JPH05309131A - Surface improved medical tool improved by surface polymerization - Google Patents

Abstract

PURPOSE:To provide a surface-improved layer excellent in surface lubricity and biocompatibility in a medical tool by previouly providing a high molecular compound having a radical polymerization starting group in its principal chain to the surface of the base material, so that the radically polymerizable monomer is polymerized on the surface of the material. CONSTITUTION:A medical tool such as a catheter requires surface lubricity for facilitating the insertion into a blood vessel or tissue and for preventing the tissue from being injured, and also requires biocompatibility. Therefore, a high molecular compound having a radical polymerization starting group in its principal chain is provided to the surface of the base material of the medical tool, and after low-temperature plasma has been irradiated or at the time of irradiation, a radically polymerizable monomer is supplied in the gaseous phase for polymerizing it on the surface of the material. Thereby, a surface improved layer including a copolymer of a hydrophilic polymer and a compositional polymer, or a surface improved layer including a copolymer in which water-soluble high molecular chain have been made insoluble is formed.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a material surface-modified by surface polymerization, and more particularly to a medical device having a material surface having excellent surface lubricity and biocompatibility.

[0002]

2. Description of the Related Art As a method for forming a surface modified layer containing a block or graft copolymer, a method of coating the block or graft copolymer is generally used. For example, Journal of biomedical materials
Reseaech. Vol.20., 919-927 (1986), an excellent blood compatibility is obtained by coating a block copolymer composed of a hydrophilic polymer chain and a hydrophobic polymer chain on the surface of a substrate. It is described to create a surface with properties. However, in this method, since the solvent in which the block copolymer is dissolved is limited, the substrates that can be coated are also limited. For example, it has been difficult to coat on a base material that is easily deteriorated by the solvent or a base material having poor wettability (a solvent having a large contact nucleus with the solvent).

As a method of forming a surface-modified layer by surface polymerization, a method of generating radicals capable of initiating polymerization by using plasma, ozone, electron beam, γ-ray and the like and surface graft polymerization is disclosed. (JP-A-2-263)
845, JP-A-59-152913, USP44078.
46, USP 3826678). However, since these do not allow a polymer compound having a polymerization initiation group in the main chain to exist on the material surface, radicals capable of initiating polymerization are limited to radicals generated on a substrate, etc., and as a result,
The amount of radicals produced and radical stability differed depending on the substrate, and there were many materials that were difficult to undergo graft polymerization.
For example, a material that is easily dehydrogenated such as hydrogen bonded to a tertiary carbon such as polypropylene is likely to undergo surface graft polymerization, and a polymer material that is difficult to dehydrogenate such as polyphenylene sulfide, polystyrene, or nylon, stainless steel or It was difficult to graft-polymerize metals such as aluminum and ceramics. In addition, depending on the substrate, high-power plasma or long-time plasma prepolymerization, etc., which is surface-graft-polymerized, is required, so that in thin materials or materials with special shapes, deformation or minute cracks may occur, There was a problem in practical use.

Japanese Unexamined Patent Publication (Kokai) No. 2-229839 describes a method of separately supplying two kinds of monomers by a plasma surface graft polymerization method to form a surface modified layer containing a block copolymer. Also in this method, since the amount of radicals produced and the radical stability differ depending on the substrate, there have been materials that are difficult to undergo graft polymerization.

Conventionally, as a surface modification method using a polymer compound having a polymerization initiation group or a prepolymer,
In general, a polymer compound having a polymerization initiating group such as an azide group, an azo group or a peroxide group in the side chain of a monomer is coated on the material surface as a photosensitive polymer and photocured by UV or the like. (For example, "Photosensitive polymer" from Kodansha Scientific, Functional Polymer Series), the photosensitive polymer is pre-existed on the surface of the substrate, and then contacted with a monomer gas. Processes such as post-polymerization have not been investigated. In particular, for the purpose of creating a surface of a medical material, formation of a surface-modified layer containing a block copolymer using a polymer compound having a polymerization initiation group in the main chain has not been studied.

On the other hand, a polymer compound having a polymerization initiating group in the main chain is a polymer peroxide (Polymer, vol.
2, p19-28 [1991]) and macroazo compounds (collection of polymer articles, vol.47, No.4, 321-329 [1990),
It is used in the synthesis of block copolymers. Block copolymers synthesized by using polymeric peroxides are used for surface modification of polymer materials as a solvent coating method, but due to restrictions of solvents and base materials,
There was a limit to the application to medical materials with special shapes and functions.

[0007]

Therefore, an object of the present invention is to provide a material or medical material in which a surface-modified layer containing a block copolymer having excellent surface lubricity and biocompatibility is firmly and uniformly formed. To provide tools.

[0008]

[Means for Solving the Problems] A polymer compound having a radical polymerization initiation group in the main chain is present in advance on the surface of a substrate,
This is achieved by a material surface-modified by polymerizing a radically polymerizable monomer on the material surface.

The present invention also shows a surface-modified material characterized in that a radically polymerizable monomer is supplied in a gas phase after the irradiation with low temperature plasma or at the time of irradiation to polymerize the material surface. Is. The present invention is further a surface-modified material characterized in that a surface-modified layer containing a copolymer of a hydrophilic polymer and a hydrophobic polymer is formed by surface polymerization. It shows a surface-modified material characterized in that a surface-modified layer containing a copolymer in which a water-soluble polymer chain is insolubilized is formed by polymerization.

The present invention will be described in detail below. The polymer compound having a radical polymerization initiation group in the main chain of the present invention (polymerization initiator) has a radical polymerization initiation group represented by an azo group, a peroxide group, a disulfide group, etc. in the main chain. It is a polymer polymerization initiator. The polymerization initiation group present in the main chain of the polymer chain is decomposed by heat, light (ultraviolet rays, vacuum ultraviolet rays, lasers, etc.), plasma, electron beams, reducing substances (redox type), etc. Then, the block copolymer is produced by polymerizing the monomer using the radical as a polymerization initiation point. When no polymerizable monomer is present, a surface-modified layer is formed by a crosslinking reaction due to a reaction between radicals or a graft reaction due to a reaction with a substrate.

A blending method or a coating method can be considered as a method for allowing a polymer compound having a radical polymerization initiating group in the main chain to be present on the surface of the material in advance. Preferably, a large amount can be retained on the surface. G method. The material used as the base material is not particularly limited, such as polymer materials, ceramics, and metals.

The high molecular weight polymerization initiator has an average molecular weight of 5,000 or more, preferably 10,000 or more.
When the molecular weight is small and the number of polymerization initiating groups present in the molecule is large, the chain length of the polymer forming the polymer polymerization initiator becomes short, so that the expected effect, for example, the adhesive effect with the base material, the phase This is because the separation effect, the elution prevention effect, etc. cannot be sufficiently exhibited.

Examples of the polymerizable monomer used in the present invention include acrylic, methacrylic, acrylamide and vinyl monomers having an unsaturated bond capable of radical polymerization.

According to the surface polymerization method of the present invention, the block copolymer is formed on the surface of the substrate as described above. In addition to the block copolymer, a homopolymer, a graft copolymer or a crosslinked product thereof. , Additives, fillers, etc. may be present on the surface.

The surface polymerization needs to be carried out under the condition that the polymer polymerization initiator is not eluted. Preferred is a method of polymerizing the monomer supplied in the gas phase on the surface of the base material. Since no solvent is used, the method has excellent operability and is a clean method.
For example, in an atmosphere from which oxygen is removed, heating, light irradiation (ultraviolet rays, vacuum ultraviolet rays, lasers, etc.), plasma irradiation, electron beam irradiation, etc. cleaves the polymer polymerization initiator to generate radicals. The monomer can be supplied and polymerized under reduced pressure. The method of initiating the polymerization by the plasma treatment is preferable because it can be surface-modified by a series of vacuum processes until the completion of the polymerization because of excellent operability. The plasma treatment is a method of treating a material surface by utilizing a discharge phenomenon called “low temperature plasma” or “non-equilibrium plasma”. 10
A high-frequency electric field, a microwave electric field, or a direct-current electric field is applied to a low-pressure gas of 0 mmHg or less to generate low-temperature plasma, and this plasma gas flow, plasma atmosphere, or active species or vacuum ultraviolet light generated by plasma is brought into contact with the material surface. This is a method of performing surface treatment by

According to the production method of the present invention, the block copolymer is synthesized on the material surface as described above.
As a material used in contact with living tissue such as a medical device or blood, it is preferable to include a block copolymer composed of a hydrophilic or hydrophobic polymer. It is generally known that in the case of a hydrophobic polymer, platelet adhesion to activation, and in the case of a polymer exhibiting high hydrophilicity, long-term contact with blood in vivo shortens the platelet life. In the case of a hydrophilic-hydrophobic block copolymer, it is possible to improve blood compatibility by forming an appropriate hydrophilic surface and forming an appropriate phase separation structure.

Further, making the surface of the material hydrophilic makes it possible to improve the wearing sensation by improving the wettability with a body fluid, for example, in the case of a contact lens, or the material and cells or tissues such as a bioimplant material. By improving the adhesiveness of the above, the bacterial infection is reduced, and the added value is added to the medical device. Generally, it is difficult to coat a hydrophilic polymer uniformly on a hydrophobic polymer material because the hydrophilic polymer has poor compatibility with the hydrophobic polymer. However, according to the method of the present invention, the hydrophilic polymer has a high hydrophobicity. By surface-polymerizing a hydrophilic monomer with a molecular polymerization initiator, it becomes possible to easily form a hydrophilic surface.

Further, in medical devices such as catheters, it is desirable to impart surface lubricity so that they can be easily inserted into blood vessels and tissues without damaging the tissues. As a method of imparting surface lubricity, a method of insolubilizing a water-soluble polymer to form a water-absorbent gel layer on the material surface is excellent.
According to the method of the present invention, by forming a material surface containing a copolymer of a water-soluble polymer and a water-insoluble polymer,
It is possible to easily provide a medical device having surface lubricity. The water-absorbent gelling layer is a surface that absorbs water and gels, and can be prepared by holding a water-soluble polymer on the surface. As the water-soluble polymer, a water-soluble polymer or cellulose containing (meth) acrylic acid, a (meth) acrylic monomer, an acrylamide monomer, a maleic acid monomer or the like as a main constituent component. Preferable examples include polysaccharides such as derivatives.

The present invention is characterized in that it is a medical device used in contact with body fluids and tissues of living organisms, but alkoxyalkyl acrylates such as methoxyethyl acrylate, which are less irritating to living tissues. It is preferable that a surface-modified layer containing a polymer mainly composed of pearls is formed.
Medical devices include film-shaped, thread-shaped, tube-shaped, etc.
The shape and use of the porous material are not particularly limited.
Tells (cate-tel, balloon Cat-tel, balloon,
Preferable examples include catheter guide wires and the like), wound dressing materials, artificial blood vessels, storage containers for blood and body fluids, medical devices to be implanted in a living body (port portion, etc.), and the like.

[0020]

EXAMPLES The present invention will be described in more detail below with reference to examples.

Examples 1 to 5 Oligoesters obtained by dropping 29.7 g of triethylene glycol into 72.3 g of adipic acid dichloride at 50 ° C. and then removing hydrochloric acid under reduced pressure at 50 ° C. for 3 hours. 22.5g
Methyl ethyl ketone (4.5 g) was added to the solution, and the mixture was added dropwise to a solution consisting of 5 g of sodium hydroxide, 6.93 g of 31% hydrogen peroxide, 0.44 g of surfactant dioctyl phosphate and 120 g of water, and reacted at -5 ° C for 20 minutes. Let The obtained product was repeatedly washed with water and washed with methanol and then dried to obtain a polycondensed polymer-ATPPO having a plurality of peroxide groups in the molecule. Subsequently, 0.5 g of methoxyethyl acrylate (ME
A) 9.5 g, DMF 30 g as a solvent were mixed, and the temperature was 65 ° C.
After polymerizing under reduced pressure for 24 hours, it was reprecipitated with diethyl ether to obtain PMEA having a peroxide group in the molecule.

The PMEA thus obtained was added to 0.5
As a wt% methanol solution, a sheet of polystyrene, polyethylene, polyethylene terephthalate, polyphenylene sulphite, nylon 610 was coated. Each coated sheet was irradiated with a plasma in argon at 0.2 Torr for 50 W for 10 seconds, and then N, N-dimethylacrylamide (DMAA) was supplied in a gaseous state,
Surface polymerization was performed at 0.8 Torr for 3 minutes. After the surface polymerization, the sample was heated at 60 ° C. for 1 hour under reduced pressure and then washed with water to obtain a sample.

When any of the sheets was immersed in water, the surface swelled to gel and the lubricity was increased. This is
These surface-modified materials do not physically affect the tissue.
It suggests reducing the dizziness.

Comparative Examples 1 to 5 DMAA was surface-polymerized in the same manner as in Examples 1 to 5 except that PMEA having a peroxide group in the molecule was not coated. The surface lubricity of the obtained sheet was low, and there was a clear difference as compared with Examples 1-5.

Example 6, Comparative Example 6 0.5 g of ATTPO as a polymerization initiator, 9.5 g of methyl methacrylate (MMA), and 30 g of DMF as a solvent.
Were mixed and polymerized under reduced pressure at 65 ° C. for 24 hours and then reprecipitated with diethyl ether to obtain PMMA having a peroxide group in the molecule. PMMA obtained in this way
As a 0.5 wt% methanol solution was coated on an acrylic sheet containing PMMA as a main component. Coat the acrylic sheet to 50 at 0.2 Torr in argon.
After irradiating the plasma for 10 seconds with W, methoxyethyl acrylate (MEA) was supplied in a gaseous state to 0.8 Torr.
r Surface polymerization was carried out for 3 minutes. 60 after surface polymerization
After heating under reduced pressure at 1 ° C for 1 hour, the sample was washed with methanol to obtain a sample. (Example 6)

In order to examine the blood compatibility of the acrylic sheet surface-polymerized with methoxyethyl acrylate, the number of adherent platelets after contacting with platelet-rich plasma for 30 minutes was examined. Almost no platelets adhered to the surface. On the other hand, many platelets adhered to the acrylic sheet (Comparative Example 6) used as the base material.

[0027]

INDUSTRIAL APPLICABILITY According to the present invention, a polymer compound having a radical polymerization initiating group in the main chain is preliminarily present on the surface of a base material, and a radically polymerizable monomer is polymerized on the surface of the material to achieve excellent surface lubrication. It is possible to provide a material or medical device in which a surface-modified layer containing a block copolymer having properties and biocompatibility is firmly and uniformly formed.

Further, after or at the time of irradiation with low-temperature plasma, a radically polymerizable monomer is supplied in a gas phase to polymerize on the material surface, and further, by surface polymerization, the copolymerization of hydrophilic polymer and hydrophobic polymer is carried out. A more suitable material or medical device can be provided by forming a surface modification layer containing a coalesce or a surface modification layer containing a copolymer in which a water-soluble polymer chain is insolubilized.

Claims (1)

[Claims] 1. A surface-modified material, characterized in that a polymer compound having a radical polymerization initiating group in the main chain is previously present on the surface of a base material, and a radically polymerizable monomer is polymerized on the material surface. ..