RU2414218C1 - Eye drops for treatment of dystrophic diseases and traumas of eyes - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to ophthalmology, and can be applied as reparative and regenerative ophthalmological medication. Eye drops represent combined medication based on taurine and polymer of dextran or copolymer N-vinylpyrrolidone with 2-methyl-5-vinylpyridine, which contains nicotinamide, nipagin, sodium chloride, potassium monophosphate, sodium diatomic phosphate and water with definite component ratio, for treatment of dystrophic diseases and traumas of eye tissues: stimulator of reparative processes in case of senile, diabetic, radial and traumatic cataracts; in prevention and treatment of cornea lesions; treatment of hereditary cornea dystrophy.

EFFECT: invention ensures increase of medication efficiency and reduction of instillation quantity.

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Description

The invention relates to the field of medicine, namely ophthalmology, and can be used as a means for the treatment of dystrophic diseases and injuries of ocular tissues: a stimulator of reparative processes in senile, diabetic, radiation and traumatic cataracts; in the prevention and treatment of corneal injuries; treatment of hereditary and acquired retinal dystrophy.

The biogenic compound taurine is known, which is found in high concentrations in the tissues of the retina and lens and is one of the end products of the metabolism of sulfur-containing acids (cysteine, methionine, glutathione, cystine), is directly involved in the conduction of a nerve impulse and in the regulation of metabolic processes - energy, protein and carbohydrate metabolism, osmoregulation. A characteristic feature of taurine is the ability to stimulate reparative processes in dystrophic lesions of the eye tissue.

The following taurine-based eye drops are known in the art: Taufon and Citarin.

The most widely recognized drops are “Taufon”, which are used for dystrophic (associated with malnutrition of tissue) lesions of the retina, including hereditary tapetoretinal degeneration, dystrophy and damage to the cornea, senile, diabetic, traumatic and radiation cataracts, as well as a tool stabilization of the electrolyte composition of the cytoplasm, stimulation of recovery processes in injuries.

The disadvantage of Taufon, as well as many other mono-preparations of eye drops, is their rather short therapeutic effect, which leads to the need to instill drops 4-6 times a day.

In this regard, a tendency has arisen to create combined agents in order to eliminate side effects to expand the therapeutic effect and prolong the therapeutic effect. One of these drugs is Citarin eye drops, which contain in addition to taurine vitamin B ₁₂ and a polymer that prolongs the action of the drug.

The difference of this invention from the drug "Citarin" is the percentage of the main active substance of taurine, polymer, the presence of vitamin PP (B ₃ ), sodium chloride, potassium monophosphate and dibasic sodium phosphate.

The objective of the invention is the creation of domestic eye drops in the form of a combined preparation that has a reparative effect for the treatment of dystrophic diseases and injuries of ocular tissues, which increases the effectiveness of taurine due to the components included in the preparation and prolongs the contact of the drug with the cornea to reduce the number of instillations.

The result of the task are eye drops of the following composition:

Taurine 20-40 g Dextran or copolymer N-vinylpyrrolidone with 2-methyl-5-vinylpyridine 30-100 g Methyl Parahydroxybenzoate (Nipagin) 1 g Nicotinic acid (niacin, vitamin PP) 4 g Sodium chloride 4,5 g Potassium monophosphate 10 g Sodium Dibasic Phosphate 8.5 g Purified water up to 1000 ml

In the proposed composition, the concentration of taurine is taken in the range from 2 to 4% based on the fact that the substance is most active in it: a 2% solution is ineffective, and conglomerates with a polymer form in a solution of more than 4%, which makes it difficult for taurine to penetrate through the cornea and release polymer.

To prolong the contact of the drug with the cornea and reduce the number of instillations, a polymer prolonging substance was introduced — a low molecular weight dextran with a relative molecular weight of 30000-40000 dl or a copolymer of N-vinylpyrrolidone with 2-methyl-5-vinylpyridine (hereinafter referred to as the copolymer) with a molecular weight of 29000 -40000 dl. Dextran is a hydrophilic polysaccharide that slowly penetrates through the vascular walls and, when introduced into the bloodstream, circulates for a long time in it, thus increasing the effectiveness of the ophthalmic preparation, prolonging the therapeutic effect. The copolymer also prolongs the effect of the drug, and also has an immunomodulatory effect. The polymers were taken in the range from 3% to 10%: a less than 3% polymer solution does not have prolonging properties, and a polymer in a concentration of more than 10% forms viscous solutions and gels, which is not suitable for the preparation by physicochemical parameters.

To increase the effectiveness and complex activity of the drug, nicotinamide was introduced into the composition, which is vitamin PP (B ₃ ) and has a vasodilating, hypolipidemic and hypocholesterolemic effect.

Nipagin was introduced into the ophthalmic agent as a preservative and stabilizer, contributing to the preservation of the sterility of the agent, as well as after its dissolution and preparation of drops in the process of their use.

Potassium monophosphate and sodium dibasic phosphate play the role of a buffer solution, with the help of which pH and ionic strength are acceptable for eye drops.

Examples of the preparation of two compositions according to this invention.

The drug is obtained by mixing and dissolving the components in purified water. Sterility of the drug is achieved by sterilizing filtration through membrane filters with a pore diameter of 0.2 μm.

Example composition No. 1:

Taurine 30 g Dextran 30 g Methyl Parahydroxybenzoate (Nipagin) 1 g A nicotinic acid 4 g Sodium chloride 4,5 g Potassium monophosphate 10 g Sodium Dibasic Phosphate 8.5 g Purified water up to 1000 ml

Example composition No. 2:

Taurine 40 g

Copolymer 80 g Methyl Parahydroxybenzoate (Nipagin) 1 g A nicotinic acid 4 g Sodium chloride 4,5 g Potassium monophosphate 10 g Sodium Dibasic Phosphate 8.5 g Purified water up to 1000 ml

In appearance, the proposed drops are a clear, colorless liquid.

The technical result is confirmed by the following examples.

Example 1. Treatment of cataracts.

The experiment was performed on mice of both sexes of the F1 line (CBA × C57B1) weighing 16-18 g. Cataracts were induced by irradiation of mice with ¹³⁷ Cs gamma radiation at a dose of 4.0 Gy (the most appropriate model for senile cataracts). 18 weeks after radiation exposure to one group of animals - in the amount of 92, prophylactic instillation of a new drug was carried out for 7 weeks twice a day, 2 drops in both eyes. The second group of animals in the amount of 60 served as a control; the third group of animals in an amount of 60 was treated with taufon (4% solution of 2-aminoethanesulfonic acid).

At the end of instillation, the animals were examined with an electrophthalmoscope and a magnifier of +15.0 D. It was found that in the treated animals the lens opacity was 46.8% (p <0.01), while in untreated animals it was 74%, in the third group - 64.3%.

Example 2. The treatment of damage to the cornea.

The experiments were conducted on mice of the F1 line. Mice were irradiated with protons with an energy of 9 GeV, a dose rate of 0.05 Gy / s, at a dose of 0.25 Gy. As a test for corneal damage, the incidence of aberrant mitoses 24, 72, 168 and 240 hours after irradiation was studied. A new drug was instilled 2-3 drops in both eyes 5 times every 10 minutes immediately after irradiation. The course was repeated daily for 10 days. The treatment results are presented in table 1.

Table 1
Changes in the frequency of aberrant mitosis in mouse corneal epithelial cells after irradiation with 9 GeV protons Dose, Gy Time investigated, hours Aberrant mitoses,% Without treatment Medicine R 2.5 24 62.5 ± 0.8 59.6 ± 1.1 ≤0.001 72 44.3 ± 1.9 25.0 ± 1.0 ≤0.001 168 28.3 ± 1.2 12.0 ± 0.7 ≤0.001 240 16.8 ± 1.6 2.9 ± 0.5 ≤0.001

The results allow us to conclude that the new drug leads to a partial reliable repair of corneal lesions according to the test for reducing aberrant mitoses.

Example 3. Prevention and treatment of damage to the corneal epithelium.

The experimental conditions are the same as in example 2. Irradiation of mice was carried out in doses from 1.0 to 7.0 Gy. As a test for corneal damage, the incidence of aberrant mitoses was examined 24 and 72 hours after irradiation.

The drug was instilled before irradiation for an hour 5 times and then immediately after irradiation.

The results of the preventive and therapeutic use of the drug are presented in table 2.

table 2
Changes in the frequency of aberrant mitosis in mouse corneal epithelial cells irradiated with 9 GeV protons Dose. Gr. Abberrant mitoses,% Without treatment Treatment R Without treatment Treatment R 24 hours 72 hours 1,0 42.4 ± 0.6 28.5 ± 0.8 ≤0.001 29.5 ± 1.7 17.4 ± 1.2 ≤0.001 2.5 63.0 ± 0.9 47.5 ± 1.2 ≤0.001 43.4 ± 1.9 25.0 ± 1.0 ≤0.001 5,0 80.0 ± 1.2 59.6 ± 1.1 ≤0.001 80.9 ± 2.1 52.9 + 1.9 ≤0.001 7.0 94.6 ± 1.6 70.8 ± 2.0 ≤0.001 85.3 ± 2.5 59.3 ± 1.7 ≤0.001

Thus, the protective and therapeutic property of the proposed drug was revealed, the use of which led to reliable efficacy in the treatment of damaged corneas.

Example 4. Treatment of corneal injuries.

The experiments were carried out on 7 rabbits of the breed "Chinchilla", weighing 2-2.5 kg The technique was as follows: after epibulbar anesthesia with trepan 6.0 mm in diameter, the anterior layers of the corneal stroma were incised, after which this layer was removed along with the epithelium under the level of the incision edge. This technique made it possible to monitor not only the rate of epithelization, but also the regeneration of corneal stroma. The drug was instilled 3 times in the right eye, the left eye served as a control - saline was instilled into it.

The following results were obtained: postoperative inflammatory reaction took place in the experimental group 38 hours earlier than in the control group; plaque on the defect resolved 29 hours earlier, complete epithelialization of the wound occurred 17 hours earlier in the experimental group, stromal edema disappeared 91 hours earlier, and the defect was filled with tissue 31 hours earlier in the experimental group compared to the control group.

We conclude that the drug contributes to a faster resorption of the fibrin film and edema, accelerates the regeneration of the cornea.

Example 5. The treatment of hereditary retinal dystrophy.

Six rats of the F ₁ strain with hereditary retinal dystrophy were injected with a drug solution immediately after birth during the first day. Morphometry of the foci of membranogenesis was carried out with 200 fields of view from 3 blocks; a total of 7200 fields of view of the electron microscope with a magnification of 14000x were studied.

Table 3
The results of the treatment of hereditary dystrophy Stimulation indicators Morphometry data Experienced group Control group + 13.4 ± 42.1 13.5 ± 4.6 ++ 0.32 ± 0.12 0,0 ± 0,0 +++ 0.00 ± 0.00 0,0 ± 0,0

A stimulation surge was detected in the 2 ++ experimental group, equal to 0.32 ± 0.12%, while it was absent in the control.

Thus, the proposed composition of eye drops corresponds to the task and can be used as a tool for the treatment of dystrophic diseases and injuries of eye tissues, a stimulator of reparative processes in senile, diabetic, radiation and traumatic cataracts, in the prevention and treatment of corneal injuries, in the treatment of hereditary and acquired retinal dystrophy.

Claims (1)

Eye drops for the treatment of dystrophic diseases and injuries of ocular tissues based on the biogenic compound taurine, characterized in that they contain a dextran polymer or a copolymer of N-vinylpyrrolidone with 2-methyl-5-vinylpyridine, vitamin B ₃ , sodium chloride, potassium monophosphate, sodium dibasic phosphate water for injection taken in the following amounts per 1000 ml:
Taurine 20-40 g Dextran or N-vinylpyrrolidone copolymer with 2-methyl-5-vinylpyridine 30-100 g Methyl Parahydroxybenzoate (Nipagin) 1 g Nicotinic acid (niacin, vitamin PP) 4 g Sodium chloride 4,5 g Potassium monophosphate 10 g Sodium Dibasic Phosphate 8.5 g Water for injections up to 1000 ml