RU2785542C2 - Composition for complex skin care in the treatment of dermatosis - Google Patents

Abstract

FIELD: complex skin care.

SUBSTANCE: invention relates to complex skin care in the treatment of various types of dermatoses and can be used in the pharmaceutical or cosmetic industry. The composition for complex skin care in the treatment of dermatoses contains synthetic tannin, a base, a local anesthetic component selected from the group: dikain, polidocanol, anesthesin, pyromecaine, lidocaine, with the following content of components, wt.%: synthetic tannin - 0.1-10.0, local anesthetic component - 0.1-10.0, base - up to 100.

EFFECT: invention provides antimicrobial activity and anti-inflammatory effect.

8 cl, 4 dwg, 1 tbl, 20 ex

Description

The invention relates to a composition intended for complex skin care in the treatment of various types of dermatoses, and can be used in the pharmaceutical or cosmetic industry.

In recent years, there has been an increase in the diversity and number of dermatological diseases. The most common causes of dermatoses are allergies, disruption of the immune system, infections, stress, metabolic disorders, non-compliance with personal hygiene rules, and an unfavorable environmental situation. A large group of dermatoses is accompanied by skin itching, which worsens the physical and psychological state of a person and negatively affects his performance and emotional state.

Among the main methods of treating dermatoses, the use of topical agents is one of the most effective and common.

There are various agents for external use that have a beneficial effect on the skin in dermatoses, containing various plant extracts (RU 2602474, A61K 8/04, A61K 8/92, A61K 8/97, 2015, EN 2014830, 1994, RU 2038073, A61K 7/48, 1995, RU 2242216, A61K 7/48, 2004, RU 2366406, A61K 8/02, A61K 36/28, A61K 8/67, 2009, RU 2452463, A61K 8/04, A61K 8/34, A61K 8/67, 2011), containing peptides (RU 2124353, A61K 7/48, A61K 45/06, 1995, RU 2572694, A61K 38/22 , А61Р 17/00.2010) containing hyaluronic acid (RU 2660350, A61K 8/67, A61K 8/73, A61K 8/97, 2017).

Known compositions exhibit varying degrees of effectiveness when used to treat dermatoses or alleviate its symptoms.

Closest to the claimed composition in technical essence and the achieved result is the composition of Delaskin cream (https://www.piluli.kharkov.ua/drugs/drug/delaskin-krem/), used for the treatment of inflammatory and itchy dermatoses, selected as prototype. Known composition, which is a cream, consisting of an active ingredient and an acceptable base. As an active ingredient, the cream contains a tannin - synthetic tannin Tamol PP. The known composition is effective in adults and children with irritation, inflammation and maceration of the skin, has a local anesthetic effect.

However, the known composition has a weak antipruritic activity, and can not be used in case of severe inflammation of the skin.

The objective of the invention is to create a composition for complex skin care in the treatment of dermatosis, which has a high antipruritic and anti-edematous activity, and is also effective for use in severe inflammation of the skin, without side effects.

In the course of the studies, the task was solved by creating a composition for complex skin care in the treatment of dermatosis, containing synthetic tannin and a base, and additionally containing a local anesthetic component selected from the group: dikain, polidocanol, anesthesin, pyromecaine, lidocaine, with the following content of components , wt. %:

Synthetic tannin - 0.1-10.0

Local anesthetic component selected from the group:

dicaine, polidocanol, anesthesin, pyromecaine, lidocaine - 0.1-10.0

Base - up to 100.

Preferably, the base composition contains a suitable base to be formulated as a cream.

Preferably, a suitable base for making the composition in the form of a cream contains water, an emulsifier, an emollient, a stabilizer, a film former, a preservative, a thickener.

Preferably, the composition as a base contains a suitable base, allowing it to be carried out in the form of a suspension.

Preferably, a suitable base to make the composition in the form of a suspension contains water, a film former, a thickener, an emulsifier, an emollient, a preservative, a gel former.

Preferably, the composition as a base contains a suitable base, allowing it to be carried out in the form of a solution.

Preferably, a suitable base for making the composition in the form of a solution contains water and a preservative.

Preferably, some of the solution can be placed in a spray bottle.

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 skin: the introduction of an additional local anesthetic component into the claimed composition, along with synthetic tannin, makes it possible to increase the therapeutic activity of the proposed composition by expanding the spectrum of antipruritic action, relieve pain symptoms of dermatoses, such as burning and itching. Synthetic tannin has antipruritic and anti-inflammatory effects, inhibiting the activity of inflammatory enzymes and the release of histamine, creating a thin protective film on the skin. The local anesthetic component has an antipruritic and analgesic effect on the receptors of the skin and mucous membranes, and on the other hand enhances the astringent effect of tannin, binding skin proteins and tissue fluid proteins into a thin film on the skin surface. This promotes healing of erosions on the skin, which helps protect damaged skin from microbial attack.

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. The best effect is achieved when using the proposed composition with a content of synthetic tannin from 1 to 10 wt. % and local anesthetic component from 1 to 10 wt. %.

Acceptable bases that make it possible to perform the proposed composition in the form of a cream, suspension and solution, provide the possibility of effective use of the proposed composition for weeping and dry dermatoses.

The use of a large list of substances in the proposed composition as a local anesthetic component and base allows you to expand the range of effective compositions for skin care for children and adults.

The method of obtaining the proposed composition.

The required amount of base components is melted at a temperature of 70-72°C, mixed and filtered. Estimated amounts of tannin and local anesthetic component are loaded into the prepared base, mixed and cooled to room temperature. The resulting composition is checked for quality and packaged in consumer packaging.

In the described method for obtaining the proposed composition, synthetic tannin is used that meets the requirements of the Pharmacopoeia; as a local anesthetic agent, dicaine, or polidocanol, or anesthesin, or pyromecaine, or lidocaine, is used, which meets the requirements of the pharmacopoeia; components suitable for skin use are used as base components.

Water (up to 100 wt. % in the base) is used as the components of the base, which makes it possible to obtain the proposed composition in the form of a cream, and can be used, for example:

as an emulsifier - Cetearyl alcohol (1.5-9.5 wt.%); Glyceryl stearate, PEG-100 stearate (1.5-9.5 wt.%); PEG-30 Dipolyhydroxy stearate (1.5-9.5 wt.%);

as an emollient - C12-15 Alkyl benzoate (1.5-7.0 wt.%); Ethylhexyl palmitate (1.5-7.0 wt.%); Ethylhexyl stearate (1.5-7.0 wt.%);

as a stabilizer - complex: Sodium acrylate / sodium acryloyldimethyl taurate copolymer (and) dimethicone and tridecet-6 (and) PEG / PPG-18/18 dimethicone (0.2-5.0 wt.%); Acrylates/palmet-25 acrylate copolymer (0.2-5.0 wt. %); Cellulose (0.2%-5.0 wt.%);

as a foaming agent - Amodimethicone (0.3-7.0 wt. %); Tridecet-12, cetrimonium chloride (0.3-7.0 wt.%); Cyclopentasiloxane, dimethiconol (0.3-7.0 wt. %);

as a preservative - complexes: Chlorphenesin, 1,2-Hexanediol, phenylpropanol (0.5-1.1 wt.%); Potassium sorbate, sodium benzoate, benzyl alcohol, water (0.5-1.1 wt.%); Methylparaben, ethylparaben, propylparaben, butylparaben, phenoxyethanol (0.5-1.1 wt.%);

as a thickener - Carbomer (0.05-4.0 wt.%); Dehydroxanthan gum (0.05-4.0 wt. %); Copolymer of acrylates (0.05-4.0 wt.%).

Water (up to 100 wt. % in the base) is used as the components of the base, which makes it possible to obtain the proposed composition in the form of a suspension, and can be used, for example:

as a film former - Cyclopentasiloxane (and) Polysilicone-11 (0.3-7.0 wt.%); Tridecet-12, cetrimonium chloride (0.3-7.0 wt.%); Cyclopentasiloxane, dimethiconol (0.3-7.0 wt. %);

as a thickener - Carbomer (0.05-5.0 wt.%); Polyquaternium-37 (0.05-5.0 wt.%); Acrylate copolymer (0.05-5.0 wt. %);

as an emulsifier - complexes: Cetearyl alcohol, ceteareth-25, polysorbate 60, PEG-100 stearate (1.0-7.0 wt.%); Cetearyl glucoside, sorbitan stearate, glyceryl stearate, cetearyl alcohol (1.0-7.0 wt. %); Cetearyl alcohol, lauryl myristyl alcohol, ceteareth-25, cetet-2 (1.0-7.0 wt.%).

as an emollient - Isopropyl palmitate (1.0-6.0 wt.%); Caprylic/capric triglycerides (1.0-6.0% by weight); Myristil myristate (1.0-6.0 wt.%);

as a preservative - Methylisothiazolinone (0.5-1.1 wt.%); Methylparaben, ethylparaben, propylene glycol (0.5-1.1 wt.%); Caprylyl glycol, phenylethyl alcohol (0.5-1.1 wt.%);

as a gelling agent - Dehydroxanthan gum (0.25-5.5 wt.%); Xanthan gum(s) guar gum (0.25-5.5% by weight); Xanthan gum (0.25-5.5%).

Water (up to 100 wt. %) and a preservative are used as components of the base, which makes it possible to obtain the proposed composition in the form of a solution, which, for example, can be complexes: Benzoic acid, sorbic acid, dehydroacetic acid, benzyl alcohol (0, 25-1.1 wt %); Benzoic acid, sorbic acid, dehydroacetic acid, caprylyl glycol, benzyl alcohol (0.25-1.1 wt.%); Hexanediol, benzyl alcohol (0.25-1.1 wt.%).

Below are examples of the manufacture of the proposed composition in the form of a cream, suspension and spray. The examples are given to illustrate the invention without limiting its scope. Cream composition.

Example 1

The required amount of base to obtain the cream is melted at a temperature of 72°C, mixed and filtered. The calculated amount of synthetic tannin and lidocaine is loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 1.11 wt. % and lidocaine 5.8 wt. %.

Example 2

The required amount of base to obtain the cream is melted at a temperature of 72°C, mixed and filtered. The calculated amount of synthetic tannin and lidocaine is loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 0.11 wt. % and lidocaine 9.5 wt. %.

Example 3

The required amount of base to obtain the cream is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and dikain is loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 10.0 wt. % and dicaine 10.0 wt. %.

Example 4

The required amount of base to obtain the cream is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and dikain is loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 5.0 wt. % and dicaine 8.0 wt. %.

Example 5

The required amount of base to obtain the cream is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and polidocanol are loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 10.0 wt. % and polidocanol 10.0 wt. %.

Example 6

The required amount of base to obtain the cream is melted at a temperature of 71°C, mixed and filtered. The calculated amount of synthetic tannin and polidocanol are loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 0.1 wt. % and polidocanol 8.4 wt. %.

Example 7

The required amount of base to obtain the cream is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and anesthesin is loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 0.3 wt. % and anesthesin 9.8 wt. %.

Example 8

The required amount of base to obtain the cream is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and anesthesin is loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 2.5 wt. % and anesthesin 10.0 wt. %.

Example 9

The required amount of base to obtain the cream is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and pyromecaine is loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 10 wt. % and anesthesin 0.1 wt. %.

Example 10

The required amount of base to obtain the cream is melted at a temperature of 72°C, mixed and filtered. The calculated amount of synthetic tannin and pyromecaine is loaded into the prepared base, mixed and cooled to room temperature. The result is a cream with a synthetic tannin content of 7.4 wt. % and anesthesin 0.32 wt. %.

Composition in the form of a suspension.

Example 11.

The required amount of base to obtain a suspension is melted at a temperature of 72°C, mixed and filtered. The calculated amount of synthetic tannin and anesthesin is loaded into the prepared base, mixed and cooled to room temperature. The result is a suspension with a synthetic tannin content of 6.2 wt. % and anesthesin 0.38 wt. %.

Example 12.

The required amount of base to obtain a suspension is melted at a temperature of 72°C, mixed and filtered. The calculated amount of synthetic tannin and lidocaine are loaded into the prepared base, mixed and cooled to room temperature. The result is a suspension with a synthetic tannin content of 8.2 wt. % and lidocaine 9.4 wt. %.

Example 13

The required amount of base to obtain a suspension is melted at a temperature of 72°C, mixed and filtered. The calculated amount of synthetic tannin and pyromecaine is loaded into the prepared base, mixed and cooled to room temperature. The result is a suspension with a synthetic tannin content of 4.7 wt. % and pyromecaine 2.1 wt. %.

Example 14

The required amount of base to obtain a suspension is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and dikain is loaded into the prepared base, mixed and cooled to room temperature. The result is a suspension with a synthetic tannin content of 2.5 wt. % and dicaine 10.0 wt. %.

Example 15

The required amount of base to obtain a suspension is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and polidocanol is loaded into the prepared base, mixed and cooled to room temperature. The result is a suspension with a synthetic tannin content of 5.1 wt. % and polidocanol 5.0 wt. %.

Composition in the form of a solution.

Example 16

The required amount of base to obtain a solution is melted at a temperature of 72°C, mixed and filtered. The calculated amount of synthetic tannin and polidocanol is loaded into the prepared base, mixed and cooled to room temperature. The result is a solution with a synthetic tannin content of 5.1 wt. % and polidocanol 5.0 wt. %.

Example 17.

The required amount of base to obtain a solution is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and anesthesin is loaded into the prepared base, mixed and cooled to room temperature. The result is a solution with a synthetic tannin content of 0.1 wt. % and anesthesin 0.1 wt. %.

Example 18.

The required amount of base to obtain a solution is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and dikain is loaded into the prepared base, mixed and cooled to room temperature. The result is a solution with a synthetic tannin content of 6.1 wt. % and dicaine 0.1 wt. %.

Example 19.

The required amount of base to obtain a solution is melted at a temperature of 72°C, mixed and filtered. The calculated amount of synthetic tannin and lidocaine is loaded into the prepared base, mixed and cooled to room temperature. The result is a solution with a synthetic tannin content of 3.1 wt. % and lidocaine 9.1 wt. %.

Example 20.

The required amount of base to obtain a solution is melted at a temperature of 70°C, mixed and filtered. The calculated amount of synthetic tannin and pyromecaine is loaded into the prepared base, mixed and cooled to room temperature. The result is a solution with a synthetic tannin content of 5.9 wt. % and pyromecaine 6.4 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.

The purpose of experimental laboratory studies was to evaluate the intrinsic antimicrobial activity (antimicrobial activity) of the claimed composition against 5 microorganisms: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus cereus and Candida albicans; anti-inflammatory (decongestant) action of the claimed composition. Clinical and laboratory studies of the proposed composition were also carried out with the determination of the pigmentometry index (according to the vascular type), reflecting the degree of skin erythema.

Below is an assessment of the intrinsic antimicrobial activity (antimicrobial action) of the proposed composition against 5 microorganisms: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus cereus and Candida albicans using a suspension as an example. Studies were carried out on test strains of the following types of microorganisms: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538-P, Pseudomonas aeruginosa ATCC 9027, Bacillus cereus ATCC 10702, Candida albicans ATCC 885-653. Own antimicrobial activity was determined once.

Cultures of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus cereus were cultivated in meat-peptone broth at 37°C for 19 hours. Candida albicans was cultivated in meat-peptone broth at 37°C for 19 hours. Candida albicans was cultured in liquid Sabouraud medium at 30°C for 48 hours. From each grown culture, a suspension of microorganisms was prepared in physiological saline in a ratio of 1:1000. In 10 ml of a buffer solution consisting of monosubstituted potassium phosphate and disubstituted sodium phosphate in physiological saline, 1 ml was added from the microbial suspension and the first dilution of the suspension. Test tubes with nutrient media and the corresponding test strains served as controls, in which the same amount of sterile distilled water was added instead of the tested cosmetics. The crops were incubated at 30°C for 48 hours (fungi for 7 days). After the expiration of the incubation period, from the control tubes and test tubes with the introduction of the test agent, seedings were made on the appropriate selective media: Escherichia coli - on Endo medium, Staphylococcus aureus - on yolk-salt agar, Pseudomonas aeruginosa - on nutrient agar for Ps.aeruginosa, Bacillus cereus - on nutrient agar, Candida albicans on chromogenic agar for Candida fungi.

The results of the studies (table 1) showed that the analyzed suspension has its own antimicrobial activity against all studied test strains of microorganisms: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus cereus and Candida albicans.

In the control tubes, in the absence of the test agent, subject to all other conditions, there was an increase in all of the above test strains of microorganisms.

Below are the data of the study of anti-inflammatory (decongestant) action of the claimed composition on the example of a cream.

Experimental studies were carried out on 30 white rats, males, Wistar line, weighing 230-250 g, which are in the standard vivarium mode. 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 compositions.

The determination of the anti-inflammatory effect was carried out according to the method of F.P. Trinus et al., creating a model of experimental inflammation (edema) by subplantar injection of 1% formalin solution in an amount of 0.1 ml into one of the hind legs of rats. An increase in paw volume was recorded in dynamics every hour from the moment of development of inflammation and application of the studied extract for three hours and after 24 hours (day). Intact animals served as controls, on the skin of which nothing was applied after the development of the focus of inflammation, and in them the process of rehabilitation of inflammation occurred spontaneously. The volume of the inflamed rat paw was measured using a flexible millimeter tape. The percentage of inhibition of inflammation was calculated according to the formula defined in this method.

When evaluating the results obtained, it was noted that the claimed composition (cream) has a pronounced anti-inflammatory effect: after 1 hour it was 23.9%, after 2 hours the effect remained at the same level and also amounted to 23.9%. After 3 hours, the anti-inflammatory effect increased and reached 37.9%. A day after its application, the anti-inflammatory effect was significant, maximum and amounted to 90.0% (Fig. 1).

In order to assess the clinical efficacy of the claimed composition, objective studies were carried out, with the determination of the pigmentometry index (according to the vascular type), reflecting the degree of skin erythema, on the Multi Skin Test Center® MC 750 device, manufactured by Courage + Khazaka electronic GmbH (Germany) .

Clinical studies of the claimed composition were conducted on 30 women, aged 40 to 65 years.

Measurements of indicators of the degree of erythema were carried out at the same time of 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. The measurement area for each probant before and after application of the claimed composition was the same, at a strictly defined point, which is reflected in the protocol cards for each patient.

The specialists who conducted clinical studies, as well as the probants themselves, noted that the claimed composition has a uniform delicate texture, is easily and evenly applied to the skin, is well absorbed, and does not have an irritating and allergenic effect. All volunteers after its application noted good tolerability.

To assess the effectiveness of the claimed composition in relation to the level of erythema, all volunteers were artificially induced erythema in the forearm area, using a source of UV radiation (simulator), widely used in specialized cosmetology centers - a mini-tanning bed of the Dr.Kern trademark with a halogen emitter and wavelength in the range from 290 to 400 nm, manufactured by Kern GmbH (Germany).

The results of the study on assessing the level of pigmentometry by vascular type showed that under the action of the claimed composition in the form of a solution, the level of erythema statistically significantly decreased after its application by 16.4% compared with the initial level (Fig. 2), which indicates the effectiveness of the composition in relation to reduce the level of erythema (redness) of the skin.

The results of the study on the assessment of the level of erythema under the action of the claimed composition in the form of a cream showed that the level of erythema in this case statistically significantly decreased somewhat more than in the previous one and corresponded to 18.5% compared to the initial level (Fig. 3), which also indicates its effectiveness in reducing the level of erythema (redness) of the skin.

When analyzing the results of assessing the erythema index under the action of the claimed composition in the form of a suspension, it was found that after its application, the level of erythema statistically significantly decreased by 22.3% compared with the initial level (Fig. 4), which indicates effectiveness in reducing the level of erythema (redness) of the skin.

Thus, the analysis of experimental laboratory and clinical laboratory data in dynamics gives grounds to draw the following conclusion that the claimed composition for complex skin care in the treatment of dermatoses is effective, well tolerated by patients, does not have negative side effects, has antimicrobial activity and anti-inflammatory action.

Claims (12)

1. Composition for complex skin care in the treatment of dermatosis, containing synthetic tannin and a base, characterized in that it additionally contains a local anesthetic component selected from the group: dikain, polidocanol, anesthesin, pyromecaine, lidocaine, with the following content of components, wt. %: Synthetic tannin - 0.1-10.0 Local anesthetic component selected from the group: dicaine, polidocanol, anesthesin, pyromecaine, lidocaine - 0.1-10.0 Base - up to 100. 2. The composition according to claim. 1, characterized in that as a base it contains an acceptable base, allowing it to be made in the form of a cream. 3. The composition according to claim 2, characterized in that the acceptable base contains water, an emulsifier, an emollient, a stabilizer, a film former, a preservative, a thickener. 4. The composition according to claim 1, characterized in that it contains a suitable base as a base, allowing it to be made in the form of a suspension. 5. The composition according to claim 4, characterized in that the acceptable base contains water, a film former, a thickener, an emulsifier, an emollient, a preservative, a gel former. 6. The composition according to claim. 1, characterized in that it contains an acceptable base as a base, allowing it to be made in the form of a solution. 7. Composition according to claim 6, characterized in that the acceptable base contains water and a preservative. 8. Composition according to claim 6, characterized in that a certain amount of the solution can be placed in a spray bottle.

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