RU2473347C1 - Prebiotic composition for normalising body microflora - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents a composition for normalising body microflora containing at least 3 prebiotic substances taken of four groups of prebiotic with various molecular chain lengths: monomer prebiotics (number of chains 1); dimer prebiotics (number of chains 2); oligomer prebiotics with number of chains 3 to 10; polymer prebiotics with number of chains more than 10; with the ingredients of the composition found in certain proportions, wt %.

EFFECT: invention provides recovery, maintaining of the qualitative-quantitative formula and activation of bacteria of various geni of normal intestinal microflora for adequate implementation of the microbiocenosis function along the full length of the digestive tract starting from an oral cavity and an oesophagus to a lower large intestine, as well as recovery of microbiocenosis of the other intestines.

16 cl, 12 ex

Description

The invention relates to a composition containing prebiotics, designed to normalize the composition and functions of the natural microflora of humans and animals and can be used for the preparation of medicines, food products, cosmetic products or animal feeds.

Various organs and cavities of the human body, together with their natural microflora, represent a single ecological system - microbiocenosis. Normal microflora is a complex association of bacteria, fungi, viruses and other microorganisms. Normoflora microorganisms carry out vital functions for humans: protective, digestive, trophic, energetic, cleansing (detoxification), antimutagenic, immune, etc.

Prebiotics are substances that have a selective stimulating effect on the reproduction, growth and functional activity of microorganisms of the natural (normal) microflora of a person, primarily the normoflora of the digestive tract (NPT). Prebiotics perform the functions of selective stimulation and restoration of the abundance and activity of the normal / natural bacterial microflora of the digestive tract. Indirectly due to this, such effects are realized - improving digestion, normalizing the regularity and lightness of stools, improving the condition of the liver, spleen, pancreas, small and large intestines, eliminating dysbiosis and its manifestations, improving the absorption of calcium (maintaining bone density) and other macro- and trace elements, improve metabolism, improve cholesterol metabolism, improve immunity, lower blood sugar in diabetes, reduce excess weight and much more.

The most studied group of prebiotics is the group of carbohydrate prebiotics, which are carbohydrates consisting of one, two or more molecules connected by beta-glycosidic bonds. The absence of betaglycosidases in the enzyme system of the human digestive system, that is, enzymes that break down such bonds, makes prebiotics indigestible (digestive enzymes) carbohydrates. Prebiotics, not being digested and not absorbed in the upper digestive tract (PT), are split (hydrolyzed and absorbed) exclusively by the NTP and thus act as a selective nutritional growth factor for normoflora.

It is known to use prebiotics to improve, supplement, expand the consumer characteristics of a well-known product - milk drink, chocolate, ice cream, cheese (WO 2008152472), nutrient mixture / composition (RU 2268069, CA 2741554, US 2010105615, WO 2004017979), sweetener / sweetener (RU 2008123261), including to reduce the side effects of the main active substances or as a filler.

In these products, prebiotics are used in concentrations insufficient to meet the recommended daily requirements for prebiotic substances, i.e. they are used not for the targeted effect on the NTP, but for the concomitant effect on the main active substance. Therefore, in these products, their own prebiotic properties are not fully realized and in the required volume, through which a versatile healing effect on human and animal organisms is carried out.

The disadvantage of the invention (RU 2009116836), which uses a combination of enterosorbent and prebiotic, is that the prebiotic stimulates the production of their natural metabolites by bacteria - organic acids, vitamins and other important and bioregulatory substances. And enterosorbent, due to its lack of selective sorption activity, absorbs these metabolites of normoflora and removes them from the body. Thus, the sorbent reduces the effect of the prebiotic, at least in the lower parts of the small and upper parts of the large intestine, until all pores of the sorbent are filled.

The disadvantage of the invention according to the patent US 7618951, 2009 is that to solve the particular problem of the treatment of type 2 diabetes, prebiotics with a narrow range of polymerization from 2 to 10 (preferably between 3 and 8) are used as additional components, and prebiotics with long and branched chains. This does not allow the full use of the full potential of NTP (especially the lower parts of the large intestine) and its various representatives.

The present invention allows the restoration, maintenance of qualitatively-quantitative composition and activation of bacteria of various genera of NPT for the full realization of the functions of microbiocenosis throughout the digestive tract, starting from the oral cavity and esophagus to the lower parts of the large intestine; as well as to restore microbiocenosis of other parts of the body.

The selection of prebiotic substances in a balanced composition is carried out in accordance with their systematization along the chain length (the number of monomer units in the prebiotic molecule) to obtain an effect on a specific section of the digestive tract.

So, monomeric prebitics (number of units 1) begin to show effect from the oral cavity and esophagus. Dimeric prebiotics (number of links 2) begin to show effect from the level of the stomach and small intestine. Oligomeric prebiotics (with the number of links from 3 to 10) - show an effect in the small intestine and upper parts of the large intestine. Polymeric prebiotics (with a number of units of more than 10) exhibit an effect from the upper sections to the lower sections of the large intestine. The combination of different types of prebiotics allows you to create balanced prebiotic complexes for direct use, as well as target products based on them to obtain accented effects in relation to certain organs and systems (for the heart, immunity, liver, etc.).

If, when preparing a prebiotic composition, preference is given to substances of a single or similar type — along the chain length, then the product created in this way can lead to the activation of normoflora homogeneous in the enzymatic activity of microorganisms in a limited part of the digestive tract, which, accordingly, will be reflected in the limited set of biochemical and physiological effects this part of the microbiocenosis. When using “uniform” prebiotic complexes, another microflora with a different set of biological effects within the symbiosis and in relation to the host microorganism will not proportionally develop.

When compiling a prebiotic complex, it is necessary to ensure the diversity of the prebiotic substances in the chain structure, which accordingly will ensure the restoration of a wider spectrum of bacteria of the microbiocenosis and an expanded number of biological tasks performed by them, both within their own association and for the macroorganism.

The described approach solves the problem of prevention and maintenance of normoflora - more diversified and balanced, without endomycrobiocenotic distortions.

Prebiotics cannot realize their entire arsenal of positive effects in a short time (single doses or course for several days), because the vast majority of their effects are associated with the restoration, restructuring, increase and stabilization of the functional activity of the normoflora PT (for example, the restoration of vitamin synthesizing activity or enzymatic activity against certain prebiotic or difficult to utilize substrates). Similar effects begin to appear only after 10-20 days of regular use of prebiotic complexes. However, long-term courses of prebiotics cannot carry the potential threat of delayed side effects. In this regard, the duration of the use of prebiotics should be at least 10 days. The most optimal is the inclusion of balanced prebiotic complexes in the daily diet. Balanced prebiotic complexes are indicated for everyday use for all population groups (for health reasons, nutrition, age, etc.).

When studying the effect of prebiotic complexes on the restoration of microbicenosis of the digestive tract, oral cavity, skin, and mucous membranes, it was found that for a versatile prebiotic-healing effect, the composition of the prebiotic complex should simultaneously include at least three prebiotics that differ in chain length (the number of monomeric units in molecule).

Prebiotic complexes should be convenient for use in the daily diet, for which the composition of the complex includes excipients to improve the taste, appearance, aroma and to obtain finished products and expand the arsenal of methods of application. The total content of prebiotic components in the complex should be at least 50 wt.%.

The daily dose when taken by mouth should be 5-20 g per day, which is an average of 15-60% of the recommended daily intake of prebiotic substances in the human diet. This is enough to replenish the diet with prebiotics and compensate for their deficiency in the typical structure of modern nutrition. The duration of the course is not limited, but is at least 10 days.

To obtain problem-oriented prebiotic complexes, it is effective to use extracts and other extracts from plants or other sources (microorganisms, beekeeping products, etc.) containing biologically active substances of this source together with prebiotics. For example, hawthorn extract contains prebiotic polysaccharides and flavonoids that are conducive to heart function. Therefore, the prebiotic complex containing the extract of polysaccharides and flavonoids of hawthorn will contribute to the improvement of the cardiovascular system.

Similar approaches are used in the preparation of prebiotic complexes for skin, hair, oral mucosa, and external genitalia.

Example 1

Structure: Mass fraction,% Xylitol (monomeric prebiotic) 15.0 Lactulose (dimeric prebiotic) 20,0 Oligofructose (oligomeric prebiotic fructan) 25.0 Resistant Starch (Polymer Prebiotic Polyglucan) 25.0 Apple pectin (polymer prebiotic methylgalacturonate type) 10.0 Excipients: Dry powder of berries (in the assortment of raspberries, currants, cherries, etc.) 4.0 Lemon acid 0.9 Sweetener 0.1

As components of the complex, prebiotics with different chain lengths were used, for prebiotic stimulation of the maximum number of bacteria of the NTP in different parts of the digestive tract.

Xylitol is used as a monomeric prebiotic to provide a prebiotic effect in the oral cavity, esophagus and stomach.

Lactulose (4-O-beta-D-galactopyranosyl-D-fructose) is a disaccharide consisting of residues of galactose and fructose molecules, a synthetic stereoisomer of milk sugar - lactose. Resistant starch and pectin were used as polysaccharide prebiotics.

The complex in the form of a powder or granules can be used directly with water or another drink. You can also enter into the composition of culinary dishes (cereals, desserts, fruit salads, etc.). The product has a sweet and sour taste.

Product Application Results

The product was used in a sanatorium as a functional food product for inclusion in the diet of people with a pronounced problem of stool regularity (with a diagnosis of chronic constipation, microbiological methods showed a violation of the intestinal microflora, expressed in a reduced number of bifidobacteria less than 10 ⁹ per g). The test group consisted of 15 people aged 35 to 65 years, the control - 10 people of the corresponding age. The test group took a product of 5 g 3 times a day by dissolving a portion of the product in water or juice and eating it during breakfast, lunch and dinner. In the 14 people of the test group during the first week there was an improvement in digestion, restoration of stool regularity and easier bowel movements. One person from the control group had flatulence in the first days, it was recommended to him to reduce the frequency of use to once a day. A week later, he began to take the product in general mode and there was no longer any discomfort. After 10 days of regular inclusion of the product in the diet in the test group, the indicators of regularity, ease of defecation, and stool structure (consistency, volume, color, smell, composition) were restored to the norm. Microbiological control showed restoration of the intestinal microflora composition and an increase in the titer of bifidobacteria to 10 ¹¹ per g. In the control group, there were no marked improvements, physiological and microbiological, similar to the test group. Thus, the healing effect of the product, manifested in the restoration of peristalsis, regularity and characteristics of the stool, as well as the restoration of the composition of the microflora of the digestive tract, indicates the normalizing effect of the product on the composition and functions of the microflora of the digestive tract.

Example 2. Prebiotic complex with additional bacteriogenic effect.

Structure: Mass fraction,% Lactitol (dimeric prebiotic) 25.0 Oligofructose (Oligomeric Prebiotic Betafructan) 25.0 Guar gum (polymer prebiotic like galactomannan) 15.0 Hyaluronate (a polymer prebiotic such as glucosaminoglycan) 15.0 Apple pectin (polymer prebiotic methylgalacturonate type) 15.0 Excipients: Simethicone 2.0 Calcium stearate 1,0 Aerosil 1,0 Lemon acid 0.9 Sweetener 0.1

In bacteria of the genus Bacteroides, in comparison with bifidobacteria and clostidia, the arsenal of enzymes such as alpha and beta N-acetylglucosaminidases and hexosaminidases is wider. Therefore, acetylated glycoproteins, glycolipids, branched hetero-polysaccharides should be attributed to selective prebiotics for Bacteroides. For example, glucosaminoglycans, previously called mucopolysaccharides, such as chondroitin sulfate, derivatives of hyaluronic acid, keratin (keratan) sulfate, etc.

Molecules of glycosaminoglycans (mucopolysaccharides, mucus) consist of repeating units that are composed of residues of uronic acids (D-glucuronic or L-iduronic) and sulfated and acetylated amino sugars.

These carbohydrate groups should be assigned to the group of prebiotic derivatives, as they differ from the initial (“basic”) prebiotics by the more complex structures of monomeric carbohydrates that build the chain of the oligomer or polymer of the prebiotic, as well as by the presence of a large number of branches of the polymer. The original complex monomer units can be presented in the form of amino sugars or sulfated forms or in the form of ethers or esters, respectively, with organic alcohols or acids. These “complicated monomeric” carbohydrate units, as well as the initial (“simple”) carbohydrates, are assembled using beta-glyosidic bonds into oligomeric or polymeric structures. This certain “complexity” and cumbersomeness of the monomer and branching of the polymer does not change their most important property, which determines their prebiotic effect - the possibility of cleavage of these bonds and assimilation of carbohydrates by the normal flora of the body. However, the number of representatives of normoflora capable of digesting and realizing the potential of these forms of prebiotics is more limited. Thus, a variant arises of a certain selectivity and selectivity of the prebiotic effect, when these derivatives of prebiotics activate and normalize the work of representatives of the genus Bacteroides, some types of bifidobacteria and propionic acid bacteria capable of transforming their enzymatic activity to this structural “complexity” of the prebiotic. These characteristics of prebiotic derivatives allow the creation of prebiotic compositions that selectively restore certain groups of microorganisms of normal flora and their specific functions. For example, representatives of the genus Bacteroides are involved not only in the processes of fermentation of carbohydrates and protein utilization, but also in biotransformation, metabolism of steroids - bile acids, steroid hormones, cholesterol, etc.

The group of derivatives of prebiotics is widely represented in nature (for example, as part of plant mucus, pectins) or can be obtained using chemical and biochemical technologies for the transformation of the initial prebiotics.

Guar gum is a neutral polysaccharide galactomannan, consisting of mannose and galactose.

Lactitol is a prebiotic disaccharide consisting of galactose and sorbitol connected by a beta (1-4) bond.

One of the possible side effects at the initial stages of taking prebiotic complexes may be flatulence (increased gas formation). Due to the action included in the composition of simethicone, manifestations of flatulence are eliminated.

The complex in the form of tablets is used as a dietary supplement for food as a general strengthening agent that reduces the manifestations of irritable bowel syndrome, improves peristalsis, and restores stool regularity.

Before use, the complex in the form of a powder is poured with warm water for 5-15 minutes at the rate of 5 g of powder in half a glass of water, periodically mixed until jelly is obtained. Eat as a dessert.

Product Application Results

The product was used 5 g 2 times a day for 10 days for people with high cholesterol (hypercholesterolemia, total cholesterol, borderline and elevated in the range of 200-320 mg / dl), with a tendency to form gallstones and impaired bile duct function (biliary dyskinesia). At the same time, 7 out of 21 people from the test group (age from 40 to 65 years) had concomitant dermato-cosmetic problems with the skin condition - increased dry skin, cracking of the skin in the elbows, heels, presence of age spots, including on the face.

After 10 days, the average indicators of total cholesterol in all patients were 170-250 mg / dl, that is, they switched to the level of normal and border indicators. There was an improvement in overall well-being, a decrease in discomfort in the liver and biliary tract, and an improvement in digestion. In patients with concomitant cosmetic problems, after 10 days there was a decrease in the sensation of dryness and tightness of the skin, after 3 weeks the cracking of the skin stopped, after 2 months of regular use, the color intensity of pigment spots on the face and body significantly decreased.

Example 3. Prebiotic complex with additional eubacteriogenic and clostridiogenic effect

Structure: Mass fraction,% Maltitol (Monomeric Prebiotic) 15.0 Lactitol (dimeric prebiotic) 20,0 Cellobiosis (dimeric prebiotic) 20,0 Oligofructose (Oligomeric Prebiotic Betafructan) 20,0 Xylan (polymer prebiotic heterosaccharide type) 20,0 Excipients: Dry berries powder (raspberries, currants, cherries) 4.0 Lemon acid 0.9 Sweetener 0.1

Many polysaccharides, which are considered to be non-utilizable in the digestive tract, can not only be disposed of, but also act as prebiotics, but not only for bifidobacteria, but for other dominant microorganisms PT. Reorientation of microorganisms and their enzymatic systems to another type of food requires a certain time (from 2 to 4 weeks). After switching to a different type of food (another prebiotic complex), a gradual reorganization of the activity of enzymatic systems occurs, which can manifest itself as an intrasymbiotic change in the qualitatively-quantitative content of microorganisms in the intestine. Accordingly, changes occur in complex cascades of biochemical reactions, biosynthesis, utilization and circulation of physiologically important substances (vitamins, interferons, steroids, etc.) at the level of symbiosis of microorganisms, followed by a response in 3-4 weeks with changes in metabolism and physiological processes at the level of a macroorganism .

For some dominant NPT microorganisms (bacteroids, clostridia, actinomycetes), the presence of enzymatic systems capable of cleaving such “unutilized” and “hard to utilize” polysaccharides as cellulose, pectins, xylans is characteristic.

Cellulose contains predominantly beta-D-glucose with a degree of polymerization of about 14 thousand. Cellobiose, a disaccharide obtained by incomplete hydrolysis of cellulose, can act as an additional eubacteriogenic factor in the prebiotic complex.

Hemicelluloses (xylans) are polysaccharides consisting of pentoses (xylose, arabinose) and hexoses (glucose, mannose, galactose), as well as uronic acids. Xylan consists of molecules connected by beta (1,4) glycosidic bonds with a degree of polymerization of 30-100. Representatives of the genus Clostidium are able to start producing the enzyme xylanase after induction with xylan. As a result, xylan is split into xylobiosis and other relatively long fragments, which, in turn, can be included in the metabolism under the influence of another symbiotic microflora.

The complex in the form of a powder can be used as a dessert prebiotic at a dosage of 5-10 g / day to improve the quality and usefulness of food digestion, as a therapeutic and prophylactic drug at a dosage of 10-25 g / day.

Product Application Results

The subjects (a group of 12 people) with a diagnosis of irritable bowel syndrome (with intestinal and extra-intestinal symptoms - high fatigue, headaches, bad taste in the mouth, insomnia, depression, etc.) used a product of 5 g 3 times a day.

The results of a microbiological study of the contents of the colon showed that while taking this prebiotic complex for 10 days, there is a statistically significant increase in not only bifidobacteria and lactobacilli, but also bacteroids, eubacteria and a decrease in the content of opportunistic microorganisms (lactose-negative and hemolysing Escherichia coli, conditionally pathogenic enterobacteria, staphylococci, Candida fungi). Within 2-3 weeks, the indicators returned to normal and the manifestations of intestinal, as well as extra-intestinal symptoms decreased - sleep was normalized, workability increased, mood stabilized, an unpleasant aftertaste in the mouth disappeared.

Example 4. Prebiotic complex for the oral cavity

Structure: Mass fraction,% Sorbitol (Monomeric Prebiotic) 10.0 Lactitol (dimeric prebiotic) 10.0 Lactosucrosis (Oligomeric Prebiotic) 10.0 Pectin (polymer prebiotic methylgalacturonate type) 15.0 Konjac gum (polymer prebiotic like galactomannan) 10.0 Potassium Lactate (non-carbohydrate prebiotic) 5,0 Excipients: Water 39.0 Lemon acid 0.9 Sweetener 0.1

Galactomannans are a group of heteropolysaccharides whose molecules consist of galactose and mannose residues. According to their intended purpose, they represent storage carbohydrates in plants; they constitute the main part of the endosperm of the seeds of some plants of the legume family and tubers.

Depending on the ratio of galactose: mannose, there are:

“Hay fenugreek gum” (~ 1: 1)

“Guar gum” (~ 1: 2); food supplement E412

"Gum packaging" (gum packaging, caesalpinia prickly ~ 1: 3); food supplement E417

“Locust bean gum” (~ 1: 4); food supplement E410

Lactitol acts as a prebiotic disaccharide.

Sorbitol is used as a prebiotic monosaccharide.

Potassium lactate is a potassium salt of lactic acid, which can act as a prebiotic for representatives of the normal flora of the oral cavity, while being a certain limiter to the development of cariogenic bacteria.

Product Application Results

The complex is made in the form of jelly (marmalade) with a packing of 10 g and is used as a product for thoroughly slow chewing, resorption in the mouth at the rate of 1 serving 2-3 times a day. The use of the product helps to restore the normal flora of the oral cavity and upper digestive tract, reduces the risk and manifestation of inflammatory phenomena in the oral cavity (gingivitis, periodontitis, caries), nasopharynx, esophagus, stomach. A group of patients was formed in the amount of 18 people with signs of gingivitis and gastritis with low acidity. After using the product after 10-14 days, 14 people noted a decrease in inflammation and bleeding of the gums, a decrease in the signs of gastritis - the feeling of fullness and heaviness in the enclosed area disappeared, the appetite returned to normal, the manifestations of nausea, unpleasant taste in the mouth and belching with air were eliminated.

Example 5. Prebiotic complex with polysaccharides of mushrooms

Sorbitol (Monomeric Prebiotic) 15.0 Isomaltulose (dimeric prebiotic) 10.0 Oligofructose (Oligomeric Prebiotic) 10.0 Arabinogalactan (polymer heteropolysaccharide) 30,0 Polysaccharides from the autumn mushroom 30,0 Excipients: Sodium benzoate 0.05 Potassium sorbate 0.05 Dry vegetable extract (in the assortment of carrots, pumpkin, beets) 4.0 Vitamin C 0.7 Sweetener (and / or spices) 0.2

As an additional polymer prebiotic, a complex of polysaccharides from autumn mushrooms (Armillariella mellea), isolated by any known technology for producing food polysaccharides, is used.

Description: homogeneous light orange powder interspersed with extracts of vegetables and spices. Method of application: for adults, 1-2 teaspoon 2-3 times a day, for children, 1 teaspoon 2 times a day with food to be included in drinks, cereals, desserts. Course duration from 10 days. Duration of use is not limited.

Product Application Results

It is shown that the use of the product increases the nonspecific resistance of the body to infectious diseases. The participants of the experiment (28 people) did not suffer from respiratory and viral diseases during the 9 months of the autumn-spring period of the year, noted good health and working capacity, a tendency to stabilize and reduce weight in people with overweight problems against a standard diet.

The composition was also used as a semi-finished product (food additive) for inclusion in the composition in the manufacture of soufflé, baked bread and marmalade in the amount of 1, 5 and 8% by weight, respectively. The resulting products met the requirements of organoleptic, physico-chemical indicators and safety indicators presented by regulatory documents.

Example 6. Prebiotic complex with filtrate culture of propionic acid bacteria

Structure: Mass fraction,% Xylitol (monomeric prebiotic) 10.0 Lactitol (dimeric prebiotic) 25.0 Inulin (polymer prebiotic fructan) 25.0 Resistant Starch (Polymer Prebiotic Polyglucan) 25.0 Apple pectin (polymer prebiotic methylgalacturonate type) 9.0 Dried Propionic Acid Bacteria Culture Filtrate 1,0 Excipients: Dry powder of berries (in the assortment of raspberries, currants, cherries, etc.) 4.0 Lemon acid 0.9 Sweetener 0.1

The vital products of propionic acid bacteria (genus Propionaceae), in particular P.freudenreichii bacteria, have a universal antimutagenic effect, because reduce the risk of mutational changes and contribute to the implementation of the repair recovery of mutated bacteria of various species and genera after exposure to various mutagenic factors of a physical, chemical, biological nature. Metabolites of propionic acid bacteria affect the rate of development, stabilize and protect the population of normal microflora and digestive tract mucosa.

The vital products of bacteria of the genus Propionibacterium, even without viable bacteria, can be considered as a non-carbohydrate prebiotic and used as part of complex prebiotic complexes to expand their spectrum of action.

Description: homogeneous light beige powder interspersed with dried berries. Packed in jars of 150 g.

How to use: for adults, 1 teaspoon 3 times a day, diluted in a glass of drink (water, juice, etc.). The duration of the course is 10-30 days.

Product Application Results

Using as a dietary food product (dietary supplement), as well as a product for inclusion in the complex of tools and methods for people with problem skin with acne (acne) showed that after 1 month more than 70% of patients against the background of generally accepted therapy and care for problematic skin, a marked improvement in skin condition was noted in comparison with the control group (improvement in 30%). A decrease in the area of acne eruptions was noted, the intensity of inflammation and the frequency of relapses decreased.

This prebiotic composition was used as a veterinary medicine to restore digestive tract microbiocenosis, normalize stool of domestic animals (cats (8 animals), dogs (10 animals)) with constipation at a dosage of 0.3-0.5 g per kg of weight. The composition in the form of a powder was mixed with wet animal feed. The use of the composition in this dosage provided after 2-7 days a pronounced effect on the regularity of stool, reduced animal anxiety due to constipation (blockages), pain during bowel movements, hemorrhoids.

The effect of the drug on non-specific resistance indices was evaluated according to the following hematological parameters: counting the number of red blood cells, white blood cells, estimation of hemoglobin level, determination of leukogram. An increase in blood leukocytes, lymphocytes, pseudozinophils, and stabilization of hemoglobin levels indicate an increase in cellular and humoral factors of animal immunity. Under the influence of the product, the process of colonization of the intestine with beneficial microflora is accelerated and the microbial landscape in the intestine changes qualitatively. The content of lactic and bifidobacteria is increasing, and the number of E. coli. decreases compared to baseline. The occurring changes in the microbiocenosis in the intestine contribute to the optimization of digestion, and therefore, normalization of stool, improvement of well-being and behavior of animals. After 3 weeks of regular intake, the condition of the coat improved - the intensity of hair loss decreased, a healthy shine was restored.

Example 7. Prebiotic complex for cosmetic, hygienic purposes.

Structure: Mass fraction,% Sorbitol (Monomeric Prebiotic) 6.0 Urea 3.0 Lactitol (dimeric prebiotic) 3.0 Potassium lactate 3.0 Zinc Lactate 0.5 Plant gum (polymer glucomannan type prebiotic) 7.0 Plantain Polysaccharides 10.0 Flax Seed Polysaccharides 20,0 D-Putnenol 1,0 Pantolactone 1,0 Tween-80 (oleic acid derivative) 3.0 Excipients: Preservative, fragrance, emulsion base up to 100.0

In addition to carbohydrate prebiotics, the following ingredients can act as prebiotic components for normoflora of the skin and mucous membranes: plant mucus, lactic acid and its salts, urea, pantothenic acid and its salts, pantolactone, biotin, oleic acid and its derivatives.

Mucus - pentosidhexoses, polysaccharides that are close in structure to fiber and pectins. A large amount of mucus is found in orchid tubers (Tubera Salep), mallow roots (Radix Althaeae), flaxseed (Semen Lini), and many other plants. The pharmacological, dermatological effect of mucus is determined by their ability to form a protective cover on the mucous tissues and thus anesthetize and protect them from the effects of irritating agents; when in contact with normoflora, they can be completely or partially utilized. Therefore, raw materials containing mucus are widely used in the treatment of inflammatory processes of the skin, hair, nails, genital mucosa.

The composition is used as a standalone tool (as a cosmetic mask) or is introduced into a cosmetic, pharmaceutical, hygiene product (in the form of a lotion, solution, suspension, gel, cream, emulsion, milk, paste, ointment, liniment, suppositories, spray, aerosol , shampoo, balm, mousse, mask), for the care of skin, mucous membranes, hair, nails, teeth and the oral cavity.

The results of applying a cosmetic mask

The prebiotic complex was applied in the form of a cosmetic mask with a layer of a thickness of 1-3 mm on previously cleansed skin of the face, neck and decollete. The exposure was 10-15 minutes. The tool was used 2 times a week. Immediately after the procedure, an increase in skin turgor was noted, a pronounced lifting effect. After 5-7 procedures, skin cleansing and lightening are noticeable.

The results of the inclusion of the composition in the composition of cosmetic cream for the care of hands and nails

A prebiotic composition of up to 5% by weight was introduced into the emulsion base using standard techniques. The cream met the requirements of regulatory documentation for cosmetic creams. The cream was applied to clean skin of the hands and nails with a thin even layer 2-3 times a day. In comparative tests of a cosmetic emulsion and cream with a prebiotic complex, a high moisturizing activity of the cream with a prebiotic complex, the ability to restore and even out skin color, as well as reduce inflammation in irritated areas of the skin of the hands, were noted. With regular use for 3 weeks of cream with the addition of a prebiotic complex, a decrease in the fragility of nails, hardening of the nail plate

The results of the inclusion of the composition in the composition of shampoos

A prebiotic complex in an amount of 2% by weight was introduced into a standard shampoo obtained by standard technology and the recipe. When washing dyed and damaged hair with dandruff (test group of 7 people), a pronounced conditioning effect of shampoo with the addition of a prebiotic complex was noted in comparison with standard shampoo. After 2 weeks of regular use, a decrease in the formation of dandruff was observed, which indicates the stabilization of the microbial landscape of the scalp and the improvement of metabolic processes.

Example 8. Prebiotic complex with autoprobiotic strains of microorganisms (autoflora synbiotic).

Structure: Mass fraction,% Mannitol (Monomeric Prebiotic) 20,0 Lactulose (dimeric prebiotic) 25.0 Oligofructose (Oligomeric Prebiotic) 25.0 Sodium Alginate (Polymer Prebiotic) 10.0 Resistant Starch (Polymer Prebiotic Polyglucan) 10.0 Apple pectin (polymer prebiotic methylgalacturonate type) 4.0 Lyophilized autoflora strain CFU / g not less than 10 ⁸ 1,0 Excipients: Lemon acid 0.9 Sweetener 0.1

Using known technologies, it is isolated from a person (animal), microorganisms of the genus Bifidobacterium are purified, grown and dried and stored (or another genus from the list of dominant genera of normoflora). If necessary (in case of illness, after intensive care, etc.), the resulting microorganism strain is cultured, dried using known techniques and incorporated into the prebiotic complex. The resulting autoflora synbiotic is used only for this person (animal), in which this strain of the microorganism is isolated. The complex can include several autoflora strains of one or more dominant genera at the same time.

The product is packaged in cans of 100 g each. A prebiotic complex in the amount of 5 g is added to the beverage and mixed before use. Application of 5 g 2-3 times a day.

The complex is recommended as a therapeutic food product for the prevention of dysbiosis or a pharmaceutical preparation for the rehabilitation of patients with courses of antibiotic therapy, chemical and radiation therapy for cancer patients with the goal of normalizing the individually specific human microflora.

Example 9. Prebiotic complex with plant extracts to improve the cardiovascular system

Structure: Mass fraction,% Xylitol (monomeric prebiotic) 10.0 Lactitol (dimeric prebiotic) 25.0 Prisoner Herb Extract (Oligomeric Prebiotic Complex) 10.0 Inulin (polymer prebiotic fructan) 25.0 Carrageenan (polymer prebiotic) 10.0 Resistant Starch (Polymer Prebiotic Polyglucan) 10.0 Apple pectin (polymer prebiotic) 4.0 Excipients: Hawthorn fruit extract 4.0 Buckwheat herb extract 1,0 Lemon acid 0.9 Sweetener 0.1

The aqueous extract of the European inland grass contains a complex of oligosaccharides, organic acids, glycosides, phenolcarboxylic acid derivatives. After drying, the extract is a concentrate of prebiotic carbohydrates with an additional set of substances that favorably affect the activity of the coronary vessels, blood pressure, and thyroid gland.

The complex of oligosaccharides from the herd of grass (Herba Lycopi) consists of a mixture of raffinose (trisaccharide), stachyose (tetrasaccharide), verbascose (pentasaccharide).

Appointment: a prebiotic complex with plant extracts to improve digestion, reduce high cholesterol, improve blood vessels, blood pressure and cardiac activity.

The product was used in powder form. Directions for use: 1 teaspoon (5 g) 3 times a day with water.

The prebiotic complex with plant extracts was used to improve digestion, reduce high cholesterol, improve blood vessels, blood pressure and cardiac activity. Used as a prophylactic for inclusion in the complex of generally accepted means and procedures for people with a high risk of cardiovascular disease.

18 people with metabolic syndrome (overweight, arterial hypertension, impaired lipid and carbohydrate metabolism) received a prebiotic complex of 5 g 3 times a day during basic therapy. After 14 days, it was noted that the complex stabilized and increased the effectiveness of basic therapy; in comparison with the control group, the recovery of carbohydrate and lipid metabolism was accelerated. After 2 months, a decrease in body mass index was observed in all patients, which was not observed in the control group.

Example 10. Prebiotic complex with pollen polysaccharide

Structure: Mass fraction,% Sorbitol (monomeric prebiotic) 20,0 Lactitol (dimeric prebiotic) 20,0 Oligofructose (Oligomeric Prebiotic) 20,0 Complex BAS pollen 5,0 Complex BAS fenugreek 4.0 Guar gum (polymer prebiotic like galactomannan) 10.0 Resistant Starch (Polymer Prebiotic Polyglucan) 10.0 Apple pectin (polymer prebiotic methylgalacturonate type) 10.0 Lemon acid 0.9 Sweetener 0.1

Plant pollen contains polysaccharide callose, which has prebiotic properties. Lipids and other non-polysaccharide substances were removed from plant pollen by successive extraction. After that, the pollen was dried and crushed.

The resulting complex, consisting mainly of callose and water-soluble biologically active substances (including secalosides and cyclic hydroxamic acids), was introduced into the prebiotic complex.

In a similar manner, a BAS complex was prepared from hay fenugreek seeds. Hay fenugreek extract contains gum (a type of glucomannan) as a prebiotic component and trigonellin as a problem-oriented biologically active substance.

Purpose: prebiotic complex with pollen and fenugreek extracts for inclusion in the diet of middle-aged and elderly people, to improve metabolism, reduce high cholesterol, and reduce the risk of complications from the organs of the reproductive system.

The composition is used as in examples 1-3.

Example 11. Prebiotic complex with micro and macro elements (with salts of zinc, magnesium and calcium)

Structure: Mass fraction,% Xylitol (monomeric prebiotic) 20,0 Lactitol (dimeric prebiotic) 20,0 Oligofructose (oligomeric prebiotic fructan) 20,0 Resistant Starch (Polymer Prebiotic Polyglucan) 20,0 Guar gum (polymer prebiotic like galactomannan) 7.0 Excipients: Zinc Lactate 0.3 Iron (II) Lactate 0.4 Calcium lactate 9.2 Magnesium Lactate 3.0 Sweetener 0.1

Appointment: a prebiotic complex with organic salts of zinc, iron, magnesium and calcium. Helps to improve the absorption of food components and compensate for nutritional deficiencies in these micro and macro elements, including with various forms of anemia.

The composition is used as in examples 1-3.

Example 12. Prebiotic complex for sports nutrition

Structure: Mass fraction,% Palatinosis (isomaltulose) 57.5 Resistant starch 20,0 Oligofructose 7.0 Inulin 3,5 Lactitol (lactitol) 2,8 Ground Flax Seeds 2.6 Shredded sesame seeds 2.6 Guar gum 1,5 Apple Pectin 1,2 Citric Acid Monohydrate 1,2 Stevia Extract (Sweetener) 0.1

According to modern ideas about the processes of ensuring the energy needs of the body, it is known that human microbiocenosis contributes a large share to the total energy of the body due to the release of energy substances and the performance of those works and functions that our body cannot perform. The energy contribution of the work of microbiocenosis is comparable with the level of energy (calorific value) of food and is about 2 thousand kcal.

Examples of the work of microbiocenosis in providing our body with energy:

- the final, complete, deep and effective digestion of food in the large intestine - the effective development of the entire energy potential of food (“pre-digestion”), because our digestive system only partially assimilates food and is mainly components that are readily available for digestion and assimilation;

- digestion, disposal of body cells and bacteria that have served their term (for example, mucous cells);

- the allocation of short-chain (volatile) organic acids, alcohols and gases, which supply energy to the cells of the mucous membrane of the digestive tract and other organs;

- the formation of vitamins and other important substances;

- reduction of the body’s energy consumption for inactivation and removal of end products of metabolism (under stress or disease) and harmful (toxic) substances, pathogenic bacteria, etc. This allows you to reduce the load on the liver and other organs and systems involved in cleansing and detoxification;

- warming and maintaining the desired temperature in the internal organs (intestines, liver, pancreas, spleen, etc.) to perform their functions in the optimal temperature regime.

With dysbiosis (according to experts, dysbacteriosis in 50-90% of the population), the normal microflora ceases to partially or fully fulfill these functions. Thus, the energy efficiency of the body with dysbiosis may decrease by more than 15%.

With dysbiosis (or constant risk of getting it in modern living conditions), regular intake of balanced complexes of prebiotic substances (in the amount of 5-15 g per day) can increase the energy efficiency of the body (or reduce the risk of its fall) and ensure the stability of a high level of energy for that fraction , which is created and invested by microbiocenosis in the general piggy bank of the body’s energy, i.e. by 15-25%.

This complex is used for the preparation of sports nutrition products and inclusion in the diet of people with high physical and energy stresses (athletes, fitness workers, athletes, tourists, etc.). Regular use of the product in a regimen of 3 times a day for 5 g for 3 weeks for people (a group of 12 people aged 18 to 40 years old) involved in cycling and hiking showed that overall well-being increased, performance increased, and work decreased fatigue, the threshold of fatigue was pushed back, the concentration of attention increased, the number of errors decreased.

Claims (16)

1. Composition for normalizing the microflora of the body, containing at least 3 prebiotic substances taken from four groups of prebiotics with different lengths of the molecular chain:
- monomeric prebiotics (number of units 1);
- dimeric prebiotics (number of links 2);
- oligomeric prebiotics with a number of units from 3 to 10;
- polymer prebiotics with more than 10 units;
with the following content of components, wt.%:
prebiotic substances in total not less than 50.0 Excipients up to 100 2. The composition according to claim 1, characterized in that it contains, wt.%:
monomeric prebiotic 0.5-50.0 dimeric prebiotic 0.5-50.0 oligomeric prebiotic 0.5-50.0 Excipients up to 100 3. The composition according to claim 2, characterized in that it further comprises 0.5-50.0 wt.% Polymer prebiotic. 4. The composition according to claim 1, characterized in that it contains, wt.%:
dimeric prebiotic 0.5-50.0 oligomeric prebiotic 0.5-50.0 polymer prebiotic 0.5-50.0 Excipients up to 100 5. The composition according to claim 1, characterized in that it contains, wt.%:
monomeric prebiotic 0.5-50.0 oligomeric prebiotic 0.5-50.0 polymer prebiotic 0.5-50.0 Excipients up to 100 6. The composition according to claim 1, characterized in that it contains, wt.%:
monomeric prebiotic 0.5-50.0 dimeric prebiotic 0.5-50.0 polymer prebiotic 0.5-50.0 Excipients up to 100 7. The composition according to any one of claims 1 to 3, 5, 6, characterized in that it contains any substance or combination of substances selected from the group - xylitol, sorbitol, maltitol, D-panthenol (dexapanthenol), organic acids as a monomer prebiotic mainly lemon. 8. The composition according to any one of claims 1 to 4, 6, characterized in that it contains any substance or combination of substances selected from the group of lactulose, lactitol, cellobiosis, melibiosis, isomaltulose as a dimeric prebiotic. 9. The composition according to any one of claims 1 to 5, characterized in that it contains any substance or combination of substances selected from the group of lactosucrosis, raffinose, cellotriose, stachyose, verbiosis, fructooligosaccharide, galactooligosaccharide, transgalactoligosaccharide, gluco-oligolaccharide, as an oligomeric prebiotic. , xylo-oligosaccharide, isomaltooligosaccharide, gentio-oligosaccharide. 10. The composition according to any one of claims 1, 3-6, characterized in that it contains as a polymer prebiotic any substance or combination of substances selected from the group - inulin, arabinogalactan, betaglucan, pectin, resistant starch, vegetable gum, lignin, alginate , agar-agar, agarose, pullulan, kurdlan, glycosaminoglycan, hyaluronic acid, glycosaminoproteoglycan, chitosan, cyclodextrin, carrageenan, glucomannan, levan, callose, cellulose, a complex of polysaccharides from fruit bodies of edible macromycetes. 11. The composition according to any one of claims 1, 3-6, characterized in that it contains at least one heteropolysaccharide selected from the group: gum, carrageenan, hemicellulose, galactomannan, arabinogalactan, glucuronoarabanogalactan, glucomannan as a polymer prebiotic. 12. The composition according to any one of claims 1 to 6, characterized in that it contains any substance or a combination of substances selected from the group as excipients — water, alcohols, acidity regulators, taste regulators, consistency regulators, gelling agents, surfactants , flavors, perfumes, colorants, disintegrants, plant extracts, crushed plant parts, spices, sweeteners, solvents, preservatives, provitamins, vitamins, macro and micronutrient salts, biologically active substances and their compositions, gender chennye from mineral, vegetable, animal, fungal, algal, bee products or microbiological sources. 13. The composition according to claim 1, characterized in that it further comprises substances with a prebiotic effect in relation to the normal microflora of the skin and mucous membranes selected from the group urea, pantolactone, biotin, pantothenic acid, oleic acid, salts or esters of these acids. 14. The composition according to p. 13, characterized in that it is a part of cosmetic, pharmaceutical, hygiene products for skin, mucous membranes, hair, nails, teeth and oral cavity at a concentration of not less than 0.5 wt.%. 15. The composition according to claim 1, characterized in that it is used as a functional food product, diet product, dessert, goodies, baby food, preventive, rehabilitation, pharmaceuticals, sports nutrition, premix, dietary supplement for human food or animal feed . 16. The composition according to claim 1, characterized in that it contains as an additional prebiotic component with an antimutagenic effect the vital products of a culture of bacteria of the genus Propionibacterium.