Stomatitis onset-suppressing composition

Abstract

To provide a stomatitis onset-suppressing composition for suppressing the onset of stomatitis.SOLUTION: The present invention provides a stomatitis onset-suppressing composition comprising at least one selected from (A) glycyrrhizic acid and (B) tranexamic acid as active ingredients, and (C) an extract of Equisetum arvense.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition for suppressing the onset of stomatitis that suppresses (prevents) the onset of stomatitis. [Background technology]

[0002] Stomatitis is a general term for inflammation occurring in the oral mucosa, and is classified into catarrhal stomatitis, aphthous stomatitis, drug-induced stomatitis, radiation stomatitis, etc., depending on the cause. Catarrhal stomatitis is stomatitis that develops due to physical stimuli such as contact with dentures or orthodontic appliances, malocclusion, etc. Aphthous stomatitis is stomatitis that develops mainly due to psychological stress, but the mechanism of its development is unknown. Drug-induced stomatitis is stomatitis induced by anticancer drugs, etc., and is a severe, intractable stomatitis that is accompanied by strong pain and spreads over a wide area. Radiation stomatitis is stomatitis that develops mainly due to radiation used in the treatment of oral cancer, pharyngeal cancer, etc.

[0003] One of the main symptoms of stomatitis is severe contact pain, which can cause difficulty in eating, swallowing, speaking, brushing the teeth, etc., and is therefore a major problem.

[0004] Conventionally, oral preparations containing tissue repair agents and anti-inflammatory agents have been used for stomatitis, and ointments, patches, sprays, etc. have been applied directly to stomatitis, or oral medications have been used to treat stomatitis from within the body. For example, Patent Document 1 proposes an oral composition containing allantoin or its derivatives and vitamin B5 or its derivatives. It has been shown that the oral composition of Patent Document 1 has an oral wound healing effect and is effective in treating stomatitis. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2007-8831 A Summary of the Invention [Problem to be solved by the invention]

[0006] Thus, until now, symptomatic treatment has been performed for stomatitis after the onset, but there is a demand for suppressing the onset of stomatitis itself. Therefore, an object of the present invention is to provide a composition for suppressing the onset of stomatitis for suppressing the onset of stomatitis. [Means for solving the problem]

[0007] As a result of extensive research, the inventors have discovered that continuous application of a composition containing at least one of glycyrrhizinic acid (ingredient (A)) and tranexamic acid (ingredient (B)) to the oral cavity has the effect of suppressing the onset of stomatitis, and that this efficacy is enhanced by the addition of an extract of horsetail (ingredient (C)), thereby completing the present invention.

[0008] That is, the present invention is achieved by the following (1) and (2). (1) A composition for suppressing the onset of stomatitis, comprising as active ingredients at least one of (A) glycyrrhizinic acid and (B) tranexamic acid, and (C) an extract of horsetail. (2) (C) An agent for enhancing the efficacy of suppressing the onset of stomatitis, which contains an extract of horsetail (A) and at least one of glycyrrhizinic acid and (B) tranexamic acid as an active ingredient. Effect of the Invention

[0009] The composition for suppressing the onset of stomatitis of the present invention contains at least one of glycyrrhizinic acid (component (A)) and tranexamic acid (component (B)) and an extract of horsetail (component (C)), and thus has an excellent effect of suppressing the onset of stomatitis. In addition, the effect of suppressing the onset of stomatitis can be obtained by at least one of glycyrrhizinic acid (component (A)) and tranexamic acid (component (B)). In addition, the effect of suppressing the onset of stomatitis can be enhanced by using a stomatitis onset suppression efficacy enhancer containing an extract of horsetail (component (C)) as an active ingredient in combination with at least one of glycyrrhizinic acid (component (A)) and tranexamic acid (component (B)). In this way, a composition for suppressing the onset of stomatitis having an excellent effect of suppressing the onset of stomatitis can be obtained. The risk of developing stomatitis can be reduced by continuously applying the composition for suppressing the onset of stomatitis of the present invention to the oral cavity. In addition, a composition for suppressing the onset of stomatitis that can be used easily and safely can be provided. The composition for suppressing the onset of stomatitis of the present invention is suitable for use as a liquid dentifrice, a mouthwash (gargle), a mouthwash, or a mouth spray. [Brief description of the drawings]

[0010] [Figure 1] 1 is a graph showing the evaluation results of the effect of suppressing the onset of stomatitis in Test Example 1. [Diagram 2] 1 is a graph showing the evaluation results of the effect of suppressing the onset of stomatitis in Test Example 2. [Diagram 3] 1 is a graph showing the evaluation results of the stomatitis healing effect in Test Example 3. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] Hereinafter, the embodiments of the present invention will be described in more detail.

[0012] (Composition for inhibiting the onset of stomatitis) The composition for suppressing the onset of stomatitis of the present invention contains at least one of glycyrrhizinic acid (component (A)) and tranexamic acid (component (B)) as active ingredients (hereinafter also referred to as the active ingredient for suppressing the onset of stomatitis), and an extract of horsetail (component (C)).

[0013] <(A) Glycyrrhizic acid (ingredient (A))> Glycyrrhizic acid (component (A)) is a component known to have an anti-inflammatory effect in oral compositions, and the present inventors have discovered a new effect in that application of component (A) to the oral cavity before the onset of stomatitis can suppress the onset of stomatitis.

[0014] Component (A) may be used in its original form or in the form of a salt. Examples of salts of glycyrrhizinic acid include potassium salts, sodium salts, and ammonium salts, and specific examples thereof include monopotassium glycyrrhizinate, dipotassium glycyrrhizinate, monosodium glycyrrhizinate, disodium glycyrrhizinate, monoammonium glycyrrhizinate, and diammonium glycyrrhizinate. Glycyrrhizic acid is also known to be contained in plant extracts of the genus Licorice, and may be incorporated in the form of a plant extract containing glycyrrhizic acid.

[0015] The component (A) may be used in one form alone, or in a combination of two or more forms. Among these, from the viewpoints of increasing water solubility, facilitating formulation, or increasing affinity for the oral mucosa, it is preferable to use glycyrrhizinate, with potassium salts and ammonium salts of glycyrrhizinic acid being more preferable, and dipotassium glycyrrhizinate and monoammonium glycyrrhizinate being even more preferable.

[0016] <(B) Tranexamic acid (ingredient (B))> Tranexamic acid (ingredient (B)) is a type of amino acid, also known as trans-4-aminomethylcyclohexane-1-carboxylic acid, which is known to have hemostatic action due to its antiplasmin effect, anti-inflammatory action, etc. As with ingredient (A), the present inventors have discovered a new effect in that the onset of stomatitis can be suppressed by applying ingredient (B) to the oral cavity before the onset of stomatitis.

[0017] The (B) component may be used in its original form or in the form of a salt. Examples of salts of tranexamic acid include alkali metal salts such as sodium and potassium; alkaline earth metal salts such as calcium and magnesium; metal salts such as aluminum, iron, and zinc; basic amino acid salts such as lysine, arginine, histidine, and ornithine; and organic amine salts such as ammonium, monoethanolamine, diethanolamine, triethanolamine, and stearylamine. The (B) component may be used as a tranexamic acid derivative or a salt thereof, and specific examples thereof include ester derivatives such as tranexamic acid cetyl ester; and amide derivatives such as tranexamic acid methylamide. The (B) component may be used in one form alone or in a combination of two or more forms.

[0018] Although the specific mechanism by which components (A) and (B) can suppress the onset of stomatitis is unclear, it is speculated that components (A) and (B) suppress the occurrence of inflammatory edema and inflammatory cell infiltration into the oral mucosa by suppressing vascular hyperpermeability, which is an initial response to inflammation in the oral mucosa. It is known that both components (A) and (B) act on the site of inflammation, but they do not heal stomatitis, but act on healthy oral mucosa where no inflammation is present to prevent inflammation from occurring. Therefore, the effect of suppressing the onset of stomatitis and the effect of treating stomatitis are clearly distinguished.

[0019] In the composition for suppressing the onset of stomatitis, the content of at least one of the components (A) and (B) (active ingredient for suppressing the onset of stomatitis) is preferably in the range of 0.001 to 2.0 w / v% (mass / volume%). When the active ingredient for suppressing the onset of stomatitis contains the components (A) and (B), the content is the total of the components. When the content of the active ingredient for suppressing the onset of stomatitis contained in the composition for suppressing the onset of stomatitis is 0.001 w / v% or more, the effect of the present invention is more easily exhibited, and when it is 2.0 w / v% or less, the composition for suppressing the onset of stomatitis of the present invention has excellent usability as a formulation and is also highly stable, which is preferable. The content of the active ingredient for suppressing the onset of stomatitis in the composition is more preferably 0.003 w / v% or more, and even more preferably 0.005 w / v% or more. Furthermore, the upper limit is more preferably 1.85 w / v% or less, and furthermore, in order of preference, is 1.825 w / v% or less, 1.5 w / v% or less, 1.31 w / v% or less, 1.30 w / v% or less, 1.25 w / v% or less, 1.2 w / v% or less, 1.0 w / v% or less, 0.9 w / v% or less, 0.8 w / v% or less, and 0.7 w / v% or less.

[0020] In this specification, the content of the active ingredient for suppressing the onset of stomatitis means the content of glycyrrhizinic acid and / or tranexamic acid, and when the (A) component is formulated in the form of a plant extract containing glycyrrhizinic acid or used in the form of a glycyrrhizinate, the amount converted to glycyrrhizinic acid is included so as to be within the above range, and when the (B) component is used in the form of a tranexamic acid salt, a tranexamic acid derivative, or a salt thereof, the amount converted to tranexamic acid is included so as to be within the above range. The above conversion can be carried out, for example, by analyzing the plant extract containing glycyrrhizinic acid, the glycyrrhizinate, the tranexamic acid salt, the tranexamic acid derivative, or a salt thereof by a conventional method of liquid chromatography using a liquid chromatograph or a high performance liquid chromatograph, and confirming the content of glycyrrhizinic acid and tranexamic acid.

[0021] The (A) component is preferably contained in the stomatitis onset-suppressing composition in the range of 0.001 to 0.4 w / v% in terms of the amount converted to glycyrrhizinic acid. When the (A) component content is 0.001 w / v% or more, the desired effect of the present invention is easily obtained, and when it is 0.4 w / v% or less, the stomatitis onset-suppressing composition of the present invention tends to have an excellent feeling of use as a preparation and to have high preparation stability. The (A) component content is more preferably 0.003 w / v% or more, even more preferably 0.005 w / v% or more, more preferably 0.325 w / v% or less, even more preferably 0.31 w / v% or less, even more preferably 0.30 w / v% or less, particularly preferably 0.25 w / v% or less, and most preferably 0.2 w / v% or less.

[0022] The (B) component is preferably contained in the stomatitis onset-suppressing composition in an amount of 0.001 to 1.6 w / v% calculated as tranexamic acid. When the (B) component content is 0.001 w / v% or more, the desired effect of the present invention is easily obtained, and when it is 1.6 w / v% or less, the flavor and usability of the stomatitis onset-suppressing composition are not impaired and the formulation stability tends to be increased. The (B) component content is more preferably 0.003 w / v% or more, even more preferably 0.005 w / v% or more, more preferably 1.5 w / v% or less, even more preferably 1.0 w / v% or less, even more preferably 0.9 w / v% or less, particularly preferably 0.8 w / v% or less, and most preferably 0.7 w / v% or less.

[0023] In the present invention, the composition for suppressing the onset of stomatitis may contain at least one of the components (A) and (B) as an active ingredient for suppressing the onset of stomatitis, but preferably contains both the components (A) and (B). By using the components (A) and (B) in combination, the infiltration of inflammatory cells into the oral mucosa and the onset of inflammatory edema are synergistically suppressed, thereby more effectively suppressing the onset of stomatitis. When the (A) component and the (B) component are used in combination, the (A) component and the (B) component are preferably contained in a total amount of 0.002 to 2.0 w / v%. The lower limit of the total content of the (A) component and the (B) component is more preferably 0.003 w / v% or more, and even more preferably 0.005 w / v% or more. The upper limit is more preferably 1.85 w / v% or less, and the following, in order of preference, are 1.825 w / v% or less, 1.5 w / v% or less, 1.31 w / v% or less, 1.30 w / v% or less, 1.25 w / v% or less, and 1.2 w / v% or less.

[0024] In the composition for suppressing the onset of stomatitis, the content ratio A / B of the component (A) to the component (B) is preferably in the range of 0.001 to 310. When the content ratio A / B is in the above range, the effects of the present invention can be achieved. The content ratio A / B is more preferably 0.002 or more, even more preferably 0.003 or more, even more preferably 0.004 or more, particularly preferably 0.005 or more, more preferably 300 or less, even more preferably 250 or less, even more preferably 200 or less, and particularly preferably 150 or less.

[0025] <(C) Horsetail extract (ingredients (C))> The horsetail extract (component (C)) is an extract (plant extract) obtained from Equisetum arvense, a plant of the Equisetum genus in the Equisetaceae family, which is a type of herbal medicine. The present inventors have found that the horsetail extract has the effect of enhancing the efficacy of the stomatitis onset suppression active ingredient used in the present invention, i.e., ingredient (A) and / or ingredient (B), in suppressing the onset of stomatitis.

[0026] The horsetail extract can be obtained by extracting the whole plant, stems and / or leaves of the horsetail, and is preferably obtained by extracting the whole plant. Methods for obtaining the horsetail extract include solvent extraction, supercritical extraction, steam distillation, etc. The following commercially available products may also be used.

[0027] Examples of extraction solvents used in the solvent extraction treatment include water and alcohols. Examples of alcohols include methanol, ethanol, propylene glycol, 1,3-butylene glycol, or mixtures thereof, or a 1% urea-containing ethanol solution, or a 1,3-butylene glycol solution containing 1% urea. It is preferable to use an extract obtained by extraction with these solvents, and it is particularly preferable to use an extract obtained by extraction with water, methanol, ethanol, propylene glycol, 1,3-butylene glycol, or a mixture thereof.

[0028] Commercially available products of horsetail extract include, for example, "Horsetail Extract BG" (manufactured by Maruzen Pharmaceutical Co., Ltd.), "Horsetail Extract" (manufactured by Maruzen Pharmaceutical Co., Ltd.), and "Sugina Extract" (manufactured by Koei Kogyo Co., Ltd.).

[0029] In the composition for suppressing the onset of stomatitis, the content of the component (C) is preferably in the range of 0.00001 to 0.05 w / v% in terms of solid content. When the content of the component (C) contained in the composition for suppressing the onset of stomatitis is 0.00001 w / v% or more in terms of solid content, the efficacy of the active ingredient for suppressing the onset of stomatitis can be increased, and when it is 0.05 w / v% or less, the flavor and feeling of use are not impaired and the formulation stability tends to be increased. The content of the component (C) is more preferably 0.00005 w / v% or more in terms of solid content, more preferably 0.0001 w / v% or more, and even more preferably 0.045 w / v% or less, and even more preferably 0.04 w / v% or less.

[0030] The content of the component (C) in the composition for inhibiting the onset of stomatitis calculated as solid content can be measured by a conventional liquid chromatography method using a liquid chromatograph or a high performance liquid chromatograph.

[0031] The (C) component is preferably contained in an amount of 0.000005 to 50 parts by mass, calculated as solid content, per 1 part by mass of the stomatitis onset-suppressing active ingredient. When the content ratio of the (C) component to 1 part by mass of the stomatitis onset-suppressing active ingredient (C / (A+B)) is in the range of 0.000005 to 50, the desired effects of the present invention can be obtained, flavor and usability are not impaired, and formulation stability also tends to be increased. The content ratio C / (A+B) of the active ingredient for suppressing the onset of stomatitis to the (C) ingredient is more preferably 0.00001 or more, even more preferably 0.00003 or more, even more preferably 0.00005 or more, particularly preferably 0.00008 or more, and most preferably 0.0001 or more, and is more preferably 40 or less, even more preferably 35 or less, even more preferably 30 or less, even more preferably 25 or less, particularly preferably 10 or less, especially preferably 5 or less, and most preferably 1 or less.

[0032] The (C) component is preferably contained in the (A) component in an amount of 0.00003 to 50 parts by mass, calculated as solid content, per 1 part by mass of the (A) component. When the content ratio (C / A) of the (C) component to the (A) component is in the range of 0.00003 to 50, the desired effects of the present invention can be obtained and excellent palatability can be realized. The content ratio (C / A) of the (A) component to the (C) component is more preferably 0.00005 or more, even more preferably 0.00008 or more, even more preferably 0.0001 or more, particularly preferably 0.0003 or more, and most preferably 0.001 or more, and is more preferably 45 or less, even more preferably 40 or less, even more preferably 35 or less, particularly preferably 30 or less, especially preferably 10 or less, and most preferably 5 or less.

[0033] Furthermore, the (C) component is preferably contained in an amount of 0.000005 to 50 parts by mass, calculated as solid content, per 1 part by mass of the (B) component. When the content ratio (C / B) of the (C) component to the (B) component is in the range of 0.000005 to 50, the desired effects of the present invention can be obtained and excellent palatability can be realized. The content ratio (C / B) of the (B) component to the (C) component is more preferably 0.000008 or more, even more preferably 0.00001 or more, even more preferably 0.00003 or more, particularly preferably 0.00005 or more, especially preferably 0.00008 or more, and most preferably 0.0001 or more; and is more preferably 45 or less, even more preferably 40 or less, even more preferably 35 or less, and particularly preferably 30 or less.

[0034] <(D) Quaternary ammonium salt (component (D))> The composition for suppressing the onset of stomatitis of the present invention preferably further contains a quaternary ammonium salt (component (D)). Component (D) is a component known to have a bactericidal effect in oral compositions. When component (D) is contained in the composition for suppressing the onset of stomatitis of the present invention, an effective effect of suppressing the onset of stomatitis can be obtained by a synergistic effect with the active ingredient for suppressing the onset of stomatitis.

[0035] Examples of the component (D) include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, dequalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, lauroylcholaminoformylmethylpyridinium chloride, etc. The component (D) may be used alone or in combination of two or more. Among these, from the viewpoint of obtaining a high effect of suppressing the onset of stomatitis, cetylpyridinium chloride and benzethonium chloride are preferred, and cetylpyridinium chloride is more preferred.

[0036] The (D) component is preferably contained in the composition for suppressing the onset of stomatitis in the range of 0.001 to 0.15 w / v%. When the content of the (D) component is 0.001 w / v% or more, the synergistic effect with the active ingredient for suppressing the onset of stomatitis is likely to be effectively obtained, and the effect of suppressing the onset of stomatitis is likely to be effectively obtained. When the content of the (D) component is 0.15 w / v% or less, a high feeling of use can be maintained and the stability of the formulation tends to be increased. The content of the (D) component is more preferably 0.003 w / v% or more, even more preferably 0.005 w / v% or more, and more preferably 0.13 w / v% or less, and even more preferably 0.1 w / v% or less.

[0037] The content of the component (D) in the composition for suppressing the onset of stomatitis can be measured by a standard liquid chromatography method using a liquid chromatograph or a high performance liquid chromatograph.

[0038] In the composition for suppressing the onset of stomatitis, the content ratio D / A of the component (D) to the component (A) is preferably in the range of 0.003 to 150. When the content ratio D / A is in the above range, the effects of the present invention are easily exhibited. The content ratio D / A is more preferably 0.005 or more, even more preferably 0.008 or more, even more preferably 0.01 or more, particularly preferably 0.03 or more, most preferably 0.1 or more, more preferably 140 or less, even more preferably 130 or less, even more preferably 120 or less, particularly preferably 110 or less, and most preferably 100 or less.

[0039] In the composition for suppressing the onset of stomatitis, the content ratio D / B of the component (D) to the component (B) is preferably in the range of 0.001 to 150. When the content ratio D / B is in the above range, the effects of the present invention are easily exhibited. The content ratio D / B is more preferably 0.003 or more, even more preferably 0.005 or more, even more preferably 0.008 or more, particularly preferably 0.01 or more, more preferably 140 or less, even more preferably 130 or less, even more preferably 120 or less, particularly preferably 110 or less, and most preferably 100 or less.

[0040] In the composition for suppressing the onset of stomatitis, the content ratio D / (A+B) of the quaternary ammonium salt (component (D)) to the active ingredient for suppressing the onset of stomatitis (component (A) and / or component (B)) is preferably in the range of 0.0005 to 150. When the content ratio D / (A+B) is in the above range, the effects of the present invention are easily exhibited. The content ratio D / (A+B) is more preferably 0.001 or more, even more preferably 0.003 or more, even more preferably 0.005 or more, particularly preferably 0.008 or more, and most preferably 0.01 or more, and is more preferably 140 or less, even more preferably 130 or less, even more preferably 120 or less, particularly preferably 110 or less, especially preferably 100 or less, and most preferably 50 or less.

[0041] In addition, in the composition for suppressing the onset of stomatitis, the content ratio D / C of the component (D) to the component (C) is preferably in the range of 0.02 to 15,000. When the content ratio D / C is in the above range, the effect of the present invention is easily exhibited. The content ratio D / C is more preferably 0.04 or more, even more preferably 0.06 or more, even more preferably 0.08 or more, particularly preferably 0.1 or more, and most preferably 1 or more, and is more preferably 14,000 or less, even more preferably 13,000 or less, even more preferably 12,000 or less, even more preferably 11,000 or less, particularly preferably 10,000 or less, especially preferably 5,000 or less, and most preferably 1,000 or less.

[0042] The composition for suppressing the onset of stomatitis of the present invention preferably contains all of components (A), (B), (C), and (D). By containing these four components, the efficacy of suppressing the onset of stomatitis is further enhanced, and a more stable effect of suppressing the onset of stomatitis can be obtained.

[0043] The composition for suppressing the onset of stomatitis of the present invention may contain any component that can be added to an oral composition, as long as the effect of the present invention is not impaired. Examples of the optional components include solvents, sweeteners, bactericides, surfactants, anti-inflammatory agents, tartar prevention agents, pH adjusters, enzymes, ion sources, preservatives, flavorings, herbal medicines, pigments, moisturizing components, cell activation components, vitamins, amino acids, etc.

[0044] Examples of the solvent include water such as purified water and ion-exchanged water; physiological saline; lower monohydric alcohols such as ethanol; and polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol.

[0045] Examples of sweeteners include stevioside, rebaudioside, xylitol, erythritol, maltitol, sorbitol, sodium saccharin, sucralose, trehalose, reduced palatinose, aspartame, and acesulfame potassium.

[0046] Examples of disinfectants include hinokitiol, triclosan, isopropylmethylphenol, thymol, alkyldiaminoethylglycine hydrochloride solution, chlorhexidine gluconate, chlorhexidine hydrochloride, and sodium chlorite.

[0047] Examples of the surfactant include nonionic surfactants, cationic surfactants, anionic surfactants, and amphoteric surfactants. Specifically, examples of the nonionic surfactants include glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, fatty acid diethanolamides, fatty acid monoglycerides, polyoxyethylene alkyl ethers, polyoxyethylene hydrogenated castor oil, alkyl glucosides, and polyoxyethylene polyoxypropylene block copolymers. Examples of the cationic surfactants include polyoxyethylene alkylamines and fatty acid amides. Examples of the anionic surfactants include sulfate ester salts, α-olefin sulfonates, sulfosuccinates, N-acyl amino acid salts, and acylated methyl taurine salts. Examples of the amphoteric surfactants include betaine acetate amphoteric surfactants and imidazoline amphoteric surfactants.

[0048] Examples of anti-inflammatory agents include aminocaproic acid, allantoin and its derivatives, ascorbic acid and its salts, azulene, azulene sulfonate, dihydrocholesterol, epidihydrocholesterol, tocopherol acetate, tocopherol nicotinate, lysozyme chloride, and the like.

[0049] Examples of anti-tartar agents include phosphates, polyphosphates, methoxyethylene maleic anhydride copolymers, zinc chloride, zinc organic acids, edetates, and the like.

[0050] Examples of pH adjusters include sodium phosphate salts such as monosodium phosphate and disodium phosphate, sodium citrate, citric acid, glucono-δ-lactone, sodium gluconate, sodium acetate, sodium carbonate, sodium bicarbonate, sodium hydroxide, and hydrates thereof.

[0051] Examples of the enzyme include protease, dextranase, amylase, mutanase, and lysozyme.

[0052] Examples of the ion source include fluoride ion sources such as sodium fluoride, monofluorophosphate, and stannous fluoride, and calcium ion sources such as calcium phosphate, calcium gluconate, and hydroxyapatite.

[0053] Examples of preservatives include paraoxybenzoic acid esters, sodium benzoate, potassium sorbate, and phenoxyethanol.

[0054] Examples of fragrances include natural essential oils such as peppermint oil, spearmint oil, mint oil, eucalyptus oil, clove oil, thyme oil, rosemary oil, lemon oil, ginger oil, lime oil, cassia oil, cardamom oil, lavender oil, and cinnamon oil; fragrance components such as L-menthol, L-carvone, carvacrol, eugenol, anethole, 1,8-cineole, thymol, vanillin, pinene, 3-L-menthoxypropane-1,2-diol, and methyl salicylate; mixtures of these, natural fragrances, blended fragrances, and synthetic fragrances.

[0055] Examples of herbal medicines include plant extracts other than the above-mentioned horsetail extract, such as hawthorn extract, witch hazel extract, peony extract, white birch extract, sage extract, seaweed extract, Phellodendron bark extract, Angelica acutiloba extract, carrot extract, and fennel extract.

[0056] Examples of pigments include Blue No. 1, Blue No. 2, Blue No. 201, Yellow No. 4, Yellow No. 5, Yellow No. 202(1), Yellow No. 203, Red No. 3, Red No. 102, Red No. 104, Red No. 105, Green No. 3, and Green No. 201.

[0057] Moisturizing ingredients include glycerin, heparinoids (glycosaminoglycans), hyaluronic acid and its salts, petrolatum, and the like.

[0058] Examples of cell activation components include N-acetylglucosamine, γ-aminobutyric acid, acetylglucosamine, aminobutyric acid, allantoin, chlorella extract, white birch extract, white birch bark extract, taiso extract, centella asiatica extract, corn extract, jujube fruit extract, Job's tears seed extract, retinol palmitate, Belamcanda chinensis extract, bilberry leaf extract, yuzu seed extract, coix seed extract, and retinol.

[0059] Examples of vitamins include fat-soluble vitamins such as vitamin A, vitamin D, vitamin E, and vitamin K, and water-soluble vitamins such as vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, pantothenic acid, folic acid, biotin, and vitamin C.

[0060] Amino acids include valine, isoleucine, leucine, methionine, lysine (lysine), phenylalanine, tryptophan, threonine (threonine), histidine, arginine, glycine, alanine, serine, tyrosine, cysteine, asparagine, glutamine, proline, aspartic acid, glutamic acid, and the like.

[0061] The composition for suppressing the onset of stomatitis of the present invention can be prepared by heating component (A) and / or component (B), component (C), and optionally component (D) and other optional components, as necessary, and stirring and mixing each component uniformly.

[0062] The composition for suppressing the onset of stomatitis of the present invention can be prepared in the form of, for example, a liquid, a gel, a paste, a solid, etc. Examples of the form of the composition for suppressing the onset of stomatitis include toothpastes such as toothpaste and liquid dentifrice, mouthwash, mouthspray, mouthwash (gargle), oral application agent, oral patch, nebulizer, troche, chewing gum, candy, etc. Among these, liquid preparations such as liquid dentifrice, mouthwash, mouthspray, and mouthwash are preferred because the active ingredient can be uniformly applied to the oral cavity.

[0063] In this specification, the term "liquid" refers to a material that has fluidity and has a viscosity of 20 mPa s or less, preferably 10 mPa s or less, at 20° C. Here, the viscosity can be measured using a commercially available rotational viscometer (for example, a B-type viscometer manufactured by Toki Sangyo Co., Ltd.).

[0064] Methods for using the composition for suppressing the onset of stomatitis of the present invention include regularly and at desired times, placing it in the oral cavity to rinse the oral cavity, applying it to the oral mucosa, etc. Specifically, when used as a mouthwash, about 5 to 30 mL of the composition for suppressing the onset of stomatitis of the present invention may be placed in the mouth and the oral cavity may be rinsed for about 5 to 30 seconds. In addition, the number of times that the composition for suppressing the onset of stomatitis of the present invention is used is not particularly limited, but continuous use makes it easier to maintain the effect of suppressing the onset of stomatitis. For example, it is preferable to use it three or more times a day for one month or more.

[0065] (Stomatitis suppression potentiator) The present invention also provides an enhancer for enhancing the efficacy of at least one of the components (A) and (B) in suppressing the onset of stomatitis. By incorporating the enhancer for suppressing the onset of stomatitis of the present invention in a composition for suppressing the onset of stomatitis containing at least one of the components (A) and (B) as an active ingredient, the efficacy of suppressing the onset of stomatitis can be increased.

[0066] The stomatitis onset suppression efficacy enhancer of the present invention contains an extract of horsetail (ingredient (C)) as an active ingredient. Component (C) is as described above, and an extract obtained by extraction processing from the whole plant, stems and / or leaves of horsetail may be used, but an extract obtained by extraction processing from the whole plant of horsetail is preferred, and a commercially available product may also be used.

[0067] The content of the (C) component in the stomatitis onset suppression efficacy enhancer is preferably 0.00001% by mass or more, calculated as the solid content. When the content of the (C) component in the stomatitis onset suppression efficacy enhancer is 0.00001% by mass or more, the efficacy of suppressing the onset of stomatitis can be increased by adding the stomatitis onset suppression efficacy enhancer to the stomatitis onset suppression composition. The content of the (C) component in the stomatitis onset suppression efficacy enhancer is more preferably 0.0005% by mass or more, even more preferably 0.0008% by mass or more, and may be 100% by mass, i.e., the enhancer is composed of the (C) component.

[0068] Other components that can be contained in the stomatitis onset suppression efficacy enhancer are not particularly limited as long as they do not inhibit the stomatitis onset suppression effect when contained in the stomatitis onset suppression composition. For example, the optional components that can be contained in the stomatitis onset suppression composition described above can be included.

[0069] The content of the stomatitis onset suppression efficacy enhancer in the stomatitis onset suppression composition is not particularly limited, but is contained so that the (C) component is in the range of 0.00001 to 0.05 w / v% in terms of solid content. When the stomatitis onset suppression efficacy enhancer is contained so that the (C) component is contained in the stomatitis onset suppression composition in an amount equivalent to 0.00001 w / v% or more in terms of solid content, the efficacy of the stomatitis onset suppression active ingredient can be enhanced, and when it is 0.05 w / v% or less, the flavor and feeling of use are not impaired and the formulation stability also tends to be increased. The stomatitis onset suppression efficacy enhancer is preferably used in an amount such that the content of component (C) in the stomatitis onset suppression composition is 0.00005 w / v% or more, preferably 0.0001 w / v% or more, calculated as solids content, and more preferably 0.045 w / v% or less, more preferably 0.04 w / v% or less. EXAMPLES

[0070] The present invention will be further explained below with reference to the following test examples, but is not limited to these examples. In the following table, the content of cetylpyridinium chloride hydrate is the content calculated as cetylpyridinium chloride, and the content of horsetail extract is the content calculated as solid content. The converted amount of glycyrrhizinic acid was calculated by analyzing the dipotassium glycyrrhizinate used using a high performance liquid chromatograph and confirming the content of glycyrrhizinic acid.

[0071] <Test Example 1: Evaluation of the effect of suppressing the onset of stomatitis 1> (Examples 1 to 5) According to the formulations shown in Table 1, liquid samples of Examples 1 to 5 were prepared and subjected to the following tests.

[0072] (Comparative Examples 1 to 2) According to the formulations shown in Table 1, liquid samples of Comparative Examples 1 and 2 were prepared and similarly tested.

[0073] (Reference example 1) According to the formulation shown in Table 1, a liquid sample of Reference Example 1 was prepared and similarly tested.

[0074] (Control Example 1) A similar test was performed using physiological saline (Otsuka Saline Injection, Japanese Pharmacopoeia, manufactured by Otsuka Pharmaceutical Co., Ltd.).

[0075] [Table 1]

[0076] [Test to confirm the effect of suppressing the onset of stomatitis] (Test animals) For the test, 5-week-old male Syrian hamsters (Japan SLC Co., Ltd.) that had been reared for one week were used. The hamsters were housed in a cage of three in a controlled environment (temperature: 22°C, humidity: 50±10% RH, lighting from 8:00 to 20:00), with free access to water and food.

[0077] (Test Method) 1) Hamsters (Syrian, male, 5 weeks old) that had been kept for one week were given 50 μL of the above liquid sample applied to the right buccal mucosa twice a day for six consecutive days. 2) On the fifth and sixth days, 50 μL of the above liquid sample was applied to the right buccal mucosa of the anesthetized hamsters, and then a Φ6 mm filter paper soaked in a 30 (w / v)% aqueous solution of acetic acid was attached for 10 seconds. After that, 50 μL of the above liquid sample was applied again to the right buccal mucosa to induce stomatitis (inflammatory edema). 3) On the seventh day, the severity of the wound was evaluated based on the following criteria, and the average value was recorded as the value for each example. <Evaluation criteria (stomatitis score)> Score 0: No inflammatory edema. Score 1: The mucosal surface is rough, but no inflammatory edema is observed. Score 2: Inflammatory edema is present, the area of ​​which is smaller than that of an acetic acid-impregnated filter paper. Score 3: Inflammatory edema is present, the area of ​​which is larger than that of acetic acid-impregnated filter paper.

[0078] The results are shown in Table 2 and FIG.

[0079] [Table 2]

[0080] From Table 2 and Figure 1, it was found that Examples 1 to 5 had high efficacy in suppressing the onset of stomatitis and had excellent effects of suppressing the onset of stomatitis. Comparative Examples 1 and 2 did not show a significant effect of suppressing the onset of stomatitis compared to Control Example 1. Comparing Examples 1 to 3 with Comparative Example 1, it was found that the effect of suppressing the onset of stomatitis was due to the active ingredients glycyrrhizinic acid and tranexamic acid. Furthermore, by comparing Example 1, Comparative Example 2, and Reference Example 1, it was found that although horsetail extract does not have the effect of suppressing the onset of stomatitis, its efficacy in suppressing the onset of stomatitis is enhanced when used together with glycyrrhizinic acid and / or tranexamic acid.

[0081] <Test Example 2: Evaluation of the effect of suppressing the onset of stomatitis 2> (Examples 6 to 9) According to the formulations shown in Table 3, liquid samples of Examples 6 to 9 were prepared.

[0082] (Reference examples 2~5) According to the formulations shown in Table 3, liquid samples of Reference Examples 2 to 5 were prepared.

[0083] [Table 3]

[0084] [Test to confirm the effect of suppressing the onset of stomatitis] The stomatitis score of each subject was evaluated in the same manner as in Test Example 1. The results are shown in Table 4 and FIG.

[0085] [Table 4]

[0086] Comparisons between Example 6 and Reference Example 2, Example 7 and Reference Example 3, Example 8 and Reference Example 4, and Example 9 and Reference Example 5 revealed that the effect of horsetail extract in suppressing the onset of stomatitis caused by glycyrrhizinic acid and tranexamic acid is enhanced. Moreover, it was confirmed from Test Examples 1 and 2 that the effect could be exhibited at least when the horsetail extract concentration (converted into solid content) was in the range of 0.0001 to 0.02 w / v %.

[0087] <Test Example 3: Evaluation of stomatitis healing effect> The following tests were carried out using the liquid samples of Example 1, Comparative Example 1, Reference Example 1 and Control Example 1 prepared in Test Example 1.

[0088] (Test animals) For the test, 5-week-old male Syrian hamsters (Japan SLC Co., Ltd.) that had been reared for one week were used. The hamsters were housed in a cage of three in a controlled environment (temperature: 22°C, humidity: 50±10% RH, lighting from 8:00 to 20:00), with free access to water and food. Four to five hamsters were provided for each experiment.

[0089] (Test Method) 1) A hamster (Syrian, male, 5 weeks old) that had been reared for one week was fixed to a corkboard under anesthesia, and 30 μL of 10 (w / v)% acetic acid saline was injected intradermally into the right cheek pouch under anesthesia to induce stomatitis. 2) After measuring the major and minor diameters of the wound under anesthesia, 50μL of the liquid sample was applied to the wound per mouse. The liquid sample was applied once a day for six consecutive days. 3) The stomatitis healing rate (%) was calculated for each day using the following formula (1), and the average value was calculated. Samples were processed from day 1 to day 6, but on day 7, no sample processing was performed and only the wound area was measured. Stomatitis healing rate (%) = (wound area at the time of wound creation (mm 2 )-Wound area at time of measurement (mm 2 )) / wound area at the time of wound creation (mm 2 )}×100 ···(1) Wound area (mm 2 ) = major axis (mm) x minor axis (mm)

[0090] The results are shown in Figure 3.

[0091] Example 1 had a superior stomatitis healing effect compared to Comparative Example 1 and Control Example 1, and also had a stomatitis healing effect equivalent to that of Reference Example 1. Therefore, it is believed that the effect was due to the glycyrrhizinic acid and tranexamic acid added as active ingredients.

[0092] From Test Example 1 and Test Example 3, it was found that Example 1 has a higher efficacy in suppressing the onset of stomatitis than Reference Example 1, while its efficacy in curing stomatitis is equivalent to that of Reference Example 1. This suggests that the mechanisms of suppressing the onset of stomatitis and treating stomatitis are different, and it was found that Examples 1 to 9 provide an excellent effect of suppressing the onset of stomatitis.

Claims

1. A composition for suppressing the onset of stomatitis, comprising as active ingredients at least one of (A) glycyrrhizinic acid and (B) tranexamic acid, and (C) an extract of horsetail.

2. (C) An agent for enhancing the efficacy of suppressing the onset of stomatitis, comprising at least one of (A) glycyrrhizinic acid and (B) tranexamic acid, and containing an extract of horsetail as an active ingredient.

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