Remineralizing toothpaste

Abstract

Oral care compositions having a crosslinked polyacrylic acid, a source of fluoride ions, a source of calcium ions, thickening silica and an abrasive agent, and water are described. The oral care compositions are phase stable without requiring surfactants such as sodium lauryl sulfate.

Description

PA200043W002REMINERALIZING 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 surfactants.SUMMARY

[0004] In one embodiment, an oral care composition is described. The oral care composition includes a crosslinked polyacrylic acid, a source of fluoride ions, a source of calcium ions, a source of phosphate ions, a silica as a thickening agent, an abrasive agent, and water. The crosslinked polyacrylic acid and the water are present in a weight ratio of at least 1:6000.

[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 crosslinked polyacrylic acid, a source of fluoride ions, a source of calcium ions, a source of phosphate 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 a phase stable oral care composition (e.g., toothpaste) without requiring a surfactant. Fluoride ions, calcium ions, and phosphate ions are incorporated within the oral care composition and are made bioavailable by the presence of a crosslinked polyacrylic acid. Without wishing to be bound by theory, it is believed that the crosslinked polyacrylic acid may provide a network of proximate carboxylate groups in water (at suitable pH), even in the presence of thickeners and abrasives, that chelates or otherwise shelters calcium ions, thereby preventing the precipitation of calcium phosphate and / or calcium fluoride. The envisioned network is stable at a weight ratio of crosslinked polyacrylic acid: water at or above 1 :6000. Phase separation occurs below this weight ratio. In other words, the network is not stable when there is not enough polyacrylic acid or too much water.

[0010] Additionally, the network of proximate carboxylates in water with calcium (or other multivalent cations) can slow the release of fluoride tons. Sustained release of fluoride may allow for greater uptake of fluoride within the tooth structures.

[0011] The present disclosure provides a remineralizing toothpaste that does not require surfactants for stability and the lack of surfactants prolongs the shelf life in terms of remmeraiization potential. Moreover, the reminetalizing toothpaste of the present disclosure will not disrupt the protective mucin layer on soft tissues.Definitions

[0012] As used herein, “about” means ± 10 percent of a given value. For example, about 10 means 9 to 11.

[0013] As used herein, “acidic wt%” refers to the percentage of weight in any given compound that is due to acid / conjugate acid functional groups. Acid / conjugate acid functional groups are characterized by a pKa of no greater than 5. Example acid / conjugate acid functional groups include, but are not limited to, -CO2H / -CC . -P(O)(OH)2 / -P(O)(OH)O", and the like.

[0014] 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.

[0015] As used herein, “consisting essentially of’ means a limitation to the specified components and any components that do not affect the basic and novel characteristics. As used herein, “consisting only of’ means a limitation to only the specified components.

[0016] As used herein, “crosslinked” as used in “crosslinked polyacrylic acid” means there is a crosslinker compound covalently joining at least two polyacrylic acid polymers or covalently joining at least two areas within a polyacrylic acid.

[0017] As used herein, “crosslinker” refers to a compound with at least two functional groups that can form a bond between at least two polyacrylic acids or between at least two areas of a polyacrylic acid. For example, a crosslinker having at least two hydroxyl groups may crosslink polyacrylic acids by way of esterification.

[0018] As used herein, the phrase “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. For example, a weight ratio of “at least 1 :6000” includes 2:6000 = 1 :3000, 1000:6000 = 1 :6, or the like.

[0019] As used herein, “exclude” means that the referenced substance is not present, i.e., 0 wt.%.

[0020] 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.

[0021] As used herein, “polyacrylic acid” refers to compounds derived at least from monomers having an acrylate unit, i.e., C(R)2=C(R)-CC>2H, wherein each R is arbitrary, but often selected from - H and Ci-Ce alkyl. Although the term ‘polyacrylic acid’ suggests that the compounds are in acidic form, this is obviously dependent upon the pH. Thus, “polyacrylic acid” encompasses compounds that are fully protonated, fully deprotonated, and partially deprotonated. In many instances, “polyacrylic acid” may refer to compounds derived only from compounds having an acrylate unit.

[0022] 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.

[0023] 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.

[0024] 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.

[0025] 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

[0026] In various embodiments, an oral care composition is described. The oral care composition may include a crosslinked polyacrylic acid, 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 crosslinked polyacrylic acid and the water may be present in a weight ratio of at least 1:460.

[0027] In some embodiments, the oral care composition may further include a source of multivalent cation.

[0028] In some embodiments, the oral care composition may further include a source of phosphate ions.

[0029] In some embodiments, the oral care composition may further include an organic thickener.

[0030] In some embodiments, the oral care composition may further include a buffering agent.

[0031] In some embodiments, the oral care composition may further include a sweetener.

[0032] In some embodiments, the oral care composition may further include a desensitizing agent.

[0033] In some embodiments, the oral care composition may exclude surfactants, exclude anionic surfactants, cationic surfactant, nonionic surfactant, or specifically exclude sodium lauryl sulfate.

[0034] In some embodiments, the oral care composition may exclude other polymeric components having organic acid group(s) or conjugates thereof other than the crosslinked polyacrylic acid. In some embodiments, the oral care composition may exclude polymeric components having organic acid group(s) or conjugates thereof that are characterized by a molecular weight of no greater than 20,000 Da.

[0035] In some embodiments, the oral care composition may exclude enzymes. In other embodiments, any of the oral care compositions may further include one or more enzyme.

[0036] In some embodiments, any of the oral care compositions may further include a chelator compound.

[0037] In some embodiments, the oral care composition 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.

[0038] In some embodiments, the oral care composition may be characterized as a colloid.

[0039] In some embodiment, the oral care composition may be characterized as paste. Pastes of the present disclosure exclude liquid phase separation.

[0040] In some embodiments, the oral care composition 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.

[0041] In many embodiments, the oral care composition may be a toothpaste.

[0042] Further details are provided below.Crosslinked polyacrylic acid

[0043] Without wishing to be bound by theory, it is believed that the crosslinked polyacrylic acid serves to stabilize calcium within the system through chelation. It other words, the crosslinked polyacrylic acid prevents the precipitation of insoluble calcium salts, such as calcium fluoride and calcium phosphate. Furthermore, the crosslinked polyacrylic acid is essential to keep the oral care composition monophasic.

[0044] In some embodiments, the crosslinked poly acrylic acid may be characterized by a viscosity of about 25,000 cP to about 80,000 cP at 20°C and pH 7.5 as a 0.5 wt% aqueous solution (i.e., only water). For example, the crosslinked polyacrylic acid may be characterized by a viscosity (cP) of about 25,000; 30,000; 35,000; 40,000; 45,000; 50,000; 55,000; 60,000; 65,000; 70,000; 75,000; or 80,000, or a value within a range between any of the preceding values, e.g., between 30,000 cP to 60,000 cP, or the like.

[0045] In some embodiments, the crosslinked polyacrylic acid may be characterized by a water solubility of no greater than 1 g per L of water at 20 °C. For example, the crosslinked polyacrylic acid may be characterized by a water solubility of less than 1, less, 0.8, less than 0.5, less than 0.2, less than 0.1, less than 0.05, less than 0.01, less than 0.005, or less than 0.001.

[0046] In some embodiments, the crosslinked poly aery lie acid may be characterized by an acidic wt% of at least 30 wt%. The crosslinked polyacrylic acid may be characterized by an acidic wt% of about 30 wt% to about 55 wt% . For example, the crosslinked polyacrylic acid may be characterized by an acidic wt% of about 30, 32, 35, 38, 40, 42, 45, 48, 50, 52, or 55, or a value within a range between any of the preceding values, e.g., between about 40 wt% and about 52 wt%, or the like. Polyacidic medium with an acidic wt% of less than 30 wt% may not effectively chelate calcium. In some embodiments, the oral care composition may exclude polyacrylic acids that do not possess at least 30 wt% acids.

[0047] In some embodiments, the crosslinked polyacrylic acid may be characterized by an (alk)acrylic acid content of at least 80 wt% with respect to the weight of the polymer. That is, any crosslinked polyacrylic acid may be composed of at least 80 wt% (meth)acrylic acid (i.e., methacrylic acid, acrylic acid, or the combination thereof). For example, the crosslinked polyacrylic acid may be composed of one or more (alk)acrylic acid in an amount (wt%) of 80, 82, 85, 88, 90, 92, 95, 98, or 100, or a value within a range between any of the preceding values, e.g., between about 80 wt% and about 95 wt%, or the like. The remaining 20 wt% or less may be any other monomer, e.g., acrylates, such as methyl methacrylate, hydroxyethyl acrylate, or the like. Crosslinking agents are not included in this definition. Polyacidic medium with an an (alk)acrylic acid content of less than 80 wt% may not effectively chelate calcium. In some embodiments, the oral care composition may exclude polyacrylic acids that are not composed of at least 80 wt% (alk)acrylic acid content.

[0048] In some embodiments, the crosslinked polyacrylic acid may be characterized by a molecular weight of about 5xl05Da to about 10xl09Da. For example, the crosslinked polyacrylic acid may be characterized by a molecular weight (Da) of about 5xl05, 10xl05, 5xl06, 10xl06, 5xl07, 10xl07, 5xl08, 10xl08, 5xl09, 10xl09, or a value within a range between any of the preceding values, e.g., between about 10xl05Da to about 5xl09Da, or the like.

[0049] In some embodiments, the crosslinked polyacrylic acid may be a reaction product of a homopolymerized acrylic acid polymer and a crosslinker having at least two hydroxyl groups. In some embodiments, the crosslinker may be present within the crosslinked polyacrylic acid in an amount of about 0.5 wt% to about 5 wt%. In some embodiments, the crosslinker may be characterized by a molecular weight of about 90 g / mol to about 500 g / mol. For example, the crosslinker may be characterized by a molecular weight (g / mol) of about 90, 95, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, or 500, or a value within a range between any of the preceding values, e.g., between about 300 g / mol and about 375 g / mol, or the like. In some embodiments, the crosslinker may be selected from the crosslinker selected from allyl sucrose, pentaerythritol, glycerol, and a combination thereof.

[0050] In other embodiments, the crosslinked polyacrylic acid may be a reaction product of a copolymerized acrylic acid polymer and a crosslinker having at least two hydroxyl groups, such as the crosslinkers described above. In some embodiments, the copolymerized acrylic acid polymer may be a reaction product of acrylic acid and one or more acrylates monomer without acidic / carboxylate side group(s). In some embodiments, the co-monomer may be a C10-C30 alkyl acrylate, hydroxyethyl acrylate, or a combination thereof.

[0051] In many embodiments, the crosslinked polyacrylic acid may be present in an amount of about 0.015 wt% to about 2.0 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 0.015, 0.02, 0.025, 0.05, 0.08, 0.1, 0.15, 0.2, 0.25, 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, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, 1.95, or 2.0, or a value within a range between any of the preceding values, e.g., between about 0.2 wt% and about 1.5 wt%, or the like.

[0052] In many embodiments the crosslinked polyacrylic acid and the water may be present in a weight ratio of about 1:460 to about 1:5. For example, the crosslinked polyacrylic acid and the water may be present in a weight ratio of about 1:460, 1:450, 1:400, 1:390, 1:380, 1:370, 1:360, 1:350, 1:340, 1:330, 1:320, 1:310, 1:300, 1:290, 1:280, 1:270, 1:260, 1:250, 1:240, 1:230, 1:220, 1:210, 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, 1:20, 1:10, or 1:5, or a value within a range between any of the preceding values, e.g., between 1:250 and about 1 : 150, or the like. Too much water or too little crosslinked polyacrylic acid can result in an unstable composition that phase separates.

[0053] In some embodiments, the crosslinked polyacrylic acid and the source of calcium ions may be present in a weight ratio of about 200:1 to about 0.05:1. For example, the crosslinked polyacrylic acid and the source of calcium io ns may be present in a weight ratio of about 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, 30:1, 20:1, 15:1, 10:1, 9.5:1, 9:1, 8.5:1, 8:1, 7.8:1, 7.5:1, 7.2:1, 7:1, 6.5:1, 6:1, 5.8:1, 5.5:1, 5.2:1, 5:1, 4.8:1, 4.5:1, 4.2:1, 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, 0.8:1, 0.5:1, 0.2:1, 0.08:1, or 0.05:1, or a value within a range between any of the preceding values, e.g., between 6:1 to 3:1, or the like. Too many calcium ions or too little crosslinked polyacrylic acid can result in precipitation of insoluble calcium salts.

[0054] In some embodiments, the crosslinked polyacrylic acid and the thickening silica may be present in weight ratio of about 1:60 to about 1:0.5. For example, the crosslinked polyacrylic acid and the amorphous silica may be present in a weight ratio of about 1:60, 1:55, 1:50, 1:45, 1:40, 1:35, 1:30, 1:25, 1:22, 1:20, 1:18, 1:15, 1:12, 1:10, 1:8, 1:5, 1:2, 1:1, or 1:0.5, or a value within a range between any of the preceding values, e.g., between about 1:18 and about 1:15, or the like.

[0055] In some embodiments, the crosslinked polyacrylic acid and the abrasive agent may be present in a weight ratio of aboutl:0.5 to about 1:200. For example, the crosslinked polyacrylic acid and the abrasive agent may be present in a weight ratio of about 1:0.5, 1:1, 1:5, 1:10, 1:15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, 1:50, 1:55, 1:60, 1:65, 1:70, 1:75, 1:80, 1:85, 1:90, 1:95, 1:100, 1:110, 1:120, 1:130, 1:140, 1:150, 1:160, 1:170, 1:180, 1:190, or 1:200, or a value within a range between any of the preceding values, e.g., between about 1 :20 and about 1 :40, or the like.Source of fluoride ions

[0056] The oral care compositions of the present disclosure may include one or more sources of fluoride ions.

[0057] 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.

[0058] 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.

[0059] 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.

[0060] 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 maybe 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 a value within a range between any of the preceding values, e.g., between about 0.1 wt% and about 1.0 wt%, or the like.

[0061] 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 3.0, or a value within a range between any of the preceding values, e.g., between about 1 wt% and about 2.5 wt%, or the like.

[0062] 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, , ora value 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

[0063] The oral care compositions of the present disclosure may include one or more sources of calcium ions.

[0064] 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.

[0065] 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.

[0066] 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.

[0067] 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, gluconicacid / 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.

[0068] 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, the source 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.

[0069] 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

[0070] The oral care compositions of the present disclosure may further include one or more sources of phosphate ions.

[0071] In some embodiments, the source of phosphate ions 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.

[0072] In many embodiments, the source of phosphate ions may be an inorganic compound.

[0073] 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.

[0074] 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 avalue within a range between any of the preceding values, e.g., between about 0.05 wt% and about 1.0 wt%, or the like.

[0075] 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% with respect to the weight of the oral care composition. 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.

[0076] 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, oravalue 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

[0077] 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.

[0078] 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.

[0079] 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.

[0080] In some embodiments, the thickening silica and the abrasive agent may be present in a weight ratio of about 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

[0081] The abrasive agents of the present disclosure impart cleaning action upon contact with tooth structures.

[0082] 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.

[0083] 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.

[0084] In some embodiments, the abrasive agent may be present in an amount of about 1 wt% to about 40 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, 25, 30, 35, or 40, 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.

[0085] 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

[0086] 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%, between about 60 wt% and about 70 wt%, or the like.Multivalent Cation

[0087] The multivalent cations of the present disclosure do not encompass calcium ions even though calcium ions are technically a multivalent cation. Multivalent cations and calcium ions are intended to be treated as separate components. Both multivalent cations as described herein and calcium ions modulate the release of fluoride ions within the oral care compositions of the present disclosure.

[0088] In some embodiments, a source of multivalent cations may be characterized by a water solubility of at least 1 g per L of water at 20 °C. In some embodiments, the source of multivalent cations may be characterized by a water solubility of about 2.0 wt% to 45 wt% in water, or the like.

[0089] In some embodiments, a multivalent cation may be characterized by an oxidation state of 2+ or 3+.

[0090] In some embodiments, a multivalent cation may be an alkaline earth metal. In some embodiments, the multivalent cation may be a transition metal. In some embodiments, the multivalent cation may be a post-transition metal. In some embodiments, the multivalent cation may be a metalloid.

[0091] In some embodiments, a multivalent cation may be or may be selected from magnesium, strontium, barium, iron, zinc, copper, manganese, aluminum, iron, and a combination thereof.

[0092] In some embodiments, a source of multivalent cation may be an inorganic compound. The inorganic compound may include a counter anion selected from chloride, iodide, sulfate, nitrate, phosphate, or a combination thereof.

[0093] In other embodiments, a source of multivalent cation may be an organic compound. The organic compound may include a counter anion selected from gluconate, lactate, acetate, citrate, and itaconate.

[0094] In some embodiments, a source of multivalent cation may include or may be selected from aluminum chloride, aluminum sulfate, aluminum nitrate, potassium aluminum sulfate, and a combination of thereof.

[0095] In some embodiments, a source of multivalent cation (e.g., aluminum chloride) may be present in an amount of about 0.001 wt% to about 5 wt% with respect to the weight of the oral care composition. For example, the source of multivalent cation may be present in total amount (wt%) of about 0.001, 0.005, 0.01, 0.05, 0.1, 0.2, 0.5, 0.8, 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 0.1 wt% and about 1.0 wt%, or the like. Generally, greater amounts of multivalent cation (and / or calcium ions) further sustain the release of fluoride ions. Thus, the fluoride release profile for any given oral care composition may be tailored by adjusting the amount of multivalent cation (and / or calcium ions) present.

[0096] In some embodiments, a multivalent cation (e.g., aluminum 3+) may be present in amount of about 0.001 wt% to 1 wt% with respect to the weight of the oral care composition. For example, the multivalent cation may be present in total amount (wt%) of about 0.001, 0.005, 0.01, 0.05, 0.1, 0.15, 0.2, 0.25, 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, or 1, or a value within a range between any of the preceding values, e.g., between about 0.1 wt% and about 0.5 wt%, or the like.

[0097] In some embodiments, a source of multivalent cations (e.g., aluminum chloride) and the source of calcium ions may be present in weight ratio of about 0.1:1 to about 10:1. For example, a source of multivalent cations and the source of calcium ions may be present in a weight ratio of about 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, 1.5:1, 2:1, 2.5:1, 3: 1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 6.5:1, 7:1, 7.5:1, 8:1, 8.5:1, 9:1, 9.5:1, or 10:1, or a value within a range between any of thepreceding values, e.g., between 0.5: 1 to 1: 1, or the like. In some embodiments, multivalent cations (if present) and calcium ions, together, may be present in a total amount of at least 0.001 wt% with respect to the weight of the oral care composition. A combined amount of multivalent cations and calcium ions of at least 0.001 wt% may provide for slowed release of fluoride ions within the oral care composition.Organic Thickeners

[0098] The oral care compositions of the present disclosure may optionally further include one or more thickening agent that is an organic compound.

[0099] 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.

[0100] 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.

[0101] 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.

[0102] 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).

[0103] In some embodiments, an organic thickener may be present in an amount of about 0.1 wt% to about 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, 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 0.2 wt% and about 2 wt%, between about 0.01 wt% and about 2.5 wt%, or the like.

[0104] In some embodiments, an organic thickener and the crosslinked polyacrylic acid may be present in a weight ratio of about 1:4 to about 1:0.25. For example, the organic thickener and the crosslinked polyacrylic acid 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.

[0105] 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, or the like.Chelator Compound

[0106] 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.

[0107] 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 oral care 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.

[0108] 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

[0109] 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 otherembodiments, the oral care composition may exclude one or more of the aforementioned classes or exclude one or more of the following specific components.

[0110] 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.

[0111] 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.

[0112] 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.

[0113] 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 present in 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%.

[0114] 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.

[0115] Example anti-calculus include, but is not limited to, pyrophosphates, polyolefin sulfonates, polyolefin phosphates, diphosphonates, and phosphonoalkane carboxylic acids.

[0116] 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.

[0117] Example saliva-stimulating agents include, but not limited to, citric acid, lactic acid, succinic acid, ascorbic acid, adipic acid, fumaric acid, and tartaric acid.

[0118] Example breath-freshening agents include, but not limited to, zinc salts such as zinc gluconate, zinc citrate, zinc chlorite, and alpha-ionone.

[0119] 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.

[0120] 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.

[0121] Example histamine H2antagonists include, but not limited to, cimetidine, ranitidine, tiotidine, lupitidine, famotidine, roxatidine, lamtidine, zaltidine, nizatidine, mifentidine, lavoltidine, bisfentidine, sufotidine, ebrotidine, and impromidine.METHODS FOR PREPARING ORAL CARE COMPOSITIONS

[0122] 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 crosslinked polyacrylic acid, 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

[0123] 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.

[0124] 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.

[0125] In many embodiments, the methods may further include brushing or otherwise scrubbing the tooth surface having the oral care composition thereon.KITS

[0126] 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

[0127] 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

[0128] 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

[0129] 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

[0130] 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 SOLUTIONS and COMPARATIVE PREPARATORY SOLUTIONSPreparation of Buffered CARBOPOL Polyacid Solutions

[0131] Alkaline chemicals, such as disodium hydrogen phosphate, triethanolamine, were first dissolved in deionized (DI) water in a glass jar to form clear solutions. Then CARBOPOL 974P NF was added into the glass jar, which was roller mixed to form solutions which were slightly viscous and slightly hazy. The pH was measured with a standard pH meter.

[0132] Buffered CARBOPOL polyacid solutions were added to a plastic bottle followed by the addition of sodium fluoride, xylitol, flavor / sweetener. The resulting mixture was magnetically stirred for 30 min to dissolve all these chemicals. Multivalent cation salts were first dissolved in DI water in a separate glass jar and resulting salt solutions were added slowly into the CARBOPOL solution. The mixture was mixed with magnetic stirring for 1 h. Hydroxyl ethyl cellulose (HEC) was the added into the solutions and mixed for another 30 min with magnetic stirring. The preparatory compositions were further mixed on a roller mixer for 1 -2 days to form viscous aqueous liquid. The total amount (in grams) of each component within the preparatory solutions and comparative preparatory solutions is shown in Table A.

[0133] The solutions of Table A were then tested for fluoride release according to the method described above. The results are tabulated in Table B.Table A. Preparatory Solutions PS. 1 - 8 and Comparative Preparatory Solutions CPS. 1-2.Table B. Rate of Fluoride Release for Preparatory Solutions

[0134] The data in Table B demonstrates that aluminum cations and calcium cations can slow the release of fluoride in compositions having a polyacrylic acid polymer. The data also suggests that iron, strontium, and zinc cations may also slow the release of fluoride. Moreover, the preparatory solutions demonstrate that calcium ions, fluoride ions, and phosphate ions can be combined without precipitation of calcium fluoride or calcium phosphate.PREPARATORY CALCIUM CHELATE FLUORIDE COMPLEX

[0135] 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.

[0136] 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.EXAMPLES 1-11 and COMPARATIVE EXAMPLES 1-2

[0137] Preparatory solutions of polyacrylic acid polymer, aluminum chloride, calcium chloride, sodium fluoride, and sodium phosphate with a hydroxyethyl cellulose thickener were prepared according to the details above. The resulting solutions were then mixed with a silica thickener, a silica abrasive at 3000 rpm for 2 min (x 3). The example compositions and comparative compositions are tabulated in Tables 1A-1B below. A calcium citrate fluoride complex, as described above, was further added Examples 10 and 11 to illustrate the stability of said complex within a toothpaste formulation. Stability data is also provided in Tables 1A-1B for each composition.

[0138] Fluoride-release data is tabulated in Table 2 and calcium-release data is tabulated in Table 3. Ion release data for ClinPro™ 5000 also appears in Tables 2-3 as a comparative.Table 1A. Toothpaste Formulations EX. 1 - EX. 7Table IB. Toothpaste formulations EX. 8 - EX. 11 and CE. 1 - CE. 2

[0139] The data indicates that at least 0.01 wt% of the crosslinked polyacrylic acid polymer is required to prevent phase separation of compositions having more than 60 wt% water, or otherwise a crosslinked polyacrylic acid polymer: water weight ratio of at least 1:6000.Table 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™ degradesand some degradation products have been shown to prematurely convert TCP to hydroxyapatite, which is less useful for remineralization.EQUIVALENTS Those 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 crosslinked polyacrylic acid; a source of fluoride ions; a source of calcium ions; a silica as a thickening agent; an abrasive agent; and water, wherein the crosslinked polyacrylic acid and the water are present in a weight ratio of at least 1:460.

2. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic acid characterized by a viscosity of about 25,000 cP to about 80,000 cP at 20°C and pH 7.5 as a 0.5 wt% aqueous solution.

3. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic acid characterized by an acidic wt% of at least 30 wt%.

4. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic acid characterized as being composed of at least 80 wt% (alk)acrylic acid monomer units.

5. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic acid characterized by a molecular weight of about 5xl05Da to about 10xl09Da.

6. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic acid being a reaction product of a homopolymerized acrylic acid polymer and a crosslinker having at least two hydroxyl groups.

7. The oral care composition of any one of claims 1-5, the crosslinked polyacrylic acid being a reaction product of a copolymerized acrylic acid polymer and a crosslinker having at least two hydroxyl groups.

8. The oral care composition of claim 7, the copolymerized acrylic acid polymer being a reaction product of acrylic acid and a C10-C30 alkyl acrylate.

9. The oral care composition of any one of claims 6-8, the crosslinker selected from allyl sucrose, pentaerythritol, glycerol, and a combination thereof.

10. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic being present in an amount of 0.015 wt% to about 2.0 wt% with respect to the weight of the oral care composition.

11. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic acid and the water being present in a weight ratio of about 1 :460 to about 1:5.

12. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic acid and the source of calcium ions being present in a weight ratio of about 200: 1 to about 0.05: 1.

13. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic acid and the silica as a thickening agent being present in a weight ratio of about 1 :60 to about 1:0.5.

14. The oral care composition of any one of the preceding claims, the crosslinked polyacrylic acid and the abrasive agent being present in a weight ratio of about 1:0.5 to about 1:200.

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 BF4.

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 present in a total amount of about 0.1 wt% to about 2.5 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 fluoride ions providing 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.

24. 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.

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

26. 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, and a combination thereof.

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

28. 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.

29. 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.

30. The oral care composition of any one of the preceding claims, the source of calcium ions and a source of phosphate ions being present in a weight ratio of about 1:0.05 to about 1: 100.

31. 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.

32. 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.

33. 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.

34. The oral care composition of any one of claims 32-33, 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.

35. The oral care composition of any one of claims 32-34, 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.

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

37. The oral care composition of any one of the preceding claims, 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.

38. 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.

39. The oral care composition of any one of the preceding claims, the silica as a thickening agent characterized by a median particle size of no greater than 50 micron.

40. The oral care composition of any one of the preceding claims, 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.

41. The oral care composition of any one of the preceding claims, 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.

42. The oral care composition of any one of the preceding claims, the silica as a thickening and the abrasive agent being present in a weight ratio of about 1 : 0.5 to about 1:5.

43. The oral care composition of any one of the preceding claims, 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.

44. The oral care composition of any one of the preceding claims, the abrasive agent being present in an amount of about 5 wt% to about 20 wt% with respect to the weight of the oral care composition.

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

46. 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.

47. The oral care composition of any one of the preceding claims, further comprising a source of multivalent cation characterized by a water solubility of at least 1 g per L of water at 20 °C.

48. The oral care composition of any one of the preceding claims, further comprising a source of multivalent cation, the multivalent cation being an alkaline earth metal.

49. The oral care composition of any one of the preceding claims, further comprising a source of multivalent cation, the multivalent cation being a transition metal.

50. The oral care composition of any one of the preceding claims, further comprising a source of multivalent cation, the multivalent cation being a post-transition metal or a metalloid.

51. The oral care composition of any one of the preceding claims, further comprising a source of multivalent cation, the multivalent cation selected from magnesium, strontium, barium, iron, zinc, copper, manganese, aluminum, iron, and a combination thereof.

52. The oral care composition of any one of the preceding claims, further comprising a source of multivalent cation comprising or being selected from aluminum chloride, aluminum sulfate, aluminum nitrate, potassium aluminum sulfate, and a combination of thereof.

53. The oral composition of any one of the preceding claims, further comprising a source of multivalent cation, the source of multivalent cation comprising or being aluminum chloride.

54. The oral care composition of any one of the preceding claims, further comprising a source of multivalent cation, the source of multivalent cation being present in an amount of about 0.01 wt% to about 5 wt% with respect to the weight of the oral care composition.

55. The oral care composition of any one of the preceding claims, further comprising a source of multivalent cation, the source of multivalent cation and the source of calcium ions being present in weight ratio of about 0.1 : 1 to about 10:1.

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

57. The oral care composition of any one of the preceding claims, further include a non-acidic polysaccharide thickener.

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

59. 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 5 wt% with respect to the weight of the oral care composition.

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

61. 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.

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

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

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

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

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

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

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

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

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

71. A method of preparing an oral care composition of any one of claims 1-70, the method comprising:providing and combining: a crosslinked polyacrylic acid, 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.

72. A method of treating a tooth surface, the method comprising: contacting the oral care composition of any one of claims 1-70 to the tooth surface.

73. A method of cleaning and remineralizing a tooth surface, the method comprising: contacting the oral care composition of any one of claims 1-70 to the tooth surface.

74. A kit comprising: an oral care composition of any one of claims 1-70; and a set of instructions directing a user to contact the oral care composition to a tooth surface.

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