Dual functioning excipient for metal chelate contrast agents
View Patent ↗A novel dual functioning excipient for metal chelate contrast agents is disclosed. The present excipient, X m [X′(L′)] n , which is the calcium or zinc salt of the calcium or zinc complex of an organic ligand, enhances safety in that it is able to scavenge both free metal ions and free organic ligand.
1. A composition for use in magnetic resonance, x-ray, ultrasound and radio-diagnostic imaging comprising:
a contrast agent of the formula
M(L)
where M is a metal ion and L is an organic ligand of the formula
wherein
Y is
R 1 is hydroxypropyl and R 2 is H; and
a complex salt excipient of the formula
X m [X′(L′)] n
wherein X and X′ are calcium; L′ is
wherein
Y is
R 1 is hydroxypropyl and R 2 is H;
m is 1 and n is 2.
2. The composition of claim 1 wherein L and L′ are each 1,4,7-tris(carboxymethyl)-10-(2′-hydroxypropyl)-1,4,7,10-tetraazacyclododecane.
3. The composition of claim 1 wherein the mole ratio of said complex salt excipient to said contrast agent is between about 0.05 and 10 percent.
4. The composition of claim 1 wherein said metal ion is selected from paramagnetic metal atoms, lanthanide series elements, yttrium, and the transition series elements.
5. The composition of claim 4 wherein said paramagnetic metals are selected from gadolinium(III), dysprosium(III), manganese(II), manganese(III), chromium(III), iron(II) and iron(III).
6. The composition of claim 1 wherein said metal ion M complexed with an organic ligand is gadolinium(III) 1,4,7-tris(carboxymethyl)-10-(2′-hydroxypropyl)-1,4,7,10-tetraazacyclododecane and said excipient is calcium bis[1,4,7-tris(carboxy-methyl)-10-(2′-hydroxypropyl)-1,4,7,10-tetraazacyclododecanatocalcium(II)].