RU2567035C2 - Echinacea tincture and method for producing echinacea tincture - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, namely to Echinacea herb tincture having immunomodulating, immunopotentiating, antimicrobial, anti-inflammatory, antiviral activity and a method for producing it. The method for producing Echinacea herb tincture consists in extracting ground Echinacea herb in ethanol, infusing, then mixing, infusing more, pouring off a portion of the extract; after pouring off the extract, the process herb is added with fresh extracting agent, infusing while stirring at regular intervals; all the extract is poured off; the prepared extracts are combined and cooled thoroughly, filtered in a certain environment. Using the method for producing the Echinacea herb tincture having immunomodulating, immunopotentiating, antimicrobial, anti-inflammatory and antiviral activity. The Echinacea herb tincture having immunomodulating, immunopotentiating, antimicrobial, anti-inflammatory and antiviral activity.

EFFECT: method enables producing the Echinacea herb tincture with preserving the biological activity of its components, therapeutic effects and benefits, however reducing considerably the ethanol concentration in the end product.

3 cl

Description

State of the art

The invention relates to the pharmaceutical industry, in particular to a tincture of Echinacea herb having immunomodulatory, immunostimulating, antimicrobial, anti-inflammatory and antiviral activity and a method for its preparation. The tincture can be used to increase the protective and immune properties of the body during seasonal diseases for the prevention and treatment of various respiratory infections, flu, colds, recurrent respiratory infections and other similar diseases in adults and children from 3 years of age.

A number of pharmacological preparations based on substances from various species of plants of the genus Echinacea are known, as well as various methods for their preparation.

The genus Echinacea comes from North America. It belongs to the Asteracea family. Echinacea as an immunostimulant has become very popular in recent years, although its healing properties have been known since ancient times. The Indians used it for inflammation, for cough and sore throat, for toothache, diseases of the gastrointestinal tract, burns, and considered it a strong antidote for snake bites. In the language of the Indians, Echinacea means "snake root." At the end of the XVII century. Echinacea was introduced to Europe, where it quickly gained popularity as an ornamental plant of botanical gardens. In the medical literature, the first mention of echinacea as a means of accelerating wound healing in racehorses appeared in 1762.

The chemical composition of the plant:

- Echinacea herb contains polysaccharides, essential oils (0.15-0.50%), flavonoids, phenylpropanoids (chicorye, chlorogenic, caftaric acid), tannins, saponins, polyamines, echinacin, echinolone, echinacoside, organic acids, resins, phytosterols ;

- rhizomes and roots - inulin (up to 5.9%), glucose (7%), essential and fatty oils, phenylpropanoids, betaine, resins.

All parts of the plant contain enzymes, macro- (potassium, calcium) and trace elements (selenium, cobalt, silver, molybdenum, zinc, manganese, etc.).

The pharmacological activity of Echinacea is determined by the following biologically active substances:

- phenylpropanoids and their derivatives: chicorye acid (2,3-O-dicofeilvinnoy acid), caftaric and chlorogenic acids, echinocoside (2,3-O-dicofeylvinnoy acid glucoside), cinarin;

- flavonoids: luteolin, luteolin-7-glucoside, kempferol and its 3-glucoside, and 3-rutinoside, quercetin and its 3-glucoside, 3-xyloside, 3-arabinoside, rutin and others;

- unsaturated carbohydrates (polyines) that are part of the essential oil: echinol, 1-pentadecene, 1.8 Z-pentadecadiene;

- alkylamides of unsaturated acids, in particular echinacein (dodeca-2E, 6Z, 8E, 10E-tetraenoic acid isobutylamide), isobutylamides (dodeca-2E, 4E, 8Z, 10E-tetraenoic and dodeca-2E, 4E, 8Z, 10Z-tetraenoic acid )

All known preparations based on Echinacea have a different concentration of substances extracted from the plant, as well as different quantitative and qualitative composition of the extracted substances and compounds and different concentrations of ethyl alcohol, which is due to the different technology of their industrial preparation, and therefore all known preparations based on Echinacea various qualitative and quantitative composition, various physico-chemical properties.

It is also known that with various cooking technologies, the content and ratio of substances and compounds extracted from plant materials, as well as their pharmacological activity, change (Muravyov I.A. Drug technology. 3rd edition, revised and additional T. 1, 2. - M .: Medicine, 1980).

In Russia, a number of pharmacological preparations are known, obtained on the basis of substances from various species of plants of the genus Echinacea, as well as by various methods of their preparation from various parts of plants: roots, inflorescences, and terrestrial parts:

- Echinacea VILAR® (Echinacea purpurea grass), manufacturer CJSC Pharmacenter VILAR;

- Echinacea-GalenoPharm® (Echinacea purpurea grass), manufacturer of OJSC "Pharmaceutical Factory of St. Petersburg";

- Immunal® plus C (Echinacea herb juice dried) and Immunal® (Echinacea herb juice dried), manufacturer Sandoz DD, Slovenia;

- Dr. Theiss Echinacea tincture (Echinacea angustifolia), Dr. Theiss Echinacea forte (Echinacea purpurea juice juice) and Doctor Theiss Echinacea extract (Echinacea purpurea herb extract), manufacturer Dr. Theiss Naturvaren GmbH, Germany.

The known preparations are Echinacin Liquidum (series 518626, Germany) and Immunal (series BU2491, manufactured on 07.2011, valid until 07.2013, Slovenia), obtained by pressing a freshly picked plant and adding 22 or 20% ethyl alcohol. A technical drawback of such technologies is the possibility of precipitating precipitates in fresh Echinacea juice and the need for this to regulate the acidity of pH below 6 with acid (patent EP 0920871 A1, A61K 35/78, published 09.06.1999).

There is a method of obtaining an immunomodulating drug "Tincture of Echinacea purpurea" using ethyl alcohol, according to which, in order to increase the yield of phenylpropanoids, the echinacea herb is extracted three times with 40% ethyl alcohol by maceration in three extractors with a ratio of raw material: extractant equal to 1: 8 and the first extraction is carried out at room temperature and the next two when heated to 70-80 ° C for 30 minutes (patent RU 2134584, A61K 35/78, publ. 20.08.99). The disadvantage of this method is the use of elevated temperatures at which valuable biologically active substances decompose.

Also known is the tincture of Echinacea Dr. Taiss (series 05/08/13, Austria) and the method for its preparation (Bauer R., Wagner N. Echinacea: Hand-buch fur Artze Apotheker und andere Naturwissenschaftler. - Stuttgart: Wissenschaftliche Verlagschaft. 1990. -182 s. ; patent RU 2134584, A61K 35/78, publ. 08.20.99). The essence of this method lies in the fact that Echinacea grass is poured with extractant (55% ethanol), insisted for 7 days, then the extract is drained, the residue is pressed several times and washed with extractant and squeezed extracts to the required volume. As a result of extraction by the method of maceration, a tincture of Echinacea by Dr. Theiss is obtained with a solids content of 0.4% and a phenylpropanoid content of 0.02%. The technical disadvantages of this tincture and the method for its preparation are the relatively low content of extractive substances (0.4%) and target components, the duration of the process (more than 7 days, the extraction stage), insufficiently high yield of extractive substances and incomplete extraction of plant materials.

A known method of obtaining tincture from Echinacea purpurea, in which 40% ethyl alcohol is used as an extractant, extraction of Echinacea herb is carried out by the method of modified maceration, combining extraction at room temperature and when heated in the temperature range 70-80 ° C (RU 2288732 C1, 12/10/2006). The disadvantages of this method are the incomplete extraction of raw materials and, as a consequence, the low yield of the target substances, as well as the use of high temperature, at which valuable biologically active substances are destroyed.

A well-known document (Gordiychuk G.N. Study of the kinetics of equilibrium when extracting echinacea herb in a solid-liquid system // Scientific Bulletin of the International Humanitarian University, No. 1, 2010, p. 31-35), in which tincture of echinacea purpurea obtained by extraction of Echinacea herb with 40% ethyl alcohol, twice (or thrice), insisting each time for 10-12 hours, with a ratio of raw materials: extractant 1: 6, at 40 ° C. The disadvantage of this method is the insufficient extraction of all target components of Echinacea purpurea.

A known method of obtaining tincture of Echinacea GalenoPharm (series 20213) obtained by water-alcohol extraction of grass Echinacea purpurea L. 40% ethyl alcohol by fivefold ethyl percolation with a total ratio of raw materials: extractant 1: 5 and with a ratio of raw materials: extractant at each stage of percolation 1: 1, subsequent mixing obtained at each stage of percolation of the extracts and sedimentation of the resulting mixture of extracts for 1-5 days at a temperature of from 8 to 10 ° C (see RU 2163138 C1, 02.20.2001). Tincture can also be obtained using 20% -70% ethyl alcohol. This document is selected as the closest analogue. The technical disadvantage of this method of obtaining is the duration and complexity of the process, the method does not provide the maximum extraction of all target components of Echinacea purpurea.

The purpose and essence of the invention

An object of the invention is the development of a simple technology for obtaining tinctures from Echinacea herb and the creation of a medicinal product based on it while maintaining the biological activity and quantitative values of the components in the case of a decrease in the ethyl alcohol content in the resulting tincture.

The technical result consists in obtaining tinctures from the herb Echinacea while maintaining the biological activity and quantitative values of the components that make up the tincture, while reducing the concentration of ethyl alcohol in the finished product, using simple technology.

The technical result is achieved by implementing the method, which consists in the extraction of crushed Echinacea grass with ethyl alcohol 19-20% in the ratio of raw materials: extractant 1: 6 at a temperature of 20-30 ° C, insist 12-24 hours, then mix for not less than 1 hour, insist another 12-24 hours, drain the extract in an amount equal to the amount of feed loaded, after draining the extract, fresh extractant is added to the processed raw materials in the ratio of raw materials: extractant 1: 1, insist with periodic stirring for 12 hours, then the whole uh strakt emptied; all the extracts obtained are combined and cooling is carried out for 5-8 days at a temperature of 4 to 7 ° C, filtered.

Using this method, a new immunomodulatory, immunostimulating, antimicrobial, anti-inflammatory and antiviral agent is obtained in the form of tincture from the Echinacea herb, while preserving the biological activity of the components that make up the claimed drug and reducing the amount of ethyl alcohol in the finished product using simple technology.

To obtain this tincture use any kind of herb Echinacea.

The resulting tincture from the herb Echinacea contains extractive substances Echinacea and ethyl alcohol, in the following ratio of components, vol.%:

Extractives of the herb Echinacea Not less than 2.0% Sum of hydroxycinnamic acids in terms of chicory acid Not less than 0.2% Ethanol Content No more than 19%

It was experimentally established that it is as a result of this technology claimed as an invention that we obtain the target pharmacologically active components - the sum of hydroxycinnamic acids (chicorye, chlorogenic and kaftaric), while reducing the content of ethyl alcohol and preserving their biological activity and therapeutic properties.

The inventive technology parameters are optimal from the position of providing the ability to extract the target substances from the Echinacea herb while maintaining the properties, qualities and biological activity of the extracted substances and compounds. The tincture obtained by the proposed method has a pronounced immunomodulating, immunostimulating, antimicrobial, anti-inflammatory and antiviral activity, while the ethanol content in it is reduced, without loss of pharmacological activity.

The invention is as follows.

The invention is illustrated by the following examples of practical industrial implementation of the invention.

The extractant (ethyl alcohol 19-20%) is prepared in a reactor with a stirrer. 95% ethanol is fed into the reactor (FSP 57127, FSP 42-9292-08, amend. 1-4, FS-000490-190213) and purified water is fed in the required amount (FS 42-2619-97).

Different types of echinacea were used as plant materials: grass of Echinacea purpurea, or Echinacea angustifolia, or Echinacea dark red, or Echinacea pale.

Ground Echinacea grass (VFS 42-2371-94, EP7 01/2008: 1823, version 6.0, EP7 01/2008: 1824, version 6.0) is loaded into two steel baskets with a perforated top and bottom, which are placed in a percolator (per two baskets in each percolator). The percolator is equipped with a jacket, in order to maintain the maceration temperature in the range from 20 to 30 ° C, sharp steam is supplied to the lower pipe of the percolator to provide the possibility of steam treatment of the spent plant material loaded into the percolator to recover ethyl alcohol.

Two baskets with Echinacea grass are loaded into the percolator, the extractant is extracted with ethyl alcohol 19-20% in the ratio of raw materials: extractant 1: 6 and infused in a closed apparatus at a temperature of 20 to 30 ° C for 12-24 hours, after which the contents are mixed percolator for at least 1 hour, then continue the infusion for 12-24 hours and drain part of the extract equal to the amount of loaded raw materials. After draining the extract, fresh extractant is added to the treated grass in the ratio of raw material: extractant 1: 1. Infusion with periodic stirring is carried out for 12 hours and the entire extract obtained is drained into an intermediate container.

All extracts obtained are combined in a collection and cooling and clarification are carried out at a reduced temperature from 4 to 7 ° C for 5-8 days. An aged tincture is filtered through a cascade of filters with different pore diameters.

The finished tincture of Echinacea is served on packaging in bottles of orange glass with a screw neck type ФК, ФКМ, ФВ-30-20, ФВ-50-20, ФВ-100-20, sealed with plastic caps or stoppers-droppers and screwed caps made of polymeric materials .

The spent raw materials are treated with hot steam in order to regenerate ethyl alcohol from the spent raw materials, for which the percolator is tightly closed, water vapor is fed into the apparatus. Alcohol distillates are condensed in a refrigerator and collected for reuse as extractant.

The resulting tincture of echinacea is a clear liquid without foreign matter from tan to brown with a density of from 0.9747 to 0.9800 g / cm ³ . During storage, the appearance of a flocculent precipitate or sediment in the form of a dark coating on the bottom and walls of the bottle, which, when shaken, breaks, or the formation of non-breaking coating on the bottom and walls of the bottle.

With this type of extraction, the concentration of extractives of various types of Echinacea in tincture in vol.%: Not less than 2.0%, including the content of the amount of hydroxycinnamic acids in terms of chicoryic acid not less than 0.2% and the ethyl alcohol content not more than 19% , which is confirmed by the results below. The shelf life of tinctures is 3 years.

The method of applying tinctures of Echinacea is as follows.

Means for the treatment and prevention of acute respiratory viral infections and acute respiratory infections. Inside. Shake well before use. Adults and children over 12 years of age 25-35 drops 3 times a day before meals. Children from 2 years to 6 years of age are prescribed 5-10 drops three times a day, and children from 6 to 12 years old - 10-15 drops three times a day. The duration of one course of treatment should not exceed 8 weeks. The average duration of treatment is 2-3 weeks.

Accounting and interpretation of results

The determination of quantitative and qualitative indicators of the obtained tincture is carried out as follows:

Test 1: The solids content in the tincture is determined by the method described in GF XI, no. 2, p. 149. The solids content should be at least 1.7%.

Test 2: 1 ml of the drug is placed in a volumetric flask with a capacity of 50 ml, adjusted with ethyl alcohol 40% to the mark.

10 ml of the resulting solution is transferred into a volumetric flask with a capacity of 50 ml, adjusted with ethyl alcohol 40% to the mark. The contents of the flask are thoroughly mixed (test solution).

The optical density of the test solution is measured on a spectrophotometer at the maximum absorption at a wavelength of 328 nm in a cell with a layer thickness of 10 mm

The UV spectrum of the prepared drug solution in the region from 200 to 400 nm should have a maximum absorption at a wavelength of (328 ± 2) nm, a minimum absorption at (265 ± 2) nm and an inflection in the region (300-310) nm.

Test 3: The ethyl alcohol content in the tincture is determined by the method described in the Global Fund XI, vol. 1, p. 26. The content of ethyl alcohol in the tincture should be no more than 19%.

It was experimentally established that the proposed tincture does not have an irritating and sensitizing effect and is non-toxic.

The immunomodulating, immunostimulating, antimicrobial antiviral and anti-inflammatory effect of the proposed agent, characterized by the method of its preparation, is due to the presence of components of extractive substances, in particular hydroxycinnamic acids and their glycosides (chicorye, ferulic, coumaric, caffeic acids, echtinacin, echinocoside substances, etc.). , saponins, flavonoids, carbohydrates and other biologically active compounds.

Biologically active substances of tincture enhance the phagocytic activity of granulocytes and RES cells, induce the synthesis of acute phase cytokines and proteins, stimulate the activity of natural killer cells (NK cells), which suggests the presence of mediated antimicrobial, anti-inflammatory and antiviral activity. Also, with the clinical use of tincture of Echinacea purpurea, an increase in the activity of lysozyme and complement in the blood serum of patients has been established.

A study of the effect of tincture of echinacea, obtained on the basis of the proposed method, on phagocytosis in vitro and in vivo, showed that it stimulates the chemotactic mobility of granulocytes in the Boyden chamber by 45%, enhances the absorption of yeast-like fungi Candida albicans by granulocytes and healthy monocytes by 30-45% donors, however, does not affect the intracellular killing of phagocytosed fungi, and therefore exhibits immunostimulating properties.

Thus, our technology for obtaining tinctures from Echinacea herb allows you to get a therapeutic agent in a simple way, with the biological activity of the components that make up the tincture, while reducing the concentration of ethyl alcohol in the manufacturing process and in the finished product.

Claims (3)

1. The method of obtaining tinctures from Echinacea herbs, which consists in extracting the crushed Echinacea herbs with ethyl alcohol 19-20% in the ratio of raw materials: extractant 1: 6 at a temperature of 20-30 ° C, insist 12-24 hours, then mix in for at least 1 hour, insist another 12-24 hours, drain part of the extract equal to the amount of raw material loaded, after draining the extract, add fresh extractant to the treated grass in the ratio of raw material: extractant 1: 1, hold for 12 hours with periodic stirring, the entire extract drained; the obtained extracts are combined and cooling is carried out for 5-8 days at a temperature of 4 to 7 ° C, filtered. 2. The use of the method according to claim 1 for obtaining tinctures from the herb Echinacea, which has immunomodulating, immunostimulating, antimicrobial, anti-inflammatory and antiviral activity. 3. Tincture of the herb Echinacea, with immunomodulating, immunostimulating, antimicrobial, anti-inflammatory and antiviral activity, obtained by the method according to p. 1.