JP7779709B2 - Oral composition - Google Patents

Description

The present invention relates to an oral composition.

Conventional dentifrice compositions have a pleasant taste and a refreshing sensation when used, which encourages continued use and promises improved effectiveness, but they are easily affected by the ingredients they contain. Enzymes, in particular, that have the ability to break down plaque are formulated as active ingredients in oral compositions because they are effective in preventing dental caries by breaking down plaque. However, when enzyme-containing toothpaste is used after being stored at high temperatures, there is a drawback in that, although there is no problem with its caries prevention effect, it has a distinctive bitter taste that significantly impairs the sensation of use, and improvements in this area have been sought.

Several methods for masking the harshness of enzymes using flavorings or base ingredients have been reported. Patent Document 1 describes how the combined harshness of dextranase, tranexamic acid, isopropylmethylphenol, and alkyl sulfates can be reduced by adding specific ratios of menthol, anethole, eugenol, and/or thyme oil to a dentifrice composition. Patent Document 2 also reports that the unpleasant taste of nonionic surfactants can be reduced while improving the stability of dextranase by adding specific ratios of sodium lauryl sulfate, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, and sodium bicarbonate to an oral composition containing dextranase.

Japanese Patent Application Laid-Open No. 2019-167297 Patent No. 5228380

However, the typical flavoring ingredients used in Patent Document 1 are highly volatile, and when the dentifrice composition is stored at high temperatures, the flavoring ingredients volatilize, which can result in insufficient bitterness reduction. Enzymes such as dextranase are particularly susceptible to temperature changes, and are prone to exhibiting a strong bitter flavor after high-temperature storage. Therefore, the oral composition of Patent Document 1 has the problem of insufficient bitterness reduction after high-temperature storage. Furthermore, the composition of Patent Document 2 also exhibits a strong bitter flavor derived from dextranase after high-temperature storage, calling for an improvement in the usability. In recent years, with the progress of global warming, temperatures often rise in warehouses during distribution, retail warehouses, and even during storage in the home, even near the bathroom sink, and there has been a demand for an improvement in the usability during high-temperature storage.

The object of the present invention is to suppress the occurrence of enzyme-induced discomfort in an enzyme-containing oral composition after high-temperature storage, and to achieve a sustained suppression effect.

The present inventors provide the following [1] to [11].
[1] An oral composition comprising: (A) component: one or more enzymes selected from the group consisting of polysaccharidases and proteases; and (B) component: one or more enzymes selected from N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethylcyclohexane-1-carboxamide, N-(4-cyanomethylphenyl)-2-isopropyl-5-methylcyclohexanecarboxamide, and N-(2-(2-pyridinyl)ethyl)-2-isopropyl-5-methylcyclohexanecarboxamide.
[2] The oral composition according to [1], wherein the polysaccharide-degrading enzyme is one or more enzymes selected from the group consisting of dextranase and mutanase.
[3] The oral composition according to [1] or [2], wherein the protease is one or more enzymes selected from the group consisting of papain, actinidin, and bromelain.
[4] The dentifrice composition according to any one of [1] to [3], wherein the amount of component (A) is 0.01 to 5.0% by mass.
[5] An oral composition according to any one of [1] to [4], wherein the amount of component (B) is 0.00001 to 0.1% by mass.
[6] An oral composition according to any one of [2] to [5], wherein the enzyme activity of dextranase is 10,000 to 14,000 units/g.
[7] The oral composition according to any one of [2] to [6], wherein the mutanase enzyme activity is 4,000 to 70,000 U/g.
[8] The oral composition according to any one of [3] to [7], wherein the papain has an enzyme activity of 200,000 to 2,500,000 units/g.
[9] The oral composition according to any one of [3] to [8], wherein the enzyme activity of actinidin is 9,000 to 210,000 units/g.
[10] The oral composition according to any one of [3] to [9], wherein the enzyme activity of bromelain is 300,000 to 500,000 units/g.
[11] The oral composition according to any one of [1] to [10], which is a dentifrice.

The present invention can suppress the occurrence of unpleasant sensations such as bitterness even after high-temperature storage (for example, storage at 30-40°C for 1-6 months), and the suppression effect can be sustained, thereby reducing the effort required for temperature control during logistics and storage and improving the usability.

[1. Oral composition]
The composition contains the following components (A) and (B):

1.1 Component (A): Enzyme
Component (A) is one or more enzymes selected from the group consisting of polysaccharide-degrading enzymes and proteases. By including component (A), the composition can be endowed with enzyme-derived functions.

-Polysaccharide degrading enzyme-
Polysaccharide-degrading enzymes are enzymes that hydrolyze the glycosidic bonds of polysaccharides to produce the constituent monosaccharides, oligosaccharides, or derivatives thereof. Examples of polysaccharides include dextran, mucin, cellulose, starch, chitin, agarose, carrageenan, heparin, alginic acid, hyaluronic acid, pectin, xylan, glucomannan, levan, glycogen, β-1,6-glucan, β-1,3-glucan, β-1,2-glucan, α-1,3-glucan, and α-1,2-glucan. Among these, polysaccharides involved in oral diseases (e.g., dental caries) are preferred, and polysaccharides contained in oral biofilms (e.g., dental plaque), such as dextran and mucin, are more preferred. Examples of polysaccharide-degrading enzymes include dextranase, mutanase, α-amylase, β-amylase, pullulanase, glucoamylase, α-glucosidase, isoamylase, cellulase (including β-glucanase), and hemicellulase, with dextranase and mutanase being preferred. These enzymes degrade polysaccharides such as dextran and mutan contained in oral biofilms (e.g., dental plaque), thereby inhibiting and preventing the progression of dental caries in the oral cavity. The origin of the enzyme is not particularly limited, and it may be naturally derived from microorganisms, plants, animals, etc., or may be artificially prepared by genetic recombination, chemical synthesis, etc. When the polysaccharide-degrading enzyme is dextranase, it may be derived from bacteria capable of producing dextranase (e.g., bacteria of the genera Chaetomium, Penicillium, Aspergillus, Spicaria, Lactobacillus, and Cellvibrio). When the polysaccharide-degrading enzyme is mutanase, it may be a mutanase derived from a bacterium capable of producing mutanase (for example, the genus Probetella or Paenibacillus). One type of polysaccharide-degrading enzyme may be used alone, or two or more types may be used in combination.

-Proteolytic enzymes-
Proteases are enzymes that catalyze the hydrolysis of peptide bonds in proteins. Proteases may be either endopeptidases or exopeptidases (aminopeptidases, carboxypeptidases), with endopeptidases being preferred. Examples of endoproteases include cysteine proteases such as papain, bromelain, and actinidin, and serine proteases such as nattokinase. Cysteine proteases are preferred, with papain, bromelain, and actinidin being more preferred, and papain being even more preferred. This allows the enzyme to decompose proteins present in oral biofilms (e.g., tongue coating) and exhibit oral biofilm removal effects. The origin of the enzyme is not particularly limited, and it may be naturally derived from microorganisms, plants, animals, etc., or artificially prepared by genetic recombination, chemical synthesis, etc. Papain can be derived from papaya (Carica papaya) fruit, actinidin can be derived from kiwi (Actinidia deliciosa) fruit, bromelain can be derived from pineapple (Ananas comosus) fruit or rhizome, and nattokinase can be derived from Bacillus natto. Examples of protease include proteases produced by bacteria belonging to the Aspergillus and Bacillus genera. One protease may be used alone, or two or more may be used in combination.

-Enzyme activity-
The enzymatic activity (enzyme titer) of the polysaccharide-degrading enzyme and the protease is not particularly limited and can be appropriately selected depending on the type of enzyme. Examples are as follows:
The enzymatic activity of dextranase (per gram of enzyme, the same applies hereinafter) is preferably 10,000 to 14,000 U/g, more preferably 11,000 to 13,000 U/g, even more preferably 11,500 to 12,500 U/g, and even more preferably about 12,000 U/g. The enzymatic activity of mutanase is preferably 4,000 to 70,000 U/g, more preferably 5,000 to 10,000 U/g, even more preferably 5,500 to 8,000 U/g, and even more preferably about 6,000 U/g. The enzymatic activity of papain is preferably 200,000 to 2,500,000 U/g, more preferably 500,000 to 1,000,000 U/g, even more preferably 600,000 to 900,000 U/g, and even more preferably about 800,000 U/g. The enzymatic activity of actinidin is preferably 9,000 to 210,000 U/g, more preferably 50,000 to 200,000 U/g, even more preferably 100,000 to 190,000 U/g, and even more preferably about 180,000 U/g. The enzymatic activity of bromelain is preferably 300,000 to 500,000 U/g, more preferably 350,000 to 450,000 U/g, even more preferably 380,000 to 420,000 U/g, and even more preferably about 400,000 U/g.
By setting the enzymatic activity of each enzyme within the above numerical range, the desired function of the enzyme can be exhibited well, and the unpleasant feeling (e.g., bitterness) of the oral composition caused by the enzyme-derived component (A) after high-temperature storage can be reduced by the component (B).

In terms of enzyme activity, one unit is defined as "the amount of enzyme that can convert 1 μmol of substrate in 1 minute at 30°C in 1 L of sample under optimal conditions," based on the 1964 definition of "International Units" by the International Union of Biochemistry (see https://www.jslm.org/committees/standard/standard_Q&A.pdf).

The enzymatic activity of each enzyme can be defined according to standard methods. For example, one unit of enzymatic activity for dextranase or mutanase can be defined as the amount of each enzyme that produces free reducing sugars equivalent to 1 μmol of glucose per minute when reacted at 40°C and pH 5 using dextran or mutan, respectively, as substrates. One unit of enzymatic activity for papain, actinidin, and bromelain can be measured according to the Japanese Standards for Food Additives. Specifically, it is the amount of each enzyme that produces amino acids equivalent to 1 μg of tyrosine per minute using casein as a substrate. In the above measurement methods, the amount of enzyme can also be measured according to standard methods, and absorbance, etc., can be used. One unit of enzymatic activity for nattokinase can be defined as the amount of enzyme that increases the absorbance (275 nm) of fibrin degradation products by 0.01 per minute using fibrin as a substrate (U).

Component (A) may be a polysaccharide-degrading enzyme, a protease, or a combination thereof, with polysaccharide-degrading enzymes being preferred and dextranase being more preferred.

-Content of component (A)-
The content of component (A) may be appropriately determined within the range of the effective amount of the enzyme. From the viewpoint of the effects of the present invention, however, the following applies. The lower limit is typically 0.01% by mass or more, preferably 0.05% by mass or more, and more preferably 0.07% by mass or more. This allows the oral composition to contain an effective amount of the enzyme, thereby enabling the desired function of the enzyme to be satisfactorily exhibited. The upper limit of the content of component (A) is typically 5.0% by mass or less, preferably 3.0% by mass or less, and more preferably 1.0% by mass or less. This allows component (B) to reduce the unpleasant sensation (e.g., bitterness) of the oral composition caused by the enzyme from component (A) after high-temperature storage. Therefore, the content of component (A) is preferably 0.01 to 5.0% by mass of the entire composition, preferably 0.05 to 3.0% by mass, and more preferably 0.07 to 1.0% by mass. The content of component (A) refers to the content of each enzyme constituting component (A). When component (A) is dextranase (12,000 units/g product) and mutanase (6,000 units/g product), if the content of each enzyme as component (A) is within the above range, a good plaque decomposition effect can be achieved.

1.2 Component (B): Cooling agent
Component (B) is one or more selected from N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethylcyclohexane-1-carboxamide (molecular weight 316), N-(4-cyanomethylphenyl)-2-isopropyl-5-methylcyclohexanecarboxamide (molecular weight 298), and N-(2-(2-pyridinyl)ethyl)-2-isopropyl-5-methylcyclohexanecarboxamide (molecular weight 288). These cooling sensation agents have larger molecular weights than typical fragrance components, and therefore volatilize in small amounts from the composition even during high-temperature storage. Therefore, by including component (B), the discomfort caused by component (A) after high-temperature storage can be suppressed, and the suppression effect can be maintained.

Component (B) may be a single compound or a combination of two or more compounds, but it preferably contains N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethylcyclohexane-1-carboxamide, and more preferably consists solely of N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethylcyclohexane-1-carboxamide. This helps to reduce irritation to the oral cavity.

-Content of component (B)-
The content of component (B) is typically 0.000001% by mass or more of the total composition, preferably 0.00001% by mass or more, and more preferably 0.00005% by mass or more. This allows for the suppression of discomfort caused by component (A) after high-temperature storage, and the suppression effect can be maintained even after use. The upper limit is typically 0.5% by mass or less of the total composition, preferably 0.1% by mass or less, and more preferably 0.05% by mass or less. This allows for the suppression of oral irritation caused by component (B). Therefore, the content of component (B) is typically 0.000001 to 0.5% by mass of the total composition, preferably 0.00001 to 0.1% by mass, and more preferably 0.00005 to 0.05% by mass.

[1.3 Optional components]
The oral composition may contain components other than the components (A) and (B) to the extent that the effects of the present invention are not impaired.

Optional ingredients include, for example, ingredients commonly used in oral compositions, such as abrasives, medicinal ingredients, surfactants, binders, humectants, thickeners, sweeteners, preservatives, pH adjusters, solvents, oily ingredients, colorants (pigments), and fragrances. These are explained in detail below.

-Abrasives-
The abrasive may be either an inorganic abrasive or an organic abrasive. Examples of inorganic abrasives include abrasive silica such as precipitated silica, aluminosilicate, zirconosilicate, crystalline zirconium silicate, and titanium-bonded silica; calcium phosphate compounds such as dibasic calcium phosphate dihydrate or anhydrous calcium phosphate, monobasic calcium phosphate, tribasic calcium phosphate, and calcium pyrophosphate; calcium carbonate abrasives such as calcium carbonate; calcium abrasives other than carbonate/phosphate such as calcium hydroxide and calcium sulfate; aluminum materials such as aluminum oxide, aluminum hydroxide, and alumina; silicic acid materials such as anhydrous silicic acid, zeolite, and zirconium silicate; magnesium materials such as magnesium carbonate and tribasic magnesium phosphate; apatite materials such as hydroxyapatite, fluoroapatite, and calcium-deficient apatite; titanium materials such as titanium dioxide, titanium mica, and titanium oxide; and minerals such as bentonite. Examples of organic abrasives include polymethyl methacrylate and synthetic resin abrasives. Among these, silica abrasives are preferred.

The abrasive content is typically 70% by mass or less, preferably 50% by mass or less, and more preferably 8 to 50% by mass, based on the total oral composition (100% by mass).

-Medicinal ingredients-
Examples of medicinal ingredients include bactericidal or antibacterial agents such as cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, isopropylmethylphenol, zinc gluconate, zinc citrate, triclosan, thymol, hinokitiol, and lysozyme chloride; enzymes other than component (A) such as amylase and Liteque Enzyme; fluorides such as sodium fluoride, sodium monofluorophosphate, and stannous fluoride; ε-aminocaproic acid, allantoin, tranexamic acid, glycyrrhizinate (e.g., dipotassium glycyrrhizinate), glycyrrhetinic acid, glycyrrhetinic acid derivatives (e.g., stearyl glycyrrhetinate), allantoin chlorohydroxyaluminum, azulene, and dihydrocholesterol. Examples of medicinal ingredients include anti-inflammatory agents such as chloral, zinc salts, copper salts, and tin salts; metal salts such as zinc salts, copper salts, and tin salts; anti-tartar agents such as condensed phosphates and ethanehydroxydiphosphonate; blood flow promoters such as vitamin E (e.g., tocopherol acetate); dentin hypersensitivity inhibitors such as potassium nitrate, aluminum lactate, and strontium chloride; coating agents such as hydroxyethylcellulose dimethyldiallylammonium chloride; astringents such as vitamin C (e.g., ascorbic acid or its salt), lysozyme chloride, and sodium chloride; water-soluble copper compounds such as copper chlorophyll and copper gluconate; amino acids such as alanine, glycine, and proline; plant extracts such as thyme, Scutellaria Root, clove, and witch hazel; callopeptides; and polyvinylpyrrolidone. These may be used alone or in combination of two or more. The content of the medicinal ingredients can be appropriately determined in an effective amount according to conventional methods.

-Surfactant-
The optional surfactants are anionic surfactants, nonionic surfactants, and amphoteric surfactants.

Examples of anionic surfactants include alkyl sulfates, acylamino acid salts, acyltaurine salts, α-olefin sulfonates, hydrogenated coconut fatty acid monoglyceride monosulfate, and lauryl sulfoacetate. The alkyl and acyl groups may be straight-chain or branched, saturated or unsaturated, and typically contain 10 to 20 carbon atoms, preferably 12 to 18, and more preferably 12 to 14. Salts can be selected from pharmacologically acceptable salts. Examples of pharmacologically acceptable salts include base addition salts and amino acid salts. Specific examples include inorganic base salts such as sodium salts, potassium salts, calcium salts, magnesium salts, and ammonium salts; organic base salts such as triethylammonium salts, triethanolammonium salts, pyridinium salts, and diisopropylammonium salts; and basic amino acid salts such as arginine salts. Among these, inorganic base salts are preferred, with alkali metal salts (e.g., sodium salts and potassium salts) or ammonium salts being more preferred, and sodium salts being even more preferred.

Examples of alkyl sulfates include lauryl sulfate (e.g., sodium lauryl sulfate) and myristyl sulfate. Examples of acylamino acid salts include acyl glutamates such as lauroyl glutamate, myristoyl glutamate, and palmitoyl glutamate; acyl glycine salts such as N-lauroyl-N-methyl glycine and cocoyl glycine; acyl alanine salts such as N-lauroyl-β-alanine, N-myristyl-β-alanine, N-cocoyl-β-alanine, N-lauroyl-N-methyl-β-alanine, N-myristoyl-N-methyl-β-alanine, and N-methyl-N-acylalanine; and acyl aspartates such as lauroyl aspartate. Examples of acyltaurine salts include lauroyl methyl taurine, N-methyl-N-acyltaurine, and N-cocoyl methyl taurine. Examples of α-olefin sulfonates include α-olefin sulfonates having 12 to 18 carbon atoms, such as tetradecene sulfonate. Other examples of anionic surfactants include hydrogenated coconut fatty acid monoglyceride sodium monosulfate and sodium lauryl sulfoacetate.

From the standpoint of foaming ability and foam quality, the anionic surfactant preferably contains a sulfonic acid group, with α-olefin sulfonate, alkyl sulfate, lauryl sulfate, and tradecene sulfonate being more preferred. The content of the anionic surfactant is preferably 0.1 to 2.5% by mass, more preferably 0.6 to 2.5% by mass, and even more preferably 1 to 2.5% by mass of the entire oral composition.

Examples of nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters (e.g., polyoxyethylene sorbitan monostearate), alkylolamides, polyoxyethylene fatty acid esters, polyoxyethylene alkenyl ethers, glycerin fatty acid esters, sucrose fatty acid esters (e.g., maltose fatty acid esters), sugar alcohol fatty acid esters (e.g., maltitol fatty acid esters, lactitol fatty acid esters), fatty acid diethanolamides (e.g., lauric acid mono- or diethanolamide), polyoxyethylene polyoxypropylene copolymers, and polyoxyethylene polyoxypropylene fatty acid esters. The alkyl chain of the polyoxyethylene alkyl ether typically has 14 to 18 carbon atoms, and the average number of moles of ethylene oxide added is typically 5 to 30 moles. The average number of moles of ethylene oxide added of polyoxyethylene hydrogenated castor oil is typically 20 to 100 moles, preferably 20 to 60 moles. The fatty acid of the sorbitan fatty acid ester typically has 12 to 18 carbon atoms. The number of carbon atoms in the fatty acid of the polyoxyethylene sorbitan fatty acid ester is typically 16 to 18, and the average number of moles of ethylene oxide added is typically 10 to 40. The number of carbon atoms in the alkyl chain of the alkylolamide is typically 12 to 14. Preferred nonionic surfactants are polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene alkyl ether.

Examples of amphoteric surfactants include betaine-type amphoteric surfactants such as alkyldimethylaminoacetic acid betaines (e.g., lauryldimethylaminoacetic acid betaine) and fatty acid amidopropyldimethylaminoacetic acid betaines (e.g., cocamidopropyl betaine); imidazoline-type amphoteric surfactants such as N-fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine salts (e.g., N-coconut fatty acid acyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine), coconut fatty acid imidazolinium betaine, and 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine; and alkyl betaines such as lauryldimethylaminoacetic acid betaine. Examples of cationic surfactants include alkylammonium salts and alkylbenzylammonium salts. The content of the amphoteric surfactant is preferably 0.1 to 2% by mass, more preferably 0.2 to 1.5% by mass, and even more preferably 0.3 to 1% by mass of the total oral composition.

The surfactant content is typically 3% by mass or less, preferably 2% by mass or less, more preferably 0.1 to 3% by mass, and even more preferably 0.3 to 2% by mass, based on the total oral composition (100% by mass).

- Wetting agent -
Examples of humectants include sugar alcohols and polyhydric alcohols other than sugar alcohols. Examples of sugar alcohols include sorbitol (sorbitol), erythritol, maltitol, lactitol, and xylitol. Examples of polyhydric alcohols other than sugar alcohols include glycerin; glycols such as ethylene glycol, propylene glycol, dipropylene glycol, butylene glycol, and polyethylene glycol (PEG); and reduced starch saccharification products. Examples of polyethylene glycols include those with an average molecular weight of 150 to 6,000, and those with an average molecular weight of 190 to 630 (PEG200, PEG300, PEG400, and PEG600). The average molecular weight is the average molecular weight specified in the Quasi-drug Raw Materials Standards 2006. The content of the humectant is typically 40% by weight or less, preferably 1 to 35% by weight, based on the total oral composition (100% by weight).

The content of the humectant is typically 40% by mass or less, and preferably 1 to 30% by mass, of the total oral composition (100% by mass).

- Binder -
Examples of the binder include any suitable conventional organic binder, such as polysaccharides, cellulose-based binders (e.g., carboxymethyl cellulose (CMC), hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, cationized cellulose, etc.), other polysaccharide thickeners (e.g., xanthan gum, guar gum, gellan gum, tragacanth gum, karaya gum, gum arabic, locust bean gum, carrageenan, sodium alginate), and synthetic water-soluble polymers (e.g., sodium polyacrylate, carboxyvinyl polymer, polyvinylpyrrolidone, polyvinyl alcohol, propylene glycol alginate). Furthermore, inorganic binders such as thickening silica and aluminum silicate may also be contained.

The organic binder content is preferably 0 to 3% by mass, and more preferably 0.1 to 2% by mass, of the total oral composition (100% by mass). The inorganic binder content is preferably 0 to 10% by mass, and more preferably 1 to 8% by mass.

-Sweetener-
Examples of sweeteners include xylitol, erythritol, maltitol, saccharin, saccharin sodium, aspartame, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidin dihydrochalcone, perillartine, glycyrrhizin, thaumatin, and aspartylphenylalanine methyl ester. The sweeteners may be used singly or in combination of two or more of the above-listed sweeteners.

- Preservatives -
Examples of preservatives include parahydroxybenzoic acid esters (e.g., methyl parahydroxybenzoate, ethyl parahydroxybenzoate, and butyl parahydroxybenzoate) and sodium benzoate. The preservatives may be used alone or in combination of two or more.

- pH adjuster -
Examples of pH adjusters include organic acids such as phthalic acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid, and lactic acid, or their salts (sodium citrate), inorganic acids such as phosphoric acid (orthophosphoric acid), or their salts (e.g., potassium salts, sodium salts, and ammonium salts), and hydroxides such as sodium hydroxide and potassium hydroxide. Examples of inorganic acid salts include disodium hydrogen phosphate and sodium dihydrogen phosphate.

The amount of pH adjuster contained is typically such that the pH of the oral composition after addition is preferably 5 to 9, more preferably 6 to 8.5.

In this specification, the pH value typically refers to the value measured at 25°C and 3 minutes after the start of measurement. The pH value can be measured, for example, using a pH meter (model number Hm-30S) manufactured by Toa Denpa Kogyo Co., Ltd.

-solvent-
Examples of the solvent include water (purified water) and ethanol, with water being preferred. The amount of the solvent is not particularly limited, but the water content of the solvent is preferably more than 2% by mass. The solvent may be used alone or in combination of two or more.

-Oil-based ingredients-
Examples of oily components include hydrocarbons such as squalane, liquid paraffin, petrolatum, and microcrystalline wax; higher alcohols (e.g., alcohols having 8 to 22 carbon atoms such as lauryl alcohol, cetyl alcohol, cetostearyl alcohol, oleyl alcohol, and isostearyl alcohol); higher fatty acids (e.g., fatty acids having 8 to 22 carbon atoms such as lauric acid, myristic acid, oleic acid, and isostearic acid), vegetable oils such as olive oil, castor oil, and coconut oil; and fatty acid esters such as isopropyl myristate.

- Coloring agent -
Examples of colorants include natural dyes such as safflower red pigment, gardenia yellow pigment, gardenia blue pigment, perilla pigment, red koji pigment, red cabbage pigment, carrot pigment, hibiscus pigment, cocoa pigment, spirulina blue pigment, and tamarind pigment, as well as legally designated dyes such as Red No. 2, Red No. 3, Red No. 104, Red No. 105, Red No. 106, Red No. 227, Yellow No. 4, Yellow No. 5, Green No. 3, and Blue No. 1, riboflavin, sodium copper chlorophine, and titanium dioxide. When the oral composition contains a colorant, the content thereof is preferably 0.00001 to 3% by mass of the entire oral composition.

-Fragrance-
By including a fragrance in the composition, the feeling during use can be further improved. Examples of fragrances include natural fragrances such as eucalyptus oil, wintergreen oil, cassia oil, sage oil, lemon oil, orange oil, cardamom oil, coriander oil, mandarin oil, lime oil, lavender oil, rosemary oil, laurel oil, chamomile oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie oil, yuzu oil, iris concrete, absolute rose, and orange flower; fragrances obtained by processing these natural fragrances (e.g., front-end cutting, back-end cutting, fractional distillation, liquid-liquid extraction, essence formation, powdered fragrance formation); and menthol, anethole, eugenol, carvone, cineole, methyl salicylate, cinnamic aldehyde, 3-l-menthoxypropane-1,2-diol, linalool, linalyl azalea ...methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl salicylate, methyl Examples of the flavoring agent include single flavoring agents such as acetate, limonene, menthone, menthyl acetate, pinene, octyl aldehyde, citral, pulegone, carbeyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methylphenylglycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cyclotene, furfural, trimethylpyrazine, ethyl lactate, and ethyl thioacetate, as well as blended flavoring agents such as strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, and tropical fruit flavor. Among these, mint flavoring agents (e.g., menthol, anethole, eugenol, and blended flavoring agents containing these) are preferred. As the fragrance, the fragrances exemplified above may be used alone or in combination of two or more, as long as the effects of the present invention are not impaired.
The above-mentioned fragrance materials are preferably used in an amount of 0.000001 to 2% in the composition, and fragrances using the above-mentioned fragrance materials are preferably used in an amount of 0.1 to 2% in the composition.

-Other optional ingredients-
Examples of optional components other than those mentioned above include polyisobutylene, polybutadiene, urethane, silicone, and natural rubber. The content of these optional components can be appropriately set within a range that does not impair the effects of the present invention.

2. Dosage form and use of the composition
The oral composition can be prepared as an oral preparation such as a dentifrice, mouthwash, spray, liniment, patch, or oral dissolving agent. The dosage form of the oral composition can be appropriately selected depending on the form of use and is not particularly limited. For example, the dosage form may be a paste, liquid, or the like, and in the case of a dentifrice, it can be prepared as a toothpaste, gel toothpaste, liquid toothpaste, liquid toothpaste, or lubricant toothpaste.

3. Method for producing the composition
The method for producing the oral composition is not particularly limited, and it can be prepared by any conventional method depending on the dosage form. For example, when used as a toothpaste, a method can be used in which the components soluble in a solvent are prepared, and then the other insoluble components are mixed, and degassing (e.g., reduced pressure, etc.) is performed as necessary. The obtained toothpaste can be placed in a container to make a product. The shape and material of the container are not particularly limited, and containers used for conventional toothpaste compositions can be used, such as containers such as laminated tubes made of plastics such as polyethylene, polypropylene, polyethylene terephthalate, and nylon.

The present invention will be explained in detail below using examples and comparative examples, but the present invention is not limited to the following examples. Note that % in the tables indicates % by mass unless otherwise specified.

[Components used in Examples and Comparative Examples]
-Component (A)-
A-1: Dextranase (enzyme activity 12,000 U/g, manufacturer: Daiichi Sankyo Propharma Co., Ltd.)
A-2: Mutanase (enzyme activity 6,000 U/g, manufacturer: Amano Enzyme Co., Ltd.)
A-3: Actinidin (trade name: Actinase, enzyme activity 180,000 units/g, manufacturer: BHN Corporation)
A-4: Papain (product name: purified papain, enzyme activity 800,000 U/g, manufacturer: Mitsubishi Chemical Foods Corporation)
A-5: Bromelain (product name: Bromelain (enzyme activity 400,000 U/g), manufacturer: Godo Shusei Co., Ltd.)

-Component (B) and its substitutes-
B-1: N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethylcyclohexane-1-carboxamide (trade name: CA370, molecular weight 316, manufacturer: Takasago International Corporation)
B-2: N-(4-cyanomethylphenyl)-2-isopropyl-5-methylcyclohexanecarboxamide (trade name: Evercool 180, molecular weight 298, manufacturer: Givaudan)
B-3: N-(2-(2-pyridinyl)ethyl)-2-isopropyl-5-methylcyclohexanecarboxamide (trade name: Evercool 190, molecular weight 288, manufacturer: Givaudan)
B-4 (alternative component): N-ethyl-p-menthane-3-carboxamide (trade name: WS-3, molecular weight 211.35, manufacturer: Symrise Japan Co., Ltd.)

-Optional ingredients-
Abrasive silica (trade name: Tixosil (registered trademark) 73, manufacturer: Solvay)
Sodium fluoride (Manufacturer: Stella Chemifa Corporation)
Sodium lauryl sulfate (manufacturer: BASF)
Sorbitol solution (70%) (manufacturer: Mitsubishi Corporation Life Sciences Co., Ltd.)
Propylene glycol (manufacturer: ADEKA)
Xanthan gum (product name: Monart Gum DA, manufacturer: CP Chemicals)
Viscosity-increasing silica (product name: Carplex (registered trademark) #67, manufacturer: DSL Japan Co., Ltd.)
Saccharin sodium (manufacturer: Aisan Chemical Industry Co., Ltd.)
Mint flavor (contains 50% menthol)

Examples 1 to 19 and Comparative Examples 1 to 6
Dentifrice compositions having the compositions shown in Tables 1 to 5 were prepared by conventional methods. The resulting dentifrice compositions were used as samples and evaluated by the following methods. The results are also shown in the tables.

<Evaluation method>
After storing each dentifrice composition at 40°C for one month, four expert flavor panelists evaluated the dentifrice composition's usability. One gram of sample dentifrice composition was placed on a toothbrush (Clinica Advantage Toothbrush, 4-row compact regular type, manufactured by Lion Corporation) and the patient brushed their teeth for three minutes. The refreshing sensation at the start of brushing, the lack of bitterness during use, and the persistence of the lack of bitterness after rinsing were each judged according to the rating scale shown below, and evaluated according to the following evaluation criteria.
Furthermore, those rated as ◯ or better were judged to be dentifrice compositions with reduced bitterness, a pleasant taste, and a refreshing, non-irritating feel when used.

<Lack of bitterness when using products stored at high temperatures>
Regarding the lack of bitterness, we evaluated whether or not the subject felt any bitterness while brushing their teeth.
(Rating criteria)
4 points: No bitterness felt 3 points: Almost no bitterness felt 2 points: Bitterness felt 1 point: Strong bitterness felt (rating criteria)
◎: 3-4 out of 4 people scored 4 points, 0-1 person scored 3 points, and 0 people scored 2 points or less. ○: 0-2 out of 4 people scored 4 points, 2-4 people scored 3 points, and 0 people scored 2 points or less. △: 1-3 out of 4 people scored 2 points or less. ×: 4 out of 4 people scored 2 points or less.

<Maintains a lack of bitterness when stored at high temperatures>
To evaluate the duration of the astringency, subjects brushed their teeth for 3 minutes in the same manner as in the astringency test, and evaluated the time during which they were not astringent after rinsing.
(Rating criteria)
4 points: 25 minutes or more (no bitterness felt)
3 points: 15 minutes or more but less than 25 minutes 2 points: 5 minutes or more but less than 15 minutes 1 point: Less than 5 minutes (rating criteria)
◎: 3-4 out of 4 people scored 4 points, 0-1 person scored 3 points, and 0 people scored 2 points or less. ○: 0-2 out of 4 people scored 4 points, 2-4 people scored 3 points, and 0 people scored 2 points or less. △: 1-3 out of 4 people scored 2 points or less. ×: 4 out of 4 people scored 2 points or less.

＜Lack of stimulation＞
Regarding the lack of irritation, subjects brushed their teeth for 3 minutes in the same manner as in the test for lack of astringency, and evaluated whether they felt any irritation while brushing their teeth.
(Rating criteria)
4 points: No irritation felt 3 points: Almost no irritation felt 2 points: Irritation felt 1 point: Strong irritation felt (rating criteria)
◎: 3-4 out of 4 people scored 4 points, 0-1 person scored 3 points, and 0 people scored 2 points or less. ○: 0-2 out of 4 people scored 4 points, 2-4 people scored 3 points, and 0 people scored 2 points or less. △: 1-3 out of 4 people scored 2 points or less. ×: 4 out of 4 people scored 2 points or less.

Comparative Examples 1 to 5, which used high-temperature storage products containing component (A) but not component (B), and Comparative Example 6, which used a high-temperature storage product containing component (A) and comparative component (B-4), exhibited a bitter taste even during use. In contrast, Examples 1 to 19, which used high-temperature storage products containing components (A) and (B), all exhibited sufficient bitterness-suppressing and plaque-decomposing properties, did not cause any irritation in the oral cavity, and provided good bitterness suppression and sustained effect after spitting out.

Claims (8)

(A) component: one or more enzymes selected from the group consisting of polysaccharide-degrading enzymes and proteases; and (B) component: one or more enzymes selected from N-(2-hydroxy-2-phenylethyl)-2-isopropyl-5,5-dimethylcyclohexane-1-carboxamide, N-(4-cyanomethylphenyl)-2-isopropyl-5-methylcyclohexanecarboxamide, and N-(2-(2-pyridinyl)ethyl)-2-isopropyl-5-methylcyclohexanecarboxamide ,
the polysaccharide-degrading enzyme is one or more selected from the group consisting of dextranase and mutanase;
the protease is one or more selected from the group consisting of papain, actinidin, and bromelain;
The amount of component (B) is 0.00001 to 0.005% by mass.
Oral composition. 2. The oral composition according to claim 1 , wherein the amount of component (A) is 0.01 to 5.0% by mass. The component (A) contains dextranase,
3. The oral composition according to claim 1 , wherein the enzyme activity of dextranase is 10,000 to 14,000 units/g. The component (A) contains mutanase,
3. The oral composition according to claim 1 , wherein the mutanase has an enzyme activity of 4,000 to 70,000 U/g. The component (A) contains papain,
3. The oral composition according to claim 1 , wherein the papain has an enzyme activity of 200,000 to 2,500,000 units/g. The component (A) contains actinidin,
The enzyme activity of actinidin is 9,000 to 210,000 units/g.1 or 2The oral composition described above. The component (A) contains bromelain,
3. The oral composition according to claim 1 , wherein the enzyme activity of bromelain is 300,000 to 500,000 units/g. The oral composition according to any one of claims 1 to 7 , which is a dentifrice.