Water-soluble hyaluronic acid gel and method for producing same

• US 10,639,266 B2
• Filed: 06/27/2014
• Issued: 05/05/2020
• Est. Priority Date: 07/03/2013
• Status: Active Grant

• Current Assignee: Ritapharma, Co., Ltd.
• Original Assignee: Ritapharma, Co., Ltd.
• Inventors: Yoneto, Kunio
• Primary Examiner(s): Pallay, Michael B.
• Application Number:
  US14/892,282
• Publication Number:
  US 20160081906A1
• Time in Patent Office: 2,139 Days
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 8/24 Phosphorous; Compounds thereof
• CPC Class Codes: A61K 8/34 Alcohols
• CPC Class Codes: A61K 8/345 containing more than one hydroxy group
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/007 Preparations for dry skin
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
• CPC Class Codes: C08J 2305/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08K 3/24 Acids; Salts thereof C08K3/16 takes precedence
• CPC Class Codes: C08K 5/09 Carboxylic acids; Metal salts thereof; Anhydrides thereof
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

To provide a water-soluble hyaluronic acid gel which does not contain a large amount of an organic solvent, wherein hyaluronic acid is not chemically modified.

A water-soluble hyaluronic acid gel which contains hyaluronic acid, a polyhydric alcohol, an acid, and 0-10% by mass of a water-soluble organic solvent.

Claims

1. A water-soluble hyaluronic acid gel comprising hyaluronic acid acting as a gelling agent, a polyhydric alcohol, an acid and 0 to 10% by mass of a water-soluble organic solvent,

wherein the polyhydric alcohol comprises glycerin and a polyhydric alcohol other than glycerin at a ratio of 30:

10 to 4;

36 by mass,

wherein a content of hyaluronic acid is 0.2% by mass or more, and

wherein the water-soluble hyaluronic acid gel has high mechanical strength and a shape retention property, the high mechanical strength refers to strength to such an extent that a sheet made from the water-soluble hyaluronic acid gel which has a thickness of about 100 μ

m cannot be broken even when the sheet is held between fingers and is then pulled up.

2. The water-soluble hyaluronic acid gel according to claim 1, wherein the water-soluble hyaluronic acid gel is produced from an aqueous hyaluronic acid solution having a pH value falling within the range from 1.9 to 5.2, in which the aqueous hyaluronic acid solution is prepared by dissolving the components to be contained in the water-soluble hyaluronic acid gel, except the polyhydric alcohol and water, in water in such a manner that 200 parts by mass of water is contained relative to 1 part by mass of hyaluronic acid contained in the water-soluble hyaluronic acid gel.

3. The water-soluble hyaluronic acid gel according to claim 1, wherein the content of hyaluronic acid is 0.2 to 20% by mass.

4. The water-soluble hyaluronic acid gel according to claim 1, wherein the polyhydric alcohol is contained in an amount of 1 to 2000 parts by mass inclusive relative to 1 part by mass of hyaluronic acid.

5. The water-soluble hyaluronic acid gel according to claim 1, wherein water is contained in an amount of 700 parts by mass or less relative to 1 part by mass of hyaluronic acid.

6. The water-soluble hyaluronic acid gel according to claim 1, wherein the polyhydric alcohol comprises glycerin and a polyhydric alcohol other than glycerin at a ratio of 25:

15 to 4;

36 by mass.

7. The water-soluble hyaluronic acid gel according to claim 6, wherein the water-soluble hyaluronic acid gel is produced from an aqueous hyaluronic acid solution having a pH value falling within the range from 4.2 to 5.2, in which the aqueous hyaluronic acid solution is prepared by dissolving the components to be contained in the water-soluble hyaluronic acid gel, except the polyhydric alcohol and water, in water in such a manner that 200 parts by mass of water is contained relative to 1 part by mass of hyaluronic acid contained in the water-soluble hyaluronic acid gel.

8. The water-soluble hyaluronic acid gel according to claim 1, having a sheet form.

9. A water-soluble hyaluronic acid gel sheet comprising:

a support material; and

a water-soluble hyaluronic acid gel as recited in claim 1 which is formed on the support material.

10. A cosmetic comprising a water-soluble hyaluronic acid gel as recited in claim 1.

11. A pharmaceutical composition for external applications, comprising a water-soluble hyaluronic acid gel as recited in claim 1.

12. A composition for medical tools, comprising a water-soluble hyaluronic acid gel as recited in claim 1.

13. A method for producing a water-soluble hyaluronic acid gel, comprising a step of mixing hyaluronic acid, a polyhydric alcohol, an acid, 0 to 10% by mass of a water-soluble organic solvent and water together to prepare a gel-forming aqueous solution,

wherein the water-soluble hyaluronic acid gel comprises the hyaluronic acid acting as a gelling agent, the polyhydric alcohol, the acid and 0 to 10% by mass of the water-soluble organic solvent,

wherein the polyhydric alcohol comprises glycerin and a polyhydric alcohol other than glycerin at a ratio of 30:

10 to 4;

36 by mass,

wherein a content of hyaluronic acid is 0.2% by mass or more, and

wherein the water-soluble hyaluronic acid gel has high mechanical strength and a shape retention property, the high mechanical strength refers to strength to such an extent that a sheet made from the water-soluble hyaluronic acid gel which has a thickness of about 100 μ

m cannot be broken even when the sheet is held between fingers and is then pulled up.

14. The method for producing a water-soluble hyaluronic acid gel according to claim 13, further comprising a step of evaporating water contained in the gel-forming aqueous solution.

15. The method for producing a water-soluble hyaluronic acid gel according to claim 14, wherein the evaporation of water is carried out in such a state that the gel-forming aqueous solution is placed in a container.

16. The method for producing a water-soluble hyaluronic acid gel according to claim 14, further comprising a step of adding water after water contained in the gel-forming aqueous solution is evaporated.

17. A method for producing a water-soluble hyaluronic acid gel, comprising:

a step of mixing hyaluronic acid, a polyhydric alcohol, 0 to 10% by mass of a water-soluble organic solvent and water together to prepare an aqueous hyaluronic acid solution; and

a step of adding an acid to the aqueous hyaluronic acid solution,

wherein the water-soluble hyaluronic acid gel comprises the hyaluronic acid acting as a gelling agent, the polyhydric alcohol, the acid and 0 to 10% by mass of the water-soluble organic solvent,

wherein the polyhydric alcohol comprises glycerin and a polyhydric alcohol other than glycerin at a ratio of 30;

10 to 4;

36 by mass,

wherein a content of hyaluronic acid is 0.2% by mass or more, and

wherein the water-soluble hyaluronic acid gel has high mechanical strength and a shape retention property, the high mechanical strength refers to strength to such an extent that a sheet made from the water-soluble hyaluronic acid gel which has a thickness of about 100 μ

m cannot be broken even when the sheet is held between fingers and is then pulled up.

18. A method for producing a water-soluble hyaluronic acid gel, comprising:

a step of mixing hyaluronic acid, a polyhydric alcohol, 0 to 10% by mass of a water-soluble organic solvent and water together to prepare an aqueous hyaluronic acid solution;

a step of drying the aqueous hyaluronic acid solution; and

a step of adding an acid to the dried aqueous hyaluronic acid solution,

wherein the water-soluble hyaluronic acid gel comprises the hyaluronic acid acting as a gelling agent, the polyhydric alcohol, the acid and 0 to 10% by mass of the water-soluble organic solvent,

wherein the polyhydric alcohol comprises glycerin and a polyhydric alcohol other than glycerin at a ratio of 30;

10 to 4;

36 by mass,

wherein a content of hyaluronic acid is 0.2% by mass or more, and

wherein the water-soluble hyaluronic acid gel has high mechanical strength and a shape retention property, the high mechanical strength refers to such an extent that a sheet made from the water-soluble hyaluronic acid gel which has a thickness of about 100 μ

m cannot be broken even when the sheet is held between fingers and is then pulled up.