Pore-forming agents for orthopedic cements 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
CA2460843 A1 2003-03-27 [CA2460843] / 2003-03-27
申请号/申请日
2002CA-2460843 / 2002-09-20
发明人
KULKARNI SHAILESH C;TOTH CAROL ANN;LANDERYOU TRACY J;DALAL PARESH S;
申请人
STRYKER;
主分类号
IPC分类号
A01N-043/04A01N-063/00A61BA61F-002/00A61F-013/00A61L-027/00A61L-027/12A61L-027/22A61L-027/56C07K-014/47C08J-009/26C08J-009/28
摘要
(CA2460843) A bone precursor composition comprising a cement mixture and a pore-forming agent is provided for bone implant.  Preferably, the pore-forming agent has a particle size of 20-500 .mu.m.  More preferably, the proportion of the pore- forming agent is 7-40% (w/w).  The composition may further include a bioactiv e agent, preferably a bone morphogenic protein or nucleic acid encoding BMP encapsulated in the pore-forming agent.  The moldability of the composition c an be modulated by the addition of a binder.  The invention provides a kit and implant device comprising the bone precursor composition.  The invention also provides an implantable prosthetic device comprising a prosthetic implant having a surface region and a bone precursor material disposed on the surfac e region.  The kit and devices may further comprise one or more additional components including a bioactive agent and a binder.  Methods of inducing bon e formation and delivering the bioactive agent are provided.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2001US-09960421 2001-09-21 2002WO-US29966 2002-09-20
主权利要求
(CA2460843)  We claim: 1. A bone precursor composition comprising a cement mixture and a pore-forming agent, wherein the pore-forming agent has a particle size of 20-500 [mu]m;  with the proviso that when the pore-forming agent is PLGA, the particle size is 20-140 [mu]m or 310-500 [mu]m and when the pore forming agent is calcium sulfate, the particle size is 20-140 [mu]m or 260-500 [mu]m. 2. A bone precursor composition comprising a cement mixture and a pore-forming agent, wherein the pore-forming agent has a particle size of 20-140 [mu]m. 3. A bone precursor composition comprising a cement mixture and a pore-forming agent, wherein the pore-forming agent has a particle size of 75-140 [mu]m. 4. A bone precursor composition according to any one of claims 1 to 3, wherein the proportion of poreforming agent is 7-40% (w/w). 5. A bone precursor composition according to any one of claims 1 to 3, wherein the proportion of poreforming agent is 7-25% (w/w). 6. A bone precursor composition according to any one of claims 1 to 3, wherein the proportion of poreforming agent is 7-14% (w/w) and the pore-forming agent is PLGA. 7. The bone precursor composition of any one of claims 1 to 3, wherein the cement mixture comprises a mixture selected from the group consisting of a calcium phosphate cement mixture and a calcium sulfate cement mixture. 8. The bone precursor composition of any one of claims 1 to 3, wherein the cement mixture comprises a mixture selected from the group consisting of: a) a mixture of decarbonated amorphous calcium phosphate and a second calcium phosphate;  b) a mixture of tetracalcium phosphate and a second calcium phosphate;  c) a mixture of monocalcium phosphate, tricalcium phosphate and calcium carbonate;  d) a mixture of beta-tricalcium phosphate and monocalcium phosphate monohydrate, and optionally, comprising calcium pyrophosphate, calcium sulfate dehydrate and calcium sulfate hemihydrate;  e) a mixture of beta-tricalcium phosphate, dicalcium phosphate dehydrate and calcium carbonate;  and f) calcium sulfate hemihydrate. 9. The bone precursor composition of claim 8, wherein the second calcium phosphate is selected from the group consisting of monocalcium phosphate, dicalcium phosphate anhydrous, dicalcium phosphate dehydrate, calcium metaphosphate, heptacalcium phosphate, calcium pyrophosphate, alpha-tricalcium phosphate, beta-tricalcium phosphate, octacalcium phosphate and amorphous calcium phosphate. 10. The bone precursor composition of any one of claims 1 to 3, wherein the pore-forming agent is a natural or synthetic biodegradable polymer. 11. The bone precursor composition of any one of claims 1 to 3, wherein the pore-forming agent is selected from the group consisting of ethylenevinylacetate, natural and synthetic collagen, poly(glaxanone), poly(phosphazenes), polyglactin, polyglactic acid, polyaldonic acid, polyacrylic acids, polyalkanoates, polyorthoesters, poly(L-lactide) (PLLA), poly(D,L-lactide) (PDLLA), polyglycolide (PGA), poly(lactide-co-glycolide (PLGA), poly (-caprolactone), poly(trimethylene carbonate), polyp-dioxanone), poly([zeta]-caprolactone-co-glycolide), poly(glycolide-co-trimethylene carbonate) poly(D,L-lactide-co-trimethylene carbonate), polyarylates, polyhydroxybutyrate (PHB), polyanhydrides, poly(anhydride-co-imide) and co-polymers thereof, polymers of amino acids, propylene-co-fumarates, a polymer of one or more [alpha]-hydroxy carboxylic acid monomers, calcium sulfate, bioactive glass compositions, admixtures thereof and any derivatives and modifications thereof;  with the proviso that when the cement mixture is calcium sulfate hemihydrate, the pore-forming agent is not calcium sulfate. 12. The bone precursor composition of claim 11, wherein the PLGA has a molecular weight of 5 kD to 100 kD. 13. The bone precursor composition of claim 11, wherein the PLGA has a molecular weight of 10 kD to 30 kD. 14. The bone precursor composition of any one of claims 1 to 3, wherein the cement mixture comprises a mixture of tetracalcium phosphate and dicalcium phosphate anyhydrous;  and the pore-forming agent is selected from the group consisting of PLGA and calcium sulfate. 15. The bone precursor composition of any one of claims 1 to 3, wherein the cement mixture comprises calcium sulfate hemihydrate, and the pore-forming agent is PLGA. 16. The bone precursor composition of any one of claims 1 to 3, further comprising a bioactive agent. 17. The bone precursor composition of claim 16, wherein the bioactive agent is a bone morphogenic protein. 18. The bone precursor composition of claim 16 wherein the bioactive agent is a nucleic acid molecule comprising a sequence encoding a bone morphogenic protein. 19. The bone precursor composition of claim 17, wherein the bone morphogenic protein is selected from the group consisting of OP-1, OP-2, OP-3, COP-1, COP-3, COP-4, COP-5, COP-7, COP-16, BMP-2, BMP-3, BMP-3b, BMP-4, BMP-5, BMP-6, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, BMP-16, BMP-17, BMP-18, GDF-l, GDF-2, GDF-3, GDF-5, GDF-6, GDF-7, GDF-8, GDF-9, GDF-10, GDF-11, GDF-12, MP121, dorsalin-1, DPP, Vg-1, Vgr-1, 60A protein, NODAL, UNIVIN, SCREW, ADMP, NEURAL, TGF-[beta] and conservative amino acid sequence variants thereof having osteogenic activity. 20. The bone precursor composition of claim 16, wherein the bioactive agent is an osteogenic protein comprising an amino acid sequence having at least 70% homology with the C-terminal 102-106 amino acids of human OP-1. 21. The bone precursor composition of claim 16, wherein the bioactive agent is encapsulated in the pore-forming agent. 22. The bone precursor composition according to any one of claims 1 to 3 further comprising a binder. 23. The bone precursor composition of claim 22, wherein the binder is selected from the group consisting of sodium alginate, hyaluronic acid, sodium hyaluronate, gelatin, peptides, mucin, chrondroitin sulfate, chitosan, poloxamer, glycosaminoglycan, polysaccharide, polyethylene glycol, methylcellulose, carboxy methylcellulose, carboxy methylcellulose sodium, carboxy methylcellulose calcium, hydroxypropyl methylcellulose, hydroxybutyl methylcellulose, hydroxyethyl methylcellulose, hydroxyethylcellulose, methylhydroxyethyl cellulose, hydroxyethyl cellulose, mannitol, white petrolatum, mannitol/dextran combinations, mannitol/white petrolatum combinations, sesame oil, fibrin glue, blood and admixtures thereof. 24. The bone precursor composition of any one of claims 1 to 3 that is implantable. 25. A composition comprising a solid cement and a pore-forming agent, wherein the pore-forming agent has a particle size of 20-500 [mu]m and with the proviso that when the pore-forming agent is PLGA, the particle size is 20-140 m or 310 - 500 [mu]m and when the pore forming agent is calcium sulfate, the particle size is 20-140 [mu]m or 260-500 [mu]m. 26. A composition comprising a solid cement and a pore-forming agent, wherein the pore-forming agent has a particle size of 20-140 [mu]m. 27. A composition comprising a solid cement and a pore-forming agent, wherein the pore-forming agent has a particle size of 75-140 [mu]m. 28. The composition of any one of claims 25 to 27, wherein the proportion of pore-forming agent is 7-40% (w/w). 29. The composition of any one of claims 25 to 27, wherein the proportion of pore-forming agent is 725% (w/w). 30. The composition of any one of claims 25 to 27, wherein the pore-forming agent is PLGA and the proportion is 7-14% (w/w). 31. The composition of any one of claims 25 to 27, wherein the solid cement comprises a cement selected from the group consisting of a calcium phosphate cement and a calcium sulfate cement. 32. The composition of any one of claims 25 to 27, wherein the pore-forming agent is a natural or synthetic biodegradable polymer. 33. The composition of any one of claims 25 to 27, wherein the pore-forming agent is selected from the group consisting of ethylenevinylacetate, natural and synthetic collagen, poly(glaxanone), poly(phosphazenes), polyglactin, polyglactic acid, polyaldonic acid, polyacrylic acids, polyalkanoates, polyorthoesters, poly(L-lactide) (PLLA), poly(D,L-lactide) (PDLLA), polyglycolide (PGA), poly(lactide-co-glycolide (PLGA), poly ( -caprolactone), poly(trimethylene carbonate), polyp-dioxanone), poly( -caprolactone-co-glycolide), poly(glycolide-co-trimethylene carbonate) poly(D,L-lactide-co-trimethylene carbonate), polyarylates, polyhydroxybutyrate (PHB), polyanhydrides, poly(anhydride-co-imide) and co-polymers thereof, polymers of amino acids, propylene-co-fumarates, a polymer of one or more a-hydroxy carboxylic acid monomers, calcium sulfate, bioactive glass compositions, admixtures thereof and any derivatives and modifications thereof;  with the proviso that when the cement mixture is calcium sulfate hemihydrate, the pore-forming agent is not calcium sulfate. 34. The composition of claim 33, wherein the PLGA has a molecular weight of 5 kD to 100 kD. 35. The composition of claim 33, wherein the PLGA has a molecular weight of 10 kD to 30 kD. 36. A kit comprising: a) the bone precursor composition of any one of claims 1 to 3;  and b) a bioactive agent. 37. The kit of claim 36, wherein the bioactive agent is a bone morphogenic protein. 38. The kit of claim 36, wherein the bioactive agent is a nucleic acid molecule comprising a sequence encoding a bone morphogenic protein. 39. The kit of claim 37, wherein the bone morphogenic protein is selected from the group consisting of OP-1, OP-2, OP-3, COP-1, COP-3, COP-4, COP-5, COP-7, COP-16, BMP-2, BMP-3, BMP-3b, BMP-4, BMP-5, BMP-6, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, BMP-16, BMP-17, BMP-18., GDF-1, GDF-2, GDF-3, GDF-5, GDF-6, GDF-7, GDF-8, GDF-9, GDF-10, GDF-11, GDF-12, MP121, dorsalin-1, DPP, Vg-1, Vgr-1, 60A protein, NODAL, UNIVIN, SCREW, ADMP, NEURAL, TGF-[beta] and conservative amino acid sequence variants thereof having osteogenic activity. 40. The kit of claim 36, wherein the bioactive agent is an osteogenic protein comprising an amino acid sequence having at least 70% homology with the C-terminal 102-106 amino acids of human OP-1. 41. A kit comprising: a) the bone precursor composition of any one of claims 1 to 3;  and b) a binder. 42. The kit of claim 41, wherein the binder is selected from the group consisting of sodium alginate, hyaluronic acid, sodium hyaluronate, gelatin, peptides, mucin, chrondroitin sulfate, chitosan, poloxamer, glycosaminoglycan, polysaccharide, polyethylene glycol, methylcellulose, carboxy methylcellulose, carboxy methylcellulose sodium, carboxy methylcellulose calcium, hydroxypropyl methylcellulose, hydroxybutyl methylcellulose, hydroxyethyl methylcellulose, hydroxyethylcellulose, methylhydroxyethyl cellulose, hydroxyethyl cellulose, mannitol, white petrolatum, mannitol/dextran combinations, mannitol/white petrolatum combinations, sesame oil, fibrin glue, blood and admixtures thereof. 43. An implantable prosthetic device comprising: a) a prosthetic implant having a surface region implantable adjacent to a target tissue;  and b) the bone precursor composition of any one of claims 1 to 3 disposed on the surface region. 44. The prosthetic device of claim 43 further comprising a bioactive agent dispersed in the bone precursor composition. 45. The prosthetic device of claim 44, wherein the bioactive agent is a bone morphogenic protein. 46. The prosthetic device of claim 44, wherein the bioactive agent is a nucleic acid molecule comprising a sequence encoding a bone morphogenic protein. 47. The prosthetic device of claim 45, wherein the bone morphogenic protein is selected from the group consisting of OP-1, OP-2, OP-3, COP-1, COP-3, COP-4, COP-5, COP-7, COP-16, BMP-2, BMP-3, BMP-3b, BMP-4, BMP-5, BMP-6, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, BMP-16, BMP-17, BMP-18, GDF-1, GDF-2, GDF-3, GDF-5, GDF-6, GDF-7, GDF-8, GDF-9, GDF-10, GDF-11, GDF-12, MP121, dorsalin-1, DPP, Vg-1, Vgr-1, 60A protein, NODAL, UNIVIN, SCREW, ADMP, NEURAL, TGF-[beta] and conservative amino acid sequence variants thereof having osteogenic activity. 48. The prosthetic device of claim 44, wherein the bioactive agent is an osteogenic protein comprising an amino acid sequence having at least 70% homology with the C-terminal 102-106 amino acids of human OP-1. 49. The prosthetic device of claim 43, wherein the device is selected from the group consisting of a hip device, a fusion cage and a maxillofacial device. 50. The prosthetic device of claim 43, wherein the bioactive agent is encapsulated in the pore-forming agent. 51. The prosthetic device of claim 43 further comprising a binder. 52. The prosthetic device of claim 51, wherein the binder is selected from the group consisting of sodium alginate, hyaluronic, acid, sodium hyaluronate, gelatin, peptides, mucin, chrondroitin sulfate, chitosan, poloxamer, glycosaminoglycan, polysaccharide, polyethylene glycol, methylcellulose, carboxy methylcellulose, carboxy methylcellulose sodium, carboxy methylcellulose calcium, hydroxypropyl methylcellulose, hydroxybutyl methylcellulose, hydroxyethyl methylcellulose, hydroxyethylcellulose, methylhydroxyethyl cellulose, hydroxyethyl cellulose, mannitol, white petrolatum, mannitol/dextran combinations, mannitol/white petrolatum combinations, sesame oil, fibrin glue, blood and admixtures thereof. 53. A method of inducing bone formation in a mammal comprising the step of implanting in the defect site of said mammal a composition comprising the bone precursor composition according to any one of claims 1 to 3. 54. The method of claim 53, wherein the composition further comprises a bioactive agent. 55. The method of claim 54, wherein the bioactive agent is a bone morphogenic protein. 56. The method of claim 53, wherein the composition further comprises a binder. 57. A method of delivering a bioactive agent at a site requiring bone formation comprising implanting at the defect site of a mammal a composition comprising the bone precursor composition of claims 1 to 3 and a bioactive agent. 58. The method of claim 57, wherein the bioactive agent is a bone morphogenic protein. 59. The method of claim 57, wherein the bioactive agent is encapsulated in the pore-forming agent. 60. The method of claim 59, wherein the delivery of the bioactive agent is sustained released. 61. The method of claim 57, wherein the bioactive agent is a nucleic acid molecule comprising a sequence encoding a bone morphogenic protein.
法律状态
(CA2460843) LEGAL DETAILS FOR CA2460843  Actual or expected expiration date=2010-08-23    Legal state=DEAD    Status=LAPSED     Event publication date=2002-09-20  Event code=CA/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=CA CA2460843  Application date=2002-09-20  Standardized application number=2002CA-2460843     Event publication date=2003-03-27  Event code=CA/A1  Event type=Examination events  Application laid open  Publication country=CA  Publication number=CA2460843  Publication stage Code=A1  Publication date=2003-03-27  Standardized publication number=CA2460843     Event publication date=2004-06-18  Event code=CA/EEER  Event indicator=Pos  Event type=Examination events  Examination request    Event publication date=2010-08-23  Event code=CA/FZDE  Event indicator=Neg  Event type=Event indicating Not In Force  Dead
专利类型码
A1
国别省市代码
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