JP2008297284A - Dental plaque-formation inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a dental plaque-formation inhibitor to inhibit the formation of dental plaque and to prevent the development of oral diseases caused by dental plaque. <P>SOLUTION: The dental plaque-formation inhibitor comprises a hydroxyapatite non-adsorption fraction of tragacanth gum as an active ingredient. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a plaque formation inhibitor that suppresses the formation of plaque, an oral composition, and beverages and foods.

  Plaque and calcified calculus are the cause of various oral diseases such as dental caries and periodontal disease, and therefore, plaque formation inhibitors and calculus formation inhibitors have been proposed for the purpose of preventing these diseases. Has been. Plaque is a sticky mass that adheres to the tooth surface and consists of oral flora and their products. 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 are selectively adsorbed on the tooth surface. Plaque is formed by the adsorption and growth of oral bacteria on the pellicle surface. Furthermore, when a gonococcus such as Fusobacterium is adsorbed on bacteria adsorbed on the tooth surface, plaque formation is further promoted by an adsorption reaction between oral bacteria called co-aggregation.

  Conventional antibacterial agents and antibacterial agents have been widely used as plaque formation inhibitors, and effects such as reducing the number of bacteria in the oral cavity have been reported (Non-Patent Document 1). It is difficult to maintain the effective concentration in the inside, and the effect is insufficient (Non-patent Document 2). In addition, when plaque is already present, these decrease the metabolic activity of bacteria in the plaque and promote mineral deposition, that is, calcification. On the other hand, polysaccharides such as funolan and gellan gum (Patent Document 1) have been proposed as agents that inhibit the adsorption of bacteria to the pellicle, but these agents do not suppress the formation of the pellicle itself, The effect is not always satisfactory. As calculus formation inhibitors, use of phosphorylated starch (Patent Document 2), combined use of alginic acid and a divalent metal (Patent Document 3), and the like have been proposed. All of these agents are symptomatic treatments that prevent calcium phosphate and the like from crystallizing into dental plaque in dental plaque.

Moreover, it is known that water-soluble gums and polysaccharides such as xanthan gum, tragacanth gum, and sodium alginate suppress coaggregation of oral bacteria in a bacterial culture solution (Patent Document 4). However, it is not known that a specific fraction of tragacanth gum has an excellent plaque formation inhibitory effect.
JP-A-5-139799 JP-A-4-217613 JP-A-9-175968 JP-A-1-213222 J. Periodontol., 1991, 62 (11): 649-651 Oral Surg. Oral Med. Oral Pathol., 1990 Apr .; 69 (4): 444-449

  An object of the present invention is to provide a plaque formation inhibitor, an oral composition, a food, a beverage and the like having a more excellent plaque formation inhibitory action.

  The present inventors examined the anti-plaque formation effect of tragacanth gum, and the hydroxyapatite adsorbing component in the tragacanth gum has an action of inhibiting the anti-plaque formation effect, and the fraction from which the component was removed from the tragacanth gum forms plaque formation. It was found useful as an inhibitor.

  That is, this invention provides the plaque formation inhibitor which uses the hydroxyapatite non-adsorption fraction of tragacanth gum as an active ingredient.

  Moreover, this invention provides the oral preparation composition containing the hydroxyapatite non-adsorption fraction of tragacanth gum, and food or drink, or a composition for adding these.

  The plaque formation inhibitor of the present invention inhibits plaque formation by inhibiting pellicle formation and bacterial adsorption to the tooth surface, and inhibiting and suppressing bacterial adsorption and infection in the oral cavity. Therefore, according to the present invention, it is possible to effectively prevent the occurrence of oral diseases caused by dental plaque. In addition, since the extraction of the active ingredient is based on a very simple and safe method, it is possible to supply a low-cost preparation in consideration of safety as well as significant improvement in effectiveness.

  In the present invention, as the tragacanth gum, sap of Tragacantha Tragacanth, which is a leguminous plant, can be diluted, concentrated or used as it is, or sap obtained by freeze-drying or air-drying the sap can be used. Moreover, you may use what is marketed as a food additive.

  The hydroxyapatite non-adsorbed fraction (also referred to as tragacanth gum HA non-adsorbed fraction) of the tragacanth gum of the present invention removes the fraction (also referred to as HA-adsorbed fraction) adsorbed to hydroxyapatite from the aqueous solution of tragacanth gum using hydroxyapatite. It means what is obtained by doing.

Hydroxyapatite used in the present invention is a kind of calcium phosphate represented by the chemical formula Ca ₁₀ (PO ₄ ) ₆ (OH) _2, which is a general type, Ca in which calcium is partially replaced with hydrogen. A defect type and a Ca-rich type having a high calcium substitution rate can be mentioned.
Further, when hydroxyapatite is used, it is preferable that the pH of the tragacanth gum solution is in the vicinity of 5.6 to 9 because hydroxyapatite is easily dissolved in the acidic region. Moreover, as for temperature, 15-30 degreeC is preferable.

  More specifically, for example, after adding hydroxyapatite to a tragacanth gum solution adjusted to a concentration of about 0.1% and stirring and filtering, or after passing the solution through a column packed with hydroxyapatite, The fraction that has not been adsorbed (tragant gum HA non-adsorbed fraction) can be collected and obtained by concentration to dryness or freeze drying. At this time, the solvent for washing hydroxyapatite may be water or an organic solvent in which the HA adsorption fraction is not easily eluted and a mixed solvent thereof. In addition, the tragacanth gum HA non-adsorbed fraction obtained at this time may be further purified by repeating the above-described method to remove the HA adsorbed fraction.

In addition, after removing the HA-adsorbed fraction from tragacanth gum by the above-described method, a water-soluble fraction (supernatant) or water-insoluble fraction (residue or precipitate) can be obtained. In addition, after obtaining a water-soluble or water-insoluble fraction of tragacanth gum from an aqueous solution of tragacanth gum, the HA adsorbed fraction may be removed from these by the above method.
The water-soluble fraction or water-insoluble fraction of tragacanth gum can be obtained by a known method. For example, centrifugation, filtration, organic solvent and salt precipitation, and combinations thereof can be mentioned.

  The hydroxyapatite after use may be reused after regeneration by eluting the components of the hydroxyapatite adsorbed fraction by a known method using water, a polar solvent, a mixed solvent thereof, a chelating agent of EDTA, or the like. .

  The obtained tragacanth gum HA non-adsorbed fraction may be adjusted in molecular weight and purity by known methods such as gel filtration, ion exchange chromatography, ultrafiltration membrane, and organic solvent precipitation.

  The non-adsorbed fraction of tragacanth gum thus obtained is obtained by removing the fraction of adsorbed HA (see Examples below) from the tragacanth gum, which has an inhibitory activity against the inhibition of plaque formation. It is thought to have an inhibitory effect. That is, the tragacanth gum HA non-adsorbed fraction of the present invention is considered to be effective in inhibiting the formation of pellicle and the adsorption of bacteria on the tooth surface and suppressing the formation of plaque. It can be used as an oral composition for preventing the occurrence of oral diseases caused by the above, beverages / foods or beverages / food additives, and the like.

  The tragacanth gum HA non-adsorbed fraction of the present invention can be used as it is as a plaque formation inhibitor, an additive for food and drink, etc., but a pharmaceutically usable medium such as water, methanol, ethanol, isopropanol, etc. Can be diluted and used.

  Examples of the oral composition of the present invention include dentifrice, liquid dentifrice, liquid dentifrice, moisturized dentifrice, mouthwash, mouthwash, mouth spray, tooth coating agent, denture coating agent, denture cleaning agent and the like. The oral preparation can be produced according to the general production method of the oral preparation according to the dosage form.

  The oral composition of the present invention includes various components used in the oral composition, such as sodium monofluorophosphate, sodium fluoride, potassium fluoride, stannous fluoride, sodium chloride, and aluminum lactate. , Glycyrrhetinic acid, allantochlorohydroxyaluminum, lysozyme chloride, epsilon aminocaproic acid, azulene, copper chlorophyllin sodium, copper gluconate, dl-tocopherol acetate, potassium nitrate, sodium tripolyphosphate, zeolite, dextranase, amylase, zinc citrate, chloride An active ingredient such as zinc can be added.

  Also, abrasives such as silicic anhydride, calcium hydrogen phosphate, calcium carbonate; wetting agents such as propylene glycol, polyethylene glycol, sorbitol, xylitol, maltitol, glycerin; binders such as sodium carboxymethylcellulose and carrageenan; paraoxybenzoic acid Preservatives such as methyl acid, triclosan, isopropylmethylphenol, chlorhexidine salts, cetylpyridinium chloride and other fungicides; flame retardants such as tranexamic acid; pH adjusters such as sodium hydroxide and potassium hydroxide; peppermint oil, spearmint oil, Aroma, eucalyptol, eugenol, methyl salicylate, limonene, natural fragrance materials obtained from herbs and spices, various fruit flavors and other fragrances that can be used in foods Coloring agents; may be added a foaming agent. In particular, the combined use with a bactericidal agent enhances the plaque formation inhibitory effect, and is useful as an oral composition for preventing plaque formation. Also, when used in combination with an anti-inflammatory agent, it has a preventive effect on periodontal diseases. An enhanced oral preparation composition can be obtained. Moreover, in order to prepare the oral preparation composition of the present invention, water such as purified water can be used.

  The food or beverage of the present invention has an effect of suppressing plaque formation, and can be provided as a food or beverage with an indication that it is used to suppress plaque formation. In addition to the indication that it is used to suppress plaque formation, it makes it difficult to get plaque, prevents plaque formation, keeps away bacteria that cause tooth decay, periodontal disease, and bad breath, Suppresses bacterial adsorption on teeth, suppresses tooth roughness and stickiness, keeps teeth and gums strong and healthy, suppresses acid generation, suppresses decalcification, prevents tooth decay and gingivitis, bacteria It can also be displayed that it is used for enhancing resistance from infection, focusing on saliva function, cleaning the oral environment, and the like. The food or beverage containing the plaque formation inhibitor of the present invention as an active ingredient is a person who is concerned about plaque, a person who is prone to have plaque, a person who is concerned about stickiness of the mouth, a person who is prone to decay, and gums Suitable for people who tend to swell, those who are concerned about tooth decay, periodontal disease, bad breath, and those who are thirsty. It is also effective when used before meals, after meals, before going to bed, or after brushing teeth.

  Examples of foods that can exhibit the effects of the present invention include chewing gum and refreshing confectionery in the mouth.

  The chewing gum may be any of chewing gum and bubble gum. The gum base blending and gum blending in chewing gum may be in accordance with conventional blending methods. Examples of the raw materials for gum base include natural resins, vinyl acetate resins, ester gums, synthetic gums, natural waxes, emulsifiers, and calcium carbonate. These are selected and blended according to the type of chewing gum.

  The chewing gum is added to the gum base as described above by adding the non-adsorbed fraction of the tragacanth gum HA of the present invention, sugars, nutrients, fragrances and the like and mixing them by a conventional method.

  Here, as saccharides, monosaccharides such as glucose, disaccharides such as fructose and lactose, oligosaccharides such as xylooligosaccharide and fructooligosaccharide, reduced maltose starch syrup (maltitol), xylitol, erythritol, sorbitol, lactitol, palatinit, Examples thereof include sugar alcohols such as mannitol.

  As the fragrance, fat and oil fragrances such as natural fragrances and synthetic fragrances are suitable, but are not particularly limited. Examples include mint flavors (peppermint, spearmint, menthol, etc.), fruit flavors (citrus, mixed fruit, strawberry, grape, etc.), spice flavors (cinnamon, clove, anethole, licorice, etc.).

  Moreover, the refreshing confectionery in the mouth can be manufactured according to a general manufacturing method according to the dosage form such as candy and tablet confectionery. That is, the candy is a candy dough containing the tragacanth gum HA non-adsorbed fraction of the present invention, and the candy dough is a saccharide, and optionally dairy products, fats and oils, fruits, seeds, starch, flour, acidulant , Scented in a bowl shape using a blend of flavorings.

  Examples of the candy include hard candy and soft candy. Further, examples of the hard candy include dough candy, drop, pull candy and the like. Examples of the soft candy include caramel and nougat.

  In addition, tablet confections containing the plaque formation inhibitor of the present invention include saccharides powdered or granulated with an excipient such as dextrin and starch together with an emulsifier such as gum arabic and sucrose fatty acid ester as a lubricant, And it can manufacture by adding the tragacanth gum HA non-adsorption fraction of this invention, and making it into a tablet with a tableting machine.

  Examples of the beverage containing the plaque formation inhibitor of the present invention include soft drinks, vegetable / fruit juice beverages, alcoholic beverages, milk beverages, lactic acid bacteria beverages, teas, and coffee beverages. Antioxidants, fragrances, inorganic acids, inorganic acid salts, inorganic salts, pigments, emulsifiers, preservatives, seasonings, sweeteners, acidulants, fruit juice extracts, vegetable extracts, and nectar extracts that are generally blended in beverages Additives such as lactic acid bacteria, pH adjusters, and quality stabilizers may be used alone or in combination.

  Here, examples of the sweetener include sugar, glucose, fructose, isomerized liquid sugar, glycyrrhizin, stevia, aspartame, fructooligosaccharide, galactooligosaccharide, and other oligosaccharides such as cyclodextrin. Examples of acidulants include fruit juices extracted from natural ingredients, citric acid, tartaric acid, malic acid, lactic acid, fumaric acid, phosphoric acid and the like. Examples of inorganic acids and inorganic acid salts include phosphoric acid, disodium phosphate, sodium metaphosphate, and sodium polyphosphate.

The content of the tragacanth gum HA non-adsorbed fraction in the above-mentioned preparations containing the tragacanth gum HA non-adsorbed fraction of the present invention is 0.0005 to 0.1% by mass, further 0.001 to 0.1% by mass, particularly 0.001. When it is -0.05 mass%, administration is also easy and preferable. Further, the dose per adult (60 kg) is preferably 0.00001 to 5 g / day, particularly preferably 0.0001 to 1 g / day as the non-adsorbed fraction of tragacanth gum.
The plaque formation inhibitor and oral composition of the present invention have the effect of preventing bacterial infection in the oral cavity when administered to infants and the like in which oral bacteria are not established.

<Example 1>
<Method for producing tragacanth gum HA adsorbed fraction>
After preparing 200 mL of a commercially available crude tragacanth gum (made by Gokyo Sangyo) aqueous solution so as to have a concentration of 0.1%, 10 g of hydroxyapatite beads (Pentax Co., Ltd., 500 μmφ) was added, and the mixture was stirred at 20 ° C. for 2 hours (pH 6-7). ) The mixture was stirred and separated into a supernatant (tragant gum HA non-adsorbed fraction) and the beads (HA adsorbed fraction) by filtration. Thereafter, only the beads were decalcified with EDTA, desalted by dialysis, and freeze-dried to obtain HA adsorbed fraction powder, which was 10% by mass of tragacanth gum.

<Competitive inhibition test for water-insoluble fraction of HA adsorbed fraction>
The tragacanth gum water-insoluble fraction 0.01% solution prepared by the following method was used for the above-mentioned tragacanth gum HA adsorption fractions of 0,0.002,0.004,0.006,0.008 and 0.01%. An aqueous solution prepared to an arbitrary concentration was added to prepare a test substance having a mass ratio of 100 to 50: 0 to 50: 50% of the tragacanth gum water-insoluble fraction: HA adsorption fraction. The prepared test substance was assayed for bacterial adsorption inhibition activity by the following method.

<Method for producing water-insoluble fraction of tragacanth gum>
A commercially available crude tragacanth gum aqueous solution was prepared to a concentration of 0.1%, and then centrifuged (1800 × g, 10 minutes, room temperature), a water-insoluble fraction (precipitate fraction) and a water-soluble fraction (supernatant fraction). Fraction). Each fraction was lyophilized to obtain a dried product.
As a result, the mass ratio of the dried product was water-insoluble fraction: water-soluble fraction = 7: 3.

<Measurement of bacterial adsorption inhibitory activity>
The bacterial adsorption inhibition effect of the test substance was measured by the following method.
10 μCi / mL methylated [ ³ H] -thymidine 0.2 wt% glucose-containing brain heart infusion medium (DIFCO) (10 mL) was inoculated with 10 μCi / mL preserved microbial cells isolated from the human oral cavity. Time anaerobic culture. After washing three times with buffered KCl solution (1 mM phosphate buffer containing 50 mM potassium chloride, 1 mM magnesium chloride, 0.1 mM magnesium chloride), 1 × 10 ⁹ CFU / mL was added to the buffered potassium chloride solution containing 5 mg / mL bovine serum albumin. ³ H-labeled S. mutans solution was dispersed at a concentration.

Hydroxyapatite flat plate (Pentax Co., Ltd., 1 cm × 1 cm × 2 mm) was treated at 37 ° C. for 1 hour with 1 mL of each test substance aqueous solution prepared above. After washing with 2 mL of buffered potassium chloride solution, treatment was performed overnight at 4 ° C. in 0.5 mL of parotid saliva collected from healthy men. After washing twice with 2 mL of buffered potassium chloride solution, 0.5 mL of 5 mg / mL bovine serum albumin-containing buffered potassium chloride solution and 0.5 mL of the ³ H-labeled S.mutans solution were added and treated at 37 ° C. for 1 hour. After washing three times with a buffered potassium chloride solution, the hydroxyapatite flat plate was treated at 70 ° C. for 1 hour in 1 mL of 2M aqueous sodium hydroxide solution. After neutralization with 1 mL of 2N hydrochloric acid, ³ H radioactivity was measured with a liquid scintillation counter, and the bacterial adsorption number (X) was calculated.

  In the above operation, A is the number of bacteria adsorbed when the same treatment is performed using 1 mL of distilled water instead of the aqueous solution. Also, B is the number of bacteria adsorbed when the same treatment is performed using 1 mL of distilled water instead of the aqueous solution and 0.5 mL of buffered potassium chloride solution instead of parotid saliva.

(Equation 1)
Bacterial adsorption inhibition rate I (%) = [(AX) / (AB)] × 100

In the above bacterial adsorption inhibition activity measurement (final each test substance concentration 0.01%), the tragacanth gum water-insoluble fraction has a bacterial adsorption inhibition effect of about 90%, and the bacterial adsorption inhibition of about 70% of the crude tragacanth sap. It is recognized that it is higher than the effect (FIG. 1).
When the tragacanth gum HA adsorption fraction was added to this, it was confirmed that the bacterial adsorption inhibition effect was suppressed as the mass ratio of the tragacanth gum HA adsorption fraction increased (FIG. 2).
Therefore, the HA adsorbed fraction has inhibitory activity against the bacterial adsorption inhibiting action, and the HA adsorbed fraction removed from the tragacanth gum (tragant gum non-HA adsorbed fraction) has a bacterial adsorption inhibiting action, that is, plaque. It is thought that there is a formation inhibitory action.

<Example 2>
A tragacanth gum HA non-adsorbed fraction (supernatant) was obtained in the same manner as in Example 1 except that 20 g of hydroxyapatite beads were mixed with 100 mL of a 0.1% crude tragacanth gum solution, and a bacterial adsorption inhibition activity test was performed. . In the test, test substances of Control (no addition), a crude tragacanth gum aqueous solution, and a tragacanth gum HA non-adsorbed fraction were used.
FIG. 3 shows the number of bacteria adsorbed by each test substance in the bacteria adsorption inhibition activity measurement. Compared with Control, the bacterial adsorption activity was significantly suppressed in the crude tragacanth gum aqueous solution (P <0.05) and the tragacanth gum HA non-adsorbed fraction (P <0.01).
Further, the non-adsorbed fraction of tragacanth gum HA showed a tendency to further suppress the adsorption of bacteria as compared with the crude tragacanth gum aqueous solution.

<Example 3 Dentifrice>
Tragacanth gum HA non-adsorbed fraction 0.1% by mass
Silica 30
Sorbitol 30
Sodium lauryl sulfate 1.0
Carboxymethylcellulose 1.0
Saccharin 0.1
Perfume appropriate amount water 100 in total

<Example 4 mouthwash>
Tragacanth gum HA non-adsorbed fraction 0.1% by mass
Ethanol 20
Sodium pyrophosphate 2.0
Saccharin 0.1
Perfume appropriate amount water 100 in total

<Example 5 chewing gum>
Tragacanth gum HA non-adsorbed fraction 0.1% by mass
Gum base 20
Glucose 20
Sorbitol 20
Xylitol 10
Perfume appropriate amount Minamata 100

<Example 6 Candy>
Tragacanth gum HA non-adsorbed fraction 0.1% by mass
Minamata 40
Sorbitol 25
Aspartame 0.5
Perfume appropriate amount Reduced maltitol all 100

<Example 7 Tablets>
Tragacanth gum HA non-adsorbed fraction 0.1% by mass
Granule No. for direct hitting 209 * (Fuji Chemical Co., Ltd.) 45
Crystalline cellulose 40
CMC calcium 8
Perfume appropriate amount Magnesium stearate 100
* Fine No. for direct hitting 209 (magnesium aluminate metasilicate 20% by mass, corn starch 30% by mass, lactose 50% by mass)

<Example 8 Beverage>
Tragacanth gum HA non-adsorbed fraction 0.1% by mass
Erythritol 0.8
Aspartame 0.5
Grapefruit juice 0.1
Perfume appropriate amount water 100 in total

  As for the oral preparation composition and foodstuff of this invention of Examples 3-8, the outstanding plaque formation inhibitory effect was recognized by all.

Bacterial adsorption inhibition rate (%) of crude tragacanth, water-soluble (soluble) fraction and water-insoluble (insoluble) fraction (each final concentration 0.01% aqueous solution). Bacterial adsorption inhibition rate (%) of insoluble fraction aqueous solution (0.01% concentration) to which each HA adsorption (HAP) fraction aqueous solution (0 to 0.01% concentration) was added. Bacterial adsorption number of Control (no addition), crude tragacanth gum and HA non-adsorbed fraction.

Claims (5)

  A plaque formation inhibitor comprising the non-adsorbed fraction of tragacanth gum as hydroxyapatite.   An oral preparation composition comprising a hydroxyapatite non-adsorbed fraction of tragacanth gum.   A food or beverage containing a non-adsorbed fraction of tragacanth gum hydroxyapatite.   4. The food or beverage according to claim 3, wherein the food or beverage has an effect of suppressing plaque formation, and indicates that it is used to suppress plaque formation.   A composition for addition of food or beverage containing a non-adsorbed fraction of tragacanth gum hydroxyapatite.

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