JP7064938B2 - Oral composition - Google Patents

Description

The present invention relates to an oral composition.

With the aging of society, the number of root caries that develops in exposed dentin due to gingival recession is increasing, and its prevention is desired.
As for the pathogenic mechanism of root surface caries (dentin caries) that develops in dentin, first, bacteria in plaque adhering to the surface of dentin cause sugar metabolism and acid is produced. The acid produced elutes (decalcifies) the mineral components of dentin, exposing the organic (collagen) layer. Then, the exposed collagen layer is physically and chemically destroyed, and a substantial defect occurs at the root of the tooth, resulting in root caries.

Conventionally, as a method for preventing dentin caries, a method of suppressing demineralization with fluoride or promoting remineralization is known. However, since the mineral density of dentin is as low as about 50% as compared with the enamel having a mineral density of about 97%, it is physically and chemically vulnerable. Therefore, the preventive effect of the conventional method has never been high. In view of such problems, Patent Documents 1 to 10 propose techniques for suppressing demineralization and promoting remineralization.

Patent Document 1 discloses an oral composition containing pyrrolidone carboxylic acid and polyphenol for the purpose of improving the effect of suppressing dentin caries including suppression of collagen decomposition.
Patent Document 2 describes dentin and / or lactoferrin, a fluorine compound, and nitric acid, phosphoric acid, hydrochloric acid, and for the purpose of blocking dentin tubules, improving dentin acid resistance and hardness, and stabilizing fluorine. An oral composition comprising a K salt or a Na salt of an acid selected from sulfuric acid is disclosed.
Patent Document 3 discloses an oral composition containing a ryugan seed extract, a fluorine compound and a sugar alcohol for the purpose of blocking dentin tubules, suppressing dentin decalcification, stabilizing fluorine and stabilizing the preparation. There is.

Patent Document 4 discloses a root surface caries preventive agent composed of flavanones and / or glycosides thereof for the purpose of suppressing collagen decomposition and suppressing dentin demineralization.
Patent Document 5 contains hydrolyzed silk and light calcium carbonate having an average particle size of primary particles in the range of 0.04 to 0.5 μm for the purpose of suppressing mineral elution of dentin. The oral composition having is disclosed.
Patent Document 6 has, for the purpose of promoting remineralization, a monomer having a hydroxyl group and a monomer having a phosphorus atom-containing acidic group having a compounding amount of 5 to 200% by weight with respect to the monomer having a hydroxyl group as components. Tooth remineralization promoters are disclosed.

Patent Document 7 contains at least one selected from the group consisting of (A) zinc compound, (B) aldehyde compound, phenol compound and tea-extracted polyphenol compound for the purpose of preventing root caries. The oral composition having as is disclosed.
Patent Document 8 discloses an oral composition containing a water-soluble aluminum compound, fluoride and a water-soluble calcium compound for the purpose of suppressing dentin hypersensitivity and suppressing tooth root surface and dentin caries. There is.
Patent Document 9 discloses an oral composition containing a water-soluble aluminum compound and fluoride for the purpose of suppressing dentin hypersensitivity and providing a good feeling of use.
Patent Document 10 describes pyrrolidone carboxylic acid, 6-oxo-2-piperidin carboxylic acid, 3- (2-oxo-1-azepanyl) propanoic acid, and 3- (2-oxo-1-azepanyl) propanoic acid for the purpose of suppressing dentin caries and providing a good feeling of use. An oral composition containing one or more lactam compounds selected from the group consisting of these salts, a water-soluble divalent metal salt, and a water-soluble fluorine compound is disclosed.

International Publication No. 2013/47826 Japanese Unexamined Patent Publication No. 2012-232937 Japanese Unexamined Patent Publication No. 2011-168510 Japanese Unexamined Patent Publication No. 2009-256341 Japanese Unexamined Patent Publication No. 2007-176862 Japanese Unexamined Patent Publication No. 2006-8596 Japanese Unexamined Patent Publication No. 11-228368 Japanese Unexamined Patent Publication No. 5-155746 Japanese Unexamined Patent Publication No. 5-155745 Japanese Unexamined Patent Publication No. 2016-145156

However, further improvement is required for the effect of suppressing dentin caries.

An object of the present invention is to provide an oral composition having significantly improved acid resistance of dentin and suppression of collagen decomposition.

As a result of diligent studies on the above-mentioned problems, the present inventors have determined that at least one of pyrrolidone carboxylic acid and an alkali metal salt thereof, at least one of a basic amino acid and a salt thereof, a water-soluble fluorine compound, zinc pyrrolidone carboxylate, and the like. It has been found that the above-mentioned problems can be solved by using an oral composition containing the above-mentioned substances, and the present invention has been completed.
That is, the present inventors provide the following [1] to [7].
[1] Component (A): At least one of pyrrolidone carboxylic acid and an alkali metal salt thereof (hereinafter, also referred to as "component (A)"), and component (B): at least one of a basic amino acid and a salt thereof ( Hereinafter, "(B) component"), (C) component: a water-soluble fluorine compound (hereinafter, also referred to as "(C) component"), and (D) component: zinc pyrrolidone carboxylate (hereinafter, "(). D) Ingredients ”) and an oral composition containing.
[2] The oral composition according to the above [1], wherein the content of the component (A) is 0.1 to 10% by mass.
[3] The oral composition according to the above [1] or [2], wherein the content of the component (B) is 0.05 to 20% by mass.
[4] The oral composition according to any one of the above [1] to [3], wherein the content of the component (C) is 0.01 to 0.5% by mass in terms of fluorine atoms.
[5] The oral composition according to any one of the above [1] to [4], wherein the content of the component (D) is 0.1 to 10% by mass.
[6] The oral composition according to any one of the above [1] to [5], wherein the component (B) is at least one selected from the group consisting of arginine, lysine, and salts thereof.
[7] The oral composition according to any one of the above [1] to [6], wherein the component (C) is sodium fluoride or sodium monofluorophosphate.

According to the present invention, it is possible to provide an oral composition having significantly improved acid resistance of dentin and suppression of collagen decomposition.

Hereinafter, the present invention will be described in detail according to the preferred embodiment thereof.

The oral composition of the present invention contains (A) component, (B) component, (C) component, and (D) component. By containing the components (A) to (C), the acid resistance of dentin can be significantly improved. Further, by containing the component (D), the collagen decomposition inhibitory effect can be remarkably improved.

[1. (A) component]
The component (A) is at least one of pyrrolidone carboxylic acid and an alkali metal salt thereof. The structural formula of pyrrolidone carboxylic acid is shown in the following formula (1).

Pyrrolidone carboxylic acid is usually produced by dehydrating glutamic acid extracted from seaweed / wheat flour and sugar cane, and has a structure represented by the above formula (1). PCA soda is a substance in which sodium ions are bound. PCA soda has better stability such as oxidative stability than PCA. It is also a component of NMF (Natural Moisturizing Factor), which is a water-retaining substance in the stratum corneum of the skin.

Examples of the alkali metal salt of pyrrolidone carboxylic acid include sodium salts and potassium salts. As the pyrrolidone carboxylic acid or an alkali metal salt thereof, those synthesized according to a known scheme may be used, or commercially available products may be used. As a commercial product of pyrrolidone carboxylic acid, "AJIDEW A-100 (registered trademark)" manufactured by Ajinomoto Healthy Supply Co., Ltd., and as a commercial product of sodium salt of pyrrolidone carboxylic acid, "AJIDEW-N-50, PCA soda (AI =)" 50% aqueous solution) ”and the like.

The content of the component (A) in the oral composition of the present invention is not particularly limited, but the lower limit thereof is 0.1% by mass with respect to the entire oral composition from the viewpoint of further improving the acid resistance effect of dentin. % Or more is preferable, and 0.5% by mass or more is more preferable. The upper limit thereof is not particularly limited, but is preferably 10% by mass or less, more preferably 5% by mass or less, based on the entire oral composition, from the viewpoint of deterioration of the extrudability due to an increase in the viscosity of the preparation.
The content of the component (A) is preferably 0.1 to 10% by mass, more preferably 0.5 to 10% by mass, and even more preferably 0.5 to 5% by mass with respect to the entire oral composition.

[2. (B) component]
The component (B) is a basic amino acid. Examples of basic amino acids include arginine, lysine, ornithine and histidine. Of these, arginine and lysine are preferred. The basic amino acid may be an L-form, a D-form, or a mixture of both optical isomers in an arbitrary ratio.
The component (B) may be a salt of a basic amino acid. Examples of the salt of arginine include L-arginine L-glutamate, L-arginine L-aspartate, and L-arginine hydrochloride. Of these, L-arginine L-glutamate is preferable. Examples of the lysine salt include L-lysine L-glutamate, L-lysine L-aspartate, and L-lysine hydrochloride. Of these, L-lysine hydrochloride is preferable.
The component (B) is preferably at least one selected from the group consisting of arginine, lysine, and salts thereof.

The component (B) may be derived from a natural product such as an animal or a plant, may be chemically synthesized, or may be a commercially available product. Examples of commercially available arginine products include "L-arginine C grade" manufactured by Ajinomoto Co., Inc. Examples of commercially available lysine hydrochloride include “L-lysine hydrochloride (food additive)” manufactured by Ajinomoto Co., Inc.

The content of the component (B) in the oral composition of the present invention is not particularly limited, but the lower limit thereof is set with respect to the entire oral composition from the viewpoint of promoting the acid resistance improving effect of the dentin of the component (A). It is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.2% by mass or more. The upper limit thereof is not particularly limited, but is preferably 20% by mass or less with respect to the entire oral composition from the viewpoint of worsening irritation to the oral cavity.
The content of the component (B) is preferably 0.05 to 20% by mass, more preferably 0.1 to 20% by mass, and even more preferably 0.2 to 20% by mass with respect to the entire oral composition.
The content of the component (B) when two or more kinds of the component (B) are used is the total content.

[3. (C) component]
The component (C) is a water-soluble fluorine compound. Examples of the water-soluble fluorine compound include sodium fluoride, potassium fluoride, ammonium fluoride, tin fluoride, amine fluoride, sodium monofluorophosphate, potassium monofluorophosphate, sodium silicon fluoride, and calcium silicon fluoride. Can be mentioned. Of these, sodium fluoride and sodium monofluorophosphate are preferable.

The content of the component (C) in the oral composition of the present invention is not particularly limited, but the lower limit thereof is 0.01% by mass (100 ppm) or more in terms of fluorine atoms from the viewpoint of obtaining a sufficient acid resistance effect. It is preferably 0.05% by mass (500 ppm) or more, more preferably. Further, the upper limit thereof is not particularly limited, but from the viewpoint that improvement in fluorine uptake cannot be obtained, 0.5% by mass (5000 ppm) or less is preferable with respect to the entire oral composition, and 0.4% by mass is preferable. (4000 ppm) or less is more preferable.
The content of the component (C) is preferably 0.01 to 0.5% by mass (100 to 5000 ppm), more preferably 0.05 to 0.4% by mass (500 to 4000 ppm) with respect to the entire oral composition. preferable.

[4. (D) component]
The component (D) is zinc pyrrolidone carboxylate. As described above, pyrrolidonecarboxylic acid is usually produced by dehydrating glutamic acid extracted from seaweed / wheat flour and sugar cane, and zinc ion is bound to this to form zinc pyrrolidonecarboxylate (hereinafter, "PCA zinc"). Also called).

As the pyrrolidone carboxylic zinc, those synthesized according to a known scheme may be used, or commercially available products may be used. Examples of commercially available products of zinc pyrrolidone carboxylate include AJIDEW ZN-100 (manufactured by Ajinomoto Co., Inc.).

The content of the component (D) in the oral composition of the present invention is not particularly limited, but the lower limit thereof is 0.1 with respect to the entire oral composition from the viewpoint of further improving the collagen decomposition inhibitory effect of dentin. By mass or more is preferable, and 0.5% by mass or more is more preferable. The upper limit thereof is not particularly limited, but is preferably 10% by mass or less from the viewpoint of worsening irritation to the oral cavity. Further, from the viewpoint of deterioration of the extrudability due to an increase in the viscosity of the preparation, 5% by mass or less is more preferable.
The content of the component (D) is preferably 0.1 to 10% by mass, more preferably 0.5 to 10% by mass, still more preferably 0.5 to 5% by mass, based on the entire oral composition.

[5. ratio]
The following can be said as the composition ratio of the components (A) to (D) in the oral composition of the present invention.
The ratio of the component (B) to the component (A) ((B) / (A)) is preferably 0.033 to 20, more preferably 0.067 to 6.7.
The ratio of the component (C) to the component (A) ((C) / (A)) is preferably 0.003 to 1, more preferably 0.010 to 0.20.
The ratio of the component (D) to the total of the components (A) to (C) ((D) / {(A) + (B) + (C)}) may be 0.020 to 1.96. It is preferably 0.098 to 1.96, more preferably 0.098 to 1.96.

[6. Optional ingredient]
In addition to the above-mentioned components, the oral composition of the present invention contains any components necessary for the composition as long as the effects of the present invention such as suppression of collagen decomposition and improvement of acid resistance are not impaired. Can be done. Optional ingredients include, for example, abrasives, binders, surfactants, thickeners, sweeteners, preservatives, fragrances, acidulants, lubricants, colorants, brighteners, fluidizers, binders, etc. Examples include disintegrants, medicinal ingredients, pH regulators, solvents such as water, and excipients. Specific examples of optional components are shown below, but the components that can be blended in the composition of the present invention are not limited thereto.

Examples of the polishing agent include silicon dioxide (hereinafter, silicon dioxide as a polishing agent is also referred to as "polishable silica" or "silicic acid anhydride (polishable)"), crystalline silica, amorphous silica, and silica gel. , Silica gel abrasives such as aluminosilicate, zeolite, calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, tertiary magnesium phosphate, Examples thereof include silica gel silicate, calcium ferric phosphate, hydroxyapatite, calcium tetraphosphate, and synthetic resin-based abrasives.

The liquid absorption amount of the abrasive silica is usually 0.5 to 2.0 mL / g, preferably 0.7 to 1.5 mL / g.
The amount of liquid absorbed is a value measured by the following method. That is, 1 g of the sample is weighed on a glass plate, and a 42.5 mass% glycerin aqueous solution is dropped using a burette and mixed with a spatula so that the liquid becomes uniform. The end point is when the sample becomes one mass and can be peeled off cleanly from the glass plate with a spatula, and the amount of glycerin aqueous solution required for 1.0 g of the sample is expressed as the amount of liquid absorbed (mL / g).

The abrasive can be used alone or in combination of two or more. When the abrasive is contained, the content of the dentifrice is preferably 2 to 40% by mass, more preferably 5 to 20% by mass, based on the whole composition. In the mouthwash, it is preferably 10% by mass or less, more preferably 5% by mass or less of the whole composition.

Examples of the binder include an organic binder and an inorganic binder. The binder can be used alone or in combination of two or more.

Examples of the organic binder include sodium polyacrylate, carrageenan, carboxymethyl cellulose, sodium alginate, xanthan gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, propylene glycol alginate, purulan, gelatin, and arabic gum. Guar gum, locust bean gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer can be mentioned.
Examples of the inorganic caking agent include anhydrous silicic acid (hereinafter, anhydrous silicic acid as a clotting agent is also referred to as "thickening silica" or "anhydrous silicic acid (thickening)") and bentonite. Of these, anhydrous silicic acid (thickening) is preferable.

The liquid absorption amount of the viscous silica is preferably 2.1 mL / g or more, and more preferably 2.1 to 5 mL / g.

The organic binder and the inorganic binder may be one kind or a combination of two or more kinds, respectively. The binder may be a combination of an organic binder and an inorganic binder.

When an organic binder is used, its content is usually 0.01 to 3.5% by mass based on the entire oral composition. When an inorganic binder is used, its content is preferably 1 to 10% by mass, more preferably 1 to 7% by mass, still more preferably 2 to 6% by mass.

As the surfactant, for example, an anionic surfactant, a nonionic surfactant, an amphoteric surfactant and the like can be used.

Examples of the anionic surfactant include N-acylamino acid salt, α-olefin sulfonate, N-acylsulfonate, alkyl sulfate, and sulfate of glycerin fatty acid ester. Of these, N-acylamino acid salts, α-olefin sulfonates, alkyl sulfates and the like are preferable in terms of versatility, and lauroyl sarcosine sodium and alkyl chain carbon chain lengths are preferable in terms of foamability and hardness water resistance. Of the above, sodium α-olefin sulfonate, sodium lauryl sulfate and the like having 10 to 16 carbon atoms are more preferable.
Examples of the N-acylamino acid salt include N-acyltaurine salt, which has a linear or branched saturated or unsaturated hydrocarbon group having 8 to 18 carbon atoms, preferably 12 to 16 carbon atoms. , Methyl taurine salts such as lauroyl methyl taurine salt, coconut oil fatty acid methyl taurine salt, myristyl methyl taurine salt; methyl alanine salts such as lauroyl methyl alanine salt; glutamates such as lauroyl glutamic acid and myristoyl glutamic acid can also be used.

Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene hydrogenated castor oil, glycerin ester polyoxyethylene ether, sucrose fatty acid ester, and alkylolamide. , Glycerin fatty acid ester. Of these, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, alquilolamide, sorbitan fatty acid ester and the like are preferably used in terms of versatility. In the polyoxyethylene alkyl ether, the carbon chain length of the alkyl chain is preferably 14 to 18 in terms of the number of carbon atoms. The polyoxyethylene alkyl ether preferably has an average number of moles of ethylene oxide added of 15 to 30. The polyoxyethylene hydrogenated castor oil preferably has an average number of moles of ethylene oxide added (average addition EO) of 20 to 100. In the alkylol amide, the carbon chain length of the alkyl chain is preferably 12 to 14 carbon atoms. The sorbitan fatty acid ester preferably has 12 to 18 carbon atoms in the fatty acid. The polyoxyethylene sorbitan fatty acid ester preferably has 16 to 18 carbon atoms in the fatty acid. Further, the polyoxyethylene sorbitan fatty acid ester preferably has an average number of moles of ethylene oxide added of 10 to 40.

Examples of the amphoteric surfactant include an alkyl betaine-based surfactant, an amine oxide-based surfactant, and an imidazolinium betaine-based surfactant. Specific examples of the amphoteric tenside include coconut oil fatty acid amide alkyl betaine, and coconut oil fatty acid amide propyl betaine is preferable.

The surfactant can be used alone or in combination of two or more. When the oral composition contains a surfactant, the content thereof is usually 10% by mass or less, preferably 0.01 to 5% by mass, based on the entire oral composition.

Examples of the viscous agent include propylene glycol, butylene glycol, glycerin, sorbitol (sorbitol), polyethylene glycol and the like. Its content is usually 5 to 70% by mass with respect to the entire oral composition.

Examples of the sweetener include sodium saccharin, stebioside, neohesperidin hydrochalcone, glycyrrhizin, perillartine, p-methoxycinnamic aldehyde, thaumatin, palatinose, maltitol, xylitol, arabitol and the like.
The sweetener can be used alone or in combination of two or more. When a sweetener is used, the content can be appropriately determined as long as the effect of the present invention is not impaired.

Examples of the preservative include paraoxybenzoic acid esters such as sodium benzoate, methylparaben, ethylparaben, and butylparaben, ethylenediamine tetraacetate, and benzalconium chloride.
Preservatives can be used alone or in combination of two or more. When a preservative is used, the content can be appropriately determined as long as the effect of the present invention is not impaired.

Examples of the fragrance include natural fragrances, synthetic fragrances (single fragrances), and blended fragrances (oil-fat fragrances (oil-based fragrances), powder fragrances, etc.). The fragrance may be used alone or in combination of two or more of the above fragrances.

Natural fragrances include, for example, mastic oil, parsley oil, anis oil, eucalyptus oil, winter green oil, cassia oil, menthol oil, spear mint oil, peppermint oil, lemon oil, coriander oil, orange oil, mandarin oil, lime oil. , Lavender oil, laurel oil, chamomile oil, cardamon oil, caraway oil, bay oil, lemongrass oil, pine needle oil, neroli oil, rose oil, jasmine oil, iris concrete, peppermint absolute, rose absolute, orange flower, citrus Oil, mixed fruit oil, strawberry oil, cinnamon oil, clove oil, grape oil, thyme oil, sage oil, peppermint oil, rosemary oil, perilla oil, majorum oil, origanum oil, grapefruit oil, sweetie oil, yuzu oil, mango Examples thereof include absolute, orange flower absolute, capsicum extract, ginger ole oledin, pepper ole oledin, capsicum ole oledin and the like.

As a single fragrance, for example, 1-menthol, carboxylic, eugenol, anator, methyl salicylate, timole, cinnamaldehyde, linalol, linalyl acetate, limonene, ossimen, n-decyl alcohol, citronellol, varnish, menthon, mentyl acetate, pinen, Octylaldehyde, citral, pregon, calbeer acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allylcyclohexanepropionate, methyl anthranilate, ethyl methyl anthranilate, vanillin, undecalactone (γ-undecalactone, δ-Undecalactone, etc.), Hexanal (trans-2-hexenal, etc.), ethinone alcohol, propyl alcohol, butanol, isoamyl alcohol, hexenol (cis-3-hexenol, etc.), dimethylsulfade, cycloten, furfural, trimethylpyrazine , Ethyllactate, ethylrioacetate, cineole (1,8-cineole, etc.), mensoflan, linalol oxide, vanillylbutyl ether, isopregol, flaneol, ethylcyclopentenolone, 2-methylbutyric acid, propionic acid, decalactone ( γ-decalactone, δ-decalactone, etc.), nonalactone (γ-nonalactone, δ-nonalactone, etc.), hexalactone (γ-hexalactone, δ-hexalactone, etc.), isoamyl acetate, benzaldehyde, hexyl acetate, ethyl-2-methyl Butyrate, benzyl alcohol, α-terpineol, phenylethyl glycidate, phenylethyl alcohol, allyl hexanoate, methyl cinnamate, ethyl β-methylthiopropionate, cis-6-nonenor, caron, methyl jasmonate. Be done.

The single fragrance may be a cooling sensation agent. Examples of cooling agents include menthol, N-ethyl-p-menthan-3-carboxyamide, N- (ethoxycarbonylmethyl) -3-p-menthancarboxyamide, N, 2,3-trimethyl-2-isopropylbutaneamide. , 3- (L-methoxy) Propane-1,2-diol, Menthyl Lactate (Mentyl Lactate), Monomentyl Succinate, Menthone Lyserine Acetal, 3-l-Mentoxy Propane-1,2-diol, Menthone Lyserine Ether, Spirantol , Monomenthol succinate and the like are exemplified.

The blended fragrance is a fragrance made by blending a single fragrance and / or a natural fragrance. For example, Mentor Micron, Strawberry Flavor, Apple Flavor, Banana Flavor, Pineapple Flavor, Grape Flavor, Mango Flavor, Tropical Fruit Flavor, Butter Flavor, Milk Flavor, Yogurt Flavor, Fruit Mix Flavor, Herb Mint Flavor.

Examples of fragrances include essential oils such as peppermint, sparemint, rosemary oil, sage oil, perilla oil, lemon oil and orange oil, fruit-based essences such as lemon and strawberry, 1-menthol, carboxylic, eugenol, anetol and linalool. , Limonene, ossimen, cineole, n-decyl alcohol, citronellol, wanillin, α-terpineol, methyl salicylate, timole and other fragrance materials are preferred.

The form of the fragrance is not limited, and it may be an essential oil, an extract, a solid substance, or a powder obtained by spray-drying any of these. When the oral composition contains a fragrance material, the content thereof is preferably 0.000001 to 1.5% by mass with respect to the entire oral composition. When a perfume for perfume using the above perfume material is contained, the content thereof is preferably 0.1 to 2.0% by mass with respect to the entire oral composition.

Examples of the acidulant include organic acids such as citric acid, malic acid, succinic acid and tartaric acid. When the acidulant is contained, the content is preferably 0.001 to 5% by mass with respect to the entire composition.

Examples of the lubricant include glycerin fatty acid esters and the like.

Coloring agents include, for example, natural pigments such as Benibana red pigment, gardenia yellow element, gardenia blue pigment, perilla pigment, red koji pigment, red cabbage pigment, carrot pigment, hibiscus pigment, cacao pigment, spirulina blue pigment, and tamarind pigment. , Red No. 3, Red No. 104, Red No. 105, Red No. 106, Yellow No. 4, Yellow No. 5, Green No. 3, Blue No. 1 and other legal dyes, riboflavin, copper chlorophyllin sodium, titanium dioxide and the like.
When the oral composition contains a colorant, the content thereof is preferably 0.00001 to 3% by mass with respect to the entire oral composition.

Examples of the brightener include waxes such as shellac, carnauba wax, and candelilla wax, and calcium stearate.
When the oral composition contains a brightener, the content thereof is preferably 0.01 to 5% by mass with respect to the entire oral composition.

Examples of the fluidizing agent include fine particle silicon dioxide and the like.
When the oral composition contains a fluidizing agent, the content thereof is preferably 0.01 to 5% by mass with respect to the entire oral composition.

Examples of the binder include purulan, gelatin, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, Arabic gum, guar gum, locust bean gum, polyvinyl alcohol, polyvinylpyrrolidone, karaya gum and sodium carboxymethyl cellulose.
When a binder is contained, the content varies depending on the pharmaceutical product and cannot be uniformly specified. For example, in the case of a film, 0.01 to 90% by mass is usually preferable with respect to the entire composition. In the case of other than the film, 0.01 to 10% by mass is usually preferable with respect to the whole composition.

Examples of the disintegrant include pregelatinized starch, sodium alginate, crospopidone, croscarmellose, sodium carboxymethyl cellulose and the like. Disintegrants are often contained in tablets. Examples of the binder contained in the tablet confectionery include hydroxypropyl cellulose, hydroxymethyl cellulose, Karaya gum and the like. When a disintegrant and / or a binder is contained in the tablet confectionery, the content of each is preferably 0.1 to 10% by mass with respect to the entire composition.

Further, as medicinal ingredients, bactericidal or antibacterial agents such as chlorohexidine, triclosan, isopropylmethylphenol, cetylpyridinium chloride, zinc gluconate, zinc citrate; dentin preventive agents such as condensed phosphate and ethanehydroxydiphosphonate: tranexamic acid. , Anti-inflammatory agents such as glycyrrhizin dipotassium salt, ε-aminocaproic acid, Oubaku extract; Coating agents such as hydroxyethyl cellulose dimethyldiallyl ammonium chloride; Astringent agents such as allantin; antihypersensitivity agents such as strontium chloride; stain removers such as sodium polyphosphate and sodium metaphosphate; enzyme agents such as dextranase and mutanase can be mentioned.
The medicinal ingredient may be used alone or in combination of two or more. When the medicinal ingredient is used, the content can be used within a pharmaceutically acceptable range for each medicinal ingredient.

The pH of the oral composition of the present invention is preferably 7 to 8 from the viewpoint of effectiveness and stability, and the pH can be adjusted by using a pH adjuster if necessary. Examples of the pH adjuster include phosphoric acid or a salt thereof (sodium phosphate, sodium dihydrogen phosphate, etc.), citric acid or a salt thereof (sodium citrate, etc.), malic acid or a salt thereof, gluconic acid or a salt thereof, and the like. Examples thereof include maleic acid or a salt thereof, succinic acid or a salt thereof, glutamic acid or a salt thereof, lactic acid, hydrochloric acid, acetic acid, nitrate, sodium hydroxide, potassium hydroxide, sodium acetate and sodium carbonate. When a pH adjuster is contained, the content thereof can be appropriately determined as long as the effect of the present invention is not impaired.

Examples of the solvent include water and lower alcohols having 3 or less carbon atoms such as ethanol and propanol. The solvent is usually contained in liquid oral compositions. When the oral composition contains water as a solvent, the content thereof is preferably 20 to 95% by mass with respect to the entire oral composition. When the oral composition contains a lower alcohol as a solvent, the content thereof is preferably 1 to 20% by mass with respect to the entire oral composition.

Examples of the excipient include starch syrup, glucose, fructose, invert sugar, dextrin, and oligosaccharide. When the oral composition is a food preparation, it usually contains an excipient. When the excipient is contained, the content thereof can be appropriately determined as long as the effect of the present invention is not impaired.

[7. Shape, dosage form]
The shape and dosage form of the oral composition of the present invention are not particularly limited. For example, it can be prepared in various shapes such as a liquid type (liquid, liquid, paste) and a solid type (solid, solid). Examples of dosage forms include dentifrice compositions such as dentifrices, liquid dentifrices, liquid dentifrices, and powdered dentifrices, mouthwash compositions, coating composition, oral pasta, and oral refreshing agent compositions. Food forms (chewing gum, tablet confectionery, candy, toothpaste, film, troche, etc.) can be mentioned.

The oral composition of the present invention is preferably a dentifrice composition or a mouthwash composition. When the oral composition of the present invention is a dentifrice composition, it is more preferably a dentifrice.

Hereinafter, the present invention will be described in detail with reference to Examples. The following examples are for the purpose of suitably explaining the present invention, and do not limit the present invention.

[Evaluation of dentin acid resistance effect]
The dentin of the human extracted tooth was cut into sections having a thickness of 250 μm with a microcutter. A 2 mm × 2 mm window was left as a test site, and the other part was manicure-coated to prepare a human dentin sample. This sample was immersed in a 3-fold aqueous diluted solution of the composition prepared by the method for preparing a dentifrice composition shown below at room temperature for 3 minutes (hereinafter, also referred to as "composition treatment"). After washing with purified water, the mixture was immersed in 0.5 ml of a remineralized solution (1.5 mM CaCl ₂ , 5 mM KH ₂ PO ₄ , 0.1 M acetic acid, 0.1 M NaCl, pH 6.5) and incubated at 37 ° C. The composition treatment was performed twice a day, and the rest of the time was soaked in a remineralized solution, which was repeated for a total of 3 days. The sample was immersed in 0.5 ml of decalcified solution (2.2 mM CaCl ₂ , 2.2 mM KH ₂ PO ₄ , 50 mM acetic acid, pH 5.0) and incubated at 37 ° C. for 6 hours. 50 μl of this decalcified solution was collected, and the calcium concentration in the decalcified solution was measured using an atomic absorption spectrophotometer (manufactured by Hitachi, Ltd .: Z-5310). The measurement was carried out 5 times and the average value was calculated. The amount of eluted calcium was calculated from the measured calcium concentration from the following formula and evaluated according to the criteria shown below.
The control group refers to a group not treated with the compositions shown in Examples and Comparative Examples, and was similarly evaluated by the average value of 5 times.

[Scoring criteria for acid resistance effect]
A: Elution calcium amount (μg) is less than 15 μg B: Elution calcium amount (μg) is 15 μg or more and less than 20 μg C: Elution calcium amount (μg) is 20 μg or more and less than 25 μg D: Elution calcium amount (μg) is 25 μg or more

[Evaluation of collagen decomposition inhibitory effect]
The dentin of the bovine extracted tooth was cut into sections having a thickness of 300 μm with a microcutter. A window of 2 mm × 220 mm was left as a test site, and the other part was manicure-coated to prepare a bovine dentin sample. This sample was immersed in a decalcification solution (2.2 mM CaCl ₂ , 2.2 mM KH ₂ PO ₄ , 50 mM acetic acid, pH 4.0) and incubated at 37 ° C. for 48 hours. Each sample was immersed in a 3-fold aqueous diluted solution of the composition prepared by the method for preparing a dentifrice composition shown below for 3 minutes at room temperature. After washing with purified water, 37 in 50 mM PIPES buffer (0.05M PIPES, 0.15M NaCl, 0.005M CaCl ₂ , pH 6.5) in which 20 U / ml of collagenase (C9891-500MG, Sigma) derived from Clostridium histolyticum was dissolved. Soaked at ° C for 6 hours. The dentin section was placed on a slide, and an image was captured by a digital camera for microscope (DP-62 manufactured by Olympus) and image analysis was performed. The average collagen decomposition depth was calculated from the following formula and evaluated according to the criteria shown below.

[Criteria for suppressing collagen decomposition]
A: Average collagen decomposition depth (μm) is less than 50 μm B: Average collagen decomposition depth (μm) is 50 μm or more and less than 55 μm C: Average collagen decomposition depth (μm) is 55 μm or more and less than 60 μm D: Average collagen decomposition depth (Μm) is 60 μm or more

[Sensory evaluation of ease of extruding]
Ten subjects rated the ease of extruding on the following three grades based on the degree of acupressure when extruding the dentifrice composition of each composition from the tube. The average value was calculated from the scores of 10 subjects, and the ease of pushing was evaluated by the evaluation criteria shown below.
[Score]
3 points: You can easily remove the dentifrice from the tube with a slight force 2 points: You can remove the dentifrice from the tube with a slightly strong force 1 point: The dentifrice will not come out of the tube unless you hold it firmly

[Evaluation criteria]
A: Average score is 2.5 points or more and 3 points or less B: Average score is 2 points or more and less than 2.5 points C: Average score is 1.5 points or more and less than 2 points D: Average score is less than 1.5 points

[Evaluation of no irritation in the oral cavity]
Ten subjects rated the absence of oral irritation on the following four grades based on the degree of no irritation in the oral cavity immediately after brushing the teeth using the dentifrice composition. The average value of the scores of 10 subjects was calculated, and the absence of irritation in the oral cavity was evaluated by the evaluation criteria shown below.
The dentifrice was brushed by applying about 1 g of the dentifrice composition to a toothbrush, brushing for 3 minutes, and then rinsing the oral cavity with water.
[Score]
4 points: No irritation in the oral cavity 3 points: Almost no irritation in the oral cavity 2 points: Stimulation in the oral cavity was felt 1 point: Stimulation in the oral cavity was strongly felt

[Evaluation criteria]
A: Average score 3.5 points or more B: Average score 3.0 points or more and less than 3.5 points C: Average score 2.0 points or more and less than 3.0 points D: Average score less than 2.0 points

[Method for preparing dentifrice composition]
The dentifrice composition was prepared as follows. First, in purified water, (A) component: Na pyrrolidone carboxylate, (B) component: basic amino acid, (C) component: water-soluble fluorine compound, (D) component: zinc pyrrolidone carboxylate, sodium saccharin, 70% sorbit solution. , And anhydrous silicic acid (thickening) were dissolved to prepare solution X.
Separately, sodium carboxymethyl cellulose was dispersed in propylene glycol to prepare a Y solution.
After adding the Y solution and titanium oxide to the X solution during stirring, fragrance, titanium oxide, anhydrous silicic acid (abrasive), sodium lauryl sulfate, coconut oil fatty acid amide propyl betaine solution, and polyoxyethylene hydrogenated castor oil are added. In addition, the mixture was further stirred under reduced pressure to obtain a dentifrice composition. A 1.5L kneader (manufactured by Ishiyama Kosakusho Co., Ltd.) was used for manufacturing.

Details of each component used in the preparation of the dentifrice composition are shown below, and the amount of each component used is shown in Table 1 below.
(A) Ingredient: Na pyrrolidone carboxylate (AJIDEW N-50 (manufactured by Ajinomoto Co., Inc.))
(B) Ingredient: Salt-isomerized amino acid (L-arginine C grade (manufactured by Ajinomoto Co., Inc.) or lysine hydrochloride (L-lysine hydrochloride (dietary) (manufactured by Ajinomoto Co., Inc.)))
(C) Ingredient: Water-soluble fluorine compound (sodium fluoride (purified sodium fluoride (S) RKX-32 (manufactured by Stella Chemifa)) or sodium monofluorophosphate (ICL Japan Ltd.))
(D) Ingredient: Zinc pyrrolidone carboxylate (AJIDEW ZN-100 (manufactured by Ajinomoto Co., Inc.))
As for other ingredients, those conforming to the quasi-drug raw material standard 2006 were used.

(Examples 1 to 25, Comparative Examples 1 to 11)
The components (A) to (D) were blended in the amounts shown in Tables 2 to 4, and the dentifrice composition was prepared by the method described in the above method for preparing a dentifrice composition. Various evaluation tests were carried out on the prepared dentifrice composition. The evaluation results are also shown in Tables 2-4.

From Tables 2 to 3, the oral composition of the present invention was excellent in the acid resistance effect of dentin and the decomposition suppressing effect of collagen (see Examples 1 to 25). Therefore, the oral composition of the present invention has an excellent preventive effect on dentin caries. In addition, the oral composition of the examples was evaluated for extrudability and no irritation in the oral cavity in order to evaluate usability. As a result, most of both evaluation results were "A", and it was confirmed that there was no problem in usability as a dentifrice composition.
When the blending amount of sodium pyrrolidone carboxylate or zinc pyrrolidone carboxylate is 10% (see Examples 5 and 20), the evaluation result of the extrudability is "B" or "C", but it is practically used. Is no problem.

On the other hand, as can be seen from Table 4, the oral composition containing no of the components (A) to (C) was inferior in the acid resistance effect of dentin (Comparative Examples 1 to 3). reference). Further, the oral composition containing no component (D) or containing zinc chloride or zinc citrate as an alternative component was inferior in the collagen decomposition inhibitory effect (see Comparative Examples 4 and 6 to 7). Further, the oral composition containing no two components (A) to (D) was inferior in at least one of the acid resistance effect of dentin and the collagen decomposition inhibitory effect (Comparative Example 5). , 8-11).

Claims (4)

(A) Ingredient: At least one of pyrrolidone carboxylic acid and its alkali metal salt,
(B) Ingredient: At least one of a basic amino acid and a salt thereof,
Component (C): Water-soluble fluorine compound and
(D) Ingredients: Zinc pyrrolidone carboxylate and
The alkali metal salt is a sodium or potassium salt and is
The basic amino acid is at least one selected from arginine, lysine, ornithine, and histidine.
The water-soluble fluorine compound is selected from sodium fluoride, potassium fluoride, ammonium fluoride, tin fluoride, amine fluoride, sodium monofluorophosphate, potassium monofluorophosphate, sodium silicon fluoride, and calcium silicon fluoride. At least one of them
The content of the component (A) is 0.1 to 10% by mass,
The content of the component (B) is 0.05 to 20% by mass,
The content of the component (C) is 0.01 to 0.5% by mass in terms of fluorine atoms.
The content of the component (D) is 0.1 to 10% by mass.
Oral composition. The oral composition according to claim 1 , wherein the component (B) is at least one selected from the group consisting of arginine, lysine, and salts thereof. The oral composition according to claim 1 or 2 , wherein the component (C) is sodium fluoride or sodium monofluorophosphate. The oral composition according to any one of claims 1 to 3, which is a dentifrice, a mouthwash, a coating agent, an oral pasta, a mouthwash, a chewing gum, a tablet confectionery, a candy, a gummies, a film, or a troche. thing.