JP4709735B2 - Coaggregation inhibitor of oral bacteria - Google Patents

Description

  The present invention relates to an oral bacterial coaggregation inhibitor, an oral composition, and the like that suppresses coaggregation of oral bacteria related to the formation of plaque and is excellent in the effect of preventing dental caries and periodontal disease.

  Plaque is a sticky bacterial mass attached to the tooth surface. The formation of plaque begins with the formation of a pellicle (acquired film) composed of saliva components on the tooth surface. The pellicle is an amorphous film-like structure formed on the tooth surface, and saliva components such as glycoproteins and polypeptides are selectively adsorbed on the tooth surface. Next, bacteria such as Actinomyces viscosus adhere to the surface of the pellicle, and various bacteria attach through the attached bacteria, and these bacteria propagate to form plaque. Is done.

  The adhesion between these bacteria is called co-aggregation, and it is said that this co-aggregation makes it possible for bacteria that do not have a strong binding force to the pellicle to settle in plaque. For example, streptococcus mutans and porphyromonas gingivalis, which are the cause of dental caries and periodontal disease, do not directly bind to the pellicle, but this coaggregation causes colonization and induces dental caries and periodontal disease. It is supposed to be one of

  The plaque thus formed thickens and deposits between the teeth and at the boundary between the teeth and the gingiva. In plaque, there are acids and toxins produced by bacteria, enzymes that destroy tissues, and the like, which is one of the main causes of dental caries, gingivitis, periodontitis and the like. Therefore, suppression of plaque formation and complete removal of already formed plaque are very effective means for preventing and treating dental caries and preventing and treating periodontal diseases.

  As a means for suppressing the formation of such plaque, bactericides have been widely used. However, when this bactericidal agent is applied to the oral cavity, it is necessary to consider not only the bactericidal effect of oral bacteria but also the influence on the oral mucosa, so the blending concentration must be lowered. Such a blending concentration was never sufficient for suppressing the formation of plaque.

  In addition, a method of brushing the plaque that has been formed by brushing with a toothpaste containing an abrasive is also widely used, but it is difficult to completely remove plaque by brushing alone, and the plaque that has been left unpolished, Causes decay, gingivitis, and periodontitis. Therefore, it can be said that the effect of preventing dental caries and periodontal disease is still insufficient only by removing plaque using conventional means.

  On the other hand, erythritol is one kind of sugar alcohol mainly used for food sweeteners. In Patent Document 1, despite the presence of normal palpable sweeteners by replacing erythritol's antidepressive properties, that is, by replacing a part of the existing palatable sweeteners with erythritol. It is disclosed that it does not involve the production of excess acid. This is because erythritol is not fermented by bacteria in the mouth, especially streptococci, that is, the bacterium itself cannot metabolize erythritol, so it does not produce lactic acid that causes dental caries and also forms plaque. This is because it does not produce water-insoluble glucan.

In order to prevent colonization and propagation of pathogenic bacteria that cause dental caries and periodontal disease, it is effective to suppress coaggregation of bacteria and bacteria. Patent Document 2 discloses an oral hygiene composition containing an amino sugar as an anti-plaque agent, and amino sugars such as N-heptylgalactosylamine, N-heptyllactosylamine, and N-decyllactosylamine are bacterial aggregates. It is disclosed to exhibit inhibitory activity. However, these amino sugars have a problem that the storage stability in the composition is poor and the cost is high.
JP-A-10-33138 JP-A-6-24948

  An object of the present invention is to suppress oral bacterial coaggregation to suppress dental plaque that causes dental caries and periodontal disease, and to prevent oral bacterial coaggregation that is excellent in preventing dental caries and periodontal disease The purpose is to provide.

  The present invention is a coaggregation inhibitor for oral bacteria containing erythritol. By applying the oral bacterial coaggregation inhibitor according to the present invention to the oral cavity, it is possible to effectively suppress oral bacterial coaggregation.

  Coaggregation of oral bacteria involves specific adhesins specific to bacterial species and binding receptors, and it is considered that coaggregation occurs only between specific bacterial species. Although the mechanism by which erythritol effectively suppresses coaggregation of oral bacteria has not yet been clarified, before erythritol acts on a receptor that causes coaggregation of bacteria and bacteria, It is presumed that it was possible to prevent coaggregation.

  By applying the oral bacterial coaggregation inhibitor containing erythritol according to the present invention to the oral cavity, coaggregation of oral bacteria can be suppressed, and plaque formation can be effectively suppressed. Prevention of dental caries and periodontal disease can be achieved by suppressing the formation of plaque.

  Here, as the structure of erythritol, there are three isomers of L-erythritol, D-erythritol, and meso-erythritol, and the present invention may have any of these structures. As the erythritol used in the present invention, those produced by fermenting glucose are mainly used, and those manufactured by Nikken Chemical Co., Ltd., Mitsubishi Chemical Foods Co., Ltd., etc. can be used.

  The blending amount of erythritol is 0.1 to 80% by mass, preferably 1 to 60% by mass, particularly 10 to 50% by mass, from the viewpoint of sufficient coaggregation inhibitory effect of oral bacteria and storage stability. It is preferable.

In addition to the above-mentioned components, the oral composition of the present invention includes, for example, foaming agents, foaming aids, abrasives, wetting agents, binders, bulking agents, sweeteners, preservatives, bactericides, medicinal ingredients, and adhesives. , Pigments, dyes, fragrances and the like can be appropriately contained.
The composition for oral cavity of the present invention can be prepared in a dosage form such as a solution, gel, or paste. In addition, the coaggregation inhibitor according to the present invention can be used for oral compositions such as dentifrices, liquid dentifrices, mouthwashes, etc., or can be used for candy and chewing gum.

  Moreover, the coaggregation inhibitory effect of oral bacteria can be enhanced by further using an amino acid in combination with the product of the present invention containing erythritol. This is because, like erythritol, erythritol was able to block bacterial coaggregation by acting on a receptor that causes bacterial coagulation of bacteria before bacterial coagulation of bacteria. It is estimated.

  The amino acids here are preferably basic amino acids such as lysine, arginine, histidine, tryptophan, proline, oxyproline, and more preferably lysine and arginine from the viewpoint of cost and storage stability.

  The compounding amount of the amino acid is 0.01 to 10% by mass, preferably 0.05 to 5% by mass, particularly 0.1 to 2%, from the viewpoint of sufficient coaggregation inhibitory effect of oral bacteria and storage stability. It is preferable that it is mass%.

  Moreover, the residual property of erythritol in the oral cavity can be enhanced by further using sodium alginate in combination with erythritol or the product of the present invention containing erythritol and an amino acid. This is presumed to be due to the property that sodium alginate reacts with calcium ions to form a gel. Erythritol is easily taken up into the generated calcium alginate gel, and further, the gel adsorbs to the teeth and mucous membranes, so that the persistence in the oral cavity is increased. Estimated to be supplied from the liquid.

In this case, the blending ratio (mass ratio) of erythritol and sodium alginate is preferably 50: 1 to 250: 1, particularly 100: 1 to 200: 1.
Sodium alginate here is not affected by the ratio of manuronic acid and guluronic acid constituting alginic acid, but is commercially available from Kimika Co., Ltd., Dainippon Pharmaceutical Co., Ltd. Those having a guluronic acid (M / G ratio) of 0.5 to 2.5 can be used.

  EXAMPLES Hereinafter, although an experiment example and an Example are shown and this invention is demonstrated more concretely, these things do not limit the scope of the present invention.

<Example A> Effect of inhibiting coaggregation of oral bacteria Three types of oral bacteria (approximately 10 each) of Porphyromonas gingivalis, Actinomyces viscoccus, and Fusobacterium nucleatum ⁶ ) were added to the test tube, and 20 ml of physiological saline was added to sufficiently disperse the bacteria. Furthermore, glycerol, erythritol, xylitol, and sorbitol were added to the test tubes in which the bacteria were sufficiently dispersed, respectively, so that the concentration of the aqueous solution was 1.0% by mass. This aqueous solution was allowed to stand at 4 ° C., and the presence or absence of precipitation of the solution after standing for 30 minutes was visually observed. The results are shown in Table 1.

<Judgment criteria>
No white precipitate is observed: ○
Slightly white precipitate is observed: △
A clear white precipitate is recognized: ×

<Example B> erythritol persistence in the mouth In a soup collected from a person, a hydroxyapatite pellet (Asahi Optical Co., Ltd., 10 mm × 10 mm, hereinafter referred to as HAP) is added and stirred at 37 ° C. for 1 hour. A saliva coat HAP was prepared. The saliva-coated HAP was immersed in the test solutions A, B, C, D, E, F, G, and H shown in Table 2 and stirred for 2 minutes, and then the saliva-coated HAP was taken out. To this, 2 ml of a mixed solution of acetonitrile / water (80/20) was added and stirred sufficiently, followed by filtration with a 0.45 μm Millipore filter. The filtrate was subjected to liquid chromatographic analysis under the following conditions to quantify erythritol. The results are shown in Table 3.

<Conditions>
Analysis column: TSK-GEL Amido-80 manufactured by Tosoh Corporation (4.6 mm x 250 mm)
Eluent: acetonitrile / water (80/20)
Flow rate: 1 mL / min Column temperature: 40 ° C
Detector: Differential refractometer Injection volume: 20 μL

<Example C> Plaque formation inhibitory effect Dental plaques of 10 subjects were completely removed by dental cleaning by a dental hygienist, and then the subjects took each of the compositions shown in Examples below for 2 weeks. used. Thereafter, the use of the composition shown in the Examples for 24 hours was stopped, and after 24 hours, a dental hygienist measured the amount of plaque formed using Silness and Loe's PI (Plaque Index). The results are shown in Table 4. However, the result was shown by the average value of 10 subjects. Moreover, the composition shown in the Example was used with the following method.

<How to use>
1. Toothpaste, liquid toothpaste: About 1 g of toothpaste was applied to a toothbrush, brushed for about 2 minutes, and used 3 times a day.
2. Mouthwash: About 10 ml of mouthwash was contained in the mouth and rinsed for about 30 seconds. After each meal, it was used between meals and 6 times a day.
3. Candy: About 5 g of candy was included in the mouth and licked without chewing. After each meal, it was used between meals and 6 times a day.
4). Chewing gum: About 3 g of chewing gum was included in the mouth and chewed for about 10 minutes. After each meal, it was used between meals and 6 times a day.

<Judgment criteria>
PI = 0 to less than 20%: ◎ (high suppression effect is recognized)
PI = 20 to less than 40%: ○ (inhibiting effect is recognized)
PI = 40 to less than 60%: Δ (slightly suppressive effect)
PI = 60% or more: × (no inhibitory effect)

  As shown in Table 1, a clear white precipitate was observed in the test tube to which glycerin, xylitol, and sorbitol were added, and only a test tube to which erythritol was added had no precipitate at all and was transparent. This means that erythritol inhibited coaggregation of three types of oral bacteria: porphyromonas gingivalis, Actinomyces viscoccus, and Fusobacterium nucleatum. That is, an effect of inhibiting coaggregation of oral bacteria by erythritol was observed.

  From the results of Table 3, it was confirmed that the residual properties of erythritol were improved in the test solutions D, E, F, G, and H to which sodium alginate was added. In addition, in the test solutions D, E, and G prepared with a blending ratio (mass ratio) of sodium alginate and erythritol of 50: 1 to 250: 1, the residual properties of erythritol are further improved. In particular, sodium alginate and erythritol In the test solution D prepared at a blending ratio (mass ratio) of 100: 1 to 200: 1, the highest residual erythritol was observed.

[Comparative Example 1] Toothpaste Sorbit Solution 30
Glycerin 15
Propylene glycol 5
Sodium carboxymethylcellulose 1
Arginine 0.3
Thickening silica 8
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Abrasive silica 15
Sodium fluoride 0.21
Fragrance 1
Purified water balance
100% by mass

[Comparative Example 2] Toothpaste Sorbite Solution 30
Glycerin 15
Propylene glycol 5
Sodium alginate (M / G ratio 1.3) 0.8
Thickening silica 6
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Abrasive silica 15
Sodium fluoride 0.21
Fragrance 1
Purified water balance
100% by mass

[Comparative Example 3] Toothpaste Sorbite Solution 30
Glycerin 15
Propylene glycol 5
Sodium carboxymethylcellulose 1
Thickening silica 6
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Abrasive silica 15
Sodium fluoride 0.21
Fragrance 1
Purified water balance
100% by mass

[Comparative Example 4] Toothpaste Sorbite Solution 30
Xylitol 10
Propylene glycol 5
Carrageenan 1
Thickening silica 6
Saccharin sodium 0.1
Sodium lauryl sulfate 1.2
Calcium hydrogen phosphate 15
Sodium monofluorophosphate 0.7
Fragrance 1
Purified water balance
100% by mass

[Comparative Example 5] Liquid toothpaste glycerin 20
Xylitol 15
Propylene glycol 5
Carboxymethylcellulose sodium 0.8
Thickening silica 3
Saccharin sodium 0.15
Sodium lauryl sulfate 1.2
Aluminum hydroxide 20
Sodium monofluorophosphate 0.7
β-glycyrrhetinic acid 0.01
Fragrance 0.9
Purified water balance
100% by mass

[Comparative Example 6] Mouthwash solution Sorbit solution 10
Saccharin sodium 0.02
Denatured ethanol 10
Polyoxyethylene (60) hydrogenated castor oil 1
Fragrance 0.5
Purified water balance
100% by mass

[Comparative Example 7] Candy Minamata 40
Sorbitol 25
Aspartame 0.5
Fragrance 0.8
Reduced maltitol balance
100% by mass

[Comparative Example 8] Chewing gum Gum base 20
Glucose 20
Sorbitol 20
Xylitol 10
Fragrance 1
Water tank balance
100% by mass

[Example 1] Toothpaste Sorbite solution 20
Polyethylene glycol 600 5
Erythritol 50
Hydroxyethyl cellulose 1
Thickening silica 6
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Abrasive silica 15
Sodium fluoride 0.21
Fragrance 1
Purified water balance
100% by mass

[Example 2] Toothpaste glycerin 15
Propylene glycol 5
Erythritol 45
Arginine 0.5
Thickening silica 7
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Calcium hydrogen phosphate 15
Sodium monofluorophosphate 0.7
Benzethonium chloride 0.01
Fragrance 1
Purified water balance
100% by mass

[Example 3] Toothpaste glycerin 15
Propylene glycol 5
Erythritol 35
Sodium alginate (M / G ratio 1.3) 0.5
Thickening silica 7
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Calcium hydrogen phosphate 15
Sodium monofluorophosphate 0.7
Benzethonium chloride 0.01
Fragrance 1
Purified water balance
100% by mass

[Example 4] Toothpaste glycerin 15
Polyethylene glycol 600 5
Erythritol 40
Lysine 0.4
Sodium alginate (M / G ratio 2.0) 0.6
Thickening silica 6
Saccharin sodium 0.15
Sodium lauryl sulfate 1.5
Abrasive silica 15
Sodium fluoride 0.21
Dl-α-tocopherol acetate 0.1
Fragrance 1
Purified water balance
100% by mass

[Example 5] Liquid toothpaste Sorbit solution 10
Propylene glycol 5
Erythritol 40
Sodium alginate (M / G ratio 0.7) 0.4
Thickening silica 3
Saccharin sodium 0.15
Sodium lauryl sulfate 1.2
Aluminum hydroxide 20
Sodium monofluorophosphate 0.7
β-glycyrrhetinic acid 0.01
Fragrance 0.9
Purified water balance
100% by mass

[Example 6] Mouthwash Erythritol 20
Arginine 0.1
Sodium alginate (M / G ratio 1.3) 0.1
Saccharin sodium 0.02
Denatured ethanol 10
Polyoxyethylene (60) hydrogenated castor oil 1
Fragrance 0.5
Purified water balance
100% by mass

[Example 7] Candy Minamata 40
Erythritol 35
Lysine 0.1
Aspartame 0.5
Fragrance 0.8
Reduced maltitol balance
100% by mass

[Example 8] Chewing gum Gum base 20
Glucose 20
Erythritol 40
Sodium alginate (M / G ratio 2.2) 0.2
Arginine 0.15
Fragrance 1
Water tank balance
100% by mass

  Table 4 shows the effect of suppressing the formation of plaque in various oral compositions containing erythritol, amino acids, sodium alginate and the like according to the present invention. As shown in Table 4, since the toothpaste of Example 1 contains erythritol, an effect of suppressing the formation of plaque was observed. In the toothpastes of Examples 2 to 4 further containing an amino acid and sodium alginate, an extremely high plaque formation inhibitory effect was observed. In addition, the liquid toothpaste of Example 5, the mouthwash of Example 6, the candy of Example 7, and the chewing gum of Example 8 contain erythritol, amino acids, and sodium alginate, and therefore extremely high suppression of plaque formation. Admitted.

  On the other hand, the toothpaste of Comparative Example 1 in which erythritol and sodium alginate were not blended and only amino acids were blended, and the toothpaste of Comparative Example 2 in which only erythritol and amino acids were blended but only sodium alginate was blended, and further erythritol In the toothpaste, liquid toothpaste, mouthwash, candy, and chewing gum of Comparative Examples 3 to 8 in which no amino acid or sodium alginate was blended, no plaque formation inhibitory effect was observed.

Claims (5)

(A) Erythritol, (B) Sodium alginate and (C) A coaggregation inhibitor of periodontal disease-causing oral bacteria comprising a basic amino acid selected from lysine, arginine and histidine as an active ingredient.   The coaggregation inhibitor according to claim 1, wherein the blending ratio of erythritol to sodium alginate is 50: 1 to 250: 1.   The composition for oral cavity containing the coaggregation inhibitor of Claim 1 or 2.   A candy comprising the coaggregation inhibitor according to claim 1 or 2.   A chewing gum comprising the coaggregation inhibitor according to claim 1 or 2.