Bactericidal agent for penetration into deep layer of dental plaque

Abstract

To provide a bactericidal agent for penetration into the deep layer of dental plaque that allows a bactericidal component to penetrate from the surface layer to the inner deep layer of dental plaque.SOLUTION: Provided is a bactericidal agent for penetration into the deep layer of dental plaque that comprises glycyrrhetinic acid (X) and a cationic bactericidal agent (Y) as active ingredients.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to antiseptic agents for penetrating deep layers of dental plaque. [Background technology]

[0002] It is known that dental plaque, which is a bacterial mass, is formed in the oral cavity by exopolysaccharides (EPS) produced by bacteria. Since dental plaque has an anaerobic environment from the surface to the deeper layers, the number of anaerobic bacteria tends to increase in the deeper layers of the plaque. Therefore, the inventors have noticed that in order to reduce the number of bacteria in the oral cavity, it is very effective to allow a bactericide to fully penetrate into the deeper layers of the plaque and exert its effect. On the other hand, it has been reported that cationic bactericides, which are often used as ingredients with strong bactericidal activity, are ingredients that do not easily penetrate into the deep layers of dental plaque (see Non-Patent Document 1).

[0003] In this context, various agents and compositions have been developed for application to the oral cavity that contain glycyrrhetinic acid, which exerts pharmacological effects such as anti-inflammatory and alveolar bone resorption inhibitory effects, and each of these exerts the desired effects. For example, Patent Document 1 discloses an oral composition that uses a specific amount of a higher alcohol, a fatty acid or its salt, and a surfactant together with an oil-soluble medicinal ingredient such as glycyrrhetinic acid, thereby increasing the amount of the oil-soluble medicinal ingredient adsorbed to the gums and oral mucosa. In addition, Patent Document 2 discloses an oral flora improving agent containing β-glycyrrhetinic acid as an agent or composition for various improvements, and Patent Document 3 discloses an oral composition that includes a taste improving agent containing β-glycyrrhetinic acid or the like as an active ingredient. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2017-214319 A [Patent Document 2] JP 2022-163809 A [Patent Document 3] JP 2023-5021 A [Non-patent literature]

[0005] [Non-Patent Document 1] Journal of Applied Microbiology,2005,V.99,p.703‐715 Summary of the Invention [Problem to be solved by the invention]

[0006] Thus, although various attempts have been made using glycyrrhetinic acid in the above-mentioned patent documents, no attempt has been made to sufficiently penetrate a bactericidal component into dental plaque using such glycyrrhetinic acid.

[0007] Therefore, the present invention relates to a bactericidal agent capable of penetrating deep layers of dental plaque, which is capable of penetrating a bactericidal component from the surface layer of dental plaque to the deep inner layer. [Means for solving the problem]

[0008] Therefore, the present inventors have conducted extensive research to solve the above problems, and have found that by using glycyrrhetinic acid (X) and a cationic bactericide (Y) as active ingredients, it is possible to obtain an agent that can effectively promote the penetration of the cationic bactericide from the surface layer of plaque that is firmly attached to the tooth surface, between the teeth, etc., to the deeper layers inside the plaque.

[0009] That is, the present invention provides a bactericide capable of penetrating deep into dental plaque, which contains glycyrrhetinic acid (X) and a cationic bactericide (Y) as active ingredients. Effect of the Invention

[0010] According to the bactericide of the present invention for penetrating deep layers of dental plaque, a cationic bactericide which is considered to have difficulty penetrating deep layers of dental plaque can be sufficiently penetrated not only into the surface layer of dental plaque that is firmly attached to the tooth surface and between the teeth, but also into the deep inner layers, thereby effectively enhancing the bactericidal action throughout the entire dental plaque area. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The present invention will be described in detail below. In the present invention, the term "deep layer of dental plaque" refers to the part of dental plaque that is located deep inside the dental plaque that is firmly attached to the tooth surface, between the teeth, etc.

[0012] The disinfectant for penetrating deep layers of dental plaque of the present invention contains glycyrrhetinic acid (X) as an active ingredient. Glycyrrhetinic acid (X) is an ingredient obtained by hydrolyzing glycyrrhizinic acid obtained from licorice etc. Glycyrrhetinic acid (X) is known to have anti-inflammatory effects, alveolar bone resorption inhibitory effects, histamine release inhibitory effects, etc. However, the present inventors have unexpectedly discovered that glycyrrhetinic acid (X) selectively acts on cationic bactericide (Y) among various bactericides, effectively promoting the penetration into the interior of dental plaque, thereby enabling the cationic bactericide (Y), which was previously thought to have difficulty penetrating into the deep layers of dental plaque, to sufficiently penetrate into the deep layers of dental plaque.

[0013] The disinfectant for penetrating deep layers of dental plaque of the present invention contains a cationic disinfectant (Y) as an active ingredient. The penetration of the cationic disinfectant (Y) into deep layers of dental plaque is effectively promoted by the glycyrrhetinic acid (X), and the disinfectant action can be enhanced throughout the entire dental plaque area from the surface layer to the deep layers.

[0014] Specific examples of the cationic bactericide (Y) include one or more compounds selected from quaternary ammonium compounds and biguanide compounds. Cationic disinfectants belonging to the quaternary ammonium compounds include one or more selected from cetylpyridinium chloride, benzethonium chloride, decapotassium chloride, benzalkonium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, and methylbenzethonium chloride. Cationic disinfectants belonging to the biguanide compound include one or more selected from chlorhexidine and its salts such as chlorhexidine gluconate and chlorhexidine hydrochloride.

[0015] In the bactericide of the present invention for penetrating deep layers of dental plaque, the mass ratio ((X):(Y)) of the content of glycyrrhetinic acid (X) to the content of cationic bactericide (Y) is, from the viewpoint of effectively promoting the penetration of the cationic bactericide (Y) into deep layers of dental plaque by glycyrrhetinic acid (X), preferably 1:0.01 to 1:50, more preferably 1:0.03 to 1:40, even more preferably 1:0.05 to 1:35, and even more preferably 1:1 to 1:10.

[0016] The formulation of the bactericide for penetrating deep layers of dental plaque of the present invention may be a gel, paste or gel formulation such as toothpaste, powdered toothpaste, or gel-type toothpaste, which is filled into a tube container or a pump container and discharged when used, or a liquid formulation such as a liquid mouthwash or liquid toothpaste. It may also be a liquid formulation such as a liquid for a foam-discharging container, which is filled into a foam-discharging container and discharged in foam form from a discharge port when used. When the bactericide for penetrating deep layers of dental plaque of the present invention takes these formulations, it may be in the form of a single formulation or a two-formulation. Hereinafter, these dosage forms will be collectively referred to as "dentifrices, etc."

[0017] When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a single-component formulation such as a dentifrice, both glycyrrhetinic acid (X) and the cationic bactericide (Y) are contained in the single agent, and therefore when applied to the oral cavity, glycyrrhetinic acid (X) and the cationic bactericide (Y) can act on dental plaque together, enabling a simple and labor-saving usage mode.

[0018] When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a single-component formulation such as a dentifrice, the content of glycyrrhetinic acid (X) in the bactericide for penetrating deep layers of dental plaque of the present invention is, from the viewpoint of effectively promoting the penetration of the cationic bactericide (Y) into deep layers of dental plaque, preferably 0.0005% by mass or more, more preferably 0.001% by mass or more, even more preferably 0.0012% by mass or more, preferably 0.5% by mass or less, more preferably 0.3% by mass or less, even more preferably 0.2% by mass or less, even more preferably 0.08% by mass or less, and even more preferably 0.01% by mass or less. When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a one-component formulation such as a dentifrice, the content of glycyrrhetinic acid (X) in the bactericide for penetrating deep layers of dental plaque of the present invention is preferably 0.0005 to 0.5% by mass, more preferably 0.001 to 0.3% by mass, even more preferably 0.0012 to 0.2% by mass, still more preferably 0.0012 to 0.08% by mass, and even more preferably 0.0012 to 0.01% by mass.

[0019] When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a one-component formulation such as a dentifrice, the content of the cationic bactericide (Y) is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, preferably 0.2% by mass or less, more preferably 0.1% by mass or less, and even more preferably 0.05% by mass or less, in order to effectively bring about a bactericidal effect in the deep layers of dental plaque. When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a one-component formulation such as a dentifrice, the content of the cationic bactericide (Y) is preferably 0.001 to 0.2% by mass, more preferably 0.005 to 0.1% by mass, and even more preferably 0.01 to 0.05% by mass, in the bactericide for penetrating deep layers of dental plaque of the present invention.

[0020] When the formulation of the bactericide for penetration into the deep layer of dental plaque of the present invention is a one-component formulation such as a dentifrice, water may be contained in addition to glycyrrhetinic acid (X) and cationic bactericide (Y) in order to allow the glycyrrhetinic acid (X) and cationic bactericide (Y) to be well diffused when applied to the oral cavity. The content of such water in the bactericide for penetration into the deep layer of dental plaque of the present invention is preferably 5% by mass or more, more preferably 10% by mass or more, even more preferably 13% by mass or more, preferably 99.9% by mass or less, more preferably 99.7% by mass or less, and even more preferably 99.5% by mass.

[0021] In particular, when the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a dentifrice such as powdered dentifrice, and is in the form of a single-component formulation, the water content in the bactericide for penetrating deep layers of dental plaque of the present invention is preferably 5% by mass or more, more preferably 10% by mass or more, even more preferably 13% by mass or more, preferably 50% by mass or less, more preferably 30% by mass or less, and even more preferably 20% by mass or less. Furthermore, when the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a liquid preparation such as a mouthwash, liquid dentifrice, or a liquid preparation for filling a foam-dispensing container, and is in the form of a one-component system, the water content in the bactericide for penetrating deep layers of dental plaque of the present invention is preferably 60% by mass or more, more preferably 65% ​​by mass or more, even more preferably 70% by mass or more, preferably 99.9% by mass or less, more preferably 99.7% by mass or less, and even more preferably 99.5% by mass or less.

[0022] When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a single-component formulation such as a dentifrice, it may contain ingredients other than those mentioned above as long as they do not impair the effects of the present invention. Specific examples of such components include one or more nonionic surfactants selected from polyoxyethylene hydrogenated castor oil; sucrose fatty acid esters; sorbitan fatty acid esters; glycerin fatty acid esters such as monoglycerin stearate, decaglycerin monostearate, pentaglycerin monomyristate, and the like; alkyl glucosides; polyoxyethylene monoalkyl (or alkenyl) ethers, polyoxyethylene polyoxypropylene copolymers, and the like; polyoxyethylene alkyl phenyl ethers, such as polyoxyethylene nonylphenyl ether, and the like; amine oxide surfactants; fatty acid alkanolamides, such as mono-(or di-)ethanolamide, coconut oil fatty acid diethanolamide, and the like; polyglycerin fatty acid esters, such as decaglyceryl laurate, and the like; and polyglycols, such as polyethylene polypropylene glycol, and the like; one or more amphoteric surfactants selected from acetate betaines such as lauryl dimethylamino acetate betaine, imidazolinium betaines such as 2-alkyl-N-carboxymethyl-N-hydroxyethyl-N-imidazolium betaine, alkyl sulfobetaines such as lauryl sulfobetaine and lauryl hydroxysulfobetaine, coconut oil fatty acid amido alkyl betaines such as coconut oil fatty acid amidopropyl betaine, and long-chain alkyl imidazoline betaine salts such as alkyl-1-hydroxyethyl imidazoline betaine sodium; one or more sugar alcohols selected from sorbitol, xylitol, erythritol, reduced palatinose, mannitol, and the like; a humectant selected from propylene glycol, 1,3-butylene glycol, polyethylene glycol, and dipropylene glycol; Binding agents such as sodium alginate, sodium carboxymethylcellulose, carrageenan, xanthan gum, sodium polyacrylate, hydroxyethylcellulose, hydroxypropylcellulose, pectin, tragacanth gum, gum arabic, guar gum, karaya gum, locust bean gum, gellan gum, tamarind gum, psyllium seed gum, polyvinyl alcohol, sodium chondroitin sulfate, and methoxyethylene maleic anhydride copolymer; abrasives such as abrasive silica (having an oil absorption of 50 to 150 mL / 100 g, the oil absorption being a value measured according to a method conforming to JIS K5101-13-2 (established in 2004)); Viscosifying silica (oil absorption measured according to the method of JIS K5101-13-2 (established in 2004) is 200 to 400 mL / 100 g); Examples of the additives include foaming assistants; preservatives such as isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, and ethyl parahydroxybenzoate; pH adjusters such as sodium hydroxide; pigments; coloring materials; and fragrances.

[0023] When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a dentifrice or the like in the form of a two-component system, one of the components may be a component containing glycyrrhetinic acid (X) and the other a component containing cationic bactericide (Y). By making it a two-component system, it is possible to apply the two components one by one to the oral cavity in sequence. From the viewpoint of further enhancing the penetrating effect of the cationic bactericide (Y) into the deep layers of dental plaque, it is preferable to apply the cationic bactericide (Y) after applying the glycyrrhetinic acid (X) as the active ingredient. Specifically, first, an agent containing glycyrrhetinic acid (X) is applied to the oral cavity, and then an agent containing a cationic bactericide (Y) is applied to the oral cavity.

[0024] Even when the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a two-component formulation such as a dentifrice, it is preferable to prepare each agent so that the mass ratio ((X):(Y)) of the content of glycyrrhetinic acid (X) to the content of cationic bactericide (Y) is the above-mentioned value, assuming that the agent containing glycyrrhetinic acid (X) and the agent containing cationic bactericide (Y) are applied in equal amounts.

[0025] Specifically, for example, when the formulation of the bactericide for penetration into the deep layers of dental plaque of the present invention is a dentifrice or the like, and is in the form of a two-component formulation of a glycyrrhetinic acid (X)-containing agent and a cationic bactericide (Y)-containing agent, the content of glycyrrhetinic acid (X) in the glycyrrhetinic acid (X)-containing agent is preferably 0.0005% by mass or more, more preferably 0.001% by mass or more, even more preferably 0.0012% by mass or more, preferably 0.5% by mass or less, more preferably 0.3% by mass or less, even more preferably 0.2% by mass or less, even more preferably 0.08% by mass or less, and even more preferably 0.01% by mass or less, in terms of effectively enhancing the penetration-promoting effect of the cationic bactericide (Y) applied subsequently into the deep layers of dental plaque. When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a dentifrice or the like and is in the form of a two-component formulation of an agent containing glycyrrhetinic acid (X) and an agent containing a cationic bactericide (Y), the content of glycyrrhetinic acid (X) in the agent containing glycyrrhetinic acid (X) is preferably 0.0005 to 0.5% by mass, more preferably 0.001 to 0.3% by mass, even more preferably 0.0012 to 0.2% by mass, even more preferably 0.0012 to 0.08% by mass, and still more preferably 0.0012 to 0.01% by mass.

[0026] When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a dentifrice or the like, and is in the form of a two-component formulation of an agent containing glycyrrhetinic acid (X) and an agent containing a cationic bactericide (Y), the content of the cationic bactericide (Y) in the agent containing cationic bactericide (Y) is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, and preferably 0.2% by mass or less, more preferably 0.1% by mass or less, and even more preferably 0.05% by mass or less, from the viewpoint of fully exerting the penetration-promoting effect of the glycyrrhetinic acid (X) previously applied. When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a dentifrice or the like and is in the form of a two-component formulation of an agent containing glycyrrhetinic acid (X) and an agent containing a cationic bactericide (Y), the content of the cationic bactericide (Y) in the agent containing cationic bactericide (Y) is preferably 0.001 to 0.2 mass%, more preferably 0.005 to 0.1 mass%, and even more preferably 0.01 to 0.05 mass%.

[0027] Even when the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a two-component formulation such as a dentifrice, it may contain water, just as when the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a single-component formulation such as a dentifrice, and the content of water is also the same as when the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a single-component formulation. Furthermore, even when the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a two-component formulation such as a dentifrice, the bactericide may contain the above-mentioned components other than glycyrrhetinic acid (X) and the cationic bactericide (Y) as appropriate, as in the case where the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a single-component formulation such as a dentifrice, within the scope of not impairing the effects of the present invention.

[0028] The formulation of the bactericide for penetrating deep layers of dental plaque of the present invention may be in the form of a dentifrice or the like, or may be in the form of a sheet that is applied to teeth or the area around teeth in the oral cavity (hereinafter also referred to as "teeth, etc."). When the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a sheet, the layer structure of the sheet may have a layer containing both glycyrrhetinic acid (X) and cationic bactericide (Y) as at least a layer having a surface to be applied to teeth, etc. In this case, by simply applying the sheet to teeth, etc. in the oral cavity, glycyrrhetinic acid (X) and cationic bactericide (Y) can be made to act on dental plaque all at once, as in the case where the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a single agent such as the above-mentioned dentifrice, and a simple and time-saving usage mode is possible. The area around the teeth refers to organs in the oral cavity located around the teeth, including the gums.

[0029] Alternatively, when the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a sheet, it may have a layer structure having a layer containing glycyrrhetinic acid (X) and a layer containing a cationic bactericide (Y) as separate layers, with either layer having a surface to be attached to teeth, etc. In this case, similar to the case when the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is a two-component form such as a dentifrice, it is possible to sequentially apply a layer containing glycyrrhetinic acid (X) and a layer containing a cationic bactericide (Y) one by one, i.e., glycyrrhetinic acid (X) and cationic bactericide (Y) sequentially to the oral cavity.

[0030] In the case of such a sheet-like dosage form, when a layer containing glycyrrhetinic acid (X) and a layer containing cationic bactericide (Y) are formed as separate layers, specifically, as described above, from the viewpoint of further enhancing the penetration effect of the cationic bactericide (Y) into the deeper layers of dental plaque, it is preferable to apply glycyrrhetinic acid (X) first and then apply the cationic bactericide (Y). Therefore, it is preferable to form a layer structure having a layer containing glycyrrhetinic acid (X) as the layer having the surface to be attached to teeth, etc., and an outer layer containing a cationic bactericide (Y). Even when the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a sheet, the mass ratio ((X):(Y)) of the content of glycyrrhetinic acid (X) to the content of cationic bactericide (Y) may be controlled within the same range as above.

[0031] When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a sheet, the mass of glycyrrhetinic acid (X) is adjusted to the unit area (1 cm2) of the bactericide for penetrating deep layers of dental plaque of the present invention from the viewpoint of effectively promoting the penetration of the cationic bactericide (Y) into the deep layers of dental plaque. 2 ), preferably 0.01 mg / cm 2 More preferably, it is 0.02 mg / cm or more. 2 More preferably, it is 0.03 mg / cm 2 or more, preferably 0.1 mg / cm 2 More preferably, it is 0.08 mg / cm or less. 2 More preferably, it is 0.07 mg / cm or less. 2 When the formulation of the germicide for penetrating deep layers of dental plaque of the present invention is in the form of a sheet, the content of glycyrrhetinic acid (X) is determined based on the unit area (1 cm 2 ), preferably 0.01 to 0.1 mg / cm 2 and more preferably 0.02 to 0.08 mg / cm 2 and more preferably 0.03 to 0.07 mg / cm 2 It is.

[0032] When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a sheet, the mass of the cationic bactericide (Y) is set to 1 / 100 the mass per unit area (1 cm2) of the bactericide for penetrating deep layers of dental plaque of the present invention, from the viewpoint of effectively exerting a bactericidal effect on the deep layers of dental plaque. 2 ), preferably 0.00005 mg / cm 2 More preferably, it is 0.0001 mg / cm or more. 2 More preferably, it is 0.0003 mg / cm 2 or more, preferably 0.1 mg / cm 2 More preferably, it is 0.05 mg / cm or less.2 More preferably, it is 0.03 mg / cm or less. 2 When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a sheet, the content of the cationic bactericide (Y) is determined based on the unit area (1 cm 2 ), preferably 0.00005 to 0.1 mg / cm 2 and more preferably 0.0001 to 0.05 mg / cm 2 and more preferably 0.0003 to 0.03 mg / cm 2 It is.

[0033] When the formulation of the bactericide for penetration into the deep layer of dental plaque of the present invention is in the form of a sheet, it may contain water in addition to glycyrrhetinic acid (X) and cationic bactericide (Y) from the viewpoint of ensuring good diffusibility in the oral cavity while dissolving or dispersing glycyrrhetinic acid (X) and cationic bactericide (Y) well when applied to teeth, etc. The content of such water is preferably 3% by mass or more, more preferably 6% by mass or more, even more preferably 9% by mass or more, and preferably 20% by mass or less, more preferably 15% by mass or less, and even more preferably 10% by mass or less, as the total moisture content in the bactericide sheet for penetration into the deep layer of dental plaque of the present invention.

[0034] When the disinfectant for penetrating deep layers of dental plaque of the present invention is in the form of a sheet, ingredients other than the above-mentioned ingredients may be contained within the range that does not impair the effect of the present invention. Specific examples of such ingredients include water-soluble polymers such as pullulan, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, guar gum, gelatin, tamarind gum, pectin, gum arabic, xanthan gum, tragacanth gum, locust bean gum, dextrin, dextran, agar, starch, carboxymethyl cellulose, methyl cellulose, and hydroxyethyl cellulose, as well as the above-mentioned nonionic surfactants and other surfactants; preservatives such as isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, and ethyl parahydroxybenzoate; pH adjusters such as sodium hydroxide; pigments; colorants; and fragrances, as in the case where the formulation of the bactericide for penetrating deep layers of plaque of the present invention is a dentifrice, etc.

[0035] Alternatively, when the formulation of the bactericide of the present invention for penetrating into deep layers of dental plaque is in the form of a sheet and has a layer structure in which the layer having a surface to be attached to teeth or the like is a layer containing glycyrrhetinic acid (X) and the outer layer is a layer containing a cationic bactericide (Y), from the viewpoint of applying glycyrrhetinic acid (X) in advance and then applying the cationic bactericide (Y) later, the solubility in saliva of the layer containing glycyrrhetinic acid (X) is preferably lower than the solubility in saliva of the layer containing cationic bactericide (Y), from the viewpoint of further enhancing the penetrating effect of the cationic bactericide (Y) into deep layers of dental plaque. In this case, the layer containing glycyrrhetinic acid (X) preferably contains one or more water-insoluble polymers selected from ethyl cellulose, hydroxypropyl methylcellulose acetate succinate, cellulose acetate phthalate, hypromellose phthalate, shellac, polyvinyl acetate, polymethyl methacrylate, methacryloylethyl betaine / methacrylate copolymer, methacrylic acid copolymer, aminoalkyl methacrylate copolymer, and agar. Among these, from the viewpoints of ensuring good flexibility of the sheet and reducing discomfort during application to teeth, etc., one or two selected from ethyl cellulose and shellac are preferred, and ethyl cellulose is more preferred.

[0036] When the formulation of the bactericide for penetrating deep layers of dental plaque of the present invention is in the form of a sheet, the total thickness of the sheet is preferably 35 to 500 μm, more preferably 50 to 150 μm, and even more preferably 60 to 70 μm, from the viewpoint of dissolving in saliva over an appropriate period of time and allowing the glycyrrhetinic acid (X) and the cationic bactericide (Y) to act effectively.

[0037] When the formulation of the bactericide of the present invention for penetrating deep layers of dental plaque is in the form of a sheet, in addition to the layer containing both glycyrrhetinic acid (X) and the cationic bactericide (Y), or the layer containing glycyrrhetinic acid (X) and the layer containing the cationic bactericide (Y), an adhesive layer or an intermediate layer may be provided as necessary.

[0038] The use of the bactericide of the present invention for penetrating deep layers of dental plaque is also highly useful as a method for penetrating the cationic bactericide (Y) deep into the layers of dental plaque. From the viewpoint of further enhancing the penetration effect of the cationic bactericide (Y) into the deep layer of dental plaque, it is preferable to apply the cationic bactericide (Y) to the oral cavity after applying the glycyrrhetinic acid (X) to the oral cavity. Specifically, it is preferable to apply the cationic bactericide (Y) to the oral cavity after applying the glycyrrhetinic acid (X) to the oral cavity, preferably 5 seconds or more, more preferably 10 seconds or more, even more preferably 30 seconds or more, preferably 15 minutes or less, more preferably 10 minutes or less, and even more preferably 5 minutes or less. It is preferable to apply the cationic bactericide (Y) to the oral cavity after applying the glycyrrhetinic acid (X) to the oral cavity, preferably 5 seconds or more and 15 minutes or less, more preferably 10 seconds to 10 minutes, and even more preferably 30 seconds to 5 minutes. In addition, when using a bactericide for penetrating deep layers of dental plaque, which is in the form of a two-component formulation such as a dentifrice, an agent containing glycyrrhetinic acid (X) may be applied to the oral cavity, and then an agent containing a cationic bactericide (Y) may be applied to the oral cavity after the above-mentioned time has elapsed. In addition, when a bactericide for penetrating deep layers of dental plaque is used, the formulation is in the form of a sheet, the surface to be attached to teeth, etc. is a layer containing glycyrrhetinic acid (X), and the outer layer thereof is a layer containing a cationic bactericide (Y), the sheet may be designed so that after the layer containing glycyrrhetinic acid (X) is attached to teeth, etc., the layer containing cationic bactericide (Y) is dissolved by saliva when the above-mentioned time has elapsed, and can act in the oral cavity.

[0039] In addition, the amount of glycyrrhetinic acid (X) applied to the oral cavity is preferably 0.0005 mg or more, more preferably 0.003 mg or more, even more preferably 0.0016 mg or more, preferably 50 mg or less, more preferably 30 mg or less, and even more preferably 20 mg or less per application, from the viewpoint of further enhancing the penetration effect of the cationic bactericide (Y) into the deep layers of dental plaque. The amount of glycyrrhetinic acid (X) applied to the oral cavity is preferably 0.0005 mg or more and 50 mg or less, more preferably 0.003 to 30 mg, and even more preferably 0.0016 to 20 mg per application.

[0040] The amount of cationic bactericide (Y) applied to the oral cavity is preferably 0.003 mg or more, more preferably 0.005 mg or more, even more preferably 0.01 mg or more, preferably 20 mg or less, more preferably 10 mg or less, and even more preferably 5 mg or less per application, from the viewpoint of enhancing the bactericidal action over the entire area of ​​the plaque by penetrating not only the surface layer of the plaque but also the deep inner layer while fully enjoying the penetrating effect of glycyrrhetinic acid (X) into the deep layers of the plaque. The amount of cationic bactericide (Y) applied to the oral cavity is preferably 0.003 mg or more and 20 mg or less, more preferably 0.005 to 10 mg, and even more preferably 0.01 to 5 mg per application. EXAMPLES

[0041] The present invention will now be described in detail with reference to the following examples. In the tables, the content of each component is expressed as mass % unless otherwise specified.

[0042] Evaluation of fungicide penetration 1) Formation of dental plaque model Streptococcus mutans (JCM5705), Streptococcus gordonii (DL1), and Actinomyces naeslundii (JCM8353) were mixed, and the resulting bacterial liquid was filtered through a syringe filter (disposable membrane filter unit DISMIC 25CS (ADVANTEC)), and the filtrate was removed. The medium was prepared by adding 1.0% glucose and 2.0% sucrose to TSB-YE medium made by mixing Tryoticase Soy Broth (Difco) with 0.5% yeast extract. The membrane filter after removing the filtrate was filled with the medium and cultured anaerobically for 24 hours to form a dental plaque model formed by these three types of bacteria on the membrane filter.

[0043] 2) Exposure to test liquid Test solutions A to B were prepared according to the formulations shown in Table 1 below. Next, each of the obtained test solutions was exposed for 5 minutes to the membrane filter on which the dental plaque model had been formed in 1) above, and then anaerobically cultured for 6 hours in TSB-YE medium.

[0044] [Table 1]

[0045] 3) Quantitative determination of fungicides A bactericide test solution X having the formulation shown in Table 2 below was filtered through each membrane filter obtained in 2) above, and the final filtrate was collected.

[0046] [Table 2]

[0047] Using each of the obtained final filtrates, the concentration (mass%) of the disinfectant (cetylpyridinium chloride) in the final filtrate was quantified by high performance liquid chromatography (HPLC) using the absolute calibration curve method. Separately, the concentration (mass%) of the bactericide (cetylpyridinium chloride) in the filtrate obtained by filtration through a membrane filter on which a plaque model had not been formed was quantified and used as a reference concentration X. When this was set to 1, the ratio of the concentration (mass%) of the bactericide (cetylpyridinium chloride) in each of the final filtrates quantified above was calculated and used as an index of evaluation. The results are shown in Table 3.

[0048] [Table 3]

Claims

1. A bactericide for penetrating deep into dental plaque, comprising glycyrrhetinic acid (X) and a cationic bactericide (Y) as active ingredients.

2. The bactericide for penetrating deep layers of dental plaque according to claim 1, wherein the mass ratio ((X):(Y)) of the content of glycyrrhetinic acid (X) to the content of the cationic bactericide (Y) is 1:0.01 to 1:

50.

3. 3. The bactericide for penetrating deep layers of dental plaque according to claim 1 or 2, wherein the cationic bactericide (Y) is one or more selected from the group consisting of quaternary ammonium compounds and biguanide compounds.

4. The bactericide for penetrating deep layers of dental plaque according to any one of claims 1 to 3, wherein the content of glycyrrhetinic acid (X) is 0.0005% by mass or more and 0.5% by mass or less.

5. A method for penetrating a bactericide into the deep layers of dental plaque by applying glycyrrhetinic acid (X) and a cationic bactericide (Y) into the oral cavity.

6. 6. The method for penetrating a bactericide into a deep layer of dental plaque according to claim 5, wherein the cationic bactericide is penetrated into a deep layer of dental plaque.

7. A method for penetrating a bactericide into a deep layer of dental plaque, comprising applying glycyrrhetinic acid (X) into the oral cavity and then applying a cationic bactericide (Y) into the oral cavity.

8. 8. The method for penetrating a bactericide into a deep layer of dental plaque according to claim 7, wherein the cationic bactericide (Y) is applied into the oral cavity at a time point 5 seconds to 15 minutes after the application of glycyrrhetinic acid (X) into the oral cavity.

9. 9. The method for penetrating a bactericide into a deep layer of dental plaque according to claim 7 or 8, wherein the amount of glycyrrhetinic acid (X) applied to the oral cavity is 0.0005 mg or more and 50 mg or less per application.

10. 10. The method for penetrating a bactericide into deep layers of dental plaque according to any one of claims 7 to 9, wherein the amount of the cationic bactericide (Y) applied to the oral cavity is 0.003 mg or more and 20 mg or less per application.

11. An oral composition for penetrating a bactericide into the deeper layers of dental plaque, comprising glycyrrhetinic acid (X) and a cationic bactericide (Y).

Images