KR20160061852A - Oral composition containing both metal chelating agent and isopropylmethylphenol - Google Patents

Abstract

The present invention relates to an oral composition comprising a sequestering agent and isopropylmethylphenol as an active ingredient. The oral composition has significant effects in removing a biofilm and inhibiting the generation of the biofilm, which is a main cause of the corrosion of the teeth, tartar formation, and gum diseases. In addition, the oral composition exhibits effects in effectively maintaining and improving oral health by preventing and/or alleviating the gum diseases.

Description

[0001] The present invention relates to an oral composition containing both metal chelating agents and isopropylmethylphenol,

The present invention relates to an oral composition having an effect of suppressing the generation and / or elimination of biofilm and an effect of preventing and / or improving gum disease.

Oral health or normal function and condition is very important to the daily life of all human beings and severely hinders the quality of life in the event of an anomaly. The most significant factor affecting the oral health factor is tooth decay or tooth decay, gum disease, or periodontal disease, the root cause of which is biofilm formed by pathogens living in the mouth . When these pathogens are not adhered to the surface of the oral cavity, they are present in a solution such as saliva and can be easily removed together with toothpaste and beverage intake, so that there is little possibility of causing diseases in the oral cavity. However, since these pathogens are attached to the surface of the oral cavity for effective survival, biofilms are formed. Once biofilms are formed, the defense against external physical and chemical stimuli is remarkably increased. Therefore, It is difficult to remove by the method. When left untreated, the biofilm becomes thicker and stronger, forming tartar, becoming a habitat for many bacteria and causing various oral diseases. Physical methods such as scaling in dentistry have been recommended as a representative method to prevent such a process, and the effect has been verified. However, due to the hassle of dental visits, fears, and economic reasons, in most cases they are not adequately managed. There is a limit to the removal of biofilm and calculus by brushing, and many people are exposed to oral diseases. Accordingly, products containing ingredients for sterilizing cavities and periodontal bacteria such as chlorohexidine, cetyl pyridinium chloride, and triclosan have been developed and popularized. However, these synthetic antibiotics not only stimulate the mucous membranes in the oral cavity, but also cause the destruction of normal bacteria, thereby increasing resistance to oral pathogens, and adverse effects on the human body, such as tooth coloring and taste deterioration. Chlorohexidine, a typical antimicrobial used in oral cleansers, has been shown to exhibit shock symptoms, particularly when oral wounds are present. For example, Thymol, Eucalyptol, Menthol, Epigallocatechin gallate (EGCG), Xylitol and the like have been used in recent years. However, the effect is limited.

Streptococcus strains that are present at the bottom of the biofilm form lactic acid by using the sugar present in the oral cavity, and this lactic acid corrodes the enamel of the tooth to cause tooth decay. When the plaque is developed, P. gingivalis, which is present in the gums, generates irritating compounds and causes inflammation of the gum tissue.

According to the literature (Rosan et al., Microbes and Infection 2000, 2: 1599-1607), the formation of a biofilm involves an initial attachment step in which bacteria attach to the oral tissue surface, Co-adhesion < / RTI > The first step occurs over a period of about one week, almost entirely with Streptococcus strains. The second stage occurs over a period of several weeks and can involve more than 700 species of bacteria, but it is known to be mainly involved with P. gingivalis . It is also known that the presence of specific proteins mediating adhesion in both the initial adhesion step and the mutual adhesion step enables the formation of a biofilm. Therefore, the effect of the existing antibacterial component is limited because the antibacterial component is mainly used to remove only the bacteria present in the three-dimensional solution, while the adhesion step can not be effectively prevented. In the case of the biofilm already formed, And only temporary effects are shown. Therefore, a high concentration or an antimicrobial substance having high toxicity is required, which causes disadvantages of increased toxicity to human body, loss of taste, and increased resistance to bacteria. Therefore, as a product using a conventional ingredient, it is not only impossible for a general person to sufficiently prevent and remove the production of biofilm by a conventional method (such as use of a mouthwash and a mouthwash for 1-2 times a day). It is difficult to pursue oral health maintenance and improvement economically, conveniently, fundamentally, and safely because of the side effects.

Isopropylmethylphenol is a non-ionic fungicide that has attracted attention as a periodontal pathogenic fungicide. As a technique for preventing oral diseases by using isopropylmethylphenol so far, it has been described that when isopropylmethylphenol is dissolved in a low-concentration polyoxyethylene hydrogenated castor oil, it penetrates into a biofilm. However, Japanese Patent Application Laid-Open No. 62-24010 When using isopropylmethylphenol alone or in combination with other natural products, the cause of periodontal disease (periodontal disease) is actually caused by the use of isopropylmethylphenol alone or in combination with other natural products. It is difficult to penetrate into the inside of the biofilm, so that it is difficult to use the composition as an oral composition.

 Rosan et al., Microbes and Inf 2000, 2: 1599-1607

Accordingly, a problem to be solved by the present invention is to provide a method for effectively inhibiting and / or eliminating biofilm formation by bacteria, which is a key element in maintenance and improvement of oral health, And to provide an oral composition that exhibits a gum disease-improving function and the like.

In order to solve the above problems, the present invention provides an oral composition for suppressing or eliminating the occurrence of a biofilm comprising a metal ion sequestering agent and isopropylmethylphenol as an active ingredient.

The present inventors not only have an antimicrobial effect against bacteria floating in the oral cavity but also can prevent the formation of a biofilm initiated by attachment of bacteria to oral tissues and penetrate into the inside of the formed biofilm, Or composition. As a result, when isopropylmethylphenol and a sequestering agent are used together as an active ingredient, the sequestering agent remarkably lowers the defense against the physicochemical stimuli outside the biofilm, loosens the structure of the biofilm, and isopropylmethylphenol It has been found that biofilm penetrates deeper into the biofilm, thereby increasing the inhibition and elimination effect of biofilm, exhibiting excellent biofilm inhibition and removal effects at low concentrations, and exhibiting antimicrobial activity. The present invention has been accomplished by ascertaining the excellent practical value thereof.

In the present invention, the term 'bio-film' refers to a structure in which bacteria adhere to oral tissues and bacteria are further bound to bacteria attached thereto. The 'oral tissues' functionally function as digesting food Refers to a tissue in charge of a part, and includes hard tissues such as hard palate, teeth, alveolar bone, and cementum as hard tissues, and soft tissues such as gingiva, buccal mucosa, study dogs, tongue and the like. The term " attachment " means that the bacteria introduced into the oral tissues attach to the oral tissues. Among the bacteria forming the biofilm, bacteria that are involved in attachment to the oral tissues include, for example, bacteria belonging to the genus Streptococcus, or Actinomyces, Porphyromonas gingivalis , , inter-media presentation Bo telra (Prevotella intermedia), frame beam telra upgrade your sense (Prevotella nigrescens , Fusobacterium nucleatum , Serratia < RTI ID = 0.0 > marcescens), methyl tumefaciens (Methylobacterium) genus Pseudomonas (Pseudomonas), A janto Pseudomonas (Xanthomonas) genus Corynebacterium (Corynebacterium) genus and Bacillus (Although the bacteria such as Bacillus), A is not limited thereto.

The oral composition according to the present invention is not only effective in removing the produced biofilm, but also inhibits the attachment of bacteria to the surface of the oral tissues, thereby restraining the production of the biofilm.

In the present invention, isopropylmethylphenol is expected to penetrate into the inside of the biofilm when the structure of the biofilm is loosened by the sequestering agent to increase the effect of inhibiting and removing the biofilm and to have an excellent antimicrobial activity However, the present invention is not limited to this theory. The oral composition of the present invention has an effect of inhibiting the generation or elimination of the biofilm formed by the bacteria. The bacteria may preferably be homogenous causing gum disease and include, for example, Actinobacillus actinomycetemcomitans , Porphyromonas japonis var. gingivalis ), Tanerella forsythia (conventional Bacteriods forsythus ), Prevotella intermedia intermedia , Treponema denticola , Fusobacterium nucleatum , Fusobacterium alocis, Micromonas micros (conventional Peptostreptococcus micros )), Eikenella corrodens), or tired bakteo cam selector switch (Campylobacter rectus , and the like.

The oral composition capable of inhibiting the biofilm formation using the oral composition of the present invention has an IC ₅₀ concentration of 20 μg / ml or less, preferably 10 μg / ml or less, more preferably 7 μg / ml or less . In addition, the oral composition capable of removing the biofilm produced using the oral composition of the present invention has an IC ₅₀ concentration of 17 μg / ml or less, preferably 10 μg / ml or less, more preferably 7 μg / Lt; / RTI >

The oral composition of the present invention further has an effect of preventing and / or improving gum disease. The periodontal disease (periodontal disease) can include gingivitis and periodontitis, and can be preferably gingivitis.

The oral composition of the present invention comprises a metal ion sequestering agent and isopropylmethylphenol as an active ingredient, and the weight ratio of the metal ion sequestering agent and isopropylmethylphenol is 100: 1 to 1:10, preferably 10: 1: 5, more preferably 4: 1 to 1: 1. The oral composition outside the weight ratio range can not sufficiently exert the effect of suppressing or eliminating the biofilm formation.

In the present invention, the sequestering agent may contain 0.1 to 10% by weight, preferably 0.5 to 4% by weight, more preferably 0.5 to 2% by weight based on the total weight of the oral composition. If the amount is less than 0.1% by weight, the ability to inhibit dental calculus formation is weak. If the amount is more than 10% by weight, the feeling of use such as taste during tooth brushing may be poor and irritation may be caused.

The oral composition of the present invention may contain 0.01 to 1% by weight, preferably 0.03 to 0.5% by weight, based on the total weight of the composition of isopropylmethylphenol. When the amount is less than 0.01% by weight, no antibacterial activity is exhibited. If it exceeds 1% by weight, oral stimulation and stability are not preferable.

In the present invention, the metal ion sequestering agent refers to a compound that binds to a metal ion in an aqueous solution to form a soluble complex salt, thereby preventing the metal ion from causing precipitation by another reagent. In the oral composition of the present invention, the sequestering agent is a substance that inhibits the formation of calculus by chelating metal ions which have an important influence on the formation of calculus. Phosphoric acid-based compounds are preferable, for example, sodium phosphate, Monosodium phosphate, Disodium phosphate, Trisodium phosphate, Sodium triphosphate, Sodium hexametaphosphate, Tetrasodium pyrophosphate, Tetrasodium pyrophosphate, , And sodium acid pyrophosphate, or a mixture of two or more thereof, but is not limited thereto, more preferably tetrasodium pyrophosphate (Tetrasodium pyrophosphate) It does not. When such a phosphate compound is used in combination with isopropylmethylphenol, it is expected that the biofilm penetration can be promoted by lowering the biofilm structure significantly by lowering the protection against physicochemical stimulation outside the biofilm even at a low concentration , The present invention is not limited to these contents.

The oral composition according to the present invention may be formulated as a wetting agent, an abrasive, a pharmacological agent, a sweetener, a pH adjusting agent, an antiseptic agent, a binder, a flavoring agent, a foaming agent or the like for the purpose of proper formulation and formulation stability, , Or purified water, and the like, but the present invention is not limited thereto.

The wetting agent may be, for example, but not limited to, concentrated glycerin, glycerin, sorbitol aqueous solution, amorphous sorbitol aqueous solution, polyethylene glycols or propylene glycol, 70% by weight.

The abrasive includes, but is not limited to, precipitated silica, silica gel, zirconium silicate, calcium monohydrogenphosphate, calcium monohydrogenphosphate anhydrous, hydrous alumina, light calcium carbonate, heavy calcium carbonate, calcium pyrophosphate, insoluble metaphosphate Or aluminum silicate may be used. The amount of the abrasive to be used may generally be 1 to 60% by weight based on the total weight of the oral composition, but is not limited thereto.

Such medicaments include, but are not limited to, sodium fluoride, sodium fluorophosphate, sodium fluoride, tin fluoride, chlorohexidine, allantoin chlorohydroxy aluminate, aminocaproic acid, zinc chloride, pyridoxine hydrochloride, Tocopherol, enzymes and the like, or a mixture of two or more thereof.

For example, saccharin sodium, xylitol, erythritol, or aspartame may be used as the sweetener. The amount of the sweetener may be generally 0.05 to 0.5% by weight based on the total weight of the oral composition. It is not limited.

Examples of the pH adjuster include, but are not limited to, sodium phosphate, disodium phosphate, citric acid, triethanolamine, and the like.

Examples of the preservative include, but are not limited to, benzoic acid, methylparaben, propylparaben, sodium benzoate, and the like.

Examples of the binder include, but are not limited to, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, guar gum, pectin, polyvinylpyrrolidone, carboxyvinyl polymer, alginic acid Sodium, laponite, carbomer, carrageenan, xanthan gum, or alginates. The amount of such a binder to be used is generally 0.1 to 3% by weight, preferably 0.5 to 2% by weight based on the total weight of the oral composition, but is not limited thereto.

Examples of the fragrance include, but are not limited to, peppermint oil, spearmint oil, menthol, etc., alone or in combination.

Examples of the foaming agent include, but are not limited to, anionic surfactants such as sodium alkylsulfate and sodium laurylsulfate, copolymers of polyoxyethylene polyoxypropylene (non-ionic surfactant) (poloxamer), polyoxyethylene hydrogenated castor oil , Polyoxyethylene sorbitan fatty acid esters, and the like. The amount of the foaming agent to be used is generally 0.5 to 5% by weight, preferably 0.5 to 3.5% by weight based on the total weight of the oral composition, but is not limited thereto.

The oral composition of the present invention may also contain enzymes such as dextrinase as other additives.

The oral composition of the present invention may contain, in addition to the active ingredient, the additive, a residual amount of water, preferably purified water.

The oral composition according to the present invention may have formulations such as, for example, dentifrices, mouthwashes, sprays, mouthwashes, gums, candies, mouthwashes, tooth whitening agents, Any formulation that is likely to come into contact with the oral tissue after ingestion may be included without limitation and may be formulated by conventional means known to those of ordinary skill in the art.

More specifically, the present invention provides a toothpaste comprising a metal ion sequestering agent and isopropylmethylphenol as an active ingredient.

In the toothpaste of the present invention, the sequestering agent is preferably a phosphate compound, for example, sodium phosphate, monosodium phosphate, disodium phosphate, trisodium phosphate, One selected from the group consisting of sodium triphosphate, sodium hexametaphosphate, tetrasodium pyrophosphate, and sodium acid pyrophosphate, or a mixture of two or more thereof, But is not limited thereto. More preferably tetrasodium pyrophosphate, but is not limited thereto.

The dentifrice of the present invention has isopropylmethylphenol together with a sequestering agent to inhibit and / or eliminate biofilm formation, oral hygiene enhancement, and prevention and / or improvement of gum disease, even at a low concentration.

The oral composition of the present invention is excellent in suppressing the formation and / or elimination of biofilm, which is a major cause of tooth corrosion, dental calculus and gum disease by containing a sequestering agent and isopropylmethylphenol as active ingredients simultaneously , Exhibits the prevention and / or therapeutic effect of the gum disease, and provides a safe oral health maintenance and improvement effect to the human body.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples. However, the embodiments and examples according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the above-described embodiments and experiments. The embodiments and experimental examples of the present invention are provided to enable those skilled in the art to more fully understand the present invention.

Manufacturing example

The dentifrice compositions of Examples 1 to 6 and Comparative Examples 1 to 6 were prepared with the components and composition ratios shown in Table 1 below.

Powder components such as a binder and a sweetener were dispersed in a wetting agent, and purified water was added thereto, followed by primary mixing in a mixer, followed by addition of an abrasive, sodium chloride and bamboo salt, and secondary mixing. Finally, a foam stabilizer, a stabilizer, a perfume and the like were added and mixed in tertiary to prepare a dentifrice composition with the components and composition ratios shown in Table 1 below.

Experimental Example 1: Prevention of biofilm formation

The biofilm generation preventive effect is as important as the effect of inhibiting the biofilm formation by the composition prepared in the above Examples and Comparative Examples. Therefore, the composition was diluted with distilled water and used. Artificial saliva was prepared by diluting 1% type mucin (porcine stomach, Sigma-Aldrich) in the binding buffer and sterilized at 121 ° C for 15 minutes.

Streptococcus mutans (ATCC25275), Sts. Sanguis ATCC 10556, and Actinomyces viscosus KCCM 12074 were used as the strains for causing gum diseases. These strains were inoculated A multi-species inoculation solution was prepared. More specifically, each of the cultured bacteria was separated through a centrifuge (4500 rpm, 5 minutes) and suspended in PBS (phosphate-buffered saline, pH 7.2) at a concentration of 1 × 10 ⁶ CFU / ml. The inoculated cell solution contained the same concentration of each bacterium. Rukayadi and Hwang's method was used to measure the biofilm formation inhibitory activity of the compositions. More specifically, a sample of 0.5 to 50 占 퐂 / ml was added to each well of a 96-well polystyrene microplate and cultured at room temperature for 3 hours using a shaker, followed by drying in the air. 20 μl of the bacterial inoculum was added to a 96-well plate coated with the sample, and then the culture was added to a total volume of 200 μl (final concentration 1 × 10 ⁵ CFU / ml) and cultured at 37 ° C. for 24 hours. After the remaining culture was removed, cells that did not form the remaining biofilm were washed with 200 μl of 50 mM PBS. Cells formed with biofilm were stained with a 0.4% crystal violet solution for 30 minutes, and then the remaining solution was thoroughly washed with distilled water. The colored cells were dissolved in 200 μl of 90% ethanol, and the amount thereof was measured using absorbance (596 nm). The biofilm inhibitory effect of this sample was measured using the following formula (1), and the results are shown in Table 2 below.

[Equation 1]

(%) = (1 - absorbance of the cell coated with the sample / absorbance of the control cell) × 100

As a control, cells not coated with the sample were used, and a concentration (IC ₅₀ ) showing a 50% preventive effect was determined.

sample Biofilm generation 50% inhibitory concentration (IC ₅₀ , 占 퐂 / ml) sample Biofilm generation 50% inhibitory concentration (IC ₅₀ , 占 퐂 / ml) Example 1 6.1 Comparative Example 1 > 50 Example 2 3.5 Comparative Example 2 > 50 Example 3 4.3 Comparative Example 3 27 Example 4 3.1 Comparative Example 4 26 Example 5 3.0 Comparative Example 5 26 Example 6 2.2 Comparative Example 6 20

Experimental Example 2: Evaluation of biofilm removal effect

Effective removal of biofilms already formed in the mouth is just as important as inhibiting the production in improving oral health. Therefore, the biofilm removal effect of the composition prepared above was measured. To measure the bacterial film removal effect on the prepared composition, various bacterial biofilms were coated on a 96-well plate by the method of Sepanovic as follows. 200 쨉 l of artificial needle was added to each plate, incubated at room temperature for 3 hours with gentle shaking, the remaining unattached artificial needle was removed, and the plate was air-dried. 20 [mu] l of the bacterial inoculum was added to the plate and cultured in a BHI culture medium containing 3% sucrose at 37 [deg.] C for 24 hours to form a biofilm. After the remaining culture was removed, the remaining cells without biofilm were washed with 200 μl of 50 mM PBS. Each cell was treated with a test substance or a comparative sample at a concentration of 0.5 to 50 μg / ml and cultured for 1 hour. Cells formed with biofilm were stained with a 0.4% crystal violet solution for 30 minutes, and then the remaining solution was thoroughly washed with distilled water. The colored cells were dissolved in 200 μl of 95% ethanol and then measured using absorbance (596 nm). The biofilm removal activity of each sample was determined by comparing absorbance before and after treatment.

The biofilm removal effect was calculated by the following equation (2), and the concentration (IC ₅₀ ) showing the 50% removal effect was determined and shown in Table 3 below.

&Quot; (2) "

(%) = (1 - absorbance of sample / absorbance of cell not treated sample) x 100

sample Biofilm production 50% removal concentration (IC ₅₀ , ug / ml) sample Biofilm production 50% removal concentration
(IC ₅₀ , [mu] g / ml) Example 1 6.0 Comparative Example 1 > 50 Example 2 4.3 Comparative Example 2 > 50 Example 3 3.1 Comparative Example 3 39 Example 4 2.2 Comparative Example 4 32 Example 5 2.9 Comparative Example 5 28 Example 6 1.8 Comparative Example 6 17

EXPERIMENTAL EXAMPLE 3: Clinical Experiment on Dental Gum Disease Inhibition of Dental Composition

1) Subjects to be tested

Subjects were divided into 10 groups according to their gender, from 30 to 50 years of age. The subjects were divided into groups of 120 subjects. Clinical experiments on the effect of treating toothpaste (prepared in Examples 1 to 6) and comparative toothpaste (prepared in Comparative Examples 1 to 6) according to the present invention were carried out in the following manner.

2) Experimental method

The subjects were divided into two groups: the experimental group and the comparative group. The subjects were instructed to use three times a day before sleeping after 2 hours after the meal, and the initial gingival index was scored by subjecting the teeth to a denture base. After 3 months, oral examination was performed to check gingival index. The gingival index was measured by inserting a periodontal probe into the gingival sulcus and burning the circumference of each tooth without applying any force. After 30 seconds, the state of bleeding was measured. The scores were recorded and the results were obtained.

score Contents 0 point No bleeding state 1 point Normal bleeding state 2 points Hemorrhage 3 points Triangle Bleeding 4 points Gingival hemorrhage

Table 1 shows the results of the clinical tests for treating dental inflammation with the dentifrice compositions (Examples 1 to 6) and the comparative compositions (Comparative Examples 1 to 6) according to the present invention.

division Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Early 1.31 1.35 1.21 1.29 1.32 1.22 1.24 1.25 1.31 1.22 1.32 1.19 1 week 1.28 1.26 1.23 1.20 1.22 1.17 1.35 1.38 1.36 1.34 1.41 1.27 1 month 1.22 1.20 1.21 1.15 1.20 1.14 1.43 1.52 1.49 2.52 1.62 1.79 3 months 1.18 1.09 1.01 1.02 1.13 0.91 2.34 2.12 2.73 2.95 3.01 2.89

As can be seen from the above clinical test results, the dentifrice compositions of Comparative Examples 1 to 6 had little or no inhibitory effect on gingival inflammation, and the dentifrice compositions of Examples 1 to 6 had gingival inflammation The treatment effect was excellent.

According to the present invention, the dentifrice composition containing a metal ion sequestrant and isopropylmethylphenol according to the present invention can prevent the metal ion blocking agent from significantly protecting the biofilm against physicochemical stimuli from the outside, It is judged that it is excellent in effectively maintaining and improving oral health by increasing the suppression and / or elimination effect of film formation and by eliminating bad breath and preventing and / or improving gum disease.

Claims (11)

The oral composition for suppressing or eliminating the occurrence of a biofilm, which comprises a metal ion sequestering agent and isopropylmethylphenol as an active ingredient. The method according to claim 1,
Wherein the weight ratio of the metal ion sequestrant and the isopropylmethyl phenol is 100: 1 to 1:10. The method according to claim 1,
Wherein the oral composition has an effect of preventing or improving gum disease. The method according to claim 1,
Wherein the isopropylmethyl phenol is 0.01 to 1% by weight based on the total weight of the oral composition. The method according to claim 1,
Wherein the metal ion sequestering agent is 0.1 to 10% by weight based on the total weight of the oral composition. The method according to claim 1,
The metal ion sequestrant may be selected from the group consisting of sodium phosphate, monosodium phosphate, trisodium phosphate, sodium tripolyphosphate, sodium hexamethaphosphate, tetrasodium pyrophosphate Tetrasodium pyrophosphate, and sodium acid pyrophosphate, or a mixture of two or more thereof. The oral composition according to claim 1, wherein the composition is at least one selected from the group consisting of Tetrasodium pyrophosphate and Sodium acid pyrophosphate. The method according to claim 6,
Wherein the metal ion sequestering agent is tetrasodium pyrophosphate, sodium acid pyrophosphate, or a mixture thereof. The oral composition according to claim 1, wherein the metal ion sequestrant is tetrasodium pyrophosphate, sodium acid pyrophosphate, or a mixture thereof. The method according to claim 1,
Wherein the oral composition inhibits the attachment of bacteria to the surface of the oral tissues. 9. The method of claim 8,
Wherein the bacteria are causative agents of gum disease. 10. The method of claim 9,
Actinobacillus actinomycetemcomitans , Porphyromonas gingivalis , Tanerella forsythia , Prevotella intermedia , Pseudomonas aeruginosa , and the like are examples of the causative bacteria of the periodontal disease. Pho Tre denti Cinema cola (Treponema denticola), Fu Te earthy Solarium press Hinckley Atum (Fusobacterium nucleatum), Fu Te earthy Solarium Alor system (Fusobacterium alocis , Micromonas micros , Eikenella < RTI ID = 0.0 > corrodens , or Campylobacter rectus . < RTI ID = 0.0 > 11. < / RTI > The method according to claim 1,
Wherein the oral composition promotes penetration of the biofilm produced.