Dilator and sheath assembly

Abstract

Provided is a dilator excellent in operability in a procedure using a sheath assembly. A dilator according to the present invention comprises a base material layer and a surface lubricating layer supported on at least a part of the base material layer. The base material layer contains a polyolefin resin and a contrast agent. The surface lubricating layer contains a block copolymer having a constituent unit (A) derived from a reactive monomer having an epoxy group and a constituent unit (B) derived from a hydrophilic monomer.

Description

Dilator and sheath assembly

[0001] The present invention relates to a dilator and a sheath assembly including the dilator.

[0002] Conventionally, a sheath assembly is known as a medical instrument used for inserting a medical device or the like into a living body lumen.

[0003] The sheath assembly includes a medical elongated body (sheath) having a hollow tubular catheter body (sheath tube) with a lumen formed therein and a hub portion disposed at the proximal end of the catheter body, and a dilator that can be inserted into the lumen (lumen) of the catheter body.

[0004] In a procedure using a sheath assembly, an operator or the like inserts a dilator into the catheter body, protrudes the tip of the dilator from the tip of the catheter body, and inserts the sheath tube into a blood vessel (living body lumen) through a perforation formed in the skin or the like. When the tip of the sheath assembly reaches the target position, the operator or the like removes the dilator from the catheter body while the catheter body is inserted into the blood vessel. Then, the operator or the like can insert various medical devices such as a balloon catheter into the blood vessel by using the lumen of the catheter body as an access path connecting the inside of the blood vessel and the outside of the living body.

[0005] In recent years, various reports have been made to improve the operability of the sheath assembly in the above-described procedure. For example, Japanese Patent Application Laid-Open No. 2016-192982 describes a sheath assembly that can be easily inserted into a perforation formed in the skin or the like by including a dilator having a first tube portion with a smooth outer surface and a second tube portion inclined with respect to the axial direction.

[0006] Further, for example, Japanese Patent Application Laid-Open No. 2012-513294 describes a moving expander (dilator) provided with lubricity by applying a silicone coating or the like to the outer layer of a fluoropolymer such as PTFE, FEP, or PFA.

[0007] A silicone-coated dilator, such as the one disclosed in Japanese Patent Publication No. 2012-513294, exhibits good maneuverability within blood vessels. However, there is a need for technology that can further improve maneuverability when using dilators (sheath assemblies equipped with dilators) for purposes such as reducing tissue damage to blood vessels. In particular, since blood vessels requiring the above-mentioned procedures often have hardened stenoses or sharply bent sections, conventional sheath assemblies equipped with dilators may have high frictional resistance when pushed to the desired position, making it difficult to pass through stenoses and bends.

[0008] The present invention has been made in view of the above circumstances, and aims to provide a dilator and a sheath assembly equipped with the dilator that are excellent in operability (particularly when passing through narrowed or curved parts of blood vessels) in procedures using a sheath assembly.

[0009] The inventors of the present invention conducted diligent research to solve the above problems. As a result, they discovered that the above objectives can be achieved by a dilator having a predetermined base material layer and a surface lubrication layer containing a predetermined hydrophilic block copolymer, and thus completed the present invention.

[0010] The above objective can be achieved by the present invention having the following configuration, and the present invention encompasses the following aspects and forms.

[0011] One aspect of the present invention is: 1. A dilator comprising a base layer and a surface lubricating layer supported on at least a portion of the base layer, wherein the base layer comprises a polyolefin resin and a contrast agent, and the surface lubricating layer comprises a block copolymer having constituent units (A) derived from a reactive monomer having an epoxy group and constituent units (B) derived from a hydrophilic monomer; 2. In the dilator described in 1. above, it is preferable that the surface lubricating layer further comprises at least one selected from the group consisting of polyvinyl chloride and silicone compounds; 3. In the dilator described in 1. or 2. above, it is preferable that the surface lubricating layer is supported on the base layer at least at the tip of the dilator; 4. In the dilator described in any of 1. to 3. above, it is preferable that the contrast agent comprises at least one selected from the group consisting of bismuth compounds and barium compounds; 5. In the dilator described in any of 1. to 4. above, it is preferable that the polyolefin resin is a polypropylene resin; 6. In the dilator described in 1. to 5. above In the dilator described in any of the above, it is preferable that the inner diameter of the tip is 2.0 mm or less; 7. In the dilator described in any of the above 1. to 6., it is preferable that the sliding resistance value of the surface lubrication layer is 1 gf or more and 30 gf or less.

[0012] Another aspect of the present invention is 8. a sheath assembly comprising a dilator as described in any of 1 to 7 above.

[0013] This is a schematic partial cross-sectional view showing the surface lamination structure of a typical embodiment of the dilator according to the present invention. This is a schematic diagram showing the dilator and sheath according to the present invention. This is a schematic diagram showing a test apparatus for evaluating the sliding properties and durability of the dilator according to this embodiment, showing a pair of contact members sandwiching the dilator. This is a schematic diagram showing a test apparatus for evaluating the sliding properties and durability of the dilator according to this embodiment, showing the dilator separated from a pair of contact members. This is a schematic diagram showing an operability evaluation apparatus for evaluating the operability of the dilator, etc., according to the present invention. This is a schematic diagram showing the fixing plate of the operability evaluation apparatus for evaluating the operability of the dilator, etc., according to the present invention. This is a diagram for explaining the operation of the evaluation using the operability evaluation apparatus.

[0014] A dilator according to one aspect of the present invention comprises a base layer and a surface lubricating layer supported on at least a portion of the base layer, wherein the base layer comprises a polyolefin resin and a contrast agent, and the surface lubricating layer comprises a block copolymer having constituent units (A) derived from a reactive monomer having an epoxy group and constituent units (B) derived from a hydrophilic monomer. A dilator having the above configuration will hereinafter also be referred to as "the dilator according to the present invention" or "dilator".

[0015] Furthermore, a sheath assembly according to another aspect of the present invention includes the dilator described above. A sheath assembly having this configuration will hereinafter also be referred to as "the sheath assembly according to the present invention" or "sheath assembly". The dilator according to one aspect of the present invention and the sheath assembly equipped with the dilator offer excellent operability (particularly when passing through narrowed or bent portions of blood vessels).

[0016] In this specification, a constituent unit (A) derived from a reactive monomer having an epoxy group is also referred to simply as "constituent unit (A) according to the present invention" or "constituent unit (A)". In this specification, a constituent unit (B) derived from a hydrophilic monomer is also referred to simply as "constituent unit (B) according to the present invention" or "constituent unit (B)". In this specification, a block copolymer having constituent units (A) and (B) is also referred to simply as "block copolymer according to the present invention", "hydrophilic block copolymer", or "block copolymer".

[0017] In this specification, when a constituent unit is defined as "derived from" a monomer, it means that the constituent unit is produced by the cleavage of one of the polymerizable unsaturated double bonds of the corresponding monomer.

[0018] In this specification, the term "(meth)acrylic" encompasses both acrylic and methacrylic. Therefore, for example, the term "(meth)acrylic acid" encompasses both acrylic acid and methacrylic acid. Similarly, the term "(meth)acryloyl" encompasses both acryloyl and methacryloyl. Therefore, for example, the term "(meth)acryloyl group" encompasses both acryloyl and methacryloyl groups. Furthermore, similarly, the term "(meth)acrylate" encompasses both acrylate and methacrylate. For example, the term "alkoxyalkyl (meth)acrylate" encompasses both alkoxyalkyl acrylate and alkoxyalkyl methacrylate.

[0019] Furthermore, throughout this specification, singular expressions should be understood to include the concept of their plural form unless otherwise specified. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the concept of their plural form unless otherwise specified. Also, terms used in this specification should be understood to have the meaning commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by those skilled in the art to which this invention belongs. In case of any conflict, this specification (including definitions) shall prevail. This invention is not limited to the embodiments described below and can be modified in various ways within the scope of the claims. Also, in this specification, "X to Y" indicates a range including X and Y, meaning "X or greater and Y or less." Also, "X and / or Y" means at least one of X and Y, including X alone, Y alone, and combinations of X and Y. Also, "%" of concentration refers to mass concentration "mass%" unless otherwise specified.

[0020] Unless otherwise specified, measurements of operation and physical properties are performed under room temperature (20-25°C) / relative humidity of 40-50% RH.

[0021] [Dilator] The dilator according to the present invention comprises a base layer and a surface lubricating layer supported on at least a portion of the base layer. The base layer is characterized in that it contains a polyolefin resin and a contrast agent, and the surface lubricating layer contains a block copolymer having constituent units (A) derived from a reactive monomer having an epoxy group and constituent units (B) derived from a hydrophilic monomer. The base layer has a tubular shape with a lumen (guide wire lumen) that is continuous from the tip to the base.

[0022] A preferred embodiment of the dilator according to the present invention will be described below with reference to the attached drawings.

[0023] Figure 1 is a schematic partial cross-sectional view showing the laminated surface structure of a typical embodiment of the dilator according to the present invention. In Figure 1, each reference numeral represents the following: 1 represents the base layer; 2 represents the surface lubrication layer; 3 represents the lumen (guide wire lumen) that extends from the tip to the base; and 10 represents the dilator according to the present invention.

[0024] As shown in Figure 1, the dilator 10 of this embodiment comprises a base layer 1 and a surface lubricating layer 2 containing a block copolymer, which is provided on at least a portion of the base layer 1 (in the figure, an example is shown where it is provided so as to cover the outer surface of the base layer 1 in the circumferential direction).

[0025] The dilator will be described in detail below, component by component.

[0026] <Substrate layer (substrate)> The substrate layer used in this embodiment includes a polyolefin resin and a contrast agent.

[0027] (Polyolefin resin) Examples of polyolefin resins included in the base layer of the dilator according to one embodiment include polyethylene resin and polypropylene resin, but polypropylene resin is preferred from the viewpoint of heat resistance and chemical resistance (solvent resistance).

[0028] In one embodiment of the dilator, the polyolefin resin content (mass%) in the base layer is preferably 35% by mass or more, and more preferably 50% by mass or more, relative to the total mass of the base layer. Furthermore, the polyolefin resin content (mass%) in the base layer is preferably 90% by mass or less, and more preferably 80% by mass or less, relative to the total mass of the base layer. For example, the polyolefin resin content (mass%) in the base layer of the dilator is preferably 35% by mass to 90% by mass, more preferably 50% by mass to 80% by mass, and for example, 70% by mass. By having the polyolefin resin content in the base layer within the above range, it becomes easier to obtain sufficient strength and appropriate hardness as a dilator.

[0029] (Contrast agent) The contrast agent (X-ray contrast agent) contained in the base layer of the dilator according to one embodiment is not particularly limited as long as it is a substance that does not transmit X-rays, but examples include bismuth compounds, barium compounds, and tungsten. In particular, the base layer preferably contains at least one selected from the group consisting of bismuth compounds and barium compounds, from the viewpoint of contrast performance and from the viewpoint of the surface lubricating layer (block copolymer) described later being easily supported on the surface of the base layer. Furthermore, the bismuth compound is not particularly limited, but bismuth subcarbonate and / or bismuth oxide is preferably used, and the barium compound is not particularly limited, but barium sulfate is preferably used. That is, from the viewpoint of more easily obtaining the effect of the contrast agent described above, the base layer of the dilator according to one embodiment is more preferably to contain at least one selected from the group consisting of bismuth subcarbonate, bismuth oxide, and barium sulfate, and even more preferably to contain bismuth subcarbonate and / or bismuth oxide.

[0030] The inclusion of a contrast agent in the dilator allows its position inside the body to be confirmed under X-ray fluoroscopy. Furthermore, the inventors have discovered that while conventional dilators could not adequately support the surface lubrication layer on the substrate layer, the dilator according to the present invention, by including a contrast agent in the substrate layer, can adequately support the surface lubrication layer on the substrate layer. This is thought to be because the contrast agent in the substrate layer acts as a catalyst, causing the contrast agent to cleave the epoxy groups of the block copolymer contained in the surface lubrication layer at the interface between the surface lubrication layer and the substrate layer, thereby promoting crosslinking between the block copolymer and the substrate layer. The preferred contrast agents mentioned above (bismuth compounds and barium compounds) are thought to exhibit such catalytic activity more readily and have superior effect in promoting crosslinking between the block copolymer and the substrate layer. However, this mechanism is speculative and not limited thereto.

[0031] The contrast agent contained in the substrate layer of the dilator according to one embodiment is preferably in particulate form. Furthermore, the average particle size of the contrast agent is preferably 30 μm or more and 60 μm or less, and more preferably 45 μm or more and 50 μm or less. When the average particle size of the contrast agent contained in the substrate layer is within the above range, more epoxy groups of the block copolymer are cleaved by the contrast agent, and crosslinking between the block copolymer and the substrate layer is further promoted, so that the surface lubrication layer is more easily supported on the substrate layer with sufficient strength. Note that the average particle size is the volume average particle size measured by dynamic light scattering, but is not limited to this. For example, the average particle size of the contrast agent may be measured using a Coulter counter.

[0032] The contrast agent content (mass%) in the base layer of the dilator according to one embodiment is preferably 10% by mass or more and 40% by mass or less, more preferably 15% by mass or more and 35% by mass or less, and as an example, 30% by mass. By having the contrast agent content in the base layer within the above range, the surface lubrication layer described later is more easily supported on the base layer with sufficient strength.

[0033] The ratio of the polyolefin resin content (mass%) to the contrast agent content (mass%) in the base layer of the dilator according to one embodiment (polyolefin resin content (mass%) / contrast agent content (mass%) is preferably 0.8 to 9, more preferably 1 to 6, even more preferably 1 to 3, and particularly preferably 2 to 2.5. By having the ratio of the polyolefin resin content (mass%) to the contrast agent content (mass%) in the base layer within the above range, the surface lubricating layer, described later, is more easily supported on the base layer with sufficient strength.

[0034] (Other components) The base layer may contain other components in addition to polyolefin resin and contrast agent. The other components are not particularly limited and are appropriately selected depending on the application of the dilator, but one example is polymer materials other than polyolefin resin. Examples of such polymer materials include polyamide resins such as nylon 6, nylon 11, nylon 12, and nylon 66 (all registered trademarks); polyester resins such as polyethylene terephthalate (PET), polytrimethylene terephthalate (PTT), polybutylene terephthalate (PBT), and polyethylene naphthalate (PEN); styrene resins such as polystyrene; epoxy resins; urethane resins; diallyl phthalate resins (allyl resins); polycarbonate resins; fluororesins such as polytetrafluoroethylene (PTFE) and ePTFE (expanded polytetrafluoroethylene); polyurethane resins; amino resins (urea resins, melamine resins, benzoguanamine resins); acrylic resins; polyacetal resins; vinyl acetate resins; phenolic resins; vinyl chloride resins; silicone resins (silicon resins); polyether resins such as polyetheretherketone (PEEK); and polyimide resins. These may be used individually or in combination of two or more.

[0035] <Surface Lubrication Layer (Coating Layer)> The surface lubrication layer 2 is supported on at least a portion of the base material layer 1. The reason why the surface lubrication layer 2 is supported on at least a portion of the surface of the base material layer 1 is that it is not necessarily required that all surfaces (the entire surface) of the dilator be lubricated when wet. It is sufficient for the surface lubrication layer 2 to be supported only on the surface portion (which may be a portion or the entire surface) where the surface is required to be lubricated when wet.

[0036] As described later, from the viewpoint of further improving the operability of the dilator and sheath assembly, it is preferable that the surface lubrication layer be formed at least on the surface portion of the tip of the dilator.

[0037] (Block Copolymer) In the present invention, the block copolymer forms a surface lubricating layer supported on at least a portion of the substrate layer. That is, in the dilator according to the present invention, the surface lubricating layer includes the block copolymer. "Supported" means a state in which the surface lubricating layer is fixed in a state in which it does not easily detach from the surface of the substrate layer, and includes not only a form in which the entire surface of the substrate layer is completely covered by the surface lubricating layer, but also a form in which only a portion of the surface of the substrate layer is covered by the surface lubricating layer, that is, a form in which the surface lubricating layer is attached only to a portion of the surface of the substrate layer.

[0038] The block copolymer according to the present invention has a constituent unit (A) derived from a reactive monomer having an epoxy group and a constituent unit (B) derived from a hydrophilic monomer.

[0039] The reactive monomers having epoxy groups that constitute the block copolymer possess epoxy groups as reactive groups. By introducing such reactive monomer-derived constituent units (A) into the block copolymer, the epoxy groups open their rings, promoting crosslinking (bonding) between the block copolymers and increasing the film strength of the surface lubrication layer. Furthermore, crosslinking (bonding) between the block copolymer and the substrate layer can also occur through crosslinking between the polyolefin resin contained in the substrate layer and the ring-opened epoxy groups.

[0040] The reactive monomers constituting the block copolymer are not particularly limited as long as they have an epoxy group, and known compounds can be used. In particular, because it is easier to control the crosslinking or polymerization of the block copolymer, the reactive monomer having an epoxy group preferably contains 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.

[0041] Among them, considering that the crosslinking reaction can be further promoted, ease of production, etc., glycidyl (meth)acrylate is more preferable, and glycidyl methacrylate is particularly preferable. That is, in a more preferable form of the present invention, the reactive monomer having an epoxy group is at least one of glycidyl acrylate and glycidyl methacrylate. Further, in a particularly preferable form of the present invention, the reactive monomer having an epoxy group is glycidyl methacrylate.

[0042] The above reactive monomer 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 kind of reactive monomer, or a copolymer type composed of two or more of the above reactive monomers. In addition, the form of the structural unit (A) when two or more kinds are used may be a block copolymer or a random copolymer.

[0043] The hydrophilic monomer constituting the block copolymer has swelling properties when in contact with body fluids or aqueous solvents, and thus imparts lubricity (surface lubricity) to the dilator. Therefore, by introducing the structural unit (B) derived from such a hydrophilic monomer into the block copolymer, the lubricity (surface lubricity) of the dilator is improved, and the friction when the dilator contacts the lumen wall such as the blood vessel wall can be reduced. As a result, the operability in a procedure using the sheath assembly (particularly, the operability when passing through a stenotic portion or a bent portion of a blood vessel, etc.) can be improved.

[0044] The hydrophilic monomers constituting the block copolymer are not particularly limited as long as they possess the above-mentioned properties, and known compounds can be used. Examples include acrylamide and its derivatives, vinylpyrrolidone, acrylic acid and methacrylic acid and their derivatives, polyethylene glycol acrylate and its derivatives, monomers having sugars or phospholipids in their 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 Examples include acrylates, diethylene glycol mono(meth)acrylate, 1,6-hexanediol mono(meth)acrylate, pentaerythritol tri(meth)acrylate, dipentaerythritol penta(meth)acrylate, neopentyl glycol mono(meth)acrylate, trimethylolpropanedi(meth)acrylate, trimethylolethanedi(meth)acrylate, 2-hydroxy-3-phenyloxypropyl(meth)acrylate, 4-hydroxycyclohexyl(meth)acrylate, 2-hydroxy-3-phenyloxy(meth)acrylate, cyclohexanedimethanol mono(meth)acrylate, poly(ethylene glycol) methyl ether acrylate, and poly(ethylene glycol) methyl ether methacrylate. From the viewpoint of providing excellent lubricity, ease of synthesis, and operability, it is preferable that the hydrophilic monomer includes at least one selected from the group consisting of N,N-dimethylacrylamide, acrylamide, 2-hydroxyethyl methacrylate, and N-vinylpyrrolidone.

[0045] Among them, considering the imparting of excellent lubricity, ease of synthesis, and operability, N,N-dimethylacrylamide, acrylamide, or 2-hydroxyethyl methacrylate is more preferable, and N,N-dimethylacrylamide is particularly preferable. That is, in a more preferable 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. Further, in a particularly preferable embodiment of the present invention, the hydrophilic monomer is N,N-dimethylacrylamide.

[0046] The above hydrophilic monomer 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 a single hydrophilic monomer, or a copolymer type composed of two or more of the above hydrophilic monomers. In addition, the form of the structural unit (B) when using two or more may be a block copolymer or a random copolymer.

[0047] The block copolymer has a constituent unit (A) derived from the reactive monomer and a constituent unit (B) derived from the hydrophilic monomer. Here, the ratio of constituent unit (A) to constituent unit (B) is not particularly limited as long as the above effects are achieved. Considering good lubricity, lubricity retention, strength of the coating layer, and bonding with the substrate layer, the ratio of constituent unit (A) to constituent unit (B) (molar ratio of constituent unit (A):constituent unit (B)) is preferably 1:2 to 1:100, more preferably 1:2 to 1:50, even more preferably 1:5 to 1:50, and particularly preferably 1:10 to 1:30. Within this range, the surface lubrication layer can exhibit sufficient lubricity due to constituent unit (B), and sufficient coating layer strength, bonding with the substrate layer, and durability due to constituent unit (A). The molar ratio of constituent unit (A):constituent unit (B) can be controlled by adjusting the charging ratio (molar ratio) of each monomer during the manufacturing stage of the block copolymer. Therefore, the molar ratio of the reactive monomer having epoxy groups to the hydrophilic monomer in the production stage of the block copolymer is preferably 1:2 to 1:100, more preferably 1:2 to 1:50, even more preferably 1:5 to 1:50, and particularly preferably 1:10 to 1:30. The molar ratio of the above constituent unit (A):constituent unit (B) is determined, for example, by NMR measurement of the copolymer. １ H-NMR measurement, １３ This can be confirmed by performing C-NMR measurements, etc.

[0048] The block copolymer according to the present invention essentially contains structural unit (A) and structural unit (B), but may also have other structural units in addition to these structural units. When the block copolymer has other structural units, examples of other structural units 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 a homopolymer type composed of a single structural unit, or a copolymer type composed of two or more structural units. When two or more monomers constituting the above-mentioned other structural units are used, the segments composed of these monomers may be in the form of a block copolymer, a random copolymer, or an alternating copolymer.

[0049] When the block copolymer according to the present invention has other constituent units, the content of the other constituent units is preferably greater than 0 mol% and less than or equal to 5 mol% of the total constituent units constituting the block copolymer. That is, in the block copolymer according to the present invention, when the total of all constituent units constituting the block copolymer is taken as 100 mol%, the total content of constituent unit (A) and constituent unit (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 constituent unit (A) and constituent unit (B) (content of other constituent units = greater 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 durability due to constituent unit (A) and lubricity (surface lubricity) due to constituent unit (B). Preferably, the block copolymer according to the present invention does not contain the above-mentioned other constituent units (content of other constituent units = 0 mol%).

[0050] The composition of each constituent unit (constituent units (A) and (B), and other constituent units) can be measured by known methods. For example, the composition of a block copolymer solution １ By measuring the integral ratio of the intensities of each signal in the H-NMR spectrum, the composition (molar ratio) of the constituent units can be determined.

[0051] In one embodiment of the present invention, the block copolymer according to the present invention is substantially composed of a constituent 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 constituent 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 solely of the above constituent unit (A) and the above constituent unit (B).

[0052] In one embodiment of the present invention, the block copolymer according to the present invention is substantially composed of a constituent unit (A) derived from at least one reactive monomer of glycidyl acrylate and glycidyl methacrylate, and a constituent 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 solely of the above constituent unit (A) and the above constituent unit (B).

[0053] In one embodiment of the present invention, the block copolymer according to the present invention is substantially composed of a constituent unit (A) derived from glycidyl methacrylate (a reactive monomer having an epoxy group) and a constituent unit (B) derived from N,N-dimethylacrylamide (a hydrophilic monomer), or is composed solely of the above constituent unit (A) and the above constituent unit (B).

[0054] The weight-average molecular weight of the block copolymer is preferably 10,000 to 10,000,000 from the viewpoint of solubility. More preferably, the weight-average molecular weight of the block copolymer is 100,000 to 5,000,000 from the viewpoint of ease of preparation of the coating solution. In this specification, "weight-average molecular weight" refers to the value measured by gel permeation chromatography (GPC) using polystyrene as the standard substance.

[0055] The method for producing block copolymers is not particularly limited, and they can be produced by applying conventionally known polymerization methods, such as living radical polymerization, polymerization using macroinitiators, and polycondensation methods. Of these, living radical polymerization or polymerization using macroinitiators is preferred because it allows for easy control of the molecular weight and molecular weight distribution of constituent units (parts) derived from reactive monomers and constituent units (parts) derived from hydrophilic monomers. The living radical polymerization method is not particularly limited, but methods described in, for example, Japanese Patent Publication No. 11-263819, Japanese Patent Publication No. 2002-145971, Japanese Patent Publication No. 2006-316169, and atomic transfer radical polymerization (ATRP) can be applied in a similar manner or with appropriate modifications. Furthermore, in polymerization using macroinitiators, for example, a macroinitiator having a reactive site with a reactive functional group and a radically polymerizable group such as a peroxide group can be prepared, and then a block copolymer having hydrophilic sites and reactive sites can be produced by polymerizing the macroinitiator with monomers to form hydrophilic sites.

[0056] Furthermore, the polymerized block copolymer is preferably purified by general purification methods such as reprecipitation, dialysis, ultrafiltration, or extraction.

[0057] (Polyvinyl chloride and silicone compounds) The surface lubrication layer according to one embodiment of the present invention may further include, in addition to the block copolymer, at least one selected from the group consisting of polyvinyl chloride and silicone compounds. This can further improve the lubricity of the surface lubrication layer.

[0058] The surface lubrication layer according to one embodiment of the present invention preferably further contains polyvinyl chloride in addition to the block copolymer. When the surface lubrication layer contains polyvinyl chloride, the hydrogen chloride (HCl) produced by dechlorination cleaves the epoxy groups contained in the block copolymer, promoting crosslinking (bonding) between the block copolymers. This forms a surface lubrication layer with high film strength (a strong coating layer), which can be maintained well even after sliding against a more flexible and narrow biological lumen such as a blood vessel, and it is presumed that high lubricity (surface lubricity) can be maintained for a longer period of time (i.e., excellent surface lubricity can be maintained and sliding durability can be improved). As a result, it is thought that a dilator with improved operability can be obtained. Note that the above mechanism is a hypothesis and does not limit the technical scope of the present invention.

[0059] The weight-average molecular weight (Mw) of polyvinyl chloride is preferably 1,000 or more, more preferably 5,000 or more, and even more preferably 10,000 or more, from the viewpoint of promoting crosslinking and stability. Furthermore, from the viewpoint of solubility, the weight-average molecular weight of polyvinyl chloride is preferably 500,000 or less, more preferably 250,000 or less, and even more preferably 100,000 or less. As an example, the weight-average molecular weight (Mw) of polyvinyl chloride may be 1,000 to 500,000, 5,000 to 250,000, or 10,000 to 100,000.

[0060] The mass ratio of polyvinyl chloride to block copolymer (polyvinyl chloride:block copolymer) in the surface lubrication layer is not particularly limited. However, the mass ratio of polyvinyl chloride to block copolymer in the surface lubrication layer is preferably 0.001 to 1:1, more preferably 0.005 to 0.5:1, and even more preferably 0.01 to 0.1:1. When the mass ratio of polyvinyl chloride to block copolymer is within the above range, the lubricity (sliding properties) of the surface lubrication layer is sufficiently ensured, while the crosslinking of the block copolymer is sufficiently advanced without excessive advancement (crosslinking can be moderately promoted). Therefore, the lubricity and durability of the resulting surface lubrication layer can be fully exhibited. However, even if it falls outside the above range, it is still perfectly usable as long as it does not affect the effects of the present invention.

[0061] The surface lubrication layer according to one embodiment of the present invention preferably further contains a silicone compound in addition to the block copolymer. The silicone compound is not particularly limited, but may be a reactive silicone, a non-reactive silicone, or a combination thereof. In particular, the silicone compound preferably contains a reactive silicone from the viewpoint of forming a uniform film without phase separation with the block copolymer constituting the surface lubrication layer and obtaining stable sliding properties (surface lubricity). By including a reactive silicone together with the block copolymer, they can crosslink to form a network. The network of block copolymer and reactive silicone formed by the above crosslinking reaction becomes more likely to swell when wet, and excellent surface lubricity can be obtained, and such excellent surface lubricity can be obtained over a long period of time. As a result, it is presumed that a dilator with improved operability can be obtained. Note that the above mechanism is a presumption and does not limit the technical scope of the present invention.

[0062] Here, "reactive silicone" refers to a silicone compound having a reactive group that can react with a reactive group contained in a block copolymer, such as an epoxy group (or a glycidyl group).

[0063] Therefore, in this specification, "the surface lubricating layer contains a reactive silicone (as a silicone compound)" includes not only a form containing unreacted reactive silicone, but also a form that further contains a reaction product of the reactive silicone and the block copolymer in addition to the reactive silicone. Furthermore, "the surface lubricating layer contains a reactive silicone and a block copolymer (as a silicone compound)" includes not only a form containing unreacted reactive silicone and an unreacted block copolymer, but also a form that also contains a reaction product of the reactive silicone and the block copolymer. Here, the reaction rate between the reactive silicone and the block copolymer does not have to be 100%. That is, the surface lubricating layer may further contain at least one of the above-mentioned reaction product (reaction product) and unreacted reactive silicone.

[0064] The reactive groups that a reactive silicone possesses are not particularly limited, but examples include hydroxyl groups (-OH), carboxyl groups, and amino groups (-NH). ２ Examples include epoxy groups, ethylenically unsaturated groups, and alkoxysilyl groups. Therefore, in one embodiment, the reactive silicone preferably has at least one selected from the group consisting of hydroxyl groups (-OH), carboxyl groups, amino groups, epoxy groups, ethylenically unsaturated groups, and alkoxysilyl groups. More preferably, the reactive silicone has at least one selected from the group consisting of hydroxyl groups, carboxyl groups, amino groups, and epoxy groups. Particularly preferably, the reactive silicone has an amino group and / or an epoxy group. Note that the epoxy group may be included in the form of a glycidyl group.

[0065] The reactive silicone is not particularly limited as long as it is a silicone having the above-mentioned reactive group, but examples include amino-modified silicone, epoxy-modified silicone, carboxy-modified silicone, (meth)acrylic-modified ((meth)acryloyl-modified) silicone, carbinol-modified silicone, silanol-modified silicone, etc. Among these, amino-modified silicone and / or epoxy-modified silicone are preferred as the reactive silicone because they have excellent reactivity with the epoxy group contained in the block copolymer. The amino-modified silicone is not particularly limited, but polydimethylsiloxane having a 3-aminopropyl group is preferred, and polydimethylsiloxane having a 3-aminopropyl group at both ends is more preferred. The epoxy-modified silicone is not particularly limited, but polydimethylsiloxane having a glycidyl ether group is preferred, and polydimethylsiloxane having a glycidyl ether group at both ends is more preferred. The above-mentioned reactive silicone can be used alone or in combination of two or more types. When two or more types are used, the content of the reactive silicone represents the total amount of these.

[0066] In one embodiment, the silicone compound constituting the surface lubrication layer may be a reactive silicone. That is, the silicone compound contained in the surface lubrication layer may consist substantially only of reactive silicone. Here, "a form in which the silicone compound contained in the surface lubrication layer consists substantially only of reactive silicone" means a form in which, at least intentionally, silicone compounds other than reactive silicone (i.e., non-reactive silicone) are not contained in the surface lubrication layer. Therefore, a surface lubrication layer that inevitably contains trace amounts of silicone compounds other than reactive silicone due to raw materials, manufacturing methods, etc., is included in the above form. In other words, the above form refers to a form in which the silicone compound contained in the surface lubrication layer does not contain any silicone compounds other than reactive silicone.

[0067] In a preferred embodiment, the silicone compound constituting the surface lubrication layer further includes a non-reactive silicone in addition to the reactive silicone. That is, it is preferable that the silicone compound included in the surface lubrication layer includes both a reactive silicone and a non-reactive silicone. With such a configuration, the sliding properties in a wet state are further improved, resulting in a dilator with superior operability. Furthermore, this configuration also has the advantage of easily suppressing stickiness (tackiness) during the drying process after wetting. Here, "non-reactive silicone" refers to a silicone compound that does not have reactive groups.

[0068] The non-reactive silicone is not particularly limited as long as it does not have the above-mentioned reactive group, but examples include dimethyl silicone, methylphenyl silicone, and methylhydrogen silicone. Among these, dimethyl silicone is preferred as the non-reactive silicone. The above-mentioned non-reactive silicone can be used alone or in combination of two or more types. When two or more types are used, the content of the non-reactive silicone represents the total amount of these types.

[0069] The above-mentioned silicone compound may be a commercially available product or a synthetic product. Examples of commercially available reactive silicones that can be used include KF-393, KF-859, KF-860, KF-864, KF-865, KF-868, KF-880, KF-8002, KF-8004, KF-8005, KF-8008, KF-8012, X-22-343, KF-101, KF-1001, X-22-2000, X-22-4039, X-22-4015, X-22-3701E, X-22-4741, KF-1002, X-22-163, and X-22-164 (manufactured by Shin-Etsu Chemical Co., Ltd.). In addition, commercially available non-reactive silicones such as SH-200, SH510, SH550, SH710 (manufactured by Toray Dow Corning Co., Ltd.), KF-96, KF-96H, KF-965, KF-968, KF-50, KF-53, and KF-54 (manufactured by Shin-Etsu Chemical Co., Ltd.) can be used.

[0070] Furthermore, as for the synthesis method, known methods for synthesizing silicone compounds can be used as is or modified as appropriate. Examples of methods for synthesizing reactive silicones include reacting an amino group-containing silane with a polydiorganosiloxane containing a silanol group, and reacting an epoxy group-containing silane with a polydiorganosiloxane containing a silanol group. The reaction between these silane compounds having reactive groups and polydiorganosiloxanes containing silanol groups may be carried out by heating and stirring these compounds with a solvent as needed. In this case, it is preferable to carry out the reaction so that the amino group-containing silane / epoxy group-containing silane is 1 to 5% by mass and the polydiorganosiloxane containing a silanol group is 95 to 99% by mass (total 100% by mass).

[0071] Examples of the above amino group-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.

[0072] Examples of the epoxy group-containing silanes mentioned above include γ-glycidoxypropyltrimethoxysilane, γ-glycidoxypropylmethyldimethoxysilane, β-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, β-(3,4-epoxycyclohexyl)ethylmethyldimethoxysilane, β-(3,4-epoxycyclohexyl)ethyltriethoxysilane, and β-(3,4-epoxycyclohexyl)ethylmethyldiethoxysilane.

[0073] Examples of organic groups that bond to the silicon atom of the silanol group in the polydiorganosiloxane containing the silanol group include alkyl groups such as methyl groups, phenyl groups, and vinyl groups. From the viewpoint of ease of synthesis of the polydiorganosiloxane, the organic group is preferably a methyl group or a phenyl group, and more preferably a methyl group. Specific examples of polydiorganosiloxanes containing a silanol group include polydimethylsiloxane in which one end is occluded with a silanol group and the other end is occluded with a trimethylsilyl group, polydimethylsiloxane in which both ends are occluded with silanol groups, and polymethylphenylsiloxane in which both ends are occluded with silanol groups.

[0074] It is preferable that the mass ratio of the silicone compound to the block copolymer in the surface lubrication layer (silicone compound:block copolymer) is 0.1 to 1:1. That is, it is preferable that the surface lubrication layer contains the silicone compound and the block copolymer in a mass ratio of 0.1 to 1:1 (silicone compound:block copolymer). Furthermore, it is more preferable that the mass ratio of the silicone compound to the block copolymer in the surface lubrication layer is greater than 0.1 and less than 1:1, and particularly preferable that it is greater than 0.1 and 0.8 or less:1. By setting the mass ratio of the silicone compound to the block copolymer in the surface lubrication layer within the above range, the lubricity of the surface lubrication layer can be made even better.

[0075] In this specification, "silicone compound content" refers to the total amount of both reactive and non-reactive silicones if the silicone compound includes both reactive and non-reactive silicones. Furthermore, the "silicone compound content" refers to the total mass of the silicone compound components (the total mass of unreacted components and components reacted with the block copolymer). In this specification, the reactive silicone content refers to the total mass of unreacted components and components reacted with the block copolymer.

[0076] When the surface lubrication layer contains reactive silicone and non-reactive silicone as silicone compounds, the mass ratio of these is not particularly limited. However, the mass ratio of reactive silicone to non-reactive silicone (reactive silicone:non-reactive silicone) in the surface lubrication layer is preferably 0.01 to 1:1, more preferably 0.03 to 1:1, even more preferably 0.05 to 1:1, even more preferably 0.1 to 1:1, particularly preferably 0.5 to 0.8:1, and most preferably 0.6 to 0.7:1. By using the above mass ratio, phase separation with the block copolymer is more effectively suppressed, and a uniform film is easily formed. Furthermore, while ensuring sufficient lubricity (sliding properties) of the surface lubrication layer, the crosslinking of the block copolymer is sufficiently advanced without excessive advancement (crosslinking can be moderately promoted). Therefore, the lubricity and durability of the resulting surface lubrication layer can be fully exhibited.

[0077] (Other components) The surface lubrication layer may contain other components in addition to the block copolymer, polyvinyl chloride, and silicone compound. The other components are not particularly limited and can be appropriately selected, for example, depending on the application of the dilator.

[0078] (Sliding Resistance Value) The surface lubrication layer of the dilator according to one embodiment of the present invention preferably has a sliding resistance value of 1 gf or more and 30 gf or less, more preferably 3 gf or more and 25 gf or less, even more preferably 5 gf or more and 20 gf or less, particularly preferably 10 gf or more and 20 gf or less, and most preferably 10 gf or more and 15 gf or less. When the sliding resistance value of the surface lubrication layer is within the above range, the sliding properties of the surface lubrication layer are sufficient, and the operability of the dilator is further improved. The above sliding resistance value is measured by the method described in [Evaluation of Sliding Properties and Durability] of the Examples.

[0079] [Method for Manufacturing a Dilator] The surface lubrication layer of the dilator may be formed by any method that can form a film on the substrate layer comprising a block copolymer and, if necessary, at least one selected from the group consisting of polyvinyl chloride and silicone compounds. However, it is preferable that the layer be formed by applying a coating liquid comprising a block copolymer, a solvent, and, if necessary, at least one selected from the group consisting of polyvinyl chloride and silicone compounds onto the substrate layer.

[0080] Accordingly, another aspect of the present invention provides a method for manufacturing a dilator comprising a substrate layer containing a polyolefin resin and a contrast agent, and a surface lubricating layer supported on at least a portion of the substrate layer, the method comprising preparing a coating liquid containing a block copolymer having constituent units (A) derived from a reactive monomer having an epoxy group and constituent units (B) derived from a hydrophilic monomer, a solvent, and optionally at least one selected from the group consisting of polyvinyl chloride and silicone compounds, and applying the coating liquid onto the substrate layer. The method for manufacturing a dilator having the above configuration will hereinafter also be referred to as "the manufacturing method according to the present invention" or "the manufacturing method".

[0081] The method for producing a dilator according to the present invention includes preparing a coating solution comprising a block copolymer having constituent units (A) derived from a reactive monomer having an epoxy group and constituent units (B) derived from a hydrophilic monomer, a solvent, and optionally at least one selected from the group consisting of polyvinyl chloride and silicone compounds ((I) preparation step); and applying the coating solution onto a substrate layer ((II) coating step). In this way, by using a solution comprising a block copolymer and optionally at least one selected from the group consisting of polyvinyl chloride and silicone compounds as a coating solution, a dilator having a surface lubricating layer that exhibits excellent lubrication retention can be obtained.

[0082] A dilator manufactured by the method according to the present invention has a structure in which a surface lubricating layer is supported on a substrate layer by applying a coating liquid containing a block copolymer that forms a surface lubricating layer and, optionally, at least one selected from the group consisting of polyvinyl chloride and silicone compounds, onto a substrate layer. In the coating liquid, the block copolymer is dissolved in the solvent (the block copolymer is uniformly mixed in the coating liquid), so the block copolymer can form a uniform surface lubricating layer. Even when the coating liquid contains, in addition to the block copolymer, at least one selected from the group consisting of polyvinyl chloride and silicone compounds, the block copolymer and at least one selected from the group consisting of polyvinyl chloride and silicone compounds are dissolved in the solvent in the coating liquid (the block copolymer and at least one selected from the group consisting of polyvinyl chloride and silicone compounds are uniformly mixed in the coating liquid). Therefore, the block copolymer and at least one selected from the group consisting of polyvinyl chloride and silicone compounds can form a uniform surface lubricating layer without forming a phase separation structure. Accordingly, the surface lubricating layer of the dilator manufactured by the above manufacturing method has excellent lubricity.

[0083] In the method for producing a dilator according to the present invention, terms such as block copolymer, polyvinyl chloride, and silicone compound are the same as those described in the [Dilator] section above, so their explanation is omitted here.

[0084] In the dilator manufacturing method according to the present invention, after step (II) above, further steps such as a drying and / or heat treatment step ((III) drying / heat treatment step) and a washing step ((IV) washing step) may be performed as needed. Of these, it is preferable to perform at least a further drying / heat treatment step (III) after step (II) above. Each of the above steps (I) to (IV) will be described below.

[0085] (I) Preparation Step In this step, a coating solution is prepared, comprising a block copolymer, a solvent, and optionally at least one selected from the group consisting of polyvinyl chloride and a silicone compound. Here, in this step, the coating solution may be prepared by mixing the block copolymer, the solvent, and optionally at least one selected from the group consisting of polyvinyl chloride and a silicone compound. Alternatively, a coating solution comprising a block copolymer, a solvent, and optionally at least one selected from the group consisting of polyvinyl chloride and a silicone compound may be purchased and used.

[0086] In the following, preferred embodiments of preparing a coating solution will be described in detail, which involve mixing a block copolymer, a solvent, and, if necessary, at least one selected from the group consisting of polyvinyl chloride and a silicone compound.

[0087] (Preparation of coating solution) The coating solution is prepared using the block copolymer, solvent, and, if necessary, at least one selected from the group consisting of polyvinyl chloride and silicone compounds. The order and method of adding the block copolymer, solvent, and, if necessary, at least one selected from the group consisting of polyvinyl chloride and silicone compounds are not particularly limited. Each of the above components may be added together or separately, in stages or sequentially.

[0088] Furthermore, there are no particular restrictions on the method of mixing each component, and known methods can be used. One method for preparing the coating solution is to add the block copolymer to the solvent. If the coating solution contains at least one selected from the group consisting of polyvinyl chloride and silicone compounds, methods include adding at least one selected from the group consisting of polyvinyl chloride and silicone compounds to the solvent, followed by the addition of the block copolymer; adding the block copolymer to the solvent, followed by the addition of at least one selected from the group consisting of polyvinyl chloride and silicone compounds; or adding the block copolymer and at least one selected from the group consisting of polyvinyl chloride and silicone compounds to the solvent all at once.

[0089] If the coating solution contains at least one selected from the group consisting of polyvinyl chloride and silicone compounds, it is preferable to add at least one selected from the group consisting of polyvinyl chloride and silicone compounds to the solvent first, and then add the block copolymer, from the viewpoint of easily preparing a homogeneous solution (coating solution). This addition may be carried out while stirring if necessary. More specifically, it is preferable to mix the solvent and at least one selected from the group consisting of polyvinyl chloride and silicone compounds to obtain a solution, and then further mix in the block copolymer. By adopting this configuration, the formation of a phase separation structure between the block copolymer and at least one selected from the group consisting of polyvinyl chloride and silicone compounds becomes less likely, and a more uniform surface lubrication layer can be formed. As a result, the lubricity of the surface lubrication layer can be improved.

[0090] The solvent used in preparing the coating solution is not particularly limited as long as it can dissolve the block copolymer (and other components, if any) in addition to the block copolymer. Furthermore, if the coating solution contains, in addition to the block copolymer, at least one selected from the group consisting of polyvinyl chloride and silicone compounds, the solvent should be appropriately selected depending on the type of block copolymer and at least one selected from the group consisting of polyvinyl chloride and silicone compounds (and other components, if any). Specific examples of solvents for the coating solution include, for example, alcoholic solvents such as methanol, ethanol, isopropyl alcohol, 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). Note that the above-mentioned solvents may be used individually or in combination of two or more (in the form of a mixed solvent).

[0091] In particular, from the viewpoint of excellent solubility, the solvent preferably contains at least one selected from the group consisting of methanol, ethanol, isopropyl alcohol, butanol, ethylene glycol; acetone, methyl ethyl ketone, cyclohexanone; ethyl acetate, butyl acetate; tetrahydrofuran (THF), butyl ether, dioxane; hexane, heptane; benzene, toluene; dimethyl sulfoxide (DMSO); and N,N-dimethylformamide (DMF). It is more preferably that the solvent contains at least one selected from the group consisting of acetone, methyl ethyl ketone, cyclohexanone, tetrahydrofuran, butyl ether, dioxane, and N,N-dimethylformamide, and even more preferably that it contains tetrahydrofuran and / or N,N-dimethylformamide.

[0092] The concentration of the block copolymer in the coating solution is not particularly limited. From the viewpoint of further improving the applicability, 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 resulting surface lubricating layer can be fully exhibited. Furthermore, a uniform surface lubricating layer of the desired thickness can be easily obtained with a single coating, and the viscosity of the solution will be within an appropriate range, which is preferable in terms of workability (e.g., ease of coating) and production efficiency. However, even if it is outside the above range, it can still be used as long as it does not affect the effects of the present invention.

[0093] When the coating solution contains polyvinyl chloride, the concentration of polyvinyl chloride in the coating solution is not particularly limited. From the viewpoint of the lubricity (sliding properties) and durability (sliding durability) of the surface lubrication layer, it is preferable to add polyvinyl chloride to some extent. From the above point, the concentration of polyvinyl chloride in the coating solution is preferably 0.004% by mass or more and 4.0% by mass or less, more preferably 0.01% by mass or more and 2.0% by mass or less, even more preferably 0.05% by mass or more and 1.0% by mass or less, and particularly preferably 0.05% by mass or more and 0.5% by mass or less. If the concentration of polyvinyl chloride is within the above range, the lubricity (sliding properties) of the surface lubrication layer is sufficiently ensured, and the crosslinking of the block copolymer is sufficiently advanced without excessive advancement (crosslinking can be moderately promoted). Therefore, the lubricity and durability of the resulting surface lubrication layer can be fully exhibited. As a result, a dilator with superior operability can be obtained. However, even if it is outside the above range, it is still perfectly usable as long as it does not affect the effects of the present invention.

[0094] Furthermore, the mixing ratio of the block copolymer and polyvinyl chloride in the coating solution is similar to the preferred content ratio (mass ratio) of the block copolymer and polyvinyl chloride present in the surface lubrication layer. If the mass ratio of the block copolymer and polyvinyl chloride is within the above range, the durability and lubricity of the resulting surface lubrication layer can be fully exhibited. As a result, a dilator with superior operability can be obtained.

[0095] When the coating liquid contains a silicone compound, the concentration of the silicone compound in the coating liquid is not particularly limited, but is preferably 0.01 to 15% by mass, more preferably 0.1 to 10% by mass, even more preferably 0.5 to 5% by mass, and particularly preferably 0.5% by mass or more and less than 5% by mass. If the concentration of the silicone compound is within the above range, the lubricity of the surface lubrication layer can be sufficiently exhibited. As a result, a dilator with superior operability can be obtained. However, even if the concentration is outside the above range, it is still perfectly usable as long as it does not affect the effects of the present invention.

[0096] Furthermore, the preferred mixing ratio (mass ratio) of block copolymer and silicone compound in the coating liquid is the same as the preferred content ratio (mass ratio) of block copolymer and silicone compound present in the surface lubrication layer. If the mass ratio of block copolymer and silicone compound in the coating liquid is within the above range, the durability and lubricity of the surface lubrication layer can be fully exhibited. As a result, a dilator with superior operability can be obtained.

[0097] Furthermore, when using reactive and non-reactive silicones as silicone compounds, the preferred mixing ratio (mass ratio) of reactive and non-reactive silicones in the coating solution is the same as the preferred mass ratio of reactive and non-reactive silicones in the surface lubrication layer. If the mass ratio of reactive and non-reactive silicones in the coating solution is within the above range, the lubricity (sliding properties) of the surface lubrication layer is sufficiently ensured, while the crosslinking of the block copolymer is sufficiently advanced without excessive advancement (crosslinking can be moderately promoted). Therefore, the lubricity and durability of the resulting surface lubrication layer can be fully exhibited. As a result, a dilator with superior operability can be obtained.

[0098] (II) Coating process In this process, the coating liquid prepared in (I) preparation process is applied to the substrate layer to form a coating film (coated layer) on the substrate layer.

[0099] The base layer comprises a polyolefin resin and a contrast agent. The polyolefin resin and contrast agent are the same as those described in the section on <Base Layer (Base Material)> above, so a detailed explanation is omitted here.

[0100] The method for applying the coating liquid to the surface of the substrate layer is not particularly limited, and conventionally known methods such as coating / printing, immersion (dipping method, dip coating method), spraying method, spin coating method, mixed solution impregnation sponge coating method, bar coating method, die coating method, reverse coating method, comma coating method, gravure coating method, and doctor knife method can be applied. Of these, the immersion method (dipping method, dip coating method) is preferred.

[0101] Furthermore, when forming a surface lubrication layer on only a portion of the base layer, the surface lubrication layer can be formed on the desired surface portion of the base layer by immersing only a portion of the base layer in the coating liquid and coating that portion of the base layer with the coating liquid.

[0102] When using the immersion method, the lifting speed when removing the substrate layer after immersion in the coating solution is not particularly limited, but is preferably 1 mm / sec to 30 mm / sec, more preferably 2 mm / sec to 20 mm / sec, and even more preferably 2.5 mm / sec to 15 mm / sec. By keeping the lifting speed within the above range, a desired amount of coating solution can be applied to the surface of the substrate layer.

[0103] In the coating process according to one embodiment of the present invention, it is preferable to immerse only the leading edge of the substrate layer in the coating liquid. Here, the leading edge of the substrate layer is the same as the leading edge of the dilator described later in [Shape and Use of the Dilator], so the explanation is omitted.

[0104] The amount of coating liquid applied is preferably such that the thickness (dry film thickness) of the resulting film (surface lubrication 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 application amount results in a film (surface lubrication layer) thickness of 0.1 μm or more, sufficient durability of the resulting film (surface lubrication layer) can be achieved. Furthermore, if the application amount results in a film (surface lubrication layer) thickness of 10 μm or less, the surface of the film (surface lubrication layer) becomes less sticky, making handling during manufacturing easier.

[0105] (III) Drying / Heat Treatment Step In the dilator manufacturing method according to the present invention, if necessary, after applying the coating liquid to the substrate layer in the (II) coating step above to form a coating film (coating layer), a drying step and / or a heat treatment step may be performed. It is preferable to perform a drying step and / or a heat treatment step for the purpose of removing the solvent and forming a strong surface lubricating layer, and it is more preferable to perform a drying step and a heat treatment step.

[0106] Here, "drying treatment" and "heating treatment" are not strictly distinguished, but for the sake of explanation, "drying treatment" refers to keeping the substrate layer coated with the above coating liquid at or below room temperature (20-30°C), and "heating treatment" refers to keeping it at a temperature above room temperature (20-30°C).

[0107] The conditions during drying or heat treatment are not particularly limited, as long as they allow for the formation of a surface lubricating layer containing the block copolymer on the substrate layer.

[0108] The temperature for drying or heat treatment is not particularly limited, but is preferably 10 to 200°C. That is, it is more preferable to maintain the coating layer at 10 to 200°C after applying the block copolymer solution to the substrate layer (after forming the coating layer). By maintaining it at such a temperature, the crosslinking or polymerization of the block copolymer is effectively promoted, and a strong coating layer (surface lubrication layer) is formed. As a result, high lubricity (surface lubricity) can be maintained for a longer period of time. In addition, by maintaining it at such a temperature, it is possible to suppress the excessive progression of the above crosslinking or polymerization. As a result, the decrease in swelling caused by the surface lubrication layer becoming too hard can be suppressed, and as a result, good lubricity (surface lubricity) can be maintained.

[0109] Furthermore, after applying the block copolymer solution onto the substrate layer (after forming the coating layer), it is more preferable to maintain the coating layer at 200°C or below, even more preferable to maintain it at 20 to 150°C, particularly preferable to maintain it at 20 to 135°C, and most preferable to maintain it at 20 to 130°C. By maintaining it at such temperatures, the crosslinking reaction is further promoted, and a surface lubricating layer with higher durability can be formed. In addition, the surface lubricating layer can exhibit excellent lubricity. In particular, by keeping it at 150°C or below, excessive crosslinking or polymerization of the block copolymer can be suppressed. In addition, a decrease in the hydrophilicity of the constituent units (B) of the block copolymer can be prevented or suppressed. Therefore, a decrease in swelling caused by the surface lubricating layer becoming too hard can be suppressed, and the control of lubricity can be made easier. Note that the above temperatures may be changed during the drying or heat treatment.

[0110] Furthermore, while there are no particular restrictions on the drying or heat treatment time, it is preferably 15 minutes to 30 hours, more preferably 20 minutes to 25 hours, and most preferably 30 minutes to 12 hours. By using such a time, crosslinking or polymerization in the block copolymer is effectively promoted, and a strong coating layer (surface lubrication layer) is formed. As a result, high lubricity (surface lubricity) can be maintained for a longer period of time. Also, by using such a time, it is possible to suppress the excessive progression of the above crosslinking or polymerization. As a result, a decrease in swelling caused by the surface lubrication layer becoming too hard can be suppressed, and as a result, good lubricity (surface lubricity) can be maintained. In particular, by setting the heat treatment time to 25 hours (especially 15 hours) or less, a decrease in the hydrophilicity of the constituent units (B) of the block copolymer can be prevented and suppressed, making it easier to control the lubricity. Note that the drying or heat treatment time may be shorter, for example, 10 minutes to 5 hours or 15 minutes to 3 hours. In this way, damage to the hydrophilic groups within the constituent unit (B) (decrease in the hydrophilicity of the constituent unit (B) of the block copolymer) can be further suppressed over a short period, allowing the surface lubrication layer to exhibit better lubrication. Furthermore, since it is possible to form a surface lubrication layer with excellent durability at low temperatures, this is also preferable from an energy cost standpoint during the manufacturing of the dilator.

[0111] In this process, from the viewpoint of particularly effectively (efficiently) promoting the crosslinking or polymerization of the block copolymer, it is preferable to perform a heat treatment after the drying treatment. By going through drying and heat treatment in this way, the solvent is removed (i.e., the block copolymer and polymer material are in a state where they can easily come into contact), and the effect of promoting the crosslinking or polymerization of the block copolymer by the polymer material is further improved.

[0112] The conditions for drying and heat treatment (temperature, time, etc.) are not particularly limited, but from the viewpoint of efficiently manufacturing dilators, it is preferable to perform a drying treatment at 10-30°C for 15 minutes to 5 hours, followed by a heat treatment at 40-200°C for 30 minutes to 10 hours. Furthermore, from the same viewpoint, it is even more preferable to perform a drying treatment at 15-30°C for 20 minutes to 3 hours, followed by a heat treatment at 45-150°C for 45 minutes to 8 hours. Under these conditions, it is possible to manufacture dilators with a surface lubrication layer that has excellent durability. In addition, a further drying treatment may be performed after the above heat treatment.

[0113] Under the conditions described above (temperature, time, etc.), a strong surface lubricating layer (coating layer) can be supported on the surface of the substrate layer.

[0114] For example, an oven or a vacuum dryer can be used as the means (apparatus) for the above-mentioned heat treatment and drying processes, but in the case of natural drying, no special drying means (apparatus) is required.

[0115] [Shape and Use of the Dilator] The shape and use of the dilator 10 according to one embodiment of the present invention will be described below with reference to Figure 2. In addition to the dilator 10 according to one embodiment, Figure 2 also shows a sheath 20, which is included in the sheath assembly 30, which is another embodiment of the present invention. The sheath 20 and the sheath assembly 30 will be described later.

[0116] A dilator 10 according to one embodiment of the present invention comprises a dilator body 11 made of a tubular body that can be inserted into a sheath tube 21 of a sheath 20 (described later), and a dilator hub 12 configured to be connectable to a hub 22. Here, the dilator body 11 is made of the base material layer 1 described above. That is, the base material layer constitutes a tubular body that can be inserted into the sheath tube 21. In addition, a surface lubrication layer 2 is supported on at least a part of the surface of the dilator body 11.

[0117] The dilator 10 can be used to prevent the sheath tube 21 from bending or to enlarge the puncture site when inserting the sheath tube 21 into a blood vessel. The dilator body 11 and the dilator hub 12 have a guidewire lumen 13 that extends in the axial direction. The guidewire lumen 13 is used to insert a mini guidewire that is already inserted in the body when inserting the sheath assembly 30, which is a combination of the dilator 10 and the sheath 20, into the body. The sheath assembly 30, which is a combination of the dilator 10 and the sheath 20, is inserted into the body via the mini guidewire.

[0118] In one embodiment, the diameter of the lumen (guide wire lumen 13) of the dilator 10 is not particularly limited, but the inner diameter of the tip of the dilator 10 (the diameter of the guide wire lumen 13 at the tip) is preferably 5.0 mm or less, more preferably 2.5 mm or less, even more preferably 2.0 mm or less, even more preferably 1.5 mm or less, particularly preferably 1.0 mm or less, and most preferably 0.5 mm or less. Also, the inner diameter of the tip of the dilator is not particularly limited, but it is preferably 0.01 mm or more, more preferably 0.05 mm or more, and even more preferably 0.1 mm or more. Having the inner diameter of the tip of the dilator 10 within the above range is preferable because it facilitates operation using a relatively thin guide wire and reduces backflow of blood and other fluids from blood vessels.

[0119] The dilator body 11 is inserted through the lumen 26 of the sheath tube 21. When the sheath 20 and the dilator 10 are connected, the tip of the dilator body 11 protrudes by a predetermined length from the tip opening 27 of the sheath tube 21. This portion of the dilator body 11 that protrudes from the tip opening 27 of the sheath tube 21 is referred to as the tip of the dilator 10.

[0120] In procedures using the sheath assembly 30, because the sheath assembly 30 has the structure described above, the tip of the dilator 10 mainly comes into contact with the inside of the blood vessel. Conventional sheath assemblies are difficult to use when passing through narrowed or bent parts of blood vessels, and their operability is not sufficient. This is thought to be due to the frictional resistance caused by the contact between the inside of the blood vessel and mainly the tip of the dilator 10 when passing through these areas. The dilator 10 according to the present invention has a predetermined surface lubricating layer 2 on its surface that has excellent sliding properties and durability, so that the frictional resistance between the dilator 10 and the inside of the blood vessel can be reduced. As a result, the difficulty in passing through narrowed or bent parts of blood vessels is improved, and the operability of the dilator 10 and the sheath assembly 30 is improved.

[0121] The dilator 10 and sheath assembly 30 according to the present invention can be used particularly suitably in a crossover approach for treating lesions in the lower limb arteries. A crossover approach is a technique in which the sheath assembly 30 is inserted into a lower limb artery opposite to the lower limb artery where the lesion is located, passed through the artery, and reached the lesion or just before it. For example, using a crossover approach, if there is a lesion in the femoral artery of the right leg, the femoral artery of the left leg is punctured, and the sheath assembly 30, consisting of the dilator 10 and sheath 20, is inserted from the left femoral artery, crossing the aortoiliac artery bifurcation (hereinafter referred to as "crossing the mountain"), and reaching the lesion in the right femoral artery or just before it. In this crossover approach, when crossing a ridge, the tip of the dilator 10 inevitably comes into contact with the blood vessel wall of the artery opposite to the artery from which the sheath assembly 30 was punctured (for example, the left artery if the right artery is punctured). However, with conventional dilators and sheath assemblies, this contact between the tip and the blood vessel wall generates significant frictional resistance. As a result, conventional dilators and sheath assemblies have the problem of being extremely difficult to operate in the crossover approach. For example, with conventional dilators, when crossing a ridge, the aforementioned frictional resistance causes the dilator to stop midway (for example, near the common iliac artery), making it difficult to push it distally toward the external iliac artery. Furthermore, if strong force is applied, the dilator may bend (for example, into a V-shape), further reducing its operability. On the other hand, the dilator 10 and sheath assembly 30 according to the present invention have a predetermined surface lubrication layer with excellent sliding properties and durability, thereby suppressing the occurrence of the above-mentioned problems in the crossover approach. For example, even if the tip of the dilator 10 comes into contact with the blood vessel wall when crossing a ridge, the frictional resistance between them is small, so the dilator 10, etc. does not stop midway (for example, near the common iliac artery), and the sheath assembly 30 can be easily pushed along the arc-shaped trajectory from the common iliac artery toward the peripheral external iliac artery. Furthermore, since it is not necessary to push with strong force, the dilator 10, etc. is less likely to break.For these reasons, the dilator 10 and sheath assembly 30 according to the present invention can be particularly suitably used in a crossover approach. Furthermore, a crossover approach can also be used to treat lesions in the common iliac artery.

[0122] In the dilator 10 according to one embodiment of the present invention, the length of the tip portion depends on the combination of the dilator 10 and the sheath tube 21, and may be 1 mm to 1000 mm, 5 mm to 500 mm, 10 mm to 100 mm, or 15 mm to 50 mm in the axial direction from the tip of the dilator 10.

[0123] In the dilator 10 according to one embodiment of the present invention, the surface lubrication layer 2 is supported on at least a portion of the surface of the base material layer 1. However, from the viewpoint of further improving the operability of the dilator 10 and the sheath assembly 30, it is preferable that the surface lubrication layer 2 is supported on the base material layer 1 at least at the tip of the dilator 10, and more preferably that it is supported only on the base material layer 1 at the tip of the dilator 10.

[0124] Furthermore, the dilator body 11 may have a tapered portion 14 that narrows towards the tip. The portion of the dilator body 11 located closer to the base end than the tapered portion 14 extends axially with a substantially constant outer diameter. The axial length of the tapered portion 14 of the dilator body 11 is not particularly limited, but for example, it is 10 to 25 mm axially from the tip. When the sheath 20 and the dilator 10 are connected, the tip of the dilator body 11 is connected to the tip of the sheath tube 21 of the sheath 20 with virtually no step difference.

[0125] [Sheath Assembly] Another embodiment of the present invention is a sheath assembly 30 comprising the dilator 10 according to the present invention as described above. As shown in Figure 2, the sheath assembly 30 according to another embodiment of the present invention comprises the dilator 10 according to the present invention and a sheath 20. Hereinafter, the shape and usage method of the sheath assembly 30 and the sheath 20 included in the sheath assembly 30 according to one embodiment of the present invention will be described with reference to Figure 2. In the following description, the hand-operated end side (hub 22 side) of the sheath 20 will be referred to as the "proximal end side," and the side inserted into the body cavity will be referred to as the "tip end side."

[0126] (Sheath) The sheath 20 can be used to introduce the dilator body 11 of the dilator 10 and various medical devices (catheter devices, guide wires, etc.) into the lumen of a living body via the lumen 26 of the sheath tube 21. The sheath 20 according to this embodiment can be used with stent grafts, thrombus aspiration, etc.

[0127] As shown in Figure 2, the sheath 20 comprises a sheath tube 21, a hub 22 attached to the base end of the sheath tube 21, and a common port 23 provided inside the hub 22.

[0128] The sheath tube 21 is a tubular member that is inserted percutaneously into a biological lumen, through which medical devices such as the dilator body 11 and catheters can be inserted, and which has a lumen 26 through which liquid can flow. The sheath tube 21 can be made to be about 3 to 10 Fr, with an inner diameter of 2 to 3 mm and an outer diameter of 2.5 to 3.5 mm.

[0129] As constituent materials for the sheath tube 21, for example, polyolefin resins (e.g., polyethylene, polypropylene, polybutene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, ionomer, or mixtures of two or more thereof), polyolefin elastomers, crosslinked polyolefins, polyvinyl chloride, polyamide resins, polyamide elastomers, polyester resins, polyester elastomers, polyurethane resins, polyurethane elastomers, fluororesins (e.g., polytetrafluoroethylene, tetrafluoroethylene-ethylene copolymer, etc.), polycarbonate resins, polystyrene, polyacetal resins, polyimide resins, polyetherimide, polyetheretherketone, and other polymer materials, or mixtures thereof, can be used.

[0130] The hub 22 is connected to the proximal end of the sheath tube 21. In this embodiment, the hub 22 is fitted with a hemostatic valve that communicates with the proximal end and has a common port 23 that communicates with the inside of the sheath tube 21. One end of a flexible tube 24, for example made of polyvinyl chloride, is liquid-tightly connected to the common port 23. The other end of the tube 24 is fitted with, for example, a three-way stopcock 25. A liquid, such as physiological saline, is injected into the sheath 20 through the tube 24 from the port of the three-way stopcock 25 for priming or other purposes.

[0131] The constituent material of the hub 22 is not particularly limited, but a hard material such as a hard resin is preferred. Specific examples of hard resins include polyethylene, polyolefin resins such as polypropylene, polyamide resins, polycarbonate resins, and polystyrene.

[0132] <Treatment Method Using Dilator and Sheath Assembly> Next, an overview of the treatment method using the dilator 10 and sheath assembly 30 according to this embodiment will be described.

[0133] First, a guide wire is inserted into a designated location in the skin using an introduction needle or the like, and the guide wire is inserted into a blood vessel, for example, through the lumen of the introduction needle. The introduction needle is then withdrawn from the lumen while the guide wire remains in place. Then, saline solution is introduced from the tube 24 to the inlet of the common port 23 through a three-way stopcock 25 into the sheath assembly 30, in which the dilator 10 is inserted into the sheath 20 through the valve body of the hemostatic valve or the center of the check valve of the Y connector.

[0134] Next, the sheath assembly 30 is inserted while guiding the lumen of the dilator 10 (guidewire lumen 13) along the guidewire placed in the biological lumen. Subsequently, while confirming the tip of the sheath assembly 30 (dilator 10) under X-ray fluoroscopy, the tip of the sheath assembly 30 is advanced to just before the target site (lesion site). For example, in the case of a crossover approach, the sheath assembly 30 is advanced over the ridge of the punctured lower limb artery and to the target site (lesion site) or just before it in the lower limb artery on the opposite side of the punctured lower limb artery. When crossing the ridge, the sheath assembly 30 is advanced by pushing it from the common iliac artery side toward the peripheral external iliac artery side while the tip of the dilator 10 is in contact with the vessel wall of the common iliac artery on the opposite side of the punctured lower limb artery. After the tip of the sheath assembly 30 reaches the target site (lesion site) or just before it, the guidewire and dilator 10 are removed from the sheath 20 while the sheath 20 remains in the biological lumen. This allows the sheath 20 to function as a passage connecting the outside of the body and the inside of the blood vessel, enabling the insertion of medical devices such as stent delivery catheters and balloon catheters into the blood vessel and the performance of various procedures.

[0135] The effects of the present invention will be explained using the following examples and comparative examples. However, the technical scope of the present invention is not limited to the following examples. In the following examples, unless otherwise specified, the operations were carried out at room temperature (25°C). Unless otherwise specified, "%" and "parts" mean "mass%" and "parts by mass," respectively.

[0136] Synthesis Example 1 The following reaction was carried out to produce block copolymer (1).

[0137]

[0138] 72.3 g of adipic acid dichloride at 50°C was mixed dropwise with 29.7 g of triethylene glycol, and the hydrochloric acid was removed under reduced pressure at 50°C for 3 hours to obtain an oligoester. Next, 4.5 g of methyl ethyl ketone was added to 22.5 g of the obtained oligoester, and this was added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of dioctyl phosphate as a surfactant, and 120 g of water, and the mixture was reacted at -5°C for 20 minutes. The resulting product was washed with water and methanol, and then dried to obtain a polyperoxide (PPO) having multiple peroxide groups in its molecule.

[0139] Next, 0.5 g of PPO, 9.5 g of glycidyl methacrylate (GMA), and 30 g of benzene were used as solvents and polymerized at 80°C for 2 hours under reduced pressure with stirring. The reaction product obtained after polymerization was reprecipitated with diethyl ether to obtain polyglycidyl methacrylate (PPO-GMA) having multiple peroxide groups in its molecule.

[0140] Next, 1.0 g of the obtained PPO-GMA (equivalent to 7 mmol of GMA) was charged with 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 reaction product obtained after the reaction was reprecipitated with hexane and recovered to obtain a block copolymer (1) having epoxy groups in the molecule and exhibiting lubricity when wet (constituent unit (A):constituent unit (B) = GMA:DMAA = 1:12 (molar ratio)). Regarding the block copolymer (1) obtained in this way, １ Analysis by 1H-NMR and ATR-IR confirmed the presence of epoxy groups within the molecule. Furthermore, the weight-average molecular weight (Mw) of block copolymer (1), measured by gel permeation chromatography (GPC, polystyrene equivalent), was approximately 1.5 million.

[0141] Example 1 The block copolymer (1) synthesized in Synthesis Example 1 above was dissolved in N,N-dimethylformamide (DMF) to prepare a coating solution (1) so that the final concentration in the coating solution was 4.5% by mass.

[0142] A polypropylene dilator-like tube with a tip inner diameter of 1.0 mm and a tapered section that narrows towards the tip, containing a bismuth compound as a contrast agent, was immersed for 20 mm from the tip in the coating solution (1). The tube was then pulled up at a speed of 5 mm / sec and dried at room temperature (25°C) for 30 minutes to remove the DMF and form a coating film (1) on the tube surface (tube (1)). Furthermore, the tube (1) was stored in an oven at 130°C for 1 hour to heat-treat the coating film (1) (tube (1')). This tube (1') was dried at room temperature (25°C) to prepare a sample (dilator) (1) having a coating layer (surface lubrication layer) (dry film thickness: 1 μm) containing a block copolymer (1) on its surface.

[0143] Example 2 Polyvinyl chloride (manufactured by Fujifilm Wako Pure Chemical Industries, Mw = 50,000 or higher) was dissolved in N,N-dimethylformamide (DMF) to a concentration of 0.1% by mass (Solution (2)). Subsequently, the block copolymer (1) synthesized in Synthesis Example 1 was added to Solution (2) and dissolved to a final concentration of 5.0% by mass in the coating solution to prepare Coating Solution (2). At this time, the final concentration of polyvinyl chloride in the coating solution (2) was 0.095% by mass. A sample (dilator) (2) having a coating layer (surface lubrication layer) was prepared in the same manner as in Example 1, except that Coating Solution (2) was used instead of Coating Solution (1).

[0144] Example 3 A polydimethylsiloxane having 3-aminopropyl groups at both ends (Merck, number average molecular weight: 2,500, reactive silicone (1)), a polydimethylsiloxane having glycidyl ether groups at both ends (Merck, number average molecular weight: 800, reactive silicone (2)), and dimethyl silicone oil (Shin-Etsu Chemical Co., Ltd., KF-96, non-reactive silicone) were mixed in a mass ratio of 35:5:60 (reactive silicone (1): reactive silicone (2): non-reactive silicone), and the resulting mixture was designated as silicone compound (1).

[0145] The silicone compound (1) was dissolved in tetrahydrofuran (THF) to a concentration of 30% by mass, and then diluted with tetrahydrofuran (THF) to a concentration of 1.2% by mass (solution (3)). The block copolymer (1) synthesized in Synthesis Example 1 was added to solution (3) and dissolved to a final concentration of 5.0% by mass in the coating solution to prepare coating solution (3). At this time, the final concentration of silicone compound (1) in coating solution (3) was 1.1% by mass. A sample (dilator) (3) having a coating layer (surface lubrication layer) was prepared in the same manner as in Example 1, except that coating solution (3) was used instead of coating solution (1) and the pulling speed was 10 mm / sec.

[0146] Comparative Example 1 A sample of Comparative Example 1 (Comparative Sample 1) was used, which was a dilator-like tube similar to that in Example 1, with a silicone coating applied to the tip for 20 mm. Comparative Sample 1 was prepared in the same manner as in Example 1, except that the above-mentioned silicone compound (1) was added to tetrahydrofuran (THF) to a final concentration of 5.0% by mass, and a coating solution (4) was used instead of the coating solution (1). The film thickness of the silicone coating was 1 μm, similar to the film thickness of the coating layer (surface lubrication layer) in Examples 1 to 3.

[0147] As a reference example, we also attempted to prepare samples (dilators) with a coating layer (surface lubrication layer) using extruded polypropylene dilator-like tubes without contrast agents, following the same procedure as in Examples 1 to 3. However, in the case of polypropylene dilator-like tubes without contrast agents, the coating layer (surface lubrication layer) was not sufficiently supported on the substrate surface and peeled off easily. This result indicates that the inclusion of a contrast agent allows the surface lubrication layer to be supported with sufficient strength on the substrate surface containing polyolefin resin.

[0148] [Evaluation of sliding properties and durability] The sliding properties and durability of samples (1) to (3) prepared in Examples 1 to 3 above, and comparative sample (1) prepared in Comparative Example 1 were evaluated according to the following method. More specifically, in the following method, the sliding properties and durability of the surface lubricant layer supported on the dilator 10 were evaluated by measuring the sliding resistance value of the portion of the dilator 10 on which the surface lubricant layer 2 is supported (the portion from the tip of the dilator 10 up to 20 mm).

[0149] Referring to Figures 3 and 4, a test apparatus 50 for evaluating the sliding resistance (sliding test) of the dilator according to this embodiment will be described. Figure 3 is a schematic diagram showing the test apparatus 50 for performing a sliding test of the dilator 10 according to this embodiment, showing the dilator 10 sandwiched between a pair of contact members 91 and 92. Figure 4 is a schematic diagram showing the test apparatus 50 for performing a sliding test of the dilator 10 according to this embodiment, showing the dilator 10 separated from the pair of contact members 91 and 92.

[0150] As shown in Figures 3 and 4, the test apparatus 50 has a pair of contact members 91 and 92. The pair of contact members 91 and 92 are configured to move closer to and further apart from each other, and when the pair of contact members 91 and 92 are close together, the dilator 10 can be clamped with a predetermined force. As the test apparatus 50, the DL1000 manufactured by OAKRIVER TECHNOLOGY can be used.

[0151] Next, a method for measuring the sliding resistance of a sample (dilator) 10' as a dilator 10 using the test apparatus 50 will be described. Here, the sample (dilator) 10' corresponds to samples (1) to (3) prepared in Examples 1 to 3, and comparative sample (1) prepared in Comparative Example 1.

[0152] First, each sample 10' was immersed in tap water and placed in a pinch tester (DL1000, manufactured by OAKRIVER TECHNOLOGY) as the test apparatus 50. The pair of contact members 91 and 92 were brought close together and the 20 mm portion from the tip of the sample 10' was clamped with a grip force of 500 gf. For this, the grip pads used as contact members 91 and 92 were made of Shore A60 silicone with a pad height of 12.35 mm.

[0153] Next, the resistance value was measured while the sample 10' was pulled up at a predetermined speed. In this case, the speed at which the sample 10' was pulled up (test speed) was 8.3 mm / s, and the test stroke (distance pulled up) was 20 mm.

[0154] Afterward, the pair of contact members 91 and 92 were separated from each other to release the clamping state of the sample 10', and then the sample 10' was returned to its initial position.

[0155] The above process was repeated 10 times, and the average of the resistance values ​​measured at distances between 5 mm and 15 mm was calculated from the 10th measurement and defined as the sliding resistance value (gf). The results are shown in Table 1.

[0156]

[0157] As shown in Table 1, the surface lubrication layers of the dilators in Examples 1 to 3 exhibited superior sliding properties compared to the silicone coating of the dilator in Comparative Example 1. Furthermore, the superior sliding properties of the surface lubrication layers of the dilators in Examples 1 to 3 were maintained even after 10 measurements. In other words, the surface lubrication layers of the dilators in Examples 1 to 3 were shown to possess not only superior sliding properties but also superior durability.

[0158] [Evaluation of Operability] The operability was evaluated using samples 1 to 3 of Examples 1 to 3 and comparative sample 1 of Comparative Example 1, which were prepared as described above.

[0159] First, the operability was evaluated using the operability evaluation device 400 shown in Figures 5 and 6. The outline of the operability evaluation device 400 will be described below.

[0160] The operability evaluation device 400 comprises a blood vessel model 410, a container 420, a fixing plate 430, a fixing device 440, a light-emitting unit 450, and a marker unit 460. As shown in Figure 5, the evaluation device simulates at least a portion of the abdominal aorta V1, the common iliac artery V2, and the external iliac artery V3 as blood vessels simulated by the blood vessel model 410.

[0161] In the portion of the blood vessel model 410 corresponding to a blood vessel, a channel 411 is formed, which has a lumen 411a through which the liquid in the container 420 flows and through which the sheath assembly 30 and other components can be inserted and removed. The blood vessel model 410 is formed from a tube made of a flexible material such as silicone resin. The lumen 411a is coated with a low-friction material on its inner surface, which provides a slipperiness similar to that of an actual blood vessel.

[0162] The container 420 is a device for storing a liquid such as water and immersing and installing the blood vessel model 410. The container 420 can be a water tank made of a light-transmitting material (such as acrylic resin). A fixing plate 430 is placed on the upper or lower surface of the bottom 421 of the container 420.

[0163] The fixing plate 430 is a device on which the blood vessel model 410 is fixed by the fixing device 440. The fixing plate 430 can be made of a flat, transparent sheet that is translucent and through which light from the light-emitting unit 450 can pass.

[0164] The fixing device 440 is placed on the blood vessel model 410 and is a device for maintaining the shape and position of the blood vessel model 410. The fixing device 440 is mainly placed in the curved portion of the flow path 411 of the blood vessel model 410.

[0165] The placement of the fixing devices 440 relative to the vascular model 410 can be appropriately set based on the type of blood vessel simulated by the vascular model 410, the number of difficulty levels for training, etc. When determining the placement of the fixing devices 440, concentrating them in areas where fine adjustment of the curvature is particularly necessary makes it easier to deform the flow path 411 into the desired curved shape, allowing for adjustment to the appropriate amount of curvature.

[0166] The light-emitting unit 450 is composed of a lighting fixture or the like for irradiating (emitting light) light from the lower surface side of the fixed plate 430.

[0167] The marker portion 460 is used to adjust the curvature of the flow path 411 of the blood vessel model 410. The marker portion 460 can be formed on the fixing plate 430.

[0168] As shown in Figure 6, the marker unit 460 has a group of markers 462, which is a combination of multiple markers 461, in order to adjust the amount of curvature of the flow path 411 according to the difficulty of the procedure and the skill of the trainer, such as a doctor.

[0169] As shown in Figures 5 and 6, the markers 461 that make up the marker group 462 have a shape that matches the outer shape of the fixing device 440. In this embodiment, since the fixing device 440 is a circular suction cup, the markers 461 have an annular shape that follows the outer shape of the suction cup.

[0170] The marker group 462 is configured to allow adjustment of the curvature of the vascular model 410 according to the difficulty of the procedure and the skill level of the trainee by arbitrarily combining multiple markers 461. As shown in Figures 5 and 6, the marker group 462 can be combined with some overlapping markers 461 so that the difficulty of the training can be adjusted.

[0171] As shown in Figure 6, the marker section 460 divides the difficulty into three levels (1 to 3), with the first marker 461a positioned at the lowest difficulty level "1", the second marker 461b positioned at the medium difficulty level "2", and the third marker 461c positioned at the highest difficulty level "3". The difficulty level can be set such that the lower the difficulty, the less curvature the flow path 411 has and the gentler it becomes, and the higher the difficulty, the greater the curvature of the flow path 411 and the steeper it becomes. In this embodiment, as shown in Figure 6, the difficulty level of the marker section 460 is identified by the line type, with the first marker 461a represented by a solid line, the second marker 461b by a dotted line, and the third marker 461c by a dashed line.

[0172] Using the operability evaluation device 400 described above, the operability was evaluated according to the following procedure. The evaluation using the operability evaluation device 400 was performed for all three difficulty levels (1 to 3) described above. (1) First, a φ0.405 Ni-Ti wire was passed through the flow path 411 of the evaluation device described above, from one external iliac artery V3 side, over the common iliac artery V2, to the other external iliac artery V3 side (see Figure 7a). (2) Next, each dilator prepared above (samples 1 to 3 of Examples 1 to 3, and comparative sample 1 of Comparative Example 1) was inserted into the lumen of a catheter (guiding sheath (sheath)) (manufactured by Terumo Corporation, product name Destination, inner diameter 2.2 mm, outer diameter 2.8 mm) to form a sheath assembly. The sheath assembly was configured so that 20 mm from the tip of the dilator (i.e., the portion carrying the surface lubrication layer) protruded from the tip of the catheter body. (3) Next, the Ni-Ti wire that had already been threaded through the model of the operability evaluation device 400 was inserted into the dilator lumen (guidewire lumen) so that the sheath assembly could be inserted from the external iliac artery V3 side of the lumen of the operability evaluation device 400. (4) Next, each sheath assembly was inserted into the lumen of the operability evaluation device 400 on one side of the external iliac artery V3 along the Ni-Ti wire, and pushed past the bifurcation of the common iliac artery V2 toward the other side of the external iliac artery V3 (see Figure 7b). The operability (ease of passage) when crossing the ridge in this operation was evaluated by two operators based on the following criteria, and the results were used to evaluate operability. If the evaluation results were the same between the two operators, that result was adopted. On the other hand, if the evaluation results differed between the two operators, they each performed the evaluation again according to the above procedure, and then consulted with each other to decide on the evaluation result. The evaluation results are shown in Table 2.

[0173] (Evaluation Criteria) A: Passes through without resistance B: There is some resistance, but it can pass through with a light push C: There is strong resistance, but it can pass through with a strong push D: There is strong resistance and it cannot pass through.

[0174]

[0175] From the above results, it was found that the sheath assembly 30 using the samples of Examples 1 to 3 showed improved operability compared to the result using the sample of Comparative Example 1. From these results, it was found that the dilator 10 according to the present invention improves the operability of procedures using the sheath assembly 30. Furthermore, it was found that the sheath assembly 30 using the samples of Examples 2 and 3 showed even greater operability.

[0176] This application is based on Japanese Patent Application No. 2024-159018, filed on 13 September 2024, the disclosures of which are referenced and incorporated in whole.

[0177] 1: Base layer, 2: Surface lubrication layer, 3, 13: Guide wire lumen, 10: Dilator, 10': Sample, 11: Dilator body, 12: Dilator hub, 14: Tapered section, 20: Sheath, 21: Sheath tube, 22: Hub, 23: Common port, 24: Tube, 25: Three-way stopcock, 26: Lumen, 27: Tip opening, 30: Sheath assembly, 50: Test device, 91: Contact member, 92: Contact member, 400: Operability evaluation device, 410: Blood vessel model, 411: Flow path, 411a: Lumen, 420: Container, 421: Bottom, 430: Fixing plate, 440: Fixing device 450: Light-emitting unit, 460: Marker unit, 461: Marker, 461a: First marker, 461b: Second marker, 461c: Third marker, 462: Marker group, V1: Abdominal aorta, V2: Common iliac artery, V3: External iliac artery.

Claims

1. A dilator comprising a base layer and a surface lubricating layer supported on at least a portion of the base layer, wherein the base layer comprises a polyolefin resin and a contrast agent, and the surface lubricating layer comprises a block copolymer having constituent units (A) derived from a reactive monomer having an epoxy group and constituent units (B) derived from a hydrophilic monomer.

2. The dilator according to claim 1, wherein the surface lubricating layer further comprises at least one selected from the group consisting of polyvinyl chloride and silicone compounds.

3. The dilator according to claim 1, wherein the surface lubrication layer is supported on the base material layer at least at the tip of the dilator.

4. The dilator according to claim 1, wherein the contrast agent comprises at least one selected from the group consisting of bismuth compounds and barium compounds.

5. The dilator according to claim 1, wherein the polyolefin resin is a polypropylene resin.

6. The dilator according to claim 1, wherein the inner diameter of the tip is 2.0 mm or less.

7. The dilator according to claim 1, wherein the sliding resistance value of the surface lubrication layer is 1 gf or more and 30 gf or less.

8. A sheath assembly comprising a dilator according to any one of claims 1 to 7.

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