COMPOSITIONS FOR ORAL CARE AND METHODS OF USE.

Abstract

This invention relates to oral care compositions comprising guanidine, zinc citrate, zinc oxide, and a fluoride source, as well as to methods of use and manufacture of these compositions.

Description

COMPOSITIONS FOR ORAL CARE AND METHODS OF USE This application claims priority over U.S. provisional application No. 63 / 000,744, filed on March 27, 2020, the contents of which are incorporated herein by reference in their entirety. FIELD OF INVENTION This invention relates to oral care compositions comprising guanidine in free form or as an orally acceptable salt, zinc oxide and zinc citrate, and a source of fluoride, as well as to methods of use and manufacture of these compositions. BACKGROUND OF THE INVENTION Oral care compositions present particular challenges for the prevention of microbial contamination. Zinc is a well-known antimicrobial agent used in toothpaste formulations. At effective concentrations, zinc has been shown to inhibit bacterial glycolysis and bacterial protease activity. Zinc is also a well-known essential mineral for human health, and it has been shown to help strengthen tooth enamel and promote cell repair. Unfortunately, conventional toothpaste formulations often require high concentrations of zinc, for example, 2% by weight or more, to achieve efficacy. At this concentration, zinc imparts a noticeably astringent taste to the formulation. There is, therefore, a need for improved antibacterial toothpaste formulations that do not suffer from the drawbacks of conventional compositions. BRIEF DESCRIPTION OF THE INVENTION Not limited to theory, the addition of guanidine in free or salt form could provide a way to efficiently deliver one or more antimicrobial agents, such as zinc, to oral cavity biofilms. Consequently, current formulations offer the advantage of robust microbial protection without significantly interfering with the stability of the oral care composition, allowing for formulations that use less zinc and / or improve the delivery of zinc ions to the biofilm in the oral cavity. Without limiting itself to any particular theory, it is believed that the presence of guanidine may help increase the amount of soluble zinc, which could then enhance the effect of inhibiting bacterial growth in a user's oral cavity. In one aspect, the invention is an oral care composition (Composition 1.0) comprising: a. guanidine, in free or salt form; b. zinc oxide and zinc citrate; c. a source of fluoride (for example, sodium fluoride) MA / a / zuzz / ui io / z For example, the invention contemplates any of the following compositions (unless otherwise stated, values ​​are given as a percentage of the overall weight of the composition) 1.1 Composition 1.0 where guanidine is in free form. 1.2 Composition 1.0, wherein the guanidine is partially or completely in salt form. 1.3 Any of the above compositions wherein guanidine (e.g., guanidine HCl) is present in an amount corresponding to 0.3% to 15%, (e.g., 0.04 wt. to 3 wt. of the total weight of the composition), (e.g., approximately 0.45%), (e.g., approximately 0.9%), (e.g., approximately 1.5%), (e.g., approximately 1.8 wt.). 1.4 Any of the above compositions wherein guanidine is present from 0.1% by weight - 5.0% by weight (e.g., approximately 0.45%, 0.9% or 1.8% by weight). 1.5 Any of the above compositions, wherein guanidine is present at approximately 0.45% by weight of the total weight of the composition. 1.6 Any of the above compositions, wherein guanidine is present at approximately 0.9% by weight of the total weight of the composition. 1.7 Any of the above compositions, wherein guanidine is present at approximately 1.5% by weight of the total weight of the composition. 1.8 Any of the above compositions, wherein guanidine is present at approximately 1.8% by weight of the total weight of the composition. 1.9 Any of the above compositions, wherein guanidine is a salt selected from the group consisting of: guanidine hydrochloride, guanidine monohydrate, guanidine monohydrobromide, guanidine monohydrochloride, guanidine monohydroiodide, guanidine nitrate, guanidine phosphate, guanidine sulfate, guanidinium chloride and combinations thereof. 1.10 The above composition, wherein the guanidine salt is guanidine hydrochloride. 1.11 Any of the above compositions, wherein the guanidine is in the oral care compositions in the form of guanidinium (e.g., the conjugated acid). 1.12 Any of the above compositions, wherein the guanidine is ionized by neutralization with an acid or a salt of an acid. 1.13 Any of the above, wherein the weight of guanidine refers to the weight of the salt (e.g., guanidine HCl) relative to the total weight of the composition. 1.14 Any of the above compositions, wherein the composition does not contain ethanol. 1.15 Any of the above compositions further comprising a fluoride source selected from: tin fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (for example, N' octadecyltrimethylethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof. 1.16 Any of the above compositions, wherein the fluoride source is a fluorophosphate. 1.17 Any of the above compositions, wherein the source of fluoride is sodium monofluorophosphate. 1.18 Any of the above compositions, wherein the source of fluoride is sodium fluoride. 1.19 Any of the above compositions, wherein the source of fluoride is tin fluoride. 1.20 Any of the above compositions, wherein the source of fluoride is a fluoride salt present in an amount of 0.1% by weight to 2% by weight (0.1% by weight - 0.6% by weight) of the total weight of the composition (e.g., sodium fluoride (e.g., approximately 0.3% by weight) or sodium monofluorophosphate). 1.21 Any of the above compositions, wherein the fluoride source is a soluble fluoride salt providing fluoride ions in an amount of 50 to 25,000 ppm (e.g., 750-2,000 ppm, e.g., 1,000-1,500 ppm, e.g., approximately 1,000 ppm, e.g., approximately 1,450 ppm) 1.22 Any of the above compositions, wherein the source of fluoride is sodium fluoride providing fluoride in an amount of 750 - 2,000 ppm (e.g., approximately 1,450 ppm) 1.23 Any of the above compositions, wherein the fluoride source is selected from sodium fluoride and sodium monofluorophosphate and this provides fluoride in an amount of 1,000 ppm - 1,500 ppm. 1.24 Any of the above compositions, wherein the source of fluoride is sodium fluoride or sodium monofluorophosphate and this provides fluoride in an amount of approximately 1,450 ppm. 1.25 Any of the above compositions, where the pH is between 7.5 and 10.5, for example from 9.0 to 10.0, for example, 9.4. 1.26 Any of the above compositions, further comprising calcium carbonate. 1.27 The composition of 1.26, wherein the calcium carbonate is a highly absorbent precipitated calcium carbonate (e.g., 20% to 30% by weight of the composition) (e.g., 25% highly absorbent precipitated calcium carbonate). 1.28 The composition of 1.27, further comprising a precipitated calcium carbonate - light (e.g., approximately 10% precipitated calcium carbonate - light) (e.g., approximately 10% natural calcium carbonate). 1.29 Any of the above compositions, further comprising an effective amount of one or more alkali phosphate salts, for example, sodium, potassium or calcium salts, for example, selected from alkali dibasic phosphate and alkali pyrophosphate salts, for example, alkali phosphate salts selected from sodium dibasic phosphate, potassium dibasic phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, disodium hydrogen orthophosphate, monosodium phosphate, pentapotassium triphosphate and mixtures of any two or more of them, for example, in an amount of 1-20%, for example, 2-8%, for example, ca. 5%, by weight of the composition. 1.30 The composition of 1.29, wherein the tin salt is selected from tin fluoride, tin pyrophosphate and combinations thereof. 1.31 Any of the above compositions, comprising tetrapotassium pyrophosphate, disodium hydrogen orthophosphate, monosodium phosphate, and pentapotassium triphosphate. 1.32 Any of the above compositions, comprising a polyphosphate. 1.33 The composition of 1.32, wherein the polyphosphate is tetrasodium pyrophosphate. 1.34 The composition of 1.33, wherein tetrasodium pyrophosphate is 0.1 - 1.0% by weight (for example, approximately 0.5% by weight). 1.35 Any of the above compositions, further comprising an abrasive or particles (e.g., silica). 1.36 Any of the above compositions, wherein the silica is synthetic amorphous silica (e.g., 1% - 25% by weight) (e.g., 8% - 25% by weight) 1.37 Any of the above compositions, wherein the silica abrasives are silica gels or precipitated amorphous silicas, e.g. silicas having an average particle size ranging from 2.5 microns to 12 microns. 1.38 Any of the above compositions, further comprising a small silica particle with an average particle size (d50) of 1-5 microns (e.g., 3-4 microns) (e.g., approximately 5 wt% of Sorbosil AC43 from Ineos Silicas, Warrington, UK). 1.39 Any of the above compositions wherein 20-30% by weight of the total silica in the composition is small particle silica (e.g., having an average particle size (d50) of 3-4 microns) and wherein the small particle silica is approximately 5% by weight of the oral care composition. 1.40 Any of the above compositions comprising silica, wherein the silica is used as a thickening agent, e.g., particulate silica. 1.41 Any of the above compositions further comprising a non-ionic surfactant, wherein the non-ionic surfactant is in an amount of 0.5-5%, for example, 1-2%, selected from poloxamers (for example, poloxamer 407), polysorbates (for example, polysorbate 20), polyoxyl hydrogenated castor oil (for example, polyoxyl hydrogenated castor oil 40), and mixtures thereof. 1.42 Any of the above compositions, wherein the non-ionic surfactant poloxamer has a polyoxypropylene molecular mass of 3,000 to 5,000 g / mol and a polyoxyethylene content of 60 to 80 mol%, for example, the non-ionic surfactant poloxamer comprises poloxamer 407. 1.43 Any of the above compositions, further comprising sorbitol, wherein the sorbitol is in a total amount of 10-40% (for example, approximately 23%). 1.44 Any of the above compositions wherein the ratio of the amount of zinc oxide (e.g., wt. %) to zinc citrate (e.g., wt. %) is from 1.5:1 to 4.5:1 (e.g., 2:1, 2.5:1, 3:1, 3.5:1, or 4:1). 1.45 Any of the above compositions wherein zinc citrate is present in an amount of 0.25 to 0.75% by weight (e.g., 0.5% by weight) and zinc oxide may be present in an amount of 0.75 to 1.25% by weight (e.g., 1.0% by weight) based on the weight of the oral care composition. 1.46 Any of the above compositions, wherein zinc citrate is approximately 0.5% by weight. 1.47 Any of the above compositions, wherein zinc oxide is approximately 1.0% by weight. 1.48 Any of the above compositions wherein zinc citrate is approximately 0.5% by weight and zinc oxide is approximately 1.0% by weight. 1.49 Any of the above compositions, further comprising a preservative selected from: benzyl alcohol, methylisothiazolinone (MIT), sodium bicarbonate, sodium methyl cocoyl taurate (tauranol), lauryl alcohol, and polyphosphate. 1.50 The composition of 1.49, wherein benzyl alcohol is present from 0.1 - 0.6% by weight, (for example, 0.1 - 0.4% by weight) for example, approximately 0.1% by weight, approximately 0.2% by weight or approximately 0.3% by weight. 1.51 The composition of 1.50, wherein benzyl alcohol is approximately 0.1% by weight. 1.52 Any of the above compositions comprising polymer films. 1.53 Any of the above compositions comprising flavoring, fragrance and / or coloring. 1.54 The composition of 1.53, wherein the flavoring agent is sodium saccharin, sucralose, or one of their mixtures. 1.55 Any of the above compositions, wherein the composition comprises thickening agents selected from the group consisting of carboxyvinyl polymers, carrageenan, hydroxyethylcellulose and water-soluble salts of cellulose ethers (for example, sodium carboxymethylcellulose and sodium carboxymethyl hydroxyethylcellulose). 1.56 Any of the above compositions, wherein the composition comprises sodium carboxymethylcellulose (for example, from 0.5% by weight - 1.5% by weight) 1.57 Any of the above compositions comprising 5% - 40%, for example, 10% iviA / a / zuzz / uiio / z - 35%, for example, approximately 15%, 25%, 30%, and 35% water. 1.58 Any of the above compositions comprising an additional antibacterial agent selected from halogenated diphenyl ether (e.g., triclosan), herbal extracts and essential oils (e.g., rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitiol, catechol, methyl salicylate, epigallocatechin gallate, gallate, gallic acid, miswak extract, sea buckthorn extract), bisguanide antiseptics (e.g., chlorhexidine, alexidine, or octenidine), quaternary ammonium compounds (e.g., cetylpyridinium chloride (CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), antiseptics phenolics, hexetidine, octenidine, sanguinarine, povidone-iodine, delmopinol, salifluorine, metal ions (e.g., zinc salts, e.g., zinc chloride, zinc lactate, zinc sulfate, tin salts, copper salts,iron salts), sanguinarine, propolis and oxygenating agents (for example, hydrogen peroxide, buffered sodium peroxyborate or peroxycarbonate), italic acid and its salts, monoperthalic acid and its salts and esters, ascorbyl stearate, oleoyl sarcosine, alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domiphene bromide, delmopinol, octapinol and other piperidine derivatives, niacin preparations, chlorite salts; and mixtures of any of the foregoing. 1.59 Any of the above compositions comprising an antioxidant, for example, selected from the group consisting of Coenzyme Q10, PQQ, Vitamin C, Vitamin E, Vitamin A, BHT, anethole-dithiothione, and mixtures thereof. 1.60 Any of the above compositions comprising a bleaching agent. 1.61 Any of the above compositions, comprising a bleaching agent selected from a bleaching active selected from the group consisting of peroxides, metallic chlorites, perborates, percarbonates, peroxyacids, hypochlorites, and combinations thereof. 1.62 Any of the above compositions, further comprising hydrogen peroxide or a source of hydrogen peroxide, for example, urea peroxide or a peroxide salt or complex (for example, such as peroxyphosphate, peroxycarbonate, perborate, peroxysilicate, or persulfate salts, for example, calcium peroxyphosphate, sodium perborate, sodium carbonate peroxide, sodium peroxyphosphate and potassium persulfate), or hydrogen peroxide polymer complexes such as hydrogen peroxide-polyvinylpyrrolidone polymer complexes. 1.63 Any of the above compositions further comprising an agent that interferes with or prevents bacterial binding, e.g., ELA or chitosan. 1.64 Any of the above compositions, further comprising a basic amino acid. 1.65 The composition of 1.64, wherein the basic amino acid is selected from: arginine, lysine, serine, citrulline, ornithine, creatine, histidine, diaminobutanoic acid, diaminoproprionic acid, salts thereof or combinations thereof. 1.66 Any of the above compositions, wherein the oral care composition is a toothpaste comprising a zwitterionic surfactant, for example a betaine surfactant, for example cocamidopropyl betaine, for example in an amount of approximately 0.1% to approximately 4.5% by weight, for example 0.5-2% cocamidopropyl betaine by weight of the composition 1.67 Any of the above compositions, comprising: a. approximately 0.5%-1.5% of zinc oxide by weight of the total composition. b. approximately 0.25% - 0.75% of zinc citrate by weight of the total composition c. approximately 0.2% - 2.5% guanidine by weight of the total composition d. from 700 ppm to 1,500 ppm (for example, 1,450 ppm) of sodium fluoride. 1.68 Any of the above compositions, comprising: a. approximately 1.0% zinc oxide b. approximately 0.5% zinc citrate c. approximately 0.45% guanidine d. from 700 ppm to 1,500 ppm (for example, 1,450 ppm) of sodium fluoride. 1.69 Any of the above compositions, comprising: a. approximately 1.0% zinc oxide b. approximately 0.5% zinc citrate c. approximately 0.9% guanidine d. from 700 ppm to 1,500 ppm (for example, 1,450 ppm) of sodium fluoride. 1.70 Any of the above compositions, comprising: a. approximately 1.0% zinc oxide b. approximately 0.5% zinc citrate c. approximately 1.5% guanidine d. from 700 ppm to 1,500 ppm (for example, 1,450 ppm) of sodium fluoride. 1.71 Any of the above compositions, comprising: a. approximately 1.0% zinc oxide b. approximately 0.5% zinc citrate c. approximately 1.8% guanidine d. from 700 ppm to 1,500 ppm (for example, 1,450 ppm) of sodium fluoride. 1.72 Any of the above compositions is effective after application in the oral cavity, for example, by rinsing, optionally in conjunction with brushing, to (i) reduce or inhibit the formation of dental caries, (ii) reduce, repair or inhibit pre-carious enamel lesions, for example, as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM), (iii) reduce or inhibit demineralization and promote remineralization of teeth, (iv) reduce tooth hypersensitivity, (v) reduce or inhibit gingivitis, (vi) promote healing of mouth sores or cuts, (vii) reduce levels of acid-producing bacteria, (viii) inhibit the formation of microbial biofilm in the oral cavity, (ix) raise and / or maintain plaque pH at levels of at least pH 5.5 followed by the sugar challenge, (x) reduce plaque buildup, (xi) treat, relieve or reduce dry mouth, (xii) clean teeth and oral cavity, (xiii) reduce erosion, (xiv) prevent staining and / or whiten teeth, (xv) immunize teeth against cariogenic bacteria; and / or (xvi) promote systemic health, including cardiovascular health, for example by reducing the potential for systemic infection through oral tissues. 1.73 Any of the above oral compositions, wherein the oral composition may be any of the following oral compositions selected from the group consisting of: a toothpaste or dentifrice, a mouthwash or mouth rinse, a topical oral gel, and a denture cleaner. 1.74 A composition is obtained or can be obtained by combining the ingredients as set out in any of the above compositions. 1.75 A composition of any of the above compositions further comprising an amino acid (for example, arginine) 1.76 A composition of any of Composition 1.0 - 1.74, wherein the guanidine is in the form of a free or orally acceptable salt and is not present as a moiety in one or more larger organic molecules. 1.77 The above composition wherein guanidine is present in the form of a free or orally acceptable salt and the composition does not comprise an amino acid (e.g., arginine). 1.78 The above composition, wherein the composition does not comprise arginine. 1.79 A composition of 1.78, wherein the composition comprises: a. approximately 0.5% - 1.5% zinc oxide by weight of the total composition. b. approximately 0.25% - 0.75% of zinc citrate by weight of the total composition c. approximately 0.2% - 2.5% guanidine by weight of the total composition of 700 ppm to 1,500 ppm (e.g., 1,450 ppm) of sodium fluoride; and wherein the guanidine is in the form of a free or orally acceptable salt and is not present in the composition as a moiety in one or more larger organic molecules (e.g., arginine). 1.80 A composition is obtained or can be obtained by combining the ingredients as set out in any of the above compositions. 1.81 A composition for use as set forth in any of the above compositions. In another embodiment, the invention encompasses a method for improving oral health comprising applying an effective amount of the oral composition of any of Composition 1.0 and following, as previously established, to the oral cavity of a subject in need, for example, a method for i. reduce or inhibit the formation of dental caries, ii. reduce, repair, or inhibit early enamel lesions, e.g., as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM), iii. reduce or inhibit demineralization and promote remineralization of teeth, iv. reduce tooth hypersensitivity, v. reduce or inhibit gingivitis, vi. promote the healing of mouth sores or cuts, vii. reduce levels of acid-producing bacteria, vili. inhibit the formation of microbial biofilm in the oral cavity, ix. raise and / or maintain plaque pH at levels of at least pH 5.5 following sugar challenge, x. reduce plaque accumulation, xi. treat dry mouth, xii. enhance systemic health, including cardiovascular health, e.g., by reducing the potential for systemic infection through oral tissues, xiii. teeth whitening, xiv.reduce tooth erosion, xv. immunize (or protect) teeth against cariogenic bacteria and their effects, and / or xvi. clean teeth and the oral cavity. The invention further comprises the use of sodium bicarbonate, sodium methyl cocoyl taurate (tauranol), MIT, and benzyl alcohol and combinations thereof in the manufacture of a Composition of the invention, for example, for use in any of the indications set forth in the preceding method of Composition 1.0, and following. DETAILED DESCRIPTION OF THE INVENTION As used herein, the term toothpaste means paste, gel, or liquid formulations unless otherwise specified. The toothpaste composition may be in any desired form, such as deep strips, shallow strips, multi-layered, having a gel surrounding the paste, or any combination thereof. Alternatively, the oral composition may be dispensed in a dual-phase from a separate-compartment dispenser. As used herein, the term “guanidine” refers to the compound with the formula HNC(NH2)2 in its free or salt form. The conjugate acid of guanidine is the guanidinium cation, (C(NH2)3+). Guanidine derivatives may exist as salts containing the conjugate acid. Guanidine is a very strong base in water. In neutral water, a person skilled in the art will understand that guanidine will most likely exist as guanidinium. A person skilled in the art will understand the circumstances in which guanidine exists in the formulation in the form of protonated guanidinium. MA / a / ZUZZ / UI lOfZ Guanidine, as used herein, may refer, for example, to guanidine or guanidinium, or a salt thereof. Physiologically acceptable salts include those derived from pharmaceutically acceptable inorganic or organic acids or bases, for example, acid addition salts formed from acids that form a physiologically acceptable anion, such as the hydrochloride or bromide salt, and base addition salts formed from bases that form a physiologically acceptable cation, such as those derived from alkali metals such as potassium and sodium or alkaline earth metals such as calcium and magnesium. Physiologically acceptable salts may be obtained by the use of standard procedures known in the art. As used herein, an oral care composition refers to a composition whose intended use includes oral care, oral hygiene, and / or oral appearance, or whose intended method of use involves administration to the oral cavity, and refers to compositions that are palatable and safe for topical administration to the oral cavity and that provide a benefit to the teeth and / or oral cavity. The term “oral care composition” therefore specifically excludes compositions that are highly toxic, unpalatable, or otherwise unsuitable for administration to the oral cavity. In some embodiments, an oral care composition is not intentionally ingested but is retained in the oral cavity for a sufficient time to induce the intended benefit.Oral care compositions as described herein can be used in non-human mammals such as companion animals (e.g., dogs and cats), as well as in humans. In some embodiments, humans use the oral care compositions as described herein. Oral care compositions include, for example, toothpaste and mouthwash. In some embodiments, the description provides mouthwash formulations. As used herein, “orally acceptable” refers to a material that is safe and palatable at concentrations relevant for use in an oral care formulation, such as a mouthwash or toothpaste. As used herein, “orally acceptable carrier” refers to any vehicle useful for formulating the oral care compositions described herein. An orally acceptable carrier is not harmful to a mammal in the quantities described herein when held in the mouth, without being ingested, for a period sufficient to permit effective contact with a tooth surface as required herein. In general, an orally acceptable carrier is not harmful even if accidentally ingested. 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 flavoring, a pigment, a dye, an anticaries agent, an antibacterial agent, a bleaching agent, a desensitizing agent, a vitamin, a preservative, an enzyme, and mixtures thereof. Amino acid In some respects, any of Compositions 1.0 and following may include a basic or neutral amino acid. The basic amino acids that may 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 acid having both a carboxyl and an amino group in the molecule, being water-soluble, and providing an aqueous solution with a pH of 7 or higher. 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 one particular formulation, the basic amino acids are selected from arginine, citrulline, and ornithine. In certain forms, the basic amino acid is arginine, for example, L-arginine or a salt thereof. In another aspect, the compositions of the invention (for example, any of Compositions 1.0 and following) may include a neutral amino acid, which may 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. The compositions of the invention are designed for topical use in the mouth, and likewise, the salts for use in the present invention must be safe for such use, in the amounts and concentrations provided. Suitable salts include salts known in the art to be pharmaceutically acceptable salts generally considered physiologically acceptable in the amounts and concentrations provided. Physiologically acceptable salts include those derived from pharmaceutically acceptable inorganic or organic acids or bases, for example, acid addition salts formed from acids that form a physiologically acceptable anion, for example, the hydrochloride or bromide salt, and base addition salts formed from bases that form a physiologically acceptable cation, for example, those derived from alkali metals such as potassium and sodium or alkaline earth metals such as calcium and magnesium.Physiologically acceptable salts can be obtained by using standard procedures known in the art, for example, by reacting a sufficiently basic compound such as an amine with a suitable acid that provides a physiologically acceptable anion. Fluoride ion source Oral care compositions may also include one or more sources of fluoride ions, for example, soluble fluoride salts. A wide variety of fluoride ion-producing materials can be used as soluble fluoride sources in these compositions. Examples of suitable fluoride ion-producing materials are found in the Patent of the MA / a / zuzz / ui io / z United States Patent No. 3,535,421, to Briner et al.; United States Patent No. 4,885,155, to Parran, Jr. et al.; and United States Patent No. 3,678,154, to Widder et al., each of which is 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, and mixtures thereof.When the formulation comprises calcium salts, the fluoride salts are preferably salts in which the fluoride is covalently bonded to another atom, for example, as in sodium monofluorophosphate, rather than merely bonded ionically, for example, as in sodium fluoride. Surfactants The invention may, in some embodiments, contain anionic surfactants, for example, the Compositions of Composition 1.0 and following, for example, water-soluble salts of higher fatty acid monosulfates, such as the sodium salt of the fatty acid monosulfate of hydrogenated coconut oil, such as sodium N-methyl N-cocoyl taurate, sodium coco-glyceride sulfate; higher alkyl sulfates, such as sodium lauryl sulfate; higher alkyl ether sulfates, for example of formula CH3(CH2)mCH2(OCH2CH2)nOSO3X, wherein m is 6-16, for example 10, n is 1-6, for example 2, 3 or 4, and X is Na or, for example, sodium laureth-2 sulfate (CH3(CH2)ioCH2(OCH2CH2)2CSO3Na); higher alkyl aryl sultanates, such as sodium dodecylbenzenesulfonate (sodium laurylbenzenesulfonate); higher alkyl sulfoacetates, such as sodium lauryl sulfoacetate (sodium dodecyl sulfoacetate), higher fatty acid esters of 1,2 dihydroxypropane sulfonate, sulfocolaurate (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl sarcosinate.Higher alkyl means, for example, C6-3O alkyl. In certain embodiments, the anionic surfactant (where present) is selected from sodium lauryl sulfate and sodium lauryl ether sulfate. When present, the anionic surfactant is present in an amount that is effective, for example, >0.001% by weight of the formulation, but not at a concentration that would be irritating to oral tissue, for example, 1%, and the optimum concentrations depend on the particular formulation and the particular surfactant. In one embodiment, the anionic surfactant is present from 0.03% to 5% by weight, for example, 1.5%. In another embodiment, the cationic surfactants useful in the present invention can be broadly defined as derivatives of quaternary aliphatic ammonium compounds having a long alkyl chain containing 8 to 18 carbon atoms, such as lauryltrimethylammonium chloride, cetylpyridinium chloride, cetyltrimethylammonium bromide, diisobutylphenoxyethyldimethydrylammonium chloride, cocoalkyltrimethylammonium nitrite, cetylpyridinium fluoride, and mixtures thereof. Illustrative cationic surfactants are the quaternary ammonium fluorides described in U.S. Patent No. 3,535,421 to Brinery et al., which is incorporated herein by reference. Certain cationic surfactants may also act as germicides in the compositions. The nonionic surfactants illustrative of Composition 1.0 and following, which may be used in the compositions of the invention, can be broadly defined as compounds produced by the condensation of alkylene oxide groups (of a hydrophilic nature) with a hydrophobic organic compound, which may be aliphatic or alkylaromatic in nature. Examples of suitable nonionic surfactants include, but are not limited to, pluronics, polyethylene oxide condensates of alkyl phenols, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylenediamine, 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 one particular embodiment, the composition of the invention comprises a non-ionic surfactant selected from polaxamers (e.g., polaxamer 407), polysorbates (e.g., polysorbate 20), polyoxyl hydrogenated castor oils (e.g., polyoxyl hydrogenated castor oil 40), and mixtures thereof. In yet another formulation, amphoteric surfactants may be used. Suitable amphoteric surfactants include, but are not limited to, derivatives of Ce-2 aliphatic secondary and tertiary amines that have an anionic group such as carboxylate, sulfate, sulfonate, phosphate, or phosphonate. A suitable example is cocoamidopropyl betaine. One or more surfactants are optionally present in a total amount of 0.01 wt to 10 wt, for example, 0.05 wt to 5 wt or 0.1 wt to 2 wt of the total weight of the composition. The surfactant or mixtures of compatible surfactants can be present in the compositions of the present invention from 0.1% to 5%, in another embodiment from 0.3% to 3% and in another embodiment from 0.5% to 2% by weight of the total composition. Flavoring agents The oral care compositions of the invention may also include a flavoring agent. The flavoring agents used in the practice of the present invention include, but are not limited to, essential oils and various aldehydes, esters, flavoring alcohols, and similar materials, as well as sweeteners such as sodium saccharin. Examples of essential oils include oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Chemicals such as menthol, carvone, and anethole are also useful. Certain embodiments employ peppermint and spearmint oils. The flavoring agent is incorporated into the oral composition at a concentration of 0.01 to 1% by weight. Chelating and anti-tartar agents The oral care compositions of the invention may also include one or more chelating agents capable of forming complexes with calcium found in bacterial cell walls. The binding of this calcium weakens the bacterial cell wall and increases bacterial lysis. Another group of agents suitable for use as chelating or anti-tartar agents in the present invention are soluble pyrophosphates. The pyrophosphate salts used in the present compositions may be any of the alkali metal pyrophosphate salts. In certain embodiments, the salts include alkali tetrametal pyrophosphate, alkali dimetal diacid pyrophosphate, alkali trimetal monoacid pyrophosphate, and mixtures thereof, wherein the alkali metals are sodium or potassium. The salts are useful in both their hydrated and non-hydrated forms.An effective amount of pyrophosphate salt useful in the present composition is generally sufficient to provide at least 0.5% by weight of pyrophosphate ions, 0.9–3% by weight. Pyrophosphates also contribute to the preservation of compositions by lowering water activity. Polymers The oral care compositions of the invention also optionally include one or more polymers, such as polyethylene glycols, maleic acid-polyvinyl methyl ether copolymers, polysaccharides (e.g., cellulose derivatives, e.g., carboxymethylcellulose, or polysaccharide gums, e.g., xanthan gum or carrageenan gum). Acidic polymers, e.g., polyacrylate gels, may be provided in the form of their free acids or partially or completely neutralized, water-soluble salts of alkali metals (e.g., potassium and sodium) or ammonium. Certain embodiments include 1:4 to 4:1 copolymers of maleic anhydride or maleic acid with another polymerizable ethylene-unsaturated monomer, e.g., methyl vinyl ether (methoxyethylene) having a molecular weight (MW) of approximately 30,000 to approximately 1,000,000. These copolymers are available, for example, as Gantrez AN 139 (PM 500,000), AN 1 19 (PM250,000) and pharmaceutical grade S-97 (PM 70,000), from GAP Chemical Corporation. Other operational polymers include those such as 1:1 maleic anhydride copolymers with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available, for example, as Monsanto EMA No. 1 103, PM 10,000 and EMA grade 61, and 1:1 acrylic acid copolymers with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone. Generally suitable are olefinicly or ethylenically unsaturated polymerized carboxylic acids containing an olefinic carbon-to-activated carbon double bond and at least one MA / a / 2U22 / Ul10 / 2 carboxyl group, that is, an acid containing an olefinic double bond that readily polymerizes due to its presence in the monomer molecule in either the alpha-beta position relative to the carboxyl group, or as part of a terminal methylene group. Illustrative of such acids are acrylic, methacrylic, ethetacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorosorbic, cinnamic, beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic, 2-benzylacrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric, and maleic acids and anhydrides. Other olefinic monomers that can be copolymerized with such carboxylic monomers include vinyl acetate, vinyl chloride, dimethyl maleate, and similar compounds. The copolymers contain sufficient carboxylic acid groups for water solubility. An additional 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 the polymers are based on unsaturated sulfonic acids selected from acrylamide-alicanesulfonic acids, such as 2-methylpropanesulfonic acid 2-acrylamide having a molecular weight of approximately 1,000 to approximately 2,000,000, as described in United States Patent No. 4,842,847, June 27, 1989, to Zahid, which is incorporated herein by reference. Another useful class of polymeric agents includes polyamine acids, particularly those containing proportions of anionic surface-active amino acids, such as aspartic acid, glutamic acid, and phosphoserine, as described in U.S. Patent No. 4,866,161 to Sikes et al., which is incorporated herein by reference. When preparing oral care compositions, it is sometimes necessary to add a thickening agent to provide a suitable consistency or to stabilize or enhance the formulation's performance. In certain embodiments, thickening agents include carboxyvinyl polymers, carrageenan, 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 tragacanth gum may also be incorporated. Colloidal magnesium aluminum silicate or finely divided silica may be used as a component of the thickening composition to further improve the composition's texture. In certain embodiments, thickening agents are used in an amount of approximately 0.5% to approximately 5.0% by weight of the total composition. Abrasives Natural calcium carbonate is found in rocks such as chalk, limestone, marble, and travertine. It is also the main component of eggshells and mollusk shells. The natural calcium carbonate abrasive of the invention is typically finely divided limestone, which may optionally be refined or partially refined to remove impurities. For use in the present invention, the material has an average particle size of less than 10 microns, for example, 3–7 microns, for example, approximately 5.5 microns. For example, small-particle silica may have an average particle size (D50) of 2.5–4.5 microns. Because natural calcium carbonate can contain a high proportion of relatively large particles if not carefully controlled, which can unacceptably increase abrasiveness, preferably no more than 0.01%, preferably no more than 0.0.04% by weight of the particles would not pass through a 325 mesh. The material has a strong crystalline structure and is therefore much harder and more abrasive than precipitated calcium carbonate. The density of the settled powder for natural calcium carbonate is, for example, between 1 and 1.5 g / cc, for example, approximately 1.2, for example, approximately 1.19 g / cc. There are different polymorphs of natural calcium carbonate, for example, calcite, aragonite, and vaterite; calcite is preferred for the purposes of this invention. An example of a commercially available product suitable for use in the present invention includes GMZ's Vieron® 25-11 FG. Precipitated calcium carbonate is generally prepared by calcining limestone to produce calcium oxide (lime), which can then be converted back into calcium carbonate by reaction with carbon dioxide in water. Precipitated calcium carbonate has a different crystalline structure than naturally occurring calcium carbonate. It is generally more friable and more porous, and therefore has lower abrasiveness and higher water absorption. For use in the present invention, the particles are small, for example, having an average particle size of 1–5 microns, and for example, no more than 0.1%, preferably no more than 0.05% by weight of the particles, which would not pass through a 325 mesh. The particles may have, for example, a D50 of 3–6 microns, for example, 3.8–4.9, for example, approximately 4.3. a D50 of 1-4 mieras, for example, 2.2-2.6 mieras, for example, approximately 2.4 microns, and a D10 of 1-2 microns, for example, 1.2-1.4 microns, for example, approximately 1.3 microns. The particles have a relatively high water absorption, for example, at least 25 g / 100 g, for example, 30-70 g / 100 g. Examples of commercially available products suitable for use in the present invention include, for example, Carbolag® 15 Plus from Lagos Chemical Industry. In certain embodiments, any of the oral care compositions described herein (for example, any of Composition 1.0 and following) may comprise additional abrasives containing calcium, for example, calcium phosphate abrasive, such as tricalcium phosphate (Ca3(PO4)2), hydroxyapatite (CaIO(PO4)e(OH)2), or dicalcium phosphate dihydrate (CaHPO4 · 2H2O, also sometimes referred to herein as DiCal) or calcium pyrophosphate, and / or abrasives of silica, sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite, or other siliceous materials, or combinations thereof. Any silica suitable for oral care compositions, such as precipitating silicas or silica gels, may be used. MA / a / 2U22 / Ul 10 / 2 example, synthetic amorphous silica. Silica may also be available as a thickening agent, for example, particulate silica. For example, silica may also be small-particle silica (for example, Sorbosil AC43 from Ineos Silicas, Warrington, UK). However, additional abrasives are not present, preferably, in a type or quantity that would raise the RDA of the toothpaste to levels that could damage sensitive teeth, for example, greater than 130. Enzymes The oral care compositions described herein (for example, any of Compositions 1.0 and following) may also optionally include one or more enzymes. Useful enzymes include any of the available proteases, glucanohydrolases, endoglycosidases, amylases, mutanases, lipases, and mucinases, or compatible mixtures thereof. In certain embodiments, the enzyme is a protease, dextranase, endoglycosidase, and mutanase. In another embodiment, the enzyme is papain, endoglycosidase, or a mixture of dextranase and mutanase. Additional enzymes suitable for use in the present invention are described in U.S. Patent No. 5,000,939 to Dring et al., U.S. Patent No. 4,992,420, U.S. Patent No. 4,355,022, and U.S. Patent No. 4,154,815. United States Patent No. 4,058,595; United States Patent No. 3,991,177; and United States Patent No.3,696,191, which are incorporated into the present description by reference. An enzyme from a mixture of several compatible enzymes in the present invention constitutes from 0.002% to 2.0% in one embodiment or from 0.05% to 1.5% in another embodiment or even, in another embodiment, from 0.1% to 0.5%. Water Water is present in the oral compositions of the invention. The water used in the preparation of the commercial oral compositions must be deionized and free from organic impurities. Water commonly constitutes the balance of the compositions and, in certain aspects of any of the oral care compositions described herein (e.g., any of Composition 1.0 and subsequent compositions), comprises 5% to 45%, e.g., 10% to 20%, e.g., 25% to 35% by weight of the oral compositions. This amount of water includes free water, which is added, plus the amount introduced with other materials, such as sorbitol or silica, or any component of the invention. The Karl Fischer method is a measure for calculating free water. Moisturizers In certain aspects, the oral care compositions described herein (for example, any of Composition 1.0 and following) comprise a humectant to reduce evaporation and also contribute to preservation by decreasing water activity. Certain humectants may also provide a desirable sweetness or flavor to the compositions. The humectant, based on a pure humectant, generally comprises 15% to 70% in one form or 30% to 65% in another form by weight of the composition. Suitable humectants include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, and propylene glycol, as well as other polyols and mixtures of these humectants. In certain embodiments, mixtures of glycerin and sorbitol may be used as the humectant component of the compositions described herein. The present invention, in its aspect as a method, involves applying a safe and effective amount of the compositions described herein to the oral cavity. The compositions and methods according to the invention are useful in a method for protecting teeth by facilitating repair and remineralization, in particular, for reducing or inhibiting the formation of dental caries, reducing or inhibiting demineralization and promoting remineralization of teeth, reducing tooth hypersensitivity, and reducing, repairing, or inhibiting early enamel lesions, for example, as detected by quantitative light-induced fluorescence (QLF) or electronic caries monitoring (ECM). Quantitative light-induced fluorescence (QLIF) is a visible fluorescent light that can detect early lesions and longitudinally monitor their progression or regression. Normal teeth are fluorescent in visible light; demineralized teeth are not, or only to a lesser degree. The area of ​​demineralization can be quantified, and its evolution monitored. Blue laser light is used to make teeth autofluorescent. Areas that have lost minerals exhibit less fluorescence and appear darker compared to a solid tooth surface. Software is used to quantify the fluorescence of a white spot or the area / volume associated with the lesion. Typically, subjects with existing white spot lesions are recruited as panelists. Measurements are performed in vivo using real teeth. The lesion area / volume is measured at the beginning of the study.The reduction (improvement) in the area / volume of the lesion is measured at the end of 6 months of product use. Data is generally reported as a percentage improvement relative to the baseline value. Electrical caries monitoring is a technique used to measure tooth mineral content based on electrical resistance. Electrical conductance measurement takes advantage of the fact that fluid-filled tubules exposed during enamel demineralization and erosion conduct electricity. As teeth lose minerals, they become less resistant to electrical current due to increased porosity. An increase in the conductance of a patient's teeth, therefore, can indicate demineralization. Studies are typically performed on root surfaces with existing lesions. Measurements are taken in vivo using real teeth. Changes in electrical resistance are measured before and after 6 months of treatment. Additionally, a classic caries score for root surfaces is performed using a tactile probe. Hardness is rated on a three-point scale: hardness, MA / a / 2U22 / Ul10 / 2 tanning or softness. In this type of study, results are typically reported as electrical resistance (higher number is better) for ECM measurements and an improvement in lesion hardness based on the tactile probe score. The methods for determining the desensitizing properties of the compositions described herein use the method described in U.S. Patent No. 5,589,159, which is incorporated herein by reference. This method measures the hydraulic conductance of the materials, providing an objective reduction in fluid flow that correlates with a reduction in fluid flow in the dentinal tubules. In this method, intact, caries-free human molars and restorations are sectioned perpendicular to the long axis of the tooth using a metal saw to form thin sections, or discs, approximately 0.4 to approximately 0.8 mm thick. Sections containing dentin and no enamel were selected for testing and then etched with citric acid solution to remove the staining layer.Each disc was mounted in a device with separate chambers, as described in J. Dent. Research, 57: 187 (1978). This device consists of a special leak-proof chamber connected to a pressurized fluid reservoir containing tissue culture fluid. Using a mixture of pressurized carbon dioxide and nitrogen gas, the fluid can be prepared at a physiological pH. To ensure accuracy, the discs were moistened with artificial saliva (phosphate-buffered saline, PBS) to approximate intraoral conditions. The apparatus includes a glass capillary tube attached to a flow sensor (FLODEC, DeMarco Engineering SA, Geneva). An air bubble is injected into the glass capillary tube. By measuring the bubble's displacement over time, the fluid flow through the dentin disc can be measured. This fluid flow is equivalent to the permeability of the dentin.Therefore, the compositions of the invention are useful in a method for reducing early dental enamel lesions (as measured by QLF or ECM) relative to a composition lacking effective amounts of fluoride and / or arginine. Additionally, the compositions of the invention are useful in methods for reducing harmful bacteria in the oral cavity, for example, methods for reducing or inhibiting gingivitis, reducing the levels of acid-producing bacteria, increasing the relative levels of arginolytic bacteria, inhibiting the formation of microbial biofilm in the oral cavity, raising and / or maintaining the pH of plaque at levels of at least pH 5.5 following the sugar challenge, reducing plaque accumulation and / or cleaning the teeth and oral cavity. Finally, by increasing the pH in the mouth and discouraging pathogenic bacteria, the compositions of the invention are useful for promoting the healing of sores or cuts in the mouth. The compositions and methods according to the invention (for example, Composition 1.0 et seq.) can be incorporated into oral compositions for the care of the mouth and teeth, such as toothpastes, clear pastes, gels, mouthwashes, sprays, and gum. MA / a / ZUZZ / UI lOfZ mascar. As used throughout this description, ranges are used as abbreviations to describe each and every value that falls within the range. Any value within the range may be selected as the endpoint of the range. Additionally, all references cited in this description are hereby incorporated by reference in their entirety. In case of conflict between a definition in this description and that in a cited reference, this description shall prevail. It shall be understood that when formulations are described, they may be described in terms of their ingredients, as is common in the art, even though these ingredients may react with each other in the actual formulation during preparation, storage, and use, and such products are intended to be encompassed by the formulations described. The following examples further describe and demonstrate illustrative embodiments within the scope of the present invention. These examples are provided for illustrative purposes only and should not be construed as limitations of the invention, as many variations are possible without departing from its spirit and scope. Various modifications of the invention, in addition to those shown and described herein, will be obvious to those skilled in the art and are intended to be included in the appended claims. EXAMPLES Example 1 Antibacterial efficacy - Test 1 Saliva-derived biofilms are cultured on a PAH disc at 37°C under 5% CO2. The biofilms are grown on McBain media supplemented with hemin and vitamin K for a total of approximately 60 hours. The media is replaced twice daily (at 12-hour intervals). The resulting biofilm culture is treated once with toothpaste suspensions (see table below) for 2 minutes under agitation (80 rpm). The biofilms are washed twice at 5-minute intervals under agitation (80 rpm). Following treatment, the biofilms are allowed to recover for 3 hours in sterile dH2O at 37°C before harvesting by sonication to dislodge and suspend the bacteria.The collected bacteria are assessed for total biomass using SytoO staining and viability using the Baclight Bacterial Viability Kit (Promega) to quantify the approximate ATP content (expressed as relative luminescence units; RLU) in the biofilms. Bacterial viability is normalized based on Syto9 staining of the biofilm samples. Total zinc content is quantified using ICP-MS. ινΐΛ / a / zuzz / u ι io / z Table 1. Toothpaste Suspensions Toothpaste comprising (% by weight): Guanidinium solution (% by weight) Formula designation 1.0% ZnO, 0.5% ZnCit, and 1.5% Arginine N / A Comparative 1 1.0% ZnO, 0.5% ZnCit N / A Comparative 2 1.0% ZnO, 0.5% ZnCit 0.45% Formula A 1.0% ZnO, 0.5% ZnCit 0.9% Formula B 1.0% ZnO, 0.5% ZnCit 1.8% Formula C Preparation of the suspension: The toothpastes in Table 1 above are resuspended by vortexing in equal volumes of water and guanidinium solution for a final dilution of 1:1:1 toothpaste:water:guanidinium. The wt% in the table above refers to the final wt% relative to the weight of the final toothpaste suspension. The suspensions were evaluated to determine zinc uptake in the biofilm, as well as bacterial ATP, which serves as a measure of viability; lower ATP levels indicate a viable biofilm. Importantly, current data show a trend toward dose-dependent potentiation of zinc delivery when treated with increasing concentrations of guanidinium. The level of zinc delivered to the biofilms in the suspensions with 1.5% arginine and 1.8% guanidine is comparable. The results are shown in Table 2 below. Table 2. Comparative Treatment 1 Comparative Treatment 2 Formula A Formula B Formula C ATP: RLU 947,037 1,211,942 1,169,687 906,827 454,699 StDEV 258,791 253,686 324,958 137,634 93,692 Zinc (ppm) 20.97 15.3 18.27 19.57 21.2 StDEV 2.35 1.22 1.36 2.85 2.01 Similarly, increased zinc delivery is inversely related to bacterial viability, with a dose-dependent reduction in ATP levels as guanidinium concentration increases. However, a notable finding is that there appears to be approximately equivalent zinc delivery and bacterial viability in suspensions containing 1.0% ZnO, 0.5% ZnCit, and 1.5% arginine (Comparative 1) and 1.0% ZnO, 0.5% ZnCit, and 0.9% guanidinium (Formula B). This suggests that similar biofilm destabilization effects can be achieved by using less guanidinium than the amount of arginine used in the Comparative 1 formulation. Furthermore, zinc levels appear to reach maximum delivery after 1.5% in all formulations.Such effectiveness, through the use of less guanidinium, is surprising and represents unexpected potential cost savings without diminishing the antibacterial efficacy of the oral care formulation. Furthermore, while the formulas in Comparative 1 were effective in reducing bacterial viability, the Formula C suspensions (e.g., 1.8% guanidine) showed a significant reduction in bacterial viability compared to the suspensions in Comparative 1 (1.5% arginine). Beyond mere theory, these data suggest that guanidine may be able to enhance the antibacterial efficacy of zinc by promoting improved delivery of the metal to biofilms. Antibacterial efficacy - Test 2 The biofilm cultures are treated with toothpaste suspensions as detailed above in Test 1. Table 3 indicates the compositions of the suspensions being tested: ινΐΛ / a / zuzz / u ι io / z Table 3. Toothpaste Suspensions Toothpaste comprising (% by weight): Guanidinium solution (% by weight) Formula designation 1.0% ZnO, 0.5% ZnCit and 1.5% Arginine N / A Comparative 1 Zinc lactate and 0.454% stannous fluoride N / A Comparative 3 1.0% ZnO, 0.5% ZnCit, 1.5% Formula D The suspensions were evaluated to determine bacterial ATP, which serves as a measure of viability; lower ATP levels indicate that the biofilm is viable. Test 2 formulated suspensions with 1.5% (w / w) guanidinium. Formula D suspensions containing 1.5% guanidinium showed an approximately 26% reduction in bacterial viability compared to the suspensions in Comparative 1 (1.5% arginine). The suspensions in Comparative 3 contained toothpaste with formulations representative of the market. Bacterial viability was compared in Formula D suspensions to those in Comparative 3. The weight percent in the table above refers to the final weight percent relative to the weight of the final toothpaste suspension. The results of the trial are detailed below in Table 4: Table 4. Comparative Treatment 1 Formula D Comparative 3 ATP: RLU 970,915 709,701 639,137 StDEV 290,443 53,523 129,951 MA / a / 2U22 / Ul10 / 2 Antibacterial efficacy - Test 3 The samples are prepared as detailed above in “Test 1”. Table 3 indicates the compositions of the suspensions being tested. In Comparison 4, a commercially available toothpaste formulation is used for the suspension. Table 5. Toothpaste Suspensions Toothpaste comprising (% by weight): Guanidinium solution (% by weight) Formula designation 1.0% ZnO, 0.5% ZnCit, and 1.5% Arginine N / A Comparative 1 Zinc lactate and 0.454% stannous fluoride N / A Comparative 3 Potassium nitrate and sodium fluoride N / A Comparative 4 1.0% ZnO, 0.5% ZnCit 1.5% Formula D The suspensions are evaluated to determine zinc uptake in the biofilm, as well as bacterial ATP, which serves as a measure of viability; lower ATP levels indicate a viable biofilm. Test 3 compares the performance of a toothpaste containing zinc oxide, zinc citrate, and guanidinium. Using a single-treatment static biofilm model, Formula D appears to be more effective in reducing bacterial viability compared to the formula in Comparative 1. In this case, Formula D (e.g., 1.5% guanidinium) resulted in approximately a 17.7% reduction in bacterial viability compared to Comparative 1. Formula D also surpasses the antibacterial efficacy of the formula in Comparative 3 by approximately 32.7%. The wt% in the table above refers to the final wt% relative to the weight of the final toothpaste suspension. The results of the trial are shown in Table 6 below: Comparative Treatment 4 Comparative Treatment 3 Comparative Treatment 1 Formula D ATP: RLU 721,415 445,142 363,986 299,661 SEM 82,433 38,762 54,679 23,558 Zinc (ppm) 0.23 1.93 1.37 2.76 SEM 0.03 0.48 0.18 0.77 Not limited to theory, this improvement in effectiveness can be directly linked to the higher zinc supply for Formula D, which was approximately 2.76 ppm compared to the formula for the Comparative 1 suspension, which was approximately 1.37 ppm, or the Comparative 3 suspension, which was approximately 1.93 ppm. Example 2 Representative toothpaste formulations Description Compound A (% by weight) WATER qs GLYCERIN 35.0 AMORPHOUS SILICA 5.0 GUANIDINE HCL 1.5 ALKALINE PHOSPHATE SALTS 2.35 ANIONIC SURFACTANT 2.0 FLAVOR, COLOR, SWEETENER 2.57 ZINC OXIDE 1.0 NON-IONIC SURFACTANT 0.5 ZINC CITRATE 0.5 SODIUM FLUORIDE 0.32 HUMECTANTS OTHER THAN GLYCERIN 0.4 THICKENER 1.0 ABRASIVE SILICA 10.0 THICKENING SILICA 6.0 PRESERVATIVE 0.4 AMPHOTERIC SURFACTANT 1.25 85% PHOSPHORIC ACID IN SYRUP 0.35 TOTAL COMPONENTS 100.0% Example 3 In a representative formulation, a toothpaste comprises the following: a. 1.0% by weight of zinc oxide b. 0.5% by weight of zinc citrate c. 0.45% by weight or 0.9% by weight % 1.5% or 1.8% by weight of guanidine HCl d. sodium fluoride at approximately 1,450 ppm; and The toothpaste is expected to enhance zinc delivery to biofilms, compared to certain zinc-containing formulations without guanidine, and improve the antibacterial efficacy of zinc. As used throughout this description, intervals are used as shorthand to describe each and every value within the interval. Any value within the interval can be selected as the endpoint of the interval. Additionally, all references cited in this description are incorporated herein by reference in their entirety. In case of conflict between a definition in this description and that in a cited reference, this description shall prevail. Unless otherwise specified, all percentages and quantities expressed in this description and elsewhere in the specification shall be understood to refer to percentages by weight of the total composition. The quantities provided are based on the active weight of the material. While the present invention has been described with reference to the embodiments, those skilled in the art will understand that various modifications and variations of these can be made without departing from the scope of the present invention as defined by the appended claims.

Claims

1. An oral care composition comprising: a. guanidine, in free or salt form; b. zinc oxide and zinc citrate; c. a source of fluoride.

2. The oral care composition according to claim 1, wherein the guanidine is in free form.

3. The oral care composition of any of claims 1-2, wherein the guanidine is partially or completely in salt form.

4. The oral care composition of any of claims 1-3, wherein the guanidine is present in an amount corresponding to 0.3% to 15% by weight of the total weight of the composition.

5. The oral care composition of any of the preceding claims, wherein the guanidine is 0.1% by weight - 5.0% by weight of the total weight of the composition.

6. The oral care composition of any of the preceding claims, wherein guanidine is present at approximately 0.45% by weight of the total weight of the composition.

7. The oral care composition of any of the preceding claims, wherein guanidine is present at approximately 0.9% by weight of the total weight of the composition.

8. The oral care composition of any of the preceding claims, wherein guanidine is present at approximately 1.5% by weight of the total weight of the composition.

9. The oral care composition of any of the preceding claims, wherein guanidine is present at approximately 1.8% by weight of the total weight of the composition.

10. The oral care composition of any of the preceding claims, wherein the guanidine is a salt selected from the group consisting of: guanidine hydrochloride, guanidine monohydrate, guanidine monohydrobromide, guanidine monohydrochloride, guanidine monohydroiodide, guanidine nitrate, guanidine phosphate, guanidine sulfate, and guanidinium chloride.

11. The oral care composition of any of the preceding claims, wherein the guanidine is in the oral care compositions in the form of the guanidinium cation.

12. The oral care composition of any of the preceding claims, wherein the fluoride source is selected from: stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof. MA / a / ZUZZ / UI 10 / Z 13. The oral care composition according to claim 12, wherein the fluoride source is sodium fluoride.

14. The oral care composition of any of the preceding claims, wherein zinc citrate is present in an amount of 0.25 to 0.75% by weight and zinc oxide may be present in an amount of 0.75 to 1.25% by weight based on the weight of the oral care composition.

15. The oral care composition of any of the preceding claims, wherein the zinc citrate is approximately 0.5% by weight.

16. The oral care composition of any of the preceding claims, wherein the zinc oxide is approximately 1.0% by weight.

17. The oral care composition of any of the preceding claims, wherein zinc citrate is approximately 0.5% by weight and zinc oxide is approximately 1.0% by weight.

18. The oral care composition of any of the preceding claims, wherein the oral composition may be any of the following oral compositions selected from the group consisting of: a toothpaste or dentifrice, a mouthwash or mouth rinse, a topical oral gel, and a denture cleaner.

19. The oral care composition of any of the preceding claims, wherein the composition is obtained or can be obtained by combining the ingredients as set forth in any of the preceding compositions.

20. A method for improving oral health comprising applying an effective amount of the oral composition of any of the preceding claims to the oral cavity of a subject in need thereof, wherein the method is effective in: i. reducing or inhibiting the formation of dental caries, ii. reducing, repairing, or inhibiting early enamel lesions, iii. reducing or inhibiting demineralization and promoting remineralization of the teeth, iv. reducing tooth hypersensitivity, v. reducing or inhibiting gingivitis, vi. promoting the healing of sores or cuts in the mouth, vii. reducing the levels of acid-producing bacteria, viii. increasing the relative levels of arginolytic bacteria, ix. inhibiting the formation of microbial biofilm in the oral cavity, x. raising and / or maintaining the pH of the plaque at levels of at least pH 5.5 following the sugar challenge, xii. reducing plaque accumulation.treat dry mouth, MA / a / 2U22 / Ul 10 / 2 xiii. enhance systemic health, including cardiovascular health, xiv. whiten teeth, xv. reduce tooth erosion, xvi. immunize (or protect) teeth against cariogenic bacteria and their effects, and / or xvii. clean teeth and the oral cavity.