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    • 2. 发明申请
    • PROCESS FOR PREPARING A PHARMACEUTICAL FORMULATION OF CONTRAST AGENTS
    • 制备药物制剂的方法
    • WO2009103744A3
    • 2009-12-17
    • PCT/EP2009051937
    • 2009-02-18
    • GUERBET SAMEYER DOMINIQUECOROT CLAIREPORT MARCBARBOTIN VINCENTBONNEMAIN BRUNO
    • MEYER DOMINIQUECOROT CLAIREPORT MARCBARBOTIN VINCENTBONNEMAIN BRUNO
    • A61K49/06
    • A61K49/108A61K9/0019A61K31/28A61K45/06A61K47/18A61K49/106G01N33/15
    • The invention relates to a process for preparing a liquid pharmaceutical formulation containing a complex of macrocyclic chelate with a lanthanide and a mol/mol amount offree macrocyclic chelate of between 0.002% and 0.4%, advantageously between 0.02% and 0.3% and very advantageously between 0.025% and 0.25%, the macrocyclic chelate advantageously being chosen from DOTA, NOTA, DOTAGA, DO3A, BT-DO3A, HP-DO3A and PCTA, and is preferably DOTA, the said process comprising the following successive steps: b) preparation of a liquid pharmaceutical composition containing, firstly, the complex of macrocyclic chelate with a lanthanide, and, secondly, free macrocyclic chelate and/or free lanthanide; c) measurement in the pharmaceutical formulation obtained in step b) of the concentration of free macrocyclic chelate C chl and/or of free lanthanide C lanl; d)adjustmentof C chl and/or of C lanl so as to obtain C chl = C tchl and C lanl = 0, wherein C t chl is the target concentration of free macrocyclic chelate in the final liquid pharmaceuticalformulation.
    • 本发明涉及一种制备液体药物制剂的方法,其含有大环螯合物与镧系元素的复合物和摩尔/摩尔量的大分子螯合物,其含量为0.002%至0.4%,有利地为0.02%至0.3%,非常有利地为0.025 %和0.25%,大环螯合物有利地选自DOTA,NOTA,DOTAGA,DO3A,BT-DO3A,HP-DO3A和PCTA,并且优选为DOTA,所述方法包括以下连续步骤:b)制备液体 药物组合物首先含有大环螯合物与镧系元素的复合物,其次,游离的大环螯合物和/或游离镧​​系元素; c)在步骤b)中获得的药物制剂中测量游离大环螯合物C ch1和/或游离镧​​系元素C lanl的浓度; d)调整C chl和/或C lanl,以获得C chl = C tchl和C lanl = 0,其中C t chl是游离大环螯合物在最终液体药物制剂中的目标浓度。