Elongated medical device, and method for producing elongated medical device

Abstract

To provide an elongated medical device that offers superior lubricity and ensures strong adhesion between a substrate and a coating layer, and a method for producing the same.SOLUTION: An elongated medical device 1 comprises a base material 11, a base layer 12, and a top layer 13, wherein the top layer 13 is formed from a polymer material in which a copolymer including a polymer unit with a hydrophilic structure is cross-linked with one of -CH(OH)-CH(R1)-O-C(=O)-NH-R2-NH-C(=O)-OCH(R1)-CH(OH)- (1), -CH(OH)-CH(R1)-O-C(=O)-NH-R2-NH-C(=O)-OCH(CH(R1)-OH)- (2), and -CH(CH(R1)-OH)-O-C(=O)-NH-R2-NH-C(=O)-OCH(CH(R1)-OH)- (3), the base layer 12 is formed from an isocyanate compound, and the isocyanate compound is bonded with the structures of formulas (1) to (3).SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to elongated medical devices and methods of making elongated medical devices. [Background technology]

[0002] Long medical devices such as guidewires, stents, and catheters that are inserted into the body are required to have lubricity relative to biological tissue in order to prevent damage to the biological tissues, such as blood vessels, with which they come into contact, and to improve the operability of the long medical device.

[0003] For this reason, a coating made of a hydrophilic polymer etc. is formed on the surface of such long medical devices. For example, Patent Document 1 discloses a medical device in which a surface lubricating layer is provided on the surface of a substrate, the surface lubricating layer being made of a hydrophilic polymer (a) having at least one reactive functional group selected from the group consisting of an epoxy group, an acid chloride group and an aldehyde group, and an antithrombotic material (b) having a functional group capable of bonding with the hydrophilic polymer (a). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 6495241 Summary of the Invention [Problem to be solved by the invention]

[0005] However, when a lubricating coating is provided on a substrate, as in the medical device disclosed in Patent Document 1, there is a problem in that the adhesion between the substrate and the coating is insufficient, and the coating is prone to destruction, falling off, loss, etc. during use.

[0006] The present invention has been made in consideration of the above-mentioned circumstances, and aims to provide a long medical device that exhibits excellent lubrication properties and excellent adhesion between the substrate and the coating, and a method for manufacturing the same. [Means for solving the problem]

[0007] In order to achieve the above object, first, the present invention provides a long medical device comprising a substrate, a base layer provided on the substrate, and a top layer provided on the base layer on the opposite side of the substrate, the top layer comprising a copolymer containing a polymerization unit having a hydrophilic structure represented by the following formulae (1) to (3): -CH(OH)-CH(R 1 )-OC(=O)-NH-R 2 -NH-C(=O)-OCH(R 1 )-CH(OH)- … (1) -CH(OH)-CH(R 1 )-OC(=O)-NH-R 2 -NH-C(=O)-OCH(CH(R 1 )-OH)- … (2) -CH(CH(R 1 )-OH)-OC(=O)-NH-R 2 -NH-C(=O)-OCH(CH(R 1 )-OH)- … (3) (In each formula, R 1 R may be the same or different and represent a hydrogen atom, a linear alkyl group having 1 or more carbon atoms, or a branched alkyl group having 1 or more carbon atoms. 2 represents an alkylene group having one or more carbon atoms, a divalent alicyclic hydrocarbon group containing an alicyclic structure having three or more carbon atoms, or a divalent aromatic group containing an aromatic ring structure having six or more carbon atoms, and the alkylene group, the alicyclic hydrocarbon group, and the aromatic group each have -NR 3 -(R 3may have a hydrogen atom or a divalent group represented by an alkyl group having 1 to 8 carbon atoms). The base layer is composed of an isocyanate compound having two or more isocyanate groups, and at least a part of the isocyanate groups in the isocyanate compound react with at least a part of the hydroxyl groups in the structures represented by the formulas (1) to (3) in the polymer material to form a covalent bond (Invention 1).

[0008] In the above invention (Invention 1), it is preferable that the base layer is formed from a base layer composition containing the isocyanate compound and a resin having at least one of a hydroxy group or a carboxy group (Invention 2).

[0009] In the above inventions (Inventions 1 and 2), the copolymer is preferably obtained by copolymerizing at least a polymerization unit having the hydrophilic structure and a polymerization unit having a cyclic carbonate structure (Invention 3).

[0010] In the above inventions (Inventions 1 to 3), the hydrophilic structure preferably contains at least one structure selected from the group consisting of a betaine structure, an amide structure, an alkylene oxide structure, and a lactam structure (Invention 4).

[0011] Secondly, the present invention provides a method for producing a long medical device, comprising: a base coating film forming step of applying a base layer composition containing an isocyanate compound having two or more isocyanate groups onto a substrate provided on the long medical device to form a base coating film; a top coating film forming step of applying a top layer composition containing a copolymer obtained by copolymerizing at least a polymerization unit having a hydrophilic structure and a polymerization unit having a cyclic carbonate structure, and a polyamine compound, onto the surface of the base coating film opposite the substrate to form a top coating film; and a heating step of heating the base coating film and the top coating film to form a base layer formed by hardening the base coating film and a top layer formed by hardening the top coating film (Invention 5). Effect of the Invention

[0012] The long medical device according to the present invention has a top layer on the surface of the substrate, and the top layer is made of a polymeric material containing a hydrophilic structure, thereby exhibiting excellent lubricity to biological tissue. In addition, a base layer is present between the substrate and the top layer, and the base layer is made of an isocyanate compound that forms a covalent bond with the polymeric material, so that the substrate and the top layer are sufficiently adhered to each other via the base layer, and the destruction, falling off, loss, etc. of the top layer are effectively suppressed. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a schematic cross-sectional view of a medical device according to one embodiment of the present invention. [Diagram 2] FIG. 2 is a diagram illustrating the formation of a crosslinked structure by the reaction of a copolymer with a polyamine compound. [Diagram 3] FIG. 13 is a diagram showing test results relating to adhesion. [Figure 4] FIG. 13 is a diagram showing test results relating to adhesion. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Hereinafter, an embodiment of the present invention will be described. FIG. 1 shows a schematic cross-sectional view of an elongated medical device according to one embodiment of the present invention. As shown in FIG. 1, the elongated medical device 1 of this embodiment comprises a substrate 11, a base layer 12 provided on the substrate 11, and a top layer 13 provided on the side of the base layer 12 opposite the substrate 11.

[0015] The top layer 13 is a copolymer containing a polymerization unit having a hydrophilic structure represented by the following formulas (1) to (3): -CH(OH)-CH(R 1 )-OC(=O)-NH-R 2 -NH-C(=O)-OCH(R 1 )-CH(OH)- … (1) -CH(OH)-CH(R 1 )-OC(=O)-NH-R 2 -NH-C(=O)-OCH(CH(R 1 )-OH)- … (2) -CH(CH(R 1 )-OH)-OC(=O)-NH-R 2 -NH-C(=O)-OCH(CH(R 1 )-OH)- … (3) (In each formula, R 1 R may be the same or different and represent a hydrogen atom, a linear alkyl group having 1 or more carbon atoms, or a branched alkyl group having 1 or more carbon atoms. 2 represents an alkylene group having 1 or more carbon atoms, a divalent alicyclic hydrocarbon group containing an alicyclic structure having 3 or more carbon atoms, or a divalent aromatic group containing an aromatic ring structure having 6 or more carbon atoms, and the alkylene group, the alicyclic hydrocarbon group, and the aromatic group each have -NR 3 -(R 3 may have a divalent group represented by a hydrogen atom or an alkyl group having 1 to 8 carbon atoms. The polymer is composed of a cross-linked polymer material having a structure represented by any one of the following:

[0016] The elongated medical device 1 according to this embodiment is provided with the top layer 13 made of a polymeric material containing the above-mentioned hydrophilic structure, and is therefore capable of exhibiting excellent lubricity to biological tissue.

[0017] The base layer 12 is composed of an isocyanate compound having two or more isocyanate groups. At least a part of the isocyanate groups in the isocyanate compound reacts with at least a part of the hydroxyl groups in the structures represented by the formulas (1) to (3) in the above-mentioned polymer material to form covalent bonds.

[0018] In the long medical device 1 of this embodiment, the substrate 11 and the top layer 13 are laminated via the base layer 12, thereby ensuring sufficient adhesion between the substrate 11 and the top layer 13, and through use of the long medical device 1 of this embodiment, damage, falling off, loss, etc. of the top layer 13 is effectively suppressed.

[0019] 1. Elements of long medical devices (1) Top Tier As described above, the top layer 13 in this embodiment is a copolymer containing a polymerization unit having a hydrophilic structure represented by the following formulas (1) to (3): -CH(OH)-CH(R 1 )-OC(=O)-NH-R 2 -NH-C(=O)-OCH(R 1 )-CH(OH)- … (1) -CH(OH)-CH(R 1 )-OC(=O)-NH-R 2 -NH-C(=O)-OCH(CH(R 1 )-OH)- … (2) -CH(CH(R 1 )-OH)-OC(=O)-NH-R 2 -NH-C(=O)-OCH(CH(R 1 )-OH)- … (3) The polymer is composed of a cross-linked polymer material having a structure represented by any one of the following:

[0020] In each formula, R1 may be the same or different and represent a hydrogen atom, a linear alkyl group having 1 or more carbon atoms, or a branched alkyl group having 1 or more carbon atoms. The upper limit of the number of carbon atoms in these alkyl groups is not particularly limited, but is preferably 4, for example.

[0021] On the other hand, R 2 is an alkylene group having one or more carbon atoms, a divalent alicyclic hydrocarbon group containing an alicyclic structure having three or more carbon atoms, or a divalent aromatic group containing an aromatic ring structure having six or more carbon atoms. In these, the alkylene group, the alicyclic hydrocarbon group, and the aromatic group have -NR 3 -(R 3 may have a divalent group represented by the formula (a hydrogen atom or an alkyl group having 1 to 8 carbon atoms). The upper limit of the number of carbon atoms in the alkylene group is not particularly limited, but is preferably, for example, 5. The upper limit of the number of carbon atoms in the alicyclic structure is not particularly limited, but is preferably, for example, 6. The number of carbon atoms in the alicyclic hydrocarbon group is not particularly limited, but is preferably, for example, 3 to 12. The upper limit of the number of carbon atoms in the aromatic ring structure is not particularly limited, but is preferably, for example, 10. The number of carbon atoms in the aromatic group is not particularly limited, but is preferably, for example, 6 to 20. The -NR 3 The number of divalent groups represented by - is not particularly limited, but is preferably 1 or 2, for example. 2 Among the above, alkylene groups having 1 to 6 carbon atoms are preferred, and alkylene groups having 4 to 6 carbon atoms are particularly preferred.

[0022] As described above, the copolymer contains a polymerized unit having a hydrophilic structure, but may contain other polymerized units. In particular, from the viewpoint of facilitating the formation of the crosslinked structures of the above formulae (1) to (3), it is preferable that the copolymer further contains a polymerized unit having a cyclic carbonate structure. The copolymer may also be crosslinked by a crosslinking agent to form the crosslinked structures of the above formulae (1) to (3). In this case, from the viewpoint of facilitating the formation of the crosslinked structures, it is preferable that the crosslinking agent is a polyamine compound. Hereinafter, the polymerized unit having a hydrophilic structure, the polymerized unit having a cyclic carbonate structure, and the polyamine compound will be described.

[0023] (1-1) Polymer unit having a hydrophilic structure The polymerized unit having a hydrophilic structure has a hydrophilic structure that imparts hydrophilicity to the polymerized unit. The hydrophilic structure is preferably a structure that is neutral in charge. Examples of the hydrophilic structure that is neutral in charge include a betaine structure, an amide structure, an alkylene oxide structure, and a lactam structure. However, the polymerized unit having a hydrophilic structure may be a polymerized unit having a hydrophilic structure other than the above-mentioned betaine structure, amide structure, alkylene oxide structure, and lactam structure, and it is also possible to use, for example, a polymerized unit having a charged hydrophilic structure that is not neutral in charge. The polymerized unit having a hydrophilic structure may be used alone or in combination of two or more different types.

[0024] The betaine structure refers to a structure that has a positive charge and a negative charge at non-adjacent positions in the same molecule, and the positively charged atom is not bound to dissociable hydrogen, and is neutral (has no charge) as a whole. In the betaine structure, the functional group having a positive charge can be, for example, any of quaternary ammonium, sulfonium, and phosphonium, and the functional group having a negative charge can be, for example, any of sulfonic acid, carboxylic acid, and phosphonic acid. That is, the betaine structure can be, for example, sulfobetaine, carboxybetaine, or phosphobetaine.

[0025] The betaine structure of this embodiment can have various combinations of the functional groups having positive charge and negative charge as described above.As the betaine structure of this embodiment, for example, structures derived from N-methacryloylaminopropyl-N,N-dimethylammonium-α-N-methylcarboxybetaine (MAMCMB), N-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine (CMB), 2-methacryloyloxyethyl-phosphorylcholine (MPC), 3-methacryloylaminopropyl-dimethyl-3-sulfobetaine (SMB) and the like can be suitably used.

[0026] In addition, when the copolymer according to the present embodiment contains a polymerization unit having a cyclic carbonate structure, it is preferable to open the cyclic carbonate structure of the polymerization unit and crosslink it with a polyamine compound as a crosslinking agent to harden it, as described below.At this time, when the functional group having a positive charge of the betaine structure has a quaternary ammonium, it is preferable because the quaternary ammonium can be a catalyst for the reaction related to the above-mentioned crosslinking.

[0027] The following formula (4) shows a polymer unit derived from N-methacryloylaminopropyl-N,N-dimethylammonium-α-N-methylcarboxybetaine (MAMCMB) as a polymer unit having a betaine structure as a hydrophilic structure. [ka]

[0028] The amide structure is a structure having an amide bond. Examples of polymerized units having an amide bond as a hydrophilic structure include polymerized units derived from N,N-dimethylacrylamide (DMAAm), N-isopropylacrylamide (NiPPAM), acrylamide (AAm), methylacrylamide (MAAm), 2-acrylamido-2-methylpropylsulfonic acid (AMPS), methacrylamide, N-vinylformamide, N-vinylacetamide, N-vinylpyrrolidone, etc. Among these, polymerized units derived from at least one of N,N-dimethylacrylamide (DMAAm), N-isopropylacrylamide (NiPPAM), acrylamide (AAm), methylacrylamide (MAAm), and 2-acrylamido-2-methylpropylsulfonic acid (AMPS) are preferred. The amide structures of these polymerized units are preferred in that they are not biased in charge and are neutral overall.

[0029] In addition, when the copolymer according to the present embodiment contains a polymerization unit having a cyclic carbonate structure, it is preferable to open the cyclic carbonate structure of the polymerization unit and crosslink it with a polyamine compound as a crosslinking agent to cure it, as described later. At this time, the tertiary ammonium of the amide structure is desirable because it can be a catalyst for the reaction related to the above-mentioned crosslinking.

[0030] The following formula (5) shows a polymer unit derived from N,N-dimethylacrylamide (DMAAm) as a polymer unit having an amide structure as a hydrophilic structure. [ka]

[0031] The alkylene oxide structure is a structure having an alkylene oxide group (-RO-; where R is an alkylene group, and the carbon number of R is preferably 1 to 5). Examples of polymerized units having a structure having an alkylene oxide group as a hydrophilic structure include polymerized units derived from alkoxy polyalkylene glycol acrylate, alkoxy polyalkylene glycol methacrylate, alkoxy alkyl acrylate, alkoxy alkyl methacrylate, etc.

[0032] More specific examples of polymerized units having a structure having an alkylene oxide group as a hydrophilic structure include polymerized units derived from methoxypolyethylene glycol acrylate, methoxypolyethylene glycol methacrylate, methoxyethyl acrylate, methoxyethyl methacrylate, methoxypolypropylene glycol acrylate, methoxypolypropylene glycol methacrylate, methoxymethyl acrylate, methoxymethyl methacrylate, ethoxymethyl acrylate, ethoxymethyl methacrylate, ethoxyethyl acrylate, ethoxyethyl methacrylate, ethoxypropyl acrylate, ethoxypropyl methacrylate, etc. The alkylene oxide structures of these polymerized units are preferred because they are free of charge bias and are neutral overall.

[0033] The following formula (6) shows a polymer unit derived from methoxypolyethylene glycol methacrylate (M90G) as a polymer unit having an alkylene oxide structure as a hydrophilic structure. [ka]

[0034] The following formula (7) shows a polymer unit derived from methoxyethyl acrylate (MEA) as a polymer unit having an alkylene oxide structure as a hydrophilic structure. [ka]

[0035] Examples of lactam structures include β-lactam (4-membered ring) structure, γ-lactam (5-membered ring) structure, δ-lactam (6-membered ring), structure, and ε-lactam (7-membered ring) structure, among which γ-lactam (5-membered ring) structure is particularly preferred. Examples of polymerization units having a lactam structure as a hydrophilic structure include vinyl monomers having a 5-membered ring lactam structure such as N-vinylpyrrolidone, N-vinyl-5-methylpyrrolidone, N-vinyl-5-ethylpyrrolidone, N-vinyl-5-propylpyrrolidone, N-vinyl-5-butylpyrrolidone, and 1-(2-propenyl)-2-pyrrolidone; vinyl monomers having a 6-membered ring lactam structure such as N-vinylpiperidone; and vinyl monomers having a 7-membered ring lactam structure such as N-vinylcaprolactam. The lactam structures of these polymerization units are preferred because they are not biased in charge and are neutral as a whole.

[0036] The following formula (8) shows a polymerization unit derived from N-vinylpyrrolidone (NVP) as a polymerization unit having a lactam structure as a hydrophilic structure. [ka]

[0037] As the polymerized unit having a hydrophilic structure, various hydrophilic polymerized units may be used in addition to the above-mentioned polymerized units. Examples of such polymerized units include polymerized units derived from acrylic acid, acrylic acid salts such as sodium acrylate, methacrylic acid, methacrylic acid salts such as sodium methacrylate, maleic anhydride, 2-hydroxyethyl methacrylate, (HEMA), 2-hydroxyethyl acrylate (2HEA), 2-hydroxypropyl acrylate (2HPA), 2-hydroxypropyl methyl acrylate (2HPMA), 4-hydroxybutyl acrylate (4HBA), 4-hydroxybutyl methacrylate (4HBMA), 1,4-cyclohexanedimethanol monoacrylate (CHDMA), lactic acid and other amino acids, acryloylmorpholine (AMP), N,N-dimethylaminoethyl acrylate, etc.

[0038] The content of the polymerized unit having a hydrophilic structure in the copolymer of this embodiment is preferably 50 mol% or more from the viewpoint of easily securing hydrophilicity, and more preferably 70 mol% or more, particularly preferably 80 mol% or more, and even more preferably 85 mol% or more from the viewpoint of easily obtaining superior lubricity. The content is also preferably 98 mol% or less, particularly preferably 97 mol% or less, and even more preferably 95 mol% or less. The content can also be adopted as the content of the polymerized unit having a betaine structure and the polymerized unit having an amide structure, which will be described later.

[0039] As the polymerization unit having hydrophilic structure, it is particularly preferable to use the polymerization unit having betaine structure.In this case, the content of the polymerization unit having betaine structure in the copolymer is preferably 10 mol% or more, more preferably 20 mol% or more, even more preferably 30 mol% or more, and even more preferably 40 mol% or more, from the viewpoint of easily obtaining better lubricity.In addition, even when using the polymerization unit having betaine structure as the polymerization unit having hydrophilic structure, it may be used in combination with the polymerization unit having at least one selected from amide structure, alkylene oxide structure and lactam structure.

[0040] As the polymerization unit having hydrophilic structure, it is also preferable to use the polymerization unit having amide structure.In this case, the content of the polymerization unit having amide structure in the copolymer may be 10 mol% or more, preferably 30 mol% or more, more preferably 50 mol% or more, even more preferably 70 mol% or more, even more preferably 80 mol% or more, and particularly preferably 85 mol% or more, from the viewpoint of obtaining better lubricity and increasing crosslinkability at low temperature.In addition, even when using the polymerization unit having amide structure as the polymerization unit having hydrophilic structure, it may be used in combination with the polymerization unit having at least one selected from betaine structure, alkylene oxide structure and lactam structure.

[0041] (1-2) Polymerization units having a cyclic carbonate structure The polymerization unit having a cyclic carbonate structure has at least one cyclic carbonate group of at least one kind. The polymerization unit having a cyclic carbonate structure of the present embodiment preferably has, for example, 1 to 3 cyclic carbonate groups, particularly preferably has 1 or 2 cyclic carbonate groups, and further preferably has 1 cyclic carbonate group.

[0042] An example of the above-mentioned "cyclic carbonate group" is shown in the following formula (9). [ka]

[0043] In the above formula (9), R 4 represents any one of a hydrogen atom, a linear alkyl group having 1 to 4 carbon atoms, a branched alkyl group having 1 to 4 carbon atoms, a linear alkenyl group having 1 to 4 carbon atoms, and a branched alkenyl group having 1 to 4 carbon atoms. 4 At least one hydrogen atom of R may be substituted with a halogen atom, and at least one carbon atom (-C-) of R may be substituted with -O-, -S-, or -P-. 4 In the above formula, examples of the linear or branched alkyl group having 1 to 4 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, etc. Examples of the linear or branched alkenyl group having 1 to 4 carbon atoms include groups in which at least one, preferably one, of the carbon-carbon direct bonds of the above alkyl groups is replaced with an unsaturated double bond. From the viewpoint of easily improving water resistance, R 4 is preferably a hydrogen atom or a methyl group, and more preferably a hydrogen atom.

[0044] In the above formula (9), R 5 represents a linear or branched alkylene or alkenylene group having 1 to 4 carbon atoms. 5At least one hydrogen atom of R may be substituted with a halogen atom, and at least one carbon atom (-C-) of R may be substituted with -O-, -S-, or -P-. 5 In the formula, examples of the linear or branched alkylene group having 1 to 4 carbon atoms include a methylene group, an ethylene group, an n-propylene group, an isopropylene group, an n-butylene group, a methylmethylene group, a methylethylene group, a dimethylethylene group, and a methylpropylene group. Examples of the linear or branched alkenylene group having 1 to 4 carbon atoms include the above alkylene groups in which at least one, preferably one, of the carbon-carbon direct bonds is replaced with an unsaturated double bond. From the viewpoint of easily improving water resistance, R 5 is preferably a linear or branched alkylene group having 1 to 4 carbon atoms, and more preferably a linear alkylene group having 1 carbon atom.

[0045] Specifically, the above-mentioned "cyclic carbonate group" is preferably a 2-oxo-1,3-dioxolane structure, and more specifically, is preferably a (2-oxo-1,3-dioxolan-4-yl) group.

[0046] The polymerized unit having a cyclic carbonate structure is preferably a polymerized unit derived from a (meth)acrylate having a cyclic carbonate group. In particular, the polymerized unit may be a polymerized unit derived from a (meth)acrylate having a cyclic carbonate group, such as a group represented by the following formula (10) and the R 5 and are preferably polymerized units derived from a (meth)acrylate in which the and are directly bonded to each other. CH2=CR 6 -R 7 -(CH2) n - … (10) (In the formula, R 6 represents a hydrogen atom or a methyl group, and R 7 represents -COO- or -CO-NH-, and n represents an integer of 1 to 4.

[0047] Specific examples of the above-mentioned (meth)acrylate having a cyclic carbonate group include (2-oxo-1,3-dioxolan-4-yl)methyl methacrylate (GCMA), (2-oxo-1,3-dioxolan-4-yl)methyl acrylate (GCA), and the like, with (2-oxo-1,3-dioxolan-4-yl)methyl methacrylate (GCMA) being particularly preferred.

[0048] The content of the polymerization units having a cyclic carbonate structure in the copolymer of this embodiment is preferably 2 mol % or more, more preferably 3 mol % or more, and even more preferably 5 mol % or more, from the viewpoint of ensuring adhesion between the top layer 13 and the base layer 12. Moreover, the content is preferably 50 mol % or less, more preferably 30 mol % or less, more preferably 20 mol % or less, and even more preferably 15 mol % or less.

[0049] (1-3) Other structures of the copolymer The copolymer in the present embodiment may contain structural units other than the above-mentioned polymer units having a hydrophilic structure and polymer units having a cyclic carbonate structure.

[0050] Examples of the other structural units include polymerization units having a long-chain aliphatic structure, such as polymerization units derived from n-butyl methacrylate and polymerization units derived from n-lauryl methacrylate. By containing these polymerization units, the glass transition temperature Tg of the copolymer is appropriately lowered, making it easier to soften the copolymer.

[0051] As another example of the other structural unit, a polymer unit having a functional group capable of forming a crosslink upon irradiation with light, such as a polymer unit derived from 4-methacryloyloxybenzophenone (MBP), 4-methacryloyloxy-2-hydroxybenzophenone (MHP), etc. may be used.

[0052] The copolymer in this embodiment may be a random copolymer of the above-mentioned polymerized units, or may be a block copolymer, or may be a mixture thereof.

[0053] The weight-average molecular weight of the copolymer in this embodiment is preferably 10,000 or more, and more preferably 40,000 or more. The weight-average molecular weight is preferably 1,000,000 or less, and more preferably 90,000 or less.

[0054] The method for producing the copolymer in the present embodiment is not particularly limited, and for example, a solution polymerization method, a bulk polymerization method, an emulsion polymerization method, a suspension polymerization method, etc. can be used. Among these, it is preferable to use a solution radical polymerization method.

[0055] (1-4) Polyamine compounds The polyamine compound is not particularly limited as long as it is a compound having two or more primary amines in the molecule. Examples of the polyamine compound include amine-based crosslinking agents such as aliphatic polyamines, alicyclic polyamines, and aromatic polyamines.

[0056] More specific examples of the aliphatic polyamine include hexamethylenediamine (HMDA), 1,4-butanediamine (BDA), diethylenetriamine (DETA), and triethylenetetramine (TETA).

[0057] More specific examples of the alicyclic polyamine include menthenediamine (MDA) and isophoronediamine (IPDA).

[0058] More specific examples of aromatic polyamines include meta-xylenediamine (m-XDA), diaminodiphenylmethane (DDM), m-phenylenediamine (m-PDA), etc. In particular, hexamethylenediamine (HMDA) is a long-chain aliphatic compound that has high structural reactivity and flexibility and is suitable as a crosslinking agent. It is also less toxic than other diamine compounds with shorter chain lengths, making it suitable for medical device applications.

[0059] The amount of polyamine compound added as a crosslinking agent is not particularly limited as long as it is capable of crosslinking with the cyclic carbonate structure to form the desired top layer 13, but is preferably 1 to 10 equivalents relative to 1 equivalent of the cyclic carbonate structure, more preferably 2 to 8 equivalents, and even more preferably 3 to 5 equivalents.

[0060] (1-5) Crosslinked structure Hereinafter, with reference to FIG. 2, a process in which the crosslinked structures of the above formulas (1) to (3) are formed by the reaction between the above copolymer and the polyamine compound will be described.

[0061] 2(a) is a schematic diagram of a copolymer having a polymerized unit having a hydrophilic structure and a polymerized unit having a cyclic carbonate structure. In the figure, the polymerized unit (α), the polymerized unit (β), and the polymerized unit (γ) are arranged in order, but this does not indicate the actual arrangement of the polymerized units in the copolymer, but means that the copolymer is composed of these three types of polymerized units arranged randomly.

[0062] In FIG. 2(a), the polymerized unit (α) and the polymerized unit (β) represent polymerized units having a hydrophilic structure, and the polymerized unit (γ) represents a polymerized unit having a cyclic carbonate structure. 8 represents a hydrogen atom (H) or a methyl group (CH3), and R 9 represents a group having a hydrophilic structure. As the polymerized unit (γ), a polymerized unit derived from (2-oxo-1,3-dioxolan-4-yl)methyl methacrylate (GCMA) is depicted.

[0063] Next, FIG. 2(b) shows hexamethylenediamine as a specific example of a polyamine compound.

[0064] FIG. 2(c) shows a structure (polyhydroxyurethane) formed by crosslinking the copolymer of FIG. 2(a) with the polyamine compound of FIG. 2(b). In FIG. 2(c), the portion other than the cyclic carbonate structure in the copolymer of FIG. 2(a) (the main chain of the copolymer) is simplified and shown with a wavy line. In the above crosslinking reaction, the amino group of the polyamine compound attacks the oxygen atom of the cyclic carbonate structure of the polymerization unit (γ), thereby opening the ring of the cyclic carbonate structure. At the same time, the carbon atom constituting the carbonyl group in the cyclic carbonate structure and the nitrogen atom constituting the amino group are covalently bonded to form a urethane bond (the portion surrounded by a two-dot chain line in FIG. 2(c)). The urethane bond is generated at each of the two amino groups of the polyamine compound, and a structure in which the copolymers are crosslinked with each other with the polyamine compound is formed.

[0065] With the opening of the cyclic carbonate structure, a hydroxyl group (the area surrounded by a dashed line in the figure) is also generated. The hydroxyl group reacts with the isocyanate group of the isocyanate compound constituting the base layer 12. As a result, the polymer material constituting the top layer 13 and the isocyanate compound constituting the base layer 12 are connected by a covalent bond, and the top layer 13 is firmly fixed to the base layer 12. Even if a hydroxyl group is present in the polymerization unit (α) or the polymerization unit (β), the hydroxyl group in the crosslinked structure (the area surrounded by a dashed line in the figure) is preferentially used for the covalent bond with the isocyanate compound, so that the consumption of the hydroxyl group in the polymerization unit (α) and the polymerization unit (β) is suppressed, thereby exhibiting high lubricity.

[0066] When the cyclic carbonate structure is opened, the crosslinked structure obtained may change depending on which oxygen atom is attacked by the amino group of the polyamine compound. That is, the cyclic carbonate structure of the copolymer shown in FIG. 2(a) has two oxygen atoms, but depending on the difference, two different structures are generated after the reaction. As a result of such differences occurring at both ends of the polyamine compound, three types of crosslinked structures shown in the above formulas (1) to (3) can be generated.

[0067] (1-6) Top layer composition Although the method for forming the top layer 13 in this embodiment is not particularly limited, from the viewpoint of facilitating the formation of the desired top layer 13, it is preferable to form the top layer 13 by previously preparing a composition for the top layer containing at least the above-mentioned copolymer and a polyamine compound, and applying the composition for the top layer to a predetermined position (the surface of the base layer 11 or a base layer coating film obtained by applying the composition for the base layer described later).

[0068] The above-mentioned top layer composition may further contain a solvent so that its concentration, viscosity, etc. are in an appropriate range. In particular, it is preferable to use a solvent so that the top layer composition can be easily applied. Examples of the solvent include alcohols such as ethanol, methanol, propanol, 2-propanol, butanol, and benzyl alcohol, and various hydrophilic polar solvents such as N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and dimethylacetamide (DMA). In addition, the top layer composition may contain a polymerization initiator or a catalyst as necessary.

[0069] The amount of the solvent may be appropriately adjusted to an amount that is easy to apply, and may be, for example, 10 to 99% by mass based on the total amount of the resulting coating solution of the top layer composition.

[0070] The coating film formed by applying the composition for the top layer can be heated to, for example, 70 to 150° C. to promote the above-mentioned crosslinking reaction and form the top layer 13. Note that, in addition to the heating for the crosslinking reaction, heating for volatilizing the solvent may be performed in advance. The heating for the crosslinking reaction may also serve as heating for inducing a reaction between the hydroxyl group of the polymer material constituting the top layer 13 and the isocyanate compound constituting the base layer 12.

[0071] (1-7) Thickness of top layer From the viewpoint of exhibiting good lubricity, the thickness of the top layer 13 is preferably 0.5 μm or more, particularly preferably 1.0 μm or more, and more preferably 2.0 μm or more. Moreover, from the viewpoint of suppressing excessive thickening of the coating and preventing the shape of the elongated medical device 1 from excessively deviating from the design range, the thickness of the top layer 13 is preferably 1000 μm or less, particularly preferably 100 μm or less, and more preferably 50 μm or less.

[0072] (2) Base layer As described above, the base layer 12 in this embodiment is composed of an isocyanate compound having two or more isocyanate groups. At least a part of the isocyanate groups in the isocyanate compound reacts with at least a part of the hydroxyl groups (hydroxyl groups surrounded by a dashed line in FIG. 2(c)) in the structures represented by the formulas (1) to (3) in the polymer material described above to form covalent bonds.

[0073] In addition, when a hydroxy group is present on the surface of the substrate 11, the hydroxy group may also react with the isocyanate group in the isocyanate compound to form a covalent bond. This improves the adhesion between the substrate 11 and the base layer 12, and further suppresses the destruction and falling off of the base layer 12 and the top layer 13 from the substrate 11. Even if a hydroxy group is not present on the surface of the substrate 11, the base layer 12 can be sufficiently adhered to the substrate 11 by mechanical bonding. That is, the base layer 12 is gripped by the microscopic or macroscopic unevenness on the surface of the substrate 11 to exhibit sufficient adhesion.

[0074] The base layer 12 may contain components other than the isocyanate compound, for example, a specific resin. In particular, the base layer 12 preferably contains a resin having at least one of a hydroxyl group and a carboxyl group together with the isocyanate compound. The hydroxyl group and the carboxyl group of the resin react with the isocyanate group in the isocyanate compound to form a covalent bond. As a result, it becomes easier to form a stronger base layer 12, and it becomes easier to suppress the destruction and falling off of the base layer 12 and the top layer 13 that accompanies the use of the long medical device 1.

[0075] (2-1) Isocyanate compounds The isocyanate compound is not particularly limited as long as it has two or more isocyanate groups. Specific examples thereof include aliphatic polyisocyanates such as hexamethylene diisocyanate, aromatic polyisocyanates such as tolylene diisocyanate, diphenylmethane diisocyanate, and xylylene diisocyanate, alicyclic polyisocyanates such as isophorone diisocyanate and hydrogenated diphenylmethane diisocyanate, and their biurets and isocyanurates, as well as adducts which are reaction products with low-molecular active hydrogen-containing compounds such as ethylene glycol, propylene glycol, neopentyl glycol, trimethylolpropane, and castor oil.

[0076] Among the above, it is preferable to use a biuret of hexamethylene diisocyanate, from the viewpoint that it reacts well with the hydroxyl groups of the polymeric material constituting the top layer 13, thereby easily achieving high adhesion.

[0077] (2-2) Resin having at least one of a hydroxy group and a carboxy group Examples of the resin having at least one of the above-mentioned hydroxy group and carboxy group are not particularly limited, but include (meth)acrylic resins, polyvinyl alcohol resins, polyhydroxyethyl methacrylate resins, polyethylene glycol resins, acrylic acid resins, maleic acid resins, etc. The (meth)acrylic resin may be any resin having polymerization units based on a monomer having an acryloyl group (HC=CH-C(=O)-) or a methacryloyl group (HC=C(CH)-C(=O)-).

[0078] When a resin having at least one of a hydroxyl group and a carboxyl group is used in combination with the isocyanate compound, the content of the resin is preferably 0.1 parts by mass or more, more preferably 0.4 parts by mass or more, and even more preferably 1.0 parts by mass or more, relative to 100 parts by mass of the isocyanate compound. The content of the resin is preferably 10,000 parts by mass or less, more preferably 5,000 parts by mass or less, and even more preferably 1,000 parts by mass or less, relative to 100 parts by mass of the isocyanate compound. By being within these ranges, the reaction between the isocyanate compound and the resin proceeds well, making it easier to form a stronger base layer 12.

[0079] (2-3)Other The base layer 12 may further contain other components in addition to the isocyanate compound and the resin having at least one of a hydroxyl group and a carboxyl group. For example, from the viewpoint of forming the base layer 12 more firmly and further improving the adhesion between the substrate 11 and the base layer 12 and between the base layer 12 and the top layer 13, vinyl chloride resins, urethane elastomers, nylon elastomers, polyether block amide elastomers, ethylene acrylic acid resins, epoxy resins, etc. may be used as the other components.

[0080] In addition, various catalysts for promoting the reaction of the isocyanate group may be added to the base layer 12. The catalyst is not particularly limited as long as it promotes the reaction between the isocyanate group and the hydroxyl group, and for example, an organotin catalyst, an organobismuth catalyst, various metal complex catalysts, an amine catalyst, etc. may be used. The catalyst may be added to either or both of the base layer 12 and the top layer 13, and the resin or polymer itself for forming the base layer 12 and the top layer 13 may be given a catalytic effect.

[0081] (2-4) Base layer composition Although the method of forming the base layer 12 in this embodiment is not particularly limited, from the viewpoint of facilitating the formation of the desired base layer 12, it is preferable to form the base layer 12 by previously preparing a base layer composition containing the above-mentioned isocyanate compound and a resin having at least one of a hydroxy group and a carboxy group, and applying the base layer composition to the surface of the substrate 11.

[0082] The base layer composition may further contain a solvent so that its concentration and viscosity are in an appropriate range. In particular, it is preferable to use a solvent so that the base layer composition can be easily applied. Specific examples of the solvent may be the same as the above-mentioned solvent for the top layer composition. The amount of the solvent in the base layer composition is also the same as that in the top layer composition. The base layer composition may also contain a polymerization initiator or a catalyst as necessary.

[0083] The coating film formed by applying the base layer composition can be heated to, for example, 50 to 150° C. to promote the reaction between the isocyanate group and the hydroxyl group, thereby forming the base layer 12. In addition to the heating for the reaction, heating for volatilizing the solvent may be performed in advance. The heating for the reaction may also serve as heating for causing the crosslinking reaction in the components constituting the top layer 13.

[0084] (2-5) Thickness of base layer The thickness of the base layer 12 is preferably 0.1 μm or more, more preferably 0.5 μm or more, and even more preferably 1.0 μm or more, from the viewpoint of sufficiently improving the adhesion between the top layer 13 and the substrate 11. Moreover, the thickness of the base layer 12 is preferably 1000 μm or less, more preferably 100 μm or less, and even more preferably 50 μm or less, from the viewpoint of suppressing excessive thickening of the coating and preventing the shape of the elongated medical device 1 from excessively deviating from the design range.

[0085] (3) Base material The structure and shape of the substrate 11 in this embodiment are appropriately selected depending on the type of the elongated medical device 1. The material constituting the substrate 11 is also appropriately selected depending on the type of the elongated medical device 1, and examples of the material include metal materials, polymeric materials, and ceramic materials, and a combination of multiple types of materials may be used.

[0086] The metallic material is not particularly limited as long as it is used for long medical devices, particularly long medical devices inserted or placed in a living body. For example, stainless steel such as SUS302, SUS304, and SUS316, nickel-titanium alloys, Carbon steel , nickel-chromium alloy, cobalt alloy, tungsten, etc. These may be used alone or in combination of two or more.

[0087] When the material constituting the substrate 11 is a metal material, the surface of the substrate 11 on which the base layer 12 is provided may be subjected to a treatment for enhancing adhesion of the base layer 12. Examples of such treatments include phosphoric acid treatment, ethylene-acrylic acid coating treatment, epoxy adhesive coating treatment, ozone / ultraviolet light treatment, plasma treatment, corona discharge treatment, flame treatment, radiation treatment, and the like.

[0088] The polymeric material is not particularly limited as long as it is used for long medical devices, particularly long medical devices to be inserted or placed in a living body, and examples thereof include polyamide, polyimide, modified polyolefin, polyvinyl alcohol, polyurethane, polyurea, polyester, polyether, polylactic acid, etc. These may be used alone or in combination of two or more.

[0089] Even when the material constituting the substrate 11 is a polymeric material, the surface of the substrate 11 on which the base layer 12 is provided may be subjected to a treatment for enhancing the adhesion of the base layer 12. Examples of such treatments include a primer treatment, an oxidation method, a roughening method, etc. Examples of the oxidation method include a corona discharge treatment, a chromic acid treatment, a flame treatment, a hot air treatment, an ozone / ultraviolet light treatment, a radiation treatment, etc., and examples of the roughening method include a sandblasting method, a solvent treatment method, etc.

[0090] (4) Long medical devices The type of long medical device 1 in this embodiment is not particularly limited as long as it requires lubricity for biological tissue, but it is generally preferable that the long medical device be one that is inserted or placed inside the living body, and a guidewire or catheter is particularly preferable.

[0091] Examples of the catheter are not particularly limited, and include, for example, a guiding catheter, a penetration catheter, a microcatheter, a balloon catheter, a foreign body removal catheter, a contrast catheter, a bile duct catheter, a urethral catheter, an endoscope, and a dilator.

[0092] Furthermore, examples of the guidewire are not particularly limited, and include, for example, a PCI guidewire for coronary artery treatment, a PTA guidewire for lower limb vascular treatment, an IVR guidewire for peripheral vascular treatment, an INR guidewire for cerebrovascular treatment, and a CAG guidewire for angiography.

[0093] As more specific configuration examples of the elongated medical device 1 of this embodiment, various configurations such as those shown in the following (a) to (e) can be adopted. (a) A guidewire comprising a linear core wire, a coating layer provided on at least a portion of the outer periphery of the core wire, and the above-mentioned base layer 12 and top layer 13 formed on the surface of the coating layer. (b) A guide wire comprising a linear core wire, a coil layer in which wire is wound spirally around at least a portion of the outer periphery of the core wire, and the above-mentioned base layer 12 and top layer 13 formed on the surface of the coil layer. (c) A guide wire comprising: a linear core wire; a coil layer in which wire is spirally wound around at least a portion of the outer periphery of the core wire; a coating layer provided on the outer periphery of the coil layer; and the above-mentioned base layer 12 and top layer 13 formed on the surface of the coating layer. (d) A catheter comprising a tubular member and the above-mentioned base layer 12 and top layer 13 formed on the surface of the tubular member. (e) A catheter comprising a tubular member, a balloon disposed at one end of the tubular member, and the above-mentioned base layer 12 and top layer 13 formed on the surface of the balloon.

[0094] However, the long medical device 1 of this embodiment may have a configuration different from those described above (a) to (e), and may be a long medical device other than a guidewire or a catheter, as long as at least a portion of the surface of the long medical device is provided with the above-mentioned base layer 12 and top layer 13.

[0095] 2. Manufacturing method for long medical devices The manufacturing method of the long medical device 1 according to this embodiment is not particularly limited as long as the long medical device 1 has the above-mentioned configuration. However, from the viewpoint of facilitating the formation of the above-mentioned configuration, it is preferable that the long medical device 1 according to this embodiment is manufactured by a manufacturing method including a base coating film forming step, a top coating film forming step, and a heating step, which will be described below.

[0096] (1) Base coating film formation process First, in the base coating film formation step, a base layer composition containing an isocyanate compound having two or more isocyanate groups is applied onto the substrate 11 provided on the long medical device 1 to form a base coating film.

[0097] As described above, the base layer composition may contain a solvent to facilitate application, and may also contain other components such as a resin having at least one of a hydroxyl group and a carboxyl group.

[0098] The method for applying the base layer composition is not particularly limited. For example, the base layer composition (coating solution) may be applied to the surface of the substrate 11 using a coater or the like, or the substrate 11 may be immersed in the base layer composition (coating solution) and pulled out at a constant speed.

[0099] After application of the base layer composition, a drying step may be optionally performed to volatilize the solvent and volatile components in the base coating film. The drying can be performed, for example, by heating at a temperature of 50° C. to 150° C. for 60 to 7200 seconds.

[0100] (2) Top coating process Next, in the top coating film formation process, a top layer composition containing a copolymer obtained by copolymerizing at least a polymerization unit having a hydrophilic structure and a polymerization unit having a cyclic carbonate structure, and a polyamine compound is applied to the surface of the base coating film formed as described above opposite the substrate 11 to form a top coating film.

[0101] As described above, the top layer composition may contain a solvent to facilitate application, and may contain other components in addition to the copolymer and polyamine compound.

[0102] The method for applying the top layer composition is not particularly limited. For example, the top layer composition (coating solution) may be applied to the surface of the base coating film using a coater or the like, or the substrate 11 after the base coating film is applied may be immersed in the top layer composition (coating solution) and pulled out at a constant speed.

[0103] After the application of the composition for the top layer, a drying step may be optionally performed to volatilize the solvent and volatile components in the top coating film. The drying can be performed, for example, by heating at a temperature of 50° C. to 150° C. for 60 to 7200 seconds.

[0104] (3)Heating process Finally, in the heating step, the base coating film and the top coating film formed as described above are heated to form a base layer formed by curing the base coating film and a top layer formed by curing the top coating film.

[0105] By the above heating, in the top coating film, the copolymer contained therein reacts with the polyamine compound, specifically, the cyclic carbonate group of the copolymer reacts with the polyamine compound to form a polymeric material in which the copolymers are crosslinked with each other through a hydroxyurethane structure (a structure containing a hydroxy group and a urethane structure), preferably a polymeric material having a structure represented by any one of the above formulas (1) to (3). Furthermore, at the interface between the top coating film and the base coating film, at least a part of the isocyanate group in the isocyanate compound contained in the base coating film reacts with at least a part of the hydroxyl group in the hydroxyurethane structure (preferably the structure represented by the above formulas (1) to (3)) in the polymeric material contained in the top coating film to form a covalent bond. This allows the long medical device 1 to be obtained, in which the substrate 11, the base layer 12, and the top layer 13 are laminated in this order.

[0106] In addition, when the base layer composition contains a resin having at least one of a hydroxy group and a carboxy group, the heating in the heating step also causes a reaction between the hydroxy group or carboxy group of the resin and the isocyanate group of the isocyanate compound. In addition, when a hydroxy group is present on the surface of the substrate 11, the heating in the heating step also causes a reaction between the hydroxy group and the isocyanate group of the isocyanate compound.

[0107] The heating temperature in the heating step is preferably 50°C or higher, more preferably 60°C or higher, and even more preferably 70°C or higher. This allows the various reactions described above to proceed efficiently. The temperature is also preferably 150°C or lower, more preferably 120°C or lower, and even more preferably 100°C or lower. This makes it easier to suppress thermal denaturation of the substrate 11 and the elongated medical device 1.

[0108] The heating time in the heating step is preferably 600 seconds or more, more preferably 1200 seconds or more, and even more preferably 1800 seconds or more. This allows the above-mentioned various reactions to proceed efficiently. The heating time is preferably 7200 seconds or less, more preferably 5400 seconds or less, and even more preferably 3600 seconds or less. This makes it easier to suppress thermal denaturation of the substrate 11 and the long medical device 1.

[0109] The above-described embodiments are described for the purpose of facilitating understanding of the present invention, and are not described for the purpose of limiting the present invention. Therefore, each element disclosed in the above embodiment is intended to include all design modifications and equivalents that fall within the technical scope of the present invention. EXAMPLES

[0110] The present invention will be described in more detail below with reference to examples, but the scope of the present invention is not limited to these examples.

[0111] Example 1 (1) Preparation of substrate The surface of a SUS304 metal wire with a diameter of 0.81 mm was coated with a thermoplastic polyamide elastomer (manufactured by ARKEMA, product name "PEBAX 35A NAT-R", polyether block amide copolymer) by hot melt extrusion molding. This resulted in a substrate in which the surface of the metal wire was covered with a thermoplastic polyamide elastomer coating of about 50 μm in thickness.

[0112] (2) Formation of the base layer An ethoxyethyl acetate solution containing an acrylic resin having 15 mol% of hydroxyl groups relative to the total polymerized units was prepared. 1.25 equivalents of polyisocyanate (trifunctional HDI nurate) per equivalent of hydroxyl groups of the acrylic resin was added to the solution as an isocyanate compound to obtain a coating solution for the base layer composition.

[0113] The substrate obtained in the above step (1) was immersed in the coating solution and pulled out at a constant speed to form a coating film of the base layer composition on the surface of the substrate. The coating film was then dried at 65°C for 15 minutes using a hot air circulation dryer to form a base layer.

[0114] (3) Formation of the top layer An acrylic copolymer was obtained by polymerizing 40 parts by mass of N-methacryloylaminopropyl-N,N-dimethylammonium-α-N-methylcarboxybetaine (MAMCMB), 50 parts by mass of methoxypolyethylene glycol methacrylate (M90G), and 10 parts by mass of (2-oxo-1,3-dioxolan-4-yl)methyl methacrylate (GCMA) by solution polymerization. Hereinafter, the copolymer may be referred to as "Poly(MAMCMB-M90G-GCMA) 40:50:10". The copolymer has a polymerization unit having a hydrophilic structure derived from MAMCMB and M90G, and a polymerization unit having a cyclic carbonate structure derived from GCMA.

[0115] The weight average molecular weight of the copolymer was measured to be about 100,000. Here, the weight average molecular weight and the weight average molecular weight of the copolymer described later are values ​​calculated as standard polystyrene measured by gel permeation chromatography (GPC).

[0116] The following formula (12) shows a schematic structure of the above-mentioned "Poly(MAMCMB-M90G-GCMA)40:50:10". Although "Poly(MAMCMB-M90G-GCMA)40:50:10" is a random copolymer, formula (12) shows the above-mentioned three structural units arranged in order. In formula (12), the cyclic carbonate structure is enclosed by a dashed line. [ka]

[0117] Next, an ethanol solution containing the copolymer prepared above at a concentration of 20% by mass was prepared, and then this solution was mixed with an ethanol solution containing 5% by mass of hexamethylenediamine (HMDA) as a crosslinking agent at a weight ratio of 5:3 to obtain a coating solution for a composition for a top layer.

[0118] Furthermore, the substrate having the base layer formed on the surface thereof obtained in the above step (2) was immersed in the coating solution of the composition for the top layer immediately after mixing, and was pulled out at a constant speed to form a coating film of the composition for the top layer on the surface of the base layer. The coating film was then heated at 100°C for 1 hour using a hot air circulation dryer. The heating caused the crosslinking reaction between the copolymer and the crosslinking agent in the coating film of the composition for the top layer to proceed, and also caused the reaction between at least a part of the hydroxyl groups in the crosslinked product formed thereby and at least a part of the isocyanate groups derived from the polyisocyanate in the base layer to proceed. As a result, a sample (a sample simulating a medical device) was obtained in which a base layer and a top layer were formed in that order on the surface of the substrate.

[0119] Example 2 An acrylic copolymer was obtained by polymerizing 90 parts by mass of N,N-dimethylacrylamide (DMAAm) and 10 parts by mass of (2-oxo-1,3-dioxolan-4-yl)methyl methacrylate (GCMA) by solution polymerization. Hereinafter, the copolymer may be referred to as "Poly(DMAAm-GCMA)90:10". The copolymer has a polymerization unit having a hydrophilic structure derived from DMAAm and a polymerization unit having a cyclic carbonate structure derived from GCMA. The weight-average molecular weight of the copolymer was measured to be about 90,000.

[0120] The following formula (13) shows a schematic structure of the above-mentioned "Poly(DMAAm-GCMA)90:10". Although "Poly(DMAAm-GCMA)90:10" is a random copolymer, formula (13) shows the above-mentioned two structural units arranged in order. In formula (13), the cyclic carbonate structure is enclosed by a dashed line. [ka]

[0121] A sample was obtained in which a base layer and a top layer were formed in that order on the surface of a substrate in the same manner as in Example 1, except that the above-mentioned "Poly(DMAAm-GCMA) 90:10" was used as the copolymer for forming the top layer, and the solvent for dissolving the copolymer was changed from ethanol to dimethylformamide.

[0122] Example 3 In preparing the substrate, a sample was obtained in the same manner as in Example 1, except that the thermoplastic polyamide elastomer was changed to a thermoplastic nylon elastomer (Polypla Evonik, product name "DIAMID L1940", polyamide elastomer). The sample had a base layer and a top layer formed in that order on the surface of the substrate.

[0123] Example 4 In preparing the substrate, a sample was obtained in the same manner as in Example 2, except that the thermoplastic polyamide elastomer was changed to a thermoplastic nylon elastomer (Polypla Evonik, product name "DIAMID L1940", polyamide elastomer). The sample had a base layer and a top layer formed in that order on the surface of the substrate.

[0124] Comparative Example 1 A sample was obtained in which a base layer and a top layer were formed in that order on the surface of a substrate in the same manner as in Example 1, except that no isocyanate compound was added when preparing the coating solution of the base layer composition.

[0125] Comparative Example 2 A sample was obtained in which a base layer and a top layer were formed in that order on the surface of a substrate in the same manner as in Example 2, except that no isocyanate compound was added when preparing the coating solution of the base layer composition.

[0126] Comparative Example 3 A sample was obtained in which a base layer and a top layer were formed in that order on the surface of a substrate in the same manner as in Example 3, except that no isocyanate compound was added when preparing the coating solution of the base layer composition.

[0127] Comparative Example 4 A sample was obtained in which a base layer and a top layer were formed in sequence on the surface of a substrate in the same manner as in Example 4, except that no isocyanate compound was added when preparing the coating solution of the base layer composition.

[0128] [Test Example 1] (Evaluation of lubricity) The samples according to Examples 1 to 4 and Comparative Examples 1 to 4 manufactured as described above were immersed in physiological saline. Then, for each sample taken out of the physiological saline, the portion where the top layer and the base layer were provided was pinched between the fingertips and rubbed once, and the tactile evaluation was performed based on the following criteria. The results are shown in Table 1 as an evaluation of "initial lubricity". A: A good slippery feeling was observed. B: The slipperiness was insufficient.

[0129] After the above tactile evaluation, the sample was rubbed 10 times in the same manner as above, and then the tactile evaluation was performed again. The results are shown in Table 1 as an evaluation of "lubricity after rubbing."

[0130] Furthermore, the impressions of lubricity in the series of evaluations described above for each sample are shown in the "Surface Condition" column of Table 1. Table 1 also shows the coating of the substrate for each sample, the presence or absence of an isocyanate compound in the base layer, and the type of copolymer in the top layer.

[0131] [Table 1]

[0132] As is clear from Table 1, the samples according to the examples exhibited good lubricity. Furthermore, the samples according to the examples were able to exhibit good lubricity even after 10 times of rubbing. From this, it is presumed that the base layer contains an isocyanate compound, which allows the base layer and the top layer to adhere well to each other, and as a result, the lubricity can be maintained well.

[0133] Example 5 A sample was obtained in which a base layer and a top layer were formed in sequence on the surface of a substrate in the same manner as in Example 1, except that a SUS304 plate was used as the substrate and a base layer and a top layer were formed in sequence on one side of the substrate using a bar coater.

[0134] Comparative Example 5 A sample was obtained in which a base layer and a top layer were formed in that order on the surface of a substrate in the same manner as in Example 5, except that no isocyanate compound was added when preparing the coating solution of the base layer composition.

[0135] [Test Example 2] (Evaluation of Adhesion) A cross-cut test (JIS K5600-5-6:1999) was performed on the surfaces of the samples according to Example 5 and Comparative Example 5 on which the base layer and top layer were formed, to evaluate the adhesion of the base layer and top layer to the substrate.

[0136] Specifically, a cutter knife was used to make grid-like cuts at 1 mm intervals on the base layer and top layer, transparent adhesive tape was attached and then peeled off, and the state of the grid was observed to confirm the state of peeling of the coating. The detailed test conditions were in accordance with JIS K5600-5-6:1999.

[0137] The test results are shown in Figures 3 and 4. Figure 3 is an image of the notched portion of the sample according to Example 5. Figure 4 is an image of the notched portion of the sample according to Comparative Example 5.

[0138] As is clear from FIG. 3, in the sample according to Example 5 (the sample in which an isocyanate compound is used in the formation of the base layer), no peeling occurred in the base layer and the top layer in any of the lattices (evaluation result defined in the JIS standard: Class 0).

[0139] On the other hand, as is clear from Fig. 4, in the sample according to Comparative Example 5 (a sample in which an isocyanate compound is not used in forming the base layer), peeling of the base layer and the top layer occurred in many areas where the test was performed (evaluation result defined in the JIS standard: Class 4). In particular, in this sample, in addition to peeling at the interface between the substrate and the base layer, peeling was also confirmed to have occurred at the interface between the base layer and the top layer.

[0140] From the above results, it was found that the use of an isocyanate compound in the formation of the base layer improves the adhesion at the interface between the substrate and the base layer, as well as the adhesion at the interface between the base layer and the top layer. This improvement in adhesion is presumably due to the reaction between the isocyanate group in the isocyanate compound in the base layer and the hydroxyl group in the polymer material in the top layer, resulting in a covalent bond between them. [Industrial Applicability]

[0141] The elongated medical device according to the present invention is suitable as, for example, a guidewire, a catheter, and the like. [Explanation of symbols]

[0142] 1. Long medical devices 11...Base material 12...Base layer 13…Top tier

Claims

1. A base material, A base layer provided on the base material, A top layer provided on the side of the base layer opposite to the base material, A long medical device comprising: The top layer is composed of a polymer material in which a copolymer containing a polymerization unit having a hydrophilic structure is crosslinked by a structure represented by any of the following formulas (1) to (3): -CH(OH)-CH(R １ )-O-C(=O)-NH-R ２ -NH-C(=O)-OCH(R １ )-CH(OH)-… (1) -CH(OH)-CH(R １ )-O-C(=O)-NH-R ２ -NH-C(=O)-OCH(CH(R １ )-OH)-…(2) -CH(CH(R １ )-OH)-O-C(=O)-NH-R ２ -NH-C(=O)-OCH(CH(R １ )-OH)-…(3) (In each formula, R １ may be the same or different and represents a hydrogen atom, a linear alkyl group having 1 or more carbon atoms, or a branched alkyl group having 1 or more carbon atoms. R ２ is an alkylene group having 1 or more carbon atoms, a divalent alicyclic hydrocarbon group containing an alicyclic structure having 3 or more carbon atoms, or a divalent aromatic group containing an aromatic ring structure having 6 or more carbon atoms, and the alkylene group, the alicyclic hydrocarbon group, and the aromatic group have a divalent group represented by -NR ３ -(R ３ is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms) may be included.) The base layer is composed of an isocyanate compound having two or more isocyanate groups, At least a part of the isocyanate groups in the isocyanate compound reacts with at least a part of the hydroxy groups in the structure represented by the formulas (1) to (3) in the polymer material to form a covalent bond. A long medical device characterized by the above.

2. The long medical device according to claim 1, wherein the base layer is formed of a base layer composition containing the isocyanate compound and a resin having at least one of a hydroxy group and a carboxy group.

3. The long medical device according to claim 1 or 2, wherein the copolymer is obtained by copolymerizing at least a polymerization unit having a hydrophilic structure and a polymerization unit having a cyclic carbonate structure.

4. The long medical device according to claim 1 or 2, wherein the hydrophilic structure includes at least one structure selected from the group consisting of a betaine structure, an amide structure, an alkylene oxide structure, and a lactam structure.

5. A method for manufacturing a long medical device, comprising: A base coating film forming step of applying a base layer composition containing an isocyanate compound having two or more isocyanate groups onto a base material provided in the long medical device to form a base coating film; A top coating film forming step of applying a top layer composition containing a copolymer obtained by copolymerizing at least a polymerization unit having a hydrophilic structure and a polymerization unit having a cyclic carbonate structure and a polyamine compound onto the surface of the base coating film opposite to the base material to form a top coating film; A heating step of heating the base coating film and the top coating film to form a base layer formed by curing the base coating film and a top layer formed by curing the top coating film. A method for manufacturing a long medical device, characterized by the above.

6. The method for manufacturing a long medical device according to claim 5, wherein the polyamine compound is a compound represented by the following formula (4).

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