# US 2013/0277221 A1 · Desalination of a composition comprising a contrast agent > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0277221 A1 - Document ID: US20130277221A1 - Status: Published application - Kind: A1 - Application number: 13/995,588 - Filed: 2011-12-20 - Published: 2013-10-24 - Earliest claimed: 2010-12-21 - Assignees: Ge Healthcare Limited - Inventors: Aslaug Birkeland - Web page: https://patentgrep.com/patent/US20130277221A1 ## CPC - A61K 49/0002: {General or multifunctional contrast agents, e.g. chelated agents} - A61K 49/0438: {Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol} - A61K 49/0442: {Polymeric X-ray contrast-enhancing agent comprising a halogenated group} - B01D 61/422: {Electrodialysis} - B01D 61/44: Ion-selective electrodialysis - B01D 61/58: Multistep processes - C02F 1/4695: {electrodeionisation} - C07C 231/24: Separation; Purification - Y02A 20/124: Water desalination - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28) - C02F: TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE (separation in general B01D; special arrangements on waterborne vessels of installations for treating water, waste water or sewage, e.g. for producing fresh water, B63J; adding materials to water to prevent corrosion C23F; treating radioactively-contaminated liquids G21F9/04; regeneration of reactants for recirculation into processes, see the relevant places for the processes) - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The invention relates to industrial preparation of contrast agents, and further to an improved process for the purification of contrast agents. In particular, it relates to a process for reducing the salt content of compositions comprising an MR contrast agent or an X-ray contrast agent, such as a non-ionic iodinated monomeric compound or a non-ionic iodinated dimeric compound. ## Claims ### Claim 1 A process for the preparation of a composition comprising a contrast agent in a carrier, the process comprising the step of desalinating the composition by electrodeionization (EDI) using a wafer based EDI device. ### Claim 2 (depends on 1) A process as claimed in claim 1 wherein the contrast agent is an MR contrast agent or an X-ray contrast agent selected from a non-ionic iodinated monomeric compound and a non-ionic iodinated dimeric compound. ### Claim 3 (depends on 1, 2, 3) A process as claimed in any of claims 1 to 3 wherein the contrast agent is selected from iohexol, iodixanol and ioforminol. ### Claim 4 (depends on 1, 2, 3) A process as claimed in any of claims 1 to 3 wherein the electrodeionization step takes place before or after the contrast agent is crystallized. ### Claim 5 (depends on 1, 2, 3, 4) A process as claimed in any of claims 1 to 4 wherein the contrast agent is iohexol, the process comprising the step of desalinating a crude composition comprising iohexol by electrodeionization using a wafer based EDI device, including the sequential steps of: (1) reducing the salt content in a crude composition which is the reaction mixture comprising Compound A, salts and iohexol, by EDI; (2) crystallizing iohexol from the composition of step (1). ### Claim 6 (depends on 1, 2, 3, 4) A process as claimed in any of claims 1 to 4 wherein the contrast agent is iodixanol, the process comprising the step of desalinating a crude composition comprising iodixanol by electrodeionization using a wafer based EDI device, including the sequential steps of: (1) reducing the salt content in a crude composition which is the reaction mixture comprising Compound A, salts and iodixanol, by EDI; (2) recovering Compound A in the composition of (1) after desalination, for reuse in a subsequent dimerisation reaction to prepare iodixanol; and (3) crystallizing iodixanol from the composition of step (1). ### Claim 7 (depends on 4, 5, 6) A process as claimed in any of claims 4 to 6, wherein the crystallized contrast agent, is subjected to the additional bulk treatment steps of: a) solving the crystallized contrast agent in water, b) purifying the composition from step (a), c) drying the composition from step (b). ### Claim 8 (depends on 7) A process as claimed in claim 7 wherein the purification step b) includes removal of salts by electrodeionization. ### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8) A process as claimed in any of the claims 1 to 8 wherein the salt content in the composition after the process has been conducted is less than about 1.0%, compared to the contrast agent content. ### Claim 10 (depends on 9) A process as claimed in claim 9 wherein the salt content of the composition comprising iodixanol is less than about 0.7 weight % compared to the iodixanol content. ### Claim 11 (depends on 9) A process as claimed in claim 9 wherein the salt content of the composition comprising iohexol is less than about 0.02 weight % compared to the iohexol content. ### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11) A process as claimed in any of claims 1 to 11 wherein the process is included in a continuous process for preparing an X-ray contrast agent. ### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) A process as claimed in any of claims 1 to 12 wherein the process is combined with additional purification and/or desalinating by a method selected from filtrations, ion exchange and electrodialysis (ED). ### Claim 14 (depends on 13) A process as claimed in claim 13 wherein the process includes additional desalinating by ED in a separate step before or after the EDI step. ### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14) A process as claimed in any of claims 1 to 14 wherein the composition comprising the contrast agent subjected to desalinating is a side stream or waste stream from a process of preparing the contrast agent, the composition comprising minor amounts of the contrast agent. ### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14) A process as claimed in any of claims 1 to 14 wherein the EDI device used comprises ion exchange resins, membranes and means for applying a DC voltage, wherein the ion exchange resins are moulded into a porous wafer.