Self-setting calcium phosphate pastes and related products

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 formable paste, suitable for use as a bone substitution material, comprising: 
 a reactive amorphous calcium phosphate material having at least 90% amorphous character and characterized in that, when prepared 1:1 as a mixture with dicalcium phosphate dihydrate (DCPD) in water, wherein at least 20% by weight of said DCPD is retained by a 106μ sieve, the mixture remains injectable and formable for a time greater than about 60 minutes at about 18-19° C. and hardens at about 37° C. within about 10 to 60 minutes;    a second calcium phosphate; and    an aqueous-based fluid in an amount to provide a paste having a formable or injectable consistency at a temperature of about 18-19° C.    
     
     
         2 . The paste of  claim 1 , wherein said amorphous calcium phosphate has a Ca/P molar ratio of about 1.1 to 1.65.  
     
     
         3 . The paste of  claim 1 , wherein said second calcium phosphate has a Ca/P molar ration of less than or equal to 1.67.  
     
     
         4 . The paste of  claim 1 ,  2 , or  3 , further comprising a supplementary material selected to change a physical parameter of the paste or the hardened product, said parameter selected from the group consisting of strength, resorption time, adherence, injectability, frictional characteristics, release kinetics, tensile strength, hardness, fracture toughness, elasticity, imaging capability, flow properties and setting times.  
     
     
         5 . The paste of  claim 1 , further comprising a therapeutic substance.  
     
     
         6 . The paste of  claim 1 , wherein the fluid is selected from the group consisting of water, saline, non-phosphate buffer solutions, serum and tissue culture medium.  
     
     
         7 . The paste of  claim 5 , wherein said therapeutic substance is selected from the group consisting of growth factors, antibiotics, anti-cancer agents, and analgesics.  
     
     
         8 . The paste of  claim 1 , further comprising a crystallization inhibitor selected from the group consisting of carbonates, pyrophosphate, and magnesium.