COMPOSITIONS OF METAL COMPLEXES Russian patent published in 2019 - IPC A61K49/10 A61K33/244 

FIELD: medicine; pharmaceuticals.

SUBSTANCE: group of inventions relates to the field of medicine and pharmaceuticals. First invention represents a method for preparing a liquid pharmaceutical formulation comprising: (i) formation of a chelator complex with excess lanthanide metal in a suitable solvent to obtain a first solution of a metal complex containing excess lanthanide; (ii) removing excess lanthanide from the first solution by contacting one or more times with the acceptor resin, whereby excess lanthanide forms a complex with said acceptor resin; (iii) separating the acceptor resin from the first solution to obtain a second solution which contains a metal complex which does not contain excess lanthanide; (iv) adding a chelator in an uncombined form in range of 0.002 to 0.4 mol. % to a second solution to obtain a liquid pharmaceutical composition, in which the lanthanide metal is gadolinium; macrocyclic chelator contains DOTA, NOTA, DO3A, BT-DO3A, HP-DO3A and PCTA; chelator in uncomplexed form does not contain coordinated metal ions, and acceptor resin is bound to solid phase acceptor chelator, which is present in form of meglumine salt of acceptor chelator. Second invention represents a method for preparing a contrast agent for MRI; third invention relates to a chelator which is bound to a solid phase, which is iminodiacetic acid in form of a meglumine salt; fourth invention relates to use of said solid phase bound chelator.

EFFECT: group of inventions widens the range of methods for producing macrocyclic complexes of gadolinium with excess chelator; according to method there is no need for measurement and control stages, and minimum content of sodium ions is also provided.

16 cl, 2 dwg, 1 tbl, 6 ex