JPH0881380A - Anti-periodontitis agent and anti-periodontitis food containing high-molecular weight polyphenol as active component - Google Patents

Abstract

PURPOSE: To provide a high-molecular weight polyphenol capable of preventing generation and proceeding of periodontitis by inhibiting adhesion of Porphyromonas gingivalis as a causing molds of periodontitis to periodontium. CONSTITUTION: This anti-periodontitis agent contains polyphenol having a weight-averaged molecular weight of 800-10,000 and a degree of polymerization of 3-30 derived from trees, fermented tea or a plant belonging to Rosaceae Pyracantha, etc. Said polyphenol itself has no special taste nor smell and therefore the anti-periodontitis agent containing the polyphenol as an active component is widely usable for preventing periodontitis as a sanitary agent for oral cavity or an additive for food.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an anti-periodontal disease agent containing a polyphenol having an action of inhibiting adhesion of periodontal disease-causing bacteria as an active ingredient, and more specifically, to heartwood and bark of trees, fermented tea leaves or roses. Derived from plants such as Pyracantha spp., An anti-periodontal disease agent and an anti-periodontal disease food containing the polyphenol having an active ingredient of a polyphenol having an action of inhibiting adhesion of periodontal disease-causing bacteria, and the polyphenol It relates to a manufacturing method.

[0002]

2. Description of the Related Art Periodontal disease, which is generally called alveolar pyorrhea, is a typical dental disease along with caries (cavities). This disease is a chronic inflammation that occurs in the tissues that support the teeth and is an oral disease that involves periodontal tissue destruction. The symptom is generally gingival inflammation (gingivitis), followed by periodontal ligament. , Inflammation spreads to periodontal tissues such as alveolar bone, and eventually the teeth fall out.

The morbidity rate of periodontal disease tends to increase from the late twenties, and it is said that about 80% of middle-aged and elderly people are periodontal disease patients. Therefore, prevention of periodontal disease is a very important issue for modern people.

Although no clear knowledge has been obtained for a long time to explain the etiology and pathogenesis of the periodontal disease and the mechanism of its progress, a causal relationship with anaerobic Gram-negative bacteria has been gradually proposed. Among them, it is currently supported by many studies that Porphyromonas gingivalis (hereinafter referred to as “P. gingivalis”, formerly known as Bacteroides gingivalis) is a causative bacterium of periodontal disease. P. gingivalis is a microorganism that is frequently detected in the lesions of periodontitis patients, produces a tissue-destructive protease, has endotoxin, and promotes complement activation and leukocyte migration. It is a microorganism.

As a therapeutic agent for periodontal disease, a therapeutic agent for periodontal disease containing one or more selected from adenosine triphosphatase inhibitor, cysteine proteinase inhibitor, serine proteinase inhibitor and protein kinase C inhibitor has been already reported. (JP-A-5-97708).

[0006] However, in the above report, the activity is evaluated using inhibition of bone resorption of the mouse skull as an index, and it cannot be said that a sufficient anti-periodontal disease effect has been confirmed.

[0007]

As described above, the prevention of periodontal disease is a very important issue for modern people, but the present situation is that no preventive method for periodontal disease having a satisfactory effect has been found yet. Therefore, the development of an anti-periodontal disease agent that has a sufficiently strong effect and does not cause any problems with respect to the human body in terms of safety has been a problem.

[0008]

[Means for Solving the Problems] In order to obtain an effective anti-periodontal disease drug, the present inventors first examined the mechanism of the occurrence of periodontal disease. As a result, P. gingivalis showed gingival epithelial cells,
In particular, extracellular matrix (ECM, such as laminin, collagen, fibronectin, etc.) is attached as a target (Infection), and then tissue destructive enzymes (protease, collagenase), bacterial endotoxin, peptidoglycan, mediators such as teichoic acid ( The mechanism by which the release of lysosome-derived autolytic enzyme and the immune response reaction involving the recruitment of macrophages are caused by destruction of gingival tissue and inflammation, leading to the development of periodontal disease, has been clarified. .

In the above mechanism, a trypsin-like protease produced by P. gingivalis is regarded as important as a virulence factor, and it is involved in tissue destruction around the infected local area, facilitation of tissue entry of bacteria, and inflammatory effect. It is presumed that P. gingivalis is a fimbriae constituent protein called fimbriae when P. gingivalis attaches to gingival epithelial cells, and it was also clarified that the increased attachment of fimbria is a phenomenon dependent on the protease. It was

Further, it is presumed that the trypsin-like protease decomposes extracellular matrix such as laminin, collagen and fibronectin to induce the attachment of fimbriae to the gingival epithelial cells and the establishment of P. gingivalis to the periodontal tissue. Was done.

[0011] Therefore, based on the above-mentioned mechanism of periodontal disease, the present inventors have found that P. gingivalis, which is considered to be the first step in the development of periodontal disease, adheres to the periodontal tissue (Infecti).
on) was determined to be an important target for the prevention of periodontal disease, and an intensive study was conducted to find a substance that effectively suppresses the adhesion of P. gingivalis and has no harmful effect on the human body.

[0012] As a result, a group of plant-derived high-molecular-weight polyphenols such as polyphenols derived from acacia bark, wattle tannin, quebracotannin, or polyphenols derived from fermented tea leaves and plants of the genus Pyracantha of the family Rosaceae satisfy the requirements. As a result, they have completed the present invention.

That is, an object of the present invention is to provide an anti-periodontal disease agent containing a polyphenol having a weight average molecular weight of 800 to 10,000 and a degree of polymerization of 3 to 30 as an active ingredient. Another object of the present invention is to provide an anti-periodontal food containing the above polyphenol.
Still another object of the present invention is characterized by subjecting a plant such as a heartwood or bark of trees or fermented tea leaves or plants of the genus Pyracantha of the family Rosaceae to solvent extraction, and subjecting the extract to adsorption column chromatography. Another object of the present invention is to provide a method for producing an anti-periodontal disease-causing substance having an action of inhibiting adhesion of periodontal disease-causing bacteria.

The active ingredient of the anti-periodontal disease drug of the present invention has a weight average molecular weight of 800 to 10,000 and a degree of polymerization of 3 to 3.
Polyphenol of 0 (hereinafter sometimes referred to as “high molecular weight polyphenol”) can be obtained as a polyphenol derived from these by extracting plants such as trees, fermented tea leaves, and plants belonging to the genus Pyracanta. It is possible.

As the high molecular weight polyphenol derived from a tree, an extract itself of a heartwood or bark of a tree may be used, or a product purified from the extract may be used.
Further, kebraco tannin or wattle tannin, which is commercially available as a tree-derived polyphenol, may be used. Here, the kebraco tannins are the sumacaceae plants Schinopsis lorentzii Engl. And Schinopsis bala.
Tanse of heartwood such as nse Engl. Wattle tannin is tannin of bark of the legume Acacia molissima.

[0016] When obtaining a high-molecular weight polyphenol derived from a tree, the tree as an extraction raw material is not particularly limited, but preferred are sumacaceae (Anacardacea)), pinaceae (Pinaceae), legume (Leguminosae). Heartwood or bark of the tree, more preferred is Akashiya bark,
For example, larch bark. In addition, cinnamon bark, camphor bark, toothpick bark, quinch bark, sharbaim bark, barley bark and the like may be used as the extraction raw material.

On the other hand, as an extraction raw material for obtaining a high molecular weight polyphenol derived from fermented tea leaves, oolong tea,
Any fermented tea such as black tea or puar tea can be used. In addition, as a plant used to obtain a high molecular weight polyphenol derived from a plant belonging to the genus Pyracantha, the Chinese name “Pyracantha fortuneana” and Pyracantha angustifolia are preferable, and those fruits are particularly preferable as an extraction raw material. It is suitable.
Furthermore, plants of plants other than the genus Pyracanta, for example, grape, apple, cowberry, rhubarb, hemp bird, mahuang, coconut palm,
Yomimi, Asenyaku, lotus fruits, etc. may be used as extraction raw materials.

The solvent for extracting the high molecular weight polyphenol from each of the above raw materials is not particularly limited,
Methanol, ethanol, acetone, ethyl acetate, water,
Hot water or a mixed solvent system of these can be used. The temperature of the solvent at the time of extraction is not particularly limited, but is preferably 5 ° C to the boiling point of the solvent or lower, particularly 15 to 35 ° C. Also, the extraction time is not particularly limited,
It is preferably within the range of 2 hours to 2 weeks, particularly within 2 days. In addition, it is more preferable to perform the extraction under light shielding.

Each of the above extracts and commercially available kebracotannin, wattle tannin and the like can be used as they are as active ingredients of the anti-periodontal disease agent of the present invention.
Further purification is preferable.

Examples of the purification means for high molecular weight polyphenols include adsorbent treatment methods using synthetic adsorbents and the like, and membrane separation methods using reverse osmosis membranes and ultrafiltration membranes. Among these, more preferable examples are , Sephadex LH-
20 (Pharmacia, USA), Diaion HP
Column chromatography using a synthetic adsorbent column such as -20 (manufactured by Mitsubishi Kasei), SepaBeads HP1MG (manufactured by Mitsubishi Kasei), Toyopearl HW40F (manufactured by Toyo Soda Kogyo) and the like can be mentioned.

In order to specifically purify using column chromatography, various high molecular weight polyphenol extracts, commercially available kebracotannin, wattle tannin and the like are added in a small amount of water, a solvent such as methanol or ethanol, or a mixed solvent thereof. It may be dissolved in water, adsorbed on the above synthetic adsorbent column, thoroughly washed with water, and eluted with a hydrophilic organic solvent such as ethanol, methanol, acetone or a mixed solvent thereof.

For the high molecular weight polyphenol used in the present invention, the average molecular weight [weight average molecular weight (Mw)] and the degree of polymerization can be calculated for each elution fraction obtained by the purification step. Specifically, after dissolving the high molecular weight polyphenol fraction in a solvent such as tetrahydrofuran, it is adsorbed on a column such as Shodex KF-802 and 804 (Showa Denko) and then eluted with the same solvent at 280 nm. taking measurement. By comparing this measured value with a calibration curve prepared using a polystyrene standard, the molecular weight distribution of the high molecular weight polyphenol is obtained, and the weight average molecular weight is calculated from this. The degree of polymerization is calculated by setting the molecular weight of one unit to 290 after calculating the molecular weight of the maximum contained molecular species of the high molecular weight polyphenol fraction.

The high molecular weight polyphenol which is an active ingredient of the anti-periodontal disease agent of the present invention has a weight average molecular weight of 800 to 10,000 and a degree of polymerization of 3 to 30 as described above, but is more preferable. The weight average molecular weight is 1,500.
˜6,000 and degree of polymerization 5-20.

The high molecular weight polyphenol of the present invention can be used in any form such as an extract, a concentrated product, a solvent-free dried product, regardless of whether the extract or the purified product thereof is used. Storability,
From the viewpoint of the safety of the organic solvent, it is preferable to use a dried product.

The anti-periodontal disease drug of the present invention is produced by using the high molecular weight polyphenol obtained as described above as an active ingredient and combining this with a known pharmaceutically acceptable carrier.

The anti-periodontal disease agent in the present invention is mainly used as an oral hygiene agent, and specific examples of its dosage form include:
Examples include toothpaste, mouthwash, troche and the like.

In the production of this oral hygiene agent, appropriate components usually used depending on the dosage form can be used, and examples thereof include calcium carbonate, dicalcium phosphate, silicic acid anhydride, magnesium carbonate, and the like. Glycerin, sorbitol, propylene glycol, polyethylene glycol, carboxymethyl cellulose, methyl cellulose, sodium alginate, carrageenan, carboxyvinyl polymer, sodium dioctyl sulfosuccinate, sodium lauryl sulfate, sodium dodecylbenzene sulfonate, butyl paraoxybenzoate, hinokitiol, allantoin, glycyrrhizin, Alcohol, gum arabic, starch, corn starch, sodium saccharin, stevioside, glucose, lactose, magnesium stearate, monophosphate In addition to um, dipotassium phosphate, menthol, eucalyptus oil, peppermint, spearmint, pigments, sodium fluoride, fluorides such as sodium monofluorophosphate, anti-inflammatory agents such as lysozyme chloride and azulene, sodium chloride, etc. The components usually used can be blended appropriately.

Further, the anti-periodontal disease agent of the present invention can be in a dosage form added to various foods for the purpose of anti-periodontal disease. Examples of foods to which the anti-periodontal disease agent can be added include tea drinks, fruit juice drinks, coffee drinks, carbonated drinks, lactic acid bacteria drinks, chewing gum, candy, caramel, chocolate, ice cream and the like.

In the production of the above-mentioned food, appropriate components usually used can be used depending on the kind thereof,
Examples of components used include glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol. , Sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin Bs, Examples include nicotinamide, calcium pantothenate, amino acids, calcium salts, dyes, flavors, preservatives and the like which are commonly used as food materials.

Since the high molecular weight polyphenol of the present invention is a natural product derived from trees, fermented tea, etc., there is no problem in terms of safety, but when the polyphenol of the present invention is incorporated into an oral preparation, etc. , In terms of color, fragrance, etc.
A concentration range of 0001 to 0.5% is preferred.

[0031]

The high-molecular-weight polyphenol of the present invention strongly inhibits the protease produced by P. gingivalis, which is a causative bacterium of periodontal disease, to extremely strongly suppress the attachment of the bacterium to the periodontal tissue. It exhibits a sufficient effect for prevention of periodontal disease. The adhesion inhibitory activity of P. gingivalis, which is a high molecular weight polyphenol, greatly depends on the molecular weight. For example, polyphenol having a weight average molecular weight of less than 800 has a weak adhesion inhibitory activity, and thus is practically useful as an anti-periodontal disease agent. hard.

[0032]

[Examples] Next, the present invention will be described with reference to Examples relating to a method for producing a high molecular weight polyphenol of the present invention, a method for purifying a highly active substance, a method for measuring a molecular weight, and an assay test of P. gingivalis adhesion inhibitory activity on periodontal tissues. The present invention will be described in more detail, but the present invention is not limited to these examples.

Example 1 Production Example of Tree-Derived High-Molecular Weight Polyphenol: Acacia Bark (A) and Larch Bark (K) 1 k Each as Raw Material
The pulverized product of g was extracted with 10 L of acetone-water (7: 3 v / v). The extraction was performed at 25 ° C. for 2 days, and this was filtered with a glass filter. The filtrate was concentrated under reduced pressure to obtain powder residues of 107 g and 210 g, respectively.

The extracts from the acacia bark and larch bark thus obtained, the commercially available wattle tannins and quebraco tannins, were purified as follows.
That is, 5 g of each extract or tannin was dissolved in 10 ml of water-ethanol (1: 1 v / v), and a column (φ of Sephadex LH-20 (manufactured by Pharmacia, USA) was used.
3 cm × 100 cm). After washing with 2 liters of water, 2 liters each of ethanol, methanol, and acetone were sequentially eluted, and the obtained fractions were concentrated under reduced pressure to obtain an ethanol elution fraction (EE), a methanol elution fraction (ME), The fraction eluted with acetone (AE) was used.

As a result, 0.75 g of the EE fraction (A-EE) of the acacia bark extract and 3.2% of the same ME fraction (A-ME) were extracted.
5 g, the same AE fraction (A-AE) 0.70 g, larch bark extract EE fraction (K-EE) 0.9 g, the same ME fraction (K-ME) 1.50 g, the same AE fraction (K-AE) 2.
25 g each was obtained.

The EE fraction (W-
EE) 0.25 g, the same ME fraction (W-ME) 2.90 g,
0.50 g of the same AE fraction (W-AE), 0.60 g of the EE fraction of Qebracotannin (Q-EE), and the same ME fraction (Q
-ME) 1.75 g, AE fraction (Q-AE) 0.90 g
Were obtained respectively.

Example 2 Production Example of High-Molecular Weight Polyphenol Derived from Fermented Tea: 100 g of oolong tea was placed in a 2 liter Erlenmeyer flask, and 50
1 liter of volume% ethanol was added, and the mixture was gently stirred every hour at room temperature for extraction for 3 hours. This was filtered through Celite, and the obtained filtrate was concentrated under reduced pressure to remove ethanol, water was added and freeze-dried to obtain 29.2 g of an extract.
With respect to black tea and puar tea, 30.4 g and 31.3 g of extracts were obtained in the same manner as above.

Sephadex LH-20 column chromatography was carried out on 5 g of the oolong tea extract in the same manner as in Example 1 to obtain an ethanol elution fraction (OTE-E).
E). 2.20 g, methanol elution fraction (OTE-ME)
0.90 g, acetone elution fraction (OTE-AE) 0.50
g respectively.

Example 3 Production example of high molecular weight polyphenol derived from fire thorns: 50 g of dried fruits of fire thorns were immersed in 500 ml of hot water at 90 ° C., boiled for 3 hours and then filtered, and the obtained extract was concentrated under reduced pressure. Then, it was freeze-dried to obtain 13.3 g of an extract. 5 g of this extract was treated in the same manner as in Example 1 with Sephadex LH-20.
Column chromatography was performed, and 1.70 g of ethanol elution fraction (fire spine-EE), 1.25 g of methanol elution fraction (fire spine-ME), acetone elution fraction (fire spine-AE).
0.55 g each was obtained.

Example 4 Measurement of average molecular weight of each high molecular weight polyphenol fraction: The weight average molecular weight (Mw) of each high molecular weight polyphenol fraction obtained in Examples 1 to 3 was measured by the following method. As the column, Shodex KF-802 and 804 (Showa Denko) were used. Samples are each sample 2
It was prepared by dissolving mg in 10 ml of tetrahydrofuran. This was adsorbed on the above column, eluted with tetrahydrofuran, and detected at 280 nm. The calibration curve was created using polystyrene standards.

Each sample was eluted and the weight average molecular weight (Mw) of each fraction was measured by a conventional method. The degree of polymerization (DP) of each fraction was calculated for the maximum contained molecular species showing the maximum peak. That is, after calculating the molecular weight from the calibration curve, the degree of polymerization (DP) was calculated by considering 1 unit 290. The results are summarized in Table 1.

[0042]

Example 5 Assay of Protease Inhibitory Activity and Adhesion Inhibitory Activity of Each Polyphenol Fraction: AP Inhibitory Activity against P. gingivalis Protease; (1) Preparation of Protease P. gingivalis strain 381 strain manufactured by Nissui Pharmaceutical Co., Ltd. Anaerobic culture was performed in 12 L of GAM broth medium at 37 ° C. for 65 hours. This was centrifuged for 10 minutes at 8000 rpm, and the collected bacterial cells were suspended in a phosphate buffer of pH 7.4 containing 1 mM CaCl ₂ and 0.2% Triton X-100 and ultrasonically disrupted. The mixture was centrifuged again at 8000 rpm for 10 minutes, and the obtained supernatant was dialyzed against a phosphate buffer solution containing 1 mM CaCl _{2 and} having a pH of 7.4. Then, the dialysate is treated with Ar
g-Sepharose, DEAE Sepharose, and hydroxyapatite were sequentially subjected to column chromatography to obtain a partially purified protease. This protease was subjected to the following tests.

(2) Measurement of Protease Inhibitory Activity A synthetic substrate benzoyl-arginine-paranitroanilide (L-BAPA, manufactured by Sigma, USA) was added at pH 7.5 containing 0.30 mM CaCl ₂ and 0.88 mM cysteine.
88 mM phosphate buffer solution, the decomposition activity of the protease for the synthetic substrate was reacted at 37 ° C. for 20 minutes, and then measured by the absorbance at 405 nm. The protease inhibitory activity of each polyphenol fraction was determined by adding an appropriate amount thereof to the reaction solution at the same time as the synthetic substrate, and its IC ₅₀ was determined by a conventional method.

Inhibitory activity against adherence of B. P. gingivalis-derived fimbriae to extracellular matrix; (1) Preparation of fimbriae P. gingivalis strain 381 in GAM broth medium 12L
Anaerobic culture was carried out at 37 ° C for 65 hours. After culturing, 25 ℃,
The cells were collected by centrifugation at 8000 rpm for 10 minutes. The cells were treated with 0.15 M NaCl and 10 mM Mg.
Suspended in 20 mM Tris-HCl buffer (pH 7.4) containing Cl ₂ and mechanically fibrillated (pili constituent protein) by pipetting while stirring with a stirrer at room temperature.
Were peeled from the cells. This suspension was centrifuged at 8000 rpm for 15 minutes at 25 ° C. to obtain a supernatant. The supernatant was saturated with ammonium sulfate to 40% to obtain a precipitate.

The 40% ammonium sulfate precipitate was dissolved in 20 mM Tris-HCl buffer (pH 8.0) and dialyzed against the same buffer. After dialysis, it was subjected to DEAE Sepharose column chromatography equilibrated with the same buffer, and gradient elution was performed with a NaCl concentration gradient of 0 to 0.5 M to obtain a fimbrier fraction. This fimbrier fraction was saturated with ammonium sulfate to 50% to obtain a precipitate, which was
After suspending in M Tris-HCl buffer (pH 7.4), it was dialyzed against the same buffer to obtain 50 mg of purified fimbriae.

(2) Assay of inhibitory activity against attachment of fimbriae to extracellular matrix The purified fimbriae prepared in the preceding section was biotinylated by a conventional method. First, each well of a 96-well multiplate was coated with collagen, which is one of extracellular matrix proteins. That is, collagen derived from human lung (manufactured by Elastin Products) was added to 20 mM 10 mM acetic acid.
The solution was dissolved to give a concentration of μg / ml, 100 μl of this solution was added to each well, and the mixture was allowed to stand at room temperature for 2.5 hours.

Then, in order to suppress non-specific adsorption, bovine serum albumin (BSA) in phosphate buffered saline (P
Each well was blocked by adding 200 μl of (BS) solution (10 mg / ml) to each well and allowing it to stand at room temperature for 30 minutes. Furthermore, 100 μl of PBS solution (10 μg / ml) of human plasma-derived fibronectin (Chemicon International) was added to each well and left at room temperature for 1 hour to bind fibronectin to collagen coated on each well. As a model of extracellular matrix.

Next, a PBS solution of the partially purified protease derived from P. gingivalis which is an adhesion promoting factor (3.
7 μg / ml) 100 μl to each well and add 37 ° C.
After reacting for 30 minutes at 100 μl, 100 μl of PBS solution of biotinylated fimbriae (10 μg / ml) was added to each well and allowed to stand at room temperature for 30 minutes to cause an adhesion reaction.

The amount of finbrie adhered to each well is PBS.
After thorough washing with, the biotin was detected by streptavidin-conjugated alkaline phosphatase and quantified by measuring the absorbance at 405 nm. That is, the vector
100 μl of the streptavidin-conjugated alkaline phosphatase solution in the laboratory kit diluted 1000 times with PBS was added to each well and left for 30 minutes at room temperature, and then 100 μl of alkaline phosphatase substrate solution was added to each well and reacted for 30 minutes at room temperature. , 405 nm absorbance was measured. An appropriate amount of each polyphenol fraction was added when P. gingivalis-derived protease was added (control is PB
S) and IC ₅₀ were calculated by a conventional method.

Inhibitory activity against adherence of fimbriae derived from CP gingivalis to fibroblasts; normal human skin fibroblasts (NHDF, Kurashiki Spinning Co., Ltd.) were used in F-GM medium (Kurashiki Spinning Co., Ltd.). The cells were cultured in a 96-well multiplate (3 × 10 ⁵ cells / 96 wells). After washing the cultured cells with PBS and blocking each well with BSA as in the previous section, the procedure after the addition of the protease derived from P. gingivalis was performed in the same manner as in the previous section to quantify the amount of adhered fimbriae to determine each polyphenol fraction. The minute IC ₅₀ was calculated.

Inhibitory activity against P. gingivalis-producing protease of each polyphenol fraction measured in the above AC, and extracellular matrix (laminin, collagen, fibronectin, etc.) of fimbriae (pilus component protein) derived from the same and fibroblast. The inhibitory activity against cell adhesion is shown in Table 2.

[0053]

[Table 2]

Example 6 Toothpaste: A dentifrice having the following composition was prepared according to a conventional method. (Composition) Heavy part Dicalcium phosphate 42 Glycerin 18 Carrageenan 0.9 Sodium lauryl sulphate 1.2 Sodium saccharin 0.09 Butyl paraoxybenzoate 0.005 Perfume 1 High molecular weight polyphenol ^* 0.05 Water remaining total amount 100 * A-AE obtained in Example 1 (acetone elution fraction of acacia bark extract)

Example 7 Mouthwash: A mouthwash having the following composition was prepared by a conventional method. (Composition) Heavy parts Sodium lauryl sulfate 0.8 Glycerin 7 Sorbitol 5 Ethyl alcohol 15 High molecular weight polyphenols ^** 0.05 L-Menthol 0.05 Perfume 0.04 Saccharin sodium 0.1 Water residual amount 100 * * W-AE obtained in Example 1 (acetone elution fraction of wattle tannin)

Example 8 Chewing gum: A chewing gum having the following composition was prepared according to a conventional method. (Composition) Weight part Gum base 20 Calcium carbonate 2 Stevioside 0.1 High molecular weight polyphenol ^*** 0.01 0.01 Lactose 76.89 Flavor 1 Total 100 *** OTE-AE (oolong tea) obtained in Example 1 Acetone elution fraction of extract)

Example 9 Candy: A candy having the following composition was prepared according to a conventional method. (Composition) Weight part Granulated sugar 55 Hydroxy candy 43.5 Citric acid 1.0 Fragrance 0.2 Color element 0.2 High molecular weight polyphenol ⁺ 0.1 Total amount 100 + A-ME obtained in Example 1 (Methanol elution fraction of acacia bark extract)

Example 10 Fruit Juice Beverage: A fruit juice drink (juice) having the following composition was prepared according to a conventional method. (Composition) Weight part Frozen concentrated Unshu mandarin orange juice 5 Fructose glucose liquid sugar 11 Citric acid 0.2 L-ascorbic acid 0.02 Perfume 0.2 Chromium 0.1 High molecular weight polyphenol ⁺⁺ 0.2 Water residue Quantity Total quantity 100 ++ OTE-ME obtained in Example 1 (methanol elution fraction of oolong tea extract)

[0059]

The high-molecular-weight polyphenol, which is an active ingredient of the anti-periodontal disease drug of the present invention, inhibits the adhesion of P. gingivalis, which is a causative bacterium of periodontal disease, to periodontal tissues.
It prevents the development and progression of periodontal disease and has no unique taste or odor. Therefore, the anti-periodontal disease agent containing the high molecular weight polyphenol as an active ingredient can be widely used for preventing periodontal disease as an oral hygiene agent or a food additive. that's all

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Ryuji Tanaka 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka Suntory Biomedical Research Institute

Claims (10)

[Claims] 1. A weight average molecular weight of 800 to 10,000
An anti-periodontal disease agent containing 0 as a polyphenol having a degree of polymerization of 3 to 30 as an active ingredient. 2. The anti-periodontal disease treating agent according to claim 1, wherein the polyphenol is a polyphenol derived from the heartwood or bark of trees. 3. Polyphenol is a legume (Leguminosae)
The anti-periodontal disease agent according to claim 1 or 2, which is a polyphenol derived from the tree. 4. The anti-periodontal disease agent according to claim 1, wherein the polyphenol is derived from fermented tea leaves. 5. The anti-periodontal disease treating agent according to claim 1, wherein the polyphenol is derived from a plant of the genus Rosaceae Pyracantha. 6. The anti-periodontal disease medicine according to claim 1, which is an oral hygiene agent. 7. The anti-periodontal disease agent according to claim 1, which is a food additive. 8. A weight average molecular weight of 800 to 10,000
An anti-periodontal disease food containing 0 and a polyphenol having a degree of polymerization of 3 to 30. 9. A process for producing an anti-periodontal disease substance, which comprises subjecting a heartwood or bark of a tree, fermented tea leaves or a plant of the genus Pyracantha of the family Rosaceae to solvent extraction and subjecting the extract to adsorption color chromatography. 10. A weight average molecular weight of 800 to 10,000
The method for producing an anti-periodontal disease substance according to claim 9, which is a polyphenol having a degree of polymerization of 0 to 3 and a degree of polymerization of 3 to 30.