RU2756855C1 - Biologically active food supplement of encapsulated form - Google Patents

Abstract

FIELD: medicine, pharmaceutics, food industry.

SUBSTANCE: invention relates to medicine, pharmaceuticals, herbal medicine and the food industry. A biologically active additive (dietary supplement) of a encapsulated form containing a complex of biologically active substances (BAS) in the form of a dry extract as an active component, which includes the roots of devil’s club, horsetail grass, dogwood fruits, fruits of bur beggar-ticks, roots and rhizomes of elecampane, blueberry shoots, goat’s-rue grass, mulberry leaves and strawberry leaves in the ratio 1.5:1.5:1:1:1:1:1:1:1, and a complex of auxiliary substances, including a filler, binder, disintegrant, anti-sticking, sliding. The method for obtaining dietary supplements of the encapsulated form includes obtaining a liquid extract followed by evaporation, purification of the extract followed by obtaining a dry extract, mixing with auxiliary substances and encapsulation. Dietary supplements are used as a source of flavonoids and tannins.

EFFECT: invention makes it possible to obtain dietary supplements in an encapsulated form, which satisfies the human body’s need for the necessary amount of flavonoids and tannins without pronounced allergic and undesirable reactions, and also has a cleansing, antioxidant, regenerating, decongestant, cardioprotective, vasodilating, venotonic, anti-carcinogenic, anti-inflammatory effect.

9 cl, 11 tbl, 5 ex

Description

The group of inventions relates to medicine, pharmaceuticals, herbal medicine and food industry. Mainly the invention relates to a complex of biologically active substances (BAS) containing a dry extract of the following composition: roots of zamanikha, horsetail herb, cornelian fruits, fruits of a tripartite train, roots and rhizomes of elecampane, blueberry shoots, galega grass, mulberry leaves, strawberry leaves with the following ratio of parts 1.5: 1.5: 1: 1: 1: 1: 1: 1: 1. Also described is the finished form of a biologically active additive (BAA), which is an encapsulated form, which includes the above-mentioned complex of biologically active substances and a complex of excipients. In addition, the technology of obtaining a complex of biologically active substances and a finished form of biologically active additives is described. Additionally, the proposed dosage regimen of dietary supplements in encapsulated form, taking into account the needs of the human body in flavonoids and tannins. The group of inventions makes it possible to obtain a dietary supplement in encapsulated form, which, with the claimed production method, the quantitative and qualitative ratio of the ingredients of the composition, provides the human body's need for the required amount of flavonoids and tannins without pronounced allergic and undesirable reactions, and which has a cleansing, antioxidant, regenerating, decongestant, cardioprotective, vasodilating, venotonic, anticarcinogenic, anti-inflammatory action. In particular, the claimed composition of dietary supplements in encapsulated form will have a significant positive effect on the gastrointestinal tract, kidneys, liver, and, in particular, on the pancreas.

Currently, there is a fairly wide need for nutrient support for the body as a whole, and for certain organs and systems of a person, from outside. Against this background, in recent decades, the close attention of researchers has been attracted by such products that are capable of having a preventive and therapeutic effect on the human body, and at the same time minimizing allergic and unwanted reactions. These, for example, include the product of secondary plant metabolism - flavonoids, due to a wide spectrum of action.

Flavonoids are plant phenolic compounds, the structural basis of which is made up of 2 benzyl rings (A and B) connected to each other by a heterocyclic pyran or pyrone (ring C). Experimental and clinical studies have revealed their antioxidant, cytoprotective, hepatoprotective, antihypoxic and many other effects. No less interest is directed to the study of tannins (DW). DV or tannins represent compounds of the polyphenolic structure, subdivided into hydrolysable and condensed. The condensed ones are characterized by gastroprotective, antioxidant, antimutagenic, antitumor, antibacterial, antiviral activity. Hydrolyzed tannins have anti-candidiasis, antifibrotic effects, inhibit the HIV-induced cytopathic effect. DVs are active against methicillin-resistant Staphylococcus aureus and Epstein-Barr virus.

Flavonoids, tannins and their analogs are essential for humans, i.e. requiring constant intake with food or in the form of drugs and food additives.

Uncontrolled or excessive consumption of foods or food additives that are sources of DV and / or flavonoids may cause undesirable effects, such as allergic reactions, slowing down of intestinal motility, constipation, and impaired absorption of vitamins. In case of violation of the dosage regimen, in most cases, prophylactic and therapeutic effects are not achieved.

Low level of medical compliance is becoming quite common when performing wellness and preventive procedures. First of all, this is facilitated by the shape and delivery of the source of nutrients and health-improving substances. These forms include tinctures, balms, teas, when it comes to nutritional supplements or diets containing a specific list of foods saturated with essential nutrients and / or health-promoting substances.

Some of the ready-made forms, for example, tinctures, are often addictive, especially sedatives - a person without a sedative begins to feel increased anxiety. In addition, tinctures and balms contain alcohol, which means that they are contraindicated for children, pregnant women, breastfeeding and alcoholism. They are also contraindicated for people in those professions where a high concentration of attention is required and when using certain medications. We must not forget about allergic reactions.

The effectiveness of using compositions from collections of dry herbs is not always maximum due to incomplete extraction of extractive substances or the loss of activity of these substances when making teas at home. In addition, such compositions are poorly protected from environmental influences during storage, transportation, and operation. Compositions requiring brewing are often used with a violation of the intake or dosing regimen: they are over-brewed, inappropriate containers and preparation modes are used, etc.

Thus, the objective of the invention is to develop a finished form of dietary supplements, which is a source of flavonoids and DV with such a quantitative and qualitative composition that would have the most beneficial effect on these organs and systems of vital activity, in particular, showed high efficiency in relation to the gastrointestinal tract, liver, kidneys and pancreas. glands, and at the same time practically would not have allergic and unwanted reactions. In addition, another object of the invention is the development of such a finished form that would contribute to an increase in medical compliance when performing health-improving and prophylactic procedures. An additional object of the invention is a method for obtaining a finished form, which would involve the optimal qualitative and quantitative ratio of the ingredients of biologically active substances and excipients.

The task is solved by creating a dietary supplement in a capsulated form, containing a complex of biologically active substances (BAS) in the form of a dry extract as an active component, including the roots of the lard, horsetail grass, dogwood fruits, fruits of the tripartite train, roots and rhizomes of elecampane, shoots blueberries, galegi grass, mulberry leaves and strawberry leaves in a ratio of 1.5: 1.5: 1: 1: 1: 1: 1: 1: 1 and where the sum of flavonoids in terms of rutin is 1.75 - 2.03 mg, and the sum of tannins in terms of tannin 11.13 - 13.4 - mg per capsule, and a complex of excipients, including a filler, binder, disintegrant, anti-stick, sliding. Additionally, the problem is solved by obtaining a dietary supplement of encapsulated form, where, in a preferred embodiment of the invention, microcrystalline cellulose 101 (MCC 101) acts as a filler, α-polyvinylpyrrolidone (α-PVP K25) acts as a binder and disintegrant, and silicon dioxide acts as a sliding agent. colloidal (aerosil) and / or magnesium stearate, and colloidal silicon dioxide (aerosil) is chosen as anti-sticking agent. Additionally, the task is solved by the optimal selection of the dose, which contributes to the achievement of the best effect with almost complete absence of allergic and undesirable phenomena and is, with the declared qualitative and quantitative composition of the BAS complex in the form of a dry extract, 2 capsules 2 times a day. In addition, the task is solved by the fact that experimentally developed a method for obtaining an encapsulated form that solves the tasks.

The technical result of the claimed group of inventions is to obtain a dietary supplement, which, with the claimed method of production, the quantitative and qualitative ratio of the ingredients of the composition, provides the body with the necessary amount of tannins and flavonoids for prophylactic and therapeutic effects on the organs and systems of human vital activity, in particular in relation to the gastrointestinal tract, kidneys, liver and the pancreas. The claimed composition and method make it possible to obtain such a dietary supplement composition, which has a pronounced synergistic effect, and the claimed form and dosage regimen make it possible to achieve the convenience of taking the food supplement and maintain a high level of medical compliance. Due to the selected composition of biologically active substances in the form of a dry extract, which acts as an active component, a complex of excipients and the finished form of the dietary supplement, it has improved stability, bioavailability and prolonged action.

There is a composition (RU2458701, 01/31/2011), which includes dry extracts of galega officinalis, garcinia cambogia plants, flax seeds, bean peel, sylvester gimnema, marsh grass, wheatgrass rhizomes, as well as magnesium oxide and vanadium sulfate as trace elements.

The composition is aimed at a narrow range of applications - the prevention and treatment of insulin-dependent diabetes mellitus. Nevertheless, the composition does not replace traditional therapy for this type of diabetes - insulin therapy and a strict diet.

There is another composition with an antidiabetic effect (RU 2430735, 12/30/2009), which includes: the herb of the goat's rue (galegi) and the leaf of the common bean fruit, characterized in that it additionally contains walnut leaves, white mulberry leaves, and mountaineer grass bird (knotweed), agaric, lingonberry leaves, small periwinkle, roots of medicinal dandelion and elecampane high, flowers of the heart-shaped linden and the inflorescence of the scepter mullein.

Another composition known from the prior art, having an antidiabetic effect (RU 2611353, 02.21.2017) is represented by the following composition: herb of medicinal goat's rue (galegi), medicinal dandelion roots, heart-shaped linden flowers, white mulberry leaves, high elecampane roots, common lingonberry leaves , leafs of common beans, laurel leaves, a series of wilted grass.

All of them have a narrowly targeted spectrum of action, contain pronounced allergens or elements that can contribute to the manifestation of undesirable reactions. For example, walnut leaves are contraindicated in certain pathologies, such as high blood clotting, acute intestinal diseases, pancreatitis, neurodermatitis, thrombophlebitis. In addition, an irregular intake of such substances, especially in decoctions, can lead to severe allergic reactions and even spasms in the vessels of the brain. Another example is the heart-shaped linden flower, which is quite often used in decoctions and infusions. Excessive use and difficulty in controlling the dosage can lead to severe allergic reactions, in addition, with the daily use of infusions and decoctions containing linden flowers, there is an additional load on the heart.

The composition described in patent RU 2611353 was selected as the closest analogue.

Thus, there is a need to create such a dietary supplement that will have a wide practical and therapeutic profile, in particular cases, have a beneficial effect on the gastrointestinal tract, liver, kidneys and pancreas, will be the optimal source of flavonoids and DV, and when taken does not show pronounced allergic and unwanted reactions.

According to the task at hand, the applicant has proposed a dietary supplement of encapsulated form. When developing the composition of dietary supplements with high quality indicators with a therapeutic effect, the same technological approaches and requirements were used as in the development of drugs.

When developing, the applicant focused on the optimal amounts of flavonoids and tannins for prevention and recovery, which a person can receive when taking dietary supplements, so that at the same time the maximum positive effect is achieved without the manifestation of undesirable reactions.

It was found that the optimal amount of flavonoids in terms of rutin and tannins in terms of tannin for the selected form should be present in amounts of 3.5-4.26 mg and 22.26-26.8 mg, respectively. Such a volume would correspond to 1 filter bag weighing 1.5 g. As a result of the development of encapsulated dietary supplements, it was found that the BAS in 1 filter bag weighing 1.5 g corresponds to the amount of BAS in 2 capsules, thus, with the recommended intake of 2 filter package per day, the optimal mode of taking capsules is 2 capsules 2 times a day. Moreover, for each capsule there are 1.75-2.13 mg of flavonoids in terms of rutin and 11.13-13.4 mg of tannins in terms of tannin.

To achieve a synergistic effect and to maximize the elimination of undesirable reactions or to bring the latter to the status of the lowest possible, a qualitative and quantitative composition was experimentally selected, including the roots of the high lure, horsetail grass, dogwood fruits, fruits of the tripartite series, roots and rhizomes of elecampane, shoots of common blueberries , galegi grass, mulberry leaves and strawberry leaves in a ratio of 1.5: 1.5: 1: 1: 1: 1: 1: 1: 1.

All structural and physicochemical characteristics of biologically active substances and excipients were studied, the information obtained was used to develop the composition and technology for producing biologically active additives.

The root and rhizome of elecampane contain inulin (up to 44%) and other polysaccharides, alantolactone, essential oil (up to 4.5%), saponins, bitter substances, alkaloids (a small amount), mucus, gum, pectins, vitamin E, ascorbic acid.

The plant material has anti-inflammatory effect, improves appetite, regulates intestinal motility, reduces its secretory activity, stimulates the process of bile formation, gallbladder secretion.

Modern medicine recommends dogwood fruits as a vitamin supplement for dietary nutrition, both dried and fresh.

Dogwood fruits are drupes, rich in the following vitamins and minerals: organic acids - 100%, vitamin C - 50%, potassium - 14.5%, iron - 22.8%. The fruits contain tannins, with a characteristic choleretic, anti-inflammatory and diuretic effect; flavonoids responsible for strengthening the vascular wall.

Strawberry leaves contain tannins, ascorbic acid, flavonoids, traces of alkaloids. Extracts obtained from strawberry leaves have tonic and choleretic properties.

Horsetail herb is rich in mineral salts, especially silicic acid in the form of soluble compounds. Also contains flavonoids, tannins, oxalic and malic acids, traces of alkaloids, resinous and bitter substances, carotene, ascorbic acid.

Extracts obtained from raw horsetail have hemostatic, anti-inflammatory and especially diuretic properties.

The herb galegi (goat's rue) contains carbohydrates, saponins, the alkaloid galegin, vazicinone, peganin, glycoside galluteolin, tannins, tannin, phenol carboxylic acids, carotene, ascorbic acid, bitterness. Goat's rue has diuretic and choleretic properties.

White mulberry leaves contain aldehydes, flavonoids (rutin, quercitrin, isoquercitrin, quercetin, kaempferol), tannins, sterols (β-sitosterol, capesterol), organic acids (malic, citric, succinic, tartaric), coumarins, resins, essential oils carotene, vitamin C. The extract from the leaves is used in medicine as an anti-inflammatory, analgesic, hypoglycemic agent.

The rhizomes of high zamaniha contain essential oil, alkaloid aralin, triterpene glycosides, phenolic compounds, and minerals. The extracts obtained from the raw material are high, have a diuretic and choleretic effect, increase the secretion of the pancreas.

Blueberry leaves contain tannins, flavonoids (astralgin, rutin, kaempferol, quercetin, isoquercetin, meratin), oleanolic acid, carotenoids, phenol and its derivatives, murtine alkaloid, essential oil, anthocyanins, catechins, ascorbic acid, organic acids.

Blueberries contain carbohydrates (glucose, sucrose, fructose), organic acids (citric, malic, lactic, succinic, oxalic), vitamins C, PP, B2, B3, carotene, essential oil, flavonoids, tannins.

Blueberry extracts have astringent, anti-inflammatory, hypoglycemic, analgesic properties.

The herb of the tripartite series contains flavonoids, tannins and bitterness, essential oil, carotene, coumarins, red flobafen, ascorbic acid, trace elements.

Herbal extracts have diaphoretic, diuretic and choleretic properties.

Due to the selected complex of biologically active substances, the plant material unexpectedly acquires a pronounced anti-inflammatory and choleretic effect, and is also a valuable source of vitamins.

The experimentally selected composition in specified proportions showed that the complex of biologically active substances is of high practical value for the gastrointestinal tract, kidneys, liver, and especially for the pancreas.

When selecting the optimal composition for the encapsulated form of dietary supplements, which is a full-fledged source of flavonoids and tannins, it was unexpectedly found that all of the above ingredients in the specified quantitative ratio have a synergistic effect.

The specified qualitative and quantitative composition can be considered ready for use if a dry extract is prepared from it for transferring the extract into any of the finished forms known from the prior art. The preferred ready-made form for the claimed composition of the dry extract is considered to be herbal collection in bulk, herbal collection in a filter bag, tincture, balsam, granular, tableted, capsule forms. The most preferred is the capsule form established for the specified composition experimentally.

The indicators of the quality of plant raw materials were evaluated and calculated for compliance with the indicators necessary for solving the task, which are reflected in table No. 1.

Table 1 - Indicators of the quality of plant raw materials Quality indicators Requirements Test results External signs A mixture of inhomogeneous particles of plant materials of brownish-green color with brown, grayish-white blotches Compliant The taste of water infusion Spicy, slightly astringent Compliant The smell of water infusion Weak, typical of steamed plants Compliant The presence of impurities Not allowed Not found Mass fraction of moisture,% no more 13.00 8.50 Mass fraction of extractive substances extracted by water,% not less 32.50 34,00 Tannins in terms of tannin,%, not less 4,00 4.60 Flavonoids in terms of rutin,%, not less 0.80 0.95 Particles that do not pass through a sieve with holes of 3 mm,%, no more 10,00 4.60 Particles passing through a sieve with holes of 0.2 mm,%, no more 15.00 5.2 Microbiological purity According to the requirements Compliant Package content weight, kg 15.00 ± 5% 15.05

Currently, the most common dosage form for dietary supplements is the tablet form. The technology of tableted dietary supplements is widely used by manufacturers. However, one should take into account its features, which the applicant attributes to the disadvantages: multistage, a large amount of technological auxiliary substances in formulations, the impact on biologically active substances of stressful technological conditions, such as humidification, high temperatures, pressing, which can lead to their destruction, which will negatively affect stability and effectiveness of biologically active substances.

In accordance with the task, the applicant has established that it is the capsules that make it possible to ensure high dosing accuracy; during the production of the capsules themselves, the BAS is not exposed to aggressive technological influences, which has a positive effect on the stability and effectiveness of the BAS and allows maintaining the synergistic effect. Additionally, it is worth noting the attractive appearance, masking the unpleasant taste and smell of biologically active substances.

The biopharmaceutical capabilities of modifying the release of biologically active substances from capsules make it possible to vary it in a wide range - from fast to phase and prolonged.

For the claimed capsule form, all types of capsules known from the prior art are valid. Nevertheless, it will be impossible to determine the most preferable for an average specialist without preliminary approbation. The preferred variant of the capsule form in the present invention are capsules made of gelatin, a natural product of hydrolysis of collagen containing raw materials that are waste from food industry.

Gelatin is a polypeptide whose molecule consists of amino acids, including: glycine (about 30%), proline, hydroxyproline, alanine, glutamic and aspartic acids. The amino acids of gelatin have an effect on the body: they improve metabolism, increase mental performance and strengthen the heart muscle, have a beneficial effect on the tissues of the musculoskeletal system, the mucous membrane of the gastrointestinal tract during erosions and peptic ulcer disease and are one of the main sources of energy for the central nervous system, muscles and the brain. The selected type of capsule is easily absorbed and does not give side reactions, in addition, the selected composition of the capsule enhances the synergistic effect of the BAS complex in the form of a dry extract.

Additionally, it should be noted that gelatin, being a natural product, is easily absorbed by the body, quickly dissolves in the acidic environment of the stomach (which is facilitated by the presence of gastric protease pepsin) and releases the contents of the capsules, thereby facilitating the rapid entry of biologically active substances in the form of a dry extract into the body.

Hypromellose capsules are produced by synthetic modification of cellulose and are considered safe for human consumption. It is practically insoluble in hot water, in acetone, in anhydrous ethyl alcohol and in chloroform, but it dissolves in cold water to form a colloidal solution, and exhibits reversible temperature gelation.

Modification of the HPMC molecule with methoxy and hydroxy propoxy groups makes it possible to obtain products with variations in many properties, for example, gelation temperature, viscosity, elasticity, and hydration.

This makes it possible to create products with modified release and with increased resistance to storage conditions and mechanical processing.

HPMC is well compatible with known excipients and has gelatin-like properties. HPMC meets the dietary and cultural needs of all patients. Meets production demands - capsules can be produced and filled with existing equipment. It is characterized by proven safety information and is approved for pharmaceutical use. In addition, it improves the characteristics of capsules, their strength, protection against moisture from microbial contamination, and high compatibility with products.

Hypromellose capsules are more moisture stable than gelatin capsules. The moisture content of the capsules themselves is 6-7%, which is lower than the moisture content of gelatin capsules, which is 12-13%. This is extremely important for hygroscopic biologically active substances and for conditions of filling, transportation, storage as empty capsules.

However, there is a delay in disintegration time of the hypromellose capsule of about 5 minutes in simulated gastric environment and 10 minutes in simulated intestinal fluid. As a result, gelatin capsules remain the leading choice in the choice of encapsulated form for unlimited and unmodified release of biologically active substances.

Due to the absence of the need to modify the release of dietary supplements, capsules from gelatin were chosen for further pharmaceutical development, due to the physicochemical properties, as well as the expected parameters of the release, dissolution and absorption of the biologically active substances. Nevertheless, based on your described types and properties of capsules, various options for the composition of biologically active substances in the form of a dry extract are valid, including options for modified and / or prolonged action, which can be reproduced by methods known from the prior art for a specialist of average level.

The applicant considered all types of extracts, however, for the task at hand, a dry extract from plant raw materials is the most preferable.

Dry extracts are concentrated extracts from plant raw materials, which are free-flowing masses with a moisture content of no more than 5%. Dry extracts are obtained by drying thick extracts or directly from a purified extract by methods that ensure maximum preservation of biologically active substances: by convection or freeze drying.

The most preferred form of the active substance, placed in hard capsules, is a substance made in the form of granules or powder. In the case of a low dosage of the active substance, fillers (diluents): mannitol, lactose, microcrystalline cellulose, corn starch and other traditional explosives approved for pharmaceutical use are introduced into the formulations to ensure the accuracy of dosing by the capsule filling machine.

The choice of excipients is closely related to the technology of preparing the encapsulated mixture for filling; accordingly, the technological properties of the BAS were studied to select and substantiate the preparation technology.

Example 1. Determination of the flowability of biologically active substances for the subsequent production of the encapsulated form.

The powdery content must first of all have good flowability. Looseness, in turn, depends on many characteristics of the powder: on the fractional composition, amorphousness and moisture content of the substance. Since flowability is a complex characteristic, it is customary to determine it in two ways: by the flow rate from a standard funnel and by the value of the angle of repose. Angle of repose - the angle between the generatrix of the bulk material cone and the horizontal plane. The slope angle characterizes the effect of friction between particles and the effect of gravity on the powder mass, assesses the effect of particle size, shape and electrostatic interaction between particles during the pouring of powder from the hopper of a capsule filling machine. The value of the angle of repose depends on the shape, size and cohesive properties of the particles; it varies over a wide range: from 25 ° to 30 ° for well-flowing materials, from 60 ° to 70 ° for poorly free-flowing materials.

Like other characteristics of bulk masses, the bulk density is a complex indicator that depends on many others: particle size distribution, moisture content, packing density in the layer. It is important that this is not a constant value, it can change under the influence of vibration and even during storage in a warehouse. Therefore, a distinction is made between the minimum bulk density of a loosely poured powder and the maximum — the bulk density after compaction — for a powder loosely poured, but compacted by shaking. Bulk density is closely related to the volume of the capsule, the number of which is selected depending on the mass of the contents of the capsule.

The methods are presented in the State Pharmacopoeia of the Russian Federation (GF RF). The qualitative assessment of the flowability of the powder is determined by the values of the Carr and Hausner indices, which are calculated on the scale given in USP 31 (table 2).

Table 2 - Estimation of the Hausner and Carr indices Carr index Compressibility assessment Hausner index ten very good 1.00-1.11 11-15 good 1.12-1.18 16-20 average 1.19-1.25 21-25 satisfactory 1.26-1.34 26-31 bad 1.35-1.45 32-37 very bad 1.46-1.59 Over 38 very, very bad More than 1.60

Determination of the fractional composition was carried out in accordance with OFS.1.1.0015.15 "Sieve analysis" on any suitable electromagnetic sieve analyzer. An accurate sample of the material was divided into fractions by sieving through a set of sequentially assembled sieves with aperture sizes of 2 mm, 1.25 mm, 710 μm and 315 μm.

The weighed portion was placed on the top largest sieve and the entire set was shaken by hand for 5 minutes. Then the sieves were removed one by one, the material remaining on each sieve was weighed separately. Then the percentage of each fraction of the total weight of the sample was found. Sifting is complete if, with additional shaking, the amount of material passing through the sieve for 1 minute is less than 1% by weight of the material remaining on the sieve.

The determination of the bulk density was carried out in accordance with the General Pharmacopoeia Monograph.1.4.2.0016.15 "Degree of flowability of powders" on any suitable tester for determining the bulk density. During the analysis, a sample of the material was weighed with an accuracy of 0.001 g and poured into a glass measuring cylinder with a capacity of 50 ml. The vibration amplitude of 3 mm and the frequency of 150 vibrations per minute were set. After 5 minutes, the device was turned off.

Bulk density was calculated by the formula: ρ = m / v

where ρ is the bulk density before or after tapping (compaction), g / cm ³ ;

m is the mass of the material, g;

v is the volume of powder in the cylinder before or after shaking (compaction), cm ³ .

Determination of the angle of repose was carried out in accordance with OFS.1.4.2.0016.15 "Degree of flowability of powders" on any suitable flow tester. An exact weighed portion of the powder, about 100 g, was poured into the funnel of the device, the nozzle diameter was 10 mm. The angle of repose is set in the device using a laser sensor.

Hausner and Carr indices

Based on the values of the bulk density, the Hausner index and the Carr index are calculated, according to the values of which the flowability and compressibility are estimated.

Index calculation formulas:

Hausner index (H) H = P _y / ρ;

Carr index (J) J = 100⋅ (P _y - ρ) / P _y ;

where P _y - bulk density after compaction;

ρ is the bulk density.

The results obtained after measuring 6 samples are shown in Table 3.

Table 3 Indicator, units rev. The quantity 1 2 3 4 5 6 The average Particle size ≥100 μm ≥100 μm ≥100 μm ≥100 μm ≥100 μm ≥100 μm ≥100 μm Bulk density before compaction, g / ml 0.37 0.38 0.39 0.38 0.38 0.37 0.37 ± 0.03 Bulk density after compaction, g / ml 0.57 0.58 0.57 0.58 0.57 0.57 0.57 ± 0.02 Angle of repose, degrees 31 thirty 29 thirty thirty 32 30 ± 3 Humidity, % 0.20 0.22 0.25 0.25 0.21 0.19 0.23 ± 0.3 Carr index 11.80 12.20 12.50 13.90 12.10 12.50 12.50 ± 1.3 Hausner index 1.12 1.14 1.15 1.15 1.14 1.12 1.15 ± 0.2

The angle of repose corresponds to 30-32 degrees, the powder was not dusty and spilled out freely from the funnel. The bulk density before compaction is 0.37, and after compaction - 0.57, which confirms the use of the extract in the form of an encapsulated form. On the basis of the calculated values of the Carr and Hausner indices, the flowability of the extract was assessed as "good".

It was unexpectedly found that when adding excipients, taking into account the dosage of biologically active substances, in addition to improving the technological characteristics, the bioavailability of the active ingredient itself increased.

Example 2. Development of the composition of the encapsulated form of a biologically active additive.

Experimentally, the optimal composition of dietary supplements of a capsulated form was selected, containing as a BAS in the form of a dry extract, the previously indicated composition, including the roots of the lard, horsetail grass, dogwood fruits, fruits of the tripartite succession, roots and rhizomes of elecampane, blueberry shoots, galega grass, mulberry leaves and strawberry leaves in a ratio of 1.5: 1.5: 1: 1: 1: 1: 1: 1: 1 (table 4).

Table 4 - The name of the most preferred excipients and their purpose. Name of excipients Appointment Microcrystalline cellulose 101 (MCC 101) Filler α-polyvinylpyrrolidone K25 (α-PVP K25)
PVP K25 Binder, disintegrant Colloidal silicon dioxide (aerosil) Anti-stick, slip Magnesium stearate Sliding Gelatin Capsule material Titanium dioxide (E171) dye Triacetin plasticizer Polysorbate 80 plasticizer

Microcrystalline cellulose 101 (MCC 101) obtained by modification of cotton cellulose is used as a structuring agent, thickener, emulsifier and stabilizer. They dissolve better and are absorbed faster by the body. At the same time, the use of MCC allows the release of biologically active substances gradually, at a controlled rate, for a long time. Microcrystalline cellulose itself is neither digested nor absorbed by the body.

α-polyvinylpyrrolidone K25 (α-PVP K25) - is a polymer of N-vinylpyrrolidone, a free-flowing powder with spherical particle morphology. When used, an optimal balance is achieved between the strength of adhesion and ease of use due to the low viscosity. Have a stable pH value.

Colloidal silicon dioxide (Aerosil). Used as a glidant to increase particle glide. Its small particle size and large specific surface area provide the necessary properties that improve rheological properties during pressing, prevents caking of powdery materials, and promotes the redistribution of moisture in the capsule.

Colloidal silicon dioxide (Aerosil), which is a light white highly dispersed micronized powder with a large specific surface area, which has pronounced adsorption properties. In water, aerosil at a concentration of 1-4% forms jelly-like systems with glycerin, vaseline oil.

Colloidal silicon dioxide (Aerosil) is widely used as a sliding excipient to increase the flowability of a powder mixture, improve tablet coating processes, ensure disintegration and dissolution rate of tablets and a good appearance. Aerosil is used to stabilize suspensions, dry extracts and pills. It provides an even distribution of biologically active substances.

Magnesium stearate is a finely divided white powder that is slightly soapy to the touch. It is a magnesium salt of stearic acid or a mixture of stearic acid salts and synthetic fatty acids. Dissolves in warm alcohol, mixes in oils, practically does not dissolve in water. Magnesium stearate melts at about 88 ° C. Density: 1.02 g / cm³.

Gelatin capsules. Capsules No. 1 were selected as the most suitable in terms of volume for filling with a mass of dry extract that provides dosage of biologically active substances.

To determine and develop the qualitative and quantitative composition of capsules, the results of the quantitative content of biologically active substances in a dry mixture of plant raw materials were used, which are shown in Table 5. The required amount of biologically active substances when used in recommended doses is presented in Table 6.

Table 5 Indicators Content according to ND Content in the sample Flavonoids in terms of rutin,% Not less 0.80 0.93 ± 0.09 Tannins in terms of tannin,% Not less than 4.00 4.45 ± 0.45

Table 6 Index mg Adequate consumption *
Upper admissible consumption level **, mg %
from an adequate level of consumption per day Flavonoids per rutin 7.36 30 * -100 ** 24.50 Tannins in terms of tannin 49.00 300 * -900 ** 16.30

* ^, ** according to the "Unified Sanitary-Epidemiological and Hygienic Requirements for Goods Subject to Sanitary-Epidemiological Supervision (Control)" Chapter II, Section 1, Appendix No. 5.

As the main biologically active substances, plant raw materials contain various groups of flavonoids in terms of rutin and tannins in terms of tannin.

Flavonoids are a group of biologically active substances with a fixed melting point, bitter taste, colorless or colored yellow, red or blue, depending on the pH of the medium. They are readily soluble in polar solvents, methanol, butanol, and alkali solutions.

Flavonoid glycosides are soluble in water, but aglycones are poorly soluble in water. Most flavonoid aglycones are soluble in acetone, ethyl acetate, chloroform, and other hydrophobic solvents.

The presence of phenolic hydroxyl groups determines the acidic properties of flavonoids and their ability to form phenolates in an alkaline medium. Due to the presence of phenolic hydroxyls, flavonoids are easily oxidized. The easy oxidizability of flavonoids promotes the reduction of other substances in the reaction mixture or prevents their oxidation. This property of flavonoids is called antioxidant or antioxidant. In the process of the experimental selection of excipients, it was found that flavonoid antioxidants are capable of strongly inhibiting oxidation processes even in small quantities, which has a significant effect on the stability of the capsule form.

Rutin, is a bioactive polyphenol of the group of vitamins P, is widely used in medicine due to angioprotective, gastroprotective, diuretic, antispasmodic, anti-sclerotic, anti-inflammatory, antiviral effects.

The extremely low solubility of rutin in aqueous media and body fluids creates certain difficulties in creating drugs and carrying out the extraction process, since it is solubility that is one of the main biopharmaceutical characteristics that largely determines the bioavailability of biologically active substances.

It was experimentally found that the solubility of rutin significantly increases in aqueous solutions of polyvinylpyrrolidone with a molecular weight of 8000 and more, human serum albumin and micellar media of cationic surfactants due to the formation of supramolecular complexes.

Surfactants are widely used in pharmaceutical technology as solubilizers, emulsifiers and stabilizers. Polyvinylpyrrolidone is a cationic surfactant, due to the combination of its surface-active and bactericidal properties, this made it possible to increase the stability and release of biologically active substances in the composition of the capsule form in the process of searching for the optimal composition. To increase the bioavailability of rutin and the stability of dietary supplements, Alpha PVP K25 was chosen as an excipient in the form of a binder, which made it possible to improve the solubility and absorption of flavonoids.

Tannins are high molecular weight, genetically related natural phenolic compounds with tanning properties. They are derivatives of pyrogallol, pyrocatechol, phloroglucinol and have a molecular weight of 1000 to 20,000.

Tannins amorphous ampholytes; many dissolve well in water and alcohol, have an astringent taste. In solution, give a neutral / slightly acidic reaction of the medium. In the crystalline state, only catechins are known; they are poorly soluble in cold water, preferably in hot water. Most tannins are highly hygroscopic. In medicinal mixtures, they cannot be mixed with salts of heavy metals, protein substances and alkaloids, as precipitates are formed. By causing partial coagulation of proteins, they form a protective film on the mucous membranes and wound surfaces. On contact with air, tannins are easily oxidized, turning into flobaphenes, which cause the extracts to be dark brown in color.

As a result of the experimental selection of the qualitative and quantitative ratio of biologically active substances and excipients for biologically active additives containing the previously mentioned complex of biologically active substances in the form of a dry extract, the optimal range and ratio of biologically active substances and excipients was established, taking into account all the stated requirements by the authors when solving the assigned tasks and expressed in wt. %: BAS complex in the form of dry extract 30-40%, filler 50-60%, binder, disintegrant 4-6%, anti-stick 0.8-2.2%, sliding 1.2-3.8%.

At the same time, during the installation of the preferred composition, it was recorded that when the range went to the lower side of the biologically active substance in the form of a dry extract and the range for excipients increased, a decrease in bioavailability and a decrease in prolongation were observed, as well as a decrease in the quality of the encapsulated form. A similar situation was observed with the reverse overshoot of the ranges. Thus, failure to comply with the appropriate ranges did not allow achieving the stated technical results. The composition shown in Table 7 should be considered the most preferred embodiment of the invention.

Table 7 Recipe Specification Content per capsule, mg % Capsule contents Biologically active substances BAS complex in the form of dry extract 80,00 36.36 Excipients MCC 101 120,00 54.55 Alpha-PVP K25 11.00 5.00 Aerosil 3.25 1.48 Magnesium stearate 5.75 2.61 Outcomes 220.00 100,00 CAPSUGEL capsules, USA Weight of the filled capsule 290.00-300.00

To select the size of the capsule, the technological characteristics of the mixture for encapsulation containing the extract obtained from plant raw materials were determined, which are presented in table 8.

Table 8 Indicator, units rev. The quantity 1 2 3 4 5 6 The average Particle size ≥100 μm ≥100 μm ≥100 μm ≥100 μm ≥100 μm ≥100 μm ≥100 μm Bulk density before compaction, g / ml 0.34 0.32 0.31 0.30 0.30 0.31 0.33 ± 0.02 Bulk density after compaction, g / ml 0.57 0.58 0.57 0.58 0.57 0.57 0.57 ± 0.02 Angle of repose, degrees 31 thirty 29 thirty thirty 32 30 ± 3 Humidity, % 0.20 0.22 0.25 0.25 0.21 0.19 0.23 ± 0.3 Carr index 10.02 9.20 10.50 9.90 10.10 9.95 10.50 ± 0.3 Hausner index 1.05 1.08 1.09 1.08 1.07 1,110 1.08 ± 0.2

The angle of repose corresponds to 30-32 degrees, the powder was not dusty and spilled out freely from the funnel. The bulk density before compaction is 0.33 and after compaction is 0.57. On the basis of the calculated values of the Carr and Hausner indices, the flowability of the extract was assessed as "very good".

Thus, the obtained quality indicators allow us to conclude that the "flowability" of the mixture for encapsulation increases as a result of mixing the dry extract with the selected auxiliary substances. The most preferred capsule size was chosen size 1.

Example 3. Development of technology for obtaining a dry extract.

To obtain biologically active substances in the form of a dry extract, an aqueous extraction of plant raw materials was carried out by obtaining a liquid extract, followed by filtration, evaporation, water-alcohol purification and drying.

Description of the technological process.

1. Obtaining a liquid extract.

On a laboratory scale, 700.0 g of plant material is weighed, placed in an ultrasonic extractor, preferably NO-538, and 7500 ml of extractant is poured in, preferably purified water at 70–80 ° C, the extraction time is approximately 30 minutes. The temperature of the water circuit is about 60-70 ° C. After the completion of the extraction process, the raw material is squeezed out, the liquid extract is filtered through a sieve with a mesh diameter of preferably 355 µm, and then preferably 250 µm. The coefficient of water absorption of plant materials was calculated experimentally and amounted to 3.2. The volume of the obtained liquid extract was approximately 6100 ml.

2. Evaporation of the liquid extract.

A 1000 ml flask is filled with the extract to 2/3 of its volume and evaporated on any rotary evaporator, preferably BUCHI R-300, at a water bath temperature of 60 ° C. The flask rotation speed is 80 rpm. The initial vacuum is 180 mbar, gradually decreasing in 5 mbar steps, down to 30 mbar within 20 minutes, avoiding the boiling point. The total duration of the extractant stripping process is 45 minutes. The resulting volumes of thick extracts are combined. The total volume of the thick extract is 1000 ml.

3. Cleaning

The resulting volume of the thick extract is transferred to a 2000 ml flask. Ethanol 96% in a volume of 200 ml is added to the thick extract and mixed. Then filtered, preferably filtering in a Bunsen flask through a six-layer gauze filter. The volume of the purified thick extract is 1100 ml.

4. Getting dry extract

The purified thick extract is poured into 550 ml drying trays and dried in an oven at 70 ° C for 26 hours. After 26 hours, check the residual moisture content of the dry extract, its value should be less than 5%. At a residual moisture content of more than 5%, the extract is dried for about 4 hours at a temperature of 70 ° C. The obtained dry extract is ground using a mill for dry grinding of solid and brittle substances for about 30-40 seconds, a rotation speed of 6000 rpm to a particle size passing through a sieve with a mesh diameter of 250 microns. The dry extract weight is 150.00 g.

Example 4. Encapsulation of biologically active substances in the form of a dry extract.

To obtain a mixture for encapsulation on an analytical balance, exact weighed portions of the components of the capsule are weighed (Table 7). The mixture is stirred, preferably in a glass beaker with an overhead stirrer for 10 minutes.

Filling of capsules is carried out using any suitable capsule filling machine for this procedure, preferably a manual Optima Aluminum capsule filling machine (Farmalabor Tech, Italy), and the most preferred capsule option is hard gelatin capsules No. 1, manufactured by Capsugel.

Dosing into capsules is carried out using any device known in the art suitable for this operation, however the preferred embodiment is a manual capsule filling machine, more preferably Optima Aluminum. It dispenses in four sequential stages: insertion of empty capsules, separation, filling and reassembly.

The mixture, previously weighed on a balance with an accuracy of 0.0001 g in the amount of 220.00 mg, is dosed into each capsule, then the caps are installed and the locking device is fixed.

Example 5. Determination of quality indicators of a dietary supplement.

Thin layer chromatography. Determination of the authenticity of flavonoids.

Norm: The chromatogram of the test solution should show: the adsorption zone with fluorescence of yellow-orange color approximately at the level of the adsorption zone of CO (standard sample) rutin, the adsorption zone with fluorescence of bright yellow color below the adsorption zone of CO rutin; detection of additional 3-4 adsorption zones is allowed, including the adsorption zone with yellow fluorescence above the CO adsorption zone of rutin.

Qualitative reaction to tannins.

To 1.00 g of the sample, add 10 ml of alcohol (30%) and heat in a water bath under reflux for 30 minutes. Cool and filter. To 1 ml of the filtrate add 2 ml of a 10% solution of vanillin in hydrochloric acid. A red color appears.

The uniformity of the mass of the capsules was determined in accordance with General Pharmacopoeia Monograph 1.4.2.0009.15 "Uniformity of the mass of dosage forms" using an electronic balance. The average weight was determined by weighing 20 dosage units (unopened capsules). Each unit was weighed separately to the nearest 0.001 g and the average weight was calculated.

- Opened the capsules and removed its contents as completely as possible. Weighed the shell. The mass of the contents of each capsule was calculated as the difference between weighings. The determination was repeated on the 19 remaining capsules.

Norm: No more than 2 individual masses may deviate from the average mass of no more than 10.0% - for capsules with contents weighing less than 290 mg.

Disintegration of capsules. (OFS.1.4.1.0005.15 "Capsules"). The therapeutic effect of dietary supplements depends not only on the dosage of the active substance, but also on the speed and completeness of their release from the capsule. In a liquid medium, the capsules first disintegrate into separate fragments, from which the release of the active substance then begins. In accordance with modern requirements, capsules must combine sufficient mechanical strength required for automatic filling, packaging and transportation, and disintegration in an aqueous medium, which meets the requirements of the State Fund of the Russian Federation.

Determination of disintegration was carried out on a “swinging basket” device ED-2 SAPOx from Electrolab, India. The volume of the medium is 800 ml. Three media were used: 0.1 M hydrochloric acid solution with pH 1.2; acetate buffer pH 4.5; and phosphate buffer pH 6.8. Medium temperature (37 ± 0.5) ° С, volume - 800 ml, the experiment was carried out without using caps.

Dissolution media were prepared in accordance with General Pharmacopoeia Monograph 1.3.0003.15 "Buffer solutions".

To prepare 1 liter of 0.1 M hydrochloric acid solution with pH 1.2, a standard titer was used (ZAO Uralkhiminvest). The content of the fixanal was brought to a volume of 1000 ml with purified water, with stirring on a magnetic stirrer (RO5, IKA, Germany) for an hour while heating to a temperature of 40 ° C.

To prepare 1 liter of acetate buffer with pH 4.5, 63.0 g of anhydrous sodium acetate is dissolved in water, 90 ml of diluted acetic acid (30%) is added, the pH value is adjusted to 4.5 potentiometrically with acetic acid 30%, and the volume is adjusted with purified water to 1000 ml. Then, with stirring on a magnetic stirrer (RO5, IKA, Germany) for an hour while heating to a temperature of 40 ° C.

To prepare 1 l of potassium phosphate buffer with pH 6.8 51.0 ml of 27.2 g / l potassium dihydrogen phosphate solution is mixed with 49.0 ml of 71.6 g / l disodium hydrogen phosphate solution. If necessary, adjust the pH to 6.8 potentiometrically with a stock solution of potassium dihydrogen phosphate or disodium hydrogen phosphate. Then, with stirring on a magnetic stirrer (RO5, IKA, Germany) for an hour while heating to a temperature of 40 ° C.

Norm: unless otherwise indicated in the pharmacopoeial monograph or regulatory documentation, capsules should disintegrate in water in no more than 30 minutes.

Dissolution test. The "Dissolution" test was carried out according to OFS.1.4.2.0014.15, GF XIV on an apparatus of the "Paddle stirrer" type (EDT-08Lx, Electrolab, India) at a stirrer rotation speed of 50 rpm, directly into each of the six vessels with the dissolution medium one capsule at a time was placed before the stirrer began to rotate.

In accordance with modern requirements, the study of the comparative kinetics of dissolution was carried out in three media: with a pH of 1.2 (0.1 M hydrochloric acid solution); with pH 4.5 (acetate buffer) and with pH 6.8 (phosphate buffer). The volume of the dissolution medium is 500 ml (pH = 1.2) and 800 ml (pH = 4.5 and pH = 6.8), the temperature of the dissolution medium is (37 ± 0.5) ° C. Dissolution media were prepared in accordance with General Pharmacopoeia Monograph 1.3.0003.15 "Buffer solutions", according to the method described above in the section "Disintegration of capsules".

The dissolution profiles should consist of at least three points, excluding the zero point; therefore, samples were taken after 5, 10, 15, 30, and 45 minutes in portions of 10 ml. The same volume of the corresponding buffer solution was added to the dissolution medium to maintain volume. Sampling was carried out from the area of the dissolution vessel located between the surface of the dissolution medium and the upper part of the stirrer blade and at a distance of at least 1 cm from the walls of the dissolution vessel.

Requirements: unless otherwise specified in the regulatory documentation, the amount of active substances released into the dissolution medium within 45 minutes must be at least 75% (Q) of the declared content.

Definition of biologically active substances

Determination of the sum of flavonoids in terms of rutin. The quantitative determination of flavonoids is based on the spectrophotometric method at a wavelength of 415 nm of the products of their interaction with a solution of aluminum chloride and spectrophotometry at a wavelength of 495 nm of the products of their interaction with 2,4-dinitrophenylhydrazine.

The principle of the colorimetric method based on the interaction with aluminum chloride is that the reagent forms acid-stable complexes with the C-4 keto group and with the C-3 or C-5 hydroxyl group of flavones and flavonols, which have absorption maxima in the wavelength range 415 -440 nm.

The principle of interaction with 2,4-dinitrophenylhydrazine is based on its reaction with ketones and aldehydes to form 2,4-dinitrophenylhydrazones. Consequently, flavones, flavonols and isoflavones with C2-C3 double bonds are unable to react with 2,4-dinitrophenylhydrazine, while hydrazones and flavonones form compounds having an absorption maximum at 495 nm. The results of the analysis are presented in Table 9.

Table 9 Sample Content, mg / g Flavonols and their glycosides Flavones and their glycosides Chalcones and their glycosides Flavanones and
their glycosides Flavonoid amount 1 18.72 4.40 - - 23.12 2 18.57 4.33 - - 22.90 3 17.02 4.28 - - 21.30 4 17.77 4.34 - - 22.11 5 18.58 4.31 - - 22.89 6 20.57 3.29 - - 23.86

Determination of the amount of tannins in terms of tannin.

The quantitative determination of tannins is based on the method of titration with a permanganate solution until golden yellow coloration. The results of the analysis are presented in Table 10.

Table 10 Sample 1 2 3 4 5 6 The content of tanning
substances, mg / g 310.20 305.05 309.12 307.63 308.80 309.99

Microbiological purity. In terms of microbiological indicators, the dietary supplement must comply with the requirements of clause 10.10 of Chapter II, section 1 "Unified sanitary-epidemiological and hygienic requirements for goods subject to sanitary-epidemiological supervision (control)".

The results of determining indicators for the quality of a biologically active additive are shown in table 11.

Table 11 Indicators results 1 2 3 4 5 6 Description acc. acc. acc. acc. acc. acc. Authenticity acc. acc. acc. acc. acc. acc. Quantitative determination, mg 2.05 ± 0.18; 12.51 ± 1.20 2.00 ± 0.18; 13.52 ± 1.20 1.95 ± 0.18; 13.20 ± 1.20 1.95 ± 0.18; 12.91 ± 1.20 1.82 ± 0.18; 11.84 ± 1.20 1.84 ± 0.18; 11.95 ± 1.20 Mass uniformity, mg 295.10 293.00 291.15 291.10 292.20 290.10

As a result, the developed dietary supplement of encapsulated form meets all of the above indicators. During development, taking into account the dosage of each capsule, it was determined that the recommended dosage regimen is 2 capsules 2 times a day. The capsule form and dosage regimen allows maintaining high medical compliance and receiving the optimal amount of flavonoids and tannins, as well as providing therapeutic and prophylactic effects on the gastrointestinal tract, liver, kidneys and, in particular, the pancreas.

Claims (10)

1. Dietary supplement of the encapsulated form, containing a complex of biologically active substances (BAS) in the form of a dry extract as an active component, including the roots of the lard, horsetail herb, cornelian cherries, fruits of the tripartite succession, roots and rhizomes of elecampane, blueberry shoots ordinary, gellegi grass, mulberry leaves and strawberry leaves in a ratio of 1.5: 1.5: 1: 1: 1: 1: 1: 1: 1, and a complex of excipients, including a filler, binder, disintegrant, anti-stick, sliding. 2. Biologically active additive of the encapsulated form according to claim 1, characterized in that the complex of biologically active substances in the form of a dry extract and a complex of excipients are represented by the following composition wt.%: Complex of biologically active substances in the form of a dry extract 30-40%, filler 50-60%, binder, disintegrant 4-6%, anti-stick 0.8-2.2%, sliding 1.2-3.8%. 3. Dietary supplement of the encapsulated form according to PP. 1, 2, characterized in that microcrystalline cellulose 101 (MCC 101) is selected as the filler. 4. Dietary supplement of the encapsulated form according to PP. 1, 2, characterized in that α-polyvinylpyrrolidone K 25 (α-PVP K25) is selected as a binder, disintegrant. 5. Dietary supplement of the encapsulated form according to PP. 1, 2, characterized in that colloidal silicon dioxide is selected as the anti-stick. 6. Dietary supplement of the encapsulated form according to PP. 1, 2, characterized in that magnesium stearate is selected as the slide. 7. Dietary supplement of the encapsulated form according to PP. 1-6, characterized in that the composition is preferable with the following ratio of components, wt%: BAS complex in the form of dry extract 36.36 MCC 101 54.55 Alpha-PVP K25 5.00 Colloidal silicon dioxide 1.48 Magnesium stearate 2.61 8. A method of obtaining a biologically active supplement of the encapsulated form according to PP. 1-7, which includes the following steps: obtaining a liquid extract followed by evaporation, purifying the extract followed by obtaining a dry extract, mixing with auxiliary substances and encapsulation. 9. The use of a dietary supplement of the encapsulated form according to PP. 1-7 as a source of flavonoids and tannins.