Oral composition and Anti-candida oral composition

Abstract

To provide an oral composition that exhibits superior anti-Candida activity.SOLUTION: An oral composition comprises at least one selected from the group consisting of (A) thymol and chlorothymol. The oral composition further comprises at least one selected from the group consisting of (B) sodium lauryl sulfate, zinc gluconate, propylene glycol, ethylenediaminetetraacetic acid, and their salts and hydrates.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an oral composition and an oral composition for anti-Candida use.

Background Art

[0002] Candida bacteria are present on the surface of the mucous membranes and skin of healthy individuals as resident bacteria. Representative bacterial species of Candida bacteria include Candida albicans. For example, it is known that when Candida bacteria proliferate in elderly people with reduced immune function, denture wearers, and people with dry mouth, oral candidiasis is caused as an opportunistic infection. In recent years, it has also been reported that Candida bacteria are involved in the progression of dental caries. For example, Non-Patent Document 1 describes the relationship between the growth of Candida bacteria and the growth of S. mutans.

[0003] Patent Document 1 discloses a composition that exhibits a bactericidal action against Candida bacteria.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Non-Patent Documents

[0005]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] There is a demand for an oral composition that exhibits excellent anti-Candida action.

Means for Solving the Problem

[0007] The oral composition for solving the above problems contains (A) at least one selected from the group consisting of thymol and chlorothymol, and (B) at least one selected from the group consisting of sodium lauryl sulfate, zinc gluconate, propylene glycol, ethylenediaminetetraacetic acid, its salts and hydrates, and the gist is that the content of the component (A) is 0.04% by mass or less.

[0008] In the above oral composition, the component (B) is at least one selected from the group consisting of sodium lauryl sulfate, zinc gluconate, ethylenediaminetetraacetic acid, its salts and hydrates, and the content of the component (B) is preferably 0.01% by mass or more and 0.1% by mass or less.

[0009] The oral composition for anti-candida for solving the above problems contains (A) at least one selected from the group consisting of thymol and chlorothymol, and (B) at least one selected from the group consisting of sodium lauryl sulfate, zinc gluconate, propylene glycol, ethylenediaminetetraacetic acid, its salts and hydrates, and the gist is that it contains these.

Effects of the Invention

[0010] According to the present invention, an excellent anti-candida action can be exhibited.

Modes for Carrying Out the Invention

[0011] Embodiments embodying the oral composition and the oral composition for anti-candida will be described. Hereinafter, the oral composition will be mainly described. The oral composition can be applied as an oral composition for anti-candida.

[0012] <Component (A)> The oral composition contains, as component (A), at least one selected from the group consisting of thymol and chlorothymol (6-chlorothymol).

[0013] Thymol and chlorothymol may be used as fragrances. The oral composition may contain thymol or chlorothymol alone, or may contain thymol and chlorothymol in combination.

[0014] The content of component (A) is not particularly limited, but is, for example, 0.04% by mass or less. The above content is preferably 0.0001% to 0.04% by mass, more preferably 0.001% to 0.04% by mass, and even more preferably 0.001% to 0.01% by mass.

[0015] In the oral composition, by using it in combination with component (B) described later, even when the content of component (A) is as low as 0.04% by mass or less, an anti-Candida action can be exhibited. Hereinafter, in the oral composition, the content of each component may sometimes be expressed by omitting "% by mass" as "%".

[0016] When the oral composition contains thymol as component (A), the content of the thymol is preferably particularly in the following range.

[0017] The content of thymol is preferably, for example, 0.001% to 0.04%, more preferably 0.003% to 0.04%, and even more preferably 0.003% to 0.02%.

[0018] The upper limit value or the lower limit value of the range may be, for example, 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03 or 0.04%.

[0019] ​ 〔Chlorothymol〕 When the oral composition contains chlorothymol as the component (A), the content of the chlorothymol preferably falls within the following range in particular.

[0020] The content of chlorothymol is preferably, for example, 0.0001% or more and 0.01% or less, more preferably 0.0003% or more and 0.01% or less, still more preferably 0.0003% or more and 0.007% or less, and even more preferably 0.0003% or more and 0.004% or less.

[0021] The upper limit or lower limit of the said range may be, for example, 0.0001, 0.0002, 0.0003, 0.0004, 0.0005, 0.0006, 0.0007, 0.0008, 0.0009, 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009 or 0.01%.

[0022] <Component (B)> The oral composition contains at least one selected from the group consisting of sodium lauryl sulfate, zinc gluconate, propylene glycol, ethylenediaminetetraacetic acid, its salts and hydrates as the component (B). and contains.

[0023] The oral composition may contain the above-mentioned component (B) alone or in combination of two or more kinds of component (B). Zinc gluconate may be a hydrate.

[0024] Ethylenediaminetetraacetic acid is sometimes called edetic acid or EDTA. Hereinafter, ethylenediaminetetraacetic acid may also be referred to as EDTA. EDTA is an aminocarboxylic acid-based chelating agent.

[0025] As the EDTA contained in the oral composition, it may be a salt of EDTA or a hydrate. Examples of the salt of EDTA include sodium salt, potassium salt, calcium salt, magnesium salt and the like.

[0026] Examples of the sodium salt of EDTA include disodium ethylenediaminetetraacetate (EDTA-2Na), trisodium ethylenediaminetetraacetate (EDTA-3Na), tetrasodium ethylenediaminetetraacetate (EDTA-4Na) and the like.

[0027] The oral composition may contain only one of the above various EDTA, or may contain a combination of two or more thereof. As the EDTA contained in the oral composition, it is preferably a salt of EDTA, more preferably a sodium salt of EDTA, still more preferably a sodium salt hydrate of EDTA, and particularly preferably disodium ethylenediaminetetraacetate dihydrate.

[0028] As the component (B) contained in the oral composition, it is preferably sodium lauryl sulfate, zinc gluconate, ethylenediaminetetraacetic acid, its salt and hydrate, and more preferably sodium lauryl sulfate and zinc gluconate.

[0029] The content of the component (B) is not particularly limited. For example, it is 0.01% or more and 10% or less. The above content is preferably 0.01% or more and 1% or less, and more preferably 0.01% or more and 0.1% or less.

[0030] When the oral composition contains at least one selected from the group consisting of sodium lauryl sulfate, zinc gluconate, and EDTA as the component (B), the content of the component is preferably in the following range in particular. For example, the content is preferably 0.01% or more and 0.5% or less, more preferably 0.01% or more and 0.1% or less, and even more preferably 0.01% or more and 0.05% or less. The upper limit or the lower limit of the range may be, for example, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, or 0.5%.

[0031] When the oral composition contains propylene glycol as the component (B), the content of the propylene glycol is preferably in the following range in particular. For example, the content of propylene glycol is preferably 1% or more and 10% or less, more preferably 1% or more and 8% or less, and even more preferably 1% or more and 5% or less. The upper limit or the lower limit of the range may be, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10%.

[0032] <Other components> The oral composition may contain other components other than the aforementioned components according to the application purpose, form, use, etc. Examples of the other components include surfactants, flavoring agents, sweetening agents, wetting agents, adhesives binders, preservatives, coloring agents, pH adjusters, chelating agents, medicinal components, bases, stabilizers, abrasives, and the like. As the other components, known ones blended in the oral composition can be used. The oral composition may contain only one kind of each of the above other components alone, or may contain a combination of two or more kinds.

[0033] Examples of the surfactant include nonionic surfactants, anionic surfactants, amphoteric surfactants, and cationic surfactants. Specific examples of nonionic surfactants include, for example, sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester, lactose fatty acid ester; fatty acid alkanolamides; glycerin fatty acid ester; sorbitan fatty acid ester; fatty acid monoglyceride; polyoxyethylene alkyl ether with a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group having 13 to 15 carbon atoms; polyoxyethylene alkyl phenyl ether with a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group having 9 carbon atoms; diethyl sebacate; polyoxyethylene hydrogenated castor oil; fatty acid polyoxyethylene sorbitan, etc.

[0034] Specific examples of anionic surfactants include, for example, sulfate esters such as sodium polyoxyethylene lauryl ether sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate, sodium polyoxyethylene lauryl ether sulfosuccinate; acyl amino acid salts such as sodium lauroyl methyl alanine; sodium cocoyl methyl taurine, etc.

[0035] Specific examples of amphoteric surfactants include, for example, betaine type surfactants such as lauryl dimethylaminoacetic acid betaine, coconut oil fatty acid amide propyl dimethylaminoacetic acid betaine; imidazoline type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine sodium; amino acid type surfactants such as N-lauryl diaminoethyl glycine, etc.

[0036] Specific examples of cationic surfactants include, for example, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, N-coconut oil fatty acid acyl-L-arginine ethyl·DL-pyrrolidone carboxylate, etc.

[0037] Specific examples of the fragrance agent include, for example, menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronellyl acetate, methyl eugenol, cineol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, pimento oil, d-camphor, d-borneol, star anise oil, cinnamon oil, anise oil, cinnamaldehyde, mint oil, vanillin, and the like.

[0038] Specific examples of the sweetening agent include, for example, sodium saccharin, acesulfame potassium, stevioside, neohesperidin dihydrochalcone, perillartine, thaumatin, aspartylphenylalanyl methyl ester, p-methoxycinnamic aldehyde, and the like.

[0039] Specific examples of the wetting agent include, for example, sorbitol, ethylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactitol, polyoxyethylene glycol, and the like.

[0040] Specific examples of the binder include, for example, sodium carboxymethyl cellulose, carboxy Cellulose derivatives such as methyl ethyl cellulose salts, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, crystalline cellulose, crystalline cellulose - sodium carboxymethyl cellulose, etc., microbial - produced polymers such as xanthan gum, tragacanth gum, karaya gum, gum arabic, guar gum, carrageenan, dextrin, agar, pectin, pullulan, gellan gum, locust bean gum, natural polymers or natural rubbers such as sodium alginate, synthetic polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, polyvinyl methyl ether, sodium polyacrylate, etc., thickening silica, inorganic binders such as beegum, cationic binders such as O - [2 - hydroxy - 3 - (trimethylammonio)propyl] hydroxyethyl cellulose chloride, etc. can be mentioned.

[0041] Specific examples of preservatives include, for example, parabens such as methyl paraben, ethyl paraben, propyl paraben, butyl paraben, etc., sodium benzoate, phenoxyethanol, alkyl diaminethyl glycine hydrochloride, etc.

[0042] Specific examples of colorants include, for example, legal dyes such as Blue No. 1, Yellow No. 4, Red No. 202, Green No. 3, etc., mineral - based pigments such as ultramarine, fortified ultramarine, dark ultramarine, etc., titanium oxide, etc. Specific examples of pH adjusters include, for example, citric acid, phosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or their chemically possible salts, sodium hydroxide, etc.

[0043] Specific examples of chelating agents include, for example, phytic acid, pyrophosphoric acid, polyphosphoric acid, malic acid, etc. Specific examples of the active ingredient include, for example, vitamin Es such as dl-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate; vitamin Cs such as ascorbic acid, sodium ascorbate, or magnesium ascorbyl phosphate; vitamin B6s such as pyridoxine hydrochloride; glycyrrhizinate and its derivatives, glycyrrhetinic acid, amphoteric bactericides such as dodecyldiaminoethyl glycine; nonionic bactericides such as triclosan, isopropylmethylphenol, or polyoxyethylene lauryl ether; anionic bactericides such as sodium cocoyl sarcosinate or sorbic acid; cationic bactericides such as cetylpyridinium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, benzalkonium chloride, or benzethonium chloride; enzymes such as dextranase, amylase, protease, mutanase, lysozyme, or lytic enzyme (lytech enzyme); alkali metal monofluorophosphates such as sodium monofluorophosphate or potassium monofluorophosphate; fluorides such as sodium fluoride or stannous fluoride; tranexamic acid or epsilon-aminocaproic acid; aluminum chlorhydroxyl allantoin; dihydrocholesterol; hinokitiol; sodium copper chlorophyllin; chlorophyll; sodium chloride; caropeptide; allantoin; carbazochrome; potassium nitrate; paratinit, etc.

[0044] Specific examples of the base include, for example, alcohols, silicon, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastic base, etc.

[0045] Specific examples of the alcohols include, for example, ethyl alcohol, lauryl alcohol, myristyl alcohol, etc. Specific examples of the stabilizer include, for example, sodium thiosulfate, sodium sulfite, calcium lactate, lanolin, triacetin, castor oil, magnesium sulfate, etc.

[0046] Specific examples of the abrasive include, for example, calcium carbonate, magnesium carbonate, dicalcium phosphate, tricalcium phosphate, magnesium phosphate, silica, zeolite, sodium metaphosphate, aluminum hydroxide, magnesium hydroxide, calcium pyrophosphate, benga la, calcium sulfate, anhydrous silicic acid, and the like.

[0047] <Application form, use, and dosage form> The application forms of the oral composition and the oral composition for anti-candidiasis are not particularly limited, and for example, they can be used as pharmaceuticals, quasi-drugs, and cosmetics.

[0048] As uses of the oral composition and the oral composition for anti-candidiasis, they can be used for anti-candidiasis that exerts a bactericidal action against Candida bacteria. For example, they can be used for sterilization in the oral cavity, at the corners of the mouth, dentures, etc.

[0049] Specific uses include, for example, chewing agents, orally dissolving agents, orally disintegrating agents, tongue care agents, oral cooling agents, mouthwashes, gargles, toothpastes, halitosis preventives, gum massagers, oral wetting agents, tongue coating removers, oral coatings, oral bactericides, throat bactericides, oral and throat agents, periodontal disease therapeutics, denture coatings, denture stabilizers, denture preservatives, denture cleaners, implant care agents, etc. Examples of toothpastes include paste toothpastes, powder toothpastes, liquid toothpastes, lubricating toothpastes, etc.

[0050] The oral composition and the oral composition for anti-candidiasis contain solvents such as water and alcohol. The dosage forms of the oral composition and the oral composition for anti-candidiasis are not particularly limited, and for example, they can be applied to forms (dosage forms) such as ointments, pastes, pastes, sprays, gels, solutions, suspensions, gums, tablets, drops, etc.

[0051] <Action of this embodiment> By using component (A) and component (B) in combination, a synergistic effect can exert an excellent anti-Candida action as compared with the case where component (A) or component (B) is used alone. For example, according to an oral composition containing a combination of component (A) and component (B), an anti-Candida action can be exerted even when component (A) is at a low concentration.

[0052] <Effects of the present embodiment> (1) Due to the excellent anti-Candida action, Candida bacteria can be sterilized. In addition, the growth of Candida bacteria can be suppressed. Thereby, an effect of preventing candidiasis and an effect of treating candidiasis can be expected. Further, since the growth of Candida bacteria can be suppressed, an effect of preventing dental caries can be expected.

[0053] (2) The excellent anti-Candida action is exerted even when the content of component (A) is 0.04% by mass or less. (3) In an oral composition in which component (B) is at least one selected from the group consisting of sodium lauryl sulfate, zinc gluconate, ethylenediaminetetraacetic acid, its salts and hydrates, an excellent anti-Candida action can be exerted even when component (B) is at a low concentration. Specifically, in the oral composition, an excellent anti-Candida action can be exerted even when the content of component (B) is 0.01% by mass or more and 0.1% by mass or less.

Examples

[0054] The oral composition and the anti-Candida oral composition will be described in more detail based on the following examples. Note that the oral composition and the anti-Candida oral composition are not limited to the configurations described in the examples column.

[0055] <Pre-culture of bacteria> Candida bacteria (C. albicans ATCC10231) were pre-cultured in YPD medium at 37 °C under aerobic conditions for 24 hours. The culture solution was diluted with distilled water to adjust OD 660 = 0.1.

[0056] <Measurement test of minimum growth inhibition concentration: alone> For each material shown in Table 1, the minimum inhibitory concentration (MIC) against Candida was measured by the micro - liquid dilution method. Regarding zinc gluconate, zinc gluconate n - hydrate (zinc gluconate 88%) was used. For EDTA, disodium ethylenediaminetetraacetate dihydrate was used. PG in the table means propylene glycol.

[0057] (Preparation Example 1) A material - containing solution was prepared by dissolving thymol in a 10% ethanol aqueous solution. By mixing the 2×YPD medium and the above - mentioned material - containing solution in equal amounts, a YPD medium containing the material was obtained. A dilution series was prepared by serially diluting the YPD medium containing the material.

[0058] (Preparation Example 2) A dilution series was prepared in the same manner as Preparation Example 1, except that chlorothymol was used instead of thymol.

[0059] (Preparation Example 3) A dilution series was prepared in the same manner as Preparation Example 1, except that sodium lauryl sulfate was used instead of thymol and water was used instead of the 10% ethanol aqueous solution.

[0060] (Preparation Example 4) A dilution series was prepared in the same manner as Preparation Example 3, except that zinc gluconate was used instead of sodium lauryl sulfate.

[0061] (Preparation Example 5) A YPD medium containing the material was obtained by dissolving EDTA in the YPD medium. A dilution series was prepared by serially diluting the YPD medium containing the material.

[0062] (Preparation Example 6) A dilution series was prepared in the same manner as Preparation Example 5, except that propylene glycol was used instead of EDTA.

[0063] (Test Example) After inoculating 20 μl of the above-precultured bacterial solution into 100 μl of YPD medium containing each material, the mixture was cultured at 37°C under aerobic conditions for 72 hours. The presence or absence of bacterial growth was determined by visually checking the turbidity of the medium. The minimum concentration at which no bacterial growth was confirmed is shown in Table 1 as the single MIC (mass%). For EDTA, bacterial growth was confirmed even at the maximum concentration of 1 mass%.

[0064] [Table 1] [Measurement test of minimum growth inhibitory concentration: combined use] The anti-Candida effect was evaluated when the components (A) and (B) shown in Table 2 were used in combination.

[0065] When the components (A) and (B) were used in combination, the MIC was measured by the checkerboard method. The medium, bacterial solution, and culture conditions used were the same as those in the test for measuring the single MIC above. The results are shown in Table 2 as the combined MIC (mass%).

[0066] [Evaluation of combined effect] Based on the following formula (1), the FIC (Fractional Inhibitory Concentration) index x was calculated. The results are shown in Table 2.

[0067] FIC index = A1 / A0 + B1 / B0 … (Formula 1) In formula (1), A0 represents the MIC of component (A) alone. A1 represents the MIC of component (A) when components (A) and (B) are used in combination. B0 represents the MIC of component (B) alone. B1 represents the MIC of component (B) when components (A) and (B) are used in combination. That is, A0 and B0 are the values of the single MIC shown in Table 1. A1 and B1 are the values of the combined MIC shown in Table 2.

[0068] The fact that the FIC index is less than 1 means that the effect of using components (A) and (B) in combination is significant compared to the sum of the effects when using component (A) or component (B) alone. The combined effect was evaluated according to the following criteria. Antagonistic effect: The FIC index is greater than 2. Additive effect: The FIC index is 1 or more and 2 or less. Synergistic effect: The FIC index is less than 1.

[0069] [Table 2] As shown in Table 2, when components (A) and (B) are used in combination, the FIC index is less than 1 for any combination. It was confirmed that a synergistic effect can be obtained by using components (A) and (B) in combination.

[0070] <Examples> As oral compositions, Examples 1 to 17 shown in Table 3 were prepared. The numerical values shown in Table 3 mean mass%. For each example, the balance is a 1% aqueous ethanol solution.

[0071] In Examples 1 to 17, the contents of component (A) and component (B) are each equal to or higher than the combined MIC. Therefore, it can be seen that in any of the examples, by using component (A) and component (B) in combination, an excellent anti-Candida effect is exhibited due to the synergistic effect. It can be seen that by using component (A) and component (B) in combination, an excellent anti-Candida effect is exhibited even at a low concentration where the content of component (A) is 0.04 mass% or less.

[0072] [Table 3]

Claims

1. at least one selected from the group consisting of thymol and chlorothymol, and at least one selected from the group consisting of sodium lauryl sulfate, zinc gluconate, propylene glycol, ethylenediaminetetraacetic acid, its salts and hydrates, wherein the content of the component (A) is 0.04% by mass or less oral composition.

2. wherein the component (B) is at least one selected from the group consisting of sodium lauryl sulfate, zinc gluconate, ethylenediaminetetraacetic acid, its salts and hydrates, and the content of the component (B) is 0.01% by mass or more and 0.1% by mass or less The oral composition according to Claim 1.

3. at least one selected from the group consisting of thymol and chlorothymol, and at least one selected from the group consisting of sodium lauryl sulfate, zinc gluconate, propylene glycol, ethylenediaminetetraacetic acid, its salts and hydrates, oral composition for anti - Candida.

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