Composite bone graft substitute cement and articles produced therefrom
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-033/42
A61K-033/06
출원번호
UP-0530085
(2006-09-08)
등록번호
US-7754246
(2010-08-02)
발명자
/ 주소
Moseley, Jon P.
Carroll, Michael E.
McCanless, Jonathan D.
출원인 / 주소
Wright Medical Technology, Inc.
대리인 / 주소
Womble Carlyle Sandridge & Rice, PLLC
인용정보
피인용 횟수 :
16인용 특허 :
193
초록▼
The invention provides a particulate composition adapted for forming a bone graft substitute cement upon mixing with an aqueous solution, including i) a calcium sulfate hemihydrate powder having a bimodal particle distribution and a median particle size of about 5 to about 20 microns, wherein the ca
The invention provides a particulate composition adapted for forming a bone graft substitute cement upon mixing with an aqueous solution, including i) a calcium sulfate hemihydrate powder having a bimodal particle distribution and a median particle size of about 5 to about 20 microns, wherein the calcium sulfate hemihydrate is present at a concentration of at least about 70 weight percent based on the total weight of the particulate composition; ii) a monocalcium phosphate monohydrate powder; and iii) a β-tricalcium phosphate powder having a median particle size of less than about 20 microns. Bone graft substitute cements made therefrom, a bone graft substitute kit comprising the particulate composition, methods of making and using the particulate composition, and articles made from the bone graft substitute cement are also provided.
대표청구항▼
The invention claimed is: 1. A particulate composition adapted for forming a bone graft substitute cement upon mixing with an aqueous solution, comprising: i) a calcium sulfate hemihydrate powder having a bimodal particle distribution and a median particle size of about 5 to about 20 microns, where
The invention claimed is: 1. A particulate composition adapted for forming a bone graft substitute cement upon mixing with an aqueous solution, comprising: i) a calcium sulfate hemihydrate powder having a bimodal particle distribution and a median particle size of about 5 to about 20 microns, wherein the calcium sulfate hemihydrate is present at a concentration of at least about 70 weight percent based on the total weight of the particulate composition; ii) a monocalcium phosphate monohydrate powder; and iii) a β-tricalcium phosphate powder having a median particle size of less than about 20 microns. 2. The particulate composition of claim 1, further comprising β-tricalcium phosphate granules having a median particle size of at least about 75 microns. 3. The particulate composition of claim 2, wherein the β-tricalcium phosphate granules have a median particle size of about 75 to about 1,000 microns. 4. The particulate composition of claim 2, wherein the β-tricalcium phosphate granules are present at a concentration of up to about 20 weight percent based on the total weight of the particulate composition. 5. The particulate composition of claim 4, wherein the β-tricalcium phosphate granules are present at a concentration of up to about 12 weight percent based on the total weight of the particulate composition. 6. The particulate composition of claim 1, wherein the calcium sulfate hemihydrate is α-calcium sulfate hemihydrate. 7. The particulate composition of claim 1, wherein the calcium sulfate hemihydrate powder has a bimodal particle distribution comprising about 30 to about 60 volume percent of particles having a mode of about 1.0 to about 3.0 microns and about 40 to about 70 volume percent of particles having a mode of about 20 to about 30 microns, based on the total volume of the calcium sulfate hemihydrate powder. 8. The particulate composition of claim 1, wherein the calcium sulfate hemihydrate is present at a concentration of at least about 75 weight percent. 9. The particulate composition of claim 1, wherein the combined concentration of the monocalcium phosphate monohydrate powder and the β-tricalcium phosphate powder is about 3 to about 30 weight percent based on the total weight of the particulate composition. 10. The particulate composition of claim 1, wherein the β-tricalcium phosphate powder has a bimodal particle size distribution comprising about 30 to about 70 volume percent of particles having a mode of about 2.0 to about 6.0 microns and about 30 to about 70 volume percent of particles having a mode of about 40 to about 70 microns based on the total volume of the β-tricalcium phosphate powder. 11. The particulate composition of claim 10, wherein the β-tricalcium phosphate powder has a bimodal particle size distribution comprising about 50 to about 65 volume percent of particles having a mode of about 4.0 to about 5.5 microns and about 35 to about 50 volume percent of particles having a mode of about 60 to about 70 microns based on the total volume of the β-tricalcium phosphate powder. 12. The particulate composition of claim 1, further comprising an accelerant adapted for accelerating the conversion of calcium sulfate hemihydrate to calcium sulfate dihydrate. 13. The particulate composition of claim 12, wherein the accelerant is selected from the group consisting of calcium sulfate dihydrate particles, potassium sulfate particles, and sodium sulfate particles, wherein the accelerant is optionally coated with sucrose. 14. The particulate composition of claim 12, wherein the accelerant is present at a concentration of up to about 1 weight percent based on the total weight of the particulate composition. 15. The particulate composition of claim 1, further comprising a biologically active agent. 16. The particulate composition of claim 15, wherein the biologically active agent is selected from the group consisting of cancellous bone chips, growth factors, antibiotics, pesticides, chemotherapeutic agents, antivirals, analgesics, and anti-inflammatory agents. 17. The particulate composition of claim 15, wherein the biologically active agent is an osteoinductive material. 18. The particulate composition of claim 17, wherein the osteoinductive material is demineralized bone matrix. 19. The particulate composition of claim 15, wherein the biologically active agent is a growth factor selected from the group consisting of fibroblast growth factors, platelet-derived growth factors, bone morphogenic proteins, osteogenic proteins, transforming growth factors, LIM mineralization proteins, osteoid-inducing factors, angiogenins, endothelins; growth differentiation factors, ADMP-1, endothelins, hepatocyte growth factor and keratinocyte growth factor, heparin-binding growth factors, hedgehog proteins, interleukins, colony-stimulating factors, epithelial growth factors, insulin-like growth factors, cytokines, osteopontin, and osteonectin. 20. The particulate composition of claim 1, wherein the particulate composition sets to a hardened mass upon mixing with an aqueous solution in about 3 to about 25 minutes. 21. A bone graft substitute cement comprising the reaction product formed by mixing a particulate composition according to claim 1 with an aqueous solution, the reaction product comprising calcium sulfate dihydrate and brushite. 22. The bone graft substitute cement of claim 21, wherein said cement is cast in a predetermined shape. 23. The bone graft substitute cement of claim 22, wherein said predetermined shape is selected from the group consisting of pellets, granules, wedges, blocks, and disks. 24. The bone graft substitute cement of claim 21, wherein said cement exhibits a diametral tensile strength of at least about 4 MPa after curing for one hour in ambient air following mixing of the particulate composition with the aqueous solution. 25. The bone graft substitute cement of claim 24, wherein said cement exhibits a diametral tensile strength of at least about 6 MPa after curing for one hour in ambient air. 26. The bone graft substitute cement of claim 21, wherein said cement exhibits a diametral tensile strength of at least about 8 MPa after curing for 24 hours in ambient air following mixing of the particulate composition with the aqueous solution. 27. The bone graft substitute cement of claim 26, wherein said cement exhibits a diametral tensile strength of at least about 10 MPa after curing for 24 hours in ambient air. 28. The bone graft substitute cement of claim 21, wherein said cement exhibits an average dissolution rate, expressed as an average percentage of weight loss per day, that is at least about 25% lower than the average dissolution rate of a cement formed using a particulate composition consisting of calcium sulfate, the average dissolution rate measured by immersion of a 4.8 mm OD pellet having a length of 3.3 mm in distilled water at 37° C. 29. The bone graft substitute cement of claim 28, wherein said cement exhibits an average dissolution rate that is at least about 30% lower than a cement formed using a particulate composition consisting of calcium sulfate only. 30. The bone graft substitute cement of claim 21, wherein the aqueous solution comprises a carboxylic acid. 31. The bone graft substitute cement of claim 30, wherein the carboxylic acid is a hydroxy carboxylic acid. 32. The bone graft substitute cement of claim 31, wherein the hydroxy carboxylic acid is glycolic acid. 33. The bone graft substitute cement of claim 30, wherein the carboxylic acid is neutralized to a pH of about 6.5 to about 7.5. 34. A bone graft substitute kit, comprising one or more containers enclosing a particulate composition according to claim 1, a separate container enclosing a sterile aqueous solution, and a written instruction set describing a method of using said kit. 35. The bone graft substitute kit of claim 34, further comprising a mixing apparatus adapted for mixing the particulate composition and the aqueous solution. 36. The bone graft substitute kit of claim 34, further comprising a delivery device adapted for delivering a bone graft substitute cement mixture to the site of a bone defect. 37. A method for treating a bone defect, comprising applying a bone graft substitute cement according to claim 21 to the site of the bone defect. 38. A particulate composition adapted for forming a bone graft substitute cement upon mixing with an aqueous solution, comprising: i) a calcium sulfate hemihydrate powder having a bimodal particle distribution and a median particle size of about 5 to about 20 microns, wherein the calcium sulfate hemihydrate is present at a concentration of at least about 75 weight percent based on the total weight of the particulate composition; ii) a monocalcium phosphate monohydrate powder; iii) a β-tricalcium phosphate powder having a median particle size of less than about 20 microns, the monocalcium phosphate monohydrate powder and the β-tricalcium phosphate powder being present at a combined concentration of about 3 to about 30 weight percent based on the total weight of the particulate composition; iv) β-tricalcium phosphate granules having a median particle size of at least about 75 microns and present at a concentration of up to about 20 weight percent based on the total weight of the particulate composition; and v) an accelerant adapted for accelerating the conversion of calcium sulfate hemihydrate to calcium sulfate dihydrate, the accelerant being present at a concentration of up to about 1 weight percent based on the total weight of the particulate composition. 39. The particulate composition of claim 38, further comprising a biologically active agent. 40. The particulate composition of claim 39, wherein the biologically active agent is selected from the group consisting of cancellous bone chips, growth factors, antibiotics, pesticides, chemotherapeutic agents, antivirals, analgesics, and anti-inflammatory agents. 41. The particulate composition of claim 39, wherein the biologically active agent is an osteoinductive material. 42. The particulate composition of claim 41, wherein the osteoinductive material is demineralized bone matrix. 43. The particulate composition of claim 39, wherein the biologically active agent is a growth factor selected from the group consisting of fibroblast growth factors, platelet-derived growth factors, bone morphogenic proteins, osteogenic proteins, transforming growth factors, LIM mineralization proteins, osteoid-inducing factors, angiogenins, endothelins; growth differentiation factors, ADMP-1, endothelins, hepatocyte growth factor and keratinocyte growth factor, heparin-binding growth factors, hedgehog proteins, interleukins, colony-stimulating factors, epithelial growth factors, insulin-like growth factors, cytokines, osteopontin, and osteonectin. 44. A bone graft substitute cement comprising β-tricalcium phosphate granules and a reaction product formed by mixing a particulate composition according to claim 38 with an aqueous solution, the reaction product comprising calcium sulfate dihydrate and brushite. 45. A bone graft substitute kit, comprising one or more containers enclosing a particulate composition according to claim 38, a separate container enclosing a sterile aqueous solution, and a written instruction set describing a method of using the kit. 46. A method for treating a bone defect, comprising applying a bone graft substitute cement according to claim 44 to the site of the bone defect. 47. A particulate composition adapted for forming a bone graft substitute cement upon mixing with an aqueous solution, comprising: i) an α-calcium sulfate hemihydrate powder having a bimodal particle distribution and a median particle size of about 5 to about 20 microns, wherein the calcium sulfate hemihydrate is present at a concentration of at least about 75 weight percent based on the total weight of the particulate composition, and wherein the calcium sulfate hemihydrate powder has a bimodal particle distribution comprising about 30 to about 60 volume percent of particles having a mode of about 1.0 to about 3.0 microns and about 40 to about 70 volume percent of particles having a mode of about 20 to about 30 microns, based on the total volume of the calcium sulfate hemihydrate powder; ii) a monocalcium phosphate monohydrate powder; iii) a β-tricalcium phosphate powder having a median particle size of less than about 20 microns, the monocalcium phosphate monohydrate powder and the β-tricalcium phosphate powder being present at a combined concentration of about 10 to about 20 weight percent based on the total weight of the particulate composition; iv) β-tricalcium phosphate granules having a median particle size of about 100 to about 400 microns and present at a concentration of up to about 12 weight percent based on the total weight of the particulate composition; and v) an accelerant adapted for accelerating the conversion of calcium sulfate hemihydrate to calcium sulfate dihydrate, the accelerant being present at a concentration of up to about 1 weight percent based on the total weight of the particulate composition. 48. The particulate composition of claim 47, further comprising a biologically active agent is selected from the group consisting of cancellous bone chips, growth factors, antibiotics, pesticides, chemotherapeutic agents, antivirals, analgesics, and anti-inflammatory agents. 49. The particulate composition of claim 48, wherein the biologically active agent is a growth factor selected from the group consisting of fibroblast growth factors, platelet-derived growth factors, bone morphogenic proteins, osteogenic proteins, transforming growth factors, LIM mineralization proteins, osteoid-inducing factors, angiogenins, endothelins; growth differentiation factors, ADMP-1, endothelins, hepatocyte growth factor and keratinocyte growth factor, heparin-binding growth factors, hedgehog proteins, interleukins, colony-stimulating factors, epithelial growth factors, insulin-like growth factors, cytokines, osteopontin, and osteonectin. 50. The particulate composition of claim 47, further comprising an osteoinductive material. 51. The particulate composition of claim 50, wherein the osteoinductive material is demineralized bone matrix. 52. A bone graft substitute cement comprising β-tricalcium phosphate granules and a reaction product formed by mixing a particulate composition according to claim 47 with an aqueous solution, the reaction product comprising calcium sulfate dihydrate and brushite. 53. A bone graft substitute kit, comprising one or more containers enclosing a particulate composition according to claim 47, a separate container enclosing a sterile aqueous solution, and a written instruction set describing a method of using the kit. 54. A method for treating a bone defect, comprising applying a bone graft substitute cement according to claim 47 to the site of the bone defect. 55. A particulate composition adapted for forming a bone graft substitute cement upon mixing with an aqueous solution, comprising: i) a calcium sulfate hemihydrate powder having a bimodal particle distribution and a median particle size of about 5 to about 20 microns, wherein the calcium sulfate hemihydrate powder comprises about 30 to about 60 volume percent of particles having a mode of about 1.0 to about 3.0 microns and about 40 to about 70 volume percent of particles having a mode of about 20 to about 30 microns, based on the total volume of the calcium sulfate hemihydrate powder; ii) a monocalcium phosphate monohydrate powder; iii) a β-tricalcium phosphate powder having a median particle size of less than about 20 microns; iv) an accelerant adapted for accelerating the conversion of calcium sulfate hemihydrate to calcium sulfate dihydrate; and v) demineralized bone matrix.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (193)
Stevenson Sharon ; Gertzman Arthur A., Allograft tissue material for filling spinal fusion cages or related surgical spaces.
Bennett Steven L. (Southington CT) Jiang Ying (North Haven CT) Gruskin Elliott A. (Killingworth CT) Connolly Kevin M. (Hamden CT), Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured theref.
Genge, Brian R.; Wu, Licia; Sauer, Glenn R.; Wuthier, Roy E.; Genge, Ronald, Biocompatible cement containing reactive calcium phosphate nanoparticles and methods for making and using such cement.
Norton Richard L. (Fort Collins CO) Knight Stephen Michael Gregory (Fort Collins CO) Tipton Arthur J. (Birmingham AL), Biodegradable polymeric composition.
Cooke Francis W. (Wichita KS) Marrero Thomas R. (Columbia ; MO) Yasuda Hirotsuga K. (Columbia ; MO), Bone cement having chemically joined reinforcing fillers.
Riess Guido (Garmisch-Partenkirchen DEX) Geiger Albert (Garmisch-Partenkirchen DEX), Bone implant member for prostheses and bone connecting elements and process for the production thereof.
Chae, Soo Kyung; Kim, Hong Yeoul; Lee, Ho Yeon; Lee, Chang Hun; Seo, Kang Moon, Calcium phosphate artificial bone as osteoconductive and biodegradable bone substitute material.
Liu Sung-Tsuen (29 Landing Laguna Niguel CA 92677) Chung Harvey H. (43 Via Costa Verde Rancho Palos Verdes CA 90274), Calcium phosphate calcium sulfate composite implant material.
Ducheyne Paul (Bryn Mawr PA) Cuckler John (Haverford PA) Radin Shulamit (Cherry Hill NJ), Calcium phosphate ceramics for bone tissue calcification enhancement.
Takagi Shigehide (Tokyo JPX) Ito Kuniomi (Tochigi-ken JPX) Hidaka Tsuneo (Tokyo JPX), Ceramic device providing an environment for the promotion and formation of new bone.
Brown Walter E. (Rockville MD) Chow Laurence C. (Germantown MD), Combinations of sparingly soluble calcium phosphates in slurries and pastes as mineralizers and cements.
Hermansson Leif (Uppsala SEX) Forberg Sevald (Enskede SEX) Jiangou Li (Stockholm SEX), Composite ceramic material and method to manufacture the material.
Rhee Woonza (Palo Alto CA) Wallace Donald G. (Menlo Park CA) Michaels Alan S. (Boston MA) Burns ; Jr. Ramon A. (Fremont CA) Fries Louis (Los Altos CA) DeLustro Frank (Belmont CA) Bentz Hanne (Newark , Composition for bone repair.
Randolph Donald A. (Wheaton IL) Negri Jodi L. (Lakevilla IL) Devine Timothy R. (Whitefish Bay WI) Gitelis Steven (Oakbrook IL), Controlled dissolution pellet containing calcium sulfate.
Kronenthal Richard L. (Fair Lawn NJ) Mattei Frank V. (Piscataway NJ) Levy Alan (Bridgewater NJ), Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition.
Kronenthal Richard L. (Fair Lawn NJ) Mattei Frank V. (Piscataway NJ) Levy Alan J. (Bridgewater NJ), Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition.
Prewett Annamarie B. (Little Silver NJ) Stikeleather Roger C. (Doylestown PA), Demineralized bone particles and flowable osteogenic composition containing same.
Chu George H. ; Yeung Jeff E. ; Schroeder Jacqueline Anne ; Shenoy Vivek N. ; Brown Melissa K. C. ; Cassidy James J. ; Rice John, Devices for tissue repair and methods for preparation and use thereof.
Yim Kalvin W. K. (N. andover MA) Huberty Michael C. (Andover MA) Northey ; Jr. Richard P. (Ipswich MA) Schrier Jay A. (Andover MA), Formulations for delivery of osteogenic proteins.
Ricci John ; Alexander Harold ; Berman Charles L. ; Frenkel Sally ; Hollander Bruce ; Pecora Gabriele,ITX, Implantation of surgical implants with calcium sulfate.
Constantz Brent R. (Scott Valley CA) Barr Bryan (Mountain View CA) McVicker Kevin (Fremont CA), Intimate mixture of calcium and phosphate sources as precursor to hydroxyapatite.
Polson Alan M. ; Swanbom Deryl D. ; Dunn Richard L. ; Cox Charles P. ; Norton Richard L. ; Lowe Bryan K. ; Peterson Kenneth S., Method and composition for treating a bone tissue defect.
Barlow Joel W. (7139 Valburn Dr. Austin TX 78731) Lee Goonhee (3357 Lake Austin Blvd. #C Austin TX 78703) Crawford Richard H. (912 Lipan Trail Austin TX 78733) Beaman Joseph J. (700 Texas Ave. Austin, Method for fabricating artificial bone implant green parts.
Ducheyne Paul (Bryn Mawr PA) Cuckler John (Haverford PA) Radin Shulamit (Cherry Hill NJ), Method of depositing calcium phosphate cermamics for bone tissue calcification enhancement.
Lee Dosuk D. ; Rey Christian,FRX ; Aiolova Maria ; Tofighi Aliassghar, Methods and products related to the physical conversion of reactive amorphous calcium phosphate.
Hanker Jacob S. (Chapel Hill NC) Terry Bill C. (Chapel Hill NC) Ambrose Wallace W. (Chapel Hill NC) Lupton Cecel R. (Chapel Hill NC), Plaster of Paris as a bioresorbable scaffold in implants for bone repair.
Matthews Frank D. ; Caldarise Salvatore, Precision powder injection molded implant with preferentially leached texture surface and method of manufacture.
Prewett Annamarie B. (Little Silver NJ) Stikeleather Roger C. (Doylestown PA), Process for producing flowable osteogenic composition containing demineralized bone particles.
Saita Kenji (Toyonaka JPX) Miyazaki Susumu (Ibaraki JPX), Process for production of ceramic shaped product having granule layer on the surface and ceramic implant material.
Sonuparlak Birol (Seattle WA) Aksay Ilhan A. (Seattle WA), Process for the production of porous ceramics using decomposable polymeric microspheres and the resultant product.
Broemer Heinz (Hermannstein DEX) Adam Werner (Hermannstein DEX) Hedrich Friedhelm (Edingen DEX), Prosthesis parts provided with a coating of a bio-active material.
Broemer Heinz (Hermannstein DEX) Adam Werner (Hermannstein DEX) Hedrich Friedhelm (Edingen DEX), Prosthesis parts provided with a coating of a bio-active material, process of making same, and method of using them for.
Glowczewskie ; Jr. Frank P. (Gainesville IL) Present David A. (New York NY) Anderson David W. (New York NY) McBrayer Patrick A. (Yardley PA), Reconstitution of human bone and tissue.
Liu Sung-Tsuen (29 Landing Laguna Niguel CA 92677) Chung Harvey H. (43 Via Costa Verde Rancho Palos Verdes CA 90274), Resorbable bioactive calcium phosphate cement.
Liu Sung-Tsuen (29 Landing Laguna Niguel CA 92677) Chung Harvey H. (43 Via Costa Verde Rancho Palos Verdes CA 90274), Resorbable bioactive phosphate containing cements.
Prewett Annamarie B. (Little Silver NJ) Stikeleather Roger C. (Doylestown PA) Bogdansky Simon (Marlboro NJ) O\Leary Robert K. (Spring Lake NJ), Shaped, swollen demineralized bone and its use in bone repair.
Prewett Annamarie B. (Little Silver NJ) Stikeleather Roger C. (Doylestown PA) Bogdansky Simon (Marlboro NJ) O\Leary Robert K. (Spring Lake NJ), Shaped, swollen demineralized bone and its use in bone repair.
Farris Edward T. (4715 Greenville Ave. Dallas TX 75206) Barsa John J. (60 Haven Ave. New York NY 10032) Lagow Richard J. (6204 Shadow Mountain Dr. Austin TX 78731) Capano Paul J. (1730 E. Oltorf Aust, Solid calcium phosphate materials.
Ison Ira C. (Campbell CA) Fulmer Mark T. (San Jose CA) Barr Bryan M. (San Jose CA) Constantz Brent R. (Los Gatos CA), Storage stable calcium phosphate cements.
Duquet Bruno (Lille FRX) Daculsi Guy (Vigneux De Bretagne FRX) Delecrin Joel (Nantes FRX), Surface coating for prosthesis system containing HA/TCP composition.
Bogdansky Simon (Marlboro NJ) O\Leary Robert K. (Spring Lake NJ), Swollen demineralized bone particles, flowable osteogenic composition containing same and use of the composition in the.
Harney Marilyn J. (Painesville OH) Vauss ; Jr. Elvin M. (Cleveland OH) Sane Ajit Y. (Willoughby OH), Titanium and titanium hydride reticulates and method for making.
Patat Jean-Louis (Paris FRX) Cirotteau Yves (Paris FRX), Use of particles of a biocompatible and bioabsorbable calcium salt as active ingredient in the preparation of a medicina.
Barrett, Stephen Douglas; Ciske, Fred Lawrence; Colombo, Joseph Michael; Endres, Gregory William; Germain, Bradlee David; Kornilov, Andriy; Kramer, James Bernard; Uzieblo, Adam; Owen, Thomas Allen; O'Malley, James Paul, Difluorolactam compositions for EP4-mediated osteo related diseases and conditions.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.