Oral Care Compositions and Methods of Use

Abstract

This disclosure relates to translucent oral care compositions comprising one or more source(s) of zinc source and/or a stannous source. The translucent oral care composition can comprise one or more zinc and/or stannous ion source(s) in amounts effective to provide at least 28% soluble zinc and/or stannous as a fraction of the total zinc and/or stannous ion concentration in the composition; an abrasive (e.g., silica), wherein the abrasive has a refractive index of approximately 1.45 as measured in a 4% silica, 90% sorbitol/water solution; and an orally acceptable vehicle. Methods of using and of making these compositions is also disclosed herein.

Claims

1. A translucent oral care composition comprising: a. One or more zinc ion source(s) and/or stannous ion source(s); wherein the zinc and/or stannous ion source(s) are in amounts effective to provide at least 28% soluble zinc and/or stannous as a fraction of the total zinc and/or stannous ion concentration in the composition; b. An abrasive (e.g., silica), wherein the abrasive has a refractive index of approximately 1.45 as measured in a 4% silica, 90% sorbitol/water solution; and c. An orally acceptable vehicle.

2. The oral care composition of claim 1, wherein the composition comprises one or more zinc ion sources, and wherein the one or more sources of zinc ion source(s) comprises a zinc salt selected from the group consisting of: zinc citrate, zinc oxide, zinc phosphate, zinc lactate, zinc sulfate, zinc silicate and combinations thereof.

3. The oral care composition of claim 1, wherein the composition comprises a source of zinc ion, and wherein the zinc ion source comprises zinc oxide.

4. The oral care composition of claim 1, wherein the composition comprises a source of zinc ion, and wherein the zinc ion source comprises zinc citrate.

5. The oral care composition of claim 1, wherein the composition comprises one or more sources of zinc ion, and wherein the one or more sources of zinc ion comprises zinc oxide and zinc citrate.

6. The oral care composition of claim 1, wherein the composition comprises a source of zinc ion, and wherein the zinc ion source comprises zinc phosphate.

7. The oral care composition of claim 1, wherein the composition comprises a stannous ion source.

8. The oral care composition of claim 7, wherein the stannous ion source is selected from the group consisting of: stannous fluoride, other stannous halides (e.g., stannous chloride dihydrate), stannous pyrophosphate, organic stannous carboxylate salts, stannous ethylene glyoxide, and combinations thereof.

9. The oral care composition of claim 7, wherein the stannous ion source is stannous fluoride.

10. The oral care composition of claim 1, wherein the composition comprises a silica abrasive having a N.sub.2 BET surface area of less than 50 m.sup.2/g and an Einlehner hardness of from 4 to 11; for example wherein the silica abrasive (e.g., Sylodent VP5) has the following physical properties: TABLE-US-00011 N.sub.2 BET surface area (m.sup.2/g) <50 Oil absorption (cc/100 g) 80-100 Mean particle size (μm) 9-13 d10 (μm) 2.74 Brass Einlehner hardness 6-9 

11. (canceled)

12. The oral care composition of claim 1, wherein the silica abrasive has a refractive index of approximately 1.45 as measured in a 4% silica, 90% sorbitol/water solution.

13. The oral care composition of claim 1 comprising an amino acid source, wherein the amino acid source comprises a basic amino acid; for example wherein the amino acid source comprises an amino acid selected from the group consisting of arginine, lysine, glycine and combinations thereof for example wherein the amino acid source comprises arginine.

14. (canceled)

15. (canceled)

16. The oral care composition of claim 1, wherein the composition comprises: a. Zinc oxide and/or zinc citrate; b. sodium fluoride; c. an abrasive (e.g., silica), wherein the abrasive has a refractive index of approximately 1.45 as measured in a 4% silica, 90% sorbitol/water solution; d. wherein the amounts of zinc oxide and zinc citrate are effective to provide at least 28% soluble zinc ion concentration as a fraction of the total concentration in the composition; e. an orally acceptable carrier; and f. arginine.

17. The oral care composition of claim 1, wherein the composition comprises: a. zinc phosphate b. stannous fluoride; c. An abrasive (e.g., silica), wherein the abrasive has a refractive index of approximately 1.45 as measured in a 4% silica, 90% sorbitol/water solution; d. an orally acceptable carrier; wherein the amount of zinc phosphate and stannous fluoride is effective to provide at least 28% soluble metal ion concentration as a fraction of the total concentration in the composition; and wherein the amount of water is more than 10% by wt. of the composition; an orally acceptable carrier.

18. The oral care composition of claim 1, wherein the composition comprises sodium citrate; for example wherein the composition comprises trisodium citrate; for example wherein the composition comprises trisodium citrate in an amount from 2%-7% by wt. of the total composition.

19. (canceled)

20. (canceled)

21. The oral care composition of claim 1, wherein the amount of soluble metal ion(s) in the composition is from 28%-95%.

22. (canceled)

23. A method to improve oral health comprising applying an effective amount of the oral composition of claim 1 to the oral cavity of a subject in need thereof.

24. A method for producing a translucent oral care composition according to claim 1, wherein the method comprises combining one or more zinc ion source(s) and/or stannous ion source(s) in an orally acceptable carrier; wherein the zinc and/or stannous ion source(s) are in amounts effective to provide at least 28% soluble zinc and/or stannous as a fraction of the total zinc and/or stannous ion concentration in the composition); and combining with an abrasive, wherein the abrasive has a refractive index of approximately 1-2 as measured in a 4% silica, 90% sorbitol/water solution; and sodium citrate in an amount from 2%-7% by wt. of the total composition.

25. A method for increasing: a) antibacterial efficacy; and/or b) optical transmission of an aqueous oral care composition, said composition comprising one or more zinc ion source(s) and/or stannous ion source(s), and an abrasive (e.g., silica), wherein the abrasive has a refractive index of approximately 1.45 as measured in a 4% silica, 90% sorbitol/water solution; the method comprising formulating the composition to include a zinc ion and/or stannous ion solubilizing agent; e.g. wherein the solubilizing agent comprises citrate ion; e.g. wherein the solubilizing agent comprises trisodium citrate.

26. The method according to claim 25, wherein the aqueous oral care composition is a composition according to claim 1.

Description

DETAILED DESCRIPTION

[0176] As used herein, the term “dentifrice” means paste, gel, or liquid formulations unless otherwise specified. The dentifrice composition can be in any desired form such as deep striped, surface striped, multi-layered, having the gel surrounding the paste, or any combination thereof. Alternatively, the oral composition may be dual phase dispensed from a separated compartment dispenser.

[0177] As used herein, an “oral care composition” refers to a composition for which the intended use includes oral care, oral hygiene, and/or oral appearance, or for which the intended method of use comprises administration to the oral cavity, and refers to compositions that are palatable and safe for topical administration to the oral cavity, and for providing a benefit to the teeth and/or oral cavity. The term “oral care composition” thus specifically excludes compositions which are highly toxic, unpalatable, or otherwise unsuitable for administration to the oral cavity. In some embodiments, an oral care composition is not intentionally swallowed, but is rather retained in the oral cavity for a time sufficient to affect the intended utility. The oral care compositions as disclosed herein may be used in nonhuman mammals such as companion animals (e.g., dogs and cats), as well as by humans. In some embodiments, the oral care compositions as disclosed herein are used by humans. Oral care compositions include, for example, dentifrice and mouthwash. In some embodiments, the disclosure provides mouthwash formulations.

[0178] As used herein, “orally acceptable” refers to a material that is safe and palatable at the relevant concentrations for use in an oral care formulation, such as a mouthwash or dentifrice.

[0179] As used herein, “orally acceptable carrier” refers to any vehicle useful in formulating the oral care compositions disclosed herein. The orally acceptable carrier is not harmful to a mammal in amounts disclosed herein when retained in the mouth, without swallowing, for a period sufficient to permit effective contact with a dental surface as required herein. In general, the orally acceptable carrier is not harmful even if unintentionally swallowed. Suitable orally acceptable carriers include, for example, one or more of the following: water, a thickener, a buffer, a humectant, a surfactant, an abrasive, a sweetener, a flavorant, a pigment, a dye, an anti-caries agent, an anti-bacterial, a whitening agent, a desensitizing agent, a vitamin, a preservative, an enzyme, and mixtures thereof.

[0180] As used herein throughout, the terms “soluble” and “solubility” refer to aqueous solubility (i.e., the solubility of the described species in water). As used herein, the term “soluble” refers to a compound having a solubility product constant (K.sub.SP) in water of greater than or equal to 1×10.sup.−10 (at 20° C.). As used herein, the term “insoluble” refers to a compound having a solubility product constant (K.sub.SP) in water of less than 1×10.sup.−10 (at 20° C.).

[0181] Insoluble zinc compounds include, but are not limited to, zinc oxide, zinc phosphate, zinc pyrophosphate, zinc silicate, zinc oleate, zinc hydroxide, zinc carbonate, zinc peroxide and zinc sulfide. By way of comparison, soluble zinc compounds include zinc citrate, zinc chloride, zinc lactate, zinc nitrate, zinc acetate, zinc glycinate and zinc sulfate.

[0182] Insoluble stannous compounds include, but are not limited to, stannous phosphate (i.e., stannous orthophosphate), stannous pyrophosphate, stannous oxide, stannous sulfate, stannous peroxide, and stannous hydroxide. By way of comparison, soluble stannous compounds include stannous fluoride, stannous chloride, stannous nitrate and stannous sulfate.

[0183] As used herein throughout, the term “zinc ion and/or stannous ion solubilizing agent” refers to a compound that functions in the formulation to increase the solubility of one or both of zinc ions and stannous ions. Examples of such solubilizing agents include citrate salts, for example trisodium citrate; e.g., in an amount from 2%-7% by wt. of the total composition.

Fluoride Ion Source

[0184] The oral care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may further include one or more fluoride ion sources, e.g., soluble fluoride salts. A wide variety of fluoride ion-yielding materials can be employed as sources of soluble fluoride in the present compositions. Examples of suitable fluoride ion-yielding materials are found in U.S. Pat. No. 3,535,421, to Briner et al.; U.S. Pat. No. 4,885,155, to Parran, Jr. et al. and U.S. Pat. No. 3,678,154, to Widder et al., each of which are incorporated herein by reference. Representative fluoride ion sources used with the present invention (e.g., Composition 1.0 et seq.) include, but are not limited to, stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, and combinations thereof. In certain embodiments the fluoride ion source includes stannous fluoride, sodium fluoride, sodium monofluorophosphate as well as mixtures thereof. Where the formulation comprises calcium salts, the fluoride salts are preferably salts wherein the fluoride is covalently bound to another atom, e.g., as in sodium monofluorophosphate, rather than merely ionically bound, e.g., as in sodium fluoride.

Surfactants

[0185] The oral care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may contain anionic surfactants, for example, water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the monosulfated monoglyceride of hydrogenated coconut oil fatty acids such as sodium N-methyl N-cocoyl taurate, sodium cocomo-glyceride sulfate; higher alkyl sulfates, such as sodium lauryl sulfate; higher alkyl-ether sulfates, e.g., of formula CH.sub.3(CH.sub.2).sub.mCH.sub.2(OCH.sub.2CH.sub.2).sub.nOSO.sub.3X, wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2, 3 or 4, and X is Na or, for example sodium laureth-2 sulfate (CH.sub.3(CH.sub.2).sub.10CH.sub.2(OCH.sub.2CH.sub.2).sub.2OSO.sub.3Na); higher alkyl aryl sulfonates such as sodium dodecyl benzene sulfonate (sodium lauryl benzene sulfonate); higher alkyl sulfoacetates, such as sodium lauryl sulfoacetate (dodecyl sodium sulfoacetate), higher fatty acid esters of 1,2 dihydroxy propane sulfonate, sulfocolaurate (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl sarcosinate. By “higher alkyl” is meant, e.g., C.sub.6-3o alkyl. In particular embodiments, the anionic surfactant (where present) is selected from sodium lauryl sulfate and sodium ether lauryl sulfate. When present, the anionic surfactant is present in an amount which is effective, e.g., >0.001% by weight of the formulation, but not at a concentration which would be irritating to the oral tissue, e.g., 1%, and optimal concentrations depend on the particular formulation and the particular surfactant. In one embodiment, the anionic surfactant is present at from 0.03% to 5% by weight, e.g., about 1.75% by wt.

[0186] In another embodiment, cationic surfactants useful in the present invention can be broadly defined as derivatives of aliphatic quaternary ammonium compounds having one long alkyl chain containing 8 to 18 carbon atoms such as lauryl trimethylammonium chloride, cetyl pyridinium chloride, cetyl trimethylammonium bromide, di-isobutylphenoxyethyldimethylbenzylammonium chloride, coconut alkyltrimethylammonium nitrite, cetyl pyridinium fluoride, and mixtures thereof. Illustrative cationic surfactants are the quaternary ammonium fluorides described in U.S. Pat. No. 3,535,421, to Briner et al., herein incorporated by reference. Certain cationic surfactants can also act as germicides in the compositions.

[0187] Illustrative nonionic surfactants of the disclosure, e.g., any of Composition 1.0, et seq., that can be used in the compositions of the disclosure can be broadly defined as compounds produced by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound which may be aliphatic or alkylaromatic in nature. Examples of suitable nonionic surfactants include, but are not limited to, the Pluronics, polyethylene oxide condensates of alkyl phenols, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylene diamine, ethylene oxide condensates of aliphatic alcohols, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides and mixtures of such materials. In a particular embodiment, the composition of the invention comprises a nonionic surfactant selected from polaxamers (e.g., polaxamer 407), polysorbates (e.g., polysorbate 20), polyoxyl hydrogenated castor oils (e.g., polyoxyl 40 hydrogenated castor oil), and mixtures thereof.

[0188] Illustrative amphoteric surfactants of Composition 1.0, et seq., that can be used in the compositions of the invention include betaines (such as cocamidopropylbetaine), derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be a straight or branched chain and wherein one of the aliphatic substituents contains about 8-18 carbon atoms and one contains an anionic water-solubilizing group (such as carboxylate, sulfonate, sulfate, phosphate or phosphonate), and mixtures of such materials.

[0189] The surfactant or mixtures of compatible surfactants can be present in the compositions of the present invention in 0.1% to 5%, in another embodiment 0.3% to 3% and in another embodiment 0.5% to 2% by weight of the total composition.

Flavoring Agents

[0190] The oral care compositions of the disclosure, e.g., any of Composition 1.0 et seq., may also include a flavoring agent. Flavoring agents which are used in the practice of the present invention include, but are not limited to, essential oils and various flavoring aldehydes, esters, alcohols, and similar materials, as well as sweeteners such as sodium saccharin. Examples of the essential oils include oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Also useful are such chemicals as menthol, carvone, and anethole. Certain embodiments employ the oils of peppermint and spearmint.

[0191] The flavoring agent is incorporated in the oral composition at a concentration of 0.01 to 1% by weight.

pH Adjusting Agents

[0192] In some embodiments, the compositions of the present disclosure, e.g., any of Composition 1.0 et seq, contain a buffering agent. Examples of buffering agents include anhydrous carbonates such as sodium carbonate, sesquicarbonates, bicarbonates such as sodium bicarbonate, silicates, bisulfates, phosphates (e.g., monopotassium phosphate, monosodium phosphate, disodium phosphate, dipotassium phosphate, tribasic sodium phosphate, sodium tripolyphosphate, pentapotassium tripolyphosphate, phosphoric acid), citrates (e.g. citric acid, trisodium citrate dehydrate), pyrophosphates (sodium and potassium salts, e.g., tetrapotassium pyrophosphate) and combinations thereof. The amount of buffering agent is sufficient to provide a pH of about 5 to about 9, preferable about 6 to about 8, and more preferable about 7, when the composition is dissolved in water, a mouthrinse base, or a toothpaste base. Typical amounts of buffering agent are about 5% to about 35%, in one embodiment about 10% to about 30%, in another embodiment about 15% to about 25%, by weight of the total composition.

Chelating and Anti-Calculus Agents

[0193] The oral care compositions of the disclosure, e.g., any of Composition 1.0 et seq., also may include one or more chelating agents able to complex calcium found in the cell walls of the bacteria. Binding of this calcium weakens the bacterial cell wall and augments bacterial lysis.

[0194] Another group of agents suitable for use as chelating or anti-calculus agents in the present invention are the soluble pyrophosphates. The pyrophosphate salts used in the present compositions can be any of the alkali metal pyrophosphate salts. In certain embodiments, salts include tetra alkali metal pyrophosphate, dialkali metal diacid pyrophosphate, trialkali metal monoacid pyrophosphate and mixtures thereof, wherein the alkali metals are sodium or potassium. The salts are useful in both their hydrated and unhydrated forms. An effective amount of pyrophosphate salt useful in the present composition is generally enough to provide at least 0.1 wt. % pyrophosphate ions, e.g., 0.1 to 3 wt. %, e.g., 0.1 to 2 wt. %, e.g., 0.1 to 1 wt. %, e.g., 0.2 to 0.5 wt. %. The pyrophosphates also contribute to preservation of the compositions by lowering water activity.

[0195] Suitable anticalculus agents for the compositions of the disclosure (e.g., any of Composition 1.0 et seq) include without limitation phosphates and polyphosphates (for example pyrophosphates), polyaminopropanesulfonic acid (AMPS), hexametaphosphate salts, zinc citrate trihydrate, polypeptides, polyolefin sulfonates, polyolefin phosphates, diphosphonates. In particular embodiments, the invention includes alkali phosphate salts, i.e., salts of alkali metal hydroxides or alkaline earth hydroxides, for example, sodium, potassium or calcium salts. “Phosphate” as used herein encompasses orally acceptable mono- and polyphosphates, for example, P.sub.1-6 phosphates, for example monomeric phosphates such as monobasic, dibasic or tribasic phosphate; dimeric phosphates such as pyrophosphates; and multimeric phosphates, e.g., sodium hexametaphosphate. In particular examples, the selected phosphate is selected from alkali dibasic phosphate and alkali pyrophosphate salts, e.g., selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, and mixtures of any of two or more of these. In a particular embodiment, for example the compositions comprise a mixture of tetrasodium pyrophosphate (Na.sub.4P.sub.2O.sub.7), calcium pyrophosphate (Ca.sub.2P.sub.2O.sub.7), and sodium phosphate dibasic (Na.sub.2HPO.sub.4), e.g., in amounts of ca. 3-4% of the sodium phosphate dibasic and ca. 0.2-1% of each of the pyrophosphates. In another embodiment, the compositions comprise a mixture of tetrasodium pyrophosphate (TSPP) and sodium tripolyphosphate (STPP)(Na.sub.5P.sub.3O.sub.10), e.g., in proportions of TSPP at about 1-2% and STPP at about 7% to about 10%. Such phosphates are provided in an amount effective to reduce erosion of the enamel, to aid in cleaning the teeth, and/or to reduce tartar buildup on the teeth, for example in an amount of 2-20%, e.g., ca. 5-15%, by weight of the composition.

Polymers

[0196] The oral care compositions of the disclosure, e.g., any of Composition 1.0 et seq., also optionally include one or more polymers, such as polyethylene glycols, polyvinyl methyl ether maleic acid copolymers, polysaccharides (e.g., cellulose derivatives, for example carboxymethyl cellulose, or polysaccharide gums, for example xanthan gum or carrageenan gum). Acidic polymers, for example polyacrylate gels, may be provided in the form of their free acids or partially or fully neutralized water soluble alkali metal (e.g., potassium and sodium) or ammonium salts. Certain embodiments include 1:4 to 4:1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer, for example, methyl vinyl ether (methoxyethylene) having a molecular weight (M.W.) of about 30,000 to about 1,000,000. These copolymers are available for example as Gantrez AN 139 (M.W. 500,000), AN 1 19 (M.W. 250,000) and S-97 Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals Corporation.

[0197] Other operative polymers include those such as the 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being available for example as Monsanto EMA No. 1 103, M.W. 10,000 and EMA Grade 61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

[0198] The N-vinyl-2-pyrrolidione is also commonly known as polyvinylpyrrolidone or “PVP”. PVP refers to a polymer containing vinylpyrrolidone (also referred to as N-vinylpyrrnlidone and N-vinyl-2-pyrrolidinone) as a monomeric unit. The monomeric unit consists of a polar imide group, four non-polar methylene groups and a non-polar methane group. The polymers include soluble and insoluble homopolymeric PVPs. Copolymers containing PVP include vinylpyrrolidone/vinyl acetate (also known as Copolyvidone, Copolyvidonum or VP-VAc) and vinyl pyrrolidone/dimethylamino-ethylmethacrylate. Soluble PVP polymers among those useful herein are known in the art, including Povidone, Polyvidone, Polyvidonum, poly(N-vinyl-2-pyrrolidinone), poly (N-vinylbutyrolactam), poly(1-vinyl-2-pyrrolidone) and poly [1-(2-oxo-1 pyrrolidinyl)ethylene]. These PVP polymers are not substantially cross-linked. In some embodiments the polymer comprises an insoluble cross-linked homopolymer. Such polymers include crosslinked PVP (often referred to as cPVP, polyvinylpolypyrrolidone, or cross-povidone).

[0199] Suitable generally, are polymerized olefinically or ethylenically unsaturated carboxylic acids containing an activated carbon-to-carbon olefinic double bond and at least one carboxyl group, that is, an acid containing an olefinic double bond which readily functions in polymerization because of its presence in the monomer molecule either in the alpha-beta position with respect to a carboxyl group or as part of a terminal methylene grouping. Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic acids and anhydrides. Other different olefinic monomers copolymerizable with such carboxylic monomers include vinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymers contain sufficient carboxylic salt groups for water-solubility.

[0200] A further class of polymeric agents includes a composition containing homopolymers of substituted acrylamides and/or homopolymers of unsaturated sulfonic acids and salts thereof, in particular where polymers are based on unsaturated sulfonic acids selected from acrylamidoalykane sulfonic acids such as 2-acrylamide 2 methylpropane sulfonic acid having a molecular weight of about 1,000 to about 2,000,000, described in U.S. Pat. No. 4,842,847, Jun. 27, 1989 to Zahid, incorporated herein by reference.

[0201] In preparing oral care compositions, it is sometimes necessary to add some thickening material to provide a desirable consistency or to stabilize or enhance the performance of the formulation. In certain embodiments, the thickening agents are carboxyvinyl polymers, carrageenan, xanthan, hydroxyethyl cellulose and water soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums such as karaya, gum arabic, and gum tragacanth can also be incorporated. Colloidal magnesium aluminum silicate or finely divided silica can be used as component of the thickening composition to further improve the composition's texture. In certain embodiments, thickening agents in an amount of about 0.5% to about 5.0% by weight of the total composition are used.

[0202] In some embodiments, microcrystalline cellulose (MCC) can be used (e.g., carboxymethyl cellulose with sodium carboxymethyl cellulose). An example of a source of MCC is Avicel® (FMC Corporation), which contains MCC in combination with sodium carboxymethyl cellulose (NaCMC). Both Avicel®. RC-591 (MCC containing 8.3 to 13.8 weight % NaCMC) and Avicel®. CL-611 (MCC containing 11.3 to 18.8 weight % NaCMC) may be used in certain aspects. In certain embodiments, the ratio of microcrystalline cellulose to cellulose ether thickening agent is from 1:1 to 1:3 by weight; or from 1:1.5 to 1:2.75 by weight. In any of the above embodiments comprising sodium carboxymethylcellulose, microcrystalline cellulose may be used in combination with NaCMC. In certain such embodiments, the MCC/sodium carboxymethylcellulose may be present in an amount of from 0.5 to 1.5 weight % based on the total weight of the composition.

Abrasives

[0203] In certain embodiments the compositions of the disclosure may comprise additional calcium-containing abrasives, for example calcium phosphate abrasive, e.g., tricalcium phosphate (Ca.sub.3(PO.sub.4).sub.2), hydroxyapatite (Ca.sub.10(PO.sub.4).sub.6(OH).sub.2), or dicalcium phosphate dihydrate (CaHPO.sub.4.2H.sub.2O, also sometimes referred to herein as DiCal) or calcium pyrophosphate, and/or silica abrasives, sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite or other siliceous materials, or combinations thereof. Any silica suitable for oral care compositions may be used, such as precipitated silicas or silica gels. For example synthetic amorphous silica. Silica may also be available as a thickening agent, e.g., particle silica. For example, the silica can also be small particle silica (e.g., Sorbosil AC43 from PQ Corporation, Warrington, United Kingdom). However the additional abrasives are preferably not present in a type or amount so as to increase the RDA of the dentifrice to levels which could damage sensitive teeth, e.g., greater than 130.

[0204] Useful silica abrasive materials for preparing the oral compositions of the present invention, e.g., any of Compositions 1.0 et seq, may be obtained from Davison Chemical Division of W. R. Grace & Co. (Baltimore, Md., USA) under the tradename Sylodent VP5, as described in United States Patent Application 2012/0100193 (the contents of which are incorporated herein by reference). The physical properties of Sylodent VP5 are shown in Table 1.

TABLE-US-00002 TABLE 1 Sylodent VP5 N.sub.2 BET surface area (m.sup.2/g) <50 Oil absorption (cc/100 g) 80-100 Mean particle size (μm) 9-13 d10 (μm) 2.74 Brass Einlehner hardness 6-9 

[0205] The use of Sylodent VP5 in oral care compositions can impart a superior cleaning ability, e.g., a high PCR value, and at the same time, reduces damage to hard dental surfaces, e.g., a low RDA, as shown in United States Patent Application 2012/0100193.

Water

[0206] Water is present in the oral compositions of the invention. Water, employed in the preparation of commercial oral compositions should be deionized and free of organic impurities. Water commonly makes up the balance of the compositions and includes 5% to 45%, e.g., 10% to 20%, e.g., 25-35%, by weight of the oral compositions. This amount of water includes the free water which is added plus that amount which is introduced with other materials such as with sorbitol or silica or any components of the invention. The Karl Fischer method is a one measure of calculating free water.

Humectants

[0207] Within certain embodiments of the oral compositions, it is also desirable to incorporate a humectant to reduce evaporation and also contribute towards preservation by lowering water activity. Certain humectants can also impart desirable sweetness or flavor to the compositions. The humectant, on a pure humectant basis, generally includes 15% to 70% in one embodiment or 30% to 65% in another embodiment by weight of the composition.

[0208] Suitable humectants include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, propylene glycol as well as other polyols and mixtures of these humectants. Mixtures of glycerin and sorbitol may be used in certain embodiments as the humectant component of the compositions herein.

Amino Acids

[0209] In some aspects, Compositions 1.0 et seq can comprise a basic amino acid. The basic amino acids which can be used in the compositions and methods of the invention include not only naturally occurring basic amino acids, such as arginine, lysine, and histidine, but also any basic amino acids having a carboxyl group and an amino group in the molecule, which are water-soluble and provide an aqueous solution with a pH of 7 or greater.

[0210] For example, basic amino acids include, but are not limited to, arginine, lysine, serine, citrulline, ornithine, creatine, histidine, diaminobutanoic acid, diaminoproprionic acid, salts thereof or combinations thereof. In a particular embodiment, the basic amino acids are selected from arginine, citrulline, and ornithine. In certain embodiments, the basic amino acid is arginine, for example, L-arginine, or a salt thereof.

[0211] In another aspect, the compositions of the invention (e.g., Compositions 1.0 et seq) can further comprise one or more neutral amino acid, which can include, but is not limited to, one or more neutral amino acids selected from the group consisting of alanine, aminobutyrate, asparagine, cysteine, cystine, glutamine, glycine, hydroxyproline, isoleucine, leucine, methionine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, valine, and combinations thereof.

[0212] The compositions and methods according to the invention (e.g., Composition 1.0 et seq) can be incorporated into oral compositions for the care of the mouth and teeth such as dentifrices, toothpastes, transparent pastes, gels, mouth rinses, sprays and chewing gum.

[0213] The toothpaste making process involves sufficient mixing for a homogenous product. In some embodiments, the later part of the process (after the gel phase and once silica is added) is performed under vacuum, for example at least about −26 mmHg, to remove entrapped air bubbles that could contribute to finished product opacity.

[0214] As used throughout, ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range. In addition, all references cited herein are hereby incorporated by reference in their entireties. In the event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls. It is understood that when formulations are described, they may be described in terms of their ingredients, as is common in the art, notwithstanding that these ingredients may react with one another in the actual formulation as it is made, stored and used, and such products are intended to be covered by the formulations described.

[0215] The following examples further describe and demonstrate illustrative embodiments within the scope of the present invention. The examples are given solely for illustration and are not to be construed as limitations of this invention as many variations are possible without departing from the spirit and scope thereof. Various modifications of the invention in addition to those shown and described herein should be apparent to those skilled in the art and are intended to fall within the appended claims.

EXAMPLES

Example 1

[0216] The following are representative formulas of the present disclosure (ingredients listed as percentages by wt. of the total formulations) (*Note: tables reflect total Zn, Sn, total insoluble metals per analytical evaluation):

TABLE-US-00003 TABLE 1 Ingredients. A B C D Polymers    4%    4%    4%    4% Sweetener    2%    2%    2%    2% and Flavor Sod. Fluoride 0.243% 0.243% 0.243%  0.32% Humectant 51.83% 51.83% 51.83% 47.60% Water q. s. q. s. q. s. q. s. Silica VP5   20%   20%   20%   20% Thickener    5%  5.5%    5%    6% Anionic  1.5%  1.5%  1.5%  1.5% Surfactant Zwitterionic  1.25%  1.25%  1.25%  1.25% Surfactant (30% solution) Trisodium    3% —    3%  6.5% Citrate Citric Acid — — — — Zn Oxide  0.5%  0.5%    1%    1% Zn Citrate  1.35%  1.35%  0.5%  0.5% Arginine  1.3%  1.3%  1.3%  1.3% Total Zinc  0.82%  0.82%  0.96%  0.96% Total  0.48%  0.68%  0.7%  0.6% insoluble zinc Appearance Clear Opaque Opaque Clear % of soluble   47%   17%   27%  37.5% zinc relative to total zinc

TABLE-US-00004 TABLE 2 Ingredients H J Polymers  3.5%    4% Sweetener and    2%    2% Flavor Sod. Fluoride 0.243%  0.32% Humectant 55.87% 54.1 Water    7%    8% Silica (e.g.,   20%   20% Sylodent VP5) Thickener    5%    6% Anionic  1.5%  1.5% Surfactant Zwitterionic  1.25%  1.25% Surfactant Trisodium Citrate    2% — Citric Acid  0.1% — Zn Oxide  0.5%    1% Zn Citrate —  0.5% Arginine —  1.3% Total Zinc  0.43%  0.96% Total insoluble  0.31%  0.84% zinc Appearance Clear Opaque % of soluble zinc   28%  12.5% relative to total zinc

[0217] Further representative formulas containing both zinc and stannous ion sources:

TABLE-US-00005 TABLE 3 Ingredients. N O P Q Polymers    4%    4%    4%    4% Flavor and    2%    2%    2%    2% Sweetener Stannous 0.454% 0.454% 0.454% 0.454% Fluoride Humectant 52.27% 54.77% 54.57%   50% Water q.s. q.s. q.s. q.s. Silica   20%   20%   20%   20% (Sylodent VP5) Thickener    5%    5%    5%  5.25% Anionic  1.5%  1.5%  1.5%  1.5% Surfactant Zwitterionic  1.25%  1.25%  1.25%  1.25% Surfactant Trisodium    3%  3.5% —    4% Citrate Citric Acid —  0.1% — — Alkali    1%  1.2%  1.2%  1.8% Phosphate Salt Zn Oxide — — — — Zinc Citrate    1% — — — Zinc —    1%    1%    1% Phosphate Potassium  0.5% — — — Nitrate Arginine — — — — Total Zinc 0.32 0.45 0.45 0.44 Total Tin 0.35 0.35 0.35 0.35 Total  0.14%  0.23%  0.33%  0.18% Insoluble Zinc Total 0.01 0.04 0.14 0.07 Insoluble Tin Total Metal 0.67 0.8  0.8  0.79 Total  0.15%  0.27% 0.47 0.25 Insoluble Metal Appearance Clear Clear Opaque Clear % of soluble  77.4%   66%   41%   68% metal (zinc and stannous) relative to total metal

[0218] Insoluble zinc (and stannous) were determined for each formula by subtracting soluble metal analytical results from total zinc (and stannous) analytical results.

Example 2

[0219] An in-vitro Plaque Glycolysis model was utilized to compare antibacterial efficacy of toothpaste formulations containing significantly different levels of soluble metal. The study details are as follows.

[0220] Plaque glycolysis Model: An in-vitro adaptation of a published Plaque Glycolysis Model (Donald J. White, et. al., Journal of Clinical Dentistry, #6 Special Issue, Pp 69-78, 1995) was used to indirectly measure biofilm health. Briefly, the method quantifies the glycolytic effects of toothpaste formulas on treated in vitro biofilm pool of both anaerobic and aerobic bacteria. The efficacy of each toothpaste formula is based on biofilm pH change. A lower average pH change indicates reduction of viable bacteria and greater antibacterial performance of the respective test toothpaste. Finally, in these studies, an untreated cell is used as the negative control.

[0221] In one test (Table 4 below), two common formulations containing the same total zinc metal but different levels of soluble zinc are compared (Formulas A & B from Example 1 above). It can be seen that sample A with 3% trisodium citrate and 47% of the zinc in a soluble state provides significantly greater reduction in viable bacteria compared to the common Formula B. Formula B, as the main point of difference to formula A, does not contain trisodium citrate and contains only 17% of the zinc in a soluble state.

TABLE-US-00006 TABLE 4 Plaque Glycolysis Study—Average pH Change with Treatment (Test 1) Statistical Sample Avg pH Change Comparison* Untreated** 2.519 +/− 0.095 A Toothpaste B 0.882 +/− 0.033 B Toothpaste A 0.529 +/− 0.048 C *Means that don't share common letter = Sign. Diff @95% CI, Tukey method, N = 3 per cell. **Negative Control, untreated biofilm

[0222] In a second plaque glycolysis test, two other common formulations containing the same total zinc metal but different levels of soluble zinc are compared (Formulas C & D from Example 1). The results are shown in Table 5 below. Again, it was observed that the toothpaste (D) with 37.5% of the zinc in soluble form provides greater reduction in viable bacteria compared to the toothpaste C with only 27% of soluble zinc relative to total zinc. Again, the difference in performance is statistically significant and indicates that more soluble metal typically provides improved antibacterial performance in an otherwise equivalent formulation.

TABLE-US-00007 TABLE 5 Plaque Glycolysis Study: Average pH Change with Treatment (Test 2) Statistical Sample Avg pH Change Comparison* Untreated** 2.622 +/− 0.078 A Toothpaste C 0.712 +/− 0.024 B Toothpaste D 0.603 +/− 0.037 C *Means that don't share common letter = Sign. Diff @95% CI, Tukey method, N = 3 per cell. **Negative Control, untreated biofilm.

[0223] In a third plaque glycolysis test, two formulations are compared that have a common base with the same target levels of total stannous and zinc metals but demonstrate different soluble metal levels by means of analytical evaluations (Formulas O & P from Example 1). The results are shown in Table 6 below. The higher soluble metal in Formula O is due to inclusion of 3.5% trisodium citrate which Formula P does not contain. Again, the difference in performance is statistically significant and indicates that more soluble metal typically provides improved antibacterial performance in an otherwise equivalent formulation.

TABLE-US-00008 TABLE 6 Plaque Glycolysis Study—Average pH Change with Treatment (Test 3) Statistical Sample Avg pH Change Comparison* Untreated** 2.743 +/− 0.092 A Toothpaste P 0.916 +/− 0.067 B Toothpaste O 0.579 +/− 0.052 C *Means that don't share common letter = Sign. Diff @95% CI, Tukey method, N = 3 per cell. **Negative Control, untreated biofilm.

Example 3

[0224] Determination of Gel Transparency

[0225] Determination of gel transparency was determined by subjective visual measurements, wherein a ribbon of toothpaste is squeezed onto a sheet of white paper containing typed text. The samples are rated on a rating scale of 1 to 10, where a 10 is given if the text can be read perfectly, a score of 1 is given when the text cannot be seen and intermediate scores of 2 to 9 are given for progressively better clarity of the text. A minimum score of 8 is deemed a clear gel toothpaste.

[0226] In addition, a select set of samples were also evaluated for turbidity and transmittance according to the method reported in International Patent Publication No. WO2021002910A1, incorporated herein in its entirety, to correlate subjective assessments with analytical measurements. Turbidity for the tested toothpastes are tested on a Hach-2100Q portable turbidimeter. Turbidity is expressed on a scale from 0 to 1000 NTU, wherein 0 represents complete optical clarity. Transmittance for the toothpastes is tested on a Turbiscan LAB stability analyzer as percent of light transmitted (100% is optical clarity). The results are shown in Table 7 below. It should be noted that both turbidity and transmittance are dependent on the path length through the sample tested (turbidity and transmittance being linearly proportional to path length for homogenous samples) and while visual measurements were made on the dentifrice ribbon squeezed out of a toothpaste tube with an approximate thickness of 7-10 mm, the instruments used require filling a sample cube having a 24.8 mm path length with the tested toothpaste. As a result, values obtained for transmittance and turbidity are depressed compared to the values that would be achieved in practice, and should be considered for best correlation to visual impact.

TABLE-US-00009 TABLE 7 Turbidity & Transmittance Measurements of Toothpaste Gels Formulas of Example 1 (only zinc) A B C D H J Visual Clarity (10 = very 10 3 4 8 8 1 clear, l = very opaque) Turbidity (0-1000NTU) 83 357 323 138 — 998 Transmittance (%) 24 9 11 19 — 1.2 Formulas of Example 1 (both zinc and stannous) N O P Q Visual Clarity (10 = very 9 8 2 8 clear, l = very opaque) Turbidity (0-1000NTU) — 146 923 — Transmittance (%) — 22 3.8 —

[0227] The results show that Formulas A, D, H, N, O and Q, having the higher values for % of soluble metal (zinc, or zinc and stannous) relative to total metal have surprisingly high levels of clarity and transparency. In contrast, Formulas B, C, J and P have substantially lower clarity and transparency.

Example 4

[0228] Refractive Index of Sylodent VP5 Silica

[0229] The refractive index of 4% Sylodent VP5 Silica in water/sorbitol solutions was determined using a Spectronic 21D Spectrophotometer at 589 nm wavelength (refractometer range=1.435-1.52). The % Transmittance of VP5 Silica solutions, and also two other commercially available high cleaning silicas was determined using a Shimadzu UV-1601PC Spectrophotometer, also at 589 nm wavelength. The results are shown in Table 8 below.

TABLE-US-00010 TABLE 8 Refractive Index and % Transmittance of Silica % Transmittance Sorbitol/ Other High Other High % Sorbitol Water Water No VP5 Cleaning Cleaning Sorbitol Wt (g) Wt (g) R.I. Silica Silica Silica #1 Silica #2 Sol'n 50 100 100 ID 60 120 80 70 140 60 A 80 160 40 — 99.85 4.48 8.84 8.86 B 85 170 30 1.439 99.88 15.21 27.31 24.18 C 87 174 26 1.442 99.98 24.35 46.80 40.09 D 90 180 20 1.446 100.48 38.33 70.10 68.38 E 93 186 14 1.451 100.06 88.02 89.89 94.65 F 95 190 10 1.454 99.04 94.64 76.99 95.50 97 194 6 100 200 0 Note: Spectronic 21D Spectrophotometer, 589 nm wavelength/used for refractive index Refractometer range = 1.435-1.52 Note: Shimadzu UV-1601PC Spectrophotometer, 589 nm wavelength/used for % Transmittance

[0230] It has been discovered in accordance with the present invention that both the refractive index (RI) of the gel phase (humectants, water, surfactants and in some cases flavor) and the RI of silicas in the formulation should closely match. Sylodent VP5 Silica is unique in that it is one of a very few high cleaning silicas with a desirable RI that provides effective clarity with a metal-containing toothpaste, particularly where the metals are sufficiently solubilized as described herein. Thus, the formulations of the present disclosure utilizing tri sodium citrate and other materials to improve metal solubility provide transparent gels that also boost antibacterial performance.