Compositions containing polyanionic polysaccharides and hydrophobic bioabsorbable polymers

• US 6,703,041 B2
• Filed: 09/04/2001
• Issued: 03/09/2004
• Est. Priority Date: 10/06/1994
• Status: Expired due to Fees

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: Burns, James W., Greenawalt, Keith E., Masi, Louis
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US09/946,121
• Publication Number:
  US 20020018813A1
• Time in Patent Office: 917 Days
• Field of Search: 424/488, 424/443-44, 424/426, 424/400, 424/402, 514/777, 514/54
• US Class Current: 424/444
• CPC Class Codes: A61B 90/00 Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges protective face masks A41D13/11; surgeon's or patient's gowns or dresses A41D13/12; devices for carrying-off, for treatment of, or for carrying-over, body liquids A61M1/00
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C08L 1/28 Alkyl ethers
• CPC Class Codes: C08L 5/00 Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 5/10 Heparin; Derivatives thereof
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Biocompatible compositions comprising polyanionic polysaccharides combined with hydrophobic bioabsorbable polymers as well as methods for making and using the compositions are described.

Claims

1. A water-insoluble biocompatible composition comprising a water-insoluble derivative of a first polyanionic polysaccharide and fibers of a hydrophobic bioabsorbable polymer, wherein the derivative is formed by reacting the polyanionic polysaccharide at least with an activating agent to form a derivative bearing i) an amide or amine group or ii) N-acyl urea group.

2. The composition of claim 1 wherein said derivative is formed by reacting the polyanionic polysaccharide with an activating agent and a nucleophile.

3. The composition of claim 1, wherein said polyanionic polysaccharide is chosen from the group consisting of carboxymethylcellulose, carboxymethylamylose, hyaluronic acid, chondroitin-6-sulfate, heparin, heparin sulfate, and dermatan sulfate.

4. The composition of claim 3, wherein said polyanionic polysaccharide is carboxymethylamylose.

5. The composition of claim 3, wherein said polyanionic polysaccharide is carboxymethylcellulose.

6. The composition of claim 3 wherein said polyanionic polysaccharide is hyaluronic acid.

7. The composition of claim 1 wherein said biocompatible composition comprises two or more a water-insoluble derivative of a second polyanionic polysaccharides.

8. The composition of claim 7 wherein first and second polyanionic polysaccharides are hyaluronic acid and carboxymethylcellulose.

9. The composition of claim 1, wherein said hydrophobic bioabsorbable polymer is chosen from the group consisting of polyglycolide, polylactide, polydioxanones, polyestercarbonates, polyhydroxyalkonates, polylactones, and copolymers thereof.

10. The composition of claim 9 wherein said hydrophobic bioabsorbable polymer is polyglycolide.

11. The composition of claim 9 wherein said hydrophobic bioabsorbable polymer is polylactide.

12. The composition of claim 9 wherein said hydrophobic bioabsorbable polymer is a copolymer of polyglycolide and polylactide.

13. The composition of claim 9 wherein said hydrophobic bioabsorbable polymer is a copolymer of polyglycolide/polycaprolactone.

14. The composition of claim 9 wherein said hydrophobic bioabsorbable polymer is a copolymer of polylactide/polycaprolactone.

15. The composition of claim 1, wherein said composition is in the form of a membrane.

16. The composition of claim 1, wherein said composition is in the form of a foam.

17. The composition of claim 1 wherein said form a mesh or matte.

18. The composition of claim 1, further comprising a drug.

19. The composition of claim 18 wherein said drug is chosen from the group consisting of proteins, biopolymers, steroids, non-steroidal anti-inflammatory drugs, cytotoxic agents, antibiotics, and oligonucleotides.

20. The composition of claim 7, further comprising a drug.

21. The composition of claim 20, wherein said drug is chosen from the group consisting of proteins, biopolymers, steroids, non-steroidal anti-inflammatory drugs, cytotoxic agents, antibiotics, and oligonucleotides.

22. The composition of claim 1 further comprising biological cells.

23. The composition of claim 22, wherein said composition is admixed with said cells.

24. The composition of claim 22, wherein said composition is infiltrated with said cells.

25. The composition of claim 22, wherein said cells are derived from a mammal.

26. The composition of claim 25, wherein said mammal is a human.

27. The composition of claim 22, wherein said cells comprise fibroblasts.

28. The composition of claim 22, wherein said cells comprise osteocytes.

29. The composition of claim 22, wherein said cells comprise chondrocytes.

30. The composition of claim 22, wherein said cells comprise keratinocytes.

31. The composition of claim 22, wherein said cells comprise tenocytes.

32. The composition of claim 22, wherein said cells comprise non-differentiated mesenchymal cells.

33. The composition of claim 22, wherein said cells comprise a mixture of at least two cell types.

34. The composition of claim 22, further comprising a drug.

35. The composition of claim 34, wherein said drug is a growth factor.

36. The composition of claim 34 wherein said drug is an antibiotic.

37. The composition of claim 7, further comprising biological cells.

38. The composition of claim 37, wherein said composition is admixed with said cells.

39. The composition of claim 37, wherein said composition is infiltrated with said cells.

40. The composition of claim 37, wherein said cells are derived from a mammal.

41. The composition of claim 40, wherein said mammal is a human.

42. The composition of claim 37, wherein said cells comprise fibroblasts.

43. The composition of claim 37, wherein said cells comprise osteocytes.

44. The composition of claim 37, wherein said cells comprise chondrocytes.

45. The composition of claim 37, wherein said cells comprise keratinocytes.

46. The composition of claim 37, wherein said cells comprise tenocytes.

47. The composition of claim 37, wherein said cells comprise non-differentiated mesenchymal cells.

48. The composition of claim 37, wherein said cells comprise a mixture of at least two cell types.

49. The composition of claim 37, further comprising a drug.

50. The composition of claim 49, wherein said drug is a growth factor.

51. The composition of claim 49, wherein said drug is an antibiotic.

52. The composition of claim 1 wherein said activating agent is a carbodiimide.

53. The composition of claim 52 wherein said carbodiimide is 1-(-3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC).

54. The composition of claim 52 wherein said carbodiimide is 1-(-3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (ETC).

55. The composition of claim 7 wherein said second water-insoluble polyanionic polysaccharide is formed by reacting the second polyanionic polysaccharide with an activating agent.

56. The composition of claim 55 wherein said activating agent is a carbodiimide.

57. The composition of claim 56 wherein said carbodiimide is 1-(-3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC).

58. The composition of claim 56 wherein said carbodiimide is 1-(-3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (ETC).

59. An article comprising the composition of claim 1 wherein the fibers form a mesh or matte.

60. The article of claim 59 having the shape of a sheet.

61. The article of claim 59 having the shape of a tube.