Patent ID: 9352056
Filing Date: 2016-05-31
CPC Classification: A61K

Claim Text:
1. A method for preparing a pharmaceutical formulation of a macrocyclic chelate of a lanthanide, wherein the macrocyclic chelate is 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA), the lanthanide is gadolinium (Gd), and the macrocyclic chelate of a lanthanide is a DOTA-Gd complex, said method comprising the following successive steps of: (1) mixing in a solution a macrocyclic chelate and a lanthanide so as to obtain a complexation solution of the lanthanide by the macrocyclic chelate, the complexation solution comprising, in addition to the macrocyclic chelate-lanthanide complex, an excess amount X1 of free macrocyclic chelate, wherein a step (1) is carried out in a single step or in several successive steps by measuring and adjusting, so as to have an amount X1 of free macrocyclic chelate, and the step (1) comprises the following successive substeps of: (2) optionally measuring X1 and/or adjusting X1 so as to have X1 between 0.002 and 0.4% mol/mol; (3) precipitating or crystallizing the complexation solution obtained in step (1) at a pH in the range 1 to 9 from an organic solvent and at a temperature in the range 0° C. to 80° C., wherein said solvent is employed at a volume ratio to the complexation solution in the range 10:1 to 20:1, so as to obtain a powder of the macrocyclic chelate-lanthanide complex, said powder containing an excess amount X2 of free macrocyclic chelate, wherein X2 represents the amount of free macrocyclic chelate obtained after precipitation or crystallization and X2 is less than X1, (4) adjusting X2 by adding free macrocyclic chelate so as to obtain: wherein said powder obtained after step (4) comprises a mol/mol excess of free macrocyclic chelate of between 0.002 and 0.4%; and (5) returning said powder to solution so as to form a pharmaceutical composition in liquid form, said pharmaceutical composition in liquid form being ready for administration to a patient.