Composition for an injectable bone mineral substitute material

Abstract

The invention refers to an injectable composition for a bone mineral substitute material, which comprises a dry powder mixed with an aqueous liquid. The powder comprises a first reaction component comprising a calcium suphate hemihydrate with the capability of being hardened to calcium sulphate dihydrate when reacting with said aqueous liquid; a second reaction component, which comprises a calcium phosphate with the capability of being hardened to a calcium phosphate cement when reacting with said aqueous liquid; and at least one accelerator for the reaction of said first and/or second reaction component with said aqueous liquid. A method of producing an injectable bone mineral substitute material is also provided, wherein the composition is mixed in a closed mixing and delivery system for delivery.

1 - 33 . (canceled) 
     
     
         34 . A composition for a bone mineral substitute material comprising
 a dry powder to be mixed with an aqueous liquid, the dry powder comprising a first setting reaction component, which is a calcium sulphate hemihydrate;   a second setting reaction component, which is a calcium phosphate; and   at least one accelerator for the setting reaction of both the first and the second setting reaction components with the aqueous liquid, wherein the at least one accelerator for the reaction of the second component with the aqueous liquid is dissolved in the aqueous liquid.   
     
     
         35 . The composition of  claim 34 , wherein the calcium sulphate hemihydrate is an α-calcium sulphate hemihydrate. 
     
     
         36 . The composition according to  claim 34 , wherein the calcium phosphate is a tricalcium phosphate. 
     
     
         37 . The composition according to  claim 34 , wherein the accelerator is disodium hydrogen phosphate (Na 2 HPO 4 ). 
     
     
         38 . The composition according to  claim 34 , wherein the accelerator comprises 0.1 wt % to 10 wt % of the aqueous liquid. 
     
     
         39 . The composition according to  claim 38 , wherein the accelerator comprises 1 wt % to 5 wt % of the aqueous liquid. 
     
     
         40 . The composition according to  claim 34 , wherein the aqueous liquid comprises distilled water or a balanced salt solution. 
     
     
         41 . The composition of  claim 34 , wherein the aqueous liquid comprises between 0.1 ml and 2 ml per gram of the powder. 
     
     
         42 . The composition of  claim 41 , wherein the aqueous liquid comprises between 0.5 ml and 1 ml per gram of the powder. 
     
     
         43 . The composition of  claim 34  further comprising a biologically active substance. 
     
     
         44 . The composition of  claim 43 , wherein the biologically active substance is chosen from a growth factor, an anti-cancer substance, an antibiotic, and an antioxidant, and mixtures thereof. 
     
     
         45 . A composition for a bone mineral substitute material comprising
 a dry powder to be mixed with an aqueous liquid, the dry powder comprising a first setting reaction component, which is a calcium sulphate hemihydrate;   a second setting reaction component, which is a calcium phosphate;   at least one accelerator for the setting reaction of the first or the second setting reaction component, or both the first and the second setting reaction components with the aqueous liquid, wherein the at least one accelerator for the reaction of the second component with the aqueous liquid is dissolved in the aqueous liquid, and   a biologically compatible oil to improve the injectability of the composition.   
     
     
         46 . The composition of  claim 45 , wherein the calcium sulphate hemihydrate is an α-calcium sulphate hemihydrate. 
     
     
         47 . The composition according to  claim 45 , wherein the calcium phosphate is a tricalcium phosphate. 
     
     
         48 . The composition according to  claim 45 , wherein the biologically compatible oil is vitamin E. 
     
     
         49 . The composition according to  claim 45 , wherein the biologically compatible oil comprises 0.1 wt % to 5 wt % of the composition. 
     
     
         50 . The composition according to  claim 49 , wherein the biologically compatible oil comprises 0.5 wt % to 2 wt % of the composition. 
     
     
         51 . A composition for a bone mineral substitute material comprising
 a dry powder to be mixed with an aqueous liquid, the dry powder comprising a first setting reaction component, which is a calcium sulphate hemihydrate;   a second setting reaction component, which is a calcium phosphate;   at least one accelerator for the setting reaction of the first or the second setting reaction component, or both the first and the second setting reaction components with the aqueous liquid, wherein the at least one accelerator for the reaction of the second component with the aqueous liquid is dissolved in the aqueous liquid; and   a pH reducing component in order to improve the injectability of the composition.   
     
     
         52 . The composition of  claim 51 , wherein the calcium sulphate hemihydrate is an α-calcium sulphate hemihydrate. 
     
     
         53 . The composition of  claim 51 , wherein the calcium phosphate is a tricalcium phosphate. 
     
     
         54 . The composition of  claim 51 , wherein the pH reducing component is ascorbic acid or citric acid. 
     
     
         55 . The composition of  claim 51 , wherein the pH reducing component comprises 0.1 wt % to 5 wt %. 
     
     
         56 . The composition of  claim 55 , wherein the pH reducing component comprises 0.5 wt % to 2 wt % of the composition. 
     
     
         57 . A method of producing an injectable bone mineral substitute material, wherein the composition of  claim 34  is mixed with the aqueous liquid in a closed mixing and delivery system. 
     
     
         58 . The method of  claim 57 , wherein the mixing is conducted under conditions of subatmospheric pressure. 
     
     
         59 . A method of producing an injectable bone mineral substitute material, wherein the composition of  claim 51  is mixed with the aqueous liquid in a closed mixing and delivery system. 
     
     
         60 . The method of  claim 59 , wherein the mixing is conducted under conditions of subatmospheric pressure. 
     
     
         61 . A method of producing a composition for bone mineral substitute material, comprising contacting the composition of  claim 34  with an aqueous liquid. 
     
     
         62 . The method of  claim 61 , wherein the composition is capable of being hardened in a body fluid in vivo to a bi-phasic cement implant that with time obtains a porous structure for bone ingrowth. 
     
     
         63 . A kit for use in preparing a composition for a bone mineral substitute material, said kit comprising:
 (1) the composition according to  claim 34 ; and   (2) optionally an aqueous liquid.