Oral composition

Abstract

To provide an oral composition usable for applications including tissue repair of gingiva.SOLUTION: An oral composition for application to the oral cavity including gingiva is prepared that comprises (A) 0.35 to 0.55 mass% of an allantoin and (B) 0.3 to 0.45 mass% of a glycyrrhetinic acid. Furthermore, a collagen production promoter is prepared that comprises an allantoin and a glycyrrhetinic acid.SELECTED DRAWING: None

Description

[Technical Field]

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

[0002] Periodontal disease (also known as periodontal pathology) refers to the impairment of the health of periodontal tissues, including conditions such as pyorrhea and gingivitis. Periodontal tissues consist of the gingiva (gums), alveolar bone (the bone tissue that supports the teeth), cementum covering the tooth roots, and the periodontal ligament connecting the tooth roots to the alveolar bone. These structures provide a robust foundation for firmly attaching and securing teeth in their proper positions. However, when bacteria colonize the spaces between the teeth and gums and dental plaque accumulates, health conditions are compromised, resulting in loose teeth, bad breath, and a decline in quality of life. The risk of periodontal disease increases with age-related deterioration of the oral environment, such as a decrease in saliva, as well as lifestyle habits, aging, and diseases such as diabetes. It is also known that periodontal disease affects immune cells, exacerbating diabetes and cardiovascular disease. The prevalence of periodontal disease is on the rise in aging societies, and the development of effective treatment and prevention methods for periodontal disease is an important challenge for maintaining and promoting public health and reducing medical costs.

[0003] For advanced periodontal disease, surgical treatment has been used to remove dental plaque, tartar, and other debris from the affected area to improve the condition. Meanwhile, chemical approaches have also been used to improve periodontal disease, either in combination with surgical treatment or alone. Periodontal disease progresses deep into the gums, but chemical approaches offer an advantage over surgical treatment in that they can be effective from the gap between the teeth and gums all the way to the back of the mouth. Among these chemical approaches, methods that have been reported so far include suppressing or reducing the bacteria that cause inflammation with antibacterial agents or disinfectants (Patent Document 1), and applying periodontal tissue regeneration-promoting substances to the affected area to promote regeneration (Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2016-113460 [Patent Document 2] Japanese Patent Application Publication No. 2017-12188 Summary of the Invention [Problem to be solved by the invention]

[0005] While these chemical approaches are effective for periodontal tissue repair and prevention, they require continuous oral administration, which can often result in a bitter or unpleasant taste when the drug comes into contact with the tongue. Bitter or unpleasant tastes can make oral administration and continued use difficult. Therefore, taste control is an important issue for oral administration.

[0006] The present invention has been made in view of the above, and aims to provide an oral composition that has an excellent feel when used, including a good taste when applied. [Means for solving the problem]

[0007] In view of the above-mentioned problems, the present inventors have conducted extensive research and have found that by combining specific concentrations of allantoins and glycyrrhizic acids, a composition suitable for application to the oral cavity, such as the gums, can be obtained, thereby completing one aspect of the present invention.

[0008] Furthermore, the present inventors have discovered that the collagen production promoting effect is enhanced by combining allantoins with glycyrrhizic acids, and have thus completed another aspect of the present invention.

[0009] That is, the present invention provides the oral compositions described below. Section 1. (A) 0.35 to 0.55% by mass of allantoins, and (B) 0.3 to 0.45% by mass of glycyrrhizinic acids An oral composition comprising: Section 2. Item 1. The oral composition according to Item 1, further comprising cetylpyridinium or a salt thereof. Section 3. Item 3. The oral composition according to Item 1 or 2, further comprising menthol and / or hinokitiol. Section 4. Item 4. The oral composition according to any one of Items 1 to 3, further comprising a hydrocarbon. Section 5. Item 5. The oral composition according to any one of Items 1 to 4, which is in the form of an ointment. Section 6. Item 6. The oral composition according to any one of Items 1 to 5, which is used for treating or preventing periodontal disease. Section 7. A method for imparting to an oral composition the effect of reducing discomfort upon application by incorporating (A) 0.35 to 0.55 mass% of an allantoin and (B) 0.3 to 0.45 mass% of a glycyrrhizinic acid. Section 8. A collagen production promoter for fibroblasts containing allantoins and glycyrrhizic acids. Section 9. A method for imparting to a composition the effect of promoting collagen production by fibroblasts by allowing an allantoin compound and a glycyrrhizinic acid compound to coexist in the composition. [Effects of the Invention]

[0010] According to the present invention, an oral composition can be provided that can treat, prevent, or improve symptoms such as oral diseases and inflammation, and that has an excellent feel when used. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a graph comparing the amount of collagen produced by samples from an example of the present invention and a reference example with that of a reference example. DETAILED DESCRIPTION OF THE INVENTION

[0012] As used herein, "pharmaceutically acceptable salts" or "salts" include, but are not limited to, salts with alkali metals, alkaline earth metals, organic bases, etc., including salts with sodium, potassium, calcium, magnesium, ammonium, or diethanolamine, ethylenediamine, etc. Further examples include salts with amines such as ammonia, methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris(hydroxymethyl)aminomethane, N,N-bis(hydroxyethyl)piperazine, 2-amino-2-methyl-1-propanol, ethanolamine, N-methylglucamine, L-glucamine, etc., or salts with basic amino acids such as lysine, δ-hydroxylysine, arginine, etc. Other examples include salts with mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid; salts with organic acids such as methanesulfonic acid, benzenesulfonic acid, paratoluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, malic acid, oxalic acid, succinic acid, valeric acid, citric acid, benzoic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid, and salicylic acid; and salts with acidic amino acids such as aspartic acid and glutamic acid. "Pharmaceutically acceptable salt" or "salt" may include solvates or hydrates of the salt.

[0013] [Oral composition] One aspect of the present invention is a method for producing a medicament for the treatment of a pulmonary arthritis. (A) 0.35 to 0.55% by mass of allantoins; and (B) The present invention relates to an oral composition containing 0.3 to 0.45% by mass of glycyrrhizinic acids and intended for application to the gums and other areas of the oral cavity.

[0014] ((A) Allantoin) The allantoin included in the embodiment of the present invention is one of anti-inflammatory agents, and is not particularly limited as long as it is of the grade used in pharmaceuticals, quasi-drugs, cosmetics, and the like.

[0015] Examples of allantoins include allantoin, allantoin derivatives, and pharmacologically acceptable salts thereof, specifically allantoin, allantoin β-glycyrrhetinic acid, allantoin dihydroxyaluminum (aldioxa), allantoin chlorohydroxyaluminum (alcloxa), allantoin polygalacturonic acid, allantoin ascorbic acid, allantoin acetyl-DL-methionine, allantoin DL-pantothenyl alcohol, and sodium DL-pyrrolidonecarboxylate·allantoin. Among these, from the viewpoint of the common basic skeleton of their chemical structures, preferred are allantoin, allantoin dihydroxyaluminum (aldioxa), and allantoin chlorohydroxyaluminum (alcloxa), more preferred are allantoin and allantoin chlorohydroxyaluminum (alcloxa), and particularly preferred is allantoin.

[0016] The oral composition of this embodiment contains 0.35 to 0.55% by mass of (A) allantoins. The content of allantoins in the oral composition is 0.35% by mass or more, preferably 0.4% by mass or more, more preferably 0.45% by mass or more, and even more preferably 0.5% by mass or more. The content of allantoins in the oral composition is preferably 0.55% by mass or less, more preferably 0.5% by mass or less. Most preferably, allantoin is 0.5% by mass.

[0017] ((B) Glycyrrhizic acid) The glycyrrhizic acid included in the embodiment of the present invention is one of anti-inflammatory agents, and is not particularly limited as long as it is of the grade used in pharmaceuticals, quasi-drugs, cosmetics, and the like.

[0018] The glycyrrhizinic acid derivatives include glycyrrhizinic acid, derivatives of glycyrrhizinic acid, and pharmacologically acceptable salts thereof, and specific examples thereof include glycyrrhizinic acid, glycyrrhetinic acid, dipotassium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, monoammonium glycyrrhizinate, glycerin glycyrrhetinate, stearyl glycyrrhetinate, etc. Among these, dipotassium glycyrrhizinate is preferred, although not limited thereto.

[0019] The oral composition of this embodiment contains 0.3 to 0.45% by mass of (B) glycyrrhizic acids. The content of glycyrrhizic acids in the oral composition is preferably 0.3% by mass or more, more preferably 0.35% by mass or more, and more preferably 0.4% by mass or more. The content of glycyrrhizic acids in the oral composition is preferably 0.45% by mass or less, more preferably 0.4% by mass or less. The content of glycyrrhizic acids is most preferably 0.4% by mass.

[0020] In the oral composition of this embodiment, the ratio of the content of component (A) to component (B) is, from the viewpoint of enhancing the effects of the present invention, preferably 0.7 to 1.9 parts by mass of component (A) per 1 part by mass of component (B), more preferably 0.78 to 1.8 parts by mass, even more preferably 0.8 to 1.7 parts by mass, even more preferably 0.9 to 1.5 parts by mass, even more preferably 1 to 1.3 parts by mass, particularly preferably 1.2 to 1.3 parts by mass, and most preferably 1.25 parts by mass.

[0021] (cetylpyridinium or its salts) The oral composition of this embodiment may contain cetylpyridinium or a salt thereof in addition to components (A) and (B), as long as the effects of the present invention are not impaired. Cetylpyridinium or a salt thereof may include, but is not limited to, chloride hydrate. The cetylpyridinium or a salt thereof used in this embodiment is not particularly limited as long as it is of the same grade as that used in pharmaceuticals, quasi-drugs, cosmetics, etc. The content of cetylpyridinium or a salt thereof in the oral composition is not limited, but may be, for example, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, or 0.05% by mass or more. The content of cetylpyridinium or a salt thereof in the oral composition is not limited, but may be, for example, 0.3% by mass or less, less than 0.3% by mass, 0.25% by mass or less, 0.2% by mass or less, 0.15% by mass or less, or 0.1% by mass or less, with 0.05% by mass or less being preferred. The content of cetylpyridinium chloride hydrate is particularly preferably 0.05% by mass.

[0022] In the oral composition of this embodiment, from the viewpoint of enhancing the effects of the present invention, the ratio of the content of cetylpyridinium or a salt thereof to component (A) is preferably 0.001 to 1 part by mass, more preferably 0.01 to 0.6 parts by mass, even more preferably 0.03 to 0.5 parts by mass, even more preferably 0.05 to 0.3 parts by mass, particularly preferably 0.08 to 0.15 parts by mass, and most preferably 0.1 part by mass, of cetylpyridinium or a salt thereof per 1 part by mass of component (A).

[0023] (menthol) The oral composition of this embodiment may contain menthol in addition to the components (A) and (B), as long as the effects of the present invention are not impaired. The menthol used in this embodiment is not particularly limited, as long as it is of the same grade as that used in pharmaceuticals, quasi-drugs, cosmetics, etc. Both natural and synthetic menthols can be used, and any of the d-, l-, or dl-isomers may be used. As menthol, l-menthol is particularly preferred. Essential oils containing menthol can also be used. Examples of such essential oils include peppermint oil, cool mint oil, spearmint oil, and peppermint oil. Peppermint oil is preferred as the essential oil, and peppermint oil refers to oil containing 30% or more menthol, for example (as described in the Japanese Pharmacopoeia). The content of menthol in the oral composition is not limited, but may preferably be 0.0001% by mass or more, 0.001% by mass or more, 0.005% by mass or more, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.3% by mass or more, or 0.5% by mass or more, and may be 2% by mass or less, 1.5% by mass or less, or 1% by mass or less.

[0024] (Hinokitiol) The oral composition of this embodiment may contain hinokitiol in addition to components (A) and (B), as long as the effects of the present invention are not impaired. The hinokitiol used in this embodiment is not particularly limited, as long as it is of the same grade as that used in pharmaceuticals, quasi-drugs, cosmetics, etc. The content of hinokitiol in the oral composition is not limited, but is preferably 0.01% by mass or more, 0.03% by mass or more, 0.05% by mass or more, or 0.1% by mass or more, and 2% by mass or less, 1% by mass or less, 0.5% by mass or less, 0.3% by mass or less, 0.2% by mass or less, or 0.1% by mass or less. 0.1% by mass is the most preferred.

[0025] In the oral composition of this embodiment, the ratio of the content of hinokitiol to component (A) is, from the viewpoint of enhancing the effects of the present invention, preferably 0.01 to 5 parts by mass, more preferably 0.05 to 2 parts by mass, even more preferably 0.1 to 1 part by mass, even more preferably 0.15 to 0.5 parts by mass, particularly preferably 0.15 to 0.3 parts by mass, and most preferably 0.2 parts by mass, per 1 part by mass of component (A).

[0026] (hydrocarbons) The oral composition of this embodiment may contain a hydrocarbon in addition to components (A) and (B), as long as the hydrocarbon does not impair the effects of the present invention. The hydrocarbon used in this embodiment is not particularly limited as long as it is of the same grade as that used in pharmaceuticals, quasi-drugs, cosmetics, etc. By including a hydrocarbon, the effects of the present invention are more pronounced.

[0027] As the hydrocarbon, a paraffinic hydrocarbon or an olefinic hydrocarbon is used, and examples thereof include liquid paraffin, petrolatum, gelled hydrocarbon, squalane, squalene, ceresin, light liquid paraffin, paraffin wax, beeswax, white beeswax, carnauba wax, pristane, microcrystalline wax, etc. From the viewpoint of further enhancing the effects of the present invention, liquid paraffin, petrolatum, white beeswax, and microcrystalline wax are more preferred, and one type may be used alone, or two or more types may be used in combination.

[0028] The total content of hydrocarbons is not particularly limited and is set appropriately depending on the type of hydrocarbon, the type and content of other blended ingredients, the formulation, the method of use, etc. The total content of hydrocarbons in the oral composition is preferably 10% by mass or more, 20% by mass or more, 30% by mass or more, 40% by mass or more, 50% by mass or more, 60% by mass or more, 65% by mass or more, 70% by mass or more, or 75% by mass or more, and can be 95% by mass or less, 90% by mass or less, or 85% by mass or less.

[0029] Of the hydrocarbons, for example, petrolatum can be 1% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, or 35% by mass or more, and can be 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, or 40% by mass or less.

[0030] Of the hydrocarbons, for example, liquid paraffin can be 1% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 25% by mass or more, 30% by mass or more, or 35% by mass or more, and can be 90% by mass or less, 80% by mass or less, 70% by mass or less, 60% by mass or less, 50% by mass or less, or 40% by mass or less.

[0031] In the oral composition of this embodiment, the ratio of the content of petrolatum to 1 part by mass of liquid paraffin can be 0.001 parts by mass or more, 0.01 parts by mass or more, 0.1 parts by mass or more, 0.5 parts by mass or more, or 1 part by mass or more, and can be 1000 parts by mass or less, 100 parts by mass or less, 10 parts by mass or less, or 5 parts by mass or less.

[0032] (vitamin supplement) The oral composition of this embodiment may contain a vitamin preparation in addition to the components (A) and (B), as long as the effects of the present invention are not impaired. The vitamin preparation used in this embodiment is not particularly limited as long as it is of the same grade as that used in pharmaceuticals, quasi-drugs, cosmetics, etc. By including a vitamin preparation, the effects of the present invention are more pronounced.

[0033] Vitamin preparations include, for example, vitamin A oil, retinol palmitate, retinol acetate, ascorbic acid, sodium ascorbate, calcium ascorbate, tocopherol, tocopherol acetate, tocopherol succinate, tocopherol calcium succinate, tocopherol nicotinate, panthenol, sodium pantothenate, calcium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate, vitamin B2, riboflavin, riboflavin sodium phosphate, riboflavin butyrate, Examples include flavin adenine dinucleotide sodium, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, hydroxocobalamin, nicotinamide, biotin, thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate, dicethiamine hydrochloride, fursultiamine hydrochloride, octotiamine, shikotiamine, bis-ibutiamine, bis-bentiamine, fursultiamine, prosultiamine, and / or benfotiamine. Of these, tocopherol acetate is preferred, but is not limited to.

[0034] (Medicinal or refreshing ingredients) The oral composition of the present invention may contain medicinal ingredients and / or cooling ingredients in addition to components (A) and (B), as long as the effects of the present invention are not impaired. Such ingredients include camphor, geraniol, cineole, borneol, limonene, rhubarb, fennel oil, cinnamon oil, bergamot oil, eucalyptus oil, rose oil, carbazochrome, callopeptide, potassium nitrate, and / or palatinit. Although not limited thereto, carbazochrome is preferred as the medicinal ingredient.

[0035] (thickener) The oral composition of this embodiment may contain a thickener in addition to components (A) and (B), as long as the effects of the present invention are not impaired. The thickener can enhance the adhesion of the oral composition to the mouth. Examples of thickeners include, but are not limited to, cellulose-based polymers, vinyl-based polymers, acrylic polymers, mucopolysaccharides, starch-based polymers, dextran, dextrin fatty acid esters, pectin, casein, dimethyldistearylammonium hectorite, (acryloyldimethyltaurate ammonium / vinylpyrrolidone) copolymer, polyethylene glycol distearate, ethylene glycol triisostearate, polyoxyethylene(20)methylglucoside triisostearate, bentonite, hectorite, alginic acid and / or a salt thereof. Among these, cellulose-based polymers and / or vinyl-based polymers are particularly preferred.

[0036] Examples of the cellulose-based polymer include sodium carboxymethylcellulose (carmellose sodium), methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose.

[0037] Examples of vinyl polymers include carboxyvinyl polymer, polyvinylpyrrolidone, polyvinyl alcohol, and polyvinyl methyl ether.

[0038] These thickeners may be used alone or in combination of two or more.

[0039] Among these, sodium carboxymethylcellulose (carmellose sodium) and / or carboxyvinyl polymer are preferred, although not limited thereto, from the viewpoint of achieving the effects of the present invention.

[0040] The total content of the thickener is not particularly limited, and can be 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 0.3% by mass or more, 0.5% by mass or more, 1% by mass or more, 1.5% by mass or more, 2% by mass or more, or 5% by mass or more, and can be 20% by mass or less, 15% by mass or less, or 10% by mass or less.

[0041] For example, the content of the cellulose-based polymer is not particularly limited, and can be 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 0.3% by mass or more, 0.5% by mass or more, 1% by mass or more, 1.5% by mass or more, or 2% by mass or more, and can be 20% by mass or less, 15% by mass or less, 10% by mass or less, or 5% by mass or less.

[0042] For example, the content of the vinyl polymer is not particularly limited, and can be 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 0.3% by mass or more, 0.5% by mass or more, 1% by mass or more, 1.5% by mass or more, or 2% by mass or more, and can be 20% by mass or less, 15% by mass or less, 10% by mass or less, or 5% by mass or less.

[0043] (Additives) The oral composition of this embodiment can contain various other additives as long as they do not impair the effects of the present invention. Examples of such additives include those listed in the "Dictionary of Pharmaceutical Additives 2021 (edited by the Japan Pharmaceutical Additives Association)."

[0044] Examples of additives include light anhydrous silicic acid, anhydrous silicic acid, pH adjusters, antioxidants, chelating agents, oils, colorants, fragrances, wetting agents, surfactants, and solvents.

[0045] (Dosage form) The oral composition of this embodiment is not particularly limited as long as it is in a form known as a pharmaceutical, quasi-drug, or cosmetic, and can be formulated by a known method, for example, in the form of an ointment, gel, dentifrice, cream, liquid, etc. From the viewpoint of more significantly exhibiting the effects of the present application, cream, gel, and ointment are preferred, and ointment is more preferred. By formulating it in such a form, it can be made into a form suitable for application to the gums, for example, and can fully exhibit its effects.

[0046] When the oral composition is formulated in a semi-solid or solid form such as a cream, ointment, gel, or dentifrice, it can be placed in a tube container, although this is not a limitation. This allows the optimal amount of the oral composition of the present invention to be squeezed out and makes it easier to apply directly to the affected area with fingers or the like. Examples of materials for the tube container include aluminum and aluminum laminate. The viscosity can also be adjusted to allow application to a narrow or wide area of ​​the affected area. After applying the oral composition of the present invention to the affected area, it can also be used by spreading it out by massaging with the fingers.

[0047] Examples of application sites of the oral composition of this embodiment include the gums, the inside of the cheeks, the inside of the lips, etc. In particular, the gums include not only the areas around the teeth but also the bases of the teeth and their vicinity.

[0048] The effective dose of the oral composition of this embodiment can be appropriately determined depending on the application and formulation, but is about 0.2 to 0.5 g per dose, and is applied several times a day, preferably 2 to 4 times a day.

[0049] Applying the oral composition of this embodiment to the oral cavity, such as to the gums, improves periodontal diseases such as pyorrhea, which can lead to tooth loss, and the precursor symptoms leading to such diseases. The oral composition of this embodiment makes it possible to prevent periodontal disease, repair gums, or treat or prevent stomatitis. That is, the oral composition of the present invention can be used for periodontal tissue regeneration, promotion of periodontal tissue repair, gingival cell activation, promotion of gingival cell repair, periodontal disease prevention, periodontal disease treatment, prevention of pyorrhea, and / or treatment of pyorrhea, or for the treatment or prevention of stomatitis.

[0050] (Manufacturing method) The oral composition of this embodiment can be produced by a known method, which may include a sterilization step, if necessary.

[0051] [Method for reducing discomfort when applying an oral composition] Another aspect of the present invention relates to a method for imparting the effect of reducing discomfort upon application to an oral composition by incorporating (A) 0.35 to 0.55% by mass of an allantoin and (B) 0.3 to 0.45% by mass of a glycyrrhizinic acid. Here, "reducing discomfort" specifically refers to reducing the unpleasant taste and aftertaste caused by the medicine touching the tongue when applied to the mouth. Examples of unpleasant tastes include oily odor, bitterness, lack of refreshing feeling, and / or slow sweetness. By reducing these, the composition provides a comfortable application and a good usability.

[0052] In the method for imparting the effect of reducing discomfort upon application to an oral composition, the content of allantoins is 0.35% by mass or more, preferably 0.4% by mass or more, more preferably 0.45% by mass or more, or 0.5% by mass or more, and 0.55% by mass or less, and most preferably 0.5% by mass.

[0053] In the method for imparting the effect of reducing discomfort during application to an oral composition, the content of glycyrrhizic acids is 0.3% by mass or more, preferably 0.35% by mass or more, more preferably 0.4% by mass or more, and preferably 0.45% by mass or less, more preferably 0.4% by mass or less, and most preferably 0.4% by mass.

[0054] [Collagen production promoter] Another aspect of the present invention relates to a collagen production promoter containing (A) an allantoin and (B) a glycyrrhizinic acid. The collagen production promoter of this aspect can promote collagen production in cells and tissues in the oral cavity, but is not limited thereto. The type of cells and tissues may be, but is not limited to, periodontal ligament fibroblasts or tissues containing such cells, for example.

[0055] The content of allantoins in the collagen production promoter is not limited, but is preferably 0.001% by mass or more, 0.1% by mass or more, 0.2% by mass or more, 0.3% by mass or more, 0.35% by mass or more, 0.4% by mass or more, or 0.45% by mass or more, and 2% by mass or less, 1.5% by mass or less, 1% by mass or less, or 0.55% by mass or less, and most preferably 0.5% by mass.

[0056] The content of glycyrrhizic acids in the collagen production promoter is not limited, but can be preferably 0.001% by mass or more, 0.1% by mass or more, 0.2% by mass or more, 0.3% by mass or more, or 0.35% by mass or more, and can be 2% by mass or less, 1.5% by mass or less, 1% by mass or less, 0.5% by mass or less, or 0.45% by mass or less, and most preferably 0.4% by mass.

[0057] Other conditions in this method can be in accordance with the conditions disclosed in [Oral Composition].

[0058] [Method for imparting collagen production promoting effect] Another aspect of the present invention relates to a method for imparting an effect of promoting collagen production by fibroblasts by allowing glycyrrhizinic acids and allantoins to coexist in a composition.

[0059] The content of allantoin salts in the method for enhancing collagen production ability is not limited, but when contained in the oral composition, it is preferably 0.35% by mass or more, more preferably 0.4% by mass or more, even more preferably 0.45% by mass or more, or 0.5% by mass or more, and preferably 0.55% by mass or less, and most preferably 0.5% by mass.

[0060] The content of glycyrrhizinic acids in the method for enhancing collagen production ability is not limited, but when contained in an oral composition, it is preferably 0.3% by mass or more, 0.35% by mass or more, preferably 0.45% by mass or less, and most preferably 0.4% by mass.

[0061] Other conditions in this method can be in accordance with the conditions disclosed in [Oral Composition]. [Example]

[0062] Next, the present invention will be specifically explained by way of examples, but the present invention is not limited to the following examples.

[0063] The compositions of the Examples and Reference Examples shown in Table 1 were prepared according to a conventional method for preparing ointments.

[0064] [Test Example 1: Sensory Evaluation Test] Sensory evaluation was performed using the compositions of the standard example, examples, and reference examples shown in Table 1. Five panelists were selected for the sensory evaluation, and they were all experts in the development or evaluation of oral compositions. To standardize the evaluation criteria among the panelists, a formulation containing no active ingredient (standard example 1-1) was used to align their understanding of each evaluation item. The evaluation method involved taking a fingernail-sized portion of each test sample (compositions of the examples and reference examples) on a spoon and placing it on the tongue for evaluation.

[0065] The evaluation items were oily smell, sweetness, refreshing feeling, immediate unpleasant sensation, rapidity of sweetness fading, bitterness when drinking water after ingestion, and unpleasant aftertaste when drinking water after ingestion. The higher the scores for oily smell, sweetness, immediate unpleasant sensation, bitterness, and unpleasant aftertaste, the less sensitive each item was to the sensory sensation, while the higher the scores for refreshing feeling and rapidity of sweetness fading, the stronger each item was to the sensory sensation. The analysis method used was to convert the VAS line to 10 cm, measure the distance from the left individually, and calculate the average value for all panelists.

[0066] Before the evaluation, panelists adjusted their evaluation of the standard composition to match the center of the VAS evaluation, and then evaluated each item in comparison with the standard. To ensure more accurate evaluation, participants drank water when switching compositions and waited at least three minutes.

[0067] [Table 1]

[0068] The results are shown in Table 2. [Table 2] As described above, it was found that the compositions of the Examples had a less oily smell than the compositions of the Reference Examples, a refreshing feeling, less unpleasant sensation immediately after ingestion, less bitterness when drinking water after ingestion, and less unpleasant aftertaste when drinking water after ingestion. The sweetness and the rapidity of the sweetness decay were also within the preferred ranges for the compositions of the Examples, and the unpleasant sensation was suppressed more than that of the Reference Examples.

[0069] [Test Example 2: Type I collagen gene expression verification test] As shown in Table 3 below, human periodontal ligament fibroblasts (HPLF) were used, and various concentrations of allantoin and / or dipotassium glycyrrhizinate were added to cells that were induced to mimic periodontal disease by inducing inflammation. Test samples for the Examples and Reference Examples were then prepared, and the RNA expression level of COL1A1 (type I collagen gene) was examined after 72 hours of culture.

[0070] To obtain these data, HPLF cells were seeded in DMEM medium (Gibco, 10% FBS) on day 1. The medium was replaced with DMEM medium (0.1% FBS) on day 2. On day 3, the medium was replaced with DMEM medium (0.1% FBS) supplemented with 0.4% by mass of dipotassium glycyrrhizinate (Reference Example 2-1) or 0.4% by mass of dipotassium glycyrrhizinate and 0.5% by mass of allantoin (Example 2-2). Subsequently, inflammation was induced with LPS. For the control (Reference Example 2-1), inflammation was induced by LPS stimulation without adding any sample. After 72 hours of LPS stimulation, RNA was collected, and the amount of COL1A1 RNA was quantified by PCR. The amount of COL1A1 RNA was quantified using the ΔΔCt method, with the GAPDH gene as a normalizer. Figure 1 shows the relative expression levels, with the control (Reference Example 2-1) set to 100.

[0071] [Table 3]

[0072] In Reference Example 2-1, which contained 0.4% dipotassium glycyrrhizinate, the expression level of the collagen gene increased compared to the control (Reference Example 2-1), to which nothing was added, and in Example 2-2, to which allantoin was added, the expression level of the collagen gene also increased significantly (*: p<0.05, **: p<0.01).

[0073] Formulation examples of the oral compositions of the present invention are shown below. Note that all of the formulation examples in Formulation Example 1 and Table 4 are ointments.

[0074] (Formulation Example 1) Allantoin 0.5g, tocopherol acetate 2g, dipotassium glycyrrhizinate 0.4g, carbazochrome 0.02g, hinokitiol 0.1g, cetylpyridinium chloride hydrate 0.05g, petrolatum, liquid paraffin, paraffin, anhydrous silicic acid, white beeswax, microcrystalline wax, carboxyvinyl polymer, carmellose sodium, polyethylene, sorbitan monostearate, dibutylhydroxytoluene, pectin, peppermint oil, fennel oil, l-menthol, thymol, sodium edetate, fragrance, Red No. 3 (per 100g)

[0075] [Table 4]

Claims

1. (A) 0.35 to 0.55% by mass of allantoins, and (B) 0.3 to 0.45% by mass of glycyrrhizic acids An oral composition comprising:

2. The oral composition according to claim 1 , further comprising cetylpyridinium or a salt thereof.

3. The oral composition according to claim 1 or 2, further comprising menthol and / or hinokitiol.

4. The oral composition according to claim 1 or 2, further comprising a hydrocarbon.

5. The oral composition according to claim 1 or 2, which is in the form of an ointment.

6. The oral composition according to claim 1 or 2, which is used for the treatment or prevention of periodontal disease.

7. A method for imparting to an oral composition the effect of reducing discomfort upon application by incorporating (A) 0.35 to 0.55% by mass of an allantoin and (B) 0.3 to 0.45% by mass of a glycyrrhizinic acid.

8. A collagen production promoter for fibroblasts containing allantoins and glycyrrhizic acids.

9. A method for imparting to a composition the effect of promoting collagen production by fibroblasts by allowing an allantoin compound and a glycyrrhizinic acid compound to coexist in the composition.

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