COMPOSITION OF CONTRAST AGENTS AND METHOD OF ITS OBTAINING Russian patent published in 2024 - IPC C07F5/00 C07D487/22 A61K31/555 A61K49/10 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a liquid pharmaceutical composition for the manufacture of magnetic resonance imaging contrast agents containing a DO3A-derived tetrachelate selected from the chelates of formulas (I-a), (I-b) and (I-c) or a salt thereof, or a mixture thereof. The said composition contains a pharmaceutically acceptable solvent and optionally contains a buffer and at least one compound capable of chelating with a free paramagnetic metal ion Gd³⁺, wherein the said compound is Ca-BT-DO3A (Calcobutrol), preferably ranging from 0.002% to 5% mol/mol (inclusive), measured as a fraction of the total paramagnetic metal ion concentration of the formulation, and wherein the DO3A-derived tetrachelate has a formulation concentration ranging from 60 to 750 mmol paramagnetic metal ion/L (inclusive). The invention also relates to a method of obtaining the specified liquid pharmaceutical composition, to a method of visualizing the entire body of an individual or part of an organism. Besides, the invention relates to a liquid pharmaceutical composition for the manufacture of contrast agents for magnetic resonance imaging, containing a DO3A-derived tetrachelate of general formula (I), in which R¹ is as specified in the claims, and wherein the said composition contains a substoichiometric chelate, selected from chelates of formula Gd₃-II-a, Gd₂-II-a and Gd-II-a and a tetraligand of formula (II-a). The invention also relates to a tetrachelate obtained from DO3A with substoichiometric amounts of gadolinium ions of the formula Gd₃-II-a, Gd₂-II-a and Gd-II-a and the use of these tetrachelates and the tetraligand of formula (II-a) for the manufacture of contrast agents for magnetic resonance imaging.

EFFECT: achievement of the absence of free paramagnetic metal ion in the composition, low viscosity of the composition, isotonicity of the composition to blood plasma and higher stability of the composition.

15 cl, 5 tbl, 5 ex