RU2004239C1 - Preparation for healing bacterially contaminated wounds - Google Patents

Abstract

The invention relates to medicine, namely to a wound healing preparation containing retinol palmitate and methyluracil The essence of the invention is as follows. that the wound healing preparation contains retinol palmitate as active ingredients. methyluracil and dimethyl sulfoxide as an emulsifier is a mixture of surfactants under the conditional name Emulsifier N1, as stabilizers are a mixture of butyloxytoluene and butyloxyanisole, a fatty base, glycerin, ethanol 96 ° deg; and water in the following ratio of components, wt.% retinol palmitate 1.0, methyluracil 3.0, dimethyl sulfoxide 10.0, butyloxytoluene 0.1 butipoxy anisole 0.1, emulsifier N1 10.0, liquid paraffin 10.0, glycerin 10.0 ethyl sgmrt 96 ° 10.0 distilled water to 100.0.

Description

The invention relates to medicine and can be used in pharmacy, in asthenia, in the manufacture of medicines.

Compositions are known containing vi- 5 amine A pzlmitate and a fat base, for example, the Avibon preparation of the company herapllx. This composition of the ointment does not provide rapid absorption of vitamin A,

Unstable to oxygen oxidation of air, retinol valmate is destroyed without penetrating the skin, which makes it ineffective.

The most promising wound healing compositions are ointments 15 prepared on an aqueous emulsion basis. Such a base promotes the rapid absorption of the active substance. In addition, in the emulsion, vitamin A is concentrated inside the oil droplets, owing to which 20 it is less susceptible to the destructive action of atmospheric oxygen.

The closest in technological essence and the achieved positive effect to the claimed invention is - 25 is the composition described in Swiss patent 2, which is an oil-in-water emulsion. Vaseline and liquid paraffin are used as the fat base, and ceti-1–30 molar and stearyl alcohols, tween-80 and monostearate are used as emulsifiers.

A disadvantage of this preparation is a weak effect on the regeneration processes in the skin wound. Known ointment can be successfully used o5 for the treatment of only shallow ones: wounds affecting the epidermis and the upper (papillary) layer of the dermis and is ineffective in treating deep and extensive wounds. The ointment contains emulsifiers: 40 cetyl and stearyl alcohols, which are pure, specially cleaned compounds that are very expensive and inaccessible.

The claimed composition is 45 a highly effective and stable preparation intended for stimulating the healing of wounds of various origins (technical result), it includes affordable, economically viable domestic raw materials.

Achieving the goal is that the wound healing preparation contains retinol palmitate, a fat base, antioxidants and emulsifiers. The active components of 55 are palmitate t retinol, methyluracil, dimethyl sulfoxid, and the emulsifier is a mixture of surfactants manufactured by the Nizhny Novgorod Chemical and Pharmaceutical

by the plant under the special name Emulsifier No. G, butyloxytoluene and butyloxyanisole as stabilizers, and liquid paraffin as a fatty base. In addition, the composition contains ethyl alcohol and glycerin in the following ratio, wt.%: Retinol palmitate 1.0 Methyluracil 3.0

Dimethyl sulfoxide 10.0 Butyloxytoluene 0.1

. Butyloxyanisole 0.1

Emulsifier No. 110.0

Vaseline oil 10.0 Glycerin 10.0

Ethyl alcohol 96 ° 10.0 Distilled water to 100.0 The effect of the ointment consists of two effects; methyluracil is a precursor to various types of RNA, which makes it a building material for regeneration processes. Dimethyl sulfoxide promotes better penetration of methyluracil through the skin, increases its bioavailability (table. 3). Retinol palmitate stimulates local epithelial-mesenchymal relationships, activates the function of young fibroblasts, and enhances epithelial proliferation. As a result, the ointment enhances the rearative regeneration in the skin wound.

Tab. 2 shows the healing of various types of wounds under the influence of ointments of various compositions.

The experiments were performed on female Wistar rats weighing 180 ± 10 g. To obtain surgical p, rats under hexenal anesthesia in the interscapular region of the back were removed with the hypodermis in a 2x2 cm area. The wounds were fixed to an aluminum frame. To obtain thermal wounds in rats under hexenal anesthesia, a burn was caused in the interscapular region of the back. A copper cube with an area of one side of 4 cm was used for this. The cube was heated in boiling water for 5 min and applied to the skin surface for 10 s. To obtain chemical wounds to rats under hexenal anesthesia, 0.5 ml of glacial acetic acid was applied and evenly distributed on clipped areas of the skin. For treatment, 0.5 g of ointment was applied daily to the wound once a day. On day 8, the area of the remaining unhealed wound surface was determined and the percentage of healing was calculated. In order to determine the proliferative activity of the epidermis, ZN-thymidine was administered intraperitoneally the animals the day before. Rats were killed by chloroform. The skin was fixed in a mixture of FSUs, histological sections and autographs were stained and treated with routine dyes and reagents. In the preparations, the proliferative activity of the epidermis (tagging index), the thickness of its layers and the cell density of the granulation layer of the dermis were taken into account.

The data table. 2 show that under the influence of ointments containing retinol palmitate, methyluracil and dimethyl sulfoxide (examples 1, 4), healing is much faster than under the influence of ointments containing only retinol palmitate (example 3) or only methyluracil ( Example 2) or retinol palmitate with methyluracil (Example 6) or with dimethyl sulfoxide (Example 7).

Absorption of vitamin A, as shown in table. 3 also occurs much faster if the ointment contains, in addition to retinol palmitate, methyluracil and dimethyl sulfoxide (examples 1, 4, 5). Even with the oral administration of an oil solution of vitamin A, the accumulation of retinol palmitate in blood plasma is slower and does not reach such high rates as when using an ointment of the claimed composition.

The optimal amount of methyluracil-3 wt.%, A decrease in the amount of methyluracil leads to a decrease in the bioavailability of palmitate retinol and to a decrease in the wound healing efficiency (Example 5, Table 2.3). A methyluracil content of more than 3% by weight is not practical since it does not increase the bioavailability and wound healing efficiency (Example 4, Tables 2, 3).

Domestic emulsifier No. 1 is a mixture of surfactants of the opposite type of action: sodium salts of sulfate esters of high molecular weight alcohols, which are emulsifiers of the mass / io type in water and high molecular weight alcohols - emulsifiers of the water in oil type. With their combined use, the necessary stability of the emulsion is achieved no lower than with the use of cetyl and stegryl alcohols.

Butyloxytoluene and butyloxy anisole are used as one hundred vitamin A enhancers.

The use of only one stabilizer does not ensure the stability of vitamin A (examples 9, 10, table. 4); when the stabilizer content is less than 0.1 May%, the stability of the ointment also decreases. The upper limit of the stabilizer value is limited by the requirements of the pharmaceutical committee.

To prevent microbial contamination, 96 ° ethanol is used at a concentration of 10% by weight.

Glycerin was added in an amount of 10% by weight to provide a skin softening effect and to reduce the drying speed of the ointment when applied to the skin.

An ointment with retinol palmitate and methyluracil is prepared as follows: Vitamin A palmitate and antioxidants are triturated with part of the liquid paraffin at room temperature. The resulting slurry is mixed with the melt of the emulsifier and remaining vaseline oil at a temperature of 60 ° C, then distilled water heated to 60 ° C is added in small portions with stirring and heating to 60 ° C to the resulting mass. After cooling the ointment to room temperature, glycerin, ethyl alcohol and a solution of methyluracil in dimethylsulfoxide are added, mixed thoroughly and packaged in aluminum tubes.

The invention is illustrated by the following examples.

Example 1.10 g of palmitate retinol, 1 g of butyloxytoluene and 1 g of butyloxyanisole are triturated in a mortar with 30 g of liquid paraffin at room temperature. In a boiler of an ointment machine, 100 g of an emulsifier and 70 g of liquid paraffin are heated to 60 ° C and, with stirring, the prepared suspension of active substances and antioxidants in liquid paraffin is introduced into the melt obtained. Then, while continuing to soak, 458 g of cooling water heated to 60 ° C are added in a small portion of m to the mixer, glycerin (100 g), ethyl alcohol 96% (100 g and a solution of 30 g of methyluracil in 100 g of dimetofuf- seeded, mix thoroughly and rMi packaged in aluminum tubes.

Examples 2-10 are carried out aythlogically to example 1. The composition and properties of the prepared oils are given in table. -3-4

The invention makes it possible to organize a cost-effective production of a highly effective wound healing preparation based on domestic raw materials. The drug can find application in surgical, oncological and dermatological practice.

(56) U.S. Patent No. 3,943,028 g A with K 31/20 01/20/76.

Switzerland patent No. 670951 p A 61 K 7 / 48.31.07.89.

Table 1

The composition of the ointment

The effect of ointments on wound healing

Example number (tab. 1)

Wound size cm

Surgical wound healing

0.7 x 0.8

0.2 x 0.3 healing

0.2x0.1

0.2 x 0.3

0.2x0.3

Table

Wound size cm

Wound size cm

burn wounds healing

0.6 x 0.8

 0.3 x 0.3

healing

0.2 x 0.2

0.3 x 0.2

0.3 x 0.2

Surgical wounds 0.2 x 0.2 0.7 x 0.6 0.6 x 0.5 0.2 x 0.2 0.4 x 0.5 0.6 x 0.5 0.6 x 0.6

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

Shelf life of ointments

) The time during which at least 95% of the initial amount of palmitate retinol is stored in the ointment under storage conditions at a temperature of +2 - + 4 ° C.

Claims (1)

The claims A DRUG FOR HEALING OF BACTERIALLY CONTAMINATED RAS, containing retinolapalmitate, a water-emulsion base, antioxidants and emulsifiers, characterized in that it contains an emulsifier N1 as an emulsifier, butyl oxitoluene and butyloisinoyl anisole azinoisole stabilizers as stabilizers oil and water and additionally contains methyluracil and dimethyl sulfoxide as well as alcohol as active components Table 3 Table 4 ethyl 96 and glycerin in the following ratio of components, wt.%. Retinol palmitate Methyluracil Dimethylsulfoxid Buty l xytol o l. Butyloxyanisole Emulsifier N1 Vaseline oil Glycerin Ethyl alcohol 96 Distilled water 1.0 3.0 10.0 0.1 0.1 10.0 10.0 10.0 10.0 Up to 100.0