (sites) derived from hydrophilic monomers. As for living radical polymerization, there are no particular limitations. For example, the methods described in Japanese Patent Application Publication No. 11-263819, Japanese Patent Application Publication No. 2002-145971, and Japanese Patent Application Publication No. 2006-316169, as well as atom transfer radical polymerization (ATRP), can be applied in the same way or with appropriate modifications. In addition, in polymerization methods using macromolecular initiators, for example, after preparing a macromolecular initiator having reactive sites containing reactive functional groups and free radical polymerizable groups such as peroxy groups, the macromolecular initiator is polymerized with monomers used to form hydrophilic sites, thereby producing block copolymers having hydrophilic and reactive sites.

[0075] In addition, the polymerized block copolymer is preferably purified by conventional purification methods such as reprecipitation, dialysis, ultrafiltration, and extraction.

[0076] (Organosilicon compounds) There are no particular restrictions on the organosilicon compounds contained in the surface lubricating layer; they can be reactive organosilicones, non-reactive organosilicones, or combinations thereof.

[0077] From the viewpoint of preventing phase separation from the block copolymer constituting the surface lubrication layer, forming a uniform film, and stably obtaining sliding properties (surface lubricity), the organosilicon compound preferably contains reactive organosilicon. In this way, by forming a uniform film, it is easier to suppress stickiness (tackiness) during the drying process after wetting. Furthermore, by including reactive organosilicon along with the block copolymer, they can undergo a cross-linking reaction to form a network structure. It is presumably that as a result, the mobility of the block copolymer can be reduced, making it easier to suppress stickiness (tackiness) during the drying process after wetting. Moreover, the network of block copolymer and reactive organosilicon formed through the above cross-linking reaction easily swells upon wetting, resulting in excellent surface lubricity, and this excellent surface lubricity can be maintained for a long time.

[0078] Here, "reactive organosilicon" refers to an organosilicon compound having reactive groups that can react with reactive functional groups contained in block copolymers, such as epoxy groups (or glycidyl groups).

[0079] Therefore, in this specification, the phrase "the surface lubricating layer comprises reactive organosilicon (as an organosilicon compound)" includes not only the form containing unreacted reactive organosilicon, but also the form containing reactants of reactive organosilicon and block copolymers in addition to reactive organosilicon. Furthermore, the phrase "the surface lubricating layer comprises reactive organosilicon and block copolymers (as organosilicon compounds)" includes not only the form containing unreacted reactive organosilicon and unreacted block copolymers, but also the form containing reactants of reactive organosilicon and block copolymers. Here, the reaction rate between the reactive organosilicon and the block copolymer may not be 100%. That is, the surface lubricating layer may further contain at least one of unreacted reactive organosilicon and unreacted block copolymers in addition to the aforementioned reactants (reaction products).

[0080] The reactive groups present in the reactive organosilicon are not particularly limited, and examples include hydroxyl (-OH), carboxyl, amino (-NH2), epoxy, olefinic unsaturated groups, and alkoxysilyl groups. Therefore, in one embodiment, the reactive organosilicon preferably has at least one group selected from the group consisting of hydroxyl (-OH), carboxyl, amino, epoxy, olefinic unsaturated groups, and alkoxysilyl groups. More preferably, the reactive organosilicon has at least one group selected from the group consisting of hydroxyl, carboxyl, amino, and epoxy groups. Particularly preferred is that the reactive organosilicon has amino and / or epoxy groups. It should be noted that the epoxy group may be included in the form of a glycidyl group.

[0081] As for reactive organosilicones, there are no particular limitations as long as they possess the aforementioned reactive groups. Examples include amino-modified organosilicones, epoxy-modified organosilicones, carboxyl-modified organosilicones, (meth)acrylic acid-modified ((meth)acryloyl-modified) organosilicones, methanol-modified organosilicones, and silanol-modified organosilicones. Among these, amino-modified organosilicones and / or epoxy-modified organosilicones are preferred as reactive organosilicones, considering their superior reactivity with the epoxy groups contained in block copolymers. One type of reactive organosilicon may be used alone, or two or more may be used in combination. When two or more types are used, the content of reactive organosilicones indicates their total amount.

[0082] In one embodiment, the organosilicon compound constituting the surface lubricating layer may be a reactive organosilicon. That is, the organosilicon compound contained in the surface lubricating layer may be in a form that is substantially composed only of reactive organosilicon. Here, "the organosilicon compound contained in the surface lubricating layer is in a form that is substantially composed only of reactive organosilicon" means that the surface lubricating layer is intentionally designed to not contain any organosilicon compounds other than reactive organosilicon (i.e., non-reactive organosilicon). Therefore, a surface lubricating layer that inevitably contains trace amounts of organosilicon compounds other than reactive organosilicon due to raw materials, manufacturing methods, etc., is included in the above-described form. In other words, the above-described form refers to a surface lubricating layer containing no organosilicon compounds other than reactive organosilicon.

[0083] In a preferred embodiment, the organosilicon compound constituting the surface lubricating layer further comprises non-reactive organosilicon in addition to the aforementioned reactive organosilicon. That is, the organosilicon compound contained in the surface lubricating layer preferably comprises both reactive and non-reactive organosilicon. With this configuration, it is easier to obtain an effect that suppresses stickiness during the drying process after wetting, and the sliding properties in the wet state are also excellent. Here, "non-reactive organosilicon" refers to an organosilicon compound that does not have reactive groups.

[0084] As a non-reactive organosilicon, there are no particular limitations as long as the organosilicon does not have the aforementioned reactive groups; examples include dimethyl organosilicon, methylphenyl organosilicon, and methylhydro organosilicon. Among these, dimethyl organosilicon is preferred as a non-reactive organosilicon. One of the aforementioned non-reactive organosilicones can be used alone, or two or more can be used in combination. When two or more are used, the content of the non-reactive organosilicones represents their total amount.

[0085] Commercially available or synthetic organosilicon compounds can be used as the above-mentioned compounds. Commercially available reactive organosilicon compounds 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 Industry Co., Ltd.). In addition, commercially available non-reactive organosilicon products include SH-200, SH510, SH550, SH710 (manufactured by TorayDow Corning Co., Ltd.), KF-96, KF-96H, KF-965, KF-968, KF-50, KF-53, and KF-54 (manufactured by Shin-Etsu Chemical Industry Co., Ltd.).

[0086] Furthermore, as a synthetic method, known methods can be directly used, or appropriately modified, to synthesize organosilicon compounds. Examples of methods for synthesizing reactive organosilicones include reacting an amino-containing silane with a silanol-containing polydiorganosiloxane, and reacting an epoxy-containing silane with a silanol-containing polydiorganosiloxane. The reaction of silane compounds containing these reactive groups with silanol-containing polydiorganosiloxanes can be carried out using solvents as needed, by stirring and heating these compounds. Preferably, the reaction is carried out with the amino-containing silane / epoxy-containing silane ratio being 1-5% by mass and the silanol-containing polydiorganosiloxane ratio being 95-99% by mass (total 100% by mass).

[0087] Examples of amino-containing silanes 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.

[0088] Examples of epoxy-containing silanes include γ-epoxypropoxypropyltrimethoxysilane, γ-epoxypropoxypropylmethyldimethoxysilane, β-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, β-(3,4-epoxycyclohexyl)ethylmethyldimethoxysilane, β-(3,4-epoxycyclohexyl)ethyltriethoxysilane, and β-(3,4-epoxycyclohexyl)ethylmethyldiethoxysilane.

[0089] Examples of organic groups that bond to the silicon atoms of the silanol-containing polydiorganosiloxanes described above include alkyl groups such as methyl, phenyl, and vinyl groups. From the viewpoint of ease of synthesis of polydiorganosiloxanes, the aforementioned organic groups are preferably methyl or phenyl, and more preferably methyl. Specific examples of silanol-containing polydiorganosiloxanes include polydimethylsiloxanes with one end capped by a silanol group and the other end capped by a trimethylsilyl group, polydimethylsiloxanes with both ends capped by silanol groups, and polymethylphenylsiloxanes with both ends capped by silanol groups.

[0090] There are no particular restrictions on the content of organosilicon compounds in the surface lubricating layer, as long as it meets the ranges of the water contact angles θ1 and θ2 (preferably also the water contact angle θ3).

[0091] The mass ratio of the organosilicon compound to the block copolymer in the surface lubricating layer (organosilicon compound:block copolymer) is preferably 0.1 to 1:1. That is, the surface lubricating layer preferably contains organosilicon compound and block copolymer in a mass ratio of 0.1 to 1:1 (organosilicon compound:block copolymer). Furthermore, the mass ratio of organosilicon compound to 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 less than 0.8:1. By setting the mass ratio of organosilicon compound to block copolymer in the surface lubricating layer within the above range, the water contact angles θ1 and θ2 of the surface lubricating layer can be easily controlled within the specified range. In addition, the water contact angle θ3 can be made within the above preferred range. Furthermore, since the proportion of block copolymer exposed on the surface of the surface lubricating layer can be appropriately reduced, it is easier to suppress the generation of stickiness (tackiness) during the drying process caused by the block copolymer.

[0092] It should be noted that, in this specification, the term "content of organosilicon compounds" refers to the total amount of organosilicon compounds, where the organosilicon compounds include both reactive and non-reactive organosilicon compounds. Furthermore, the aforementioned "content of organosilicon compounds" refers to the total mass of the organosilicon compound components (the total mass of the unreacted portion and the portion reacting with the block copolymer). It should also be noted that, in this specification, the content of reactive organosilicon compounds refers to the total mass of the unreacted portion and the portion reacting with the block copolymer.

[0093] When the surface lubricating layer contains reactive organosilicon as an organosilicon compound, the mass ratio of reactive organosilicon to block copolymer is not particularly limited. However, the mass ratio of reactive organosilicon to block copolymer in the surface lubricating layer (reactive organosilicon: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 setting the above mass ratio, phase separation from the block copolymer can be more effectively suppressed, and a uniform film can be easily formed. In addition, while ensuring sufficient lubricity (slipability) of the surface lubricating layer, the crosslinking of the block copolymer is sufficiently carried out without being excessive (crosslinking can be moderately promoted). Therefore, the lubricity and durability of the obtained surface lubricating layer can be fully utilized.

[0094] When the surface lubricating layer comprises reactive and non-reactive organosilicon compounds, their mass ratio is not particularly limited. The mass ratio of reactive to non-reactive organosilicon in the surface lubricating layer (reactive organosilicon:non-reactive organosilicon) is preferably 0.01 to 1:1, more preferably 0.03 to 1:1, further 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 above mass ratio, phase separation from the block copolymer is more effectively suppressed, and a uniform film is easily formed. Furthermore, while ensuring sufficient lubricity (slipability) of the surface lubricating layer, the crosslinking of the block copolymer is sufficiently carried out without over-crosslinking (crosslinking is moderately promoted). Therefore, the lubricity and durability of the obtained surface lubricating layer can be fully utilized.

[0095] (Other ingredients) In addition to block copolymers and silicone compounds, the surface lubricating layer may also contain other components. There are no particular restrictions on these other components; for example, they can be appropriately selected depending on the intended use of the medical device.

[0096] (Average tension (sliding resistance value)) From the viewpoint of obtaining excellent surface lubricity and suppressing stickiness (tackiness) during the drying process after wetting, the average tension of the surface lubricating layer of the medical device of the present invention during 40 sliding cycles in the drying process after wetting is preferably less than 550 gf, more preferably less than 500 gf, even more preferably less than 400 gf, and particularly preferably less than 300 gf. On the other hand, there is no particular limitation on the lower limit, which is about 100 gf. It should be noted that the specific method for measuring the above-mentioned average tension is the method described in the section on "Evaluation of sliding resistance during the drying process after wetting" in the examples.

[0097] Furthermore, from the viewpoint of ensuring good operability during surgery, the average tension of the surface lubricating layer of the medical instrument of the present invention during 40 sliding cycles when wet is preferably 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 less than 40 gf. On the other hand, there is no particular limitation on the lower limit, which is about 10 gf. It should be noted that the specific method for measuring the above-mentioned average tension adopts the method described in the section on "Evaluation of Sliding Resistance in Wet State" in the examples.

[0098] [Manufacturing methods for medical devices] Regarding the surface lubricating layer of the aforementioned medical device, it can be formed by any method as long as a film containing block copolymers and organosilicon compounds can be formed on the substrate layer. It is preferred to form it by applying a coating liquid containing block copolymers, organosilicon compounds and solvents onto the substrate layer.

[0099] Therefore, other aspects of the present invention provide a method for manufacturing a medical device, wherein the medical device comprises a substrate layer and a surface lubricating layer supported on at least a portion of the substrate layer, and the manufacturing method includes: preparing a coating liquid comprising a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, an organosilicon compound, and a solvent, and coating the coating liquid onto the substrate layer. Hereinafter, the method for manufacturing a medical device having the above-described structure will also be referred to as "the manufacturing method of the present invention" or "manufacturing method".

[0100] The method for manufacturing the medical device according to the present invention includes: preparing a coating liquid comprising a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, an organosilicon compound, and a solvent ((I) preparation step); and coating the coating liquid onto a substrate layer ((II) coating step). In this way, by using a solution comprising a block copolymer and an organosilicon compound as the coating liquid, a medical device having a surface lubricating layer that maintains excellent lubricity even during the drying process after wetting can be obtained.

[0101] The medical device manufactured by the method of the present invention has a structure in which the surface lubricating layer is supported on the substrate layer by applying a coating liquid comprising a block copolymer and an organosilicon compound to form the surface lubricating layer. In the coating liquid, the block copolymer and the organosilicon compound are dissolved in a solvent (the block copolymer and the organosilicon compound are uniformly mixed in the coating liquid). Therefore, the block copolymer and the organosilicon compound do not form a phase separation structure, and a uniform surface lubricating layer can be formed.

[0102] Therefore, the surface lubricating layer of the medical device manufactured by the above manufacturing method can easily control the water contact angle θ1 to be above 104° and the water contact angle θ2 to be below 102°. Furthermore, a water contact angle θ3 greater than 102° can be easily achieved. Moreover, according to the above manufacturing method, the water contact angles θ1, θ2, and θ3 described in the [medical device] section can be easily controlled within preferred ranges.

[0103] It should be noted that in the manufacturing method of the medical device involved in this invention, the terms such as water contact angles θ1, θ2 and θ3, block copolymers, and organosilicon compounds are the same as those described in the above-mentioned [medical device] section, and therefore are omitted here.

[0104] In the method for manufacturing the medical device according to the present invention, after step (II) described above, further steps such as drying and / or heat treatment ((III) drying / heat treatment step) and cleaning ((IV) cleaning step) may be performed as needed. Among these, after step (II) described above, it is preferable to further perform at least step (III) drying / heat treatment step. Hereinafter, each of the above steps (I) to (IV) will be described.

[0105] (I) Preparation process In this process, a coating solution comprising a block copolymer, a silicone compound, and a solvent is prepared. Here, in this process, the coating solution can be prepared by mixing the block copolymer, the silicone compound, and the solvent. Alternatively, a coating solution comprising a block copolymer, a silicone compound, and a solvent can be purchased and used.

[0106] The following describes in detail a preferred method for preparing a coating liquid by mixing a block copolymer, an organosilicon compound, and a solvent.

[0107] (Preparation of coating solution) The coating liquid is prepared using the block copolymer, organosilicon compound, and solvent described above. There are no particular restrictions on the order or method of adding the block copolymer, organosilicon compound, and solvent. The components can be added all at once or separately, in stages or continuously.

[0108] Furthermore, there are no particular restrictions on the mixing method of the components, and known methods can be used. Methods for preparing the coating liquid include sequentially adding an organosilicon compound and a block copolymer to a solvent, sequentially adding a block copolymer and an organosilicon compound to a solvent, or adding an organosilicon compound and a block copolymer to a solvent all at once.

[0109] From the viewpoint of easily preparing a uniform solution (coating liquid), it is preferable to add the organosilicon compound and the block copolymer sequentially to the solvent. If necessary, this addition can be carried out while stirring. More specifically, it is preferable to further mix the block copolymer after obtaining a solution of the organosilicon compound by mixing the solvent with the organosilicon compound (preferably the organosilicon compound). By adopting this configuration, it is less likely to form a phase separation structure between the block copolymer and the organosilicon compound, thus enabling the formation of a more uniform surface lubricating layer. As a result, the generation of stickiness (tackiness) during the drying process after wetting can be further suppressed.

[0110] The solvent used in the preparation of the coating solution is not particularly limited as long as it can dissolve the block copolymer, organosilicon compound (and other components if other components are used), and can be appropriately selected according to the type of block copolymer, organosilicon compound (and other components if other components are used). Specific examples of solvents for coating solutions include: alcohol solvents such as methanol, ethanol, isopropanol, butanol, and ethylene glycol; ketone solvents such as acetone, methyl ethyl ketone, and cyclohexanone; ester solvents such as ethyl acetate and butyl acetate; ether solvents such as tetrahydrofuran (THF), butyl ether, and dioxane; aliphatic hydrocarbon solvents such as hexane and heptane; aromatic hydrocarbon solvents such as benzene and toluene; and dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF). They can be used individually or in mixtures of two or more (in the form of a mixed solvent).

[0111] From the viewpoint of excellent solubility for block copolymers and organosilicon compounds (especially reactive organosilicones), the solvent preferably comprises at least one selected from the group consisting of methanol, ethanol, isopropanol, 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 at least one selected from the group consisting of acetone, methyl ethyl ketone, cyclohexanone; tetrahydrofuran, butyl ether, and dioxane, even more preferably acetone and / or tetrahydrofuran, and particularly preferably tetrahydrofuran.

[0112] The concentration of the block copolymer in the coating solution is not particularly limited. From the viewpoint of further improving coatability, lubricity, and durability of the surface lubricating 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 obtained surface lubricating layer can be fully utilized. Furthermore, it is preferable from the perspective of operability (e.g., ease of coating) and production efficiency that a uniform surface lubricating layer of the desired thickness can be easily obtained in a single coating and the viscosity of the solution is within an appropriate range. However, even outside the above range, as long as it does not affect the effect of the present invention, it can be fully utilized.

[0113] The concentration of the silicone compound in the coating solution is not particularly limited as long as it satisfies the aforementioned water contact angles θ1 and θ2 (preferably also satisfying the water contact angle θ3). From this perspective, the concentration of the silicone compound in the coating solution 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 but less than 5% by mass. If the concentration of the silicone compound is within the above range, stickiness (tackiness) during the drying process after wetting can be effectively suppressed. However, even outside the above range, as long as it does not affect the effectiveness of the present invention, it can be fully utilized.

[0114] Furthermore, the preferred mixing ratio (mass ratio) of the block copolymer and the organosilicon compound in the coating solution is the same as the preferred content ratio (mass ratio) of the block copolymer and the organosilicon compound present in the surface lubricating layer. If the mass ratio of the block copolymer and the organosilicon compound in the coating solution is within the above-mentioned range, it is easy to control the water contact angles θ1 and θ2 of the surface lubricating layer within the specified range. In addition, the water contact angle θ3 can be made within the above-mentioned preferred range. Furthermore, the durability and lubricity of the surface lubricating layer can be fully utilized. In addition, when a reactive organosilicon is used as the organosilicon compound, the preferred mixing ratio (mass ratio) of the reactive organosilicon and the block copolymer in the coating solution is the same as the preferred mass ratio of the reactive organosilicon and the block copolymer in the surface lubricating layer.

[0115] Furthermore, when using reactive and non-reactive organosilicones as organosilicon compounds, the preferred mixing ratio (mass ratio) of reactive and non-reactive organosilicones in the coating solution is the same as the preferred mass ratio of reactive and non-reactive organosilicones in the surface lubricating layer. If the mass ratio of reactive and non-reactive organosilicones in the coating solution is within the above range, the lubricity (slipability) of the surface lubricating layer is sufficiently ensured while the crosslinking of the block copolymer is sufficiently carried out without over-crosslinking (crosslinking can be moderately promoted). Therefore, the lubricity and durability of the obtained surface lubricating layer can be fully utilized.

[0116] (II) Coating process In this process, the coating liquid prepared in the above (I) preparation process is applied to the substrate layer to form a coating film (coating layer) on the substrate layer.

[0117] The substrate layer can be made of any material, such as metals, polymers, and ceramics. Specific examples of these materials are the same as those described in the section on <Substrate Layer (Substrate)> above, so detailed descriptions are omitted here.

[0118] There are no particular limitations on the method of applying the coating liquid to the surface of the substrate layer. Known methods can be used, such as coating / printing, dipping, spraying, spin coating, sponge coating with mixed solution impregnation, rod coating, mold coating, reverse coating, comma coating, gravure coating, and doctor blade coating. Among these, dipping is preferred.

[0119] It should be noted that when forming a surface lubricating layer on the narrow inner surface of catheters, guidewires, injection needles, etc., the substrate layer can be immersed in the coating solution, and degassing can be performed by depressurizing the system. By depressurizing to degas the system, the solution can quickly penetrate to the narrow inner surface, promoting the formation of the surface lubricating layer.

[0120] In addition, if a surface lubricating layer is formed only on a portion of the substrate layer, the surface lubricating layer can be formed on the desired surface portion of the substrate layer by immersing only a portion of the substrate layer in the coating liquid and applying the coating liquid to that portion of the substrate layer.

[0121] In cases where it is difficult to immerse only a portion of the substrate layer in the coating liquid, the surface portion of the substrate layer for which a surface lubricating layer is not required can be protected beforehand with a suitable removable (installable / removable) component or material (such as a coating). Then, the substrate layer is immersed in the coating liquid, the coating liquid is applied to the substrate layer, the protective component (material) for the surface portion of the substrate layer for which a surface lubricating layer is not required is removed, and the substrate layer is then reacted by heat treatment or the like, thereby forming a surface lubricating layer on the desired surface portion of the substrate layer. However, in this invention, the surface lubricating layer can be formed appropriately using conventionally known methods without any limitation to these forming methods. For example, in cases where it is difficult to immerse only a portion of the substrate layer in the coating liquid, other coating methods can be applied instead of the immersion method (e.g., methods for applying coating liquid to a specified surface portion of a medical device using a spraying device, bar coater, die coater, reverse coater, comma coater, gravure coater, spray coater, doctor blade, etc.). It should be noted that, in the case of medical devices where both the outer and inner surfaces of the cylindrical device need to have a surface lubrication layer, from the viewpoint of being able to coat both the outer and inner surfaces in one go, the dipping method is preferred.

[0122] The coating amount of the coating liquid is preferably such that the thickness (dry film thickness) of the resulting film (surface lubricating layer) is 0.1 to 10 μm, more preferably 0.3 to 5 μm, and even more preferably 0.5 to 3 μm. If the coating amount results in a film (surface lubricating layer) thickness of 0.1 μm or more, sufficient durability of the resulting film (surface lubricating layer) can be achieved. Furthermore, if the coating amount results in a film (surface lubricating layer) thickness of 10 μm or less, the surface of the film (surface lubricating layer) becomes less sticky, making manufacturing operations easier.

[0123] (III) Drying / Heat Treatment Process In the manufacturing method of the medical device of the present invention, if necessary, it is preferable to perform a heat treatment step after coating the coating liquid onto the substrate layer to form a coating film (coating layer) in the coating step (II) above. By performing the heat treatment step, not only is it easier to remove the solvent, but a more robust surface lubricating layer can also be formed. In addition, it is easier to control the water contact angles θ1 and θ2 (and water contact angle θ3).

[0124] Regarding the conditions for heat treatment, there are no particular limitations as long as it is possible to form a surface lubricating layer on the substrate layer that includes block copolymers and organosilicon compounds and satisfies the above-mentioned water contact angles θ1 and θ2 (preferably also satisfying the water contact angle θ3).

[0125] The temperature for heat treatment is not particularly limited, but is preferably 50–200°C, more preferably 100–180°C. By maintaining this temperature (performing the heat treatment), the water contact angles θ1 and θ2 (and water contact angle θ3) of the formed surface lubricating layer can be easily controlled within a specified range. Furthermore, by maintaining this temperature, a robust coating layer (surface lubricating layer) is formed. It should be noted that the temperature can be changed midway through the heat treatment.

[0126] Furthermore, there is no particular limitation on the heat treatment time, which is preferably 15 minutes to 20 hours, and more preferably 30 minutes to 12 hours. By setting such a time, it is easy to control the water contact angles θ1 and θ2 (and water contact angle θ3) of the formed surface lubricating layer within a specified range. In addition, since the crosslinking reaction in the block copolymer is effectively promoted and a strong coating layer (surface lubricating layer) is formed, high lubricity (surface lubricity) can be maintained for a longer period of time.

[0127] A drying step can also be performed before the aforementioned heat treatment step. During the drying step, the solvent is removed to some extent, allowing the subsequent heat treatment step to be performed more efficiently. The temperature of the drying step is not particularly limited, but it is preferably performed at a temperature above 10°C and below 50°C, more preferably at 20–30°C. Furthermore, the drying time is not particularly limited, but is preferably 15 minutes to 20 hours, more preferably 30 minutes to 12 hours. Additionally, the pressure conditions during drying are not limited; it can be performed at atmospheric pressure, or under pressure or depressurization.

[0128] As a means (apparatus) for carrying out the above-mentioned heat treatment and drying processes, an oven or a vacuum dryer can be used, but in the case of natural drying, no special drying means (apparatus) is required.

[0129] <Uses of Medical Devices> As a medical device involved in this invention, examples include instruments that come into contact with bodily fluids, blood, etc. Such instruments possess lubricating properties on their surface in aqueous liquids such as bodily fluids and saline solution, thereby improving operability and reducing damage to tissues and mucous membranes. Specifically, examples of medical devices involved in this invention include catheters, guidewires, and indwelling needles used within blood vessels, but are not limited to these.

[0130] Example The effects of the present invention are illustrated using the following examples and comparative examples. However, the technical scope of the present invention is not limited to the following examples. It should be noted that, unless otherwise specified, the operation in the following examples is carried out at room temperature (25°C). In addition, unless otherwise specified, "%" and "parts" refer to "mass %" and "parts by mass," respectively.

[0131] Synthesis example 1 The following reaction is carried out to produce block copolymers (1).

[0132] [Chemical Formula 1] 29.7 g of triethylene glycol was added dropwise to 72.3 g of adipic acid chloride at 50 °C, and hydrochloric acid was removed under reduced pressure at 50 °C for 3 hours to obtain a low-polyester. Next, 4.5 g of methyl ethyl ketone was added to 22.5 g of the obtained low-polyester, and this mixture was then added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of dioctyl phosphate as a surfactant, and 120 g of water. The reaction was carried out at -5 °C for 20 minutes. The resulting product was repeatedly washed with water and methanol, and then dried to obtain a polyperoxide (PPO) with multiple peroxy groups within the molecule.

[0133] Next, 0.5 g of PPO, 9.5 g of glycidyl methacrylate (GMA), and 30 g of benzene as a solvent were stirred at 80 °C under reduced pressure for 2 hours and polymerized. The polymerized reactants were then reprecipitated with diethyl ether to obtain polyglycidyl methacrylate (PPO-GMA) with multiple peroxy groups in the molecule.

[0134] Next, 1.0 g of the obtained PPO-GMA (equivalent to 7 mmol of GMA) was added to 9.0 g of N,N-dimethylacrylamide (DMAA) and 90 g of dimethyl sulfoxide as a solvent, and the reaction was carried out at 80 °C for 18 hours. The reactants were then reprecipitated with hexane and recovered to obtain a block copolymer (1) containing intramolecular epoxy groups and exhibiting lubricity when wet (structural unit (A): structural unit (B) = GMA: DMAA = 1:14 (molar ratio)). The block copolymer (1) obtained in this manner was further analyzed by... 1 Analysis by H-NMR and ATR-IR confirmed the presence of epoxy groups within the molecule. In addition, the weight-average molecular weight (Mw) of the block copolymer (1) was approximately 1.5 million, as determined by gel permeation chromatography (GPC, polystyrene equivalent).

[0135] Example 1 An amino-containing organosilicon (1) (manufactured by Shin-Etsu Chemical Industry Co., Ltd., KF-859, functional group equivalent: 6,000 g / mol, reactive organosilicon (1)) was dissolved in tetrahydrofuran (THF) (solution (1)) to a final concentration of 2.0% by mass in the coating solution. In the above solution (1), the block copolymer (1) synthesized in the above synthesis example 1 was added and dissolved to a final concentration of 5.0% by mass in the coating solution to prepare the coating solution (1).

[0136] A SUS304 grinding rod (manufactured by MISUMI Co., Ltd., RGOS3-200, outer diameter: 3.00 mm) was immersed in the above coating solution (1) and pulled at a pulling speed of 8 mm / min. THF was removed by drying at room temperature (25°C) for 1 hour to form a coating film (1) on the surface of the rod (rod (1)). Then, the rod (1) was kept in an oven at 130°C for 1 hour to heat-treat the coating film (1) (rod (1')). The rod (1') was cooled to room temperature (25°C) to prepare a sample (coated rod) (1) with a coating layer (surface lubricating layer) (dry film thickness: 1 μm) on the surface of the rod containing a block copolymer (1) and an amino-containing organosilicon (1) (containing reactants).

[0137] Example 2 In Example 1, the final concentration of amino-containing organosilicon (1) in the coating solution was changed to 4.0% by mass to prepare coating solution (2), and coating film (2) was formed using coating solution (2). Otherwise, sample (coated rod) (2) was made in the same manner as in Example 1.

[0138] Example 3 In Example 1, instead of an amino-containing organosilicon (1), an organosilicon compound (2) prepared as described below was used to prepare a coating liquid (3), and a coating film (3) was formed using the coating liquid (3). Otherwise, a sample (coated rod) (3) was prepared in the same manner as in Example 1: First, polydimethylsiloxane (Merck, number average molecular weight: 2,500, reactive organosilicon (2)) with 3-aminopropyl groups at both ends, polydimethylsiloxane (Merck, number average molecular weight: 800, reactive organosilicon (3)) with glycidyl ether groups at both ends, and dimethyl silicone oil (Shin-Etsu Chemical Industry Co., Ltd., KF-96, non-reactive organosilicon) were mixed in a mass ratio of 35:5:60 (reactive organosilicon (2): reactive organosilicon (3): non-reactive organosilicon) and the resulting mixture was taken as organosilicon compound (2).

[0139] The organosilicon compound (2) was dissolved in tetrahydrofuran (THF) to a concentration of 30% by mass. Next, the organosilicon compound (2) was diluted with tetrahydrofuran (THF) to a final concentration of 0.57% by mass (solution (3)). In the solution (3), the block copolymer (1) synthesized in the above synthesis example 1 was added and dissolved to a final concentration of 5.0% by mass in the coating liquid to prepare the coating liquid (3).

[0140] Example 4 In Example 3, the final concentration of the organosilicon compound (2) in the coating solution was changed to 1.1% by mass to prepare the coating solution (4), and the coating film (4) was formed using the coating solution (4). Otherwise, the sample (coated rod) (4) was made in the same manner as in Example 3.

[0141] Comparative Example 1 The block copolymer (1) synthesized in the above synthesis example 1 was dissolved in tetrahydrofuran (THF) to prepare a comparative coating solution (1) with a final concentration of 5.0% by mass in the coating solution.

[0142] A SUS304 grinding rod (manufactured by MISUMI Co., Ltd., RGOS3-200, outer diameter: 3.00 mm) was immersed in the above-mentioned comparative coating solution (1) and pulled at a pulling speed of 8 mm / min. THF was removed by drying at room temperature (25°C) for 1 hour to form a comparative coating film (1) on the surface of the rod (comparative rod (1)). Then, the comparative rod (1) was kept in an oven at 130°C for 1 hour to heat-treat the comparative coating film (1) (comparative rod (1')). The comparative rod (1') was cooled to room temperature (25°C) to prepare a sample (comparative coated rod) (1) with a coating layer (surface lubrication layer) containing block copolymer (1) on the surface of the rod.

[0143] Comparative Example 2 A comparative coating solution (2) was prepared by dissolving an amino-containing organosilicon (1) (manufactured by Shin-Etsu Chemical Industry Co., Ltd., KF-859, functional group equivalent: 6,000 g / mol) in tetrahydrofuran (THF) to a final concentration of 4.0% by mass in the coating solution.

[0144] A SUS304 grinding rod (manufactured by MISUMI Co., Ltd., RGOS3-200, outer diameter: 3.00 mm) was immersed in the above-mentioned comparative coating solution (2) and pulled at a speed of 8 mm / min. THF was removed by drying at room temperature (25°C) for 1 hour to form a comparative coating film (2) on the surface of the rod (comparative rod (2)). Then, the comparative rod (2) was kept in an oven at 130°C for 1 hour to heat-treat the comparative coating film (2) (comparative rod (2)). The comparative rod (2) was cooled to room temperature (25°C) to prepare a sample (comparative coated rod) with a coating layer (surface lubricating layer) containing an amino-containing organosilicon (1) on the surface of the rod (dry film thickness: 1 μm).

[0145] Comparative Example 3 In Comparative Example 2, instead of an amino-containing organosilicon (1), an organosilicon compound (2) obtained in the same manner as in Example 3 was used to prepare a comparative coating liquid (3), and a comparative coating film (3) was formed using the comparative coating liquid (3). Otherwise, a sample (comparative coated rod) (3) was prepared in the same manner as in Comparative Example 2.

[0146] [Determination of contact angle] Using the coating solutions (1) to (4) prepared in Examples 1 to 4 above, and the comparative coating solutions (1) to (3) prepared in Comparative Examples 1 to 3 above, a coating layer (surface lubrication layer) was formed in the same manner as the preparation steps of each of the above rods, and the contact angles (θ1, θ2 and θ3) of the surface lubrication layer were measured respectively according to the following method: After stirring the coating solution for 1 hour using a stirrer, the surface-polished SUS304 plate was immersed in the coating solution and pulled up at a speed of 8 mm / min. The THF was removed by drying at room temperature (25°C) for 1 hour to form a coating film. Next, the SUS plate with the coating film was kept in an oven at 130°C for 1 hour to heat-treat the coating film. Then, the SUS plate with the coating film was cooled to room temperature (25°C) to obtain samples (plates (1) to (4) and comparison plates (1) to (3)) for contact angle measurement with a coating layer (surface lubrication layer) on the plate surface.

[0147] Purified water was filled into the dedicated syringe of the contact angle measuring device (manufactured by ASUMI GIKEN, Limited, device name: B100), and a 25G syringe needle was installed. The syringe was then attached to the contact angle measuring device, and the sample obtained in the previous steps was placed on the dial. At this point, the syringe discharge was adjusted to a 1.0 μL droplet size using the image analysis function (dangling drop method). The dial was then raised to bring the sample surface into contact with the droplet, and then lowered to transfer the droplet from the syringe needle onto the sample. The contact angle (contact angle at the specified time point) was measured using the tangent method, with the elapsed time at the point when the droplet reached the sample as the baseline (0 seconds). It should be noted that 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)". In addition, the mass ratio of organosilicon compound to block copolymer (organosilicon compound:block copolymer) is represented as "organosilicon compound / block copolymer mass ratio".

[0148] [Table 1] [Evaluation of sliding resistance during the drying process after wetting] 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, the mean tension (slippage during the drying process after wetting) was evaluated according to the following method.

[0149] Reference Figure 6 and Figure 7 The test apparatus 100 used for evaluating the sliding resistance (sliding test) of the medical device 10 according to this embodiment will be described. Figure 6 A schematic diagram of the test apparatus 100 used for performing a sliding test of the medical device 10 according to this embodiment is shown, and a diagram showing the case where a pair of abutting parts 91, 92 are clamped into the medical device 10 is shown. Figure 7 A schematic diagram of the test apparatus 100 used for performing a sliding test on the medical device 10 according to this embodiment is shown, and a diagram showing the case where the medical device 10 is separated from a pair of abutting parts 91, 92 is shown.

[0150] like Figure 6 , Figure 7As shown, the testing apparatus 100 has a pair of abutting parts 91 and 92. The pair of abutting parts 91 and 92 are configured to be able to approach and separate from each other, and when the pair of abutting parts 91 and 92 are close together, the medical device 10 can be clamped with a specified force. As the testing apparatus 100, the DL1000 manufactured by Oakriver Technology Co., Ltd. can be used.

[0151] Next, the method for measuring the sliding resistance (average tension) of the sample (rod) 10' of the medical device 10 using the test apparatus 100 will be described.

[0152] First, each sample (bar) 10' is immersed in tap water for 5 minutes. Then, the sample 10' is removed from the water and placed in the clamping test machine (manufactured by Oakriver Technology, DL1000) of the test apparatus 100. A pair of abutting parts 91 and 92 are brought close to each other, and the sample 10' is clamped with a clamping force of 500 gf. At this time, the clamping pads for the abutting parts 91 and 92 are made of Shore A60 silicone and have a thickness of 12.35 mm.

[0153] Next, the sample 10' is pulled up at a specified speed and the resistance value is measured. At this time, the speed at which the sample 10' is pulled up (test speed) is set to 8.3 mm / s, and the test stroke (pulling distance) is set to 25 mm.

[0154] Then, the pair of abutting parts 91 and 92 are separated from each other, and the state of clamping the sample 10' is released, so that the sample 10' returns to the initial position.

[0155] Repeat the above process a specified number of times, measuring only the average tension (sliding resistance value) after the specified number of measurements. In this case, set the number of measurements (sliding cycles) to 40, and measure the average tension to obtain the following result: Figure 3 The results are shown.

[0156] In such Figure 3 In the sample of Comparative Example 1, large peaks were observed at approximately 15 and 35 sliding cycles, particularly around 35 cycles, where the average tension value showed a very high value of approximately 600 gf. Furthermore, in the sample of Comparative Example 2, the average tension value showed a very large value greater than 800 gf from the first sliding cycle. Additionally, in the sample of Comparative Example 3, large peaks were observed at approximately 18 and 27 sliding cycles, and after 27 cycles, the average tension value also showed a result greater than approximately 600 gf.

[0157] Furthermore, it is speculated that the stickiness of medical devices with lubricating coatings during use is caused by a sharp increase in average tension (showing a distinct peak) and a very high average tension, particularly a sharp increase in average tension. However, in the samples of Examples 1-4, no such distinct peak was observed, with the overall average tension value being less than 500 gf. That is, it can be considered that in the samples of Examples 1-4, the stickiness during the transition from a wet to a dry state was effectively suppressed.

[0158] [Evaluation of sliding resistance under dry conditions] 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, the average tension (sliding property in the dry state) was evaluated according to the following method. It should be noted that in this evaluation, the samples were not allowed to come into contact with water before the test, and the number of sliding times was not changed. Otherwise, the same operation as in the above [evaluation of sliding resistance during the drying process after wetting] was performed.

[0159] Specifically, each sample was placed in a clamping tester (OAKRIVER TECHNOLOGY, DL1000) without contact with water, and subjected to 10 sliding cycles at a clamping force of 500 gf, a test speed of 8.3 mm / s, and a test stroke of 25 mm (the clamping pad used was the same as that described above in [Evaluation of Sliding Resistance During the Drying Process After Wetting]). Sliding performance was evaluated by measuring the average tension during the 10 sliding cycles. The results are presented below. Figure 4 And Table 2.

[0160] [Evaluation of sliding resistance under wet conditions] 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, the average tension (sliding property in a wet state) was evaluated according to the following method. It should be noted that in this evaluation, the test was conducted with the sample immersed in water, and otherwise, the same operation as described above [evaluation of sliding resistance during the drying process after wetting] was performed.

[0161] Specifically, each sample was placed in a clamping tester (OAKRIVER TECHNOLOGY, DL1000) while immersed in tap water, and subjected to 40 sliding cycles at a clamping force of 500 gf, a test speed of 8.3 mm / s, and a test stroke of 25 mm (the clamping pad used was the same as the one described above in [Evaluation of Sliding Resistance During the Drying Process After Wetting]). Sliding performance was evaluated by measuring the average tension during the 40 sliding cycles. The results are presented below. Figure 5 And Table 2.

[0162] It should be noted that, in either the dry or wet state, the lower the average tension, the better the sliding performance.

[0163] [Table 2] Generally, hydrophilic block copolymers slide more easily than organosilicon compounds in a wet state. That is, hydrophilic block copolymers exhibit good sliding properties, while organosilicon compounds show reduced sliding properties. Therefore, it is appropriate to compare Comparative Examples 2 and 3, which use only organosilicon compounds, with the Examples in a wet state. Specifically, as Figure 5 As shown, when only silicone compounds are used to form the coating layer (surface lubrication layer) (Comparative Examples 2 and 3), the maximum average tension measured in the wet state is greater than 200 gf. In contrast, when reactive silicone and hydrophilic block copolymers are used to form the coating layer (surface lubrication layer) (Examples 1-4), the average tension is less than 200 gf between the 1st and 40th sliding cycles, showing good sliding performance. Furthermore, when non-reactive silicone (using reactive silicone, non-reactive silicone, and hydrophilic block copolymers) is used in addition to reactive silicone and hydrophilic block copolymers to form the coating layer (surface lubrication layer) (Examples 3 and 4), the average tension is approximately the same as or less than that of the coating layer formed using only hydrophilic block copolymers (Comparative Example 1) (i.e., exhibiting superior sliding performance).

[0164] Conversely, in the dry state, there are silicone compounds exhibiting very low sliding resistance values ​​(average tension), and generally, silicone compounds tend to slide more easily than hydrophilic block copolymers. Therefore, it is appropriate to compare Comparative Example 1, which uses only hydrophilic block copolymers, with the examples in the dry state. Specifically, as Figure 4 As shown, when only a hydrophilic block copolymer is used to form the coating layer (surface lubrication layer) (Comparative Example 1), the maximum average tension measured in the dry state is about 700 gf. In contrast, when a reactive silicone and a hydrophilic block copolymer are used to form the coating layer (surface lubrication layer) (Examples 1-4), the average tension is about 600 gf or less, showing good sliding properties.

[0165] In summary, in a moist state ( Figure 5 The results showed that the coatings (surface lubrication layers) formed using only organosilicon compounds (Comparative Examples 2 and 3) had extremely high average tension and poor sliding properties. Based on these results, it was predicted that the inclusion of organosilicon compounds in the coatings (surface lubrication layers) would lead to reduced sliding properties, but according to Table 2 above... Figure 5It is evident that even though the coating (surface lubrication layer) contains organosilicon compounds, the samples of Examples 1-4 exhibited the same excellent sliding properties as the coating (surface lubrication layer) formed using only hydrophilic block copolymers (Comparative Example 1).

[0166] In addition, according to Table 2 above and Figure 4 The results showed that, in a dry state, the samples of Examples 1-4 exhibited superior sliding properties compared to the sample of Comparative Example 1, which used only a hydrophilic block copolymer to form a coating layer (surface lubrication layer). This effect is attributed to the presence of organosilicon compounds in the surface lubrication layer.

[0167] According to the present invention, once the surface (surface lubrication layer) of the medical instrument becomes wet, it does not exhibit stickiness and maintains high lubricity even during the drying process. Therefore, for example, when performing catheter-based treatments using catheters or guidewires, it is not necessary to continuously wet the surface with each operation, or the frequency of spraying saline solution can be reduced. That is, according to the present invention, since such operations that become a burden during surgery are unnecessary, or the frequency of such operations can be reduced, a medical instrument that reduces the workload during surgery can be provided.

[0168] This application is based on Japanese Patent Application No. 2023-205991, filed on December 6, 2023, the disclosure of which is incorporated herein by reference in its entirety.

[0169] Explanation of reference numerals in the attached figures 10. Medical equipment 1. Substrate layer 1a Substrate core layer 1b Substrate surface layer 2. Lubricating layer 100 Test apparatus 10' Sample (rod) 91. Abutting components 92. Abutting component.

Claims

1. A medical device comprising a substrate layer and a surface lubricating layer disposed on at least a portion of the substrate layer, wherein, The surface lubricating layer comprises a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, and an organosilicon compound. When 1.0 μL of purified water is added to the surface lubricating layer, and the water contact angle after 5 seconds of contact between the purified water droplet and the surface lubricating layer is defined as θ1, and the water contact angle after 5 minutes of contact is defined as θ2, θ1 is greater than 104° and θ2 is less than 102°.

2. The medical device as described in claim 1, wherein, When the water contact angle after one minute of contact between the purified water droplet and the surface lubricating layer is defined as θ3, The θ3 is greater than 102°.

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

1.

4. The medical device as described in claim 1 or 2, wherein, The organosilicon compound contains reactive organosilicon.

5. The medical device as described in claim 4, wherein, The reactive organosilicon has at least one selected from the group consisting of hydroxyl (-OH), carboxyl, amino (-NH2), epoxy, olefinic unsaturated group and alkoxysilyl group.

6. The medical device as described in claim 1 or 2, wherein, The epoxy-containing reactive monomer comprises at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexyl methyl acrylate, 3,4-epoxycyclohexyl methyl methacrylate, β-methyl glycidyl methacrylate, and allyl glycidyl ether.

7. The medical device as described in 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 medical devices, wherein, The medical device comprises a substrate layer and a surface lubricating layer supported on at least a portion of the substrate layer, and the manufacturing method includes: Prepare a coating solution comprising a block copolymer having structural units (A) derived from an epoxy-containing reactive monomer and structural units (B) derived from a hydrophilic monomer, an organosilicon compound, and a solvent. The coating liquid is applied to the substrate layer.

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

10. The method of claim 8 or 9, wherein, The organosilicon compound contains reactive organosilicon.

11. The method of claim 10, wherein, The reactive organosilicon has at least one selected from the group consisting of hydroxyl (-OH), carboxyl, amino (-NH2), epoxy, olefinic unsaturated group and 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, isopropanol, 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 of claim 8 or 9, wherein, The epoxy-containing reactive monomer comprises at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate, 3,4-epoxycyclohexyl methyl acrylate, 3,4-epoxycyclohexyl methyl methacrylate, β-methyl glycidyl methacrylate, and allyl glycidyl ether.

14. The method of 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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