JP2005325071A - Coaggregation inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent oral periodontal disease-related bacteria from adhering to and fixing on the tooth surface by inhibiting coaggregation of oral bacteria on the tooth surface, and to be useful for prevention and improvement of periodontal disease related diseases. I will provide a.
A coaggregation inhibitor of a Fusobacterium genus bacterium and an oral early colonization bacterium comprising mannose as an active ingredient.
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Description

  The present invention relates to a coaggregation inhibitor that suppresses coaggregation of oral bacteria on the tooth surface.

  Periodontal disease is an infectious disease of the oral cavity that is caused by the adhesion and establishment of pathogenic bacteria on the tooth surface. The mechanism of colonization of periodontal disease-related bacteria on the tooth surface is as follows. First, initial colonized bacteria such as Streptococcus oralis, Streptococcus sangais, Streptococcus gordonii, Actinomyces naeslandi, etc. Adsorbs. 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 anaerobic bacteria to obligate anaerobic bacteria, and obligate anaerobic bacteria typified by Fusobacterium bacteria co-aggregate with early-fixing bacteria. And it is thought that periodontal disease related bacteria, such as Actinobacillus acnomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, etc. co-aggregate and settle in the said genus Fusobacterium.

  Coaggregation is caused by non-specific electrostatic interactions between bacteria, lectin-receptor-type interactions, adhesion by sticky polysaccharide synthesis, and non-specific hydrophobic interactions. It plays a particularly important role in the settlement.

  As a means of preventing oral infections, it has hitherto been considered to be effective in inhibiting the colonization of pathogenic bacteria on the tooth surface. For example, coaggregation of oral bacteria using specific amino sugars Inhibits plaque formation and suppresses plaque formation (see, for example, Patent Document 1); Inhibiting plaque construction using oligosaccharides isolated from sangis (see, for example, Patent Document 2), and inhibiting bacterial aggregation using xanthan gum, gum tragacanth, guar gum, etc. (for example, Patent Document) 3), etc. have been reported.

On the other hand, mannose has been reported to inhibit periodontal disease-related bacteria from adhering to the buccal mucosa epithelial cells (see, for example, Patent Document 4), but has the effect of suppressing coaggregation of oral bacteria. That has never been known.
JP-A-6-24948 US Pat. No. 7,349,772 U.S. Pat. No. 4,855,128 JP 2001-26543 A

  The present invention prevents the adhesion and colonization of oral malodor-causing bacteria, caries-causing bacteria, and periodontal disease-related bacteria on the tooth surface by suppressing the coaggregation of oral bacteria on the tooth surface. An object of the present invention is to provide an oral preparation useful for prevention and improvement of disease-related diseases.

  The present inventors focused on the co-aggregation of oral bacteria involved in plaque formation and examined components that suppress co-aggregation. As a result, mannose was co-aggregated between oral early colonization bacteria and Fusobacterium bacteria in plaque formation. It has been found that it has an inhibitory action, prevents adhesion and colonization of Fusobacterium bacteria on the tooth surface, and is useful for the prevention and improvement of bad breath, dental caries and periodontal diseases.

  That is, this invention provides the coaggregation inhibitor of the Fusobacterium genus bacteria which use mannose as an active ingredient, and an oral early colonization bacteria.

  The coaggregation inhibitor of the present invention can suppress coaggregation of Fusobacterium bacteria and oral colonization bacteria in the oral cavity and prevent periodontal disease-related bacteria from adhering to the tooth surface. Therefore, by using this, bad breath, dental caries and periodontal disease related diseases can be prevented and improved.

  Mannose which is an active ingredient of the coaggregation inhibitor of the present invention can be obtained, for example, by decomposing a raw material containing mannan with an enzyme or an acid, or a commercially available product may be used.

Mannose suppresses co-aggregation of Fusobacterium bacteria and oral early colonization bacteria, as shown in Examples below.
In the present invention, the initial colonization bacteria in the oral cavity refers to oral bacteria that first adhere and aggregate on the enamel surface covered with a thin film of saliva (pellicles) during plaque formation. For example, Streptococcus oralis ( Streptococcus oralis) ), Streptococcus Sangaisu (Streptococcus sanguis), Streptococcus Godonyi (Streptococcus Gordonii) Streptococcus bacteria such as, include Actinomyces bacteria such as Actinomyces Naesurandi (Actinomyces naeslundii).

On the other hand, Fusobacterium spp. Are obligate anaerobic bacteria that adhere to the early colonization bacteria in plaque formation, while at the same time increasing the number of bacteria in the region of halitosis, periodontitis and acute necrotizing ulcerative gingivitis .
It is thought that attachment and colonization of bad breath, dental caries and periodontal disease related bacteria on the tooth surface is caused by co-aggregation with Fusobacterium bacteria after Fusobacterium bacteria adhere to the early colonization bacteria. If co-aggregation of Fusobacterium bacteria and early colonization bacteria in the oral cavity is suppressed, it becomes possible to prevent periodontal disease-related bacteria from adhering to and fixing on the tooth surface.

Here, Fusobacterium genus bacteria as halitosis caused bacteria, Streptococcus mutans (Streptococcus mutans) as caries-related bacteria, the periodontal disease-related bacteria such as Actinobacillus actinomycetemcomitans (Actinobacillus actinomycetemcomitans) actinolite such Bacillus bacterium, Porphyromonas gingivalis (Porphyromonas gingivalis) Porphyromonas bacteria such as, Prevotella intermedia (Prevotella intermedia) Prevotella bacteria other such, Bacteroides Fosaisasu (Bacteroides fosythus), Treponema Dentikora (Treponema denticola) and the like Can be mentioned.

  Thus, mannose can prevent bad breath, caries and periodontal disease-related bacteria from sticking to and fixing on the tooth surface. It can be used as a preparation for oral cavity to exert.

  That is, the coaggregation inhibitor of the present invention is a component used in ordinary oral compositions, such as foaming agents, foaming aids, surfactants, abrasives, bulking agents, sweeteners, preservatives, medicinal ingredients, pH. Toothpaste, liquid toothpaste, liquid toothpaste, moisturized toothpaste, mouthwash with preventive and improving effects on bad breath, dental caries and periodontal disease by appropriately blending regulators, adhesives, pigments, pigments, fragrances, etc. , Mouse spray, chewing gum and the like.

  Here, examples of the medicinal component include bactericides such as sodium fluoride, triclosan, chlorhexidine and benzethonium chloride, enzyme inhibitors such as polyphenols (glucosyltransferase inhibitory action), and anti-inflammatory agents such as indomethacin and dipotassium glycyrrhizinate. In general, those used as oral preparations can be used.

  Sweeteners include oligosaccharides or sugar alcohols such as xylo-oligosaccharides, fructooligosaccharides, galactooligosaccharides, soybean oligosaccharides, isomaltoligosaccharides, dairy oligosaccharides, lactulose, raffinose, trehalose, glucosyl sucrose, maltosilche. Claus, palatinose, maltitol, erythritol, reduced palatinose, xylitol and the like are preferable examples.

  In addition, the content of mannose in such a coaggregation inhibitor is preferably 0.001 to 10% by weight, particularly preferably 0.01 to 5% by weight from the viewpoint of production cost.

Example 1
(1) Bacterial strains Initially established bacteria ( Streptococcus sanguinis ATCC10556) and oral bacteria ( Fusobacterium sp. KSM-Fn1, accession number: FERM P-20001) were used.

(2) Cultivation and washing Initial colonized bacteria ( Streptococcus sanguinis ATCC10556) is Brain Heart Infusion Broth (Becton Dickinson), and oral bacteria ( Fusobacterium sp. KSM-Fn1) are GAM bouillon (Nissui Pharmaceutical Co., Ltd.) The cells were cultured from the logarithmic growth phase to the stationary phase under conditions of 37 ° C., 10% CO ₂ , 10% H ₂ and 80% N ₂ , and collected by centrifugation at 5000 rpm for 5 minutes. Then, after washing with PBS buffer (144 mg / L KH ₂ PO ₄ , 9 g / L NaCl, 795 mg / L Na ₂ HPO ₄ , pH 7.4) three times by centrifugation (5000 rpm, 5 minutes), it was adjusted to 1.0 at OD 600 nm.

(3) Coaggregation measurement method
After adding 20 μL of D-mannose (Wako Pure Chemical Industries) and PBS, D-glucose (Wako Pure Chemical Industries) and D-galactose (Wako Pure Chemical Industries) to a final concentration of 100 mM to a 96-well microplate, Fusobacterium 60 μL of sp. KSM-Fn1 was dispensed and stirred, and 60 μL of Streptococcus sanguinis ATCC10556 was added. Then, using a microplate reader (Molecular Device), measure the absorbance (OD600nm) for 30 minutes at 1 minute intervals, calculate the absorbance change rate Vmax (mOD / min), and calculate the relative coaggregation rate. Aggregation reaction was measured.

(4) Results As shown in FIG. 1, the relative coaggregation rate was 100% for PBS, D-glucose, and D-galactose, but 45% for D-mannose. It was.

FIG. 1 is a graph showing the coaggregation inhibitory effect of Streptococcus sanguinis ATCC10556 and Fusobacterium sp. KSM-Fn1.

Claims (4)

  Coaggregation inhibitor of Fusobacterium spp. And oral early colonization bacteria containing mannose as an active ingredient.   The coaggregation inhibitor according to claim 1, wherein the oral early colonization bacteria are Streptococcus bacteria or Actinomyces bacteria.   The coaggregation inhibitor according to claim 1, wherein the oral colonization bacteria are Streptococcus oralis, Streptococcus sangais, Streptococcus gordonii, or Actinomyces naeslandi.   The coaggregation inhibitor according to claim 1, wherein the oral colonization bacteria are Streptococcus sangais.

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