Pharmaceutical composition possessing therapeutic action on various skin pathologies

FIELD: medicine.

SUBSTANCE: pharmaceutical composition possessing a therapeutic action on various skin pathologies contains triptantrin, chitosan and distilled water, a lanoline and Vaseline mixture and protein-nucleic hydrolyzate of the salmonid fishes milt in a certain mixture ratio.

EFFECT: composition enables increasing the clinical effectiveness in the skin pathologies of various origins and extending the range of pharmaceutical compositions having the therapeutic effect on the various skin pathologies.

3 tbl, 4 dwg, 7 ex

 

The invention relates to medicine and veterinary science and concerns the creation on the basis of alkaloid triptycene (koropitan) pharmaceutical compositions with a wide range of actions that can be used to treat a variety of skin disorders of humans and animals.

The problem of using universal tools external application that combines various types of pharmacological activity, constantly attracts the attention of researchers that develop new drugs. Currently, there is a growing need for integrated tools, broad-spectrum, which is determined primarily by the sharp increase in the number of inflammatory skin diseases of different etiology. These diseases are associated with heavy environmental pollution, deterioration of the functional activity of the immune system and sensitization of the population, and the formation had drug resistant strains of microorganisms, which limits the use of existing drugs because of their low efficiency.

For the treatment of skin lesions of different etiology traditionally used a wide range of medicines - antibiotics, sulfonamides, nitrofurans and other antiseptics. However, the widespread use of antibiotics has led to a rapid expiration�Yu and the spread of resistant strains.

From a huge number of medicines can be divided into several groups according to their specific action on the wound: anti-inflammatory, antimicrobial, anti-allergic, wound healing, antitumor, and other, but there are polyfunctional substances which simultaneously combine the above activity. The latter are the most promising and valuable medicines.

Tripcentral was selected as a natural antibiotic from a range of higher plants, such as Isatis tinctoria L., Polygonum tinctorium (P. tinctorium), Drouwen Candida fungi lypolitica [Y. Jahng Progress in the studies on tryptanthrin, an alkaloid of history // Arch. Pharm. Res. 2013. V. 36(5). P. 517-535], marine microorganisms Oceanibulbus indolifex [Wagner-Dobler I., et al. Oceanibulbus indolifex gen. nov., sp.nov., a North Sea alphaproteobacterium that produces bioactive metabolites // Int. J. System. Evol. Microbial. 2004. V. 54. P. 1177-1184], and has recently been found in yeast fungi of the genus Malassezia, which are part of the natural microbiome of human skin [S. Vlachos et al. Malassezia-derived indoles activate the aryl hydrocarbon receptor and inhibit Toll-like receptor-induced maturation in monocyte-derived dendritic cells // Br. Assoc. Dermatol. 2012. V. 167. P. 496-505].

Important pathobiological value triptycene as a secondary metabolite of yeast, perhaps, is that he, as natural components of the immune system of human skin, is involved in the inhibition of pathological inflammatory processes�s, for example, in pityriasis versicolor and seborrheic dermatitis [G. Gaitanis et al. The Malassezia genus in skin and systemic diseases // Clin. Microbiol. Rev. 2012. V. 25. P. 106-141; Hay R. J. Malassezia, dandruff and seborrhoeic dermatitis: an overview // Br. J. Dermatol. 2011. V. 165 (Suppl. 2). P. 2-8].

Triptastic has the qualities of a strong anti-inflammatory agent, as a specific inhibitor of cyclooxygenase COX-2 (at a dose of 1.5 μm inhibits its activity by 50%) and 5-lipoxygenase (5-LOX) enzymes whose expression increases dramatically in the period of rapid development of inflammatory processes. In low doses tripcentral inhibits the production of macrophages as NO and prostaglandin E2and has a dual inhibitory effect on Pro-inflammatory enzymes activated macrophages [Pergola S. et al. On the inhibition of 5-lipoxygenase product formation by tryptanthrin: mechanistic studies and in vivo efficacy // Brit. J. Pharm. 2012. V. 165. P. 765-776].

Known immunostimulatory composition that includes, tripcentral or its derivatives, and substances or extracts of hop cones and rosemary, including a variety of triterpenes, diterpene lactones and their conjugated derivatives [WO 2004037180, 2004.05.06].

In the patent [US 2007184133, 2007.08.09] specifies a mechanism immunostimulatory effect of such synergistic compositions related to inhibition of COX-2 and synthesis of prostaglandins, particularly prostaglandin E2.

Tripcentral can inhibit the cascade Arah�donoway acid, and NO synthesis of proinflammatory prostaglandins and leukotrienes [T. Ishihara et al. Tryptanthrin inhibits nitric oxide and prostaglandin E(2) synthesis by murine macrophages // Eur. J. Pharmacol., 2000; 407, 197-204]. Its anti-inflammatory activity tripcentral close to the modern commercial drug zileuton, which is a specific chelator of iron ions in the active center of the enzyme 5-LOX [Pergola S. et al. On the inhibition of 5-lipoxygenase product formation by tryptanthrin: mechanistic studies and in vivo efficacy // Brit. J. Pharm. 2012. V. 165. P. 765-776].

It should be noted that tripcentral has high anti-inflammatory potential in dermatological disorders, by inhibiting the activity of thymic stromal lymphopoietin and other cytokines, which play a crucial role in the development of skin inflammatory diseases [N. R. Han et al. Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP. Arch Biochem Biophys. 2014. V. 542. P. 14-20]. The complex indole compounds (indirubin, Indigo, isatin, etc.) or extracts obtained from various plants, tripcentral used in Oriental medicine for the treatment of dermatoses of various etiologies and skin lesions caused by psoriasis [Y. K. Lin et al. Indigo naturalis upregulates claudin-1 expression in human keratinocytes and psoriatic lesions. J. Ethnopharmacol. 2013. V. 145(2). P. 614-620]. Characteristically, the extract from the plant Indigo naturalis, containing as the main components triplatin, indirubin and Indigo, has a pronounced therapeutic�and properties for skin diseases, in particular psoriasis, increasing the synthesis of important functional protein skin Claudine-1 and restoring the function of tight junctions in keratinocytes [Y. K. Lin et al. Indigo naturalis upregulates claudin-1 expression in human keratinocytes and psoriatic lesions // J. Ethnopharmacol. 2013. V. 30, No. 145(2). P. 614-620].

Important is the fact that tripcentral exhibits pronounced antimicrobial activity against various types of staphylococcal (Staphylococcus aureus, S. epidermis and methicillin-resistant S. aureus strain). In its effectiveness of antimicrobial action tripcentral comparable to P-lactam antibiotics [Chiang Y. R. et al. An in vitro study of the antimicrobial effects of indigo naturalis prepared from Strobilanthes formosanus Moore // Molecules. 2013. V. 18(11). P. 14381-14396]. At doses close to 1 mg/ml, tripcentral inhibits by 50% the growth of pathogens such as B. subtilis [Schindler F., Zahner H. Metabolic products of microorganisms. 91. Tryptanthrin, a tryptophan antibiotic derived from Candida lipolytica // Arch. Microbiol. 1971. V. 79. P. 187-203] and Mycobacterium tuberculosis Mycobacterium tuberculosis [J. M. Hwang et al. Design, synthesis, and structure-activity relationship studies of tryptanthrins as antitubercular agents // J. Nat. Prod. 2013. V. 76(3). P. 354-367]. It has recently been suggested that it inhibits the growth of pathogenic microorganisms by internalrevenue in microbial DNA [Bandekar P. P. et al. Antimicrobial activity of tryptanthrins in Escherichia coli // J. Med. Chem. 2010. V. 53. P. 3558-3565].

In doses comparable to the doses of griseofulvin, tripcentral is also highly specific antifungal agent, profusecheapest against dermatophytes, especially against Trichophyton mentagraphites that cause ringworm [Honda G. et al. The antimicrobial specificity of tryptanthrin // Planta Med. 1979. V. 37. P. 172-174]. Triptastic has a high specificity of action on the pathogens of other diseases, including Helicobacter pylori - basic microbial factor responsible for the development of gastric ulcers, and protozoal infections [Scovill J. et al. // Antimicrob Agents Chemother. 2002. V. 46(3). P. 882-883].

It is also shown that tripcentral to have anticarcinogenic activity. When administered orally at a dose of 50 mg/kg, tripcentral reduces the number of cases of colon cancer in rats induced by azoxymethane [Koya-Miyata, S. et al. Prevention of azoxymethane-induced intestinal tumors by a crude ethyl acetate-extract and tryptanthrin extracted from Polygonum tinctorium Lour // Anticancer Res. 2001. V. 21. P. 3295-3300]. In addition tripcentral cupressinum colitis induced by dextran sulfate in mice, probably by inhibiting the production of interleukin-2 activated spleen cells [Micallef M. J. et al. The natural plant product tryptanthrin ameliorates dextran sodium sulfate-induced colitis in mice // Int. Immunopharmacol. 2002. V. 2. P. 565-578].

Triptastic has a strong cytotoxic activity in vitro against various tumor cell lines of human and animal [Jao C. W. et al. Isolation, Structure Elucidation, and Synthesis of Cytotoxic Tryptanthrin Analogues from Phaius mishmensis // J. Nat. Prod. 2008. V. 71. P. 1275-1279]. Interestingly, low concentrations of this alkaloid increases expression of markers of cell differen�of zerouki in human monocytic U-937) and promyelocytic (HL-60) leukemic cells, which is an indicator of differentiation into monocytes/macrophages. After the effects of high concentrations triptycene within 24 h was observed vacuolization of the cytoplasm and destruction of mitochondria. Leukemic cells are killed along the path of apoptosis within 48 h after their treatment. Action triptycene enhances Fas-induced apoptosis and increases the activity of caspase 3. These data indicate that low-dose triptycene can induce differentiation of leukemic cells, while high concentrations lead to apoptotic death [T. Kimoto et. al. Cell differentiation and apoptosis of monocytic and promyelocytic leukemia cells (U-937 and HL-60) by tryptanthrin, an active ingredient of Polygonum tinctorium Lour//Pathol. Int. 2001. V. 51. P. 315-325].

Tripcentral very effectively blocks the action and inhibits expression of various cytokines, in particular growth factor hepatocyte (HGF), which is involved in the malignant transformation of normal cells, and in the growth, invasion and metastasis of tumor cells [T. Motoki et al. Inhibition of hepatocyte growth factor induction in human dermal fibroblasts by tryptanthrin // Biol Pharm Bull. 2005. V. 28(2). P. 260-266].

Is known about the manifestation CryptoStream anti-allergic properties [JP 2006241080, 2006.09.14].

Thus, triptastic has a broad spectrum of pharmacological action, namely: anti-inflammatory, antimicrobial, anticarcinogenic, antitumor and dermis�assetnum action that allows you to create drugs that can be used successfully in skin pathologies of different etiology.

An important advantage triptycene over other natural compounds is that it is obtained by one - step synthesis oxidation of isatin [Moskovkina T. V., etc. the Synthesis of compounds of series triptycene by oxidation of isatin // Phys. body. chemistry. 2013. V. 49. P. 1760-1763].

The disadvantage triptycene is its poor bioavailability associated with low solubility in biological fluids.

In the result of solving the task of creating bioavailable compositions based triptycene we have created a gel composition having wound healing, burns, anti-inflammatory, hepatoprotective, antidiabetic and antitumor activity. Gel composition comprises triplatin, chitosan and distilled water in the following ratio of ingredients, g/l gel: tripcentral 1.5 to 2.5; chitosan 15,0-25,0; distilled water - the rest [RU 2366408 C1, 10.2009].

However, in the process of working with gel composition revealed its significant drawbacks:

1. the observed stratification of the gel form of the drug during storage creates serious difficulties for its pharmacological applied topically;

2. due to the high pharmacological� activity triptycene its concentration in the gel is unreasonably high and does not meet the optimal dose when it is applied topically for treatment of wound of skin damage;

3. decreased efficiency of the process of epithelialization and regeneration of wound damage, which is associated with two of the aforementioned disadvantages.

All these factors reduce the effectiveness of the pharmacological application of known gel compositions in various skin pathologies.

The technical result provided by the invention is to eliminate the disadvantages inherent in the known gel compositions based triptycene, and, as a consequence, the increase of efficiency of treatment of skin disorders of different etiology. The invention expands the Arsenal of pharmaceutical compositions having therapeutic effects in various skin pathologies.

The technical result is achieved in that the pharmaceutical composition having a therapeutic effect in various skin pathologies, including triplatin, chitosan and distilled water according to the invention additionally contains lanolin-vaseline mixture and nucleic acid-protein hydrolysate milk salmonids in the following ratio of components, wt.%:

Tripcentral0,005-0,015
Chitosan1,0-1,2
Lanolin-vaseline mixture 40,0-50,0
Nucleic acid-protein hydrolysate1.0 to 2.0
Distilled waterelse

The combined use of the components in the claimed composition provides a synergistic effect of the composition, which consists in the fact that each component exhibits a characteristic pharmacological properties under the action of the wound damage and pathological inflammatory processes of the skin with greater efficiency, and the concentration of start - triptycene 5-10 times lower than in the known gel compositions.

In the claimed composition tripcentral used in optimal quantitative ratio of from 0.005 to 0.015 wt.% for the existence of maximum pharmacological action. The increase in the content of triptycene (more than 0.015 wt.%) may lead to the inhibition of metabolic processes in normal cells and thus to a breakdown in the effectiveness of its action on the stage of granulation and epithelization of wound damage. The decrease in the concentration triptycene (less than 0.005 wt.%) also does not match the optimum doses of its pharmacological activity, and therefore can not achieve the desired pharmacological effect of the claimed composition.

To prepare the inventive comp�Menshevism use tripcentral, obtained by the oxidation of isatin, a commercial preparation of chitosan with 80% degree of de-acetylation and molecular weight of 100,000 Da, lanolin-vaseline mixture and nucleic acid-protein hydrolysate Molok salmon obtained by a known method [RU 2055482, 10.03.1996].

Chitosan is widely used for preparing external use of funds in the form of gels, films, sponges, colloidal solutions, as it has antibacterial, antifungal, antiviral, wound healing and immunomodulatory properties (LD50for the human body is 1.33 g/day/1 kg/weight) [Q. Li et al. Application and properties of chitosan. In: Applications of chitin and chitosan, M. F. A. Goosen, Ph.D. ed. Technomic publishing CO., Inc., Lancaster. Basel. 1997. pp. 3-29].

The selected concentration range of chitosan in the claimed composition is optimal for the existence of maximum pharmacological activity. When the concentration of chitosan of more than 1.2 wt.% is an intense formation of coating the wound in the form of a film and the violation of the outflow wound content. At a concentration of less than 1.0 wt.% chitosan has already optimal pharmacological action.

Hydrolyzed milk salmon contains such valuable biologically active products, such as deoxynucleoside, the oligonucleotides of various sizes, amino acids, dominated by arginin and lysine. These metabolites�their predecessors participate in granulation epithelialization of wound damage. It was established experimentally that the concentration of hydrolysate used in the claimed composition, optimal from the point of view of efficiency of therapeutic action and accelerate the healing process.

The method of obtaining the claimed composition includes the following stages:

1. Get the gel of chitosan known method [RU 2366408].

2. Lanolin-vaseline mixture in a weight ratio of 3:1 is melted in a water bath at 80°C and add triplatin, dissolved in chloroform, stirred and maintained at this temperature for about 20 min to evaporate the chloroform.

3. To lanolin-vaseline mixture with triptycene add the gel of chitosan in a weight ratio of 1:1 and nucleic acid-protein hydrolysate Molok salmon fish according to the recipe. The mixture is stirred until smooth and ready-ointment store at room temperature.

Selected by us experimentally the quantitative ratio of the gel and ointment (1:1) prevents their separation during storage. It is known that lanolin-vaseline ointment, especially in the first phase of wound process, does not mix with wound exudate and does not absorb wound, which impairs the possibility of cleansing the wound of pus and necrotic masses and, therefore, delays the process of regeneration of skin damag�tions [Dotsenko, B. M. . Methodical recommendations on experimental (preclinical) study of drugs for local treatment of purulent wounds (the USSR Ministry of health Pharmacological Committee). M.: 1989. 46 p.]. The authors found that the lanolin-vaseline ointment with the addition of chitosan gel in equal proportions allows to eliminate the above disadvantages, because it improves the absorption of wound exudate chitosan.

The inventive composition is a balanced, stable hydrophilic-hydrophobic ointment to ensure sufficient release of pharmacologically active triptycene to provide them with remedial action.

Improving the efficiency of use of the claimed composition for the treatment of skin pathologies of different etiology in comparison with the prototype and basic commercial drugs is proved by experiments in vivo.

All the experiments were performed on animals that had been obtained from the kennel "Pushchino" and bred in the vivarium of the Pacific Institute of Bioorganic chemistry (certificate available). Animals were maintained in accordance with international regulations, approved by order No. 267 MHSD RF from 19.06.2003, and "Guidance on experimental (preclinical) study of new pharmacological substances" (2005).

Commercial preparations for external use "Sinaflana", "Fucidin" and "plastic Surgery" was used as bazo�s drugs comparison.

Drug "Sinaflana is a of 0.025% ointment is a synthetic glucocorticoid hormone - fluocinolone acetonide anti-inflammatory, antiallergic and antipruritic effect. Used in the treatment of inflammatory and allergic skin diseases nemikrobnoy etiology. The ointment is administered to patients with eczema, neurodermatitis, pruritus, psoriasis and other chronic dry forms of inflammatory and allergic skin diseases [Mashkovsky M. D. Medicines. part 1 // M. D. Mashkovsky. - M.: Medicine, 1993. S. 675-676].

The drug is "plastic Surgery" represents a 5% methyluracyl ointment on lanolin-vaseline-based - pyrimidine derivative, is widely used for the prevention and treatment of disorders of reparative processes in the body and normalize its protective-adaptive reactions. The drug provides a local anti-inflammatory effect, normalizes metabolic processes in tissues, stimulates local phagocytosis and therefore stimulates the healing processes. The ointment does not possess direct antimicrobial activity, the suppression of vegetative in the wound secondary infection is provided indirectly through the local reactions of the immune system [Mashkovsky M. D. Medicines. part II // M. D. Mashkovsky. - M.: Medicine, 1993. P. 161-162].

The drug is "f�CIDIN" represents a 2% ointment bacteriostatic antibiotic fusidic acid. She belongs to the group of fusidin, antimicrobial compounds, the mechanism of action of which is associated with impaired protein synthesis in the bacterial cell. To fusidic acid sensitive gram-positive bacteria and gram-negative cocci [Mashkovsky M. D. Medicines. part II // M. D. Mashkovsky. - M.: Medicine, 1993. S. 306-308].

Disadvantages of each of the three aforementioned commercial remedies for the treatment of skin pathologies are the lack of universality and the narrow focus of the action.

Fig. 1 presents a comparative performance evaluation of therapeutic effect of the claimed composition, gel-based products (prototype) and other drugs comparison of erythema on the ears in an experimental model of allergic contact dermatitis (the y - axis the level of skin damage (erythema), expressed in arbitrary units; x-axis - the number of treatment applications).

Fig. 2 shows histopathological analysis of therapeutic effect of the claimed composition, gel-based products and commercial preparation Sinaflana" in the simulation allergic contact dermatitis induced by dinitrofluorobenzene (DNFB) in experimental animals.

a) negative control, no treatment; b) drug treatment "Sinaflana") treatment gel composition, g) �of Directors for the inventive composition. Sections were stained with hematoxylin-eosin; 100-fold increase.

Fig. 3 presents the effect of the claimed composition on the expression of cytokine proteins in serum, induced DNFB. (-) control - DNFB (without treatment), (+) - control - gel composition.

Designations: IL-1 - interleukin 1, IL-2 - interleukin 2, IL-4 - interleukin 4, IL-10 - interleukin 10, GM-CSF - granulocyte-macrophage colony-stimulating factor, IFN - interferon-γ, TRF - transforming growth factor-β1, TNF - tumor necrosis factor-α.

Fig. 4 shows the cytotoxic activity triptycene in vitro against various tumor cell lines: (a) murine ascitic tumor line cells of Ehrlich; (b) leukemic line human tumor cells THP-1; leukemic line human tumor cells HL-60.

The invention is illustrated by the following examples of specific performance.

Example 1. The pharmaceutical composition of composition, wt.%: triplatin - 0,005; chitosan - 1,0; lanolin-vaseline mixture - 40,0; nucleic acid-protein hydrolysate - 1,0; distilled water - the rest.

Chitosan (4 g) was dissolved with stirring in 100 ml of 3% acetic acid, add 2 volumes of 0.3 N NaOH (200 ml) and stirred. The chitosan gel was washed with distilled water to pH 5.5 to 6.0. In the resulting gel was added distilled water in volumetric rela�Oseni 1:(1-2) and homogenized using blender at 20,000 rpm for 1-3 min. Excess liquid was removed by decantation. Get white gel containing chitosan and distilled water.

Lanolin-vaseline ointment (200 grams) is melted in a water bath (80°C) and add 20 mg triptyline dissolved in 10 ml of chloroform. The mixture is stirred and maintained at 80°C for 15 min to evaporate the chloroform. Then to this mixture was added 200 ml of chitosan gel and 1.0 g of nucleic acid-protein hydrolysate Molok salmon. The mixture was stirred until a homogeneous mass and stored at room temperature.

Example 2. The pharmaceutical composition of composition, wt.%: triplatin - 0,015; chitosan - 1,2; lanolin-vaseline mixture - 50,0; nucleic acid-protein hydrolysate - 2,0; distilled water - the rest.

Made an arrangement similar way.

Physico-chemical characteristics of the pharmaceutical compositions obtained in examples 1 and 2:

consistence - soft ointment (cream);

type - hydrophobic-hydrophilic;

pH 5,5-6,0;

color - light yellow;

stability - stratification is absent;

removals - full;

shelf life: 18 months;

storage conditions - store at 4-6°C in a closed container without air.

Example 3. Pharmacological evaluation of wound healing actions of the claimed composition in relation to the burn wounds.

Experimental work was conducted on Bezmaternykh mice Lin�and CD1, causing thermal injury. Before applying thermal wounds eye scissors carefully cut some of the hair on the side between the spine and hip. Then clipped plot was further shaved with a disposable machine. Copper rod with a flat end face with a diameter of about 6 mm was heated in a boiling water bath for 5-6 h pressed butt to the shaven area of the skin of the animal. For applying next wound the cooled rod was re-heated on the water bath for 15 sec. To measure the time of contact of the rod with the skin used the stopwatch. Applying ointments started on day 2, pre-measuring the size of the wound. To determine its size to the wound applied coverslip and transferred (copied) to the contours of the wound. Glass with printed circuits would rip through the scanner in a graphic file format "BMP". The wound area was measured using Adobe Photoshop CS (version 8.0): set the on-screen grid with a side of a square 0.25 mm2and then counted the number of squares covered by the contour of the wound.

The study preparations were applied to the wound using a metal spatula in an amount sufficient to fully cover the wound. The course of treatment is 5 days. During the experiment conducted daily assessment of the condition of the wound: the formation of a scab, state�of the eschar, the presence of peripheral epithelialization, swelling and redness of the edges of the wound, the healing and the degree of recovery of the skin. Assessment of RAS was carried out individually for each animal.

In assessing the course of wound healing is of great importance objective classification as the stage of healing and the nature of the wound. In the analysis of wound healing process, we followed the classification proposed by Kuzin M. I. [Wounds and wound infection. A guide for physicians / ed Kuzin M. I., Kostyuchenok B. M. - M.: Medicine, 1990. - 592 p.], according to which this process can be divided into three phases: the inflammatory phase, which is divided into the period of vascular changes and the period of the cleansing of the wound of necrotic (dead) tissue; II phase - regeneration, formation and maturation of granulation tissue; phase III - reorganization of the scar and epithelialization.

Experimental data obtained by us on the model of burn wounds induced in laboratory mice, indicate a high therapeutic activity of the claimed composition. The effectiveness of its wound-healing actions remained higher than the rest of the investigated drugs throughout the experiment and reached the maximum 100% value on day 12 after induction of wound healing. The results are presented in table 1.

The�them, the inventive composition has a pronounced therapeutic effect on the healing process of burn wounds. It shows greater efficiency than the gel composition (prototype) and basic commercial preparations of comparison.

Example 4. Pharmacological evaluation of wound healing actions of the claimed composition in relation to the patchwork of wounds.

Experimental work was conducted on Bezmaternykh mice lines CD1, causing patchwork wounds. To obtain experimental patchwork of wounds the scalp was removed in the same way as when applying thermal wounds. Then a small anatomical tweezers delayed skin fold pinching the tweezers about 1 mm of the skin, then cut the skin directly under the ends of the tweezers with ophthalmic scissors. Applying ointments started on day 2, pre-measuring the size of the wound. Determining the size patchwork of wounds was performed as described above for burn wounds. The treatment was performed for 5 days. Assessment of RAS was carried out individually for each animal.

Experimental data obtained at the patchwork pattern of wounds induced in laboratory mice, indicate a high therapeutic activity of the proposed drug. The effectiveness of the wound healing action of the claimed composition, which on day 12 after induction of wound process�and causes 100% healing patchwork RAS, was higher than that of the gel composition and number of commercial preparations topical application. The results are presented in table 2.

Thus, the claimed composition has a strong stimulating effect on the healing process patchwork of wounds. As in the case of burn wounds, it shows greater efficiency than the gel composition and the number of well-known commercial preparations intended for external application in various skin diseases.

Example 5. The pharmacological activity of the claimed composition on the model of allergic contact dermatitis (AAA).

AKD is a skin inflammatory disease that is mediated by T-cells and is caused by repeated exposure to skin contact allergens. The pathogenesis of AAA is associated with polarization of subpopulations of cells toward T-helper 2 ways and with a corresponding change in the cytokine profile. During the development of AKD basic role of antigen-presenting cells. During stimulation of antigen the immune system is under control of numerous molecular and cellular mechanisms. There are very complex interactions of different cell types of the immune system: antigen-presenting dendritic cells or Langerhans cells, T - and b-cells, natural Kil�hernych lymphocytes keratinocytes, endothelial cells, mast cells and platelets. It should be noted that these complex interactions are under the control of numerous cytokines and chemokines [Watanabe N. et al. Contact hypersensitivity: The mechanism of immune responses and T cell balance. / J. Interferon. Cytokine Res. 2002. V. 22. P. 407-412].

Allergic skin reactions govern complex preparations containing glucocorticoids, antihistamines, mast cell stabilizers and immunosuppressants. These drugs have strong anti-allergic effect, but their prolonged use is a big problem because of the severe side effects [Martin S. F. Contact dermatitis: from pathomechanisms to immunotoxicology // Exp.Dermatol. 2012. V. 21(5). P. 382-389].

It is no coincidence that currently focus on universal connections that have high anti-inflammatory, wound healing, antimicrobial and other pharmacological activities. In a series of pharmacological experiments, we determined the effectiveness of therapeutic effect of the claimed composition in an experimental model of AAA.

5.1 Effect of the claimed composition on the skin erythema of the ears caused by dinitrofluorobenzene.

AKD ears induced DNFB, is an internationally recognized experimental model of this disease [X. Y. Yuan et al. Effects and echanisms of aloperine on 2 4-dinitrofluorobenzene-induced allergic contact dermatitis in BALB/c mice // Eur. J. Pharm. 2010. V. 629, No. 1-3, P. 147-152]. DNFB (Sigma, USA) was dissolved in a mixture (acetone:olive oil=4:1) and was used as inductor AKD. The fur was shaved in the area of the peritoneum. For active sensitization 100 µl of 0.5% DNFB was applied once to the shaved area. After five days on the inside and outside surface of the ears caused by 20 µl of 0.2% solution DNFB. Two days later, the animals re-applied the allergen in both ears for the induction of an extensive inflammatory reaction. Treatment was started the day after the last application of the allergen. As a positive control was used a gel composition and commercial preparations for topical use "Sinaflana", "Fucidin" and "Surgery". Ointments were applied to both ears once a day for 4 days. Dermatitis were scored according to the following scale: 1 - slight peeling; 2 - desquamation, infiltration, hyperemia; 3 - serous crust; 4 - ulcers.

As can be seen from the data shown in Fig. 1, the topical application of the claimed composition for 4 times leads to a much greater therapeutic effect than using gel compositions and commercial preparations of comparison.

5.2 Effect of the claimed composition on histopathological changes in the skin of the ears for dermatitis.

For the evaluation of histopathological change�tion of tissues took biopsy samples of ears size of 5 mm and were fixed in 10% solution of formaldehyde, and then embedded in paraffin and made thin sections using microtome. After that, the sections of skin were stained with hematoxylin and eosin and the resulting samples were analyzed with a microscope.

We conducted histological analysis allowed us to demonstrate that increasing the thickness of the ears induced DNFB, and infiltration of leukocytes in the epidermis and the dermis most effectively normalizes consistent treatment within 4 days of the inventive composition. This gel composition comprising tripcentral in high dose (5 to 10 times higher than in the composition of the claimed composition), and the drug "Sinaflana" containing a corticosteroid, is in its effectiveness of therapeutic action when AKD inferior to the claimed composition (Fig. 2 a-d).

5.3 the Effect of the proposed drug on the levels of cytokines in plasma of experimental animals at AAA.

Changes in the level of cytokine production (IL-1, IL-2, IL-4, IL-10, IFN-γ, GM-CSF, β-1, TNF-α, etc.) are regarded as an important pathogenic mechanism of immune dependent diseases, one of which is AAA. In the context of contemporary trends immunotherapy cytokines are markers of prognosis and course of this disease and potential therapeutic targets. A study of cytokine profile in APC enables the assessment�'it nature of inflammation, and to prescribe an appropriate anti-inflammatory therapy.

Cytokine levels were determined using enzyme-linked immunosorbent assay in samples of blood plasma. Samples of serum were taken 24 h after the last treatment. Comparative assessment of the levels of cytokine proteins was performed using sets of BD ELISA Set Mouse (BD Biosciense, USA) for interleukins IL-1, 2, 4, 10, and interferon gamma (INF-γ), tumor necrosis factor (TNF-α), transfairusa growth factor (β-1) and granulocyte macrophage-colony stimulating factor (GM-CSF) in accordance with the instructions. In each experimental group was determined by the relative content of cytokines, expressed as an average of the optical density at a wavelength of 450 nm.

As can be seen from the data shown in Fig. 3, topical application of the claimed composition leads to a severe reduction of the local secretion of the investigated cytokines, but not to the same degree. It can be seen that the inventive composition on the level of inhibition of cytokines is markedly superior to the gel composition (prototype), which indicates the effectiveness of its anti-inflammatory and normalizing action at AKD induced DNFB.

Our results indicate that the inventive composition can successfully replace many and�known commercial ointment drugs in the treatment of AAA and other inflammatory skin diseases.

Example 6. Antimicrobial activity of the claimed composition.

In the study of antimicrobial properties of the claimed composition compared its effectiveness with gel composition. Evaluation of the effectiveness of antimicrobial action produced by the formation of zones of microbial growth inhibition of the test cultures on the surface of the agar around the sample. The sample (in a volume of 100 μl) was applied directly to the agar plate, seeded with the appropriate test cultures. Records of the results of testing conducted after 24 h (claimed and gel compositions) and 48 h (inventive composition).

Data on antimicrobial activity are presented in table 3.

Analysis of the antimicrobial activity shows that all of the test cultures of microorganisms are sensitive to the claimed composition in a dose of 20 µg in 100 µl. In this case, we registered the highest activity against Staphylococcus aureus is a dangerous pathogen that causes severe purulent infection. The effect of the composition against this strain of staph is dose-dependent. At a dose of 10 μg in 100 μl claimed the drug remains active against Staphylococcus aureus, but does not show activity against other tested strains of microorganisms. It should be noted that with increasing time �expozitii from 24 to 48 h, the activity of the claimed composition increases, that may be due to the gradual diffusion triptycene of hydrophobic-hydrophilic bases.

Example 7. Determination of cytotoxic activity triptycene in vitro against various tumor cell lines.

To determine cytotoxic activity against tumor cells triptycene as the main active component of the claimed composition used the standard MTS method (an improved modification of the MTT method) [J. Barltrop et. al. // J. Bioorg. Med. Chem. Lett. 1991. V. 11. P. 611-614].

Tumor cells were seeded in 96-well plates based 60000 cells in 50 µl cell suspension for 1 hole. The plates were incubated at 37°C in atmosphere of 5% CO2within 1 days. To 50 µl existing in each well of the cell suspension was added 50 μl of a solution of the substances under study in an appropriate environment. After the incubation each well was added 20 μl MTS-reagent. Then the plates were incubated at 37°C in atmosphere of 5% CO2for the next 2 hours. Then the optical density of the medium in each well was recorded using a spectrophotometric tablet reader at 492 nm. The number of living cells (N,%) was assessed by comparison with the control by the formula:

N=(IE/IK)×100%, (3)

where IEis the intensity of the absorption medium in each pilot hole.

IK- with�ednie significance of the obtained results to the wells with 100% control.

Determination of cytotoxic activity triptycene against tumor cells in vitro was performed using ascitic Ehrlich tumor and leukemic cell lines THP-1 and HL-60. As can be seen from the data shown in Fig. 4A-C, triptastic has a pronounced dose-dependent inhibitory activity against the investigated tumor cell lines. This inhibitory concentrations triptycene causing 50% inhibition of growth of tumor cells (IC50), consists of the following values: human leukemic tumor cells HL-60 with IC50=5,8 mg/ml; murine ascitic tumor cells of Ehrlich IC50=6,68 µg/ml. the Value of IC50for human leukemic tumor cells THP-1 is about 10 μg/ml (Fig. 4a-c).

Thus, kinesology alkaloid triptastic has a high inhibitory activity against the investigated tumor cell lines. Since the concentration triptycene in the inventive compositions at least an order of magnitude higher (average of 100 μg per 1 g of the ointment base) than required for inhibition of tumor cell growth in vitro, it can be assumed that it will be effective in the treatment of skin tumors of different etiology. In this regard, the inventive composition may be recommended for her research protivoop�eve activity in vivo against a variety of malignant neoplasms of the skin.

Pharmaceutical composition having a therapeutic effect in various skin pathologies, including triplatin, chitosan and distilled water, characterized in that it additionally contains lanolin-vaseline mixture and nucleic acid-protein hydrolysate milk salmonids in the following ratio of components, wt.%:

Tripcentral0,005-0,015
Chitosan1,0-1,2
Lanolin-vaseline mixture40,0-50,0
Nucleic acid-protein hydrolysate1.0 to 2.0
Distilled waterelse



 

Same patents:

Elastase inhibitor // 2548794

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical and cosmetic industries, namely to an elastase inhibitor. The elastase inhibitor containing active ingredients presented by raspberry (Rubus idaeus L.) extract and hydroxyproline in the dry state in a certain amount, wherein the raspberry extract is prepared by using an extraction solvent specified in a group consisting as follows: water, methanol, ethanol, hydroethanol, 1,3-butylene glycol, acetone and/or ethyl acetate. The composition for external skin application containing the elastase inhibitor.

EFFECT: agent is the effective elastase inhibitor.

6 cl, 2 dwg, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, namely to production of medications for treating dermatosis. Medication according to invention, made in form of cream, contains mometasone furoate, preservative, hydrophilic no-aqueous solvent, emulsifying agent of 1st kind, emulsifying agent of 2nd kind, emollient, disodium edetate (trilon B), pH-regulating agent, and purified water in quantities, given in invention formula.

EFFECT: invention can be applied for treating inflammatory diseases and itching in case of dermatosis, yielding to glycocorticosteroid therapy.

9 cl, 3 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of organic chemistry, namely to novel derivatives of pyrazole pyridine of formula , as well as to its tautomers, geometrical isomers, enantiomers, diastereomers, racemates and pharmaceutically acceptable salts, where G1 represents H; G2 represents -CHR1R2; R1 and R2 independently on each other are selected from H; C1C6-alkoxy-C1C6-alkyl; C1-C6-alkyl; optionally substituted phenyl; optionally substituted phenyl-C1-C6-alkyl; optionally substituted morpholine-C1-C6-alkyl; or -CHR1R2 together form a ring, selected from an optionally substituted C3-C8-cycloalkyl and substituted piperidine; G3 is selected from an optionally substituted C1C6-alkoxy -C1-C6-alkyl; C1-C6-alkyl; substituted phenyl; substituted phenyl-C1C6-alkyl; G4 is selected from a substituted acyl-C1C6-alkyl, where acyl represents a group -CO-R and R stands for H or morpholine; optionally substituted C1-C6-alkyl; optionally substituted phenyl or indene; substituted phenyl-C1-C6-alkyl; optionally substituted pyridine- or furanyl-C1C6-alkyl; morpholine- or piperidine-C1-C6-alkyl; G5 represents H; where the term "substituted" stands for the groups, substituted with 1 to 5 substituents, selected from the group, which includes a "C1-C6-alkyl," "morpholine", "C1-C6-alkylphenyl", "di-C1-C6-alkylamino", "acylamino", which stands for the group NRCOR", where R represents H and R" represents a C1-C6-alkyl, "phenyl", "fluorine-substituted phenyl", "C1-C6-alkoxy", "C1-C6-alkoxycarbonyl", "halogen". The invention also relates to a pharmaceutical composition based on the formula (I) compound and particular compounds.

EFFECT: obtained are the novel derivatives of pyrasole pyridine, useful for the treatment and/or prevention of disorders or states, associated with NADPH-oxidase.

12 cl, 3 tbl, 21 ex

FIELD: medicine.

SUBSTANCE: from the 2nd-3rd day and 10 days on after admission to hospital, Derinat is administered intramuscularly as an immunomodulatory preparation for 1-2 minutes in a dose of 1.5% (75 mg) of the solution every 45 hours (as directed in the instructions). On the 3rd-4th postoperative day, at the stage of granulation formation, the wound is coated by uniform layers of an aquacomplex of glycerosolvate titanium 0.3 g per 1 square dm of the wound as local daily applications for 10-20 days.

EFFECT: higher clinical effectiveness and reduced length of treatment and side reactions accompanying the administration of immunomodulatory agents, enabled reduction of complications of the erysipelas, considerably reduced length of intoxication manifestations, accelerated regression of local manifestations, and stimulated wound regeneration.

2 ex

FIELD: medicine.

SUBSTANCE: skin care compound possessing the antifungal properties, alcoholic extract of birch leaves, pine paste, tea tree, fir, lemon and eucalyptus essences, an emulsion base in certain proportions.

EFFECT: compound possesses the pronounced antifungal properties.

4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the field of organic chemistry, namely to novel pyridine derivatives of the general formula

and to their pharmaceutically acceptable salts, where R1 stands for (C1-6) alkyloxy, CN or halogen, R2 stands for a hydrogen atom, R3 stands for a hydrogen atom or (C1-6) alkyl, R4, R5, R6, R7 are similar or different and stand for a hydrogen atom or halogen. The invention also relates to the cosmetic application of the formula (I) compound.

EFFECT: novel pyridine derivatives, useful in the treatment of diseases associated with a receptor of androgens, are obtained.

9 cl, 1 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of general formula I, their pharmaceutically acceptable salts or N-oxides. In general formula , R1 represents C1-6alkoxy, such as methoxy or hydroxy; R2 represents C3-5cycloalkyl, which is optionally substituted by one substitute specified in R4, wherein R4 means C1-4alkyl, which is optionally substituted by hydroxy, C1-4alkoxy, group -OC(O)NR5R6, wherein each of R5 and R6 independently represents a hydrogen atom, C1-4alkyl, C3-6cycloalkyl, or R5 and R6 together with a nitrogen atom where they are attached to, form pyrrolidinyl, group -NHC(O)R7, wherein R7 means C1-4alkyl, C3-5cycloalkyloxy or pyrrolidinyl, or benzyloxygroup; -C(O)NR7R8, wherein each of R7 and R8 independently represents a hydrogen atom or C1-4alkyl, which in turn can be substituted by hydroxy, oxo, cyano, group -SO2C1-4alkyl, group -SO2NR11R12, wherein each of R11 and R12 independently represents a hydrogen atom or C1-4alkyl, group -NHSO2C1-4alkyl, group -NHC(O)C1-4alkyl, group -C(O)NR7R8, wherein R7 and R8 together with a nitrogen atom, where they are attached to, form morpholinyl, -OC(O)C2-6alkenyl, phenyl, pyridinyl or C3-6cycloalkyl, or R7 and R8 together with a nitrogen atom where they are attached to, form 5-6-merous cycle specified in morpholinyl, piperidinyl, piperazinyl substituted by C1-4alkyl, or pyrrolidinyl; -COOR7, wherein R7 means a hydrogen atom or C1-4alkyl; A represents phenyl optionally one or two-substituted by cyano, halogen, hydroxyl, C1-4alkyl, halogenC1-4alkyl, C1-4alkoxy, halogenC1-4alkoxy, C1-4alkoxyC1-4alkoxy, -SO2C1-4alkyl, group -C(O)OR3, wherein R3 means a hydrogen atom or C1-4alkyl, -C(O)R3, wherein R3 means C1-4alkyl, amino, C1-4alkylamino or diC1-4alkylamino, -NR5R6, wherein R5 and R6 independently mean hydrogen, -C(O)C1-4alkyl or -SO2C1-4alkyl, -C1-4alkylNR5R6, wherein R5 and R6 independently mean hydrogen or -SO2C1-4alkyl, or -C1-4alkylC(O)OR3, wherein R3 means C1-4alkyl, -SO2NR11R12, wherein R11 and R12 independently mean a hydrogen atom or C1-4alkyl substituted by hydroxy, or R11 and R12 together with a nitrogen atom where they are attached to, form morpholinyl; pyrrolidinyl optionally substituted by cyano; pyrimidinyl; thiophenyl optionally substituted by C1-4acyl; piperidinyl; 4,5-dihydro-2H-pyridazinone substituted by C1-4alkyl; dihydrobenzofuranone; oxoindanyl; or dihydro-oxoindolyl; X and Y represent either C and N, or N and C, respectively.

EFFECT: there are prepared new compounds, which possess the inhibitory activity on PDE4.

6 cl, 53 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to using a preparation containing the strain Bifidobacterium breve and a mixture of two soluble ingredients A and B for preparing a composition for prevention and treatment of diaper skin rash in the children. The content of the carbon ingredient A in the preparation makes 5-95 wt % of total content of the ingredients A and B. The ingredients A and B differ by an average number of monosaccharide carbohydrate links with an average chain length of the ingredient A is at least 5 monosaccharide links less than the average chain length of the ingredient B, and a structure of the monosaccharide carbohydrate links.

EFFECT: invention provides reducing allergic reactions in skin rash in the children.

9 cl, 2 dwg, 7 tbl, 29 ex

FIELD: medicine.

SUBSTANCE: skin regeneration is stimulated by using a synthetic analogue of indolicidine, a natural antimicrobial peptide having formula H-Lys-Lys-Pro-Trp-Lys-Trp-Pro-Lys-Lys-Pro-Trp-Arg-Arg-NH2.

EFFECT: accelerating reparative skin regeneration following a burn injury.

2 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically to a composition for treating dermatologic diseases, preferentially skin itching. The composition causes antiallergic action and is used in treating allergic reactions (rash, urticaria), insect bites, ultraviolet erythema and skin burns. The pharmaceutical composition contains azelastine hydrochloride and benzocaine as active substances, and a hydrophobic ingredient, a hydrophilic ingredient, an emulsifying agent and a pH corrective agent as additive agents. As the pH corrective agent, the composition contains preferentially succinic acid. The pharmaceutical composition is presented as a soft dosage form, preferentially in the form of a cream.

EFFECT: composition according to the invention is characterised by high pharmacologic activity, good package extrusion, and storage-stability.

9 cl, 1 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, namely to production of medications for treating dermatosis. Medication according to invention, made in form of cream, contains mometasone furoate, preservative, hydrophilic no-aqueous solvent, emulsifying agent of 1st kind, emulsifying agent of 2nd kind, emollient, disodium edetate (trilon B), pH-regulating agent, and purified water in quantities, given in invention formula.

EFFECT: invention can be applied for treating inflammatory diseases and itching in case of dermatosis, yielding to glycocorticosteroid therapy.

9 cl, 3 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition contains drug substances and a consistency-forming base. According to the invention, it contains anaesthetics as drug substances specified in a group: anaesthesine, lidocaine, promedol and antiseptic specified in a group of: ethacridine lactate, Furacilin, dioxidine, chlorhexidine, boric acid, 0.5% silver solution in the following ratio, g in 1 ml of the mixture: anaesthetics 0.00001-0.5; antiseptics 0.00001-0.5; consistency-forming base - the rest. Besides, it contains lysozyme in an amount of 0.1-0.3 g per 1 ml of the mixture, alpha-lipoic acid as an antioxidant in an amount of 0.00001-0.5 g per 1 ml of the mixture, regenerants specified in a group of: pantothenic acid, calcium pantotenate, beta-carotene, coenzyme Q, sodium deoxyribonucleate, inosine, vitamins A, D, E, K in an amount of 0.00001-0.5 g per 1 ml of the mixture, anabolics specified in a group of: methyluracil, riboxinum, potassium orotate, orotic acid, L-carnitine in an amount of 0.00001-0.5 g per 1 ml of the mixture, glycyrrhizic acid and/or its salts in an amount of 0.00001-0.5 g per 1 ml of the mixture, recombinant interferon specified in a group of: recombinant interferon-alpha, recombinant interferon-beta, recombinant interferon-gamma in an amount of 100-1,000,000 International units, glucocorticoids specified in a group of: hydrocortisone, prenisolone, polcortolone in an amount of 0.00001-0.5 g per 1 ml of the mixture. The consistency-forming base contains the components specified in a group: hypromellose, sodium alginate, acetyl phthalyl cellulose, macrogol, polyvinylpyrrolidone.

EFFECT: improving the properties of the composition.

9 cl, 11 ex

FIELD: medicine.

SUBSTANCE: what is described is a bioactive wound coating of a hydrogel nanocomposite, which contains antimicrobial and antioxidant ingredients: silver-modified montmorillonite and fullerenol used to optimise the clinical course of the wound process, to prevent and suppress a wound infection. The wound coating can be used to treat gun-shot injuries, severe mechanical injuries, infected and uninfected wounds, including septic and persistent, granulating wounds following deep thermal, chemical and radioactive burns, in the combined therapy of trophic ulcers and bed sores at hospital, in the outpatient setting and in the field. The wound coating is elastic, not fragmented in dressing that facilitates wound care. A high sorption ability of the wound coating matrix, including of coarse-molecular ingredients of the wound effluent, provides the fast elimination of the wound bed. Using the hydrogel, i.e. possessing high degree of hydration, the wound coating meets the modern wound management in the humid medium.

EFFECT: optimum conditions for the early activation of the repair processes.

5 dwg, 2 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compositions for local application for the prevention and treatment of local eye pathologies, in particular inflammatory keratites and conjunctivitis and the dry eye syndrome, which contain as active ingredients polyunsaturated fatty acids of the omega-3 and omega-6 type, namely, EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid) and GLA (γ-linolenic acid), mixed with vitamin E acetate and combined into a stable composition in a hydrogel, that is in the disperse form in a water solution, containing one or more gel-forming polymers. The claimed compositions are especially recommended for application as artificial tears.

EFFECT: invention provides an increased efficiency of the prevention and treatment of eye pathologies.

15 cl, 15 tbl, 3 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically to a composition for treating dermatologic diseases, preferentially skin itching. The composition causes antiallergic action and is used in treating allergic reactions (rash, urticaria), insect bites, ultraviolet erythema and skin burns. The pharmaceutical composition contains azelastine hydrochloride and benzocaine as active substances, and a hydrophobic ingredient, a hydrophilic ingredient, an emulsifying agent and a pH corrective agent as additive agents. As the pH corrective agent, the composition contains preferentially succinic acid. The pharmaceutical composition is presented as a soft dosage form, preferentially in the form of a cream.

EFFECT: composition according to the invention is characterised by high pharmacologic activity, good package extrusion, and storage-stability.

9 cl, 1 tbl, 14 ex

FIELD: medicine.

SUBSTANCE: therapeutic agent contains carboxymethyl cellulose sodium salt as a base and a combination of antiseptic, 0.01% Myramistinum and metronidazole as therapeutic ingredients. The invention provides preparing the therapeutic agent possessing the antiseptic, wound-healing and sorption action on local pyoinflammatory processes in soft tissues and mucous membranes, used in surgery, dermatology, obstetrics and gynaecology, otorhinolaryngology.

EFFECT: agent possesses the higher efficacy.

2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: therapeutic agent contains an alloy of polyethylene oxide of molecular weight 400 and 1500 as a base and comprises a combination of antiseptic, benzalkonium chloride and metronidazole as therapeutic ingredients. The invention provides preparing the therapeutic agent possessing the antimicrobial, sorption and wound-healing action on local pyoinflammatory processes in soft tissues and mucous membranes, used in surgery, dermatology, obstetrics and gynaecology, otorhinolaryngology.

EFFECT: agent possesses the higher efficacy.

2 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: first, the method involves teeth cleaning, surgical site isolation with cotton swabs, drug-induced treatment of 2% chlorhexidine and drying. Then, an erosion surface and adjoining solid dental tissues are coated with a phytoapipreparation for 15-20 minutes. The preparation is presented in the form of an ointment and has the following composition, weight fractions: 40% alcoholate (1:10) of tartarian catchfly or rhizomes and roots of maral root 10 ml, 40% alcoholate (1:10) of spirea herb 5 ml, apilac 0.5 g, clove ester 0.5 ml, lanolin 25.2 g, Vaselin 58.8 g. The ointment is used once a day for 10 days with the patients advised to avoid eating for one hour.

EFFECT: method is easy-to-use and physiological, and ensures an absolute recovery.

2 ex

FIELD: medicine.

SUBSTANCE: pharmacological composition contains a therapeutic agent and a pharmaceutically acceptable base. As a therapeutic agent, it contains recombinant interferon specified in a group: recombinant interferon alpha, recombinant interferon beta, recombinant interferon gamma, as well as hypromellose, boric acid as an antiseptic, anesthesin or lidocaine as local anaesthetics in the following proportions, g per 1 ml of the mixture: recombinant interferon, IU 100-10,000,000, hypromellose 0.00001-0.5, boric acid 0.00001-0.5, anesthesin or lidocaine 0.00001-0.5, a pharmaceutically acceptable base - the rest. Besides, the pharmaceutical composition contains heparin in an amount of 0.00001-0.5 g; antibiotics specified in a group of: baneocin, levomycin, tetracycline, amoxicilline in an amount of 0.00001-0.5 g. And as a pharmaceutically acceptable base, the pharmaceutical composition contains macrogol 400, or macrogol 1500, or macrogol 4000.

EFFECT: more effective treatment.

4 cl, 9 ex

FIELD: medicine.

SUBSTANCE: ulcer region is coated with macroporous hydrogel with the concentration of lightly cross-linked acrylic polymer 0.2-0.6 wt %, gel viscosity 45-85 poises at pH from 7.0 to 7.8. The wound floor is coated with a layer 2-4mm thick, and the wound edges - 1.5-3 mm, while a periulcerous region - 1-3 mm thick.

EFFECT: healing trophic ulcer 5-15 days later and no recurrence for 1-2 years as shown by patient's follow-up.

3 ex

FIELD: food industry.

SUBSTANCE: biologically active food additive strengthening the organism adaptive power and body defences and having anti-inflammatory and antioxidant activity contains vegetal origin components represented by a complex extract of devil's-club root, Rhaponticum carthamoides root, Hedysarum neglectum Ledeb root, celery roots and leaves, rhodiola rosea root, Japanese angelica tree roots, boschniakia rossica roots, Hungarian sainfoin herb, magnolia-vine fruits; additionally the additive contains chitosan, trepang fermentative hydrolysate, ascorbic acid, taurine, glutathione, nicotinamide, vitamin B1, vitamin B2, vitamin B6, vitamin B12, folic acid, anhydrous calcium chloride, magnesium chloride, zinc chloride, bee honey at preset ingredients ratio.

EFFECT: biologically active food additive promotes effective strengthening of the organism adaptive power and body defences and human aging retardation.

4 tbl, 6 ex

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