IPC분류정보
국가/구분 |
United States(US) Patent
등록
|
국제특허분류(IPC7판) |
|
출원번호 |
US-0589226
(2005-01-27)
|
등록번호 |
US-8333985
(2012-12-18)
|
국제출원번호 |
PCT/US2005/003092
(2005-01-27)
|
§371/§102 date |
20061220
(20061220)
|
국제공개번호 |
WO2005/072656
(2005-08-11)
|
발명자
/ 주소 |
- Knaack, David
- Diegmann, Michele
- Manrique, Albert
- Benham, Keyvan
|
출원인 / 주소 |
|
인용정보 |
피인용 횟수 :
12 인용 특허 :
206 |
초록
▼
A demineralized bone matrix (DBM) or other matrix composition is provided that has been stabilized by lowering the pH of the composition, reducing the water content, adding water substitutes, and/or increasing the amount of deuterated water present in the composition in order to reduce the activity
A demineralized bone matrix (DBM) or other matrix composition is provided that has been stabilized by lowering the pH of the composition, reducing the water content, adding water substitutes, and/or increasing the amount of deuterated water present in the composition in order to reduce the activity of endogenous degrading enzymes such as proteases. A hydrated form of a stabilized DBM composition may be stable up to a year at room temperature at acidic pH. The acidified DBM compositions may be further stabilized by the addition of a stabilizing agent such as deuterated water, water substitutes, polymers, protease inhibitors, glycerol or hydrogels.
대표청구항
▼
1. A demineralized bone matrix composition comprising: demineralized bone matrix; andat least one non-glycercol stabilizing means;wherein the composition retains at least 50% of its original osteoinductivity after one year at room temperature, andwherein the non-glycerol stabilizing means is a non-g
1. A demineralized bone matrix composition comprising: demineralized bone matrix; andat least one non-glycercol stabilizing means;wherein the composition retains at least 50% of its original osteoinductivity after one year at room temperature, andwherein the non-glycerol stabilizing means is a non-glycerol polyol selected from the group consisting of polynivyl alcohols and polyethylene glycols. 2. The composition of claim 1, wherein the composition does not include glycerol. 3. The composition of claim 1, wherein the demineralized bone matrix is in the form selected from the group consisting fibers, plates, particles, threads, and gels. 4. The composition of claim 1 further comprising water. 5. The composition of claim 1 further comprising hyaluronic acid. 6. The composition of claim 1, wherein the non-glyercol stabilizing means is a protease inhibitor or combination of protease inhibitors. 7. The composition of claim 6, wherein the protease inhibitor is selected from the group consisting of aprotinin, 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), amastatin-HCl, alpha1-antichymotrypsin, antithrombin III, alpha1-antitrypsin, 4-aminophenylmethane sulfonyl-fluoride (APMSF), arphamenine A, arphamenine B, E-64, bestatin, CA-074, CA-074-Me, calpain inhibitor I, calpain inhibitor II, cathepsin inhibitor, chymostatin, diisopropylfluorophosphate (DFP), dipeptidylpeptidase IV inhibitor, diprotin A, E-64c, E-64d, E-64, ebelactone A, ebelactone B, EGTA, elastatinal, foroxymithine, hirudin, leuhistin, leupeptin, alpha2-macroglobulin, phenylmethylsulfonyl fluoride (PMSF), pepstatin A, phebestin, 1,10-phenanthroline, phosphoramidon, chymostatin, benzamidine HCl, antipain, epsilon-aminocaproic acid, N-ethylmaleimide, trypsin inhibitor, 1-chloro-3-tosylamido-7-amino-2-heptanone (TLCK), 1-chloro-3-tosylamido-4-phenyl-2-butanone (TPCK), trypsin inhibitor, sodium EDTA, and combinations thereof. 8. The composition of claim 1, wherein the pH of the composition is below 7. 9. The composition of claim 1, wherein the pH of the composition is below 5. 10. The composition of claim 1, wherein the pH of the composition is below 4. 11. The composition of claim 1, wherein the pH of the composition is below 2. 12. The composition of claim 1, wherein the pH of the composition is between approximately 3 and 4. 13. The composition of claim 1, wherein the pH of the composition is between approximately 4 and 5. 14. The composition of claim 1, wherein the composition retains at least 75% of its original osteoinductivity after 1 year at room temperature. 15. The composition of claim 1, wherein the composition retains at least 90% of its original osteoinductivity after 1 year at room temperature. 16. The composition of claim 1, wherein the composition retains at least 75% of its original osteoinductivity after 2 years at room temperature. 17. The composition of claim 1, wherein the composition retains at least 90% of its original osteoinductivity after 2 years at room temperature. 18. The composition of claim 1 further comprising at least one exogenous osteoinductive or osteogenic agent. 19. The composition of claim 1 further comprising: a non-glycerol carrier. 20. The composition of claim 19, wherein the carrier is selected from the group consisting of hyaluronic acid, collagens, lipids, polymers, proteins, and water. 21. The composition of claim 19, wherein the carrier is selected from the group consisting of hyaluronic acid, collagens, lipids, polymers, and water. 22. The composition of claim 19, wherein the carrier is selected from the group consisting of deuterated water (D2O), protease inhibitors, non-glycerol polyols, sorbitol, and acids. 23. A demineralized bone matrix composition comprising: an exogenous destabilizing agent. 24. The composition of claim 23, wherein the exogenous destabilizing agent is a protease. 25. The composition of claim 23, wherein the exogenous destabilizing agent is a tissue comprising a protease.
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