JP2011177381A - Medical instrument system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medical instrument system showing superior operability. <P>SOLUTION: A medical instrument system includes a first hollow medical instrument and a second medical instrument into which the first medical instrument is inserted. A first surface lubrication layer including a first hydrophilic macromolecule with an electric charge is coated on at least a part of an inner surface of the first medical instrument. A second surface lubrication layer including a second hydrophilic macromolecule which has the electric charge of the same sign as that of the first hydrophilic macromolecular is coated on at least a part of an outer surface of the second medical instrument. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a medical device system, and more particularly to a medical device system for intravascular diagnosis or treatment. More specifically, the present invention relates to a medical device system excellent in operability and lubricity, and more particularly to a medical device system for intravascular diagnosis or treatment.

  A medical device inserted into a living body such as a catheter or a guide wire is required to exhibit excellent lubricity in order to reduce tissue damage such as blood vessels and improve operability for an operator. For this reason, guide wires and catheters in which a hydrophilic polymer having lubricity is coated on the surface of a substrate have been developed and put into practical use.

  Here, considering the case where the catheter is operated along the guide wire, the outer surface of the catheter mainly contacts the blood vessel wall, and the inner surface of the catheter contacts the guide wire. The friction generated between the catheter and the guide wire is not negligible when operating the catheter, and in some cases, it directly affects the operability rather than the friction between the catheter and the vessel wall. That is, it is desirable that the catheter has low frictional properties not only on the outer surface but also on the inner surface. In order to satisfy these requirements, a catheter with a highly slippery PTFE coated on the inner surface (for example, Patent Document 1) or a catheter with a hydrophilic lubrication coat on the inner surface (for example, Patent Documents 2 and 3). Has been devised. However, there is still a need for a technology that further improves operability. In recent years, it has also been reported that a polymer brush having an electrolyte polymer chain grafted on a solid surface can reduce friction in an aqueous solvent (Non-Patent Document 1), but is fixed to the surface of a substrate only by hydrophobic interaction. However, the polymer graft chain has a problem that its durability is not sufficient and a sufficient effect cannot be exhibited when the unevenness of the base material is large, and it has not been put into practical use.

  Moreover, the coating of the medical device inserted into the living body is required to have not only excellent lubricity but also high biocompatibility. In particular, in the case of a medical device inserted into a blood vessel, the formation of a thrombus on the surface of the medical device is problematic in terms of both operability and safety. For this reason, it is desirable that the medical device surface has antithrombogenicity. As a method for imparting antithrombogenicity to a medical device, a method of coating the surface of the medical device with a water-soluble polymer has been devised (for example, Patent Document 4), and it is known that adsorption of platelets and plasma proteins can be suppressed. ing. However, although the surface of the material coated with a water-soluble polymer suppresses the adsorption of plasma proteins, etc., platelets and microthrombi activated on the material surface are returned to the body, and abnormal fluctuations in blood cell components are observed. It was sometimes a problem. From such a viewpoint, for the purpose of more actively suppressing blood coagulation, a technique for coating a surface of a medical device with a substance that inhibits blood coagulation such as heparin has been devised (for example, Patent Documents 5 and 6). ).

Japanese Patent Laid-Open No. 2001-190681 JP 2001-129074 A Special table 2003-510134 gazette JP 2008-220786A JP-A-8-24327 JP-A-9-131396

NATURE Vol. 425 pp. 163-165 (2003)

  However, a technique for sufficiently satisfying both lubricity and antithrombogenicity has not been put into practical use, and even with the medical device described in Patent Documents 5 and 6, the lubricity and antithrombogenicity are further improved. Is desired.

  Accordingly, an object of the present invention is to solve the above-mentioned problems of the prior art and to provide a medical device system that exhibits superior operability in the blood vessel that has not been heretofore, particularly a medical device system for endovascular treatment. is there.

  Another object of the present invention is to provide a medical device system, particularly a medical device system for endovascular treatment, which can suppress a decrease in operability due to thrombus formation and maintain good operability for a long time.

  As a result of intensive studies to solve the above problems, the present inventors have obtained a medical device system in which another medical device is inserted into a hollow medical device such as a combination of a catheter and a guide wire. However, we focused on the friction between the two, not the lubricious coating technology for catheters and guidewires alone. As a result, by using the electrostatic repulsive force acting on the inner surface of the catheter and the outer surface of the guide wire, or the inner surface of the parent catheter and the outer surface of the child catheter that passes through the inner surface, the friction generated between them is reduced. It was learned that can be achieved. Based on the above findings, the present invention has been completed.

  That is, the object is a medical device system having a hollow first medical device and a second medical device inserted into the first medical device, and at least a part of the first medical device. A first surface lubricating layer containing a first hydrophilic polymer having a charge is coated on the inner surface of the first medical device, and the first hydrophilic property is formed on at least a part of the outer surface of the second medical device. This is achieved by a medical device system in which a second surface lubricating layer containing a second hydrophilic polymer having a charge of the same sign as that of the polymer is coated.

  According to the present invention, excellent operability can be achieved.

It is sectional drawing which shows the outline | summary of the medical device system of this invention. It is a figure of the apparatus used by the slidability evaluation test in Example 1 and Comparative Examples 1-3. It is a figure which shows the slidability evaluation result in Example 1 and Comparative Examples 1-3. It is a figure which shows the antithrombogenicity evaluation result of the copolymer of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and acrylic acid (AAc) in Reference Example 1.

  The present invention is also referred to as a hollow first medical device (hereinafter also referred to as “medical device 2”) and a second medical device (hereinafter referred to as “medical device 1”) inserted into the first medical device. ), A first hydrophilic polymer having a charge on the inner surface of at least a part of the first medical device (hereinafter also referred to as “hydrophilic polymer (B)”). A first surface lubricating layer (hereinafter also referred to as “surface lubricating layer (B)”) is coated, and the first hydrophilic high surface layer is formed on at least a part of the outer surface of the second medical device. A second surface lubricating layer (hereinafter referred to as “surface lubricating layer (A)”) containing a second hydrophilic polymer (hereinafter also referred to as “hydrophilic polymer (A)”) having the same sign as the charge of the molecule A medical device system is provided. The present invention is characterized in that the charge on the outer surface of the medical device 1 and the charge on the inner surface of the medical device 2 are assigned the same number. Thus, the medical device 2 and the medical device 1 are coated on the inner surface of the medical device 2 such as a catheter and the outer surface of the medical device 1 such as a guide wire with a hydrophilic polymer having the same sign. An electrostatic repulsive force is exerted between the two (for example, between the catheter and the guide wire), and friction can be reduced by the repulsive force. Therefore, according to the medical device system of the present invention, for example, in the case of the catheter and the guide wire, excellent operability can be exhibited such that the guide wire can be smoothly passed through the catheter. For this reason, the burden on the surgeon is reduced, and also in the patient, the operation time is shortened and the burden on the patient can be reduced. Further, when the hydrophilic polymer (A) or (B) has a sulfo group, the hydrophilic polymer exhibits antithrombotic properties. For this reason, by using such a medical device system, it is possible to further suppress deterioration in operability due to thrombus formation and to maintain good operability for a long time.

  Embodiments of the present invention will be described below.

[Medical device system]
FIG. 1 is a cross-sectional view showing an outline of the medical device system of the present invention. In addition, in FIG. 1, although the case where hydrophilic polymer (A) and (B) has a negative charge is described, this invention is not limited to the said form, hydrophilic polymer (A) and ( The form in which B) has a positive charge is defined similarly. In the present specification, unless otherwise specified, the medical device 1 and the medical device 2 are collectively referred to as “medical device” and the hydrophilic polymers (A) and (B) having a charge are collectively referred to as “highly hydrophilic. The “molecule” and the surface lubrication layers (A) and (B) are collectively referred to as “surface lubrication layer”, respectively.

  As shown in FIG. 1, the medical device system of the present invention has a medical device 1 and a hollow medical device 2 into which the medical device 1 is inserted. Here, at least a part of the outer surface of the medical device 1 is covered with a surface lubricating layer (A) containing a hydrophilic polymer (A) having a charge. Further, at least a part of the inner surface of the medical device 2 is covered with a surface lubricating layer (B) containing a hydrophilic polymer (B) having a charge. At this time, the charge of the hydrophilic polymer (A) constituting the surface lubricating layer (A) and the charge of the hydrophilic polymer (B) constituting the surface lubricating layer (B) are the same numbers. . With such a configuration, the charges of the same number (negative charge in FIG. 1) face each other, and the outer surface of the medical device 1 (surface lubrication layer (A)) and the inner surface of the medical device 2 (surface lubrication layer) (B)) generates an electrostatic repulsive force, and this repulsive force reduces the friction generated between the outer surface of the medical device 1 and the inner surface of the medical device 2. Therefore, the medical device system of the present invention is, for example, a combination of a catheter (medical device 2) and a guide wire (medical device 1) (medical device system) when the cross-sectional area of the catheter lumen into which the guide wire is inserted is small. Even so, the surgeon can smoothly pass the guide wire through the catheter lumen. For this reason, the burden on the surgeon is reduced, and also in the patient, the operation time is shortened and the burden on the patient can be reduced. In addition to the above, since the friction generated between the guide wire and the catheter lumen is small, peeling of the coating on the catheter inner surface and the guide wire outer surface can be suppressed / prevented. Therefore, good operability can be maintained for a long time. In addition, when the hydrophilic polymer has a sulfo group, the hydrophilic polymer exhibits antithrombotic properties, and further exhibits superior operability such as the ability to suppress / prevent deterioration of operability due to thrombus formation. it can.

  Therefore, the medical device system of the present invention is not particularly limited as long as it has a structure having the medical device 1 and the hollow medical device 2 into which the medical device 1 is inserted. Specific medical device combinations of the medical device system of the present invention include a guide wire (medical device 1) and a guiding catheter (medical device 2), a guide wire (medical device 1) and a balloon catheter (medical device 2), Examples thereof include a medical device system comprising a combination of a guide wire (medical device 1) and a contrast catheter (medical device 2), a balloon catheter (medical device 1) and a guiding catheter (medical device 2).

  The material of the medical device (base material) on which the surface lubricating layer is formed is not particularly limited, and is appropriately selected from materials usually used in the medical devices 1 and 2, and is made of metal, polymer, ceramic, or a composite material thereof. Either may be sufficient. Among these, as a metal, it does not restrict | limit in particular, A well-known medical metal can be used. Specifically, iron, titanium, aluminum, tin, gold, silver, copper, platinum, and alloys thereof, stainless steel such as SUS304, SUS316L, SUS420J2, and SUS630, nickel-titanium alloy (Ni-Ti alloy), cobalt- Examples of the alloy include a chromium alloy and a zinc-tungsten alloy. The polymer is not particularly limited, and a known medical polymer can be used. Specific examples include polyolefins, modified polyolefins, polyethers, polyurethanes, polyamides, polyimides, polyesters and copolymers thereof. In addition, the base material may be molded by a single polymer, or the polymer may be present on the surface of the base material. The ceramic is not particularly limited, and a known medical ceramic can be used. Specifically, silicon (Si), titanium (Ti), tantalum (Ta), tungsten (W), zirconium (Zr), niobium (Nb), chromium (Cr), aluminum (Al) oxide, carbide, Examples thereof include nitrides and nitrocarbides, bioactive ceramics such as apatite and biological glass. The shape of the substrate is not particularly limited, and is appropriately determined depending on the type of medical device to be used.

[Surface lubrication layer]
In the present invention, the surface lubricating layers (A) and (B) contain the hydrophilic polymers (A) and (B) having the charge of the same number, so that the charge of the same number is opposed to the medical device. An electrostatic repulsive force is generated between the outer surface (surface lubrication layer (A)) of 1 and the inner surface (surface lubrication layer (B)) of the medical device 2, and this repulsive force is the outer surface of the medical device 1. And the inner surface of the medical device 2 are reduced. Therefore, the surface lubrication layer is not particularly limited as long as it has the above-described configuration, and may have any characteristics, but the surface lubrication layer itself exhibits good lubricity and is peeled off. Or it is desirable that it is firmly fixed to the medical device as a base material without eluting.

  On the other hand, in a conventional medical device, a hydrophilic polymer having a charge forming a surface lubricating layer (hereinafter also simply referred to as “hydrophilic polymer”) is poor in lubricity even when coated on the surface alone. Or may be easily eluted or brittle. For this reason, from the viewpoint of solving such a problem, the surface lubricating layer preferably further includes a hydrophilic lubricating coating agent having a reactive functional group (hereinafter, also simply referred to as “hydrophilic lubricating coating agent”). . In this way, the hydrophilic lubricating coating agent and the charged hydrophilic polymer are mixed and coated on the base material to form a surface lubricating layer, whereby the hydrophilic lubricating coating agent and the charged hydrophilic polymer are formed. To give a cross-linked structure to the surface lubricating layer. Thereby, it is possible to suppress / prevent the release of the hydrophilic polymer from the surface lubricating layer or the base material. Therefore, the surface lubricant layer (hydrophilic polymer) can be easily and firmly fixed on the surface of the medical device (base material) by using the hydrophilic lubricant coating agent that exhibits good lubricity as in the above-mentioned form. Is possible.

  In the present invention, the surface lubricating layer (A) containing the hydrophilic polymer (A) only needs to cover at least a part of the outer surface of the medical device 1, and the hydrophilic polymer (B). The surface lubrication layer (B) containing suffices to cover at least a part of the inner surface of the medical device 2. Here, the covering portion is not particularly limited as long as it is at least a part of the outer surface of the medical device 1 and the inner surface of the medical device 2, but the portion where the outer surface of the medical device 1 and the inner surface of the medical device 2 are in contact with each other. Is preferably coated with a surface lubricating layer. In such a form, an electrostatic repulsive force is generated at the contact portion between the outer surface of the medical device 1 and the inner surface of the medical device 2, and the outer surface of the medical device 1 and the inner surface of the medical device 2 are in contact with each other. Since the friction can be reduced, the operator can easily operate the medical device system of the present invention.

  Further, the thickness of the surface lubricating layer according to the present invention is not particularly limited, but in consideration of operability, lubricity, etc., the thickness of the surface lubricating layer (when wet) is preferably 0.1 to 50 μm, More preferably, it is 0.5-20 micrometers.

[Hydrophilic polymer with charge]
In the present invention, a hydrophilic polymer having a charge is formed on at least a part of the outer surface of the medical device 1 and at least a part of the inner surface of the medical device 2 to form a surface lubricating layer. The hydrophilic polymer having electric charge is not particularly limited as long as the surface of the lubricating layer is positively or negatively charged, and may have any characteristic. That is, the hydrophilic polymer according to the present invention includes either a structural unit derived from a monomer having a positively charged functional group or a structural unit derived from a monomer having a negatively charged functional group. May be.

Here, the monomer having a positively charged functional group is not limited to the following, but includes an amino group (—NH ₂ ), an imino group (═NH, —NH—), an imidazolyl group, and a pyridyl group. And monomers having at least one functional group selected from a group and the like.

  Among the above, the monomer having an amino group is not particularly limited. For example, (meth) allylamine, aminoethyl (meth) acrylate, aminopropyl (meth) acrylate, dimethylaminoethyl (meth) acrylate, diethylaminoethyl Examples include (meth) acrylate, methylethylaminoethyl (meth) acrylate, dimethylaminopropyl (meth) acrylate, dimethylaminostyrene, diethylaminostyrene, morpholinoethyl (meth) acrylate, and lysine.

  The monomer having an imino group is not particularly limited. For example, N-methylaminoethyl (meth) acrylate, N-ethylaminoethyl (meth) acrylate, Nt-butylaminoethyl (meth) acrylate, ethylene Examples include imines.

  The monomer having an imidazolyl group is not particularly limited, and examples thereof include 4-vinylimidazole, N-vinyl-2-ethylimidazole, N-vinyl-2-methylimidazole, and the like.

  Although it does not restrict | limit especially as a monomer which has a pyridyl group, For example, 2-vinylpyridine, 4-vinylpyridine, 2-methyl-5-vinylpyridine etc. are mentioned.

The monomer having a negatively charged functional group is not limited to the following, but is a sulfo group (—SO ₃ H), a carboxyl group (—COOH), a phosphonic acid group (—PO ₃ H). ₂ ) and other monomers having at least one functional group.

Among the above, the monomer having a sulfo group (—SO ₃ H) is not particularly limited, and examples thereof include vinyl sulfonic acid (ethylene sulfonic acid), 2-propene sulfonic acid, 3-butene sulfonic acid, 4- Pentenesulfonic acid, sulfomethyl (meth) acrylate, 2-sulfoethyl (meth) acrylate, 3-sulfopropyl (meth) acrylate, 2-methyl-3-sulfopropyl (meth) acrylate, (meth) acrylic acid 4 -Sulfobutyl, N- (2-sulfoethyl) (meth) acrylic acid 4-sulfobutyl, 2- (meth) acrylamide-2-methylpropanesulfonic acid, N- (2-sulfoethyl) (meth) acrylamide, N- (1- Methyl-2-sulfoethyl) (meth) acrylamide, N- (2-methyl-3-sulfopropyl) (meth) acryl Amide, N- (4-sulfobutyl) (meth) acrylamide, 10-sulfodecyl (meth) acrylate, styrene sulfonic acid, (meth) allyl sulfonate, allyl sulfonic acid, 3- (meth) acryloxy-2-hydroxypropyl sulfonate, 3 -(Meth) acryloxy-2-hydroxypropylsulfophenyl ether, 3- (meth) acryloxy-2-hydroxypropyloxysulfobenzoate, 4- (meth) acryloxybutylsulfonate, (meth) acrylamidomethylsulfonic acid, (meth) Examples include acrylamidoethylsulfonic acid and 2-methylpropanesulfonic acid (meth) acrylamide.

  In addition, the monomer having a carboxyl group is not particularly limited. For example, (meth) acrylic acid, maleic acid, fumaric acid, glutaconic acid, itaconic acid, crotonic acid, sorbic acid, cinnamic acid, N- ( (Meth) acryloylglycine, N- (meth) acryloylaspartic acid, N- (meth) acryloyl-5-aminosalicylic acid, 2- (meth) acryloyloxyethyl hydrogen succinate, 2- (meth) acryloyloxyethyl hydrogen phthalate 2- (meth) acryloyloxyethyl hydrogen maleate, 6- (meth) acryloyloxyethylnaphthalene-1,2,6-tricarboxylic acid, O- (meth) acryloyl tyrosine, N- (meth) acryloyl tyrosine, N- (Meth) acryloylphenylalanine N- (meth) acryloyl-p-aminobenzoic acid, N- (meth) acryloyl-o-aminobenzoic acid, p-vinylbenzoic acid, 2- (meth) acryloyloxybenzoic acid, 3- (meth) acryloyloxybenzoic acid Examples include acid, 4- (meth) acryloyloxybenzoic acid, N- (meth) acryloyl-5-aminosalicylic acid, and N- (meth) acryloyl-4-aminosalicylic acid.

  The monomer having a phosphonic acid group is not particularly limited, and examples thereof include phosphooxyethyl (meth) acrylate, 3- (meth) acryloxypropyl-3-phosphonopropionate, and 3- (meth) acryloxy. Propylphosphonoacetate, 4- (meth) acryloxybutyl-3-phosphonopropionate, 4- (meth) acryloxybutylphosphonoacetate, 5- (meth) acryloxypentyl-3-phosphonopropionate 5- (meth) acryloxypentylphosphonoacetate, 6- (meth) acryloxyhexyl-3-phosphonopropionate, 6- (meth) acryloxyhexylphosphonoacetate, 10- (meth) acryloxydecyl -3-phosphonopropionate, 10- (meth) acryloxydecylphosphonoacetate 2- (meth) acryloxyethyl-phenylphosphonate, 2- (meth) acryloyloxyethylphosphonic acid, 10- (meth) acryloyloxydecylphosphonic acid, N- (meth) acryloyl-ω-aminopropylphosphonic acid, etc. Can be mentioned.

  The above monomers can be used alone or in combination of two or more. In addition, in the above, an example in which one functional group is introduced into one monomer has been given. However, a monomer in which two or more positively or negatively charged functional groups are introduced may be used. Good.

  In general, when a substance that biochemically inhibits blood coagulation is present in the surface lubrication layer, the activation of plasma proteins and platelets on the surface of the substrate is suppressed, and the operability of the medical device deteriorates due to the coagulated substance and the living body. Can prevent adverse effects. For this reason, it is preferable that at least one of the hydrophilic polymers (A) and (B) exhibits antithrombotic properties, and it is more preferable that both the hydrophilic polymers (A) and (B) exhibit antithrombogenic properties. .

  Here, examples of the substance that inhibits blood coagulation include heparin and modified heparin into which various functional groups are introduced. Since heparin and modified heparin have a sulfo group, the surface coated with these has a negative charge in an aqueous solution. However, biological materials such as heparin are expensive and difficult to guarantee uniform quality, and there is an unavoidable risk of infection. There are also problems that anticoagulant activity is reduced by sterilization treatment by heating, and that the activity cannot be maintained for a long time due to degradation by enzymes in the living body. For this reason, it is preferable to use artificially synthesized heparinoids that can be synthesized in large quantities at low cost. As the artificially synthesized heparinoid in this case, a hydrophilic polymer having a sulfo group such as poly (2-acrylamido-2-methylpropanesulfonic acid) and polyvinylsulfuric acid and derivatives thereof can be preferably exemplified. These artificially synthesized heparinoids also have a negative charge derived from a sulfo group in an aqueous solution. Further, these substances having a sulfo group can be soluble in various organic solvents, and are excellent in sterilization resistance, unlike biologically derived anticoagulant active substances such as heparin and heparan sulfate.

As described above, a hydrophilic polymer having a structural unit derived from a monomer having a sulfo group exhibits excellent anticoagulant activity (heparin-like activity, antithrombin activity), and therefore includes the hydrophilic polymer. The surface lubricating layer exhibits an excellent antithrombotic action. For this reason, it is preferable that at least one of the hydrophilic polymers (A) and (B) has a negative charge derived from a sulfo group (—SO ₃ H). Thereby, since the hydrophilic polymer itself exhibits antithrombogenicity (physiological anticoagulant action), operability in blood can be maintained for a long time.

  In addition to the monomer having a positively or negatively charged functional group, the hydrophilic polymer according to the present invention may have a structural unit derived from another monomer. Here, it does not restrict | limit especially as another monomer, A well-known monomer can be used. Specifically, salt forms such as sodium salt, potassium salt and ammonium salt of monomer having carboxyl group; monovalent metal salt, divalent metal salt and ammonium salt of monomer having sulfo group And organic amine salts; such as triethylene glycol di (meth) acrylate, (poly) ethylene glycol di (meth) acrylate, polypropylene glycol di (meth) acrylate, (poly) ethylene glycol (poly) propylene glycol di (meth) acrylate, etc. (Poly) alkylene glycol di (meth) acrylates; bifunctional (meth) acrylates such as hexanediol di (meth) acrylate, trimethylolpropane tri (meth) acrylate, trimethylolpropane di (meth) acrylate; triethylene glycol Zimarate, Po (Poly) alkylene glycol dimaleates such as ethylene glycol dimaleate; methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, glycidyl (meth) acrylate, methyl crotonate, ethyl crotonate, propyl crotonate An ester of an unsaturated monocarboxylic acid such as, and an alcohol having 1 to 4 carbon atoms; an amide of an unsaturated monocarboxylic acid and an amine having 1 to 30 carbon atoms such as methyl (meth) acrylamide; styrene, Vinyl aromatics such as α-methylstyrene, vinyltoluene, p-methylstyrene; 1,4-butanediol mono (meth) acrylate, 1,5-pentanediol mono (meth) acrylate, 1,6-hexanediol mono Alkanes such as (meth) acrylate Diol mono (meth) acrylates; dienes such as butadiene, isoprene, 2-methyl-1,3-butadiene, 2-chloro-1,3-butadiene; (meth) acrylamide, (meth) acrylalkylamide, N- Unsaturated amides such as methylol (meth) acrylamide and N, N-dimethyl (meth) acrylamide; Unsaturated nitriles such as (meth) acrylonitrile and α-chloroacrylonitrile; Unsaturated esters such as vinyl acetate and vinyl propionate ; Such as aminoethyl (meth) acrylate, methylaminoethyl (meth) acrylate, dimethylaminoethyl (meth) acrylate, dimethylaminopropyl (meth) acrylate, dibutylaminoethyl (meth) acrylate, vinylpyridine, etc. And saturated amines. These other monomers can be used alone or in combination of two or more. In the case where the hydrophilic polymer further has a constitutional unit derived from another monomer, the amount of the other monomer used detracts from the effect of the monomer having a positively or negatively charged functional group. There is no particular limitation as long as it is not. Preferably, the usage-amount of another monomer is 0.1-50 mass% with respect to all the monomers, More preferably, it is 0.1-20 mass%.

  The method for producing the hydrophilic polymer according to the present invention is not particularly limited, and a known polymerization method can be used. In general, the monomer may be polymerized using a polymerization initiator. The polymerization method of the monomer component is not particularly limited, and can be performed by a method such as polymerization in a solvent or bulk polymerization, for example. When the hydrophilic polymer according to the present invention is a block copolymer or graft copolymer, for example, living polymerization, polymerization using a macromonomer, polymerization using a polymer polymerization initiator, polycondensation However, it is not particularly limited.

  In the present invention, the charge of the hydrophilic polymer (A) is the same as the charge of the hydrophilic polymer (B). For this reason, when the hydrophilic polymers (A) and (B) are produced by appropriately selecting the monomers so that the charges of the hydrophilic polymers (A) and (B) are the same, Good. For this reason, as long as the charges of the hydrophilic polymers (A) and (B) are the same, the types of monomers charged to the charges of the hydrophilic polymers (A) and (B) are the same. Even if the hydrophilic polymers (A) and (B) are produced from the same monomer, these polymers are not necessarily the same. There is no need, and the weight average molecular weight and the like may be different.

[Hydrophilic lubricant coating agent]
The surface lubricating layer according to the present invention may further contain a hydrophilic lubricating coating agent having a reactive functional group in addition to the hydrophilic polymer. In this way, the hydrophilic lubricating coating agent and the hydrophilic polymer having electric charge are formed by mixing the hydrophilic lubricating coating agent and the hydrophilic polymer having electric charge and coating the medical device (base material) to form a surface lubricating layer. It is possible to form a cross-linked structure in the surface lubricating layer by reacting the functional polymer and chemically bonding them. Moreover, if a hydrophilic lubricating coating agent is used, a surface lubricating layer can be easily formed on various substrates according to the type of reactive functional group, and an unreacted reactive functional group and It is possible to react with a hydrophilic polymer having a charge. For this reason, it can suppress and prevent that a surface lubrication layer peels (releases) from a medical device (base material) and a hydrophilic polymer peels (releases) from a surface lubrication layer. Therefore, as in this embodiment, the surface lubricant layer (hydrophilic polymer) is easily and firmly fixed on the surface of the medical device (base material) by using a hydrophilic lubricant coating agent that exhibits good lubricity. Is possible.

  Generally, a reactive functional group (for example, an epoxy group) of a hydrophilic lubricant coating agent reacts with a positively or negatively charged functional group (for example, an amino group, a sulfo group, or a carboxyl group) of a hydrophilic polymer. Therefore, it is difficult to synthesize the copolymer of the monomer constituting the hydrophilic lubricating coating agent and the monomer constituting the hydrophilic polymer so as not to insolubilize. In contrast, when the hydrophilic lubricant coating agent and the hydrophilic polymer are separately prepared and applied to the surface of the medical device (base material) as in the present invention, a large amount of charge can be introduced into the surface. For this reason, by combining these medical devices, even if the medical device 1 is inserted into the medical device 2, an electrostatic repulsive force is generated between them, so that the friction between the medical device 2 and the medical device 1 is generated. Can be effectively reduced. Therefore, the medical device system of the present invention can exhibit excellent operability.

  Therefore, in the present invention, it is preferable that at least one of the surface lubricating layers (A) and (B) further contains a hydrophilic lubricating coating agent, and both the surface lubricating layers (A) and (B) contain a hydrophilic lubricating coating agent. It is more preferable to include further.

  The hydrophilic lubricating coating agent used when the surface lubricating layer further contains a hydrophilic lubricating coating agent is not particularly limited, but has a functional group of the hydrophilic polymer (for example, a positively or negatively charged functional group) and It preferably has a reactive functional group capable of reacting. As a result, the reactive functional group of the hydrophilic lubricant coating agent and the functional group of the hydrophilic polymer react to form a crosslinked structure and insolubilize. When a medical device having such a surface lubricating layer comes into contact with a body fluid or physiological saline, it absorbs water and forms a hydrogel layer on the surface. This hydrogel layer becomes a “surface lubricating layer” that avoids direct contact between the surface of the medical device and the living tissue, and can reduce friction. Therefore, it is preferable that at least one of the surface lubricating layers (A) and (B) has a crosslinked structure, and it is more preferable that both the surface lubricating layers (A) and (B) have a crosslinked structure. As a result, the strength of the surface lubrication layer is improved, and the surface lubrication layer can be prevented (released) from the medical device (base material) and the hydrophilic polymer can be prevented from being separated (released) from the surface lubrication layer. .

  Here, the reactive functional group of the hydrophilic lubricating coating agent is not particularly limited, and is a functional group of a hydrophilic polymer (for example, a functional group of a monomer having a positively or negatively charged functional group). It is appropriately selected depending on the type. Specifically, examples of the reactive functional group include an epoxy group, an acid halide group, an aldehyde group, an isocyanate group, and an acid anhydride group. More preferably, the hydrophilic lubricating coating agent is a polymer compound having an epoxy group and an acid anhydride group as reactive functional groups in the molecule and absorbing 1% or more of water. The expression of surface lubricity occurs when a hydrophilic polymer absorbs an aqueous solvent such as physiological saline, a buffer solution, or blood. Therefore, the hydrophilic polymer in the present invention preferably has a water absorption rate of 100 wt% or more in the temperature range (usually 30 to 40 ° C.) to be used in order to exhibit lubricity.

  In the case where the hydrophilic lubricant coating agent is a polymer compound having a reactive functional group, the polymer compound is not particularly limited, and examples thereof include a polymer compound having a repeating unit derived from a monomer having a reactive functional group. It is done. As the monomer having such a reactive functional group, any monomer having a functional group such as the epoxy group, acid halide group, aldehyde group, isocyanate group, and acid anhydride group may be used. . Specifically, monomers having an epoxy group in the molecule such as glycidyl acrylate, glycidyl methacrylate (GMA), glycidyl ether, methyl glycidyl methacrylate, allyl glycidyl ether; (meth) acrylic acid chloride, (meth) acrylic acid bromide , Monomers having an acid halide group such as (meth) acrylic acid iodide in the molecule; monomers having an aldehyde group in the molecule such as (meth) acrylaldehyde, glyoxal, terephthalaldehyde; acryloyloxyethyl isocyanate, ( A monomer having an isocyanate group in its molecule such as (meth) acryloyloxypropyl isocyanate, 2,2,4-trimethylhexamethylene diisocyanate or 1,3,5-trimethylhexamethylene diisocyanate; Water maleic acid, itaconic anhydride, and the like monomer having an acid anhydride group such as citraconic anhydride in the molecule can be exemplified. Among these, as the monomer having a reactive functional group, a monomer having an epoxy group is preferable, and glycidyl acrylate or glycidyl methacrylate, in which the reaction is accelerated by heat or the like and handling is relatively easy, is more preferable.

  The polymer compound which is a hydrophilic lubricating coating agent may have a constituent unit derived from another monomer in addition to the repeating unit derived from the monomer having the reactive functional group. Here, the other monomer is not particularly limited, and a known monomer can be used, but a hydrophilic monomer is preferable. That is, the polymer compound that is a hydrophilic lubricant coating agent is preferably obtained by copolymerizing a monomer having a reactive functional group in the molecule and a hydrophilic monomer. More preferably, it is a block or graft copolymer in which monomers having reactive functional groups gather to form a reactive domain and hydrophilic monomers gather to form a hydrophilic domain. When such a block or graft copolymer is used, good results are obtained in the strength and lubricity of the surface lubricating layer.

  Such a hydrophilic monomer is not particularly limited, and examples thereof include water-soluble monomers such as acrylamide and derivatives thereof, vinylpyrrolidone, acrylic acid, methacrylic acid, and derivatives thereof. More specifically, N-methylacrylamide, N, N-dimethylacrylamide (DMAA), acrylamide, acryloylmorpholine, N, N-dimethylaminoethyl acrylate, vinylpyrrolidone, 2-methacryloyloxyethylphosphorylcholine, 2- Examples include methacryloyloxyethyl-D-glycoside, 2-methacryloyloxyethyl-D-mannoside, vinyl methyl ether, and the like.

  Monomer having reactive functional group and other monomer when polymer compound as hydrophilic lubricant coating agent is copolymer with monomer having reactive functional group and other monomer The composition with the body is not particularly limited. Considering the formation of the hydrogel layer when it comes into contact with body fluids and physiological saline, and further exhibiting appropriate lubricity, the molar ratio between the monomer having a reactive functional group and the other monomer is The ratio is preferably 1: 1 to 1: 100, and more preferably 1: 5 to 1:20.

  As the polymer compound (hydrophilic lubricating coating agent) according to the present invention, maleic anhydride-methyl vinyl ether copolymer or glycidyl methacrylate-dimethylacrylamide copolymer is preferable, and glycidyl methacrylate-dimethylacrylamide copolymer (especially block copolymer). Polymer) is more preferred. This is because the glycidyl methacrylate-dimethylacrylamide block copolymer is formed by collecting monomers having reactive functional groups to form a reactive domain, and collecting hydrophilic monomers to form a hydrophilic domain. This is because the surface lubricating layer can exhibit good lubricity.

  The method for producing the polymer compound (hydrophilic lubricating coating agent) according to the present invention is not particularly limited, and a known polymerization method can be used. In general, the monomer is added using a polymerization initiator. What is necessary is just to superpose | polymerize. The polymerization method of the monomer component is not particularly limited, and can be performed by a method such as polymerization in a solvent or bulk polymerization, for example. When the polymer compound (hydrophilic lubricant coating agent) according to the present invention is a block copolymer or a graft copolymer, for example, living polymerization, polymerization using a macromonomer, polymer polymerization initiator Examples of the polymerization and polycondensation used are not particularly limited.

[Method of manufacturing medical device system]
In the medical device system of the present invention, at least a part of the outer surface of the medical device 1 is a surface lubricating layer (A) containing the hydrophilic polymer (A), and at least a part of the inner surface of the medical device 2 is highly hydrophilic. As long as it has a structure covered with the surface lubricating layer (B) containing the molecule (B), it may be produced by any method. For example, a hydrophilic polymer is applied to a predetermined surface portion of a medical device. , Spraying device, bar coater, die coater, reverse coater, comma coater, gravure coater, spray coater, method of applying using a doctor knife, etc .; method of immersing medical device in hydrophilic polymer solution Etc. Here, the hydrophilic polymer may be directly applied, but is preferably applied in the form of a solution. At this time, the solvent used for preparing the hydrophilic polymer solution is not particularly limited as long as it can dissolve the hydrophilic polymer. Specific examples include water, methanol, ethanol, isopropanol, acetone, tetrahydrofuran, dimethylformamide, chloroform, and the like. Further, the concentration of the hydrophilic polymer in the solution is not particularly limited, and may be appropriately selected depending on the desired coating amount of the hydrophilic polymer, lubricity, and the like. Preferably, the concentration of the hydrophilic polymer in the solution is 0.1 to 10% by mass, and more preferably 0.2 to 5% by mass.

  As described above, the surface lubricating layer according to the present invention preferably includes a hydrophilic lubricating coating agent having a reactive functional group in addition to the hydrophilic polymer. The manufacturing method of the medical device system in such a case is not particularly limited. That is, the method for applying the hydrophilic polymer and the hydrophilic lubricating coating agent to the medical device (formation method of the surface lubricating layer) is not particularly limited, and the hydrophilic lubricating coating agent and the hydrophilic polymer are mixed. Can be formed by reaction. Here, the application order (mixing order) of the hydrophilic lubricant coating agent and the hydrophilic polymer to the medical device is not particularly limited. Specifically, (a) a method of forming a surface lubricating layer by mixing a hydrophilic lubricant coating agent and a hydrophilic polymer and coating the resulting mixture on a medical device (base material); A medical device (base material) is coated in advance with a hydrophilic lubricating coating agent to form a lubricating coating agent layer, and then the lubricating coating agent layer is impregnated and reacted with a solution of a hydrophilic polymer, preferably a hydrophilic polymer. And (c) forming a hydrophilic polymer layer by previously coating a medical device (base material) with a hydrophilic polymer, and then forming a hydrophilic lubricant coating agent, preferably hydrophilic lubrication. Examples include a method of forming a surface lubricating layer by impregnating and reacting the hydrophilic polymer layer with a solution of a coating agent. Of these, the methods (a) and (b) are preferred. In particular, when the hydrophilic lubricating coating agent and the hydrophilic polymer are not dissolved in the same solvent, the method (a) is preferably used. According to the method (a), since the hydrophilic lubricant coating agent and the hydrophilic polymer are efficiently bonded, it is possible to satisfactorily form a crosslinked structure in the surface lubricant layer. Peeling (releasing) from the tool (base material) and peeling (releasing) of the hydrophilic polymer from the surface lubricating layer can be suppressed and prevented more favorably. Here, the hydrophilic polymer and the hydrophilic lubricating coating agent that react with each other may be dissolved in a solvent separately and mixed immediately before use, or after preparing a mixed solution, the reaction hardly proceeds until used. You may preserve | save on conditions (for example, low temperature). If there is no suitable solvent for dissolving these hydrophilic polymer and hydrophilic lubricant coating agent, the surface of the base material of the medical device may be impregnated separately by changing the solvent. However, in order to form a strong surface lubricating layer, it is preferable to carry out the reaction in a state where the substrate is sufficiently impregnated with the polymer solution. In addition, since it is the same as that of the above or the following about the solvent used for preparation of the hydrophilic polymer and the solution of the said hydrophilic polymer, description is abbreviate | omitted here.

  The hydrophilic lubricating coating agent may be applied as it is, but is preferably applied in the form of a solution. At this time, the solvent used for preparing the solution of the hydrophilic lubricating coating agent is not particularly limited as long as it can dissolve the hydrophilic lubricating coating agent. Specific examples include ethanol, acetone, tetrahydrofuran (THF), dimethylformamide (DMF), chloroform, and the like. Further, the concentration of the hydrophilic lubricating coating agent in the solution is not particularly limited, and can be appropriately selected depending on the desired coating amount, lubricating property, degree of crosslinking, etc. of the hydrophilic lubricating coating agent. Preferably, the concentration of the hydrophilic lubricating coating agent in the solution is 0.1 to 20% by mass, and more preferably 0.5 to 15% by mass.

  When the surface lubricating layer contains a hydrophilic polymer and a hydrophilic lubricating coating agent, the surface lubricating layer is formed by reacting both to form a crosslinked structure and insolubilize. When the surface lubrication layer thus formed comes into contact with body fluid or physiological saline, it absorbs water and forms a hydrogel layer on the surface. This hydrogel layer becomes a “surface lubrication layer” that avoids direct contact between the surface of the medical device and the living tissue, and reduces friction.

  The reaction conditions with the hydrophilic polymer and the hydrophilic lubricating coating agent are not particularly limited as long as both can react with each other. The reaction temperature is preferably 20 to 150 ° C, more preferably 50 to 130 ° C. The reaction time is preferably 1 to 20 hours, and more preferably 2 to 10 hours. Under such reaction conditions, the hydrophilic polymer and the hydrophilic lubricating coating agent can easily react to form a crosslinked structure and insolubilize. In addition to the cross-linking reaction between the hydrophilic polymer and the hydrophilic lubricating coating agent, the above reaction (heat treatment) causes a cross-linking reaction in the hydrophilic lubricating coating agent, and further reacts with the substrate surface of the medical device. In the case of having a reactive functional group that can be reacted, the reaction between the hydrophilic lubricating coating agent and the substrate can also be promoted. That is, the crosslinking reaction is difficult to proceed with the hydrophilic polymer alone, but when combined with the hydrophilic lubricating coating agent, the crosslinking reaction is accelerated and a strong surface lubricating layer can be formed. In addition to heat, a catalyst may be added for the purpose of promoting the reaction. In this case, the catalyst is not particularly limited, and can be appropriately selected depending on the type of the reactive functional group of the hydrophilic lubricating coating agent. For example, when the hydrophilic lubricant coating agent has an epoxy group, a tertiary amine compound such as a trialkylamine compound or pyridine is preferably used. In addition to heat, in order to promote the reaction, light, electron beam, radiation or the like can be used.

  Furthermore, you may perform the process of improving a crosslinked structure further following the said reaction. By improving such a crosslinked structure, the strength of the surface lubricating layer can be further increased while maintaining lubricity. However, if the cross-linked structure is too large, the water swellability is reduced and the low frictional property of the surface is impaired. The method for crosslinking is not particularly limited, and general known methods can be applied. For example, a method of promoting the cross-linking reaction between a hydrophilic polymer and a hydrophilic lubricating coating agent by generating active radicals using light, heat, or radiation, a method of adding a polymerizable polyfunctional monomer, polyfunctionality Examples include a method of applying a crosslinking agent, a method of crosslinking functional groups in a molecule with a catalyst, and the like. The above methods can be combined if necessary.

  The effects of the present invention will be described using the following examples and comparative examples. However, the technical scope of the present invention is not limited only to the following examples.

Reference example 1
The antithrombogenicity of a random copolymer of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and acrylic acid (AAc), which is a hydrophilic polymer according to the present invention, was evaluated as follows.

  Random copolymers of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and acrylic acid (AAc) (AMPS: AAc (molar ratio) = 8: 1) were respectively 25 μg / mL, 50 μg / mL, and 100 μg. / ML and physiological saline solution dissolved at a concentration of 250 μg / mL were prepared, and these were designated as poly (AMPS-AAc) solutions (1) to (4), respectively.

  50 [mu] L of these poly (AMPS-AAc) solutions (1) to (4) and 450 [mu] L of human plasma were mixed, and 50 [mu] L thereof and 50 [mu] L of APTT test drug (Roche PTT reagent "RD") were filled in the cuvette. . Next, these cuvettes were incubated at 37 ° C. for 180 seconds, 50 μL of a 0.025 M CaCl 2 solution was added, and the time until plasma clotting was measured. The results are shown in FIG. As shown in FIG. 4, the plasma clotting time was increased as the poly (AMPS-AAc) concentration was increased. Thus, it was confirmed that poly (AMPS-AAc) has an effect of suppressing blood clotting.

Example 1
A block copolymer (DMAA: GMA (molar ratio) = 12: 1) having dimethylacrylamide (DMAA) as a hydrophilic domain and glycidyl methacrylate (GMA) as a reactive domain is adjusted to a concentration of 8 wt% (dimethylformamide ( A DMF solution dissolved in DMF) was prepared and used as a hydrophilic lubricating coating solution.

  A guide wire (outer diameter 0.36 mm) made of stainless steel coil (SUS304) was immersed in the hydrophilic lubricating coating solution prepared above. Next, after drying this guide wire, it was made to react in 120 degreeC oven for 3 hours, and the hydrophilic lubrication coating layer was formed in the guide wire outer surface.

  Separately, a random copolymer of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and acrylic acid (AAc) (AMPS: AAc (molar ratio) = 8: 1) as a hydrophilic polymer having a negative charge. An aqueous solution dissolved in water was prepared so as to have a concentration of 1 wt%, and this was used as a hydrophilic polymer aqueous solution.

  The guide wire having the hydrophilic lubrication coat layer formed on the outer surface as described above was immersed for 10 minutes in the hydrophilic polymer aqueous solution prepared above. Next, after drying this guide wire, the surface lubrication layer which introduce | transduced the negative charge into the hydrophilic lubrication coating layer was formed by making it react for 4 hours in 120 degreeC oven. Furthermore, in order to remove the unreacted hydrophilic polymer, the guide wire is washed in pure water for one day, and the outer surface of the guide wire is coated with a surface lubricating layer containing a hydrophilic polymer having a negative charge ( A) was obtained. When the cross section of this guide wire (A) was observed with a microscope, the thickness of the surface lubricating layer when wet was about 3 μm and uniform.

Example 2
A stainless steel (SUS304) guide wire (outer diameter 0.36 mm) was immersed in a hydrophilic lubricating coating solution prepared in the same manner as in Example 1 above. Next, this guide wire was dried and then reacted in an oven at 120 ° C. for 7 hours to obtain a guide wire (B) in which a hydrophilic lubricating coating layer was formed on the outer surface of the guide wire. The guide wire (B) has no charge on the outer surface. When the cross section of this guide wire (B) was observed with a microscope, the thickness of the hydrophilic lubricating coating layer when wet was about 3 μm and uniform.

Example 3
The outer surface of a stainless steel (SUS304) guide wire (outer diameter 0.36 mm) was used without being coated, and this was used as a guide wire (C).

Example 4
A block copolymer (DMAA: GMA (molar ratio) = 12: 1) having dimethylacrylamide (DMAA) as a hydrophilic domain and glycidyl methacrylate (GMA) as a reactive domain is adjusted to a tetrahydrofuran (THF) concentration of 10 wt%. A THF solution dissolved in (3) was prepared and used as a hydrophilic lubricating coating solution.

  The hydrophilic lubricating coating solution prepared above was passed through the lumen of a nylon 12 catheter (inner diameter 0.45 mm). Next, after drying this catheter, it was made to react in 100 degreeC oven for 3 hours, and the hydrophilic lubrication coating layer was formed in the catheter inner surface.

  Separately, a random copolymer of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and acrylic acid (AAc) (AMPS: AAc (molar ratio) = 8: 1) as a hydrophilic polymer having a negative charge. An aqueous solution in which the concentration was 1 wt% was prepared, and this was used as a hydrophilic polymer aqueous solution.

  The hydrophilic polymer aqueous solution prepared above was passed for 10 minutes through the catheter having the hydrophilic lubricating coat layer formed on the inner surface. Next, after drying this catheter, the surface lubricating layer which introduce | transduced the negative charge into the hydrophilic lubricating coating layer was formed by making it react in 100 degreeC oven for 7 hours. Furthermore, in order to remove the unreacted hydrophilic polymer, pure water is allowed to flow through the catheter for one day, and a catheter (a) coated with a surface lubricating layer containing a hydrophilic polymer having a negative charge on the inner surface is provided. Obtained. When the cross section of this catheter (A) was observed with a microscope, the thickness of the surface lubricating layer when wet was about 5 μm and uniform.

Example 5
A hydrophilic lubricating coating solution prepared in the same manner as in Example 4 was passed through the lumen of a catheter made of nylon 12 (inner diameter 0.45 mm). Next, after drying this catheter, it was made to react for 10 hours in 100 degreeC oven, and the catheter (b) which formed the hydrophilic lubricous coating layer in the catheter inner surface was obtained. This catheter (b) has no charge on the inner surface. When the cross section of the catheter (b) was observed with a microscope, the thickness of the hydrophilic lubricating coating layer when wet was about 5 μm and uniform.

Example 6
The inner surface of a nylon 12 catheter (inner diameter 0.45 mm) was used as it was without coating, and this was used as the catheter (c).

Example 1, Comparative Examples 1-3: Sliding evaluation Table 1 shows guidewires (A)-(C) of Examples 1-3 and catheters (a)-(c) of Examples 4-6. Thus, the slidability of these combinations was evaluated by the following procedure.

  As shown in FIG. 2, the catheters of medical device systems 1 to 4 having a length of 250 mm each having a hub attached to the tip were fixed in a tube made of vinyl chloride fixed in a loop shape of φ35 mm. In this state, the inside of the tube made of vinyl chloride was filled with fresh blood (including heparin 0.75 units / mL). Fresh blood was sucked from the hub attached to the catheter, and it was confirmed that the inside of the catheter and the hub were filled with fresh blood. The guide wires of the medical device systems 1 to 4 were sufficiently moistened with physiological saline and then inserted from the hub side of each catheter. After the guide wire was quickly connected to the push-pull gauge, the catheter was reciprocated up and down 30 times in the width of 20 mm at a speed of 100 mm / min. The slide resistance of the guide wire / catheter system was evaluated by recording the sliding resistance value measured by the push-pull gauge while the catheter was reciprocated. The measurement results are shown in FIG.

  The following is considered from FIG. That is, it can be seen that the medical device system 1 of Example 1 exhibited a low sliding resistance value from the beginning of sliding and maintained that value for 30 reciprocations. It is considered that this is because the electrostatic repulsive force acts between both surfaces due to the negative charge existing on the outer surface of the guide wire and the inner surface of the catheter, and the friction is reduced, so that a low sliding resistance value is exhibited. Moreover, since the surface lubricating layer has antithrombotic properties, it was possible to suppress the formation of microthrombi and to maintain stable lubricity for a long time.

  In contrast, the medical device system 4 of Comparative Example 3 shows a high sliding resistance value from the beginning, and it can be seen that the value increased remarkably as the sliding was repeated. This is because SUS304 on the outer surface of the guide wire and nylon 12 on the inner surface of the catheter are materials that can induce thrombus formation, so that the thrombus formed on the guide wire or the catheter surface becomes an obstacle to sliding, and the sliding resistance value This is thought to be due to an increase in.

  Moreover, the medical device system 2 of Comparative Example 1 showed a relatively low sliding resistance value, and no significant increase in the sliding resistance value was observed even when sliding was repeated. This is because the hydrophilic lubrication coat coated on the outer surface of the guide wire and the inner surface of the catheter is a material that hardly induces the adsorption of plasma proteins and platelets. This is thought to be because it has not been reached. However, when in contact with blood for a long time, the coagulation factor activated on the surface formed microthrombus and the sliding resistance was slightly increased. This is because the outer surface of the guide wire B and the inner surface of the catheter b are both coated with a lubricating layer having no electric charge, so that no electrostatic repulsive force acts between both surfaces, and the sliding resistance value is high. It is thought that it became.

  Furthermore, the medical device system 3 of Comparative Example 2 showed a relatively low sliding resistance value, and no significant increase in the sliding resistance value was observed even when sliding was repeated. However, the sliding resistance value was almost equivalent to that of Comparative Example 1. This is because the outer surface of the guide wire A is covered with a lubricating layer having a negative charge, but the inner surface of the catheter b is covered with a lubricating layer having no charge, so that an electrostatic repulsive force is formed between both surfaces. It is considered that the sliding resistance value was still high.

  From the above results, by forming an anti-thrombogenic surface lubricating layer that acts electrostatic repulsion between the inner surface of the catheter and the outer surface of the guide wire, it exhibits excellent operability that has not been achieved in blood vessels, It is possible to realize a medical device system for endovascular treatment that can suppress a decrease in operability due to thrombus formation and maintain good operability for a long time.

Claims (6)

A medical device system having a hollow first medical device and a second medical device inserted into the first medical device,
The inner surface of at least a part of the first medical device is coated with a first surface lubricating layer containing a first hydrophilic polymer having a charge,
At least a part of the outer surface of the second medical device is coated with a second surface lubricating layer containing a second hydrophilic polymer having the same sign as the charge of the first hydrophilic polymer. A medical device system. 2. The at least one of the first hydrophilic polymer and the second hydrophilic polymer has a negative charge derived from a sulfo group (—SO ₃ H) or a carboxyl group (—COOH). Medical tool system.   The medical device system according to claim 1 or 2, wherein at least one of the first hydrophilic polymer and the second hydrophilic polymer exhibits antithrombogenicity.   The medical device system according to any one of claims 1 to 3, wherein at least one of the first surface lubricating layer and the second surface lubricating layer has a crosslinked structure.   At least one of the first surface lubricating layer and the second surface lubricating layer is formed by mixing and reacting a hydrophilic lubricating coating agent having a reactive functional group and a hydrophilic polymer having a charge. The medical device system according to any one of claims 1 to 4.   At least one of the first surface lubricating layer and the second surface lubricating layer has a charge after a medical device is coated with a hydrophilic lubricating coating agent having a reactive functional group in advance to form a lubricating coating agent layer. The medical device system according to claim 5, wherein the medical device system is formed by impregnating the lubricating coating agent layer with a hydrophilic polymer to cause a reaction.