JP4602922B2 - Plaque formation inhibitor - Google Patents

Description

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

  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). Also, if plaque is already present, they reduce the metabolic activity of bacteria in the plaque and promote mineral deposition, ie 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.

In addition, it is known that water-soluble gums and polysaccharides such as xanthan gum, tragacanth gum, sodium alginate and the like suppress coaggregation of oral bacteria in a bacterial culture (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-01-213222 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 tragacanth gum water-insoluble fraction has an excellent anti-plaque formation effect compared to the tragacanth gum solution and the tragacanth gum water-soluble fraction, to prevent oral diseases. It was found to be useful as a material.

  That is, this invention provides the plaque formation inhibitor which uses a tragacanth gum water-insoluble fraction as an active ingredient.

  The present invention also provides an oral preparation composition containing a water-insoluble fraction of tragacanth gum and a food or beverage 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 tragacanth (Tragacantha, Tragacanth), which is a leguminous plant, can be diluted, concentrated, or used as it is, or sap of the sap can be used by freeze drying or air drying. Moreover, you may use what is marketed as a food additive.

  As a method for obtaining the water-insoluble fraction of tragacanth gum of the present invention, a known method can be used. For example, the supernatant liquid (water-soluble fraction) was separated from the aqueous solution of tragacanth gum by filtration, filtration, precipitation with an organic solvent such as ethanol or acetone, salt precipitation such as sodium chloride or calcium acetate, and a combination thereof. It can be obtained as a precipitate (also called residue) (insoluble fraction). In addition, you may refine | purify the obtained insoluble fraction by repeating said method.

More specifically, for example, the crude tragacanth gum aqueous solution prepared to a concentration of about 0.1% can be obtained by centrifuging and collecting the precipitate. Further, the organic solvent precipitation and the salt precipitation may be performed together. Centrifugation may be performed at 4 to 30 ° C., more preferably 10 to 25 ° C., 1000 to 15000 g for 5 to 30 minutes, and more preferably 1500 to 5000 g for 10 to 20 minutes.
The obtained water-insoluble fraction can be used as it is or after drying or solution, after diluting or concentrating according to the target product.

  The water-insoluble fraction of tragacanth gum thus obtained was an excellent inhibition of bacterial adsorption compared to the tragacanth gum solution and the water-soluble tragacanth fraction in a bacterial adsorption inhibition test using a hydroxyapatite flat plate, as shown in Examples below. Has an effect. That is, the water-insoluble fraction of tragacanth gum of the present invention inhibits pellicle formation and bacterial adsorption to the tooth surface, and is thought to be effective in suppressing the formation of plaque, resulting from a plaque formation inhibitor and plaque. It can be used as an oral composition for preventing the occurrence of oral diseases, foods or beverages, food and drink additives and the like.

  The water-insoluble fraction of tragacanth gum of the present invention can be used as it is as a plaque formation inhibitor, an additive for foods and drinks, etc., but in a pharmaceutically usable medium such as water, methanol, ethanol, isopropanol, etc. It 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.

  In the oral preparation of the present invention, various components used in the oral preparation, such as sodium monofluorophosphate, sodium fluoride, potassium fluoride, stannous fluoride, sodium chloride, 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 gum 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.

  Chewing gum is added to the above-described gum base with the water-insoluble fraction of tragacanth gum of the present invention, sugars, nutrients, flavors, and the like, and mixed in a conventional manner.

  Here, the saccharides include 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, and palatinit. And sugar alcohols such as mannitol.

  As the fragrance, fat and oil fragrances such as natural fragrance and synthetic fragrance are suitable, but are not particularly limited. Examples thereof 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 water-insoluble fraction of the present invention, the candy dough is a saccharide, and optionally dairy products, fats and oils, fruits, seeds, starch, flour, acidulant, A blended flavoring material is used as a raw material and boiled in a bowl shape.

  Examples of the candy include hard candy and soft candy, and examples of the hard candy include dough candy, drop, pull candy and the like, and 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 emulsifier such as gum arabic and an excipient such as dextrin and starch, and sucrose fatty acid ester as a lubricant, And it can manufacture by adding the tragacanth gum water-insoluble 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 cyclodextrin as other oligosaccharide. Examples of acidulants include fruit juices extracted from natural ingredients, citric acid, tartaric acid, malic acid, lactic acid, fumaric acid, and phosphoric acid. Examples of inorganic acids and inorganic acid salts include phosphoric acid, disodium phosphate, sodium metaphosphate, and sodium polyphosphate.

The content of the insoluble fraction of tragacanth gum in the above-mentioned preparations containing the water-insoluble fraction of tragacanth gum of the present invention is 0.0005 to 0.1% by mass, further 0.001 to 0.1% by mass, especially 0.001 to 0. If it is 05 mass%, administration is easy and preferable. Moreover, the dosage per adult (60 kg) is preferably 0.00001 to 5 g / day, particularly preferably 0.0001 to 1 g / day, as a water-insoluble 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 Tragant gum fractionation method>
After preparing a commercially available crude tragacanth gum aqueous solution to a concentration of 0.1%, it was centrifuged (1800 × g, 10 minutes, room temperature), an insoluble fraction (precipitate fraction) and a water-soluble fraction (supernatant fraction). ). Each fraction was lyophilized to obtain a dried product.
As a result, the mass ratio of the dried product was insoluble fraction: water-soluble fraction = 7: 3.

<Example 2 Bacterial adsorption inhibition effect of insoluble fraction>
The bacterial adsorption inhibition effect of the test substance was measured by the following method.
S.mutans preserved cells isolated from the human oral cavity are inoculated into 10 mL of brain heart infusion medium (DIFCO) containing 10 μCi / mL methylated [ ³ H] -thymidine 0.2 wt% glucose, and incubated at 37 ° C. for 24 hours. Time anaerobic culture. After washing three times with a buffered KCl solution (50 mM potassium chloride, 1 mM magnesium chloride, 0.1 mM magnesium chloride-containing 1 mM phosphate buffer), 1 × 10 ⁹ CFU / mL was added to a buffered potassium chloride solution containing 5 mg / mL bovine serum albumin. ³ H-labeled S. mutans solution was dispersed at a concentration.

A hydroxyapatite flat plate (manufactured by Pentax Co., Ltd., 1 cm × 1 cm × 2 mm) was treated with 1 mL of each 0.01% aqueous test substance solution at 37 ° C. for 1 hour. The test substances were the insoluble fraction solution, the soluble fraction solution, and the commercially available crude tragacanth gum aqueous solution described in Example 1. After washing with 2 mL of buffered potassium chloride solution, it was treated 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 above 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

  As a result, the insoluble fraction exhibited a markedly high effect with a bacterial adsorption inhibition rate of 90% or more (FIG. 1). The insoluble fraction improved the effect statistically significantly over the commercially available crude tragacanth gum, while the soluble fraction did not differ.

<Examples 3 to 8>
The oral agent composition and food of Examples 3 to 8 below were prepared using the tragacanth insoluble fraction. As for the oral preparation composition of this invention of Examples 3-8, and the drink and foodstuff, the outstanding plaque formation inhibitory effect was recognized by all.

<Example 3 Dentifrice>
Tragacanth gum water-insoluble 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 water-insoluble fraction 0.1% by mass
Ethanol 20
Sodium pyrophosphate 2.0
Saccharin 0.1
Perfume appropriate amount Water 100

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

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

<Example 7 Tablets>
Tragacanth gum water-insoluble fraction 0.1% by mass
Direct hit fine particle No.209 * (Fuji Chemical Co., Ltd.)
Crystalline cellulose 40
CMC calcium 8
Perfume appropriate amount Magnesium stearate 100
* Direct granule No.209 (magnesium aluminate metasilicate 20 mass%, corn starch 30 mass%, lactose 50 mass%)

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

Bacterial adsorption inhibition activity (0.01% concentration of each) of crude aqueous tragacanth gum solution, water-soluble fraction solution, and water-insoluble fraction solution.

Claims (5)

A plaque formation inhibitor comprising as an active ingredient a precipitate fraction obtained by centrifuging a crude tragacanth gum aqueous solution . An oral composition containing a precipitate fraction obtained by centrifuging a crude tragacanth gum aqueous solution . A food or beverage containing a precipitate fraction obtained by centrifuging a crude tragacanth gum aqueous solution .   The food or beverage according to claim 3, wherein the food or beverage has an effect of suppressing the formation of plaque and is used for suppressing the formation of plaque. A composition for addition of food or beverage containing a precipitate fraction obtained by centrifuging a crude aqueous solution of tragacanth gum .

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