Catheter

Abstract

Provided is a catheter excellent in surface lubricity and durability.　In this catheter, a hydrophilic coating layer is carried on at least a part of the outer surface of a base material. The number of fine particles of 10-50 μm detected by a fine particle test is 2000 or less, and the sliding resistance value measured per slide in a total of 20 slides in a pinch test is 5-20 gf.

Description

catheter

[0001] The present invention relates to a catheter having excellent surface lubricity and durability.

[0002] When performing various treatments in a biological lumen such as a blood vessel, the surgeon delivers the tip of a guiding catheter along a guide wire previously inserted into the blood vessel to a location close to a lesion (e.g., a narrowed portion formed in the blood vessel, such as an occlusion or a calcified lesion).The surgeon then advances a treatment device such as a balloon catheter from the tip of the guiding catheter to treat the lesion.

[0003] When treating a lesion using a treatment device such as a balloon catheter, a guidewire must be inserted and passed through the stenotic area as a preliminary step. However, because guidewires are generally flexible, it is difficult to pass them through the stenotic lesion.

[0004] Therefore, support catheters have been proposed that support the passage of a guidewire through a stenotic area that would be difficult to pass using a guidewire alone. The support catheter has a shape that allows the guidewire to be inserted into a cylindrical lumen, and has relatively rigidity, so that the support catheter can be passed through the lesion while integrated with the guidewire. For example, Japanese Patent Application Laid-Open No. 2018-11953 discloses a guidewire support catheter that can improve rigidity.

[0005] However, the support catheter described in JP 2018-11953 A has a certain rigidity, which may damage tissues such as blood vessels, and furthermore, it is difficult for the surgeon to operate. Therefore, the support catheter is required to have a lubricating surface, i.e., to reduce the possibility of tissue damage and further improve operability.

[0006] One possible method for providing such surface lubricity is to retain a hydrophilic substance on the outer surface of the support catheter, but this method poses another problem: when the support catheter passes through a stenotic lesion, the hydrophilic substance peels off from the catheter surface due to wear and abrasion, resulting in low durability.

[0007] The present invention has been made to solve the above-mentioned problems, and an object of the present invention is to provide a catheter that has excellent surface lubricity and also has excellent durability.

[0008] The present inventors have conducted extensive research to solve the above problems, and as a result have found that the above problems can be solved by a specific catheter having a hydrophilic coating layer, which has led to the completion of the present invention.

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

[0010] One aspect of the present invention is a catheter having a hydrophilic coating layer on at least a portion of the outer surface of a substrate, wherein the number of microparticles of 10 μm or more and less than 50 μm detected by a microparticle test is 2,000 or less, and the sliding resistance value measured in a pinch test over 20 sliding cycles is 5 gf or more and 20 gf or less for each cycle.

[0011] 2. In the catheter described in 1 above, it is preferable that the outer diameter of the tip portion of the base material is 0.3 mm to 0.9 mm, and the outer diameter of the shaft portion is 0.4 mm to 1 mm.

[0012] 3. In the catheter described in 1. or 2. above, it is preferable that the inner diameter of the tip portion of the base material is 0.1 mm to 0.6 mm, and the inner diameter of the shaft portion is 0.2 mm to 0.7 mm.

[0013] 4. In the catheter described in any one of 1. to 3. above, it is preferable that, in the sliding resistance values ​​measured for each of 20 sliding operations in the pinch test, the sliding resistance value for the 20th sliding operation is equal to or less than the sliding resistance value for the first sliding operation.

[0014] 5. In the catheter described in any of 1. to 4. above, when the sliding resistance value at the 20th time measured in the pinch test is X and the smallest sliding resistance value among the sliding resistance values ​​at the 1st to 19th times is Y, it is preferable that the value of {(Y−X) / X}×100(%) be −10% to 10%.

[0015] 6. The catheter according to any one of the above items 1 to 5 is preferably a guidewire support catheter.

[0016] 7. The catheter according to any one of the above items 1 to 6 is preferably used together with a guide wire having an outer diameter of 0.012 to 0.016 inches.

[0017] FIG. 1 is a schematic diagram showing a catheter according to one embodiment of the present invention. FIG. 2-1 is a photograph of the test equipment used to evaluate the number of fine particles. FIG. 2-2 is a photograph showing an enlarged portion of the test equipment used to evaluate the number of fine particles. FIG. 3 is a graph showing the results of the sliding resistance evaluation of the catheters of Example 1 and Comparative Example 1. FIG. 4 is a graph showing the results of the sliding resistance evaluation of the catheters of Comparative Example 2 and Comparative Example 3.

[0018] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. In the description of the drawings, identical elements are designated by the same reference numerals, and redundant description will be omitted. The dimensional proportions in the drawings are exaggerated for the sake of explanation and may differ from the actual proportions. The present invention is not limited to the following embodiments. Furthermore, in this specification, unless otherwise specified, operations and measurements of physical properties are performed at room temperature (20°C to 25°C) and at a relative humidity of 40% RH to 50% RH.

[0019] Furthermore, throughout this specification, singular expressions should be understood to include the plural concept unless otherwise specified. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise specified. Furthermore, terms used in this specification should be understood to be used in the sense commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the event of a conflict, this specification (including definitions) shall prevail. The present invention is not limited to the following embodiments and can be modified in various ways within the scope of the claims. Furthermore, in this specification, "X to Y" means a range including the numerical values ​​(X and Y) described before and after it as the lower and upper limits, and means "X or more and Y or less." Furthermore, concentration "%" means mass concentration "% by mass" unless otherwise specified.

[0020] A catheter according to one embodiment of the present invention is a catheter having a hydrophilic coating layer on at least a portion of the outer surface of a base material, wherein the number of microparticles of 10 μm or more and less than 50 μm detected by a microparticle test is 2,000 or less, and the sliding resistance value measured in 20 sliding cycles in a pinch test is 5 gf or more and 20 gf or less for each cycle. A catheter according to one embodiment of the present invention having such a configuration is useful because it combines excellent surface lubricity (slidability) with excellent durability.

[0021] FIG. 1 is an overall view showing a catheter 1 according to an embodiment of the present invention. In this specification, the direction in which the linear shaft portion 10 extends is defined as the axial direction. In the axial direction, the side inserted into a biological lumen is defined as the "distal side," and the proximal side (the side on which the hub 30 is located in FIG. 1) is defined as the "base side." Furthermore, for each component of the catheter 1, a portion extending from the distal end (the most distal end) in the axial direction is defined as the "distal portion 20." Furthermore, the portion of the catheter 1 according to an embodiment of the present invention that is composed of the shaft portion 10 and the distal portion 20 is referred to as the "base material 60."

[0022] 1, a catheter 1 according to one embodiment has a shaft portion 10, a tip portion 20 provided at the tip of the shaft portion, a hub (hub tube) 30 provided on the base end side of the shaft portion 10, and a hydrophilic coating layer 50 carried on the outer surface of a base material 60 over a certain range from the tip (most distal end) along the axial direction. The catheter 1 according to one embodiment may also be provided with a kink-resistant protector 40 on the tip side of the hub 30.

[0023] The base material 60, which is made up of the shaft portion 10 and the tip portion 20, is configured as a flexible tubular body. A lumen 10H is formed over the entire length of the base material 60. The lumen 10H opens at the tip of the tip portion 20.

[0024] (Tip Portion and Shaft Portion) The outer diameter of the tip portion according to one embodiment is not particularly limited, but is preferably 0.3 mm to 0.9 mm, and more preferably 0.4 mm to 0.8 mm. The outer diameter of the shaft portion according to one embodiment is not particularly limited, but is preferably 0.4 mm to 1 mm, and more preferably 0.5 mm to 0.9 mm. For example, in a catheter 1 according to one embodiment, the outer diameter of the tip portion is preferably 0.3 mm to 0.9 mm, and the outer diameter of the shaft portion is preferably 0.4 mm to 1 mm, or the outer diameter of the tip portion is preferably 0.4 mm to 0.8 mm, and the outer diameter of the shaft portion is preferably 0.5 mm to 0.9 mm. Catheters with outer diameters of the tip portion and shaft portion within the above ranges are suitable for use with guidewires and the like used in more constricted areas. Treatments in narrow blood vessels, etc., are particularly susceptible to friction, etc., but the catheter according to the present invention has excellent surface lubricity and durability, making it suitable for such treatments. The outer diameter of the shaft portion is preferably larger than the outer diameter of the tip portion. Here, the outer diameter of the tip portion is the value measured at the very tip of the catheter using a laser outer diameter measuring device. The outer diameter of the shaft portion is the value measured at the proximal portion of the catheter using a laser outer diameter measuring device. Here, the proximal portion refers to the region extending from the base end of the shaft portion to approximately 10 cm to approximately 30 cm in the axial direction.

[0025] The inner diameter of the tip portion according to one embodiment is not particularly limited, but is preferably 0.1 mm to 0.6 mm, and more preferably 0.35 mm to 0.45 mm. The inner diameter of the shaft portion according to one embodiment is not particularly limited, but is preferably 0.2 mm to 0.7 mm, and more preferably 0.4 mm to 0.55 mm. For example, in a catheter 1 according to one embodiment, the inner diameter of the tip portion is preferably 0.1 mm to 0.6 mm, and the inner diameter of the shaft portion is preferably 0.2 mm to 0.7 mm, and the inner diameter of the tip portion is preferably 0.35 mm to 0.45 mm, and the inner diameter of the shaft portion is preferably 0.4 mm to 0.55 mm. Catheters with inner diameters of the tip portion and shaft portion within the above ranges are suitable for use with guidewires and the like used in more constricted areas. While such areas are susceptible to friction and other factors, the catheter according to the present invention has excellent surface lubricity and durability, making it suitable for use in the treatment of such more constricted areas. The inner diameter of the shaft portion is preferably larger than the inner diameter of the tip portion. Here, the inner diameter of the tip portion is the diameter of a pin gauge that can be inserted into the tip of the catheter, and the inner diameter of the shaft portion is the diameter of the core wire used to form the catheter.

[0026] The length of the base material consisting of the shaft portion and the tip portion according to one embodiment can be appropriately selected depending on the application of the catheter. From the viewpoint of suitability for use in vivo, the length is preferably, for example, 50 cm to 250 cm, and more preferably 100 cm to 200 cm.

[0027] The material for the shaft and tip is not particularly limited as long as it is flexible, and various materials can be used. Specifically, the material for the base material can be a metal material, a polymer material, or a ceramic, among others, but a polymer material is preferable, and for example, the base material can be a multilayer molded material with braided metal reinforcing wires embedded along almost the entire length.

[0028] The polymeric material (resin material or elastomer material) is not particularly limited, and may be a polymeric material commonly used for catheters. Specific examples include polyamide resin, polyolefin resin such as polyethylene resin or polypropylene resin, modified polyolefin resin, cyclic polyolefin resin, epoxy resin, polyurethane resin, diallyl phthalate resin (allyl resin), polycarbonate resin, fluororesin, amino resin (urea resin, melamine resin, benzoguanamine resin), polyester resin such as polyethylene terephthalate resin or polybutylene terephthalate resin, styrene resin, acrylic resin, polyacetal resin, vinyl acetate resin, phenolic resin, vinyl chloride resin, silicone resin, polyether resin, and polyimide resin, with polyamide resin being preferred.

[0029] Thermoplastic elastomers such as polyurethane elastomers, polyester elastomers, and polyamide elastomers (nylon elastomers) can also be used as the substrate material.

[0030] These polymeric materials may be used alone, or as a mixture of two or more kinds, or as a copolymer of two or more kinds of monomers constituting any of the above-mentioned resins or elastomers. The polymeric material may be appropriately selected from those that are optimal as the base material for the intended use, such as a catheter, guide wire, or indwelling needle.

[0031] (Hub) A hub is attached (fixed) to the proximal end of the shaft. This hub has an inner cavity that communicates with the lumen. This inner cavity has an inner diameter approximately equal to the inner diameter of the lumen, is continuous with the inner surface of the proximal end of the lumen without creating a step, etc., and may have an inner surface tapered so that the diameter expands toward the proximal end opening so that a syringe or the like can be connected.

[0032] The hub can be used to insert or remove a long object (linear object) such as a guide wire, or to inject various liquids such as contrast media (X-ray contrast media), medicinal solutions, saline, etc. The hub can also be connected to other devices such as a Y-shaped branch connector.

[0033] (Hydrophilic Coating Layer) The catheter according to the present invention has a hydrophilic coating layer carried on at least a portion of the outer surface of the base material. This configuration gives the catheter according to the present invention excellent surface lubricity. Note that "carrying" refers to a state in which the hydrophilic coating layer is fixed in a state in which it does not easily separate from the outer surface, and includes not only a state in which the entire outer surface of the catheter is completely covered with the hydrophilic coating layer, but also a state in which only a portion of the outer surface of the catheter is covered with the hydrophilic coating layer, i.e., a state in which the hydrophilic coating layer is attached to only a portion of the outer surface of the catheter.

[0034] On the outer surface of the substrate (the outer surface of the catheter) according to one embodiment, the hydrophilic coating layer is preferably, but not limited to, a form that completely covers the outer surface in the circumferential direction within a certain distance in the axial direction from the tip (tip) of the substrate. In this case, the certain distance can be rephrased as the axial length of the hydrophilic coating layer.

[0035] The axial length of the hydrophilic coating layer is not particularly limited, but is preferably 10 cm to 100 cm from the tip (tip), and more preferably 20 cm to 80 cm. The axial length of the hydrophilic coating layer is also not particularly limited, but is preferably 10% to 60% of the total length of the base material, and more preferably 20% to 40%. By having the length within this range, the catheter surface will have sufficient lubricity, and the number of fine particles generated from the hydrophilic coating layer can be reduced.

[0036] The thickness of the hydrophilic coating layer according to one embodiment is preferably 0.1 μm to 10 μm, more preferably 0.3 μm to 5 μm, even more preferably 0.5 μm to 3 μm, and particularly preferably 0.7 μm to 2 μm. Having a thickness of 0.1 μm or more provides more sufficient surface lubricity. Furthermore, having a thickness of 10 μm or less makes the surface of the hydrophilic coating layer less sticky, making handling during manufacturing easier, for example. Furthermore, having a thickness of 10 μm or less provides more sufficient durability.

[0037] The hydrophilic coating layer of the catheter according to one embodiment may contain a block copolymer, wherein the block copolymer has a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer.

[0038] The reactive monomer having an epoxy group that constitutes the block copolymer has an epoxy group as a reactive group. By introducing the structural unit (A) derived from such a reactive monomer into the block copolymer, the epoxy group is ring-opened, and crosslinking (bonding) between the block copolymers progresses, thereby increasing the film strength of the hydrophilic coating layer. Furthermore, when the substrate is a resin material, the ring-opened epoxy group can also cause crosslinking (bonding) between the block copolymer and the substrate.

[0039] The reactive monomer constituting the block copolymer is not particularly limited as long as it has an epoxy group, and known compounds can be used. Among them, the reactive monomer having an epoxy group preferably includes at least one selected from the group consisting of glycidyl acrylate, glycidyl methacrylate (GMA), 3,4-epoxycyclohexylmethyl acrylate, 3,4-epoxycyclohexylmethyl methacrylate, β-methylglycidyl methacrylate, and allyl glycidyl ether, because this makes it easier to control the crosslinking or polymerization of the block copolymer.

[0040] Among these, glycidyl (meth)acrylate is more preferred, and glycidyl methacrylate is particularly preferred, in consideration of the ability to further promote the crosslinking reaction and ease of production. That is, in a more preferred embodiment of the present invention, the reactive monomer having an epoxy group is at least one of glycidyl acrylate and glycidyl methacrylate. Furthermore, in a particularly preferred embodiment of the present invention, the reactive monomer having an epoxy group is glycidyl methacrylate.

[0041] The reactive monomers may be used alone or in combination of two or more. That is, the structural unit (A) derived from the reactive monomer may be a homopolymer type composed of one type of reactive monomer alone, or a copolymer type composed of two or more types of the reactive monomers. When two or more types are used, the structural unit (A) may be in the form of a block copolymer or a random copolymer.

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

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

[0044] Among these, in consideration of the imparting of excellent lubricity, ease of synthesis, and operability, N,N-dimethylacrylamide, acrylamide, or 2-hydroxyethyl methacrylate are more preferred, and N,N-dimethylacrylamide is particularly preferred. That is, in a more preferred embodiment of the present invention, the hydrophilic monomer is at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, and 2-hydroxyethyl methacrylate. Furthermore, in a particularly preferred embodiment of the present invention, the hydrophilic monomer is N,N-dimethylacrylamide.

[0045] The hydrophilic monomers may be used alone or in combination of two or more. That is, the structural unit (B) derived from the hydrophilic monomer may be a homopolymer type composed of one hydrophilic monomer alone, or a copolymer type composed of two or more of the hydrophilic monomers. When two or more types are used, the structural unit (B) may be in the form of a block copolymer or a random copolymer.

[0046] The block copolymer has a structural unit (A) derived from the reactive monomer and a structural unit (B) derived from the hydrophilic monomer. The ratio of the structural unit (A) to the structural unit (B) is not particularly limited as long as the above-described effects are achieved. Considering good lubricity, lubrication retention, hydrophilic coating layer strength, and substrate bonding, the ratio of the structural unit (A) to the structural unit (B) (molar ratio of structural unit (A):structural unit (B)) is preferably 1:2 to 1:20, and particularly preferably 1:10 to 1:14. Within this range, the hydrophilic coating layer can exhibit sufficient lubricity due to the structural unit (B), and can exhibit sufficient hydrophilic coating layer strength, substrate bonding, and durability due to the structural unit (A). The molar ratio of the structural unit (A):structural unit (B) can be controlled by adjusting the feed ratio (molar ratio) of each monomer during the block copolymer production stage. Therefore, the charge ratio (molar ratio) of the reactive monomer having an epoxy group to the hydrophilic monomer in the production stage of the block copolymer is preferably 1:2 to 1:20, and particularly preferably 1:10 to 1:14. The molar ratio of the structural unit (A):structural unit (B) can be determined, for example, by NMR measurement ( １ H-NMR measurement, １３ This can be confirmed by performing spectroscopy (e.g., C-NMR measurement).

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

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

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

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

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

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

[0053] The weight-average molecular weight of the block copolymer is preferably 10,000 to 10,000,000 from the viewpoint of solubility. The weight-average molecular weight of the block copolymer is more preferably 100,000 to 5,000,000 from the viewpoint of ease of preparation of the coating liquid. In this specification, the "weight-average molecular weight" is a value measured by gel permeation chromatography (GPC) using polystyrene as a standard substance.

[0054] The method for producing the block copolymer is not particularly limited, and can be produced by applying conventionally known polymerization methods such as living radical polymerization, polymerization using a macroinitiator, and polycondensation. Of these, living radical polymerization or polymerization using a macroinitiator is preferred because it allows for easy control of the molecular weight and molecular weight distribution of the structural units (portions) derived from reactive monomers and the structural units (portions) derived from hydrophilic monomers. The living radical polymerization method is not particularly limited, and examples thereof include methods described in JP-A-11-263819, JP-A-2002-145971, JP-A-2006-316169, and atom transfer radical polymerization (ATRP), which can be applied in the same manner or with appropriate modifications. Furthermore, in a polymerization method using a macroinitiator, for example, a macroinitiator having a reactive moiety with a reactive functional group and a radically polymerizable group such as a peroxide group is prepared, and then the macroinitiator is polymerized with a monomer for forming a hydrophilic moiety, thereby making it possible to prepare a block copolymer having a hydrophilic moiety and a reactive moiety.

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

[0056] The hydrophilic coating layer may contain other components in addition to the block copolymer. The other components are not particularly limited and may be appropriately selected depending on, for example, the intended use of the medical device.

[0057] (Number of Particles Detected by Particle Test) In the catheter of the present invention, the number of particles of 10 μm or more and less than 50 μm detected by the particle test is 2,000 or less. Here, the number of particles of 10 μm or more and less than 50 μm means the value obtained by subtracting the number of particles of 50 μm or more from the number of particles of 10 μm or more detected by the method described in the section "Evaluation of Particle Count" in the Examples below. In other words, in the catheter of the present invention, the value obtained by subtracting the number of particles of 50 μm or more from the number of particles of 10 μm or more detected by the particle test is 2,000 or less. Note that the particles detected by the particle test are mainly particles that detach from the hydrophilic coating layer during the test. When the number of particles of 10 μm or more and less than 50 μm detected by the particle test is within the above range, the number of particles that detach from the hydrophilic coating layer is small, and it can be said that the durability of the hydrophilic coating layer and the catheter is excellent. On the other hand, if the number of fine particles having a size of 10 μm or more and less than 50 μm exceeds 2000, this is not preferable from the viewpoint of the durability of the hydrophilic coating layer and the catheter.

[0058] From the viewpoint of achieving superior durability, the catheter according to one embodiment of the present invention has a particle test in which the number of particles of 10 μm or more and less than 50 μm is detected is preferably 1,900 or less, and more preferably 1,800 or less. On the other hand, the lower limit is not particularly limited, but may be about 100 or about 10. When the number of particles of 10 μm or more and less than 50 μm detected by the particle test is within the above range, the catheter has superior durability.

[0059] In one embodiment of the catheter, the number of particles of 50 μm or larger detected by the particle test is preferably 5 or less, more preferably 3 or less, even more preferably 1 or less, and particularly preferably 0. When the number of particles of 50 μm or larger detected by the particle test is within the above range, the catheter has better durability. Here, the number of particles of 50 μm or larger can be measured by the method described in the section "Evaluation of the number of particles" in the Examples below.

[0060] In one embodiment, the catheter has a particle test that detects 2,000 or fewer particles of 10 μm or larger but less than 25 μm in size, preferably 1,900 or fewer particles, and more preferably 1,850 or fewer particles. The lower limit is not particularly limited, but may be approximately 100 or even 10 particles. Having the particle test detectable within the above range results in a catheter with superior durability. Here, the particle test number of 10 μm or larger but less than 25 μm refers to the number of particles of 10 μm or larger detected by the method described in the "Evaluation of Particle Count" section of the Examples section below minus the number of particles of 25 μm or larger.

[0061] In one embodiment, the catheter has a particle test that detects 100 or fewer particles of 25 μm or larger but less than 50 μm in size, preferably 80 or fewer, and even more preferably 60 or fewer particles. The lower limit is not particularly limited, but may be approximately 10 or even 5. By detecting a particle test that detects particles of 25 μm or larger but less than 50 μm in size within the above range, the catheter has superior durability. Here, the particle test number of 25 μm or larger but less than 50 μm refers to the number of particles of 25 μm or larger detected by the method described in the "Evaluation of particle count" section of the Examples section below minus the number of particles of 50 μm or larger.

[0062] (Sliding resistance value in pinch test) The catheter according to the present invention has a sliding resistance value of 5 gf or more and 20 gf or less for each of 20 sliding cycles measured in a pinch test. When the sliding resistance value measured for each cycle in the pinch test is within the above range, the catheter can be said to have excellent sliding properties, i.e., excellent surface lubricity. Furthermore, if the sliding resistance value exceeds 20 gf, the surface lubricity is low and the influence of friction, etc. becomes greater, which makes the hydrophilic coating layer more likely to peel off and reduces durability, which is undesirable. If the sliding resistance value is less than 5 gf, the catheter will come out due to the reaction force when the guidewire is pushed, which is undesirable.

[0063] Furthermore, the catheter according to one embodiment has a sliding resistance value of 5 gf or more for each of 20 sliding motions measured in a pinch test, preferably 6 gf or more, more preferably 7 gf or more, even more preferably 8 gf or more, particularly preferably 9 gf or more, and most preferably 10 gf or more. Furthermore, the catheter according to one embodiment has a sliding resistance value of 20 gf or less for each of 20 sliding motions measured in a pinch test, preferably 19 gf or less, more preferably 18 gf or less, even more preferably 17 gf or less, and particularly preferably 16 gf or less. That is, in a catheter according to one embodiment, the sliding resistance values ​​measured for each of 20 sliding motions in a pinch test are 5 gf or more and 19 gf or less, 5 gf or more and 18 gf or less, 5 gf or more and 17 gf or less, 5 gf or more and 16 gf or less, 6 gf or more and 20 gf or less, 6 gf or more and 19 gf or less, 6 gf or more and 18 gf or less, 6 gf or more and 17 gf or less, 6 gf or more and 16 gf or less, 7 gf or more and 20 gf or less, 7 gf or more and 19 gf or less, 7 gf or more and 18 gf or less, 7 gf or more and 17 gf or less The sliding resistance may be 7 gf or less, 7 gf or less to 16 gf, 8 gf or less to 20 gf, 8 gf or less to 19 gf, 8 gf or less to 18 gf, 8 gf or less to 17 gf, 8 gf or less to 16 gf, 9 gf or less to 20 gf, 9 gf or less to 19 gf, 9 gf or less to 18 gf, 9 gf or less to 17 gf, 9 gf or less to 16 gf, 10 gf or less to 20 gf, 10 gf or less to 19 gf, 10 gf or less to 18 gf, 10 gf or less to 17 gf, or 10 gf or less to 16 gf. When the sliding resistance value measured in each pinch test is within the above range, the catheter has better surface lubricity. The specific method for measuring the sliding resistance value in each pinch test, measured over a total of 20 sliding cycles, is the same as the method described in the "Evaluation of Sliding Resistance" section of the Examples.

[0064] Furthermore, in a catheter according to one embodiment of the present invention, it is preferable that the sliding resistance value at the 20th time is equal to or less than the sliding resistance value at the first time when the sliding resistance value is measured for a total of 20 times in a pinch test. When the sliding resistance value at the 20th time in the pinch test is equal to or less than the sliding resistance value at the first time, the catheter has better sliding properties, i.e., better surface lubricity, and can also be said to have excellent durability. Note that the specific method for measuring the sliding resistance values ​​at the first time and the 20th time in the pinch test is the method described in the section "Evaluation of sliding resistance" in the Examples.

[0065] Furthermore, from the viewpoint of obtaining superior surface lubricity and superior durability, the catheter according to one embodiment of the present invention preferably has a value of {(Y-X) / X} x 100(%) of -10% to 10%, where X is the sliding resistance value at the 20th pinch test and Y is the smallest sliding resistance value among the sliding resistance values ​​at the 1st to 19th pinch tests. Furthermore, this value is more preferably -5% to 5%, and even more preferably -3% to 3%. The specific method for measuring the sliding resistance value at the 20th pinch test (X) and the smallest sliding resistance value at the 1st to 19th pinch tests (Y) is the method described in the "Evaluation of Sliding Resistance" section of the Examples.

[0066] In addition, in order to obtain superior surface lubricity and superior durability, the catheter according to one embodiment of the present invention is preferably configured such that the absolute value of the difference between the average value of the sliding resistance measured in the pinch test over 20 times and the sliding resistance value of each time is 3 gf or less, more preferably 2.5 gf or less, and even more preferably 2 gf or less. Furthermore, the lower limit of the absolute value of the difference between the average value of the sliding resistance measured over 20 times and the sliding resistance value of each time is not particularly limited, but is preferably 0 gf. The specific method for measuring the average value of the sliding resistance measured over 20 times and the sliding resistance value of each time in the pinch test is the method described in the section "Evaluation of sliding resistance" in the Examples.

[0067] <Method for manufacturing catheter> The hydrophilic coating layer of the catheter may be formed by any method as long as it can form a coating containing a block copolymer on the outer surface of a base material consisting of a tip portion and a shaft portion. Preferably, it is formed by applying a coating liquid containing a block copolymer and a solvent onto the outer surface of the base material.

[0068] Therefore, another aspect of the present invention provides a method for manufacturing a catheter having a hydrophilic coating layer carried on at least a portion of the outer surface of a substrate, wherein the number of fine particles of 10 μm or more and less than 50 μm detected by a fine particle test is 2,000 or less, and the sliding resistance value measured in a total of 20 sliding cycles in a pinch test is 5 gf or more and 20 gf or less for each cycle. The method for manufacturing a catheter having the above configuration will be referred to hereinafter as a "manufacturing method according to one embodiment" or simply as a "manufacturing method."

[0069] A manufacturing method according to one embodiment preferably includes the steps of: preparing a coating liquid containing a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, and a solvent ((I) preparation step); applying the coating liquid to the outer surface of a substrate ((II) application step); and subjecting the substrate to which the coating liquid has been applied to a heat treatment in which the heating temperature is increased in stages ((III) heat treatment step). A catheter obtained by this manufacturing method not only has excellent lubricity, but also has durability against loads such as abrasion and abrasion.

[0070] In other words, the catheter according to one embodiment of the present invention is preferably a catheter manufactured by a manufacturing method including the steps of: preparing a coating liquid containing a block copolymer having a structural unit (A) derived from a reactive monomer having an epoxy group and a structural unit (B) derived from a hydrophilic monomer, and a solvent ((I) preparation step); applying the coating liquid onto the outer surface of a substrate ((II) application step); and performing a heat treatment on the substrate to which the coating liquid has been applied, in which the heating temperature is increased in a stepwise manner ((III) heat treatment step).

[0071] In the method for manufacturing a catheter according to one embodiment of the present invention, the terms block copolymer, base material, etc. are the same as those described in the above sections, and therefore will not be explained here.

[0072] The above steps (I) to (III) will be described below.

[0073] [(I) Preparation Step] In this step, a coating liquid containing a block copolymer and a solvent is prepared. Here, in this step, the coating liquid may be prepared by mixing the block copolymer and the solvent to prepare the coating liquid. Alternatively, a coating liquid containing the block copolymer and the solvent may be purchased and used.

[0074] A preferred embodiment of preparing a coating liquid by mixing a block copolymer and a solvent will be described in detail below.

[0075] (Preparation of Coating Liquid) A coating liquid is prepared using the block copolymer and solvent. The method for adding the block copolymer and solvent is not particularly limited. The components may be added all at once or separately, stepwise or continuously. The method for mixing the components is also not particularly limited, and known methods can be used. From the viewpoint of facilitating the preparation of a uniform solution (coating liquid), it is preferable to add the block copolymer sequentially to the solvent. The addition may be carried out while stirring, if necessary.

[0076] The solvent used to prepare the coating liquid is not particularly limited as long as it can dissolve the block copolymer (and other components, if used), and is appropriately selected depending on the type of block copolymer (and other components, if used). Specific examples of solvents for the coating liquid include alcohol-based solvents such as methanol, ethanol, isopropyl alcohol, butanol, and ethylene glycol; ketone-based solvents such as acetone, methyl ethyl ketone, and cyclohexanone; ester-based solvents such as ethyl acetate and butyl acetate; ether-based solvents such as tetrahydrofuran (THF), butyl ether, and dioxane; aliphatic hydrocarbon-based solvents such as hexane and heptane; aromatic hydrocarbon-based solvents such as benzene and toluene; dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and the like. These solvents may be used alone or in combination (in the form of a mixed solvent) of two or more types.

[0077] The concentration of the block copolymer in the coating solution is not particularly limited. From the viewpoint of further improving the coatability and the lubricity and durability of the hydrophilic coating 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. When the concentration of the block copolymer is within the above range, the lubricity and durability of the resulting hydrophilic coating layer can be fully exhibited. Furthermore, a uniform hydrophilic coating layer of the desired thickness can be easily obtained with a single coating, and the viscosity of the solution falls within an appropriate range, which is preferable in terms of operability (e.g., ease of coating) and production efficiency. However, even if the concentration is outside the above range, it can be satisfactorily used as long as it does not affect the effects of the present invention.

[0078] [(II) Coating Step] In this step, the coating liquid prepared in the above (I) Preparation Step is applied onto the outer surface of the substrate of the catheter to form a coating film (coating layer) on the outer surface of the substrate.

[0079] The method for applying (coating) the coating liquid onto the outer surface of the catheter substrate is not particularly limited, and any conventionally known method can be used, such as coating / printing, immersion (dipping, dip coating), spraying, spin coating, mixed solution-impregnated sponge coating, bar coating, die coating, reverse coating, comma coating, gravure coating, doctor knife, etc. Of these, the immersion method (dipping, dip coating) is preferred.

[0080] When the immersion method is used, the rate at which the catheter substrate is immersed in the coating liquid and then pulled up is not particularly limited, but is preferably 5 mm / min to 30 mm / min, more preferably 10 mm / min to 25 mm / min, and even more preferably 10 mm / min to 20 mm / min. By keeping the pulling rate within the above range, a desired amount of coating liquid can be applied to the outer surface of the catheter substrate.

[0081] Furthermore, when forming a hydrophilic coating layer only on a portion of the outer surface of the catheter substrate, the hydrophilic coating layer can be formed on the desired surface portion of the outer surface of the catheter by immersing only a portion of the substrate in the coating liquid and coating the coating liquid onto a portion of the outer surface of the catheter.

[0082] When forming a hydrophilic coating layer only on a portion of the outer surface of the catheter substrate, it is preferable to immerse the substrate from the distal end (i.e., from the distal end) in the coating solution, and then immerse a certain range from the distal end to the shaft in the coating solution, thereby completely covering the outer surface of the substrate within a certain axial distance from the distal end (tip) of the substrate with the hydrophilic coating layer in the circumferential direction.

[0083] When it is difficult to immerse only a portion of the outer surface of the substrate in the coating liquid, the outer surface portion of the substrate that does not require the formation of a hydrophilic coating layer can be protected (coated, etc.) with a suitable detachable member or material. The substrate can then be immersed in the coating liquid to coat it with the coating liquid. After that, the protective member (material) covering the outer surface portion of the substrate that does not require the formation of a hydrophilic coating layer can be removed, and the substrate can then be reacted by heat treatment or the like to form a hydrophilic coating layer on the desired portion of the outer surface of the substrate. However, the present invention is not limited to these formation methods, and a conventionally known method can be appropriately used to form a hydrophilic coating layer. For example, when it is difficult to immerse only a portion of the outer surface of the substrate in the coating liquid, other coating methods (e.g., applying the coating liquid to a predetermined surface portion of a medical device using an application device such as a sprayer, bar coater, die coater, reverse coater, comma coater, gravure coater, spray coater, or doctor knife) can be used instead of the immersion method. In addition, when the structure of the catheter requires that both the outer and inner surfaces of the cylindrical device have a hydrophilic coating layer, the immersion method (dipping method) is preferably used because it allows both the outer and inner surfaces to be coated at the same time.

[0084] The coating liquid is preferably applied in an amount such that the thickness (dry film thickness) of the resulting coating (hydrophilic coating layer) falls within the range of the thickness of the hydrophilic coating layer shown in the above-mentioned "hydrophilic coating layer" column. Furthermore, when forming a hydrophilic coating layer on the outer surface within a certain range in the axial direction from the tip (tip) of the substrate, the coating liquid is preferably applied so that the range falls within the "certain distance" or "axial length of the hydrophilic coating layer" shown in the above-mentioned "hydrophilic coating layer" column.

[0085] (III) Heat Treatment Step A method for manufacturing a catheter according to one embodiment may include the step of applying a coating liquid to the outer surface of a catheter substrate to form a coating film (coating layer) in the above-mentioned (II) coating step, and then performing a heat treatment on the substrate by gradually increasing the heating temperature. In other words, a catheter according to one embodiment of the present invention may be produced by a manufacturing method including the step of applying a coating liquid to the outer surface of a substrate to form a coating film (coating layer) in the above-mentioned coating step, and then performing a heat treatment on the substrate by gradually increasing the heating temperature. By gradually increasing the heating temperature, the hydrophilic coating layer is endowed with both excellent durability and lubricity, and the catheter also has excellent durability and surface lubricity.

[0086] The range of the heating temperature in the heat treatment step according to one embodiment is not particularly limited, but is preferably 50° C. to 200° C., and more preferably 100° C. to 180° C. By maintaining (heat treating) the temperature within such a range, a strong hydrophilic coating layer is formed.

[0087] The heating time in the heat treatment step according to one embodiment is not particularly limited, but is preferably 15 minutes to 20 hours, more preferably 30 minutes to 12 hours. By setting the heating time in this range, the crosslinking reaction in the block copolymer is effectively promoted, and a stronger coating layer (hydrophilic coating layer) is formed, thereby maintaining high surface lubricity for a longer period of time.

[0088] Here, the heat treatment "increasing the temperature stepwise" preferably includes a step of maintaining the predetermined heating temperature for a certain period of time and a step of increasing the temperature to the predetermined heating temperature without stopping the temperature increase. Furthermore, in one embodiment, the heat treatment "increasing the temperature stepwise" preferably includes at least one cycle of maintaining the predetermined heating temperature for a certain period of time and increasing the temperature to the predetermined heating temperature without stopping the temperature increase. Therefore, a catheter manufacturing method according to one embodiment preferably includes a step of performing a heat treatment in which the heating temperature is increased stepwise so as to obtain a catheter having a hydrophilic coating layer on at least a portion of the outer surface of a substrate, wherein the number of particles having a size of 10 μm or more and less than 50 μm detected by a particle test is 2,000 or less, and the sliding resistance value measured in a pinch test over 20 sliding cycles is 5 gf or more and 20 gf or less.

[0089] (IV) Other Steps In one embodiment of the production method, a drying step may be included before the heat treatment step. In the drying step, excess solvent is removed, allowing the subsequent heat treatment step to proceed more efficiently. The temperature of the drying step is not particularly limited, but is preferably 10°C or higher and lower than 50°C, and more preferably 20 to 30°C. The drying time is also not particularly limited, but is preferably 15 minutes to 20 hours, more preferably 30 minutes to 12 hours. The pressure conditions during drying are also not particularly limited, and drying can be performed under normal pressure (atmospheric pressure), or under increased or reduced pressure.

[0090] As the means (apparatus) for carrying out the heat treatment step and drying step, for example, an oven, a reduced pressure dryer, etc. can be used, but in the case of natural drying, no particular drying means (apparatus) is required.

[0091] <Uses of the Catheter> The catheter 1 according to one embodiment can be used as a variety of catheters, such as a guiding catheter, angiography catheter, microcatheter, guidewire support catheter, balloon catheter, stent delivery catheter, atherectomy catheter, and diagnostic imaging catheter. However, it is preferably used as a guidewire support catheter that supports a guidewire. This is because the excellent lubricity and durability of the catheter according to the present invention make it particularly suitable for a guidewire support catheter used to pass through a stenosed lesion. Furthermore, in this case, the catheter 1 according to one embodiment is preferably used with a guidewire having an outer diameter of 0.012 inches to 0.016 inches, although this is not particularly limited. Guidewires having an outer diameter within this range are particularly used for stenosed lesions, and therefore the guidewire support catheter according to one embodiment of the present invention, which has excellent lubricity and durability, is particularly suitable for use in supporting such guidewires.

[0092] Although the embodiments of the present invention have been described in detail above, it is clear that these are for illustrative and exemplary purposes only and are not limiting, and the scope of the present invention should be interpreted by the appended claims.

[0093] The present invention will be described below with reference to examples, although the present invention is not limited to these examples.

[0094] [Fabrication and Preparation of Catheters of Examples and Comparative Examples] Catheters of Example 1 and Comparative Example 1 were fabricated according to the following procedure. Additionally, catheters of Comparative Examples 2 and 3 were commercially available.

[0095] Synthesis Example 1: Synthesis of Block Copolymer (1) Block copolymer (1) was produced by the following reaction.

[0096]

[0097] 29.7 g of triethylene glycol was added dropwise to 72.3 g of adipic acid dichloride at 50°C, and then the mixture was stirred at 50°C for 3 hours to remove hydrochloric acid under reduced pressure, yielding an oligoester. Next, 4.5 g of methyl ethyl ketone was added to 22.5 g of the obtained oligoester, and this was added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of dioctyl phosphate as a surfactant, and 120 g of water, and the mixture was allowed to react at -5°C for 20 minutes. The obtained product was repeatedly washed with water and methanol and then dried to yield a polyperoxide (PPO) having multiple peroxide groups in the molecule.

[0098] Next, 0.5 g of this PPO, 9.5 g of glycidyl methacrylate (GMA), and 30 g of benzene as a solvent were polymerized at 80°C for 2 hours with stirring under reduced pressure. The reaction product obtained after the polymerization was reprecipitated using diethyl ether to obtain polyglycidyl methacrylate (PPO-GMA) having multiple peroxide groups in the molecule.

[0099] Subsequently, 1.35 g of the obtained PPO-GMA (corresponding to 9.5 mmol of GMA) was added to 11.2 g (113 mmol) of N,N-dimethylacrylamide (DMAA) and 90 g of dimethyl sulfoxide as a solvent, and the mixture was reacted at 80°C for 18 hours. The reaction product obtained after the reaction was reprecipitated with hexane and recovered to obtain block copolymer (1) (structural unit (A):structural unit (B) = GMA:DMAA = 1:12 (molar ratio)). The weight average molecular weight (Mw) of block copolymer (1) measured by gel permeation chromatography (GPC, polystyrene equivalent) was approximately 1.5 million.

[0100] [Manufacturing of the Catheter of Example 1] In Example 1, the following tubular catheter material was used as the catheter material. - Inner diameter: tip 0.42 mm, shaft 0.48 mm - Outer diameter: tip 0.69 mm, shaft 0.75 mm - Length: 150 cm Here, the inner diameter of the tip portion is the diameter of a pin gauge that can be inserted into the tip of the catheter material, and the inner diameter of the shaft portion is the diameter of the core wire used to mold the catheter material. The outer diameter of the tip portion is the value measured at the very tip of the catheter material using a laser outer diameter measuring device, and the outer diameter of the shaft portion is the value measured at a point approximately 20 cm in the axial direction from the base end of the shaft portion of the catheter material using a laser outer diameter measuring device.

[0101] A coating solution was prepared by dissolving the block copolymer (1) obtained in Synthesis Example 1 in N,N-dimethylformamide (DMF) to a final concentration of 5.2% by mass. The distal 40 cm of the substrate of the catheter material was wiped with isopropyl alcohol (IPA), then immersed in the coating solution, pulled up at a pulling rate of 15 mm / min, and dried at room temperature (25°C) for 2 hours, thereby forming a coating film on the entire outer surface of the substrate from the distal end 40 cm. The catheter material on which the coating film had been formed was then placed in an oven, and the temperature inside the oven was increased to 100°C without stopping the temperature increase. After reaching 100°C, the temperature was gradually increased to 140°C while the material was stored for 3 hours for heat drying, thereby producing a catheter of Example 1 having a coating layer (hydrophilic coating layer) containing a crosslinked copolymer derived from the block copolymer. The coating layer covered the outer surface of the catheter from the distal end to 40 cm in the longitudinal direction, and the surface area of ​​the coating layer was 9.42 cm. ２ The thickness of the coating layer measured with a microscope film thickness measuring instrument (F40, manufactured by Filmetrics) was 1.4 μm.

[0102] [Production of the catheter of Comparative Example 1] A catheter having a coating layer (hydrophilic coating layer) was produced in the same manner as in Example 1, except that the catheter material on which the coating film had been formed was placed in an oven, the temperature in the oven was raised to 140°C without stopping the temperature increase, and the catheter was stored at 140°C for 3 hours.

[0103] [Preparation of catheter in Comparative Example 2] A commercially available catheter, CXI (registered trademark) support catheter (CXI-2.3-14-150-0, manufactured by COOK Medical), was used as is as the catheter in Comparative Example 2. In this catheter, the thickness of the film present on the substrate surface was 0.25 μm, the outer diameter of the tip was 0.53 mm, and the shaft was 0.72 mm. The film thickness was measured in the same manner as in Example 1.

[0104] [Preparation of catheter in Comparative Example 3] A commercially available catheter, TRAILBLAZER (registered trademark) support catheter (ASC-014-150, manufactured by Medtronic), was used as is as the catheter in Comparative Example 3. In this catheter, the thickness of the film present on the substrate surface was 0.86 μm, the outer diameter of the tip portion was 0.43 mm, and the outer diameter of the shaft portion was 0.76 mm. The film thickness was measured in the same manner as in Example 1.

[0105] [Evaluation of the number of fine particles] The catheters of Example 1 and Comparative Examples 1 to 3 were evaluated for the number of fine particles (evaluation of the durability of the hydrophilic coating layer) according to the following method. Two samples (referred to as Sample A and Sample B, respectively) were prepared for the catheters of Example 1 and Comparative Examples 1 to 3 and used for the evaluation. The results are shown in Table 1.

[0106] [Method for particle testing] (Pre-test preparation) 1. A φ5 mm hole was drilled in the inner lid of a 200 mL mayonnaise bottle. 2. The 200 mL mayonnaise bottle, inner lid, and lid were washed with detergent, rinsing to ensure that no detergent remained. 3. The mayonnaise bottle from step 2 above was lightly rinsed with distilled water, and then a small amount of distilled water was added, the lid was closed, and the bottle was shaken at least 10 times before discarding the distilled water. This process was repeated three times. 4. A 500 mL mayonnaise bottle was washed in the same manner as steps 2 and 3 above, and then distilled water was added and the bottle was warmed to 37°C in a thermostatic chamber. 5. As shown in Figures 2-1 and 2-2, a pin was attached to the particle testing jig, and a PTFE tube with an inner diameter of 3 mm and an outer diameter of 4 mm was set in it, forming a test device. 6. The above step 5 above was used in step 2 above. A NaviCross (registered trademark) (0.035 inch, 65 cm product with a straight tip) was inserted as a sample tube into the PTFE tube of Example 1. 7. Using a non-silicone syringe, a total of 100 mL or more of the distilled water described in Example 4 above was injected into the hub of the sample tube of Example 6 above, and the test system was washed inside the sample tube and the PTFE tube beyond the tip of the sample tube. 8. The tip of the PTFE tube was sealed with forceps, the fitting between the sample tube's kink-resistant protector and the PTFE tube was loosened, and the space between the PTFE tube and the sample tube was washed with 100 mL or more of the distilled water described in Example 4 above. 9. The sample tube's kink-resistant protector was fitted to the PTFE tube, the forceps were removed, and the test system (inside the sample tube, the space between the sample tube and the PTFE tube, and inside the PTFE tube beyond the tip of the sample tube) was filled with the distilled water described in Example 4 above. 10. An inner lid with a hole was placed on a 200 mL mayonnaise bottle, and a waterproof PTFE tube was passed through the hole to create a liquid collection bottle.

[0107] The test apparatus will now be described in detail. As shown in Figures 2-1 and 2-2, the test apparatus was a PTFE tube with an inner diameter of 3 mm and an outer diameter of 4 mm, arranged to have a straight path 2a and serpentine paths (first serpentine portion 2b, second serpentine portion 2c, and third serpentine portion 2d). The straight path 2a was 30 cm long, the first serpentine portion 2b had a radius of curvature of 15 mm and both ends were 80 mm long, the second serpentine portion 2c had a radius of curvature of 10 mm and both ends were 60 mm long, and the third serpentine portion 2d had a radius of curvature of 40 mm and both ends were 40 mm long.

[0108] (Collection of test liquid) 1. The forceps at the tip of the PTFE tube were removed, and 100 mL of distilled water warmed to 37°C was injected into the hub of the sample tube using a non-silicone syringe to collect a blank liquid. 2. The test system was sealed with forceps. 3. Two trays that had been washed with detergent and distilled water were filled with distilled water, and the sample was immersed and the inner surface was flushed with distilled water. 4. Similarly, a Glidewire (registered trademark) Advantage 0.014 inch (manufactured by Terumo Corporation, hereinafter also referred to as GW) was immersed in the tray and inserted into the sample, and the sample and GW were fixed with a clip hub. 5. 4. was transferred to another tray and immersed again. 6. The sample was inserted into the sample tube and slid back and forth 10 times over a distance of 100 cm at a speed of 20 mm / sec. 7. The specimen was removed, the forceps were removed, and 100 mL of distilled water was poured into the hub of the specimen tube to collect the test liquid.

[0109] (Particle Measurement) 1. The automatic particle counter (HIAC 9703+, manufactured by Beckman Coulter) was turned on and it was confirmed that at least one hour had passed. 2. Pre-test preparations were made according to the manual for the automatic particle counter. 3. The following measurement conditions were set.

[0110] Stirrer rotation speed: 200 rpm Number of measurements: 4 times (initial data discarded) Measurement volume: 10 mL Measurement target (particle size): 10 μm, 25 μm, and 50 μm Here, if the measurement target is 10 μm, the number of particles 10 μm or larger shall be measured. Also, if the measurement target is 25 μm, the number of particles 25 μm or larger shall be measured. Also, if the measurement target is 50 μm, the number of particles 50 μm or larger shall be measured. 4. A stirring bar that had been scrubbed with distilled water was placed in a collection bottle containing the test liquid or blank liquid, and the bottle was set on the test stand. After stirring for 30 seconds or more, measurements were performed. 5. The number of particles was calculated according to the following formula.

[0111] Number of particles (number / 100 mL) = ((number of particles in sample (number / 1 mL)) - (number of particles in blank (number / 1 mL))) × 100

[0112]

[0113] From the above results, the number of particles of 10 μm or more and less than 50 μm detected by the particle test for the catheter of Example 1 was 2000 or less. On the other hand, the number of particles of 10 μm or more and less than 50 μm detected by the particle test for the catheters of Comparative Examples 1 to 3 was more than 2000. From these results, it was found that the catheter of Example 1 has excellent durability.

[0114] [Evaluation of Sliding Resistance] The catheters of Example 1 and Comparative Examples 1 to 3 were subjected to a pinch test according to the following method to evaluate sliding resistance (surface lubricity of the hydrophilic coating layer). The evaluation was performed on two samples: one cut from the tip of each catheter after the microparticle test at a length of 15 cm in the axial direction (referred to as Sample 1, also simply referred to as S1), and the other cut at a length of 15 cm in the axial direction from the cut portion (referred to as Sample 2, also simply referred to as S2). The results are shown in Table 2 and Figures 3 and 4. 1. The sliding tester (Oak Riversha DL1000) was turned on, and a container filled with tap water was placed inside. 2. It was confirmed that the manufacturer's standard silicone rubber (trade name: 'Gripper Pad Cassettes 0.5' Silicone Rubber, Shore hardness: 60) was attached to the gripper. 3. The height of the gripper was adjusted, and the entire gripper was submerged and fixed in the container in 1. 4. A 0.42 mm diameter core was inserted, and the catheter and core were fixed with a pin vise attached to the testing machine. 5. The samples were set on the load cell so that the distance from the tip of each sample to the bottom end of the gripper was 5 cm or more. 6. Measurements were carried out under the following conditions: Measurement distance: 5 cm Number of cycles: 20 Sliding speed: 20 mm / s Grip force: 500 gf 7. The values ​​measured in each of the 1st to 20th sliding runs were averaged between measurement distances of 15 mm and 48 mm, and this was used as the sliding resistance value for each run.

[0115]

[0116] As shown in Table 2 and Figure 3, the catheter of Example 1 had a sliding resistance value of 5 gf or more and 20 gf or less in each of 20 sliding cycles measured in the pinch test. These results demonstrate that the catheter of Example 1 has excellent surface lubricity and maintains this excellent surface lubricity, i.e., has excellent durability.

[0117] Furthermore, for the catheter of Example 1, the sliding resistance value for each of the 20 sliding cycles measured in the pinch test was equal to or less than the sliding resistance value for the first sliding cycle. These results demonstrate that the catheter of Example 1 maintains excellent surface lubricity even after multiple sliding cycles. Additionally, for the catheter of Example 1, when the sliding resistance value for the 20th sliding cycle measured in the pinch test is designated as X and the smallest sliding resistance value among the sliding resistance values ​​for the first to 19th cycles is designated as Y, the value of {(Y-X) / X} x 100(%) was -10% to 10% (S1 was -1%, S2 was 0.2%). These results also demonstrate that the catheter of Example 1 not only exhibits excellent surface lubricity, but also maintains excellent surface lubricity, i.e., has excellent durability.

[0118] On the other hand, the catheters of Comparative Example 1 and Comparative Example 3 had sliding resistance values ​​exceeding 20 gf each time measured over a total of 20 sliding cycles in the pinch test. Furthermore, the catheter of Comparative Example 3 had a sliding resistance value of 20 times greater than the sliding resistance value of the first time in the pinch test. Furthermore, the catheters of Comparative Example 2 (S1) and Comparative Example 3 had values ​​of {(Y-X) / X} x 100(%) outside the range of -10% to 10%. These results indicate that the catheters of Comparative Example 1, Comparative Example 2 (S1), and Comparative Example 3 had inferior sliding properties, i.e., surface lubricity, and also inferior durability, compared to the catheter of Example 1. Furthermore, although S2 of Comparative Example 2 showed excellent sliding properties equivalent to those of Example 1, the results of the microparticle test were inferior.

[0119] This application is based on Japanese Patent Application No. 2024-055699, filed on March 29, 2024, the disclosure of which is incorporated herein by reference in its entirety.

[0120] 1 catheter, 10 shaft portion, 10H lumen, 20 tip portion, 30 hub, 40 anti-kink protector, 50 hydrophilic coating layer, 60 substrate, 2a straight path, 2b first meandering portion, 2c second meandering portion, 2d third meandering portion.

Claims

1. A catheter having a hydrophilic coating layer on at least a portion of the outer surface of a substrate, wherein the number of particles of 10 μm or more and less than 50 μm detected by a particle test is 2,000 or less, and the sliding resistance value measured in a pinch test over 20 sliding cycles is 5 gf or more and 20 gf or less.

2. The catheter according to claim 1, wherein the outer diameter of the tip portion of the base material is 0.3 mm to 0.9 mm, and the outer diameter of the shaft portion is 0.4 mm to 1 mm.

3. A catheter according to claim 1 or 2, wherein the inner diameter of the tip portion of the base material is 0.1 mm to 0.6 mm, and the inner diameter of the shaft portion is 0.2 mm to 0.7 mm.

4. A catheter according to claim 1 or 2, wherein the sliding resistance value measured for each of a total of 20 sliding operations in the pinch test is equal to or less than the sliding resistance value measured for the first sliding operation.

5. The catheter according to claim 1 or 2, wherein the value of {(Y-X) / X} x 100(%) is -10% to 10%, where X is the sliding resistance value at the 20th time measured in the pinch test and Y is the smallest sliding resistance value among the sliding resistance values ​​at the 1st to 19th times.

6. The catheter according to claim 1 or 2, which is a guidewire support catheter.

7. The catheter of claim 6, which is used with a guidewire having an outer diameter of 0.012 inches to 0.016 inches.

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