# US 12,109,284 B2 · Compositions comprising fluoride and calcium and method for preparing them > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,109,284 B2 - Document ID: US12109284B2 - Status: Granted - Kind: B2 - Application number: 16/347,948 - Filed: 2017-11-07 - Published: 2019-09-12 - Granted: 2024-10-08 - Earliest claimed: 2016-11-08 - Assignees: Dentherapy Ltd - Applicants: Dentherapy Ltd - Inventors: David Andrew Smillie; Richard James Willson - Web page: https://patentgrep.com/patent/US12109284B2 ## CPC - A61K 8/24: Phosphorous; Compounds thereof - A61K 8/19: containing inorganic ingredients - A61K 8/64: Proteins; Peptides; Derivatives or degradation products thereof - A61Q 11/00: Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses - A61K 2800/52: Stabilizers - A61K 2800/805: Corresponding aspects not provided for by any of codes A61K2800/81 - A61K2800/95 - A61K 2800/92: Oral administration - 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) - A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS ## Abstract The present invention relates to methods for preparing compositions comprising calcium and fluoride, and, in particular, to methods for preparing compositions comprising calcium that is stabilised with a stabilising agent and fluoride. For example, the method is for the preparation of compositions comprising amorphous calcium phosphate stabilised by phosphopeptides, and free fluoride. The invention also extends to various compositions produced by such methods, including oral care products. ## Claims ### Claim 1 A meth of preparing an oral care product having as a constituent thereof a liquid composition comprising soluble or at least a metastable stabilised amorphous calcium phosphate and fluoride, the method comprising: a) providing monofluorophosphate, a source of calcium ions, a source of phosphate ions, and a calcium phosphate stabilising agent, wherein the calcium phosphate stabilising agent comprises full length osteopontin and/or a long N-terminal fragment of osteopontin: b) mixing said source of calcium ions and said source of phosphate ions together with the calcium phosphate stabilising agent in a liquid medium in order to form a stabilised amorphous calcium phosphate complex; c) mixing the monofluorophosphate with the source of calcium ions, source of phophate ions, calcium phosphate stabilising agent and/or stabilised amorphous calcium phosphate complex in the liquid medium; wherein the monofluorophosphate, the source of calcium ions, the source of phosphate ions, and the calcium phosphate stabilising agent are all mixed together in a single reaction where precipitation is prevented; wherein the monofluorophosphate is mixed with the source of calcium ions, the source of phosphate ions, and the calcium phosphate stabilising agent before formation of the stabilised calcium phosphate complex has completed or has reached an equilibrium point, thereby producing a liquid composition comprising a soluble or at least a metastable stabilised amorphous calcium phosphate and fluoride; and incorporating the liquid composition into an oral care product. ### Claim 2 (depends on 1) The method according to claim 1 wherein the monofluorophosphate, source of calcium ions, source of phosphate ions, and calcium phosphate stabilising agent are added to a single reaction vessel with the liquid medium and mixed together and allowed to react together. ### Claim 3 (depends on 1) The method according to claim 1 comprising storing the liquid composition under suitable conditions for monofluorophosphate to decompose to release fluoride into the liquid medium. ### Claim 4 (depends on 1) The method according to claim 1 wherein the source of calcium ions is a soluble calcium salt. ### Claim 5 (depends on 1) The method according to claim 1 wherein the source of calcium ions is calcium chloride. ### Claim 6 (depends on 1) The method according to claim 1 wherein the source of phosphate ions is a soluble phosphate salt. ### Claim 7 (depends on 1) The method according to claim 1 wherein the source of phosphate ions is sodium phosphate. ### Claim 8 (depends on 1) The method according to claim 1 wherein the liquid medium is water. ### Claim 9 (depends on 1) The method according to claim 1 wherein the final pH of the liquid composition is greater than 7. ### Claim 10 (depends on 1) The method according to claim 1 comprising adding one or more of the following: a pH buffering agent, alcohol, humectant, surfactant, preservative, flavouring agent, cooling agent, sweetening agent, colouring agent, and anti-caries agent. ### Claim 11 (depends on 1) The method according to claim 1 wherein the oral care product is an oral spray or mouthwash. ### Claim 12 (depends on 4) The method according to claim 4 wherein the calcium salt is a calcium salt having a solubility of 5 g of salt per 100 ml of liquid medium or higher. ### Claim 13 (depends on 4) The method according to claim 4 wherein the calcium salt is a calcium salt having a solubility of 10 g of salt per 100 ml of liquid medium or higher. ### Claim 14 (depends on 4) The method according to claim 4 wherein the calcium salt is a calcium salt having a solubility of 50 g of salt per 100 ml of liquid medium or higher. ### Claim 15 (depends on 1) The method according to claim 1 wherein the source of phosphate ions is a soluble phosphate salt having a solubility of 5 g of salt per 100 ml of liquid medium or higher. ### Claim 16 (depends on 1) The method according to claim 1 wherein the source of phosphate ions is a soluble phosphate salt having a solubility of 10 g of salt per 100 ml of liquid medium or higher. ### Claim 17 (depends on 1) The method according to claim 1 wherein the source of phosphate ions is a soluble phosphate salt having a solubility of 50 g of salt per 100 ml of liquid medium or higher. ### Claim 18 (depends on 1) The method according to claim 1 wherein the source of phosphate ions is disodium hydrogen phosphate and/or trisodium phosphate. ### Claim 19 (depends on 1) The method according to claim 1, wherein the calcium phosphate stabilising agent is a mixture comprising full length osteopontin and the long N-terminal fragment of osteopontin. ### Claim 20 (depends on 19) The method according to claim 19, wherein the calcium phosphate stabilising agent is a mixture comprising 5-40% (w/w) full length osteopontin and 60-95% (w/w) of the long N-terminal fragment of osteopontin.