Method for producing alpha-form crystal of reduced glutathione, and method for storing said crystal

Patent metadata

Field	Value
Publication number	US-10407463-B2
Application number	US-201615579592-A
Country	US
Kind code	B2
Filing date	Jun 3, 2016
Priority date	Jun 5, 2015
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

The invention provides a method of efficiently and stably producing α-form crystal of reduced glutathione, and a preservation method thereof. According to the invention, development of β-form crystal and/or transition to β-form crystal of reduced glutathione are suppressed by the coexistence of at least one kind of compound selected from the group of aliphatic amino acid, sulfur-containing amino acid, aromatic amino acid, an analogous compound and dipeptide, as a habit modifier, during production and preservation of an aqueous solution or α-form crystal of reduced glutathione.

First claim

The invention claimed is:

1. A production method of an α-form crystal of reduced glutathione, comprising a step of adding a habit modifier to an aqueous solution containing the reduced glutathione, and a step of crystallizing reduced glutathione as an α-form crystal, wherein the habit modifier is at least one compound selected from the group consisting of an aliphatic amino acid, a sulfur-containing amino acid, an aromatic amino acid, a dipeptide, oxidized glutathione, N-L-cysteinylqlycine, and γ glutamylcysteine.

2. The method according to claim 1 , wherein the habit modifier is added in an amount of 0.01-10 wt % relative to the reduced glutathione.

3. The method according to claim 1 , wherein the habit modifier is an aliphatic amino acid.

4. The method according to claim 3 , wherein the aliphatic amino acid is selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, and proline.

5. The method according to claim 3 , wherein the aliphatic amino acid is L-alanine or D-proline.

6. The method according to claim 1 , wherein the habit modifier is a sulfur-containing amino acid.

7. The method according to claim 6 , wherein the sulfur-containing amino acid is selected from the group consisting of cysteine, homocysteine, and methionine.

8. The method according to claim 6 , wherein the sulfur-containing amino acid is L-cysteine.

9. The method according to claim 1 , wherein the habit modifier is an aromatic amino acid.

10. The method according to claim 9 , wherein the aromatic amino acid is selected from the group consisting of phenylalanine, tryptophan, and tyrosine.

11. The method according to claim 9 , wherein the aromatic amino acid is L-phenylalanine or L-tryptophan.

12. The method according to claim 1 , wherein the habit modifier is a dipeptide.

13. The method according to claim 12 , wherein the dipeptide is L-alanine-L-glutamine.

14. The method according to claim 12 , wherein the dipeptide is L-alanyl-L-cysteine.

15. The method according to claim 1 , wherein the habit modifier is oxidized glutathione.

16. The method according to claim 1 , wherein the habit modifier is N-L-cysteinylglycine.

17. The method according to claim 1 , wherein the habit modifier is γ glutamylcysteine.

Assignees

• Kyowa Hakko Bio Co Ltd

Inventors

• Iguchi Maya
• Fukumoto Kazunari
• Nagano Hiroshi

Classifications

• C07K1/02

  in solution {(C07K1/003, C07K1/006 take precedence)} · CPC title

• C07K5/08

  Tripeptides · CPC title

• C07K5/0215 Primary

  containing natural amino acids, forming a peptide bond via their side chain functional group, e.g. epsilon-Lys, gamma-Glu · CPC title

• C07K5/06

  Dipeptides · CPC title

• C07K1/306 Primary

  by crystallization · CPC title