KR20220096399A - Composition for Inhibiting Biofilm Formation Comprising Extracts of Coptis chinensis - Google Patents

Abstract

The present invention relates to a composition for inhibiting biofilm formation comprising an extract of Coptis japonica as an active ingredient. The extract of Coptis japonica of the present invention is non-cytotoxic, inhibits the activity of glucosyltransferase enzyme secreted by oral microorganisms such as Streptococcus mutans strains, and thus can effectively inhibit a biofilm formed by oral microorganisms such as Streptococcus mutans strains, so that it is possible to be usefully used for preventing or treating oral diseases caused by bacterial biofilm formation.

Description

Composition for Inhibiting Biofilm Formation Comprising Extracts of Coptis chinensis

The present invention relates to a composition for inhibiting biofilm formation, including an extract of ginseng lily, and a composition for preventing, improving or treating oral diseases, including an extract of ginseng lily.

A biofilm is also called a biofilm, and refers to a state in which microorganisms produce polysaccharides around cells and aggregate with adjacent microorganisms as a medium to form a film on a solid or biological surface.

It is reported that the microorganisms forming the biofilm are more than 1,000 times more resistant to antibiotics than the microorganisms in the suspended state, and the biofilm formation is caused by bacterial endocarditis, dental caries, and chronic sinusitis. , food poisoning, it is well known that it plays an important role in the pathogenesis of various diseases such as pneumonia (Non-Patent Document 1).

On the other hand, dental caries (cavities) is caused by Streptococcus mutans (S. mutans) attached to the tooth surface in the oral cavity, and the S. mutans strain secretes a glucosyltransferase enzyme. The secreted glucosyltransferase enzyme decomposes sucrose into glucose and fructose, and uses the glucose to synthesize glucan, a polysaccharide. The synthesized glucan helps the attachment of other microorganisms, and as a result, a lot of glucan is formed on the tooth surface, which increases the volume of plaque, a type of biofilm. S. mutans strains attached to teeth by forming biofilms have resistance to external physical and chemical treatments for hygiene, so they can stay in the oral cavity for a long time. As such, S. mutans strains that have not been completely removed continue to act, causing chronic diseases and complications in the oral cavity.

Therefore, when the activity of glucosyltransferase is inhibited, it can be seen that the formation of a biofilm is effectively inhibited.

In addition, since biofilms cause diseases such as dental caries or intractable infections in living tissues, it is necessary to effectively inhibit the formation of biofilms to prevent the onset of diseases, for example, to prevent the accumulation of microorganisms by interfering with polysaccharide synthesis. something is needed

Dental treatment agents currently used in clinical practice are known to exhibit various side effects. Calcium hydroxide, chlorhexidine, and triple compound antibiotics used as representative dental treatments show side effects such as tissue necrosis, sensory abnormality, tooth discoloration, and allergic reaction. In addition, chemical methods such as acid/alkali wash, chlorine, and peracid sanitizer pose a risk of corrosion when used on metal materials. In particular, it has been reported that chlorine-based disinfectants frequently used in sterilization treatment generate carcinogens such as trihalomethanes. On the other hand, after sterilization, a large amount of washing water is required in the washing process, and by reusing the washing water, there may be a problem that pathogenic microorganisms are recontaminated in the sterilized and sterilized food processing equipment.

As such, dental treatment agents used for biofilm removal have limitations in that they exhibit side effects on the human body, and accordingly, there is a need to develop a new biocompatible dental treatment agent capable of efficiently controlling biofilms without side effects.

In addition, as natural products with fewer side effects and improved therapeutic effects have recently received attention, development of natural extracts for the purpose of removing biofilms is necessary, but research on natural extracts effective for biofilm removal is still insufficient. .

Under this background, the present inventors have studied the effects of treatment or prevention of oral diseases with various plant extracts, and while the extracts of yellow lilies effectively inhibit the formation of biofilms, block the activity of glucosyltransferase to prevent the formation of biofilms. It was confirmed that it is effective in fundamentally blocking, and the present invention has been completed.

Korean Patent Registration No. 10-1506858 Korean Patent Registration No. 10-1929565 Korean Patent Publication No. 10-2020-0137316

http://www.intron.co.kr/sub/technologies/biofilm.php

Therefore, a main object of the present invention is to provide a composition for inhibiting biofilm formation comprising an extract of Coptis chinensis as an active ingredient.

Another object of the present invention is to provide a composition for preventing or improving oral diseases, comprising an extract of Coptis chinensis as an active ingredient.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, the present invention provides a composition for inhibiting biofilm (biofilm) formation comprising an extract of Coptis chinensis as an active ingredient.

The present inventors suppressed the formation of biofilms and conducted experiments for many years to search for substances derived from natural materials that are effective in preventing or treating oral diseases such as dental caries, and the oral cavity with hundreds of various plant extracts. The effect on the disease was verified. As a result, it was confirmed that the yellow lotus extract effectively inhibits the formation of a biofilm, and blocks the activity of glucosyltransferase to fundamentally block the formation of the biofilm, thereby completing the present disease.

The composition of the present invention is safe without side effects even when applied to the human body, because the composition contains, as an active ingredient, a safe natural plant material-derived extract from a plant material without side effects.

"Hwangryeon ( Coptis chinensis )" of the present invention means an evergreen perennial of the dicotyledonous plant Heterinus Heterenae. Yellow lotus is known to have effects such as strengthening blood pressure, preventing digestion, preventing food poisoning and diarrhea, and detoxifying. However, there is no known conventionally about the effect of inhibiting the formation of a biofilm by microorganisms.

As used in the present invention, the term "extract" refers to an extract obtained by extraction treatment of rhododendron, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a prepared or purified product of the extract, or a mixture thereof, such as an extract It includes extracts of all formulations that can be formed by themselves and using extracts. The extract of the present invention may be prepared and used in the form of a dry powder after extraction. In the extraction of the yellow lily, the method of extracting the extract is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, reflux extraction, and the like, and these may be performed alone or in combination of two or more extraction methods.

In the present invention, the type of the extraction solvent used for extracting the rhododendron is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent include water; C1-C4 lower alcohols, such as methanol, ethanol, propyl alcohol, and butyl alcohol; polyhydric alcohols such as glycerin, butylene glycol and propylene glycol; and hydrocarbon solvents such as methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, and dichloromethane; Alternatively, a mixture thereof may be used, and preferably, water, lower alcohol, 1,3-butylene glycol, and ethyl acetate may be used alone or in a mixture of two or more.

In the present invention, the extract extracted with hot water or chilled extract is filtered to remove floating solid particles, for example, using nylon or the like to filter the particles, or after filtration using a freeze filtration method, etc. It can be used by drying it using spray drying or the like.

As used herein, the term “fraction” refers to a result obtained by performing fractionation in order to separate a specific component or a specific component group from a mixture including various components.

A non-limiting example of the fractionation method may include a method of obtaining a fraction from the extract by treating the extract obtained by extracting yellow lilies with a predetermined solvent. The kind of solvent used to obtain the fraction in the present invention is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the fractionation solvent include polar solvents such as water and alcohol; and non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of two or more. When alcohol is used in the fractionation solvent, specifically C1 to C4 alcohol may be used.

The extract of yellow lotus of the present invention can be extracted from any one or more parts of the outpost, leaf, stem, and root of yellow lotus, but it is preferable to extract the root. In addition, the extract may be extracted from natural, hybrid or mutated plants, and may also be extracted from plant tissue culture.

In the present invention, the hwangryeon extract is effective in inhibiting biofilm formation itself.

As used herein, the term “biofilm (biofilm)” refers to a membrane-like structure formed by microorganisms, and has structural features consisting of interconnected microbial cell layers and microbial secretions. Microorganisms secrete enzymes that produce polysaccharides to the outside of cells to form water-soluble or insoluble polysaccharides from sugar substances present in the external environment, and when these insoluble polysaccharides are continuously accumulated, a thin biofilm in the form of a film is formed. The formed biofilm helps the aggregation between microorganisms, which can result in diseases such as dental caries.

According to one embodiment of the present invention, the biofilm is Streptococcus genus ( Streptococcus sp. ), Lactobacillus genus ( Lactobacillus sp. ), Actinobacillus genus ( Actinobacillus sp. ), Aggregatibacter sp. ), Porphyromonas sp. , Tannerella sp. , Treponema sp. , Prevotella sp. , and Fusobacterium sp. ) may be formed by one or more microorganisms selected from the group consisting of, but is not limited thereto.

In addition, the biofilm is Streptococcus mutans ( Streptococcus mutans ), Streptococcus salivarius , Streptococcus salivarius , Streptococcus gordonii ), Streptococcus gordonii ) ), Streptococcus pyogenes ( Streptococcus pyogenes ), Lactobacillus acidophilus ( Lactobacillus acidophilus ), Lactobacillus casei ( Lactobacillus casei ), Actinobacillus viscous sus ( Actinobacillus viscosus ), Aggregati bacillus ( Aggregatibacter actinomycetemcomitans ), Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola ), Prevotella intermedia , and fusobacterium Nucleatum ( Fusobacterium nucleatum ) It may be formed by a microorganism selected from the group consisting of, but is not limited thereto, and preferably, it may be formed by a Streptococcus mutans strain.

According to another aspect of the present invention, the present invention provides a pharmaceutical composition for preventing or treating oral diseases comprising an extract of Coptis chinensis as an active ingredient. The extract of the present invention is effective in inhibiting biofilm formation by itself, and is effective in treating and preventing oral diseases caused by the formation of a bacterial biofilm. Bacteria that form the bacterial biofilm causing the oral disease are the same as described above, and the description will be omitted here to avoid overly complicating the specification due to excessive description.

In the pharmaceutical composition for preventing or treating oral diseases of the present invention, a representative example of the oral microorganisms may include Streptococcus mutans , and oral disease is a biofilm caused by a Streptococcus mutans strain. It may be an oral disease caused by (biofilm) formation.

The Streptococcus mutans strain is an important causative bacterium that attaches to the tooth surface in the oral cavity to induce dental caries (cavities), and synthesizes a polysaccharide called glucan using glucose, and forms a biofilm with the generated glucan to form a biofilm. It has resistance to external physical and chemical treatment by attaching it to the

Since the extract of the present invention inhibits the activity of glucosyltransferase secreted by oral microorganisms such as Streptococcus mutans strain, and can effectively inhibit the biofilm formed by oral microorganisms such as Streptococcus mutans strain, It can be usefully used to effectively suppress dental caries, which can be caused by biofilm and plaque, and consequent stomatitis and bad breath.

Accordingly, in the pharmaceutical composition for preventing or treating oral disease of the present invention, the oral disease may be dental caries or stomatitis.

The pharmaceutical composition for preventing or treating oral diseases of the present invention may be in the form of a pharmaceutical composition comprising a pharmaceutically acceptable carrier. The pharmaceutical composition may be formulated in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. according to a conventional method, and it is more preferable that they are powders, tablets, capsules, and liquids. desirable. Such formulation may be performed by a method conventionally performed in the pharmaceutical field, and is preferably formulated according to each disease or added component using the method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA). can do.

The pharmaceutically acceptable carrier is lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil and the like.

Solid preparations for oral use include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient, for example, starch, calcium carbonate, sucrose, or lactose. ), gelatin, and the like, and lubricants such as magnesium stearate and talc. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, and the like, and may include water and diluents such as liquid paraffin, wetting agents, sweetening agents, fragrances, and preservatives.

In the oral composition of the present invention, in addition to the above formulations such as powders, tablets, capsules, etc., it may be formulated as, for example, a film, toothpaste, mouthwash, ointment, spray, dressing solution, coating agent, dental floss or periodontal sack.

In the pharmaceutical composition of the present invention, 0.1 to 50% by weight, preferably 1 to 20% by weight of the extract based on the total weight of the composition, the method of using the pharmaceutical composition for preventing or treating oral diseases and The content of the active ingredient can be appropriately adjusted according to the purpose of use.

The pharmaceutical composition of the present invention can be orally administered according to a desired method, and the dosage ranges depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate and severity of disease. is diverse

The daily dose of the extract of the present invention is about 0.1 to 500 mg/kg, preferably 50 to 200 mg/kg.

The pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery and drug treatment for the prevention and treatment of oral diseases, for example, caries prevention, periodontal disease prevention, gingivitis prevention, bad breath removal For the effects such as fluoride, zinc chloride, chlorhexidine, aminocaproic acid, tranexamic acid, cetylpyridium chloride, pyridoxine chloride, triclosan, tocopherol acetate, sodium monofluorophosphate, etc., including, but not limited to, these alone or a mixture of two or more.

According to another aspect of the present invention, the present invention provides a food composition for preventing or improving oral diseases comprising an extract of Coptis chinensis as an active ingredient.

The extract of the present invention has no cytotoxicity, is effective in inhibiting biofilm formation by itself, and is effective in preventing and improving oral diseases caused by the formation of bacterial biofilms, so for preventing or improving oral diseases It can be usefully used as a food composition. The effect on the prevention and improvement of oral diseases and the extract of Hwangryeon lily of the present invention is the same as described above. The food composition may be used in the form of a health functional food, but is not limited thereto.

The food composition of the present invention may be included in the form of a fraction or a processed product of Hwangryeon extract. In addition, the composition may include a food pharmaceutically acceptable food supplement additive in addition to the active ingredient.

In the present invention, "food supplement additive" refers to a component that can be added to food as an auxiliary, added to the manufacture of health functional food of each formulation, and can be appropriately selected and used by those skilled in the art. Examples of food supplement additives include various nutrients, vitamins, minerals (electrolytes), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents and fillers, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners , pH adjuster, stabilizer, preservative, glycerin, alcohol, carbonation agent used in carbonated beverages, etc., but the above examples are not limited to the type of food supplement additive of the present invention.

The food composition of the present invention may include a health functional food. In the present invention, "health functional food" refers to food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. using raw materials or ingredients useful for the human body. As used herein, the term "functional" refers to obtaining a useful effect for health purposes such as regulating nutrients or physiological action with respect to the structure and function of the human body, and specifically refers to the effect of preventing or improving oral diseases. The health functional food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and components commonly added in the art.

In addition, if the formulation of the health functional food is also recognized as a health functional food, it may be manufactured without limitation. The food composition of the present invention can be prepared in various types of dosage forms, and unlike general drugs, it has the advantage that there are no side effects that may occur when taking the drug for a long period of time by using an edible yellow lotus extract as a raw material, and it is effective in the action of oral microorganisms. By inhibiting the formation of a biofilm in the oral cavity, inhibiting the activity of glucosyltransferase, and through this, it has an excellent effect in improving oral diseases, so it can be taken as an adjuvant to enhance the therapeutic effect of oral diseases.

There is no limitation in the form that the health functional food of the present invention can take, and it may include all foods in a conventional sense, and may be used in combination with terms known in the art, such as functional food. In addition, the health functional food of the present invention can be prepared by mixing known additives with other suitable auxiliary ingredients that may be included in food according to the selection of those skilled in the art. Examples of foods that can be added include beverages, tea, drinks, alcoholic beverages, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, and vitamin complexes, and the like, and can be prepared by adding to juice, tea, jelly, juice, etc. prepared by using the extract according to the present invention as a main component. Also included are foods used as feed for animals.

Since the composition of the present invention is effective in preventing and improving oral diseases by itself, it can be directly used as a composition for preventing and improving oral diseases, and is used by mixing with other ingredients containing natural extracts effective for oral diseases It is expected that it will be possible to use it in the form of

The features and advantages of the present invention are summarized as follows:

(1) The present invention provides a composition for inhibiting the formation of a biofilm (biofilm) comprising an extract of H.

(2) The extract of the present invention has no cytotoxicity, inhibits the glucosyltransferase enzyme activity secreted by oral microorganisms such as Streptococcus mutans strains, and is a bio-formed by oral microorganisms such as Streptococcus mutans strains. Since the film can be effectively suppressed, it can be usefully used for preventing or treating oral diseases caused by the formation of a bacterial biofilm.

1 is a graph showing the change in the amount of biofilm production according to the treatment of hwangryeon extract.
Figure 2 is a graph showing the measurement of changes in glucosyltransferase enzyme activity according to the treatment of Hwangryun extract.

Hereinafter, the configuration of the present invention will be described in more detail with reference to examples, but the scope of the present invention is not limited to the embodiments disclosed below, but will be implemented in various different forms, and only these embodiments are It is provided so that the disclosure of the invention is complete, and to fully inform those of ordinary skill in the art to which the invention belongs, the scope of the invention, and the invention is only defined by the scope of the claims. In addition, the significance between the control group, the comparison group, and the experimental groups according to the experimental results described below was verified by One-Way ANOVA.

Example 1. Preparation of extracts of yellow lilies

200 ml of 70% ethanol was added to 20 g of yellow lily, respectively, and extracted under reflux for 3 hours in a water bath at 100 ° C. Thereafter, the extract was filtered using filter paper, and concentrated at 40° C. or less to use in the experiment.

Example 2. Inhibitory activity of biofilm formation of H. extracts

Streptococcus mutans (hereinafter referred to as “S. mutans”) strains were sold from the Microbial Bank of the National Academy of Agricultural Sciences (KACC) and cultured in BHI (Brain Heart Infusion medium, Bacto™, BD Biosciences) medium.

S. mutans strains were streaked on a BHI agar plate and then cultured at 37° C. for 2 days. A single colony was taken from the plate, inoculated into 5 ml of BHI broth, and stationary culture was performed at 37°C for 1 day.

100 μl of BHI medium containing 1% sugar was dispensed into a 96-well plate (SPL), and 1 μl of the yellow lily extract prepared in Example 1 was additionally dispensed. Next, the stationary cultured S. mutans strain was inoculated into each well at an OD600 of 0.05, and cultured at 37° C. for 24 hours. After 24 hours, the absorbance (optical density, OD; absorbance) was measured at OD595 to confirm the cell density of the S. mutans strain, and after removing the culture medium from the plate, it was gently washed 3 times with distilled water.

100 μl of a 1% crystal violet solution was dispensed into each well and the biofilm was stained at room temperature for 15 minutes. After 15 minutes, it was washed 3 times with distilled water, and 100 μl of 95% ethanol was added to elute the crystal violet and left for 15 minutes. Thereafter, the amount of the biofilm formed by measuring the absorbance at OD595 with a microplate reader was quantified and summarized in FIG. 1 .

Referring to FIG. 1, it was confirmed that the amount of biofilm was significantly reduced in the experimental group to which the hwangryeon extract was added, and 96.71% ( 31.3 μg/ml), 73.3% (62.5 μg/ml), 29% (125 μg/ml), 25% (250 μg/ml), and 11% (500 μg/ml) biofilm production was measured. .

Through the above experimental results, it was confirmed that the extract of the present invention has an excellent effect in inhibiting the biofilm produced by Streptococcus mutans.

Example 3. Glucosyltransferase Inhibitory Activity of Yellow Lotus Extract

3-1. Production and isolation of glucosyltransferase enzymes from S. mutans strains

Since the S. mutans strain secretes a glucosyltansferase (hereinafter referred to as “GTase”) enzyme to the outside of the cell, the GTase enzyme produced by the S. mutans strain was isolated by the following method.

First, a single colony was taken from the plate and the S. mutans strain was inoculated in 40 ml of BHI broth, and then cultured at 37° C. for 24 hours. After 24 hours, absorbance was measured at 600 nm with a spectrophotometer, and the S. mutans strain was inoculated so as to be 0.05 at OD600 in 1L of fresh BHI broth. S. mutans strain was cultured for 24 hours in fresh BHI broth to produce GTase enzyme.

After 24 hours, the culture medium was centrifuged at 1,500 x 10 g at 4 °C for 10 minutes to collect the supernatant containing the GTase enzyme. To precipitate the protein, the collected supernatant was mixed with 95% ethanol refrigerated (4°C) in a ratio of 1:1, and reacted in a refrigerator at 4°C for 24 hours. Next, the supernatant was removed by centrifugation at 1,500 x 10 g at 4 °C for 10 minutes, and only the precipitated protein was collected. The collected protein was dissolved again using 10 ml of 60 mM potassium phosphate buffer (pH 6.8), washed, and centrifuged under the same conditions as above. Thereafter, the supernatant was removed and the precipitate was again dissolved in 10 ml of 60 mM potassium phosphate buffer, then dispensed by 1 ml and stored at a temperature of -20°C.

3-2. Measurement of GTase Enzyme Activity Inhibiting Ability of Yellow Lotus Extract

Glucosyltransferase (GTase) decomposes sucrose into glucose and fructose in the oral cavity, and synthesizes a polysaccharide called glucan using glucose. The generated glucan helps the microbes to adhere to the tooth surface, and as a result, a lot of glucan is formed on the tooth surface to increase the volume of plaque, a type of biofilm. Therefore, when the activity of glucosyltransferase is inhibited, it can be seen that the formation of a biofilm is inhibited.

Using the GTase enzyme prepared in Example 3-1, the ability to inhibit the enzyme activity of the extract of yellow lily was measured.

Since GTase enzyme breaks down sugar into glucose and converts glucose to glucan, a 60 mM potassium phosphate buffer containing sugar (with 1.25% sugar and 0.025% NaN ₃ , pH 6.8) was used as a substrate for measuring the enzyme reaction. did. Specific enzyme reaction conditions are described in [Table 1] below, and the reaction was carried out at 37°C for 24 hours.

(Unit: μl) temperament GTase extract Distilled water menstruum Sum blank test group 800 0 50 100 0 1000 negative control 800 50 0 150 50 experimental group 800 50 50 100 0

After the reaction was completed, the glucan was released for 5 seconds using a sonicator. The supernatant was removed by centrifugation at 4°C for 10 minutes under 1,500 x 10g conditions, 200 μl of distilled water was added to the precipitate, and sonication was performed for 3 seconds using an ultrasonic grinder to release the precipitate again. .

200 μl of each was dispensed in a 96-well plate (SPL), and the amount of glucan produced was measured by measuring turbidity at absorbance 540 nm using a microplate reader, arranged.

Referring to FIG. 2 , it was confirmed that the amount of glucan produced was significantly reduced in the experimental group to which the Hwangryeon extract of the present invention was added, and 94.47 in the test group treated with the H. % (31.3㎍ / ㎖), 83.3% (62.5㎍ / ㎖), 50% (125㎍ / ㎖), 48% (250㎍ / ㎖), and 46% (500㎍ / ㎖) of glucan production amount was measured.

Through the above experimental results, it was confirmed that the extract of the present invention inhibits the activity of the glucosyltransferase (GTase) enzyme to reduce the production of glucan, thereby having an excellent effect in inhibiting the biofilm.

Claims (6)

A composition for inhibiting the formation of a biofilm comprising an extract of Coptis chinensis as an active ingredient. The method of claim 1,
The biofilm is a composition for inhibiting biofilm formation that is formed by Streptococcus mutans . A pharmaceutical composition for preventing or treating oral diseases comprising an extract of Coptis chinensis as an active ingredient. 4. The method of claim 3,
The oral disease is Streptococcus mutans ( Streptococcus mutans ) A pharmaceutical composition for preventing or treating oral diseases caused by biofilm formation. 4. The method of claim 3,
The oral disease is a pharmaceutical composition for preventing or treating oral disease that is dental caries or stomatitis. A food composition for preventing or improving oral diseases, comprising an extract of Coptis chinensis as an active ingredient.

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