Composition containing bacterial waste products useful for human body

FIELD: biotechnology.

SUBSTANCE: invention is a composition having antibacterial, immunostimulating, anti-allergic and anti-inflammatory action, containing bacterial waste products useful for human body, in the form of exometabolites and fermentolysis products, characterised in that it is a culture medium of lactic acid bacteria, containing laxarane in an amount of 5-10 g/ml, caseicyne, isracydine or their mixture and lectins in an amount of 0.05-2.5 mol/l, histamine in an amount of 0.8-2.0 mmol/l and monocarboxylic fatty acid with an unbranched chain, namely, acetic acid, propionic acid, butyric acid and valeric acid - in an amount of 10-20 mg/ml.

EFFECT: expanding the range of agents having complementary antibacterial, immunomodulating, anti-allergic and anti-inflammatory action.

4 cl, 5 ex

 

The invention relates to the biotechnology and pharmaceutical industries and is intended for use in the production and application of medical immunobiological preparations and biologically active additives to food.

It is now established that the use of live probiotic microorganisms may in some cases lead to problems microecology and the emergence of human diseases (Shenderov B. A. Medical microbial ecology and functional nutrition. Volume III. Probiotics and functional food. - M: Grant, 2001. - S. 217-224).

So promising is the development of products based on metabolites of probiotic microorganisms (EN 2397246, C12N 1/20, A23L 1/054).

Known bacteriocins of lactic acid bacteria, which are proposed as biocides for industrial use in biocidal compositions (WO 2012145185, A01N 63/02). According to this invention bacteriocins produced by strains of lactic acid bacteria selected from the group of: Streptococcus spp., Lactococcus spp., Lactobacillus spp., Pediococcus spp., Leuconostoc spp., Bifidobacterium spp. and Enterococcus spp. Bacteriocins selected from the group of: acidophilus, grocin, alveicin, aureocin, bulgarican, carnosin, casticin, colicin, curvaticin, diplococcin, divercin, enterocin, enteroclysis, epidermin, erwiniocin, glycinecin, halocin, helveticin, lactococci, lacticin, lactocin, leucoccin, mesentericin, lowlands, pediocin, plantaricin, skazi is, subtilin, sulfolobicin, turitzin, trifolitoxin, vibriocin and varnerin. Biocidal composition on the basis of these bacteriocins is designed to handle water supply systems, including treatment system disinfection of drinking water.

Known preservative agricultural products, including antimicrobial agent lowlands, lactic acid, extracellular metabolites of lactic acid bacteria with antimicrobial activity, and intracellular metabolites of lactic acid bacteria obtained by extraction ruined or intact cells of lactic acid bacteria with water or aqueous salt solutions, and as lactic acid bacteria contains strains of lactic acid bacteria with antimicrobial activity (RU 2159553, AV 7/14, AW 7/10, A23L 1/212, A23L 3/3463).

The main disadvantages of these analogues on the basis of bacteriocins of lactic acid bacteria are no combinations of metabolic products of bacteria possessing a complementary antibacterial, immunomodulatory, anti-allergic and anti-inflammatory action, and that they are not intended for use as a medical immunobiological preparations and biologically active additives to food.

Known properties of exopolysaccharides of lactic acid bacteria - lacarno as: stimulation of growth of some is that lactic acid bacteria and suppress the number of enteropathogenic Escherichia coli and Staphylococcus; stimulation of phagocytic activity of macrophages and influence on the production of key proinflammatory cytokines; wound-healing properties. Also known properties lacarno to improve structural-mechanical, physico-chemical, microbiological and sensory properties of salami (Pravdivtseva M. I. Characterization of the biological activity of exopolysaccharides bacteria of the genus Lactobacillus and prospects of their use: author. Diss.... Kida. Biol. Sciences. - Saratov, 2012. - 21 S. - URL: http://www.sgau.ru/assets/files/Nauka/autoref/pravdivceva_mi.doc).

The main disadvantages of this analogy, which describes the properties and possible applications of exopolysaccharides of lactic acid bacteria - lacarno are no combinations of metabolic products of bacteria possessing a complementary antibacterial, immunomodulatory, anti-allergic and anti-inflammatory action, and that is not designed compositions intended for use as a medical immunobiological preparations and biologically active additives to food.

It is known tool for early treatment of radiation and combined radiation-thermal lesions, representing microbial cells and products of their metabolism in the environment of the cultivation, obtained by inactivation of the consortium strains actobacillus acidophilus as, NK1and K3W24taken in the ratio 1:1:1 with 107-108living microbial cells in 1 ml growth medium (RU 2123344, AK 35/74).

Known composition for correction of dysbiosis, based on a consortium of strains of lactobacilli, providing the ratio of the sum of short-chain monocarboxylic fatty acid fraction (2-C4) and isomer butyric acid from 20:1 to 40:1 (EN 2431492, AK 35/74, OR 1/00). The technical result of the claimed invention is the provision of personalized correction of dysbiosis in patients with a high rate of the inverse ratio of the sum of the fractions of short-chain monocarboxylic fatty acids (C4-C6) to the sum of the fractions of their isomers (C4-C6).

The main disadvantage of this analog is no combination of metabolic products of bacteria possessing a complementary antibacterial, immunomodulatory, anti-allergic and anti-inflammatory action.

Known drug hilak Forte, containing short-chain volatile fatty acids, which restores the damaged intestinal infectious diseases of the gastrointestinal tract, stimulating the regeneration of epithelial cells of the intestinal wall, restoring violated the first fluid and electrolyte balance in the gut. Hilak Forte enhances the protective functions of the body through stimulation of the immune response (hilak Forte (Hylak forte): instructions for use, contraindications and composition. - URL: http://www.rlsnet.ru/tn_index_id_3474.htm).

The main disadvantage of these analogues is no combination of metabolic products of bacteria possessing a complementary antibacterial, immunomodulatory, anti-allergic and anti-inflammatory action.

The closest analogue of the claimed invention - a prototype is a comprehensive supplementation of the food product obtained by culturing probiotic microorganisms - representatives of normal microflora of the person, up to a maximum accumulation of biomass, followed by the separation of microorganisms and content of major exometabolites, mg/l: exopolysaccharides 50,0-400,0, organic acids, converted to lactic acid 9,0-12,0, b vitamins 80,0-100,0 (EN 2397246, C12N 1/20, A23L 1/054).

The main disadvantage of the prototype is the lack of combination in the composition of the metabolic products of bacteria possessing a complementary antibacterial, immunomodulatory, anti-allergic and anti-inflammatory action.

The main task of the invention is the combination in the composition of the waste products of bacteria with cooperation is madapollam antibacterial, immunomodulatory, anti-allergic and anti-inflammatory action.

The task is implemented due to the fact that the composition represents the environment of the cultivation of lactic acid bacteria containing lakaran in the amount of 5-10 g/ml, casticin, irazein or their mixture and lectins in the amount of 0.05-2.5 mol/l histamine in the amount of 0.8 to 2.0 mmol/l and monocarboxylic fatty acids with unbranched chain, namely, acetic acid, propionic acid, butyric acid and valeric acid in a dose of 10-20 mg/ml of the Composition may also contain additives target and be made in the form of suspensions or cream, or ointment, or pasta, or masks. The environment of the cultivation of the bacteria may be selected from the range: fermented milk having a fat content of 0.5-1.5% and pH 5.0 to 6.8, fermented milk having a pH of 5.0 to 6.8, fermented skim, evaporated 10-20% milk having a pH of 5.0 to 6.8, the environment on the basis of deoxidized breast means of hydrochloric acid casein whey after culturing bacteria, the environment on the basis of deoxidized breast molochnokislogo casein whey after culturing bacteria, the environment on the basis of deoxidized breast limnocalanus casein whey after culturing bacteria, casein-yeast medium after culturing bacteria, hydrolysate-dairy creapole cultivation of bacteria or their mixtures. As laksamana composition may contain lakaran selected from range: lakaran Z, lakaran 1936, lakaran 1596 or their mixture. As kazicina the composition may contain casticin And casticin or In their mixture. As the target additive composition may contain an infusion of tansy, infusion of sage, a decoction of oak bark, casein, gelatin, agar, glycerol, egg yolk, egg albumen, pectin, cellulose, derivatives of cellulose, bentonite, kaolin, Aerosil, copper sulfate, copper gluconate, chinosol, chitosan, water, licorice extract, rosehip extract, infusion of chamomile, inulin extract, Jerusalem artichoke extract, chicory, infusion of fireweed, the infusion of peppermint, oil from the seeds of milk Thistle, wax emulsion, Combivir, lanolin, spermaceti, vaseline, ceresin, vaseline oil, artificial vaseline, palmitin, hydrogenated fat, preterition fat, confectionery fat, palm olein, palm stearin, olive oil, peach oil, sunflower oil, castor oil, polyethylene oxide, nipagin, nipazol, microcare RM, microcare IT or mixtures thereof.

In the first results of our studies was established provides solution to this problem is a new set of original distinguishing features: has a list of indicators (the composition of the waste products of lactic acid bacteria, actually is which complements and enhances each other), providing a combination of antibacterial, immunomodulatory, anti-allergic and anti-inflammatory action of the composition; designed to be achieved in the process of cultivation and purification of values (the concentration of laksamana, kazicina, aracytine and lectins, histamine and short-chain monocarboxylic fatty acids with unbranched chain), to obtain optimal combination set properties of composition. Was developed in the priority order defined indicators used in the selection of nutrient media, strains of lactic acid bacteria and culturing conditions, providing a solution for the task and represents the following sequence: the concentration of histamine, the concentration of short-chain monocarboxylic fatty acids with unbranched chain and the concentration of laksamana, kazicina, aracytine and lectins.

From the patent and technical literature and practice of production of medical immunobiological preparations and biologically active additives to food is unknown composition containing useful for human body waste products of lactic acid bacteria in the form of exometabolites and products of enzymatic lysis by, which would be identical to declare.

Hence, the legitimate conclusion on the compliance of the claimed solution is s the criterion of "novelty".

The above set of essential features necessary and sufficient for obtaining a technical result - the combination in the composition of the metabolic products of bacteria possessing a complementary antibacterial, immunomodulatory, anti-allergic and anti-inflammatory action, which provides a list of identified parameters (composition of the waste products of bacteria, which complements and enhances each other), resulting in the cultivation and purification of the values of these indicators (concentrations of laksamana, kazicina, aracytine, lectins, histamine and short-chain monocarboxylic fatty acids with unbranched chain), to obtain optimal combination set properties of composition.

Between the existing signs and solve problems there is a causal relationship, where each topic are needed and effect on obtaining a technical result which, together, signs sufficient to obtain it. Legitimate conclusion about conformity of the proposed technical solution the criterion of "inventive step".

The proposed composition with its essential characteristics can be obtained repeatedly, and therefore, the proposed solution meets the criterion of "industrial applicability"./p>

The claimed invention was tested upon receipt of composition and the study of their properties in experimental animal models of diseases. Below are the results of this testing. While examples of the obtained variants of the compositions and their properties show a specific implementation of the invention but do not limit the scope of the claims of the formula of the claimed invention.

Example 1. The resulting composition, which represents the environment of the cultivation of lactic acid bacteria (based environment deoxidized breast limnocalanus casein whey after culturing bacteria) containing bacterial exopolysaccharides (a mixture of laksamana Z laxamana 1936) in an amount of 10 g/ml, antimicrobial peptides (mixture kazicina And kazicina In and irazein) and lectins in the amount of 2.5 mol/l histamine in the amount of 2.0 mmol/l and short-chain monocarboxylic fatty acids with unbranched chain (a mixture of acetic acid, propionic acid, butyric acid and valerianic acid) in the amount of 20 mg/ml

The properties of the composition were investigated in the experimental animal model of eczema, pyoderma complications produced using inbred line BALB/c mice. In the oral administration of the obtained composition and its application to areas of rash on the skin of an experiment is analnyj animals eczematous rashes and symptoms of pyoderma was resolved. Marked the elimination of the pathogen pyoderma - Staphylococcus aureus. Normalized immunological parameters of experimental animals (including the ratio of CD4 - and CD8-cells, as well as the reaction of besttransport lymphocytes). Decreased levels of histamine in the content of the intestine. In the samples of the epidermis and dermis derived from permitted lesions, histological examination revealed no signs of inflammatory reaction. Thus was established the combination of antibacterial, immunomodulatory, anti-allergic and anti-inflammatory actions of the obtained composition.

Example 2. The resulting composition, which represents the environment of the cultivation of lactic acid bacteria (mix medium on the basis deoxidized molochnokislogo casein whey after culturing bacteria and casein-yeast medium after culturing bacteria) containing bacterial exopolysaccharides (laksamana Z) in an amount of 5 g/ml, antimicrobial peptides (mixture kazicina and irazein) and lectins in the amount of 0.05 mol/l histamine in the amount of 0.8 mmol/l and short-chain monocarboxylic fatty acids with unbranched chain (a mixture of acetic acid, propionic acid, butyric acid and valerianic acid) at 10 mg/ml

The properties of the composition were investigated in the experimental LM is now the model eczema, complicated by pyoderma produced using inbred line BALB/c mice. In the oral administration of the obtained composition and its application to areas of rash on the skin of experimental animals eczematous rashes and symptoms of pyoderma was resolved. Marked the elimination of the pathogen pyoderma - Staphylococcus aureus. Normalized immunological parameters of experimental animals (including the ratio of CD4 - and CD8-cells, as well as the reaction of besttransport lymphocytes). Decreased levels of histamine in the content of the intestine. In the samples of the epidermis and dermis derived from permitted lesions, histological examination revealed no signs of inflammatory reaction. Thus was established the combination of antibacterial, immunomodulatory, anti-allergic and anti-inflammatory actions of the obtained composition.

Example 3. The first song that represents the environment of the cultivation of lactic acid bacteria (mix medium on the basis deoxidized breast limnocalanus casein whey after culturing bacteria and hydrolysate-dairy medium after culturing bacteria) containing bacterial exopolysaccharides (a mixture of laksamana Z, laksamana 1936 and laksamana 1596) in the amount of 8 g/ml, antimicrobial peptides (mixture kazicina And casein is on and irazein) and lectins in the amount of 2.0 mol/l, histamine in the amount of 1.5 mmol/l and short-chain monocarboxylic fatty acids with unbranched chain (a mixture of acetic acid, propionic acid and butyric acid) in an amount of 17 mg/ml

Also received a second composition that represents the environment of the cultivation of bacteria (a mixture of fermented skim milk having a pH of 5.0 to 6.8, and hydrolysate-dairy medium after culturing bacteria) containing bacterial exopolysaccharides (a mixture of laksamana Z, laksamana 1936 and laksamana 1596) in an amount of 5 g/ml, antimicrobial peptides (mixture kazicina And kazicina In and irazein) and lectins in the amount of 0.05 mol/l histamine in the amount of 0.8 mmol/l, short-chain monocarboxylic fatty acids with unbranched chain (a mixture of acetic acid, propionic acid and butyric acid) at 10 mg/ml and targeted supplements (chitosan, lanolin, vaseline oil and olive oil). This composition was made in the form of cream.

Properties of both compositions were investigated in experimental animal models of food Allergy, in combination with eczema and pyoderma produced using inbred line BALB/c mice. In the oral introduction of the first (in this example) obtained composition, and applying the second (in this example) obtained composition to areas of the rash on the auger experimental animals animals was normalized consistency of feces, resolved eczematous rashes and symptoms of pyoderma. Marked off in the gut fungi of the genus Candida, and the elimination of the pathogen pyoderma - Streptococcus pyogenes. Improved immunological parameters of experimental animals (including normalized ratio of CD4 - and CD8-cells, the response of besttransport lymphocytes, decreased levels of specific IgE). Decreased values of degranulation of peritoneal mast cells. Decreased levels of histamine in the content of the intestine. In the samples of the epidermis and dermis derived from permitted lesions, histological examination revealed no signs of inflammatory reaction. Thus was established the combination of antibacterial, immunomodulatory, anti-allergic and anti-inflammatory activity of the compositions.

Example 4. The resulting composition, which represents the environment of the cultivation of lactic acid bacteria (a mixture of fermented skim milk having a pH of 5.0 to 6.8, environment-based deoxidized breast limnocalanus casein whey after culturing bacteria and hydrolysate-dairy medium after culturing bacteria) containing bacterial exopolysaccharides (a mixture of laksamana Z, laksamana 1936 and laksamana 1596) in an amount of 10 g/ml, antimicrobial peptides (mixture kazicina And kazicina In and IMR is CIDIN) and lectins in the amount of 2.5 mol/l, histamine in the amount of 2.0 mmol/l, short-chain monocarboxylic fatty acids with unbranched chain (a mixture of acetic acid, propionic acid and butyric acid) in an amount of 20 mg/ml and the target additives (glycerol, chinosol, licorice root extract, rosehip extract and kaolin). This composition was made in the form of suspension.

The properties of the composition were investigated in the experimental animal model of food Allergy, in combination with eczema and pyoderma produced using inbred line BALB/c mice. In the oral administration of the obtained composition and its application to areas of rash on the skin of experimental animals animals was normalized consistency of feces, resolved eczematous rashes and symptoms of pyoderma. Marked off in the gut fungi of the genus Candida, and the elimination of the pathogen pyoderma - Streptococcus pyogenes. Improved immunological parameters of experimental animals (including normalized ratio of CD4 - and CD8-cells, the response of besttransport lymphocytes, decreased levels of specific IgE). Decreased values of degranulation of peritoneal mast cells. Decreased levels of histamine in the content of the intestine. In the samples of the epidermis and dermis derived from permitted lesions, histological examination not new the Leno signs of inflammatory reaction. Thus was established the combination of antibacterial, immunomodulatory, anti-allergic and anti-inflammatory actions of the obtained composition.

Example 5. The resulting composition, which represents the environment of the cultivation of lactic acid bacteria (cultured nonfat evaporated 10-20% milk having a pH of 5.0 to 6.8) containing bacterial exopolysaccharides (a mixture of laksamana Z, laksamana 1936 and laksamana 1596) in the amount of 8 g/ml, antimicrobial peptides (mixture kazicina And kazicina In and irazein) and lectins in the amount of 1.8 mol/l histamine in the amount of 1.4 mmol/l, short-chain monocarboxylic fatty acids with unbranched chain (a mixture of acetic acid, propionic acid and butyric acid) 16 mg/ml and targeted supplements (infusion of sage, glycerin, chinosol, licorice root extract, rosehip extract, Aerosil, confectionery fat, and olive oil). This composition was made in the form of paste.

The properties of the composition were studied in experimental animal models of food Allergy in combination with eczema and pyoderma produced using inbred line BALB/c mice. In the oral administration of the obtained composition (as a food paste and applied on the lesions lesions on the skin of experimental animals (as a means to N. the outer application) in animals was normalized consistency of feces, resolved eczematous rashes and symptoms of pyoderma. Marked off in the gut fungi of the genus Candida, and the elimination of the pathogen pyoderma - Streptococcus pyogenes. Improved immunological parameters of experimental animals (including normalized ratio of CD4 - and CD8-cells, the response of besttransport lymphocytes, decreased levels of specific IgE). Decreased values of degranulation of peritoneal mast cells. Decreased levels of histamine in the content of the intestine. In the samples of the epidermis and dermis derived from permitted lesions, histological examination revealed no signs of inflammatory reaction. Thus was established the combination of antibacterial, immunomodulatory, anti-allergic and anti-inflammatory actions of the obtained composition.

The examples show the advantages of the proposed technical solution in comparison with the prototype, which consists in the combination in the composition of the metabolic products of bacteria possessing a complementary antibacterial, immunomodulatory, anti-allergic and anti-inflammatory action.

1. The composition having antibacterial, immune stimulating, anti-allergic and anti-inflammatory effect, containing useful for human body products vital the ti bacteria in the form of exometabolites and products of enzymatic lysis by, characterized in that it represents the environment of the cultivation of lactic acid bacteria containing lakaran in the amount of 5-10 g/ml, casticin, irazein or their mixture and lectins in the amount of 0.05-2.5 mol/l histamine in the amount of 0.8 to 2.0 mmol/l and monocarboxylic fatty acids with unbranched chain, namely, acetic acid, propionic acid, butyric acid and valeric acid in a dose of 10-20 mg/ml

2. The composition according to p. 1, characterized in that it contains the environment of the cultivation of bacteria selected from the range: fermented milk having a fat content of 0.5-1.5% and pH 5.0 to 6.8, fermented milk having a pH of 5.0 to 6.8, fermented skim, evaporated 10-20% milk having a pH of 5.0 to 6.8, based environment deoxidized breast means of hydrochloric acid casein whey after culturing bacteria, based environment deoxidized breast molochnokislogo casein whey after culturing bacteria, based environment deoxidized breast limnocalanus casein whey after culturing bacteria, casein-yeast medium after culturing bacteria, hydrolysate-dairy medium after culturing bacteria or mixtures thereof.

3. The composition according to p. 1, characterized in that it contains lakaran selected from range: lakaran Z, lakaran 1936, lakaran 1596 or their mixture.

4. Composition under item 1, the tives such as those it contains casticin selected from the range: casticin And casticin or In their mixture.



 

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2 cl, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the chemical-pharmaceutical industry and represents a method of obtaining a complex preparation for the application in veterinary, possessing immunomodulating and antiseptic properties, which includes mixing succinic acid, levamisole and formalin in distilled water with the following component ratio, wt %: levamisole - 3.0%-3.5%; succinic acid - 2.0%-2.5%; formalin - 0.3%-0.5%, distilled water - the remaining part; sterilisation of the solution by autoclaving is performed in a mode of 1 atm for 20 minutes.

EFFECT: elaboration of the method of obtaining the complex preparation for the application in veterinary, possessing immunomodulating and antiseptic properties.

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed group of inventions relates to medicine, namely to therapy and immunology, and deals with treatment of autoimmune diseases. For this purpose 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxy-1,2-benzisoxazol-6-yl)methoxy)phenyl)propionic acid or its salt is introduced in the form of a combination or a pharmaceutical composition with one or more of TNFα inhibitors.

EFFECT: invention provides efficient treatment of autoimmune diseases due to synergic action of the said components.

6 cl, 1 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical industry, namely to a personal preparation from earthworms for treatment of diabetes. The method of obtaining the personal preparation from earthworms for treatment of diabetes includes placement of sexually mature earthworms in a medium, consisting of organics, which additionally contains a solution of a patient's urine, after that, the sexually mature earthworms are removed and for 3 months each 7-10 days fresh organic food is added to the remaining mass, after that, the sexually mature earthworms are separated, placed in a reservoir and sprayed with an alcohol solution, mixed, poured with the alcohol solution and placed into dark place under the specified temperature, with the solution being mixed daily, with further separation of the extract from the sediment. The personal preparation for treatment of diabetes.

EFFECT: application of the described above preparation increases efficiency of diabetes treatment.

3 cl, 3 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically to a pharmaceutical composition possessing antithrombotic, thrombolytic, immunomodulatory, anti-inflammatory action, normalising lipid and carbohydrate metabolism, more specifically to the pharmaceutical composition of the substance Pijavitum (hereinafter referred to Pijavitum) made from lyophilised medicinal leech. The above pharmaceutical composition is presented in the form of an enteric coated tablet.

EFFECT: coating prevents the active ingredients of Pijavitum from destruction under action of the enzymes and acid medium of the stomach.

FIELD: medicine.

SUBSTANCE: presented group of inventions refers to medicine. What is presented is a method of treating visceral pain and/or one or more symptoms of visceral pain, involving administering a therapeutically effective amount of an antagonist antibody against calcitonin gene-related peptide (CGRP) into an individual suffering visceral pain, or an individual suffering a risk of visceral pain, wherein the CGRP agonist antibody is applicable for peripheral administration. What is also presented is a pharmaceutical composition containing the CGRP agonist antibody and a pharmaceutically acceptable carrier, applicable for peripheral administration.

EFFECT: presented group of inventions provides the effective treatment of visceral pain with using no opiates.

18 cl, 3 dwg, 2 tbl, 3 ex

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