JP2696053B2 - Medical device having lubricating surface, method for producing the same, and coating agent therefor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an improvement of a medical device such as a catheter requiring surface lubrication.

[0002]

2. Description of the Related Art With the improvement of medical device technology, medical devices having higher safety are required. In particular, catheters inserted into the respiratory tract, trachea, gastrointestinal tract, urethra, blood vessels and other body cavities or tissues, and various medical devices such as guidewires inserted into these may damage mucous membranes or cause inflammation during insertion. Excellent lubricity is required to avoid this. For this reason, various measures have been taken to reduce frictional resistance by applying silicone oil, olive oil, glycerin or the like to the surface of the tool, but this is not sufficient in terms of durability and storage. As a method for solving such a defect, a reactive functional group is introduced into the surface of the tool base material, and a water-soluble polymer or a derivative thereof is covalently or ionic-bonded through the functional group, thereby having high durability and excellent durability. A method of forming a lubricating coating has been proposed (JP-A-59-8134).
No. 1, Japanese Unexamined Patent Application Publication No. 1-195863, Japanese Patent Publication No. 1-3318
No. 1). This method is the most effective treatment method for obtaining a highly durable and excellent lubricating coating.However, the introduction of reactive functional groups requires complicated methods or long pretreatment depending on the type and properties of the substrate. When the substrate is a metal or ceramics, disadvantages such as the necessity of coating with a substrate into which a functional group can be introduced arise. On the other hand, a ship bottom antifouling paint (Japanese Unexamined Patent Publication No.
-97173, JP-A-61-11273) are known. However, in each case, a crosslinked structure is used as the water-soluble polymer. That is, these coating agents have a structure in which a crosslinked water-soluble polymer is dispersed and fixed as a powder in a urethane-based binder and are not suitable for delicate coating on medical devices.

[0003]

SUMMARY OF THE INVENTION It is an object of the present invention to apply directly to medical device substrates (including metals and ceramics) without performing complicated pretreatments such as introduction of reactive functional groups on the substrate surface. Accordingly, an object of the present invention is to provide a lubricating medical device having an excellent versatility, a high lubricating property, and a durable lubricating coating formed thereon, a process for producing the same, and a coating agent for the lubricating medical device.

[0004]

Means for Solving the Problems As a result of intensive studies, the present inventor has found that the above problems can be solved by adopting a specific coating agent, and has reached the present invention.

[0005] That is, the present invention provides (1) coating a coating material comprising a polyvinyl ether-maleic anhydride copolymer or a partial ester thereof, a silicone-containing fluoroacrylate polymer and an organic solvent on a substrate constituting a medical device. Then, a medical device having a lubricating surface obtained by alkali treatment, (2) a base material constituting the medical device, a polyvinyl ether-maleic anhydride copolymer or a partial ester thereof, a silicone-containing fluoroacrylate polymer and an organic A method for producing a medical device having a lubricating surface, which comprises applying a coating agent comprising a solvent and then treating with an alkali, (3) a polyvinyl ether-maleic anhydride copolymer or a partial ester thereof, and a silicone-containing fluoroacrylate. Providing lubricity for medical devices consisting of polymers and organic solvents Computing agent is one that its gist.

[0006] The coating agent used in the present invention comprises a silicone-containing fluoroacrylate polymer as a binder bonded to a medical surface substrate, a vinyl ether-maleic anhydride copolymer firmly fixed by the binder, and an organic compound. Consists of a solvent.

The silicone-containing fluoroacrylate polymer is a polymer having a silyl group that is hydrolyzed by moisture in the air, and can be bonded to various types of substrate surfaces by silane crosslinking. Has hydrophilic and hydrophobic microdomain structures and exhibits high blood resistance (Japanese Journal of Thoracic Surgery, 40 , 7, 72 (110). 1992), and also has a vinyl ether-maleic anhydride copolymer in it. It has the feature that it is fixed to. Such a silicone-containing fluoroacrylate polymer is a (meth)
Obtained by radical polymerization of acrylic acid ester, perfluoro (meth) acrylate, and optionally other polymerizable vinyl monomers such as styrene in the presence of alkoxysilanes such as methyltrimethoxysilane and γ-mercaptopropyltrimethoxysilane. be able to.
There are no particular restrictions on the proportions of these monomers and alkoxylanes.

[0008] The component for imparting lubricity to the medical device used in the coating agent of the present invention must be blendable with the above-mentioned binder component at an arbitrary ratio. It is preferable that the water-soluble component is substantially chain-like and has no cross-linked structure, and furthermore, in the present invention, a vinyl ether-maleic anhydride copolymer or a partial ester thereof is used from the viewpoint of lubricity when containing water, solubility in an organic solvent, etc. use. This copolymer has an average molecular weight of 1
About 100,000, preferably in a molar ratio of vinyl ether:
Maleic anhydride 1: 1. When used as a partial ester, the half ester type is preferred.

The organic solvent used in the coating agent of the present invention is not particularly limited as long as it is a solvent having excellent compatibility between both, and for example, methyl ethyl ketone, tetrahydrofuran, acetone and the like are suitable. If it is necessary to impart lubricity to the surface of the lubricating coating as a partial ester type of polyvinyl ether-maleic acid, it is possible to use a mixed solvent of methanol or ethanol and acetone 1: 1. These compatibilizers can polymer blend the silicone-containing fluoroacrylate polymer and the vinyl ether-maleic anhydride copolymer or a partial ester thereof in an arbitrary ratio, but have good durability and lubricity when wet. The ratio of the silicone-containing fluoroacrylate polymer as a binder to the polyvinyl ether-maleic anhydride copolymer or a partial ester thereof for imparting lubricity is important for imparting. When the weight ratio of the binder to the maleic anhydride copolymer exceeds 1: 1, lubricity is not exhibited. On the other hand, when the weight ratio of the maleic anhydride copolymer to the binder exceeds 9: 1, the lubricating property after formation is not improved. The disadvantage is that the coating elutes in water. Therefore, it is necessary that the coating agent of the present invention comprises the binder and the maleic anhydride copolymer or a partial ester thereof in a weight ratio of 1: 1 to 1: 9, particularly 1: 2 to 1: 3. It is preferable to set the degree. This coating agent can be coated on the substrate surface by dipping, spraying, sponge or the like, but the concentration at the time of coating is preferably about 1 to 10% in consideration of workability, coating method and the like. The subsequent drying step promotes a condensation reaction due to the formation of a siloxane bond by hydrolysis of a silyl group in the binder, and firmly fixes the maleic anhydride copolymer on the substrate surface.
It is necessary to carry out at 20 ° C. for 10 hours or more.

As a method of developing lubricity in the coating thus formed, it is usually necessary to immerse the maleic anhydride in water or to cleave the maleic anhydride by steaming. However, the coating with the coating agent of the present invention requires a binder. Exerts a strong effect, and lubricity is not exhibited by ordinary processing. In order to develop lubricity in the present invention, the formed coating is treated in an alkaline aqueous solution such as caustic soda, sodium carbonate, sodium hydrogen carbonate, and aqueous ammonia.
-100 ° C. for 5 minutes to 2 hours. Preferably, 20 to 30% by weight of caustic soda aqueous solution is used.
Perform immersion treatment at ６０60 ° C. for 0.5 to 1 hour. When coated as a partial ester type, 20 to 1 in an aqueous solution adjusted to about pH 7.5 to 9.0 with sodium bicarbonate.
00 ° C, 1-2 hours, preferably pH 8.0 ± 0.
2. Treat at a liquid temperature of 20 to 60 ° C for 1 to 1.5 hours. The coating after the alkali treatment is thoroughly washed in a water stream. It is also effective to perform cleaning for about 5 minutes using an ultrasonic cleaner as needed. Thereafter, drying is performed at room temperature to about 60 ° C. for 1 to 5 hours. A more lubricious coating can be formed. As described above, according to the present invention, a medical device having a lubricating surface can be formed in a short time. The medical device to which the present invention can be applied is a device such as a catheter or a guide wire which is inserted into a trachea, a digestive tract, a urethra, a blood vessel or other body cavities or tissues, and particularly requires surface lubrication. .

[0011]

The embodiments will be specifically described below. Production of Silicone-Containing Fluoroacrylate Polymer A method for producing the silicone-containing fluoroacrylate polymer (binder) used in the following examples will be described.

100 parts of toluene is placed in a kolben, and the mixture is heated with stirring and heated to 100 ° C., and 35 parts of methyl methacrylate, perfluoroalkyl (C6-C12) methacrylate (FAMAC-M, trade name, manufactured by NOK) 55
Parts, 20 parts of styrene and γ-mercaptopropyltrimethoxysilane (SH6062 manufactured by Dow Corning Toray)
A mixture of 7 parts, 3 parts of azobisisobutyronitrile and 5 parts of toluene was added dropwise over 2 hours, and the mixture was reacted at the same temperature for 2 hours. 1 part of azobisbutyronitrile
And reacted at the same temperature for 2 hours. The polymer thus obtained had 1648 cm ⁻¹ due to a fluorine-carbon double bond.
Has no infrared absorption spectrum and has a molecular weight of 1
It was 300.

Example 1 (Preparation of coating agent) Polyvinyl ether-maleic anhydride copolymer (trade name: GANTREZAN-139 MW41,000G)
To 4 g of AF (manufactured by AF Co.), 76 g of methyl ethyl ketone is added and dissolved by stirring. Next, the mixture is stirred for 10 to 15 minutes while gradually adding 20 g of the binder shown in the above-mentioned Production Example , and polymer-blended. When the maleic anhydride copolymer is used as a half-ester type, the dissolution of the polyvinyl ether-maleic anhydride half-ester copolymer is changed to methyl ethyl ketone, and a mixed solvent of 76 g of methyl or ethyl alcohol 1 to acetone 1 is used. Dissolve.

Example 2 (Formation of lubricating coating) Using a Ni-Ti core wire having an outer diameter of 0.45 mm, a polyurethane resin (trade name: Pelesen, manufactured by Dow Chemical Co.) was extruded on the core wire to form an outer diameter of 0.4 mm. 85mm x 1500m length
m guide wire was prepared. The coating agent shown in Example 1 was applied to the surface of this guide wire,
Dried for 15 hours. Subsequently, it was immersed in a 0.4% aqueous solution of caustic soda for 1 hour at room temperature to exhibit lubricity. After washing 6
The sample was dried at 0 ° C. × 5 hours to obtain a sample (1). The sample (1) was subjected to a slip property and a repetition test described later. The results were good.

Example 3 The coating agent of the half ester type (methyl ester) shown in Example 1 was applied to the guide wire shown in Example 2 and dried at 100 ° C. for 15 hours. Subsequently, pH 8.0
In a sodium bicarbonate aqueous solution adjusted to ± 0.1.
It was immersed for 5 hours to develop lubricity. After washing with an ultrasonic cleaner for 5 minutes, the sample was dried at 60 ° C. × 3 hours to obtain a sample (2). Sample (2) was tested for slipperiness and repetition as described below. The results were good.

Example 4 The guide wire shown in Example 2 was immersed in tetrahydrofuran for several seconds and dried at room temperature. Thereafter, PVC was dissolved in tetrahydrofuran to prepare a 5% PVC / THF solution. A guide wire was immersed in this solution, dried at 60 ° C. for 5 hours, and the surface of the guide wire was coated with PVC. The coating agent shown in Example 1 was applied to this guide wire and dried at 100 ° C. for 15 hours. Subsequently, it was immersed in a 0.4% aqueous solution of caustic soda for 1 hour at room temperature to exhibit lubricity. After washing with water and drying at 60 ° C. × 5 hours, a sample (3) was obtained. Sample (3) was tested for slipperiness and repetition as described below. The results were good.

Example 5 A Ni-Ti core wire having an outer diameter of 0.45 mm was used, and a nylon elastomer (trade name: manufactured by Pebax Toray Co., Ltd.) was extruded from the core wire to obtain an outer diameter of 0.85 mm × length of 1500 m.
m guide wire was prepared. The coating agent shown in Example 1 was applied to the surface of this guide wire,
Dried for 15 hours. Subsequently, it was immersed in a 0.4% aqueous solution of caustic soda for 1 hour at room temperature to exhibit lubricity. After washing 6
The sample was dried at 0 ° C. × 5 hours to obtain a sample (4). Sample (4) was tested for slipperiness and repetition as described below. The results were good.

Comparative Example 1 A 5% polyvinyl ether-maleic anhydride copolymer (trade name GANTREZ) was added to the guide wire shown in Example 2.
AN-139 GAF) methyl ethyl ketone solution was prepared and applied. After drying at 60 ° C. for 2 hours, steam treatment was performed at 60 ° C. for 1 hour to cleave maleic anhydride to develop lubricity. After washing with water and drying at 60 ° C. for 5 hours, a sample (5) was obtained. Sample (5) was tested for slipperiness and repetition as described below. As a result, the initial frictional resistance was as good as those of the samples (1) to (4) coated with the present coating agent, but it was found that the durability was extremely poor in the repeated test.

Reference Example The guide wire shown in Example 2 was immersed in tetrahydrofuran for several seconds and dried at room temperature. Thereafter, PVC was dissolved in tetrahydrofuran to prepare a 5% PVC / THF solution. 5% of 4,4'-diphenylmethane diisocyanate was dissolved in this solution, a catheter was immersed in this solution to introduce a functional group, and dried at room temperature. Furthermore, monoethyl ester of polyvinyl ether-maleic anhydride (trade name GA
NTREZ, SP-215 MW60,000 GAF
5% methyl ethyl ketone solution at 60 ° C
X 2 hours. Subsequently, the sample was immersed in water for 1 hour and dried at room temperature for 10 hours to obtain a sample (6). For the sample (6), the results of the slipperiness and the repetition test described later were good.

Slipperiness and Repetition Test A hard polyethylene tube having an outer diameter of 2.9 mm, an inner diameter of 2.3 mm, and a length of 500 mm was filled with a U-shaped tube having a central portion bent to have a radius of curvature of 13 mm with purified water. Insert the entire length of the guide wire from the
The resistance at that time was pulled up at a speed of "in", and the resistance at that time was measured with a balance (using a 500 g spring balance). Guide wire is repeatedly U
Measure the increase in load by inserting the tube into the tube (load measurement was performed for each of 1, 2, 5, 10, 20, 50, and 100 times of insertion for convenience). Was replaced for each load measurement. Regarding the durability of the coating, the life until the rise when the load suddenly increased with the number of repeated insertions was defined as the life. Table 1 below shows the test results performed in the examples and the comparative examples.

[0021]

[Table 1]

[0022]

As described above, the lubricating coating with the coating agent according to the present invention does not require any pretreatment such as introduction of a functional group on the surface of various medical device base materials as shown in Table 1. It is possible to form a lubricating coating which imparts slipperiness and durability and can be practically used sufficiently.
This effect is at least as high as the case where a functional group is introduced into the surface of the base material and then further coated as shown in the reference example.

Claims (3)

(57) [Claims] 1. A coating material comprising a polyvinyl ether-maleic anhydride copolymer or a partial ester thereof, a silicone-containing fluoroacrylate polymer and an organic solvent is applied to a base material constituting a medical device, followed by alkali treatment. Medical device having a lubricating surface. 2. A base material constituting a medical device is coated with a coating agent comprising a polyvinyl ether-maleic anhydride copolymer or a partial ester thereof, a silicone-containing fluoroacrylate polymer and an organic solvent, and then subjected to an alkali treatment. A method for producing a medical device having a lubricating surface, characterized by comprising: 3. A lubricating coating agent for medical devices comprising a polyvinyl ether-maleic anhydride copolymer or a partial ester thereof, a silicone-containing fluoroacrylate polymer and an organic solvent.