KR101936969B1 - Liquid composition for oral cavity and method for stable addition of components to composition - Google Patents

Abstract

Provided is a liquid oral composition which does not contain ethanol, which is excellent in the adhesion inhibition effect of plaques and the microbicidal disinfecting power in plaques, but also has excellent appearance stability and good palatability. (A) a cationic fungicide and (B) hydroxyethyl cellulose dimethyldiallylammonium chloride, (C) adding anethole to the liquid oral composition substantially free of ethanol as component (C) (D) a polyhydric alcohol and / or (E) a non-ionic surfactant in combination in a ratio of [Component (A) + Component (B)] in the range of 0.1 to 10 in mass ratio. Composition. (A) and (B) are added to the liquid oral composition and the component (C) is used in combination in a range of from 0.1 to 10 (C) / [(A) + (B) (D) and / or (E), and stabilizing the components (A) and (B) in the composition.

Description

TECHNICAL FIELD [0001] The present invention relates to a liquid oral composition and a method for stabilizing a composition in the composition.

An object of the present invention is to provide a pharmaceutical composition which is excellent in palatability to plaque and has excellent microbial sterilizing power in plaque and excellent appearance stability (no sediment) and excellent palatability, Liquid oral composition and a method of stabilizing and compounding the composition in the composition.

In order to prevent periodontal diseases and ingestion, suppression of plaque is important, and oral compositions containing a bactericide for plaque inhibition are widely used. Of these fungicides, cationic fungicides are widely used because they have a sterilizing effect of oral bacteria, an effect of suppressing plaque, and an effect of improving dental floss. Further, hydroxyethyl cellulose dimethyldiallylammonium chloride has a property of being easily adsorbed on the surface of teeth, and a liquid oral composition capable of effectively suppressing formation of plaque by using the composition is disclosed in Patent Document 1 (Japanese Patent Laid- 64137). In addition, it is known that the adhesion inhibition effect of plaque is synergistically improved by combining a cationic polymer with cetylpyridinium chloride (CPC), which is a cationic fungicide, and the like (Patent Document 2: Japanese Patent Application Laid-Open No. 2000-34213). In addition, a combination of hydroxyethyl cellulose dimethyldiallylammonium chloride and a cationic fungicide is known and various related arts have been proposed (Japanese Patent Application Laid-Open No. 2001-139442, Patent Document 4, Japanese Patent Laid- 2001-139443).

All of the foregoing prior arts allow the blending of ethanol. In recent years, there has been a problem in that irritation due to alcohol has occurred in a feeling of feeling of low stimulation, and the composition of the non-alcohol tends to be desired.

However, in the case where ethanol is not blended, it is difficult to secure the appearance stability in the composition comprising the cationic fungicide and hydroxyethyl cellulose dimethyldiallylammonium chloride, and it is difficult to secure both the irritation and the stability of the appearance over time there is a problem. In addition, there is a case where a bitter taste, a bitter taste, or an unpleasant taste derived from a cationic bactericide and hydroxyethyl cellulose dimethyldiallylammonium chloride occurs, and the effect of both components and the palatability of the preparation Sex).

Patent Document 1: JP-A-2001-64137 Patent Document 2: Japanese Patent Application Laid-Open No. 2000-34213 Patent Document 3: Japanese Patent Application Laid-Open No. 2001-139442 Patent Document 4: Japanese Patent Application Laid-Open No. 2001-139443

Therefore, a technique capable of stably mixing a cationic fungicide and hydroxyethyl cellulose dimethyldiallylammonium chloride in a liquid preparation containing no ethanol to ensure appearance stability, and to make both the effects of both components and palatability of the preparation both compatible Is desired. Disclosure of the Invention The present invention has been made in view of the above circumstances, and it is an object of the present invention to provide a composition for liquid oral cavity which is substantially free of ethanol and which is excellent in appearance stability and excellent in palatability, And to provide a method of stabilizing the components in the composition.

The inventors of the present invention have conducted intensive studies in order to achieve the above object, and as a result, the inventors of the present invention found that (A) a cationic bactericide and (B) hydroxyethyl cellulose dimethyldiallylammonium chloride were mixed in a liquid oral composition substantially free of ethanol (D) a polyhydric alcohol and / or (E) an anthole in an amount of 0.1 to 10 in terms of the mass ratio of the component (C) / [component (A) + component (B) By combining the nonionic surfactant, it is possible to improve the stability of the external appearance over time by suppressing the occurrence of sedimentation while being excellent in the adhesion inhibiting effect of plaques and the microbicidal disinfecting power in plaques, The inventors of the present invention have accomplished the present invention.

The present applicant has found that a liquid oral composition comprising a cationic fungicide and cationic cellulose and a propylene glycol, polyoxyethylene hydrogenated castor oil, and p-oxybenzoic acid ester in a liquid oral composition substantially free of ethanol Japanese Patent Application No. 2010-280009 (Japanese Patent Laid-Open Publication No. 2011-148770) proposes an antifouling coating composition which is excellent in antifouling effect of plaques and antimicrobial activity of microspheres in plaques and excellent in antifouling strength and appearance stability. This liquid oral composition is excellent in appearance stability (no sediment) after storage at 5 占 폚 for one month. On the other hand, the inventors of the present invention have found that, in the liquid oral composition containing no ethanol, when the cationic bactericide is mixed with the cationic cellulose, it is difficult to stably maintain the outer appearance of the preparation, The inventors of the present invention have studied a technique for stabilizing the cationic fungicide and the cationic cellulose by knowing that the preservation results in sedimentation and deterioration in appearance stability. As a result, it has been found that anethole is effective as a stabilizer even when unexpectedly, and when a composition for oral cavity containing no ethanol is mixed with a cationic bactericide and hydroxyethyl cellulose dimethyldiallylammonium chloride in combination, And therefore contributes to improvement in appearance stability. Therefore, by appropriately blending anethole in the composition in which both components are used in combination, and by blending a polyhydric alcohol and / or a nonionic surfactant, high appearance stability And excellent effects of the two components can be suppressed and the palatability, bitter taste, odd taste, etc. derived from these components can be suppressed and good palatability can be maintained and exerted.

It is known that anethole is used as an antioxidant in oral compositions, but is effective for stabilizing formulation of a cationic bactericide and hydroxyethyl cellulose dimethyldiallylammonium chloride in a liquid oral composition not containing ethanol, It is possible to obtain a high appearance stability with little sedimentation even if it is stored for one month at a temperature of 100.degree. C. for 1 month, and it is a new knowledge of the present inventor that a liquid preparation achieving the above-mentioned remarkable effect can be obtained.

Accordingly, the present invention provides a composition for liquid oral cavity as described below and a method for stabilizing components in the composition.

[I]

(A) a cationic fungicide and (B) hydroxyethyl cellulose dimethyldiallylammonium chloride, (C) adding anethole to the liquid oral composition substantially free of ethanol as component (C) (D) a polyhydric alcohol and / or (E) a non-ionic surfactant in combination in a ratio of [Component (A) + Component (B)] in the range of 0.1 to 10 in mass ratio. Composition.

[II]

(A) a cationic fungicide and (B) hydroxyethyl cellulose dimethyldiallylammonium chloride, (C) adding anethole to the liquid oral composition substantially free of ethanol as component (C) (D) a polyhydric alcohol and / or (E) a nonionic surfactant in the range of 0.1 to 10 in terms of a mass ratio of the component (A) and the component (B) (A) and (B).

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a liquid oral composition substantially free of ethanol, which is excellent in appearance stability and palatability, while being excellent in the effect of suppressing adhesion of plaques and the microbicidal disinfecting power in plaques.

Hereinafter, the present invention will be described in more detail. The liquid oral composition of the present invention is characterized by comprising (A) a cationic bactericide, (B) hydroxyethyl cellulose dimethyldiallylammonium chloride, (C) anethole, (D) a polyhydric alcohol and / or (E) It contains an active agent.

The cationic bactericide as the component (A) is an effective ingredient for inhibiting adhesion of the plaque to the tooth surface and sterilizing the mutant bacteria in the plaque. Specific examples thereof include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride and the like, and one kind or a mixture of two or more kinds of them can be used. Among them, cetylpyridinium chloride is preferable in terms of sterilizing power, handling property and usability.

The amount of the cationic fungicide as the component (A) is preferably from 0.01 to 0.1% (mass% or less), more preferably from 0.02 to 0.05%, of the whole composition from the viewpoints of suppression of plaque adhesion to the tooth surface and microbial sterilizing power in the plaque Do. If it is less than 0.01%, the effect of suppressing the attachment of the plaque to the tooth surface and the microbicidal activity of the microorganisms in the plaque may not be satisfactorily exhibited. If it is more than 0.1%, a bitter, bitter or strange taste originating from a cationic fungicide may be produced.

(B) Hydroxyethyl cellulose Dimethyldiallylammonium chloride is a cationic polymer, and is compounded as an active ingredient for inhibiting the attachment of a plaque to a tooth surface. By combining the component (B) together with the cationic fungicide, which is the component (A), the effect of inhibiting adhesion of the plaque on the tooth surface can be improved, the mutant bacteria in the plaque can be effectively sterilized, High plaque formation inhibiting effect is achieved.

As the hydroxyethyl cellulose dimethyldiallylammonium chloride, a commercially available product can be used, and for example, the following can be exemplified.

Cellcoat L-200 (manufactured by Akzo Nobel Co., Ltd.):

A nitrogen content of 0.1 to 3% and a viscosity of 2% aqueous solution of 30 to 3,000 mPa 占 퐏 (BH type

Brock Field Viscometer, Rotor No. 2, 20 revolutions, 21 캜, measuring time 1 min)

Cellcoat H-100 (manufactured by Akzo Nobel Co., Ltd.):

A nitrogen content of 1.0% and a viscosity of 2% aqueous solution of 500 to 2,750 mPa · s (BH type Brookfield viscometer, rotor No. 2, 20 revolutions, 21 캜, measuring time of 1 minute)

The blending amount of hydroxyethyl cellulose dimethyldiallylammonium chloride as the component (B) is preferably 0.005 to 0.5%, particularly 0.01 to 0.05% of the whole composition. When the content is less than 0.005%, the effect of suppressing the attachment of the plaque may not be satisfied satisfactorily. If it is more than 0.5%, sedimentation may occur to deteriorate the appearance stability (no sediment), or a pungent taste, a bitter taste, or an unusual taste derived therefrom may occur, and the feeling of use may be lowered.

Anethole, component (C), is incorporated as a stabilizer. By mixing anethole, it is possible to improve the appearance stability by suppressing sediment with time, and also to improve the usability feeling (bitter taste, bitter taste, no strange taste).

The blending amount of (C) anethole is preferably 0.01 to 0.2%, particularly 0.01 to 0.1%, based on the whole composition. If the blending amount is less than 0.01%, the appearance stability (no sediment) can not be satisfactorily improved. In addition, there is a case that the feeling of use (no bitter taste, bitter taste, or unusual taste) can not be improved. If it exceeds 0.2%, the appearance stability (no sediment) may be impaired and the feeling of use (odd taste) may be lowered.

In the present invention, the mass ratio of the component (C) / [component (A) + component (B)] is 0.1 to 10, preferably 0.2 to 2. By combining the components (A) and (B) in the above-described proportions, the appearance stability of the preparation can be improved by suppressing the occurrence of sedimentation due to the combination of components (A) and (B) The feeling of use can be improved. When the content is less than 0.1, a pungent taste, a bitter taste, an odd taste and the like are produced, the palatability is kept good and the sediment can not be suppressed, and if it exceeds 10, the appearance stability (no sediment) is damaged.

In the present invention, by blending (D) a polyhydric alcohol and / or (E) a nonionic surfactant together with (C) anethole, the components (A) and (B) can be stabilized and the appearance stability have. Any of the components (D) and (E) may be blended, or the components (D) and (E) may be used in combination in view of effect.

Examples of the polyhydric alcohol (D) include polyethylene glycol such as propylene glycol, glycerin, xylitol, sorbitol ethylene glycol and polyethylene glycol, polypropylene glycol, maltitol, and lactate. These may be used alone or in combination of two or more.

When the polyhydric alcohol as the component (D) is blended, it is preferable to add 2 to 20%, particularly 2 to 15%, of the whole composition. If it is less than 2%, the appearance stability (no sediment) can not be satisfactorily improved. If it exceeds 20%, a strange taste derived from a polyhydric alcohol may be produced, and a feeling of use (bitter taste, bitter taste, no abnormal taste) may be damaged.

As the nonionic surfactant (E), those conventionally used in oral compositions can be used, and polyoxyethylene hardened castor oil, polyoxyethylene alkyl ether, decaglycerol mono fatty acid ester and the like can be suitably used. (Cetyl) to 18 (stearyl) of the alkyl group and an average addition mole number of the ethylene oxide is 20 to 40 moles, the polyether polyol having an average addition mole number of ethylene oxide of 60 to 100 moles, Oxyethylene alkyl ethers, decaglycerol mono fatty acid esters of fatty acids having carbon numbers of 12 (lauric acid) to 18 (stearic acid), particularly 12 to 14 (myristic acid), and the like, . Among them, a polyoxyethylene hydrogenated castor oil is preferable from the viewpoints of exhibiting the ability to suppress the attachment of the plage to the tooth surface, the ability to sterilize the muscarinic bacteria in the plaque, and the appearance stability (no sediment) Is preferably 60 to 100 moles. When the average addition mole number of ethylene oxide is less than 60 moles, there is a case in which sedimentation occurs at the product stored at 50 ° C, and appearance stability (no sedimentation) is impaired, and those having a molecular weight exceeding 100 moles are not generally commercially available.

Specifically, the following commercially available products can be used.

· Polyoxyethylene hydrogenated castor oil

NIKKOL HCO system of Nikko Chemical Injection, Emarex HC system of Nihon Emulsion Co., Ltd., Uniox HC system of Nichiyusha Co., Ltd.

Polyoxyethylene alkyl ether

Emarex 100 series manufactured by Nihon Emulsion Co., Ltd., Emarex 600 series, etc.

· Decaglycerol mono fatty acid ester

NIKKOL Decagln series manufactured by Nikko Chemical Co., Ltd., and Pori Griester D series manufactured by Mitsubishi Chemical Foods Co., Ltd.

When the nonionic surfactant as the component (E) is incorporated, 0.3 to 2%, particularly 0.5 to 1%, of the total composition is preferably added. If the content is less than 0.3%, the appearance stability (no sedimentation) can not be improved. If the content is more than 2%, the detachment of the plaque on the tooth surface and the microbicidal disinfecting power in the plaque may not be satisfied satisfactorily. Also, the feeling of use may be lowered.

The liquid oral composition of the present invention can be prepared and applied as a curing agent, a mouth refreshing agent, a liquid skimming agent and a skim gel used by brushing with a toothbrush, and is particularly suitable as a curing agent or a liquid skimming agent .

In the composition of the present invention, in addition to the above-mentioned components, any well-known optional ingredients may be incorporated in accordance with the form of the composition and the like within a range not to impair the effect of the present invention. For example, a wetting agent, a thickener, a preservative, a sweetener, a colorant other than the component (C), a surfactant other than the component (E), an effective component other than the components (A) and (B) . The abrasive may not be blended.

As the wetting agent, a polyhydric alcohol as component (D) may be added.

Examples of the thickening agent include xanthan gum, sodium alginate, polyvinyl alcohol, hydroxyethylcellulose, carrageenan, carboxymethylcellulose sodium, polyvinylpyrrolidone, 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, methylparaben, ethylparaben, propylparaben and butylparaben, cetylpyridinium chloride, alkyldiaminoethylglycine hydrochloride, and potassium sorbate.

Examples of the sweetening agent include saccharin, sodium saccharin, tebioside, sucralose, reduced palatinose, erythritol, aspartame, and the like.

Examples of the flavoring agent include those other than anethole such as peppermint oil, spearmint oil, eucalyptus oil, wintergreen oil, clove oil, time oil, sage oil, cardamon oil, rosemary oil, marjoram oil, lemon oil, Natural essential oils such as vegetable oils and paracrine oils and natural essential oils such as l-menthol, l-carboen, cinnamic aldehydo, orange oil, 1,8-cineol, methyl salicylate, A minor component such as ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl (meth) acrylate, isophorone diisocyanate and the like, which are contained in the natural essential oils such as limonene, menton, mentyl acetate, citral, camphor, borneol, pinene, But are not limited to, anthranilate, ethylmethylphenylglycidate, benzaldehyde, vanillin, ethyl vanillin, pran neol, maltol, ethyl maltol, gamma / delta decalactone, gamma / delta undecalactone, Amide, mesyllactate, ethylene glycol-1-menthylcarbo Fruit, such as apple, banana, strawberry, blueberry, melon, beach, pineapple, grape, muscat, wine, cherry, squash, coffee, brandy , Yogurt, and the like. These dyes may be used in the range of 0.00001 to 3% in the composition and not interfering with the effect of the present invention.

As the surfactant, anionic surfactants, amphoteric surfactants and cationic surfactants can be added. Examples thereof include alkylsulfates such as sodium laurylsulfate, lauroylmethyltaurine, acylamino acid salts, sodium dodecylbenzenesulfonate, anionic surfactants such as alkyl sulfates of? -sulfo fatty acids, sodium salts and alkylphosphoric acid ester salts; amino acid betaine type amphoteric surfactants such as alkyldimethylaminoacetic acid betaine and fatty acid amidepropyldimethylaminoamino acid betaine; An imidazoline-type amphoteric surfactant such as carboxymethyl-N-hydroxyethylethylenediamine salt, and an amino acid-type surfactant such as N-fatty acid acyl-L-alginate salt. The blending amount is usually 0 to 5%, particularly preferably 0.2 to 2%.

Examples of effective components include antimicrobial agents such as chlorhexidine hydrochloride and alkyldiaminoethylglycine hydrochloride, antineoplastic agents such as tranexamic acid, epsilon aminocaproic acid, allantoin, allantoin hydrochloride aluminum and allantoin dihydroxy aluminum , Enzymes such as dextranase, amylase, protease, mutagen, lysozyme, lytic enzyme, reticence enzyme, sodium fluoride, sodium monofluorophosphate, fluoride such as 1 tin fluoride, azulene, lysozyme chloride, ascorbic acid Plant extracts such as vitamin C, dihydrocholesterol, glycyrrhetinic acid, glycyrrhetinic acid, hydrocholesterol, chlorophyll, copper chlorophyllin sodium, thyme, gold, sperm, and hammamelis, copper gluconate, Tid, sodium polyphosphate, water-soluble inorganic phosphate compound, polyvinylpyrrolidone, anti-calculus agent, anti-plaque agent, potassium nitrate, It can be added. The blending amount of these other active ingredients may be an effective amount within a range not hindering the effect of the present invention.

As a coloring agent, a water-soluble coloring matter having a high safety such as Blue No. 1, Green No. 3, Yellow No. 4 or Red No. 105 may be added.

As the pH adjusting agent, one or two or more of phthalic acid, phosphoric acid, citric acid, succinic acid, acetic acid, fumaric acid, malic acid, carbonic acid or their potassium salt, sodium salt or ammonium salt, ribonucleic acid or its salt, sodium hydroxide, Particularly, a combination of phosphoric acid, citric acid and their sodium salt is preferable. In this case, it is preferable that the liquid oral composition of the present invention is adjusted to pH 5.5 to 8.5 at 25 ° C, and sodium dihydrogenphosphate and sodium dihydrogenphosphate, or citric acid and sodium citrate Can be used.

In addition, purified water is added as a solvent, but the blending amount thereof can be 60% or more, particularly 70% or more.

The liquid oral composition of the present invention is substantially free of ethanol. Here, the expression " 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, and the lower limit is 0 ppm . In addition, the liquid oral composition of the present invention is ethanol-free but may contain a trace amount of ethanol derived from the raw material in the antioxidant compounded in the composition. Therefore, considering these reasons, It does not contain ethanol in addition to ethanol.

Example

Hereinafter, examples, comparative examples and formulations are shown and the present invention will be described in detail, but the present invention is not limited to the following examples. In the following examples,% represents mass% unless otherwise specified.

[Practical example, comparative example]

Liquid oral compositions having the compositions shown in Tables 1 to 4 were prepared by a routine method, and the following evaluations were carried out. The results are shown in Tables 1-4.

(I) Effect of preventing plaque adhesion

2 ml each of the liquid oral composition was put in a 24-well multiplate, and three mirror-polished hydroxyapatite plates (radius 0.35 cm x height 0.35 cm or less, HAP plate) made by Pentax Inc. were immersed for 30 seconds.

Into a 24-well multiplate, 2 mL of Streptococcus mutans 10449 strain buffer ^{1 * in} which turbidity at a wavelength of 660 nm was dispersed to a degree of 0.35 was added, and the HAP plates were immersed in triplicate to obtain 37 Lt; 0 > C for 2 hours to adhere bacteria. Next, the HAP plate was taken out and washed with sterilized water, and the HAP plates washed in ² ml of a liquid medium (culture medium) ^{* 2} were immersed in three sheets at 37 占 폚 for 8 hours, and the adherent bacteria were cultured. Washed with distilled water, dyed with a flage dyeing solution, measured for a value in a colorimeter, and the average value of the three sheets was calculated. The evaluation criteria are as follows.

Evaluation criteria of plaque adhesion inhibition effect:

?: Average value of a is less than 5

○: Average value of a is 5 or more and less than 7.5

?: Average value of a is 7.5 or more and less than 10

X: average value of a value of 10 or more

* 1: Composition of buffer

Dissolving the potassium chloride (KCl) 3.37g, potassium dihydrogenphosphate (KH ₂ PO ₄₎ 0.14g, calcium chloride (CaCl ₂₎ 0.11g, magnesium chloride (MgCl ₂₎ 0 .02g the 800㎖ purified water, potassium hydroxide (KOH) To adjust the pH to 7.0, and to make up the total volume to 1 L with purified water.

* 2: Composition of liquid medium

 3 g of tryptic soy broth, and 0.5 g of sucrose were dissolved in 100 ml of purified water.

(II) Sterilization of mutans bacteria in plaque

Evaluation method of mutant bactericidal activity in plaque:

Actinomyces naeslundii T14V strain, Fusobacterium nucleatum ATCC 10953 strain, Lepidonia spp., Which has been stored (cryopreserved) in the Oral Care Research Center, (Sigma Aldrich), which was autoclaved at 121 ° C for 15 minutes, and 40 μl of each strain of Streptococcus mutans ATCC 25175 strain of Porphyromonas gingivalis W50 strain, Streptococcus mutans ATCC 25175, and 1 mg / Was added to 4 ml of Todd-Hewitt-broth (manufactured by Becton and Dickinson) (THBHM ^{* 3} ) containing K (manufactured by Wako Pure Chemical Industries, Ltd.) and incubated overnight at 37 ° C (80 vol.% Nitrogen, 10 vol. 10 vol% hydrogen). After the cultivation, 300 μl of each of the mycorrhizal fluids (4 kinds) was collected, added to 30 ml of THBHM, and further cultured overnight. After cultivation, the supernatant was discarded by centrifugation (10,000 rpm, 10 min) of each bacterial liquid. (BMM ^{* 4} ) autoclaved at 121 ° C for 15 minutes was added to each of the sediments (bacterium), and the cells were resuspended and cultured in a culture tank (diameter 140 mm × height 200 mm ) and in the respective bacterial counts each 1 × 10 ⁷ gae / ㎖ to the inoculation, and the stirrer (diameter × length 10㎜ 51㎜) and stirred (while rotating at about 100rpm), 37 ℃, anaerobic conditions using ( 95 vol% nitrogen, 5 vol% carbon dioxide dioxide) overnight. Thereafter, BMM was supplied at a rate of 100 ml / h, and the culture liquid was discharged at the same rate. The culture liquid discharged from the culture tank was continuously supplied to another culture tank (90 mm in diameter × 190 mm in height) in which the liquid amount was maintained at 300 ml.

A hydroxyapatite disk (7 mm in diameter x 3.5 mm in height) as an attachment carrier was mounted on the turntable (rotating at about 80 rpm) in the culture tank, and a plaque was artificially formed on the surface thereof.

Cultivation by the above method was carried out for 14 days, and the following treatments were carried out for the next 7 days. Namely, the hydroxyapatite disks attached with the plaques were taken out from the culture tank three times a day, and each was transferred to each chalet (25 mm in diameter × 14 mm in height), and 5 g of the test composition (Example and Comparative Example) Lt; / RTI > Thereafter, after washing three times with 5 g of physiological saline, it was returned to the culture tank again. This operation was performed seven times in total.

At the end of the culture, the plaque was transferred to a test tube (diameter 13 mm x 100 mm) to which 4 ml of physiological saline was added in order to evaluate the microbicidal disinfecting power in the plaque of the test composition. Each broth was applied onto the Mitis-Salivarius agar plate medium ^{* 5} with bacitracin prepared by the usual method, and the broth was applied (step Respectively. The plate medium was anaerobically cultured (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) until the colonies could be visually confirmed. After counting the number of colonies of each plate culture medium, viable cell counts were calculated. In addition, as a control, the same treatment was performed using purified water instead of the test composition to calculate the viable cell count in the plaque. The ratio of viable cell counts treated with each test composition when the viable cell count of the cells treated with purified water was regarded as 100% was measured and expressed by the following criteria.

Evaluation standard :

◎: Less than 1% of remaining viable cells

○: The number of remaining viable cells is 1% or more and less than 10%

△: Number of remaining viable cells 10% or more and less than 50%

X: The number of remaining viable cells was 50% or more

* 3: Composition of THBHM (expressed in mass per liter)

Todd-Hewitt-Broth (manufactured by Becton and Dickinson) 30 g / l

Hemin (manufactured by Sigma-Aldrich): 5 mg / l

Vitamin K (manufactured by Wako Pure Chemical Industries, Ltd.): 1 mg / l

Purified Water: Rest

(Mass-up to a total volume of 1 L)

* 4: Composition of BMM (expressed in mass per liter)

Proteose peptone (manufactured by Becton and Dickinson): 2 g / l

Tryptone (manufactured by Becton and Dickinson): 1 g / l

Moutin (manufactured by Sigma-Aldrich): 2.5 g / l

Hemin (manufactured by Sigma-Aldrich): 1 mg / l

Vitamin K (manufactured by Wako Pure Chemical Industries, Ltd.): 0.2 mg / l

KCl (manufactured by Wako Pure Chemical Industries, Ltd.): 0.5 g / l

Cysteine (manufactured by Wako Pure Chemical Industries, Ltd.): 0.1 g / l

Purified Water: Rest

(Mass-up to a total volume of 1 L)

* 5: Composition of 1 liter of Bacitracin-added Mitis-Salivarius agar plate medium

Mitis-Salivarius Agar (manufactured by Becton and Dickinson): 90 g / l

Bacitracin (manufactured by Sigma-Aldrich): 200 U / L

(Bacitracin was prepared by first preparing an aqueous solution having a concentration of 200,000 / L at 1,000-fold concentration, autoclaving MS agar, and adding 1/1000 of the medium at a temperature of about 50 DEG C after cooling)

(III) Appearance stability (no sediment)

Evaluation method of appearance stability:

450 mL of a colorless transparent PET container (Yoshino Kogyo Co., Ltd.) of 500 mL in a mortar was charged, and the appearance stability after storage for 1 month in a 50 ° C thermostatic chamber (MPO-311, manufactured by Sanyo Denki Co., Ltd.) , A visual judgment was made.

Evaluation criteria for appearance stability:

◎: No sediment is recognized even if shaking.

○: A very fine sediment is recognized at the time of shaking, but it is a problem-free level.

△: Slight sediment is recognized.

X: Considerable sediment is recognized.

(Ⅳ) Feeling of feeling (bitter taste, bitter taste, no strange taste)

About 10 ml of the sample (liquid oral composition) was put in the mouth and the mouth was soaked for 30 seconds, and the feeling after use was evaluated in the following four steps. The average of 10 persons was evaluated as?,?,? X.

Evaluation criteria of feeling:

4 points: There was no bitter taste, bitter taste, strange taste.

3 points: There was little bitter taste, bitter taste, strange taste.

2 points: There was a bitter taste, bitter taste, strange taste, and it was difficult to use a little.

1 point: It has a bitter taste, a bitter taste, a strange taste, and it has trouble to use.

Acceptance criteria:

◎: Average point 3.5 or more and 4.0 or less

○: 3.0 points or more and less than 3.5 points

△: Average point of 2.0 points or more and less than 3.0 points

X: Average point less than 2.0 point

The main raw materials in each example are as follows. Further, for the composition A of the present invention,

As shown.

Cetylpyridinium chloride (manufactured by Wako Pure Chemical Industries, Ltd.)

Benzenethonium chloride (Hiamine 1622: manufactured by Lonsa Japan)

Hydroxyethylcellulose dimethyldiallylammonium chloride

 (Trade name: Cellcoat L-200, manufactured by Akzo Nobel)

 (Trade name: Cellcoat H-100, manufactured by Akzo Nobel)

(Trade name, product of Lion Corporation) was added to the reaction mixture,

Anethole (manufactured by Wako Pure Chemical Industries, Ltd.)

Polyoxyethylene (100) hardened castor oil (Nikko Chemical Injection)

Polyoxyethylene (60) hardened castor oil (Nikko Chemical Injection)

Propylene glycol (manufactured by Asahi Glass Co., Ltd.)

Glycerin (85%, manufactured by Sakamoto Pharmaceutical Industry Co., Ltd.)

Xylitol (manufactured by Rocket Furure)

Polyoxyethylene (20) cetyl ether (trade name: Emarex 120, manufactured by Nihon Emulsion Co., Ltd.)

Citric acid (manufactured by Fuso Chemical)

Sodium citrate (manufactured by Fusoh Chemical)

Sodium saccharin (manufactured by Daito Chemicals)

Polyethylene glycol 400 (Nichiyusha Co.)

[Table 1]

[Table 2]

[Table 3]

[Table 4]

From the results of Tables 1 to 4, it can be seen that when no cationic bactericide (A) or hydroxyethyl cellulose dimethyldiallylammonium chloride (B) is blended (Comparative Examples 1, 2 and 6) The appearance stability was good, but the effect of the plaque adhesion inhibiting effect and the mutans bactericidal effect in the plaque was not satisfied. (C) Anethole or (D) polyhydric alcohol and (E) nonionic surfactant were not contained (Comparative Examples 3 and 5), (C) In the case where the ratio of anethole to the components (A) and (B) is inadequate (Comparative Example 4), all of the precipitates can not be suppressed and the appearance stability is poor. In Comparative Example 7, It was not possible to suppress sediment even if it was blended. In contrast, the composition (Example) of the present invention is excellent in the effect of suppressing the attachment of plaque and the microbicidal effect of bacteria in plaques, and exhibits little sedimentation and good appearance stability even after storage at 50 占 폚 for one month, , No bitter taste, no strange taste, and good feeling.

[Table 5]

[Table 6]

NOTE; In the table, a part is a mass part (hereinafter the same).

[Table 7]

[Table 8]

[Table 9]

[Table 10]

[Table 11]

Next, the liquid oral composition of the following formulation was similarly prepared and evaluated. These compositions were excellent in the effect of suppressing the attachment of plaque, the sterilizing power of the mutans bacteria in the plaque, the appearance stability and feeling of use.

[Prescription Example 1]

Cetylpyridinium chloride 0.05%

0.01 benzethonium chloride

Hydroxyethylcellulose dimethyldiallylammonium 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) / [(A) + (B)] = 0.71

[Prescription Example 2]

0.01% benzethonium chloride

Hydroxyethylcellulose dimethyldiallylammonium 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 dimethyldiallylammonium 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) / [(A) + (B)] = 0.83

[Prescription Example 4]

Cetylpyridinium chloride 0.05%

Hydroxyethylcellulose dimethyldiallylammonium 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) / [(A) + (B)] = 0.83

Claims (7)

In the liquid oral composition wherein the amount of ethanol in the composition is 100 ppm or less,
(A) 0.02 to 0.05 mass% of at least one cationic fungicide selected from cetylpyridinium chloride, benzethonium chloride and benzalkonium chloride, and
(B) hydroxyethyl cellulose dimethyldiallylammonium chloride in an amount of 0.01 to 0.05 mass%
(C) anethole in an amount of from 0.01 to 0.1% by mass, and the component (C) / (component (A) + component (B)
(D) 2 to 15% by mass of a polyhydric alcohol and / or (E) 0.5 to 1% by mass of a nonionic surfactant. The method according to claim 1,
(A) a liquid oral composition characterized in that the cationic bactericide is cetylpyridinium chloride. 3. The method according to claim 1 or 2,
Wherein the nonionic surfactant (E) is a polyoxyethylene hydrogenated castor oil. (A) 0.02 to 0.05 mass% of at least one cationic fungicide selected from cetylpyridinium chloride, benzethonium chloride and benzalkonium chloride, and (B) at least one compound selected from the group consisting of hydroxy (C) an anthole in an amount of 0.01 to 0.1 mass% and a component (C) / [component (A) + component (B)] in an amount of 0.01 to 0.05 mass% (D) 2 to 15% by mass of a polyhydric alcohol and / or (E) 0.5 to 1% by mass of a nonionic surfactant are blended in the range of 0.2 to 2,
Wherein the components (A) and (B) are stabilized and formulated in the liquid oral composition. delete delete delete