RU2516932C2 - Biologically active food additive with hepato-protective and immunostimulating properties - Google Patents

Abstract

FIELD: food industry.

SUBSTANCE: composition with hepato-protective and immunostimulating properties contains oxygenated dextran with molecular weight equal to 40-70 kDa and a vegetal raw material component chosen from the following group: dry Saint-Mary-thistle fruits extract, dry hill-growing saltwort extract, dry purple echinacea herb extract as well as microcrystalline cellulose as a physiologically acceptable filler, taken in a specified quantity.

EFFECT: hepato-protective and immunostimulating properties enhancement.

1 tbl, 8 ex

Description

The invention relates to the food and medical industries and can be used to create biologically active therapeutic and prophylactic compositions containing medicinal plants and their extracts, as well as to create functional foods that increase the immunobiological resistance of the human body.

To enrich the diet, macro- (proteins, fats, carbohydrates, mineral salts) and micronutrients (trace elements, water- and fat-soluble vitamins) are used in food with biologically active food supplements, the assortment and spectrum of effects of which are very diverse. Supplements to food, accumulating a small amount of high biological activity, are able to affect deep metabolic processes.

As a promising source of plant materials for creating biologically active additives containing physiologically functional ingredients, milk thistle, echinacea, and hodgepodge, with hepatoprotective and immunostimulating properties, are of practical interest.

For example, a biologically active food supplement is known, which is a complex of plant materials, inosine, succinic acid and an auxiliary component - magnesium stearate. As components of plant origin, dry extracts from prickly eleutherococcus, spotted milk thistle, creeping Tribulus and green tea are used (patent RU 2449600, op. September 27, 2010).

The disadvantage of dietary supplements is insufficiently expressed hepatoprotective and immunostimulating effect.

Known biologically active food supplement "Lactofit", which is characterized by the fact that Jerusalem artichoke, beets, carrots, pumpkins, germinated in milk whey pumpkin seeds, milk thistle, chickpeas are subjected to extraction with honey. Then the honey extract is mixed with lactulose, in which malic acid is previously dissolved, and pumpkin and milk thistle oil are added (patent RU 2400107, op. September 27, 2010).

The disadvantage of dietary supplements is insufficiently expressed hepatoprotective and immunostimulating effect.

A biologically active food supplement consisting of two tablets is known, the composition of the first tablet is the same for all three variants of the invention and includes the following components: bromelain, sodium ascorbate, iron pyrophosphate, hodgepodge hill extract, papain, zinc citrate, boron chelate, sodium metasilicate, milk thistle extract, quercetin, rutin, ginkgo biloba extract, hesperidin, nicotinamide, tocopherol acetate, superoxide dismutase, retinol acetate, manganese sulfate, dihydroquercetin, calcium pantothenate, copper citrate, chole altsiferol, pyridoxine hydrochloride, riboflavin, beta-carotene 20, thiamine mononitrate, coenzyme q _10, folic acid, chromium picolinate, potassium iodate, sodium selenite, sodium molybdate, ammonium vanadate, biotin, silver sulfate, cyanocobalamin and a filler. The composition of the second tablet varies from variant to variant, depending on the gender or age characteristics of the person. All components of the tablets are selected in a certain ratio (patent RU 2352147, op. 04/20/2009). The invention allows to obtain dietary supplements for food, increasing immunity and resistance to stress.

The disadvantage of dietary supplements is the multicomponent composition and insufficiently expressed hepatoprotective and immunostimulating effect.

Known biologically active food supplement to normalize the function of the thyroid gland and increase the immune status of the body, containing the roots and rhizomes of the white cinquefoil, or the ground part of the white cinquefoil, or their mixture, as well as purple coneflower and kelp in a certain ratio of components (patent RU 2446815, op . 04/10/2012).

The disadvantage of dietary supplements is the lack of hepatoprotective action.

The closest to the claimed prototype is a biologically active food supplement for the prevention of immune system weakening, made in tablet form containing dry extract of echinacea purpurea and physiologically acceptable excipients: magnesium stearate, finely divided powder of dry herb echinacea, ascorbic acid and microcrystalline cellulose in the ratio of ingredients, wt.%: dry extract of herbs and / or roots of Echinacea 10.0-40.0; Echinacea dry herb powder 20.0-70.0; ascorbic acid 1.0-4.0; magnesium stearate 0.3-1.0; microcrystalline cellulose - up to 100%. The additive is made from powders of ingredients, crushed to particle sizes less than 500 microns (patent RU 2182011, op. 10.02.2005).

The disadvantage of dietary supplements is the lack of hepatoprotective action and insufficiently expressed immunostimulating effect.

The present invention is the development of a new effective and affordable composition with hepatoprotective and immunostimulating activity.

The technical result is an increase in hepatoprotective and immunostimulating activity.

The problem is achieved in that the composition of the claimed composition as the main active ingredient includes oxidized dextran with an average molecular weight (mm) of 40-70 kDa, and as an additional component that synergistically enhances the biological properties of the claimed composition, includes a component of plant origin, containing bioflavonoids selected from the group: the fruits of milk thistle (mainly silymarin), grass of the hodgepodge, grass and / or roots of Echinacea purpurea. As components of plant origin, mainly dry extracts of the above plants are used.

The proposed composition contains the following components, wt.%:

Oxidized Dextran with MM 40-70 Yes 1.0-10.0 Plant component 1.0-10.0 Physiologically acceptable excipient up to 100

As the excipient, any pharmaceutically acceptable excipients, preferably microcrystalline cellulose, can be used.

The inventive composition can be performed in any technologically acceptable form used in the manufacture of dietary supplements intended for use per os in solid form (tablets, capsules, powders, pills, boluses).

The choice of the qualitative composition of the components of the composition and their quantitative ratio is due to the following considerations.

The main component of the proposed composition for physiological effects on the body is oxidized dextran, which is an oxidized form of a polysaccharide with the ability to stimulate the cellular immunity, in particular phagocytosis.

It can be obtained by known methods based on the chemical or radiation oxidation of dextran. In particular, oxidized dextran can be obtained chemically, for example, by isolating dextran fractions from the commercial preparation Reopoliglukin, then oxidizing the dextran with sodium periodate and precipitating the oxidized dextran with ethanol (patent RU 2087146, on. 08.20.1997). Modifications of this method are known that differ in using additional methods for purifying oxidized dextran from impurities (patent RU 2163120, op. 02.20.2001). Potassium permanganate is also used as an oxidizing agent for dextran (EA patent No. 011718, op. 04/28/2009).

In accordance with the invention, other desirable components of the composition of the invention are dry extracts from spotted milk thistle (mainly silymarin), hill hodgepodge grass, herbs and / or roots of purple coneflower, included in the dietary supplement individually or in different combinations (ready-made substances of a dry plant extract are used, produced by any enterprise specializing in the production of dry plant extracts).

Dry extract from the fruits of milk thistle contains tyramine and histamine, has a choleretic and hepatoprotective effect.

Dry extract from the herb and / or roots of purple coneflower contains flavonoids, hydroxycinnamic acids, polysaccharides, phenolic glycoside (echinacoside), saponins, tannins, resins, essential oil; It has an immunostimulating, anti-inflammatory, antimicrobial, antiviral effect and is used for viral and bacterial infections of various localization, with reduced immunity, liver diseases, trophic ulcers, eczema.

The dry extract from the grass of Solyanka hillock contains flavonoids and flavonoid glycosides, flavonolignans, sterols and sterling glycosides, carbohydrates and their esters, alkaloids, quaternary bases, amino acids, saturated and unsaturated fatty acids, mineral components: potassium, calcium, magnesium, phosphorus, aluminum, aluminum , trace elements: boron, cadmium, cobalt, copper, molybdenum, nickel. Among the mineral components, a particularly high content of macronutrients such as potassium, calcium, phosphorus, magnesium is noted, it has a pronounced hepatoprotective effect.

Microcrystalline cellulose (MCC) used as a filler serves as a dietary fiber capable of activating the motor-secretory and evacuation function of the intestine. MCC fibers help to eliminate toxic substances, metabolic products, cholesterol, heavy metals and radionuclides from the body. MCC promotes the exchange of fats and lipoprotein in the blood.

The inclusion of MCC as a component (filler) of the proposed dietary supplement makes it possible to enhance the effectiveness of the latter due to the ability of the plant components of lectins, metal-containing protein complexes, to partially destroy the polymer molecules of MCC in the gastrointestinal tract. The oligomers formed in this case are characterized by increased sorption ability and bioavailability, which allows them to sorb the biologically active substances of plant components on their surface, to promote their better penetration into the blood and lymph, and also to contribute to improved detoxification of the body and normalization of the blood formula.

The results of the study of the immunostimulating and hepatoprotective properties of the claimed composition on in vitro and in vivo models are presented in table 1, which shows that the claimed composition in comparison with the prototype and analogues has a higher biological activity. Moreover, in the inventive composition containing in addition to oxidized dextran plant extracts, bioflavonoids, the effect of the synergistic action of the components is clearly visible.

The non-obviousness of the result follows from modern ideas about the biological properties of polysaccharides and, in particular, dextrans. Currently, it is known that dextrans have detoxification properties, but these properties appear only with parenteral administration. In modern scientific and technical literature there is no data on the ability of polysaccharides, in particular dextrans, to penetrate into the systemic circulation, through the walls of the gastrointestinal tract. On the contrary, it is not obvious from the existing ideas about the structure and function of the intestinal epithelium that large molecules, such as proteins and polysaccharides, can be absorbed into the systemic circulation and provide a therapeutic effect. In the claimed technical solution, the formulations of the composition according to the main component - oxidized dextran, are experimentally selected in such a way that at concentrations of oxidized dextran less than 1% its enteric bioavailability is extremely low, and at concentrations of more than 10% its bioavailability does not increase and remains unchanged. When introducing into the formulation of the composition of additional components from plant materials that provide a synergistic effect, their concentration should not exceed 10%, since at higher concentrations the risk of developing allergic reactions increases.

The study of the immunostimulating effect of the claimed composition was carried out according to a known method for assessing the number (%) of adhered (flattened) macrophages during cultivation of peritoneal macrophages obtained by lavage of the abdominal cavity of mice with physiological saline 8 days after daily oral administration of the claimed composition (In Vitro Effects of Molecular Nanosomal Hybrid Compositions with Oxidized Dextrans, Conjugated with Isonicotinic Acid Hydrazine on Peritoneal Macrophages, Shkurupii VA, Archipov SA et all., Bulletin of Experimental Biology and Medicine - 2008 - Vol.146. - No.5 - P.627-629). As controls used well-known dietary supplement (prototype) or extracts from plant materials.

As a methodology for studying the hepatoprotective effect of the claimed composition, the method of liver damage with carbon tetrachloride ["Guide to the experimental (preclinical) study of new pharmacological substances" under the general editorship of R.U. Khabrieva, M, 2005.]. The inventive composition was administered in a dose of 0.2 ml of a 10% aqueous suspension per os to mice before inoculation with carbon tetrachloride for 5 days and after for 3 days. Then the mice were euthanized under ether anesthesia and a morphological examination of the liver was performed after staining of the histological sections with hematoxillin / eosin. A morphological study of histological sections evaluated morphometrically the bulk density of destructive changes (necrosis) in the liver (in%) and the numerical density of binuclear hepatocytes (regeneration rate) (in%). As controls, they used dietary supplements (prototype), as well as dry extracts of grass of hodgepodge, Echinacea or milk thistle).

The present invention is illustrated by the following examples of specific performance.

Example 1

The composition contains the following components, wt.%:

Oxidized Dextran with MM 40 kDa 1,0 Microcrystalline cellulose (filler) 99.0

1 g of oxidized dextran with mM 40 kDa and 99 g of microcrystalline cellulose are mixed. The mixture is subjected to wet granulation, drying, and then 100 mg tablets are obtained from the granulate on a tablet press. The yield of the finished product, taking into account losses during granulation and pressing, is 90%.

Example 2

The composition contains the following components, wt.%:

Oxidized Dextran with MM 40 kDa 5,0 Microcrystalline cellulose (filler) 95.0

5 g of oxidized dextran are mixed with mM 40 kDa and 95 g of microcrystalline cellulose. The mixture is subjected to wet granulation, drying, and then 100 mg tablets are obtained from the granulate on a tablet press. The yield of the finished product, taking into account losses during granulation and pressing, is 92%.

Example 3

The composition contains the following components, wt.%:

Oxidized Dextran with MM 70 kDa 10.0 Microcrystalline cellulose (filler) 90.0

10 g of oxidized dextran are mixed with mM 70 kDa and 90 g of microcrystalline cellulose. The mixture is subjected to wet granulation, drying, and then 100 mg tablets are obtained from the granulate on a tablet press. The yield of the finished product, taking into account losses during granulation and pressing, is 90%.

Example 4

The composition contains the following components, wt.%:

Oxidized Dextran with MM 70 kDa 5,0 Dry milk thistle extract 5,0 Dry Echinacea Herb Extract 1,0 Microcrystalline cellulose (filler) 89.0

5 g of oxidized dextran are mixed with mM 40 kDa, 5 g of dry extract from milk thistle, 1 g of dry extract from Echinacea herb and 89 g of microcrystalline cellulose. The mixture is subjected to wet granulation, drying, and then 100 mg tablets are obtained from the granulate on a tablet press. The yield of the finished product, taking into account losses during granulation and pressing, is 89%.

Example 5

The composition contains the following components, wt.%:

Oxidized Dextran with MM 40 kDa 5,0 Silymarin (sum of milk thistle flavonoids) 1,0 Microcrystalline cellulose (filler) 94.0

5 g of oxidized dextran are mixed with mM 40 kDa, 1 g of silymarin and 94 g of microcrystalline cellulose. The mixture is subjected to wet granulation, drying, and then 100 mg tablets are obtained from the granulate on a tablet press. The yield of the finished product, taking into account losses during granulation and pressing, is 95%.

Example 6

The composition contains the following components, wt.%:

Oxidized Dextran with MM 70 kDa 5,0 Silymarin (sum of milk thistle flavonoids) 10.0 Microcrystalline cellulose (filler) 85.0

5 g of oxidized dextran are mixed with mM 70 kDa, 10 g of silymarin and 85 g of microcrystalline cellulose. The mixture is subjected to wet granulation, drying, and then 100 mg tablets are obtained from the granulate on a tablet press. The yield of the finished product, taking into account losses during granulation and pressing, is 95%.

Example 7

The composition contains the following components, wt.%:

Oxidized Dextran with MM 70 kDa 10.0 Dry extract of grass Solyanka hill 1,0 Microcrystalline cellulose (filler) 89.0

10 g of oxidized dextran are mixed with mM 70 kDa, 1 g of dry extract from grass of hodgepodge, 89 g of microcrystalline cellulose. The yield of the finished product, taking into account losses during granulation and pressing, is 97%.

Example 8

The composition contains the following components, wt.%:

Oxidized Dextran with MM 70 kDa 5,0 Dry extract of Echinacea purpurea herb 10.0 Microcrystalline cellulose (filler) 85.0

5 g of oxidized dextran are mixed with mM 70 kDa, 10 g of dry extract from Echinacea herb and 85 g of microcrystalline cellulose. The mixture is subjected to wet granulation, drying, and then granulate is poured into 100 mg gelatin capsules. The yield of the finished product, taking into account losses during granulation and pressing, is 87%.

The results of biological testing of the claimed composition in comparison with the prototype and minor components are presented in table 1.

As can be seen from table 1, the claimed compositions of the composition containing only oxidized dextran have a higher immunostimulating and hepatoprotective activity compared to the prototype. The inventive composition containing in addition to oxidized dextran dry plant extracts containing bioflavonoids due to the synergistic biological action of the components has a more pronounced immunostimulating effect both in comparison with the prototype and in comparison with minor additional components (plant extracts).

The use of the invention allows to obtain a dosed drug that meets the status of biologically active additives, consisting of a minimum number of highly effective components with maximum preservation of active substances, with hepatoprotective and immunostimulating properties.

Table 1 No. p / p Test sample The numerical density of binuclear hepatocytes,% Bulk density of destructive changes (necrosis) in the liver,% Adhesive activity of peritoneal macrophages,% spread macrophages one. Composition (example 1) 8 ± 1.3 60.2 ± 1.9 84.3 ± 1.9 2. Composition (example 2) 10 ± 1,1 55 ± 2,3 85.4 ± 3.4 3. Composition (example 3) 8 ± 1,1 61 ± 3.4 90 ± 5.1 four. Composition (example 4) 19 ± 1,5 50 ± 2.5 95 ± 4.2 5. Composition (example 5) 19 ± 1,1 50 ± 2.2 93 ± 7.8 6. Composition (example 6) 18 ± 2.1 45 ± 3.6 95 ± 2.7 7. Composition (example 7) 12 ± 1.8 50 ± 4,5 94 ± 5.1 8. Composition (example 8) 5 ± 2,3 69 ± 1,2 97 ± 2.1 9. BAA prototype (control 1) 3 ± 1,1 74.1 ± 2.9 65 ± 1.9 10 Milk Thistle Extract (Control 2) 4 ± 1,1 78.2 ± 1.8 50 ± 2,3 eleven Hillwort herb extract (control 3) 6 ± 1,2 74.8 ± 2.3 64 ± 2.1 12 Echinacea herb extract (control 4) 2 ± 1,6 82 ± 3.4 58 ± 1.8

Claims (1)

A composition having hepatoprotective and immunostimulating properties, containing oxidized dextran with a molecular weight of 40-70 kDa, a component from plant materials, selected from the group: dry extract of the fruit of milk thistle, dry extract from the herb Solyanka solanum, dry extract from the herb Echinacea purpurea, as well as microcrystalline cellulose as a physiologically acceptable filler, in the following ratio of components, wt.%:
Oxidized dextran with a molecular weight of 40-70 kDa 1.0-10.0 Raw Material Component 1.0-10.0 Microcrystalline cellulose up to 100