Hydraulic cement-based implant material and use thereof

Abstract

The invention relates to implant materials that are based on hydraulic cements in the form of one or more pastes, suspensions or dispersions that contain mineral and/or organic and/or organomineral solids and that react, when combined or when reacted with an aqueous liquid, to a solid in a cement-type initiation reaction. The invention also relates to the use of these materials as technical, medical-technical and/or pharmaceutical products, especially as bone cements, bone replacement materials, bone glues, dental filling materials and implantable active ingredient carriers. The implant materials according to the invention in the form of one or more pastes, suspensions or dispersions that contain mineral and/or organic and/or organomineral solids are formulated in an excipient liquid in such a manner that the pastes, suspensions or dispersions are stable in storage at normal conditions over a prolonged period of time and that they react, when combined with an aqueous liquid or when added to an aqueous liquid, in a cement-type initiation reaction and set to a solid. The excipient liquid of the mineral paste, suspension or dispersion is substantially water-free, and water immiscible or insoluble or hardly soluble in water in the chemical sense.

1 . Implant material on the basis of a hydraulic cement of at least one component in the form of a paste, suspension or dispersion, containing at least one powdery solid containing calcium and/or magnesium compounds, that, upon mixing with an aqueous liquid or after introduction into an aqueous liquid, cures to a solid body, wherein the at least one component contains a solid and a carrier liquid that is substantially free of water and in the chemical sense is not miscible with water, and wherein the paste, suspension or dispersion under normal conditions does not surpass the consistency of a kneedable mass. 
     
     
         2 . Implant material according to  claim 1 , characterized in that the solids are suspended/dispersed as a fine powder and in that at least 10% of the solids have a particle size <10 μm and in that at least 10% of the solids have a particle size of >50 μm. 
     
     
         3 . Implant material according to  claim 1  or  2 , characterized in that the solids to >30% are comprised of salts of silicic acid or its condensates and/or salts of phosphoric acid or its condensates and/or salts of the glycerine phosphoric acid and/or salts of sulfuric acid and/or salts of carbonic acid. 
     
     
         4 . Implant material according to one of the  claims 1  to  3 , characterized in that the solids to >75% are comprised of calcium and/or magnesium salts and/or oxides and/or hydroxides of calcium and/or magnesium. 
     
     
         5 . Implant material according to  claim 3  or  4 , characterized in that the solids are comprised to >50% of calcium and/or magnesium phosphates. 
     
     
         6 . Implant material according to  claim 3  or  4 , characterized in that the calcium compounds are selected from monocalcium phosphate monohydrate (MCPM), monocalcium phosphate anhydrite (MCPA), dicalcium phosphate anhydrite (DCPA), dicalcium phosphate dihydrate (DCPD), octacalcium phosphate (OCP), α-tricalcium phosphate (α-TCP), β-tricalcium phosphate (β-TCP), amorphous calcium phosphate (ACP), hydroxyl apatite (HA), calcium-deficient hydroxyl apatite (CdHA), substituted hydroxyl apatite, non-stoichiometric hydroxyl apatite, nano hydroxyl apatite, tetracalcium phosphate (TTCP), calcium sulfate (CaSO 4 ), calcium sulfate hemihydrate (CaSO 4 ×0.5H 2 O), calcium sulfate dihydrate (CaSO 4 ×2 H 2 O), calciumoxide (CaO), calcium hydroxide (Ca(OH) 2 ), calcium carbonate (CaCO 3 ), calcium glycerophosphate, calcium citrate, calcium lactate, calcium acetate, calcium tartrate, calcium chloride (CaCl 2 ), calcium silicates and their mixtures with one another. 
     
     
         7 . Implant material according to  claim 3  or  4 , characterized in that the magnesium compounds are selected from magnesium hydrogen phosphate (MgHPO 4 ) in the form of the hydrates and as anhydrous substance, trimagnesium phosphate (Mg 3 (PO 4 ) 2 ), magnesium dihydrogen phosphate (Mg(H 2 PO 4 ) 2 ) in the form of the hydrates and as anhydrous substance, magnesium chloride (MgCl 2 ) in the form of the hydrates and as anhydrous substance, magnesium glycerophosphate, magnesium hydroxide (Mg(OH) 2 ), magnesium hydroxide carbonate, magnesium oxide (MgO), magnesium citrate, calcium magnesium carbonate (CaMg(CO 3 ) 2 , dolomite) and their mixtures with one another. 
     
     
         8 . Implant material according to  claim 3  or  4 , characterized in that the solids to >25% contain α- or β-tricalcium phosphate, tetracalcium phosphate, dicalcium phosphate anhydrite or amorphous calcium phosphate. 
     
     
         9 . Implant material according to one of  claims 3  to  7 , characterized in that the solids moreover contain ammonium salts that with one of the magnesium compounds cure to a magnesium ammonium phosphate solid material. 
     
     
         10 . Implant material according to one of  claims 3  to  7 , characterized in that the solids contain to >5% calcium or magnesium hydrogen phosphate as hydrate or anhydrous substance. 
     
     
         11 . Implant material according to one of the  claims 3  to  7 , characterized in that the solids to >10% contain calcium sulfate and in particular to >10% calcium sulfate hemihydrate. 
     
     
         12 . Implant material according to one of  claims 1 - 11 , characterized in that the at least one component contains a mineral powder mixture that in combination with the aqueous solution has a molar calcium/phosphate ratio of >1.35. 
     
     
         13 . Implant material according to one of the  claims 1 - 11 , characterized in that the at least one component contains a mineral powder mixture that in combination with the aqueous solution has a molar calcium/phosphate ratio of 0.9-1.35. 
     
     
         14 . Implant material according to one of the  claims 1 - 13 , characterized in that the solids are partially or completely dispersed in the carrier liquid and that the carrier liquid itself is soluble to less than 25% in water. 
     
     
         15 . Implant material according to one of the  claims 1 - 14 , characterized in that the carrier liquid contains dissolved, suspended or dispersed solids or liquids that in water are soluble to more than 1% (W/W), are greatly swellable in water, or in the chemical sense are miscible with water. 
     
     
         16 . Implant material according to one of the  claims 1 - 15 , characterized in that the carrier liquid is miscible with water and/or aqueous solutions in the physical sense and/or in that the carrier liquid contains substances that assist the formation of physical mixtures with water or aqueous solutions (emulsions) and stabilize it. 
     
     
         17 . Implant material according to one of the  claims 1 - 16 , characterized in that the carrier liquid is comprised of at least 2 substances that at normal conditions are liquid and wherein each of the substances to at least 0.1% is contained in the carrier liquid. 
     
     
         18 . Implant material according to one of the  claims 1 - 17 , characterized in that the carrier liquid to >50% is comprised of aliphatic hydrocarbons, esters, ethers, organic acids or mono-valent or multi-valent alcohols with a molecular weight of <2,500 or their mixtures. 
     
     
         19 . Implant material according to one of the  claims 1 - 18 , characterized in that the carrier liquid to >50% is comprised of esters of mono-valent and/or multi-valent alcohols with fatty acids. 
     
     
         20 . Implant material according to one of the  claims 1 - 18 , characterized in that the carrier liquid to >50% is comprised of esters or oligoesters of mono-valent or multi-valent alcohols with hydroxy acids, in particular of lactic acid, glycol acids, hydroxy butanoic acid or caprolactone or their mixtures, co-oligomers and/or stereoisomers. 
     
     
         21 . Implant material according to one of the  claims 1 - 18 , characterized in that the carrier liquid to >1% is comprised of oligomers or polymers and/or co-oligomers or copolymers of ethylene glycol and/or propylene glycol with one another and/or other building blocks, wherein the ethylene glycol and propylene glycol units together make up more than 50% by weight of the corresponding compound and wherein the compounds at normal conditions are liquid. 
     
     
         22 . Implant material according to one of the  claims 1  to  21 , characterized in that the dispersed solids are contained to 25% by weight up to 75% by weight in the paste, suspension or dispersion comprised of liquid and solids. 
     
     
         23 . Implant material according to one of the  claims 1 - 21 , characterized in that the dispersed solids are contained to >70% by weight in the paste, suspension or dispersion comprised of liquid and solids. 
     
     
         24 . Implant material according to one of the  claims 1 - 23 , characterized in that the paste, suspension or dispersion contains one or several surface-active agents in addition to suspended/dispersed solids and carrier liquid. 
     
     
         25 . Implant material according to one of the  claims 1 - 24  characterized in that the paste, suspension or dispersion contains iron oxides, clay minerals, silicon dioxide, barium sulfate or glycerine stearate as further highly dispersed solids that enhance the formation and stability of physical mixtures (emulsions). 
     
     
         26 . Implant material according to  claim 24  or  25 , characterized in that the paste, suspension or dispersion contains, in addition to suspended/dispersed solids carrier liquid, one or several surface-active agents and/or highly dispersed solids, dissolved or suspended polymers with a molecular weight of >2,500. 
     
     
         27 . Implant material according to one of the  claims 1 - 26 , characterized in that the paste, suspension or dispersion contains one or several dissolved or suspended pharmacological active ingredients. 
     
     
         28 . Implant material according to one of the  claims 1 - 27 , characterized in that it contains as a further component an aqueous solution or pure water. 
     
     
         29 . Implant material according to  claim 28 , characterized in that the aqueous solution contains substances that participate in the curing reaction and/or affect its reaction kinetics. 
     
     
         30 . Implant material according to  claim 28  or  29 , characterized in that the aqueous solution contains substances that increase the viscosity of the aqueous solution, in particular water-soluble and/or water-swellable polymers and/or highly dispersed solids. 
     
     
         31 . Implant material according to one of the  claims 28 - 30 , characterized in that non-reactive components of the mineral cement solids are contained partially or completely in the aqueous solution. 
     
     
         32 . Implant material according to one of the  claims 28 - 31 , characterized in that the aqueous solution contains substances that affect the crystal structure of the solid phases that are formed in the curing reaction, in particular anionic surface-active agents, magnesium salts, silicates, collagen, gelatin, hyaluronic acid, chondroitin sulfate, amino acids, its phosphorylated derivatives, vitamins and their derivatives, starch and its derivatives, chitosan and its derivatives, cellulose and its derivatives, polyacrylic acid and its derivatives or salts, and generally water-soluble and/or water-swellable polymers whose isoelectric point is <7. 
     
     
         33 . Implant material according to one of the  claims 28 - 32 , characterized in that the aqueous solution contains suspended and/or dissolved pharmacological active ingredients and/or excipients that affect the stability and/or the release kinetics of the active ingredients. 
     
     
         34 . Multi-component application system with a mixing device, comprising implant material according to one of the  claims 1  to  33 . 
     
     
         35 . Single component application system containing implant material according to one of the  claims 1  to  27  wherein it contains all substances required for triggering a curing reaction with the exception of water and upon introduction into an aqueous medium and/or contact with water-containing surfaces a curing reaction is spontaneous triggered. 
     
     
         36 . Use of implant materials according to one of the  claims 1  to  33  for producing bone cements, bone replacement materials, bone adhesives, tooth filling materials and/or implantable active ingredient carriers. 
     
     
         37 . Use of an implant material according to one of the  claims 1  to  33  in combination with application systems for augmenting osteoporotic or other pathologically modified bone areas and for filling bone defects of all kinds.