Tetracycline and chlortetracycline complexes

摘要

The invention relates to the production of N.N1-dibenzylethylene-diamine complexes of tetracycline and of chlortetracycline by fermentation of an aqueous culture medium containing assimilable carbohydrates and organic nitrogen as well as mineral salts with any tetracycline or chlortetracycline-producing strain of a species of the genus Streptomyces, especially S. lusitanus CBS 101-A, characterised by the fact that the fermentation is carried out in the presence of a water soluble salt of N.N1-dibenzylethylenediamine, e.g. p the acetate or lactate under submerged aerobic conditions at a temperature of 24 DEG -30 DEG C., whereafter the resulting complexes are recovered as such or as acid addition salts thereof from the culture medium. The complexes may be isolated by adjusting the pH of the acidified and filtered broth to 7-9,5 with ammonia or an alkali or alkaline earth metal hydroxide. In the case of the alkali or alkaline earth metal hydroxides the corresponding dibenzylethylenediamine metal complexes of tetracycline or chlortetracycline are formed. The dibenzylethylenediamine complexes of chlortetracycline or tetracycline are also obtained by (a) adding dibenzylethylene diamine to an already fermented broth which has been acidified and filtered or (b) adding dibenzylethylene diamine to an aqueous solution of tetracycline or chlortetracycline or (c) the tetracycline complex is obtained by hydrogenation of the chlortetracycline complex in the presence of palladium charcoal and a solvent at 1 to 3 kg/cm2 pressure, the mixture being maintained at neutral or slightly alkaline pH by addition of a tertiary amine, e.g. triethylamine. Tetracycline or chlortetracycline are recovered from their respective complexes by adjusting the pH to their respective isolectric points, e.g. with hydrochloric acid in a water-miscible organic solvent, e.g. methoxy ethanol or ethoxy ethanol and adding water to complete precipitation. The tetracycline or chlortetracycline is recovered as an acid addition salt by reacting their respective complexes with an acid, e.g. hydrochloric acid in the presence of an organic solvent, e.g. methanol, ethanol, isopropanol or butanol or a mixture thereof together with methoxy ethanol or ethoxy ethanol. In the presence of sodium chloride the acid addition salt of the complex is formed. By use of these processes tetracycline or chlortetracycline may be recovered from waste mother liquors.ALSO:An animal feed, e.g. soya meal, comprises a supplement of dibenzylethylenediamine chlortetracycline or dibenzylethylenediamine tetracycline, or both (for preparation see Group IV (b)).