(57) Abstract:

A new antibacterial agent in the form of tablets for buccal injection on the basis of gramicidin S. the Proposed structure of the auxiliary components (methylcellulose, and others) improve the biopharmaceutical properties of the composition and improves its bioavailability. The invention expands the Arsenal of the declared destination.

The invention relates to the field of pharmaceutical industry and relates to pelletized forms of antibiotics.

The most common diseases of social significance related infectious diseases of the oral cavity and pharynx. Despite the significant potential funds available in modern medicine to combat these diseases, the problem still remains. This is largely due to both the high incidence and nature of microorganisms that constantly mutate and form resistant strains. The resistance of microorganisms to antibacterial agents is an important issue that determines the correct choice of treatment for the patient. In the first years after open the Lin remained sensitive already no more than 20-30%. The growth of resistant forms related to the fact that in populations of bacteria are constantly emerging antibiotic-resistant mutants possessing virulence and receiving spread predominantly in cases where sensitive forms overwhelmed by the antibiotic. From a population genetic point of view, this process is reversible. Therefore, when the temporary withdrawal of this antibiotic from the Arsenal of therapeutic tools-resistant microbes in the populations of the newly replaced sensitive forms that multiply at a faster pace.

Currently the main antibacterial drugs used for the treatment of this group of diseases, remain antibiotics. In the practice of medicine introduced a new generation of antibiotics. At the same time, there is a tendency, along with the search for new pharmacological tools to maximize the potential of already known means.

Such tools include gramicidin S, one of the first native of antibiotics, first obtained I. F. Gause and M, Brazhnikova in 1942

Gramicidin belongs to the group of polypeptide antibiotics, broad-spectrum, bacteriostatic and bactericidal effects ciruits spore Bacillus Bacillus brevis var. G.-B.

Gramicidin is intended for use for acute pharyngitis, aphthous lesions of the oral mucosa and stomatitis, gingivitis, tonsillitis, etc.

Chemical name: Cyclic (L-leucyl-D-i.e. phenylalanyl-L-prolyl-L-poured-L-Omnitel-L-leucyl-D-i.e. phenylalanyl-L-prolyl-L-poured-L-Omnitel).

Brutto-formula: C60H92N12010

Code CAS: 113-73-5

The implementation mechanism of the bactericidal effect of gramicidin associated with increased permeability of the microbial cell membrane for inorganic cations by forming a network of channels in the lipid membrane structures, which results in osmotic fragility of the cells. Is intended only for local use, because when parenteral develops generalized hemolysis and phlebitis.

In the restricted microflora retained sensitivity to this antibiotic.

Therefore, the development of improved forms of gramicidin a is of interest to researchers in the field of pharmacy.

It is known the use of gramicidin a in the form of a 2% aqueous alcohol solution to rinse (M. A. Klyuev. Medicinal product. - M.: Russian book, 1993, S. 133). The use of antibiotic in view of the foams but, has a very bitter taste and is often the cause of nausea.

It is known the use of gramicidin in the form of tablets for dissolution in the oral cavity based on gelatin (patent GB 1060258, 01.03.1967). Lozenges during storage quickly lose their effectiveness, and it does not solve the problem of eliminating unpleasant taste.

Known tableted form of gramicidin for the treatment of angina, containing ascorbic acid, tannin, sugar, starch and talc (L., Peretz, etc.. Tablets of gramicidin with activators and their use in the treatment of angina and the prevention of scarlet fever. Increased activity of antibiotics, sulfonamides, and blood serum. Sat. articles, Sverdlovsk, 1957, S. 195-198). Tablets have a low dose of antibiotic and require frequent application.

Also known tableted form of gramicidin containing additional dry extracts of marshmallow and licorice, menthol, as well as auxiliary substances - polyethylene oxide, sugar, dairy, refined sugar, and calcium stearate (RF patent 2160088 C1, 10.12.2000). For obtaining this form of dry marshmallow extract is mixed with part of the milk sugar and refined sugar, moistened with a solution of gramicidin in which dissolved menthol, the mass is dried and granularit; separately mixing extra is l, optivault and pressed tablets. Tablets are additional expectorant and anti-inflammatory effect. However, often cause side effects such as nausea, caused by specific taste, and intolerance.

The objective of the invention is to provide a dosage form, devoid of the above disadvantages.

The problem is solved by creating a tablet form of gramicidin a, containing the following ingredients in wt.%:

Gramicidin S - 0,2-0,4

Sugar - 48,1-48,4

Milk sugar - 48,1-48,4

Methylcellulose, MC-100 - 0,2-0,4

Calcium stearate - 2,8-3

The method of obtaining the proposed tablets gramicidin is as follows.

Refined sugar in the form of powder and the lactose in a ratio of 1:1 is sifted through a sieve 38, mix, moisten the mixture solutions of 5% aqueous solution of methylcellulose and alcohol solution of gramicidin S. the Wetted mass granularit through a sieve with D-1.2 mm, air-dried or kiln drying at a temperature not exceeding 40oWith up to a moisture content of 1.5-2.5%. After drying, the mass is passed through a granulator with a hole diameter of the drum 1-1,2 mm Obtained granulate optivault the calcium stearate and tabletirujut.

The combination of refined sugar in the form of powder and lactose of 1:1 is optimal taste masking, which at the same time is not cloying, as in the use of synthetic sweeteners such as saccharin, or licorice in the famous tablets.

The introduction of methyl cellulose provides a more lasting effect compared with polyethylene oxide and a higher bioavailability than the well-known tablets.

The invention can be illustrated by the following example:

Tablets of gramicidin a mass of 0.6 g contains, wt%:

Gramicidin - 0,28

Powdered sugar - 48,3

Milk sugar - 48,3

Methylcellulose, MC-100 - 0,23

Calcium stearate - 2,89

Biopharmaceutical properties of the resulting tablets was investigated by the method of diffusion of their alcohol extract in agar when comparing zones of growth inhibition of the test microbe Bac.subtilis and mortar working standard sample of gramicidin. The obtained data show a higher activity of the offered tablets. Zone of inhibition of growth of test microbes on average 14% more than the standard.

Developed tablets can be successfully applied as antimicrobial agents for the treatment of diseases service of the substance, characterized in that it contains as excipients powdered sugar and milk sugar at a ratio of 1:1, methylcellulose and calcium stearate in the following ratio, wt. %:

Gramicidin S - 0,2-0,4

Sugar - 48,1-48,4

Milk sugar - 48,1-48,4

Methyl cellulose MC-100 - 0,2-0,4

Calcium stearate - 2,8-3rd


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