Oral care composition

Abstract

The present invention relates to an oral care composition for treating or preventing aggressive tooth demineralization, plaque and dental caries. The oral care composition includes zinc lactate dihydrate, a source of stannous ions, at least one phosphate, and a buffer system.

Description

[0001] This application is a divisional application of a Chinese patent application filed on June 24, 2016, with application number "201680086969.2" and invention name "Oral Care Composition". Technical Field

[0002] The present invention relates to an oral care composition for treating or preventing erosive tooth demineralization, dental plaque and caries. The oral care composition comprises zinc lactate dihydrate, a stannous ion source, at least one phosphate, and a buffer system. Background Art

[0003] Dental plaque is a sticky biofilm or mass of bacteria commonly found between teeth, along the gum line, and below the gum line margins. Dental plaque can cause dental caries and periodontal problems such as gingivitis and periodontitis. Dental caries, or tooth demineralization, is caused by acids produced by bacterial degradation of fermentable sugars.

[0004] Oral care compositions containing stannous ion sources show excellent clinical benefits, particularly in reducing gingivitis and treating or preventing erosive tooth demineralization. However, it may be difficult to formulate oral care compositions with stannous ion sources. One reason is that stannous ions may be unstable and may react with other ingredients of the oral care composition to form insoluble, inactive tin compounds, thereby reducing the amount of available stannous ions in the composition. One method of overcoming the stannous ion stability problem is to limit the amount of water in the composition to very low levels, or to use a two-phase system. Both of these solutions to the stannous ion problem have disadvantages. Low moisture oral care compositions may be difficult to formulate with desired rheological properties, and two-phase compositions are significantly more expensive in manufacturing and packaging.

[0005]

[0006] Therefore, there is a need to provide improved stannous ion-containing products for use in treating or preventing erosion of tooth enamel, having antimicrobial efficacy, reducing dental plaque or treating or controlling gingivitis. Summary of the invention

[0006] Disclosed herein is an oral care composition comprising zinc lactate, a stannous ion source, at least one phosphate and a buffer system. Methods and uses of this composition are also described throughout. Compared to the prior art, the composition disclosed herein provides improved demineralization protection and enhanced antibacterial activity.

[0007] Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter.It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention. DETAILED DESCRIPTION

[0008] It has been unexpectedly discovered that formulations comprising zinc lactate, a stannous source, a phosphate, and a buffer system selected in specific concentrations and amounts are unexpectedly more effective in enhancing the anti-corrosion and antimicrobial properties of stannous ion-containing formulations than certain previous commercial products that may contain stannous fluoride and zinc lactate.

[0009] In one aspect, the present disclosure provides an oral care composition (Composition 1.0) comprising an orally acceptable carrier and:

[0010] a. Zinc lactate;

[0011] b. stannous ion source;

[0012] c. phosphates; and

[0013] d. Buffer system (eg, wherein the buffer comprises trisodium citrate and citric acid).

[0014] In other embodiments of the first aspect, the present disclosure further provides:

[0015] 1.1 Composition 1.1, wherein the zinc lactate is L-(+)-zinc lactate, D-(-)-zinc lactate, DL-zinc lactate, or a combination thereof.

[0016] 1.2 A composition according to any preceding claim, wherein the composition comprises zinc lactate dihydrate, for example, L-(+)-zinc lactate dihydrate.

[0017] 1.3 A composition according to any preceding claim, wherein the zinc lactate is present in an amount effective to prevent tooth erosion, caries and periodontal problems such as gingivitis and periodontitis.

[0018] 1.4 A composition according to any preceding claim, wherein the composition comprises 0.05 to 10% by weight, for example, 0.1% to 8%, 0.5% to 5%, 1% to 4%, 2% to 3%, or 2.5% by weight of the oral care composition.

[0019] 1.5 A composition according to any of the preceding claims, wherein the source of stannous ions comprises a stannous halide (e.g., stannous fluoride or stannous chloride), a stannous carboxylate (e.g., stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate or stannous citrate), stannous glycolate or a mixture thereof.

[0020] 1.6 According to any of the preceding compositions, the stannous ion source (e.g., stannous fluoride) is present in an amount of 0.01% to 5%, for example, 0.05% to 4%, 0.1% to 3%, 0.2% to 2%, 0.3% to 1%, 0.4% to 0,8%, 0.4% to 0.6% (e.g., or about 0.45% or about 0.454%) by weight of the oral care composition.

[0021] 1.7 Composition 1.5 or 1.6 wherein the zincous ion source is stannous fluoride.

[0022] 1.8 Composition 1.7, wherein the composition comprises stannous fluoride in an amount of 0.01 wt% to 5 wt%, such as 0.3% to 1% (eg, about 0.45% or about 0.454%), based on the total weight of the composition.

[0023] 1.9 According to any preceding composition, the composition further comprises a fluoride ion source.

[0024] 1.10 The composition according to 1.9, wherein the fluoride ion source is selected from the group consisting of stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride and combinations thereof.

[0025] 1.11 A composition according to 1.9 or 1.10, wherein the fluoride ion source is present in an amount of 0.01 to 5%, for example 0.1 to 3%, 0.2 to 2%, or 0.3 to 1% (e.g. 0.45%) based on the total weight of the composition.

[0026] 1.12 Compositions according to any preceding claim, wherein the phosphate comprises an orally acceptable monophosphate and / or polyphosphate, for example, 1-6 Phosphate, or P 1-4 Phosphates, such as orthophosphates (eg, monobasic orthophosphate, dibasic orthophosphate, or tribasic orthophosphate), pyrophosphates, tripolyphosphates, tetraphosphates, and hexaphosphates.

[0027] 1.13 Composition 1.12, wherein the phosphate is selected from the alkali metal salts of monobasic phosphates, dibasic or tribasic phosphates, and the alkali metal salts of polyphosphates, for example selected from sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, potassium tripolyphosphate and mixtures thereof.

[0028] 1.14 A composition according to 1.12 or 1.13, wherein the composition comprises phosphate in an amount of 0.5% to 15% by weight, such as 1% to 10% by weight, or 1% to 5% by weight (such as about 2% or about 3% by weight).

[0029] 1.15 According to any of the preceding compositions, wherein the composition comprises one or more pyrophosphates or tripolyphosphates, such as tetrasodium pyrophosphate (TSPP) and / or sodium tripolyphosphate (STPP), for example, wherein the amount of TSPP is from about 0.5 wt % to about 5 wt % (e.g., about 2 wt %), and / or wherein the amount of STPP is from 0.5 to 6 wt % (e.g., about 3 wt %), based on the weight of the composition.

[0030] 1.16 According to any of the preceding compositions, wherein the composition comprises TSPP and STPP, for example, based on the weight of the composition, wherein the amount of TSPP is from about 0.5 wt% to about 10 wt%, for example, 0.5 wt% to 5 wt%, or 1 wt% to 3 wt%, or about 2 wt%; and the amount of STPP is from 0.5 to 10 wt%, for example, 0.5 to 6 wt%, or 2-4 wt%, or about 3 wt%.

[0031] 1.17 According to any preceding embodiment, wherein the composition does not contain phosphates with more than four phosphate groups (eg, does not contain hexaphosphate or hexametaphosphate).

[0032] 1.18 According to any of the preceding compositions, wherein the composition comprises one or more alkali metal orthophosphates, one or more alkali metal pyrophosphates and / or one or more alkali metal tripolyphosphates as the sole phosphate, for example, a mixture of one or more of sodium phosphate (monobasic, dibasic or tribasic), tetrasodium pyrophosphate and trisodium polyphosphate as the sole phosphate.

[0033] 1.19 A composition according to any preceding claim, wherein the only phosphates are alkali metal pyrophosphates and alkali metal tripolyphosphates, for example, sodium pyrophosphate and sodium tripolyphosphate.

[0034] 1.20 According to any preceding composition, wherein the composition comprises an aqueous buffer system, for example wherein the buffer system comprises an organic acid and an alkali metal salt thereof, for example wherein the organic acid is citric acid and the salt is a mono-, di- and / or tri-alkali metal citrate salt, for example a mono-, di- and / or tri-lithium, sodium, potassium or cesium citrate salt and citric acid. For example, wherein the composition comprises 1-10 wt % of the organic acid salt and 0.1-5 wt % of the organic acid.

[0035] 1.21 A composition according to 1.20 wherein the buffer system comprises a citric acid buffer, wherein the citric acid buffer comprises trisodium citrate and citric acid (e.g. 1 to 10% by weight of the composition), for example wherein the molar ratio of mono-, di- and / or trisodium citrate and citric acid is 1.5 to 5 (e.g. 2 to 4). The buffer system may be present in an amount by weight greater than the amount by weight of the source of stannous ions.

[0036] 1.22 According to any preceding composition, wherein the pH of the composition is from 5 to 8, such as from 6 to 8, or from 6 to 7, or from 7 to 8.

[0037] 1.23 A composition according to any preceding claim, wherein the composition comprises water in an amount of 10 to 40% by weight, such as 10-30%, or 10-20%, or 10-15% (eg 12.7% by weight), by weight of the oral care composition.

[0038] 1.24 According to any of the preceding compositions, it further comprises one or more of the following: abrasives, silica abrasives, surfactants, foaming agents, vitamins, polymers, enzymes, humectants, thickeners, other antimicrobial agents, preservatives, foaming agents, sweeteners (such as saccharin sodium), flavoring agents, aesthetic agents, coloring agents, and / or combinations thereof.

[0039] 1.25 A composition according to any preceding claim, wherein the composition comprises 0.5-5% zinc lactate, 0.05-3% stannous fluoride, and 0.5-10% phosphate, by weight of the composition, and a buffer system.

[0040] 1.26 A composition according to any preceding claim, wherein the composition comprises:

[0041] a. About 2.5 zinc lactate

[0042] b. About 3.6% citrate buffer (e.g., wherein the buffer is about 3.0% trisodium citrate and 0.6% citric acid)

[0043] c. About 0.45% stannous fluoride (e.g., about 0.454%)

[0044] d. about 3% sodium tripolyphosphate (STPP); and

[0045] e. About 2% tetrasodium pyrophosphate (TSPP).

[0046] 1.27 A composition according to any preceding claim, wherein the composition is substantially free of hexametaphosphate (eg, sodium hexametaphosphate).

[0047] 1.28 According to any preceding composition, wherein the composition contains no phosphate with more than four phosphate groups or contains no phosphate with more than three phosphate groups.

[0048] 1.29 A composition according to any preceding claim, wherein the composition comprises sodium tripolyphosphate and tetrasodium pyrophosphate as the only phosphate compounds.

[0049] 1.30 A composition according to any preceding claim, wherein the composition comprises from about 0.05 to 3% zinc ions, such as from 0.1 to 1%, or from 0.25 to 0.75%, or about 0.6% zinc ions by weight of the composition.

[0050] 1.31 According to any preceding composition, wherein the composition does not further comprise zinc citrate, zinc phosphate or zinc oxide.

[0051] 1.32 A composition according to any preceding claim, wherein zinc lactate is the only source of zinc present.

[0052] 1.33 A composition according to any preceding claim, which is a single phase composition (eg, not a two phase composition).

[0053] 1.34 A composition according to any of the preceding claims, which, when applied to the oral cavity (e.g. by rinsing, optionally in combination with brushing), is effective in: (i) reducing or inhibiting caries formation, (ii) reducing, repairing or inhibiting early caries lesions of tooth enamel, for example, as detected by quantitative light induced fluorescence (QLF) or electrical caries measurement (ECM), (iii) reducing or inhibiting demineralization and promoting remineralization of teeth, (iv) reducing allergic reactions in teeth, (v) reducing or inhibiting gingivitis, (vi) promoting the healing of herpes or cuts in the mouth, (vii) reducing the level of acid-producing bacteria, (viii) reducing the level of acid-producing bacteria, ) increase the relative abundance of arginine-degrading bacteria, (ix) inhibit microbial biofilm formation in the oral cavity, (x) increase and / or maintain plaque pH at a level of at least pH 5.5 after a sugar challenge, (xi) reduce plaque accumulation, (xii) treat, relieve or reduce dry mouth, (xiii) clean teeth and the oral cavity, (xiv) reduce corrosion, (xv) prevent 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 potential for systemic infection via oral tissues.

[0054] 1.35 An oral composition according to any preceding claim, wherein the oral composition is a toothpaste or dentifrice, a mouthwash or mouth rinse, a topical oral gel, and a denture cleanser.

[0055] 1.36 A composition obtained or obtainable by combining the ingredients set out in any one of the preceding compositions.

[0056] 1.37 A composition for use as described in any of the preceding compositions.

[0057] In another aspect, the present disclosure provides a method for improving oral health, comprising applying an effective amount of an oral composition of any one of the embodiments described herein (e.g., any one of composition 1.0 et seq.) to the oral cavity of a subject in need thereof, for example, for the following method

[0058] i. Reduce or inhibit the formation of dental caries,

[0059] ii. reducing, repairing or inhibiting early caries lesions of tooth enamel, e.g., as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM),

[0060] iii. Reduce or inhibit demineralization and promote remineralization of teeth,

[0061] iv. Reduce tooth allergy,

[0062] v. Reduce or inhibit gingivitis,

[0063] vi. Promote the healing of ulcers or cuts in the mouth,

[0064] vii. Reduce the content of acid-producing bacteria,

[0065] viii. Increase the relative content of bacteria that decompose arginine,

[0066] ix. Inhibit the formation of microbial biofilm in the oral cavity,

[0067] x. Raising and / or maintaining the pH of dental plaque at a level of at least pH 5.5 after sugar challenge,

[0068] xi. Reduce plaque accumulation,

[0069] xii. Treat dry mouth,

[0070] xiii. Enhance systemic health, including cardiovascular health, for example by reducing the likelihood of systemic infection through oral tissues,

[0071] xiv. Whiten teeth,

[0072] xv. Reduce tooth erosion,

[0073] xvi. Immunize (or protect) teeth against cariogenic bacteria and their effects, and / or

[0074] xvii. Clean teeth and mouth.

[0075] As used herein, "phosphate" encompasses orally acceptable monophosphates and polyphosphates.

[0076] As used herein, the term "antibacterial activity" means activity as determined by any recognized in vitro or in vivo antibacterial assay or test.

[0077] Water: The water used to prepare the oral composition according to the present disclosure can be deionized (sometimes referred to as demineralized water) and / or free of organic impurities. As used herein, the amount of water in the composition includes the free water added plus the amount of water introduced with other materials. The composition can contain water in an amount of 10% to 40% by weight, such as 10-30%, or 10-20%, or 10-15%; (e.g., 12.7% by weight) based on the weight of the oral care composition. In a specific embodiment, the oral care composition of the present disclosure contains 12.7% by weight of water, which is composed of 8.7% free water and water included in other added ingredients, such as Gantrez, cocamidopropyl betaine (CAPB), and glycerin.

[0078] Fluoride source: In various embodiments of the present disclosure, the composition further comprises a fluoride ion source. This fluoride ion source can be in addition to any stannous fluoride present. Suitable fluoride ion sources include, but are not limited to, stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluorides, ammonium fluoride, and combinations thereof. Examples of suitable fluoride-producing materials are found in U.S. Pat. No. 3,535,421 to Briner et al.; and U.S. Pat. No. 3,678,154 to Widder et al., the disclosures of each of which are incorporated herein by reference in their entirety.

[0079] Tartar control agent: In various embodiments of the present disclosure (e.g., Composition 1.0 et seq.), the composition further comprises one or more anti-tartar agents (tartar control agents). Suitable anti-tartar agents include, but are not limited to, monophosphates (e.g., monobasic phosphates, dibasic phosphates, or tribasic phosphates) and P 1-6 Polyphosphates (e.g. pyrophosphate, tripolyphosphate, tetraphosphate and hexametaphosphate), (copolymer of methyl vinyl ether (PVM) and maleic acid (MA)), polyaminopropanesulfonic acid (AMPS), polypeptides, polyolefin sulfonates, polyolefin phosphates and bisphosphonates. In certain embodiments, other anticalculus agents are alkali metal and / or alkaline earth metal phosphates, such as sodium, potassium or calcium salts. In certain embodiments, the composition includes monophosphates (e.g., monobasic phosphates, dibasic phosphates or tribasic phosphates), P1-6 polyphosphates, Gantrez or combinations thereof. Still in certain embodiments, the composition includes sodium tripolyphosphate, tetrasodium pyrophosphate, Gantrez or combinations thereof.

[0080] Abrasive: The compositions of the present disclosure (e.g., Composition 1.0 et seq.) may include an abrasive. Examples of suitable abrasives include silica abrasives, such as standard cleaning silica, high cleaning silica, synthetic grinding silica, or any other suitable abrasive silica. Other examples of abrasives that may be used in addition to or in place of silica abrasives include phosphate 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 referred to herein as DiCal), calcium pyrophosphate, sodium metaphosphate or potassium metaphosphate; calcium carbonate abrasive; or abrasives such as anhydrous alumina trihydrate, aluminum silicate, calcined alumina, bentonite or other siliceous materials or combinations thereof. The abrasive is generally present in the composition of the present invention at a concentration of about 10 to about 40 weight percent and preferably about 15 to about 20 or about 30 weight percent.

[0081] Wetting agent: In certain embodiments of the oral composition, it is also desirable to incorporate a wetting agent to prevent the composition from hardening after exposure to air. Suitable wetting agents include glycerine, sorbitol, propylene glycol, and polyethylene glycol (e.g., polyethylene glycol with a molecular weight in the range of 200-8000), as well as mixtures of other polyols and these wetting agents. In one embodiment of the present disclosure, the main wetting agent is one of glycerine, sorbitol, polyethylene glycol, and propylene glycol. Based on the gross weight of the composition, one or more wetting agents can be greater than about 25 wt %, such as about 25 wt % to about 55 wt %, or about 30 wt % or about 40 wt % to about 50 wt % content.

[0082] Polymer: In certain embodiments of the oral composition (e.g., composition 1.0 et seq.), a polymer is included to adjust the viscosity of the formulation or to enhance the solubility of other ingredients. Such polymers include polyethylene glycol, polysaccharides (e.g., cellulose derivatives, such as hydroxymethylcellulose (CMC), microcrystalline 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 completely neutralized water-soluble alkali metals (e.g., potassium and sodium) or ammonium salts. In one embodiment, the oral care composition can contain polyvinylpyrrolidone (PVP). PVP generally refers to a polymer containing vinylpyrrolidone (also referred to as N-vinylpyrrolidone, N-vinyl-2-pyrrolidone, and N-vinyl-2-pyrrolidone) as a monomer unit.

[0083] The compositions of the present disclosure (e.g., composition 1.0 et seq.) may include anionic polymers (e.g., as antimicrobial enhancers), e.g., in an amount of 0.05 to 5%. Examples of such agents are disclosed in U.S. Pat. Nos. 5,188,821 and 5,192,531, the contents of which are incorporated herein by reference in their entirety. These polymers include synthetic anionic polymeric polycarboxylates, such as 1:4 to 4:1 copolymers of maleic anhydride or maleic acid and another polymerizable ethylenically unsaturated monomer, preferably methyl vinyl ether / maleic anhydride. Preferably, the copolymer has a molecular weight (MW) of 30,000 to 1,000,000, such as 300,000 to 800,000. These copolymers are available, for example, as Gantrez, for example, AN 139 (MW 500,000), AN 119 (MW 250,000) and S-97 pharmaceutical grade (MW 700,000) available from ISP Technologies, Bound Brook, NJ08805. The polymer, when present, is present in an amount ranging from about 0.05 to about 3% by weight. Other polymers that work include, for example, those of 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or ethylene, the latter being available, for example, with Monsanto EMA No. 1103, MW 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. Generally speaking, suitable are polymeric olefinic or olefinic unsaturated carboxylic acids containing an active carbon-carbon olefinic double bond and at least one carboxyl group, i.e., acids containing olefinic double bonds that are easily effective 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, ethacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloxypropionic acid, sorbic acid, α-chlorosorbic acid, cinnamic acid, β-styryl acrylic acid, mucofuric acid, itaconic acid, citraconic acid, methyl fumaric acid, glutaconic acid, aconitic acid, α-phenyl acrylic acid, 2-benzyl acrylic acid, 2-cyclohexyl acrylic acid, angelic acid, umbelliferous acid, fumaric acid, maleic acid, and anhydrides. Other different olefinic monomers that can be copolymerized with such carboxyl monomers include vinyl acetate, vinyl chloride, dimethyl maleate, etc. The copolymer contains sufficient carboxyl salt groups for water solubility.Another class of polymerizing agents includes compositions containing homopolymers of substituted acrylamides and / or homopolymers of unsaturated sulfonic acids and salts thereof, particularly where the polymer is based on an unsaturated sulfonic acid selected from acrylamidoalkylsulfonic acids (e.g., 2-acrylamido-2-methylpropanesulfonic acid) having a molecular weight of 1,000 to 2,000,000, as described in U.S. Pat. No. 4,842,847, issued to Zahid on June 27, 1989, which is incorporated herein by reference in its entirety. Another class of suitable polymerizing agents includes polyamino acids containing proportions of anionic surface-active amino acids, such as aspartic acid, glutamic acid, and phosphoserine, for example, as described in U.S. Pat. No. 4,866,161 issued to Sikes et al., which is also incorporated herein by reference in its entirety.

[0084] Thickeners: Thickeners or gelling agents may be included in the compositions (e.g., Composition 1.0 et seq.). Suitable examples of thickeners are carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose, and water-soluble salts of cellulose ethers, such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums, such as gum karaya, gum arabic, and gum tragacanth may also be incorporated. Colloidal magnesium aluminum silicate may also be used as a component of the thickening composition to further improve the texture of the composition. Silica that forms a polymer structure or gel in an aqueous medium may be present. It should be noted that these silica thickeners are physically and functionally distinct from the particulate silica abrasive also present in the composition, because the silica thickeners are very finely dispersed and provide little or no abrasive action. In certain embodiments, the thickener is present in an amount of about 0.1 to about 15%; about 0.2, about 0.3, or about 0.4 to about 10%; about 0.5% to about 1, about 2, about 3, about 4, or about 5% by weight of the total composition used.

[0085] Surfactants: Surfactants (surface active agents) can be incorporated into the oral compositions (e.g., Composition 1.0 et seq.) to provide foaming properties, as well as to help produce a uniform composition, wherein the composition is evenly distributed. Surfactants can be anionic, cationic, or zwitterionic (amphoteric) in nature. In some embodiments, mixtures of surfactants are used, such as mixtures of surfactants of different properties. In general, suitable surfactants are those that are reasonably stable over a wide pH range.

[0086] Suitable examples of anionic surfactants are water-soluble salts of monosulfated monoglycerides of higher fatty acids, such as sodium salts of monosulfated monoglycerides of hydrogenated coconut fatty acids, such as sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride sulfate; higher alkyl sulfates, such as sodium lauryl sulfate; higher alkyl ether sulfates, for example, of the formula CH3(CH2)m CH2(OCH2CH2) n OS03X, wherein m is 6-16, such as 10, n is 1-6, such as 2, 3 or 4, and X is Na or K, such as sodium lauryl ether sulfate; higher alkyl aryl sulfonates, such as sodium dodecylbenzene sulfonate (sodium lauryl benzene sulfonate) and sodium dodecylbenzene sulfonate; higher alkyl sulfoacetates, such as sodium lauryl sulfoacetate (sodium dodecylbenzene sulfonate), higher fatty acid esters of 1,2-dihydroxypropane sulfonic acid, sulfolaurate (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl sarcosinate. "Higher alkyl" means, for example, C 6-30 Alkyl. In certain embodiments, anionic surfactants useful herein include water-soluble salts of alkyl sulfates having 10 to 18 carbon atoms in the alkyl group and water-soluble salts of sulfonated monoglycerides of fatty acids having 10 to 18 carbon atoms. Sodium lauryl sulfate, sodium lauroyl sarcosinate, and sodium coconut monoglyceride sulfonate are examples of this type of anionic surfactant. In a specific embodiment, the anionic surfactant is selected from sodium lauryl sulfate and sodium lauryl ether sulfate. In a specific embodiment, the composition of the present disclosure comprises sodium lauryl sulfate. One or more anionic surfactants can be present in an effective amount (e.g., > about 0.01% by weight of the formulation), but not in an amount (e.g., less than 10%) that will irritate the oral tissue, and the optimal concentration depends on the specific formulation and the specific surfactant. In one embodiment, one or more anionic surfactants are present in a toothpaste at about 0.3% by weight to about 4.5% by weight, such as about 0.5, 1 to about 2, 3, or 4% by weight, such as about 1.84% by weight, by the total weight of the composition. The compositions of the present disclosure may optionally contain a mixture of surfactants, for example, comprising anionic surfactants and other surfactants which may be anionic, cationic, zwitterionic or nonionic, such as cocamidopropyl betaine.

[0087] Examples of water-soluble nonionic surfactants are the condensation products of ethylene oxide with various hydrogen-containing compounds which react with ethylene oxide and have long hydrophobic chains (e.g., aliphatic chains of about 12 to 20 carbon atoms), the condensation products ("ethamers") containing hydrophilic polyoxyethylene moieties, such as the condensation products of poly(ethylene oxide) with fatty acids, fatty alcohols, fatty amides, and other fatty moieties, and with propylene oxide and polypropylene oxide (e.g., Pluronic materials).

[0088] Surfactants are more fully described in, for example, US Pat. Nos. 3,937,807 to Haefele; and 4,051,234 to Gieske et al., the disclosures of which are incorporated herein by reference in their entireties.

[0089] Whitening agent: In some embodiments, the dentifrice composition of the present disclosure includes a whitening agent. Whitening agents suitable for use in the present invention (e.g., composition 1.0 et seq.) may include any therapeutically effective agent suitable for use in the oral cavity. Suitable whitening agents include, but are not limited to, titanium dioxide, hydrogen peroxide, sodium tripolyphosphate, and the like. In one embodiment, the composition of the present invention further includes titanium dioxide and / or sodium tripolyphosphate.

[0090] Pigments and dyes: Other components that may be incorporated into the dentifrices of the present disclosure (e.g., Composition 1.0 et seq.) include pigments and dyes. In tooth formulations, the pigments and dyes may be titanium dioxide coated mica and / or FD. & C grade dyes. The proportion of pigment will generally be in the range of about 0.05 wt. % to about 3 wt. %, preferably about 0.1 wt. % to about 1.0 wt. %. FD. & C grade dyes may be used in an appropriate amount to provide the desired color, e.g., from about 0.0001 to about 0.05 wt. %, such as about 0.002 wt. %.

[0091] Flavoring: The oral care compositions of the present disclosure (e.g., composition 1.0 et seq.) may also include flavorings. Suitable flavorings include, but are not limited to, essential oils and various flavored aldehydes, esters, alcohols, and the like. Examples of essential oils include oils of spearmint, peppermint, holly, sassafras, cloves, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Other suitable flavorings include such chemicals as menthol, carbomer, and anethole. Certain embodiments employ peppermint oil and spearmint oil. Flavorings may be incorporated into the oral composition at a concentration of about 0.1 to about 5% by weight, e.g., about 0.5 to about 2.5% by weight.

[0092] Compositions according to the present invention can be prepared in suitable dentifrice bases such as comprising abrasives (such as silica abrasives), surfactants, foaming agents, vitamins, polymers, enzymes, humectants, thickeners, other antimicrobial agents, preservatives, foaming agents, sweeteners (such as sodium saccharin), flavoring agents, aesthetic agents, coloring agents and / or combinations thereof. Examples of suitable dentifrice bases are known in the art. Alternatively, the composition can be formulated into a gel (for example, used in a dental tray). These and other optional components are further described in U.S. Patent No. 5,004,597 to Majeti, U.S. Patent No. 3,959,458 to Agricola et al., and U.S. Patent No. 3,937,807 to Haefele, all of which are incorporated herein by reference in their entirety.

[0093] The present application further discloses a method for treating or preventing erosion of tooth enamel, dental plaque and gingivitis using the compositions described herein. The method comprises applying any composition as described herein to the teeth, for example, by brushing or otherwise applying the composition to the oral cavity of a subject in need. The composition can be applied regularly, for example, once or more times a day. In various embodiments, applying the composition of the present disclosure to a patient can provide one or more of the following benefits: (i) reducing hypersensitivity of the teeth, (ii) reducing plaque accumulation, (iii) reducing or inhibiting demineralization and promoting remineralization of the teeth, (iv) inhibiting microbial biofilm formation in the oral cavity, (v) reducing or inhibiting gingivitis, (vi) promoting the healing of herpes or cuts in the mouth, (vii) reducing the content of acid-producing bacteria, (viii) increasing the relative content of non-caries and / or non-plaque-forming bacteria, (ix) ) reduce or inhibit caries formation, (x) reduce, repair or inhibit early caries lesions of tooth enamel, for example, as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM), (xi) treat, alleviate or reduce dry mouth, (xii) clean teeth and oral cavity, (xiii) reduce erosion, (xiv) whiten teeth; (xv) reduce tartar accumulation, and / or (xvi) promote systemic health, including cardiovascular health, for example, by reducing the potential for systemic infection via oral tissue. The present disclosure further provides compositions for use in any of the above methods. Other embodiments provide methods wherein at least one tooth is remineralized after application of a composition as described herein.

[0094] Examples

[0095] Example 1: Recipe composition

[0096] Representative formulations

[0097] Element weight% Moisturizer 25-55 (e.g. 47) Abrasive 30-40 (e.g. 24) Purified water (free) 5-15 (e.g. 9) Organic acid salts (e.g., trisodium citrate) 1-10 (e.g. 3.0) Sodium tripolyphosphate 0.5-15 (e.g. 3.0) L-Lactate Zinc Dihydrate 0.05-10 (e.g. 2.5) Flavoring and coloring agents 1-10 (e.g. 2.9) Tetrasodium pyrophosphate 0.5-15 (e.g. 2.0) Anionic surfactants 0.01-10 (e.g. 1.8) polymer 0.05-5 (e.g. 1.85) Amphoteric surfactant 0.01-10 (e.g. 1.00) Thickener 0.1-15 (e.g. 1.6) Organic acids (such as citric acid) 0.1-5 (e.g. 0.60) Stannous fluoride 0.454

[0098] Example 2: Demineralization / Remineralization Study

[0099] Provided below is an exemplary composition of the present invention (Example 2), as well as a control, and a demineralization / remineralization study of two comparative commercial compositions (Comparison A, Comparison B). The control composition is the same as Example 2, except that it contains 0.12% stannous fluoride instead of 0.454% stannous fluoride. Comparison composition A is a commercial toothpaste formulation containing sodium fluoride but not containing stannous or zinc ion agents. Composition B is a commercial toothpaste formulation, which includes stannous fluoride, zinc lactate and sodium hexametaphosphate. Both commercial comparative compositions do not contain any carboxylic acid buffer system. The formulas of Example 2 and Composition B are shown in Table 2 below.

[0100] Table 2

[0101] Element Example 2 Comparison B Water and trace ingredients (colorants, flavorings) 11.74 9.50 Stannous fluoride 0.454 0.454 Zinc lactate 2.50 2.50 Thickener 2.65 3.15 glycerin 39.69 34.65 Abrasive Silica 24.00 20.00 Sodium Hexametaphosphate -- 13.00 Propylene glycol 4.00 7.00 Trisodium citrate dihydrate 3.00 -- Sodium tripolyphosphate 3.00 -- Polyethylene glycol 600 3.00 7.00 Tetrasodium pyrophosphate 2.00 -- Anionic surfactants 1.75 1.00 Trisodium phosphate -- 1.10 Amphoteric surfactant 1.00 -- Sodium Gluconate -- 0.65 Anionic polymer 0.61 -- Citric Acid 0.60 --

[0102] The dentifrice of Example 2, a control sample and two comparative examples were tested. During the demineralization / remineralization study, all samples were obtained by a 10-day pH cycle protocol. Overall, the teeth were immersed in heated saliva overnight to form a pellicle. The teeth were then treated twice a day with a 1:2 toothpaste: water slurry and three 2-minute acid challenges were performed using a 1.0% citric acid solution. Confocal microscopy was used to quantify the demineralization of tooth enamel. The results are shown in Table 3 below:

[0103] Table 3

[0104]

[0105] Teeth treated with the dentifrice composition of Example 2 showed only 21.63% mineral loss, while untreated (control) teeth exhibited 75.56% mineral loss, and teeth treated with Comparative A and Comparative B exhibited 71.29% and 53.12% mineral loss, respectively. Thus, the dentifrice composition of Example 2 exhibits enhanced protection against mineral loss compared to prior art compositions.

[0106] Example 3: Antimicrobial testing

[0107] The antimicrobial properties of the dentifrice compositions of Example 2 and Comparative Examples were investigated in an anaerobic biofilm model containing Gram-negative anaerobic bacteria on agar enriched with nalidixic acid and vancomycin. Bacterial cultures were grown on hydroxyapatite (HAP) disks under anaerobic conditions to first grow a biofilm. The disks were then treated with the test composition twice a day for five days, also under anaerobic conditions. On the fifth day, the HAP disks were treated only once to allow regeneration of the biofilm. The HAP disks were then coated with 5% sheep blood and the colonies were left overnight to grow. The colonies were then counted and reported as log 10Colony forming units / mL (CFU / mL). The results are shown in Table 3 below.

[0108] As illustrated by the data set forth in Table 4, exemplary compositions of the present disclosure exhibited greater antimicrobial efficacy than comparative compositions. Test formulation A was statistically significantly better than comparative commercial compositions B, C, and D in inhibiting bacterial growth during the test period.

[0109] Table 4

[0110] Composition <![CDATA[Log after 8 days 10 CFU / ml]]> Example 2 4.29 Comparison D 5.40 Comparison C 5.29 Comparison B 5.56

[0111] Comparative composition B is a commercial comparative composition used in the above-mentioned mineral loss test. Comparative compositions C and D are commercial compositions similar to B, each of which also contains 0.454% stannous fluoride, 2.5% zinc lactate and sodium hexametaphosphate, and which also lack the carboxylic acid buffer system.

[0112] As used throughout, ranges are used as a shorthand way of describing each value within a range. Any value within a range may be selected as a range endpoint. In addition, all references cited herein are hereby incorporated by reference in their entirety. If a definition in the present disclosure conflicts with a definition in a cited reference, the present disclosure shall prevail.

[0113] Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in this specification should be understood to refer to percentages by weight. The amounts given are based on the effective weight of the material.

[0114] While the invention has been described with reference to embodiments, it will be apparent to those skilled in the art that various modifications and changes may be made therein without departing from the scope of the invention as defined by the appended claims.

[0115] The present invention also relates to, for example, the following technical solutions:

[0116] 1. An oral care composition comprising an orally acceptable carrier and:

[0117] Zinc lactate;

[0118] Stannous ion source;

[0119] Phosphates; and

[0120] Buffer system.

[0121] 2. The oral care composition according to item 1, wherein the zinc lactate is zinc lactate dihydrate.

[0122] 3. An oral care composition according to any preceding clause, wherein the composition comprises zinc lactate in an amount of from 0.05% to 10% by weight of the composition.

[0123] 4. An oral care composition according to any of the preceding items, wherein the stannous ion source comprises stannous fluoride, stannous chloride, stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate, stannous citrate, stannous glycolate or a mixture thereof.

[0124] 5. The oral care composition according to any of the preceding items, further comprising a fluoride ion source.

[0125] 6. An oral care composition according to any preceding clause, wherein the source of stannous ions comprises stannous fluoride.

[0126] 7. An oral care composition according to any preceding clause, wherein the stannous ion source is present in an amount of 0.01% to 5% by weight of the oral care composition.

[0127] 8. An oral care composition according to any of the preceding items, wherein the phosphate is selected from the group consisting of alkali metal phosphates having one to six phosphate groups.

[0128] 9. An oral care composition according to any of the preceding items, wherein the phosphate is selected from disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, potassium tripolyphosphate, potassium tripolyphosphate, and mixtures thereof.

[0129] 10. An oral care composition according to any of the preceding clauses, wherein the phosphate is selected from tetrasodium pyrophosphate and / or sodium tripolyphosphate.

[0130] 11. An oral care composition according to any preceding clause, wherein the zinc phosphate is present in an amount of from 0.5% to 15% by weight of the oral care composition.

[0131] 12. An oral care composition according to any of the preceding items, wherein the buffer system comprises at least one of an organic acid or an alkali metal salt thereof.

[0132] 13. The composition according to item 12, wherein the organic acid is citric acid.

[0133] 14. A composition according to claim 12, wherein the buffer system comprises

[0134] A mixture of citric acid and trisodium citrate.

[0135] 15. An oral care composition according to any preceding clause, wherein the amount of water is from 10 to 40% by weight of the oral care composition.

[0136] 16. An oral care composition according to any preceding clause, which is a single phase composition.

[0137] 17. An oral care composition according to any one of the preceding clauses, wherein the composition comprises:

[0138] 0.5 to 5 wt % zinc lactate;

[0139] 0.05 to 3 wt % stannous fluoride;

[0140] 0.5 wt % to 10 wt % of one of the phosphates; and

[0141] Buffer system.

[0142] 18. An oral care composition according to any one of the preceding clauses, wherein the composition comprises:

[0143] a) About 2.5% zinc lactate

[0144] b) about 3.6% citrate buffer;

[0145] c) about 0.45% stannous fluoride;

[0146] d) about 3% sodium tripolyphosphate (STPP); and

[0147] e) About 2% tetrasodium pyrophosphate (TSPP).

[0148] 19. An oral care composition according to any one of the preceding items, wherein the oral care composition is a toothpaste or a tooth gel.

[0149] 20. A method of treating or reducing enamel erosion, dental plaque and caries comprising applying a composition according to any of the preceding items to the oral cavity of a subject in need thereof.

Claims

1. An oral care composition comprising: Zinc lactate, in an amount of about 2 wt % to 3 wt % based on the total weight of the oral care composition; Stannous source; Phosphates; Anionic polymers; A carboxylic acid buffer system; and Propylene glycol.

2. The oral care composition according to claim 1, wherein The propylene glycol is present in an amount of about 4 wt %, based on the total weight of the oral care composition.

3. The oral care composition according to claim 1, wherein The zinc lactate is zinc lactate dihydrate.

4. The oral care composition according to claim 1, wherein The amount of water is 10 wt% to 40 wt% based on the total weight of the oral care composition.

5. The oral care composition according to claim 1, wherein The stannous ion source comprises stannous fluoride, stannous chloride, stannous formate, stannous acetate, stannous gluconate, stannous lactate, stannous tartrate, stannous oxalate, stannous malonate, stannous citrate, stannous glycolate or a mixture thereof.

6. The oral care composition of claim 1, further comprising a fluoride ion source.

7. The oral care composition of claim 1, wherein the phosphate is selected from the group consisting of alkali metal phosphates having one to six phosphate groups.

8. The oral care composition of claim 1, wherein the phosphate is selected from disodium hydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, potassium tripolyphosphate, and mixtures thereof.

9. The oral care composition according to claim 1, wherein the phosphate is selected from tetrasodium pyrophosphate and / or sodium tripolyphosphate.

10. The oral care composition according to claim 1, wherein The phosphate is present in an amount of 0.5 wt % to 15 wt % based on the total weight of the oral care composition.

11. The oral care composition of claim 1, wherein the buffer system comprises at least one of an organic acid or an alkali metal salt thereof.

12. The oral care composition of claim 11, wherein the organic acid is citric acid.

13. The oral care composition of claim 11, wherein the buffer system comprises a mixture of citric acid and trisodium citrate.

14. The oral care composition of claim 1 which is a single phase composition.

15. The oral care composition of claim 1, wherein the composition comprises: 0.5 to 5 wt % zinc lactate; 0.05 wt % to 3 wt % stannous fluoride; and 0.5 wt. % to 10 wt. % of a phosphate, wherein all weight percentages are based on the total weight of the oral care composition.

16. The oral care composition of claim 1, wherein the composition comprises: About 2.5% by weight zinc lactate about 3.6% by weight citrate buffer; about 0.45 weight percent stannous fluoride; about 3% by weight sodium tripolyphosphate; and About 2 weight percent tetrasodium pyrophosphate, wherein all weight percents are based on the total weight of the oral care composition.

17. The oral care composition of claim 1, wherein the oral care composition is a toothpaste or a tooth gel.

18. An oral care composition, consisting of: an orally acceptable carrier, and: Zinc lactate, in an amount of about 2 wt % to 3 wt % based on the total weight of the oral care composition; Stannous ion source; Phosphates; Anionic polymers; Carboxylic acid buffer system; about 4% by weight propylene glycol; Optionally, one or more anionic surfactants; Optionally, one or more zwitterionic surfactants; Optionally, one or more thickeners; Optionally, one or more humectants; Optionally, one or more abrasives; Optionally, one or more flavoring and / or coloring agents; and / or Optionally, one or more antimicrobial agents.

19. A method of treating or reducing tooth enamel erosion, dental plaque and caries comprising applying the composition of claim 1 to the oral cavity of a subject in need thereof.

20. Use of the oral care composition of claim 1 in the manufacture of a medicament for use in a method of treating or reducing enamel erosion, dental plaque and caries comprising administering the medicament to the oral cavity of a subject in need thereof.

Images