Eye drops for the treatment of endothelial-epithelial corneal dystrophy

 

(57) Abstract:

The invention relates to the field of medicine. Observed in living organisms free-radical oxidation, responsible for the occurrence of pathological conditions, constrained by antioxidants, converting radicals into inactive compounds that interrupt the chain reaction and thereby eliminate or reduce the negative impact of prooxidants on physiological processes. Eye drops, which include a complex of 9 antioxidant drugs: unithiol, zinc sulfate, ascorbic acid, vitamin E 20% solution of albumin, uric acid, allopurinol, dimethyl sulfoxide, ethyl alcohol 96^o, sodium Selenite, allow to solve the problem. Eye drops in the treatment of various stages updaterule-epidemiology dystrophy more fully and quickly allow you to restore the epithelial defect, nausea signs of corneal syndrome (pain, photophobia, lacrimation), to improve visual acuity. table 2.

The invention relates to medicine, namely to ophthalmology, and can be used in the treatment of patients with endothelial-epithelial corneal dystrophy.

Endothelial-epithelial destroyed damage to the endothelial cells of the cornea due to previous eye operations with the opening of the eyeball (on cataract, glaucoma and other) or significant injury of the cornea during a perforated injured eye. Widely used in ophthalmic practice, the implantation of artificial lenses after cataract extraction is one of the factors that increase the frequency of EEDR.

AADR has various stages, usually accompanied by long-term pain, photophobia, lacrimation, significantly reduces vision due to defects of the corneal epithelium, stromal edema and degenerative process in the endothelium of the cornea is the main element, which is responsible for the maintenance of normal hydration of the cornea.

There are a large number of works devoted to research methods and means of operative and conservative (medical) treatment EEDR.

Among the methods of surgical treatment known in some sections of the endothelium, various types of keratoplasty and depertment, interlayer collagenoplasty, laser pantagonia of the cornea.

Currently, among the surgical methods of treatment EEDR known total rear cryopexy, phototherapeutic keratectomy with excimer laser, intralamellar keratopathy of polyacrylamid glycosaminoglycanes.

However, these methods of surgical treatment EEDR not found wide application because have low efficiency, the complexity of the process, the need to attract highly skilled professionals and use of expensive equipment, the risk of postoperative complications.

The well-known drugs include eye drops "Intertank". However, using this tool is mainly for the pharmaceutical protection of the graft after surgery, treatment of keratitis, deep erosions and ulcers of the cornea. When treating AEDR data eye drops because of their lack of effectiveness is used only in the initial stages (I, II) development of pathological process.

However, it is known that extremely important in the development of physiological and pathological processes in vivo are the processes of lipid peroxidation (LPO), occurring mainly in the lipid biosloi cell membranes. Development processes the FLOOR depends on the ratio of the content in the body of prooxidants (reactive oxygen species (ROS) and free radicals (FR)), whose action on living cells is the tov comes to the effect on the rate of biological processes in the cell. The presence of prooxidants in physiological concentrations is useful for the body as it activates metabolic processes. In the hearth as the excessive accumulation of prooxidants occurs, as a rule, "oxidative stress".

It is established that in the hearth of the "oxidative stress" prooxidants can cause the tissues of numerous metabolic and structural changes, resulting in:

- the formation of lipid peroxides with consequent damage to cell membranes;

- the release of the membranes arachnoideum acid (one of the mediators of inflammation);

activation of fibroblasts with perforated eye injuries, which leads to vitreoretinal proliferation, the formation of a rough inner commissure and the possibility of detachment of the retina;

- inactivation of protease inhibitor, which is 90% control of proteolytic activity in blood and tissues, resulting in activation of tissue proteases;

activation alsoreported in cells and increased edema;

- strengthening processes aminocarbonyl interaction between proteins and carbohydrates with the formation of insoluble complexes, leading to increased levels of glucose in the cells;

- Neporozhny biological systems inevitably, to some extent, always run to maintain a radical oxidation process, with specified important in maintaining the structural and functional homeostasis. Retention reactions FLOOR on a stationary (but not always increasing) the physiological level is the various mechanisms of antioxidant protection. The failure of the antiradical and antipersonnel protection is an important pathogenetic factor in many pathological conditions, including EEDR.

Thus, observed in the body of free radical oxidation is constrained by antioxidants, converting radicals into inactive compounds that interrupt the chain reaction and thereby eliminate or reduce the negative effects of prooxidants on physiological processes.

In connection with the foregoing, attempts have been made use in the treatment of EEDR antioxidants such as vitamin E (10% oil solution), taufon (4% solution), ariad (0,2% solution in drops). However, the treatment of the above mentioned equipment related to the number of antioxidants as monotherapy is limited due to their extremely low efficiency.

The closest in composition and mechanism of action is of a highly effective tool for the treatment of various stages endothelial-epithelial dystrophy of the cornea.

The objective is achieved through the use of eye drops, which include a complex of antioxidant drugs, including the acceptors of free radicals (vitamin E, ascorbic acid, dimethyl sulfoxide, ethyl alcohol), reducing their thiols (unithiol) and blockers of initiation of free radical processes (uric acid, allopurinol, zinc sulfate, sodium Selenite).

Specified positive impact of complex antioxidant drugs can be explained as follows.

Vitamin E is a fat-soluble substance that is able to show properties only antioxidant in the lipid environment, while the formation of free radicals and observed in connection with this pathological changes in the lipid and aqueous environments. When dissolved vitamin E in the albumin is an opportunity to mix it with water-soluble drugs.

- tocopherol (vitamin E) more effectively protects biosubstrate from oxidation only in combination with water-soluble antioxidants, in particular vitamin C, which acts as a trap hydrophilic free radicals (hypohalites (ClO^-and others), H₂ABOUT₂, RO

Irreversible destruction of ascorbic acid inhibited under the influence of unithiol and uric acid.

Ethyl alcohol in small quantities is also an antioxidant and links the radicals HE^..

Of particular importance in the developed complex have a low molecular weight thiols, in particular unithiol, which forms a redox system, restoring the oxidized form of lipophilic and hydrophilic acceptors of free radicals. In addition, the complex of unithiol stabilizes enzymatic antioxidants (superoxidedismutase, catalase, glutathione - S-transferase, etc.).

In the presence of metals of variable valence ascorbic acid and other biosubstrate be a powerful prooxidants (free radicals). This prevents uric acid, which binds the free variable valence metal, and zinc, stabilizing the structure of their electron shells.

Introduced in the complex sodium Selenite necessary for stabilization of metals of variable valence and selenium-dependent lusignolo the radical anion. Dimethyl sulfoxide is a solvent allopurinol and acceptor of HE^.and radicals.

The possibility of achieving the goal of the invention is proved by the following examples.

Example 1. Preparation of eye drops.

Indoors sterile Boxing in compliance with the requirements of asepsis and antisepsis in chemically clean sterile glass mixed sample of zinc sulfate in the amount of 6.0 mg, uric acid, 20 mg of sodium Selenite to 0.3 mg) was Gradually added bidistilled water in an amount of 10 ml, was mixed components sterile glass rod until full dissolution.

Ampoule of 5% aqueous solution of unithiol 5 ml (manufactured by ICN October) and 5% aqueous ascorbic acid solution (manufactured by ICN October) were processed outside 96^oethanol, dissected and disposable insulin syringe were taken at 0.25 ml and 0.5 ml of the drugs, respectively. Official solutions are successively introduced into the previously prepared solution of antioxidants. To the mixture was added 0.2 ml 96^oethyl alcohol.

Separately preparing a portion of the substance of allopurinol in the amount of 7 mg in sterile glass containers was mixed with 1 ml of undiluted dim lopurinol in Dimexidum was added to a mixture of antioxidants.

After the treatment with ethyl alcohol was opened ampoule 10% oil solution-tocopherol acetate (vitamin E) in a volume of 1 ml (manufacturing ICN October) and was dissolved its contents in 2 ml of 20% aqueous solution of albumin. The resulting solution was mixed with the previously prepared composition of antioxidants.

The mixture of dissolved components were poured into sterile glass chemical volumetric flask. The amount of content brought up to 20 ml by adding water for injection. The mixture was dissolved and well mixed. The resulting solution was filtered and packaged in sterile vials of 5 ml Bottles corked with sterile rubber stoppers.

Example 2. Use eye drops in the treatment of EEDR.

Eye drops used to treat 14 patients with edematous form EEDR. 8 people had III bullous stage (total) EEDR. The reason for the development of EEDR in 6 cases was extracapsular cataract extraction with artificial optical lens (IOL), 3 cases of cataract extraction without installing IODINE in 4 observations - various antiglaucoma operations, and only 1 patient noted the primary AADR for no apparent reason. The age of patients ranged from 50 to 60 years - 7 people, from 60 to 70 years - 5 person(pain, photophobia, lacrimation) of different severity. The disease duration was: 6 months - 1 person, up to 1 year - 1 person over 3 years to 5 people more than 5 years 4 to 10 years - 2 persons, more than 10 years - 1 person. Therefore, the majority of patients were suffering from the specified disease for more than three years. Visual acuity in patients was equal to: the movement of a hand of a person with 6 people, 0,01-0,03 for 3 people, 0,04-0,06 3 people 0,07-0,1 2 people.

Prepared eye drops were prescribed to patients in konyunktivalny cavity of the affected eye 2 drops 6 times a day for 2-4 weeks to complete epithelialization of the cornea and corneal edema syndrome.

All patients were under constant surveillance with ophthalmologic examination after 1 day, 3 days, 1 week and then at intervals of 1 week.

During the observations were recorded:

the degree of corneal syndrome (pain, photophobia, lacrimation);

- visual acuity;

- the length of the defects of the corneal epithelium;

- the size and number of bubbles;

the degree of swelling of the stroma;

the ingrowth of blood vessels into the cornea.

The examination was performed using a slit lamp after putting in the eye of the solution fluorescein NAT is applied eye drops and tools of the prototype in the treatment of EEDR was evaluated by the degree of epithelialization of the cornea and visual acuity at the end of treatment.

The results obtained in the treatment of patients with eye drops and a tool prototype within two weeks, are presented in table. 1 and 2.

As can be seen, in the case of the use of eye drops (complex of antioxidants) in two weeks, complete epithelialization occurred in 11 cases out of 14.

Thus, in the case of the use of eye drops complete epithelialization was observed in 79% of patients, partial in 7%, did not come - at 14%. When using only vitamin E. these figures were respectively 25,0%, 8.3%, and 66.7 per cent. The effectiveness of eye drops (complex antioxidant preparations) 3 times the efficiency of the means of the prototype and allows to achieve full recovery of defects in the epithelium.

All observed patients after application of eye drops (complex of antioxidants) within two weeks disappeared completely signs of corneal syndrome (pain, photophobia, lacrimation).

Presented in table. 2 the data shows that in the case of using the generated eye drops vision improved in three patients: two (14,3%) 0,01-0,03, one (7.1 per cent) 0,04-0,06. When using the prototype vision improved by 0.01-0.03 to 3 people (25,0%). Given the low overwriteing result. Thus, in the case of applying the eye drops visual acuity in patients with AADR is not adversely affected.

With long-term use of eye drops side effects, and toxic and allergic reactions are not detected.

The claimed invention satisfies the criterion of "novelty", as first proved the effectiveness of the complex of antioxidant drugs in pharmacological correction of "oxidative stress" in the pathological focus, refined part of the eye drops for the treatment of patients with different stages endothelial-epithelial dystrophy of the cornea.

The claimed invention satisfies the criterion of "inventive step" as available information there are no data from which would be obvious a set of antioxidant drugs and their combinations, the use of which allows more effective treatment of severe chronic diseases of the organ of vision, as EEDR.

The criterion of "suitability for industrial application" is proved by the results of research and testing in the treatment of 14 patients with various stages of EEDR showing that eye drops can be widely applied in Kenya, easily prepared from available official preparations.

The source of information

1. Morozov, C. I., Yakovlev A. A. Handbook "Pharmacotherapy of eye diseases. Topic: corneal dystrophy. - M., 1998. - S. 332.

Eye drops for the treatment of endothelial-epithelial corneal dystrophy, containing vitamin E, characterized in that it further contains unithiol, zinc sulfate, ascorbic acid, uric acid, allopurinol, dimethyl sulfoxide, ethyl alcohol, sodium Selenite, with the following content of components in 20 ml of a solution:

Unital (5% solution) - 0.25 ml

Zinc sulfate - 6.0 mg

Ascorbic acid (5% solution) and 0.5 ml

Vitamin E 100 mg

Uric acid - 20 mg

Allopurinol - 7 mg

Dimethyl sulfoxide - 1 ml

Ethyl alcohol 96^o0.2 ml

Sodium Selenite - 0.3 mg

Water - Ostalnoe