RU2485939C1 - Disulfiram and taurine-containing ophthalmological medication in form of eye drops - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of ophthalmology. Ophthalmological medication in form of eye drops, contains 0.2-0.5 wt % of disulfiram, dissolved in pharmaceutically acceptable water-based carrier, 0.5-2.0 wt % of hydroxypropyl cyclodextrin, 2.0-5.0 wt % of taurine; agent, which ensures required resin condition, containing sodium chloride, sodium monohydrophosphate and dihydrophosphate, and methylparaben (nipagin) as a preservative.

EFFECT: invention ensures effective treatment of pathological conditions of eyes, such as cataract, glaucoma, ophthalmological hypertension and traumatic injuries of cornea, extends arsenal of existing preparations in form of eye drops.

6 cl, 5 tbl, 2 dwg, 5 ex

Description

The invention relates to pharmacology and ophthalmology and can be used to create a drug for the treatment of pathological conditions of the eyes selected from cataracts, glaucoma, ophthalmic hypertension and traumatic damage to the cornea in patients of different ages.

Prior Art Information

In the broadest sense, the term "cataract" defines any change in optical uniformity or a decrease in the transparency of the lens of the eye. Many factors are involved in the etiology of cataracts, such as heredity, aging, diabetes, smoking, nutrition, the cumulative effect of X-ray and UV radiation, and endocrine and / or enzymatic imbalance in the body.

The most significant among the chemical compounds that cause cataracts are oxygen radical particles, for example, formed under the influence of UV radiation present in the spectrum of sunlight. Such particles disrupt the lens homeostasis by increasing the level of Ca ^{2+ ions} in the lens, which, in particular, activates calcium-dependent proteases, for example, calpain. This leads to the destruction of the lens proteins, such as crystallins, and, ultimately, to its clouding.

The proposed mechanism is not the only one, but it allows you to choose targets for drugs and develop treatment strategies. In particular, one of the known and very safe antioxidants that bind hydroxyl, peroxide, peroxynitrile radicals is disulfiram, a dimer of diethyldithiocarbamate, which itself can also eliminate the action of hydroxyl radicals and inhibit lipid peroxidation. However, the low solubility of disulfiram in water, its instability in neutral aqueous media and the inability to penetrate through the cornea are significant obstacles to its use in ophthalmology.

EP 2238978 (published October 13, 2010) discloses a pharmaceutical composition comprising a disulfiram and cyclodextrin inclusion complex, optionally containing uncomplexed disulfiram and one or more pharmaceutically acceptable carriers. In the embodiments of the invention, liquid parenteral, tabletted oral and pelletized subcutaneous forms of the preparation for the treatment of alcohol and cocaine addiction are disclosed, containing 15-80 wt.% Of disulfiram complex.

In an article by Nagai N. et al. "Delay in ICR / f Rat Lens Opacification by the Instillation of Eye Drops Containing Disulfiram and Hydroxypropyl-β-cyclodextrin Inclusion Complex" (Biol. Pharm. Bull. Vol. 30 (8) (2007). P.1529-1534, publ. 06.06.2007) on the rat model ICR / f (line with a cataract inherited by the recessive type) the following is shown. By the 77th day of life of animals in groups receiving eye drops containing disulfiram, lens opacities were 35-45% less pronounced than in animals of the control group receiving isotonic saline, in which a clearly observed cataract had already formed by the 75th day of life. From the 30th day of life, animals from the experimental groups were injected twice a day with 50 μl drops containing 0.25-0.50% disulfiram, 3.0-5.0% 2-hydroxypropyl-β-cyclodextrin and 0.1% in the left eye hydroxypropyl methylcellulose.

In the article by Nagai N., Ito Y., Takeuchi N. “Effect of Disulfiram Eye Drops on Lipid Peroxide Formation via Excessive Nitric Oxide in Lenses of Hereditary Cataract ICR / f Rats” (Biol. Pharm. Bull. Vol. 31 (5) (2008) P.981-985, publ. 13.02.2008) it is shown that the introduction of drops containing 0.25-0.50% disulfiram, 3.0-5.0% 2-hydroxypropyl-β-cyclodextrin and 0 , 1% hydroxypropyl methylcellulose by the 77th day of life of animals 1.5-2 times increases the pixel transparency of the lens and in the same proportion reduces the content of Ca ^{2+ ions} in the lens. At the same time, the concentration of NO in the lens decreases 1.5 times and the content of lipid peroxides decreases 2 times.

The authors consider the results disclosed in both articles as the basis for further studies of such disulfiram drugs as potential anti-cataract medications for aging.

In the article by Nagai N., Ito Y., Takeuchi N. "Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-cataract Effect of Eye Drops Containing Disulfiram and Low-Substituted Methylcellulose Using ICR / f Rat Lens as a Hereditary Cataract Model" (Biol. Pharm Bull. Vol. 35 (2) (2012). P. 239-245, published on 11.24.2011) on the ICR / f rat model it was shown that the administration of eye drops containing 0.5% disulfiram, 5% 2-hydroxy -propyl-β-cyclodextrin, 0.1% hydroxypropyl methylcellulose and 2.0% methylcellulose, in the interval from 77 to 84 days of life of male model animals, maintain the pixel transparency of the lens, exceeding 2-3 times the figure in the control group. It was also found that a drug containing clinical cellulose in a clinical concentration (2.0%) is more effective than a similar drug described in previous articles. The authors attribute this fact to gelation when the temperature rises to eye temperature (about 35 ° C), which increases the retention time of eye drops on the surface of the cornea.

Various ophthalmic preparations containing taurine are known in the art. In the application EP 0778021 (publ. 11.06.1997) disclosed eye drops to accelerate the regeneration of the cornea after damage, containing 0.5-3.0% taurine, sodium chloride, potassium chloride and sodium bicarbonate having a pH from 5.5 to 8, 0 and osmotic pressure from 250 to 450 mOsm.

In the patent RU 2127099 (publ. 10.03.1999) disclosed eye drops containing (in wt.%):

sodium succinate hexahydrate 1.91 sodium citrate 5.5-aq 0.40 sorbitol 0.80 sodium chloride 0.31 L-glutamic acid 0.015 riboflavin mononucleotide phosphate 0.02 benzalkonium chloride 0.014 glucose 0.30 taurine 4 g distilled water for injection rest.

The use of drops can improve energy metabolism in the cells of the anterior, posterior corneal epithelium and keratoblasts in any process that violates this metabolism.

In the patent RU 2404768 (publ. 10.03.1999) disclosed eye drops for the prevention and treatment of cataracts, containing, g:

taurine 1.5-1.9 carnosine 1.5-1.9 glutathione not less than 0.01 low molecular weight dextran microdispersed 10.5-15.0 benzalkonium chloride 0.005-0.02 purified water up to 100 ml

A disadvantage of the known preparations containing taurine is the presence of benzalkonium salts, which can cause allergic reactions. Therefore, there is a need for new effective and safe treatments for cataracts.

In the market of ophthalmic preparations of the Russian Federation there are Taulong eye drops (Institute of Pharmaceutical Technologies CJSC) containing 3 wt.% Taurine, and also, g:

nicotinamide (niacin, vitamin PP) four dextran thirty methyl parahydroxybenzoate (methyl paraben, nipagin) one sodium chloride 4,5 potassium monophosphate 10 sodium dibasic phosphate 8.5 water for injections up to 1000 ml

Currently, there are no common ideas about the causes and mechanisms of glaucoma development. Moreover, sometimes difficulties arise when trying to define the concept of “glaucoma”. Experts count about 60 eye diseases, which have the following common features: constant or periodic exceeding of an individually tolerated IOP level, glaucoma optical neuropathy, leading at the final stage to optic atrophy, and visual disturbances characteristic of glaucoma.

In the context of the invention, the term "glaucoma" refers to a chronic eye disease characterized by a constant or periodic increase in intraocular pressure (IOP) with the development of trophic disorders in the outflow pathways of the intraocular fluid, in the retina and in the optic nerve, which causes the development of marginal excavation of the optic disc and the appearance of typical defects in sight.

In Ito Y., Nagai N., Shimomura Y. “Reduction in Intraocular Pressure by the Instillation of Eye Drops Containing Disulfiram Included with 2-Hydroxypropyl-β-cyclodextrin in Rabbit” (Biol. Pharm. Bull. Vol. 33 (9 ) (2010) P.1574-1578, published 08.06.2010) in a model of ocular hypertension in rabbits caused by rapid infusion of a 5% glucose solution, it was shown that the administration of eye drops containing 0.1-0.5% disulfiram, 1.1-5.0% 2-hydroxypropyl-β-cyclodextrin and 0.1% hydroxypropyl methylcellulose in the period from 5 to 30 minutes after the induction of ocular hypertension, allows to reduce IOP by 10-30%. The authors of the article believe that the results give reason to consider the studied drugs as the basis for the development of anti-glaucoma drugs.

In the article by Ermakova V.N. “The effectiveness of the combination of taufon with antiadrenergic drugs in primary open-angle glaucoma” (Ross. Oft. Journal No. 2 (2008). S.12-17) showed that the combined use of taufon with timolol, proxodolol, proxofelin and proxocarpine for a long time ( up to 1 year) can only slightly reduce IOP, but sufficiently improves the outflow of aqueous humor.

Ophthalmic hypertension is not a disease as such, but it is a pathological condition of increased intraocular pressure, which is normally in the range of 10-21 mm Hg. Persistent or frequently occurring ophthalmic hypertension can not only cause glaucoma, but also lead to other eye damage leading to loss of vision, such as retinal vein occlusion and non-glaucomatous destruction of the optic fiber layer [Minckler D.S. "Histology of optic nerve damage in ocular hypertension and early glaucoma." Surv. Ophthalmol. Vol. 33 (April 1989). P.401-411].

In the article Bunin A.Ya., Yartseva E.I., Kolesnikova Yu.A., Ermakova V.N., Yakovleva A.A., Bernikova T.A., Komleva N.A. “The effect of taurine on intraocular pressure and the blood-ophthalmic barrier (experimental study [Issue. Off. No. 1 (1978). P.22-24] on the model of prostaglandin hypertension in rabbits, it was shown that the instillation of a 4% solution of taurine delays the increase in IOP and statistically significantly reduces the IOP of the experimental eye by 2-5 mm Hg throughout the experiment. Similar results were obtained on the model of salt hypertension of the eyes in rhesus monkeys. Thus, taurine has a hypotensive effect on ophthalmotonus, which may be due to but inhibition of secretion of aqueous humor.

However, there is a need for ophthalmic preparations with greater pharmacological activity.

Brief Description of the Drawings

Figure 1 shows the dependence of intraocular pressure (IOP) on time for a model of acute glaucoma in rabbits.

Figure 2 presents the dependence of intraocular pressure (IOP) on time for a model of chronic glaucoma in rabbits.

Description of the invention

The authors of the present invention conducted extensive research and found that it is possible to create a stable liquid pharmaceutical composition containing 0.2-0.5 wt.% Disulfiram. Thus, the present invention, aimed at expanding the arsenal of drugs, provides an ophthalmic preparation in the form of eye drops containing disulfiram and taurine, intended for the treatment of pathological conditions of the eyes selected from cataracts, glaucoma, ophthalmic hypertension and traumatic damage to the cornea, characterized in that it contains 0.2-0.5 wt.% Disulfiram dissolved in a pharmaceutically acceptable water-based carrier due to the formation of an inclusion complex with hydroxypropylcyclo ectrin, present in an amount of 0.5-2.0 wt.%, 2.0-5.0 wt.% taurine, an agent providing the required osmolality, containing sodium chloride, monohydrogen phosphate and phosphate buffer, and methyl paraben (nipagin) as preservative.

The term "treatment" in the context of the invention should be understood in a broad sense, in which it means improving the course of the disease, slowing the progression of the disease, partial or complete restoration of eye function or eliminating the pathological condition, as well as the removal of undesirable consequences caused by the pathological condition.

The method for calculating the composition of an agent providing the required osmolality, depending on the set values of the osmotic pressure and pH of the pharmaceutical composition, is within the competence of an average specialist in this field. The content of preservative (methylparaben) should not exceed the value established by the current standards for local use.

The achievement of the technical result of the invention, which consists in improving the course of cataracts or glaucoma, as well as in the long-term decrease in intraocular pressure, has been demonstrated in appropriate adequate models in vivo.

In a comparative study of the action of the well-known drug “Taufon, eye drops 4%” and the drug in accordance with the invention on a model of traumatic cataract in rabbits, the authors showed that the best results, characterized by minimal area and intensity of turbidity of the damaged area of the lens, were observed in rabbits treated with the proposed drug (table 2).

In a comparative study of the action of the well-known drug "Taufon, eye drops 4%" and the drug in accordance with the invention on the model of acute glaucoma in rabbits, the authors showed that the best results, characterized by a more noticeable decrease in IOP, were observed in rabbits treated with the proposed drug (figure 1 )

In a comparative study of the action of the well-known drug "Taufon, eye drops 4%" and the drug in accordance with the invention on a model of chronic glaucoma in rabbits, the authors showed that the best results, characterized by a significantly greater decrease in IOP, were observed in rabbits receiving the proposed drug (figure 2 )

In the process of conducting all studies, no side effects were found, as well as signs of intolerance and allergic effect of the proposed drug.

Thus, the authors conclusively confirm the achievement of the claimed technical result of the present invention.

The implementation of the invention

The invention will now be illustrated by examples of its implementation.

Example 1. General method for the preparation of eye drops

Separately, a solution of an agent providing the required osmolality is prepared. To do this, in sterile distilled water, taken in a volume of 10% of the volume of the finished product, sodium dihydrogen phosphate and sodium chloride are dissolved with stirring.

In sterile distilled water, taken in a volume of 70% of the volume of the finished product, methyl paraben (nipagin) is dissolved with stirring, disulfiram is added, and then hydroxypropyl cyclodextrin (HCPD). The mixture is stirred in the absence of light until a solution is obtained (approximately 20 hours), after which taurine and a prepared solution of an agent providing the required osmolality are added. Sterilized filtration is carried out through a filter with a pore size of 0.2 μm, aseptically Packed in 10 ml bottles, which are then corked and labeled.

The mass content (in g / 100 g of the solution and in wt.%) Of solid substances in the preparations prepared in accordance with example 1 are presented in table 1.

Table 1 Component Drug 1 Drug 2 Mass g Mass% Mass g Mass% Disulfiram 0.2 0.2 0.5 0.5 GPCD 0.5 0.5 2.0 2.0 Taurine 2.0 2.0 5,0 5,0 Sodium dihydrogen phosphate 0.26 0.26 0.25 0.25 Sodium hydrogen phosphate 0.1 0.1 0.1 0.1 Sodium chloride 0.8 0.8 0.85 0.85 Methylparaben 1,0 1,0 1,0 1,0

Example 2. The study of therapeutic effects on a model of traumatic cataract in rabbits

The study is carried out on 24 rabbits of the breed "Chinchilla" with an average weight of 3.5 kg, age 3.5-4 months with a model of traumatic cataract.

Modeling of traumatic cataract is carried out on the right eye of all animals as follows. After drug myosis caused by double instillations of a 1% solution of pilocarpine hydrochloride in the conjunctival cavity with an interval of 15 minutes, laser coagulation of the pupil pigment rim is performed with localization of coagulates 1.5-2.0 mm outward from the optical center of the lens in the meridian of 8-10 h. 15-40 coagulates are applied to the iris of each eye. Laser radiation parameters: pulse energy 1.6-2.2 W, pulse duration 0.6 sec. Laser radiation was delivered through the head-on binocular ophthalmoscope.

In accordance with the objectives of the study, all animals are divided into 3 groups (table 2).

table 2 Group The drug and dosage regimen The number of animals (eye) one The drug 2 in accordance with the invention; 1 mg / kg rabbit weight 1 time per day subconjunctival for 10 days. 6 (6) 2 “Taufon, eye drops 4%”; 1 mg / kg rabbit weight 1 time per day subconjunctival for 10 days. 6 (6) 3 Water for injection in 0.3 ml rabbit 1 time per day subconjunctival for 10 days. 6 (6)

In the first week, lens biomicroscopy and the study of its transparency are carried out daily, and then weekly in transmitted light using a SchL-2B slit lamp and a head-mounted binocular microscope (HBO-2) using ophthalmoscopic lenses of various optical powers.

In addition, in all rabbits, immediately after cataract modeling, as well as after 1 and 2 months of therapy with the compared drugs, photographic recording of the lens opacity is performed using the Retcam-2 apparatus (manufactured by Massive Research, USA). The results of dynamic observation of rabbits are recorded in a special registration card.

30 minutes after the laser exposure, the pigment border of the pupil in the areas of application of laser coagulates acquires a milky white color. On the second day of the experiment, the pupil gains its previous size and exposes the part of the lens exposed to laser radiation. It represents a site of intense opacification of the capsule and the anterior cortical layers of the horseshoe-shaped crystalline lens (projection of the pigmented border of the narrowed pupil at the time of laser exposure). In this case, a thin area of turbidity, repeating the contour of the edge of the pupil, is surrounded by a halo of subcapsular vacuoles and areas of developing turbidity that do not extend more than 1.5 mm from the main "contour" turbidity.

Starting from the third or fourth day, the clouding of the lens areas under consideration reaches maximum intensity, depth and area and stabilizes. Traumatic cataract acquires a tendency to reverse (extremely insignificant) development starting from the 30th day of the experiment. However, even after 60 days of treatment with the studied drugs, in no case was a complete regression of lens opacity observed.

The area of the lens opacification is determined using a micrometer grid superimposed on a full-sized image of the lens, made using the apparatus "Retcam-2", according to the formula:

S = N + n / 2,

where S is the area of turbidity, mm ² ; N is the number of millimeter squares completely “occupied” by turbidity; n is the number of millimeter squares partially “occupied” by turbidity.

The severity of clouding of the lens is evaluated on a four-point scale: "0" - the full transparency of the lens; "1" - gentle cloudy cloudiness; “2” - pronounced turbidity, behind which, however, a weakened reflex from the fundus is guessed; "3" - intense dense opacification of the lens in the absence of a reflex from the fundus in its projection. Due to the fact that the clouding of the lens is not uniform, the average clouding coefficient is calculated by multiplying the severity of clouding in each of its sections by its area, followed by summing and dividing by the total clouding area.

The results of dynamic observation of rabbits in the groups shown in table 1 are presented in table 3.

Table 3 n Observation stage Group
pa 30 days 60 days Area, mm ² Severity Area, mm ² Severity one 6 5.3 ± 0.5 2.5 ± 0.3 4,5 ± 0,5 2.0 ± 0.2 2 6 5.8 ± 0.5 2.7 ± 0.2 5.0 ± 0.5 2.1 ± 0.2 3 6 6.1 ± 0.6 2.8 ± 0.2 5.8 ± 0.5 2.6 ± 0.2

In the study of the effectiveness of animal therapy, it was found that both studied drugs have a significant positive effect on the clinical course of experimental traumatic cataracts. So, after 1 month of treatment in all animals treated with the compared preparations, there was a steady tendency to a decrease in the area and intensity of lens opacification. Moreover, the changes under consideration relate primarily to the vacuolization zone and “secondary” opacification of the anterior subcapsular and anterior cortical layers of the lens.

According to the results of the examination on the 30th day of the experiment, the preparation according to the invention turned out to be slightly, but statistically significantly more effective than the preparation “Taufon, eye drops 4%”. In control group 3, the area, depth and intensity of turbidity remained more stable than in animals treated with therapy.

According to the results of further observation of rabbits, carried out from the 30th to the 60th day of the experiment, a more noticeable tendency was found to reverse development of pathological changes in the lenses (area, depth and severity of opacification), especially in group 1, treated with the drug in in accordance with the invention.

Example 3. The study of therapeutic effects on the model of acute glaucoma in rabbits

Studies are carried out on rabbits of the breed "Chinchilla" weighing from 1.5 to 2.1 kg Intraocular pressure (IOP) is measured with a TonoVet non-contact automatic tonometer (Jorgen Kruuse, Denmark) and animals with basal IOP of 12-16 mm Hg are selected for further studies, forming 3 groups of 4 individuals of both sexes in each.

A pharmaceutical carrier is administered to the rabbits in the right (control) eye, and the solution of the test drug 2 is injected into the left (test) eye. 15 minutes after the instillation of the drug, 5% dextrose solution (15 ml / kg) is administered to the rabbits in the posterior ear vein. IOP is measured every 5 minutes until a value close to normal is reached. The measurement results averaged by groups are shown in figure 1.

Example 4. The study of therapeutic effects on a model of chronic glaucoma in rabbits

Studies are carried out on rabbits of the breed "Chinchilla" weighing from 1.5 to 2.1 kg Diazepam (1 mg / kg) and ketamine (25 mg / kg) are intravenously administered to animals. A freshly prepared solution of α-chemotrypsin (50 U in 0.1 ml of sterile saline solution) is introduced into the posterior chamber through the cannula. Intraocular pressure (IOP) is measured with a TonoVet non-contact automatic tonometer (Jorgen Kruuse, Denmark) and animals with stable ophthalmic hypertension are selected for further studies, forming 3 groups of 4 individuals of both sexes in each.

A pharmaceutical carrier is administered to rabbits in the right (control) eye and IOP is measured at the starting time point. In the left (experienced) eye - a solution of the studied drug 1. IOP is measured at the initial time, and then - at 15, 30, 45, 60, 120 and 180 days of the experiment. The measurement results, averaged by groups, are shown in figure 2.

Example 5. The study of reparative action on the model of an extensive epithelial defect of the cornea in rabbits

Experimental studies are carried out on 16 male rabbits of the breed "White Giant" (32 eyes) weighing 2.8-3.0 kg, contained in standard vivarium conditions. As an experimental model, a model of an extensive corneal epithelial defect is used, which is applied to both eyes of each animal as follows. After epibulbar anesthesia with innocaine in the center of the cornea by trepan for a layer-by-layer transplantation of the cornea of the eye, wound damage is formed with a diameter of 5 mm and a depth of 0.5 mm, for which the restrictive pin on the trepan is set in the appropriate position. The area of damage is stained with 1% fluorescein sodium salt solution. Removing a non-through disc, including the epithelium, the Bowman’s membrane and the surface layer of the stroma, within the fluorescein mark is made with a special curved spatula. Then the defect is re-stained with the same solution and washed with sterile saline. All manipulations are performed under standard total intravenous anesthesia.

After a standard operation, the animals are divided into two groups of eight individuals in each group. In the postoperative period, the animals of the first group in one eye every day 2-3 drops 2 times a day instill the drug in accordance with the invention, the animals of the second group - comparison drug "Taufon, eye drops 4%". The second eye serves as a control. A sterile saline solution is instilled into the control eyes.

The effectiveness of wound healing is evaluated according to the results of a clinical study of the eye and the time of completion of epithelialization of the area of surgical injury using the following research methods:

1) inspection in focal and side lighting,

2) biomicroscopy of the anterior segment of the eye using a Heine HSL 150 manual slit lamp with an assessment of the condition of the conjunctiva, its vascular injection, the presence of hemorrhages and edema. The state of the cornea is also assessed for the area, nature and depth of the lesion, the presence and nature (diffuse, local) of edema, the degree of corneal infiltration, the presence of superficial and deep vascularization of the cornea, and also determine the nature and type of formed scars.

3) a fluorescein test for staining the cornea, which is performed with sterile disposable strips of fluorescein (manufactured by Haag-Streit AG) to assess the dynamics of corneal epithelization and determine the time of epithelization.

All research data is entered in special report forms and stocked with photographs.

At the final stage, morphological studies of the enucleated eyes of rabbits sacrificed by air embolism are carried out on the 25th day after the start of the experiment. After enucleation, the eyes intended for examination are fixed in a 10% formalin solution and transferred to a certified veterinary pathological and anatomical laboratory.

As a result of studies using methods 1) -3) for the preparation in accordance with the invention and the well-known preparation “Taufon, eye drops 4%”, a generalized estimate is obtained, shown in table 4. To obtain this estimate, we proceeded from all indicators of the cornea, taking into account the experimental and control eyes with the same epithelization.

Table 4 Best eye epithelization: experienced (eyes /%) control (eyes /%) Group 1 (drug 2) 06/24 5 / 62.5% 0 / 0,0% 06/29 5 / 62.5% 1 / 12.5% 06.07 6 / 75.0% 1 / 12.5% Group 2 (Taufon, 4%) 06/24 1 / 12.5% 0 / 0,0% 06/29 3 / 37.5% 2 / 25.0% 07/07 4 / 50.0% 2 / 25.0%

The results of a morphological study of experimental eyes with controls according to the following histological criteria for evaluating wound healing:

1) the degree and presence of corneal edema,

2) the presence of vascularization of the cornea,

3) the presence of fibrosis or pathological granulation of the cornea,

4) the degree of inflammation,

5) the degree of ulceration of the cornea,

6) corneal epithelial hyperplasia

in degrees from normal (0) to severe degree (4) are summarized in table 5.

Table 5 Drug use: Effectively (animal /%) Ineffective (animals /%) Equivalently (animals /%) Group 1 (drug 2) 5 / 62.5% 3 / 37.5% 0 / 0,0% Group 2 (Taufon, 4%) 4 / 50.0% 3 / 37.5% 1 / 12.5%

The data obtained in the examples show the achievement of the claimed technical results in the implementation of the present invention in accordance with the variants of the preparation containing various amounts of active ingredients - a complex formed by disulfiram and cyclodextrin, and taurine.

Claims (6)

1. An ophthalmic preparation in the form of eye drops containing disulfiram and taurine, intended for the treatment of pathological conditions of the eyes selected from cataracts, glaucoma, ophthalmic hypertension and traumatic damage to the cornea, characterized in that it contains 0.2-0.5 wt.% Disulfiram dissolved in a pharmaceutically acceptable carrier based on water due to the formation of an inclusion complex with hydroxypropylcyclodextrin present in an amount of 0.5-2.0 wt.%, 2.0-5.0 wt.% taurine, an agent providing the required osmolal spine, wherein said agent comprises sodium chloride, sodium monohydrogen phosphate and dihydrogen phosphate and methylparaben (Nipagin) as a preservative. 2. The ophthalmic preparation according to claim 1, characterized in that it contains 0.2 wt.% Disulfiram dissolved in a pharmaceutically acceptable carrier based on water due to the formation of an inclusion complex with hydroxypropylcyclodextrin present in an amount of 0.5 wt.%, And 2.0 wt.% Taurine. 3. The ophthalmic preparation according to claim 1, characterized in that it contains 0.5 wt.% Disulfiram dissolved in a pharmaceutically acceptable carrier based on water due to the formation of an inclusion complex with hydroxypropylcyclodextrin present in an amount of 2.0 wt.%, And 5.0 wt.% Taurine. 4. The ophthalmic preparation according to claim 3, characterized in that it is intended for the treatment of cataracts. 5. The ophthalmic preparation according to claim 1-3, characterized in that it is intended for the treatment of glaucoma and / or ophthalmic hypertension. 6. The ophthalmic preparation according to claim 3, characterized in that it is intended for the treatment of traumatic damage to the cornea.

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