JPH0160126B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a contact lens that can be worn continuously, and more particularly to a contact lens that is highly safe, requires no care, and is disposable.

The contact lenses of the present invention can be used in exactly the same way as conventional contact lenses.

[Technical background and explanation of conventional technology]

Contact lenses are spectacle lenses that are worn directly on the cornea of the eyeball, and are broadly divided into soft contact lenses that can absorb moisture and hard contact lenses that can hardly absorb moisture. Epithelial cells often die if they are not constantly supplied with oxygen dissolved in tears, so contact lenses are highly water-containing,
Soft contact lenses that are hydrophilic and allow water to easily diffuse are said to be preferred.

Recently, high water content soft contact lenses made of synthetic polymer materials have been commercially available, but synthetic polymer materials are foreign to the cornea of living organisms.
It's hard to say it's ideal. The cornea is primarily composed of collagen and mucopolysaccharides, and contact lenses made from collagen are said to be biocompatible. (Patent No. 101619, Japanese Unexamined Patent Publication No. 1983)
Contact lenses made of chitin and chitosan were also developed (Japanese Patent Application Laid-open No. 56-94322).
Regarding materials, a composite material of chitosan and collagen (Japanese Patent Application Laid-open No. 183344/1982) and a composite material of N-acyl chitosan and collagen (Japanese Patent Application No. 93868/1982) have been developed.

Collagen is a component of the cornea and has a high water content, so it does not damage corneal epithelial cells and is most suitable as a material for contact lenses that can be worn continuously. However, collagen is a protein and has a high water content. However, it is easily degraded by proteolytic enzymes such as collagenase, which poses problems for long-term use. On the other hand, chitin and chitosan are natural polymers, but because they do not exist in mammals, they have problems in that they have poorer biocompatibility than collagen in humans, who are mammals, and are brittle and inflexible. However, chitin and chitosan also have the advantage that they are cheaper than collagen, more stable against proteolytic enzymes, and easier to process. Therefore, if collagen is mixed with chitin and chitosan, a contact lens with excellent flexibility can be obtained, but it has not yet reached a stage where it can be said to be sufficient in terms of biocompatibility for humans.

The present inventors are continuing research on chitosan and collagen, and in their research, N-
It was discovered that a composite material of acyl chitosan and collagen has excellent biocompatibility with the cornea of the human eye, and based on this finding, the present invention was achieved.

[Object of the invention and summary of the invention]

An object of the present invention is to provide a contact lens that has excellent biocompatibility and can be worn continuously. Specifically, it is an object of the present invention to provide a contact lens that has excellent biocompatibility and can be worn continuously. Our goal is to provide the following.

The present invention is a contact lens made of a mixture of N-acyl chitosan and collagen.

The contact lens of the present invention is manufactured by molding a mixture of N-acyl chitosan and collagen in a lens mold. To mold a mixture of N-acyl chitosan and collagen, an acylating agent is added to a mixed solution of chitosan and collagen.
This can be carried out by placing the mixed solution in a contact lens mold before the gelation reaction is completed, and gelling the mixed solution within the mold. A molded product of the mixture can be crosslinked, thereby making it possible to mold a contact lens with high dimensional stability.

The N-acyl chitosan in the contact lens of the present invention can be acylated with a saturated or unsaturated fatty acid having 1 to 32 carbon atoms or a dicarboxylic acid having 2 to 8 carbon atoms. The collagen mixture contains hyaluronic acid, chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, polymethyl methacrylate, hydroxyethyl methacrylate, silicone, cellulose acetate butyrate, siloxanyl methacrylate, polyvinylpyrrolidone and polyvinyl alcohol. The contact lens may contain an additive selected from the group consisting of the following, thereby improving the biocompatibility and in-vivo stability of the contact lens.

The crosslinking treatment of the contact lens molded product in the present invention can be carried out by a crosslinking reaction of a mixture of N-acyl chitosan and collagen using a polyepoxy compound, or by irradiation with radiation such as gamma rays or ultraviolet rays.

[Specific description of the invention]

As the N-acyl chitosan in the contact lens of the present invention, any type of N-acyl chitosan can be used as long as the biocompatibility of the contact lens is not lost.
Contact lenses with excellent biocompatibility can be obtained by using acylated with anhydrides of about 10 saturated fatty acids. The acylation rate of N-acyl chitosan may be any value as long as it does not impair the biocompatibility of the contact lens, but an acylation rate of 60 to 80% is preferable.

Collagen in the contact lens of the present invention is a rod-shaped molecule with a molecular weight of about 300,000, but any collagen can be used as long as it has been extracted and purified from living organisms. It is preferable to use soluble collagen and atelocollagen extracted with pepsin, and it is particularly preferable to use atelocollagen with low antigenicity. It is also possible to use chemically modified collagens (eg, acylated or esterified), but it is preferable to use succinylated collagen.

In the contact lens of the present invention, collagen accounts for 0.1 to 50% (by weight) of the weight of the contact lens.
, but preferably in an amount of 10 to 30% (by weight) of the weight of the contact lens.

The crosslinking treatment in the contact lens of the present invention can be carried out by either chemical crosslinking treatment using a crosslinking agent or crosslinking treatment by irradiation with radiation or ultraviolet rays, but in the crosslinking treatment using gamma rays, mainly collagen is Since chitosan may partially decompose due to crosslinking and gelation, the crosslinking treatment in the contact lens of the present invention is preferably performed by crosslinking with a chemical agent (crosslinking agent), and a polyepoxy compound is used as the chemical agent. It is preferable to do so. Such chemical agents include polyethylene glycol diglycidyl ether, polyglycerol polyglycidyl ether and sorbitol polyglycidyl ether.

The crosslinking treatment can be carried out by directly adding a polyepoxy compound to the mixture of N-acyl chitosan and collagen, but it is also possible to form a mixture of collagen called N-acyl chitosan into a contact lens.
It is preferable to immerse the molded article in a solution of a polyepoxy compound.

The contact lens of the present invention can contain a mucopolysaccharide such as hyaluronic acid or a synthetic polymeric substance such as polyvinyl alcohol. These mucopolysaccharides and synthetic polymer substances are added to the mixture of N-acyl chitosan and collagen before contact lens molding, but the amount added should be 10% or less of the total weight of the contact lens. preferable.

By including these mucopolysaccharides,
By improving the biocompatibility of contact lenses and incorporating synthetic polymeric substances, the stability of contact lenses in vivo, that is, preventing decomposition by enzymes, thereby improving the stability of their shape. Can be done.

The mold used for molding the contact lens of the present invention is a mold that is separated into upper and lower parts, consisting of a concave lower mold and a convex upper mold, and the concave surface of the lower mold contains chitosan, collagen, and acylating agent. A convex upper mold is fitted on top of the mixed solution, and in the cavity formed between the upper mold and the lower mold,
This mixed solution is gelled to produce a molded contact lens. A heating device can be attached to the contact lens mold to promote gelation of this liquid mixture through an acylation reaction. The molded contact lens is taken out from the mold, and burrs on the periphery are removed to produce a manufactured contact lens.

Hereinafter, the present invention will be explained in more detail by showing an example of implementation, but the present invention is not limited to these examples.

Example 1 0.8 g of commercially available atelocollagen was dissolved in 0.6 1NHCl and 160 ml of water, and the solution was sterilized by filtration using a membrane filter (pore size: 0.45 μm). 0.6 ml of 1N NaOH was added to the filtrate, and the mixture was centrifuged at 10,000 G to collect the precipitate. A 2% aqueous acetic acid solution was added to this precipitate to make the total volume 50 ml, and the precipitate was well dissolved.

Separately, 3 g of commercially available chitosan (degree of deacetylation: 100%) was dissolved in 50 ml of a 2% acetic acid aqueous solution.
The solution was placed in an autoclave and autoclaved at 120°C for 15 minutes. After cooling to room temperature, add the atelocollagen solution described above, mix well, and add 100 ml of ethanol.
Mixed well.

2 ml of acetic anhydride was added to this mixed solution and stirred quickly. Within 1 minute, the mixed solution was poured into the concave lower mold of a lens mold, and the convex upper mold was placed on top of it. The molded product in the lens mold turned into a gel after 30 minutes. Remove the molded product from the lens mold,
After washing this with physiological saline for 72 hours, the burr on the periphery of the lens molding was cut off using a cylindrical cutter to obtain a contact lens having a tapered circumference of the present invention.

All of the above manufacturing steps were performed aseptically.

The acetylation rate of all amino groups in chitosan and atelocollagen in this contact lens is
It was 90%.

Example 2 0.8 g of commercially available atelocollagen (extracted from calf dermis with pepsin) was added to a 2% aqueous acetic acid solution at 50%
ml to prepare an acetic acid aqueous solution of atelocollagen.

Commercially available chitosan (degree of deacetylation: 100%) 3
Dissolve g in 50 ml of 2% acetic acid aqueous solution, add the entire amount of atelocollagen acetic acid aqueous solution prepared above, mix well, and add 100 ml of methanol to this.
was added and mixed well. Add acetic anhydride to this mixture.
1.33 g was added, stirred quickly, and within 1 minute, the mixed solution was poured into a lens-shaped concave lower mold, and a convex upper mold was placed on top of it. The molded product in the mold had become a gel after 30 minutes.

Separately, add 0.1M sodium carbonate aqueous solution to 10g of polyglycerol polyglycidyl ether.
Add 40 ml and 50 ml of ethanol and dissolve well to prepare a polyglycerol polyglycidyl ether solution.The molded product taken out from the lens mold was immersed in this and reacted at 30°C for 4 hours.
Crosslinking was introduced into the molded product.

The molded product was lifted from the polyglycerol polyglycidyl ether solution, immersed in running water, washed with water for 24 hours, and then transferred to physiological saline.
This was sterilized by irradiation with 2.5M rad gamma rays, and the burrs on its periphery were cut off using a cylindrical cutter to produce the tapered circumference contact lens of the present invention.

60% of amino groups in this contact lens
was acetylated with acetic anhydride, and the remaining 40% of the amino groups were crosslinked with polyglycerol polyglycidyl ether. These amino groups are the total amount of amino groups of chitosan and atelocollagen.

Example 3 Add 100 ml of methanol to 100 ml of mixed acetic acid solution of chitosan and atelocollagen obtained in the same manner as Example 2.
was added and mixed well. 2.8 g of hexanoic anhydride was added to this mixed solution, stirred quickly, and then poured into a concave lens-shaped lower mold within 1 minute.
- Obtained contact lenses made of hexanoyl collagen.

The hexanoylation rate of amino groups in this contact lens was 60%.

Example 4 5 g of commercially available N-succinylated chitosan (succinylation rate: 90%) and 2 g of commercially available succinylated collagen (succinylation rate: 95%) were dissolved in 100 ml of physiological saline (PH: 7.5), and N- A succinylated chitosan-succinylated collagen solution was prepared.

Separately, a hyaluronic acid solution was prepared by dissolving 0.1 g of hyaluronic acid in 50 ml of physiological saline.
Also, add 0.6 g of polyvinyl alcohol to 50 g of physiological saline.
ml to prepare a polyvinyl alcohol solution.

This hyaluronic acid solution and polyvinyl alcohol solution are mixed into the N-succinylated chitosan-succinylated collagen solution obtained above,
Prepare 200ml of a mixed solution, pour this mixed solution into a concave lower mold of a lens shape, cover it with a convex upper mold and pressurize it. ) to gel the mixture inside the lens mold. The gelled molded product was removed from the lens mold and finished with a cylindrical cutter to obtain a contact lens of N-succinylated chitosan-succinylated collagen-hyaluronic acid-polyvinyl alcohol.

〔Effect of the invention〕

The contact lens of the present invention has excellent strength characteristics, high affinity with the cornea, and no side effects even when worn for two weeks or more.

Claims (1)

[Claims] 1. A contact lens comprising a mixture of N-acyl chitosan and collagen. 2. The contact lens according to claim 1, wherein the mixture of N-acyl chitosan and collagen is crosslinked. 3. Claim 1 or 2, wherein the N-acyl chitosan is acylated with a saturated or unsaturated fatty acid having 1 to 32 carbon atoms or a dicarboxylic acid having 2 to 8 carbon atoms. Contact lenses as described in section. 4 A mixture of N-acyl chitosan and collagen contains hyaluronic acid, chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, polymethyl methacrylate, hydroxyethyl methacrylate, silicone, cellulose acetate butyrate, siloxanyl methacrylate The contact lens according to any one of claims 1 to 3, characterized in that the contact lens contains a lens selected from the group consisting of polyvinylpyrrolidone, polyvinyl pyrrolidone, and polyvinyl alcohol. 5. A method for producing a contact lens, which comprises molding a mixture of N-acyl chitosan and collagen. 6.For molding of the mixture of N-acyl chitosan and collagen, an acylating agent is mixed into a solution of the mixture of chitosan and collagen, and before the gelation is completed, the mixed solution is poured into a contact lens mold and molded. 6. The method of manufacturing a contact lens according to claim 5, wherein the method is carried out by gelling and molding in a mold. 7. The method for producing a contact lens according to claim 5 or 6, wherein the molded product of the mixture of N-acyl chitosan and collagen is crosslinked. 8. The acylating agent according to any one of claims 5 to 7, wherein the acylating agent is a saturated or unsaturated fatty acid having 1 to 32 carbon atoms or a dicarboxylic acid having 2 to 8 carbon atoms. How to make contact lenses. 9 A mixture of N-acyl chitosan and collagen contains hyaluronic acid, chondroitin, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, polymethyl methacrylate, hydroxyethyl methacrylate, silicone, cellulose acetate butyrate, siloxanyl methacrylate 9. The method for manufacturing a contact lens according to any one of claims 5 to 8, characterized in that the contact lens comprises a contact lens selected from the group consisting of polyvinylpyrrolidone, polyvinylpyrrolidone, and polypinyl alcohol. 10. The method for producing a contact lens according to any one of claims 6 to 9, wherein the crosslinking treatment of the molded product is performed using a polyepoxy compound. 11. The contact lens according to any one of claims 7 to 10, wherein the crosslinking treatment of the molded product is performed by irradiating the molded contact lens with gamma rays or ultraviolet rays. production method.