GB718021A - A new antibiotic and a process of obtaining the same from an oxytetracycline fermentation broth - Google Patents

Abstract

An antifungal antibiotic P.A. 85 is obtained from a fermentation broth produced by the cultivation of a Terramycin-producing-strain of Streptomyces rimosus according to Specification 684,417, by first separating the Terramycin (oxytetracycline) and then subjecting the residual material from such separation to a concentration procedure. P.A.85 is present in both the filtered fermentation broth and in the mycelium. It may be recovered from an alcohol, e.g. butanol extract of the mycelium, or from the filtered fermentation broth by adjusting to a basic pH and (a) extracting with wet butanol, removing the oxytetracycline by a mineral acid, e.g. hydrochloric wash, and treating the butanol residue with petroleum ether to concentrate the P.A.85 in the aqueous layer, (b) precipitating the oxytetracycline as a bivalent metal complex according to the method of Specification 718,020 and (i) spray drying or otherwise concentrating the residue or (ii) adsorbing the P.A.85 on, e.g., activated charcoal and thereafter extracting with a solvent such as 1 to 4 C alcohol, pyridine or other organic base preferably containing water. The antibiotic is purified by (a) washing butanol solutions with dilute acids and alkalies and then treating with activated carbon, (b) treating solutions with ion-exchange resins, e.g. "Amberlites" (Registered Trade Mark), zeolites, sulphonated coals and sulphonated humic acid, (c) dialysis, (d) precipitation from aqueous solutions by water-soluble inorganic salts, e.g. sodium chloride and ammonium sulphate. Crystals of P.A. 85 are obtained from methanol solutions containing an organic amine sulphate, e.g. triethylamine sulphate, by the addition of acetone. This may be recrystallized from methanol and water. P.A. 85 is active against a variety of pathogenic fungi; it is acidic forming salts; it is soluble in 1 to 4 carbon alcohols, slightly soluble in water and acetone; the hydrated crystals melt at 149-153 DEG C.; it has characteristic ultra-violet and infra-red absorption spectra; [a ]D + 74 DEG in 1 per cent methanol; contains the elements C, H, O and nitrogen only.