Method for preparing water-soluble fractions of mannoproteins and β-glucan

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to a method for preparing water-soluble fractions of mannoproteins and β-glucan. A method for preparing the water-soluble fractions of mannoproteins and β-glucan consisting in the fact that yeast biomass is prepared by mechanical activation in activators and mills; the prepared mechanical complex is added with a solution of enzymic complex showing β-glucanase or protease activity; that is followed by hydrolysis; the prepared hydrolysate is divided into mannoprotein and β-glucan fractions to be subject to purification under certain conditions.

EFFECT: method provides the more effective hydrolysis and higher yield of the end product.

2 cl, 4 dwg, 10 ex

 

The invention can be obtained from yeast biomass of Saccharomyces cerevisiae preparations based on water-soluble mannoproteins and β-glucan, which without additional purification can be used in cosmetics, food industry, livestock to prevent infections, as well as in immunology.

The cell wall of the yeast S. cerevisiae is a supramolecular complex composed mainly of β-glucan and mannoproteins. Mannoprotein, in turn, consist of protein and mannanoligosaccharides part.

β-Glucan is a polymer of series-connected β-1,3-linkage of glucose monomers (figure 1). Polymer chain β-1,3-glucans are connected to each other via a β-1,6-linkages in complex mesh structure. Thanks largely to the structure of β-1,3-glucan provides rigidity and strength of the cell wall, and its resistance to environmental influences. β-1,3-Glucan can be selectively hydrolyze enzymes exhibiting 1,3-glucanase activity.

Due to its physico-chemical properties of β-glucans are widely used in cosmetics and food industry, for example, as components of creams and diets enriched slabozavisimymi dietary fiber, as well as a substance that stimulates the nonspecific immune response.

Mannoprotein (rarely used by those who rpm the mannans) are distinguished by the form of the chemical bond mannanoligosaccharides part with the protein part. It is most common in the cell wall of Saccharomyces cerevisiae two types of mannoproteins: O-linked, in which connection mannanoligosaccharides part to protein occurs via O-glycosidic bonds between the residue of mannanoligosaccharide and hydroxyl group of serine or threonine (figure 2), and N-linked Mannoprotein with N-glycosidic bond between N-acetylglucosamine and β-amide nitrogen of asparagine (figure 3).

From literature it is known that O-glycosidic bond of mannoproteins easily destroyed by the action of dilute solutions of alkalis (β-elimination) figure 4). Enough processing 0.1-0.5 M sodium hydroxide for 12 hours to split oligosaccharide component from protein. N-linked mannanoligosaccharide, in contrast, can be derived from a protein molecule only under the action of specific enzymes - EndoH-EndoF-field of glycosidase inhibition. However, under the action of alkali N-mannanoligosaccharide extracted from the cell wall together with the protein component. A necessary condition for extraction is the disordering of the cell wall of yeast caused by mechanical processing in energonaprjazhenie the activators or hydrolysis structure of β-glucan.

It is known that mannoprotein by Mann the oligosaccharide fragments interact with specific proteins (pectin) on the surface of pathogenic bacteria and prevent their reinforcement on the mucous membranes of the body, for example in the digestive tract or oral cavity. Unattached bacteria are not able to cause disease, do not reproduce and are quickly eliminated from the body or die.

Supramolecular structure of the cell wall of the yeast S. cerevisiae is constructed in such a way that mannoprotein largely integrated into the β-glucan layer and to convert them into biologically available water-soluble form, you must destroy the relationship mannoproteins with β-glucan. This is done using various methods, such as induced autolysis, enzymatic or acid hydrolysis.

Known invention EN 2406516 C1 from 20.12.2010 where from get yeast biomass antibacterial preparation containing mannoprotein integrated into the cell wall. For this purpose, the mechanical activation of the yeast biomass in conjunction with enzyme complex with depolymerase activity to β-glucan and subsequent solid-phase enzymatic hydrolysis.

As a result of mechanical activation is obtained composites in Fe-GA, representing yeast cells with evenly distributed among them, enzyme complex. In subsequent enzymatic hydrolysis lactone wall only partially hydrolyzed, translating mannoprotein, integrated into the wall, bioavailable, but not in rastvorimae state.

The disadvantage of this technical solution is inefficient use of mechanical activation. Because of the need to conduct processing in low-energy conditions that were not denaturiruet enzymes, disordering of the structure of cell walls practically does not occur and the subsequent enzymatic hydrolysis is not facilitated. Also, hydrolysis of the walls is not completely that affects biological activities of mannans.

The closest technical solution chosen for the prototype is the way to obtain β-glucans and mannans described in Pat. USA No. 7.048.937 B2 (23.05.2006). The way the prototype includes 3 stages:

1. Preparation of biomass to enzymatic hydrolysis: the autolysis of microbial (including yeast) biomass at 35-55°C for cell disruption and receive cell walls. Is carried out within 24-36 hours at a pH of from 4 to 8. The obtained cell walls are separated by centrifugation and subjected to enzymatic hydrolysis.

2. Enzymatic hydrolysis is added to the reaction mixture containing the cell wall, enzymes (alkaline protease, glucoamylase, amylase, amyloglucosidase, lipase). In the hydrolysis of part of the protein and β-glucan in the cell walls of hydrolyzed and becomes available for separation into two fractions. The hydrolysate centrifuge the comfort, while β-glucan precipitates and is dried by spray drying, and mannoprotein remain in the supernatant, which is used for ultrafiltration and highlight mannoproteins.

3. The separation into fractions: ultrafiltration extract at a molecular sieves allows you to select mannoprotein with a molecular mass higher than 10 D. The resulting mannoprotein dried by spray drying.

So get preparation of mannans, which contains at least 85 wt.% mannoproteins with a molecular mass higher than 10 D and the preparation of β-glucan, which contains about 65 wt.% β-glucan.

The method of producing mannoproteins and β-glucan on the prototype has significant drawbacks. To prepare the biomass method of autolysis in the liquid phase and obtain a semi-product of the destroyed cell walls require large amounts of water. The process of autolysis in the liquid phase is not economically efficient because it takes a long time (more than a day) to maintain a high temperature (about 50°C) the reaction mixture, and then separating the precipitate of the cell wall from the liquid phase. It is also known that to increase the speed of autolysis to the reaction mixture flammable and toxic organic solvents.

The use of alkaline proteases at the stage of enzymatic hydrolysis of cell walls causes n is a need in alkaline (9 to 10) the pH of the reaction medium. Under these conditions, low-molecular-weight 0-mannanoligosaccharide hatshepsuts from protein molecules and pass into solution. When ultrafiltration molecular sieves of this type of mannanoligosaccharides is removed and discarded together with the ballast substances. Thus, the preparation of mannoproteins received the prototype includes only high-molecular N-mannanoligosaccharide that reduces the biological activity of the drug received. In addition, the preparations contain 85 and 65% of mannoproteins and β-glucan, respectively, which necessitates further purification with the aim of obtaining purified preparations for use in cosmetics and immunology.

The problem solved by the claimed technical solution is to design clean, simple method of obtaining a purified preparations based on water-soluble mannoproteins and β-glucan.

The method of obtaining must allow the use of available raw materials such as biomass feed yeast, spent yeast biomass, distillery grains, etc. For better ways to obtain drugs in the prototype requires the preparation of yeast biomass, namely the destruction of the cell walls of yeast was carried out without carrying out of autolysis in the liquid phase, and at the stage of enzymatic hydrolysis was used armenti, exhibiting the highest activity at pH<7. For use in cosmetics and immunology mannoproteins and β-glucan should be further refined ballast substances with the potential to cause allergic reactions.

The problem is solved thanks to the present method, including the preparation of yeast biomass to enzymatic hydrolysis, enzymatic hydrolysis, separation into fractions, treatment, characterized in that the biomass of yeast previously subjected to mechanical activation activators or mills, providing faster grinding media 60-600 m/S2 when the residence time in the treatment zone of 0.5-15 minutes, to the resulting composites in Fe-GA add a solution of the enzyme complex, exhibiting β-glucanase or protease activity, the enzymatic hydrolysis is carried out at pH 4-7, the concentration of the enzyme complex of 0.5-10 wt.%, the concentration of the obtained composites in Fe-GA 5-20 wt.%, at a temperature of 50-65°C for 10-30 hours, the resulting hydrolysate is separated into mannoproteins and β-glucan fraction, which is subjected to further purification.

Preferably, the mechanical activation of the biomass is carried out in the activators planetary centrifugal or vibratory centrifugal types, or roller mills.

During the mechanical activation of the yeast biomass pointed to by the x high-energy conditions is a mechanical destruction of cells and a significant disordering of the supramolecular structure of cell walls, increase their reactivity with respect to enzymatic hydrolysis. Also, in the obtained composites in Fe-GA - product of mechanical activation is implemented reduced diffusion path, the structural layers of the cell wall are diffuse in nature.

Selection of equipment for mechanical activation is not accidental and is aimed at the achievement of the preset patterns of the composites in Fe-GA. Conditions of mechanical activation and the equipment is not obvious and cannot be picked up by a simple enumeration of the modes without conducting a comprehensive study of the structure and disordering of the walls of the yeast biomass.

Mechanical method of preparing yeast biomass to enzymatic hydrolysis, namely getting destroyed cell walls more cost-effective than autolysis in the liquid phase as it requires large quantities of water, prolonged maintenance of high temperature, as well as the stage of isolation of cell walls from the autolysate. Intermediate destroyed cell walls obtained after mechanical activation is an air dry powder from beige to light brown in color, which can be directly used for further enzymatic hydrolysis.

Enzymatic hydrolysis of the intermediate product, obtained as a result of mechanical activation, with the help of ven is the ATA, showing β-glucanase and protease activity allows you to break the chemical bond between mannoproteins part and structure-forming β-glutinosae part. Consequence of the destruction of chemical bonds between these components is that they can be split into two fractions. In addition, conducting hydrolysis of the enzyme preparations, active in the pH range 4-7 allows you to save low-molecular O-mannanoligosaccharide part mannoproteins faction, which, of course, increases the biological activity of the substances obtained in comparison with the products of the prototype.

The clearance of water-soluble mannoproteins and β-glucan in the described modes allows to obtain products with higher than in the prototype, content mannoproteins and β-glucan. More concentrated, and purified preparations have greater biological activity and contain less ballast substances that can potentially cause allergic reactions. So, cleaned mannoproteins the product has the following composition: water-soluble mannoprotein - 85-90 wt.%, β-glucan - 2-4 wt.%, ash - 3-6 wt.%, water - the rest. Purified β-glucan preparation has the following composition: β-glucan - 75-80, proteins 10-13, ash - 5-7 wt.%, water - the rest.

The set of essential characteristics savla what constituent of the way among the known prototypes have been identified, that allows to make a conclusion on the conformity of the proposed method the criterion of "inventive step" and "novelty."

Technical result achieved is to obtain biologically active compounds based on water-soluble mannoproteins and β-glucan having high purity, using the proposed environmentally friendly and easy way.

The invention is illustrated by the following examples.

Example 1.

Dried to a moisture content of 10 wt.% pressed bakery yeast GOST 171-81 mechanically activated in a flow activator centrifugal type TSEM, or vibratory centrifugal type VCM, or roller mill providing faster grinding media 60 m/s2and the residence time in the treatment area of 0.5 minutes. The resulting intermediate is mixed with an enzyme complex Cellolux-A (production Sibbiopharm Ltd Berdsk)with β-glucanase activity, in a ratio of 99.5/0.5 in. To the mixture add a buffer solution with a pH of 4-6 and the concentration of the solid phase 5 wt.% and carry out the enzymatic hydrolysis for 10 hours at 50°C.

When accelerating particles less than 60 m/s2not provided sufficient razuporyadochennoi supramolecular structures in the cell walls of yeast biomass, which reduces the efficiency of the subsequent enzymatic hydrolysis.

The application is the processing of less than 0.5 minutes does not provide the required degree of destruction of the yeast cells, accumulation of mechanical energy and virtually no leads to the formation of composites in Fe-GA. Lowering the temperature of the enzymatic hydrolysis below 50°C adversely affects the velocity of hydrolysis, and the conduct of the warm-up in less than 10 hours, does not provide the optimum degree of conversion. Lowering the concentration of the solid phase is less than 5 wt.% not advisable for economic reasons, as associated with the subsequent need for removal of excess volume of water.

Example 2.

Dried to a moisture content of 10 wt.% pressed bakery yeast GOST 171-81 mechanically activated in a flow activator centrifugal type TSEM, or vibratory centrifugal type VCM, or roller mill provides acceleration of milling bodies of 600 m/s2and the residence time in the treatment area 15 minutes. The resulting intermediate is mixed with an enzyme complex Cellolux-A (production Sibbiopharm Ltd Berdsk)with β-glucanase activity, in a ratio of 9/1. To the mixture add a buffer solution with a pH of 4-6 and the concentration of the solid phase 20 wt.% and carry out the enzymatic hydrolysis for 20 hours at 65°C.

When accelerating over 600 m/s2leads to heating of the treated biomass, which can lead to the destruction of biologically active mannoproteins. Application processing more than 15 minutes that the same may lead to mechanochemically target components. The temperature increase of the enzymatic hydrolysis above 65°C leads to denaturation of enzyme complexes. Increase warm-up time of over 20 hours inconsequential effect on the degree of transformation due to the gradual decrease of the reaction rate from time to time. Increasing the concentration of the solid phase is more than 20 wt.% not advisable due to the high viscosity of the reaction mixture.

Example 3.

Is carried out under the conditions of example 2. As the enzymatic complex uses a mixture of enzymatic complex Cellolux And"possessing β-glucanase activity, and enzymatic complex It G3x" (production Sibbiopharm Ltd Berdsk), by having activity against proteins of the cell wall. The optimum temperature for carrying out enzymatic hydrolysis for this enzymatic complex 60°C, optimum pH 6-7. The duration of reaction for 15 hours.

The use of a mixture of enzyme complexes with β-glucanases and by activity, can increase the rate of the enzymatic hydrolysis of the cell wall due to the integrated effect of all of its structural components.

Example 4.

Is carried out under the conditions of example 1-2. As a mechanical activator use the activator of the planetary type, AGO-2, which yields in La is oratorial small party product for research and development stages.

Example 5.

Is carried out under the conditions of example 2. The raw material used yeast biomass distillery stillage is dried to a moisture content of 10 wt.%. Due to the presence in yeast biomass distillery stillage compounds that can inactivate the enzymatic complex, complicating the course of enzymatic hydrolysis, it is advisable to use yeast biomass and enzymatic complex with β-glucanase activity, in a ratio of 90/10. The duration of the reaction is in this case 30 hours. Involvement in the production of cheap and substandard raw materials allows us to rationally disposed listed waste, and also reduce the cost of obtaining the drug.

Example 6.

Is carried out under the conditions of example 2-3. In used as the raw material biomass of fodder yeast, dried to a moisture content of 10 wt.%. Due to the availability of fodder yeast hardened cell walls, it is advisable to use intensive modes of mechanical activation and the mixture of enzyme complexes with β-glucanases and by activity. The ratio intensively activated biomass of fodder yeast mixture and enzymatic complexes is 98/2. The duration of reaction is 20 hours. Involvement in the production of cheap feedstock reduces the costs for the doctrine of the drug.

Example 7

Is carried out under the conditions of example 1-3. The product obtained by enzymatic hydrolysis centrifuged for 10 minutes at 5000 rpm./minutes the Precipitate containing β-glucan, washed with a solution of 0.005-0.01 M sodium hydroxide with a gradual decrease in concentration, and then distilled water. The purified preparation of β-glucan is dried by spray drying or vacuum drying oven at a temperature not exceeding 50°C.

The resulting product contains, wt%:

β-glucan - 80%,

protein - 10%,

ash - 5%,

water - the rest.

Example 8.

Is carried out under the conditions of examples 1-3. The product obtained by enzymatic hydrolysis centrifuged for 10 minutes at 5000 rpm./minutes the Supernatant containing mannoprotein, filtered over a molecular sieve, retaining molecules with a molecular mass of more than 10 kDa and repeatedly washed with a solution of "25 wt.% distilled water / 75 wt.% ethyl alcohol" to achieve transparent wash water. The purified preparation containing mannoprotein, dried by spray drying or vacuum drying oven at a temperature not exceeding 50°C.

The resulting product contains, wt%:

water-soluble mannoprotein - 90%,

β-glucan - 2%,

ash - 3%,

water - the rest.

Example 9.

Is carried out under the conditions of example 5-6. The product obtained as a result of enzymatic hydrolysis, centrifuged for 10 minutes at 5000 rpm./minutes the Precipitate containing β-glucan, washed with a solution of 0.005-0.01 M sodium hydroxide with a gradual decrease in concentration, and then distilled water. The purified preparation of β-glucan is dried by spray drying or vacuum drying oven at a temperature not exceeding 50°C.

The resulting product contains, wt%:

β-glucan - 75%,

protein - 13%,

ash 7%,and

water - the rest.

Example 10.

Is carried out under the conditions of example 5-6. The product obtained by enzymatic hydrolysis, centrifuged for 10 minutes at 5000 rpm./minutes the Supernatant containing mannoprotein, filtered over a molecular sieve, retaining molecules with a molecular mass of more than 10 kDa and repeatedly washed with a solution of "25 wt.% distilled water / 75 wt.% ethyl alcohol" to achieve transparent wash water. The purified preparation containing mannoprotein, dried by spray drying or vacuum drying oven at a temperature not exceeding 50°C.

The resulting product contains, wt%:

water-soluble mannoprotein - 85%,

β-glucan - 4%,

ash - 6%,

water - the rest.

Sources of information

1. Biorndal H., Lindberg C. The Structure of a β-(1-6)-D-glucan from yeast cell walls // Biochem. J. - 1973. No .135. - P.31-36.

2. Manners D.J., A.J. Masson, J.C. Patterson The structure of a β-(1-3)-D-glucan from yeast cell walls // Biochem. J. - 1973. No. 135. - P.19-30.

3. Biryuzova streets V.I. Ultrastructural organization of the yeast cells / M.: Nauka, 1993. - 224 S.

4. Kalabina T.S., Kulaev, I.S. Role of proteins in the formation of the molecular structure of the cell wall of yeast // Advances in biological chemistry. - 2001. No. .41. - S-130.

5. Kitamura, K., Matsuki, S., Tanabe K. Physiologically active polysaccharides, ad production use thereof// Pat. USA. No. 4.313.934.-2.02.1982.

6. Nakakuki So Present status and future prospects of functional oligosaccharide development in Japan // J. Appl. Glycosci. - 2005. No. 52. - P.267-271.

7. Warrand J. Healthy polysaccharides. The next chapter in food products // Food technol. Biotechnol. - 2006. No. 44. - P.355-370.

8. Glycoproteins, Ed. by A. Gottschalk, T1./M.: Mir, 1969. - 304 S.

9. Fairchild A.S., J.L. Grimes, F.T. Jones, Winel M.J., F.W. Edens, Sefton, A.E. Effects of hen age, Bio-Mos, and Flavomycin on poult susceptibility to oral Escherichia coli challenge // J. Poultry Sci. - 2001. No. 80. - P.562-571.

10. Firon, N., Oftek I., Sharon N. Carbohydrate specificity of the surface lectins of Escherichia coli, Klebsiella pneumoniae, and Salmonella typhimurium II Carbohydrate research - 1983. - No. 120. - P.235-249.

11. Smith, S., A.D. Elbein, Y.T. Pan Inhibition of bacterial binding by high-mannose oligosaccharides // Pat. USA. No. 5.939.279. - 17.08.1999.

12. Tzipori S. The relative importance of enteric pathogen affecting neonates of domestic animals // Adv. in vet. sc. compare med. - 1985. No. 29. - P.103-206.

13. Dawson K.A., Sefton, A.E. Methods and composition for control of coccidiosis // Pat. USA. No. 7.048.937.B2. - 23.05.2006.

14. Sedmak J.J. Production of beta-glucans and mannans // Pat. USA. No. 2006/0263415 .A1. - 23.11.2006.

15. Belousova N, Gordienko, S. C., Eroshin VK, Ilchenko VIA Obtaining mixtures of amino acids on the basis of the autolysates of yeast Saccharomyces grown on ethanol or sugars // Biotechnology. - 1990. No. 3. - P.6-9.

1. With the persons receiving the water-soluble fractions of mannoproteins and β-glucan, including the preparation of yeast biomass to enzymatic hydrolysis, enzymatic hydrolysis, separation into fractions, treatment, characterized in that the biomass of yeast previously subjected to mechanical activation activators or mills, providing faster grinding media 60-600 m/s2when the residence time in the treatment zone of 0.5-15 min, to the resulting composites in Fe-GA add a solution of the enzyme complex, exhibiting β-glucanase or protease activity to the concentration of the complex of 0.5-10 wt.%, and buffer solution with a pH of 4-7, and the concentration of the solid phase 5-20 wt.%, the hydrolysis is carried out at a temperature of 50-65°C for 10-30 h, the resulting hydrolysate is separated into mannoproteins and β-glucan fraction, which is subjected to further purification.

2. The method according to claim 1, characterized in that the mechanical activation of the yeast biomass is carried out in the activators planetary centrifugal or vibratory centrifugal type or roller mills.



 

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FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely dermatology and can be used for treating generalised vasculitis accompanying neuroinfections in children. That is ensured by parenteral antibacterial or antiviral therapy. The acuity requires additional prescription of parenteral administration of cytoflavin 0.6-1.0 ml per kg of body weight daily for 5 days combined with antibacterial or antiviral therapy. It is followed by early reconvalescence that involves oral administration of sulodexide 1 capsule a day for children between the ages of 5 to 12. For children of 12 and older - 2 capsules a day for 1 month. If thrombosis prevails for more than one month, neurodiclovit 2-3 mg per kg of body weight is prescribed orally 2 times a day for 1~2 months.

EFFECT: method provides reduced length of treatment, prevented developing chronic and complication clinical course due to aimed action of vascular preparations on endothelial regeneration and normalisation.

3 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to reflexotherapy. The method involves the prolonged treatment of the reflex therapeutic points. The point treatment is enabled by filler introduction. In the corporal points, the filler is introduced in the amount 0.1-0.4 ml at a point depth. In the auricular points, the filler is introduced in the amount 0.1-0.2 ml subcutaneously or intracutaneously. One of following preparations is used as the filler: a preparation of stabilised hyaluronic acid of non-animal origin, a two-phase (heterogeneous) preparation, a biopolymer gel.

EFFECT: method allows even in a single application of the filler to provide the prolonged treatment of various duration in the absence of complications from such treatment.

8 cl, 5 ex

FIELD: medicine.

SUBSTANCE: there are described mucoadhesive preparations and controlled release preparations consisting of aqueous solutions containing 0.05 wt % to 5 wt % of natural purified xyloglucan-structured polymer, and 10 wt % to 70 wt % of glycerine. The preparations are applicable on human mucous membranes, such as nasal, oral and vaginal mucosa, as humidifying and softening agents, or as a release system of a pharmaceutical drug. There are described pharmaceutical preparations and medical devices applicable on human mucous membranes, containing mucoadhesive preparations and controlled release preparations together with active ingredients and excipients.

EFFECT: preparations are capable to lower or eliminate negative effects, directly and/or indirectly associated with dry mucous membranes.

14 cl, 2 dwg, 9 tbl, 13 ex

FIELD: medicine.

SUBSTANCE: to prevent severe pregnancy complications in thrombopillic patients, 1-2 months prior to planned pregnancy, preparation VESSEL DUE F is introduced in a dose 1000 units/day - 2 tablets twice a day to ensure decrease in lupus anticoagulant (LA) activity by at least 0.8. Then onset of pregnancy follows. During the first pregnancy trimester, VESSEL DUE F is substituted for Clexane injected in abdomen subcutaneously in a dose 0.4 ml/day daily. Starting from thirteenth week of pregnancy, VESSEL DUE F therapy is recommenced in a previous dose - 2 tablets twice a day until delivery. Introduction of VESSEL DUE F is prolonged continue within the first postpartum month.

EFFECT: integrated effect on all the links of haemostasis system, prolonged intake of tableted formulation without side effects on a foetus during pregnancy and lactation.

2 ex

FIELD: medicine.

SUBSTANCE: method involves introducing Sulodexid as coagulant at a dose determined in correspondence with coagulation constant KK. Its value being equal to 6.67±0.21 min, initial Sulodexid dose is equal to 40 LRU/kg/day. KK value being less than 18 min one day later, the initial Sulodexid dose is increased by 5 LRU/kg/day. The value being greater than 30 min, the dose is reduced by 5 LRU/kg/day. No inflammatory phenomena being observed and burn wound epithelialization signs appearing, Sulodexid therapy is cancelled reducing its dose by 1/3 of the initial one.

EFFECT: stable antithrombotic; reduced risk of hemorrhagic and pyoinflammatory complications; early injured skin epithelialization.

1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents pharmaceutical composition for treating gastroesophageal reflux disease, containing at least one proton pump inhibitor and at least one probiotic, wherein the proton pump inhibitor is taken in the amount of 0.05-25 wt % in the composition; and the probiotic is taken in the amount of 10-95 wt %; additive agents up to 100 wt %.

EFFECT: provided preventing Hpylori translocation, avoiding the necessity of Hpylori detection and antibacterial course of eradication, higher safety of the prolonged therapy with the proton pump inhibitors and avoided gastric mucosa atrophy, and a risk of gastric cancer.

5 cl, 10 tbl

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