Purification method of azacyclohexapeptide or its salt

Patent metadata

Field	Value
Publication number	US-9233318-B2
Application number	US-201113640836-A
Country	US
Kind code	B2
Filing date	Apr 15, 2011
Priority date	Apr 15, 2010
Publication date	Jan 12, 2016
Grant date	Jan 12, 2016

Abstract

A purification method of the compound represented by formula 1 is provided, which includes the following steps: (1) loading crude compound 1 on macroporous adsorbent resin, (2) washing the macroporous adsorbent resin with an aqueous solution, an organic solvent or a mixture solution of organic solvent and water, (3) eluting with an aqueous solution, an organic solvent or a mixture solution of organic solvent and water. The purified compound represented by formula 1 is obtained.

First claim

What is claimed is:

1. A purification process for the compound of Formula 1, wherein said process comprising:
(1) loading a crude compound 1 onto a macroporous adsorption resin;
(2) washing the macroporous adsorption resin with an aqueous solution, an organic solvent or a mixed solution of an organic solvent and water;
(3) eluting with an aqueous solution, an organic solvent or a mixed solution of an organic solvent and water to give a purified compound of Formula 1;

wherein the macroporous adsorption resin is selected from a non-polar aromatic adsorption resin polymerized from styrene and divinylbenzene, or a moderately polar methacrylic adsorption resin comprising methacrylate unit in its structure;
the organic solvent is selected from methanol, ethanol, or C 1 -C 4 ketone,
the concentration gradient of the organic solvent is 10%-60% (v/v), and
the pH of the aqueous solution, the organic solvent or the Mixed solution of an organic solvent and water is ≧7.

2. The purification process according to claim 1 , wherein the macroporous adsorption resin is selected from one or more of the following resins: XAD-1, XAD-2, XAD-3, XAD-4, XAD-5, XAD-16, XAD-16HP; or from one or more of the following resins: HP-10, HP-20, HP-20ss, HP-21, HP-30, HP-40, HR-50, SP-825, SP-850, SP-70, SP-700, SP-207; or from one or more of the following resins: XAD-6, XAD-7, XAD-7HP, XAD-8; or HP-2MG.

3. The purification process according to claim 1 , wherein step (3) is followed by:
(4) crystallizing the purified compound of Formula 1 to give a compound of Formula 1 having a purity of greater than 99%.

4. The purification process according to claim 1 , wherein the pH is 4.5-6.0.

5. The purification process according to claim 1 , wherein the pH is 5.0-5.5.

6. The purification process according to claim wherein the concentration gradient of methanol or ethanol is 25%-50% (v/v).

7. The purification process according to claim 2 , wherein the concentration gradient of methanol or ethanol is 25%, 30%, 50% (v/v).

8. The purification process according to claim 1 , wherein the concentration gradient of C 1 -C 4 ketone is 10%-50% (v/v).

9. The purification process according to claim 1 , wherein the concentration gradient C 1 -C 4 ketone is 10%, 20%, 25% (V/V); 20%, 30%, 40% (V/V); 30%, 40%, 50% (V/V); 20%, 40%, 50% (V/V); 10%, 20%, 25% (V/V); 20%, 30%, 40% (V/V); 30%, 40%, 50% (V/V); or 20%, 40%, 50% (V/V).

10. The purification process according to claim 1 , wherein the C 1 -C 4 ketone is acetone.

11. The purification process according to claim 1 , wherein the aqueous solution the organic solvent and the mixed solution of an organic solvent and water contains 0.016% (V/V) acetic acid.

Assignees

• Zhuo Zhonghao
• Tang Zhijun
• Xu Tianhui
• Li Ming
• Ji Xiaoming
• Gao Xiaoliang
• Shanghai Techwell Biopharm Co

Inventors

• Zhuo Zhonghao
• Tang Zhijun
• Xu Tianhui
• Li Ming
• Ji Xiaoming
• Gao Xiaoliang

Classifications

• C07K7/54

  with at least one abnormal peptide link in the ring · CPC title

• C07K1/14

  Extraction; Separation; Purification · CPC title

• B01D15/424

  Elution mode · CPC title

• B01D15/426

  Specific type of solvent · CPC title

• C07K1/16

  by chromatography · CPC title