Chitin hydrogels, methods of their production and use

• US 6,124,273 A
• Filed: 10/13/1997
• Issued: 09/26/2000
• Est. Priority Date: 06/09/1995
• Status: Expired due to Term

• Current Assignee: American National Red Cross, Coalition For Hemophilia B Incorporated, Chitogenics, Inc. (Kytogenics Pharmaceuticals, Inc.)
• Original Assignee: American National Red Cross, Coalition For Hemophilia B Incorporated, Chitogenics, Inc. (Kytogenics Pharmaceuticals, Inc.)
• Inventors: Singh, Manish S., Drohan, William N., Elson, Clive, MacPhee, Martin J., Miekka, Shirley I., Taylor, John R. Jr.
• Primary Examiner(s): FONDA, KATHLEEN KAHLER
• Application Number:
  US08/960,555
• Time in Patent Office: 1,079 Days
• Field of Search: 514/2, 514/55, 536/20
• US Class Current: 514/55
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/37 Factors VIII
• CPC Class Codes: A61K 38/4846 Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
• 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 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 26/0023 Polysaccharides
• CPC Class Codes: A61L 26/0047 Specific proteins or polypeptides not covered by groups A61L26/0033 - A61L26/0042
• CPC Class Codes: A61L 26/0066 Medicaments; Biocides
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• 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: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

This invention is directed to the preparation and utilization of supplemented chitin hydrogels, such as chitosan hydrogels. Further provided are biomaterials comprising same. The particular supplement delivered by the chitin hydrogel is selected as a function of its intended use. In one embodiment, this invention provides a composition of matter, comprising a chitin hydrogel or chitin-derived hydrogel, wherein the hydrogel does not inhibit full-thickness skin wound healing.

Claims

1. A composition of matter that provides sustained release of proteins, said composition comprising a covalently cross-linked N,O-carboxymethyl chitosan hydrogel having a protein to be delivered incorporated therein in sufficient concentration to provide said sustained release.

2. The composition of claim 1, wherein said protein is selected from the group consisting of plasma proteins and osteogenic proteins.

3. The composition of claim 2, wherein said plasma proteins are selected from the group consisting of Factor IX, Factor VIII, and mixtures thereof.

4. The composition of claim 2, wherein said osteogenic protein comprises bone morphogenic protein.

5. The composition of claim 4, further comprising a bone growth promoting substance selected from the group consisting of bone marrow cells, bone chips, hydroxyapatite, and mixtures thereof.

6. The composition of claim 1, further comprising at least one growth factor to be delivered incorporated therein in a sufficient concentration to provide sustained release of said growth factor in addition to the sustained release of said protein.

7. A method of providing sustained release of proteins to a subject by administering to the subject a composition comprising a covalently cross-linked N,O-carboxymethyl chitosan hydrogel having a protein to be delivered incorporated therein in a sufficient concentration to provide said sustained release.

8. The method of claim 7, wherein said protein is selected from the group consisting of plasma proteins and osteogenic proteins.

9. The method of claim 8, wherein said plasma protein is selected from the group consisting of Factor IX, Factor VIII, and mixtures thereof.

10. The method of claim 7, wherein said subject has a plasma protein deficiency.

11. The method of claim 10, wherein said disorder is selected from the group consisting of Hemophilia B and Hemophilia A.

12. The method according to claim 7, wherein said composition further comprises a t least one growth facto r to be delivered incorporated therein in a sufficient concentration to provide sustained release of said growth factor.

13. The method according to claim 8, wherein said osteogenic protein comprises bone morphogenic protein.

14. A method of promoting wound healing comprising administering to the wound a composition comprising a covalently cross-linked N,O-carboxymethyl chitosan hydrogel having at least one therapeutically effective protein to be delivered incorporated therein in a sufficient concentration to provide said sustained release of said protein to said wound.

15. The method according to claim 14, wherein said composition administered to said wound further comprises a resorbable backing selected from the group consisting of proteinaceous substances and carbohydrate-derived substances.

16. The method according to claim 15, wherein said proteinaceous substances are selected from the group consisting of fibrin, collagen, keratin, and mixtures thereof.

17. The method according to claim 15, wherein said carbohydrate-derived substance is chitin.

18. The method according to claim 14, wherein said composition is in the form of an expandable foam.

19. The method according to claim 14, wherein said composition further comprises at least one growth factor to be delivered incorporated therein in a sufficient concentration to provide sustained delivery of said growth factor.

20. The method according to claim 19, wherein said wound is in a hard tissue.

21. The method according to claim 20, wherein said hard tissue is bone.

22. The method according to claim 21, wherein said protein comprises an osteogenic protein.

23. The method according to claim 22, wherein said osteogenic protein comprises a bone morphogenic protein.

24. The method according to claim 23, wherein said composition further comprises a bone growth promoting substance selected from the group consisting of bone marrow cells, bone chips, hydroxyapatite, and mixtures thereof.

25. A wound dressing composition for treatment of wounded tissue, said composition comprising a covalently cross-linked N,O-carboxymethyl chitosan hydrogel;

and a resorbable backing consisting essentially of therapeutically effective proteinaceous substances.

26. The composition according to claim 25, wherein said N,O-carboxymethyl chitosan hydrogel is in the form of a dry material which forms a N,O-carboxymethyl chitosan hydrogel upon hydration.

27. The composition according to claim 26, wherein said dry material comprises a freeze dried N,O-carboxymethyl chitosan hydrogel.

28. The composition of claim 25, wherein said proteinaceous substances are selected from the group consisting of fibrin, fibrinogen, collagen, keratin, and mixtures thereof.

29. The composition according to claim 25, which hydrogel further comprises a growth factor.

30. The composition of claim 26, further comprising a proteinaceous substance.

31. The composition of claim 30, wherein said wound is an internal wound.

32. The composition of claim 30, wherein said proteinaceous substance is selected from the group consisting of fibrin, fibrinogen, collagen, keratin, and mixtures thereof.