Oral care composition and method of use

Abstract

The present invention relates to an oral care composition comprising a first stannous ion source, a second stannous ion source (wherein the second stannous ion comprises stannous pyrophosphate) and a zinc source selected from zinc oxide, zinc citrate, zinc lactate and combinations thereof, and a humectant system comprising glycerol and sorbitol, and a thickening system, and to methods of using and preparing these compositions.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit and priority of U.S. Provisional Application No. 62 / 951,592, filed on December 20, 2019, the entire content of which is incorporated herein by reference. Technical field

[0003] The present invention relates to an oral care composition comprising a first stannous ion source, a second stannous ion source (wherein the second stannous ion comprises stannous pyrophosphate), and a zinc source selected from zinc oxide, zinc citrate, zinc lactate, and combinations thereof, as well as a humectant system comprising glycerol and sorbitol, and a thickening system, and to methods of using and preparing these compositions. Background art

[0004] Oral care compositions face specific challenges in preventing microbial contamination.

[0005] Stannous ions, especially stannous salts such as stannous fluoride, are known antimicrobial agents and are used in various dentifrices as agents for preventing dental plaque. However, the use of stannous salts has some disadvantages, such as instability, a tendency to cause tooth discoloration, astringency, and an unpleasant taste for the user.

[0006] Zinc is also a known antimicrobial agent used in toothpaste compositions. Zinc is a known essential mineral for human health and is reported to help strengthen tooth enamel and promote cell repair. Unfortunately, conventional toothpaste formulations typically require a high concentration of zinc (e.g., 2 wt% or more) to achieve efficacy. At this concentration, zinc imparts a significant astringency to the composition. Therefore, there is a need for improved antibacterial toothpaste formulations that do not have the disadvantages of conventional compositions.

[0007] However, due to the formulation complexity of certain oral care compositions containing both stannous fluoride and one or more zinc sources, these formulations can be a challenge to produce from a manufacturing and supply chain perspective.

[0008] Therefore, in view of the disadvantages and deficiencies of using various antimicrobial agents such as zinc and stannous, there is a need for oral care compositions that have antibacterial efficacy but are also palatable and desirable for the user. Summary of the invention

[0009] Certain oral care compositions containing stannous fluoride and zinc use glycerol as the primary or main humectant. However, it has surprisingly been found that in those compositions containing the same zinc and stannous fluoride, sorbitol can in fact be used as a supplement to or partial replacement for glycerol. The addition of a certain percentage and weight of sorbitol makes the processing of the oral care composition easier, but still allows the oral care formulation to maintain or even improve its therapeutic performance and chemical and physical stability in certain assays. Without being bound by theory, the addition of a determined concentration of sorbitol can allow for a reduction in the heating and mixing times in the processing of certain formulating agents (such as hydroxyethyl cellulose (HEC)).

[0010] In addition, stannous fluoride formulations containing zinc oxide and zinc citrate can provide much-needed antibacterial benefits. However, another unexpected finding is that a stannous fluoride formulation having both sorbitol and glycerol and containing stannous pyrophosphate but only a single zinc source (i.e., zinc oxide) can provide enhanced antibacterial performance relative to a similar formulation containing zinc oxide and zinc citrate.

[0011] For example, in one aspect, the present invention is an oral care composition (Composition 1.0) comprising:

[0012] · a zinc source selected from zinc oxide, zinc citrate, zinc lactate, and combinations thereof (e.g., ZnO and ZnCit, or e.g., ZnO and ZnLac);

[0013] · a first stannous source (e.g., stannous fluoride);

[0014] · a second stannous source, wherein the second stannous source comprises stannous pyrophosphate;

[0015] · a humectant system comprising glycerol and sorbitol, and wherein the amount of sorbitol is 2.5% - 35% of the total weight of the composition (e.g., about 3%, about 3.5%, about 5%, about 7%, about 10%, about 10.5%, about 14%, about 15%, about 20%, about 21%, about 24%, about 25%, about 30% of the total weight of the composition) (e.g., 5% - 35%); and

[0016] · a thickening system comprising a thickening agent selected from carboxyvinyl polymer, carrageenan, hydroxyethyl cellulose, water-soluble salts of cellulose ethers (e.g., sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose), and combinations thereof.

[0017] For example, the present invention encompasses any of the following compositions (values are given as percentages by weight of the total composition unless otherwise indicated):

[0018] 1.1 Composition 1.0, wherein the zinc source comprises zinc oxide.

[0019] 1.2 Composition 1.0, wherein the zinc source comprises zinc oxide and zinc citrate (such as zinc citrate trihydrate).

[0020] 1.3 Any of the foregoing compositions, wherein the ratio of the amount of zinc oxide (e.g., weight %) to the amount of zinc citrate (e.g., weight %) is from 1.5:1 to 4.5:1 (e.g., 2:1, 2.5:1, 3:1, 3.5:1 or 4:1).

[0021] 1.4 Any of the foregoing compositions, which comprises zinc citrate and zinc oxide, wherein zinc citrate is present in an amount of 0.25 to 1.0 wt% (e.g., 0.5 wt%) based on the weight of the oral care composition, and zinc oxide may be present in an amount of 0.75 to 1.25 wt% (e.g., 1.0 wt%).

[0022] 1.5 Any of the foregoing compositions, wherein zinc citrate (such as zinc citrate trihydrate) is about 0.5 wt%.

[0023] 1.6 Any of the foregoing compositions, wherein zinc oxide is about 1.0 wt%.

[0024] 1.7 Any of the foregoing compositions, wherein zinc citrate (such as zinc citrate trihydrate) is about 0.5 wt% and zinc oxide is about 1.0 wt%.

[0025] 1.8 Any of the foregoing compositions, wherein zinc oxide is about 1.0 wt%.

[0026] 1.9 Any of the foregoing compositions, wherein zinc citrate is about 0.8 wt% (e.g., about 0.85 wt%) and zinc oxide is about 1.0 wt%.

[0027] 1.10 Any of the foregoing compositions, wherein the amount of stannous pyrophosphate is 0.1 wt% - 3 wt% of the composition (e.g., about 1 wt% of the composition).

[0028] 1.11 Any of the foregoing compositions, wherein the first stannous ion source is stannous fluoride, other stannous halides such as stannous chloride dihydrate, stannous pyrophosphate, organotin carboxylates such as stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate and stannous citrate, stannous glyoxylate or a mixture thereof.

[0029] 1.12 The composition of 1.11, wherein the first stannous ion source is stannous fluoride (e.g., about 0.45 wt%; e.g., about 0.454 wt%).

[0030] 1.13 Any of the foregoing compositions, which further comprises a fluoride source selected from: stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (e.g., N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof.

[0031] 1.14 Any of the foregoing compositions, wherein the pH value is between 7.5 and 10.5.

[0032] 1.15 Any of the foregoing compositions, which further comprises an effective amount of one or more alkali metal phosphates, such as sodium salts, potassium salts or calcium salts, such as selected from dibasic alkali metal phosphates and pyrophosphate alkali metal salts, such as alkali metal phosphates selected from: disodium hydrogen phosphate, dipotassium hydrogen phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, disodium hydrogen orthophosphate, sodium dihydrogen phosphate, pentapotassium triphosphate, and mixtures of two or more thereof, and the amount thereof is, for example, 1-20% by weight of the composition, such as 2-8%, such as about 5%>.

[0033] 1.16 The alkali metal phosphate of 1.15, wherein the salt comprises tetrapotassium pyrophosphate.

[0034] 1.17 The composition of 1.16, wherein the tetrasodium pyrophosphate is 1-3.0% by weight (e.g., about 2.0% by weight).

[0035] 1.18 The composition of 1.17, wherein the salt comprises sodium tripolyphosphate.

[0036] 1.19 The composition of 1.18, wherein the sodium tripolyphosphate is 0.1-3.0% by weight (e.g., about 2.0% by weight).

[0037] 1.20 Any of the foregoing compositions, which further comprises an abrasive or particles (e.g., silica).

[0038] 1.21 Any of the foregoing compositions, wherein the silica is synthetic amorphous silica (e.g., 1% by weight - 28% by weight) (e.g., 8% by weight - 25% by weight).

[0039] 1.22 Any of the foregoing compositions, wherein the silica abrasive is silica gel or precipitated amorphous silica, such as silica having an average particle size in the range of 2.5 microns to 12 microns.

[0040] 1.23 Any of the foregoing compositions, which further comprises small particle silica having a median particle size (d50) of 1-5 microns (e.g., 3-4 microns) (e.g., about 5 wt% of Sorbosil AC43 obtained from PQ Corporation, Warrington, United Kingdom).

[0041] 1.24 Any of the foregoing compositions, wherein 20-30 wt% of the total silica in the composition is small particle silica (e.g., having a median particle size (d50) of 3-4 microns) and wherein the small particle silica is about 5 wt% of the oral care composition.

[0042] 1.25 Any of the foregoing compositions, which comprises silica, wherein the silica is used as a thickening agent, such as particulate silica.

[0043] 1.26 Any of the foregoing compositions, which further comprises glycerol, wherein the total amount of glycerol is 30-45% (e.g., about 42%).

[0044] 1.27 The composition of 1.30, wherein the amount of glycerol is about 42 wt% of the composition.

[0045] 1.28 Any of the foregoing compositions, wherein the composition comprises an aqueous buffer system, such as wherein the buffer system comprises an organic acid and its alkali metal salts, such as wherein the organic acid is citric acid and the salt is mono-, di- and / or tri-alkali metal citrate, such as mono-, di- and / or tri-lithium, sodium, potassium or cesium citrate, and citric acid).

[0046] 1.29 The composition of 1.28, wherein the buffer system comprises trisodium citrate and citric acid (e.g., 1 to 10 wt% of the composition) (e.g., 2.1 wt% of the composition). For example, the molar ratio of sodium citrate monohydrate, disodium citrate and / or trisodium citrate to citric acid is 1.5 to 5 (e.g., 2 to 4).

[0047] 1.30 The composition of 1.28 or 1.29, wherein the buffer is a citrate buffer comprising sodium citrate (e.g., about 1.5 wt%) and citric acid (e.g., about 0.6 wt%).

[0048] 1.31 Any of the foregoing compositions, which comprises a polymer film.

[0049] 1.32 Any of the foregoing compositions, which comprises a flavoring agent, a fragrance and / or a coloring agent.

[0050] 1.33 Any one of the foregoing compositions, wherein the thickening system comprises hydroxyethyl cellulose (e.g., hydroxyethyl cellulose and carrageenan) (e.g., 0.2% - 0.75% of hydroxyethyl cellulose and carrageenan by total weight %).

[0051] 1.34 Any one of the foregoing compositions, wherein the thickening system comprises sodium carboxymethyl cellulose (e.g., 0.5 wt% - 1.5 wt%)

[0052] 1.35 Any one of the foregoing compositions, which comprises 5% - 40%, such as 10% - 35%, such as about 10%, 15%, 25%, 30% and 35% of water.

[0053] 1.36 According to any one of the foregoing compositions, which comprises other antibacterial agents selected from halogenated diphenyl ethers (e.g., triclosan), herbal extracts and essential oils (e.g., rosemary extract, tea extract, magnolia extract, thymol, menthol, cineole, geraniol, carvacrol, citral, hinokitiol, catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, miswak extract, seabuckthorn extract), biguanide preservatives (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)), phenolic preservatives, hexetidine, octenidine, sanguinarine, povidone iodine, delmopinol, salifluor, metal ions (e.g., zinc salts such as zinc chloride, zinc lactate, zinc sulfate, stannous salts, copper salts, iron salts), sanguinarine, propolis and oxidants (e.g., hydrogen peroxide, buffered sodium peroxyborate or sodium percarbonate), phthalic acid and its salts, monoperoxyphthalic acid and its salts and esters, stearyl ascorbate, oleoyl sarcosinate, alkyl sulfates, dioctyl sulfosuccinate, salicylanilide, domiphen bromide, delmopinol, cinprazide and other piperidyl derivatives, nicin formulations, chlorites; and mixtures of any of the foregoing.

[0054] 1.37 Any one of the foregoing compositions, which includes antioxidants, for example, the antioxidants are selected from coenzyme Q10, PQQ, vitamin C, vitamin E, vitamin A, BHT, anethole - dithione and mixtures thereof.

[0055] 1.38 Any one of the foregoing compositions, which comprises a whitening agent.

[0056] 1.39 Any of the foregoing compositions, which comprises a whitening agent selected from whitening actives, said whitening actives being selected from peroxides, metal chlorites, perborates, percarbonates, peroxyacids, hypochlorites and combinations thereof.

[0057] 1.40 The composition of 1.39, wherein the whitening agent is titanium dioxide.

[0058] 1.41 Any of the foregoing compositions, which further comprises hydrogen peroxide or a hydrogen peroxide source, for example, urea peroxide or a peroxide salt or complex (such as, for example, peroxyphosphate, percarbonate, perborate, peroxosilicate or persulfate; for example calcium peroxyphosphate, sodium perborate, sodium percarbonate, sodium peroxyphosphate and potassium persulfate) or a hydrogen peroxide polymer complex such as a hydrogen peroxide - polyvinylpyrrolidone polymer complex.

[0059] 1.42 Any of the foregoing compositions, which further comprises a polymer, for example an anionic polymer, for example a polycarboxylate polymer (such as a PVM / MA copolymer, in an amount of 0.1 - 5%, for example 0.2 - 2%, for example 0.3 - 1%.

[0060] 1.43 Any of the foregoing compositions, which further comprises microcrystalline cellulose and / or sodium carboxymethylcellulose, for example in an amount of 0.1 - 5%, for example 0.5 - 2%, for example 1%.

[0061] 1.44 Any of the foregoing compositions, which further comprises one or both of the following:

[0062] a. polyethylene glycol in an amount of 1 - 6% (such as 3% by weight); and

[0063] b. propylene glycol in an amount of 1 - 6% (such as 4% by weight).

[0064] 1.45 Any of the foregoing compositions, which further comprises polyvinylpyrrolidone (PVP) in an amount of 0.5 - 3% by weight, such as about 1.25% by weight.

[0065] 1.46 Any of the foregoing compositions, which further comprises an agent that interferes with or prevents bacterial attachment, such as ELA or chitosan.

[0066] 1.47 Any of the foregoing compositions, which comprises glycerol in an amount of 20% - 45% by weight of the composition (such as about 20% by weight, such as about 22% by weight, such as about 25% by weight, such as about 30%, such as about 35%, such as about 40%, such as about 43%)

[0067] Any one of the foregoing compositions, wherein the humectant system comprises glycerol and sorbitol in a weight ratio of 1:0.10 to 0.75:1 (glycerol:sorbitol), where the weight percentages are based on the weight of the humectant system.

[0068] Any one of the foregoing compositions, wherein the amount of sorbitol is 2.5% - 30% of the total weight of the composition (e.g., about 3.5%, about 7%, about 15%, about 17%, about 20%, about 24%, about 24.5%, about 25%, about 30%)

[0069] Any one of Compositions 1.0 - 1.47, wherein the amount of sorbitol is 5% - 35% by weight of the total weight of the composition (e.g., about 5%, about 10%, about 15%, about 17%, about 20%, about 25%, about 30%).

[0070] Any one of the foregoing compositions, wherein the amount of sorbitol is 2.5% - 25% of the total weight of the composition (e.g., about 3%, e.g., about 3.5%, e.g., about 5%, e.g., about 17%, e.g., about 20%, e.g., about 21%, e.g., about 24%, e.g., about 25%).

[0071] Any one of the foregoing compositions, wherein the amount of sorbitol is 5% - 25% of the total weight of the composition.

[0072] Any one of the foregoing compositions, wherein the amount of sorbitol is 20% - 30% of the total weight of the composition.

[0073] Any one of the foregoing compositions, wherein the amount of sorbitol is 25% - 35% of the total weight of the composition.

[0074] Any one of the foregoing compositions, which comprises:

[0075] a. about 1.0% by weight of zinc oxide

[0076] b. about 0.5% by weight of zinc citrate

[0077] c. stannous fluoride (e.g., about 0.45% by weight)

[0078] d. about 1.0% by weight of stannous pyrophosphate

[0079] e. a humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 3.5% of the total weight of the composition; and

[0080] f. a thickening system comprising hydroxyethyl cellulose and carrageenan.

[0081] Any one of 1.56, 1.0 - 1.54, wherein the composition comprises:

[0082] a. About 1.0% by weight of zinc oxide

[0083] b. About 0.5% by weight of zinc citrate

[0084] c. Stannous fluoride (e.g., about 0.45% by weight)

[0085] d. About 1.0% by weight of stannous pyrophosphate

[0086] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 5% of the total weight of the composition; and

[0087] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0088] Any one of 1.57, 1.0 - 1.54, wherein the composition comprises:

[0089] a. About 1.0% by weight of zinc oxide

[0090] b. About 0.5% by weight of zinc citrate

[0091] c. Stannous fluoride (e.g., about 0.45% by weight)

[0092] d. About 1.0% by weight of stannous pyrophosphate

[0093] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 7% of the total weight of the composition; and

[0094] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0095] Any one of 1.58, 1.0 - 1.54, wherein the composition comprises:

[0096] a. About 1.0% by weight of zinc oxide

[0097] b. About 0.5% by weight of zinc citrate

[0098] c. Stannous fluoride (e.g., about 0.45% by weight)

[0099] d. About 1.0% by weight of stannous pyrophosphate

[0100] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 10% of the total weight of the composition; and

[0101] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0102] Any one of 1.59, 1.0 - 1.54, wherein the composition comprises:

[0103] a. About 1.0 wt% zinc oxide

[0104] b. About 0.5 wt% zinc citrate

[0105] c. Stannous fluoride (e.g., about 0.45 wt%)

[0106] d. About 1.0 wt% stannous pyrophosphate and

[0107] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 14% of the total weight of the composition; and

[0108] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0109] Any one of 1.60, 1.0 - 1.54, wherein the composition comprises:

[0110] a. About 1.0 wt% zinc oxide

[0111] b. About 0.5 wt% zinc citrate

[0112] c. Stannous fluoride (e.g., about 0.45 wt%)

[0113] d. About 1.0 wt% stannous pyrophosphate and

[0114] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 15% of the total weight of the composition; and

[0115] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0116] Any one of 1.61, 1.0 - 1.54, wherein the composition comprises:

[0117] a. About 1.0 wt% zinc oxide

[0118] b. About 0.5 wt% zinc citrate

[0119] c. Stannous fluoride (e.g., about 0.45 wt%)

[0120] d. About 1.0 wt% stannous pyrophosphate and

[0121] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 17% of the total weight of the composition; and

[0122] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0123] Any one of 1.62, 1.0 - 1.54, wherein the composition comprises:

[0124] a. About 1.0 wt% zinc oxide

[0125] b. About 0.5 wt% zinc citrate

[0126] c. Stannous fluoride (e.g., about 0.45 wt%)

[0127] d. About 1.0 wt% stannous pyrophosphate and

[0128] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 20% of the total weight of the composition; and

[0129] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0130] Any one of 1.63, 1.0 - 1.54, wherein the composition comprises:

[0131] a. About 1.0 wt% zinc oxide

[0132] b. About 0.5 wt% zinc citrate

[0133] c. Stannous fluoride (e.g., about 0.45 wt%)

[0134] d. About 1.0 wt% stannous pyrophosphate and

[0135] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 21% of the total weight of the composition; and

[0136] [[ID=!]]f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0137] Any one of 1.64, 1.0 - 1.54, wherein the composition comprises:

[0138] a. About 1.0 wt% zinc oxide [[ID=!]]

[0139] b. About 0.5 wt% zinc citrate

[0140] c. Stannous fluoride (e.g., about 0.45 wt%)

[0141] d. About 1.0 wt% stannous pyrophosphate and

[0142] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 24.5% of the total weight of the composition; and

[0143] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0144] Any one of 1.65, 1.0 - 1.54, wherein the composition comprises:

[0145] a. About 1.0 wt% zinc oxide

[0146] b. About 0.5 wt% zinc citrate

[0147] c. Stannous fluoride (e.g., about 0.45 wt%)

[0148] d. About 1.0 wt% stannous pyrophosphate and

[0149] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 25% of the total weight of the composition; and

[0150] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0151] Any one of 1.66, 1.0 - 1.53, wherein the composition comprises:

[0152] a. About 1.0 wt% zinc oxide

[0153] b. About 0.5 wt% zinc citrate

[0154] c. Stannous fluoride (e.g., about 0.45 wt%)

[0155] d. About 1.0 wt% stannous pyrophosphate;

[0156] e. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 30% of the total weight of the composition; and

[0157] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0158] Any one of 1.67, 1.0 - 1.53, wherein the composition comprises:

[0159] a. About 1.0 wt% zinc oxide

[0160] b. About 1.0 wt% stannous pyrophosphate;

[0161] c. Stannous fluoride (e.g., about 0.45 wt%); and

[0162] d. A humectant system comprising glycerol and sorbitol, wherein the amount of sorbitol is about 35% of the total weight of the composition;

[0163] e. Wherein zinc oxide is the sole source of zinc in the composition; and

[0164] f. A thickening system comprising hydroxyethyl cellulose and carrageenan.

[0165] 1.68 Any one of Compositions 1.54 - 1.66, which further comprises a citrate buffer system, wherein the buffer system comprises trisodium citrate and citric acid (for example, the buffer system is about 2.1% by weight of the composition).

[0166] 1.69 Any of the foregoing compositions, when applied to the oral cavity, for example, by rinsing, optionally in combination with brushing, will effectively: (i) reduce or inhibit the formation of dental caries, (ii) reduce, repair or inhibit early 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) relieve tooth hypersensitivity, (v) relieve or inhibit gingivitis, (vi) promote the healing of ulcers or cuts in the mouth, (vii) reduce the level of acid-producing bacteria, (viii) increase the relative level of arginine-decomposing bacteria, (ix) inhibit the formation of microbial biofilms in the oral cavity, (x) after a sugar challenge, raise and / or maintain the pH of dental plaque at a level of at least pH 5.5, (xi) reduce the accumulation of dental plaque, (xii) treat, relieve or alleviate dry mouth, (xiii) clean teeth and the oral cavity, (xiv) reduce corrosion, (xv) prevent dental stains and / or whiten teeth, (xvi) immunize teeth against cariogenic bacteria; and / or (xvii) promote systemic health, including cardiovascular health, for example, by reducing the likelihood of systemic infections occurring through oral tissues.

[0167] 1.70 Any of the foregoing oral compositions, wherein the oral composition can be any one of the oral compositions selected from the following: toothpaste or dentifrice, mouthwash or gargle, topical oral gel, and denture cleanser.

[0168] 1.71 A composition obtained or obtainable by combining the ingredients set forth in any of the foregoing compositions.

[0169] 1.72 Any of the foregoing compositions, wherein zinc oxide and / or zinc citrate is the sole source of zinc.

[0170] 1.73 Any of the foregoing compositions, wherein stannous fluoride and stannous pyrophosphate are the sole sources of stannous.

[0171] 1.74 Any of the foregoing oral compositions, wherein the composition can be dentifrice or mouthwash.

[0172] 1.75 Any of the foregoing oral compositions, wherein the composition can be any one selected from toothpaste, transparent paste, gel, mouthwash, spray, and chewing gum.

[0173] 1.76 Any of the foregoing oral compositions, wherein the composition is incorporated into chewing gum.

[0174] 1.77 A composition obtainable or obtained by combining the ingredients set forth in any of the foregoing compositions.

[0175] 1.78 A composition for use in the uses set forth in any of the foregoing compositions.

[0176] In another embodiment, the present invention encompasses methods of improving oral health, the methods comprising administering to the oral cavity of a subject in need thereof an effective amount of an oral composition of any of the foregoing embodiments, e.g., methods for:

[0177] i. Reducing or inhibiting the formation of dental caries,

[0178] ii. Reducing, repairing or inhibiting early enamel lesions, e.g., as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM),

[0179] iii. Reducing or inhibiting demineralization and promoting remineralization of teeth,

[0180] iv. Alleviating tooth hypersensitivity,

[0181] v. Alleviating or inhibiting gingivitis,

[0182] vi. Promoting the healing of ulcers or cuts in the mouth,

[0183] vii. Reducing the content of acid-producing bacteria,

[0184] viii. Increasing the relative level of arginine-degrading bacteria,

[0185] ix. Inhibiting the formation of microbial biofilms in the oral cavity,

[0186] x. Raising and / or maintaining the pH of dental plaque at a level of at least pH 5.5 after a sugar challenge,

[0187] xi. Reducing dental plaque accumulation,

[0188] xii. Treating xerostomia,

[0189] xiii. Enhancing systemic health, including cardiovascular health, e.g., by reducing the likelihood of systemic infections occurring via oral tissues,

[0190] xiv. Whitening teeth,

[0191] xv. Reducing tooth erosion,

[0192] xvi. Immunizing (or protecting) teeth against cariogenic bacteria and their effects, and / or

[0193] xvii. Cleaning teeth and oral cavity.

[0194] The present invention also includes the use of sodium bicarbonate, sodium methyl cocoyl taurate (tauranol), MIT, benzyl alcohol and combinations thereof in the manufacture of the compositions of the present invention, for example, for use in any of the applicable ranges described in the methods of the above composition 1.0 and the like. Detailed Description

[0195] As used herein, the term "oral composition" refers to the entire composition delivered to the oral surface. The composition is also defined as a product which, during normal use, is not intended for systemic administration of a particular therapeutic agent, is not intended to be swallowed, but is for the purpose of oral activity and remains in the oral cavity for a time sufficient to contact substantially all tooth surfaces and / or oral tissues. Examples of such compositions include, but are not limited to, toothpaste or dentifrice, mouthwash or gargle, topical oral gel, denture cleanser, etc.

[0196] As used herein, unless otherwise specified, the term "dentifrice" refers to a paste, gel or liquid preparation. The dentifrice composition can be in any desired form, such as a deep stripe form, a surface stripe form, a multi-layer form, a form having a gel surrounding the paste, or any combination thereof. Alternatively, the oral composition can be a two-phase dispensed from a compartmental dispenser.

[0197] Stannous ion source

[0198] In some embodiments, the first stannous source comprises a stannous source selected from stannous fluoride, other stannous halides such as stannous chloride dihydrate, stannous pyrophosphate, organic stannous carboxylates such as stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate and stannous citrate, stannous glyoxylate or mixtures thereof. In some embodiments, the first stannous source comprises stannous fluoride.

[0199] Fluoride ion source

[0200] The oral care composition may further comprise one or more fluoride ion sources, such as soluble fluoride salts. A variety of fluoride ion-generating materials can be employed as the source of soluble fluoride in the present composition. Examples of suitable fluoride ion-generating substances are found in U.S. Patent No. 3,535,421 to Briner et al.; U.S. Patent No. 4,885,155 to Parran, Jr. et al. and U.S. Patent No. 3,678,154 to Widder et al., each of which is incorporated herein by reference. Representative fluoride ion sources for use in the present invention (e.g., Composition 1.0 and the like) 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. In cases where the formulation includes a calcium salt, the fluoride salt is a preferred salt in which the fluoride is covalently bound to another atom, e.g., as in sodium monofluorophosphate, rather than merely ionically bound, as in sodium fluoride.

[0201] Surfactant

[0202] In some embodiments, the present invention may include an anionic surfactant, such as compositions of Composition 1.0 and the like, such as water-soluble salts of monoglyceryl monosulfates of higher fatty acids, such as the sodium salt of monosulfated monoglyceryl hydrogenated coconut oil fatty acid, such as sodium N-methyl N-cocoyl taurate, sodium monoglyceride sulfate; higher alkyl sulfates, such as sodium lauryl sulfate; higher alkyl ether sulfates, e.g., a higher alkyl ether sulfate of the formula CH3(CH2) m CH2(OCH2CH2) n OS03X, where m is 6 - 16, e.g., 10, n is 1 - 6, e.g., 2, 3 or 4, and X is Na or, e.g., sodium lauryl polyoxyethylene (2) ether sulfate (CH3(CH2) 10 CH2(OCH2CH2)2OS03Na); higher alkyl aryl sulfonates, such as sodium lauryl benzene sulfonate (sodium lauryl benzene sulfonate); higher alkyl sulfonacetates, such as sodium dodecyl benzene sulfonate (sodium lauryl benzene sulfonate), higher fatty acid esters of 1,2-dihydroxypropane sulfonic acid, sulfocolaurate (N-2-ethyl potassium laurate sulfonacetamide) and sodium lauryl sarcosinate. "Higher alkyl" means, for example, C 6-3o - alkyl. In certain embodiments, the anionic surfactant (when present) is selected from sodium lauryl sulfate and sodium laureth sulfate. When present, the anionic surfactant is present in an effective amount (e.g., greater than 0.001% by weight of the formulation), but not at a concentration that would irritate oral tissues (e.g., 1%), and the optimal concentration depends on the particular formulation and the particular surfactant. In one embodiment, the anionic surfactant is present at 0.03% to 5% by weight (e.g., 1.5%).

[0203] In another embodiment, the cationic surfactants suitable for use in the present invention can be broadly defined as derivatives of aliphatic quaternary ammonium compounds having a long alkyl chain containing 8 to 18 carbon atoms, such as lauryl trimethyl ammonium chloride, cetylpyridinium chloride, cetyl trimethyl ammonium bromide, diisobutylphenoxyethyl dimethylbenzyl ammonium chloride, coconut alkyl trimethyl ammonium nitrite, cetylpyridinium fluoride, and mixtures thereof. Illustrative cationic surfactants are the quaternary ammonium fluorides described in U.S. Patent No. 3,535,421 to Briner et al., which is incorporated herein by reference. Certain cationic surfactants can also act as bactericides in the composition.

[0204] Illustrative non - ionic surfactants that can be used in the compositions of the present invention and the like can be broadly defined as compounds produced by condensing an alkylene oxide group (essentially hydrophilic) with an organic hydrophobic compound that can be essentially aliphatic or alkyl - aromatic. Examples of suitable non - ionic surfactants include, but are not limited to, Pluronics, poly(ethylene oxide) condensates of alkylphenols, condensation products derived from the reaction products of ethylene oxide with 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.

[0205] In another embodiment, exemplary zwitterionic surfactants that can be used in the compositions of the present invention and the like include: betaines (such as cocamidopropyl betaine); derivatives of aliphatic secondary and tertiary amines, where the aliphatic group can be straight - chain or branched, and where 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.

[0206] Surfactants or mixtures of compatible surfactants can be present in the compositions of the present invention at 0.1% to 5% by weight of the total composition, 0.3% to 3% in another embodiment, and 0.5% to 2% in another embodiment.

[0207] Flavoring agent

[0208] The oral care composition of the present invention may also contain a flavoring agent. Flavoring agents useful in the practice of the present invention may include, but are not limited to, essential oils and various flavored aldehydes, esters, alcohols, and the like, 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. Such chemicals as menthol, carvone, and anethole are also suitable. Certain embodiments employ oils of peppermint and spearmint.

[0209] The flavoring agent is incorporated into the oral composition at a concentration of from 0.01% to 1% by weight.

[0210] Chelating agent and anti-calculus agent

[0211] The oral care composition of the present invention may also contain one or more chelating agents capable of complexing calcium present in the bacterial cell wall. This binding of calcium weakens the bacterial cell wall and enhances bacterial lysis.

[0212] Another group of agents suitable for use as chelating agents and anti-calculus agents in the present invention are soluble pyrophosphates. The pyrophosphate used in the compositions of the present invention can be any of the alkali metal pyrophosphates. In certain embodiments, the salt comprises a tetra-alkali metal pyrophosphate, a dihydrogen diphosphate di-alkali metal salt, a monohydrogen tri-alkali metal pyrophosphate, and mixtures thereof, wherein the alkali metal is sodium or potassium. Both hydrated and unhydrated forms of the salt are suitable. The effective amount of pyrophosphate useful in the compositions of the present invention is generally sufficient to provide at least 0.1% by weight of pyrophosphate ions, such as 0.1 to 3% by weight, such as 0.1 to 2% by weight, such as 0.1 to 1% by weight, such as 0.2 to 0.5% by weight. Pyrophosphate also aids in preserving the composition by reducing the activity of water.

[0213] In various embodiments of the present disclosure (e.g., Composition 1.0 and the like), the composition further comprises one or more anti-calculus agents (tartar control agents). Suitable anti-tartar agents include, but are not limited to, monophosphates (e.g., dihydrogen phosphates, hydrogen phosphates, or triphosphates) and P1-6 polyphosphates (e.g., pyrophosphates, tripolyphosphates, tetraphosphates, and hexametaphosphates), zinc salts (e.g., zinc citrate, zinc chloride, zinc citrate trihydrate), Copolymers of (polyvinyl methyl ether (PVM) and maleic acid (MA)), polyaminopropanesulfonic acid (AMPS), polypeptides, polyolefin sulfonates, polyolefin phosphates, and diphosphonates. In certain embodiments, other anti-tartar agents are alkali and / or alkaline earth metal phosphates, such as sodium, potassium, or calcium salts. In certain embodiments, the composition includes monophosphates (e.g., dihydrogen phosphate, hydrogen diphosphate, or triphosphate), P1-6 polyphosphates, Gantrez, or combinations thereof. Still in certain embodiments, the composition includes sodium tripolyphosphate, tetrasodium pyrophosphate, Gantrez, or combinations thereof.

[0214] Polymer

[0215] The oral care compositions of the present invention also optionally contain one or more polymers such as polyethylene glycol, copolymers of polyvinyl methyl ether maleic acid, polysaccharides (e.g., cellulose derivatives such as carboxymethyl cellulose; or polysaccharide gums such as xanthan gum or carrageenan). Acidic polymers (e.g., polyacrylate gels) can 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 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer (e.g., methyl vinyl ether (methoxyethylene)) having a molecular weight (M.W.) of from about 30,000 to about 1,000,000 in a ratio of 1:4 to 4:1. These copolymers are available, for example, as Gantrez AN 139 (M.W. 500,000), AN 119 (M.W. 250,000), and S-97 pharmaceutical grade (M.W. 70,000) from GAF Chemicals Corporation.

[0216] Other functional polymers include those such as 1:1 copolymers of maleic anhydride with ethyl acrylate, 2-hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available, for example, as Monsanto EMA number 1103, M.W. 10,000, and EMA grade 61; and 1:1 copolymers of acrylic acid with methyl methacrylate or 2-hydroxyethyl methacrylate, methyl acrylate or ethyl acrylate, isobutyl vinyl ether, or N-vinyl-2-pyrrolidone.

[0217] Generally speaking, suitable are polymerized olefinic or ethylenically unsaturated carboxylic acids containing activated carbon-carbon double bonds and at least one carboxyl group, i.e., acids containing ethylenic double bonds that are prone to participate in polymerization because they are present in the α-β position relative to the carboxyl group or as part of the terminal methylene group in the monomer molecule. Examples of such acids are acrylic acid, methacrylic acid, ethylacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloxypropionic acid, sorbic acid, α-chlorosorbic acid, cinnamic acid, β-styrylacrylic acid, mucic acid, itaconic acid, citraconic acid, methyl fumaric acid, glutaconic acid, aconitic acid, α-phenylacrylic acid, 2-benzylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbellic acid, fumaric acid, maleic acid, and acid anhydrides. Other different olefin monomers copolymerizable with such carboxylic acid monomers include vinyl acetate, vinyl chloride, dimethyl maleate, etc. The copolymer contains carboxylate groups sufficient for water solubility.

[0218] Another class of polymerizing agents comprises compositions containing homopolymers of substituted acrylamides and / or homopolymers of unsaturated sulfonic acids and their salts, specifically, wherein the polymers are unsaturated sulfonic acids based on those selected from acrylamidoalkylsulfonic acids (such as 2-acrylamido-2-methylpropane sulfonic acid) having a molecular weight of from about 1,000 to about 2,000,000, as described in U.S. Patent No. 4,842,847 to Zahid, issued on June 27, 1989, which is incorporated herein by reference.

[0219] In the preparation of oral care compositions, it is sometimes necessary to add some thickening materials to provide a desired consistency or to stabilize or enhance the performance of the formulation. In certain embodiments, the thickening agents are carboxyvinyl polymers, carrageenan, xanthan gum, 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, gum arabic, and tragacanth gum, can also be incorporated. Colloidal magnesium aluminum silicate or finely divided silica can be used as components of the thickening composition to further improve the texture of the composition. In certain examples, thickening agents are used in an amount of from about 0.5% to about 5.0% by total weight of the composition.

[0220] Abrasive

[0221] Natural calcium carbonate is present in rocks such as chalk, limestone, marble, and travertine. It is also a major component of eggshells and mollusk shells. The natural calcium carbonate abrasive of the present invention is typically ground 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, such as 3 - 7 microns, such as about 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 that are not carefully controlled, which would unacceptably increase abrasiveness, preferably no more than 0.01 wt%, preferably no more than 0.004 wt% of the particles will not pass through a 325 mesh sieve. The material has a strong crystal structure and is thus much harder and more abrasive than precipitated calcium carbonate. The tapped density of natural calcium carbonate is, for example, between 1 and 1.5 g / cc, such as about 1.2, such as about 1.19 g / cc. Natural calcium carbonate exists in different polymorphs, such as calcite, aragonite, and vaterite, and calcite is preferred for the purposes of the present invention. Examples of commercially available products suitable for the present invention include those obtained from GMZ of 25 - 11FG.

[0222] Precipitated calcium carbonate is typically prepared by calcining limestone to produce calcium oxide (lime), which can then be converted back to calcium carbonate by reaction with carbon dioxide in water. Precipitated calcium carbonate has a different crystal structure from natural calcium carbonate. It is generally more friable and porous and thus has lower abrasiveness and higher water absorbency. For use in the present invention, the particles are smaller, such as having an average particle size of 1 - 5 microns, and for example, no more than 0.1 wt%, preferably no more than 0.05 wt% of the particles cannot pass through a 325 mesh sieve. The particles may have, for example, a D50 of 3 - 6 microns, such as 3.8 = 4.9, such as about 4.3; a D50 of 1 - 4 microns, such as 2.2 - 2.6 microns, such as about 2.4 microns; and a D10 of 1 - 2 microns, such as 1.2 - 1.4, such as about 1.3 microns. The particles have a relatively high water absorbency, such as at least 25 g / 100 g, such as 30 - 70 g / 100 g. Examples of commercially available products suitable for the present invention include, for example, those from Lagos Industria Quimica of 15Plus.

[0223] In certain embodiments, the present invention may include additional calcium-containing abrasives, such as calcium phosphate abrasives, such as tricalcium phosphate (Ca3(P04)2), hydroxyapatite (Ca 10(P04)6(OH)2), or dicalcium phosphate dihydrate (CaHPO4·2H2O, sometimes also referred to herein as DiCal), or calcium pyrophosphate; and / or silica abrasive, sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite, or other siliceous materials, or combinations thereof. Any silica suitable for an oral care composition can be used, such as precipitated silica or silica gel. For example, synthetic amorphous silica. Silica can also be used as a thickening agent, such as particulate silica. For example, the silica can also be fine particulate silica (e.g., Sorbosil AC43 from PQ Corporation (Warrington, UK)). However, this additional abrasive is preferably not present in a type or amount that increases the RDA of the dentifrice to a level that could damage sensitive teeth (e.g., greater than 130).

[0224] Water

[0225] Water is present in the oral compositions of the present invention (e.g., composition 1.0 and the like). The water used in the preparation of commercial oral compositions should be deionized and free of organic impurities. Water typically makes up the balance of the composition and accounts for 5 wt% to 45 wt% of the oral composition, such as 10 wt% to 20 wt%, such as 25 - 35 wt%. This amount of water includes the added free water plus the amount of water introduced with other materials such as sorbitol or silica or any component of the present invention. The Karl Fischer method is a measure for calculating free water.

[0226] Humectant

[0227] In certain embodiments of the oral compositions (e.g., composition 1.0 and the like), it is also desirable to incorporate a humectant to reduce evaporation and also to aid in preservation by reducing the activity of water. Certain humectants can also impart a desirable sweetness or flavor to the composition. The humectant typically makes up 15% to 70% by weight of the composition in one embodiment or 30% to 65% in another embodiment, based on the pure humectant.

[0228] Suitable humectants include edible polyhydric alcohols such as glycerol, sorbitol, xylitol, propylene glycol, and other polyols and mixtures of these humectants. A mixture of glycerol and sorbitol can be used in certain embodiments as the humectant component of the compositions herein.

[0229] The present invention, in its method aspect, relates to the application to the oral cavity of a safe and effective amount of the compositions described herein.

[0230] The compositions and methods according to the present invention (Composition 1.0 and the like) can be incorporated into oral compositions for oral and dental care, such as toothpaste, transparent paste, gel, mouthwash, spray, and chewing gum.

[0231] The ranges used throughout are used as shorthand expressions for every value within the range. Any value within the range can be selected as the endpoint of the range. Additionally, all references cited herein are hereby incorporated by reference in their entirety. In the event of a conflict between the definitions in this disclosure and those of the cited references, this disclosure shall control. It should be understood that when describing formulations, they can be described in terms of their ingredients, as is common in the art, although these ingredients may react with each other during preparation, storage, and use in the actual formulation, and such products are intended to be covered by the described formulations.

[0232] The following examples further describe and confirm illustrative embodiments within the scope of the present invention. The examples are given for illustration only and should not be construed as limiting the present invention, as there can be many variations without departing from its spirit and scope. Various modifications to the present invention other than those shown and described herein will be apparent to those skilled in the art and are intended to fall within the scope of the appended claims.

[0233] Example 1

[0234] Table 1.

[0235] Representative toothpaste formulation

[0236]

[0237] Table 1. (continued)

[0238]

[0239] Example 2

[0240] In vitro assay for monitoring metal ion deposition

[0241] Table 2.

[0242]

[0243] Table 2 represents a summary of the stability of stannous fluoride toothpaste (described in Table 1).

[0244] The formulations of the present invention can utilize up to 30% sorbitol to provide processing flexibility, and in some embodiments, can contain only a single zinc source. Due to the contribution of sorbitol and other raw materials with a certain water content, these formulations can contain up to about 18% total water.

[0245] Evaluate the chemical and physical stability of the formulations in Table 1 of Example 1 according to the ICH accelerated aging / stress guidelines and compare them to a positive control formulation (Formulation A) without any sorbitol. Based on the data in Table 2, the formulations B-G in Table 1 are sufficiently stable for fluoride, soluble tin, and soluble zinc and are acceptably buffered to maintain the pH within the target range of 6.5 - 7.5 - see Table 2.

[0246] The purpose of these formulations is to provide a source of soluble and insoluble metals within the toothpaste. Without being bound by theory, the insoluble source can act as a reservoir that remains stable during the shelf life of the toothpaste but becomes available when diluted with saliva during brushing. The stability data in Table 2 demonstrate success in this practice, with total tin and zinc being a substantial percentage compared to the soluble components throughout the accelerated aging of the formulations. Additionally, during the 13-week accelerated aging period, the soluble components showed relatively small changes, indicating successful metal stability and suggesting that compositions with a certain amount of sorbitol function comparably to those with only glycerol.

[0247] Example 3

[0248] The University of Manchester anaerobic model provides a more sensitive indication of the potential efficacy of the formulations described herein. In this model, saliva collected from 4 healthy volunteers was pooled and used as an inoculum. Each sample was processed in triplicate, twice daily, for 8 days. Biofilms were recovered after 16 treatments to measure ATP (RLU) as the endpoint of viable bacteria. Toothpastes showing lower ATP scores provide more effective antibacterial performance. A market-based toothpaste formulation containing NaF and KNO3 active substances was used as the "negative control" as indicated in the table below.

[0249] In this study, two independent tests were conducted with the toothpaste prototypes of the present invention. The formulations referred to here are the same as those described in Table 1 of Example 1 above. [[ID=,14]]

[0250] In the first trial, it was surprisingly found that both Formulation B (containing 5% sorbitol, zinc citrate, and zinc oxide) and Formulation G (containing 30% sorbitol, ZnO only) were statistically significantly superior to the Formulation A standard without sorbitol. It can be seen that Formulation G (30% sorbitol, single ZnO) provided excellent performance superior to all other samples.

[0251] Table 3. Viable bacteria as ATP (RLU) - Manchester model, Trial 1

[0252]

[0253] * indicates no common letter = Sign. Diff @ 95% CI, Tukey method, N = 26 per cell

[0254] **The negative control was a commercially available formulation containing NaF and KNO3 as active ingredients.

[0255] In additional studies, Formulation A standard (positive control) and Formulation G were included and compared with Formulation C (10% sorbitol, zinc oxide, and zinc citrate). Formulation G, containing 30% sorbitol and zinc oxide (where zinc oxide was the sole zinc source), performed very well and was comparable to the positive control (formulation) with two zinc sources: zinc oxide and zinc citrate. In controlling anaerobic biofilms, all tested stannous fluoride preparations (Preparations A - G) performed significantly better than the negative control.

[0256] Table 4. Viable bacteria as ATP (RLU) - Manchester model, Experiment 2

[0257]

[0258] *Indicates no common letters = Sign. Diff @ 95% CI, Tukey method, N = 26 per cell

[0259] **The negative control was a commercially available formulation containing NaF and KNO3 as active ingredients.

[0260] Plaque glycolysis model: The formulations referred to here are the same as those described in Table 1 above.

[0261] An in vitro adaptation of the glycolysis model described by White et al., Journal of Clinical Dentistry, #6 Special Issue, p 69 - 78, (1995), was used to indirectly measure biofilm health, the content of which is incorporated herein by reference. Briefly, the method quantifies the glycolytic effect of toothpaste formulations on in vitro biofilm pools of treated anaerobic and aerobic bacteria. The efficacy of each toothpaste formulation is based on the change in biofilm pH. A lower average pH change indicates a reduction in viable bacteria and greater antibacterial properties of the corresponding test toothpaste. Finally, in these studies, untreated cells were used as the negative control.

[0262] There were two plaque glycolysis tests conducted with the toothpaste prototypes of the present invention. In the first test, Formulation A (positive control) was compared with Formulation E (20% sorbitol, zinc citrate, and zinc oxide). Surprisingly, it was found that the Formulation E prototype was statically superior to the standard.

[0263] Table 5. Plaque glycolysis study - average pH change at treatment, Experiment 1

[0264]

[0265] *Indicates no common letters = Sign. Diff @ 95% CI, Tukey method, N = 3 per cell

[0266] **Negative control, untreated biofilm

[0267] The second plaque glycolysis study compared Formulation C (10% sorbitol, zinc citrate, and zinc oxide) and Formulation F (30% sorbitol, zinc oxide, and zinc citrate) with a positive control (Formulation A) and a negative control (untreated biofilm). The 10% sorbitol formulation of Formula C was comparable to the sorbitol-free standard (Formula A). The 30% sorbitol formulation (i.e., Formula F) showed significantly better performance than the positive control standard of Formula A.

[0268] Table 6. Plaque Glycolysis Study - Mean pH Change during Treatment, Experiment 2

[0269]

[0270] *Indicates no common letters = Sign. Diff @ 95% CI, Tukey method, N = 3 per cell

[0271] **Negative control, untreated biofilm

[0272] Example 4

[0273] The addition of sorbitol surprisingly contributes to the manufacture of the oral care compositions of the present invention.

[0274] In one aspect, the addition of sorbitol allows for a reduction in the temperature of certain steps of the preparation process and a reduction in the time spent hydrating and mixing gums present in the formulation such as HEC and carrageenan. In one aspect, the addition of sorbitol enables a reduction in temperature and time to heat and hydrate the gums from 80 degrees Celsius (without sorbitol) to 50 degrees Celsius (with sorbitol).

[0275] Furthermore, Tables 7 and 8 (below) also show that the physical stability (e.g., equivalent functionality) of certain formulations containing 10% sorbitol and / or exhibit a slight improvement compared to formulations without sorbitol. The formulations referred to in Tables 7 and 8 are the same as those detailed in Table 1 above (Example 1). Thus, the addition of sorbitol in certain formulations can contribute to production efficiency while maintaining the physical stability of sorbitol-free formulations:

[0276] Table 7.

[0277]

[0278] Table 8.

[0279]

[0280] The ranges used throughout are used as a shorthand expression for each value within the range. Any value within the range can be selected as an endpoint of the range. In addition, all references cited herein are incorporated by reference in their entirety. In the event of a conflict between the definitions in the present disclosure and those of the cited references, the present disclosure prevails.

[0281] Unless otherwise indicated, all percentages and amounts expressed herein and elsewhere in this specification are to be understood as being weight percentages. The given amounts are based on the effective weight of the materials.

[0282] Although the invention has been described with reference to embodiments, those skilled in the art will appreciate that various modifications and variations can be made therein without departing from the scope of the invention as defined by the appended claims.

Claims

1. An oral care composition, the oral care composition comprising: a. A zinc source comprising zinc oxide and zinc citrate; b. A first stannous source; c. A second stannous source, wherein the second stannous source comprises stannous pyrophosphate; d. A humectant system comprising glycerin and sorbitol, and wherein the sorbitol is present in an amount of 17% to 35% by weight; and e. A thickening system comprising a thickening agent selected from carrageenan, hydroxyethyl cellulose, and combinations thereof, wherein all weight percentages are based on the total weight of the oral care composition.

2. The oral care composition according to claim 1, wherein the ratio of the amount of zinc oxide to the amount of zinc citrate is from 1.5:1 to 4.5:

1.

3. The oral care composition according to any one of the preceding claims, comprising zinc citrate and zinc oxide, wherein the zinc citrate is present in an amount of 0.25 to 1.0% by weight, and the zinc oxide is present in an amount of 0.75 to 1.25% by weight.

4. The oral care composition according to claim 1 or 2, wherein the first stannous source is selected from stannous fluoride; stannous chloride dihydrate; stannous pyrophosphate; organic stannous carboxylates, the organic stannous carboxylates being stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate, or stannous citrate; stannous glyoxylate; or mixtures thereof.

5. The oral care composition according to claim 1 or 2, wherein the first stannous source is stannous fluoride.

6. The oral care composition according to claim 1 or 2, wherein the composition comprises one or more alkali metal phosphates selected from disodium hydrogen phosphate, dipotassium hydrogen phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, monosodium phosphate, pentapotassium triphosphate, and mixtures thereof.

7. The oral care composition according to claim 6, wherein the composition comprises the alkali metal phosphate in an amount of 1% to 20% by weight.

8. The oral care composition according to claim 1 or 2, wherein the humectant system comprises glycerin and sorbitol in a weight percentage ratio of 1:0.1 to 0.75:1 (glycerin:sorbitol).

9. The oral care composition according to claim 5, wherein the composition comprises: zinc oxide present in an amount of about 1% by weight, zinc citrate present in an amount of about 0.5% by weight, stannous fluoride present in an amount of about 0.45% by weight, and stannous pyrophosphate present in an amount of about 1% by weight.

10. The oral care composition according to claim 5, wherein the composition comprises: zinc oxide present in an amount of about 1% by weight, zinc citrate present in an amount of about 0.5% by weight, stannous fluoride present in an amount of about 0.45% by weight, stannous pyrophosphate present in an amount of about 1.0% by weight, and a thickening system comprising hydroxyethyl cellulose and carrageenan.

11. The oral care composition according to claim 5, wherein the composition comprises: zinc oxide present in an amount of about 1.0% by weight, stannous pyrophosphate present in an amount of about 1.0% by weight, and Stannous fluoride present in an amount of about 0.45% by weight.

12. The oral care composition according to claim 9, further comprising a citrate buffer system, wherein the buffer system comprises trisodium citrate and citric acid.

13. The oral care composition according to claim 1 or 2, wherein the composition is any one selected from toothpaste, clear paste, gel, mouthwash, spray and chewing gum.

14. Use of an oral care composition according to claim 1 in the preparation of a medicament for controlling anaerobic biofilms, which is achieved by administering an effective amount of the oral care composition, wherein the oral care composition is administered to the oral cavity of a subject in need thereof.

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