RU2298408C2 - Composition for cataract treatment - Google Patents

Abstract

FIELD: medicine, ophthalmology, pharmacy.

SUBSTANCE: invention proposes a composition used in treatment of cataract that contains propolis aqueous extract in the ratio 1:5, 50% polyflower floral honey dissolved in this extract, and 2% of native mother milk. Invention provides stabilization and a definite regression in lens turbidity, reducing activity of lens lipid peroxidation, increasing the content of glutathione reduced form (GSH) and preventing oxidation of reduced protein thiol groups. Also, the composition shows the positive effect on activity of glutathione-dependent enzymes in the antioxidant protection system of lens. Invention provides stabilization and regression of cataract forming.

EFFECT: improved and valuable medicinal properties of composition.

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Description

The invention relates to medicine, namely to pharmacotherapy of eye diseases, and can be used for the conservative treatment of cataracts.

One of the leading points in the etiopathogenesis of cataracts is the pathological activation of free radical oxidation of membrane lipids and other lens biopolymers [1]. The reduced form of glutathione plays an important role in ensuring the transparency of the lens, supporting protein thiol groups in the reduced state [2].

For conservative treatment of cataracts, Oftan Katahrom drops are used. The drug has an antioxidant effect, improves metabolism and trophic tissue of the eye. According to a number of studies, the drug does not have a high anti-cataract effect, but is effective for tissues located in front of the lens [3, 4, 5]. The composition of the drug: cytochrome C - 675 μg, adenosine - 2 mg, nicotinamide - 20 mg, sodium succinate - 1 mg, benzalkonium chloride - 40 μg in 1 ml of the finished drug.

Beekeeping products - royal jelly, honey, propolis - have a high antioxidant and membrane stabilizing activity, a stimulating effect on the metabolic processes of body tissues, have a wide range of biologically active compounds, are non-toxic, and synergistic to a living organism [6]. There is evidence of an increase in the biological effect and stability of the biological properties of these beekeeping products when used together. In particular, complex preparations of honey, royal jelly and propolis (Apitok, Apitonus, Topolek, Apitonik) are used to stimulate metabolic processes, increase nonspecific resistance, expand the adaptive capabilities of the body, in the complex therapy of diseases associated with increased activity of free radical processes of oxidation of biopolymers [6, 7].

In ophthalmic practice, the topical milk product Kolgel (2% aqueous solution) is used locally to improve the reparative processes of the corneal epithelium [7, 8]. Propolis aqueous extract 1: 5 was used in an experiment with a purulent ulcer and a chemical burn of the cornea, while the normalization of the activity of proteolytic enzymes in the corneal tissue was associated with membrane-stabilizing activity [9]. There is no information on the effect on the lens metabolism of these drugs and the possible anti-cataract effect.

There is evidence of a positive effect of topical application of a 50% aqueous solution of honey for age-related cataracts in the initial stages [10]. In the literature there is an indication of the positive results of systemic use of royal jelly in combination with honey for cataracts [11]. However, these studies have an empirical basis; there is no biochemical explanation of the positive results.

Composition of native royal jelly: acetylcholine, free choline, estradiol, progesterone, testosterone, entomological hormones (protractorotropic, molting hormones, tovenile hormones), insulin-like peptides, lysozyme, vitamins (B ₁ , B ₂ , PP, Pantothenic acid, B _{6 12} , folic acid, biotin), organic acids (10-hydroxy-trans-delta-decenoic acid, 9-hydroxy-delta-decenoic, 2-keto-decenicarboxylic, 9-keto-2-decenicarboxylic, 10-oxydecanoic, paraoxybenzoic, lauric, adipic, amber, azelaic, palmitic, stearins aromatic, oleic, linoleic, lipoic and a number of others), carbohydrates (glucose, fructose, ribose, sucrose, maltose, isomaltose, trehalose, neotregalose, turanose, gentiobinose), minerals (potassium, sodium, calcium, magnesium, phosphorus, manganese, copper, zinc) [8, 12].

Composition of flower honey: carbohydrates (fructose, glucose, a small amount of oligosugars), organic acids (malic, lactic, gluconic, succinic, tartaric, citric, oxalic, formic, acetic, butyric), amino acids (proline, phenylalanine, tyrosine, asparaginic, glutamic ), enzymes (diastase, invertase, catalase, peroxidase, o-diphenol oxidase, glucose oxidase), vitamins (B ₂ , PP, C, B ₆ , K, E), minerals and trace elements (copper, iron, manganese, calcium, potassium , sodium, magnesium, zinc, cobalt and others), littides and free fatty acid (palmitic, stearic, oleic, lauric, arachidic, triacylglycerides), lipoids (sterols, phospholipids) gidrooksimetilfurfurol, flavonoids [6, 8].

The composition of the aqueous extract of propolis 1: 5: flavonoids, decenoic acids, phenolic compounds (caffeic, n-coumaric, ferulic acid; scopoletin, esculletin, umbelliphone), terpenes, saponins, ecdysteroids [9].

The purpose of the invention. Development of a local ophthalmic drug of biological origin with high antioxidant properties, the use of which in the experiment will cause stabilization and regression of the developing cataract.

The essence of the invention is that for the treatment of cataracts in the experiment, the composition "apicomposition" was used, containing aqueous extract of propolis 1: 5, 50% solution of polyfler flower honey and 2% solution of native royal jelly, and in the form of instillations into the conjunctival cavity of the eye 4 times in a day.

Estimated result. Obtaining significantly significant anti-cataract and antioxidant (for lens tissue) effects when using the claimed drug in a laboratory model of cataracts.

The inventive preparation was prepared by preparing 200 ml of an aqueous extract of propolis 1: 5 [13], dissolving 100 g of freshly harvested polyfler flower honey in the obtained extract. A final instillation solution was prepared daily by dissolving 100 mg of the native mother liquor in 5.0 ml of a solution of honey in propolis extract. Between instillations, the preparation was stored in a refrigerator at + 2 ° С; immediately before installation, the preparation was warmed to room temperature.

A comparative study of the antioxidant and anti-cataract effectiveness of the claimed composition was carried out on 42 male rabbits with an average weight of 2 kg, breed "Chinchilla". In each treatment group (and the group without treatment) - 12 animals, 3 rabbits (6 eyes) for each term of biochemical studies. Intact group - 6 animals (12 eyes). In all animals (except intact ones), cataract was caused by chemical initiation of free radical oxidation of biopolymers of eye tissues [14]. Control treatments: placebo, Oftan Katahrom. The duration of the experiment is 56 days. Scheme of treatment: 3-fold daily instillation of 2 drops of the drug into the conjunctival cavity of each eye.

The dynamics of the cataract formation process and the effectiveness of the treatment were evaluated by experimental and clinical methods: lateral illumination, transmitted light and biomicroscopy.

To study the activity of free radical oxidation of lipids, the content of malondialdehyde was determined; To assess the state of the lens antioxidant defense, the amount of reduced glutathione, the total antioxidant capacity of the lens tissue (by the duration of the lag phase of accumulation of malondialdehyde in the lens homogenate incubated in the presence of oxygen), the activity of glutathione peroxidase, glutathione reductase, and glutathione-SH transfer were determined. The amount of reduced thiol protein groups was also determined. The animals were removed from the experiment for biochemical studies of the lenses on the 14th, 28th, 42nd and 56th days after the introduction of the cataractogenesis inducer.

In animals of all groups, the initial cataractal changes of the lens appeared by 3–7 days in the cortex and, in the absence of drug treatment, tended to steady progress, with the exception of 1 case of stabilization by 42 days. By 56 days in animals that were not treated, there were drainage foci of opacification of the cortical lens. Drug treatment was started from the time the initial cataract changes of the lenses in all animals appeared (from 7 days after the introduction of the cataractogenesis inducer).

The effect of the claimed composition. Royal jelly therapy turned out to be more effective in terms of the percentage of stabilization and regression of turbidity by 28 days (Table 1).

Table 1.
The dynamics of lens opacities in the treatment of the studied drugs Observation period Turbidity Dynamics Placebo Oftan Katahrom "Apicomposition" 0-14 days progress one hundred% one hundred% one hundred% stabilization - - - regression - - - 14-28 days progress one hundred% one hundred% 72.22% stabilization - - 27.78% regression - - - 28-42 days progress 91.7% 75% 58.33% stabilization 8.3% 25% 25% regression - - 16.67% 42-56 days progress 83% 67% 16.67% stabilization 17% 33% fifty% regression - - 33.33%

The treatment of the claimed composition, in comparison with the control treatment methods, significantly (p <0.05) significantly reduced the activity of free radical oxidation of the lens lipids on days 14, 28 and 42; prevented the oxidation of protein reduced thiol groups on days 14, 28 and 56; increased the content of reduced glutathione on days 14, 28, 42 and 56; more significantly prevented a decrease in the duration of the lag phase of accumulation of malondialdehyde in lens homogenates on days 14, 28, and 56. The use of the “apicomposition” composition shifted the peak of glutathione peroxidase activity from day 7 to day 14, prevented significant depletion (day 28) and contributed to an increase in enzyme activity on days 42 and 56; prevented a significant decrease in the activity of glutathione reductase at all observation times; slightly increased the activity of glutathione-SH-transferase on days 14, 28, 42 and 56. In numerical terms, the results are presented in tables 2, 3, 4 and 5.

Table 2.
Dynamics of MDA content in the lens tissue of experimental animals during treatment with the compared drugs (* - the difference with the Oftan Katahrom treatment series is significant, p <0.05). day of animal withdrawal from the experiment / type of treatment the amount of the test compound (in µmol / g tissue) - 95% CI without treatment placebo Oftan Katahrom "apicomposition" intact 0.0034 (0.0029; 0.0039) 7 day experiment 0.0199 (0.015; 0.0248) 14/7 day experiment / therapy 0,067 (0,056; 0,078) 0.0662 (0.0625; 0.0699) 0.0677 (0.061; 0.0744) 0.024 * (0.0218; 0.0262) 28/21 days of the experiment / therapy 0.0465 (0.0372; 0.0558) 0.04805 (0.04095; 0.05515) 0.0477 (0.0429; 0.0505) 0.0214 * (0.0203; 0.0225) 42/35 day experiment / therapy 0.0568 (0.0418; 0.0718) 0.05738 (0.04928; 0.06548) 0.05609 (0.05339; 0.05879) 0.0169 * (0.0151; 0.0187) 56/49 day experiment / therapy 0.028 (0.0255; 0.0305) 0.02744 (0.02124; 0.03364) 0.0282 (0.0239; 0.0325) 0.0304 (0.0283; 0.0325)

Table 5.
Dynamics of the activity of glutathione-dependent antioxidant enzymes in the lens tissue of experimental animals during treatment with the studied drugs (* - the difference with the Oftan Katachrome treatment series is significant, p <0.05). day of animal breeding indicator / type of treatment the activity of antioxidant enzymes (in units / g of protein) - 95% CI the experiment without treatment placebo Oftan Katahrom "apicomposition" intact G-peroxidase 6.53 (5.16; 7.9) G-reductase 9.4 (7.81; 10.99) G-SH transferase 15.98 (13.6; 18.36) 7 day experiment G-peroxidase 7.51 (4.96; 10.06) G-reductase 5.15 (3.63; 6.67) G-SH transferase 15.81 (14.04; 17.58) 14/7 day experiment / therapy G-peroxidase 5.76 (5.4; 6.12) 5.77 (4.93; 6.61) 5.75 (4.96; 6.54) 6.27 (5.86; 6.68) G-reductase 2.81 (2.36; 3.26) 2.84 (2.59; 3.09) 4.59 (3.81: 5.37) 5.74 (4.1; 7.38) G-SH transferase 6.69 (6.19; 7.19) 6.08 (5.43; 6.73) 7.53 (6.02; 9.04) 15.71 * (11.33.20.09) 28/21 days of the experiment / therapy G-peroxidase 3.14 (2.76; 3.52) 3.21 (3.06; 3.36) 4.54 (4.18; 4.9) 6.03 * (5.54; 6.52) G-reductase 1.54 (1.24; 1.84) 1.74 (1.48; 2) 1.54 (1.34; 1.74) 3.44 * (2.93; 3.95) G-SH transferase 5.3 (4.87; 5.73) 5 (4.17; 5.83) 5.21 (4.47; 5.95) 13.36 * (8.33; 18.39) 42/35 day experiment / therapy G-peroxidase 3.14 (2.51; 3.77) 2.94 (2.88; 3) 4 (3.71; 4.29) 6.46 * (5.95; 6.97) G-reductase 1.32 (1.08; 1.56) 1.17 (1.01; 1.33) 0.92 (0.82; 1.02) 3.2 * (2.16; 4.24) G-SH transferase 4.26 (3.55; 4.97) 4.5 (3.89, 5.11) 4.14 (3.73; 4.55) 17.29 * (12.8; 21.78) 56/49 day experiment / therapy G-peroxidase 1.53 (1.37; 1.69) 1.85 (1.59; 2.11) 2.89 (2.53; 3.25) 7.57 * (6.71; 8.43) G-reductase 1.27 (1.07; 1.47) 1.06 (0.92; 1.2) 1.01 (0.78; 1.24) 4.03 * (2.7; 5.36) G-SH transferase 2.82 (2.31; 3.33) 2.71 (2.05; 3.37) 2.63 (1.86; 3.41) 19.21 * (15.35; 23.07)

Information sources

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Claims (1)

Composition for the treatment of cataracts based on polyfler flower honey, characterized in that it additionally contains an aqueous extract of propolis 1: 5, 2% native royal jelly, and the content of polyfler flower honey is 50% solution.