Stable pharmaceutical compositions of 5,10-methylene tetrahydrofolate

摘要

This invention relates to stable pharmaceutical compositions of 5,10-methylene-(6R)-, -(65)- or -(6R,S)-tetrahydrofolate (MTHF), by adjusting to a basic pH and the simultaneous use of citrate. Stabilisation is effected even in the absence of a reducing agent. The present invention is particularly suitable for producing lyophilisation solutions and lyophilisates or dry powders and dry mixtures, since the stable MTHF solutions can be used in high concentrations for filling corresponding vessels such as vials, ampoules, etc. The lyophilisates have a surprisingly long shelf life and are surprisingly stable. They can be reconstituted without problems by adding water or aqueous solutions, and the final clear injection solutions again exhibit excellent stability properties. Moreover, the present invention even makes it possible to prepare difficultly soluble calcium 15 or acidic salts of MTHF in high concentrations and as physiologically compatible isotonic solutions.

主权项

1. A stable pharmaceutical composition of 5,10-methylene-(6R)-, -(6S)-or -(6R,S)-tetrahydrofolate, comprising 5,10-methylene-(6R)-, -(6S) -or -(6R,S)-tetrahydrofolic acid or a pharmaceutically acceptable salt of 5,10-methylene-(6R)-, -(6S)-or -(6R,S)-tetrahydrofolic acid and citrate, and has a pH of 7.5 to 10.5.