JP4888636B2 - Dentifrice composition - Google Patents

Description

  The present invention relates to a dentifrice composition having a good foam quality and an excellent effect of suppressing an oral biofilm which is a cause of oral diseases.

  In recent years, dental plaque has been regarded as a biofilm (Non-patent Document 1), and bacteria in the biofilm have a bacterial protein expression pattern (Non-Patent Documents 2 and 3) and drug resistance (Non-Patent Document 1). 4 and 5) are greatly different, and it has become clear that drugs effective against planktonic bacteria are not effective against biofilm-forming bacteria.

  So far, phenolic fungicides (Patent Document 1) and the like have been developed as sterilizing means. However, since bacteria in biofilm have a strong drug resistance mechanism, this alone is not sufficient for biofilm suppression effect. It was difficult to eliminate the risk of oral disease. In addition, in order to enhance these bactericidal powers, a technique for improving the retention of bactericides (Patent Document 2) has been proposed, but due to the low drug permeability of biofilms, a significant effect could not be expected. . From this current situation, there has been a strong demand for the development of a composition exhibiting an effective biofilm inhibitory action against bacteria in the biofilm.

  On the other hand, foam in dentifrice has a good feeling of use, improved ease of rinsing, improved dispersibility of the dentifrice composition, removal of dirt due to surface tension lowering action, enhancer function of active ingredients, etc. (non-patent literature) 6) It is an important function for a dentifrice composition. Among them, imparting good foam quality (fine foam) to the dentifrice composition is particularly important for improving the feeling of use.

  In recent years, as a biofilm inhibitory composition containing a dentifrice composition, a combination of a hydrophobic amino acid and an ammonium salt (Patent Document 3), a composition of a control substance for an inter-bacterial information transmission mechanism of plaque-constituting microorganisms (Patent Document 4), a lactone And / or furan derivative (Patent Document 5), glycerol phosphate and phenolic fungicide (Patent Document 6), nonionic antibacterial and dicarboxylic acid compound (Patent Document 7), ofloxacin and closantel Formulation of a phenolic fungicide (Patent Document 8) has been proposed, but it is difficult for these techniques to satisfy both foam quality and biofilm inhibitory activity which are important for dentifrice compositions. From such a current situation, development of a dentifrice composition having both good foam quality and oral biofilm inhibitory action as a substitute for the above technique is strongly desired.

  In addition, the biofilm inhibitory action is synergistically enhanced by the combination of polyoxyethylene hydrogenated castor oil having an average addition mole number of N, N-bis (2-octylaminoethyl) glycine and ethylene oxide of 80 to 100, and foam quality. Has never been reported to be good.

Costerton, J.M. W. , Stewart, P.M. S. and Greenberg, E.A. P. : Bacterial biofilms: a common cause of persistent influences. Science 284: 1318-1322, 1999. Costerton, J.M. W. Lewandowski, Z .; Caldwell, D .; E. Korber, D .; R. and Lappin-Scott, H .; M.M. : Microbiological biofilms. Annu. Rev. Microbiol. 49: 711-745, 1995. Hudson, M.M. C. Curtiss, R .; III: Regulation of expression of Streptococcus mutans genes important to virus. Infect. Immun. 58: 464-470, 1990. Stewart, P.M. S. : Mechanicals of antibiotic resistance in bacterial biofilms. Int. J. et al. Med. Microbiol. 292: 107-113, 2002. Philip Marsh and Michael V. Martin "Oral Microbiology", Wright Publishing, 2000, p. 58-81 (Dental plaque) Tajima Kazuo, Imai Yoko, Horiuchi Teruo: Application of Foam Fluoride Formulations to Oral Products-“Foam” Enhancer Effect on Exchangeability of Fluorine Ion and Hydroxyapatite Surfaces, Perspective of Dental Boundary Vol. 97 (5): 1125-1135, 2001. JP 02-11511 A JP 04-139119 A JP 2002-370953 A JP 2003-128580 A JP 2004-155681 A JP 2005-047855 A JP 2005-015369 A JP 2005-187377 A

  The present invention has been made to meet the above-described demands, and an object thereof is to provide a dentifrice composition having a high biofilm inhibitory action while having good foam quality.

  As a result of intensive research to achieve the above object, the present inventor has found that amphoteric surfactants such as alkyl polyaminoethyl glycine and polyoctyl polyaminoethyl glycine are subjected to high performance liquid chromatography, open column method, and thin layer chromatography. N, N-bis (2-octylaminoethyl) glycine or a salt thereof obtained by purification by a liquid-liquid extraction method or the like exhibits a high oral biofilm inhibitory effect, and this N, N-bis By blending (2-octylaminoethyl) glycine or a salt thereof and polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 80 to 100, both these components act synergistically. A remarkable oral biofilm inhibitory effect is exhibited, and an extremely good foam quality is imparted. It can be, therefore, to finding that a valid dentifrice compositions in the prevention and suppression of various oral diseases of periodontal disease and the like can be obtained, leading to completion of the present invention.

  Alkylpolyaminoethylglycine, as an amphoteric surfactant, has both a strong bactericidal power against airborne bacteria and a detergency, and it is known that there is little decrease in this bactericidal power even in the presence of protein. N, N-bis (2-octylaminoethyl) glycine or a salt thereof obtained by purifying this alkyl polyaminoethylglycine or polyoctylpolyaminoethylglycine has a high oral biofilm inhibitory effect, The inventor of the present invention has found for the first time that the oral biofilm inhibitory effect is synergistically improved and has a good foam quality by using oxyethylene cured castor in combination.

Accordingly, the present invention provides (A) N, N-bis (2-octylaminoethyl) glycine or a salt thereof in an amount of 0.04 to 0.3% by mass , and (B) an average addition mole number of ethylene oxide of 80 to A dentifrice composition comprising 0.1 to 2% by mass of 100 polyoxyethylene hydrogenated castor oil at a mass ratio of (A) / (B) of 1/5 to 1/50 The dentifrice composition further comprises dextranase.

  The dentifrice composition of the present invention has a remarkable oral biofilm inhibitory effect and extremely good foam quality, and is effective in preventing and suppressing various oral diseases.

  Hereinafter, the present invention will be described in more detail. The dentifrice composition of the present invention is a polyoxyethylene cured product having an average added mole number of N, N-bis (2-octylaminoethyl) glycine and ethylene oxide of 80 to 100. It is characterized by containing castor oil and more preferably dextranase.

  N, N-bis (2-octylaminoethyl) glycine blended in the composition of the present invention is represented by the following formula (1), which may be present as a salt such as hydrochloric acid or sodium.

  N, N-bis (2-octylaminoethyl) glycine of the above formula (1) is generally not commercially available as a pure product of N, N-bis (2-octylaminoethyl) glycine, but is commercially available. Alkyl polyaminoethylglycine, for example, products manufactured by Wako Pure Chemical Industries, Ltd. (reagents, etc.), products manufactured by Sanyo Kasei Kogyo Co., Ltd. (trade names: Levon 50, Levon U, etc.), products manufactured by Takemoto Yushi Co., Ltd. (trade names: Sarabon solution, Sarabon) 50 liquid, Sarabon L liquid, etc.) and commercially available polyoctyl polyaminoethylglycine, for example, a product (trade name: Obanol 516 etc.) manufactured by Toho Chemical Industry Co., Ltd. Aminoethyl) glycine can be obtained. Among these, commercially available alkyl polyaminoethyl glycine, particularly products manufactured by Wako Pure Chemical Industries, Ltd., and Sanyo Chemical Co., Ltd. due to the high content of N, N-bis (2-octylaminoethyl) glycine and the ease of isolation. It is preferable to obtain N, N-bis (2-octylaminoethyl) glycine using a product manufactured by Kogyo Co., Ltd.

Examples of the purification method for obtaining N, N-bis (2-octylaminoethyl) glycine of the above formula (1) include a high performance liquid chromatography method, an open column method, a thin layer chromatography method, and a liquid-liquid extraction method. However, the high performance liquid chromatography method is particularly suitable, and the purification conditions are not particularly limited, and can be carried out by a conventional method.
Among these, as a combination of a starting material and a purification method for obtaining N, N-bis (2-octylaminoethyl) glycine, impurities having an adverse effect on the effects of the present invention are efficiently excluded and high purity is obtained. N, N-bis (2-octylaminoethyl) glycine can be obtained, so that N, N-bis (2-octylaminoethyl) glycine can be obtained from commercially available alkylpolyaminoethylglycine by high performance liquid chromatography. Is preferred.

  In the present invention, N, N-bis (2-octylaminoethyl) glycine obtained by the above purification can be blended, but N, N-bis (2-octylaminoethyl) glycine is used instead of this pure product. An alkylpolyaminoethylglycine represented by the following general formula (2) or a salt thereof containing

（上記式中、Ｒ₁はＲ［ＮＨＣ₂Ｈ₄］_nで示される基、Ｒ₂はＲＮＨＣ₂Ｈ₄又は水素原子であり、Ｒは炭素数６〜１０のアルキル基、例えばＣ₆Ｈ₁₃，Ｃ₇Ｈ₁₅，Ｃ₈Ｈ₁₇，Ｃ₉Ｈ₁₉，Ｃ₁₀Ｈ₂₁であり、ｎは１又は２である。）

(In the above formula, R ₁ is a group represented by R [NHC ₂ H ₄ ] _n , R ₂ is RNHC ₂ H ₄ or a hydrogen atom, and R is an alkyl group having 6 to 10 carbon atoms, such as C ₆ H _13. , C ₇ H ₁₅ , C ₈ H ₁₇ , C ₉ H ₁₉ , C ₁₀ H ₂₁ , and n is 1 or 2.)

  As the alkylpolyaminoethylglycine of the above general formula (2) or a salt thereof containing such N, N-bis (2-octylaminoethyl) glycine, the above-mentioned commercially available alkylpolyaminoethylglycine or a salt thereof is used. Can be used.

In the present invention, N, N-bis amount of (2-octyl aminoethyl) glycine, N, N-bis 0.04 to 0.3 percent of the total composition as (2-octyl aminoethyl) glycine (mass %, The same shall apply hereinafter) . Not sufficient biofilm inhibiting effect is not obtained if the amount is less than 0.02%, that Do a problem in the formulation in terms of more than 1%, the foam quality and palatability.

  When N, N-bis (2-octylaminoethyl) glycine is blended with the above-mentioned alkylpolyaminoethylglycine of the general formula (2) or a salt thereof, from the viewpoint of influence on foam quality or supply ability N, N-bis (2-octylaminoethyl) glycine content is preferably 10% or more and less than 100%, more preferably 50% or more and less than 100%, and it is preferable to use alkylpolyaminoethylglycine or a salt thereof. It is preferable to blend such an alkylpolyaminoethylglycine or a salt thereof so that the content of N, N-bis (2-octylaminoethyl) glycine in the composition falls within the above range.

  In the polyoxyethylene hydrogenated castor oil in the present invention, it is essential that the average added mole number of ethylene oxide is 80 to 100, and more preferably 100 in terms of biofilm suppressing activity and foam quality. When the average number of added moles of ethylene oxide in the polyoxyethylene hydrogenated castor oil is less than 80, foam quality and biofilm suppression activity may be deteriorated, and those exceeding 100 are generally not commercially available.

The amount of the polyoxyethylene hydrogenated castor oil, 0.1% to 2% of the total composition, more preferably from 0.5% to 2%. The amount can not be obtained and satisfactory foam quality in the case of less than 0.1%, more than 5%, the biofilm inhibiting activity, foam quality, a negative impact on the palatability.

In the present invention, the blending ratio of N, N-bis (2-octylaminoethyl) glycine and polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 80 to 100 is the biofilm inhibiting effect and foam quality. From the surface, the mass ratio is 1: 5 to 1:50. When the mass ratio is outside the above range, sufficient biofilm inhibiting effect and satisfactory foam quality is that not obtained.

  In the present invention, dextranase is preferably further blended, and the biofilm inhibitory activity can be significantly increased by blending dextranase.

  Examples of the dextranase include dextranases obtained by known methods using known dextranase-producing bacteria belonging to the genus Ketomium, Penicillium, Aspergillus, Spicaria, Lactobacillus, Servibrio, etc. Dextranase produced by other microorganisms can also be used.

  Dextranase is 5 to 100 units per gram of composition (where 1 unit is the amount of enzyme that produces free reducing sugar corresponding to 1 μmol of glucose per minute when dextran is used as a substrate). The blending amount is preferably 0.05 to 1%, more preferably 0.05 to 0.5%, still more preferably 0 in the composition when, for example, 10,000 units / g dextranase is used. 0.1-0.3%. If the blending amount is less than 0.05%, a satisfactory biofilm inhibitory effect may not be obtained. If it exceeds 1%, the foam quality is adversely affected or the enhancement of the biofilm inhibitory effect is not recognized and economical. May be disadvantageous.

  The dentifrice composition of the present invention can be solid, solid, liquid, liquid, gel, paste, and can be prepared in various dosage forms such as toothpaste, liquid toothpaste, liquid toothpaste, and moisturized toothpaste. In particular, it can be suitably prepared as a liquid dentifrice or liquid dentifrice. The production 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-mentioned components, further appropriate optional components such as abrasives, surfactants, etc. Agents, binders, thickeners, fragrances, active ingredients and the like can be blended.

  For example, as a polishing agent, dicalcium phosphate dihydrate and anhydride, primary calcium phosphate, tertiary calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, anhydrous silicic acid, aluminum silicate, insoluble metaphosphoric acid One or more of sodium, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite, zirconium silicate, synthetic resin, etc. can be blended (mixing amount is usually 5 to 90%, toothpaste In the case of 10 to 60%).

  Moreover, 1 type (s) or 2 or more types of nonionic surfactants other than the said polyoxyethylene hydrogenated castor oil, and zwitterionic surfactant can be mix | blended as surfactant. Examples of anionic surfactants include sodium N-lauroyl sarcosinate, sodium N-acyl sarcosinate such as sodium N-myristoyl sarcosinate, hydrogenated coconut fatty acid monoglyceride sodium monosulfate, sodium lauryl sulfoacetate, sodium N-palmitoyl glutamate N-acyl glutamate such as sodium N-methyl-N-acyl taurate, sodium N-methyl-N-acylalanine, sodium α-olefin sulfonate and the like. 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 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 ethers, Polyoxyethylene polyoxypropylene copolymer, polyoxyethylene polyoxypropylene fatty acid ester, etc. are used. That. As the zwitterionic surfactant, N-alkyl-N-carboxymethylammonium betaine, sodium 2-alkyl-1-hydroxyethylimidazoline betaine and the like are used (the amount is usually 0.1 to 20.0%).

  As a binder, cellulose derivatives such as carrageenan, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl hydroxyethyl cellulose, alginates, propylene glycol alginate, xanthan gum, tragacanth gum, caraya gum, gum arabic gum, polyvinyl alcohol, One kind or two or more kinds of synthetic binders such as sodium polyacrylate, carboxyvinyl polymer, and polyvinylpyrrolidone, and inorganic binders such as silica gel, aluminum silica gel, bee gum, and laponite can be blended (the blending amount is usually 0.1. 3-10%).

  As a thickener, one or more of glycerin, ethylene glycol, diethylene glycol, hexylene glycol, butylene glycol, pentanediol, propylene glycol, sorbit, polyethylene glycol 200-20000, polypropylene glycol 300-4000, etc. are blended. To obtain (the amount is usually 1 to 70%).

  Perfumes include peppermint oil, spearmint oil, anise oil, eucalyptus 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, camomile oil, caraway oil, marjoram oil, lemongrass oil, origanum oil, pine needle oil, neroli oil, rose oil, jasmine oil, iris concrete, absolute peppermint, absolute rose, orange flower Natural fragrances, etc., and natural fragrances processed by these natural fragrances (front reservoir cut, rear reservoir cut, fractional distillation, liquid-liquid extraction, essence, powder fragrance, etc.), and menthol, carvone, anethole, cineole , Methyl salicylate, cinnamic aldehyde Eugenol, 3-l-menthoxypropane-1,2-diol, thymol, linalool, linalyl acetate, limonene, menthone, menthyl acetate, N-substituted-paramentane-3-carboxamide, pinene, octylaldehyde, citral, pregon, Carbyl acetate, anisaldehyde, ethyl acetate, ethyl butyrate, allyl cyclohexane propionate, methyl anthranilate, ethyl methyl phenyl glycidate, vanillin, undecalactone, hexanal, isoamyl alcohol, hexenol, dimethyl sulfide, cycloten, furfural , Trimethylpyrazine, ethyl lactate, ethyl thioacetate and other single flavors, strawberry flavor, apple flavor, banana flavor Examples of known fragrance materials used in oral compositions, such as blended fragrances such as flavors, pineapple flavors, grape flavors, mango flavors, butter flavors, milk flavors, fruit mix flavors, and tropical fruit flavors, can be used. It is not limited to fragrances. Although content is not specifically limited, It is preferable to use said fragrance | flavor raw material 0.000001 to 1% in a formulation composition. Moreover, as a fragrance | flavor for perfume which used the said fragrance | flavor raw material together, it is preferable to use 0.1 to 2.0% in a formulation composition.

  In the present invention, in addition to N, N-bis (2-octylaminoethyl) glycine or a salt thereof, other active ingredients such as chlorhexidine, benzethonium chloride, benzalkonium chloride, decalinium chloride and the like Ionic fungicides, phenolic compounds such as triclosan and hinokitiol, enzymes such as lysozyme, amylase and protease, alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, sodium fluoride, fluoride first Fluorides such as tin, tranexamic acid, epsilon aminocaproic acid, aluminum chlorohydroxyl allantoin, dihydrocholestanol, glycyrrhizic acids, glycyrrhetinic acid, bisabolol, glycerophosphate, chloro Phil, sodium chloride, water-soluble inorganic phosphoric acid compounds may be formulated alone or in combination. The blending amount of the other active ingredients can be an effective amount within a range not impeding the effects of the present invention (blending amount is usually 0.0001 to 5%).

  EXAMPLES Hereinafter, although an experimental example, an Example, and a comparative 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%.

[Experimental example]
A liquid dentifrice composition having the composition shown in Table 1 was prepared by the following method, and biofilm inhibitory activity and foam quality were evaluated by the following method. The results are shown in Table 1.

<Method for preparing liquid dentifrice compositions of Comparative Examples and Examples>
Weigh polyoxyethylene hydrogenated castor oil and polyoxyethylene lauryl ether, 50% aqueous solution of alkylpolyaminoethyl glycine hydrochloride, N, N-bis (2-octylaminoethyl) glycine and other components dissolved by heating at 60 ° C. After mixing and dispersing in 50 mL of distilled water at 40 ° C., the dextranase added group was mixed with dextranase and then diluted with distilled water so that the total amount was 100 mL.

  As will be described later, in Comparative Examples and Examples, as N, N-bis (2-octylaminoethyl) glycine, a commercially available alkylpolyaminoethylglycine hydrochloride aqueous solution or a commercially available alkylpolyaminoethylglycine hydrochloride aqueous solution was used. N, N-bis (2-octylaminoethyl) glycine isolated by a liquid chromatography method was used. Moreover, what was generally marketed was used for other components, such as polyoxyethylene hydrogenated castor oil.

<Measurement of biofilm inhibitory activity>
Streptococcus mutans ATCC 25175 strain, Actinomyces naeslundii ATCC 51655 strain, Fusobacterium new cactus Futacium new cactus F. ) ATCC 10953 strain, Porphyromonas gingivalis ATCC 33277 strain 40 μL of the bacterial solution, each autoclaved at 121 ° C. for 15 minutes, 5 mg / L hemin (manufactured by Sigma Aldrich) and 1 mg / L vitamin K Todd Hewit Broth (Bect) including Koyo Pharmaceutical Co., Ltd. was added to n and Dickinson Co.) broth (THBHM ^* 1) 4mL, overnight anaerobically cultured at 37 ° C. (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% of hydrogen) was. Todd Hewitt broth (Becton and Dickinson) containing 1.26% sodium lactate (manufactured by Sigma-Aldrich) obtained by autoclaving 80 μL of a solution of Veilloella parvula ATCC 17745 strain which had been stored in the same manner at 121 ° C. for 15 minutes. The product was added to 4 mL of a culture solution (THBL ^{* 2} ) and cultured in the same manner. After culturing, 300 μL was collected from each of the four bacterial strains excluding Bayonella pervula, added to 30 mL of THBHM, and further cultured overnight. Similarly, 300 μL was collected from the bacterial solution of Bayonella pervula, added to 30 mL of THBL, and cultured overnight. After re-culture, each bacterial solution was centrifuged (10000 rpm, 10 min), and the supernatant was discarded. After each suspension (bacteria) was autoclaved at 121 ° C. for 15 minutes, a basal medium mucin culture solution (BMM ^{* 3} ) was added and resuspended. Inoculated to 1 × 10 ⁷ cells / mL and cultured overnight at 37 ° C. under anaerobic conditions (95 vol% nitrogen, 5 vol% carbon dioxide). Thereafter, BMM was supplied at a rate of 100 mL / h, and the culture solution was discharged at the same rate. The culture solution discharged from the culture tank was continuously supplied to another culture tank in which the liquid volume was kept at 300 mL. A hydroxyapatite disk (diameter 7 mm × height 3.5 mm) as an attachment carrier was attached to a turntable (rotated at about 80 rpm) in the culture tank, and a biofilm was formed on the surface.

The culture by the above method was carried out for 14 days, and the following drug treatment was carried out for the latter 7 days.
That is, once a day, the biofilm was taken out from the culture vessel, treated with the test compositions (Examples and Comparative Examples) for 3 minutes, washed, and then returned to the culture vessel. The same operation was performed seven times.

At the end of the culture, the biofilm was transferred to a test tube (diameter 13 mm × 100 mm) to which 4 mL of THBHM was added in order to evaluate the biofilm inhibitory effect of the test composition. Immediately after sonication (200 μA output for 10 seconds) and serial dilution (10-fold dilution in 6 steps), each bacterial solution was smeared on a blood agar plate medium ^{* 4} prepared by a conventional method. The plate medium was anaerobically cultured (80 vol% nitrogen, 10 vol% carbon dioxide, 10 vol% hydrogen) until colonies could be confirmed with the naked eye. After counting the number of colonies in each plate medium, the number of viable bacteria was calculated by a conventional method. The result was shown by the viable bacteria reduction rate obtained by the following formula.

^{* 1} Composition of THBHM: Expressed by mass in 1 liter.
Todd Hewitt Broth (Becton and Dickinson)
30g / L
Hemin (manufactured by Sigma Aldrich) 5mg / L
Vitamin K (Wako Pure Chemical Industries) 1mg / L
Distilled water remaining
(Measured up so that the total amount was 1 L.)
^{* 2} THBL composition: Expressed by mass in 1 liter.
Todd Hewitt Broth (Becton and Dickinson)
30g / L
60% sodium lactate aqueous solution (Sigma Aldrich) 21g / L
Distilled water remaining
(Measured up so that the total amount was 1 L.)
^{* 3} Composition of BMM: Expressed by mass in 1 liter.
Proteose peptone (Becton and Dickinson)
2g / L
Tryptone (Becton and Dickinson) 1g / L
East Extract (Becton and Dickinson)
1g / L
Mucin (Sigma Aldrich) 2.5g / L
Hemin (Sigma Aldrich) 1mg / L
Vitamin K (Wako Pure Chemical Industries, Ltd.) 0.2mg / L
KCl (Wako Pure Chemical Industries, Ltd.) 0.5g / L
Cysteine (Wako Pure Chemical Industries, Ltd.) 0.1g / L
Distilled water remaining
(Measured up so that the total amount was 1 L.)
^{* 4} Composition of blood agar plate medium: Expressed by mass in 1 liter.
Todd Hewitt Broth (Becton and Dickinson)
30g / L
Agar (Becton and Dickinson) 15g / L
Hemin (manufactured by Sigma Aldrich) 5mg / L
Vitamin K (Wako Pure Chemical Industries) 1mg / L
Distilled water remaining
(Measured up so that the total amount was 1 L.)

<Evaluation of foam quality>
10 mL of test compositions (Examples and Comparative Examples) were dropped into the oral cavity of 10 professional panelists, rinsed for 20 seconds, brushed, and foam quality was evaluated according to the following criteria. The results are shown in the following ratings based on the dentifrice composition of Comparative Example 1.

Rating criteria;
Compared with Comparative Example 1, the fine texture of the foam: 5 points Compared with Comparative Example 1, the fine texture of the foam: 4 points Compared with Comparative Example 1, neither can be said: 3 points Comparative Example Compared with 1, the texture of the foam is slightly rough: 2 points Compared with Comparative Example 1, the texture of the foam is rough: 1 point Rating;
◎: 4.5 points or more ○: 4.0 points or more and less than 4.5 points △: 2.5 points or more and less than 4.0 points ×: Less than 2.5 points

^a) ; 50% alkylpolyaminoethylglycine hydrochloride aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd., N, N-bis (2-octylaminoethyl) glycine content = 56.7%) was blended, and N, N in the table -It was set as the compounding quantity of bis (2-octylamino ethyl) glycine. For example, in the case of Example 1, 0.35% of the above 50% aqueous alkylpolyaminoethylglycine hydrochloride solution was blended, and the blending amount of N, N-bis (2-octylaminoethyl) glycine was 0.1%.

^b) ; The amount of N, N-bis (2-octylaminoethyl) glycine obtained by the following purification method.
Purification method of N, N-bis (2-octylaminoethyl) glycine:
0.2 g of 50% aqueous solution of alkylpolyaminoethylglycine hydrochloride ^a) (manufactured by Wako Pure Chemical Industries, Ltd.) was weighed and diluted with distilled water so that the total amount became 100 mL. The aqueous solution was fractionated under the following conditions using high performance liquid chromatography (D-7000 type) manufactured by Hitachi, and a main peak with an elution time of about 20.8 minutes was collected (elution time: 20.6 to 21.2 minutes). Between). The collected eluate was freeze-dried (Tokyo Science Machinery Co., Ltd., FD-81) to obtain crystals (N, N-bis (2-octylaminoethyl) glycine). Since the molecular weight of the crystal was 385.6 (by mass spectrometer JMS manufactured by JEOL Ltd.), it was identified as N, N-bis (2-octylaminoethyl) glycine.

Conditions for high performance liquid chromatography Detector: UV 210 nm, flow rate: 1.0 mL / min,
Injection volume: 100 μL,
Column: Inert Sil ODS-3 (diameter: 4.6 × 150 mm) manufactured by GL Sciences Inc.
), Guard column: GL Sciences Inertsil ODS-3 (diameter 4.0 ×
10 mm),
Column temperature: 40 ° C
Mobile phase:
Within 5 minutes from the start of the analysis (elution time from 0 minutes to 5 minutes);
0.1% trifluoroacetic acid (manufactured by Wako Pure Chemical Industries, Ltd.) aqueous solution containing 5% acetonitrile (manufactured by Wako Pure Chemical Industries, Ltd.) over 5 minutes to 35 minutes from the start of analysis;
Acetonitrile concentration of 0.1% trifluoroacetic acid aqueous solution over time from 5% to 80%
(Linear gradient, for example, 20% after starting analysis, 0.1% trifluoroacetic acid containing 42.5% acetonitrile)
From 35 minutes to 40 minutes after the start of analysis;
0.1% aqueous trifluoroacetic acid solution containing 80% acetonitrile

^c) ; all manufactured by Nippon Surfactant Co., Ltd., POE number represents the average number of moles of ethylene oxide added to polyoxyethylene hydrogenated castor oil
^d) ; Sankyosha (10000 units / g)
^e) ; SDS = sodium lauryl sulfate (manufactured by Wako Pure Chemical Industries, Ltd., as a control of polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 80 to 100)
^f) ; POE lauryl ether = polyoxyethylene lauryl ether having an average addition mole number of ethylene oxide of 21 (manufactured by Nippon Surfactant, as a control of polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 80 to 100)
^g) ; CPC = cetylpyridinium chloride (manufactured by Wako Pure Chemical Industries, Ltd., as a control of N, N-bis (2-octylaminoethyl) glycine)

  From the above results, N, N-bis (2-octylaminoethyl) glycine or Comparative Examples 1, 2, N, N-bis (2-octylaminoethyl) glycine blended solely with polyoxyethylene hydrogenated castor oil and oxidation Comparative Examples 3 to 6 in combination with a surfactant other than polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene of 80 to 100, polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 100 and the conventional In Comparative Example 7 in combination with a bactericidal agent, results that satisfy both the biofilm inhibitory activity and foam quality were not obtained, but the average addition of N, N-bis (2-octylaminoethyl) glycine and ethylene oxide When polyoxyethylene hydrogenated castor oil having a mole number of 80 to 100 is used in combination (Example), a synergistic effect is exhibited, and in any evaluation Also good results, the effectiveness of the present invention was observed. In addition, when N, N-bis (2-octylaminoethyl) glycine purified product and alkylpolyaminoethylglycine hydrochloride have the same N, N-bis (2-octylaminoethyl) glycine concentration, equivalent biofilm inhibitory activity It was confirmed that foam quality was obtained.

  In the present invention, N, N-bis (2-octylaminoethyl) glycine and polyoxyethylene hydrogenated castor oil having an average added mole number of ethylene oxide of 80 to 100 are used in combination. 2-octylaminoethyl) glycine and / or ethylene oxide is considered to exhibit these effects by changing the properties of micelles of polyoxyethylene hydrogenated castor oil having an average added mole number of 80 to 100.

  Further, when N, N-bis (2-octylaminoethyl) glycine and polyoxyethylene hydrogenated castor oil having an average addition mole number of ethylene oxide of 80 to 100 are blended, and dextranase is blended (Example 13). 14), it was found that the biofilm suppression effect is further enhanced.

Example 15 Liquid Dentifrice N, N-Bis (2-octylaminoethyl) glycine ^* 0.11%
Polyoxyethylene (80) hydrogenated castor oil (manufactured by Nippon Surfactant) 1.0
Glycerin 15.0
Ethanol 15.0
Saccharin sodium 0.01
Sodium benzoate 0.3
Fragrance A 1.0
Disodium phosphate 0.05
Potassium nitrate 1.0
Sodium inosinate 1.0
Triclosan 0.15
Purified water remaining
Total 100.0%
^* 50% alkylpolyaminoethylglycine hydrochloride aqueous solution (Wako Pure Chemical Industries, Ltd., N, N-bis (2-octylaminoethyl) glycine content = 56.7%) was blended in an amount of 0.4%.

Example 16 Liquid dentifrice N, N-bis (2-octylaminoethyl) glycine ^* 0.04%
Polyoxyethylene (100) hydrogenated castor oil (manufactured by Nippon Surfactant) 1.5
Dextranase (Sankyo Co., Ltd., 12000 units / g) 0.25
Glycerin 35.0
Propylene glycol 5.0
Sodium polyacrylate 0.5
Silicic anhydride 15.0
Saccharin sodium 0.3
Sodium benzoate 0.3
Triclosan 0.1
β-glycyrrhetinic acid 0.05
Fragrance B 0.5
Potassium nitrate 3.0
Tranexamic acid 0.1
Tryptophan 0.5
Purified water remaining
Total 100.0%
^* 50% alkyl polyaminoethylglycine hydrochloride aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd., N, N-bis (2-octylaminoethyl) glycine content = 56.7%) was mixed in 0.15%.

[Example 17] Liquid toothpaste N, N-bis (2-octylaminoethyl) glycine ^* 0.06%
Polyoxyethylene (100) hydrogenated castor oil (manufactured by Nippon Surfactant) 2.0
Silicic anhydride 18.0
Xanthan gum 0.2
Sodium polyacrylate 0.1
70% sorbite solution 35.0
Glycerin 17.0
Propylene glycol 5.0
Saccharin sodium 0.3
Fragrance C 0.8
Purified water remaining
Total 100.0%
^* 50% alkylpolyaminoethylglycine hydrochloride aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd., N, N-bis (2-octylaminoethyl) glycine content = 56.7%) was blended in an amount of 0.2%.

[Example 18] Toothpaste N, N-bis (2-octylaminoethyl) glycine ^* 0.26%
Polyoxyethylene (80) hydrogenated castor oil (manufactured by Nippon Surfactant) 1.5
Carboxymethylcellulose 2.0
Sodium polyacrylate 0.3
70% sorbite solution 20.0
Propylene glycol 4.0
Polyethylene glycol 4000 0.5
Calcium hydrogen phosphate dihydrate 35.0
Silicic anhydride 5.0
Saccharin sodium 0.15
Sodium monofluorophosphate 0.41
Fragrance D 1.1
Purified water remaining
Total 100.0%
^* 0.9% of 50% alkylpolyaminoethylglycine hydrochloride aqueous solution (manufactured by Wako Pure Chemical Industries, Ltd., N, N-bis (2-octylaminoethyl) glycine content = 56.7%) was blended.

The perfumes A to D are as shown in Table 2 below.

* Fruit mix flavor FM3000 (mixed fragrance)
Strawberry flavor 25
Apple flavor 15
Melon Flavor 17
Banana Flavor 10
Peach flavor 5
Orange oil 2.5
Raspberry flavor 2
Pineapple flavor 15
Grape flavor 1
Tropical fruit flavor 1.5
Milk flavor 1
Grapefruit oil 0.5
Lemon oil 0.5
Rose oil 0.2
Ethanol remaining
Total 100%

  As mentioned above, as a result of performing evaluation similar to Example 1 with respect to Examples 15-18, the result much better than a comparative example was obtained in any of a biofilm suppression effect and foam quality.

Claims (3)

(A) 0.04 to 0.3% by mass of N, N-bis (2-octylaminoethyl) glycine or a salt thereof, and (B) polyoxyethylene curing with an average added mole number of ethylene oxide of 80 to 100 A dentifrice composition comprising 0.1 to 2% by weight of castor oil in a mass ratio of (A) / (B) of 1/5 to 1/50 .   The dentifrice composition according to claim 1, further comprising dextranase. The dentifrice composition of Claim 1 or 2 prepared as a liquid or liquid dentifrice.