JP2007320926A - Plaque formation inhibitor, or cariostatic agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new plaque formation inhibitor using an plant extract, to provide a cariostatic agent, to provide a composition for oral cavities, and to provide a food or drink for preventing dental caries. <P>SOLUTION: This plaque formation inhibitor is characterized by containing a compound represented by the general formula (1) [R is H or a lower alkyl; (n) is 1 or 2] contained in an alcohol extraction fraction of Angelica keiskei or its salt as an active ingredient. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a plaque formation inhibitor and an anti-cariogenic agent, and a composition for oral cavity and a food and drink for the prevention of dental caries or oral disease using these as active ingredients. More specifically, the present invention relates to a plaque formation inhibitor and an anti-cariogenic agent comprising a plant-derived component as an active ingredient, and the oral composition and caries-preventing food and drink containing these.

  Caries (caries) is a phenomenon in which caries bacteria in the mouth generate acid using sucrose as a nutrient source, and the tooth dissolves with this acid. Although there are various theories about the detailed cause of the caries, at present, it is a sticky, insoluble polysaccharide produced by caries bacteria (eg, Streptococcus mutans) (this is called “insoluble glucan”). It is said that dental caries (cavities) start by binding to the tooth surface, which becomes plaque and accumulates on the tooth surface. In this plaque, many bacteria including the carious bacteria described above coexist and propagate, and the enamel on the tooth surface is decalcified by the action of organic acids produced by the metabolism of these bacteria. Progresses. In addition to such caries (decayed teeth), dental plaque can cause bad breath and can develop into various oral diseases such as periodontal disease, periodontitis, and alveolar pus leakage.

  Therefore, in order to prevent dental caries and prevent periodontal disease, periodontitis, and alveolar pus leakage due to the progression of dental caries, plaque that adheres to the tooth surface is removed by brushing the teeth. In addition, it is effective to prevent the formation of plaque by preventing the production of insoluble glucan by inhibiting the growth of carious bacteria (Streptococcus mutans) in the oral cavity.

  From such a viewpoint, in recent years, an oral composition having a caries preventive effect by incorporating a substance having an action of suppressing the growth of carious bacteria (Streptococcus mutans) and a substance of suppressing plaque formation as an active ingredient. A plurality of foods and foods and drinks have been proposed (see, for example, Patent Documents 1 to 4).

On the other hand, tomorrow is a celery family plant that has long been prized as a medicinal herb with strong, strong, longevity and long life. Tomorrow has traditionally been known to be rich in vitamins, minerals, high-quality protein and dietary fiber, but in recent years, medically, chalcones, which are the main components in toast's yellow juice, Bactericidal action against Gram-positive bacteria (Non-patent document 1), anti-ulcer and gastric acid secretion inhibiting action (Non-patent document 2), thromboxane A2 production inhibitory action (Non-patent document 3), vasorelaxant action (Non-patent document 4), It has been proved that there are useful pharmacological actions such as antiallergic action (Non-patent document 5), anti-HIV action (Non-patent document 6), tumor promoter suppressing action and antitumor action (Non-patent documents 7 to 9). . However, tomorrow and the chalcone component contained therein are not known to have a caries bacterial growth inhibitory effect or a plaque formation inhibitory effect.
Japanese Patent Laid-Open No. 04-221308 JP 2001-114694 A JP 2003-81847 A JP 2005-82568 A Y. Inamori et al., Chem. Pharm. Bull., 39, 1604 (1991) S.Murakami et al., J. Pharm. Pharmacol., 42, 723 (1990) T. Fujita et al. Research Communication in Chemical Pathology and Pharmacology, 77, 227 (1992) M. Matsuura et al., Planta Med., 67, 320 (2001) Koji Tanaka, Kimie Baba, Natural Medicines, 55, 32 (2001) Keisuke Yusa et al., Abstracts of the 113th Annual Meeting of the Pharmaceutical Society of Japan 3, 6 (1993) T.Okuyama et al., Planta Med., 57, 242 (1991) T. Akihisa et al., Cancer Letter, 201, 133 (2003) Y.kimura et al., Planta Med., 70, 211 (2004)

  One of the objects of the present invention is to provide a plaque formation inhibitor or an anti-cariogenic agent comprising a substance safe for the human body as an active ingredient. More specifically, to provide a plaque formation inhibitor or an anti-cariogenic agent comprising as an active ingredient a substance that can be safely blended in oral compositions such as mouthwashes and dentifrices as well as in foods and drinks. With the goal. Another object of the present invention is to prevent oral cavity such as caries and periodontal disease, gingivitis and alveolar pyorrhea by inhibiting the growth of anti-cariogenic bacteria and generation of dental plaque. It is providing the composition for food and drinks.

  The inventors of the present invention have been diligently studied to achieve the above object, and have been used as medicinal herbs for a long time in plants of the family Apiaceae, and in recent years, many useful pharmacological actions (bactericidal action against Gram-positive bacteria) To the sap and solvent extract of tomorrow where anti-ulcer action, gastric acid secretion inhibitory action, thromboxane A2 production inhibitory action, vascular relaxation action, antiallergic action, anti-HIV action, carcinogenic promoter inhibitory action, etc. are known, It has been found that it has an excellent inhibitory effect on plaque formation and an inhibitory effect on the growth and proliferation of Streptococcus mutans, which is a carious bacterium.

(In the formula, R represents a hydrogen atom or a lower alkyl group, and n represents 1 or 2.)
It confirmed that it was a compound shown by.

The present invention has been completed based on such findings and includes the following embodiments:
(1) Plaque formation inhibitor and anti-cariogenic agent General formula (1)

(In the formula, R represents a hydrogen atom or a lower alkyl group, and n represents 1 or 2.)
The plaque formation inhibitor which contains the compound shown by these, or its salt as an active ingredient.
Item 2. Item 2. The plaque formation inhibitor according to Item 1, which comprises a plant component containing the compound (1) or a salt thereof or a processed product thereof.
Item 3. Item 3. The plaque according to Item 2, wherein the plant component or processed product thereof is any one selected from the group consisting of a solvent extract of tomorrow leaf roots, stems and sap, tomorrow leaf sap, and a concentrate of tomorrow leaf sap. Formation inhibitor.

  Item 4. General formula (1)

(In the formula, R represents a hydrogen atom or a lower alkyl group, and n represents 1 or 2.)
An anti-cariogenic agent containing the compound represented by the above or a salt thereof as an active ingredient.
Item 5. Item 5. The anticariogenic agent according to Item 4, comprising a plant component containing compound (1) or a salt thereof or a processed product thereof.
Item 6. Item 6. The resistance according to Item 5, wherein the plant component or processed product thereof is any one selected from the group consisting of a solvent extract of tomorrow leaf roots, stems and sap, tomorrow leaf sap, and a concentrate of tomorrow leaf sap. Carbicide.

(2) Oral composition item 7. It contains at least one selected from the group consisting of the plaque formation inhibitor described in Items 1-3 and the anti-cariogenic agent described in Items 4-6 as an active ingredient for prevention of dental caries or oral disease. An oral composition.
Item 8. An oral composition for preventing caries or oral disease is produced by using at least one selected from the group consisting of the plaque formation inhibitor described in Items 1-3 and the anti-cariogenic agent described in Items 4-6. How to use to

(3) Food and drink It contains at least one selected from the group consisting of the plaque formation inhibitor described in Items 1-3 and the anti-cariogenic agent described in Items 4-6 as an active ingredient for prevention of dental caries or oral disease. Food and drink.
Item 10. In order to produce a food or drink for preventing caries or oral disease, at least one selected from the group consisting of the plaque formation inhibitor described in Items 1-3 and the anti-cariogenic agent described in Items 4-6. How to use.

  In the present specification, food and drink include not only foods and drinks by humans but also animals that may cause oral diseases such as caries, periodontal disease, gingivitis, and alveolar pyorrhea (for example, livestock and pets). Including feed or food.

  The plaque formation inhibitor and the anti-cariogenic agent of the present invention have an excellent pharmacological action and the compound (1) contained in tomorrow, which has been edible since ancient times, as an active ingredient, and are excellent in safety. At the same time, it is comparable to or better than known plaque formation inhibitors and anti-cariogenic agents such as cetylpyridinium chloride and thymol, and has superior anti-cariogenic activity and anti-cariogenic activity (antibacterial activity against anti-cariogenic bacteria) It is characterized by having. Therefore, according to the present invention, by providing the plaque formation inhibitor or anti-cariogenic agent of the present invention as an active ingredient, an oral composition having a high safety while having an excellent caries prevention effect is provided. can do. Furthermore, the plaque formation inhibitor or anti-cariogenic agent of the present invention can be added to foods and drinks from the above points, and as a result, foods and drinks having an excellent caries-preventing action can be provided. .

  Moreover, according to the plaque formation inhibitor, anti-cariogenic agent, oral cavity composition for preventing dental caries or foods and drinks according to the present invention, by suppressing the formation of plaques and the growth of caries-causing bacteria In addition to caries, oral diseases such as bad breath, periodontal disease, gingivitis and alveolar pyorrhea can be effectively prevented.

(1) Plaque formation inhibitor and anti-cariogenic agent The plaque formation inhibitor and the anti-cariogenic agent according to the present invention have the general formula (1)

(In the formula, R represents a hydrogen atom or a lower alkyl group, and n represents 1 or 2.)
Or a salt thereof as an active ingredient.

  Here, the lower alkyl group represented by R is not limited, but can be a normal or branched alkyl group having 1 to 6 carbon atoms. Specifically, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, ter-butyl group, pentyl group, 1,2-dimethylpropyl group, 1, 1-dimethylpropyl group, 2,2-dimethylpropyl group, 2-ethylpropyl group, n-hexyl group, 1,2-dimethylbutyl group, 2,3-dimethylbutyl group, 1,3-dimethylbutyl group, 1 -Ethyl-2-methylpropyl group, 1-methyl-2-ethylpropyl group and the like can be mentioned. Preferably it is a C1-C4 linear or branched alkyl group, More preferably, it is a methyl group.

  Specific examples of the compound (1) include xanthoangelol in which R is a hydrogen atom and n is 2, and 4-hydroxyderricin in which R is a methyl group and n is 1. it can.

  These compounds may be either free or salt forms. Examples of the salt include a pharmaceutically acceptable salt, for example, a salt with an inorganic base or an organic base, or an acid addition salt such as an inorganic acid, an organic acid, or a basic or acidic amino acid. Examples of the inorganic base include alkali metals such as sodium and potassium; alkaline earth metals such as calcium and magnesium; aluminum and ammonium. Examples of the organic base include primary amines such as ethanolamine; secondary amines such as diethylamine, diethanolamine, dicyclohexylamine, N, N′-dibenzylethylenediamine; trimethylamine, triethylamine, pyridine, picoline, triethanolamine and the like. And tertiary amines.

  Examples of inorganic acids that form acid addition salts include hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like. Examples of organic acids include formic acid, acetic acid, lactic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, benzoic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, ethanesulfonic acid, and benzenesulfone. An acid, p-toluenesulfonic acid, etc. can be mentioned. Examples of basic amino acids include arginine, lysine, ornithine and the like. Examples of acidic amino acids include aspartic acid and glutamic acid.

  In addition, monosaccharides, oligosaccharides, sugar alcohols, and the like may be glycosylated with these compounds in order to increase solubility, stability, and enhance physiologically active functions. The number of preferable sugars is 1-20, and glucose, galactose, mannose, fructose, maltose, sucrose, etc. can be mentioned.

  The plaque formation inhibitor or anti-cariogenic agent of the present invention only needs to contain the compound (1) or a salt thereof as an active ingredient, and the purity of the compound (1) to be blended is not particularly limited. For example, as a roughly purified product of compound (1), a plant component containing compound (1) or a salt thereof or a processed product thereof may be included regardless of the degree of purification. Here, the plant component means a liquid contained in a plant such as the plant itself or sap, and the processed product refers to a whole plant or a part of the plant, or a liquid contained in the plant (for example, sap). It means what has been subjected to treatment (drying, extraction, squeezing, heating, purification treatment, etc.).

  Although the kind of plant will not be restrict | limited especially if a compound (1) or its salt is included, Tomorrow leaves can be mentioned preferably. Tomorrow is a celery family plant with the scientific name "Angelica keiskei koidz." Native to warm regions such as Hachijojima and Izu Islands. In recent years, tomorrow leaves using Hachijojima seeds are cultivated not only in Japan but also in various regions such as Indonesia and Korea. The origin of tomorrow used in the present invention is not particularly limited.

  As for tomorrow leaves, whole plants may be used, or some of them (for example, roots, stems, leaves, fruits (seed), florets, flowers, bark, etc.) may be used. Such a site for tomorrow can be used without particular limitation as long as it is a site having a plaque formation-inhibiting action or an anti-cariogenic effect (a site containing compound (1) or a salt thereof). Preferred examples include sap of tomorrow leaves, roots and stems of tomorrow leaves.

  Since the sap exudes from the wound or cut surface by scratching or cutting plant tissues (for example, leaves, stems, roots, etc.), the exudate can be collected and used. . It is also possible to collect the sap with water or a solvent after crushing the whole plant of tomorrow or part thereof.

  The whole plant of tomorrow or a part thereof, or the sap of tomorrow can be used as it is, but it is usually used in a state subjected to arbitrary processing (pulverization, drying, concentration, extraction, etc.). For example, concentration or solvent extraction can be preferably used for the sap of tomorrow leaves, and solvent extraction can be preferably used for the whole plant of tomorrow leaves or a part thereof (for example, roots and stems).

  In the solvent extraction, the whole plant of tomorrow or a part thereof may be used as it is or as a crushed product thereof, or may be subjected to an extraction operation after crushing as necessary after drying. Further, the sap of tomorrow leaves may be subjected to the extraction operation as it is, or may be subjected to the extraction operation after being concentrated or dried and crushed as necessary.

  The solvent used for the extraction is not particularly limited as long as it is a solvent capable of extracting a component (compound (1) or a salt thereof) having a plaque formation-inhibiting action or an anti-cariogenic action. Fats and oils such as alcohol and essential oils, nonpolar and polar solvents, and supercritical or subsupercritical fluids can be widely used. More specifically, examples of the lower alcohol include alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropyl alcohol, and butanol; examples of the polyhydric alcohol include glycerin and polyethylene glycol; examples of the nonpolar solvent include pentane, Saturated hydrocarbons such as hexane, heptane, octane, nonane, decane, etc. or unsaturated hydrocarbons such as hexene, heptene, etc .; polar solvents include acetone, ethyl acetate, methyl acetate, etc .; supercritical or subsupercritical fluids such as dioxide Carbon, ethane, ethylene, etc. are used. These solvents may be used alone or in combination of two or more. For example, in the case of a raw material containing a large amount of fat, after performing a degreasing extraction treatment with a nonpolar solvent, the extraction treatment may be performed with any arbitrary solvent, or the extraction treatment may be performed using a water-containing organic solvent. Preferred is a lower alcohol, particularly ethanol. The lower alcohol can also be mixed with water and used as a hydrous alcohol (preferably hydrous ethanol). Examples of the alcohol concentration in this case include 1 to 99.9% by volume. Preferably it is 70 volume% or more.

  As the extraction method, a generally used method can be employed. Although not limited, for example, a method of immersing tomorrow's sap or whole grass or part (as it is or crude powder, shredded product) or a dried crushed material (powder etc.) in a solvent by cold immersion, digestion, etc. Examples include a method of performing extraction while heating and stirring and filtering to obtain an extract, a supercritical or subsupercritical extraction method using the above supercritical or subsupercritical extraction fluid, or a percolation method.

  The obtained extract may be used as it is or after partially removing or concentrating the solvent by distilling off the solvent, after removing solids by filtration or centrifugation as necessary. Also good. Further, after concentration or drying, the concentrated or dried product may be used after being purified by washing with an insoluble solvent, or may be further dissolved or suspended in an appropriate solvent. In addition, the extract may be fractionated (including compound (1) or a salt thereof) having a plaque formation-inhibiting action or an anti-cariogenic action by using a conventional purification method such as countercurrent distribution or liquid chromatography. It is also possible to obtain and purify the fraction). Furthermore, in the present invention, for example, the solvent extract obtained as described above can also be used as a dried tomorrow extract by ordinary means such as drying under reduced pressure or freeze drying.

  The solvent extract or tomorrow leaf sap thus obtained exhibits an excellent plaque formation inhibitory action and a growth inhibitory action (anti-cariogenic action) against carious bacteria. Alternatively, it can be used as an anti-cariogenic agent, but if desired, it may be formulated by blending components such as optional auxiliaries and excipients according to a conventional method. In addition, as described later, as an active ingredient of various oral compositions (quasi-drugs, pharmaceuticals, cosmetics) and foods and drinks for preventing oral diseases such as caries and periodontal diseases, gingivitis and alveolar pus leakage It can also be used.

(2) Oral composition As described above, the plaque formation inhibitor or anti-cariogenic agent of the present invention can be used as an active ingredient of various oral compositions such as quasi drugs, pharmaceuticals, and cosmetics, Thus, by preventing the formation of plaque (plaque) in the oral cavity and suppressing the growth of caries bacteria, it effectively prevents oral diseases such as caries, periodontal disease, gingivitis and alveolar pus An oral composition having an effect can be prepared.

  In addition, in this invention, the composition for oral cavity means what is used in an oral cavity irrespective of the quasi-drug, a pharmaceutical, and cosmetics. Specifically, for example, dentifrice (kneaded, liquid, powdered), mouth spray, mouthwash such as mouthwash and mouth rinse, chewing agent, troche, pasta for oral cavity, gum massage cream, gargle And syrups. Preferable examples include mouthwashes, mouthwashes such as mouthwashes and mouth rinses. These forms and dosage forms are not particularly limited, and can be arbitrarily determined according to the type.

  The applied concentration of the plaque formation inhibitor or anti-cariogenic agent of the present invention is determined by various factors such as the type of oral composition, the proportion of active ingredients contained in the plaque formation inhibitor or anti-cariogenic agent, and the degree of dilution in the mouth. Can be selected and determined as appropriate. Although it does not restrict | limit in particular, As a concrete mixture ratio of the plaque formation inhibitor or anti-cariogenic agent mix | blended per 100 weight% of composition for oral cavity, it converts into the quantity of a compound (1), and is 0.001. -50 wt%, preferably 0.001-10 wt%, more preferably 0.005-1 wt%.

  In addition, when the plaque formation inhibitor or the anti-cariogenic agent contains a solvent extract or sap of tomorrow as an active ingredient, the plaque formation inhibitor or the anti-caries compounded per 100% by weight of the oral composition. As a specific blending ratio of the fungicide, 0.001 to 99.9% by weight, preferably 0.005 to 50% by weight is exemplified in terms of the amount of the solvent extract of tomorrow or the dried product of sap. be able to.

  As long as the composition for oral cavity of the present invention does not interfere with the effects of the present invention, as other components, an antibacterial agent for oral cavity such as a known plaque formation inhibitor, an antibacterial agent against Streptococcus mutans (an anti-cariogenic agent), A glucosyltransferase inhibitor, an anti-inflammatory agent, an animal or plant component, an animal or plant extract, or other ingredients used for oral preparations, inhalation sprays or gargles, etc. can also be combined. Moreover, the composition for oral cavity of this invention can be used together with the component normally mix | blended with this oral composition according to the kind of oral composition to apply.

  Examples of the plaque formation inhibitor include, but are not limited to, lytic enzymes such as fluorine, sodium fluoride, stannous fluoride, xylitol, palatinose, dextranase, mutanase, lysozyme chloride, and trehalulose. it can.

  The antibacterial agent for oral cavity is not limited, but cetylpyridinium chloride, 1,8-cineole, triclosan, hinokitiol, cefcapene hydrochloride, chlorhexidine hydrochloride, povidone iodine, acrinol, isopropylmethylphenol, chlorhexidine gluconate, creosote, thymol, hinokitiol, Phenol, benzethonium chloride, chlorhexidine, benzalkonium hydrochloride, and decalinium chloride can be exemplified.

  Examples of glucosyltransferase inhibitors include, but are not limited to, tea extract, catechin, epigallocatechin gallate (EGCG), and protoanthocyanidins.

  Animal and plant components or animal and plant extract extracts include herbal extracts, seaweed extracts, yeast extracts, tea extracts, Kumazasa extract, pearl powder (pearl powder), apple extracts, rose oil, marigold flower extract (Lutein), Propolis extract, Melon extract, Olive leaf extract, Mucuna extract, Rose petal extract, Hermapule extract powder, Cordyceps extract, Sage extract, Bodaiju extract, Hypericum extract, Enmeso extract, Lacanca extract, Ginseng extract, Bee Litter, noni extract, green papaya enzyme powder, white mushroom extract, grape seed extract, yucca extract, lychee seed extract, shiso leaf extract, shiso seed extract, tomato pigment extract, pomegranate extract, Chicken crown extract (containing hyaluronic acid and collagen), raspberry extract, duck Extract, star fruit extract, fenugreek extract, lotus germ extract, moon peach leaf extract, rice extract (containing ceramide), rice bran extract, hematococcus extract algae pigment (astaxanthin), black pepper extract, brewer's yeast (containing zinc) , Gelatin, beeswax, rosemary extract, ginkgo biloba extract, persimmon tea extract, soybean extract, soybean germ extract, water-soluble collagen, coenzyme Q10, coffee bean extract, turmeric extract, cherry extract, bilberry extract, Cassis extract, persimmon tannin extract, rooibos tea extract, apple fiber, mukuroji extract, licorice extract, maiko extract, psyllium husk powder (plantago obata which is a kind of plantain), gymnema sylvesta powder, guava leaf extract, chromium Yeast, barley young leaf powder, and crab Powder can be exemplified.

  Other ingredients used in oral preparations, inhalation sprays, or mouthwashes include acetylsalicylic acid, ethyl aminobenzoate, ethanol, ether, sodium chloride, epilocaine hydrochloride, ephedrine hydrochloride, potassium chlorate, eugenol, Chamomile, ginseng, licorice, camphor, quill, guaiazulene, sodium guaiazulenesulfonate, dipotassium glycyrrhizinate, β-glycyrrhetinic acid, chloropheniramine, chlorophyllin, phenyl salicylate, methyl salicylate, sicon, dibucaine, silver nitrate, sulfadiazine, Senega, sodium bicarbonate, magnesium carbonate, clove, tetradecylaminoethylglycine, copper chlorophyllin sodium, dodecyldiaminoethylglycine, carrot, honey, honey, Procaine, diethylaminoethyl 2-hexoxy-4-aminothiobenzoate, homosulfamine, chlorpheniramine maleate, myrrh, menthol, eucalyptus oil, potassium iodide, iodine, iodoglycerin, aluminum potassium sulfate, lidocaine, liuouno, sorbic acid, Examples include alexidine, alkyl glycine, alkyl diaminoethyl glycine salt, sodium monofluorophosphate, water-soluble primary or secondary phosphate, quaternary ammonium compounds, and components having similar pharmacological action.

  More specifically, for example, in the case of a toothpaste, as a component that can be blended, abrasives such as dicalcium phosphate, calcium carbonate, insoluble sodium metaphosphate, amorphous silica, aluminum oxide; carboxymethylcellulose, hydroxyethylcellulose, alginate Binders such as carrageenan, gum arabic, and polyvinyl alcohol; thickeners such as polyethylene glycol, sorbitol, glycerin, propylene glycol; sodium lauryl sulfate, sodium dodecylbenzenesulfonate, hydrogenated coconut fatty acid monoglyceride sodium monosulfate, Examples include foaming agents such as sodium lauryl sulfoacetate, sodium N-lauroyl sarcosinate, N-acyl glutamate, sucrose fatty acid ester, and the like. Perfumes and flavoring agents or sweetening agents, such as menthol, can be blended a preservative or the like.

  In the case of mouthwashes such as mouthwash and mouth rinse, conventional ingredients can be blended. In addition, as a sweetening agent mix | blended together, what has low or no caries property is preferable, For example, D-xylose, a xylitol, a saccharin sodium, aspartame, a trehalose etc. can be mentioned suitably.

(3) Food and drink The plaque formation inhibitor or anti-cariogenic agent of the present invention described above can be used as an active ingredient of food and drink for the purpose of preventing caries, periodontal disease, etc. A food and drink having an effect of effectively preventing oral diseases such as caries, periodontal disease, gingivitis and alveolar pus leakage by preventing plaque formation and inhibiting the growth of caries bacteria Can be prepared.

  Food and drinks are not limited here, but preferably troches, chewing gums, candies (hard, soft), gummy candies, etc .; chocolates; desserts such as jelly, yogurt, pudding; baked goods such as cookies and cakes Bread; Tablets; Frozen foods; Noodles; Juice and soft drinks; Beverages such as soups.

  The applied concentration of the plaque formation inhibitor or anti-cariogenic agent is appropriately determined in consideration of various factors such as the type of food and drink, the proportion of active ingredients contained in the plaque formation inhibitor or anti-cariogenic agent, and the degree of dilution in the mouth. Selection can be determined. Although it does not restrict | limit in particular, As a concrete mixture ratio of the plaque formation inhibitor or anti-cariogenic agent mix | blended per 100 weight% of food-drinks, it converts into the quantity of a compound (1), and is 0.001-50. % By weight, preferably 0.001 to 10% by weight, more preferably 0.005 to 1% by weight.

  In addition, when the plaque formation inhibitor or anti-cariogenic agent contains a solvent extract or sap of tomorrow as an active ingredient, the plaque formation inhibitor or anti-cariogenic agent added per 100% by weight of food or drink As a specific blending ratio, 0.001 to 99.9% by weight, preferably 0.005 to 50% by weight, may be exemplified in terms of the amount of the solvent extract of tomorrow or the dried product of sap. it can.

  As long as the effects of the present invention are not hindered, the food and drink of the present invention include, as other components, oral antibacterial agents such as known plaque formation inhibitors, antibacterial agents (anti-cariogenic agents) against Streptococcus mutans, glucosyltransferase inhibition It can also be blended in combination with an agent, or an animal or plant component, an animal or plant extract. Moreover, the food / beverage of this invention can be used together with the component normally mix | blended with the said food / beverage depending on the kind of food / beverage. For example, as a sweetening agent used in combination, those having low or no caries are preferable, and examples thereof include D-xylose, xylitol, sodium saccharin, aspartame, trehalose and the like.

Hereinafter, the present invention will be specifically described with reference to Preparation Examples, Test Examples, and Formulation Examples, but the present invention is not limited to the following examples. In the following preparation examples, “95 volume% aqueous ethanol” means an aqueous solution containing ethanol at a ratio of 95 volume%.
<Preparation example>
Production Example 1 Tomorrow Leaf Sap Concentrate Commercial tomorrow leaf sap (50 g) was placed in an eggplant flask and vacuum concentrated with an evaporator to obtain tomorrow leaf sap concentrate (4 g). This concentrate was accurately weighed and dissolved in DMSO (Dimethyl Sulfoxide) so as to be 5 mg / mL and 10 mg / mL.

Production Example 2 95 vol% ethanol-containing ethanol extract of tomorrow leaf sap A commercially available tomorrow leaf sap (100 g) was placed in an eggplant flask and vacuum concentrated with an evaporator to obtain an tomorrow leaf sap concentrate. This concentrate is dissolved in 5 volumes of 95% by volume hydrous ethanol, heated to remove insoluble matter with No. 2 filter paper, and then concentrated in vacuo using an evaporator, and the 95% by volume hydrous ethanol extract of tomorrow's leaf tree sap ( 95% by volume water-soluble ethanol soluble material) (22 g) was obtained. This was accurately weighed and dissolved in DMSO to 5 mg / mL and 10 mg / mL.

Production Example 3 Water extract of tomorrow leaf sap Commercial tomorrow leaf sap (50 g) was placed in a separatory funnel, and the same amount of ethyl acetate was added to perform liquid-liquid partition. After repeating this operation (liquid-liquid distribution) three times for the aqueous layer, the recovered water tank was vacuum concentrated with an evaporator to obtain a water extract concentrate (water soluble) (1.8 g) of tomorrow leaf tree sap. It was. This was accurately weighed and dissolved in DMSO to 5 mg / mL and 10 mg / mL.

Production Example 4 Root extract of tomorrow leaves Fresh tomato roots (1 kg) were pulverized and extracted for 1 hour at room temperature with 3 volumes of 95% aqueous ethanol. The pulverized product (extraction residue) of tomorrow leaves after extraction was extracted again for 1 hour at room temperature with 3 volumes of 95% aqueous ethanol. This operation was performed 3 times in total. The obtained extracts were combined and concentrated in vacuo with an evaporator to obtain a concentrate (89 g) of tomorrow leaf root extract. This was accurately weighed and dissolved in DMSO to 5 mg / mL and 10 mg / mL.

Production Example 5 Stem extract of tomorrow leaves Fresh tomato stems (790 g) were pulverized and extracted for 1 hour at room temperature using 3 volumes of 95 vol% aqueous ethanol. The pulverized product (extraction residue) of tomorrow's stem after extraction was extracted again for 1 hour at room temperature with 3 volumes of 95% aqueous ethanol. This operation was performed 3 times in total. The obtained extracts were combined and concentrated in vacuo with an evaporator to obtain a concentrate (49 g) of tomorrow leaf stem extract. This was accurately weighed and dissolved in DMSO to 5 mg / mL and 10 mg / mL.

Production Example 6 Leaf extract of tomorrow leaves Fresh tomato leaves (500 g) were pulverized and extracted for 1 hour at room temperature with 3 volumes of 95% ethanol in water. The pulverized product (extraction residue) of tomorrow leaves after extraction was extracted again with 3 volumes of 95% by volume aqueous ethanol at room temperature for 1 hour. This operation was performed 3 times in total. The obtained extracts were combined and concentrated under vacuum using an evaporator to obtain a leaf extract concentrate (72 g). This was accurately weighed and dissolved in DMSO to 5 mg / mL and 10 mg / mL.

Production Example 7 Flower extract of tomorrow leaves Fresh tomato leaves flowers (190 g) were pulverized and extracted for 1 hour at room temperature with 3 volumes of 95% ethanol in water. Extraction of tomorrow's flower pulverized product (extraction residue) after extraction was performed again at room temperature for 1 hour using 3 volumes of ethanol containing 95% by volume. This operation was performed 3 times in total. The obtained extract was vacuum concentrated with an evaporator to obtain a concentrate (12 g) of tomorrow leaf flower extract. This was accurately weighed and dissolved in DMSO to 5 mg / mL and 10 mg / mL.

Production Example 8 Isolation and purification of 4-hydroxyderricin and xanthoangelol (1) An ethanol-solubilized product (22 g) extracted from tomorrow leaf sap with 95 vol% aqueous ethanol was applied to a silica gel column, and CHL ₃ was used as the eluent. Elution with a mixed solvent of EtOAc (20: 1) and fractionation into each fraction. From the fractionated fraction, while confirming both yellow components using TLC, the 4-hydroxyderricin-containing fraction and the xanthoangelol-containing fraction were selected, and the resulting 4-hydroxyderricin-containing fraction and xanthone were obtained. Toangelol-containing fractions were concentrated. Further, each fraction concentrate was repeatedly purified on a gel filtration column (Sephadex LH20, 200 mL) (eluent: 90% by volume aqueous methanol) and silica gel column (eluent: CHL ₃ : EtOAc = 20: 1), A pure product of 4-hydroxyderricin (2.9 g) and xanthoangelol (1 g) was obtained.

4-hydroxyderricin and xanthoangelol were subjected to ¹ H-NMR spectrum and ¹³ C-NMR spectrum, respectively, and the obtained pure product was 4-hydroxyderricin represented by the following formula (2):

  And xanthoangelol represented by the following formula (3)

It was confirmed that.

Purified 4-Hydroxyderricin (4-hydroxyderricin) and Xanthoangelol (xanthoangelol) were measured and confirmed using a JNM-ECA600 NMR apparatus. Results of ¹ H- NMR and ¹³ C-NMR of 4-hydroxy deli thin, and the results of ¹ H- NMR and ¹³ C-NMR of xanthoangelol below.

(1) of 4-hydroxyderricin ¹ H-NMR and ¹³ C-NMR

(2) Xanthoangelol ¹ H-NMR and ¹³ C-NMR

(2) 4-Hydroxyderricin 4-Hydroxyderricin prepared above was precisely weighed and dissolved in DMSO to give 5 mg / mL and 10 mg / mL.

(3) Xanthoangelol Xanthoangelol prepared above was precisely weighed and dissolved in DMSO to give 5 mg / mL and 10 mg / mL.

<Test example>
Test Example 1 Plaque Production Inhibitory Action The following samples 1 to 9 prepared in Production Examples 1 to 8 and the following samples 10 to 12 as positive controls were evaluated for plaque production inhibitory action according to the following method. In addition, as a control, the same test was conducted without adding any sample, and the plaque formation inhibitory action was evaluated.

(1) Sample Sample 1: Tomorrow leaf sap Sample 2: 95 vol% aqueous ethanol extract of tomorrow leaf sap Sample 3: Water extract of tomorrow leaf sap Sample 4: 95 vol% aqueous ethanol extract of tomorrow leaf sap Sample 5 : 95% by volume aqueous ethanol extract of tomorrow leaves Sample 6: 95% by volume aqueous ethanol extract of tomorrow leaves Sample 7: 95% by volume aqueous ethanol extract of tomorrow leaves Sample 8: 4-hydroxyderricin ( 4-hydroxyderricin)
Sample 9: xanthoangelol
Sample 10: Thymol Sample 11: Cetylpyridinium chloride Sample 12: Epigallocatechin gallate Control control: No sample added.

(2) Test method Streptococcus mutans (GTC218) was incubated in a BHI broth (Brain-Heart Infusion broth) liquid medium at 37 ° C. for 48 hours, and this was diluted 1000 times (approximately 10 ⁴ cells / mL). A fungal stock solution was prepared. Put 2.4 mL of BHI medium in a sterilized test tube, add each sample sterilized by filtration with a 0.45 μm filter to a final concentration of 50 or 100 μg / mL, and mix 50 μL of the bacterial stock solution. Finally, sucrose is added to 1% and anaerobic culture is performed at 37 ° C. for 48 hours. Thereafter, the culture solution is gently removed, washed with distilled water and acetone, vacuum-dried, and the weight of the plaque adhering to the smooth glass surface is measured.

  The result which shows the presence or absence of the production | generation of a plaque by addition of each sample is shown in FIG. Moreover, the result of having calculated | required the plaque production | generation suppression rate (%) by the following formula from the weight of the plaque obtained above is shown in FIG. 2 (A is a result of a sample 50 μg / mL, and B is a result of a sample 100 μg / mL).

  From this result, it can be seen that the sap of tomorrow leaves, its 95% by volume aqueous ethanol extract, and the 95% by volume aqueous ethanol extract of tomorrow's root have an excellent plaque formation inhibitory action comparable to cetylpyridinium chloride. It was. In addition, since 4-hydroxyderricin and xanthoangelol isolated and purified by extraction with water-containing ethanol from tomorrow's sap were also found to have a strong plaque formation inhibitory effect, the above-mentioned inhibition of plaque formation in tomorrow's leaves was observed. The active ingredient of action is considered to be 4-hydroxyderricin or xanthoangelol.

Test Example 2 S. mutans growth inhibitory action In the same manner as described above, samples 1 to 9 prepared in Production Examples 1 to 8 and samples 10 to 12 as a positive control were tested for caries bacteria according to the following method. The growth inhibitory action was evaluated. As a control, the same test was conducted with no sample added to evaluate the growth inhibitory effect of caries.

(1) Test method Streptococcus mutans (GTC218) was incubated in a BHI broth (Brain-Heart Infusion broth) liquid medium at 37 ° C. for 48 hours, and this was diluted 1000 times (approximately 10 ⁴ cells / mL). A fungal stock solution was prepared. 4.9 mL of BHI medium is put in a sterilized test tube, and each sample sterilized by filtration with a 0.45 μm filter is added to a final concentration of 50, 100, 200 μg / mL, and 100 μL of the bacterial stock solution is further added. Mix and incubate at 37 ° C for 24 hours. Thereafter, the growth of the bacteria is measured at a turbidity of 600 nm. FIG. 3 shows the results of obtaining the caries growth inhibition rate (%) from the obtained 600 nm turbidity by the following formula.

  From this result, the sap of tomorrow leaves, its 95 volume% aqueous ethanol extract, the 95 volume% aqueous ethanol extract of tomorrow root, and the 95 volume% aqueous ethanol extract of tomorrow leaf stem are cetylpyridinium chloride and It was found that it has an anti-cariogenic action (an inhibitory action on the growth of carious bacteria) that is superior to thymol. It should be noted that 4-hydroxyderricin and xanthoangelol isolated and purified by extraction with water-containing ethanol from tomorrow's sap also have strong anti-cariogenic activity (caries bacteria growth inhibitory activity), Since the action was not recognized in the water-soluble matter of tomorrow, the active ingredient of the tomorrow's anti-cariogenic action (caries bacteria growth-inhibiting action) is 4-hydroxyderricin or xanthoane. It is considered to be gerol.

Test Example 3 Minimum Growth Inhibitory Concentration of Cariogenic Bacteria (S. mutans) For Samples 1 to 9 prepared in Production Examples 1 to 8 and Samples 10 to 12 as positive controls in the same manner as described above, according to the paper disk method shown below The minimum inhibitory concentration of cariogenic bacteria was measured. As a control, the same test was carried out with no sample added to determine the minimum inhibitory concentration of caries.

(1) Test method Streptococcus mutans (GTC218) is pre-cultured in a BHI broth (Brain-Heart Infusion broth) liquid medium (microbio), and 400 μL of this pre-culture solution is applied to a BHI agar medium (Eiken Chemical). did. A paper disk (ADVANTEC TOYO PAPERDISK Thick, diameter 8 mm) impregnated with 50 μL of each sample (final concentration 25, 50, 100, 200 μg / mL) sterilized by filtration with a 0.45 μm filter was left on the surface of the agar medium. Then, thymol, cetylpyridium chloride (CPC), and epigallocatechin gallate (EGCG) were used as control drugs, and caries bacteria (S. mutans) were anaerobically cultured at 37 ° C. for 3 days. Antibacterial activity was evaluated from the growth inhibition circle around the paper disk.

  The results are shown in Table 3.

[Formulation Example 1]
The following raw materials were processed by a conventional method of toothpaste production to produce a toothpaste that is a kind of oral composition.
Tomorrow leaf sap concentrate (Production Example 1) 0.1 (g)
Calcium carbonate 35.0
Sorbitol 20.0
Carboxymethylcellulose 1.0
Sodium lauryl sulfate 1.0
Saccharin 0.1
Fragrance 1.0
Allantoin 0.01
Dipotassium glycyrrhizinate 0.01
The remainder of purified water (the total amount is 100 g).

[Formulation Example 1]
The following raw materials were processed by a conventional method for producing a mouth freshener to produce a mouth freshener, which is a kind of oral composition.
Tomorrow leaf sap extract (Production Example 2) 0.05 (g)
l-Menthol 0.1
Peppermint oil 0.1
Polyglycerin fatty acid ester 4.0
Ethanol 45.0
Saccharin sodium 0.01
pH adjusting agent
The remainder of purified water (the total amount is 100 g).

[Composition Example 3]
Candy was produced according to a conventional method using the following raw materials.
Tomorrow leaf sap concentrate (Production Example 1) 0.05 (g)
Granulated sugar 45.0
Enzymatic saccharified starch syrup 43.0
Cyclodextrin 0.6
Fragrance 0.1
Azulene 0.1
The remainder of the water (the total amount is 100 g).

[Formulation Example 4]
A chewing gum was produced according to a conventional method using the following raw materials.
Tomorrow leaf sap concentrate (Production Example 1) 0.5 (g)
Chewing gum base 24.0
Granulated sugar 55.3
Minamata 15.0
Softener 5.0
Chlorophyll 0.1
Fragrance 0.1
Total 100.0g.

It is an image which shows the result of the presence or absence of plaque generation in Test Example 1. From left to right: 1: control (no sample added), 2: sample 1 (tomorrow leaf sap), 3: sample 2 (95% aqueous ethanol extract of tomorrow leaf sap), 4: sample 3 (tomorrow leaf sap) 5: Sample 4 (95% by volume aqueous ethanol extract of tomorrow leaf root), 6: Sample 5 (95% by volume aqueous ethanol extract of tomorrow leaf), 7: Sample 6 (tomorrow leaf stem) 95% water-containing ethanol extract), 8: sample 7 (95% water-containing ethanol extract of tomorrow leaf flower), 9: sample 8 (4-hydroxyderricin), 10: sample 9 (xanthoangelol) 11: Sample 10 (thymol), 12: Sample 11 (cetylpyridinium chloride), 13: Sample 12 (epigallocatechin gallate). The result of having calculated | required the plaque production | generation suppression rate (%) in the test example 1 is shown. The result of having calculated | required the caries bacteria growth inhibition rate (%) in the test example 2 is shown.

Claims (10)

General formula (1)

(In the formula, R represents a hydrogen atom or a lower alkyl group, and n represents 1 or 2.)
The plaque formation inhibitor which contains the compound shown by these, or its salt as an active ingredient.   The plaque formation inhibitor of Claim 1 containing the plant component containing the compound (1) or its salt, or its processed material.   The plant component or processed product thereof is any one selected from the group consisting of a solvent extract of tomorrow leaf roots, stems and sap, tomorrow leaf sap, and a concentrate of tomorrow leaf sap. Plaque formation inhibitor. General formula (1)

(In the formula, R represents a hydrogen atom or a lower alkyl group, and n represents 1 or 2.)
An anti-cariogenic agent comprising the compound represented by the above or a salt thereof as an active ingredient.   The anti-cariogenic agent according to claim 4, comprising a plant component containing the compound (1) or a salt thereof or a processed product thereof.   The plant component or processed product thereof is any one selected from the group consisting of a solvent extract of tomorrow leaf roots, stems and sap, tomorrow leaf sap, and a concentrate of tomorrow leaf sap. Anti-cariogenic agent.   Containing at least one selected from the group consisting of the plaque formation inhibitor according to claims 1 to 3 and the anti-cariogenic agent according to claims 4 to 6 as an active ingredient for prevention of dental caries or oral disease. An oral composition characterized by the above.   The composition for oral cavity for preventing a dental caries or an oral disease at least one chosen from the group which consists of the plaque formation inhibitor described in Claims 1-3, and the anti-cariogenic agent described in Claims 4-6. The method used to manufacture.   Containing at least one selected from the group consisting of the plaque formation inhibitor according to claims 1 to 3 and the anti-cariogenic agent according to claims 4 to 6 as an active ingredient for prevention of dental caries or oral disease. Food and drink characterized by   Manufacturing at least one selected from the group consisting of the plaque formation inhibitor described in claims 1 to 3 and the anti-cariogenic agent described in claims 4 to 6 for preventing caries or oral disease. How to use to

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