JP4820320B2 - Oral composition - Google Patents

Description

  The present invention relates to an oral cavity composition that is excellent in caries prevention effect and periodontal disease prevention effect and is stable.

  Caries have one aspect as an intraoral infection that leads to onset due to adhesion and establishment of pathogenic bacteria on the tooth surface. First of all, the colonization mechanism of oral bacteria on the tooth surface is adsorbed by the initial colonization 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 coaggregation is caused by lectin / receptor type interaction between bacteria, nonspecific electrostatic interaction, adhesion by sticky polysaccharide synthesis, and nonspecific hydrophobic interaction. 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.
Japanese Patent Publication No.58-11924 JP 2000-159675 A Journal of Periodontal Research, Vol. 30, p252-257 Infection and Immunity, Vol. 57, p3194-3203

As a result of studies to solve this problem, alkyl galactoside, in which an alkyl group is ether-bonded to galactose, has an excellent inhibitory action on co-aggregation of Fusobacterium bacteria with caries-causing bacteria or periodontal disease-causing bacteria. It was found useful as a composition for oral cavity for preventing cavity and periodontal disease. However, this alkyl galactoside may also be decomposed under high temperature conditions, and it has been found that a long-term stable formulation design is required without being affected by storage conditions.
Accordingly, an object of the present invention is to provide an oral composition containing an alkyl galactoside and having good stability.

  Then, when this inventor examined the stable compounding property of the alkyl galactoside, if the pH was adjusted to 5.5-9, it discovered that it did not decompose | disassemble even if it preserve | saves for a long period of time on high temperature conditions. Furthermore, it has also been found that an alkyl galactoside-containing composition adjusted to pH 5.5-9 significantly reduces the irritation to the oral mucosa of an anionic surfactant widely blended in oral products. Furthermore, it has also been found that in a system in which an alkyl galactoside and an anionic surfactant are used in combination, the ability to solubilize menthol is improved, menthol crystals are not precipitated, and an oral composition having a refreshing feeling 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 composition for oral cavity which contains the compound represented by the integer represented by -200, n shows the integer of 1-30, and is pH 5.5-9 is provided.

  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 It shows the number of 0-200, y shows the number of 1-30.) The compound represented by this is provided, and the composition for oral cavity which is pH 5.5-9 is provided.

  Furthermore, this invention provides the said composition for oral cavity containing an anionic surfactant, and the said composition for oral cavity containing an anionic surfactant and menthol.

  The composition for oral cavity of this invention is excellent in the coaggregation inhibitory effect with respect to the caries causative bacteria and periodontal disease related bacteria, such as a Fusobacterium genus bacteria which exists in dental plaque, and is excellent in long-term storage stability. Moreover, even if it mix | blends an anionic surfactant, the irritation | stimulation to an oral mucosa is reduced.

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 a number of 1 to 10 is preferable and a number of 1 to 3 is more preferable in terms of the coaggregation suppressing action. The average degree of condensation y of galactose can be calculated based on the composition ratio of the components of each degree of condensation 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.

  The content of the compounds represented by the formulas (A) to (C) in the whole oral cavity composition of the present invention is preferably 0.05 to 20% by mass, more preferably from the viewpoint of coaggregation suppressing action and stability. It is 0.1-10 mass%, More preferably, it is 0.2-5 mass%.

  The pH of the composition for oral cavity of the present invention is 5.5 to 9 from the viewpoint of storage stability and oral mucosal irritation, but 6 to 9 is particularly preferable. A pH of 5 or less is not preferable because alkylgalactoside (formulas (A) to (C)) is decomposed. Further, when the pH exceeds 9, there is irritation to the oral mucosa. This oral mucosal irritation becomes remarkable when an anionic surfactant is blended. In order to adjust the pH of the composition for oral cavity of the present invention to 5.5-9, no component showing extreme acidity or basicity is blended, or the acidic component and the basic component are combined so as to be within the above pH range. Although it is possible, the pH adjuster used for an oral preparation can also be used. Examples of such pH adjusters include citric acid, malic acid, lactic acid, tartaric acid, succinic acid, acetic acid, phosphoric acid, pyrophosphoric acid, glycerophosphoric acid, various salts thereof such as potassium salt, sodium salt and ammonium salt, sodium hydroxide, Examples thereof include potassium hydroxide and hydrochloric acid. These can be blended alone or in combination of two or more so that the pH of the oral preparation can be adjusted to 5.5-9. The compounding quantity is 0.01-2 mass% normally. The pH of the oral composition of the present invention can be directly measured in the case of a liquid composition such as a mouthwash, but in the case of a toothpaste or the like, it is measured as a 10% by mass aqueous solution.

In the composition for oral cavity of this invention, since it contains alkyl galactoside and pH is adjusted to 5.5-9, even if it contains an anionic surfactant, mucous membrane irritation can be reduced. Here, as the anionic surfactant, higher fatty acid salt, alkyl sulfate ester salt, alkyl sulfonate salt, alkyl phosphate ester salt, polyoxyalkylene alkyl sulfate salt, polyoxyalkylene alkyl sulfonate salt, polyoxyalkylene alkyl phosphorus salt Examples include acid ester salts, N-acyl amino acid salts, alkylmethyl taurate salts, sulfosuccinic acid ester salts, and alkylbenzene sulfonates. As for carbon number of the alkyl part or aliphatic acyl part of these anionic surfactants, 8-24 are preferable.
Among these anionic surfactants, one or more selected from N-acyl sarcosine salts, alkylmethyl taurine salts and alkyl sulfates are more preferred, and N—C ₈ -C ₂₄ acyl sarcosine salts, C ₈ — One or more selected from C ₂₄ acylmethyl taurate and C ₈ -C ₂₄ alkyl sulfate are particularly preferred.

  The content of the anionic surfactant in the whole oral composition of the present invention is 0.05 to 2.0% by mass, more preferably 0.1 to 1.8% by mass, particularly 0, from the viewpoint of cleaning performance and mucosal irritation. .2 to 1.6% by mass is preferable.

  In addition, since the oral composition of the present invention contains alkyl galactoside, when menthol, which is widely used as a refreshing agent, is blended, crystals do not precipitate even under low temperature conditions, and menthol has a stable dissolution property. It is good. In addition, an anionic surfactant is usually added to improve the solubility of menthol. In the present invention, the anionic surfactant itself can reduce the mucosal irritation, and at the same time, the amount of the anionic surfactant is reduced. Even when the amount is small, the solubility of menthol is sufficiently improved. That is, since the blending amount of the anionic surfactant can be reduced, mucosal irritation is synergistically reduced.

  As menthol, l-menthol is preferable. If menthol is contained, essential oils such as peppermint oil and peppermint oil can be used. The content of menthol in the whole composition for oral cavity of the present invention is 0.01 to 2% by mass, further 0.02 to 1.5% by mass, particularly 0.05 to 1.0% by mass, from the viewpoint of a cooling effect. % Is preferred.

  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. As ingredients that can be blended, for example, wetting agents, binders, tooth strengthening agents, bactericides, enzymes, anti-inflammatory agents, blood circulation promoters, sweeteners, preservatives, coloring agents, pigments, fragrances, etc. are used as appropriate. can do. Moreover, unless the effect of this invention is impaired, surfactants other than the compound represented by Formula (A)-(C) and anionic surfactant can also be mix | blended.

  The composition for oral cavity of the present invention is prepared by a conventional method by blending the compounds represented by the formulas (A) to (C) and a pH adjuster, and if necessary, menthol, an anionic surfactant, and the sugar alcohol. Can be used for powdered toothpaste, liquid toothpaste, toothpaste, moisturized toothpaste, pasty detergent such as oral paste, liquid detergent such as mouthwash, mouthwash, gargle tablet, gum massage cream, chewing gum, troche, candy It can be made into forms, such as foodstuffs.

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 a test substance of Reference Example 7 and Examples 1 to 6 as α, β-lauryl galactoside.

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 α, β-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 (above, Dojin Pharmaceutical Co., Ltd.), C10: C14 alkyl glucoside (Cognis Japan) The coaggregation test used was a round bottom 96-well microplate (TPP), 100 μL of any Fusobacterium suspension, 50 μL of Ss or Aa suspension and 1.6% (wt / vol%). ) 50 μL of the test substance 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 (pH stability of alkyl galactoside)
Dissolved in 0.5M various buffer solutions of pH 4-10 or purified water (pH 7) so that 2% by mass of α, β-lauryl galactoside and 1% by mass of sodium lauryl sulfate (hardened castor oil only at pH 4) Thereafter, it was stored at 50 ° C. for 1 month. The decomposition rate of lauryl galactoside was determined by quantifying free galactose using HPLC.
Method for measuring free galactose Immediately after production and 10 g of the test dentifrice composition immediately after storage, weighed precisely, added 0.5 M borate buffer to make exactly 100 mL, and well shaken. A part of the solution was filtered and applied to high performance liquid chromatography (HPLC). As the HPLC column, a polymer ion exchange column was used, and as an eluent, 0.5 M borate buffer was used at 65 ° C. and an elution rate of 0.4 mL / min. The galactose was detected with an RI detector, and the quantification was performed using a calibration curve prepared in advance.

  As shown in Table 5, when the alkyl galactoside is smaller than pH 5.5, it is understood that the decomposition proceeds gradually by storing it at a high temperature for a long period of time.

Example 2 (oral mucosal irritation test)
After 0.1 seconds of addition of 0.05% by mass of α, β-lauryl galactoside to 0.1% by mass of sodium lauryl sulfate aqueous solution adjusted to pH with citric acid or sodium carbonate, the mixture was impregnated with ion-exchanged water several times. did. One hour later, 80 mL of ion exchange water was vigorously moistened in about 5 times, and the entire amount of the moist liquid was transferred to a hematocrit tube and centrifuged at 800 rpm for 3 minutes. The volume of the sediment was defined as the amount of exfoliated mucosa (Table 6). The test was conducted every three weeks by three panelists.

  As shown in Table 6, when pH 9 is exceeded, it turns out that a mucous membrane peels and mucous membrane irritation becomes strong. From Tables 5 and 6, it can be seen that the composition for oral cavity containing alkylgalactoside is stable for a long time and low in mucosal irritation by adjusting to pH 5.5-9.

Example 3 (Crystal Precipitation of Menthol at Low Temperature)
A 0.5% by mass aqueous sodium lauryl sulfate solution, a 0.8% by mass aqueous sodium lauroyl sarcosine solution, or an aqueous sodium lauroylmethyl taurate solution was prepared. To this, 1-menthol dissolved in an equal amount of propylene glycol was added to 0.35% by mass, and α, β-lauryl galactoside in Table 7 below was added so that the final concentration was 0.5% by mass. Various components were added and stirred at 60 ° C. until uniform. After cooling to room temperature, it was filled in a PET container and stored at 5 ° C. at a low temperature. Two weeks later, each sample taken out was returned to room temperature, and the presence or absence of acicular menthol crystals was visually evaluated.

  As shown in Table 7, the composition for oral cavity of the present invention containing an alkyl galactoside and an anionic surfactant improved the solubility of menthol and did not precipitate menthol crystals even when stored at a low temperature.

Example 4
The prescription of the toothpaste (pH 6.8) 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 (including 65% by mass of 1-menthol) 1% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Purified water balance
100% by mass in total

Example 5
The prescription of the toothpaste (pH 7.2) 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 (including 65% by mass of 1-menthol) 1% by mass
α, β-lauryl galactoside 0.5% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Disodium hydrogen phosphate 0.1% by mass
Sodium dihydrogen phosphate 0.1% by mass
Purified water balance
100% by mass in total

Example 6
The prescription of the toothpaste (pH 6) 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
Lauroyl sarcosine sodium 1.2% by mass
Sodium carboxymethyl cellulose 1% by mass
Malic anhydride 1% by mass
Toothpaste fragrance (including 65% by mass of 1-menthol) 1% by mass
α, β-2-ethylhexyl galactoside 0.5% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
48% sodium hydroxide solution
Purified water balance
100% by mass in total

Example 7
The prescription of the toothpaste (pH 9) 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
Lauroylmethyl taurine sodium 1.2% by mass
Toothpaste fragrance (including 65% by mass of 1-menthol) 1% by mass
α, β-undecylgalactoside 0.8 mass%
Sodium monofluorophosphate 0.7% by mass
Saccharin sodium 0.2% by mass
48% sodium hydroxide solution
Purified water balance
100% by mass in total

Example 8
The prescription of the toothpaste (pH 7.4) 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 (including 65% by mass of 1-menthol) 1% by mass
α, β-decylgalactoside 0.1% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Disodium hydrogen phosphate 0.1% by mass
Sodium dihydrogen phosphate 0.1% by mass
Purified water balance
100% by mass in total

Example 9
The formulation of the mouthwash (pH 7.8) 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 (including 65% by mass of 1-menthol) 0.2% by mass
Sodium benzoate 0.1% by mass
Disodium hydrogen phosphate 0.1% by mass
Purified water balance
100% by mass in total

Claims (6)

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 composition for oral cavity which contains the compound represented by the integer represented by -200, n shows the integer of 1-30. 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 composition for oral cavity which contains the compound represented by the number of 0-200 and y shows the number of 1-30, and is pH 5.5-9.   Furthermore, the composition for oral cavity of Claim 1 or 2 containing C4-C12 sugar alcohol.   Furthermore, the composition for oral cavity in any one of Claims 1-3 containing an anionic surfactant.   Furthermore, the composition for oral cavity of Claim 4 containing a menthol.   The oral composition according to claim 4 or 5, wherein the anionic surfactant is one or more selected from N-acyl sarcosine salts, acylmethyl taurine salts and alkyl sulfates.