JPS6022926A - Hydrogel - Google Patents

Abstract

PURPOSE:To obtain the hydrogel having excellent adaptability to a living body by polymerizing (copolymerizing) a monomer and/or a plymer of alpha-methylene-N- alkyl lactam expressed by the formula with a polymerizable vinyl monomer and/or a polymer. CONSTITUTION:The hydrogel is a polymerization (copolymerization) product of (A) a monomer and/or a polymer of alpha-methylene-N-alkyl lactam expressed by the formula (n is 1-3 integer, and R is a C1-C6 alkyl group) and (B) a polymerizable vinyl monomer and/or a polymer. And the ratio of the component (A) is regulated to >=20wt% of the total amt. of the component (A) and the component (B). The hydrogel thus obtained is provided with excellent adaptability to a living body and also with excellent mechanical properties. The hydrogel is preferably used for soft contact lenses, catheters, culture medium of cells, blood flow circuits, embedding materials of enzyme and medicine, and various kinds of separation membranes.

Description

DETAILED DESCRIPTION OF THE INVENTION [Technical Field] The present invention relates to a novel hydrogel that is insoluble in water and highly hydrophilic, and is mainly used as a medical amulet.

[Prior art]

In recent years, the application of polymeric materials to the medical field has been actively studied. Among them, hydrogels that are insoluble in water and highly hydrophilic are classified as 9. , substances (gases, ions, molecules, etc.)
It has attracted attention for its permeability and water content, and its functions similar to those of the human body.It has been used in various separation membranes, catheters, knotted contact lenses, blood storage containers, cell culture substrates, blood flow circuits, enzymes, and pharmaceuticals. It has come to be used for embedding and abduction, etc.

For this purpose, hydrogels using hydrophilic monomers such as 2-hydroxynibble methacrylate, (meth)acrylic acid, (meth)acrylamide, and N-vinylpyrrolidone have been used so far. 1 For example, N-
Hydrogels using N-vinyl lactams such as vinylpyrrolidone.

It is described in JP-A-55+74049, etc.

However, when trying to increase the permeability of these hydrogels, their mechanical strength suddenly decreases or their transparency is lost, and their mechanical strength is not as strong as originally thought.
It has become clear that they have problems such as poor compatibility with living tissues, blood, and body fluids.

[Purpose of the invention]

The object of the present invention is to have excellent compatibility with living organisms and excellent mechanical properties. The purpose of the present invention is to provide a new hydrogel.

[Structure of the invention]

The present invention (However, nwl, 2 or 3. R is c, -C.

α-methylene, -N-alkyl lactam monomers and/or polymers containing B, other monomers capable of vinyl polymerization and/or polymers thereof; A (co)polymerization product comprising: 1. The proportion of A component.

The hydrogel is characterized in that the amount of both components A and B is 20% by weight or more based on the total amount.

The α-methylene-N-alkyl lactam monomer of component A is a component that imparts hydrophilicity to the hydrogel of the present invention, such as 1-methyl-3-methylene-2-pyrrolidinone (α-methylene-N- Methylpyrrolid: / @ n 筺1 + R-CH3) H1-inpropyl-3-methylene-2-piperidone (nz2゜2-oxohexahydroazepine ("-3+ R=CHs), etc. Methods for producing these compounds is publicly known, for example, J, Org,
Chem, 19. P893-902 (1974) and
J, Org, Chew, 42. P1180-11
85 (1977). These monomers can be used alone or in combination of two or more.

Further, the α-methylene-N-alkyl lactam polymer is as follows.

(1) Single or copolymer of α-methylene-N-alkyl lactam (2) A (co)polymer having a polymerizable double bond in the molecule synthesized from α-methylene-H-alkyl lactam. This polymer is 1 e.g. 1-methyl-5-methylene-2
It can be obtained by copolymerizing -pyrrolidinone and 2-hydroxyethyl methacrylate and reacting it with (meth)acrylic acid chloride.

These monomers and polymers may be used alone or as a mixture. As component A of the present invention, 1-methyl-3-methylene-2-pyrrolidinone and a polymer synthesized from this monomer having a polymerizable double bond in the molecule can be preferably used.

The vinyl polymerizable monomer and its polymer as component B are:
It is as follows.

(1) Hydrophilic monomers polyethylene glycol mono(meth)acrylate, alkoxypolyethylene glycol mono(meth)acrylate, N-vinyl lactams such as N-vinylpyrrolidone and N-vinylpiperidone, (meth)acrylic acid, (meth)acrylic Hydroxyalkyl (meth)acrylates such as hydroxyethyl molybdenyl esters of acids.

One or more types of (meth)acrylamide, glycerin mono(meth)acrylate, etc.

(2) A single or copolymer of the above-mentioned hydrophilic monomers (3) A polymer having a polymerizable double bond in the molecule synthesized from the above-mentioned monomers. This polymer can be obtained, for example, by reacting a polymer of 2-hydroxyethyl methacrylate with methacrylic acid μlide.

(4) Hydrophobic monomer A monomer that provides a polymer that is insoluble or non-swellable in water when polymerized, and is an unsaturated nitrile such as (meth)acrylic acid alkyl ester or (meth)acrylonitrile. , aromatic olefins such as methylene, and vinyl compounds such as vinyl chloride and vinyl acetate.

(5) The above hydrophobic monomer alone or in combination (6)
A hydrophobic polymer having a polymerizable double bond in the molecule synthesized from the above hydrophobic monomer. for example.

A polymer obtained by copolymerizing (meth)acrylic acid alkyl ester or (meth)acrylonitrile with 2-hydroxyethyl methacrylate or glycidyl methacrylate, for example, is reacted with (meth)acrylic acid chloride or (meth)acrylic acid. Polymers with polymerizable double bonds in their side chains obtained by Examples include polymers having a polymerizable double bond at the end.

(7) A monomer having two or more polymerizable double bonds in the crosslinking agent molecule, which includes ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, Polyethylene glycol di(meth)acrylate, hexamethylene bis! Reimido.

Di- or trivinyl compounds such as divinylbenzene, N,N'-methylenebisacrylamide, trimethylolprobant, and (meth)acrylate.

These include allyl compounds such as diallyl succinate, diethylene glycol bisallyl carbonate, and triallylisocyanurate 1, allyl vinyl compounds such as allyl (meth)acrylate, and vinyl (meth)acrylate.

These B components are selected depending on the physical properties (water content, mechanical properties, material permeability, etc.) required of the hydrogel. For example, when high mechanical strength is required, it is desirable to use a hydrophobic intermediate that provides a polymer with a high glass transition temperature or a hydrophobic polymer with a high glass transition temperature. This B component may be a single monomer or polymer of the above (1) to (71), or a mixture thereof.In the present invention, as the B component, a hydrophobic monomer or polymer may be used. A hydrophobic polymer having a polymerizable double bond in the molecule synthesized from polymers and hydrophobic monomers, pre-crosslinking Q can be preferably used, but among them, (meth)ac 1-noric acid alkyl ester A polymer having a double bond in the molecule synthesized therefrom is preferably used.

It is necessary that the amount of component A is at least 20% by weight relative to the total amount of both components A and B. If the amount of damage caused by component A is less than 20, the moisture content will become too low.

It is well known that the material permeability of hydrogels varies greatly depending on the water content, and when the water content is low, the material permeability becomes worse. For example, Encyclopedi
a Of PO17mer 5science andT
technology, 5upp1. Voxl, p 1
95-219゜Enterescience Public
Shera (1976) states that the oxygen permeability coefficient of human logel decreases as the water content decreases/J% 2 For example, 25
In the case of °C, if the moisture content is changed from 60% to 50% and then to 40%, the value of the oxygen permeability coefficient will be 3
15.215 force; described. Therefore, in terms of compatibility with living organisms, etc., it is undesirable for the water content to become too low.

Copolymerization of component A and component B in such a ratio is as follows.

It is carried out by means of heat, light, radiation, etc., such as solution layer polymerization and bulk polymerization. Once the hydrogel of the present invention has an appropriate hardness when dried, it can be subjected to bulk polymerization to obtain a rod-shaped polymer, which can then be processed into a desired shape, or it can be formed into a molded product at the same time as the polymerization. The method of obtaining the same can also be applied. Examples of methods for molding simultaneously with polymerization include 1, for example, injecting raw materials into a mold and polymerizing and forming, 9, carrying out polymerization in a rotary mold, and applying it to a rod, etc., and pulling out the rod, etc. after one polymerization is completed.

Also, if a polymerization initiator is required during double polymerization.

Penzoyl peroxide, di-t-butyl peroxide, 2,4-dichlorobenzoyl peroxide, t
-Organic peroxides like butyl hydroperoxide, ammonium persulfate, azo compounds like azobisisobutyronitrile, azobiscyclohexanecarbonitrile, azobisdimedelvaleronitrile etc. 9 For the production of conventional hydrogels 1j can be used before starting the polymerization.

Furthermore, the solvent used when solution polymerization is carried out is A
Dimethyl sulfoxide, N-methyl-2-pyrrolidone, N,N-dimethylacetamide, N, etc. may be used as long as they dissolve component B well to give a transparent stock solution and do not inhibit monopolymerization.

N-dimethylformamide, tetrahydrofuran.

1,4-dioxane and the like are preferably used.

After the polymerization is completed, the obtained copolymer is immersed in pure water or physiological saline to extract unreacted monomers and solvent, and is subjected to water conservation treatment to become a human gel.

〔Effect of the invention〕

The hydrogel obtained by the present invention has excellent first-order properties.

(1) Since it contains highly hydrophilic α-methylene-N-alkyllactam, it has excellent substance permeability and affinity with living organisms.

(2) α-methylene-N-alkyl lactams, which are different from N-vinyl lactams, have a low copolymerizability with hydrophobic monomers such as (meth)acrylic acid esters, so they are hydrophobic. By selectively using monomers and hydrophobic polymers that have polymerizable double bonds in 9 molecules, mechanical properties such as breaking strength and breaking elongation can be freely changed even if the water content is the same. That is, if a hydrophobic lit polymer is used, a hydrogel with excellent elongation at break can be obtained, and if a curvaceous hydrophobic polymer is used, a hydrogel with excellent breaking strength can be obtained.

(3) Since it has good copolymerizability with hydrophilic monomers such as Al'(L/n' glycol mono(meth)acrylate and (meth)acrylamide), a hydrogel with a uniform water-utilizing structure can be obtained.

[1 (J Application)] The hydrogel of the present invention can be used as soft contact lenses, catheters, substrates for cell culture, blood flow circuits, and embedding materials for enzymes, pharmaceuticals, etc. by taking advantage of the above-mentioned properties.

It can be preferably used for various separation membranes.

The present invention will be described in detail below with reference to Examples.

In the examples, 1 part represents part by weight.

Example 1 50 parts of methyl methacrylate, 50 parts of 1-methyl-3-methylene-2-pyrrolidinone (σ-methylene-N-methylpyrrolidone), 095 parts of triethylene glycol dimethacrylate, and 028 parts of azobisdimethylvaleronitrile were mixed with dimethyl A transparent stock solution was obtained by dissolving in 1222 parts of sulfoxide. Apply this stock solution to a sealing film (
(Product name: Sealon film manufactured by Fuji Photo Film Co., Ltd.) After pouring the spacer between two glass plates and fixing it with a fastener, the film was placed in an electric furnace and heated from 40°C to 90°C over 16 hours. Polymerization was carried out by increasing the After polymerization, the obtained solvent-containing film was removed from the glass plate, immersed in pure water, heated, and cooled.

A hydrogel film was obtained by repeating the liquid exchange six times.

The moisture content of the obtained film was 54%.

Also, the breaking strength is 29ζ/am”) and the breaking elongation is 415.
It was particularly excellent in elongation at break and was flexible.

Further, the transparency was also good.

Example 2 100 parts of methyl methacrylate, 1 part of 2- and droxyethyl methacrylate, 0 parts of azobisdimethylvaleronitrile
．． 05 parts were dissolved in 150 parts of 1,4-dioxane, and polymerization was carried out in a nitrogen stream at 50°C for 8 hours and then at 80°C for 2 hours. After the resulting solution was cooled, it was reacted with a large excess of methacrylic acid chloride using pyridine as a catalyst. This solution was poured into methanol solution to precipitate 9 polymers having polymerizable double bonds in their side chains, and then dried.

This polymer has a polymerizable double bond in its side chain.

Polymerization and post-treatment were carried out in the same manner as in Example 1, except that methyl methacrylate in Example 1 was replaced with 590 parts of dimethyl sulfoxide, and 122.2 parts of dimethyl sulfoxide was used to obtain a hydrogel film. The water content was 53%, and the breaking strength was about 40ζ/-1, and the breaking elongation was about 1 oov, which was superior to Example 1.

Example 3 40 parts of methyl methacrylate, 60 parts of methyl acrylate,
1 part of 2-hydroxyethyl methacrylate, 0.67 parts of azobisisobutyronitrile, and 5 parts of dimethyl sulfoxide.
67 parts, and polymerization was carried out at 70°0 for 8 hours in a nitrogen stream. After the polymerization was completed, the solution was poured into a methanol/water mixture to recover the polymer and remove the remaining monomers. After drying.

This polymer was dissolved in 1,4-dioxane, reacted with a large excess of methacrylic acid chloride in the presence of pyridine, and then poured into a methanol/water mixture.

A polymer having a polymerizable double bond in its side chain is recovered.

Dry.

30 parts of the above polymer having a polymerizable double bond in the side chain +
50 parts of 1-methyl-3-methylene-2-pyrrolidinone,
After 5 parts of azobisdimethylvaleronitrile 03' was dissolved in 186.7 parts of dimethyl sulfoxide to obtain a transparent stock solution, polymerization and post-treatment were carried out in the same manner as in Example 1 to obtain a transparent hydrogel film. The moisture content of the obtained film was 71%, despite the high moisture content.
Breaking strength is 25kg/2. The elongation at break was 160 cm:C, and the break strength was particularly excellent. .

Example 4 62 parts of a polymer having a polymerizable double bond in the side chain prepared in the same manner as in Example 3, 1-methyl-3-methylene-2
- 37.5 parts of pyrrolidinone, 57 parts of N-vinylpyrrolidone
．． 5 parts, vinyl methacrylate 0.3 parts.

0.54 parts of azobisdimethylvaleronitrile was dissolved in 361.6 parts of dimethyl sulfoxide to obtain a transparent stock solution. Polymerization and post-treatment were carried out in the same manner as in Example 1 to obtain a transparent hydrogel film. The moisture content is 73%, and the breaking strength is 221 parts g/cm2. The elongation at break is 1.60%, with good mechanical properties of 5! showed K.

Comparative Example 1 N was used instead of 1-methyl-3-methylene-2-pyrrolidinone (α-methylene-N-methylpyrrolidone) in Example 1.
- except that vinylpyrrolidone was used.

A hydrogel film was prepared in the same manner as in Example 1, but only a cloudy film with poor transparency was obtained.

Comparative Example 2 N-viny lupyrrolidone was used in place of 1-methyl-3-methylene-2-pyrrolidinone in Example 1.

Furthermore, triethylene glycol dimethacrylate 0.95
Example 1 was carried out in the same manner as in Example 1, except that 0.47 parts of triallylisocyanuride, which has good copolymerizability with N-vinylpyrrolidone, and 0.48 parts of triethylene glycol dimethacrylate were used instead of When a hydrogel film was created, a transparent film was obtained. The water content was 55%, but unlike the film obtained in Example 1, it was extremely rigid, and its mechanical properties were significantly different from those of living tissue, so it lacked compatibility with living organisms. there were.

Patent applicant Higashi Shikikai Co., Ltd.

Claims (1)

[Scope of Claims] α-methylene N-argyllactam monomer and/or moshike polymer prepared by (nx1* 2 or 3. R is a C, to C4 alkyl group) and B, vinyl A (co)polymerization product with a polymerizable monomer and/or its polymer, in which the proportion of component A is: A hydrogel comprising 20% by weight or more of the total amount of both components A and B.