EA017660B1 - Antiinflammatory and antiallergic gel - Google Patents

Abstract

The invention relates to medicine, namely to creation of medicinal composition in the form of gel for external application, having an antiinflammatory and antiallergic effect, which can be widely used as a first aid means for treating antiinflammatory and antiallergic skin diseases, burn of I-II degrees, blood-sucking insects, itching, bruises, scratches, contusions, etc for treating vasomotor and allergic rhinitis, as well as inflammatory diseases of eyes with allergic manifestations. Gel possessing antiinflammatory and antiallergic effect is characterized in that it comprises as active substance N-(β-oxyethyl)-4,6-dimethyldihydropirimidone-2 (xymedone) and as an antihistamine preparation diphenhydramine, or clemastine, or cetiresine and a gel base comprising carbopol as a thickener and also polyethylenoxide with molecular weight 400-6000 Da, 0-20.0 mass% glycerin, 0.41 mass% ethyl alcohol and purified water with the following ratio components, mass%: xymedone - 3-10; said antihistamine preparation – 0.005-1.0; carbopol – 0.5-1.0; said polyethylenoxide – 0.5-1.0; glycerin - 0-20.0; ethyl alcohol - 0-41; purified water - the rest to 100. The gel can further comprise mentholin an amount not exceeding 0.5% of the total mass and also a preservative, a stabilizer and a neutralizing agent. Nipagin or benzalkonium chloride are used as the preservative, Trilon B or Tvin-80, or a mixture of Trilon B and gentamicin sulfate, or a mixture of Tvin-80 and polyethylenoxide 400 are used as the stabilizer. Sodium hydroxide, or an ammonia-water mixture, or trometamol are used as the neutralizing agent.

Description

The invention relates to medicine, namely to the creation of a medicinal composition in the form of a gel for external use with anti-inflammatory and anti-allergic effects, which can be widely used for the treatment of inflammatory and allergic skin diseases, burns Ι-ΙΙ degrees, bites of blood-sucking insects, itching, bruises , abrasions, bruises, etc., for the treatment of vasomotor and allergic rhinitis, as well as for the treatment of inflammatory eye diseases with allergic manifestations.

In the structure of skin pathology, allergic skin diseases dominate. Allergic dermatosis affects up to 15% of the world's population. Data from various researchers indicate not only a significant increase in the number of patients (an average of 5% annually), but also an increase in the severity of allergic skin diseases. A clear tendency towards an increase in severe clinical forms leading to disability, a tendency toward dissemination of skin rashes, frequent relapses, and a low percentage of recovery raise the problem of treating allergic skin pathologies as one of the first places in modern clinical medicine. In this regard, the creation of medicines for the treatment of acute and chronic dermatoses is of particular importance. Pathogenetically substantiated and effective in the treatment of allergic dermatoses is glucocorticoid therapy. Glucocorticoids exert a complex multilateral effect on the body. On the one hand, they have strong anti-inflammatory activity, which is difficult to compete with other drugs, on the other hand, they have immunosuppressive properties, which is the result of the suppression of various stages of immunogenesis.

Betamethasone (9-fluoro-11 ^₽ , 17,21-trihydroxy-16 ^₽- methylpregn-1,4-diene-3,20-dione-17,21 dipropionate) - fluorinated synthetic glucocorticoid is one of the most effective drugs in this group [Mashkovsky M.D. Medicines, vol. 2, ed. 13th Kharkov: Torsing, 1997, p. 38]. Betamethasone has a pronounced anti-inflammatory and anti-allergic effect and practically does not have mineralocorticoid activity. Various modifications of betamethasone (betamethasone dipropionate, valerate, disodium phosphate, acetate) are used as anti-inflammatory, anti-allergic drugs in the form of a variety of dosage forms: tablets, injections, suspensions, creams, ointments.

A known pharmaceutical composition having anti-inflammatory and anti-allergic effects (see RF patent No. 2225208, 2004), including the active substance - betamethasone dipropionate, water, a hydrophobic component and target additives - propylene glycol, emulsifier, poxibenzoic acid ester, antioxidant and trilon B, and as a hydrophobic component, a combination of petrolatum, paraffin wax and paraffin oil, in the following ratio of ingredients, wt.%: betamethasone dipropionate - 0.02-0.2;

hydrophobic component (combination of petrolatum, paraffin wax, paraffin oil) - 15,040,2;

antioxidant - 0.01-0.5;

propylene glycol - 2.0-15.0;

Trilon B - 0.01-0.5;

emulsifier - 3.0-15.0;

p-hydroxybenzoic acid ester - 0.02-0.5;

water - up to 100.

Sodium sulfite is preferably used as an antioxidant; high molecular weight alcohols, for example cetostearyl alcohol, can be used as an emulsifier.

Based on this technical solution, the Akrikhin Chemical and Pharmaceutical Combine OJSC created a gamut of traditionally used medicines in the form of cream for external use, Akriderm, as well as combined preparations for external use in the form of cream and ointment:

Akriderm GENTA (glucocorticosteroid + antibiotic-aminoglycoside),

Akriderm GK (glucocorticosteroid + antibiotic-aminoglycoside + antifungal agent), Akriderm SK (glucocorticosteroid + keratolytic agent).

In addition to the high therapeutic effect, prolonged administration of corticosteroids to the body can cause a number of side effects: inhibition and atrophy of the adrenal cortex, hyperglycemia, increased excretion of calcium and osteoporosis, exacerbation of peptic ulcer disease, decreased resistance to disease, obesity, etc., which is a significant disadvantage of pharmaceutical compositions and medicines based on it.

A gel for external use is known Psilo-balm of the company §! Aba ΑΓζηοίιηίΙΙοΙ AO (Germany, registration in the Russian Federation 2004), containing diphenhydramine hydrochloride as an active substance in the amount of 1 mg per 1 g of gel. Psilo-balm has an anti-allergic effect and is used in the treatment of sunburns and burns of the 1st degree, insect bites, urticaria, skin itching of various origins, itchy eczema, chickenpox, allergic skin reactions, contact dermatitis caused by contact with plants.

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An external agent Fenistil of the company фирмыοναΠίδ Sopinpsg NeaIy (Switzerland, registration in the Russian Federation 2006) containing dimetindene maleate is also known. The drug is available in the form of a gel (1 g of gel contains 1 mg of dimethindene maleate) and in the form of drops (1 ml of drops contains 1 mg of dimethindene maleate). Fenistil has an antihistamine, antiallergic and antipruritic effect. Fenistil drops are used for allergic diseases, including urticaria, year-round allergic rhinitis, hay fever, food and drug allergies, eczema and other itchy dermatoses, skin itching, insect bites. Fenistil gel is used to treat skin itching with dermatoses, urticaria, insect bites, burns (solar, household, industrial).

A disadvantage of the known tools Psilo-Balsam and Fenistil is the presence of contraindications, side effects associated with inhibition of the central nervous system, as well as the need to take precautions when using it. In addition, these gels do not have an anti-inflammatory effect, which is important for a number of domestic applications, and are also not suitable for the treatment of inflammatory eye diseases caused by allergic reactions.

The main groups of drugs used for the symptomatic treatment of allergic conjunctivitis are sympathomimetics, antihistamines, mast cell membrane stabilizers, glucocorticosteroids. All anti-allergic drugs are available in the form of drops, which limit the use of contact lenses and cause dry mucous membranes. With prolonged use, there is a risk of secondary infection, with a banal infection (drops containing antibiotics) - the risk of developing resistant strains of microorganisms. Due to the possibility of potentially dangerous unwanted effects, there are age restrictions (children and elderly patients) and restrictions on the duration of the use of drugs in these groups.

Ophthalmic drugs of the corticosteroid group have anti-inflammatory and anti-allergic effects, have a pronounced positive effect on the clinical course of inflammation of the conjunctiva of an allergic nature. At the same time, preparations of this group are characterized by an immunosuppressive effect, due to which they create favorable conditions for infection to join, and in the presence of an infectious process, for its generalization. These drugs can slow wound healing in corneal injuries, which may also be accompanied by conjunctivitis symptoms. Steroid preparations are characterized by an increase in intraocular pressure, and therefore they are contraindicated in glaucoma. Gels with anti-inflammatory and anti-allergic effects, the applicant has not been identified.

Closest to the invention is a pharmaceutical composition for treating burns (see RF patent No. 2317811, A61K 9/06, 2008), comprising the active substance No. f-hydroxyethyl) -4,6dimethyldihydropyrimedone-2 (xymedon) and a gel base. As a gel base, the composition contains a gelling agent - sodium salts of biopolymers, a water-retaining agent glycerin in an amount of at least 20 wt.%, A stabilizer, a preservative and distilled water. The specified tool has a regenerative, wound healing, improves local microcirculation activity in the treatment of burn wounds, but does not have antiallergic activity.

The problem to which the invention is directed is to create, on the basis of xymedon, a gel having anti-inflammatory and anti-allergic effects, having high therapeutic efficacy for the treatment of skin diseases, rhinitis, eye diseases.

The specified result is achieved by the pharmaceutical composition of the gel, which has anti-inflammatory and anti-allergic effects, characterized in that it includes No. ph-hydroxyethyl) -4,6-dimethyldihydropyrimedone-2 (xymedon) as the active substance, diphenhydramine, or clemastine, as the antihistamine or cetirizine and a gel base containing carbopol as a thickener, as well as polyethylene oxide with a molecular weight of 400-6000 Yes, glycerol in an amount of not more than 20%, ethyl alcohol in an amount of not more than 41% and water purified in the following ratio of components, wt.%:

xymedon - 3-10;

the specified antihistamine is 0.005-1.0;

carbopol - 0.5-1.0;

the specified polyethylene oxide is 0.5-1.0;

glycerin - 0-20.0;

ethyl alcohol - 0-41;

purified water - the rest is up to 100.

The gel may additionally contain menthol in an amount of not more than 0.5% of the total mass.

Nipagin or benzalkonium chloride is preferably used as a preservative.

The stabilizer is preferably Trilon B or Tween 80, or a mixture of Trilon B and gentamicin sulfate, or a mixture of PEO-400 and Tween 80.

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As a neutralizing agent, sodium hydroxide, or a solution of ammonia, or trometamol are used.

The proposed ratio of active and auxiliary substances is optimal, found experimentally and provides the necessary quality of the drug and its therapeutic effect.

Xymedon, by its chemical nature, is an organic base. The protonated form of xymedon (Xi H ⁺ ) or its enol form on the carbonyl in the ring does not have the necessary biological activity. Biologically active forms of xymedon were obtained in the form of xymedon hydrochloride during its synthesis.

Hydrophilic and ionic structures are formed in the aquatic environment due to lactim-lactam tautomerism, which can radically change not only the interaction of xymedon with other components of the pharmaceutical composition, but also differently affect the healing process of wounds.

The change in the hydrophilic-lipophilic ratio in the xymedon molecule occurs under the influence of the pH of the medium, the presence of other active substances or metal ions.

As an antihistamine, experimentally selected clemastine, cetirizine and diphenhydramine. Organic acids (oxalic, malic, tartaric, etc.) are formed in aqueous gels during the dissociation of antihistamines. As shown (see patent No. 2317811), succinic organic acids are not able to form esters (succinates) or stable protonated forms. Xymedon in the gel in the presence of succinic acid retains the lactam (oxo) form. As experiments have shown, when interacting with other organic acids formed during the dissociation of antihistamines, the biological activity of Xymedon is preserved. Clemastine in the form of a fumarate is fully compatible with both xymedon and other gel components. Another advantage of clemastine is that the effect is achieved at a low concentration and for a rather long time (8-12 hours).

The second group of antihistamines is cetirizine and diphenhydramine (diphenhydramine), although they are inferior in their main action to blockers of H ₁ histamine receptors, in some cases they have their advantages. So, cetirizine eliminates cold urticaria, reduces histamine-induced bronchoconstriction in mild asthma. Diphenhydramine also has a mild local anesthetic effect.

As a gel base thickener, the invention uses synthetic, rarely cross-linked polyacrylic acid polymers, whose elementary link is extremely small. Polymers of this class (carbopol I-10, carbopol 934P) have a higher permeability to the skin due to the smaller size of the globules. By virtue of the stated provisions, their aqueous solutions do not undergo microbial cantomania. For the same reasons, carbopol-based gels require significantly less preservatives and stabilizers, compared, for example, with Na-CMC and other gelling agents. The interaction of xymedon with polyacrylic acid (PAA) occurs according to a complex mechanism not only due to electrostatic, van der Waals forces and hydrophobic binding, but also due to the formation of polymer-colloidal complexes of -COOH and -COOIa units in PAA with xymedon at the nitrogen atom having a basic character. Therefore, PAA solutions with Xymedon simultaneously and quickly penetrate the skin barrier, and also form a dense surface film of PAA complexes with Xymedon, causing a prolonged action. Antihistamines easily dissociate in an aqueous solution of PAA, releasing HC1. To eliminate the pharmaceutical incompatibility caused by HC1, the main surfactants are added to the composition - PEO-400, PEG-1500, PEG-6000. In liquid polyethylene oxides, in particular in PEO-400, drugs that are difficult to dissolve in water dissolve well. The polyethylene oxides added to the composition are able to form micelles, drawing HC1 and the active substance in the main form into the center of the micelle, preventing the formation of a protonated form of xymedon. In addition, the dissociation of the active substance is suppressed by the addition of the neutralizing agent trometamol, which forms complex complexes. Therefore, in the proposed gel composition, the combination of xymedon with antihistamines while maintaining biological activity does not violate the stability of the gel.

The proposed composition may contain menthol, which has a locally irritating, analgesic, distracting, antipruritic, antiseptic, calming, coronary dilating effect. For a number of domestic applications, menthol is effective. However, for the treatment of bleeding abrasions, as well as for the treatment of inflammatory eye diseases with allergic manifestations, menthol is contraindicated.

Means used as a neutralizing agent, preservative and stabilizer are traditional in pharmacopeia practice and are used for their intended purpose. Their number is determined experimentally and depends on both the antihistamine used and the other components of the composition used.

The proposed invention allows you to prepare a gel on both an aqueous and an alcohol basis, which is also determined by the specific application.

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In the table. 1 shows the compositions of hydrophilic bases, in table. 2 - the compositions of the pharmaceutical compositions of the gels.

The pharmaceutical compositions of Examples 1-16 are prepared on both an alcohol and an aqueous basis. It is advisable to use them for sunburns and first-degree burns, insect bites, hives, itching of various origins, itchy eczema, chickenpox, allergic skin irritations (except for itching with cholestasis), contact dermatitis caused by contact with plants, in the treatment of rhinitis.

The pharmaceutical compositions of examples 17-21, it is advisable to use in ophthalmic practice, as the proposed gel stimulates the regeneration of the cornea, has anti-allergic and antipruritic effect.

A method of preparing gels is as follows.

A measured amount of carbopol is moistened with polyethylene oxide (PEO-400, PEG-1500, PEG6000). With vigorous stirring, aqueous and non-aqueous solvents are sequentially introduced in the amounts indicated in the table. 1 for each example. The hydrophilic base is brought to complete homogenization. If necessary, a neutralizing agent (sodium hydroxide, ammonia solution or trometamol), a stabilizer (Trilon B or Tween 80, or a mixture of PEO-400 and Tween 80, or a mixture of Trilon B and gentamicin sulfate) are introduced into the turbid homogeneous colloidal solution with vigorous stirring, and preservative (nipagin or benzalkonium chloride). The gel becomes clear and thick. Then, Ximedon, an antihistamine (clemastine, or cetirizine, or diphenhydramine) and, if necessary, menthol, are injected into the resulting gel. Depending on the composition, the resulting gel is adjusted with water or alcohol to 100 g.

The method of preparation of the gel is illustrated by the following examples.

Example 1. The preparation of the gel is carried out in 3 stages.

one) . 0.5 g of carbopol - I-10 is weighed, it is moistened with 6 g of a 16.7% solution of PEO400 polyethylene oxide. With vigorous stirring, 38.5 g of ethanol, 20 g of glycerol and 15 g of water are sequentially introduced. The hydrophilic base is brought to complete homogenization.

2). 5.0 g of xymedon (the gel turns yellow-orange to pink color) and 10 g of a 0.1% clemastine solution are added successively with stirring into the gel obtained. Then 5 g of a 10% alcohol solution of menthol are introduced.

3). Bring the resulting gel to 100 g with a 95% ethanol solution. The resulting gel has the following composition, wt.%:

carbopol I-10 - 0.5;

PEO-400 - 1.0;

glycerin - 20.0;

water - 30.0;

Xymedon - 5.0;

clemastine - 0.01;

menthol - 0.5;

alcohol up to 100 - the rest.

Example 2. The preparation of the gel is carried out in 4 stages.

one) . The stage is similar to example 1. Quantitative ratios, see table. 1, example 2.

2). A solution containing 0.1 g of an 18% sodium hydroxide solution, 1.7 g of a 1.6% Trilon B solution and 0.2 ml of a 2.5% solution of benzalkonium chloride is introduced into the resulting turbid homogeneous colloidal solution with vigorous stirring. The gel becomes clear and thick.

3). 5.0 g of Ximedon (gel turns from yellow-orange to pink) and 20 g of 0.1% clemastine solution are added successively with stirring into the gel obtained. Then 5 g of a 10% alcohol solution of menthol are introduced.

4) . Bring the resulting gel to 100 g with ethanol 95%.

The resulting gel has the following composition, wt.%:

carbopol I-10 - 0.5;

PEO-400 - 1.0; glycerin - 20.0; water - 30.0;

benzalkonium chloride - 0.005; sodium hydroxide - 0.018; Trilon B - 0.027;

Xymedon - 5.0;

clemastine - 0.020;

menthol - 0.5;

alcohol up to 100 - the rest.

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Example 3

one) . The first stage of preparation of the gel base is similar to example 1. Quantitative ratios, see table. 1, example 3.

2). 0.4 g of nipagin are poured into the resulting turbid homogeneous colloidal solution with stirring. Then, with vigorous stirring, 0.5 g of an 18% sodium hydroxide solution is introduced, the gel becomes transparent and thick.

3). 6.0 g of xymedon (gel turns yellow-orange to pink) and 5 g of a 0.1% clemastine solution are added successively with stirring into the gel obtained. Then 5 g of a 2% alcohol solution of menthol are introduced.

4) . Bring the resulting gel to 100 g with water.

The resulting gel has the following composition, wt.%:

carbopol i-10 - 1.0;

PEO-400 - 1.0; glycerin - 20.0; alcohol - 9.9;

nipagin - 0.4;

sodium hydroxide - 0.09;

Xymedon - 6.0; clemastine - 0.005; menthol - 0.1;

water up to 100 - the rest.

Examples 4-21. The methods for preparing the gels are similar to those described above. The quantitative ratio of the components, see table. 1 and 2 of the respective examples.

To confirm effectiveness, preclinical studies were conducted, the results of which are illustrated by the following examples.

Example 22. The results of preclinical trials of the drugs proposed according to the invention for the presence of antimicrobial and antifungal activity in experiments ίη νίίτο.

The determination of antimicrobial and antifungal activity was carried out according to the standard methodology approved by the Ministry of Health of the State Pharmacopoeia, M., Medicine, 1990, issue. 2, General analysis methods. Medicinal plant material. Guide to the study of new pharmacological substances. - M .: Medicine, 2005).

Tests were carried out in relation to: 8.aigei§ - museum (control strain) number 906, obtained from the GISK them. Tarasevich; E.co11 M-17 - museum (control strain) number B-8208 obtained from the GISK named after Tarasevich; R. aegidtokae - isolate isolated from the patient; C. a1Ysap5 - isolate isolated from the patient.

The data of the test results of ίη νίίτο of the composition of the invention according to the invention at Z. aigeyik, E. soi, Rk. 3.

As can be seen from the table, the composition of example No. 1 (for the treatment of skin diseases) has a pronounced antimicrobial effect in relation to all tested cultures. This is important in the effective treatment of various skin lesions, when during treatment there is an increase in dermatophytic infection, attachment (or amplification) of an existing secondary infection. Composition No. 17 for the treatment of ophthalmic diseases also has antimicrobial activity.

Example 23. The results of a study of the clinical effectiveness of the external use of the composition according to the invention for atopic dermatitis.

A group of patients with atopic dermatitis of 7 people was hospitalized at the NIKVI. For all patients, drugs were applied to the right half of the trunk and right limbs. On the left - traditional external products (corticosteroid ointments and creams, preparations containing antibiotics, keratolytic ointments). Atopic dermatitis in patients proceeded traditionally. For treatment, the drug was used as in Example No. 2. Five patients received the drug well, they stopped itching and the involuntary combing associated with it, the pain on touch disappeared, and a rash of rashes for 10-12 days was noted. Two other patients, due to increased itching in the foci, drug No. 2 was replaced by drug No. 16, which did not contain menthol. After changing the drug, itching decreased, sleep was restored, as the island-inflammatory phenomena decreased, and the manifestations of atopic dermatitis decreased or disappeared under the influence of external therapy, the general and emotional state of the patients was restored. The use of the compositions according to the invention in patients with atopic dermatitis gave a good clinical effect.

Next, we provide an extract from the medical history of one of the NIKVI patients.

Patient Sh.N.I., 56 years old, medical history No. 1988, was admitted to the NIKVI on December 3, 2007, with a diagnosis of atopic dermatitis. Heredity is not burdened. The disease is 51 years old (from the age of 5). During the years of the disease she received general therapy in the form of hyposensitizing and antihistamines of the 1st and 2nd generation, external therapy - corticosteroid ointments, tar preparations, etc. The process on the skin is common. Rashes in the form of foci of infiltration, erythema,

- 5 017660 grouped papular elements, onychia on the hands, in the neck, wrist joints, lower legs - pustules, purulent crusts. Diagnosis: atopic dermatitis, candidal onychia, pyoderma. The patient, along with the traditional treatment (injections of calcium gluconate, claridol, filtrum), was prescribed external therapy. The composition according to the invention (Example No. 5) was used on the skin of the right upper limb, and diprosalik on the left ointment. Observations showed a regression of clinical manifestations on the right hand after 10 days, on the left - even after 15 days, erythema and infiltration persisted.

Example 24. The results of a study of the effectiveness of the invention according to the invention for insect bites.

Patients affected by insect bites were volunteers, including adults and children from the age of 1 year (more than 100 people in total). Blood-sucking dipteran insects (mosquitoes, mosquitoes, midges, horseflies, bloodsucker flies) during bites caused pain, erythema with anemic corolla on the periphery, the appearance of blisters and itchy papules. The severity of hyperemia and edema (along with which superficial blisters with serous contents could occur) in the affected area varied very widely and depended on the age, individual sensitivity, body area and the multiplicity of bites in the victims. Immediate use of the gel made it possible to stop the pain and local edematous-inflammatory reactions, which could not be done using psilobalm or other means. In the vast majority of cases, the action of the composition, starting from the moment it was applied to the skin and lasting for 6-12 hours, did not allow all the negative phenomena that occur when these insects bite to develop. For adults, an alcohol-based gel was offered, for children - an aqueous-based gel. In the case of multiple bites, bites in the face, neck, abdomen, hips and other tender areas of the skin, the victims used the gel until the skin was completely cleansed, on average about 1-3 days.

In the case when the victim of bites, after some time (24-48 hours), blisters and vesicles formed on the skin on the erythematous-edematous background, drying out into crusts or opening with the formation of weeping erosion, the use of this composition was also effective, in comparison with drugs and remedies offered in such cases (levomycol, corticosteroid ointments). At the time of applying the gel to the affected areas and for the next 2-3 minutes, the victim experienced a slight burning sensation and chill, the pain sensation became dull, the itching and scratching associated with it stopped. Within 3-12 hours, the edema subsided, the skin acquired a normal color, the blisters localized, and the skin surface dried out. Further application of the gel (2-3 days) contributed to the rapid and complete epithelization of the erosive area of the skin.

Example 25. The results of a study of the effectiveness of the invention according to the invention on wounds, bruises, hematomas (bruises).

The gel has been successfully used as a first aid for various household injuries (bruises, abrasions, bruises). The victim E.Ya.M. at the age of 55, climbing a wooden staircase in the country, unsuccessfully slipped from it. Injury: bruised wound of the right lower leg. On the front surface of the lower leg, the skin was torn off, multiple bruises, the victim suffers from pain (the area of the bruised wound is about 60 cm ² ). After the initial treatment, a gel was applied to the wound surface and adjacent areas. According to the victim: a feeling of a slight burning sensation and cold, pain gradually disappears (within 15-20 minutes). On the first and next days there is practically no edema, the wound is dry, a crust forms on its surface, under which granulation tissue begins to form. The gel was applied 1-2 times a day. Already on the 4th-5th day, the wound practically healed without any complications with a good cosmetic result, the bruises had a pale yellow color.

Example 26. The results of a study of the effectiveness of the claimed composition in the treatment of burns (solar, thermal, chemical) Ι-ΙΙ degrees.

The composition according to the invention (alcohol-based and water-based gels, with and without menthol) was used in the treatment of burns in the spring and summer of 2007 on volunteers, including children (about 60 people in total). The number of victims included 8 people who received thermal burns of the Ι-(degree (burns with boiling water, boiling oil, steam), and 2 people who received a chemical burn. The consequences of sunburn (both thermal and chemical) were immediate discomfort, itching, burning sensation, redness and swelling of the skin, the appearance of blisters on the skin, and in some people an allergic reaction to an irritating agent.

In the acute period, when using the gel, patients noted its cooling effect, reduction of pain, itching, swelling, redness, comfort of use, restful sleep after sunbathing. The use of the gel within 3-5 hours after receiving a sunburn almost completely removed the negative components of the burn reaction.

In the case of the formation of blisters and the transition of the process into the wound phase with subsequent epithelization, the use of a gel is also effective. Xymedon, which is part of the gel, stimulates energy processes in damaged skin, has a strong regenerating effect, thereby accelerating its healing. As observations have shown, in the wound sites where the gel according to the invention was treated, good early functional and cosmetic healing results were noted.

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The average period of wound healing since receiving a sunburn was about 4 days, while treatment using, for example, levomecol took more than 7 days.

Example 27. The effectiveness of the gel in rhinitis.

The action of the proposed composition, which includes menthol, was also tested on volunteers. The gel was used in the initial period with acute rhinitis, when patients experienced mild malaise, dryness in the nasopharynx, difficulty in nasal breathing, itching in the nose and runny discharge from it, decreased sense of smell, lacrimation, and sneezing. According to patients: laying in the nasal passages of the gel for 5-20 s causes a slight burning sensation and chill, after a minute - easier breathing. The duration of the action of the gel is 10-14 hours, the gel treatment is 1-2 days (3-4 bookmarks). Inflammation of the mucous membrane stops, the discharge stops.

Example 28. The effectiveness of the claimed composition in ophthalmology.

In preclinical studies on rabbits, the antiallergic and reparative actions of gels were studied (examples 17-21).

Antiallergic and reparative activity of the eye gel No. 17 on the cornea was studied on the model of dosed erosion of the cornea. Was formed 3 groups of animals with erosion of the cornea: group I (experimental - 5 rabbits) received the inventive gel; Group II (experimental - 5 rabbits) received a comparison drug - Korneregel, 5% of the production of your company &Got; Group III (control - 5 rabbits) without treatment. Rabbits with normal clean eyes, without signs of edema and irritation were selected, the studied preparations were laid 2 times a day in both eyes of all groups of animals.

During the experiment, biomicroscopic observations of animals showed that in rabbits of the II and III experimental groups, pronounced hyperemia of the conjunctiva of the eyelids and the appearance of infiltrates on the surface of the cornea were observed for 2-3 days of treatment. The eyes of animals of the experimental group I remained calm. Epithelialization of the cornea in the group of animals receiving the application of the inventive gel occurred earlier (5.4 ± 0.3 days) compared with the group receiving Cornerogel (6.1 ± 0.3 days), and with the control group, where complete epithelization occurred only on 6.7 ± 0.3 days. The results of measurements of the erosion area in the dynamics of the use of the studied drugs showed that a 2-time use of the inventive gel per day contributes to the rapid epithelization of the eroded area of the cornea, which is not accompanied by inflammatory and allergic manifestations.

Example 29. An example of the effectiveness of the composition in case of a burn of the eyes.

The gel was successfully used to treat eye burns in 2 patients.

One of the victims received an alkali burn of the eyes and face during a chemical experiment in the laboratory. The employees who were next to the victim at that moment gave him first aid (intensive washing, neutralizing the irritating agent), and then applied gel No. 18 to the eyes and face. After 3 hours, the gel was repeated and the gel was applied the next day. face and laid in the eyes twice. The day after the injury, only slight hyperemia of the burnt face and redness of the conjunctiva were noted. A day later, the phenomena of hyperemia disappeared.

The second victim received an eye burn by welding. The next day, the victim had a burning sensation, itching, swelling, conjunctival hyperemia, and visual impairment. Apply the gel began a day later.

The antiallergic effect of the gel began to appear after 1 h: itching and burning stopped, and eye swelling decreased. Over the next day, with a 2-time gel filling in the eyes, all the negative consequences of the burn injury disappeared.

Thus, the proposed pharmaceutical composition in the form of a gel having anti-inflammatory and anti-allergic effects is an effective drug for the treatment of inflammatory and allergic skin diseases, for the treatment of vasomotor and allergic rhinitis, as well as for the treatment of inflammatory eye diseases with allergic manifestations.

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Table 1

No. gvdrof fundamentals Sample Gelling agent g Water, g Ethanol g Glycerin, g Surfactant Neutralizing agent Stabilizer Preservative one 2 3 4 5 6 7 8 nine 10 I one Sagorosh-10 0.5 fifteen 38.5 twenty PEO-400 6g 17% - - P 2 Sagoro! ϋ-10 0.5 3 38.5 twenty PEO-400 6g 17% Maon 0.1 g eighteen% Trilon B 1.7 g 1.6% Benzalkonium chloride 0.2 g 2.5% P 3 Sagororo1 and -10 1,0 51 5 twenty PEO-400 6g 17% Maon 0.5 g eighteen% Nipagin 0.4 g II 4 Sagororo1i-10 0.5 fifteen 36 twenty PEG-1500 4g 17% Maon 0.1 g eighteen% Trilon B 1.9 g 1.4% Nipagin 0.4 g P 5 Sagororo1i-10 0.5 3 33 twenty PEO-400 6g 17% Maon 0.1 g eighteen% Trilon B 1.7 g 1.6% Benzalkonium chloride 0.2 g 2.5% P 6 SayyuroSh-10 1,0 43 5 twenty PEO-400 6g 17% Maon 0.5 g eighteen% Nipagin 0.4 g P 7 Sagoro! ϋ-10 1,0 35 5 twenty PEG-6000 Zg 17% ΝηΟΗ 0.5 g eighteen% P 8 Sag οροί ϋ-10 1,0 fifty 5 twenty PEO-400 6g 17% Maon 0.1g 18% Twin 80 0.1 g Nipagin 0.4 g II nine Sagoro! ϋ-10 1,0 43 5 twenty PEG-1500 4 g 17% MaOH 2g 18% Twin 80 1.0 g Benzalkonium chloride 0.2 g 2.5% w 10 Sagoro! i-10 0.5 thirteen 41 twenty PEO-400 6g 17% Trometamol 0.5 g - Nipagin 0.4 g ΙΠ 7 Sajoro1 934 0.5 3 41 twenty PEG-1500 4 g 17% Trometamol 0.5 g Benzalkonium chloride 0.2 g 2.5% w 12 Sagoro1 and -10 1,0 fifty 5 twenty PEO-400 6g 17% Trometamol 1.0 g Nipagin 0.4 g w thirteen Sagjoro 1934 1,0 34 5 twenty PEO-400 6g 17% Trometamol 1.0 g - - w 14 Sagoro! 934 0.5 fifteen 31 twenty PEG-1500 4 g 17% Trometamol 0.5 g Nipagin 0.4 g ΠΙ fifteen Sagoro1934 1,0 42 5 twenty PEO-400 6g 17% Trometamol 1.0 g Nipagin 0.4 g w sixteen Sagoro! 934 1,0 57 8 6 PEO-400 6g 17% Trometamol 1.0 g PEO-400 7 g Twin 80 7g Nipagin 0.4 g IV 17 Sagoro! 934 0.5 60 - - PEO-400 6g 17% Maon 0.6g eighteen% Trilon B 1.0 g 3% Gentamicin Sulfate 0.6 g 4% Benzalkonium chloride 0.2 g 2.5% IV eighteen - V nineteen - - Trometamol 0.5 g V twenty - - Wah 21 - -

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table 2

No. at measure No. hydrophilic base, amount, g Antihistamine, g Ximedon g Menthol g Solvent up to 100 g Appointment one 2 3 4 5 6 7 one I 80 Clemastine 10 g 0.1% 5 5 g 10% Ethanol With burns of Ι-ΙΙ degree, insect bites, urticaria, pruritus of various origins, itchy eczema, chickenpox, allergic skin irritations (except for itching with cholestasis), contact dermatitis, rhinitis 2 P 80 Clemastine 20 g 0.1% 5 5 g 10% Ethanol 3 II 83.9 Clemastine 5 g 0.1% 6 5 g 2% Water 4 P 77.9 Cetirizine South 0.1% 7 5 g 2% Ethanol 5 II 64.5 Cetirizine 20 g 0.1% 10 e _ ol / E G 2.70 Ethanol 6 P 75.9 Cetirizine South 0.1% nine 5 g 2% Water 7 P 64.5 Cetirizine 20 g 0.1% 10 5 g 2% Water 8 P 82.5 Diphenhydramine 0.5 3 5 g 10% Water nine P 75,2 Diphenhydramine 1,0 5 5 g 2% Water 10 W 81.4 Clemastine South 0.1% 3 5 g 2% Ethanol eleven W 69.2 Clemastine 20 g 0.1% 5 5 g 10% Ethanol 12 W 83,4 Clemastine 5 g 0.1% 6 5 g 10% Water Also thirteen W 67 Clemastine 20 g 0.1% 7 5 g 10% Water 14 W 71,4 Cetirizine 15 g 0.1% 7 5 g 2% Ethanol fifteen W 75,4 Cetirizine South 0.1% nine 5 g 2% Water sixteen W 93,4 Diphenhydramine 1,0 5 - Water 17 IV 67.9 Clemastine South 0.1% 5 - Water In ophthalmic practice, it stimulates the regeneration processes of mouth-ipa, and has anti-allergic and antipruritic effects. eighteen Cetirizine 20 g 0.1% 5 - Water nineteen V 67.9 Clemastine South 0.1% 5 - Water twenty Cetirizine South 0.1% 5 - Water 21 Wah 68.1 Clemastine South 0.1% 5 - Water

Table 3

Claims (5)

CLAIM 1. A gel having anti-inflammatory and anti-allergic effects, characterized in that it includes Y- (3-hydroxyethyl) -4,6-dimethyldihydropyrimedone-2 (xymedon) as an active substance, diphenhydramine, or clemastine, or cetirizine and a gel base containing carbopol as a thickener, as well as polyethylene oxide with a molecular weight of 400-6000 Yes, glycerol in an amount of not more than 20%, ethyl alcohol in an amount of not more than 41% and purified water in the following ratio, wt.%: Ximedo 3-10 The indicated antihistamine is 0.005-1.0 Carbopol 0.5-1.0 Specified Polyethylene Oxide 0.5-1.0 Glycerol 0-20,0 Ethanol 0-41 Purified water the rest is up to 100 2. The gel according to claim 1, characterized in that it further comprises menthol in an amount of not more than 0.5% of the total mass. 3. The gel according to claim 1 or 2, characterized in that it further comprises nipagin or benzalkonium chloride as a preservative. 4. The gel according to claim 1 or 2, characterized in that it further comprises Trilon B or Tween 80 as a stabilizer, or a mixture of Trilon B and gentamicin sulfate, or a mixture of Tween 80 and PEO-400 polyethylene oxide. 5. The gel according to claim 1 or 2, characterized in that it further comprises sodium hydroxide, or an ammonia solution, or trometamol as a neutralizing agent.