JP7206302B2 - Composition for prevention or treatment of oral disease - Google Patents

Description

TECHNICAL FIELD The present invention relates to a composition for preventing or treating oral diseases, which contains a natural compound as an active ingredient, and more particularly, a medicament having an effect of preventing or improving dental caries, periodontal disease, toothache, hypersensitivity, and halitosis. It relates to quasi-product compositions. The present invention also relates to pharmaceutical compositions, food compositions and oral compositions containing natural compounds as active ingredients.

Healthy teeth are said to be one of the five good fortunes, and are an important factor that determines the quality of life. Among oral diseases, dental cavities (cavities) and periodontal disease (periodontal disease) are diseases with a high incidence rate worldwide, and cause pain, masticatory dysfunction, destruction of periodontal tissue, and bad breath. It is known to induce various clinical symptoms such as hyperesthesia, hyperesthesia, etc., and to be a major factor leading to tooth loss.

About 600 to 800 or more kinds of microorganisms are known to exist in the human oral cavity, and these microorganisms are controlled by enzymes such as lysozyme contained in saliva. However, an oral environment rich in nutrients and moisture provides favorable conditions for the growth of microorganisms, and the tongue and dental plaque are suitable habitats for microorganisms. Some of these microorganisms are opportunistic pathogens and cause diseases such as dental caries, periodontal disease, hypersensitivity (dentin hypersensitivity), and halitosis.

Antibacterial agents are used as a method of suppressing the growth of oral pathogens that live in dental plaque and cause caries, periodontal disease, bad breath, and hypersensitivity. Various antibacterial preparations, including antibacterial preparations, have been developed as inhibitors and therapeutic agents for dental caries, periodontal disease, pulpal and root-tip infections.

However, antibiotics cause systemic side effects in the human body, as well as the emergence of resistant bacteria and superinfection in the oral cavity, so they are difficult to use for a long time and are used only as therapeutic agents. There is Sanguinarine, Listerine, Peroxide, and Chlorhexidine are examples of antibacterial preparations used for mouthwash, but the effect of Sanguinarine on bacteria in the oral cavity is unknown. However, its therapeutic effect on periodontal disease is not only unknown, but it is also expensive. However, it has the drawback of causing tissue harm if used for a long period of time. Furthermore, in recent years, peroxides that have been added for whitening effect are toxic to bacteria, but at the same time they are toxic to human tissues, so not only are there safety problems, Some resistant strains may emerge. Furthermore, chlorhexidine is known to be the most excellent agent among conventional preparations as a preventive and therapeutic agent for periodontal disease as well as for suppressing plaque formation, but it induces tissue irritation, tissue discoloration and degeneration, Not only does it have the problem of having a particularly pungent taste and strong odor, but it can also induce bacterial superstition and is carcinogenic, so its use is restricted to pregnant women. It has the disadvantage that it cannot be used for a long period of time.

Furthermore, compounds artificially synthesized through chemical reactions may show cytotoxicity or cause side effects such as accumulation in the human body. There is a need for research into the pharmacological activity of natural compounds.

The present inventors have conducted extensive research to find natural materials that are free from such side effects and have excellent preventive and ameliorative effects on oral diseases such as dental caries, periodontal disease, toothache, hyperesthesia, and bad breath. . As a result, natural compounds that can be used safely and securely in the human body have an antibacterial effect against caries and periodontal disease-causing bacteria, an effect of alleviating toothache by suppressing PGE2, an effect of suppressing the onset of gingivitis, an effect of suppressing hypersensitivity, and an effect of removing halitosis. and completed quasi-drug compositions, pharmaceutical compositions, food compositions and oral compositions utilizing it.

An object of the present invention is to provide a quasi-drug composition for preventing or improving oral diseases, containing a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating oral diseases, which contains a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

A further object of the present invention is to provide a food composition for preventing or improving oral diseases, containing a natural compound or a food-acceptable salt thereof as an active ingredient.

A further object of the present invention is to provide an oral composition containing a natural compound or an acceptable salt thereof as an active ingredient.

A quasi-drug composition containing the natural compound of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient is excellent in preventing or improving oral disease. Specifically, the composition of the present invention has excellent antibacterial activity against caries- and periodontal-disease-inducing bacteria, inhibits pain and inflammation marker PGE2 in a concentration-dependent manner, inhibits the onset of gingivitis, and hyperesthesia symptoms. It has excellent inhibitory effect and bad breath removing effect, and is highly utilized as a quasi-drug composition for preventing or improving at least one oral disease selected from the group consisting of dental caries, periodontal disease, hypersensitivity and bad breath. Compositions containing the natural compounds of the present invention are also useful as pharmaceutical and food compositions.

In order to solve the above problems and achieve the above objects, one aspect of the present invention provides a quasi-drug composition for preventing or improving oral diseases, comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. offer things.

Another aspect of the present invention provides a pharmaceutical composition for preventing or treating oral diseases, comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

Yet another aspect of the present invention provides a food composition for preventing or improving oral diseases, containing a natural compound or a food-acceptable salt thereof as an active ingredient.

Yet another aspect of the present invention provides an oral composition comprising a natural compound or an acceptable salt thereof as an active ingredient.

The present invention provides a quasi-drug composition containing a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

The "natural compound" means a substance that is directly produced from living organisms such as microorganisms, plants, and animals and can be extracted, separated, or purified therefrom. Specific examples of the natural compound include albiflorin and astragaloside. Astragaloside I, Brassinolide, Eleutheroside E, Gentiopicrin, Gramine, Liensinine, Macranthoidin B, Neohesperidin Dihydrochalcone dihydrochalcone, Obacunone, Oxysophocarpine, Sclareolide, Sophoricoside, Sweroside, Synephrine, etc., but not limited thereto.

Albiflorin in the present invention is an organic compound represented by Chemical Formula ₁ , having a molecular formula of _C23H28O11 and a molecular weight of _408.4 .

The Astragaloside I in the present invention is an organic compound represented by Chemical Formula 2 and having a molecular formula of C ₄₅ H ₇₂ O ₁₆ and a molecular weight of 869.0.

The brassinolide in the present invention is an organic compound represented by Chemical Formula 3 and having a molecular formula of C ₂₈ H ₄₈ O ₆ and a molecular weight of 480.6.

The eleutheroside E in the present invention is an organic compound represented by Chemical Formula 4 and having a molecular formula of C ₃₄ H ₄₆ O ₁₈ and a molecular weight of 742.7.

The gentiopicrin in the present invention is an organic compound represented by Chemical Formula 5 and having a molecular formula of C ₁₆ H ₂₀ O ₉ and a molecular weight of 356.3.

The gramine in the present invention is an organic compound represented by Chemical Formula 6 and having a molecular formula of C ₁₁ H ₁₄ N ₂ and a molecular weight of 174.

Liensinine in the present invention is an organic compound represented by Chemical Formula ₇ and having a molecular _formula of _C37H42N2O6 and a molecular weight of _610.7 .

The Macranthoidin B in the present invention is an organic compound represented by Chemical Formula 8 and having a molecular formula of C ₆₅ H ₁₀₆ O ₃₂ and a molecular weight of 1399.5.

The neohesperidin dihydrochalcone in the present invention is an organic compound represented by Chemical Formula ₉ and having a molecular formula of _C28H36O15 and a molecular weight of _612.5 .

Obacunone in the present invention is an organic compound represented by Chemical Formula 10 and having a molecular formula of C ₂₅ H ₃₀ O ₇ and a molecular weight of 455.

The Oxysophocarpine in the present invention is an organic compound represented by Chemical Formula ₁₁ , having a molecular _formula of _C15H22N2O2 and a molecular weight of _262.4 .

The sclareolide in the present invention is an organic compound represented by Chemical Formula 12, having a molecular formula of C ₁₆ H ₂₆ O ₂ and a molecular weight of 250.3.

The sophoricoside in the present invention is an organic compound represented by Chemical Formula 13, having a molecular formula of C ₂₁ H ₂₀ O ₁₀ and a molecular weight of 432.

The sweroside in the present invention is an organic compound represented by Chemical Formula ₁₄ and having a molecular formula of _C16H22O9 and a molecular weight of _358.3 .

The synephrine in the present invention is an organic compound represented by Chemical Formula 15, having a molecular formula of C ₉ H ₁₃ NO ₂ and a molecular weight of 167.2.

The method for obtaining the compound in the present invention is not particularly limited, and it may be chemically synthesized by a method known in the art, or a commercially available substance may be used.

The compounds of the invention may exist in unsolvated as well as solvated forms. The compounds of the invention may exist in crystalline or amorphous forms, and all these physical forms are included in the invention.

One aspect of the present invention provides a quasi-drug composition for preventing or improving oral diseases, comprising the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

More specifically, the present invention provides dental caries, periodontal disease (periodontitis or gingivitis), toothache, hyperesthesia and halitosis, which contain the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. Provided is at least one quasi-drug composition for preventing or improving oral diseases selected from the group consisting of:

The "natural compound" is as described above.

The term "oral disease" in the present invention refers to various diseases that occur in the oral cavity, and the oral cavity refers to the space in the mouth that is connected to the pharynx from the anterior lip to the posterior isthmus. . The oral disease in the present invention is a concept that includes all diseases occurring in the oral cavity regardless of the disease, and examples of the oral disease include caries, periodontal disease (periodontitis or gingivitis), Examples include, but are not limited to, toothache, hypersensitivity, bad breath, and the like.

The term "dental cavities" as used in the present invention is an infectious disease caused by bacteria living on tooth surfaces, and is also called tooth decay. Specifically, enamel or enamel is a translucent milky-white hard substance that covers the upper surface of teeth and protects dentin. is produced, which damages the enamel of the tooth and causes caries. The main cause of dental caries is dental plaque, which is a film of bacteria formed on the surface of teeth. Oral microorganisms such as Streptococcus sobrinus and Streptococcus mutans, which are types of Morphoidococcus, adhere to form a biofilm, resulting in dental plaque. Produced and further thickened by Fusobacterium. The caries-causing bacteria in the present invention include all caries-causing bacteria regardless of their types, specifically Streptococcus mutans, Streptococcus sanguinis, and Streptococcus. - At least one bacterium selected from the group consisting of Streptococcus sobrinus, Streptococcus ratti, Streptococcus criceti, Streptococcus anginosus and lactic acid bacteria, more specifically is Streptococcus mutans.

The Streptococcus mutans is a type of streptococcus and is a gram-positive bacterium, and is also called a cariogenic bacterium. The Streptococcus mutans proliferates only on the surface of teeth, but milk teeth are not completed until around 30 months after birth. Therefore, until this stage, it is difficult to propagate Streptococcus mutans, as it was after infancy. If Streptococcus mutans does not infect the adult's mouth during childhood and other oral bacteria colonize the mouth, it is unlikely that Streptococcus mutans will newly invade the already balanced oral ecosystem. It is difficult, and after infancy, the probability of developing tooth decay is greatly reduced for the rest of one's life. If you have already been infected with the causative bacteria from the mouth of an adult, frequent tooth brushing and keeping your mouth clean can help prevent tooth decay. However, once Streptococcus mutans colonizes the oral cavity, eradication of Streptococcus mutans is impossible.

In one embodiment of the present invention, a medium smeared with Streptococcus mutans was inoculated with a disc containing the natural compound of the present invention, and then the size of the growth inhibition circle was measured. The diameter of the circle of inhibition is 10.0 mm or more, and the composition containing the natural compound is useful for caries prevention or amelioration because it exhibits excellent antibacterial activity against Streptococcus mutans. was confirmed (Table 2).

The term "periodontal disease" as used in the present invention refers to a disease in which inflammation occurs in the gingiva, periodontal ligament, and bone tissue that support the teeth. gingivitis) and periodontitis. Gingivitis is a periodontal disease that is relatively mild and recovers quickly and is confined to the gums, that is, soft tissues. Periodontitis is when the inflammation progresses to the gums and around the alveolar bone. There is a V-shaped gap between the gingiva (gums) and the teeth, and when oral pathogens attack the lower side of the gum line in the sulcus, lipopolysaccharide (LPS), which is an inflammatory stimulus, is released. The release creates an inflammation that causes the gums to swell and bleed, and damages the periodontal ligaments and adjacent tissues. As periodontitis progresses, it damages the periodontal ligament and alveolar bone, eventually leading to tooth loss. Nutrient deficiencies such as protein and vitamins, hormonal disturbances due to pregnancy and diabetes, smoking, acquired immunodeficiency syndrome (AIDS), etc. may exacerbate the disease. Other causes of periodontal disease include dental plaque and tartar. In the present invention, periodontal disease-causing bacteria include all causative bacteria that cause periodontal disease regardless of their types, specifically Actinobacillus actinomycetemcomitans, Porphyro At least one fungus selected from the group consisting of Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Fusobacterium nucleatum, more specifically is Porphyromonas gingivalis.

The Porphyromonas gingivalis is a gram-negative, anaerobic bacterium that is a kind of bacteria related to Bacteroides. Said Porphyromonas gingivalis is found in the oral cavity where periodontal disease occurs, as well as in the upper gastrointestinal tract, respiratory tract and colon. In patients with chronic periodontal disease, collagen is degraded by the bacterial collagenase enzyme. The bacteria can invade gingival fibroblasts and survive even under high concentrations of antibiotics. In addition, the bacteria can invade gingival epithelial cells and survive for a long period of time.

In one embodiment of the present invention, a medium smeared with Porphyromonas gingivalis was inoculated with a disk containing the natural compound of the present invention, and then the size of the growth inhibition circle was measured. The diameter of the growth-inhibitory circle was 10.0 mm or more, and the composition showed excellent antibacterial activity against Porphyromonas gingivalis. Therefore, the composition containing the compound is useful for preventing or improving periodontal disease. It was confirmed that there is (Table 2).

In addition, in one example of the present invention, as a result of conducting a clinical experiment by selecting experimental subjects with gingival inflammation, the experimental group using the experimental group toothpaste containing the above compound had an excellent effect of suppressing gingival inflammation, and the effect of suppressing gingival inflammation was excellent for 6 months. It was confirmed that the composition containing the natural compound is useful for the prevention or improvement of periodontal diseases including gingivitis ( Table 4).

The term "toothache" as used in the present invention means pain in the tooth when eating sweet food, very cold food, very hot food, etc. In general, not only pain in the tooth itself but also pain in the tooth It also includes pain in the periodontal tissue that holds the tooth to the jawbone. It usually causes pain when chewing, swollen gums, and foul-smelling discharge. Toothache presents somewhat different pain depending on the causative disease. Specifically, in the case of dental caries, there is no pain in the early stages, but as it progresses and reaches the nerve inside the tooth, pain appears. is induced and the tooth is crushed or cracked, when touching cold food or chewing hard, the tooth spreads and stimulates the nerve, causing pain. In the case of pulpitis, pain is felt when cold food is touched in the early stages, and when it progresses, pain is felt when hot food is touched. Loss of response and pain due to inflammation of the root apex (tip of the root) of the tooth.

In one example of the present invention, as a result of confirming the inhibitory effect of PGE2, which is known as a marker of pain and inflammation, it was confirmed that the experimental group containing the natural compound of the present invention exhibits the effect of inhibiting PGE2 in a concentration-dependent manner. (Table 5).

"Hypersensitivity" in the present invention means hypersensitive dentine, and hypersensitivity symptom means dentine hyperesthesia. Hypersensitivity symptoms are tooth stains that are felt sensitively when the exposed dentin part of the teeth comes into contact with cold air or irritating food, and 60 to 98% of adults with periodontal disease have symptoms. appear. Hypersensitivity symptoms appear due to incorrect tooth brushing habits, excessive bite force, teeth digging into the gums due to acid dissolution, poor oral hygiene, periodontal treatment, restorative treatment, and tooth dissolution due to acidification. The underlying cause of hyperesthesia symptoms is that many tubules in the dentin of the tooth are exposed to the outside. However, it reacts more sensitively than usual and causes pain. Symptoms of hypersensitivity range from mild symptoms to severe and persistent pain, but because teeth do not regenerate, taking pain relievers and anti-inflammatory agents is not a fundamental solution to tooth stains. Hypersensitivity symptoms may appear in general over the entire tooth, or they may appear in specific sites such as the upper jaw, lower jaw, right side, or left side. Although the most frequently affected sites differ depending on the cause, they are mainly canines and premolars, and the most painful site is the cervical region, which is the interface between gums and teeth in 90% or more.

In one example of the present invention, as a result of conducting a clinical experiment by selecting an experimental subject with hypersensitive dentin, the experimental group using the experimental group toothpaste containing the compound of the present invention showed an inhibitory effect on hypersensitivity symptoms. It was confirmed that the composition containing the natural compound is excellent and useful for preventing or improving hypersensitivity (Table 7).

The term "halitosis" as used in the present invention means an odor originating from the oral cavity and adjacent organs, and 85-90% of halitosis originates from the oral cavity, particularly from the back of the tongue. The main components of bad breath are volatile sulfur compounds, and 90% of the total amount of volatile sulfur compounds is hydrogen sulfide produced from cysteine, methyl mercaptan produced from methionine and dimethyl sulfide. It is a sulfide (dimethyl sulfide). These components are mainly produced by protein enzymes secreted by anaerobic bacteria, and their most important habitat is the back of the tongue. This area is poorly cleaned by saliva and has many small depressions, making it a habitat for bacteria. The most important cause of halitosis is the production of volatile sulfur compounds by anaerobic bacteria, but oral diseases such as dental caries, periodontitis, and xerostomia also cause halitosis. Various anaerobic bacteria are involved in the generation of halitosis, and the causative bacteria of halitosis include, for example, Porphyromonas gingivalis, which secretes a large amount of various types of enzymes. It is not limited.

In one example of the present invention, as a result of conducting a clinical trial on experimental subjects without dental caries, the experimental group using the experimental group toothpaste containing the natural compound of the present invention showed excellent bad breath removal effect, and the compound It was confirmed that the composition containing is useful for preventing or improving halitosis (Table 8).

The quasi-drug composition of the present invention may contain an oral quasi-drug. Ingredients contained in the quasi-drug composition of the present invention may include, in addition to the active ingredients described above, ingredients commonly used in oral quasi-drug compositions, such as abrasives, wetting agents, and binding agents. agents, foaming agents, sweeteners, preservatives, active ingredients, flavoring agents, dyes, solvents, brighteners, solubilizers or pH adjusters.

The oral quasi-drug composition of the present invention may be produced in any dosage form commonly produced in the art, such as toothpaste, mouthwash, mouthwash, gum, candies, oral spray, It may have dosage forms such as, but not limited to, oral ointments, oral varnishes, mouthwashes, gum massage creams, and the like.

As an example, when the oral quasi-drug composition of the present invention is in the form of toothpaste, wetting agents, abrasives, binders, foaming agents, flavoring agents, sweetening agents, coloring agents, preservatives, and medicinal ingredients are used. , solvents, pH adjusters, and the like.

The humectant is used to make the powder in the dentifrice into a paste and to prevent the dentifrice from solidifying in the air. It is used alone or in combination of two or more in an amount of 1 to 60% by weight, specifically 10 to 50% by weight, of the total weight of the composition.

The foaming agent diffuses the dentifrice into the oral cavity to improve the cleaning effect, and acts as a surfactant to cleanse the oral cavity, and includes sodium lauryl sulfate, sodium lauryl sarcosinate, and sodium alkyl sulfosuccinate. , Surfactants such as sucrose fatty acid esters alone or in combination of two or more so that the total weight of the composition is 0.5 to 10% by weight, specifically 0.5 to 5% by weight. use.

The binder prevents separation between the powder and the liquid component in the dentifrice, and is composed of cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylcellulose, sodium alginate, carrageenan, xanthan gum, etc. alone or in combination. The above are mixed and used in an amount of 0.1 to 5% by weight, specifically 0.3 to 2% by weight, of the total weight of the composition.

The abrasive removes deposits _on the surface of the teeth without damaging the surface of the teeth and allows the original _luster of the teeth to appear. _4.2H.sub.2O ), silicic anhydride _{( SiO.sub.2.2H.sub.2O} ), aluminum hydroxide (Al(OH) _.sub.3 ), potassium pyrophosphate, magnesium carbonate, etc., either alone or in combination of _two or more to form a composition 1 to 60% by weight, specifically 10 to 50% by weight of the total weight.

The flavoring agent is for adding a refreshing feeling and fragrance to the toothpaste and improving the feeling of use. It is used in an amount of 1 to 60% by weight, specifically 0.01 to 5% by weight.

The sweetening agent removes the unpleasant taste of the raw material of the dentifrice and improves the cooling sensation, and is composed of saccharic acid, aspartame, xylitol, glycyrrhizic acid, etc. alone or in combination of two or more. It is used in an amount of 1 to 60% by weight, specifically 0.01 to 5% by weight, of the total weight of the product.

The medicinal ingredients are for caries prevention, periodontal disease prevention, toothache prevention, hypersensitivity prevention, bad breath elimination, etc., and include fluoride, zinc chloride, chlorhexidine, aminocaproic acid, tranexamic acid, cetylpyridinium chloride, Pyridoxine chloride, triclosan, tocopherol acetate, sodium monofluorophosphate and the like are used alone or in combination of two or more. In the present invention, said compound is used as an additional medicinal ingredient.

The oral quasi-drug composition of the present invention can be used alone or in combination, and can also be used in combination with other oral quasi-drug compositions other than the present invention.

Another aspect of the present invention provides a pharmaceutical composition comprising the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. More specifically, the present invention provides at least one toothpaste selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, hypersensitivity and halitosis, which contains the natural compound as an active ingredient. Provided are pharmaceutical compositions for the prevention or treatment of two oral diseases. The natural compounds, oral diseases, dental caries, periodontal diseases, toothache, hypersensitivity and halitosis are as described above.

The pharmaceutical composition of the present invention can be prepared as tablets, pills, powders, granules, capsules, suspensions, liquids for internal use, emulsions, syrups and aerosols by conventional methods for preventing and treating oral diseases. It can be formulated in the form of pharmaceutical agents, sterile injectable solutions, and the like.

Oral solid dosage forms include tablets, pills, powders, granules, capsules, etc., and these solid dosage forms contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, and the like. It may be prepared by mixing. Besides ordinary excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, internal solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used diluents, various excipients such as wetting agents, Sweeteners, flavoring agents, preservatives and the like may be used.

Parenteral formulations include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories and the like. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

Additionally, the pharmaceutical composition of the present invention may further comprise a carrier, excipient or diluent. Carriers, excipients or diluents include lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, hydroxypropyl. Mineral oils such as methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and silicon dioxide are used.

The specific dosage of the pharmaceutical composition according to the present invention depends on factors such as formulation method, patient condition, body weight, sex, age, degree of disease, form of drug, administration route and period, excretion rate, reaction sensitivity, etc. A person skilled in the art can make various selections depending on the situation, and the dosage and frequency are not intended to limit the present invention in any aspect.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, domestic animals and humans by various routes. Although any method of administration is possible, it can be administered, for example, by oral, intravenous, intramuscular or subcutaneous injection.

Yet another aspect of the present invention provides a food composition comprising the natural compound or its food-acceptable salt as an active ingredient. Further, specifically, the present invention provides at least one selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, hypersensitivity and halitosis, which contains the compound as an active ingredient. Provided is a food composition for preventing or improving oral diseases. The natural compounds, oral diseases, dental caries, periodontal diseases, toothache, hypersensitivity and halitosis are as described above. The food composition may be used in the form of a functional food, but is not limited thereto.

The natural compound or food-acceptable salt thereof contained in the food composition of the present invention may be contained in the form of an animal or plant containing the compound, an extract thereof, a fraction thereof, or a processed product thereof. . In addition, the composition may contain a food supplementary food additive in addition to the active ingredient.

"Food supplementary additive" in the present invention means a component that is supplementarily added to food, is added when producing functional foods of each dosage form, and can be appropriately selected by those skilled in the art. can be used Examples of food supplement additives include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, coloring agents and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloids, thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages, etc.; The type is not limited.

The food composition of the present invention may contain functional foods. "Functional food" in the present invention means food manufactured and processed into forms such as tablets, capsules, powders, granules, liquids, and pills using raw materials and ingredients that have functionality useful for the human body. means Here, "functionality" means regulating nutrients to the structure and function of the human body or providing beneficial effects for health applications, such as physiological effects. The functional food of the present invention can be produced by a method commonly used in the technical field, and can be produced by adding raw materials and components that are commonly added in the technical field. Also, the dosage form of the functional food is not limited as long as it is a dosage form recognized as a functional food. The food composition of the present invention can be prepared in various dosage forms, and unlike general drugs, it has the advantage that it does not have side effects that may occur during long-term administration of drugs because it is made from food. Because of its excellent portability, the functional food of the present invention can be ingested as an adjuvant for preventing or improving oral diseases.

The form in which the functional food of the present invention is used is not limited, and includes all foods in the usual sense, and may be mixed with terms known in the art such as health functional food. In addition, the functional food of the present invention can be produced by mixing other suitable supplementary ingredients and known additives that can be contained in the food according to the selection of those skilled in the art. Examples of foods that can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products such as ice cream, various soups, and refreshing beverages. Drinking water, tea, drinks, alcoholic beverages, vitamin complexes, etc., can be mentioned, and can be produced by adding the compounds of the present invention to juices, teas, jellies, juices, etc. prepared as main ingredients. Also included are foods used as animal feed.

Hereinafter, the configuration and effects of the present invention will be described in more detail with reference to Examples and Experimental Examples. These Examples and Experimental Examples are merely to illustrate the present invention, and the present invention is not limited to these Examples and Experimental Examples.

Experimental Example 1 Antibacterial Effect on Causative Bacteria of Caries and Periodontitis An antibacterial activity experiment was conducted to confirm the preventive or therapeutic effect of the compounds of formulas 1 to 15 on caries and periodontitis. In order to confirm the effect of suppressing the growth of oral pathogens, Streptococcus mutans, a representative bacterium that induces dental caries, and Porphyromonas gingivalis, a representative bacterium that induces periodontal disease, were tested. ) was used to perform an antibacterial activity test by the paper disc test method.

The activity of each of the oral pathogens was increased under the optimum culture conditions shown in Table 1, and then cultured in the optimum medium for each bacterium for about 4 to 6 hours. 0.5 (1.5×10 ⁸ ), and 0.1 ml of each oral pathogen was spread evenly on the plate medium. Then, each of the compounds of Formulas 1 to 15 was inoculated on a sterilized paper disc (Whatman no.5 paper, 8 mm diameter) at a concentration of 10 mg/disc, and dried for 1 hour. Next, each oral pathogen was cultured at the optimum temperature for 24 to 48 hours, and then the size (diameter mm) of the growth inhibition circle was measured. Table 2 shows the results.

As can be seen from Table 2, compared with the untreated group, the group treated with the compounds of formulas 1 to 15 had a growth inhibition circle diameter of 9.5 mm or more against the two oral pathogens, and Streptococcus mutans and showed excellent antibacterial activity against Porphyromonas gingivalis. Therefore, it was found that the compounds of formulas 1 to 15 are useful for preventing or treating dental caries or periodontal disease.

Experimental Example 2: Effect of Inhibiting the Development of Gingivitis In order to confirm the preventive or therapeutic effect of the compounds of formulas 1 to 15 on gingivitis, a group of experimental subjects was selected and a clinical experiment was conducted.

First, a control was performed using sodium carboxymethylcellulose, sodium lauryl sulfate, glycerin, colloidal silicon dioxide, silicas, sodium cocoyl isethionate, dodicin, sweeteners, flavoring agents, coloring agents, etc., which are commonly used in the manufacture of toothpaste. A group toothpaste was prepared, and an experimental group toothpaste was prepared by adding 0.01% by weight of any compound of formulas 1 to 15 to the control group toothpaste.

In order to select subjects for the experiment, 30 males and 30 males and 30 females were selected every 10 years from 30 years old to 50 years old. A group of 120 experimental subjects was selected and divided into 60 subjects each, and a clinical experiment on the therapeutic effect of gingival inflammation was conducted as follows.

Specifically, the experimental subject group was divided into a control group and an experimental group, the control group was educated to use the control group toothpaste 3 times a day 2 hours after eating, and the experimental group was educated to use the experimental group. They were educated to use toothpaste three times a day at the same time as the control group. After that, the mouth was cleaned and the initial gingivitis index was scored, and the control group used the control group toothpaste, and the experimental group used the experimental group toothpaste, after 1 week, 1 month, 3 months and 6 months. A post-oral examination was performed to examine the gingivitis index. The method of measuring the gingivitis index is to insert a periodontal probe into the gingival sulcus and probe along the periphery of each tooth without applying force, and measure the state of bleeding after 30 seconds. , were scored according to the criteria shown in Table 3. Table 4 shows the results.

As can be seen from Table 4, compared with the control group, the experimental group using toothpaste containing any of the compounds of formulas 1 to 15 maintained a normal bleeding state even after 6 months, and gingival inflammation The inhibitory effect persisted. Therefore, it was found that the compounds of formulas 1 to 15 are useful for preventing or treating gingivitis.

Experimental Example 3: Inhibitory Effect of PGE2, a Marker of Pain and Inflammation In order to confirm the preventive or therapeutic effect of the compounds of Formulas 1 to 15 on toothache, the inhibitory effect of PGE2, a marker of pain and inflammation, was confirmed.

First, macrophages were inoculated in a DMEM medium containing 10% FBS at a concentration of 1.5×10 ⁵ cells/ml and cultured in a 24 well plate at 37° C. and 5% CO ₂ for 24 hours. Next, it is treated with 1 μg/ml of LPS, which is an inflammation-inducing stimulus, and compounds of chemical formulas 1 to 15 at various concentrations, and cultured for 24 hours. Compounds 1-15 were analyzed for their ability to inhibit PGE2 at each concentration (Table 5).

As can be seen from Table 5, when compared with the group treated with LPS alone, all compounds of formulas 1 to 15 were confirmed to exert a PGE2 inhibitory effect in a concentration-dependent manner, exhibiting excellent prophylactic and therapeutic effects on toothache. was confirmed.

Experimental Example 4 Inhibitory Effect of Hypersensitivity In order to confirm the preventive or therapeutic effect of the compounds of formulas 1 to 15 on hypersensitivity, a clinical experiment was conducted by selecting experimental subjects. The control group toothpaste and experimental group toothpaste used in the clinical experiment were prepared in the same manner as the toothpaste of Experimental Example 2, respectively.

The experimental subjects were 40 volunteers with hypersensitive dentine who consented to participate in the experiment. There were 80 teeth in total for the experiment. In addition, 20 males and 20 females were among the test subjects, and their ages ranged from 20 to 50 years old. The experimental subjects were blinded to the contents of the toothpaste and the total experimental period was 2 weeks.

The experiment was conducted by adding a temperature stimulus and measuring the reaction of the experiment subject. Prior to conducting the experiment, the sensitive site of the hypersensitive dentin of each test subject was checked in advance, and cold water of about 5°C was dripped on the site where the teeth were stinging with a dropper, and the score was scored according to the criteria shown in Table 6. After that, the control group used the control group toothpaste, and the experimental group used the experimental group toothpaste 3 times a day for 2 weeks. For statistical processing, the stimulation scores before and two weeks after the experiment were tested by a paired student-t test. Table 7 shows the reaction scores after 2 weeks to the temperature stimulation.

As can be seen from Table 7, the hypersensitivity phenomenon was suppressed after 2 weeks in the experimental group using the toothpaste containing each compound of formulas 1 to 15, compared with the control group. Therefore, it was found that the compounds of formulas 1 to 15 are useful for preventing or treating hypersensitivity.

Experimental Example 5: Effect of Eliminating Halitosis In order to confirm the preventive or therapeutic effect of the compounds of Formulas 1 to 15 on halitosis, a clinical experiment was conducted by selecting experimental subjects. The control group toothpaste and experimental group toothpaste used in the clinical experiment were prepared in the same manner as the toothpaste of Experimental Example 2, respectively.

50 males and females without dental caries were selected as experimental subjects, and a cross-over test was conducted using the control group toothpaste and the experimental group toothpaste. Commercially available garlic powder was dispersed in water and allowed to stand for 24 hours, then diluted to a Halimeter reading of 700 ppb or more, and the diluted solution was used as a halitosis inducer. The test subjects were asked to gargle with 15 ml of diluted garlic powder for 30 seconds, and after 1 minute, the degree of bad breath was measured with a halimator. They were allowed to use it to brush their teeth for 30 seconds to 1 minute. Halitometer was used to measure the degree of bad breath after 1 minute, 5 minutes, and 30 minutes after brushing the teeth, and it was determined whether the suppression of bad breath was maintained. Table 8 shows the results.

As can be seen from Table 8, compared with the control group, the experimental group using the toothpaste containing each compound of formulas 1 to 15 removed about 95% of bad breath 1 minute after brushing, and 30 minutes after brushing. In some cases, the bad breath removal rate was 80% or more, showing a far superior breath removal effect. Therefore, it was found that the compounds of formulas 1 to 15 are useful for preventing or treating halitosis.

Claims (14)

A quasi-drug composition for preventing or improving oral diseases, comprising albiflorin or a pharmaceutically acceptable salt thereof as an active ingredient. The quasi-drug composition according to claim 1, wherein the oral disease is dental caries. The quasi-drug composition according to claim 2, wherein the dental caries is caused by Streptococcus mutans. The quasi-drug composition according to claim 1, wherein the oral disease is periodontal disease. The quasi-drug composition according to claim 4, wherein the periodontal disease is periodontitis or gingivitis. The quasi-drug composition according to claim 4, wherein the periodontal disease is caused by Porphyromonas gingivalis. The quasi-drug composition according to claim 1, wherein the oral disease is toothache. The quasi-drug composition according to claim 1, wherein the oral disease is hypersensitivity. The quasi-drug composition according to claim 1, wherein the oral disease is halitosis. The quasi-drug composition according to claim 1, wherein the quasi-drug is for oral cavity use. The dosage form of the quasi-drug composition is selected from the group consisting of toothpaste, mouthwash, mouthwash, gum, candy, oral spray, oral ointment, oral varnish, mouthwash and gum massage cream. The quasi-drug composition according to claim 10, which is at least one dosage form to be administered. A pharmaceutical composition for preventing or treating oral diseases, comprising albiflorin or a pharmaceutically acceptable salt thereof as an active ingredient. A food composition for preventing or improving oral diseases, containing albiflorin or a food-acceptable salt thereof as an active ingredient. An oral composition comprising Albiflorin or an acceptable salt thereof as an active ingredient.