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1. WO2016149615 - POLYPEPTIDE COMPOSITIONS AND METHODS OF USING THE SAME

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[ EN ]

CLAIMS

What is claimed is:

1. A polypeptide comprising an amino acid sequence of {[VPGVG]4lPGVG}n, wherein n is an integer greater than 1.

2. The polypeptide of claim 1, wherein n is in the range of 10-28.

3. The polypeptide of claim 1, wherein n is in the range of 10-14.

4. The polypeptide of claim 1, wherein n is 14.

5. The polypeptide of any one of claims 1-4, further comprising a first cysteine-containing peptide linked to a first side of the amino acid sequence of {[VPGVG]4IPGVG}n.

6. The polypeptide of claim 5, further comprising a second cysteine-containing peptide linked to a second side of the amino acid sequence of {[VPGVG]4IPGVG}n.

7. The polypeptide of claim 5, wherein the first cysteine-containing peptide comprises an amino acid sequence of KCTS.

8. The polypeptide of claim 6, wherein the second cysteine-containing peptide comprises an amino acid sequence of KCTS.

9. The polypeptide of any one of claims 1-8, further comprising an amino acid sequence of RGD.

10. A composition comprising a polypeptide of any one of claims 1-9 and a photoinitiator.

11. The composition of claim 10, wherein the photoinitiator is selected from the group

consisting of l-[4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-l-propane-l-one, 1- hydroxycyclohexyl phenyl ketone, 2-benzyl-2,N,N-dimethylamino-l-(4- morpholinophenyl)-l-butanone, 2-hydroxy-2-methyl-l -phenyl propane- 1 -one, 2,2- dimethoxy-2- phenyl acetophenone, and Eosin Y.

12. A kit comprising a polypeptide of any one of claims 1-9 and a photoinitiator.

13. The kit of claim 12, wherein the photoinitiator is selected from the group consisting of 1- [4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl- 1 -propane- 1 -one, 1 - hydroxycyclohexyl phenyl ketone, 2-benzyl-2,N,N-dimethylamino-l-(4- morpholinophenyl)-l-butanone, 2-hydroxy-2-methyl-l -phenyl propane- 1 -one, 2,2- dimethoxy-2- phenyl acetophenone, and Eosin Y.

14. A hydrogel comprising a polypeptide comprising an amino acid sequence of

{ [VPGVG]4IPGVG}n, wherein n is an integer greater than 1.

15. The hydrogel of claim 14, wherein n is in the range of 10-28.

16. The hydrogel of claim 14, wherein n is in the range of 10-14.

17. The hydrogel of claim 14, wherein n is 14.

18. The hydrogel of any one of claims 14-17, wherein the polypeptide further comprises a first cysteine-containing peptide linked to a first side of the amino acid sequence of { [VPGVG]4IPGVG}n.

19. The hydrogel of claim 18, wherein the polypeptide further comprises a second cysteine- containing peptide linked to a second side of the amino acid sequence of

{ [VPGVG]4IPGVG}n.

20. The hydrogel of claim 18, wherein the first cysteine-containing peptide comprises an amino acid sequence of KCTS.

21. The hydrogel of claim 19, wherein the second cysteine-containing peptide comprises an amino acid sequence of KCTS.

22. The hydrogel of any one of claims 14-21, wherein the polypeptide further comprises an amino acid sequence of RGD.

23. The hydrogel of any one of claims 14-22, wherein the polypeptide is present at a

concentration between 5% and 30% (w/v).

24. The hydrogel of any one of claims 14-22, wherein the polypeptide is present at a

concentration between 10% and 30% (w/v).

25. The hydrogel of any one of claims 14-22, wherein the polypeptide is present at a

concentration between 10% and 20% (w/v).

26. The hydrogel of any one of claims 14-25, having extensibility up to 500%.

27. The hydrogel of any one of claims 14-25, having extensibility up to 450%.

28. The hydrogel of any one of claims 14-25, having extensibility up to 400%).

29. The hydrogel of any one of claims 14-28, having an elastic modulus in the range of 0.5- lOkPa.

30. The hydrogel of any one of claims 14-28, having an elastic modulus in the range of 1- 5kPa.

31. The hydrogel of any one of claims 14- -28, having an elastic modulus in the range of 1- 2.5kPa.

32. The hydrogel of any one of claims 14-31, having a tensile strength in the range of 4 to

20kPa.

33. The hydrogel of any one of claims 14-31, having a tensile strength in the range of 5 to

15kPa.

34. The hydrogel of any one of claims 14-31, having a tensile strength in the range of 6 to

12kPa.

35. The hydrogel of any one of claims 14-34, having a compressive modulus of 1 to 20kPa.

36. The hydrogel of any one of claims 14-34, having a compressive modulus of 2 to 18kPa.

37. The hydrogel of any one of claims 14-34, having a compressive modulus of 3 to 15kPa.

38. The hydrogel of any one of claims 14- -37, further comprising a hemostatic agent selected from the group consisting of silica nanoparticles, blood coagulation factors, prothrombin, thrombin, fibrinogen, fibrin, gelatin, collagen, polysaccharide, and cellulose.

39. The hydrogel of any one of claims 14-38, further comprising an antibacterial agent

selected from the group consisting of silver nanoparticles, copper oxide nanoparticles, nanoparticle-carried antibiotic drugs, penicillins, cephalosporins, penems, carbapenems, monobactams, aminoglycosides, sulfonamides, macrolides, tetracyclins, lincosides, quinolones, chloramphenicol, vancomycin, metronidazole, rifampin, isoniazid, spectinomycin, trimethoprim, and sulfamethoxazole.

40. The hydrogel of any one of claims 14-39, further comprising one or more biological cells.

41. The hydrogel of any one of claims 14-40, wherein the hydrogel is biocompatible.

42. The hydrogel of any one of claims 14-41, produced by crosslinking the polypeptide in the presence of a photoinitiator under light irradiation.

43. The hydrogel of claim 42, wherein the photoinitiator is selected from the group consisting of 1 -[4-(2 -Hydroxy ethoxy)-phenyl]-2-hydroxy-2-methyl- 1 -propane- 1 -one, 1 - hydroxycyclohexyl phenyl ketone, 2-benzyl-2,N,N-dimethylamino-l-(4- morpholinophenyl)-l-butanone, 2-hydroxy-2-methyl-l -phenyl propane- 1 -one, 2,2- dimethoxy-2- phenyl acetophenone, and Eosin Y.

44. The hydrogel of claim 42 or 43, wherein the light is ultraviolet or visible.

45. A tissue scaffold comprising a hydrogel of any one of claims 14-44 and at least one biological cell.

46. The tissue scaffold of claim 45, comprising at least two types of biological cells.

47. The tissue scaffold of claim 45 or 46, promoting tissue ingrowth.

48. A method of treating bleeding, the method comprising contacting a bleeding site with a hydrogel comprising (a) a polypeptide comprising an amino acid sequence of

{[VPGVG]4lPGVG}n, wherein n is an integer greater than 1; and (b) a hemostatic agent.

49. The method of claim 48, wherein the hemostatic agent is selected from the group

consisting of silica nanoparticles, blood coagulation factors, prothrombin, thrombin, fibrinogen, fibrin, gelatin, collagen, polysaccharide, and cellulose.

50. The method of claim 48 or 49, wherein n is in the range of 10-28.

51. The method of claim 48 or 49, wherein n is in the range of 10-14.

52. The method of claim 48 or 49, wherein n is 14.

53. The method of any one of claims 48-52, wherein the polypeptide further comprises a first cysteine-containing peptide linked to a first side of the amino acid sequence of

{[VPGVG]4IPGVG}n.

54. The method of claim 53, wherein the polypeptide further comprises a second cysteine- containing peptide linked to a second side of the amino acid sequence of

{[VPGVG]4IPGVG}n.

55. The method of claim 53, wherein the first cysteine-containing peptide comprises an

amino acid sequence of KCTS.

56. The method of claim 54, wherein the second cysteine-containing peptide comprises an amino acid sequence of KCTS.

57. The method of any one of claims 48-56, wherein the polypeptide further comprises an amino acid sequence of RGD.

58. The method of any one of claims 48-57, wherein the polypeptide is present in the

hydrogel at a concentration between 5% and 30% (w/v).

59. The method of any one of claims 48-57, wherein the polypeptide is present in the

hydrogel at a concentration between 10% and 30% (w/v).

60. The method of any one of claims 48-57, wherein the polypeptide is present in the

hydrogel at a concentration between 10% and 20% (w/v).

61. Use of a hydrogel of any one of claims 14-44 for the treatment of an injury in a soft and elastic tissue.

62. The use of claim 61, wherein the soft and elastic tissue is selected from the group

consisting of a blood vessel, skin, lung, cartilage, nucleus pulposus, bladder, and a cardiac tissue.

63. The use of claim 61 or 62, wherein the hydrogel functions as a sealant, filler, adhesive, coating, or growth-factor carrier.

64. A kit comprising a polypeptide of any one of claims 1-9 and a 4-arm polyethylene glycol.