IP Library Granted Patent US 10,201,634
Granted Patent B2
US 10,201,634 · App. 14/311,509 · Granted Feb 12, 2019

Nanotubes and compositions thereof

Inventors: Thomas J. Webster (Barrington, RI); Hicham Fenniri (Edmonton, CA); Usha Devi Hemraz (Edmonton, CA)
Assignees: Brown University; National Research Council of Canada; The Governors of the University of Alberta
A61L27/34A61L27/22A61L27/54C07D519/00A61L2400/12A61L2400/18
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Quick Facts
Patent No.
US 10,201,634
App. No.
14/311,509
Granted
Feb 12, 2019
Kind
B2
Abstract

The present invention is directed to implants and the modification of the surface of implants using amino acid or polypeptide functionalized rosette nanotubes.

Claims (81)

1. A method of promoting osteoblast differentiation and proliferation at a site of a bone injury or defect or bone surgical site comprising providing an implant having a composition including nanotubes formed from modules according to Formula II, nanoparticles, and a matrix material, and optionally nanotubes formed from modules according to Formula I, wherein Formula II is

having G^C motifs wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and

wherein Formula I is

wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and placing the implant at the site of a bone injury or defect or bone surgical site, wherein osteoblast differentiation and proliferation is promoted by the G^C motifs

wherein the linker is NH 3 + ,

(CH 2 ) 3 CO or (CH 2 ) n CH 3 where n is an integer of 0, 1, 2, or 3.

2. The method of claim 1 where R 1 is C 1 to C 10 alkyl, straight or branched chain, saturated or unsaturated.

3. The method of claim 1 wherein the nanoparticles are nanoparticles of calcium phosphate, hydroxyapatite, apatite, oxyapatite, octacalcium phosphate, monocalcium phosphate, dicalcium phosphate, tricalcium phosphate, β-tricalcium phosphate, α-tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate or calcium dihydrogen phosphate.

4. The method of claim 1 wherein the matrix material is one or more of polylactic acid, polylactide-coglycolide, polyglycolic acid, polymethylmethacrylate, polyurethane, polycaprolactone, polyethylene, polystyrene, polypropylene, polypyrrole, or poly(2-hydroxyethyl methacrylate).

5. The method of claim 1 wherein Formula I is absent, X is N, R 1 is methyl, R 2 is (CH 2 ) 3 CO, the nanoparticles are nanoparticles of hydroxyapatite, and the matrix material is poly(2-hydroxyethylmethacrylate).

6. A compound having the formula

wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and salts thereof,

wherein the linker is NH 3 + ,

(CH 2 ) 3 CO or (CH 3 ) n CH 3 where n is an integer of 0, 1, 2, or 3.

7. A compound having the formula

wherein X is CH or nitrogen; n is an integer of 0, 1, 2, 3, or 4; Y is absent; and R 1 is C1 to C10 alkyl, straight or branched chain, saturated or unsaturated; and salts thereof.

8. A structure formed from the self-assembly in aqueous media of compounds having the formula

wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and salt thereof,

wherein the linker is NH 3 + ,

(CH 2 ) 3 CO or (CH 3 ) n CH 3 where n is an integer of 0, 1, 2, or 3.

9. A structure formed from the self-assembly in aqueous media of compounds having the formula

wherein X is CH or nitrogen; n is an integer of 0, 1, 2, 3, or 4; Y is absent; and R 1 is C1 to C10 alkyl, straight or branched chain, saturated or unsaturated; and salts thereof.

10. A structure formed from the self-assembly in aqueous media of one or more compounds having the formula

wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and salt thereof,

and one or more compounds having the formula

wherein X is CH or nitrogen; n is an integer of 0, 1, 2, 3, or 4; Y is absent; and R 1 is C1 to C10 alkyl, straight or branched chain, saturated or unsaturated; and salts thereof.

11. A method of forming a nanotube comprising placing in an aqueous media compounds having the formula

wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and salt thereof, and at a sufficient concentration that a nanotube is formed,

wherein the linker is NH 3 + ,

(CH 2 ) 3 CO or (CH 3 ) n CH 3 where n is an integer of 0, 1, 2, or 3.

12. A method of forming a nanotube comprising placing in an aqueous media compounds having the formula

wherein X is CH or nitrogen; n is an integer of 0, 1, 2, 3, or 4; Y is absent; and R 1 is C1 to C10 alkyl, straight or branched chain, saturated or unsaturated; and salts thereof.

13. A method of making an implant comprising coating an implant with a nanotube formed from compounds having the formula

wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and salt thereof,

wherein the linker is NH 3 + ,

(CH 2 ) 3 CO or (CH 3 ) n CH 3 where n is an integer of 0, 1, 2, or 3.

14. A method of making an implant comprising coating an implant with a nanotube formed from compounds having the formula

wherein X is CH or nitrogen; n is an integer of 0, 1, 2, 3, or 4; Y is absent; and R 1 is C1 to C10 alkyl, straight or branched chain, saturated or unsaturated; and salts thereof.

15. A method of making an implant comprising coating an implant with a nanotube formed from one or more compounds having the formula

wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and salt thereof,

and one or more compounds having the formula

wherein X is CH or nitrogen; n is an integer of 0, 1, 2, 3, or 4; Y is absent; and R 1 is C1 to C10 alkyl, straight or branched chain, saturated or unsaturated; and salts thereof.

16. A method of promoting growth of tissue at the site of an implant comprising implanting an implant having a coating of nanotubes formed from compounds having the formula

having G^C motifs wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and salt thereof, wherein growth of tissue is promoted by the G^C motifs,

wherein the linker is NH 3 + ,

(CH 2 ) 3 CO or (CH 3 ) n CH 3 where n is an integer of 0, 1, 2, or 3.

17. A method of promoting growth of tissue at the site of an implant comprising implanting an implant having a coating of nanotubes formed from compounds having the formula

wherein X is CH or nitrogen; n is an integer of 0, 1, 2, 3, or 4; Y is absent; and R 1 is C1 to C10 alkyl, straight or branched chain, saturated or unsaturated; and salts thereof.

18. A method of promoting growth of tissue at the site of an implant comprising implanting an implant having a coating of nanotubes formed from compounds having the formula

having G^C motifs wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic, and salt thereof,

and one or more compounds having the formula

wherein X is CH or nitrogen; n is an integer of 0, 1, 2, 3, or 4; Y is absent; and R 1 is C1 to C10 alkyl, straight or branched chain, saturated or unsaturated; and salts thereof,

wherein growth of tissue is promoted by the G^C motifs.

19. A composition comprising nanotubes, a compound for providing mechanical strength and a matrix material, wherein the nanotubes are formed from one or more compounds having Formula II

wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic,

wherein the linker is NH 3 + ,

(CH 2 ) 3 CO or (CH 3 ) n CH 3 where n is an integer of 0, 1, 2, or 3

or one or more compounds having Formula I

wherein X is CH or nitrogen; Y is absent; R 2 is absent or a linker and R 1 is aliphatic.

20. The composition of claim 19 wherein R 2 of Formula I is NH 3 + ,

(CH 2 ) 3 CO or (CH 3 ) n CH 3 where n is an integer of 0, 1, 2, or 3.

21. The composition of claim 19 where R 1 is C 1 to C 10 alkyl, straight or branched chain, saturated or unsaturated.

22. The composition of claim 19 wherein the compound for providing mechanical strength is a nanoparticle of calcium phosphate, hydroxyapatite, apatite, oxyapatite, octacalcium phosphate, monocalcium phosphate, dicalcium phosphate, tricalcium phosphate, β-tricalcium phosphate, α-tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate or calcium dihydrogen phosphate.

23. The composition of claim 19 wherein the matrix material is one or more of polylactic acid, polylactide-coglycolide, polyglycolic acid, polymethylmethacrylate, polyurethane, polycaprolactone, polyethylene, polystyrene, polypropylene, polypyrrole, or poly(2-hydroxyethyl methacrylate).

24. The composition of claim 19 wherein Formula I is absent, X is N, R 1 is methyl, R 2 is (CH 2 ) 3 CO, the compound for providing mechanical strength is a nanoparticle of hydroxyapatite, and the matrix material is poly(2-hydroxyethylmethacrylate).

25. The method of claim 1 wherein the implant is an injectable liquid, moldable putty or hardened structure.

26. The composition of claim 19 wherein the composition is an injectable liquid, moldable putty or hardened structure.

27. The method of claim 1 wherein the implant is a porous hardened structure.

28. The method of claim 1 wherein the implant is a nonporous hardened structure.

29. The composition of claim 19 the composition is in the form of a porous hardened structure.

30. The composition of claim 19 the composition is in the form of a nonporous hardened structure.

31. The method of claim 1 wherein the implant is a plate, rod, screw, cage, scaffold or film.

32. The composition of claim 19 wherein the composition is in the form of a plate, rod, screw, cage, scaffold, film or coating.

33. The method of claim 16 wherein the site of the implant is bone, cartilage, vascular tissue, heart tissue, cardiovascular tissue, bladder tissue, nervous system tissue, skin tissue, spine, a periodontal defect, a dental extraction socket, a cystic defect, a sinus, an alveolar ridge, an oral site, a maxillofacial site or an orthopedic site.

34. The method of claim 17 wherein the site of the implant is bone, cartilage, vascular tissue, heart tissue, cardiovascular tissue, bladder tissue, nervous system tissue, skin tissue, spine, a periodontal defect, a dental extraction socket, a cystic defect, a sinus, an alveolar ridge, an oral site, a maxillofacial site or an orthopedic site.

35. The method of claim 18 wherein the site of the implant is bone, cartilage, vascular tissue, heart tissue, cardiovascular tissue, bladder tissue, nervous system tissue, skin tissue, spine, a periodontal defect, a dental extraction socket, a cystic defect, a sinus, an alveolar ridge, an oral site, a maxillofacial site or an orthopedic site.

36. The method of claim 1 wherein the matrix material is a curable matrix material.

37. The composition of claim 19 wherein the matrix material is a curable matrix material.

38. The method of claim 16 wherein the growth of tissue comprises expansion and growth of cells into tissue wherein the cells are osteoblasts, fibroblasts, endothelial cells, keratinocytes, cardiac myocytes, chondrocytes, synoviocytes, mesenchymel stem cells, neural stem cells, islet cells, hepatocytes, smooth muscle cells, urothelial cells, neurons or Schwann cells.

39. The method of claim 17 wherein the growth of tissue comprises expansion and growth of cells into tissue wherein the cells are osteoblasts, fibroblasts, endothelial cells, keratinocytes, cardiac myocytes, chondrocytes, synoviocytes, mesenchymel stem cells, neural stem cells, islet cells, hepatocytes, smooth muscle cells, urothelial cells, neurons or Schwann cells.

40. The method of claim 18 wherein the growth of tissue comprises expansion and growth of cells into tissue wherein the cells are osteoblasts, fibroblasts, endothelial cells, keratinocytes, cardiac myocytes, chondrocytes, synoviocytes, mesenchymel stem cells, neural stem cells, islet cells, hepatocytes, smooth muscle cells, urothelial cells, neurons or Schwann cells.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2015
From: WEBSTER, THOMAS J.
To: BROWN UNIVERSITY
Reel/Frame 035457/0528 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2015
From: FENNIRI, HICHAM
To: NATIONAL RESEARCH COUNCIL OF CANADA
Reel/Frame 035457/0641 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 21, 2015
From: HEMRAZ, USHA DEVI
To: THE GOVERNORS OF THE UNIVERSITY OF ALBERTA
Reel/Frame 035457/0736 →
CONFIRMATORY LICENSE Recorded Jan 27, 2015
From: BROWN UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 034817/0792 →
Continuity (3)
Continuation 13634340
Provisional Application 61314243 · Mar 16, 2010
Related Publication 20140302109A1 · Oct 9, 2014