Oral composition and protease activity inhibitor

Abstract

To provide an oral composition suitable for prevention of periodontitis.SOLUTION: An oral composition contains (A) cetylpyridinium chloride hydrate, (B) at least one selected from the group consisting of ethylenediamine tetraacetic acid and salts thereof, and (C) at least one selected from the group consisting of citric acid hydrate, anhydrous citric acid and citrate. The content of component (B) is 0.0125 mass% or more. The content of component (C) is 0.2 mass% or more in terms of citric acid.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an oral composition and a protease activity inhibitor. [Background technology]

[0002] As disclosed in Patent Document 1, Porphyromonas gingivalis (hereinafter referred to as "gingivalis") is known as a bacterium associated with periodontal disease. Porphyromonas gingivalis produces gingipain, a type of protease. It has been found that the protease activity of gingipain causes the onset and progression of periodontal disease. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent Publication No. 2021-31399 Summary of the Invention [Problem to be solved by the invention]

[0004] It is believed that inhibiting the protease activity of gingipain will lead to the prevention of periodontal disease and the suppression of the progression of periodontal disease. There is a demand for an oral composition and a protease activity inhibitor that can inhibit the protease activity of gingipain. [Means for solving the problem]

[0005] The oral composition for solving the above problems comprises (A) cetylpyridinium chloride hydrate, (B) at least one selected from the group consisting of ethylenediaminetetraacetic acid and its salts, and (C) at least one selected from the group consisting of citric acid hydrate, anhydrous citric acid, and citrate salts, wherein the content of the (B) component is 0.0125% by mass or more, and the content of the (C) component is 0.2% by mass or more, calculated as citric acid.

[0006] The oral cavity composition preferably contains the component (A) in an amount of 0.05% by mass or more. An example of the oral composition is for preventing periodontal disease.

[0007] The protease activity inhibitor for solving the above-mentioned problems comprises (A) cetylpyridinium chloride hydrate, (B) at least one selected from the group consisting of ethylenediaminetetraacetic acid and salts thereof, and (C) at least one selected from the group consisting of citric acid hydrate, anhydrous citric acid, and citrate salts, wherein the content of the (B) component is 0.0125% by mass or more, and the content of the (C) component is 0.2% by mass or more, calculated as citric acid.

[0008] An example of the protease activity inhibitor inhibits the protease activity of gingipain. Effect of the Invention

[0009] The oral cavity composition and protease activity inhibitor of the present invention can exhibit an excellent effect of inhibiting the protease activity of gingipain. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 shows microscopic photographs of collagen discs when each composition was added. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] Hereinafter, one embodiment of the oral composition and the protease activity inhibitor will be described. The oral composition of this embodiment contains (A) cetylpyridinium chloride hydrate. The oral composition contains (B) at least one selected from the group consisting of ethylenediaminetetraacetic acid and its salts. The oral composition contains (C) at least one selected from the group consisting of citric acid hydrate, anhydrous citric acid, and citrate salts. The oral composition is, for example, for preventing periodontal disease.

[0012] The protease activity inhibitor of the present embodiment contains the same components as those in the oral composition described above. The components contained in the oral composition and the protease activity inhibitor will be described below. The oral composition and the protease activity inhibitor contain similar components, so the oral composition will be described below. In this specification, the oral composition means a composition intended to be used mainly in the oral cavity. It includes not only oral preparations that are discharged from the oral cavity after use, but also ingestible foods and beverages. The protease activity inhibitor is not limited to those intended to be used in the oral cavity.

[0013] <Component (A): Cecilpyridinium chloride hydrate> Cetylpyridinium chloride hydrate is also called cetypyridinium chloride or CPC. In the following, cetylpyridinium chloride hydrate is also called CPC.

[0014] CPC is generally used as a cationic bactericide. There is no particular limitation on the CPC, and any known CPC can be used. The content of CPC is not particularly limited, but is, for example, 0.005% by mass or more and 0.3% by mass or less. Hereinafter, the content of each component in the oral composition will be expressed by abbreviating "%" to "%" instead of "% by mass". The lower limit of the content of CPC is preferably 0.01%, more preferably 0.05%. The upper limit of the content of CPC is preferably 0.2%, more preferably 0.1%. The upper limit or lower limit of the range may be, for example, 0.006, 0.007, 0.008, 0.009, 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, or 0.25%.

[0015] <Component (B): Ethylenediaminetetraacetic acid> Ethylenediaminetetraacetic acid is sometimes called edetic acid or EDTA. Hereinafter, ethylenediaminetetraacetic acid is sometimes called EDTA. EDTA is an aminocarboxylic acid chelating agent. The component (B) contained in the oral composition may be a salt or a hydrate of EDTA. Examples of EDTA salts include sodium salts such as disodium ethylenediaminetetraacetate, potassium salts, and calcium salts.

[0016] The content of EDTA is 0.0125% or more. The content of EDTA is preferably 0.02% or more, more preferably 0.03% or more. The content of EDTA is not particularly limited, but is, for example, 0.2% or less, preferably 0.1% or less, more preferably 0.05% or less. The upper limit or lower limit of the range may be, for example, 0.015, 0.02, 0.025, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, or 0.15%.

[0017] <(C) Ingredient: Citric acid> Component (C) includes citric acid hydrate, anhydrous citric acid, and citrate salts. Citric acid hydrates include citric acid monohydrate.

[0018] Examples of citrates include sodium citrate, potassium citrate, calcium citrate, and ammonium citrate. Specific examples of sodium citrate include sodium citrate, trisodium citrate, trisodium citrate monohydrate, trisodium citrate dihydrate, and the like.

[0019] Specific examples of potassium citrate include monopotassium citrate, tripotassium citrate, tripotassium citrate monohydrate, and the like. Specific examples of ammonium citrate include diammonium citrate and diammonium hydrogen citrate.

[0020] As the component (C) contained in the oral cavity composition, anhydrous citric acid and trisodium citrate are particularly preferred. The oral cavity composition may contain, as component (C), only one of the above components, or a combination of two or more of the above components.

[0021] The oral composition preferably contains a combination of two or more of the above components. The acidity of the oral composition can be adjusted depending on the combination of the above components and the ratio of each component.

[0022] The oral composition preferably contains a citrate and anhydrous citric acid. The oral composition particularly preferably contains trisodium citrate and anhydrous citric acid. In this case, the mass ratio of the citrate to anhydrous citric acid in the oral composition, for example the mass ratio (trisodium citrate / anhydrous citric acid), is not particularly limited, but is, for example, 5 or more and 100 or less. The lower limit of the mass ratio of the citrate to anhydrous citric acid is preferably 20, more preferably 30. The upper limit of the above mass ratio is preferably 50, more preferably 40. The upper limit or lower limit of the range may be, for example, 10, 20, 30, 40, 50, 60, 70, 80, or 90.

[0023] The oral composition contains component (C), which is a citric acid-containing component, at a high concentration of 0.2% by mass or more in terms of citric acid, as shown below, compared to the content of acid components used as general pH adjusters.

[0024] In this specification, the content of component (C) in the oral composition is referred to as the "citric acid equivalent", which is the amount of component (C) contained in the oral composition converted into citric acid. The citric acid equivalent is the amount of component (C), which is a citric acid-containing component, converted into the amount of anhydrous citric acid. When the oral composition contains a combination of two or more (C) components, the citric acid equivalent is the sum of the amounts of each component converted into citric acid.

[0025] The amount of citric acid of the component (C) contained in the oral cavity composition is 0.2% or more. The amount of citric acid is preferably 0.3% or more, more preferably 0.4% or more. The amount of citric acid is not particularly limited, but is, for example, 10% or less, preferably 5% or less, more preferably 2% or less. The upper limit or lower limit of the range may be, for example, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 3, 4, 5, 6, 7, 8, or 9%.

[0026] <Other ingredients> The oral composition may contain other components in addition to the above-mentioned components depending on the application purpose, form, use, etc. Examples of the other components include surfactants, flavoring agents, sweeteners, humectants, binders, preservatives, colorants, chelating agents, medicinal ingredients, bases, abrasives, stabilizers, etc. The other components may be any known components that are blended into oral compositions. The oral composition may contain only one of the above-mentioned other components alone, or may contain two or more of them in combination.

[0027] Examples of the surfactant include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants. Specific examples of nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, maltose fatty acid esters, and lactose fatty acid esters; fatty acid alkanolamides; glycerin fatty acid esters; sorbitan fatty acid esters; fatty acid monoglycerides; polyoxyethylene alkyl ethers having a polyoxyethylene addition coefficient of 8 to 10 and an alkyl group having 13 to 15 carbon atoms; polyoxyethylene alkyl phenyl ethers having a polyoxyethylene addition coefficient of 10 to 18 and an alkyl group having 9 carbon atoms; diethyl sebacate; polyoxyethylene hydrogenated castor oil; and polyoxyethylene sorbitan fatty acid.

[0028] Specific examples of anionic surfactants include sulfate salts such as sodium polyoxyethylene lauryl ether sulfate; sulfosuccinates such as sodium lauryl sulfosuccinate and sodium polyoxyethylene lauryl ether sulfosuccinate; acylamino acid salts such as sodium cocoyl sarcosine and sodium lauroyl methyl alanine; and sodium cocoyl methyl taurate.

[0029] Specific examples of the cationic surfactant include distearyl dimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, N-coconut oil fatty acid acyl-L-arginine ethyl-DL-pyrrolidone carboxylate, and the like.

[0030] Specific examples of amphoteric surfactants include acetate betaine type surfactants such as lauryl dimethylamino acetate betaine and coconut oil fatty acid amidopropyl dimethylamino acetate betaine; imidazoline type surfactants such as N-cocoyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium; and amino acid type surfactants such as N-lauryl diaminoethyl glycine.

[0031] Specific examples of flavoring agents include menthol, carboxylic acid, anethole, eugenol, methyl salicylate, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronenyl acetate, methyl eugenol, cineole, thymol, 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, fennel oil, cinnamon oil, anise oil, cinnamaldehyde, peppermint oil, and vanillin.

[0032] Specific examples of sweeteners include saccharin sodium, acesulfame potassium, stevioside, neohesperidyl dihydrochalcone, perillartine, thaumatin, aspartyl phenylalanyl methyl ester, and p-methoxycinnamic aldehyde.

[0033] Specific examples of the wetting agent include sorbitol, ethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, polypropylene glycol, xylitol, maltitol, lactite, polyoxyethylene glycol, and the like.

[0034] Specific examples of binders include cellulose derivatives such as sodium carboxymethylcellulose, carboxymethylethylcellulose salts, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, crystalline cellulose, and crystalline cellulose-carmellose sodium; microbially produced polymers such as xanthan gum; natural polymers or natural rubbers such as tragacanth gum, karaya gum, gum arabic, guar gum, carrageenan, dextrin, agar, pectin, pullulan, gellan gum, locust bean gum, and sodium alginate; synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, polyvinyl methyl ether, and sodium polyacrylate; thickening silica, inorganic binders such as Veegum; and cationic binders such as O-[2-hydroxy-3-(trimethylammonio)propyl]hydroxyethylcellulose chloride.

[0035] Specific examples of preservatives include parabens such as methylparaben, ethylparaben, propylparaben, and butylparaben, sodium benzoate, phenoxyethanol, and alkyldiaminoethylglycine hydrochloride.

[0036] Specific examples of colorants include legal dyes such as Blue No. 1, Yellow No. 4, Red No. 202, and Green No. 3; mineral dyes such as ultramarine, enhanced ultramarine, and Prussian blue; and titanium oxide. Specific examples of the chelating agent include, in addition to EDTA, phytic acid, pyrophosphoric acid, polyphosphoric acid, malic acid, and the like.

[0037] Specific examples of medicinal ingredients other than cetylpyridinium chloride hydrate include vitamin E such as d1-α-tocopherol acetate, tocopherol succinate, or tocopherol nicotinate, vitamin C such as ascorbic acid, sodium ascorbate, or magnesium ascorbyl phosphate, vitamin B6 such as pyridoxine hydrochloride, amphoteric bactericides such as glycyrrhizinate, glycyrrhetinic acid, and dodecyldiaminoethylglycine, nonionic bactericides such as triclosan, isopropylmethylphenol, polyoxyethylene lauryl ether, and hinokitiol, anionic bactericides such as sorbic acid, chlorhexidine hydrochloride, benzyl chloride, and the like. Examples of effective antiseptics include cationic antiseptics such as benzoylcholine, benzalkonium chloride, and benzethonium chloride; enzymes such as dextranase, amylase, protease, mutanase, lysozyme, and lytic enzyme (Retech Enzyme); alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate; fluorides such as sodium fluoride and stannous fluoride; tranexamic acid, epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholesterol, copper chlorophyllin sodium, chlorophyll, sodium chloride, callopeptide, allantoin, carbazochrome, potassium nitrate, and palatinit.

[0038] Specific examples of the base include alcohols, silicone, apatite, white petrolatum, paraffin, liquid paraffin, microcrystalline wax, squalane, plastibase, and the like.

[0039] Specific examples of the alcohols include ethyl alcohol, lauryl alcohol, and myristyl alcohol. Specific examples of abrasives include calcium carbonate, magnesium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, magnesium phosphate, silica, zeolite, sodium metaphosphate, aluminum hydroxide, magnesium hydroxide, calcium pyrophosphate, red iron oxide, calcium sulfate, and silicic anhydride.

[0040] Specific examples of the stabilizer include sodium thiosulfate, sodium sulfite, calcium lactate, lanolin, triacetin, castor oil, magnesium sulfate, and the like. <Application form, use, and dosage form> The application form of the oral composition and the protease activity inhibitor is not particularly limited, and can be used as, for example, medicine, quasi-drug, or cosmetic. The oral composition and the protease activity inhibitor can be used for any known purpose. For example, the oral composition and the protease activity inhibitor can be used for any known purpose. Examples of the applications include chewing agents, oral dissolving agents, oral disintegrating agents, tongue care agents, oral fresheners, toothpastes, mouthwashes, gargles, liquid dentifrices, biofilm dispersants, oral odor prevention agents, gum massage agents, oral moisturizing agents, tongue coating removers, oral application agents, oral germicides, throat germicides, oral throat agents, periodontal disease prevention agents, periodontal disease treatment agents, denture mounting agents, denture coating agents, denture stabilizers, denture preservatives, denture cleaners, and implant care agents.

[0041] The dosage form of the oral composition and the protease activity inhibitor is not particularly limited, and for example, by containing a solvent such as water or alcohol, the composition can be applied in the form (dosage form) of an ointment, paste, spray, gel, liquid, suspension, gum, tablet, drop, etc.

[0042] The type of water used as a solvent is not particularly limited, and for example, distilled water, pure water, ultrapure water, purified water, tap water, etc. can be used. The type of alcohol used as a solvent is not particularly limited, and for example, ethanol can be used. A mixture of water and alcohol can also be used.

[0043] The oral composition and the protease activity inhibitor are preferably used for preventing periodontal disease. The oral composition and the protease activity inhibitor are particularly preferably in the form of a liquid formulation. When the oral composition and the protease activity inhibitor are in liquid form, the content of the solvent such as water is not particularly limited, but is preferably from 60% by mass to 99.8% by mass, and more preferably from 65% by mass to 90% by mass.

[0044] <Action and Effects> The operation of this embodiment will be described. The oral composition and protease activity inhibitor exhibit a protease activity inhibitory effect by containing the above-mentioned components (A), (B), and (C), by containing component (B) at a specified concentration or more, and by containing component (C) at a high concentration. For example, they exhibit an inhibitory effect on the protease activity of gingipain. Hereinafter, the protease activity of gingipain may also be referred to as gingipain activity. The greater the amount of citric acid equivalent, the stronger the inhibitory effect on gingipain activity.

[0045] By inhibiting gingipain activity, periodontal disease can be prevented. By inhibiting gingipain activity, the progression of periodontal disease can be suppressed. The effects of this embodiment will be described.

[0046] (1) The oral composition and protease activity inhibitor of the present embodiment contain component (A), component (B), and component (C). By containing component (B) at a specified concentration or more and containing component (C), which is a citric acid-containing component, at a high concentration, the gingipain activity inhibitory effect is suitably exhibited.

[0047] (2) By inhibiting gingipain activity, it is expected that the effects of preventing periodontal disease, suppressing the progression of periodontal disease, and suppressing the destruction of periodontal tissues can be achieved. The above embodiment can be modified as follows: This embodiment and the following modifications can be combined with each other to the extent that no technical contradiction occurs.

[0048] May also be applied to pets, livestock and other captive animals other than humans. EXAMPLES

[0049] The oral composition of the present embodiment will be described in more detail with reference to the following examples. Note that the oral composition is not limited to the configurations described in the examples. <Preparation of sample solution> Sample solutions were prepared for Examples 1 to 6 and Comparative Examples 1 to 8. The contents of components contained in each sample solution for Examples 1 to 6 and Comparative Examples 1 to 8 are as shown in Tables 1 and 2. EDTA·2Na was used as EDTA as component (B) in the tables. The remainder of each sample solution was water.

[0050] [Table 1]

[0051] [Table 2] <Preparation of bacterial solution> 10 6 Porphyromonas gingivalis W83 strain (hereinafter sometimes referred to as "Pg") at 10 cells / mL was thawed and seeded into a test tube containing 10 mL of modified GAM medium. The test tube was then cultured at 37°C under anaerobic conditions for one day to prepare a preculture. 1 mL of the bacterial liquid obtained in the preculture was transferred to a new test tube containing 10 mL of modified GAM medium and cultured at 37°C under anaerobic conditions for one day to prepare a main culture. The Pg obtained in the main culture was adjusted to a concentration of O.D600 = 1.0 in modified GAM medium to prepare a culture solution.

[0052] <Protease activity inhibition test> Using a 96-well plate, 100 μL of the sample solution was mixed with 100 μL of culture solution. A collagen disk (AteloCell Honeycomb Disk 96, manufactured by Koken Co., Ltd.) was placed in each well and the collagen disk was immersed in the mixed solution. A collagen disk was placed in a well to which only 200 μL of water had been added as a control. The mixture was incubated at 37°C under anaerobic conditions. After 4 days, the collagen disk was observed using a microscope.

[0053] <Evaluation> The inhibitory effect on gingipain activity was evaluated based on the results of observation after 4 days. Figure 1 shows a photograph taken after observation after 4 days.

[0054] As shown in Figure 1, in the control, the pores were clear and the collagen disc structure was not destroyed. The less the collagen disc structure was destroyed, the more the gingipain activity was inhibited. The evaluation criteria are shown below. The results are shown in Table 1.

[0055] Evaluation criteria ○ (Excellent): Compared with the control, the structure of the collagen disc was not destroyed. × (bad): The structure of the collagen disc is disintegrated as compared with the control.

[0056] 1 and Table 1, collagen was finely decomposed and the structure of the collagen disk was destroyed in Comparative Examples 1 to 3. In Comparative Examples 1 to 3, no inhibitory effect on gingipain activity was confirmed.

[0057] In contrast, the collagen disc structure was not destroyed in Examples 1 to 4. It was confirmed that Examples 1 to 4 exhibited excellent gingipain activity inhibitory effect. In Examples 1 to 4, the content of EDTA as component (B) is 0.0125% or more, and the content of component (C) is 0.2% or more in terms of citric acid. In contrast, in Comparative Examples 1 to 3, the content of EDTA as component (B) is 0.0125% or more, but the content of component (C) is less than 0.2% in terms of citric acid. From the results of Examples 1 to 4 and Comparative Examples 1 to 3, it can be seen that the gingipain activity inhibitory effect is exerted when the content of component (C) is 0.2 mass% or more in terms of citric acid.

[0058] 1 and Table 2, collagen was finely decomposed and the structure of the collagen disk was destroyed in Comparative Examples 4 to 8. In Comparative Examples 4 to 8, no inhibitory effect on gingipain activity was confirmed.

[0059] In contrast, the collagen disc structure was not destroyed in Examples 5 and 6. It was confirmed that Examples 5 and 6 exhibited excellent gingipain activity inhibitory effect. In Examples 1, 2, 5, and 6, the content of EDTA as component (B) is 0.0125% or more, and the content of component (C) is 0.2% or more calculated as citric acid. In contrast, in Comparative Examples 4 to 8, the content of component (C) is 0.2% or more calculated as citric acid, but the content of EDTA as component (B) is less than 0.0125%. From the results of Examples 1, 2, 5, and 6 and Comparative Examples 4 to 8, it can be seen that the gingipain activity inhibitory effect is exerted when the content of component (B) is 0.0125% by mass or more.

[0060] In other words, it is found that the gingipain activity inhibitory effect is exerted when the composition contains components (A), (B), and (C), the content of component (B) is 0.0125 mass% or more, and the content of component (C) is 0.2 mass% or more, calculated as citric acid.

Claims

1. (A) cetylpyridinium chloride hydrate, (B) at least one selected from the group consisting of ethylenediaminetetraacetic acid and salts thereof; (C) at least one selected from the group consisting of citric acid hydrate, anhydrous citric acid, and a citrate salt; The content of the (B) component is 0.0125% by mass or more, The content of the component (C) is 0.2% by mass or more in terms of citric acid. Oral composition.

2. The content of the component (A) is 0.05% by mass or more. The oral composition according to claim 1 .

3. For preventing periodontal disease The oral composition according to claim 1 or 2.

4. (A) cetylpyridinium chloride hydrate, (B) at least one selected from the group consisting of ethylenediaminetetraacetic acid and salts thereof; (C) at least one selected from the group consisting of citric acid hydrate, anhydrous citric acid, and a citrate salt; The content of the (B) component is 0.0125% by mass or more, The content of the component (C) is 0.2% by mass or more in terms of citric acid. Protease activity inhibitor.

5. Inhibits the protease activity of gingipain The protease activity inhibitor according to claim 4 .

Images