JPH04202441A - Medical tool having surface lubricity when wet and preparation thereof - Google Patents

Abstract

PURPOSE:To improve wet lubricity by combining reactive groups introduced to the surface of a substrate material constituting a medical tool with a water- swellable polymer. CONSTITUTION:A substrate material constituting a medical tool (e.g. a catheter) is irradiated with a low-temp. plasma under a reduced pressure of 0.001-100Torr or in an atmosphere of N2 or air for 0.5-60sec, and to the surface of the material is supplied a compd. having a reactive functional group (e.g. acrylic acid) in a gas phase in the absence of plasma to graft the compd. onto the surface, thus introducing the reactive functional groups to the surface. Then, the material is dipped in a soln. contg. a water-swellable polymer (e.g. a maleic anhydride polymer having an average mol.wt. of 3-5 million) to react with the polymer, i.e., to combine the reactive groups with the polymer.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a medical device and a method for manufacturing the same. More specifically, the present invention relates to a medical device that has excellent lubricity when wet due to a polymer bonded to a base material, and a method for manufacturing the same.

(Prior art) Base material surfaces of medical devices such as catheters inserted into the trachea, gastrointestinal tract, urethra, blood vessels, and other body cavities or tissues, as well as medical devices such as guide wires and stylets inserted into these. In general, thrombotic properties, tissue adhesion, tissue damage, and foreign body reactions are observed. For this reason, these medical devices need to be smooth enough to avoid damaging tissues and allow for reliable insertion to the target site, and they also need to be smooth enough to avoid damaging mucous membranes due to friction while indwelling within tissues. It is required to exhibit excellent lubricity to avoid burning or causing irritation.

For this reason, low-friction materials are used as the base material, and the surface of the base material is further coated with a hydrophilic polymer.

For example, low-friction materials such as fluororesin and polyethylene resin are used as base materials for these medical devices, and fluororesin, silicone oil, olive oil, glycerin, and the like are further coated on the surfaces of these devices.

However, these methods cannot be expected to provide permanent lubricity, and there are safety problems such as detachment, peeling, and elution of lubricating substances from the surface of the base material. For example, when using low-friction materials such as high-density polyethylene or applying surface coatings using them, there are problems such as the coefficient of friction not being sufficiently low.Furthermore, when applying oil to the surface, the coefficient of kinetic friction is low. However, the effect is not long-lasting, and the oil etc. may run off or the surface becomes sticky, making it difficult to store as a product, so it is necessary to apply it immediately before use, making it complicated to handle. There is a problem.

Further, US Pat. No. 4,100,309 discloses the use of a copolymer of polyvinylpyrrolidone and polyurethane as a material that provides lubricity. In this method, in terms of lubricity and durability, it is essential to use a method that can be graded I, or to use two or more types of polymers that can be coated, and the presence of incyanate groups as reactive groups. Therefore, it is impossible and undesirable for the isocyanate group to react with a base material having low reactivity and a polymer having lubricating properties.

In addition, JP-A No. 59-81,341 discloses that unreacted isocyanate groups are generated on the surface of a medical device, and this surface is treated with a hydrophilic copolymer that covalently bonds with the isocyanate groups to impart lubricity. The method is disclosed. By this method, good lubricity can be obtained on the surface of the base material, and the lubricity can be expected to last to some extent. but,
In this method, when the hydrophilic copolymer is mainly composed of N-vinyl-2-pyrrolidone, etc., the film strength of the polymer is not sufficient, and the film is damaged by repeated friction, making it difficult to maintain sufficient durability. There is a problem with not being able to do it.

Furthermore, in Japanese Patent Publication No. 1-55,023, a compound having an active hydrogen having a main chain of a copolymer of two or more types of monomers is bonded to the surface of a medical device via a polyisocyanate compound. A method of imparting compatibility is disclosed.

However, in this method, the presence of at least one of amino groups, imino groups, carboxyl groups, and mercapto groups on the surface of the base material constituting the medical device is essential;
Medical devices that do not have the above-mentioned functional groups, such as polyolefins and halogenated polyolefins, have the disadvantage that they cannot be treated.

Furthermore, Japanese Patent Publication No. 1-33,181 discloses that by covalently bonding a reactive functional group present on the surface of a base material constituting a medical device with a maleic anhydride-based polymer substance, the base material becomes wet when wet. A method of imparting lubricity to a surface is disclosed. However, this method also requires the presence of a reactive functional group on the surface of the base material constituting the medical device, and has the drawback that it cannot be directly introduced into a base material that does not have a reactive functional group. In addition, when using a base material that does not have a reactive functional group, there is a method in which the reactive functional group is caused to exist on the surface of the base material by treating the base material in advance with a solution of a compound that converts the reactive functional group into H. As described in the above-mentioned publication, there is a problem in that unless the compound is stably bonded to the surface of the substrate, the water-swellable polymer cannot be stably bonded.

(Problem to be Solved by the Invention) Therefore, the present invention is not limited to the material of the base material, and furthermore, the present invention provides a permanent low-temperature solution in body fluids such as saliva, digestive juices, and blood, and in aqueous solvents such as physiological saline and water. The object of the present invention is to provide a medical device that has frictional properties and is highly safe, and a method for manufacturing the same.

(Means for Solving the Problems) The above objects are to introduce at least one reactive functional group into at least a part of the surface of a base material constituting a medical device by a plasma-initiated graft polymerization method; This is achieved by a medical device that exhibits lubricity when wet, which is characterized by combining this functional group with a water-swellable polymer.

The present invention also provides a medical drinking device in which the medical device is a catheter. The present invention also provides a medical device in which the water-swellable polymer is a polysaccharide.

The present invention further provides a method of introducing at least one reactive functional group into the surface of at least a portion of the base material constituting the medical device by plasma-initiated raft polymerization, and combining this functional group with a water-swellable polymer. This is achieved by a method for manufacturing a medical device that exhibits lubricity when wet, which is characterized by combining the following.

(Function) The medical device according to the present invention that exhibits lubricity when wet has at least a portion of the surface of the base material constituting the medical device.
It is characterized in that at least one reactive functional group is introduced by a plasma-initiated craft polymerization method, and this functional group is bonded to a water-swellable polymer.

Compounds with these functional groups introduced onto the surface of the substrate include hydroxyl groups, thiol groups, amino groups, imino groups, carboxyl groups, carbamate groups, isocyanate groups, epoxy groups, and acid halokene groups. Specific examples include acrylic acid, methacrylic acid, glutaric acid, pimelic acid, allyl alcohol, ethyleneimine, glycidyl (meth)acrylate, (meth)acrylic acid chloride, and (meth)acryloyloxy. Examples include ethyl isocyanate. In addition, two or more types of compounds having these functional groups may be introduced, and at least either before or after introduction, esterification, amidation, sulfonation, oxidation, hydrolysis, quaternization, After chemical crosslinking is performed at least once to convert them into hydroxyl groups, thiol groups, amino groups, imino groups, carboxyl groups, carbamate groups, isocyanate groups, epoxy groups, and acid halogen groups, water-swellable polymers are formed. You can also combine it with

In addition, water-swellable polymers that bind to these functional groups are polymers that swell or dissolve by absorbing water, and are suitable for use in body fluids such as saliva, digestive fluids, and blood, and in aqueous solvents such as physiological saline and water. It is not particularly limited as long as it has low friction properties, and specific examples include maleic anhydride-based polymer substances and polysaccharides. The maleic anhydride-based polymer substance may be a homopolymer or a copolymer of maleic anhydride, and in particular, a methyl vinyl ether-maleic anhydride copolymer is preferably used. Such as G, A, F, Corporation to G
Almost 1:1 commercially available as ANTREZ AN
Examples include copolymers of In addition, derivatives of maleic anhydride-based polymeric substances are not limited to those that are water-soluble; if the above-mentioned maleic anhydride-based polymeric substance is used as a basic composition, even insolubilized derivatives have a degree of freedom in their molecular chains, and Any material containing water may be used. Specifically, esterified products, salts, amidated products obtained by condensation, addition, substitution, oxidation, reduction reactions, etc. of the maleic anhydride-based polymer substances,
Anhydride, halide, ether compound, hydrolyzate, acetal compound, formal compound, alkyl compound, 4
graded products, diazotized products, hydrazidized products, sulfonated products,
Nitride, ionic complex, and reactive functional groups such as diazonium group, azide group, isocyanate group, acid chloride group, acid anhydride group, iminocarbonate group, amino group, carboxyl group, epoxy group, hydroxyl group, aldehyde group, etc. Examples include crosslinked products with substances that contain two or more , and copolymers with vinyl compounds, acrylic acid, methacrylic acid, diene compounds, etc. Among these, partial alkyl esters are particularly preferred. Such a maleic anhydride-based polymer substance dissolves well in water, and by treating it with the solution, frictional resistance can be significantly reduced, and a base material with excellent lubricity can be obtained.

In addition, lubricity can be similarly obtained with derivatives obtained by condensation, addition, or substitution reactions of these maleic anhydride-based polymeric substances, and with so-called insolubilized products that have been partially crosslinked. . Further, the average molecular weight of the maleic anhydride-based polymer used in the present invention is not particularly limited, but one of about 3 to 5 million has high lubricity, has an appropriate thickness, and has a high degree of swelling when hydrated. This is preferable because a lubricating layer that is not extremely large can be obtained.

Examples of polysaccharides that can be used as water-swellable polymers include hyaluronic acid, chondroitin, chondroitin sulfate, keratan sulfate, keratan polysulfate, heparanic acid, and their salts, which are widespread in animal tissues and body fluids. Examples include certain mucopolysaccharides and alginic acid and its salts, which are commonly ingested by humans.These polysaccharides are expected to be highly safe when used in medical devices.
preferable.

Furthermore, in order to bond these functional groups to a water-swellable polymer, it is preferable to bond them via a compound having reactive groups at both ends, such as a diamine, diisocyanate, or jepoxy group.

Further, in the present invention, a plasma initiated polymerization method is used as a method for introducing the compound having a reactive functional group -F into the surface of the substrate. - Methods for introducing such compounds onto the surface of the substrate for boat fishing include hydrogen abstraction agents, neutron beam irradiation, gamma ray irradiation, electron beam irradiation, plasma irradiation, etc. to generate radicals on the substrate surface. Methods using neutron beam irradiation, gamma ray irradiation, and electron beam irradiation are known, but methods using neutron beam irradiation, gamma ray irradiation, and electron beam irradiation are not preferred because they generate radicals on the surface of the substrate and even inside the substrate, which may impair the physical properties of the substrate. Therefore, in the present invention, a plasma-initiated polymerization method is used, which is an application of a method using plasma irradiation that can generate radicals only on the surface.

In order to introduce the above-mentioned reactive functional group onto the surface of the substrate by plasma-initiated polymerization, it is carried out under a reduced pressure of 0.001 to 100 Torr, preferably 0.01 to 10 Torr, in an atmosphere of argon, nitrogen, air, various monomers, etc. After irradiating with low-temperature plasma for 0.5 to 60 seconds, preferably 1 to 30 seconds, the graft polymerization is carried out by supplying the compound having the functional group in the absence of plasma.

It is not necessary to directly bond compounds with these reactive functional groups to the radicals generated on the surface of the base material, and in order to maintain the physical properties of the base material, it is necessary to use a compound with a low glass transition point such as ethyl acrylate. After bonding the conjugate, the hydroxyl group,
Thiol group, amino group, imino group, carboxyl group,
A compound having a carbamate group, an isocyanate group, an epoxy group, or an acid halogen group may be introduced onto the surface of the base material.

Further, the shape of the medical device of the present invention may be a flat membrane, a hollow fiber, a solid fiber, a sheet, a tube, a nonwoven fabric, a woven fabric, or a composite thereof. In particular, a so-called catheter, which has a tube shape that can be inserted into a blood vessel or other body cavity or tissue, is preferable.

Examples of the form of the medical device of the present invention include membranes for artificial kidneys, membranes for plasma separation, catheters, membranes for artificial lungs, artificial blood vessels, anti-adhesion membranes, artificial skin, wound dressing materials, materials for implants, etc. I can do it. In particular, it is suitably used as a catheter inserted into a blood vessel or other body cavity or into a tissue.

Furthermore, the base material constituting the medical device used in the present invention may vary depending on the intended medical device, such as polyolefin, halogenated polyolefin, polyether, polyester, polyurethane, polyimine,
Examples include polyimide, nylon, polymers containing tertiary carbon, and mixtures thereof. In particular, polyolefins, halogenated polyolefins, polyurethanes, or mixtures thereof are preferred in view of operational considerations.

The medical device of the present invention has a water-soluble or water-swellable polymer chemically firmly introduced onto the surface of the base material. Therefore, in the medical device of the present invention, platelet adhesion, which is a factor in thrombus formation, is not observed on the surface of the base material, unlike when conventional polyolefin, halogenated polyolefin, or polyurethane is used as a low-friction base material. , can be in contact with blood for a long time. Furthermore, with the medical device of the present invention, the phenomena of detachment, peeling, and elution of the coating agent from the surface of the substrate, which are observed in methods of applying silicone oil, olive oil, glycerin, etc., to the surface of the substrate, are not observed.
High safety is ensured.

As described above, the medical device of the present invention permanently exhibits platelet suppressing action and low friction in body fluids and aqueous solvents, and furthermore, ensures excellent safety.

(Example) Hereinafter, the present invention will be explained more specifically using examples.

However, the material of the base material used in the present invention may be one type or two or more types as long as it is as described above, and the shape of the base material may be a single shape or a combination of those materials as long as it is as described above. It may also have a composite shape.

Examples 1 to 3 Polypropylene sheet (manufactured by Futamura Chemical Co., Ltd., FOP#
Low temperature plasma (Ar, 1
Torr) for 10 seconds, the compounds (monomers) shown in Table 1 were supplied in the gas phase, and surface craft polymerization was carried out at a temperature of 288°C.

The sheet was washed with a good solvent for one day, dried, and
, 4-diaminobutane in 5% acetone solution at 40°C, 6
Allowed time to react.

After drying, incubate at 40° in a 2% maleic anhydride acetone solution.
A sample having lubricity was obtained by reacting for C11 hours.

Further, as a continuous indicator of lubricity, the sheet thus obtained was extracted with a good solvent at 70° C. for 30 minutes, and the UV of the extract was measured.

The results are shown in Table 1.

Comparative Examples 1-3 Sheets similar to Examples 1-3 were soaked in a 2% solution of the polymer for 5 minutes without plasma-initiated graft polymerization.
Coating was carried out at 5°C.

Thereafter, the sheet was treated in the same manner as in Examples 1 to 3 to obtain 1.4-
Treatments with diaminobutane solution and maleic anhydride solution were carried out sequentially.

Similarly, as a continuous indicator of lubricity, extraction was performed at 70° C. for 30 minutes using a good solvent for the polymer, and the UV of the extract was measured.

The results are shown in Table 1.

Examples 4 to 6 Platelet adhesion tests were conducted on sheets similar to those in Examples 1 to 3. After contacting a fresh human surface with a sheet (1 cm x 1 cm) for 5 minutes, it was fixed using cultaraldehyde.
After dehydration, the number of platelets adhesion was measured using a scanning electron microscope at 300x magnification.

The results are shown in Table 2.

Comparative Examples 4 to 6 Platelet adhesion tests were conducted on sheets similar to those in Comparative Examples 1 to 3 using the same method as in Examples 4 to 6.

The results are shown in Table 2.

(Effects of the Invention) As described above, the present invention introduces at least one reactive functional group onto the surface of at least a portion of a base material constituting a medical device by a plasma-initiated graft polymerization method. It is a medical device that has surface lubricity when wet, and is characterized by combining a group with a water-swellable polymer.
The medical device of the present invention has a water-soluble or water-swellable polymer chemically firmly introduced onto the surface of the base material.

Therefore, in the medical device of the present invention, platelet adhesion, which is a factor in thrombus formation, is not observed on the surface of the base material, unlike when conventional polyolefins, halogenated polyolefins, and polyurethanes are used as low-friction base materials. Can be brought into prolonged contact with blood.

Furthermore, the medical device of the present invention does not exhibit the phenomenon of detachment, peeling, or elution of the coating agent from the surface of the substrate, which is observed in methods of applying licorice oil, olive oil, glycerin, etc. to the surface of the substrate, and is highly safe. gender is ensured.

In addition, the medical device of the present invention has extremely low frictional resistance on the surface of the medical device, especially when wet with body fluids such as saliva, digestive juices, and blood, or aqueous liquids such as physiological saline and water, that is, in a wet state. Frictional resistance becomes extremely small, which provides advantages such as ease of insertion, alleviation of patient pain, and prevention of damage to mucous membranes and vascular intima.

Furthermore, the present invention introduces functional groups by generating radicals on the surface of the base material by plasma irradiation, and there are almost no restrictions on the base materials to which it can be applied, so it can be used for various medical devices and has versatility. Excellent.

Claims (4)

[Claims] (1) At least one reactive functional group is introduced onto the surface of at least a portion of the base material constituting the medical device by a plasma-initiated graft polymerization method, and this functional group is bonded to a water-swellable polymer. A medical device that exhibits lubricity when wetted. (2) The medical device according to claim 1, wherein the medical device is a catheter. (3) The medical device according to claim 1 or 2, wherein the water-swellable polymer is a polysaccharide. (4) At least one reactive functional group is introduced onto the surface of at least a portion of the base material constituting the medical device by a plasma-initiated graft polymerization method, and this functional group is bonded to a water-swellable polymer. A method for manufacturing a medical device that exhibits lubricity when wet, characterized by: