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Crystalline levofolinic acid and process for its preparation, uses therof and pharmaceutical compositions comprising the same
专利权人:
GMT FINE CHEMICALS SA
发明人:
PASCAL JEQUIER
申请号:
IL21876412
公开号:
IL218764A
申请日:
2012.03.20
申请国别(地区):
IL
年份:
2015
代理人:
摘要:
The present invention relates to a processfor the preparation of crystalline folinic acid in essentially pure 6S-form, comprising the steps of:- preparing a first aqueous or hydroalcoholic solution, having a pH value higher than 4.5, of a soluble levofolinate salt- forming a second solution, by adding said first solution and a second acid to a batch of water or an hydroalcoholic mixture, containing up to 60% V/V of an alcohol, pre-heated at a temperature comprised between 30 and 60 °C, operating in such a way that the levofolinate salt concentration in the second solution never exceeds 4% m/V, the pH value of the second solution always remains in the range between 3.0 and 4.5, and the temperature of the second solution always remains in the range between 30 and 60 °C- upon completion of the addition of said first solution to said batch of water or hydroalcoholic mixture, stirring the thus formed second solution while the precipitation of levofoliriic acid occurs, maintaining the solution at a temperature between 30 and 60 °C, monitoring the pH and continuously adding said second acid to keep the pH stable, until it is observed that the pH value becomes stable with no need of further addition of said second acid, indicating the end of the precipitation of levofolinic acid- recovering crystalline levofolinic thus formed.
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来源网址:
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