Oral composition

Abstract

To provide an oral composition that allows allantoin or a derivative thereof to be absorbed well into oral mucosa and has a good taste and a good feeling of use.SOLUTION: An oral composition contains (A) allantoin or a derivative thereof, (B) a polyoxyethylene hardened castor oil with an average number of moles of added ethylene oxide of 5-10 mol, of 0.1-3 mass%, and (C) vitamin E or a derivative thereof of 0.01-3 mass%.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an oral composition which promotes absorption of allantoin or a derivative thereof into oral mucosa such as the gums, has excellent absorbency, is pleasant to eat, and is suitable for preventing or suppressing periodontal diseases such as gingivitis. [Background technology]

[0002] As a water-soluble active ingredient blended in an oral composition, for example, allantoin or a derivative thereof is known to have a tissue repairing effect by activating cell functions, and to be useful in preventing or suppressing periodontal diseases such as gingivitis. In order for this water-soluble active ingredient to act efficiently, it is important that it is absorbed and penetrated into the oral mucosa such as the gingiva. However, unlike the skin, the oral cavity is constantly supplied with saliva and is wet, and oral compositions are often rinsed with water after application to the oral cavity, creating an environment in which it is difficult for water-soluble ingredients to be absorbed and penetrated into the wet mucosal surface of the gingiva or its interior. For this reason, it is difficult to sufficiently promote the absorption of water-soluble active ingredients into the oral mucosal surface of the gingiva or its interior, and in particular, it has been an issue to improve the absorption promotion effect of allantoin or its derivatives, which are unstable and easily decomposed, into the oral mucosa.

[0003] Patent Document 1 (JP Patent Publication No. 2015-205826) proposes adding specific fatty acids or esters to oral compositions to improve the absorption of water-soluble active ingredients into oral tissues. However, there are issues with the feel when used, and it has been proposed that the addition of specific fragrance ingredients would be effective in resolving the lack of refreshing feeling (Patent Document 2; JP Patent Publication No. 2016-222582). Water-insoluble vitamin E or its derivatives, which have a peripheral circulation promoting effect (blood circulation promoting effect) in gingival tissue, are widely used in oral compositions such as dentifrice compositions as an active ingredient for preventing or suppressing periodontal diseases such as gingivitis, and nonionic surfactants contribute to the stable formulation of these, and polyoxyethylene (20) hydrogenated castor oil and the like are widely used due to their good usability. In Patent Document 3 (JP Patent Publication 2017-214297 A), an oil-soluble specific fatty acid or ester is blended to promote the absorption of water-soluble active ingredients in the oral cavity, and further, water-insoluble tocopherol or its derivative is blended with polyoxyethylene alkyl ether, inorganic acid, or alkali metal salt of organic acid, thereby ensuring the storage stability of tocopherol or its derivative and simultaneously blending it, and suppressing the oily odor caused by the specific fatty acid or ester to improve the usability. As described above, the specific fatty acids or esters mentioned above can cause problems with the feel when used depending on the formulation, and there has been a demand for the development of a new technology for promoting absorption of water-soluble active ingredients into the oral mucosa. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2015-205826 A [Patent Document 2] JP 2016-222582 A [Patent Document 3] JP 2017-214297 A [Patent Document 4] JP 2009-149537 A [Patent Document 5] JP 2018-43933 A Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention has been made in consideration of the above circumstances, and an object of the present invention is to provide an oral composition which has excellent absorbability of allantoin or a derivative thereof into the oral mucosa, and which has a good taste and a good feel when used. [Means for solving the problem]

[0006] The present inventors conducted extensive research to achieve the above object, and found that when polyoxyethylene hydrogenated castor oil having an average number of moles of ethylene oxide added of a specific value or less and vitamin E or a derivative thereof are combined in an oral composition containing allantoin or a derivative thereof, the absorption of component (A) into the oral mucosa is promoted, the bitterness is suppressed, and the component (A) can be stably blended even after storage. That is, according to the present invention, an oral composition containing (A) allantoin or a derivative thereof, (B) polyoxyethylene hydrogenated castor oil having an average number of moles of ethylene oxide added of 5 to 10 moles, and (C) vitamin E or a derivative thereof is found to have excellent absorbability of component (A) into the oral mucosa, good taste and good usability, and good storage stability of component (A), leading to the present invention.

[0007] In the present invention, by combining component (A) with component (B), the absorption of component (A) into the oral mucosa was promoted, and it was possible to effectively absorb and penetrate the component. This absorption promotion effect was not obtained when polyoxyethylene hydrogenated castor oil with an average added mole number of ethylene oxide of 20 moles was used instead of component (B), and was an effect specific to component (B). Furthermore, when component (C) was further added, unexpectedly, the bitterness caused by the combined use of components (A) and (B) was suppressed and reduced by component (C), and thus the absorbability of component (A) into the oral mucosa could be increased while maintaining good taste. Therefore, the oral composition of the present invention ensures a pleasant taste while promoting the absorption of component (A) into the oral mucosa, and allows component (A) to be absorbed into the oral mucosa at a high rate. In addition, the storage stability of component (A) is ensured, and the composition can be stably formulated even after storage at high temperatures (50°C), and the pH of the composition can be set to pH 6.4 or less, at which component (A) is relatively stable. In addition, Patent Documents 4 and 5 (JP Patent Publication No. 2009-149537 and JP Patent Publication No. 2018-43933) are related to the improvement of oral mucosa permeability of ascorbic acid phosphate salts by polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 5 to 10, and are effective when the pH of the oral composition is 6.5 or higher. In contrast, the present invention is a technology related to allantoin or its derivatives, which is unstable and easily decomposed, particularly in the basic range, and improves the oral mucosa absorbability of component (A) and suppresses bitterness by components (B) and (C). The above-mentioned action and effect are excellent even when the pH of the oral composition is set to 6.4 or lower, and are rather remarkable at or below the above pH value.

[0008] Accordingly, the present invention provides the following oral compositions. (A) allantoin or a derivative thereof, (B) Polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 5 to 10 moles and (C) Vitamin E or its derivatives An oral composition comprising: Effect of the Invention

[0009] According to the present invention, it is possible to provide an oral composition which has excellent absorbability of component (A) into the oral mucosa, good taste, and storage stability of component (A). The oral composition of the present invention can efficiently exert its medicinal effect by absorbing and penetrating component (A) into the oral mucosa such as the gingiva, and is useful for preventing or suppressing periodontal diseases such as gingivitis. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The present invention will now be described in further detail. The oral composition of the present invention contains (A) allantoin or a derivative thereof, (B) a specific polyoxyethylene hydrogenated castor oil, and (C) vitamin E or a derivative thereof.

[0011] (A) Allantoin or its derivatives have a gum tissue repairing effect and are active ingredients for preventing or suppressing periodontal disease. Examples of allantoin or a derivative thereof include allantoin, allantoin chlorohydroxyaluminum, and allantoin dihydroxyaluminum, and one or more of these can be used.

[0012] The amount of (A) allantoin or its derivative is preferably 0.01 to 0.5% (mass%, the same applies below) of the entire composition, more preferably 0.05 to 0.2%. When the amount is within the above range, the absorbability of (A) component into the oral mucosa is sufficiently promoted and excellent, and the bitterness is sufficiently suppressed. In addition, the storage stability of (A) component can be sufficiently obtained.

[0013] Component (B) is polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide (hereinafter sometimes abbreviated as EO) of 5 to 10 moles, and acts as an absorption enhancer for component (A) into the oral mucosa. The EO of the polyoxyethylene hydrogenated castor oil is 5 to 10 mol, preferably 5 to 7 mol. It is important for the EO to be within the above range in order to promote the absorption of the component (A) into the oral mucosa, and if the EO exceeds 10 mol, the effect of promoting the absorption of the component (A) into the oral mucosa is deteriorated.

[0014] The blending amount of the (B) component is preferably 0.1 to 3% of the total composition, more preferably 0.2 to 2%. When the blending amount is 0.1% or more, the absorption of the (A) component into the oral mucosa is promoted, and the absorbency is sufficiently excellent. When the blending amount is 3% or less, the absorbency is sufficiently excellent, and the bitterness is not too strong, and the bitterness can be sufficiently suppressed.

[0015] (C) Vitamin E or a derivative thereof acts as a bitterness suppressor in a combined system of components (A) and (B). Examples of vitamin E or a derivative thereof that can be used include tocopherols such as d-α-tocopherol, dl-α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol; esters thereof, for example, esters with organic acids such as acetic acid, nicotinic acid, succinic acid, and linoleic acid, particularly esters with organic acids having 1 to 20 carbon atoms; and salts thereof. Specific examples of vitamin E derivatives include tocopherol acetate such as d-α-tocopherol acetate and dl-α-tocopherol acetate, tocopherol nicotinate such as d-α-tocopherol nicotinate and dl-α-tocopherol nicotinate, tocopherol succinate such as d-α-tocopherol succinate and dl-α-tocopherol succinate, tocopherol linolenate such as d-α-tocopherol linolenate and dl-α-tocopherol linolenate, and tocopherol calcium succinate. These may be used alone or in combination of two or more.

[0016] The amount of (C) vitamin E or a derivative thereof is preferably 0.01 to 3% of the total composition, more preferably 0.05 to 2%. When the amount is 0.01% or more, the bitterness is sufficiently suppressed and the taste is good. When the amount is 3% or less, the effect of (B) component is maintained and the absorption promoting effect of (A) component into the oral mucosa is sufficiently excellent.

[0017] Furthermore, the ratio (A) / (B) of the amount of component (A) to component (B) is preferably a mass ratio of 0.005 to 5, more preferably 0.05 to 1. When the mass ratio (A) / (B) is 0.005 or more, absorption of component (A) into the oral mucosa is further promoted, resulting in better absorbency, and when it is 5 or less, bitterness is sufficiently suppressed.

[0018] The ratio (A) / (C) of the amount of the (A) component to the (C) component is preferably 0.01 to 10, more preferably 0.05 to 2, as a mass ratio. When the mass ratio (A) / (C) is within the above range, the absorbability of the (A) component into the oral mucosa is sufficiently excellent, and the bitterness is further suppressed and reduced. When the mass ratio is less than 0.01, the absorbability of the (A) component into the oral mucosa may decrease, and when it exceeds 10, the bitterness may not be sufficiently suppressed.

[0019] Furthermore, (B) / (C), which indicates the ratio of the components (B) and (C), is preferably, in terms of suppressing bitterness, a mass ratio of 0.2 to 60, more preferably 0.2 to 40, and particularly preferably 0.4 to 20. When the mass ratio of (B) / (C) is 60 or less, the bitterness is sufficiently suppressed.

[0020] From the viewpoint of the present action and effect, particularly suppression of bitterness and storage stability of component (A), the oral cavity composition of the present invention preferably has a pH (25° C.) of 4 to 6.4, more preferably 5 to 6. When the pH is 6.4 or lower, the storage stability of component (A) over time is sufficiently ensured, and when the pH is 4 or higher, the bitterness is sufficiently suppressed. A pH adjuster can also be added. Examples of the pH adjuster include citric acid, citric acid or its salts such as sodium citrate, malic acid or its salts, phosphoric acid or its salts, alkali metal hydroxides such as sodium hydroxide, and bicarbonates.

[0021] The oral composition of the present invention can be prepared in the form of a paste, liquid, etc., into a dentifrice composition such as a toothpaste, liquid dentifrice, or lubricant dentifrice, a mouthwash composition, or even a mouth spray, and is particularly suitable as a dentifrice composition or mouthwash composition, especially a dentifrice composition.

[0022] In addition to the above-mentioned components, the oral composition of the present invention may contain known additives (pharmacologically acceptable carriers) and active ingredients that can be used in oral compositions, as long as they do not impair the effects of the present invention. Examples of such additives include abrasives, thickeners, binders, surfactants, sweeteners, preservatives, colorants, flavorings, and solvents. These components can be mixed with water to prepare the composition. The amounts shown below are based on the total amount of the composition.

[0023] Examples of the abrasive include silica-based abrasives such as anhydrous silicic acid, silica gel, aluminosilicate, zirconosilicate, etc., calcium phosphate-based abrasives such as anhydrous or dihydrated calcium phosphate and tricalcium phosphate, calcium pyrophosphate, aluminum hydroxide, aluminum oxide, calcium carbonate, synthetic resin-based abrasives, etc. The amount of the abrasive to be blended is preferably 2 to 50%, particularly preferably 10 to 40%.

[0024] Examples of the thickening agent include sugar alcohols such as sorbitol, xylitol, erythritol, and reduced starch saccharification products, and polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol. The amount of the thickening agent is usually 5 to 50%.

[0025] Examples of the binder include alginic acid or its derivatives such as sodium alginate and propylene glycol alginate, gums such as xanthan gum, cellulose derivatives such as sodium carboxymethylcellulose and hydroxyethylcellulose, organic binders such as sodium polyacrylate, polyvinyl alcohol, and polyvinylpyrrolidone, and inorganic binders such as thickening silica. The amount of the binder is usually 0.1 to 10%.

[0026] As the optional surfactant, an anionic surfactant, a nonionic surfactant other than the component (B), a cationic surfactant, or an amphoteric surfactant can be blended. Examples of the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate, acyltaurates such as sodium lauroylmethyltaurate, acyl sarcosinates, and acyl amino acid salts. The amount of the anionic surfactant, particularly sodium lauryl sulfate, is preferably 0.001 to 10%, more preferably 0.01 to 5%, from the viewpoint of exerting the effects of the present invention. The nonionic surfactant may not be blended (0% blending amount) other than the component (B), but may be blended within a range that does not impair the effects of the present invention, in which case the blending amount is preferably 0.5% or less, more preferably 0.2% or less. Examples of the optional nonionic surfactant include sugar fatty acid esters, sugar alcohol fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, and polyoxyethylene higher alcohol ethers. Examples of cationic surfactants include alkyl ammonium types and quaternary ammonium salts such as alkylbenzyl ammonium salts, and examples of amphoteric surfactants include betaine types such as alkyl betaines and fatty acid amidopropyl betaines, and alkyl imidazole types such as 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolium betaines. The amount of the optional surfactant added is 0.01 to 10%, particularly 0.1 to 5%.

[0027] Examples of sweeteners include sodium saccharin, aspartame, stevioside, stevia extract, and paramethoxycinnamic aldehyde. Examples of the preservative include paraoxybenzoic acid esters such as methylparaben, ethylparaben, and butylparaben, and benzoic acid or a salt thereof. Colorants include Blue No. 1, Yellow No. 4, titanium dioxide, and the like.

[0028] 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, grapefruit oil, sweet ginger oil, Natural fragrances such as yuzu oil, iris concrete, absolute peppermint, absolute rose, orange flower, and processed fragrances (front distillation, back distillation, liquid-liquid extraction, essences, powdered fragrances, etc.) of these natural fragrances, as well as menthol, carvone, anethole, cineole, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linalyl acetate, limonene, Single flavors such as menthone, menthyl acetate, N-substituted-paramenthan-3-carboxamide, pinene, octylaldehyde, 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, as well as blended 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, and other known flavor materials used in oral compositions can be used in combination, and the flavors are not limited to those described in the examples. The amount of fragrance to be blended is not particularly limited, but the above-mentioned fragrance materials are preferably used in an amount of 0.000001 to 1% in the composition, and fragrances using the above-mentioned fragrance materials are preferably used in an amount of 0.1 to 2% in the composition.

[0029] The active ingredient may be any ingredient other than the (A) ingredient and the (C) ingredient, such as a nonionic bactericide, a cationic bactericide, an enzyme such as dextranase, a fluorine-containing compound such as sodium fluoride or sodium monofluorophosphate, a water-soluble phosphate compound, sodium chloride, potassium nitrate, aluminum lactate, a plant extract, an anti-tartar agent, or an anti-plaque agent. The amount of the active ingredient to be blended is an effective amount within a range that does not impair the effects of the present invention. EXAMPLES

[0030] The present invention will be described in detail below with reference to examples and comparative examples, but the present invention is not limited to the following examples. In the following examples, % indicates % by mass unless otherwise specified.

[0031] [Examples and Comparative Examples] Oral compositions (toothpastes) having the compositions shown in Tables 1 to 5 were prepared by conventional methods and evaluated by the following methods. The results are also shown in the tables. In the tables, the numbers in parentheses for polyoxyethylene hydrogenated castor oil are the average number of moles of ethylene oxide added.

[0032] (1) Method for evaluating the absorbability of allantoin or its derivatives A human three-dimensional epidermal model (LabCyte EPI-MODEL 24, manufactured by J-TEC Co., Ltd.) was cultured overnight in the attached medium. The cup in which the epidermal model was cultured was transferred to a 24-well plate to which PBS (phosphate buffered saline) was added, and 50 μL of a solution obtained by diluting the oral composition three-fold with artificial saliva was injected onto the surface of the epidermal model and allowed to stand for 3 minutes. After leaving the surface to stand, 50 μL of water was added to the surface of the epidermal model, and washing by pipetting was repeated twice. The washing solution was discarded, and 50 μL of water was added to the surface of the epidermal model. After culturing for 6 hours (37° C., 5% CO2), the epidermal model was removed and removed. Allantoin or its derivatives permeated into the PBS were quantified by absolute calibration curve method using HPLC under the following test conditions, and the amount absorbed into the epidermal model was determined. (Equipment used) Pump: Shimadzu Corporation LC-20AD Sample introduction unit: Shimadzu Corporation SIL-20AC Detector: Shimadzu Corporation SPD-20A Column thermostat: Shimadzu Corporation CTO-20AC ·Eluent flow rate: 1mL / min (Test conditions) Detector: UV spectrophotometer (measurement wavelength: 210 nm) Column: Inertsil NH2 (diameter 4.6 mm x length 250 mm, particle size 5 μm) Column temperature: 35℃ Eluent: Acetonitrile / phosphate buffer solution mixture (4:1) The absorption rate (%) was calculated assuming that the amount of allantoin or its derivative absorbed in the oral composition of Comparative Example 1 was 100%, and the absorbability of allantoin or its derivative (absorbability of component (A)) was determined from the obtained absorption rate using the following evaluation criteria to evaluate the absorbability into the oral mucosa. Evaluation criteria ◎:More than 150% ○: More than 100% and less than 150% ×: Less than 100%

[0033] (2) Evaluation method for usability (absence of bitterness) Nine subject monitors squeezed 1 g of oral composition packed in a standard laminated tube container out of the container, placed it on a toothbrush, and cleaned their mouths in the usual way. They then judged the taste (bitterness) using the following rating scale. Scoring criteria 4 points: No bitterness felt 3 points: Almost no bitterness 2 points: Bitter taste but tolerable 1: Unacceptably bitter The scores of the nine panelists were averaged, and the feel in use (absence of bitterness) was evaluated according to the following criteria. Evaluation criteria: ◎: 3.5 points or more ○: 3.0 points or more and less than 3.5 points ●: 2.0 points or more and less than 3.0 points ×: Less than 2.0 points

[0034] (3) Method for evaluating the storage stability of allantoin or its derivatives over time The oral composition filled in a general laminated tube container was stored for 2 weeks in a thermostatic chamber at 50° C. or -5° C. After leaving it to reach room temperature, 1.5 g of the oral composition was extruded from the container and separated, 20 mL of 80% ethanol was added, the mixture was shaken for 15 minutes, and centrifuged (3,000 rpm, 10 minutes). Allantoin or its derivatives in the supernatant were quantified by HPLC using the absolute calibration curve method under the following test conditions, and the contents of allantoin or its derivatives in the samples stored at 50° C. and -5° C. were calculated. (Equipment used) Pump: Shimadzu Corporation LC-20AD Sample introduction unit: Shimadzu Corporation SIL-20AC Detector: Shimadzu Corporation SPD-20A Column thermostat: Shimadzu Corporation CTO-20AC ·Eluent flow rate: 1mL / min (Test conditions) Detector: UV spectrophotometer (measurement wavelength: 273 nm) Column: Inertsil NH2 (diameter 4.6 mm x length 250 mm, particle size 5 μm) Column temperature: 35℃ Eluent: Acetonitrile / phosphate buffer solution mixture (4:1) The residual rate (%) of allantoin or its derivatives was calculated from the content of the product stored at 50°C when the content of allantoin or its derivatives in the product stored at -5°C was taken as 100%, and the storage stability over time of allantoin or its derivatives (storage stability of component (A)) was evaluated according to the following evaluation criteria. Evaluation criteria ◎: Remaining rate of allantoin or its derivatives is 95% or more ○: The remaining rate of allantoin or its derivatives is 90% or more but less than 95%. ×: The remaining rate of allantoin or its derivatives is less than 90%.

[0035] [Table 1]

[0036] [Table 2]

[0037] [Table 3]

[0038] [Table 4]

[0039] [Table 5] *: In Comparative Example 1, which did not contain the component (B), no bitterness was observed.

Claims

1. (A) allantoin or a derivative thereof, (B) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 5 to 10 moles, and (C) Vitamin E or its derivatives The composition comprises An oral composition having a mass ratio of (A) / (B) of 0.01 to 5 and a mass ratio of (A) / (C) of 0.03 to 2, a content of component (A) of 0.01 to 0.2 mass%, and a pH of the composition at 25°C of 4 to 6.

4.

2. 2. The oral composition according to claim 1, wherein the mass ratio of (A) / (B) is 0.05 to 5.

3. 3. The oral composition according to claim 1, wherein the mass ratio of (B) / (C) is 0.2 to 60.

4. The oral composition according to any one of claims 1 to 3, wherein the content of component (B) is 0.1 to 3 mass %, and the content of component (C) is 0.01 to 3 mass %.

5. The oral composition according to any one of claims 1 to 4, which is a dentifrice composition.

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