SURGICAL HYDROGEL

• US 20100291055A1
• Filed: 08/26/2008
• Published: 11/18/2010
• Est. Priority Date: 08/28/2007
• Status: Abandoned Application

• Current Assignee: Medtronic Xomed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Xomed Incorporated (Medtronic Plc)
• Inventors: Shi, Zheng, Simpson, James, Robinson, Brian Harford, Wormald, Peter John, Athanasiadis, Theodore, Moratti, Stephen Carl, Hanton, Lyall Robert, Robinson, Simon Rae
• Application Number:
  US12/675,329
• Publication Number:
  US 20100291055A1
• Time in Patent Office: Days
• US Class Current: 424/94.1
• CPC Class Codes: A61K 31/738 Cross-linked polysaccharides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 2400/04 Materials for stopping bleeding
• CPC Class Codes: A61L 26/0052 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: C08B 37/0063 Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

The invention provides a hydrogel suitable for use in wound healing, particularly for reducing post-surgical adhesions. The hydrogel comprises cross-linked derivatives of chitosan and dextran polymers. The hydrogel forms when solutions of the polymers are combined.

Claims

1. A composition comprising a dicarboxy-derivatised chitosan polymer cross-linked to an aldehyde-derivatized dextran polymer.

2. The composition as claimed in claim 1 wherein the dicarboxy-derivatised chitosan polymer is cross-linked to the aldehyde-derivatised dextran polymer through the amine group of the dicarboxy-derivatised chitosan polymer and the aldehyde group of the aldehyde-derivatised dextran polymer.

3. The composition as claimed in claim 1 or claim 2 wherein the polymer network forms a hydrogel within about 1 sec to about 5 minutes of mixing the dicarboxy-derivatised chitosan polymer and the aldehyde-derivatised dextran polymer in aqueous solution.

4. The composition as claimed in claim 3 wherein the polymer network forms a hydrogel within about 1 sec to about 30 sec of mixing the dicarboxy-derivatised chitosan polymer and the aldehyde-derivatised dextran polymer in aqueous solution.

5. The composition as claimed in claim 1 wherein the dicarboxy-derivatised chitosan polymer is N-succinyl chitosan.

6. The composition of claim 1, further comprising an aqueous solution.

7. The composition of claim 6 wherein the composition comprises between about 2% to 10% w/v dicarboxy-derivatised chitosan polymer and between about 2% to 10% w/v aldehyde-derivatised dextran polymer.

11. The composition of claim 7 comprising between about 2% to about 8% w/v dicarboxy-derivatised chitosan polymer and about 2% to about 8% w/v aldehyde-derivatised dextran polymer.

12. The composition of claim 7 comprising about 5% w/v dicarboxy-derivatised chitosan polymer and about 5% w/v aldehyde-derivatised dextran polymer.

21. The composition of claim 1, further comprising one or more biologically active agents.

22. The composition of claim 21 wherein said one or more biologically active agents are selected from the group consisting of plasma proteins, hormones, enzymes, antibiotics, antiseptic agents, antineoplastic agents, antifungal agents, antiviral agents, anti-inflammatory agents, growth factors, steroids, cell suspensions, cytotoxins, and cell proliferation inhibitors.

23. A method of preventing or reducing adhesion of tissue susceptible to adhesion formation comprising treating the tissue with a composition of claim 1.

24. The method of claim 23 wherein the adhesion is a post-surgical adhesion.

25. A method of accelerating or promoting wound healing comprising treating the wound with a composition of claim 1.

26. A method of reducing or stopping bleeding of a wound comprising treating the wound with a composition of claim 1.

38. A wound dressing comprising the composition of claim 1.

8-10. -10. (canceled)

13. (canceled)

14. A method of producing composition of a dicarboxy-derivatised chitosan polymer cross-linked to an aldehyde-derivatised dextran polymer, comprising:

mixing an aqueous solution of a dicarbosy-derivatised chitosan polymer with an aqueous solution of an aldehyde-derivatised aldehyde dextran polymer.

15. A The method of claim 14 wherein the aqueous solution of a dicarboxy-derivatised chitosan polymer is between about 2% to about 10% w/v and the aqueous solution of dicarboxy-derivatised dextran polymer is between about 2% to about 10% w/v.

18. The method of claim 14 wherein the pH of each aqueous solution is between about 6 to about 8.

20. The method of claim 14 wherein the dicarboxy-derivatised chitosan polymer is N-succinyl chitosan.

16-17. -17. (canceled)

19. (canceled)

27-28. -28. (canceled)

29. A method of treating a tissue comprising applying to said tissue:

(a) an aqueous solution of a dicarboxy-derivatised chitosan polymer; and

(b) an aqueous solution of an aldehyde-derivatised dextran polymer, such that (a) and (b) combine to form a cross-linked composition on said tissue.

30. The method of claim 29, wherein said tissue has been injured.

31. The method of claim 30, wherein said injury is selected from the group consisting of wound, surgery or results in bleeding.

32. The method of claim 29, wherein said step of applying is selected from the group consisting of spraying, squirting or pouring.

33. The method of claim 29 wherein (a) and (b) are simultaneously applied to said tissue.

35. The method of claim 29 wherein cross-linked composition forms within about 1 sec to about 5 minutes of combining (a) and (b).

37. The method of claim 29 wherein the dicarboxy-derivatised chitosan polymer is N-succinyl chitosan.

34. (canceled)

36. (canceled)

39. A kit comprising:

(a) dicarboxy-derivatised chitosan polymer, and

(b) an aldehyde-derivatized dextran polymer.

40. The kit as claimed in claim 39 wherein (a) and (b) are freeze-dried.

41. The kit as claimed in claim 39 wherein either or both of (a) and (b) are provided in separate aqueous solutions.

42. The kit of claim 41 wherein the aqueous solution of (a) is between about 2% to about 10% w/v and the aqueous solution of (b) is between about 2% to about 10% w/v.

43. A The kit of claim 42 wherein the aqueous solutions comprise between about 0.1% to about 2% w/v NaCl.

44. The kit of claim 39 additionally comprising an aqueous solution in which (a) and (b) can be dissolved to allow cross-linking to occur.

45. The kit of claim 39 wherein (a) is N-succinyl chitosan.