SU1123697A1 - Method of obtaining liposomal form of antibiotics of streptomycin series - Google Patents

Abstract

METHOD FOR LIPOSOMAL antibiotics streptomycin SERIES by treatment with sodium phosphate buffer, characterized in that in order to increase the incorporation of antibiotic into liposomes, mixed buffer solution streptomycin, lecithin and sodium cholate, injected into the upper portion of column buffer antibiotic solution at a ratio of volumes of solutions antibiotic : micellar solution

Description

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The invention relates to medicine, in particular to a method for producing a new dosage form of streptomycin, which can be used in chemotherapy of tuberculosis.

Streptomycin is widely used in the mass clinical chemotherapy of tuberculosis. It is known that this antibiotic, when administered orally, enters the blood in insignificant amounts, therefore during chemotherapy of tuberculosis, the antibiotic is injected as a solution.

The incorporation of drugs into phospholipid vesicles — liposomes — is one of the ways to reduce the toxicity of drugs.

A method of producing a liposomal form of dihydrostreptomycin (a streptomycin derivative characterized by similar pharmacological and physicochemical properties) by ultrasound treatment is known, and liposomes are prepared from a mixture of lipids: an egg phosphatidylcholine, cholesterol, and phosphatidic acid in a 7: 2: 1 molar ratio. The lipid film is dispersed in 5 ml of sodium phosphate buffer containing dihydrostreptomycin and sonicated. When using this method of producing liposomes, the incorporation of dihydrostreptomycin in liposomes is 70 µg / mg lipid 1.

However, the known method does not provide sufficient inclusion of the antibiotic in liposomes.

The purpose of the invention is to increase the inclusion of an antibiotic in liposomes.

This goal is achieved by the fact that according to the method of obtaining a streptomicin-type antibiotics liposomal form by treating with sodium phosphate buffer, a buffer solution of streptomycin, lecithin and sodium cholate is mixed, an antibiotic buffer solution is introduced into the top of the column at a ratio of antibiotic: micelle solutions A clear solution (4-5): 1 and its gel filtration is carried out on a column with Sephadex G-50.

Example J. A mixed micelle solution is formed from 20 mg of lecithin, 2 ml of a 20 / st streptomycin sulfate solution and 0.2 ml of 20% sodium cholate. Gel filtration is carried out on a Sephadex G-50 medium column (1.6x40 cm) after pre-applying on the column 8 ml of a 20% streptomycin sulfate buffer solution (the ratio of the volumes of the previously applied and mixed micelle solutions is 4: 1). The content of streptomycin in a liposomal preparation is 310 µg / mg lecithin.

The data on the comparative inclusion of antibiotics of the aminoglycoside group in liposomes (relative to the concentrations of antibiotics and lipid in liposome preparations) is presented in the table.

Claims (1)

METHOD FOR PRODUCING A LIPOSOMAL FORM OF ANTIBIOTICS OF A STREPTOMYCIN SERIES by treatment with sodium phosphate buffer, characterized in that, in order to increase the inclusion of an antibiotic in liposomes, a streptomycin, lecithin and sodium cholate buffer solution is mixed, an antibiotic solution is introduced into the upper part of the column with the antibiotic solution : micellar solution (4-5): 1 and gel filtration is carried out on a Sephadex G-50 column. Yu GO Oi ς ©