The method of obtaining a tablet form of the drug-probiotic

 

(57) Abstract:

The invention relates to biotechnology, namely the production of biological preparations of probiotics. The production strain B. subtilis 3H cultivated in a nutrient medium and concentrate on nutrient medium providing education dispute, to separate the biomass from the culture medium and concentrated by microfiltration method. The concentrate is mixed with stabilizers, contribute calcium gluconate in an amount of from 1.0 to 10.0 wt.% to make the biomass required physical properties and freeze-dried in magazines. If necessary, you can mix the prepared biomass with a sorbent in a ratio of 1:1 on a dry residue, after which the liquid is separated by filtration and dried microspheres immobilized biomass vacuum drying to a residual moisture content of 8-10%. After drying the biomass is mixed with auxiliary substances in the ratio of 2:1-3:1 and tabletirujut. As auxiliary substances used calcium stearate, talc, and / or starch and / or Aerosil, glucose, milk powder and / or methylcellulose. In the invention receive a tablet form of the drug, easy to use, providing the manifestation of therapeutic and prophylactic properties p is the production of biological preparations of probiotics.

Currently there are a number of biological products from bacteria of the genus Bacillus, inhibit the growth of pathogenic and conditionally pathogenic bacteria: bioperin, backspin, baktisubtil, etc. Their therapeutic efficacy is determined by the complex action of a broad range of metabolites that are able to produce live bacterial cells, bacterial strains included in the preparations.

Study of the mechanism of therapeutic and preventive effects of probiotics on the human body and animals shows that bacteria have the ability to be absorbed from the gastrointestinal (GI) tract into the blood and from there to the lesion, to survive, to produce antibiotics, proteolytic enzymes, and immunomodulators. It was found that after oral administration, in the first minutes through the mucous membranes of the oropharynx, esophagus and stomach approximately 0.1% of the total number of bacteria penetrate into the parenchymatous organs asymptomatic translocation of microorganisms, it lasts 6-8 hours after a single dose of the drug to the elimination of microbial cells from organs, during which the effects of the drug on the body (1).

Antagonistic action of the bacilli of osushestvim, lytic enzymes (2). The high enzymatic activity of the bacilli is positive from the point of view of the enrichment of gastric secretion more, including predigestive enzymes (3, 4). Bacilli not form biofilms, because their adhesive properties are poorly expressed. Their activity is in the lumen of the digestive tract and relates primarily not to the competitive relationship for attachment to the mucosa, and with high antagonistic activity against pathogenic microorganisms, without the antagonistic actions of representatives of normal microflora, which creates conditions for unbeatable recovery autoflora (2).

A method of obtaining the drug "Backspin" on the basis of the strain Bacillus subtilis 3 N (GISC N 248), comprising culturing the strain in a liquid nutrient medium, the separation of biomass from the nutrient medium by ultrafiltration, concentration and freeze drying (5).

The closest analogue of the invention is a therapeutic biological product "Backspin" based antagonistically active strain of B. subtilis 3H, providing for obtaining biomass of strain, mixing it with a protective environment (sharethelove of smesovany and before use, the ampoule is opened, dry biomass is dissolved in a little water and use orally in the form of a solution. Since the strain, which is part of Bactisporin, a strict aerobe, to carry out its vital functions it can only in the upper GI, where aerobic conditions. Therefore reasoned oral use of the drug without putting it in capsules or coatings that are resistant to dissolution in the upper GI tract (oral cavity, esophagus and stomach).

However, the liquid form of the drug "Backspacing requires dilution with water before use, which reduces the ease of use and limits consumer demand. In addition, at the opening of the ampoule, caution is required to prevent glass ampoule in the drug.

The objective of the invention is to develop a method of producing a tablet form of the drug-probiotic designed for the prevention and treatment of gastrointestinal diseases.

The technical result is to obtain a more convenient form of the drug, which can dissolve in the upper GI tract, while maintaining its therapeutic and antagonistic properties.

To achieve specified the production strain C. subtilis 3H cultivated in a nutrient medium, ensuring the formation of a dispute, to separate the biomass from the culture medium and concentrated by microfiltration method, mix it with stabilizers - Saharsa-gelatin medium or lactose, making calcium gluconate in an amount of from 1.0 to 10.0 wt.% to make the biomass required physical properties and freeze-dried in magazines. If necessary, you can mix the prepared biomass with adsorbent (e.g. activated charcoal, cabalonga, lactulose, acetylcellulose, gel, aluminum phosphate) in 1:1 ratio on a dry residue, after which the liquid is separated by filtration and dried microspheres immobilized biomass vacuum drying to a residual moisture content of 8-10%.

After drying the biomass is mixed with auxiliary substances in the ratio of 2:1-3:1 and tabletirujut. As auxiliary substances used calcium stearate, talc, and / or starch and / or Aerosil, glucose, milk powder and / or methylcellulose.

In the invention receive a tablet form of the drug, easy to use, providing the manifestation of therapeutic and prophylactic properties of the drug in the upper GI tract. Used for p is Alicia - 0,5-1,0, talc - 2,5-3,0 and / or starch - 0.5 to 1.0, and(or) Aerosil is 0.5 - 0.8, glucose - 5,0-20,0, milk - 10,0-30,0, and(or) methylcellulose - 0,1-0,5.

The invention is illustrated by the following examples.

Example 1. The strain of B. subtilis 3H cultivated in a liquid nutrient medium that provides the sporulation for 16 hours. The resulting biomass is separated from the nutrient medium and concentrate using microfiltration to the content of microbial cells 100109cells/ml for CCA 10 UNITS. To add biomass regulator on the basis of Saharsa-gelatin medium or lactose and contribute calcium gluconate in the amount of 2.0 wt.%, mix and dried in magazines lyophilic way. After drying the biomass is milled until smooth, add auxiliary substances and tabletirujut in the following ratio, wt. including:

Dry biomass - 50,0

Calcium stearate - 0,8

Talc - 2,5

Glucose - 5,0

Milk powder - 10,0

Methylcellulose - 0,1

The finished tablets are round with a diameter of 0.8-1 cm, with a smooth, hard surface whitish-gray color, sweet taste. The average weight of the tablets is 0,220,02 g with residual moisture not more than 5%. Tablets dissolve in Hcl 0.1 N. and neutral the strain Century subtilis in the number (1-5)(109CFU (colony forming units).

Example 2. The strain of B. subtilis 3H cultivated in a liquid nutrient medium that provides the sporulation for 20 hours. The resulting biomass is separated from the nutrient medium and concentrate using microfiltration to the content of microbial cells (70-100)109cells/ml for CCA 10 UNITS. Concentrate the biomass is mixed with a 10% solution of acetylcellulose (AFC) in an organic solvent in the ratio of biomass:AFC - 1:1 or 2:1 with continuous stirring.

The obtained microspheres are filtered and dried in a vacuum unit under vacuum of 0.01 mm RT.article at a temperature not exceeding 40oC for 10-12 h to a residual moisture content of 8-10%. The number of viable bacteria (CFU) in 0.1 g of finely granulated biomass (5-40)109SOME.

Next, the granules are mixed with auxiliary substances and tabletirujut in the following ratio, wt.h.:

Dry biomass - 100,0

Calcium stearate - 1,0

Talc - 2,0

Starch - 0,5

Aerosil - 0,5

Glucose - 20,0

Milk powder - 26,0

Literature

1. Smirnov centuries, Reznik, S. R., Sorokulova I. B., Kunicka Century A. Discussion questions for the creation and application of bacterial the prospects of using bacteria of the genus Bacillus for the design of new biological products / Antibiotics and chemotherapy. - 1996. -T. 41, N10. -C. 13-15.

3. Slabospitsky, A. T., Pie, Etc., Greenberg, T. A., and others, the Influence of some components of the environment of the bacteria of the genus Bacillus on the processes of synthesis of exopolysaccharides // monitoring and Control of biotechnological processes: proc. Dokl. Vsesojuzn. proc. Bitter, 1985. - S. 33.

4. Slabospitsky, A. T., Krygowska C. S., Reznik, S. R. the Enzymatic activity of the bacilli, promising to be included in the composition of biopreparations // Microbiol. W. -1990. - N2. - S. 9-14.

5. Mikhailova N. A., Kuznetsova, I. N., Cunagin O. C. / Strain of Bacillus subtilis 3H, bearing property of antibiotic resistance // Patent N 2067616 RU, C 12 N 1/20, publ. 10.10.96.

6. Mikhailova N. A., Kuznetsova, I. N., Cunagin O. C. / Therapeutic drug Backspin // Patent N 2130316 EN, A 61 K 35/74, publ. 20.05.99.0

1. The method of producing drug-probiotic-based Bacillus subtilis, comprising culturing in a liquid nutrient medium, the separation of biomass and subsequent concentration, the addition of stabilizers based on sharerelated environment or lactose and drying, characterized in that before drying in biomass also add calcium gluconate in the amount of 1-10 wt. % or mix biomass with sorbent is subjected to drying, make ispolzuut activated carbon, carblog, lactulose, acetylcellulose or gel phosphate of aluminum and after mixing the biomass with a sorbent obtained microspheres are dried by vacuum drying.

3. The method according to p. 1, characterized in that the biomass and excipients take in the ratio of 2: 1-3: 1.

4. The method according to p. 1, characterized in that the auxiliary substances used calcium stearate, talc, and / or starch and / or Aerosil, glucose, milk powder and / or methylcellulose.

 

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