RU2004234C1 - Composition stimulating epithelium regeneration - Google Patents

Abstract

The invention relates to medicine and relates to a composition for treating skin atrophy caused by prolonged use of corticosteroids, preventing skin aging and wrinkles, and eliminating the symptoms of certain dermatological diseases. The preparation is made in the form of an ointment containing fat-soluble vitamins A E, D and is an ointment based on water-emulsion, stimulating the reparative and physiological regeneration of the skin, which contains the active components in the form of retinol palmitate, tocopherol acetate, ergocalciferol, in as a fat base - liquid paraffin, as an emulsifier - N1 emulsifier. as well as antioxidants in the following ratio of components wt.%: Retinol palmitate - 0.5 - 1.0 Tocopherol acetate - 0.1 - 0.5 Ergocalciferol - 0.001 - 0.005 Antioxidants - 0.2 emulsifier N1 - 7.0-10 0 Vaseline oil - 7.0 - 10.0 Glycerin - 10.0 Ethyl alcohol 96% - 10.0 Distilled water to 100.0.

Description

The invention relates to medicine, and relates to the creation of a composition for treating skin atrophy caused by prolonged use of corticosteroids, preventing skin aging and wrinkles, eliminating the symptoms of certain dermatological diseases, e.g. neurodermatitis, hair growth and increasing skin resistance to damaging environmental factors.

Retinoids are known to be compounds that effectively stimulate the reparative and physiological regeneration of skin cells. The effect of retinoids on the atrophied due to the use of glucocorticosteroid ma-, epidermis was investigated. Tissue regeneration under the influence of fully trans-retinoic acid was twice as intense as without the influence of retinoid. However, the use of fully trans-retinoic acid is impractical due to its high toxicity and strong local irritant effect,

 Another well-known drug leads to the reverse development of aging phenomena, smoothing wrinkles, and enhancing skin resistance to sun damage. The composition is less toxic than that given in the patent.

A disadvantage of this preparation is that 13-cis retinoic acid is used as the active compound, which, although less toxic than fully transretinoic acid, is also capable of causing unwanted side effects.

Preparations containing a mixture of fat-soluble vitamins A, E, D are less toxic than preparations based on isomeric retinoic acids and, at the same time, promote the reactivation of damaged skin cells, improve the cosmetic condition of the skin, and help soften old scars.

The closest in technical essence to the claimed preparation is the preparation indicated in the source. A known preparation is an oil-based ointment containing vitamins A, E, D, which, firstly, helps restore skin cells that are damaged mechanically or by high temperature, and secondly, improves hair growth.

The disadvantage of this preparation is the unreasonably high content of vitamins E and D. An excess of vitamin E can adversely affect the state of the developing and dying germinal system in children and the elderly. Cro0

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in addition, its excess may undesirably affect the resistance of vitamin A. High doses of vitamin D are even more dangerous. Vitamin D can disrupt calcium metabolism, enhance the process of stone formation in the kidneys and liver. In addition, in the patent indicated in the source, vitamin A is not used in the form of retinyl palmitate, while this form is most suitable for external preparations, and also in the patent there are no indications of TOi that the preparation is made on a water-based basis. most suitable for creating preparations containing fat soluble vitamins.

The proposed technical solution makes it possible to create an effective, low-toxic drug for external use based on the fat-soluble vitamins A, E, D, stimulating the reparative and physiological regeneration of the epidermis. The preparation is an ointment based on water and emulsion, which contains the active components in the form of retinol palmitate, tocopherol acetate, ergocalciferol, as a base - liquid paraffin, emulsifier M 1 as an emulsifier, ethyl alcohol and antioxidants in the following ratio of components, wt.%

Retinol palmitate 0.5-1.0 "Tocopherol acetate 0.1-0.5

Ergocalciferol 0.001-0.005

Antioxidants 0.2

Emulsifier No. 1 7.0-10.0

Vaseline oil .7.0-10.0 Glycerin 10.0

Ethyl alcohol 96%, 10.0 Water distilled to 100.0 The claimed drug is highly effective in treating the above conditions due to the combined action of three dermatotropic fat-soluble vitamins: Vitamin A increases cell proliferation in the epidermis, inhibits keratinization, enhances immune responses; vitamin D also has a positive effect on the immune system and promotes rejuvenation of the connective tissue of the skin; Vitamin E enhances the protective properties of the skin, has an antioxidant effect.

The study showed that the inventive preparation (Table 1, Examples 1-3) compared with other ointments (Examples 5-7) most effectively enhances the reparative regeneration of the atrophied epidermis (Table 2). Skin atrophy was caused by treating it with hydrocortisone ointment.

The study was conducted on Bal mice with / s, males weighing 16-18 g, which were cut the skin of the interscapular region of the back on an area of 2-3 square meters. see 0.2-0.3 g of 10% hydrocortisone ointment was applied daily to such areas for 15 days. Starting from the 16th day of the experiment, 0.2-0.3 g of the tested ointments were applied to the animals on the skin treated with hydrocortisone (Table 1, examples 1-3, 5-7). On day 25 of the experiment, the mice were killed by chloroform. The skin was fixed in a mixture of formalin, ethanol and glacial acetic acid in a ratio of 9: 3: 1, paraffin sections were stained with routine dyes, and the epidermis thickness was determined using an ocular micrometer. The thickness of zyperis intact animals was taken as 100%. The results of the study are presented in table. 2

h The ointment of the claimed composition (table. t, examples 1-3) most effectively stimulated the restoration of the epithelial-cellular layer of the skin, while there were no signs of toxicity of the drug. . Ointments with 13-cis-retinoic acid (examples 5-7) enhanced the reparative regeneration of the atrophied epidermis. The effect is dose dependent. However, with an increase in the content of the ointment of the substance, general toxicity also increased; the mice receiving the maximum amount of 13-cis-retinoic acid (Table 1, Example 7) were voluminous, inactive, stunted, their skin rubbed with hair in areas of the nose, covering.

The claimed composition is characterized in that vitamin A is used as retinol palmitate. Vitamin A palmitate is a naturally biologically active form of Vitamin A. This compound has the lowest rates of acute and chronic toxicity. It easily penetrates natural barriers (mucous membrane of the small intestine, skin, etc.), and is easily recognized by transport complexes in both blood and tissues.

Pharmacokinetic studies have shown that the use of vitamin E acetate together with vitamin A palmitate greatly increases the bioavailability of the latter. As the table shows. 3, the bioavailability of vitamin A palmitate in an ointment of the claimed composition is higher than the bioavailability of vitamin A when administered orally and in an ointment containing dimethyl sulfoxide (Table 1, Example 9), although it is known that the presence of dimethyl sulfoxide significantly increases the bioavailability of vitamin AND.

The doses of vitamins A and E used by the ointment are the most effective. The studies (Table 4) showed that thermal and chemical wounds heal faster with an ointment (Table 1, examples 1-3) of the claimed composition than with an ointment containing higher doses of vitamins A and E (table. 1, example 4). Tab. 5-10 shows that the use of the claimed ointment does not cause disturbances in mineral metabolism.

The water-emulsion base on which the ointment is prepared provides easy and quick penetration of the substance through the skin (Table 3). In addition, it is a fact that lipophilic vitamins inside the emulsion droplet provide additional protection for the unstable vitamins from being destroyed by atmospheric oxygen.

As an emulsifier, Emulsifier No. 1 is used (manufacturer - Nizhny Novgorod HFZ), which is

5, a mixture of opposite surfactants: the sodium salts of the sulfate esters of high molecular weight alcohols are m / v type emulsifier, and the high molecular weight s, 1 m / v type emulsifier emulsifier. When used together, the stabilizing effect is significantly higher compared to the use of each emulsifier separately, which guarantees a high physical and chemical

5 drug resistance. The use of emulsifier No. G avoids the use of expensive and inaccessible cetyl and stearyl alcohols, the production of which is not established in

0 to our country and they need to be acquired abroad.

In addition, the ointment contains glycerin to provide a softening effect on the skin and reduce the drying speed of the ointment

5 when applied. Ethyl alcohol provides protection against microbial contamination.

An ointment with fat soluble vitamins is prepared as follows: fat soluble vitamins and antioxidants are mixed with a portion of liquid paraffin and injected into the melt of emulsifier and liquid paraffin. While heating the mixture to 60 ° C and stirring, gradually added in portions to

5 water heated to 60 ° C. After cooling to room temperature, ethyl alcohol and glycerin were added.

Example 1.10 g of retinol palmitate, 5 g of tocopherol acetate, 10 ml of a 05% solution of ergocalciferol in oil 2 g

the antioxidants are ground in a mortar with 50 g of liquid paraffin. The resulting suspension is transferred to the melt 100 g of emulsifier No. 1 and 50 g of liquid paraffin, heated to 60 ° C. After thoroughly mixing the resulting mixture with stirring at a temperature of 60 ° C, 573 g of distilled water are added in small portions. The mixture was cooled to room temperature, 100 g of glycerol and 100 g of 95% ethanol were added, mixed thoroughly and packaged.

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Examples 2-9 Conducted similarly to measure 1, the composition of the ointments are presented in table 1

Thus, a highly effective low-toxicity broad-spectrum preparation has been created on the basis of inexpensive available domestic raw materials, which will find application in dermatological practice for the treatment of various diseases.

(56) German Patent No. 3800972.cl, A61 K 31/59, 1989.

The composition of the ointment

Table 1

the effect of ointments on the thickness of the epidermis of atrophied skin Mice Ba 1b / s, males, 25 days. experience p-8

) An ointment containing hydrocortisone.

) No. of the example (the composition of the ointment is indicated in Table t) under the corresponding number.

The dynamics of the content of retinol palmitaga in blood plasma when exposed to ointments of various compositions

The effect of ointment on reparative skin regeneration

Table

Table 3

Table 4

The effect of the ointment (table. 1, example 1) on the concentration of calcium, inorganic phosphorus and the activity of alkaline phosphatase in the serum of Wistar rats, day 21 of the experiment,, M ± m

Claims (1)

The claims COMPOSITION STIMULATING EPITELIUM REGENERATION, containing vitamins A, E, D, a fatty base, an emulsifier and antioxidants, characterized in that. that it contains active components in the form of retinol palmitate, tocopherol acetate, ergocalciferol, as a base vaseline oil, emulsifier N 1, and ethyl alcohol in the following ratio of components, wt.%: Table 5 Oh yeah 0.5-1.0 0.1-0.5 0.001 - 0.005 0.2 7.0-10.0 7.0-10.0 10.0 10.0 Up to 100