Claims
- 1. A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising a mixture of osteoinductive bone material in a carrier forming a composition, the bone material ranging from about 20% to about 65% of the weight of the composition and the carrier comprising a gelatin component dissolved in an aqueous solution, said composition being lyophilized to achieve a cross linking of the gelatin to obtain a structural stability which is maintained after application to said bone site.
- 2. A sterile bone repair composition as claimed in claim 1 wherein said mixture includes bone morphogenic protein in excess of the amount naturally occurring in allogeneic bone.
- 3. A sterile bone repair composition as claimed in claim 1 wherein said osteoinductive bone material is demineralized and said gelatin component ranges from about 10% to about 50% by weight of the composition after lyophilization.
- 4. A sterile bone repair composition as claimed in claim 1 wherein said osteoinductive bone material is demineralized with a calcium content below about 1%.
- 5. A malleable bone composition as claimed in claim 1 wherein said gelatin carrier includes a phosphate buffered saline with a pH ranging from 7.0 to about 7.4.
- 6. A malleable bone composition as claimed in claim I wherein said bone material is partially mineralized with a calcium content between about 4% to about 8%.
- 7. A sterile bone repair composition as claimed in claim 1 wherein said aqueous solution comprises at least one of a group consisting of water, saline and phosphate buffered saline.
- 8. A sterile bone repair composition as claimed in claim 1 wherein said aqueous solution includes a hydrogel of less than 10% by weight.
- 9. A sterile bone repair composition as claimed in claim 8 wherein said hydrogel comprises at least one of a group consisting of sodiumhyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
- 10. A sterile bone repair composition as claimed in claim 1 wherein said aqueous solution has a pH ranging from about 7.0 to about 7.4.
- 11. A sterile bone repair composition as claimed in claim 1 wherein said bone material includes bone particles ranging from 100 mm to 850 mm in size.
- 12. A sterile bone repair composition as claimed in claim 1 wherein said bone material contains growth factors such as transforming growth factor (TGF-beta), platelet derived growth factor (PDGF), osteopontin, fibroblast growth factor (FGF) and insulin-like growth factor (IGF-1).
- 13. A sterile bone repair composition as claimed in claim 1 wherein said carrier also includes a hydrogel ranging from about 1% to about 10% by weight.
- 14. A malleable bone composition as claimed in claim 1 wherein said phosphate includes at least two phosphate ions HPO4−2 and H2PO4−1.
- 15. A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising a mixture of osteoinductive bone material in an aqueous gelatin carrier which is lyophilized to remove the water content leaving a cross linked gelatin bone structure having a structural stability which is maintained after application to said bone repair site with bone material ranging from about 30% to about 60% of the weight of the composition and a gelatin component ranging from about 30% to about 60% by weight of the composition.
- 16. A sterile bone repair composition as claimed in claim 15 wherein said gelatin carrier includes a phosphate buffered saline with a pH ranging from 7.0 to about 7.4.
- 17. A sterile bone repair composition as claimed in claim 16 wherein said phosphate includes at least two phosphate ions HPO4−2 and H2PO4−1.
- 18. A sterile bone repair composition as claimed in claim 15 wherein said gelatin carrier includes a sodium hyaluronate and its derivatives component ranging from about 5% to about 15%.
- 19. A sterile bone repair composition as claimed in claim 15 wherein said bone powder is partially demineralized and has a residual calcium content ranging from about 4% to about 8%.
- 20. A sterile bone repair composition as claimed in claim 15 wherein said aqueous gelating carrier includes a hydrogel comprising at least one of a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
- 21. A sterile bone repair composition as claimed in claim 15 including antimicrobial and/or antibiotics such as erythromycin, bacitracin, neomycin, penicillin, polymyxin B, tetracycline, viomycin, chloromycetin and streptomycin, cefazolin, ampicillin, azactam, tobramycin, clindamycin, gentamycin and vitamins.
- 22. A sterile bone repair composition as claimed in claim 15 wherein said composition includes bone morphogenic proteins in excess of the amount naturally occurring in allogeneic bone.
- 23. A sterile bone repair composition as claimed in claim 15 wherein said composition has a pH ranging from 6.8 to 7.4.
- 24. A sterile bone repair composition as claimed in claim 15 wherein said bone powder contains growth factors such as transforming growth factor (TGF-beta), platelet derived growth factor (PDGF), osteopontin, fibroblast growth factor (FGF) and insulin-like growth factor (IGF-1).
- 25. A sterile bone repair composition as claimed in claim 15 wherein said hydrogel comprises at least one of a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
- 26. A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising a new bone growth inducing partially demineralized lyophilized allograft bone powder with a residual calcium content of about 4 to 8% and a particle size ranging from about 100 to about 850 microns in an aqueous gelatin carrier which is lyophilized to remove water content leaving a cross linked gelatin bone structure having a structural stability which is maintained after application to said bone repair site with bone material ranging from about 30% to about 50% of the weight of the composition and the cross linked gelatin ranging from 30% to 60% by weight of the composition.
- 27. A sterile bone repair composition as claimed in claim 26 wherein said osteoinductive bone material is demineralized with a calcium content below about 1%.
- 28. A sterile bone repair composition as claimed in claim 26 wherein said aqueous gelatin carrier includes phosphate buffered saline.
- 29. A sterile bone repair composition as claimed in claim 26 wherein said aqueous carrier includes a hydrogel of less than 10% by weight.
- 30. A sterile bone repair composition as claimed in claim 29 wherein said hydrogel comprises at least one of a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
- 31. A sterile bone repair composition as claimed in claim 26 wherein said carrier has a pH ranging from about 7.0 to about 7.4.
- 32. A sterile bone repair composition as claimed in claim 25 wherein said bone powder contains growth factors such as transforming growth factor (TGF-beta), platelet derived growth factor (PDGF), osteopontin, fibroblast growth factor (FGF) and insulin-like growth factor (IGF-1).
- 33. A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site comprising a new bone growth inducing partially demineralized lyophilized allograft bone powder, a particle size ranging from about 100 to about 850 microns mixed in an aqueous gelatin carrier having a hydrogel component ranging from 5% to 10% by weight to form a composition which is lyophilized to remove water content leaving a cross linked gelatin bone structure having a structural stability which is maintained after application to said bone defect site with bone material ranging from about 30% to about 50% of the weight of the composition and the cross linked gelatin ranging from 30% to 60% by weight of the composition.
- 34. A sterile bone repair composition as claimed in claim 33 wherein said aqueous gelatin carrier includes a phosphate buffered saline.
- 35. A sterile bone repair composition as claimed in claim 34 wherein said phosphate buffered saline has a pH ranging from about 7.1 to about 7.4.
- 36. A sterile bone repair composition as claimed in claim 33 wherein said aqueous carrier includes a hydrogel of less than 10% by weight.
- 37. A sterile bone repair composition as claimed in claim 33 wherein said aqueous gelatin carrier hydrogel comprises at least one of a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
- 38. A sterile bone repair composition as claimed in claim 37 wherein said carrier has a pH ranging from about 7.0 to about 7.4.
- 39. A sterile bone repair composition for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing compound of partially demineralized lyophilized allograft bone material with a calcium content greater than 4% and less than 8% dry weight and a particle size ranging from about 100 to about 850 microns mixed and in an aqueous gelatin carrier having a hydrogel component comprising a glycosaminoglycan ranging from about 5.0% to about 15.0% by weight of the composition and having a molecular weight of at least 700,000 Daltons which is lyophilized to remove water content leaving a cross linked gelatin bone structure having a structural stability which is maintained after application to said bone repair site with bone material ranging from about 30% to about 50% of the weight of the composition and the cross linked gelatin ranging from 30% to 60% by weight of the composition.
- 40. A sterile bone repair composition as claimed in claim 39 wherein said glycosaminoglycan is sodium hyaluronate and its derivatives.
- 41. A sterile bone repair composition as claimed in claim 30 wherein said aqueous gelatin carrier includes a phosphate buffered saline.
- 42. A sterile bone repair composition as claimed in claim 31 wherein said phosphate buffered saline has a pH ranging from about 7.1 to about 7.4.
- 43. An osteoimplant for application to a bone defect site to promote new bone growth at the site comprising new bone growth inducing demineralized bone material with a particle size ranging from about 100 to about 850 microns mixed in an aqueous gelatin carrier with a hydrogel component comprising a glycosaminoglycan ranging from about 5.0% to about 10.0% by weight of the composition, said mixture being lyophilized to remove water content leaving a cross linked gelatin bone structure having a structural stability which is maintained after application to said bone repair site with bone material ranging from about 35% to about 60% of the weight of the composition and the cross linked gelatin ranging from 25% to 45% by weight of the composition.
- 44. An osteoimplant as claimed in claim 43 wherein said aqueous gelatin carrier includes a glycosaminoglycan selected from a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylmethylcellulose (HPMC).
- 45. An osteoimplant for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing compound of partially demineralized lyophilized allograft bone material in a phosphate buffered aqueous gelatin carrier which is lyophilized to remove water content leaving a cross linked gelatin bone structure having a structural stability which is maintained after application to said bone repair site, said bone material ranging from about 30% to about 60% of the weight of the structure and the cross linked gelatin ranging from 30% to 60% by weight of the structure and the water content of said structure ranging from about 0.1% to about 1.0%.
- 46. A method of constructing a cross linked osteoinductive bone repair construct. comprising the steps of:
a. mixing osteoinductive bone material in an aqueous gelatin mixture to obtain a formulation; and b. subjecting said formulation to lyophilization to remove water from said aqueous gelatin mixture cross linking said gelatin and osteoinductive bone material contained therein to form a solid structure.
- 47. A method as claimed in claim 46 wherein said osteoinductive bone material is powdered bone ranging from about 100 microns to about 850 microns.
- 48. A method as claimed in claim 46 wherein said osteoinductive bone material is powdered bone with a residual calcium content ranging from about 4% to about 8%.
- 49. A method as claimed in claim 46 wherein said osteoinductive bone material is powdered bone which has been demineralized to have a residual calcium content which is less than 1%.
- 50. A method as claimed in claim 46 wherein said osteoinductive bone material includes mineralized bone chips.
- 51. A method of constructing a cross linked osteoinductive bone repair construct comprising the steps of:
a. dissolving a gelatin in an aqueous solution; b. mixing osteoinductive bone material in an aqueous gelatin mixture to obtain a formulation; c. shaping said formulation into a specific shape; and d. subjecting said formulation to lyophilization to remove at least 90% of water from said aqueous gelatin osteoinductive bone mixture cross linking said gelatin and osteoinductive bone material contained therein to form a solid structure.
- 52. A method as claimed in claim 51 wherein said aqueous solution comprises at least one of a group consisting of phosphate buffered saline, saline and water.
- 53. A method as claimed in claim 51 wherein said aqueous solution includes a hydrogel of less than 10% by weight.
- 54. A method as claimed in claim 51 wherein said hydrogel comprises at least one of a group consisting of sodium hyaluronate and its derivatives, chitosan, sodium alginate, dextran, carboxymethylcellulose (CMC) and hydroxypropylnethylcellulose (HPMC).
- 55. A method as claimed in claim 51 wherein said aqueous solution has a pH ranging from about 7.0 to about 7.4.
- 56. A method of constructing a cross linked osteoinductive bone repair construct comprising the steps of:
a. dissolving a gelatin in an aqueous solution; b. mixing from 20% to 50% by weight osteoinductive bone material in an aqueous gelatin mixture to obtain a bone repair formulation; c. shaping said bone repair formulation into a specific shape; and d. lyophilizing said bone repair formulation for a period of time sufficient to leave from 0.01 to 0.8% water in said aqueous gelatin osteoinductive bone formulation and cross link said gelatin with said osteoinductive bone material contained therein to form a solid structure.
- 57. A method as claimed in claim 56 wherein said aqueous solution comprises at least one of a group consisting of phosphate buffered saline, saline and water.
- 58. A method as claimed in claim 56 wherein said aqueous solution includes the addition of a hydrogel of less than 10% by weight of said formulation.
- 59. A method as claimed in claim 56 wherein said lyophilization is at −40° C. for about 4 hours.
- 60. A method as claimed in claim 56 wherein said aqueous solution includes a hydrogel of less than 10% by weight.
- 61. A method of constructing a cross linked osteoinductive bone repair construct comprising the steps of:
a. dissolving a gelatin in an aqueous solution containing a glycosaminoglycan; b. mixing osteoinductive demineralized bone material having a size ranging from 100 microns to 2 mm in said aqueous gelatin mixture to obtain a formulation; c. shaping said formulation into a specific shape; and d. subjecting said formulation to lyophilization to remove at least 90% of water from said aqueous gelatin osteoinductive bone mixture cross linking said gelatin and osteoinductive demineralized bone material contained therein to form a solid structure.
- 62. A method as claimed in claim 61 wherein said lyophilization of step d. is conducted for at least 4 hours at which the temperature is raised thereafter to about +35° C. for 20 to 28 hours with the formulation at the higher temperature being placed under a vacuum of about 350 mTorr.
- 63. A method as claimed in claim 61 wherein about 0.1 to about 8% of the original water is left in the formulization after lyophilization.
RELATED APPLICATIONS
[0001] This is a continuation-in-part of U.S. patent application Ser. No. 09/983,526, filed Oct. 24, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09/515,656, filed Feb. 29, 2001 which is a continuation-in-part of U.S. patent application Ser. No. 09/031,750, filed Feb. 27, 1998 and issued into U.S. Pat. No. 6,030,635 on Feb. 29, 2000, the “656 Application also being a continuation-in-part of U.S. patent application Ser. No. 09/365,880, filed Aug. 3, 1999, which is a continuation application of U.S. patent application Ser. No. 09/031,750 which has issued into U.S. Pat. No. 6,030,635.
Continuations (1)
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Number |
Date |
Country |
Parent |
09031750 |
Feb 1998 |
US |
Child |
09365880 |
Aug 1999 |
US |
Continuation in Parts (4)
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Number |
Date |
Country |
Parent |
09983526 |
Oct 2001 |
US |
Child |
10150097 |
May 2002 |
US |
Parent |
09515656 |
Feb 2000 |
US |
Child |
09983526 |
Oct 2001 |
US |
Parent |
09031750 |
Feb 1998 |
US |
Child |
09515656 |
Feb 2000 |
US |
Parent |
09365880 |
Aug 1999 |
US |
Child |
09515656 |
Feb 2000 |
US |