Method for producing porous calcium deficient hydroxyapatite granules

1. Porous calcium deficient hydroxyapatite granules made by a process comprising the following steps:

(a) obtaining porous granules of CSA, CSH, or CSD by sintering CSA, CSH, or CSD powder at 650° C. to 1100° C., mixing the CSA, CSH, or CSD powder with an aqueous or non-aqueous solution to form a slurry, solidifying the slurry, breaking the resulting block into granules, and then sintering the obtained granules at a temperature between 650° C. to 1100° C.;

(b) subjecting granules of calcium sulfate anhydrous (CSA), calcium sulfate dihydrate (CSD) or calcium sulfate hemihydrate (CSH), the granules comprising interconnected pores with a minimum mean diameter of 3 microns, to a first incubation in an alkaline aqueous solution having a pH-value of less than 10 and containing PO 4 3− ions for 1.5 hours to 5 days, forming the alkaline aqueous solution for the first incubation by a mixture of (NH 4 ) 2 HPO 4 and NaOH;

(c) subjecting the granules of step (a) to a second incubation for up to 2 days in an alkaline aqueous solution having a pH sufficient to increase the residual pH value of the granules, said alkaline aqueous solution optionally comprising PO 4 3− ions, forming the alkaline aqueous solution for the second incubation by a mixture of (NH 4 ) 2 HPO 4 and NaOH or only NaOH, and performing the first incubation and/or the second incubation at a temperature of 60° C. to 100° C.;

(d) filtering and drying the obtained porous granules of calcium deficient hydroxyapatite;

wherein the sum of the amounts of PO 4 3− ions present in the first and second incubation is at least as large as the amount of SO 4 2− ions of the granules used for step (a); and

wherein the porous calcium deficient hydroxyapatite granules have a composition corresponding to Ca (10−x) (PO 4 ) (6−x) (HPO 4 ) x (OH) (2−x) where 0<x<2; and wherein the porous calcium deficient hydroxyapatite granules have a Ca:P ratio in the range of 1.51 to 1.59.

2. The porous calcium deficient hydroxyapatite granules according to claim 1 , wherein said granules

1) comprise a plurality of micropores with a minimum mean diameter of 3 microns; and

2) the micropores have a mean diameter of less than 20 microns.

3. The porous calcium deficient hydroxyapatite granules according to claim 1 , wherein the porous calcium deficient hydroxyapatite granules have a specific surface area (SSA) higher than 30 m 2 /g.

4. The porous calcium deficient hydroxyapatite granules according to claim 1 , wherein the porous calcium deficient hydroxyapatite granules have a SSA higher than 50 m 2 /g.

5. The porous calcium deficient hydroxyapatite granules according to claim 1 , wherein the porous calcium deficient hydroxyapatite granules have a specific surface area (SSA) lower than 120 m 2 /g.

6. The porous calcium deficient hydroxyapatite granules of claim 1 , wherein the drying comprises a spray drying process.

7. The porous calcium deficient hydroxyapatite granules of claim 6 , wherein the spray drying process is controlled so as to produce spherical porous calcium deficient hydroxyapatite granules with a mean diameter below 200 μm.

8. The porous calcium deficient hydroxyapatite granules according to step (a) of claim 1 , wherein the CSA, CSD or CSH porous granules are shaped with a high shear mixer and calcined.

9. The porous calcium deficient hydroxyapatite granules made according to claim 1 , wherein the CDHA granules are larger than 50 micrometers in diameter.

10. The porous calcium deficient hydroxyapatite granules made according to claim 1 , wherein the CDHA granules are smaller than 3000 micrometers in diameter.

11. The porous calcium deficient hydroxyapatite granules made according to claim 1 , wherein the granules of calcium sulfate anhydrous (CSA), calcium sulfate dihydrate (CSD) or calcium sulfate hemihydrate (CSH) used in step (a) comprise less than 1 weight-% of carbon residues.

12. The porous calcium deficient hydroxyapatite granules of claim 1 , wherein the first and/or the second incubation comprises stirring the CSA, CSH, or CSD granules in a solution.

13. A process comprising the following steps:

(a) obtaining porous granules of CSA, CSH, or CSD by sintering CSA, CSH, or CSD powder at 650° C. to 1100° C., mixing the CSA, CSH, or CSD powder with an aqueous or non-aqueous solution to form a slurry, solidifying the slurry, breaking the resulting block into granules, and then sintering the obtained granules at a temperature between 650° C. to 1100° C.;

(b) subjecting granules of calcium sulfate anhydrous (CSA), calcium sulfate dihydrate (CSD) or calcium sulfate hemihydrate (CSH), the granules comprising interconnected pores with a minimum mean diameter of 3 microns, to a first incubation in an alkaline aqueous solution having a pH-value of less than 10 and containing PO 4 3− ions for 1.5 hours to 5 days, forming the alkaline aqueous solution for the first incubation by a mixture of (NH 4 ) 2 HPO 4 and NaOH;

(c) subjecting the granules of step (a) to a second incubation for 0.5 hours to 2 days in an alkaline aqueous solution having a pH sufficient to increase the residual pH value of the granules, said alkaline aqueous solution optionally comprising PO 4 3− ions, forming the alkaline aqueous solution for the second incubation by a mixture of (NH 4 ) 2 HPO 4 and NaOH or only NaOH, and performing the first incubation and/or the second incubation at a temperature of 60° C. to 100° C.; and

(d) filtering and drying the obtained porous granules of calcium deficient hydroxyapatite; wherein the sum of the amounts of PO 4 3− ions present in the first and second incubation is at least as large as the amount of SO 4 2− ions of the granules used for step (a); wherein the porous calcium deficient hydroxyapatite granules have a composition corresponding to Ca (10−x) (PO 4 ) (6−x) (HPO 4 ) x (OH) (2−x) where 0<x<2; and wherein the porous calcium deficient hydroxyapatite granules have a Ca:P ratio in the range of 1.51 to 1.59.