# US 8,541,620 B2 · Method for selectively crystallizing a Z isomer of iopromide

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- Number: US 8,541,620 B2
- Document ID: US8541620B2
- Status: Granted
- Kind: B2
- Application number: 13/132,791
- Filed: 2009-10-21
- Published: 2011-10-06
- Granted: 2013-09-24
- Earliest claimed: 2008-12-05
- Assignees: Daewoong Pharmaceutical Co., Ltd.
- Applicants: Soo-Jin Choi; Byung-Goo Lee; Han-Kuk Lee; Young-Mook Lim; Wol-Young Kim; Joon-Hwan Lee
- Inventors: Soo-Jin Choi; Byung-Goo Lee; Han-Kuk Lee; Young-Mook Lim; Wol-Young Kim; Joon-Hwan Lee
- Web page: https://patentgrep.com/patent/US8541620B2

## CPC

- C07C 231/24: Separation; Purification
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention relates to a method for selectively crystallizing Z isomer of iopromide of formula (I) comprising a) dissolving a crude iopromide comprising a mixture of E and Z isomers or a concentrate thereof in an alcohol, and b) heating the resulting alcohol solution to obtain crystalline of Z isomer of iopromide; and a method for preparing a composition comprising the crystalline Z isomer of iopromide.

## Claims

### Claim 1

A method for selectively crystallizing Z isomer of iopromide represented by the following formula (I):
said method comprising:
a) dissolving crude iopromide or a concentrate thereof containing E and Z form isomers in an alcohol; and
b) heating the resulting alcohol solution of the crude iopromide or the concentrate at a temperature ranging from 80° C. to 180° C. for 6-48 hours to obtain a crystalline iopromide comprising Z form isomer in an amount of 85-100% based on the total amount of the crystalline Z isomer of iopromide.

### Claim 2 (depends on 1)

The method of claim 1, wherein the content of Z isomer of iopromide crystal obtained in step b) ranges from 95% to 100%.

### Claim 3 (depends on 1)

The method of claim 1, wherein the alcohol is a straight or branched C1-9 aliphatic alcohol.

### Claim 4 (depends on 1)

The method of claim 1, wherein the volume (ml) of the alcohol is 0.1 to 10 times the weight (g) of the crude iopromide crystal or the concentrate thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein the E isomer to Z isomer ratio of in the crude iopromide or the concentrate thereof ranges from 1:0.5 to 1:10.

### Claim 6 (depends on 1)

The method of claim 1, wherein the moisture content of the crude crystal or the concentrate thereof ranges from 0 wt % to 15 wt %.

### Claim 7

A method for preparing a composition comprising Z isomer of iopromide of the following formula (I) comprising
a) dissolving crude iopromide or a concentrate thereof containing E and Z form isomers in an alcohol;
b) heating the resulting alcohol solution of the crude iopromide or the concentrate at a temperature ranging from 80° C. to 180° C. for 6-48 hours to obtain a crystalline iopromide comprising Z form isomer in an amount of 85-100% based on the total amount of the crystalline iopromide; and
c) dissolving the crystalline iopromide in a solvent, together with a pharmaceutically acceptable excipient to give a composition comprising 32-40 wt % of Z1 isomer of iopromide and 38-46 wt % of Z2 isomer of iopromide,

### Claim 8 (depends on 7)

The method of claim 7, wherein the content of Z isomer of iopromide of the crystal ranges from 95% to 100%.

### Claim 9 (depends on 7)

The method of claim 7, wherein the alcohol is a straight or branched C1-10 aliphatic alcohol.

### Claim 10 (depends on 7)

The method of claim 7, wherein the volume (ml) of the alcohol is 0.1 to 10 times weight (g) of the crude iopromide crystal or the concentrate thereof.

### Claim 11 (depends on 7)

The method of claim 7, wherein the ratio of E isomer to Z isomer ratio of in the crude iopromide or the concentrates thereof ranges from 1:0.5 to 1:10.

### Claim 12 (depends on 7)

The method of claim 7, wherein the moisture content of the crude crystal or the concentrate thereof ranges from 0 wt % to 15 wt %.