KR102076611B1 - Oral composition - Google Patents

Abstract

It provides a composition for oral cavity having a high periodontal disease prevention effect by eliminating the active oxygen in the cells constituting the gum for a long time. (A) a lactam compound having an acidic group selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azpanyl) propanoic acid, and / or A composition for oral cavity containing a salt and (B) an antioxidant substance.

Description

Oral composition {ORAL COMPOSITION}

The present invention relates to a composition for oral cavity.

Periodontal disease is an infection caused by a bacterium mainly composed of anaerobic gram-negative bacteria such as Azepanyl porphyromonas ginivalis, and endotoxins (such as leucotoxin) and endotoxins (liposaccharides) produced by the bacteria. Etc.), causing inflammation and tissue damage. Therefore, in order to exclude periodontal pathogenic bacteria, development of a fungicide or an antibacterial agent is in progress.

On the other hand, in vivo, neutrophils and lymphocytes infiltrate the periodontal pockets and gum tissues, phagocytosis of periodontal pathogens, and produce specific antibodies to produce immune responses that exclude these foreign bodies. In recent years, however, it has been pointed out that excessive free radicals generated during phagocytosis further damage the tissues and progress the periodontal disease. In addition, even when the periodontal pathogenic bacteria die, toxins remain, and inflammation caused by toxins continues to produce new free radicals. In addition, environmental factors such as smoking and stress have also been reported to increase free radicals.

A bactericidal agent and an antimicrobial agent are preferably "immediately effective" immediately exhibiting the effect. However, the active oxygen changes in kind by chemical reactions such as hydrogen peroxide, hydroxy radicals and super oxides, and is continuously produced as the inflammation progresses. Therefore, in addition to the "high removal effect", the removal of these reactive oxygen species is preferably "long-term persistence".

For example, when fibroblasts constituting the gums are injured by reactive oxygen species, the collagen fibers are destroyed and the cell proliferation ability is lowered. Thus, the gums retract and the periodontal disease progresses. Therefore, the development of antioxidants that remove these reactive oxygen species is in progress.

As an antioxidant, for example, ascorbic acid phosphate ester salt, which is a derivative of ascorbic acid, has a higher stability than ascorbic acid and has an effect of suppressing inflammation by eliminating excess active oxygen generated in a living body. The application technique (patent document 1) to the composition for oral cavity, such as a softening agent and a troche, the improvement technique of the mucous membrane absorption by a cationic polymer combined use (patent document 2), etc. are examined. Vitamin E and its derivatives, known as fat-soluble antioxidants, are generally used as antioxidants in foods and pharmaceuticals (Patent Document 3), and techniques for improving the retention property of hydrogel particles (Patent Document 4) and the like have been proposed. . Astaxanthin and fucoxanthin are also antioxidant substances that attract attention from the height of the effect, and are incorporated into the pharmaceutical composition (patent document 5), sunburn, reduction of spots (patent document 6), and blood intake by food intake. The technique (patent document 7) etc. which reduce the active oxygen of are proposed.

Patent Document 1: Japanese Patent Application Laid-Open No. 2-292211 Patent Document 2: Japanese Patent Application Laid-Open No. 2004-83543 Patent Document 3: Japanese Patent Application Laid-Open No. 10-53515 Patent Document 4: Japanese Patent Application Laid-Open No. 2009-196987 Patent Document 5: Japanese Patent Application Laid-Open No. 2008-1623 Patent Document 6: Japanese Patent Application Laid-Open No. 2008-239606 Patent Document 7: International Publication No. 04/052385

However, the technique of utilizing antioxidants from the viewpoint of periodontal disease prevention is still insufficient. Saliva and gingival effusion are always leaked and flowed in the oral cavity, and therefore, it is very difficult for the antioxidant to act effectively around the periodontal tissue for a long time.

In order to prolong the free radicals in the cells constituting the gums for a long time, it is important to effectively activate the antioxidant against the periodontal tissue in a situation in which a gum environmental liquid such as saliva flows. According to the dental disease fact-finding survey, it is pointed out that the periodontal disease patient is as high as 80% of the Japanese people, and development of the composition for oral cavity which enables further improvement of the periodontal disease prevention effect is desired.

This invention is made | formed in view of the said situation, and an object of this invention is to provide the composition for oral cavity which has the high periodontal disease prevention effect by eliminating active oxygen in the cell which comprises a gum for a long time.

As a result of intensive studies to achieve the above object, the present inventors have found that by using a specific lactam compound in combination with an antioxidant, the active oxygen in the gum constituent cells can be eliminated for a long time even in an environment in which saliva flow is assumed. The present inventors have found and completed the present invention.

That is, this invention provides the following [1]-[5].

[1] (A) Lactam compound having an acidic group selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azpanyl) propanoic acid, and And / or a salt thereof and (B) an oral composition containing an antioxidant substance.

[2] The composition for oral cavity according to [1], wherein (A) component is pyrrolidone carboxylic acid and / or a salt thereof.

[3] [1] or [2], wherein the component (B) is at least one antioxidant selected from the group consisting of ascorbic acid and its derivatives, vitamin E and its derivatives, astaxanthin and fucoxanthin. The composition for oral cavity as described in.

[4] The composition for oral cavity according to [1] or [2], wherein the component (B) is at least one antioxidant selected from the group consisting of ascorbic acid phosphate ester salts, vitamin E and derivatives thereof.

[5] (A) Lactam compound having an acidic group selected from the group consisting of pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid, 3- (2-oxo-1-azpanyl) propanoic acid, and And / or a salt thereof and (B) an active oxygen scavenger comprising an antioxidant as an active ingredient.

According to the present invention, it is possible to provide a composition for oral cavity having a high periodontal disease prevention effect by eliminating active oxygen in cells constituting the gum for a long time.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail based on the suitable embodiment.

[Oral composition]

The composition for oral cavity of this invention is an acid selected from the group which consists of (A) pyrrolidone carboxylic acid, 6-oxo-2- piperidine carboxylic acid, and 3- (2-oxo-1- azepanyl) propanoic acid. A lactam compound having a group and / or a salt thereof, and (B) an antioxidant.

<(A) component>

(A) component contained in the composition for oral cavity of this invention is a group which consists of pyrrolidone carboxylic acid, 6-oxo-2- piperidine carboxylic acid, and 3- (2-oxo-1- azepanyl) propanoic acid Lactam compounds having an acidic group selected from and / or salts thereof.

In the present invention, by using such (A) component in combination with an antioxidant substance of (B) component, the composition for oral cavity having a high periodontal disease prevention effect by eliminating active oxygen in the cells constituting the gum for a long time is realized. will be. That is, (A) component has the effect of improving the persistence of the intracellular active oxygen scavenging effect of an antioxidant substance.

When (A) component is a salt form, it will not specifically limit, if it is a pharmacologically acceptable salt as such salt. As a pharmacologically acceptable salt, an acid addition salt, a base addition salt, and an amino acid salt are mentioned, for example. As the specific example, Inorganic acid salts, such as hydrochloride, a hydrochloride salt, a sulfate, a hydrogen iodide salt, a nitrate salt, a phosphate salt; Organic acid salts such as citrate, oxalate, acetate, formate, propionate, benzoate, trifluoroacetate, maleate, tartarate, methanesulfonate, benzenesulfonate and paratoluenesulfonate; Inorganic base salts such as sodium salt, potassium salt, calcium salt, magnesium salt and ammonium salt; Organic base salts such as triethylammonium salt, triethanolammonium salt, pyridinium salt and diisopropylammonium salt; And amino acid salts such as arginine salts, asparagine salts and glutamate salts. Among these salts, water-soluble salts are preferable, and among them, inorganic base salts are preferable, alkali metal salts are more preferable, and sodium salts and potassium salts are particularly preferable.

From the viewpoint of enhancing the persistence 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 its salt used as (A) component can be synthesize | combined according to a well-known scheme. Or the lactam compound or its salt used as (A) component may use a commercial item.

As a commercial item of a pyrrolidone carboxylic acid, "AJIDEW A-100 (trademark)" marketed by Ajinomoto Co., Ltd. is mentioned, for example. As a commercial item of sodium pyrrolidone carbonate, "AJIDEW NL-50 (registered trademark)" marketed from Ajinomoto Co., Ltd. is mentioned, for example.

As a commercial item of 6-oxo-2-piperidine carboxylic acid, "(S) -6-Oxo-2-piperidine carboxylic acid (brand name)" sold by Sigma Aldrich Japan Co., Ltd. is mentioned, for example. .

As a commercial item of 3- (2-oxo-1-azpanyl) propanoic acid, for example, "3- (2-Oxoazepan-1-yl) propanoic acid (brand name)" released from Sigma Aldrich Japan Co., Ltd. Can be mentioned.

In the composition for oral cavity of this invention, (A) component may be used individually by 1 type, or may be used in combination of 2 or more type.

From the viewpoint of increasing the persistence of the active oxygen scavenging effect, the content of the component (A) in the composition for oral cavity of the present invention is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, and even more preferably 1% by mass or more. desirable.

It is preferable that it is 10 mass% or less from a viewpoint of the persistence of an active oxygen scavenging effect, and formulation stability, and, as for the upper limit of content of (A) component in the composition for oral cavity of this invention, it is more preferable that it is 5 mass% or less.

In one embodiment, it is preferable that content of (A) component in the composition for oral cavity of this invention is 0.1-10 mass% with respect to whole quantity of the composition for oral cavity, It is more preferable that it is 0.5-5 mass%, It is more preferable that it is 1-5 mass%.

In addition, in this invention, content of each component in the composition for oral cavity is based on the quantity 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.

As an antioxidant substance which can be used suitably as (B) component, For example, ascorbic acid and its derivative (s), vitamin E and its derivative (s), astaxanthin, fucoxanthin, glutathione, uric acid, (beta) carotene, vitamin A, ubiquinol And flavonoids. Here, ascorbic acid phosphate ester salts, such as magnesium ascorbic acid phosphate ester, and ascorbic acid phosphate ester sodium, are mentioned as a derivative of ascorbic acid. As a derivative of vitamin E, tocopherol acetate and tocopherol nicotinate are mentioned, for example.

(B) As a component, the group which consists of ascorbic acid and its derivative (s), vitamin E and its derivative (s), astaxanthin, and fucoxanthin from a viewpoint of showing the sustainability of the active oxygen scavenging effect excellent in combination with (A) component. One or more antioxidants selected from the group are preferred, and one or more antioxidants selected from the group consisting of ascorbic acid phosphate ester salts, vitamin E and its derivatives, astaxanthin, and fucoxanthin are more preferred. More preferred is at least one antioxidant selected from the group consisting of corticophosphate ester salts and vitamin E and derivatives thereof, and at least one antioxidant selected from the group consisting of ascorbic acid phosphate ester magnesium and tocopherol acetate. desirable.

The antioxidant substance used as (B) component can be synthesize | combined according to a well-known scheme. Alternatively, a commercially available product may be used for the antioxidant substance used as the component (B).

In the composition for oral cavity of this invention, (B) component may be used individually by 1 type, or may be used in combination of 2 or more type.

From the viewpoint of increasing the persistence of the active oxygen scavenging effect, the content of the component (B) in the composition for oral cavity of the present invention is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, and even more preferably 0.1% by mass or more. desirable.

It is preferable that it is 2 mass% or less from a viewpoint of formulation stability, and, as for the upper limit of content of (B) component in the composition for oral cavity of this invention, it is more preferable that it is 1 mass% or less.

In one embodiment, it is preferable that content of (B) component in the composition for oral cavity of this invention is 0.01-2 mass% with respect to whole quantity of the composition for oral cavity, It is more preferable that it is 0.05-1 mass%, It is more preferable that it is 0.1-1 mass%.

There is a preferable range in the compounding ratio of (A) component and (B) component. That is, from the viewpoint of formulation stability, in the composition for oral cavity of the present invention, the mass ratio [(A) component / (B) component] of the component (A) to the component (B) is preferably 1 or more, and preferably 2 or more. More preferred. Moreover, it is preferable that the mass ratio [(A) component / (B) component] of (A) component with respect to (B) component in the composition for oral cavity of this invention from a viewpoint of the persistence of an active oxygen scavenging effect is 100 or less. And it is more preferable that it is 30 or less. In order to make the persistence of active oxygen scavenging effect and formulation stability compatible at a high level, it is preferable that it is 1-100, and it is more preferable that it is 2-30.

The shape and formulation of the composition for oral cavity of the present invention are not particularly limited. For example, it can prepare in various shapes, such as a liquid system (liquid, liquid, paste form), a solid system (solid, solid form). Examples of the dosage form include dentifrice compositions such as soft toothpaste, liquid toothpaste, liquid toothpaste, powdered toothpaste, mouthwash composition, coating agent composition, oral pasta, dry freshener composition, and food form (e.g. chewing gum, tablets). , Candy, gummi, film, troche, etc.).

In addition to said each component, the well-known additive component (pharmacologically acceptable carrier) which can be used for the oral composition can be mix | blended with the composition for oral cavity of this invention in the range which does not impair the effect of this invention. Such additives include, for example, abrasives, caking agents, thickeners, surfactants, sweeteners, preservatives, fragrances, medicinal ingredients, colorants, varnishes, pH adjusters, solvents, excipients, and can be appropriately selected depending on the formulation. . Although the specific example of an addition 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.

As the abrasive, for example, silica-based abrasives such as silicic anhydride, crystalline silica, amorphous silica, silica gel, aluminosilicate, zeolite, calcium hydrogen phosphate anhydride, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, calcium carbonate Aluminum hydroxide, alumina, magnesium carbonate, magnesium triphosphate, zirconium silicate, tricalcium phosphate, hydroxyapatite, calcium tetraphosphate, synthetic resin-based abrasives and the like.

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

As a caking additive, for example, pullulan, gelatin, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, carrageenan, sodium alginate, xanthan rubber, sodium polyacrylate, gum arabic, guar rubber, Locust bean rubber, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer and the like. A caking additive can be used individually by 1 type or in combination of 2 or more type. The compounding quantity in the case of using a caking additive is 0.01-3 mass% normally with respect to the whole composition.

As a viscous agent (wetting agent), sorbitol, propylene glycol, butylene glycol, glycerin, polyethyleneglycol, etc. are mentioned, for example. A viscous agent can be used individually by 1 type or in combination of 2 or more type. When using a viscous agent, the compounding quantity can be determined in the range which does not prevent the effect of this invention, and is 1-60 mass% with respect to the whole composition normally.

As surfactant, anionic surfactant, a nonionic surfactant, etc. are mentioned, for example.

Examples of the anionic surfactants include N-acylamino acid salts, α-olefin sulfonate salts, N-acyl sulfonate salts, alkyl sulfate salts, sulfates of glycerin fatty acid esters, and the like. Among these, N-acylamino acid salt, (alpha)-olefin sulfonate, alkyl sulfate, etc. are preferable at the point of versatility, and lauroyl sarcosine sodium and the carbon chain of an alkyl chain from a foamability and water-resistant water resistance point As length, C10-C16 sodium-olefin sulfonate, sodium lauryl sulfate, etc. are more preferable.

Examples of nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene hardened castor oil, polyoxyethylene ethers of glycerin esters, sucrose fatty acid esters, alkylolamides, Glycerin fatty acid ester etc. are mentioned. Among them, polyoxyethylene alkyl ether, polyoxyethylene hardened castor oil, alkylolamide, sorbitan fatty acid ester and the like are suitably used in view of general versatility. It is preferable that the carbon chain length of an alkyl chain of polyoxyethylene alkyl ether is 14-18 in carbon number. It is preferable that the number of ethylene oxide average added moles of polyoxyethylene alkyl ether is 15-30. As for polyoxyethylene hardened castor oil, it is preferable that ethylene oxide average added mole number (average added EO) is 20-100. The alkylolamide preferably has a carbon chain length of 12 to 14 carbon atoms in the alkyl chain. As for sorbitan fatty acid ester, it is preferable that carbon number of a fatty acid is 12-18. It is preferable that polyoxyethylene sorbitan fatty acid ester has 16-18 carbon atoms of a fatty acid. In addition, the polyoxyethylene sorbitan fatty acid ester preferably has an average number of ethylene oxide of 10 to 40.

Surfactant can be used individually by 1 type or in combination of 2 or more type. The compounding quantity at the time of using surfactant is 0-10 mass% with respect to the whole composition normally, and it is preferable that it is 0.01-5 mass%.

Examples of the sweetening agent include sodium saccharin, stevioside, neohesperidyl hydrochalcone, glycyrrhizin, peraryllatin, p-methoxycinnamicaldehyde, taumartin, palatinose, maltitol, xylitol, and arabitol. Can be. A sweetener can be used individually by 1 type or in combination of 2 or more type. When using a sweetener, a compounding quantity can be suitably determined in the range which does not impair the effect of this invention.

As a preservative, paraoxybenzoic acid ester, such as sodium benzoate, methyl paraben, ethyl paraben, and butyl paraben, ethylenediamine tetraacetic acid salt, benzalkonium chloride, etc. are mentioned, for example. A preservative can be used individually by 1 type or in combination of 2 or more type. When using a preservative, the compounding quantity can be suitably determined in the range which does not impair the effect of this invention.

As a fragrance | flavor, a natural fragrance, a synthetic fragrance (single fragrance | flavor), a combination fragrance (oil-based fragrance (oil-based fragrance), powdered fragrance, etc.) are mentioned, for example. A fragrance | flavor can be used individually by 1 type or in combination of 2 or more type.

As natural fragrance, for example, mastic oil, parsley oil, anise oil, eucalyptus oil, winter green oil, cassia oil, menthol oil, spearmint oil, peppermint oil, lemon oil, corianda 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 absolut, rose absolut, orange flower , Citrus oil, mixed fruit oil, strawberry oil, cinnamon oil, clove oil, grape oil, thyme oil, sage oil, peppermint oil, rosemary oil, marjoram oil, oliganum oil, grapefruit oil, sweet oil, yuzu oil, Mango high pressure solution, orange flower pressure solution, pepper extract, ginger oleoresin, pepper oleoresin, capsicum oleoresin and the like.

As a single-piece fragrance, for example, carbon, anetol, methyl salicylate, cinnamic aldehyde, linalool, linalyl acetate, limonene, menton, menthyl acetate, pinene, octyl aldehyde, citral, pullegon, carbyl acetate, Anisealdehyde, ethyl acetate, ethyl butyrate, allylcyclohexanepropionate, methyl anthranilate, ethyl methyl anthranilate, vanillin, undecaractone (γ-undecalactone, δ-undecalactone, etc.), hexanal (Trans-2-hexan, etc.), ethynol alcohol propyl alcohol, butanol, isoamyl alcohol, hexenol (cis-3-hexenol, etc.), dimethylsulfide, cyclotene, furfural, trimethylpyrazine, ethyl lactate , Ethylrioacetate, cineol (1,8-cineol, etc.), eugenol, mentofuran, linalool oxide, vanillyl butyl ether, isopulegol, praneol, ethylcyclopentenolone, 2-methylbutyl Rick Acid, Propionic Acid, Decaractone (γ-dekaralactone, δ-dekaralactone, etc.), nonalactone (γ-nonalalactone, δ-nonlactone, etc.), hexalactone (γ-hexalactone, δ-hexalactone, etc.), isoamyl Acetate, benzaldehyde, hexyl acetate, ethyl-2-methylbutylate, benzyl alcohol, α-terpineol, phenylethyl glycidate, phenylethyl alcohol, allyl hexanoate, methyl cinnamate, ethylβ-methylthiopropio Nate, cis-6-nonenol, charon, methyl jasmonate, etc. are mentioned. As a single fragrance, menthol, N-ethyl-p-mentan-3-carboxyamide, N- (ethoxycarbonylmethyl) -3-p-mentane carboxyamide, N, 2,3-trimethyl-2-isopropyl Butanamide, 3- (L-methoxy) propane-1,2-diol, menthyl lactate (mentyl lactate), monomentyl succinate, mentonglycerine acetal, 3-l-menthoxypropane-1,2-diol, Menthone glycerine ether, a pilanthol, a monomentyl succinate, etc. are illustrated.

Combination fragrance is a fragrance which is produced by combining a single fragrance and / or a natural fragrance. For example, 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, etc. have.

The form of the fragrance is not limited, and any of powders which are spray dried with essential oils, extracts, solids, and any of these may be used. It is preferable to use said fragrance raw material 0.000001-1 mass% in a formulation composition. Moreover, it is preferable to use 0.1-2.0 mass% of fragrance | flavor use for fragrance | flavor using the said fragrance | flavor raw material in a formulation composition.

As a medicinal component, the following components are mentioned, for example: Bactericidal or antimicrobial agents, such as chlorohexidine, triclosan, isopropylmethylphenol, a cetylpyridinium chloride, zinc gluconate, and zinc citrate; Tartar preventive agents such as condensed phosphates and ethane hydroxy di-hosponates; Anti-inflammatory agents such as tranexamic acid, glycyrrhizin dipotassium salt, ε-aminocaproic acid and sulfur white extract; Coating agents such as hydroxyethyl cellulose dimethyl diallyl ammonium chloride; Astringents such as allantoinchlorhydroxyaluminum, vitamin C, lysozyme chloride, glycyrrhetinic acid and salts thereof, sodium chloride, allantoin and the like; Perceptual hypersensitivity inhibitors, such as strontium chloride. The compounding quantity at the time of using a medicinal component can be suitably set in the pharmaceutically acceptable range about each medicinal component.

As a coloring agent, natural colors, such as a safflower red pigment, a gardenia yellow pigment, a gardenia blue pigment, a purple pigment, a red yeast pigment, a red cabbage pigment, a carrot pigment, a hibiscus pigment, a cacao pigment, a spirulina blue pigment, a tamarind pigment, Forensic pigments such as Sona, Red No. 3, Red No. 104, Red No. 105, Red No. 106, Yellow No. 4, Yellow No. 5, Green No. 3, Blue No. 1, riboflavin, copper chloropin sodium, titanium dioxide, etc. Can be mentioned. When mix | blending a coloring agent, it is preferable that the compounding quantity is 0.00001-3 mass% with respect to the whole composition.

As a brightening agent, waxes, such as shellac, carnauba wax, and candelilla nap, calcium stearate, etc. are mentioned, for example. When mix | blending a brightening agent, the compounding quantity is 0.01-5 mass% with respect to the whole composition.

PH (20 degreeC) of the composition for oral cavity of this invention is 6-10 normally, Preferably it is 6-9. Examples of the pH regulator 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, sodium citrate, sodium hydrogen citrate, and phosphoric acid. Acids, such as sodium and sodium dihydrogen phosphate, an alkali, and a buffer are mentioned. When mix | blending a pH adjuster, the compounding quantity can be suitably determined in the range which does not impair the effect of this invention.

Examples of the solvent include water and lower alcohols having 3 or less carbon atoms such as ethanol and propanol. A solvent is mix | blended normally with the liquid composition for oral cavity. When mix | blending water as a solvent, it is preferable that the compounding quantity is 20-95 mass% with respect to the whole composition. When mix | blending lower alcohol as a solvent, it is preferable that the compounding quantity is 1-20 mass% with respect to the whole composition.

Examples of the excipient include starch syrup, glucose, fructose, invert sugar, dextrin, oligosaccharide, and the like. When the composition for oral cavity is a food preparation, an excipient is mix | blended normally. When mix | blending an excipient, the compounding quantity can be suitably determined in the range which does not impair the effect of this invention.

[Active Oxygen Scavenger]

The active oxygen scavenger of the present invention is selected from the group consisting of (A) pyrrolidonecarboxylic acid, 6-oxo-2-piperidinecarboxylic acid and 3- (2-oxo-1-azpanyl) propanoic acid The lactam compound which has an acidic group, and / or its salt, and (B) antioxidant substance are included as an active ingredient.

The compounding ratio of (A) component and (B) component in the active oxygen scavenger of this invention can be made the same as the compounding ratio demonstrated in said [oral composition].

The active oxygen targeted by the active oxygen scavenger of the present invention is not particularly limited. Among them, the active oxygen scavenging agent of the present invention is excellent in the persistence of the active oxygen scavenging effect even in an environment in which gum environmental liquids such as saliva flow, and is preferably used for removing the active oxygen in the gum constituent cells.

The dosage form of the active oxygen scavenger of the present invention is not particularly limited, for example, oral administration (eg, oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration). , Transdermal administration, nasal administration, transpulmonary administration, and the like). Among these, the dosage form with less invasiveness is preferable, and it is more preferable that it is oral administration or transdermal administration.

The subject of ingestion of the active oxygen scavenger of the present invention is a subject who already develops symptoms (for example, gum retraction) of the periodontal tissues and wishes to improve them. Target person who does not do it but wants to prevent is mentioned. The administration timing of the agent of the present invention is not particularly limited.

Example

Hereinafter, the present invention will be described in detail by way of examples. Examples 1 to 37 and Comparative Examples 1 to 7 described below are for properly explaining the present invention, and the present invention is not limited to the examples described below.

The main raw materials used for Examples 1 to 37 and Comparative Examples 1 to 7 described below are collectively described below.

[Main Raw Material Used in Examples and Comparative Examples]

<(A) component>

(A-1): pyrrolidone carboxylic acid

Ajinomoto Co., Ltd., "AJIDEW A-100" (registered trademark)

(A-2): 6-oxo-2-piperidine carboxylic acid

Sigma Aldrich Japan Co., Ltd., a brand name "(S) -6-Oxo-2-piperidine carboxylic acid"

(A-3): 3- (2-oxo-1-azpanyl) propanoic acid

Sigma Aldrich Japan Co., Ltd., a brand name "3- (2-Oxoazepan-1-yl) propanoic acid"

<(B) component>

(B-1): Ascorbic acid-2-phosphate ester magnesium

Product made in Showa Electric Works, brand name "ascorbic acid PM"

(B-2): tocopherol acetate

A product made by DSM Neutorishon Japan, a brand name "Tocopherol acetate ester"

(B-3): Astaxanthin

Wakojunyaku Co., Ltd., grade "for cell biology"

(B-4): fucoxanthin

Wakojunyaku Co., Ltd., grade "for cell biology"

<Other ingredients added>

Propylene glycol (viscosity agent), hydrochloric acid (pH regulator), sodium hydroxide (pH regulator), ethanol (solvent), purified water (solvent)

Examples 1 to 37 and Comparative Examples 1 to 7

The composition for oral cavity of Examples 1-37 and Comparative Examples 1-7 was prepared by the following preparation method according to the compounding ratio (mass part) shown in Tables 1-5 using the above-mentioned component. About the prepared oral composition, the persistence and formulation stability of the active oxygen scavenging effect were evaluated in the following procedure. The evaluation results are shown in Tables 1 to 5.

(Preparation method of composition for oral cavity)

To purified water, ethanol, propylene glycol and (A) component were added and dissolved. (B) component was added to the obtained solution. Here, ascorbic acid-2-phosphate ester magnesium, which is a water-soluble antioxidant, was added to the solution as it was at room temperature. Tocopherol acetate, astaxanthin or fucoxanthin, which are fat-soluble antioxidants, were previously dissolved in an ethanol / propylene glycol mixture and added to the solution at room temperature. After adding (B) component, it stirred with the stirrer which has a three-one motor and a rotary blade, and made it the homogeneous liquid. The pH of the obtained homogeneous liquid was adjusted to the range of 6-9 using a pH adjuster (hydrochloric acid or sodium hydroxide), and the composition for oral cavity was obtained. The measurement of pH was performed using the pH meter ("HM-26S" by Doa Electric Industry Co., Ltd.). The composition for oral cavity was used for various evaluation, after sterilizing a filter (0.22 micrometer).

(Evaluation of Persistence of Active Oxygen Scavenging Effect)

Commercially available gum fibroblasts Gin-1 (manufactured by DS Pharma Biomedical Co., Ltd.) in Dullbecco's Modified Eagle Medium (D-MEM) containing 10% fetal bovine serum (FBS) at 37 ° C and 5% CO Preculture was carried out under the conditions of ₂ . 500 μl of Gin-1 prepared at 2.5 × 10 ⁴ cells / ml was seeded in a 24-well plate and incubated for 24 hours. After removing the culture solution, the oral compositions prepared in Examples and Comparative Examples were each added (100-fold dilution with D-MEM containing 10% FBS), and drug treatment was performed for 24 hours. In addition, the control group was treated with the same amount of sterile water.

After the drug treatment, the medium supernatant was removed, 0.5 mL of D-MEM medium containing no drug was added, and incubated for 12 hours with stirring (5 rpm) in a shaker (manufactured by Nippon Genetics).

After the incubation, the medium supernatant was removed, and 0.5 ml of D-MEM medium containing no drug was added again, and incubated for 12 hours while stirring (5 rpm) on a shaker (manufactured by Nippon Genetics Co., Ltd.).

The medium supernatant was removed, 0.4 ml of D-MEM medium (containing 10 µm CM-H2 DCFDA fluorescent reagent) was added and incubated for 30 minutes.

The supernatant was again removed, 0.5 ml of D-MEM medium (containing 0.25 mM hydrogen peroxide; assumed active oxygen) was incubated for 30 minutes, and then a fluorescent plate reader (Fluoroskan Ascent, manufactured by Labsystems) was used. , The fluorescence intensity was measured under the condition 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 and comparative example) / (fluorescence intensity of the control group) × 100 (%) The active oxygen scavenging ratio was calculated from Here, the fluorescence intensity of the control group and the fluorescence intensity of the examples and the comparative examples are obtained by subtracting the fluorescence intensity of the hydrogen peroxide-free group from the measured fluorescence intensity and the fluorescence intensity of the examples and the comparative examples (that is, Value except for the amount of free radicals originally possessed by the cells for survival activity). Moreover, the said evaluation test was performed 3 times about each drug, and the average value was computed, and the active oxygen scavenging effect was evaluated based on the following evaluation criteria.

<Evaluation Criteria>

◎: reactive oxygen scavenging rate is more than 30%

○: free radical scavenging rate is 20% or more but less than 30%

(Triangle | delta): 10% or more and less than 20% of active oxygen clearance

X: active oxygen scavenging rate is less than 10%

(Evaluation of formulation stability)

The composition for oral cavity prepared by the Example and the comparative example was preserve | saved for 1 month in 50 degreeC high temperature tank. The composition for oral cavity after storage was visually confirmed, and formulation stability (discoloration and sediment development) was evaluated based on the following evaluation criteria.

<Evaluation Criteria>

(Double-circle): Discoloration of a composition is not recognized, and sediment does not generate | occur | produce, either.

(Circle): There is almost no problem in discoloration of a composition and generation of sediment.

(Triangle | delta): There is a problem with generation | occurrence | production of discoloration and / or sediment of a composition.

X: Discoloration and / or sediment generate | occur | produce a composition, and there exists a problem considerably.

The composition for oral cavity of Comparative Examples 1-4 containing only (B) component without containing (A) component, and the composition for oral cavity of Comparative Examples 5-7 containing only (A) component without containing (B) component. In all, only the low active oxygen scavenging ratio was shown, and the sustainability of the active oxygen scavenging effect was insufficient.

On the other hand, the composition for oral cavity of Examples 1-37 which combines (A) component and (B) component shows high active oxygen scavenging rate, is excellent in the persistence of an active oxygen scavenging effect, and excellent also in formulation stability. It was confirmed.

Claims (9)

(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-azpanyl) propanoic acid and / or With alkali metal salts,
(B) for oral cavity, characterized in that it contains at least one antioxidant substance selected from the group consisting of ascorbic acid, ascorbic acid phosphate ester salt, vitamin E, tocopherol acetate, nicotinic acid tocopherol, astaxanthin and fucoxanthin. Composition. The method of claim 1,
(A) Component is pyrrolidone carboxylic acid and / or its alkali metal salt, The composition for oral cavity characterized by the above-mentioned. The method according to claim 1 or 2,
Content of (A) component is 0.1 mass% or more and 10 mass% or less, The composition for oral cavity characterized by the above-mentioned. The method according to claim 1 or 2,
(B) The composition for oral cavity characterized by the at least 1 type of antioxidant substance selected from the group which consists of ascorbic acid phosphate ester salt and vitamin E, tocopherol acetate, and nicotinic acid tocopherol. The method according to claim 1 or 2,
Content of (B) component is 0.01 mass% or more and 2 mass% or less, The composition for oral cavity characterized by the above-mentioned. The method according to claim 1 or 2,
The mass ratio of (A) / (B) is 1 or more and 100 or less, The composition for oral cavity characterized by the above-mentioned. The method according to claim 1 or 2,
Oral composition, characterized in that for removing the active oxygen. The method according to claim 1 or 2,
Oral composition, characterized in that for preventing periodontal disease. (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-azpanyl) propanoic acid and / or With alkali metal salts,
(B) selected from the group consisting of ascorbic acid, ascorbic acid phosphate ester salt, vitamin E, tocopherol acetate, nicotinic acid tocopherol, astaxanthin, fucoxanthin, glutathione, uric acid, β-carotene, vitamin A, ubiquinol and flavonoids Oral oxygen scavenging composition comprising an antioxidant substance as an active ingredient.