RU2251394C2 - Composition and method for manufacturing curative soft contact lens - Google Patents

Abstract

FIELD: medicine, ophthalmology.

SUBSTANCE: the suggested composition includes gelatin, glucose, hydroxide of alkaline metal, distilled water at certain ratios. As hydroxide of alkaline metal one should apply sodium hydroxides (NaOH), potassium hydroxides (KOH) or lithium hydroxides (LiOH). Composition should be prepared due to adding gelatin into aqueous glucose solution to obtain homogeneous solution, then one should supplement hydroxide of alkaline metal as 3 M aqueous solution, pH of composition is increased up to 10.5-11.5. The obtained composition should be heated at hot water bath for 2-3 min at 94-98 C, then it should be cooled with cold water for 3-5 min up to 20 C. Heating and cooling cycle should be repeated 4-6 times. On finishing the process composition's pH is decreased up to 7.5-8.5. Composition should be poured into vials to be dried and kept at room temperature. The process lasts for 5-7 d. The obtained curative, soft contact lens should be sterilized by placing them together with the form for 1 h into 96°-ethanol solution, to be dried by not separating against the form and stored in dry sealed vials out of dark glass. Before application lens should be impregnated in isotonic solution of sodium chloride (NaCl) for swelling to separate then against the form and rinsed 4-5 times in 0.9%-NaCl solution. The innovation provides efficient ocular protection in case of burns, traumas and chronic diseases.

EFFECT: higher efficiency of manufacturing and application.

3 cl, 3 ex

Description

The invention relates to medicine, in particular ophthalmology, and can be used to treat burns, chronic diseases and eye injuries.

Soft contact lenses (MKL) with a high water content have proven themselves in the treatment of chronic diseases and eye injuries. The healing properties of MKL are related to their ability to cover the damaged cornea as a dressing, protecting the wound surface from infection. In addition, MCLs are capable of absorbing significant amounts of drugs, creating effective therapeutic concentrations of drugs in the tissues of the anterior eye when using them for therapeutic purposes. Due to this, therapeutic soft contact lenses (LMLC) are increasingly used in the treatment of eye burns, dystrophic diseases of the cornea and keratitis, as well as to relieve pain from corneal sutures.

In addition, the experience of local wars in Afghanistan and Chechnya showed that the use of LMLC can reduce the need for the number of sutures applied to the cornea and sclera, and for small wounds, it is possible to eliminate the suturing, replacing it with LMLC soaked with antibiotic.

The experience of using LMLC in ophthalmic practice has made it possible to establish the basic requirements for this type of lens:

- high water content (not less than 55%);

- diameter of at least 14.5 mm;

- the possibility of continuous wearing for at least 7 days;

- the ability to absorb antibiotics and other drugs from solutions, and then release them when placing LMLC on the cornea of the eye.

Known polyacrylamide MKL [1] with a water content of 84-87%, satisfactorily tolerated with prolonged use as corrective or therapeutic lenses. These MCLs are prepared by polymerization of acrylamide in closed form in the presence of a crosslinking agent and a polymerization initiator. The disadvantage of polyacrylamide MCLs produced by this method is the presence of extremely toxic residual monomeric acrylamide in their composition in an amount of up to 0.5%, which requires careful washing of the lenses with water after removing them from the mold in compliance with all safety requirements, which significantly complicates the technological the manufacturing process of these lenses.

Also known are LMLCs obtained by alkaline treatment of lenses based on polymers and copolymers of 2-hydroxyethyl methacrylate [2]. With this treatment, the water content of LMLC increases to 83%. Carboxyl groups appearing with the indicated processing technology in the polymer structure increase the ability of these lenses to effectively bind drugs through the formation of hydrogen or ionic bonds. A disadvantage of the LMLC of the indicated type is the too complicated technology for their manufacture, which actually includes three stages: the manufacture of a polymer billet, the time-consuming turning of a lens of a given configuration from a polymer billet, and the processing of a machined lens with an alkali solution.

The closest in composition to the present invention is a composition consisting of an aqueous solution of gelatin and a modifier (structurant), which is used as a tanning agent LIKI-19 - (N, N, N ', N'-tetraisopropoxymethyl) diamide malonic acid [3], adopted as a prototype. The manufacturing process of MKL in this case involves placing the composition in an open form from polymethylmethacrylate and structuring the gelatin for 24 hours at room temperature or for 1-2 hours at a temperature of 40-50 ° C. A lens made in this way has a very high water content (up to 90%), which significantly increases its oxygen permeability compared to other hydrogels with a lower water content. The protein nature of gelatin determines the biological activity of the considered MKL and the ability to effectively absorb drugs. The disadvantage of gelatin MKL, modified LIKI-19, is their increased stiffness, which makes these lenses not comfortable enough for patients, especially with prolonged wear [3]. The high rigidity of gelatin MKL, despite their high water content, is probably due to the chemical nature of the used structure-forming agent - LIKI-19, which forms short stiff crosslinks between protein macromolecules. The considered method for producing lenses from gelatin is, by technical nature, closest to the present invention and adopted as a prototype.

The aim of the invention is to provide a composition for therapeutic soft contact lenses, providing increased efficiency in the treatment of pathology of the cornea of the eye, and a method of manufacturing lenses from it.

This goal is achieved due to the fact that for the manufacture of LMLC, a composition is used that includes, in addition to gelatin, additives - glucose, alkali metal hydroxide and water. A method of manufacturing LMLC using the specified composition involves heat treatment of the composition, including several heating and subsequent cooling cycles, and pouring it into standard open forms of polytetrafluoroethylene, in which the lens is formed as a result of drying and final structuring of the material.

Structuring of the claimed composition with the formation of a three-dimensional network occurs as a result of a series of successive chemical transformations proceeding according to the Maillard reaction mechanism, which is a process of non-enzymatic glycation of free amino groups of amino acids or proteins by aldoses or ketoses. In the first stage, aldoses or ketoses interact with the amino groups of amino acids or proteins to form Schiff bases. The resulting aldimines or ketimines undergo intramolecular rearrangement with the formation of Amadori compounds. Subsequent reactions of dehydration, condensation, spontaneous decomposition of Amadori compounds to more active sugars, fragmentation, oxidation and cyclization lead to the appearance of a variety of heterocyclic compounds. If free amino groups belong to proteins or other macromolecules, then in the presence of aldoses or ketosis, the macromolecules crosslink. Depending on the depth of glycation, the Maillard reaction products are weakly or strongly colored compounds with high biological activity, which allows them to be used as therapeutic agents for wound healing [4].

The essence of the invention lies in the fact that the proposed composition includes gelatin and additional additives with the following number of components (parts by weight):

gelatin - 4.0-4.5;

glucose - 8.0-11.0;

alkali metal hydroxide - 0.2-0.3;

distilled water - 83.5-88.0.

In the proposed composition, glucose acts as an aldose in the Maillard reaction. Sodium, potassium or lithium hydroxides are used as alkali metal hydroxide. The presence in the composition of the composition of an alkali metal hydroxide in the specified amount ensures the establishment of an optimal pH of the reaction mixture (10.5-11.5), at which the reaction rate is maximum. In addition, alkali metal hydroxide converts the carboxyl-containing products formed during the reaction into a water-soluble salt form, which prevents premature structuring of the composition during acyclic processing (heating - cooling).

The composition is prepared by adding gelatin to an aqueous glucose solution.

After obtaining a homogeneous solution, alkali metal hydroxide is added in the form of a 3 M aqueous solution. In this case, the pH of the composition rises to 10.5-11.5. The vessel with the obtained composition is subjected to heating in a water bath for 2-3 minutes at a temperature of 94-98 ° C, and then cooled with cold water for 3-5 minutes to 20 ° C. The heating and cooling cycle is repeated 4-6 times. Carrying out heat treatment in the form of several short heating-cooling cycles contributes to a more efficient accumulation of active products in the reaction system that accelerate and deepen the crosslinking of gelatin at low temperature. After completion of the process, the pH of the composition drops to 7.5-8.5.

The composition thus treated is poured into standard open forms of polytetrafluoroethylene having the required radius of curvature, diameter and depth, where it is dried and further structured at room temperature. The process continues for 5-7 days. The obtained LMLCs are sterilized by placing them together with the form for 1 hour in a 96 ° solution of ethyl alcohol. Then the lenses are dried, not separating from the mold, and stored in dry, sealed cans of dark glass. Before use, the lenses are immersed in an isotonic solution of sodium chloride (NaCl) for swelling, after which they are separated from the mold and washed 4-5 times with a solution of NaCl. After that, LMLC can be used.

LMLCs made using the proposed composition and a method of manufacturing lenses from it do not contain toxic substances, have good mechanical properties, are comfortable for prolonged wear, due to increased elasticity and high water content (75-85%), have a pronounced therapeutic effect.

The achievement of the objectives of the invention is confirmed by the following examples.

Example 1. The manufacture of LMLC from the proposed composition

A 5% gelatin solution in 10 ml of a 10% aqueous glucose solution is prepared in a vessel. After obtaining a homogeneous solution, 0.2 ml of a 3 M NaOH solution is added to it (the pH of the solution becomes 11.2).

The vessel with the mixture is heated in a water bath for 2 minutes at a temperature of 95 ° C and then cooled with cold water for 4 minutes to 20 ° C. The specified cycle of heating and cooling is repeated 5 times. After 5 cycles of heat treatment, the pH of the solution becomes 8.0.

Then the mixture is poured into standard open forms of polytetrafluoroethylene and kept in these forms at room temperature for 7 days for drying and further structuring. After this, the forms together with the lenses are placed for 1 h in a 96 ° ethanol solution for sterilization. Then the finished lenses together with the forms are placed in dry dark glass jars for storage.

Before use, the lenses together with the forms are placed in a Petri dish with a 0.9% NaCl solution for swelling. After a few minutes, the lenses are separated from the mold and washed 5 times in a 0.9% NaCl solution.

Example 2. Testing LMLC in the treatment of injuries of the cornea and sclera of the eye

Patient P., 47 years old, was injured in the right eye by shattered glass during a car accident. After surgical treatment with the removal of the damaged lens and suturing the wounds of the cornea and sclera, the patient is worried about severe pain from sutures. The cosmetic MKL used in this case (manufactured by Wesley-Jessen, USA) did not completely cover the scleral sutures, since its diameter is 14.5 mm, and the sutures of the patient on the sclera reach the equator region. The indicated lens, which the patient wore for 2 days, gave her only partial relief. After replacing the specified lens with gelatin LMLC made from the claimed composition using the proposed method, a radius of 11.5 mm and a diameter of 18 mm, the patient was relieved. The seams ceased to bother the patient. After 6 days, the gelatin lens was removed and a new gelatin lens was dressed. The patient continued to instill drops of maxitrol and 1% atropine in the eye. After removal of the second lens after 6 days, the scleral sutures and part of the cornea were removed. Cosmetic MKL (manufactured by Wesley-Jessen, USA) was dressed in the eye.

Example 3. Testing LMLC in the treatment of endothelial-epithelial dystrophy of the cornea of the eye

Patient K., 65 years old, underwent surgery with implantation of an artificial lens. After the operation, a complication appeared in the form of endothelial-epithelial corneal dystrophy: corneal edema, corneal erosion, epithelial blisters and severe pain corneal syndrome. The patient was dressed gelatin LMLC made from the claimed composition using the proposed method. The pain syndrome has completely disappeared. The patient was instilled with chloramphenicol with heparin. When examining the patient after 7 days, complete epithelialization of the cornea was noted, although its edema persisted. After the inspection, a new gelatin LMKL was dressed.

The claimed invention satisfies the criterion of "novelty", since it was first proposed for the manufacture of therapeutic soft contact lenses a composition comprising gelatin and additives, in which, owing to the occurrence of structuring processes according to the Maillard reaction mechanism, gelatin is crosslinked and a method for producing LMLC from it.

The claimed invention meets the criterion of "inventive step", since there is no information in known sources of information from which it would be obvious the possibility of using this composition for the manufacture of LMLC and the technology for manufacturing lenses from it.

Compliance with the criterion of "suitability for industrial use" is proved by the results of testing lenses in the treatment of various eye diseases, from which it is clear that they have a pronounced therapeutic effect. The proposed composition includes cheap domestic materials, and the lenses obtained from it do not contain toxic substances, comfortable for prolonged wear due to sufficient elasticity and high water content. The proposed method of manufacturing LMKL is simple, does not require the use of expensive equipment and special training of personnel.

List of references

1. Development of medical and technical requirements for soft contact lenses of continuous wearing: Report on research (final) / VMedA, head N.A. Ushakov, St. Petersburg, 1990, 34 p.

2. RF patent No. 2173868. A method of manufacturing therapeutic contact lenses. Application No. 99117875, declared on 08/18/1999, priority 18/08/1999

3. RF patent. No. 2144537. Composition and method for manufacturing a contact lens. Application No. 96113245, filed July 4, 1996, priority July 4, 1996.

4. Telegin T.A., Davidyants S.B. Maillard reaction: aminocarbonyl interactions in vivo and melanoidins // Successes in Biological Chemistry. T. 35, 1995, S. 229-266.

Claims (3)

1. Composition for therapeutic soft contact lenses, including gelatin and additives, characterized in that as additives it contains glucose, alkali metal hydroxide, distilled water with the following number of components, parts by weight: gelatin 4.0-4.5; glucose 8.0-11.0; alkali metal hydroxide 0.2-0.3; distilled water 83.5-88.0. 2. The composition according to claim 1, characterized in that the alkali metal hydroxide contains sodium hydroxide NaOH, potassium KOH or lithium LiOH. 3. A method of manufacturing a therapeutic soft contact lens in open form from polymethyl methacrylate, characterized in that the composition according to claim 1, which is a 5% solution of gelatin in 10 ml of a 10% aqueous glucose solution with the addition of 0.2 ml of 3 M alkali metal hydroxide solution is subjected to 4-6 heat treatment cycles, including heating in a water bath for 2-3 minutes to a temperature of 94-98 ° C and subsequent cooling with cold water for 3-5 minutes to 20 ° C, poured into molds and incubated in them for 5-7 days at room temperature, then they are sterilized in a 96 ° solution of ethyl alcohol for 1 h, dried and stored, not separated from the form in dry, closed dark glass jars, and before use, the lenses are separated from the forms by immersion in an isotonic sodium chloride solution and washed 4-5 times with 0 , 9% sodium chloride solution.