Polyurethane-grafted hydrogels

• US 8,497,023 B2
• Filed: 08/05/2009
• Issued: 07/30/2013
• Est. Priority Date: 08/05/2008
• Status: Expired due to Fees

• Current Assignee: Biomimedica, Inc, Emergence Venture Partners, LLC
• Original Assignee: Biomimedica, Inc, Emergence Venture Partners, LLC
• Inventors: Myung, David, Kourtis, Lampros, Ward, Robert, Jaasma, Michael J., McCrea, Keith
• Primary Examiner(s): Tran, Thao T.
• Application Number:
  US12/536,233
• Publication Number:
  US 20100032090A1
• Time in Patent Office: 1,455 Days
• Field of Search: 428/423.1, 428/424.7, 424/425, 514/16.7, 514/17.1, 514/17.2, 523/115
• US Class Current: 428/423.1
• CPC Class Codes: A61K 6/893 Polyurethanes
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: B32B 2037/243 Coating
• CPC Class Codes: B32B 2375/00 Polyureas; Polyurethanes
• CPC Class Codes: B32B 2535/00 Medical equipment, e.g. bandage, prostheses, catheter medical patches B32B2556/00
• CPC Class Codes: C08F 283/02 on to polycarbonates or saturated polyesters C08F283/004 takes precedence
• CPC Class Codes: C08G 18/44 Polycarbonates
• CPC Class Codes: C08G 18/664 with compounds of group C08G18/3203
• CPC Class Codes: C08G 18/672 Esters of acrylic or alkyl acrylic acid having only one group containing active hydrogen
• CPC Class Codes: C08G 2210/00 Compositions for preparing hydrogels
• CPC Class Codes: C08G 2270/00 Compositions for creating interpenetrating networks
• CPC Class Codes: C08J 2375/04 Polyurethanes
• CPC Class Codes: C08J 9/36 After-treatment C08J9/22 takes precedence
• CPC Class Codes: C08L 2666/04 Macromolecular compounds according to groups C08L7/00 - C08L49/00, or C08L55/00 - C08L57/00; Derivatives thereof
• CPC Class Codes: C08L 75/02 : Polyureas
• CPC Class Codes: C08L 75/16 : having terminal carbon-to-carbon unsaturated bonds
• CPC Class Codes: Y10T 428/31551 : Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]
• CPC Class Codes: Y10T 428/31583 : Nitrile monomer type [polyacrylonitrile, etc.]

Abstract

An article comprising two chemically grafted polymer layers comprising a hydrogel layer and an end-functionalized polyurethane layer. The invention also includes methods of making and using the article.

Claims

1. An article comprising two chemically grafted polymer layers comprising a hydrogel layer and an end-functionalized polyurethane layer, wherein the hydrogel layer is covalently linked to the end-functionalized polyurethane layer at an interface between the two layers.

2. The article of claim 1 wherein the polyurethane comprises polycarbonate urethane, polycarbonate urethane urea, polyester urethane, polyether urethane, polyurethane urea, or a silicone derivative of these.

3. The article of claim 1 wherein the polyurethane comprises hard and soft segments, chain extenders and endgroups.

4. The article of claim 3 wherein the polyurethane hard segments comprise 1,5 naphthalene diisocyanate (NDI), isophorone isocyanate (IPDI), 3,3-bitoluene diisocyanate (TODI), methylene bis(p-cyclohexyl isocyanate) (H12MDI), cyclohexyl diiscocyanate (CHDI), 2,6 tolulene diisocyanate or 2,4 toluene diisocyanate (TDI), hexamethyl diisocyanate (HMDI), or methylene bis(p-phenyl isocyanate) (MDI).

5. The article of claim 3 wherein the polyurethane soft segments comprise hydroxy terminated butadiene, hydroxyl terminated polyisobutylene, hydroxybutyl terminated polydimethylsiloxane (PDMS), poly(1,6 hexyl 1,2-ethyl carbonate), hydrogenated polybutadiene, polycaprolactone, polyethylene adipate, polyethylene oxide (PEO), polyhexamethylene carbonate glycol, polypropylene oxide (PPO), polytetramethylene adipate, or poly(tetramethylene oxide) (PTMO).

6. The article of claim 3 wherein the polyurethane chain extenders comprise 1,4 butanediol, ethylene diamine, 4,4′

methylene bis(2-chloroaniline) (MOCA), ethylene glycol, or hexane diol.

7. The article of claim 3 wherein the polyurethane endgroups comprise acylamide, acrylate, allyl ether, methacrylate, or vinyl.

8. The article of claim 1 wherein the hydrogel comprises end-linked macromeric subunits.

9. The article of claim 8 wherein the macromeric subunits are PEG.

10. The article of claim 1 wherein the hydrogel comprises a biomolecule.

11. The article of claim 10 wherein the biomolecule comprises collagen, one or more growth factors, steroids, bisphosphonates, or combinations or derivatives thereof.

12. The article of claim 11 wherein the growth factors comprise one or more of a Bone Morphogenetic Protein, a Fibroblast Growth Factor, a Transforming Growth Factor, or a Osteogenic Protein.

13. The article of claim 1 wherein the hydrogel comprises a homopolymer.

14. The article of claim 1 wherein the hydrogel comprises polymerized monomeric subunits.

15. The article of claim 1 wherein the hydrogel comprises a copolymer.

16. The article of claim 15 wherein the copolymer comprises polymerized subunits.

17. The article of claim 16 wherein the subunits are one or more of acrylamide, hydroxyethyl acrylamide, N-isopropyl acrylamide, 2-hydroxyethyl methacrylate, and 2-hydroxyethyl acrylate.

18. The article of claim 15 wherein at least 50% of the dry weight of hydrogel comprises telechelic macromonomer.

19. The article of claim 15 wherein at least 75% of the dry weight of hydrogel comprises telechelic macromonomer.

20. The article of claim 15 wherein at least 95% of the dry weight of hydrogel comprises telechelic macromonomer.

21. The article of claim 1 wherein the hydrogel comprises an IPN comprising a first and a second network.

22. The article of claim 21 wherein the first network comprises polymerized macromeric subunits.

23. The article of claim 22 wherein the macromeric subunit comprises PEG, poly(N-vinyl pyrrolidone), polydimethylsiloxane, poly(vinyl alcohol), polysaccharide, or a biomolecule.

24. The article of claim 22 wherein the macromeric subunit comprises end group or side group functionalities, said end group or side group functionalities comprising at least one of acrylamide, acrylate, allyl, methacrylamide, methacrylate, N-vinyl sulfone, and vinyl.

25. The article of claim 21 wherein the second network comprises polymerized subunits.

26. The article of claim 25 wherein the second network is hydrophilic.

27. The article of claim 26 wherein the second network is ionizable.

28. The article of claim 27 wherein the ionizable network is anionic.

29. The article of claim 28 wherein the subunits of the anionic second network comprise at least one of carboxylic acid and sulfonic acid groups.

30. The article of claim 28 wherein the anionic second network is polyacrylic acid.

31. The article of claim 28 wherein the ionizable network is cationic.

32. The article of claim 26 wherein the hydrophilic network is non-ionic.

33. The article of claim 32 wherein the subunits of the non-ionic network comprise one or more of acrylamide, methacrylamide, N-hydroxyethyl acrylamide, N-isopropylacrylamide, methymethacrylate, N-vinyl pyrrolidone, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, or derivatives of these.

34. The article of claim 21 wherein both networks are grafted to the polyurethane.

35. The article of claim 1 further comprising a second polyurethane attached to the first polyurethane.

36. The article of claim 35 wherein the second polyurethane comprises functionalized end groups.

37. The article of claim 35 wherein the second polyurethane comprises salt.

38. The article of claim 35 wherein the second polyurethane is porous.

39. The article of claim 35 wherein the second polyurethane comprises a foaming agent.

40. The article of claim 35 wherein the second polyurethane further comprises a biomolecule.

41. The article of claim 40 wherein the biomolecule comprises at least one of collagen, bone morphogenetic protein, bisphosphonate, and an osteogenic protein.

42. The article of claim 35 wherein the second polyurethane further comprises a bone component.

43. The article of claim 42 wherein the bone component is one of at least carbonated apatite, hydroxyapatite, alpha tricalcium phosphate, beta tricalcium phosphate, and other calcium phosphates.

44. The article of claim 1 further comprising entrapped fillers.

45. The article of claim 1 further comprising an antioxidant.

46. The article of claim 45 wherein the antioxidant is selected from the group consisting of ascorbic acid, Vitamin E, Irganox®

, santowhite, glutathione, uric acid, lipoic acid, beta carotene, retinol, and ubiquinol.