WO2014125977A1

WO2014125977A1 - Oral composition

Info

Publication number: WO2014125977A1
Application number: PCT/JP2014/052676
Authority: WO
Inventors: 眞里阿部; 貴士近澤; 苗穂鈴木
Original assignee: ライオン株式会社
Priority date: 2013-02-14
Filing date: 2014-02-05
Publication date: 2014-08-21
Also published as: CN104994835B; KR20150118144A; CN104994835A; JP6222217B2; JPWO2014125977A1

Abstract

Provided is an oral composition which has an excellent bactericidal effect against oral bacteria, in particular, porphyromonas gingivalis, a periodontal disease-causing bacteria, and has an excellent cytotoxicity inhibitory effect in the oral cavity, which is effective in the prevention and treatment of peridontal disease, and which contains (A) human defensin and (B) ascorbic acid ester or a salt thereof.

Description

Oral composition

The present invention has an excellent bactericidal effect against oral bacteria, particularly porphyromonas gingivalis, a periodontal disease-causing bacterium, and an oral cytostatic effect, and is effective in preventing and treating periodontal disease. The present invention relates to an oral composition.

Periodontal disease is an infection caused by bacteria, mainly anaerobic gram-negative bacteria such as Porphyromonas gingivalis, and exotoxins (such as leukotoxin) and endotoxins (such as lipopolysaccharide) produced by the bacteria. ) Induces inflammation and damages the tissue. On the other hand, in the living body, neutrophils and lymphocytes infiltrate the periodontal pockets and gingival tissues, phagocytosing bacteria, and creating an immune response that eliminates these foreign substances by creating specific antibodies, In recent years, it has been pointed out that active oxygen generated excessively during phagocytosis further damages biological tissues. For example, when fibroblasts constituting the gingiva are injured by active oxygen, collagen fibers are destroyed and the cell growth ability is reduced, so that the gingiva is retracted and periodontal disease progresses.
Therefore, for the prevention and treatment of periodontal diseases such as periodontitis, it is considered effective to suppress oral cavity cell damage as described above in addition to sterilization of periodontal disease-causing bacteria in the oral cavity. Therefore, development of a technique for providing an oral composition having both effects is desired.

Regarding sterilization of periodontopathic bacteria in the oral cavity, human defensin, a host-derived peptide, is known to have antibacterial action against a wide range of oral pathogenic bacteria and is safe for the human body. In Patent Document 1 (Japanese Patent Laid-Open No. 2001-288105), human β-defensin has a strong antibacterial activity against a periodontitis-causing fungus, Actinobacillus actinomycetemcomitans, and Porphyromonas gingivalis It is disclosed that periodontitis-causing bacteria such as (Porphyromonas gingivalis) also have antibacterial activity, and a human β-defensin-containing dentifrice has been proposed. Patent Document 2 (Japanese Patent Laid-Open No. 2009-155214) proposes a composition for oral cavity in which the antibacterial effect of oral biofilm is improved by using human defensin and dextranase in combination.
However, human defensins cannot be said to have a sufficient bactericidal effect on periodontopathic bacteria, and improvement of bactericidal power has been a problem.

On the other hand, as for the inhibition of oral cell damage, ascorbic acid esters such as ascorbic acid phosphates or salts thereof eliminate excess active oxygen produced in the living body and protect the living tissue from oxidative stress injury. Although it is known that it suppresses inflammation and has an effect of inhibiting the damage of oral cells, the effect of inhibiting the cytotoxicity still has room for improvement. In addition, ascorbic acid ester or a salt thereof does not have a bactericidal effect on periodontal disease-causing bacteria.

JP 2001-288105 A JP 2009-155214 A

The present invention has been made in view of the above circumstances, and has an excellent bactericidal effect against oral bacteria, especially periodontal disease-causing bacteria and oral cell injury-suppressing effect, and is effective for the prevention and treatment of periodontal disease. The purpose is to provide goods.

As a result of intensive studies to achieve the above object, the present inventors have found that when (A) human defensin and (B) ascorbic acid ester or a salt thereof are used in combination, oral bacteria, particularly periodontal disease-causing bacteria. It was found that the bactericidal effect and the oral cell injury-suppressing effect on a certain Porphyromonas gingivalis (hereinafter abbreviated as Pg bacteria) are remarkably improved.

That is, human defensin, which is a peptide derived from the host, has antibacterial activity against periodontal disease-causing bacteria and is known as a safe component to the human body. However, when the present inventors examined its bactericidal effect, P. of periodontal disease-causing bacteria g. It was found that there is a problem that there is not enough bactericidal effect against bacteria. Therefore, as a result of further study to solve this problem, combining (A) human defensin and (B) ascorbic acid ester or a salt thereof, particularly ascorbic acid phosphate, ascorbic acid sulfate or a salt thereof, Surprisingly, the components (A) and (B) act specifically and synergistically to enhance the bactericidal effect of oral defensin-derived oral bacteria, particularly the bactericidal effect on the above-mentioned periodontal disease-causing bacteria, and ascorbic acid esters Alternatively, the present inventors have found that the cytotoxicity-inhibiting effect by suppressing oxidative stress derived from the salt thereof is enhanced, and the oral bacteria killing effect and cytotoxicity-inhibiting effect are excellent. Furthermore, by incorporating a combination system of the components (A) and (B) into the oral composition, a preparation that exhibits high oral bactericidal and bactericidal effects and is effective in preventing and treating periodontal disease. I was able to get it.

In this case, as shown in the comparative examples described later, the oral bacterial bactericidal effect of human defensin is not sufficient, the cytotoxicity-inhibiting effect is not observed, and the cytotoxicity-inhibiting effect of ascorbic acid ester or its salt is not sufficient. In addition, although the bactericidal effect on oral bacteria is not recognized, as shown in the examples, in the present invention, the combination system of (A) and (B), It was able to enhance the bactericidal effect of oral bacteria and the effect of suppressing cytotoxicity beyond the additive effect of the single compound system. In addition, the above-described effects of the present invention are specific to the combined system of the components (A) and (B), and the histatin of salivary protein having antibacterial activity is used in place of the component (A). Or ascorbate such as sodium ascorbate cannot be used in place of the component (B), and is particularly remarkable.

Accordingly, the present invention provides the following oral composition.
[1]
An oral composition comprising (A) human defensin and (B) an ascorbic acid ester or a salt thereof.
[2]
The composition for oral cavity according to [1], wherein the component (A) is human defensin β-2 or human defensin β-3.
[3]
(B) The composition for oral cavity as described in [1] or [2] whose component is 1 or more types chosen from ascorbic-acid phosphate and its salt, ascorbic-acid sulfate, and its salt.
[4]
The composition for oral cavity according to [3], wherein the component (B) is magnesium ascorbate phosphate and / or sodium ascorbate phosphate.
[5]
The oral composition according to any one of [1] to [4], which comprises 0.000005 to 0.0005 mass% of component (A) and 0.1 to 2 mass% of component (B).
[6]
The oral composition according to any one of [1] to [5], wherein the component (B) is 200 to 400,000 times the mass of the component (A).
[7]
The oral composition according to any one of [1] to [6], which is a dentifrice or mouthwash.
[8]
The oral composition according to any one of [1] to [7], which is used for prevention or treatment of periodontal disease.

According to the present invention, oral bacteria, particularly P. g. It is possible to provide a composition for oral cavity containing human defensin which is excellent in bactericidal effect against bacteria and suppressive effect on cell damage in the oral cavity, is safe for the human body, and is effective for prevention and treatment of periodontal disease.

Hereinafter, the present invention will be described in further detail. The composition for oral cavity of the present invention is characterized in that (A) human defensin and (B) ascorbic acid ester or a salt thereof are used in combination. The effect and the cytotoxic effect are improved.

(A) Human defensin includes human defensin α, human defensin β-1, human defensin β-2, and human defensin β-3, and one or more types selected from these are used. However, human defensin β-2 and human defensin β-3 are particularly preferable in terms of the bactericidal effect of periodontal disease-causing bacteria.
A commercially available human defensin can be used, and examples thereof include human defensin β-2 manufactured by Peptide Institute, and human defensin β-3 manufactured by Anygen.

(A) The blending amount of human defensin is preferably 0.000005 to 0.0005% (mass%, the same applies hereinafter) of the whole composition, and more preferably 0.00005 to 0.0005%. As the blending amount increases, the bactericidal effect on oral bacteria and the effect of inhibiting cell damage are improved, and blending 0.000005% or more is suitable for effect expression. In addition, if the amount is too large, not only can the effect not be improved any longer, but there may be a case where the taste is lowered and the feeling of use may be lowered, and 0.0005% or less is suitable for securing a good feeling of use. It is.

Ascorbic acid ester of component (B), one or more of hydroxyl groups at any of positions 2, 3, 5, and 6 of ascorbic acid is phosphoric acid, polyphosphoric acid, sulfuric acid, fatty acid, or other pharmaceutically acceptable. This is an ester of a compound.
As the ascorbic acid ester or a salt thereof, an ascorbic acid phosphate or a salt thereof, or an ascorbic acid sulfate or a salt thereof is particularly preferable. Ascorbic acid phosphoric acid ester and ascorbic acid sulfuric acid ester are phosphoric acid compounds such as phosphoric acid and polyphosphoric acid, or an ester of sulfuric acid. Specifically, ascorbic acid-2-phosphate, ascorbic acid-3-phosphate, ascorbic acid-6-phosphate, ascorbic acid-2-polyphosphate, ascorbic acid -2-Sulfate ester. Examples of the salt include alkali metal salts such as sodium salt, potassium salt, calcium salt, and magnesium salt, and alkaline earth metal salts. As the component (B), one or more selected from these can be used. Particularly, it is used for the oral cavity, and is an ascorbic acid phosphate ester from the viewpoint of a gingivitis preventing effect, particularly a cytotoxicity suppressing effect. The magnesium salt and sodium salt are preferably used.

(B) The amount of ascorbic acid ester or salt thereof is preferably 0.1 to 2%, more preferably 0.2 to 1% of the total composition. As the amount is increased, the bactericidal effect on oral bacteria and the effect of suppressing cytotoxicity are improved, and it is preferable to add 0.1% or more to improve the oral bacterial sterilizing effect and the effect of suppressing cytotoxicity. Moreover, 2% or less is suitable for improving the bactericidal effect of oral bacteria and ensuring a good feeling of use. If too much is added, the bactericidal effect of oral bacteria may be reduced. Moreover, a nasty taste may appear and a feeling of use may be reduced.

In the present invention, (A) ascorbic acid ester or a salt thereof (B) is preferably 20 times or more, particularly 200 to 400,000 times, more preferably 400 to 400 times by mass with respect to human defensin. 200,000 times the amount, more preferably 1,000 to 100,000 times the amount, and particularly preferably 1,000 to 10,000 times the amount. When blended in such a ratio, the effect of the present invention is further improved. To do.

The oral composition of the present invention can be produced by adopting conventional methods for various dosage forms such as toothpaste, toothpaste such as toothpaste, liquid toothpaste, liquid toothpaste, and toothpaste, and mouthwash. Especially suitable for dentifrice. In this case, depending on the purpose of the composition, the dosage form, and the like, appropriate known components can be blended in addition to the above components as long as the effects of the present invention are not hindered. For example, dentifrices contain abrasives, thickeners, binders, surfactants, and if necessary, flavors, sweeteners, colorants, preservatives, active ingredients, and the like.

As abrasives, silica-based abrasives such as silica gel, precipitated silica, aluminosilicate, zirconosilicate, dicalcium phosphate dihydrate and anhydrous, tricalcium phosphate, tetracalcium phosphate, calcium pyrophosphate, calcium carbonate, water Examples thereof include aluminum oxide, alumina, magnesium carbonate, tribasic magnesium phosphate, zeolite, hydroxyapatite, and synthetic resin abrasive. The blending amount of the abrasive is adjusted depending on the dosage form, and is preferably 2 to 40%, particularly 10 to 30% for toothpaste, and 0% for liquid toothpaste.

Examples of the thickener include sugar alcohols such as sorbit, xylit, malt, and lactite, and polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol. The blending amount is usually 5 to 50%, particularly 20 to 45%. preferable.

Examples of the binder include cellulose derivatives such as sodium carboxymethyl cellulose, methyl cellulose, and hydroxyethyl cellulose, gums such as xanthan gum and gum arabic, organic binders such as carrageenan, polyvinyl alcohol, and sodium polyacrylate, gelling silica, gel Inorganic binders such as curable aluminum silica, bee gum, and laponite. The blending amount is usually 0.1 to 5% for toothpaste and 0 to 5% for liquid toothpaste and mouthwash.

As the surfactant, an anionic surfactant, a nonionic surfactant, a cationic surfactant, and an amphoteric surfactant can be blended.
Examples of the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate, N-acyl sarcosine salts such as N-lauroyl sarcosine sodium and N-myristoyl sarcosine sodium, N-acyl glutamates such as sodium N-palmitoyl glutamate, Examples include sodium N-methyl-N-acyl taurine, sodium N-methyl-N-acylalanine, sodium α-olefin sulfonate, and the like.
Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters and maltose fatty acid esters, sugar alcohol fatty acid esters such as maltitol fatty acid esters and lactitol fatty acid esters, sorbitan fatty acid esters, glycerin fatty acid esters, hexaglyceryl monolaurate, Polyglycerin fatty acid esters such as hexaglyceryl monomyristate, decaglyceryl monolaurate, decaglyceryl monomyristic acid, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monostearate, polyoxyethylene Polyoxyethylene fatty acid esters such as hydrogenated castor oil and polyoxyethylene higher alcohols such as polyoxyethylene lauryl ether Ethers, fatty acid alkanolamides, such as lauric acid diethanolamide, polyoxyethylene polyoxypropylene copolymers, polyoxyethylene polyoxypropylene fatty acid esters.
Examples of the cationic surfactant include alkyl ammonium and alkyl benzyl ammonium salts, and examples of the amphoteric surfactant include betaines such as alkyl betaines, fatty acid amidopropyl betaines, and alkyl imidazolinium betaines.
The blending amount of the surfactant is preferably 0.001 to 10%, particularly preferably 0.1 to 5% of the entire composition.

Perfumes include peppermint oil, spearmint oil, anise oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, Lime oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie Natural fragrances such as oil, coconut oil, Iris concrete, absolute peppermint, absolute rose, orange flower, and processing of these natural fragrances (front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, Powdered fragrance etc.) and menthol Carvone, Anethole, Cineol, Methyl salicylate, Synamic aldehyde, Eugenol, 3-l-Mentoxypropane-1,2-diol, Thymol, Linalol, Linarel acetate, Limonene, Menthone, Menthyl acetate, N-Substituted-paramenthane 3-carboxamide, pinene, octylaldehyde, citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allylcyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, Hexanal, butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cycloten, furfural, trimethylpyrazine, ethyl lactate, ethyl Oral compositions such as single flavors such as thioacetate, and other flavors such as strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, tropical fruit flavor, etc. It can be used in combination with known perfume materials used in the above.
Further, the blending amount is not particularly limited, but the above fragrance material is preferably used at 0.000001 to 1% in the preparation composition. Further, as the flavoring fragrance using the fragrance material, it is preferable to use 0.1 to 2% in the preparation composition.

Examples of the sweetener include saccharin sodium, stevioside, paramethoxycinnamic aldehyde, perilartin and the like. Examples of the colorant include blue No. 1, yellow No. 4, titanium dioxide and the like.
Examples of the preservative include benzoic acid such as paraoxybenzoic acid ester and sodium benzoate, or a salt thereof.

Active ingredients include those other than human defensin and ascorbic acid esters and salts thereof, for example, nonionic fungicides such as isopropylmethylphenol, cationic fungicides such as cetylpyridinium chloride, chlorhexidine hydrochloride, benzalkonium chloride, and benzethonium chloride , Tranexamic acid, epsilon aminocaproic acid, allantoin, glycyrrhetinic acid, glycyrrhizic acid and other anti-inflammatory agents, dextranase, mutanase, amylase, protease and other enzymes, sodium fluoride, sodium monofluorophosphate fluoride, positive phosphorus Water-soluble phosphate compounds such as potassium salts of sodium and sodium salts, copper compounds such as copper gluconate and copper chlorophyllin sodium, sodium chloride, potassium nitrate, aluminum lactate, zinc chloride, zinc citrate, Inorganic salts such as strontium fluoride, vitamins such as tocopherol acetate, zeolites, azulene, dihydrocholesterol, chlorophyll, soft extract of thyme, thyme, ogon, clove, hamamelis and other plant extracts, anticalculus agent, anti-plaque agent Can be mentioned. These active ingredients can be blended in an effective amount as long as the effects of the present invention are not hindered.

Hereinafter, although an Example, a comparative example, and a formulation example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, “%” means “% by mass” unless otherwise specified.

[Examples and Comparative Examples]
A sample solution having the composition shown in Table 1 was prepared by a conventional method, and the cytotoxicity-inhibiting effect and the oral bacterial bactericidal effect were evaluated by the methods shown in the following experimental examples. The results are shown in the table.

<Experimental Example 1> Cytotoxicity inhibitory effect test A commercially available gingival fibroblast Gin-1 (manufactured by DS Pharma Biomedical Co., Ltd.) was used in a 10% fetal bovine serum (FBS) -containing Dulbecco's Modified Eagle Medium (D-MEM). And 37 ° C. and 5% CO ₂ . 400 μL of Gin-1 prepared to 5 × 10 ⁴ cells / mL was seeded in a 48-well plate and further cultured for 24 hours. After removing the culture solution, 400 μL of each sample solution shown in the table was added (diluted 20-fold with D-MEM containing 10% FBS) and treated with drugs for 48 hours.
After the treatment was completed, a 1 mM hydrogen peroxide aqueous solution (assuming active oxygen) was added for 60 minutes. After completion of the treatment, the sample solution was removed, and 400 μL of a solution containing 1 mM hydrogen peroxide (D-MEM containing 10% FBS) was added and treated for 60 minutes. After removing the solution, 200 μL of a cell activity reagent (Calcinin AM; manufactured by Invitrogen) was added and incubated at 37 ° C. under 5% CO ₂ for 30 minutes. Thereafter, the fluorescence intensity was measured under conditions of Ex / Em = 485 nm / 538 nm using a plate reader (Fluoroskan Ascent; manufactured by Labsystems).
The result calculated from the following formula (1) was taken as the cytotoxicity inhibition rate. Cytotoxicity inhibition test was performed at n = 10. The average value was calculated, and the cytotoxicity-inhibiting effect was evaluated based on the following criteria.
Cytotoxicity inhibition rate (%) = (fluorescence intensity when treated with hydrogen peroxide after treatment with sample solution) / (fluorescence intensity when treated with no hydrogen peroxide after treatment with sample solution) × 100 (1)

Criteria for evaluation of cytostatic effect;
A: Cytotoxicity inhibition rate is 90% or more. O: Cytotoxicity inhibition rate is 70% or more and less than 90%. Δ: Cytotoxicity inhibition rate is 50% or more and less than 70%. X: Cytotoxicity inhibition rate is less than 50%.

<Experimental example 2> Oral bacteria bactericidal effect test Todd Hewitt broth added with hemin (manufactured by Wako Pure Chemical Industries, Ltd., 500 μg / mL) and menadione (manufactured by Wako Pure Chemical Industries, Ltd., 100 μg / mL) A suspension of fungi was prepared from Porphyromonas gingivalis strain ATCC33277 pre-cultured with Nippon Becton Dickinson Co., Ltd. at 1 × 10 ⁹ cells / mL with physiological saline. The bacterial solution and the sample solution shown in the table were mixed at 1: 1 (volume ratio) and allowed to stand for 3 minutes. Thereafter, the solution was diluted 10-fold with physiological saline four times and smeared on a blood agar plate using a spiral plater. As a control, a mixture of physiological saline and bacterial solution at 1: 1 (volume ratio) instead of the drug was used.
The blood plate was cultured at 37 ° C. under anaerobic conditions (95 vol% nitrogen, 5 vol% carbon dioxide) for 5 days, and the number of colonies formed was counted. This oral bacteria sterilization test was conducted with n = 5. The average value was calculated, the number of colonies in the sample solution relative to the number of colonies in the control solution was determined as the viable cell rate, and the bactericidal effect in the oral cavity was evaluated based on the following criteria.

Evaluation criteria for bactericidal effect in oral cavity;
A: The viable cell rate is less than 10% compared to the control. A: The viable cell rate is 10% to less than 40% compared to the control. B: The viable cell rate is 40% to less than 80% compared to the control. More than 80% viable bacteria compared to control

Details of the raw materials used are shown below.
(A) Human defensin (Human defensin β-2, manufactured by Peptide Institute, Inc.)
(B) Ascorbic acid-2-phosphate magnesium (manufactured by Wako Pure Chemical Industries, Ltd.)
(B) Sodium ascorbate-2-phosphate (manufactured by Wako Pure Chemical Industries, Ltd.)
(B) Sodium ascorbyl-2-sulfate (manufactured by Wako Pure Chemical Industries, Ltd.)
Sodium ascorbate (manufactured by Wako Pure Chemical Industries, Ltd.)
Histatin 5 (manufactured by Wako Pure Chemical Industries, Ltd.)

The following are examples of prescriptions. All of the following examples had excellent cytotoxic effect and oral bactericidal effect.

[Prescription Example 1] Toothpaste (A) Human defensin β-2 (Peptide Institute, Inc.) 0.00001%
(B) Magnesium ascorbyl 2-phosphate ester (manufactured by Wako Pure Chemical Industries, Ltd.) 0.5
Silicic anhydride 20.0
Sodium lauryl sulfate 1.0
Propylene glycol 3.0
Sorbit liquid (100% product) 30.0
Xanthan gum 1.0
Saccharin sodium 0.1
Fragrance 1.0
Purified water balance <br/> Total 100.0%

[Prescription Example 2] Liquid dentifrice (A) Human defensin β-3 (Anygen) 0.0005%
(B) Magnesium ascorbyl 2-phosphate ester (manufactured by Wako Pure Chemical Industries, Ltd.) 0.5
Xylitol 3.0
Glycerin (AI = 100) 2.0
Polyoxyethylene (60) hydrogenated castor oil (HCO-60) 0.5
Sodium citrate 0.3
Citric acid 0.1
Sodium benzoate 0.3
Methyl benzoate 0.1
Fragrance 0.2
Saccharin sodium 0.002
Propylene glycol 3.0
Polyethylene glycol 5.0
Purified water balance <br/> Total 100.0%

[Prescription Example 3] Liquid Dentifrice (A) Human Defensin β-2 (Peptide Institute, Inc.) 0.0001%
(B) Magnesium ascorbyl 2-phosphate ester (manufactured by Wako Pure Chemical Industries, Ltd.) 0.5
Xylitol 3.0
Glycerin (100% product) 5.0
Polyoxyethylene (60) hydrogenated castor oil (HCO-60) 0.5
Sodium citrate 0.3
Citric acid 0.1
Fragrance 0.2
Ethanol 8.0
Propylene glycol 3.0
Purified water balance <br/> Total 100.0%

Claims

An oral composition comprising (A) human defensin and (B) ascorbic acid ester or a salt thereof.
The composition for oral cavity according to claim 1, wherein the component (A) is human defensin β-2 or human defensin β-3.
The composition for oral cavity according to claim 1 or 2, wherein the component (B) is at least one selected from ascorbic acid phosphate and salts thereof, ascorbic acid sulfate and salts thereof.
The composition for oral cavity according to claim 3, wherein the component (B) is magnesium ascorbate phosphate and / or sodium ascorbate phosphate.
The composition for oral cavity according to any one of claims 1 to 4, comprising 0.000005 to 0.0005 mass% of component (A) and 0.1 to 2 mass% of component (B).
The composition for oral cavity according to any one of claims 1 to 5, wherein the component (B) is 200 to 400,000 times the mass ratio of the component (A).
The composition for oral cavity according to any one of claims 1 to 6, which is a dentifrice or a mouthwash.
The composition for oral cavity according to any one of claims 1 to 7, which is used for prevention or treatment of periodontal disease.