Remineralizing toothpaste

Abstract

Oral care compositions having a betaine compound of Formula I, a source of fluoride ions, a source of calcium ions, and water are described. Also described are oral care compositions further having a thickening silica and an abrasive agent. The oral care compositions are free of calcium fluoride and calcium phosphate precipitates and phase stable without requiring sodium lauryl sulfate. Also described are methods of preparing and using the oral care compositions.

Description

PA200087US01REMINERALIZING TOOTHPASTEBACKGROUND

[0001] Surfactants, such as sodium lauryl sulfate (“SLS”), are used in toothpastes to prevent phase separation and provide beneficial cleaning and foaming properties. However, many surfactants can adversely affect the integrity of the oral mucosa resulting in ulceration of soft tissues, dryness of the mouth, and even tooth sensitivity.

[0002] Many toothpastes aim to remineralize teeth in addition to the removal of plaque, tartar, and stains. Hydroxyapatite and fluorapatite are the remineralizing substances of interest, but enamel and dentin do not readily uptake said substances. Instead, hydroxyapatite and fluorapatite may be formed within the tooth structures upon exposure to calcium, phosphate, and fluoride ions. However, formulating these ions together is a challenge since calcium fluoride and calcium phosphate may readily form, both of which are sparingly bioavailable for remineralization. While sources of calcium, phosphate, and fluoride ions have been successfully incorporated into oral care compositions, the toothpastes typically include SLS, which may impede the release of said ions. Moreover, it has been reported that aged SLS, or rather the oxidative degradation products thereof, promote premature apatite formation. Thus, the remineralization potential of SLS-containing toothpastes has a shortened storage life.

[0003] What is needed is a safer remineralizing toothpaste that is stable against phase separation without the need for SLS surfactant.SUMMARY

[0004] In one embodiment, an oral care composition is described. The oral care composition includes a betaine compound, a source of fluoride ions, a source of calcium ions, a silica as a thickening agent, an abrasive agent, and water. The betaine compound represented by Formula I:R1-C(O)-Y-R2-N+(R3)2-R4-C(O)-O- (I), wherein:R1is a Ce-Cis alkyl or a Ce-Cis alkenyl,Y is -O- or -N(R5)-,R2is a C2-C8 alkylene, each R3is independently a Ci-Ce alkyl,R4is a C1-C4 alkylene, andR5is -H or a C1-C4 alkyl.

[0005] In one embodiment, a method for preparing an oral care composition of the present disclosure is described. The method includes providing, combining, and mixing a betaine compoundof Formula I, a source of fluoride ions, a source of calcium ions, a silica as a thickening agent, an abrasive agent, and water to form the oral care composition.

[0006] In one embodiment, a method for treating a tooth surface is described. The method includes contacting an oral care composition of the present disclosure to the tooth surface.

[0007] In one embodiment, a method for cleaning and remineralizing a tooth surface is described. The method includes contacting an oral care composition of the present disclosure to the tooth surface.

[0008] In one embodiment, a kit is described. The kit includes an oral care composition of the present disclosure and a set of instructions directing a user to contact the oral care composition to the tooth surface.DETAILED DESCRIPTION

[0009] The present disclosure describes phase-stable and precipitate-free (i.e., free of calcium fluoride and even calcium phosphate precipitates) oral care compositions (e.g., toothpaste) without requiring SLS surfactant. Fluoride ions, calcium ions, and even phosphate ions are incorporated within the oral care composition and are made bioavailable by the presence of a betaine compound. Without wishing to be bound by theory, it is believed that the betaine compound may provide a charged network in water, even in the presence of thickeners and abrasives, that binds or otherwise shelters calcium ions, thereby preventing the precipitation of calcium phosphate and / or calcium fluoride. Phase separation and precipitation was observed when other surfactants, such as SLS, were used. In other words, networks involving other surfactants were determined to not be stable or strong enough to shield the calcium cations from fluoride or phosphate ions, resulting in the formation of large water-insoluble crystals.

[0010] The present disclosure provides a remineralizing toothpaste lliat does not require SLS surfactant for stability and the lack of SLS prolongs the shelf life in terms of remineralization potential. Moreover, the remineralizing toothpaste of the present disclosure will not di rupt the protective mucin layer on soft tissues.Definitions

[0011] As used herein, “about” means ± 10 percent of a given value. For example, about 10 means 9 to 11.

[0012] As used herein, “chelating complex” refers to a combination of a chelator compound and a multivalent cation (e.g., calcium), wherein the multivalent cation is ionically bound to the chelator compound via two atoms within the chelator compound, each of the two atoms having a lone pair of electrons.

[0013] As used herein, phrases similar to “component A and component B present in a weight ratio of x:y” means that component A corresponds to value “x” and component B corresponds to value “y.”When referring to weight ratios of “at least x:y” or “at or above x:y” it is meant that value “y” remains constant for any increasing weight ratio. In other words, a weight ratio of at least “1: 1” includes weight ratios of 2: 1, 3: 1, 4: 1 and the like, and does not include weight ratios of 1:2, 1:3, 1:4, and the like.

[0014] As used herein, “exclude” means that the referenced substance is not present, i.e., 0 wt.%.

[0015] As used herein, the phrase “one or more of’ such as used in the phrase “one or more of A and B” or “one or more of at least one A and at least one B” means a composition may include at least one A, more than one A, at least one B, more than one B, at least one A and at least one B, more than one A and more than one B. In other words, the phrase does not mean the composition must have at least one of each of A and B.

[0016] As used herein, “organic” defines a compound having carbon, whereas “inorganic” defines a compound without carbon. An “organic phase” includes all organic compounds. An “inorganic phase” includes all inorganic compounds.

[0017] As used herein, “paste” refers to a substance that is solid until a load or stress is applied, at which point it flows like a liquid. Pastes can include suspension of a solid in a carrier.

[0018] As used herein, “viscosity” is a property measured using a ThermoHaake Rotovisco 1 device with a plate / plate system (diameter 20 mm) and a slit of 0.2 mm. The viscosity values for each shear rate (e.g., 10 1 / s to 100 1 / s in 10 1 / s steps), with a delay of 5 seconds before collecting data. This method of measurement corresponds to DIN 53018-1. The viscosity values described herein are reported at 20 °C at a shear rate of 1 / s, unless otherwise stated.

[0019] As used herein, “soluble” refers to at least 1 g of a component A completely dissolved (no visible cloudiness, precipitate, or phase separation) in 30 mL or less component B (e.g., water) at a temperature range of about 20 °C to about 23 °C and at atmospheric pressure (i.e., 760 mm / Hg). It is to be understood that the conditions to determine solubility only include the component A and the component B, i.e., no added salts, orthe like. Thus, a “water-soluble compound” describes a compound in which at least 1 g of said compound that dissolves completely in 30 mL water, or less.ORAL CARE COMPOSITIONS

[0020] In various embodiments, an oral care composition that is aqueous and free of precipitates is described. The oral care composition may include a betaine compound, a source of fluoride ions, a source of calcium ions, optionally a source of phosphate ions, and water. The betaine compound may be represented by Formula I:R1-C(O)-Y-R2-N+(R3)2-R4-C(O)-O- (I), wherein:R1is a Ce-Cis alkyl or a Ce-Cis alkenyl,Y is -O- or -N(R5)-,R2is a C2-C8 alkylene, eachR3is independently a Ci-Ce alkyl,R4is a C1-C4 alkylene, andR5is -H or a C1-C4 alkyl.

[0021] In various embodiments, an oral care composition is described. The oral care composition may include a betaine compound, a source of fluoride ions, a source of calcium ions, optionally a source of phosphate ions, a silica as a thickening agent, an abrasive agent, and water. The betaine compound may be represented by Formula I:R1-C(O)-Y-R2-N+(R3)2-R4-C(O)-O- (I), wherein:R1is a C6-C18 alkyl or a Ce-Cis alkenyl,Y is -O- or -N(R5)-,R2is a C2-C8 alkylene, eachR3is independently a Ci-Ce alkyl,R4is a C1-C4 alkylene, andR5is -H or a C1-C4 alkyl.

[0022] In some embodiments, any of the oral care compositions may further include a source of phosphate ions.

[0023] In some embodiments, any of the oral care compositions may further include an organic thickener.

[0024] In some embodiments, any of the oral care compositions may further include a buffering agent.

[0025] In some embodiments, any of the oral care compositions may further include a sweetener.

[0026] In some embodiments, any of the oral care compositions may further include a desensitizing agent.

[0027] In some embodiments, any of the oral care compositions may further include anionic surfactants, cationic surfactants, nonionic surfactants, or any combination thereof. In some embodiments, the oral care composition may specifically exclude sodium lauryl sulfate. In some embodiments, any of the oral care compositions may include surfactants with the combination of the betaine of Formula I. In other embodiments, any of the oral care compositions may exclude anionic surfactants, cationic surfactants, nonionic surfactants, or a combination thereof. In other embodiments, any of the oral care compositions may exclude surfactants other than the betaine of Formula I.

[0028] In some embodiments, any of the oral care compositions may further include synthetic polymeric components having organic acid group(s) or conjugates thereof (e.g., carboxylic acids or carboxylates, phosphonic acids or phosphorates, sulfonic acids or sulfonates, or the like). In other embodiments, any of the oral care compositions may exclude natural or synthetic polymericcomponents having organic acid group(s) or conjugates thereof. In some embodiments, the oral care composition may specifically exclude carboxylated cellulose, such as carboxymethyl cellulose (CMC).

[0029] In some embodiments, any of the oral care compositions may further include enzymes. In other embodiments, any of the oral care compositions may exclude enzymes.

[0030] In some embodiments, any of the oral care compositions may further include a chelator compound.

[0031] In some embodiments, any of the oral care compositions may be characterized by a viscosity of about 10,000 cP to about 800,000 cP at 20 °C. For example, the oral care composition may be characterized by a viscosity (cP) of about 10,000; 25,000; 50,000; 75,000; 100,00; 125,000; 150,000; 175,000; 200,000; 225,000; 250,000; 275,000; 300,000; 325,000; 350,000; 375,000; 400,000; 450,000; 500,000; 550,000; 600,000; 650,000; 700,000; 750,000; or 800,000, or a value within a range between any of the preceding values, e.g., between about 100,000 cP to 600,000 cP, or the like.

[0032] In some embodiments, any of the oral care compositions may be characterized as a colloid.

[0033] In some embodiment, any of the oral care compositions may be characterized as paste.Pastes of the present disclosure exclude liquid phase separation.

[0034] In some embodiments, any of the oral care compositions may be characterized by a pH of about 5.5 to about 8.5. For example, the oral care composition may be characterized by a pH of about 5.5, 5.8, 6.0, 6.2, 6.5, 6.8, 7.0, 7.2, 7.5, 7.8, 8.0, 8.2, or 8.5, or a value within a range between any of the preceding values, e.g., between about 5.5 and about 6.5, or the like.

[0035] In many embodiments, the oral care composition may be a toothpaste.

[0036] Further details are provided below.Betaine Compound

[0037] Without wishing to be bound by theory, it is believed that the betaine compound serves to stabilize calcium within the aqueous system through micelle formation, or otherwise a nano-size or submicron-size domain formation. It other words, the betaine compound prevents the precipitation of insoluble calcium salts, such as calcium fluoride and calcium phosphate. Furthermore, for oral care compositions having an organic thickener, the betaine compound was found to be essential to keeping the oral care composition uniform (i.e., no phase separation).

[0038] The betaine compound is represented by Formula I:R1-C(O)-Y-R2-N+(R3)2-R4-C(O)-O- (I), wherein:R1is a Ce-Cis alkyl or a Ce-Cis alkenyl,Y is -O- or -N(R5)-,R2is a C2-C8 alkylene, each R3is independently a Ci-Ce alkyl,R4is a C1-C4 alkylene, andR5is -H or a C1-C4 alkyl.

[0039] In some embodiments, R1is a Ce-Cis alkyl. R1can be an alkyl selected to have 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbons, or a number of carbons within a range between any of the preceding values, e.g., a Ce-Cn alkyl.

[0040] In some embodiments, R1is a Ce-Cis alkenyl. R1can ben an alkenyl selected to have 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbons, or a number of carbons within a range between any of the preceding values, e.g., a Ce-Cn alkenyl.

[0041] In some embodiments, Y is -N(R5)-. In some embodiments, Y is -N(R5)- and R5is -H. In other embodiments, Y is -N(R5)- and R5is C1-C4 alkyl. R5can be an alkyl selected to have 1, 2, 3, or 4 carbons, or a number of carbons within a range between any 0 the preceding values, e.g., C1-C3 alkyl. In some embodiments, R5is methyl.

[0042] In some embodiments, R2is a C2-C8 alkylene. R2can be an alkylene selected to have 2, 3, 4, 5, 6, 7, or 8 carbons, or a number of carbons within a range between any of the preceding values, e.g., C2-C4 alkylene.

[0043] In some embodiments, each R3is independently selected from Ci-Ce alkyl. R3can be an alkyl selected to have 1, 2, 3, 4, 5 or 6 carbons, or a number of carbons within a range between any of the preceding values, e.g., C1-C3 alkyl. In some embodiments, each R3is methyl.

[0044] In some embodiments, R4is a C1-C4 alkylene. R4can be selected to have 1, 2, 3, or 4 carbons, or a number of carbons within a range between any of the preceding values, e.g., C1-C2 alkylene. In some embodiments, R4is methylene.

[0045] In some embodiment, the betaine compound may be represented by Formula la:

[0046] In some embodiments, the betaine compound may be represented by Formula lb:

[0047] In many embodiments, the betaine compound may be present in an amount of about 0.025 wt% to about 5.0 wt% with respect to the weight of the oral care composition. For example, the crosslinked polyacrylic acid may be present in an amount (wt%) of about 0.025, 0.05, 0.08, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.2, 2.5, 2.8, 3.0, 3.2, 3.5, 3.8, 4.0, 4.2, 4.5, 4.8, or 5.0, or a value within a range between any of the preceding values, e.g., between about 0.08 wt% and about 2.5 wt%, or the like.

[0048] In many embodiments the betaine compound and the water may be present in a weight ratio of about 1: 120 to about 1:5. For example, the betaine compound and the water may be present in a weight ratio of about 1:5000, 1:4500, 1:4000, 1 :3500, 1:3000, 1:2500, 1:2000, 1:1500, 1: 1000, 1:500, 1: 100, 1:50, 1 :1, or 1:5, or a value within a range between any of the preceding values, e.g., between 1:5000 and about 1 : 100, or the like. Too much water or too little betaine compound, when an organic thickener is present, can result in an unstable composition that phase separates.

[0049] In some embodiments, the betaine compound and the source of calcium ions may be present in a weight ratio of about 120: 1 to about 2: 1. For example, the betaine compound and the source of calcium ions may be present in a weight ratio of about 120: 1, 100: 1, 80: 1, 50:1, 20: 1, 15: 1, 10: 1, 9: 1, 8: 1, 7: 1, 6: 1, 5: 1, 4: 1, 3: 1, or 2: 1, or a value within a range between any of the preceding values, e.g., between 5: 1 to 3: 1, or the like. Too many calcium ions or too little betaine compound can result in precipitation of insoluble calcium salts.

[0050] For oral care compositions having a thickening silica, the betaine compound and the thickening silica may be present in weight ratio of about 0.01 : 1 to about 0.4: 1. For example, the betaine compound and the amorphous silica may be present in a weight ratio of about 0.01: 1, 0.05:1, 0.1: 1, 0.12: 1, 0.15: 1, 0.18: 1, 0.2:1, 0.22:1, 0.25:1, 0.28: 1, 0.3: 1, 0.32: 1, 0.35: 1, 0.38:1, or 0.4:1, or a value within a range between any of the preceding values, e.g., between about 0.04: 1 to 0.2: 1, or the like.

[0051] For oral care compositions having an abrasive agent, the betaine compound and the abrasive agent may be present in a weight ratio of about 0.02: 1 to about 0.4: 1. For example, the betaine compound and the abrasive agent may be present in a weight ratio of about 0.2: 1, 0.22: 1, 0.25 : 1, 0.28: 1, 0.3: 1, 0.32:1, 0.35: 1, 0.38: 1, or 0.4: l„ or a value within a range between any of the preceding values, e.g., between about 0.025: 1 to 0.35:1, or the like.Source of fluoride ions

[0052] The oral care compositions of the present disclosure may include one or more sources of fluoride ions.

[0053] In some embodiments, the source of fluoride ions may be characterized by a water solubility of at least 1 g per liter of water at 20 °C. In some embodiments, the source of fluoride ions may be characterized by a water solubility of about 0.1 wt% to about 50 wt% in water.

[0054] In some embodiments, the source of fluoride ions may include or be an inorganic compound. Example inorganic fluoride ion sources include, but is not limited to, sodium fluoride, potassium fluoride, magnesium fluoride, sodium monofluorophosphate, stannous fluoride, strontium fluoride, zinc fluoride, zinc potassium fluoride, ammonium fluoride, ammonium tetrafluoroborate, and a combination thereof. In some embodiments, the source of fluoride ions may be sodium fluoride and only sodium fluoride.

[0055] In some embodiments, the source of fluoride ions may include or be an organic compound. Example organic fluoride ion sources include, but is not limited to, quaternary ammonium fluoride compounds. For example, the source of fluoride ions may be represented by Formula I:(R1)4-N+X- (I), wherein: each R1may be independently selected from a C1-12 straight or branched alkyl and a C7-12 straight or branched alkaryl or alkaralkyl; and X may be F or BF4. In some embodiments, the source of fluoride ions may include or be selected from tetrabutylammonium fluoride, tetrabutylammonium tetrafluoroborate, and a combination thereof. Protonated amino fluoride compounds are also suitable organic fluoride ion sources, e.g., protonated trialkylamine fluorides or protonated trialkanolamine fluorides.

[0056] In some embodiments, the source of fluoride ions and the source of calcium ions together may be provided as a chelating complex, i.e., calcium ions and fluoride ions are complexed by a chelator compound. In many embodiments, a chelator compound may be characterized by an ability to form a 5-, 6-, or 7-membered metallacycle with calcium. This does not necessarily mean that metallacycles do form under all conditions. In other words, a chelator compound may possess at least two functional groups having a heteroatom wherein the heteroatoms are separated by 2, 3, or 4 atoms. Suitable functional groups include, for example, -OH, -C(O)OH, and -P(O)(OH)2 (or the corresponding conjugate bases, i.e., deprotonated groups). In some embodiments, a chelator compound may include at least two -C(O)OH or at least two -P(O)(OH)2(or the corresponding conjugate bases), wherein the heteroatoms are separated by 2, 3, or 4 atoms. In some embodiments, a chelator compound of the chelating complex may be characterized by one or more of: a molecular weight of less than 300 g / mol and a water solubility of at least 1 g per liter water at 20 °C. Example chelator compounds include, but not limited to, citrate and etidronate. In some embodiments, the chelating complex may be a calcium citrate fluoride complex, such as those described in Int. Pat. Pub. No. WO 2023 / 194819, incorporated herein by reference in its entirety. In some embodiments, a calcium citrate fluoride complex may be characterized by having at least 2 mole chelator compound (e.g., citrate) for every 3 mole calcium and at least 1 mole of fluoride for every 1 mole calcium. In some embodiments, a chelating complex may be present in an amount of about 0.01 wt% to about 2.0 wt% with respect to the weight of the oral care composition. For example, a chelating complex may be present in an amount (wt%) of about 0.01, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0, or avalue within a range between any of the preceding values, e.g., between about 0.1 wt% and about 1.0 wt%, or the like.

[0057] In some embodiments, the source of fluoride ions may be present in a total amount of about0.1 wt% to about 3 wt% with respect to the weight of the oral care composition. For example, the source of fluoride ions may be present in an amount, in wt%, of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3, or a value within a range between any of the preceding values, e.g., between about 1.5 wt% and about 3 wt%, or the like.

[0058] In some embodiments, the source of fluoride ions may provide fluoride ions in an amount of about 0.04 wt% to about 1.2 wt% with respect to the weight of the oral care composition. For example, fluoride ions may be present in an amount (wt%) of about 0.04, 0.05, 0.1, 0.15, 0.2, 2.5, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0, 1.05, 1.1, 1.15, or 1.2, or avalue within a range between any of the preceding values, e.g., between about 0.4 wt% to 1 wt%, or the like.Source of calcium ions

[0059] The oral care compositions of the present disclosure may include one or more sources of calcium ions.

[0060] In some embodiments, the source of calcium ions may be characterized by a water solubility of at least 1 g per liter of water at 20 °C. In some embodiments, the source of calcium ions may be characterized by a water solubility of about 1 wt% to about 50 wt% in water.

[0061] In some embodiments, the source of calcium ions may include or be an inorganic compound. Example inorganic calcium ion sources include, but is not limited to, calcium chloride, calcium nitrate, calcium sulfate, calcium dihydrogen phosphate, calcium hydrogen sulfate, calcium hydroxide, and a combination thereof.

[0062] In some embodiments, the source of calcium ions may include or be an organic compound. Example organic calcium ion sources include, but is not limited to, calcium gluconate, calcium lactate, calcium lactate gluconate, calcium acetate, calcium citrate, calcium itaconate, and a combination thereof.

[0063] In some embodiments, the source of calcium ions may be a chelated calcium compound, such as the example organic calcium ion sources listed above. In other embodiments, the source of calcium ions may include or be an inorganic compound, such as the inorganic calcium ion sources listed above, yet the composition may further include an chelating compound (e.g., citric acid / citrate, gluconic acid / gluconate, or the like) that may form a chelated calcium compound in situ, e.g., calcium hydroxide and citric acid, calcium chloride and citric acid, or the like.

[0064] In some embodiments, the source of calcium ions may be present in a total amount of about0.01 wt% to about 2.0 wt% with respect to the weight of the oral care composition. For example, thesource of calcium ions may be present in total amount (wt%) of about 0.01, 0.025, 0.045, 0.05, 0.0.0.75, 0.1, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0, or avalue within a range between any of the preceding values, e.g., between about 0.045 wt% and about 1.0 wt%, or the like. In many embodiments, calcium ions may be present in a total amount of about 0.002 wt% to about 0.5 wt% with respect to the weight of the oral care composition. For example, calcium ions may be present in a total amount (wt%) of about 0.002, 0.003, 0.004, 0.005, 0.01, 0.025, 0.05, 0.075, 0.1, 0.125, 0.150, 0.175, 0.2, 0.225, 0.250, 0.275, 0.3, 0.325, 0.350, 0.375, 0.4, 0.425, 0.450, 0.475, or 0.5, or a value within a range between any of the preceding values, e.g., between about 0.2 wt% and about 0.4 wt%, or the like.

[0065] In some embodiments, the source of calcium ions and the water may be present in weight ratio of about 1: 10 to about 1:2000. For example, the source of calcium ions and the water may be present in a weight ratio of about 1: 10, 1:25, 1:50, 1:75, 1: 100, 1: 150, 1:200, 1:250, 1:300, 1:350, 1:400, 1:450, 1:500, 1:600, 1:700, 1:800, 1:900, 1: 1000, 1: 1100, 1: 1200, 1:1300, 1 :1400, 1: 1500, 1 : 1600, 1 : 1700, 1 : 1800, 1 : 1900, or 1 :2000, or a value within a range between any of the preceding values, e.g., between about 1:50 and about 1: 1000, or the like.Source of Phosphate Ions

[0066] The oral care compositions of the present disclosure may further include one or more sources of phosphate ions.

[0067] In some embodiments, the source of phosphate ions may be characterized by a water solubility of at least 1 g per liter of water at 20 °C. In some embodiments, the source of phosphate ions may be characterized by a water solubility of about 1 wt% to 45 wt% in water.

[0068] Example sources of phosphate ions may include, but not limited to, sodium phosphate, disodium phosphate, sodium biphosphate, sodium triphosphate, potassium phosphate, potassium biphosphate, potassium triphosphate, sodium potassium phosphate, ammonium hydrogen phosphate, tripotassium phosphate, potassium dihydrogen phosphate, and a combination thereof.

[0069] In some embodiments, the source of phosphate ions, if present, may be present in a total amount of about 0.01 wt% to about 5 wt% with respect to the weight of the oral care composition. For example, the source of calcium ions may be present in total amount (wt%) of about 0.01, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.2, 1.5, 1.8, 2, 2.2, 2.5, 2.8, 3, 3.2, 3.5, 3.8, 4, 4.2, 4.5, 4.8, or 5, or a value within a range between any of the preceding values, e.g., between about 0.05 wt% and about 1.0 wt%, or the like.

[0070] In some embodiments, the source of phosphate ions, if present, may be present in an amount to provide phosphate ions in an amount of about 0.005 wt% to about 3.5 wt%. For example, phosphate ions may be present in an amount (wt%) of about 0.005, 0.01, 0.05, 0.1, 0.5, 1, 1.5, 2.0, 2.5, 3.0, or 3.5,or a value within a range between any of the preceding values, e.g., between about 0.1 and about 1, or the like.

[0071] In some embodiments, the source of phosphate ions and the calcium ions may be present in a weight ratio of about 0.05: 1 to about 100:1. For example, the source of phosphate ions and the source of calcium ions may be present in a weight ratio of about 0.05: 1, 0.5: 1, 1: 1, 1.5:1, 2: 1, 3: 1, 4: 1, 5: 1, 10: 1, 15: 1, 20: 1, 25: 1, 30:1, 35:1, 40: 1, 45: 1, 50: 1, 60: 1, 70:1, 80: 1, 90: 1, or 100: 1, or a value within a range between any of the preceding values, e.g., between about 0.05: 1 and about 50: 1, or the like.Thickening silica

[0072] In some embodiments, the thickening silica may be characterized by a mean particle size of no greater than 50 micron. For example, the thickening silica may be characterized by a mean particles size of about 1 micron to about 30 micron.

[0073] In some embodiments, the thickening silica may be or may be selected from diatomaceous earth, precipitated amorphous silica, amorphous silica gel, pyrogenic silica, fumed amorphous silica, fused amorphous silica, colloidal amorphous silica, and a combination thereof.

[0074] In some embodiments, the thickening silica may be present in an amount of about 1 wt% to about 10 wt% with respect to the weight of the oral care composition. For example, the thickening silica may be present in total amount (wt%) of about 1, 1.2, 1.5, 1.8, 2, 2.2, 2.5, 2.8, 3, 3.2, 3.5, 3.8, 4,4.2, 4.5, 4.8, 5, 5.2, 5.5, 5.8, 6, 6.2, 6.5, 6.8, 7, 7.2, 7.5, 7.8, 8, 8.2, 8.5, 8.8, 9, 9.2, 9.5, 9.8, or 10, or a value within a range between any of the preceding values, e.g., between about 2 wt% and about 8 wt%, or the like.

[0075] In some embodiments, the thickening silica and the abrasive agent may be present in a weight ratio of 1:0.1 to about 1:5. For example, the thickening silica and the abrasive agent may be present in a weight ratio of about 1 :0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1 :0.9, 1: 1, 1.1, 1.2,1.3, 1.4, or 1.5, or a value within a range between any of the preceding values, e.g., between about 1: 1 and about 1:3, or the like.Abrasive agent

[0076] The abrasive agents of the present disclosure impart cleaning action upon contact with tooth structures.

[0077] In some embodiments, the abrasive agent may be characterized by mean particle size of 1 to 70 micron. In some embodiments, the mean particle size may be greater than 30 micron and less than 70 micron.

[0078] In some embodiments, the abrasive agent may be or may be selected from silica, silica gel, hydrated silica precipitated silica, fused silica, alumina, calcined alumina, insoluble phosphates (e.g., orthophosphates, polymetaphosphates, pyrophosphates, e.g., dicalcium orthophosphate dihydrate,dicalcium phosphate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate, hydroxyapatite, magnesium orthophosphate, sodium polymetaphosphate), calcium carbonate, ground glass, silicon carbide, ilmenite, sodium bicarbonate, bentonite, mica, zirconia, zirconia silicate, topaz, titanium dioxide, precipitated lime, chalk, pumice, zeolites, talcum, kaolin, diatomaceous earth, silicates, resinous abrasives (e.g., urea-formaldehyde condensation products), or a combination thereof.

[0079] In some embodiments, the abrasive agent may be present in an amount of about 1 wt% to about 30 wt% with respect to the weight of the oral care composition. For example, the abrasive agent may be present in total amount (wt%) of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30, or a value within a range between any of the preceding values, e.g., between about 8 wt% and about 18 wt%, or the like.

[0080] In some embodiments, the abrasive agent and the water being present in a weight ratio of about 1:2 to about 1:5. For example, the abrasive agent and the water may be present in a weight ratio of about 1:2, 1:2.2, 1 :2.5, 1:2.8, 1:3, 1:3.2, 1:3.5, 1:3.8, 1 :4, 1:4.2, 1:4.5, 1:4.8, or 1:5, or a value within a range between any of the preceding values, e.g., between about 1:2.5 and about 1:4., or the like.Water

[0081] In some embodiments, the water may be present in an amount of about 20 wt% to about 70 wt% with respect to the weight of the oral care composition. For example, the water may be present in total amount (wt%) of about 20, 22, 25, 28, 30, 32, 35, 38, 40, 42, 45, 48, 50, 52, 55, 58, 60, 62, 65, 68, or 70, or a value within a range between any of the preceding values, e.g., between about 30 wt% and about 55 wt%, or the like.Organic Thickeners

[0082] The oral care compositions of the present disclosure may optionally further include one or more thickening agent that is an organic compound.

[0083] In some embodiments, the organic thickener may be, or may include, a polymer containing hydroxyl group(s), e.g., ethyl hydroxyl side group(s), propyl hydroxyl side group(s), or a combination thereof.

[0084] In some embodiments, the organic thickener may be or include a polysaccharide thickener. Any suitable polysaccharide thickener may be characterized as being without acidic groups (e.g., carboxylic acids, phosphonic acids, sulfonic acid, or the like) or groups corresponding to a conjugate base (e.g., carboxylates, phosphonates, sulfonates, or the like), i.e., a non-acidic or non-acid conjugate polysaccharide. Thus, polysaccharide thickeners having acidic or conjugate acid groups, such as xanthan gum and carboxymethyl cellulose, may be excluded from the oral care compositions. Thickeners such as xanthan gum and carboxymethyl cellulose were observed to cause phase separation.

[0085] In some embodiments, the organic thickener may include or may be selected from hydroxyethyl cellulose, guar gum, hydroxypropyl cellulose, polyvinyl alcohol,poly(hydroxyethyl)methacrylate (“polyHEMA”), poly(hydroxyethyl)acrylate (“PolyHEA”), or a combination thereof.

[0086] In other embodiments, the organic thickener may be or include one or more alkylene oxide polymer (e.g., polyethylene glycol, polypropylene glycol, and copolymers of polyethylene glycol and polypropylene glycol).

[0087] In some embodiments, an organic thickener may be present in an amount of about 0.1 wt% to about 2.5 wt% with respect to the weight of the oral care composition. For example, the organic thickener may be present in an amount (wt%) of about 0.1, 0.2, 0.5, 0.8, 1, 1.2, 1.5, 1.8, 2, 2.2, or 2.5, or a value within a range between any of the preceding values, e.g., between about 0.2 wt% and about 2 wt%, between about 0.5 wt% and about 2 wt%, or the like.

[0088] In some embodiments, an organic thickener and the betaine compound may be present in a weight ratio of about 1:4 to about 1:0.25. For example, the organic thickener and the betaine compound may be present in a weight ratio of about 1:4, 1:3.8, 1:3.5, 1:3.2, 1:3, 1:2.8, 1:2.5, 1:2.2, 1:2, 1:1.8, 1:1.5, 1: 1.2, 1:1, 1:0.9, 1:0.8, 1:0.7, 1:0.6, 1:0.5, 1:0.4, 1:0.3, or 1:0.25, or a value within a range between any of the preceding values, e.g., between about 1:3 and about 1:0.3, or the like.

[0089] In some embodiments, an organic thickener and the water may be present in a weight ratio of about 1:200 to about 1:20. For example, the organic thickener and the water ions may be present in a weight ratio of about 1:200, 1:190, 1:180, 1:170, 1:160, 1:150, 1:140, 1:130, 1:120, 1:110, 1:100, 1:90, 1:80, 1:70, 1:60, 1:50, 1:40, 1:30, or 1:20, or a value within a range between any of the preceding values, e.g., between about 1:100 to 1:30, orthe like.Chelator Compound

[0090] In some embodiments, the oral care composition may further include a chelator compound. As discussed above, a chelator compound may be characterized by an ability to form a 5-, 6-, or 7- membered metallacycle with calcium. This does not necessarily mean that metallacycles do form under all conditions. In other words, a chelator compound may possess at least two functional groups having a heteroatom wherein the heteroatoms are separated by 2, 3, or 4 atoms. Suitable functional groups include, for example, -OH, -C(O)OH, and -P(O)(OH)2 (or the corresponding conjugate bases, i.e., deprotonated groups). In some embodiments, a chelator compound may include at least two -C(O)OH or at least two -P(O)(OH)2(or the corresponding conjugate bases), wherein the heteroatoms are separated by 2, 3, or 4 atoms. In some embodiments, a chelator compound of the chelating complex may be characterized by one or more of: a molecular weight of less than 300 g / mol and a water solubility of at least 1 g per liter water at 20 °C. Example chelator compounds include, but not limited to, citrate and etidronate.

[0091] In some embodiments, the chelator compound may be present in an amount of about 0.01 wt% to about 0.5 wt% with respect to the weight of the oral care composition. For example, any oralcare composition herein may further include a chelator compound (e.g., a citrate such as sodium citrate, citric acid, or combination thereof) in an amount (wt%) of about 0.01, 0.02, 0.05, 0.08, 0.1, 0.12, 0.15, 0.18, 0.2, 0.22, 0.25, 0.28, 0.3, 0.32, 0.35, 0.38, 0.4, 0.42, 0.45, 0.48, or 0.5, or a value within a range between any of the preceding values, e.g., between about 0.1 wt% and about 0.2 wt%, or the like.

[0092] In some embodiments, a chelator compound may be present in an amount such that there may be least 2 mole chelator compound (e.g., citrate) for every 3 mole calcium. In some embodiments, a chelator compound may be present in an amount such that there may be at least 2 mole chelator compound for every 1 mole of fluoride.Other Additives

[0093] In many embodiments, the oral care composition may optionally further include one or more optional additives, such as a buffering agent, a sweetener, a flavoring agent, a desensitizing agent, a whitening agent, an anti-calculus agent, an antimicrobial agent a saliva-stimulating agent, a breathfreshening agent, an antioxidant, an anti-inflammatory agent, and a histamine H2antagonist. In other embodiments, the oral care composition may exclude one or more of the aforementioned classes or exclude one or more of the following specific components.

[0094] Example buffering agents include, but not limited to, triethanolamine, citrate buffer, phosphate buffer, acetate buffer, or the like. In some embodiments, buffering agents may be present in an amount of about 0.1 wt% to about 10 wt% with respect to the weight of the oral care composition, e.g., 0.1, 0.5, 1, 2, 5, 8, or 10 wt%, or a value within a range between any of the preceding values.

[0095] Example sweeteners include, but not limited to, xylitol, sucrose, glucose syrup, aspartame, sucralose, and other known artificial sweeteners. In some embodiments, sweetener(s) may be present in an amount of about 0.5 wt-% to 15 wt-% with respect to the weight of the oral care composition. For example, sweetener(s) may be present in an amount (wt% with respect to the weight of the oral care composition) of about 0.5, 1, 2, 5, 8, 10, 12, or 15, or a value within a range between any ofthe preceding values, e.g., between about 2 wt% and about 5 wt%, or the like.

[0096] Example flavoring agents include, but not limited to, peppermint oil, spearmint oil, cherry flavor, orange flavor, vanilla, strawberry flavor, coconut flavor, and bubble gum flavor. In some embodiments, flavoring agent(s) may be present in an amount of about 1 wt-% to 4 wt-%, with respect to the weight of the oral care composition. For example, flavoring agent(s) may be present in an amount (wt%) of about 1, 1.5, 2, 2.5, 3, 3.5, or 4, or a value within a range between any ofthe preceding values, e.g., between about 1 wt% and about 3.5 wt%, or the like.

[0097] Example desensitizing agents include, but is not limited to, potassium nitrate. In some embodiments, desensitizing agent(s) may be present in an amount of about 1 wt% to about 8 wt% with respect to the weight of the oral care composition. For example, desensitizing agent(s) may be presentin an amount (wt%) of about 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8, or a value within a range between any of the preceding values, e.g., between about 2 wt% and about 3 wt%.

[0098] Example whitening agents include, but not limited to, peroxides such as hydrogen peroxide, alkali or alkaline earth peroxides, and organic peroxides such as benzoyl peroxide or peroxy acids; and non-peroxides such chlorine dioxide, chlorites, and hypochlorites.

[0099] Example anti-calculus include, but is not limited to, pyrophosphates, polyolefin sulfonates, polyolefin phosphates, diphosphonates, and phosphonoalkane carboxylic acids.

[0100] Example antimicrobial agents, include, but not limited to, triclosan, 8-hydroxyquinoline, zinc or stannous ions, cupric compounds, phthalic acid and salts thereof, quaternary ammonium compounds, sanguinarine, salicylanilide, salicylic acid, thymol, eugenol, neomycin, kanamycin, clindamycin, amoxicillin, tetracycline, doxycycline, minocycline, metronidazole, and chlorohexidine.

[0101] Example saliva-stimulating agents include, but not limited to, citric acid, lactic acid, succinic acid, ascorbic acid, adipic acid, fumaric acid, and tartaric acid.

[0102] Example breath-freshening agents include, but not limited to, zinc salts such as zinc gluconate, zinc citrate, zinc chlorite, and alpha-ionone.

[0103] Example anti-oxidants include, but not limited to, butylated hydroxy anisole, butylated hydroxy toluene, vitamin A, carotenoids, vitamin E, flavonoids, polyphenols, ascorbic acid or salts thereof, chlorophyll, and melatonin.

[0104] Example anti-inflammatory agents include, but not limited to, fluocinolone, hydrocortisone, ketorolac, flurbiprofen, ibuprofen, naproxen, indomethacin, diclofenac, etodolac, indomethacin, sulindac, tolmetin, ketoprofen, fenoprofen, piroxicam, nabumetone, acetyl salicylic acid, salicylic acid, diflunisal, meclofenamate, mefenamic acid oxyphenbutazone, and phenylbutazone.

[0105] Example histamine H2antagonists include, but not limited to, cimetidine, ranitidine, tiotidine, lupitidine, famotidine, roxatidine, lamtidine, zaltidine, nizatidine, mifentidine, lavoltidine, bisfentidine, sufotidine, ebrotidine, and impromidine.Solution Compositions

[0106] In some embodiments, the oral care composition may include, may consist essentially of, or may consist only of, the following: a betaine compound represented by Formula I (e.g., Formula la, lb, or combination thereof) present in an amount of about 0.025 wt% to about 5 wt%; a source of fluoride ions (e.g., sodium fluoride) present in an amount of about 0.1 wt% to about 2.5 wt%, or a source of fluoride ions present in an amount to provide fluoride ions in an amount of about 0.04 wt% to about 1.2 wt%;a source of calcium ions (e.g., calcium citrate) present in an amount of about 0.01 wt% to about 2 wt%, or a source of calcium ions present in an amount to provide calcium ions in an amount of about 0.002 wt% to about 0.5 wt%; and water present in an amount of about 20 wt% to about 70 wt%.

[0107] In some embodiments, the oral care composition may include, may consist essentially of, or may consist only of, the following: a betaine compound represented by Formula I (e.g., Formula la, lb, or combination thereof) present in an amount of about 0.025 wt% to about 2 wt%; a source of fluoride ions (e.g., sodium fluoride) present in an amount of about 0.1 wt% to about 2.5 wt%, or a source of fluoride ions present in an amount to provide fluoride ions in an amount of about 0.04 wt% to about 1.2 wt%; a source of calcium ions (e.g., calcium citrate) present in an amount of about 0.01 wt% to about 2 wt%, or a source of calcium ions present in an amount to provide calcium ions in an amount of about 0.002 wt% to about 0.5 wt%; a source of phosphate ions (e.g., sodium hydrogen phosphate) present in an amount of about 0.01 wt% to about 5 wt%, or a source of phosphate ions present in an amount to provide phosphate ions in an amount of about 0.006 wt% to about 3.35 wt%; and water present in an amount of about 20 wt% to about 70 wt%.

[0108] Solutions may be free of precipitates. Solutions may be free of calcium fluoride and calcium phosphate precipitates.

[0109] Solutions can be used as a mouthwash or rinse for remineralizing teeth.

[0110] Solutions may be further combined with one or more of: organic thickeners, silica thickeners, and abrasive agents to form colloid compositions or paste compositions.[oni] Solutions may further include additives described herein (e.g., flavor, sweetener, or the like). Any such additive may be present in a collective amount (i.e., total additives) of about 0 wt% to about 4 wt% with respect to the weight of the oral care composition.Colloid Compositions

[0112] In some embodiments, the oral care composition may include, may consist essentially of, or may consist only of, the following: a betaine compound represented by Formula I (e.g., Formula la, lb, or combination thereof) present in an amount of about 0.025 wt% to about 5 wt%; a source of fluoride ions (e.g., sodium fluoride) present in an amount of about 0.1 wt% to about 2.5 wt%, or a source of fluoride ions present in an amount to provide fluoride ions in an amount of about 0.04 wt% to about 1.2 wt%;a source of calcium ions (e.g., calcium citrate) present in an amount of about 0.01 wt% to about 2 wt%, or a source of calcium ions present in an amount to provide calcium ions in an amount of about 0.002 wt% to about 0.5 wt%; an organic thickener (e.g., a non-acidic, non-acid-conjugate polysaccharide thickener, e.g., hydroxy ethyl cellulose) present in an amount of about 0.1 wt% to about 2.5 wt%; and water present in an amount of about 20 wt% to about 70 wt%.

[0113] In some embodiments, the oral care composition may include, may consist essentially of, or may consist only of, the following: a betaine compound represented by Formula I (e.g., Formula la, lb, or combination thereof) present in an amount of about 0.025 wt% to about 5 wt%; a source of fluoride ions (e.g., sodium fluoride) present in an amount of about 0.1 wt% to about 2.5 wt%, or a source of fluoride ions present in an amount to provide fluoride ions in an amount of about 0.04 wt% to about 1.2 wt%; a source of calcium ions (e.g., calcium citrate) present in an amount of about 0.01 wt% to about 2 wt%, or a source of calcium ions present in an amount to provide calcium ions in an amount of about 0.002 wt% to about 0.5 wt%; a source of phosphate ions (e.g., sodium hydrogen phosphate) present in an amount of about 0.01 wt% to about 5 wt%, or a source of phosphate ions present in an amount to provide phosphate ions in an amount of about 0.006 wt% to about 3.35 wt%; an organic thickener (e.g., a non-acidic, non-acid-conjugate polysaccharide thickener, e.g., hydroxy ethyl cellulose) present in an amount of about 0.1 wt% to about 2.5 wt%; and water present in an amount of about 20 wt% to about 70 wt%.

[0114] Colloid compositions may be free of precipitates and uniformly phase stable. Colloid compositions may be free of calcium fluoride and calcium phosphate precipitates and uniformly phase stable.

[0115] Colloid compositions may be used as a remineralizing gel treatment.

[0116] Colloid composition may be further combined with one or more of silica thickeners and abrasive agents to form a paste composition.

[0117] Colloid compositions may further include additives described herein (e.g., flavor, sweetener, or the like). Any such additive may be present in a collective amount (i.e., total additives) of 0 wt% to about 4 wt% with respect to the weight of the oral care composition.

[0118] Colloid compositions may further include one or more water-soluble polymers for use as a varnish.Paste Compositions

[0119] In some embodiments, the oral care composition may include, may consist essentially of, or may consist only of, the following: a betaine compound represented by Formula I (e.g., Formula la, lb, or combination thereof) present in an amount of about 0.025 wt% to about 5 wt%; a source of fluoride ions (e.g., sodium fluoride) present in an amount of about 0.1 wt% to about 2.5 wt%, or a source of fluoride ions present in an amount to provide fluoride ions in an amount of about 0.04 wt% to about 1.2 wt%; a source of calcium ions (e.g., calcium citrate) present in an amount of about 0.01 wt% to about 2 wt%, or a source of calcium ions present in an amount to provide calcium ions in an amount of about 0.002 wt% to about 0.5 wt%; water present in an amount of about 20 wt% to about 70 wt%; silica as a thickening agent present in an amount of about 1 wt% to about 10 wt%; and an abrasive agent present in an amount of about 5 wt% to about 20 wt%.

[0120] In some embodiments, the oral care composition may include, may consist essentially of, or may consist only of, the following: a betaine compound represented by Formula I (e.g., Formula la, lb, or combination thereof) present in an amount of about 0.025 wt% to about 5 wt%; a source of fluoride ions (e.g., sodium fluoride) present in an amount of about 0.1 wt% to about 2.5 wt%, or a source of fluoride ions present in an amount to provide fluoride ions in an amount of about 0.04 wt% to about 1.2 wt%; a source of calcium ions (e.g., calcium citrate) present in an amount of about 0.01 wt% to about 2 wt%, or a source of calcium ions present in an amount to provide calcium ions in an amount of about 0.002 wt% to about 0.5 wt%; a source of phosphate ions (e.g., sodium hydrogen phosphate) present in an amount of about 0.01 wt% to about 5 wt%, or a source of phosphate ions present in an amount to provide phosphate ions in an amount of about 0.006 wt% to about 3.35 wt%; water present in an amount of about 20 wt% to about 70 wt%; silica as a thickening agent present in an amount of about 1 wt% to about 10 wt%; and an abrasive agent present in an amount of about 5 wt% to about 20 wt%.

[0121] In some embodiments, the oral care composition may include, may consist essentially of, or may consist only of, the following: a betaine compound represented by Formula I (e.g., Formula la, lb, or combination thereof) present in an amount of about 0.025 wt% to about 5 wt%;a source of fluoride ions (e.g., sodium fluoride) present in an amount of about 0.1 wt% to about 2.5 wt%, or a source of fluoride ions present in an amount to provide fluoride ions in an amount of about 0.04 wt% to about 1.2 wt%; a source of calcium ions (e.g., calcium citrate) present in an amount of about 0.01 wt% to about 2 wt%, or a source of calcium ions present in an amount to provide calcium ions in an amount of about 0.002 wt% to about 0.5 wt%; an organic thickener (e.g., a non-acidic, non-acid-conjugate polysaccharide thickener, e.g., hydroxy ethyl cellulose) present in an amount of about 0.1 wt% to about 2.5 wt%; water present in an amount of about 20 wt% to about 70 wt%; silica as a thickening agent present in an amount of about 1 wt% to about 10 wt%; and an abrasive agent present in an amount of about 5 wt% to about 20 wt%.

[0122] In some embodiments, the oral care composition may include, may consist essentially of, or may consist only of, the following: a betaine compound represented by Formula I (e.g., Formula la, lb, or combination thereof) present in an amount of about 0.025 wt% to about 5 wt%; a source of fluoride ions (e.g., sodium fluoride) present in an amount of about 0.1 wt% to about 2.5 wt%, or a source of fluoride ions present in an amount to provide fluoride ions in an amount of about 0.04 wt% to about 1.2 wt%; a source of calcium ions (e.g., calcium citrate) present in an amount of about 0.01 wt% to about 2 wt%, or a source of calcium ions present in an amount to provide calcium ions in an amount of about 0.002 wt% to about 0.5 wt%; a source of phosphate ions (e.g., sodium hydrogen phosphate) present in an amount of about 0.01 wt% to about 5 wt%, or a source of phosphate ions present in an amount to provide phosphate ions in an amount of about 0.006 wt% to about 3.35 wt%; an organic thickener (e.g., a non-acidic, non-acid-conjugate polysaccharide thickener, e.g., hydroxy ethyl cellulose) present in an amount of about 0.1 wt% to about 2.5 wt%; water present in an amount of about 20 wt% to about 70 wt%; silica as a thickening agent present in an amount of about 1 wt% to about 10 wt%; and an abrasive agent present in an amount of about 5 wt% to about 20 wt%.

[0123] Paste compositions may be free of calcium fluoride and calcium phosphate precipitates and uniformly phase stable.

[0124] Paste compositions may be used as a toothpaste.

[0125] Paste compositions may further include additives described herein (e.g., flavor, sweetener, or the like). Any such additive may be present in a collective amount (i.e., total additives) of 0 wt% to about 4 wt% with respect to the weight of the oral care composition.METHODS FOR PREPARING ORAL CARE COMPOSITIONS

[0126] In various embodiments, a method for preparing an oral care composition of the present disclosure is described. The method may include providing the following: a betaine compound of Formula I, a source of fluoride ions, a source of calcium ions, a source of phosphate ions, and water. The method may further include combining and mixing the aforementioned components to form the oral care composition.

[0127] In various embodiments, a method for preparing an oral care composition of the present disclosure is described. The method may include providing the following: a betaine compound of Formula I, a source of fluoride ions, a source of calcium ions, a source of phosphate ions, silica as a thickening agent, an abrasive agent, and water. The method may further include combining and mixing the aforementioned components to form the oral care composition.METHODS OF TREATMENT

[0128] In various embodiments, a method of treating a tooth surface is described. The method may include contacting an oral care composition of the present disclosure to the tooth surface.

[0129] In various embodiments, a method of cleaning and remineralizing a tooth surface is described. The method may include contacting an oral care composition of the present disclosure to the tooth surface.

[0130] In many embodiments, the methods may further include brushing or otherwise scrubbing the tooth surface having the oral care composition thereon.KITS

[0131] In various embodiments, a kit is described. The kit may include an oral care composition of the present disclosure and a set of instructions directing a user to contact the oral care composition to a tooth surface.EXAMPLESMethodsFluoride Release TestPreparatory Solutions

[0132] Fluoride release was measured on a Mettler Toledo T70 titrator. The Cole Parmer fluoride electrode was first calibrated with parts per million (ppm) fluoride standards with TISAB III before measuring samples for fluoride release each day (Total Ionic Strength Adjustment Buffer (TISAB) III concentrate solution is for use with fluoride ion selective electrodes, Sigma Aldrich). Each Example composition was coated inathinlayeronRINZL Plastic microscope slide with2.54 centimeters’ square area for both sides of the slide. The total weight of coating was about 0.045 gram. The fluoride meter titrator cup was filled with 50 milliliters of a mixture of 45 mL of MilliQ DI water and 5 mL TISAB III concentrate. The fluoride ion selective electrode was placed in the titrator cup of diluted TISAB III solution and allowed to equilibrate the meter for 30 seconds before analyzing each sample. After 30 seconds, the clamped sample was lowered into the 50 milliliters of diluted TISAB III solution. Fluoride release (mV) was measured at different time points during a 30-minute titration with Mettler Toledo T70 titrator. The fluoride release was calculated against the fluoride standards calibration curve. The average of two titrations for each example was reported.Toothpastes

[0133] Toothpastes (about 1 gram) were mixed with 50 mL DI water with vigorous agitation of magnetic mixing bar for 1 h to disperse toothpaste in DI water and allow the release of ions into the aqueous solution. The resulting aqueous solution (5 mL) was mixed with a TISAB buffer solution (5 mL). The fluoride ion release potential was measured by a calibrated fluoride ion selective electrode (Fluoride selective electrode from Thermo Scientific) that was calibrated with 300 ppm, 200 ppm, 100 ppm, 20 ppm, and 10 ppm fluoride ion standards. The fluoride ion availability was calculated into ppm for the starting materials. The electrode measured the millivolts (mv) with the ion measurement meter (from Thermo Scientific, Orion meter) and the mv data were used to calculate the ppm in the product for 3 replicates. The fluoride ion release potential of Clinpro 5000 toothpaste was also measured with this method.Calcium Release Test

[0134] The toothpastes (about 1 gram) were mixed with 50 mL DI water with vigorous agitation of magnetic mixing bar for 1 h to disperse toothpaste in DI water and release the ions into the aqueous solution. The calcium ion release potential was measured by a calibrated calcium ion selective electrode method (Ca electrode from Thermo Scientific) and calculated into ppm for the starting materials. The electrode was calibrated with 0.4 ppm, 4 ppm, 40 ppm, and 400 ppm calcium ion standards. For eachsample, 200 microliters of Calcium ISA was added for every 10 mL of sample. The electrode measured the mv with the ion measurement meter (from Thermo Scientific, Orion meter)) and the mv data were used to calculate the ppm in the product for 3 replicates. The calcium ion release potential of Clinpro 5000 toothpaste was also measured with this method. pH Testing

[0135] pH testing was carried out on a standard pH meter after calibration. The pH meter was ACCUMET model 15 pH meter from Fisher Scientific. The measurement was performed by inserting the pH probe into the solution, waiting for 2 minutes and recording the pH value. pH values were listed in the example table.Materials TablePREPARATORY CALCIUM CHELATE FLUORIDE COMPLEX

[0136] Calcium ions and fluoride ions can co-exist within a chelate complex without forming precipitate upon dissolution in water. Said complex is also stable in the presence of phosphate ions, i.e., no calcium phosphate precipitate forms in aqueous solutions.

[0137] The general procedure for preparing a calcium chelate fluoride complex is as follows. A calcium compound (e.g., calcium hydroxide, calcium chloride, or the like) is dissolved in water, followed by the addition of a chelating agent (e.g., citric acid, etidronic acid, or the like) to form a solution. A fluoride compound (e.g., sodium fluoride, potassium fluoride, or the like) is then added. Stable complexes are formed when there is at least 2 mol of chelating agent for every 3 mol of calcium, and 1 mol of fluoride for every 1 mol of calcium. A solid complex is obtained upon removal of water. Further detail may be found in Int. Pat. Pub. No. WO 2023 / 194819, incorporated herein by reference in its entirety.COMPARATIVE EXAMPLES 1-6: TOOTHPASTES

[0138] Comparative Examples 1-6: the following were added, in the amounts listed in Table 1A, to a 100 g mixing cup: water, sorbitol, glycerin, PEG600, Pluronic F127, sodium saccharin, calcium citrate fluoride complex, betaine surfactant (i.e., capramidopropyl betaine and / or cocamidopropyl betaine) or sodium lauryl sulfate or sodium \ -cocoyl- \ -mcthvl taurate, carboxymethyl cellulose, sodium fluoride, potassium or sodium hydrogen phosphate, and silicas. The resulting mixtures were mixed overnight and then allowed to stand for 4 h. Comparative Examples 1-3, with SLS and / or SCMT and CMC, resulted in a cloudy solution (i.e., viscous gel separation) and particle precipitation. Comparative Examples 4-6, without SLS and / or SCMT, but with betaine and CMC, resulted in a cloudy solution (i.e., viscous gel separation) but with no precipitation. The viscous gel separation was attributed to the presence of CMC, whereas the precipitation was attributed to the SLS and SCMT.Table 1A. Comparative Example ToothpastesEXAMPLES 1-5: TOOTHPASTES

[0139] Examples 1-5: The following were added to 100 g speed-mixing cup, in the amounts listed in Table IB, and magnetically stirred for 2-3 min to form a clear, homogenous solution with some foam: water, sorbitol, xylitol, glycerin, sodium saccharin, citric acid, calcium hydroxide or calcium citrate fluoride complex, hydroxy ethyl cellulose, and capramidopropyl betaine. Sodium fluoride was then added and the solution was further mixed for 2-3 min. A source of phosphate (potassium hydrogen phosphate or sodium hydrogen phosphate) was then added and the solution was further mixed for 2-3 min. Finally, the silica thickening agent and silica abrasive agent were added and further mixed for 2- 3 min.Table IB. Example ToothpastesTable 2. Fluoride-Release Test

[0140] The data demonstrates that each of the example toothpastes release more fluoride than Clinpro™ 5000, despite having relatively the same amount of sodium fluoride present. It is speculated that the presence of surfactant (i.e., sodium lauryl sulfate) in Clinpro™ 5000 may inhibit fluoride release.Table 3. Calcium-Release Test

[0141] The data demonstrates that each of the example toothpastes releases a substantial amount of calcium ions, whereas Clinpro™ 5000 releases does not appear to calcium ions despite having tricalcium phosphate present. Tricalcium phosphate (“TCP”) is intended to form hydroxyapatite within tooth structures, i.e., to remineralize tooth structures. However, TCP has a very low water solubility; hence, the negligible calcium release observed. Furthermore, overtime the SLS in Clinpro™ degrades and some degradation products have been shown to prematurely convert TCP to hydroxyapatite, which is less useful for remineralization. EXAMPLES 6-12: SOLUTIONS (with or without organic thickener, no silicas)

[0142] Examples 6-12: The components of Table 1C were added to 100 g speed-mixing cup and magnetically stirred for 2-3 min to form a clear, homogenous solution with some foam. No precipitate was observed for any of the examples, and no phase separation was observed in the presence of organic thickener.EQUIVALENTSThose skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific embodiments described specifically herein. Such equivalents are intended to be encompassed in the scope of the following claims.

Claims

What is claimed is:

1. An oral care composition comprising: a betaine compound represented by Formula I: R1-C(O)-Y-R2-N+(R3)2-R4-C(O)-O- (I), wherein:R1is a Ce-Cis alkyl or a Ce-Cis alkenyl,Y is -O- or -N(R5)-,R2is a C2-C8 alkylene, each R3is independently a Ci-Ce alkyl,R4is a C1-C4 alkylene, and R5is -H or a C1-C4 alkyl, a source of fluoride ions; a source of calcium ions; and water, wherein the oral care composition is free of precipitates.

2. An oral care composition comprising: a betaine compound represented by Formula I:R1-C(O)-Y-R2-N+(R3)2-R4-C(O)-O- (I), wherein:R1is a Ce-Cis alkyl or a Ce-Cis alkenyl,Y is -O- or -N(R5)-,R2is a C2-Cs alkylene, each R3is independently a Ci-Ce alkyl,R4is a C1-C4 alkylene,R5is -H or a C1-C4 alkyl, and a source of fluoride ions; a source of calcium ions; water; a silica as a thickening agent; and an abrasive agent.

3. The oral care composition of any one of the preceding claims, wherein R1is a Ce-Cn alkyl.

4. The oral care composition of any one of the preceding claims, wherein Y is -N(R5)-.

5. The oral care composition of any one of the preceding claims, wherein R2is a C2-C4 alkylene.

6. The oral care composition of any one of the preceding claims, wherein each R3is methyl.

7. The oral care composition of any one of the preceding claims, wherein R4is methylene.

8. The oral care composition of any one of the preceding claims, the betaine compound represented by Formula la:(la).

9. The oral care composition of any one of the preceding claims, the betaine compound represented by Formula lb:(lb).

10. The oral care composition of any one of the preceding claims, the betaine compound being present in an amount of 0.05% wt% to about 5.0 wt% with respect to the weight of the oral care composition.

11. The oral care composition of any one of the preceding claims, the betaine compound and the water being present in a weight ratio of about 1 : 120 to about 1:5.

12. The oral care composition of any one of the preceding claims, the betaine compound and the source of calcium ions being present in a weight ratio of about 120: 1 to about 2: 1.

13. The oral care composition of any one of the preceding claims, the betaine compound and the silica as a thickening agent being present in a weight ratio of about O.Ol: ! to about 0.4:l.

14. The oral care composition of any one of the preceding claims, the betaine compound and the abrasive agent being present in a weight ratio of about 0.02:1 to about 0.4:1.

15. The oral care composition of any one of the preceding claims, the source of fluoride ions characterized by a water solubility of at least 1 g per liter of water at 20 °C.

16. The oral care composition of any one of the preceding claims, the source of fluoride ions comprising or being an inorganic compound.

17. The oral care composition of any one of the preceding claims, the source of fluoride ions comprising or being selected from sodium fluoride, potassium fluoride, magnesium fluoride, sodium monofluorophosphate, stannous fluoride, strontium fluoride, zinc fluoride, zinc potassium fluoride, ammonium fluoride, ammonium tetrafluoroborate, and a combination thereof.

18. The oral care composition of any one of the preceding claims, the source of fluoride ions being sodium fluoride.

19. The oral care composition of any one of the preceding claims, the source of fluoride ions comprising or being an organic compound.

20. The oral care composition of any one of the preceding claims, the source of fluoride ions comprising or being an organofluoride salt of Formula I:(R1)4-N+X- (I), wherein: each R1may be independently selected from a C1-12 straight or branched alkyl and a CT- 12 straight or branched alkaryl or alkaralkyl; and X may be F or BFi.

21. The oral care composition of any one of the preceding claims, the source of fluoride ions comprising or being selected from tetrabutylammonium fluoride, tetrabutylammonium tetrafluoroborate, and a combination thereof.

22. The oral care composition of any one of the preceding claims, the source of fluoride ions about 0.1 wt% to about 3 wt% with respect to the weight of the oral care composition.

23. The oral care composition of any one of the preceding claims, the source of calcium ions characterized by a water solubility of at least 1 g per liter of water at 20 °C.

24. The oral care composition of any one of the preceding claims, the source of calcium ions being an inorganic compound.

25. The oral care composition of any one of the preceding claims, the source of calcium ions comprising or being selected from calcium chloride, calcium nitrate, calcium sulfate, calcium dihydrogen phosphate, calcium hydrogen sulfate, calcium citrate, and a combination thereof.

26. The oral care composition of any one of the preceding claims, the source of calcium ions comprising or being an organic compound.

27. The oral care composition of any one of the preceding claims, the source of calcium ions comprising or being selected from calcium gluconate, calcium lactate, calcium lactate gluconate, calcium acetate, calcium citrate, calcium itaconate, and a combination thereof.

28. The oral care composition of any one of the preceding claims, the source of calcium ions being present in a total amount of about 0.01 wt% to about 2.0 wt% with respect to the weight of the oral care .

29. The oral care composition of any one of the preceding claims, the source of calcium ions and the water being present in weight ratio of about 1 : 10 to about 1 :2000.

30. The oral care composition of any one of the preceding claims, the source of fluoride ions and the source of calcium ions together provided as a chelating complex.

31. The oral care composition of any one of the preceding claims, the source of fluoride ions and the source of calcium ions together provided as a chelating complex, the chelating complex comprising citrate, etidronate, or a combination thereof.

32. The oral care composition of any one of claims 30-31, the chelating complex being a calcium citrate fluoride complex characterized by having at least 2 mole citrate for every 3 mole calcium and at least 1 mole of fluoride for every 1 mole calcium.

33. The oral care composition of any one of claims 30-32, the chelating complex present in an amount of about 0.01 wt% to about 2.0 wt% with respect to the weight of the oral care composition.

34. The oral care composition of any one of the preceding claims, further comprising a source of phosphate ions, the source of phosphate ions characterized by a water solubility of at least 1 g per liter of water at 20 °C.

35. The oral care composition of any one of the preceding claims, further comprising a source of phosphate ions, the source of phosphate ions comprising or being selected from sodium phosphate, sodium biphosphate, sodium triphosphate, potassium phosphate potassium biphosphate, potassium triphosphate, sodium potassium phosphate, ammonium hydrogen phosphate, and a combination thereof.

36. The oral care composition of any one of the preceding claims, further comprising a source of phosphate ions, the source of phosphate ions being present in a total amount of about 0.01 wt% to about 5 wt% with respect to the weight of the oral care composition.

37. The oral care composition of any one of claims 2-36, the silica as a thickening agent characterized by a mean particle size of no greater than 50 micron.

38. The oral care composition of any one of claims 2-37, the silica as a thickening agent comprising or being selected from diatomaceous earth, precipitated amorphous silica, amorphous silica gel, pyrogenic silica, fumed amorphous silica, fused amorphous silica, colloidal amorphous silica, and a combination thereof.

39. The oral care composition of any one clams 2-38, the silica as a thickening agent being present in an amount of about 1 wt% to about 10 wt% with respect to the weight of the oral care composition.

40. The oral care composition of any one of claims 2-39, the silica as a thickening and the abrasive agent being present in a weight ratio of about 1 :0.1 to about 1 :5.

41. The oral care composition of any one of claims 2-40, the abrasive agent comprising or being selected from silica, silica gel, hydrated silica precipitated silica, fused silica, alumina, calcined alumina, insoluble phosphates, calcium carbonate, ground glass, silicon carbide, ilmenite, sodium bicarbonate, bentonite, mica, zirconia, zirconia silicate, topaz, titanium dioxide, precipitated lime, chalk, pumice, zeolites, talcum, kaolin, diatomaceous earth, silicates, resinous abrasives, and a combination thereof.

42. The oral care composition of any one of claims 2-41, the abrasive agent being present in an amount of about 1 wt% to about 30 wt% with respect to the weight of the oral care composition.

43. The oral care composition of any one of claims 2-42, the abrasive agent and the water being present in a weight ratio of about 1 :2 to about 1:5.

44. The oral care composition of any one of the preceding claims, the water present in an amount of about 20 wt% to about 70 wt% with respect to the weight of the oral care composition.

45. The oral care composition of any one of the preceding claims, further comprising an organic thickener.

46. The oral care composition of any one of the preceding claims, further comprising a non- carboxylated polysaccharide thickener.

47. The oral care composition of any one of the preceding claims, further comprising hydroxyethyl cellulose as a thickener.

48. The oral care composition of any one of the preceding claims, further comprising an organic thickener present in an amount of about 0.1 wt% to about 2.5 wt% with respect to the weight of the oral care composition.

49. The oral care composition of any one of the preceding claims, further comprising an organic thickener, the organic thickener and the betaine compound present in a weight ratio of about 1 :4 to about 1:0.25.

50. The oral care composition of any one of the preceding claims, further comprising an organic thickener, the organic thickener and the water being present in a weight ratio of about 1 :200 to about 1:20.

51. The oral care composition of any one of the preceding claims, further comprising a sweetener.

52. The oral care composition of any one of the preceding claims, further comprising a desensitizing agent.

53. The oral care composition of any one of the preceding claims, further comprising a chelator compound.

54. The oral care composition of claim 53, the chelator compound selected from a citrate, an etidronate, or a combination thereof.

55. The oral care composition of any one of claims 53-54, the chelator compound present in an amount of about 0.01 wt% to about 0.5 wt% with respect to the weight of the oral care composition.

56. The oral care composition of any one of the preceding claims, excluding anionic surfactants.

57. The oral care composition of any one of the preceding claims, excluding sodium lauryl sulfate surfactant.

58. The oral care composition of any one of the preceding claims, characterized by a pH of about 5.5 to about 8.5.

59. The oral care composition of any one of the preceding claims, characterized by a viscosity of about 10,000 cP to about 800,000 cP at 20 °C.

60. The oral care composition of any one of the preceding claims, characterized as a colloid or a paste.

61. The oral care composition of any one of the preceding claims, being a toothpaste.

62. A method of preparing an oral care composition of any one of the preceding claims, the method comprising: providing and combining: a betaine compound of Formula I, a source of fluoride ions, a source of calcium ions, and water; and mixing to form the oral care composition.

63. A method of preparing an oral care composition of any one of claims 2-61, the method comprising: providing and combining: a betaine compound of Formula I,a source of fluoride ions, a source of calcium ions, a silica as a thickening agent, an abrasive agent, and water; and mixing to form the oral care composition.

64. A method of treating a tooth surface, the method comprising: contacting the oral care composition of any one of claims 1-61 to the tooth surface.

65. A method of cleaning and remineralizing a tooth surface, the method comprising: contacting the oral care composition of any one of claims 1-61 to the tooth surface.

66. A kit comprising: an oral care composition of any one of claims 1-61; and a set of instructions directing a user to contact the oral care composition to a tooth surface.

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