RU2436586C1 - St john's wort composition containing compounds of dianthrone series, and method for preparing it - Google Patents

Abstract

FIELD: medicine, pharmaceutics. ^ SUBSTANCE: invention refers to pharmaceutical industry, specifically to a St. John's wort composition. The St. John's wort composition containing compounds of dianthrone series, comprising dried common St. John's wort herb, an abrasive material, an antioxidant preservative, and a salt-forming agent taken in the certain amount and mechanochemically processed. A method for preparing the St. John's wort composition by mixing dried common St. John's wort herb, the abrasive material, the antioxidant preservative and the salt-forming agent in certain proportions, processing mechanochemically in an activator mill. ^ EFFECT: composition contains the increased amount of water-soluble compounds of hypericin and pseudohypericin. ^ 3 cl, 8 tbl, 7 ex

Description

The invention relates to compositions based on St. John's wort, including compounds of the diantrone series, and methods for their preparation. The inventive method allows to obtain a composition of dry grass of St. John's wort, which can be used in medicine and veterinary medicine, cosmetics and feed production and the food industry.

It is known that Hypericum perforatum (Hypericum perforatum L., family Hypericum - Hypericaceae) is part of the pharmacopoeia of our country, some European countries, and on its basis receive drugs with diverse biological activity. For example, antioxidant, antibiotic, antiviral, antistress and antidepressant activities are noted. The mentioned types of activity of these drugs, in particular, are associated with flavonoids, with the sum of the compounds of the diantrone series (anthracene derivatives): hypericin, pseudohypericin, protohypericin, protopsevidogipericin, as well as hyperforin, an antibiotic isolated from St. John's wort (1. Their plant resources, USSR Chemical: Flower composition, use; Families Paeoniaceae - Thymelaeaceae. - L .: Nauka, 1985. - P.16-18).

It should be noted that the compounds of the diantrone series are hardly extracted in water due to the low solubility, therefore, organic solvents have to be used to obtain their extracts.

The well-known "Method of gentle extraction of extract fractions from St. John's wort, pharmaceutical preparations containing them, and their use" (2. US Patent No. 6238671, 2001, С07С 45/78; С07С 46/00; С07С 45/00; А61К 035 / 78; A61K 031/05; A01N 031/08), in which a composition containing the compounds of the diantrone series is obtained from a herbaceous plant Hypericum perforatum L. This method involves preparing an aqueous-alcoholic extract of Hypericum perforatum L., concentrating the extract to a predetermined degree by evaporation to form a precipitate and a supernatant, separating the precipitate from the supernatant, repeating the concentration and separation steps for at least the supernatant, additional re-dissolving the separated sediment obtained at an earlier stage, and obtaining a product - extract of Hypericum perforatum L. - either from the supernatant, or from the precipitate - or from the stage of the formation of sediment and supernatant, or from the stage of re-dissolution.

The disadvantages of the known technical solutions are the use of large volumes of solvents that are explosive, volatile, harmful substances, as well as the oxidation of the target product in the process of extraction, concentration and storage.

Known composition and method for its preparation "Stable extract of Hypericum perforatum L., the method of its manufacture and use as a topical drug" (3. US Patent No. 7166310, 2007, A61K 36/38; A61K 33/04), in which from a herbaceous plant Hypericum perforatum L. a composition is obtained containing compounds of the diantrone series, which includes a stabilizer (an additional antioxidant preservative). This method involves extracting the dried feed obtained from Hypericum perforatum L. with acetone, an aqueous solution of acetone, ethanol, an aqueous solution of ethanol or a mixture of solvents containing acetone and ethanol to form a crude extract, removing chlorophyll and proanthocyanidins from it by filtration using an adsorbent, adding a stabilizer (an additional antioxidant preservative) to the extract.

The disadvantages of the known technical solutions are the use of large volumes of solvents, which are explosive, volatile, harmful substances, as well as the oxidation of the target product in the process of extraction, since the stabilizer (antioxidant preservative) is added after the extraction.

The known composition "Dry extracts from medicinal plants" (4. US Patent No. 6472439, 2002, A61K 9/14; A61K 9/00; A61K 047/32; A61K 009/48; A61K 009/20; A61K 009/46 ; A61K 009/50), which is a dry composition obtained from a herbaceous plant Hypericum perforatum L. and containing compounds of the diantrone series. This composition is a dry extract of a St. John's wort medicinal plant, containing a plant extract, a first carrier and a second carrier, in which the non-volatile phase is bound in a microdispersed form, in the form of a semi-solid or solid composition, or a combination thereof with the first carrier, where the first carrier is polyethylene glycol (e.g. with a molecular weight of 4000), polyvinyl alcohol, polyvidone acetate, polyvinylpyrrolidone, or a combination thereof, optionally having auxiliary substances and additives. This composition may contain a second carrier that is insoluble in alcohol, in water (or swells in water) and is solid at room temperature. A method of preparing this composition includes preparing a liquid St. John's wort extract, adding carriers to this extract (optionally at elevated temperature), concentrating the resulting intermediate to dryness (i.e. drying) to form a semi-solid or solid product. St. John's wort is extracted with organic solvents, their mixtures with each other and with water. As organic solvents, acetone, chloroform, ethyl acetate and C1 ÷ C4 alcohols are used. The extraction is carried out by known methods at room temperature or at elevated temperature. In addition, supercritical carbon dioxide extraction can be used.

The disadvantages of the known technical solutions are the complexity and multi-stage manufacturing of the composition, the use of large volumes of solvents that are explosive, volatile, harmful substances, as well as the oxidation of the target product in the process of extraction, concentration (drying).

The closest technical solution selected for the prototype is a composition based on St. John's wort, consisting of plant materials, including perforated St. John's wort grass and zeolite (abrasive material), processed mechanochemically (5. Pat. RF No. 2320317, publ. 10.10.2007) The disadvantage of this technical solution is the insufficiently high content of water-soluble compounds of the diantrone series in the resulting composition.

The problem solved by the claimed technical solution is to obtain a composition based on the dried herb of St. John's wort of the claimed composition having a high content of water-soluble compounds of the diantrone series (hypericin and pseudo-hypericin).

The problem is solved by the claimed composition of the composition based on St. John's wort, including compounds of the diantrone series, and the method for its preparation.

The problem is solved due to the claimed composition of the composition based on St. John's wort, including compounds of the diantrone series, containing dried Hypericum perforatum grass, abrasive material and, additionally, an antioxidant preservative and a salt-forming agent treated mechanochemically, with the following ratio of components: 1 ÷ 20% salt-forming agent, 1 ÷ 15% abrasive material, 0.5 ÷ 10% preservative antioxidant, dried grass of St. John's wort perforated - the rest, as a salt-forming agent, the composition is soda INH hydroxide, carbonate or hydrogen carbonate of alkali or alkaline earth metals as well as an antioxidant, a preservative - sodium ascorbate.

The problem is also solved due to the fact that in the inventive method for producing a composition based on St. John's wort, comprising mixing dried St. John's wort with abrasive material and mechanochemical processing, a salt-forming agent and an antioxidant preservative are additionally introduced into the mixing process, the resulting mixture comprising a salt-forming agent, abrasive material , antioxidant preservative and dried St. John's wort grass in the following ratio of components (65 ÷ 97.5) :( 1 ÷ 20) :( 1 ÷ 15) :( 0.5 ÷ 10) by weight, respectively, subjected to mechanochemical treatment in a mill-activator, using alkali or alkaline earth metal hydroxide, carbonate or bicarbonate as a salt-forming agent, silica sand or zeolite as abrasive material, and sodium ascorbate as a preservative antioxidant.

Preferably, flow ball vibrocentrifugal, ellipse centrifugal and roller centrifugal mills are used as an activator mill, providing an acceleration of the impacting bodies of 80 ÷ 250 m / s ² and a residence time of the treated mixture in the treatment zone of 0.5 ÷ 2.5 min.

Hypericum perforatum L. perforatum is used as a source of St. John's wort grass, which does not exclude the possibility of using other species of plants of the genus Hypericum L. Moreover, dried ground St. John's wort grass must meet the requirements of GOST 15161-93 and have a moisture content of not more than 13 wt.% (6. GOST 15161-93. "St. John's wort grass. Technical conditions").

The indicated ratios of the concentrations of the components of the mechanochemically processed mixture and the parameters of the mechanochemical processing (acceleration of grinding media, residence time of the processed mixture in the zone of influence of grinding media, the number and geometric characteristics of grinding media loaded into the mechanochemical activator) are determined by the kinetic characteristics of the mechanochemical process.

The use of salt-forming agents provides the transition of diantrons to a water-soluble form directly in the air-dry target product or increases the speed and completeness of the transition of diantrons to a water-soluble form when water is added, for example, when the product powder enters the stomach. The introduction of a salt-forming agent in a concentration of less than 1 wt.% Gives a weak effect, i.e. most diantronic compounds remain in a water-insoluble form. The use of a salt-forming agent in a concentration of more than 20 wt.% Does not lead to an increase in the amount of diantronic compounds in the composition, while its cost increases.

The use of abrasive material increases the grinding efficiency of plant materials and leads to the destruction of cell walls, which in turn allows the extraction of substances located inside the cells and previously inaccessible with water. The use of abrasive material, for example quartz sand, in a concentration of less than 1 wt.% Leads to a decrease in the destruction efficiency of plant raw material cells and a sharp increase in the time of mechanochemical treatment to technologically unacceptable values. The use of abrasive material, for example quartz sand, in a concentration of more than 15 wt.% Is impractical due to the fact that higher concentrations do not increase the efficiency of destruction of cell walls, and the energy consumption for grinding abrasive material increases.

The use of a preservative antioxidant slows down the rate of oxidative degradation of diantrons both in an air-dry composition and in a composition with an added solvent, water. The use of a preservative antioxidant, for example sodium ascorbate, in a concentration of less than 0.5 wt.% Does not produce a noticeable effect. The use of an antioxidant preservative, for example sodium ascorbate, in a concentration of more than 10 wt.% Does not give a further significant increase in the effect, but leads to a decrease in the number of diantrons in the composition.

The inventive method is as follows.

Example 1

Dried crushed grass of a perennial herbaceous hypericum perforated (5) is crushed to a particle size of less than 500 microns. The extraction is carried out in accordance with the information from the patent for the invention, taken as a prototype (5). This composition is used for model laboratory experiments, including experiments on testing the stability of soluble diantrons to oxidative degradation. The analysis of the composition is carried out by HPLC on a MILICHROM A-02 instrument with a UV detector according to a procedure similar to that described in the source (7. Li W., Fitzloff JF High performance liquid chromatographic analysys of St. John's Wort with photodiode array detection // J. Chrom . B: Biomed. Sci. Appl. - 2001. - V.765. - No. 1. - P.99-105), according to which they act as follows. The resulting extract was diluted 3 times with acetonitrile and centrifuged at 8000 rpm for 15 minutes. The supernatant was analyzed by HPLC, an EcoNova column 2 mm × 75 mm with a ProntoSIL 120-5C18AQ sorbent with a particle size of 5 μm. The mixture of eluents is fed in a gradient mode. Eluent A: CH ₃ CN — 38.5%, CH ₃ OH — 16.5%, 0.6% H ₃ PO ₄ in H ₂ O — 45%. Eluent B: CH ₃ CN — 69.7%, CH ₃ OH — 29.7%, H ₃ PO ₄ — 0.6%. The amount of eluent B corresponds to 40-100-100% to a volume of 0-2200-3100 μl at a flow rate of 200 μl / min. The chromatogram has four main peaks. As shown by mass spectrometry, the compounds corresponding to these peaks are identified as protopsevidogipericin, pseudohypericin, protogipericin and hypericin.

Example 2. The effect of mechanochemical processing.

Dried crushed grass of a perennial herbaceous hypericum perforated (5) is crushed to a particle size of less than 500 microns. The resulting intermediate is mixed with sodium carbonate to a homogeneous composition in a ratio of 95: 5 by weight. The mixture is treated in a PM-1 rotary mill-activator (Institute of Chemical Technology and Technology of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk) with an acceleration of the impacting bodies of 200 m / s ² and a residence time of 2 minutes in the treatment zone. The product is a finely divided air-dry powder. The target product contains compounds of the diantrone series from St. John's wort grass and can be used in medicine and veterinary medicine, cosmetics and feed production, and the food industry.

The analysis of the obtained water-soluble compounds of the diantrone series in the target product is carried out as follows: bidistilled water is added to the hydraulic module 10, extraction is carried out for 3 hours at room temperature, the obtained sample is prepared and analyzed by HPLC on a MILICHROM A-02 instrument according to the procedure specified in Example 1. On the chromatogram there are four main peaks. As shown by mass spectrometry, the compounds corresponding to these peaks are identified as water-soluble compounds of protopsevdipericin, pseudohypericin, protohypericin and hypericin. Of the four types of compounds, the concentrations of hypericin and pseudohypericin are analyzed and the concentrations of pseudohypericin and protopsevidogipericin are not analyzed, so the last two compounds are highly unstable and turn into hypericin and pseudohypericin under the influence of light (8. Dewick, PMMedicinal natural products: a biosynthetic approach 3rd ed. // Chichester: John Wiley & Sons Ltd. - 2009 .-- P.108-109). The concentration of water-soluble compounds of diantrons is expressed in relative units (OE), directly proportional to the areas of the chromatographic peaks of these compounds, and refer to 1 g of dried St. John's wort grass (OE / g).

The data obtained are presented in table 1. From table 1 it follows that, as a result of mechanochemical treatment, the yield of extractive water-soluble compounds of hypericin increases by 4 times, and water-soluble compounds of pseudo-hypericin - by 1.7 times. The completeness of water-alcohol extraction of these compounds does not change significantly.

Table 1 Dependence of the completeness of extraction of compounds of hypericin and pseudohypericin on treatment, including mechanochemical treatment in the presence of a salt-forming agent - sodium carbonate Treatment Extraction solvent The relative concentration of soluble compounds, OE / g Hypericin Compounds Pseudohypericin Compounds Grinding Hypericum grass to a particle size of less than 500 microns 85% - ethanol, 15% - water 143 ± 18 138 ± 19 Water 10.1 ± 2.0 39.0 ± 5.5 Mechanochemical 85% - ethanol, 15% - water 142 ± 8 105 ± 7 Water 41.2 ± 5.3 68.3 ± 6.1

Example 3. The effect of abrasive material.

Dried crushed grass of a perennial herbaceous plant Hypericum perforatum (5) is crushed to particle sizes less than 500 microns. The resulting intermediate is mixed with sodium bicarbonate and quartz sand to a homogeneous composition in a ratio of 86: 4: 10 by weight. The mixture is processed in a periodic laboratory mill-activator of the planetary type Pulverisette 5 (manufacturer - Fritsch, Germany) with an acceleration of the acting bodies of 180 m / s ² and a residence time of 2.5 minutes in the treatment zone. The product is a finely divided air-dry powder. The target product can be used for laboratory research.

The analysis of water-soluble compounds of the diantrone series in the target product and the processing of the data obtained is carried out analogously to example 2. The data are presented in table 2. From table 2 it follows that as a result of mechanochemical treatment in the presence of abrasive material, the yield of water-soluble compounds of hypericin increases by 5.6 times, pseudohypericin - 1.9 times. The completeness of water-alcohol extraction of these compounds does not change significantly.

table 2 Dependence of the completeness of extraction of compounds of hypericin and pseudohypericin on treatment, including mechanochemical treatment in the presence of abrasive material (silica sand) Treatment Extraction solvent The relative concentration of soluble compounds, OE / g Hypericin Compounds Pseudohypericin Compounds Grinding Hypericum grass to a particle size of less than 500 microns 85% - ethanol, 15% - water 143 ± 18 138 ± 19 Water 10.1 ± 2.0 39.0 ± 5.5 Mechanochemical 85% - ethanol, 15% - water 145 ± 9 102 ± 11 Water 56.3 ± 4.1 73.2 ± 8.0

Example 4. The influence of salt-forming agent in the presence of abrasive material.

Dried crushed grass of a perennial herbaceous plant Hypericum perforatum (5) is crushed to particle sizes less than 500 microns. The resulting intermediate is mixed with sodium hydroxide and quartz sand to a uniform composition in a ratio of 86: 4: 10 by weight. The mixture is processed in a mill-activator of a centrifugal ellipse type CEM (ICTTM SB RAS, Novosibirsk) with an acceleration of the impacting bodies of 80 m / s ² and a residence time of 2.5 minutes in the treatment zone. The product is a finely divided air-dry powder. The target product contains compounds of the diantrone series from St. John's wort grass and can be used in medicine and veterinary medicine, cosmetics and feed production, and the food industry.

The analysis of water-soluble compounds of the diantrone series in the target product and the processing of the obtained data is carried out analogously to example 2. The data are presented in table 3. From table 3 it follows that as a result of mechanochemical treatment in the presence of an abrasive material and a salt-forming agent, the yield of water-soluble compounds of hypericin increases by 7.7 times pseudohypericin - 2.5 times. The completeness of water-alcohol extraction of these compounds does not change significantly.

Table 3 Dependence of the completeness of extraction of compounds of hypericin and pseudohypericin on treatment, including mechanochemical treatment in the presence of abrasive (silica sand) and salt-forming agent (sodium hydroxide) Treatment Extraction solvent The relative concentration of soluble compounds, OE / g Hypericin Compounds Pseudohypericin Compounds Grinding Hypericum grass to a particle size of less than 500 microns 85% - ethanol, 15% - water 143 ± 18 138 ± 19 Water 10.1 ± 2.0 39.0 ± 5.5 Mechanochemical 85% - ethanol, 15% - water 145 ± 9 102 ± 11 Water 78 ± 6 98 ± 7

Example 5. The effect of additional antioxidant preservative on the completeness of extraction of diantronic compounds.

Dried crushed grass of a perennial herbaceous plant Hypericum perforatum (5) is crushed to particle sizes less than 500 microns. The resulting intermediate is mixed with sodium hydroxide, quartz sand and ascorbic acid to a homogeneous composition in a ratio of 79: 6: 10: 5 by weight. The mixture is processed in a mill-activator of a centrifugal ellipse type CEM (ICTTM SB RAS, Novosibirsk) with an acceleration of the acting bodies of 250 m / s ² and a residence time of 0.5 min in the treatment zone. The product is a finely divided air-dry powder. The target product contains compounds of the diantrone series from St. John's wort grass and can be used in medicine and veterinary medicine, cosmetics and feed production, and the food industry.

The analysis of water-soluble compounds of the diantrone series in the target product and the processing of the obtained data is carried out analogously to example 2. The data are presented in table 4. From table 4 it follows that as a result of mechanochemical treatment in the presence of abrasive material, a salt-forming agent and an additional antioxidant preservative, the completeness of water and water alcohol extraction of diantrons (compared with the results from example 4) does not change significantly, i.e. the use of an additional antioxidant preservative in the indicated concentration practically does not worsen the mentioned indicators.

Table 4 Dependence of the completeness of extraction of hypericin and pseudo-hypericin compounds on treatment, including mechanochemical treatment in the presence of an additional antioxidant preservative Treatment Extraction solvent The relative concentration of soluble compounds, OE / g Hypericin Compounds Pseudogipericin Compounds Grinding Hypericum grass to a particle size of less than 500 microns 85% - ethanol, 15% - water 145 ± 9 102 ± 11 Water 78 ± 6 98 ± 7 Mechanochemical 85% - ethanol, 15% - water 140 ± 5 107 ± 13 Water 80 ± 8 101 ± 5

Example 6. The stability of soluble diantrons to oxidative degradation during storage of air-dried samples under normal conditions with natural light and air access.

The freshly prepared extract of example 1 is dried in a rotary evaporator at room temperature. The resulting product is a black crystals. The product is tested for storage under normal conditions under natural light and air, after which it is diluted with acetone to its original volume, prepared and analyzed according to the procedure described in Example 1. For these experiments, acetone was selected as a model organic solvent, due to that diantrons dissolve well in it and it is often used in known methods for producing an extract of diantrons.

Samples of the freshly prepared composition according to examples 3, 4, 5 are tested for storage under normal conditions under natural light and air, after which they are prepared and analyzed according to the procedure described in example 2, with the difference: the samples are extracted at room temperature for 2 hours .

The relative concentration of soluble hypericin compounds, relative units (OE),%, refers to the chromatographic peak area of soluble hypericin compounds, expressed as% of the initial value of this value in the case of the sample at the initial moment of storage time.

The relative concentration of the sum of soluble diantrons, relative units (OE),%, refers to the total area of the chromatographic peaks of the soluble compounds of protopseudohypericin, pseudohypericin, protohypericin and hypericin, expressed in% of the initial value of this value in the case of the sample at the initial moment of storage time.

The results are presented in tables 5, 6. From tables 5, 6 it follows that the introduction of an additional antioxidant preservative significantly slows down the rate of oxidative degradation of diantrons when storing samples of the composition in an air-dry state.

Table 5 Resistance of soluble hypericin compounds to oxidative degradation during storage of air-dried samples under normal conditions under natural light and air access Samples according to example No. The relative concentration of soluble compounds of hypericin, OE,%, after storage 0 month 3 month 6 months 18 months one one hundred 101.3 ± 5.3 100.2 ± 6.7 82.1 ± 6.2 3 one hundred 98.3 ± 7.2% 95.4 ± 6.8% 88.2 ± 7.1% four one hundred 97.4 ± 6.9% 96.3 ± 5.9% 89.1 ± 4.3% 5 one hundred 102.1 ± 7.6% 99.5 ± 8.1% 97.4 ± 6.3%

Table 6 Resistance of the sum of soluble diantrons to oxidative degradation during storage of air-dried samples under normal conditions under natural light and air access Samples according to example No. The relative concentration of the sum of soluble diantrons, OE,%, after storage 0 month 3 month 6 months 18 months one one hundred 97.3 ± 4.8 102.2 ± 7.6 84.2 ± 5.3 3 one hundred 97.5 ± 6.8% 98.2 ± 4.9% 79.8 ± 6.8% four one hundred 95.9 ± 7.1% 97.3 ± 8.1% 84.3 ± 6.2% 5 one hundred 104.8 ± 8.1% 101.2 ± 5.7% 99.8 ± 5.6%

Example 7. The stability of soluble diantrons to oxidative degradation during storage of samples in liquid form.

The freshly prepared extract of example 1 is dried in a rotary evaporator at room temperature. The resulting product is diluted with acetone to the original volume. For these experiments, acetone was chosen as a model organic solvent, due to the fact that diantrons dissolve well in it and it is used in known methods for producing diantrone extract. The resulting solution was tested for storage under normal conditions under natural light and air, after which it was prepared and analyzed according to the procedure described in example 1.

From freshly prepared samples of the composition according to examples 3, 4, 5, extracts are prepared for two hours at room temperature in bidistilled water at a water ratio of 1: 10 by weight and subjected to storage testing under normal conditions under natural light and air, after which they are analyzed according to the procedure described in example 2.

The results are presented in tables 7, 8. Under the relative concentration of soluble hypericin compounds, as well as the sum of soluble diantrons, relative units (OE),%, we mean the same as in example 6. From tables 7, 8 it follows that soluble diantrone compounds in model organic solvent (acetone) are noticeably subjected to oxidative degradation over a time of the order of hours. This is a disadvantage of the known methods for the preparation of products containing diantrons, where organic solvents are used (and where the time of the corresponding technological procedures is of the order of hours). From tables 7, 8 it follows that the introduction of an additional antioxidant preservative significantly slows down the rate of oxidative degradation of diantrons when storing samples of the composition in liquid form, and therefore, when extracted with water.

Table 7 Resistance of soluble hypericin compounds to oxidative degradation during storage of samples in liquid form Samples according to example No. Solvent The relative concentration of soluble compounds of hypericin, OE,%, after storage 0 hours 8 ocloc'k 16 hours 24 hours one acetone one hundred 62.0 ± 3.0 25.2 ± 1.5 11.6 ± 1.1 3 water one hundred 51.0 ± 3.1 24.4 ± 1.8 12.1 ± 1.5 four water one hundred 52.0 ± 3.4 22.2 ± 1.8 11.8 ± 1.3 5 water one hundred 84.0 ± 5.2 71.3 ± 5.5 52.6 ± 3.1

Table 8 Resistance of the sum of soluble diantrons to oxidative degradation during storage of samples in liquid form Samples according to example No. Solvent The relative concentration of the sum of soluble diantrons, OE,%, after storage 0 hours 8 ocloc'k 16 hours 24 hours one acetone one hundred 72.3 ± 5.4 55.3 ± 3.1 38.7 ± 2.5 3 water one hundred 62.3 ± 5.0 45.7 ± 2.9 31.6 ± 2.7 four water one hundred 64.1 ± 5.5 47.3 ± 3.0 30.7 ± 2.4 5 water one hundred 82.3 ± 6.4 69.3 ± 5.1 45.2 ± 3.5

Using the invention will allow using a new, technologically simple method to obtain a composition containing an increased amount of water-soluble compounds of the diantrone series from the St. John's wort perforated. Compared with the prototype in the claimed technical solution, the composition has a composition different from the prototype, mechanochemical activation is carried out in activator mills under the claimed modes, which allows for more complete conversion of the compounds of the diantrone series of St. John's wort perforated into a water-soluble form.

An additional positive effect achieved by the invention is the possibility of using the latter in medicine and veterinary medicine, cosmetics and fodder production, the food industry to obtain compositions (which are or are part of medicinal and veterinary preparations, cosmetics, animal feed, feed additives and feed additives, biologically active additives to food) containing compounds of the diantrone series from St. John's wort grass.

Bibliography

1. Plant resources of the USSR: Flowering plants, their chemical composition, use; Families Paeoniaceae - Thymelaeaceae. - L .: Nauka, 1985 .-- P.16-18.

2. Joseph H.W. Process for the gentle recovery of extract fractions from hypericum, pharmaceutical preparations containing the same and their use. U.S. Patent No. 6,238,671, 2001, C07C 45/78; С07С 46/00; С07С 45/00; A61K 035/78; A61K 031/05; A01N 031/08.

3. Koch E., Erdelmeier C., Herrmann J. Stable extract from Hypericum perforatum L., method for the production thereof and its use as a topical medicament. US patent No. 7166310, 2007, A61K 36/38; A61K 33/04.

4. Schierstedt D. Medicinal plant dry extracts. US patent No. 6427439, 2002, AK61K 9/14; A61K 9/00; A61K 047/32; A61K 009/48; A61K 009/20; A61K 009/46; A61K 009/50.

5. Pat. RF №2320317, publ. 10/10/2007

6. GOST 15161-93. “St. John's wort grass. Technical conditions. "

7. Li W., Fitzloff J.F. High performance liquid chromatographic analysys of St. John's Wort with photodiode array detection // J.Chrom. B: Biomed. Sci. Appl. - 2001. - V.765. - No. 1. - P. 99-105.

8. Dewick, P. M. Medicinal natural products: a biosynthetic approach. 3rd ed. // Chichester: John Wiley & Sons Ltd. - 2009. - P.108-109.

Claims (3)

1. Composition based on St. John's wort, including compounds of the diantrone series, containing dried Hypericum perforatum and abrasive material processed mechanochemically, characterized in that it additionally contains an antioxidant preservative and a salt-forming agent and has the following composition, wt.%:
salt forming agent 1-20 abrasive material 1-15 antioxidant preservative 0.5-10 dried herb hypericum perforatum rest
moreover, as a salt-forming agent, the composition contains alkali metal or alkaline earth metal hydroxide, carbonate or hydrogen carbonate, contains silica sand or zeolite as an abrasive material, and sodium ascorbate as a preservative antioxidant. 2. The method of obtaining a composition based on St. John's wort, including compounds of the diantrone series, by mixing the dried St. John's wort grass perforated with abrasive material and mechanochemical treatment, characterized in that during the mixing process a salt-forming agent and an antioxidant preservative are additionally introduced, the resulting mixture comprising dried St. John's wort perforated, salt-forming agent, abrasive material and antioxidant preservative, taken in the ratio (65-97.5) :( 1-20) :( 1-15) :( 0.5-10) by weight, respectively, subjected to mechanical chemical treatment in an activator mill, using alkali or alkaline earth metal hydroxide, carbonate or bicarbonate as a salt-forming agent, silica sand or zeolite as abrasive material, and sodium ascorbate as a preservative antioxidant. 3. The method according to claim 2, characterized in that as a mill-activator use flowing ball vibrocentrifugal, ellipse centrifugal and roller centrifugal mills, providing acceleration of the impacting bodies of 80-250 m / s ² and a residence time of 0.5- 2.5 minutes