RU2233320C2 - Method for preparing biologically active preparation, biologically active nutrient supplement with prebiotic effect resulting to correction (leveling) of metabolic syndrome and medicinal preparation for regulation of digestive tract microbiocenosis - Google Patents

Abstract

FIELD: biotechnology, food industry, veterinary science, medicine.

SUBSTANCE: invention relates to producing fodder agents. Method for preparing biologically active supplement involves culturing and immobilization of Saccharomycetaecae biomass on a carrier. Carrier represents mixture of native and extruded cereal crops bran. Biologically active nutrient supplement contains Saccharomyces biomass immobilized on the indicated carrier with porous surface 2.0 m²/g, not less. The concentration of Saccharomyces cells is 10⁹ - 10¹² cells/g, not less. A medicinal preparation comprises biologically active supplement representing components of Saccharomyces cerevisiae cells immobilized on porous carrier of vegetable origin. Medicinal preparation comprises the following components, wt.-%: lipids, 2-5; carbohydrates, 25-50; proteins, vitamins, macroelements and nutrient fibers, the balance. Proteins comprise 10 essential amino acids taken in the amount 30.0-75.0 wt.-% of the total amount of proteins. Vitamins are represented by B₁, B₂, B₃, B₆, PP and C; macroelements: phosphorus, potassium, sodium, magnesium and calcium. Soluble nutrient fibers comprise 45 wt.-%, not less, and insoluble fibers comprise 35 wt.-%, not less. Invention provides preparing biologically active supplement and medicinal preparation with expressed prebiotic properties, high bifido- and lactogenic effects, and sorption properties also.

EFFECT: improved preparing method, valuable properties of preparation.

24 cl, 1 dwg, 15 tbl

Description

A method of obtaining a biologically active drug

The invention relates to microbiology and relates to a method for producing a preparation of the Eubicor type. The Eubicor class of drugs is basically a biologically active additive, the main component of which is the inactivated microorganisms of the Saccharomycetaceae family, cultivated in a specially prepared nutrient medium and forming a biomass placed on a carrier. The scope is both the food industry and the production of feed products, as well as medicine and veterinary medicine.

The well-known "Method for the production of therapeutic and preventive food additives" (RU 2102903, publ. 01/27/98), in which microorganisms are cultivated on edible plant or milk raw materials, at a temperature of 20-40 ° C, Saccharomyces cerevisiae (vini) is taken as microorganisms VKPM U-511. After cultivation, the resulting product acquires a wide range of properties that are valuable in the treatment and prevention of gastrointestinal diseases. However, with such cultivation in the final product, the increase in biomass is not enough to obtain its required substantial increase per unit volume of the carrier of microbial bodies, which significantly reduces the effect of regulation of the endogenous intestinal flora and narrows its regulatory effect. In addition, crushed grain or soya raw materials are used as filler, but not bran in their pure form, which impairs organoleptic properties and bioavailability.

The known "Method for the production of a probiotic for animal husbandry, mainly poultry farming" (RU, patent 2000116, publ. 07.09.93, bull. No. 33-36), including separate cultivation of microorganisms, their drying, followed by mixing with dry monocultures. The drug provides the formation and stabilization of normal digestive tract microbiocenosis. However, it is intended only for the digestive tract of birds. In addition, this method can only receive probiotic preparations, but you cannot get a prebiotic. The known "Method for the preparation of the drug" Sporobacterin "(RU, patent 2056855, publ. 03/27/96, bull. No. 9), including sowing the strain in a nutrient medium, growing the culture to the exponential growth phase, then diluting the culture with fresh nutrient medium to the desired concentration and further preparation of the target product The drug allows you to influence the microbiocenosis of the gastrointestinal tract, for example, to fight against dysbacteriosis caused by pathogenic and conditionally pathogenic bacteria. it manifests itself in the use of the antagonistic activity of the grown biomass of living microorganisms (probiotics), which reduces the environmental friendliness of the obtained product.In addition, the task of obtaining biomass sufficient for the manifestation of its antagonistic properties does not (does not solve the problem) maximize the contaminant surface of the carrier (for the body’s own flora ). Known "A method of obtaining a probiotic for animals and birds" (RU, patent 2018313, publ. 05/06/92, bull. No. 16), including the cultivation of bacteria of a certain type at temperature, inoculum doses and in a nutrient medium and ensuring the growth of biomass, followed by spray drying. The drug provides the formation and stabilization of normal digestive tract microbiocenosis. However, it is intended only for the digestive tract of animals and birds. It allows you to significantly increase the number of microbial bodies per unit volume of the product (cells / g). However, the method is difficult to carry out in an industrial environment due to the slow growth of microbial bodies in culture media and the need to use protective media, without which the properties of biomass change.

The closest technical solution to the claimed invention is the "Method of obtaining a bacterial preparation for the production of feed products" (RU, patent 2035184, publ. 02.01.90, bull. No. 14), including the cultivation of microorganisms, preparation of the inoculum dose and placing it in a nutrient environment, obtaining biomass, culturing biomass on a carrier and drying it together with a carrier to obtain the target product. It allows you to get a product with therapeutic properties, however, it is used for animals. In addition, special protection is required to preserve the properties of biomass. Animal raw materials are used, which increases the risk of introducing harmful bacteria, reduces the environmental friendliness of the product.

The main objective of this method is to obtain an environmentally friendly additive that allows you to qualitatively change the microbiocenosis of the human or animal organism. Moreover, the more microorganisms are placed on the contaminating surface of the carrier, the greater the biomass will be formed on the carrier by increasing the number of yeast metabolism products, for example Saccharomycetaeceae, together with the bodies of the microorganisms themselves. After reaching the threshold value of the number of microorganisms per unit volume of the carrier, the use of such an additive will provide a new, more pronounced positive effect of its effect on the body. The threshold value of the number of microorganisms depends on the surface on which microorganisms can settle in the phase of their exponential growth. In this regard, it is important to maximize the contaminating surface of the carrier, while significantly increasing the sorption capacity of the additive itself and its bioavailability. The problem is solved by the proposed method for producing a biologically active additive (BAA), which consists in obtaining a biologically active additive based on Saccharomycetaeceae biomass and consisting in preparing a nutrient medium, cultivating the seed in a nutrient medium to obtain a seed mass, and placing the seed mass on cereal bran cultures and cultured to obtain the desired concentration of Saccharomycetaeceae cells. Get the target product after inactivation of the biomass and drying. The seed is cultivated in a liquid nutrient medium, which is prepared by mixing malt wort with a density of not more than 15% with drinking water in a ratio of 50 vol.% To 50 vol.%, In two stages, first a preliminary sowing mass is obtained, and then a working sowing mass and bran of cereals is used as a mixture of bran of crops extruded at a pressure of up to 100 kg / cm ² and a temperature of (120-170) ° C and native with a moisture content of 10-15%, with drinking water in a proportion of 1 kg of a mixture of bran of cereals crops for 1.2-1.4 liters of drinking water, preliminary and the working sowing mass is obtained in the form of a liquid inoculum with a concentration of at least 1 · 10 ⁸ cells / ml, while in both stages the inoculum is added to the liquid nutrient medium until an initial concentration of 1 · 10 ⁵ cells / ml is obtained and cultured to the indicated cell concentration, Further, the working sowing mass is placed on a mixture of bran of grain crops in an amount of 20 · 10 ⁹ -40 · 10 ⁹ cells / kg of the mixture and cultivated for 16-18 hours at a temperature of 28-30 ° C and a humidity of 90-100% to a concentration of less than 1 × 10 ⁹ cells / ml and the inactivation of the biomass is carried out infrared radiation at a density of 0.1-2.0 W / cm ² with a wavelength of 4,3-8,2 mm simultaneously with the drying, which is performed at a temperature of 70-85 ° C combined radiation-convection method prior to sufficient humidity 10-15% . It is possible to use bran cereal in proportion, wt.%: Bran cereal extruded - 70-75, bran bran cereal crops - 25-30.

It is possible to use bran bran of crops in proportion, wt.%: Bran bran of extruded crops - 50, bran bran of crops - 50.

It is possible to obtain 7 wt.% Of extruded bran of grain crops and to cultivate 24 hours at a temperature of 28-30 ° C when receiving a preliminary sowing mass in a liquid nutrient medium or to obtain a preliminary sowing mass for 30 hours at a temperature of 28-30 ° C. It is possible, upon receipt of the working sowing mass, to add 7 wt.% Of extruded bran of grain crops to the liquid nutrient medium and cultivate 24 hours at a temperature of 28-30 ° C. It is possible to obtain cultivation during 30 hours at a temperature of 28-30 ° C. Perhaps Saccharomycetaeceae represent a private strain - Saccharomyces. It is possible for Saccharomyces to represent Saccharomyces cerevisiae (vini). It is also possible to use extruded wheat bran or extruded rye bran or extruded buckwheat bran in the method.

The proposed method is as follows.

To obtain a biologically active additive based on biomass, Saccharomycetaeceae cultivates the seed from microorganisms in the form of a seed mass, place the seed mass on bran cereals, which are simultaneously the carrier to obtain the required volume of biomass, cultivate the biomass on the carrier and dry the biomass together with the carrier to obtain target product after inactivation and drying. The proposed method is characterized in that the nutrient medium for producing seed (worker) is used in liquid form, for which malt wort and drinking water are taken as the starting material, a mixture of malt wort with a density of not more than 15% and drinking water as part of the target final product is prepared in the proportion of 50 vol.% to 50 vol.%. Seed is cultivated in a liquid nutrient medium in two stages: first, a preliminary seed mass is obtained, and then a working seed mass is obtained. Cereal bran is used in the form of a mixture of cereal bran, for example, wheat and / or rye, and / or buckwheat, and extruded at a pressure of up to 100 kg / cm ² and a temperature of (120-170) ° C, mixed with native cereal bran and drinking water. In order to obtain the maximum number of microbial bodies in the biomass of the target product can be used in the following proportions: bran cereal extruded 70-75 wt.%; bran cereals native 25-30 wt.%; drinking water 1.2-1.4 l per 1 kg of bran mixture with a moisture content of 10-15% or in another ratio: bran cereal extruded 50 wt.% and bran bran cereal 50 wt.%; drinking water 1.2-1.4 l per 1 kg of bran mixture with a moisture content of 10-15%. At the same time, seed from microorganisms is cultivated on the seed mass in two stages. When using a liquid nutrient medium, when preparing preliminary seed, the seed (preliminary) is first prepared using Saccharomycetaeceae, in the form of an inoculum with a concentration of at least 1 · 10 ⁸ cells / ml, for which microorganisms inoculate a liquid nutrient medium at a rate of 1 · 10 ⁵ cells / ml with the addition of 7 wt.% of the feedstock and cultured for 24 hours at a temperature of 28-30 ° C, where pre-extruded bran of grain crops is taken as the feedstock. Or without adding 7 wt.%, But then cultivate up to 30 hours. Then, seed material (worker) is prepared with a concentration of microorganisms of at least 1 · 10 ⁸ cells / 1 ml, for which an inoculum with a concentration of microorganisms is introduced into a liquid nutrient medium of the same composition not less than 1 × 10 ^8/1 ml in a proportion of inoculum to a liquid medium 10 to 1 by volume, and the liquid culture medium was added 7 wt.% of the feedstock in the form of pre-extruded cereal bran and cultured for 24 hours at a temperature of 28-30 ° C to obtain 1 × 10 ⁵ cells / ml They can be cultured without adding 7 wt.%, But for up to 30 hours. Then, biomass on the carrier is cultivated to obtain an initial mixture with a concentration of microorganisms in the initial mixture of at least 1 · 10 ⁹ cells / ml, for which seed (worker) is introduced into the carrier with a concentration of microorganisms per 1 kg of carrier 20 · 10 ⁹ -40 · 10 ⁹ biomass cells, fermented for 16-18 hours at a temperature of 28-30 ° C and a humidity of 90-100% to obtain biomass in the required effective ratio of biomass to filler. Then, the target product is obtained, for which the initial mixture is dried at a temperature of 70-85 ° C until a moisture content of 10-15% is obtained by the combined radiation-convection method, and at the same time, the biomass is inactivated with drying at an infrared radiation density of (0.1-2.0) W / cm ² with a wavelength of (4.3-8.2) microns at the same time as drying. In addition, wheat and / or rye bran and / or buckwheat bran, which is mixed with wheat bran and / or rye and / or buckwheat bran native and drinking water in the proportion of: wheat bran and / or extruded rye bran and / or bran buckwheat 70-75 wt.%; wheat bran and / or rye bran and / or bran buckwheat native 25-30 wt.%; drinking water 1.2-1.4 l per 1 kg of bran mixture with a moisture content of 10-15%. Either wheat and / or rye bran and / or bran buckwheat bran, which is mixed with wheat bran and / or rye bran and / or native buckwheat bran in the proportion of: wheat and / or rye bran, is taken as a feedstock for the carrier of microorganisms: bran and / or bran buckwheat extruded - 50 wt.%, wheat bran and / or rye bran and / or bran buckwheat native 50 wt.%; drinking water 1.2-1.4 l per 1 kg of bran mixture with a moisture content of 10-15%. And as the raw material for the seed can take pre-extruded wheat and / or rye bran and / or bran buckwheat and add them in an amount of 7 wt.%. Or, to prepare the seed (preliminary) in the form of an inoculum, microorganisms are cultured for up to 30 hours at a temperature of 28-30 ° C in a liquid nutrient medium from a mixture of malt wort with a density of not more than 15% and drinking water in a ratio of 50 vol.% To 50 vol.% . Inoculum can be prepared using Saccharomycetaeceae-Saccharomyces as seed, or inoculum prepared using Saccharomyces-Saccharomyces cerevisiae (vini). Extruded wheat and / or rye bran and / or buckwheat bran can be used as a starting material for the carrier and add them in an amount of 7 wt.%. To obtain seed (worker), the inoculum can be cultured for no more than 30 hours at a temperature of 28-30 ° C in a liquid nutrient medium from a mixture of malt wort with a density of not more than 15% and drinking water in a ratio of 50 vol.% To 50 vol.% . The proposed method allows to increase the contaminating surface of the carrier of microorganisms to significantly increase the biomass of microbial bodies (microorganisms), as well as the number of microbial bodies per unit volume of the carrier of microbial bodies and biomass while reducing the cultivation time, increasing the sorption capacity of the target product. This technical result provides an increase in biomass by increasing the number of microbial bodies of microorganisms per unit volume of the target product while increasing the absorption capacity of the target product and improving the bioavailability of the target product.

In the tables reflecting the growth dynamics of microorganisms, are shown:

Table 1. The dependence of the productivity of yeast on the solid phase (75 wt.% Extruded, 25 wt.% Native) on the initial concentration No, applied to the solid phase of the composition of the nutrient medium to obtain seed. The ratio of solid phase and liquid is 1: 1.3. The cultivation time is 16-18 hours.

Table 2. The growth dynamics of yeast in liquid nutrient media.

Table 3. The choice of inoculum dilution in stepwise preparation of seed.

Table 4. The dependence of the productivity of the yeast on the moisture content of the substrate (on the volume of liquid introduced per 1 kg of a mixture of dry bran) N _o = 5.0 · 10 ⁷ cells / ml. The cultivation time is 16-18 hours.

Table 5. The dependence of yeast productivity on the composition of the solid phase and the cultivation time N = 5.0 · 10 ⁷ cells / ml; the ratio of solid phase and liquid is 1: 1.

To implement the proposed method for the preparation of a biologically active preparation, bran bran, for example, wheat and / or rye, which themselves are a source of valuable plant substances containing saccharides, polysaccharides, triglycerides and other biological substances, is selected in advance when preparing the carrier. Due to the special treatment of bran, the very structure of the bran flakes changes, it acquires a finely dispersed character, and the surface of the microorganism carrier increases many times. When processing flakes with high pressure, up to 100 kg / cm ² and a temperature of (120-170) · Cells of plant matter break and tens to hundreds of times increase their surface. The large contamination surface of the carrier allows, at the stage of exponential growth of microorganisms inhabited on this carrier, to significantly extend the time of their active reproduction, since growth does not stop due to the self-poisoning of microorganisms by their own metabolites. As a result of accelerated and longer exponential growth of microorganisms, the contamination surface is populated by 80-90%, which, in turn, increases the biomass, and the number of microbial bodies per unit volume of the carrier increases significantly.

Table 1 shows the dependence of yeast productivity on the composition of the solid phase. Due to this property of the carrier, it is possible to cultivate microorganisms, for example, Saccharomyces cerevisiae, using a combination of extruded and native bran to obtain a high predetermined concentration of microorganisms in the final product. The table shows that the increase in the number of microorganisms per unit of contaminating surface depends on the optimal ratio of native and extruded bran relative to the cultivation time.

The process of obtaining seed consists of two stages: obtaining a preliminary seed in the form of an inoculum and obtaining a working seed. The inoculum is obtained by inoculating a liquid nutrient medium with cells of a pure yeast culture of Saccharomyces cerevisiae. Cells of pure yeast culture were obtained, for example, by special selection of Saccharomyces cerevisiae, for example, a special strain of Saccharomyces vini. VKPM U-511.

Table 1 shows the dynamics of the growth of yeast in liquid nutrient media. It can be seen from it that the most optimal combination of the cultivation duration and the value of exponential growth, during which the optimal number of microorganisms is achieved, is the ratio per 1 g of the nutrient medium to 7 wt.% Bran, for example, of any grain crops, including wheat and / or rye. Moreover, this ratio is approximately the same for native bran and extruded.

The dependence of the productivity of yeast on the solid phase on the composition of the nutrient medium for producing seed is shown in Table 5. The dependence of the productivity of yeast on the volume of liquid added per 1 kg of the mixture of dry bran is shown in Table 3. The revealed patterns made it possible to determine two main modes of microorganism cultivation for producing the inoculum: the first - with a cultivation duration of not more than 30 hours at a temperature of 28-30 ° C, and the second - with a duration of up to 24 hours, when 7 wt. .% extruded bran of cereals, such as wheat bran. Table 2 shows that at 48 hours of cultivation, the optimal ratio of dead and living cells is not obtained, which on the carrier provides exponential cell growth to obtain the final product. In the period after 30 hours, as shown in the table, there is no increase in the number of microbial bodies in the final product, and hence the biomass as a whole, its maximum value does not occur or is not reached, since secondary factors begin to act, for example, the number of dead bodies in the seed material that cannot continue to produce biomass on a carrier. In both cases, when preparing the seed, the required concentration of yeast cells is achieved by adding 1 · 10 ⁵ cells / ml of liquid nutrient medium. However, the introduction of extruded bran significantly saves time for cultivation, provided that there is sufficient nutrition for microorganisms, because cell proliferation quickly passes into the stage of exponential growth due to the increased contaminating surface of the carrier. Upon receipt of the preliminary seed material, a solid medium can be used first, for example, growing on an agar-agar mattress and then flushing the biomass to obtain a liquid seed in the form of an onoculum.

Cultivation of the working inoculum up to 1 · 10 ⁵ cells / ml is also carried out after the inoculum is introduced in a proportion of 1 to 10 by volume to the liquid nutrient medium, both in the case of the addition of extruded bran and without it. However, if extruded bran is added, the cultivation time is 24 hours, i.e. significantly less than 30 hours without the addition of extruded bran, while the concentration of seed cells is achieved at least 1 · 10 ⁸ cells / ml The data of these experiments are shown in table 4, showing the choice of dilution of the inoculum with a stepwise receipt of seed depending on the composition of the medium, see table 3.

Getting the final product, i.e. the implementation of solid-phase fermentation is carried out on the composition of the solid medium in the proportions: for example, wheat bran extruded 70-75%, for example, native wheat bran 25-30%, drinking water 1.2-1.4 l / kg bran mixture. Sowing is done with working seed at the rate of 20 · 10 ⁹ -40 · 10 ⁹ cells / g of dry product. The starting mixture is obtained for solid phase fermentation, which is performed for 16-18 hours at a temperature of 28-30 ° C and a humidity of 90-100% until a yeast cell concentration (Saccharomyces cerevisiae) of at least 1 · 10 ⁹ cells / g is obtained source (dry) product. In this case, it is possible to obtain a concentration of up to 1 · 10 ¹² / g of the initial (dry) product, if you do not stop as needed, based on the desired beneficial effect, the duration of the exponential growth of microorganisms, as well as subject to a sufficient amount of nutrients and contaminating surface for microbial growth bodies and their functioning (processing of trace elements in the form of metabolites of their activity). The required number of microbial bodies in the biomass of the final product can also be obtained by increasing the concentration of the introduced seed material, however, if the conditions of nutrition and the amount of contaminating surface for each microorganism (specific contaminating surface) are met, see table 5. Thus, the technical result is achieved , i.e. the increase in the contaminating surface of the carrier of microorganisms to significantly increase the biomass of microbial bodies (microorganisms) and the number of microbial bodies per unit volume of the carrier.

Drying and inactivation to obtain the target product is carried out simultaneously in the installation, the principle of which is based on a combined radiation-convective method of drying products using the properties of infrared radiation at an infrared radiation density of (0.1-2.0) W / cm ² with a wavelength ( 4.3-8.2) microns. This method of drying and inactivation allows you to destroy the harmful microflora, preserve vitamins, biologically active substances (at the level of 80-90% of the feedstock), natural color and aroma in the product. This ensures an increase in biomass due to an increase in the number of microbial bodies of microorganisms per unit volume of the target product while increasing the absorption capacity of the target product and improving the environmental friendliness of the target product, its bioavailability. It is possible to prepare source material for the carrier also by the method of vibration-plastic processing of bran of cereal crops.

Biologically active food supplement of prebiotic action, leading to correction (leveling) of metabolic syndrome

The invention relates to microbiology and relates to a method for producing a preparation of the Eubicor type. The Eubicor class of drugs is a biologically active food or feed additive (BAA), which is a combination of biologically active substances containing biotransformed organic and inorganic substances. The main biologically active substance (BAS) is the inactivated microorganisms of the Saccharomycetaceae family, cultivated in a specially prepared nutrient medium and forming biomass immobilized on an edible carrier. The scope is both the food industry and the production of feed products.

It is known "A tool with eubiotic properties" (RU, patent 2020932, publ. 15.10.94, bull. No. 19), which contains biomass containing microbial bodies 1 · 10 ⁹ per 1 g of the product, the biomass is immobilized on a carrier. Live microorganisms are used that have an antagonistic effect against pathogenic flora, but they do not contribute to the growth of their own beneficial intestinal flora. In addition, microbes alien to the body are used. At the same time, when the product is introduced into the body, it is necessary to protect bacteria from the effects of gastric juice, for which protectors are introduced - stabilizing additives that block the adhesion of beneficial microbial bodies and prevent their colonization in the intestine and bioavailability.

The well-known "Method for the production of therapeutic and prophylactic food additives" (RU, patent 2102903, publ. 01/27/98, bull. No. 3), allowing to obtain a biologically active food supplement using microorganisms Saccharomyces cerevisiae (vini) VKPM U-511, cultivated on vegetable or milk raw materials. Supplements have the ability to neutralize toxic metabolites. However, with this method of cultivation, a qualitatively new effect is not achieved on the endogenous flora of the intestine, for example, there is no ability to significantly increase the contaminating surface for the intestinal flora, and therefore there is no ability to stimulate the growth of the endogenous flora, which has the property of correcting the metabolic syndrome. In addition, the insufficient environmental friendliness of the product, since it is necessary to fight against the growth of bacteria from an extraneous medium, and the insufficient adsorption capacity, since sterile raw materials have to be used, significantly reduces the inhibitory effect on the growth of extraneous microbial flora.

The well-known "Method for the production of a probiotic for animal husbandry, mainly poultry farming" (RU, patent 2000116, publ. 07.09.93, bull. No. 33-36), which allows to obtain a probiotic for the formation and stabilization of intestinal microbiocenosis, consisting of a mixture of dry monocultures. However, it is intended for animals whose digestive tract has its own physiological characteristics compared to the human body. In addition, a probiotic acts as the final product.

The closest in technical essence is the invention "Preventive preparation Subarin" (RU, patent 2035185, publ. 05.20.95, bull. No. 14), containing biomass, filler with the number of microbial bodies 1 · 10 ⁹ -1 · 10 ¹⁰ / ml The drug is used to prevent dysbiosis. However, live microorganisms are used, which have high antagonistic activity in relation to the spectrum of pathogenic and conditionally pathogenic microorganisms in the body due to alien introduced from outside microorganisms, and do not activate the growth of the body’s own endogenous flora, which will be the most environmentally friendly effect against pathogenic microbes.

Currently, there is a need to create a biologically active food supplement (BAA), which is a composition of biologically active substances (BAS) that interacts through the endogenous regulation system of the body with target cells and organs, thereby exogenously regulating their functional activity. [V.A. Tutelian, "Strategy for the development, application and evaluation of the effect of biologically active food additives", M, 1996, p.10]. Due to its effect on the endogenous intestinal flora (prebiotic bifidobacteria and lactogenic effects), correction (leveling) of the main manifestations of the metabolic syndrome, in particular dyslipoproteinemia of an atherogenic profile, can be carried out.

Types of biologically active food additives are: nutraceuticals - substances for correcting the chemical composition of the nutrient medium (food) for the intestinal flora, for additional sources of nutrients to the human body, i.e. vitamins, proteins, fats, carbohydrates, minerals, dietary fiber; eubiotics - dietary supplements, the composition of which includes living or dead microorganisms and / or their metabolites, which have a normalizing effect on the composition and biological activity of the microflora of the digestive tract. (MUK 2.3.721-98 "Determination of the safety and effectiveness of biologically active food additives", M., 1999, p. 5, 6). Moreover, in accordance with the definition of MUK 2.3.721-98, probiotics that contain live microorganisms and prebiotics that contain dead (inactivated) microorganisms belong to eubiotics. In accordance with the definition of the authors: Shenderov V.A., Manvelova M.A. "Functional nutrition and probiotics: microecological aspects.", From. M., Agar, 1997, p.24, the probiotics include "living and dead organisms existing in the human intestine, and prebiotics include the vital products of microorganisms, as well as normal dead microorganisms that are absent in the human body." The proposed dietary supplement relates to prebiotics.

All types of dietary supplements have more or less dietary properties, i.e. the ability to increase the digestibility of the target product, i.e. its bioavailability, reducing the traumatic effect of coarse bran fibers (mucous membrane) of the sensitive mucosa of the surfaces of the gastrointestinal tract. At the same time, prebiotics are the most environmentally friendly, because they stimulate the growth of their own intestinal flora without introducing alien living microorganisms that may turn out to be pathogens with respect to the endogenous flora. At the same time, the target product is understood to be the source of microelements, which is replenished either due to substances received by the body from the outside (exogenous effects), for example, food products, or due to microelements produced by microorganisms of the intestine (endogenous function).

The target product consists of biomass and a carrier. Biomass consists of microelements and microbial bodies (microorganisms), which upon inactivation are cell bodies with a changed structure. Chemicals with a structure changed by microorganisms have a milder effect than microelements obtained by anthropogenic means. Biomass cell bodies are living or dead microorganisms (microbial bodies), such as yeast (Saccharomycetaeceae), its advantage is that they are absolutely harmless, which is proved by their use in the baking industry and winemaking, which are the producer of trace elements. In turn, micronutrients are understood as organic and inorganic substances synthesized and / or biotransformed by microorganisms and having a biotransformed form (in contrast to chemical compounds of anthropogenic form).

The objective of the invention is to obtain a new composition of natural biologically active substances with the most optimal ratio and structure of biomass and carrier, which can purposefully affect the endogenous intestinal flora, for example, increase the contaminating surface for the endogenous intestinal flora, as well as stimulate the growth of the endogenous intestinal flora. At the same time, the sorption effect and dietary properties of the target product and the bioavailability of food additives, dietary supplements in the intestine increase, as a result of which the metabolic syndrome is corrected by connecting the body’s own reserves, for example, stimulating the growth of the body’s own microflora.

The problem is solved by creating a biologically active food supplement with a prebiotic effect that increases the representation of the main bifido and lactogenic flora for the correction (leveling) of the main manifestations of the metabolic syndrome, in particular dyslipopreidemia of an atherogenic profile.

Dietary supplement (BAA) for food of a prebiotic action, leading to the correction of the metabolic syndrome, consisting of Saccharomyces biomass immobilized on bran crops containing biotransformed organic substances represented by carbohydrates, proteins, fats, vitamins, dietary fiber and inorganic substances, characterized in that contains bran of crops, some of which are the remains of the cytoskeleton of cell membranes of crops formed as a result of disintegration to etochnyh membrane during, for example, extrusion, and have a mesh, a porous surface is not less than 2.0 m ² / g, and the content of soluble fiber increased by more than 1.0 vol.% and the insoluble fiber is reduced by more than 3.0 vol.% due to the reduction of hemicellulose by 3.0 vol.% and cellulose by 1.9 vol.%, moreover, the dietary supplement has the structure of fine particles with a size of not more than 2 mm, and the biomass is a Saccharomyces cytoskeleton with a concentration of at least 10 ⁹ -10 ¹² cells / g of 1, wherein the biotransforming organic substance constitute not less than 80-90 wt.% of aces bran cereal, the balance being biotransforming inorganics. A biologically active additive (BAA) to food containing wheat bran and / or rye is possible. Possible dietary supplement based on Saccharomyces, presented by Saccharomyces cerevisiae (vini) VKPM U-511. Supplements to food with the disintegration of cell membranes by vibrational grinding of bran cereal crops are possible. Food supplements containing wheat bran and / or rye are possible.

The proposed invention is implemented as follows. A biologically active food supplement with a prebiotic effect, leading to the correction (leveling) of the metabolic syndrome, consists of biomass immobilized on a filler (carrier), where the filler is a carrier of microbial bodies, which is used as bran of cereal crops, for example, wheat bran, which are processed in such a way that they are the remains of the cytoskeleton of the cell membranes of cereals formed from the disintegration of cell membranes during extrusion vials, and have a cellular, porous surface (S) for microbial contamination of 2.0 m ² / g of carrier. The surface of the dietary supplement carrier populated by microorganisms with respect to the un populated surface is observed in a ratio that provides an effective amount of free contamination surface for its colonization by the body's own beneficial microorganisms (microflora) (endogenous intestinal flora) with respect to the inactivated microorganisms of the Saccharomycetaeceae family.

For example, Saccharomyces, for example, Saccharomyces cerevisiae (vini), were taken as microbial bodies, and for the disintegration, both the method of extruding the filler (bran) and vibrational grinding of the filler - bran of cereal crops can be used. Food supplements of the Eubicor type have fine particles with a size of not more than 2.0 mm, where the content of soluble fiber is increased compared to the filler, which is a native bran by more than 1.0% by volume of the filler, and insoluble fiber is reduced by more than by 3.0% due to a decrease in hemicellulose by 3.0% and cellulose by 1.9%.

Biomass is a mass consisting of fragments of the cytoskeleton of the cell bodies of microorganisms, where, for example, Saccharomyces cerevisiae (vini) with the number of microbial cells per 1 g of dietary supplement mass of at least 10 ⁹ -10 ¹² cells and including organic and inorganic substances, were taken as microorganisms biotransformed by microorganisms, namely organic products of their vital activity, containing carbohydrates, proteins, fats, vitamins, dietary fiber in a proportion of 80-90 wt.% from the level of the filler feedstock and minerals - the rest. Extruded bran has an absorption capacity, i.e. the ability to absorb inorganic harmful impurities from the environment, such as the intestines, compared with native bran, for example in wheat bran, pesticides - 2 times, copper - 1.7 times, zinc - 1.3 times more. Due to the breaking of the molecular and intermolecular bonds of dietary fiber, the bonds are broken even in fiber molecules, i.e. there is a violation of ligno-carbohydrate bonds, which allows you to activate the components contained in them, including lignin, and to obtain a product with increased sorption capacity.

Each of the types of trace elements biotransformed by microorganisms, as well as substances of both biological origin and mineral, for example, the cytoskeleton of yeast cells, fragments of disintegrated plant cells, are biologically active substances that form a new combination of them.

The obtained dietary supplement for food of the Eubikor type allows using the obtained new composition of natural biologically active substances with the most optimal ratio and structure of biomass and carrier to provide a targeted effect on the endogenous intestinal flora. This effect, in particular, is achieved by increasing the contaminating surface for the endogenous intestinal flora, which stimulates the growth of the endogenous intestinal flora of a person or animal, and at the same time, the sorption effect and dietary properties of the target product (dietary supplement for dietary supplements) increase upon the spread of its own beneficial microflora intestines. In addition, during the extrusion of bran of grain crops, as a result of powerful mechanical and thermal effects, the macromolecules of dietary fiber are split into smaller fragments; intermolecular and intramolecular chemical bonds break, so the chemical and physical properties of the fibers change significantly. The bonds are broken even in the molecules of fiber, which leads to an increase in the proportion of its soluble part up to 15%.

Thus, the obtained new BAA composition with an optimal ratio of biomass and filler due to the increase in the contaminating surface of BAA for the endogenous intestinal flora provides exogenous regulation of the functional activity of cells and organs, increases the sorption effect, and increases the dietary properties of BAA to food.

The drawing shows a graph of the ratio of the integral indicators of the effects of the new dietary supplement to food, which provides exogenous regulation of the functional activity of cells and organs of healthy people in comparison with the integral indicators of healthy people who do not take Eubicor type dietary supplements - working title Rekitsen - RD.

The resulting dietary supplement based on extruded bran of cereals, for example wheat and / or rye, is disintegrated, i.e. destroyed cell membranes, which is achieved due to microexplosion of the cells of plant materials due to pressure drop during a sharp impact on them with pressure up to 100 kg / cm ² at a high temperature above (120-170) ° С. Fermented Saccharomyces cerevisiae (vini) and inactivated target product provide the introduction into the body of useful trace elements, which are biologically active substances and porous, with a large contaminating surface of the filler. The fact that the specially fermented target product of the Eubicor type contains the remains of cells of a specially selected unique strain of wine yeast - Saccharomyces vini, sorbed according to the original technology to extruded wheat bran, makes it possible to achieve the optimal ratio of the filler surface populated with non-microorganisms. This makes it possible to activate the growth of their own beneficial intestinal microorganisms, which provide an additional surface for their resettlement. In addition, the structure of the soluble and insoluble filler fibers themselves is a good absorbent for poisons in the intestine, which gives the sorption properties of the resulting dietary supplement. In addition, soluble fiber is present in an amount effective for the manifestation of dietary properties of dietary supplements. Thus, dietary supplement is a diet and a reservoir of its own beneficial intestinal flora at the same time, which sharply stimulates the main endogenous bifidobacteria and lacto-flora and helps to level the main manifestations of the metabolic syndrome, in particular dyslipoproteinemia of atherogenic profile. Due to changes in the structure of bran and an increase in the amount of biomass of yeast cells, the sorption capacity of the drug increases. By creating a fine dispersion of the carrier, the damaging effect of the native bran on the inflamed, eroded and expressed mucous surface of the gastrointestinal tract is eliminated. Thanks to the above qualities, the selective action of dietary supplements is ensured.

As a characteristic confirming the achievement of the effect of exogenous regulation of the functional activity of cells and organs and an increase in the sorption effect, as well as an increase in the dietary properties and bioavailability of dietary supplements to food, a characteristic of average indicators of fatigue depending on the time of exposure to adverse climatic conditions is presented.

For example, a study of the influence of dietary supplements of the Eubikor type on the functional state of the mechanisms of adaptation processes in healthy individuals was carried out in Antarctica at the Progress and Novolazorevskoye bases for 9 months. In this case, body mass indices, the frequency and nature of the stool, vegetative index, psychophysiological indicators, quality of life, etc. were evaluated. The results of the studies showed that with the use of dietary supplements of the Eubikor type, the maladaptation period passes significantly faster (within the first 1-4 months) compared with the control group who did not take eubicor (7-8 months), due to the correction of the metabolic syndrome that develops in people working in adverse conditions of the Far North. Analysis of indicators (in points) of well-being, self-assessment of activity, mood, working capacity and sleep revealed that in the control group they were more often reduced, while fatigue increased. At the same time, in the group additionally receiving dietary supplements of the Eubicor type, a decrease in fatigue, an increase in working capacity, and an improvement in appetite were revealed. Also, throughout the entire observation period, persons who additionally received dietary supplements of the Eubicor type were questioned by the questionnaire-survey method about the influence of dietary supplements on reducing fatigue, increasing working capacity, improving appetite, and improving stool regulation. The high proportion of patients in the group who answered in the affirmative to the above and similar questions also confirmed its high efficiency in correcting intestinal disorders (dysfunctions) due to the presence of metabolic syndrome and the possibility of using dietary supplements as a means of stimulating adaptation processes and normalizing metabolic intestinal syndrome . The achieved effect proves the presence of a targeted effect on the endogenous intestinal flora, for example, an increase through the contaminating surface for the endogenous intestinal flora, stimulation of the growth of the endogenous intestinal flora and, in turn, correction of the metabolic syndrome.

Thus, dietary supplements for this type of food expand the range of indications for use, have improved taste, allow you to reduce the dose of its use, are environmentally friendly and easily bioavailable product. Moreover, the dose of the drug is reduced due to an increase in its activity.

A drug for the regulation of microbiocenosis of the gastrointestinal tract

The invention relates to the pharmaceutical industry and medicine. The drug is obtained on the basis of microbiological methods and relates to drugs obtained on the basis of a class of drugs such as Eubicor. The drug is used in medicine and veterinary medicine.

The Eubicor class of drugs is basically a biologically active additive, the main component of which is the inactivated microorganisms of the Saccharomycetaceae family, cultivated in a specially prepared nutrient medium and forming a biomass placed on a carrier.

Known "A method of obtaining a preparation containing a factor (G - CSF), stimulating the growth of granulocyte colonies (RU, patent 2025120, 30.12.94, bull. No. 24), providing a preparation containing a substance selected from the group of pharmaceutically acceptable surfactant , saccharide and protein. It gives the growth effect in the body of beneficial microflora. However, it solves another problem, namely increasing the stability of this drug in the body.

It is known "A tool with eubiotic properties" (RU, patent 2020932, publ. 15.10.94, bull. No. 19), which contains biomass containing microbial bodies 1 · 10 ⁹ per 1 g of the product, the biomass is immobilized on a carrier. Live microorganisms are used that have an antagonistic effect against pathogenic flora. However, the biomass is immobilized on calcium analget - an inorganic substance and does not participate in the process of correcting colonization in the intestines of beneficial flora, since it solves problems other than those stated in the invention.

The well-known "drug that affects tissue metabolism and the use of the strain of the fungus Fusarium Sambucinum Fuckel var Ossicolum (berk / et curf) Bilai for its production", with adaptogenic and immunomodulatory effects. In this preparation, a strain is used as a producer of physiologically active substances of prophylactic and therapeutic purposes. However, it is only combined with traditional therapeutic agents when conducting rigorous treatment methods. As an independent drug, the spectrum of its physiological effects is very limited.

Closest to the claimed technical solution is "A preparation containing a biologically active agent" (RU, patent 2041715, publ. 07/20/95, bull. No. 23), containing biologically active substances based on modified (biotransformed) ingredients of biological tissue and filler. The drug provides such an effect on the body, in which the parameters of the physiological state are normalized. However, the drug uses ingredients from animal tissue, which is not environmentally friendly.

A medicinal product refers to substances intended for therapy and support within the physiological boundaries of the functional activity of human organs and systems through an increase in the bifid, lacto, coligenic effect of stimulants of the target product.

Upon receipt of a new composition of natural biologically active substances with the most optimal ratio of biomass and carrier, which can purposefully affect the endogenous intestinal flora, for example, increase the contaminating surface for the intestinal flora, stimulate the growth of the endogenous flora, it is possible to regulate the amount of biotransformed inorganic chemical compounds, for example, potassium, magnesium , calcium, phosphorus. In addition, an increase in the sorption effect, dietary properties of the target product and its bioavailability makes it possible to obtain a medicinal product, a pharmacological agent of prebiotic action, which has a pronounced bifido-, lacto-, coligenic effect and possesses water absorption and swelling properties, as well as sorption properties.

The drug carries out a targeted change in the endogenous intestinal flora by increasing the representation of the bifidobacteria and lactogenic intestinal flora, which is used to obtain a therapeutic effect, which results in correction and treatment of the metabolic syndrome (synonyms - cardiovascular syndrome, X syndrome, deadly quartet, syxtet, quintet). The treatment of diseases of the digestive system, endocrine system, cardiovascular system, skin diseases, acute and chronic infectious diseases is also carried out through targeted exposure (correction) to intestinal microbiocenosis. However, through a directed effect on the intestinal microbiocenosis, private positive effects, for example, immunomodulation, are realized.

To solve this problem, a drug of preoyotic action is proposed. A drug for the regulation of gastrointestinal microbiocenosis, consisting of dietary supplements, which are components of Saccharomyces cerevisiae (vini) cells immobilized on a porous carrier of plant origin, and containing biotransformed organic substances represented by carbohydrates, proteins, fats, vitamins, dietary fiber and inorganic substances represented by compounds of macroelements of potassium, magnesium, sodium, calcium, phosphorus, characterized in that the organic and inorganic substances contain zhatsya in effective amounts, while the components of Saccharomyces cerevisiae (vini) cells are a cell cytoskeleton obtained after inactivation of Saccharomyces cerevisiae (vini) combined radiation-convection method at a density of 0.1-2.0 W / cm ² of infrared radiation with a wavelength of 4 , 3-8.2 μm with a concentration of 10 ⁹ -10 ¹² cells / g, the porous carrier of plant origin has a specific surface area of at least 0.4 m ² / g, the target product has a surface of at least 2.0 m ² / g and contains , wt.%:

Lipids 2-5

Carbohydrates 25-50

Proteins, vitamins, macronutrients and dietary fiber

while proteins include ten essential amino acids in an amount of 30.0-75.0 wt.% of the amount of proteins, vitamins include at least wt.%:

B ₁ 2.9-4.2

B ₂ 9.0-11.3

B ₃ 11.1-15.0

B ₆ 2.5-5.1

PP 11.0-15.2

C 16.5-17.2;

Macronutrients include at least wt.%:

Phosphorus 1.5-1.8

Potassium 1.6-2.2

Sodium 0.9-1.1

Magnesium At least 1.3

Calcium Not less than 0.16

and dietary fiber include, wt.%:

Soluble dietary fiber Not less than 45

Insoluble dietary fiber At least 35.

In the Saccharomyces drug, Saccharomyces cerevisiae (vini) VKPM U-511 may be presented. In a medicament, the porous carrier of plant origin may be wheat bran and / or rye extruded.

A medicinal product includes, for example, fats, including, wt.%:

Triglycerides 26.4-27.2

Esters of sterols 20-25%

sterols Else,

moreover, beta-sitosterol 58-64% of the total sterols.

The drug includes proteins, wt.%:

Lysine Under 3.7

Valin Up to 2.8

Isoleucine Up to 2.3

Phenylalanine Under 2.1

The proposed drug for the regulation of microbiocenosis of the gastrointestinal tract shows its properties due to the following components: due to the content of biologically active additives (BAA), filler and cell components in% of dry biomass and the content of, for example, lipids 2-5%, of which triglycerides 26.4-27.2%, sterol esters 20-25%, beta-sitosterol 58-64% of the total sterols; proteins, including 10 essential amino acids 30.0-75.0%, of which lysine up to 3.7% of the total amino acid composition of the protein, valine up to 2.8%, isoleucine up to 2.3%, phenylalanine up to 2.1 %, carbohydrates 25-50%, vitamins, mg%: B ₁ 2,9-4,2; B ₂ 9.0-11.3; B ₃ 11.1-15.0, B ₆ 2.5-5.1; PP 11.0-15.2; C 16.5-17.2; macronutrients, in% of dry biomass: phosphorus 1.5-1.8%, potassium 1.6-2.2%, sodium 0.9-1.1%, magnesium at least 1.3%, calcium at least 0 ,16%.

The drug contains a biologically active additive (BAA), which is obtained on the basis of biomass, including the vital products of cells of a strain of the Saccharomyces cerevisiae strain, produced in the form of organic and inorganic substances consisting of biotransformed microorganisms of proteins, vitamins, lipids, carbohydrates, dietary fiber and / or biotransformed by microorganisms potassium, magnesium, sodium, calcium, phosphorus. Moreover, organic and inorganic substances were obtained in effective amounts, and inactivated cells of the actual strain of the Saccharomyces cerevisiae strain, including cell components in the form of the Saccharomyces cerevisiae cytoskeleton, obtained by exposure to living Saccharomyces cerevisiae cells upon inactivation by thermoplastic exposure with parameters: infrared radiation density (0 , 1-2,0) W / cm ² with a wavelength (4,3-8,2) microns, and the filler in the form of a porous, hygroscopic adsorbent of vegetable origin with a specific surface area of not less than 2.0 ² / g filler having a specific ratio of Saccharomyces cerevisiae cells per unit weight of the filler is not less than 10 ^{9 to} 10 ^12, wherein the ratio of filler and biomass taken into effective for deliberate action on the intestinal microbiocenosis amounts.

For example, a medicinal product contains a dietary supplement, an excipient, and cell components, where a biomass based on biomass, including the vital products of cells of a strain of the Saccharomyces cerevisiae strain, for example Saccharomyces vini, VKPM U-511, is produced in the form of organic and inorganic substances consisting of biotransformed microorganisms proteins, vitamins, lipids, carbohydrates, dietary fiber and / or biotransformed by microorganisms potassium, magnesium, sodium, calcium, phosphorus, obtained in effective amounts, and inactivated the cells of a strain of a strain of the Saccharomyces cerevisiae strain itself, for example, Saccharomyces vini VKPM U-511. Including the cell components in the form of the cytoskeleton of Saccharomyces cerevisiae, for example, Saccharomyces vini, VKPM U-511, obtained by exposure to living cells of Saccharomyces cerevisiae during inactivation by thermoplastic exposure, in particular thermoplastic heating with parameters: infrared radiation density (0.1- 2.0) W / cm ² with a wavelength of (4.3-8.2) microns and a filler in the form of a porous, hygroscopic adsorbent of plant origin with a specific surface area of at least 0.4 m ^{2 of} filler, for example, extruded wheat bran having a specific the ratio of Saccharomyces cerevisiae cells, for example, Saccharomyces vini VKPM U-511, per unit mass of filler is not less than 10 ⁹ -10 ¹² cells / g, and the ratio of filler and biomass is taken in effective amounts for targeted action on intestinal microbiocenosis. Contains dietary fiber: soluble at least 45%, insoluble - at least 35%.

The technical result is achieved, which consists in obtaining a medicinal product, a pharmacological agent of prebiotic action, which has a pronounced bifido-, lacto-, coligenic effect and has the properties of water absorption and swelling, as well as sorption properties.

The tables show indicators characterizing the pronounced therapeutic effect of this drug.

Table 6. Coprogram indicators in patients with irritable bowel syndrome receiving eubicor (n = 97).

Table 7. The results of a study of feces for dysbiosis in patients with irritable bowel syndrome receiving eubicor (n = 97).

Table 8. "Functional and structural state of the hepatobiliary system in patients with chronic cholecystitis and biliary dyskinesia treated with Eubicor, according to ultrasound (n = 81)"

Table 9. Changes in the biochemical composition of gallbladder bile in patients with chronic cholecystitis and biliary dyskinesia treated with eubicor (n = 81).

Table 10. Changes in blood biochemical parameters in patients with chronic hepatitis and hepatoses receiving eubicor (n = 52) "

Table 11. "The dynamics of the average content of some indicators of immunological status in patients with chronic hepatitis and hepatosis receiving eubicor (n = 52).

Table 12. The dynamics of the concentration in the blood plasma of pancreatic enzymes in patients with chronic pancreatitis before and after the use of eubicore.

Table 13. The dynamics of the average content of serum and glucose lipoproteins in patients with peptic ulcer who received complex triplex or quadratherapy supplemented with eubicor (M ± m).

Table 14. The dynamics of the average content of catalase and superoxide dismutase (SOD) of erythrocytes in patients with peptic ulcer in addition to the main treatment, who received eubicor (M ± m).

Table 15. Dynamics of indicators of the mechanical properties of red blood cells in patients with peptic ulcer disease with a relapse of the disease who received eubicor.

The possibility of obtaining this drug is ensured by the application of the method of its production using extruding the starting material of the filler in accordance with the presented method for producing a biologically active drug and confirming the possibility of implementing a medicinal product with the declared properties.

The properties of the drug are confirmed by the type of activity of the drug, which stimulates the bifido-, lacto-, coligenic effect in the gastrointestinal tract and has the properties of water absorption and swelling, as well as sorption properties that are manifested in the human body. This is confirmed by clinical studies during the year 2000 at the Department and Clinic for Gastroenterology of the Military Medical Academy and its clinical bases (Department of Gastroenterology, Hospital of the Holy Great Martyr Elizabeth, medical unit No. 7), where the clinical effectiveness of a biologically active pharmacological agent of the Eubicor type was evaluated ", for example Rekitsen - RD. Evaluation of the effectiveness of this drug was carried out according to the methodology of the professor of the Russian Military Medical Academy VB Grinevich, which includes a method for evaluating the effectiveness of the therapeutic effect on the human body, claimed as an application for invention No. PCT / RU 97/00224.

A distinctive feature of drugs of the prebiotic class (lactulose, retsen-RD), such as eubiotics, is their pronounced bifidobacteria and lactogenic effect, as a result of which the optimal composition of the intestinal microflora is restored.

The importance of correcting dysbiotic disorders, which are often present in various forms of pathology in the clinic of internal diseases, is dictated by the fact that the microbiocenotic composition of the intestinal flora plays a significant role in the regulation of basic metabolic functions (the state of lipid, carbohydrate homeostasis, the formation of an antioxidant defense system that inhibits peroxidation processes cell membrane modifications).

Eubicor was prescribed to patients with the following diseases:

- irritable bowel syndrome - 97 patients;

- chronic cholecystitis - 42;

- biliary dyskinesia - 39;

- chronic pancreatitis - 32;

- alcoholic fatty hepatosis II-IV Art. - 25;

- chronic hepatitis of alcoholic and toxic origin - 27;

- peptic ulcer disease - 122, including associated with invasion of the gastric mucosa Helicobacter pylori against the background of complex eradication triplex and quadrite therapy - 86.

The duration of treatment was at least 4 weeks, the dosage of 1 teaspoon 3 times a day.

In patients receiving eubicor, the following indicators were studied in dynamics:

- general clinical;

- biochemical (AST.ALT, bilirubin, alkaline phosphatase, GGTP, amylase, glucose, potassium);

- serum cholesterol and lipoproteins (total cholesterol, LDL cholesterol, HDL cholesterol, atherogenic coefficient (KA);

- parameters of lipid peroxidation (catalase, superoxide dismutase (SOD));

- relaxation properties of erythrocytes;

- biochemical composition of bile;

- feces on the coprogram and dysbiosis;

- immunological status.

The clinical effects of eubicor in the treatment of gastroenterological diseases were confirmed by the following observations:

It was established that during the treatment of irritable bowel syndrome with eubicore, manifestations of intestinal dyspepsia regressed significantly faster: there was a decrease or disappearance of bloating and rumbling in the intestine, normal consistency and stool frequency were restored. Data from a coprological analysis and a study of feces for dysbiosis in patients with irritable bowel syndrome receiving eubicor are presented in tables 6 and 7.

As follows from the data presented, in patients receiving eubicor, amylo- and creatorrhea phenomena regress in the coprogram; in the study of feces for dysbacteriosis, positive changes in the microbial landscape are noted: the representation of the main intestinal microflora (bifidum and lactobacilli), full-fledged E. coli increases, yeast-like fungi disappear, and the content of conditionally pathogenic microorganisms decreases.

It is important to note the pronounced positive effect of eubicore, not only for the treatment of diarrheal, but also constipation syndrome in patients with irritable bowel syndrome. This action is mediated both by the restoration of intestinal microbiocenosis due to the bifidobacteria and lactogenic effects, and by the presence of extruded wheat bran with pronounced water absorption and swelling properties in the composition of this agent.

Among other positive effects achieved while taking eubicore, it is worth highlighting such as a decrease or disappearance of the astheno-vegetative syndrome, improved appetite, the disappearance of nausea, an unpleasant aftertaste in the mouth. In the treatment of patients with chronic cholecystitis and biliary dyskinesia, a significant positive clinical efficacy of eubicor was also noted (see table. 8 at the end of the description).

As follows from the data in Table 8, the parameters characterizing the motor-evacuation function of the biliary system undergo the greatest changes: the severity of signs of gallbladder dyskinesia, the heterogeneity of its contents decrease, the contractile function of the gall bladder is activated, as evidenced by a decrease in its size, and improvement of the passage of bile due to relaxation common bile duct. Noteworthy is a decrease in the size of the left lobe of the liver, possibly due to the regression of reactive changes in the organ. As a significant positive phenomenon, a decrease in the cholesterol content in the bile of patients receiving eubicor should be regarded, which indicates a decrease in the lithogenic properties of bile and the risk of cholelithiasis (Table 9).

A study of blood biochemical parameters in patients with chronic hepatitis of alcoholic and toxic genesis and hepatosis (Table 10) revealed a partial or complete regression of cytolytic and cholestatic syndromes (decreased activity or normalization of ACT, ALT, bilirubin, alkaline phosphatase, GGTP levels).

An analysis of the dynamics of immunological parameters in these patients (Table 11, at the end of the description) revealed a decrease in the level of CEC, a tendency to restore the normal helper-suppressor ratio of T-lymphocytes, which indicated a decrease in the severity of manifestations of cidrome immune inflammation.

During treatment with eubicor in patients with chronic pancreatitis, including in combination with chronic cholecystitis, a decrease in the size of the head, body and tail of the pancreas was noted (Table 8). Changes in the enzyme-forming function of the pancreas in patients with chronic pancreatitis receiving eubicor are presented in table 12.

As follows from the data presented in table 12, the levels of trypsin, trypsin inhibitor, amylase and serum lipase undergo significant changes in patients receiving eubicor. Moreover, in the initial indicators, the severity of the phenomenon of enzyme avoidance is maximum and naturally decreases as the prebiotic is taken. Amylase is the most sensitive enzyme, while the range of variation in serum lipase levels is very small.

In addition to patients with irritable bowel syndrome, diseases of the hepatobiliary system and chronic pancreatitis, eubicor was prescribed to patients with peptic ulcer.

It was found that in patients with peptic ulcer disease, combined with coronary heart disease and hypertension, who did not receive eubicor, during treatment, the content of cholesterol, triglycerides and glucose increases, whereas against the background of taking eubicor in these patients who received combined anti-ulcer therapy, which included antibacterial anti-helicobacter drugs, there was a decrease in blood glucose and cholesterol levels due to the atherogenic fraction of low density lipoproteins and triglycerides, ochetayuscheesya with increased levels of antiatherogenic high density lipoprotein fraction (Table. 13).

At the same time, an increase in the level of antioxidant enzymes of erythrocytes was noted (Table 14).

As follows from the data of table 14, in patients with peptic ulcer while taking eubicore, there is a significant increase in catalase level and a tendency to increase the activity of SOD, which suggests that this agent has an antioxidant effect, which is obviously realized through the correction of dysbiotic disorders.

The results of changes in the mechanical properties of red blood cells in patients with peptic ulcer who additionally received eubicor (Table 15) revealed a decrease in the number of red blood cells having a relatively high rigidity of plasmolema (poikilocytes, initial forms, diskotoroids), while the number of easily deformed small-stem cells, on the contrary, tended to to increase.

This result should be interpreted as definitely positive, since the presence in the blood of a large percentage of red blood cells with hard plasmolemma worsens the processes of tissue metabolism.

In patients with diseases of the digestive system, combined with the initial or drug-induced manifestations of allergies (skin itching, recurring urticaria, Quincke edema), taking eubicore is accompanied by their rapid disappearance.

When analyzing peripheral blood indices in patients receiving eubicor, an increase in hemoglobin level (by 10% on average) was achieved due to regression of sideropenic syndrome due to relief of malabsorption and improvement of iron absorption in the small intestine. A decrease in astrophase indices (regression of leukocytosis, stab shift, non-trophilic granocytes, ESR) was also revealed, indicating a decrease in the activity of inflammatory processes.

The clinical effects of eubicor in the treatment of allergic diseases were confirmed by the following observations: in patients with digestive diseases combined with the initial or drug-induced manifestations of allergies (skin itching, recurring urticaria, Quincke's edema), eubicor was accompanied by their rapid disappearance. Analysis of the dynamics of immunological parameters in these patients (table. 11) revealed a decrease in the level of CEC, a tendency to restore the normal helper-suppressor ratio of T-lymph itov, indicating a decrease in the severity of the manifestations of the syndrome of immune inflammation. The clinical effects of eubicor in the treatment of infectious diseases were confirmed by the following observations: the use of the drug in patients with acute enterocolitis was accompanied by an antidiarrheal effect, a decrease in the loss of fluid and electrolytes, restoration of the integrity of the mucous barrier and glycocalyx of enterocytes, realized through the binding of excess fluid, toxins and bacterial agents in the intestinal lumen, which was reflected in the normalization of immunological parameters characterizing the course of inflammation integral reaction (table. 11).

Thus, eubicor is a pharmacological agent with multifaceted clinical efficacy with a pronounced bifidogenesis and lactogenic effect on the intestinal microflora. As a result of increasing its protective and regulatory properties, eubicor has a regulatory and antioxidant effect, helps restore the enzymatic function of the intestine, a protective natural barrier to its mucous membrane. The pronounced sorption properties of eubicor determine its characteristic antitoxigenic, hypoglycemic and hypolipidemic effect. These positive properties of eubicore can expand the spectrum of its use in therapeutic practice for the following diseases:

- peptic ulcer against the background of complex therapy, including anti-helicobacter antibacterial drugs;

- as an enteroprotective agent in patients receiving antibiotic therapy,

- cardiovascular diseases, combined with atherogenic dyslipoproteinemia;

- allergic diseases;

- type II diabetes mellitus.

Thus, based on the obtained clinical data, it can be argued that the claimed technical result, i.e. the resulting drug has a pronounced pharmacological effect of a prebiotic nature, has a pronounced bifido-, lacto-, coligenic effect and water absorption and swelling properties, as well as sorption properties due to the increased contaminating surface of the dietary supplement carrier and the combination of dietary supplements.

If you use biomass from the target product and / or directly from the seed material with an effective ratio of the concentration of microbial bodies (and, accordingly, biologically active substances) per unit volume of the filler, this drug can be used for treatment in the form of a liquid filtrate, tablets, and also in the form of capsules with powder.

Claims (22)

1. The method of obtaining biologically active additives based on biomass Saccharomycetaeceae, which consists in preparing the nutrient medium, cultivating the seed in a nutrient medium to obtain a seed mass, placing the seed mass on bran cereals and cultivating to obtain the desired concentration of Saccharomycetaeceae cells and obtain the target product after inactivation of biomass and drying, characterized in that the seed is cultivated in a liquid nutrient medium, which is prepared by mixing density malt wort If no more than 15% with drinking water in the proportion of 50% by volume to 50% by volume is obtained, in two stages, first the preliminary sowing mass is obtained, and then the working sowing mass is obtained, and the bran of cereal crops is used as a mixture of bran of cereal crops, extruded at a pressure of up to 100 kg / cm ² and a temperature of (120-170) ° С and native with a moisture content of 10-15% with drinking water in the proportion of 1 kg of a mixture of bran of grain crops for 1.2-1.4 l of drinking water, preliminary and working seed weight was prepared in the form of an inoculum at a concentration of at least 1 × 10 ⁸ cells / ml, while both this ah in liquid nutrient medium to obtain inoculum make an initial concentration of 1 × 10 ⁵ cells / ml and cultured until the cell concentration of said further working seed weight is placed on the mixture of cereal bran in an amount of 20 · l0 ⁹ -40 · l0 ⁹ cells / kg of said mixtures and cultivated for 16-18 hours at a temperature of 28-30 ° C and a humidity of 90-100% to a concentration of at least 1 · 10 ⁹ cells / ml, and the biomass is inactivated by infrared radiation at a density of 0.1-2.0 W / cm with a wavelength of 4.3-8.2 microns simultaneously with drying, which is carried out at a temperature Ur 70-85 ° C combined radiation-convection method prior to sufficient humidity 10-15%. 2. The method according to claim 1, characterized in that the bran of cereal crops is used in proportion, wt.%: Extruded cereal bran 70-75 bran cereals native 25-30 3. The method according to claim 1, characterized in that the bran of cereal crops is used in proportion, wt.%: extruded cereal bran 50 bran cereals native 50 4. The method according to claim 1, characterized in that upon receipt of the preliminary seed mass, 7 wt.% Of extruded bran of cereal crops is added to the liquid nutrient medium and cultivated for 24 hours at a temperature of 28-30 ° C. 5. The method according to claim 1, characterized in that upon receipt of the preliminary sowing mass, cultivation is carried out for 30 hours at a temperature of 28-30 ° C. 6. The method according to claim 1, characterized in that when receiving the working seed mass, 7 wt.% Of extruded bran of cereal crops is added to the liquid nutrient medium and cultivated for 24 hours at a temperature of 28-30 ° C. 7. The method according to claim 1, characterized in that upon receipt of the working sowing mass, cultivation is carried out for 30 hours at a temperature of 28-30 ° C. 8. The method according to claim 1, characterized in that Saccharomycetaeceae are represented by Saccharomyces. 9. The method of claim 8, wherein Saccharomyces is represented by Saccharomyces cerevisiae (vini). 10. The method according to claim 1, characterized in that the use of extruded wheat bran. 11. The method according to claim 1, characterized in that the use of extruded rye bran. 12. The method according to claim 1, characterized in that the extruded bran is buckwheat. 13. Dietary supplement (BAA) for food of a prebiotic action, leading to the correction of the metabolic syndrome, consisting of biomass of Saccharomyces immobilized on bran crops containing biotransformed organic substances represented by carbohydrates, proteins, fats, vitamins, dietary fiber and inorganic substances, characterized the fact that it contains bran of cereal crops, some of which are the remains of the cytoskeleton of the cell membranes of cereals formed as a result of disintegration cell membranes during, for example, extrusion, and have a cellular, porous surface of at least 2.0 m ² / g, and the content of soluble fiber is increased by more than 1.0 vol.%, and insoluble fiber is reduced by more than 3.0 vol.% due to the reduction of hemicellulose by 3.0 vol.% and cellulose by 1.9 vol.%, moreover, the dietary supplement has the structure of fine particles with a size of not more than 2 mm, and the biomass is a Saccharomyces cytoskeleton with a concentration of at least 10 ⁹ -10 ¹² cells / 1 g, moreover, biotransformed organic matter is not less than 80-90 wt.% from the mass of bran of crops, the rest is biotransformed inorganic substances. 14. Dietary supplement (BAA) to food according to item 13, characterized in that it contains wheat bran and / or rye. 15. Biologically active food supplement (BAA) according to claim 13, characterized in that Saccharomyces are represented by Saccharomyces cerevisiae (vini) VKPM U-511. 16. Biologically active food supplement (BAA) according to claim 13, characterized in that the disintegration of cell membranes is carried out by vibrational grinding of bran of grain crops. 17. A biologically active food supplement (BAA) according to claim 16, characterized in that it contains wheat bran and / or rye bran. 18. A drug for the regulation of microbiocenosis of the gastrointestinal tract, consisting of dietary supplement for food, which is a component of Saccharomyces cerevisiae (vini) cells immobilized on a porous carrier of plant origin, and containing biotransformed organic substances represented by carbohydrates, proteins, fats, vitamins, dietary fiber and inorganic substances, represented by compounds of macroelements of potassium, magnesium, sodium, calcium, phosphorus, characterized in that organic and inorganic substances with erzhatsya in effective amounts, while the components of Saccharomyces cerevisiae (vini) cells are a cell cytoskeleton obtained after inactivation of Saccharomyces cerevisiae (vini) combined radiation-convection method at a density of 0.1-2.0 W / cm ² of infrared radiation with a wavelength of 4 , 3-8.2 μm with a concentration of 10 ⁹ -10 ¹² cells / g, the porous carrier of plant origin has a specific surface area of at least 0.4 m ² / g, the target product has a surface of at least 2.0 m ² / g and contains , wt.%: lipids 2-5 carbohydrates 25-50 proteins, vitamins, macronutrients and dietary fiber while the proteins include ten essential amino acids in an amount of 30.0-75.0 wt.% of the amount of proteins, vitamins include at least wt.%: B ₁ 2.9-4.2 B ₂ 9.0-11.3 B ₃ 11.1-15.0 B ₆ 2.5-5.1 PP 11.0-15.2 S 16.5-17.2 macronutrients include at least wt.%: phosphorus 1.5-1.8 potassium 1.6-2.2 sodium 0.9-1.1 magnesium not less than 1.3 calcium not less than 0.16 and dietary fiber include, wt.%: soluble dietary fiber not less than 45 insoluble dietary fiber not less than 35 19. The drug according to p, characterized in that Saccharomyces represented by Saccharomyces cerevisiae (vini) VKPM U-511. 20. The drug product according to p. 18, characterized in that the porous carrier of plant origin is a wheat bran and / or rye extruded. 21. The drug according to p, characterized in that the fats include, wt.%: triglycerides 26.4-27.2 sterol esters 20-25 sterols rest moreover, beta-sitosterol is 58-64 of the sum of all sterols. 22. The drug is p, characterized in that the proteins include, wt.%: lysine up to 3.7 valine up to 2.8 isoleucine up to 2.3 phenylalanine up to 2.1

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