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filingDate 1995-02-23-04:00^^<http://www.w3.org/2001/XMLSchema#date>
inventor http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_cfa92ce67572a3fe2559d905aee81726
publicationDate 1995-09-08-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber CA-2184619-A1
titleOfInvention Novel process for the isolation of clavulanic acid and of pharmaceutically acceptable salts thereof from the fermentation broth of streptomyces sp. p 6621 ferm p 2804
abstract 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°C and 40°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.
priorityDate 1994-03-02-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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