JP4950726B2 - Oral composition - Google Patents

Description

  The present invention relates to a composition for oral cavity that is excellent in preventing cavity and preventing periodontal disease.

  Caries have one aspect as an intraoral infection that leads to onset due to adhesion and establishment of pathogenic bacteria on the tooth surface. The colonization of oral bacteria begins with the adsorption of early-fixing bacteria such as Streptococcus oralis, Streptococcus sangais, Streptococcus gordonii, Actinomyces naeslandi, etc. on the enamel surface covered with a thin film of saliva (pellicles). . These early-fixing bacteria co-aggregate with each other as they grow, and start to form plaque. Next, with the maturation of the plaque, the microbial flora transitions from facultative anaerobes to obligate anaerobes, and obligate anaerobes represented by Fusobacterium nucleatum co-aggregate with early-fixing bacteria. And it is thought that periodontal disease related bacteria, such as Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevoterra intermedia, co-aggregate and settle on the Fusobacterium nucleatum. Furthermore, Takemoto et al. Suggested that Streptococcus mutans, Streptococcus sobrinus, etc., which are caries-associated bacteria, co-aggregate with Fusobacterium nucleatum, and thus have a similar colonization mechanism (Non-patent Document 1).

  Such co-aggregation is caused by lectin-receptor type interaction between bacteria, nonspecific electrostatic interaction, adhesion action due to adhesive polysaccharide synthesis, nonspecific hydrophobic interaction, and the like. The oral bacteria that form plaques are composed of oral flora, unlike intestinal bacteria and skin resident bacteria, and lectin-receptor-type interactions are particularly important for colonization of pathogenic bacteria on the tooth surface. It is thought to play a role. This lectin-receptor type interaction is a stereospecific interaction between adhesin, which is usually a bacterial surface-binding protein, and receptor structures on other bacterial surface layers, and many of them exhibit hydrocarbon-specific binding.

  The most common lectin of bacteria forming plaque is the lactose-sensitive adhesin, which specifically recognizes β-galactoside in lactose. Lactose-sensitive adhesins are present in a wide range of oral bacteria, including Actinomyces, Streptococcus, Porphyromonas, Prevotella, Fusobacterium, Hemophilis, Capnocytophaga, Vironella, Neisseria, Selenomonas (Non-Patent Document 2).

  In particular, Fusobacterium bacteria express a large number of lactose-sensitive adhesins related to coaggregation. Early colonized bacteria adsorbed on the pellicle and Streptococcus sobrinus, caries-causing bacteria, and estimated periodontal diseases such as Porphyromonas gingivalis and Prevoterra intermedia. It is regarded as important as a bacterium that "bridges" related bacteria (Non-patent Document 2).

  As a means of preventing oral infection, it is considered to be effective to inhibit the colonization of pathogenic bacteria on the tooth surface. For example, galactose or lactose is used to suppress dental plaque adhesion. (Patent Document 1), use of a fatty acid sugar ester in which at least one fatty acid having 10 to 16 carbon atoms having antibacterial properties and fructose or galactose are ester-bonded (Patent Document 2) have been reported.

Furthermore, as a method for eliminating Fusobacterium nucleatum from the oral cavity, utilization of a specific antibacterial substance against the bacterium such as 3-methyl-5-phenyl-1-pentanol (Patent Document 3), anti-fusobacterium nucleatum capsular egg yolk antibody (Patent Document 4) has been proposed.
Japanese Patent Publication No.58-11924 JP 2000-159675 A Japanese Patent Laid-Open No. 9-110662 JP-A-10-152425 Journal of Periodontal Research, Vol. 30, p252-257 Infection and Immunity, Vol. 57, p3194-3203

The galactose and lactose described in Patent Document 1 are not preferable in terms of generating an acid that causes caries due to oral bacteria in the mouth, and the fatty acid sugar ester described in Patent Document 2 is also a component of the oral composition and the oral cavity. When hydrolyzed in the inside, fructose and galactose are produced, which causes similar problems. What is mentioned as an antibacterial agent specific to Fusobacterium nucleatum described in Patent Document 3 is a fragrance component, and the palatability of the oral composition is reduced due to a unique flavor, and the egg yolk antibody described in Patent Document 4 Has a problem that it is difficult to act on Fusobacterium bacteria in the biofilm due to the high molecular weight IgY antibody.
Accordingly, the present invention has a potent coaggregation-inhibiting action against caries-causing bacteria and periodontal disease-related bacteria of Fusobacterium, and specifically sterilizes Fusobacterium bacteria to prevent plaque formation. To provide things.

  Therefore, the present inventor examined the coaggregation inhibitory effect of Fusobacterium genus bacteria and caries-causing bacteria or periodontal pathogens with respect to various components. As a result, the compound represented by the formula (A) or (C) was obtained. It was found to have a strong coaggregation inhibitory action. Further examination revealed that the compound represented by the formula (A) or (C) has a completely unexpected effect that the bactericidal effect of the nonionic fungicide against Fusobacterium is significantly increased. It has been found that, if formulated, Fusobacterium spp. Bacteria can be sterilized strongly, and an oral composition useful for preventing caries and periodontal disease can be obtained.

  The present invention relates to the formula (A)

(In the formula, R represents an optionally substituted linear or branched alkyl group having 6 to 16 carbon atoms, G represents a galactose residue, E represents a hydrogen atom or a methyl group, and m represents 0. The present invention provides an oral composition containing a compound represented by ˜200 and n represents an integer of 1 to 30) and a nonionic fungicide.

  The present invention also provides a compound of formula (C)

(In the formula, R represents an optionally substituted linear or branched alkyl group having 6 to 16 carbon atoms, G represents a galactose residue, E represents a hydrogen atom or a methyl group, and x represents The number of 0-200 is shown, y shows the number of 1-30.) The composition for oral cavity containing the compound represented by the nonionic fungicide is provided.

When the composition of the present invention is used, co-aggregation of caries-causing bacteria such as Fusobacterium genus bacteria present in dental plaque and periodontal disease-related bacteria is suppressed, and Fusobacterium genus serving as a scaffold for the establishment of these pathogenic bacteria Since bacteria are sterilized, it becomes possible to prevent tooth decay and periodontal disease.
When the compound represented by the formula (A) or (C) and the nonionic fungicide are combined, the effect of enhancing the bactericidal effect against Fusobacterium is the common property of the compound represented by the formula (A) or (C). It cannot be explained only by the aggregation-inhibiting action and the bactericidal action of the nonionic fungicide. This is because when galactose or lactose having a coaggregation inhibitory action is combined with a nonionic fungicide, the bactericidal effect on Fusobacterium is not enhanced. Therefore, it is considered to be a unique effect when the compound represented by the above formula (A) or (C) and the nonionic fungicide are combined.

The compound represented by the formula (A) used in the present invention has one or more galactose residues directly or via one or more oxyethylene groups or oxypropylene groups to an alkyl group having 6 to 16 carbon atoms. It is a compound ether-bonded in the α-configuration or β-configuration. The alkyl group may be either linear or branched, specifically n-hexyl group; n-heptyl group, 1,4-dimethylpentyl group, 3-methylhexyl group, 4-methylhexyl group, Various heptyl groups such as 5-methylhexyl group; n-octyl group, 1,1,2-trimethylpentyl group, 1,1,4-trimethylpentyl group, 2,2-dimethylhexyl group, 1-methylheptyl group, Various octyl groups such as 5-methylheptyl group and 2-ethylhexyl group; various nonyl groups such as n-nonyl group, 1-methyloctyl group, 6-methyloctyl group and 8-methyloctyl group; n-decyl group, 3 , 7-dimethyloctyl group, 1-methylnonyl group, 8-methylnonyl group and the like; n-undecyl group, 1-methyldecyl group, 2-methyldecyl group, 9-methyl Various undecyl groups such as decyl group; various dodecyl groups such as n-dodecyl group, 2-butyloctyl group, 1-methylundecyl group, 10-methylundecyl group; n-tridecyl group, 1-methyldodecyl group, 11 -Various tridecyl groups such as methyldodecyl group; Various tetradecyl groups such as n-tetradecyl group, 1-methyltridecyl group, 12-methyltridecyl group; n-pentadecyl group, 1-methyltetradecyl group, 13-methyltetra Examples include various pentadecyl groups such as a decyl group; various hexadecyl groups such as an n-hexadecyl group, a 2-hexyldecyl group, a 1-methylpentadecyl group, and a 14-methylpentadecyl group. Among these alkyl groups, from the aspects of flavor, retention in the oral cavity, and foaming properties, 8 to 14 carbon atoms are preferable, and in particular, linear or branched chains having 10 to 14 carbon atoms, or mixtures thereof are preferable. In the straight chain, a dodecyl group (lauryl group) alone alkyl group composition, or a mixed alkyl group composition consisting of decyl group, dodecyl group, and tetradecyl group is particularly preferred, and in branched chain, a 2-ethylhexyl group alone alkyl group composition or branched decyl group. As the mixed alkyl group composition composed of isomers and the mixture of straight and branched chains, a mixture of undecyl group and 2-methyldecyl group is particularly preferable. One or more hydrogen atoms of the alkyl group may be substituted with a substituent, and examples of the substituent include an alkoxy group having 1 to 6 carbon atoms and a halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.). ), A nitro group, a haloalkyl group having 1 to 6 carbon atoms, and a haloalkoxy group having 1 to 6 carbon atoms.
Moreover, the galactose of the compound represented by the formula (A) used in the present invention includes any of a pyranose type, a furanose type, or a mixture thereof. Although m shows the integer of 0-200, 0-12 are preferable and 0-3 are more preferable from the surface of a coaggregation inhibitory effect. Although n which shows the condensation degree of galactose is an integer of 1-30, 1-6 are preferable from the surface of foamability, and 1-3 are more preferable.

  In addition, the compound used in the present invention has the formula (B) in which E is a hydrogen atom in the formula (A).

(In the formula, R represents an optionally substituted linear or branched alkyl group having 6 to 16 carbon atoms, G represents a galactose residue, m represents an integer of 0 to 200, and n represents 1) The compound represented by the integer of ~ 30 is preferable.

Further, the compound used in the present invention may be a mixture containing two or more kinds of compounds. In formula (C) which is such a mixture, the alkyl group which may be substituted in R is an alkyl group having an average carbon number of 6 to 16, preferably from the aspects of flavor, retention in the oral cavity and foaming property. The average carbon number is 10-14. The average degree of polymerization x is a number from 0 to 200, preferably a number from 0 to 12, and more preferably a number from 0 to 3. The average degree of condensation y of galactose is a number of 1 to 30, but the number of 1 to 6 is preferable and the number of 1 to 3 is more preferable in terms of the coaggregation suppressing action. In addition, the average condensation degree y of galactose can be calculated based on the composition of the component of each condensation degree obtained from analytical methods such as gel permeation chromatography. For example, in the case of an alkyl galactoside mixture having a condensation degree of 1 to z of galactose, assuming that the molar ratio of the galactoside having a condensation degree z is a _z (a ₁ + a ₂ + a ₃ +... + A _z = 1), The average degree of condensation is represented by y = a ₁ × 1 + a ₂ × 2 +... + A _z × z = Σ (a _z × z).
Further, the average carbon number of the alkyl group represented by the average degree of polymerization x or R of the oxyethylene group or oxypropylene group can be calculated in the same manner.

  The compounds represented by the formulas (A) to (C) are galactose and alcohol described in Hori et al.'S method (Pharmaceutical Journal, Vol. 79, No. 1, p80-83) and Reference Examples 1 to 6 described later. It can be produced by the synthesis of

  The compounds represented by the formulas (A) to (C) strongly suppress co-aggregation of Fusobacterium genus bacteria that are resident bacteria and caries-causing bacteria. Here, examples of the genus Fusobacterium include Fusobacterium nucleatum and Fusobacterium rouge. Examples of caries-causing bacteria include Streptococcus mutans, Streptococcus sobrinus, and the like. Examples of periodontal disease-related bacteria include Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevoterra intermedia.

  0.05-20 mass% is preferable, as for content in the whole composition for oral cavity of this invention of the compound represented by Formula (A)-(C), More preferably, 0.1-10 mass%, More preferably, It is 0.2-5 mass%.

  Nonionic fungicides used in the present invention include phenolic fungicides, tropolone fungicides, and halogenated carbanilide fungicides. Examples of the phenolic fungicide include phenol, cresol, triclosan (5-chloro-2- [2,4-dichlorophenoxyl] phenol), isopropylmethylphenol (3-Methyl-4-isopropylphenol), and thymol (2-Isopropyl-5). -Methylphenol). Examples of the tropolone fungicide include β-tubulin (hinokitiol), β-drabrin, γ-tubulin, α-tubulin, and 4-acetyltropolone. Examples of the halogenated carbanilide fungicide include trichlorocarbanilide (3,4,4′-Trichlorocarbanilide). The content of these nonionic fungicides in the composition for oral cavity of the present invention is preferably 0.001 to 0.5% by mass, more preferably 0.005 to 0.2% by mass, and still more preferably 0.01 to 0.1% by mass.

  Further, according to the study of the present inventor, the sugar alcohol having 4 to 12 carbon atoms has an action of delaying the binding between the Fusobacterium genus bacteria and the caries-causing bacteria and does not produce an acid in the oral cavity. That is, by using these sugar alcohols in combination, the effect as the coaggregation inhibitor of the present invention can be improved. Therefore, the composition for oral cavity of the present invention preferably contains a sugar alcohol having 4 to 12 carbon atoms from the viewpoint of the coaggregation suppressing effect. Examples of the sugar alcohol having 4 to 12 carbon atoms include sorbitol, mannitol, xylitol, erythritol, palatinit, lactitol and the like. The content of the sugar alcohol having 4 to 12 carbon atoms in the entire composition for oral cavity of the present invention is preferably 4 to 60% by mass, and more preferably 10 to 50% by mass.

  The combined use of the compounds represented by formulas (A) to (C) and a sugar alcohol having 4 to 12 carbon atoms is also useful from the aspect of flavor. The sugar alcohol having 4 to 12 carbon atoms is preferably contained in an amount of 1 to 500 parts by mass with respect to 1 part by mass of the compounds (A) to (C), particularly 5 to 400 parts by mass for a toothpaste and a mouthwash. It is preferable to contain 10-200 mass parts.

  In addition to the above components, various components can be blended in the oral composition of the present invention depending on the form. Ingredients that can be added include, for example, wetting agents, binders, dentin enhancers, bactericides, pH adjusters, enzymes, anti-inflammatory agents, blood circulation promoters, sweeteners, preservatives, colorants, pigments, and fragrances Etc. can be used as appropriate. Moreover, unless the effect of this invention is impaired, surfactant other than the compound represented by Formula (A)-(C) can also be mix | blended.

  The composition for oral cavity of the present invention can be produced by a conventional method by blending the compounds represented by the formulas (A) to (C) and the nonionic fungicide and, if necessary, the sugar alcohol. , Liquid toothpaste, toothpaste, moisturized toothpaste, paste-like cleaning agents such as oral pasta, mouthwash, liquid cleaning agents such as mouthwash, gargle tablets, gum massage cream, chewing gum, troches, candy and other foods It can be in the form.

Reference Example 1 Production of α, β-lauryl galactoside D-galactose and lauryl alcohol were reacted in the presence of a catalytic amount of paratoluenesulfonic acid monohydrate while dehydrating under heating and reduced pressure conditions. The resulting mixture was purified by a silica gel column to obtain lauryl galactoside having a degree of galactose condensation of 1 to 3. As a result of analysis by gel permeation chromatography, gas chromatography and ¹ H-NMR, the average condensation degree of galactose of the obtained lauryl galactoside was 1.48, and the composition of lauryl monogalactoside in the component was pyranoside / furanoside = 83. / 17, of which the α / β ratio of pyranoside was 75/25. This was used as α, β-lauryl galactoside in Reference Examples and Examples described later.

Reference Example 2 Production of β-trioxyethylene lauryl galactoside Pentaacetyl-D-galactose and trioxyethylene monolauryl ether were reacted in dichloromethane in the presence of boron trifluoride diethyl ether complex at room temperature. After distilling off the solvent under reduced pressure, β-trioxyethylene lauryl-2,3,4,6-tetraacetylgalactoside was obtained by purification with a silica gel column. This was deacetylated with sodium methoxide to obtain β-trioxyethylene lauryl galactoside. ¹ H-NMR (400 MHz, CDCl ₃ ) 0.88 (t, 3H), 1.2-1.35 (m, 18H), 1.57 (m, 2H), 3.35-3.8 (overlapped) , 13H), 3.84 (t, 2H), 3.97-4.07 (overlapped, 3H), 4.17 (d, 1H), 4.29 (d, J = 7.6 Hz, 1H), 4.41 (d, 1H). This was used as β-trioxyethylene lauryl galactoside (degree of galactose condensation is 1) in Reference Examples and Examples described later.

Reference Example 3 Production of α- and β-octylgalactoside α, β-octylgalactoside produced using octyl alcohol as a raw material in the same manner as in Reference Example 1 was purified with a column to obtain α-octylgalactoside and β-octylgalactoside. α form: 0.78 (t, 3H), 1.1-1.3 (m, 10H), 1.47 (m, 2H), 3.45-3.70 (overlapped, 7H), 4.63 (D, J = 2.8 Hz, 1H), β-form: 0.86 (t, 3H), 1.2-1.35 (m, 10H), 1.51 (m, 2H), 3.25- 3.75 (overlapped, 7H), 4.09 (d, J = 7.6 Hz, 1H). These were used as α-octyl galactoside and β-octyl galactoside (the degree of galactose condensation was 1, respectively) in Reference Examples and Examples described later.

Reference Example 4 Production of α, β-2-ethylhexylgalactoside D-galactose and 2-ethylhexanol were reacted in the presence of a catalytic amount of paratoluenesulfonic acid monohydrate while dehydrating under heating and reduced pressure conditions. After the reaction, an aqueous sodium hydroxide solution was added to neutralize the catalyst, and unreacted D-galactose was removed from the resulting mixture by filtration. 2-ethylhexyl galactoside was obtained by distilling off the unreacted alcohol from the filtrate under reduced pressure. As a result of analysis by gel permeation chromatography, gas chromatography and ¹ HNMR, the average condensation degree of galactose of the obtained 2-ethylhexyl galactoside was 1.16, and the composition of monogalactoside in the composition was pyranoside / furanoside = 40. / 60, of which the α / β ratio of pyranoside was 70/30. This was used as 2-ethylhexyl galactoside in Reference Examples and Examples described later.

Reference Example 5 Production of α, β-decylgalactoside According to Reference Example 4, decylgalactoside was obtained according to Reference Example 4 except that 2-ethylhexanol of Reference Example 4 was changed to a decanol isomer mixture (decanol, Kyowa Hakko Chemical Co., Ltd.). The average degree of condensation of galactose of the obtained decylgalactoside was 1.15, and the composition of monogalactoside in the composition was pyranoside / furanoside = 46/54, of which the α / β ratio of pyranoside was 67/33. This was used as α, β-decylgalactoside in Reference Examples and Examples described later.

Reference Example 6 Production of α, β-undecylgalactoside According to Reference Example 4 except that 2-ethylhexanol of Reference Example 4 was changed to an undecanol isomer mixture (Diadol 11, Mitsubishi Chemical Co., Ltd.), Obtained. The average degree of condensation of galactose of the obtained undecylgalactoside was 1.16, and the composition of monogalactoside in the composition was pyranoside / furanoside = 52/48, of which the α / β ratio of pyranoside was 71/29 . This was used as α, β-undecylgalactoside in Reference Examples and Examples described later.

Reference Example 7 (Coaggregation inhibitory effect)
(1) Strain used As Fusobacterium spp., Fusobacterium nucleatum polymorphic ATCC 10953 (hereinafter referred to as Fnp), Fusobacterium nucleatum Fujiform JCM11024 (hereinafter referred to as Fnf), Fusobacterium periodonticum ATCC 33893 (hereinafter referred to as Fp), Fusobacterium valium ATCC8501 Bacteria), Fusobacterium maltiferum ATCC 25557 strain (hereinafter referred to as Fm). As bacteria against the coaggregation reaction, Streptococcus sobrinus B13 strain (hereinafter referred to as Ss) was used as a caries-causing bacterium, and Actinobacillus actinomycetemcomitans JCM2434 strain (hereinafter referred to as Aa) was used as a periodontal disease-related bacterium.

(2) Coaggregation measurement method Ss bacteria and Aa bacteria were cultured for 24 hours under anaerobic conditions at 37 ° C. after inoculation in a brain heart infusion liquid medium. Fusobacterium was inoculated in a GAM bouillon liquid medium and cultured for 48 hours under anaerobic conditions at 37 ° C. After completion of the culture, the cells are collected by centrifugation, and the solution is co-aggregated with pH 8.0 (1 mM tris (hydroxymethyl) aminomethane, 0.1 mM calcium chloride, 0.1 mM magnesium chloride, 0.15 M sodium chloride). Washed twice. After washing, Ss bacteria and Aa bacteria were reduced to 0.5 so that the turbidity at 600 nm wavelength (OD: UV-1600, UV-Visible spectrophotometer (Shimadzu Corporation)) was 1.0. A bacterial suspension was obtained by adjusting with a coaggregation buffer. Test substances such as the compound represented by the formula (A) were preliminarily adjusted with a co-aggregation buffer so that the amount of the test substance was 1.6% (wt / vol%). As comparative substances, lactose, galactose, sucrose, glucose, maltose (above, Wako Pure Chemical Industries, Ltd.), β-lauryl maltoside (Dojin Pharmaceutical Co., Ltd.), C10: C14 alkyl glucoside (Cognis Japan) were used. The co-aggregation test uses a round bottom 96-well microplate (TPP), and 100 μL of any Fusobacterium suspension, 50 μL of Ss or Aa suspension and 1.6% (wt / vol%) test substance 50 μL of the solution was mixed sequentially. In the control group to which the test substance was not added after standing at room temperature for a whole day and night, the coagulant ability (*) indicates that the agglomerate is produced, and the coagulation ability is not produced (x) if the aggregate is not produced. did. The presence or absence of coaggregation inhibitory activity was observed when a test substance was added to the combination in which the coaggregation activity was observed in the control group, and the coagulation inhibitory activity was observed for those in which no aggregate precipitation was observed (+). Was regarded as having no coaggregation inhibiting activity (−).

(3) Results As shown in Table 1, among the Fusobacterium species tested, Fnp fungus, Fnf fungus, and Fp fungus have coaggregation ability with Ss fungus and Aa fungus, and have a great influence on the establishment of pathogenic fungi There were thought to be Fusobacterium spp. Fv bacteria and Fm bacteria did not have coaggregation ability with respect to these bacteria, and it was considered that galactose-sensitive adhesins were not expressed.
Tables 2 to 4 show the results of the coaggregation inhibition test for Fusobacterium 3 strains in which the coaggregation ability of Fnp bacteria, Fnf bacteria, and Fp bacteria was recognized. In sucrose, glucose, maltose, C10: 14 alkyl glucoside, and β-lauryl maltoside, clear aggregates due to co-aggregation were observed, but α, β-lauryl galactoside, β-trioxyethylene lauryl galactoside, α-octyl galactoside Β-octyl galactoside, α, β-2-ethylhexyl galactoside, α, β-decyl galactoside, α, β-undecyl galactoside were found to have coaggregation-inhibiting activity like lactose and galactose.

Example 1 (Enhancement of bactericidal activity against Fusobacterium)
(1) Strain used The same strain as in Reference Example 4 was used.

(2) Culture and bactericidal activity test As the medium, GAM bouillon (Nissui Pharmaceutical Co., Ltd.) was used as the genus Fusobacterium, and Brain Heart Infusion Broth (Becton Dickinson) was used as the Ss and Aa bacteria. Bacteria cultured on Anero Columbia rabbit blood agar medium for 24 to 36 hours have turbidity at a wavelength of 600 nm in the above liquid medium under conditions of 37 ° C., 10% CO ₂ , 10% H ₂ , 80% N _2. After culturing to the late logarithmic growth phase so as to be about 0.5 to 1, the cells were collected by centrifugation at 5,000 rpm for 5 minutes. Then, after washing with pre-anaerobic physiological saline (Otsuka Pharmaceutical Co., Ltd.), the colony forming unit was diluted so as to be in the range of 1 × 10 ⁶ to 1 × 10 ⁸ CFU / mL.

  A liquid medium containing 0.4% (wt / vol%) of the test substance and nonionic disinfectant to a predetermined concentration is added to the liquid medium containing 0.4% (wt / vol%) of the test substance. The solution was diluted two times sequentially and dispensed in advance to a round-bottom 96-well plate in a volume of 0.2 mL. Thereafter, 0.02 mL of the bacterial suspension was added. The final concentration (ppm) having the lowest nonionic fungicide concentration in the wells in which the cells were cultured for 48 hours under the above-mentioned conditions and no growth of bacteria was observed was defined as the minimum growth inhibitory concentration (MIC).

  7 of α, β-lauryl galactoside, β-trioxyethylene lauryl galactoside, α-octyl galactoside, β-octyl galactoside, α, β-2-ethylhexyl galactoside, α, β-decyl galactoside, α, β-undecyl galactoside In the component, the effect of enhancing the bactericidal activity of triclosan selective to Fnp bacteria, Fnf bacteria and Fp bacteria having coaggregation ability was recognized. No effect of enhancing bactericidal activity was observed against Fusobacterium spp. Bacteria having no coaggregation ability such as Fv fungi and Fm fungi and bacteria having different genera such as Aa fungi. A compound having no ability to suppress coaggregation such as sucrose, glucose, maltose, C10: 14 alkyl glucoside, and β-lauryl maltoside did not show the bactericidal activity enhancing effect. A compound that does not contain a linear or branched alkyl group having 6 to 16 carbon atoms in its structure, such as galactose or lactose, has no ability to enhance bactericidal activity despite its ability to suppress coaggregation.

7 of α, β-lauryl galactoside, β-trioxyethylene lauryl galactoside, α-octyl galactoside, β-octyl galactoside, α, β-2-ethylhexyl galactoside, α, β-decyl galactoside, α, β-undecyl galactoside As the component, an effect of enhancing the bactericidal activity of isopropylmethylphenol selective to Fnp bacteria, Fnf bacteria and Fp bacteria having coaggregation ability was recognized. However, no effect of enhancing bactericidal activity was observed against Fusobacterium spp. Bacteria having no coaggregation ability such as Fv fungi and Fm fungi and bacteria having different genera such as Aa fungi. A compound having no ability to suppress coaggregation such as sucrose, glucose, maltose, C10: 14 alkyl glucoside, and β-lauryl maltoside did not show the bactericidal activity enhancing effect. A compound that does not contain a linear or branched alkyl group having 6 to 16 carbon atoms in its structure, such as galactose or lactose, has no ability to enhance bactericidal activity despite its ability to suppress coaggregation.
In addition, since the bactericide concentration set in the measurement of MIC this time is a 2-fold dilution series, a result in which the difference in MIC values is within 2 times is considered to be within the range of experimental error.

  7 of α, β-lauryl galactoside, β-trioxyethylene lauryl galactoside, α-octyl galactoside, β-octyl galactoside, α, β-2-ethylhexyl galactoside, α, β-decyl galactoside, α, β-undecyl galactoside In the component, the effect of enhancing the bactericidal activity of hinokitiol selective against Fnp bacteria, Fnf bacteria and Fp bacteria having coaggregation ability was recognized. However, no effect of enhancing bactericidal activity was observed against Fusobacterium spp. Bacteria having no coaggregation ability such as Fv fungi and Fm fungi and bacteria having different genera such as Aa fungi. A compound having no ability to suppress coaggregation such as sucrose, glucose, maltose, C10: 14 alkyl glucoside, and β-lauryl maltoside did not show the bactericidal activity enhancing effect. A compound that does not contain a linear or branched alkyl group having 6 to 16 carbon atoms in its structure, such as galactose or lactose, has no ability to enhance bactericidal activity despite its ability to suppress coaggregation.

(3) Results α, β-lauryl galactoside, β-trioxyethylene lauryl galactoside, α-octyl galactoside, β-octyl galactoside, α, β-2-ethylhexyl galactoside, α, β-decyl galactoside, α, β-un The MIC of decylgalactoside for each bacterium was 4000 ppm (0.4% (wt / vol%)), and the bactericidal ability was extremely low. The MIC of triclosan for each bacterium was 0.5 to 8 ppm, hinokitiol was 8 to 32 ppm, and isopropylmethylphenol (using 3-methyl-4-isopropylphenol) was 256 to 512 ppm. Since the concentration of the bactericide set in the measurement of MIC this time is a 2-fold dilution series, a result in which the difference in MIC values is within 2 times is considered to be within the range of experimental error. To this, 0.1% (wt / vol%) α, β-lauryl galactoside, β-trioxyethylene lauryl galactoside, α-octyl galactoside, β-octyl galactoside, α, β-2-ethylhexyl galactoside, α, When β-decylgalactoside or α, β-undecylgalactoside is added, the MIC for Fnp bacteria, Fnf bacteria, and Fp bacteria is 1/4 to 1/16, and these galactose derivatives are sterilized by nonionic fungicides. The effect was remarkably enhanced. However, the MIC did not change and did not enhance the bactericidal effect against Fv bacteria, Fm bacteria, Ss bacteria, and Aa bacteria that do not have coaggregation ability, that is, no galactose-sensitive adhesin, and bacteria other than the genus Fusobacterium. That is, it was shown that the combination of a galactose derivative and a nonionic fungicide in the present invention can selectively kill bacteria belonging to the genus Fusobacterium having coaggregation ability.
On the other hand, the bactericidal activity enhancing effect was not observed for compounds such as sucrose, glucose, maltose, C10: 14 alkyl glucoside, and β-lauryl maltoside that did not have the ability to suppress coaggregation. In addition, a combination of a compound containing no linear or branched alkyl group having 6 to 16 carbon atoms in the structure and a nonionic fungicide, despite the ability to suppress coaggregation such as galactose and lactose, No enhancement of the bactericidal effect was observed.

Example 2
The prescription of the toothpaste of the present invention is as follows.
Sorbitol 35% by mass
Silica anhydride 20% by mass
Concentrated glycerin 5% by mass
α, β-lauryl galactoside 5% by mass
Sodium carboxymethyl cellulose 1% by mass
Toothpaste fragrance 1% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Triclosan 0.03% by mass
Purified water balance
100% by mass in total

Example 3
The prescription of the toothpaste of the present invention is as follows.
Sorbitol 28% by mass
Silica anhydride 20% by mass
Concentrated glycerin 8% by mass
Erythritol 5% by mass
Sodium lauryl sulfate 1.2% by mass
Sodium carboxymethyl cellulose 1% by mass
Toothpaste fragrance 1% by mass
α, β-lauryl galactoside 0.5% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Isopropyl methylphenol 0.1% by mass
Purified water balance
100% by mass in total

Example 4
The prescription of the toothpaste of the present invention is as follows.
Sorbitol 25% by mass
Silica anhydride 20% by mass
Propylene glycol 6% by mass
Lactitol 5% by mass
Sodium lauryl sulfate 1.2% by weight
Sodium carboxymethyl cellulose 1% by mass
Toothpaste fragrance 1% by mass
α, β-2-ethylhexyl galactoside 0.5% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Hinokitiol 0.1% by mass
Purified water balance
100% by mass in total

Example 5
The prescription of the toothpaste of the present invention is as follows.
Sorbitol 28% by mass
Polyoxyethylene (200) polyoxypropylene (40) copolymer 16% by mass
Silica anhydride 12% by mass
Palatinit 10% by mass
Concentrated glycerin 8% by mass
Sodium lauryl sulfate 1.2% by mass
Sodium carboxymethylcellulose 1.5% by mass
Toothpaste fragrance 1% by mass
α, β-undecylgalactoside 0.8 mass%
Sodium monofluorophosphate 0.7% by mass
Saccharin sodium 0.2% by mass
Triclosan 0.03% by mass
Purified water balance
100% by mass in total

Example 6
The prescription of the toothpaste of the present invention is as follows.
Sorbitol 28% by mass
Silica anhydride 15% by mass
Polyethylene glycol 400 8% by mass
Xylitol 5% by mass
Sodium lauryl sulfate 1.2% by mass
Sodium carboxymethyl cellulose 1% by mass
Toothpaste fragrance 1% by mass
α, β-decylgalactoside 0.1% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Isopropyl methylphenol 0.1% by mass
Purified water balance
100% by mass in total

Example 7
The prescription of the mouthwash of the present invention is as follows.
Ethanol 15 mass%
Xylitol 7% by mass
Polyoxyethylene hydrogenated castor oil 2% by mass
Saccharin sodium 0.5% by mass
β-octylgalactoside 0.2% by mass
Fragrance for mouthwash 0.2% by mass
Sodium benzoate 0.1% by mass
Triclosan 0.02% by mass
Purified water balance
100% by mass in total

Claims (3)

Formula (A)

(In the formula, R represents an optionally substituted linear or branched alkyl group having 6 to 16 carbon atoms, G represents a galactose residue, E represents a hydrogen atom or a methyl group, and m represents 0. An integer of ˜200, n represents an integer of 1 to 30) , and
An oral composition containing a nonionic fungicide selected from phenol, cresol, triclosan, isopropylmethylphenol, thymol, hinokitiol, β-drabrin, γ-tubulin, α-tubulin and 4-acetyltropolone . Formula (C)

(In the formula, R represents an optionally substituted linear or branched alkyl group having 6 to 16 carbon atoms, G represents a galactose residue, E represents a hydrogen atom or a methyl group, and x represents A number of 0 to 200, y is a number of 1 to 30) , and
An oral composition containing a nonionic fungicide selected from phenol, cresol, triclosan, isopropylmethylphenol, thymol, hinokitiol, β-drabrin, γ-tubulin, α-tubulin and 4-acetyltropolone . Furthermore, the composition for oral cavity of Claim 1 or 2 containing C4-C12 sugar alcohol.