Methods and products related to the physical conversion of reactive amorphous calcium phosphate

Abstract

The present invention provides a novel process for producing a calcium phosphate cement or filler which hardens in a temperature dependent fashion in association with an endothermic reaction. In the reaction a limited amount of water is mixed with dry calcium phosphate precursors to produce a hydrated precursor paste. Hardening of the paste occurs rapidly at body temperature an is accompanied by the conversion of one or more of the reactants to poorly crystalline apatitic calcium phosphate. The hardened cements, fillers, growth matrices, orthopedic and delivery devices of the invention are rapidly resorbable and stimulate hard tissue growth and healing.

What is claimed is:  
     
         1 . A calcium phosphate cement composition, comprising: 
 an amorphous calcium phosphate having a calcium to phosphate molar ration of about 1.55 to 1.65;    at least one additional calcium phosphate source; and    a physiologically acceptable aqueous liquid.    
     
     
         2 . The calcium phosphate cement composition of  claim 1 , wherein said at least one additional calcium source is a calcium source selected from the group consisting of calcium oxide, calcium hydroxide, calcium carbonate, and calcium phosphate.  
     
     
         3 . The calcium phosphate cement composition of  claim 2 , wherein said calcium phosphate of said at least one additional calcium source is selected from the group consisting of tetracalcium phosphate, tricalcium phosphate and monocalcium phosophate monohydrate.  
     
     
         4 . The calcium phosphate cement composition of  claim 2 , wherein said amorphous calcium phosphate is a solid.  
     
     
         5 . The calcium phosphate cement composition of  claim 2 , wherein said amorphous calcium phosphate is a gel.  
     
     
         6 . The calcium phosphate cement composition of  claim 5 , wherein said gel consists of said amorphous calcium phosphate and said physiologically acceptable liquid.  
     
     
         7 . A calcium phosphate composition comprising: 
 a dry component comprising an amorphous calcium phosphate having a calcium to phosphate molar ration of about 1.55 to 1.65 and at least one additional calcium phosphate; and    a physiologically acceptable aqueous lubricant.    
     
     
         8 . The calcium phosphate composition of  claim 7 , wherein said at least one additional calcium phosphate is selected from the group consisting of tetracalcium phosphate, tricalcium phosphate and monocalcium phosphate monohydrate.  
     
     
         9 . The calcium phosphate composition of  claim 8 , wherein said cement further comprises an organic polymer.  
     
     
         10 . The calcium phosphate composition of  claim 9 , wherein said organic polymer is a protein.  
     
     
         11 . A method for preparing a remodelable calcium phosphate mineral, said method comprising: 
 combining an amorphous calcium phosphate having a calcium to phosphate molar ratio of about 1.55 to 1.65; at least one additional calcium source; and a physiologically acceptable aqueous liquid to produce a flowable composition; and    allowing said flowable composition to set into said calcium phosphate mineral.    
     
     
         12 . The method of  claim 11 , wherein sad at least one additional calcium source is a calcium source selected from the group consisting of calcium oxide, calcium hydroxide, calcium carbonate, and calcium phosphate.  
     
     
         13 . The method of  claim 11 , wherein said at least one additional calcium phosphate is selected from the group consisting of tetracalcium phosphate, tricalcium phosphate and monocalcium phosphate monohydrate.  
     
     
         14 . The method of  claim 12 , wherein said calcium phosphate is an apatite.  
     
     
         15 . The method of  claim 14 , wherein said apatite is hydroxyapatite.  
     
     
         16 . The method of  claim 15 , wherein said hydroxyapatite is a calcium deficient calcium phosphate.  
     
     
         17 . A method for preparing a remodelable hydroxyapatite, said method comprising: 
 combining an amorphous calcium phosphate having a calcium to phosphate molar ratio of about 1.55 to 1.65; at least one additional calcium phosphate source; and a physiologically acceptable aqueous liquid to produce a flowable composition; and    allowing said flowable composition to set into said remodelable hydroxyapatite.    
     
     
         18 . The method of  claim 17 , wherein said remodelable hydroxyapatite is calcium deficient hydroxyapatite.  
     
     
         19 . The method of  claim 17 , wherein said at least one additional calcium phosphate is tetracalcium phosphate.  
     
     
         20 . The method of  claim 17 , wherein said at least one additional calcium phosphate is tricalcium phosphate.