RU2737268C1 - Cosmetic and / or pharmaceutical composition for treating skin diseases - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to treatment of skin diseases. Pharmaceutical composition for external use for treating skin diseases contains 1.0-5.0 wt% of poly-N,N-dialkyl-3,4-dimethylene-pyrrolidinium of halide of general formula

(I),

in which R¹ and R² denote, independently, a linear or branched alkyl with 1-6 carbon atoms, and X denotes fluorine, chlorine, bromine, tetraborate or tetrafluoroborate, Y denotes iodine, wherein the average molecular weight of the poly-N,N-dialkyl-3,4-dimethylene-pyrrolidinium of halide ranges from 500 to 1000000, 1.0-5.0 wt% methylsulphonylmethane, the rest is an acceptable carrier. Also disclosed is another version of the composition, use of compositions for treating autoimmune skin diseases, microbial, viral, fungal and parasitic skin diseases, and household burn wounds, cut and chemical wounds, gunshot and broken wounds, postoperative and post-traumatic wounds, insect bites, itching.

EFFECT: group of inventions provides higher antimicrobial effectiveness with anti-inflammatory and wound-healing action.

15 cl, 1 tbl, 12 ex

Description

The invention relates to the field of medicine and cosmetology, in particular to a cosmetic and / or pharmaceutical composition for external use for the treatment of diseases of the skin, containing poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide, methylsulfonyl methane and an acceptable carrier.

The urgency of the problem of skin diseases is constantly increasing. The number of patients with skin diseases of an allergic nature, with tumor processes of the skin, autoimmune diseases is constantly growing, the growth of parasitic and fungal diseases does not decrease. The main factors affecting their development include constantly worsening environmental conditions, harmful production conditions, disorders of the nervous system and the endocrine gland system, genetic disorders, harmful mutations, malnutrition and malnutrition, viral infections, constant stress, lack of eating vitamins, non-compliance with personal hygiene rules. As a rule, existing medicinal and cosmetic products are narrowly targeted in application. Effective drugs from among them, for the most part, contain antibiotics or steroid hormonal drugs as active components, which can cause side effects.

A number of antiseptic preparations for the treatment of skin integuments, made in various forms (cream, gel, etc.) containing polyethylene pyrrolidinium chloride, are known from the prior art. The specified compound can be present in the composition of these preparations as a synergist for the main disinfectant component of the compositions - the polyguanidine compound. Moreover, the use of a relatively high molecular weight polyethylene pyrrolidinium chloride (50-100 thousand) is aimed at reducing the share of more expensive polyguanidine while maintaining high biocidal activity. Also in these works, a low biocidal activity of polyethylene pyrrolidinium chloride is noted. These compositions exhibit only a disinfecting effect and cannot act as a cosmetic or drug that exhibits anti-inflammatory and wound healing effects, and at the same time is capable of relieving symptoms of irritated skin such as redness, itching, peeling, etc.

From the patent RU 2272045 a disinfectant is known containing poly (diallylmethylammonium trifluoroacetate) or poly (diallylammonium trifluoroacetate) with a molecular weight of 24000-65000 g / mol, and having a high bactericidal and fungicidal activity. However, due to the high aggressiveness of trifluoroacetate, this agent could hardly find application in products used on the skin.

Also from the prior art (RU 2694758) an antimicrobial composition is known containing a chelating agent or its salts, a transport enhancer and an acceptable carrier or base for such compositions, and the chelating agent and transport enhancer are present in the composition in an amount and ratio effective to ensure a significant reduction of bacterial and / or fungal biofilms on the surface treated with said composition; and the content of the chelating agent in the composition is from about 0.1% (w / w) to about 15% (w / w), the content of the transport enhancer in the composition is from about 0.1% (w / w) to about 40% ( w / w), wherein the transport enhancer is methylsulfonylmethane (MSM) and the ratio of chelating agent to methylsulfonylmethane is from about 10: 1 to about 1:20. However, the principle of action of this composition is based only on the chelating blocking of the supply of metal ions necessary for the vital activity of bacteria and fungi, and therefore has a very limited field of application; to create a more universal action, the inventors add additional antibiotics to the composition. Also, this composition shows only an antiseptic effect and does not have an anti-inflammatory and healing effect in diseases of the skin.

The closest analogue should be considered a cosmetic and / or pharmaceutical composition disclosed in patent RU 2408380, which, in combination with suitable carriers for external use, is suitable for the treatment of inflammatory skin diseases, and includes a mixture consisting of methylsulfonylmethane and at least one compound belonging to the class of 4-alkylcyclohexanols, wherein said at least one compound belonging to the class of 4-alkylcyclohexanols is 4-tert-butylcyclohexanol. This composition is aimed at counteracting the inflammatory processes of the skin, in which there is an increased production of chemical inflammatory mediators and activation of TRPV membrane receptors, and due to its ability to inhibit the activation of TRPV receptors, it significantly reduces the intensity of many uncomfortable sensations, such as, for example, burning and itching. However, this composition has no antiseptic effect, and requires the use of additional disinfectants before applying the composition to the skin to remove the microorganisms present.

Therefore, the object of the present invention was to create new cosmetic and / or pharmaceutical compositions having increased antimicrobial efficacy, and at the same time exhibiting anti-inflammatory and wound healing effects, as well as being able to reduce the intensity of skin discomfort, such as, for example, redness, itching, burning, flaking etc.

The problem was solved by developing a new cosmetic and / or pharmaceutical composition for external use for the treatment of diseases of the skin, containing

1.0-5.0% of the mass. poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide of general formula (I):

(I),

(I),

wherein

R ¹ and R ^{2 are,} independently of each other, linear or branched alkyl having 1-6 carbon atoms, and

X means the anion of fluorine, chlorine, bromine, tetraborate or tetrafluoroborate,

Y stands for iodide ion,

moreover, the average molecular weight of the poly-N, N-dialkyl-3,4-dimethylene-pyrrolidinium halide is from 500 to 1,000,000,

1.0-5.0% of the mass. methylsulfonylmethane,

the rest of the acceptable carrier (base).

The specified cosmetic and / or pharmaceutical composition provides a primary antimicrobial treatment of wounds, and at the same time exhibits a long-term anti-inflammatory and wound healing effect, and also reduces the intensity of discomfort of the skin, such as, for example, redness, itching, burning, peeling, etc.

Poly-N, N-dimethyl-3,4-dimethylenepyrrolidinium halide - structurally similar to natural compounds (proline and hydroxyproline), in fact, a "quasi-charged" protein suppresses the activation of macrophages, inhibits excessive synthesis of cytokinites, blocking the transmission of a signal to tissues about inflammation. At the same time, it is an antimicrobial agent with a wide spectrum of action against bacteria, viruses, fungi, microorganisms, parasites, a synergist for other components in all compositions, and normalizes metabolic processes. These compounds, being cationic-anionic, complexing, charged polymers, recharge and destroy the structure of the extracellular polymeric substance formed by microorganisms on the surface of the affected area, thereby making them available for action as poly-N, N-dimethyl-3,4-dimethylenepyrrolidinium halides and other components of the compositions.

The use of a copolymer containing iodide ions increases the antimicrobial effect of poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium halide in comparison with a homopolymer, for example chloride, this is due to the special action of the iodine anion in the polymer matrix. Considering that chlorine, entering into a reaction, is more strongly bound to the surface layers of protoplasm, then iodine, being in the matrix of poly-N, N-dimethyl-3,4-dimethylenepyrrolidinium halide, weakly binding to protein, easily penetrates into the microbial cell ... It is known that the antimicrobial effect of iodine in combination with a carrier is several times greater than the bactericidal properties of chlorine.

According to the invention, the radicals R ¹ and R ² in the formula (I) are, independently of one another, linear or branched alkyl having 1-6 carbon atoms. In a preferred embodiment of the invention, the radicals R ¹ and R ² in formula (I) are independently methyl, ethyl, propyl or butyl. It is particularly preferred that R ¹ and R ² are the same and are methyl.

According to the invention, in poly-N, N-dialkyl-3,4-dimethylenepyrrolidinium halide, the anion X ^- is fluorine, chlorine, bromine, tetraborate or tetrafluoroborate ions, and the anion Y is iodide ion, and the molar ratio of X and Y in the polymer can vary from 1:99 to 99: 1.

In a preferred embodiment, the iodide ion content is up to 30 mol%, based on the total content of the anions X and Y, preferably the iodide ion content is from 1 to 30 mol%, particularly preferably from 10 to 30 mol%, most preferably 10 to 20 mol%, based on the total content of X and Y anions.

In a particularly preferred embodiment, the poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide is poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium chloride iodide.

In a most preferred embodiment, the poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide is poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide (II), which is a copolymer of N, N-dimethyl -N, N-diallylammonium chloride and N, N-dimethyl-N, N-diallylammonium iodide, and the ratio of n and m in the polymer can vary from 1:99 to 99: 1.

(II)

(Ii)

According to the invention, the average molecular weight of the poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide is from 500 to 1,000,000, preferably from 1,000 to 500,000, particularly preferably from 10,000 to 100,000 and most preferably from 10,000 to 26,000.

The composition according to the invention contains from 1.0-5.0% of the mass. poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide of general formula (I).

According to the invention, the composition also contains methylsulfonylmethane, also called organic sulfur. This compound has anti-inflammatory and antioxidant effects, participates in the synthesis of keratin, collagen, which promotes the renewal of skin cells, has analgesic properties, provides flexibility and mobility of tissues, and, like dimethyl sulfoxide, can act as a transport enhancer.

The combined use of poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide with methylsulfonylmethane (MSM) also gives a synergistic effect in terms of antimicrobial activity, since in the composition according to the invention poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium halide when interacting with MSM forms a complex (III):

(III)

(III)

This complex allows you to significantly increase the speed of exposure of the composition to damaged areas of the skin.

The amount of methylsulfonylmethane in the composition according to the invention is in the range from 1.0 to 5.0% of the mass.

As a carrier, ointments on lipophilic, hydrophilic, lipophilic-hydrophilic bases, gels, cream bases, liniment, emulsions, aqueous solutions and powders can be used.

Also, the authors of the invention have found that if unsaturated dicarboxylic acid, or its esters or salts, respectively, is introduced into the composition of the previously described composition, then its therapeutic effect on the manifestations of diseases such as psoriasis and various types of dermatitis increases significantly, which is expressed in a rapid decrease in the severity of inflammatory processes and the onset of remission.

Therefore, another object of the invention is a cosmetic and / or pharmaceutical composition for external use for the treatment of diseases of the skin, containing

1.0-5.0% of the mass. poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide of general formula (I):

(I),

(I),

wherein

R ¹ and R ^{2 are,} independently of each other, linear or branched alkyl having 1-6 carbon atoms, and

X means the anion of fluorine, chlorine, bromine, tetraborate or tetrafluoroborate,

Y stands for iodide ion,

moreover, the average molecular weight of the poly-N, N-dialkyl-3,4-dimethylene-pyrrolidinium halide is from 500 to 1,000,000,

1.0-5.0% of the mass. methylsulfonylmethane,

0.5-3.0% of the mass. unsaturated dicarboxylic acid selected from maleic acid, fumaric acid and itaconic acid, or their esters or salts, respectively,

the rest of the acceptable carrier (base).

According to the invention, the unsaturated dicarboxylic acid is selected from maleic acid, fumaric acid and itaconic acid, and esters and salts of these acids are also suitable.

In one embodiment, the composition according to the invention preferably comprises maleic acid diethyl ester, maleic acid dimethyl ester or maleic acid disodium salt.

These compounds are active substances capable of suppressing the putative autoantigen of psoriasis.

In another preferred embodiment, the composition according to the invention contains itaconic acid or dimethyl itaconate.

Itaconates inhibit the activation of macrophages, are able to bind to regions of protein molecules that carry sulfur and hydrogen atoms in thiol groups - SH, are able to suppress inflammation reactions by acting on various biochemical pathways, and alleviate the symptoms of autoimmune diseases arising from excessive activity of inflammatory processes, for example , with psoriasis.

The content of unsaturated dicarboxylic acid or, respectively, its ester or salt in the cosmetic and / or pharmaceutical composition according to the invention can be from 0.5 to 3.0% of the mass.

In the composition of the compositions according to the invention, vitamin A (retinol), vitamin E (tocopherol), vitamins of group B (B1, B6, PP, B12), vitamin D, succinic acid or its salts, boric acid, compounds zinc, magnesium, lanthanum, silver, gold.

These additional substances can be contained in the compositions according to the invention in amounts from 0.001 to 1% of the mass.

To enhance the therapeutic effect, medicinal substances belonging to the following pharmacological groups can be introduced into the compositions:

- Metabolics (antioxidants, vitamins and vitamin-like agents, macro and microelements), antimicrobial, antiparasitic and antihelminthic agents (antibiotics, antiseptics and disinfectants, antifungal agents, antiparasitic agents, synthetic antibacterial agents), hormones, homeopathic remedies, regenerants and reparants agents (anticoagulants, coagulants, hemostatics), neurotropic agents (local anesthetics, local irritants, adaptogens).

- Adaptogens: products containing ginseng, Eleutherococcus, Rhodiola rosea, sea buckthorn, astragalus, aralia, Peruvian poppy seeds, lemongrass, centaury, mummy, humic substances (humic and sulfic acids) pantocrine, bee waste products.

- Local irritants containing essential oils of peppermint leaves, menthol, validol, plantain juice, etc.

Also, in the manufacture of compositions to increase efficiency and improve consumer properties, additional compatible chelating agents of various natures, glucose and its isomers, cyclodextrins (cyclic glucose oligomers), disaccharides, polysaccharides, PEGs (polyethylene glycols), which are approved for use in the pharmaceutical and cosmetic industries, can be used, PEO (polyethylene oxides), polyhydric alcohols (glycerin, etc.), swellable hydrophilic polymers, cellulose polymers, buffering agents and preservatives, stabilizers, fragrances, emulsifiers, etc. At the same time, the use of preservatives, emulsifiers, chelating agents is not necessary, since poly-N, N-dimethyl-3,4-dimethylenepyrrolidinium halide itself is a universal preservative and acts as an emulsifier and chelating agent.

The compositions of this invention also include pharmaceutically acceptable carriers, depending on the particular type of preparation. For example, the composition of this invention can be in the form of a solution, suspension, paste or gel, in which case the carrier is at least partially aqueous. Therefore, the compositions according to the invention can also contain water in an amount from 0.1 to 97.5% of the mass.

The compositions of this invention may be in the form of an ointment, in which case the pharmaceutically acceptable carrier consists of an ointment base. Preferred ointment bases according to the present invention have a melting or softening point close to body temperature; preferably ointment bases contain petrolatum and mixtures of petrolatum and mineral oil. Preferably, the content of the ointment base, in particular petrolatum or a mixture of petrolatum and mineral oil, in the composition according to the invention is from 50 to 98 wt%. particularly preferably from 77 to 97.5% of the mass.

The compositions according to the invention can be used both independently and as part of complex therapy in the treatment of autoimmune skin diseases (dermatoses, psoriasis, neurodermatitis, etc.), microbial skin diseases (furunculosis, granulomatosis, acne, etc.), viral (herpes, papillomas, warts, shingles, etc.), fungal and parasitic (candidiasis, seborrhea, scabies, etc.) skin diseases. Also, the compositions according to the invention have a high hemostatic effect, are effective in the treatment of domestic burn wounds, cut and chemical wounds, gunshot and stab wounds, postoperative and post-traumatic wounds, insect bites, itching, including that observed in patients with diabetes mellitus, helps to restore the skin without the formation of pronounced scar tissue.

The invention is illustrated in more detail by the following examples.

EXAMPLES

Examples of the preparation of compositions according to the invention

In the examples of the preparation of the compositions according to the invention, poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide obtained by copolymerization of N, N-dimethyl-N, N-diallylammonium chloride and N, N-dimethyl-N, N-diallylammonium iodide in various ratios (from 9: 1 to 7: 3), and the resulting polymers had an average molecular weight of 20,000 to 26,000.

Example 1. Preparation of a composition according to the invention in the form of an ointment

25 g of poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide in the form of a crushed dry powder or crystals are dissolved in 45 ml of distilled water at a temperature of 60 ° C. To the resulting viscous solution add 25 g of methylsulfonylmethane also dissolved at 60 ° C in 55 ml of distilled water. The resulting solution is thoroughly mixed and in equal portions for 30-40 minutes is fed into the medical petroleum jelly (850 g) melted in a water bath with constant stirring and maintaining the temperature of the molten petroleum jelly. After the introduction with constant stirring, the mixture is cooled to room temperature. The result is an ointment with a uniform consistency from white to light yellow (depending on the color of the medical petroleum jelly used) in the amount of 1000 g.

Example 2. Preparation of a composition according to the invention in the form of a gel

3.0 g of CELLOSIZE ™ hydroxyethyl cellulose is dispersed in 847 ml of distilled water at a temperature of 40-60 ° C. The result is a thick, highly viscous transparent gel. Further, similarly to Example 1, 25 g of poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide in the form of crushed dry powder or crystals are dissolved in 45 ml of distilled water at a temperature of 60 ° C. To the resulting viscous solution add 25 g of methylsulfonylmethane also dissolved at 60 ° C in 55 ml of distilled water. The resulting solution is thoroughly mixed and served in equal portions for 30-40 minutes into the prepared gel with slow stirring. The process takes place at room temperature. The result is a translucent gel of the desired viscosity in the amount of 1000 g.

Example 3. Preparation of a composition according to the invention containing a disodium salt of maleic acid in the form of an ointment

25 g of poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide in the form of a crushed dry powder or crystals are dissolved in 45 ml of distilled water at a temperature of 60 ° C. Next, to the resulting viscous solution, 25 g of methylsulfonylmethane dissolved at 60 ° C in 55 ml of distilled water and 7.0 g of disodium salt of maleic acid dissolved at 60 ° C in 70 ml of distilled water are successively added. The resulting solution is thoroughly mixed and in equal portions for 50-60 minutes is fed into the medical petroleum jelly (773 g) melted in a water bath with constant stirring and maintaining the temperature of the molten petroleum jelly. After addition, with constant stirring, the mixture cools to room temperature. The result is an ointment with a uniform consistency from white to light yellow (depending on the color of the medical petroleum jelly used) in the amount of 1000 g.

Example 4. Preparation of a composition according to the invention containing retinol and tocopherol in the form of an ointment

25 g of poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide in the form of a crushed dry powder or crystals are dissolved in 45 ml of distilled water at a temperature of 60 ° C. To the resulting viscous solution is added a mixture of 25 g of methylsulfonylmethane dissolved at 60 ° C in 55 ml of distilled water. The resulting solution is thoroughly mixed and in equal portions for 30-40 minutes is fed into the medical petroleum jelly (828 g) melted in a water bath with constant stirring and maintaining the temperature of the molten petroleum jelly. Next, 2 ml of the finished form of Alpha tocopherol acetate 300 mg / ml (0.6 g of tocopherol) and 20 ml of the finished form of retinol palmitate 100,000 IU / ml (0.6 g of retinol) are added sequentially for 10 minutes. After the introduction with constant stirring, the mixture is cooled to room temperature. The result is an ointment with a uniform consistency from white to light yellow (depending on the color of the medical petroleum jelly used) in the amount of 1000 g.

By analogy with example 1, compositions were obtained in the form of an ointment containing poly-N, N-dimethyl-3,4-dimethylenepyrrolidinium chloride-iodide from 1 to 5% of the mass. (Examples 5-8).

Table 1. Composition of compositions according to the invention (in% wt.) Obtained in examples 1-8

Composition of the composition Etc. 1 Etc. 2 Etc. 3 Etc. 4 Etc. five Etc. 6 Etc. 7 Etc. eight Polymer ¹ 2.5 2.5 2.5 2.5 1.0 1.5 5.0 2.5 MSM ² 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 Disodium salt of maleic acid - - 0.7 - Petrolatum 85.0 77.3 84.78 86.5 86.0 82.5 85.0 Hydroxyethyl cellulose 0.3 - - - - - - Water 10.0 94.7 17.0 10.0 10.0 10.0 10.0 10.0 Retinol palmitate (0.6 g retinol) 0.2 Tocopherol acetate (0.6 g tocopherol) 0.02 Content of iodide ion ³ ten ten ten 20 ten thirty ten thirty

¹ Poly-N, N-dimethyl-3,4-dimethylenepyrrolidinium chloride iodide,

² Methylsulfonylmethane,

³ Content of iodide ion (% wt.) In poly-N, N-dimethyl-3,4-dimethylenepyrrolidinium chloride iodide, in terms of the total content of chlorine and iodine anions.

Examples of the use of the compositions according to the invention for the treatment of diseases of the skin

Example 9

Patient U, 23 years old.

Suffering from neurodermatitis for five years. Remissions are replaced by relapses after 3-4 months.

The disease is of a limited form (limited areas of dry, rough, infiltrated skin with soft pityriasis peeling and a sharply emphasized pattern of skin furrows). Skin coloration is pale pink with a yellowish tint, in places reddish with a bluish tinge. The patient has lesions on the back and side of the neck, in the area of the elbow and popliteal folds. Against this background, small papules, brownish crusts are periodically poured out, pigmentation along the periphery. After applying the ointment, the severity of symptoms of skin lesions and itching dynamically disappears or sharply decreases. The period of remission increases.

Compositions were used during relapse periods with the content of poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide 1.0%, 2.5%, 5% (according to examples 5, 1 and 7, respectively) on various skin areas. When using the compositions with a concentration of 2.5% and 5%, the effect of the application was identical and stronger in terms of the speed of exposure and the establishment of remission than when using the composition with 1%.

Example 10. Patient Y. 50 years old. Diagnosis of psoriasis.

Compositions prepared according to example 1 and example 3 were used for treatment.

Has been sick for 8 years. The disease progresses with a sharp deterioration in the winter season. After applying the ointment, applied in a uniform thin layer to the affected surface, there is a characteristic weakening of the color intensity and infiltration of the rashes, some of which gradually dissolve. The dissolution of plaques began from the peripheral areas, the psoriatic elements (papules) seemed to melt, and a white depigmented corolla formed around them, and temporary depigmentation remains in the places of the resolved rashes. During the period of the process subsiding on some areas of the skin of the elbows, knee joints, there were isolated "duty" plaques. Treatment is indicated in winter, since this patient has psoriasis according to seasonality in winter.

The compositions were applied during periods of relapse with a 2.5% poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide content on various skin areas. When using a composition containing a disodium salt of maleic acid (example 3), the resorption of plaques began on the second day of application, the itching disappeared within an hour after application. When using the composition without disodium salt of maleic acid (example 1), these effects occurred on the third or fourth day of systematic use of the ointment.

Example 11. Patient E., 40 years old, complained of sudden redness and swelling in the area of the hands and forearms, the appearance of bubbles in these areas of the skin. Burning and itching in the area of the hands. He considers the reason for harvesting weeds in the country is milkweed with his bare hands.

Diagnosis: acute dermatitis.

After applying the ointment containing poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide in 2.5% (example 4) twice a day, the swelling completely disappeared on the second day, the itching became less intense and disappeared after three days ... By the end of the week, dry crusts formed in place of the bubbles, and when they fell away, bluish-pink spots were visible in their place for several days.

Example 12. Patient C. 35 years old. Diagnosis - Erythrasma.

In the area of the inner surfaces of the thighs in the upper third and with the transition to the inguinal folds, non-inflammatory spots of brick-red, in places light brown with sharp contours are visible. Minor itching occasionally worries.

Used compositions containing poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride iodide 1.5% (example 6) and 2.5% (example 8), on the affected skin on the right and left sides, respectively.

After rubbing the ointment on the affected areas every day, 1-2 times a day after 3 days, the spots on the left side disappeared completely, while on the right side there was a residual lesion, especially pronounced in the groin fold. To treat the affected area, an ointment with a content of 2.5% was replaced. On the second day of application, the same result was achieved as on the left side. It is recommended to periodically rub the ointment into problem areas of the skin for 2-3 weeks in order to prevent relapse.

Thus, the presented examples of use show the high efficiency and versatility of the compositions according to the invention in the treatment of a wide range of diseases of the skin, while exhibiting increased antimicrobial efficacy and anti-inflammatory effects, and reducing the intensity of skin discomfort, such as, for example, redness, itching, burning and peeling.

Claims (34)

1. Pharmaceutical composition for external use for the treatment of diseases of the skin, containing 1.0-5.0 wt.% Poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide of the general formula

(I), wherein R ¹ and R ^{2 are,} independently of one another, linear or branched alkyl having 1-6 carbon atoms, and X stands for fluorine, chlorine, bromine, tetraborate or tetrafluoroborate, Y means iodine, moreover, the average molecular weight of the poly-N, N-dialkyl-3,4-dimethylene-pyrrolidinium halide is from 500 to 1,000,000, 1.0-5.0 wt.% Methylsulfonylmethane, the rest is an acceptable carrier (base). 2. Composition by. 1, characterized in that R ¹ and R ² in formula (I) independently of one another mean methyl, ethyl, propyl and butyl. 3. Composition by. 1, characterized in that R ¹ and R ² in formula (I) are the same and are methyl. 4. Composition by. 1, characterized in that in poly-N, N-dialkyl-3,4-dimethylenepyrrolidinium halide, the iodide ion content is up to 30 mol%, based on the total content of X and Y anions. 5. Composition by. 4, characterized in that the iodide ion content is from 10 to 20 mol.%, Based on the total content of the X and Y anions. 6. Composition by. 1, characterized in that the poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide is poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium chloride iodide. 7. Composition by. 1, characterized in that poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide is poly-N, N-dimethyl-3,4-dimethylene pyrrolidinium chloride-iodide, which is a copolymer of N, N-dimethyl-N, N-diallylammonium chloride and N, N-dimethyl-N, N-diallylammonium iodide. 8. Composition by. 1, characterized in that it additionally contains at least one of the components of the group including vitamin A (retinol), vitamin E (tocopherol), vitamins of group B, in particular B1, B6, PP, B12, vitamin D, succinic acid or its salts, boric acid, compounds of zinc, magnesium, lanthanum, silver or gold. 9. Pharmaceutical composition for external use for the treatment of diseases of the skin, containing 1.0-5.0 wt% poly-N, N-dialkyl-3,4-dimethylene pyrrolidinium halide of the general formula

(I), wherein R ¹ and R ^{2 are,} independently of each other, linear or branched alkyl having 1-6 carbon atoms, and X means fluorine, chlorine, bromine, tetraborate or tetrafluoroborate, Y means iodine, moreover, the average molecular weight of the poly-N, N-dialkyl-3,4-dimethylene-pyrrolidinium halide is from 500 to 1,000,000, 1.0-5.0 wt% methylsulfonylmethane, 0.5-3.0 wt% of an unsaturated dicarboxylic acid selected from maleic acid, fumaric acid and itaconic acid, or their esters or salts, respectively, the rest is an acceptable carrier (base). 10. Composition by. 9, characterized in that it contains diethyl ester of maleic acid or disodium salt of maleic acid as an unsaturated dicarboxylic acid or its ester or salt. 11. Composition by. 9, characterized in that it contains itaconic acid or dimethyl itaconate as an unsaturated dicarboxylic acid or its ester or salt. 12. Composition by. 9, characterized in that it additionally contains at least one of the components of the group including vitamin A (retinol), vitamin E (tocopherol), vitamins of group B, in particular B1, B6, PP, B12, vitamin D, succinic acid or its salts, boric acid, compounds of zinc, magnesium, lanthanum, silver or gold. 13. The use of the composition according to PP. 1-12 for the treatment of autoimmune skin diseases, microbial, viral, fungal and parasitic skin diseases. 14. Use according to claim 13 for the treatment of dermatoses, psoriasis, neurodermatitis, furunculosis, granulomatosis, acne, herpes, papillomas, warts, shingles, candidiasis, seborrhea and scabies. 15. The use of the composition according to PP. 1-12 for the treatment of household burn wounds, cut and chemical wounds, gunshot and stab wounds, postoperative and post-traumatic wounds, insect bites, itching.