GB842582A - Isolation of tetracycline and/or chlortetracycline from a fermentation broth - Google Patents

Abstract

Tetracycline and/or chlor-tetracycline are extracted from a fermentation broth containing same by (1) acidifying mash to a pH of 0,5 to 2,5 and preferably 1,3 to 1,4 to solubilise the antibiotic (2) adjusting the calcium and magnesium ion content of the mash to between 10 and 45 milligrams per gram of antibiotic in the mash (3) adding thereto a quaternary ammonium compound having the formula: <FORM:0842582/IV(b)/1> wherein R1 is 1 to 4 carbon alkyl or benzyl, R2 is an aliphatic chain of at least 8 carbon atoms, R3 and R4 are 1 to 4 C alkyl or R1 and R4 when taken together represent a divalent carbon chain of 2 to 5 carbon atoms (4) adjusting the pH of the mash to 5,5 to 11 and especially 8,4 to 8,6 and (5) adding a water-immiscible polar organic solvent to extract the antibiotics from the treated mash. Acidification (1) is by a strong mineral acid such as hydrochloric sulphuric or phosphoric acid. Adjustment of calcium and magnesium ion content (2) is by the addition of oxalic acid or ammonium oxalate followed by stirring. The amount of quaternary ammonium compound added in step (3) is 1/2 to 3 moles of such compound per mole of antibiotic. The organic solvent (5) is used in quantities of at least 10% and up to 50% of the mash. The preferred solvent is a methyl alkyl ketone such as methyl butyl ketone and methyl isobutyl ketone but butanol may be used. The quaternary ammonium compounds specified are the "Arquads" (Registered Trade Mark) which are primarily alkyltrimethylammonium chlorides of formula R-N(CH3)3Cl wherein R is octyl, decyl, dodecyl, tetradecyl, hexadecyl and octadecyl and onamine compounds of formula: <FORM:0842582/IV(b)/2> After the addition of the organic solvent, the mash is stirred with a filter acid, the organic solvent layer separated from the filtrate and treated to recover the antibiotic as the mineral acid salt or as the free base. Apart from direct acidification, the processes of Specifications 821,309 and 835,468 may be used for the recovery of tetracycline. In the case of chlortetracycline, it is desirable that the colour be improved by adjusting the organic solvent extract to pH 1 to 4 and preferably pH 1,8 by means of sulphuric acid in the presence of water, adding sodium hydrosulphite (or other reducing agent such as sulphur dioxide and sodium sulphite) at a level of 0,3 to 0,6 grms per 100 millilitres, acidifying to pH 0,5 with hydrochloric acid, and then adding sodium chloride to provide sufficient chloride ions to compensate for the sulphuric acid used.