Calcium phosphate bone substitute materials

Claim 1

A uniform calcium phosphate-containing material useful as bone substitute material or for the manufacture of prosthetic devices, having a cancellous structure characteristic of boney tissue or bone or a substantially uniformly permeable microporous structure characterized by a substantially uniform pore volume in the range from about 10 to about 90% and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous carbonate echinoderm or scleractinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said material into two interpenetrating regions, each of which is a single multiple connected domain, said material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said material comprising a calcium phosphate having a calcium to phosphorus Ca/P atomic ratio in the range 1.0-2.0 and consisting essentially of a mixture of dicalcium phosphate Ca 2 P 2 O 7 and tricalcium phosphate Ca 3 P 2 O 8 or a mixture of tricalcium phosphate Ca 3 P 2 O 8 and hydroxyapatite or a mixture of tetracalcium phosphate Ca 4 P 2 O 9 and hydroxyapatite.

Claim 31

A method of converting calcium hydroxyapatite material having a calcium to phosphorus Ca/P atomic ratio of 1.66 to a uniform calcium phosphate material useful as bone substitute material or for the manufacture of prosthetic devices, said hydroxyapatite material having a substantially uniformly permeable microporous structure characterized by a substantially uniform pore volume in the range from about 10 to about 90% and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous carbonate echinoderm or scleractinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said hydroxyapatite material into two interpenetrating regions, each of which is a single multiple connected domain, said hydroxyapatite material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio lower than 1.66 and consisting essentially of a mixture of dicalcium phosphate Ca 2 P 2 O 7 and tricalcium phosphate Ca 3 P 2 O 8 which comprises contacting said hydroxyapatite material with a phosphate solution to effect substantially uniform wetting of said hydroxyapatite material by said phosphate solution, drying the resulting treated hydroxyapatite material to effect deposition of the phosphate from said solution substantially uniformly onto the surface of said hydroxyapatite material and heating or firing the resulting phosphate treated hydroxyapatite material to decrease the calcium to phosphorus Ca/P atomic ratio thereof to a value less than 1.66 to produce a calcium phosphate material consisting essentially of a mixture of dicalcium phosphate Ca 2 P 2 O 7 and tricalcium Ca 3 P 2 O 8 or a mixture of dicalcium phosphate Ca 2 P 2 O 7 tricalcium phosphate Ca 3 F2O 8 and hydroxyapatite.

Claim 32

A method of converting calcium hydroxyapatite material having a calcium to phosphorus Ca/P atomic ratio of 1.66 to a uniform calcium phosphate material useful as bone substitute material or for the manufacture of prosthetic devices, said hydroxyapatite material having a substantially uniformly permeable microporous structure characterized by a substantially uniform pore volume in the range from about 10 to about 90% and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous carbonate echinoderm or scleractinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said hydroxyapatite material into two interpenetrating regions, each of which is a single multiple connected domain, said hydroxyapatite material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio lower than 1.66 and consisting essentially of a mixture of dicalcium phosphate Ca 2 P 2 O 7 and tricalcium phosphate Ca 3 P 2 O 8 which comprises contacting said hydroxyapatite material with a phosphate solution to effect substantially uniform wetting of said hydroxyapatite material by said phosphate solution, drying the resulting treated hydroxyapatite material to effect deposition of the phosphate from said solution substantially uniformly onto the surface of said hydroxyapatite material and heating or firing the resulting phosphate treated hydroxyapatite material to decrease the calcium to phosphorus Ca/P atomic ratio thereof to a value less than 1.66 to produce a calcium phosphate material consisting essentially of a mixture of dicalcium phosphate Ca 2 P 2 O 7 and tricalcium Ca 3 P 2 O 8 or a mixture of dicalcium phosphate Ca 2 P 2 O 7 tricalcium phosphate Ca 3 F2O 8 and hydroxyapatite.

Claim 39

A method of converting calcium hydroxyapatite material having a calcium to phosphorus Ca/P atomic ratio of 1.66 to a uniform phosphate material useful as bone substitute material or for the manufacture of prosthetic devices, said hydroxyapatite material having a substantially uniformly permeable microporous structure characterized by a substantially uniform pore volume in the range from about 10 to about 90% and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous carbonate echinoderm or scleractinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said hydroxyapatite material into two interpenetrating regions, each of which is a single multiple connected domain, said hydroxyapatite material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio greater than 1.66 and up to 2.0 and containing tetracalcium phosphate Ca 4 P 2 O 9 which comprises contacting said hydroxyapatite material with a calcium-containing solution to effect substantially uniform absorption or wetting of said calcium-containing solution by said hydroxyapatite material or substantially uniform wetting of said hydroxyapatite material by said calcium-containing solution, drying the resulting treated hydroxyapatite material to effect deposition of the calcium-containing component of said solution substantially uniformly onto the surface of said hydroxyapatite material and heating or firing the resulting calcium treated hydroxyapatite material to increase the Calcium to phosphorus Ca/P atomic ratio thereof to a value greater than 1.66 and up to 2.0 and to produce a calcium phosphate material consisting essentially of a mixture of hydroxyapatite and tetracalcium phosphate Ca 4 P 2 O 9 .

Claim 40

A method of converting calcium hydroxyapatite material having a calcium to phosphorus Ca/P atomic ratio of 1.66 to a uniform phosphate material useful as bone substitute material or for the manufacture of prosthetic devices, said hydroxyapatite material having a substantially uniformly permeable microporous structure characterized by a substantially uniform pore volume in the range from about 10 to about 90% and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous carbonate echinoderm or scleractinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said hydroxyapatite material into two interpenetrating regions, each of which is a single multiple connected domain, said hydroxyapatite material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio greater than 1.66 and up to 2.0 and containing tetracalcium phosphate Ca 4 P 2 O 9 which comprises contacting said hydroxyapatite material with a calcium-containing solution to effect substantially uniform absorption or wetting of said calcium-containing solution by said hydroxyapatite material or substantially uniform wetting of said hydroxyapatite material by said calcium-containing solution, drying the resulting treated hydroxyapatite material to effect deposition of the calcium-containing component of said solution substantially uniformly onto the surface of said hydroxyapatite material and heating or firing the resulting calcium treated hydroxyapatite material to increase the Calcium to phosphorus Ca/P atomic ratio thereof to a value greater than 1.66 and up to 2.0 and to produce a calcium phosphate material consisting essentially of a mixture of hydroxyapatite and tetracalcium phosphate Ca 4 P 2 O 9 .

Claim 47

A method of converting calcium hydroxyapatite material having a calcium to phosphorus Ca/P atomic ratio of 1.66 to a uniform calcium phosphate material useful as bone substitute material or of the manufacture of prosthetic devices, said hydroxyapatite material having a substantially uniformly permeable microporous structure characterized by a substantially uniform pore volume in the rang e from about 10 to about 90% and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous carbonate echinoderm or scleractinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said hydroxyapatite material into two interpenetrating regions, each of which is a single multiple connected domain, said hydroxyapatite material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio lower than 1.66 and consisting essentially of a mixture of dicalcium phosphate Ca 2 P 2 O 7 and tricalcium phosphate Ca 3 P 2 O 8 or a mixture of tricalcium phosphate and hydroxapatite or said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio greater than 1.66 and containing hydroxyapatite and tetracalcium phosphate Ca 4 P 2 O 9 which comprises contacting said hydroxyapatite material with a phosphate solution or with a calcium-containing solution to effect substantially uniform absorption of said phosphate solution or said calcium-containing solution by said hydroxyapatite material or substantially uniform wetting of said hydroxyapatite material by said phosphate solution or said calcium-containing solution, drying the resulting treated hydroxyapatite material to effect deposition of the phosphate from said phosphate solution or the calcium from said calcium-containing solution onto the surface of said hydroxyapatite material and heating or firing the resulting treated hydroxapatite material to decrease the calcium to phosphorus Ca/P atomic ratio thereof to a value less than 1.66 and in the range 1.0-1.5 and to produce a calcium phosphate material consisting essentially of a mixture of dicalcium phosphate Ca 2 P 2 O 7 and tricalcium phosphate Ca 3 P 2 O 8 when the solution applied to said hydroxyapatite material is said phosphate solution and to produce a calcium phosphate material having a calcium to phosphate Ca/P atomic ratio greater than 1.66 and up to 2.0 and consisting essentially of hydroxyapatite and tetracalcium phosphate Ca 4 P 2 O 9 when said solution is a calcium-containing solution.

Claim 48

A method of converting calcium hydroxyapatite material having a calcium to phosphorus Ca/P atomic ratio of 1.66 to a uniform calcium phosphate material useful as bone substitute material or of the manufacture of prosthetic devices, said hydroxyapatite material having a substantially uniformly permeable microporous structure characterized by a substantially uniform pore volume in the rang e from about 10 to about 90% and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous carbonate echinoderm or scleractinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said hydroxyapatite material into two interpenetrating regions, each of which is a single multiple connected domain, said hydroxyapatite material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio lower than 1.66 and consisting essentially of a mixture of dicalcium phosphate Ca 2 P 2 O 7 and tricalcium phosphate Ca 3 P 2 O 8 or a mixture of tricalcium phosphate and hydroxapatite or said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio greater than 1.66 and containing hydroxyapatite and tetracalcium phosphate Ca 4 P 2 O 9 which comprises contacting said hydroxyapatite material with a phosphate solution or with a calcium-containing solution to effect substantially uniform absorption of said phosphate solution or said calcium-containing solution by said hydroxyapatite material or substantially uniform wetting of said hydroxyapatite material by said phosphate solution or said calcium-containing solution, drying the resulting treated hydroxyapatite material to effect deposition of the phosphate from said phosphate solution or the calcium from said calcium-containing solution onto the surface of said hydroxyapatite material and heating or firing the resulting treated hydroxapatite material to decrease the calcium to phosphorus Ca/P atomic ratio thereof to a value less than 1.66 and in the range 1.0-1.5 and to produce a calcium phosphate material consisting essentially of a mixture of dicalcium phosphate Ca 2 P 2 O 7 and tricalcium phosphate Ca 3 P 2 O 8 when the solution applied to said hydroxyapatite material is said phosphate solution and to produce a calcium phosphate material having a calcium to phosphate Ca/P atomic ratio greater than 1.66 and up to 2.0 and consisting essentially of hydroxyapatite and tetracalcium phosphate Ca 4 P 2 O 9 when said solution is a calcium-containing solution.

Claim 49

A method of treating calcium phosphate material, said calcium phosphate material having a substantially uniform permeable microporous structure characterized by a substantially uniform pore volume in the rang from about 10 to about 90% and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous echinoderm or scleractinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said calcium phosphate material into two interpenetrating regions, each of which is a single multiple-connected domain, said calcium phosphate material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio in the range 1.0 to 2.0 to change the Ca/P ratio to a higher value in the range 1.0-2.0 which comprises, wherein the Ca/P ratio of said calcium phosphate material is 1.0 or greater but less than 2, adding or incorporating a solution of a calcium-contributing moiety to said calcium phosphate material and firing the resulting treated calcium phosphate material to yield a fired uniform calcium phosphate produce which has a calcium to phosphate atomic ratio greater than the Ca/P ratio of said calcium phosphate material.

Claim 50

A method of treating calcium phosphate material, said calcium phosphate material having a substantially uniform permeable microporous structure characterized by a substantially uniform pore volume in the rang from about 10 to about 90% and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous echinoderm or scleractinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said calcium phosphate material into two interpenetrating regions, each of which is a single multiple-connected domain, said calcium phosphate material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having a calcium to phosphorus Ca/P atomic ratio in the range 1.0 to 2.0 to change the Ca/P ratio to a higher value in the range 1.0-2.0 which comprises, wherein the Ca/P ratio of said calcium phosphate material is 1.0 or greater but less than 2, adding or incorporating a solution of a calcium-contributing moiety to said calcium phosphate material and firing the resulting treated calcium phosphate material to yield a fired uniform calcium phosphate produce which has a calcium to phosphate atomic ratio greater than the Ca/P ratio of said calcium phosphate material.

Claim 51

A method of treating a calcium phosphate material wherein said calcium phosphate material has a substantially uniformly permeable microporous structure characterized by a substantially uniform pore volume in the range from about 10 to about 90$ and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous echinoderm or sceleratinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said calcium phosphate material into tow interpenetrating regions, each of which is a single multiple-connected domain, said calcium phosphate material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having calcium to phosphate Ca/P atomic ratio in the range 1.0 to 2.0 to change the Ca/P ratio to a lower value in the range 1.0-2.0, which comprises, where the Ca/P ratio of said calcium phosphate material is 2.0 or less but greater than 1, adding or incorporating a phosphate-contributing or phosphorus-contributing moiety to said calcium phosphate material and firing the resulting treated calcium phosphate material to yield a fired uniform calcium phosphorus product which has a calcium to phosphate atomic ratio less than the Ca/P ratio of said calcium phosphate material.

Claim 52

A method of treating a calcium phosphate material wherein said calcium phosphate material has a substantially uniformly permeable microporous structure characterized by a substantially uniform pore volume in the range from about 10 to about 90$ and by a pronounced three-dimensional fenestrate structure corresponding to the microstructure of the porous echinoderm or sceleratinian coral skeletal material of marine life and providing a periodic minimal surface, said periodic minimal surface dividing the volume of said calcium phosphate material into tow interpenetrating regions, each of which is a single multiple-connected domain, said calcium phosphate material having a substantially uniform pore size diameter and substantially uniform pore connections or openings in the range from about 5 microns to about 500 microns, said calcium phosphate material having calcium to phosphate Ca/P atomic ratio in the range 1.0 to 2.0 to change the Ca/P ratio to a lower value in the range 1.0-2.0, which comprises, where the Ca/P ratio of said calcium phosphate material is 2.0 or less but greater than 1, adding or incorporating a phosphate-contributing or phosphorus-contributing moiety to said calcium phosphate material and firing the resulting treated calcium phosphate material to yield a fired uniform calcium phosphorus product which has a calcium to phosphate atomic ratio less than the Ca/P ratio of said calcium phosphate material.