JP5600932B2 - Plaque formation inhibitor - Google Patents

Description

The present invention relates to a plaque formation inhibitor that is excellent in bactericidal or bacteriostatic effects of pathogenic bacteria in the oral cavity and is effective in suppressing or preventing plaque formation .

  The cause of oral diseases such as dental caries, periodontal disease, and bad breath is thought to be due to various bacteria in dental plaque, and caries is streptococcus such as Streptococcus mutans (S. mutans), periodontal disease is It is a bacterial infection mainly consisting of obligate anaerobic gram-negative bacilli such as P. gingivalis, and oral bacteria such as Fusobacterium nucleatum are involved as the cause of bad breath. Yes. Therefore, it is said that it is useful to suppress plaque, that is, to sterilize or bacterize pathogenic bacteria in the oral cavity as an effective means for prevention and improvement of oral diseases.

  To date, many bactericides such as cetylpyridinium chloride, chlorhexidine, benzethonium chloride, benzalkonium chloride, depotassium chloride, and nonionic bactericides such as isopropylmethylphenol and triclosan have been used as oral germicides. It is conventionally known that it is blended into a composition for use and is effective in preventing and improving oral diseases. In particular, since nonionic fungicides such as triclosan and isopropylmethylphenol have a characteristic that the antibacterial spectrum tends to be wide, for example, triclosan is known to be blended in a dentifrice composition as a plaque inhibitor ( Patent Document 1), and phenolic compounds such as thymol are also known to suppress plaque by blending in oral compositions (Patent Document 2).

  However, these bactericides are effective against pathogenic bacteria (floating bacteria) in a state where they are suspended in saliva alone, but when they are incorporated into preparations such as oral products, the ingredients in the preparations, for example, The effect is inactivated by the inactivation of the active site of the fungicide by various surfactants added for the precipitation and solubilization of the fungicide due to moisture contained in the preparation, and the penetration ability to plaque is weak The current situation is that there are many, and it does not act effectively and sufficiently on the pathogenic bacteria present in the plaque. In addition, isopropylmethylphenol is known as an effective drug against pathogenic bacteria in dental plaque (Non-Patent Document 1), but the bactericidal effect of isopropylmethylphenol against floating bacteria is weak compared to triclosan and the like. There is a problem.

  On the other hand, it has been proposed that a glycerin derivative is effective as an antibacterial agent and can be preferably used for a composition for external use in skin, a cleaning material, food, and the like (Patent Documents 3 and 4). Patent Document 5 discloses a 1,2-alkanediol, and further, an antiseptic fungicide in combination with benzoic acid and its salt, and Patent Document 6 discloses 1,2-alkanediol and an antiperspirant, Deodorant cosmetics containing body odor prevention agents such as bactericides and deodorants have been proposed. However, there is a problem that the amount of alkanediol is limited because it is hardly soluble in water.

  From such a current situation, development of a new technology that is excellent in sterilization or bacteriostatic effect of pathogenic bacteria and that can effectively suppress or prevent plaque formation on the tooth surface is desired.

JP 60-239410 A Special table 2001-526202 gazette JP 2005-132777 A JP 2005-132778 A Japanese Patent Laid-Open No. 11-322591 JP 2003-81801 A

DENTAL DIAMOND: 30,75-79,2005.

Plaque present invention has been made in view of the above circumstances, exhibit high bactericidal activity against pathogenic bacteria in the oral cavity, it can be effectively suppressed or prevent plaque formation, and, with excellent usability An object is to provide a formation inhibitor .

The present inventors have made intensive studies for achieving the above object, in combination in a specific ratio and (A) benzyl glyceryl ether, and (B) nonionic bactericidal component isopropyl methylphenol, and (C ) It has been found that by blending alcohol and / or nonionic surfactant, it exhibits high bactericidal power against pathogenic bacteria in the oral cavity and can effectively suppress or prevent plaque formation on the tooth surface. .

That is, in the present invention, as is clear from the experimental examples described later, by combining benzyl glyceryl ether and a specific nonionic bactericidal component in a specific ratio, and using alcohol and / or a nonionic surfactant together, High bactericidal effect to kill periodontal disease-causing bacteria such as obligate anaerobic gram-negative bacilli such as Porphyromonas gingivalis that floats in the oral cavity, and plaque is formed on the tooth surface. Therefore, it is effective as a preparation for suppressing or preventing plaque formation . Such operational effects of the present invention are exceptional that cannot be achieved when these components are used alone or when both components are used in an inappropriate proportion.

It is known that glycerin derivatives such as benzyl glyceryl ether are used as an antibacterial or bactericidal agent in hair dye compositions, skin external preparations and the like (Patent Documents 3 and 4). It does not inhibit the pathogenic bacteria that cause the disease and prevent plaque formation. These techniques, by blending the oral composition in combination with benzyl glyceryl ether and a particular nonionic bactericidal component, exhibit much higher bactericidal activity against oral bacteria such as periodontal disease-causing bacteria Moreover, it is difficult to imagine that an excellent bactericidal effect that can suppress or prevent the formation of plaque on the tooth surface is obtained. In addition, when the present inventors evaluated the bactericidal power with respect to oral bacteria about the technique as described in these patent documents, the effect was very weak.

Therefore, the present invention provides the following plaque formation inhibitor.
Claim 1:
(A) benzyl glyceryl ether 0.5-10 mass%,
(B) Isopropyl methylphenol 0.02 to 0.5% by mass,
(C) 0.1 to 40% by mass of an alcohol (C-1) selected from monovalent lower alcohols having 1 to 4 carbon atoms and divalent and trivalent polyhydric alcohols and / or carbons of alkyl groups Nonionic interface selected from polyoxyethylene alkyl ethers having a number of 12 to 18 and an average addition mole number of ethylene oxide of 2 to 30 moles and a polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 20 to 100 moles 0.05-4 mass% of activator (C-2)
A plaque formation inhibitor containing and having a mass ratio of (A) / (B) of 10 to 200.
Claim 2 :
In the alcohol (C-1), the case of using a lower alcohol is not less than 15 wt% the amount of that, the case of using the polyhydric alcohol according to claim 1, wherein the amount of that is less than 35 wt% Plaque formation inhibitor.

The plaque formation inhibitor of the present invention has a high bactericidal power to sterilize pathogenic bacteria floating in the oral cavity, has an excellent effect of suppressing or preventing plaque formation, and has a good feeling of use. It is useful as a preparation for preventing or improving oral disease by suppressing formation.

Hereinafter, the present invention will be described in more detail. The plaque formation inhibitor of the present invention contains (A) benzylglyceryl ether, (B) isopropylmethylphenol , (C) alcohol and / or a nonionic surfactant .

In the present invention, examples of (A) benzylglyceryl ether include 3- (benzyloxy) 1,3-propanediol, 3- (benzyloxy) 1,2-propanediol, and the like. You may use together.

Benzyl glyceryl ether can be produced by a general synthesis method, and those obtained by a known synthesis method can be used. Specifically, it can be produced using halohydrin such as glycidol, glycerin, chlorohydrin, bromohydrin, and benzyl alcohol or phenol. In particular, benzyl alcohol and glycerin are reacted in the presence of zeolite as a catalyst (etherification reaction). Thus, it is preferable to produce benzylglyceryl ether with high yield and high selectivity while suppressing the formation of by-products. Here, the high selection ratio, indicating a selectivity of 90%.
The reaction conditions for the etherification reaction of benzyl alcohol and glycerin in the presence of zeolite are not particularly limited and can be appropriately selected depending on the purpose. For example, when the reaction conditions of the synthesis method proposed by the applicant in Japanese Patent Application No. 2008-233894 are employed, benzyl glyceryl ether can be obtained with higher yield and higher selectivity. Specifically, the reaction temperature is usually from room temperature to 300 ° C, and preferably from 100 to 200 ° C. If the reaction temperature is higher than 300 ° C., side reaction proceeds and there is concern about a decrease in the selectivity of the monoether, and if it is lower than room temperature, the reaction rate may be low and not efficient. Moreover, reaction time is normally performed for 30 minutes-20 hours, and it is preferable to carry out for 3 to 10 hours especially. If the reaction time is shorter than 30 minutes, the reaction may not proceed and a large amount of raw material may be recovered. If the reaction time is longer than 20 hours, the side reaction proceeds and there is a concern that the monoether selectivity may be lowered.

  As benzyl glyceryl ether, benzyl glyceryl ether obtained by the above method can be used. Moreover, as benzyl glyceryl ether, you may use a commercial item, for example, 3- (benzyloxy) 1,3-propanediol (made by Tokyo Chemical Industry Co., Ltd.), 3- (benzyloxy) 1,2-propane. Diol (made by ALDRICH) etc. can be mentioned.

The blending amount of benzyl glyceryl ether is preferably 0.1 to 20% (mass%, the same applies hereinafter), particularly 0.5 to 10%, particularly 1.0 to 10%, based on the total amount of the composition. The amount can not be obtained a sufficient floating bacteria germicidal and plaque formation inhibiting effect is less than 0.1%, more than 20%, the or plaque formation inhibiting effect, inferior Ru usability.

Component (B) is isopropylmethylphenol (3-methyl-4-isopropylphenol) , which is a nonionic bactericidal component .

  The blending amount of the component (B) is preferably 0.01 to 1%, particularly 0.02 to 0.5% of the whole composition. The inhibitory effect may not be obtained, and if it exceeds 1%, the use feeling of the composition may be inferior.

In the present invention, the mixing ratio of the component (A) and the component (B) (the mass ratio of (A) / (B)) is 5 to 200. It is important in terms of feeling. When (A) / (B) is less than 2, satisfactory fungicidal sterilizing power and plaque formation inhibitory effect cannot be obtained, and when 500 is exceeded, no floating fungicidal power and plaque formation inhibitory effect are obtained. It is inferior to the feeling of use of things.

  (C) It is considered that the alcohol and / or nonionic surfactant can act as a solubilizer when the component (B) is blended to effectively develop the blending effect of the component (B). In addition, the alcohol and the nonionic surfactant may be used alone or in combination of two or more. The alcohol or the nonionic surfactant may be used alone or in combination with the alcohol and the nonionic surfactant.

  Examples of the alcohol include lower alcohols and polyhydric alcohols, and monovalent lower alcohols having 1 to 4 carbon atoms such as ethanol, isopropanol, butanol, and propanol, glycerin, ethylene glycol, diethylene glycol, hexylene glycol, propylene glycol, and polyethylene. Examples include divalent or trivalent polyhydric alcohols such as glycol 200 to 20,000 and polypropylene glycol 300 to 4,000. Among these, ethanol, propylene glycol, and polyethylene glycol 400 are particularly preferable.

The blending amount of the alcohol may be 0%, and is preferably 0 to 35%, particularly 0.1 to 35%, especially 0.1 to 30% of the whole composition. If the blending amount exceeds 35%, the usability may be inferior.
The upper limit of the amount of the lower alcohol is preferably 15% or less, particularly 10% or less of the entire composition. If it exceeds 15%, irritation may occur and the feeling of use may be inferior. Moreover, the upper limit of the blending amount of the polyhydric alcohol can be 35% or less, particularly 30% or less of the entire composition, and even if it exceeds 35%, the effectiveness such as the ability to sterilize the floating bacteria is not obtained. On the other hand, the feeling of use may be reduced.

There is no restriction | limiting in particular as nonionic surfactant, Usually, what is mix | blended with the composition for oral cavity can be used.
Nonionic surfactants include polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene alkyl ethers such as polyoxyethylene stearyl ether, polyoxyethylene fatty acid esters such as polyoxyethylene hydrogenated castor oil, polyoxyethylene Polyoxyethylene sorbitan fatty acid ester such as sorbitan monolaurate, polyoxyethylene sorbitan monostearate, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene polyoxypropylene fatty acid ester, sucrose fatty acid ester, maltose fatty acid ester, lactose Sugar fatty acid esters such as fatty acid esters, sugar alcohol fatty acid esters such as maltitol fatty acid esters and lactitol fatty acid esters, sols Such as fatty acid ester, and the like.
Among these nonionic surfactants, polyoxyethylene alkyl ethers and polyoxyethylene fatty acid esters, particularly polyoxyethylenes having an alkyl group having 12 to 18 carbon atoms and an average addition mole number of ethylene oxide of 2 to 30 moles. Polyoxyethylene hydrogenated castor oil having an average addition mole number of alkyl ether and ethylene oxide of 20 to 100 mol is preferred.

  Specifically, polyoxyethylene (2) lauryl ether, polyoxyethylene (20) lauryl ether, polyoxyethylene (25) lauryl ether, polyoxyethylene (2) cetyl ether, polyoxyethylene (10) cetyl ether, Polyoxyethylene (15) cetyl ether, polyoxyethylene (20) cetyl ether, polyoxyethylene (5) stearyl ether, polyoxyethylene (15) stearyl ether, polyoxyethylene (20) stearyl ether, polyoxyethylene (15 ) Oleyl ether, polyoxyethylene (20) hydrogenated castor oil, polyoxyethylene (40) hydrogenated castor oil, polyoxyethylene (60) hydrogenated castor oil, polyoxyethylene (80) hydrogenated castor oil, polyoxyethylene 100) hardened castor oil, sucrose fatty acid esters, polyglycerol fatty acid ester (decaglyceryl laurate), and the like. Among these, polyoxyethylene (20) hydrogenated castor oil, polyoxyethylene (60) hydrogenated castor oil, and polyoxyethylene (5) stearyl ether are more preferable. In addition, the numerical value in the said parenthesis is the average addition mole number of ethylene oxide.

  The nonionic surfactant may be added in an amount of 0%, and is preferably 0 to 4%, particularly 0.05 to 4%, particularly 0.1 to 3.5% of the entire composition. If the blending amount exceeds 4%, even if the component (B) is dissolved, the bactericidal action is deactivated by the nonionic surfactant, and there may be cases where sufficient antibacterial sterilizing power and plaque formation inhibiting effect cannot be obtained. .

  (C) The total amount of alcohol and / or nonionic surfactant is suitably 0.05 to 35%, particularly 0.1 to 30% of the total composition. If the blending amount is less than 0.05%, the component (B) may not be sufficiently dissolved, and the effects of the present invention may not be obtained satisfactorily.

The composition for oral cavity containing the plaque formation inhibitor of the present invention can be in the form of a solid, solid, liquid, liquid, gel, paste, gum or the like, and is a toothpaste, liquid dentifrice, liquid dentifrice. It is possible to make various dosage forms such as dentifrice such as toothpaste, mouthwash, mouthwash, troche, chewing gum, etc., and the manufacturing method may adopt the usual method according to the dosage form it can. In this case, other appropriate components can be blended in addition to the components described above depending on the purpose of the composition, dosage form, and the like. For example, in the case of a toothpaste, abrasives, thickeners, binders, surfactants, sweeteners, preservatives, active ingredients, pigments, fragrances, etc. can be blended, and these ingredients are mixed with water. it can.

As abrasives, silica-based abrasives such as silica gel, precipitated silica, aluminosilicate, zirconosilicate, dicalcium phosphate dihydrate and anhydrous, calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, Examples thereof include tertiary magnesium phosphate, zeolite, zirconium silicate, hydroxyapatite, tertiary calcium phosphate, fourth calcium phosphate, and synthetic resin-based abrasive.
The amount of these abrasives is adjusted depending on the dosage form, and for example, it can be 10 to 50% for toothpaste and 0 to 30% for liquid toothpaste.

  In the case of paste-like compositions such as toothpaste, an organic or inorganic binder can be added as a binder, for example, carrageenan, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, cellulose derivatives such as sodium carboxymethylhydroxyethylcellulose, alginic acid, etc. Alginate derivatives such as sodium and propylene glycol alginate, gums such as xanthan gum, tragacanth gum, gela gum, karaya gum and gum arabic, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, synthetic organic binders such as polyvinylpyrrolidone, silica gel, Inorganic binders such as aluminum silica gel, bee gum, and laponite can be blended (the blending amount is usually 0.3 to 10%).

  As the surfactant, an amphoteric surfactant may be added. For example, N-alkyldiaminoethylglycine such as N-myristyldiaminoethylglycine, N-alkyl-N-carboxymethylammonium betaine, 2-alkyl-1- Hydroxyethyl imidazoline betaine sodium or the like may be blended in an amount of 0.2 to 2% of the total composition.

In the present invention, as the surfactant, a component other than the nonionic surfactant (C), specifically higher alkyl sulfate ester salt, N-acyl sarcosinate described later, and other anionic properties Surfactants such as sodium dodecylbenzenesulfonate, hydrogenated coconut fatty acid monoglyceride sodium monosulfate, sodium lauryl sulfoacetate, sodium N-palmitoyl glutamate, N-acyl glutamate, N-methyl-N-acyl taurate sodium, N- You may mix | blend methyl-N-acylalanine sodium, alpha-olefin sodium sulfonate, etc. As the higher alkyl sulfate ester salt, those having an alkyl group having 8 to 18 carbon atoms, particularly 12 to 14 carbon atoms are suitable, and alkali metal salts such as sodium salts and potassium salts are used. Specific examples include sodium lauryl sulfate, potassium lauryl sulfate, and sodium myristyl sulfate, and sodium lauryl sulfate is particularly preferable from the viewpoints of solubility and feeling of use. As the N-acyl sarcosine salt, those having an acyl group having 10 to 18 carbon atoms, particularly 12 to 14 carbon atoms are preferred, and alkali metal salts such as sodium salts are used. Specific examples include sodium N-acyl sarcosine such as sodium N-lauroyl sarcosine and sodium N-myristoyl sarcosine. In the present invention, the blending amount of the surfactant as an optional component is such that the total content of the surfactant including the nonionic surfactant of the component (C) is 0 to 6%, particularly 0. The range may be 0.05 to 5.5%.

  As the thickener, sugar alcohols such as sorbitol, xylitol, erythritol, maltitol, and lactitol can be blended (the blending amount is usually 5 to 70%).

  Examples of the sweetening agent include saccharin sodium, stevioside, dipotassium glycyrrhizinate, pelartin, thaumatin, neohesperidyl dihydrochalcone, aspartylphenylalanine methyl ester and the like. Examples of the preservative include paraoxybenzoic acid esters such as methylparaben and butylparaben, benzoic acid such as sodium benzoate, and salts thereof.

  Perfumes are anise oil, eucalyptus oil, winter green oil, cassia oil, clove oil, sage oil, lemon oil, orange oil, cardamom oil, coriander oil, mandarin oil, lime oil, lavender oil, rosemary oil, laurel oil, Natural perfumes such as camomile oil, caraway oil, bay oil, lemongrass oil, pine needle oil, neroli oil, rose oil, jasmine oil, perilla oil, patchouli oil, iris concrete, absolute rose, orange flower, and these natural Fragrance processed (percentage cut, rear end cut, fractional distillation, liquid-liquid extraction, essence, powdered fragrance, etc.), and carvone, anethole, cineol, methyl salicylate, ethyl salicylate, cinnamic aldehyde Eugenol, 3-l-menthoxypropane-1,2-dio , Linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted-paramentane-3-carboxamide, monomenthyl succinate, pinene, octylaldehyde, citral, pregon, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate Rate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, hexanal, isoamyl alcohol, hexenol, dimethyl sulfide, cycloten, furfural, trimethyl pyrazine, ethyl lactate, ethyl thioacetate, etc. Single flavor, strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape Known flavor materials used in oral compositions, such as blended flavors such as flavors, mango flavors, butter flavors, milk flavors, fruit mix flavors, tropical fruit flavors, tea flavors, etc. It is not limited.

  Moreover, although a compounding quantity is not specifically limited, It is preferable to use said fragrance | flavor raw material 0.000001 to 1% in a composition. Moreover, as a fragrance | flavor for fragrance | flavor which uses the said fragrance | flavor raw material, it is preferable to use 0.001-2.0% during a composition.

  In the composition for oral cavity of the present invention, as an active ingredient, enzymes such as dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, SOD (superoxide dismutase), sodium monofluorophosphate, potassium monofluorophosphate, etc. Alkali metal monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, phenolic compounds such as triclosan, eugenol, borneol, cinnamaldehyde, farnesol, tranexamic acid, epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, Dihydrocholestanol, glycyrrhizic acid, glycyrrhetinic acid, bisabolol, glycerophosphate, chlorophyll, chlorhexidine gluconate, alkyldiamide methyl methacrylate The effect of the present invention can be achieved by using one or more known active ingredients such as glycine, sodium chloride, zinc chloride, water-soluble inorganic phosphate, vitamin A, vitamin B group, vitamin C, vitamin E and their derivatives and their derivatives. An effective amount can be blended within a range not hindering.

  The material in particular of the container which accommodates the composition for oral cavity of this invention is not restrict | limited, Usually, the container used for the composition for oral cavity can be used. Specifically, plastic containers such as polyethylene, polypropylene, polyethylene terephthalate, and nylon can be used.

  EXAMPLES Hereinafter, although a synthesis example, an experiment example, an Example, and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, the blending amounts are all mass%.

[Synthesis example]
Production method of benzylglyceryl ether In a 50 mL eggplant-shaped flask, 10.2 g of glycerin (0.11 mmol: manufactured by Wako Pure Chemical Industries, Ltd.), 12.4 g of benzyl alcohol (0.11 mmol: manufactured by Wako Pure Chemical Industries, Ltd.), zeolite catalyst (5524G, manufactured by ZEOLYST) 0.5 g was added and reacted at 150 ° C. for 7 hours (etherification reaction). The reaction solution was acetylated using 0.5 g of pyridine and acetic anhydride, and GC analysis was performed under the following conditions to confirm that the desired benzyl glyceryl ether was obtained with a yield of 70% and a selectivity of 97%. did. The reaction solution was gradually depressurized from 760 mmHg at 150 ° C., benzyl alcohol was distilled off at 5 mmHg, then the temperature was raised to distill off the liquid containing glycerin at 170 ° C., and the temperature was gradually raised to 180 ° C. Benzyl glyceryl ether was distilled off to obtain the desired product.

GC (gas chromatography) analysis condition measuring device; HP-5890 made by Hewlett-Packard
Column; HP Ultra2
Oven temperature: 100 ° C. → 300 ° C. (10 ° C./min.), Held for 10 minutes Carrier gas: He
Inlet temperature: 320 ° C Detector temperature: 320 ° C (FID)
Split ratio; 50: 1 injection volume; 1 μL
-Yield and selectivity The yield and selectivity of benzyl glyceryl ether were calculated | required by the following formula | equation (1), (2) on the basis of the area ratio of the said GC analysis.
Yield (%) = [TM / (G + TM + BP)] × 100 Formula (1)
Selectivity (%) = (TM / R) × 100 Formula (2)
In the formulas (1) and (2), TM represents the GC area ratio in the reaction solution of benzyl glyceryl ether as the target product, G of glycerin as the raw material, and BP of the reaction byproduct. In addition, the reaction by-product shown by BP shows all the reaction products derived from this glycerol obtained by this reaction except TM, for example, 1, 3- di (benzyloxy) which has two benzyl groups in glycerol. ) 2-propanol, diglycerin and the like.
R represents the total GC area ratio of all reaction products in the reaction solution. Here, the “total reaction product” refers to all products other than glycerin and benzyl alcohol contained in the reaction solution after completion of the reaction. In addition, the thing of the GC area ratio of less than 1% was rounded down and calculated.

[Experimental example]
Test compositions having the compositions shown in Tables 1 to 3 were prepared as follows and evaluated. The results are shown in Tables 1-3 .
Preparation of test composition :
Test compositions prepared in a 100 mL beaker with the composition shown in Tables 1 to 3 using purified water by a conventional method, and after confirming that the pH is near neutral, the total amount is adjusted to 100 g. Got. The reagents used are as follows. As benzyl glyceryl ether, the one obtained in the above synthesis example was used.

Details of the reagents used are as follows. POE is an abbreviation for polyoxyethylene.
Isopropylmethylphenol: Wako Pure Chemical Industries, Ltd. Thymol: Wako Pure Chemical Industries, Ltd. Menthol: l-menthol, Wako Pure Chemical Industries, Ltd. Hinokitiol: Wako Pure Chemical Industries, Ltd. POE (20) hydrogenated castor oil: Nippon Surfactant, Inc. POE (60) hydrogenated castor oil: manufactured by Nippon Surfactant Co., Ltd. Monostearic acid POE sorbitan: manufactured by Nikko Chemicals Co., Ltd. POE sorbitan monolauric acid ester: manufactured by Nikko Chemicals Co., Ltd. POE (15) lauryl ether: manufactured by Nikko Chemicals Co., Ltd. propylene glycol: Wako Pure Chemical Industries, Ltd. Benzethonium chloride: Wako Pure Chemical Industries, Ltd. Benzalkonium chloride: Wako Pure Chemical Industries, Ltd. Sodium lauryl sulfate: Wako Pure Chemical Industries, Ltd. Lauroyl sarcosine sodium: Kawaken Fine Chemicals Corporation 1,2-octanediol: Tokyo Kasei Craft Company made chloride Dekariumu: Sigma

Evaluation of the ability to sterilize airborne bacteria :
40 μL of Porphyromonas gingivalis ATCC33277 purchased from American Culture Collection (ATCC) is added to 4 mL of Todd Hewitt broth culture solution (THBHM ^{* 1} ) containing 5 mg / L hemin and 1 mg / L vitamin K, respectively. Then, anaerobic culture (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) was performed overnight at 37 ° C.

The bacterial solution of Porphyromonas gingivalis was added to 4 mL of the test composition solution so as to have a final concentration of 1.0 × 10 ⁸ cells / mL, and reacted at 37 ° C. for 3 minutes. Immediately thereafter, this bacterial solution was serially diluted (6 levels of 10-fold dilution), and each bacterial solution was smeared on a blood agar plate medium ^{* 2} . The plate medium is anaerobically cultured (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) until colonies can be confirmed with the naked eye. After counting the number of colonies on each plate medium, the number of viable bacteria (unit: log cfu / HA) Plate, abbreviation of CFU: colony forming unit). The floating bacteria bactericidal power of the test composition with Comparative Example 1 as a control (Tables 1 and 2 is Comparative Example I-1, Table 3 is Comparative Example II-1, hereinafter the same) is calculated from the following formula. Based on the values, the following evaluation criteria were used.
Airborne germicidal power of the test composition for Comparative Example 1 =
-Log (Number of Porphyromonas gingivalis after treatment with test composition / Number of Porphyromonas gingivalis after treatment with the composition of Comparative Example 1)

Evaluation criteria:
◎: Airborne bacteria sterilization power 3.5 or more and 7 or less ○: Airborne bacteria sterilization power 2.0 or more and less than 3.5 △: Airborne bacteria sterilization power 0.5 or more and less than 2.0 ×: Airborne bacteria sterilization power less than 0.5

^{* 1} Composition of THBHM: Expressed by mass in 1 liter.
Todd Hewitt Broth (Becton and Dickinson): 30g / L
Hemin (Sigma Aldrich): 5mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries): 1mg / L
Distilled water: Residue (Measured up to a total volume of 1 L and autoclaved at 121 ° C. for 15 minutes.)
^{* 2} Composition of blood agar plate medium: Expressed by mass in 1 liter.
Todd Hewitt Broth (Becton and Dickinson):
30g / L
Agar (Becton and Dickinson): 15g / L
Hemin (manufactured by Sigma): 5mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries): 1mg / L
Distilled water: Residue (Upper volume to 1L, autoclaved at 121 ° C for 15 minutes,
After cooling to 50 ° C., the following equine defibrinated blood was aseptically added and dispensed into a petri dish (manufactured by Sansei Medical Equipment Co., Ltd.). )
Horse defibrinated blood (manufactured by Japan Biotest Laboratories)
(After autoclaving, cool to 50 ° C and add.)

Evaluation of feeling of use (taste / odor) of the test composition The feeling of use (taste / odor) of the test composition was evaluated by a human use test. That is, 10 test subjects stir a stoppered test tube containing 5 g of the test composition with a vortex mixer for 10 seconds, and then the odor of the test composition was evaluated according to the following score using Comparative Example 1 as a control. The results were obtained from the average of 10 people according to the following evaluation criteria.

Score:
4 points: Taste and smell are better than those of Comparative Example 1.
3 points: The taste and smell are equivalent to those of Comparative Example 1.
2 points: A slightly different taste and smell compared to Comparative Example 1 are felt.
1 point: Taste and smell clearly different from Comparative Example 1 are felt.
Evaluation criteria:
◎: The score is 3.5 or more and 4 or less ○: The score is 3 or more and less than 3.5 △: The score is more than 2 and less than 3 ×: The score is 2 or less

Evaluation of solubility The solubility of the test composition was evaluated by the following method. That is, using a 100 mL beaker according to the test composition preparation method, the total amount was adjusted to 100 g, stirred for 1 minute at 360 rpm, and allowed to stand for 3 minutes. Was evaluated.
Grade ○: Transparent △; Slight turbidity or precipitation is observed ×: Clearly turbidity or precipitation is observed

Beagle canine plaque inhibition test An experiment was conducted using a total of 6 teeth of left and right lower jaws P2 to P4 of male beagle dogs (4 heads) as control teeth. By scaling and polishing the gingival margin from above the gingival margin of the target tooth to completely remove the adhered plaque and calculus, the composition of Comparative Example 1 was used as a control on one jaw and the surface on the other jaw. 2 mL of the test composition shown in 1-3 was administered by spraying twice a day. On the fifth day from the start of the experiment, the oral cavity was thoroughly washed, and the total amount of plaque formed was scraped, and the amount of plaque was determined by measuring the amount of protein by the Lowry method ^{* 3} . The results were evaluated according to the following evaluation criteria from the calculated values after calculating the plaque formation inhibitory effect of the test composition with Comparative Example 1 as a control from the following formula.
Plaque formation inhibitory effect (%) of test composition with Comparative Example 1 as control =
((Plate formation amount after treatment with the composition of Comparative Example 1−Plate formation amount after treatment with the test composition) / (Plate formation amount after treatment with the composition of Comparative Example 1)) × 100

Evaluation criteria:
◎: 40% or more ○: 30% or more and less than 40% △: 20% or more and less than 30% ×: less than 20%
^{* 3} reagent Micro BCA ^TM protein assay kit (Micro BCA ^TM Protein Assay Kit, manufactured by PIERCE Co.)

  As is clear from the results of Tables 1 and 2, when (A) benzylglyceryl ether, (B) a specific nonionic fungicide, (C) any of alcohol and / or nonionic surfactant, Even if the components (A) to (C) are used in combination, if the blending ratio of (A) / (B) is inappropriate, the high antibacterial sterilizing power and the plaque formation inhibitory effect are not exhibited and the feeling of use While it may be inferior, (A) to (C) are combined, and (A) / (B) is a specific ratio, so that the bactericidal fungicidal power and plaque formation inhibitory effect are high, and It turns out that it also has an excellent usability. Even when 1,2-octanediol was used in place of benzyl glyceryl ether, or when phenoxyethanol was used in combination with benzyl glyceryl ether, the above effect was not achieved.

  Examples are shown below. In addition, the composition of the fragrance | flavor used in the following example is as follows. Note that fragrances A to D do not include menthol.

* Fruit mix flavor FM3000 (mixed fragrance)
Strawberry flavor 40%
Apple flavor 15
Melon Flavor 17
Banana Flavor 10
Peach flavor 5
Orange oil 2.5
Raspberry flavor 2.0
Pineapple flavor 1.5
Grape flavor 1.0
Tropical fruit flavor 1.5
Milk flavor 1.0
Tea flavor 0.5
Grapefruit oil 0.5
Lemon oil 0.5
Rose oil 0.2
Solvent residue
Total 100.0%

  When an oral composition having the following composition was prepared by a conventional method and evaluated in the same manner, it was confirmed that the composition was excellent in any effect.

[Example 1] Toothpaste dicalcium phosphate 45.0%
Silica anhydride 2.0
Sorbit 25.0
Propylene glycol (Dow Chemical Co., Ltd.) 2.0
Sodium carboxymethylcellulose 1.0
Sodium alginate 0.5
Sodium lauryl sulfate (manufactured by Toho Chemical Industry Co., Ltd.) 1.2
Polyoxyethylene (60) hydrogenated castor oil (manufactured by Nippon Surfactant) 0.8
Saccharin sodium 1.0
Sodium benzoate 0.1
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Benzyl glyceryl ether (manufactured product in synthesis example) 2.0
Fragrance A 1.0
Purified water remaining
Total 100.0%
((A) benzyl glyceryl ether / (B) isopropylmethylphenol = 40 )

[Example 2 ] Toothpaste zirconosilicate 25.0%
Silica anhydride 2.0
Sorbit liquid 40.0
Polyethylene glycol 400 5.0
Sodium polyacrylate 1.0
Sodium lauryl sulfate (manufactured by Toho Chemical Industry Co., Ltd.) 0.8
Lauroyl sarcosine sodium (manufactured by Kawaken Fine Chemical Co., Ltd.) 0.2
Saccharin sodium 0.2
Methyl paraoxybenzoate 0.1
Butyl paraoxybenzoate 0.1
Benzyl glyceryl ether (manufactured product in synthesis example) 5.0
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.1
Fragrance C 1.0
Purified water remaining
Total 100.0%
((A) benzyl glyceryl ether / (B) isopropylmethylphenol = 50 )

[Example 3 ] Liquid dentifrice glycerin (manufactured by Sakamoto Pharmaceutical Co., Ltd.) 35.0%
Sorbit liquid 15.0
Propylene glycol (Dow Chemical Co.) 5.0
Silicic anhydride 0.3
Sodium lauryl sulfate (manufactured by Toho Chemical Industry Co., Ltd.) 1.0
Polyoxyethylene (60) hydrogenated castor oil (manufactured by Nippon Surfactant) 0.7
Saccharin sodium 0.2
Sodium benzoate 0.3
Benzyl glyceryl ether (manufactured product in synthesis example) 2.0
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Fragrance D 1.0
Tranexamic acid 0.1
Purified water remaining
Total 100.0%
((A) benzyl glyceryl ether / (B) isopropylmethylphenol = 40 )

[Example 4 ] Mouthwash ethanol (manufactured by New Energy and Industrial Technology Development Organization) 10.0%
Propylene glycol (Dow Chemical Co., Ltd.) 2.0
Glycerin (made by Lion) 2.0
Polyoxyethylene (60) hydrogenated castor oil (manufactured by Nippon Surfactant) 0.3
Xylitol 4.0
Sodium lauryl sulfate (manufactured by Toho Chemical Industry Co., Ltd.) 0.05
Lauroyl sarcosine sodium (manufactured by Kawaken Fine Chemical Co., Ltd.) 0.05
Dye 0.001
Fragrance B 0.3
Lysozyme chloride 0.3
Potassium nitrate 5.0
Ammonium sulfate 0.2
Benzyl glyceryl ether (manufactured product in synthesis example) 0.5
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Purified water remaining
Total 100.0%
((A) benzyl glyceryl ether / (B) isopropylmethylphenol = 10 )

[Example 5 ] Mouthwash ethanol (manufactured by New Energy and Industrial Technology Development Organization) 10.0%
Glycerin (made by Lion) 2.0
Polyoxyethylene (60) hydrogenated castor oil (manufactured by Nippon Surfactant) 0.2
Saccharin sodium 0.1
Sodium lauryl sulfate (manufactured by Toho Chemical Industry Co., Ltd.) 0.1
Fragrance A 3.0
Benzyl glyceryl ether (manufactured product in synthesis example) 2.0
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Hinokitiol (Wako Pure Chemical Industries, Ltd.) 0.1
Purified water remaining
Total 100.0%
((A) benzyl glyceryl ether / (B) of isopropyl methyl phenol = 40)

[Example 6 ] Trochixylitol 25.0%
Arabic gum 5.0
Polyoxyethylene (20) hydrogenated castor oil (manufactured by Nippon Surfactant) 0.1
Talc 2.0
Magnesium stearate 0.7
Fragrance A 3.0
Benzyl glyceryl ether (manufactured product in synthesis example) 5.0
Isopropylmethylphenol (Wako Pure Chemical Industries, Ltd.) 0.05
Peppermint oil 2.0
Purified water remaining
Total 100.0%
((A) benzyl glyceryl ether / (B) isopropylmethylphenol = 100)

Claims (2)

(A) benzyl glyceryl ether 0.5-10 mass%,
(B) Isopropyl methylphenol 0.02 to 0.5% by mass,
(C) 0.1 to 40% by mass of an alcohol (C-1) selected from monovalent lower alcohols having 1 to 4 carbon atoms and divalent and trivalent polyhydric alcohols and / or carbons of alkyl groups Nonionic interface selected from polyoxyethylene alkyl ethers having a number of 12 to 18 and an average addition mole number of ethylene oxide of 2 to 30 moles and a polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 20 to 100 moles 0.05-4 mass% of activator (C-2)
A plaque formation inhibitor containing and having a mass ratio of (A) / (B) of 10 to 200. In the alcohol (C-1), the case of using a lower alcohol is not less than 15 wt% the amount of that, the case of using the polyhydric alcohol according to claim 1, wherein the amount of that is less than 35 wt% Plaque formation inhibitor.