JP2003081800A - Anti-periodontitis agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an anti-periodontitis agent containing extracts of herbal medicines safe for human body and effective for preventing and treating periodontitis. SOLUTION: This anti-periodontitis agent is characterized by containing extracts of at least one herbal medicine selected from pine needle, clove, rosemary, linderae radix, cherry tree bark, Magnolia hypoleuca, Magnolia Kobus and polygoni radix as the active component and having growth inhibitory action for periodontitis protist microbe Porphyromonas gingivalis and inhibitory action for Porphyromonas gingivalis producing collagenase.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an anti-periodontal disease drug effective for the prevention and treatment of periodontal disease. More specifically, the present invention is derived from a natural plant that inhibits the growth of Porphyromonas gingivalis known as a periodontopathic bacterium and further has an action of inhibiting collagenase produced by this bacterium. It relates to an anti-periodontal disease drug.

[0002]

BACKGROUND OF THE INVENTION Periodontal disease is an inflammatory disease of bacterial origin, and its factors are increased periodontopathic bacteria, invasion of bacteria into tissues, and host response to infection. Porphyromonas gingivalis
Is a bacteria that is considered to be the most likely pathogen of adult periodontitis, which is said to be the most common periodontal disease, and is frequently isolated from the deep periodontal pocket of patients with periodontal disease. Further, this bacterium is a non-motile Gram-negative bacillus that forms black colonies on a blood plate medium, and is known to produce enzymes such as collagenase, phospholipase A, alkaline phosphatase, and acid phosphatase. There is. Among them, collagenase is said to be a direct factor leading to gingival tissue destruction because it has a function of degrading collagen in periodontal tissue. Therefore, in order to effectively prevent and treat periodontal disease, it is important to suppress the growth of Porphyromonas gingivalis in the periodontal pocket and inhibit the action of the enzyme produced by the bacterium. .

Conventionally, antibiotics such as tetracycline and minocycline have been used as agents for improving the symptoms of periodontitis by inhibiting the growth of periodontopathic bacteria. However, while such antibiotics have a strong action and excellent effects, there are problems such as the emergence of drug-resistant bacteria and side effects, and their use is limited.

Therefore, there is an urgent need for the development of a drug which has no side effects and is highly safe to the human body, and which is comparable to or more effective than the above antibiotics.

[0005]

SUMMARY OF THE INVENTION The present invention is intended to solve the above-mentioned conventional problems. That is, an object of the present invention is to provide an anti-periodontal disease drug which has a growth inhibitory action against Porphyromonas gingivalis, which is known as a pathogen of periodontal disease, but is safe for the human body. In particular, the present invention is an anti-periodontal disease agent effective for the prevention and treatment of periodontal disease by having both the growth inhibitory action against the periodontopathic bacteria and the action inhibiting collagenase produced by the bacteria. The purpose of the present invention is to provide an anti-periodontal disease drug that is free from side effects.

[0006]

In view of the above problems, the inventors of the present invention have inhibited growth of Porphyromonas gingivalis, which is safe for the human body and is considered as a causative bacterium of periodontal disease. After researching day and night for substances that show action, the above-mentioned growth on various plants such as pine needles, cloves, rosemary, mulberry, cherry bark, magnolia, Chinese herbs, and hempen that have been widely used as crude drugs. It was found to have an inhibitory effect. After further studies based on such findings, it was found that this crude drug also has an action of inhibiting collagenase produced by Porphyromonas gingivalis, which is extremely useful for treatment and prevention of periodontal disease. It was confirmed that it can be prepared as an effective anti-periodontal disease drug. The present invention has been completed based on such findings. That is, the present invention is the following anti-periodontal disease drugs: Item 1. A periodontopathic bacterium Porphyromonas containing an active ingredient of an extract of at least one crude drug selected from the group consisting of pine needles, cloves, rosemary, mulberry powder, cherry bark, koboku, kansai Gingivalis ( Porphyromonas
gingivalis ) and an inhibitory action on the Porphyromonas gingivalis-produced collagenase. Item 2. The crude drug extract is used as a flow extract in the case of mulberry, scallop, bark or Chinese cabbage, and as a tincture in the case of mulberry,
Item 1. The anti-periodontal disease drug according to item 1. Item 3. A composition for oral cavity containing the anti-periodontal disease drug according to Item 1 or 2.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION As the active ingredient of the anti-periodontal disease agent of the present invention, at least one selected from the group consisting of pine needles, cloves, rosemary, mulberry powder, cherry bark, pomegranate, Chinese cabbage, and radish
Mention may be made of extracts of herbal medicines. These crude drugs are plant-based crude drugs that have been used since ancient times and their safety has been confirmed.

The pine needles are Pinus densiflora Sieb.
et Zuee. [Japanese red pine]), which has been used as a crude drug not listed in the Japanese Pharmacopoeia for the prevention and treatment of rheumatism, beriberi, and frostbite; cloves are Syzygium aromaticum Merrill et Perry ( Eugenia
Caryophyllata Thunberg) ( Myrtaceae ) is a bud or leaf, and is conventionally used as a crude drug listed in the Japanese Pharmacopoeia for Kampo prescription medicines of various prescriptions such as stomachic medicine; Rosemary ( Rosemarinus officinalis L.) is It is a crude drug not listed in the Japanese Pharmacopoeia and is conventionally used as an anti-inflammatory, analgesic, digestive function improving drug; the crow drug is Lindera strychnifolia F. Villars ( Laura
ceae)) is the root of, are those conventionally used in Chinese medicine prescription drugs for a variety of prescription, such as gastrointestinal drugs from as herbal medicines listed in the Japanese Pharmacopoeia outside the herbal medicine standard; Sakurakawa is, Yamazakura (Prun
us jamasakura Siebold) or other closely related plants ( Rosac
eae ) (for example, Yoshino cherry tree) is a bark without pericardium, and is conventionally used as a herbal medicine not listed in the Japanese Pharmacopoeia for various prescriptions such as cold remedies and antitussives and expectorants. It is a thing; Koboku is a honoki Magnolia ob
ovata Thunberg, Magnolia officinalis Rehder et Wil
son or Magnolia officinalis Rehder et Wilson va
It is the bark of r. biloba Rehder et Wilson ( Magnoliaceae ), and is used as a crude drug listed in the Japanese Pharmacopoeia for various kinds of prescription Kampo medicines such as stomachic and analgesic and antispasmodic drugs; Magnolia salicifolia
Maximowicz), Magnolia kobus De Candoll
e), a bud of Magnolia biondii Pampanini or other closely related plants ( Magnoliaceae ), which has been used as a crude drug listed in the Japanese Pharmacopoeia standard for traditional Chinese medicines such as Kakkonto Kagawa / Saiyoku and Saiyokuseikanto. Is present;
What is the dragon, Polygonum multiforum Thunb
erg ( Polygonaceae )), which has been used for traditional Chinese medicine such as Toki-inko as a crude drug listed in the Japanese Pharmacopoeia standard for foreign drugs.

These herbal medicines may be subjected to extraction operation as they are (raw) or as crushed parts of each plant, or may be dried and, if necessary, subjected to extraction operation in the form of pulverized powder. Good.

As the extraction solvent, for example, water, an organic solvent or a mixture thereof can be mentioned. The organic solvent is not particularly limited, but methanol,
1 carbon atom such as ethanol, propanol and butanol
4 lower alcohols; lower alkyl esters such as ethyl acetate; glycols such as ethylene glycol, butylene glycol, propylene glycol and glycerin; other polar solvents such as ethyl ether, acetone, acetic acid; hydrocarbons such as benzene and hexane; Known organic solvents such as nonpolar solvents such as ethers and petroleum ethers can be mentioned. Water and alcohol are preferable. These solvents may be used alone,
It is also possible to use two or more kinds in combination. For example, if necessary, an appropriate amount of water may be added to the above organic solvent to be used as a water-containing organic solvent, and as such, a mixed solvent of water and alcohol can be preferably mentioned. In the present invention, water, alcohol (for example, ethanol, etc.) or a mixed liquid of water and alcohol is more preferable, and in the case of the mixed liquid, an aqueous solution containing 20 to 40% by weight of ethanol can be exemplified.

As the extraction method, a commonly used method can be adopted. For example, a wide range of extraction methods used for the preparation of various galenical preparations such as extract, elixir, dip / decoction, flow extract and tincture can be mentioned. it can. Although not limited, for example, the above crude drug (as is (raw)
Or coarse powder, finely chopped products), or dried crushed products (powder, etc.) of cold (usually ~ 25 ° C) or warm soaking (usually 35 ~ 45 ° C)
And the like, a method of performing extraction while heating and stirring, and obtaining an extract by filtration, a percolation method (usually 1 to 30 ° C.), and the like.

The obtained extract may be used as it is, after removing solid matter by filtration or centrifugation if necessary, or may be used as it is, or after distilling off the solvent and partially concentrating or drying it. May be. After concentration or drying, the obtained concentrate or dried product may be washed with a non-soluble solvent for purification and used, or may be further dissolved or suspended in an appropriate solvent for use. In addition, the extract is subjected to a conventional purification method, for example, countercurrent partitioning method or liquid chromatography to determine the growth inhibitory activity against Porphyromonas gingivalis and / or the activity to inhibit the collagenase produced by the bacterium. Get the fractions that have,
It is also possible to purify and use. Furthermore, in the present invention, for example, the solvent extract obtained as described above can be used as a soft extract by concentration under reduced pressure, or as an extract dried product by a usual means such as reduced pressure drying or freeze drying.

When the crude drug used as a raw material of the present invention has a strong aroma due to, for example, the essential oil contained in the crude drug, and when the aroma impairs its application to foods and the like, the crude drug is beforehand extracted from the essential oil. It is preferable to perform the above extraction treatment after removing the components. The removal of the essential oil component is not particularly limited, but the crude drug of interest is subjected to steam distillation as it is or after being dried and pulverized, or to a hexane-free solution.
It can be carried out by extraction treatment with a low polar solvent.

Among the various herbal medicines used in the present invention, pine needles, cloves and rosemary can be used as an extract. These extracts may be prepared according to the above method, or conveniently, commercially available pine needle extracts,
What is marketed as a clove extract and a rosemary extract can also be used.

[0015] Among the above herbal medicines, it is preferable to prepare and use mulberry powder, scaly skin, green bark and radish as an extract or flow extract. These extract or flow extract may be prepared according to the conventional method prescribed in the Japanese Pharmacopoeia, but conveniently, the extract or flow extract (Kuraku flow extract, Sakura skin flow extract, Koboku flow extract) is used. It is also possible to use a commercially available product as "and syrup extract". Furthermore, it is preferable to prepare and use Beingou as a tincture. These tinctures may be prepared according to the conventional method defined by the Japanese Pharmacopoeia, but conveniently any commercially available tincture of tincture may be used.

When preparing the extract, the concentration of the crude drug can be adjusted by using an excipient. Examples of such excipients include liquid glucose, malt extract, and glycerin in the case of soft extracts; starch, sucrose, lactose, licorice powder, magnesium carbonate, magnesium oxide, calcium phosphate, and the like in the case of dry extracts.

The anti-periodontal disease drug of the present invention may consist of an extract of the above crude drug or may contain it as an active ingredient. When contained as an active ingredient, the compounding ratio of each herbal medicine extract for exhibiting anti-periodontal disease activity can be appropriately selected from the range of 0.001 to 25%.

Further, the anti-periodontal disease agent of the present invention is incorporated as a component of various oral compositions such as foods, quasi-drugs or pharmaceuticals to prevent and treat periodontal disease in the oral cavity. It can be used effectively.

Therefore, the present invention provides an oral composition containing the above-mentioned crude drug extract as an anti-periodontal disease agent.

Here, the oral composition includes both those which are orally ingested such as food and drink and those which are used in the oral cavity such as toothpaste and mouthwash.

Specific examples of the oral composition include various foods such as troche, chewing gum, candy, gummy candy, chocolate and juice; dentifrice (paste, liquid, solid powder), mouth spray, etc. Drugs or quasi drugs such as refreshing agents, chewing agents, troches, oral pasta agents, mouthwashes, syrups; dentifrices,
Oral cosmetics such as mouthwash and mouth rinse can be mentioned. Preferable examples include foods such as troches, chewing gum and candy, and mouthwashes such as dentifrice, mouthwash and mouthrinse.

These forms and dosage forms are not particularly limited and can be arbitrarily determined according to the type.

The mixing ratio of the anti-periodontal disease agent in the oral composition is such as the type of crude drug contained in the anti-periodontal agent, the effective concentration of the crude drug extract, the type of oral composition, the dilution in the mouth, etc. It can be appropriately selected and determined in consideration of the above factors. The compounding ratio of the anti-periodontal disease agent per 100% by weight of the oral composition is usually 0.001 in terms of the concentration of each herbal medicine extract.
-25 wt%, preferably 0.01-10 wt% can be appropriately selected and adjusted.

The anti-periodontal disease drug of the present invention is an antibacterial agent (growth inhibitor) against periodontopathic bacteria, which may become publicly known or may become publicly known in the future, as other components unless it impairs the effects of the present invention. It can also be blended in combination with a component such as an inhibitor of collagenase produced by pathogenic bacteria or an anti-inflammatory agent.

Further, the anti-periodontal disease agent of the present invention can be used in combination with the components usually added to the oral cavity composition depending on the type of the oral cavity composition to be applied.

For example, in the case of toothpaste, an abrasive such as dicalcium phosphate, calcium carbonate, insoluble sodium metaphosphate, amorphous silica, aluminum oxide; carboxymethyl cellulose, hydroxyethyl cellulose, alginate, carrageenan, gum arabic, polyvinyl alcohol, etc. Binders of polyethylene glycol, sorbitol, glycerin, propylene glycol and other thickeners;
Sodium lauryl sulfate, sodium dodecylbenzene sulfonate, hydrogenated coconut fatty acid monoguiceride sodium monosulfate, sodium lauryl sulfoacetate,
Examples thereof include foaming agents such as sodium N-lauroyl sarcosinate, N-acyl glutamate, sucrose fatty acid ester, and the like. Further, flavoring agents such as menthol and flavoring agents or sweeteners, preservatives and the like which are usually used for this can be mentioned. It can be blended. Also in the case of mouthwashes such as mouthwash and foods such as chewing gum, the components in the usual manner can be used together. The sweetener to be used in combination is preferably one having low caries or no caries, and preferred examples thereof include D-xylose, xylitol, sodium saccharin, aspartame and trehalose.

Furthermore, the anti-periodontal disease agent of the present invention is lysozyme chloride, lytic enzyme, dextranase, mutanase, chlorhexidine, sorbic acid, alexidine, hinokitiol, cetylpyridinium, alkylglycine, alkyldiaminoethylglycine salt, monofluoro. It can also be used in combination with components such as sodium phosphate, sodium fluoride, stannous fluoride, water-soluble primary or secondary phosphates, quaternary ammonium compounds, and sodium chloride.

[0028]

The present invention will be described in more detail with reference to test examples and examples, but the present invention is not limited to these examples. Reference Example 1 Pinus densiflora Sieb. Et Zuee.
After putting rough cuts of leaves, and adding water to 3 volumes of ethanol and adjusting the volume to 10 volumes of hydrous ethanol (hereinafter referred to as "30% ethanol"), thoroughly mix and moisten the leaves. The mixture is sealed, left at room temperature for 2 days, and then naturally filtered to obtain the first leachate. Also 30% again on the residue
Ethanol is added, and the mixture is allowed to stand for 2 days in the same manner and then naturally filtered to obtain the second leachate. Second leachate is 60
Concentrate under reduced pressure below ℃, combine with the first leachate,
30% ethanol is added, and the amount of liquid is 1 ml.
It was adjusted so as to contain, and after standing for 2 days, it was filtered using diatomaceous earth. The obtained filtrate was used as a pine needle extract.

Reference Example 2 Preparation of clove extract A clove ( Syzygium aromaticum Merrill et Perry was added to a container.
[ Eugenia caryophyllata Thunber]) (Myrtaceae) is taken, and 30% ethanol is added in an amount of 2 times, mixed well and moistened, then sealed and left to stand at room temperature for 2 days, and then naturally filtered. Use 1 exudate. Also the residue again 30
% Ethanol is added in an amount of 2 times, and the mixture is allowed to stand for 2 days in the same manner and then naturally filtered to obtain a second leachate. The second leachate was concentrated under reduced pressure at 60 ° C or lower, combined with the first leachate, and 30% ethanol was added again to adjust the liquid volume so that 1 ml of the drug substance was contained in 1 ml. ,
Filtered with diatomaceous earth. The obtained filtrate was used as a clove extract.

Reference Example 3 Preparation of rosemary extract 10 kg of dried rosemary ( Rosmarinus officinalis L.) was weighed in a container, and 40 L of 30% ethanol was added thereto, mixed well, and sealed at room temperature. After leaving it for 3 days, it is naturally filtered to obtain the first leachate. Further, 30 L of 30% ethanol was added to the residue again, and the mixture was allowed to stand for 2 days in the same manner and then naturally filtered to obtain the second leachate. The first leachate and the second leachate were combined and concentrated under reduced pressure at 60 ° C. or lower, then ethanol was added to make the total volume 10 L, and the mixture was left for 2 days and then filtered using diatomaceous earth. The obtained filtrate was used as a rosemary extract.

Reference Example 4 Preparation of Karakuryu Extract Tendaiyaku ( Lindera strychnifolia F. Villars ( L
auraceae )) 10 kg of dried crushed roots as raw material, 30% ethanol as the first and second leaching agents, according to the manufacturing method described in the Japanese Pharmacopoeia General Regulations "Flow Extract" Then, about 10 kg of leachate was obtained. The obtained leachate was used as an oolong extract.

Reference Example 5 Preparation of Sakura-rinshi Extract Using 10 kg of dried crushed bark excluding the pericarp of Yoshino cherry tree ( Prunus yedonsis Matsum.) As a raw material, an aqueous 30% ethanol solution was used as the first and second leaching agents. make use of,
Leaching treatment was performed according to the production method described in the Japanese Pharmacopoeia General Rules “Ryu Extract” to obtain about 10 kg of leachate. The resulting leachate was used as a scalp skin extract.

Reference Example 6 Preparation of Koboku-ryo Extract Using 10 kg of dried crushed product of Japanese Pharmacopoeia Koboku as a raw material,
Using 30% ethanol as the leaching agent and the second leaching agent, the leaching treatment was performed according to the production method described in the Japanese Pharmacopoeia General Rules “Flow Extract” to obtain about 10 kg of a leaching solution. The obtained leachate was used as a magnolia bark extract.

Reference Example 7 Preparation of Chinese herb extract Extract 10 kg of dried shredded buds of Tamshiba ( Magnolia salicifolia Maximowicz) was used as a raw material, and a 30% ethanol aqueous solution was used as the first and second leaching agents. According to the manufacturing method described in the general rule "flow extract," leaching treatment was performed to obtain about 10 kg of leachate. The resulting leachate was used as a spicy sauce extract.

Reference Example 8 Preparation of Hemp Tingle Tincture Polygonum multiforum Thunberg ( Polyg
onaceae )) 10kg of dried crushed tuberous roots
Using 0% ethanol as a leaching solution, 30 L according to the manufacturing method described in the Japanese Pharmacopoeia General Regulations "Tincture agent" cold leaching method
The immersion liquid of was obtained. The resulting leachate was used as a spicy sauce extract.

Test Example 1 Growth Inhibitory Action A growth inhibitory action against periodontopathic Porphyromonas gingivalis was measured using the various herbal extracts prepared in Reference Examples 1 to 8.

Specifically, first, GAM broth medium (G
An equal amount of the crude drug extract was added to AM broth (59 g, purified water 1000 ml) (2-fold dilution: 50% solution), and this was used as a test sample solution. Similarly, the test sample solution was diluted with GAM broth medium to a 24-well microplate to obtain 2, 4, 8, 16, 32, and 64-fold dilution series (crude drug concentration:
50%, 25%, 12.5%, 6.25%, 3.125% and 1.56%). Porphyromonas gingivalis strain ATCC33277 strain is added to each of these.
The mixture was added at a rate of 10% and statically cultured at 37 ° C. for 3 days under anaerobic conditions to examine the presence or absence of growth of the bacteria. Table 1 shows the results of the determination of the minimum inhibitory concentration of each herbal medicine extract from the presence or absence of growth of the bacteria on the third day after the culture. In the table, − means no growth of the bacterium, and + means growth of the bacterium.

[0038]

[Table 1]

From these results, it is found that all of pine needles, cloves, rosemary, mulberry, eucalypt, safflower, Chinese cabbage, and Heisei crow have a significant growth inhibitory effect on periodontopathic Porphyromonas gingivalis. There was found. In particular, a strong antibacterial action was recognized against cloves, rosemary, hempen, pine needles, magnolia, Chinese cabbage, mulberry, and cherry bark.

Test Example 2 Collagenase Inhibitory Action Using various crude drug extracts prepared in Reference Examples 1 to 8 as test subjects, the inhibitory action against periodontopathic Porphyromonas gingivalis produced collagenase was determined.

Collagenase inhibitory activity
It evaluated using CLN-100 (collagen technology workshop).
Specifically, the degradation product generated by reacting with collagenase in the presence of the subject using fluorescently labeled collagen as a substrate is selectively denatured at 35 ° C and then extracted with ethanol, and the fluorescence intensity of the extracted degradation product is measured. The collagenase inhibitory activity of the subject was calculated by measuring That is, the inhibition rate of collagenase activity was determined by using the reduction rate of collagenase activity when the test substance was decomposed as the inhibition rate.

(1) Preparation of Collagenase Solution A Porphyromonas gingivalis producing collagenase solution was prepared by the following method.

Blood plate medium (Tripticase soy Agar 40 g, hemin 5 m)
g, menadione 0.5mg, horse defibrinated blood 50m
l, Purified water 950ml) Porphyromonas gingivalis ATCC 33277 strain anaerobically cultivated for 4 days 1000ml of liquid medium for enzyme extraction (GAM broth 59g, purified water 1000ml)
And anaerobically cultured at 37 ° C. for 3 days. The culture solution was centrifuged (12000 × g, 20 minutes), the supernatant was saturated with 80% ammonium sulfate, and centrifuged again (12000 × g, 20 minutes). The obtained precipitate is 0.05M containing 5 mM calcium chloride.
It was dissolved in 250 ml of Tris-hydrochloric acid buffer (pH 7.5) and dialyzed sufficiently using the same buffer. The dialysis solution is filtered (0.22
μm, MILLIPORE) was used as a Porphyromonas gingivalis producing collagenase solution.

(2) Measurement of Collagenase Inhibitory Action The collagenase inhibitory action was measured for each of the crude drug extracts prepared in Reference Examples 1-8. Specifically, first, a collagenase solution (3.684 U / m) produced by Porphyromonas gingivalis
l) 100 μl, fluorescence-labeled collagen solution 200 μl, and diluted solution of each crude drug extract (dilution ratio: 10 times diluted solution (10%), 100
Double dilution liquid (1%), 1000 times dilution liquid (0.1%), 10,000 times dilution liquid
(0.01%)) Mix 100 μl to make a total of 400 μl.
The reaction was carried out at 0 ° C for 2 hours, and after the reaction, the fluorescence intensity of the decomposed product was measured to calculate the collagenase activity. The collagenase activity inhibition rate of the crude drug extract was calculated from the following formula (1U =
1 μg collagen degradation / min).

[0045]

[Equation 1]

The test results are shown in Table 2. The control collagenase activity was 3.684 U / ml.

[0047]

[Table 2]

From these results, the extracts of pine needles, cloves, rosemary, mulberry, eucalypt, cherry bark, Chinese cabbage, Chinese cabbage, and Chinese radish have an inhibitory effect on collagenase produced by Porphyromonas gingivalis. I understand.

<Examples> Examples of application of the anti-periodontal disease drug of the present invention will be described below as Examples. In each example, the pine needle extract (pine needle dry matter conversion: 8.8 g / 100 ml), clove extract (clove dried matter conversion: 6.6 g / 100 ml) prepared in the above Reference Examples 1 to 8 as crude drug extracts, Rosemary extract (Rosemary dry matter conversion: 7.4g / 100ml), Oyaku-ryu extract (Erythroid dry matter conversion: 1.89g / 100ml), Sakura peel flow extract (Sakura-kin dry matter conversion: 1.7g / 100ml) , Koboku-ryu extract (converted to dried green bean paste: 5.0 g / 100 ml), Ginseng-ryu extract (converted to dried bean paste: 6.0 g / 100 ml), or Heishankara tincture (equivalent to 4.6 g / 100 ml of Heisei-karasu dried product). The unit of each formulation means part by weight unless otherwise specified.

Example 1 Chewing gum Calcium carbonate 5.0 Crude extract 1.0 Gum base 30.0 Erythritol 10.0 Xylitol 40.0 Maltitol 12.0 Fragrance 1.0 Total 100.00.

Example 2 Tablet crude drug extract 1.0 Polydextrose 7.0 Sugar ester 2.0 Fragrance 1.0 Xylitol 15.0 Palatinose balance 100.0.

Example 3 Sugar-coated tablet 200 parts by weight of the tablet portion were sugar-coated with 130 parts by weight of the sugar-coated portion to prepare a mouth-cooling agent. Tablet portion crude drug extract 1.00 sugar ester 1.00 guar gum 0.20 aspartame 0.01 fragrance 1.00 palatinose balance 100.00 total sugar-coated portion Tricalcium phosphate 1.00 Aspartame 0.01 Gum arabic 0.50 Perfume 0.40 Carnauba wax 0.10 Shellac 0.20 Maltitol Balance 100.00 in total.

Example 4 Candy crude drug extract 2.0 xylitol 8.0 maltitol 10.0 aspartame 0.1 fragrance 0.2 palatinit balance 100.0 in total.

Example 5 Toothpaste Dicalcium Phosphate 30.0 Glycerin 10.0 Sorbitol 20.0 Sodium Carboxymethyl Cellulose 1.0 Sodium Lauryl Sulfate 1.5 Carrageenan 0.5 Sodium Saccharin 0.1 Perfume 1.0 Sodium Benzoate 0.3 Crude Extract 2.0 Water Residue Total 100.0.

Example 6 Toothpaste Sodium lauryl sulfate 0.80 Ethanolamido laurate 1.00 Propylene glycol 3.00 60% sorbit solution 35.00 Methylparaben 0.20 Butylparaben 0.01 Sodium saccharin 0.15 Gelatin 0.30 Fragrance 0.60 Sodium alginate 0.90 Sodium benzoate 0.10 Aluminum hydroxide 45.00 Monofluorinate Na 0.76 Crude drug extract 2.00 Water balance 100.00.

Example 7 Mouthwash Ethanol 10.00 Glycerin 5.00 Citric acid 0.01 Sodium citrate 0.10 Polyoxyethylene hydrogenated castor oil 0.50 Methyl paraoxybenzoate 0.10 Perfume 0.20 Herbal extract 3.00 Water balance 100.00 in total.

Example 8 Mouthwash Sodium lauryl sulfate 0.80 Ethanolamido 0.80 glycerin 12.00 Glycerin 12.00 Sodium saccharin 0.20 Mint oil 0.80 Arginine 0.10 Disodium hydrogen phosphate 0.50 Dipotassium hydrogen phosphate 0.08 Crude drug extract 3.00 Water balance 100.00 in total.

Example 9 troche maltitol 21.0 gum arabic 1.5 sucrose fatty acid ester 2.5 powdered flavor 1.0 citric acid 4.0 crude drug extract 1.0 xylitol balance 100.0.

Example 10 Pasta for oral cavity Liquid paraffin 13.00 Cetanol 10.00 Glycerin 25.00 Sorbitan monopalmitate 0.60 Polyoxyethylene sorbitan monostearate 5.00 Sodium lauryl sulphate 0.10 Benzonium chloride 0.10 Methyl salicylate 0.10 Saccharin 0.20 Perfume 0.25 Herbal extract 1.00 Water balance Total 100.00

[0060]

EFFECTS OF THE INVENTION According to the present invention, a highly safe anti-periodontal disease drug can be provided which is made from an extract of a crude drug which has been widely used as a component of Chinese herbs since ancient times. The anti-periodontal disease agent inhibits the growth of Porphyromonas gingivalis known as periodontopathic bacterium, and has an action of inhibiting collagenase produced by this bacterium, and therefore has an excellent preventive effect on periodontal disease and It can exert therapeutic effect. The crude drug extract used in the present invention has relatively little off-taste and off-flavor, and has excellent affinity (compatibility) with saliva,
It is widely applicable as an anti-periodontal disease agent in the form of oral composition.

Front page continuation (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 35/78 A61K 35/78 E H Q A61P 1/02 A61P 1/02 31/04 31/04 43/00 111 43 / 00 111 F-term (reference) 4B018 MD61 ME14 MF01 4C076 AA12 AA13 BB23 CC16 CC31 4C083 AA111 AA112 AA122 AB222 AB292 AB472 AC022 AC072 AC102 AC122 AC132 AC302 AC312 AC432 AC442 AC482 AC692 AC782 AC862 AD272 AD302 AD352 AD412 DD45 AD352 AD412 2253 AB33 AB38 AB43 AB52 AB57 AB65 AC03 AC04 AC05 AC06 AC11 AC13 BA08 CA03 MA17 MA57 NA06 NA07 NA10 NA14 ZA67 ZB35 ZC02

Claims (3)

[Claims] 1. A pine needle, a clove, a rosemary, a mulberry, a cherry bark,
A periodontopathic bacterium Porphyromonas gingivalis ( Porphyromona) containing an extract of at least one crude drug selected from the group consisting of beetle, Chinese cabbage, and Chinese citrus
Growth inhibitory effect of s gingivalis), as well as characterized by having an inhibitory effect of the P. gingivalis production collagenase, anti-periodontal disease agents. 2. The anti-periodontal disease medicine according to claim 1, wherein the crude drug extract is used as a flow extract in the case of mulberry, scallop, bark or Chinese cabbage, and as a tincture in the case of mulberry. . 3. A composition for oral cavity containing the anti-periodontal disease drug according to claim 1.