Oral care compositions and methods of use

Abstract

The present invention relates to oral care compositions comprising zinc phosphate, a first stannous source (such as stannous fluoride) and a second stannous source, wherein the second stannous source comprises stannous pyrophosphate, and to methods of using and preparing these compositions. The present invention allows for the provision of oral care compositions having antibacterial efficacy but which are also palatable and desirable to the user.

Description

[0001] This application is a divisional application of a Chinese patent application with an application date of December 20, 2017, an application number of "201780079006.4", and an invention title of "Oral Care Compositions and Methods of Use".

[0002] Cross-reference to Related Patent Applications

[0003] This application claims priority to U.S. Provisional Application No. 62 / 437,091, filed on December 21, 2016, the contents of which are hereby incorporated by reference in their entirety. Technical Field

[0004] The present invention relates to oral care compositions comprising zinc phosphate, a first stannous ion source, and a second stannous ion source, wherein the second stannous ion comprises stannous pyrophosphate, and to methods of using and preparing these compositions. Background Art

[0005] Oral care compositions face particular challenges in preventing microbial contamination.

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

[0007] Stannous ions, particularly stannous salts such as stannous fluoride, are also known as antimicrobial agents and are used as agents for preventing dental plaque in a variety of dentifrices. However, there are some drawbacks to using stannous salts, such as instability, a tendency to cause tooth discoloration, astringency, and an unpleasant taste for the user.

[0008] Although zinc phosphate (Zn3(PO4)2) is soluble in acidic or basic solutions, such as solutions of inorganic acids, acetic acid, ammonia, or alkali metal hydroxides, it is insoluble in water. See, for example, Merck Index, 13th Edition, (2001) page 1812, monograph number 10205. In part because zinc phosphate is a material that would be considered generally inert in the art, it is commonly used in dental cements, such as for the cementation of inlays, crowns, bridges, and orthodontic appliances, which are intended to last for many years in the mouth. Dental zinc phosphate cements are typically prepared by mixing zinc oxide and magnesium oxide powders with a liquid consisting primarily of phosphoric acid, water, and a buffer, and thus the cement containing zinc phosphate is formed in situ by reaction with phosphoric acid.

[0009] Oral care compositions containing a stannous ion source have demonstrated excellent clinical benefits, particularly in reducing gingivitis and treating or preventing erosive tooth demineralization. Stannous fluoride is well known in clinical dentistry for its more than four decades of therapeutic benefits. However, until recently, its popularity has been limited by its instability in aqueous solution. The instability of stannous fluoride in water is primarily due to the presence of stannous ions (Sn 2+ Stannous salts are susceptible to hydrolysis at pH values ​​above 4, resulting in precipitation from solution with the consequent loss of therapeutic properties.

[0010] One approach to overcoming the stannous ion stability problem is to limit the amount of water in the composition to very low levels, or to use a dual phase system. Both of these solutions to the stannous ion problem have disadvantages. Low moisture oral care compositions can be difficult to formulate with the desired rheological properties, and dual phase compositions are significantly more expensive to manufacture and package.

[0011]

[0006] Therefore, in view of the drawbacks and deficiencies of using various antimicrobial agents such as zinc and stannous, there exists a need for oral care compositions that have antimicrobial efficacy but are also palatable and desirable to the user. Summary of the invention

[0012] The zinc source comprising zinc phosphate in a selected concentration and amount increases or improves the delivery of stannous in the oral cavity of the user. The present invention improves the delivery or availability of Sn, wherein the improvement is relative to comparable products currently on the market.

[0013] In one aspect, the present invention is an oral care composition (Composition 1.0) comprising:

[0014] a zinc source comprising zinc phosphate;

[0015] a first stannous source (e.g., stannous fluoride); and

[0016] - A second stannous source, wherein the second stannous source comprises stannous pyrophosphate.

[0017] For example, the present invention contemplates any of the following compositions (unless otherwise indicated, values ​​are given as a percentage of the total weight of the composition):

[0018] 1.1 Composition 1, wherein the zinc phosphate is a preformed salt of zinc phosphate (eg, zinc phosphate hydrate).

[0019] 1.2 Any of the foregoing compositions, wherein the amount of zinc phosphate is from 0.05% to 10% by weight, such as from 0.1% to 8% by weight, or from 0.5% to 5% by weight, or from 0.5% to 4% by weight, or from 1% to 4% by weight, or from 1% to 3% by weight, or from 2% to 3% by weight, or about 1% by weight, or about 2% by weight, or about 2.25% by weight, or about 2.5% by weight, relative to the weight of the oral care composition.

[0020] 1.3 Any of the foregoing compositions, wherein the amount of stannous pyrophosphate is from 0.1% to 3% by weight of the composition (e.g., about 1% by weight of the composition).

[0021] 1.4 Any of the foregoing compositions, wherein the amount of stannous pyrophosphate is about 0.2% by weight.

[0022] 1.5 Any of Compositions 1.1–1.4, wherein the amount of stannous pyrophosphate is about 0.3% by weight.

[0023] 1.6 Any of Compositions 1.1–1.4, wherein the amount of stannous pyrophosphate is about 0.5% by weight.

[0024] 1.7 Any of Compositions 1.1–1.4, wherein the amount of stannous pyrophosphate is about 0.75% by weight.

[0025] 1.8 Any of Compositions 1.1–1.4, wherein the amount of stannous pyrophosphate is about 1.0% by weight.

[0026] 1.9 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 mixtures thereof.

[0027] 1.10 The composition of 1.14, wherein the first stannous ion source is stannous fluoride (e.g., about 0.45% by weight; e.g., about 0.454% by weight).

[0028] 1.11 Any of the foregoing compositions, further comprising a fluoride source selected from: stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, fluorinated amines (e.g., N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof.

[0029] 1.12 Any of the foregoing compositions, wherein the pH is between 7.5 and 10.5.

[0030] 1.13 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 alkali metal pyrophosphates, such as alkali metal phosphates selected from the following: 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, the amount thereof being, by weight of the composition, for example 1-20%, for example 2-8%, for example about 5%.

[0031] 1.14 The alkali metal phosphate of 1.13, wherein the salt comprises tetrapotassium pyrophosphate.

[0032] 1.15 The composition of 1.14, wherein the tetrasodium pyrophosphate is 0.1–3.0% by weight (for example about 2.0% by weight).

[0033] 1.16 The composition of 1.13, wherein the salt comprises sodium tripolyphosphate.

[0034] 1.17 The composition of 1.16, wherein the sodium tripolyphosphate is 0.1–3.0% by weight (for example about 2.0% by weight).

[0035] 1.18 Any of the foregoing compositions, which further comprises an abrasive or particulate (e.g., silica).

[0036] 1.19 Any of the foregoing compositions, wherein the silica is synthetic amorphous silica (e.g., 1 wt% - 28 wt%) (e.g., 8 wt% - 25 wt%).

[0037] 1.20 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 to 12 microns.

[0038] 1.21 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).

[0039] 1.22 Any of the foregoing compositions, wherein 20-30% by weight 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% by weight of the oral care composition.

[0040] 1.23 Any of the foregoing compositions, which comprises silica, wherein the silica is used as a thickener, such as particulate silica.

[0041] Any one of the aforementioned compositions further comprises glycerol, wherein the total amount of glycerol is 2.0 - 5.0% (e.g., about 4%).

[0042] The composition of 1.25, wherein the amount of glycerol is about 4% by weight of the composition.

[0043] Any one of the aforementioned compositions, wherein the composition comprises an aqueous buffer system, for example, wherein the buffer system comprises an organic acid and its alkali metal salts, for example, wherein the organic acid is citric acid and the salt is mono-, di- and / or tri-alkali metal citrate, for example, mono-, di- and / or trilithium, sodium, potassium or cesium citrate, and citric acid).

[0044] The composition of 1.27, wherein the buffer system comprises trisodium citrate and citric acid (e.g., 1 to 10% by weight of the composition) (e.g., 1.2% by weight 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).

[0045] The composition of 1.28, wherein the buffer is a citrate buffer comprising sodium citrate (e.g., about 1.0% by weight) and citric acid (e.g., about 0.2% by weight).

[0046] Any one of the aforementioned compositions, which comprises a polymer film.

[0047] Any of the aforementioned compositions, which comprises a flavoring agent, an aromatic agent and / or a coloring agent.

[0048] Any one of the aforementioned compositions, wherein the composition comprises a thickening agent selected from: carboxyvinyl polymer, carrageenan, hydroxyethyl cellulose and water-soluble salts of cellulose ethers (e.g., sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose).

[0049] Any one of the aforementioned compositions, wherein the composition comprises sodium carboxymethyl cellulose (e.g., 0.5% - 1.5% by weight)

[0050] Any one of the aforementioned compositions, which comprises 5% - 40%, for example 10% - 35%, for example about 10%, 15%, 25%, 30% and 35% of water.

[0051] 1.34 According to any one of the foregoing compositions, which comprises other antibacterial agents selected from halogenated diphenyl ethers (such as triclosan), herbal extracts and essential oils (such as 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 (such as chlorhexidine, alexidine or octenidine), quaternary ammonium compounds (such as 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 (such as zinc salts such as zinc chloride, zinc lactate, zinc sulfate, stannous salts, copper salts, iron salts), sanguinarine, propolis and oxidizing agents (such as hydrogen peroxide, buffered sodium perborate or sodium percarbonate), phthalic acid and its salts, monoperoxyphthalic acid and its salts and esters, stearyl ascorbate, oleoyl sarcosine, alkyl sulfates, dioctyl sulfosuccinate, salicylanilide, domiphen bromide, delmopinol, cinprazide and other piperidyl derivatives, nicin formulations, chlorites; and mixtures of any of the foregoing.

[0052] 1.35 Any of the foregoing compositions, which comprises an antioxidant selected from, for example, coenzyme Q-10, PQQ, vitamin C, vitamin E, vitamin A, BHT, anethole dithiolthione, and mixtures thereof.

[0053] 1.36 Any of the foregoing compositions, which comprises a brightening agent.

[0054] 1.37 According to any one of the foregoing compositions, which comprises a brightening agent selected from brightening active agents, the brightening active agents being selected from peroxides, metal chlorites, perborates, percarbonates, peroxyacids, hypochlorites and combinations thereof.

[0055] 1.38 The composition of 1.36, wherein the brightening agent is titanium dioxide.

[0056] 1.39 Any of the foregoing compositions further comprises hydrogen peroxide or a hydrogen peroxide source, such as carbamide peroxide or a peroxide salt or complex (e.g., such as peroxophosphate, percarbonate, perborate, peroxosilicate or persulfate; e.g., calcium peroxophosphate, sodium perborate, sodium percarbonate, sodium peroxophosphate and potassium persulfate) or a hydrogen peroxide polymer complex such as a hydrogen peroxide-polyvinylpyrrolidone polymer complex.

[0057] 1.40 Any of the foregoing compositions further comprises an anionic surfactant, such as sodium lauryl sulfate.

[0058] 1.41 Any of the foregoing compositions further comprises microcrystalline cellulose and / or sodium carboxymethylcellulose, for example, in an amount of 0.1 - 5%, such as 0.5 - 2%, such as 1%.

[0059] 1.42 Any of the foregoing compositions further comprises polyethylene glycol in an amount of 1 - 6% (e.g., 2% by weight).

[0060] 1.43 Any of the foregoing compositions further comprises an agent that interferes with or prevents bacterial attachment, such as ELA or chitosan.

[0061] 1.44 Any of the foregoing compositions comprises:

[0062] about 1.0% by weight of zinc phosphate

[0063] about 0.2% by weight of stannous pyrophosphate

[0064] about 2.0% by weight of sodium pyrophosphate

[0065] 1.45 Any of the foregoing compositions comprises:

[0066] about 1.0% by weight of zinc phosphate

[0067] about 0.3% by weight of stannous pyrophosphate

[0068] about 2.0% by weight of sodium pyrophosphate

[0069] 1.46 Any of 1.0–1.43, wherein the composition comprises

[0070] about 1.7% by weight of zinc phosphate

[0071] about 1.0% by weight of stannous pyrophosphate

[0072] about 2.0% by weight of sodium pyrophosphate

[0073] 1.47 Any of the compositions 1.44–1.46 further comprises a citrate buffer system, wherein the buffer system comprises trisodium citrate and citric acid (e.g., the buffer system is about 1.2% by weight of the composition).

[0074] 1.48 Any of the foregoing compositions, when applied to the oral cavity, for example by rinsing, optionally in combination with brushing, will be effective in: (i) reducing or inhibiting the formation of dental caries, (ii) reducing, repairing or inhibiting early enamel lesions, e.g., as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM), (iii) reducing or inhibiting demineralization and promoting remineralization of teeth, (iv) alleviating tooth hypersensitivity, (v) alleviating or inhibiting gingivitis, (vi) promoting the healing of ulcers or cuts in the mouth, (vii) reducing the level of acidogenic bacteria, (viii) increasing the relative level of arginine-degrading bacteria, (ix) inhibiting the formation of microbial biofilms in the oral cavity, (x) raising and / or maintaining the pH of dental plaque at a level of at least pH 5.5 after a sugar challenge, (xi) reducing the accumulation of dental plaque, (xii) treating, alleviating or reducing dry mouth, (xiii) cleaning teeth and the oral cavity, (xiv) reducing erosion, (xv) preventing dental stains and / or whitening teeth, (xvi) immunizing teeth against cariogenic bacteria; and / or (xvii) promoting systemic health, including cardiovascular health, e.g., by reducing the likelihood of systemic infections occurring through oral tissues.

[0075] 1.49 Any of the foregoing oral compositions, wherein the oral composition can be any of the oral compositions selected from: toothpaste or dentifrice, mouthwash or rinse, topical oral gel, and denture cleanser.

[0076] 1.50 A composition obtained or obtainable by combining the ingredients set forth in any of the foregoing compositions.

[0077] 1.51 Any of the foregoing compositions, wherein zinc phosphate is the sole source of zinc.

[0078] 1.52 Any of the foregoing compositions, wherein stannous fluoride and stannous pyrophosphate are the sole sources of stannous.

[0079] 1.53 Any of the foregoing compositions, wherein the humectant is selected from: edible polyols (e.g., glycerol, sorbitol, xylitol, propylene glycol), polyhydric alcohols, and mixtures thereof.

[0080] 1.54 Any of the foregoing compositions, wherein the humectant is sorbitol (e.g., about 40 wt%, about 41% or about 42 wt%).

[0081] 1.55 A composition obtained or obtainable by combining the ingredients set forth in any of the foregoing compositions.

[0082] 1.56 A composition for use as set forth in any of the foregoing compositions.

[0083] In another embodiment, the present invention encompasses methods for improving oral health, the methods comprising applying to the oral cavity of a subject in need thereof an effective amount of an oral composition of any of the above embodiments, e.g., methods for:

[0084] i. reducing or inhibiting the formation of dental caries,

[0085] ii. reducing, repairing or inhibiting early enamel lesions, e.g., as detected by quantitative light-induced fluorescence (QLF) or electrical caries monitor (ECM),

[0086] iii. alleviating or inhibiting tooth demineralization and promoting tooth remineralization,

[0087] iv. alleviating tooth hypersensitivity,

[0088] v. alleviating or inhibiting gingivitis,

[0089] vi. promoting the healing of ulcers or cuts in the mouth,

[0090] vii. reducing the level of acidogenic bacteria,

[0091] viii. increasing the relative level of arginine-degrading bacteria,

[0092] ix. inhibiting the formation of microbial biofilms in the oral cavity,

[0093] x. raising and / or maintaining the pH of dental plaque at a level of at least pH 5.5 after a sugar challenge,

[0094] xi. reducing the accumulation of dental plaque,

[0095] xii. treating dry mouth,

[0096] xiii. enhancing overall health, including cardiovascular health, e.g., by reducing the likelihood of systemic infections occurring via oral tissues,

[0097] xiv. whitening teeth,

[0098] xv. reducing tooth erosion,

[0099] xvi. immunizing (or protecting) teeth against cariogenic bacteria and their action, and / or

[0100] xvii. cleaning teeth and the oral cavity.

[0101] The present invention also includes the use of sodium bicarbonate, sodium methyl cocoyl taurate (tauranol), MIT and benzyl alcohol and combinations thereof in the manufacture of the compositions of the present invention, e.g., for any of the applicable uses described in the methods of the above composition 1.0 and the like. Detailed embodiments

[0102] 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 for systemic administration of a specific therapeutic agent, is not intended to be swallowed, but for the purpose of oral activity, 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.

[0103] 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 separate chamber dispenser.

[0104] Stannous ion source

[0105] 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, organotin 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.

[0106] Fluoride ion source

[0107] The oral care composition may further comprise one or more fluoride ion sources, such as soluble fluoride salts. A variety of fluoride ion-generating substances can be used as the source of soluble fluoride in the compositions of the present invention. 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 No. 3,678,154, each of these patents being 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 contains a calcium salt, the fluoride salt is the preferred salt, where the fluoride is covalently bound to another atom, e.g., as in sodium monofluorophosphate, rather than merely ionically bound, as in sodium fluoride.

[0108] Surfactant

[0109] The present invention may include an anionic surfactant in some embodiments, such as Composition 1.0 and compositions such as, for example, water-soluble salts of monoglyceryl monosulfates of higher fatty acids, such as sodium salt of monosulfated monoglyceryl hydrogenated coconut oil fatty acid, such as sodium N-methyl-N-cocoyl taurate, sodium lauryl monoglycerosulfate; higher alkyl sulfates, such as sodium lauryl sulfate; higher alkyl ether sulfates, for example, higher alkyl ether sulfates of the formula CH3(CH2) m CH2(OCH2CH2) n OS03X, where m is 6 - 16, such as 10, n is 1 - 6, such as 2, 3 or 4, and X is Na or, for example, sodium lauryl polyoxyethylene(2) ether sulfate (CH3(CH2) 10 CH2(OCH2CH2)2OS03Na); higher alkyl aryl sulfonates, such as sodium lauryl benzene sulfonate (sodium dodecylbenzenesulfonate); higher alkyl sulfonacetates, such as sodium dodecylbenzenesulfonate (sodium dodecylbenzenesulfonate), higher fatty acid esters of 1,2-dihydroxypropane sulfonic acid, sulfolaurates (potassium N-2-ethyllaurylsulfonylacetamide) and sodium lauryl sarcosinate. "Higher alkyl" means, for example, C 6-3 o alkyl. In certain embodiments, the anionic surfactant (when present) is selected from sodium lauryl sulfate and sodium lauryl ether 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% by weight).

[0110] In another embodiment, cationic surfactants suitable for 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 by reference. Certain cationic surfactants can also act as bactericides in the composition.

[0111] Compositions 1.0 and the following illustrative nonionic surfactants that can be used in the compositions of the present invention can be broadly defined as compounds produced by condensing alkylene oxide groups (essentially hydrophilic) with organic hydrophobic compounds that can be essentially aliphatic or alkyl aromatic compounds. Examples of suitable nonionic 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 substances.

[0112] Exemplary amphoteric surfactants that can be used in Compositions 1.0 and the following in the compositions of the present invention include: betaines (such as cocoamidopropyl betaine); derivatives of aliphatic secondary and tertiary amines, where the aliphatic group can be straight-chain or branched-chain, and where one of the aliphatic substituents contains from about 8 to 18 carbon atoms and one contains an anionic hydrotropic group (such as carboxylate, sulfonate, sulfate, phosphate, or phosphonate); and mixtures of such materials.

[0113] Surfactants or mixtures of compatible surfactants can be present in the compositions of the present invention in amounts of 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.

[0114] Flavoring agent

[0115] The oral care compositions of the present invention can also include flavoring agents. Flavoring agents useful in the practice of the present invention include, but are not limited to, essential oils and various flavoring aldehydes, esters, alcohols, and the like, as well as sweetening agents 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. Chemical substances such as menthol, carvone, and anethole are also suitable. Some embodiments employ peppermint oil and spearmint.

[0116] The flavoring agent is incorporated into the oral composition at a concentration of from 0.01% to 1% by weight.

[0117] Chelating agent and anti-calculus agent

[0118] The oral care compositions of the present invention can also include 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.

[0119] Another group of agents suitable for use as chelating agents and anti-calculus agents in the present invention is soluble pyrophosphates. The pyrophosphates used in the compositions of the present invention can be any of the alkali metal pyrophosphates. In certain embodiments, the salts include tetra-alkali metal pyrophosphates, di-alkali metal dihydrogen pyrophosphates, tri-alkali metal monohydrogen pyrophosphates, and mixtures thereof, wherein the alkali metal is sodium or potassium. Both hydrated and unhydrated forms of the salts are suitable. The effective amount of pyrophosphate that can be used 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. Pyrophosphates also contribute to the preservation of the composition by reducing the activity of water.

[0120] 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-calculus agents include, but are not limited to, monophosphates (e.g., mono-basic phosphates, di-basic phosphates, or tri-basic phosphates) and P1-6 polyphosphates (e.g., pyrophosphates, tripolyphosphates, tetraphosphates, and metaphosphates), zinc salts (e.g., zinc citrate, zinc chloride, zinc citrate trihydrate), (copolymer of poly(vinyl methyl ether) (PVM) and maleic acid (MA)), poly(aminopropanesulfonic acid) (AMPS), polypeptides, polyolefin sulfonates, polyolefin phosphates, and diphosphonates. In certain embodiments, other anti-calculus agents are alkali metal and / or alkaline earth metal phosphates, such as sodium salts, potassium salts, or calcium salts. In certain embodiments, the composition includes monophosphates (e.g., mono-basic phosphates, di-basic phosphates, or tri-basic phosphates), P1-6 polyphosphates, Gantrez, or combinations thereof. Still in certain embodiments, the composition includes sodium tripolyphosphate, tetrasodium pyrophosphate, Gantrez, or combinations thereof.

[0121] Polymer

[0122] The oral care composition of the present invention also optionally comprises one or more polymers such as polyethylene glycol, copolymers of polyethylene 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.

[0123] Other polymers that are operative include those such as 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available, for example, as Monsanto EMA No. 1103, M.W. 10,000, and EMA grade 61; and 1:1 copolymers of acrylic acid with methyl methacrylate or hydroxyethyl methacrylate, methyl acrylate or ethyl acrylate, isobutyl vinyl ether, or N-vinyl-2-pyrrolidone.

[0124] Generally, suitable are polymeric ethylenically or olefinically unsaturated carboxylic acids containing an active carbon-carbon ethylenic double bond and at least one carboxyl group, i.e., acids containing ethylenic double bonds that are readily operative in polymerization because they are present in the monomer molecule in the α-β position relative to the carboxyl group or as part of a terminal methylene group. 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 the anhydrides. Other different ethylenic monomers copolymerizable with such carboxylic acid monomers include vinyl acetate, vinyl chloride, dimethyl maleate, etc. The copolymer contains carboxylate groups sufficient for water solubility.

[0125] Another class of aggregating agents includes compositions comprising homopolymers of substituted acrylamides and / or homopolymers of unsaturated sulfonic acids and their salts, particularly where the polymers are unsaturated sulfonic acids based on 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 June 27, 1989, which is incorporated herein by reference.

[0126] In the preparation of oral care compositions, it is sometimes necessary to add some thickening materials to provide a desirable consistency or to stabilize or enhance the performance of the formulation. In certain embodiments, the thickening agent is a carboxyvinyl polymer, 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 embodiments, a thickening agent is used in an amount of from about 0.5% to about 5.0% by weight of the total composition.

[0127] Abrasive

[0128] 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 generally ground limestone, which may optionally be refined or partially refined to remove impurities. For use in the present invention, the average particle size of the material is less than 10 microns, for example 3 - 7 microns, for example about 5.5 microns. For example, fine particle silica may have an average particle size (D50) of 2.5 - 4.5 microns. Since natural calcium carbonate can contain a high proportion of relatively large particles that are not carefully controlled, which would unacceptably increase the abrasiveness, preferably no more than 0.01% by weight, preferably no more than 0.004% by weight 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, for example about 1.2, for example 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 25 - 11FG.

[0129] 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 small, for example, 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 will not pass through a 325 mesh sieve. The particles may have, for example, a D50 of 3-6 microns, for example 3.8-4.9, for example about 4.3; a D50 of 1-4 microns, for example 2.2-2.6 microns, for example about 2.4 microns; and a D10 of 1-2 microns, for example 1.2-1.4, for example about 1.3 microns. The particles have a relatively high water absorbency, 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, 15Plus.

[0130] In certain embodiments, the present invention may include additional calcium-containing abrasives, such as calcium phosphate abrasives, such as tricalcium phosphate (Ca3(PO4)2), hydroxyapatite (Ca 10 (PO4)6(OH)2) or dicalcium phosphate dihydrate (CaHPO4·2H2O, sometimes also referred to herein as DiCal) or calcium pyrophosphate; and / or silica abrasives, sodium metaphosphate, potassium metaphosphate, aluminosilicate, calcined alumina, bentonite or other siliceous materials, or combinations thereof. Any silica suitable for use in oral care compositions may be used, such as precipitated silica or silica gel. For example, synthetic amorphous silica. Silica may also be used as a thickening agent, such as particulate silica. For example, the silica may also be small particulate silica (e.g., Sorbosil AC43 obtained from PQ Corporation, Warrington, United Kingdom). However, this additional abrasive is preferably not present in a type or amount that will increase the RDA of the dentifrice to a level that may damage sensitive teeth (e.g., greater than 130).

[0131] Water

[0132] Water is present in the oral compositions of the present invention (such as 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 generally makes up the balance of the composition and ranges from 5% to 45% by weight of the oral composition, such as 10% to 20% by weight, such as 25 - 35% by weight. 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 one measure for calculating the free water.

[0133] Humectant

[0134] In certain embodiments of the oral compositions (such as Composition 1.0 and the like), it is also desirable to incorporate humectants to reduce evaporation and also to aid in preservation by reducing the activity of water. Certain humectants may also impart a desirable sweetness or flavor to the composition. Humectants generally range from 15% to 70% by weight of the composition in one embodiment or 30% to 65% by weight in another embodiment, based on the pure humectant.

[0135] Suitable humectants include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, propylene glycol, and other polyols and mixtures of these humectants. A mixture of glycerin and sorbitol can be used in certain embodiments as the humectant component of the compositions herein.

[0136] The present invention, in its method aspect, relates to the oral administration of a safe and effective amount of the compositions described herein.

[0137] 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, clear pastes, gels, mouthwashes, sprays, and chewing gums.

[0138] The ranges used throughout are used as shorthand descriptions for each value within the stated range. Any value within the range can be selected as the range endpoint. Additionally, all references cited herein are hereby incorporated by reference in their entirety. If a conflict exists between the definitions in the present disclosure and those in the cited references, the present 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 the preparation, storage, and use of the actual formulation, and such products are intended to be covered by the described formulations.

[0139] The following examples further describe and confirm illustrative examples within the scope of the present invention. The examples are given for illustration only and should not be regarded as limiting the present invention, as many variations can be made 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.

[0140] Example 1

[0141] Table 1: Dentifrice formulation A

[0142]

[0143]

[0144] Example 2

[0145] Table 2: Stannous stability

[0146]

[0147]

[0148]

[0149] Example 3

[0150] Table 3 shows the buffering agent compositions used in Examples 1 - 3 above.

[0151] Table 3:

[0152]

[0153] The water concentration of the above formulations ranges from 17.0 wt% to 21.0 wt%. These are considered "high water" formulations. Thus, the applicant has solved the instability of stannous ions without using a) low water formulations or b) biphasic compositions.

[0154] Example 4

[0155] Table 4 - Stannous uptake in aerobic biofilms

[0156] (in (ppm))

[0157]

[0158]

[0159] *Numbers enclosed in parentheses indicate that a second experiment was conducted.

[0160] **The name "Trt" should be understood to mean "treatment".

[0161] ***"Buffer" refers to a 1.2 wt% organic acid buffer, which contains 1.0 wt% sodium citrate and 0.2 wt% citric acid. The wt% of sodium citrate and citric acid refers to their amounts relative to the entire composition.

[0162] The aerobic biofilm model quantifies the ability of a compound to prevent the maturation of a biofilm containing a saliva culture on an artificial tooth surface (or hydroxyapatite (HAP)) through repeated treatments over a 5-day period. On day 1, hydroxyapatite discs on the active attachment lid are incubated in clarified, sterile-filtered saliva to form a pellicle, treated, inoculated in whole human saliva suspended in a medium, and incubated, and then the treatment is repeated at the end of the day. On days 2 to 5, the treatment is repeated every morning.

[0163] After each treatment, each HAP disc containing the biofilm is transferred to a tube containing 1 ml of aqua regia, which is a mixture of nitric acid and hydrochloric acid, for metal dissolution or acid digestion. The tube is kept under a fume hood overnight to ensure complete acid digestion. The sample is centrifuged to precipitate debris. The acid supernatant (aqueous portion) is transferred to another clean tube and brought to volume with sterile water to prepare a 10% acid solution (1 ml supernatant: 9 ml water). This sample is sent to the analysis department for metal detection. The data are expressed as parts per million (ppm) and metal extraction for 6 treatments.

[0164] As can be seen from Table 4, the composition containing SnF and zinc phosphate shows a greatly increased stannous uptake in the aerobic biofilm assay compared to the commercially available main formulation containing zinc lactate as the zinc source and stannous fluoride as the stannous source.

Claims

1. An oral care composition comprising: a zinc source comprising zinc phosphate in an amount of 0.05 wt% to 10 wt%; a first stannous source comprising stannous fluoride; a second stannous source, wherein the second stannous source comprises stannous pyrophosphate in an amount of 0.1 wt% to 3 wt%; a citrate buffer system, wherein the citrate buffer system comprises trisodium citrate and citric acid; and water present in an amount of 15 wt% to 35 wt%; Among them, said wt% being based on the total weight of the oral care composition.

2. The oral care composition according to claim 1, wherein the zinc phosphate is a preformed salt of zinc phosphate.

3. The oral care composition according to claim 1 or 2, wherein the zinc phosphate is present in an amount sufficient to dissociate the stannous fluoride to provide a therapeutically effective amount of stannous ions in an aqueous solution.

4. The oral care composition according to claim 1, wherein the first stannous source further comprises one or a mixture of two or more of the following: stannous chloride dihydrate, stannous pyrophosphate, organic stannous carboxylates comprising stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate, stannous citrate, and stannous glyoxylate.

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

6. The oral care composition according to claim 1, wherein the composition further comprises one or a mixture of two or more of the following: disodium hydrogen phosphate, dipotassium hydrogen phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, disodium hydrogen orthophosphate, sodium dihydrogen phosphate, and pentapotassium triphosphate.

7. The oral care composition according to claim 6, wherein the composition comprises tetrapotassium pyrophosphate.

8. The oral care composition according to claim 6, wherein the composition comprises sodium tripolyphosphate.

9. The oral care composition according to claim 1, wherein the composition comprises: zinc phosphate in an amount of 1 wt%; stannous pyrophosphate in an amount of 0.2 wt%; and tetrasodium pyrophosphate in an amount of 2 wt%.

10. The oral care composition according to claim 1, wherein the composition comprises: zinc phosphate in an amount of 1 wt%; stannous pyrophosphate in an amount of 0.3 wt%; and tetrasodium pyrophosphate in an amount of 2 wt%.

11. The oral care composition according to claim 1, wherein the composition comprises: zinc phosphate in an amount of 1.7 wt%; stannous pyrophosphate in an amount of 1 wt%; and tetrasodium pyrophosphate in an amount of 2 wt%.

12. The oral care composition according to claim 1, further comprising one or more surfactants, wherein the total amount of the one or more surfactants is 0.1 wt% to 5 wt%.

13. The oral care composition according to claim 12, wherein the total amount of the one or more surfactants is 0.1 wt% to 3 wt%.

14. The oral care composition according to claim 12, wherein the one or more surfactants comprise one or a mixture of two or more of the following: sodium N-methyl-N-cocoyl taurate, sodium lauryl sulfate monoglyceride, sodium lauryl sulfate, sodium lauryl polyoxyethylene (2) ether sulfate, sodium lauryl benzenesulfonate, N-2-ethyl potassium laurate sulfoacetamide, and sodium lauroyl sarcosine.

15. Use of the oral care composition according to claim 1 in the preparation of a medicament for improving oral health 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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