JP6243849B2 - Oral composition and oral oxygen scavenger - Google Patents

Description

  The present invention relates to an oral composition.

  Periodontal disease is an infection caused by bacteria, mainly anaerobic gram-negative bacteria such as P. gingivalis, and exotoxins (such as leukotoxin) and endotoxins (such as lipopolysaccharide) produced by the bacteria. ) Induces inflammation and damages the tissue. Therefore, the development of bactericides and antibacterial agents has been promoted in order to eliminate periodontal pathogenic bacteria.

  On the other hand, in vivo, neutrophils and lymphocytes infiltrate the periodontal pockets and gingival tissues, phagocytose periodontopathic bacteria, and produce an immune response that eliminates these foreign substances by creating specific antibodies. . However, in recent years, it has been pointed out that active oxygen excessively generated during phagocytosis further damages living tissues and causes periodontal disease to progress. It has also been reported that toxins remain even after periodontopathic bacteria die, and inflammation caused by the toxins continues to produce new active oxygen. In addition, environmental factors such as smoking and stress have been reported to increase active oxygen.

  Bactericides and antibacterial agents are desirable to have “immediate effects” that immediately exert their effects. However, active oxygen changes depending on chemical reactions such as hydrogen peroxide, hydroxy radicals, superoxide, etc., and continues as inflammation progresses. Produced. Therefore, in order to remove these active oxygen species, “long-lasting” is desirable in addition to “high removal effect”.

  For example, when fibroblasts constituting the gingiva are injured by reactive oxygen species, collagen fibers are destroyed and the cell growth ability is reduced, and thus the gingiva is retracted and periodontal disease progresses. Therefore, the development of antioxidants that remove these active oxygen species is underway.

  As an antioxidant, for example, ascorbic acid phosphate, which is a derivative of ascorbic acid, is more stable than ascorbate and suppresses inflammation by eliminating excess active oxygen produced in the body. Effects have been reported, and application technologies to oral compositions such as toothpastes and lozenges (Patent Document 1) and techniques for improving mucosal absorbability using a cationic polymer in combination (Patent Document 2) are being studied. . Vitamin E and its derivatives, known as fat-soluble antioxidants, are commonly used as antioxidants for foods and pharmaceuticals (Patent Document 3), and are also used to improve retention by hydrogel particles (Patent Document 4). Etc. have been proposed. Astaxanthin and fucoxanthin are also antioxidants that attract attention due to their high effects. They are blended into pharmaceutical compositions (Patent Document 5), sunburn and blotch reduction techniques (Patent Document 6), and ingested in the blood by food intake. A technique for reducing active oxygen (Patent Document 7) and the like have been proposed.

JP-A-2-292211 JP 2004-83543 A JP-A-10-53515 JP 2009-196987 A JP 2008-1623 A JP 2008-239606 A International Publication No. 04/052385

  However, at present, the technology for utilizing antioxidant substances from the viewpoint of periodontal disease prevention is still insufficient. Since saliva and gingival crevicular fluid always flow out and flow in the oral cavity, it is very difficult to allow an antioxidant to act effectively for a long time around the periodontal tissue.

  In order to erase the active oxygen in the cells that make up the gingiva for a long time, it is necessary to allow an antioxidant to effectively act on the periodontal tissue for a long time in a situation where gingival environmental fluid such as saliva flows. It becomes important. According to a survey of dental diseases, it is pointed out that the number of people suffering from periodontal disease is as high as 80% of the population, and the development of an oral composition that can further improve the effect of preventing periodontal disease is desired.

  This invention is made | formed in view of the said situation, and aims at providing the composition for oral cavity which has the high periodontal disease prevention effect by erase | eliminating the active oxygen in the cell which comprises gingiva for a long time. .

  As a result of intensive studies to achieve the above object, the present inventors have used reactive lactam compounds in combination with antioxidants to reduce the active oxygen in gingival constituent cells even in an environment where saliva flow is assumed. It has been found that it can be erased for a long time, and the present invention has been completed.

That is, the present invention provides the following [1] to [5].
[1] (A) A lactam compound having an acidic group selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, and 3- (2-oxo-1-azepanyl) propanoic acid and / or a salt thereof And (B) composition for oral cavity containing antioxidant substance.
[2] The composition for oral cavity according to [1], wherein the component (A) is pyrrolidonecarboxylic acid and / or a salt thereof.
[3] The component (B) is one or more antioxidants selected from the group consisting of ascorbic acid and its derivatives, vitamin E and its derivatives, astaxanthin, and fucoxanthin, according to [1] or [2] Oral composition.
[4] The composition for oral cavity according to [1] or [2], wherein the component (B) is one or more antioxidants selected from the group consisting of ascorbic acid phosphate, vitamin E and derivatives thereof.
[5] (A) A lactam compound having an acidic group selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, and 3- (2-oxo-1-azepanyl) propanoic acid and / or a salt thereof And (B) an active oxygen scavenger containing an antioxidant as an active ingredient.

  ADVANTAGE OF THE INVENTION According to this invention, the composition for oral cavity which has the high periodontal disease prevention effect by erase | eliminating the active oxygen in the cell which comprises a gingiva for a long time can be provided.

  Hereinafter, the present invention will be described in detail with reference to preferred embodiments thereof.

[Oral composition]
The composition for oral cavity of the present invention is a lactam having an acidic group selected from the group consisting of (A) pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, and 3- (2-oxo-1-azepanyl) propanoic acid. A compound and / or a salt thereof, and (B) an antioxidant.

<(A) component>
The component (A) contained in the oral composition of the present invention is selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, and 3- (2-oxo-1-azepanyl) propanoic acid. A lactam compound having an acidic group and / or a salt thereof.

  In the present invention, by using such component (A) in combination with the antioxidant substance (B), the active oxygen in the cells constituting the gingiva can be erased for a long period of time, thereby preventing periodontal disease. The composition for oral cavity which has this is implement | achieved. That is, the component (A) has an effect of improving the persistence of the intracellular active oxygen scavenging effect of the antioxidant substance.

  When the component (A) is in the form of a salt, the salt is not particularly limited as long as it is a pharmacologically acceptable salt. Examples of pharmacologically acceptable salts include acid addition salts, base addition salts, and amino acid salts. Specific examples thereof include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, hydroiodide, nitrate, phosphate; citrate, oxalate, acetate, formate, propion Acid salt, benzoate salt, trifluoroacetate salt, maleate salt, tartrate salt, methanesulfonate salt, benzenesulfonate salt, paratoluenesulfonate salt, etc .; sodium salt, potassium salt, calcium salt, magnesium Inorganic base salts such as salts and ammonium salts; organic base salts such as triethylammonium salt, triethanolammonium salt, pyridinium salt and diisopropylammonium salt; and amino acid salts such as arginine salt, aspartate and glutamate. Among these salts, water-soluble salts are preferred, inorganic base salts are preferred, alkali metal salts are more preferred, and sodium salts and potassium salts are particularly preferred.

  From the viewpoint of increasing the sustainability of the active oxygen scavenging effect of the component (B), the component (A) is particularly preferably pyrrolidone carboxylic acid and / or a salt thereof.

  The lactam compound or salt thereof used as the component (A) can be synthesized according to a known scheme. Or the lactam compound used as (A) component or its salt may use a commercial item.

  As a commercial item of pyrrolidone carboxylic acid, for example, “AJIDE A-100 (registered trademark)” sold by Ajinomoto Co., Inc. may be mentioned. As a commercial item of sodium pyrrolidonecarboxylate, for example, “AJIDEW NL-50 (registered trademark)” sold by Ajinomoto Co., Inc. may be mentioned.

  Examples of commercially available 6-oxo-2-piperidinecarboxylic acid include “(S) -6-Oxo-2-piperidine carboxylic acid (trade name)” sold by Sigma Aldrich Japan Co., Ltd.

  As a commercial item of 3- (2-oxo-1-azepanyl) propanoic acid, for example, “3- (2-Oxoazepan-1-yl) propanoic acid (trade name)” sold by Sigma Aldrich Japan Co., Ltd. Is mentioned.

  In the composition for oral cavity of the present invention, the component (A) may be used alone or in combination of two or more.

  The content of the component (A) in the oral composition of the present invention is preferably 0.1% by mass or more and 0.5% by mass or more from the viewpoint of enhancing the sustainability of the active oxygen scavenging effect. Is more preferable, and it is further more preferable that it is 1 mass% or more.

  The upper limit of the content of the component (A) in the oral composition of the present invention is preferably 10% by mass or less, and preferably 5% by mass or less from the viewpoints of sustainability of the active oxygen scavenging effect and formulation stability. It is more preferable.

  In one embodiment, the content of the component (A) in the oral composition of the present invention is preferably 0.1 to 10% by mass, and 0.5 to 5% by mass with respect to the total amount of the oral composition. % Is more preferable, and 1 to 5% by mass is even more preferable.

  In addition, in this invention, content of each component in an oral composition is based on the preparation amount of each component at the time of manufacturing a composition.

<(B) component>
(B) component contained in the composition for oral cavity of this invention is an antioxidant substance.

  Examples of antioxidants that can be suitably used as the component (B) include ascorbic acid and its derivatives, vitamin E and its derivatives, astaxanthin, fucoxanthin, glutathione, uric acid, β-carotene, vitamin A, ubiquinol, and flavonoids Etc. Here, ascorbic acid derivatives include, for example, ascorbic acid phosphate salts such as magnesium ascorbic acid phosphate and sodium ascorbic acid phosphate. Examples of vitamin E derivatives include tocopherol acetate and tocopherol nicotinate.

  (A) From the viewpoint of showing the durability of the active oxygen scavenging effect excellent in combination with the component (B), the component (B) is selected from the group consisting of ascorbic acid and its derivatives, vitamin E and its derivatives, astaxanthin, and fucoxanthin. One or more selected antioxidants are preferred, one or more antioxidants selected from the group consisting of ascorbic acid phosphate, vitamin E and its derivatives, astaxanthin, and fucoxanthin are more preferred, and ascorbic acid phosphate One or more antioxidants selected from the group consisting of salts and vitamin E and derivatives thereof are more preferable, and one or more antioxidants selected from the group consisting of magnesium ascorbate phosphate and tocopherol acetate are particularly preferable.

  The antioxidant used as the component (B) can be synthesized according to a known scheme. Alternatively, a commercially available product may be used as the antioxidant used as component (B).

  In the composition for oral cavity of the present invention, the component (B) may be used alone or in combination of two or more.

  The content of the component (B) in the oral composition of the present invention is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, from the viewpoint of enhancing the sustainability of the active oxygen scavenging effect. More preferably, the content is 0.1% by mass or more.

  The upper limit of the content of the component (B) in the oral composition of the present invention is preferably 2% by mass or less and more preferably 1% by mass or less from the viewpoint of formulation stability.

  In one embodiment, the content of the component (B) in the oral composition of the present invention is preferably 0.01 to 2% by mass, and 0.05 to 1% by mass with respect to the total amount of the oral composition. % Is more preferable, and 0.1 to 1% by mass is even more preferable.

  There exists a preferable range in the compounding ratio of (A) component and (B) component. That is, from the viewpoint of formulation stability, the mass ratio of the component (A) to the component (B) [(A) component / (B) component] in the oral composition of the present invention is preferably 1 or more. More preferably, it is 2 or more. In addition, from the viewpoint of sustainability of the active oxygen scavenging effect, the mass ratio of the (A) component to the (B) component [(A) component / (B) component] in the oral cavity composition of the present invention is 100 or less. It is preferable that it is 30 or less. In order to achieve both the sustainability of the active oxygen scavenging effect and the preparation stability at a high level, it is preferably 1 to 100, and more preferably 2 to 30.

  The shape and dosage form of the composition for oral cavity of the present invention are not particularly limited. For example, it can be prepared in various shapes such as a liquid system (liquid, liquid, paste) and a solid system (solid, solid). Examples of dosage forms include toothpaste compositions such as toothpaste, liquid dentifrice, liquid dentifrice, powder dentifrice, mouthwash composition, coating composition, oral pasta, mouth freshener composition, food form (for example, Chewing gum, tablet confectionery, candy, gummi, film, troche, etc.).

  In addition to the above components, the oral composition of the present invention contains a known additive component (pharmacologically acceptable carrier) that can be used for the oral composition within a range not impairing the effects of the present invention. Can be blended. Examples of such additional components include abrasives, binders, thickeners, surfactants, sweeteners, preservatives, fragrances, medicinal ingredients, colorants, brighteners, pH adjusters, solvents, excipients. And can be appropriately selected depending on the dosage form. Although the specific example of an additional component is shown below, the component which can be mix | blended with the composition for oral cavity of this invention is not restrict | limited to these.

  Examples of the abrasive include silica-based abrasives such as silicic anhydride, crystalline silica, amorphous silica, silica gel, aluminosilicate, zeolite, calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, Examples thereof include calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, tribasic magnesium phosphate, zirconium silicate, tertiary calcium phosphate, hydroxyapatite, tetracalcium phosphate, and a synthetic resin abrasive.

  An abrasive | polishing agent can be used individually by 1 type or in combination of 2 or more types. When mix | blending an abrasive | polishing agent, it is preferable that the compounding quantity is 2-40 mass% of the whole composition in a dentifrice, and it is more preferable that it is 5-20 mass%. In a mouthwash, it is preferable that it is 0-10 mass% of the whole composition, and it is more preferable that it is 0-5 mass%.

  Examples of the binder include pullulan, gelatin, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, carrageenan, sodium alginate, xanthan gum, sodium polyacrylate, gum arabic, guar gum, locust bean gum, polyvinyl alcohol, polyvinyl Examples include pyrrolidone and carboxyvinyl polymer. A binder can be used individually by 1 type or in combination of 2 or more types. The compounding quantity in the case of using a binder is usually 0.01-3 mass% with respect to the whole composition.

  Examples of the thickening agent (wetting agent) include sorbitol, propylene glycol, butylene glycol, glycerin, polyethylene glycol and the like. A thickener can be used individually by 1 type or in combination of 2 or more types. When using a thickener, the compounding quantity can be defined in the range which does not prevent the effect of this invention, and is 1-60 mass% normally with respect to the whole composition.

  Examples of the surfactant include an anionic surfactant and a nonionic surfactant.

  Examples of the anionic surfactant include N-acyl amino acid salts, α-olefin sulfonates, N-acyl sulfonates, alkyl sulfates, sulfates of glycerol fatty acid esters, and the like. Of these, N-acylamino acid salts, α-olefin sulfonates, alkyl sulfates and the like are preferable from the viewpoint of versatility, and lauroyl sarcosine sodium, alkyl chain carbon chain length from the viewpoint of foamability and hard water resistance. More preferred are sodium α-olefin sulfonates having 10 to 16 carbon atoms, sodium lauryl sulfate, and the like.

  Nonionic surfactants include, for example, polyoxyethylene alkyl ether, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene hydrogenated castor oil, glycerin ester polyoxyethylene ether, sucrose fatty acid ester, alkylolamide And glycerin fatty acid ester. Of these, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, alkylolamide, sorbitan fatty acid ester and the like are preferably used from the viewpoint of versatility. The polyoxyethylene alkyl ether preferably has a carbon chain length of 14 to 18 carbon atoms. The polyoxyethylene alkyl ether preferably has an average ethylene oxide addition mole number of 15 to 30. The polyoxyethylene hydrogenated castor oil preferably has an ethylene oxide average addition mole number (average addition EO) of 20 to 100. The alkylolamide preferably has an alkyl chain with a carbon chain length of 12 to 14 carbon atoms. The sorbitan fatty acid ester preferably has 12 to 18 carbon atoms in the fatty acid. The polyoxyethylene sorbitan fatty acid ester preferably has 16 to 18 carbon atoms in the fatty acid. In addition, the polyoxyethylene sorbitan fatty acid ester preferably has an average ethylene oxide addition mole number of 10 to 40.

  Surfactant can be used individually by 1 type or in combination of 2 or more types. The amount of the surfactant used is usually 0 to 10% by mass, preferably 0.01 to 5% by mass, based on the entire composition.

  Examples of the sweetening agent include saccharin sodium, stevioside, neohesperidin hydrochalcone, glycyrrhizin, perilartin, p-methoxycinnamic aldehyde, thaumatin, palatinose, maltitol, xylitol, arabitol and the like. A sweetener can be used individually by 1 type or in combination of 2 or more types. When a sweetener is used, the blending amount can be appropriately determined within a range not impairing the effects of the present invention.

  Examples of the preservative include paraoxybenzoic acid esters such as sodium benzoate, methylparaben, ethylparaben, and butylparaben, ethylenediaminetetraacetate, benzalkonium chloride, and the like. A preservative can be used individually by 1 type or in combination of 2 or more types. When the preservative is used, the blending amount can be appropriately determined within a range not impairing the effects of the present invention.

  Examples of the fragrances include natural fragrances, synthetic fragrances (single fragrances), and blended fragrances (oil and fat fragrances (oil-based fragrances), powder fragrances, and the like). A fragrance | flavor can be used individually by 1 type or in combination of 2 or more types.

  Natural flavors include, for example, mastic oil, parsley oil, anise oil, eucalyptus oil, winter green oil, cassia oil, menthol oil, spearmint oil, peppermint oil, lemon oil, coriander oil, orange oil, mandarin oil, lime oil , Lavender oil, laurel oil, chamomile oil, cardamom oil, caraway oil, bay oil, lemongrass oil, pine needle oil, neroli oil, rose oil, jasmine oil, Iris concrete, peppermint absolute, rose absolute, orange flower, citrus Oil, mixed fruit oil, strawberry oil, cinnamon oil, clove oil, grape oil, thyme oil, sage oil, mint oil, rosemary oil, marjoram oil, origanum oil, grapefruit oil, sweetie oil, coconut oil, mango absolute Chute, orange flower absolute, capsicum extract, ginger oleoresin, pepper oleoresin, and capsicum oleoresin and the like.

  Single flavors include, for example, carvone, anethole, methyl salicylate, cinnamaldehyde, linalool, linalyl acetate, limonene, menthone, menthyl acetate, pinene, octyl aldehyde, citral, pregon, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate Rate, allylcyclohexanepropionate, methylanthranilate, ethylmethylanthranilate, vanillin, undecalactone (γ-undecalactone, δ-undecalactone, etc.), hexanal (trans-2-hexenal, etc.), ethi Non-alcohol, propyl alcohol, butanol, isoamyl alcohol, hexenol (such as cis-3-hexenol), dimethylsulfide, cycloten, furfural, Limethylpyrazine, ethyl lactate, ethyl lioacetate, cineol (1,8-cineole, etc.), eugenol, mensofuran, linalool oxide, vanillyl butyl ether, isopulegol, furaneol, ethylcyclopentenolone, 2-methylbutyric acid, propio Nick acid, decalactone (γ-decalactone, δ-decalactone etc.), nonalactone (γ-nonalactone, δ-nonalactone etc.), hexalactone (γ-hexalactone, δ-hexalactone etc.), isoamyl acetate, benzaldehyde, hexyl acetate, Ethyl-2-methylbutyrate, benzyl alcohol, α-terpineol, phenylethyl glycidate, phenylethyl alcohol, allyl hexanoate, methylcin Formate, ethyl β- methylthio propionate, cis-6-nonenol, Caron, methyl jasmonate like. As a single flavor, menthol, N-ethyl-p-menthane-3-carboxamide, N- (ethoxycarbonylmethyl) -3-p-menthane carboxamide, N, 2,3-trimethyl-2-isopropylbutanamide , 3- (L-methoxy) propane-1,2-diol, menthyl lactate (menthyl lactate), monomenthyl succinate, menthose glycerol acetal, 3-l-menthoxypropane-1,2-diol, menthose glycerol ether, spiranthol And monomenthyl succinate.

  The blended fragrance is a fragrance made by blending a single fragrance and / or a natural fragrance. Examples include menthol micron, strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, tropical fruit flavor, butter flavor, milk flavor, yogurt flavor, fruit mix flavor, herbal mint flavor and the like.

  The form of the fragrance is not limited, and any of essential oil, extract, solid, and powder obtained by spray-drying any of these may be used. It is preferable to use 0.000001-1 mass% of said fragrance | flavor raw material in a formulation composition. Moreover, it is preferable to use 0.1-2.0 mass% of the fragrance | flavor for perfume using the said fragrance | flavor raw material in a formulation composition.

  Examples of the medicinal component include the following components: bactericidal or antibacterial agents such as chlorohexidine, triclosan, isopropylmethylphenol, cetylpyridinium chloride, zinc gluconate, zinc citrate; condensed phosphate, ethane hydroxydiphosphonate Anti-inflammatory agents such as tranexamic acid, glycyrrhizic acid dipotassium salt, ε-aminocaproic acid, and apricot extract; coating agents such as hydroxyethylcellulose dimethyldiallylammonium chloride; allantochlorhydroxyaluminum, vitamin C, lysozyme chloride, Astringents such as glycyrrhetinic acid and its salts, sodium chloride and allantoin; hypersensitivity inhibitors such as strontium chloride. The compounding amount in the case of using a medicinal component can be appropriately set within a pharmaceutically acceptable range for each medicinal component.

  Examples of the colorant include natural pigments such as safflower red pigment, gardenia yellow pigment, gardenia blue pigment, perilla pigment, red potato pigment, red cabbage pigment, carrot pigment, hibiscus pigment, cacao pigment, spirulina pigment, and coumarindo pigment. Red 3, No. 104, Red No. 105, Red No. 106, Yellow No. 4, Yellow No. 5, Green No. 3, Blue No. 1 and other legal dyes, riboflavin, copper chlorofin sodium, titanium dioxide and the like. . When mix | blending a coloring agent, it is preferable that the compounding quantity is 0.00001-3 mass% with respect to the whole composition.

  Examples of the brightener include waxes such as shellac, carnauba wax, and candelilla wax, and calcium stearate. When the brightener is blended, the blending amount is preferably 0.01 to 5% by mass with respect to the entire composition.

  The pH (20 ° C.) of the oral composition of the present invention is usually 6 to 10, preferably 6 to 9. Examples of the pH adjuster include acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, malic acid, gluconic acid, maleic acid, succinic acid, glutamic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, Examples include acids and alkalis such as sodium citrate, sodium hydrogen citrate, sodium phosphate, and sodium dihydrogen phosphate, and buffers. When a pH adjuster is blended, the blending amount can be appropriately determined within a range not impairing the effects of the present invention.

  Examples of the solvent include water and lower alcohols having 3 or less carbon atoms such as ethanol and propanol. The solvent is usually blended in a liquid oral composition. When water is blended as a solvent, the blending amount is preferably 20 to 95% by mass with respect to the entire composition. When a lower alcohol is blended as a solvent, the blending amount is preferably 1 to 20% by mass with respect to the entire composition.

  Examples of excipients include syrup, glucose, fructose, invert sugar, dextrin, oligosaccharide and the like. When the oral composition is a food preparation, an excipient is usually added. When the excipient is blended, the blending amount can be appropriately determined within a range not impairing the effects of the present invention.

[Active oxygen scavenger]
The active oxygen scavenger of the present invention is a lactam having an acidic group selected from the group consisting of (A) pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, and 3- (2-oxo-1-azepanyl) propanoic acid. A compound and / or a salt thereof and (B) an antioxidant are contained as active ingredients.

  The compounding ratio of the component (A) and the component (B) in the active oxygen scavenger of the present invention can be the same as the compounding ratio described in [Composition for oral cavity] above.

  The active oxygen targeted by the active oxygen scavenger of the present invention is not particularly limited. Among them, the active oxygen scavenger of the present invention is excellent in sustaining the active oxygen scavenging effect even in an environment where gingival environmental fluid such as saliva flows, and is used to remove active oxygen in gingival constituent cells. It is preferable to do.

  The administration form of the active oxygen scavenger of the present invention is not particularly limited. For example, oral administration (for example, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, transdermal) Administration, nasal administration, pulmonary administration, etc.). Among these, a less invasive dosage form is preferable, and oral administration or transdermal administration is more preferable.

  The subjects who take the active oxygen scavenger of the present invention are subjects who have already developed symptoms due to active oxygen (for example, periodontal tissue trouble (gingival recession, etc.)) Examples include subjects who have no symptoms but want to prevent. The administration time of the agent of the present invention is not particularly limited.

  Hereinafter, the present invention will be described in detail with reference to examples. Examples 1 to 37 and Comparative Examples 1 to 7 described below are for explaining the present invention preferably, and the present invention is not limited to the examples described below.

The main raw materials used in Examples 1 to 37 and Comparative Examples 1 to 7 described below are collectively described below.
[Main raw materials used in Examples and Comparative Examples]
<(A) component>
(A-1): Pyrrolidone carboxylic acid “AJIDE A-100 (registered trademark)” manufactured by Ajinomoto Co., Inc.
(A-2): 6-oxo-2-piperidinecarboxylic acid Sigma Aldrich Japan, trade name “(S) -6-Oxo-2-piperidinecarboxylic acid”
(A-3): 3- (2-oxo-1-azepanyl) propanoic acid manufactured by Sigma Aldrich Japan, trade name “3- (2-Oxoazepan-1-yl) propanoic acid”
<(B) component>
(B-1): Magnesium ascorbyl 2-phosphate ester manufactured by Showa Denko KK, trade name “PM ascorbic acid”
(B-2): Tocopherol acetate, manufactured by DSM Nutrition Japan, trade name “tocopherol acetate”
(B-3): Astaxanthin Wako Pure Chemical Industries, grade “for cell biology”
(B-4): Fucoxanthin Wako Pure Chemical Industries, Grade “For cell biology”
<Other additive components>
Propylene glycol (viscous agent), hydrochloric acid (pH adjuster), sodium hydroxide (pH adjuster), ethanol (solvent), purified water (solvent)

Examples 1-37 and Comparative Examples 1-7
Using the above-mentioned components, oral compositions of Examples 1 to 37 and Comparative Examples 1 to 7 were prepared by the following preparation method according to the blending ratio (parts by mass) shown in Tables 1 to 5. About the prepared oral composition, the sustainability of the active oxygen elimination effect and formulation stability were evaluated according to the following procedure. The evaluation results are shown in Tables 1-5.

(Method for preparing oral composition)
Ethanol, propylene glycol and component (A) were added to purified water and dissolved. Component (B) was added to the resulting solution. Here, ascorbic acid-2-phosphate magnesium, which is a water-soluble antioxidant substance, was directly added to the solution at room temperature. The fat-soluble antioxidant substances tocopherol acetate, astaxanthin or fucoxanthin were dissolved in an ethanol / propylene glycol mixed solution in advance and then added to the solution at room temperature. (B) After adding a component, it stirred with the stirrer which has a three-one motor and a rotary blade, and was set as the uniform liquid. The pH of the obtained uniform liquid was adjusted to the range of 6-9 using the pH adjuster (hydrochloric acid or sodium hydroxide), and the composition for oral cavity was obtained. The pH was measured using a pH meter (“HM-26S” manufactured by Toa Denpa Kogyo Co., Ltd.). The composition for oral cavity was used for various evaluations after sterilizing the filter (0.22 μm).

(Evaluation of sustainability of the active oxygen scavenging effect)
Commercially available gingival fibroblasts Gin-1 (DS Pharma Biomedical Co., Ltd.) were added at 37 ° C. with 5% CO ₂ in Dullbeco's Modified Eagle Medium (D-MEM) containing 10% fetal bovine serum (FBS). Pre-cultured under conditions. 500 μL of Gin-1 prepared to 2.5 × 10 ⁴ cells / mL was seeded in a 24-well plate and cultured for 24 hours. After removing the culture solution, each of the oral compositions prepared in Examples and Comparative Examples was added (diluted 100-fold with D-MEM containing 10% FBS) and treated with drugs for 24 hours. The control group was treated by adding the same amount of sterile water.
After the drug treatment, the medium supernatant was removed, 0.5 mL of a drug-free D-MEM medium was added, and the mixture was incubated for 12 hours while stirring (5 rpm) on a shaker (manufactured by Nippon Genetics).
After the incubation, the medium supernatant was removed, and 0.5 mL of a D-MEM medium containing no drug was added again, and the mixture was incubated for 12 hours on a shaker (manufactured by Nippon Genetics) with stirring (5 rpm).
The culture supernatant was removed and 0.4 mL of D-MEM medium (containing 10 μM CM-H2DCFDA fluorescent reagent) was added and incubated for 30 minutes.
Further, the supernatant was removed, 0.5 mL of D-MEM medium (containing 0.25 mM hydrogen peroxide; assuming active oxygen) was added, incubated for 30 minutes, and then a fluorescent plate reader (“Fluoroskan Ascent, manufactured by Labsystems). )), The fluorescence intensity was measured under the conditions of Ex / Em = 485 nm / 538 nm. Using the fluorescence intensity of the control group and the fluorescence intensity of the examples and comparative examples, the formula: (fluorescence intensity of the control group−fluorescence intensity of each example / comparative example) / (fluorescence intensity of the control group) × 100 (%) From this, the active oxygen elimination rate was calculated. Here, regarding the fluorescence intensity of the control group and the fluorescence intensity of the examples and comparative examples, the fluorescence intensity of the hydrogen peroxide-free group was subtracted from the actually measured fluorescence intensity of the control group and the fluorescence intensity of the examples and comparative examples. The value (that is, the value excluding the amount of active oxygen originally possessed by the cell for viability) was used. In addition, said evaluation test was implemented 3 times about each chemical | medical agent, the average value was computed, and the active oxygen scavenging effect was evaluated based on the following evaluation criteria.

<Evaluation criteria>
◎: Active oxygen erasure rate is 30% or more ○: Active oxygen erasure rate is 20% or more and less than 30% △: Active oxygen erasure rate is 10% or more and less than 20% ×: Active oxygen erasure rate is less than 10%

(Evaluation of formulation stability)
The compositions for oral cavity prepared in Examples and Comparative Examples were stored in a high temperature bath at 50 ° C. for 1 month. The oral composition after storage was visually confirmed, and the preparation stability (discoloration and occurrence of orientation) was evaluated based on the following evaluation criteria.

<Evaluation criteria>
A: No discoloration of the composition is observed and no orientation is generated. ○: There is almost no problem in discoloration of the composition and occurrence of orientation. Δ: There is a slight problem in discoloration of the composition and / or occurrence of orientation. : Discoloration and / or orientation of the composition occurs, which is a considerable problem.

(A) The composition for oral cavity of Comparative Examples 1-4 which does not contain a component but contains only the component (B), and the oral cavity of Comparative Examples 5-7 which does not contain the component (B) and contains only the component (A) All the compositions showed only a low active oxygen scavenging rate, and the sustainability of the active oxygen scavenging effect was insufficient.
On the other hand, the composition for oral cavity of Examples 1-37 containing a combination of the component (A) and the component (B) exhibits a high active oxygen scavenging rate, is excellent in sustainability of the active oxygen scavenging effect, and is stable in formulation. It was confirmed that it was excellent.

Claims (7)

(A) A lactam compound having an acidic group selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, and 3- (2-oxo-1-azepanyl) propanoic acid and / or an alkali metal salt thereof When,
(B) Antioxidant selected from the group consisting of ascorbic acid, ascorbic acid phosphate ester salt, vitamin E, tocopherol acetate, tocopherol nicotinate, astaxanthin, fucoxanthin, glutathione, uric acid, β-carotene, vitamin A, ubiquinol, and flavonoids The composition for oral cavity containing a substance. The composition for oral cavity of Claim 1 whose (A) component is pyrrolidone carboxylic acid and / or its alkali metal salt. The component (B) is one or more antioxidants selected from the group consisting of ascorbic acid , ascorbic acid phosphate ester salt , vitamin E , tocopherol acetate, tocopherol nicotinate , astaxanthin, and fucoxanthin. The composition for oral cavity according to 2. Component (B), ascorbic acid phosphate ester salts, as well as vitamin E, which is one or more antioxidants selected from the group consisting of tocopherol acetate and tocopherol nicotinate, according to any one of claims 1 to 3 Oral composition. The composition for oral cavity according to any one of claims 1 to 4, which is used for removing active oxygen. The composition for oral cavity of any one of Claims 1-4 which is an object for periodontal disease prevention. (A) A lactam compound having an acidic group selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, and 3- (2-oxo-1-azepanyl) propanoic acid and / or an alkali metal salt thereof When,
(B) Antioxidant selected from the group consisting of ascorbic acid, ascorbic acid phosphate ester salt, vitamin E, tocopherol acetate, tocopherol nicotinate, astaxanthin, fucoxanthin, glutathione, uric acid, β-carotene, vitamin A, ubiquinol, and flavonoids An oral active oxygen scavenger containing a substance as an active ingredient.