GB647925A - Improvements relating to the extraction and purification of an antibiotic - Google Patents

Abstract

Polymyxin is recovered from a metabolism fluid containing it by treating such fluid, after removal of bacterial cells and any gummy impurities therefrom, at a pH of 4-8 (preferably about 4.5) with one or more sulphated fatty alcohols or esters or a salt or mixture of salts thereof (e.g. a mixture of the sodium salts of sulphated olefines containing 10-18 carbon atoms, the sodium and triethanolamine salts of sulphated lauryl alcohol, sodium dioctyl sulphosuccinate, lauryl sulphate, or a mixture of cetyl and oleyl sulphates). The resulting precipitate is separated by filtration, centrifuging or gravity and freed from water, after which the active fraction thereof may be extracted with a solvent therefor (e.g. methyl, ethyl, n- or iso-propyl, n- or iso-butyl or lauryl alcohol). The polymyxin may be recovered from an ethyl alcohol extract by one of the following methods: (a) the alcohol is evaporated and the residue dissolved in water with the aid of a strong organic base (e.g. benzylamine or cyclohexylamine) with simultaneous addition of sulphuric acid to keep the pH below 9.5, then more sulphuric acid is added to bring the pH to about 2-3, the resulting complex of alkyl sulphate and organic base is extracted with a water-immiscible alcohol (e.g. butyl alcohol), and polymyxin sulphate is recovered from the aqueous phase by freeze-drying; (b) an isopropyl alcohol solution of the polymyxin-alkyl sulphate complex is treated with an isopropyl alcohol solution of a sulphate of a strong organic base to precipitate polymyxin sulphate, or with dry hydrogen chloride to precipitate polymyxin hydrochloride; (c) the ethyl alcohol extract is decomposed with hydrochloric acid, and the solution is poured into excess of acetone to precipitate the polymyxin. The product may be further purified by treatment with activated charcoal or fractional precipitation. According to the Provisional Specification, the process is also applicable to the recovery of other antibiotics of basic nature, such as streptomycin. A further method of recovering polymyxin sulphate from the complex is also described therein. Specification 619,572 is referred to.ALSO:A therapeutic material is prepared by mixing a solution of a salt or complex of polymyxin and a sulphated fatty alcohol or ester with a vehicle such as arachis oil and removing the solvent to leave a suspension of the polymyxin complex in the vehicle. Specified sulphated fatty compounds are sodium and triethanolamine salts of sulphated lauryl alcohol, sodium dioctyl sulphosuccinate, lauryl sulphate, a mixture of cetyl and aleyl sulphates and the sodium salts of sulphated olefins containing 10 to 18 carbon atoms. Suitable solvents are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl and lauryl alcohols. Specification 619,572 is referred to.