RU2129002C1 - Composition for treatment of wounds, burns, allergic contact dermatitis - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: invention proposes a composition for treatment of wounds, burns, contact and allergic dermatitis that has, wt.-%: product of microbiological synthesis containing γ-linolenic acid 0.1-20.0 and ointment, or cream, or gel, or emulsion, or liniment base 80.0-99.9. The use of composition enhances wound- and burn-healing activity, promotes an additional development of antiallergic specific effect expressing as an attenuation of contact dermatitis course severity. EFFECT: enhanced effectiveness of a composition. 3 tbl, 6 ex

Description

 The invention relates to medicine, in particular to compositions for the treatment of wounds, burns and dermatitis, containing products of microbiological synthesis.

 For the treatment of wounds and burns, compositions containing polyunsaturated fatty acids / 1 / are widely used. Basically, these compounds are obtained from vegetable edible oils (linetol, rosehip and sea buckthorn oil, carotoline) or from animal raw materials (arachiden) or from seafood (eikonol, cod fish oil, polyene). The compositions used do not contain or include in a small amount essential for the human body γ-limonoic acid. Known lipid product of microbiological synthesis of mycelial fungus Mucor lusitanicus BKMF-306 D, containing linolenic acid, exhibiting a high specific pharmacological activity in the treatment of wounds / 2 /.

 The lipid product of microbiological synthesis is produced under the experimental conditions of the Institute of Microbiology of the Russian Academy of Sciences. Its disadvantages include: the difficulty of accurate dosing (oily liquid spilled into vials), the inconvenience of applying to wound surfaces (spreadability, slow absorption of the skin).

 The purpose of the invention is to increase the pharmacological activity in the treatment of wounds, burns, contact and allergic dermatitis; giving satisfactory consumer qualities (ease of dosing and application) of the lipid product of microbiological synthesis containing γ-linolenic acid.

This goal is achieved in that the proposed composition, including the product of microbiological synthesis of the mycelial fungus Mucor lusitanicus BKMF-306 D, further comprises an ointment (or cream, or gel, or emulsion, or liniment) base in the following ratio of components, wt.%:
The product of microbiological synthesis containing γ-linolenic acid - 0.1 - 20.0
Ointment, or cream, or gel, or emulsion, or liniment base - 80.0 - 99.9
To study the specific activity of the proposed composition (ointments, creams, gels, emulsions, liniments with a content of from 0.1 to 20.0% of the lipid product of the microbiological synthesis of the mycelial fungus Mucor Lusitanicus), experimental models of full-layer skin wounds and an alcohol-gauze burn in rats are used; contact allergic dermatitis in guinea pigs.

 The model of full-layer skin wounds was performed on outbred male rats (weight on average 200 g). The area of the wounds, into the edges of which were inserted Teflon rings protruding above the surface of the skin and closed on top with a cellophane film, reached 400 mm. The stimulating reparative processes were applied to the surface of wounds on the 2nd day after surgery for 5 days. On the 6th day after the operation, the Teflon rings were removed and the wound healed under the resulting jet.

 The anti-burn effect was studied in an experimental model of an alcohol-gauze burn of a 30 second exposure in rats. The agent stimulating reparative processes was applied daily in 2 doses for 7 days to the surface of the focus, starting from the 1st day of the experiment.

 Experimental dermatitis was reproduced on white guinea pigs (weight on average 550 - 600 g). 2,4-dinitrochlorobenzene in the form of an alcohol-acetone solution was used as a lung allergen. A sensitization center was created on the back (900 mm area) of guinea pigs, from which the coat was previously removed. A solution of dinitrochlorobenzene in an amount of 0.1 ml was rubbed into the skin of the back 1 time per day for 5 days.

 The severity of developed dermatitis was judged by the general condition and behavior of the animals. Systematically on 1, 3, 9, 11, 13 days after the start of serial application of the allergen, changes in the skin were observed. The severity of local skin manifestations was indicated in arbitrary units (points) according to Suvorov S.V. The therapeutic agent was applied evenly over the entire application area with a glass spatula 2 to 3 hours after the first of five serial applications of dinitrochlorobenzene. Manipulation was carried out daily 1 to 2 times a day until local manifestations disappeared.

 Wounds, burns, allergic contact dermatitis, reproduced according to the above experimental animal models, were treated with the formulations reflected in the claims, as illustrated by the following specific examples.

Example 1. Take 99.9 g of 3% glycerogel methylcellulose-65, obtained by known technology. The ratio of the ingredients of the glycerogel of methyl cellulose can vary, if necessary, the introduction of additional components that provide satisfactory consumer qualities of the gel (preservatives, odor correctants, stabilizers, anesthetics, antiseptics) is possible. 0.1 g of the lipid product of microbiological synthesis containing γ-linoleic acid is introduced into the gel base and carefully dispersed using a turbine or other type of mixer until a homogeneous mass of creamy consistency is obtained. The composition of the prepared gel composition has the following ratio of ingredients, wt.%:
The product of microbiological synthesis containing γ-linolenic acid - 0.1
Gel base (methyl cellulose glycerogel) - 99.9
Example 2. Take 99.0 g of 4% collagen gel obtained by known technology. The ratio of collagen gel ingredients can vary; if necessary, it is possible to introduce additional components into the collagen base that provide satisfactory consumer qualities of the gel. 1.0 g of microbiological synthesis product containing γ-linolenic acid is introduced into the collagen base, and it is carefully dispersed using a turbine or other type of mixer until a homogeneous mass of creamy consistency is obtained. The composition of the prepared gel composition has the following ratio of ingredients, wt.%:
The product of microbiological synthesis containing γ-linolenic acid - 1
Gel base (methyl cellulose glycerogel) - 99
Example 3. In accordance with generally accepted rules, an emulsion gel base is prepared by fusion and dispersion of 5.0 g of vegetable oil (sunflower, or soy, or cotton, or corn, or other), 5.0 g of emulsion waxes (or emulsifier N 1, or emulsifier T -2, or another emulsifier) and 90 ml of purified water. The ratio of the components of the cream base may vary. If necessary, additional ingredients can be introduced into the cream base to ensure satisfactory consumer qualities of the cream (fragrance, preservatives, stabilizers, antiseptics). 95.0 g of the obtained emulsion cream base are taken and 5.0 g of the microbiological synthesis product containing γ-linolenic acid is introduced into the emulsion cream base with thorough mixing on a turbine or other type of mixer until a homogeneous mass of creamy consistency is formed. The composition of the prepared cream composition has the following ratio of ingredients, wt.%:
The product of microbiological synthesis containing γ-linolenic acid - 5
Emulsion cream base (an alloy of vegetable oil, emulsifier and water) - 95
Example 4. Prepare an absorption ointment base by fusion under heating with stirring in accordance with generally accepted rules 61.4 g of polyethylene oxide 400 and 26.6 g of polyethylene oxide 1500 and 2.0 g of tween 80 (or another emulsifier). The ratio of the ingredients of the ointment base may vary. If necessary, it is possible to introduce additional components that provide satisfactory consumer qualities of the ointment (odor correctants, preservatives, stabilizers, antiseptics, anesthetics). 10.0 g of a microbiological synthesis product containing γ-linolenic acid is introduced into the obtained ointment base when dispersed using a turbine or other type of mixer until a homogeneous mass of creamy consistency is formed. The composition of the prepared cream composition has the following ratio of ingredients, wt.%:
The product of microbiological synthesis containing γ-linolenic acid - 10
Absorption ointment base (alloy of polyethylene oxides and emulsifier) - 90
Example 5. 15.0 g of a microbiological synthesis product containing γ-linolenic acid are weighed, 1.2 g of lecithin (or another emulsifier) is added, and mixed thoroughly with a glass rod. The resulting mixture of microbiological synthesis product and lecithin is injected with intensive dispersion using a turbine or other type of mixer in 83.8 ml of purified water until a homogeneous white or yellowish liquid resembling milk is obtained. The ratio of the ingredients of the emulsion base can vary, it is possible to introduce additional components that provide satisfactory consumer qualities of the emulsion (preservatives, stabilizers, flavoring agents of the hydrogen index). The composition of the prepared emulsion has the following ratio of components, wt.%:
The product of microbiological synthesis containing γ-linolenic acid - 15
Emulsion base (other emulsion preservatives: lecithin and water) - 85
Example 6. Weigh 20.0 g of the product of microbiological synthesis, 80.0 g of vegetable oil (sunflower, or soybean, or cotton, or corn, or other), mix thoroughly with a glass rod until an oily liquid (liniment) is formed. It is possible to introduce additional components into the liniment that provide satisfactory consumer qualities of the liniment (preservatives, antiseptics, stabilizers, flavoring agents). The composition of the prepared liniment has the following ratio of components, wt.%:
The product of microbiological synthesis containing γ-linolenic acid - 20
Liniment base (other liniment ingredients) - 80
The compositions described in examples 4 and 5 were applied to rat full-layer skin wounds reproduced according to the above experimental model. The compositions indicated in examples 4 and 6, smeared the burn wounds obtained using the model of alcohol-gauze burn 30-second exposure in rats. Given in examples 1, 2, 3, the compositions were treated contact allergic dermatitis caused in Guinea pigs by a known method.

 In each specific case (treatment of wounds, burns, dermatitis), all animals were divided into 3 groups: experimental (therapeutic agent - the proposed composition), comparative (application of the comparative preparation - prototype - microbiological synthesis product containing γ-linolenic acid); control (untreated animals). The healing of wounds, burns, the severity of skin manifestations with dermatitis was evaluated visually and planimetrically. Indices: accelerating the healing of wounds and burns and the index of reducing the severity of skin manifestations were calculated in relation to the control group of animals.

 The results of the influence of the proposed compositions (ointments, creams, gels, emulsions, liniments containing the lipid product of microbiological synthesis in a concentration of from 0.1 to 20.0%) on the course of experimental dermatitis, healing of wounds and burns in animals are presented in table. 13.

 In the table. Figures 1 and 2 show the data of a planimetric study, as well as the timing of the primary scab falling off and the healing of full-layer skin wounds and burns. The above results show that under the influence of formulations 4, 5, 6 with a content of 10, 15, 20% of the product of microbiological synthesis, respectively, the healing of skin and burn wounds is significantly accelerated, all phases of the wound process proceed much faster in time than in the control. The ointment, emulsion, and liniment containing the lipid product of microbiological synthesis are superior to the prototype (the product of microbiological synthesis) in its wound and burn healing activity. Indices of accelerating the healing of wounds and burns in experimental groups of animals treated with 10% ointment and 15% emulsion (compounds 4 and 5), 20% liniment (composition 6) were 34.3 - 37.7%, 38.1%, 30 , 5%, respectively, and in the comparison group (treatment with a product of microbiological synthesis in a dose equivalent to the amount of ointment, liniment or emulsion applied) - 28.8% and 19.3% (wounds and burns).

 Thus, the product of microbiological synthesis, ointment (composition 4), emulsion (composition 5), emulsion (composition 5), liniment (composition 6), is significantly higher than its own stimulating reparative processes activity by 30.9 - 32.3% (in the treatment of wounds) and by 58.0 - 77.7% (in the treatment of burns).

 Tab. 3 contains data on the effects of 0.1% and 1% gels and 5% cream of the lipid product of microbiological synthesis (formulations of examples 1 to 3) on the course of experimental dermatitis in guinea pigs. So, already on the 1st day after a single cutaneous application of a solution of dinitrochlorobenzene in all control animals, moderate hyperemia appeared (1 point). After each subsequent application of the allergen, the severity of local changes was aggravated, and by 9–11 days of the disease, sharp damage to the skin was observed with the formation of a deep hemorrhagic crust (5 points). There was also a rise in temperature, a sharp swelling of the tissues, lethargy, inhibition of the motor activity of animals.

 Treatment of experimental animals with 0.1% and 1% gels and 5% cream of the lipid product of microbiological synthesis (compositions of examples 1, 2, 3) led to a complete or partial restoration of the initial parameters of the skin by the 13th day of the experiment. In guinea pigs, moderate hyperemia and swelling were observed, which disappeared at the end of the experiment (13 days), while island-inflammatory phenomena predominated in the control group during this period. Indices for reducing the severity of skin manifestations ranged from 72.2 to 82.2% (in the case of applying 0.1% and 1% gel and 5% cream of the product of microbiological synthesis, respectively).

 Thus, the proposed composition for the treatment of wounds, burns and dermatological disorders, containing the lipid product of microbiological synthesis (from 0.1 to 20.0%) and ointment (or gel, or cream, or emulsion, or liniment) base (from 80, 0 to 99.9%) significantly exceeds (approximately 3.9 - 32.3% in the treatment of wounds and 58.0 - 77.7% in the treatment of burns) therapeutic activity of the prototype (the product of microbiological synthesis), additionally exhibits a specific anti-allergic activity, expressed in a decrease of 72.2 - 82.2% more STI treatment of contact dermatitis.

Literature:
1. The register of medicines of Russia (addition). -M .: Infarmhim; 1994, 479 p.

 2. RF patent N 2022019, C 12 P 7/64, 1994.

Claims (1)

1. The composition for the treatment of wounds, burns, contact and allergic dermatitis, including the product of microbiological synthesis of mycelial fungus Mucor lusitanicus BKMF-306 D containing γ-linolenic acid, characterized in that it additionally contains ointment, or cream, or gel, or emulsion , or liniment base in the following ratio of components, wt.%,
The product of microbiological synthesis containing γ-linolenic acid - 0.1 - 20.0
Ointment, or cream, or gel, or emulsion, or liniment base - 80.0 - 99.0

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