WO2006106994A1

WO2006106994A1 - Drug for periodontal disease comprising component extracted from aesculus hippocastanum l.

Info

Publication number: WO2006106994A1
Application number: PCT/JP2006/306978
Authority: WO
Inventors: Keisuke Kajita; Young-Soo Kim; Hideaki Kitagori
Original assignee: Kobayashi Pharmaceutical Co., Ltd.
Priority date: 2005-03-31
Filing date: 2006-03-31
Publication date: 2006-10-12
Also published as: WO2006106994A8; JP2006282562A

Abstract

[PROBLEMS] To provide a novel drug for periodontal disease which has an excellent effect of inhibiting abnormal extension of a gingival epithelial tissue. [MEANS FOR SOLVING PROBLEMS] A drug for periodontal disease containing a component which is obtained by extracting Aesculus hippocastanum L. with a solvent and isolating; and a composition to be used in the oral cavity for treating oral diseases such as gingivitis and periodontitis which contains the above drug.

Description

An agent for periodontal disease containing an extract of Amanita cinnamon

Technical field

TECHNICAL FIELD [0001] The present invention relates to a novel agent for periodontal disease that inhibits abnormal extension of gingival epithelial tissue involved in the cause of oral diseases such as gingivitis and periodontitis (periodontal disease).

Background art

Periodontal tissue that surrounds the tooth neck and root of a mammalian tooth is composed of gingiva (gum), periodontal ligament, cementum, and alveolar bone, and plays a role in supporting the tooth. Inflammatory symptoms appear in this periodontal tissue, and the inflamed area stops at the gingiva, which is called “gingivitis”, and the inflamed area extends beyond the gingiva to the periodontal ligament and alveolar bone. The state that has reached is distinguished from "periodontitis". In both gingivitis and periodontitis, inflammation in the periodontal tissue is affected by plaques formed by the growth of bacteria attached to food residues in the oral cavity and other environmental factors. Due to As for gingivitis, the site of inflammation is limited to the gingiva, and inflammation has not spread to the periodontal ligament or alveolar bone. Can be relieved or cured. On the other hand, if the symptom progresses to periodontitis, the connective tissue adhesion between the gingiva and the tooth is lost, so not only the tooth swings but also the periodontal ligament and alveolar bone. Injury's destruction and simply physically cleaning the oral cavity will make it difficult to expect periodontitis to recover. In addition, as the periodontal tissue is destroyed due to the development of periodontitis, the gingival epithelial cells expand toward the root of the tooth (down-gloss), resulting in a periodontitis that is characteristic between the gum and the tooth. Gingival sulcus, the so-called periodontal pocket, is formed.

[0003] As a method of chemically treating inflammation of periodontal tissue involved in the development of periodontitis using a pharmaceutical compound, using ε-aminocaproic acid having an excellent anti-inflammatory effect, Techniques that suppress the onset of gingivitis and periodontitis symptoms by antiplasmin action are used. Or a drug to remove Tetracycline-resistant Sraphylococci, the causative agent of periodontal and inflammatory inflammation, that is, tetracycline There is also a technique using minocycline hydrochloride.

[0004] In addition, as a drug for removing the causative bacteria that have settled in the periodontal pocket and the staying phase (biofilm), macrolide antibiotics, specifically, lactone ring is used. Depending on the number of atoms constituting, there are 14-membered to 16-membered substances such as erythromycins, 16-membered macrolide josamycins, clarithromycins and the like. Among these, 14-membered macrolide antibiotics are useful because they can effectively prevent and eliminate biofilm formation.

[0005] By the way, about 60% of the components of the periodontal knitting and weaving are collagen, and as the degradation of collagen proceeds, a phenomenon of shrinking or receding gingiva is induced. A group of metalloenzymes that act on the extracellular matrix such as collagen and promote its degradation is generally called matrix meta-oral protease (hereinafter simply referred to as “MMP”).

[0006] In addition to periodontitis and gingivitis, MMP plays a central role in the degradation of extracellular matrix in various pathologies such as cancer (cancer) disease, ulceration, rheumatoid arthritis, and osteoporosis. (See Non-Patent Document 1). MMP is produced by a wide variety of cells, including collagenase (MMP-1 and MMP-8), stromelysin (MMP-3), and gelatinase (MMP-2 and MMP-9). The above enzyme molecular species have been reported so far (see Non-Patent Document 2). Among these, collagenase is not normally produced from epithelial cells, but it has been reported that it is expressed around the adhering epithelium and periodontal pocket epithelium of periodontal tissue (see Non-Patent Document 3). In addition, gelatinase has been reported to be produced by epithelial cell force due to stimulation by lipopolysaccharide derived from periodontal disease-causing bacteria and to degrade type IV collagen, which is a component of the basement membrane. In other words, this suggests that the increase in MMP activity is closely correlated with the progression of periodontal disease. In fact, the amount of MMP contained in the mouth washes, gingival crevicular fluid and saliva of periodontal patients reflects the pathology of periodontal patients. A decrease in the amount of MMP has also been reported (see Non-Patent Document 4). In addition, when the amount of MMP and TIMP held by gingivitis patients and healthy subjects were measured, the amount of MMP in gingivitis patients was very high, and the amount of MMP in patients with periodontitis also increased. Was also reported to be significant (non-patented) (Ref. 5). Therefore, substances that inhibit MMP enzyme activity and MMP production are considered to be useful in promoting the suppression of the progression of periodontal diseases associated with local inflammation. Non-Patent Document 1: Nakata, Okada, "Respiration", 18, 4, pp.365-371 (1999)

Non-Patent Document 2: Yoshihara, Shinna, "Inflammation and Immunity", 2, pp.177-185 (1994)

Non-Patent Document 3: M. Kylmaniemi, et al: J. Dent Res., 75, pp. 919-926 (1996) Non-Patent Document 4: M. Makela, et al: J. Dent Res., 73, pp. 1397-1406 (1994)

Non-Patent Document 5: A. Haerian, et al: J. ClinPeriodontoL, 22, pp.505-509 (1995) Disclosure of the Invention

Problems to be solved by the invention

[0007] The present invention inhibits the abnormal extension of gingival epithelial tissue in mammals and prevents the formation of periodontal pockets, thereby effectively inhibiting the progression of oral diseases such as periodontitis. The purpose is to provide a new agent for periodontal disease that maintains healthy gingival tissue.

Means for solving the problem

[0008] That is, the gist of the present invention is that, in addition to being a well-known medicinal plant from ancient times, Aesculus hippocastanum, which has been confirmed to be safe for humans, is extracted with a solvent. It is an agent for periodontal disease which contains the obtained separated component and inhibits abnormal extension of gingival epithelial tissue in mammals. Moreover, according to the other aspect of this invention, the composition for oral cavity containing the periodontal disease agent of this invention is also provided.

[0009] As a result of intensive studies by the inventors of the present application, a separated component obtained by extracting cypress with a solvent exhibits abnormal extension of gingival epithelial tissue, particularly gingival epithelial tissue in mammals. As a result, it was found that it was significantly inhibited, and it was found to be applicable to uses such as prevention and treatment of oral diseases such as periodontitis.

The invention's effect

[0010] According to the present invention, a novel agent for periodontal disease that can inhibit the abnormal extension of the gingival epithelial thread and tissue and can effectively suppress the formation of periodontal pockets is realized.

BEST MODE FOR CARRYING OUT THE INVENTION

[0011] The constitution of the periodontal disease agent of the present invention will be described in detail below. [0012] According to one aspect of the present invention, a periodontal that contains an isolated component obtained by extracting Aesculus hippocastanum with a solvent and inhibits abnormal extension of gingival epithelial tissue in a mammal. A disease agent is provided.

As used herein, the term “gingival epithelial cells” refers to epithelial cells of the oral cavity mucosa (oral cavity) that surround the tooth neck and root and serve as a supporting structure for adjacent tissues. This epithelial cell adheres to the surface of the tooth enamel layer and forms a periodontal pocket as the periodontitis progresses. In addition, the oral mucosal epithelial cells are always placed in an environment that is exposed to the risk of infection by bacteria, and therefore, the oral mucosal epithelial cells in other parts of the oral cavity are excellent, such as cell division. It has a distinction from the nature it has.

[0014] The cypress (Aesculus hippoca stanum L.), which provides an active ingredient in the agent for periodontal disease of the present invention, is a deciduous tree that originates from the northern part of Greece and comes from the Turkish region. Contains ingredients that quickly relieve swelling caused by inflammation during trauma!

[0015] This cypress is applied to an extraction process using a solvent. The cypress or any of its parts (eg branches, leaves, stems, husks, fruits or roots) that are applied to the extraction process can be left intact, physically broken or otherwise Depending on the situation, the powder can be dried and pulverized and processed into powder, and the force can be applied to the extraction process.

[0016] As the solvent used in this extraction step, a solvent known in the art can be used, and for example, a lower alcohol, a polyhydric alcohol, a nonpolar solvent, a polar solvent, and the like can be used.

[0017] Examples of lower alcohols include alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropyl alcohol, and butanol; examples of polyhydric alcohols include glycerin and polyethylene glycol; examples of nonpolar solvents include pentane. Saturated hydrocarbons such as hexane, heptane, octane, nonane and decane; polar solvents include water, warm water (hot water), acetone, ethyl acetate, and methyl acetate. As the solvent, it is possible to select and use only one of the above-mentioned solvents, and it is also possible to use a combination of two or more kinds of solvents. For example, in the case of using a raw material with a large amount of fat, it may be degreased and extracted with a non-polar solvent and then extracted with an arbitrary solvent or with water The extraction treatment can also be performed using a solvent.

[0018] As a method for extracting Japanese cypress, methods well known in the art can be used. For example, Japanese cypress itself, its coarsely pulverized or cut product, or its dried crushed product (powder) is immersed in a solvent by cold immersion, digestion, etc., or while heated and stirred. A method of performing extraction and obtaining an extract containing a desired separation component through filtration, and a bar-collation method can also be used.

[0019] The extract obtained in this manner is used as it is, or the solvent is distilled off, depending on the mode of use, after removing unnecessary solid matter by filtration or centrifugation as necessary. And partially concentrated or dried. The isolated product obtained by concentration or drying may be used after being purified by washing with a non-soluble solvent, or may be used by further dissolving or suspending the product in an appropriate solvent. You can also.

[0020] Alternatively, a fraction having a desired inhibitory activity is obtained and purified by using a conventional purification method such as a countercurrent distribution method or liquid chromatography. It is also possible to use it.

[0021] Furthermore, the solvent extract obtained as described above can be processed into a dried concentrated extract form by ordinary drying means such as reduced pressure drying or freeze drying.

[0022] Further, according to a preferred embodiment of the present invention, there is also provided an oral composition comprising the periodontal disease agent of the present invention as an active ingredient. As long as it does not adversely affect the inhibitory effect of the agent for periodontal disease of the present invention, other components generally used in oral compositions, such as adhesives, cooling agents, Binders, sweeteners, flavorings, disintegrants, lubricants, colorants, sustained release regulators, surfactants, solubilizers, wetting agents, pH adjusters, etc. can be added optionally.

[0023] Examples of the pressure-sensitive adhesive include water-soluble polymer substances derived from polysaccharides, cellulose polymer substances, synthetic polymer substances, natural polymer substances, amino acid polymer substances, rubber polymer substances, and the like. Is available. For example, pullulan, pullulan derivatives, and polysaccharides such as starch; hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methenoresenorelose, hydroxyethino retino leneno relose, canoleboxy methino renolose Salts (such as carboxymethylcellulose, sodium carboxymethylcellulose and potassium carboxymethylcellulose), methinoresenolellose, ethylcellulose, polyacrylic acid, polyacrylate (sodium polyacrylate and acrylic acid / octyl acrylate co-polymer) ) And copolymers of methacrylic acid

cellulosic polymeric materials such as n-butyl polymer, methacrylic acid and methyl methacrylate polymer and methacrylic acid and ethyl acrylate polymer; carboxyvinyl polymer, polyethylene glycol, polyvinylpyrrolidone, Synthetic polymer materials such as polyvinyl alcohol; lectin, alginic acid, alginate (sodium alginate, potassium alginate, magnesium alginate, propylene glycol alginate ester, triethanolamine alginate, triisopropanolamine alginate, ammonium alginate Natural polymer substances such as sodium chondroitin sulfate, agar, chitosan and carrageenan; collagen and gelatin, etc. Amino acid based polymeric material; and can arabic gum, Karaya gum, tragacanth gum, xanthan gum, locust bean gum, Guagamu, that our rubber-based polymer material such as the force present invention, such as tamarind gum and Jierangamu, Te suitably used.

[0024] Examples of the refreshing agent include 1-menthol, cQ-menthol, heart force oil, camphor, heart force water, borneol, peppermint essential oil, spearmint essential oil, and the like that can be used in the present invention. Any one of these can be used alone, or two or more can be used in combination.

[0025] Examples of binders include sugars (such as glucose), sugar alcohols (such as sorbitol, xylitol, erythritol, mannitol), polybulurpyrrolidone, starches, macrogol, dextrin, tragacanth, gelatin, polybulul alcohol, Shellac, gum arabic, sodium alginate, hydroxypropylcellulose, and the like are available in the present invention, but are not limited to these. The above can also be used together.

[0026] Examples of sweeteners include saccharin sodium, stepioside, stevia extract, and Asvalte. , Xylitol, syrup, honey, sorbitol, maltitol, mannitol, saccharides (lactose, sucrose, fructose, glucose, etc.) can be used in the present invention, but are not limited thereto. Either one of these can be used, or two or more can be used in combination.

[0027] Natural flavors (spearmint oil, varnish oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, heart power oil, power rudamon oil, Coriander oil, mandarin oil, lime oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, orina gum oil, pine-dollar oil, etc.), synthetic Fragrance (Carbon, Anethole, Cineol, Methyl salicylate, Cynamic aldehyde, Eugenol, Thymol, Linalol, Linalyl acetate, Limonene, Menthon, Menthyl acetate, Pinene, Octylaldehyde, Citral, Pregon, Calbele acetate, Anisaldehyde Natural fragrances listed above and , Or a blended fragrance obtained by mixing a fragrance arbitrarily selected from synthetic fragrances, etc., which can be used in the invention of the present application. Two or more types can be used in combination.

[0028] Examples of the disintegrant used in the present invention include starches, methylcellulose, crystalline cellulose, cellulose derivatives (such as sodium carboxymethylcellulose), alginic acid, alginates, carbonates, organic acids, polyvinyl pyrrolidone, and cross-linked polybutylpyrrolidone. It can be used, but not limited to these, only one of these can be used, or two or more can be used in combination.

[0029] Lubricants include talc, metal stalagmites, fatty acids (such as stearic acid), stearates (such as magnesium stearate), talc, sucrose fatty acid esters, hydrous silicon dioxide, light anhydrous key acid, dried Hydroxy-aluminum gel, macrogol, etc. can be used in the present invention, but are not limited to these, use only one of these V, or use two or more together You can also

[0030] As the coloring agent, blue 1, No. 4, titanium dioxide, copper chlorophyllin sodium and the like can be used in the invention of the present application. Can be used, or two or more types can be used in combination. [0031] Preservatives include benzoic acids, salicylic acids, sorbic acids, norabens, cetylpyridinium chloride, decalinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine chloride, chlorhexidine dalconate, isopropylmethylphenol, Forces that can be used in the present invention, such as trickle san, hinokitiol, phenol, etc., are not limited to these. Any one of these forces can be used, or two or more can be used in combination.

[0032] As the sustained release modifier, polyvinyl acetate, ethyl cellulose, aminoalkyl metaacrylate copolymer and the like that can be used in the present invention S, and any one of these not limited to these 1 It is possible to use only one type or use both.

[0033] As the surfactant, sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil, sorbitan monostearate, polysorbate, glyceryl monostearate, sodium lauryl sulfate, lauromacrogol and the like can be used in the present invention. A certain force is not limited to these. Any one of these may be used, or two or more may be used in combination.

[0034] As the solubilizer, glycerin, concentrated glycerin, propylene glycol, ethanol, fluidized << Raffin, purified water, macrogol, polysorbate, and the like can be used in the present invention, but are not limited thereto. Either one of these forces can be used, or two or more can be used in combination.

[0035] As the wetting agent, glycerin, propylene glycol, sorbitol solution, water, ethanol, dilute ethanol and the like are not limited to these, and only one of these is used. Or, use two or more types together.

[0036] As the pH adjuster, lactic acid, pantothenic acid, phosphate, malic acid, citrate, and the like can be used in the present invention. Can be used, or two or more types can be used in combination.

[0037] As the dosage form of the oral composition of the present invention, any of tablets, pills, granules, solutions, sheets, gels, pastes and the like can be used. In particular, the oral cavity of the present invention When the composition for dental use is a dental preparation, it should be in the form of toothpaste, mouthwash, oral pasta, troche, etc. It can effectively cope with the prevention and treatment of oral diseases caused by destruction of periodontal tissues such as

[0038] The present invention will be described below with reference to examples thereof, but it is needless to say that the present invention should not be interpreted in a limited manner based on the disclosure of the examples.

Example

[0039] A: Gingival ten.

Gingival epithelial tissue (about 5.0 mm × about 5.0 mm slice) was collected from the oral cavity of a healthy human gingival tissue. Collected tissue pieces are washed with phosphate buffer (1 X 10 ⁵ U / ml).

It was immersed in penicillin, 100 μg / ml streptomycin, and 80 μg / ml kanamycin), and was cut into small sections of about 0.5 mm × about 0.5 mm with a scalpel within 24 hours. The small section was placed on a well of a type I collagen-coated 6-well plate. After confirming adhesion between the small section and collagen, the primary culture medium (L-glutamine, 10%

DMEM / Ham's F12 medium (Dainippon Pharmaceutical Co., Ltd.) containing FBS, 10 pg / ml EGF, and 80 μg / ml kanamycin was gently poured into the well. The culture system thus prepared was cultured under conditions of 37 ° C. and 5% carbon dioxide, and the primary culture medium was replaced with fresh one once every two days.

[0040] Small section force After confirming that epithelial cells proliferate, that is, epithelial cells proliferate to an extent that covers approximately 30% of the wells, the medium is subcultured ( EDGS and EpiLife medium (casdade) containing 80 μg / ml kanamycin) were exchanged. The culture solution was transferred to a type I collagen-coated T75 flask and subculture was performed at a cell density of 2500 cells / cm ² according to the cell growth rate. The gingival epithelial cells used in the following examples were obtained. Obtained

[0041] B: ^ l G .; ^

First, an inflammation induction medium for artificially inducing periodontitis was prepared. Recombinant human TNF-α, an inflammation-inducing substance, was purchased from PEPROTECH (Size B

vial: 50 μg, 300-01A; Lot No. 121CY25). 50 μg of recombinant human TNF-a at room temperature Then, after standing for 1 hour, it was applied to a desktop centrifuge. Dissolve the precipitate obtained by centrifugation in 500 μl of distilled water and add 0.1 mg / ml.

After adding Tris buffer, 361 of the obtained aqueous solution was further dissolved in 3.564 ml of physiological saline (PBS (−)). The PBS solution thus obtained was dispensed in 1.2 ml portions into a serum tube and stored at a temperature of 120 ° C. The remaining aqueous solution was dispensed 100 μl into a serum tube and stored at a temperature of 20 ° C. Dissolve 1.2 ml of PBS solution (containing 1 μg / ml TNF-a) in 10.8 ml of EpiLife medium (without serum and antibiotics) and filter and filter with a 0.2 m pore size filter. After sterilization, a medium for inducing inflammation was obtained.

[0042] Next, cinnamon cinnamon extract powder was added to 0.02 g / ml (75% ethanol).

A solution in which the component concentration of 2% w / v) was dissolved was obtained.

[0043] The solution containing the component extracted from Cypress japonica was filtered and sterilized using a 0.2 µm pore size filter, and the component concentration was adjusted using an inflammation-inducing medium.

[0044] Inhibition of gingival epithelial cell extension according to the present invention with respect to a solution containing an extract component derived from Japanese cypress is Masami Yoshioka, et al, 'Effect

of Hydroxamic Acid Based Matrix Metalloproteinase

The assay was performed according to the procedure reported in the literature of Inhibitors on Human ingival Cells and Porphyromonas gingivalis, .1. Periodontol. Vol.74, pp.1219-1224 (2003).

[0045] First, gingival epithelial cells are placed on a 24 well plate (1.8 cm ² Zwell) at a ratio of 2 X 10 ⁴ Zwell. Once every two days, the subculture medium was replaced with fresh one and the culture was continued until the cells covered the entire well. After confirming that the cells covered the entire well, half the cells of the well were scraped with the tip of the pipette tip. After washing the well with PBS, pour the inflammation-inducing medium and a solution containing extract components (1.0% or 0.1% concentration) from Cypress and cultivate under conditions of 37 ° C and 5% carbon dioxide. At the time of 0, 24, and 48 hours after the start of culturing, the photographs of the wells were taken to verify the degree of cell spreading (FIG. 1 (b)). In addition, a test group following the same procedure was used as a control except that the well was washed with PBS and then only the medium for inflammation induction was poured (Fig. L (a)). [0046] The moving distance of the cells was visually determined based on a photograph of the cells that appeared on the well.

[0047] Based on the comparison with the distance traveled in the control, the gingival epithelial cell growth-inhibiting effect by the extract derived from Japanese cypress is a remarkable inhibitory effect (+++), an inhibitory effect on strength (++) The grading was performed according to a four-step evaluation of normal inhibitory effect (+) and no inhibitory effect (one). The evaluation results are summarized in Table 1 below.

[0048] [Table 1]

As is clear from the results shown in Table 1, it was confirmed that the separated component obtained by extracting cypress with a solvent significantly inhibited the growth of gingival epithelial cells, and that this inhibitory effect was concentration-dependent. It was. The test result is in

This is the first stage of the in vivo test, and it can be expected to have a sufficient inhibitory effect on the growth of gingival epithelial cells in vivo.

[0049] C: Cattle. Gingival warts in the body. Extension of skin cells. Determination of harmful effects

In this example, 12-week-old wistar male rats were used, and D. Ekuni,

et al "Protease augment the effects of lipopolysacchande

in rat gingiva, .1. Periodont

According to the procedure reported in the literature of Res, vol.38, pp.591-596 (2003), the gingival epithelial cell spreading inhibitory effect was assayed. That is, as the periodontal tissue destruction due to the development of periodontitis progresses, healthy gingival epithelial cells (Fig. 2 (a)) downgrow toward the root (Fig. 2 (b)), As a result, a gingival crevice (periodontal pocket) peculiar to periodontitis is formed between the gingiva and the tooth. By paying attention to the phenomenon peculiar to this symptom, we examined the effect of inhibiting the growth of gingival epithelial cells in vivo.

[0050] First, Escheric hia in the bilateral maxillary first molar palatal gingival sulcus of a 12-week-old male wistar rat Endotoxin derived from Escherichia coli (LPS, 25 μg / 1; SIGMA) and protease from Streptomyces griseus (TYPE XIV 4 units / mg ゝ 2.25 units / μl [0.56mg dissolved in 1 μ1]; SIG MA) 1.5 1 was administered once a day for 4 consecutive weeks to induce periodontitis.

[0051] Then, the rats were divided into a group of administration of cypress extract and a control group. In other words, in the group of administration of cinnamon extract, two weeks after the start of LPS and protease treatment, O.lg of cereal extract extract (Western genus extract (75% ethanol extract: Omni force Co., Ltd.)) was added. 1.5 1 of a 1% aqueous solution (0.2 mg / ml) of a solution obtained by dissolving in 75% ethanol with an aqueous solution obtained by diluting 5 times with distilled water was treated once a day for 2 weeks. . In the control group, LPS and protease treatment was started and after 2 weeks, no treatment was performed.

[0052] After the experiment, the test control tissue site was fixed (reflux + soaked), and after decalcification, it was embedded in paraffin to prepare a 4 m thick tongue-like section. Next, hematoxylin 'eosin staining was performed and microscopically observed to confirm the presence and extent of downgrowth of the gingival epithelial tissue.

As a result, in the control group, gingival downgloss was confirmed 4 weeks after the start of the test (FIG. 3 (a)). On the other hand, in the cypress extract group, gingival downgrowth was not observed 4 weeks after the start of the test (Fig. 3 (b)), and healthy tissue was maintained.

[0054] From this result, it was confirmed that the separated component obtained by extracting cypress with a solvent significantly inhibits the growth of gingival epithelial cells in vivo.

[0055] D: Preparation of oral composition

A composition for oral cavity for various uses was prepared, which was prepared by blending an extract of Japanese cypress (1.0%), which demonstrated the effect of inhibiting the growth of gingival epithelial cells in Example B and Example C. In addition, the unit of the component compounding amount in the present Example is indicated by weight% unless otherwise specified.

[0056] D— 1: Toothpaste

The materials listed in Table 2 below were mixed and kneaded at room temperature to prepare a toothpaste.

[0057] [Table 2] Dibasic calcium phosphate 30.00

Glycerin 10.00

Sorbitol 20.00

Carpoxymethylcellulose sodium 1.00

Sodium lauryl sulfate 1.50

Carrageenan 0.50

Saccharin sodium 0.10

Perfume 1.00

Sodium benzoate 0.30

Japanese horse chestnut extract 0.50

Purified water balance

100.00

D— 2: Toothpaste

Toothpastes were prepared by mixing and kneading the materials shown in Table 3 below at room temperature.

[Table 3]

D—3: Mouthwash

A mouthwash was prepared by mixing the materials shown in Table 4 below at room temperature.

[Table 4]

D-4: oral cavity The materials listed in Table 5 below were mixed at room temperature to prepare an oral pasta.

[0060] [Table 5]

D-5: Troche To the granules obtained by mixing maltitol, gum arabic, citrate, amla extract and xylitol listed in Table 6 below at room temperature, add sucrose fatty acid ester and powder flavor. And troche was prepared.

[Table 6]

Industrial applicability

The agent for periodontal disease of the present invention is useful as a means for preventing and treating oral diseases such as gingivitis and periodontitis.

Brief Description of Drawings

FIG. 1 is a schematic diagram for explaining the principle of a gingival epithelial cell extension inhibition test.

FIG. 2 is a schematic diagram illustrating the principle of extension of gingival epithelial tissue.

FIG. 3 is a photograph showing the extension state of gingival epithelial thread and tissue in (a) a control group and (b) a group of components extracted with Japanese horse chestnut extract.

Claims

The scope of the claims

[1] Se = 1 Utochino (Aes cuius hippocastanum

And an agent for periodontal disease, which comprises a separated component obtained by extraction with a solvent and inhibits abnormal extension of gingival epithelial tissue in mammals.

[2] The agent for periodontal disease according to claim 1, which is in the form of a dry extract.

[3] The agent for periodontal disease according to claim 1 or 2, wherein the mammal is a rat.

[4] An oral composition comprising the periodontal disease agent according to any one of claims 1 to 3.