JP2006182692A - Composition for oral cavity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an agent for oral cavity, excellent in a dental caries prophylactic effect. <P>SOLUTION: The composition for oral cavity contains a compound expressed by formula (A) (R is a 1-5C straight-chain or branched-chain alkyl; G is a galactose residue; and n is an integer of 1 to 30). <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a composition for oral cavity having an excellent caries prevention effect and a coaggregation inhibitor of Fusobacterium genus bacteria and caries-causing bacteria.

  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 mechanism of colonization of oral bacteria on the tooth surface is as follows. First, initial colonized bacteria such as Streptococcus oralis, Streptococcus sangais, Streptococcus gordonii, Actinomyces naeslandi, etc. are adsorbed on the enamel surface covered with a thin film (pellicle) of saliva. . These early colonization 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. In addition, it is believed that periodontal disease-related bacteria such as Actinobacillus acnomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, and the like coaggregate and colonize the Fusobacterium nucleatum. Furthermore, Takemoto et al. Suggested that Streptococcus mutans, Streptococcus sobrinus, etc., which are caries-related 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, unlike the intestinal bacteria and skin resident bacteria, consist of the oral flora that is unique to the oral cavity. Therefore, lectin-receptor-type interaction is 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 Is involved in co-aggregation. (Non-Patent Document 2)

As a means of preventing oral infections, it has hitherto been considered to be effective to inhibit the colonization of pathogenic bacteria on the tooth surface. For example, galactose or lactose can be used to inhibit 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) and the like 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

However, galactose and lactose described in Patent Document 1 are not preferable in terms of generating an acid that causes caries by oral bacteria in the mouth, and the fatty acid sugar ester described in Patent Document 2 is also a component of an oral composition. When hydrolyzed in the mouth or in the mouth, fructose and galactose are produced, which causes similar problems.
Accordingly, an object of the present invention is to provide an oral composition containing a component that has a strong coaggregation-inhibiting action against caries-causing bacteria, prevents plaque formation, and does not generate acid in the oral cavity. It is to provide.

  Therefore, the present inventor examined the co-aggregation of Fusobacterium nucleatum bacteria and caries-causing bacteria and the production of acid in the oral cavity for various components. As a result, the compound represented by the formula (A) is a potent co-agent. It has been found that an oral composition useful for preventing dental caries can be obtained by blending this because it has an aggregation-inhibiting action and does not produce an acid in the oral cavity.

  That is, the present invention provides the formula (A)

(Wherein R represents a linear or branched alkyl group having 1 to 5 carbon atoms, G represents a galactose residue, and n represents an integer of 1 to 30). An oral composition is provided.
Moreover, this invention provides the coaggregation inhibitor of the Fusobacterium genus bacteria and the caries causative microbe which use the compound represented by Formula (A) as an active ingredient.

  By using the composition of the present invention, the causative agent in dental plaque is reduced by the coaggregation inhibitory action and does not generate acid, so that plaque becomes brittle, plaque control becomes easy, prevention of caries, etc. Is possible.

The compound represented by the formula (A) used in the present invention is an ether bond in which one or more galactose residues are α-configuration or β-configuration to a linear or branched alkyl group having 1 to 5 carbon atoms. It is a compound. Examples of the linear or branched alkyl group having 1 to 5 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, and an n-pentyl group.
Although n which shows the condensation degree of galactose is an integer of 1-30, 1-6 are preferable from the point of the coaggregation inhibitory effect, and 1-3 are more preferable. Moreover, if the sugar chain terminal is a galactose residue, the middle galactose residue may be substituted with a glucose residue or the like.

  The compound represented by the formula (A) can be synthesized relatively easily from D-galactose in anhydrous alcohol in the presence of an acid catalyst such as hydrogen chloride by the Fischer method. (Bid., Vol.27, p2481)

  The compound represented by the formula (A) strongly suppresses co-aggregation of Fusobacterium genus bacteria that are resident bacteria and caries-causing bacteria. Here, examples of Fusobacterium include Fusobacterium nucleatum and Fusobacterium rouge. Examples of caries-causing bacteria include Streptococcus mutans, Streptococcus sobrinus, and the like.

  A conventionally known fatty acid sugar ester decomposes in the oral cavity to produce an acid that causes caries, but the compound represented by the formula (A) used in the present invention is used in the oral cavity as shown in Examples below. It is not decomposed inside and does not produce acid that is a source of caries.

  0.005-50 mass% is preferable, as for content in the whole composition for oral cavity of this invention of the compound represented by Formula (A), More preferably, 0.01-10 mass%, More preferably, 0.05- 5% by mass.

  The oral composition of the present invention preferably further contains a linear sugar alcohol from the viewpoint of the coaggregation suppressing effect. The linear sugar alcohol is preferably a sugar alcohol having 4 to 12 carbon atoms, and examples thereof include sorbitol, mannitol, xylitol, erythritol, palatinit, and lactitol. 4-60 mass% is preferable, and, as for content in the whole composition for oral cavity of this invention of linear sugar alcohol, More preferably, it is 10-50 mass%.

  Further, the linear sugar alcohol is preferably contained in an amount of 0.1 to 1000 parts by mass with respect to 1 part by mass of the formula (A), particularly 0.1 to 500 parts by mass for a liquid dentifrice, and 1 for a mouthwash. It is preferable to contain -1000 mass parts.

  In addition, the compound represented by the formula (A) is colorless and transparent, and has extremely good solubility in water, so that it can be easily dispersed and dissolved in low-viscosity liquid toothpastes, mouthwashes, mouthwashes, and the like. Also, there is no separation from the water layer after long-term storage. Furthermore, it is suitable as an active ingredient of a preparation that is dissolved in water at the time of use.

  In addition to the essential components described above, various known components can be blended in the oral composition of the present invention depending on its form. Known ingredients that can be blended include, for example, wetting agents, binders, dentifrice enhancers, bactericides, pH adjusters, surfactants, enzymes, anti-inflammatory agents, blood circulation promoters, sweeteners, preservatives, and coloring agents. , Pigments, fragrances and the like can be used as appropriate.

  The composition for oral cavity of this invention mix | blends the compound represented by Formula (A), can be manufactured by a conventional method, and is a toothpaste, a toothpaste, a toothpaste, a liquid toothpaste, an oral pasta, a mouthwash , Mouthwash, gargle tablets, denture cleaning tablets, gingival massage cream, chewing gum, troches, candy, etc., especially in low-viscosity liquid toothpaste, mouthwash and mouthwash, or dissolved in water Ideal for gargle tablets and denture cleaning agents.

Example 1 (coaggregation suppressing effect)
(1) Strain used Streptococcus sobrinus B13 strain was used as a caries-causing bacterium, and Fusobacterium nucleatum polymorphic ATCC 10953 strain was used as a bacterium belonging to the genus Fusobacterium.

(2) Co-aggregation measurement method Streptococcus sobrinus was cultured for 24 hours under anaerobic conditions at 37 ° C. after inoculation in a brain heart infusion liquid medium. Fusobacterium nucleatum polymorphum was inoculated in a GAM bouillon liquid medium and cultured under anaerobic conditions at 37 ° C. for 48 hours. After completion of the culture, the cells were collected by centrifugation and washed twice with a buffer solution for coaggregation (1 mM tris (hydroxymethyl) aminomethane, 0.1 mM calcium chloride, 0.1 mM magnesium chloride, 0.15 M sodium chloride). . After washing, Fusobacterium nucleatum and Streptococcus sobrinus were adjusted with a coaggregation buffer so that the absorbance (OD) at a wavelength of 600 nm was 2.0 to obtain a bacterial suspension. Test substances such as the compound represented by the formula (A) were preliminarily adjusted with a coaggregation buffer so that the final concentration was 1 to 0.05%. Other test substances are mannitol, sorbitol, xylitol, lactitol (above Towa Chemical), erythritol (Niken Chemical), reduced palatinose (Shin Mitsui Sugar), β-lauryl glucoside, sucrose monolaurate (dodojin) Lactose, galactose, sucrose, glucose, fructose, and ethyl-α-D-glucoside (manufactured by Wako Pure Chemical Industries, Ltd.) were used. Galactose laurate was produced by a known method (Japanese Patent Laid-Open No. 2000-159675). The co-aggregation test is No. Using 2 RIA tubes (Asahi Techno Glass Co., Ltd.), 400 μl of Fusobacterium nucleatum suspension, 200 μl of Streptococcus sobrinus suspension and 200 μl of 2% test substance solution were mixed in order. The presence or absence of coaggregation-inhibiting activity was allowed to stand at room temperature for 30 minutes after mixing. Coaggregation-inhibiting activity was observed for those in which no cell mass precipitation was observed (+), and a slight amount of cell mass precipitation was observed. Those having a slight coaggregation inhibitory activity (±) and those not recognized were regarded as having no coaggregation inhibitory activity (−).

(3) Results As shown in Tables 1 and 2, sucrose, glucose, fructose, ethyl-α-D-glucoside, β-laurylglucoside, and sucrose monolaurate showed clear precipitation due to coaggregation, Precipitation due to coaggregation was not observed even at low concentrations in ethyl-β-D-galactoside and α, β-butylgalactoside, and a coaggregation inhibitory effect similar to lactose, galactose or galactose laurate was observed. Also, sorbitol, xylitol, erythritol, mannitol, reduced palatinose and lactitol which are linear sugar alcohols did not show precipitation due to coaggregation, and it was clear that they have coaggregation inhibitory activity. Also

Example 2
By measuring changes in pH after applying various coaggregation inhibitors to the collected plaque, it was determined whether or not these components were decomposed in the oral cavity to produce an acid. That is, after all oral hygiene habits such as tooth brushing were stopped for one week, plaques adhering to the tooth surface were physically collected using a dental scaler. The collected plaque was immediately diluted to 5% by mass with physiological saline and dispersed to prepare a plaque suspension. Various coaggregation inhibitors were added to 0.5 ml of plaque suspension to 0.9%, and the pH was adjusted to 7 with dilute hydrochloric acid or dilute sodium hydroxide solution, and the change in pH at 37 ° C. was followed for 60 minutes. . The pH was measured using a TWIN-B212 type pH meter manufactured by Horiba.

  As a result, as shown in FIG. 1, it was found that lactose, galactose and galactose laurate were decomposed in the oral cavity to produce an acid because a pH decrease was observed immediately after mixing with the plaque suspension. On the other hand, it can be seen that ethyl-β-D-galactoside and α, β-butylgalactoside hardly change pH after addition, are not decomposed in the oral cavity by oral bacteria, and do not generate acid.

Example 3
The prescription of the liquid dentifrice of the present invention is as follows.
Sorbitol 40% by mass
Silica anhydride 25% by mass
Concentrated glycerin 10% by mass
Ethyl-β-D-galactoside 4% by mass
Sodium lauryl sulfate 1% by mass
Toothpaste fragrance 1% by mass
Hydroxyethyl cellulose 0.4% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Xanthan gum 0.1% by mass
Purified water balance
100% by mass in total

Example 4
The prescription of the liquid dentifrice of the present invention is as follows.
Lactitol 26% by mass
Silica anhydride 20% by mass
Concentrated glycerin 10% by mass
Erythritol 5% by mass
Sodium lauryl sulfate 1.2% by mass
Toothpaste fragrance 1% by mass
Ethyl-β-D-galactoside 0.5% by mass
Sodium fluoride 0.2% by mass
Saccharin sodium 0.2% by mass
Xanthan gum 0.2% by mass
Xanthan gum 0.2% by mass
Purified water balance
100% by mass in total

Example 5
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
n-Butyl galactoside (α / β = 1/1) 0.2% by mass
Fragrance for mouthwash 0.2% by mass
Sodium benzoate 0.1% by mass
Purified water balance
100% by mass in total

Example 6
The prescription of the denture cleaning agent of the present invention is as follows.
Sodium percarbonate 25% by mass
Palatinit 15% by mass
Citric acid 8% by mass
Sodium citrate 8% by mass
Edetate disodium 5 mass%
n-Butyl galactoside (α / β = 1/1) 3% by mass
Polyethylene glycol 6000 2 mass%
Magnesium stearate 1% by mass
Sodium bicarbonate remaining
100% by mass in total

It is a figure which shows the intraoral pH change after mouthwash application.

Claims (3)

Formula (A)
(Wherein R represents a linear or branched alkyl group having 1 to 5 carbon atoms, G represents a galactose residue, and n represents an integer of 1 to 30). Oral composition.   Furthermore, the composition for oral cavity of Claim 1 containing a linear sugar alcohol. Formula (A)
(In the formula, R represents a linear or branched alkyl group having 1 to 5 carbon atoms, G represents a galactose residue, and n represents an integer of 1 to 30.)
The coaggregation inhibitor of the Fusobacterium genus bacteria and the caries causative microbe which use the compound represented by this as an active ingredient.