PROCESS FOR PREPARING A NOVEL ANTIBIOTIC SUBSTANCE AND SALTS THEREOF

1,161,278. An antibiotic, adriamycin. SOC. FARMACEUTICI ITALIA. 16 April, 1968 [18 April, 1967],No. 17819/68. Heading C2A. The invention comprises an anti-tumour, antibacterial antibiotic, adriamycin having the formula its aglycone, adriamycinone, of formula and its salts with inorganic and organic acids. Adriamycin is produced by cultivating Streptomyces peucetius var. caesius I.M.I. 131.502 (I.M.R.U. 3920). F.I. 106 (Farmitalia microbiological collection) in a liquid nutrient medium under aerobic conditions. Adriamycin may be isolated from the whole broth, the separated mycelium or clarified broth. The mycelium is extracted with acidified acetone, neutralized, acetone removed in vacuo, the aqueous residue adjusted to pH 3À0, extracted with chloroform to remove impurities, adjusted to pH 8À6, extracted with chloroform/ methanol (9:1) and precipitated from the extract by the addition of diethyl ether. The clarified broth is extracted with chloroformmethanol (9: 1) at pH 8.6, re-extracted with 0À01 N HCI, the acid extract adjusted to pH 8À6 and the chloroform-methanol extraction repeated, the crude being recovered as above. Alternatively, the antibiotic may be adsorbed on a cationic carboxylic exchange resin in acid form, and eluted with methanolic sodium chloride. Adriamycin is purified by chromatography on cellulose powder buffered with M/15 phosphate at pH 5À4 and eluted with propanol-ethyl acetate-water (7: 1: 2). Active fractions are extracted with chloroform at pH 8À6 and adriamycin HCl is precipitated by the addition of HCl in methanol. It may be recrystallized from ethanol. Adriamycinone is obtained by the acid hydrolysis of adriamycin HCl e.g. heating with 0À5N HCl for one hour at 100‹ C. Adriamycin forms salts with H 2 SO 4 , acetic, propionic, valeric, palmitic, oleic, citric, succinic, mandelic, glutamic and pantothenic acids. Pharmaceutical compositions for oral, parenteral or topical administration comprise the antibiotic adriamycin, its aglycone adriamycinone or its salt, alone or in admixture, together with a carrier.