Method for preparing a chitosan-based matrix comprising a fiber reinforcement member

• US 10,184,032 B2
• Filed: 01/22/2016
• Issued: 01/22/2019
• Est. Priority Date: 02/17/2015
• Status: Active Grant

• Current Assignee: Sofradim Production
• Original Assignee: Sofradim Production
• Inventors: Serrero, Aurelie, Desorme, Mylene
• Primary Examiner(s): Pak, Hannah J
• Application Number:
  US15/003,975
• Publication Number:
  US 20160237228A1
• Time in Patent Office: 1,096 Days
• CPC Class Codes: A61K 31/722 Chitin, chitosan
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
• CPC Class Codes: C08J 2305/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 5/046 with synthetic macromolecular fibrous material
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 67/02 Polyesters derived from dicarboxylic acids and dihydroxy compounds C08L67/06 takes precedence

Abstract

The present invention relates to a method for preparing a chitosan-based matrix comprising the following steps:

• • a) two separate chitosan porous layers obtained from lyophilization of layers of one or more solutions of chitosan are provided,
  • b) the chitosan porous layers of a) are neutralized and washed,
  • c) a face of each chitosan porous layer is acidified with an acid,
  • d) a fiber reinforcement member is provided and positioned between the two acidified faces of the two chitosan porous layers,
  • e) the two chitosan porous layers and the fiber reinforcement member are let to dry to obtain a matrix having the fiber reinforcement member embedded therein. The invention also relates to an implant comprising a matrix obtained according to such a method.

Claims

1. A method for preparing a chitosan-based matrix comprising a fiber reinforcement member embedded in the matrix comprising:

a) providing one or more solutions including chitosan,

b) obtaining two separate chitosan porous layers from lyophilisation of the one or more solutions of chitosan,

c) neutralizing the chitosan porous layers of b),

d) washing the chitosan porous layers of c),

e) applying an acid to a face of each of the chitosan porous layers of d),

f) positioning a fiber reinforcement member between the two acidified faces of the two chitosan porous layers of e),

g) drying the two chitosan porous layers and the fiber reinforcement member of f) to obtain a matrix having the fiber reinforcement member embedded therein.

2. The method according to claim 1, wherein providing one or more solutions including chitosan comprises a solution of chitosan in water, the chitosan including a concentration in the solution ranging from 0.1% to 10% by weight, relative to a total weight of the solution.

3. The method according to claim 1, wherein providing one or more solutions including chitosan comprises a solution of chitosan in water, the chitosan including a concentration in the solution ranging from 0.5% to 3% by weight, relative to a total weight of the solution.

4. The method according to claim 1, wherein providing one or more solutions including chitosan comprises a solution of chitosan in water, the chitosan including a concentration in the solution ranging from 0.8% to 1% by weight, relative to a total weight of the solution.

5. The method according to claim 1, further comprising adjusting a pH of the one or more solutions in a) to a value ranging from 3 to 5.

6. The method according to claim 1, further comprising adjusting a pH of the one or more solutions in a) to a value of 3.5.

7. The method according to claim 5, wherein adjusting a pH of the one or more solutions in a) comprises adding acetic acid to the one or more of solutions.

8. The method according to claim 1, wherein applying an acid according to e) comprises spraying a solution of the acid on the face.

9. The method according to claim 1, wherein the acid according to e) is selected from the group consisting of acetic acid, hydrochloric acid, citric acid, sulphuric acid, lactic acid, and mixtures thereof.

10. The method according to claim 1, wherein the acid according to e) comprises acetic acid.

11. The method according to claim 10, wherein applying the acid according to e) comprises spraying a solution of acetic acid at 0.1 M on the face of each of the chitosan porous layers.

12. The method according to claim 11, wherein the spraying is repeated twice.

13. The method of claim 1, further comprising impregnating the fiber reinforcement member with a solution of an acid before being positioned between the two acidified faces of the two chitosan porous layers of e).

14. The method according to claim 13, wherein the solution of the acid comprises an acid selected from the group consisting of acetic acid, hydrochloric acid, citric acid, sulphuric acid, lactic acid, and mixtures thereof.

15. The method according to claim 13, wherein the solution of the acid comprises acetic acid.

16. The method according to claim 15, wherein the solution of the acid comprises a solution of acetic acid at 0.1 M.

17. The method according to claim 1, wherein the chitosan porous layers and the fiber reinforcement member have substantially bidimensional structures, and an area of the fiber reinforcement member is smaller than an area of each chitosan porous layer.

18. The method according to claim 1, wherein the fiber reinforcement member is a porous mesh.

19. The method according to claim 1, further comprising applying a pressure on the chitosan porous layers in a direction of the fiber reinforcement member during and/or after the positioning a fiber reinforcement member between the two acidified faces of the two chitosan porous layers of e).

20. The method according to claim 1, wherein neutralizing the chitosan porous layers of b) comprises immersing the chitosan porous layers of a) in a basic solution.

21. The method according to claim 20, wherein the basic solution comprises NaOH or NH₄OH in water or an alcohol.

22. The method according to claim 1, wherein washing the chitosan porous layers of c) comprises dipping the chitosan porous layers of c) in one or more baths of sterile water until a washing water with a pH close to 7 is obtained.

23. The method according to claim 1, wherein applying an acid to a face of each of the chitosan porous layers of d) further comprises obtaining a superficial layer on the face of each of the chitosan porous layers so as to cause a resolubilization of the superficial layer of each face.

24. The method according to claim 23, wherein the superficial layer comprises a thickness up to 5% of a total thickness of each chitosan porous layer.