发明名称 Process for the preparation of the stable, amorphous calcium salt of (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid
摘要 <p>(6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid calcium salt aqueous solution production involves methylating (6S)-5,6,7,8-tetrahydrofolic acid with a part of the corresponding (6R)-diastereoisomer in the range of 4-8 wt.% in water. Calcium chloride is added into the assigned quantity of tetrahydrofuran to obtain 0.70-0.82 equivalent of the methylated reaction mixture. The calcium salt of the (6RS)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid is selectively crystallized and separated from the obtained aqueous solution. The obtained aqueous solution of the calcium salt of the (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid has less than or equal to 2.0 wt.% of the corresponding (6R)-diastereoisomer. Independent claims are included for: (1) a method for producing stable, crystalline (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid for use as an active component in a dietary supplement or in a medicine, for treating or suppression of human or animal tumors, and for synergistic influence of cancer suppressing compound, reducing toxicity of cancer suppressing compound, and protecting human or animal cells, which involves adding acetic acid or a sulfonic acid to an aqueous solution of the calcium salt of (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid with a portion of the corresponding (6R)-diastereoisomer of less than or equal to two weight percent; and (2) a method for producing stabilized, amorphous calcium salt of (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid, which involves suspending manufactured (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid in water, adding a solution of sodium hydroxide to this suspension, adding calcium chloride to the manufactured solution.</p>
申请公布号 EP2354142(A1) 申请公布日期 2011.08.10
申请号 EP20110003589 申请日期 2008.05.29
申请人 CERBIOS-PHARMA S.A. 发明人 MANZOTTI, RAFFAELLA;MOROSOLI, MORENO
分类号 C07D475/04 主分类号 C07D475/04
代理机构 代理人
主权项
地址