WO2012132747A1

WO2012132747A1 - Liquid composition for oral cavity and method for stable addition of components to composition

Info

Publication number: WO2012132747A1
Application number: PCT/JP2012/055170
Authority: WO
Inventors: 尚子川口
Original assignee: ライオン株式会社
Priority date: 2011-03-25
Filing date: 2012-03-01
Publication date: 2012-10-04
Also published as: KR101936969B1; CN103458864B; JP5853387B2; KR20140007406A; CN103458864A; MY164603A; JP2012201632A

Abstract

Provided is a liquid composition for the oral cavity, which is excellent in terms of a plaque deposition-inhibiting effect and bactericidal effect against the Streptococcus mutans in plaque; has improved stability of appearance and is palatable; and is free of ethanol. The liquid composition for the oral cavity is characterized in that (A) a cationic bactericide and (B) a hydroxyethyl cellulose dimethyl diallylammonium chloride are added to a liquid composition for the oral cavity that is substantially ethanol-free; (C) anethole is also used at a mass ratio of component (C)/[component (A) + component (B)] that is within a range of 0.1 to 10; and (D) a polyhydric alcohol and/or (E) nonionic surfactant are added. Also provided is a method for the stable addition of components (A) and (B) to the composition whereby components (A) and (B) are added to the liquid composition for the oral cavity, component (C) is also used within a range of (C)/[(A)+(B)] of 0.1 to 10; and components (D) and/or (E) are added.

Description

Liquid oral composition and method for stabilizing and blending ingredients into the composition

The present invention has an excellent effect of suppressing the adhesion of dental plaque to the tooth surface and the ability to sterilize mutans bacteria in dental plaque, and has improved appearance stability (no lip) and good palatability, and does not contain ethanol. The present invention relates to a liquid oral composition and a method for stabilizing and blending ingredients into the composition.

Plaque suppression is important for the prevention of periodontal disease and caries, and oral compositions containing a bactericidal agent are widely used for the purpose of plaque suppression. Among these fungicides, cationic fungicides are widely used because they have bactericidal effects on oral bacteria, plaque-inhibiting effects, and gingivitis improving effects. Further, hydroxyethyl cellulose dimethyl diallylammonium chloride has a property of being easily adsorbed on the tooth surface, and a liquid oral composition capable of effectively suppressing plaque formation using this is disclosed in Patent Document 1 (Japanese Patent Laid-Open No. 2001-2001). No. 64137). Furthermore, it is known that the effect of inhibiting the adhesion of plaque is synergistically improved by combining a cationic polymer with a cationic fungicide such as cetylpyridinium chloride (CPC) (Patent Document 2; No. 2000-34213). The combined use of hydroxyethylcellulose dimethyldiallylammonium chloride and a cationic fungicide is known, and various related techniques have been proposed (Patent Document 3; JP 2001-139442 A, Patent Document 4; JP 2001-2001). 139443).

All of the prior arts allow the blending of ethanol. However, in recent years, there is a problem that alcohol irritation occurs in a demand for low irritation, and a non-alcohol composition tends to be desired. there were.

However, in the case where ethanol is not blended, it is difficult to ensure the stability of appearance with a composition containing a cationic bactericide and hydroxyethylcellulose dimethyl diallylammonium chloride, and it is difficult to simultaneously ensure the absence of irritation and the stability of appearance over time. There was a problem of being. Furthermore, astringent taste, bitter taste, and off-flavor derived from the cationic fungicide and hydroxyethyl cellulose dimethyl diallylammonium chloride may occur, making it difficult to achieve both the effects of both components and the preference of the preparation.

JP 2001-64137 A JP 2000-34213 A JP 2001-139442 A JP 2001-139443 A

Therefore, a technology that stably mixes a cationic bactericide and hydroxyethyl cellulose dimethyl diallylammonium chloride into a liquid formulation that does not contain ethanol, ensures appearance stability, and achieves both the effects of both components and the preference of the formulation. Is desired.
The present invention has been made in view of the above circumstances, and is excellent in anti-plaque adhesion and sterilizing ability against mutans bacteria in plaque, and has improved appearance stability and good palatability. An object of the present invention is to provide a liquid oral composition that does not contain it, and a method for stabilizing and blending ingredients into the composition.

As a result of intensive studies to achieve the above object, the present inventor has formulated (A) a cationic bactericidal agent and (B) hydroxyethyl cellulose dimethyl diallylammonium chloride into a liquid oral composition substantially free of ethanol. In addition, (C) Anethole is blended such that (C) component / [(A) component + (B) component] is in a mass ratio of 0.1 to 10, and (D) polyhydric alcohol and / or ( E) By adding a nonionic surfactant, it has excellent anti-plaque effect on plaque adhesion and sterilizing ability of mutans bacteria in plaque, and also suppresses the occurrence of orientation of the preparation and improves the appearance stability over time. It has been found that a liquid preparation with high appearance stability and good palatability can be obtained, and the present invention has been made.

The present applicant has formulated a liquid oral composition containing substantially no ethanol, a cationic disinfectant and a cationized cellulose, and a blend of propylene glycol, polyoxyethylene hydrogenated castor oil, and paraoxybenzoic acid ester. Japanese Patent Application No. 2010-280009 (Japanese Patent Application No. 2011-148770) shows that the composition for oral cavity is excellent in the effect of suppressing the adhesion of plaque and the sterilizing ability of mutans bacteria in the plaque, as well as the antiseptic power and appearance stability of the preparation. Proposed). This composition for liquid oral cavity is excellent in appearance stability (no tilt) after storage at 5 ° C. for 1 month. On the other hand, when the present inventors further examined, in a liquid oral composition containing no ethanol, it is difficult to stably maintain the appearance of the preparation when a cationic bactericide and cationized cellulose are blended. In particular, it was found that when stored at a high temperature for a long period of time, the orientation was lowered and the appearance stability was lowered, and studies were made on a technique capable of further stabilizing the cationic fungicide and the cationized cellulose. As a result, anethole is surprisingly effective as a stabilizer, and the oral over time when a cationic bactericide and hydroxyethylcellulose dimethyldiallylammonium chloride are used in combination with a liquid oral composition that does not contain ethanol. And by contributing to the improvement of appearance stability, it is possible to appropriately add anethole to a composition in which both the above components are used in combination, and to add a polyhydric alcohol and / or a nonionic surfactant. The present inventors have found that appearance stability can be ensured, and that the excellent effects of both components can be exhibited while suppressing astringency, bitterness, and off-flavor derived from these components while maintaining good palatability.

Anethole is known to be used as a fragrance in oral compositions, but is effective for stabilizing and blending cationic bactericides and hydroxyethylcellulose dimethyl diallylammonium chloride into liquid oral compositions that do not contain ethanol, It is a new finding of the present inventor that high appearance stability with almost no orientation can be secured even after storage at 50 ° C. for 1 month, and that a liquid preparation having the above-mentioned special effects can be obtained.

Accordingly, the present invention provides the following liquid oral composition and a method for stabilizing and blending ingredients into the composition.
[I]
A liquid oral composition substantially free of ethanol is blended with (A) a cationic fungicide and (B) hydroxyethyl cellulose dimethyl diallylammonium chloride, and (C) anethole is added to component (C) / [(A). Component + (B) component] is used in a mass ratio of 0.1 to 10, and (D) a polyhydric alcohol and / or (E) a nonionic surfactant is blended. Liquid oral composition.
[II]
A liquid oral composition substantially free of ethanol is blended with (A) a cationic fungicide and (B) hydroxyethyl cellulose dimethyl diallylammonium chloride, and (C) anethole is added to component (C) / [(A). Component + (B) component] is used in a range of 0.1 to 10 as a mass ratio, and (D) a polyhydric alcohol and / or (E) a nonionic surfactant is blended, A method of stabilizing and blending the components (A) and (B) in the composition.

According to the present invention, a liquid oral composition substantially free of ethanol, having excellent anti-plaque adhesion effect and sterilizing ability of mutans bacteria in dental plaque, improved appearance stability and good palatability Can be provided.

Hereinafter, the present invention will be described in further detail. The liquid oral composition of the present invention comprises (A) a cationic fungicide, (B) hydroxyethylcellulose dimethyl diallylammonium chloride, (C) anethole, (D) a polyhydric alcohol and / or (E) a nonionic surfactant. Contains agents.

The cationic fungicide of the component (A) is an active ingredient for suppressing adhesion of plaque to the tooth surface and sterilizing mutans bacteria in the plaque. Specific examples include cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride. One of these can be used alone, or two or more can be used in combination. Of these, cetylpyridinium chloride is preferred in terms of bactericidal power, handling properties and usability.

The blending amount of the cationic fungicide as component (A) is 0.01 to 0.1% (mass) of the whole composition from the viewpoint of suppressing adhesion of plaque to the tooth surface and sterilizing ability of mutans bacteria in the plaque. %. The same shall apply hereinafter.), In particular, 0.02 to 0.05% is preferable. If it is less than 0.01%, the effect of suppressing the adhesion of plaque to the tooth surface and the sterilizing ability of mutans bacteria in the plaque may not be satisfactorily exhibited. If it exceeds 0.1%, astringent taste, bitter taste, and off-flavor derived from the cationic fungicide may occur.

(B) Hydroxyethyl cellulose dimethyl diallylammonium chloride is a cationic polymer, and is blended as an active ingredient for suppressing adhesion of plaque to the tooth surface. By blending the component (B) together with the cationic germicide of the component (A), the effect of suppressing the adhesion of plaque to the tooth surface can be improved, and the mutans bacteria in the plaque can be effectively sterilized, By combining both effects, a high plaque formation inhibitory effect is achieved.

A commercially available product can be used as hydroxyethyl cellulose dimethyl diallylammonium chloride, and examples thereof include the following.
・ Cell coat L-200 (manufactured by Akzo Nobel):
Nitrogen content 0.1-3%, 2% aqueous solution viscosity 30-3,000 mPa · s (BH Brookfield viscometer, rotor No. 2, 20 revolutions, 21 ° C., measurement time 1 minute)
・ Cell coat H-100 (manufactured by Akzo Nobel):
Nitrogen content is 1.0%, 2% aqueous solution viscosity is 500-2,750 mPa · s (BH type Brookfield viscometer, rotor No. 2, 20 revolutions, 21 ° C., measuring time 1 minute)

The blending amount of component (B) hydroxyethylcellulose dimethyl diallylammonium chloride is preferably 0.005 to 0.5%, particularly 0.01 to 0.05% of the total composition. If it is less than 0.005%, the plaque adhesion inhibiting effect may not be satisfactorily exhibited. If it exceeds 0.5%, orientation may occur and appearance stability (no orientation) may be impaired, and astringency, bitterness, and off-taste derived therefrom may occur, resulting in a decrease in the feeling of use.

Component (C) Anethole is blended as a stabilizer. By blending Anethole, orientation can be suppressed over time and appearance stability can be improved, and the feeling of use (astringency, bitterness, tastelessness) can also be improved.
(C) The blending amount of anethole is preferably 0.01 to 0.2%, particularly preferably 0.01 to 0.1% of the whole composition. If the blending amount is less than 0.01%, the appearance stability (no tilt) may not be satisfactorily improved. In addition, the feeling of use (astringency, bitterness, tastelessness) may not be improved. If it exceeds 0.2%, the appearance stability (no tilt) may be impaired, and the feeling of use (taste) may be reduced.

In the present invention, component (C) / [component (A) + component (B)] is 0.1 to 10, and preferably 0.2 to 2, as a mass ratio. (C) By mix | blending component in the said ratio with respect to (A) and (B) component, generation | occurrence | production of the orientation by the mixing | blending of (A) and (B) component can be suppressed, and the external appearance stability of a formulation can be improved, Further, the feeling of use can be improved. If it is less than 0.1, astringency, bitterness, nasty taste, etc. occur, and it is impossible to suppress the orientation while maintaining good palatability, and if it exceeds 10, the appearance stability (no orientation) is impaired.

In this invention, (A) and (B) component can be stabilized and mix | blended by mix | blending (D) polyhydric alcohol and / or (E) nonionic surfactant with (C) anethole, and appearance stability Can be increased. (D) and (E) component may mix | blend either or (D) and (E) component may be used together from the point of an effect expression.

Examples of the (D) polyhydric alcohol include propylene glycol, glycerin, xylitol, sorbit, polyethylene glycol such as ethylene glycol and polyethylene glycol 400, polypropylene glycol, malt, lactit, and the like. A mixture of more than one can be used.
When blending the component (D) polyhydric alcohol, it is preferable to add 2 to 20%, particularly 2 to 15% of the total composition. If it is less than 2%, the appearance stability (no tilt) may not be satisfactorily improved. If it exceeds 20%, an off-taste derived from a polyhydric alcohol is produced, and the feeling of use (astringency, bitterness, lack of off-taste) may be impaired.

(E) As a nonionic surfactant, what is normally mix | blended with the composition for oral cavity can be used, However, Polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, decaglycerin mono fatty acid ester, etc. are used suitably. it can. For example, polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 60 to 100 moles, an alkyl group having 16 (cetyl) to 18 (stearyl) carbon atoms and an average addition mole number of ethylene oxide of 20 to 40 moles. Polyoxyethylene alkyl ether, fatty acid having 12 (lauric acid) to 18 (stearic acid), in particular 12 to 14 (myristic acid), decaglycerin monofatty acid ester, etc., one or two selected from these The above can be blended. Among them, polyoxyethylene hydrogenated castor oil is preferable from the viewpoint of sufficiently exerting the adhesion inhibitory effect of plaque on the tooth surface and the sterilizing ability of mutans bacteria in the plaque, and the appearance stability (no orientation), In particular, ethylene oxide having an average added mole number of 60 to 100 moles is preferred. When the average added mole number of ethylene oxide is less than 60 moles, orientation may occur in a 50 ° C. stored product and appearance stability (no orientation) may be impaired, and those exceeding 100 moles are generally not commercially available.

Specifically, the following commercially available products can be used.
・ Polyoxyethylene hydrogenated castor oil NIKKOL HCO system manufactured by Nikko Chemicals, Emalex HC system manufactured by Nihon Emulsion Co., Ltd., UNIOX HC system manufactured by NOF Corporation, etc. ・ Polyoxyethylene alkyl ether Emalex manufactured by Nihon Emulsion Co., Ltd. 100 series, Emalex 600 series, etc. Decaglycerin monofatty acid ester NIKKOL Decagln series manufactured by Nikko Chemicals, Ryoto (registered trademark) polyglycerester D series manufactured by Mitsubishi Chemical Foods, etc.

When the nonionic surfactant (E) is blended, it is preferable to add 0.3 to 2%, particularly 0.5 to 1% of the whole composition. If it is less than 0.3%, the appearance stability (no orientation) may not be improved. If it exceeds 2%, the adhesion of dental plaque to the tooth surface and the ability to sterilize mutans bacteria in the plaque will be satisfactorily exhibited. May not be. Further, the feeling of use may be reduced.

The liquid oral composition of the present invention can be prepared and applied as a mouthwash, a mouth freshener, a liquid dentifrice used by brushing with a toothbrush, a dentifrice gel, etc. Suitable as an agent.
According to the dosage form and the like of the present invention, an appropriate known arbitrary component can be blended in addition to the above components within a range not impairing the effects of the present invention. For example, wetting agents, thickeners, preservatives, sweeteners, fragrances other than component (C), surfactants other than component (E), active ingredients other than components (A) and (B), colorants, pH A regulator or the like can be added. In addition, it is not necessary to mix | blend an abrasive | polishing agent.

What is necessary is just to mix | blend the polyhydric alcohol of the said (D) component as a wetting agent.
Examples of the thickener include xanthan gum, sodium alginate, polyvinyl alcohol, hydroxyethyl cellulose, carrageenan, carboxymethyl cellulose sodium, polyvinyl pyrrolidone and the like. The blending amount of these thickeners is usually 0 to 3% of the whole composition.

Examples of the preservative include parabens such as sodium benzoate, methyl paraben, ethyl paraben, propyl paraben, and butyl paraben, cetylpyridinium chloride, alkyldiaminoethylglycine hydrochloride, potassium sorbate, and the like.
Examples of the sweetening agent include saccharin, saccharin sodium, steviosite, sucralose, reduced palatinose, erythritol, aspartame and the like.

Perfumes other than anethole, 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 Natural essential oils such as paracres oil, and l-menthol, l-carvone, cinnamic aldehyde, orange oil, 1,8-cineole, methyl salicylate, eugenol, thymol, linalool, limonene, menthone, menthyl acetate, citral, camphor, Perfume ingredients contained in the above natural essential oils such as borneol, pinene, spiranthol, etc., as well as ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl Nilglycidate, benzaldehyde, vanillin, ethyl vanillin, furaneol, maltol, ethyl maltol, gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, ethylene glycol Perfume ingredients such as l-menthyl carbonate, as well as some perfume ingredients and natural essential oils, apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee 1 type or 2 types or more of compounding flavors, such as brandy and yogurt. These fragrances can be used in the range of 0.00001 to 3% in the composition without impairing the effects of the present invention.

As the surfactant, anionic surfactants, amphoteric surfactants, cationic surfactants can be blended, such as alkyl sulfates such as sodium lauryl sulfate, lauroylmethyl taurine, acylamino acid salts, sodium dodecylbenzenesulfonate, Anionic surfactants such as α-sulfo fatty acid alkyl ester sodium and alkyl phosphate ester salts, betaine acetate type amphoteric surfactants such as alkyldimethylaminoacetic acid betaine and fatty acid amidopropyldimethylaminoacetic acid betaine, N-fatty acid acyl- Examples include imidazoline type amphoteric surfactants such as N-carboxymethyl-N-hydroxyethylethylenediamine salt, and amino acid type surfactants such as N-fatty acid acyl-L-alginate salts. The blending amount is usually 0 to 5%, particularly preferably 0.2 to 2%.

Examples of the active ingredient include bactericides such as chlorhexidine hydrochloride and alkyldiaminoethylglycine hydrochloride, anti-inflammatory agents such as tranexamic acid, epsilon-aminocaproic acid, allantoin, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, dextranase, amylase, Enzymes such as protease, mutanase, lysozyme, lytic enzyme, lytechenzyme, fluoride such as sodium fluoride, sodium monofluorophosphate, stannous fluoride, vitamin C such as azulene, lysozyme chloride, ascorbic acid, dihydrocholesterol , Glycyrrhetin salts, Glycyrrhetinic acids, Hydrocholesterol, Chlorophyll, Copper chlorophyllin sodium, Thyme, Ogon, Clove, Hamamelis It can be added copper gluconate, Karopeputaido, sodium polyphosphate, water-soluble inorganic phosphoric acid compounds, polyvinylpyrrolidone, anti-tartar agents, anti-plaque agents, potassium nitrate, aluminum lactate and the like. In addition, the compounding quantity of these other active ingredients can be made into an effective quantity in 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 can be added.
Examples of pH adjusters include phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid, carbonic acid and their potassium salts, sodium salts or ammonium salts, ribonucleic acid and salts thereof, sodium hydroxide, etc. 1 type or 2 or more types can be used, and what combined phosphoric acid and a citric acid, and those sodium salts is especially preferable. In this case, the liquid oral composition of the present invention preferably adjusts the pH at 25 ° C. to 5.5 to 8.5, and sodium dihydrogen phosphate and sodium monohydrogen phosphate as pH adjusters in the vicinity thereof. Alternatively, a combination of citric acid and sodium citrate can be used.

In addition, although purified water is mix | blended as a solvent, the compounding quantity can be 60% or more, especially 70% or more.

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.

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

[Examples and Comparative Examples]
Liquid oral compositions having the compositions shown in Tables 1 to 4 were prepared by a conventional method and evaluated as follows. The results are shown in Tables 1 to 4.

(I) Plaque adhesion inhibitory effect Pentax hydroxyapatite plate (radius 0.35 cm × height 0.35 cm or less, HAP plate) 3) Soaked 3 sheets for 30 seconds.
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 suppression effect:
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.

(II) Mutant bacteria bactericidal power in dental plaque Evaluation method of mutans bacteria bactericidal power 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, ultrasonic disruption (200 μA output for 10 seconds) and serial dilution (10-fold dilution for 6 stages) were performed, and 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 Hewit Broth (Becton and Dickinso
n company): 30g / L
Hemin (Sigma Aldrich): 5mg / L
Vitamin K (manufactured by Wako Pure Chemical Industries): 1mg / L
Purified water: Residue (Measured up so that the total amount becomes 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: Residue (Measured up so that the total amount becomes 1 L.)

* 5: Composition in 1 liter of Mitis-Salivarius agar plate medium supplemented with bacitracin Mitis-Salivarius Agar
(Becton and Dickinson): 90 g / 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.)

(III) Appearance stability (no tilt)
Appearance stability evaluation method:
The sample (liquid oral composition) is filled into a colorless and transparent PET container (manufactured by Yoshino Kogyo Co., Ltd.) having a filled volume of 500 mL, and stored in a 50 ° 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: No orientation is observed even when shaken.
○: Although very small orientation is observed when shaken, it is at a level with no problem.
Δ: Slight orientation is observed.
X: Considerable orientation is recognized.

(IV) Feeling of use (no astringency, bitterness or taste)
About 10 mL of sample (composition for liquid oral cavity) was included in the mouth, rinsed for 30 seconds, and the feeling after use for mouthwash was evaluated in the following four stages. The average score of 10 persons was evaluated according to the following criteria. , Δ, ×.
Usability evaluation criteria:
4 points: No astringency, bitterness or off-flavor.
3 points: Almost no astringency, bitterness or off-taste.
2 points: Slightly astringent, bitter, and off-flavor, slightly difficult to use.
1 point: There was considerable astringency, bitterness, and off-taste, and there was a hindrance to use.
Criteria for use feeling:
◎: 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

The main raw materials used in each example are as follows. The perfume composition A is as shown in Tables 5 to 11.
Cetylpyridinium chloride (manufactured by Wako Pure Chemical Industries, Ltd.)
Benzethonium chloride (Highamine 1622: Lonza Japan)
Hydroxyethylcellulose dimethyldiallylammonium chloride (trade name Cellcoat L-200: manufactured by Akzo Nobel)
(Product name Cell Coat H-100: manufactured by Akzo Nobel)
Leogard KGP (O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethylcellulose chloride: manufactured by Lion Corporation)
Anethole (manufactured by Wako Pure Chemical Industries)
Polyoxyethylene (100) hydrogenated castor oil (Nikko Chemicals)
Polyoxyethylene (60) hydrogenated castor oil (Nikko Chemicals)
Propylene glycol (Asahi Glass Co., Ltd.)
Glycerin (85%, Sakamoto Pharmaceutical Co., Ltd.)
Xylitol (Rocket Fleure)
Polyoxyethylene (20) cetyl ether (trade name EMALEX 120, manufactured by Nippon Emulsion Co., Ltd.)
Citric acid (manufactured by Fuso Chemical)
Sodium citrate (manufactured by Fuso Chemical)
Saccharin sodium (Daito Chemical Co., Ltd.)
Polyethylene glycol 400 (manufactured by NOF Corporation)

From the results of Tables 1 to 4, when (A) cationic fungicide or (B) hydroxyethylcellulose dimethyl diallylammonium chloride is not blended (Comparative Examples 1, 2, and 6), the appearance does not occur over time and the appearance is stable. However, it did not satisfy both the effects of suppressing the adhesion of plaque and the bactericidal effect of mutans bacteria in the plaque. Further, in the case of a composition in which the components (A) and (B) are blended, (C) anethole, or (D) a polyhydric alcohol and (E) a nonionic surfactant are lacking (Comparative Examples 3 and 5), C) When the ratio of anethole to the components (A) and (B) is inadequate (Comparative Example 4), neither occurrence of orientation can be suppressed and appearance stability is inferior. Even if a known fragrance was blended, the orientation could not be suppressed. On the other hand, the composition of the present invention (Example) is excellent in plaque adhesion inhibiting effect and sterilizing effect of mutans bacteria in plaque, and has a good appearance with almost no orientation even when stored at 50 ° C. for 1 month. It turned out that it became stable, and also there was no astringency, bitterness, and unpleasant taste, and the feeling of use was also good.

Note: In the table, parts are parts by mass (the same applies hereinafter).

Next, liquid oral compositions of the following formulation examples were similarly prepared and evaluated. These compositions were excellent in plaque adhesion inhibitory effect, sterilizing ability of mutans bacteria in plaque, appearance stability and feeling of use.

[Prescription Example 1]
Cetylpyridinium chloride 0.05%
Benzethonium chloride 0.01
Hydroxyethylcellulose dimethyl diallylammonium chloride (Cellcoat L-200) 0.01
Anethole 0.05
Polyoxyethylene hydrogenated castor oil (100) 0.5
Propylene glycol 3
Glycerin 4.5
Xylitol 3
Citric acid 0.03
Sodium citrate 0.25
Saccharin sodium 0.004
Purified water balance
Total 100.0%
(C) component / [(A) component + (B) component] = 0.71

[Prescription Example 2]
Benzethonium chloride 0.01%
Hydroxyethylcellulose dimethyl diallylammonium chloride (Cellcoat L-200) 0.01
Anethole 0.05
Polyoxyethylene hydrogenated castor oil (100) 0.5
Propylene glycol 3
Glycerin 4.5
Xylitol 3
Citric acid 0.03
Sodium citrate 0.25
Saccharin sodium 0.004
Purified water balance
Total 100.0%
(C) component / [(A) component + (B) component] = 2.5

[Prescription Example 3]
Cetylpyridinium chloride 0.05%
Hydroxyethylcellulose dimethyl diallylammonium chloride (Cellcoat L-200) 0.01
Anethole 0.05
Polyoxyethylene hydrogenated castor oil (80) 0.5
Propylene glycol 3
Glycerin 4.5
Xylitol 3
Citric acid 0.03
Sodium citrate 0.25
Saccharin sodium 0.004
Purified water balance
Total 100.0%
(C) component / [(A) component + (B) component] = 0.83

[Prescription Example 4]
Cetylpyridinium chloride 0.05%
Hydroxyethylcellulose dimethyl diallylammonium chloride (Cellcoat L-200) 0.01
Anethole 0.05
Polyoxyethylene hydrogenated castor oil (100) 0.5
Propylene glycol 3
Glycerin 4.5
Polyethylene glycol 400 4
Citric acid 0.03
Sodium citrate 0.25
Saccharin sodium 0.004
Purified water balance
Total 100.0%
(C) component / [(A) component + (B) component] = 0.83

Claims

A liquid oral composition substantially free of ethanol is blended with (A) a cationic fungicide and (B) hydroxyethyl cellulose dimethyl diallylammonium chloride, and (C) anethole is added to component (C) / [(A). Component + (B) component] is used in a mass ratio of 0.1 to 10, and (D) a polyhydric alcohol and / or (E) a nonionic surfactant is blended. Liquid oral composition.
(A) The composition for liquid oral cavity according to claim 1, wherein the cationic fungicide is cetylpyridinium chloride.
The liquid oral composition according to claim 1 or 2, wherein 0.01 to 0.1% by mass of component (A) is blended.
The liquid oral composition according to claim 1, 2 or 3, wherein 0.01 to 0.2% by mass of component (C) is blended.
The liquid oral composition according to any one of claims 1 to 4, wherein the amount of ethanol in the composition is 100 ppm or less.
A liquid oral composition substantially free of ethanol is blended with (A) a cationic fungicide and (B) hydroxyethyl cellulose dimethyl diallylammonium chloride, and (C) anethole is added to component (C) / [(A). Component + (B) component] is used in a range of 0.1 to 10 as a mass ratio, and (D) a polyhydric alcohol and / or (E) a nonionic surfactant is blended, A method of stabilizing and blending the components (A) and (B) in the composition.
The method according to claim 6, wherein the amount of ethanol in the composition is 100 ppm or less.