# US 8,771,748 B2 · Rapid setting calcium phosphate cements > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,771,748 B2 - Document ID: US8771748B2 - Status: Granted - Kind: B2 - Application number: 11/134,051 - Filed: 2005-05-19 - Published: 2005-11-24 - Granted: 2014-07-08 - Earliest claimed: 2004-05-20 - Assignees: Skeletal Kinetics, LLC - Applicants: Brent R. Constantz; David Delaney; Duran Yetkinler - Inventors: Brent R. Constantz; David Delaney; Duran Yetkinler - Web page: https://patentgrep.com/patent/US8771748B2 ## CPC - C04B 28/344: {the phosphate binder being present in the starting composition solely as one or more phosphates} - A61K 33/42: Phosphorus; Compounds thereof - C04B 2103/12: Set accelerators - 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 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Methods are provided for producing compositions, e.g. pastes or clays, which rapidly set into high-strength calcium phosphate products. In the subject methods, dry reactants that include calcium and phosphate sources, as well as a monovalent cation dihydrogen phosphate salt, are combined with a setting fluid and the combined reactants are mixed to produce the settable composition. A feature of the invention is that cements rapidly set into high strength product compositions. Also provided are the compositions themselves as well as kits for preparing the same. The subject methods and compositions produced thereby find use in a variety of applications, including hard tissue repair applications. ## Claims ### Claim 1 A method of producing a calcium phosphate composition that sets into a calcium phosphate mineral containing product, said method comprising: combining: (a) a setting fluid; (b) dry reactants comprising: (i) calcium and phosphate sources comprising a first particulate calcium and/or phosphate reactant having a mean particle size of 8 μm or less and narrow particle size distribution; and a second calcium and/or phosphate reactant having a mean particle size that is 10 μm or greater; and (ii) a monovalent cation dihydrogen phosphate salt; in a ratio of (a) to (b) sufficient to produce said calcium phosphate mineral containing product that is resorbable over time when implanted into a physiological site, wherein the standard deviation of the particles that make up the first reactant does not exceed 4.0 um. ### Claim 2 (depends on 1) The method according to claim 1, wherein said monovalent cation dihydrogen phosphate salt includes at least one water of hydration. ### Claim 3 (depends on 1) The method according to claim 1, wherein said monovalent cation dihydrogen phosphate salt is described by the formula: Y+H2PO4.(H2O)n where: Y+ is a monovalent cation; and n is an integer from 0 to 2. ### Claim 4 (depends on 3) The method according to claim 3, wherein Y+ is Na+. ### Claim 5 (depends on 1) The method according to claim 1, wherein said monovalent cation dihydrogen phosphate salt is NaH2PO4 or NaH2PO4.H2O. ### Claim 6 (depends on 1) The method according to claim 1, wherein said monovalent cation dihydrogen phosphate salt is present in said composition in an amount ranging from about 0.10 to about 10 wt %. ### Claim 7 (depends on 1) The method according to claim 1, wherein said method further comprises combining said dry reactants and setting fluid with an emulsifying agent. ### Claim 8 (depends on 7) The method according to claim 7, wherein said emulsifying agent is a cellulose ether. ### Claim 9 (depends on 8) The method according to claim 8, wherein said cellulose ether is carboxymethylcellulose. ### Claim 10 (depends on 1) The method according to claim 1, wherein said composition attains a strength of about 50 Newtons or greater in 3 minutes. ### Claim 11 (depends on 1) The method according to claim 1, wherein said composition attains a strength of about 250 Newtons or greater in 6 minutes. ### Claim 12 (depends on 1) A composition that sets into a calcium phosphate containing product, wherein said composition is produced by the method according to claim 1. ### Claim 13 (depends on 12) The composition according to claim 12, wherein said composition attains a strength of about 50 Newtons or greater in 3 minutes. ### Claim 14 (depends on 1) A method of repairing a hard tissue defect, said method comprising: applying to the site of said defect a composition that sets into a calcium phosphate containing product, wherein said composition is produced by the method according to claim 1. ### Claim 15 A kit for use in a preparing a composition that sets in an in vivo fluid environment into a calcium phosphate product, said kit comprising: (a) dry reactants comprising: (i) calcium and phosphate sources comprising a first particulate calcium and/or phosphate reactant having a mean particle size of 8 μm or less and narrow particle size distribution; and a second calcium and/or phosphate reactant having a mean particle size that is 10 μm or greater; and (ii) a monovalent cation dihydrogen phosphate salt; and (b) a setting fluid or components for producing the same. ### Claim 16 (depends on 15) The kit according to claim 15, wherein said kit further comprises an emulsifying agent. ### Claim 17 (depends on 16) The kit according to claim 16, wherein said emulsifying agent is a cellulose ether. ### Claim 18 (depends on 17) The kit according to claim 17, wherein said cellulose ether is carboxymethylcellulose. ### Claim 19 (depends on 15) The kit according to claim 15, wherein said kit further comprises a mixing element for preparing a settable composition from said dry reactants and setting fluid. ### Claim 20 (depends on 15) The kit according to claim 15, wherein said kit further comprises a delivery element. ### Claim 21 A method of producing a calcium phosphate composition that sets into a calcium phosphate mineral containing product, said method comprising: combining: (a) a setting fluid; (b) dry reactants comprising: (i) calcium and phosphate sources comprising a first particulate calcium and/or phosphate reactant having a mean particle size of 8 μm or less and narrow particle size distribution; and a second calcium and/or phosphate reactant having a mean particle size that is 10 μm or greater; and (ii) a monovalent cation dihydrogen phosphate salt; in a ratio of (a) to (b) sufficient to produce said calcium phosphate mineral containing product that is resorbable over time when implanted into a physiological site, wherein samples of said composition attain an average setting strength of about 50 Newtons or greater in 3 minutes. ### Claim 22 (depends on 21) The method according to claim 21, wherein samples of said composition attain an average setting strength of about 75 Newtons or greater in 3 minutes. ### Claim 23 (depends on 21) The method according to claim 21, wherein samples of said composition attain an average setting strength of about 100 Newtons or greater in 3 minutes. ### Claim 24 (depends on 21) The method according to claim 21, wherein said composition attains a strength of about 150 Newtons or greater in 3 minutes. ### Claim 25 (depends on 21) The method according to claim 21, wherein said composition attains a strength of about 175 Newtons or greater in 3 minutes. ### Claim 26 (depends on 21) The method according to claim 21, wherein said composition attains a strength of about 250 Newtons or greater in 3 minutes. ### Claim 27 (depends on 1) The method according to claim 1, wherein the mean particle size of the second reactant is at least 2 times larger than the mean particle size of the first reactant.