Method for making preparation of jagel-m with antituberculous action

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to a preparation with antituberculous action. The method for making the preparation with antituberculous action, characterised by that a dried blastema of sort Cladonia is mechanically treated with solid sodium alkali added. The prepared dry mixture is drawn in an aqueous-alcoholic mixture under certain conditions. The solution is separated from sediment by centrifugation and neutralised with citric acid.

EFFECT: produced preparation shows improved antituberculous action.

1 dwg

 

The invention relates to the biopharmaceutical industry, namely the production of Biologicals anti-TB activity. The use of mechanochemical technologies in the technological cycle of production of antibiotic from the thalli of lichens at the stage of processing of dry materials and the subsequent water-alcohol extraction allow to allocate more complete group of natural substances with antibiotic activity (PVAD).

Lichens of the genus Cladina (Cladonia) - medicinal plants used in folk medicine for treatment of many diseases. In the thalli of lichens contain up to 80% carbohydrates, half of which is represented by homopolysaccharides latinam and selegiline with as immunomodulatory, anticancer and hepatoprotective properties

Aware of the use of lichens as antibiotic funds. So, antimicrobial antibiotic activity against staphylococci, streptococci, acid-fast bacilli, fungi, protozoa and viruses due to the presence in the thalli of the lichen acids [Galitsky L.A., etc. // Probl. the tubes. - 1997. No. 4. - P.35-38], first of all, usninovoy acid (Fig.) and its derivatives [Gorshkov R.P., etc. // Bioorgan. chemistry. - 1997. - Volume 23, No. 2. - S-1328].

Fig. The General formula STS the new acid.

Obtained from lichens usnic acid in the form of usniate sodium was proposed under the name of "Binan" for medical use and was used as an external tool for the treatment of wounds, burns, fractures and gynecology. With the advent of synthetic and semi-synthetic antibiotics drug was discontinued [Teletel VV Useful plants of Central Siberia. - Irkutsk. - 1987. - P.21-22].

The closest analogue of the present invention (the prototype) is the anti-TB drug with a wide spectrum of pharmacological action ISlate" (dry extract of the thalli tsetrarii Icelandic), which has tonic, anti-inflammatory, antimicrobial, antihypoxic, immunomodulatory, hepatoprotective and antioxidant effects [Vitovsky M. etc. the Role of Isleta (extract of the thalli tsetrarii Icelandic) in the treatment of experimental tuberculosis // Problems of tuberculosis and lung diseases: monthly scientific-practical magazine /Russian society of TB (M). - 2005. - N11. - P.44-47; Pat No.2203081 RF Drug iSlate for the prevention and treatment of tuberculosis and how to obtain it./ Lesiovskaja E.E. and others}.

The technical effect of the invention is an antibacterial drug LICHEN-M, characterized by an increased activity against the AI pathogens first of all, mycobacteria (tubercle Bacillus).

The effect is achieved by the fact that the use of mechanochemical treatment of lichen raw material in the presence of alkali leads to the transfer of water-insoluble flavonoids group usanovich and other lichen acids in the soluble state.

The essence of the invention lies in the fact that preextraction processing of dry thalli of lichens using mechanochemical technology with the addition of dry alkali can allocate more full group PVAD due to poorly soluble in water and water-alcohol mixtures of aromatic phenols (Fig.) in the well-soluble reaction. This ensures maximum extraction of all the structural spectrum of active substances, which also does not allow to form the reaction of microbial resistance to this antibiotic complex.

The invention can be implemented as follows.

The dried thallus of lichens of the genus Cladina {Cladonid} is subjected to mechanochemical treatment in a ball mill (for example, AGO-2) in the presence of solid alkali sodium at 1500 rpm Obtained dry mixture insist on 40%of water-alcohol mixture within 7 days, the solution is separated from the precipitate by centrifugation (filtered under pressure) and neutralized to a pH of 6.9-7.0 and citric acid.

Antibacterial the Noah effect of the drug LICHEN-M against opportunistic, pathogens and Mycobacterium tuberculosis (MBT) is proved in experiments on cultures of bacterial strains and outbred white mice by standard methods.

Investigated the influence

complex lichen PVAD on cultures of bacterial strains eight conditionally pathogenic and pathogenic microorganisms;

- extract of the thalli of lichens on the biological properties of the ILO in vitro, including with drug resistance to anti-TB drugs (PTP);

complex lichen PVAD on the course of experimental tuberculosis in outbred white mice.

Comparative study of antibacterial action of 40% aqueous-alcoholic extract of the thalli of lichens without prior mechanochemical processing (extract # 1) and drug LICHEN-M (table 1).

Shows the full lytic ability of the drug LICHEN-M in relation to eight of conditionally pathogenic and pathogenic bacterial strains, including Staphylococus aureus, Klebsiella pneumoniae, hemolytic E. coli and other (table 1), whereas the extract No. 1 showed high efficacy only against Proteus vulgaris. In other cases, or barely noticeable attempt to lysis, or the microorganisms were visualized in part.

In order to study the antibacterial activities of the extracts of lichens No. 1 and drug LICHEN-M the and biological properties of the ILO conducted a pilot study on the clinical strains office No. 691, sensitive to PTP, and No. 742 resistant to streptomycin at a concentration of 25 μg/ml, isoniazid concentration of 1 µg/ml, rifampicin 80 ág/ml (table 2 and 3).

Determination of activity of antibacterial action of the tested lichen extracts was performed by the method of serial dilutions on solid nutrient media in a ratio of from 1:1 to 1:512. As the nutrient medium used traditional nutritious egg medium for growing office - Finn-2 (f-2). The effectiveness of antibacterial action of lichen extracts was determined by the appearance of the primary, intensive and massive growth of the cultures of the office.

Under the action of extract No. 1 on the clinical strains No. 691 and 742 in dilutions 1:1, 1:2 and 1:4 reported no growth of mycobacteria in the environment (bactericidal effect). In a dilution of 1:8 is the delay in initial and intensive growth compared with the control culture. A dilution of 1:16 has on the office moderate bacteriostatic effect (table 2 and 3).

Drug LICHEN-M in dilutions 1:1, 1:2 and 1:4 also has a bactericidal effect on the office of clinical strain No. 691 (table 4). A dilution of 1:8 bacteriostatic action. Weak bacteriostatic effect dilution of 1:16 and 1:32 with delay in initial and intensive growth for 6 days and increased to 100 CFU compared with the control. Bactericidal action is e drug LICHEN-m on the clinical strain No. 742 was observed at dilutions 1:1, 1:2, 1:4 and 1:8. Starting with a dilution of 1:16, there is a delay in initial and intensive growth of the office by 7 and 6 days, respectively, with poor growth of up to 20 KOE. Therefore, the drug LICHEN-M in a dilution of 1:16 has a marked inhibitory effect on the office (table 5).

Determination of specific activity of the extracts on the course of experimental tuberculosis was carried out on 18 outbred white mice weighing 13-16 g, obtained from the vivarium of the Yakut Republican veterinary testing laboratories. The mice were infected with introduction into the skin of the back suspension (0.1 mg bacterial mass in 0.5 ml saline) three-week culture of clinical MBT strain No. 238 multidrug resistance. Study the extracts were injected into mice inside from the day of their infection.

All experimental animals were divided into following groups of 6 animals in each group: group 1 - infected animals (infection control) no treatment; group 2 - infected animals receiving the extract of the lichen No. 1 in a dilution of 1:8; 3rd group - infected animals receiving the drug LICHEN-M in a dilution of 1:8. The duration of the experiment was 2.5 months, surviving to this time the animals were killed.

The main indicators of resistance of the animal to the TB is the duration of survival after inficon the cation and the General condition of the animals.

Mortality of mice of the 1st group (control of infection), not treated, amounted for the period of the experiment 100%. The death of the mice was observed in the period from 20 to 73 days, the average life expectancy was 39 days, which indicates the high virulence of the used culture of the office. Total body weight loss in this group was 32%. In mice the 2nd group mortality for the period of the experiment was 50%, with an average life expectancy of 51.5 days. Total body weight loss in this group was 8%. In mice 3rd group receiving the drug LICHEN-M, mortality was during the period of the experiment 16.6% (in the course of the experiment died 1 mouse in the 73rd day of the experiment). The total body weight of the animals in this group increased by 2.5 g (16-19%).

Therefore, demonstrated very high efficacy MOSS-M in relation to conditionally pathogenic and pathogenic bacterial strains, including Staphylococus aureus, Klebsiella pneumoniae, hemolytic E. coli, Salmonella enteridis and others, even their drug-resistant forms, as well as against mycobacterial strains sensitive and resistant to anti-TB drugs. Set high antimycobacterial drug activity MOSS-M when used in the treatment of experimental tuberculosis in vivo led to a sharp reduction in severity of infection in mice, INF is different office.

A method of producing a drug that has anti-TB activity, characterized in that the dried thallus of the lichen genus Cladina (Cladonia) is treated mechanically in the presence of solid alkali sodium obtained dry mixture is soaked in a 40%water-alcohol mixture within 7 days, the solution is separated from the precipitate by centrifugation, neutralize citric acid.



 

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