Oral composition

Abstract

To provide an oral composition having excellent fluoride ion release stability during high-temperature storage, excellent flavor expression, and excellent amino acid stability.SOLUTION: An oral composition comprises: component (A) sodium fluoride; component (B) a water-soluble calcium salt; component (C) at least one selected from the group consisting of pyrophosphoric acid and alkali metal salts thereof; and component (D) a non-sulfur-containing amino acid having a primary amino group.SELECTED DRAWING: None

Description

Technical Field

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

Background Art

[0002] Fluorides such as sodium fluoride have an anti-caries effect and are thus widely used as medicinal components in oral compositions such as dentifrices. To effectively actuate the fluoride, it is effective to retain fluoride ions on the oral mucosa and tooth surfaces for a long time, and it is desirable to leave a large amount of fluoride ions in the oral cavity even after rinsing the oral cavity with water or gargling after use.

[0003] Patent Document 1 proposes a method of mixing a first component containing a soluble calcium source and a second component containing a soluble fluoride, and immediately applying the mixture to tooth tissues as a method capable of enhancing the deposition of fluoride in the oral environment. Patent Document 2 discloses an oral composition having a high fluoride ion retention property in the oral cavity, which contains a complex formed in an aqueous solution containing polyphosphate, a calcium salt, and a fluoride salt.

[0004] On the other hand, it is known to incorporate an amino acid into an oral composition. For example, tranexamic acid and ε-aminocaproic acid have an anti-inflammatory effect on the gums. Patent Document 3 proposes an oral composition containing isopropylmethylphenol, a water-soluble tin salt, and an amino acid. The amino acid is said to act to prevent the aversion to the off-flavor derived from isopropylmethylphenol caused by the combined use of isopropylmethylphenol and the water-soluble tin salt, improve the off-flavor, and ensure a good taste feeling during use.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0006] In the method of Patent Document 1, since fluoride ions directly enter the oral cavity, the fluoride ions are immediately washed away by saliva and do not exhibit a sufficient retention effect, or calcium fluoride precipitates in a short time after the two components are mixed, so that the fluoride ions are not released into the oral cavity and do not exhibit an effect. The composition of Patent Document 2 is excellent in the retention and release properties of fluoride ions, but there is room for improvement in the stability of fluoride ion release over time and the stability of flavor expression (flavor development) during high-temperature storage. Furthermore, when an amino acid is contained in the composition of Patent Document 2, there is room for improvement in the stability of the amino acid depending on the type of amino acid.

[0007] An object of the present invention is to provide an oral composition excellent in the stability of fluoride ion release, flavor development, and amino acid stability during high-temperature storage.

Means for Solving the Problems

[0008] As a result of intensive studies, the present inventors have found that by combining sodium fluoride, a water-soluble calcium salt, pyrophosphoric acid or an alkali metal salt thereof, and a specific amino acid, it is possible to suppress the release of fluoride ions, flavor development, and degradation of amino acids during high-temperature storage. The present invention is based on the above findings and has the following aspects.

[0009] <1> (Component (A)): Sodium fluoride and, (Component (B)): A water-soluble calcium salt, (Component (C)): At least one selected from the group consisting of pyrophosphoric acid and alkali metal salts thereof, (D) Component: a sulfur-free amino acid having a primary amino group, and An oral composition containing <2> The oral composition according to <1>, wherein the (B) component is at least one 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 (C) component is at least one selected from the group consisting of pyrophosphoric acid, sodium pyrophosphate, and potassium pyrophosphate. <4> The oral composition according to any one of <1> to <3>, wherein the (D) component is at least one selected from the group consisting of alanine, glycine, arginine, glutamic acid, tranexamic acid, and ε-aminocaproic acid. <5> The oral composition according to any one of <1> to <4>, wherein the molar ratio of the (B) component to the (D) component is 0.05 to 145. <6> The oral composition according to any one of <1> to <5>, which is a dentifrice.

Advantages of the Invention

[0010] According to the present invention, an oral composition excellent in the stability of fluoride ion release property, flavor development, and amino acid stability during high-temperature storage can be provided.

Modes for Carrying Out the Invention

[0011] In the present specification, the "oral composition" means a composition mainly intended for use in the oral cavity. "Water-soluble" means that the solubility in water at 20 °C is 1 g / 100 g or more. "~" indicating a numerical range means including the numerical values described before and after it as the lower limit value and the upper limit value.

[0012] 〔Oral Composition〕 The oral composition of the present invention contains component (A), component (B), component (C), and component (D).

[0013] <Component (A)> Component (A) is sodium fluoride (NaF). Commercially available products can be used as component (A).

[0014] <Component (B)> Component (B) is a water-soluble calcium salt. When the liquid oral composition contains component (B), it is excellent in the stability of fluoride ion release and the stability of amino acids.

[0015] 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, calcium pantothenate, and the like. As component (B), at least one selected from the group consisting of calcium chloride, calcium glycerophosphate, and calcium lactate is preferable. Component (B) may be used alone or in combination of two or more. Commercially available products can be used as component (B).

[0016] <Component (C)> Component (C) is at least one selected from the group consisting of pyrophosphoric acid and its alkali metal salts. When the oral composition contains component (C), it is excellent in the stability of fluoride ion release and the stability of amino acids.

[0017] Examples of the alkali metal salts include sodium salts and potassium salts. As the component (C), from the viewpoint of fluorine ion retention, at least one selected from the group consisting of pyrophosphoric acid, sodium pyrophosphate, and potassium pyrophosphate is preferable, and at least one selected from the group consisting of potassium pyrophosphate and sodium pyrophosphate is particularly preferable. The component (C) may be used alone or in combination of two or more. Commercially available products can be used as the component (C).

[0018] <(D) component> The component (D) is a sulfur-free amino acid having a primary amino group. The "primary amino group" means a monovalent group represented by "-NH 2 ". The "sulfur-free amino acid" means an amino acid that does not contain a sulfur atom in the molecule. By containing the component (D) in the oral composition, the stability of fluorine ion release and the flavor are excellent.

[0019] Examples of the component (D) include natural amino acids and artificial amino acids. Examples of natural amino acids include acidic amino acids such as aspartic acid and glutamic acid; basic amino acids such as lysine, arginine, and histidine; neutral polar amino acids such as asparagine, glutamine, serine, threonine, and tyrosine; hydrophobic aliphatic amino acids such as alanine, glycine, valine, proline, isoleucine, and leucine; and hydrophobic aromatic amino acids such as phenylalanine and tryptophan. Examples of artificial amino acids include tranexamic acid, ε-aminocaproic acid, D-amino acids, N-methylated amino acids, 2-aminoadipic acid, 3-aminoadipic acid, β-alanine, β-aminopropionic acid, 2-aminobutyric acid, 4-aminobutyric acid, 2-aminoheptanoic acid, 2-aminoisobutyric acid, 3-aminoisobutyric acid, 2-aminopimelic acid, 2,4-diaminobutyric acid, 2,2''-diaminopimelic acid, 2,3-diaminopropionic acid, N-ethylglycine, N-ethylasparagine, hydroxylysine, allo-hydroxylysine, 3-hydroxyproline, 4-hydroxyproline, isodesmosine, allo-isoleucine, N-methylglycine, sarcosine, N-methylisoleucine, N-methylvaline, norvaline, norleucine, and ornithine.

[0020] Among the above, from the viewpoints of amino acid stability and persistence of fluoride ion release property, at least one selected from the group consisting of hydrophobic aliphatic amino acids, hydrophobic aromatic amino acids, tranexamic acid, and ε-aminocaproic acid is preferable. Particularly from the viewpoint of amino acid stability, at least one selected from the group consisting of alanine, glycine, arginine, glutamic acid, tranexamic acid, and ε-aminocaproic acid is preferable. Among these, from the viewpoint of fluoride ion release property, at least one selected from the group consisting of tranexamic acid and ε-aminocaproic acid is particularly preferable. Component (D) may be used alone or in combination of two or more. Commercially available products can be used as component (D).

[0021] <Content of each component> 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 at least the above lower limit value, the stability of fluoride ion release property is more excellent. When the content of component (A) is at most the above upper limit value, the flavor development and the stability of amino acids are more excellent.

[0022] (B) component content 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 (B) component is at least the above lower limit value, the stability of the amino acid is more excellent. When the content of (B) component is at most the above upper limit value, the stability of the fluoride ion release property and the flavor are more excellent.

[0023] (C) component content is preferably 0.02 to 3.0% by mass, more preferably 0.03 to 1.3% by mass, based on the total mass of the oral composition. When the content of (C) component is at least the above lower limit value, the stability of the fluoride ion release property and the stability of the amino acid are more excellent. When the content of (C) component is at most the above upper limit value, the flavor is more excellent.

[0024] (D) component content is preferably 0.01 to 1% by mass, more preferably 0.03 to 0.5% by mass, based on the total mass of the oral composition. When the content of (D) component is at least the above lower limit value, the stability of the fluoride ion release property and the flavor are more excellent. When the content of (D) component is at most the above upper limit value, the stability of the amino acid ((D) component) is more excellent. (D) component content is preferably an amount such that (B) / (D) described below is within the preferred range described below.

[0025] The molar ratio of (B) component to (D) component (hereinafter also referred to as "(B) / (D)") is preferably 0.05 to 145, more preferably 0.1 to 110. When (B) / (D) is at least the above lower limit value, the stability of the amino acid is more excellent. When (B) / (D) is at most the above upper limit value, the stability of the fluoride ion release property and the flavor are more excellent.

[0026] <Other components> The oral composition of the present invention may further contain other components other than (A) component, (B) component, (C) component and (D) component, if necessary, as long as the effects of the present invention are not impaired. Other components can be appropriately selected from known components in consideration of the dosage form, method of use, etc. of the oral composition. Examples of other components include water, abrasive agents, binders, thickeners, surfactants, colorants, sweeteners, preservatives, flavors, active ingredients, and pH adjusters.

[0027] Examples of abrasive agents include silica-based abrasive agents such as anhydrous silicic acid, precipitated silica, silica gel, aluminosilicate, and zirconosilicate; dicalcium phosphate dihydrate and anhydride, monocalcium phosphate, tricalcium phosphate, tetracalcium phosphate, calcium carbonate, calcium hydroxide, aluminum hydroxide, insoluble sodium metaphosphate, magnesium phosphate tribasic, and magnesium carbonate. In particular, silica-based abrasive agents are preferred in terms of the expression of the effects of the present invention. The content of the abrasive agent is preferably 0 to 60% by mass, more preferably 0 to 30% by mass, and may be 25% by mass or less, based on the total mass of the oral composition. The content of the abrasive agent being 0% by mass indicates that no abrasive agent is contained.

[0028] Examples of binders include organic binders selected from water-soluble polymer 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 silicate, Veegum, and laponite. The content of the binder is preferably 0.05 to 13.0% by mass based on 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% by mass, and even more preferably 0.5 to 2.5% by mass, based on 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% by mass, and even more preferably 0 to 8.0% by mass, based on the total mass of the oral composition, in terms of the adsorption property of fluoride ions to the tooth surface.

[0029] Examples of the thickening agent include sugar alcohols such as sorbitol, xylitol, erythritol, and maltitol, polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol with an average molecular weight of 160 to 400 (average molecular weight described in the Pharmaceutical Excipients Standards 2006). The content of the thickening agent is preferably 20 to 70% by mass, more preferably 25 to 65% by mass, based on the total mass of the oral composition.

[0030] Examples of the surfactant include nonionic surfactants, anionic surfactants, and amphoteric surfactants. Examples of the nonionic surfactant include glycerin fatty acid esters such as decaglycerin laurate, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate (average number of moles of ethylene oxide added (hereinafter abbreviated as "E.O.") 20), alkyl glycosides having 12 to 16 carbon atoms in the alkyl group, sorbitan fatty acid esters such as sorbitan tristearate, sucrose fatty acid esters such as sucrose laurate, and polyoxyethylene alkyl ethers such as polyoxyethylene stearyl ether (E.O. 6). Examples of the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, acyl sarcosinates such as sodium lauroyl sarcosinate, acyl amino acid salts such as sodium acyl glutamate, sodium acyl taurine, sodium dodecylbenzenesulfonate, sodium lauryl sulfoacetate, and sodium α-olefin sulfonate. Examples of the amphoteric surfactant include coconut oil fatty acid amide propyl betaine, lauryldimethylaminoacetic acid betaine, and N-coconut oil fatty acid acyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine. The content of the surfactant is preferably 0.05 to 10.0% by mass, more preferably 0.1 to 8.0% by mass, based on the total mass of the oral composition.

[0031] Examples of the coloring agent 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, mica titanium, and titanium oxide. Examples of the sweetener include sodium saccharin, aspartame, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidin dihydrochalcone, and perillartine. Examples of the preservative include paraoxybenzoic acid esters such as methyl paraben, ethyl paraben, and butyl paraben, and benzoic acid or its salts such as sodium benzoate.

[0032] Examples of the fragrance include natural fragrances such as peppermint oil, spearmint oil, anise oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, perilla 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, oregano oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie oil, pomelo oil, iris concrete, absolute peppermint, absolute rose, orange flower, etc., fragrances obtained by processing these natural fragrances (such as cut of the fore fraction, cut of the back fraction, fractional distillation, liquid-liquid extraction, essence formation, powder fragrance formation, etc.), menthol, carvone, anethole, cineole, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted-p-menthane-3-carboxamide, pinene, octyl aldehyde, citral, pregeone, carvyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexanepropionate, methyl anthranilate, ethyl methylphenylglycidate, vanillin, undecalactone, hexanal, butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cyclotene, furfural, trimethylpyrazine, ethyl lactate, ethyl thioacetate and other single fragrances, and compound fragrances such as strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, tropical fruit flavor, etc. A fragrance material known for an oral composition can be used in combination. The content of the fragrance is not particularly limited. For example, it is 0.000001 to 2% by mass based on the total mass of the oral composition. The content of the above fragrance material is preferably 0.000001 to 1% by mass based on the total mass of the oral composition. The content of the fragrance for flavoring using the above fragrance material is preferably 0.05 to 2% by mass based on the total mass of the oral composition.

[0033] Examples of the active ingredient include bactericides such as isopropylmethylphenol and cetylpyridinium chloride, water-soluble phosphate compounds such as potassium salts and sodium salts of orthophosphoric acid (excluding component (C)), enzymes such as dextranase, mutanase, amylase, and protease, tranexamic acid, epsilon-aminocaproic acid, triclosan, lysozyme chloride, aluminum chlorhydroxyallantoin, hinokitiol, ascorbic acid, tocopherol acetate, 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, berberine, hydroxamic acid or its derivatives, glutyl lithium acid or its salts, glycyrrhetinic acid or its derivatives, and calculus inhibitors. The above active ingredients can be blended in an effective amount within a range that does not interfere with the effects of the present invention. The oral composition can contain amino acids other than component (D). From the viewpoint of the stability of the fragrance, the oral composition does not contain sulfur-containing amino acids such as L-cysteine.

[0034] Examples of the pH adjuster include citric acid, tartaric acid, malic acid, and salts such as potassium salts and sodium salts of these acids, and sodium hydroxide.

[0035] <Form, dosage form> The oral composition can be prepared in various forms such as liquid, paste, and 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 discharged from the oral cavity after use. Examples of the oral preparation include dentifrices (liquid dentifrices, liquid dentifrices, paste dentifrices, moist dentifrices, powder dentifrices, etc.), mouthwashes, gargles, coating agents, mouth sprays, patches, sheet agents, sustained-release oral agents, chewing agents, oral dissolving agents, oral disintegrating agents, tongue care agents, oral cooling agents, and denture care agents. Among the above, the oral composition of the present invention is suitable as a dentifrice, and particularly suitable as a paste dentifrice.

[0036] The oral composition of the present invention can be prepared by a known method. For example, it can be prepared by mixing the component (A), component (B), component (C) and component (D), and other components as necessary, in a conventional manner.

[0037] In the oral composition, it is preferable that fluoride ions, calcium ions and phosphate ions form a complex. When the complex is formed, the retention of fluoride ions in the oral cavity is improved, and thereby the adsorption property of fluoride ions to the tooth surface is further improved.

[0038] The formation of the above complex can be confirmed by observing the crystallite size by X-ray crystal structure analysis and the exothermic peak when the crystal water in the vicinity of the phosphate group at around 450 °C desorbs by calorimetry (TG-DTA measurement). That is, when the complex is formed, the crystallite size determined from the diffraction peak attributed to CaF 2 becomes less than 10 nm due to complexation with the phosphate group. Further, the occurrence of the crystal water peak indicates that CaF 2 seen by X-ray crystal structure analysis is not a crystal composed only of calcium and fluoride ions, but forms a complex in which phosphate groups interact. Specifically, the formation of the complex is confirmed by the crystallite size being less than 10 nm by the following method (1) and the presence of an exothermic peak at 450 °C being recognized by the following method (2). (1) Crystallite size The sample was measured with an X-ray structure 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 size was calculated by the following formula (Scherrer's formula) to evaluate the presence or absence of complex formation. L = Kλ / (βcosθ) L: crystallite size, K: coefficient 0.9, β: half-value width, λ: 1.54056 Å, θ: diffraction angle (2) TG-DTA measurement (exothermic peak) Temperature increase speed: 5°C / min, measurement range: 25°C to 600°C

[0039] As a method for forming the above complex, there are no particular limitations. However, when preparing the oral composition, for example, when preparing the oral composition, it is preferable to adopt either the step of blending component (B) after blending components (A) and (C), or the step of blending component (A) after blending components (B) and (C). When components (A) and (B) are blended simultaneously, a part of calcium fluoride may be generated, and the formation efficiency of the complex may be inferior.

[0040] Since the oral composition described above contains component (A), component (B), component (C), and component (D), it is excellent in fluoride ion releasability, flavor development, and amino acid stability during high-temperature storage. Due to the primary amino group of component (D), the charge of the complex of fluoride ion, calcium ion, and phosphorus ion is stabilized, and the amorphous structure of the complex is maintained, so it is considered that the fluoride ion releasability under high-temperature storage is maintained. Conversely, it is considered that component (D) is stabilized by the complex, and the deterioration of component (D) under high-temperature storage is suppressed.

Examples

[0041] Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited by the following description. In the following examples, “%” indicates “mass %” unless otherwise specified.

[0042] <Raw materials used> Sodium fluoride: manufactured by Stella Chemifa Corporation. Hereinafter, it is also referred to as “NaF”. Calcium chloride: manufactured by Tomita Pharmaceutical Co., Ltd. Hereinafter, it is also referred to as “calcium chloride”. Calcium gluconate: manufactured by Fuso Chemical Industry Co., Ltd. Hereinafter, it is also referred to as “calcium gluconate”. Calcium lactate hydrate: manufactured by Taihei Chemical Industry Co., Ltd., trade name “calcium lactate”. Hereinafter, it is also referred to as “calcium lactate”. Calcium glycerophosphate: manufactured by Iwaki Pharmaceutical Co., Ltd. Hereinafter, it is also referred to as “calcium glycerophosphate”. Calcium pantothenate: manufactured by BASF. Hereinafter, it is also referred to as "Ca pantothenate". Potassium pyrophosphate: manufactured by Taihei Chemical Industry Co., Ltd. Hereinafter, it is also referred to as "K pyrophosphate". Sodium pyrophosphate: manufactured by Taihei Chemical Industry Co., Ltd., trade name "Sodium pyrophosphate (anhydrous)". Hereinafter, it is also referred to as "Na pyrophosphate". Sodium tripolyphosphate: manufactured by Taihei Chemical Industry Co., Ltd. Hereinafter, it is also referred to as "Na tripolyphosphate". Tranexamic acid: manufactured by Kyowa Pharmaceutical Chemical Co., Ltd. ε-Aminocaproic acid: manufactured by Daiichi Sankyo Co., Ltd. L-Cysteine: manufactured by Nippon Rikagaku Yakuhin Co., Ltd. Sodium pyrrolidonecarboxylate: manufactured by Ajinomoto Co., Inc. Hereinafter, it is also referred to as "Na pyrrolidonecarboxylate". Alanine: DL-alanine, manufactured by Ajinomoto Health Supply Co., Ltd. Arginine: manufactured by Kanto Chemical Co., Inc. Glycine: manufactured by Kobe Chemical Industry Co., Ltd. Glutamic acid: manufactured by Kanto Chemical Co., Inc.

[0043] <Examples 1 to 29, Comparative Examples 1 to 7> Toothpaste compositions (gel toothpastes) having the compositions shown in Tables 1 to 4 were prepared by a conventional method. An empty cell in the table indicates that the component is not blended. "Remainder" of purified water indicates the amount that makes the total amount of the toothpaste composition 100%. The following evaluations were performed on the obtained toothpaste compositions. The results are also shown in Tables 1 to 4.

[0044] (Stability of fluoride ion release) Each 50 g of the toothpaste composition was filled into three tube containers (material: laminated tube with a diameter of 26 mm made of linear low-density polyethylene for the innermost layer, manufactured by Dainippon Printing Co., Ltd.) and stored at 50°C for 3 months. For the toothpaste compositions before and after storage, the release rate (release amount) of fluoride ions from mucin to saliva was measured by the following procedure, and the stability of fluoride ion release was evaluated. (1) Add 0.2 g of mucin (manufactured by Sigma-Aldrich) to a 10 mL centrifuge tube, and further add 5 mL of the dentifrice composition (40-fold diluted solution with purified water), and let it act for 3 minutes. After washing the mucin with distilled water, treat it with 0.1 N hydrochloric acid for 2 minutes, and measure the fluoride ion concentration contained in the hydrochloric acid with a fluoride ion meter (Orion 1115000 4-Star: manufactured by Thermo Fisher Scientific K.K.), and use that value as the retained fluoride ion concentration. (2) After allowing the dentifrice composition to act on and wash the mucin in the same manner as above, artificial saliva (CaCl 2 = 1.5 mmol / L, KH 2 PO 4 = 5.0 mmol / L, acetic acid = 100 mmol / L, NaCl = 100 mmol / L, the balance = water; pH = 7.0) was added in an amount of 5 mL, stirred for 1 minute, and left standing for 3 minutes, 60 minutes, or 180 minutes to elute the fluoride ions adsorbed and retained by the mucin. Then, centrifuge at 3,000 rpm for 10 minutes each to collect the supernatant, and measure the fluoride ion concentration contained in the solution with a fluoride ion meter (Orion 1115000 4-Star: manufactured by Thermo Fisher Scientific K.K.), and use that value as the released fluoride ion concentration. (3) From the retained fluoride ion concentration and the released fluoride ion concentration, the fluoride ion release rate was calculated by the following formula. Fluoride ion release rate (%) = {Released fluoride ion concentration (ppm) / Retained fluoride ion concentration (ppm)} × 100 (4) From the fluoride ion release rates before and after storage, the retention rate was calculated by the following formula, and the stability of the fluoride ion release property was evaluated according to the following evaluation criteria. Retention rate (%) = {Fluoride ion release rate (%) after storage / Fluoride ion release rate (%) before storage} × 100 [Evaluation criteria] ◎: Retention rate is 97% or more. 〇: Retention rate is 95% or more and less than 97%. △: Retention rate is 93% or more and less than 95%. ×: Retention rate is less than 93%.

[0045] (Stability of amino acids) 50 g of each dentifrice composition was filled into three tube containers (material: laminated tube with a diameter of 26 mm made of linear low-density polyethylene for the innermost layer, manufactured by Dainippon Printing Co., Ltd.), and stored at -5°C for 6 hours and then at 40°C for 6 hours repeatedly for 6 months in a cycle test. The amino acids in each dentifrice composition before and after the cycle test were quantified, and the stability of the amino acids was calculated from the quantified values using the following formula and evaluated according to the following criteria. The quantification of amino acids was performed by liquid chromatography. Amino acid stability (%) = {Amino acid quantification value after cycle test (%) / (Amino acid quantification value before cycle test (%))} × 100 [Evaluation criteria] ◎: Stability is 98% or more. 〇: Stability is 96% or more and less than 98%. △: Stability is 94% or more and less than 96%. ×: Stability is less than 94%.

[0046] (Fragrance intensity) 50 g of each dentifrice composition was filled into three tube containers (material: laminated tube with a diameter of 26 mm made of linear low-density polyethylene for the innermost layer, manufactured by Dainippon Printing Co., Ltd.) and stored at 50°C for 3 months. Ten subjects used the dentifrice composition after storage in the normal way and evaluated the goodness of the fragrance intensity according to the following five-level scoring criteria. The average score of the ten subjects was calculated and judged as ◎, 〇, △, or × according to the following evaluation criteria. [Scoring criteria] 5 points: The fragrance intensity is very good. 4 points: The fragrance intensity is good. 3 points: The fragrance intensity can be felt. 2 points: The fragrance intensity is not very good. 1 point: The fragrance intensity is not good. [Evaluation criteria] ◎: Average score is 4.5 points or more. 〇: Average score is 4.0 points or more and less than 4.5 points. △: Average score is 3.0 points or more and less than 4.0 points. ×: Average score is 1.0 points or more and less than 3.0 points.

[0047]

Table 1A

[0048]

Table 1B

[0049]

Table 2A

[0050]

Table 2B

[0051]

Table 3A

[0052]

Table 3B

[0053]

Table 4A

[0054]

Table 4B

[0055] As shown in the above results, the dentifrice compositions of Examples 1 to 29 were excellent in the stability of fluoride ion release, the stability of amino acids, and the fragrance retention. On the other hand, Comparative Example 1 that did not contain the component (A) was inferior in the stability of fluoride ion release. Comparative Example 2 that did not contain the component (B) was inferior in the stability of fluoride ion release and the stability of amino acids. Comparative Example 3 that did not contain the component (C) was inferior in the stability of fluoride ion release and the stability of amino acids. Comparative Example 4, which does not contain component (D), was inferior in the stability of fluoride ion release and aroma development. Comparative Example 5, which contains sodium tripolyphosphate instead of component (C), was inferior in the stability of fluoride ion release. Comparative Example 6, which contains L-cysteine, a sulfur-containing amino acid, instead of component (D), was inferior in aroma development. Comparative Example 7, which contains sodium pyrrolidone carboxylate, an amino acid having no primary amino group, instead of component (D), was inferior in the stability of amino acids.

[0056] Next, formulation examples are shown. An oral composition having the following composition was prepared by a conventional method and evaluated by the same method as above. As a result, in any of the formulation examples, it was excellent in the stability of fluoride ion release, the stability of amino acids, and aroma development.

[0057] <Formulation Example 1 Toothpaste> Sodium fluoride 0.32% Calcium lactate hydrate 0.2% Sodium pyrophosphate 0.1% Alanine 0.15% Silicic anhydride 10% Sorbitol solution (70%) 40% Propylene glycol 3% Xanthan gum 0.5% Sodium polyacrylate 0.5% Sodium lauryl sulfate 0.5% Saccharin sodium 0.2% Fragrance 1% Purified water balance

[0058] <Formulation Example 2 Toothpaste> Sodium fluoride 0.32% Calcium lactate hydrate 0.2% Sodium pyrophosphate 0.1% Arginine 1.0% Silicic anhydride 10% Sorbitol solution (70%) 40% Propylene glycol 3% Xanthan gum 0.5% Sodium polyacrylate 0.5% Sodium lauryl sulfate 0.5% Sodium saccharin 0.2% Fragrance 1% Purified water balance

[0059] <Formulation Example 3 Toothpaste> Sodium fluoride 0.32% Calcium lactate hydrate 0.2% Sodium pyrophosphate 0.1% Glycine 0.3% Silicic anhydride 10% Sorbitol solution (70%) 40% Propylene glycol 3% Xanthan gum 0.5% Sodium polyacrylate 0.5% Sodium lauryl sulfate 0.5% Sodium saccharin 0.2% Fragrance 1% Purified water balance

[0060] <Formulation Example 4 Toothpaste> Sodium fluoride 0.32% Calcium lactate hydrate 0.2% Sodium pyrophosphate 0.1% Glutamic acid 0.5% Silicic anhydride 10% Sorbitol solution (70%) 40% Propylene glycol 3% Xanthan gum 0.5% Sodium polyacrylate 0.5% Sodium lauryl sulfate 0.5% Sodium saccharin 0.2% Fragrance 1% Purified water balance

[0061] <Formulation Example 5 Toothpaste> Sodium fluoride 0.32% Calcium Glycerophosphate 0.2% Sodium Pyrophosphate 0.1% Arginine 0.1% Silicic Anhydride 10% Sorbitol Solution (70%) 40% Propylene Glycol 3% Xanthan Gum 0.5% Sodium Polyacrylate 0.5% Sodium Lauryl Sulfate 0.5% Saccharin Sodium 0.2% Fragrance 1% Purified Water Balance

[0062] <Formulation Example 6 Toothpaste> Sodium Fluoride 0.32% Calcium Gluconate 0.2% Sodium Polyphosphate 0.1% Arginine 0.1% Silicic Anhydride 10% Sorbitol Solution (70%) 40% Propylene Glycol 3% Xanthan Gum 0.5% Sodium Polyacrylate 0.5% Sodium Lauryl Sulfate 0.5% Saccharin Sodium 0.2% Fragrance 1% Purified Water Balance

Claims

1. Component (A): Sodium fluoride and, Component (B): A water-soluble calcium salt, Component (C): At least one selected from the group consisting of pyrophosphoric acid and its alkali metal salts, Component (D): A non-sulfur-containing amino acid having a primary amino group, An oral composition containing the same.

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

3. The oral composition according to claim 1, wherein the component (C) is at least one selected from the group consisting of pyrophosphoric acid, sodium pyrophosphate, and potassium pyrophosphate.

4. The oral composition according to claim 1, wherein the component (D) is at least one selected from the group consisting of alanine, glycine, arginine, glutamic acid, tranexamic acid, and ε-aminocaproic acid.

5. The oral composition according to claim 1, wherein the molar ratio of the component (B) to the component (D) is 0.05 to 145.

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

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