Process for preparing crosslinked hyaluronic acid gel

• US 20060105022A1
• Filed: 11/14/2005
• Published: 05/18/2006
• Est. Priority Date: 11/15/2004
• Status: Abandoned Application

• Current Assignee: Shiseido Company Limited
• Original Assignee: Shiseido Company Limited
• Inventors: Ueno, Norio, Oka, Takashi, Mori, Yuichiro, Yokokawa, Yoshihiro
• Application Number:
  US11/272,914
• Publication Number:
  US 20060105022A1
• Time in Patent Office: Days
• US Class Current: 424/439
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates

Abstract

[PROBLEMS] A novel process which can simply prepare a crosslinked hyaluronic acid gel having a small crosslinking agent content and exhibiting excellent viscoelasticity is provided. [MEANS TO SOLVE] A method of producing cross-linking hyaluronic acid gel, comprising stirring and mixing a mixture containing 20 W/V % or more of hyaluronic acid, a crosslinking agent and water under acidic or alkaline condition.

Claims

1. A process for preparing a crosslinked hyaluronic acid gel, comprising stirring and mixing a mixture comprising 10 W/V % or more of hyaluronic acid, a crosslinking agent and water under acidic or alkaline conditions.

2. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the storage modulus G′

(frequency 1 Hz) of the mixture before said mixture is subjected to a crosslinking reaction of 15,000 Pa or higher.

3. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the mixture is stirred and mixed without physical cutting of a hyaluronic acid polymer chain in the mixture.

4. The process for preparing a crosslinked hyaluronic acid gel according to claim 3, wherein the mixture is stirred and mixed with a rotation/revolution mixer.

5. The process for preparing a crosslinked hyaluronic acid gel according to claim 3, wherein the mixture is stirred and mixed with a dough kneading machine or a rice-cake making machine.

6. The process for preparing a crosslinked hyaluronic acid gel according to claim 3, wherein the mixture is stirred and mixed by kneading with human hands.

7. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the crosslinking agent concentration in the mixture is 0.02 to 1 W/V %.

8. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the crosslinking agent concentration in the mixture is 0.02 to 2 W/W % relative to the quantity of hyaluronic acid disaccharide repeating units.

9. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the crosslinking agent is selected from the group consisting of divinylsulfone, 1,4-butanediol diglycidyl ether, and ethylene glycol diglycidyl ether.

10. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the storage modulus G′

(frequency 1 Hz) of the mixture before said mixture is subjected to a crosslinking reaction is 60,000 Pa or higher.

11. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, comprising stirring and mixing a mixture containing 11 W/V % to 41 W/V % of hyaluronic acid.

12. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, comprising stirring and mixing a mixture containing 11 W/V % to 18.2 W/V % of hyaluronic acid.

13. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, comprising stirring and mixing a mixture containing 18.2 W/V % to 33 W/V % of hyaluronic acid.

14. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, comprising stirring and mixing a mixture containing 33 W/V % to 41 W/V % of hyaluronic acid.

15. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the molecular weight of the hyaluronic acid is at least about 100,000.

16. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the molecular weight of the hyaluronic acid is at least about 500,000.

17. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the molecular weight of the hyaluronic acid is from about 500,000 to about 3,000,000.

18. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the crosslinking agent concentration in the mixture is 0.05 to 0.5 W/V %.

19. The process for preparing a crosslinked hyaluronic acid gel according to claim 1, wherein the crosslinking agent is selected from the group consisting of 1,3-butadiene diepoxide, 1,2,7,8-diepoxyoctane, 1,5-hexadiene diepoxide, and bisphenol A diglycidyl ether.

20. The process for preparing a crosslinked hyaluronic acid gel according to claim 5, wherein the mixture is stirred and mixed with a dough kneading machine or a rice-cake making machine at a rate of about 1000 to about 2000 RPM.