JP2008156308A - Composition for oral cavity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for oral cavity, having high antibacterial effect against oral biofilm, exhibiting excellent effect for reducing and preventing oral diseases such as dental caries, periodontosis and halitosis, and having reduced bitter taste and disagreeable taste. <P>SOLUTION: The invention provides a composition for oral cavity containing (A) an alkyldiaminoethylglycine hydrochloride, (B) an N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidonecarboxylic acid salt and (C) raffinose, wherein the mass ratio of the component C to the sum of the components A and B is ≥1, and the above composition for oral cavity further containing (D) a polyoxyethylene hardened castor oil having an average addition molar number of ethylene oxide of 60-100 mol. The composition has high effect to suppress the oral cavity biofilm causing oral cavity diseases, exhibits excellent effect for reducing and preventing oral diseases such as gingivitis, periodontosis, dental caries and halitosis, having reduced bitter taste and disagreeable taste and giving good feeling in use. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention has a high bactericidal effect on oral biofilm (dental plaque) that is the cause of oral diseases, is excellent in reducing and preventing oral diseases such as caries, periodontal disease, bad breath, etc. The present invention relates to a composition for oral cavity with reduced bitterness and taste.

  In recent years, dental plaque has been regarded as a biofilm, and phenolic fungicides (Patent Document 1) and the like have been developed as a sterilization means so far, but bacteria in biofilm have a strong drug resistance mechanism, This alone is not enough to suppress the biofilm, and it has been difficult to reduce the risk of oral disease.

  Patent Document 2 discloses a composition of oral gluconate, copper citrate and alkyldiaminoethylglycine hydrochloride as an oral composition having excellent antibacterial activity and bad breath prevention effect, and Patent Document 3 describes chemicals of tongue coating. As a liquid oral composition for removal, a blending composition of condensed phosphate and alkyldiaminoethylglycine hydrochloride is proposed, and Patent Document 4 discloses a dentifrice composition that gives gloss to teeth blended with wax and alkyldiaminoethylglycine hydrochloride. , Patent Document 5 contains a toothpaste composition that gives gloss to teeth containing shellac and alkyldiaminoethylglycine hydrochloride, and Patent Document 6 contains an oral cavity composition that contains palatinit and dodecyldiaminoethylglycine, which provides an effect of suppressing halitosis and bitterness. Compositions have been proposed.

  Patent Document 7 discloses an anti-endotoxin agent containing N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate as an active ingredient, and an oral composition for periodontal disease suppression containing the same. Has been proposed. In Patent Document 8, a cationic bactericide such as cetylpyridinium chloride or chlorhexidine gluconate and an N-long chain acyl basic amino acid lower alkyl ester or a salt thereof are blended to adjust the pH to 5.5 to 6.5. Composition for oral cavity in which the amount of adsorbent adsorbed to apatite is increased, Patent Document 9 discloses a composition for oral cavity containing a cationic fungicide and a nonionic surfactant. An oral composition having an excellent bactericidal effect and a good taste, which contains an alkyl ester or a salt thereof, has been proposed. Patent Document 10 proposes an oral composition that can control bactericidal bacteria and contribute to systemic health, containing a bactericide and an N-long chain acyl basic amino acid lower alkyl ester or a salt thereof. . Patent Document 11 discloses that a cationic surfactant and a resinoid are combined and blended in order to suppress bitterness caused by the cationic surfactant.

  However, in these technologies, when many antibacterial components are blended in order to exert a high biofilm inhibitory effect, the feeling of use is reduced due to the bitterness and off-flavor derived from the antibacterial components, both of which have a strong biofilm inhibitory action. It has been difficult to obtain a product having a high bactericidal effect on oral biofilm and a good feeling of use due to problems such as taste and taste. Therefore, development of an oral composition that has excellent biofilm inhibitory action against oral biofilm (dental plaque) that is the cause of oral disease, is excellent in reducing and preventing various oral diseases, and also has good palatability Is desired.

JP 02-11511 A Japanese Patent No. 2540892 JP-A-11-209257 JP 2000-143469 A JP 2000-154128 A JP 2000-281545 A JP 2005-104913 A JP-A-9-286712 JP-A-11-255629 JP 2000-256155 A JP 2001-072562 A

  The present invention has been made in view of the above circumstances, has a high bactericidal effect on oral biofilms (dental plaques) that are the cause of oral diseases, and reduces and prevents oral diseases such as caries, periodontal disease and bad breath. An object of the present invention is to provide a composition for oral cavity which is excellent in effect and has a good feeling of use due to reduced bitterness and off-flavor derived from bactericidal components.

  As a result of intensive studies to achieve the above object, the present inventor has (A) alkyldiaminoethyl glycine hydrochloride, (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate, , (C) raffinose with respect to the total amount of (A) alkyldiaminoethylglycine hydrochloride and (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate (C) raffinose Are blended so as to have the same mass or more, more preferably (D) by adding polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 60 to 100 moles, it is high for oral biofilm It has been found that an oral composition that exhibits a bactericidal effect and has almost no bitterness or off-taste and an excellent usability can be obtained.

Alkyldiaminoethylglycine hydrochloride has a sour bitter taste, and N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate has an odd bitter taste.
The present inventor has a bactericidal effect on oral biofilm (dental plaque) by blending alkyldiaminoethylglycine hydrochloride and N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate as antibacterial components. Although it is exhibited, its bactericidal effect is not yet sufficient, and both of these components have a bitter or unpleasant taste, but there are problems in terms of feeling of use. (A) Alkyldiaminoethylglycine hydrochloride and (B) When (C) raffinose is used in combination at a specific ratio with respect to the total amount of N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate, as is clear from the experimental results described below, The antibacterial action derived from the components (A) and (B) is remarkable due to the synergistic action with the components (A), (B) and (C). And antibacterial activity against both Gram-positive and Gram-negative bacterial species that are resident in the oral cavity, exhibiting a high bactericidal effect on oral biofilm, and (A) alkyl hydrochloride Bitterness and off-taste derived from diaminoethyl glycine and (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate are reduced, so that palatability is also improved, and therefore, causes of oral diseases It has a high bactericidal effect on a certain oral biofilm, is excellent in reducing and preventing oral diseases such as caries, periodontal disease, and bad breath, and can provide an oral composition having a good feeling of use. It has been found and the present invention has been made.

  Accordingly, the present invention comprises (A) alkyldiaminoethylglycine hydrochloride, (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate, and (C) raffinose, and ( The composition for oral cavity, wherein the compounding amount of component (C) is 1.0 or more by mass ratio with respect to the total compounding amount of component A) and component (B), and (D) ethylene Provided is a composition for oral cavity characterized by containing polyoxyethylene hydrogenated castor oil having an average added mole number of oxide of 60 to 100 moles.

  The oral composition of the present invention has a high effect of suppressing oral biofilms that cause oral diseases, is excellent in reducing and preventing oral diseases such as gingivitis, periodontal disease, dental caries, bad breath, and bitterness And taste is suppressed and the feeling of use is also good.

  Hereinafter, the present invention will be described in more detail. The composition for oral cavity of the present invention comprises (A) alkyldiaminoethylglycine hydrochloride and (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylic acid. Salt and (C) raffinose.

(A) Alkyldiaminoethylglycine hydrochloride is a kind of amphoteric surfactant that does not significantly reduce bactericidal activity even in the presence of protein, and has a strong bactericidal effect both acidic and basic.
In the present invention, as alkyldiaminoethylglycine hydrochloride, those having an alkyl group having 12 to 14 carbon atoms are preferably used. For example, lauryldiaminoethylglycine hydrochloride, myristyldiaminoethylglycine hydrochloride, or hydrochloric acid containing these as the main components There is coconut oil alkyldiaminoethylglycine.
As such alkyl hydrochloride (C ₁₂ H _{25 to} C ₁₄ H ₂₉ ) diaminoethylglycine, a commercially available product can be used. Specifically, 40% alkyldiaminoethylglycine hydrochloride aqueous solution (“Levon 40” manufactured by Sanyo Chemical Industries, Ltd.) ).

  The blending amount of alkyldiaminoethylglycine hydrochloride is preferably 0.01 to 0.5% (mass%, the same applies hereinafter) of the total composition, more preferably 0.01 to 0, from the viewpoint of the bactericidal effect on the biofilm. 0.3%, more preferably 0.01-0.2%. When the blending amount is less than 0.01%, a sufficient biofilm suppressing effect may not be obtained. When the blending amount exceeds 0.5%, it may be insufficient in terms of flavor such as bitterness.

  (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate is a kind of amino acid L-arginine, plant-derived palm oil fatty acid, ethanol, and pyrrolidone which is a natural moisturizing factor. Cationic surfactant obtained from carboxylic acid and has good antibacterial properties.

  As the N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate, specifically, those commercially available under the trade name “CAE” manufactured by Ajinomoto Co., Inc. can be used.

  The blending amount of N-coconut oil fatty acyl-L-arginine ethyl DL-pyrrolidone carboxylate is preferably 0.01 to 5.0%, more preferably 0.01 to 3.0% of the whole composition, More preferably, it is 0.1 to 3.0%. When the blending amount is less than 0.01%, a sufficient biofilm suppressing effect may not be obtained. When the blending amount exceeds 5.0%, although depending on the blending amount of alkyldiaminoethylglycine hydrochloride, bitterness or the like occurs. May be insufficient in terms of flavor.

Raffinose is a trisaccharide composed of one molecule each of D-galactose, D-glucose and D-fructose, in a form in which galactose is bound to sucrose.
In the present invention, as raffinose, specifically, “Nitten raffinose” manufactured by Nippon Sugar Sugar Co., Ltd., “Meiji Beat Oligo”, “Meiji Beat Oligo FP” manufactured by Meiji Food Materia Co., Ltd., “Oligo GGF” manufactured by Asahi Kasei Chemicals Corporation What is marketed as can be used.

  The blending amount of raffinose is preferably 0.02 to 50%, more preferably 0.02 to 30% of the entire composition. More preferably, it is 0.2 to 20%. When the blending amount is less than 0.02%, there may be cases where a sufficient biofilm suppression effect and bitterness and off-flavor suppression effect may not be obtained, and when it exceeds 50%, the sweetness of the oral composition becomes too strong. There is.

  In the present invention, (A) alkyldiaminoethylglycine hydrochloride, (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate, and (C) raffinose are used as component (A) and component (B). Component (C) is blended so that the blending amount of component (C) is equal to or greater than the total blending amount of components, that is, 1.0 or more in terms of mass ratio. And it is possible to effectively suppress off-flavors. In this case, the ratio of the total amount of (A) alkyldiaminoethylglycine hydrochloride and (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate and (C) raffinose is as follows: The mass ratio is preferably 1: 1.0 to 1:80, particularly 1: 2 to 1:50, and particularly preferably 1: 2 to 1:30. When the blending amount of raffinose is less than 1.0 by mass ratio with respect to the sum of blending amounts of component (A) and component (B), the effect of suppressing the bitterness and taste of the oral composition is insufficient, and biofilm The bactericidal effect on the water is not improved and a high bactericidal effect cannot be obtained. When the amount of component (C) is too large and the mass ratio of component (C) to the total amount of component (A) and component (B) exceeds 80, the sweetness of the oral composition becomes too strong. The feeling may be inferior.

  Furthermore, in the present invention, in addition to the above essential components, (D) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 60 to 100 moles may be blended from the viewpoint of improving the bactericidal effect on the biofilm. preferable. The polyoxyethylene hydrogenated castor oil has various numbers of moles of ethylene oxide (EO) added. The average number of moles of ethylene oxide added to the polyoxyethylene hydrogenated castor oil used in the present invention is the bactericidal effect on the biofilm. 60 to 100 mol is desirable, and 60 mol is particularly preferable. In addition, the polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of less than 60 moles may not improve the bactericidal effect on the biofilm, and the average added mole number of ethylene oxide exceeds 100 moles. Generally not commercially available.

  (D) As for the compounding quantity of polyoxyethylene hydrogenated castor oil, 0.01 to 3.0% of the whole composition is preferable, More preferably, it is 0.1 to 2.0%. More preferably, it is 0.1 to 1.0%. If the blending amount is less than 0.01%, a sufficient biofilm inhibitory effect may not be obtained, and if it exceeds 3.0%, the biofilm inhibitory effect is enhanced, but the flavor of the oral composition is oily. It may become ugly and inferior in use.

  The composition for oral cavity according to the present invention can be made into various forms such as solid, solid, liquid, liquid, gel, paste, gum and the like, such as toothpaste, liquid toothpaste, liquid toothpaste, and toothpaste. It can be prepared in various dosage forms such as dentifrice, mouthwash, mouthwash, etc., and its manufacturing method can adopt a conventional method according to the dosage form, but depending on the purpose, the dosage form of the composition, etc. In addition to the above-described essential components (A) to (C), and in addition to the component (D), the following appropriate optional components can be further blended as other components.

  Specifically, in the case of dentifrice, for example, silica-based abrasives such as precipitated silica, silica gel, aluminosilicate, zirconosilicate, dicalcium phosphate dihydrate and anhydrate, calcium pyrophosphate, Calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, tribasic magnesium phosphate, zeolite, zirconium silicate, synthetic resin-based abrasive and the like are preferably used. The blending amount of these abrasives is preferably 2 to 40%, particularly 10 to 30% of the entire dentifrice composition.

  As a thickener, it is possible to mix | blend 1 type (s) or 2 or more types, such as glycerol, sorbitol, propylene glycol, polyethyleneglycol 200-20000, and xylitol. These blending amounts are preferably 5 to 50%, particularly 20 to 45% of the entire composition.

  Examples of alcohols include monohydric alcohols such as ethanol, isopropanol, butanol and propanol, ethylene glycol, diethylene glycol, hexylene glycol, butylene glycol, pentanediol, and polyhydric alcohols of polypropylene glycol 300 to 4000. It is possible to mix | blend 1 type (s) or 2 or more types. The blending amount is preferably 1 to 30%, particularly 2 to 20% of the whole composition.

  As the binder, one or more of sodium carboxymethylcellulose, hydroxyethylcellulose, carrageenan, sodium alginate, xanthan gum, sodium polyacrylate, carbopol, guar gum, montmorillonite, gelatin and the like can be blended. Although the compounding quantity of a binder can be adjusted with a dosage form, it can be 0.1 to 5% for toothpaste, and can be 0 to 5% for liquid toothpaste and mouthwash.

  Sweeteners include sodium saccharin, xylitol, lactitol, maltitol, erythritol, mannitol, palatinose, reduced palatinose (palatinite), thaumatin, aspartame, acesulfame K, cyclamate sodium, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesberi Contains 1 or 2 or more of zircodihydrochalcone, perilartin, p-methoxycinnamic aldehyde, trehalose, soybean oligosaccharide, dairy oligosaccharide, xylooligosaccharide, L-aspartyl-L-phenylalanine methyl ester, sucralose, glycyrrhizin Is possible.

  As a preservative, it is possible to mix | blend 1 type (s) or 2 or more types, such as p-hydroxybenzoic acid ester, benzoic acid, and a benzoate.

  As the organic acid, various organic acids that can be usually blended in oral compositions can be used, for example, citric acid, isocitric acid, malic acid, acetic acid, oxalic acid, malonic acid, succinic acid, glutaric acid, maleic acid, fumaric acid. Examples thereof include acid, aconitic acid, lactic acid, tartaric acid, pyruvic acid, ascorbic acid, glycolic acid, and salts thereof. Among these, citric acid, malic acid, tartaric acid, lactic acid, or salts thereof are particularly suitable, and one or more can be blended.

As the surfactant, one or more of an anionic surfactant, a nonionic surfactant and an amphoteric surfactant can be blended.
Examples of the anionic surfactant include sodium alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosinate such as sodium N-lauroyl sarcosinate, sodium N-myristoyl sarcosinate, sodium dodecylbenzene sulfonate, Hydrogenated coconut fatty acid monoglyceride sodium monosulfate, sodium lauryl sulfoacetate, N-acyl glutamate such as sodium N-palmitoyl glutamate, N-methyl-N-acyl taurine sodium, N-methyl-N-acylalanine sodium, α-olefin Sodium sulfonate, sodium dioctyl sulfosuccinate and the like are used.

  Nonionic surfactants include sugar fatty acid esters such as sucrose fatty acid esters, maltose fatty acid esters, and lactose fatty acid esters, sugar alcohol fatty acid esters such as maltitol fatty acid esters and lactitol fatty acid esters, and polyoxyethylene sorbitan monolaurate. Polyoxyethylene fatty acid esters such as polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, fatty acid diethanolamides such as lauric acid mono or diethanolamide, myristic acid mono or diethanolamide, sorbitan fatty acid esters, fatty acid monoglycerides, Polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene polyol Dipropylene fatty acid esters and the like are used.

  Zwitterionic surfactants include N-alkyl-lauryldimethylaminoacetic acid betaine, coconut oil fatty acid amidopropyldimethylaminoacetic acid betaine, N-coconut oil fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine sodium, etc. Or it is possible to mix | blend 2 or more types.

  The blending amount of the surfactant as an optional component is preferably 0.1 to 2%, particularly 0.2 to 1% of the entire composition.

  As a medicinal component, in addition to (A) alkyldiaminoethylglycine hydrochloride and (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate, as other medicinal components, for example, sodium azulene sulfonate, ε-aminocaproic acid, allantoin, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, epidihydrocholesterin, dihydrocholesterol, sodium chloride, glycyrrhizic acid, diammonium glycyrrhizinate, disodium glycyrrhizinate, trisodium glycyrrhizinate, dipotassium glycyrrhizinate, Monoammonium glycyrrhizinate, β-glycyrrhetinic acid, isopropylmethylphenol, cetylpyridinium chloride, decalinium chloride, benzalco chloride Nium, benzethonium chloride, chlorhexidine hydrochloride, triclosan, ascorbic acid, sodium ascorbate, pyridoxine hydrochloride, dl-α-tocopherol acetate, dl-α-tocopherol nicotinate, zeolite, disodium dihydrogen pyrophosphate, sodium pyrophosphate, anhydrous pyrroline Sodium phosphate, sodium monohydrogen phosphate, trisodium phosphate, sodium polyphosphate, sodium fluoride, sodium monofluorophosphate, tin fluoride, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol Recall 20000, polyvinylpyrrolidone, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K90, lysozyme chloride, copper chlorophyllin sodium, hinokitiol, polyoxyethylene lauryl ether (average number of added moles of ethylene oxide 8-10), lauroyl sarcosine sodium, tranexam Acid, dextranase, aluminum lactate, potassium nitrate, protease and the like can be blended in one or more kinds depending on the purpose. The compounding quantity of the said medicinal component can be made into an effective quantity in the range which does not prevent the effect of this invention (mixing quantity usually 0.001 to 5%).

  Perfumes include peppermint oil, spearmint oil, anise oil, eucalyptus oil, winter green oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, peppermint oil, cardamom oil, coriander oil, mandarin oil, Lime oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, grapefruit oil, sweetie Natural fragrances such as oil, coconut oil, Iris concrete, absolute peppermint, absolute rose, orange flower, and processing of these natural fragrances (front reservoir cut, rear reservoir cut, fractionation, essence, powdered fragrance, etc.) Perfumed and menthol, carvone, Netol, cineol, methyl salicylate, cinnamic aldehyde, eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted paramentan-3- Carboxamide, pinene, octylaldehyde, citral, pulegone, carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allylcyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, hexanal, Butanol, isoamyl alcohol, hexenol, dimethyl sulfide, cycloten, furfural, trimethylpyrazine, ethyl lactate, ethylthioacete For peroral compositions such as strawberry flavor, apple flavor, banana flavor, pineapple flavor, grape flavor, mango flavor, butter flavor, milk flavor, fruit mix flavor, tropical fruit flavor, etc. The known perfume materials used can be used in combination.

  EXAMPLES Hereinafter, although an experiment example and an Example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, the blending amount is mass%. About the (A) component used for Table 1 and Examples 1-7, the compounding quantity converted into the pure part was shown.

[Experimental example]
About the test solution which mix | blended the chemical | medical agent shown in Table 1, the bactericidal effect with respect to an oral biofilm, the strength of a bitterness, and the presence or absence of a nasty taste were evaluated by the following method, and the bactericidal effect with respect to an oral biofilm was evaluated. The results are shown in Table 1.

Method for evaluating bactericidal effect on oral biofilm:
5 types of oral bacteria, Streptococcus mutans ATCC 25175 strain, Streptococcus sanguinis ATTC 10556 strain, Actinomyces naeslandi ATCC 51655 strain, Fusobacterium nucleatum ATCC 10953 strain and Bayonera parbra ATCC 17745 strain using Biofilm 6 mm, thickness 3 mm). Specifically, inoculate 700 ml of BMM medium (see the following composition) in a continuous culture vessel with hydroxyapatite on a rotating plate so that each of the above bacteria would be 10 ⁷ / ml, and anaerobically cultured at 37 ° C. overnight. did. Thereafter, the BMM medium was continuously supplied to the continuous culture vessel with a pump at 70 mL / hour, and the same amount of the culture solution was discharged with another pump to perform continuous culture. After continuous supply of the medium, the medium was discharged 11 hours and 30 minutes later, replaced with Todd Hewitt medium (hereinafter abbreviated as THB, Becton Dickinson) containing 1% sucrose, and cultured at 37 ° C. for 30 minutes. The medium was discharged, replaced with 700 mL of BMM medium again, and continuously cultured for 11 hours and 30 minutes. A cycle of culturing with 1% sucrose-added THB for 30 minutes was performed four times to form a biofilm on the hydroxyapatite surface. Hydroxyapatite after biofilm formation is taken out, washed with physiological saline, transferred to a petri dish (diameter 35 mm × height 14 mm), so that the drug shown in Table 1 has a predetermined concentration per hydroxyapatite disk. 5 g of a test solution prepared by dissolving or dispersing in 10 mM phosphate buffer (pH 6) * was allowed to act at 37 ° C. for 1 minute.
* 10 mM phosphate buffer (pH 6): 12.3 mL of 10 mM dipotassium phosphate is added to 87.7 mL of 10 mM monopotassium phosphate and mixed.

In addition, the detail of the chemical | medical agent used for Table 1 and Examples 1-7 is as follows. Alkyldiaminoethylglycine hydrochloride 40% hydrochloric acid alkyl _{(C 12 H 25 ~C 14 H} 29) diamino ethyl glycine aqueous solution (manufactured by Sanyo Chemical Industries, Ltd. "Rebon 40"), N- cocoyl -L- arginine ethyl DL-pyrrolidone carboxylate uses “CAE” manufactured by Ajinomoto Co., Inc. (hereinafter abbreviated as “CAE”), raffinose uses “Nitten Raffinose” manufactured by Nippon Sugar Sugar Co., Ltd., polyoxyethylene hydrogenated castor oil is NIKKOL “HCO-50” (polyoxyethylene (50) hydrogenated castor oil), “HCO-60” (polyoxyethylene (60) hydrogenated castor oil), “HCO-80” (polyoxyethylene (made by Nikko Chemicals Co., Ltd.) 80) hydrogenated castor oil), "HCO-100" (polyoxyethylene (100) hydrogenated castor oil) In addition, palatinose as a comparative control product was adjusted to a predetermined concentration with 10 mM phosphate buffer (pH 6) using “Powder Palatinose ICP” manufactured by Mitsui Sugar Co., Ltd.

  After the drug-treated hydroxyapatite was washed twice with physiological saline, it was anaerobically cultured overnight at 37 ° C. in a 24-well plate with 1.5 mL of heart infusion medium (Becton Dickinson). This was washed twice with physiological saline, 2 mL of physiological saline was added, the biofilm was dispersed with an ultrasonic homogenizer, diluted as appropriate, smeared on a THB agar dish, and anaerobically cultured at 37 ° C. for 5 days. Colonies after culture were counted to determine the number of viable bacteria in the biofilm, treated with 10 mM phosphate buffer containing no drug, and 100, and the percentage of each drug-treated group was shown as a percentage.

BMM (Basal Medium Mucin) medium composition;
Proteose peptone ^{* 1} 0.2%
East Extract ^{* 1} 0.1
Tripty case peptone ^{* 1} 0.1
Porcine stomach mucin ^{* 2} 0.25
KCl ^{* 3} 0.05
L-cysteine hydrochloride ^{* 3} 0.01
Water remaining
Total 100.0%
* 1: Nippon Becton Dickinson Co., Ltd.
* 2: Sigma Aldrich Japan Co., Ltd.
* 3: Wako Pure Chemical Industries, Ltd.

<Sensory evaluation method>
For test solutions prepared by dissolving or dispersing the drugs shown in Table 1 in 10 mM phosphate buffer (pH 6), ten subjects (8 males and 2 females) evaluated the strength of bitterness and the presence or absence of taste. And evaluated according to the following evaluation criteria. In addition, 10 mM phosphate buffer was used as a control, and each drug was sensory-evaluated by setting this sensory evaluation to 5 as the strength of bitterness and presence or absence of taste. The result was shown by the average value of the scores of 10 subjects.

Evaluation criteria Bitterness strength:
5: No bitterness 4: Little bitterness 3: Some bitterness 2: Some bitterness 1: Strong bitterness Existence of taste:
5: No nasty taste 4: Almost no nasty taste 3: Slightly unpleasant taste 2: A strange taste 1: Strong taste

  From the results of Table 1, in the combined use of 0.1% alkyldiaminoethyl glycine hydrochloride and 0.1% N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate (Comparative Experimental Example 1), The number of bacteria in the biofilm is only reduced to about 14% of the initial level, and it has a bitter taste and an odd taste and is inferior in use feeling, and raffinose has no biofilm bactericidal effect (Comparative Experimental Example 7). In contrast, when a combination of alkyldiaminoethylglycine hydrochloride, N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate and raffinose (Experimental Examples 1-3), biofilm bactericidal effect is improved. It has been confirmed that the bitterness and off-taste are improved. Even if palatinose is added to the combined composition of alkyldiaminoethylglycine hydrochloride and N-coconut oil fatty acid acyl-L-arginine ethyl / DL-pyrrolidone carboxylate (Comparative Experimental Example 3), the biofilm bactericidal effect is almost none. It was not improved, and the bitterness and taste were not improved satisfactorily.

  Furthermore, the blended composition of alkyldiaminoethylglycine hydrochloride, N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate and raffinose has an average addition mole number of polyoxyethylene hydrogenated castor oil, particularly ethylene oxide. It was found that when 60 to 100 mol of polyoxyethylene hydrogenated castor oil was used in combination (Experimental Examples 4 to 8), a more excellent biofilm sterilization effect was obtained.

  Raffinose, and also polyoxyethylene hydrogenated castor oil, has improved biofilm permeability and retention of alkyldiaminoethylglycine hydrochloride and N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate. It is thought that the bactericidal effect is improved.

  Further, alkyldiaminoethylglycine hydrochloride has a sour bitterness (Comparative Experimental Example 8), and N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidonecarboxylate has an odd bitterness (Comparative Experimental Example). 9) Moreover, even if raffinose is blended in less than the same amount with respect to the total blending amount of alkyldiaminoethylglycine hydrochloride and N-coconut oil fatty acid acyl-L-arginine ethyl / DL-pyrrolidone carboxylate (comparison) Experimental example 2), bitterness and taste cannot be sufficiently suppressed, the taste is not improved, and the biofilm bactericidal effect is also alkyldiaminoethylglycine hydrochloride and N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidonecarboxylic acid Almost no improvement compared to the composition containing salt (Comparative Experimental Example 1), but alkyldiaminoethyl hydrochloride By blending the same amount or more of raffinose with respect to the total amount of glycine and N-coconut oil fatty acid acyl-L-arginine ethyl / DL-pyrrolidone carboxylate (Experimental Examples 1-3), biofilm bactericidal effect It was confirmed that the bitterness and off-taste were sufficiently suppressed and the taste was improved.

  When 0.02% alkyldiaminoethylglycine hydrochloride and 0.5% N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate (Experimental Examples 9 to 13) are used, 0.1% High biofilm bactericidal effect compared to the case of blending alkyldiaminoethylglycine hydrochloride and 0.1% N-coconut oil fatty acid acyl-L-arginine ethyl / DL-pyrrolidone carboxylate (Comparative Experimental Examples 4 to 6) The obtained results were similar to those described above (Experimental Examples 9 to 13 and Comparative Experimental Examples 4 to 6). When 0.2% alkyldiaminoethylglycine hydrochloride, 0.5% N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate and 20% raffinose were used (Experimental Example 14), The highest biofilm bactericidal effect was obtained.

[Example 1] Toothpaste silica 20.0%
Propylene glycol 3.0
Glycerin 25.0
Sodium carboxymethylcellulose 1.4
Alkyldiaminoethylglycine hydrochloride 0.2
N-coconut oil fatty acid acyl-L-arginine ethyl
DL-pyrrolidonecarboxylate 1.0
Raffinose 2.0
Sodium lauryl sulfate 1.2
Saccharin sodium 0.1
Methylparaben 0.1
Sodium fluoride 0.21
Fragrance 0.8
Purified water balance
Total 100.0%

[Example 2] Toothpaste aluminum hydroxide 42.0%
Propylene glycol 3.0
70% sorbit 25.0
Sodium carboxymethylcellulose 1.2
Alkyldiaminoethylglycine hydrochloride 0.08
N-coconut oil fatty acid acyl-L-arginine ethyl
DL-pyrrolidonecarboxylate 1.2
Raffinose 5.0
Sodium lauryl sulfate 1.2
Saccharin sodium 0.1
Methylparaben 0.1
Butylparaben 0.02
Sodium monofluorophosphate 0.73
Fragrance 1.0
Purified water balance
Total 100.0%

[Example 3] Toothpaste heavy calcium carbonate 25.0%
Propylene glycol 3.0
70% sorbit 25.0
Sodium carboxymethylcellulose 1.2
Alkyldiaminoethylglycine hydrochloride 0.3
N-coconut oil fatty acid acyl-L-arginine ethyl
DL-pyrrolidonecarboxylate 0.2
Raffinose 5.0
Sodium lauryl sulfate 1.2
Saccharin sodium 0.1
Methylparaben 0.1
Butylparaben 0.02
Sodium monofluorophosphate 0.73
Fragrance 1.0
Purified water balance
Total 100.0%

[Example 4] Toothpaste silica 15.0%
Propylene glycol 3.0
70% sorbit 25.0
Sodium carboxymethylcellulose 1.2
Alkyldiaminoethylglycine hydrochloride 0.008
N-coconut oil fatty acid acyl-L-arginine ethyl
DL-pyrrolidonecarboxylate 1.2
Raffinose 5.0
Palatinose 2.5
Sodium lauryl sulfate 1.2
Saccharin sodium 0.1
Methylparaben 0.1
Butylparaben 0.02
Sodium monofluorophosphate 0.73
Fragrance 1.0
Purified water balance
Total 100.0%

[Example 5] Toothpaste dicalcium phosphate 40.0%
Propylene glycol 3.0
70% sorbit 25.0
Sodium carboxymethylcellulose 1.2
Alkyldiaminoethylglycine hydrochloride 0.15
N-coconut oil fatty acid acyl-L-arginine ethyl
DL-pyrrolidonecarboxylate 3.0
Raffinose 5.0
Sodium lauryl sulfate 1.2
Saccharin sodium 0.1
Methylparaben 0.1
Butylparaben 0.02
Sodium monofluorophosphate 0.73
Fragrance 1.0
Purified water balance
Total 100.0%

[Example 6] Mouthwash glycerin 5.0%
Ethanol 8.0
Alkyldiaminoethylglycine hydrochloride 0.02
N-coconut oil fatty acid acyl-L-arginine ethyl
DL-pyrrolidonecarboxylate 1.2
Polyoxyethylene hydrogenated castor oil 0.8
(Mole number of ethylene oxide added 100)
Raffinose 3.0
Xylitol 5.0
Sodium citrate 0.1
Citric acid 0.3
Sodium benzoate 0.5
Fragrance 0.2
Purified water balance
Total 100.0%

[Example 7] Mouth freshener glycerin 13.0%
Ethanol 40.0
Polyoxyethylene hydrogenated castor oil 3.0
(Mole number of ethylene oxide added 60)
Alkyldiaminoethylglycine hydrochloride 0.06
N-coconut oil fatty acid acyl-L-arginine ethyl
DL-pyrrolidonecarboxylate 0.2
Raffinose 1.0
Reduced palatinose 1.5
Xylitol 2.0
Sodium citrate 0.1
Citric acid 0.03
Fragrance 0.4
l-Menthol 0.5
Purified water balance
Total 100.0%

  The compositions for oral cavity of these examples were all excellent in bactericidal effect on oral biofilm (dental plaque), and the bitterness / taste was reduced and the usability was good.

Claims (2)

  (A) Alkyldiaminoethylglycine hydrochloride, (B) N-coconut oil fatty acid acyl-L-arginine ethyl DL-pyrrolidone carboxylate, (C) raffinose, and (A) component and (B The composition for oral cavity, wherein the compounding amount of the component (C) is 1.0 or more by mass ratio with respect to the total compounding amount of the component.   The oral composition according to claim 1, further comprising (D) polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 60 to 100 moles.