Micellar mouthwash composition

Abstract

The present disclosure relates to mouthwash compositions comprising a fluorinated amine, or an amine base, and a fluoride, and an alkyl glucoside, and related methods of use of the compositions.

Description

Technical Field

[0001] The present disclosure relates to micellar mouthwash compositions comprising a fluorinated amine and an alkyl glucoside, and related methods of using said compositions. Background Art

[0002] Fluoride is one of the agents commonly used to combat dental caries. Fluoride greatly contributes to dental health by strengthening tooth enamel to make it more resistant to tooth decay. Fluoride also helps remineralize weakened tooth enamel and reverse early signs of tooth decay. Many oral care products such as toothpaste, mouthwash, and professional dental treatment products contain fluoride. Fluorinated amines are well-known fluoride ion sources used in oral care products. The amine base has a hydrophobic non-polar tail and a hydrophilic polar amine head. Thus, the fluorinated amine acts like a surfactant. Due to its surface activity, when using a hygiene composition orally, the fluorinated amine forms a thin hydrophobic film on the tooth enamel. Thus, on the one hand, the tooth enamel becomes more resistant to acid erosion due to the formation of a CaF2 coating layer. On the other hand, the long-chain hydrocarbon residues form a hydrophobic layer that prevents the formation of deposits and the erosion of tooth enamel by acid degradation products.

[0003] Micelles are aggregates of surfactants dispersed in a liquid, thus forming a colloidal suspension. Micelles provide dual benefits in products. Micelles deliver lipophilic active substances such as essential oils and also act to improve cleaning efficiency by encapsulating dirt.

[0004] There is a need for mouthwash formulations containing fluorinated amines with improved micellar properties. Summary of the Invention

[0005] In one aspect, the present invention provides a mouthwash composition comprising a fluorinated amine, or an amine base and a fluoride, and an alkyl glucoside. In certain embodiments, the fluorinated amine is oraphyll (N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride).

[0006] In some embodiments, the fluorinated amine is present in an amount of 0.5% to 1.5% by weight of the composition, such as 0.5% to 1.2%, 0.5% to 1%, 0.7% to 1.5%, 0.7% to 1.2%, 0.7% to 1%, 0.8% to 1.5%, 0.8% to 1.2%, 0.8% to 1%, 0.85% to 0.95%, or about 0.9%.

[0007] The alkyl glucoside may be C 8-25 alkyl glucoside, such as C 8-18 alkyl glucoside or C 10-18Alkyl glucoside. In some embodiments, the alkyl glucoside is selected from cocoyl glucoside, decyl glucoside, capryloyl / capryl glucoside, lauryl glucoside, cocoyl glucoside, octyl glucoside, cetearyl glucoside, cetyl glucoside, hexadecyl glucoside, arachidyl glucoside, and combinations thereof. In some embodiments, the alkyl glucoside is selected from cocoyl glucoside, decyl glucoside, capryloyl / capryl glucoside, and combinations thereof. In certain embodiments, the alkyl glucoside is cocoyl glucoside.

[0008] In some embodiments, the alkyl glucoside is present in an amount of 0.1% to 2.5% by weight of the composition, such as 0.1% to 1%, 0.1% to 0.6%, 0.1% to 0.5%, 0.1% to 0.4%, 0.1% to 0.3%, 0.2% to 0.4%, 0.2% to 0.3%, 0.25% to 0.3%, or about 0.27%.

[0009] In another aspect, the present invention provides a method comprising applying to the oral cavity of a subject in need thereof an effective amount of any one of the mouthwash compositions disclosed herein to: (i) reduce or inhibit the formation of dental caries, (ii) alleviate, repair or inhibit pre-carious lesions of tooth enamel, (iii) alleviate or inhibit tooth demineralization and promote tooth remineralization, (iv) alleviate tooth hypersensitivity, (v) alleviate or inhibit gingivitis, (vi) promote the healing of ulcers or wounds in the oral cavity, (vii) reduce the level of acid-producing bacteria, (viii) reduce or inhibit the formation of microbial biofilms in the oral cavity, (ix) reduce or inhibit the formation of plaque in the oral cavity, (x) promote general health, or (xi) clean teeth and the oral cavity.

[0010] In another aspect, the present invention provides the use of an alkyl glucoside in any one of the mouthwash compositions comprising a fluorinated amine, such as the mouthwash compositions disclosed herein, for improving the micellar properties of the mouthwash composition, such as reducing the critical micelle concentration (CMC) of the fluorinated amine in the composition and / or reducing the micelle (colloidal particle) size.

[0011] Other applicable fields of the present disclosure will become apparent from the detailed description provided below. It should be understood that the detailed description and specific examples, while indicating some exemplary aspects of the present disclosure, are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 The 2D NOESY spectra of formulation A (top) and formulation B (bottom) are depicted.

[0013] Figure 2 Depicts LC-HRMS data (indicated by arrows) showing an amine base-coco glucoside complex.

[0014] Figure 3 Depicts LC-HRMS data (indicated by arrows) showing an amine base-coco glucoside complex. Detailed Description

[0015] The following description of various exemplary aspects is merely exemplary in nature and is in no way intended to limit the present disclosure, its application, or uses.

[0016] As used throughout, ranges are used as shorthand for describing each and every value within the range. Any value within the range can be selected as the endpoint of the range.

[0017] Unless otherwise indicated, all percentages and amounts expressed herein and elsewhere in the specification are to be understood as referring to weight percentages. The amounts given are based on the active weight of the materials.

[0018] In the present invention, it has been found that the use of alkyl glucosides as surfactants improves the micellar properties of mouthwash formulations containing fluorinated amines (such as oraphene (N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride)). Compared with fluorinated amine / PEG-40 hydrogenated castor oil, the combination of fluorinated amine and coco glucoside is found to reduce the critical micelle concentration (CMC) of the fluorinated amine and to decrease the micelle (colloidal particle) size. The low critical micelle concentration of the fluorinated amine / coco glucoside mixture ensures a greater number of micelles in the mouthwash. The smaller micelle size of the fluorinated amine / coco glucoside complex exhibits higher mobility, which may enhance the active substance delivery and antibacterial efficacy of the mouthwash. 2D NOESY and dynamic light scattering data indicate strong interactions between the fluorinated amine and coco glucoside. Without being bound by any theory, the improved micellar properties may be due to strong synergistic interactions between the cationic surfactant and the nonionic surfactant with comparable molecular sizes. Thus, for micelle formation in mouthwash formulations, the combination of fluorinated amine / coco glucoside is an improved alternative to fluorinated amine / PEG-40 hydrogenated castor oil.

[0019] In one aspect, the present invention provides a mouthwash composition (Composition 1.0) comprising a fluorinated amine, or an amine base and a fluoride, and an alkyl glucoside.

[0020] For example, the present invention includes:

[0021] 1.1. Composition 1.0, wherein the alkyl glucoside is C 8-25 alkyl glucoside, such as C 8-18 alkyl glucoside, or C10-18 Alkyl glucoside.

[0022] 1.2. Any one of the foregoing compositions, wherein the alkyl glucoside is selected from cocoyl glucoside, decyl glucoside, capryloyl / capryl glucoside, lauryl glucoside, octyl glucoside, cetearyl glucoside, cetyl glucoside, hexadecyl glucoside, arachidyl glucoside, and combinations thereof.

[0023] 1.3. Any one of the foregoing compositions, wherein the alkyl glucoside is selected from cocoyl glucoside, decyl glucoside, capryloyl / capryl glucoside, and combinations thereof.

[0024] 1.4. Any one of the foregoing compositions, wherein the alkyl glucoside is cocoyl glucoside. 1.5. Any one of the foregoing compositions, wherein the alkyl glucoside is present in an amount of 0.1% to 2.5% by weight of the composition, such as 0.1% to 1%, 0.1% to 0.6%, 0.1% to 0.5%,

[0025] 0.1% to 0.4%, 0.1% to 0.3%, 0.2% to 0.4%, 0.2% to 0.3%, 0.25% to 0.3%, or about 0.27%.

[0026] 1.6. Any one of the foregoing compositions, wherein the amine base is a primary amine, a secondary amine, a tertiary amine, or a combination thereof.

[0027] 1.7. Any one of the foregoing compositions, wherein the amine base comprises a primary amine base or consists of a primary amine base.

[0028] 1.8. Any one of the foregoing compositions, wherein the amine base comprises a secondary amine base or consists of a secondary amine base.

[0029] 1.9. Any one of the foregoing compositions, wherein the amine base comprises a tertiary amine base or consists of a tertiary amine base.

[0030] 1.10. Any one of the foregoing compositions, wherein the amine base is of plant origin.

[0031] 1.11. Any one of the foregoing compositions, wherein the amine base is of animal origin.

[0032] 1.12. Any one of the foregoing compositions, wherein the amine base is derived from tallow.

[0033] 1.13. Any one of the foregoing compositions, wherein the amine base is derived from rapeseed oil or from rice bran oil.

[0034] 1.14. Any one of the foregoing compositions, wherein the amine base is a linear or branched aliphatic amine or polyamine, or a mixture thereof.

[0035] 1.15. The foregoing composition, wherein the amine base is a saturated or unsaturated C 12-20 alkylamine base or a saturated or unsaturated C 12-20 alkyl polyamine base, or a mixture thereof.

[0036] 1.16. Any of the foregoing compositions, wherein the amine base is myristyl, palmityl, linoleyl, oleyl or stearyl amine or polyamine, or a combination thereof.

[0037] 1.17. Any of the foregoing compositions, wherein the amine base is a polyamine (e.g., a monoamine base, a diamine base and / or a triamine base).

[0038] 1.18. Any of the foregoing compositions, wherein the amine base is a monoamine base.

[0039] 1.19. Any of the foregoing compositions, wherein the amine base is a diamine base.

[0040] 1.20. Any of the foregoing compositions, wherein the amine base is a triamine base.

[0041] 1.21. Any of the foregoing compositions, wherein the amine base comprises one or more of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol), and / or oleyl diamine ethoxylate, and / or N-octadec-9-enamine, and / or alkyl trihydroxyethyl propanediamine.

[0042] 1.22. Any of the foregoing compositions, wherein the amine base is N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol).

[0043] 1.23. Any of the foregoing compositions, wherein the amine base is N-octadec-9-enamine.

[0044] 1.24. Any of the foregoing compositions, wherein the amine base and the fluoride form a fluorinated amine in situ.

[0045] 1.25. Any of the foregoing compositions, wherein the fluorinated amine is orapin (N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride).

[0046] 1.26. Any of the foregoing compositions, wherein the fluorinated amine is present in an amount of 0.5% to 1.5% by weight of the composition, such as 0.5% to 1.2%, 0.5% to 1%, 0.7% to 1.5%, 0.7% to 1.2%, 0.7% to 1%, 0.8% to 1.5%, 0.8% to 1.2%, 0.8% to 1%, 0.85% to 0.95%, or about 0.9%.

[0047] 1.27. Any one of the foregoing compositions, wherein the composition comprises oraftor and cocoyl glucoside.

[0048] 1.28. Any one of the foregoing compositions, wherein the composition comprises oraftor in an amount of 0.5% to 1.5% by weight of the composition and cocoyl glucoside in an amount of 0.1% to 1% by weight of the composition.

[0049] 1.29. Any one of the foregoing compositions, wherein the composition comprises oraftor in an amount of 0.8% to 1.2% by weight of the composition and cocoyl glucoside in an amount of 0.2% to 0.4% by weight of the composition.

[0050] 1.30. Any one of the foregoing compositions, wherein the composition comprises oraftor in an amount of 0.8% to 1%, such as about 0.9%, by weight of the composition and cocoyl glucoside in an amount of 0.25% to 0.3%, such as about 0.27%, by weight of the composition.

[0051] 1.31. Any one of the foregoing compositions, wherein the composition does not contain or substantially does not contain sodium lauryl sulfate.

[0052] 1.32. Any one of the foregoing compositions, wherein the composition does not contain or substantially does not contain alkyl sulfates.

[0053] 1.33. Any one of the foregoing compositions, wherein the composition does not contain or substantially does not contain anionic surfactants.

[0054] 1.34. Any one of the foregoing compositions, wherein the composition does not contain any surfactants other than alkyl glucosides and fluorinated amines.

[0055] 1.35. Any one of the foregoing compositions, comprising a humectant, such as selected from glycerol, sorbitol, propylene glycol, polyethylene glycol, xylitol, and mixtures thereof.

[0056] 1.36. Any one of the foregoing compositions, wherein the composition comprises one or more soluble phosphates, such as selected from tetrasodium pyrophosphate (TSPP), sodium tripolyphosphate (STPP), and combinations thereof.

[0057] 1.37. Any one of the foregoing compositions, wherein the composition comprises a basic amino acid in free form or salt form, optionally wherein the basic amino acid includes arginine.

[0058] 1.38. Any one of the foregoing compositions, wherein the composition comprises a zinc ion source.

[0059] 1.39. Composition 1.38, wherein the zinc ion source is selected from zinc oxide, zinc sulfate, zinc chloride, zinc citrate, zinc lactate, zinc gluconate, zinc malate, zinc tartrate, zinc carbonate, zinc phosphate, and combinations thereof.

[0060] 1.40. Any one of Compositions 1.38 to 1.39, wherein the zinc ion source is selected from zinc oxide, zinc citrate, and combinations thereof, optionally wherein the zinc ion source is a combination of zinc oxide and zinc citrate.

[0061] 1.41. Any one of the foregoing compositions, comprising a sweetening agent, optionally wherein the sweetening agent is saccharin.

[0062] 1.42. Any one of the foregoing compositions, comprising a breath freshener.

[0063] 1.43. Any one of the foregoing compositions, comprising an aromatic agent.

[0064] 1.44. Any one of the foregoing compositions, comprising a flavoring agent.

[0065] 1.45. Any one of the foregoing compositions, comprising a pigment.

[0066] 1.46. Any one of the foregoing compositions, comprising a preservative.

[0067] 1.47. Any one of the foregoing compositions, wherein the composition comprises water.

[0068] 1.48. Any one of the foregoing compositions, which is substantially free of ethanol, for example, having less than 0.5% by weight of ethanol.

[0069] 1.49. Any one of the foregoing compositions, wherein the mouthwash is a micellar mouthwash.

[0070] The mouthwash composition of the present invention comprises an amine fluoride, or an amine base and a fluoride. As used herein, the term "amine base" may refer to a primary amine base, a secondary amine base or a tertiary amine base. A "primary amine base" refers to a compound containing at least one amine in which the nitrogen atom is directly bonded to one carbon of any hybridization (excluding a carbonyl carbon). A "secondary amine base" refers to a compound containing at least one amine in which the nitrogen atom is directly bonded to two carbons of any hybridization (excluding a carbonyl carbon). A "tertiary amine base" refers to a compound containing at least one amine in which the nitrogen atom is directly bonded to three carbons of any hybridization (excluding a carbonyl carbon). "Amine base" may be used to refer to a compound containing a plurality of primary amine groups, secondary amine groups and / or tertiary amine groups (e.g., tertiary polyamines). In particular, the term "amine base" does not include acid addition salts (e.g., hydrochloride and hydrofluoride salts), and thus refers to the free base form of the molecule. In some embodiments, the amine base is selected from N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol), oleyl diamine ethoxylate, N-octadec-9-enamine, alkyl trihydroxyethylpropylenediamine, and combinations thereof. The hydrofluoride derivative of an amine is referred to herein as "amine fluoride". In a method for producing or manufacturing a composition containing an amine fluoride, the amine base may be a precursor for forming the amine fluoride. In certain embodiments, the amine fluoride is orafluor (N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride).

[0071] In some embodiments, the amine base and the fluoride form an amine fluoride in situ. As used herein, the term "in situ" is used to refer to the formation of a chemical product (e.g., an amine fluoride) in the mouthwash composition. For example, the reaction may be a salt-forming reaction carried out by mixing an amine with a fluoride source and an acid, thereby producing an amine fluoride and a salt.

[0072] In some embodiments, the amine fluoride is present in an amount of 0.5% to 1.5% by weight of the composition, such as 0.5% to 1.2%, 0.5% to 1%, 0.7% to 1.5%, 0.7% to 1.2%, 0.7% to 1%, 0.8% to 1.5%, 0.8% to 1.2%, 0.8% to 1%, 0.85% to 0.95%, or about 0.9%.

[0073] The mouthwash composition of the present invention comprises an alkyl glucoside. An alkyl glucoside is a compound produced by combining a sugar, such as glucose, with a fatty alcohol. Alkyl refers to a non-branched or branched carbon chain. In some embodiments, the alkyl is non-branched. The alkyl may be saturated or unsaturated. In some embodiments, the alkyl is saturated. For example, the structure of decyl glucoside is shown below:

[0074]

[0075] The alkyl glucoside may be C 8-25 alkyl glucoside, such as C8-18 Alkyl glucoside, C 10-18 alkyl glucoside or C 10-16 alkyl glucoside. In some embodiments, the alkyl glucoside is selected from cocoyl glucoside, decyl glucoside, octanoyl / octyl glucoside, lauryl glucoside, octyl glucoside, cetearyl glucoside, cetyl glucoside, hexadecyl glucoside, arachidyl glucoside, and combinations thereof. In certain embodiments, the alkyl glucoside is cocoyl glucoside.

[0076] In some embodiments, the alkyl glucoside is present in an amount of 0.1% to 2.5% by weight of the composition, such as 0.1% to 1%, 0.1% to 0.6%, 0.1% to 0.5%, 0.1% to 0.4%, 0.1% to 0.3%, 0.2% to 0.4%, 0.2% to 0.3%, 0.25% to 0.3%, or about 0.27%.

[0077] In some embodiments, the mouthwash composition of the present invention does not contain or substantially does not contain sodium lauryl sulfate. In some embodiments, the composition does not contain or substantially does not contain alkyl sulfates. In some embodiments, the composition does not contain or substantially does not contain anionic surfactants. In some embodiments, the composition does not contain any surfactant other than alkyl glucoside and amine fluoride.

[0078] The mouthwash composition of the present invention contains water. The water used to prepare the mouthwash composition should be deionized and free of organic impurities. The water can constitute the remainder of the mouthwash composition. In some embodiments, the water is present in an amount of 70% to 99% by weight of the composition, such as 80% to 99%, 90% to 99%. This amount of water includes the added free water plus the amount introduced together with other components of the oral care composition such as sorbitol.

[0079] The mouthwash composition of the present invention may contain one or more humectants. The humectant can reduce evaporation and also contribute to preservation by reducing water activity, and can also impart a desired sweetness or flavor to the composition. Illustrative humectants can be or can include, but are not limited to: glycerol, propylene glycol, polyethylene glycol, sorbitol, xylitol, etc., or any mixture or combination thereof. In a preferred embodiment, the orally acceptable carrier can be or can include, but is not limited to, glycerol or sorbitol. In some embodiments, the humectant is selected from glycerol, sorbitol, and combinations thereof.

[0080] The mouthwash composition of the present invention may comprise a basic amino acid in free form or in salt form. Basic amino acids that can be used in the composition include not only naturally occurring basic amino acids such as arginine, lysine, and histidine, but also any basic amino acid having a carboxyl group and an amino group in the molecule, which is water-soluble and provides an aqueous solution with a pH of about 7 or higher. Thus, basic amino acids include, but are not limited to, arginine, lysine, citrulline, ornithine, creatine, histidine, diaminobutyric acid, diaminopropionic acid, their salts, or combinations thereof. In a particular embodiment, the basic amino acid is selected from arginine, lysine, citrulline, and ornithine. The basic amino acids of the oral care composition can generally be present in the L-form or L-configuration. The basic amino acid can be provided as a salt of a dipeptide or tripeptide containing the amino acid. In some embodiments, at least a portion of the basic amino acid present in the mouthwash composition is in salt form. In some embodiments, the basic amino acid is arginine (e.g., L-arginine) or its salt. Arginine can be provided as free arginine or its salt. For example, arginine can be provided as arginine phosphate, arginine hydrochloride, arginine sulfate, arginine bicarbonate, etc., and mixtures or combinations thereof. The basic amino acid can be provided as a solution or a solid. For example, the basic amino acid can be provided as an aqueous solution. In some embodiments, the amino acid comprises or is provided by an arginine bicarbonate solution. For example, the amino acid can be provided by a solution of about 40% of a basic amino acid (e.g., arginine bicarbonate or alternatively called arginine carbamate).

[0081] The mouthwash composition of the present invention may comprise a zinc ion source. The zinc ion source can be or include zinc ions and / or one or more zinc salts. For example, the zinc salt can be at least partially dissociated in an aqueous solution to produce zinc ions. Exemplary zinc salts can include, but are not limited to, zinc lactate, zinc oxide, zinc chloride, zinc phosphate, zinc citrate, zinc acetate, zinc borate, zinc butyrate, zinc carbonate, zinc formate, zinc gluconate, zinc glycerate, zinc glycolate, zinc picolinate, zinc propionate, zinc salicylate, zinc silicate, zinc stearate, zinc tartrate, zinc undecylenate, and mixtures thereof. In some embodiments, the zinc ion source is selected from zinc oxide, zinc citrate, and combinations thereof.

[0082] The mouthwash composition of the present invention may comprise a preservative. Suitable preservatives include, but are not limited to, sodium benzoate, potassium sorbate, methylisothiazolinone, parabens (e.g., methylparaben, propylparaben), and mixtures thereof. In certain embodiments, the preservative is sodium benzoate.

[0083] The mouthwash composition of the present invention may comprise a sweetening agent such as saccharin (e.g., sodium saccharin), acesulfame potassium, neotame, cyclamate or sucralose; a natural high-intensity sweetening agent such as thaumatin, stevioside or glycyrrhizin; or, for example, sorbitol, xylitol, maltitol or mannitol. In certain embodiments, the sweetening agent is saccharin, such as sodium saccharin.

[0084] The mouthwash composition of the present invention may comprise a flavoring agent. Suitable flavoring agents include, but are not limited to, essential oils and various flavored aldehydes, esters, alcohols and the like, as well as sweetening agents such as sodium saccharin. Examples of essential oils include oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit and orange. Such chemicals as menthol, carvone and anethole are also useful.

[0085] The mouthwash composition of the present invention may comprise one or more pH regulators. For example, the oral care composition may comprise one or more acidifying agents and / or one or more alkalizing agents configured to respectively decrease and / or increase its pH. Illustrative acidifying agents and / or one or more alkalizing agents may be or include, but are not limited to, the following: alkali metal hydroxides such as sodium hydroxide and / or potassium hydroxide, citric acid, hydrochloric acid, etc. or combinations thereof.

[0086] The mouthwash composition of the present invention may further comprise one or more buffering agents configured to control or adjust the pH within a predetermined or desired range. Illustrative buffering agents may include, but are not limited to, sodium bicarbonate, sodium phosphate, sodium carbonate, sodium acid pyrophosphate, sodium citrate and mixtures thereof. Sodium phosphate may include sodium dihydrogen phosphate (NaH2PO4), disodium hydrogen phosphate (Na2HPO4), trisodium phosphate (Na3PO4) and mixtures thereof. In a typical embodiment, the buffering agent may be anhydrous disodium hydrogen phosphate or disodium hydrogen phosphate and / or sodium dihydrogen phosphate. In another embodiment, the buffering agent comprises anhydrous disodium hydrogen phosphate or disodium hydrogen phosphate and phosphoric acid (e.g., syrupy phosphoric acid; 85%-food grade).

[0087] The mouthwash composition of the present invention may comprise an anti-calculus agent. Illustrative anti-calculus agents may include, but are not limited to, phosphates and polyphosphates (e.g., pyrophosphates), polyaminopropanesulfonic acid (AMPS), hexametaphosphates, zinc citrate trihydrate, polypeptides, polyolefin sulfonates, polyolefin phosphates, bisphosphonates. In some embodiments, the anti-calculus agent comprises tetrasodium pyrophosphate (TSPP), sodium tripolyphosphate (STPP) or a combination thereof.

[0088] The mouthwash composition of the present invention may comprise an antioxidant. Any orally acceptable antioxidant can be used, including but not limited to butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin A, carotenoids, vitamin E, flavonoids, polyphenols, ascorbic acid, herbal antioxidants, chlorophyll, melatonin, etc., or combinations and mixtures thereof.

[0089] All ingredients used in the compositions described herein should be orally acceptable. As used herein, "orally acceptable" can refer to any ingredient present in the composition in an amount and form that does not render the use of the composition unsafe in the oral cavity.

[0090] In another aspect, the present invention provides a method for (i) reducing or inhibiting the formation of dental caries, (ii) alleviating, repairing or inhibiting pre-carious lesions of tooth enamel, (iii) alleviating or inhibiting tooth demineralization and promoting tooth remineralization, (iv) alleviating tooth hypersensitivity, (v) alleviating or inhibiting gingivitis, (vi) promoting the healing of ulcers or wounds in the oral cavity, (vii) reducing the level of acid-producing bacteria, (viii) reducing or inhibiting the formation of microbial biofilms in the oral cavity, (ix) reducing or inhibiting the formation of plaque in the oral cavity, (x) promoting overall health or (xi) cleaning teeth and the oral cavity, the method comprising applying an effective amount of any one of the mouthwash compositions disclosed herein to the oral cavity of a subject in need thereof.

[0091] In another aspect, the present invention provides the use of any one of the mouthwash compositions disclosed herein in a subject in need thereof for: (i) reducing or inhibiting the formation of dental caries, (ii) alleviating, repairing or inhibiting pre-carious lesions of tooth enamel, (iii) alleviating or inhibiting tooth demineralization and promoting tooth remineralization, (iv) alleviating tooth hypersensitivity, (v) alleviating or inhibiting gingivitis, (vi) promoting the healing of ulcers or wounds in the oral cavity, (vii) reducing the level of acid-producing bacteria, (viii) reducing or inhibiting the formation of microbial biofilms in the oral cavity, (ix) reducing or inhibiting the formation of plaque in the oral cavity, (x) promoting overall health or (xi) cleaning teeth and the oral cavity.

[0092] In another aspect, the present invention provides the use of alkyl glucoside in any one of the mouthwash compositions comprising a fluorinated amine, such as the mouthwash compositions disclosed herein, for improving the micellar properties of the mouthwash composition, such as reducing the critical micelle concentration (CMC) of the fluorinated amine in the composition and / or decreasing the micelle (colloidal particle) size.

[0093] Examples

[0094] Prepare two solutions having the formulations shown in Table 1.

[0095] Table 1

[0096]

[0097] Formulation A contains amine fluoride (sodium monofluorophosphate) and cocoglucoside, while Formulation B contains sodium monofluorophosphate and PEG-40 hydrogenated castor oil, which is used as a surfactant in a commercial mouthwash (Elmex) formulation. The Elmex mouthwash contains 0.89% sodium monofluorophosphate and 0.27% PEG-40 hydrogenated castor oil. Once the surfactant concentration reaches a threshold called the critical micelle concentration (CMC), the surfactant forms micelles in solution. The CMC of sodium monofluorophosphate in Formulation A, Formulation B, and the Elmex mouthwash was determined from the inflection point of the surface tension isotherm, where the slope deviates from the linear decreasing portion. The surface tension was measured at room temperature using an Attension tensiometer. The results are shown in Table 2.

[0098] Table 2

[0099] Preparation CMC of oraftor (wt%) Elmax 1 A 0.005 B 0.09

[0100] The CMC of Formulation A was approximately 0.005%, while the CMC of Formulation B was 0.09%. In other words, the concentration of sodium monofluorophosphate in Formulation A was 180 times greater than its CMC, while the concentration of sodium monofluorophosphate in Formulation B was 10 times greater than its CMC. The lower CMC of Formulation A ensures a greater number of micelles. These results suggest that the combination of amine fluoride and cocoglucoside is a significantly improved alternative to amine fluoride / PEG-40 hydrogenated castor oil for micelle formation in mouthwash formulations. The CMC of the Elmex mouthwash was determined to be approximately 1%, although the inflection point of the surface tension curve of the Elmex mouthwash was not distinct.

[0101] Next, the colloidal particle (micelle) sizes of Formulation A, Formulation B, and the Elmex mouthwash were examined. The results are shown in Table 3.

[0102] Table 3

[0103]

[0104] The micelle size of formulation A was approximately 3.3 nm, significantly smaller than the micelle sizes of the individual fluoroamine (6.6 nm) and individual cocoglucoside (23.7 nm), indicating strong synergistic interactions between these two components. In contrast, the micelle size of formulation B was approximately 14.1 nm, close to the micelle size of PEG-40 hydrogenated castor oil (16.0 nm). Although the inflection point of the surface tension curve of Elmex mouthwash was not obvious, colloidal particles with a diameter of 12.2 nm were detected by dynamic light scattering, which may be solubilized oil droplets in the mouthwash product. Since the particle size of the fluoroamine / cocoglucoside complex was the smallest (fluoroamine / cocoglucoside < fluoroamine < fluoroamine / PEG-40 hydrogenated castor oil), its mobility was the strongest and it was very likely to reach smaller spaces that other substances could not reach. This feature was very likely to improve the delivery of the active substance encapsulated in the micelle core and also improve the availability of fluoroamine, thereby improving its antibacterial efficacy.

[0105] To further clarify the interaction between fluoroamine and other surfactants (alkyl glucoside or PEG-40 hydrogenated castor oil), 2D NOESY experiments were carried out. The results are shown in Figure 1 in. Figure 1 (Top) The cross peaks at approximately 2 ppm to 3 ppm in it indicated an interaction between the hydrocarbon chain of cocoglucoside and the head group of fluoroamine. However, no obvious interaction was found in formulation B ( Figure 1 , bottom). The diffusion rates of each component were further measured by NMR. The results are shown in Table 4.

[0106] Table 4. Diffusion rate D determined by NMR

[0107]

[0108] The results showed that when fluoroamine and cocoglucoside were mixed in formulation A, the molecular diffusion of the two components decreased to almost the same level, indicating that they formed aggregates. In contrast, the diffusion of fluoroamine and PEG-40 hydrogenated castor oil in formulation B did not change significantly compared with that in the individual solutions. These findings were consistent with the NOESY results shown in Figure 3 indicating that fluoroamine and alkyl glucoside interacted with each other to form aggregates.

[0109] Using a Q-Exactive equipped with a heated electrospray ionization source (HESI-II) TM Orbitrap TMA mass spectrometer (Thermo Scientific, San Jose, USA) was used to perform liquid chromatography-mass spectrometry (LCMS) analysis on a mixture of fluorinated amine and cocoglucoside. The samples were analyzed in full scan MS mode under negative polarity conditions using electrospray ionization. The results of the LCMS analysis are shown in Figure 2 and Figure 3 . As shown in Figure 2 and Figure 3 , complexes formed between the amine and cocoglucoside were detected, where the high-resolution mass spectra were consistent with the expected theoretical data for dodecyl glucoside plus amine bases (C18 ammonia and C16 ammonia), respectively. These results confirm that the fluorinated amine interacts with cocoglucoside to form a complex.

[0110] Although the present disclosure has been described with reference to the embodiments, those skilled in the art will understand that various modifications and variations can be made thereto without departing from the scope of the present disclosure as defined by the appended claims.

Claims

1. A mouthwash composition comprising a fluorinated amine, or an amine base and a fluoride, and an alkyl glucoside.

2. The composition according to claim 1, wherein the alkyl glucoside is C 8-25 alkyl glucoside.

3. The composition according to any one of the preceding claims, wherein the alkyl glucoside is selected from coco glucoside, decyl glucoside, caprylyl / capryl glucoside, lauryl glucoside, octyl glucoside, cetearyl glucoside, cetyl glucoside, hexadecyl glucoside, arachidyl glucoside, and combinations thereof.

4. The composition according to any one of the preceding claims, wherein the alkyl glucoside is coco glucoside.

5. The composition according to any one of the preceding claims, wherein the alkyl glucoside is present in an amount of 0.1% to 2.5% by weight of the composition.

6. The composition according to any one of the preceding claims, wherein the alkyl glucoside is present in an amount of 0.2% to 0.4% by weight of the composition.

7. The composition according to any one of the preceding claims, wherein the amine base is a linear or branched aliphatic amine or polyamine.

8. The composition according to any one of the preceding claims, wherein the amine base is a saturated or unsaturated C 12-20 alkylamine base or a saturated or unsaturated C 12-20 alkyl polyamine base.

9. The composition according to any one of the preceding claims, wherein the amine base is myristyl, palmityl, linoleyl, oleyl or stearyl amine or polyamine, or N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol), or N-octadec-9-enamine, and combinations thereof.

10. The composition according to any one of the preceding claims, wherein the amine base and the fluoride form a fluorinated amine in situ.

11. The composition according to any one of the preceding claims, wherein the fluorinated amine is orabase (N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride).

12. The composition according to any one of the preceding claims, wherein the fluorinated amine is present in an amount of 0.5% to 1.5% by weight of the composition.

13. The composition according to any one of the preceding claims, wherein the fluorinated amine is present in an amount of 0.8% to 1.2% by weight of the composition.

14. The composition according to any one of the preceding claims, wherein the composition comprises orabase in an amount of 0.8% to 1.2% by weight of the composition and coco glucoside in an amount of 0.2% to 0.4% by weight of the composition.

15. The composition according to any one of the preceding claims, wherein the composition does not contain or substantially does not contain sodium lauryl sulfate.

16. The composition according to any one of the preceding claims, wherein the composition does not contain or substantially does not contain an anionic surfactant.

17. Use of an alkyl glucoside in a mouthwash composition comprising a fluorinated amine for improving the micellar properties of the mouthwash composition.

18. The use according to claim 17, wherein the improvement of the micellar properties of the mouthwash composition comprises reducing the critical micelle concentration (CMC) of the fluorinated amine in the composition and / or reducing the micelle (colloidal particle) size.

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