JP6471667B2 - Liquid oral composition - Google Patents

Description

  The present invention relates to a liquid oral composition that has both an excellent remineralization promoting effect and a continuous bactericidal effect against caries-causing bacteria, and is effective in preventing or suppressing caries.

  When tooth enamel and dentin are exposed to acids produced by oral bacteria, they lose their mineral components and caries develops and progresses. However, if there is no clear defect in the caries surface layer and only the mineral ions inside the caries are eluted, the mineral ions are supplied to the inside of the initial caries by appropriate oral care and remineralized. It is known to improve to the original state.

Examples of methods for preventing caries include promotion of remineralization of the tooth surface and sterilization of caries-causing bacteria. Recalcification can be promoted by supplying calcium ions and phosphate ions to the teeth, and the presence of fluoride ions forms fluoroapatite that is difficult to decalcify by acid, thereby restoring initial caries. And it is known that it has the effect of promoting remineralization.
Furthermore, in order to enhance the caries prevention effect, it is effective to continuously provide a high bactericidal effect against caries-causing bacteria with a bactericidal agent for oral cavity. Can be given at the same time, further improvement of the prevention or suppression effect of caries is expected.

  However, in particular, in liquid oral compositions such as mouthwashes that are treated in a short period of time of several tens of seconds compared with toothpaste, etc., fluoride as an active ingredient remains in the oral cavity. In addition, it is difficult to provide a continuous bactericidal effect against the caries-causing bacteria in the oral cavity even if an oral bactericidal agent is added. However, the current situation is that they are not compatible.

  Regarding the improvement of the fluoride persistence and the effect of promoting remineralization, Japanese Patent Application Laid-Open No. 2008-156251 discloses that sodium fluoride, a water-soluble calcium salt and a water-soluble magnesium salt are appropriately used for the mouthwash. The technique which mix | blended and combined with the mixture ratio is proposed, and patent document 2 (Unexamined-Japanese-Patent No. 2011-126788) mix | blends monofluorophosphate, calcium glycerophosphate, and a specific polymer in liquid preparations, such as a mouthwash. However, they do not mention the persistence of the bactericidal effect.

  On the other hand, a cationic bactericide as an oral bactericide not only has high bactericidal activity against caries-causing bacteria, but also its bactericidal effect is expressed by adsorbing on the tooth surface, etc. There is a problem that the bactericidal activity is easily deactivated due to the influence, and the adsorptivity is also easily lowered.

  Regarding the improvement of the adsorption amount of the cationic fungicide on the tooth surface, Patent Document 3 (JP 2009-1511 A), which is a combination of a calcium ion supply substance, a cationic fungicide and a specific surfactant in a liquid oral composition. Patent Document 4 (Japanese Patent Laid-Open No. 2011-140454) proposes a technique in which an oral composition is combined with a cationic bactericide and calcium glycerophosphate. However, these are not sufficient in terms of sustainability of the bactericidal effect and have room for improvement.

JP 2008-156251 A JP 2011-126788 A JP 2009-1511 A JP 2011-140454 A JP2013-129620A

  Therefore, in the liquid oral composition, it has been desired to develop a technique capable of achieving both an excellent remineralization promoting effect and a sustained sterilizing effect against caries-causing bacteria.

  The present invention has been made in view of the above circumstances, and provides a liquid oral composition that has an excellent remineralization promoting effect and a continuous sterilizing effect against caries-causing bacteria, and is effective in preventing or suppressing caries. The purpose is to do.

  As a result of intensive studies to achieve the above object, the present inventors have found that (A) sodium fluoride, (B) calcium glycerophosphate, (C) condensed phosphoric acid or a salt thereof, (D) ) Cationic fungicide with a specific amount and a combination of mass ratios of {(B) component + (C) component} / (D) component in a specific ratio, thereby providing excellent remineralization promoting effect and caries cause The present invention has been found that a liquid preparation that is compatible with a highly durable bactericidal effect against bacteria, has a good taste, low irritation and good usability, and is effective in preventing or suppressing dental caries, and the present invention. It came to make.

More specifically, even if a fluoride such as sodium fluoride or a cationic bactericidal agent is added to the liquid oral composition, a sufficient remineralization promoting effect and a continuous bactericidal effect cannot be provided. In the invention, when the components (A), (B), (C), (D) are combined, the mass ratio of {(B) component + (C) component} / (D) component is within a specific range, ( By the B) and (C) components, the remineralization promoting effect derived from the (A) component is enhanced, and at the same time, the sustainability of the sterilizing effect of the (D) component is markedly improved. In this case, although the addition of an anionic substance may lead to a decrease in the activity of the cationic fungicide, when the components (B) and (C), which are anionic substances, are used in combination, both components are specific and synergistic. Surprisingly, a high bactericidal effect is maintained without lowering the bactericidal power of the cationic fungicide of the component (D), and the above-mentioned remarkable remarkable effects are exhibited.
That is, as shown in a comparative example described later, if the component (B) is not blended, the recalcification promoting effect is low even if the component (C) is blended together with the components (A) and (D). The bactericidal effect does not last, and if the (C) component is not blended, the remineralization promoting effect is low and the bactericidal effect even if the (B) component is blended together with the (A) and (D) components. The sustainability is poor. Furthermore, if the mass ratio of {(B) component + (C) component} / (D) component is inappropriate, (B) and (C) components are blended together with (A) and (D) components. However, the persistence of the bactericidal effect is lowered. On the other hand, as shown in the below-mentioned Example, it mix | blends combining (A), (B), (C), (D) component, and {(B) component + (C) component} / ( D) When the mass ratio of the component is within a specific range, the remineralization promoting effect and the sterilization power persistence are improved, and the recalcification promoting effect that can promote the remineralization of teeth at a high rate and the caries cause Sustained bactericidal effect against Streptococcus mutans bacteria, both of which are compatible.
In addition, according to the present invention, a liquid oral composition such as a mouthwash that strongly develops an unpleasant taste and irritation in the oral cavity has astringency, bitterness, off-taste or irritation (B), (C ), (D) Even if it mix | blends component, a favorable usability | use_condition is given, a usability | use_condition is kept favorable and a remineralization promotion effect and a continuous disinfection effect can be made compatible.

  Patent Document 5 (Japanese Patent Application Laid-Open No. 2013-129620) is a technique for improving the feeling of use by suppressing the irritation and the like of an oral composition containing glycerophosphoric acid or a salt thereof. Dentifrice and mouthwash (both oil phase and water layer) contain sodium fluoride, calcium glycerophosphate, condensed phosphate, cationic fungicide, but calcium glycerophosphate and condensation for cationic fungicide The blending ratio of phosphate is as large as 350. Recalling from Patent Document 5 that the {(B) component + (C) component} / (D) component mass ratio of the present invention is 50 or less and the remineralization promoting effect and the sterilization effect are improved. Can not.

Accordingly, the present invention provides the following liquid oral composition.
(A) Sodium fluoride 0.005-0.21 mass%,
(B) calcium glycerophosphate 0.005-1 mass%,
(C) condensed phosphoric acid or its salt 0.05-0.5 mass%,
(D) Cationic fungicide 0.005-0.1% by mass
A composition for liquid oral cavity, wherein the {(B) component + (C) component} / (D) component is 0.5 to 50 in terms of mass ratio.

  ADVANTAGE OF THE INVENTION According to this invention, the composition for liquid oral cavity effective in the prevention or control of a caries which has the outstanding remineralization promotion effect and the continuous bactericidal effect with respect to a caries causative microbe can be provided.

  The present invention will be described in further detail below. The liquid oral cavity composition of the present invention contains (A) sodium fluoride, (B) calcium glycerophosphate, (C) condensed phosphoric acid or a salt thereof, and (D) a cationic fungicide.

(A) Sodium fluoride is present as fluoride ions in the preparation, thereby promoting tooth remineralization.
The blending amount of sodium fluoride is 0.005 to 0.21% (mass%, the same applies hereinafter) of the entire composition, preferably 0.01 to 0.1%, more preferably 0.01 to 0. .05%. Remineralization can be promoted as the blending amount increases. However, if it is less than 0.005%, the remineralization promoting effect is not improved even when combined with the components (B) and (C). If it exceeds 0.21%, the risk of accidental ingestion increases, resulting in poor safety.

  In the present invention, by combining (B) calcium glycerophosphate and (C) condensed phosphoric acid or a salt thereof, the remineralization promoting effect of component (A) is enhanced and the sterilizing power of component (D) is improved. Sustainability is greatly improved.

(B) The calcium glycerophosphate can be used from a natural product or a synthetic product, and for example, a commercial product such as a trade name “Calcium glycerophosphate” manufactured by Iwaki Pharmaceutical Co., Ltd. can also be used.
(B) The compounding quantity of the calcium glycerophosphate of a component is 0.005-1% of the whole composition, Preferably it is 0.01-0.2%. If it is less than 0.005%, the remineralization promoting effect and the sustainability of the bactericidal power are not improved. When it exceeds 1%, the astringent taste / taste of the component (B) itself is strongly expressed and the feeling of use is impaired.

(C) Examples of condensed phosphoric acid include linear polyphosphoric acid such as pyrophosphoric acid, tripolyphosphoric acid, and tetrapolyphosphoric acid, and cyclic polyphosphoric acid such as trimetaphosphoric acid and tetrametaphosphoric acid. Examples include potassium salts. These may be used alone or in combination of two or more. Of these, linear polyphosphates are preferable, and sodium tripolyphosphate and sodium pyrophosphate are particularly preferable.
A commercial item can be used for these condensed phosphoric acids or salts thereof.

  (C) The compounding quantity of the condensed phosphoric acid or its salt of a component is 0.05 to 0.5% of the whole composition, Preferably it is 0.1 to 0.3%. If it is less than 0.05%, the remineralization promoting effect and the sustainability of the bactericidal effect are not improved. If it exceeds 0.5%, irritation to the oral mucosa derived from the component (C) is strongly expressed and the usability is impaired.

  Examples of the (D) cationic fungicide include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine, and the like, and one of these can be used alone or two or more of them can be used in combination. Among them, cetylpyridinium chloride and benzethonium chloride, particularly cetylpyridinium chloride are preferable from the viewpoint of interaction with the component (B), sustainability of bactericidal power, and usability.

  (D) The compounding quantity of a cationic disinfectant is 0.005-0.1% of the whole composition, Preferably it is 0.01-0.08%. As the blending amount increases, the bactericidal power increases, but if it is less than 0.005%, the durability of the bactericidal power does not improve even when combined with the components (B) and (C). If it exceeds 0.1%, the astringency, bitterness and irritation derived from the component (D) are strongly expressed and the feeling of use is impaired.

  In the present invention, the {(B) component + (C) component} / (D) component indicating the blending ratio of the (B) and (C) components and the (D) component is 0.5 to 50 as a mass ratio. Yes, preferably 1-25. If the {(B) component + (C) component} / (D) component is less than 0.5, even if the (B) and (C) components are combined with the (D) component, the sustainability of the bactericidal effect is not sufficiently exhibited. When 50 is exceeded, the components (B) and (C) are combined with the component (D) to form a complex with an anion and a cation, thereby inhibiting the activity of the bactericide and lowering the durability of the bactericidal effect.

  Furthermore, in this invention, it is preferable to use (B) component and (C) component together in a suitable ratio. In this case, the (C) component / (B) component indicating the blending ratio of the (B) and (C) components is preferably 0.1 to 50, more preferably 0.5 to 30 as the mass ratio. Within this range, the remineralization promoting effect and the durability of the bactericidal effect are more excellent. If it is less than 0.1, the sustainability of the remineralization promoting effect and the bactericidal effect may not be sufficiently improved. If it exceeds 50, no further improvement in the effect can be expected, which may be disadvantageous economically.

  The liquid oral composition of the present invention may further contain a liquid medium. A preferred liquid medium is water. The water content is usually 60% or more of the whole composition, preferably 60 to 95%.

Furthermore, a liquid medium other than water may be added as the liquid medium. Examples of the liquid medium that can be used with water include polyhydric alcohols that are liquid at 20 ° C. such as glycerin, propylene glycol, and polyethylene glycol, and lower monohydric alcohols having 2 or 3 carbon atoms such as ethanol.
The polyhydric alcohol is preferably added because it acts as a wetting agent, and its content is preferably 1 to 20%, particularly 3 to 15% of the entire composition.
When the lower monohydric alcohol is added, the content thereof is preferably 20% or less, particularly preferably 10% or less of the entire composition. The lower monohydric alcohol is suitable for imparting a refreshing feeling and a refreshing feeling when used, but if the content exceeds 20%, the irritation becomes strong and the feeling of use may be lowered. In addition, an alcohol-free preparation substantially free of lower monohydric alcohol (content is 0.1% or less of the entire composition) is suitable as a hypoallergenic preparation.

  The liquid oral composition of the present invention is a liquid oral composition such as a mouthwash or liquid dentifrice in which the blended components are solubilized, that is, each component is uniformly dissolved without causing liquid separation or precipitation of insoluble components. It is suitably prepared as a preparation. Alternatively, it may be a preparation in which the compounding ingredients are uniformly dispersed, and a known prepared emulsion (for example, an emulsion similar to the liquid oral composition described in International Publication No. 2011/055888, JP-A-2015-89870, Specifically, NIKKOL NET-TE-50 manufactured by Nikko Chemicals Co., Ltd.) can be added to prepare an emulsion preparation. In addition, the addition amount of the emulsion is preferably 0.1 to 4% of the entire composition.

  The composition of the present invention is a mouthwash of a type that is used as a stock solution, a mouthwash such as a mouthwash that is diluted at the time of use in a concentrated type, a liquid dentifrice or mouthwash that is used by brushing with a toothbrush, a mouth spray However, it is particularly suitable as a mouthwash. In this case, in addition to the above-described components, other known components suitable for the form, dosage form, and the like can be blended as necessary within a range not impeding the effects of the present invention. Specifically, a wetting agent, a thickening agent, a surfactant and, if necessary, a sweetening agent, a coloring agent, a fragrance, an active ingredient, a pH adjusting agent and the like are blended. In addition, it is preferable that solid components which do not solubilize, such as an abrasive | polishing agent, are not normally mix | blended with a liquid oral composition, and an abrasive | polishing agent is not included.

  As the wetting agent, in addition to the polyhydric alcohol, sugar alcohols such as sorbitol, malt, and lactit may be blended, and the blending amount is 2 to 20% of the total composition including the polyhydric alcohol. In particular, 3 to 15% is preferable.

  Examples of the thickener include cellulose derivatives such as sodium carboxymethyl cellulose and cationized cellulose, xanthan gum, sodium alginate and the like. The amount is usually 0 to 5%, particularly 0.01 to 4% of the whole composition.

As the surfactant, a known anionic surfactant, nonionic surfactant, cationic surfactant, or amphoteric surfactant can be blended.
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, for example, sugar alcohol fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester, maltitol fatty acid ester, lactol fatty acid ester, polyoxyethylene fatty acid ester such as polyoxyethylene hydrogenated castor oil, and alkylol amide. And polyoxyethylene sorbitan fatty acid ester, polyglycerin fatty acid ester, hexaglyceryl monocetylate, fatty acid diethanolamide, sorbitan fatty acid ester, polyoxyethylene higher alcohol ether and the like.
Examples of the cationic surfactant include alkyl ammonium and alkyl benzyl ammonium salts, and examples of the amphoteric surfactant include betaine acetate type and imidazoline type.

As the surfactant, nonionic surfactants, in particular, polyoxyethylene hydrogenated castor oil and / or polyoxyethylene alkyl ether, particularly polyoxyethylene hydrogenated castor oil are preferable in terms of appearance stability. is there. The polyoxyethylene hydrogenated castor oil has an average addition mole number of ethylene oxide (hereinafter abbreviated as EO) of 60 to 100 moles, and the polyoxyethylene alkyl ether has 16 to 18 carbon atoms of an alkyl group. O. The average added mole number of 20 to 40 moles is preferable. Specific examples of the polyoxyethylene hydrogenated castor oil include NIKKOL HCO series manufactured by Nikko Chemicals Co., Ltd., Emarex HC series manufactured by Nihon Emulsion Co., Ltd., UNIOX HC series manufactured by NOF Corporation, etc. Commercially available products such as Emarex 100 series and Emarex 600 series manufactured by Nikko Chemicals Co., Ltd. can be used as the ethylene alkyl ether.
The blending amount of these surfactants is preferably 0.05 to 5% of the entire composition.

  Examples of the sweetening agent include xylitol, maltitol, saccharin, sodium saccharin, stevioside, aspartame and the like. As a colorant, a highly safe water-soluble pigment such as Blue No. 1, Green No. 3, Yellow No. 4, Red No. 105, or the like can be added.

  As a fragrance, natural essential oils such as peppermint oil, spearmint oil, eucalyptus oil, winter green oil, clove oil, thyme oil, sage oil, cardamom oil, rosemary oil, marjoram oil, lemon oil, lavender oil, paracres oil, And l-menthol, l-carvone, orange oil, anethole, 1,8-cineole, methyl salicylate, eugenol, thymol, linalool, limonene, menthone, eugenol, menthyl acetate, citral, camphor, borneol, pinene, spirantol, etc. Perfume ingredients contained in natural essential oils, ethyl acetate, ethyl butyrate, isoamyl acetate, hexanal, hexenal, methyl anthranilate, ethyl methyl phenyl glycidate, benzaldehyde Perfume ingredients such as, furaneol, maltol, ethyl maltol, gamma / delta decalactone, gamma / deltown decalactone, N-ethyl-p-menthane-3-carboxamide, menthyl lactate, ethylene glycol 1-menthyl carbonate, One of the flavors of apple, banana, strawberry, blueberry, melon, peach, pineapple, grape, muscat, wine, cherry, squash, coffee, brandy, yogurt, etc. Or 2 or more types can be added in the range which does not inhibit the effect of this invention. The addition amount is usually 0.00001 to 3% in the composition.

  Active ingredients include, for example, enzymes such as dextranase and mutanase, nonionic fungicides such as isopropylmethylcellulose, polyglutamate, allantoin or derivatives thereof, azulene, lysozyme chloride, vitamins such as ascorbic acid, glycyrrhetin salts, chlorophyll Copper chlorophyllin sodium, thyme and other plant extracts, copper gluconate, potassium nitrate, aluminum lactate and the like can be added. In addition, the addition amount of these active ingredients can be made into effective amount in the range which does not prevent the effect of this invention.

  Examples of the pH adjuster include citric acid, tartaric acid, malic acid, phosphoric acid, carbonic acid and their potassium salts, sodium salts, ammonium salts, ribonucleic acid and salts thereof, and sodium hydroxide. In the present invention, the pH of the composition at 25 ° C. is preferably adjusted to 5.5 to 8.0, particularly 6.0 to 7.5, and citric acid and sodium citrate are combined as a pH adjusting agent in the vicinity thereof. Are particularly preferred.

  EXAMPLES Hereinafter, although an Example, a comparative example, a formulation example is 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 (mouthwashes) having the compositions shown in Tables 1 to 4 were prepared by conventional methods and evaluated by the following methods. The results are shown in the table.

(1) Evaluation method of remineralization promoting effect The following experiment was conducted according to the description of Oshino Kazushi et al., Journal of Oral Hygiene 54: 2-8,2004.
Preparation of decalcified sample:
The enamel portion of the bovine teeth was divided into crosses with a hard tissue cutting machine (Isomet 2000, manufactured by Bühler), and four enamel blocks were produced per tooth. The enamel surfaces of these blocks were mirror polished and coated with nail enamel so that an approximately 4 × 4 mm window was exposed. The enamel block was immersed in a decalcification solution having the following composition and allowed to stand at 37 ° C. for 3 days to form an artificial surfaced demineralized lesion.
Composition of decalcification solution: (pH 4.5)
CaCl ₂ 3.0 mmol / L
KH ₂ PO ₄ 1.8 mmol / L
Lactic acid 20mmol / L
Sodium lactate 80mmol / L
Hydroxyethyl cellulose (Wako Pure Chemical Industries, Ltd.) 5.0%
(Adjusted to 1 L with distilled water to the above concentration.)

Remineralization treatment:
Demineralized samples (5 blocks for each group) were immersed in the test compositions of Tables 1 to 4 for 5 minutes twice a day (around 9 o'clock and 18 o'clock). The decalcified sample after immersion was cleaned for about 30 seconds under running tap water after cleaning the window surface for about 10 strokes with a toothbrush (PC CLINICA IONHABRUSH Standard, manufactured by Lion Co., Ltd.), and then one block at a time. It was immersed in 10 mL of remineralization solution having the following composition and maintained at 37 ° C. This remineralization solution is similar to the plaque fluid composition 30 minutes after ingestion of sucrose and is supplemented with acid phosphatase having MFPase activity (derived from P-3627 wheat). . This series of operations continued for 14 days.
Composition of remineralization solution: (pH 6.0)
CaCl ₂ 2.0 mmol / L
KH ₂ PO ₄ 10 mmol / L
Lactic acid 40mmol / L
NaCl 30 mmol / L
KOH appropriate amount acid phosphatase (manufactured by Sigma-Aldrich Japan)
0.025 units / mL
(Adjusted to 1 L with distilled water to the above concentration.)

Measurement of mineral loss by Contact microradiography (CMR):
The sample after decalcification and remineralization treatment was resin-embedded (Rigolac 2004: Permec N: Promoter E = 120: 1: 1, manufactured by Oken Shoji Co., Ltd.) and solidified, and then a hard tissue cutting machine (Isomet 2000) , Manufactured by Buehler Co., Ltd.) to a thickness of 300 μm, and an automatic polishing machine (Speed Wrap ML-150DC, manufactured by Marto Co., Ltd.) was used to prepare a polished slice sample having a thickness of about 150 μm. Each section was subjected to CMR imaging (SO-343) together with an aluminum step for a calibration curve using a soft X-ray generator (CMR-III, manufactured by Softex) under conditions of a current of 3 mA, a voltage of 20 kV, and an X-ray irradiation time of 20 minutes. , Manufactured by Kodak). Under a microscope (OPTIPHOTO T2, manufactured by Nikon), a CMR image of the subsurface demineralized portion was photographed with a camera (HD camera model HQ-130, manufactured by Nikon), and image analysis software (WinRoof V3.0, manufactured by Mitani) ) Was used to analyze the mineral concentration from the enamel surface to the deep. The background and healthy enamel mineral concentrations were set to 0 and 100%, respectively, and from these mineral concentration profiles, the amount of mineral loss (ΔZ; vol% · μm) of the polished slice sample was measured and calculated.
The demineralized sample and the amount of mineral loss ΔZ after remineralization were measured, the remineralization rate of each group was calculated, and the remineralization promoting effect was evaluated according to the following criteria. ○ The above was accepted.

Evaluation criteria for remineralization promoting effect:
◎: Remineralization rate is 60% or more ○: Remineralization rate is 50% or more and less than 60% Δ: Remineralization rate is 40% or more and less than 50% ×: Remineralization rate is less than 40%

(2) Method for evaluating sustainability of bactericidal power Preparation of bacterial solution:
Frozen stock Streptococcus mutans (S. mutans 25175) was dispersed in 4 mL of a medium (TSB: Tolyotropic Soy Blot) with a platinum loop and cultured at 37 ° C. under anaerobic conditions for 24 hours. The resultant was dispersed in 4 mL of another TSB medium and cultured again at 37 ° C. under anaerobic conditions for 24 hours.
Evaluation of durability of bactericidal activity against hydroxyapatite (HAP) powder:
10 mg of HAP powder was weighed into each well of a 96-well plate, washed with 200 μL of 10 mM phosphate buffer (PBS) at pH 7.0, and then immersed in 200 μL of PBS overnight.
Measurement of MIC (Minimum Growth Inhibitory Concentration):
The PBS-treated HAP powder was washed twice with 200 μL of PBS, 150 μL of sterilized saliva was added, and the wells were sealed and rotated at room temperature at 5 rpm for 30 minutes. Remove saliva, add 100 μL of sample, rotate again for 30 minutes, remove excess sample, wash 3 times with 200 μL of PBS, 200 μL for well containing HAP powder, 100 μL for other well PBS was added. After 1 hour, with dilution, including HAP powder with dilution, add 100 μL of PBS to each well, add 10 μL of the above bacterial solution, and gently agitate for 24 hours under anaerobic conditions at 37 ° C. Then, the MIC (minimum growth inhibitory concentration) was determined with the naked eye, and the bactericidal activity was evaluated according to the following criteria. ○ The above was accepted.

Evaluation criteria for sustainability of sterilization power:
◎: MIC is 100 times or more ○: MIC is 60 times or more and less than 100 times △: MIC is 30 times or more and less than 60 times ×: MIC is less than 30 times

(3) Evaluation method of feeling of use (astringency, bitterness, unpleasant taste, no irritation) About 10 mL of sample (liquid oral composition) is included in the mouth, rinsed for 30 seconds, and then astringency, bitterness, The following 4 levels were evaluated for taste and absence of irritation. The average score of 10 people was indicated by ◎, ○, Δ, × according to the following evaluation criteria. ○ The above was accepted.
Usability rating criteria:
4 points: No astringency, bitterness, off-taste, or irritation.
3 points: Almost no astringency, bitterness, off-taste or irritation.
2 points: Slightly astringent, bitter, off-flavor, or irritating.
1 point: There was considerable astringency, bitterness, nasty taste, and irritation.
Usability evaluation criteria:
◎: 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

Details of the raw materials used are shown below.
Sodium fluoride (manufactured by Stella Chemifa Corporation)
Calcium glycerophosphate (Iwaki Pharmaceutical Co., Ltd.)
Sodium tripolyphosphate (manufactured by Taihei Chemical Industry Co., Ltd.)
Sodium pyrophosphate (manufactured by Taihei Chemical Industry Co., Ltd.)
Cetylpyridinium chloride (manufactured by Wako Pure Chemical Industries, Ltd.)
Benzethonium chloride (High amine: Lonza Japan)
Polyoxyethylene (POE) (60) hydrogenated castor oil (manufactured by Nippon Emulsion Co., Ltd.)
Polyoxyethylene (POE) (100) hydrogenated castor oil (manufactured by Nippon Emulsion Co., Ltd.)
Propylene glycol (Asahi Glass Co., Ltd.)
Glycerin (85%, manufactured by Sakamoto Pharmaceutical Co., Ltd.)
Xylitol (Rocket Fleure)
Citric acid (manufactured by Fuso Chemical Industry Co., Ltd.)
Sodium citrate (manufactured by Fuso Chemical Industry Co., Ltd.)
For other ingredients, those conforming to the Quasi-drug Raw Material Standard 2006 were used.

Next, Table 5 shows a prescription example. The composition of the fragrance composition A used is as shown in Tables 6 to 12, the cationized cellulose is Leogard GP (manufactured by Lion Corporation), and the emulsion is NIKKOL NET-TE-50 (manufactured by Nikko Chemicals Corporation). used.
The liquid oral compositions of the formulation examples were all excellent in the remineralization promoting effect and the sustainability of the bactericidal power, and the feeling of use (astringency / bitterness / taste / no irritation) was also good.

＊；香料組成物Ａ０．２％中に、ｌ−メントール０．０３％を含む（いずれも組成物全体に対する含有量）。

*: In fragrance composition A 0.2%, 1-menthol 0.03% is contained (both are contents relative to the whole composition).

（表中、部は質量部である（以下同様。）。）

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

Claims (5)

(A) Sodium fluoride 0.005-0.21 mass%,
(B) calcium glycerophosphate 0.005-1 mass%,
(C) condensed phosphoric acid or its salt 0.05-0.5 mass%,
(D) Cationic fungicide 0.005-0.1% by mass
A composition for liquid oral cavity, wherein the {(B) component + (C) component} / (D) component is 0.5 to 50 in terms of mass ratio.   The liquid oral composition according to claim 1, wherein the component (D) is cetylpyridinium chloride and / or benzethonium chloride.   The liquid oral composition according to claim 1 or 2, wherein the component (C) is sodium tripolyphosphate and / or sodium pyrophosphate.   Furthermore, (C) component / (B) component is 0.1-50 as mass ratio, The composition for liquid oral cavity of Claim 1, 2 or 3.   The composition for liquid oral cavity according to any one of claims 1 to 4, which is prepared as a mouthwash.