Claims for Patent: 10,973,934

Summary for Patent: 10,973,934

Title:	Gadolinium bearing PCTA-based contrast agents
Abstract:	The present invention relates to the RRR/SSS pair of enantiomers of the of Gd(PCTA-tris-glutaric acid), the single enantiomers of the pair, the pharmaceutically acceptable salts thereof, their amide derivatives, and compositions comprising at least 50% of these compounds.
Inventor(s):	Napolitano Roberta, Lattuada Luciano, Baranyai Zsolt, Guidolin Nicole, Marazzi Giuseppe
Assignee:	BRACCO IMAGING S.P.A.
Application Number:	US16766619
Patent Claims:	2. The isomeric mixture of wherein the pharmaceutically acceptable salt is with (i) a cation of an inorganic base selected from an alkali-earth metal claim 1 , alkaline-earth metal claim 1 , potassium claim 1 , sodium claim 1 , calcium and magnesium claim 1 , or of (ii) an organic base selected from ethanolamine claim 1 , diethanolamine claim 1 , morpholine claim 1 , glucamine claim 1 , N-methylglucamine claim 1 , and N claim 1 ,N-dimethylglucamine or of (iii) an amino acid selected from lysine claim 1 , arginine and ornithine or with (iv) an anions of inorganic acids selected from halo acids claim 1 , chlorides claim 1 , bromides and iodides claim 1 , or of (v) other suitable ions selected from acetate claim 1 , succinate claim 1 , citrate claim 1 , fumarate claim 1 , maleate and oxalate.4. The isomeric mixture according to comprising at least 50% of an amide derivative selected from the group consisting of: [(αS claim 3 ,α′S claim 3 ,α″S)-α claim 3 ,α′ claim 3 ,α″-tris[3-[(2(S) claim 3 ,3-dihydroxypropyl)amino]-3-oxopropyl]-3 claim 3 ,6 claim 3 ,9 claim 3 ,15-tetraazabicyclo[9.3.1]pentadeca-1(15) claim 3 , 11 claim 3 ,13-triene-3 claim 3 ,6 claim 3 ,9-triacetato(3-)-κN3 claim 3 ,κN6 claim 3 ,κN9 claim 3 ,κN15 claim 3 ,κO3 claim 3 ,κO6 claim 3 ,κO9]-gadolinium (isomer SSS-SSS); [(αS claim 3 ,α′S claim 3 ,α″S)-α claim 3 ,α′ claim 3 ,α″-tris[3-[(2(R) claim 3 ,3-dihydroxypropyl)amino]-3-oxopropyl]-3 claim 3 ,6 claim 3 ,9 claim 3 ,15-tetraazabicyclo[9.3.1]pentadeca-1(15) claim 3 , 11 claim 3 ,13-triene-3 claim 3 ,6 claim 3 ,9-triacetato(3-)-κN3 claim 3 ,κN6 claim 3 ,κN9 claim 3 ,κN15 claim 3 ,κO3 claim 3 ,κO6 claim 3 ,κO9]-gadolinium (isomer SSS-RRR); [(αR claim 3 ,α′R claim 3 ,α″R)-α claim 3 ,α′ claim 3 ,α″-tris[3-[(2(R) claim 3 ,3-dihydroxypropyl)amino]-3-oxopropyl]-3 claim 3 ,6 claim 3 ,9 claim 3 ,15-tetraazabicyclo[9.3.1]pentadeca-1(15) claim 3 ,11 claim 3 ,13-triene-3 claim 3 ,6 claim 3 ,9-triacetato(3-)-κN3 claim 3 ,κN6 claim 3 ,κN9 claim 3 ,κN15 claim 3 ,κO3 claim 3 ,κO6 claim 3 ,κO9]-gadolinium (isomer RRR-RRR); [(αR claim 3 ,α′R claim 3 ,α″R)-α claim 3 ,α′ claim 3 ,α″-tris[3-[(2(S) claim 3 ,3-dihydroxypropyl)amino]-3-oxopropyl]-3 claim 3 ,6 claim 3 ,9 claim 3 ,15-tetraazabicyclo[9.3.1]pentadeca-1(15) claim 3 , 11 claim 3 ,13-triene-3 claim 3 ,6 claim 3 ,9-triacetato(3-)-κN3 claim 3 ,κN6 claim 3 ,κN9 claim 3 ,κN15 claim 3 ,κO3 claim 3 ,κO6 claim 3 ,κO9]-gadolinium (isomer RRR-SSS); and mixtures thereof.5. The isomeric mixture according to in which in the formula (II B) F′ comprises at least 60% of the mixture of RRR and SSS enantiomer residues.6. A pharmaceutical composition comprising the isomeric mixture according to in admixture with one or more pharmaceutically acceptable carriers claim 1 , diluents or excipients.7. A pharmaceutical composition comprising an isomeric mixture of an amide derivative of formula (II B) according to in admixture with one or more pharmaceutically acceptable carriers claim 3 , diluents or excipients.8. The pharmaceutical composition according to in which in the formula (II B) Ris H and Ris —CHCH(OH)CHOH.9. The isomeric mixture according to in which in the formula (II B) F′ comprises at least 70% of the RRR and SSS enantiomers residues.10. The isomeric mixture according to in which in the formula (II B) F′ comprises at least 80% of the RRR and SSS enantiomers residues.11. The isomeric mixture according to in which in the formula (II B) F′ comprises at least 90% of the RRR and SSS enantiomers residues.12. The isomeric mixture according to claim 3 , wherein Ris a C-Calkyl substituted by one or two hydroxyl groups.13. The isomeric mixture according to wherein claim 3 , in the formula (II B) claim 3 , Ris H and Ris C-Calkyl substituted by one or two hydroxyl groups.14. The isomeric mixture according to wherein claim 13 , in the formula (II B) claim 13 , Ris H and Ris —CHCH(OH)CHOH.15. The pharmaceutical composition according to in which in the formula (II B) F′ comprises at least 70% of the RRR and SSS enantiomers residues.16. The isomeric mixture of wherein the pharmaceutically acceptable salt is with a cation of an inorganic base selected from potassium claim 2 , sodium claim 2 , calcium and magnesium.