JP3586869B2 - Guide wire manufacturing method - Google Patents

Description

[0001]
[Industrial applications]
The present invention relates to a method for manufacturing a guide wire used when inserting a catheter or the like into a tubular organ of a human body such as a blood vessel, a ureter, or a trachea.
[0002]
[Prior art]
In recent years, when administering drugs to blood vessels, ureters, trachea, etc., or inserting dilators (stents), a technique has been adopted in which a catheter or the like is inserted percutaneously without incising the affected part. Have been. When inserting a catheter into an affected part, a method of first inserting a guide wire and sliding along the guide wire to insert the catheter is often used.
[0003]
As the guide wire, a thin wire made of a metal such as stainless steel or a shape memory alloy is coiled to have flexibility, and a wire made of the above metal is used as a core wire and its outer periphery is made of a synthetic resin film or the like. Various types have been proposed, such as those covered with.
[0004]
The guide wire must be capable of being inserted securely into the affected part without damaging the tissue when inserted into a tissue such as a blood vessel, a ureter, and a trachea, and a catheter that can be inserted by sliding a catheter. However, with a guide wire in which the outer periphery of the core wire is coated with a synthetic resin film, the insertion operation may be difficult due to frictional resistance between the inner surface of the catheter and the guide wire.
[0005]
In order to solve such a problem, Japanese Patent Publication No. 59-19582 discloses a method in which a first coating layer of polyurethane having a non-reactive isocyanate group is formed on the surface of a substrate, and the surface is reacted with polyvinylpyrrolidone. A substrate (support) is disclosed in which a second coating layer chemically bonded to the non-reactive isocyanate group is formed so that the surface has lubricity when wet.
[0006]
[Problems to be solved by the invention]
However, in the method disclosed in Japanese Patent Publication No. 59-19582, the adhesiveness between the coating layer and the base material is low. Have a problem that the lubricating oil tends to fall off, and the lubricity decreases with repeated use.
[0007]
Accordingly, an object of the present invention is to provide a method for manufacturing a guide wire in which a synthetic resin film is coated on the outer periphery of a core wire and a hydrophilic film is formed on the surface of the synthetic resin film so that the lubricity does not decrease even when repeatedly used. It is to provide a manufacturing method of a guide wire over which the.
[0008]
[Means for Solving the Problems]
In order to achieve the above object, a method for manufacturing a guide wire according to the present invention is a method for manufacturing a guide wire, in which a synthetic resin film is coated on the outer periphery of a core wire and a hydrophilic film is formed on the surface of the synthetic resin film.
The outer periphery of the core wire is coated with a synthetic resin having an isocyanate group remaining, or is coated with a synthetic resin having reactivity with an isocyanate group, and then is reacted with a compound having an isocyanate group, so that the surface of the synthetic resin is coated. After forming unreacted isocyanate groups,
Polyvinylpyrrolidone is crosslinked, benzoyl peroxide, hydrogen peroxide, and the reaction of polyvinylpyrrolidone with the unreacted isocyanate group in the presence of a material selected from persulfate , or polyvinylpyrrolidone with the unreacted After reacting with the isocyanate group of the above, the above-mentioned material for cross-linking polyvinylpyrrolidones is caused to act.
[0010]
Hereinafter, the present invention will be described in detail with reference to preferred embodiments.
[0011]
In the present invention, as the core wire, for example, in addition to metals such as shape memory alloys, stainless steel, and piano wires, thermoplastic resins, resins such as FRP, or composites of metals and resins can also be used. Both are not particularly limited. The core wire preferably has moderate rigidity on the base side and sufficient flexibility on the distal end.
[0012]
Further, the synthetic resin film covering the outer periphery of the core wire is a resin in which unreacted isocyanate groups remain so that polyvinylpyrrolidone (hereinafter abbreviated as PVP) can be bonded to the surface thereof via isocyanate groups. Or a resin having reactivity with a compound having an isocyanate group.
[0013]
As the resin in which the isocyanate group remains, for example, a polyurethane resin in which a polyhydric alcohol is reacted with an excess of diisocyanate to leave a free isocyanate group at a terminal is preferably used.
[0014]
Further, as the resin having reactivity with the compound having an isocyanate group, for example, a polyurethane-based, polyamide-based, polyvinyl chloride-based, polyester-based, latex-based resin, or the like can be used.
[0015]
As the synthetic resin film, when a resin having an isocyanate group remaining is used, PVP can be reacted as it is. However, when another resin is used, a compound containing an isocyanate group is bonded to the surface of the resin. Need to form unreacted isocyanate groups. When a resin having an isocyanate group remaining is used, a compound having an isocyanate group may be further bonded as necessary.
[0016]
In order to bond the compound having an isocyanate group to the surface of the synthetic resin film, the compound may be brought into contact with a solution containing the compound having an isocyanate group to cause a reaction. As a method for bringing a solution containing a compound having an isocyanate group into contact with the surface of the synthetic resin film, a method such as immersion, brush painting, or spinner coating is employed.
[0017]
As the compound having an isocyanate group, for example, diphenylmethane diisocyanate, hexamethylene diisocyanate, xylene diisocyanate, naphthalene diisocyanate, triphenylmethane diisocyanate, toluylene diisocyanate and the like are preferably employed.
[0018]
As a solvent for dissolving the compound having an isocyanate group, methyl ethyl ketone, tricrene and the like are preferable. The concentration of the compound having an isocyanate group in the solution is preferably 5 to 20% by weight, and the time for contacting the solution with the surface of the synthetic resin film is preferably 30 to 90 seconds.
[0019]
If the surface of the synthetic resin film is treated with a solvent that swells the resin before the solution containing the compound having an isocyanate group is brought into contact with the solution and the resin surface is washed and activated, the isocyanate group is easily bonded. It is preferable. The time for treating with these solutions is preferably about 20 to 40 seconds. As the solvent, methyl ethyl ketone or a chlorinated organic solvent such as trichlene or chloroform is preferable, and among them, methyl ethyl ketone is particularly preferable.
[0020]
After an unreacted isocyanate group is formed on the surface of the synthetic resin film as described above, an organic solvent solution of PVP is brought into contact, and PVP is graft-bonded via the isocyanate group. In this case, in the present invention, it is preferable to use PVP having a molecular weight of 10,000 to 2,000,000.
[0021]
The concentration of the PVP solution is preferably 1 to 10% by weight, more preferably 2 to 5% by weight. The organic solvent used for the PVP solution is preferably a chlorine-based organic solvent, for example, dichloromethane, chloroform, or the like.
[0022]
In the present invention, a material selected from benzoyl peroxide, hydrogen peroxide, and persulfate is used as a material for crosslinking PVP, and benzoyl peroxide is particularly preferable.
[0023]
The material for cross-linking the PVP may be added to and mixed with the PVP solution, or the surface of the synthetic resin film may be treated with the PVP solution, and then the material alone may act on the surface. . The amount of the above- mentioned material added and mixed in the PVP solution is preferably 1 to 5% by weight, more preferably 1 to 2% by weight, based on the PVP solution.
[0024]
As a method of bringing the PVP solution into contact with the synthetic resin film having an isocyanate group formed on the surface, any method such as immersion, brush painting, or spinner coating may be used. After the PVP solution is applied in this manner, it is allowed to stand at 60 to 100 ° C. for 3 hours or more to react, whereby PVP can be graft-bonded to the surface of the synthetic resin film via an isocyanate group.
[0025]
At this time, when a material for cross-linking the PVP is added to the PVP solution, the PVP molecules can be graft-bonded and the PVP molecules can be cross-linked . When the above materials are not added to the PVP solution, the PVP molecules are treated with a solution containing the above materials after the treatment with the PVP solution, whereby the PVP molecules can be cross-linked .
[0026]
After binding the PVP in this manner, it is preferable to remove the compound having excess isocyanate groups and unbound PVP by performing a water treatment. Further, by performing the water treatment, the PVP molecules can be loosened and the hydrophilicity can be improved. The water treatment is preferably performed for 6 hours or more.
[0027]
The treatment with the PVP solution can be repeated twice or more as necessary. In particular, the lubricating property can be further improved by coating twice at the tip of the guide wire.
[0028]
[Action]
The guide wire of the present invention has a hydrophilic coating formed by bonding PVP via an isocyanate group to the surface of a synthetic resin film covering the outer periphery of a core wire and crosslinking the PVP molecules.
[0029]
PVP is a hydrophilic polymer, which swells by capturing water molecules between molecular chains, and thus exhibits excellent lubricity when inserted into the body. In addition, PVP is non-reactive with living tissues and has excellent antithrombotic properties.
[0030]
Further, in the present invention, since the PVP molecules are mutually cross-linked on the synthetic resin film, the polymer is prevented from falling off during use, and excellent lubricity can be maintained even after repeated use.
[0031]
【Example】
Example 1
FIG. 1 shows an embodiment of a guide wire according to the present invention. In the figure, a core wire 1 is made of a stainless steel wire having a diameter of 0.35 mm and a length of 1600 mm, and a portion 100 mm from the tip is machined in a tapered shape. The outer periphery of the core wire 1 is covered with a synthetic resin film 2 made of polyurethane which is extruded and formed integrally with the core wire 1. Further, a hydrophilic film 3 formed by the method of the present invention is provided on the surface of the synthetic resin film 2. This guide wire is made to have a diameter of 0.89 mm and a length of 1600 mm as a whole.
[0032]
In addition, as the core wire 1, various materials such as a piano wire, an amorphous alloy, a hard synthetic resin, and FRP can be used in addition to stainless steel. Usually, the diameter of the core wire 1 is preferably 0.05 to 1.0 mm. As described above, as the synthetic resin film 2, a synthetic resin having an isocyanate group remaining or having reactivity with the isocyanate group can be used. The size of the guide wire is generally 100 to 3000 mm in total length, preferably 450 to 1800 mm, and an outer diameter of 0.25 to 1.5 mm.
[0033]
The hydrophilic coating 3 is formed as follows. First, the outer periphery of the core wire 1 is coated with a synthetic resin film 2 made of polyurethane (trade name "Esten", manufactured by Kyowa Hakko Co., Ltd.), and then dipped in a 5% by weight methyl ethyl ketone solution of 4,4-diphenylmethane diisocyanate for 60 seconds. Unreacted isocyanate groups are formed on the surface of the synthetic resin film 2 by allowing the mixture to react at 60 ° C. for 30 minutes.
[0034]
Next, it was immersed in a dichloromethane solution containing 2% by weight of PVP having a molecular weight of 1.2 million (trade name "K-90", manufactured by Wako Pure Chemical Industries, Ltd.) and 1% by weight of benzoyl peroxide for 5 seconds. After standing for a period of time, PVP is bonded to unreacted isocyanate groups and PVP molecules are mutually cross-linked . Finally, it is immersed in pure water for 15 hours to perform water treatment, and dried at 60 ° C. for 24 hours to obtain a product.
[0035]
The guide wire thus obtained is used by moistening its surface with water at the time of use. This guide wire has excellent lubricity due to the hydrophilic coating 3 formed on the surface of the synthetic resin film 2 and reduces the friction between the guide wire and the catheter. It was possible to easily perform the insertion operation into the device.
[0036]
Comparative Example 1
A guide wire having a hydrophilic coating was obtained in the same manner as in Example 1, except that a dichloromethane solution containing 2% by weight of PVP and not containing benzoyl peroxide was used. Was.
[0037]
Example 2
After coating a synthetic resin film made of urethane (trade name "Esten", manufactured by Kyowa Hakko Co., Ltd.) on the outer periphery of the same core wire as in Example 1, immersed in a 5% by weight methyl ethyl ketone solution of 4,4-diphenylmethane diisocyanate for 60 seconds. Then, unreacted isocyanate groups were formed on the surface of the synthetic resin film by allowing the mixture to react at 60 ° C. for 30 minutes.
[0038]
Next, it was immersed in a dichloromethane solution containing 2% by weight of PVP having a molecular weight of 1.2 million (trade name “K-90”, manufactured by Wako Pure Chemical Industries, Ltd.) for 5 seconds and air-dried. Then, it was immersed in a dichloromethane solution containing 1% by weight of benzoyl peroxide for 5 seconds, and allowed to stand at 60 ° C. for 6 hours to bond PVP to unreacted isocyanate groups and crosslink PVP molecules mutually. Finally, it was immersed in pure water for 15 hours to perform water treatment, and dried at 60 ° C. for 24 hours to obtain a guide wire having a hydrophilic film.
[0039]
Comparative Example 2
A hydrophilic film was prepared in the same manner as in Example 2 except that the process of Example 2 was repeated twice with a dichloromethane solution containing 2% by weight of PVP and not containing benzoyl peroxide. Was obtained.
[0040]
Test Example After the guide wires obtained in Examples 1 and 2 and Comparative Examples 1 and 2 were respectively wetted with water, they were passed through a catheter having an inner diameter of 0.99 mm (4.3 Fr) formed into a loop having a diameter of 50 mm. After passing repeatedly, the relationship between the number of passes and the frictional resistance was examined. The result is shown in FIG.
[0041]
The coefficient of friction was measured using the apparatus shown in FIG. That is, after placing the water 12 in the water tank 11 and arranging the sample 13 on the bottom thereof, the contact 14 is pushed in the direction of the arrow a so that the contact 13 is pressed against the sample 13 with a load of 300 g. The coefficient of friction when the contact 14 was moved in the direction of arrow b was measured.
[0042]
In FIG. 2, curves A, B, C, and D are the results for the guide wires obtained in Example 1, Comparative Example 1, Example 2, and Comparative Example 2, respectively. The coefficient of friction at the start of the test was 0.028 for all of A, B, C, and D, while the coefficient of friction at the time of passing 100 times through the catheter was 0.047 for A, 0.07 for B, and C for C. Was 0.028 and D was 0.045. From the above results, the product of the example in which the PVP film crosslinked with benzoyl peroxide was formed, the increase in the coefficient of friction against repeated use was significantly suppressed as compared with the product of the comparative example in which the PVP film not crosslinked was formed. I found out.
[0043]
【The invention's effect】
As described above, according to the guide wire of the present invention, the outer periphery of the core wire is coated with the synthetic resin film, and PVP is bonded to the surface of the synthetic resin film via the isocyanate group, so that the lubricity when wet is improved. Excellent, the frictional resistance between the guide wire and the catheter can be extremely reduced. Further, since the PVP molecules are cross- linked to each other, the lubricity does not decrease even when repeatedly used, and the durability can be improved.
[Brief description of the drawings]
FIG. 1 is a sectional view showing one embodiment of a guide wire of the present invention.
FIG. 2 is a chart showing a change in a coefficient of friction when the guide wires of Examples and Comparative Examples of the present invention are repeatedly used.
FIG. 3 is a schematic sectional view of an apparatus for measuring a coefficient of friction.
[Description of sign]
Reference Signs List 1 core wire 2 synthetic resin film 3 hydrophilic coating

Claims (3)

In a method of manufacturing a guide wire in which a synthetic resin film is coated on an outer periphery of a core wire and a hydrophilic film is formed on a surface of the synthetic resin film,
The outer periphery of the core wire is coated with a synthetic resin having an isocyanate group remaining, or is coated with a synthetic resin having reactivity with an isocyanate group, and then is reacted with a compound having an isocyanate group, so that the surface of the synthetic resin is coated. After forming unreacted isocyanate groups,
Polyvinylpyrrolidone is cross-linked, benzoyl peroxide, hydrogen peroxide, and reacting polyvinylpyrrolidone to the unreacted isocyanate group in the presence of a material selected from persulfate , or polyvinylpyrrolidone is unreacted And reacting the isocyanate group of the above with a material for crosslinking polyvinylpyrrolidone with each other. The method for producing a guide wire according to claim 1, wherein the molecular weight of the polyvinylpyrrolidone is 10,000 to 2,000,000. The method for producing a guidewire according to claim 1 or 2, wherein benzoyl peroxide is used as a material for crosslinking the polyvinylpyrrolidones.

Images