• Patent Title: Stable pharmaceutical composition containing folates
  • Application No.: US14787980
    Application Date: 2014-04-30
  • Publication No.: US09642853B2
    Publication Date: 2017-05-09
  • Inventor: Martin Ulmann
  • Applicant: APROFOL AG
  • Applicant Address: CH Appenzell, Steinegg
  • Assignee: APROFOL AG
  • Current Assignee: APROFOL AG
  • Current Assignee Address: CH Appenzell, Steinegg
  • Agency: RatnerPrestia
  • Priority: EP13002299 20130430
  • International Application: PCT/EP2014/001153 WO 20140430
  • International Announcement: WO2014/177274 WO 20141106
  • Main IPC: A61K31/519
  • IPC: A61K31/519 A61K9/00 A61K47/12 A61K47/24 A61K9/08
Stable pharmaceutical composition containing folates
Abstract:
The administration of leucovorin as well as other active, reduced folates is useful as an antidote to drugs which act as folic acid antagonists and in combination chemotherapy with 5-FU. The most often used calcium salts of the folates have a low solubility in water and form almost insoluble degradation products. Therefore, aqueous solutions are unstable and precipitates result. Precipitates in injectable products present an unacceptable safety risk to patients. Stable high strength pharmaceutical aqueous compositions are formed containing calcium salts, magnesium or zinc salts of the reduced folates leucovorin, (6R,S)-tetrahydrofolic acid, (6S)-tetrahydrofolic acid, 5,10-methylene-(6R,S)-tetrahydrofolate, 5,10-methylene-(6R)-tetrahydrofolate, 5-methyl-(6R,S)-tetrahydrofolate or 5-methyl-(6S)-tetrahydrofolate and one or more of the compounds sodium gluconate, potassium gluconate, glycerophosphate disodium salt or glycerophosphate dipotassium salt.
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