Composition for oral cavity

Abstract

A composition for an oral cavity according to one embodiment of the present invention comprises: a component (A), which is at least one selected from the group consisting of berberine, a salt thereof, a plant containing berberine or a salt thereof, and an extract of the plant; and a component (B), which is sodium tetradecenesulfonate, wherein, when the mass of the component (A) in terms of berberine is A and the mass of the component (B) is B, the ratio B / A is 20-200.

Description

Oral composition

[0001] The present invention relates to an oral composition. This application claims priority to Japanese Patent Application No. 2023-103232, filed on June 23, 2023, the contents of which are incorporated herein by reference.

[0002] Many bacteria coexist symbiotically in the human body. These bacteria form a bacterial community known as the microbiota, which plays an important role in maintaining human health. This microbiota is a mixture of non-pathogenic resident bacteria and pathogenic bacteria, including opportunistic pathogens (hereinafter referred to as "pathogenic bacteria"). However, the bacterial composition of the microbiota is normally balanced in a healthy state, suppressing diseases caused by pathogenic bacteria. Although the bacterial composition of the microbiota varies from body part to body, internal or external factors can disrupt the balance of the bacterial composition and disrupt homeostasis, allowing pathogenic bacteria to dominate and leading to disease. Therefore, to maintain and improve health, it is important not only to maintain homeostasis of the bacterial composition but also to suppress only pathogenic bacteria and create a microbiota that is less susceptible to disruption of homeostasis, allowing non-pathogenic resident bacteria to dominate.

[0003] Oral diseases such as dental caries and periodontal disease in the oral cavity also develop and progress when the homeostasis of the oral bacterial flora is disrupted and pathogenic bacteria become dominant. Pathogenic bacteria include Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum, which cause periodontal disease and bad breath, and Streptococcus mutans, which causes dental caries. Therefore, in order to suppress the onset and progression of oral diseases, it is important not only to suppress pathogenic bacteria but also to maintain a healthy balance of bacteria that make up the oral flora.

[0004] On the other hand, berberine and its salts are known to have antibacterial properties that inhibit the growth of pathogenic bacteria. Patent Document 1 describes that the combined use of two antibacterial agents, including berberine, provides higher antibacterial activity (lower MIC) against oral pathogenic bacteria such as Porphyromonas gingivalis compared to the use of one antibacterial agent alone.

[0005] Japan Special Table No. 2000-514834

[0006] However, according to the studies of the present inventors, when berberine or its salt is simply added to oral compositions such as dentifrice compositions and mouthwash compositions, the effect of reducing the ratio of pathogenic bacteria to the total number of oral bacteria (selective antibacterial effect) may be insufficient. The present invention has been made in view of the above circumstances, and aims to provide an oral composition having excellent selective antibacterial effect against pathogenic bacteria in the oral cavity.

[0007] The present invention has the following aspects: [1] An oral composition comprising: (A) component: at least one selected from the group consisting of berberine, its salts, plants containing berberine or its salts, and extracts thereof; and (B) component: sodium tetradecene sulfonate, wherein, when the mass of the component (A) converted to berberine is A and the mass of the component (B) is B, the ratio of B / A is 20 to 200. [2] The oral composition according to [1], further comprising: (C) component: a nonionic surfactant, wherein, when the mass of the component (C) is C, the ratio of C / A is 100 to 2500, and the ratio of C / B is 1 to 50. [3] The oral composition according to [2], wherein the component (C) is at least one selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, sorbitan fatty acid ester, and polyglycerin fatty acid ester. [4] The oral composition according to any one of [1] to [3], which is used for improving oral bacterial flora.

[0008] According to the present invention, an oral composition having excellent selective antibacterial activity against pathogenic bacteria in the oral cavity can be provided.

[0009] An oral composition according to one embodiment of the present invention comprises component (A) and component (B). The oral composition may further comprise component (C). The oral composition may further comprise components other than component (A), component (B), and component (C).

[0010] <Component (A)> Component (A) is at least one selected from the group consisting of berberine, its salts, plants containing berberine or its salts, and extracts thereof. Berberine and its salts have selective antibacterial activity against pathogenic bacteria in the oral cavity. Specifically, they can selectively inhibit the growth of pathogenic bacteria among oral bacteria and reduce the ratio of the number of pathogenic bacteria to the total number of oral bacteria.

[0011] Examples of berberine salts include berberine chloride, berberine sulfate, and berberine tannate. Berberine chloride is preferred in terms of storage stability of the oral composition. Berberine chloride may be a hydrate. Berberine chloride hydrate, listed in the 18th Edition of the Japanese Pharmacopoeia, can be used as the berberine chloride hydrate. Examples of plants containing berberine or its salts include Rutaceae plants such as Phellodendron bark (Phellodendron bark), Ranunculaceae plants such as Coptis chinensis, Goldenseal, and Origanum sativum, and Berberidaceae plants such as Oregon grape. Plant extracts may be in liquid form or solid form such as powder. Known plant extracts can be used, including solvent extracts and their dried products. Examples of extraction solvents include hydrophilic solvents such as water, lower monohydric alcohols such as ethanol and propanol, and polyhydric alcohols such as 1,3-butylene glycol and propylene glycol. A single solvent selected from these or a mixture of two or more solvents can be used. Water and ethanol are preferred, with water, particularly hot water, being preferred. Conventional extraction conditions and post-treatment methods can be used. Commercially available plant extracts can be used, such as those available under the trade names Phellodendron Bark Extract from Ogi Pharmaceutical Co., Ltd. and Coptis Rhizome Extract from Alps Pharmaceutical Co., Ltd. One type of component (A) can be used alone, or two or more types can be used in combination.

[0012] In terms of storage stability of the oral composition, component (A) is preferably at least one selected from the group consisting of Phellodendron bark and Phellodendron bark extract. Phellodendron bark powder listed in the 18th Revised Japanese Pharmacopoeia can be used as Phellodendron bark. Phellodendron bark extract may be in liquid form or in a dried solid form. Phellodendron bark extract listed in the Quasi-drug Raw Materials Standards 2021 can be used as the Phellodendron bark extract. Commercially available products of these products can also be used. Examples of commercially available products include Phellodendron bark extract S (manufactured by Ogi Pharmaceutical Co., Ltd.), which is a powdered extract obtained by hot water extraction of Phellodendron bark and spray drying it, and Phellodendron bark extract liquid-J (manufactured by Maruzen Pharmaceutical Co., Ltd.), which is a liquid extract containing ethanol.

[0013] In addition, in the 18th edition of the Japanese Pharmacopoeia, berberine chloride hydrate is determined as follows: ２０ H １８ ClNO ４ In the 18th edition of the Japanese Pharmacopoeia, Phellodendron Bark Powder is a powder of Phellodendron Bark. When quantifying this product, the amount of berberine [berberine chloride (C)] in relation to the dry matter of the crude drug is calculated. ２０ H １８ ClNO ４ In the 18th edition of the Japanese Pharmacopoeia, Phellodendron amurensis Ruprecht or Phellodendron chinense Schneider (Rutaceae) bark without the periderm is described as containing 1.2% or more of berberine [berberine chloride (C)] relative to the dry matter of the crude drug. ２０ H １８ ClNO ４The 2021 Quasi-drug Ingredients Standards state that Phellodendron bark extract is an extract obtained by extracting the bark of Phellodendron amurensis Rupr. (Rutaceae) or other plants of the same genus, with the periderm removed, with water, ethanol, propylene glycol, 1,3-butylene glycol, or a mixture thereof.

[0014] The content of component (A) in the oral composition, in terms of berberine, is preferably 0.001% by mass or more, more preferably 0.0015% by mass or more, even more preferably 0.002% by mass or more, and preferably 0.005% by mass or less, more preferably 0.004% by mass or less, and even more preferably 0.003% by mass or less, relative to the total mass of the oral composition. When the content of component (A) is equal to or greater than the above-mentioned lower limit, the selective antibacterial effect against oral pathogenic bacteria and the stability of berberine during storage of the oral composition are improved. When the content of component (A) is equal to or less than the above-mentioned upper limit, the inhibition of the growth of bacteria other than pathogenic bacteria in the oral cavity by component (A) can be suppressed, thereby improving the selective antibacterial effect against pathogenic bacteria. Furthermore, the unpleasant taste (bitterness) during use of the oral composition is suppressed, resulting in a pleasant usability. The above-mentioned lower limit and upper limit can be combined as appropriate. For example, it may be 0.001 to 0.005% by mass, 0.0015 to 0.004% by mass, or 0.002 to 0.003% by mass. The amount of component (A) converted to berberine is determined in accordance with the provisions of various official compendia, such as the 18th Edition of the Japanese Pharmacopoeia.

[0015] When the (A) component is at least one selected from the group consisting of Phellodendron bark and Phellodendron bark extract, the content of the (A) component, calculated as the dry matter of the herb (Phiellodendron bark), is preferably 0.02% by mass or more, more preferably 0.03% by mass or more, even more preferably 0.04% by mass or more, and preferably 0.1% by mass or less, more preferably 0.08% by mass or less, and even more preferably 0.06% by mass or less, based on the total mass of the oral composition. When the content of the (A) component is equal to or greater than the above-mentioned lower limit, the selective antibacterial effect against oral pathogenic bacteria and the stability of berberine during storage of the oral composition are improved. When the content of the (A) component is equal to or less than the above-mentioned upper limit, the inhibition of the growth of bacteria other than pathogenic bacteria in the oral cavity by the (A) component can be suppressed, thereby improving the selective antibacterial effect against pathogenic bacteria. Furthermore, the unpleasant taste (bitterness) during use of the oral composition is suppressed, resulting in a pleasant usability. The above-mentioned lower limit and upper limit can be combined as appropriate. For example, it may be 0.02 to 0.1 mass %, may be 0.03 to 0.08 mass %, or may be 0.04 to 0.06 mass %.

[0016] <Component (B)> Component (B) is sodium tetradecene sulfonate. Component (B) has the effect of enhancing the selective antibacterial action of component (A) and the effect of increasing the duration of the selective antibacterial action. Furthermore, component (B) is highly effective in removing carious biofilms, and is also expected to have a caries prevention effect.

[0017] The content of component (B) in the oral composition is preferably 0.05% by mass or more, more preferably 0.08% by mass or more, even more preferably 0.1% by mass or more, and preferably 0.5% by mass or less, more preferably 0.3% by mass or less, and even more preferably 0.2% by mass or less, relative to the total mass of the oral composition. When the content of component (B) is equal to or greater than the above-mentioned lower limit, the selective antibacterial effect is easily enhanced and the duration of the effect is improved. When the content of component (B) is equal to or less than the above-mentioned upper limit, the inhibition of the growth of bacteria other than pathogenic bacteria in the oral cavity by component (B) can be suppressed, thereby improving the selective antibacterial effect against pathogenic bacteria. Furthermore, while component (B) has a distinctive bitter taste, when the content of component (B) is equal to or less than the above-mentioned upper limit, the bitter taste of component (B) is suppressed, resulting in a good usability. The above-mentioned lower limit and upper limit can be combined as appropriate. For example, it may be 0.05 to 0.5 mass %, may be 0.08 to 0.3 mass %, or may be 0.1 to 0.2 mass %.

[0018] In the oral composition, when the mass of component (A) in terms of berberine is A and the mass of component (B) is B, the ratio B / A is 20 or more, preferably 40 or more, and 200 or less, preferably 120 or less. When the ratio B / A is equal to or greater than the above-mentioned lower limit, the selective antibacterial effect against oral pathogenic bacteria is improved. When the ratio B / A is equal to or less than the above-mentioned upper limit, the inhibition of the growth of bacteria other than pathogenic bacteria in the oral cavity by component (B) can be suppressed, thereby improving the selective antibacterial effect against pathogenic bacteria. In addition, the stability of berberine in the oral composition is good. The above-mentioned lower limit and upper limit can be appropriately combined. For example, the ratio may be 20 to 200, or 40 to 120.

[0019] <Component (C)> Component (C) is a nonionic surfactant. According to the inventors' investigations, the presence of both components (A) and (B) tends to decrease the stability of berberine during storage of the oral composition. Furthermore, the inclusion of component (C) can increase the stability of berberine, allowing it to maintain its excellent selective antibacterial activity even after storage.

[0020] 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, polyglycerin 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, polyoxyethylene polyoxypropylene fatty acid esters, glycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyoxyethylene glycol fatty acid esters, polyoxyethylene phytosterols and phytostanols, polyoxyethylene lanolin and lanolin alcohols, polyoxyethylene alkylamines and fatty acid amides, polyoxyethylene alkylphenyl formaldehyde condensates, polyoxyethylene polyoxypropylene alkyl ethers, and polyoxyethylene alkylphenyl ethers. Among these, from the viewpoint of the stability of the oral composition during storage, at least one selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, sorbitan fatty acid ester, and polyglycerin fatty acid ester is preferred, and polyoxyethylene hydrogenated castor oil is more preferred.

[0021] The number of carbon atoms in the alkyl chain of the polyoxyethylene alkyl ether is, for example, 12 or more, preferably 14 or more, and for example, 26 or less, preferably 24 or less, more preferably 22 or less. Therefore, the number of carbon atoms in the alkyl chain is, for example, 12 to 26, preferably 14 to 24, more preferably 14 to 22. The alkyl chain may have an unsaturated bond. If the alkyl chain has an unsaturated bond, the number of unsaturated bonds must be at least one, preferably one. The alkyl chain may be either linear or branched, but linear chains are preferred. The average number of moles of ethylene oxide added in the polyoxyethylene alkyl ether is, for example, 5 or more, preferably 10 or more, and for example, 100 or less, preferably 60 or less. Therefore, the average number of moles of ethylene oxide added is, for example, 5 to 100, preferably 10 to 60. Examples of polyoxyethylene alkyl ethers include polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, and polyoxyethylene oleyl ether.

[0022] The average number of moles of ethylene oxide added in the polyoxyethylene hydrogenated castor oil is, for example, 3 or more, preferably 5 or more, and for example, 150 or less, preferably 100 or less. Therefore, the average number of moles of ethylene oxide added is, for example, 3 to 150, preferably 5 to 100. The number of carbon atoms in the fatty acid of the sorbitan fatty acid ester is, for example, 12 to 18. The number of carbon atoms in the fatty acid of the polyoxyethylene sorbitan fatty acid ester is, for example, 16 to 18, and the average number of moles of ethylene oxide added is, for example, 10 to 40. The number of carbon atoms in the alkyl chain of the alkylolamide is, for example, 12 to 14. The component (C) may be used alone or in combination of two or more.

[0023] The content of component (C) in the oral composition is preferably 0.5% by mass or more, more preferably 1% by mass or more, and preferably 2.5% by mass or less, more preferably 2% by mass or less, relative to the total mass of the oral composition. When the content of component (C) is equal to or greater than the above-mentioned lower limit, the effect of improving the stability of berberine is easily achieved. When the content of component (C) is equal to or less than the above-mentioned upper limit, liquid separation of the formulation can be suppressed. The above-mentioned lower limit and upper limit can be appropriately combined. For example, it may be 0.5 to 2.5% by mass, or 1 to 2% by mass.

[0024] In the oral composition, when the mass of component (A) in terms of berberine is A and the mass of component (C) is C, the ratio C / A is preferably 100 or more, more preferably 200 or more, and preferably 2500 or less, more preferably 2000 or less. When the ratio C / A is equal to or greater than the above-mentioned lower limit, the stability of berberine is excellent. When the ratio C / A is equal to or less than the above-mentioned upper limit, liquid separation of the preparation can be suppressed. The above-mentioned lower limit and upper limit can be appropriately combined. For example, it may be 100 to 2500 or 200 to 2000.

[0025] In the oral composition, when the mass of component (B) is B and the mass of component (C) is C, the ratio C / B is preferably 1 or more, more preferably 2 or more, and preferably 50 or less, more preferably 40 or less. When the ratio C / B is equal to or greater than the above-mentioned lower limit, the stability of berberine is excellent. When the ratio C / B is equal to or less than the above-mentioned upper limit, liquid separation of the preparation can be suppressed. The above-mentioned lower limit and upper limit can be combined as appropriate. For example, it may be 1 to 50, or 2 to 40.

[0026] In the oral composition, it is preferred that the ratio represented by C / A is 100 to 2500 and the ratio represented by C / B is 1 to 50, and it is more preferred that the ratio represented by C / A is 100 to 2500 and the ratio represented by C / B is 1 to 50.

[0027] Other Components The other components may be any component other than component (A), component (B), and component (C), such as bactericides, preservatives, medicinal ingredients, surfactants, abrasives, humectants, binders, buffers, solubilizers, isotonicity agents, stabilizers, chelating agents, moisturizers, flavoring agents (sweeteners, flavorings, acidulants), oily components, colorants, pH adjusters, solvents, excipients, disintegrants, binders, lubricants, colorants, antioxidants, strengthening agents, leavening agents, thickeners, cooling agents, astringents, UV absorbers, aqueous solvents, seasonings, and food ingredients (including food additives). These components may be used alone or in combination of two or more. The type and content of the other components may be selected depending on the intended use and / or dosage form, method of use, etc. of the oral composition.

[0028] - Disinfectant - Examples of disinfectants include cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, sodium lauroyl sarcosinate, alkyldiaminoethylglycine hydrochloride, chlorhexidine or a salt thereof, triclosan, isopropylmethylphenol, hinokitiol, chlorhexidine gluconate, dequalinium chloride, iodine, potassium iodide, sulfamethoxazole, sulfamethoxazole sodium, sulfisoxazole, and sulfisomidine sodium.

[0029] The above-mentioned bactericide exhibits antibacterial activity not only against pathogenic bacteria in the oral cavity but also against resident bacteria. Therefore, from the viewpoint of improving the oral flora, it is preferable that the oral composition does not contain a bactericide (the bactericide content is 0%). However, a bactericide may be contained within a range that does not impair the effects of the present invention. The content of the bactericide in the oral composition is preferably 0.3% by mass or less, more preferably 0.1% by mass or less, even more preferably 0.05% by mass or less, particularly preferably 0.01% by mass or less, and most preferably 0.005% by mass or less, relative to the total mass of the oral composition. When the bactericide content is equal to or less than the above-mentioned upper limit, non-selective antibacterial activity against pathogenic bacteria and resident bacteria is suppressed, thereby reducing the risk of microbial replacement due to a disruption of the balance of bacteria constituting the oral flora.

[0030] - Preservatives - Examples of preservatives include paraoxybenzoic acid esters such as methylparaben, ethylparaben, propylparaben, and butylparaben, benzoic acid or a salt thereof, dehydroacetic acid or a salt thereof, propionic acid or a salt thereof, sorbic acid or a salt thereof (potassium sorbate, etc.), boric acid, borax, phenylethyl alcohol, benzyl alcohol, phenol, alcohol derivatives such as acrinol, and alkylpolyaminoethylglycine.

[0031] The preservative exhibits antibacterial activity not only against pathogenic bacteria in the oral cavity but also against resident bacteria. Therefore, from the perspective of improving the oral flora, it is preferable that the oral composition does not contain a preservative (preservative content is 0%). However, a preservative may be contained within a range that does not impair the effects of the present invention. The content of the preservative in the oral composition is preferably 0.3% by mass or less, more preferably 0.1% by mass or less, even more preferably 0.05% by mass or less, particularly preferably 0.01% by mass or less, and most preferably 0.005% by mass or less, based on the total mass of the oral composition. When the preservative content is equal to or less than the above upper limit, non-selective antibacterial activity against pathogenic bacteria and resident bacteria is suppressed, thereby reducing the risk of microbial replacement due to a disruption of the balance of bacteria constituting the oral flora.

[0032] The total content of the bactericide and preservative in the oral composition is preferably 0.5% by mass or less, more preferably 0.3% by mass or less, even more preferably 0.1% by mass or less, particularly preferably 0.01% by mass or less, and most preferably 0.005% by mass or less, relative to the total mass of the oral composition. When the total content of the bactericide and preservative is equal to or less than the upper limit, non-selective antibacterial activity against pathogenic bacteria and resident bacteria can be suppressed, and the risk of bacterial replacement due to a disruption in the balance of bacteria constituting the oral flora can be reduced.

[0033] -Medicinal Ingredients- Examples of medicinal ingredients include enzymes such as dextranase, mutanase, amylase, protease, and Liteque enzyme; fluorides such as sodium fluoride, sodium monofluorophosphate, and stannous fluoride; anti-inflammatory agents such as tranexamic acid, epsilon aminocaproic acid, allantoin, glycyrrhizinates (e.g., dipotassium glycyrrhizinate), allantoin chlorohydroxyaluminum, azulene, and dihydrocholesterol; metal salts such as zinc salts, copper salts, and tin salts; anti-tartar agents such as condensed phosphates and ethanehydroxydiphosphonate; and vitamin E (e.g., tocopherol acetate). Examples of the active ingredient include blood flow promoters, dentin hypersensitivity inhibitors such as strontium chloride, coating agents such as hydroxyethyl cellulose dimethyl diallyl ammonium chloride, astringents such as vitamin C (e.g., ascorbic acid or a salt thereof), lysozyme chloride, sodium chloride, water-soluble copper compounds such as copper chlorophyll, amino acids such as alanine, glycine, proline, potassium L-aspartate, magnesium L-aspartate, aminoethylsulfonic acid, sodium chondroitin sulfate, plant extracts such as thyme, Scutellaria Root, clove, and witch hazel, callopeptides, polyvinylpyrrolidone, etc. Other examples include decongestants, anti-inflammatory agents, antihistamines, vitamins, local anesthetics, ingredients having a bacterial flora-improving effect other than the active ingredient of the present invention, and combinations of two or more selected from these. Decongestants include, for example, naphazoline hydrochloride, tetrahydrozoline hydrochloride, phenylephrine hydrochloride, epinephrine, epinephrine hydrochloride, ephedrine hydrochloride, dl-methylephedrine hydrochloride, tetrahydrozoline nitrate, and naphazoline nitrate. Anti-inflammatory agents include, for example, neostigmine methylsulfate, allantoin, zinc sulfate, zinc lactate, lysozyme chloride, bromelain, dipotassium glycyrrhizinate, ammonium glycyrrhizinate, glycyrrhetinic acid, methyl salicylate, sodium azulene sulfonate, chamomile, and sodium cromoglycate. Antihistamines include, for example, iproheptine hydrochloride, diphenhydramine hydrochloride, diphenhydramine, isothipendyl hydrochloride, and chlorpheniramine maleate.Examples of vitamins include flavin adenine dinucleotide sodium, pyridoxine hydrochloride, cyanocobalamin, vitamin A's (e.g., retinol acetate, retinol palmitate), and vitamin E's (tocopherol acetate (e.g., d-α-tocopherol acetate)). Examples of local anesthetics include lidocaine, lidocaine hydrochloride, dibucaine hydrochloride, and chlorobutanol. These medicinal ingredients may be used alone or in combination of two or more. The content of the medicinal ingredient can be appropriately determined as an effective amount according to conventional methods.

[0034] Surfactant—As the surfactant, surfactants other than component (B) and component (C) can be contained to the extent that the effects of the present invention are not impaired. Examples include anionic surfactants other than component (B) and amphoteric surfactants. Examples of anionic surfactants include alkyl sulfates, acylamino acid salts, acyltaurine salts, hydrogenated coconut fatty acid monoglyceride monosulfate, and lauryl sulfoacetate. Salts of these anionic surfactants 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. The alkyl group in the alkyl sulfate, and the acyl group in the acylamino acid salt or acyltaurine salt may each be either linear or branched, and may be either saturated or unsaturated. The number of carbon atoms is, for example, 10 to 20, preferably 12 to 18, and more preferably 12 to 14. Examples of alkyl sulfates include 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 salt and cocoyl glycine salt; acylalanine salts such as N-lauroyl-β-alanine salt, N-myristoyl-β-alanine salt, N-cocoyl-N-methyl-β-alanine salt, and N-methyl-N-acylalanine salt; and acylaaspartates such as lauroyl aspartate. Examples of acyltaurine salts include N-methyl-N-acyltaurine salts and N-cocoylmethyl taurine salts. Examples of anionic surfactants include hydrogenated coconut fatty acid monoglyceride sodium monosulfate and sodium lauryl sulfoacetate.Examples of amphoteric surfactants include betaine-type amphoteric surfactants such as alkyldimethylaminoacetic acid betaines (e.g., lauryldimethylaminoacetic acid betaine) and fatty acid amidopropyldimethylaminoacetic acid betaine; imidazoline-type amphoteric surfactants such as N-fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine salts and coconut oil fatty acid imidazolinium betaine; and alkyl betaines such as lauryldimethylaminoacetic acid betaine. When the oral composition contains a surfactant other than component (B) and component (C), the content thereof is, for example, 0.01 to 10% by mass, preferably 0.1 to 5% by mass, and more preferably 0.2 to 3% by mass, relative to the total mass of the oral composition.

[0035] -Abrasives- Examples of abrasives include inorganic abrasives and organic abrasives. Examples of inorganic abrasives include abrasive silica such as precipitated silica, silica gel, aluminosilicate, zirconosilicate, crystalline zirconium silicate, and titanium-bonded silica; silicate-based materials such as zeolite and zirconium silicate; calcium phosphate-based compounds such as dibasic calcium phosphate dihydrate or anhydrate, monobasic calcium phosphate, tribasic calcium phosphate, and calcium pyrophosphate; calcium carbonate-based compounds such as calcium carbonate; calcium-based compounds other than carbonate / phosphate such as calcium hydroxide and calcium sulfate; aluminum-based materials such as aluminum oxide, aluminum hydroxide, and alumina; magnesium-based materials such as magnesium carbonate and tribasic magnesium phosphate; apatite-based materials such as hydroxyapatite, fluoroapatite, and calcium-deficient apatite; titanium-based materials such as titanium dioxide, titanium mica, and titanium oxide; and minerals such as bentonite. Examples of inorganic abrasives include granulated particles formed by forming water-insoluble powder into granules. Examples of water-insoluble powders include the above-mentioned silica, silicic acid materials, calcium phosphate compounds, calcium carbonate compounds, calcium compounds other than carbonate / phosphate, magnesium materials, apatite materials, minerals, and mixtures thereof. Furthermore, water-soluble compounds such as sodium silicate and cellulose derivatives can be used as binders for these granulated particles. Examples of organic abrasives include synthetic resin-based abrasives such as polymethyl methacrylate. Of these, abrasive silica, silicic acid materials, and calcium carbonate compounds are preferred, with abrasive silica being more preferred. The content of the abrasive is preferably 50% by mass or less, more preferably 8 to 50% by mass, based on the total mass of the oral composition.

[0036] Humectants: Examples of humectants include sugar alcohols and polyhydric alcohols other than sugar alcohols. Examples of sugar alcohols include 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, for example, 70% by weight or less, preferably 5 to 65% by weight, and more preferably 20 to 60% by weight, relative to the total weight of the oral composition.

[0037] - Binder - By including a binder in the composition, the viscosity of the composition can be optimized, and shape retention and usability can be further improved. Examples of binders include organic binders and inorganic binders. Examples of organic binders include polysaccharides, cellulose-based binders (e.g., carboxymethyl cellulose (CMC) or its salts (e.g., sodium salts), 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). Examples of inorganic binders include thickening silica and aluminum silicate. These binders may be used alone or in combination of two or more. The binder content is, for example, 10% by mass or less relative to the total mass of the oral composition. The organic binder content is preferably 0 to 3% by mass, more preferably 0.1 to 2% by mass, relative to the total mass of the oral composition. The inorganic binder content is preferably 0 to 10% by mass, more preferably 1 to 8% by mass, relative to the total mass of the oral composition.

[0038] -Buffering Agent- Examples of buffering agents include citric acid or a salt thereof (e.g., sodium citrate), phosphoric acid or a salt thereof (e.g., sodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate), tartaric acid or a salt thereof (e.g., sodium tartrate), gluconic acid or a salt thereof (e.g., sodium gluconate), acetic acid or a salt thereof (e.g., sodium acetate), carbonic acid or a salt thereof (e.g., sodium bicarbonate), trometamol, amino acids (e.g., potassium aspartate, aminoethylsulfonic acid, glutamic acid, sodium glutamate), and combinations of two or more thereof.

[0039] -Solubilizing Agent- Examples of solubilizing agents include propylene glycol, polyethylene glycol, and combinations of two or more thereof.

[0040] -Isotonicity Agent- Examples of isotonicity agents include sodium chloride, potassium chloride, glycerin, and combinations of two or more of these.

[0041] -Stabilizer- Examples of stabilizers include sodium edetate, cyclodextrin, sulfite, citric acid or a salt thereof, dibutylhydroxytoluene, ascorbic acid, sodium sulfate, and combinations of two or more thereof.

[0042] Chelating Agents Examples of chelating agents include sodium edetate, sodium citrate, and combinations thereof.

[0043] - Moisturizing Agents - Examples of moisturizing agents include glycerin, concentrated glycerin, sugar alcohols (for example, sorbitol, xylitol, maltitol, mannitol, reduced starch syrup, reduced palatinose, erythritol, lactitol, and isomalt), and combinations of two or more of these.

[0044] Flavoring agents include, for example, sweeteners (e.g., saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia, stevioside, paramethoxycinnamic aldehyde, neohesperidin dihydrochalcone, perillartine, aspartyl phenylalanine methyl ester, thaumatin, acesulfame potassium, sucralose, maltitol, sorbitol, mannitol, reduced starch syrup, reduced palatinose, xylitol, erythritol, lactitol, and other artificial sweeteners); flavorings. (e.g., natural essential oils such as anise oil, cassia oil, wintergreen oil, mastic oil, neroli oil (orange flower oil), lemongrass oil, jasmine oil, rose oil, iris oil, clove oil, sage oil, cardamom oil, rosemary oil, laurel oil, chamomile oil, basil oil, marjoram oil, lemon oil, orange oil, lime oil, yuzu oil, nutmeg oil, lavender oil, paracles oil, vanilla oil, cinnamon oil, pimento oil, cinnamon leaf oil, perilla oil, wintergreen oil, peppermint oil, and lychee oil); menthol, carvone, cinnamic acid Fragrance components contained in the above natural essential oils, such as aldehyde, anethole, methyl salicylate, eugenol, linalool, limonene, menthone, menthyl acetate, citral, decanal, camphor, borneol, pinene, spilanthol, n-decyl alcohol, citronellol, α-terpineol, citronellyl acetate, ethyl linalool, and vanillin; ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl fragrance components such as ethylphenyl glycidate, benzaldehyde, vanillin, ethyl vanillin, furaneol, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, and ethylene glycol-1-menthyl carbonate; and various blended flavors such as mint, fruit, and herb flavors that are obtained by combining several fragrance components and natural essential oils (e.g., Peppermint Micron X-8277-T, Dry Coat Matcha #421), acidulants (e.g., citric acid, tartaric acid, malic acid), and green tea powder.

[0045] -Oil-Based Component- Examples of oil-based components include fatty acid esters (e.g., glycerin fatty acid esters), hydrocarbons (e.g., paraffin, liquid paraffin, ceresin, squalane, petrolatum, microcrystalline wax), higher fatty acids (e.g., fatty acids having 8 to 22 carbon atoms, such as lauric acid, myristic acid, oleic acid, and isostearic acid), higher alcohols (e.g., alcohols having 8 to 22 carbon atoms, such as lauryl alcohol, cetyl alcohol, cetostearyl alcohol, oleyl alcohol, and isostearyl alcohol), vegetable oils and fats (e.g., vegetable oils such as olive oil, castor oil, and coconut oil; fatty acid esters such as isopropyl myristate), beeswax, and combinations of two or more thereof.

[0046] Colorants Examples of colorants include natural dyes such as safflower red pigment, gardenia yellow pigment, gardenia blue pigment, perilla pigment, monascus koji pigment, red cabbage pigment, carrot pigment, hibiscus pigment, cacao 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 chlorophyllin, and titanium dioxide. When the oral composition contains a colorant, the content thereof is preferably 0.00001 to 3% by mass relative to the total mass of the oral composition.

[0047] 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 (e.g., potassium salt, sodium salt, and ammonium salt), inorganic acids such as phosphoric acid (orthophosphoric acid) or their salts (e.g., potassium salt, sodium salt, and ammonium salt), and hydroxides such as sodium hydroxide and potassium hydroxide. Examples of organic acid salts include sodium citrate. Examples of inorganic acid salts include disodium hydrogen phosphate and sodium dihydrogen phosphate. The content of the pH adjuster can be, for example, an amount that results in a pH of 5 to 9, preferably 6 to 8.5, of the oral composition after addition of the pH adjuster. In this specification, the pH value generally refers to the value measured 3 minutes after the start of measurement at 25°C. The pH value can be measured, for example, using a pH meter (model number Hm-30S) manufactured by Toa Denpa Kogyo Co., Ltd.

[0048] -Solvent- Examples of the solvent include water (purified water, sterilized water, etc.) and ethanol, with water being preferred. The solvent may be used alone or in combination of two or more.

[0049] -Excipients- Examples of excipients include celluloses such as hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, crystalline cellulose, ethyl cellulose, methylethyl cellulose, and low-substituted hydroxypropyl cellulose, and pharmacologically acceptable derivatives thereof; synthetic polymers such as polyvinylpyrrolidone and partially saponified polyvinyl alcohol; polysaccharides such as gelatin, powdered gum arabic, pullulan, agar, alginic acid, sodium alginate, and xanthan gum; corn starch, potato starch, pregelatinized starch, and hydroxypropyl starch. starch such as lactic acid, and pharmacologically acceptable derivatives thereof; lactose, lactose granules, fructose, glucose, sucrose, granulated sugar, hydrous glucose, trehalose, palatinose, mannitol, sorbitol, erythritol, xylitol, maltotetraose, lactitol, isomalt, reduced palatinose, reduced starch syrup, powdered reduced maltose starch syrup, maltitol; inorganic excipients such as magnesium carbonate, calcium carbonate, light anhydrous silicic acid, silicon dioxide (also known as anhydrous silicic acid, fine silicon dioxide), titanium oxide, aluminum hydroxide gel, and combinations of two or more thereof.

[0050] Disintegrants include, for example, crospovidone, carmellose calcium, carmellose sodium, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose (CMC) or a salt thereof (for example, a sodium salt), carboxymethyl starch sodium, croscarmellose sodium, cross-linked insoluble polyvinylpyrrolidone, hydroxypropyl starch, partially pregelatinized starch, corn starch, and combinations of two or more thereof.

[0051] - Binder - Examples of binders include hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, ethyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, gelatin, dextrin, starch, pregelatinized starch, and combinations of two or more thereof.

[0052] - Lubricant - Examples of lubricants include calcium stearate, magnesium stearate, sucrose fatty acid esters, light anhydrous silicic acid, sodium stearyl fumarate, polyethylene glycol, talc, stearic acid, and combinations of two or more thereof.

[0053] Examples of optional components other than those mentioned above include polyisobutylene, polybutadiene, urethane, silicone, and natural rubber. The content of these components can be appropriately set within a range that does not impair the effects of the present invention.

[0054] <Form, Dosage Form> The oral composition can be prepared in various forms, such as liquid, paste, or solid, and the dosage form is not particularly limited. In the present invention, the oral composition refers to a composition intended primarily for use in the oral cavity. The oral composition may be an oral preparation that is excreted from the oral cavity after use, or may be an ingestible food or beverage. Examples of oral preparations include dentifrices (liquid dentifrice, liquid dentifrice, toothpaste, lubricant dentifrice, powder dentifrice, etc.), mouthwashes, mouthwashes, liniments, mouth sprays, patches, sheets, oral sustained-release preparations, chewable preparations, oral dissolving preparations, oral disintegrating preparations, tongue care preparations, mouth fresheners, denture care preparations, etc. Examples of food or beverage products include chewing gum, tablets, candies, gummies, edible films, and lozenges that are placed in the oral cavity; and powdered beverages that are dissolved in water and consumed. As the food and drink, any one of chewing gum, tablet confectionery, candy, gummy candy, and edible film is preferable from the viewpoint of convenience and portability that allows use anytime and anywhere.

[0055] <Manufacturing Method> The method for manufacturing the oral composition is not particularly limited, and the composition can be prepared by a conventional method depending on the form and dosage form of the oral composition. For example, when used as a toothpaste, a method can be used in which solvent-soluble components are dissolved in a solvent, and other insoluble components are mixed, followed by degassing (e.g., under reduced pressure) as needed. Another example can be a method in which the active ingredient and other components used as needed are dispersed and dissolved in a solvent (e.g., purified water, sterilized water, etc.). The resulting oral composition can be placed in a container to produce a finished product. The shape and material of the container are not particularly limited, and containers commonly used for oral compositions can be used. For example, a laminated tube can be used as a toothpaste container. Examples of materials for the laminated tube include plastics such as polyethylene, polypropylene, polyethylene terephthalate, and nylon.

[0056] <Uses> The oral composition of this embodiment has excellent selective antibacterial activity against pathogenic bacteria in the oral cavity, and is therefore preferably used to improve the oral flora. In the present invention, improving the oral flora means reducing the ratio of the number of pathogenic bacteria to the total number of oral bacteria. A selective antibacterial activity means that the antibacterial activity is active only against a specific bacterial species among multiple bacteria, and that the antibacterial activity is inactive against other bacteria, or that the antibacterial activity is weaker than that against the specific bacterial species. In other words, the oral composition of this embodiment can reduce the ratio of pathogenic bacteria (one or more species) to the total number of oral bacteria and increase the ratio of resident bacteria (one or more species), thereby reducing the risk of diseases such as periodontal disease.

[0057] Among oral bacteria, pathogenic bacteria include Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum, which cause periodontal disease and bad breath, and Streptococcus mutans, which causes dental caries. The oral composition of this embodiment has an excellent selective antibacterial effect against Porphyromonas gingivalis, among the above bacteria, and can reduce the ratio of the number of Porphyromonas gingivalis bacteria to the total number of oral bacteria, thereby reducing the risk of periodontal disease and bad breath. Therefore, the oral composition of this embodiment is particularly preferably used to reduce the ratio of the number of Porphyromonas gingivalis bacteria to the total number of oral bacteria.

[0058] The oral composition of this embodiment can be used in any manner as long as it is present in the oral cavity. Presence of the oral composition in the oral cavity exerts a selective antibacterial effect against pathogenic bacteria in the oral cavity, thereby improving the oral flora. When the oral composition of this embodiment is an oral preparation, its usage may be similar to that of a typical oral preparation, including, for example, placing an appropriate amount of the composition on a toothbrush, brushing the tooth surface, and rinsing with water after use (dentifrice), holding an appropriate amount of the composition in the mouth, gargling, and then spitting it out (mouthwash), chewing and swallowing an appropriate amount of the composition (oral tablet), or spraying an appropriate amount into the oral cavity (oral spray). When the oral composition of this embodiment is a food or beverage, it may be consumed in the same manner as a typical food or beverage. The amount of the oral composition applied to the oral cavity per dose may be similar to the typical amount depending on the dosage form, for example, approximately 0.5 to 1.5 g in the case of a dentifrice. The number of times the oral composition is applied to the oral cavity per day can be appropriately determined so as to obtain the desired selective antibacterial effect, and is not particularly limited, and may be, for example, 1 to 2 times or more.

[0059] The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following descriptions. "%" indicates "% by mass" unless otherwise specified.

[0060] (Ingredients Used) <Component (A)> Phellodendron Bark Extract: Manufactured by Ogi Pharmaceutical Co., Ltd., Trade Name: Phellodendron Bark Extract S, Berberine Content 5%. Berberine Chloride: Manufactured by Alps Pharmaceutical Co., Ltd., Trade Name: Berberine Chloride Hydrate. <Component (B)> Sodium Tetradecene Sulfonate: Manufactured by Lion Specialty Chemicals Co., Ltd., Trade Name: K-Lipolan PJ-400CJ. <Component (C)> Polyoxyethylene (5) Hydrogenated Castor Oil: Manufactured by Nippon Emulsion Co., Ltd., Trade Name: EMALEX HC-5. The numbers in parentheses indicate the average number of moles of ethylene oxide added.

[0061] (Test Example 1) <Preparation of Test Agent> Test agents (mouthwashes) of Example 1 and Comparative Example 1 were prepared by mixing the ingredients according to the compositions shown in Table 1. Purified water was also used as a control test agent. In Table 1, the berberine-equivalent amount of component (A) is the pure amount of berberine obtained by excluding impurities from component (A). The "balance" of purified water indicates the amount that makes the total amount of the test agent 100%.

[0062]

[0063] The selective antibacterial activity of each test agent was evaluated by the following method, and the results are shown in Table 2.

[0064] <Evaluation of Selective Antibacterial Activity> [Bacteria Used] The following bacterial species purchased from the American Type Culture Collection (hereinafter abbreviated as ATCC) were used as periodontal pathogens for evaluation. Periodontal pathogen: Porphyromonas gingivalis (P. gingivalis) ATCC 33277

[0065] [Bacterial Preculture] The above-mentioned frozen bacterial solution was inoculated into a blood plate medium of the following composition using a platinum loop and cultured anaerobically at 37°C for 72 hours (80% by volume nitrogen, 10% by volume carbon dioxide, 10% by volume hydrogen). Subsequently, colonies grown on the blood plate medium were suspended in 4 mL of a medium (hereinafter also referred to as THBHM) prepared by adding hemin (Sigma-Aldrich) and vitamin K (Fujifilm Wako Pure Chemical Industries, Ltd.) to final concentrations of 5 mg / L and 1 mg / L, respectively, and cultured anaerobically at 37°C for 24 hours. Furthermore, this culture was inoculated into 20 mL of THBHM at 1% and cultured anaerobically at 37°C for 24 hours.

[0066] Composition of blood plate medium: Todd-Heavitt broth (Becton, Dickinson) 30 g / L, agar (Becton, Dickinson) 15 g / L, hemin (Sigma-Aldrich) 5 mg / L, vitamin K (Fujifilm Wako Pure Chemical Industries, Ltd.) 1 mg / L, distilled water, balance: defibrinated horse blood (Japan Biomaterials Center) 50 mL. The blood plate medium was prepared by mixing Todd-Heavitt broth, agar, hemin, vitamin K, and a small amount of water, adding water to the resulting mixture so that the total volume was 1 L, autoclaving at 121°C for 20 minutes, and then adding defibrinated horse blood.

[0067] [Evaluation of in vitro selective antibacterial activity using human saliva] The selective antibacterial activity of each test agent was evaluated according to the method described in Journal of Oral Biosciences, 2023, Vol. 65, No. 1, pp. 72-79. Specifically, the selective antibacterial activity was evaluated by the following procedure. (i) P. gingivalis, a periodontal pathogen, (ii) human saliva, and (iii) test agent were each added to a final concentration of (i) 2.5 × 10 ７Sample solutions were prepared by adding the test agent to BM medium of the following composition to achieve (i) CFU / mL, (ii) 2% (v / v), and (iii) evaluation concentrations. The evaluation concentrations were undiluted, 3-fold diluted, 15-fold diluted, 30-fold diluted, or 60-fold diluted. For the "undiluted" sample, the test agent was added without dilution so that the berberine-equivalent concentration of component (A) in the sample solution was 25 ppm. For the control without component (A), the same amount was added as in the "undiluted" sample in Example 1 and Comparative Example 1. For the "n-fold diluted" sample (n = 3, 15, 30, or 60), the test agent was diluted n-fold with purified water, and the diluted test agent was added in the same amount as in the "undiluted" sample. Because the control contained no components other than purified water, the results for the "undiluted" sample were considered to be the results for the "n-fold diluted" sample. The prepared sample solutions were cultured under anaerobic conditions for 24 hours. After incubation, bacteria in the sample solution were collected by centrifugation, and DNA was extracted. This was amplified by PCR (polymerase chain reaction) using primers designed to cover the variable region, V1-V2, of the 16S rRNA gene, and then sequenced. A quality check was performed on the obtained sequence, and 3,000 sequence data reads that passed this were used for analysis. Operational taxonomic units (OTUs) clustering was performed using the UCLUST algorithm with a threshold of 97% homology. Furthermore, bacterial species were identified by comparing with existing databases, and the ratio (%) of P. gingivalis bacterial reads to the total bacterial reads (hereinafter also referred to as the P. gingivalis ratio) was calculated. The selective antibacterial effect against periodontal pathogens was evaluated from the P. gingivalis ratio in the case of a 60-fold dilution using the following evaluation criteria. Evaluation criteria (at 60-fold dilution): ◎: P. ◯: The ratio of P. gingivalis is 5% or more and less than 10%. ×: The ratio of P. gingivalis is 10% or more.

[0068] Composition of BM medium: Proteose peptone (Becton, Dickinson) 5 g / L, tryptone (Becton, Dickinson) 2.5 g / L, yeast extract (Becton, Dickinson) 2.5 g / L, KCl (Fujifilm Wako Pure Chemical Industries, Ltd.) 1.25 g / L, cysteine ​​(Fujifilm Wako Pure Chemical Industries, Ltd.) 0.25 g / L, phosphate buffer (Fujifilm Wako Pure Chemical Industries, Ltd.) 0.02 mol / L, hemin (Sigma-Aldrich) 5 mg / L, vitamin K (Fujifilm Wako Pure Chemical Industries, Ltd.) 1 mg / L

[0069]

[0070] As shown in the above results, the selective antibacterial activity of the test agent of Comparative Example 1, which does not contain component (B), significantly decreased when the dilution ratio was 15 times or more, reaching a value close to that of the control. In contrast, the test agent of Example 1 exhibited excellent selective antibacterial activity against periodontal pathogens even when diluted 60 times. From these results, it is believed that the test agent of Example 1 exhibits excellent selective antibacterial activity not only immediately after application to the oral cavity, but also when the concentration in the oral cavity is reduced by rinsing, gargling, etc.

[0071] Test Example 2 Test agents (mouthwashes) of Example 2 and Comparative Example 2 were prepared by mixing the ingredients according to the compositions shown in Table 3. Purified water was used as a control test agent. In Table 3, the "balance" of purified water indicates the amount of purified water that makes the total amount of the test agent 100%.

[0072]

[0073] The selective antibacterial activity of each test agent was evaluated in the same manner as in Test Example 1. The results are shown in Table 4.

[0074]

[0075] As shown in the above results, even when berberine chloride was used instead of Phellodendron Bark extract as component (A), the same results as in Test Example 1 were obtained.

[0076] Test Example 3 Preparation of Dentifrice Compositions Gel-type dentifrice compositions (Examples 3-22, Comparative Examples 3-4) were prepared according to the formulations shown in Tables 5-7 using the following procedure. The prepared dentifrice compositions were filled into tube containers. First, component (A) and other water-soluble components were mixed and dissolved in purified water at room temperature (Mixture X). Next, an organic binder was dispersed in propylene glycol at room temperature (Mixture Y). Mixture Y and the inorganic binder were added to Mixture X while stirring to prepare Mixture Z. Next, components (B), (C), and a flavor were mixed into Mixture Z using a kneader at room temperature, and the mixture was degassed under reduced pressure (5.3 kPa) to obtain a dentifrice composition. However, in Comparative Example 3, neither component (B) nor component (C) was added, and in Comparative Example 4, component (B) was not added. In Tables 5-7, the numerical values ​​indicating the amount of component (A) represent the pure amount of berberine excluding impurities. The "balance" of purified water indicates the amount that brings the total amount of the dentifrice composition to 100%.

[0077] The selective antibacterial activity of the prepared dentifrice compositions was evaluated in the same manner as in Test Example 1. The stability and taste of berberine were also evaluated by the following methods. The results are shown in Tables 5 to 7.

[0078] <Evaluation of Berberine Stability> The berberine content of the dentifrice composition was measured immediately after preparation (initial) and after 6 months of storage at 40°C using the following method. 1 g of the dentifrice composition was removed from the tube at the end of the tube. An internal standard solution (a methanol solution of Quinoline Yellow SS (Fujifilm Wako Pure Chemical Industries)) and mobile phase were added to the removed dentifrice composition, and after uniform dispersion, the mixture was filtered using a liquid chromatography filter (0.45 μm) to obtain a sample solution. If necessary, the mixture was centrifuged after uniform dispersion. Separately, standard berberine chloride was dissolved in methanol and diluted with the mobile phase to match the berberine concentration of the dentifrice composition. The internal standard solution was then accurately added to obtain a standard solution. Liquid chromatography was performed on 20 μL of the sample solution and 20 μL of the standard solution under the following conditions. Operating conditions: Detector: ultraviolet absorption photometer (measurement wavelength: 345 nm) Column: ODS column Column temperature: room temperature Mobile phase: water / acetonitrile / methanol = 2 / 2 / 1 (appropriate amounts of sodium lauryl sulfate and tartaric acid added) Flow rate: adjusted so that the retention time of berberine is approximately 20 minutes

[0079] From the results of liquid chromatography, the ratio QT of the peak area of ​​berberine in the sample solution to that of the internal standard and the ratio QS of the peak area of ​​berberine in the standard solution to that of the internal standard were determined, and the berberine content was calculated using the following formula: Berberine content (ppm) = WS x (100 - D) x (353.37 / 371.81) x (QT / QS) x (K / WT) WS: Amount of standard berberine chloride (g) WT: Amount of sample (g) D: Water content of standard berberine chloride (%) K: Constant (set based on dilution concentration, etc.) 353.37: Molecular weight of berberine 371.81: Molecular weight of berberine chloride Internal standard: Quinoline Yellow SS

[0080] The residual berberine rate was calculated from the initial berberine content and the berberine content after 6 months of storage at 40°C using the following formula: berberine residual rate (%) = [(berberine content after 6 months of storage at 40°C) / (initial berberine content)] x 100

[0081] The berberine stability was evaluated based on the residual berberine rate according to the following criteria: Evaluation criteria: ◎: berberine residual rate is 95% or more ○: berberine residual rate is 90% or more but less than 95% △: berberine residual rate is 85% or more but less than 90% ×: berberine residual rate is less than 85%

[0082] <Evaluation of Taste> The taste of the dentifrice compositions was evaluated in a sensory test by 10 expert panelists. 1 g of the dentifrice composition was squeezed out of the tube container and placed on a toothbrush (Lion Corporation, Clinica Toothbrush 4-row head, medium), and brushed for 3 minutes. The taste (absence of bitterness) felt during use was judged using the following rating scale. The average of the ratings from the 10 panelists was calculated, and the taste (goodness of taste) was evaluated using the following rating scale. Rating scale: 4 points: No bitterness felt 3 points: Slight bitterness felt, but at a level that is not problematic in use 2 points: Bitterness felt, at a level that is problematic in use 1 point: Strong bitterness felt Rating scale: ◎: Average score of 3.5 points or more ○: Average score of 3 points or more but less than 3.5 points △: Average score of 2 points or more but less than 3 points ×: Average score less than 2 points

[0083]

[0084]

[0085]

[0086] The dentifrice compositions of Examples 3 to 22 were excellent in selective antibacterial activity. They also had good berberine stability and good taste. On the other hand, the dentifrice composition of Comparative Example 3, which did not contain component (B), was inferior in selective antibacterial activity. The dentifrice composition of Comparative Example 4, which had a B / A ratio of more than 200, was inferior in all of selective antibacterial activity, berberine stability, and taste.

[0087] Formulation Example 1 A toothpaste composition having the following composition was prepared according to the following procedure: (A) Phellodendron Bark Extract (berberine content 5%) 0.06% (B) Sodium tetradecene sulfonate 0.3% (C) Polyoxyethylene (5) hydrogenated castor oil 2.0% Liquid sorbitol (70%) 45% Abrasive silica 10% Thickening silica 3.0% Titanium oxide 0.4% Propylene glycol 4.0% Xanthan gum 1.2% Sodium polyacrylate 0.4% Sodium fluoride 0.32% Sodium lauryl sulfate 1.0% Coconut oil fatty acid amidopropyl betaine solution 1.0% Sodium saccharin 0.1% Flavoring 1.2% Purified water Balance Total 100%

[0088] <Method of Preparing Toothpaste Composition> First, component (A) and other water-soluble components were mixed and dissolved in purified water at room temperature (mixture X). Next, an organic binder was dispersed in propylene glycol at room temperature (mixture Y). Mixture Y and the inorganic binder were added to and mixed with mixture X while stirring to prepare mixture Z. Next, components (B) and (C), other surfactants, abrasives, and flavorings were mixed into mixture Z using a kneader at room temperature, and the mixture was defoamed under reduced pressure (5.3 kPa), yielding a toothpaste composition.

[0089] Formulation Example 2 A toothpaste composition having the following composition was prepared in the same manner as in Formulation Example 1. (A) Phellodendron Bark Extract (berberine content 5%) 0.05% (B) Sodium tetradecene sulfonate 0.1% (C) Polyoxyethylene (5) hydrogenated castor oil 1.5% Liquid sorbitol (70%) 55% Thickening silica 5.0% Propylene glycol 5.0% Xanthan gum 1.0% Sodium alginate 0.8% Sodium polyacrylate 0.6% Sodium fluoride 0.32% Sodium lauryl sulfate 1.5% Sodium sulfate 0.5% Sodium saccharin 0.09% Citric acid 0.3% Sodium citrate 0.5% Flavoring 0.98% Purified water Balance Total 100%

[0090] Formulation Example 3 A mouthwash composition having the following composition was prepared according to the following procedure: (A) Phellodendron Bark Extract (berberine content 5%) 0.05% (B) Sodium tetradecene sulfonate 0.1% (C) Polyoxyethylene (60) hydrogenated castor oil 0.5% Ethanol 8% Sorbitol 7% Propylene glycol 4% Citric acid 0.05% Sodium citrate 0.3% Fragrance 0.2% Purified water Balance Total 100%

[0091] <Method for preparing mouthwash composition> First, components (A), (B), and other water-soluble components were mixed and dissolved in purified water at room temperature (mixture P). Next, component (C) and a fragrance were mixed and dissolved in propylene glycol at room temperature (mixture Q). Mixture Q was added to and mixed with mixture P while stirring to obtain a mouthwash composition.

[0092] Formulation Example 4 A mouthwash composition having the following composition was prepared in the same manner as in Formulation Example 3. (A) Phellodendron Bark Extract (berberine content 5%) 0.06% (B) Sodium tetradecene sulfonate 0.2% (C) Polyoxyethylene (60) hydrogenated castor oil 1% Glycerin 8% Propylene glycol 3% Citric acid 0.03% Sodium citrate 0.25% Fragrance 0.1% Purified water Balance Total 100%

[0093] Formulation Example 5 A mouthwash composition having the following composition was prepared according to the following procedure: (A) Phellodendron Bark Extract (berberine content 5%) 0.05% (B) Sodium Tetradecene Sulfonate 0.1% (C) Polyoxyethylene (60) Hydrogenated Castor Oil 0.5% Glycerin 10% Hydroxyethylcellulose 0.3% Propylene Glycol 5% Fragrance 0.5% Purified Water Balance Total 100%

[0094] <Method for preparing mouthwash composition> First, components (A), (B), and other water-soluble components were mixed and dissolved in purified water at room temperature (mixture R). Next, component (C) and a flavor were mixed and dissolved in propylene glycol at room temperature (mixture S). Mixture S was added to and mixed with mixture R while stirring to obtain a mouthwash composition.

[0095] According to the present invention, an oral composition having excellent selective antibacterial activity against pathogenic bacteria in the oral cavity can be provided.

Claims

1. An oral composition comprising: (A) component: at least one selected from the group consisting of berberine, its salts, plants containing berberine or its salts, and extracts thereof; and (B) component: sodium tetradecene sulfonate, wherein when the mass of component (A) converted into berberine is A and the mass of component (B) is B, the ratio represented by B / A is 20 to 200.

2. An oral composition as described in claim 1, further comprising a component (C): a nonionic surfactant, wherein when the mass of the component (C) is C, the ratio represented by C / the ...

3. The oral composition according to claim 2, wherein the component (C) is at least one selected from the group consisting of polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, sorbitan fatty acid ester, and polyglycerin fatty acid ester.

4. An oral composition according to any one of claims 1 to 3, which is used for improving the oral flora.