JP4842865B2 - Oral composition - Google Patents

Description

  The present invention inhibits the formation of biofilms by inhibiting the coaggregation of bacteria that form biofilms or decomposing bacterial adherents and coaggregates that have already been formed, ie, caries, periodontal disease Inhibits the growth of bacteria that cause oral diseases such as bad breath, hard tissues such as teeth and dentures, soft tissues such as tongue and cheeks, and gaps between hard and soft tissues such as periodontal pockets The present invention relates to a composition for oral cavity that can prevent oral diseases such as caries, periodontal disease, bad breath and the like by promoting the removal of mature biofilms such as dental plaque, tongue coating and denture plaque.

In order to prevent oral diseases such as caries, periodontal disease and bad breath, it is important to inhibit the formation of biofilm and to remove the biofilm already formed in the oral cavity.
Conventionally, in order to suppress the formation of a biofilm, a method of sterilizing bacteria that form a biofilm by a bactericidal agent, an antibacterial agent, an antibiotic, etc. A method for inhibiting the formation is known (Patent Document 1). Patent Document 1 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 has been shown to exhibit inhibitory activity.

  However, these methods are intended to act on bacteria floating in saliva, etc., and to adherents and aggregates (for example, microcolony etc.) that have already been formed by bacteria attaching or aggregating. It was difficult to act. In addition, long-term use of a specific bactericidal agent or antibacterial agent and application to the oral cavity at a high concentration have problems such as showing fungal substitution and harmful effects on living tissues.

  On the other hand, in order to remove mature biofilms, in addition to physical actions such as brushing with a toothbrush or ultrasonic waves, abrasives and foaming agents that are included in dentifrices, as well as medicinal agents such as enzymes and bactericides. By using in combination, biofilms formed in the oral cavity, such as plaque and tongue coating, were decomposed and removed.

  However, already mature biofilms are covered in a film form with exopolysaccharides such as insoluble glucans secreted by bacteria, allowing medicinal agents such as enzymes and fungicides to work efficiently deep into the biofilm. It was difficult. In addition, brushing with a toothbrush or the like is difficult to completely remove the biofilm formed in the gap between the tooth and tooth gap or periodontal pocket such as the toothbrush where the tip of the bristles cannot reach. There is a problem that physical force such as pressure and ultrasonic waves has a harmful effect on oral tissues such as damaging teeth and mucous membranes.

  Here, the biofilm is composed of bacterial coaggregates including pathogenic bacteria and extracellular polysaccharides. It is presumed that the formation and maturation of biofilms are deeply related to the adhesion of bacteria floating in saliva or the like on the surface of living tissues such as teeth and mucous membranes and the formation of coaggregates of bacteria. In particular, periodontal disease-related bacteria such as Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Prevotell intermedia cannot be directly colonized in living tissues, and are presumed to be established in biofilms through aggregation reactions between adhesin-receptors between bacteria (non- Patent Document 1).

  In addition, as a structural feature of mature biofilms, there is a primitive conduit-like water circulation system in the biofilm, and a network of bacteria that make up the biofilm is built through this circulation system. ing. In other words, the existence of a circulatory system of water is necessary in order for various bacteria to live efficiently in a limited nutrient environment, such as the waste of one bacterium becoming the nutrient of another bacterium. It is estimated (Non-Patent Document 2). However, no composition for oral cavity has been developed so far, focusing on the biofilm formation process and the internal structure of the formed biofilm.

  On the other hand, paragraph 0001 of Patent Document 2 discloses the anti-cariogenic properties of erythritol, and Paragraph 0002 of Patent Document 3 discloses that xylitol has a caries-preventing effect. “There are many reports on the caries-preventing effect of xylitol in academic journals, etc. It is generally accepted that the effect of xylitol is to suppress the growth of S. mutans, the causative agent of caries. (Paragraph 0004).

Further, paragraph 0010 of Patent Document 4 discloses that “caries begins when S. mutans produces water-insoluble glucan by the action of the enzyme glucosyltransferase using sugar as a nutrient source”. .
That is, the prevention of dental caries in the prior art is S. It means prevention of dental caries by inhibiting the growth of bacteria such as mutans.
However, merely inhibiting the growth of bacteria cannot significantly affect the biofilm that is being formed. In addition, even if the growth of bacteria is inhibited, it is a place for inhabiting and breeding bacteria that cause oral diseases such as touch, periodontal disease, bad breath, etc. Since the biofilm is formed, there is a problem that it is difficult to effectively prevent touch.

JP-A-6-24948 JP 10-33138 A Japanese Patent Application Laid-Open No. 11-12143 JP 2002-325557 A P.E.Korenbrander. J. Bacteriol 175 (11): 3247-52.p.3247-3252 1993 http://www.lion.co.jp/press/2002073.pdf

  The present invention inhibits the formation of a biofilm by inhibiting the co-aggregation of bacteria that form the biofilm, that is, the formation of a place where the bacteria that cause touch, periodontal disease, etc. grow. . It also breaks down bacterial adherents and coaggregates that are already formed. Furthermore, it can cause oral diseases such as coughing, periodontal disease and bad breath by promoting biofilm removal by physicochemical action by changing the internal structure of the biofilm even for mature biofilms. An object of the present invention is to prevent oral diseases such as caries, periodontal disease and bad breath by providing a composition for oral cavity that can destroy and remove the place of growth and reproduction of bacteria.

  The present invention is an oral composition for inhibiting biofilm formation or promoting biofilm removal, which comprises a sugar alcohol and / or an amino acid. That is, according to the present invention, by blending sugar alcohol and / or amino acid with the oral composition, the hard tissue such as teeth and dentures, soft tissue such as tongue and cheek, and the gap between hard tissue and soft tissue such as periodontal pocket. In the process of forming a biofilm, the formation of biofilms is inhibited by inhibiting the attachment or aggregation of bacteria, or by breaking down the already formed adherents or coaggregates. It is possible to promote the removal of the biofilm by changing the internal structure.

  The composition for oral cavity according to the present invention changes the interaction related to adhesion and coaggregation of bacteria such as electrical, van der Waalska, adhesin-receptor, etc. by the action of sugar alcohol and / or amino acid. It was possible to inhibit biofilm formation by suppressing or dissociating the reaction. In addition, by increasing the osmotic pressure outside the mature biofilm by agglutination reaction of sugar alcohol and / or amino acid, the water activity in the biofilm is reduced, so-called dehydration and other physicochemical actions, so in the biofilm By blocking the water circulation system and disrupting the network structure in the biofilm, it was possible to simultaneously promote the removal of the biofilm formed in the gaps between teeth and periodontal pockets.

  By blending sugar alcohol and / or amino acid with the oral composition according to the present invention, hard tissues such as teeth and dentures, soft tissues such as tongue and cheeks, and gaps between hard tissues and soft tissues such as periodontal pockets are formed. In the process of biofilm formation, such as dental plaque, tongue coating, denture plaque, etc. Also in the biofilm, by promoting the removal of the biofilm by changing the internal structure of the biofilm, it is possible to effectively prevent oral diseases such as caries, periodontal disease, and bad breath.

  Examples of the sugar alcohol used in the present invention include erythritol, xylitol, glucopyranosyl sorbitol, and glucopyranosyl mannitol. Examples of amino acids include basic amino acids such as lysine, arginine, histidine, tryptophan, proline, and oxyproline. From the viewpoint of cost and storage stability, lysine and arginine are more preferable.

  The content of the sugar alcohol is 0.1 to 80% by mass, further 1 to 60% by mass, particularly 10 to 50% by mass in the composition for oral cavity of the present invention, from the viewpoint of promoting biofimur removal and inhibiting formation. preferable. The content of the amino acid is 0.01 to 10% by mass, more preferably 0.05 to 5% by mass, and particularly preferably 0.1 to 5% by mass in the composition for oral cavity of the present invention, from the viewpoint of biofilm removal promotion and formation inhibitory effect and palatability. It is preferable that it is -2 mass%.

  In the present invention, the sugar alcohol and the amino acid are particularly preferably used in combination from the viewpoint of promoting biofilm removal and forming inhibition effect. In this case, the compounding ratio (mass ratio) of sugar alcohol to amino acid is preferably 0.01: 1 to 500: 1, more preferably 0.1: 1 to 200: 1, and particularly preferably 1: 1 to 100: 1. .

  In the composition for oral cavity of the present invention, a biofilm can be obtained by using one or more selected from amino sugar, monosaccharide, oligosaccharide, phosphorylated sugar and derivatives thereof in addition to sugar alcohol and / or amino acid. It is possible to enhance the effect of promoting the removal of or the effect of inhibiting the formation of biofilm. These components are presumed to have a physicochemical action such as water absorption, chelation, electrical action and anti-aggregation action, which makes it easier to change the structure of the biofilm and enhance the action of sugar alcohols and / or amino acids. Is done.

  As amino sugars, polymers such as glucosamine, galactosamine, mannosamine, N-acetylglucosamine, N-acetylgalactosamine, N-acetylmannosamine, poly-N-acetylglucosamine, hyaluronic acid, chondroitin, chondroitin sulfate, dermatan sulfate, heparan Examples include glycosaminoglycans such as sulfuric acid, heparin, and keratan sulfate, and N-acetylglucosamine, N-acetylgalactosamine, hyaluronic acid, chondroitin, and chondroitin sulfate are preferable from the viewpoint of blending stability.

  Examples of monosaccharides include glucose, galactose, fructose, mannose, xylose, arabinose, and galactose and fructose are preferable from the viewpoint of blending stability. Examples of oligosaccharides include sucrose, lactose, maltose, xylose, isomaltooligosaccharide, fructooligosaccharide, soybean oligosaccharide, galactooligosaccharide, maltooligosaccharide, xylooligosaccharide, agarooligosaccharide, chitooligosaccharide, and the like from the viewpoint of blending stability. Lactose and maltose are preferred.

  Examples of phosphorylated sugars include glycerophosphate, phosphorylated erythritol, phosphorylated glucose, phosphorylated galactose, phosphorylated inositol, phosphorylated fructose, phosphorylated mannose, phosphorylated sucrose, phosphorylated maltose, phosphorylated starch, phosphorylated mannan, etc. From the viewpoint of blending stability, glycerophosphate, erythritol monophosphate, glucose monophosphate, galactose monophosphate, inositol monophosphate, fructose monophosphate, phosphorylated starch, and phosphorylated mannan are preferable. These compounds can also be used as salts of calcium, sodium, magnesium and the like.

  The compounding ratio (mass ratio) of sugar alcohol or amino acid to amino sugar is 0.001: 1 to 50: 1, further 0.01: 1 to 20: 1, especially 0.1: 1 to 10: 1. Is preferred. The compounding ratio (mass ratio) of sugar alcohol or amino acid to monosaccharide or oligosaccharide is 0.01: 1 to 500: 1, further 0.1: 1 to 200: 1, in particular 1: 1 to 100: 1. It is preferable. The compounding ratio (mass ratio) of sugar alcohol or amino acid to phosphorylated sugar is 0.001: 1 to 50: 1, further 0.01: 1 to 20: 1, in particular 0.1: 1 to 10: 1. It is preferable. Furthermore, the total blending ratio (mass ratio) of any two or more of sugar alcohol or amino acid to amino sugar, monosaccharide, oligosaccharide and phosphorylated sugar is 0.005: 1 to 500: 1, 0.05: 1 to 200: 1, particularly 0.5: 1 to 100: 1 are preferred.

  In addition to the above components, the oral composition of the present invention includes, for example, a foaming agent, a foaming aid, an abrasive, a wetting agent, a binder, a bulking agent, a sweetener, a preservative, a pH adjuster, a fungicide, Chemicals, blood circulation promoters, anti-inflammatory agents, enzymes, pressure-sensitive adhesives, pigments, dyes, fragrances and the like can be appropriately contained.

  The composition for oral cavity of the present invention can be prepared into a dosage form such as a solution, a gel, and a paste. In addition, the oral composition according to the present invention can be used as a powder dentifrice, toothpaste, liquid dentifrice, liquid dentifrice, mouthwash, mouth spray, denture cleanser, etc. It can also be used as candy or chewing gum.

<Example A>
(Evaluation methods)
The removal effect of human oral biofilm (plaque and tongue coating) was examined according to the following method. After removing the dental plaque and tongue coating formed on the tooth surface, periodontal pocket, and tongue of 10 subjects completely by dental cleaning such as PMTC, oral cleaning such as brushing is stopped for 36 hours or more, and plaque is placed in the oral cavity. And tongue coating was formed. Then, the composition shown as an Example or a comparative example was used, respectively.
Evaluation of the amount of plaque was performed by dyeing plaque with a plaque staining solution, dividing the plaque stained surface into a smooth surface and an interdental portion, and measuring the height from the gingival margin (mm). The amount of tongue coating was measured by wet weight collected by rubbing from a certain area near the middle of the tongue. The plaque removal rate and tongue coating removal rate were calculated from the amount of plaque and tongue coating before and after application of the composition. Moreover, the composition shown as an Example or a comparative example was used with the following method.

(how to use)
Toothpaste, liquid toothpaste: About 0.5 g of toothpaste was applied to a toothbrush, and after brushing only the tooth surface for about 2 minutes, it was boiled twice with 10 ml of ion-exchanged water.
Mouthwash: About 15 ml of mouthwash was moistened for about 30 seconds, brushed only the tooth surface for about 2 minutes, and then rinsed twice with 10 ml of ion-exchanged water.

(result)
Table 1 shows the results of plaque removal rate and tongue coating removal rate of various oral compositions containing sugar alcohol, amino acid, amino sugar, oligosaccharide, phosphorylated sugar and the like according to the present invention. However, the result was shown by the average value of 10 subjects. Example 1 in which erythritol and glucopyranosyl sorbitol, which are sugar alcohols, are blended, and Example 3 in which lysine, which is an amino acid, is blended, removes plaque from Comparative Example 1 in which sugar alcohol and amino acids are not blended. Rate and tongue coating removal rate were high. Moreover, Example 2 which mix | blended glucose-6-phosphate sodium which is phosphorylated saccharide | sugar with Example 1 and Example 4 which mix | blended maltose which is oligosaccharides with Example 3 are Example 1 and Example 3. The plaque and tongue coating removal rate was improved. Example 5 containing xylitol, which is a sugar alcohol, arginine, which is an amino acid, and chondroitin sulfate, which is an amino sugar, had the highest plaque and tongue coating removal rate among all the comparative examples and examples.

  The above results show that sugar alcohols or amino acids change the network structure in the biofilm, so that the physical action such as brushing is difficult and the biofilm such as plaque and tongue coating formed on the mucous membrane such as between teeth and tongue. It is presumed that the removal was promoted, and it is considered that the function is further improved by using amino sugar, oligosaccharide, phosphorylated sugar or the like together.

<Example B>
(Evaluation methods)
The effect of inhibiting the formation of human oral biofilm (plaque and tongue coating) was examined by the following method. After completely removing the plaque and tongue coating formed on the tooth surfaces and periodontal pockets of 10 subjects by dental cleaning such as PMTC, the compositions shown in Examples and Comparative Examples described below were used, and then 24 Oral cleaning such as time brushing was stopped, and the amount of plaque and tongue coating formed was measured. To evaluate the amount of plaque, stain the plaque with plaque staining solution, measure the plaque-stained surface by the height (mm) from the gingival margin, and calculate the average value of the smooth surface and the interdental area. The amount of dirt was taken. The amount of tongue coating was measured by wet weight collected by rubbing from a certain area near the middle of the tongue. Moreover, the composition shown in the Example or the comparative example was used with the following method.

(how to use)
1. Toothpaste, liquid toothpaste: About 0.5 g of toothpaste was applied to a toothbrush, and after brushing only the tooth surface for about 2 minutes, it was boiled twice with 10 ml of ion-exchanged water.
2. Mouthwash: About 15 ml of mouthwash was moistened for about 30 seconds.

(result)
Table 2 shows the results of plaque formation amount and tongue coating formation amount of various oral compositions containing sugar alcohol, amino acid, amino sugar, oligosaccharide, phosphorylated sugar and the like according to the present invention. However, the result was shown by the average value of 10 subjects. In Example 1 in which erythritol and glucopyranosyl sorbitol, which are sugar alcohols, are blended, and in Example 3 in which lysine, which is an amino acid, is blended, plaque and Tongue formation was low. Moreover, Example 2 which mix | blended glucose-6-phosphate sodium which is phosphorylated saccharide | sugar with Example 1 and Example 4 which mix | blended maltose which is oligosaccharides with Example 3 are Example 1 and Example 3. The amount of plaque and tongue coating was further reduced. Example 5 in which xylitol, which is a sugar alcohol, arginine, which is an amino acid, and chondroitin sulfate, which is an amino sugar, were blended had the lowest amount of plaque and tongue coating formation among all the comparative examples and examples.

  The above results suggest that sugar alcohols or amino acids inhibited the formation of biofilms such as plaque and tongue liquor by suppressing bacterial adhesion and aggregation during the biofilm formation process. It is considered that the function is further improved by using phosphorylated saccharide together.

  From the above, sugar alcohols or amino acids promote the removal of biofilm and inhibit the formation by suppressing bacterial adhesion and aggregation in the process of biofilm formation. It is considered that the function is improved by further using phosphorylated saccharide together.

[Comparative Example 1] Toothpaste Sorbitol 20
Glycerin 15
Propylene glycol 5
Sodium carboxymethylcellulose 1
Thickening silica 8
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Abrasive silica 15
Sodium fluoride 0.21
Triclosan chloride 0.02
Fragrance 1
Purified water balance
100% by mass

[Comparative Example 2] Toothpaste Glucose-6-sodium phosphate 5
Sorbitol 20
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
Cetylpyridinium chloride 0.02
Dl-α-tocopherol acetate 0.1
Fragrance 1
Purified water balance
100% by mass

[Comparative Example 3] Mouthwash Glycerin 20
Saccharin sodium 0.02
Denatured ethanol 10
Polyoxyethylene (60) hydrogenated castor oil 1
Benzethonium chloride 0.01
Fragrance 0.5
Purified water balance
100% by mass

[Comparative Example 4] Mouthwash Maltose 20
Glycerin 10
Saccharin sodium 0.02
Denatured ethanol 10
Polyoxyethylene (60) hydrogenated castor oil 1
Benzethonium chloride 0.01
Fragrance 0.5
Purified water balance
100% by mass

[Comparative Example 5] Liquid toothpaste chondroitin sulfate 0.1
Sorbitol 10
Glycerin 20
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

[Example 1] Toothpaste Glucopyranosylsorbitol 20
Erythritol 20
Glycerin 15
Propylene glycol 5
Sodium carboxymethylcellulose 1
Thickening silica 8
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Abrasive silica 15
Sodium fluoride 0.21
Triclosan 0.02
Fragrance 1
Purified water balance
100% by mass

[Example 2] Toothpaste Erythritol 40
Glucose-6-phosphate 5
Glycerin 15
Propylene glycol 5
Sodium carboxymethylcellulose 1
Thickening silica 8
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Abrasive silica 15
Sodium fluoride 0.21
Cetylpyridinium chloride 0.02
Dl-α-tocopherol acetate 0.1
Fragrance 1
Purified water balance
100% by mass

[Example 3] Mouthwash Lysine 2
Glycerin 20
Saccharin sodium 0.02
Denatured ethanol 10
Polyoxyethylene (60) hydrogenated castor oil 1
Benzethonium chloride 0.01
Fragrance 0.5
Purified water balance
100% by mass

Example 4 Mouthwash Lysine 2
Maltose 20
Glycerin 10
Saccharin sodium 0.02
Denatured ethanol 10
Polyoxyethylene (60) hydrogenated castor oil 1
Benzethonium chloride 0.01
Fragrance 0.5
Purified water balance
100% by mass

[Example 5] Liquid toothpaste xylitol 10
Erythritol 10
Arginine 1
Chondroitin sulfate 0.1
Glycerin 10
Propylene glycol 5
Carboxymethylcellulose sodium 0.8
Thickening silica 3
Saccharin sodium 0.15
Sodium lauryl sulfate 1.2
Aluminum hydroxide 15
Sodium monofluorophosphate 0.7
β-glycyrrhetinic acid 0.01
Fragrance 0.9
Purified water balance
100% by mass

[Example 6] Toothpaste Xylitol 10
Erythritol 10
Arginine 1
Chondroitin sulfate 0.1
Glycerin 10
Propylene glycol 5
Sodium carboxymethylcellulose 1
Thickening silica 8
Saccharin sodium 0.1
Sodium lauryl sulfate 1.4
Abrasive silica 15
Sodium fluoride 0.21
Cetylpyridinium chloride 0.02
Fragrance 1
Purified water balance
100% by mass

Claims (2)

The following components (A), (B) and (C) ;
(A) Sugar alcohol containing the following components (a1) and (a2) : 10 to 50% by mass
(A1) erythritol,
(A2) xylitol or glucopyranosyl sorbitol (B) a basic amino acid: 0.05 to 5 wt%,
(C) containing amino sugar <br/>,
(A) Sugar alcohol: (B) Basic amino acid compounding ratio (mass ratio) is 0.01: 1 to 500: 1, and
(A) Sugar alcohol: (C) Amino sugar compounding ratio (mass ratio) is 0.001: 1 to 50: 1.
An oral composition for promoting biofilm removal by caries or bad breath-causing bacteria.   (B) The composition for oral cavity according to claim 1, wherein the basic amino acid is lysine or arginine.