Injectable hydrogels and methods of making and using same

• US 20060257488A1
• Filed: 05/10/2006
• Published: 11/16/2006
• Est. Priority Date: 05/10/2005
• Status: Abandoned Application

• Current Assignee: Cytophil Incroporated
• Original Assignee: Cytophil Incroporated
• Inventors: Hubbard, William G.
• Application Number:
  US11/431,276
• Publication Number:
  US 20060257488A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A biocompatible hydrogel and method for augmenting soft and hard tissue, wherein the hydrogel comprises at least one gel former and the hydrogel is used to augment tissue when introduced into a desired tissue site. The hydrogel may comprise at least one of a carbomer, a poloxamer and a combination thereof. The hydrogel may have a yield strength of about 300 gm/cm-sec to about 12,000 gm/cm-sec and require less than about 10 lbf to extrude the hydrogel from a 1 cc syringe having a 25 gauge ½″ length needle at a rate of 2 inches per minute.

Claims

1. A biocompatible hydrogel for augmenting tissue, the hydrogel comprising at least one of a carbomer, a poloxamer and a combination thereof, the hydrogel augmenting tissue when introduced into a desired tissue site.

2. The hydrogel of claim 1, wherein the composition comprises a carbomer.

3. The hydrogel of claim 1, wherein the composition comprises a poloxamer.

4. The hydrogel of claim 1, further comprising particles suspended therein.

5. The hydrogel of claim 4, wherein the particles have a size ranging from about 15 microns to about 1000 microns.

6. The hydrogel of claim 4, wherein the particles comprise at least one of calcium phosphate, calcium hydroxylapatite, alpha tricalcium phosphate, beta tricalcium phosphate, calcium pyrophosphate, tetracalcium phosphate, octacalcium phosphate, calcium carbonate, fluorapatite, alumina, zirconia, carbon, polymethylmethacrylate, polyglycolic acid, polylactic acid, ceramic, glass, metal, polymers, and a combination thereof.

7. The hydrogel of claim 4, wherein the particles comprise calcium hydroxylapatite.

8. The hydrogel of claim 1, further comprising at least one drug.

9. The hydrogel of claim 8, wherein the drug comprises at least one of lidocaine, epinephrine and a combination thereof.

10. The hydrogel of claim 1, further comprising at least one growth factor.

11. The hydrogel of claim 10, wherein the growth factor comprises at least one of P15 human growth hormone, β

FDGF and a combination thereof.

12. The hydrogel of claim 1, further comprising at least one of a hypotonic solution, a hypertonic solution and an isotonic solution.

13. The hydrogel of claim 1, further comprising at least one of glycerin, polyethylene glycol, propylene glycol, a surfactant and a combination thereof.

14. The hydrogel of claim 1, further comprising at least one additional gel former.

15. The hydrogel of claim 1, wherein the composition comprises both a carbomer and a poloxamer.

16. The hydrogel of claim 1, wherein the hydrogel has a yield strength of about 300 gm/cm-sec to about 12,000 gm/cm-sec and requires less than 10 lbf to extrude the hydrogel from a 1 cc syringe having a 25 gauge ½

″

length needle at a rate of 2 inches per minute.

17. The hydrogel of claim 1, wherein the hydrogel is encapsulated by an elastomeric shell.

18. A kit comprising a syringe filled with the hydrogel of claim 1.

19. The hydrogel of claim 1, further comprising a particulate ceramic material homogeneously suspended in the gel prior to and during introduction of the biocompatible composition to the desired site.

20. The hydrogel of claim 1, wherein the hydrogel has a thermal transition temperature in the range of about 15°

C. to about 37°

C.

21. The hydrogel of claim 1, wherein increasing the pH of the hydrogel by about 1 pH unit more than triples the yield strength of the hydrogel.

22. A hydrogel comprising at least one gel former, wherein the hydrogel has a yield strength of about 300 gm/cm-sec to about 12,000 gm/cm-sec and requires less than about 10 lbf to extrude the hydrogel from a 1 cc syringe having a 25 gauge ½

″

length needle at a rate of 2 inches per minute.

23. The hydrogel of claim 22, wherein the yield strength is about 1,500 gm/cm-sec to about 7,500 gm/cm-sec.

24. The hydrogel of claim 22, wherein the hydrogel requires less than about 8 lbf to extrude the hydrogel from a 1 cc syringe having a 25 gauge ½

″

length needle at a rate of 2 inches per minute.

25. The hydrogel of claim 22, further comprising particles comprising at least one of calcium phosphate, calcium hydroxylapatite, alpha tricalcium phosphate, beta tricalcium phosphate, calcium pyrophosphate, tetracalcium phosphate, octacalcium phosphate, calcium carbonate, fluorapatite, alumina, zirconia, carbon, polymethylmethacrylate, polyglycolic acid, polylactic acid, ceramic, glass, metal, polymers, and a combination thereof.

26. The hydrogel of claim 25, wherein the particles within the hydrogel undergo less than about 5 mm of separation when a 2.5 gram sample of the hydrogel is centrifuged at 500 g'"'"'s for 5 minutes.

27. The hydrogel of claim 25, wherein the particles within the hydrogel undergo less than about 3 mm separation when a 2.5 gram sample of the hydrogel is centrifuged at 500 g'"'"'s for 5 minutes.

28. The hydrogel of claim 22, further comprising at least one of lidocaine, epinephrine and a combination thereof.

29. The hydrogel of claim 22, further comprising at least one growth factor.

30. The hydrogel of claim 22, further comprising at least one of a hypotonic solution, a hypertonic solution and an isotonic solution.

31. A method for augmenting soft or hard tissue, the method comprising introducing at a desired soft or hard tissue site a hydrogel comprising at least one of a carbomer, a poloxamer and a combination thereof to augment the soft or hard tissue site.

32. The method of claim 31, wherein the hydrogel is introduced to the desired site by at least one of injection and implantation.

33. The method of claim 31, further comprising placing the hydrogel in an elastomeric shell prior to introducing the hydrogel to the desired site.

34. The method of claim 31, wherein the hydrogel further comprises particles suspended therein.

35. The method of claim 34, wherein the particles have a size ranging from about 15 microns to about 1000 microns.

36. The method of claim 34, wherein the particles comprise at least one of calcium phosphate, calcium hydroxylapatite, alpha tricalcium phosphate, beta tricalcium phosphate, calcium pyrophosphate, tetracalcium phosphate, octacalcium phosphate, calcium carbonate, fluorapatite, alumina, zirconia, carbon, polymethylmethacrylate, polyglycolic acid, polylactic acid, ceramic, glass, metal, polymers, and a combination thereof.

37. The method of claim 34, wherein the particles comprise calcium hydroxylapatite.

38. The method of claim 31, wherein the hydrogel further comprises at least one drug.

39. The method of claim 38, wherein the drug comprises at least one of lidocaine, epinephrine and a combination thereof.

40. The method of claim 31, wherein the hydrogel further comprises at least one growth factor.

41. The method of claim 40, wherein the growth factor comprises at least one of P15 human growth hormone, β

FDGF and a combination thereof.

42. The method of claim 31, wherein the hydrogel further comprises at least one of a hypotonic solution, a hypertonic solution and an isotonic solution.

43. The method of claim 31, wherein the hydrogel further comprises at least one of glycerin, polyethylene glycol, propylene glycol a surfactant and a combination thereof.

44. The method of claim 31, wherein the hydrogel further comprises at least one additional gel former.

45. The method of claim 31, wherein the hydrogel has a yield strength of about 300 gm/cm-sec to about 12,000 gm/cm-sec and requires less than about 10 lbf to extrude the hydrogel from a 1 cc syringe having a 25 gauge ½

″

length needle at a rate of 2 inches per minute.

46. The method of claim 31, wherein the hydrogel is encapsulated by an elastomeric shell.

47. The method of claim 31, wherein the hydrogel further comprises a particulate ceramic material homogeneously suspended in the gel prior to and during introduction of the biocompatible composition to the desired site.

48. The method of claim 31, wherein the hydrogel has a thermal transition temperature in the range of about 15°

C. to about 37°

C.

49. The method of claim 31, wherein increasing the pH of the hydrogel by about 1 pH unit more than triples the yield strength of the hydrogel.

50. A method for augmenting soft or hard tissue, the method comprising introducing a particle dry-coated with at least one gel former into a desired soft or hard tissue site.