Means, possessing anti-tuberculosis action

FIELD: medicine.

SUBSTANCE: means represents a dry extract of leaves and flowers of Gratiola officinalis, obtained by milling the leaves and flowers of Gratiola officinalis, extraction with 96% alcohol on a water bath to boiling and boiling, evaporation, dilution of the evaporated residue first with distilled water, then by the addition of chloroform, cooling to room temperature and centrifuging with the following separation of a water fraction and drying it under specified conditions.

EFFECT: means is non-toxic, has an expressed anti-tuberculosis action.

2 tbl, 2 ex

 

The invention relates to medicine and pharmaceutical industry, namely to creation of drugs based on novogalenovyh preparations possessing antitubercular aktivnosti. and can be used for preclinical and clinical trials for the treatment of tuberculosis, including those caused by resistant strains of M. tuberculosis to many drugs.

Tuberculosis is one of the highest priorities of modern medicine (Priymak A. A. Thoughts on TB // Pulmonology - 2005. - S. 35-38; TB national guidelines / ed. by M. I. Perelman. - M.: GEOTAR. - 2007. - 752 p.). In recent decades, the importance of this issue has increased in connection with the formation of the high resistance to the treatment of tuberculosis (Tuberculosis / edited by B. bloom. - M.: Medicine, 2002. - 677 S.). One of the main reasons for the epidemic of TB worldwide is the spread of drug-resistant forms of the disease, difficult to treat a limited set of known TB drugs.

Treatment of patients with drug-resistant TB, especially multidrug resistance (MDR), at least to the two main drugs - isoniazid and rifampicin - requires significantly more costly and long�individual treatment using drugs often causing serious adverse reactions (Tuberculosis in the Russian Federation 2011 Analytical review of statistical indicators used in the Russian Federation and in the world. - M., 2013; Vasilyev A. V., Grishko, A. N. // TB and the city: problems of prevention, diagnosis and treatment. - SPb., 1996. - P. 9-16). These reactions showed pronounced hepatotoxic effect, as well as nausea, vomiting, pain in the heart, psychosis, appearance of peripheral neuritis with atrophy of the muscles and paralysis of the limbs, etc. in addition, contraindications to the appointment of a number of medicines are diabetes, inflammation of the optic nerve and the eye, pregnancy, infancy, etc. All this necessitates the search for new safe antibacterial agents with anti-TB activity (drugs: a guide to pharmacotherapy for physicians: (2 T.) / M. D. Mashkovsky. - 11th ed., erased. - M.: Medicine. Part 1. - 621 p.). One of the sources of non-toxic medicines of antimicrobial activity, including against resistant to known drugs of microorganisms, may be extracts from medicinal plants (mprm).

Abraham officinalis (Gratiola officinalis L.) is a herbaceous plant of the Figwort family, is widely distributed in Eurasia and North America. Rastenie.org poisonous. The quality of the raw materials of Hauran regulated medicinal Pharmacopoeia article 42-2358-85. The earlier grass of the Hauran was a part of the collection Zdrenko as a symptomatic agent in the treatment of papillomatous gastritis and was used as a laxative, anthelmintic, cardiotonic, choleretic and antiseptic (Mashkovsky M. D., Babayan E. A., Abolmasov A. N., Bulaev, V. M., Severtsev S. D., ANCOVA A. I. the State Pharmacopoeia of the Union of Soviet Socialist republics. M.: Medicine, 1989. 2 edition. Issue 2. 400 C.; http://www.dorogaistin.ru>index.php). Mainly used water extracts of herbs and 15% alcohol tincture (http://www.dorogaistin.ru>index.php). Of extract obtained from the herbs of the Hauran have high toxicity, so when the domestic application was used together with the mucous decoctions, great caution and under medical supervision (http://www.travolekar.ru/articles.php).

Different methods of extraction from the same raw material can lead to obtaining biologically active compounds (BAC) with different chemical compositions and properties (Ponomarev, V. D. Extraction of medicinal raw materials. Medicine. 1976. 186 p.). So, upon receipt of the extract from raw materials of Hauran through raw material extraction in 96% ethanol (or methanol or n/a(ISO)-propanol and chloroform (Pat. 1063118 (A) Great Britain, IPC 7 AC 36/00 AC 36/80. Plant extract / MEN JEANLE.; the applicant and the patentee ROGER BELLON. - No. GB 19640048825; Appl. 01.12.1964; publ. 30.03.1967), which is obtained and used chloroform fraction with non-polar compounds, including toxic compounds (alkaloids and glycosides), extractives remain toxic. Furthermore, the extract obtained by this method has a significant laxative effect, due to the content of toxic substances - alkaloids and glycosides, providing the irritating effect on the intestines, thereby sharply reduced the scope of its application. There are also known methods of obtaining water infusions, alcohol tinctures, and extracts from raw materials of Hauran, including the use of ethanol in different concentrations and chloroform, which extracts from the Hauran contain glycosides Graziosi (Grazioli), graziottin, cucurbitacin glycoside laterized, fatty oils, saponins, Apple and betulinic acids, carbohydrates (stachyose), terpenoids (laterized, deacetylating, cucurbitacin E and I), cardenolides, saponins, flavonoids (lignose, isaligned, apigenin, cosmosign, lignose, eurosid, sauroid, neweurasia, isoniazid), as well as alkaloids (0.2%) of yet undetermined composition, in different proportions, depending on the allocation method (http://www.travolekar.ru/articles.php; GB 1063118, 01.12.1964; US 5.804.575. 1997; Ruzicka L., A. H. Lamberton, Christe C. W. Ruzick Synthetic approach to betulinic acid. Helv. Chim. Acta. 1938. Vol.21. P. 1706-1717; Kurkin, V. A. Pharmacognosy: a Textbook for students of pharmaceutical universities. Samara: LLC "Etching" Samara state medical University, 2004. 1180 S.; Alferov A. H. Herbal medicine against cancer. St. Petersburg: Publishing House Of The Wings. Series: XXI century Medicine. 2010, 240 p.).

Among other drugs from plant material of known water-alcohol extract of the roots and aerial parts of Glycyrrhiza glabra Glycyrrhiza glabra, has a pronounced anti-TB activity (patent No. 2362577, 2007, Sukhenko L. T., Urlaeva N. G., Nazarova G. N.), containing triterpenoid saponin glycyrrhizin, CA and K salts of glycyrrhizic acid (20-30%); glycyrrhetic acid (10-20%), including compounds of the group of flavonoids. The activity of this extract is a relatively high - concentration of less than 2.5×10-4mg/ml active compounds completely inhibited the growth of the office.

The disadvantage of this extract of the roots and aerial parts of Glycyrrhiza glabra Glycyrrhiza glabra is a high content of glycyrrhizin and glycyrrhizic acid, which are known (Licorice root. Description of the drug in the Handbook Vidal), violate the metabolism of cortisol in the body, which contributes to the development of pseudoaldosteronism and can lead to cardiovascular disease. In addition, in the process of obtaining the extract was subjected to autoclaving, resulting in under the action�m high temperatures many active components (incl. flavonoids), which could exert antioxidant action, has been destroyed, and in the treatment of tuberculosis is not unimportant aspect is the reduction of intoxication, as this disease, as is well known, the development of secondary amyloidosis and cachexia.

It is also known (RU 2223107, 05.09.2007) possessing antitubercular activity that contains aloe leaf (Aloe perfoliata L.), rhizome of calamus (Acorus calamus L.), birch leaves (Betula pendula L.), hibiscus flowers (Hibiscus moscheutos L.) rhizomes and roots of elecampane (Jnula helenium L.), Linden flowers (Tilia cordata Mill.), schisandra berry (Schisandra glabra (Brickell) Rehder), nettle leaf (Urtica dioica L.), grass violets (Viola tricolor L.), peppermint leaf (Mentha xpiperita L.), licorice root (Glycyrrhiza glabra L.), horsetail grass (Equisetum arvense L.) and grass Bur-marigold (Bidens tripartita L.). Phytochemical analysis of the funds have established the presence of such biologically active substances as flavonoids, tannins, polysaccharides, saponins, essential oils, vitamins, organic acids. The main biologically active component are flavonoids and polysaccharides.

The disadvantage of this composition is the inability to reliably identify chemical compounds that have had a TB action. Extraction to obtain the dry extract was carried out at a temperature of 90-95 degrees, which has a destructive effect on flavonoids, the statement� as one of the key active ingredients of this composition.

The analysis of literature showed that the benefits of plant extracts have received a multistage method of cleaning ballast from compounds aimed at increasing the yield of certain compounds with a particular action. One of the promising groups of antimicrobial action are bioflavonoids {Kurkin V. A. Pharmacognosy: a textbook for pharmaceutical universities (faculties) / V. A. Kurkin / 2-e Izd., revised and enlarged. Samara, 2007. - S. 1239), which is a plant phenolic compounds with a wide spectrum of biological actions.

This paper reviews the extract obtained by us earlier in a way to obtain non-toxic extractives from poisonous plants (RU 2482863, 15.02.2012). For extract obtained from the herbs of the Hauran we have already described the positive effects on animals with transplanted liver cancer and, at the same time, a negative impact on tumor cells, which is manifested in the form of cytotoxic and cytostatic effects (Polukonova N. In., Merkulova E. P., Durnova N. And., Romantseva Y. V., Borodulin V. G. Study of antioxidant activity of the extract of Abraham officinalis in rats intertwined with liver tumor PC-1 // Theses of reports of scientific-practical conference "Biologically active substances: fundamental and applied in�issues of production and application". Novy Svet, Crimea, Ukraine, 23-28 may 2011. Kiev. 2011. S. 585; Navoloki N. And., Pavlov A.V. Morphological changes in muscles in laboratory rats and determination of toxicity when administered extract of Hauran // Bulletin of medical Internet conferences. 2012. T., Vol. 2. - P. 82-83; Navolokin N. A., Polukonova N. V., Maslyakova G. N., Bucharskaya A.V., Durnova N. A. Effect of extracts of Gratiola officinalis and Zea mays on the tumor and the morphology of the internal organs of rats with trasplanted liver cancer //Russian Open Medical Journal 2012. P. 1-4. http://www.romj.ors/2012-0203).

Studies antitubercular activity Abraham officinalis herb available in us literature.

The technical object of the present invention is to expand the Arsenal of tools from vegetable raw material having anti-TB activity, more affordable and non-toxic.

The advantage of the proposed dosage of the extract is low toxicity and availability of raw materials from which the tool, the presence of antioxidant activity and total positive effect on the body, which is an important aspect in the treatment of tuberculosis.

We first determined the properties of the tool, which is a dry extract of leaves and flowers of Abraham officinalis, obtained by grinding, extraction with alcohol 96%, evaporation of the extract, the addition of chloroform, removing the chloroform, and alcohol extraction PR�lead in a water bath to a boil and boil for 14-15 minutes evaporated at a temperature of 55-60°C, the evaporated extract was diluted first with distilled water 40-50°With, then add chloroform in the proportion of part 4/5 water and 1/5 parts of chloroform, cooled to room temperature and centrifuged at a speed of 1500 rpm for 15 minutes, then the aqueous fraction is separated and dried her. Obtained biological active composition has a new feature: anti-TB activity.

The means obtained in this way from the Hauran drug has the following chemical structure: 4-vinyl-2-methoxyphenol; 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-Piran-4-it; 2,3-dihydrobenzofuran; 3-francebuy acid; 5-gidroximetil-2-furaldehyde; ethyl-α-d-ribozid; 4-propylene; catechol; L-Lukasa (pentose); 6-deoxyhexose L-galactose; benzoyloxy acid ethyl ester; hexadecanoate acid (palmitic acid); gomovanilinovoi acid; glucose; 1,4-angidro-d-mannitol; benzoic acid; quercetin.

The thus obtained extract is a biologically active composition with new pharmacological properties of TB, previously known as the plant of Hauran medications described above for the funds.

The preparation is a dry extract, yellow-brown, mixed with water and ethyl alcohol for any ratios.

The parameters of authenticity and quality tools.

The authenticity of the drug is confirmed by the qualitative reactions to the content of flavonoids and absence of alkaloids in the aqueous solution of the dried extract of Hauran.

Qualitative reactions for flavonoids: to 1 ml of drug is added 1 ml of purified water, 10 mg of the crystal of magnesium and 5 drops of acid hydrochloric concentrated, heated in a boiling water bath for 3 min, appeared red-brown staining, the positive sample of the Synod, which indicates the content in the solution of flavonoids.

Qualitative tests for alkaloids: a) with a reagent Wagner-Bouchard negative (in the presence of alkaloids in the solution should turn yellow); b) with a solution of 1% picric acid negative (in the presence of alkaloids in the solution should be yellow); C) with an acid solution phosphomolybdenum negative (in the presence of alkaloids in the solution becomes cloudy).

All 3 qualitative reactions is negative, therefore, the resulting extract has no alkaloids.

Compared to the previously obtained aqueous and alcoholic extracts of the herb Hauran we received the evaporated extract of leaves and flowers of the Hauran is non-toxic, due to the chemical composition and confirmed previously in rats (N. A. Navolokin, N. V. Polukonova, G. N. Maslyakova, A. B. Bucharskaya, N. A. Dumova / Effect of extracts ofGratiola officinalis and Zea mays on the tumor and the morphology of the internal organs of rats with transplanted liver cancer // Russian Open Medical Journal 2012; 1: 0203).

The definition of antitubercular action of Abraham officinalis extract.

The definition of anti-TB effect of the extract was carried out according to standard methods of evaluation of drug resistance of Mycobacterium tuberculosis (MBT) on thick egg nutritional löwenstein-Jensen medium containing no starch (HiMedia, India) by the absolute concentration method (order of the MOH, 2003; Leadership training materials for experimental and clinical study of new drugs. H. 6, Moscow, 1986) with some modifications. Own modification of the standard method was to replace the absolute concentration serial dilution to determine the threshold concentrations of the extract, to overcome which the growth of M. tuberculosis was determined.

Analysis was performed on the following strains: first - the Museum strain H37 RV that does not have antibacterial resistance (to determine the dynamics of growth and feasibility of further research), and strains having a resistance, for which the methods of bacteriological examination (by the absolute concentration method) previously, we identified the degree of resistance of clinical strains to anti-TB first line drugs (rifampicin, isoniazid, streptomycin and ethambutol).

The strains of bacteria tuberc�Lesa with varying degrees of drug resistance were obtained when sowing respiratory material (sputum) from patients undergoing treatment in the health facility "Tambov regional clinical TB dispensary". Of these, the first strain was sensitive to the following drugs: isoniazid, rifampicin, streptomycin and ethambutol and designated as sensitive strain. The second strain was resistant to anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol), as determined by culture, therefore, is designated as MDR strain.

Culture of mycobacteria were regarded as resistant to this concentration of the drug only in the presence of the test tube with the concentration of 20 colonies or more if excessive growth in the control tube containing no drug.

Investigated the growth dynamics of the Museum of the strain under the action of Hauran drug at a concentration of 14 mg/ml. the Observations were carried out within 30 days, but was inoculated on a nutrient medium 2 titer cells ILO corresponding to 50×107and 500×107microbial bodies in 1 ml.

Culture, assessed as resistant to the main anti-TB drugs, were tested using gene molecular methods (hybridization on the biochip "TB-BIOCHIP") to identify mutations that caused resistance. Molecular genetic study analyzed MDR strains was performed using the method of hybridization on bi�chips "TB-BIOCHIP" (LLC "Biochip-IMB", Russia) according to the method recommended by the manufacturer. The method includes DNA isolation of M. tuberculosis from respiratory specimens, carrying out two sequential multiplex PCR, hybridization of amplification products of the second stage PCR for the biochip. The hybridization results were recorded on a portable biochip analyzer (LLC "BIOCHIP-IMB", Russia) with the appropriate software. As a result, the MDR strain is resistant to rifampicin (gene Codon 531 of the rpoB gene; amino acid substitution Ser→Leu) and isoniazid Codon of the gene katG 315; amino acid substitution Ser→Thr(1))

In the study of active bacteriostatic/bactericidal concentrations was laid four lines of cultures: the first line consisted of a positive control (a series of four test tubes with each strain separately without impact), the second line is a row of four tubes without seeding strains to prevent accidental growth of the office (negative control). The third and fourth lines were experimental (culture with two clinical strains) and contained six test tubes with different dilutions of the extract.

The minimum inhibitory concentration (IPC) of the extract of Hauran on resistant strains was performed by the method of serial dilutions on thick egg löwenstein-Jensen medium containing no starch (manufacture HiMedia, ind�I) {Ministry of health order No. 109, 2003). The aqueous solution of the dry alcoholic extract was added to the medium during its preparation at a temperature of 20-25°C. the office were seeded in a standard titer (cell concentration corresponding to 1×107microbial bodies). Controlling the growth of colonies of Mycobacterium tuberculosis was performed for 28 days (Ministry of health order No. 109, 2003).

Studying the dynamics of growth of the Museum's strain of M. tuberculosis under the action of Abraham officinalis extract.

In both replicates, there was a complete absence of colony growth of the office on Wednesday with the addition of an extract of Hauran within 28 days under the title of the office 50×107(bactericidal effect), while in the control groups, the growth of colonies was observed at 10 days (table.1). When the titer office 500×107the first repetition was observed bactericidal activity (no growth at all periods of observation) and in the second repetition of a single colony of the office on Wednesday with the addition of an extract of Hauran appeared only on the 10th day of observation, while in the control with 7 days showed moderate growth, while 10 day abundant growth of colonies (2+ and 3+ respectively).

The lack of growth in MW on the medium with the addition of Abraham officinalis extract in both provonost at a titer of office 50×107in the first repetition at the title office 500×107from 1 to 28 days of observation compared to the control, indicates the presence of pronounced BA�terezinho effect of the extract of Hauran. The emergence of weak growth in the titer office 500×107in the second repetition with 7 days and the preservation of weak growth (less than 20 CFU) up to 28 days under the action of the extract, compared to control said about the bacteriostatic effect of extract of Hauran medicinal strain on the Museum office.

Table 1
Dynamics of growth of the Museum's strain of M. tuberculosis under the action of Abraham officinalis extract
RepetitionThe days of observationsday 7day 10day 1728 day
The titer ICD50×107500×10750×107500×10750×107500×10750×107500×107
1Control--+ +++++++++++++
The extract of Hauran--------
2Control-+++++++++++++++++++
The extract of Hauran---+-+-+
(COE)(COE)(LE)
Note: (1+) - 1-20 SOME ACS�th rise office
(2+) - 21-100 SOME moderate growth MBT
(3+) - more than 100 SOME heavy growth MBT

We found that when the concentration of the extract of 13.3 mg/ml, a marked bacteriostatic effect on sensitive clinical strain (without MDR), and 26.6 mg/ml bactericidal effect in accordance with the evaluation criteria of the sensitivity of the office.

When the concentration of the extract 26.6 mg/ml notes bacteriostatic action (18 CFU) of the extract on MBT strain MDR, and at a concentration of 53 mg/ml, there is complete suppression of growth of cultures ILO MDR (bactericidal action) (Tab. 2).

Thus, Abraham officinalis extract in a concentration of 26.6 mg/ml has a bactericidal effect on clinical strain is sensitive to anti-TB drugs, and bacteriostatic clinical MDR strain. The bactericidal effect of the MDR strain is observed with the concentration of 53.1 mg/ml.

Table 2
Analysis results of antitubercular activity of Abraham officinalis extract on clinical strains
The concentration of extract in the medium(mg/ml) The light of the resultNo. culture test
Sensitive strainStrain MDR
the number of CFU* in control95%95%
212.5the number of CFU--
the resultSS
106.3the number of CFU--
the resultSS
53.1the number of CFU--
the resultSS
26.6the number of CFU-18
the resultSS/R
13.3the number of CFU 235
the resultSR
6.6the number of CFU3080%
the resultRR
Note: *the Number of SOME specified if it can be calculated. When SOME large number, impossible to count, approximate proportion (%) of the surface of the medium with the growth of the office. Result: S - strain sensitive, R - resistant strain.

Thus, the obtained extract of Abraham officinalis possesses anti-TB activity in vitro. We have proved the high TB (bacteriostatic and bactericidal) activity of the extract of Hauran drug studied in vitro. This effect was shown how strain on the Museum with the assessment of the dynamics of colony growth, and using the method of serial dilution on the MDR strains. We have identified the IPC minimum inhibitory concentration of the extract of Hauran on the strains with and without MDR. Thus, when the concentration of Hauran in the medium 14 mg/ml there was a complete bactericidal effect in relation to the Museum of the strain of the office and when 53,1 mg/ml there is a complete basement�their growth MBT cultures MDR, that is definitely promising ground for further study of the action of Abraham officinalis extract containing flavonoids, in experimental models of tuberculosis, and later at the clinical level in the development of effective ways and forms of delivery extract of the patient's organism.

Therefore, this extract may be recommended and considered for pre-clinical studies for the treatment of tuberculosis, including can be a promising drug for the treatment of multidrug resistance, as a standalone drug or in combination therapy with other anti-TB drugs.

Example 1.

The leaves and flowers of the Hauran was ground and sieved through a sieve with a mesh size of not more than 3 mm. Weigh 10 g of the crushed material, put it into a flask of 500 ml, was added 100 ml of ethyl alcohol 96%, in a water bath brought to boiling and boiled for 14 min. Extract of the flask was filtered in a glass bowl using 4 layers wide bandage, the rest of the plant material is carefully pressed, poured another 100 ml of ethanol 96%. Brought to the boil and again filtered in the same glass container. The resulting extract was evaporated to dryness in a thermostat at 55°C. In a glass container � evaporated extract was added 8 ml of t of distilled water, then use the syringe the resulting solution was transferred into a plastic centrifuge tube with a volume of 11 ml, was added 2 ml of chloroform, shake a few times until homogeneous, cooled to room temperature and centrifuged for 15 min (to remove nonpolar impurities (chlorophyll), etc.) at a speed of 1500 rpm. The aqueous fraction was collected with a syringe, placed into pre-weighed Petri dish, dried and in this form was stored before the experiment. Weight of dry extract was calculated as the difference between the weight of the Petri dish with dry extract and a weight of empty Petri dishes. Received 225 mg of dry extract of Hauran.

On thick egg nutritional löwenstein-Jensen medium containing no starch (HiMedia, India) was sown Museum strain of M. tuberculosis (order of the MOH, 2003; Leadership training materials for experimental and clinical study of new drugs. H. 6, Moscow, 1986). The aqueous solution of the dry alcoholic extract was added to the medium during its preparation at a temperature of 20-25°C, evenly distributing it with a final concentration in the medium 14 mg/ml. MBT seeded in a standard titer (cell concentration corresponding to 50×107microbial cells /ml). 28 day growth of mycobacteria was not defined.

Example 2.

The extract obtained by the method described in example 1, was investigated n� clinical strain of M. tuberculosis.

On thick egg nutritional löwenstein-Jensen medium containing no starch (HiMedia, India) was sown clinical strain of M. tuberculosis resistant to anti-TB first line drugs (isoniazid, rifampicin, streptomycin and ethambutol) (Ministry of health order No. 109, 2003; Leadership training materials for experimental and clinical study of new drugs. H. 6, Moscow, 1986). The aqueous solution of the dry alcoholic extract was added to the medium during its preparation at a temperature of 20-25°C, evenly distributing it with a final concentration in the medium (100 mg/ml. the office was inoculated with a titer content of cells corresponding to 1×107microbial cells /ml At 28 days growth of mycobacteria was not defined.

Thus, the extract obtained by extraction with 96% ethanol leaves and flowers of Abraham officinalis, under certain conditions, with chloroform purification from toxic substances with their subsequent removal together with the solvent by centrifugation, evaporation of water fraction in a water bath at a temperature not exceeding 60°C, has a new feature - bactericidal and bacteriostatic effect on M. tuberculosis, including resistant to standard anti-TB first-line drugs (isoniazid, rifampicin, streptomycin and ethambutol), with extra�t is not toxic and has antioxidant activity.

A means of having anti-TB activity, representing a dry extract of leaves and flowers of Abraham officinalis obtained by grinding the leaves and flowers of Abraham officinalis, extraction with alcohol 96% in a water bath to a boil and boil for 14-15 minutes, evaporation at a temperature of 55-60°C, dilution of evaporated residue first with distilled water at a temperature of 40-50°With, then add chloroform in the proportion of part 4/5 water and 1/5 parts of chloroform, cooled to room temperature and centrifugation at a speed of 1500 rpm for 15 minutes followed by separation of the aqueous fraction and drying it.



 

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2 dwg, 12 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical and consumer industry in preparing dry herbal extracts used for later colouration of textile fabrics with this extract. A method for preparing the dry herbal extract of St. John's wort involves grinding herbal raw material, extracting in water, filtering, boiling down in a rotary evaporator and drying the residual product to constant weight in a drying chamber in the certain environment.

EFFECT: method described above enables preparing the extract with dry colorant weight 25% of dry herbal raw material weight.

FIELD: medicine.

SUBSTANCE: agent is presented in the form of a tablet, contains isoniazid and a substance which reduces its toxicity; as the substance which reduces the isoniazid toxicity, it contains thiotriazolin. The isoniazid/thiotriazolin ratio makes 4:1.

EFFECT: combined antituberculous drug ensures reducing toxicity as compared to the known ones and increasing its pharmacological activity.

2 cl, 1 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a chemical compound of formula wherein R=benzyl and to an antituberculous therapeutic agent representing a composition of imidazo[1,2-b][1,2,4,5]tetrazine derivative of formula I, wherein R=benzyl, isopropyl or phenyl and the known antituberculous preparation pyrazinamide with the ingredients in mole ratio 1:1.

EFFECT: there are prepared new antituberculous therapeutic agents.

2 cl, 2 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to nitroimidazooxazine derivatives of general formula I, where n equals 1, V and W independently denote H or CH3, and one of X and Y is H and the other is one of the formulae and , where formula IIa includes a single ring labelled at position 3 and position 4 and containing R1 as a substitute, and formula IIb includes a first ring labelled at position 3 and position 4 and containing as substitutes both R2 and a terminal ring, labelled at position 4 and containing R1 as a substitute, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb include C, CH, or N at each ring position, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb independently contain no more than two nitrogen atoms; Z in formulae IIa and IIb is CH2 or a direct bond, R1 is independently any one or two of H, F, C1, CF3, OCF3 or OCH2Ph, and R2 is H. The invention also relates to a pharmaceutical composition based on the compound of formula I, a method of preventing and treating a microbial infection based on use of the compound of formula , and specific nitroimidazooxazine derivatives.

EFFECT: obtaining novel compounds with useful biological activity.

7 cl, 21 dwg, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of genetic engineering, molecular biology and vaccinology. Claimed is polyepitopic anti-tuberculosis vaccine construction for formation of immune response, which provides induction of immune response of CD8+ T-lymphocytes, consisting of universal polyepitopic immunogen, containing CTL-epitopes, selected from immunodominant antigens of M. tuberculosis, fused from N-end with ubiquitin, and having amino acid sequence SEQ ID NO: 1.

EFFECT: vaccine construction provides achievement of effective therapeutic T-cell immune response not only due to antigenspecific cytotoxic CD8+ T-lymphocytes but also intensive response of CD4+ T-lymphocytes.

1 tbl, 11 dwg

FIELD: medicine.

SUBSTANCE: invention concerns Mycobacterium tuberculosis growth inhibitors representing (+) and (-)-enantiomers of derivatives of usnic acid containing a furilidene furanone fragment, namely (10R,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4a and (10S,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4b

EFFECT: inhibitors possess the high antimicrobial activity.

2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of 1-(2-chloroquinolin-3-yl)-4-dimethylamino-2-(naphthalen-1-yl)-1-phenylbutan-2-ol of general formula I or their pharmaceutically acceptable salts with acids, where R1 denotes H, R2+R3 denotes -O-(CH2)n-O-, where n=1-2, which forms additional dioxane and 1,3-dioxolane rings. The invention also relates to a method of producing a compound of formula I and to use of the compound of formula I in treating infectious mycobacterial diseases.

EFFECT: obtaining novel compounds with useful biological activity.

4 cl, 2 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: for treatment of patients with pulmonary tuberculosis with accompanying non-specific bronchitis at the background of carrying out standard anti-tuberculosis therapy from the first day of treatment additionally daily for 3 months the preparation Wobenzym is introduced in a dose of 1 tablet 2 times per day, 30 minutes before meal, and inhalation with a solution of the preparation Hixozide in a dose of 350 mg in 10 ml of water for injections is performed 2 times per week, the course constitutes 24 procedures.

EFFECT: method makes it possible to increase treatment efficiency by indices of infiltration resorption, closing of the decay cavities and abacillation.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: for complex therapy of the first time identified pulmonary tuberculosis traditional anti-tuberculosis therapy is carried out. After two weeks of anti-tuberculosis chemotherapy, complex physiotherapy is performed. In the morning 40-60 minutes after meal ultrasound inhalation with an inhibitor of proteases contrykal in a dose of 5000 UNITS, diluted in 3-4 ml of an isotonic solution of sodium chloride is carried out. Inhalation is carried out at a temperature of the solution of 35°C for 10 minutes on the apparatus "Vulkan-1". 20 minutes after inhalation magnetic infrared laser therapy (MIL-therapy) is performed from the apparatus "Rikta-04/4" on affected zones of the lungs by contact method of the application of the apparatus emitter. Frequency of the laser impact constitutes 5-50 Hz. Average power of infrared light-diode radiation is 60±30 mW, an impact with constant magnetic field is realised with induction 35±10 mT for 1-5 min. The course of treatment constitutes 30-40 daily procedures as well.

EFFECT: enhancement of infiltration resorption, closing decay cavities in the shorter period, arrest of intoxication symptoms by the end of the first month of treatment, reduction of terms of elimination of clinical and laboratory manifestations of tuberculosis.

3 cl, 2 ex

FIELD: medicine.

SUBSTANCE: drug preparation for treating tuberculosis contains an active substance isoniaside, and a pharmaceutical carrier tiozol gel with the isoniaside concentration of 5.7-54.5 wt % and the tiozol gel concentration of 45.5-94.3 wt %.

EFFECT: higher clinical effectiveness in tuberculosis and lower toxicity.

2 cl, 2 tbl

FIELD: chemistry.

SUBSTANCE: claimed is a cocrystalline form of fenbufen with pyrazinamide, where molar ratio of fenbufen with pyrazinamide constitutes 1:1, which has an endothermal peak from 148 to 152°C by the data of measurements by means of differential scanning calorimetry and peaks at 2θ(°) 7.38, 10.43, 11.04, 21.67 by the data of measurement of polycrystal X-ray radiation diffraction.

EFFECT: increased rate and level of solubility of the crystalline form of fenbufen and its suitability for application in the pharmaceutical industry.

2 ex, 7 dwg

FIELD: cosmetology.

SUBSTANCE: invention is a natural cosmetic oil for face and body skin care, based on olive plant oil, sterilized under conditions of water bath, where the olive plant oil is used as highly purified first cold pressed olive oil, sterilized under conditions of water bath, with the temperature made up to 100°C, for 5-7 hours and treated for 30-40 min using the device with ultra-small electricity values ranging from 100 to 500 nA to the pH 5.1-5.5 of the final product.

EFFECT: expanding the arsenal of means for face and body skin care.

2 ex

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