Streptomyces sp. Novel method for isolating clavulanic acid and its pharmaceutically acceptable salts from fermentation broth of P6621 FERM P2804

摘要

The present invention removes most of the mycelia, proteins and other suspended solid particles from the fermentation broth by microfiltration in a medium having a pH of 5.8 to 6.2 between about 20 to 40 ° C., and the purified liquid (aqueous layer) is optionally subjected to ultrafiltration. After purification again by concentrating the purified liquid by reverse osmosis, and then directly extracting by reflux in a centrifugal extractor with an organic solvent which is not mixed with water in a medium having a pH of 1 to 3 to remove the remaining protein at the same time Water-soluble impurities are removed by washing the organic layer with water from the obtained organic layer, and the organic layer is dried in a refinery tube under a water content of 0.1% by volume or less under vacuum, concentrated by evaporation, treated with activated carbon, decolorized and dried. The clavulanic acid present in the organic layer is most suitably isolated on ethyl acetate, and at room temperature, N, Reaction with N'-diisopropylethylenediamine to purify with intermediate N, N'-diisopropylethylenediammonium diclabulate, which is isolated and reacted with isopropanol solution of potassium 2-ethyl hexanoate for high purity Streptomyces sp. Characterized by obtaining a clavulanate potassium salt. P 6621 FERM P 2804 relates to a novel and improved method for the isolation of clavulanic acid and pharmaceutically acceptable salts thereof from the aqueous fermentation broth.