JPWO2009020010A1 - Liquid oral composition and method for improving bactericidal activity of cationic bactericides - Google Patents

Abstract

In the liquid oral composition, (A) cetylpyridinium chloride 0.01 to 0.1% by mass (B) sodium lauroyl sarcosine 0.02 to 0.3% by mass (C) The average added mole number of ethylene oxide is 40 to 40%. 100 mol of polyoxyethylene hydrogenated castor oil is blended, the mass ratio of (A) / (B) is 0.3 to 3, and the mass ratio of (C) / ((A) + (B)) is 1.0. ~ 20. According to the present invention, the bactericidal agent quickly penetrates into the cariogenic biofilm, exhibits excellent bactericidal power against cariogenic bacteria, and causes the occurrence of orientation and staining even at low temperature storage. A liquid oral composition that is suppressed, has good appearance stability, and is effective in preventing dental caries can be obtained.

Description

  The present invention effectively disinfects the cariogenic biofilm in the oral cavity and exhibits excellent bactericidal power against cariogenic bacteria, as well as the occurrence of orientation and scratches during low-temperature storage. The present invention relates to a liquid oral composition that is suppressed and has good appearance stability, and a method for improving the bactericidal activity of a cationic bactericide.

  Caries occur when oral biofilms formed by caries-causing bacteria such as Streptococcus mutans bacteria adhere to the tooth surface in the oral cavity, and the teeth are decalcified by the acid produced in the biofilm.

  Thus, as a means for preventing caries, in the field of liquid oral compositions, means for sterilizing caries-causing bacteria by incorporating various bactericides are used. In particular, cationic bactericides such as benzethonium chloride and cetylpyridinium chloride have high bactericidal activity against cariogenic bacteria and have a property of being easily adsorbed to the surface of oral tissues such as teeth and oral mucosa. It is blended in many oral compositions.

  However, these cationic fungicides exert a good bactericidal effect against airborne microbes, but have a low penetrating ability into the oral biofilm, especially against cariogenic bacteria in the oral biofilm. On the other hand, there was a problem that a sufficient bactericidal effect was not exhibited.

  Examples of oral sterilization techniques using a cationic fungicide include, for example, an adsorption promotion technique (see Patent Document 1) by blending polyphosphoric acid and polyglycerin fatty acid ester with a cationic fungicide, and erythritol as a cationic fungicide. , Xylitol, palatinit, maltitol, lactitol, anti-plaque formation technology by inhibiting protein adsorption to the tooth surface (see Patent Document 2), sterilization by adding polyvinyl alcohol to cationic fungicide Tooth Adsorbability Enhancement Technology (Refer to Patent Document 3), Cationic Bactericide Formulation Oral Composition By Mixing Water-soluble Fragrance with No Anionic Surfactant and Nonionic Surfactant Improved bactericidal activity (see Patent Document 4), cationic bactericides and polyvinylpyrrolide Hints, that a composition containing no surfactant other than the cationic bactericide, a technique for improving the antimicrobial activity and stability with time due to the oral composition (see Patent Document 5) are disclosed. However, even in these techniques, although a high bactericidal power against airborne bacteria in the oral cavity is exhibited, the bactericidal power against cariogenic bacteria in the biofilm is insufficient and is not satisfactory.

In addition, a technique for enhancing the biofilm penetration sterilizing power of a nonionic fungicide such as isopropylmethylphenol by blending an anionic surfactant such as sodium lauryl sulfate with the liquid oral composition (Patent Documents 6 and 7) Have been proposed). Furthermore, the bactericidal effect of dehydroabietic acid in the oral cavity is enhanced by the combined use of an anionic surfactant such as sodium lauryl sulfate (see Patent Document 8). It is possible to sterilize pathogenic bacteria in plaque by blending cationic fungicide and suppress plaque formation (see Patent Document 9), hydroxypyridone derivative which is a cationic polymer, hydroxyethylcellulose / dimethyldiallylammonium It has been proposed that the retention can be improved by adding a salt to suppress plaque formation (see Patent Document 10).
However, these technologies are effective against periodontopathic biofilms but have sufficient bactericidal effect against cariogenic bacteria such as Streptococcus mutans in cariogenic biofilms. Was difficult to be demonstrated.

  In addition, although the composition which mix | blended polyoxyethylene hydrogenated castor oil with the mouthwash which mix | blended cetylpyridinium chloride and palmitoyl sarcosine sodium is illustrated in Example 2 of patent document 9, Example 10 of patent document 10, Since the mouthwash has a large number of carbon atoms in the palmitoyl group of palmitoyl sarcosine sodium, it cannot be said that the stability of the appearance is sufficiently secured due to the occurrence of orientation and scratches during low-temperature storage.

  Accordingly, development of a liquid oral composition that exhibits high bactericidal activity against cariogenic bacteria in cariogenic biofilms and has excellent appearance stability during low-temperature storage is desired.

JP 2006-117574 A JP 2006-117573 A Japanese Patent Laid-Open No. 2003-113059 JP-A-7-101842 JP-A-7-267840 JP 2006-0669909 A JP 2006-182663 A JP 2006-312588 A JP 2003-246717 A JP 2002-205929 A

  The present invention quickly penetrates the cariogenic biofilm in the oral cavity, exerts high bactericidal power against cariogenic bacteria, and suppresses the occurrence of orientation and scratches during low-temperature storage. It is an object of the present invention to provide a liquid oral composition excellent in appearance stability and a method for improving the bactericidal activity of a cationic bactericidal agent.

  As a result of intensive studies to achieve the above object, the present inventors have found that (A) cetylpyridinium chloride, (B) sodium lauroylsarcosine, and (C) ethylene oxide has an average added mole number of 40 to 100 moles. By blending oxyethylene hydrogenated castor oil at a specific ratio, the bactericidal agent quickly penetrates into the cariogenic biofilm in the oral cavity, effectively sterilizing cariogenic bacteria, and at low temperature storage It has been found that a liquid oral composition is obtained in which the occurrence of orientation and scratches is suppressed and the appearance stability is excellent.

  In this case, if the composition for liquid oral cavity contains a cationic bactericide having high bactericidal activity against cariogenic bacteria and an anionic surfactant that improves the permeability to biofilm, It is expected that the penetration sterilization power to biofilm will be enhanced. However, as a result of investigations by the present inventors, in this case, a complex is formed by the electrical interaction between the two, and not only the bactericidal power is not fully exhibited, but also the orientation and the negligence presumed to be a complex in low-temperature storage. Generated and appearance stability was impaired. Therefore, as a result of further investigation, the cationic fungicide cetylpyridinium chloride and lauroyl sarcosine sodium used as a fungicide and an anionic surfactant are used in combination, and the average added mole number of ethylene oxide is 40 to 40 By combining 100 moles of polyoxyethylene hydrogenated castor oil and using these components in a specific ratio, a complex formed by cetylpyridinium chloride and sodium lauroyl sarcosine is Immediately penetrates into the film and exhibits excellent bactericidal effect against cariogenic bacteria such as Streptococcus mutans, and also has a good appearance with little occurrence of dirt and scratches even when stored at low temperatures. It has been found that stability can be obtained. Such an effect of the present invention is that when cetylpyridinium chloride and sodium lauroyl sarcosine are blended, both components form a complex due to electrical interaction, and the activity of the bactericidal active site of each other is reduced. Since the solubility of the body is low, it precipitates as ORI and NIGORI in low-temperature storage, but by adding polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 mol to the above composite, The binding of the complex is weakened, the activity of each bactericidal active site is restored, the bactericidal power is fully exerted, and the complex can be solubilized by the surface-active action of the polyoxyethylene hydrogenated castor oil. It is believed that the complex originates from the ability to effectively penetrate cariogenic biofilms.

  Such effects of the present invention are, as is clear from the examples described later, cetylpyridinium chloride, sodium lauroyl sarcosine, and polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 mol. Can be achieved by combining them in specific proportions, using other disinfectants, using other anionic surfactants and nonionic surfactants in combination, or the proportion of each component However, even if it is outside the scope of the present invention, the object of the present invention is not achieved.

Accordingly, the present invention provides the following liquid oral composition and a method for improving the bactericidal activity of a cationic bactericide.
[I]
(A) Cetylpyridinium chloride 0.01 to 0.1% by mass
(B) Lauroyl sarcosine sodium 0.02-0.3 mass%
(C) Polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 mol is contained, and a mass ratio of (A) / (B) is 0.3 to 3, (C) / ((A ) + (B)) is a liquid oral composition, wherein the mass ratio is 1.0-20.
[II]
The liquid composition for oral cavity according to [I], which is prepared as a mouthwash.
[III]
A method for improving the bactericidal power of a cationic bactericide in a liquid oral composition,
(A) Cetylpyridinium chloride 0.01 to 0.1% by mass
(B) Lauroyl sarcosine sodium 0.02-0.3 mass%
(C) A polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 40 to 100 mol is blended, and the mass ratio of (A) / (B) is 0.3 to 3, (C) / (( A method of improving the bactericidal activity of the cationic bactericide, wherein the mass ratio of A) + (B)) is in the range of 1.0 to 20.

  The liquid buccal composition of the present invention and the method for improving the bactericidal power of a cationic bactericide have a bactericidal agent that quickly penetrates into the cariogenic biofilm and has an excellent bactericidal power against cariogenic bacteria. While exhibiting, the occurrence of orientation and scratches is suppressed even during low-temperature storage, the appearance stability is good, and it is effective in preventing caries.

  The liquid oral cavity composition of the present invention uses (A) cetylpyridinium chloride, (B) sodium lauroyl sarcosine, and (C) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 mol. It is characterized by.

  The component (A), cetylpyridinium chloride, is blended in an amount of 0.01 to 0.1% (mass%, the same applies hereinafter) with respect to the entire composition. It is preferable to set it as 0.05%. If the blending amount is less than 0.01%, the penetrability of the disinfectant into the biofilm may not be improved, and the high disinfecting power may not be exhibited. May be damaged.

  (B) Although the compounding quantity of lauroyl sarcosine sodium is 0.02-0.3% of the whole composition, 0.05-0.2% is especially preferable from the point of bactericidal power and appearance stability. If the blending amount is less than 0.02%, the penetrability of the bactericide into the biofilm may not be improved, and the high bactericidal power may not be sufficiently exhibited. May occur and appearance stability may be impaired.

  The mass ratio of (A) component / (B) component is 0.3-3, and it is preferable that it is 0.5-1 especially from the point of bactericidal power. If the (A) / (B) ratio is less than 0.3, the sterilizing power against the biofilm may not be satisfactorily exhibited. If it exceeds 3, the orientation stability and white turbidity may occur during low-temperature storage and the appearance stability may be impaired. is there.

  In the present invention, it is necessary to use (A) cetylpyridinium chloride and (B) sodium lauroyl sarcosine together in a specific ratio, whereby a complex of cetylpyridinium chloride and sodium lauroyl sarcosine is formed. It penetrates rapidly into the cariogenic biofilm and exhibits an excellent bactericidal effect against cariogenic bacteria such as Streptococcus mutans. The use of cetylpyridinium chloride or lauroyl sarcosine sodium alone cannot achieve the object of the present invention.

  (C) As polyoxyethylene hydrogenated castor oil, one or more polyoxyethylene hydrogenated castor oils having an average added mole number of ethylene oxide of 40 to 100 mol are blended. In this respect, the average added mole number of ethylene oxide is preferably 60 to 100. If the average number of added moles is less than 40 moles, appearance stability may be impaired during storage at low temperatures, or satisfactory sterilizing power may not be exhibited against cariogenic biofilms. Not commercially available.

  The blending amount of the polyoxyethylene hydrogenated castor oil as component (C) is preferably 0.1 to 3%, particularly preferably 0.2 to 2% of the whole composition. The appearance stability is impaired due to the occurrence of turbidity and white turbidity, and if it exceeds 3%, the taste may be deteriorated and the bactericidal power against cariogenic bacteria may not be sufficiently exhibited.

  Furthermore, in the present invention, in order to maintain appearance stability while maintaining penetrability of the bactericide into the cariogenic biofilm and bactericidal power against cariogenic bacteria, (C) component and (A (C) / ((A) + (B)), which is a ratio to the total content of the component (B) and the component (B), is 1.0 to 20, preferably 2 to 10 in terms of mass ratio. When the mass ratio is less than 1.0, that is, when the content of the component (C) is less than the total blending amount of the component (A) and the component (B), orientation and white turbidity occur during storage at low temperature, and the appearance stability is improved. If it is damaged and exceeds 20, the sterilizing power against cariogenic bacteria is not sufficiently exhibited.

  The liquid oral composition of the present invention can be prepared and applied as a type that can be used as it is without being diluted at the time of use, or as a concentrated type mouthwash or a mouth freshener that is diluted with water at the time of use. In addition to the above components, appropriate known components can be blended depending on the dosage form. For example, a solvent, a wetting agent, a thickener, a pH adjuster, an antiseptic, a sweetener, a fragrance, an active ingredient, a colorant, and the like can be blended. In addition, it is not necessary to mix | blend well-known surfactant other than the said essential component. Moreover, when preparing as a mouthwash, an abrasive | polishing agent does not need to mix | blend.

As the solvent, water is generally used, but an alcohol such as a polyhydric alcohol such as propylene glycol, ethylene glycol, or polyethylene glycol, or a lower alcohol such as ethanol can also be blended. The blending amount of the alcohol is usually 0 to 30%, particularly 1 to 10% of the whole composition.
In addition, the liquid oral composition of the present invention may not contain ethanol and substantially does not contain ethanol (that is, the ethanol content in the composition is 0.01% or less, particularly 0 to 0.00. (0001%) composition. Even with a composition that does not substantially contain ethanol, the bactericidal agent effectively penetrates into the cariogenic biofilm, can effectively sterilize cariogenic bacteria such as Streptococcus mutans, and can also be used at low temperature. And the occurrence of scratches can be suppressed.

As the wetting agent, sugar alcohols such as glycerin, sorbitol, malt, and lactit can be blended (the blending amount is usually 0 to 20%, particularly 1 to 9% of the whole composition).
As the thickener, xanthan gum, carrageenan, hydroxyethyl cellulose, sodium alginate, polyvinyl alcohol, sodium carboxymethyl cellulose and the like can be blended (the blending amount is usually 0 to 3%, particularly 0.01 to 0 of the whole composition). .5%).

Examples of the preservative include paraoxybenzoic acid esters such as methyl paraben, ethyl paraben, propyl paraben, and butyl paraben, and potassium sorbate.
As sweetening agents, xylitol, maltitol, saccharin, sodium saccharin, stevioside, aspartame and the like can be blended.

Perfumes include natural oils such as peppermint oil, spearmint oil, eucalyptus oil, wintergreen oil, clove oil, thyme oil, sage oil, cardamom oil, rosemary oil, marjoram oil, lemon oil, nutmeg oil, lavender oil, paracres oil, etc. Essential oils and l-menthol, l-carvone, cinnamic aldehyde, orange oil, anethole, 1,8-cineole, methyl salicylate, eugenol, thymol, linalool, limonene, menthone, menthyl acetate, citral, camphor, borneol, pinene, Perfume ingredients contained in the above natural essential oils such as spiranthol, ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl phenyl glycidate Benzaldehyde, vanillin, ethyl vanillin, furaneol, maltol, ethyl maltol, gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, ethylene glycol 1-menthyl carbonate Perfume ingredients such as apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee, brandy, yogurt 1 type or 2 types or more of compounding flavors, such as, can be mix | blended.
The blending amount of the fragrance is preferably 0.00001 to 3% in the composition, and can be blended within a range not impeding the effects of the present invention.

  Moreover, as an active ingredient, in addition to cetylpyridinium chloride, other active ingredients can be blended. Specifically, anti-inflammatory agents such as tranexamic acid and epsilon-aminocaproic acid, dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme, enzyme such as lytechenzyme, sodium fluoride, sodium monofluorophosphate, fluorine Fluorides such as stannous chloride, aluminum chlorohydroxy allantoin, allantoin, azulene, lysozyme chloride, ascorbic acid and other vitamin C, dihydrocholesterol, glycyrrhetinic salts, glycyrrhetinic acid, hydrocholesterol, chlorophyll, copper chlorophyllin sodium, thyme, ogon , Plant extracts such as clove, hamamelis, copper gluconate, caropeptide, sodium polyphosphate, water-soluble inorganic phosphate compound, polyvinylpyrrolidone, anticalculus agent, plaque prevention It can be added potassium nitrate, aluminum lactate and the like. In addition, the addition amount of these other active ingredients is a range which does not disturb the effect of this invention.

  As a colorant, a highly safe water-soluble pigment such as Blue No. 1, Green No. 3, Yellow No. 4, Red No. 105, and the like can be added.

  pH adjusters include phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid and carbonic acid and their potassium, sodium and ammonium salts, ribonucleic acid and its salts, sodium hydroxide, etc. One kind or two or more kinds selected can be used. In particular, it is preferable to use phosphoric acid and its sodium salt or citric acid and its sodium salt in combination. The liquid oral composition of the present invention preferably adjusts the pH at 25 ° C. to 5.5 to 8.0, and therefore, sodium dihydrogen phosphate and sodium monohydrogen phosphate as pH adjusters in the vicinity thereof, Or the combination of a citric acid and sodium citrate is suitable.

  As the container, PET (polyethylene terephthalate), glass, polypropylene, and polyethylene can be used, but PET or glass is preferable from the viewpoint of suppression of perfume adsorption.

EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an experiment example, an Example, and a comparative example, this invention is not restrict | limited by these Examples.
In the following examples, “%” means “% by mass” unless otherwise specified. Moreover, pH in a table | surface was measured using the pH meter (model number HM-30S) by Toa Denpa Kogyo immediately after preparation, and showed the value after 25 degreeC and 3 minutes. The parentheses in the polyoxyethylene hydrogenated castor oil indicate the average added mole number of ethylene oxide.

In addition, liquid oral compositions were prepared by using cetylpyridinium chloride (manufactured by Wako Pure Chemicals), sodium lauroyl sarcosine (manufactured by Kawaken Fine Chemical), polyoxyethylene (40) hydrogenated castor oil (manufactured by Nikko Chemicals), polyoxyethylene (60) hydrogenated castor oil (manufactured by Nikko Chemicals), polyoxyethylene (80) hydrogenated castor oil (manufactured by Nikko Chemicals), polyoxyethylene (100) hydrogenated castor oil (manufactured by Nippon Emulsion), ethanol (manufactured by Nippon Alcohol Sales), Citric acid (manufactured by Fuso Chemical), sodium citrate (manufactured by Fuso Chemical), sodium monohydrogen phosphate (manufactured by Taihei Chemical Sangyo), sodium dihydrogen phosphate (manufactured by Taihei Chemical Sangyo), xylitol (manufactured by Rocket Fleure), sorbitol (70%, manufactured by Towa Kasei), polyethylene glycol 400 (Daiichi Kogyo) ), Propylene glycol (manufactured by Asahi Glass), methylparaben (manufactured by API), ethylparaben (manufactured by API), butylparaben (manufactured by API), sodium saccharin (manufactured by Daito Chemical), glycerin (85%, manufactured by Sakamoto Pharmaceutical Co., Ltd.), fluoride Sodium (manufactured by Stella Chemifa), aspartame (manufactured by Ajinomoto), dextranase (manufactured by Daiichi Sankyo), and carrageenan (manufactured by Sanki) were used. Moreover, the fragrance | flavor of the composition shown in following Table 3 was used for the fragrance | flavor.
In addition to the components used in the above examples, triclosan (manufactured by Ciba Specialty Chemicals), sodium lauryl sulfate (manufactured by Toho Chemical Industry), palmitoyl sarcosine sodium (manufactured by Nikko Chemicals), polyoxyethylene (20) Hardened castor oil (manufactured by Nikko Chemicals) and polyoxyethylene (40) cetyl ether (manufactured by Nippon Emulsion) were used.

[Experimental Example 1]
Liquid oral compositions (mouthwashes) having the compositions shown in Tables 1 and 2 were prepared by a conventional method, and the following evaluation was performed using this as a sample.
Penetration effect of cetylpyridinium chloride into cariogenic biofilm 30g of trypticase soy broth (Difco) dissolved in 1L of purified water and 10g of sucrose (manufactured by Wako Pure Chemical) Was used. Place 2 mL of the culture solution inoculated with Streptococcus mutans ATCC 10449 strain as a cariogenic bacterium into a small glass test tube with a diameter of 13 mm x 150 mm and place it on a test tube stand (for Sanwa Kaken, 13 mm). And cultured for 18 hours under anaerobic conditions (5 vol% carbon dioxide gas, 95 vol% nitrogen) at 37 ° C. to form and attach a biofilm.
The culture solution in the test tube is discarded, and the formed biofilm is adjusted to pH 4.5 with a phosphate buffer solution (8.8 g of sodium chloride and 1.56 g of sodium dihydrogen phosphate dihydrate are dissolved in 1 L of purified water. (Adjusted to pH 4.5 with 1N aqueous sodium hydroxide solution) Washed once with 3 mL. After discarding the buffer solution, 0.5 mL of the sample shown in Tables 1 and 2 was added and immersed for 30 seconds. Thereafter, the sample solution was discarded, and the biofilm was dispersed by sonication with 2 mL of sterile physiological saline (manufactured by Nippon Seiki Seisakusho, US-300, 200 μA, 10 seconds). After adding 1 mL (internal standard substance solution) of 0.1 g of 4-octylphenyl salicylate (manufactured by Tokyo Chemical Industry) as an internal standard substance in 5 L of ethanol (99.5%) (manufactured by Kanto Chemical), The solution was filtered through a 45 μm membrane filter, and the filtrate was measured by liquid chromatography (sample injection amount: 40 μL), and the amount of cetylpyridinium chloride permeating into the biofilm was quantified.

The mobile phase of liquid chromatography was 75 vol% acetonitrile aqueous solution, pump: JASCO Corporation PU-980, sample introduction part: JASCO Corporation AS-950, detector: JASCO Corporation UV- 970 (measurement wavelength: set to 265 nm), recording device: System Instruments Co., Ltd. Chromatocoder 21J, column thermostatic chamber (set to 35 ° C.): JASCO Corporation CO-966, column: GL Science Co., Ltd. Inertsil ODS -2 (4 mmφ × 150 mm) was used. As a standard solution, 0.1 g of cetylpyridinium chloride (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 200 mL of mobile phase, and then 2 mL was collected from a solution diluted 125 times (volume ratio) with the mobile phase, and the above internal standard solution The liquid added with 1 mL was similarly measured by liquid chromatography (sample injection amount 40 μL).
From the peak area ratio of cetylpyridinium chloride / internal standard substance, the amount of cetylpyridinium chloride permeating into the biofilm was calculated using the following calculation formula, and the penetration effect of the bactericide was evaluated from the following criteria.
The results are shown in Tables 1 and 2.

Criteria for determining the penetration effect of bactericides ◎: the amount of cetylpyridinium chloride penetrated is 40 μg or more ○: the amount of cetylpyridinium chloride penetrated is 30 μg or more and less than 40 μg Δ: the amount of penetrated cetylpyridinium chloride is 20 μg or more and less than 30 μg Less than 20 μg of cetylpyridinium chloride

[Experiment 2]
Bactericidal effect against Streptococcus mutans bacteria in cariogenic biofilm 30 g Trypticase Soy Broth (Difco) as a culture solution was dissolved in 1 L purified water, and 10 g sucrose (Wako Pure Chemical Industries) was further dissolved. Things were used. Streptococcus mutans ATCC 10449 strain is inoculated as a cariogenic bacterium, and a hydroxyapatite (HA) plate (manufactured by Asahi Optical Co., Ltd.) having a diameter of 7 mm and a thickness of 3.5 mm is left in the culture solution at 37 ° C. under anaerobic conditions. Culturing with (5 vol% carbon dioxide gas, 95 vol% nitrogen) for 18 hours formed and attached a biofilm.

The HA plate to which the formed biofilm was attached was taken out from the culture solution. A phosphate buffer solution (8.8 g of sodium chloride and 1.56 g of sodium dihydrogen phosphate dihydrate) adjusted to pH 4.5 was dissolved in 1 L of purified water, and this HA plate was adjusted to pH 4 with 1 N aqueous sodium hydroxide solution. Washed in a beaker containing 100 mL.
Next, the HA plate is immersed in 10 mL of the sample shown in Tables 1 and 2 for 30 seconds, and further immersed in 2 mL of phosphate buffer adjusted to pH 4.5, and in a 37 ° C. constant temperature bath for 3 hours (Yamato Science) It was allowed to stand in IS400). Next, the HA plate to which the biofilm was attached was taken out and sonicated with 2 mL of sterile physiological saline (using Nippon Seiki Seisakusho, US-300, 200 μA, 10 seconds) to disperse the biofilm. The bacterial dispersion was diluted 10-fold, 100-fold, 1,000-fold, 10,000-fold, and 100,000-fold by volume ratio using sterile physiological saline. 45 g of Mittis Salivarius agar (Difco) And 50 g of sucrose (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 500 mL of purified water and then applied to an agar plate sterilized by heating and cultured at 37 ° C. for 3 days. The grown colonies were counted, and the number of remaining Streptococcus mutans bacteria (cfu) was calculated and determined according to the following criteria.
The results are shown in Tables 1 and 2.

Criteria for judging biofilm bactericidal effect ◎: The number of viable bacteria is less than 10 ⁶ ○: The number of viable bacteria is 10 ⁶ or more and less than 10 ⁷ △: The number of viable bacteria is 10 ⁷ or more and less than 10 ⁸ ×: The number of viable bacteria is 10 ⁸ or more

[Experiment 3]
Evaluation of Appearance Stability 450 mL of the sample shown in Tables 1 and 2 was filled into a colorless and transparent PET container (polyethylene terephthalate container, manufactured by Yoshino Kogyo Co., Ltd.) of 500 mL, and a 5 ° C. constant temperature bath (manufactured by Sanyo Electric, MPR-311). The appearance stability after storage for 1 month was visually determined according to the following criteria.
The results are shown in Tables 1 and 2.

Appearance stability evaluation standard A : There is no orientation and no scratch, and it is transparent.
○: Although very small suspended matter is recognized when shaken, it is transparent and has no problem.
(Triangle | delta): Slight ORI and Nigori are recognized.
X: Considerable orientation and negligence are recognized.

From the results of Tables 1 and 2, (A) Comparative Example 1 using triclosan widely used as a fungicide instead of cetylpyridinium chloride, (B) Comparison using sodium lauryl sulfate instead of lauroyl sarcosine sodium Example 2, Comparative Example 3 using polyoxyethylene (20) hydrogenated castor oil as a nonionic surfactant, Comparative Example 4 using polyoxyethylene (40) cetyl ether, Mass of components (A) / (B) Comparative Examples 5 and 6 in which the ratio is outside the range of 0.3 to 3, (A) Comparative Examples 7 and 8 in which the cetylpyridinium chloride content is outside the range of 0.01 to 0.1%, (B) Lauroyl Comparative Examples 9 and 10, where the sarcosine sodium content is outside the range of 0.02 to 0.3%, and the mass ratio of (C) / ((A) + (B)) is outside the range of 1.0 to 20 Some Comparative Examples 11 and 12 Or not caries inferior in permeability of the fungicide to the original bio-film in the sterilizing power is satisfaction exhibited, it was inferior to the appearance stability. Further, in Comparative Example 13 in which palmitoyl sarcosine sodium was blended in place of (B) lauroyl sarcosine sodium, orientation and scratches were generated during low-temperature storage, and the appearance stability was not sufficiently ensured.
Compared with these, the composition for liquid oral cavity of the present invention (Examples 1 to 16) effectively penetrates the cariogenic biofilm, exhibits high bactericidal power, and is stored at a low temperature. It has been confirmed that the occurrence of orientation and scratches in cans can be suppressed and the appearance stability is excellent.

なお、表中の部はいずれも質量部である（以下、同様。）。

In addition, all the parts in the table are parts by mass (the same applies hereinafter).

Claims (3)

(A) Cetylpyridinium chloride 0.01 to 0.1% by mass
(B) Lauroyl sarcosine sodium 0.02-0.3 mass%
(C) Polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 40 to 100 mol is contained, and a mass ratio of (A) / (B) is 0.3 to 3, (C) / ((A ) + (B)) is a liquid oral composition, wherein the mass ratio is 1.0-20.   The liquid oral cavity composition according to claim 1, which is prepared as a mouthwash. A method for improving the bactericidal power of a cationic bactericide in a liquid oral composition,
(A) Cetylpyridinium chloride 0.01 to 0.1% by mass
(B) Lauroyl sarcosine sodium 0.02-0.3 mass%
(C) A polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 40 to 100 mol is blended, and the mass ratio of (A) / (B) is 0.3 to 3, (C) / (( A method of improving the bactericidal activity of the cationic bactericide, wherein the mass ratio of A) + (B)) is in the range of 1.0 to 20.