Vaccine for prophylaxis and immunotherapy of human and animal diseases caused by pathogenic and opportunistic gram-negative microorganisms of intestine group and their exotoxins and method for its preparing (variants), immunoglobulin preparation (variant) and method for its preparing, immunobiological preparation polycomponent vaccine

FIELD: biotechnology, microbiology, medicine, veterinary science.

SUBSTANCE: for preparing vaccine toxigenic strains of S. dysenteriae R-forms are grown, cells are subjected for lysis by treatment with chloroform, mixture is centrifuged and prepared supernatant is treated with saturated monobasic carboxylic acid or their derivatives and pH value is brought about to 3.0-5.0. Mixture if centrifuged and precipitate containing corpuscular antigens and shigellosis exotoxin are obtained. Precipitate is dissolved in buffer and pH value is brought about to 7.5-9.0. Then formalin is added in the amount 0.4-0.8% of the solution volume, or benzoic acid or benzoic acid salts are added in the amount 0.07-4.0% of the solution volume, or a mixture consisting of formalin and benzoic acid or benzoic acid salt solutions in the amount 0.10.3% and 0.03-2.5% of the solution volume, respectively. The solution is kept at temperature 30-60°C for 2 h - 60 days to provide the conversion of exotoxin to anatoxin and vaccine is prepared. Another variant of the claimed invention involves additional treatment with formalin or benzoic acid or benzoic acid salts to provide conversion of exotoxin to anatoxin, vaccine is prepared followed by its bagging and corking. For preparing immunoglobulin preparation animals are immunized with vaccine prepared by abovementioned methods followed by taking off blood, milk and/or colostrums, and/or blood, immunoglobulin fraction is prepared, sterilized, bagged and corked. This preparation is a component of the immunobiological preparation. The immunobiological preparation comprises the immunoglobulin preparation and at least one component taken among the following row: human and/or animal immunoglobulin preparations, lactoferrin, enzymes, inhibitors of proteolytic enzymes, human and/or animal normoflora preparations, yeast, vitamins, vitamin-like substances, human and/or animal proteins of acute phase, human and/or animal cytokines, higher plants components, lower plants components, components of natural origin products, apiculture products, enterosorbents, antibiotics, antibacterial chemopreparations, sulfanilamide drugs, antibacterial, anti-tuberculosis, antiviral preparations, antifungal antibiotics, synthetic antifungal preparations, stimulators of metabolic processes, antioxidants, mineral supplements, carbohydrates, lipids, replaceable and/or essential amino acids, organic acids, alkaloids, glycosides, taste supplements, aromatic supplements, base for suppositories, base for ointment formulations, technological additives for tableting, or their mixture. Invention provides preparing preparations eliciting antigenic activity with respect to broad species of pathogenic and opportunistic gram-negative microorganisms of intestine group and their exotoxins and therefore eliciting with prophylactic and curative effect with respect to diseases causing with these microorganisms.

EFFECT: improved preparing method, valuable properties of vaccine.

13 cl, 112 ex

 

Group of inventions relates to biotechnology, medicine, veterinary medicine and can be widely used in the manufacture of vaccines against pathogenic and conditionally-pathogenic gram-negative microorganisms of the intestinal group, immunoglobulin and immunobiological preparations, for the treatment, prevention, as well as in the production of food, animal feed and dietary supplements.

It is known that the basis of the pathogenesis of diarrhea that accompany the course of clientele, dysentery, Salmonella and gastroenteritis caused by Proteus and other gramatically microorganisms of the intestinal group, is the impact of excreted pathogens listed infections exotoxins (neurotoxins), with enterotoxicity activity and having immunochemical affinity for thermolabile antigen among themselves and with choleragen. Differences in pathogenic manifestation of these diseases largely depend on the selection of exotoxins by these organisms (Gabidullin SG, Zhukov S.L., Ezepchuk J.V., Bondarenko V.M. //IMEI. - 1989. - N12. - p.14-16; Jawetz E., Miller JL, Heidelberg E.A. Guide to medical Microbiology. TRANS. from English. - M.: Medicine, 1982. - Vol.2. - 384 S.; Ivanov NR, V. Ermolov Immune milk preparations and their use in acute intestinal infections in children. - Saratov: Publishing house in the Saratov University, 1985. - 120 S.; kusakina NB, Karavaeva LT, Japaridze mathematical SCIENCES. Prevention of especially dangerous infections. - M., 1977. - p.51; Korotayev A.I., Babichev S.A. Medical Microbiology, immunology and Virology. - S.-Petersburg: Special literature. - 1998. - 592 C.; Medical Microbiology. Ed. Amorally and Websajtova. - S.-Petersburg. - 1999. - part 1. - 272 S.; Fedorov, YU.N... Brylin A.P., Dostalova M.I. //Agricultural biology. - 1988. - N5. - s-124; Acres S. //J.Dairy Sci. - 1985. - vol.68. - N1. - p.229-256; C. Barber, Eyian E., Keyelar Y. //Rev. Immunol. - 1969. - vol.33. - p.101; Climents J., Finkelstein R. //Infect. Immun. - 1978. - vol.22. - N3. - p.709-713; Mulezyh M, Adamus G., Witnowska D., Romanowska E. //Arch.Immunol.Ther.Exp. - 1981. - vol.29. - p.85; Mulles W., Schlecht, S., Westphal O. // Zbl. Bakt.Hyg.I.Abt.Orig.A. - 1980. - vol.64. - p.248; O'brien A.D., Chen M.E., R.K. Holmes ct al. //Lancet. - 1984. - vol.14. - p.77-78; Supotnitski MV - Organisms, toxins and disease. - M.: Higher school book. - 2000. - 376 S.).

Experimentally proved, that immunity against enteropathogenic Escherichia coli, Shigella and other gram-negative organisms is largely determined by the presence of antitoxic antibodies in the first place, to thermolabile component of exotoxin (P. Vartanian, Severtsev, M.K., Stanislavsky Y.S.// IMEI. - 1980. - N8. - p.87-90; L. Emody, Ketyi I., Kuch Century, Pacsa S. //Acta Sci Hung. - 1979. - vol.26. - N3. - p.223-241; F. Klipstein, F. Engert, H. Sort //Infect. Immun. - 1980. - vol.28. - N1. - p.163-170). The severity of antitoxic immunity depends on many factors, particularly on the immunogenicity of the Academy of Sciences of the toxins. For example, the exotoxins of different Shigella species immunogenetic related, but only exotoxin S.dysenteriae 1 has the strongest cytotoxic properties, and received from him the toxoid pronounced immunogenicity. On the one hand, this is due to the fact that the exotoxin type S.dysenteriae (Shiga-toxin - old, but still used the name) has a higher molecular weight, on the other hand, produced S.Sonnei and S.Flexneri exotoxins are produced in more than 1000 times smaller quantities. Therefore, as the cross-reactive and specific antibodies are more pronounced after vaccination animals Shiga-toxoid (Supotnitski MV Microorganisms, toxins and disease. - M.: Higher school book. - 2000. - 376 S.; Golubev I., Kilesa VA, Kiseleva BS and other Enterobacteria: a guide for physicians. - M.: Medicine, 1985. - 321 S.; kusakina NB, Epstein-Litvak W., Kokorina T.A. //BABIM., - 1971. - N2. - p.70; Timakov E, Peter V.G., Bondarenko V.M. Biological and genetic characteristics of bacteria of the genus Shigella. - M.: Medicine. - 1980. - 296 S.; Keusch G.T., lacewicz M. //J.Infect.Dis. - 1977. - vol.135. - p.551; O'brien A.D., M.K. Thompson, P. Gemski, Doctor, B.P. et al. //Infect.Immun. - 1971. - vol.15. - p.796).

Comparative immunochemical analysis corpuscular antigens of gram-negative coliform, first of all, enterobacteria, also shows significant antigenic relationship given what's microorganisms. Education chromosomal hybrids between E. coli and Salmonella and Shigella indicates a very high degree of genetic homology data of bacteria, which is confirmed by comparison of chromosome maps. Of particular note is the relationship of E.Coli and Shigella. The genomes of these organisms related to 85-90%. A high degree of similarity of genomes leads and high affinity antigenic properties of strains of Shigella and E. coli, which finds expression in the presence of cross-reactions with diagnostic agglutinating sera. It is important to note that the antigenic composition of most of the pathogenic microorganisms of the intestinal group of humans and animals is similar (I. Golubeva, Kilesa VA, Kiseleva BS etc. - Enterobacteria: a guide for physicians. - M.: Medicine, 1985. - 321 S.; Korotayev A.M., Babichev S.A. Medical Microbiology, immunology and Virology. - S.-Petersburg: Special literature. - 1998. - 592 C.; Medical Microbiology. //Edited Amorally and Websajtova. - S.-Petersburg. - 1999. - part 1. - 272 S.; Medical Microbiology. //Edited Weaponammo and Osceola. - M.: GEOTAR Medicine, 1999. - 1200 S.; Mikhailov, NV //Mater. The Intern. The international Symposium., dedicated to the year Laster. - S.-Petersburg, 1995. - p.66; Stanier R., Edelberg E., Ingram, J. The world of microbes. TRANS. from English. - M.: Mir, 1979. - v.3. - 486 S.).

A big problem for medicine are zoonotic who - infection common to man and animals (Makarov V.V., A.A. Vorobyov //IMEI. - 1999. - N4. - s-115). Up to 70% of all diarrhoeal diseases in children under 5 years of age have food etiology. For example, the incidence of salmonellosis in some European countries up to 300 cases per 100 thousand population with a mortality of 3%. In recent years in many developed countries (USA, Canada, UK, Japan and others) colibacteriosis animals is under scrutiny veterinary and medical professionals, and who, as an important role in infectious diseases of man began to play Escherichia producing Shiga-like toxin or verotoxin (VTEC), in particular serovar E. coli 0157:H7 (ECO). In Russia, the situation is even more acute (Golubeva IV, Kilesa VA, Kiseleva BS etc. - Enterobacteria: a guide for physicians. - M.: Medicine, 1985. - 321 S.; Golutva NICHOLAS, Hasenson LB, Safonova NV //Materminding., dedicated to the year of Pasteur. - S.-Petersburg. - 1995. - p.53; Kulik A.V., Panin A.N., Sosnina VV //veterinary medicine. - 1997. - N3. - s-27; Makarov V.V., A.A. Vorobyov //IMEI. - 1999. - N4. - s-115; Medical Microbiology. //Under redviper and Osceola. - M.: GEOTAR Medicine, 1999. - 1200 S.; Sergounin VI //Epidemiology and infectious diseases. - 1974. - N4. - p.32-34; Stanier R., Edelberg E., Ingram, J. The world of microbes. TRANS. from English. - M.: Mir, 1979. - v.3. - 486 S.; HO Consultation on Selected Emerging Foodbome Dis. //WHO/CDS/VPH. - 1995; Zoonoses. //WHO Veterinary Public Health Unit. Publications and Documents. - 1995).

As follows from the analysis, there are currently no domestic and imported vaccines containing shellene toxoids, in addition, the domestic industry does not produce shellene vaccine (Medunitsyn NV Vaccinology. - M., "Triada - X", 1999, 272 S.).

In earlier sources mentioned dysentery vaccine of S.Flexneri or S.Sonne and Depakine of them (Guide to vaccine and serum case. - //Ed Pinboliada. M: "Medicine", 1978, 440 S.). However, these vaccines have not found application in practical medicine, because due to the lack of toxoid after vaccination in humans are not produced antitoxic antibodies, in addition, has a low immunogenicity of drugs.

Thus, the prior art not known to the vaccine and its preparation, which would contain Shelley toxoid and toxoids used to treat and prevent a wide range of diseases caused by conditionally pathogenic and pathogenic gram-negative microorganisms of the intestinal group.

In veterinary medicine developed poly-specific hyperimmune serum against Rota-, corona-, herpes viruses, and E. coli (99, 20) for local protection and immunotherapy mixed forms of diarrhea of newborn calves (Patent RU 2043772, 20.09.95; Patent RU2054289, 20.02.96; Patent RU 2086236, 10.08.97). This drug does not possess antioxidant activity and does not contain antibodies to Shigella.

In the United States a patented method of obtaining immune drug, derived from milk and colostrum immune cows and having the activity to the entero-pathogenic to humans and farm animals (U.S. Patent N4402938, class A 61 K 39/00, 1983; application Germany N3924420, class A 61 K 35/20, 1991).

In our country in medical practice there are two oral immunoglobulin preparation derived from immune colostrum cows, so - called immune lactoglobulin (name, settled in Russia): against opportunistic bacteria and Salmonella (Medunitsyn NV Vaccinology. - M., "Triada-X", 1999, 272 S.; Sobolev, S.V. //abstract. Diss. in the form of a scientific report...], dokt. - Rostov-on-don, 1991. - 38 C.) and against Escherichia coli and Proteus (Medunitsyn NV Vaccinology. - M., "Triada-X", 1999, 272 S.; Sobolev, S.V. //Autoreplies. in the form of a scientific report...], dokt. - Rostov-on-don, 1991. - 38 S.; Sobolev, S.V., V. Ermolov, Valence V.E., etc. //Sat. "Topical issues of immunology, Allergology and molecular biology". - Krasnodar, 1987. - t. - p.119-121; Sobolev, S.V., Mineeva L.D., Rabinovich E, Fedorov T.A. //J. of Microbiol. - 1989. - N8. - p.7-12).

As shown by the analysis of the prior art in respect of immunoglobulin PR the preparations in the literature there is no information about the immunoglobulin preparations containing antibodies to any of the toxins of pathogenic gram-negative microorganisms Escherichia groups and Shigella. All known immune immunoglobulin preparations are composed of antibodies only to the cell wall of microorganisms.

The closest technical solution to the immunoglobulin preparation and method of its production will be protivokomarinye lactoglobulin, which represents an immunoglobulin product obtained by immunization of cows, intake of colostrum, receiving immune serum (Ivanov NR, V. Ermolov Immune milk preparations and their use in acute intestinal infections in children. Saratov. Ed. Sarat. u-TA, 1985, p.35-44). The disadvantage of this immunoglobulin preparation is a low specific activity, the absence of antitoxic antibodies and antibodies to Shigella, which is confirmed experimentally on live models.

Objective of the claimed invention is the creation and production of high-efficient and non-lethal vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, creating immunoglobulin preparations, the region is non therapeutic and preventative effects against diseases of man and animals, caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, creation of immunobiological preparations with therapeutic and preventive effects against a wide range of diseases of internal and external organs of humans and animals caused by various pathogenic and conditionally-pathogenic gram-negative and gram-positive microorganisms and their toxins, viruses, fungi, protozoa, helminths.

This object is achieved in that for obtaining vaccines for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins grow toxigenic strains R-forms S.dysenteriae, produce lysis of the cells by treatment with chloroform, centrifuged, then the supernatant is treated with the utmost monobasic carboxylic acids and their derivatives, such as trichloroacetic acid, Caprylic acid to a pH of 3.0 to 5.0, centrifuged to obtain a precipitate containing particulate antigens and Shelley exotoxin, dissolve the sediment in the buffer to obtain a solution pH of 7,5-9,0 add formalin in the amount of 0.4-0.8% of the amount of solution, or benzoic acid, or salts of benzoic acid in which Alceste 0.07 to 4.0% of the quantities, or their mixture, and the amount of formalin is 0.1-0.3% of the amount of solution, the amount of benzoic acid or its salts of 0.03 to 2.5% of the amount of the solution, maintain the solution at a temperature of 30-60°C for 2 hours to 60 days before the transfer of exotoxin in the toxoid with receipt of the vaccine. Before packaging the vaccine can be subjected to freeze drying to obtain granules and powders. Before filling in the vaccine can be administered ointment base or basis for suppository.

Another option this object is achieved in that for obtaining vaccines for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins grow toxigenic strains R-forms S.dysenteriae, produce lysis of the cells by treatment with chloroform, centrifuged, then the supernatant is treated with the utmost monobasic carboxylic acids and their derivatives, such as trichloroacetic acid, Caprylic acid, to a pH of 3.0 to 5.0, centrifuged to obtain a precipitate containing particulate antigens and Shelley exotoxin, dissolve the sediment in the buffer to obtain a solution pH of 7,5-9,0, add formalin in an amount of 0.4-0.8% of the amount of solution, or benzoic acid, or a salt of benzoic acid is in the amount of 0.07 to 4.0% of the quantities, or their mixture, and the amount of formalin leaves 0,1-0,3% of the amount of solution, the amount of benzoic acid or its salts of 0.03 to 2.5% of the amount of the solution, maintain the solution at a temperature of 30-60°C for 2 hours to 60 days, and then perform additional processing by the reduction in the number of free formaldehyde to 0,18-0,25% of the amount of solution, or the free benzoic acid, or its salts in an amount of 0.07 to 4.0% of the amount of solution or their mixture, and the amount of free formaldehyde is 0,037-0.12% of the quantities, and the number of free benzoic acid or its salts of 0.03 to 2.5% of the amount of the solution is maintained at 30-60°C for 2 hours to 30 days before the transfer of exotoxin in the toxoid with receipt of the vaccine, followed by filling and capping. Thus, before packaging the final product can be subjected to freeze drying to obtain granules or powders.

Before filling in the vaccine can be administered ointment base or basis for suppository.

Vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, when growing S.dyscnteriae on casein broth is treated supernatant trichloroacetic acid, obtained in setloginname ways the vaccine is a fraction Chiellini corpuscular antigens and toxoid, contains protein in an amount of 10-15 mg/ml nucleic acid 0.2 - 0.5 mg/ml lipids traces. When growing microbial cultures on other nutrient media composition of the vaccine, as the experiments showed, can vary in composition.

This vaccine can be used for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins.

To obtain immunoglobulin preparation conducting the immunization of animals with the vaccine for the prophylaxis of diseases in humans and animals caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins received the above ways, then hold the fence in animals immune milk and/or colostrum, and/or blood, receive immunoglobulin fraction. After sterilization it is possible to carry out drying.

Immunoglobulin preparation obtained above method contains a fraction of immunoglobulins G, a and M in equation (10-50):(0.01 to 5):(1-10). Studies have shown that the ratio of immunoglobulins in the product is completely dependent on the used raw material and can greatly vary depending on animal species, age, time of lactation, time of year, the ratio is and the power composition of the diet, illness, health status, genetic abnormalities, sometimes occurring in ruminants innate natural immune deficiency of IgA.

Immunoglobulin preparation may additionally contain at least one component selected from the range of: flavorings, aromatic additives, base for suppositories, the basis for ointment forms, processing additives for tableting.

Immunobiological preparation contains immunoglobulin drug and at least one component selected from the range: immunoglobulin preparations humans and/or animals, lactoferrin, enzymes, inhibitors of proteolytic enzymes, drugs normoflora humans and/or animals, yeast, vitamins, vitamin-like substances, proteins of the acute phase of human and/or animal cytokines by human and/or animal components of higher plants, components of lower plants, components of natural products, bee products, chelators, antibiotics, antimicrobial drugs, sulfa drugs, antimicrobial and antiparasitic drugs of natural origin, anti-TB drugs, antiviral drugs, antifungal antibiotics, synthetic antifungal drugs, stimulants metabolite is of such processes, antioxidants, mineral supplements, carbohydrates, lipids, interchangeable and/or essential amino acids, organic acids, alkaloids, glycosides, flavorings, aromatic additives, base for suppositories, the basis for ointment forms, processing additives for tabletting or their mixture.

This immunoglobulin preparations of human and/or animal selected from the range: the fraction of immunoglobulins, immunoglobulin G, immunoglobulin a, immunoglobulin M, immunoglobulin T, fragments of immunoglobulins.

The enzymes selected from the range: lactoperoxidase, lysozyme, trypsin, chymotrypsin, himopsina, turrilites, tridecane, ribonuclease, desoxyribonuclease, collagenase, esperaza, isoamylase, profesin, karipazina, pepsin, gastric juice natural, peptidyl, abomin, Pancreatin, Oraza, soliton, amilase, nicedata, panzino Forte, anchorman, festal, digital, enzistal, Mezim Forte, lydasum, ronidase, cytochrome C, penicillinase.

Proteolysis inhibitors selected from the range: pantripin, ingitril, contrical, gordox.

Drugs normoflora human and/or animal selected from the range: bifidobacteria, lactobacilli, streptococci, strains hepatogenous Escherichia coli, Saccharomyces cerevisiae.

Yeast are selected from a number of: yeast, bakery yeast.

Vitamins are selected from a series: A, b, D, K, P, PP, U, E, calcium Pantothenate, Punta ethanol is ol.

Vitamin-like substance selected from the range: methylmethanesulfonate chloride, calcium pangamat, choline chloride, lipoic acid, lipemic, orotic acid, pangamic acid, p-aminobenzoic acid, Inositol, carnitine.

Proteins of the acute phase of human and/or animal selected from the range: haptoglobin, α-fetoprotein, orosomucoid, ceruloplasmin, C-reactive protein, α1-antitripsin, α1-antichymotrypsin, Gc-globulin.

The cytokines selected from the range: the interferon (if), interleukins (IL), tumor necrosis (TNF), transforming growth factor - β (TFFβ), colony-stimulating factors (CSF), factor suppressing leukemia (LIF), CD95.

Fractions representing the tinctures and/or extracts and/or herbal teas, and/or pomace and/or powder of higher plants, selected from the range: aloe, Althea officinalis, orange, Manchurian aralia, apricot ordinary, American agave, adenoma Indian, calamus swamp, ajowan fragrant, acanthopanax's broom, acacia, alpinia drug, amaranth solosicily, pineapple real andrografis paniculate, anemarrhena asphodelaceae, Chinese Angelica, anise ordinary, peanut underground, watermelon is edible, Areca amniotic, chokeberry Aronia, prickly artichoke, Astragalus, sherstystovustyi atractylodes ovate, marsh rosemary, bergenia, anise Nast is ASCII, Basil ordinary, banana cultural, Amur velvet, Baranets, common barberry, birch, immortelle, blumea Solomona, beans, vegetable, cow-parsnip cut, boswelia sacred, hawthorn, bilberry, Boudreau plyuschevidnaya, Sambucus nigra, cap drug, borage drug, setwell, vanilla, cornflower blue, almond trifoliata, loosestrife common verbena drug, Veronica officinalis, grapes cultural, wool hypnotic, cherry, thoroughwax sickle, thistles curly, varanka drug, elm rusty, Gardenia razminovicha, harpagophytum open, fragrant cloves, gedai crowned, geranium meadow, hibiscus Syrian, gingko bilobed, blueberry forest, homalomena fragrant, knotweed, rough gentian, garden pea, hydrangea panicle, Adonis, the mountain woman, pomegranate, grapefruit, buckwheat sowing, pear ordinary, guarana cupana, Houttuynia cordate, elecampane, Chinese Wolfberry, Dioscorea hairy, clover medicinal, oak, oregano, Angelica, BlackBerry PPE, canadian Hydrastis, ginseng, honeysuckle Altai, devil high, zanthoxylum pepper, starwort medium, St. John's wort, strawberry, strawberry, goldenrod, solotica the nick ordinary, sweet grass sweet, white willow, ginger, Imperata cylindrical, figs ordinary, hyssop drug, milkwort Seneca, yohimbe, cocoa present, calendula officinalis, cranberry tree, capers prickly, cabbage, cardamom real, potatoes, Senna leaves, horse chestnut, dogwood drug, clover, cress seed, claparon Daur, strawberry, cranberry marsh, Cola brilliant, condurango, coriander seed, mullein postively, this thicket cinnamon, Catnip cat, coffee tree, nettle, Burnet drug, buckthorn laxative, ordinary corn, turmeric, meadowsweet, lavender, spike, Laurel, Potentilla goose, quinoa spreading, leuzea carthamoides, flax seed, lespedeza kopeckova, lespedeza capitate, hazel ordinary, lemon, lemongrass Chinese, Leander celeberity, lime sertselystoyi, burdock, Lotus orehonosny, onion, smellage, alfalfa seeding, oregano, poppy-Samoseiko, raspberry, mallow forest, mango IPM, Mandarin Chinese, European olive, the mother-and-Macia ordinary, mate, madder dyeing, balm, myrobalan, myrrh tree, juniper ordinary, MOMORDICA cochinchina, Morinda L. the drug, carrots sown, seaweed, peppermint, sea-buckthorn-buckthorn, oats, dandelion, walnut, walnut, nutmeg, digitalis, fenugreek, papaya, passion fruit meat-red, shepherd's purse, male fern, allspice, pepper water, Kava pepper, Cayenne pepper, pepper cubeba, black pepper, Javanese, peach ordinary, parsley garden, common tansy, pinellia trigeminal, the peony, Siberian fir, pluchea Indian, Japanese dodder, plantain, sunflower ordinary, wormwood, bitter orange, renal tea, Psoralea Liminality, Leban, Pueraria blade, motherwort heart, pfaffia, soft wheat, Elytrigia repens, milk Thistle, rhubarb, radish crop, Romania Chinese, shepherd's purse, rice seed, Rhodiola rosea, rye, rosemary herbal, chamomile, crabgrass rotundifolia, mountain ash, sarsaparilla Chinese, the ordinary beet, celery odorous, Senna, Serenoa creeping, sid home, black currant, red currant, Golden currant, goutweed ordinary, licorice, malt, Salsola Collina, saw-wort Rapaniana, Sophora, soybean, asparagus medicinal, harrow plough, tablelist facilitatively, stevia, stenoma tuberous, sterck the lia, cottonweed marsh, syt round, sumac tanning, tamarind Indian, Thistle prickly, turn, thermopsis, common bearberry, Jerusalem artichoke, black poplar, mulberry tree, cumin ordinary pumpkin, yarrow, fennel garden, jujube, Uncaria hairy, kidney beans, fennel, physalis ordinary, forsize hanging, horsetail, hops ordinary, horseradish, chrysanthemum Indian, hydrocotyl, chicory ordinary, ordinary thyme, Alisma Plantago-Aquatica, a series of tripartite, cherry, bilberry, garlic seed, chiriboga, betony bouquinistes, Salvia officinalis, Shandra ordinary, saffron, seed, rosehip cinnamon, Scutellaria baicalensis, spinach vegetable, sorrel curly, eucalyptus, eucommia vyazolistny, Eleutherococcus senticosus, Elsholtzia Patrina, Emblica drug, Echinacea, Yucca, Apple, ash, barley ordinary.

Fractions representing the tinctures and/or extracts and/or herbal teas, and/or pomace and/or powder of lower plants, selected from the range: white fungus, fungus varnished tinder fungus, the fungus Armillaria real, Kombucha tea (Kombucha), sugar kelp (laminaria), Maitake, ahima, Reishi mushroom, spirulina, bladder wrack, Chlorella, tsetrariya Icelandic, black birch mushroom, chaga, shiitake mushrooms.

Fractions representing infusions, and/or extracts and/or herbal teas, and/or pomace and/or powder products of natural origin selected from the series: shark cartilage, bezoar stone, beeswax, farm animals muscle powder, gelatin, bile, squid, bone, crab, shrimp, blood, animals, mussels, clams, colostrum condensed, ROE salmon, skim milk powder, condensed whey, sea urchins, ants, pantogematogen, antlers, pantocrine, genitals bear and deer, shell mollusks, fish powder, the internal organs of the sea pike, centipede, Scorpion, chitin, cartilage farm animals, earth worms, turtle armor, mule snake egg. Bee products selected from the range: propolis, honey, Royal jelly (apilak), plant pollen.

Chelators selected from the range: the preparations of activated charcoal, enterosorbent SKN, carblog, polifan, zeolites, humilit, kaolin, diatomaceous earth, montmorillonite.

The antibiotics selected from the series: drugs of the penicillin group, the group of cephalosporins, cephamycin, carbapenems, carbapenems, tetracycline, aminoglycoside antibiotics, antibiotics-macrolides, azalides, the drugs group of lincomycin, a group of drugs chloramphenicol, rifamycin, ristomycin, fuzidin, polymyxins, gramicidin, gelmicin, spectinomycin, drugs group p is promicin, group rifampicin group of cycloserine, group florimitsina, rifabutin, nystatin, levorin, amphotericin, infopyramid, mikogeptina, primycin.

Antimicrobial chemotherapeutic agents selected from a number of derivatives of 8-oksihinolina derived naphthiridine, quinolones, fluoroquinolones, derivatives finokalia, derived nitrofuran.

Sulfa drugs selected from the range: streptocid, norsulfazol, sulfazin, sulfargin, sulfadimezin, etazol, sulfatsil, ursulan, sulfapiridazin, sulfamonometoksin sulfadimetoksin, sulfalen, sulfalen-meglumin, cotrimoxazole, alginat, sulfasalazin, salazosulfapiridin, salazopiridazin, drug, mesalazine.

Antimicrobial and antiparasitic drugs of natural origin selected from the range: sodium pninat, novoimanin, sangviritrin, Umckalor, evkalimin, chlorophyllipt, hasnain, bales 2 acterized, tomicic, the flowers of calendula tincture of Sophora japonica, Allerca.

Anti-TB drugs selected from the range: isonicotinic acid hydrazide, its derivatives and analogs, derivatives, para-aminosalicylic acid, the group of drugs ethambutol, groups, pyrazinamide, group thioacetazone, group solyutizona.

Antiviral drugs are different groups selected from the range: interferon, inductors interferon, acyclovir, ganciclovir, ribamidil, who zidovudin, the idoxuridine, lamivudine, didanosine, valacyclovir, famciclovir, ribavirin, indinavir, methisazone, idoxuridine, rimantadine, adapalen, katiforis, bonafton, Arbidol, oksolina, cebrian, redoxon, prorenal, flakozid, alpizarin, Halpin, magosin, hossipole.

Antifungal antibiotics, selected from the range: griseofulvin, nystatin, levorin, levorin sodium salt, amphotericin b, infopyramid, mikogeptina.

Synthetic antifungal agents selected from the range: clotrimazole, ketoconazole, econazole, miconazole, mikozolon, isoconazole, fluconazole, bifonazole, amorolfine, Itraconazole, terbinafine, naftifine, dekamina, mikoseptin, Hirofumi, nitrofungin, acticin, Amarin.

Drugs that stimulate the metabolic processes selected from the set: methyluracil, pentoksil, potassium orotate, stronger, acid ATP, fosfaden, etagen, phosphocreatine, Riboxin, dalargin, Semax, dipromony, carnitine chloride, Mildronate, atsemin, polyethylene oxide, Katalin, quinax, filgrastim, sargramostim, molgramostim, lenograstim.

Antioxidants selected from a number of vitamins a and E, BHT, superoxide dismutase, emoxipin, Mexidol, opinon.

Mineral additives selected from a number of: calcium, potassium, sodium, iron, zinc, copper, manganese, cobalt, chromium, molybdenum, phosphorus, sulfur, magnesium, chlorine, fluorine, silicon, bromine, with the ribs, boron, vanadium, Germany.

Carbohydrates selected from the range: glucose, fructose, lactose, sucrose, maltose, inulin, starch, dietary fiber, pectin, gums, mucilages.

Lipids selected from the range: saturated and unsaturated fatty acids, almond oil, peach oil, sea buckthorn oil, rosehip oil, castor oil, corn oil, cottonseed oil, peanut oil, edible bran, sunflower oil, pumpkin seed oil, phospholipids, sterols, waxes.

Interchangeable and/or essential amino acids selected from the range of: arginine, alanine, cysteine, cystine, glutamic acid, glutamine, glycine, histidine, leucine, lysine, methionine, ornithine, Proline, phenylalanine, tyrosine, valine.

Organic acid selected from the range: Apple, lemon, hydroxylimine, castronova, tartaric, oxalic acid, salicylic acid, formic, acetic, benzoic, oxybenzone, lipoic, protectionby, pyrocatechol, Gallic, succinic, malonic, oksikorichnye, hydroxycarboxylic, sorbic, persarmenia, oxycarbonate, nicotine.

Alkaloids selected from the range: caffeine, salsali, berberine, palmatine, terrorizin, columbamine, capsaicin, viburnum, amirin, theobromine, tsepelin, xanthine, silymarin, stehekin.

Glycosides selected from the range: steroidal saponins, triterpene saponins, antraglikozida, bitter glycosides (IRI shall oidi), cardiac glycosides.

Immunobiologicheskie preparation may be a lyophilized powder, granules, capsules.

Immunobiologicheskie the drug may further comprise pharmaceutical components for tableting.

Immunobiologicheskie the drug may further comprise pharmaceutical components for the production of suppositories.

Immunobiologicheskie the drug may further comprise pharmaceutical components for the production of ointment forms.

Immunoglobulin preparation can be applied for the prevention and treatment of diseases of man and animals caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins.

Immunobiologicheskie the drug can be used for the treatment and prevention of a wide range of diseases of internal and external organs of humans and animals caused by various pathogenic and conditionally-pathogenic gram-negative and gram-positive microorganisms and their toxins, viruses, fungi, protozoa, helminths.

Multicomponent vaccine may contain at least two components, at the same time as one of the components contains a vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-patoh nimi gram-negative microorganisms Escherichia groups and their exotoxins, received the above methods.

Proof of the effectiveness of vaccines to prevent diseases of humans and animals caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins against pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins are laboratory tests on animals, cell cultures and haemagglutination reactions of vaccines and immunoglobulin preparations derived from colostrum, milk and blood immunoserologic this vaccine laboratory and agricultural animals, and clinical trials protivosudorozhnogo immune immunoglobulin preparation (protivoglistny lactoglobulin), obtained from colostrum immune cows.

If vaccination for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins obtained, antibodies to a wide range of opportunistic and pathogenic gram-negative microorganisms Escherichia groups and their exotoxins.

The experiments were conducted for comparison when checking antitoxic and antibacterial protection protivoglistnyh is the courthouse square (immunoglobulin preparations goats and cows), lactoglobulin (drugs immune immunoglobulin preparations) protivoallergennogo and against pathogenic bacteria Salmonella (on demand gisk named after. L.A. Lytvyn), non-immune drugs, and compared protivoglistnyh drugs with normal gamma globulin person.

Experiments on neutralization shallenge of exotoxin protivoleprosnami drugs and isolated from his immunoglobulin G were raised in mice and cell culture HeLa. When setting the mice were used intraperitoneal method and test swelling of the paws of the mouse.

When 2,4-2,5 LD50immune protivogelmintnye drugs in average 344 times superior to the antitoxic activity of immune milk preparations, and at 3.5 and 4.4 LD50on average 578 times. Comparing between the IgG isolated from immune and non-immune drug milk goats, the observed difference in the antitoxic activity of 2,5-3,1 LD50520 times when 3,9-4,2 LD50in 627 times. Protivogelmintnye drugs on the antitoxic activity exceeded protivokomarinye lactoglobulin in 50-400 times, the difference between the first and lactoglobulin against opportunistic bacteria and Salmonella was 166-367 times or more. Protivogelmintnye drugs exceeded the activity of the immune lactoglobulin in 140-366 time. If we take the level of antitoxic activity is immunolo drug for zero, we can say that lactoglobulin against opportunistic bacteria and Salmonella does not possess antioxidant activity, and protivokomarinye also does not have these antibodies or contains them very little.

In the test of the swelling of the paws of the mouse protivoglistny the drug completely prevented development of edema of the legs in a dose 0,093-0,187 mg, and isolated from his IgG - holding 0.062-0.125 mg, whereas with the introduction of non-drug and received IgG at a dose of 1 mg, there was complete absence of a positive effect, i.e. swelling of the legs remained. Was impossible to put the experiments with the introduction of the foot mouse weighing 10 g greater than 1 mg non-immune drugs.

When checking antitoxic activity protivosudorozhnogo immunoglobulin in HeLa cells was determined that for the neutralization of CTD100required 128-198 times less immune drug than non-immune. Moreover, when compared with antitoxic intraperitoneal test in mice cytotoxic test on HeLa cells gives more uniform from experience to experience the results.

Antibacterial protective activity protivoglistnyh drugs was tested in mice using intraperitoneal method in relation to S.sonnei, S.flexneri 2a, S.dyscnteriae 1, S.typhi and Ps.aeruginosa.

For drugs obtained from colostrum immune and non-immune goat, the difference in protective actively the tee while infecting 3-4 LD 50culture S.sonnei averaged 71.4 times. Indicator protective activity lactoglobulin calibrating against opportunistic bacteria and Salmonella was lower than 13.6-20,0 compared to protivoglistnym drug. When infected mice S.dyscnteriae 1 the difference in the protective activity between protivoleprosnami and non-immune drugs averaged 96,2 time between protivoglistnym and protivookislitelnym - 96 times, protivoglistnym and lactoglobulin against opportunistic bacteria and Salmonella - more than 76 times.

Protivogelmintnye immunoglobulin preparations on average effective protective dose against S.flexneri 2a in mice surpass immune drug when 3,2 LD50in 27-66 time, at 4.2 and 5.6 LD50- 62-75 times when 11,5-19,0 LD50- 73,8-289 times, the activity protivoglistnyh drugs above protivoallergennogo when 3,2-5,6 LD50in 17,7-36 times, when 11,5-13,0 LD50- 94-108 time between protivoleprosnami lactoglobuline drugs and normal gamma globulin difference between the 3.2 and 5.6 LD50is 27,6-40 times, activity protivoallergennogo of the drug was lower immune when 3,2 LD501.3 times and outperformed his at 11,5-13,0 LD502.6-3 times, between protivookislitelnym and gamma-globulin values oscillated in one direction or another 1.2 to 2 times.

Also experimental is but shows many advantages over protective activity protivoglistnyh immunoglobulin preparations compared with immunized against S.typhi and Ps.aeruginosa.

There were also conducted experiments on mice in comparison protective activity immunoglobulinemia preparations, obtained by immunization of cattle two kinds of vaccines. The first vaccine was obtained the above method, the second integrated vaccinal preparation included the first vaccine and vaccine preparations, obtained from strains of Shigella isolated from the various outbreaks of dysentery. The second component of the last vaccine preparation was a washout cultural mass with Petri dishes. Experiments on animals have shown that immunization of cattle with a second vaccine, as a rule, did not lead to an increase in the number of antibodies to components of the cell wall of Shigella and, of course, did not increase the antitoxic activity of immunoglobulin preparations. It is important to remember that living models are the most sensitive and accurate measure of the activity of drugs against various microorganisms.

Cross-reactions diffusion precipitation and immune electrophoresis installed antigenic relatedness of choleragen, choleragen-toxoid with exotoxins Shigella, Salmonella, Escherichia, Proteus. By cross-absorption of precipitates from sera to a vaccine containing choleragen-toxoid, and to vaccines containing toxoids derived from exotoxins ENT is nobacteria, it is found that the antigenic affinity of these drugs is associated with the exotoxins and intergeneric antigens. Cross-reactions between Shigella sonnei and Pseudomonas, Vibrio cholerae cholera and various enterobacteria showed that the antigenic relationship among gram-negative bacteria goes far beyond the intergeneric relationships.

Clinical trials conducted on 50 children suffering from dysentery sonnei and Flexner 2A, Salmonella, coli-infection caused by enterotoxigenic Escherichia coli. Assessment of clinical effectiveness protivosudorozhnogo of lactoglobulin included the timing of the disappearance of General toxic symptoms and intestinal disorders, as well as bacteriological rehabilitation. Sanitizing effect with bacteriologically confirmed enteric infections obtained as in patients with clinically severe form of the disease, and the positive cases. Normalization of stools occurred in all patients, and in a shorter time than with traditional methods of treatment. In any case, the application protivosudorozhnogo of lactoglobulin, were not required to continue etiotropic therapy. Was marked by good tolerability, no adverse reactions when used, and exacerbations of allergic skin manifestations even in children with a burdened allerg the logical history.

Formalin is the most popular reagent in the production of vaccines and anatoxins.

It is established that the introduction in preparing the vaccine substances causing her detoxification, two processes occur: the actual detoxification and stabilization of the structure of molecules of antigens with the formation of a hard link. Run different on the complexity of the chemical reaction between formaldehyde and radicals and amino groups of the protein. Still considered that to neutralize formalin most favorable conditions at pH 7,2-7,3 (established traditional values).

To date, however, our sigillata vaccine when handling formalin 70% of cases maintained a high level of toxicity or lost immunogenicity.

The first phase of the experiment consisted in keeping vaccines for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins at 37°during the year. As a end result of this continued high level of free (unbound) formaldehyde (0,074-0.12% of the amount of the solution), but the process of detoxicative vaccine has not occurred.

Then the analysis of the vaccine found that when the pH 7,2-7,3 does not fully dissolve the precipitate obtained in which the process of production of our vaccine product (the process is not complete).

If the pH value to 7.2-7.3 is the solution to leave only the dissolved protein or to raise the pH to 7.5, and 9.0, followed by a decline to baseline, in any case, over time, storing in destabilization of the protein precipitate and fall out. It was determined that the sediment at this stage leads to the decrease of the output of exotoxin a drug and the subsequent processing of the obtained vaccine to reduce output toxoid and reduced immunogenicity.

It was also found that the introduction of formalin at pH 7,2-7,3 to detoxify our vaccine drug leads to a) an additional destabilization of the protein and precipitation, (b) reducing the yield of the final product and b) reduce the immunogenicity of the vaccine.

According to our research, only at pH 7,5-9,0 occurs: a) the complete dissolution of the precipitate, (b) maximum stabilization of the protein molecules of our vaccines, in) Max. output exotoxin-endotoxin as drug g) maximum output toxoid and d) the most high immunogenicity.

It was also determined that the use of formalin full stabilization of the protein occurs only when the pH value of 7.5-9.0 and reagent 0,4-0,8% of the amount of the solution. Higher values of the reagent to give a decrease in the pH of the solution and do not provide the claimed vaccine.

To remove the OS is enough toxicity shigellezne vaccine preserving immunogenicity was only after: (a) dosed adding formalin, b) values of pH of 7.5-9.0 and in) the number of formalin 0,4-0,8% of the amount of the solution. For example, initially add the number of formalin 0,4-0,8% of the amount of solution and after 2 months (keeping in thermostat at 37° (C) determine the toxicity in mice. If it is high, and the amount of free formaldehyde 0,074% of quantities, the latter is brought to 0,18-0,22% of the number of solution (formalin 0,5-0,6% of solution) and incubated solution at 30-60°to finally put the exotoxin in the toxoid.

Usually, after this procedure, the vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, he is neutralized to the required level while retaining its immunogenicity. Getting drug other aforementioned methods leads to low immunogenicity of the vaccine.

It is known that the properties of any protein, in particular the stability in solution at different pH values, linking with various chemicals and power are determined by the presence and value of certain amino acids and their mutual location. Maximum stability Chiellini of exotoxin and toxoid, as we have determined, there is ri pH 7.5 and 9.0.

Based on the research results, we can only assume that between the processes of detoxification and stabilization protein shigellezne vaccine is competition for formaldehyde molecules, and soon after added to the solution. In the molecule of exotoxin for toxicity meet specific active groups of the protein. Stabilization of the molecules of the exotoxin is due to the fact that a significant portion of the reagent displaces the water from the hydrated membrane protein (according to our research, the most this process in shigellezne vaccine pronounced at pH 7.5 and 9.0) and associated with weak chemical bond (otherwise formalin was not determined). But the strength of this connection is enough to keep the formaldehyde and not to give it to the active groups of the protein that are responsible for toxicity. To begin disposal of the latter without their 100%stabilization does not make sense. The detoxification process occurs in two stages. The first phase of more rapid (a few days) and reversible, the second extended in time and ends up creating a stable methylene bridges. To complete the second stage and need more, after a certain period of time, the addition of formalin. Once bringing the concentration of formalin higher than expected results in uneven RA is its distribution in the vaccine in the detox process and, ultimately, to destabilization of the protein and reduce immunogenicity.

Thus, as follows from the above, only by experiment we found out that to get a fully neutralized highly immunogenic shigellezne vaccine is necessary first to maximally stabilize the protein (pH 7.5 to 9.0, and the number of formalin 0,4-0,8% of the amount of the solution), to carry out detoxification of the vaccine, and then optionally enter formalin, and maintain the drug in 30-60°to finally put the exotoxin in the toxoid.

A comprehensive study of the results of these studies led to the idea to use other substances for detoxification shallenge of exotoxin.

Recent studies conducted have shown that along with the formalin similar results gave benzoic acid and its salts. Add to get the vaccine benzoic acid and its salts in an amount of 0.07 to 4.0% of the amount of solution, or a mixture thereof in an amount of 0.1% to 0.3% and 0.03-2.5% of the amount of the solution, and the mixture of formalin and benzoic acid or its salts in an amount of 0.1% to 0.3% and 0.03 to 2.5% of the number of solution, respectively, maintaining the solution at a temperature of 30-60°C for 2 hours to 60 days resulted in detoxification of the drug. Immunization of animals vaccine preparations, obtained using the receiving benzoic acid and its salts, showed their high immunogenic activity.

Prior to that, benzoic acid and its salts to detoxify microbial toxins and vaccines for medical and veterinary drugs were not used. In principle, these compounds were used in the food industry as a preservative and in medicine as a local antiseptic. In nature, benzoic acid and its salts are contained in cranberries.

The claimed group of inventions merged to form a single inventive concept, which aims to obtain various medicines for the treatment and prevention of diseases of man and animals caused by gram-negative opportunistic and pathogenic microorganisms of the intestinal group and their exotoxins.

The technical result of the claimed group of inventions is getting a vaccine preparation containing Shelley toxoid and corpuscular antigens S.dysenteriae, including components of microbial cells, most related antigenically between different pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and giving when vaccination of humans and animals prophylactic and therapeutic effects against various pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia group; when immunization is Anna vaccine farm animals from their milk, colostrum and serum receipt of immunoglobulin preparations with or antibody-based test activity against a wide range of pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins and with preventive and therapeutic effect against diseases caused by the above-mentioned microorganisms. Immunobiological preparation can be used for the treatment and prevention of a wide range of diseases of internal and external organs of humans and animals caused by various pathogenic and conditionally-pathogenic gram-negative and gram-positive microorganisms and their toxins, viruses, fungi, protozoa, helminths.

Examples

Example No. 1. A method of obtaining a vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins. Grown reactor by way of the cultural weight of R-forms S.dysenteriae on casein broth is treated with chloroform, with the aim of dissolving the cell membrane. Then make centrifugation, select the supernatant, add trichloroacetic acid and bring the pH to 3.6. After that make centrifugation, the precipitate is dissolved in a buffer, to which W ill result the pH of the resulting solution to 8.3. With the aim of obtaining toxoid in the drug add formalin in the amount of 0.5% of the amount of solution when the pH of the vaccine to 8.3 and incubated the resulting solution at a temperature of 37°With thermostat in 1-2 months until complete neutralization of the exotoxin. If toxicity persists, then the vaccine sent for final processing by bringing the concentration of free formaldehyde to 0.18% of the number of solution when the pH of the vaccine solution of 8.3 and keeping thermostat additionally within 1-2 months. When this is received the vaccine contains a protein, 10-15 mg/ml nucleic acid is 0.2 - 0.5 mg/ml lipid - traces. Then make the filling and capping derived vaccine.

After that, the vaccine preparation used for immunization of humans and animals with the aim of immunoprophylaxis and immunotherapy of intestinal infectious diseases caused by gram-negative pathogenic and conditionally pathogenic microorganisms of the intestinal group and their exotoxins, and vaccination of farm animals with the aim of obtaining immune raw materials for the production of immunoglobulin preparations.

Example No. 2. A method of obtaining a vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their Exo what okinami. Grown reactor by way of the cultural weight of R-forms S.dysenteriae on casein broth is treated with chloroform, with the aim of dissolving the cell membrane. This was followed by centrifugation, select the supernatant and bring the pH to 3.2 trichloroacetic acid. Then make centrifugation to obtain a precipitate containing particulate antigens and Shelley exotoxin, dissolve the sediment in the buffer, adjusted the pH of the resulting solution to 8.6. With the aim of obtaining toxoid in the drug add benzoic acid in the amount of 1.0% of the number of solution when the pH of the solution vaccines 8.6 and withstand the resulting solution in a thermostat at a temperature of 37°C for 1-2 months to complete neutralization of the exotoxin. When this is received the vaccine contains a protein, 10-15 mg/ml nucleic acid is 0.2 - 0.5 mg/ml lipid - traces. Then make the filling and capping or filling and lyophilization derived vaccine.

After that, the vaccine preparation used for immunization of humans and animals with the aim of immunoprophylaxis and immunotherapy of intestinal infectious diseases caused by gram-negative pathogenic and conditionally pathogenic microorganisms of the intestinal group and their exotoxins, and vaccination of farm animals with the aim of obtaining immunoglobulin preparation the century

Example No. 3. A method of obtaining a vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins. The vaccine was prepared as in example No. 1. Before packaging the vaccine is subjected to freeze drying to obtain powder.

Example No. 4. The method of obtaining the immunoglobulin preparation. After immunization of farm animals vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins obtained in example No. 1, taking the blood with the purpose of obtaining from serum immunoglobulin preparation.

With the aim of obtaining the drug in the blood serum of cattle was added 1 M acetic acid until the solution pH to 4.3. At a temperature of 22°With intensive stirring, Caprylic acid from the calculation of 3.0 ml per 100 ml of solution. After stopping the addition of a reactant continue stirring for 1-2 hours. Next, perform centrifugation, after which the precipitate is removed and the antibodies remain in the solution, the pH of the solution was adjusted to 7.01 M caustic soda under vigorous stirring and cialiswhat obtained ven the rat against physiological solution of sodium chloride. Obtained in this way immunoglobulin preparation contains a fraction of immunoglobulins G, a and M in the ratio of 45:1:4) or antibody-based test and has activity against a wide range of pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins and due to this has a preventive and curative effect in relation to the listed microorganisms.

Example No. 5. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow
(IgG:IgA:IgM)(50:1:5)- 0.25 g
Vitamin a- 1650 ME
a-Tocopherol acetate (vitamin E)0.005 g
Ascorbic acid (vitamin C)0.05 g
Fructose0.2 g
Technological components
for tabletting
(talc and calcium stearate)to weight pills
0.55 g

The drug gave positive results when tested at 10 dobrovo izah, patients with dysentery.

Immunoglobulin fraction isolated from blood serum of cows immunized with a vaccine for immunization and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, gave a pronounced antitoxic and antibacterial effects. Due to the presence of the drug antitoxic antibodies, treatment with less severe intoxication than with traditional methods of treatment. After the end of treatment there was no disruption of the normal intestinal flora observed in the treatment with antibiotics and chemotherapeutic agents.

The introduction of the tablet with the aim of antioxidant therapy with vitamins a and E reduces the level of peroxide compounds, increasing during the disease, increases the reparative processes in the mucous membrane of the intestine, which has a positive impact on the health and led to more rapid recovery. In addition, vitamin a restores the body activity of vitamin E. Vitamin C is added to increase tissue regeneration and reduce intoxication.

Example No. 6. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow0.1 g
Immunoglobulin fraction
the human serum0.1 g
Bifidobacteria- 0,007 g
Vitamin a- 1650 ME
α-Tocopherol acetate (vitamin E)0.005 g
Ascorbic acid (vitamin C)0.05 g
Pyridoxine hydrochloride (vitamin B6)0.005 g
Potassium dihydrophosphate (KN2PO4)- 0.0052 g
Skimmed milk powder0.2 g
Technological components
for tabletting
(talc and calcium stearate)to the masses tablets
0.55 g

Example No. 7. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.2 g
α-Tocopherol acetate vitamin E) 0.01 g
Vitamin a- 1650 ME
Bifidobacteria0.1 g
Lactobacillus0.1 g
Fructose0.05 g
Technological components
for tablettingto the masses tablets
0.55 g

The drug gave positive results when tested at 12 volunteers, patients with dysentery and coli-infection.

Immunoglobulin fraction of colostrum of cows vaccinated with a vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, gave a pronounced antitoxic and antibacterial effect. Due to the presence of the drug antitoxic antibodies, treatment with less severe intoxication than with traditional methods of treatment. Moreover, the increase in dose resulted in a more rapid disappearance of General toxic symptoms, intestinal disorders and bacteriological rehabilitation. After the end of treatment there was no disruption of the normal intestinal flora observed in the treatment with antibiotics and chemotherapeutic agents.

Introduction the inof the tablets of bifidobacteria and lactobacilli led to a more rapid normalization normoflora intestine, than with traditional methods of treatment. Antioxidant therapy with vitamins a and E, known to reduce the level of peroxide compounds, increasing during the disease, increases the reparative processes in the mucous membrane of the intestine, which has a positive impact on the health of patients and led to more rapid recovery.

Example No. 8. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction,
derived from the colostrum of cows,
immunized vaccine
for immunoprophylaxis and immunotherapy
diseases of humans and animals,
caused by pathogenic and conditionally
pathogenic gram-negative
microorganisms of the intestinal group and
their exotoxins0.2 g
Immunoglobulin G cow
protiwaritmicescoy activity0.2 g
α-Tocopherol acetate (vitamin E) 0.01 g
Vitamin a- 1650 ME
Lactoferrin0.1 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 9. Immunobiological preparation in tablet form. To obtain immunobiologics drug use the following components:

Immunoglobulin fraction
serum cow0.4 g
Lactoperoxidase0.05 g
Lactoferrin0.05 g
Bifidobacteria- 0,02 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 10. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

td align="right"> 0.1 g
Immunoglobulin fraction
the milk of a cow0.4 g
Yeast
Technological components
for tablettingto weight pills
0.55 g

Example No. 11. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum goats0.4 g
Lactoperoxidase0.05 g
Lysozyme0.05 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 12. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum sheep0.4 g
Baker's yeast0.05 g
The activated carbon- 0.07 g
Technological components
for tabletas is of to weight pills
0.55 g

Example No. 13. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum sheep0.4 g
Activated carbon0.1 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 14. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow0.4 g
Orosomucoid0.05 g
Fructose0.05 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 15. Immunobiological preparation in tablature the Anna form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum goats0.4 g
The haptoglobin0.1 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 16. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.4 g
Tetracycline hydrochloride0.1 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 17. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 0.25 g
Sulfadimezin- 0.25 g
Technological components
for tablettingto weight pills
0.55 g

Example 18. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow0.4 g
Chloramphenicol0.05 g
Nystatin0.05 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 19. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow0.4 g
Cycloserine0.1 g
Technological components
d is I tabletting to weight pills
0.55 g

Example No. 20. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum sheep- 0,48 g
Furazolidone- 0,02 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 21. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum sheep0.4 g
Ribamidil0.1 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 22. Immunobiological preparation in tablet form. To obtain biologic drug used in the coziness of the following components:

Immunoglobulin fraction
colostrum cow0.4 g
Calcium lactate0.1 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 23. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow0.2 g
Immunoglobulin G man0.2 g
Methylmethanesulfonate chloride- 0,02 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 24. Vaccine formulation in tablet form. To obtain the vaccine preparation to use the following components:

Vaccine for immunization
and imunotherapy disease is s
human and animal
caused by pathogenic and conditionally pathogenic
gram-negative microorganisms
intestinal group and their exotoxins- 0.45 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 25. Multicomponent vaccine formulation in tablet form. To obtain a multicomponent vaccine preparation to use the following components:

Vaccine for immunization
and immunotherapy of diseases
humans and animals caused
pathogenic and conditionally pathogenic
gram
microorganisms Escherichia
groups and their exotoxins0.2 g
The rotavirus vaccine- 0.25 g
Technological components
for t is latinoware to weight pills
0.55 g

Example No. 26. Multicomponent vaccine formulation in tablet form. To obtain a multicomponent vaccine preparation to use the following components:

Vaccine for immunization
and immunotherapy of diseases
humans and animals caused
pathogenic and conditionally pathogenic
gram-negative microorganisms
intestinal group and their exotoxins- 0.45 g
Vi-antigen bruchnotifosny0.05 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 27. Immunobiological preparation in tablet form. To obtain immunobiologics drug use the following components:

Immunoglobulin fraction
colostrum cow- 0.5 g
Methylmethane Ultonia chloride 0.01 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 28. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow0.4 g
Peppermint0.1 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 29. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.2 g
Immunoglobulin G serum
blood sheep0.2 g
Mushroom tea0.1 g
Technological components
the La tabletting to weight pills
0.55 g

Example No. 30. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow0.4 g
Pantocrine0.1 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 31. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 0.25 g
Immunoglobulin a person0.2 g
Arachidonic acid- 0,025 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 32. Immunobiological preparation in tab is tirovannoj form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 0.5 g
Lipoic acid0.005 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 33. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 0.5 g
Arginine0.005 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 34 Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
Siva ODI blood of the cow - 0.5 g
Caffeine0.01 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 35. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 0.45 g
Panasonic0.05 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 36. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 0.45 g
Griseofulvin0.05 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 37. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow- 0.45 g
Clotrimazole0.05 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 38. Immunobiological preparation in tablet form. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.3 g
Methyluracil0.2 g
Technological components
for tablettingto weight pills
0.55 g

Example No. 39. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.1 g
Lactobacillus- 106SOME
α-Tocopherol acetat (vitamin E)0.01 g

The basis for suppository (emulsifier T-2,

fat for chocolate, paraffin)to the masses
the suppository 1.4 g

The drug gave positive results in the treatment of vaginal infections caused by gram-negative pathogenic enterobacteria.

Immunoglobulin fraction of colostrum of cows vaccinated with a vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, gave a pronounced sanitizing effect. Moreover, in contrast to traditional methods of treatment by antibiotics and chemotherapy products of destruction of microorganisms minimally enter the bloodstream and quickly disappears irritation.

Lactobacilli and vitamin E contributed to a more rapid reparative processes of the mucous and restoration of the internal environment of the vagina.

Example No. 40. Immunobiological product in the form of su who pository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow0.05 g
Fraction of immunoglobulins
the human serum0.05 g
α-Tocopherol acetate (vitamin E)0.01 g
Chloramphenicol- 0,02 g
The basis for suppositoryto the masses
(cocoa butter, gelatin weight)the suppository 1.4 g

Example No. 41. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.1 g
Immunoglobulin G man0.05 g
Extract of chamomile flowers- 0,02 g
The basis for suppositoryto the masses
(cocoa butter, lanolin)the suppository 1.4 g

The drug gave positive results in the treatment of vaginal infects and, caused by gram-positive bacteria, gram-negative enterobacteria and mixed infection.

Immunoglobulin fraction of colostrum of cows immunized with a vaccine for immunization and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, and human IgG isolated from the serum or waste of gamma globulin production, gave a good sanitizing effect.

Extract of chamomile has anti-inflammatory and antiseptic properties, weakens allergic reactions, strengthens regeneration of the mucous.

Example No. 42. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow0.15 g
Furazolidone- 0,02 g
The basis for suppositoryto the masses
(butyral)the suppository 1.4 g

Example No. 43. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following component is s:

Immunoglobulin fraction
serum cow- 0.18 g
Fructose0.01 g
Extract herb0.01 g

The basis for suppository

(gelatin, glycerin, water)to the masses
the suppository 1.4 g

Example No. 44. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
milk obtained from cows
immunized vaccine
for immunoprophylaxis and immunotherapy
diseases of humans and animals,
caused by pathogenic and
opportunistic gram-negative
microorganisms of the intestinal group
and their exotoxins0.1 g
Immunoglobu is in G man
with protiwaritmicescoy activity0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 45. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 0.18 g
Lactoperoxidase- 0,02 g
The basis of the suppositoryto the weight of the suppository
1.4 g

Example No. 46. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 0.18 g
Yeast- 0,02 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 47. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation COI is lsout the following components:

Immunoglobulin fraction
colostrum cow- of 0.085 g
Fraction of immunoglobulins
colostrum goats- 0 085 g
Methylmethanesulfonate chloride0.01 g
Orosomucoid- 0,02 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 48. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 0.17 g
Interferon man- 0.03 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 49. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow 0.15 g
Kombucha tea0.05 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 50. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum bull0.15 g
Skim milk powder man0.05 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 51. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow0.05 g
Fraction of immunoglobulins
serum pig0.05 g
Royal jelly0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 52. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.05 g
Immunoglobulin G milk goats0.05 g
Activated carbon0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 53. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction

colostrum goats0.1 g
Chloramphenicol0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 54. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 0,15g
Norsulfazol0.05 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 55. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.15 g
Hlorhinaldon0.05 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 56. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
milk goats0.1 g
Chlorophyllipt0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 57. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.1 g
Ethionamide0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 58. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.15 g
Ganciclovir- 0.03 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 59. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cowto 0.19 g
Opinon0.01 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 60. Immunobiological product in the form of suppose the thorium. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow0.1 g
Iron ferrous lactate0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 61. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow0.15 g
Fructose0.05 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 62. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
milk cows0.15 g
Peanut butter0.05 g
The basis of suppo is a story to the masses
the suppository 1.4 g

Example No. 63. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 0.09 g
Immunoglobulin G deer- 0.09 g
Arginine- 0,02 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 64. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum sheep0.15 g
Lipoic acid (sodium salt)0.05 g
The basis for suppositoryto the masses
the suppository 1.4 g

Example No. 65. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulins what I faction

serum bull0.15 g
Caffeine0.05 g
The basis for suppositoryto the masses
the suppository 1.4 g

Example No. 66. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum goat0.15 g
Panasonic0.05 g
The basis for suppositoryto the masses
the suppository 1.4 g

Example No. 67. Vaccine preparation in the form of suppository. To obtain the vaccine preparation to use the following components:

Vaccine for immunization
and immunotherapy of human diseases
and animals caused
pathogenic and conditionally pathogenic
gram-negative microorganisms
kiseon the th group
and their exotoxins0.2 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 68. Multicomponent vaccine preparation in the form of suppository. To obtain a multicomponent vaccine preparation to use the following components:

Vaccine for immunization
and immunotherapy of human diseases
and animals caused by pathogenic
and conditionally-pathogenic gram-negative
microorganisms
intestinal group and their exotoxins0.1 g
The rotavirus vaccine0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 69. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow 0.15 g
Griseofulvin0.05 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 70. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow0.15 g
Clotrimazole0.05 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 71. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum bull0.1 g
Eagleman0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 72. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction the milk of a cow0.1 gAntinodes0.1 gThe basis of the suppositoryto the masses the suppository 1.4 g

Example No. 73. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow0.1 g
Volekam0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 74. Immunobiological preparation in the form of suppository. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow0.1 g
Methyluracil0.1 g
The basis of the suppositoryto the masses
the suppository 1.4 g

Example No. 75. Immunobiological preparation in the form of ointments. To receive immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Immunoglobulin fraction
serum sheep- 5.0 g
Oil-fatty base
(emulsifier T-2, creamy- 90.0 g
oil, solvent)

Example No. 76. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow- 5.0 g
Immunoglobulin fraction
the human serum- 5.0 g
Oil-fatty base- 90.0 g
(vaseline, vaseline oil)

Example No. 77. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
m is Loka cow - 5.0 g
Immunoglobulin G man- 5.0 g
Oil-fatty base
(lanolin, vaseline, water)- 90.0 g

Example No. 78. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 15.0 g
Oil-fatty base- 85,0 g
(vaseline, starch)

Example No. 79. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Lactoferrin- 5.0 g
Oil-fatty base- 90.0 g
(vaseline, water)

The drug gave positive results in the healing of wounds of different origin.

Immunoglobulin fraction obtained from the colostrum of cows immunized with a vaccine for immunoprophylactic the key and immunotherapy of human and animal diseases, caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, contains antibodies to the exotoxins and corpuscular antigens of gram-negative microorganisms, as well as a significant range of natural antibodies to gram-positive microorganisms.

Lactoferrin has a strong bacteriostatic action.

Example No. 80. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Lysozyme- 5.0 g
Oil-fatty base- 90.0 g
(butter, jelly,
paraffin, water)

Example No. 81. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow- 9.0 g
Bifidobacteria- 107SOME
Oil-the fat of the Nova - 90.0 g

Example No. 82. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
milk goats- 5.0 g
Yeast- 5.0 g
Oil-fatty base- 90.0 g

Example No. 83. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum sheep- 5.0 g
Vitamin a- 1.0 g
α-Tocopherol acetate- 2.0 g
Riboflavin (vitamin B2)- 2.0 g
Oil-fatty base- 90.0 g

Example No. 84. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

td align="left"> Methylmethanesulfonate chloride
Immunoglobulin fraction
serum cow- 5.0 g
- 5.0 g
Oil-fatty base- 90.0 g

Example No. 85. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow- 5.0 g
Orosomucoid- 5.0 g
Oil-fatty base
(butter, jelly,
paraffin, water)- 90.0 g

The drug gave positive results in the treatment of various wounds, wound infections and burns.

Immunoglobulin fraction obtained from the blood serum of cows immunized with a vaccine for immunization and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, contains antibodies to the exotoxins of gram-negative microorganisms, as well as a significant range of natural antibodies to gram-positive microorganisms.

Orosomucoid has a strong healing effect.

Example No. 86. Immunobiologics is the first drug in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 5.0 g
Interferon man
leukocyte- 5 million ME
Oil-fatty base- 90.0 g

Example No. 87. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Aloe Vera- 5.0 g
Oil-fatty base- 90.0 g

Example No. 88. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Laminaria extract diabetes- 5.0 g
Oil-fatty base- 90.0 g

Example No. 89. Immunobiologic the ski in the preparation of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Extract milk salmon- 5.0 g
Oil-fatty base- 90.0 g

Example No. 90. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Propolis- 5.0 g
Oil-fatty base- 90.0 g

Example No. 91. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum bull- 5.0 g
Chloramphenicol- 5.0 g
Oil-fatty base- 90.0 g

Example No. 92. Immunobiological preparation in the form of ointments. To obtain immunobiologics is on drug use the following components:

Immunoglobulin fraction
serum cow- 5.0 g
Streptocide- 5.0 g
Oil-fatty base- 90.0 g

Example No. 93. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 5.0 g
Nitroxoline- 5.0 g
Oil-fatty base- 90.0 g

Example No. 94. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Sodium UniNet- 5.0 g
Oil-fatty base- 90.0 g

Example No. 95. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 3.0 g
Streptomycin sulfate- 5.0 g
Oil-fatty base- 90.0 g

Example No. 96. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow- 5.0 g
Acyclovir- 5.0 g
Oil-fatty base- 90.0 g

Example No. 97. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Griseofulvin- 5.0 g
Oil-fatty base- 90.0 g

Example No. 98. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fra is tion
the milk of a cow- 5.0 g
Clotrimazole- 5.0 g
Oil-fatty base- 90.0 g

Example No. 99. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 3.0 g
Opinon- 5.0 g
Oil-fatty base- 90.0 g

Example No. 100. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Calcium lactate- 5.0 g
Oil-fatty base- 90.0 g

Sample No. 101. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow - 5.0 g
Pectin- 5.0 g
Oil-fatty base- 90.0 g

Example No. 102. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow- 5.0 g
Sea buckthorn oil- 10,0 g
Oil-fatty base- 85,0 g

Example No. 103. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 5.0 g
Arginine- 5.0 g
Oil-fatty base- 90.0 g

Example No. 104. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

- 5.0 g
Immunoglobulin fraction
serum bull- 5.0 g
Lipoic acid
Oil-fatty base- 90.0 g

Example No. 105. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 5.0 g
Viburnum- 5.0 g
Oil-fatty base- 90.0 g

Example No. 106. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Eleutheroside- 5.0 g
Oil-fatty base- 90.0 g

Example No. 107. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
colostrum cow- 5.0 g
Eagleman- 5.0 g
Oil-fatty base - 90.0 g

Example No. 108. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
serum cow- 5.0 g
Antinodes- 5.0 g
Oil-fatty base- 90.0 g

Example No. 109. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

Immunoglobulin fraction
the milk of a cow- 5.0 g
Volekam- 5.0 g
Oil-fatty base- 90.0 g

Example No. 110. Vaccine preparation in the form of ointments. To obtain the vaccine preparation to use the following components:

Vaccine for immunization
and immunotherapy of diseases
humans and animals caused
pathogenic and conditionally pathogenic
g is americateledyne microorganisms
intestinal group and their exotoxins- 10,0 g
Oil-fatty base- 90.0 g

Example No. 111. Multicomponent vaccine preparation in the form of ointments. To obtain a multicomponent vaccine preparation to use the following components:

Vaccine for immunization
and immunotherapy of diseases
human and animal
caused by pathogenic and
opportunistic
gram-negative microorganisms
intestinal group and their exotoxins- 5.0 g
Staphylococcal vaccine- 3.0 g
Oil-fatty base- 90.0 g

Example No. 112. Immunobiological preparation in the form of ointments. To obtain immunobiological preparation use the following components:

/tr>
Immunoglobulin fraction
serum cow- 5.0 g
Methyluracil- 5.0 g
Oil-fatty base- 90.0 g

Vaccine formulation, obtained from strains of R-form and S.dysenteriae includes Shelley toxoid and particulate antigens, has high immunogenicity. Due to the presence in the vaccine antigens common to gram-negative microorganisms, when the immunization of animals produced a wide range of antibodies to pathogenic microorganisms and their exotoxins, which is confirmed by in vitro and in vivo. Shows the inefficiency of commercial immune immunoglobulin preparations - lactoglobulin protivoallergennogo and against pathogenic bacteria and Salmonella against Shigella and shallenge of exotoxin, and the ability to use data lactoglobulin drug instead of the placebo in the study of in vivo antibacterial and antitoxic activity protivoglistnyh immunoglobulin preparations.

It is proposed to use this vaccine formulation for the prevention of diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms, primarily intestinal group, as well as to obtain immunoglobulin drugs with a broad spectrum antibacterial and antitoxic activity of colostrum, milk and blood immune animals.

Describes an original method of neutralization is olavarrieta shigellezne vaccine consisting of exotoxin and corpuscular antigens, with the purpose of receiving the vaccine preparation using benzoic acid and its salts, and also together with formalin.

Variants of immunobiological products in a joint komponovanie this vaccine with other vaccines and immunoglobulins and immunoglobulin preparations with various biologically active substances and drugs of animal, vegetable and synthetic origin.

The claimed group of inventions combined to form a single inventive concept, which is aimed at immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins.

1. A method of obtaining a vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, characterized in that it provides for the cultivation of strains R-forms S.dysenteriae, lysis of the cells by treatment with chloroform, centrifugation to obtain a supernatant, and then the supernatant is treated with the utmost monobasic carboxylic acids or their derivatives to a pH of 3.0 to 5.0, zentrifugenbau is their obtaining a precipitate, containing particulate antigens and Shelley exotoxin, dissolving the precipitate in a buffer and bringing the pH to 7.5, and 9.0, adding formalin in an amount of 0.4-0.8% of the amount of solution, or benzoic acid, or its salts in an amount of 0.07 to 4.0% of the amount of solution or their mixture, and the amount of formalin is 0.1-0.3% of the amount of solution amount of benzoic acid or its salts of 0.03 to 2.5% of the amount of the solution, maintaining the solution at a temperature of 30-60°C for 2 h to 60 days before the transfer of exotoxin in the toxoid with receipt of the vaccine, followed by filling and corking.

2. The method according to claim 1, characterized in that prior to packaging the final product is subjected to freeze drying to obtain granules or powders.

3. The method according to claim 1, characterized in that before filling in the vaccine injected ointment base or basis for suppository.

4. A method of obtaining a vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, characterized in that it provides for the cultivation of strains R-forms S.dysenteriae, lysis of the cells by treatment with chloroform, centrifugation to obtain a supernatant, and then the supernatant is treated with the utmost monobasic carboxylic sour the AMI or their derivatives to a pH of 3.0 to 5.0, centrifugation to obtain a precipitate containing particulate antigens and Shelley exotoxin, dissolving the precipitate in a buffer and bringing the pH to 7.5, and 9.0, adding formalin in an amount of 0.4-0.8% of the quantity of solution or benzoic acid, or its salts in an amount of 0.07 to 4.0% of the amount of solution or their mixture, and the amount of formalin is 0.1-0.3% of the amount of the solution, and the amount of benzoic acid or its salts of 0.03 to 2.5% of the amount of the solution, maintaining the solution at a temperature of 30-60°C for 2 h 60 days, followed by additional processing of formalin to the content of free formaldehyde in the solution 0,18-0,25% of the amount of solution, or benzoic acid, or its salts or mixtures thereof, until the content of free benzoic acid or salts of benzoic acid in a solution of 0.07 to 4.0% of the amount of the solution, and the amount of free formaldehyde in the solution is 0,037-0.12% of the amount of the solution, and the amount of free benzoic acid or its salts in a solution of 0.03 to 2.5% of the amount of the solution, keeping in 30-60°C for 2 h 30 days before the transfer of exotoxin in the toxoid with receipt of the vaccine, followed by filling and corking.

5. The method according to claim 4, characterized in that before filling in the vaccine injected ointment base or basis for suppository.

6. The method according to claim 4, different is the present, before packaging the final product is subjected to freeze drying to obtain granules or powders.

7. Vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, characterized by the fact that obtained by the method according to any one of claims 1 to 6.

8. The method of obtaining the immunoglobulin preparation for the prevention and treatment of diseases of man and animals caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, characterized in that it provides for the immunization of animals with the vaccine for immunoprophylaxis and immunotherapy of human and animal diseases caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, obtained by the method according to any one of claims 1 to 6, the fence in animals immune milk and/or colostrum, and/or blood, obtaining immunoglobulin fraction, sterilization, filling and capping.

9. The method of obtaining the immunoglobulin preparation of claim 8, characterized in that after sterilization are drying.

10. Immunoglobulin preparation for prophylaxis and treatment of diseases of man and animals caused by pathogenic and conditionally-PA is ogenyi gram-negative microorganisms Escherichia groups and their exotoxins, characterized by the fact that obtained by the method according to any of PP-9.

11. Immunoglobulin preparation of claim 10, characterized in that additionally at least contains one component selected from the range of: flavorings, aromatic additives, base for suppositories, the basis for ointment forms, processing additives for tableting.

12. Immunobiological preparation for prophylaxis and treatment of diseases of man and animals caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and exotoxins, characterized in that it contains immunoglobulin preparation obtained by the method of claim 8, and at least two components, selected from the range: lactoferrin, enzymes, inhibitors of proteolytic enzymes, drugs normoflora humans and/or animals, yeast, vitamins, vitamin-like substances, proteins of the acute phase of human and/or animal cytokines by human and/or animal components of higher plants, components of lower plants, components of natural products origin, bee products, chelators, antibiotics, antimicrobial drugs, sulfa drugs, antimicrobial and antiparasitic drugs of natural origin, anti-TB drugs, antiviral drugs, protivogribkovi the antibiotics, synthetic antifungal drugs, stimulants metabolic processes, antioxidants, mineral supplements, carbohydrates, lipids, interchangeable and/or essential amino acids, organic acids, alkaloids, glycosides, flavorings, aromatic additives, base for suppositories, the basis for ointment forms, processing additives for tableting.

13. Multicomponent vaccine for prophylaxis and treatment of diseases of man and animals caused by pathogenic and conditionally-pathogenic gram-negative microorganisms Escherichia groups and their exotoxins, characterized in that it contains at least one component of the vaccine, obtained by the method according to any one of claims 1 to 6.



 

Same patents:
Antibacterial agent // 2262346

FIELD: biotechnology, microbiology.

SUBSTANCE: invention proposes applying Flavobacterium odoratum culture as an antibacterial agent isolated from drinking mineral water "Ust-Kachkinskaya" from the hole 1/99. Microorganism Flavobacterium odoratum inhibits growth of Staphylococcus aureus, colon bacillus and yeast-like fungi Candida albicans that allows using microorganism Flavobacterium odoratum as an antibacterial agent. Invention can be used as an antibacterial agent.

EFFECT: valuable medicinal properties of agent.

2 ex

FIELD: biotechnology, medicine, antibiotics.

SUBSTANCE: invention proposes to the new compound amycomycin of the molecular formula C65H115NO18 (structural formula is given on the invention claim) that shows an antibacterial activity. Amycomycin, its pharmaceutically acceptable salts and derivatives in all their stereoisomeris and tautomeric forms can be obtained by culturing microorganism Amycolatopsis sp. ST 101170 (DSM 12216) under aerobic conditions on the nutrient medium containing the necessary nutrient components. The end product is isolated and purified and converted if necessary to its pharmacologically acceptable salt, ester, ether and other chemical derivatives and eliciting the same spectrum of antibacterial activity. Amycomycin is a component of the pharmaceutical composition eliciting an antibacterial activity. Amycomycin acts as an antibiotic. Invention provides inhibition of microorganisms with resistance to vancomycin and teicoplanin used in treatment of infections caused by Staphylococcus aureus.

EFFECT: improved preparing method, valuable medicinal properties of amycomycin.

7 cl, 2 tbl, 4 ex

FIELD: biochemistry, medicine.

SUBSTANCE: invention relates to two forms of peptide isolated from annelid worm (Arenicola marina) eliciting the broad spectrum of antibacterial effect. Indicated forms differ by a single amino acid residue at position 10 wherein at position 10 arenicin-1 has Val and arenicin-2 has Ile. Invention provides expanding assortment of antibacterial agents.

EFFECT: valuable medicinal properties of peptides.

1 tbl, 3 dwg, 4 ex

FIELD: medicine, gynecology, pharmacy.

SUBSTANCE: invention proposes using pimafucin (natamycin) as agent for treatment of bacterial vaginitis. Method for treatment of bacterial vaginitis involves intravaginal administration of pimafucin as 2% cream, 2 times per a day in morning and evening for 7-10 days and for first 3 days pimafucin-containing vaginal suppository in the dose 100 mg is administrated additionally in evening after administration of cream into vagina. Invention provides high effectiveness of treatment and clinical-etiological recovery in 92.3% of cases being without prescription of medicinal preparations. Method has no contraindications and can be used in all period of pregnancy and without adverse effects.

EFFECT: improved treatment method, enhanced effectiveness of agent and treatment.

2 cl, 1 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to new substituted 7-sulfonyl-benzo[b][1,4]diazepines of the general formula (1) , their pharmaceutically acceptable salts, N-oxides or hydrates that elicit properties of a protein kinase inhibitor that can be used in pharmaceutical industry. In compounds of the general formula (1) R1 and R2 represent independently of one another hydrogen atom, inert substitute, optionally substituted carboxymethyl group, optionally substituted carbamoylmethyl group; R3 and R4 represent independently of one another hydrogen atom or inert substituted, or R3 and R4 in common with carbon atom to which they are bound form optionally substituted (C3-C7)-cycloalkyl, optionally substituted (C4-C7)-heterocyclyl or optionally substituted ethylene group; R5 represents optionally substituted amino-group or optionally substituted azaheterocyclyl. Also, invention relates to sulfochlorides of the general formula (2) that are used for preparing compound of the formula (1), and to methods for preparing compounds of general formulae (1) and (2). Also, invention relates to a pharmaceutical composition in form of tablets, capsules or injection formulations placed into pharmaceutically acceptable package, and to the focused library for the search of biologically active compound-leaders.

EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds.

7 cl, 2 sch, 1 tbl, 3 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to an aqueous composition consisting of moxifloxacin hydrochloride and sodium chloride and comprising from 0.04% to 0.4% (mas/vol) (as measured for the amount of moxifloxacin) of moxifloxacin hydrochloride and from 0.4% to 0.9% (mas/vol) of sodium chloride. Also, invention relates to applying this composition with the aim for preparing a medicinal agent used for prophylaxis or treatment of bacterial infections in humans or animals. Invention provides stability of the prepared moxifloxacin solution as moxifloxacin hydrochloride in the presence of iron ions.

EFFECT: improved properties of compositions.

6 cl.

FIELD: antibiotics, chemical technology.

SUBSTANCE: crystallization of azithromycin dihydrate is carried out by alkalization of an aqueous-organic azithromycin salt with the ratio water/solvent = from 1:1 to 3;1 and up to pH value 8-10. Methanol, ethanol, isopropanol, acetonitrile or dioxane can be used as a solvent. Method provides enhancing stability and homogeneity of the end crystalline product.

EFFECT: improved crystallizing method.

1 dwg, 3 ex

FIELD: medicine, veterinary science.

SUBSTANCE: a new group of compounds, such as: 1) 1.3-benzodixole-5-β-nitroethylene

, 2) 1.3-benzodioxole-5-β-nitropropylene

, 3)benzimidazole-5-β-nitropropylene

, 4) 2-methylbenzimidazole-5-β-nitroethylene

, 5) benzoxazole-5-β-nitroethylene

, 6) 2-methylbenzoxazole-5-β-nitropropylene

has been suggested to protect against the agents of bacterial, protozoan and fungoid nature. Compounds are being the derivatives of heteronitroalkenes (dioxoles, oxazoles, imidazoles) with below-mentioned structural formulas being efficient to gram-positive bacteria and gram-negative aerobes, fungi of Candida, Trichophyton and other types, trichomonads. They could be applied at treating wound infections, fungoid lesions, septic states, pneumonia, trachoma, ornithosis, salmonellosis.

EFFECT: higher efficiency of protection.

5 cl, 5 tbl

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to new 5-aryl-1-phenyl-4-heteroyl-3-hydroxy-3-pyrroline-2-ones of the formula:

wherein (1) X means sulfur atom (S); R means (CH3)2CH; (2) X means sulfur atom (S); R means (CH3)3C; (3) X means oxygen atom (O); R means (CH3)3C. Compounds of the formula (I) are prepared by interaction of the corresponding heteroylpyruvic acid methyl ester with mixture of aniline and aromatic aldehyde in acetic acid medium at short-time heating. Compounds elicit an anti-bacterial activity with value MIC = 3.9-7.8 mcg/ml as compared with 62-1000 mcg/ml for analogue.

EFFECT: valuable properties of compounds.

1 tbl, 3 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes a method for preparing derivatives of benzoxazine and describes a method for preparing compound represented by the formula . Method involves of compound represented by the formula (I): with compound represented by the formula (II-1-a): in the presence of a base to form compound represented by the formula (III-1-a): followed by reduction of this compound to compound represented by the formula (IV-a): , interaction of this compound with compound represented by the following formula: to form compound represented by the formula (V-a): and the following treatment of this compound in the presence of a base to obtain compound represented by the formula (VI-a): , treatment of this compound with compound of boron trifluorine and its conversion by this manner to the boron chelate compound represented by the following formula: followed by reaction of this compound with 4-methylpiperazine to obtain compound represented by the following formula: followed by cleavage and elimination of boron chelate of this compound. In each of above given formulas X1, X2 and X3 represents independently halogen atom; R1 represents a leaving group; R3 represents hydrogen atom or carboxyl-protecting group; R4 represents hydroxyl-protecting group; each R5 and R6 represents independently alkyl group comprising 1-6 carbon atoms; R7 represents carboxyl-protecting group; Y represents alkoxy-group comprising 1-6 carbon atoms, halogen atom or dialkylamino-group (wherein alkyl groups can be similar or different and each represents alkyl group comprising 1-6 carbon atoms). Also, invention describes variants above described method, methods for preparing intermediate compounds and intermediate compound. Invention provides industrially favorable methods for preparing intermediate compounds that are useful for preparing compounds with antibacterial properties.

EFFECT: improved preparing methods, valuable properties of compounds.

96 cl, 102 ex

FIELD: medicine microbiology.

SUBSTANCE: claimed method includes administering before contamination to the animal subsequently in right pope then after 14 days in left pope 0.2 ml of non-complete Freund's adjuvant with equal volume of physiological salt solution. Subsequent administering after 14 days in right pope up to 10 LD50 of Bacillus anthracis 81/1 spore dredge doesn't cause animal death for long period (monitoring time is 35 days).

EFFECT: immune serum for screening of anthrax diagnosis preparation.

1 dwg, 1 tbl, 8 ex

The invention relates to biotechnology and can be used for the treatment and prevention of disease associated with infection by Streptococcus or G+ bacteria
The invention relates to the medical industry and relates to a method of producing drug for active immunization against tularemia

The invention relates to medicine and relates to humanized antibodies that recognize the verotoxin II, and producing their cell line

The invention relates to medicine, infectious diseases and can be used for integrated prevention of anthrax

The invention relates to bacteriophages for use in the treatment or prevention of bacterial infections, particularly bacterial infections of the mucous membranes

The invention relates to the field of biotechnology and immunology, and can be used to stabilize the physicochemical and biologic properties globulin protivovirusnogo

The invention relates to medicine, infectious diseases and can be used for the treatment of generalized forms of anthrax infection

The invention relates to the field of medicine, Microbiology and immunology

FIELD: veterinary science.

SUBSTANCE: vaccine against porcine salmonellosis contains cell suspension of attenuated vaccine strain Salmonella choleraesuis VGNKI SC 230-DEP in the following ratio of components, vol.-%: suspension of strain Salmonella choleraesuis VGNKI SC 230-DEP with concentration 100-120 billion cells in cm3, 42.0-55.0; sucrose, 5.0-7.5; gelatin, 1.5-2.0, and distilled water, the balance. Morbidity of piglets immunized with vaccine is reduced 2-fold and their safety is by 8.6% higher as compared with the same indices for piglets immunized with the known vaccine from the strain Salmonella choleraesuis VGNKI № 9. Vaccine shows enhanced economy in producing and exhibits stable genetic markers.

EFFECT: improved, enhanced and valuable properties of vaccine.

5 tbl, 8 ex

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