Process for the production of clavulanic acid

C - Chemistry – Metallurgy – 12 – P

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C12P 17/18 (2006.01)

Patent

CA 2669931

The present invention relates to a process for preparation of a pharmaceutically acceptable metal salt of clavulanic acid comprising the steps of (a) fermenting of a microorganism capable of producing and excreting the clavulanic acid into the broth; (b) removing biomass and other solid material from the clavulanic acid containing fermentation broth obtained in step (a); (c) acidifying the solution obtained after step (b) to a pH between 1 and 3 and extracting the acidified solution with a partly or fully water-immiscible solvent and separating the clavulanic acid containing extract; (d) mixing the clavulanic acid containing extract obtained in step (c) with a metal donor and at least one additional cosolvent to result in an insoluble, preferably crystalline metal clavulanate salt with a yield of at least 80%; and (e) separating the insoluble, preferably crystalline, metal clavulanate salt from the mixture obtained in step (d).

La présente invention concerne un procédé de préparation d'un sel métallique pharmaceutiquement acceptable d'acide clavulanique, qui consiste à> (a) fermenter un micro-organisme capable de produire et d'excréter l'acide clavulanique dans le bouillon; (b) éliminer la biomasse et toute autre matière solide du bouillon de fermentation contenant l'acide clavulanique obtenu en (a); (c) acidifier la solution obtenue en (b) à un pH situé entre 1 et 3 et extraire la solution acidifiée avec un solvant partiellement ou entièrement immiscible dans l'eau et séparer l'extrait contenant l'acide clavulanique; (d) mélanger l'extrait contenant l'acide clavulanique obtenu en (c) avec au moins un donneur m;tallique et un co-solvant additionnel de façon à donner un sel métallique de clavulanate insoluble et de préférence cristallin avec un rendement d'au moins 80 %; et (e) séparer le sel métallique de clavulanate insoluble et de préférence cristallin du mélange obtenu en (d).

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