Methods of Augmenting or Repairing Soft Tissue

• US 20090117188A1
• Filed: 10/31/2008
• Published: 05/07/2009
• Est. Priority Date: 11/02/2007
• Status: Abandoned Application

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Gershkovich, Julia B., Monheit, Gary D., Jarrett, Peter K., Skinner, Kevin C.
• Application Number:
  US12/262,563
• Publication Number:
  US 20090117188A1
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 31/08 acyclic, e.g. paraformaldehyde
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08L 23/06 Polyethene

Abstract

Methods of repairing or augmenting soft tissue in a subject are described. The methods include injecting into a subject composition comprising a biodegradable, polymerizable macromer, the macromer comprising a water soluble polymer modified with one or more biodegradable moieties; and polymerizing the macromer to provide a hydrogel, thus repairing or augmenting the soft tissue.

Claims

1. A method of repairing or augmenting soft tissue in a subject, the method comprising

a. injecting into a subject in need thereof a composition comprising a biodegradable, polymerizable macromer, the macromer comprising a water soluble polymer modified with one or more biodegradable moieties;

and

b. polymerizing the macromer to provide a hydrogel wherein the hydrogel to soft tissue have a normalized compliance ratio of from about 0.05 to about 3, thus repairing or augmenting the soft tissue.

2. The method of claim 1, wherein the compliance ratio is from about 0.1 to about 2.0 relative to the soft tissue.

3. The method of claim 2, wherein the compliance ratio is from about 0.1 to about 1.0 relative to the soft tissue.

4. The method of claim 1, wherein the macromer is polymerized by irradiating through the skin of the subject with visible light.

5. The method of claim 1, wherein the subject is irradiated with visible light for from about 10 seconds to about 120 seconds.

6. The method of claim 5, wherein the subject is irradiated with visible light for at least about 30 seconds.

7. The method of claim 6, wherein the subject is irradiated with visible light for at least about 40 seconds.

8. The method of claim 1, wherein the macromer is polymerized by irradiating the subject with blue-green light.

9. The method of claim 1, wherein the macromer is polymerized by irradiating the subject with thermal energy.

10. The method of claim 1, wherein the water soluble polymer is PEG.

11. The method of claim 10, wherein the PEG has a molecular weight of from about 10,000 to about 35,000 Daltons.

12. The method of claim 1, wherein the water soluble polymer is a block-copolymer.

13. The method of claim 12, wherein the block-copolymer is an ethyleneoxide and propyleneoxide.

14. The method of claim 1, wherein the macromer is biodegradable.

15. The method of claim 1, wherein the macromer comprises a plurality of hydrolysable linkages.

16. The method of claim 15, wherein the hydrolyzable linkages are selected from the group consisting of esters or carbonates.

17. The method of claim 1, wherein the water soluble polymer is modified with an acrylate-capped poly (L-lactide).

18. The method of claim 17, wherein the water soluble polymer is PEG.

19. The method of claim 1, wherein the water soluble polymer is modified with a poly (trimethylene carbonate).

20. The method of claim 19, wherein the water soluble polymer is PEG.

21. The method of claim 1, wherein the water soluble polymer is modified with an poly (L-lactide) and poly (trimethylene carbonate) and an acrylate endcap.

22. The method of claim 21, wherein the water soluble polymer is PEG.

23. The method of claim 1, wherein the composition further comprises a photo-initiator.

24. The method of claim 23, wherein the photoinitiator is a dye.

25. The method of claim 24, wherein the dye is eosin.

26. The method of claim 1, wherein the composition further comprises a rheology modifier.

27. The method of claim 26, wherein the rheology modifier is HA or CMC.

28. The method of claim 1, wherein the composition is substantially free of organic solvent.

29. The method of claim 1, wherein the hydrogel has a strain or elongation before fracture substantially similar to the expected strain during normal use of the soft tissue to which it augments or repairs.

30. The method of claim 1, wherein the hydrogel has a strain or elongation before fracture greater than the expected strain during normal use of the soft tissue to which it augments or repairs.

31. The method of claim 1, wherein the hydrogel has a reversible elongation at least about 150% as great as an expected strain of the soft tissue which is augments or repairs.

32. The method of claim 1, wherein the hydrogel has an elastic modulus which is less than about 150 kPa.

33. The method of claim 1, wherein the hydrogen has an ultimate yield stress of from about 500 to about 2,000 psi.

34. The method of claim 1, wherein the macromer is injected subdermally.

35. The method of claim 34, wherein the macromer is polymerized by irradiating least a part of the skin of the subject.

36. The method of claim 35, wherein the skin is irradiated for at least about 30 seconds.

37. The method of claim 1, wherein the macromer is injected intradermally.

38. The method of claim 37, wherein the macromer is polymerized by irradiating at least a part of the skin of the subject.

39. The method of claim 38, wherein the skin is irradiated for at least about 30 seconds.

40. The method of claim 1, further comprising shaping the macromer.

41. The method of claim 40, wherein the macromer is shaped during polymerization of the macromer.

42. The method of claim 41, wherein the macromer is polymerized by irradiating through the skin of the subject.

43. The method of claim 1, comprising repeating steps a) and b) of claim 1 at least one time.

44. The method of claim 1, comprising repeating steps a) and b) of claim 1 at least two times.

45. The method of claim 1, wherein the subject is a mammal.

46. The method of claim 45, wherein the subject is a human.

47. The method of claim 1, the method comprising repairing facial tissue.

48. The method of claim 47, the method comprising decreasing the appearance of at least one facial line, wrinkle, crease, or fold.

49. The method of claim 1, the method comprising augmenting breast, lip, cheek, chin, forehead, buttocks, hand, neck or earlobe tissue in a subject.

50. The method of claim 1, the method comprising decreasing the appearance of a dermal dimple.

51. The method of claim 50, wherein the dimple is a component of a scar.

52. The method of claim 1, wherein the composition is administered with a red tinted syringe.

53. The method of claim 1, wherein the soft tissue remains substantially augmented or repaired for at least about 1 month.

54. The method of claim 53, wherein the soft tissue remains substantially augmented or repaired for at least about 2 months.

55. The method of claim 54, wherein the soft tissue remains substantially augmented or repaired for at least about 6 months.

56. The method of claim 1, wherein the hydrogel elicits a mild fibrotic response in the subject.

57. The method of claim 1, wherein the composition comprises a two part system, and wherein the polymerization is initiated via a redox system.

58. The method of claim 57, wherein the polymerization occurs over a period of from about 30 seconds to about 2 minutes.

59. The method of claim 1, wherein the composition further comprises a drug such as an non-steroidal anti-inflammatory, an analgesic, a vitamin such as E, C, A, D or K, an anti-oxidant, an alpha hydroxyl acid such as lactic acid or a polymer capable of releasing such drug, vitamin, anti oxidant or alpha-hydroxyacid or any combination thereof.