WO2012091598A1

WO2012091598A1 - Composition for eliminating toxins from the body and for normalizing the microflora in the intestines

Info

Publication number: WO2012091598A1
Application number: PCT/RU2010/000802
Authority: WO
Inventors: Александр Владимирович ДИКОВСКИЙ; Борис Анатольевич РУДОЙ
Original assignee: Dikovskiy Aleksander Vladimirovich; Rudoy Boris Anatolievich
Priority date: 2010-12-30
Filing date: 2010-12-30
Publication date: 2012-07-05

Abstract

The invention relates to biotechnology, and to the food and pharmaceutical industries. The composition for eliminating toxins from the body and for normalizing the microflora in the intestines comprises at least one insoluble enterosorbent (insoluble edible fibre or a mineral substance), cocoa butter and a prebiotic in the form of an oligosaccharide, with the following component content: 3-50% by mass of enterosorbent, 5-60% by mass of cocoa butter and 3-50% by mass of prebiotic. The enterosorbent and the prebiotic are used in the form of a powder with a particle size of a maximum of 65 μm. The composition additionally comprises a taste additive or taste corrector, and/or an edible dye, and lecithin as an emulsifier and liquid paraffin as a diluent.

Description

Composition for cleansing the body of toxins and normalizing the intestinal microflora The technical field to which the invention relates

The invention relates to biotechnology, the food and pharmaceutical industries, and in particular to the production of functional food products for normalizing the state of the body and dietary supplements (BAA) for food, designed to remove toxic substances from the body and to normalize the composition of the microflora of the digestive tract, broken due to various diseases bacterial or chemical intoxication, including during antibiotic therapy.

State of the art

Intoxication of the human and animal organisms is a syndrome that accompanies a wide variety of pathological processes and conditions, such as poisoning by exogenous poisons or infectious diseases, or damage to internal organs and systems, accompanied by either an increased formation or a decrease in the efficiency of elimination and neutralization of endogenous (metabolic) poisons, which are often simplified as

"Slags." One of such pathological conditions is, in particular, intestinal dysbiosis, which manifests itself, in some cases, in the form of a syndrome of excessive growth of bacteria in the small intestine.

In order to prevent, reduce the severity of manifestations and normalize impaired functions of the gastrointestinal tract, various agents can be used.

In particular, a useful food product is known that helps control intestinal functions and reduces constipation (constipation), consisting mainly of a mixture of oligosaccharides that act on

Lactobacillus bifidus (such as raffinose, stachyose, fructooligosaccharides, etc.), and edible dietary fibers such as hemicellulose, lignin, pectin, and the like. (JP63063366 1988, "HEALTHY FOOD FOR PROMOTING CONTROL OF INTESTINAL FUNCTION)), A23L1 / 48; C12N1 / 38; C12R1 / 01; A23L1 / 48;

C12N1 / 38; A23L1 / 48; C12N1 / 38; C12R1 / 01)

Also known is a similar composition for normalizing bowel function, contributing to the correction of pH values of intestinal contents, reducing putrefactive processes and having a therapeutic and prophylactic effect against hepatoencephalopathy, colon diseases, intestinal cancer, the main components of which are a mixture of oligosaccharides (raffinose, stachyose, etc.) and edible dietary fiber, such as hemicellulose, pectin, etc. (JP3151854, 1991, ((COMPOSITION FOR IMPROVING INTESTINAL ENVIRONMENT)), A23L1 / 30; A23C9 / 152; A23L1 / 308; A61K31 / 70; A61K31 / 702; A61P39 / 02).

The disadvantages of both of these compositions are the fact that the main role in them is played by a mixture of oligosaccharides isolated from soybeans, which is designed to stimulate the growth of mainly certain types of lactobacilli, while many other types of lactobacilli, as well as useful bifidobacteria , enterococci are not able to utilize raffinose or stachyose, which are oligosaccharides of plant origin. In this regard, raffinosis and stachyosis by most experts are not included in the lists of true prebiotics at all (Roberfroid MB; Prebiotics: The Concept Revisited. J Nutr. 2007; 137: 830S).

A significant disadvantage of these compositions is also the fact that the insoluble dietary fiber included in the product in accordance with the description of the invention is intended only for normalizing action on the motor function of the intestine, which together with the prebiotic component only contributes to the elimination of constipation, and the therapeutic and prophylactic effect diseases of the large intestine and hepatoencephalopathy. At the same time, the indicated compositions do not declare, do not take into account, do not analyze, and do not study the enterosorption effects of dietary fiber and the contribution of such phenomena to the total effect of normalizing the functions of the gastrointestinal tract, therefore, these compositions have a limited purpose, not covering many dysfunctions gastrointestinal tract, such as, for example, infectious diseases, accompanied by serious changes in the composition and properties of the intestinal microflora. As noted above, enterosorption is one of the known methods that contribute to the elimination of pathogenic microorganisms and the toxins formed by them from the intestinal lumen, which is used in various therapeutic options for the enterosorbents themselves or their combinations with probiotics. ("Prebiotic and probiotic compositions and methods for their use in gut-based therapies" United States Patent 6706287;

Bezkorovainy A., "Probiotics: determinants of survival and growth in the gut .sup. 1-3", Am. J. Clin. Nutr. 2001 73 (Suppl): 399S-405S) ..

Closest to the claimed is the pharmaceutical composition of hydrolytic lignin, oligosaccharide (mainly fructooligosaccharide) and lactulose disaccharide, used as a treatment for certain diseases of certain sections of the gastrointestinal tract, including bacterial viral and protozoal infections, food poisoning, acute and chronic hepatitis and cirrhosis, diarrhea, peptic ulcer disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, malabsorption of calcium and magnesium ions, including osteoporosis and other bone formation disorders, as an immunomodulating agent in the treatment of atopic dermatitis and other immunodeficiencies, for the protection and restoration of intestinal microflora after antibiotic therapy, chemotherapy and radiotherapy (WO20071 17175, 2007, prototype - ((PHARMACEUTICAL COMPOSITION OF ENTEROSORBENT AND PREBIOTICS, DOSAGE AND THE METHOD FOR PREVENTION AND TREATMENT OF GASTROINTESTINAL DISORDERS)), A61K36 / 00; A61J3 / 00; A61K31 / 7016; A61K31 / 702; A61P1 / 00; A61K36 / 00; A61J3 / 00; A61K31 / 7016; A61K31 / 702; A61P1 / 00A61K31 / 7016.

However, the above combination of prebiotics and dietary fiber-enterosorbents has significant drawbacks that do not allow the necessary completeness of the removal of toxic substances and normalization of the intestine to prevent their more effective use for general detoxification of the body, faster elimination of pathological manifestations in the digestive tract, and normalization of microbiocenosis in its various departments and normalization of the general condition of the body.

It is known that natural insoluble dietary fibers, such as natural lignin, cellulose, have a relatively low ability to bind and remove fat-soluble poisons from the body, such as organic solvents, chlorine-containing organic pesticides, certain drugs, for example, such as anesthetics, hypnotics, sedatives, etc., exogenous poisons that enter the body through the mouth, and endogenous toxic substances, such as bile acids deconjugated by pathogenic bacteria, excessive amounts of cholesterol, endotoxins of bacteria). In all these cases, with pronounced (acute) intoxications, a differentiated approach is provided when choosing means for detoxifying the body, which differ, depending on the nature of the toxic substances that caused the poisoning. In particular, in addition to the above insoluble dietary fiber, well-known enterosorbents such as activated carbons (DO Cooney, Activated Charcoal Antidotal and other Medical Uses. Marcel Dekker, New York and Basel, 1983) are not sufficiently effective for poisoning by many fat-soluble substances.

G. Park, et al., "Expanded role of charcoal in the poisoned and overdosed patient." Arch. Int. Med. 146: 969-73, 1986). Therefore, when emergency conditions arise, for the binding of fat-soluble toxic substances, for example, vegetable oils or non-edible fats, such as paraffin oil, are used.

Due to the relatively low ability to bind fat-soluble substances, the considered compositions are practically not able to significantly affect lipid metabolism, cholesterol metabolism, which are disturbed during various diseases and intoxications, leading, in turn, to the development of concomitant pathologies (increase in the level of “bad” cholesterol in the blood, deposits of excess cholesterol in the vessels (atherosclerosis) and in the gallbladder (cholesterol stones in gallstone disease) .In some cases (for example, when using activated carbon) a critical factor is not only the low overall ability to bind high polymer fats, but the inability to use the sorbent for a long time due to the strong elimination of useful nutrients (vitamins, microelements) bound in food. In other cases, for example, with respect to mineral adsorbents obviously their sorption ability with respect to hydrophobic substances is insufficient.

The disadvantage of all the analogues described above - the compositions of sorbents and prebiotics is the fact that they are made in the form of pharmaceutical or consumer forms for quick oral administration (tablets, suspensions, powders), so that the presence of such compositions in the oral cavity is very short-lived and when the presence of toxic substances here (for example, due to the development of any dental disease in the oral cavity (caries, inflammation), effective binding of such toxin in the oral cavity does not have time to descend.

Finally, all the described compositions based on insoluble dietary fiber have unsatisfactory taste properties (especially mixtures with hydrolytic lignin), are retained on the mucous membrane of the oral cavity, causing a long unpleasant aftertaste, require drinking plenty of water. All this makes such compositions uncomfortable and often unacceptable for their use in young children.

Thus, the known composition, including insoluble dietary fiber and oligosaccharide prebiotics, are characterized by a number of disadvantages, namely:

- insufficiency of the wide spectrum of sorption activity of insoluble dietary fiber used as an enterosorbent in relation to fat-soluble (hydrophobic) toxic substances;

- insufficiently high binding and inhibitory activity of the individual components of the combined preparation against pathogenic microflora, mainly developing with dysbiosis;

- the absence of a significant effect on the ratio of "good" and "bad" cholesterol in the blood in the presence of lipid composition disorders and a tendency to develop vascular atherosclerosis;

- unsatisfactory consumer properties of finished products or dosage forms created on their basis, including unsatisfactory organoleptic characteristics that narrow the volume of consumption and commercial attractiveness of products.

Disclosure of the invention

An object of the invention is the creation of an effective and edible composition that provides for the full recovery of the body due to the rapid removal of toxins from all parts of the digestive tract, including the entire gastrointestinal tract (GIT), increasing the overall resistance of the body while normalizing the composition of its microflora including prevention of enteric dysbiosis, for example, during antibiotic therapy, as well as expanding the arsenal of compositions suitable for cleansing org anism against toxins and normalization of microflora.

The technical result that provides the solution of the problem lies in the fact that the range of functionality has been expanded, due to the increased efficiency of using the sorption properties of enterosorbent, in particular due to the fact that the developed product is suitable for detoxification, namely for enhanced binding and simultaneous excretion from the body a wide range of toxins of various origins, and due to this - for faster healing of the body while normalizing the state of microflora to ischemic, disturbed due to a variety of non-infectious and infectious diseases of the gastrointestinal tract. At the same time, pathogenic microbes are removed and the state of the gastrointestinal tract is normalized, the effect of irritation of the mucosa of the upper digestive tract (oral cavity, esophagus, stomach) by sorbent particles is reduced and the severity of inflammatory processes in the mucous membranes of the gastrointestinal tract is reduced. A composition of this composition also promotes indirect (in the composition of fatty micelles) binding to a sorbent of water-insoluble (hydrophobic) toxic substances; correction of digestive disorders associated with dysbiosis and optimization of the ratio of "bad" and "good" cholesterol in human blood. Due to the use of solid fat at room temperature in the composition optimal shaping is achieved, providing a consistency convenient for storage and use, uniform distribution of sorbent particles over the product volume and ease of release of the crushed sorbent in the body due to the rapid melting of the fusible fat component directly in the gastrointestinal tract at the temperature of the human body. The advantages of the product include ease of use - easy chewing, in contrast to the previously described hard tablets of the closest analogue or activated carbon tablets, which for children or people who have difficulty swallowing due to inflammatory diseases in the mouth, pharynx, and esophagus are recommended to be crushed beforehand; or from an analogue made in the form of a powder that has high adhesion (sticks to the tongue) and requires rinsing the mouth after taking the drug (typical for almost all enterosorbents in the state of the powder, and is especially pronounced for mineral sorbents (such as smecta) or hydrolysis lignins. Through the use of a binder of edible fat, an excellent masking of the unpleasant taste of the sorbent is achieved (for example, a taste resembling the taste of sawdust with lignin or the acidic taste of activated carbon, a mineral aftertaste of alumina); Enhanced organoleptic characteristics allow expanding the volume of consumption and commercial attractiveness of the product.

The use of widely used edible fat in the composition can significantly expand the industrial applicability of the product through the use of universal high-performance equipment of the food industry.

The essence of the utility model is that the composition for normalizing microflora and cleansing the body of toxins contains at least one insoluble enterosorbent, cocoa butter and a prebiotic, and the enterosorbent and prebiotic are contained in the composition in the form of a powder with a particle size of not more than 65 microns, with the following content of components, in mass%:

- enterosorbent 1-50%;

- cocoa butter 5-60%; - prebiotic 1-50 mass%.

Preferably, the insoluble enterosorbent is an insoluble dietary fiber from the group: lignin, vegetable fiber, bran, cellulose and its esters, microcrystalline cellulose, highly esterified insoluble pectin, or a mineral from the group: zeolite, attapulgite, smectite, silicon dioxide, silica .

Cocoa butter in the developed utility model simultaneously performs the function of a binder - filler, the function of shaping in the manufacture and temperatures below 33-37 ° C, as well as the function of the sorbent of fat-soluble substances when it enters the gastrointestinal tract.

The composition contains a prebiotic in the form of an oligosaccharide from the group: lactulose, lactitol, fructooligosaccharides, galactooligosaccharides, xyloooligosaccharides, maltooligosaccharides, inulin, arabinogalactan, isomalt, and contains enterosorbent with a moisture content of not more than 5 wt%.

The composition further comprises at least one flavoring agent, preferably a food flavoring or flavoring agent, and / or at least one natural or identical to a natural food coloring in an amount of not more than 3% by weight.

The composition may be solid in homogeneous consistency.

The composition may contain lecithin in an amount of not more than 1 mass% as an emulsifier.

The composition may be made by casting the melt into molds.

The composition can be made in the form of a lozenge (tile, bar) of any technically feasible form when casting, for example, oval, round, rectangular, square or in the form of nuts, coffee beans, figures of animals or fish, etc.

The composition can be made homogeneous in a paste form.

The composition may, in specific variants of its execution, contain as a means of increasing the sorption efficiency of toxic substances, and also, as a diluent and plasticizer, an auxiliary substance is liquid paraffin in an amount of up to 20 mass%.

Used in the inventive composition, cocoa butter with a melting point not higher than 39 ° C, refers to solid edible fats. Cocoa butter, practically do not contain trans isomers of fatty acids, which are considered by some experts as ballast and harmful to the body, and which in some countries are not approved for use in baby food. As a natural product, cocoa butter has no age restrictions on its use in nutrition. Therefore, the compositions of the claimed composition can be included in diets in the form of biologically active additives or functional food products for people aged 3-5 years and older.

Through the use of the product in a consumer form suitable for chewing (pastilles, tiles) or in pasty form, the possibilities of using both the enterosorption and prebiotic properties of the composition are expanded. So, unlike the forms in the form of tablets or aqueous suspensions, when chewing, the residence time of the composition of sorbents and prebiotics in the oral cavity increases, while the composition already melts in the oral cavity, which makes it possible to more effectively bind harmful substances contained in the oral cavity (for example, exogenous residues toxic substances or toxic products that accumulate during caries or other diseases of the oral cavity). The prebiotic components of the composition, which are partially released when chewing the composition into saliva and are retained in the composition of the fat “film” on the oral mucosa, can have a positive effect on the oral microbiocenosis in various dental diseases. Entering the subsequent sections of the gastrointestinal tract, the fatty base of the composition goes into a highly plastic (fluid) state in the stomach, where during active mixing it is able to bind many fat-soluble substances, interfering with their absorption, unlike aqueous suspensions of many sorbents that are able to bind predominantly hydrophilic , slightly soluble in fats. Already in the acidic environment of the stomach begins 10 000802

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hydrolytic destruction of the fat base of the composition occurs, and after the mixture arrives from the stomach in the upper sections of the small intestine due to the effective action of intestinal lipolytic enzymes on the fat base of the composition, the enterosorbent microparticles are quickly released with the formation of highly dispersed suspensions / emulsions (in comparison, for example, with traditional tablet forms, the breakdown of which often does not have time to complete not only in the stomach, but also in the upper parts of the small intestine, and only gradually increases I have them available for the adsorption surface). The surface of the enterosorbent particles is largely released from under the lipid film, but at the same time partially continues to retain the particles of lipid microemulsions with hydrophobic substances dissolved in them. Thus, in the upper intestine, the universal properties of the composition, which acquires the ability to effectively bind both hydrophilic and fat-soluble substances, are fully manifested.

The used form of the composition has a positive effect on the organoleptic properties of the product, it eliminates or significantly reduces the unpleasant taste sensations from the effects of many sorbents (the taste of wood sawdust of lignin hydrolysis, an unpleasant sour taste of activated carbon, some mineral sorbents based on alumina, etc.) as well significantly reduce the irritating effect of sorbent particles on the mechanical (tactile) receptors of the tongue and oral mucosa, giving a suspension To the sensations and disintegrating tablets in the mouth there are unpleasant sensations of gross “granularity”. The adhesion (adhesion) of the sorbent particles to the surface of the mucosa is significantly reduced, and therefore taking the drug does not require washing it down with a large amount of water. The latter is especially important if it is necessary to take the drug outdoors.

The technological advantages of the proposed composition options are that the proposed approach can significantly expand the possibilities of manufacturing affordable and convenient forms of the product for mass use, both its medicinal options and non-drug consumer forms (dietary supplements, functional food products, etc.) · Products of the specified composition and properties can be made, in particular in the form of lozenges or chewing bars or pastry-type pastes, which makes it possible to use high-performance food production equipment for their manufacture. Thus, a significant expansion of the field of technological implementation of the composition is achieved.

The composition, as a biologically active additive, of the claimed composition and method of preparation can be recommended for regular use by the population living, for example, in ecologically disadvantaged regions engaged in hazardous industries or suffering from chronic diseases accompanied by endogenous intoxication (infectious and non-infectious diseases of the liver, kidneys, intestines), as well as a product for the prevention of cardiovascular diseases, atherosclerosis.

The composition can be made on the basis of a known sorbent - for example, a mineral enterosorbent such as smectite, zeolite, alumina, silica gel, hydrolysis lignin, microcrystalline cellulose. A composition based on the listed ingredients is made in the form of a paste, lozenge, tile or chewing bar. An emulsifier (for example, lecithin in an amount of not more than 2% by weight), as well as taste correctors (flavoring, sweetener, cocoa powder, etc.) in quantities necessary to impart a proper taste sensation can be introduced into the product.

In addition, to obtain the product of the required consistency, the composition may include permitted for use in food products and (or) pharmaceutically acceptable excipients (cellulose derivatives, antioxidants, preservatives.

An important property and feature of the proposed composition is the use of sorbent powders having a particle size of not more than 65 microns in its composition. Particle size affects the basic properties of the composition in a direct way. Firstly, it is widely known that the sorption ability of sorbents strongly depends on the particle size: the larger the total surface area, the higher the total sorption capacity of the sorbent. Total area particle surfaces the higher, the smaller their geometric mean diameter. At the same time, excessive grinding of the sorbent leads to the manifestation of negative aspects: 1) product losses increase sharply, since the efficiency of obtaining very small (less than 10 microns) particles by known methods and devices quickly decreases; 2) if the particle sizes are too small, the internal porous structure of many sorbents is destroyed, which does not lead to the further expected increase in their sorption capacity, but, on the contrary, to its rapid decline. 3) the manufacturability of the product decreases, which acquires the ability to quickly transition to a suspended state (“volatility” of powders) with an increase in technological losses at the production stages; 4) at the same time, the sanitary and hygienic conditions of production are deteriorating (the dustiness of the premises is growing):

At the same time, the particle size of the products entering the body through the mouth is also important from the point of view of taste sensations if these products are in the oral cavity for a long time. It is known that the mechanoreceptors of the tongue are able to sense small particles "separately" with their size above about 60-65 microns. Organoleptically, this is described as a pronounced "granularity" of the product, and with severe irritation of the receptors it causes unpleasant reactions, up to emetics. With smaller particle sizes, the product is perceived as a homogeneous "paste" that does not cause irritating "perspiration".

Together, all of the above effects provide the claimed composition with an increased ability to prevent the effects of chronic poisoning with harmful substances, poisons that enter the body from the outside, or accumulate in the body with various diseases; supplemented and enhanced the healing effect of each of the individual components:

a) the sorption properties of the known enterosorbent in relation to various toxic molecules are expanded by introducing into the composition a fat component in the form of cocoa butter with a melting point below the temperature of the organs of the gastrointestinal tract, absorbing fat-soluble toxic substances in the molten state, but at the same time while retaining the ability to bind amphiphilic and water-soluble toxins with emulsions containing enterosorbent, as well as particles of enterosorbents released from the composition as the fat is partially broken down by gastric lipase and pancreatic lipase in the small intestine;

b) fatty acids - products of hydrolysis of cocoa butter or its substitutes or surrogates with intestinal lipase - also contribute to faster restoration of membranes of damaged liver cells and other organs of the body, which is especially important when using the developed product to repair damaged tissues during intoxication;

c) in a preferred embodiment of the direct use of cocoa butter in the composition, in addition to the function of binding fat-soluble poisons, the products of lipolytic cleavage of the oil (medium chain fatty acids) contribute to the effective emulsification of the components of the food lump in the intestines even with a deficiency of their own emulsifiers, such as bile acids (for example, with violations of the formation or outflow of bile from the gallbladder) with various diseases;

d) cocoa butter has an independent anti-inflammatory effect, protecting, together with prebiotic oligosaccharides, the mucous membranes of various parts of the gastrointestinal tract from traumatic chemical and mechanical influences;

e) acting in conjunction with an enterosorbent that binds toxic substances, the prebiotic in the composition of the composition stimulates the development of beneficial intestinal microorganisms and in the same way significantly accelerates the elimination of such adverse effects of intoxication as dysbiosis (dysbiosis), especially pronounced in case of intestinal infections, as well as severe poisoning, causing damage to the mucous membrane of the organs of the gastrointestinal tract, malnutrition, etc. f) stimulating the normalization of intestinal microflora, promoting the active reproduction of beneficial microorganisms (especially bifidobacteria, lactobacilli), the prebiotic in the composition also has a positive effect on the normalization of the immune system, especially local, organ-tissue level, which provides an increase in the body's resistance to diseases of the gastrointestinal tract of both infectious and non-infectious nature;

g) with an increase in the efficiency of binding and elimination of fat-soluble substances, including such as cholesterol and (or) excessive amounts of bile acids, the effectiveness of the composition in normalizing fat metabolism and improving the ratio of “good” and “bad” cholesterol in the blood also increases , reducing the risk or slowing the development of atherosclerosis of blood vessels;

h) the prebiotic included in the composition not only provides an effective normalizing effect on the composition of the intestinal microflora, but also increases the efficiency of calcium absorption in the colon, reducing the risk of osteoporosis.

Figure 1 shows the beginning of the breakdown of the fat composition with the lignin enterosorbent particles included in it, Fig. 2 shows a sample after 30 minutes of incubation of the sample in a medium simulating the composition of the digestive secretion of the small intestine, Fig. 3 shows a micrograph of the emulsion after 15 more minutes of mixing with an increase in X200, figure 4 - sample after 45 minutes of incubation of the sample in a medium that simulates the composition of the digestive secretion of the small intestine with an increase of x400.

Options for implementation

EXAMPLE 1. Preparation of a composition in the form of a biologically active additive

Dietary supplement "Filtrum Safari" to normalize microflora and cleanse the body of toxins in the form of lozenges is made as follows.

1. For the production of the drug, the following raw materials are used:

- enterosorbent - hydrolysis lignin (for example, "polyfan", according to FSP 42-0236-06; powder containing hydrolysis lignin for oral administration); 00802

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- prebiotic - powder of dry fructooligosaccharides - registered raw materials for the production of biologically active additives

- cocoa butter (in an embodiment, a cocoa butter substitute may be used (for example, Ekolad confectionery fat according to TU 9142-

016-57710951-2005);

food lecithin

- natural or any other flavoring approved by regulatory authorities for use, as part of B AD or drugs.

An example of calculating the consumption of raw materials per 10 kg of finished products (Table 1).

Table 1

2. Product manufacture.

2.1 Wet granulation

Getting wet granules is carried out on a universal granulator. Set the mesh with a hole diameter of 4 mm. The wet mass of hydrolytic lignin - “polyphane” is scooped into the granulator hopper. Wet granules are collected in a container, closed with a lid, a filled-in label of an established sample is glued and transferred to the “Drying” stage.

2.2 Drying of lignin granules.

Drying is carried out in an apparatus for drying multicomponent mixtures. Wet granules of hydrolytic lignin - "polyphane" are loaded into the dryer food tank. The trolley with the tank is rolled into the dryer and fixed. Set the drying mode - incoming air temperature + 60-70 ° C, compressed air pressure of 0.4 MPa (4 kgf / cm).

Turn on the dryer. During drying, purified heated air is supplied to the working area of the apparatus. Air enters the food tank from below and, passing through the thickness of the wet mass, brings it into a balanced state, mass is fluidized. During the drying process, you must periodically manually mix the mixture in the tank, shake the bag filters in order to clean them from dust. The drying process is continued at an inlet air temperature of + 60-70 ° C, to a residual moisture in the granulate of not more than 4.5%. The dry mass is unloaded in a container, closed with a lid, a filled-in label of an established sample is glued and transferred to the “Grinding” stage.

2.3 Shredding

The grinding of dry granules is carried out in a rotary mill. Set the mesh with a hole diameter of 2.0 mm. Grinding is carried out with exhaust ventilation switched on, using personal protective equipment. Caution, avoiding dust formation, the granulate is loaded into the hopper of a rotary mill, grind and collect the resulting powder in a container. The containers are closed with a lid, pasted on the filled labels of an established sample and transferred to the stage of "Screening".

2.4 Screening

The fructooligosaccharide powder is sieved through a nylon sieve No. 23, and the lignin powder through a nylon sieve No. 76.

Sifting is carried out with exhaust ventilation turned on using personal protective equipment, after checking the cleanliness of the mesh and capacity for receiving sifted raw materials. Sifting of each type of raw material is carried out separately.

Containers with sifted raw materials and lignin powder are covered with a lid, the filled labels of an established sample are pasted and transferred to the “Dosing and Mixing” stage.

2.4. Dosing and mixing

The components of the formulation are pre-weighed on a scale, in quantities determined by the norms of consumption of raw materials, then fed into a heated thermostatic mixer. Cocoa butter (or its substitute) in the mixer is preheated at a temperature not exceeding 45 ° C, with constant stirring until completely melted, then lecithin, lignin powder are added and mixed until a uniform mixture is obtained. TO the pre-weighed and sieved powder of fructooligosaccharides is added to the resulting mixture. Mixing is carried out until a homogeneous mass is obtained. The flavor is introduced into the mass at the end of mixing the prescription components.

2.5. Molding

The resulting mass is poured into casting molds, preheated to a temperature of + 40 ° C. For uniform distribution of mass in the cells of the mold and removal of excess mass from the surface of the mold, the latter is cleaned with a scraper. Cells of casting molds can have any desired configuration (custom-made), which in size provides a given average mass of products.

Excess mass is collected in a container for excess mass and returned to the stage of preparation of the molten mass 2.4.

After that, the filled forms are placed on a vibrating table, for uniform distribution of mass throughout the entire volume of the cells of the forms.

2.6. Cooling

Forms with products are cooled in a medium-temperature refrigerating cabinet (type ШХ-27) at a temperature of + (5-7) ° С for 40-45 min. In order to avoid the effects of "greasy blooming" on the surface of finished products based on cocoa butter, they are gradually cooled in steps according to a predetermined program (a special tempering machine can be used to produce chocolate products)

2.7 Extract from forms

Removing the pastilles from the molds is carried out on the packing table. To remove products from the molds, the latter are struck on a hard smooth surface with the front side;

When removing pastilles from the forms, the average weight of the pastilles is controlled by weighing 20 pastilles on the scales. The average mass of lozenges should be 2.75 g ± 10%, the mass fraction of moisture is not more than 2.5%.

Conditioned lozenges are collected in a container for conditioned lozenges, weighed on a scale, a filled-in label of an established sample is pasted and transferred to the “packing and packaging” stage. Non-standard pastilles, without mechanical impurities, rejected by weight and appearance, are collected in a container for non-standard pastilles, weighed, pasted on a filled label of an established sample and transferred to the stage of “Collecting excess mass for processing”.

3. Packing and packaging

Packing and packaging of the drug in consumer packaging is carried out in:

- blister packs (blisters) of aluminum foil and polyvinyl chloride film;

- polymer cans;

- polystyrene containers.

- contour film "Correx".

- into plastic tubes for tablets.

- bags made of polymer food film.

Other suitable forms of product packaging may be used. Primary packaging with products (lozenges) can be placed in secondary packaging (for example, a cardboard box, or a cardboard or plastic container).

The number of lozenges in consumer packaging is 3, 6, 9, 10, 12, 18, 21, 24, 30, 40, 60, 90, or 100 pieces.

4. Characterization of consumer properties of the drug:

The drug is a lozenge with the trade name Filtrum Safari intended for sale to the population as a complex source, insoluble dietary fiber (enterosorbent lignin) and prebiotic (fructooligosaccharides) to normalize the intestinal microflora and cleanse the body of toxins. According to the organoleptic characteristics, the lozenge for the normalization of microflora and cleansing the body of toxins "Filtrum-Safari" of the claimed composition corresponds to the indicators shown in Table 2. Table 2

According to physico-chemical parameters, the lozenge corresponds to the indicators indicated in Table 3.

Table 3

EXAMPLE 2. The manufacture of the composition in the form of a functional food product - confectionery paste

The technological process of preparing a functional product consists of the following operations:

1. Preparation of raw materials for production

Insoluble enterosorbent - dietary fiber - lignin, as well as prebiotic - lactulose, are pre-crushed to form powders with a particle size of not more than 65 microns. The powders are sieved and passed through magnets to remove any metal microparticles (including those that appear in the product during grinding). The moisture content of the powders should not exceed 5%.

2. Preparation of a mixture of bulk components

The powder of insoluble lignin and lactulose is mixed in the ratios indicated in the formulation until a uniform distribution components among themselves at room temperature and normal humidity in the room.

2. Preparation of the fat base.

Before use in production, a fat mixture is prepared: cocoa butter is melted at a temperature of 60 ° C, mixed with an equal amount of melted butter (with a fat content of 82%), and with continuous stirring, sunflower oil heated to the same temperature is added to the constantly heated fat mixture (or corn) or liquid paraffin, (in an amount of 40-50% by weight of cocoa butter); the resulting fat mass, while maintaining the temperature in the mixer 42-45 ° C, is thoroughly mixed until a plastic flowing (creamy) consistency is reached. If necessary, the consistency of the product is adjusted to the desired one by adding solid fusible or, conversely, liquid fat.

3. Cooking pasta.

To the mixture of lignin and prebiotic powders add a fat mixture (heated to a temperature of 42-45 ° C), mix thoroughly until a homogeneous pasty mass is obtained, add the necessary amount of flavoring agents (for example, cocoa powder in an amount of up to 2-3% by weight or natural flavoring in an amount of up to 0.5-1% by weight and again thoroughly mixed while gradually cooling the mass to room temperature All components (ingredients) of the composition are taken in quantities, based on the preparation of the composition at the following content components in mass%: Insoluble enterosorbent (lignin hydrolysis) 20 -30%;

prebiotic (lactulose) 10-20%;

fat base 50-60%.

flavors and flavoring agents up to 2-4%

Parameters to be controlled: mass of loaded components; consistency of the mass.

Controlled process (stage): loading components into the mixer; cooking pasta. Control methods: the mass of the loaded components is weighted, the consistency is organoleptically, the consistency should be homogeneous, creamy.

Frequency of control: each download.

4. Packing and storage

The resulting paste is Packed in sealed glass, tin or plastic containers.

The product must be stored in dry, clean, well-ventilated warehouses, which do not have foreign smells, at a temperature of 18 ± 2 ° С and relative humidity of air no more than 75% before packaging in sealed containers.

The shelf life of the product on a fat basis, subject to storage rules, is up to 18 months from the date of manufacture.

Parameters to be controlled: temperature and relative humidity.

Controlled process (stage): cooling the mass of finished lime.

Control Methods: Temperature and Humidity Meter

Frequency of control: each batch.

An example of the formulation of the composition in the form of a functional fat-based product (based on lignin and lactulose) is shown in table 6.

Table 6.

Name Mass fraction $ Consumption of raw materials, kg

dry raw materials per 5 kg of products per 1 ton of finished products of substances,%

in kind in dry in kind in solids substances

Lactulose 99.00 1.28 1.26 256.00 253.44

Lignin 95.00 0.66 0.62 132.00 125.40 hydrolysis

Fat base 99.00 3.14 3.10 628.00 621, 72 (cocoa butter: butter

butter

sunflower)

Flavoring - 0.03 - 6.00 -

Total - 5.07 4.98 1023 1000.56

Yield 98.00 5.00 4.90 1000.00 980.00 EXAMPLE 3

Evaluation of the effectiveness of the release of lignin enterosorbent from the composition in a medium that mimics the contents of the small intestine of a person.

Study progress:

The lozenge of the Filtrum-Safari dietary supplement (according to Example 1) was crushed and placed in a beaker, which was then placed in a water bath preheated to 38 ± C. 100 ml of 0.05 M phosphate buffer solution (pH = 7.0) in the measuring cylinder was set to warm up in the same water bath. When the lozenges melted, about 30 ml of the heated buffer solution was added to it, the homogenizer was lowered into the glass and they were mixed until uniform.

We took a sample of pancreatin with a lipase activity of 37 IU / mg - 200 mg (with the calculation of obtaining 5000-6000 IU of lipase in solution). Pancreatin was dissolved in the remaining volume of the buffer solution and added to a glass with lozenges. Then 5 ml of bile was added there. The homogenizer was turned on again and the sample was thoroughly mixed, achieving the formation of a thin emulsion.

In the process of mixing, the temperature of the mixture was controlled, not exceeding 40 ° C, in order to avoid inactivation of enzymes.

In order to compile a complete picture of the course of the experiment,

"Control points." T.O. every 15 minutes, certain parameters were recorded to monitor changes occurring over time.

To determine the degree of lipolytic cleavage of the fatty base, the lozenges monitored the clarification of the emulsion.

Turbidity changes of the sample were monitored visually. Also, at each stage, the emulsion was microscopied to provide a complete picture of the hydrolysis of the fat base.

Results and their processing:

As a result of visual inspection of the color of the sample, it was revealed that the emulsion

(consisting of lozenges, pancreatin and bile in a phosphate buffered saline) during the first 15 minutes of incubation noticeably brightened. AT the next 30 minutes, the mixture also became lighter, but not so significant.

Microscopy of the emulsion at each stage of the experiment, as well as visual observation, showed significant changes, which were especially clearly recorded after 15, 30 and 60 minutes of mixing.

Changes were noted both in the structure of the lozenge itself and in its individual components (in particular the fat base).

The processing results are illustrated by drawings (see. Appendix).

The result of microscopy of the emulsion after 15 minutes of incubation in a water bath with constant stirring is presented in the picture:

Figure 1 shows the beginning of the breakdown of the fat composition with particles of the lignin enterosorbent incorporated therein. The result of microscopy of the emulsion after 15 minutes of incubation in a water bath with constant stirring

In the first control point, the separation of the fat base into fat droplets was observed (Fig. 1), which indicated the beginning of the process of hydrolysis of the fat of the lozenge of pancreatin lipase.

Figure 2 shows the sample after 30 minutes of incubation of the sample in a medium that simulates the composition of the digestive secretion of the small intestine. Despite thorough mixing by a homogenizer, lignin, as an amphiphilic component, still partially remained included in the fat emulsion (Fig. 2), which proved the insufficiency of 30 minutes of incubation.

Figure 3 shows a snapshot of the emulsion micropreparation after another 15 minutes of stirring with an increase in X200.

Figure 4 shows the sample after 45 minutes of incubation of the sample in a medium that simulates the composition of the digestive secretion of the small intestine with an increase of x400.

The micrographs clearly show that in the process of emulsification and exposure to pancreatic enzymes, the particles of enterosorbent lignin are released from the complex with fats (Figs. 2, 3). There are more fat droplets, their average size has decreased. Findings:

1. Within 30 - 45 minutes in an artificial environment that simulates the composition of the digestive secretion of the small intestine, the composition of insoluble enterosorbent, soluble prebiotic and fat breaks down into its constituent parts. At the same time, if the molten fat in the stomach includes sorbent particles, and is capable of simultaneously absorbing fat-soluble substances by partially incorporating large fat droplets into the volume, then as environmental factors in the small intestine are exposed, the fat component passes into the microemulsion state (having a significantly larger interaction surface with fat-soluble and amphiphilic substances), and enterosorbent particles are released from the composition and acquire the ability to sorb substances in accordance with its sorption properties.

EXAMPLE JV "4. Evaluation of the sorption activity of the claimed composition

To evaluate the sorption activity of the claimed product, the in vitro sorption efficiency of fat-soluble substances (beta-carotene and Sudan III dye), as well as water-soluble substances (methylene blue dye, gelatin protein) and Escherichia coli bacteria were evaluated in comparison with the initial enterosorbent - hydrolytic lignin. For this, the lozenges of the composition according to example 1 were melted at a temperature of 39 ° C in a water bath, then the melt was added to 100 ml of artificial gastric juice (0.1 m HCl with the addition of pepsin), emulsified thoroughly and mixed for 1 hour with an immersion mixer with the solutions of the studied sorbents: 3 ml of a solution of beta-carotene in chloroform (500 μg / ml), or 3 ml of a solution of Sudan III in chloroform (1 mg / ml); or 5 ml of an aqueous solution of methylene blue (40 mg / ml) or 5 ml of an aqueous solution of gelatin (5 mg / ml), or 3 ml of a suspension of bacteria of Escherichia coli containing bacteria (1-2) 10 ⁸ / ml (sample N ° l ) A sample with a control on the effect of lipolytic cleavage (sample Ν ° 2) was prepared in the same way, but after thorough mixing with artificial gastric juice, 10 ml of a 10-fold phosphate buffer solution with pH 8.5 and 0.5 g of pancreatin powder were added to the sample ( ~ 3000 PIECES of lipase), 0.3 g of dry bile. The sample was incubated for 1 hour at 38 ° C in a water bath with continuous vigorous stirring. After that, the solutions of the tested sorbives in the quantities indicated for the sample N ° l were added to the sample. Control samples N ° N ° 3 and 4 contained hydrolysis lignin and fructooligosaccharides in an amount equivalent to their content in lozenges (samples N ° N ° 1 and 2), but without the addition of fat. Control samples N ° N ° 5 and 6 instead of hydrolyzed lignin contained known entrosorbents activated carbon and enterosgel, the amount of sorbent in which on a dry matter was the same as the amount of lignin in lozenges. Sample processing was carried out similarly to the processing of samples N ° l and N ° 2, respectively.

In the process of sample processing, aliquots were periodically taken and analyzed microscopically (light microscope, X20 lens).

At the end of the incubation with the UH sorbents, the volume of each sample was centrifuged (6000 g, 15 min), and water and fat were separately quantitatively collected. Phase In the aqueous phase, the content of sorbing dyes was determined spectrophotometrically, and the protein was determined by the microbiuret method. In order to determine the sorption of bacteria, the second half of each sample was filtered through a paper filter pre-moistened with buffer, and the bacteria content in the filtrate was determined by direct counting in a Goryaev counting microchamber. The correction for the possible binding of bacteria to the filter was calculated by filtering the suspension of bacteria through the same filter.

To determine the content of fat-soluble dyes in the collected fat phase after centrifugation, the latter was dissolved in hexane and the dye concentration was determined spectrophotometrically.

The degree of sorption (sorption capacity) was determined by the difference in the amounts of sorbents in the aqueous phase before and after mixing with the sorbent, and for the fat-soluble dyes, the fraction of the substance transferred to the fat phase was also taken into account.

The experimental results are shown in table 7. Table 7.

From the results of the experiment it follows that the combined preparation based on the sorbent of lignin and fat is able to efficiently bind both fat-soluble and water-soluble substances with different molecular weights, while lignin in a mixture with fructooligosaccharides effectively binds predominantly water-soluble substances and bacteria. Taken in equal amounts, other types of enterosorbents showed significantly lower sorption rates for almost all types of substances studied, with the exception of the relatively low molecular weight polar dye methylene blue.

JVs Example 5

Detoxification and normalization of microflora as an example of protection against the death of mice in experiments with enteropathogenic E. coli strain Objective: to conduct in vivo tests of therapeutic and prophylactic drugs based on the prebiotic of lactulose and insoluble dietary fiber - hydrolytic lignin with the addition of cocoa butter to determine the therapeutic and prophylactic efficacy of drugs in modeling infection with the toxigenic strain E. coli 0157 in mice with experimental dysbiosis.

The tests were subjected to preparations of the compositions:

Lozenges containing Fructooligosaccharides - 40 wt.%

Smectite dioctahedral - 10 wt.%

Cocoa Butter - 50 wt.%

The paste containing Lactulose - 10 wt.%

Hydrolytic lignin - 30 wt.%

Fat base with cocoa butter -60 wt.%

As comparison drugs in the experiment used drugs of the compositions;

Fructooligosaccharides - 55%

Smectite dioctahedral - 45%

Lactulose - 25 wt.%

Hydrolytic lignin - 75%

Crystalline lactulose (-95% lactulose content)

Smectite dioctahedral (basic substance content 90%)

Hydrolytic lignin (content of the main substance 92%)

Saline

Experimental technique

1.2.1. Modeling of dysbiosis in animals (hybrid mice (line

"Black" F1) of both sexes, weighing 10-12 g.

Dysbacteriosis in mice was induced by oral administration of a doxycycline antibiotic through a rigid probe, according to the method proposed by V. Likhoded (“The state of anti-endotoxin immunity in experimental intestinal dysbiosis in mice,” Likhoed et al., 1998). The introduction of doxycycline. The administration of doxycycline to animals was carried out daily at a dose of 0.2 mg. The duration of the course was 3 and 10 days. To obtain the desired concentration, 1 capsule (100 mg) was dissolved in 250 ml of a sterile isotonic sodium chloride solution, obtaining a drug concentration of 0.4 mg / ml, followed by a 0.5 ml dose to mice. The control group consisted of intact animals and mice that received per os 0.5 ml PBS.

1.2.2. Study of the composition of the intestinal microflora of mice after the introduction of antibiotics.

To assess the quantitative composition of microflora, the technique proposed by I. A. Bochkov et al. (1988) was used. Three groups of animals were formed by random sampling:

Group 1: mice after oral administration of Ampiox (5 days, 0.4 mg / 0.5 ml PBS) (n = 10);

Group 2: mice after oral administration of PBS (5 days; 0.5 ml each)

(n = 10);

Group 3: intact mice (n = 10).

Each of these groups of animals, 24 hours after the last administration of the antibiotic, took an exact weighed sample of feces (2 g).

The obtained samples were dissolved in PBS to a concentration of 0.1 g / ml. Then, serial ten-fold dilutions of each sample were performed (3 repetitions). Material from the resulting dilutions of the initial suspension from 10 ^"3 to 10 ^{~ 7 is} seeded onto the surface of a number of dried elective culture media (Saburo medium, Endo agar, vitelline salt agar, lacto- and bifidoagar) in the form of three isolated drops. It is possible to place up to one cup 15 isolated drops, the volume of one drop was 15 μΐ.

Crops on Endo medium were cultured at 37 ° C for 24 hours; on salt agar - at 37 ° C for 72 hours; on Saburo medium - at 22-24 ° С for 8 days. Cultures, seeded on laktoagar, were within 3 days of CO in the incubator containing 5% C0 ₂ at 37 ° C. Cultures to bifidoagare Anaerobic cultured at 37 ° C for a day. Count the number of colonies grown in different dilutions. The number of microorganisms in 1 g of feces was determined by the formula:

X = (2.2 10 ⁿ [ai + a ₂ + a ₃ ]) _{/ P} ,

where 2.2 is the conversion factor; p is the degree of dilution of the initial suspension; a _1} a ₂ , and ₃ - the number of colonies in a drop; p is the concentration of feces in the initial solution.

The identification of microorganisms cultured on the Endo medium was carried out using the “Tablet of biochemical differentiating enterobacteria (PBDE), NPO Diagnostic Systems” N. Novgorod.

1.2.3. Modeling the infectious process caused by E. coli 0157

The strain E.coli 0157: H7 N ° 212, which caused hemorrhagic colitis in children, was used in the work. The strain was obtained from the State Research Institute of Infectious Diseases of Japan, after identification at the Center for the Control of Infectious Pathogens (Tokyo).

Composition of toxins E.coli 0157: H7 N ° 212:

Exotoxin - VPA group

Stx Toxin - Stxl and Stx2

Lyophilized culture of strain E. coli 0157: H7 M ° 212 was scattered on Gause medium N ° 2 containing 5% sheep red blood cells, followed by incubation at 37 ° C for 16-18 hours. At the end of the incubation, the culture was washed off with a sterile isotonic sodium chloride solution and the number of microbial cells in 1 ml of suspension was calculated according to the optical turbidity standard.

To determine the LD ₅₀ for animals treated with the antibiotic, the culture was administered intraperitoneally to animals in a volume of 0.5 ml at concentrations of 0.25x10, 0.5x10 ⁷ , 0.75x10 ⁷ and 1x10 ⁷ OE / 0.5 ml; 0.25 x 10 ⁸ , 0.5 x 10 ⁸ , 0.75 x 10 ⁸ , 1 x ¹⁰ , 2.5 x 10 ⁸ , ⁵ x ¹⁰ ⁸ OE / 0.5 ml.

To simulate the infectious process, the culture of strain E. coli 0157: H7 Ν ° 212 was administered intraperitoneally at a previously determined concentration of LD ₅₀ . Infection of animals was carried out 24 hours after the end of antibiotic administration. 1.2.4. The introduction of an inactivated culture of strain E. coli 0157: H7 N °

212

Inactivation of the culture was carried out by heating it in a water bath for 45 min at a temperature of 100 ° C. An inactivated E. coli culture was administered to animals of three groups — those receiving antibiotic, PBS, and intact. The inactivated culture of E. coli was administered orally and intraperitoneally at concentrations of 1x10 ⁷ , 2.5x10 ⁷ , 5x10 ⁷ OE / 0.5 ml;

1x10, 2.5x10 OE / 0.5 ml. Three other, similarly formed groups of mice received per os and intraperitoneal culture in the same concentrations. PFR was administered per os to the control group of animals and intraperitoneally.

Analysis of the results was carried out daily for 7 days. based on the percentage of surviving / dead animals after the introduction of cultures. In addition, the clinical condition of the animals was taken into account.

1.2.5. The use of therapeutic drugs for the prevention and treatment of infections caused by E. coli 0157

In the course of the study, therapeutic protective preparations were introduced to study prophylactic and therapeutic efficacy in case of acute intestinal infections developing against the background of model dysbiosis. The introduction of drugs was carried out per os in 2 different doses - “human” and “mouse”, daily, 1 time per day, in a volume of 0.5 ml. To determine the prophylactic efficacy, the drugs were administered in two doses for 3 or 10 days before the day of infection. To determine the therapeutic efficacy, the preparations were started in two doses 24 hours after infection. The term of drug administration was 7 days.

Doses of protective drugs were:

I - in direct translation from the doses recommended for humans, using an increasing correction factor for mice ("human dose"): for lactulose - ЗОмгЛкг; for fructooligosaccharides - 200 mg / kg, for lignin - 100 mg / kg, for smectite - 100 mg / kg; for cocoa butter, the dose, depending on the composition of the preparations, was 180 mg / kg for preparations with lactulose and 250 mg / kg for preparations with FOS. II without the use of conversion factors (“mouse dose”) - respectively, was 20 times less.

results

Characterization of groups of animals with the introduction of antibiotics

At the first stage, the duration of doxycycline administration was

10 days Most animals in the experimental group receiving doxycycline at a dose of 0.4 mg had acute diarrhea, mice gained weight more slowly than animals of the control groups - intact or receiving PBS. In 20% of the animals of the experimental group, after the course of the administration of doxycycline, a decrease in body weight by an average of 10-12% was noted compared with the initial average weight, while in groups of animals treated with PBS and intact, the average body weight of the animals was 10 days increased by -10-15% compared with the original.

The mass of animals treated with doxycycline for 3 days remained stable. In animals of the control groups, the increase in weight was 3-5%.

In the experiment of modeling dysbiosis of mice with ampiox in animals, there was no death and negative dynamics of body weight, diarrhea was observed in 50% of animals.

Studies of the composition of the intestinal microflora

This study was aimed at studying the qualitative and quantitative characteristics of fecal microflora in laboratory animals. Table 8 presents the characteristics of fecal microflora in mice with simulated dysbiosis.

Table 8

When sowing suspensions of feces of a group of animals treated with an antibiotic, no growth of colonies of microorganisms was detected on an selective nutrient medium for isolation of staphylococci, and when sowing feces of intact animals on an environment for culturing enterobacteria. The number of lactobacilli and bifidobacteria in the samples obtained from animals from the experimental and control groups does not differ significantly (Table 8). On an elective medium designed to isolate p. Candida, there is a significant increase when seeding feces of a group of animals with simulated dysbiosis.

Characterization of Endo Colonies and Culture Identification

In connection with the presence of colonies on the Endo medium, when sowing fecal suspensions of mice with simulated dysbiosis and receiving PBS, these microorganisms were identified. Morphologically, two types of colonies were distinguished: small red colonies of regular shape with smooth edges and pale pink medium-sized colonies of irregular shape.

As a result of identification using a biochemical method of research, it was found that the selected cultures were: Kluyvera cryocrescens and Klebsiella oxytoca.

Determination of the infectious dose of E. coli 0157: H7 JV "212

According to the results of the experiments (Table 3) with the intravenous administration of E. coli 0157: H7 N ° 212 laboratory animals with experimental dysbiosis LD ₅ o was 2.5 10 ⁷ <LD ₅ o <5 10 ⁷ CFU. Based on the data obtained in experiments on the effectiveness of prebiotic preparations in vivo, the infectious dose of E. coli 0157 was 2.5 10 ⁷ CFU / 0.5 ml.

Determination of the preventive and therapeutic effectiveness of prebiotic drugs

Protective preparations, as well as control preparations (including the components of each product - lignin, smecta, fructooligosaccharide, lactulose) were injected into the animals after preliminary grinding through a special probe into the esophagus.

According to the experiment, as a result of both prophylactic and therapeutic administration of protective drugs, it was possible to reduce mortality in the corresponding experimental groups of animals with simulated dysbiosis (Table 9). In other groups of animals with dysbiosis, total death of animals was observed, with the exception of control groups: a group of mice that received PBS before infection, and a group without treatment with doxycycline (intact).

After infection, ~ 50% of the animals, both in the prophylactic and in the therapeutic groups, have impaired coordination, paresis of the hind limbs, and tremor. Animals are oppressed, inactive, the hair is ruffled, “icicles”. Mice developed diarrhea, especially in animals that received prophylactic doses. In some animals, urine and feces are not clotted blood (12 individuals). The peak mortality rate (up to 80%) occurs on the 4th day after infection. Table 9 shows the determination of the effectiveness of drugs when administered to laboratory animals after a 3-day administration of doxycycline.

Table 9

Note: the dose of E. coli 0157: H7 was 2.5 10 ⁷ OE

For prophylactic administration, “mouse” and “human” doses were used).

h - "human" dose

m - "mouse" dose The animals that received prebiotics (lactulose or fructooligosaccharide) in “mouse” and “human” doses begin to die first (within 48 hours), then animals of other groups. In the groups of mice treated with prebiotics and doxycycline without the subsequent administration of protective preparations, the lowest survival rate (about 20-30%) was revealed, which indicated a relatively low contribution of prebiotic effects to protecting animals from the toxic effect of the pathogenic strain of Escherichia coli 0157 .. The higher was the survival rate in groups of animals treated with enterosorbent therapy (lignin or smecta) is 40-50%. Efficiency for preparations in which the prebiotic was mixed with enterosorbent remained approximately at the same level. A composition of sorbents, prebiotics and fats provided the highest protection of animals from E. coli toxins - up to 80-90% of animals survived with preliminary administration of drugs (“prophylaxis”) and 100% observed protection with “therapeutic” administration of such compositions (simultaneously with pathogenic strain 0157.

EXAMPLE 6. Detoxification and normalization of microflora on the example of the use of the composition in the treatment of patients with symptoms of dysbiosis.

A comparative study of the clinical efficacy of a composition based on the enterosorbent of lignin, the prebiotic fructooligosaccharide and cocoa butter or its substitute in the complex treatment of bacterial intestinal infections in children, the effect on the biochemical parameters of endotoxemia and intestinal microbiocenosis. The study included 30 children aged 5 years to 12 years who received treatment for acute intestinal infections (AII) of a bacterial nature; however, the etiology of the disease is established in 56% of children. Salmonellosis prevailed in the structure of verified intestinal infections (70% of children), bacterial dysentery was recorded in 30% of cases. The vast majority of children (75%) suffered a moderate form of acute intestinal infections, 15% of patients had a severe form, and 10% had a mild infection. Children entered the first 3 days from the onset of the disease. Symptoms of intoxication and damage to the gastrointestinal tract of varying severity were observed in all cases.

By random sampling, 2 groups of children were formed that are representative by age, etiology, and severity of the disease. The first group consisted of 15 children who received a preparation based on the composition (according to Example 1) of lignin enterosorbent (350 mg) with the addition of lactulose prebiotic (150 mg) and cocoa butter or its substitute (500 mg) (a preparation in the form of lozenges for chewing), hereinafter referred to as the Composition. The drug was given to patients twice a day in the amount of 1 lozenge for children under 10 years of age and 2 lozenges three times a day for children over 10 years of age. The duration of admission was 7 days. The second group included 15 patients who received the well-known Lactofiltrum preparation (dietary supplements containing a composition of lactulose (PO mg) and hydrolytic lignin (350 mg)) in the same dosage regimen in the acute period of infection.

Analyzing the course of the disease, a significant reduction in the duration of intoxication syndrome was found in the group of children receiving the composition (3.3 ± 0.2 versus 4.9 ± 0.7 days in the second group, p <0.05), a clear tendency to reduce the febrile period ( 2.5 ± 0.4 versus 3.8 ± 0.7 days). The duration of the local syndrome also depended on the therapy option and was characterized by a faster relief of flatulence and abdominal pain in the first group of children (2.4 ± 0.3 and 1.8 ± 0.2 days, respectively), whereas in the control group of children these symptoms were recorded 5.3 ± 1, 2 and 2.7 ± 0.6 days, respectively. The duration of diarrhea did not have significant differences in the compared groups, however, the visualization of pathological impurities in the stool during therapy was significantly reduced by the Composition (4.0 ± 0.4 versus 7.6 ± 1.1 days in the second group, p <0.05).

Laboratory screening, in addition to generally accepted methods, included the determination of biochemical markers of endogenous intoxication: low and medium molecular weight substances (VNSSM) in blood plasma and red blood cells and their ratio (distribution coefficient). The established increase in plasma VNSSM in the acute period of the disease was observed in both groups of children (13.7 ± 1, 5 and 13.6 ± 1, 8 UE with a norm of 7.9 ± 0.8 UE). At the same time, the level of VNSMM of erythrocytes remained at the upper limit of normal values, reflecting the sorption capabilities of the erythrocyte membrane. The distribution coefficient in both groups increased due to an increase in the pool of endogenous metabolites in blood plasma. The dynamics of the indicators of endogenous intoxication in the compared groups (see Table 10) showed that the use of the Composition in the complex treatment of acute intestinal infections contributes to the normalization of VNSSM plasma and distribution coefficient by the 5th day of treatment (8.6 ± 0.8 UE and 0.3 ± 0 , 04, respectively). At the same time, in the comparison group in patients, the circulation of endogenous metabolites is prolonged, which is reflected by the persistent high values of VNSMM in plasma (12.8 ± 1, 3 UE, p <0.05) and distribution coefficient (0.5 ± 0, 05). Table 10 shows the dynamics of indicators of the level of endotoxemia.

Table 10

VNSMM LAL test

VCSM plasma

erythrocyte group diagnosis

BEFORE before before after before after dysentery Experience 15.12 6.43 26.02 25.38 3 3 dysentery Experience 9.18 5.53 29.57 20.14 3 3 dysentery Experience 17.33 12.6 30.49 29 , 68 1, 25 2.5 dysentery Experience 12.58 12.29 27.74 25.54 3 3 dysentery Control 14.74 1 1, 18 26.89 27.62 1.25 1.25 dysentery Control 7.12 10.47 29.88 22.72 2 2 dysentery Control 8.67 1 1.02 23.83 22.07 3 3 dysentery Control 6.25 7.91 26.45 20, 16 3 3 salmonellosis Experience 16.44 9 , 2 24.06 23.09 1, 25 1, 25 salmonellosis Experience 1 1, 4 5.73 26 19.94 2.5 1, 25 salmonellosis Experience 19.4 1 5.02 24.23 23.7 1, 25 1.25 salmonellosis Experience 21, 37 7.95 25, 13 23.95 3 2.5 salmonellosis Experience 17.06 8.59 22.94 21, 12 2.5 1.25 salmonellosis Experience 15.38 1 1, 35 26.57 19.44 2.5 1, 25 salmonellosis Control 1 1.28 9.86 30.37 31.33 2.5 2.5 salmonellosis Control 18.33 19, 15 24.54 25.04 3 2.5 salmonellosis Control 1 1.56 12.38 28.13 28, 23 2.5 3 salmonellosis Control 14.82 10.49 31.24 29.72 1.25 2 salmonellosis Control 14.25 9.7 23.38 24.83 1.25 1.25 salmonellosis Control 12.73 1 1.75 22.4 26.56 1.25 1.25 salmonellosis Control 1 1.42 8.22 22.67 21.24 1.25 2.5

g / e Experience 1 1, 97 9.14 27.18 25.24 2.5 2 unspecified

g / e Experience 20.67 8.37 26.28 25.87 1.25 2 unspecified

g / e Experience 10.86 7.86 27.15 28.72 2.5 1.25 unspecified

g / e Experience 16.28 9.56 24.89 24.19 2.5 2.5 unspecified

g / e Experience 19.88 14.23 30.6 27.15 2.5 1.25 unspecified

g / e Control 23.69 7.66 28.44 28.7 2.5 2.5 unspecified

g / e Control 1 1.28 9.22 28.14 25.83 1.25 2.5 unspecified

g / e Control 18.05 17.96 22.41 23.43 2 2 unspecified

g / e Control 12.32 26.1 1 24.46 23.57 3 3 unspecified

NOTE: the norm of the content of endotoxins in the blood is 1.25 o. e. The use of the LAL test made it possible to establish that at the beginning of the observation, 2/3 of all patients recorded an increase in the level of endotoxins in the blood plasma (which indicated "overcoming" the pathogenic protective barriers of the body. There is a correlation between the severity of clinical symptoms of intoxication in patients and an increase in endotoxin concentration.At the same time, with relatively mild forms of intoxication (mainly salmonellosis), the initial levels of endotoxinemia were lower or absent. During the treatment process, it was shown that even for a rather short period of taking the drug, the Composition observed, on average, a decrease in the concentration of endotoxins in the blood plasma, however, this phenomenon is more characteristic for cases of treatment of salmonellosis, whereas with dysentery this indicator did not reveal a significant decrease, as in cases of a more severe course of other forms of infections. It should be emphasized that the period of observation of patients in the hospital is insufficient to achieve normalization of the intestinal microflora due to the prebiotic included in the composition, the duration of which should be at least 10-14 days.

In general, the test results confirmed the presence of a significantly more pronounced therapeutic effect of the Composition in the early stages of treatment of acute intoxication of infectious genesis compared with a drug that did not contain a base in the form of cocoa butter, and allowed us to recommend an extension of the time for taking this type of drug to two to three weeks in order to ensure restoration of the intestinal microbiocenosis disturbed by the infection (and the possible administration of antibacterial drugs).

EXAMPLE JYs7 Prebiotic Activity Study

To study the prebiotic effect of the claimed composition and confirm its suitability as a biologically active food supplement (BAA) for correcting the microflora composition impaired after antibiotic therapy, we studied their effect on the state of intestinal microbiocenosis in children.

Under observation were 28 children aged 5 to 14 years who had severe symptoms of intestinal dysbiosis that developed in 12 patients - after taking antibiotics in the treatment of acute intestinal infections; in other patients, dysbiosis developed in connection with other diseases of the gastrointestinal tract - impaired intestinal motility (irritable bowel syndrome), impaired bile secretion (functional dyskinesia of the biliary tract), impaired secretion of digestive enzymes (pathology of the pancreas and duodenum.

As a means of correcting the composition and activity of the intestinal microflora, the claimed composition was used, made in the form of a biologically active additive in the form of a troche (composition according to example N ° l). Children were prescribed the drug in the amount of 2 lozenges twice a day for 14 days. Drugs were given one hour before meals. During the test, no child refused to take the drug. Assessment of the intestinal microflora of patients was carried out by the method of bacteriological control in combination with analysis of the spectrum of fatty acids in stool samples. The degree of dysbiosis was established in accordance with the current OST 91500.1 1.0004-2003 (Protocol for the management of patients with intestinal dysbiosis).

Clinically evaluated the effect of drugs on the general condition of patients, physical activity, and on the severity of the manifestations of the main symptoms of dysbiosis: pain in the abdomen, flatulence, stool frequency and consistency of feces.

Improving the nature of the stool was observed in 25 of 28 children. In 3 children the stool remained unchanged.

A positive change in the composition of the intestinal microflora was observed in all 28 children. Moreover, dysbacteriosis of the 3rd degree was observed in 6 children, the 2nd degree in 13 children and the 1st degree in 9 children. The degree of dysbiosis decreased by 1-2 steps.

The taste qualities of the drug as “tasteless” were evaluated by 6 children, 19 children identified taste qualities as “tolerant” and 3 children called the drug “tasty”.

The staff and parents rated the use of the drug as “convenient” in all cases.

No side effects have been reported.

The conclusion of experts.

Based on the data obtained, we can assume that the drug

Fructofiltrum in lozenges has a pronounced positive effect on the state of intestinal microbiocenosis in children, has acceptable

(taste and method of use) for pediatric clinical practice, characteristics as a dietary supplement for long-term use.

EXAMPLE Γ »8 Treatment of gastroenteritis of viral etiology in children Studies were carried out on the basis of the infectious diseases department of the Children's City Clinical Hospital. Under observation were 20 patients with moderate forms of acute viral etiology of the osmotic etiology type of diarrhea at the age of 3 to 10 years. Upon admission to the hospital, all patients received routine laboratory tests.

The scope of laboratory tests: a general blood test, urinalysis, a blood cell count, a feces analysis for helminth eggs, a bacteriological study of bowel movements in the intestinal group of bacteria, a study of coprofiltrate for the presence of antigen of the mouth and adenovirus, as well as PCR for the presence of norovirus RNA in coprofiltrate.

Age of patients

Patients were admitted to the hospital on the 1st (6th) or 2nd (4th) day of the disease in a moderate state with mild symptoms of intoxication, toxicosis with exicosis of the 1st degree. In all patients, the onset of the disease was acute with an increase in body temperature to 37.4 - 38.0 ° C (5) and from 38.1 to 38.5.0 ° C (5). Simultaneously with an increase in body temperature, all patients experienced repeated vomiting from 5 to 15 or more times / day (on average 9.5 times / day) and plentiful watery stools without pathological impurities 5-8 times / day (on average 6.8 times / day). All patients, upon admission to the hospital, also experienced flatulence (independent or palpation rumbling in the abdomen, etc.) and abdominal pain associated with increased gas formation.

All patients received standard basic therapy upon admission to the hospital: a rational diet, enzyme preparations (mesim forte), oral rehydration and, if indicated, symptomatic drugs (antipyretic, antiemetic).

The results of a bacteriological study of bowel movements in the intestinal group - in all patients were negative. The viral etiology of gastroenteritis was confirmed by X-ray analysis and PCR diagnostics in 14 (70%) patients, of which 8 were rotavirus and 6 patients had norovirus infection.

All patients were randomly divided into two groups of 10 children. One group (experience) was prescribed the composite drug “Filtrum- Safari ”(in one lozenge for chewing lignin 255 mg, fructooligosaccharides 1,100 mg and cocoa butter 1350 mg) (the product is made in accordance with example N ° l). Patients in the control group were prescribed the Lactofiltrum dietary supplement comparison drug (dietary supplement tablets containing the composition of lactulose (1 10 mg) and hydrolytic lignin (350 mg)).

The drugs were taken by patients for 5 days. The main results of clinical observation (the dynamics of relief of the main symptoms of acute intestinal infections) are presented in table 1 1. Table 1 1.

Thus, when the drug “Filterum-Safari” is included in the basic therapy according to the claimed composition, in the treatment of gastroenteritis of viral etiology in children it was found that clinical recovery in most cases (80%) occurs already on the 3rd day from the start of treatment, and on the 4th day - in all patients. The average duration of the acute period of the disease was 2.4 days.

It was also established that the new dosage form of the enterosorbent lignin has a fairly pronounced detoxification effect. Symptoms of intoxication in most patients (80%) completely stop already on the 2nd day of treatment, including at the same time in 80% of patients lethargy disappears, and in all patients (100%) - decreased appetite and fever. On the 2nd day of treatment - all vomiting stops, abdominal pain disappears. At the same time, stopping the phenomena of flatulence occurs only on the 3rd day, and the frequency and nature of the stool normalize on the 4th day of treatment. Overall, in 8 (80%) of 10 patients, the clinical effect was "excellent" - clinical recovery occurred on the 3rd day of treatment. A good clinical effect occurred in 2 (20%) patients - clinical recovery occurred before the 5th day from the start of treatment.

No adverse reactions have been identified. However, in some cases, children paid attention to the "unpleasant" taste of the drug and nausea after taking it

Compared with the well-known drug “Lactofiltrum”, the dynamics of resolution of pathological symptoms is much higher, on average, normalization occurs 1-1.5 days earlier.

EXAMPLE 9. The effect of the composition on lipid metabolism

The effect of the drug based on the composition of insoluble dietary fiber, prebiotic and cocoa butter (or its substitute) was studied in

outpatient conditions in a group of patients with diseases of the cardiovascular system, in particular in patients with angina pectoris in combination with arterial hypertension.

The study included patients with metabolic syndrome (metabolic syndrome was diagnosed on the basis of age over 39 years, moderate arterial hypertension (AH), body mass index (BMI) of more than 25 kg / m, hypertriglyceridemia and low HDL content). We examined 34 patients aged 46 to 67 years, of which 18 were women and 16 were men. They were divided into two groups of 17 people each. All patients followed a low-calorie diet (8 tables) and received antihypertensive therapy (ACE inhibitors). Patients of the first group in addition to the main treatment received the drug "Fructofiltrum" (hydrolytic lignin 250 mg, dietary fiber “Vitatsel” 150 mg, fructooligosaccharides 1000 mg, cocoa butter 1250 mg) in the form of lozenges for chewing 2 lozenges 2 times a day 1.5 hours before meals. The duration of admission was 21 days.

The second (control) group of patients on the background of standard therapy took the comparison drug - a fixed composition of dietary fiber and the Lactofiltrum prebiotic (hydrolytic lignin 275 mg, lactulose 1 10 mg). Patients included in the study did not take other

lipid-correcting drugs.

The results of evaluating the effectiveness of the use of the Fructofiltrum composition in patients with dyslipidemia (see Table 12) showed that taking the drug for 3 weeks already led to a significant change in lipid metabolism in most patients in the main group. So, in 13 of 17 patients, the content of total cholesterol (OXC) decreased by 18.5%, and in 9 cases, OXC decreased to normal values. More noticeable changes occurred in relation to the content of triglycerides. In the group as a whole, the level decreased, on average, by 19.5% (p <0.01), and in 13 patients the triglyceride content was reduced to normal values. Taking the drug even more effectively affected the content of cholesterol-VLDL, the level of which in the group as a whole decreased by 31.4%. Moreover, this indicator significantly decreased in 15 patients. The level of HDL-C in 13 patients increased by more than 1.6 times. In 14 patients, a decrease in the atherogenic index by 21.5% was noted.

In the control group, overall positive changes in biochemical parameters were also recorded, however, these changes were less pronounced and did not reach values significantly different from the initial ones.

The indicators are shown in table 12.

VLDLP, mmol / L 0.86 ± 0.08 0.52 ± 0.04 0.56 ± 0.08 0.44 ± 0.02

HDL, mmol / L 1, 02 ± 0.03 1, 63 ± 0.07 * 1.26 ± 0.04 1.46 ± 0.05

Atherogenic index 5.1 ± 0.64 3.7 ± 0.46 * 4.42 ± 0.72 4.2 ± 0.72

CRP, mg / ml 8.95 ± 1, 40 5.8 ± 0.66 * 7.62 ± 1, 12 3.6 ± 0.48 *

The effect was noted with all types of dyslipoproteinemia according to Fredrickson; its greatest activity was established with the P subtype. In patients of the 1st group with insufficient clinical effect and in patients of the 2nd (control) group, changes in lipid metabolism were less favorable. The dose of prolonged-acting nitrates taken during treatment decreased, on average, by 1.5 times, and nitroglycerin intake from 4-6 to 1-2 tablets per day.

Thus, the Fructofiltrum composition, prescribed for patients with coronary artery disease for 3 weeks, 2 lozenges 2 times a day, is most effective in patients with atherogenic P type dyslipidemia, lowering the levels of TG, cholesterol-VLDLP, IA and increasing the content of HDL-C. The results of evaluating the clinical effectiveness of the drug depending on the degree of hypercholesterolemia showed that its effects were expressed by a decrease in the number of angina attacks. So, before treatment, its frequency was 7.2 ± 1, 5 times a week, after 3 weeks - 6.0 + 1, 2 (p <0, 1). In 14 out of 16 patients of the main group with initial arterial hypertension, the administration of the Fructofiltrum preparation helped to reduce headache, increase working capacity, and improve sleep and memory. In patients with stable angina pectoris of P-III FC in all indices, statistically significant positive shifts occurred in the form of a decrease in atherogenic and an increase in antiatherogenic indicators. A decrease in the severity of clinical manifestations of coronary insufficiency in 73% of patients was accompanied by positive dynamics on the ECG. Most patients subjectively noted increased exercise tolerance. Thus, even fairly small doses of the studied composition against the background of traditional IHD therapy in combination with a hyponatrium, lipid-lowering diet contribute to the correction of the lipid spectrum of blood serum and the fatty acid composition of membrane structural lipids by affecting the synthesis of lipoproteins in patients with coronary heart disease, hyperlipidemia and hypertension . From the above examples, it can be reasonably concluded that the claimed composition is an effective and safe biologically active drug for cleansing the body of toxins and normalizing microflora, with the property of dissolving and absorbing fat-soluble (hydrophobic) toxic molecules, along with high sorption of amphiphilic (including endotoxins of bacteria) and hydrophilic toxic substances throughout the gastrointestinal tract, starting with the oral cavity; while the composition has a normalizing effect on the disturbed microbiocenosis of the digestive tract, inhibiting the growth and reproduction of extraneous microflora and thereby providing a preventive effect. Important is the fact that the composition is not utilized by pathogenic microflora.

The combination in one composition with the specified content of the components of the prebiotic (in particular fructooligosaccharides or fructooligosaccharides together with lactulose), sorbent (in particular lignin), as a substance with a predominant affinity for hydrophilic and amphiphilic toxic molecules and bacteria, with cocoa butter (or its substitutes ), which has the additional property of dissolving and absorbing fat-soluble (hydrophobic) toxic molecules in the entire gastrointestinal tract, starting from the oral cavity in an effective thin-emulsion form, as well as giving hepatoprotective properties (strengthening the structure of the membranes of liver cells and lowering the content of endogenous metabolic toxins in the blood and cells, the property of inhibiting the growth and development of pathogenic microorganisms, which has the ability to increase the body’s immunity and promote the absorption of calcium in the intestine and reduce the effects of osteoporosis, allowed to obtain a drug with fundamentally new properties that have the ability to bind throughout the digestive tract and remove pathogenic microorganisms: bacteria, yeast, fungi and viruses, and other harmful organisms, while not harming friendly bacteria, to strengthen immunity, increase the effectiveness of treatment of infectious intestinal diseases, reduce the risk of developing cardiovascular diseases (including due to the binding of excess cholesterol) while improving the consumer characteristics of the drug, in the form and composition suitable for use by children, from the age of 3-5 years.

Industrial applicability

The present invention is implemented using universal equipment widely distributed in the food industry.

Claims

Claim

1. A composition for cleansing the body of toxins and normalizing microflora, containing at least one insoluble enterosorbent, cocoa butter and prebiotic, and enterosorbent and prebiotic used in the form of a powder with a particle size of not more than 65 microns, with the following content of components, in mass %:

- enterosorbent 3-50%;

- cocoa butter 5-60%;

- prebiotic 3-50 mass%.

2. The composition according to claim 1, characterized in that the insoluble enterosorbent is an insoluble dietary fiber from the group: lignin, vegetable fiber, bran, cellulose and its esters, microcrystalline cellulose, highly esterified insoluble pectin, or mineral from the group: zeolite, smectite , silica (silicon dioxide), activated carbon.

3. The composition according to claim 1, characterized in that it contains substitutes for cocoa butter and / or substitutes for cocoa butter, coconut oil, palm kernel oil or a combination thereof with other fats ..

4. The composition according to claim 1, characterized in that it contains a prebiotic in the form of an oligosaccharide from the group: lactulose, lactitol, fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, maltooligosaccharides, inulin, arabinogalactan, isomalt.

5. The composition according to any one of claims 1 to 4, characterized in that it contains enterosorbent with a moisture content of not more than 5 mass%.

6. The composition according to any one of claims 1 to 4, characterized in that it further comprises at least one flavoring additive, mainly food flavoring, or a flavor corrector.

7. The composition according to any one of claims 1 to 4, characterized in that it further comprises at least one natural or identical to a natural food coloring in an amount of not more than 3 wt.%.

8. The composition according to any one of claims 1 to 4, characterized in that it is made of a homogeneous consistency in solid form.

9. The composition according to claim 8, characterized in that it contains lecithin in an amount of not more than 1 mass% as an emulsifier.

10. The composition according to p. 9, characterized in that it is made by casting the melt into molds.

1 1 The composition according to p. 8-10, characterized in that it is made in the form of a lozenge (tile, bar) of any form technically feasible during casting, for example, oval, round, rectangular, square or in the form of nuts, coffee beans figures of animals or fish or the like.

12. The composition according to any one of p. 1-4, characterized in that it is made of a homogeneous consistency in a paste form.

13. The composition according to p. 12, characterized in that it contains, as a diluent, an auxiliary substance of liquid paraffin in an amount up to 20 mass%.