US 12,303,573 B2
Formulation of contrast media and process of preparation thereof
Stephan Holzschuh, Haan (DE); Thomas Frenzel, Berlin (DE); Gregor Jost, Berlin (DE); Jessica Lohrke, Berlin (DE); Wolfgang Ebert, Krefeld (DE); Thomas Brumby, Berlin (DE); and Wolfgang Halfbrodt, Berlin (DE)
Assigned to BAYER AKTIENGESELLSCHAFT, Leverkusen (DE); and BAYER PHARMA AKTIENGESELLSCHAFT, Berlin (DE)
Filed by BAYER AKTIENGESELLSCHAFT, Leverkusen (DE); and BAYER PHARMA AKTIENGESELLSCHAFT, Berlin (DE)
Filed on Mar. 26, 2024, as Appl. No. 18/617,245.
Application 18/617,245 is a continuation of application No. 17/295,647, granted, now 11,944,690, previously published as PCT/EP2019/082117, filed on Nov. 21, 2019.
Claims priority of application No. 18208090 (EP), filed on Nov. 23, 2018.
Prior Publication US 2024/0252690 A1, Aug. 1, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 49/10 (2006.01); A61K 49/08 (2006.01); A61K 49/12 (2006.01)
CPC A61K 49/108 (2013.01) [A61K 49/085 (2013.01); A61K 49/124 (2013.01)] 14 Claims
 
1. A liquid pharmaceutical formulation comprising:
a DO3A-derived tetra-chelate having a general formula selected from the chelates of formulae (I-a), (I-b), and (I-c):

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
or a stereoisomer, a tautomer or a salt thereof, or a mixture of same in a range of from 70 to 700 mmol of Gd3+ ion/L;
a compound capable of forming a chelate with a free gadolinium metal ion Gd3+ comprising Ca-BT-DO3A (Calcobutrol) in a range of 0.002% to 5% mol/mol (inclusive) measured as a proportion relative to a total Gd3+ concentration in the liquid pharmaceutical formulation;
a buffer in the form of 10.0 mmol/L Trometamol (TRIS, 2-amino-2-(hydroxymethyl) propane-1,3-diol);
an isotonicity agent in the form of NaCl;
a pH adjusting agent in the form of 0.1 N HCI (aq); and
a pharmaceutically acceptable solvent in the form of water.