Oral care composition

Abstract

This application provides, in particular, novel aqueous oral care compositions that can be used to combine and deliver poorly compatible ingredients, especially chlorhexidine and polyphosphates, by formulating the compositions with surfactants.

Description

Background Technology

[0001] This application particularly relates to novel aqueous oral care compositions that can be used to combine and deliver poorly compatible ingredients, especially chlorhexidine and polyphosphates, by formulating compositions with surfactants.

[0002] Biofilms form when bacteria adhere to surfaces in some form of aqueous environment and begin secreting a sticky, gelatinous substance that can adhere to all kinds of materials—metals, plastics, soil particles, medical implants, and biological tissues. Dental plaque is a biofilm that adheres to teeth and other oral surfaces, particularly at the gingival margin, and is associated with gingivitis, periodontitis, caries, and other forms of periodontal disease. Dental plaque is cohesive and highly resistant to removal from teeth and / or oral surfaces. Bacteria associated with plaque convert sugars into glucans, insoluble polysaccharides that provide the plaque with its cohesiveness. Anaerobic bacteria in plaque metabolize sugars, producing acids that dissolve tooth minerals, thereby damaging tooth enamel and ultimately leading to caries. Saliva buffers the acids produced by bacteria and promotes the remineralization of tooth enamel, but extensive plaque can block saliva from contacting tooth enamel. The redeposition of minerals in the biofilm forms a hard deposit on the teeth called tartar (or dental plaque), which becomes a local irritant to the gums, causing gingivitis.

[0003] Various antibacterial agents can inhibit bacterial growth and thus reduce the formation of biofilms on the oral cavity surface. An important and highly effective antibacterial agent used for this purpose is the cationic biguanide reagent chlorhexidine.

[0004] Teeth consist of an inner dentin layer and an outer hard enamel layer, the latter being the protective layer of the tooth. The enamel layer is naturally opaque and white or slightly grayish-white. It is composed of hydroxyapatite mineral crystals that create a degree of porosity. These hydroxyapatite crystals form fine hexagonal rods or prisms that constitute the enamel surface. Therefore, fine spaces or pores exist between these prisms on the enamel surface. While not limiting the mechanisms, functions, or effects of this disclosure, it is believed that this porosity of enamel is the cause of discoloration by substances penetrating the enamel and causing tooth discoloration. Everyday activities, such as smoking or other oral use of tobacco products, and consuming, chewing, or drinking certain foods and beverages (especially coffee, tea, cola drinks, and red wine), can lead to undesirable staining of the tooth surface. Staining can also result from microbial activity, including microbial activity associated with dental plaque.

[0005] Since the compounds that stain teeth are usually anionic materials, cationic antibacterial agents such as chlorhexidine may cause or enhance staining by promoting chromogen deposition or by forming salts with minerals.

[0006] One approach to reducing staining and erosion, as well as biofilm formation, is to use dental floss containing mineral agents that can be used for stain removal, such as mouthwash. For example, polyphosphates exhibit significant anti-staining capabilities, and when used in oral care products, they deposit onto and protect the tooth surface, as well as complex with free calcium, thereby starving bacteria and reducing tartar buildup. However, when phosphates are combined with cationic antimicrobial agents, particularly in high-moisture formulations where the two readily interact in solution, the phosphates and cationic antimicrobial agents can complex to form insoluble precipitates, thus deactivating both components.

[0007] Therefore, while polyphosphates such as sodium tripolyphosphate can prevent tooth discoloration caused or induced by chlorhexidine, adverse interactions between these agents must be prevented to maximize the oral efficacy of the composition.

[0008] Anionic surfactants such as sodium lauryl sulfate have been suggested to help stabilize chlorhexidine and polyphosphates in aqueous solutions; however, these surfactants may irritate soft tissues, and their use is subject to regulatory restrictions. Furthermore, sodium lauryl sulfate-stabilized chlorhexidine / polyphosphate mouthwashes have been found to be prone to turbidity, possibly due to the formation of excessively large micelles.

[0009] Therefore, there is a need for novel oral compositions and methods to inhibit staining and biofilm formation, particularly those that can provide the anti-staining and anti-calculus benefits of phosphates, as well as the antibacterial and anti-biofilm benefits of chlorhexidine. Summary of the Invention

[0010] Given the high charge density and entropy-driven precipitation reactions, biguanide antimicrobial agents such as chlorhexidine often complex with anionic polyphosphates. Chlorhexidine also reacts with anionic surfactants such as sodium lauryl sulfate, and is therefore generally considered incompatible with sodium lauryl sulfate. See, for example, Barkvoll et al., “Interaction between chlorhexidine digluconate and sodium lauryl sulfate in vivo,” J Clin Periodontol. (1989) 16(9): 593-5.

[0011] The inventors have unexpectedly discovered that adding a stable amount of surfactant, such as zwitterionic, cationic, nonionic, or certain anionic surfactants, to a mouthwash composition containing chlorhexidine (e.g., chlorhexidine disodium gluconate) results in the formation of stable micelles. Without being bound by theory, it is thought that these micelles allow chlorhexidine to remain separated from polyphosphate reagents (e.g., sodium tripolyphosphate) in the mouthwash solution. Therefore, undesirable interactions between these components are suppressed, and the efficient delivery of these reagents to the teeth is enhanced.

[0012] Therefore, this disclosure provides an aqueous oral care composition comprising:

[0013] (i) An effective amount of an orally acceptable guanidine antimicrobial agent selected from biguanides (e.g., chlorhexidine, such as chlorhexidine digluconate) or poly(hexamethylene biguanide) (e.g., polyhexamethylene biguanide);

[0014] (ii) Short-chain linear polyphosphates (e.g., potassium pyrophosphate or sodium pyrophosphate or potassium tripolyphosphate or sodium tripolyphosphate); and

[0015] (iii) A stable amount of a zwitterionic, cationic or nonionic surfactant, or fatty acyl amide or fatty acyl ester carboxylate or sulfonate surfactant, or a combination thereof.

[0016] This disclosure also provides a method for inhibiting tooth erosion, staining, and / or biofilm formation, comprising applying to the oral cavity a composition as described herein.

[0017] Further applicability of the invention will become apparent from the specific embodiments provided below. It should be understood that while the detailed description and specific examples indicate preferred embodiments of the invention, they are intended for illustrative purposes only and not for limiting the scope of the invention. Detailed Implementation

[0018] The following description of preferred embodiments is merely exemplary in nature and is in no way intended to limit the invention, its application, or its uses.

[0019] The term "range" is used throughout as a concise expression to describe each value within the range. Any value within the range can be chosen as an endpoint of the range. Furthermore, all references cited herein are incorporated in full. In the event of any conflict between definitions in this disclosure and those in the cited references, this disclosure shall prevail.

[0020] Unless otherwise specified, all percentages and quantities expressed herein and elsewhere in this specification shall be understood as weight percentages. Given quantities are based on the effective weight of the material.

[0021] As is common in the art, the compositions described herein are sometimes described according to their components, although said components may dissociate, bind, or react in the formulation. For example, ions are often provided to the formulation in the form of salts that can dissolve and dissociate in aqueous solutions. It should be understood that the invention covers both mixtures of said components and products obtained therefrom.

[0022] In a first embodiment, this disclosure provides an oral care composition (composition 1) comprising:

[0023] (i) An effective amount of an orally acceptable guanidine antimicrobial agent selected from biguanides (e.g., chlorhexidine, such as chlorhexidine digluconate) or poly(hexamethylene biguanide) (e.g., polyhexamethylene biguanide);

[0024] (ii) Short-chain linear polyphosphates (e.g., potassium pyrophosphate or sodium pyrophosphate or potassium tripolyphosphate or sodium tripolyphosphate); and

[0025] (iii) A stable amount of a zwitterionic, cationic or nonionic surfactant, or fatty acyl amide or fatty acyl ester carboxylate or sulfonate surfactant, or a combination thereof.

[0026] For example, this disclosure provides an example of composition 1 as follows:

[0027] 1.1 Combination 1, wherein the biguanide is chlorhexidine.

[0028] 1.2 Combination 1.1, wherein chlorhexidine is in the form of chlorhexidine diglucuronide.

[0029] 1.3 Any of the foregoing compositions, wherein the composition comprises 0.01 to 5 wt% of a guanidine reagent, for example 0.05 to 1 wt%, 0.1 to 0.5 wt%, 0.1 to 0.3 wt%, or about 0.2 wt% of a guanidine reagent, based on the total weight of the composition.

[0030] 1.4 Any of the foregoing compositions, wherein the short-chain linear polyphosphate is a pyrophosphate or a tripolyphosphate.

[0031] 1.5 Any of the foregoing compositions, wherein the short-chain linear polyphosphate is an alkali metal or alkaline earth metal salt, such as sodium, potassium, magnesium or calcium.

[0032] 1.6 Any of the foregoing compositions, wherein the short-chain linear polyphosphate is selected from sodium tripolyphosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, or combinations thereof.

[0033] 1.7 Any of the foregoing compositions, wherein the short-chain polyphosphate is sodium tripolyphosphate.

[0034] 1.8 Any of the foregoing compositions, wherein the short-chain polyphosphate is present in an amount of 0.01 wt% to 5.0 wt%, 0.1 wt% to 5.0 wt%, 0.1 wt% to 3 wt%, 0.5 wt% to 2 wt%, or 1.0 wt% to 2 wt% or about 1.6 wt% based on the total weight of the composition.

[0035] 1.9 Any of the foregoing compositions, wherein the surfactant is an amphoteric surfactant.

[0036] 1.10 Combinations 1.9, wherein the surfactant is sulfobetaine, hydroxysulfobetaine or betaine surfactant.

[0037] 1.11 Combination 1.10, wherein the surfactant is selected from cocamidopropyl sulfonobetaine, cocamidopropyl hydroxysulfonobetaine and cocamidopropyl betaine.

[0038] 1.12 Combination 1.11, wherein the surfactant is cocamidopropyl betaine (CAPB).

[0039] 1.13 Any of the foregoing compositions, wherein the surfactant is a cationic surfactant.

[0040] 1.14 Combinations 1.13, wherein the surfactant is a quaternary ammonium salt surfactant, such as cetrimonium bromide, benzalkonium chloride and benzyl chloride.

[0041] 1.15 Combination 1.13, wherein the surfactant is quaternary pyridinium surfactant.

[0042] 1.16 Combination 1.15, wherein the surfactant is cetylpyridinium chloride (CPC).

[0043] 1.17 Combinations 1.13, wherein the surfactant is an amino acid-based cationic surfactant, such as quaternary N-(C 12-30 Acyl) amino acids (e.g., R) a -NH2 + -CH(R)-COOH, where R a It is C 12-30 Acyl chain, and R is a natural or synthetic amino acid side group) or N-fully alkylated -N'-(C 12-30 Alkyl) amino acid amides (e.g., NMe3) + -CH(R)-CONHR a , where R a It is C 12-20 Alkyl chain, and R is a natural or synthetic amino acid side group), or N-acyl amino acid alkyl ester (e.g., R...). a -NH2 +-CH(R)-COOR b , where R a It is C 12-30 An acyl chain, where R is a natural or synthetic amino acid side group, and R... b It is C 1-6 Alkyl chains (such as methyl or ethyl) and their salts.

[0044] 1.18 Combinations 1.17, wherein the amino acid-based cationic surfactant is selected from (1-hexadecylcarbamoyl-ethyl)-trimethylammonium halide, (1-hexadecylcarbamoyl-2-phenyl-ethyl)-trimethylammonium halide, 1-hexadecylcarbamoyl-1,1-dimethyl-pyrrolidineonium halide and [2-(1H-indol-3-yl)-1-hexadecylcarbamoyl-ethyl)]-trimethylammonium halide, wherein the halide is optionally a chloride, fluoride or bromide.

[0045] 1.19 Combinations 1.17, wherein the amino acid-based cationic surfactant is selected from lauroyl arginine, ethyl lauroyl arginine ester hydrochloride and sebadecyl dilauroyl amino lysine disodium.

[0046] 1.20 Any of the foregoing compositions, wherein the surfactant is a nonionic surfactant.

[0047] 1.21 Combination 1.20, wherein the surfactant is selected from fatty alcohol ethoxylates, alkylphenyl ethoxylates, fatty acid ethoxylates, ethoxylated amines or amides, polyoxyethylene / polyoxypropylene copolymers (poloxam), glycerol fatty acid esters, sorbitol fatty acid esters, alkyl polyglucosides and amine oxides.

[0048] 1.22 Combination 1.21, wherein the surfactant is an alkyl polyglucan, such as a C8-C20 glucan.

[0049] 1.23 Combination 1.22, wherein the surfactant is decyl glucoside.

[0050] 1.24 Any of the foregoing compositions, wherein the surfactant is a fatty acyl amide or a fatty acyl ester carboxylate or sulfonate, such as N-fatty acyl-N-alkyl taurine, or N-fatty acyl glycinate (e.g., N-cocoyl glycinate), or N-fatty acyl glutamate (e.g., N-cocoyl glutamate), or N-fatty acyl-N-alkyl glycinate (e.g., N-cocoyl N-methyl glycinate), or N-fatty acyl-N-alkyl glutamate (e.g., N-cocoyl N-methyl glutamate), or O-fatty acyl hydroxyethyl sulfonate (e.g., cocoyl hydroxyethyl sulfonate), or mono- or di-(C 12-20Alkyl) sulfosuccinate (e.g., dioctyl sulfosuccinate), wherein any such salt is optionally a sodium or potassium salt.

[0051] 1.25 Combination 1.24, wherein the surfactant is an N-fatty acyl-N-alkyl taurine (e.g., a sodium or potassium salt).

[0052] 1.26 Combinations 1.25, wherein the surfactant is N-cocoyl N-methyl taurate (e.g., sodium ethyl cocoyl taurate).

[0053] 1.27 Any of the foregoing compositions wherein the surfactant is present in an amount sufficient to substantially interfere with the interaction between the guanidine reagent and the short-chain linear polyphosphate, for example, in an amount sufficient to inhibit precipitate formation or reduce the efficacy of the guanidine reagent or to form micelles (e.g., containing the guanidine reagent).

[0054] 1.28 Any of the foregoing compositions, wherein the surfactant is present in amounts of 0.01 to 5.0%, 0.1 to 2.0%, 0.1 to 1.0%, 0.1 to 0.5%, 0.2 to 0.4%, 0.3 to 0.4%, 0.31% to 0.35%, 0.32 to 0.35%, 0.31% to 0.33%, 0.32 to 0.33%, 0.3 to 0.5%, 0.3 to 0.6%, 0.4 to 2%, 0.4 to 1.5%, 0.4 to 1.0%, or 0.4 to 0.5% by weight of the total composition. It is present in amounts of 8%, 0.4 to 0.6%, 0.4 to 0.5%, 0.5 to 2.0%, 0.5 to 1.5%, 0.5 to 1.0%, 0.75 to 1.5%, 0.9% to 1.3%, 0.95% to 1.2%, 0.98% to 1.1%, 1.0 to 3.0%, 1.0 to 2.0%, 1.0 to 1.5%, or about 0.32%, about 0.45%, about 0.5%, about 0.6%, about 0.75%, about 1.0%, about 1.25%, about 1.5%, or about 2.0%.

[0055] 1.29 Any of the foregoing compositions, wherein the composition comprises two or more of zwitterionic, cationic or nonionic surfactants or fatty acylamide alkyl sulfonate surfactants, for example: zwitterionic surfactants and nonionic surfactants, or cationic surfactants and nonionic surfactants, or fatty acylamide alkyl sulfonate surfactants and nonionic surfactants, or two different nonionic surfactants.

[0056] 1.30 Any of the foregoing compositions, wherein the composition further comprises a poloxamer surfactant (e.g., poloxamer 407).

[0057] 1.31 Any of the foregoing compositions, wherein the composition comprises more than 50% water by weight of the total composition.

[0058] 1.32 Any of the foregoing compositions, wherein the composition comprises 70% to 95% water, for example 70% to 90% or 70% to 80% water by weight of the total composition.

[0059] 1.33 Any of the foregoing compositions, wherein the composition comprises one or more of the following: thickeners, buffers (e.g., hydroxide bases or organic acids, such as citric acid), humectants (e.g., sorbitol, glycerin, propylene glycol), abrasives, sweeteners, flavorings, colorants, dyes, anti-caries agents (e.g., fluoride sources), antibacterial agents, whitening agents, desensitizing agents, preservatives (e.g., benzyl alcohol or benzoic acid), amino acids (e.g., lysine or arginine), or mixtures thereof.

[0060] 1.34 Composition 1.33, wherein the composition comprises a phosphate buffer.

[0061] 1.35 Composition 1.33, wherein the composition comprises a buffer selected from sodium hydroxide and potassium hydroxide.

[0062] 1.36 Composition 1.33, wherein the composition comprises a buffer selected from: lactic acid, citric acid, hydrochloric acid, glycolic acid, sodium hydroxide, potassium chloride, monosodium citrate, disodium citrate, monosodium malate, sodium carbonate, bicarbonate, sesquicarbonate, borates, silicates, monosodium phosphate, trisodium phosphate, pyrophosphate, imidazole, or combinations thereof; for example, citric acid.

[0063] 1.37 Any of the foregoing compositions, wherein the pH of the composition is about 4 to 9, about 5 to 8, about 5.5 to 7, or about 5.5 to 6.5, or about 6 to 7, or about 6 to 6.5, or about 6.05 to 6.25, or about 6.10 to 6.20, or about 6.12 to 6.19, or about 6.0 to 6.25, or about 6.0 to 6.15, or about 6.0 to 6.10.

[0064] 1.38 Any of the foregoing compositions, wherein the composition comprises a mixture of humectants comprising two or more of sorbitol, propylene glycol and glycerin.

[0065] 1.39 Any of the foregoing compositions, wherein the composition comprises a humectant, wherein the humectant is a mixture of glycerin, sorbitol and propylene glycol.

[0066] 1.40 Any of the foregoing compositions, wherein the composition comprises a moisturizer in a combined amount of 10 to 40% by weight of the composition, for example, in an amount of 20 to 40% or 30 to 40% by weight of the composition.

[0067] 1.41 Composition 1.40, wherein the composition comprises 5-10%, for example 7-10%, amounts of glycerol, sorbitol and propylene glycol, each in an amount of 5-10%, for example 7-10%.

[0068] 1.42 Any of the foregoing compositions, wherein the composition comprises a sweetener.

[0069] 1.43 Any of the foregoing compositions, wherein the composition comprises a sweetener, wherein the sweetener is sodium saccharin.

[0070] 1.44 Any of the foregoing compositions, wherein the composition comprises a flavoring agent.

[0071] 1.45 Any of the foregoing compositions, wherein the composition comprises a dye, such as FD&C Blue 1.

[0072] 1.46 Any of the foregoing compositions, wherein the composition comprises a caries antagonist.

[0073] 1.47 Any of the foregoing compositions, wherein the composition comprises a fluoride ion source.

[0074] 1.48 Any of the foregoing compositions, wherein the composition comprises a fluoride ion source, wherein the fluoride ion source is stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, fluorinated amine (e.g., N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorosulfate, or mixtures thereof.

[0075] 1.49 Any of the aforementioned compositions, wherein the composition is a mouthwash.

[0076] 1.50 Any of the foregoing compositions that is biphasic, for example, wherein the solution comprises two distinct aqueous phases with different compositions and densities.

[0077] 1.51 Any of the foregoing compositions comprising less than 5%, for example less than 2%, of a hydrophobic component.

[0078] 1.52 Any of the foregoing compositions, except for the flavoring agent, is substantially oil-free.

[0079] 1.53 Any of the foregoing compositions, wherein after storage at room temperature for three months, there is no identifiable precipitation or reaction between the short-chain polyphosphate and the orally acceptable cationic surfactant.

[0080] 1.54 Composition 1 or any one of 1.1-1.53, wherein the composition is a mouthwash comprising 0.1 to 0.5 wt% chlorhexidine (e.g., chlorhexidine disodium gluconate), 1.0 wt% to 2 wt% sodium tripolyphosphate, and 0.95% to 1.2% alkyl polyglucosides, such as C8-C20 glucosides (e.g., decyl glucosides), based on the total weight of the composition.

[0081] 1.55 Combination 1.54, wherein the pH of the composition is 5.5-7.0.

[0082] 1.56 Composition 1 or any one of 1.1-1.53, wherein the composition is a mouthwash comprising 0.1 to 0.5 wt% chlorhexidine (e.g., chlorhexidine digluconate), 1.0 wt% to 2 wt% sodium tripolyphosphate, and 0.32 to 0.35% cocamidopropyl betaine, based on the total weight of the composition.

[0083] 1.57 Combination 1.56, wherein the pH of said composition is 6.1 to 6.2 (e.g., 6.12-6.19).

[0084] 1.58 Composition 1 or any one of 1.1-1.53, wherein the composition is a mouthwash comprising 0.1 to 0.5 wt% chlorhexidine (e.g., chlorhexidine digluconate), 1.0 to 2 wt% sodium tripolyphosphate, and 0.3 to 0.6% N-cocoyl N-methyl taurate (e.g., sodium methyl cocoyl taurate) by weight of the total composition.

[0085] 1.59 Composition 1 or any one of 1.1-1.53, wherein the composition is a mouthwash comprising 0.1 to 0.5 wt% chlorhexidine (e.g., chlorhexidine digluconate), 1.0 to 2 wt% sodium tripolyphosphate, and 0.4 to 0.5% N-cocoyl N-methyl taurate (e.g., sodium methyl cocoyl taurate) by weight of the total composition.

[0086] 1.60 Composition 1 or any one of 1.1-1.53, wherein the composition is a mouthwash comprising 0.1 to 0.5 wt% chlorhexidine (e.g., chlorhexidine digluconate), 1.0 to 2 wt% sodium tripolyphosphate, and 0.5 to 1.0% hexadecylpyridinium chloride, based on the total weight of the composition.

[0087] 1.61 Combination 1.56, wherein the pH of the composition is 6.0 to 6.1.

[0088] This disclosure also provides for the use of stable amounts of zwitterionic, cationic or nonionic surfactants or fatty acylamide alkyl sulfonate surfactants or combinations thereof for stabilizing oral care formulations, such as for any of the foregoing composition 1 and the following, wherein the oral care formulation comprises a short-chain linear polyphosphate and an effective amount of an orally acceptable guanidine antimicrobial agent.

[0089] As used herein, the terms “surfactant” and “emulsifier” are equivalent when used in the art.

[0090] As used herein, "oral care composition" refers to a composition whose intended use may include oral care, oral hygiene, or oral appearance, or whose intended method of use may involve application to the oral cavity. The term "oral care composition" therefore explicitly excludes compositions that are highly toxic, have an unpleasant taste, or are otherwise unsuitable for administration to the oral cavity. In some embodiments, the oral care composition is not intended to be swallowed but is retained in the oral cavity for a sufficient period of time to achieve its intended utility. The oral care compositions disclosed herein may be used in non-human mammals such as companion animals (e.g., dogs and cats) as well as by humans. In some embodiments, the oral care compositions disclosed herein are used by humans. Oral care compositions include, for example, dental floss and mouthwash. In some embodiments, this disclosure provides mouthwash formulations.

[0091] As used in this article, "orally acceptable" means a material that is safe and palatable at relevant concentrations when used in oral care preparations such as mouthwash or dental floss.

[0092] As used herein, “orally acceptable carrier” means any carrier that can be used to formulate the oral care compositions disclosed herein. Orally acceptable carriers are harmless to mammals in the amounts disclosed herein when held in the mouth for a sufficient period to allow effective contact with tooth surfaces as required herein without swallowing. Generally, orally acceptable carriers are harmless even if accidentally swallowed. Suitable orally acceptable carriers include, for example, one or more of the following: water, thickeners, buffers, humectants, surfactants, abrasives, sweeteners, flavorings, pigments, dyes, cariogenic agents, antibacterial agents, whitening agents, desensitizing agents, vitamins, preservatives, enzymes, and mixtures thereof.

[0093] As used herein, “short-chain polyphosphates” encompasses orally acceptable monophosphates and polyphosphates, such as P… 1-6Phosphates, such as mono-, di-, or ternary orthophosphates; and dipolyphosphates, such as sodium hexametaphosphate. For example, short-chain polyphosphates may comprise alkali metal diphosphates and alkali metal pyrophosphates, such as those selected from disodium hydrogen phosphate, dipotassium hydrogen phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, and mixtures of any two or more of these. In one specific embodiment, the composition, for example, comprises a mixture of tetrasodium pyrophosphate (Na4P2O7), calcium pyrophosphate (Ca2P2O7), and disodium hydrogen phosphate (Na2HPO4). In one embodiment, tetrasodium pyrophosphate (TSPP), sodium tripolyphosphate (STPP), tetrapotassium pyrophosphate (TKPP), or mixtures thereof are used. In another embodiment, the composition comprises tetrapotassium pyrophosphate (TSPP) and sodium tripolyphosphate (STPP) (Na5P3O7). 10 A mixture of phosphates. Such phosphates are provided in amounts that effectively reduce staining on the tooth surface, enamel erosion, help clean teeth, and / or reduce plaque buildup on teeth, for example, in amounts of 0.01 wt% to 5.0 wt%, 0.1 wt% to 5.0 wt%, 0.1 wt% to 3 wt%, 0.5 wt% to 1.5 wt% or 1.0 wt% by total weight of the composition.

[0094] As used herein, "fatty acyl amide alkyl sulfonate surfactant" means a surfactant or detergent compound containing an organic hydrophobic fatty acyl group, such as C8-26 or C10-18, attached to a nitrogen atom of a tertiary amide, wherein the nitrogen atom is attached to a straight-chain C2-20 alkyl chain terminated in free or salt form with a sulfonic acid group, in order to form a water-soluble detergent. Such surfactants are employed in the form of water-soluble salts, and the salt-forming cation is typically selected from sodium, potassium, ammonium, magnesium, and mono-, di-, or tri-C2-C3 alkanolammonium, with sodium, magnesium, and ammonium cations being the most common choices. In some embodiments, the anionic surfactant is present in amounts of 0.01 to 5.0%, 0.1 to 2.0%, 0.2 to 0.4%, or about 0.33%.

[0095] As used herein, the term "fatty acid" or "fatty acyl" refers to a derivative of a natural fatty acid, such as a C4-C28 saturated or unsaturated fatty acid, and this includes its partially hydrogenated derivatives. Preferably, the fatty acid radical is a C8-C26 fatty acid or a C12-18 fatty acid, such as fatty acids derived from caprylic acid, capric acid, lauric acid, stearic acid, myristic acid, palmitic acid, hexadecenoic acid, oleic acid, linoleic acid, and linolenic acid. As used herein, "cocoyl" or "cocoate" refers to an acyl group nominally derived from coconut acid, the name for the main fatty acid mixture in coconut oil, primarily consisting of lauric acid, myristic acid, palmitic acid, capric acid, oleic acid, and caprylic acid.

[0096] As used herein, "nonionic surfactant" generally refers to a compound produced by the condensation of an oxidized alkenyl group (which is inherently hydrophilic) with an organic hydrophobic compound that can be aliphatic or alkyl aromatic compounds. Suitable examples of nonionic surfactants include poloxamer (trade name...). Sales), polyoxyethylene, polyoxyethylene dehydrated sorbitol ester (by trade name) (sales), polyethylene glycol hydrogenated castor oil (e.g., polyethylene glycol 40 hydrogenated castor oil or polyethylene glycol 60 hydrogenated castor oil), fatty alcohol ethoxylates, polyethylene oxide condensates of alkylphenols, products derived from the condensation of ethylene oxide with propylene oxide and ethylenediamine, ethylene oxide condensates of aliphatic alcohols, alkyl polyglycosides (e.g., fatty alcohol ethers of polyglycosides, such as fatty alcohol ethers of polyglucosides, such as decyl ether, lauryl ether, octyl ether, octanoyl ether, myristyl ether, stearyl ether and other ethers of glucose and polyglucoside polymers, and polyglucoside polymers, including mixed ethers, such as octyl / octanoyl (C 8-10 ) glucoside, cocoyl (C 8-16 ) glucoside and lauryl (C 12-16 (glucosides), long-chain tertiary amine oxides, long-chain tertiary phosphine oxides, long-chain dialkyl sulfoxides, and mixtures thereof.

[0097] In some embodiments, the nonionic surfactant comprises amine oxides, fatty acid amides, ethoxylated fatty alcohols, block copolymers of polyethylene glycol and polypropylene glycol, glyceryl alkyl esters, polyoxyethylene glycol octylphenol ether, sorbitol alkyl esters, polyoxyethylene glycol sorbitol alkyl esters, and mixtures thereof. Examples of amine oxides include, but are not limited to, lauroylaminopropyl dimethylamine oxide, myristoylaminopropyl dimethylamine oxide, and mixtures thereof. Examples of fatty acid amides include, but are not limited to, cocoyl monoethanolamide, laurylamide monoethanolamide, cocoyl diethanolamide, and mixtures thereof. In some embodiments, the nonionic surfactant is a combination of amine oxides and fatty acid amides. In some embodiments, the amine oxide is a mixture of lauroylaminopropyl dimethylamine oxide and myristoylaminopropyl dimethylamine oxide. In some embodiments, the nonionic surfactant is a combination of lauroyl / myristoylaminopropyl dimethylamine oxide and cocoyl monoethanolamide. In some embodiments, the nonionic surfactant is present in amounts of 0.01 to 5.0%, 0.1 to 2.0%, 0.1 to 0.6%, 0.2 to 0.4%, about 0.2%, or about 0.5%.

[0098] As used herein, the term “cationic surfactant” includes the cationic surfactants disclosed in WO 2007 / 011552A2, the contents of which are incorporated herein by reference in their entirety. Amino acid-based cationic surfactants also include those disclosed by Roy et al., Langmuir 21, 10398-10404 (2005).

[0099] As used herein, "biphase" refers to a stable liquid composition containing at least two distinct homogeneous phases having different densities, such that the phases are separated upon standing. These phases can be readily mixed by shaking, but then reseparate within a short time, such as less than half an hour. In some embodiments, the terminology does not include gels, emulsions, microemulsions, and homogeneous solutions. In some embodiments, these formulations differ from conventional biphase formulations in that both phases are aqueous, rather than one phase being hydrophobic and the other hydrophilic.

[0100] As used herein, “tartar control agent” refers to a compound or mixture of compounds that inhibits the formation of tartar (calcium phosphate mixture) on an organic matrix and / or the deposition of plaque on teeth to form tartar (calculus).

[0101] As used herein, “chemical staining” refers to discoloration of the tooth surface caused by the adsorption or absorption of a colorant on or into a surface, or by a chemical reaction between the tooth surface material (e.g., enamel) and a colorant or colorless agent in contact with the surface. In this document, “chemical staining” refers to the formation and / or development of chemical staining.

[0102] As used herein, "tooth surface" refers to the surface of a natural tooth or the hard surface of an artificial dentition, including crowns, caps, fillings, bridges, dental implants, etc. In some embodiments, the tooth surface is a natural tooth.

[0103] The composition is, for example, an oral care composition according to Composition 1 and the like, such as a mouthwash. Any composition according to Composition 1 and the like is suitable for oral care purposes, provided that the ingredients are oral acceptable.

[0104] The oral care compositions used in this disclosure contain a significant level of water. The water used in the preparation of commercially available oral compositions should be deionized and free of organic impurities. This amount of water in the composition includes the added free water plus the amount of water introduced together with other materials.

[0105] Mouthwashes typically contain significant levels of ethanol, often necessary to dissolve essential oils and prevent bacterial contamination. High levels of ethanol may be undesirable because, in addition to the possibility of ingestion abuse, ethanol may exacerbate conditions such as dry mouth. Therefore, in some embodiments, the oral care compositions of the present invention are substantially ethanol-free, for example, containing less than 1% or less than 0.1% ethanol.

[0106] Humectants can improve the viscosity, mouthfeel, and sweetness of a product, and also help preserve it from degradation or microbial contamination. Suitable humectants include edible polyols such as glycerin, sorbitol, xylitol, propylene glycol, and mixtures of other polyols and these humectants. Sorbitol is sometimes provided as a syrup of hydrogenated starch hydrolysate, which primarily contains sorbitol (if starch is completely hydrolyzed to glucose and then hydrogenated), but may also include other sugar alcohols such as mannitol, maltitol, and long-chain hydrogenated sugars due to incomplete hydrolysis and / or the presence of non-glucose sugars, and in this case, these other sugar alcohols can also be used as humectants. Therefore, sorbitol can be provided as an aqueous solution of approximately 70 wt%.

[0107] Flavoring agents used in this invention may include: extracts or oils from flavor plants such as peppermint, spearmint, cinnamon, wintergreen, and combinations thereof; cooling agents such as menthol, methyl salicylate, and commercially available products such as OptaCool from Symrise; and sweeteners, which may include polyols (which may also be used as humectants), saccharin, acesulfame potassium, aspartame, neotame, stevia, and sucralose.

[0108] A method (method A) is also provided for treating and / or inhibiting chemical staining, plaque and / or tartar on a tooth surface, comprising contacting the tooth surface with any of the aforementioned oral care compositions.

[0109] This article also provides the following method A:

[0110] A.1 Method A, wherein the composition is composition 1, for example, selected from any one of compositions 1.1-1.61.

[0111] A.2 Method A or A.1, wherein the method is used to treat chemical stains, plaque and / or tartar on the surface of teeth.

[0112] A.3 Method A.2, wherein the method is used to treat chemical stains on the surface of teeth.

[0113] A.4 Method A.2, wherein the method is used to treat plaque on the surface of teeth.

[0114] A.5 Method A.2, wherein the method is used to treat dental plaque on the surface of teeth.

[0115] A.6 Method A or A.1, wherein the method is used to inhibit chemical staining, plaque and / or tartar on the tooth surface.

[0116] A.7 Method A.6, wherein the method is used to inhibit chemical staining on the tooth surface.

[0117] A.8 Method A.6, wherein the method is used to inhibit plaque on the tooth surface.

[0118] A.9 Method A.6, wherein the method is used to inhibit plaque on the surface of teeth.

[0119] A.10 Method A or A.1-A.9, wherein the tooth surface is a human tooth.

[0120] A.11 Method A or A.1-A.10, wherein the composition comes into contact with the tooth surface by brushing.

[0121] A.12 Any of the foregoing methods A and the following, wherein the formulation is biphasic and shaken before use.

[0122] A method for treating and / or inhibiting gingival disease (method B) is also provided, comprising contacting the oral cavity with any of the aforementioned oral care compositions.

[0123] This article also provides the following method B:

[0124] B.1 Method B, wherein the composition is composition 1, such as any one of compositions 1.1-1.61.

[0125] B.2 Method B or B.1, wherein the method is used to treat gingival diseases.

[0126] B.3 Method B, B.1 or B.2, wherein the gingival disease is gingivitis.

[0127] B.4 Method B, B.1 or B, wherein the gingival disease is periodontitis.

[0128] B.5 Method B or B.1, wherein the method is used to suppress gingival disease.

[0129] B.6 Method B, B.1 or B.5, wherein the gingival disease is gingivitis.

[0130] B.7 Method B, B.1 or B.5, wherein the gingival disease is periodontitis.

[0131] Method B.8 or B.1-B.7, wherein the oral cavity is a human oral cavity.

[0132] Method B.9 or B.1-B.8, wherein the composition comes into contact with the oral cavity by brushing teeth.

[0133] B.10 Any of the foregoing methods B and the following, wherein the formulation is biphasic and shaken before use.

[0134] A method for treating and / or suppressing halitosis (method C) is also provided, comprising bringing the oral cavity into contact with any of the aforementioned oral care compositions.

[0135] This article also provides the following method C:

[0136] C.1 Method C, wherein the composition is composition 1, such as any one of compositions 1.1-1.61.

[0137] C.2 Method C or C.1, wherein the oral cavity is a human oral cavity.

[0138] C.3 Method C, C.1 or C.2, wherein the composition comes into contact with the oral cavity by brushing teeth.

[0139] C.4 Any of the foregoing methods C and the following, wherein the formulation is biphasic and shaken before use.

[0140] A method for inhibiting biofilm formation on a tooth surface (method D) is also provided, comprising contacting the tooth surface with any of the aforementioned oral care compositions.

[0141] This article also provides the following method D:

[0142] D.1 Method D, wherein the composition is composition 1, such as any one of compositions 1.1-1.61.

[0143] Method D.2 or D.1, wherein the tooth surface is a human tooth.

[0144] Method D.3, D.1, or D.2, wherein the composition comes into contact with the tooth surface by brushing.

[0145] D.4 Any of the foregoing methods D and the following, wherein the formulation is biphasic and shaken before use.

[0146] A method for treating and / or inhibiting the aggregation of bacteria and the formation of large colonies in the oral cavity is also provided (Method E), which involves contacting the oral cavity with any of the aforementioned oral care compositions.

[0147] This article also provides the following method E:

[0148] E.1 Method E, wherein the composition is composition 1, such as any one of compositions 1.1-1.61.

[0149] E.2 Method E or E.1, wherein the oral cavity is a human oral cavity.

[0150] E.3 Method E, E.1 or E.2, wherein the composition comes into contact with the oral cavity by brushing teeth.

[0151] E.4 Any of the foregoing methods E and the following, wherein the formulation is biphasic and shaken before use.

[0152] Composition 1 and the following are also provided for use in any of the methods in method AE.

[0153] As used in this article, “inhibition” refers to the reduction of staining that would otherwise form or develop after treatment. This inhibition can range from a small but observable or measurable reduction to complete inhibition of subsequent staining compared to untreated or placebo-treated tooth surfaces.

[0154] In cases where the tooth surface is essentially free of chemical staining, method A (e.g., A.1-A.12), after treatment according to the described method, will effectively inhibit the formation and development of new chemical staining that may occur, for example, due to oral use of tobacco products (including smoking) or from drinking tea, coffee, red wine, or cola. In cases where the tooth surface already has some degree of chemical staining, method A (e.g., A.1-A.12) will effectively inhibit the further development of existing staining. In some embodiments, method A (e.g., A.1-A.12) may partially or completely remove existing chemical staining and inhibit subsequent staining.

[0155] Example

[0156] Example 1 - Chlorhexidine, STPP, and nonionic surfactants

[0157] Chlorhexidine (CHX) mouthwash is very effective against gingivitis. However, after CHX is absorbed onto the tooth surface, it often causes staining after drinking coffee, tea, or red wine. This is mainly due to the electrostatic interaction between the positively charged CHX and the negatively charged stains. This means that people using chlorhexidine must avoid dark-colored foods and drinks, or get used to more yellow and stained teeth.

[0158] Sodium tripolyphosphate (STPP) exhibits significant anti-staining properties and deposits onto tooth surfaces when used in oral care products. However, when STPP is combined with CHX, the complex formed by the two can lead to the precipitation of both STPP and CHX, thereby deactivating both components.

[0159] Surprisingly, it has been found that CHX and STPP can be formulated by including the mild nonionic surfactant decyl glucoside (alkyl polyglucoside or APG) to prevent precipitation (or redissolve precipitates).

[0160] CHX micelles stabilized with APG are typically formed by preparing an aqueous solution of 0.2% CHX, adding an appropriate amount of APG, then adding 1.6% STPP and an appropriate amount of citric acid to bring the solution pH to the range of 5.5-7. Preferably, the APG surfactant is added before the CHX and STPP are combined. This is because CHX and STPP form an insoluble complex when combined in aqueous solution. If APG is added after this complex has formed, an insoluble aggregate layer may form in some cases.

[0161] For the following experiments, 0.2 wt% aqueous solutions of chlorhexidine gluconate and 10.0 wt% aqueous solutions of decyl glucoside (“APG”) were prepared. The pH of the decyl glucoside solution was adjusted to 5.5–7.0 using citric acid. Seven formulations were prepared as shown in Table 1. For each formulation, an appropriate amount of decyl glucoside solution was added to an appropriate amount of chlorhexidine stock solution. STPP was then added to each formulation, and the mixture was stirred using a bath sonicator until no large solid residue remained. Additional citric acid was added to adjust the pH to 5.5–7.0. The formulations were then stirred for another five minutes, allowed to equilibrate for 30 minutes, and then observed and the transmittance was measured.

[0162] Table 1:

[0163] preparation CHX (wt%) APG (wt%) STPP (wt%) pH Light transmittance (%) Visual 1-1 0.20％ 0.75％ 1.60％ 6.39 21 Opaque solution 1-2 0.20％ 0.82％ 1.60％ 6.76 21 Opaque solution 1-3 0.20％ 0.85％ 1.60％ 6.59 25 Opaque solution 1-4 0.20％ 0.92％ 1.60％ 6.31 85 Opaque solution 1-5 0.20％ 0.98％ 1.60％ 6.33 99 Clear solution 1-6 0.20％ 1.00％ 1.60％ 6.76 92 Clear solution 1-7 0.20％ 1.10％ 1.60％ 5.96 99 Clear solution

[0164] The transmittance of the DI water was calibrated to 100 prior to the measurements. Results showed that the mixture was a milky white suspension when the APG was equal to or below 0.92%. When the APG was above 0.92%, the mixture was a stable, clear solution.

[0165] The antimicrobial activity of the formulation was tested to determine whether chlorhexidine was fully active. The Alamar blue test for antimicrobial activity was performed according to standard methods. Bacterial inoculum was prepared by diluting fresh saliva twice with deionized water, centrifuging at 8000 G / 25 °C for 10 minutes, and then pouring the clear supernatant into a glass jar. The negative control (A) was distilled water. The positive control (B) was a 2 wt% chlorhexidine gluconate solution. The APG control (C) was a 10 wt% decyl glucoside solution. Two test solutions were prepared: (D) 2 wt% chlorhexidine gluconate and 10 wt% decyl glucoside; and (E) 2 wt% chlorhexidine gluconate and 10 wt% decyl glucoside solution, with 14% w / w STPP added. Each test solution was combined with saliva at a weight ratio of 1:10 (solution to saliva). The pH of each mixture was adjusted to 5.5–7 by adding citric acid. The mixture was vortexed for 1 minute and incubated at 37°C for 30 minutes. The subsequent addition of 200 μL of Alma Blue dye immediately produced a blue color in all samples. Photographs were taken at different time intervals (0 h, 24 h, 48 h) for comparison to show the evolution of the color development. Blue indicates that bacteria in the saliva were killed and no bacterial growth occurred, while pink indicates that live bacteria were still present. Colors in between, such as purple, indicate that bacteria have begun to regrow. The results are shown in the table below:

[0166]

[0167] The results showed that the negative control remained a clear pink after overnight incubation. The APG negative control showed a color change from blue to pink after two days. Both the APG-CHX mixture and the APG-CHX-STPP mixture showed approximately the same level of antimicrobial activity as the CHX positive control.

[0168] These results demonstrate that APG alone can stabilize CHX and STPP in aqueous systems and maintain solution clarity at concentrations greater than 0.99%, thereby preventing interactions between cationic CHX and anionic STPP. At a concentration of 0.2%, APG-stabilized CHX remains effective against bacteria regardless of the presence of STPP. Therefore, APG can be used in mouthwash products to stabilize CHX, which provides antibacterial properties, and, together with STPP, offer anti-staining benefits. Consequently, the formulation is mild, without the harshness and irritation that may be present with other surfactants.

[0169] Example 2 - Chlorhexidine, STPP and zwitterionic surfactants

[0170] It has been surprisingly discovered that CHX and STPP can be formulated by including the mild zwitterionic surfactant cocamidopropyl betaine (CAPB) to prevent precipitation (or redissolve the precipitate).

[0171] CHX micelles stabilized with CAPB are typically formed by preparing an aqueous solution of 0.2% CHX and 1.6% STPP, adding appropriate amounts of CAPB and citric acid to bring the solution pH to the range of 6.12–6.19. Surprisingly, it was found that, starting from an initial pH of 9, the mixture changed from a milky white suspension to a clear solution as the pH decreased to 6.2.

[0172] For the following experiments, 0.2 wt% chlorhexidine gluconate aqueous solution and 2.0 wt% CAPB aqueous solution were prepared. STPP was added to the chlorhexidine solution to provide 1.6 wt% STPP. Five formulations were prepared as shown in Table 2. For each formulation, an appropriate amount of CAPB solution was added to an appropriate amount of chlorhexidine / STPP stock solution. The mixture was stirred using a bath sonicator, and then additional citric acid was added to adjust the pH to 6.12–6.19. The formulations were then stirred for another five minutes and allowed to equilibrate for 18 hours before observation. It should be noted that solutions 2-2 and 2-3 were clear at the time of preparation but gradually formed precipitates over several hours. In each case where precipitates formed, the precipitates had completely settled to the bottom of the test bottle by the time of observation. In the second round of experiments, two formulations with 0.33% CAPB were compared, one with pH adjusted to 6.19 and the other unadjusted (pH 9.1). The unadjusted solution was very opaque, but there was no visible precipitate solid, and this remained the case after 18 hours.

[0173] Table 2:

[0174]

[0175] The results showed that when CAPB was below 0.32%, the mixture formed a precipitate upon standing, while when CAPB was equal to or above 0.32%, the mixture was a stable, clear solution if prepared at a pH less than 7, for example, 6.12 to 6.19.

[0176] The antimicrobial activity of the formulation was tested using the Almar Blue test as described in Example 1. The negative control (A) was distilled water. The positive control (B) was a 2 wt% chlorhexidine gluconate solution. The CAPB control (C) was a 3.3 wt% CAPB solution. Two test solutions were prepared: (D) 2 wt% chlorhexidine gluconate and 3.3 wt% CAPB; and (E) 2 wt% chlorhexidine gluconate and 3.3 wt% CAPB solution with 14 wt% STPP added. Each test solution was combined with saliva at a weight ratio of 1:10 (solution to saliva). The pH of each mixture was adjusted to 5.5–7 by adding citric acid. The mixtures were vortexed for 1 minute and incubated at 37°C for 30 minutes. The subsequent addition of 200 μL of Almar Blue dye immediately produced a blue color in all samples, and photographs were taken at different time intervals (0 h, 24 h, 48 h) for comparison to show the evolution of color development. Blue indicates that bacteria in saliva have been killed and no bacterial growth has occurred, while pink indicates that live bacteria are still present. Colors in between, such as purple, indicate that bacteria have begun to regrow. The results are shown in the table below:

[0177]

[0178] The results showed that the negative control remained a clear pink after overnight incubation. The CAPB negative control showed a color change from blue to pink after two days. Both the CAPB-CHX mixture and the CAPB-CHX-STPP mixture showed approximately the same level of antimicrobial activity as the CHX positive control.

[0179] These results demonstrate that CAPB alone can stabilize CHX and STPP in aqueous systems and maintain solution clarity at concentrations greater than 0.31% and pH ranges of 6.1 to 6.2, thereby preventing interactions between cationic CHX and anionic STPP. At a concentration of 0.2%, CAPB-stabilized CHX remains effective against bacteria regardless of the presence of STPP. Therefore, CAPB can be used in mouthwash products to stabilize CHX, which provides antibacterial properties, and to provide anti-staining benefits in conjunction with STPP. Consequently, the formulation is mild, without the abrasive and irritating effects that other surfactants may exhibit.

[0180] Example 3: Chlorhexidine, STPP, and sodium methyl cocoyl taurate surfactants

[0181] It has been previously shown that the anionic surfactant sodium lauryl sulfate (SLS) can stabilize CHX-STPP mouthwash formulations by forming micelles. However, such solutions have also been found to be not clear and transparent, but rather slightly opaque. The opacity of the solution becomes more pronounced under colder conditions. Without being bound by theory, it is assumed that these clarity issues are due to the relatively large size of the micelles formed between CHX and SLS.

[0182] Surprisingly, the mild anionic surfactant sodium methyl cocoyl taurate (“taurate”) has been found to stabilize CHX in solution and improve clarity.

[0183] Two mouthwash solutions were prepared according to Table 3 below, one using SLS as a stabilizer and the other using taurine.

[0184] Table 3: Test Preparations

[0185] Material Formulation 3-1 (wt%) Formulation 3-2 (wt%) Chlorhexidine digluconate (19% w / v solution) 1.0 1.0 Poloxamer 407 (nonionic surfactant) 0.33 0.33 Sodium tripolyphosphate 1.66 1.66 Sodium lauryl sulfate 0.45 - Taurine - 0.45 glycerin 7.2 7.2 Sorbitol (70% solution) 9.6 (6.7 activity) 9.6 (6.7 activity) Propylene glycol 7.0 7.0 Flavorings / Sweeteners 0.17 0.17 Colorant 0.0001 0.0001 Citric acid 0.37 0.37 preservative 0.25 0.25 water Approximately 72g (appropriate amount) Appropriate amount (approximately 72g)

[0186] Formulation 3-2 was found to be clear and colorless, while formulation 3-1 was noticeably opaque.

[0187] To assess the freeze-thaw stability of the solutions, each solution was frozen at -30°C for three 24-hour cycles and then thawed to room temperature for 24 hours. Formulation 3-2 remained clear and colorless after three freeze-thaw cycles, but formulation 3-1 was completely opaque (more opaque than initially).

[0188] To further evaluate the effect of taurine concentration, additional formulations 3-3, 3-4, 3-5, 3-6, and 3-7 were prepared, each containing 0.1 wt% taurine, 0.2 wt% taurine, 0.25 wt% taurine, 0.35 wt% taurine, or 0.45 wt% taurine, respectively (the remainder being water). Therefore, formulation 3-7 was identical to formulation 3-2, but was prepared in parallel with formulations 3-3 through 3-6 by adding taurine to the originally complete mouthwash formulation.

[0189] preparation CHX (wt%) Taurine (wt%) STPP (wt%) Light transmittance (%) Visual 3-3 0.2％ 0.1％ 1.66％ 18 Extremely opaque solution 3-4 0.2％ 0.2％ 1.66％ 18 Extremely opaque solution 3-5 0.2％ 0.25％ 1.66％ 65 Slightly opaque solution 3-6 0.2％ 0.35％ 1.66％ 90 Clear solution 3-7 0.2％ 0.45％ 1.66％ 95 Clear solution

[0190] The 0.1% taurine solution was found to be very opaque, with a large amount of visible white precipitate settling to the bottom. Compared to the 0.1% taurine solution, the 0.2% and 0.25% taurine solutions were less opaque and had less white precipitate. The 0.35% taurine solution was slightly opaque but had no precipitated solids. Only the 0.45% taurine solution was clear and colorless, with no precipitated solids. These observations are consistent with the transmittance results.

[0191] The content of 0.45% taurine preparation 3-2 was determined by content assay to ascertain the amount of free CHX present. The amount of free CHX was found to be 0.18 wt%, only slightly lower than the calculated theoretical value of 0.19%.

[0192] Example 4 - Chlorhexidine, STPP and cationic surfactants

[0193] It has been surprisingly discovered that CHX and STPP can be formulated by including the mild cationic surfactant hexadecylpyridinium chloride (CPC) to prevent precipitation (or redissolve precipitates).

[0194] For the following experiments, a 0.2 wt% aqueous solution of chlorhexidine gluconate was prepared according to Table 4 below, but with “pores” of 1.6% STPP and 0–1.0% surfactant / water. Five formulations were prepared, differing only in the amounts of water and CPC surfactant. For each formulation, an appropriate amount of CPC and / or water was added to the initial stock solution, followed by stirring for 30 minutes. STPP was then added, followed by stirring for another 30 minutes. Citric acid (0.20 g) was then added to adjust the pH to 6–6.10.

[0195] Table 4:

[0196] preparation CHX (wt%) CPC (wt%) STPP (wt%) pH Visual 4-1 0.20％ 0.00％ 1.60％ 6.08 A clear solution containing a large amount of precipitated solids 4-2 0.20％ 0.25％ 1.60％ 6.05 Extremely opaque solution, no solids 4-3 0.20％ 0.50％ 1.60％ 6.03 Clear colorless solution 4-4 0.20％ 0.75％ 1.60％ 6.07 Clear colorless solution 4-5 0.20％ 1.00％ 1.60％ 6.01 Clear colorless solution

[0197] Precipitation occurred in all samples upon the addition of STPP. Notably, the precipitate in the control samples (i.e., without CPC) exhibited a solid white appearance with distinct particles, while the samples containing CPC appeared as turbid solutions (except for the 0.25% CPC sample, where some solid white particles were observed). The initial pH of each solution was 9.50 to 9.56 prior to pH adjustment. After subsequent pH adjustment to 6.00 ± 0.10, samples containing 0.50–1.00% CPC dissolved and remained clear solutions (Figure 1). Without being bound by theory, it is assumed that the initial precipitation in the samples containing 0.50–1.00% CPC occurred due to the pH increase and the formation of water-insoluble neutral CHX. However, in the control, it is assumed that an insoluble complex formed between CHX and STPP that would not dissolve upon acidification. Other cationic surfactants (e.g., benzalkonium chloride) were also evaluated, but no stabilizing effect was observed with these other cationic surfactants.

Claims

1. An oral care composition comprising (i) 0.1 to 0.5 wt% of chlorhexidine; (ii) 0.5 wt% to 2 wt% of sodium tripolyphosphate; as well as (iii) Surfactants and pH selected from the following: (a) 0.32 to 0.33 wt% cocamidopropyl betaine (CAPB) and pH 6.1 to 6.2; (b) 0.5 to 1.0 wt% cetylpyridinium chloride (CPC) and a pH of 6.0 to 6.1; (c) 0.98 to 1.1 wt% alkyl polyglucoside (APG) and pH 5.5 to 7.0; or (d) 0.3 to 0.5 wt% sodium methyl cocoyl taurate and a pH of 5.0 to 8.0, All weight percentages are based on the total weight of the oral care composition.

2. The composition according to claim 1, wherein the chlorhexidine is in the form of chlorhexidine diglucuronide.

3. The composition of claim 1, wherein the composition comprises 0.1 to 0.3 wt% chlorhexidine based on the total weight of the composition.

4. The composition according to claim 1, wherein the composition further comprises tetrasodium pyrophosphate, tetrapotassium pyrophosphate, or a combination thereof.

5. The composition according to claim 1, wherein the sodium tripolyphosphate is present in an amount of 1.0 wt% to 2 wt% based on the total weight of the composition.

6. The composition according to claim 1, wherein the chlorhexidine is present in an amount of 0.2 wt% based on the total weight of the composition.

7. The composition according to claim 1, wherein the sodium tripolyphosphate is present in an amount of 1.6 wt% based on the total weight of the composition.

8. The composition of claim 1, wherein the composition comprises 0.1 to 0.3 wt% chlorhexidine and 1.0 wt% to 2 wt% sodium tripolyphosphate based on the total weight of the composition.

9. The composition of claim 1, wherein the composition comprises 0.2 wt% chlorhexidine and 1.6 wt% sodium tripolyphosphate based on the total weight of the composition.

10. The composition according to claim 1, wherein the surfactant is 0.32 to 0.33 wt% cocamidopropyl betaine and the pH is 6.1 to 6.

2.

11. The composition according to claim 1, wherein the surfactant is 0.98 to 1.1 wt% of an alkyl polyglucan and has a pH of 5.5 to 7.

0.

12. The composition according to claim 11, wherein the surfactant is decyl glucoside.

13. The composition according to claim 1, wherein the surfactant is 0.3 to 0.5 wt% sodium methylcocoyl taurate and the pH is 5.0 to 8.

0.

14. The composition of claim 1, wherein the surfactant is 0.5 to 1.0 wt% hexadecylpyridinium chloride and the pH is 6.0 to 6.

1.

15. The composition of claim 1, wherein the composition comprises 70% to 95% water by weight of the total weight of the composition.

16. The composition of claim 1, wherein the composition comprises one or more of the following: thickener, buffer, humectant, abrasive, sweetener, flavoring agent, colorant, dye, anti-caries agent, antibacterial agent, whitening agent, desensitizing agent, preservative, amino acid, or mixture thereof.

17. The composition according to any one of claims 1 to 16, wherein the composition is a mouthwash.

18. Use of the composition according to any one of claims 1 to 16 for manufacturing a dental cleaning agent or mouthwash, said dental cleaning agent or mouthwash for use in... a) Treating and / or inhibiting chemical staining, plaque, and / or tartar on the tooth surface. b) Treat and / or suppress gum disease c) Treat and / or suppress halitosis d) Inhibit biofilm formation on the tooth surface, and / or e) Treat and / or inhibit bacterial aggregation and growth in the oral cavity.

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