JP2000256154A - Pharmaceutical composition, oral composition, and food and drink composition, for treating or prophylactic disease accompanying degeneracy of gingival connective tissue or decrease of alveolar bone - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject composition capable of manifesting excellent effect on the therapy or prophylaxis of a disease accompanying degeneracy of gingival connective tissue or decrease of alveolar bone by including a specific stilbene-based compound or the like as an active ingredient. SOLUTION: This composition contains at least one kind selected from a stilbene compound of the formula (A and B are each a halogen, an amino, an amidino or the like; n and m are each 0-5) and a polymer thereof, (e.g. resveratrol), preferably in the proportion of 0.005-1 wt.% as an active ingredient. The compound of the formula is preferably derived from one or more kinds of plants selected from a plant of Polygonaceae, a plant of Vitaceae, Veratrum album and Morus alba. The daily dose of the compound of the formula is, for example, about 10-100 mg per adult in the case of aggressive oral administration of the compound, aiming at the reduction or treatment of the symptom.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a pharmaceutical composition, an oral composition, and a food or drink containing a specific stilbene compound useful for treating or preventing a disease associated with degeneration of gingival connective tissue or a decrease in alveolar bone. Composition.

[0002]

2. Description of the Related Art A portion having a function of supporting a tooth and absorbing an external force applied to the tooth is called a periodontal tissue and is composed of gingiva, periodontal ligament, alveolar bone, and cementum. Diseases that involve the degeneration of gingival connective tissue and the resorption of alveolar bone ultimately result in permanent loss of teeth, which not only has a major impact on daily life, but also impairs nutrition, such as malnutrition caused by indigestion. It has been known to have serious effects on health.
Many diseases related to these are known, and among them, periodontal disease is regarded as a representative causal disease. Plaque and tartar are initial factors as the causes of periodontal disease, and in addition to local factors such as dietary content, oral cleaning status, formation of periodontal pockets, oral environment, etc.
Systemic factors such as systemic disease, aging, stress, endocrine system factors, and genetic diseases are also known. Various treatments have been applied to these, but further prevention or improvement of the regression of gingival connective tissue and the resorption of alveolar bone are desired.

[0003]

DISCLOSURE OF THE INVENTION The present invention provides a pharmaceutical composition, an oral composition, and a food and drink composition having an excellent effect in treating or preventing a disease accompanied by degeneration of gingival connective tissue or alveolar bone loss. To provide.

[0004]

Means for Solving the Problems As a result of intensive studies on physiologically active substances contained in plant components, the present inventors have found that stilbene compounds prevent gingival connective tissue degeneration and prevent and improve the resorption of alveolar bone. It has been found that the present invention has an effect, and the present invention has been completed. That is, the present invention provides the inventions described in the following items. Item 1 General formula (1)

[0005]

Embedded image

Wherein A and B are the same or different and are each a halogen atom, an amino group, an amidino group, an anilinoamide group,
Mercapto group, sulfonic acid group, phosphoric acid group, hydroxy C
₁ -C ₅ alkyl group, a sugar residue or -OR ₁ (R ₁ is a hydrogen atom, C ₁ -C ₅ alkyl group, a hydroxy C ₁ -C ₅ alkyl or C ₂ -C ₅ alkenyl group.) Or -O
COR ₂ (R ₂ represents a hydrogen atom, a C ₁ -C ₅ alkyl group, a hydroxy C ₁ -C ₅ alkyl group or a C ₂ -C ₅ alkenyl group). n and m are the same or different and are 0
Represents an integer of from 5 to 5. A pharmaceutical composition for treating or preventing a disease associated with degeneration of a gingival connective tissue or a decrease in alveolar bone, comprising as an active ingredient at least one selected from a stilbene compound represented by the formula object. Item 2 Treatment of a disease associated with degeneration of gingival connective tissue or reduction of alveolar bone, characterized by containing at least one selected from a stilbene compound represented by the general formula (1) and a multimer thereof as an active ingredient. Or a prophylactic oral composition. Item 3 Treatment of a disease associated with degeneration of gingival connective tissue or reduction of alveolar bone, characterized by containing at least one selected from a stilbene compound represented by the general formula (1) and a multimer thereof as an active ingredient. Or a food or drink composition for prevention. Item 4 The compound represented by the general formula (1) is
At least 3, 5, and 4 'position are the same or different and a hydroxyl group, a sugar residue or -OCOR ₂ [R ₂ are as defined above. The compound according to any one of claims 1 to 3, which is a compound substituted with a compound represented by the formula: Item 5: The compound represented by the general formula (1) is derived from one or more plants selected from the group consisting of Polygonaceae or grape, diatomaceous, and mulberry. 5. The composition according to any one of the above items 4.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Stilbene used in the present invention (stilbene)
The bene) -based compound has the general formula (1):

[0008]

Embedded image

Wherein A and B are the same or different and are each a halogen atom, an amino group, an amidino group, an anilinoamide group,
Mercapto group, sulfonic acid group, phosphoric acid group, hydroxy C
₁ -C ₅ alkyl group, a sugar residue or -OR ₁ (R ₁ is a hydrogen atom, C ₁ -C ₅ alkyl group, a hydroxy C ₁ -C ₅ alkyl or C ₂ -C ₅ alkenyl group.) Or -O
COR ₂ (R ₂ represents a hydrogen atom, a C ₁ -C ₅ alkyl group, a hydroxy C ₁ -C ₅ alkyl group or a C ₂ -C ₅ alkenyl group). n and m are the same or different and are 0
Represents an integer of up to 5. ].

A halogen atom is a fluorine atom, a chlorine atom,
Examples thereof include a bromine atom and an iodine atom. 1-5 carbon atoms
Examples of the alkyl group include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, t
Examples thereof include a linear or branched alkyl group such as an ert-butyl group and an n-pentyl group. Examples of the hydroxyalkyl group having 1 to 5 carbon atoms include linear or branched such as hydroxymethyl group, hydroxyethyl group, hydroxy n-propyl group, hydroxyisopropyl group, hydroxy n-butyl group, and hydroxy n-pentyl group. And hydroxyalkyl groups. Examples of the alkenyl group having 2 to 5 carbon atoms include linear groups such as vinyl group, isopropenyl group, allyl group, 2-butenyl group, 3-butenyl group, 1-methylallyl group, 2-pentenyl group, and 3-pentenyl group. Or a branched alkenyl group. Examples of the sugar residue include monosaccharides such as pentose and hexose and derivatives thereof (eg, deoxy sugar, amino sugar, uronic acid, sugar alcohol, etc.), disaccharides, trisaccharides and the like.

The sugar residue referred to in the present invention is a group in which the hydrogen atom of the hydroxyl group bonded to the glycoside carbon atom at the reducing end of the sugar is removed. Examples of pentose include D-arabinose, L-arabinose, and D-arabinose. Xylose, L-xylose, D-ribose, D-ribulose and the like. Examples of hexose include D-galactose, L-galactose, D-glucose, D-fructose, D-mannose, D-talose, L-sorbose, D-tagalose and the like.

Examples of the deoxy sugar include the above-mentioned monosaccharide deoxy sugars, for example, D-2-deoxyribose, L-rhamnose, L-fucose and the like.
Examples of amino sugars include the amino sugars of the monosaccharides described above, for example, N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid, and the like. Examples of uronic acids include glucuronic acid, mannuronic acid, galacturonic acid, iduronic acid and the like. Examples of sugar alcohols include D-glucitol, D-glucitol
-Mannitol, ribitol, galactitol and the like.

Examples of disaccharides include disaccharides obtained by appropriately combining the monosaccharides described above.
For example, it is represented by sucrose, lactose, trehalose, maltose, soloobiose, xylobiose, melibiose, rutinose, vicianose, trehalosamine, chondrosin and the like. Examples of trisaccharides include trisaccharides obtained by appropriately combining the monosaccharides described above. For example, it is represented by raffinose, maltotriose, cellotriose, manninotriose and the like.

In the general formula (1), n and m each represent an integer of 0 to 5, but may be the same or different.
The composition of the present invention may contain a multimer such as a dimer or trimer of the compound represented by the general formula (1). As the dimer, α-viniferin (α-Viniferin; a dimer of resveratrol); as the trimer, ε-viniferin (ε-Viniferin; resveratrol) ); Tetramers include Hopephenol (Hopeaphenol; Resveratrol)
ratrol) tetramer) and the like.

Preferred compounds among the stilbene compounds represented by the general formula (1) and their multimers are shown below. (1) a compound in which both n and m are 0 [that is, stilbene] (2) a stilbene-based compound in which n and m are the same or different and are integers of 0 to 5, and all the substituents are hydroxyl groups ( However, n and m are not simultaneously 0). As a specific example, 4,4′-stilbenediol (4,4-stilbenedio
l), 3,5-stilbenediol,
Resveratrol [that is, 3,5,4'-stilbenetriol (3,5,4'-stilbenetriol)] and the like. (3) A stilbene compound in which n and m are the same or different and are each an integer of 0 to 5, and one of the substituents is a sugar residue (however, n and m are not simultaneously 0).
As a specific example, Rhaponticin (ie,
4'-methoxy-3,3 ', 5-stilbenetriol-3-glucoside)], polydatin (ie, pie seed
d) or 3,5,4'-stilbenetriol-5-glucoside (3,5,4'-stilbenetriol-5-glucoside)], 3,4'5-stilbenetriol-4'-glucoside (3,4 '5-stilbenetr
iol-4'-glucoside), 2,3,5,4'-stilbenetetraol-2-glucoside (2,3,5,4'-stilbenetetraol-2-gluco)
side). (4) stilbene compounds wherein n and m are the same or different and are each an integer of 0 to 5, and a substituent is present at least at the 3-, 5-, and 4'-positions (provided that the sum of n and m is 3 or more; is there.). Specific examples include resveratrol, rapontisine, polydatin, 3,4'5-stilbenetriol-4'-glucoside, 2,3,5,4'-stilbenetetraol-
2-glucoside and the like. (5) A stilbene compound in which n and m are the same or different and are each an integer of 1 to 5, and a substituent is present at least at the 4- and 4-positions. As a specific example, stilbamidine (St
ilbamidine) [ie, 4,4'-diamidinostilbene (4,4 '
-diamidinostilbene)], 4,4'-diaminostilbene and 4,4'-stilbenediol. (6) A stilbene compound in which n and m are the same or different and are each an integer of 0 to 5, and one of the substituents is a sulfonic acid group or a carboxy group (n and m are not simultaneously 0). Specific examples include 4,4′-diamino-2,2′-stilbene disulfonic acid (4,4′-diamino-2,
2'-stilbenedisulfonic acid), 2-carboxy-3, 4'-stilbenediol (2-carboxy-3, 4'-stilbenediol) and the like. (7) A stilbene compound in which n and m are the same or different and each is an integer of 0 to 5, and one of the substituents is an alkoxy group (however, n and m are not simultaneously 0). As a specific example, 4-methoxystilbene (4-meth
oxystilbene), 2,5′-dimethoxy-4,4′-stilbenediol (2,5′-methoxy-4, 4′-stilbenediol) and the like. (8) stilbene compound substituent is -OR _1. (9) Dimers of the compounds of (1) to (8). A specific example is α-viniferin which is a dimer of resveratrol. Among the compounds shown above,
The stilbene compounds of (2), (3) and (4) are preferred.
A 5- or 4′-substituent having the same or different hydroxyl group,
-OSOR preferably stilbene compound is ₂ or sugar residues, in particular resveratrol, Poridatin are preferred. Further, as the multimer, α-viniferin and ε
-Viniferin is preferred.

When the composition of the present invention is a food or drink composition, the stilbene compound (8) is preferred. The stilbene compound represented by the general formula (1) can be synthesized by a known method, for example, by a Wittig reaction of a corresponding phosphonium salt and a corresponding aldehyde. (E. Reim
ann "Tetrahedron Letters" 47, 4051 (1970)).

The compound represented by the general formula (1) includes
A dried product, an extract, or the like obtained by subjecting a plant containing the compound to a treatment such as drying, extraction, and purification may be used. In the present invention, the case where such a dried product, extract or the like also passes is referred to as “plant-derived”. As such a plant, for example, a plant that contains about 0.0001% by weight or more of the compound of the general formula (1) in a dried product can be used. Examples of such a plant include a Polygonaceae plant, a grape plant, Diatoms, mulberry and the like.

The Polygonaceae plant used in the present invention is not particularly limited as long as it contains the stilbene compound represented by the general formula (1). Polygonum tinctorium ) Ibukinotorano ( Polygonum bistorta ), buckwheat ( Fagopyrum esculent )
um ), rhubarb ( Rheum spp. ), tsuldokudami ( Polygo )
num multiflorum ), knotweed ( Polygonum cuspidatu )
m ) and the like. Among them, especially rhubarb ( Rhe
um spp. ), Tsurukudami ( Polygonum multiflo rum ),
Itadori ( Polygonum cuspidatum ) is preferred because of its high content of stilbene compounds, more preferably
Polygonum multiflorum containing a large amount of resveratrol compound (Poly
gonum multiflorum ) and knotweed ( Polygonum cuspidatu )
m ) is preferred. The site to be used is not particularly limited, but a rhizome or a root is preferable.

Vitace (Vitace) used in the present invention
ae) is not particularly limited as long as it contains the stilbene compound represented by the general formula (1),
Representative plant varieties include Vitis sp.
p.). Specifically, European and Middle Eastern varieties of Vistis vinifera ( V.vinifra ) and North American varieties of Vistis labrusca ( V.labrusca ). 15 varieties represented by V. California. North American mucadin species Bistis musognana (V. Munso
niana). Asian varieties bistis
Three varieties represented by V. Amurensis are listed. This Some even Bisutisu Binifera species (V.vinifra), Bisutisu Vitis labrusca (V.labrusc
a ) and varieties developed in Japan are preferred. Specifically, Airen, Aligote, Riesling, Sauvignon Blanc
blanc, Trebbiano, Chardonnay, Chenin blanc, Semillon, Muscat, Cabernet Sauvignon, Calignan
rignan), Cinsaut, Grenache Noir, Merlot, Mataro
aro), Pinot Noir, Sangiovese, Syrah, Gama
y), Tempranillo, Trebbiano, Gewurtrami
ner), Zweigltrebe, Muller-Thurgau, Grollea
u), Cabernet Franc, Petit Verdot, Koshu, Muscat Berry A, and Gluck Queen. Among them, in particular, Cabernet Sauvignon (Ca) of Vistis Vinifera species ( V.vinifra )
bernet Sauvignon), Pinot Noir, Syrah, Merlot, Grenache
nache), Carignan, Nebbiolo (Neb)
biolo), Sangiovese (Sangiovese), Gamay (G
amay), Bistis labrusca species (V.labrusca), Muscat berry A, and Gluck queen are preferable because they contain a large amount of stilbene compounds. The site to be used is not particularly limited, either, but leaves or fruits (including pericarp and seeds) are preferred. In the case of fruits, immature ones are preferable because they contain more stilbene compounds.

The diatoms used in the present invention ( Veratr)
um album ) It is a plant of the lily family, and the site to be used is not particularly limited, but a rhizome is preferable. The site of mulberry used in the present invention is not particularly limited, but "mulberry nut" is preferable.

Plants containing the above-mentioned stilbene compounds may be used as they are after natural drying, hot-air drying, freeze-drying or fermentation, or may be concentrated, extracted, powdered, etc. according to a conventional method. The product obtained by performing the above process is used. Examples of such a method include a method described in JP-A-61-171427.

The amount of the stilbene compound represented by the general formula (1) in the composition of the present invention is not particularly limited as long as the desired effect of the present invention can be obtained. It can be set appropriately according to the requirements.
0001-5% by weight, further 0.001-1% by weight,
Particularly, 0.005 to 1% by weight is preferable. These ranges are preferable from the viewpoint of solubility, palatability and the like.

When the composition of the present invention is used as a pharmaceutical product, it can be prepared into various preparations such as powders, granules, tablets, capsules, solutions, ointments, creams, gels, patches, etc. Can be used for injections, percutaneous absorptions, oral preparations, oral patches, injection preparations in periodontal pockets, and the like. The preferable compounding amount of the compound of the general formula (1) in the present invention is as described above.
02% by weight or more, 0.005 for oral mucosa absorbent
% Weight or more is more preferable.

The administration method is not particularly limited and can be carried out according to various forms. For example, powders, granules, tablets, capsules, solutions and the like can be administered orally, and injections can be administered intravenously or intravenously. It can be administered intramuscularly, sarcastically, subcutaneously or intraperitoneally. Among these administration methods, the method of administering the composition of the present invention is preferably a method of absorption through oral mucosa or a method of injection into periodontal tissue.

The effect of the composition of the present invention can be further enhanced by combining one or more selected from therapeutic agents for bone metabolism, if necessary, in combination. Examples of therapeutic agents for bone metabolism include retinol, vitamin A compounds such as retinoic acid, cholecalciferol, ergosterol, 7-dehydrocholesterol, 22-dihydroergosterol, 7-dehydrositosterol, 7-dehydrostigmasterol, 7 -Dehydrocampesterol,
Ergocalciferol, Cholecalciferol, Vitamin D4, Vitamin D5, Vitamin D6, Vitamin D7
Vitamin D compounds such as phylloquinone, menaquinone,
Vitamin K compounds such as menadione, pulstaglandin compounds such as prostaglandin E1 and prostaglandin E2, calcitonin, parathyroid hormone, adrenocortical hormone and hormone compounds having hormone-like action, somatomedin, epidermal growth factor , Nerve growth factor, cartilage-derived factor, growth factors such as osteonectin, osteocalcin, cytokines, lymphokines, diphosphonates and the like.

When the composition of the present invention is used for the oral cavity, it can be blended with liquid, paste, ointment, powder and other preparations, and can be coated or blended with a fiber carrier such as floss. It can be used in the form of toothpaste, liquid toothpaste, mouthwash, mouth spray, toothbrush, dental floss, interdental cleaning tool and the like. The preferable compounding amount of the compound of the general formula (1) in the present invention is as described above, but is more preferably 0.005% by weight or more.

When the composition of the present invention is ingested as food or drink, it can be prepared in various forms such as, for example, lumps, liquids, syrups, powders, and jellies according to a conventional method. Examples include soft drinks, juices,
Beverages (drinks) such as tea; powdered drinks such as powdered juices and soups; confectionery such as cookies, biscuits, cereals, chewable tablets, chewing gum, candy, gummy, wafers, and crackers; dressings, sauces, and powder seasonings Seasonings such as ingredients; staple food products such as bread, noodles, rice cakes; food for the sick, foods for specified health use,
It can be used as a functional food such as a dietary supplement, and candies, chewing gum, gummy, and chewable are preferred because they can be retained in the oral cavity for a long time and taken. In the present invention, as long as the effects of the present invention are not impaired, components usually used for pharmaceuticals, foods, and oral preparations, for example, other medicinal components, nutrients, animal and plant components, excipients, bulking agents, sweeteners, flavors Agents, coloring agents, preservatives, emulsifiers, solubilizers, hydrotropes and the like can be appropriately compounded.

The dose or intake of the composition of the present invention is appropriately determined depending on the form, age and sex of the patient or the recipient, other conditions, the degree of the disease, and the like. Specifically, when the stilbene compound of the general formula (1) is taken for a long period of time in a daily diet for prevention, the amount of the stilbene compound of the general formula (1) per day is about 0.1 to 500 mg, preferably 0 to 500 mg per adult. The amount is preferably about 0.5 to 100 mg, more preferably about 1 to 50 mg.

In the case of active administration or ingestion for the purpose of alleviation or treatment of symptoms, and oral administration or ingestion, it is usually 1 to 500 m / adult per day.
g, preferably about 10 to 500 mg, and more preferably about 10 to 100 mg. When administered directly into the body such as by intravenous injection, the dose is preferably about 0.01 to 50 mg per adult per day. The composition of the present invention can be administered or ingested once or several times a day.

[0030]

EXAMPLES Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples. In addition, the numerical value of the compounding amount means "% by weight" unless otherwise specified. Example 1 Patch for Improving Oral Bone Metabolism A patch for improving oral bone metabolism was prepared according to a conventional method by mixing the components according to the following formulation. Ingredients Amount (%) Glycerin 76.9 Triacetin 17.0 Hydroxyethylcellulose 4.0 Copolymer of ethyl acrylate and methyl methacrylate and 2.0 trimethylammonium ethyl methacrylate Resveratrol 0.1 Total 100.0

Example 2 Preventive Food for Diseases Associated with Degeneration of Gingival Connective Tissue or Decrease in Alveolar Bone Diseases Associated with Degeneration of Gingival Connective Tissue or Decrease in Alveolar Bone According to the Conventional Method Tablets were prepared. Ingredients Blended amount (%) Collagen protein hydrolyzate 30.0 Calcium carbonate 10.0 Magnesium carbonate 5.0 Sucrose fatty acid ester 2.0 Flavor 0.5 Crystalline cholecalciferol 0.3 Aspartame 0.05 Resveratrol 0. 001 Palatinose Remainder Total 100.0

Example 3 Beverage for Prevention of Disease Associated with Degeneration of Gingival Connective Tissue or Reduction of Alveolar Bone Each component is mixed according to the following production method, and degeneration of gingival connective tissue or alveolar bone for the elderly according to a conventional method. A beverage for preventing a disease accompanied by a decrease in the amount was prepared. A 25% skim milk solution is inoculated with lactic acid bacteria, cultured until the pH is about 4, and homogenized. Then, 6.5 parts of sugar, 10 parts of orange juice, pectin 3
The sweetener prepared by dissolving 0 parts in water is added to the homogenized yogurt at a weight ratio of 4: 5 and mixed. Furthermore,
A mixture of calcium gluconate and magnesium gluconate at a weight ratio of 2: 1 and 10 parts dissolved in water was added at a ratio of 20% by weight, followed by mixing. Finally, a grape leaf extract (resveratrol content) (0.05%).

Example 4: Dentifrice A dentifrice was prepared according to a conventional method by mixing the components by the following production method. Ingredients Amount (%) Calcium pyrophosphate 42.0 Glycerin 20.0 Grape skin extract 10.0 (Resveratrol content 0.005%) Sucrose fatty acid ester 2.0 Sodium lauryl sulfate 1.5 Carrageenan 1.0 Flavor 1 0.0 Sodium lauroyl sarcosinate 0.5 Stevia extract 0.1 Purified water Remainder Total 100.0

Example 5: Mouthwash Mouthwash was prepared according to a conventional method by mixing the components according to the following production method. Ingredients Amount (%) Ethyl alcohol 40.0 Glycerin 15.0 Grape juice juice cake extract 10.0 (Resveratrol content 0.001%) Sucrose fatty acid ester 2.0 Polyoxyethylene (60) hydrogenated castor oil 1.0 Fragrance 0.5 Stevia extract 0.01 Chlorhexidine 0.005 Purified water Remainder Total 100.0

[0035]

EFFECTS OF THE INVENTION The administration, ingestion and use of the pharmaceuticals, foods and drinks, and oral preparations of the present invention can treat or prevent diseases associated with degeneration of gingival connective tissue or reduction of alveolar bone.

Continued on the front page (51) Int.Cl. ⁷ Identification code FI Theme coat II (reference) A61K 35/78 A61K 35/78 CE V F term (reference) 4C083 AA072 AA112 AB292 AB322 AC061 AC102 AC122 AC171 AC331 AC351 AC422 AC432 AC471 AC551 AC662 AC742 AC771 AC782 AC791 AC811 AC901 AD132 AD202 AD222 AD282 AD352 AD391 AD392 AD412 AD432 AD472 AD652 CC41 DD15 EE31 EE32 EE33 EE34 4C088 AB12 AB34 AB43 AB56 AC04 AC05 AC13 BA07 BA08 CA03 CA25 MA05 MA06 MA07 MA37 MA32 MA67 MA32 MA32 MA32 MA35 MA32 MA35 MA67 MA32 MA32 MA32 MA32 MA32 MA32 MA35 MA32 MA32 MA35 MA32 MA32 MA67 ZA96 ZB22 4C206 AA01 CA17 FA31 JA32 MA01 MA04 MA37 MA48 MA52 MA55 MA57 MA61 MA72 MA77 NA14 ZA67 ZA96 ZB22

Claims (5)

[Claims] 1. A compound of the general formula (1) Wherein A and B are the same or different and are each a halogen atom, an amino group, an amidino group, an anilinoamide group, a mercapto group, a sulfonic acid group, a phosphoric acid group, a hydroxy C ₁ -C ₅ alkyl group, a sugar residue or —OR. ₁ (R ₁ is a hydrogen atom, C _1-
C ₅ alkyl group, a hydroxy C ₁ -C ₅ alkyl or C ₂ -C ₅ alkenyl group. ) Or -OCOR
₂ (R ₂ is a hydrogen atom, a C ₁ -C ₅ alkyl group, a hydroxy C
Shows the ₁ -C ₅ alkyl or C ₂ -C ₅ alkenyl group. ). n and m are the same or different, and
Indicates an integer of 5. A pharmaceutical composition for treating or preventing a disease associated with degeneration of gingival connective tissue or alveolar bone, comprising as an active ingredient at least one selected from stilbene compounds represented by the formula object. 2. A compound of the general formula (1) Wherein A and B are the same or different and are each a halogen atom, an amino group, an amidino group, an anilinoamide group, a mercapto group, a sulfonic acid group, a phosphoric acid group, a hydroxy C ₁ -C ₅ alkyl group, a sugar residue or —OR. ₁ (R ₁ is a hydrogen atom, C _1-
C ₅ alkyl group, a hydroxy C ₁ -C ₅ alkyl or C ₂ -C ₅ alkenyl group. ) Or -OCOR
₂ (R ₂ is a hydrogen atom, a C ₁ -C ₅ alkyl group, a hydroxy C
Shows the ₁ -C ₅ alkyl or C ₂ -C ₅ alkenyl group. ). n and m are the same or different, and
Indicates an integer of 5. Or a stilbene compound represented by the formula [I] or a multimer thereof, for the treatment or prevention of diseases associated with degeneration of gingival connective tissue or reduction of alveolar bone. Composition. 3. General formula (1) Wherein A and B are the same or different and are each a halogen atom, an amino group, an amidino group, an anilinoamide group, a mercapto group, a sulfonic acid group, a phosphoric acid group, a hydroxy C ₁ -C ₅ alkyl group, a sugar residue or —OR. ₁ (R ₁ is a hydrogen atom, C _1-
C ₅ alkyl group, a hydroxy C ₁ -C ₅ alkyl or C ₂ -C ₅ alkenyl group. ) Or -OCOR
₂ (R ₂ is a hydrogen atom, a C ₁ -C ₅ alkyl group, a hydroxy C
Shows the ₁ -C ₅ alkyl or C ₂ -C ₅ alkenyl group. ). n and m are the same or different, and
Indicates an integer of 5. ] A food or drink for the treatment or prevention of a disease associated with degeneration of gingival connective tissue or reduction of alveolar bone, characterized in that at least one selected from stilbene compounds represented by the formula [1] and multimers thereof is used as an active ingredient. Product composition. 4. The compound represented by the general formula (1) is the same or different at least at the 3-, 5- and 4'-positions, and a hydroxyl group, a sugar residue or —OCOR ₂ [R ₂ is the same as described above. The composition according to any one of claims 1, 2 and 3, wherein the composition is a compound substituted by the formula: 5. The compound represented by the general formula (1) is derived from one or two or more plants selected from the group consisting of Polygonaceae or grape, diatomaceous, and mulberry. Item 5. The composition according to any one of Items 1 to 4.