Oral composition

Abstract

To provide a composition for oral cavity hardly causing separation during preservation while containing a slightly water-soluble medicinal component.SOLUTION: This composition for the oral cavity comprises (A) sodium fluoride, (B) a water-soluble calcium salt, (C) one or more kinds selected from the group consisting of condensed phosphoric acids and their alkali metal salts and (D) one or more kinds selected from the group consisting of tocopherol, glycyrrhetinic acid, Phellodendron amurense RUPRECHT extract and hinokitiol.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an oral composition. [Background technology]

[0002] Known medicinal ingredients that can be incorporated into oral compositions such as dentifrices include, for example, tocopherol, glycyrrhetinic acid salts, Phellodendron bark extract, and hinokitiol (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Publication No. 2022-000420 Summary of the Invention [Problem to be solved by the invention]

[0004] However, since these components are poorly water-soluble, it is not easy to stably incorporate them into the oral composition, and separation may occur during storage of the oral composition. An object of the present invention is to provide an oral composition that contains a poorly water-soluble medicinal ingredient and is less likely to separate during storage. [Means for solving the problem]

[0005] The present invention has the following aspects. [1] An oral composition containing (A) sodium fluoride, (B) a water-soluble calcium salt, (C) one or more members selected from the group consisting of condensed phosphoric acid and salts thereof, and (D) one or more members selected from the group consisting of tocopherol and derivatives thereof, glycyrrhetinic acid and derivatives thereof, Phellodendron bark extract, and hinokitiol. [2] The oral composition according to [1], wherein the component (B) comprises one or more selected from the group consisting of calcium chloride, calcium glycerophosphate, calcium gluconate, calcium lactate, and calcium pantothenate. [3] The oral composition according to [1] or [2], wherein the component (C) comprises one or more selected from the group consisting of alkali metal pyrophosphates, alkali metal tripolyphosphates, and alkali metal hexametaphosphates. [4] The oral composition according to [3], wherein the component (C) comprises one or more selected from the group consisting of alkali metal pyrophosphates. [5] The oral composition according to any one of [1] to [4], wherein D / (A+B+C), which represents the mass ratio of the content of the (D) component to the total content of the (A) component, the (B) component, and the (C) component, is 0.007 to 1.5. [6] The oral composition according to any one of [1] to [5], which is a dentifrice. [Effects of the Invention]

[0006] According to the present invention, an oral composition is obtained which contains a poorly water-soluble medicinal ingredient and is less likely to separate during storage. DETAILED DESCRIPTION OF THE INVENTION

[0007] As used herein, "oral composition" means a composition intended primarily for use in the oral cavity. In this specification, "water-soluble" means that the solubility in water at 20°C is 1 g / 100 g or more. In this specification, the use of "to" to indicate a range of values ​​means that the values ​​before and after it are included as the lower and upper limits.

[0008] [Oral composition] The oral composition of the present invention contains component (A), component (B), component (C), and component (D).

[0009] <Component (A)> Component (A) is sodium fluoride (NaF). Component (A) contributes to preventing separation of the oral composition. Commercially available products can be used as component (A).

[0010] <(B) component> Component (B) is a water-soluble calcium salt. Component (B) contributes to preventing separation of the oral composition. Additionally, component (B) contributes to the stability of component (D) in the oral composition. Component (B) can be a commercially available product. Examples of component (B) include calcium chloride, calcium nitrate, calcium acetate, calcium citrate, calcium glycerophosphate, calcium gluconate, calcium benzoate, calcium formate, calcium fumarate, calcium lactate, calcium butyrate, calcium isobutyrate, calcium malate, calcium maleate, calcium propionate, calcium valerate, and calcium pantothenate. The component (B) may be one type alone or a combination of two or more types.

[0011] The component (B) preferably contains a component (B1) which is one or more members selected from the group consisting of calcium chloride, calcium glycerophosphate, calcium gluconate, calcium lactate, and calcium pantothenate. The proportion of the (B1) component relative to the total mass of the (B) component may be, for example, 90 mass% or more, 95 mass% or more, 96 mass% or more, 97 mass% or more, 98 mass% or more, or 99 mass% or more, or may be 100 mass%.

[0012] <(C) component> The component (C) is at least one selected from the group consisting of condensed phosphoric acid and salts thereof. Two or more types of component (C) may be combined. Component (C) contributes to preventing separation of the oral composition. Commercially available products can be used as component (C).

[0013] As the condensed phosphoric acid or a salt thereof, a water-soluble condensed phosphoric acid or a salt thereof can be preferably used. Examples of condensed phosphoric acid include linear polyphosphoric acids such as pyrophosphoric acid, tripolyphosphoric acid, and tetrapolyphosphoric acid; and cyclic polyphosphoric acids such as trimetaphosphoric acid, tetrametaphosphoric acid, and hexametaphosphoric acid. As the salt of condensed phosphoric acid, an alkali metal salt is preferred, and examples thereof include a sodium salt and a potassium salt. In particular, from the viewpoint of suppressing separation, alkali metal pyrophosphate, alkali metal tripolyphosphate, and alkali metal hexametaphosphate are preferred, alkali metal pyrophosphate and alkali metal tripolyphosphate are more preferred, and alkali metal pyrophosphate is even more preferred. Specifically, potassium pyrophosphate and sodium pyrophosphate are particularly preferred.

[0014] Component (C) preferably includes component (C1), which is one or more alkali metal pyrophosphates. The proportion of the (C1) component relative to the total mass of the (C) component may be, for example, 90 mass% or more, 95 mass% or more, 96 mass% or more, 97 mass% or more, 98 mass% or more, or 99 mass% or more, or may be 100 mass%.

[0015] <(D) component> Component (D) is one or more selected from the group consisting of tocopherol and its derivatives, glycyrrhetinic acid and its derivatives, Phellodendron bark extract, and hinokitiol. Component (D) may be a combination of two or more. Component (D) is a medicinal ingredient.

[0016] Tocopherol can be incorporated in the form of tocopherol or a derivative thereof. The derivative can be an ester of tocopherol with an organic acid or a salt thereof. Tocopherol is a medicinal ingredient that activates the gums by promoting blood flow and tissue repair, and is an effective ingredient for preventing or suppressing periodontal diseases such as gingivitis and periodontitis. Examples of tocopherols include d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol. Examples of tocopherol derivatives or salts thereof include esters of tocopherol with organic acids (acetic acid, nicotinic acid, succinic acid, linolenic acid, etc.) and alkali metal salts thereof, such as sodium and calcium salts. Specific examples include d-α-tocopherol acetate, dl-α-tocopherol acetate, d-α-tocopherol nicotinate, dl-α-tocopherol nicotinate, d-α-tocopherol succinate, dl-α-tocopherol succinate, tocopherol calcium succinate, d-α-tocopherol linolenate, and dl-α-tocopherol linolenate. Among these, tocopherol, tocopherol acetate, and tocopherol nicotinate are preferred, with tocopherol acetate being more preferred, particularly in terms of the color and appearance of the formulation. These derivatives may be used alone or in combination of two or more. Tocopherol or its derivatives that comply with the Japanese Pharmacopoeia (JP), the former Standards for Cosmetic Ingredients (SYO), or the Foreign Ingredients Standards can be used. Specifically, commercially available products manufactured by DSM Nutrition Japan, Eisai Food & Chemical Co., Ltd., BASF Japan Ltd., etc. can be used.

[0017] Glycyrrhetinic acid can be blended in the form of glycyrrhetinic acid or its derivatives. As the derivative, an ester of glycyrrhetinic acid with an alcohol or a salt thereof can be used. Glycyrrhetinic acid has anti-inflammatory effects and is effective in preventing gingivitis and periodontal disease in the oral cavity. Specific examples include β-glycyrrhetinic acid, glyceryl β-glycyrrhetinate, stearyl β-glycyrrhetinate, pyridoxine β-glycyrrhetinate, etc. In terms of anti-inflammatory effect, β-glycyrrhetinic acid is particularly preferred. As β-glycyrrhetinic acid or a derivative thereof, commercially available products such as β-glycyrrhetinic acid manufactured by Maruzen Pharmaceutical Co., Ltd. can be used.

[0018] Phellodendron bark extract is a solvent extract of plants containing Phellodendron bark (Phellodendron bark), and is a medicinal ingredient with anti-inflammatory, antibacterial, etc. Phellodendron bark extract may be in liquid form, or may be in a dried solid form, or a powdered extract may be used. For example, Phellodendron Bark Powder listed in the 18th Revised Japanese Pharmacopoeia and Phellodendron Bark Extract listed in the Quasi-drug Raw Materials Standards 2021 can be used, and commercially available products can also be used. Examples of commercially available products include Phellodendron Bark Extract S, a product name manufactured by Ogi Pharmaceutical Co., Ltd., and Phellodendron Bark Extract-J, a product name of a liquid extract containing ethanol, manufactured by Maruzen Pharmaceutical Co., Ltd.

[0019] Hinokitiol is a crystalline acidic compound unique to the natural tree Aomori Hiba. Other tree species containing hinokitiol include Taiwanese cypress and North American Western red cedar. Hinokitiol has strong antibacterial activity and a broad antibacterial spectrum, making it one of the few natural fungicides and a medicinal ingredient effective in preventing or improving periodontal disease. Hinokitiol is also available as a chemically synthesized product, and both natural and synthetic products may be used in the present invention. Such hinokitiol is widely and commonly used in foods, cosmetics, pharmaceuticals, agricultural products, building materials, feed, and other applications. Commercially available products used in these applications may be used in the present invention.

[0020] <Content of each ingredient> The content of component (A) is preferably 0.09 to 1.3% by mass, more preferably 0.10 to 1.1% by mass, based on the total mass of the oral composition. When the content of component (A) is within the above range, the effect of inhibiting separation of the oral composition is more excellent. When the content of component (A) is equal to or less than the above upper limit, the stability of component (D) in the oral composition is more excellent.

[0021] The content of component (B) is preferably 0.02 to 5.0% by mass, more preferably 0.03 to 3.0% by mass, based on the total mass of the oral composition. When the content of component (B) is within the above range, the effect of inhibiting separation of the oral composition is more excellent. When the content of component (B) is equal to or greater than the above lower limit, the stability of component (D) in the oral composition is more excellent.

[0022] The content of component (C) is preferably 0.02 to 3.0% by mass, and more preferably 0.03 to 1.3% by mass, relative to the total mass of the oral composition. When the content of component (C) is within the above range, the oral composition exhibits a more excellent effect of inhibiting separation.

[0023] The content of component (D) is preferably 0.001 to 1% by mass relative to the total mass of the oral composition. When the content of component (D) is equal to or greater than the above-mentioned lower limit, the medicinal effect is superior. When the content of component (D) is equal to or less than the above-mentioned upper limit, the stability of component (D) in the oral composition is superior. In this specification, the content of component (D) is the content of the pure component excluding solvents, etc. For example, the content of Phellodendron Bark extract is the content of the pure extract excluding the solvent.

[0024] The content of tocopherol is preferably 0.01 to 1% by mass relative to the total mass of the oral cavity composition. The content of glycyrrhetinic acid and its derivatives is preferably 0.001 to 0.2% by mass relative to the total mass of the oral composition. The content of the Phellodendron Bark extract is preferably 0.01 to 0.3 mass %, more preferably 0.02 to 0.25 mass %, and even more preferably 0.05 to 0.2 mass %, relative to the total mass of the oral cavity composition. The content of hinokitiol is preferably 0.005 to 0.5% by mass, more preferably 0.01 to 0.2% by mass, relative to the total mass of the oral cavity composition.

[0025] D / (A+B+C), which represents the mass ratio of the content of component (D) to the total content of components (A), (B), and (C), is preferably 0.007 to 1.5, and more preferably 0.062 to 1.12.

[0026] <Water> The oral composition typically further contains water, such as purified water, sterilized purified water, and water for injection. The content of water in the oral composition can be appropriately set depending on the product form and method of use of the oral composition. For example, when the oral composition is a toothpaste, the content of water relative to the total mass of the oral composition is preferably 5 to 90 mass%, more preferably 10 to 60 mass%, and even more preferably 20 to 50 mass%.

[0027] <Other ingredients> The oral composition may further contain other components in addition to the components (A), (B), (C), (D) and water. The other components can be appropriately selected from known components taking into consideration the form and method of use of the oral composition. Examples of other components include abrasives, binders, thickeners, surfactants, colorants, sweeteners, preservatives, flavorings, medicinal ingredients other than component (D), pH adjusters, and water-miscible organic solvents. A water-miscible organic solvent is an organic solvent that dissolves 25 g or more in 1 L of water at 25°C.

[0028] As the surfactant, any surfactant known in oral compositions can be used, including, for example, a nonionic surfactant, an amphoteric surfactant, an anionic surfactant, etc.

[0029] 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, polyoxyethylene polyoxypropylene fatty acid esters, polyoxyethylene polyoxypropylene (EOPO) copolymers, alkyl glucosides, and fatty acid polyglyceryl. The alkyl group of the polyoxyethylene alkyl ether usually has 12 to 18 carbon atoms, preferably 14 to 18 (for example, lauryl or stearyl group), and the average number of moles of ethylene oxide added is usually 5 to 30 moles, preferably 15 to 30 moles. The average number of moles of ethylene oxide added in polyoxyethylene hydrogenated castor oil is usually 5 to 100 moles, preferably 20 to 100 moles, and more preferably 20 to 60 moles. The number of carbon atoms in the fatty acid of the sorbitan fatty acid ester is usually 12 to 18. The number of carbon atoms in the fatty acid of the polyoxyethylene sorbitan fatty acid ester is usually 16 to 18, and the average number of moles of ethylene oxide added is usually 10 to 40 moles. The alkyl chain of the alkylolamide usually has 12 to 14 carbon atoms. The polyoxyethylene polyoxypropylene (EOPO) copolymer preferably has an average number of moles of ethylene oxide added of 20 to 210 and an average number of moles of propylene oxide added of 15 to 60, and may be a block copolymer or a random copolymer.

[0030] Examples of amphoteric surfactants include betaine-type amphoteric surfactants and amino acid-type amphoteric surfactants. Examples of betaine-type amphoteric surfactants include fatty acid amidopropyl betaines (e.g., coconut oil fatty acid amidopropyl betaine), alkyl acetate betaines (e.g., alkylamino acetate betaines such as lauryl dimethylamino acetate betaine), and alkyl imidazolinium betaines (e.g., alkylcarboxymethyl hydroxyethyl imidazolinium betaine). Among these, fatty acid amidopropyl betaines and alkyl acetate betaines are preferred, and coconut oil fatty acid amidopropyl betaine is more preferred. When the amphoteric surfactant has an alkyl group or an acyl group, they may be either linear or branched, and may be either saturated or unsaturated. The number of carbon atoms in the alkyl group or acyl group is preferably 10 to 20, more preferably 12 to 18, and even more preferably 14 to 16.

[0031] Examples of anionic surfactants include alkyl sulfates (e.g., sodium dodecyl sulfate (SDS)), α-olefin sulfonates (AOS), lauroyl methyl taurine (LMT), sulfosuccinic acid, GluNa, and alaninate. The alkyl group and acyl group may be either linear or branched, and may be either saturated or unsaturated. The number of carbon atoms in the alkyl group or acyl group is, for example, preferably 10 to 20, more preferably 12 to 18, and even more preferably 14 to 16. The salt can be selected from pharmacologically acceptable salts. Examples of pharmacologically acceptable salts include base addition salts and amino acid salts. Examples of salts include inorganic base salts such as sodium salt, potassium salt, calcium salt, magnesium salt, and ammonium salt; organic base salts such as triethylammonium salt, triethanolammonium salt, pyridinium salt, and diisopropylammonium salt; and basic amino acid salts such as arginine salt. Among these, inorganic base salts are preferred, alkali metal salts (e.g., sodium salt, potassium salt) or ammonium salts are more preferred, and sodium salts are even more preferred.

[0032] When the oral composition contains a surfactant, the content of the surfactant is preferably 0.05 to 10.0% by mass, more preferably 0.1 to 8.0% by mass, relative to the total mass of the oral composition.

[0033] Examples of abrasives include silica-based abrasives such as silicic acid anhydride, precipitated silica, silica gel, aluminosilicate, and zirconosilicate; dibasic calcium phosphate dihydrate or anhydrate, monobasic calcium phosphate, tribasic calcium phosphate, tetrabasic calcium phosphate, calcium carbonate, calcium hydroxide, aluminum hydroxide, insoluble sodium metaphosphate, tribasic magnesium phosphate, and magnesium carbonate. Silica-based abrasives are particularly preferred. The content of the abrasive is, for example, preferably 0 to 60% by mass, more preferably 0 to 30% by mass, and may be 25% by mass or less, relative to the total mass of the oral composition. An abrasive content of 0% by mass means that no abrasive is contained.

[0034] Examples of binders include organic binders selected from water-soluble polymeric substances such as cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, and hydroxyethylcellulose; gums such as xanthan gum, tragacanth gum, karaya gum, and gum arabic; and polyacrylates such as sodium polyacrylate; and inorganic binders such as thickening silica, thickening aluminum silica, Veegum, and Laponite. The content of the binder is preferably, for example, 0.05 to 13.0% by mass relative to the total mass of the oral composition. When the binder contains an organic binder, the blending amount of the organic binder is more preferably 0.1 to 3 mass %, and even more preferably 0.5 to 2.5 mass %, relative to the total mass of the oral composition. When the binder contains an inorganic binder, the content of the inorganic binder is more preferably 0 to 10.0 mass %, and even more preferably 0 to 8.0 mass %, relative to the total mass of the oral composition, in terms of the adsorption of fluoride ions to the tooth surface.

[0035] Examples of thickening agents include sugar alcohols such as sorbitol, xylitol, erythritol, and maltitol, and polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol having an average molecular weight of 160 to 400 (average molecular weight according to the Quasi-drug Raw Materials Standards 2006). The content of the thickener is, for example, preferably 20 to 70% by mass, more preferably 25 to 65% by mass, relative to the total mass of the oral composition.

[0036] Examples of colorants include Red No. 2, Red No. 3, Red No. 225, Red No. 226, Yellow No. 4, Yellow No. 5, Yellow No. 205, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 204, Green No. 3, titanium mica, and titanium oxide. Examples of sweeteners include saccharin sodium, aspartame, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidin dihydrochalcone, and perillartine. Examples of preservatives include parahydroxybenzoic acid esters such as methylparaben, ethylparaben, and butylparaben, and benzoic acid or a salt thereof such as sodium benzoate.

[0037] Examples of fragrances include peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint 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, and grapefruit oil. Natural fragrances such as citrus oil, sweetie oil, yuzu oil, iris concrete, peppermint absolute, rose absolute, orange flower, and processed fragrances (front distillation, tail distillation, liquid-liquid extraction, essence, powder fragrance, etc.) of these natural fragrances, menthol, carvone, anethole, cineole, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linalyl aqua Examples of flavoring materials that can be used include single flavors such as acetate, limonene, menthone, menthyl acetate, N-substituted-paramenthan-3-carboxamide, pinene, octyl aldehyde, citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methylphenyl glycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cyclotene, furfural, trimethylpyrazine, ethyl lactate, and ethyl thioacetate, and compound flavors 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. These flavoring materials can also be used in combination with other flavoring materials known for oral compositions. The content of the flavoring material is not particularly limited, but the content of the above-mentioned flavoring material is preferably 0.000001 to 1% by mass relative to the total mass of the oral composition. The content of the flavoring material used for flavoring is preferably 0.05 to 2% by mass relative to the total mass of the oral composition.

[0038] Examples of medicinal ingredients other than component (D) include disinfectants such as isopropylmethylphenol and cetylpyridinium chloride, water-soluble phosphate compounds such as potassium and sodium orthophosphate (excluding component (C)), enzymes such as dextranase, mutanase, amylase, and protease, tranexamic acid, epsilon aminocaproic acid, triclosan, lysozyme chloride, aluminum chlorohydroxyallantoin, ascorbic acid, dihydrocholesterol, α-bisabolol, chlorhexidine salts, azulene, water-soluble copper compounds such as copper chlorophyllin sodium, chlorophyll, and copper gluconate, aluminum lactate, strontium chloride, potassium nitrate, hydroxamic acid or a derivative thereof, glycyrrhizic acid or a salt thereof, and anti-tartar agents. The above medicinal ingredients can be incorporated in effective amounts within a range that does not interfere with the effects of the present invention.

[0039] An example of a pH adjuster is sodium hydroxide.

[0040] <Form, dosage form> The oral composition can be prepared in various forms, for example, liquid, paste, gel, or solid. The dosage form of the oral composition is not particularly limited. The dosage form of the oral composition is typically an oral preparation that is expelled from the oral cavity after use. Examples of oral preparations include dentifrices (liquid dentifrices, liquid dentifrices, toothpastes, lubricating dentifrices, powder dentifrices, etc.), mouthwashes, mouthwashes, liniments, mouth sprays, patches, sheets, oral sustained-release agents, chewable agents, oral dissolving agents, oral disintegrating agents, tongue care agents, mouth fresheners, denture care agents, etc. Among the above, the oral composition of the present embodiment is suitable as a dentifrice, and is particularly suitable as a toothpaste.

[0041] The oral composition of this embodiment can be prepared by a known method. For example, it can be prepared by mixing components (A), (B), (C), and (D), and other components as necessary, by a known method. For example, the oral composition may be prepared by separately preparing a first phase in which a water-soluble component is dissolved in water and a second phase in which an oil-soluble component is dissolved using a water-miscible organic solvent, and then mixing these phases.

[0042] In the oral composition, fluoride ions, calcium ions, and phosphorus ions form a complex, and it is believed that this complex contributes to preventing separation. The formation of the complex can be confirmed by observing the crystallite size by X-ray crystal structure analysis and the exothermic peak observed when water of crystallization near the phosphate group is released at around 450 °C by calorimetry (TG-DTA measurement). In other words, when the complex is formed, the crystallite size determined from the diffraction peaks attributable to CaF2 becomes less than 10 nm due to the complexation with the phosphate group. Furthermore, the appearance of a peak for water of crystallization indicates that the CaF2 observed in X-ray crystal structure analysis is not a crystal composed only of calcium and fluoride ions, but forms a complex in which the phosphate group interacts. Specifically, the formation of a complex is confirmed by the fact that the crystallite size is less than 10 nm as determined by the following method (1) and the presence of an exothermic peak at 450°C as determined by the following method (2). (1) Crystallite size The sample was measured using an X-ray structural diffractometer (light source Cu:Kα, 40 kV, 20 mA, divergence slit 1 / 2 deg, scattering slit 1 / 2 deg, receiving slit 0.15 mm, scan speed 4,000° / min, 2θ = 2,000 to 80,000°), and the crystallite diameter was calculated using the following formula (Scherrer's formula) to evaluate whether or not a complex was formed. L=Kλ / (βcosθ) L: crystallite diameter, K: coefficient 0.9, β: half-width, λ: 1.54056 Å, θ: diffraction angle (2) TG-DTA measurement (exothermic peak) Heating speed: 5℃ / min, Measurement range: 25℃~600℃

[0043] The method for forming the above-mentioned complex is not particularly limited, but when preparing the oral composition, it is preferable to adopt, for example, a process of blending component (A) and component (C) and then blending component (B), or a process of blending component (B) and component (C) and then blending component (A). Note that if component (A) and component (B) are blended simultaneously, calcium fluoride may be partially produced, which may result in a lower efficiency of complex formation.

[0044] The oral composition described above contains component (A), component (B), component (C), and component (D), and therefore provides the medicinal effect of component (D) while suppressing separation of component (D) even while containing it. [Example]

[0045] The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following description. In the following examples, the unit of content "%" refers to "% by mass" unless otherwise specified.

[0046] <Raw materials used> [Component (A)] Sodium fluoride: manufactured by Stella Chemifa Co., Ltd. Also referred to as "NaF" hereinafter.

[0047] [(B) Component] Calcium glycerophosphate: manufactured by Iwaki Pharmaceutical Co., Ltd. Hereinafter also referred to as "calcium glycerophosphate." Calcium lactate hydrate: trade name "Calcium lactate" manufactured by Taihei Chemical Industry Co., Ltd. Also referred to as "Ca lactate" hereinafter. Calcium gluconate: manufactured by Fuso Chemical Co., Ltd. Hereinafter also referred to as "Calcium gluconate." Calcium chloride: manufactured by Tomita Pharmaceutical Co., Ltd. Hereinafter also referred to as "Ca chloride." Calcium pantothenate: manufactured by BASF. Hereinafter also referred to as "Ca pantothenate."

[0048] [(C) component] Tetrapotassium pyrophosphate: manufactured by Taihei Chemical Industry Co., Ltd. Hereinafter also referred to as "K pyrophosphate." Sodium pyrophosphate: Taihei Chemical Industry Co., Ltd., product name "Sodium pyrophosphate (anhydrous)". Hereinafter, also referred to as "Na pyrophosphate". Sodium tripolyphosphate: manufactured by Taihei Chemical Industry Co., Ltd. Hereinafter also referred to as "sodium tripolyphosphate."

[0049] [(D) component] Tocopherol: Manufactured by DSM Nutrition Japan Co., Ltd., product name "Tocopherol acetate". Glycyrrhetinic acid: Manufactured by Maruzen Pharmaceutical Co., Ltd., product name "β-glycyrrhetinic acid". Phellodendron Bark Extract: Manufactured by Ogi Pharmaceutical Co., Ltd., product name: Phellodendron Bark Extract S (berberine content 5%). Hinokitiol: Manufactured by Takasago Chemical, product name "Hinokitiol".

[0050] [Fragrance] Fragrance composition A as described in Table 5 below. [water] Purified water. [Common component (arbitrary component)] Silica anhydride (abrasive silica) 10%, sorbitol solution (70% concentration, thickener) 40%, propylene glycol (thickener, water-miscible organic solvent) 3%, xanthan gum (binder) 0.5%, polyoxyethylene hydrogenated castor oil (average number of ethylene oxide added: 5 moles) 1%, coconut oil amidopropyl betaine 0.5%, and saccharin sodium (sweetener) 0.2%. Total 55.2%.

[0051] <Examples 1 to 25 and Comparative Examples 1 to 5> Oral compositions (toothpastes) having the compositions shown in Tables 1 to 4 were prepared by conventional methods. The components were mixed in the following order to prepare a premix: an aqueous solution of component (C), an aqueous solution of component (B), and an aqueous solution of component (A). The amount of water was the amount necessary to achieve the composition shown in the table. Water-soluble components (liquid sorbitol, sodium saccharin) were added and dissolved in this premix to prepare phase A. Meanwhile, xanthan gum, component (D), polyoxyethylene hydrogenated castor oil, and coconut oil amidopropyl betaine were added to propylene glycol, and the mixture was dissolved and dispersed at room temperature to prepare phase B. Phase B was then added and mixed with phase A while stirring to prepare phase C. Silica anhydride was added to phase C, and the mixture was mixed at room temperature using a 1.5 L kneader (manufactured by Ishiyama Machine Works). The mixture was then degassed at a reduced pressure of 4 kPa to obtain 1.0 kg of toothpaste. In each toothpaste, it was confirmed by the above-mentioned method that fluoride ions, calcium ions, and phosphorus ions formed a complex. A blank space in the table indicates that the component is not blended. The "balance" of purified water indicates the amount that makes the total amount of the oral composition 100%. The resulting oral compositions (toothpastes) were evaluated as follows, and the results are shown in the table.

[0052] <Evaluation method> [Separation suppression] Three tube containers (material: 26 mm diameter laminated tube (manufactured by Dai Nippon Printing Co., Ltd.) with 50 g of each dentifrice composition were filled. After storage at 50°C for three months, the dentifrice composition was poured from the tube onto a piece of straw paper to a depth of 15 cm. The presence or absence of dripping from the opening of the tube and the area of ​​the liquid that had seeped out and spread onto the test paper were evaluated according to the following evaluation standard (1). The three tubes were evaluated in the same manner, and the average score was calculated and evaluated according to evaluation standard (2). [Grading Criteria (1)] 5 points: No dripping from the mouth, no seeping onto the test paper. 4 points: No dripping from the opening, seepage onto the test paper, seepage area is 1.0 cm 2 less than. 3 points: No dripping from the opening, and the area of ​​the liquid seeping onto the test paper is 1.0 cm 2 More than 3.0cm 2 less than. 2 points: No dripping from the opening, and the area of ​​the test paper that seeps out is 3.0 cm 2 That's all. 1 point: When the dentifrice composition was squeezed out of the tube, liquid dripped from the opening of the tube. [Grading Criteria (2)] ◎: Average score 4.6 or higher. ○: Average score is 4.3 or more but less than 4.6 points. △: Average score is 4.0 or more but less than 4.3 points. ×: Average score less than 4.0 points.

[0053] [D component stability] Three tube containers (material: 26 mm diameter laminated tubes with an innermost layer made of linear low-density polyethylene (manufactured by Dai Nippon Printing Co., Ltd.)) were filled with 50 g of each dentifrice composition, and a storage test was conducted at 40°C for 6 months. The concentration (unit: mass%) of component (D) in the dentifrice composition before the start of the test and immediately after the test was completed was measured by liquid chromatography, and the residual rate was calculated using the following formula. The obtained residual rates were evaluated according to the following criteria. Residual rate (%) = {(concentration immediately after the end of the test) / (concentration before the start of the test)} x 100 (Evaluation criteria) ◎: Residual rate is 95% or more. 〇: Residual rate is 93% or more but less than 95%. △: Residual rate is 90% or more but less than 93%. ×: Residual rate is less than 90%.

[0054] [Table 1]

[0055] [Table 2]

[0056] [Table 3]

[0057] [Table 4]

[0058] As shown by the above results, the oral compositions of Examples 1 to 25 exhibited good separation inhibition despite containing the poorly water-soluble component (D). In addition, the stability of component (D) was good even when stored at high temperatures. On the other hand, Comparative Example 1, which did not contain the component (A), Comparative Example 2, which did not contain the component (B), Comparative Example 3, which did not contain the component (C), and Comparative Example 5, which did not contain the components (A) to (C), had good stability of the component (D), but insufficient separation inhibition. In Comparative Example 4, which did not contain component (D), no separation of the composition occurred.

[0059] <Prescription example> In all of the following formulation examples, the separation suppression and stability of component D were excellent. <Prescription Example 1: Toothpaste> Sodium fluoride 0.32% Calcium glycerophosphate 0.2% Tetrapotassium pyrophosphate 0.1% Tocopherol acetate 1.0% Silica anhydride 10% Sorbitol solution (70%) 40% Propylene glycol 3% Xanthan gum 0.5% Sodium polyacrylate 0.5% Coconut oil fatty acid amidopropyl betaine 0.5% Sodium saccharin 0.2% Fragrance composition A 1% Purified water remainder

[0060] <Prescription Example 2: Liquid toothpaste> Sodium fluoride 0.32% Calcium glycerophosphate 0.2% Tetrapotassium pyrophosphate 0.1% Tocopherol acetate 0.1% Glycerin 7.5% Propylene glycol 3% Sorbitol solution (70%) 5% Coconut oil fatty acid amidopropyl betaine 0.3% Fragrance composition A 0.2% Purified water remainder

[0061] <Prescription Example 3: Mouthwash> Sodium fluoride 0.1% Calcium glycerophosphate 0.5% Tetrapotassium pyrophosphate 0.1% Tocopherol acetate 0.1% Glycerin 3% Propylene glycol 2% Sorbitol solution (70%) 3% Fragrance composition A 0.2% Purified water remainder

[0062] Furthermore, toothpastes, liquid toothpastes, and mouthwashes were prepared with the same compositions as in Examples 1 to 25 and the above-mentioned Formulation Examples 1 to 3, except that flavor compositions B to P shown in Tables 5 and 6 below were used instead of flavor composition A. All of these showed good separation inhibition and good stability of component D. The compositions of flavors 1 to 7 and solvents described in Tables 5 and 6 are shown in Tables 7 to 14. In the table, "cut a% of the front end" means that the first a% is removed when the essential oil is distilled, and "cut b% of the front and back ends" means that the first b% and the last b% are removed when the essential oil is distilled.

[0063] [Table 5]

[0064] [Table 6]

[0065] Table 7

[0066] Table 8

[0067] Table 9

[0068] Table 10

[0069] Table 11

[0070] Table 12

[0071] Table 13

[0072] Table 14

Claims

1. (A) sodium fluoride, (B) a water-soluble calcium salt, (C) one or more selected from the group consisting of condensed phosphoric acid and salts thereof, and (D) one or more selected from the group consisting of tocopherol and derivatives thereof, glycyrrhetinic acid and derivatives thereof, Phellodendron Bark extract, and hinokitiol; An oral composition comprising:

2. 2. The oral composition according to claim 1, wherein the component (B) comprises one or more selected from the group consisting of calcium chloride, calcium glycerophosphate, calcium gluconate, calcium lactate, and calcium pantothenate.

3. 2. The oral composition according to claim 1, wherein the component (C) comprises at least one selected from the group consisting of alkali metal pyrophosphates, alkali metal tripolyphosphates, and alkali metal hexametaphosphates.

4. The oral composition according to claim 3, wherein the component (C) comprises one or more members selected from the group consisting of alkali metal pyrophosphates.

5. 2. The oral composition according to claim 1, wherein D / (A+B+C), which represents the mass ratio of the content of the (D) component to the total content of the (A), (B), and (C) components, is 0.007 to 1.

5.

6. The oral composition according to any one of claims 1 to 5, which is a dentifrice.

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