FIELD: medicine; pharmaceutics.
SUBSTANCE: group of inventions relates to pharmaceutical compositions, particularly compositions containing docetaxel-albumin nanoparticles, drugs based on such compositions, as well as a method for preparing them. Disclosed is a composition containing docetaxel-albumin nanoparticles, which contains docetaxel and acid-denatured albumin; and, alternatively, a composition containing nanoparticles of docetaxel-albumin, which is obtained from docetaxel and acid-denatured albumin; wherein said acid-denatured albumin is obtained by adding cysteine hydrochloride to human serum albumin to bring pH to 3.8–4.7 and subsequent denaturation; and content of sodium caprylate in said albumin is not more than 0.08 mmol/g of protein. Also disclosed are lyophilised powder obtained from any of the above compositions; reconstituted suspension obtained by reconstitution of such lyophilised powder; and a drug prepared from said compositions, a lyophilised powder or a reconstituted suspension. Method of producing said compositions, powder or suspension involves the following steps: (1) dissolving docetaxel in an organic solvent to obtain an organic phase solution; (2) providing a human serum albumin solution and adding cysteine hydrochloride to adjust pH to 3.8–4.7 to obtain a solution of an aqueous phase of acid-denatured albumin, where the sodium caprylate content is not more than 0.08 mmol/g of protein; providing a salt solution selected from sodium chloride, potassium chloride, sodium sulphate and magnesium sulphate; (3) mixing the above solutions of the organic phase, the aqueous phase and the saline solution for loading the drug to form a drug-loaded solution; and (4) dialysis of the drug-loaded solution to obtain a composition containing docetaxel-albumin nanoparticles. Also disclosed is a composition containing docetaxel-albumin nanoparticles obtained using said method, and a medicinal agent based thereon.
EFFECT: use of said albumin, acid-denatured at a certain pH value, and control of sodium caprylate content provide physical and chemical stability of the disclosed compositions and medicinal agents.
22 cl, 7 tbl, 13 ex
