GB1132124A - Process for the isolation of tetracycline antibiotics from impure solutions thereof - Google Patents

Abstract

1,132,124. Tungstate complexes of tetracyclines. KRKA TOVARNA ZDRAVIL. 28 April, 1966, No. 18643/66. Heading C2A. Tetracyclines are isolated from fermentation broths freed from mycelium, or other tetracycline containing aqueous solutions, by precipitating the antibiotic as a tungstate complex by treatment at pH 0À5 to 7À0, with tungstic acid or a water-soluble salt thereof in a weight ratio to the antibiotic of from 0À5:1 to 4À0:1, and then dissolving the precipitate by addition of sufficient sodium hydroxide solution to give a final pH of 8À5 to 10À0 and recovering the antibiotic from this solution. The antibiotic is preferably recovered by either (i) addition of HCl to the alkaline solution to bring the pH to about 7À5, and then adding solid ammonium chloride in a ratio by weight with regard to antibiotic of 1:1 to 3:1, treating this solution with a solution of a magnesium or calcium salt, preferably the chloride, to give a ratio of 1:1 to 1: 4 to the antibiotic, and bringing the pH to 8À0 to 8À2, when the Ca or Mg salt of the tetracycline is precipitated; or (ii) by passage of the alkaline solution first through a column of cation-exchange resin, which takes up the antibiotic, eluting the column with ammonium hydroxide, and then passing the eluate through an anion-exchange resin column, when the antibiotic crystallizes from the solution obtained, after suitable concentration. The tungstic acid or tungstate may be recovered from appropriate stages in the purification by addition of cone. hydrochloric acid, which precipitates the tungstic acid; the latter may be re-employed in the inventive process. Tungstic acid salts employed are ammonium metatungstate and paratungstate, potassium orthotungstate, metatungstate and paratungstate, sodium orthotungstate and paratungstate, and cadmium borotungstate; phosphotungstic acid may also be used.