JPH01297070A - Lens for refractive keratoplasty - Google Patents

Abstract

PURPOSE:To assure transparency, to improve optical properties and to eliminate inflammation reaction by using the lens for refractive keratoplasty which is constituted of soluble collagen and has about 70-90% moisture content. CONSTITUTION:This lens is the lens for refractive keratoplasty attached on the surface of the cornea layer or within the cornea layer. Said lens for refractive keratoplasty has about 70-90% moisture content and the balance is constituted essentially of the soluble collagen. For example, 10% transparent collagen gel is obtd. by dissolving the collagen into an acidic soln. of about pH3. This gel is put into the recess of a forming mold made of plastic and is defoamed under a reduced pressure to press the projecting part of the forming mold to the collagen gel. After the entire part of the mold is filled with nitrogen, the gel is irradiated with cobalt 60 for 2 hours, by which a crosslinking reaction is effected. The total irradiation dose of the cobalt 60 is specified to 1 megarad. The collagen lens obtd. in such a manner is swollen by a buffer soln. of phosphoric acid and is transferred into a physiological salt soln. where the lens is preserved. This collagen lens has about 70-90% moisture content and is optically transparent and highly soft.

Description

[Detailed description of the invention] [Industrial application field]

The present invention provides a refracticle I.
This is about Plasti River Lens.

[Background of the invention]

It is well known that contact lenses have been used as a means of correcting vision. This contact lens is made of polymethyl methacrylate.
1. So-called hard contact lens materials such as acrylic modified silicone resins, so-called soft contact lens materials such as hydrous resins such as poly-2-hydroxyethyl methacrylate and polyvinylpyrrolidone;
It is also made of other soft materials such as silicone rubber. However, some patients cannot wear such contact lenses, and contact lenses are not absolute. Additionally, corneal transplant surgery is also performed in some areas. However, corneas are difficult to handle, cannot be stored for long periods of time, and there is no perfect disinfection method for corneas, and the corneas cannot be used safely due to immune biological reactions. There are drawbacks. In addition, instead of using the removed cornea, the above-mentioned contact lens! - Some proposals have been made to use artificial corneas made of materials similar to lens materials in corneal transplant surgery. Recently, methods different from vision correction methods using contact lenses, corneas, or artificial corneal transplants have been proposed and are beginning to attract attention. That is, a means of incising the cornea and attaching a plastic-like section within the cornea JIIJI or on the surface of the corneal layer has begun to attract attention. For example, a patient's cornea is cut into a layered button shape, another person's cornea or a synthetic polymer compound prepared in advance into a desired lens is placed between the glabella within the corneal stroma, and then the cornea is sewn back to its original position.
kin) has been proposed. Additionally, keratomyelosis has been proposed, in which a patient's own cornea is cut into a layered button shape, frozen, cut into a desired lens using a lathe, and then sewn back onto the patient's eye. In addition, after cutting off another person's cornea, we used lathe processing under freezing to create a lens, and removed the patient's corneal epithelium.
Epikeratophagia (epikeraLo) transplanted to
phakia) has also been proposed. In addition, a corneal inlay has also been proposed, in which a lens is inserted into a bag made by ablating and incising the corneal stroma layer. Vision correction by these means is of the form shown in FIGS. 1 and 2, and is different from conventional corneal (or artificial corneal) transplant surgery methods. In Figures 1 and 2, 1 is a cornea, 2 is a lens for refractive keratoplasty, which is a section embedded in the corneal layer, and 3 is a lens for refractive keratoplasty, which is a section attached to the surface of the corneal layer. It is a lens for And this refractive keratoplasty. Research on lenses for use is being conducted in various fields. For example, Konuma, Hayashi et al.
1. Report on trial of glue-made lenses for fractive keratoblasti on rabbit eyes (1 eye, 1963, April, vol. 17,
No. 4, pages 453-457). However, it has been pointed out that this lens for refractive keratoplasty made of polymethyl methacrylate still has problems in terms of tissue reactions and the like. In addition, Tenri et al. reported that lenses for refractive keratoplasty were composed of galactose-based materials, glycerol-based materials, and hydroxy-based materials, and that among these, lenses composed of hydroxy-based materials were the best (Japanese). Co-Shi Academic Journal, 1971, Volume 13, No. 12, No. 1
(pages 40-144). Galactose methacrylate) (GAN^)
, glyceryl methacrylate-1-(ni 114^), 2-hydroxy 10vir methacrylate (2II P N^)
, water content 52% (water absorption 1) using ethylene glycol (HG) and N,N-dimethylformamide (DMF)
For refractive keratoplasty lenses made of galactose-based materials (10%), the transparency inside the corneal PAR decreases a month and a half after implantation, and intracorneal blood vessels begin to invade, causing corneal damage. Due to turbidity,
This junk! It has been pointed out that lenses for refractive keratoplasty made of -based materials are disqualified. Also, methyl methacrylate (88^), GIN^, 2
II P M^, tetraethylene glycosimethacrylate
1- Moisture content 45-76 using (TETR^) and EC
% (water absorption rate of 81-318%) or lenses for frac tip keratoplasty may lose their transparency a month after implantation into the angle MNI, and It has been pointed out that this is not a good thing, as blood vessels in the cornea begin to invade, clouding the cornea, and even causing ulcers on the cornea. and NN^, 2-hydroxyethyl methacrylate)
(211HMA), N-Bi=Lou2-t? o!
J tons (NVP) and moisture content 20~ using D14F
Refractive keratoplasty lenses made of 33% (water absorption rate 25-50%) hydroxy material,
It is reported that good results were not obtained with the galactose and glycerol-based substances that have a high water absorption rate, but good results were obtained with the hydroxy-type substances that have a low water absorption rate. . However, it has been pointed out that even in the case of lenses made of hydroxy-based materials or lenses for fractive keratoplasty, problems such as wrinkles occur, probably due to dehydration. In addition to the materials listed in E, materials made of, for example, 22-11E^ have been proposed, but this 2-II E M^
It has been reported that the refractive keratoplasty lenses manufactured by the company cause the cornea to become opaque. Lenses made of silicone or lenses for fractive gelatoplasty have also been proposed, but with these lenses, intracorneal blood vessels invade in about 1 month, which is another 17! Ij! fl
There was something about it. Although they achieve the same purpose as ophthalmological medical devices, refractive lenses and radoplasty lenses are made of materials that have been said to have excellent properties as contact lenses and dicorneal lenses. However, the existing ones were not sufficient.

[Disclosure of the invention]

At the stage when the inventor proceeded with the research based on the above information, in other words, based on the report on fire bombing, etc. At the stage when we were proceeding with the development of refractive cladoplasty lenses, we were proceeding with material development based on the viewpoint that materials with low water content (water absorption) were desirable as constituent materials for lenses for refractive cladoplasty. We have come to the conclusion that materials with low coefficients are not necessarily desirable. In other words, since the cornea itself basically has a high water content, it was revealed that it would be desirable to construct a lens for refractive keratoplasty using a material with a high water content. Therefore, first, as part of the I'm FJ, we conducted research to see if there were any proposals for lenses for frac-tive keratoplasty that were constructed using highly water-containing materials. became. This result shows that lenses for refractive keratoplasty with a water content of 88% using glyceryl methacrylate have a D
ol+Iman et al.'', and an experiment in which this refractive keratoplasty lens was implanted into the eye of a domestic rabbit has been reported (A archivesor (l
phLl+alehology vol, Fu, Fe
Although this refractive geladoblasty lens is made of excellent materials, it has been pointed out that biological reactions such as corneal edema occur during the early stages of implantation. There is. It has also been reported that when glyceryl methacrylate was made of a material containing triethylene glycol dimethacrylate as a crosslinking agent, corneal edema, corneal infiltration, and even angiogenesis occurred. In addition, the water content is 71% with polyvinylpyrrolidone as the main component.
The lens for refractive keratoplasty is 1ler.
An experiment was reported in which this refractive keratoplasty lens was implanted into the eye of a rabbit (lnvesLigaLiveOpbtl+a1m).
ology and Visual 5cien
ce Vol, 21. No, 1°107~115.1
981), and it has been pointed out that this refractive corneal plasty lens has an imbalance with the corneal stroma due to dehydration. For this reason, we recommend refractive keratin using highly water-containing materials!・I wondered if it would be possible to construct a plastic lens. Therefore, we created lenses for refractive keratoplasty using various high water content materials, and applied lenses for refractive keratoplasty constructed using a variety of high water content materials to the corneal layer of the rabbit eye. We reached the conclusion that the only option was to attach it to the corneal layer and to observe the results.
Tried this. As a result, when a refractive keratoplasty lens made of collagen, especially soluble collagen, with a water content of about 70 to 90% is used, problems such as corneal transparency do not occur at all, and the lens is immersed. It became clear to me. In addition, although it is not used as a lens for refractive Kera i/Plasty, in Japanese Patent Application Laid-Open No. 57-200152, a transparent film prepared from fermented and depolymerized or dispersion-purified skin collagen or cow's key is used for corneal molding. It has been reported that it has not been accepted for clinical practice. This collagen is obtained from animal skin at a relatively low cost on the continent, and is characterized by weak antigenicity compared to other proteins. Since this antigenic determinant is mainly found in telopeptides, atelocollagen excluding telopeptides has almost no problem with immune activity.Furthermore, when sterilized by irradiation with ultraviolet rays or radiation, it can be used as a long J (
Jl can be saved up to 1m. The meaning of soluble collagen is as follows. Although most natural collagen is insoluble, it can be dissolved in aqueous solutions of dilute acids such as acetic acid, bases such as sodium hydroxide, and dilute salts such as table salt, all with relatively low yields. Obtain a product with a rate of . The entire process of collagen extraction technology is as follows. This will be explained shortly, but it is well known. (a) Acid extraction method The collagen tissue of young animals, such as the skin of small animals, is approximately 1 to 2
% acid ii) soluble collagen. This collagen is 0.1N acetic acid or p I+ 3
, 6 in 0.15 molar citrate buffer is extracted with an aqueous solution of the acid 2-4. (b) Base Extraction Method The dermal layer of animal skin is extracted with 4% mol of monomethylamine and 15% of sodium sulfate for ~15 days at room temperature.
immersed in a solution of sulfur and lithium hydroxide. The hide is washed with water to remove the base and then 0.
Extracted by stirring in IN acetic acid-0.1 molar HaCl (pH 2.8). Almost all the hides dissolve and a viscous solution is obtained. This collagen is collected in a centrifuge, precipitated by increasing pl+ to 4-5, and washed with water. After dehydration with ethanol, the collagen is treated with an ethanol-ether mixture fI solution to remove fat. After air 92 drying, the collagen is dissolved in an acidic aqueous solution of 0112-4 and filtered through a filter. Collagen is precipitated at p114-5, collected in a centrifuge, and finally collected at 4-1 in an acidic aqueous solution of 0112-4.
0% collagen is 11N. (e) Salt extraction method Collagen can be extracted from tissue by treatment with a salt solution, such as a dilute Na11 solution. (d) Enzyme Extraction Method The washed and dehaired hide or skin is cut into small pieces of processable size, dissolved in an acidic aqueous solution in the presence of proteinaceous enzymes (other than collagenase), and viscous. Make a solution. Incidentally, suitable enzymes include pepsin, 1-ribusin, pronase, and protase. This digestion yields two fractions, one of which is the insoluble solid fraction, which is discarded, and the other of the solution or soluble fraction, which is made up as follows. This solution is brought to a p11 of about 10.0 to denature any remaining active enzyme and neutralized to a p11 of about 6.0-7.0. Atelocollagen precipitates in this 9+1, leaving digested telobebutide, other 1U proteins, saccharides, mucopolysaccharides, etc. in solution. This atelocollagen usually dissolves at pH 2 to 3 and
It is purified by repeating reprecipitation at 116-7. The extracted collagen is then washed with ethanol for a solvent delipidation process and to remove lipid components and excess water. The collagen is defatted by treatment with an ethanol-ethyl ether mixture, removed as a viscous solid by a cheesecloth filter, air-dried, and then converted into a gel by dissolving in an aqueous solution of an acid with p+1 ~3. be done. In addition to soluble collagen, for example, hyaloalic acid,
Mucopolysaccharides such as chondroitin sulfate and other strength-improving materials may also be used as subcomponents. (Example 11) A 10% transparent collagen gel was obtained by dissolving collagen in an acidic solution of p++ approximately 3. This was placed in the four parts of a plastic mold, defoamed under reduced pressure, and then removed from the mold. Press the convex part onto the collagen gel,
After the entire mold was filled with nitrogen, a crosslinking reaction was carried out by irradiating cobalt 60 for 211 i, and the total radiation loss of cobalt 60 was 1 megarat. The collagen lenses thus obtained were swollen with phosphate buffer, transferred to physiological saline, and stored. Note that this collagen lens has a water content of 90%, is optically transparent, and is highly flexible. The collagen lens to be stored was taken out and punched into six rings with an i.refin diameter to form a lens for cornial inlay, which was inserted into a detached pocket in the corneal f1 layer of a white rabbit. Insertion (after li, rr change over time using slit lamp, etc.)
The corneal trap was removed at J4 examination and 20 months after surgery, and the effect on corneal tissue MB was examined using a scanning electron microscope. As a result, this refractive geladoblasti lens is guaranteed to be transparent, has good optical properties, and has no inflammatory reaction.

[Example 2] The same procedure as in Example 1 was conducted using the same mixture of 7% collagen and 5% polyvinyl alcohol as in Example 1. ■ Shrimp with a water content of 89%, optically transparent, and highly flexible A lens for keratophagia was obtained, placed on the corneal epithelium of an albino rabbit, and sewn. Postoperative results showed that the transparency of this lens for refractive keratoplasty was guaranteed, the optical properties were good, there was no inflammatory reaction, and no similar abnormalities were observed. [Comparative Example 1] As a result of carrying out the same procedure as in Example 1 using a material with a water content of 35% mainly composed of 2-+1EN^, this lens for refractive keratoplasty showed corneal opacity within 1 month after the surgery. In addition, blood vessel invasion was observed.

[Comparative Example 2] As a result of carrying out the same procedure as in Example ① using a material with a moisture content of 77% containing NVP as the main component, this refractive keratin l-
With the No. 7 LASTY lens, corneal transparency decreased 11 months after surgery. (Comparative Example 3) A lens obtained in the same manner as in Comparative Example 2 was sewn onto the cornea of a white rabbit in the same manner as in Example 2. The ratio of 1:1 caused corneal opacity.

[Brief explanation of the drawing]

FIGS. 1 and 2 are schematic diagrams of lenses for refractive keratoplasty. 1... Cornea, 2.3... Lens for refractive keratoplasty.

Claims (1)

[Claims] A lens for refractive keratoplasty that is attached on or within the corneal layer, and this lens for refractive keratoplasty has a water content of about 70 to 90%, with the remainder mainly composed of soluble collagen. A lens for refractive keratoplasty that is characterized by: