Malleable paste with allograft bone reinforcement for filling bone defects

• US 6,458,375 B1
• Filed: 10/03/2000
• Issued: 10/01/2002
• Est. Priority Date: 02/27/1998
• Status: Expired due to Term

• Current Assignee: Musculoskeletal Transplant Foundation
• Original Assignee: Musculoskeletal Transplant Foundation
• Inventors: Sunwoo, Moon Hae, Gertzman, Arthur A.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): DI NOLA BARON, LILIANA
• Application Number:
  US09/677,891
• Time in Patent Office: 728 Days
• Field of Search: 623/23.61, 623/23.62, 623/23.63, 424/422, 424/423, 424/488, 424/400
• US Class Current: 424/423
• CPC Class Codes: A61B 17/86 Pins or screws or threaded wires; nuts therefor A61B17/72 take precedence
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2/446 having a circular or elliptical cross-section substantially parallel to the axis of the spine, e.g. cylinders or frustocones
• CPC Class Codes: A61F 2/447 substantially parallelepipedal, e.g. having a rectangular or trapezoidal cross-section
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/2839 Bone plugs or bone graft dowels
• CPC Class Codes: A61F 2002/30059 differing in bone mineralization, e.g. made from both mineralized and demineralized adjacent parts
• CPC Class Codes: A61F 2002/302 toroidal, e.g. rings
• CPC Class Codes: A61F 2002/30224 cylindrical
• CPC Class Codes: A61F 2002/3023 wedge-shaped cylinders
• CPC Class Codes: A61F 2002/30261 parallelepipedal
• CPC Class Codes: A61F 2002/30843 Pyramidally-shaped
• CPC Class Codes: A61F 2002/30892 parallel
• CPC Class Codes: A61F 2002/30894 inclined obliquely with respect to each other
• CPC Class Codes: A61F 2230/0065 toroidal, e.g. ring-shaped, doughnut-shaped
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61F 2230/0082 parallelepipedal
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/32 : Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 38/1875 : Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61L 24/0005 : Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: A61L 24/0031 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/0094 : containing macromolecular fillers
• CPC Class Codes: A61L 2430/02 : for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/3608 : Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/365 : Bones
• CPC Class Codes: A61L 27/3847 : Bones
• CPC Class Codes: A61L 27/48 : with macromolecular fillers
• CPC Class Codes: A61L 27/52 : Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/005 : Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

The invention is directed toward a sterile malleable bone composition for application to a bone defect site to promote new bone growth at the site comprising a mixture of demineralized osteogenic bone powder with a particle size ranging from about 250 to about 750 microns and surface demineralized cortical bone rods having a diameter ranging from 1.0 mm to 5.00 mm or larger bone chips. The surface demineralized cortical bone rods have diameter to length ratio ranging from 1:2 to 1:20. The demineralized bone powder range from about 25 to about 30% of the weight of the composition and the cortical bone rods range from 5% to about 10% of the weight of the composition with the carrier being selected from the high molecular weight hydrogel in aqueous solution having a high molecular weight over 700,000 Daltons and ranging from about 2.0% to about 5.0% by weight of the carrier solution.

Claims

1. A sterile malleable bone composition for application to a bone defect site to promote new bone growth at the site comprising a mixture of demineralized osteogenic or osteoconductive bone powder with a particle size ranging from about 250 to about 750 microns and osteogenic bone chips of a larger size ranging from 0.1 to 10 mm in a carrier, the demineralized bone powder ranging from about 15% to about 35% of the weight of the composition and the osteogenic bone chips ranging from 5% to about 20% of the weight of the composition, the carrier being selected from a aqueous sodium based phosphate buffered solution and a hydrogel consisting of a mucopolysaccharide, said mucopolysaccharide having a high molecular weight ranging from seven hundred thousand to three million Daltons and ranging from about 2.0% to about 5.0% by weight of the carrier solution, said composition having a pH ranging from about 7.2 to about 7.4.

2. A sterile malleable bone composition as claimed in claim 1 wherein said composition includes added bone morphogenic proteins.

3. A sterile malleable bone composition as claimed in claim 1 wherein said phosphate includes two phosphate ions HPO₄⁻

2 and H₂PO₄<sup>−

1</sup>.

4. A sterile malleable bone composition as claimed in claim 1 wherein said composition has an isotonic state of about 300 mOsmol/Kg.

5. A sterile malleable bone composition as claimed in claim 1 comprising the addition of a calcium salt to the carrier.

6. A sterile malleable bone composition as claimed in claim 1 wherein the balance of the carrier formulation contains a sodium phosphate buffer and has a pH of about 7.2.

7. A sterile malleable bone composition as claimed in claim 1 wherein said bone powder is cortical allograft bone powder.

8. A sterile malleable bone composition as claimed in claim 1 wherein said bone powder is cortical-cancellous allograft bone powder.

9. A sterile malleable bone composition as claimed in claim 1 wherein said bone chips are cortical allograft bone chips.

10. A sterile malleable bone composition as claimed in claim 1 wherein said bone chips are cortical-cancellous allograft bone chips.

11. A sterile malleable bone composition as claimed in claim 1 wherein said bone chips are mineralized allograft bone chips.

12. A sterile malleable bone composition as claimed in claim 1 wherein said bone chips are demineralized allograft bone chips.

13. A sterile malleable bone composition as claimed in claim 1 wherein antimicrobial and/or antibiotics selected from the group consisting essentially of erythromycin, bacitracin, neomycin, penicillin, polymyxin B, tetracycline, viomycin, chloromycetin and streptomycin, cefazolin, ampicillin, azactam, tobramycin, clindamycin and gentamycin are added to said composition.

14. A sterile malleable bone composition as claimed in claim 1 wherein said hydrogel is sodium hyaluronate.

15. A sterile malleable bone composition as claimed in claim 1 wherein said hydrogel is chitosan.

16. A sterile malleable bone composition as claimed in claim 1 wherein said composition has a pH ranging from 6.8 to 7.4.

17. A sterile malleable bone composition as claimed in claim 1 wherein the aqueous solution includes an ionic salt based phosphate buffer.

18. A sterile malleable bone composition as claimed in claim 1 wherein said hydrogel has a molecular weight of at least 700,000 Daltons.

19. A sterile malleable bone composition as claimed in claim 1 wherein said hydrogel has a molecular weight of at least of 1,000,000 Daltons.

20. A sterile malleable bone composition as claimed in claim 1 wherein said hydrogel consists of the group of sodium hyaluronate and chitosan.

21. A sterile malleable bone composition as claimed in claim 1 wherein said hydrogel substantially maintains its viscosity from 22-37 degrees C.

22. A sterile malleable bone composition as claimed in claim 1 wherein said aqueous solution is saline.

23. A sterile malleable bone composition for application to a bone defect site to promote new bone growth at the site comprising a carrier and a mixture of demineralized osteogenic bone powder with a particle size ranging from about 250 to about 1000 microns and cortical bone rods having a length ranging from 1 mm to about 10 mm and a thickness to length ratio ranging of about 1:

2 to 1;

20, the demineralized bone powder ranging from about 15 to about 30% of the weight of the composition and the cortical bone rods ranging from 5% to about 20% of the weight of the composition, said carrier comprising a hydrogel selected from a group consisting of sodium hyaluronate, chitosan and carboxy-methyl-cellulose in saline phosphate buffer solution, said hydrogel having a high molecular weight ranging from about seven hundred thousand to about three million Daltons and ranging from about 2.0% to about 5.0% by weight of the carrier solution, said composition having a substantially neutral osmolality.

24. A sterile malleable bone composition as claimed in claim 23 wherein said composition mixture includes added bone morphogenic proteins.

25. A sterile malleable bone composition as claimed in claim 23 wherein said phosphate buffer includes two phosphate ions HPO₄⁻

2 and H₂PO₄<sup>−

1</sup>.

26. A sterile malleable bone composition as claimed in claim 23 wherein said composition has an isotonic state of about 300 mOsmol/Kg.

27. A sterile malleable bone composition as claimed in claim 23 wherein said bone rods are orientated in one direction in said composition.

28. A sterile malleable bone composition as claimed in claim 23 wherein antimicrobial and/or antibiotics selected from the group consisting essentially of erythromycin, bacitracin, neomycin, penicillin, polymyxin B, tetracycline, viomycin, chloromycetin and streptomycin, cefazolin, ampicillin, azactam, tobramycin, clindamycin and gentamycin are added to said composition.

29. A sterile malleable bone composition as claimed in claim 23 wherein said hydrogel has a molecular weight of at least one million Daltons.

30. A sterile malleable bone composition as claimed in claim 23 wherein said bone rods have a diameter ranging from 0.4 mm to about 2.0 mm.

31. A sterile malleable bone composition as claimed in claim 23 wherein said cortical bone rods are partially demineralized.

32. A sterile malleable bone composition as claimed in claim 31 wherein said bone rods have a diameter ranging from 3.0 mm to about 5.00 mm.

33. A sterile malleable bone composition as claimed in claim 23 wherein said cortical bone rods are fully demineralized and flexible.

34. A sterile malleable bone composition as claimed in claim 23 wherein said cortical bone rods are randomly orientated in said composition.

35. A sterile malleable bone composition for application to a bone defect site to promote new bone growth at the site comprising a carrier and a mixture of demineralized osteogenic bone powder with a particle size ranging from about 250 to about 750 microns and surface demineralized cortical bone rods having a diameter ranging from 1.0 mm to 5.00 mm with a diameter to length ratio ranging from 1:

2 to 1;

20, the demineralized bone powder ranging from about 25 to about 30% of the weight of the composition and the cortical bone rods ranging from 5% to about 10% of the weight of the composition, said carrier comprising a high molecular weight hydrogel mucosaccharide in aqueous phosphate buffered solution, said mucosaccharide having a high molecular weight over 700,000 Daltons and ranging from about 2.0% to about 5.0% by weight of the carrier solution.

36. A sterile malleable bone composition as claimed in claim 35 wherein said cortical bone rods are randomly oriented in said composition.

37. A sterile malleable bone composition as claimed in claim 35 wherein said cortical bone rods are oriented in one direction in said composition.

38. A sterile malleable bone composition for application to a bone defect site to promote new bone growth at the site comprising a carrier and a mixture of demineralized osteogenic bone powder with a particle size ranging from about 250 to about 1000 microns and mineral cortical bone rods having a diameter ranging from 0.4 to about 2.0 mm and a diameter to length ratio of about 2- to about 6, the demineralized bone powder ranging from about 25 to about 35% of the weight of the composition and the mineralized cortical rods ranging from 5% to about 25% of the weight of the composition, said carrier comprising a hydrogel selected from a group consisting of sodium hyaluronate, chitosan and carboxy-methyl-cellulose in a buffered phosphate saline solution, said hydrogel having a high molecular weight of at least 1.0-10⁶ Daltons and ranging from about 1.0% to about 5.0% by weight of the carrier solution.

39. A sterile malleable bone putty composition for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing mixture of demineralized lyophilized allograft bone powder with a particle size ranging from about 250 to about 750 microns and mineralized cortical allograft bone chips ranging from 1.0 mm to 10.00 mm in size and cortical bone rods in a hyaluronic acid saline phosphate buffer carrier, the hyaluronic acid component ranging from above 2.0% to about 5% of the carrier solution and having a molecular weight of at least 1.0×

10⁶ Daltons, the total bone content of the bone powder, bone chips and bone rods in the carrier ranging in weight from about 30% to about 50% total weight of the composition.

40. A sterile malleable bone putty composition for application to a bone defect site to promote new bone growth at the site comprising a new bone growth inducing demineralized lyophilized allograft bone powder with a particle size ranging from about 250 to about 750 microns and mineralized bone chips ranging from 0.1 mm-10 mm in a high molecular weight sodium hyaluronate and saline carrier with a phosphate buffer, the bone content of the composition ranging from about 25% to about 45% by weight and the high molecular weight sodium hyaluronate component ranges from about 2% to about 5% of the carrier and has a molecular weight greater than one million Daltons.

41. A sterile malleable bone putty composition for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing demineralized lyophilized allograft bone powder with a particle size ranging from about 250 to about 750 microns and mineralized bone chips ranging from 1-10 mm in size in a carrier solution, said carrier solution comprising a high molecular weight chitosan having a molecular weight over 1.0×

10⁵ Daltons in an aqueous buffered phosphate with the bone content of the putty composition ranging from about 30% to about 35% and the chitosan component ranging from 2 to 5% of the carrier solution and said composition having a substantially neutral osmolality.

42. A sterile malleable bone putty composition for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing demineralized lyophilized allograft bone powder with a particle size ranging from about 250 to about 750 microns and mineralized bone cordical bone rods having a diameter to length ratio ranging from 1:

2-1;

20 mm in length in a carrier, said carrier comprising a high molecular weight chitosan having a molecular weight over 1.0×

10⁶ Daltons in a water phosphate buffered solution with the bone content of the putty composition ranging from about 30% to about 35% and the chitosan component ranging from 2 to 5% of the carrier solution and said composition having a substantially neutral osmolality.

43. A sterile malleable bone putty as claimed in claim 42 wherein said cortical bone rods are mineralized.

44. A sterile malleable bone putty as claimed in claim 42 wherein said cortical bone rods are partially demineralized.

45. A sterile malleable bone putty as claimed in claim 42 wherein said cortical bone rods are fully demineralized.

46. A sterile malleable bone putty composition for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing demineralized lyophilized allograft bone powder with a particle size ranging from about 250 to about 750 microns and mineralized bone cordical bone rods having a diameter to length ratio ranging from 1:

2-1;

20 mm in length in a high molecular weight carboxy-methyl-cellulose phosphate buffered water carrier solution with the bone content of the putty composition ranging up to 30% and the carboxy-methyl-cellulose component ranging from 2 to 5% by weight of the carrier solution.

47. A sterile malleable bone putty as claimed in claim 46 wherein said cortical bone rods are mineralized.

48. A sterile malleable bone putty as claimed in claim 46 wherein said cortical bone rods are partially demineralized.

49. A sterile malleable bone putty as claimed in claim 46 wherein said cortical bone rods are fully demineralized.