JP5682283B2 - Liquid oral composition - Google Patents

Description

  The present invention is highly effective in suppressing the adhesion of plaque to the tooth surface and has a high bactericidal ability against mutans bacteria in plaque, is excellent in antiseptic power and appearance stability (no wrinkles), has low irritation, and has no bitterness. The present invention relates to a liquid oral composition that does not contain ethanol.

  Dental caries is caused by the acid produced in the plaque by the oral biofilm formed by Streptococcus mutans bacteria (hereinafter abbreviated as mutans), which are the causative bacteria in the oral cavity. It occurs when the teeth are decalcified. Therefore, in the field of liquid oral cavity composition as a means for preventing dental caries, means for sterilizing mutans bacteria in the oral cavity by blending various bactericides, and coating the tooth surface with specific drugs, etc. For example, a technique for suppressing the adhesion of oral bacteria and the formation of plaque is used.

  Cationic fungicides such as benzethonium chloride and cetylpyridinium chloride have a high bactericidal activity against mutans bacteria in the oral cavity and are easily adsorbed on the surface of oral tissues such as teeth and oral mucosa. Therefore, it is blended in many oral compositions.

  However, when the cationic bactericidal agent coexists with the nonionic surfactant, there is a problem that the bactericidal activity is significantly reduced by being taken into the active agent micelle. On the other hand, in the composition for liquid oral cavity, in order to ensure a feeling of use such as a refreshing feeling and a refreshing feeling and appearance stability over time, it is necessary to add a nonionic surfactant to ensure quality. However, when this is blended, there is a problem that the bactericidal effect of the cationic bactericidal agent decreases as described above.

  Therefore, as a technology that exerts a high plaque formation inhibitory effect even if a nonionic surfactant is added to the cationic bactericidal agent, by combining a cationic bactericidal agent, polyoxyethylene alkyl ether and a cationic polymer, Patent Document 1 proposes that plaque formation can be effectively prevented by suppressing adhesion of internal bacteria. However, this technique has a bitter taste derived from a cationic fungicide and is not sufficient in terms of palatability, and there is room for improvement in appearance stability.

In addition, by blending cationic fungicide, capsaicin, and nonionic surfactant with l-menthol or amino acid, a sufficient bactericidal effect can be obtained without deactivating the cationic fungicide, and a refreshing feeling can be obtained. Patent Documents 2 and 3 propose technologies that have improved palatability.
All of these techniques allow the blending (containment) of ethanol, but in recent years, there is a problem in that irritation caused by alcohol occurs while a mild feeling of use is required, and a non-alcohol composition is desired. There is a tendency.

However, in a composition in which ethanol is not blended, the preservative power is inferior to that in the case of blending with ethanol. Therefore, it is necessary to increase the preservative power by blending a preservative such as paraoxybenzoate. In addition, there is a method using a nonionic surfactant to ensure the appearance stability when paraoxybenzoic acid ester is blended in a composition not blended with ethanol, but for that purpose a necessary amount of nonionic surfactant is added. When it mix | blends, there existed a problem that the bactericidal power which a cationic disinfectant has decreased in the presence of a cationic disinfectant.
Although it is desirable to make the bactericidal activity effective even if a nonionic surfactant coexists with a cationic bactericidal agent in a composition that does not contain ethanol, it is difficult to ensure the appearance stability, antiseptic power and appearance stability There is a problem that it is difficult to ensure the sterilizing power at the same time.

  On the other hand, techniques for coating the tooth surface and inhibiting plaque formation include the method of coating the tooth surface with a cationic polymer, and the retention of non-cationic and cationic fungicides on the tooth surface. A method is known for improving the adhesion and suppressing the adhesion of oral bacteria to the tooth surface. Patent Document 4 proposes a technique for effectively preventing plaque formation by blending a hydroxyethylcellulose / dimethyldiallylammonium salt graft copolymer. However, this technique does not ensure the antiseptic power of the preparation, and further, since the sterilizing effect of mutans bacteria is not exhibited, it cannot be said that the effect of inhibiting the formation of plaque is sufficient. The sterilizing power against is not demonstrated.

In addition, it contains a cationic polymer and glucanase, and has a technology for suppressing the reattachment of plaque (Patent Document 5) and a glucanase-containing composition containing a cationic polymer and an organic acid or a water-soluble salt thereof. Although the technique (patent document 6) which blocks | prevents plaque formation effectively is proposed, these techniques do not mention the bactericidal power of the mutans bacteria in dental plaque, but are sufficient about such a bactericidal power. It cannot be said that it has a positive effect.
Patent Documents 4 to 6 are also technologies that allow ethanol to be blended.

JP 2001-139443 A JP 2001-322921 A JP 2004-115382 A JP 2001-064137 A JP 2001-163747 A JP 2001-316235 A

  Therefore, in a liquid oral composition substantially free of ethanol, the cationic bactericidal agent can effectively exert its bactericidal activity in the presence of a nonionic surfactant and can effectively suppress plaque formation. However, there is a demand for a technique that has a good feeling of use and that can maintain good preservative power and appearance stability of the preparation. However, the conventional techniques have the above-described problems, and it has been difficult to satisfy them.

  The present invention has been made in view of the above circumstances, and in a liquid oral composition not containing ethanol, it effectively suppresses the adhesion of plaque to the tooth surface and sufficiently sterilizes mutans bacteria in the plaque. And providing a liquid oral composition that can effectively suppress plaque formation, is excellent in preservative power and appearance stability (no wrinkles), has low irritation, has no bitterness, and has a good feeling in use. With the goal.

  As a result of intensive studies to achieve the above object, the present inventor has added (A) a cationic bactericidal agent and (B) a cationized cellulose to a liquid oral composition substantially free of ethanol. It is blended in a specific amount, and (C) propylene glycol, (D) polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100 mol, and (E) paraoxybenzoic acid ester (paraben) By blending, the effect of inhibiting the adhesion of plaque to the tooth surface and the sterilizing ability of mutans bacteria in the plaque is high, which can effectively suppress the formation of plaque, and also the antiseptic power and appearance stability of the preparation It was found that (excellent) was excellent, low irritation, no bitterness, and good usability (no bitterness, no irritation).

  More specifically, in the present invention, the composition of (A) a cationic bactericidal agent and (B) a cationized cellulose in a liquid composition that does not contain ethanol is used in an appropriate amount so that plaque on the tooth surface can be prevented. The adhesion suppressing effect is improved, and the mutans bacteria in the plaque can be effectively sterilized. By combining both effects, a high plaque formation suppressing effect can be exhibited. Furthermore, in such a low-stimulation composition that does not contain ethanol, paraben, which is an oil-soluble component that is usually difficult to dissolve unless ethanol is blended, is blended together with propylene glycol and the polyoxyethylene hydrogenated castor oil. Can be sufficiently dissolved, whereby the preservative power of the preparation is increased, and low irritation and good appearance stability (orientation suppression) can be secured. Therefore, according to the present invention, by blending the components (A) to (E), an excellent effect of suppressing plaque formation is exhibited in a liquid oral composition that does not contain ethanol, appearance stability, antiseptic power In addition, the feeling of use (no bitterness, no irritation) is also improved, and a liquid oral composition effective for preventing caries can be obtained.

Accordingly, the present invention provides the following liquid oral composition.
Claim 1:
In liquid oral cavity composition whose ethanol content is 100 ppm or less ,
(A) 0.01-0.1% by mass of a cationic fungicide ,
(B) 0.005 to 0.1% by mass of cationized cellulose and (C) 2 to 10% by mass of propylene glycol,
(D) 0.3 to 2% by mass of polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100 mol, and (E) 0.01 to 0.5% by mass of paraoxybenzoic acid ester
A composition for liquid oral cavity characterized by comprising
Claim 2:
(B) The liquid oral composition according to claim 1, wherein the cationized cellulose is hydroxyethyl cellulose dimethyl diallylammonium chloride.
Claim 3:
The composition for liquid oral cavity according to claim 1 or 2, which is transparent.

  According to the present invention, the effect of suppressing the adhesion of plaque to the tooth surface and the sterilizing ability of mutans bacteria in the plaque are high, the effect of suppressing the formation of plaque is excellent, and the antiseptic power and appearance stability of the preparation (the absence of orientation). It is possible to obtain a liquid oral composition containing no ethanol and having a low irritation, no bitterness and good usability, and this composition is effective in preventing caries.

  The liquid oral composition of the present invention comprises (A) a cationic bactericide, (B) cationized cellulose, (C) propylene glycol, and (D) polyoxyethylene having an average added mole number of ethylene oxide of 60 to 100 mol. It contains hydrogenated castor oil and (E) paraoxybenzoic acid ester, and is substantially free of ethanol.

  As the cationic fungicide of the component (A), one or more of cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride and the like can be used, and in particular, cetyl chloride in terms of bactericidal power and usability. Pyridinium and benzethonium chloride are preferred. The blending amount is 0.01 to 0.1% (mass%, the same applies hereinafter) of the whole composition in that it exerts the adhesion inhibitory effect of plaque on the tooth surface and the sterilizing ability of mutans bacteria in the plaque. In particular, it is preferably 0.02 to 0.05% in terms of bactericidal power and bitterness. If the blending amount is less than 0.01%, the plaque adhesion-inhibiting power and the sterilizing ability of mutans bacteria in plaque cannot be satisfactorily exhibited, and if it exceeds 0.1%, a bitter taste derived from a cationic fungicide is produced. .

  Examples of the cationized cellulose as the component (B) include those obtained by adding dimethyldiallylammonium, 2-hydroxy-3 (trimethylammonio) propyl or the like as a cationic group to a cellulose derivative. Examples of such cationized cellulose include hydroxyethylcellulose dimethyl diallylammonium chloride, O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethylcellulose, and the like, and the nitrogen content is 0.1 to 3%. Are preferred.

  Specifically, hydroxyethyl cellulose dimethyl diallylammonium chloride is obtained by graft polymerization of dimethyl diallylammonium salt to hydroxyethyl cellulose, and the viscosity of a 2% aqueous solution is 50 to 2,000 mPa · s (BH Brookfield viscometer, rotor). No. 2, 20 revolutions, 21 ° C. can be suitably used, for example, Cellcoat L-200 (2% aqueous solution viscosity: 35 to 350 mPa · s, BH type Brookfield viscometer, rotor No. manufactured by Akzo Nobel Co., Ltd. .2, 20 revolutions, 21 ° C., measurement time 1 minute), Cellcoat H-100 (2% aqueous solution viscosity: 500-2,750 mPa · s, BH type Brookfield viscometer, rotor No. 2, 20 revolutions, 21 ° C. , Measurement time 1 minute) and the like.

  As O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethylcellulose chloride, the viscosity can be measured with a 1% or 2% aqueous solution, and the viscosity is 5 to 800 mPa · s (BL type viscometer with a 2% aqueous solution). , Rotor No. 2, 30 rotations, 25 ° C., for example, Leogard KGP (2% aqueous solution viscosity: 5 to 50 mPa · s), Leogard G (2% aqueous solution viscosity: 100 to 600 mPas) manufactured by Lion Corporation S), Leoguard GP (2% aqueous solution 100-600 mPa · s), Leoguard LP (2% aqueous solution viscosity: 300-800 mPa · s), and 1% aqueous solution having a viscosity of 500-2,600 mPa · s (BH Brookfield) As a type viscometer, rotor No. 2, 20 rotation, 25 ° C.), for example, Leo Guard MG manufactured by Lion Corporation (1% aqueous solution viscosity: 500~1,200mPa · s), Reogado MLP (1% aqueous solution viscosity: 1,000~2,600mPa · s) and the like can be suitably used.

  Among these cationized celluloses, hydroxyethyl cellulose dimethyl diallylammonium chloride is particularly suitable because it is excellent in the ability to suppress the adhesion of plaque to the tooth surface and the sterilizing ability of mutans bacteria in the plaque.

  The blended amount of cationized cellulose is 0.005 to 0.1% of the whole composition in terms of the ability to suppress the adhesion of plaque to the tooth surface, the sterility of mutans bacteria in the plaque and the appearance stability. In particular, 0.01 to 0.05% is preferable in terms of plaque adhesion inhibiting power and bitterness. If it is less than 0.005%, the plaque adhesion inhibiting ability and the sterilizing ability of mutans bacteria in the plaque may not be satisfactorily exhibited. If it exceeds 0.1%, the occurrence of oliage impairs the appearance stability. Or a bitter taste derived from cationized cellulose.

  Component (C), propylene glycol, is an important component for maintaining the appearance stability while fully dissolving paraben, which is an oil-soluble component, in the preparation without adding ethanol, and exhibiting its antiseptic power. . The blending amount of propylene glycol is preferably 2 to 10%, more preferably 2 to 5%, based on the whole composition in terms of exerting these effects. If the blending amount is less than 2%, the solubility of paraben becomes insufficient, and the preservative power may not be satisfactorily exhibited or the appearance stability may be impaired. If it exceeds 10%, a bitter taste derived from propylene glycol is produced. There is a case.

  The component (D) polyoxyethylene hydrogenated castor oil is an ethylene oxide-based polymer that is capable of sufficiently exhibiting the adhesion inhibitory effect of plaque on the tooth surface and the sterilizing ability of mutans bacteria in the dental plaque and the appearance stability. It is necessary that the average added mole number is 60 to 100 moles. When the average added mole number of ethylene oxide is less than 60 moles, orientation may occur in a low-temperature storage product, and appearance stability (no orientation) may be impaired, and those exceeding 100 moles are generally not commercially available. .

  (D) The polyoxyethylene hydrogenated castor oil of component (D) can be blended with one or more kinds, and the blended amount exhibits the ability to suppress the adhesion of plaque to the tooth surface and the sterilizing ability of mutans bacteria in the plaque. And, from the viewpoint of appearance stability, 0.3 to 2% of the whole composition, particularly 0.5 to 1% is preferable in terms of exerting the sterilizing ability of mutans bacteria in dental plaque. If the blending amount is less than 0.3%, it may cause pits and the appearance stability may be impaired. If the blending amount exceeds 2%, the adhesion of dental plaque to the tooth surface and the sterilizing ability of mutans bacteria in the plaque will be reduced. You may not be able to demonstrate it.

  (E) As the paraoxybenzoic acid ester of the component, methyl paraoxybenzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate and the like can be used, and one or more of these can be used, and in particular, paraoxybenzoic acid. Methyl, ethyl paraoxybenzoate, especially methyl paraoxybenzoate are preferred.

  The compounding amount of the paraoxybenzoic acid ester is preferably 0.01 to 0.5%, particularly preferably 0.05 to 0.2%, less than 0.01% of the whole composition from the viewpoint of ensuring the antiseptic power of the liquid preparation. In some cases, the antiseptic power may not be sufficiently ensured, and if it exceeds 0.5%, the appearance stability (the absence of orientation) may be impaired, or a bitter taste derived from paraoxybenzoic acid ester may be produced.

  The liquid oral composition of the present invention is substantially free of ethanol. Here, “substantially free of ethanol” means that the amount of ethanol in the composition is preferably 100 ppm or less, more preferably 50 ppm or less, particularly preferably 10 ppm or less, based on the total composition. The value is 0 ppm. The liquid oral composition of the present invention contains no ethanol. However, since the raw material-derived ethanol may be contained in a small amount in the fragrance compounded in the composition, these reasons are taken into consideration. In addition to ethanol contained in trace amounts in perfume and the like, it does not contain ethanol.

  The composition for liquid oral cavity of the present invention can be prepared and applied as a mouthwash, liquid dentifrice, mouth freshener, concentrated mouthwash, and the like, in addition to the above components, appropriately known according to its dosage form Ingredients can be blended as required, for example, wetting agents other than (C) component, thickeners other than (B) component, sweeteners, fragrances, surfactants other than (D) component, (A) Active ingredients other than the ingredients, colorants, pH adjusters and the like can be blended.

  Examples of the wetting agent include sugar alcohols such as sorbitol, malt, and lactit, and examples of the polyhydric alcohol include glycerin, ethylene glycol, and polyethylene glycol. The blending amount of these wetting agents is preferably 2 to 20% of the entire composition including the component (C).

  Examples of the thickener include xanthan gum, carrageenan, hydroxyethyl cellulose, sodium alginate, polyvinyl alcohol, carboxymethyl cellulose and the like (the amount is usually 0 to 1%).

  As sweetening agents, xylitol, maltitol, saccharin, sodium saccharin, stevioside, aspartame and the like can be blended.

  Natural flavors 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 oil, 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 or more types of blended flavors such as the above can be used in the range of 0.00001 to 3% in the composition of the present invention as long as the effects of the present invention are not hindered.

As surfactant, amphoteric surfactant, anionic surfactant, and nonionic surfactant other than (D) component can be mix | blended.
Specific examples of amphoteric surfactants include betaine acetate-type amphoteric surfactants such as alkyldimethylaminoacetic acid betaines and fatty acid amidopropyldimethylaminoacetic acid betaines, and N-fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine salts. Such imidazoline type amphoteric surfactants can be used alone or in combination. A compounding quantity can be 0 to 5%.

  Anionic surfactants include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosine such as sodium N-lauroyl sarcosine, sodium N-myristoyl sarcosine, sodium dodecylbenzenesulfonate, hydrogenated coconut fatty acid N-acyl glutamate such as sodium monoglyceride monosulfate, sodium lauryl sulfoacetate, sodium N-palmitoyl glutamate, sodium N-methyl-N-acyl taurate, sodium N-methyl-N-acylalanine, sodium α-olefin sulfonate Is mentioned.

  Nonionic surfactants include sugar alcohol fatty acid esters such as sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, sucrose fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyethylene glycol fatty acid. Polyhydric alcohol fatty acid ester such as ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene copolymer, ether type or ester type surfactant such as polyoxyethylene alkylphenyl ether, fatty acid such as lauric acid diethanolamide Examples include alkanolamides. Examples of the cationic surfactant include alkyl ammonium and alkyl benzyl ammonium salts.

  (D) Surfactant other than component does not need to be blended, but when blended, the content of surfactant including component (D) is 0.3 to 3% of the total composition. Is preferred.

Also, as an active ingredient other than fungicides of component (A), sodium lauroyl sarcosinate, fungicides such as isopropyl methyl phenol, tranexamic acid, epsilon - anti-inflammatory agents such as aminocaproic acid, dextranase, amylase, protease, mutanase , Enzymes such as lysozyme, lytic enzyme, lytechenzyme, fluorides such as sodium fluoride, sodium monofluorophosphate, stannous fluoride, vitamin C such as aluminum chlorohydroxy allantoin, allantoin, azulene, lysozyme chloride, ascorbic acid , Dihydrocholesterol, glycyrrhetin salts, glycyrrhetinic acids, hydrocholesterol, chlorophyll, copper chlorophyllin sodium, thyme, hornon, clove, hamamelis and other plant extracts, gluconic acid Can Karopeputaido, sodium polyphosphate, water-soluble inorganic phosphoric acid compounds, polyvinylpyrrolidone, anti-tartar agents, anti-plaque agents, potassium nitrate, may be added to aluminum lactate and the like. In addition, the addition amount of these active ingredients can be made into the range which does not prevent 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.

  Examples of 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, and sodium hydroxide. Or a combination of phosphoric acid, citric acid and their sodium salts is particularly preferred. In this case, the liquid oral composition of the present invention preferably adjusts the pH at 25 ° C. to 5.5 to 8.0, and sodium dihydrogen phosphate and sodium monohydrogen phosphate as pH adjusting agents in the vicinity thereof. Alternatively, a combination of citric acid and sodium citrate can be used.

  As the container for the composition of the present invention, PET (polyethylene terephthalate), glass, polypropylene, and polyethylene can be used. From the viewpoint of suppressing the adsorption of the fragrance, the use of PET or glass is preferred.

  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 the following Example. In the following examples, “%” means “% by mass” unless otherwise specified. Moreover, pH in a table | surface measured using the pH meter (model number HM-30S) by Toa Denpa Kogyo immediately after adjustment, and showed the value after 25 degreeC and 3 minutes. The parentheses in the polyoxyethylene hydrogenated castor oil indicate the average number of moles of ethylene oxide added.

  In the preparation of the liquid oral composition in the following examples, cetylpyridinium chloride (manufactured by Wako Pure Chemical Industries, Ltd.), hydroxyethylcellulose dimethyl diallylammonium salt (Cellcoat L-200: manufactured by Akzo Novell Co., Ltd.), propylene glycol (manufactured by Asahi Glass Co., Ltd.) ), Polyoxyethylene (60) hydrogenated castor oil (manufactured by Nikko Chemicals), polyoxyethylene (100) hydrogenated castor oil (manufactured by Nippon Emulsion), methylparaben (manufactured by API), ethanol (manufactured by Nippon Alcohol Sales Co., Ltd.), citric acid (Manufactured by Fuso Chemical Co., Ltd.), sodium citrate (manufactured by Fuso Chemical Co., Ltd.), xylitol (manufactured by Rocket Fleure Co., Ltd.), sodium saccharin (manufactured by Daito Chemical Co., Ltd.), glycerin (85%, manufactured by Sakamoto Pharmaceutical Co., Ltd.), sodium lauroyl sarcosine ( Kawaken Fine Chemical Co., Ltd.) was used. Moreover, the fragrance | flavor composition of the composition shown in following Table 4 was used for the fragrance | flavor. Furthermore, polyoxyethylene (40) hydrogenated castor oil (manufactured by Nikko Chemicals Co., Ltd.) was used in addition to the components used in the above Examples for the preparation of Comparative Examples.

[Experimental Example 1]
Liquid oral compositions (mouth washes) having the compositions shown in Tables 1 to 3 were prepared by a conventional method, and the effect of inhibiting the adhesion of plaque to the tooth surface was evaluated by the following method. The results are shown in Tables 1-3.
Evaluation method of plaque adhesion suppression effect:
Each 2 mL of liquid oral composition was placed in a 24-well multiplate, and three mirror-polished hydroxyapatite plates (radius 0.35 cm × height 0.35 cm or less, referred to as HAP plate) for 30 seconds. Soaked.
In a 24-well multiplate, add 2 mL of buffer solution ^{* 1 in} which Streptococcus mutans 10449 strain is dispersed so that the turbidity at a wavelength of 660 nm is 0.35, and immerse the above HAP plates three by three. And left to stand at 37 ° C. for 2 hours to allow the bacteria to adhere. Next, the HAP plate was taken out and washed with sterilized water, and then the HAP plates washed in ² mL of liquid medium ^{* 2} were immersed in 3 pieces at 37 ° C. for 8 hours to culture adherent bacteria. After washing with distilled water, it was stained with a plaque staining solution, the a value was measured with a color difference meter, and the average value of the three sheets was calculated. The evaluation criteria are as follows.

Evaluation criteria for plaque adhesion control:
A: Average value of a value is less than 5 ○: Average value of a value is 5 or more and less than 7.5 Δ: Average value of a value is 7.5 or more and less than 10 ×: Average value of a value is 10 or more

* 1: Composition of buffer solution 3.37 g of potassium chloride (KCl), 0.14 g of potassium dihydrogen phosphate (KH ₂ PO ₄ ), 0.11 g of calcium chloride (CaCl ₂ ), 0.02 g of magnesium chloride (MgCl ₂ ) Was dissolved in 800 mL of purified water, pH was adjusted to 7.0 with potassium hydroxide (KOH), and the volume was adjusted to 1 L with purified water.
* 2: Composition of liquid medium 100 mL of purified water was dissolved in 3 g of Tryptic Soy Broth and 0.5 g of Sucrose.

The components used are as follows.
Potassium chloride: Kanto Chemical Co., Ltd. reagent special grade potassium dihydrogen phosphate: Kanto Chemical Co., Ltd. reagent special grade calcium chloride: Kanto Chemical Co., Ltd. reagent special grade magnesium chloride: Kanto Chemical Co., Ltd. reagent special grade potassium hydroxide: Kanto Chemical Co., Ltd. reagent special grade TSB Medium: Becton Dickinson's Sucrose: Kanto Chemical Co., Ltd. reagent grade color difference meter:
Spectrophotometer SE 2000 manufactured by NIPPON DENSHOKU

[Experiment 2]
About the composition for liquid oral cavity of the composition shown to Tables 1-3, the mutans bacteria bactericidal power in plaque was evaluated by the following method. The results are shown in Tables 1-3.
Evaluation method of sterilizing ability of mutans bacteria in dental plaque:
Actinomyces naeslundii T14V strain, Fusobacterium nucleatum ATCC10953 strain, Porphyromonas gingivalis (Porphylomonas gingivalis) (Porphyromonas gingivalis) ) 5 mg / L hemin (manufactured by Sigma Aldrich) and 1 mg / L vitamin K (Wako Pure Chemical Industries, Ltd.) obtained by autoclaving 40 μL of each bacterial solution of W50 strain, Streptococcus mutans ATCC25175 strain at 121 ° C. for 15 minutes, respectively Todd Hewitt Broth (Becton and Dicki) It was added son, Inc.) (in THBHM ^* 3) 4mL, overnight anaerobically cultured at 37 ° C. (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% of hydrogen) was. After culture, 300 μL was collected from each bacterial solution (4 types), added to 30 mL of THBHM, and further cultured overnight. After re-culture, each bacterial solution was centrifuged (10,000 rpm, 10 min), and the supernatant was discarded. A basal medium mucin medium (BMM ^{* 4} ) autoclaved at 121 ° C. for 15 minutes was added to each sediment (bacteria) and resuspended, followed by a culture tank (diameter 140 mm × height 200 mm) containing 1,000 mL of BMM in advance. And inoculating so that the number of each bacterium is 1 × 10 ⁷ cells / mL, and stirring with a stirrer (diameter 10 mm × length 51 mm) (rotating at about 100 rpm) at 37 ° C. under anaerobic conditions The cells were cultured overnight (95 vol% nitrogen, 5 vol% carbon dioxide) overnight. Thereafter, BMM was supplied at a rate of 100 mL / h, and the culture solution was discharged at the same rate. The culture medium discharged from the culture tank was continuously supplied to another culture tank (diameter 90 mm × height 190 mm) whose liquid volume was maintained at 300 mL.
A hydroxyapatite disk (diameter 7 mm × height 3.5 mm) as an attachment carrier was attached to a rotating disk (rotated at about 80 rpm) in the culture tank, and dental plaque was artificially formed on the surface thereof.

The culture by the above method was carried out for 14 days, and the following treatment was carried out for the latter 7 days. That is, 3 times a day, the hydroxyapatite disk to which plaque adheres is taken out of the culture tank, each is transferred to each petri dish (diameter 25 mm × height 14 mm), and the test composition 5 g (Example and Comparative Example) is used for 30 seconds. Soaked. Then, after washing 3 times with 5 g of physiological saline, it was returned to the culture tank again. The same operation was performed seven times.
At the end of culture, the plaque was transferred to a test tube (diameter 13 mm × 100 mm) to which 4 mL of physiological saline was added in order to evaluate the bactericidal activity of mutans bacteria in the plaque of the test composition. Immediately after sonication (200 μA output for 10 seconds) and serial dilution (10-fold dilution in 6 stages), each bacterial solution was smeared on a bacitracin-added Mitis-Salivarius agar plate medium ^{* 5} prepared by a conventional method. The plate medium was anaerobically cultured (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) until colonies could be confirmed with the naked eye. After counting the number of colonies in each plate medium, the number of viable bacteria was calculated. Further, as a control, the same treatment was performed using purified water instead of the test composition, and the number of viable bacteria in the plaque was calculated. The ratio of the viable count of those treated with each test composition when the viable count of those treated with purified water was taken as 100% was measured and indicated by the following criteria.

Evaluation criteria:
◎: Number of remaining viable bacteria less than 1% ○: Number of remaining viable bacteria 1% or more and less than 10% Δ: Number of remaining viable bacteria 10% or more and less than 50% ×: Number of remaining viable bacteria 50% or more

* 3: THBHM composition (expressed in mass per liter)
Todd Hewitt Broth (Becton and Dickinson):
30g / L
Hemin (Sigma Aldrich): 5mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries): 1mg / L
Purified water: remaining
(Measured up so that the total amount was 1 L.)

* 4: BMM composition (expressed in mass per liter)
Proteose peptone (Becton and Dickinson):
2g / L
Tryptone (Becton and Dickinson): 1g / L
Mucin (Sigma Aldrich): 2.5g / L
Hemin (Sigma Aldrich): 1mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries, Ltd.): 0.2mg / L
KCl (manufactured by Wako Pure Chemical Industries): 0.5g / L
Cysteine (manufactured by Wako Pure Chemical Industries): 0.1 g / L
Purified water: remaining
(Measured up so that the total amount was 1 L.)

* 5: Composition of Bacitracin-added Mitis-Salivarius agar plate medium (composition in 1 liter)
Mitis-Salivarius Agar
(Becton and Dickinson) 90g / L
Bacitracin (Sigma Aldrich) 200U / L
(Bacitracin was prepared in advance as an aqueous solution having a 1,000-fold concentration of 200,000 / L, and after MS agar was autoclaved, it was cooled to about 50 ° C. and added to 1/1000 of the medium.)

[Experiment 3]
About the liquid oral composition of the composition shown to Tables 1-3, antiseptic | preservative power was evaluated by the following method. The results are shown in Tables 1-3.
Method for evaluating antiseptic power:
As test bacteria, frozen intestinal bacteria and frozen Pseudomonas aeruginosa were used. These were all obtained from the National Institute of Technology and Evaluation (NITE). Each of these test bacteria was cultured in a medium, and a bacterial suspension was prepared so as to be about 10 ⁸ to 10 ⁹ cells / mL.
0.2 mL of the bacterial suspension was added to 20 g of the evaluation sample and mixed well to prepare an evaluation sample solution, which was then stored in the dark at 20 ° C.
Next, after 1 day, 4 days, 7 days, 14 days, and 28 days after storage, 1 g is aseptically collected from the sample solution for evaluation, and lecithin / polysorbate 80 added soybean / casein / digest liquid medium ^{* 6} 9 mL Each was diluted and mixed. 1 mL and 0.1 mL of the solution obtained by dilution and mixing were each taken in a petri dish and mixed with lecithin / polysorbate 80-added soybean / casein / digest agar medium. Culture was performed at 30 ° C. for 4 days, and the number of surviving bacteria in the sample was measured.
The determination was made according to the following criteria based on the number of days until the added bacteria were below the detection limit (10 / g or less).

Evaluation criteria:
A: Within 7 days, the added bacteria died to below the detection limit (10 cells / g or less).
○: Within 8 to 14 days, the added bacteria died to below the detection limit (10 cells / g or less).
Δ: Within 15 to 28 days, the added bacteria died to below the detection limit (10 cells / g or less).
X: It did not die to the detection limit or less (10 pieces / g or less) at 28 days.

* 6: Lecithin / polysorbate 80 soy bean / casein / digest liquid medium 38 g of lecithin / polysorbate 80 soy bean / casein / digest liquid medium (manufactured by Nippon Pharmaceutical Co., Ltd.) was added to 1 L of purified water and shaken well. The solution was stirred for several minutes to dissolve, dispensed into a container, and then autoclaved at 121 ° C. for 15-20 minutes. After sterilization, the mixture was thoroughly shaken with caution to make the polysorbate layer precipitated on the bottom of the container uniform.

[Experimental Example 4]
About the liquid oral cavity composition of the composition shown to Tables 1-3, the external appearance stability was evaluated by the following method. The results are shown in Tables 1-3.
Appearance stability evaluation method:
A sample (liquid oral composition) is filled into a colorless transparent PET container (manufactured by Yoshino Kogyo Co., Ltd.) having a full injection volume of 500 mL, and stored in a 5 ° C. constant temperature bath (manufactured by Sanyo Electric Co., Ltd., MPR-311) for one month. The appearance stability was visually determined according to the following criteria.
Appearance stability evaluation criteria:
A: There is no orientation or 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.

[Experimental Example 5]
About the liquid oral composition of the composition shown to Tables 1-3, irritation was evaluated by the following method. The results are shown in Tables 1-3.
Evaluation of lack of stimulation:
A sample containing 10 mL was rinsed for 30 seconds, and the absence of irritation after the mouthwash was evaluated in the following four stages. The average score of 10 people was indicated by ◎, ○, Δ, × according to the following criteria. .
Criteria for non-irritating after mouthwash:
4 points: There was no irritation.
3 points: There was almost no irritation.
2 points: Slight irritation was observed.
1 point: There was considerable stimulation.
Evaluation criteria for lack of stimulation:
◎: Average point 3.5 points or more and 4.0 points or less ○: Average point 3.0 points or more and less than 3.5 points △: Average point 2.0 points or more and less than 3.0 points ×: Average point 2.0 points Less than

[Experimental Example 6]
About the liquid oral composition of the composition shown to Tables 1-3, the following method evaluated the bitterness-lessness. The results are shown in Tables 1-3.
Evaluation method of bitterness:
4 points: There was no bitterness.
3 points: Little bitterness.
2 points: Bitterness was slightly to slightly.
1 point: There was considerable bitterness.
Evaluation criteria for lack of bitterness:
◎: Average point 3.5 points or more and 4.0 points or less ○: Average point 3.0 points or more and less than 3.5 points △: Average point 2.0 points or more and less than 3.0 points ×: Average point 2.0 points Less than

  A prescription example is shown below. The raw materials used are the same as described above, and the liquid oral compositions of these prescription examples all have a high effect of suppressing the adhesion of plaque to the tooth surface and the sterilizing ability of mutans bacteria in the plaque, It was excellent in antiseptic power and appearance stability, low irritation, no bitterness, and good usability.

[Prescription Example 1]
Benzalkonium chloride 0.01%
Hydroxyethylcellulose dimethyl diallylammonium chloride 0.01%
Propylene glycol 5%
Polyoxyethylene hardened (100) castor oil 0.5%
Methyl paraoxybenzoate 0.05%
Citric acid 0.05%
Sodium citrate 0.3%
Glycerin 3%
Saccharin sodium 0.003%
Fragrance (A) 0.3%
Purified water balance
Total 100.0%

[Prescription Example 2]
Benzethonium chloride 0.01%
Hydroxyethylcellulose dimethyl diallylammonium chloride 0.05%
Propylene glycol 3%
Polyoxyethylene hardened (100) castor oil 0.6%
Ethyl paraoxybenzoate 0.05%
Citric acid 0.05%
Sodium citrate 0.3%
Xylitol 5%
Glycerin 3%
Fragrance (B) 0.3%
Purified water balance
Total 100.0%

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)

In liquid oral cavity composition whose ethanol content is 100 ppm or less ,
(A) 0.01-0.1% by mass of a cationic fungicide ,
(B) 0.005 to 0.1% by mass of cationized cellulose and (C) 2 to 10% by mass of propylene glycol,
(D) 0.3 to 2% by mass of polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 60 to 100 mol, and
(E) 0.01-0.5 mass% of paraoxybenzoic acid ester
A composition for liquid oral cavity characterized by comprising   (B) The liquid oral composition according to claim 1, wherein the cationized cellulose is hydroxyethyl cellulose dimethyl diallylammonium chloride. The composition for liquid oral cavity according to claim 1 or 2, which is transparent.