JP2010046179A - Catheter guide wire - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a catheter guide wire having wettability to be used when the catheter guide wire, especially for treatment and examination, is introduced into a required region of a body cavity such as a blood vessel, trachea, or digestive tract. <P>SOLUTION: The catheter guide wire has a metal core composed of a center wire 2 made of metal with small elastic modulus, and a coating material made of metal with large elastic modulus to coat the center wire. The distal end of the metal core is tapered, and a coating layer 4 is disposed on the surface of the metal core. In the coating layer 4, hydrophilic macromolecules of a cross-linkage structure having wettability when wetted are chemically combined. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

The present invention relates to a catheter guide wire, and more particularly to a catheter guide wire having wettability, which is used when a therapeutic or examination catheter is introduced to a required part of a body cavity such as a blood vessel, trachea, and digestive tract.

Conventionally, when a therapeutic or examination catheter is introduced to a predetermined site in a body cavity such as a blood vessel, trachea, and digestive tract, a catheter guide wire is introduced to the predetermined site prior to the introduction of the catheter. The guide wire for catheter is usually provided with a protective coating made of synthetic resin on a metal core as required.

Catheter guidewires usually have the following characteristics: (1) The tip is sufficiently flexible so that the body wire is not damaged by the introduction of the guide wire. (2) The tip is adapted to shape in order to be introduced along the meandering and branching body cavity. (3) The elastic modulus at the tip is sufficiently small
On the other hand, when a guide wire is introduced, it is important that the base end portion is excellent in motion transferability such as rotation because the base end portion is operated to control the traveling direction of the tip end portion. Therefore, the elastic modulus of the material of the base end portion needs to be relatively large. In addition, it is necessary to minimize damage to the inner wall of the body cavity and mucous membrane when the guide wire is introduced.

The applicants of the present application have proposed a guide wire for a catheter excellent in the above three characteristics and operability of the guide wire in Japanese Patent Laid-Open No. 2003-24445 (Patent Document 1). Such a guide wire includes a center wire and a metal core made of a covering material coated on the center wire, and the center wire is formed of a metal having a relatively small elastic modulus, and the covering material has a relatively large elastic modulus. It is a guide wire for catheters, which is made of metal, the tip of the metal core is tapered and only made of hollow wire, and the metal core is coated with synthetic resin protective coating, and it is manufactured without significant increase in manufacturing cost. In spite of being able to do so, the elastic modulus of the distal end portion can be made sufficiently small, and the elastic modulus of the proximal end portion can be made within a required range.

The catheter guide wire proposed in Patent Document 1 is an excellent guide wire having the above characteristics of the guide wire, but when introducing the guide wire into the body cavity, polyurethane and flexible are used to improve lubricity. The surface of the metal core is covered with a protective film made of a synthetic resin such as a polyolefin polymer. However, if a polymer such as polyurethane is coated directly on the metal surface, the polymer may peel off or fall off, and the lubricity will be poor. There was a problem in practical use because it was sufficient. In order to solve the above problems of these polymers, a metal surface of a guide wire is coated with an adhesive organic compound having a functional group that chemisorbs to at least one metal in the molecule and at least one reactive functional group. JP-A-2007-267757 (Patent Document 2) discloses a method of coating a polymer on the surface, but even in this method, if the surface of the polymer is lightly rubbed by hand, the polymer can be easily peeled off and dropped off. Can not.
JP2003-24445 JP2007-267757

Accordingly, an object of the present invention is to provide a catheter guide wire that can reliably reach a predetermined site in a body cavity and has excellent flexibility and durability and lubricity.

As a result of thorough examination of the problems of the conventional guide wire, the present inventors have excellent flexibility and durability and lubricity by coating a specific hydrophilic resin on the surface of the metal core. The present inventors have found that a guidewire for a catheter can be provided and have reached the present invention.
That is, the present invention comprises a metal core composed of a center wire made of a metal having a low elastic modulus and a cover made of a metal having a high elastic modulus that covers the center wire, and has a tapered tip. A catheter guide wire comprising a coating layer in which a hydrophilic polymer having a crosslinked structure wettable when wet is chemically bonded to the surface of a metal core formed into a shape.

The guide wire for a catheter of the present invention includes a metal core having a center wire and a covering material coated on the center wire, the center wire being formed of a metal having a low elastic modulus, and the covering material has an elastic modulus. Since it is made of a large metal and contains a covering material other than at least the base end of the metal core, it can be manufactured without a significant increase in manufacturing cost and the elastic modulus of the tip is reduced. And the elastic modulus of the base end can be set within a predetermined range.
In addition, it does not form an intermediate coat layer by inserting metal into an extruded tube (thickness of several tens to several hundreds of μ) such as polyurethane resin or polyamide resin as in the case of conventional guidewires. By providing a coating layer chemically bonded with a hydrophilic polymer with a crosslinked structure that has wettability when wet by the direct coating method, the coating layer can be made thin and excellent in lubricity and lubrication durability It has become possible to provide a catheter guide wire that can be easily inserted into a body cavity.

Next, an embodiment of the catheter guide wire according to the present invention will be described with reference to the drawings. As shown in FIG. 1, the catheter guide wire of the present invention is composed of a center wire 6, a metal core 2 made of a covering material 8 covered with the center wire, and a covering layer 4 made of a hydrophilic polymer. . The center wire 6 is continuously extended from the proximal end 2a to the distal end 2b of the metal core 2. The cross section of the center wire 6 is circular. It is important that the center wire 6 is made of a metal having a small elastic modulus. As a metal for forming the center wire 6, an alloy having super elasticity such as a Ni-Ti alloy, a Cu-Zn-Al alloy, a Cu-Al-Mn alloy, or a Fe-Mn alloy is adopted. be able to. On the other hand, the covering material 8 covered with the center wire 6 is formed of a metal having a relatively large elastic modulus. As the metal forming the covering material 8, stainless steel or copper-based metal is usually employed. The cross section of the covering material 8 covered with the center wire 6 is annular.

The metal core 2 includes a base end portion 10 and a tip end portion 12 as well as an intermediate portion 14 existing between the base end portion 10 and the tip end portion 12. As shown in the enlarged view of the tip portion in FIG. 2, it is important that the tip member 12 of the metal core 2 does not have the covering material 8 and the tip portion 12 is formed only of the center wire 6. At the tip 12 of the metal core 2, the center wire 6 is gradually tapered. At the forefront of the intermediate portion 14, the thickness of the covering material 8 is substantially zero, and at the end of the intermediate portion 14, the thickness T1 of the covering material 8 is usually 0.05 to 0.4 mm. The thickness T2 of the covering material 8 is uniform at the base end portion 10 of the metal core 2, and is substantially the same as the thickness T1 at the rearmost end of the intermediate portion. 4 is a coating layer made of a hydrophilic polymer.

The length of the tip 12 of the metal core 2 is 10 to 400 mm, usually 100 to 300 mm. The length of the base end portion 10 is 500 mm or more, usually 700 to 800 mm. The length of the intermediate part 14 is 50 to 700 mm, usually 100 to 600 mm. The elastic modulus of the metal core 2 composed of the center wire 6 and the covering material 8 is that the tip 12 is not more than 0.6 kgf of fruit juice when the deflection is 0.8 mm in a three-point bending test with a spacing of both support points of 14 mm. 0.4kgf or less. In the guide wire of FIG. 2, the center wire 6 is gradually tapered at the distal end portion 12, so that the elastic modulus gradually decreases toward the distal end 2b. The base end portion 10 is a base end with a load of 0.7 kgf or more, usually from 0.8 to a sum of 0.8 when the deflection is 0.8 mm in a three-point bending test with a sense of both support points of 14 mm. The elastic modulus of the base end 10 is constant. Since the covering material 8 is gradually tapered at the intermediate portion 14, the elastic modulus gradually decreases toward the tip portion 12.

The metal core 2 can be manufactured as follows. A center wire 6 having an outer diameter D2 is prepared, and a tubular covering material 8 is inserted through the center wire 6. The inner diameter of the covering material 8 at the time of insertion may be sufficiently larger than the outer diameter of the center wire 6. Next, the covering material 8 is stretched in the length direction to gradually reduce the outer diameter and the inner diameter, the inner peripheral surface of the covering material 8 is brought into close contact with the outer peripheral surface of the center wire 6, and the covering material 8 is firmly attached to the center wire 6. To be joined. As shown by a two-dot chain line in FIG. 3, the thickness of the center wire 8 is substantially constant over the entire length from the base end 2a to the tip end 2b of the metal core 2 thus formed. Thereafter, the tip portion 12 and the intermediate portion 14 of the metal core 2 are cut away by cutting to remove the portion indicated by the two-dot chain line.
Further, when the tip end side of the metal core in a state where the covering material is in close contact with the center wire is further stretched to reduce the diameter, a guide wire having a very thin metal core on the tip side and a soft tip can be manufactured. . When the diameter of the metal core is reduced stepwise from the front end side to the rear end, a catheter guide wire having optimum flexibility can be provided.

The guide wire shown in FIG. 2 may not be flexible enough to introduce the guide wire to a predetermined site, but in that case, the tip side of the metal core as described above is thinned to be flexible. In addition to the method for improving the flexibility, the flexibility of the tip can be improved by inserting the coil spring body 15 into the tip of the metal core of the guide wire. As shown in FIG. 4, a coil spring body 15 is inserted into the distal end portion 12 of the metal core 2. The coil spring body 15 may be a coil made of one type of metal or a coil in which coils made of a plurality of types of metals are connected and integrated. Usually, a coil made of two kinds of metals is connected and integrated. As shown in FIG. 4, the second coil 17 disposed on the rear end side and the first coil 16 disposed on the front end side of the second coil 17 are joined and integrated. The coil spring body 15 covers the entire length of the distal end portion 12 of the metal core 2, and is usually the same length as the length 10 to 400 mm of the distal end portion 12 of the metal core 2 or slightly longer. The outer diameter of the coil spring body 15 is usually slightly larger than the outer diameter of the center wire 6. In FIG. 4, the outer shape of the coil spring body 15 is the same from the front end to the rear end. The rear end of the second coil 17 disposed on the rear end side is joined to the covering material 6. On the other hand, the tip of the first coil is joined to the tip of the center wire.

Examples of the material of the coil spring body 15 include noble metals such as gold and platinum, or alloys containing them (for example, gold-iridium alloy). In particular, when configured with a radiopaque material such as a noble metal, X-ray contrast is obtained in the guide wire, and it can be inserted into the blood vessel while confirming the position of the tip under fluoroscopy, preferable. Such noble metals are typically used for the first coil 16. The second carp 17 may be made of a material different from that of the first coil 16. For example, the first coil 16 may be made of a coil made of an X-ray opaque material, and the second coil 17 may be made of a coil made of a material that relatively transmits X-rays (for example, stainless steel).

By inserting such a coil spring body 15 into the distal end portion of the guide wire, the distal end portion 12 of the guide wire is covered with the coil and has a small contact area, so that the sliding resistance can be reduced. The operability of the guide wire is improved.
The first coil 16 and the second coil 17 constituting the coil spring body 15 are preferably joined and fixed by welding. Thereby, a high joining strength can be obtained at the joining portion between the first coil and the second coil by a simple method.

On the other hand, the outer diameter of the coil spring body 18 of the guide wire shown in FIG. 5 gradually decreases in the distal direction. By having such an outer diameter gradually decreasing portion, the rigidity of the coil spring body 18 made of platinum wire provided at the distal end portion can be gradually decreased toward the distal end direction. Good flexibility can be obtained at the distal end portion, the followability to blood vessels and safety can be improved, and bending and the like can also be prevented.

As shown in FIG. 4, the surface of the metal core 2 of the guide wire and the coil spring body 15 is provided with a coating layer 4 in which a hydrophilic polymer having a crosslinked structure that has wettability when wet is chemically bonded. Yes. The coating layer 4 is obtained by treating the surfaces of the metal core 2 and the coil spring body 15 with a sulfur-containing compound, and then reacting a hydrophilic compound and a crosslinking agent on the surface to directly fix the hydrophilic polymer on the surface of the metal core. ing. In the present invention, the sulfur-containing compound used for chemically fixing the hydrophilic compound on the surface of the metal core 2 has a functional group capable of forming a bond between a metal and a sulfur atom, and the hydrophilic compound. A compound having at least one functional group capable of reacting with the compound is preferably used. The sulfur compound is a compound represented by the general formula (X) n-R- (Y) m, wherein X is a functional group containing a sulfur atom reactive with a metal, and Y is hydrophilic. It is a functional group having reactivity with the active compound. n and m are each an integer from 1 to 10, and R is an organic residue. X is selected from the group consisting of thiol group, sulfide group, polysulfide group, sulfoxide group, thioketone group, thioaldehyde group, thioacetal group, thiocarboxyl group, thiophosphate group, thiocarbonate group, thiirane group, and thiolane group. It contains at least one sulfur-containing functional group. Y represents at least one functional group selected from the group consisting of thiol group, hydroxyl group, amino group, isocyanate group, alkoxysilane group, silanol group, carboxyl group, acrylic group, epoxy group, and acid anhydride group. Although X and Y are not limited to these, formation of a chemical bond between a metal and a sulfur compound and formation of a chemical bond between a sulfur compound and a hydrophilic compound in the present invention can be achieved. Any compound having a functional group can be used.

Specific examples of the compound include various triazine thiol derivatives and various pyrimidine thiol derivatives. For example, 1,3,5-triazine-2,4,6-trithiol, 1,3,5-triazine-2,4,6-trithiol monosodium salt, 2,4-dimercapto 1,3-pyrimidine group Derivatives, and the like. These compounds may be “thiol type” or “thione type”. A compound having a thiol group has a problem in storage stability, but these compounds have excellent storage stability because they have a “thiol-type” and “thione-type” tautomer. In addition, compounds having four thiols such as tetramercaptobiphenyl and pentaerythritol tetrakismercaptopropionate, thiol groups such as cysteine, thioglycerol, 3-mercaptopropyltrimethoxysilane, and other functional groups And compounds having a disulfide group such as 4-aminophenyl disulfide, α-lipoic acid, cystine, and other functional groups.

Further, before the surface of a metal such as stainless steel or nickel / titanium alloy is treated with a sulfur-containing compound, the effect of the present invention is further improved by treating with a reducing acid such as hydrochloric acid, sulfuric acid, phosphoric acid, or organic acid. Can be improved. In particular, acids such as hydrochloric acid, sulfuric acid and phosphoric acid are preferably used. By treating the metal surface with a reducing acid, the lubrication durability is further improved because the reactivity of the metal and the sulfur-containing compound is improved by removing the oxide on the metal surface. It is thought that.

The hydrophilic compound used in the present invention is characterized in that it has at least one functional group capable of reacting with the sulfur-containing compound in the molecule. As the hydrophilic polymer capable of reacting with the sulfur-containing compound, a compound having a functional group such as an acid anhydride group, a hydroxyl group, a carboxyl group, an amino group, an isocyanate group, or an epoxy group can be employed.
In addition, after converting the functional group introduced into the metal surface by reacting the sulfur compound with the metal surface into another type of functional group by reacting with another compound, the hydrophilic compound may be reacted.

As the hydrophilic compound in the present invention, various maleic anhydride copolymers, in particular, methyl vinyl ether-maleic anhydride copolymer or a modified product thereof, hyaluronic acid, and functional groups such as a hydroxyl group, a carboxyl group, and a glycidyl group are included. Various acrylic polymers copolymerized with acrylic monomers, polyethylene glycol and derivatives thereof, and the like can be suitably used, but are not limited thereto.

The most preferred hydrophilic compound in the present invention has a functional group that can be chemically bonded to the functional group introduced on the metal surface by the above-described method in the molecule, and further, by adding a crosslinking agent, Examples thereof include various maleic anhydride copolymers that can react with functional groups of the compound to form a crosslinked structure, in particular, methyl vinyl ether-maleic anhydride copolymers or modified products thereof. In particular, these hydrophilic polymers having an acid anhydride ring can be chemically immobilized on the metal surface via the sulfur compound, and an appropriate amount of crosslinking can be introduced using a crosslinking agent. Therefore, it is possible to manufacture various medical devices having very excellent lubrication durability. In addition, it is particularly preferably used since safety to the human body has been sufficiently confirmed.

In addition, as the crosslinking agent of the present invention, a diol, a polyol, a polyethylene glycol, a dithiol, a thioglycerol, an amino alcohol, a diamine, a polyamine, and the like are reactive with an acid anhydride ring and have two or more functional groups. Is preferably used.
The blending ratio of the crosslinking agent to the hydrophilic compound is in a weight ratio, which is in the range of 0.03 to 3.0 parts of the crosslinking agent with respect to 100 parts of the hydrophilic compound. A particularly preferred range is 0.05 to 1 part. Outside this range, the lubricity and lubrication durability are poor.
A method in which these hydrophilic compounds and a crosslinking agent are mixed in the above-described composition is prepared, and a method generally used, such as a method of immersing in this solution, a method of applying a solution, or a method of spraying a solution, is used. Can be used.

As the solvent used in the coating solution, a general-purpose organic solvent such as a ketone such as acetone or methyl ethyl ketone, or a mixed solvent thereof can be used. A coating solution is prepared by dissolving in these solvents at a concentration of 0.5 to 10% by weight, preferably 1 to 8% by weight.
After being immersed in the above coating solution, it is dried and subsequently subjected to a heat treatment at a temperature of 60 to 130 ° C. for 10 to 300 minutes. By this treatment, a crosslinked structure is introduced into the hydrophilic compound, and the lubrication durability is remarkably improved.

Furthermore, by immersing in an alkaline solution and converting the carboxyl group of the hydrophilic compound to an alkali salt, it is possible to produce a medical device having excellent lubricity and lubrication durability. As an alkali used for this alkali treatment, any alkali can be used as long as it can achieve the purpose of converting the carboxyl group into an alkali salt. From the viewpoint of lubrication durability, it is particularly treated with an alcohol solution of an alkali metal alkoxide. To give the best results.
After the alkali treatment, it is preferable to thoroughly remove the alkali by thoroughly washing with ethanol, water or the like.

Specific examples and comparative examples according to the present invention will be described in more detail below, but the present invention is not limited to the following examples.
(Synthesis of hydrophilic compounds)
10 g of methyl vinyl ether maleic anhydride copolymer <GANTREZ-AN169> manufactured by IPS was dissolved in 500 ml of methyl ethyl ketone (MEK) to obtain a coating solution <1>.
(Coating solution adjustment)
PEG200 as a cross-linking agent was added to the coating solution <1> so as to be 0.075% by weight with respect to GANTR-AN-169 to obtain a coating solution <2>.

<Example 1>
A metal core 2 for catheter guide wire having a diameter of 0.4 mm shown in FIG. 1 (center wire is NI-Ti alloy and coating is stainless steel) was ultrasonically cleaned in acetone and dried. Further, it was immersed in a 10% aqueous hydrochloric acid solution at 70 ° C. for 5 minutes and then thoroughly washed with water. Subsequently, it was treated with a 0.2% aqueous solution of triazine thiol monosodium salt for 10 minutes under a nitrogen stream, thoroughly washed with acetone, and left to dry at room temperature for several hours. As a result of analyzing the surface of the metal core 2 thus obtained by XPS, it was confirmed that sulfur and nitrogen were present, and triazinethiol was reactively immobilized on the surface of the metal core.

The metal core 2 was dipped in the coating solution <2> prepared above to apply the coating solution <2> to the surface of the metal core 2, air-dried, and then dried at 80 ° C. for 2 hours. Furthermore, the heat treatment at 125 ° C for 2 hours causes the acid anhydride group in the AN-169E molecule to react with the thiol group and crosslinker introduced on the surface of the metal substrate, and the lubricant is chemically applied to the surface of the metal core. To form a coating layer 4. After that, it was immersed in 1/1 N NaOH aqueous solution and treated at room temperature for 60 minutes. Furthermore, it was washed thoroughly with water and dried at 70 ° C for 30 minutes. The metal core 2 for the guide wire obtained by the above method showed excellent lubricity in water. In addition, by manually handling the guide wire made of the metal core 2 in water, the number of times of handling until the lubricity disappeared was measured. It was confirmed that the lubrication durability was excellent.

<Comparative Example 1>
The same metal core as the metal core 2 for the catheter guide wire used in the examples was used. After ultrasonically cleaning the metal core 2 in acetone, the metal core is immersed in the coating solution <1> prepared above to apply the coating solution <1> to the surface of the metal core, air-dried, and then at 80 ° C. Drying was performed for 2 hours. Furthermore, heat treatment was performed at 125 ° C for 2 hours, and then immersed in 1/10 N NaOH aqueous solution and treated at room temperature for 60 minutes. Furthermore, it was washed thoroughly with water and dried at 70 ° C for 30 minutes. When the metal core 2 was handled in water by hand, the number of times of handling until the lubricity disappeared was measured. However, the lubricity disappeared after 30 times, and the lubrication durability of the coating layer 4 was extremely inferior. It was.

The catheter guide wire of the present invention has a flexible distal end and can reliably reach the predetermined site in the body cavity. In addition, a coating layer in which a hydrophilic polymer having a crosslinked structure that has wettability when chemically wet is provided on the surface of the metal core and the coil spring body, so that sliding of the guide wire in the body cavity is smooth. Easy to insert into the neighborhood

It is sectional drawing of the longitudinal direction of the guide wire for catheters of this invention. FIG. 2 is a cross-sectional view of the distal end of the guide wire shown in FIG. FIG. 2 is a front end cross-sectional view showing a method of manufacturing the guide wire shown in FIG. It is a front end sectional view of the guide wire of the present invention which has a coil spring body. It is sectional drawing of the front end of the guide wire which shows the other example of a coil spring body.

Explanation of symbols

2: Metal core
4: Coating layer
6: Center wire
8: Coating material
10: Base end
12: Tip
14: Intermediate part
15: Coil spring body
16: First coil
17: Second coil

Claims (6)

A metal having a tip formed in a tapered shape, including a metal core composed of a center wire made of a metal having a low modulus of elasticity and a cover made of a metal having a high modulus of elasticity covering the center wire. A guide wire for a catheter, characterized in that a coating layer in which a hydrophilic polymer having a crosslinked structure wettable when wet is chemically bonded is provided on the surface of the core. A metal coil spring body is inserted through the tip of the tapered metal core, the rear end thereof is fixed to the coating material of the tip, and the tip is fixed to the tip of the tapered metal core. 2. The guide wire for a catheter according to claim 1, wherein The coil spring body is composed of a first coil and a second coil joined to the first coil and made of a material having a larger elastic modulus than the first coil, and the first coil is a tip portion of a metal core. 3. The catheter guide wire according to claim 1, wherein the guide wire is provided on a side. 4. The guide wire for a catheter according to claim 1, wherein the center wire is made of a superelastic alloy, and the covering is made of stainless steel or a copper alloy. 5. The catheter guide wire according to claim 1, wherein the hydrophilic polymer has a functional group capable of reacting with a sulfur compound in the molecule. 6. The catheter guide wire according to claim 1, wherein the hydrophilic polymer is a maleic anhydride copolymer having a crosslinked structure, or a modified product thereof.