RU2623152C9 - Composition with hepatoprotective and immunostimulating properties - Google Patents

Abstract

FIELD: pharmacology.

SUBSTANCE: invention can be used to create biologically active therapeutic and prophylactic compositions containing dry and liquid extracts of medicinal plants, functional foods that increase body immunobiological resistance and have hepatoprotective effect. A composition having hepatoprotective immunostimulating properties comprises modified dextran and a physiologically acceptable excipient. Dextranal with a molecular weight of 20-75 kDa is used as the modified dextran at a certain ratio of components.

EFFECT: composition has a more effective hepatoprotective and immunostimulating activity and can be manufactured in any technologically acceptable form.

4 cl, 1 tbl, 6 ex

Description

The invention relates to the food and pharmaceutical industries, where it can be used to create biologically active therapeutic and prophylactic compositions containing dry and liquid extracts of medicinal plants, functional foods that increase the immunobiological resistance of the body and have a hepatoprotective effect.

Currently, there is a wide range of various biologically active food additives (BAA) on the market, designed to enrich the diet with macro- and micronutrients that have different types of effects on the body.

Milk thistle and echinacea, which have a hepatoprotective and immunostimulating effect, are similar in type of action, and that is why dietary supplements based on them are of practical interest to us.

For example, a biologically active food supplement is known according to the patent of the Russian Federation No. 2446815 (publication date 04/10/2012), which has an effect on the thyroid gland and immunity. It contains cinquefoil, echinacea and kelp.

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

Known biologically active food supplement according to the patent of the Russian Federation No. 2449600 (publication date 05/10/2012), consisting of inosine, succinic acid, magnesium stearate, eleutherococcus and milk thistle.

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

Known biologically active food supplement according to the patent of the Russian Federation No. 2182011 (publication date 10.05.2002), which is a composition of dry extract of echinacea and physiologically acceptable excipients: magnesium stearate, dry powder of echinacea herb, ascorbic acid and microcrystalline cellulose.

The disadvantage of dietary supplements is the lack of a hepatoprotective effect and an insufficiently pronounced immunostimulating effect.

The closest to the claimed - the prototype - is a biologically active food supplement according to the patent of the Russian Federation No. 2516932 (publication date 05/20/2014), the components of which are: modified dextran, dry plant material and a physiologically acceptable filler.

The disadvantages of this dietary supplement is an insufficiently pronounced immunostimulating and hepatoprotective effect, requiring the mandatory content of functional herbs known for their action, such as milk thistle, echinacea. The dietary supplement is produced only in dry form, which may cause restrictions on intake for people with diseases of the gastrointestinal tract.

The objective of the present invention is to develop a new, more effective composition that has hepatoprotective and immunostimulating activity with the possibility of performing in any technologically acceptable form, intended for oral administration in solid (tablets, capsules, powders, briquettes) or liquid (syrups, extracts, solutions, cocktails, suspensions, emulsions) forms.

The problem is solved by the proposed formulation of a biologically active food supplement, which includes a modified dextran and a physiologically acceptable filler, while dextranal with a molecular weight of 20-75 kDa, obtained by mechanoactivation of dextran, is used as a modified dextran, in the following ratio, % wt. : dextranal with m.m. 20-75 kDa - 0.5-10.0, physiologically acceptable filler - up to 100.

In particular, the physiologically acceptable excipient is dry or aqueous extracts of plant materials, microcrystalline cellulose, or mixtures thereof.

In particular, it contains a combination of extracts of milk thistle, burdock root and immortelle or a combination of extracts of rose hips and burdock root as plant extracts.

In particular, the physiologically acceptable excipient is a liquid, emulsion, suspension, paste.

In particular, water, saline or buffer solution is chosen as the liquid.

Components can be introduced into the composition of the additive in different combinations or separately.

The claimed composition can be made in any technologically acceptable form used in the manufacture of dietary supplements intended for oral administration (tablets, capsules, powders, briquettes, syrups, extracts, solutions, cocktails, suspensions).

The main component of the proposed additive is dextranal - the active form of dextran, obtained by its modification, which ensures high reactivity and activity of the additive and allows for more efficient delivery of active substances to the cells of the body and stimulates the cellular link of immunity, in particular phagocytosis.

Dextranal is obtained by mechanoactivation of dextran, for example, using devices such as a rotary pulsation apparatus, a disintegrator, an ultrasonic apparatus, etc.

Conducted studies have determined the effective level of dextranal content from 0.5 to 10% of the mass. An increase in the concentration of dextranal over 10% leads to a significant increase in the cost of dietary supplements, without leading to a significant improvement in the state of the body. When the concentration of dextranal in dietary supplements is less than 0.5%, there are no noticeable effects from its use.

The choleretic and cholekinetic effect of action revealed in the main group, the decrease in the activity of the inflammatory process, the stabilization of the colloidal composition of bile reduce the enterohepatic circulation of hydrophobic bile acids, thereby preventing their toxic effect on the membranes of hepatocytes, the epithelium of the bile ducts, which ultimately reduces cholestasis-mediated immunosuppression. Inactivation of lipid peroxidation processes helps stabilize the lipid layer of hepatocyte membranes and reduce nonspecific damage to the inner mitochondrial membrane. Both mechanisms determine the possibility of inhibition of hepatodystrophy processes.

Thus, studies have shown that dietary supplements based on dextranal have an immunomodulatory, hepatoprotective effect.

Variants of food compositions containing the claimed biologically active additive are given in examples of a specific implementation.

Specific Implementation Examples

Example 1

Biologically active additive containing, % wt.:

Dextranal with m.m. 20-75 kDa 0.5 Microcrystalline cellulose 99.5

Example 2

Biologically active additive containing, % wt.:

Dextranal with m.m. 20-75 kDa 10.0 Sugar 0.5 Water 89.5

Example 3

Biologically active additive containing, % wt.:

Dextranal with m.m. 20-75 kDa 0.5 Milk thistle extract 3.5 Burdock Root Extract 1.5 immortelle extract 2.5 Microcrystalline cellulose 92.0

Example 4

Biologically active additive containing, % wt.:

Dextranal with m.m. 20-75 kDa 10.0 Milk thistle extract 3.0 Burdock Root Extract 0.5 immortelle extract 0.5 Saline 86.0

Example 5

Biologically active additive containing, % wt.:

Dextranal with m.m. 20-75 kDa 0.5 Rose hip extract 2.5 Burdock Root Extract 1.0 Microcrystalline cellulose 96.0

Example 6

Biologically active additive containing, % wt.:

Dextranal with m.m. 20-75 kDa 10.0 Rose hip extract 0.5 Burdock Root Extract 0.5 buffer solution 99.0

A preclinical study of the immunostimulating effect of the proposed solution, as in the prototype, was carried out according to a well-known method for assessing the number (%) of adherent (spread) macrophages during the cultivation of peritoneal macrophages obtained by lavage of the abdominal cavity of mice with saline 8 days after a single daily oral administration of the claimed biologically active additives (In Vitro Effects of Molecular Nanosomal Hybrid Compositions with Oxidized Dextras, Conjugated with Isonicotinic Acid Hydrazine on Peritoneal Macrophages, Shkurupii VA, Archipov SA et all, Bulletin of Experimehtal Biology and Medicin - 2008 - Vol. 146. - No. 5 - P 627-629). The compositions of the prototype were used as controls.

As a method for preclinical studies of the hepatoprotective action of the proposed solution, as in the prototype, the method of liver damage with carbon tetrachloride ["Guidelines for the experimental (preclinical) study of new pharmacological substances" under the general editorship of R.U. Khabrieva, M, 2005]. The inventive biologically active additive was administered at 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. The mice were then euthanized under ether anesthesia and a morphological study of the liver was performed after histological sections were stained with hematoxylin/eosin. In the morphological study of histological sections, the volumetric density of destructive changes (necrosis) in the liver (in %) and the numerical density of binuclear hepatocytes (indicator of regeneration) (in %) were evaluated morphometrically. The compositions of the prototype were used as controls.

As can be seen from Table 1, all compositions of the claimed biologically active additive, both containing as an active component only dextranal, obtained by mechanical activation of dextran, and containing, in addition to it, also extracts of plant materials, have a higher hepatoprotective and immunostimulating activity than the compositions prototype, which proves the great efficiency of the proposed biologically active additives.

The use of the claimed technical solution makes it possible to obtain a dosed preparation that meets the status of biologically active additives, consisting of a minimum amount of highly effective components with a maximum retention of active substances, with increased hepatoprotective and immunostimulating properties.

Claims (5)

1. A composition with hepatoprotective and immunostimulating properties, containing a modified dextran and a physiologically acceptable filler, characterized in that dextranal with a molecular weight of 20-75 kDa, obtained by mechanoactivation of dextran, is used as a modified dextran, with the following content of components, % wt.: dextranal 0.5-10.0 Physiologically acceptable filler up to 100 2. The composition according to claim 1, characterized in that, as a physiologically acceptable filler, it contains dry or aqueous extracts of plant materials selected from the group: a combination of extracts of milk thistle, burdock root and immortelle or a combination of extracts of rose hips and burdock root, microcrystalline cellulose or their mixtures. 3. Composition according to claim 1, characterized in that the physiologically acceptable filler is a liquid, emulsion, suspension, paste. 4. Composition according to claim 3, characterized in that water, saline or buffer solution is selected as the liquid.