ES382680A1 - New antibiotic b-5050 and production thereof - Google Patents

Abstract

The new antibiotic B-5050, which is produced by aerobically cultivating a new strain of Streptomyces hygroscopicus having the accession number IFO-12995, is a macrolide substance comprising components B-5050-A, B, C, D, E and F and has the following general properties: Melting point 137 to 141 C. molecular weight 880 90 analysis, C=58À14%, H=7À88%, N=1À73% O=32À15 1À0 specific rotation [[alpha]]24 D =-76À4 8 (C=1 in ethanol) no significant U.V. absorption I.R. absorption bands at 3448, 2924, 1736, 1453, 1376, 1295, 1239, 1167, 1081, 1050, 968, 912, 861 and 840 cm-1. and being a basic substance giving positive reactions to the Dragendorf and Erythromycin tests and a negative reaction to the carbomycin test, soluble in alkanols, ketones, chloroform, benzene, ether, ethyl acetate and aqueous acids and insoluble in neutral water and n-hexane. The components A, B, C, D, E and F have the same general properties as the composite antibiotic B-5050 and have individual distinguishing characteristics as follows: Antibiotic B-5050 is isolated from the fermentation broth, preferably after filtering off the mycelium, by rendering alkaline and extracting with a water-immiscible solvent. The mycelium may also be extracted using a water-miscible solvent. The crude solid is prepared by conventional procedures of absorption and elution, solvent extraction and final concentration and precipitation with a non-solvent. The components are separated by fractional chromatography on a column e.g. of silica gel or alumina, developing with a mixture of polar and non-polar solvent and progressively increasing the proportion of the latter whereby the components are successively eluted in their order of affinity for this solvent i.e. B-5050-A, then -B through to -F. Alternatively they may be separated by partition chromatography or liquid-liquid countercurrent distribution, using similar polar/non- polar solvent mixtures. A further method of separation involves extraction of a waterimmiscible solvent solution of the mixture with progressively acidic buffer solutions or elution from a macroreticular non-ionic resin with aqueous methanol. The antibiotic and its components may be converted to their acid addition salts e.g. the hydrochloride, sulphate, tartrate or nicotinate. Pharmaceutical compositions having antibacterial activity comprise antibiotic B-5050 or one or more of its component antibiotics A to F together with a pharmaceutical carrier. They are preferably in a form for topical application e.g. an ointment.