RU2254032C2 - Composition of bioactive compounds - Google Patents

Abstract

FIELD: food processing industry, in particular production of composition from vegetable raw materials.

SUBSTANCE: claimed composition represents mixture of 71-78 mass % of betuline, 3-10 mass % of betulinic acid and 12-26 mass % of joint products obtained from birch bark. Composition of present invention makes it possible to provide enzyme and energy regulation of innercell homeostasis and cell membrane stabilization.

EFFECT: increased human cell resistance against hostile environment.

2 tbl, 6 ex

Description

The invention relates to the food industry, in particular to the production of a composition made from plant materials and used as a food additive both independently in the form of capsules, tablets, dragee boluses, lozenges, etc., and in food products: cereals, chocolate, sweets, dairy products, bakery products, canned goods, meat products, drinks, etc. (the content in the finished product is from 0.0001% to 50%).

The composition of biologically active substances can also be used in the cosmetic industry as a part of creams, toothpaste, shampoos, lotions, tonics, hair spray, nail polish, etc. (content in the finished product is from 0.001 to 50%).

In addition, the composition of biologically active substances can be used for the manufacture of various dosage forms for internal, external and parenteral use (tablets, capsules, solutions, suppositories, aerosols, ointments, etc.).

The use of new, harmless dietary supplements allows you to expand the range and increase the biological value of food products, give them a certain focus, as well as change the structure of food consumption by the population in accordance with the well-known theories of balanced and adequate nutrition. Biologically active food supplements underlie the creation of specialized (functional) food products intended for dietary correction of pathological conditions and diseases.

Dietary supplements, accumulating a small amount of high biological activity, are able to influence the deep metabolic processes in the body, activating the functions of various organs and systems. Low energy value with high biological activity makes these supplements especially important for patients with obesity, where the use of many nutrients is limited by the level of their energy capacity.

A known composition of biologically active substances, used as a dietary supplement, containing finely divided leaves of Fraxinus excelsior as an active ingredient, and intended to stimulate the glandular function of the body (French patent No. 2590171, class A 23 L 1/30, 1996).

A known method for the separation of betulinol (betulin), with which a mixture of three main components is obtained: betulinol 60-70%, lupeol and betulinic acid methyl ester (patent RU No. 2206572, class C 07 J 53/00, C 07 J 63 / 00, published on June 20, 2003).

The closest in technical essence and the achieved result is a method for producing betulin, according to which a mixture can be obtained, including betulin, betulinic acid and related substances (patent CA No. 2381967, class C 07 J 63/00, 2001 Prototype).

The known mixture includes components in the following proportions, wt.%:

betulin 61 betulinic acid 2 related substances 37

or

betulin 80 betulinic acid thirteen related substances 7

The known mixture with the given ratios of the components has known specific properties inherent in the two main components - betulin and betulinic acid.

The disadvantages of the known mixture are: the impossibility of industrial production of the mixture with the specified specific ratios (within one percent) of the components included in it due to the inability to standardize the source of plant materials (birch bark) on an industrial scale. The content of the above components in the feedstock (birch bark), and therefore in the extract, depends on factors such as the type of birch, its place of growth, age, and the seasonal time of birch bark harvesting.

The technical result, which this technical solution is aimed at, is to obtain a composition of biologically active substances in which the corresponding ratio of basic and related substances provides both synergistic potentiation of known biological activity and a number of new biological effects, such as enzymatic-energy regulation of intracellular homeostasis stabilization of cell membranes due to the regulation (including allosteric) of the activity of enzymatic systems m and the permeability of cell membranes, which helps to increase the resistance of cells of the human body to adverse effects, improve their functioning and increase the time of their active life, potentiate the effects of certain drugs (enzymatic, antibiotics, cytostatics, hormonal, anti-allergic, anti-inflammatory, etc.) and reduce their negative side effects.

In addition, the proposed composition of biologically active substances, in comparison with known analogues, has a number of new biological effects of a central level, namely: anti-allergic, immunomodulating and thermoregulating, stimulation of working capacity, memory, normalization of sleep and regulation of body weight.

The specified technical result is achieved by the fact that in the composition of biologically active substances, including a mixture of betulin, betulinic acid and related substances obtained by extraction from birch bark, according to the invention, the components of the mixture are selected in the following ratio, wt.%:

betulin 71-78 betulinic acid 3-10 related substances 12-26

The composition of biologically active substances according to the invention can be obtained by extraction of only the outer layer of birch bark - birch bark.

In the composition of biologically active substances, the concomitant substance is lupeol.

In the composition of biologically active substances, the concomitant substance is uveol.

In the composition of biologically active substances, the concomitant substance is betulin acetate.

In the composition of biologically active substances, the concomitant is oleanolic acid.

In the composition of biologically active substances, the concomitant substance is a mixture of lupeol, uveol, oleanolic acid and betulin acetate.

The use of biologically active substances in the composition as a concomitant substance (12-26 wt.%) Of lupeol can enhance the antilithogenic effect of betulin and betulinic acid.

The use of biologically active substances in the composition as a concomitant substance (12-26 wt.%) Uveol can enhance the antitumor effect of betulin and betulinic acid.

The use of biologically active substances in the composition as a concomitant substance (12-26 wt.%) Oleanolic acid can enhance the antiviral effect of betulin and betulinic acid.

The use of biologically active substances in the composition as a concomitant substance (12-26 wt.%) Betulin acetate can enhance the hepatoprotective effect of betulin and betulinic acid.

The introduction of biologically active substances into the composition, in addition to betulin and betulinic acid, as accompanying substances (12-26 wt.%) Of lupeol, uveol, betulin acetate, oleanolic acid or a mixture thereof allows to obtain a new biological effect, expressed in the synergistic potentiation of the biological activity of betulin and betulin acids without increasing the toxicity of the mixture to the body.

The use of accompanying substances in the composition of biologically active substances in the range of 19-26 wt.% With a percentage ratio of the components: lupeol (90%), uveol (5%) and oleanolic acid (5%) can significantly potentiate the biological activity of betulin and betulinic acid, directed on the enzymatic-energy regulation of intracellular homeostasis, stabilization of the permeability of cell membranes, and to achieve maximum antiviral, anti-inflammatory, anti-rheumatic and antilithogenic effects. This allows you to significantly reduce or increase (relative to the applied) dosage of anti-inflammatory drugs and antibiotics.

The use of biologically active substances in the composition as accompanying substances (12-19 wt.%) With a percentage ratio of the components: lupeol (70%), uveol (15%) and oleanolic acid (15%) allows you to potentiate the biological activity of betulin and betulinic acid, aimed at ensuring maximum stabilization of cell membranes by regulating (including allosteric) activity of enzymatic systems, increasing the resistance of cells of the human body to adverse effects, improving their functional Maintenance time and increasing their active life and also enhances the hepatoprotective, onkoprotektivnoe, hypolipidemic, cardiotonic action and antiallergic composition of the human body. This allows you to significantly reduce the dosage of hormones, cardiotonics and increase the dose of cytostatics and enzyme drugs used to treat a wide range of diseases.

As a raw material for obtaining this composition of biologically active substances in the form of “Birch dry extract” (BES) by extraction with organic solvents, birch bark of the main types of birch growing in Russia is used:

- Betula pendula (drooping), aka B. talassica Poljak., B. verrucosa Ehrh. (warty) and

- Betula pubescens Ehrh. (fluffy) she is also B. alba L. (white).

Known methods for extracting birch bark make it possible to obtain extracts containing a mixture of pentacyclic triterpene compounds: betulin (synonyms: betulenol, betulinol, trachol, birch camphor, lupendiol) as the main substance in the range of 71-78 wt.% In combination with betulinic acid (3- 10 wt.%) And related substances (lupeol, uveol and oleanolic acid) (12-26 wt.%).

Known variants of the biological activity of betulin, betulinic acid and the accompanying accompanying substances are largely similar, but the mechanisms for its implementation are both similar and excellent. Therefore, when combined using them, the effect of synergistic potentiation occurs, which is expressed in a significant increase in the overall biological effectiveness than the use of each substance separately.

The biological activity of the main and related substances of the composition, demonstrating the prospects of its use as a raw material for the production of biologically active food additives, are given in table 1.

The examples of biological activity of extractive substances given in table 1 are realized through various mechanisms of action.

Studies of toxicity and specific activity revealed a combination of pronounced biological activity of the extract and the absence of its toxicity to the body.

It is known that the anti-inflammatory activity of triterpene compounds exceeds that of non-steroidal anti-inflammatory drugs (betulin is 25 times higher than that of indomethacin) (O.A. Rapp. Abstract, Tomsk Scientific Research Institute of Pharmacology, 1993).

It is known that, under the influence of betulin, the content of free triglycerides in the blood is reduced by 53% and the level of cholesterol in the blood is reduced by 25%, in the aortic tissue - by 57%. There is a delay in the absorption of cholesterol from the intestine, increased oxidation to bile acids and excretion with bile (V.F.Semenchenko. Abstract, Pyatigorsk, 1992).

The effectiveness of betulin and its related triterpenes against the influenza virus and some other respiratory viruses, all forms of the herpes virus, is known. Betulinic and oleanolic acids are effective against human immunodeficiency virus (Toshihiro Fujioka, Yoshika Kashiwada et al., Natural Products Laboratory, Department of Medical Chemistry and Natural Products, Faculty of Pharmaceuticals, University of North Carolina. Journal of Natural Products. 1994, T. 57, No. 2, p. 243-247).

Numerous studies show that betulin, partially lupeol, and especially betulinic acid, are effective against Epstein-Barr virus and in such forms of cancer as skin melanoma, neuroblastoma, medulloblastoma, Walker sarcoma, breast adenoma, leukemia, epidermoid carcinoma of the nasopharynx, carcinoma guts and some others.

The hepatoprotective and alcohol protective effects of betulin have been studied in three classic models of hepatitis. On all models, betulin showed the same activity as the official drug silibor, but at a much lower dose of 1 mg / kg (Dyachuk G.I. et al., Proceedings of the I.M. Mechnikov State Medical Academy, St. Petersburg, 2003).

The anti-stress effect of birch extract, gastroprotective effect in acute stomach injuries, reserpine and histamine ulcers, subchronic butadione and acetylsalicylic ulcers, chronic acetate ulcers were studied. Moreover, the birch bark extract not only demonstrated gastroprotective effect at the level of befungin and plantaglucide, but also had a complex effect on the gastric mucosa when it is damaged, due to both the effect on protective factors and the weakening of the acid-peptic potential of gastric juice and a decrease in the level of saline acids. At the same time, the bark bark extract showed an antispasmodic, analgesic and phlogilistic effect. (O.A. Rapp. Abstract, Tomsk Scientific Research Institute of Pharmacology, 1993).

Thus, the proposed composition of biologically active substances can be used as the main component of biologically active food additives, and with the indicated ratio of the components of the mixture of pentacyclic triterpene compounds, the additive can be used as a general strengthening agent, choleretic, gastro-and hepatoprotective, alcohol-protective, antiviral, anti-sclerotic and oncostatic orientation, and will significantly reduce or increase the dosage of drug eparatov used to treat a wide range of diseases.

The inclusion of the composition of biologically active substances in the system of therapeutic and prophylactic nutrition is promising. For example, a dry mixture - porridge as a specialized food product for people suffering from gastrointestinal tract problems (gastritis, peptic ulcer, biliary dyskinesia, hepatitis, cirrhosis), contains 0.5% by weight of birch extract (betulin - 75% , betulinic acid - 3%, related substances - 22%, with the following percentage: lupeol - 80%, uveol - 10%, oleanolic acid - 10%). A product using a composition of biologically active substances is prepared by mixing the dry ingredients. The food composition is a powder with a neutral taste, taste and smell characteristic of the type of raw material used.

In addition, this composition can be used as a biologically active additive (BAA) to food in standard forms for this type of product: capsules, tablets, dragees, boluses, lozenges, tinctures, etc. To prepare the composition, use conditioned raw materials that meet the requirements of the current regulatory and technical documentation. The product is prepared by mixing dry ingredients with or without further wet granulation and encapsulation (or tabletting).

Example 1. The formulation of the dietary supplement "Birch extract dry"

No. p / p Name of substance The amount of substance, mg 1 Dry birch extract twenty 2 Filler (lactose, maltose or otherwise) 180 Total 200 ± 10

The extract contains 78% betulin, 3% betulinic acid and 18% of the accompanying substances with the following percentage of components: 10% oleanolic acid, 10% uveol and 80% lupeol. Supplements are packaged in 200 mg capsules No. 1 or No. 0 or tabletted according to TU 9379-003-54334186-02. Packing in plastic cans or medical foil blisters for 5 - 220 capsules in accordance with TU 9379-003-54334186-02.

Example 2. The formulation of dietary supplements "BETULA-DE-TOX"

No. p / p Name of substance The amount of substance, mg In one capsule In one tablet 1 Dry birch extract twenty twenty 2 Rutin (Vitamin P) fifty fifty 3 Ascorbic Acid (Vitamin C) fifty fifty 4 Filler (lactose, maltose or otherwise) 65 35 TOTAL: 210 ± 10% 180 ± 10%

The chemical composition of the extract is similar to the dietary supplement "Dry birch extract." Supplements are packaged in capsules No. 0 or No. 1 at 210 ± 10% mg or tableted according to TU 9379-004-54334186-02.

Take these dietary supplements for adults 1-2 capsules / tablets 2-3 times a day with meals. Clinical trials of Betula de Tox (BDT) dietary supplements revealed its positive effect on intestinal motor function (normalization and regularity of stool), reduction of discomfort syndrome (disappearance of heartburn and nausea, cessation of pain in the right hypochondrium, disappearance of dyspeptic phenomena) and Improving the general well-being of patients (increasing overall tone, reducing adynamia). Symptoms of intolerance to the drug or allergic reactions were not detected. As a rule, taking 1-2 capsules eliminates the feeling of discomfort in the gallbladder area (in case of dysfunction) within 15 minutes.

Many male patients report increased sexual function while taking dietary supplement data. Persons of the older age group note normalization of sleep without a pronounced sedative effect. Significantly reduced exposure to ARVI and reduced treatment time for colds.

All of these dietary supplements are made in the form of dragees or boluses of 200-500 mg or are capsulated, or tabletted and packaged in plastic cans or medical foil blisters for 2-200 pieces, or in other authorized packaging.

Example 3. The recipe dietary supplement "GASTROBETOL"

No. p / p Name of substance The amount of substance, mg (capsule No. 1) The amount of substance, mg (capsule No. 0) 1 Dry birch extract 26 26 2 Plantain dry extract (plantaglucid) 105 105 3 Aloe vera juice (in terms of dry matter) 6 6 4 Filler (lactose, maltose or otherwise) 123 213 Total 260 + 10% 350

Example 4. The formulation of dietary supplements antistress action

No. p / p Name of substance The amount of substance, mg 1 Dry birch extract 25 2 Dry valerian extract 10 3 Monosodium glutamate 150 4 Filler (lactose, maltose or otherwise) 60 Total 250 + 10

Example 5. The formulation of dietary supplements antirheumatic action

No. p / p Name of substance The amount of substance, mg 1 Dry birch extract 25 2 Bromelain 150 3 Filler (lactose, maltose or otherwise) 75 Total 250 ± 10

Example 6. The formulation of dietary supplements antiviral action

No. p / p Name of substance The amount of substance, mg 1 Dry birch extract 25 2 Ascorbic Acid (Vitamin C) fifty 3 Chlorophyll carotene paste fifty 4 Filler (lactose, maltose or otherwise) 125 Total 250 + 10

This composition of biologically active substances can be used to create cosmetic products. The combination of betulinic acid (5%) and oleanolic acid (1%) as substances with an elastase inhibitory effect, in combination with betulin (75%) as an inhibitor of prostaglandin synthesis, allows to obtain an anti-wrinkle cream with an active ingredient content of 0.5 to 5% by weight.

The use of the antiviral effect of betulin (75%), betulinic acid (5%) and related substances (20%) with the following percentage of components: lupeol - 70%, uveol - 15%, oleanolic acid - 15% allows you to get a cream, gel or ointment for the treatment of inflammatory lesions of the skin and mucous membranes, herpes of any localization (including genital), the prevention and treatment of influenza and other acute respiratory viral infections with active components from 0.5 to 5% by weight.

Mode of application. For the treatment of herpetic lesions of the skin and mucous membranes, apply the ointment to the affected areas 3-5 times a day until complete recovery.

For the treatment of inflammatory lesions of the skin and mucous membranes, apply ointment to the affected areas 2-3 times a day.

In the treatment of influenza and SARS, use the ointment 4-5 times a day.

For the prevention of influenza and SARS during the period of seasonal incidence rises, apply a small amount of ointment to the nasal mucosa 1-2 times a day.

The proposed composition of biologically active substances has been successfully tested at the Institute of Nutrition RAMS and on its basis the Ministry of Health of the Russian Federation registered a number of biologically active food additives.

The tolerance of biologically active food additives and functional foods using the proposed composition was good, their pleasant taste and aroma were noted.

With the course use of the supplement, an increase in the therapeutic effect of the traditionally used types of treatment was noted.

The biological activity of the proposed composition, confirmed as a result of biological research and clinical trials, demonstrated the promise of using the composition as a direct regulator of the activity of enzymatic systems of body protection. The proposed composition allows you to control the number of enzymes in the cell by regulating their synthesis and decay, the effect on the activity of enzymes and their allosteric regulation.

Since when examining the subject of the invention in patent and scientific literature, no solutions were found containing the features of the claimed invention other than the prototype, it should be concluded that the claimed invention meets the criterion of "significant differences".

The use of the claimed invention in the food industry ensures that it meets the criterion of "industrial applicability".

Claims (7)

1. The composition of biologically active substances, including a mixture of betulin, betulinic acid and related substances obtained by extraction from birch bark, characterized in that the components of the mixture are selected in the following ratio, wt.%: betulin 71-78 betulinic acid 3-10 related substances 12-26. 2. The composition of biologically active substances according to claim 1, characterized in that it is obtained by extraction of only the outer layer of the birch bark - birch bark. 3. The composition of biologically active substances according to claim 1, characterized in that the concomitant substance is lupeol. 4. The composition of biologically active substances according to claim 1, characterized in that the concomitant substance is uveol. 5. The composition of biologically active substances according to claim 1, characterized in that the concomitant substance is betulin acetate. 6. The composition of biologically active substances according to claim 1, characterized in that the concomitant substance is oleanolic acid. 7. The composition of biologically active substances according to claim 1, characterized in that the concomitant substance is a mixture of lupeol, uveol, betulin acetate, oleanolic acid.