Calcium phosphate bone cements

Abstract

In a first aspect, the present invention discloses a self setting calcium phosphate cement comprising:—(i) a powdered component, said powdered component having an average particle size d 50 of less than 15 μm, and (ii) a calcium phosphate based powder, said powder having an average particle size d 50 greater than that of the powdered component, said powdered component and said calcium phosphate based powder being suspended in water containing a dissolved zeta potential increasing additive in sufficient quantity to increase the zeta potential of the suspended particles to at least 30 mV, and wherein the zeta potential increasing additive is chosen to be compatible with the setting pH of the same calcium phosphate cement without the zeta potential increasing additive. In a second aspect, the invention discloses a shelf-stable acidic setting cement powder comprising:—(i) a calcium phosphate based powder, and (ii) a powdered compound which, upon addition of water to form a cement paste, retards the cement setting reaction or increases the zeta potential of the resultant suspended particles to at least −30 mV.

The invention claimed is: 
     
       1. A self setting calcium phosphate cement comprising:
 (i) a powdered component selected from the group consisting of:
 (a) calcium phosphate, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, α-tricalcium phosphate, tetracalcium phosphate, hydroxyapatite, octacalcium phosphate, substituted forms thereof, or mixtures thereof; 
 (b) a carbonate, silicate, nitrate, oxide, sulphate or salt of calcium, zirconium, aluminium, titanium or silicon, or mixtures thereof; and 
 (c) mixtures of (a) and (b), 
 said powdered component having an average particle size d 50  of less than 15 μm, and 
   (ii) a calcium phosphate based powder selected from the group consisting of tetracalcium phosphate, α-tricalcium phosphate, hydroxyapatite, monocalcium phosphate monohydrate, monocalcium phosphate anhydrous and mixtures thereof, said powder having an average particle size d 50  greater than that of the powdered component,   said powdered component and said calcium phosphate based powder being suspended in water containing a dissolved zeta potential increasing additive in an amount of from 0.1 to 2 Mol per liter of water and in sufficient quantity to increase the zeta potential of the suspended particles to at least −30 mV, and wherein the zeta potential increasing additive is chosen to be compatible with the setting pH of the same calcium phosphate cement without the zeta potential increasing additive.   
     
     
       2. A cement as claimed in  claim 1 , wherein the d 50  of the calcium phosphate based powder is from 1.5 to 10 times greater than the d 50  of the powdered component. 
     
     
       3. A cement as claimed in  claim 1 , wherein the zeta potential increasing additive is an oligocarboxylic acid compound selected from the group consisting of a group I meat salt, a group II metal salt, an ammonium salt, and a mixed salt. 
     
     
       4. A cement as claimed in  claim 3 , wherein the oligocarboxylic acid compound has two or three carboxyl groups. 
     
     
       5. A cement as claimed in  claim 3  wherein the oligocarboxylic acid compound has one or more hydroxyl groups. 
     
     
       6. A cement as claimed in  claim 3  wherein the oligocarboxylic acid compound is a salt of citric acid, tartaric acid or malic acid. 
     
     
       7. A cement as claimed in  claim 6  wherein said salt is trisodium citrate, disodium malate or disodium tartrate. 
     
     
       8. A cement as claimed in  claim 1 , wherein the zeta potential increasing additive is in sufficient quantity to increase the zeta potential of the calcium phosphate particles to at least −40 and preferably at least −50 mV. 
     
     
       9. A cement as claimed in  claim 1 , wherein the zeta potential increasing additive is present in an amount of from 0.2 to 1 M per liter. 
     
     
       10. A cement as claimed in  claim 1 , wherein the powdered component has a d 50  of no more than 10 μm. 
     
     
       11. A cement as claimed in  claim 1 , wherein the calcium phosphate based powder has a d 50  of at least 3 μm. 
     
     
       12. A cement as claimed in  claim 1 , wherein the calcium phosphate based powder is mechanically activated. 
     
     
       13. A cement as claimed in  claim 1 , wherein the volume ratio of the calcium phosphate based powder to the powdered component is in the range of from 50:50 to 95:5. 
     
     
       14. A cement as claimed in  claim 1 , wherein the powdered component constitutes no more than 40% by volume of the calcium phosphate based powder. 
     
     
       15. A cement as claimed in  claim 14 , wherein the powdered component constitutes no more than 30% by volume of the calcium phosphate based powder. 
     
     
       16. A cement as claimed in  claim 15 , wherein the powdered component constitutes from 10 to 25% by volume of the calcium phosphate based powder. 
     
     
       17. A self setting calcium phosphate cement comprising:
 (i) a powdered component, said powdered component having an average particle size d 50  of less than 15 μm, and   (ii) a calcium phosphate based powder, said powder having an average particle size d 50  greater than that of the powdered component,   said powdered component and said calcium phosphate based powder being suspended in water containing a dissolved zeta potential increasing additive in an amount of from 0.1 to 2 Mol per liter of water and in sufficient quantity to increase the zeta potential of the suspended particles to at least −30 mV, and wherein the zeta potential increasing additive is chosen to be compatible with the setting pH of the same calcium phosphate cement without the zeta potential increasing additive and wherein neither said powdered component nor said calcium phosphate based powder is β-tricalcium phosphate.   
     
     
       18. A self setting calcium phosphate cement comprising:
 (i) a powdered component selected from the group consisting of:
 (a) calcium phosphate, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, α-tricalcium phosphate, tetracalcium phosphate, hydroxyapatite, octacalcium phosphates, substituted forms thereof, or mixtures thereof; 
 (b) a carbonate, silicate, nitrate, oxides, sulphate or salt of calcium, zirconium, aluminium, titanium or silicon, or mixtures thereof; and 
 (c)mixtures of (a) and (b), 
 said powdered component having an average particle size d 50  of less than 15 μm, and 
   (ii) a calcium phosphate based powder selected from the group consisting of tetracalcium phosphate, α-tricalcium phosphate, hydroxyapatite, monocalcium phosphate monohydrate, monocalcium phosphate anhydrous and mixtures thereof, said powder having an average particle size d 50  greater than that of the powdered component,   said powdered component and said calcium phosphate based powder being suspended in water containing a dissolved zeta potential increasing additive in an amount of from 0.1 to 2 Mol per liter of water and in sufficient quantity to increase the zeta potential of the suspended particles to at least −30 mV, and wherein the zeta potential increasing additive is an oligocarboxylic acid compound selected from the group consisting of a group I or group II metal salt, an ammonium salt or a mixed salt.   
     
     
       19. A cement as claimed in  claim 10 , wherein the powdered component has a d 50  of no more than 5 μm. 
     
     
       20. A self-setting calcium phosphate cement comprising (a) a powdered component selected from the group consisting of tetracalcium phosphate, hydroxyapatite and α-tricalcium phosphate, said powdered component having an average particle size d 50  of less than 15 μm; (b) a calcium phosphate based powder selected from the group consisting of tetracalcium phosphate, hydroxyapatite, and α-tricalcium phosphate, said powder having average particle size d 50  greater than that of the powdered component; (c) sodium citrate; and (d) a liquid component,
 Wherein when either the powdered component or the calcium phosphate based component is suspended in water containing sodium citrate at a concentration of 0.05 Mol per liter, the zeta potential of the suspended particles is at least −30 mV.