# US 8,784,551 B2 · Bone cement formula and bioresorbable hardened bone cement composites prepared with the same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,784,551 B2 - Document ID: US8784551B2 - Status: Granted - Kind: B2 - Application number: 12/907,091 - Filed: 2010-10-19 - Published: 2012-04-19 - Granted: 2014-07-22 - Earliest claimed: 2010-10-19 - Assignees: National Cheng Kung University - Applicants: Chien-Ping Ju; Jiin-Huey Chern Lin - Inventors: Chien-Ping Ju; Jiin-Huey Chern Lin - Web page: https://patentgrep.com/patent/US8784551B2 ## CPC - C04B 28/34: containing cold phosphate binders - A61L 24/0063: {Phosphorus containing materials, e.g. apatite} - A61L 27/46: with phosphorus-containing inorganic fillers - C04B 28/346: {the phosphate binder being present in the starting composition as a mixture of free acid and one or more phosphates} - C04B 41/009: {characterised by the material treated} - C04B 41/5092: {Phosphate cements} - A61L 2430/02: for reconstruction of bones; weight-bearing implants - C04B 2111/00836: {for medical or dental applications} - C04B: LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE {(roofing granules E04D7/005)}; CERAMICS (devitrified glass-ceramics C03C10/00); REFRACTORIES; TREATMENT OF NATURAL STONE - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) ## Abstract The present invention provides a bone cement formula having a powder component and a setting liquid component, wherein the powder component includes a calcium sulfate source and a calcium phosphate source with a weight ratio of the calcium sulfate source less than 65%, based on the total weight of the calcium sulfate source and the calcium phosphate source, and the setting liquid component comprises ammonium ion (NH4+) in a concentration of about 0.5 M to 4 M, wherein the calcium phosphate source includes tetracalcium phosphate (TTCP) and dicalcium phosphate in a molar ratio of TTCP to dicalcium phosphate of about 0.5 to about 2.5, and the calcium sulfate source is calcium sulfate hemihydrate (CSH), calcium sulfate dehydrate (CSD), or anhydrous calcium sulfate. ## Claims ### Claim 1 A bone cement composition comprising a powder component and a setting liquid component with a liquid to powder ratio of 0.20 cc/g to 0.50 cc/g, wherein the powder component comprises a calcium sulfate source and a calcium phosphate source with a weight ratio of the calcium sulfate source less than 65%, based on the total weight of the calcium sulfate source and the calcium phosphate source, and the setting liquid component comprises ammonium ion (NH4+) in a concentration of about 0.5 M to 4 M, wherein the calcium phosphate source comprises tetracalcium phosphate (TTCP) and dicalcium phosphate in a molar ratio of TTCP to dicalcium phosphate of about 0.5 to about 2.5, and the calcium sulfate source is calcium sulfate hemihydrate (CSH), calcium sulfate dehydrate (CSD), or anhydrous calcium sulfate. ### Claim 2 (depends on 1) The composition of claim 1, wherein the dicalcium phosphate is dicalcium phosphate anhydrous (DCPA). ### Claim 3 (depends on 1) The composition of claim 1, wherein the calcium sulfate source of the powder component is greater than 5%, and more is of 10% to 55%, based on the total weight of the calcium sulfate source and the calcium phosphate source powder. ### Claim 4 (depends on 1) The composition of claim 1, wherein the setting liquid component comprises ammonium ion (NH4+) in a concentration of about 1.0 M to 2.0M. ### Claim 5 (depends on 4) The composition of claim 4, wherein the setting liquid component is a solution of NH4H2PO4, (NH4)2HPO4, (NH4)3PO4·3H2O or mixtures thereof. ### Claim 6 (depends on 5) The composition of claim 5, wherein the setting liquid component is an aqueous solution of (NH4)2HPO4. ### Claim 7 (depends on 6) The composition of claim 6, wherein the setting liquid component further comprises citric acid or tartaric acid dissolved therein. ### Claim 8 (depends on 7) The composition of claim 7, wherein the setting liquid component has a pH of about 7.0 to about 9.0. ### Claim 9 (depends on 1) The composition of claim 1 further comprising a pore-forming agent which is to be dissolved in a solution when a hardened bone cement composite prepared therefrom is immersed in the solution. ### Claim 10 (depends on 9) The composition of claim 9, wherein the pore-forming agent is selected from the group consisting of LiCI, KCI, NaCI, MgCl2, CaCl2, NalO3, KI, Na3PO4, K3PO4, Na2CO3, amino acid-sodium salt, amino acid-potassium salt, glucose, polysaccharide, fatty acid-sodium salt, fatty acid-potassium salt, potassium bitartrate (KHC4H4O6), potassium carbonate, potassium gluconate (KC6H11O7), potassium-sodium tartrate (KNaC4H4O6·4H2O), potassium sulfate (K2SO4), sodium sulfate, sodium lactate and mannitol. ### Claim 11 (depends on 2) The composition of claim 2, wherein the calcium phosphate source is composed of TTCP and DCPA. ### Claim 12 (depends on 1) The composition of claim 1 further comprising living cells, a growth factor or a drug in the powder component or in the setting liquid component. ### Claim 13 A bone cement composition comprising a powder component and a setting liquid component with a liquid to powder ratio of 0.25 cc/g to 0.35 cc/g, wherein the powder component comprises a calcium sulfate source and a calcium phosphate source with a weight ratio of the calcium sulfate source less than 65%, based on the total weight of the calcium sulfate source and the calcium phosphate source, and the setting liquid component comprises ammonium ion (NH4+) in a concentration of about 0.5 M to 4 M, wherein the calcium phosphate source comprises tetracalcium phosphate (TTCP) and dicalcium phosphate in a molar ratio of TTCP to dicalcium phosphate of about 1, and the calcium sulfate source is calcium sulfate hemihydrate (CSH). ### Claim 14 (depends on 1) A process for preparing a hardened bone cement composite comprising forming a bone cement paste by mixing the powder component and the setting liquid component of the bone cement composition set forth in claim 1, and placing the paste at an environment to become set. ### Claim 15 (depends on 14) The process of claim 14, wherein said placing the paste at an environment to become set comprises shaping the paste in a mold, and removing the mold to form a block of hardened bone cement composite. ### Claim 16 (depends on 15) The process of claim 15 further comprising pressurizing said paste in said mold before said paste becomes set to remove a portion of liquid from said paste, so that a liquid to powder ratio of said paste decreases. ### Claim 17 (depends on 16) The process of claim 16, wherein the pressure applied to the paste in the mold is form about 1MPa to 500 MPa, preferably from 100 MPa to 500 MPa. ### Claim 18 (depends on 15) The process of claim 15 further comprising impregnating the block with an impregnating liquid for a period of time, so that a compressive strength of the resulting impregnated block removed from the impregnating liquid is increased compared to that of said block without said impregnating treatment. ### Claim 19 (depends on 18) The process of claim 18 wherein the impregnating liquid is a phosphate-containing solution. ### Claim 20 (depends on 19) The process of claim 19, wherein the phosphate-containing solution is an aqueous solution of (NH4)3PO4, (NH4)2HPO4, NH4H2PO4, K3PO4, K2HPO4, KH2PO4, Na3PO4, Na2HPO4, NaH2PO4, or H3PO4. ### Claim 21 (depends on 19) The process of claim 19, wherein said phosphate-containing solution has a phosphate concentration from about 0.1 M to about 6 M, preferably from about 1 M to about 3 M. ### Claim 22 (depends on 15) The process of claim 15, wherein the powder component of the bone cement composition contains a pore-forming agent, or a pore-forming agent is added during the mixing or is mixed with the paste before shaping the paste in a mold, and said process further comprises immersing said block of hardened bone cement composite in an immersing liquid to dissolve said pore-forming agent in the immersing liquid, creating pores therein, so that a porous block is formed. ### Claim 23 (depends on 22) The process of claim 22, wherein the pore forming agent is selected from the group consisting of LiCl, KCl, NaCl, MgCl2, CaCl2, NaIO3, KI, Na3PO4, K3PO4, Na2CO3, amino acid-sodium salt, amino acid-potassium salt, glucose, polysaccharide, fatty acid-sodium salt, fatty acid-potassium salt, potassium bitartrate (KHC4H4O6), potassium carbonate, potassium gluconate (KC6H11O7), potassium-sodium tartrate (KNaC4H4O6·4H2O), potassium sulfate (K2SO4), sodium sulfate, sodium lactate and mannitol. ### Claim 24 (depends on 22) The process of claim 22, wherein the immersing liquid is an acidic aqueous solution, a basic aqueous solution, a physiological solution, an organic solvent, or water. ### Claim 25 (depends on 24) The process of claim 24, wherein the immersing liquid is a phosphate-containing solution having a phosphate concentration from about 0.1 M to about 6 M. ### Claim 26 (depends on 25) The process of claim 25, wherein the phosphate-containing solution is an aqueous solution of (NH4)3PO4, (NH4)2HPO4, NH4H2PO4, K3PO4, K2HPO4, KH2PO4, Na3PO4, Na2HPO4, NaH2PO4, or H3PO4. ### Claim 27 (depends on 25) The process of claim 25, wherein said immersing liquid is water. ### Claim 28 (depends on 22) The process of claim 22 further comprising impregnating the porous block with an impregnating liquid for a period of time, so that a compressive strength of the resulting impregnated porous block removed from the impregnating liquid is increased compared to that of said porous block without said impregnating treatment. ### Claim 29 (depends on 28) The process of claim 28 wherein the impregnating liquid is a phosphate-containing solution. ### Claim 30 (depends on 29) The process of claim 29, wherein the phosphate-containing solution is an aqueous solution of (Nh4)3PO4, (NH4)2HPO4, NH4H2PO4, K3PO4, K2HPO4, KH2PO4, Na3PO4, Na2HPO4, NaH2PO4, or H3PO4. ### Claim 31 (depends on 29) The process of claim 29, wherein said phosphate-containing solution has a phosphate concentration from about 0.1 to about 6 M. ### Claim 32 (depends on 24) The process of claim 24 further comprising impregnating the porous block in a suspension of living cells or a solution of growth factor or drug to deposit the living cells, the growth factor or drug onto the porous block. ### Claim 33 (depends on 22) The process of claim 22, wherein the porous block has a porosity of 50-90 vol %. ### Claim 34 (depends on 14) The process of claim 14, wherein placing the paste at an environment to become set comprises filling a hole or cavity in a bone with the paste which becomes a hardened bone cement composite in-situ. ### Claim 35 (depends on 1) A method for treating a subject comprising forming a bone cement paste by mixing the powder component and the setting liquid component of the bone cement composition set forth in claim 1 and filling a hole or cavity in a bone with said bone cement paste which set hard in the hole or cavity in need of said treatment. ### Claim 36 (depends on 35) The method of claim 35 wherein said treatment is an orthopedic treatment or a dental treatment. ### Claim 37 (depends on 1) A method for treating a subject comprising forming a bone cement paste by mixing the powder component and the setting liquid component of the bone cement composition set forth in claim 1; forming a hardened bone cement composite from said paste; and implanting said hardened bone cement composite in said subject in need of said treatment. ### Claim 38 (depends on 37) The method of claim 37 wherein said treatment is an orthopedic treatment or a dental treatment, and said hardened bone cement composite is implanted in a bone of said subject. ### Claim 39 (depends on 37) The method of claim 37 wherein said implanting comprises breaking up said hardened bone cement composite into pellets and filling a hole or cavity in a bone of said subject with said pellets. ### Claim 40 (depends on 37) The method of claim 37 further comprising mixing a pore-forming agent with the powder component or with the paste, wherein said formation of the hardened bone cement composite comprises shaping the paste in a mold; removing the mold to form a block of hardened bone cement composite with the pore-forming agent embedded therein; and immersing said block of hardened bone cement composite with the pore-forming agent embedded therein in an immersing liquid to dissolve said pore-forming agent in the immersing liquid, creating pores therein, so that a porous block is formed, and thus said implanting comprises implanting said porous block in said subject in need of said treatment. ### Claim 41 (depends on 40) The method of claim 40, wherein said implanting comprises breaking up the porous block into pellets and filling a hole or cavity in a bone of said subject with said pellets. ### Claim 42 (depends on 24) The process of claim 24, wherein the immersing liquid is a phosphate-containing solution having a phosphate concentration from about 1 M to about 3 M. ### Claim 43 (depends on 29) The process of claim 29, wherein said phosphate-containing solution has a phosphate concentration from about 1 M to about 3 M. ### Claim 44 (depends on 19) The process of claim 19, wherein said phosphate-containing solution has a phosphate concentration from about 1 M to about 3 M.