RU2796727C1 - Composition for elimination of herpetic eruptions symptoms - Google Patents

Abstract

FIELD: pharmaceutical; cosmetic industries.

SUBSTANCE: invention relates to a composition for eliminating the symptoms of herpetic eruptions. Composition for eliminating the symptoms of herpetic eruptions in the form of a gel containing a local anesthetic component selected from the following group: dikain, polidocanol, anesthesin, pyromecaine, lidocaine; astringent selected from the following group: synthetic tannin, oak bark extract, sage leaf extract, zinc oxide, zinc carbonate, silver nitrate, basic bismuth nitrate; an antiviral component selected from the following group: acyclovir, dipotassium glycyrrhizinate, ammonium glycyrrhizinate, licorice extract; regenerating component selected from the following group: D-panthenol, glycine, alanine, asparagine; wound healing component selected from the following group: allantoin, aloe extract, oat extract, bisabolol, vitamin A, vitamin E, vitamin PP, moisturizing component — glycerin, and base, with the following content of components, wt.%: local anesthetic component — 0.25–6.0, astringent component 0.5–5.0, antiviral component — 0.1–4.0, regenerating component — 0.2–2.5, wound healing component — 0.1–1.5, glycerin — 0.4–2.5, base — up to 100.

EFFECT: above composition is effective for eliminating the symptoms of herpetic eruptions, characterized by a synergistic interaction of the components.

7 cl, 12 ex

Description

The invention relates to a composition intended for complex care of the mucous membranes of the mouth and lips, and can be used in the pharmaceutical or cosmetic industry.

The claimed composition is used for acute lesions of the mucous membranes of the mouth and lips caused by the herpes simplex virus (labial herpes) and accompanied by dryness, ulceration, redness, cracks and itching.

The prior art is known stable composition for the treatment of lesions associated with herpes virus infections, in the form of a cream or gel containing trichloroacetic acid in an amount of less than 6 wt. % (RF patent No. 2545918). The known composition is used in the treatment of herpes I (herpes simplex) and herpes II (genital herpes). However, when applied, a burning sensation occurs. In addition, trichloroacetic acid is toxic and can cause swelling and redness of the skin. When using a known composition, age spots, rashes and burns may appear.

Known therapeutic composition for application and increased penetration into damage to epithelial tissue caused by at least one of the viruses, bacteria, fungi or toxin containing an organic halide, in particular benzalkonium chloride, a liquid carrier containing isopropyl alcohol and water, and benzocaine (RF patent No. 2586969). The known composition has good penetrating power and is used for a wide range of tissue damage caused by the herpes virus, as well as in the treatment of other tissue damage caused by related viruses, as well as painful tissue damage caused by bacteria and fungi.

However, benzalkonium chloride acts mainly on Herpes simplex type 2, which usually causes genital herpes, and does not work on Herpes simplex type 1, which causes perioral herpes.

Known means for preventing or treating a viral infection caused by the herpes simplex virus. As an active component, the agent contains a therapeutically effective amount of an extract of the stem (stem with bark), bark, branch or stem without bark of the Ficus arnottiana plant and a pharmaceutically acceptable carrier that allows it to be made in the form, for example, of a cream or gel (RF patent No. 2584245). The known agent contains from about 5% to about 99%, preferably from 5 to 50% by weight of the extract of the Ficus arnottiana plant. The Ficus arnottiana plant extract is contained in the composition in an amount effective to achieve the desired therapeutic response in a particular patient without being toxic to the patient or causing severe side effects in the patient. However, the use of a product containing plant extracts can cause an allergic reaction. The activity of the extract directly depends on the weather and natural conditions of the growth of the source of raw materials, which ultimately makes the well-known agent unstable. In addition, the extract of the plant Ficus arnottiana has a weak antiviral effect.

Known means for external use, which includes a peptide from the group of alloferons, allostatin-1 and excipients (RF patent No. 2338553). The known agent is made in the form of a gel and is used to treat diseases of the skin and mucous membranes caused by the herpes virus, human papillomavirus, as well as cosmetic skin defects. However, allostatin-1, which is part of the known remedy, can cause the appearance of additional herpetic eruptions, which can be perceived as a deterioration in the condition. Also, the use of allostatin-1 in children and pregnant women is limited and requires prior consultation with a specialist.

Known composition for the treatment of herpetic infections, including as active components of triazavirin in the amount of 1.5-2.0 wt. % and sea buckthorn oil in the amount of 1.5-2.0 wt. %, and organosilicon glycerohydrogel composition Si(C ₃ H ₇ O ₃ ) ₄ ⋅ 6C ₃ H ₈ O ₃ ⋅ 24H ₂ O (RF patent No. 2560686) as the goal base. The known composition has a high therapeutic activity and an increased rate of epithelialization of pathological elements in the complete absence of negative side effects. However, the mechanism of action of triazavirin is the inhibition of viral RNA synthesis and replication of genomic fragments, that is, the composition acts only on RNA viruses, while the herpes simplex virus is a DNA virus. In addition, triazavirin has limitations for use during pregnancy and lactation.

Thus, at present, there is a need to develop a gel composition for complex care of the mucous membranes of the mouth and lips to eliminate the symptoms of herpetic eruptions, as well as to expand the arsenal of domestically produced antiviral drugs.

The objective of the invention is to create an effective composition for the complex care of the mucous membranes of the mouth and lips, which has the ability to quickly relieve the symptoms of labial herpes and prevent the risk of developing a secondary bacterial infection that does not have side effects.

In the course of the studies, the task was solved by creating a composition for eliminating the symptoms of herpetic eruptions, containing a local anesthetic component selected from the group: dikain, polidocanol, anesthesin, pyromecaine, lidocaine; astringent selected from the group: synthetic tannin, oak bark extract, sage leaf extract, St. John's wort extract, zinc oxide, zinc carbonate, zinc sulfate, silver nitrate, basic bismuth nitrate; an antiviral component selected from the group: acyclovir, dipotassium glycyrrhizinate, ammonium glycyrrhizinate, licorice extract, potato shoot extract; regenerating component selected from the group: D-panthenol, dioxomethyltetrahydropyrimidine, proteinogenic amino acids: glycine, alanine, valine, isoleucine, leucine, proline, series, threonine, cysteine, methionine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, arginine, histidine, phenylalanine, tyrosine, tryptophan; a wound healing component selected from the group: allantoin, aloe extract, oat extract, bisabolol, vitamin A, vitamin E, vitamin PP, a moisturizing component - glycerin, and a base, with the following content of components, wt. %:

Local anesthetic component 0.25-6.0 Astringent component 0.5-5.0 Antiviral component 0.1-4.0 Regenerating component 0.2-2.5 Wound healing component 0.1-1.5 Glycerol 0.4-2.5 The basis up to 100

Preferably, the regenerating component may be tripeptides, oligopeptides, pentapeptides, vegetable keratin, animal collagen, animal collagen, madecassoside, vegetable oil.

Preferably, the vegetable oil is shea butter, wheat oil, olive oil, sunflower oil, coconut oil.

Preferably, the base contains water, emollient, thickener, preservative, pH regulator.

Preferably, the emollient is selected from C12-15 alkyl benzoate, ethylhexyl palmitate, ethylhexyl stearate.

Preferably the thickener is selected from carbomer, dehydroxanthan gum; acrylate copolymer.

Preferably, the preservative is selected from the complexes: potassium sorbate, sodium benzoate, benzyl alcohol, water; methyl paraben, ethyl paraben, propyl paraben, butyl paraben, phenoxyethanol; chlorphenesin, 1,2-hexanediol, phenylpropanol.

Preferably, the pH regulator is selected from lactic acid, citric acid, arginine.

Preferably, the composition according to any of the paragraphs contains from 1.0 to 7.0 wt. % emollient, from 0.2 to 2.0 wt. % thickener, from 0.5 to 1.1 wt. % preservative, from 0.1 to 1.0 wt. % pH regulator and up to 100 wt. % water.

Preferably, the composition is in the form of a gel.

The technical result achieved by the proposed composition is due to its new properties discovered during research.

It was found that due to the synergistic interaction of the components, the proposed composition has a complex effect on the mucous membrane: relieves itching, pain, "tingling", eliminates redness and irritation, has an astringent, drying, antiviral and anti-inflammatory effect.

The astringent component has antipruritic and anti-inflammatory effects, inhibiting the activity of inflammatory enzymes, the release of histamine and creating a thin protective film on the skin. The local anesthetic component also has antipruritic and analgesic effects, as it has an anesthetic effect on the receptors of the skin and mucous membranes. On the other hand, it enhances the effect of the astringent component, binding skin proteins and tissue fluid proteins into a thin film on the skin surface and promotes the healing of erosions.

The antiviral component, having additional anti-inflammatory activity, enhances the anti-inflammatory effect of the astringent component, thus reducing the duration of the course of herpes.

The regenerating component prevents the appearance of microcracks. The wound healing component has a pronounced effect on the regeneration of skin cells, stimulates the healing of the skin and wounds. The wound healing component also has an astringent effect, complementing the effect of the astringent component.

The ratio of the components in the proposed composition is selected experimentally, taking into account the therapeutic activity and is optimal, which makes it possible to obtain a technical result corresponding to the task.

An acceptable base that allows the proposed composition to be made in the form of a gel makes it possible to use the proposed composition for acute lesions of the mucous membranes of the mouth and lips, since it has a pH close to that of the skin and, therefore, does not irritate the skin, easily releases active substances, ensuring their high bioavailability .

The method of obtaining the proposed composition.

Part of the calculated amount of water is poured into the reactor.

Glycerin, an astringent component, an antiviral component, a wound healing component, taken in calculated amounts, are added with stirring. The mixture is stirred with low heat until complete dissolution.

The calculated amount of thickener is added to the resulting mixture and stirred for 15-30 minutes. Using a homogenizer, emulsify the mass until a homogeneous emulsion is obtained. Calculated amounts of a preservative, an emollient, a regenerating component, a local anesthetic component are introduced into the resulting emulsion and mixed again. The resulting mixture is cooled to room temperature, the rest of the water, the required amount of pH regulator are added and stirred until a homogeneous thick mass is formed.

The resulting composition is checked for quality and packaged in consumer packaging.

The proposed composition is characterized by the necessary physico-chemical and specialized properties, as well as stability during the established shelf life.

Below are examples of the manufacture of the proposed composition. The examples are given to illustrate the invention without limiting its scope.

Example 1

Synthetic tannin, acyclovir and allantoin are added to the prepared mixture of glycerin and water. The mixture is stirred with low heat until complete dissolution. Carbomer is added to the mixture, stirred for 15 minutes and emulsified. A preservative (methyl-paraben complex, ethylparaben, propylparaben, butylparaben, phenoxyethanol), ethylhexyl palmitate, D-panthenol, lidocaine is added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and lactic acid are added and stirred until smooth.

The result is a gel with a synthetic tannin content of 0.5 wt. %, acyclovir 3.5 wt. %, D-panthenol 2.5 wt. %, allontoin 0.1 wt. %, lidocaine 5.8 wt. %, glycerol 3.0 wt. %

Example 2

Synthetic tannin, acyclovir and allantoin are added to the prepared mixture of glycerin and water. The mixture is stirred with low heat until complete dissolution. Dehydroxanthan gum is added to the mixture, stirred for 15 minutes and emulsified. A preservative (methyl paraben complex, ethyl paraben, propyl paraben, butyl paraben, phenoxyethanol), ethylhexyl palmitate, D-panthenol, lidocaine is added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and lactic acid are added and stirred until smooth.

The result is a gel with a synthetic tannin content of 0.5 wt. %, acyclovir 0.1 wt. %, D-panthenol 0.2 wt. %, allantoin 0.1 wt. %, lidocaine 0.25 wt. %, glycerol 0.4 wt. %.

Example 3

Synthetic tannin, licorice extract and allantoin are added to the prepared mixture of glycerin and water. The mixture is stirred with low heat until complete dissolution. Carbomer is added to the mixture, stirred for 15 minutes and emulsified. A preservative (methyl-paraben complex, ethylparaben, propylparaben, butylparaben, phenoxyethanol), ethylhexyl stearate, D-panthenol, pyromecaine is added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and lactic acid are added and stirred until smooth.

The result is a gel with a synthetic tannin content of 2.5 wt. %, licorice extract 1.5 wt. %, D-panthenol 0.5 wt. %, allantoin 0.1 wt. %, pyromecaine 6.0 wt. %, glycerol 1.8 wt. %.

Example 4

Zinc oxide, licorice extract and vitamin A are added to the prepared mixture of glycerin and water. The mixture is stirred at low heat until completely dissolved. Carbomer is added to the mixture, stirred for 25 minutes and emulsified. A preservative (methyl-paraben complex, ethylparaben, propylparaben, butylparaben, phenoxyethanol), ethylhexyl stearate, glycine, pyromecaine is added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and citric acid are added and stirred until smooth.

The result is a gel with a zinc oxide content of 3.4 wt. %, licorice extract 3.5 wt. %, vitamin A 0.5 wt. %, glycine 2.1 wt. %, pyromecaine 6.0 wt. %, glycerol 2.5 wt. %.

Example 5

Zinc carbonate, dipotassium glycyrrhizinate and bisabolol are added to the prepared mixture of glycerin and water. The mixture is stirred with low heat until complete dissolution. The acrylate copolymer is added to the mixture, stirred for 30 minutes and emulsified. A preservative (methyl-paraben complex, ethylparaben, propylparaben, butylparaben, phenoxyethanol), ethylhexyl stearate, glycine, lidocaine is added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and citric acid are added and stirred until smooth.

The result is a gel with a zinc carbonate content of 5.0 wt. %, dipotassium glycyrrhizinate 3.0 wt. %, bisabolol 1.5 wt. %, glycine 1.1 wt. %, lidocaine 4.0 wt. %, glycerol 1.8 wt. %.

Example 6

Synthetic tannin, dipotassium glycyrrhizinate and allantoin are added to the prepared mixture of glycerin and water. The mixture is stirred with low heat until complete dissolution. Carbopol is added to the mixture, stirred for 20 minutes and emulsified. A preservative (potassium sorbate complex, sodium benzoate, benzyl alcohol, water), C12-15 alkyl benzoate, D-panthenol, polidocanol are added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and citric acid are added and stirred until smooth.

The result is a gel with a synthetic tannin content of 3.5 wt. %, dipotassium glycyrrhizinate 2.0 wt. %, allantoin 0.75 wt. %, D-panthenol 1.5 wt. %, polidocanol 4.0 wt. %, glycerin 0.85 wt. %.

Example 7

Oak bark extract, dipotassium glycyrrhizinate and vitamin E are added to the prepared mixture of glycerin and water. The mixture is stirred at low heat until completely dissolved. Carbopol is added to the mixture, stirred for 20 minutes and emulsified. A preservative (potassium sorbate complex, sodium benzoate, benzyl alcohol, water), C12-15 alkyl benzoate, alanine, dicain are introduced into the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and lactic acid are added and stirred until smooth.

The result is a gel with an oak bark extract content of 3.5 wt. %, dipotassium glycyrrhizinate 2.0 wt. %, vitamin E 1.5 wt. %, alanine 0.6 wt. %, dicaine 5.0 wt. %, glycerol 1.4 wt. %.

Example 8

Silver nitrate, ammonium glycyrrhizinate and vitamin E are added to the prepared mixture of glycerin and water. The mixture is stirred at low heat until completely dissolved. Dehydroxanthan gum is added to the mixture, stirred for 30 minutes and emulsified. A preservative (potassium sorbate complex, sodium benzoate, benzyl alcohol, water), C12-15 alkyl benzoate, asparagine, anestezin are introduced into the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and arginine are added and stirred until smooth.

The result is a gel with a silver nitrate content of 5.0 wt. %, ammonium glycyrrhizinate 2.8 wt. %, vitamin E 1.2 wt. %, asparagine 0.9 wt. %, anesthesin 4.8 wt. %, glycerol 2.5 wt. %.

Example 9

Bismuth nitrate basic, ammonium glycyrrhizinate and aloe extract are added to the prepared mixture of glycerin and water. The mixture is stirred with low heat until complete dissolution. Carbomer is added to the mixture, stirred for 15 minutes and emulsified. A preservative (chlorphenesin complex, 1,2-hexanediol, phenylpropanol), ethylhexyl stearate, vegetable keratin, anesthesin is added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and arginine are added and stirred until smooth.

The result is a gel with a basic bismuth nitrate content of 2.0 wt. %, ammonium glycyrrhizinate 3.8 wt. %, aloe extract 0.7 wt. %, vegetable keratin 1.5 wt. %, anesthesin 4.8 wt. %, glycerin 0.5 wt. %.

Example 10

Sage leaf extract, acyclovir and vitamin PP are added to the prepared mixture of glycerin and water. The mixture is stirred with low heat until complete dissolution. Dehydroxanthan gum is added to the mixture, stirred for 25 minutes and emulsified. A preservative (chlorphenesin complex, 1,2-hexanediol, phenylpropanol), ethylhexyl stearate, shea butter, polidocanol is added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and arginine are added and stirred until smooth.

The result is a gel containing sage leaf extract 4.7 wt. %, acyclovir 2.5 wt. %, vitamin PP 1.4 wt. %, shea butter 2.1 wt. %, polidocanol 0.25 wt. %, glycerol 2.2 wt. %.

Example 11

Sage leaf extract, dipotassium glycyrrhizinate and allantoin are added to the prepared mixture of glycerin and water. The mixture is stirred with low heat until complete dissolution. Carbopol is added to the mixture, stirred for 15 minutes and emulsified. A preservative (chlorphenesin complex, 1,2-hexanediol, phenylpropanol), ethylhexyl palmitate, wheat oil, polidocanol is added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and arginine are added and stirred until smooth.

The result is a gel with a sage leaf extract content of 0.7 wt. %, dipotassium glycyrrhizinate 0.5 wt. %, allantoin 1.4 wt. %, wheat oil 2.1 wt. %, polidocanol 0.25 wt. %, glycerol 0.9 wt. %.

Example 12

Zinc carbonate, licorice extract and oat extract are added to the prepared mixture of glycerin and water. The mixture is stirred with low heat until complete dissolution. Carbopol is added to the mixture, stirred for 15 minutes and emulsified. A preservative (methyl-paraben complex, ethylparaben, propylparaben, butylparaben, phenoxyethanol), ethylhexyl palmitate, coconut oil, polidocanol is added to the resulting emulsion and mixed again. The mixture is cooled to room temperature, water and lactic acid are added and stirred until smooth.

The result is a gel with a zinc carbonate content of 3.7 wt. %, licorice extract 0.5 wt. %, oat extract 1.4 wt. %, coconut oil 1.1 wt. %, polidocanol 3.2 wt. %, glycerol 2.2 wt. %.

In all examples, the achievement of the claimed technical result was confirmed.

In relation to the proposed composition, extended experimental laboratory and clinical laboratory studies were carried out.

According to the expert opinion, the composition of the proposed composition consists of generally accepted, approved ingredients and does not cause objections.

The purpose of the experimental laboratory study was to assess the anti-inflammatory (anti-edematous) effect on the experimental model of edema, and in order to assess the clinical effectiveness, the pigmentometry index (according to the vascular type) was determined, reflecting the degree of skin erythema, as one of the constituent signs of inflammation.

Experimental studies to study the anti-inflammatory effect of the proposed composition were carried out on 20 white rats, males, Wistar line, weighing 210-230 g, which are in the standard vivarium mode, in accordance with the rules approved by GOST R 53434-2009 "Principles of Good Laboratory Practice" . Intact animals served as controls, which, like the experimental ones, were on a standard vivarium regime, but they did not receive skin applications of the studied compounds.

The determination of the anti-inflammatory (anti-edematous) action was carried out according to the method of F.P. Trinus et al.

When evaluating the results obtained, we noted that the proposed composition quite actively inhibited the process of edema development, and the effect was directly proportional to the exposure time. So, 1 hour after its application, the anti-inflammatory effect was 11.0%, after 2 hours the effect increased to 25.5%, after 3 hours the anti-edematous effect increased to 36.0%. A day after its application, the anti-edematous effect was maximum and amounted to 65.0%.

Clinical studies to assess the level of erythema were conducted on 10 women, aged 28 to 67 years.

Measurements of indicators of the degree of erythema were carried out at the same time of the day - between 10 and 15 o'clock in the afternoon, at the same ambient temperature of 22-24 ° C, after the patient had previously adapted to the microclimate of the room for at least 10-15 minutes.

To evaluate the effectiveness of the proposed composition in relation to the level of erythema, all volunteers were previously artificially induced erythema in the forearm using a source of UV radiation (simulator). An objective evaluation of the effectiveness of this indicator was carried out after a single application of the studied lip gel to the skin, its complete drying and absorption, after 15-20 minutes.

The results of the study on assessing the level of pigmentometry by vascular type showed that under the influence of the studied lip gel, the level of erythema statistically significantly decreased after its use by 9.3% compared with the initial level (Fig. 1), which indicates the effectiveness of this agent in relation to reducing the level of erythema (redness) of the skin, which is typical for signs of inflammation and irritation.

Examination conclusions:

- the proposed composition has an anti-inflammatory (decongestant) effect, with the most pronounced effect in a day, equal to 65.0%, respectively;

- the proposed composition has a statistically significant anti-erythema effect equal to 9.3%;

- the proposed composition can be recommended for a wide practical application, in accordance with the declared properties according to the studied parameters.

The claimed composition for eliminating the symptoms of herpetic eruptions is an effective composition for complex care of the mucous membranes of the mouth and lips and does not have side effects.

Claims (13)

1. Composition to eliminate the symptoms of herpetic eruptions in the form of a gel containing a local anesthetic component selected from the group: dikain, polidocanol, anesthesin, pyromecaine, lidocaine; astringent selected from the group: synthetic tannin, oak bark extract, sage leaf extract, zinc oxide, zinc carbonate, silver nitrate, basic bismuth nitrate; an antiviral component selected from the group: acyclovir, dipotassium glycyrrhizinate, ammonium glycyrrhizinate, licorice extract; regenerating component selected from the group: D-panthenol, glycine, alanine, asparagine; wound healing component selected from the group: allantoin, aloe extract, oat extract, bisabolol, vitamin A, vitamin E, vitamin PP, moisturizing component - glycerin, and base, with the following content of components, wt.%: Local anesthetic component 0.25-6.0 Astringent component 0.5-5.0 Antiviral component 0.1 -4.0 Regenerating component 0.2-2.5 Wound healing component 0.1-1.5 Glycerol 0.4-2.5 The basis up to 100 2. Composition according to claim 1, in which the base contains water, emollient, thickener, preservative, pH regulator. 3. A composition according to claim 2 wherein the emollient is selected from C12-15 alkyl benzoate, ethylhexyl palmitate, ethylhexyl stearate. 4. Composition according to claim 2, in which the thickener is selected from carbomer, dehydroxanthan gum, acrylate copolymer. 5. Composition according to claim 2, in which the preservative is selected from the complexes: potassium sorbate, sodium benzoate, benzyl alcohol, water; methyl paraben, ethyl paraben, propyl paraben, butyl paraben, phenoxyethanol; chlorphenesin, 1,2-hexanediol, phenylpropanol. 6. The composition of claim 2, wherein the pH regulator is selected from lactic acid, citric acid, arginine. 7. The composition according to any one of paragraphs. 2-6 contains from 1.0 to 7.0 wt.% emollient, from 0.2 to 2.0 wt.% thickener, from 0.5 to 1.1 wt.% preservative, from 0.1 to 1, 0 wt% pH regulator and up to 100 wt% water.