New hydroxapatite calcium phosphates, their method of preparation and their applications 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2005115418 A2 2005-12-08 [WO2005115418]WO2005115418 A9 2006-03-09 [WO2005115418]WO2005115418 A3 2007-06-07 [WO2005115418] / 2005-12-082006-03-092007-06-07
申请号/申请日
2005WO-US15684 / 2005-05-06
发明人
GODBER JOHN;LEITE LORRAINE;
申请人
INNOPHOS;
主分类号
IPC分类号
A01N-059/22A01N-059/26A61K-009/14A61K-009/16A61K-009/20A61K-033/36A61K-033/42A61K-047/02C01B-025/16C01B-025/26C01B-025/32
摘要
(WO2005115418) The present invention is directed to calcium phosphates in granular form having an X-ray diffraction pattern characteristic of hydroxyapatite in which a portion of the anions of the crystal lattice are substituted with carbonate anions and which have good compressibility and flow properties in direct compression applications.  The invention is also directed to the methods for preparing the calcium phosphate aforesaid granules characterized in that the methods include the processing of a brushite dicalcium phosphate solution having a specified particle size distribution using a solution of an alkaline earth carbonate for a sufficient period of time to allow the transformation of the brushite calcium phosphate into hydroxyapatite calcium phosphate.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2004FR-0004900 2004-05-06
主权利要求
(WO2005115418) CLAIMS 1. A composition comprising calcium phosphate in granular form having an X-ray diffraction pattern characteristic of hydroxyapatite in which up to 10% of the phosphate anions of the crystal lattice are substituted with carbonate anions, and having a particle size such that at least 90% of the particles are larger than 10 microns and at least 90% of the particles are smaller than 260 microns. 2. The composition of claim 1, wherein the size of the calcium phosphate granules expressed by the median diameter (dso) is between 100 μm and 250 μm. 3. The composition of claim 1 , wherein the apparent non-compacted density of the granules is at least 0.6. 4. The composition of claim 1 , wherein the apparent non-compacted density of the granules is between about 0.68 and about 0.72. 5. The composition of claim 1, wherein the apparent compacted density of the granules is at least 0.7. 6. The composition of claim 1 , wherein the apparent compacted density of the granules is between about 0.76 and about 0.82. 7. The composition of claim 1, wherein the granules have an instantaneous flow index greater than about 7. 8. The composition of claim 1, wherein the granules have the following compressibility profile: - from 15 to 40 KPa for compression of 30 KN, - from 7 to 25 KPa for compression of 20 KN, - from 3 to 10 KPa for compression of 10 KN. 9. The composition of claim 1, wherein the granules have a disintegration speed in water of less than 60 seconds. 10. The composition of claim 1, characterized in that it satisfies the following formula: Caio(Pθ4)6(OH)2-2x(Cθ3)χ in which x is between 0 and 1. 11. The composition of claim 1 , characterized in that it satisfies the following formula: Ca6M4(PO4MOH)2-2X(CO3)X in which M represents an alkaline earth cation other than calcium and x is between O and 1. 12. The composition of claim 11, wherein M is magnesium. 13. The composition of claim 1, wherein between about 3% and about 6% of the phosphate anions of the crystal lattice are substituted with carbonate anions. 14. A method of preparing a calcium phosphate in granular form with an X-ray diffraction pattern characteristic of hydroxyapatite comprising the steps of: providing an aqueous suspension of brushite dicalcium phosphate in an appropriate vessel; adding to the brushite suspension a solution of an alkaline earth carbonate base; and mixing the suspension for a sufficient amount of time to allow the transformation of the bτπshttexaicτuτrrp1io^tøteintcrhydroxyapatite calcium phosphate. 15. The method of claim 14, wherein the brushite dicalcium phosphate has a particle size distribution such that the median diameter (dso) is between 100 μm and 250 μm. 16. The method of claim 15, wherein the carbonate base is selected from the group consisting of calcium carbonate, magnesium carbonate, and mixtures thereof. 17. The method of claim 16, further comprising the step of maintaining the suspension of brushite and carbonate base at a pH of greater than or equal to 6.0. 18. The method of claim 17, further comprising the step of heating the suspension of brushite and carbonate base at a temperature of greater than about 5O0C. 19. The method of claim 18, wherein the suspension of brushite and carbonate base is heated to a temperature of about 900C. 20. The method of claim 18, wherein the quantity of carbonate base used is such that it represents from about 80% to about 110% of the stoichiometric quantity expressed with respect to the brushite calcium phosphate in the suspension. 21. The method of claim 20, further comprising the step of separating the hydroxyapatite calcium phosphate from the aqueous solution by filtration or centrifugation. 22. The method of claim 21 , further comprising the step of drying the hydroxyapatite calcium phosphate is at a temperature of between about 80 and about 12O0C. 23. Calcium phosphate in granular form with an X-ray diffraction pattern characteristic of hydroxyapatite obtained using the method of claim 22. 24. A tablet for use in administering an active ingredient comprising and active ingredient and a matrix having hydroxyapatite calcium phosphate in granular form obtained by the method of claim 22. 25. The tablet of claim 24, wherein the hydroxyapatite calcium phosphate comprises at least 80% of the weight of the matrix. 26. The tablet of claim 24, wherein the tablets comprise the active ingredient in an amount of between 0.001% and 95% by weight of the total composition. 27. The tablet of claim 24, further comprising about 0.5% by weight magnesium stearate. 28. The tablet of claim 27, further comprising between about 5% to about 10% by weight of a disintegrating agent. 29. The tablet of claim 28, wherein the disintegrating agent is a starch or croscamellose sodium. 30. The tablet of claim 24, wherein the friability of the tablet is less than 1%. 31. The tablet of claim 30, wherein the tablet has a disintegration time of less than 1 minute.
法律状态
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专利类型码
A2A9A3
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