RU2535052C1 - Pharmaceutical composition containing lysine, proline and triterpenic acid derivatives for treating and preventing viral infections caused by rna- and dna-containing viruses, such as: influenza, herpes, herpes zoster, human papilloma, adenoviruses, as well as bacterial infections caused by gram-positive and gram-negative microorganisms - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: pharmaceutical composition possessing antiviral and antibacterial activity and containing L-N-2,6-diamino-hexanoyl-D-glucosamine, L-y-glutamyl-cysteinyl-glycyl-proline, lysine glycyrisinate, desoxyribonuclease, palmitoyl hydroxypropyl trimmonium amylopectin/glycerin cross polymer, hydroxypropyl-beta-cyclodextrin, D,L-pyrrolidone carboxylate N-cocoyl ethylarginate, escin, an emulsifying agent, a preserving agent, a pH control agent, demineralised water in certain amounts. The pharmaceutical composition possessing antiviral and antibacterial activity and containing L-N-2,6-diamino-hexanoyl-ascorbyl phosphate, N-pyrrolidine-carbamoyl-D-glucosamine, lysine ursolate, ribonuclease, a modified acrylic thickening agent, hydroxypropyl-beta-cyclodextrin, D,L-pyrrolidone carboxylate N-cocoyl ethylarginate, glycyrrhizic acid, an emulsifying agent, a preserving agent, a pH control agent, demineralised water in certain amounts. The pharmaceutical composition possessing antiviral and antibacterial activity and containing L-N-2,6-diamino-hexanoyl-hinokitiol, N-pyrrolidine-carbamoyl-D-glucosamine, lysine betulinate, collagenase, palmitoyl hydroxypropyl trimmonium amylopectin/glycerin cross polymer, hydroxypropyl-beta-cyclodextrin, chlorhexidine bigluconate, D-panthenol, an emulsifying agent, a preserving agent, a pH control agent, demineralised water in certain amounts. The pharmaceutical composition possessing antiviral and antibacterial activity and containing fusidoyl lysine, lysyl-valyl-proline pomolate, proline escinate, lysozyme, hydroxypropyl trimmunium maltodextrin, cross polymer, hydroxypropyl-beta-cyclodextrin, D,L-pyrrolidone carboxylate N-cocoyl ethylarginate, cedar extract, an emulsifying agent, a preserving agent, a pH control agent, demineralised water in certain amounts.

EFFECT: compositions possess expressed antiviral and antibacterial activity and are stable.

4 cl, 2 tbl, 11 ex

Description

The present invention relates to medicine, namely to a pharmaceutical composition containing derivatives of lysine, proline and triterpene acid, which can be used in medicine for the treatment and prevention of viral infections caused by RNA and DNA-containing viruses, such as influenza, herpes, herpes zoster lichen, human papilloma, adenonoviruses, as well as bacterial infections caused by gram-positive and gram-negative microorganisms.

There are known topical drugs used for the treatment and prevention of herpes virus infections, containing antiviral components that are not enzymes, for example Zovirax ™ cream (acyclovir); Epigen intim ™ spray (glycyrrhizic acid); ointments: alpizarin, helepin, flacoside containing plant extracts.

Known proline (pyrrolidine-α-carboxylic acid) is a heterocyclic amino acid (more specifically, an amino acid). It exists in two optically isomeric forms - L and D, as well as in the form of a racemate. L-Proline is one of twenty proteinogenic amino acids. It is believed that proline is part of all the proteins of all organisms. Especially rich in proline is the main protein of connective tissue - collagen. Proline contains a nitrogen atom connected to the previous amino acid residue, amino acid radical and the CH group. It bends the peptide chain very sharply. In the composition of collagen, proline with the participation of ascorbic acid is oxidized to hydroxyproline. Alternating proline and hydroxyproline residues contribute to the creation of a stable three-helix collagen structure that gives the molecule strength (http://ru.wikipedia.org/wiki/%CF%F0%EE%EB%E8%ED).

From RU 2010151556 a composition is known having an antiviral and antibacterial effect, containing lysozyme, escin, liposomes. The difference between the claimed invention from RU 2010151556 is that the composition also contains derivatives of lysine, proline, triterpene acids.

From RU 2379312, a pharmaceutical composition is known containing lysine-based compounds used in the treatment and prevention of HIV infection.

Known food supplement "Lysit" based on lysine, which has an immunostimulating effect and is used in the prevention and complex treatment of chronic viral infections, especially with urogenital viral infections and herpes (Herpes simplex and Herpes zoster) (http://www.apollux.com/product -01.htm).

Known lysine (2,6-diaminohexanoic acid) is an aliphatic amino acid with pronounced base properties. Lysine is an indispensable amino acid that is part of almost any protein, it is necessary for growth, tissue repair, production of antibodies, hormones, enzymes, and albumin. This amino acid has an antiviral effect, especially against viruses that cause herpes and acute respiratory infections (Found from the Internet: http://ru.wikipedia.org/wiki/%CB%E8%E7%E8%ED).

Known L-lysine escinate, which reduces the activity of lysosomal hydrolases, which prevents the splitting of mucopolysaccharides in the walls of the capillaries and in the connective tissue that surrounds them and thus normalizes the increased vascular-tissue permeability and has an antiexudative (decongestant) and analgesic effect (http: // www .vidal.ru / poisk_preparatov / l-lysine-aescinat.htm).

The known drug Infezol 40 in the form of an infusion solution containing lysine and used to stimulate the anabolic processes of parenteral nutrition (http://www.vidal.ru/poisk_preparatov/infesol-40.htm).

Usnic acid and its oxidized derivative are known from RU 2464033, which can be used as inhibitors of the reproduction of influenza virus.

Known betulinic acid (3β-hydroxy-20 (29) -lupaen-28-oic acid) is a natural pentacyclic triterpenoid. It is contained in the bark of some plant species, mainly fluffy birch (Betula pubescens), from which it got its name. Betulinic acid and its derivatives have anti-inflammatory, antitumor and anti-HIV activity (Pisha E. Method for selectivity inhibiting melanoma, using betulinic acid. Nat. Med. 1995. Vol. 1. P. 1046-1051 Fujioka T. Compounds and methods of use to treat HIV infections. J. Nat. Prod. 1994. Vol. 57. P. 243-247.).

Ursolic acid is known - a pentacyclic triterpene compound, isolated from plant materials, exhibits physiological activity both with external and internal use. Its anti-inflammatory, antitumor and antimicrobial properties allow its use in cosmetics. Ursolic acid and its isomer, concomitant with it in most plants, oleanolic acid, have been recommended for the treatment and prevention of skin cancer in several countries. Both triterpene compounds promote hair growth by stimulating peripheral blood flow in the scalp and activating maternal hair cells. Treating the skin with drugs that include these compounds prevents hair loss and dandruff. For ursolic acid and its derivatives, a wide spectrum of biological activity has been identified: anti-inflammatory, hypocholesterolemic, anti-atherosclerotic, antimicrobial, hypolipidemic, pacemaking. In addition, ursolic acid can be used as a protein synthesis modifier, as a cosmetic, as a means against lymphocytic leukemia and an antitumor drug (http://www.nioch.nsc.ru/russ/research/res_6.htm).

Data on the antiviral activity of grinding acid are known. (http://www.ijpbs.net/vol-2_issue-3/pharma_science/44.pdf).

Derivatives of betulinic acid used to treat viral infections, in particular HIV infection, are known from WO 2012106188, US 2011313191, US 2012101098.

From KR 20110018671, pharmaceutical compositions are known containing triterpenic acids for the prophylaxis and treatment of cardiovascular disorders caused by hypercholesterolemia.

FROM KR 2010040107 known compositions containing triterpene acid to eliminate wrinkles.

From JP 2011020989, a method for stabilizing triterpenic acid by N-methypyrrolidone is known.

Derivatives of betulinic acid known as antitumor agents are known from RU 2445317.

From WO 2011051520, compositions containing triterpenic acids as an auxiliary component in protein vaccines are known.

An ointment containing a corticosteroid and beta-cyclodextrin with anti-inflammatory and anti-allergic effects is known from RU 2098135, in which the use of beta-cyclodextrin provides an increase in the bioavailability of the drug, prolongation of the action, halving the amount of the active substance and reducing side effects, as well as cheaper product.

From RU 2188004 C2 (WELFIDE CORPORATION), 08/27/2002, it is known to use hydrogenated lecithin in a pharmaceutical composition for the treatment of hydrogenated lecithin, egg protein and soya lecithin (p. 4, last paragraph).

From RU 2302857 C2 (TROMSDORF GMBH UND CO. KG ARTSNAYMITTEL) (description, p. 8 and 9), purified water is known as a patch adhesive and monomers or mixtures thereof such as methyl methacrylate and butyl methacrylate are suitable adhesives.

Known medical wipes containing deoxyribonuclease and liposomes from moisture-resistant paper and non-woven material "Spanbond" for the prevention of herpes (RU 2008140954).

From RU 2006114277, a cosmetic composition is known comprising deoxyribonuclease and / or ribonuclease for the prevention of herpes virus infection.

There are known topical medicines and cosmetics used for the treatment and prevention of scars, ulcers and wounds containing enzymes, for example, Iruksol ™ ointment containing the enzyme: clostridiopeptidase A and the antibiotic chloramphenicol (http://www.rlsnet.ru/tn_index_id_1605. htm); Karipazim ™ powder containing enzymes: papain and lysozyme, for the prevention of scars (http://www.caripazymum.ru/instruction.html); Fermencol gel containing a complex of collagenolytic proteases (http://fermencol.ru/); Moricrol balm containing the enzyme: moricrazu (http://ekogoods.ru/catalog/11-balzam_%ABmorikrol%BB), Sodermix cream containing the enzyme: superroxiddismutase (http://sodermix.ru/).

Known drugs that do not contain enzymes, but are used to treat and prevent ulcers and wounds, for example Kontratubeks gel, including heparin, onion extract and allantoin (http://contractubex.ru/about/active_ingredients/), Kelofibraz cream containing a combination of heparin , camphor and urea (http://apteka-evrofarm.com/kelofibraze_kelofibrase_krem_50_g_review_6/), Zeraderm silicone coating consisting of polysiloxane, zinc oxide, vitamins E and K, coenzyme Q (http://zeraderm.su/), silicone gels Scan-fade, Kelo-Cote, Dermatix (http://www.dermatix-gel.ru/pages/informaciya_dlya_specialistov.html; http://www.kelo-cote.ru/kelo/harakteristiki_kelo-cote.php; http: //www.scarfade .com /), Camelox oil with vitamin E, wheat germ oil and rosemary essential oil (http://vertex.spb.ru/catalog/37/19/kameloks_maslo_s_witaminom_e_i_rozmarinom.html).

Known combination drug Hexalysis, containing as antimicrobial components - biclotimol and lysozyme, enoxolone isolated from glycyrrhizic acid as an anti-inflammatory component (http://www.vidal.ru/poisk_preparatov/hexalyse~22640.htm).

Known drug "Sanguirythrin", produced in the form of tablets, solution and liniment, used for purulent-inflammatory diseases (http://medi.ru/doc/g3418.htm).

Known drugs "Collagenase KK" and "Collalysin" for enzymatic cleansing of wounds of various etiologies, trophic ulcers, accelerated rejection of necrotic tissue and scab after burns and frostbite, with cicatricial changes in the skin of the eyelids and conjunctiva, simblefarone (http://www.rlsnet.ru /tn_index_id_5958.htm; www.rlsnet.ru/tn_index_id_5958.htm).

There are known topical cosmetics used for the prevention of herpes containing antiviral components that are not enzymes, for example, extracts of medicinal plants and germanium-organic compounds (Antiherpetic prophylactic lipstick '' Antigerpes '' (P16 9158 915854 71.100.70) 292472. TU 9124-001 -00358210-96), glycyrrhizic acid ointment "Herpinat" ointment; ban. 20 ml; No. 77.01.12.915.P.02970.02.00 from the Research Institute of Atherosclerosis of the Russian Academy of Natural Sciences (Russia), INAT-PHARMA (Russia) (http://www.biomedservice.ru/publish/pub16.htm).

A cosmetic enzyme-containing composition is known, wherein the enzyme is selected from the group of proteinases, including trypsin, chymotrypsin, bromelain, papain and ficin, as well as lysozyme, elastase, α-lipase and α-amylase, which is used to treat acne, skin care and skin cleansing (DE 4305460). The described composition does not contain nuclease enzymes with direct antiviral activity, and therefore cannot be used to prevent viral infections.

A toothpaste with an enzyme-containing composition is known, where the enzyme is selected from the group of proteinases including papain (Rembrandt Whitening Toothpaste (USA), as well as a paste containing lysozyme, glucose oxidase, lactoperoxidase and lactoferrin (Biotene toothpaste) (Finland) which is used to treat xerostomia.

Known drug "Lysozyme", produced in the form of hermetically sealed vials of 0.05; 0.1 and 0.15 g, which has a bacteriolytic effect and has the ability to stimulate the nonspecific reactivity of the body.

Known pharmaceutical preparation "Deoxyribonuclease", produced in the form of lyophilized powder in hermetically sealed vials and ampoules of 0.005; 0.01; 0.025 and 0.05 g. This drug is prescribed for herpetic keratitis, adenoviral conjunctivitis, to reduce viscosity and improve the evacuation of sputum and pus in bronchiectasis and is used topically in the form of a 0.2% solution in isotonic sodium chloride solution.

Known pharmaceutical preparation "Ribonuclease", produced in the form of lyophilized powder in hermetically sealed vials of 0.01 g. This drug is prescribed for diseases of the respiratory tract with difficult to separate sputum, periodontosis, gingivitis, purulent wounds, trophic ulcers, tick-borne encephalitis, thrombophlebitis sprinkled wound surface in the amount of 0.025-0.05 g.

Pharmaceutical compositions containing derivatives of lysine, proline and triterpenic acid, which can be used in medicine for the treatment and prevention of viral infections caused by RNA and DNA-containing viruses, such as influenza, herpes, shingles, human papilloma, adenonoviruses, and bacterial infections caused by gram-positive and gram-negative microorganisms are not described.

Thus, the object of the present invention is to provide a pharmaceutical composition containing derivatives of lysine, proline and triterpene acid, which can be used in medicine for the treatment and prevention of viral infections caused by RNA and DNA-containing viruses, such as: influenza, herpes, herpes zoster, human papilloma, adenonoviruses, as well as bacterial infections caused by gram-positive and gram-negative microorganisms.

The present invention provides a pharmaceutical composition comprising, as an active ingredient, 0.001-5.00 wt.% Derivatives of lysine, 0.001-5.00 wt.% Proline and 0.001-5.00 wt.% Triterpene acid, as a carrier, 0, 01-20.0 wt.% Liposomes or β-cyclodextrins, including hydroxypropyl-β-cyclodextrins, or silicone quaternium-16, or guarhydroxypropyltrimmonium chloride, or polyquaternium, or palmitoylhydroxypropyltrimmonium amylopectin / glycerin, crosspolymer, or xanthan gum, hydroxymethyl, or acrylated, or 7-9700; 7-9800; 7-9850; 7-9900), or DC silicone fluid Q7-9120 (Q-9180), or DC Silmogen carrier, or DC ST-Elastomer 10, or other silicones PDMS structures or fullerenes and pharmaceutical and acceptable polymeric carriers or excipients.

As a preferred embodiment of the claimed invention, there is provided a pharmaceutical composition as defined above, further comprising one or more anti-inflammatory ingredients.

Most preferred is a pharmaceutical composition for the treatment and prophylaxis of viral and bacterial infections, containing as active ingredient 0.001-5.00 wt.% Lysine derivatives: lysine ascorbyl phosphate, LN-2,6-diamino-hexanoyl ascorbyl phosphate, LN-2,6 -diamino-hexanoyl-D-panthenol, LN-2,6-diamino-hexanoyl-sphagnol, LN-2,6-diamino-hexanoyl-isothimol, fusidoylylisine, LN-2,6-diamino-hexanoyl-hinokithiol, usnin lysine, LN-2,6-diamino-hexanoyl-usnic acid, LN-2,6-diamino-hexanoyl-D-glucosamine, lysine ursolate, glycyl-lysyl-proline and glycyrrhizinate, lysyl-glycyl-proline is milled, ursoloylisine, oleanoyllysine, betulininolysine, pomolyllisine, Ly-glutamyl-cysteinyl-glycyl-lysine, 0.001-5.00 wt.% proline: ascorbyl phosphate proline, N-pyrrolidine-carbo-amine-carbo amine , proline oleanolate, proline usninate, glycyl-methionyl-proline glycyrrhizinate, lysyl-valyl-proline grinding, ursoloylproline, oleanoylproline, betulinoylproline, milled proline, Ly-glutamyl-cysteinyl-glycyl-proline and 0.001-5.00%. proline escinate, lysine glycyrrhizinate, lysine milling, lysine betulinate, lysine on ursolate, lysine oleanolate, as a carrier - 0.01-20.0 wt.% liposomes or β-cyclodextrins, incl. hydroxypropyl-β-cyclodextrin, or silicone quaternium-16, or guarhydroxypropyltrimmonium chloride, or polyquaternium, or palmitoylhydroxypropyltrimmonium amylopectin / glycerin, crosspolymer, or xanthan gum, hydroxymethyl, or hydroxymeridone, or sodium hydroxide 7-9700; 7-9800; 7-9850; 7-9900), or DC silicone fluid Q7-9120 (Q-9180), or DC Silmogen carrier, or DC ST-Elastomer 10, or other silicones PDMS structures, or fullerenes and pharmaceutical . Polymer acceptable carriers or excipients, the following component ratio, wt%:

L-N-2,6-diamino-hexanoyl-D-glucosamine 0.001-5.00 L-y-glutamyl-cysteinyl-glycyl-proline 0.001-5.00 Lysine glycyrrhizinate 0.001-5.00 Deoxyribonuclease 0.001-5.00 Silicone Quaternium-16 or guarhydroxypropyltrimmonium chloride or polyquaternium or palmitoylhydroxypropyltrimmonium amylopectin / glycerin crosspolymer or xanthan gum or carrageenate or modified acrylic thickener or hydroxypropyltrimmonium maltodextrin cross-polymer or silicone-based adhesives (DC 7-9700; 7-9800; 7-9850; 7-9900) or DC silicone fluid Q7-9120 (Q-9180) or DC silmogen carrier
or DC ST-Elastomer 10 or other silicones PDMS structures 0.05-5.00 Hydroxypropyl Beta Cyclodextrin 0.10-5.00 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01-5.00 Escin 0.01-5.00 Emulsifier 0.01-5.00 Preservative 0.01-1.00 PH regulator 0.01-1.00 Demineralized water Rest

As another preferred embodiment of the claimed invention, a pharmaceutical composition is provided in the following ratio of components, wt.%:

L-N-2,6-diamino-hexanoyl ascorbyl phosphate 0.001-5.00 N-pyrrolidine-carbomoyl-D-glucosamine 0.001-5.00 Lysine ursolate 0.001-5.00 Ribonuclease 0.001-5.00 Silicone Quaternium-16 or guarhydroxypropyltrimmonium chloride or polyquaternium or palmitoylhydroxypropyltrimmonium amylopectin / glycerin crosspolymer or xanthan gum or carrageenate or modified acrylic thickener or hydroxypropyltrimmonium maltodextrin cross-polymer or silicone-based adhesives (DC 7-9700; 7-9800; 7-9850; 7-9900) or DC silicone fluid Q7-9120 (Q-9180) or DC Silmogen carrier or DC ST-Elastomer 10 or other silicones PDMS structures 0.05-5.00

Hydroxypropyl Beta Cyclodextrin 0.10-5.00 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01-5.00 Glycyrrhizic acid 0.01-5.00 Emulsifier 0.01-5.00 Preservative 0.01-1.00 PH regulator 0.01-1.00 Demineralized water Rest

As another preferred embodiment of the claimed invention, a pharmaceutical composition is provided in the following ratio of components, wt.%:

L-N-2,6-diamino-hexanoyl-quinokithiol 0.001-5.00 N-pyrrolidine-carbomoyl-D-glucosamine 0.001-5.00 Lysine betulinate 0.001-5.00 Collagenase 0.001-5.00 Silicone Quaternium-16 or guarhydroxypropyltrimmonium chloride or polyquaternium or palmitoylhydroxypropyltrimmonium amylopectin / glycerin crosspolymer or xanthan gum or carrageenate or modified acrylic thickener or hydroxypropyltrimmonium maltodextrin cross-polymer or silicone-based adhesives (DC 7-9700; 7-9800; 7-9850; 7-9900) or DC silicone fluid Q7-9120 (Q-9180) or DC Silmogen carrier or DC ST-Elastomer 10 or other PDMS silicones the structure 0.05-5.00 Hydroxypropyl Beta Cyclodextrin 0.10-5.00 Chlorhexidine bigluconate 0.01-5.00 D-panthenol 0.01-5.00 Emulsifier 0.01-5.00 Preservative 0.01-1.00 PH regulator 0.01-1.00

Demineralized water Rest

As another preferred embodiment of the claimed invention, a pharmaceutical composition is provided in the following ratio of components, wt.%:

Fusidoyllisine 0.001-5.00 N-pyrrolidine-carbomoyl-D-glucosamine 0.001-5.00 Proline escinate 0.001-5.00 Lysozyme 0.001-5.00 Silicone Quaternium-16 or guarhydroxypropyltrimmonium chloride or polyquaternium or palmitoylhydroxypropyltrimmonium amylopectin / glycerin crosspolymer or xanthan gum or carrageenate or modified acrylic thickener or hydroxypropyltrimmonium maltodextrin crosspolymer 0.05-5.00 Hydroxypropyl Beta Cyclodextrin 0.10-5.00 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01-5.00 Thuja extract 0.01-5.00 Emulsifier 0.01-5.00 Preservative 0.01-1.00 PH regulator 0.01-1.00 Demineralized water Rest

The active ingredients of the claimed pharmaceutical composition are: lysine derivatives: lysine ascorbyl phosphate, LN-2,6-diamino-hexanoyl-ascorbyl phosphate, LN-2,6-diamino-hexanoyl-D-panthenol, LN-2,6-diamino-hexanoyl-sphagnol , LN-2,6-diamino-hexanoyl-isotimol, fusidoyllysine, LN-2,6-diamino-hexanoyl-quinokithiol, lysine usninat, LN-2,6-diamino-hexanoyl usninovoy acid, LN-2,6-diamino -hexanoyl-D-glucosamine, ursolate lysine, glycyl-lysyl-proline glycyrrhizinate, lysyl-glycyl-proline molybdenum, ursoloyl lysine, oleanoyl lysine, betulinino lysine, molyllysine Ly-glutamyl-cysteinyl-glycyl-lysine, proline derivatives: proline ascorbyl phosphate, N-pyrrolidine-carbomoyl-D-glucosamine, proline oleanolate, proline usnin, glycyl methionyl proline glycirrzinate, lysyl-valyl proline pomolanolin, ursolo betulinoylproline, milled proline, Ly-glutamyl-cysteinyl-glycyl-proline, derivatives of triterpenic acid: proline aescinate, lysine glycyrrhizinate, lysine molyate, lysine betulinate, lysine ursolate, lysine oleanolate, enzymes: deoxyribonuclease, rhizolucinase, yi, D-panthenol, glycyrrhizic acid, chlorhexidine, D, L-pyrrolidone carboxylate N-cocoyl etilarginata and escin. LN-2,6-diamino-hexanoyl-sphagnol, LN-2,6-diamino-hexanoyl-isothimol, fusidoyllysine, LN-2,6-diamino-hexanoyl-quinokithiol, usninate lysine, LN-2,6-diamino-hexanoyl -usnic acid, ursolate of lysine, glycyl-lysyl-proline glycyrrhizinate, lysyl-glycyl-proline molymene, ursolooyl lysine, oleanoyl lysine, betulininoyl lysine, pomolyl lysine, proline oleanolate, usninate proline, glycyl-methionyl-proline lolinolysis , oleanoylproline, betulinoylproline, milled proline, lysine glycyrrhizinate, lysine milling, lysine betulinate, l izina ursolate, lysine oleanolate, which have a pronounced antiviral effect in viral infections caused by RNA and DNA-containing viruses, such as influenza, herpes, herpes zoster, human papilloma, adenonoviruses and others, antimicrobial effect against bacterial infections caused by gram-positive and gram-negative microorganisms. Lysine ascorbyl phosphate and L-N-2,6-diamino-hexanoyl ascorbyl phosphate contribute to the synthesis of collagen due to the complex effect: increasing the concentration of the substrate source for collagen synthesis (lysine) and stimulating the formation of hydroxy lysine. L-N-2,6-diamino-hexanoyl-D-panthenol and L-y-glutamyl-cysteinyl-glycyl-lysine accelerate tissue regeneration. L-N-2,6-diamino-hexanoyl-D-glucosamine and N-pyrrolidine-carbomoyl-D-glucosamine positively affect the synthesis of connective tissue. Lysozyme catalyzes the hydrolysis of 1,4-bonds between N-acetylmuramic acid and 2-acetamido-2-deoxy-D-glucose (N-acetylglucosamine) contained in mucopolysaccharides, mucopeptides and chitin of the cell walls of bacteria, fungi and protozoa, it has a bright pronounced antimicrobial: destroys the cell walls of most gram-positive and some gram-negative bacteria, mycostatic: delays the development of microscopic fungi, as well as wound healing effect. Lysine, an antagonist of arginine, inhibits the synthesis of viral proteins. Glycyrrhizic acid and its salts are used as an antiviral agent for external and local use. Glycyrrhizic acid is active against DNA and RNA-containing viruses, including various strains of Herpes simplex, Varicella zoster viruses, human papilloma viruses, cytomegaloviruses. The antiviral effect is apparently associated with the induction of the formation of interferon. Interrupts the replication of viruses in the early stages, causes the virion to exit the capsid, thereby preventing its penetration into the cells. This is due to selective dose-dependent inhibition of phosphorylating kinase P. It interacts with the structures of the virus, changing various phases of the viral cycle, which is accompanied by irreversible inactivation of viral particles (which are in a free state outside the cells), blocking the introduction of active viral particles through the cell membrane into the cell, as well as impaired ability viruses to the synthesis of new structural components. Inhibits viruses in concentrations that are non-toxic to normally functioning cells. Virus strains resistant to acyclovir and iodouridine are highly sensitive to glycyrrhizic acid. It also has anti-inflammatory, analgesic and tissue regeneration-enhancing effects both in early manifestations of viral infection and in ulcerative forms (http://www.vidal.ru/poisk_preparatov/act_1347.htm).

D-glucosamine is an agent that affects the exchange in cartilage. Replenishes the natural deficiency of glucosamine, stimulates the synthesis of proteoglycans and hyaluronic acid of the synovial fluid, increases the permeability of the joint capsule, restores the enzymatic processes in the cells of the synovial membrane and articular cartilage. It promotes the fixation of sulfur during the synthesis of chondroitin sulfuric acid, facilitates the normal deposition of calcium in bone tissue, inhibits the development of degenerative processes in the joints, restores their function and reduces pain (http://www.vidal.ru/poisk_preparatov/act_473.htm).

Fusidic acid is an antibiotic that has a bacteriostatic or bactericidal effect. The mechanism of action is associated with the suppression of protein synthesis due to inhibition of the factor necessary for translocation of protein subunits and the elongation of the peptide chain, which subsequently leads to the death of the pathogen. Highly active against Staphylococcus spp., Especially Staphylococcus aureus and Staphylococcus epidermidis (including methicillin-resistant strains), Nocardia asteroides, Clostridium spp. Less active against Streptococcus spp., Enterococcus spp., Neisseria spp., Bacteroides spp., Mycobacterium tuberculosis, Mycobacterium leprae. Fusidic acid is active against some protozoa, including Giardia lamblia, Plasmodium falciparum (http://www.vidal.ru/poisk_preparatov/act_1197.htm).

Ascorbyl phosphate is a stable form of vitamin C that stimulates the formation of collagen in the skin, while providing antioxidant protection.

Chlorhexidine is an antiseptic and disinfectant. Depending on the concentration used, it exhibits both bacteriostatic and bactericidal action. The bacteriological effect of both aqueous and alcohol working solutions is manifested in a concentration of 0.01% or less; bactericidal - in a concentration of more than 0.01% at a temperature of 22 ° C and exposure for 1 min. Fungicidal action - at a concentration of 0.05%, at a temperature of 22 ° C and exposure for 10 minutes. The virucidal effect is manifested at a concentration of 0.01-1%. Effective against pathogens of sexually transmitted infections - gardnerelez, genital herpes; gram-positive and gram-negative bacteria - Treponema spp., Neisseria gonorrhoeae, Trichomonas spp., Chlamidia spp., Ureaplasma spp. He acts on acid-resistant forms of bacteria, microbial spores, fungi. It is stable, after processing the skin (hands, surgical field) it remains on it in a certain amount, sufficient for the manifestation of a bactericidal effect. It remains active (although slightly reduced) in the presence of blood, pus, various secrets and organic substances.

Dexpanthenol or its derivatives belong to the B vitamins, are derivatives of pantothenic acid. It plays an important role in the processes of acetylation and oxidation, participates in carbohydrate and fat metabolism, in the synthesis of acetylcholine, corticosteroids, porphyrins. It has a pronounced effect on the formation and function of epithelial tissue, has some anti-inflammatory activity (http://www.vidal.ru/poisk_preparatov/act_303.htm).

Escin is a triterpene glycoside (saponin) from the fruits (seeds) of horse chestnut (in the form of sodium salt). It has a pronounced capillaroprotective activity, has an antiexudative effect (http://www.vidal.ru/poisk_preparatov/act_23.htm).

D, L-pyrrolidone carboxylate N-cocoyl ethylarginate is a cationic surfactant that is used as an antimicrobial and conditioning agent (http://ajinomoto.ru/ru-ru/%d0%bf%d1%80%d0%be%d0%b4% d1% 83% d0% ba% d1% 82% d1% 8b /% d1% 81% d1% 8b% d1% 80% d1% 8c% d1% 91% d0% b4% d0% bb% d1% 8f% d0 % ba% d0% be% d1% 81% d0% bc% d0% b5% d1% 82% d0% b8% d1% 87% d0% b5% d1% 81% d0% ba% d0% b8% d1% 85 % d1% 81% d1% 80% d0% b5% d0% b4% d1% 81% d1% 82% d0% b2 / cae.aspx).

 Deoxyribonuclease (DNase) has the ability to hydrolyze the DNA of herpes viruses, adenoviruses and other DNA-containing viruses without damaging the DNA of the cells of the macroorganism. Ribonuclease (RNAse) has the ability to hydrolyze the RNAs of influenza viruses, parainfluenza, tick-borne encephalitis and other RNA-containing viruses, without damaging the RNA of the cells of the macroorganism. Thuja extract has a pronounced anti-inflammatory and antimicrobial effect.

To prepare the composition, use is made of: substances with a basic substance content of at least 97%, extracts with an extractive substance content of at least 40% and enzyme substances: “Deoxyribonuclease”, “Ribonuclease”, “Lysozyme”, “Collagenase”.

Deoxyribonuclease, ribonuclease, lysozyme and collagenase in the form of these preparations are not used for the treatment and prevention of viral and bacterial infections due to their difficult absorption and low level of consumer properties, as well as the lack of stability when the moisture content is over 10% and in solution, with the loss of enzyme activity in during the day.

It was unexpectedly discovered that lysozyme, deoxyribonuclease, ribonuclease, collagenase can be included in a stable pharmaceutical composition while maintaining the activity of these enzymes for a long time, despite the fact that such a composition contains a significant amount of water (up to 90%).

The pharmaceutical composition of the present invention is usually prepared by conventional methods using solid or liquid acceptable carriers or excipients selected from emulsifiers, dispersants, preservatives, flavorings, pH adjusters, polymer carriers and other excipients that are suitable for preparing the compositions. The pharmaceutical composition of the present invention can be prepared in the form of a gel, cream, patch, cream gel, paste, drops, suppositories, ointments and the like.

Additional advantages of this composition are high stability, pronounced antibacterial and antiviral effects, the ability to quickly penetrate biological barriers and, accordingly, rapid absorption, ease of use, as well as ease of dosing.

The rapid penetration is due to the binding of enzymes and other functional ingredients to carriers that are used in medicine as part of drugs, for example Reaferon-EC-lipint.

In addition, the active ingredients can be used in combination with one or more anti-inflammatory ingredients, such as D-panthenol, chlorhexidine, D, L-pyrrolidone carboxylate N-cocoyl ethylarginate, thuja extract, escin and glycyrrhizic acid, providing an additional advantage of the claimed composition.

The claimed pharmaceutical composition has stability with respect to the activity of the enzymes included in its composition during long-term storage, which is achieved by immobilizing the enzymes on carriers contained in the composition. As these carriers, any compounds capable of binding to enzymes to form enzyme-carrier complexes can be used. Examples of such carriers are liposomes, β-cyclodextrins, including hydroxypropyl-β-cyclodextrins, silicone quaternium-16, guarhydroxypropyltrimmonium chloride, polyquaternium, palmitoylhydroxypropyltrimmonium amylopectin / glycerin crosspolymer, xanthan gum, carrageenate, modified acrylic thickener 7, hydroxymethyl 7, hydrochloridextroxy 7, hydroxide 7 -9850; 7-9900), DC silicone fluid Q7-9120 (Q-9180), DC Silmogen carrier, DC ST-Elastomer 10 and other silicones PDMS structures, fullerenes, etc. The advantages of liposomes, xanthan gum and carrageenate, adge silicone-based willows (DC 7-9700; 7-9800; 7-9850; 7-9900), DC silicone fluid Q7-9120 (Q-9180), DC Silmogen carrier, DC ST-Elastomer 10 and other silicones PDMS structures are high biocompatibility. The advantages of quaternium-16, guar hydroxypropyltrimmonium chloride, polyquaternium, palmitoylhydroxypropyltrimmonium amylopectin / glycerin crosspolymer, modified acrylic thickener, hydroxypropyltrimmonium maltodextrin crosspolymer are the presence of a pronounced positive charge. This determines the antimicrobial properties of these polymers, determines a high affinity for enzymes, amino acids and anions of triterpene acids, and the ability to increase the stability of the complex with enzymes. An additional carrier is hydroxypropyl-beta-cyclodextrin, which helps to increase the solubility of derivatives of lysine, proline, triterpenic acid and create a stable conformation of the active center of the enzymes, which determines their high activity.

This provides a comprehensive antiviral, antimicrobial and anti-inflammatory effect of the claimed composition.

The present invention is illustrated by the following examples.

EXAMPLE 1

The pharmaceutical composition in the form of an ointment for the nose has the following composition, in wt.%:

L-y-glutamyl-cysteinyl-glycyl-proline 5.00 Lysine glycyrrhizinate 5.00 Deoxyribonuclease 5.00 Silicone Quaternium-16 5.00 Hydroxypropyl Beta Cyclodextrin 5.00 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 5.00 Escin 5.00 Emulsifier 5.00 Preservative 1.00 PH regulator 1.00 Demineralized water Rest

The specified composition is prepared according to the following method. All components are dissolved in demineralized water, the resulting ointment is mixed, vacuum and homogenized.

EXAMPLE 2

The pharmaceutical composition in the form of an eye ointment has the following composition, in wt.%:

L-N-2,6-diamino-hexanoyl-D-glucosamine 0.001 L-y-glutamyl-cysteinyl-glycyl-proline 0.001 Lysine glycyrrhizinate 0.001 Deoxyribonuclease 0.001 Palmitoylhydroxypropyltrimmonium amylopectin / glycerin crosspolymer 5.00 Hydroxypropyl Beta Cyclodextrin 0.10 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01 Escin 0.01 Emulsifier 0.01 Preservative 0.01 PH regulator 0.01 Demineralized water Rest

The specified composition is prepared as in EXAMPLE 1.

EXAMPLE 3

The pharmaceutical composition in the form of an antiviral ointment has the following composition, in wt.%:

L-N-2,6-diamino-hexanoyl ascorbyl phosphate 0.001 N-pyrrolidine-carbomoyl-D-glucosamine 0.001 Lysine ursolate 0.001 Ribonuclease 0.001 Modified Acrylic Thickener 1,0 Hydroxypropyl Beta Cyclodextrin 0.10 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01 Glycyrrhizic acid 0.01 Emulsifier 0.01 Preservative 0.01 PH regulator 0.01 Demineralized water Rest

The specified composition is prepared as in EXAMPLE 1.

EXAMPLE 4

The pharmaceutical composition in the form of an ointment for scars has the following composition, in wt.%:

L-N-2,6-diamino-hexanoyl-quinokithiol 0.1 N-pyrrolidine-carbomoyl-D-glucosamine 5.00 Lysine betulinate 5.00 Collagenase 0.1 Palmitoylhydroxypropyltrimmonium amylopectin / glycerin crosspolymer 5.00 Hydroxypropyl Beta Cyclodextrin 5.00 Chlorhexidine bigluconate 0.1 D-panthenol 5.00 Emulsifier 5.00 Preservative 1.00 PH regulator 1.00 Demineralized water Rest

The specified composition is prepared as in EXAMPLE 1.

EXAMPLE 5

The pharmaceutical composition in the form of an ointment for burns has the following composition, in wt.%:

Fusidoyllisine 0.001 Lysil-valil-proline will grind 2.00 Proline escinate 0.001 Lysozyme 0.001 Hydroxypropyltrimmonium maltodextrin crosspolymer 0.5 Hydroxypropyl Beta Cyclodextrin 0.10 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01 Thuja extract 0.01 Emulsifier 0.01 Preservative 0.01 PH regulator 0.01 Demineralized water Rest

The specified composition is prepared as in EXAMPLE 1.

EXAMPLE 6

The pharmaceutical composition in the form of a patch from scars has the following composition, in wt.%:

L-N-2,6-diamino-hexanoyl-usnic acid 0.1 N-pyrrolidine-carbomoyl-D-glucosamine 5.00 Lysine ursolate 5.00 Collagenase 0.1 DC Silmogen carrier 2.00 Hydroxypropyl Beta Cyclodextrin 2.00 Chlorhexidine bigluconate 0.5 D-panthenol 5.00 Emulsifier 5.00 Preservative 1.00 PH regulator 1.00 Demineralized water Rest

Plaster mass - the required amount

Spunbond Nonwoven Fabric

The specified composition is prepared as in EXAMPLE 1. The resulting mixture is treated with a non-woven Spunbond material and then a layer of plaster is applied.

EXAMPLE 7

The pharmaceutical composition in the form of a patch from scars has the following composition, in wt.%:

Betulininoillisine 0.5 N-pyrrolidine-carbomoyl-D-glucosamine 5.00 Lysine oleanolate 5.00 Collagenase 0.1 DC 7-9700 5.00 Hydroxypropyl Beta Cyclodextrin 5.00 Chlorhexidine bigluconate 0.1 D-panthenol 5.00 Emulsifier 5.00 Preservative 1.00 PH regulator 1.00 Demineralized water Rest

Plaster mass - the required amount

Spunbond Nonwoven Fabric

The specified composition is prepared as in EXAMPLE 1. The resulting mixture is treated with a non-woven Spunbond material and then a layer of plaster is applied.

EXAMPLE 8

The pharmaceutical composition in the form of a patch from scars has the following composition, in wt.%:

L-N-2,6-diamino-hexanoyl-sphagnol 0.5 Glycyl methionyl proline glycyrrhizinate 5.00 Lysine oleanolate 5.00 Collagenase 0.1 Hydrogenated Liposomes lecithins in combination with cholesterol 20,0 Methyl methacrylate 1,0 Butyl methacrylate 1,0 Hydroxypropyl Beta Cyclodextrin 3.00 Chlorhexidine bigluconate 0.1 D-panthenol 5.00 Emulsifier 5.00 Preservative 1.00 PH regulator 1.00 Demineralized water Rest

Plaster mass - the required amount

Spunbond Nonwoven Fabric

The specified composition is prepared as in EXAMPLE 1. The resulting mixture is treated with a non-woven Spunbond material and then a layer of plaster is applied.

EXAMPLE 9

The pharmaceutical composition in the form of suppositories for adhesions and bacterial infections with proctitis has the following composition, in wt.%:

L-N-2,6-diamino-hexanoyl-sphagnol 0.5 Lysil-valil-proline will grind 5.00 Lysine glycyrrhizinate 5.00 Collagenase 0.1 DC Silicone Liquid Q7-9180 2.00 Hydroxypropyl Beta Cyclodextrin 3.00 Chlorhexidine bigluconate 0.1 D-panthenol 5.00 Hydrophilic base 70.00 Preservative 1.00 PH regulator 1.00 Demineralized water Rest

The specified composition is prepared according to the following method. The hydrophilic base is melted at 40 ° C, all components are dispersed in the base. The resulting mixture is poured into molds.

EXAMPLE 10

The pharmaceutical composition in the form of suppositories for adhesions and bacterial infections with proctitis has the following composition, in wt.%:

L-N-2,6-diamino-hexanoyl-sphagnol 0.5 Glycyl methionyl proline glycyrrhizinate 5.00 Lizina will grind 5.00 Collagenase 0.1 DC ST Elastomer 2.00 Hydroxypropyl Beta Cyclodextrin 3.00 Chlorhexidine bigluconate 0.1 D-panthenol 5.00 Emulsifier 5.00 Preservative 1.00 PH regulator 1.00 Demineralized water Rest

Plaster mass - the required amount

Spunbond Nonwoven Fabric

The specified composition is prepared according to the following method. The hydrophobic base is melted at 40 ° C, all components are dispersed in the base. The resulting mixture is poured into molds.

EXAMPLE 11

The pharmaceutical composition in the form of eye drops for bacterial and viral infections of the eyes, in wt.%:

L-N-2,6-diamino-hexanoyl-isotimol 0.5 Glycyl methionyl proline glycyrrhizinate 0.01 Lysine oleanolate 0.01 Deoxyribonuclease 0.05 Carragenate 0.05 Hydroxypropyl Beta Cyclodextrin 0.1 Chlorhexidine bigluconate 0.01 D-panthenol 1.00 Emulsifier 1.00 Preservative 0.05 PH regulator 0.05 Demineralized water Rest

The specified composition is prepared as in EXAMPLE 1.

Assessment of the stability of enzymes in the compositions

Since the main disadvantage of enzymes is their instability during long-term storage of finished dosage forms based on them during the shelf life, a comparative assessment was made of the conservation of enzyme activity during storage in the form of a solution and in the form of a composition (for example, gel).

The activities of deoxyribonuclease, ribonuclease, lysozyme and collagenase were determined by the following methods.

1) Determination of lysozyme activity was carried out according to the method of OV Bukharin, based on measuring the optical density when an enzyme was added to a bacterial suspension. 0.4 ml of phosphate buffer (pH 6.2) and 0.1 ml of the test solution and 2 ml of a standardized suspension of micrococcus are poured into the test tube. The mixture was incubated for 30 minutes at 37 ° C, after which its optical density was measured on an FEK-M at λ = 540 nm.

For the unit of lysozyme activity, the smallest amount of the enzyme is taken, which, when exposed to the substrate under the experimental conditions, lyses such an amount of suspension culture of Mycrococcus lysodeikticus, which leads to an increase in optical density at a wavelength of 540 nm per unit.

2) DNA activity and RNAase activity were determined according to the Kunitz method. For a unit of activity, the DNA bases (RNA-basics) take the smallest amount of the enzyme, which, when exposed to the substrate under the experimental conditions, releases such an amount of acid-soluble products that leads to an increase in optical density at a wavelength of 260 nm per unit. 0.5 ml of substrate (DNA or RNA) and 0.3 ml of 0.2 M Tris buffer (pH = 7) are added to the control and two test tubes. 0.2 ml of the enzyme solution is added to the experimental, preheated tubes. Samples are thermostated for 30 minutes at 37.5 ° C. Then, 1 ml of 1N chilled in an ice bath is added to the samples. perchloric acid solution (HClO ₄ ), in the control 0.2 ml of the enzyme solution. The tubes are shaken and kept in an ice bath for 16-25 minutes. The precipitates formed are separated by centrifugation at 4000 rpm for 10 minutes. 0.5 ml of solution was taken from the supernatant, 2.5 ml of water was added and the absorbance was measured at λ = 260 nm.

3) To determine the proteolytic activity of papain, the modified Kunitz method was used. Such a quantity of enzyme is taken as one proteolytic unit, when exposed to casein substrate for 10 minutes under standard conditions, such a quantity of hydrolysis products is released that leads to an increase in optical density at a wavelength of 280 nm per unit.

The results are shown in the following table.

As can be seen from the table, the introduction of enzymes in the composition allows to obtain stable pharmaceutical compositions in the treatment and prevention of viral and bacterial infections. Despite the fact that upon the introduction of enzymes into the composition of such compositions, a slight loss of enzymatic activity occurs, upon further storage for 1 year, the enzymes do not change their activity due to fixation of the labile structure of the enzyme by the carrier.

Evaluation of the antiviral and antibacterial activity of the composition

To assess the antiviral and antibacterial activity, a study was conducted of the effectiveness of the composition of EXAMPLE 3 in comparison with the antiviral drug "Acyclovir" cream. The study involved 39 patients aged 18 to 45 years with clinical manifestations of herpes virus infection. By gender, the group was divided as follows: men - 11 people, women - 28 people. The duration of the disease ranged from 2 years to 12 years. At the same time, the overwhelming majority of patients had a mild and moderate course of herpes infection - 2-3 times a year - 14 people, 4-6 times a year - in 22 and 6-8 times a year in 3 patients. Among women in the observed group, orofacial manifestations were noted in 18, and genital localization in 10 people. In the group of men, 7 patients recorded genital herpes, and 4 observed had a lesion in the face area. At the same time, in 7 people (men - 2, women - 5), conditionally pathogenic bacterial flora joined the manifestations of herpes with the development of complications in the form of strepto-staphyloderma.

In most patients, a small lesion area was recorded, ranging from 0.5 to 1.0 cm in 29 people, foci of 1.5 cm in 9 patients.

The comparison group included 11 patients with manifestations of herpes infection who received external therapy with Acyclovir cream. By gender, the comparison group was divided as follows - there were 7 men, 4 women. The manifestations of herpes in all men were in genital localization, in 1 woman herpes also had genital localization, and 3 women had orofacial herpetic eruptions. According to the severity of the course, 8 patients of the control group had a mild course, 3 of moderate severity.

Before treatment and 4 weeks after the end of therapy, all patients underwent the following studies:

- Survey and inspection

- Study of material from the lesion site using polymerase chain reaction to detect human herpes simplex virus

- The study of scrapings from the urogenital tract to detect chlamydia, myco and ureaplasmas (with damage to the urogenital tract)

- Testing blood serum for syphilis; HIV test after pre-test interview

- Clinical blood test.

After obtaining informed consent for external treatment, all patients were prescribed the composition from EXAMPLE 3, 4-6 applications per day, three patients with severe course were simultaneously treated with acyclic nucleoside preparations for 5 days. In the comparison group, patients received external therapy with Acyclovir cream 6 applications per day.

Treatment was completed by 31 patients. 8 patients after remission did not appear for follow-up. Most of the observed patients (28 people) noted a good tolerance to the drug. 3 people during the use of the drug noted a fairly pronounced burning sensation after applying the cream to the foci. During the observation process, none of the patients showed allergic reactions to the composition of EXAMPLE 3.

A positive effect from the use of the composition from EXAMPLE 3 was observed in all patients and was expressed in accelerating epithelialization of foci and affecting the conditionally pathogenic bacterial flora with the resolution of infectious complications.

When examining the patients of the main group against the background of the treatment, a positive clinical effect was observed in the majority of those observed in the form of cessation of new rashes on average 3 ± 1.2 days, the beginning of epithelization on 6 ± 2.1 days, complete epithelization was observed to 11 ± 2.3 day. The timing of epithelization depended on the size of the initial focus and the severity of the course of herpetic infection. A positive therapeutic effect was also obtained in patients with bacterial complications of herpetic infection, which is probably due to the active components included in the composition. It is noteworthy that quite good results were obtained in patients with a severe course of herpetic infection, where combination therapy was carried out. Moreover, the timing of epithelialization of foci in these patients was comparable with a group of patients with mild herpes.

In the group of patients where Acyclovir cream was used, similar results were obtained in terms of the termination of the appearance of new rashes (3 ± 1.4 days), in terms of the start of epithelization (6 ± 2.3 days), while complete epithelization of the lesion foci occurred more slowly and amounted to 14 ± 2.1 days. A general clinical examination carried out before the start of treatment did not reveal abnormalities both in the main group and in the comparison group.

Thus, a study conducted on a small group of patients allows us to draw the following conclusions:

1. It was found that the use of the composition of EXAMPLE 3 is possible in the treatment of lesions caused by the herpes virus type 1, 2.

2. The drug is well tolerated by patients.

3. Side effects were recorded in 3 patients who participated in this study, and were expressed in a burning sensation in the area of application of the composition from EXAMPLE 3, allergic reactions to the drug were not encountered during the study.

4. It is possible to use the composition of EXAMPLE 3 for bacterial complications of herpes infection, which is due to the presence in its composition of components with antimicrobial activity.

5. The use of the composition of EXAMPLE 3 promotes faster epithelialization of foci compared with the use of Acyclovir cream.

6. The composition of EXAMPLE 3 can also be used in combination therapy of patients with severe recurrent herpetic infection, while promoting faster epithelization.

Evaluation of the antimicrobial activity of the composition

The antimicrobial activity of the composition of EXAMPLE 1 was determined by serial dilution. As test microorganisms, cultures: Staphylococcus spp., Streptococcus spp., Enterococcus spp., Shigella spp., Escherichia spp., Salmonella spp., Proteus spp., Acinetobacter spp., Citrobacter spp., Pseudomonas spp. Serratia ., Klebsiella spp., Antracoides spp., Cryptococcus spp., Fungi of the genus Microsporum, Trichophyton, Nocardia, Aspergillus, Candida, Actinomycetes, protozoa: Entamoeba histolytica, Trichomonas vaginalis. A one-day culture of 1000 cells / ml was added to each tube. All cultures of microorganisms, except Microsporum, Trichophyton, Nocardia, Aspergillus, Candida, Actinomycetes, were grown in test tubes in a medium with meat and peptone broth at 37 ° C for 24 hours, and cultures of Microsporum, Trichophyton, Nocardia, Aspergillus, Candida, Actinomycetes were grown Saburo at 24 ° C for two days. Titration was started at a concentration of 10 mg / ml (1/10 dilution). As a control, a test tube was used, into which only nutrient medium and microorganism were introduced. The concentration in the last tube with no growth was taken as the minimum inhibitory concentration. To assess the bactericidal effect (minimal inhibitory concentration), from the test tubes with the lack of growth, they were reseeded into plates with meat and peptone broth. The cups were thermostated at 37 ° C for a day. Bactericidal action was noted in the absence of growth on a solid nutrient medium.

As can be seen from table 2, the minimum inhibitory concentration is: for Staphylococcus spp., Streptococcus spp., Enterococcus spp., Shigella spp., Escherichia spp., Salmonella spp., Proteus spp., Acinetobacter spp., Citrobacter spp., Pseudomonaspp ., Serratia spp., Klebsiella spp., Antracoides spp., Cryptococcus spp. - 12.5 mg / ml; for Microsporum, Trichophyton, Nocardia, Aspergillus, Candida, Actinomycetes, Entamoeba histolytica, Trichomonas vaginalis - 25 mg / ml; the minimum inhibitory concentration is: for Staphylococcus spp., Streptococcus spp., Enterococcus spp., Shigella spp., Escherichia spp., Salmonella spp., Proteus spp., Acinetobacter spp., Citrobacter spp., Pseudomonas spp., Serratia Klebsiella spp., Antracoides spp., Cryptococcus spp. - 25 mg / ml; for Microsporum, Trichophyton, Nocardia, Aspergillus, Candida, Actinomycetes, Entamoeba histolytica, Trichomonas vaginalis - 50 mg / ml. Similar results were obtained in determining the antimicrobial activity of the compositions of EXAMPLES 2-11.

Evaluation of the effectiveness of the composition against influenza virus

To assess the effectiveness of the composition, a study was conducted of the composition of EXAMPLE 3. The study involved 50 patients aged 18 to 50 years with clinical manifestations of influenza. 25 patients were intranasally injected three times a day with the composition of EXAMPLE 3, 25 patients were given symptomatic treatment. In this study, the following clinical effects of the composition from EXAMPLE 3 were identified: acceleration of the relief of fever was noted and prevalence of a critical type of temperature decrease in all age groups (on average in 53% of patients). This effect is explained by the antiviral effect of the composition and is confirmed by a reduction in the duration of detection of viral antigen in smears from the nasal mucosa. The duration of a runny nose and cough is significantly reduced. The marked clinical efficacy of the composition of EXAMPLE 3 was accompanied by a protective effect against subsequent diseases for 6 months. The number of episodes of influenza per patient observed was 3 times less in the treatment of the composition of EXAMPLE 3. An important advantage of therapy with the composition of EXAMPLE 3 was the prophylactic effect on the layering of the secondary bacterial flora: complications were significantly less common in the patients of the composition of EXAMPLE 3 (23, 7%) in contrast to the comparison group (45%) (p <0.05). Evaluation of the transformation of the form of rhinitis into purulent significantly confirmed the indicated effect - 7.9% against therapy with the composition of EXAMPLE 3 and 20% - comparison group.

Evaluation of the antiviral effect of the composition of EXAMPLE 3 was carried out on the basis of PCR diagnostics carried out on days 1-2 and 5-6 of the disease. In half of the patients receiving the composition from EXAMPLE 3, an etiological agent was not detected on the 5-6th day of the disease, while in the placebo group in a third of patients (p <0.05).

Similar data were obtained in the study of the compositions of EXAMPLES 1-2, 4-11.

Thus, based on the data obtained, it can be concluded that the antiviral effect of the compositions of EXAMPLES 1-2, 4-11 against influenza virus.

Claims (4)

1. A pharmaceutical composition having antiviral and antibacterial activity, including, in wt.%:
LN-2,6-diamino-hexanoyl-D-glucosamine 0.001 Ly-glutamyl-cysteinyl-glycyl-proline 0.001 Lysine glycyrrhizinate 0.001 Deoxyribonuclease 0.001 Palmitoyl hydroxypropyltrimmonium amylopectin / glycerin crosspolymer 5.00 Hydroxypropyl Beta Cyclodextrin 0.10 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01 Escin 0.01 Emulsifier 0.01 Preservative 0.01 PH regulator 0.01 Demineralized water Rest 2. A pharmaceutical composition having antiviral and antibacterial activity, including, in wt.%:
LN-2,6-diamino-hexanoyl ascorbyl phosphate 0.001 N-pyrrolidine-carbomoyl-D-glucosamine 0.001 Lysine ursolate 0.001 Ribonuclease 0.001 Modified Acrylic Thickener 1.00 Hydroxypropyl Beta Cyclodextrin 0.10 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01 Glycyrrhizic acid 0.01 Emulsifier 0.01 Preservative 0.01 PH regulator 0.01 Demineralized water Rest 3. A pharmaceutical composition having antiviral and antibacterial activity, including, in wt.%:
LN-2,6-diamino-hexanoyl-quinokithiol 0.001
N-pyrrolidine-carbomoyl-D-glucosamine 0.001 Lysine betulinate 0.001 Collagenase 0.1 Palmitoyl hydroxypropyltrimmonium amylopectin / glycerin crosspolymer 5.00 Hydroxypropyl Beta Cyclodextrin 5.00 Chlorhexidine bigluconate 0.1 D-panthenol 5.00 Emulsifier 5.00 Preservative 1.00 PH regulator 1.00 Demineralized water Rest 4. A pharmaceutical composition having antiviral and antibacterial activity, including, in wt.%:
Fusidoyllisine 0.001 Lysil-valil-proline will grind 2.00 Proline escinate 0.001 Lysozyme 0.001 Hydroxypropyltrimmonium maltodextrin Crosspolymer 0.50 Hydroxypropyl Beta Cyclodextrin 0.10 D, L-pyrrolidone carboxylate N-cocoyl ethylarginate 0.01 Thuja extract 0.01 Emulsifier 0.01 Preservative 0.01 PH regulator 0.01 Demineralized water Rest