GB1180701A - Process for Purifying Tetracycline Antibiotics with Phosphate Salts - Google Patents

Abstract

1,180,701. Purification of tetracycline antibiotics. CHAS. PFIZER & CO. Inc. 24 April, 1968 [23 June, 1967], No. 19497/68. Heading C2A. A tetracycline antibiotic is recovered from an impure mixture thereof containing metallic calcium, magnesium and/or ferric cations by (a) forming a solution by adjusting to a pH of 0À5 to 2À5 a mixture of water, a completely water-miscible organic solvent in the ratio of 0À2 to 3À0 (based on parts by volume of the organic solvent to water) and said impure mixture, (b) adding thereto a sodium, potassium or ammonium salt of orthophosphoric acid, metaphosphoric acid, pyrophosphoric acid or polyphosphoric acid, in an amount of at least 2 millimoles of phosphate salt per million units of tetracycline antibiotic activity in said solution, and (c) maintaining the pH of the resulting mixture at a value of from 2À5 to 7 and recovering the precipitated antibiotic. Optionally, 1 to 6 millimoles of urea for each million units of antibiotic may be added to the solution of step (a). Preferably, the urea and phosphate are dissolved in water and the solution added to the organic solvent solution of the antibiotic. The preferred organic solvent is methanol, but diethylene glycol or ethylene glycol monomethyl ether may be used. The tetracycline antibiotic is one produced by fermentation and includes tetracycline, chlortetracycline, oxytetracycline, 7 - chloro - 6 - demethyltetracycline, 7 - bromo - 6 - demethyltetracycline, bromtetracycline and 6 - demethyltetracycline; also tetracycline produced by the hydrogenation of fermentation-produced chlortetracycline.