Back to results
US 5,508,388 AGranted
Process for manufacturing DTPA-bis amide magnetic resonance imaging
AssigneeMallinckrodt Medical, Inc.
InventorsLynn deLearie, Wayne H. Lin, Dennis A. Moore, David H. White
Life of this patent
Estimating the term…
Abstract
Processes for manufacturing diethylenetriaminepentaacetic acid ("DTPA") bis(amide) magnetic resonance imaging ("MRI") agents are disclosed. Specifically, processes for manufacturing [N,N"-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N',N"-tri acetato]gadolinium(III) are disclosed.
Claims23
A process for the production of a DTPA-bis(amide) paramagnetic metal complex comprising the steps of:
- (a) reacting DTPA with acetic anhydride in pyridine and acetonitrile to produce DTPA-bis(anhydride);
- (b) isolating and washing the DTPA-bis(anhydride) with a solvent comprising acetonitrile;
- (c) suspending the DTPA-bis(anhydride) in a solvent mixture comprising 2-propanol and acetonitrile;
- (d) reacting the suspended DTPA-bis(anhydride) with a primary or secondary amine, selected from the group of C.sub.1-6 alkylamine, C.sub.1-6 monohydroxyalkylamine, C.sub.1-6 polyhydroxyalkylamine, C.sub.1-6 alkoxyalkylamine, and C.sub.1-6 polyalkoxyalkylamine to produce a DTPA-bis(amide) complexing agent;
- (e) adding a cosolvent to solubilize the DTPA-bis(amide) complexing agent;
- (f) filtering the DTPA-bis(amide) to remove solid impurities and affecting crystallization of the DTPA-bis(amide) by addition of a crystallization solvent;
- (g) reacting the DTPA-bis(amide) with a paramagnetic metal ion, selected from a group of elements having atomic numbers of 21-25, 27-29, 42-44, and 58-70, to form a paramagnetic metal complex with the DTPA-bis(amide);
- (h) removing insoluble solids by filtration;
- and
- (i) crystallizing the DTPA-bis(amide) paramagnetic metal complex from the reaction mixture for final purification.
7 more elements
A process for the production of [N,N"-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N',N"-tri acetato]-gadolinium(III) comprising the steps of:
- (a) reacting DTPA with acetic anhydride in pyridine and acetonitrile to produce DTPA-bis(anhydride);
- (b) isolating and washing the DTPA-bis(anhydride) with a solvent comprising acetonitrile;
- (c) suspending the DTPA-bis(anhydride) in a solvent mixture comprising 2-propanol and acetonitrile;
- (d) reacting the suspended DTPA-bis(anhydride) with 2-methoxyethylamine to produce N,N"-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N',N"-tria cetic acid;
- (e) adding a cosolvent to solubilize the N,N"-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N',N"-tria cetic acid;
- (f) filtering the N,N"-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N',N"-tria cetic acid to remove solid impurities and affecting crystallizatoin of the N,N"-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N",N"-tria cetic acid by addition of a crystallization solvent;
- (g) reacting N,N"-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N',N"-tria cetic acid with gadolinium oxide to form [N,N"-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N',N"-tri acetato]-gadolinium(III);
- (h) removing insoluble solids by filtration;
- and
- (i) crystallizing [N,N"-Bis[N-(2-methoxyethyl)carbamoylmethyl]diethylenetriamine-N,N',N"-tri acetato]-gadolinium(III) from the reaction mixture for final purification.
7 more elements
Dependencies are inferred from the claim text.