Agent for promoting retention of bactericidal component on tooth surface

Abstract

To provide a bactericidal component retention promoter that is capable of promoting the retention of a bactericidal component on tooth surfaces.SOLUTION: The present invention provides a bactericidal component retention promoter that is capable of promoting the retention of a bactericidal component on tooth surfaces, containing (A) a bivalent metal ion source and (B) a chelator, where the bactericidal component is a quaternary ammonium salt containing a benzene ring, as well as an oral composition that contains the bactericidal component retention promoter and a quaternary ammonium salt containing a benzene ring, serving as a bactericidal component.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for promoting retention of a bactericidal component on a tooth surface. [Background technology]

[0002] Conventionally, research has been conducted on the development of technology to prevent dental caries and periodontal disease, which are the two major oral diseases, by adding a bactericide to oral compositions such as dentifrice, and oral compositions containing the bactericide have been marketed. The bactericide can reduce the total number of bacteria in the oral cavity and inhibit the formation of plaque, which causes diseases. However, because it is difficult for drugs such as bactericides to remain sufficiently in the oral cavity due to the self-cleaning action of gargling and saliva, the bactericidal effect is often temporary, and a sustained bactericidal effect in the oral cavity is required. To address this issue, several studies have been conducted to improve the retention of bactericides by adding polymeric compounds such as cationic polymers and crystalline cellulose (Patent Documents 1 and 2). However, when a polymer compound is blended in an oral composition, the composition becomes viscous, making it difficult to disperse during use, which causes a problem of poor usability. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2000-034213 A [Patent Document 2] JP 2002-179541 A Summary of the Invention [Problem to be solved by the invention]

[0004] One object of the present invention is to provide a bactericidal component retention promoter that can maintain the bactericidal effect for a long period of time by adsorbing the bactericidal component to the tooth surface and not being washed away by gargling or saliva, regardless of the addition of a polymer compound. An object of the present invention is to provide an oral composition containing the above-mentioned bactericidal component retention promoter. [Means for solving the problem]

[0005] As a result of intensive research aimed at solving the above problems, the inventors discovered that a formulation containing (A) a divalent metal ion source and (B) a chelating agent can extend the residence time of a bactericidal component on the tooth surface, thereby arriving at the present invention.

[0006] Possible embodiments of the present invention include the following. [1] A bactericidal component retention promoter for promoting retention of a bactericidal component on a tooth surface, characterized in that it contains (A) a divalent metal ion source and (B) a chelating agent, wherein the bactericidal component is a quaternary ammonium salt containing a benzene ring. [2] The bactericidal component retention promoter according to [1], wherein the (A) divalent metal ion source is a divalent metal ion source having a halogen element. [3] The bactericidal component retention promoter according to [2], wherein the divalent metal ion source having a halogen element is stannous fluoride. [4] The bactericidal component retention promoter according to any one of [1] to [3] above, wherein the bactericidal component is benzalkonium chloride or benzethonium chloride. [5] The bactericidal component retention promoter according to any one of [1] to [4] above, wherein the (B) chelating agent is a carboxylic acid or a salt thereof. [6] The bactericidal component retention promoter according to [5], wherein the carboxylic acid or its salt is gluconic acid or lactic acid. [7] The (A) divalent metal ion source is stannous fluoride, The (B) chelating agent is gluconic acid or lactic acid, and The bactericidal component retention promoter according to any one of [1] to [6] above, wherein the bactericidal component is benzalkonium chloride or benzethonium chloride. [8] The bactericidal component retention promoter according to any one of [1] to [7], wherein when the content of the (A) divalent metal ion source is A [% by mass] and the content of the (B) chelating agent is B [% by mass], A:B satisfies a relationship of 1:0.0033 to 1:500. [9] The bactericidal component retention promoter according to any one of [1] to [8], wherein when the content of the (A) divalent metal ion source is A [% by mass] and the content of the quaternary ammonium salt containing a benzene ring as the bactericidal component is C [% by mass], A:C satisfies a relationship of 1:0.000167 to 1:100.

[10] An oral composition for promoting retention of a bactericidal component on a tooth surface, comprising (C) a quaternary ammonium salt containing a benzene ring as a bactericidal component and the bactericidal component retention promoter described in any one of [1] to [9] above.

[11] The (A) divalent metal ion source is contained in an amount of 0.01% by mass to 3% by mass based on the total mass of the oral composition; The (B) chelating agent is contained in an amount of 0.01% by mass to 5% by mass based on the total mass of the oral cavity composition, and The oral composition according to

[10] , comprising (C) a quaternary ammonium salt containing a benzene ring in an amount of 0.0005% by mass to 1% by mass based on the total mass of the oral composition.

[12] The oral composition according to

[10] or

[11] , which is a dentifrice, a mouthwash, or an oral moisturizer.

[13] The oral composition according to any one of

[10] to

[12] above, which is a dentifrice selected from toothpaste, gel dentifrice, and liquid dentifrice. Effect of the Invention

[0007] According to the present invention, by combining a bactericidal component, particularly a quaternary ammonium salt containing a benzene ring such as benzalkonium chloride or benzethonium chloride, with a divalent metal ion source such as stannous fluoride and a chelating agent such as gluconic acid or lactic acid, it is possible to provide an agent for promoting retention of a bactericidal component on tooth surfaces, which allows the bactericidal component to remain significantly on the tooth surface. Furthermore, according to the present invention, it is possible to provide an oral composition such as a dentifrice, a mouthwash, or an oral moisturizer which contains the above-mentioned bactericidal component and the above-mentioned agent for promoting retention of the bactericidal component on the tooth surface. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] The present invention will be described in detail below. Note that the preferred and more preferred embodiments exemplified below can be used in appropriate combination with each other regardless of the expressions such as "preferred" and "more preferred". Furthermore, the description of the numerical range is merely an example, and ranges obtained by appropriately combining the upper and lower limits of each range and the numerical values ​​of the examples can also be preferably used. Furthermore, the terms "contain" or "include" may be read as "essentially consisting of" or "consisting only of".

[0009] [Agent that promotes retention of antibacterial ingredients on tooth surfaces] The agent for promoting retention of a bactericidal component on a tooth surface according to the present invention is characterized by comprising (A) a divalent metal ion source and (B) a chelating agent.

[0010] In the present specification, the term "antimicrobial component retention promoter on tooth surface" refers to a preparation that allows an antimicrobial component such as a quaternary ammonium salt containing a benzene ring to remain on the tooth surface for a long period of time, in other words, a preparation that can increase the amount of antimicrobial component that can remain on the tooth surface for a certain period of time compared to when the antimicrobial component retention promoter is not present. The tooth surface may be the upper surface, side surface, inner and outer surface of the tooth, and further includes the surface of the tooth hidden by the gums. More specifically, the tooth surface refers to the enamel tooth surface, more preferably the surface of the crown. In the test, apatite beads (apatite beads) may be used as a tooth substitute. The retention promotion is, for example, that 2 hours after the application of the antimicrobial component to the tooth surface, 25% by mass or more of the antimicrobial component remains compared to the time immediately after application to the tooth surface, preferably 30% by mass or more remains, and more preferably 40% by mass or more remains. The antimicrobial component is, for example, a quaternary ammonium salt containing a benzene ring, more preferably benzalkonium chloride or benzethonium chloride. These bactericidal components may be one type of component or a combination of two or more components. Other bactericidal and antibacterial components used for sterilization of teeth and the oral cavity may also be used alone or in combination with the above bactericidal components.

[0011] Examples of other bactericidal and antibacterial components that can be used include cationic bactericides, nonionic bactericides, and amphoteric bactericides. Examples of cationic bactericides include quaternary ammonium salts such as cetylpyridinium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, stearyltrimethylammonium chloride, cetyltrimethylammonium chloride, lauryltrimethylammonium chloride, and laurylpyridinium chloride; and cationic bactericides such as biguanide bactericides such as alexidine gluconate, alexidine hydrochloride, alexidine acetate, chlorhexidine hydrochloride, chlorhexidine acetate, and chlorhexidine gluconate. Examples of nonionic bactericides include phenol bactericides such as isopropylmethylphenol, triclosan, hinokitiol, phenol, thymol, eugenol, and bisphenol. Examples of amphoteric bactericides include dodecyldiaminoethylglycine. These other bactericidal and antibacterial components may be used alone or in combination of two or more.

[0012] (A) Divalent metal ion source The "divalent metal ion source" described in this specification is a compound that releases divalent metal ions. Examples of divalent metal ion sources include stannous fluoride, stannous chloride, stannous bromide, stannous iodide, copper(II) fluoride, copper(II) chloride, copper(II) bromide, copper(II) iodide, copper gluconate, copper chlorophyllin sodium, zinc fluoride, zinc chloride, zinc bromide, zinc iodide, zinc oxide, and zinc glycine. Among these, divalent metal ion sources having halogen elements are preferred. For example, compounds having halogen elements as ligands or counter ions and dissolving in water to release divalent metal ions are more preferred, specifically stannous fluoride, stannous chloride, stannous bromide, stannous iodide, copper(II) fluoride, copper(II) chloride, copper(II) bromide, copper(II) iodide, zinc fluoride, zinc chloride, zinc bromide, zinc iodide, etc., and stannous fluoride is particularly preferred. Stannous fluoride is a compound represented by the chemical formula SnF2 that exists as white crystals at room temperature (e.g., 25°C±5°C). The component (A) is used as a component that is adsorbed to the tooth surface, in other words, as a component that promotes (assists) the adsorption of the bactericidal component to the tooth surface. The component (A) itself has bactericidal activity and can be used as a bactericidal component. The bactericidal component retention promoter may contain the component (A) in an amount based on the total mass of the bactericidal component retention promoter and such that the total of all components contained in the bactericidal component retention promoter does not exceed 100 mass%, for example, 1 mass% to 80 mass%, preferably 5 mass% to 60 mass%, more preferably 10 mass% to 50 mass%, and particularly preferably 15 mass% to 45 mass%. The component (A) may be used alone or in combination of two or more kinds. When the content of the (A) component in the bactericidal component retention promoter is A [mass %] and the content of the quaternary ammonium salt containing a benzene ring as the bactericidal component is C [mass %], it is preferable that A:C satisfies the relationship of 1:0.000167 to 1:100, more preferably satisfies the relationship of 1:0.0005 to 1:2.5, particularly preferably satisfies the relationship of 1:0.005 to 1:0.1, and most preferably satisfies the relationship of 1:0.0125 to 1:0.025. By containing them in such a ratio, the chelating agent effectively stabilizes the divalent metal ion, and effects such as maintaining the bactericidal and antibacterial activity of the divalent metal ion and improving the appearance stability can be obtained.

[0013] (B) Chelating agent The term "chelating agent" as used herein means a compound capable of binding (coordinating) to a metal ion via a ligand having multiple coordination sites to form a complex. More specifically, the chelating agent is a compound capable of binding to a divalent metal ion from component (A) to form a complex. Examples of chelating agents include gluconic acid, lactic acid, malic acid, tartaric acid, citric acid, succinic acid, adipic acid, etidronic acid, ethylenediaminetetraacetic acid, phytic acid, oxalic acid, phthalic acid, fumaric acid, pyruvic acid, maleic acid, mandelic acid, aspartic acid, glutamic acid, glycolic acid, ascorbic acid, caproic acid, anisic acid, benzoic acid, sorbic acid, pantothenic acid, crotonic acid, cinnamic acid, polyphosphoric acid, pyrophosphoric acid, and metaphosphoric acid, as well as their sodium, potassium, calcium, and magnesium salts. Among them, carboxylic acids or their salts are preferred, and examples of the carboxylic acids or their salts include gluconic acid, lactic acid, malic acid, tartaric acid, citric acid, succinic acid, adipic acid, etidronic acid, ethylenediaminetetraacetic acid, oxalic acid, phthalic acid, fumaric acid, pyruvic acid, maleic acid, mandelic acid, aspartic acid, glutamic acid, glycolic acid, ascorbic acid, caproic acid, anisic acid, benzoic acid, sorbic acid, pantothenic acid, crotonic acid, and cinnamic acid, as well as their sodium salts, potassium salts, calcium salts, and magnesium salts, and particularly preferred is gluconic acid or lactic acid. Gluconic acid has the chemical formula CH 12 It is a compound represented by the chemical formula C3H6O3. Component (B) can be used to maintain the bactericidal / antibacterial activity of the divalent metal ion and improve the stability of the appearance by binding to the divalent metal ion derived from component (A). The bactericidal component retention promoter may contain component (B) in an amount not exceeding 100 mass% in total of all components contained in the bactericidal component retention promoter, for example, 10 to 99 mass%, preferably 25 to 95 mass%, more preferably 40 to 90 mass%, and particularly preferably 50 to 85 mass%, based on the total mass of the bactericidal component retention promoter. Component (B) may be used alone or in combination of two or more kinds.

[0014] The contents of the (A) component and the (B) component in the bactericidal component retention promoter, where the content of the (A) component is A [mass %] and the content of the (B) component is B [mass %], preferably satisfy a relationship of 1:0.0033 to 1:500, more preferably satisfy a relationship of 1:0.05 to 1:75, particularly preferably satisfy a relationship of 1:1 to 1:20, and most preferably satisfy a relationship of 1:1.25 to 1:12.5. By containing them in such a ratio, the chelating agent effectively stabilizes the divalent metal ion, and effects such as maintaining the bactericidal and antibacterial activity of the divalent metal ion and improving the appearance stability can be obtained. Furthermore, when the content of component (B) and the content of the bactericidal component in the bactericidal component retention promoter are B [% by mass] and C [% by mass], respectively, the content of component (B) and the content of the bactericidal component having a benzene ring preferably satisfy a relationship of 0.01:1 to 10,000:1, more preferably a relationship of 1:1 to 3,000:1, particularly preferably a relationship of 50:1 to 400:1, and most preferably a relationship of 100:1 to 250:1.

[0015] Optional ingredients In addition to the above-mentioned (A) and (B) components, the bactericidal component retention promoter of the present invention may contain optional components as necessary. Examples of optional components include surfactants, abrasives, thickeners, wetting agents, solvents, sweeteners, flavorings, cooling agents, pH adjusters, preservatives, coloring agents, suspending agents, functional components, and flavoring components. These optional components may be appropriately selected within a range that does not impair the effects of the present invention, and may be blended in an appropriate blending amount. These optional components may be compounds that have multiple characteristics (for example, a flavoring and a cooling agent, etc.).

[0016] Examples of surfactants include sodium lauryl sulfate, sodium α-olefin sulfonate, sodium dodecylbenzenesulfonate, sodium lauryl sulfoacetate, sodium N-lauroyl sarcosinate, N-acyl glutamate, sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene block copolymer, alkyl glycosides, sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, alkyl dimethylamine oxide, lauryl ethanolamide, sodium cocoyl sarcosinate, sodium N-lauroyl methyl taurine solution, etc. The amount of the surfactant is generally 0.01% by mass to 10% by mass based on the total mass of the bactericidal component retention promoter.

[0017] Examples of the abrasive include calcium carbonate, calcium phosphate, dibasic calcium phosphate, calcium pyrophosphate, insoluble calcium metaphosphate, hydrous silicic acid, anhydrous silicic acid, titanium dioxide, amorphous silica, crystalline silica, aluminosilicate, aluminum oxide, aluminum hydroxide, resin, etc. The amount of the abrasive is generally 0.01% by mass to 50% by mass based on the total mass of the bactericidal component retention promoter. Examples of thickeners include cellulose derivatives such as carrageenan, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose, alkali metal alginates such as sodium alginate, propylene glycol alginate, gums such as xanthan gum, tragacanth gum, and gum arabic, synthetic thickeners such as polyvinyl alcohol, sodium polyacrylate, and polyvinylpyrrolidone, and inorganic thickeners such as silica gel, aluminum silica gel, and Veegum, etc. The amount of the thickener to be blended is generally 0.01% by mass to 30% by mass based on the total mass of the bactericidal component retention promoter. Examples of the wetting agent include polyhydric alcohols such as glycerin, sorbitol, polyethylene glycol, propylene glycol, ethylene glycol, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, etc. The amount of the wetting agent is generally 0.01% by mass to 99% by mass based on the total mass of the bactericidal component retention promoter.

[0018] Examples of the solvent include organic solvents such as ethanol, propyl alcohol, isopropyl alcohol, etc., water, etc. The blending amount thereof is generally 0.01% by mass to 99% by mass based on the total mass of the bactericidal component retention promoter. Examples of sweeteners include palatinit, aspartame, sodium saccharin, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillarmine, thaumatin, aspartyl phenylalanyl methyl ester, p-methoxycinnamic aldehyde, sucralose, xylitol, stevia, etc. The amount of the sweetener is generally 0.001% by mass to 10% by mass based on the total mass of the bactericidal component retention promoter. Examples of the flavoring include blended flavorings such as strawberry flavor and apple flavor, terpenoid essential oils, phenylpropanoid essential oils, and the like. Examples of cooling agents include N-ethyl-p-menthane-3-carboxamide, ethyl-3-(p-menthane-carboxamide) acetate, N-(4-cyanomethylphenyl)-p-menthanecarboxamide, etc. The amount of the agent is generally 0.001% by mass to 5% by mass based on the total mass of the bactericidal component retention promoter. Examples of pH adjusters include phosphoric acid, pantothenic acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, silicic acid, citric acid, metaphosphoric acid, polyphosphoric acid, and chemically possible salts thereof, as well as sodium hydroxide, potassium hydroxide, etc. The amount of the pH adjuster is generally 0.001% by mass to 20% by mass based on the total mass of the bactericidal component retention promoter.

[0019] Examples of preservatives include paraoxybenzoic acid esters, benzoic acid and its salts, salicylic acid and its salts, sorbic acid and its salts, phenoxyethanol, alkyldiaminoethylglycine hydrochloride, etc. The amount of the preservative is generally 0.001% by mass to 10% by mass based on the total mass of the bactericidal component retention promoter. Examples of colorants include dyes such as Blue No. 1, Green No. 3, Yellow No. 4, and Red No. 105, as well as pigments such as titanium dioxide, zinc oxide, and gunjo. The amount of the colorant blended is generally 0.01% by mass to 10% by mass based on the total mass of the bactericidal component retention promoter. Examples of suspending agents include oils and fats such as olive oil, camellia oil, castor oil, and emulsions containing these oils and fats. The amount of the suspending agent is generally 0.001% by mass to 5% by mass based on the total mass of the bactericidal component retention promoter. Examples of functional ingredients include glycyrrhizic acid and its salts, glycyrrhetinic acid, pyridoxine hydrochloride, ε-aminocaproic acid, allantoin, sodium chloride, ascorbic acid and its salts, ascorbic acid derivatives, tocopherol acetate, zeolite, sodium fluoride, sodium monofluorophosphate, polyethylene glycol, potassium nitrate, azulene sulfonic acid and its salts, aluminum lactate, and tranexamic acid. The amount of the functional ingredient is generally 0.001% by mass to 10% by mass based on the total mass of the bactericidal component retention promoter. Examples of the flavoring component include tea extract, dry distillation liquid of tea, sodium glutamate, etc. The blending amount is generally 0.001% by mass to 5% by mass based on the total mass of the bactericidal component retention promoter.

[0020] The bactericidal component retention promoter of the present invention can be in various forms such as solid, powder, paste, gel, liquid, etc. at room temperature (eg, 25° C.±5° C.).

[0021] The bactericidal component retention promoter on the tooth surface in this specification can be used for the purpose of extending the time that the bactericidal component can remain on the tooth surface, in other words, for the purpose of increasing the amount of the bactericidal component that can remain on the tooth surface within a certain period of time. It can also be used for the purpose of increasing the amount of the bactericidal component that can remain on the tooth surface without being washed away by gargling or saliva. The bactericidal component referred to here is a quaternary ammonium salt containing a benzene ring, more preferably benzalkonium chloride or benzethonium chloride. The amount of the bactericidal component relative to the bactericidal component retention promoter in this specification is based on the total mass of the bactericidal component retention promoter and the quaternary ammonium salt containing a benzene ring as the bactericidal component, and the total amount of the total components does not exceed 100% by mass, and may be preferably 0.005% by mass to 10% by mass, more preferably 0.01% by mass to 1% by mass, and particularly preferably 0.05% by mass to 0.8% by mass.

[0022] [Oral composition] The present invention may be an oral composition comprising the bactericidal component retention promoter on the tooth surface as described above and (C) a quaternary ammonium salt containing a benzene ring as a bactericidal component. The oral composition may be an oral composition capable of promoting retention of the bactericidal component (C) on the tooth surface by the action of the bactericidal component retention promoter. The oral composition is preferably a composition used for inhibiting bacteria present on the tooth surface for a long period of time. Here, examples of bacteria include facultative anaerobic gram-positive cocci such as dental caries bacteria (Streptococcus mutans), obligate anaerobic gram-negative bacteria such as periodontal disease bacteria (Porphyromonas gingivalis), and fungi such as Candida albicans. In particular, dental caries bacteria have a strong ability to adhere to the tooth surface, so the oral composition is useful in that a specific bactericidal component can be retained on the tooth surface for a long period of time.

[0023] (C) Quaternary ammonium salts containing a benzene ring The "quaternary ammonium salt containing a benzene ring" described in this specification is a quaternary ammonium salt that has the effect of being a bactericidal component and contains one or more benzene rings. The benzene ring may be unsubstituted or may be substituted with any substituent. Examples of the quaternary ammonium salt containing a benzene ring include benzalkonium chloride, benzethonium chloride, dequalinium chloride, etc., and benzalkonium chloride or benzethonium chloride is preferred.

[0024] Benzalkonium chloride has the chemical formula C6H5CH2N + (CH3)2R Cl - (R=C8H 17 ~C 18 H 37 ) and has the following structural formula: TIFF2025007673000001.tif4452

[0025] Benzethonium chloride has the chemical formula C 27 H 42 It is a compound represented by ClNO2 and has the following structural formula: TIFF2025007673000002.tif49138

[0026] The oral composition may contain the component (A) in an amount of preferably 0.01% by mass to 3% by mass, more preferably 0.04% by mass to 2% by mass, and particularly preferably 0.1% by mass to 1% by mass, based on the total mass of the oral composition. The oral composition may contain the component (B) in an amount of preferably 0.01% by mass to 5% by mass, more preferably 0.1% by mass to 3% by mass, and particularly preferably 1% by mass to 2% by mass, based on the total mass of the oral composition. The oral composition contains the component (C) in an amount of preferably 0.0005% by mass to 1% by mass, more preferably 0.001% by mass to 0.1% by mass, and particularly preferably 0.005% by mass to 0.01% by mass, based on the total mass of the oral composition. The component (C) may be used alone or in combination of two or more kinds. Other antibacterial and antimicrobial ingredients In addition to the above-mentioned components (A), (B), and (C), the oral composition of the present invention may contain other bactericidal and / or antibacterial components other than component (A) or component (C) as necessary. Other bactericidal and antibacterial components include the other bactericidal and antibacterial components described above. These antibacterial components may be used alone or in combination of two or more. The amount of the antibacterial component is generally 0.001% by mass to 10% by mass based on the total mass of the oral composition.

[0027] Optional ingredients The oral composition of the present invention may contain optional components as necessary in addition to the above-mentioned components (A), (B), and (C). The optional components include, for example, the above-mentioned surfactants, abrasives, thickeners, humectants, solvents, sweeteners, flavorings, cooling agents, pH adjusters, preservatives, colorants, suspending agents, functional components, and flavoring components that can be used in the bactericidal component retention promoter. The oral composition may also be prepared without the abrasive. These optional components may be appropriately selected within a range that does not impair the effects of the present invention, and may be blended in an appropriate blending amount as described above. However, in the blending amount of the optional components in the above-mentioned bactericidal component retention promoter, "based on the total mass of the bactericidal component retention promoter" should be read as "based on the total mass of the oral composition." These optional components may be a single compound having multiple characteristics (for example, a flavoring and a cooling agent). Furthermore, the optional components contained in the oral composition may be the same or different in part or in whole from the optional components of the bactericidal component retention promoter described above. The oral composition of the present invention can be in various forms such as paste, gel, liquid, etc. at room temperature (e.g., 25°C ± 5°C). Specifically, the oral composition of the present invention can be prepared as a dentifrice, mouthwash, oral moisturizer, etc. When the oral composition of the present invention is a dentifrice, it may be a toothpaste, gel dentifrice, or liquid dentifrice. The oral composition of the present invention does not turn brown, and has a uniform white, slightly cloudy, or transparent appearance. It may also be colored to any color tone with a colorant.

[0028] The bactericidal component retention promoter and oral composition described in this specification may contain a polymeric compound, but preferably, in view of the purpose of the present invention, it is appropriate that they do not contain the polymeric compound. Here, examples of the polymeric compound include cationic polymers, anionic polymers, crystalline cellulose, etc. When a polymeric compound is contained, it is appropriate that the content of the polymeric compound is, for example, 1% by mass or less, preferably 0.1% by mass or less, more preferably 0.01% by mass or less, based on the total content of the bactericidal component retention promoter and oral composition.

[0029] [Manufacturing method] The bactericidal component retention promoter of the present invention can be produced by a method including a step of mixing (A) a divalent metal ion source, (B) a chelating agent, and, if necessary, optional components. The order of mixing the components (A) to (B) and optional components is not particularly limited, and each component may be mixed in order or simultaneously. The bactericidal component retention promoter of the present invention can also be formulated into any form. Similarly, the oral composition of the present invention can be produced by a method including a step of mixing (A) a divalent metal ion source, (B) a chelating agent, and (C) a quaternary ammonium salt containing a benzene ring. The order of mixing the components (A) to (C) and any optional components is not particularly limited, and the components may be mixed one by one, or the three components and any optional components may be mixed simultaneously. In addition to the above-mentioned mixing step, the oral composition of the present invention can be formulated into any form by blending other bactericidal / antibacterial components and optional components according to a method commonly used in the manufacture of oral compositions.

[0030] [Methods to promote retention of antibacterial ingredients on tooth surfaces] A method for promoting the retention of a bactericidal component on a tooth surface is provided using the bactericidal component retention promoter and / or oral composition of the present invention. When a bactericidal component retention promoter is used, the retention of the bactericidal component is promoted when the combined components are applied to a tooth surface by combining the bactericidal component retention promoter, the bactericidal component, and any other components. When an oral composition is used, the retention of the bactericidal component is promoted when the bactericidal component is applied to a tooth surface as is or in combination with any other components. The retention promotion is, for example, that 25% by mass or more of the bactericidal component remains on the tooth surface 2 hours after the application of the bactericidal component, compared to immediately after application to the tooth surface, preferably 30% by mass or more remains, and more preferably 40% by mass or more remains. Here, the definitions of the tooth surface and the bactericidal component are as described above. EXAMPLES

[0031] Specific examples of the oral composition of the present invention will be described below, but it should be clearly noted that these examples are not intended to limit the scope of the present invention. In the following examples and comparative examples, the unit of blend amount is mass % unless otherwise specified.

[0032] [sample] The raw materials and the like used in the test examples described below are explained in detail below. Artificial saliva: an aqueous solution containing 0.9 mM potassium dihydrogen phosphate, 1.5 mM calcium chloride, 20 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), and 130 mM potassium chloride at a pH of 7. Extraction solvent A: A mixed solution of acetonitrile, tetrahydrofuran, and sodium perchlorate solution in a mass ratio of 4:2:9. The sodium perchlorate solution used here is a 0.7% aqueous solution of sodium perchlorate manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Benzalkonium chloride: NOF Corporation

[0033] [Test Method] The conditions of the high performance liquid chromatography used for the quantitative determination of the samples are as follows. Detector: Ultraviolet spectrophotometer (measurement wavelength: 215 nm) Mobile phase: sodium perchlorate solution / acetonitrile = 6:4 Column: Stainless steel tube packed with silica gel bonded with sulfonic acid groups for liquid chromatography Column temperature: constant temperature around 40℃

[0034] [Test Example 1] Residual rate of benzalkonium chloride in apatite beads First, each component of the Examples and Comparative Examples shown in Tables 1 and 2 below was dissolved in water, and then the pH was adjusted to 5.5 to 6.0 with sodium hydroxide to prepare test samples for each of the Examples and Comparative Examples. Next, 0.1 g of the above-mentioned apatite beads (apatite beads) was weighed and added to a test tube, and 1 mL of each of the above-mentioned test samples was added. The test tube was left at room temperature (25°C) for 2 hours, the test samples were fully immersed in the apatite beads, and the supernatant was collected from the test tube. The remaining apatite beads were washed 8 times with 0.5 mL of the above-mentioned artificial saliva, and the artificial saliva after washing was collected. The collected supernatant and the artificial saliva after washing were combined, and the extraction solvent A was added to the collected solution, and the volume was adjusted to 20 mL to obtain a sample solution. In a separate container, 1 mL of the test sample of each Example and Comparative Example was placed, and artificial saliva and extraction solvent A were further added, and the volume was adjusted to 20 mL to prepare a stock solution. Benzalkonium chloride was dissolved in water to a concentration of 1000 μg / mL, 100 μg / mL, or 10 μg / mL, and this was further diluted 10-fold with extraction solvent A to a final concentration of 100 μg / mL, 10 μg / mL, or 1 μg / mL to prepare the standard solutions.

[0035] The sample solutions of each test sample, the undiluted solutions of each test sample, and the standard solutions were measured by the above-mentioned high performance liquid chromatography to quantify benzalkonium chloride. A calibration curve was created from the peak area obtained from the standard solution. The concentrations of each sample solution and each stock solution were calculated from the calibration curve, and the amount of benzalkonium chloride in the recovered solution was calculated by multiplying the concentration of each sample solution by its volume (20 mL), and the amount of benzalkonium chloride in the test sample was calculated by multiplying the concentration of each stock solution by its volume (20 mL). The remaining amount and remaining rate of benzalkonium chloride in the apatite beads were calculated using the following formula. Amount of benzalkonium chloride in the collected solution (μg) = concentration of each sample solution (μg / mL) × volume (20 mL) Amount of benzalkonium chloride in the test sample (μg) = concentration of each stock solution (μg / mL) × volume (20 mL) Amount of benzalkonium chloride remaining on apatite beads (μg) = Amount of benzalkonium chloride in test sample (μg) - Amount of benzalkonium chloride in recovered solution (μg) Residual rate of benzalkonium chloride in apatite beads (%) = remaining amount of benzalkonium chloride in apatite beads (μg) / amount of benzalkonium chloride in test sample (μg) × 100 The obtained residual rate was judged according to the following criteria. ◎ (Best): Benzalkonium chloride remaining rate (%) is 30% or more ○ (Good): Benzalkonium chloride remaining rate (%) is 25% or more and less than 30% × (Not acceptable): The residual rate (%) of benzalkonium chloride is less than 25%.

[0036] The evaluation results for each of the examples and comparative examples are shown in Tables 1 and 2. In Tables 1 and 2, "A:B" indicates the ratio of the content A [mass%] of component (A) to the content B [mass%] of component (B). "A:C" indicates the ratio of the content A [mass%] of component (A) to the content C [mass%] of component (C) or benzalkonium chloride as a bactericidal component. "B:C" indicates the ratio of the content A [mass%] of component (B) to the content C [mass%] of component (C) or benzalkonium chloride as a bactericidal component.

[0037] [Table 1] [Table 2]

[0038] From Example 1 and Comparative Examples 1 to 4, it was revealed that the amount and rate of the bactericidal component remaining on the tooth surface are improved by using a bactericidal component retention promoter containing components (A) and (B) for the bactericidal component. Comparing Examples 1, 4, and 5 with Comparative Example 3, it can be said that the (A) component is preferably present in the oral composition at about 0.1 to 1 mass %, and more preferably at about 0.4 to 1 mass %. Furthermore, comparing Examples 1, 6, and 7 with Comparative Example 2, it can be said that the (B) component is particularly preferably present in the oral composition at about 1 to 2 mass %.

[0039] [Prescription example] The following shows an example of a formulation of an oral composition containing the bactericidal component retention promoter of the present invention, which is prepared by mixing each component described in this specification. The unit of blending amount is mass % when the entire formulation is 100 mass %.

[0040] <Formulation example 1: Gel toothpaste> Stannous fluoride 0.4 Gluconic acid 1.25 Lactic acid 1.25 Benzalkonium chloride 0.01 Benzethonium chloride 0.01 Sodium carboxymethylcellulose 0.1 Hydroxyethyl cellulose 1.0 Sodium hydroxide 0.40 Sodium fluoride 0.1 Propylene glycol alginate 0.3 70% Sorbitol Solution 10 Concentrated glycerin 30 Dipotassium glycyrrhizinate 0.1 Isopropyl methylphenol 0.1 Sodium Lauroyl Sarcosinate 0.1 Polyoxyethylene hydrogenated castor oil 0.5 Glycerin fatty acid ester 0.5 Sodium hyaluronate 0.01 Fragrance 1.0 Purified water remainder Total 100%

[0041] <Formulation Example 2: Toothpaste> Stannous fluoride 0.4 Gluconic acid 1.25 Lactic acid 1.25 Benzalkonium chloride 0.01 Benzethonium chloride 0.01 Silica 7 Hydrated Silica 3 Calcium hydrogen phosphate 1 Titanium dioxide 0.3 Sodium carboxymethylcellulose 1.5 Sodium hydroxide 0.3 Sodium fluoride 0.1 Sodium saccharin 0.1 Sodium Lauryl Sulfate 1.5 Sodium Methyl Lauroyl Taurate 0.5 Isopropyl methylphenol 0.1 Pyridoxine hydrochloride 0.1 70% Sorbitol Solution 10 Concentrated glycerin 20 Polyoxyethylene hydrogenated castor oil 1.0 Fragrance 1.0 Purified water remainder Total 100%

[0042] <Formulation example 3: Liquid dentifrice> Stannous fluoride 0.4 Gluconic acid 1.25 Lactic acid 1.25 Benzalkonium chloride 0.01 Benzethonium chloride 0.01 Xanthan gum 0.5 Sodium hydroxide 0.42 Xylitol 1 Propylene glycol alginate 0.1 Dipotassium glycyrrhizinate 0.1 Sorbitol 7 Concentrated glycerin 30 Polyoxyethylene hydrogenated castor oil 0.5 Fragrance 1.0 Purified water remainder Total 100%

[0043] <Formulation Example 4: Non-aqueous toothpaste> Stannous fluoride 0.4 Gluconic acid 1.25 Lactic acid 1.25 Benzalkonium chloride 0.01 Benzethonium chloride 0.01 Silica 10 Hydrated Silica 5 Calcium hydrogen phosphate 1 Titanium dioxide 1 Propylene glycol alginate 0.1 Hydroxyethylcellulose 1 Sodium Carboxymethylcellulose 1 Hydroxypropyl cellulose 1 Hydroxypropyl methylcellulose 1 Polyvinylpyrrolidone 1 Sodium hydroxide 0.3 Sodium fluoride 0.1 Sodium saccharin 0.1 Sodium Lauryl Sulfate 1.5 Sodium Methyl Lauroyl Taurate 0.5 Isopropyl methylphenol 0.1 Pyridoxine hydrochloride 0.1 Concentrated glycerin 20 Glycerin fatty acid ester 0.5 Polyoxyethylene hydrogenated castor oil 1.0 Fragrance 1.0 Propylene glycol remainder Total 100%

[0044] It was confirmed that the above-mentioned gel dentifrice, toothpaste, liquid dentifrice, and non-aqueous dentifrice improve the retention of quaternary ammonium salts containing a benzene ring on apatite beads.

Claims

1. A bactericidal component retention promoter for promoting retention of a bactericidal component on a tooth surface, characterized in that it contains (A) a divalent metal ion source and (B) a chelating agent, wherein the bactericidal component is a quaternary ammonium salt containing a benzene ring.

2. 2. The bactericidal component retention promoter according to claim 1, wherein the divalent metal ion source (A) is a divalent metal ion source having a halogen element.

3. 3. The bactericidal component retention promoter according to claim 2, wherein the divalent metal ion source having a halogen element is stannous fluoride.

4. The bactericidal component retention promoter according to claim 1 , wherein the bactericidal component is benzalkonium chloride or benzethonium chloride.

5. The bactericidal component retention promoter according to claim 1 , wherein the chelating agent (B) is a carboxylic acid or a salt thereof.

6. The bactericidal component retention promoter according to claim 5 , wherein the carboxylic acid or its salt is gluconic acid or lactic acid.

7. The (A) divalent metal ion source is stannous fluoride, The (B) chelating agent is gluconic acid or lactic acid, and The bactericidal component retention promoter according to claim 1 , wherein the bactericidal component is benzalkonium chloride or benzethonium chloride.

8. The bactericidal component retention promoter according to claim 1, wherein the content of the (A) divalent metal ion source is A [% by mass] and the content of the (B) chelating agent is B [% by mass], and the relationship of A:B satisfies 1:0.0033 to 1:

500.

9. The bactericidal component retention promoter according to claim 1, wherein the content of the divalent metal ion source (A) is A [% by mass] and the content of the quaternary ammonium salt containing a benzene ring as the bactericidal component is C [% by mass], so that A:C satisfies a relationship of 1:0.000167 to 1:

100.

10. 10. An oral composition for promoting retention of a bactericidal component on a tooth surface, comprising (C) a quaternary ammonium salt containing a benzene ring as a bactericidal component, and the bactericidal component retention promoter according to any one of claims 1 to 9.

11. The oral composition contains the divalent metal ion source in an amount of 0.01% by mass to 3% by mass based on the total mass of the oral composition, The (B) chelating agent is contained in an amount of 0.01% by mass to 5% by mass based on the total mass of the oral cavity composition; and The oral composition according to claim 10, comprising (C) a quaternary ammonium salt containing a benzene ring in an amount of 0.0005% by mass to 1% by mass based on the total mass of the oral composition.

12. The oral composition of claim 10 which is a dentifrice, a mouthwash, or an oral moisturizer.

13. 11. The oral composition of claim 10, which is a dentifrice selected from toothpastes, gel dentifrices, and liquid dentifrices.

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