Nanocrystalline apatites and composites, prostheses incorporating them, and method for their production

Abstract

Methods for synthesis of nanocrystalline apatites are presented, as well as a series of specific reaction parameters that can be adjusted to tailor, in specific ways, properties in the recovered product. Particulate apatite compositions having average crystal size of less than 150 nm are provided. Products also can have a surface area of at least 40 m 2 /g and can be of high density. Hydroxy apatite material is investigated in particular detail. Compositions of the invention can be used as prosthetic implants and coatings for prosthetic implants.

1. A composition, comprising particulate apatite having an average apatite crystal size of less than 100 nm, wherein the crystal is spherical. 
     
     
       2. The composition of  claim 1  comprising particulate apatite having an average apatite crystal size of less than 50 nm. 
     
     
       3. The composition of  claim 1  comprising particulate apatite having an average apatite crystal size of less than 30 nm. 
     
     
       4. The composition of  claim 1  comprising particulate apatite having an average apatite crystal size of less than 20 nm. 
     
     
       5. A composition as in  claim 1  wherein the particulate apatite is densified. 
     
     
       6. The composition of  claim 1  comprising apatite having an average particle size of less than 1 μm. 
     
     
       7. The composition of  claim 1  comprising apatite having an average particle size of less than 0.5 μm. 
     
     
       8. The composition of  claim 1  comprising apatite having an average particle size of less than 0.25 μm. 
     
     
       9. A composition comprising particulate apatite having a surface area of at least 40 m 2 /g and a spherical crystal. 
     
     
       10. The composition of  claim 7  comprising particulate apatite having a surface area of at least 100 m 2 /g. 
     
     
       11. The composition of  claim 9  comprising particulate apatite having a surface area of at least 150 m 2 /g. 
     
     
       12. The composition of  claim 9  that undergoes apatite phase decomposition of less than 10% when exposed to conditions of at least 1000° C. for at least 2 hours. 
     
     
       13. The composition of  claim 12  that undergoes apatite phase decomposition of less than 5% when exposed to conditions of at least 1000° C. for at least 2 hours. 
     
     
       14. The composition of  claim 12  that undergoes apatite phase decomposition of less than 3% when exposed to conditions of at least 1000° C. for at least 2 hours. 
     
     
       15. The composition of  claim 12  that undergoes apatite phase decomposition of less than 10% when exposed to conditions of at least 1100° C. for at least 2 hours. 
     
     
       16. The composition of  claim 12  that undergoes apatite phase decomposition of less than 5% when exposed to conditions of at least 1100° C. for at least 2 hours. 
     
     
       17. The composition of  claim 12  that undergoes apatite phase decomposition of less than 3% when exposed to conditions of at least 1100° C. for at least 2 hours. 
     
     
       18. The composition of  claim 12  that undergoes apatite phase decomposition of less than 10% when exposed to conditions of at least 1200° C. for at least 2 hours. 
     
     
       19. The composition of  claim 12  that undergoes apatite phase decomposition of less than 5% when exposed to conditions of at least 1200° C. for at least 2 hours. 
     
     
       20. The composition of  claim 12  that undergoes apatite phase decomposition of less than 3% when exposed to conditions of at least 1200° C. for at least 2 hours. 
     
     
       21. The composition of  claim 12  that undergoes apatite phase decomposition of less than 10% when exposed to conditions of at least 1300° C. for at least 2 hours. 
     
     
       22. The composition of  claim 12  that undergoes apatite phase decomposition of less than 5% when exposed to conditions of at least 1300° C. for at least 2 hours. 
     
     
       23. The composition of  claim 12  that undergoes apatite phase decomposition of less than 3% when exposed to conditions of at least 1300° C. for at least 2 hours. 
     
     
       24. An article having a dimension of at least 0.5 cm made up of the composition of  claim 1 . 
     
     
       25. The article of  claim 24  wherein the particulate apatite is consolidated. 
     
     
       26. The article of  claim 24 , formed into the shape of a prosthesis. 
     
     
       27. The article of  claim 24  that is a prosthesis. 
     
     
       28. The article of  claim 24  comprising an exterior coating on a prosthesis. 
     
     
       29. The article of  claim 28  comprising an exterior coating, on a prosthesis, of at least 0.5 micron in thickness. 
     
     
       30. The article of  claim 24  having a theoretical density of at least 90%. 
     
     
       31. The article of  claim 24  having a theoretical density of at least 95%. 
     
     
       32. The article of  claim 24  having a theoretical density of at least 98%. 
     
     
       33. An article having a dimension of at least 0.5 cm made up of the composition of  claim 9 . 
     
     
       34. The article of  claim 33  having a porosity of at least 20%. 
     
     
       35. The article of  claim 33  having a porosity of at least 30%. 
     
     
       36. The article of  claim 33  having a porosity of at least 50%. 
     
     
       37. The article of  claim 33  having a porosity of at least 75%. 
     
     
       38. The densified article of  claim 33  having compressive strength of at least about 150 MPa. 
     
     
       39. The densified article of  claim 38 , having a density of at least about 98%. 
     
     
       40. The densified article of  claim 33  having compressive strength of at least about 500 MPa. 
     
     
       41. The densified article of  claim 33  having compressive strength of at least about 700 MPa. 
     
     
       42. The densified article of  claim 38 , having a density of at least about 90%. 
     
     
       43. The densified article of  claim 38 , having a density of at least about 95%. 
     
     
       44. The article of  claim 24  that is a part of a prosthesis. 
     
     
       45. A method for preparing particulate apatite comprising:
 (i) precipitating apatite by adding a calcium source to a phosphate source, wherein the pH of the mixture is about 7 to about 14,   (ii) aging the precipitated apatite,   (iii) controlling the conditions of steps (i) and (ii) so as to produce an apatite precipitate having an average crystal size of 150 nm or less,   (iv) collecting the apatite precipitate, and   (v) drying the apatite precipitate to obtain a particulate apatite having an average crystal size of 150 nm or less, a surface area of at least 40 m 2 /g and particle size of 1 μm or less.   
     
     
       46. The method of claim 45, wherein the calcium source has a concentration of less than about 1 M. 
     
     
       47. The method of claim 46, wherein the calcium source has a concentration of less than about 0.5 M. 
     
     
       48. The method of claim 45, wherein the calcium source is calcium nitrate and the phosphorus source is diammonium hydrogen phosphate. 
     
     
       49. The method of claim 45, wherein the calcium source and phosphate source has an atomic ratio (Ca/P) of about 1.67. 
     
     
       50. The method of claim 45, wherein the calcium source is added to the phosphate source at an addition rate of less than about 0.010 mole per minute. 
     
     
       51. The method of claim 45, wherein the mixture has a pH of between about 11 and about 13. 
     
     
       52. The method of claim 45, wherein the precipitated apatite is aged at a temperature of about −25° C. to about 100° C. 
     
     
       53. The method of claim 52, wherein the precipitated apatite is aged at a temperature of about 20° C. 
     
     
       54. The method of claim 45, wherein the precipitated apatite is aged for at least 12 hours. 
     
     
       55. The method of claim 45, further comprising wet grinding the precipitated apatite. 
     
     
       56. The method of claim 45, wherein the step of precipitating comprises adding an auxiliary structural additive. 
     
     
       57. The method of claim 56, wherein the auxiliary structural additive comprises a ceramic additive. 
     
     
       58. The method of claim 57, wherein the ceramic additive is a metal oxide. 
     
     
       59. The method of claim 56, wherein the auxiliary structural additive is a metal or alloy. 
     
     
       60. The method of claim 45, wherein the step of precipitating comprises adding a carbonate source. 
     
     
       61. A method of producing a densified apatite structure comprising:
 (i) providing particulate apatite having an average particle size of 1 μm or less, an average crystal size of 150 nm or less, and a surface area of at least about 40 m 2 /g, and   (ii) densifying the particulate apatite at a temperature of no more than 1100° C. to produce a densified apatite structure having a dimension of at least about 0.5 cm and an average XRD crystal size of less than 250 nm.   
     
     
       62. The method of claim 61, wherein the particulate apatite is densified by sintering. 
     
     
       63. The method of claim 62, wherein the particulate apatite is densified by pressureless sintering. 
     
     
       64. The method of claim 62, wherein the particulate apatite is densified by hot pressing. 
     
     
       65. The method of claim 61, wherein the particulate apatite is densified at a temperature of no more than 1000° C. 
     
     
       66. The method of claim 61, wherein the densifying step occurs in the absence of sintering aids. 
     
     
       67. The method of claim 61, wherein the method further comprises colloidal pressing. 
     
     
       68. The method of claim 61, further comprising the step of calcining the composition at a temperature of less than about 1000° C. 
     
     
       69. The method of claim 61, wherein the densifying step occurs for a period of time of no more than about 2 hours. 
     
     
       70. The method of claim 61, wherein apatite phase decomposition of less than about 10% occurs. 
     
     
       71. The method of claim 61, wherein the particulate apatite comprises an auxiliary structural additive. 
     
     
       72. The method of claim 61, wherein the particulate apatite comprises carbonate. 
     
     
       73. A method for preparing particulate apatite comprising:
 (i) precipitating apatite by mixing calcium nitrate and diammonium hydrogen phosphate, wherein the pH of the mixture is about 7 to about 14,   (ii) aging the precipitated apatite,   (iii) controlling the conditions of steps (i) and (ii) so as to produce an apatite precipitate having an average crystal size of 150 nm or less,   (iv) collecting the apatite precipitate, and   (v) drying the apatite precipitate to obtain a particulate apatite having an average crystal size of 150 nm or less, a surface area of at least 40 m 2 /g and particle size of 1 μm or less.   
     
     
       74. The method of claim 73, wherein the precipitated apatite is aged at a temperature of about 20° C. 
     
     
       75. The method of claim 73, wherein the precipitated apatite is aged for at least 12 hours. 
     
     
       76. The method of claim 73, further comprising wet grinding the precipitated apatite. 
     
     
       77. A method for preparing particulate apatite comprising:
 (i) precipitating apatite by mixing a calcium source and a phosphate source, wherein the pH of the mixture is about 11 to about 13,   (ii) aging the precipitated apatite,   (iii) controlling the conditions of steps (i) and (ii) so as to produce an apatite precipitate having an average crystal size of 150 nm or less,   (iv) collecting the apatite precipitate, and   (v) drying the apatite precipitate to obtain a particulate apatite having an average crystal size of 150 nm or less, a surface area of at least 40 m 2 /g and particle size of 1 μm or less.   
     
     
       78. The method of claim 77, wherein the precipitated apatite is aged at a temperature of about 20° C. 
     
     
       79. The method of claim 77, wherein the precipitated apatite is aged for at least 12 hours. 
     
     
       80. The method of claim 77, further comprising wet grinding the precipitated apatite.