| 摘要 |
Disclosed is a novel and improved process for the isolation of clavulanic acid and of pharmaceutically acceptable salts thereof such as potassium clavulanate from the aqueous fermentation broth of Streptomyces sp. P 6621 FERM P 2804, wherein from the fermentation broth the mycelium, a major part of proteins and other suspended solid particles are removed by microfiltration at a pH value of the medium between 5.8 and 6.2 and at a temperature between about 20.degree.C and 40.degree.C, the purified broth (the aqueous phase) is optionally additionally purified by ultrafiltration, and the thus purified broth is concentrated by reverse osmosis, then it is directly extracted in a countercurrent in centrifugal extractors with a water-immiscible organic solvent at a pH value of the medium between 1 and 3, whereat the still remaining proteins are simultaneously removed, from the obtained organic phase the water-soluble impurities are removed by washing the organic phase with water, the organic phase is dried in vacuo in a rectification column to a water content under 0.1 vol % and then concentrated by evaporation, decolourized by a treatment with active carbon and then the clavulanic acid present in the dry organic phase, most suitably in the ethyl acetate phase, is isolated and purified by a reaction with N,N'-diisopropylethylenediamine at a temperature of about room temperature to the intermediary N,N'-diisopropylethylenediammonium diclavulanate, which is isolated and then reacted with potassium 2-ethyl hexanoate in isopropanol to yield potassium salt of clavulanic acid having high purity.
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