Solid-state method for producing functionalized calcium phosphate hybrid organic/inorganic chemical systems for dental remineralization applications

Abstract

A method of repairing weakened teeth, including combining a first predetermined amount of an inorganic calcium source with a second predetermined amount of an organic material to define a mixture, placing the mixture in a milling vessel operationally connected to a planetary mill, introducing milling media into the milling vessel, milling the mixture to impart sufficient kinetic energy to break down the organic and inorganic materials into substantially smaller intermediate particles and fuse the intermediate particles together to yield functionalized molecules having both organic and inorganic chemical characteristics, combining a functionalized calcium phosphate/organic compound with a fluoridated formulation to define a hybrid system, and applying the hybrid system to the weakened teeth.

1 . A method of repairing weakened teeth, comprising:
 a) combining a first predetermined amount of an inorganic calcium source with a second predetermined amount of an organic material to define a mixture;   b) placing the mixture in a milling vessel operationally connected to a planetary mill;   c) introducing milling media into the milling vessel;   d) milling the mixture to impart sufficient kinetic energy to break down the organic and inorganic materials into substantially smaller intermediate particles and fuse the intermediate particles together to yield functionalized molecules having both organic and inorganic chemical characteristics;   e) combining a functionalized calcium phosphate/organic compound with a fluoridated formulation to define a hybrid system;   f) applying the hybrid system to the weakened teeth.   
     
     
         2 . The method of  claim 1  wherein the functionalized calcium phosphate/organic compound generally includes between 0.5 and 99.5 weight percent of a calcium phosphate mineral including tricalcium phosphate and generally includes between 0.5 and 99.5 weight percent of an organic component. 
     
     
         3 . The method of  claim 1  wherein the organic material is a neutral surfactant or polyether and is selected from the group including polyethylene glycol (PEG), polypropylene glycol (PPG), poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol); and wherein the material has no charges manifested in its structure; and wherein the material is terminated with hydroxyl groups; and wherein those materials have ether linkage and ether monomer lengths between n=13 and n=150. 
     
     
         4 . The method of  claim 1  wherein the organic component is a carboxylic acid and is selected from the group including fumaric acid, acrylic acid, malic acid, citric acid, maleic acid, stearic acid and combinations thereof; and wherein those materials having carboxylic acid character; and wherein the carboxylic acid functional groups are connected via saturated or unsaturated carbon bonds. 
     
     
         5 . The method of  claim 1  wherein the organic component is a negative surfactant and is selected from the group including sodium lauryl sulfate, sodium lauryl ether sulfate, ammonium lauryl sulfate, N,N-Dimethyl-N-[3-(sulfoxy)propyl]-1-nonanaminium hydroxide inner salt, sodium dodecylbenzenesulfonate, poly(ethylene glycol) 4-nonylphenyl 3-sulfopropyl ether potassium salt, doctyl sulfosuccinate sodium salt and combinations thereof; and wherein the cationic species of the material are ionically bound; and wherein the material has anionic functionalities; and wherein the aliphatic character of the material extends up to at least 12 carbon atoms; and wherein the material manifests ethoxy functionalities (OCH 2 CH 2 ) n ). 
     
     
         6 . The method of  claim 1  wherein the organic component is a positive surfactant and is selected from the group including cetylpyridinium chloride, pyridinium chloride, hexadecyltrimethylammonium bromide, N,N-Dimethyl-N-[3-(sulfoxy)propyl]-1-decanaminium hydroxide inner salt and combinations thereof; and wherein the materials have quaternary ammonium cation character manifested in a conjugated carbon ring; and wherein the materials have anionic species are ionically bound; and wherein the aliphatic chain length extends up to at least 17 carbon atoms. 
     
     
         7 . The method of  claim 1  wherein the organic component is a neutral surfactant or polyester and is selected from the group including polycaprolactone, poly(ethylene oxide)-block-polycaprolactone, polycaprolactone diol, polycaprolactone triol and combinations thereof; and wherein the materials are neutral; and wherein the materials manifest ester monomer lengths between at least 10 and 150; and wherein the material manifests non-ring ester linkages (O—(CH 2 ) 5 —C═O)). 
     
     
         8 . The method of  claim 1  wherein the hybrid system is added to a member of the group including toothpaste, dental gel, varnish, oral rinse, to define a hybrid oral dental application. 
     
     
         9 . A method of reducing tooth sensitivity in a patient, comprising:
 a) mechanochemically fusing an organic material with an inorganic material to yield a functionalized complex;   b) applying the functionalized complex to the tooth surface of a patient; and   c) occluding tubules opening onto the tooth surface.   
     
     
         10 . The method of  claim 9 , wherein the organic component is selected from the group including anionic surfactants, cationic surfactants, neutral surfactants, carboxylic acids, polymers, copolymers, block copolymers, and combinations thereof and wherein the inorganic component contains calcium. 
     
     
         11 . The method of  claim 10  wherein the inorganic component is tricalcium phosphate. 
     
     
         12 . A dental composition, comprising:
 A functionalized complex including an organic component coupled to an inorganic component; and   a fluoride-containing component;   wherein the coupling of the organic and inorganic components is achieved through mechanochemically reacting organic precursors and inorganic precursors in a high-energy planetary ball mill;   wherein the mechanochemical milling occurs substantially in the solid state; and   wherein the mechanochemical milling is sufficiently energetic to break down the organic precursors and inorganic precursor into organic and inorganic components and to fuse organic and inorganic components into functionalized complexes.   
     
     
         13 . The dental composition of  claim 12  wherein the organic precursor is selected from the group including anionic surfactants, cationic surfactants, neutral surfactants, carboxylic acids, polymers, copolymers, block copolymers, and combinations thereof; wherein the inorganic precursor contains calcium; and wherein the fluoride-containing component is aqueous sodium fluoride. 
     
     
         14 . The dental composition of  claim 13  wherein the inorganic precursor is tri-calcium phosphate. 
     
     
         15 . The dental composition of  claim 12  wherein the functionalized complex is incorporated into a medium selected from the group including gels, varnishes, pastes, rinses, adhesives, filling materials, reconstructive materials and combinations thereof. 
     
     
         16 . A method of reminerzalizing a tooth, comprising:
 a) mechanochemically combining an organic precursor with a calcium-containing inorganic precursor to yield a functionalized nanocomplex;   b) introducing the functionalized nanocomplex to a mineral-depleted tooth; and   c) increasing the mineral content of the tooth;   wherein the functionalized nanocomplex is a surfactant-coated mineral.   
     
     
         17 . The method of  claim 16 , wherein the organic precursor is selected from the group including anionic surfactants, cationic surfactants, neutral surfactants, and combinations thereof; wherein the inorganic precursor is tri-calcium phosphate. 
     
     
         18 . The method of  claim 17  wherein the organic precursor is polyethylene glycol. 
     
     
         19 . A method of enhancing the bioavailability of fluoride in a dental composition, comprising:
 a) mechanochemically synthesizing a nanocomplex material from an inorganic calcium-containing precursor and an organic precursor;   b) combining the nanocomplex material with an aqueous fluoride source to yield a dental treatment composition;   c) introducing the dental treatment composition to a patient's tooth;   wherein the bioactivity of the aqueous fluoride source is diminished by no more than 50 percent.   
     
     
         20 . The method of  claim 19  wherein the aqueous fluoride source is aqueous sodium fluoride and wherein the dental treatment composition contains between 0.5 and 20 weight percent hybrid calcium phosphate material. 
     
     
         21 . The method of  claim 20  wherein the organic precursor is polyethylene glycol. 
     
     
         22 . The method of  claim 21  wherein the polyethylene glycol has a molecular weight of between 600 and 1500 Da. 
     
     
         23 . The method of  claim 19  wherein the dental treatment composition includes between 0.1 and 10 weight percent sodium lauryl sulfate. 
     
     
         24 . A product for treating dental disorders, comprising:
 a tooth surface introduction medium; and   a dental treatment complex mixed with the tooth surface introduction medium;   wherein the dental treatment complex is formed by mechanochemically combining an organic precursor with a calcium-containing inorganic precursor; and   wherein the tooth surface introduction medium is selected from the group including gels, pastes, varnishes, fillers, reconstructives and rinses.   
     
     
         25 . The dental product of  claim 24  wherein the organic precursor is selected from the group including anionic surfactants, cationic surfactants, neutral surfactants, carboxylic acids, polymers, copolymers, block copolymers, and combinations thereof and where the inorganic precursor is tri-calcium phosphate. 
     
     
         26 . The dental product of  claim 25  wherein the organic precursor is a polymer. 
     
     
         27 . The dental product of  claim 26  wherein the organic precursor is polyethylene glycol. 
     
     
         28 . The dental product of  claim 24  wherein aqueous sodium fluoride is mixed with the tooth surface introduction medium. 
     
     
         29 . A method of treating a tooth to prevent dental disorders, comprising:
 a) mechanochemically combining an inorganic calcium-containing precursor and an organic precursor to yield a dental treatment complex;   b) combining the dental treatment complex with an aqueous fluoride source to yield a dental treatment composition;   c) introducing the dental treatment complex to a tooth;   d) reinforcing the tooth to resist the formation of caries and other dental disorders.   
     
     
         30 . The method of  claim 29  wherein the inorganic precursor is a calcium phosphate and wherein the organic precursor is a polymer. 
     
     
         31 . The method of  claim 30  wherein the polymer is polyethylene glycol and wherein the polymer has a molecular weight of between 600 and 1500 Da.