KR20210002760A - Composition for prevention or treatment or oral disease - Google Patents

Abstract

The present invention relates to a composition for preventing or treating oral diseases comprising a natural compound, and more particularly, to a quasi-drug composition having an effect of preventing or improving dental caries, periodontal disease, toothache, aching and bad breath. The composition of the present invention has excellent antibacterial activity against bacteria that cause dental caries and periodontal disease, inhibits PGE2, a marker of pain and inflammation, in a concentration-dependent manner, inhibits gingivitis formation, and suppresses symptoms and removes bad breath. It 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, aching and bad breath. In addition, the composition of the present invention can be used as a pharmaceutical composition and a food composition.

Description

Composition for prevention or treatment or oral disease}

The present invention relates to a composition for preventing or treating oral diseases comprising a natural compound as an active ingredient, and more particularly, to a quasi-drug composition having an effect of preventing or improving dental caries, periodontal disease, toothache, aches and bad breath. will be. In addition, the present invention relates to pharmaceutical compositions, food compositions, and oral compositions containing natural compounds as an active ingredient.

Healthy teeth are an important factor in determining the quality of life to the extent that it is called one of the five blessings. Among oral diseases, dental cavities (caries) and periodontal disease (Pungchi) are highly incidence diseases worldwide, and various clinical symptoms such as pain, masticatory dysfunction, destruction of periodontal tissue, bad breath, and aches and pains. It is known as the main factor that causes tooth loss and tooth loss, and the cause of oral disease is increasing due to changes in diet.

It is known that approximately 600 to 800 or more kinds of microorganisms exist in the human oral cavity, and these microorganisms are controlled by enzymes such as lysozyme secreted by saliva. However, the oral environment, which is rich in nutrients and moisture, is a good condition for the growth of microorganisms, and the tongue and dental plaque provide excellent habitat for microorganisms. Some of these microorganisms are opportunistic pathogenic bacteria and cause diseases such as dental caries, periodontal disease, and aching (denatin hypersensitivity) and bad breath.

There are antibacterial agents as a method of inhibiting the proliferation of oral pathogens that inhabit dental caries, periodontal disease, bad breath and aching teeth while inhabiting the plaque, and various kinds of antibacterial agents including antibiotics having sterilization and bacteriostatic action against oral pathogens are used for caries, It has been developed as a treatment and suppression of periodontal disease, pulp and apical infection.

However, since antibiotics can cause systemic side effects on our body, the appearance of resistant bacteria in the oral cavity and superinfection, long-term use is difficult, and thus can only be used as a therapeutic agent. In addition, as antibacterial agents used in mouthwashes, there are Sangquinarine, Listerine, Peroxide, and Chlorhexidine, but the effect of saengquinarine on bacteria in the oral cavity is unclear. The treatment effect for periodontal disease is more unclear and the price is high. Listerine has a slight bacteriostatic effect as a main component of alcohol, but it has only a temporary effect in the oral cavity, and when used for a long period of time, it has a negative effect on the tissue. There are drawbacks that can appear. In addition, pyroxide, which has been recently added for whitening effect, is toxic to bacteria, but at the same time, it is toxic to human tissues, so there is a problem in safety, and sometimes bacteria resistant to pyroxide appear. In addition, chlorhexidine is known to be the best among the formulations known to date as a prevention and treatment for periodontal disease as well as inhibiting plaque formation, but it causes irritation to tissues, coloration and degeneration of tissues, and especially has strong irritating taste and severe odor side effects. In addition to the problems shown, there is a disadvantage that it cannot be used for a long period of time for treatment or especially for the purpose of prevention, such as it may cause apoptosis, and the use of pregnant women is restricted due to carcinogenicity.

In addition, a compound artificially synthesized through a chemical reaction may exhibit cytotoxicity or may cause side effects such as accumulation in the human body, and thus a study on the pharmacological activity of natural compounds with a low possibility of side effects in terms of safety is required.

The present inventors conducted a study to derive a natural material that is excellent in the prevention and improvement of oral diseases such as dental caries, periodontal disease, toothache, aching teeth, and bad breath without concern for the side effects as described above. As a result, natural compounds that are safe and can be used safely in the body have antimicrobial effects against bacteria that cause dental caries and periodontal disease, alleviate toothache through PGE2 inhibitory effects, inhibit gingivitis formation, suppress ache and remove bad breath. By finding out that it is represented, quasi-drug compositions, pharmaceutical compositions, food compositions, and oral compositions using them were completed.

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

Another object of the present invention is to provide a food composition for preventing or improving oral diseases comprising a natural compound or a food pharmaceutically acceptable salt thereof as an active ingredient.

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

The quasi-drug composition comprising the natural compound of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient is excellent in preventing or improving oral diseases. Specifically, the composition of the present invention has excellent antimicrobial activity against bacteria that cause dental caries and periodontal disease, inhibits PGE2, a marker of pain and inflammation, in a concentration-dependent manner, has an effect of inhibiting gingivitis formation, an effect of suppressing symptoms and removing bad breath. It is excellent and has high utilization as a quasi-drug composition for preventing or improving at least one oral disease selected from the group consisting of dental caries, periodontal disease, aching and bad breath. In addition, the composition containing the natural compound of the present invention can be used as a pharmaceutical composition and a food composition.

Best mode for carrying out the invention

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 in order to solve the above problems and achieve the object of the present invention.

As another aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating oral diseases comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

* As another aspect of the present invention, it provides a food composition for preventing or improving oral diseases comprising a natural compound or a food wise acceptable salt thereof as an active ingredient.

As another aspect of the present invention, it 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 comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

The'natural compound' refers to a substance that is directly made from organisms such as microorganisms, plants, animals, etc., and can be extracted, separated, or purified therefrom, and as specific examples of the natural compounds, Albiflorin, Astragal Astragaloside I, Brassinolide, Eleutheroside E, Geniopicrin, Gramine, Liensinine, Macroantoidin B ( Macranthoidin B), Neohesperidin dihydrochalcone, Obacunone, Oxysophocarpine, Sclareolide, Sophoricoside, Sweroside , Synephrine, and the like, but are not limited thereto.

In the present invention, the albiflorin is an organic compound represented by Chemical Formula 1 and having a molecular formula of C ₂₃ H ₂₈ O ₁₁ and a molecular weight of 408.4.

In the present invention, the astragaloside I 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.

In the present invention, the brassinolide 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.

In the present invention, the Eleutheroside E 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.

In the present invention, the genthiopicrin 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.

In the present invention, the gramine (Gramine) is an organic compound represented by the formula 6 and having a molecular formula of C ₁₁ H ₁₄ N ₂ , molecular weight 174.

In the present invention, the Liensinine is an organic compound represented by Chemical Formula 7 and having a molecular formula of C ₃₇ H ₄₂ N ₂ O ₆ and a molecular weight of 610.7.

In the present invention, the macranthoidin B 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.

In the present invention, the neohesperidin dihydrochalcone is an organic compound represented by Chemical Formula 9 and having a molecular formula of C ₂₈ H ₃₆ O ₁₅ and a molecular weight of 612.5.

In the present invention, the obacunone 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.

In the present invention, the oxysophocarpine is an organic compound represented by Chemical Formula 11 and having a molecular formula of C ₁₅ H ₂₂ N ₂ O ₂ and a molecular weight of 262.4.

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

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

In the present invention, the sweroside is an organic compound represented by Chemical Formula 14 and having a molecular formula of C ₁₆ H ₂₂ O ₉ and a molecular weight of 358.3.

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

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

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

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.

In addition, specifically, the present invention includes at least one oral cavity selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, ache, and bad breath containing the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. It can provide a quasi-drug composition for disease prevention or improvement.

The'natural compound' is as described above.

In the present invention, “oral disease” refers to various diseases occurring in the oral region, and the oral region refers to a space in the mouth that is connected to the pharynx from the front lip to the posterior oral cavity. In the present invention, if the oral disease is a disease occurring in the oral cavity, the concept includes all regardless of the condition, and non-limiting examples of the oral disease include dental caries, periodontal disease (periodontitis or gingivitis), toothache, ache, bad breath And the like.

In the present invention, "dental cavities" is an infectious disease caused by bacteria living on the tooth surface, and is also referred to as caries, and the hard tissue of the tooth is eroded to show a defect. Specifically, the milky, translucent and hard material that covers the surface of the tooth's head and protects the tooth dentin is called tooth enamel or enamel. It means that the enamel of the tooth is damaged, resulting in caries. The main cause of dental caries is dental plaque (plaque), which is a bacterial film formed on the surface of the tooth. Saliva forms a thin and sticky film on the tooth, on which Streptococcus sobrinus Oral microbes such as ( Streptococcus sobrinus ) bacteria and Streptococcus mutans attach to form a biofilm to form a dental plaque (plaque), which is thicker by Fusobacterium . Lose. Dental caries of the present invention if the organisms that cause dental caries but includes, regardless of their kinds, specifically Streptococcus mutans (Streptococcus mutans), Streptococcus Sangu yiniseu (Streptococcus sanguinis), Streptococcus small debris Taunus (Streptococcus sobrinus ), Streptococcus ratti , Streptococcus criceti , Streptococcus anginosus , and one or more selected from the group consisting of lactic acid bacteria, and more specifically, Streptococcus ratti May be mutans.

The Streptococcus mutans is a type of streptococcus, which is a gram-positive bacterium, and is also called a caries bacteria. The Streptococcus mutans proliferate only on the surface of the tooth, but the teeth are not completed until around 30 months of age. Therefore, it is difficult for Mutans to proliferate until this time, as after infancy. During infancy, if other oral bacteria are not infected from the mouths of adults and other oral bacteria settle in the mouth, it is difficult for the new mutans bacteria to enter the ecosystem within the oral cavity, which is already well-balanced. Becomes lower. If the causative agent is already transmitted through the mouth of adults, brushing your teeth frequently and keeping the mouth clean will help prevent tooth decay. However, once the mutans are located in the oral cavity, it is impossible to eradicate the mutans.

In one embodiment of the present invention, after inoculation of a disk containing the natural compound of the present invention on a medium coated with Streptococcus mutans, the size of the growth inhibition ring was measured. In the case of the experimental group containing the compound, growth inhibition It was confirmed that the ring diameter was 10.0 mm or more and exhibited quite excellent antimicrobial activity against Streptococcus mutans, so that the composition containing the natural compound can be used for preventing or improving dental caries (Table 2).

In the present invention, "periodontal disease" is a disease in which inflammation occurs in the gingival, periodontal ligaments and bone tissues supporting the teeth, and is commonly referred to as pungchi, depending on the severity of the disease, gingivitis and periodontitis. It is divided into. It is a relatively light and quick recovery form of periodontal disease. The form limited to the gums, that is, soft tissues, is called gingivitis, and the case where this inflammation progresses to the gums and around the gum bones is called periodontitis. There is a V-shaped gap between the gingiva (gum) and the tooth, and oral pathogens attack the lower part of the gingival line of this sulcus, releasing lipopolysaccharide (LPS), which is an inflammatory stimulus. Inflammation is generated, such as swelling of the gums and bleeding, which damages the periodontal ligaments and adjacent tissues. When periodontitis progresses, the periodontal ligament and even the alveolar bone are damaged, and the tooth is eventually lost. Malnutrition such as protein and vitamins, hormonal disorders such as pregnancy or diabetes, smoking, acquired immunodeficiency syndrome (AIDS), etc. can worsen the disease. In addition, other causes of periodontal disease include plaque and tartar. Periodontal disease of the present invention is included regardless of the type of bacteria causing periodontal disease, but specifically Actinobacillus actinomycetemcomitans ( Actinobacillus actinomycetemcomitans ), Porphyromonas gingivalis ( Porphyromonas gingivalis ), Tane Rella forsythia ( Tannerella forsythia ), Treponema denticola ( Treponema denticola ) and Fusobacterium nucleatum ( Fusobacterium nucleatum ) can be at least one homogeneous selected from the group consisting of, more specifically, forsythia forsythia . It could be a balis.

The Porphyromonas gingivalis is a gram-negative bacterium and an anaerobic bacterium as a kind of bacterioide-related bacteria. The Porphyromonas gingivalis is found in the oral cavity where periodontal disease has occurred, and is also found in the upper gastrointestinal tract, respiratory tract, and colon. In patients with chronic periodontal disease, collagen is decomposed by the bacteria's collagenase enzyme, and the bacteria can invade gingival fibroblasts and survive even under a considerable concentration of antibiotics. In addition, the bacteria can survive for a long time by invading the gingival epithelial cells.

In one embodiment of the present invention, after inoculation of a disk containing the natural compound of the present invention on a medium smeared with Popyromonas gingivalis, the size of the growth inhibition ring was measured, and in the case of the experimental group containing the compound, growth It was confirmed that the composition containing the compound can be used for preventing or improving periodontal disease because the low-lying ring diameter is 10.0 mm or more and exhibits a fairly excellent antibacterial activity against Popyromonas gingivalis (Table 2).

In addition, in an embodiment of the present invention, as a result of selecting a test subject having gingival inflammation and conducting a clinical experiment, in the case of the experimental group using the experimental group toothpaste containing the compound, the effect of inhibiting gingival inflammation is excellent and even after 6 months It was confirmed that the composition containing the natural compound can be used for preventing or improving periodontal diseases including gingivitis because the normal bleeding state is maintained and the gingivitis inhibitory effect is maintained (Table 4).

In the present invention, "toothache" refers to pain in the teeth when eating sweet food or very cold or hot food. In general, not only the pain of the tooth itself, but also of the periodontal tissue supporting the tooth Includes pain. It usually causes pain when chewing, swelling of the gums and discharge of an unpleasant smell. Toothache shows slightly different pain depending on the cause of the disease. Specifically, the pain caused by dental caries is initially painless, but gradually progresses to deeply rotten nerves in the teeth. Pain appears, and if there is an ambush, it is caused by inflammation of the tissue around the tooth. Pain is caused, and when the tooth is broken or cracked, when it comes into contact with cold food or is bitten strongly, the tooth cracks and irritates the nerves, causing pain. In the case of pulpitis, initially, you feel pain when cold food touches it, and if it is more advanced, you feel pain from hot food, and when inflammation progresses and the pulp tissue dies, there is no reaction to cold or hot things, and the apex (end of tooth root) The pain is caused by inflammation of the skin.

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

In the present invention, "syrini" refers to hypersensitive dentine teeth, and the "syrini" symptom refers to dentin hyperesthesia (dentine hyperesthesia). This symptom is sensitive when the dentin part of the exposed tooth comes into contact with cold air or irritating food, and it is a symptom in 60 to 98% of adults with periodontal disease. The symptoms of aching are when teeth are dent in the gum side due to incorrect brushing habits, excessive occlusal force, dissolution by acid, poor oral hygiene, after periodontal treatment, after restoration treatment, and when teeth are dissolved due to acidification. Can appear. Ache is the underlying cause of the symptom, and it appears as many tubules present in the dentin of the tooth are exposed to the outside.By exposure, all stimuli are transmitted to the pulp nerve as it is, reacting more sensitively to the same stimulus than usual, and can cause pain. have. The symptoms of ache can vary from mild to intense and persistent pain, and because of the nature of the tooth, it is not regenerated, so taking pain relievers or anti-inflammatory drugs is not a fundamental solution to the aching symptoms. The symptoms of aching may appear throughout the entire tooth, and may be limited to specific areas such as the upper or lower jaw, or the right or left. The most affected areas depend on the cause, but mainly canines and small molar areas, and the most severely painful areas are the cervical area, which is the boundary between the gums and teeth.

In one embodiment of the present invention, as a result of performing a clinical experiment by selecting an experiment subject with hypersensitivity teeth to dentin, in the case of the experimental group using the experimental group toothpaste containing the compound of the present invention, syrin has excellent symptom suppression effect. It was confirmed that the composition containing the natural compound can be used for prevention or improvement of syrin (Table 7).

In the present invention, "bad breath" is a smell originating from the oral cavity and adjacent organs, and 85 to 90% of bad breath originates from the oral cavity, and in particular, originates 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 made from cysteine and methyl mercaptan and dimethyl sulfide made from methionine. These components are mainly produced by protein enzymes secreted by anaerobic bacteria, and the back of the tongue is the most important habitat. This area is not well cleaned by saliva, and there are many small depressions, making it a place where bacteria continue to live. The generation of volatile sulfur compounds by anaerobic bacteria is the most important cause of bad breath, but it is also caused by oral diseases such as dental caries, periodontitis, and dry mouth. Many types of anaerobic bacteria are involved in generating bad breath, and a non-limiting example of a bacteria that causes bad breath may include Porphyromonas gingivalis , which secretes many types and large amounts of enzymes.

In one embodiment of the present invention, as a result of conducting a clinical experiment on an experimental subject without dental caries, in the case of the experimental group using the experimental group toothpaste containing the natural compound of the present invention, the effect of removing bad breath was excellent, and the compound was used. It was confirmed that the containing composition can be used for preventing or improving bad breath (Table 8).

The quasi-drug composition of the present invention may include a quasi-drug for oral cavity. Ingredients included in the quasi-drug composition of the present invention may include ingredients commonly used in oral quasi-drug compositions in addition to the above active ingredients as active ingredients, such as abrasives, wetting agents, binders, foaming agents, sweeteners, preservatives, medicinal ingredients, flavors. It may contain an agent, a colorant, a solvent, a whitening agent, a solubilizing agent, or a pH adjusting agent.

The oral quasi-drug composition of the present invention may be prepared in any formulation commonly prepared in the art, for example, toothpaste, mouthwash, mouthwash, gum, candy, mouth spray, oral ointment, oral varnish , Oral mouthwash and gum massage cream may have a formulation, but is not limited thereto.

As an example, when the oral quasi-drug composition of the present invention is a toothpaste formulation, it may include a wetting agent, an abrasive, a binder, a foaming agent, a flavoring agent, a sweetening agent, a coloring agent, a preservative, an active ingredient, a solvent, a pH adjusting agent, and the like.

The humectant is to make the powder of the toothpaste component into a paste and to prevent the toothpaste from hardening in the air.Glycerin, sorbitic solution, propylene glycol, polyethylene glycol, etc., alone or in combination of two or more, 1 ~ 60 weight of the total weight of the composition %, specifically, 10 to 50% by weight may be used.

The foaming agent increases the cleaning effect by diffusing the toothpaste into the oral cavity and acts as a surfactant to clean the oral cavity. Surfactants such as sodium lauryl sulfate, sodium lauryl sarcosinate, sodium alkyl sulfosuccinate, and sucrose fatty acid esters are used alone. Alternatively, two or more types may be mixed to use 0.5 to 10% by weight, specifically 0.5 to 5% by weight of the total weight of the composition.

The binder prevents the separation between the powder and the liquid component in the toothpaste. Cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, and hydroxypropylcellulose, and sodium alginate, carrageenan, xanthan gum, etc., are used alone or in combination of two or more. 0.1 to 5% by weight, specifically 0.3 to 2% by weight of the total weight of the composition may be used.

The abrasive removes adhesions on the tooth surface without damaging the tooth surface and makes the tooth's original gloss shine.Calcium carbonate (CaCO ₃ ), dicalcium phosphate (CaHPO ₄ , CaHPO ₄ 2H ₂ O), silicic anhydride (SiO ₂ 2H ₂ O), aluminum hydroxide (Al(OH) ₃ ), potassium pyrophosphate, magnesium carbonate, etc., alone or in combination of two or more, to add 1 to 60% by weight, specifically 10 to 50% by weight of the total weight of the composition. Can be used.

The flavoring agent is intended to enhance the feeling of use by imparting a refreshing feeling and odor to the toothpaste, and peppermint oil, spearmint oil, menthol, etc., alone or in combination of two or more, of 0.01 to 60% by weight, specifically 0.01 to 5% by weight can be used.

The sweetening agent is to remove unpleasant taste from the toothpaste raw material and improve the refreshing sensation.Saccharic acid, aspartame, xylitol, licorice, etc., alone or in combination of two or more, are 0.01 to 60% by weight of the total weight of the composition, specifically 0.01 to 5% by weight can be used.

The medicinal ingredients are for prevention of caries and periodontal disease, prevention of toothache, prevention of chills, and elimination of bad breath. Triclosan, tocopherol acetate, sodium monofluorophosphate, etc. may be used alone or in combination of two or more. In the present invention, the compound can be used as an additional medicinal ingredient.

The oral quasi-drug composition of the present invention may be used alone or in duplicate, or may be used in duplicate with other oral quasi-drug compositions other than the present invention.

As another aspect of the present invention, there is provided a pharmaceutical composition comprising the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. In addition, specifically, the present invention is a pharmaceutical composition for the prevention or treatment of at least one oral disease selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, ache and bad breath comprising the natural compound as an active ingredient Can provide. The natural compound, oral disease, dental caries, periodontal disease, toothache, aching and bad breath are as described above.

The pharmaceutical composition of the present invention is in the form of tablets, pills, powders, granules, capsules, suspensions, liquids, emulsions, syrups, aerosols, sterile injectable solutions, etc. according to conventional methods for preventing and treating oral diseases. Formulation is possible.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations are prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. Can be. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc may be used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, syrups, etc., and various excipients, such as humectants, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are commonly used simple diluents. Can be used.

Formulations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, suppositories, and the like. As the non-aqueous solvent and the suspension solvent, vegetable oils such as propylene glycol, polyethylene glycol, olive oil, and injectable esters such as ethyl oleate may be used.

In addition, the pharmaceutical composition of the present invention may further include a carrier, excipient or diluent. Carriers, excipients or diluents include lactose, textrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydroxy Mineral oils such as propyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, flophilhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and silicon dioxide can be used. have.

The specific dosage of the pharmaceutical composition according to the present invention depends on factors such as formulation method, patient's condition and weight, patient's sex, age, degree of disease, drug type, route and duration of administration, excretion rate, response sensitivity, etc. It can be selected in various ways by those skilled in the art, and the dosage and frequency do not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention can be administered to mammals such as mice, mice, livestock, and humans through various routes. All modes of administration can be expected and can be administered, for example by oral, intravenous, intramuscular or subcutaneous injection.

As yet another aspect of the present invention, the present invention provides a food composition comprising the natural compound or a food pharmaceutically acceptable salt thereof as an active ingredient. In addition, specifically, the present invention provides a food composition for preventing or improving at least one oral disease selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, aches and bad breath comprising the compound as an active ingredient can do. The natural compound, oral disease, dental caries, periodontal disease, toothache, aching and bad breath are as described above. The food composition may be used in the form of a health functional food, but is not limited thereto.

The natural compound or a food pharmaceutically acceptable salt thereof included in the food composition of the present invention may be included in the form of an animal or plant including the compound, an extract thereof, a fraction thereof, or a processed product thereof. In addition, the composition may contain food additives that are acceptable food additives in addition to the active ingredient.

In the present invention, the term "food supplementary additive" refers to a component that can be added auxiliary to food, and is added to the manufacture of health functional foods of each formulation, and can be appropriately selected and used by those skilled in the art. Examples of food additives include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavors and natural flavoring agents, coloring agents and fillers, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners. , pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, etc. are included, but the types of food additives of the present invention are not limited by the above examples.

The food composition of the present invention may contain 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 and pills using raw materials or ingredients having useful functions for the human body. Here, "functionality" refers to obtaining useful effects for health purposes such as controlling nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be prepared by a method commonly used in the art, and at the time of production, it can be prepared by adding raw materials and ingredients commonly added in the art. In addition, the formulation of the health functional food may be prepared without limitation as long as it is a formulation recognized as a health functional food. The food composition of the present invention can be prepared in various forms of formulation, and unlike general drugs, it has the advantage of not having side effects that may occur when taking the drug for a long time using food as a raw material, and is excellent in portability. Health functional foods can be consumed as supplements to prevent or improve oral diseases.

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

Mode for carrying out the invention

Hereinafter, the configuration and effects of the present invention will be described in more detail through examples and experimental examples. These Examples and Experimental Examples are for illustrative purposes only, and the scope of the present invention is not limited by these Examples and Experimental Examples.

Experimental Example 1: Antibacterial effect against bacteria that cause dental caries and periodontitis

Antimicrobial activity experiments were performed to confirm the preventive or therapeutic effect of the compounds of Formulas 1 to 15 on dental caries and periodontitis. To confirm the effect of inhibiting the growth of oral pathogens, the antibacterial activity was tested by using a paper disc test using Streptococcus mutans , a bacterium that causes dental caries, and Porphyromonas gingivalis , a bacterium that causes periodontal disease. Was carried out.

After increasing the activity of each of the oral pathogens in the optimal culture conditions shown in Table 1 below, incubation for 4 to 6 hours in the optimum culture medium of each bacteria was performed to adjust the turbidity of the culture medium to Macfarland turbidity No. Adjusted to be 0.5 (1.5 X 10 ⁸ ), 0.1ml of each oral pathogen was evenly spread on a plate medium. Thereafter, the compounds of Formulas 1 to 15 were inoculated into sterilized paper disks (Whatman no. 5 paper, 8 mm diameter) at a concentration of 10 mg/disc, respectively, and absorbed and dried for 1 hour. Then, after culturing at the optimum temperature of each oral pathogen for 24 to 48 hours, the size (diameter mm) of the growth inhibition ring was measured, and the results are shown in Table 2 below.

Strain Optimal condition Gram staining Strain name Temperature badge characteristics Gram (+) Streptococcus mutans 37 BHI Painless anaerobic Gram (-) Porphyromonas gingivalis 37 TSA Hemin Menadione Badge Anaerobic

Measurement result of antibacterial activity against oral pathogens of compounds of formulas 1 to 15 Growth inhibition ring diameter (mm) Streptococcus mutans Porphyromonas gingivalis No treatment -(Growth is not inhibited) -(Growth is not inhibited) Albiflorin 10.0 9.9 Astragalloside I 10.1 10.6 Brassinolide 10.1 10.1 Eleuteroside E 10.5 9.9 Genthiopicrin 11.3 11.0 Gramine 10.6 10.1 Reenginein 10.6 10.0 Macrontoidine B 10.5 10.2 Neohesperidine dihydrochalcone 10.5 10.2 Obakunon 11.8 12.0 Oxysophocarpine 10.3 10.8 Scraleolide 11.8 12.0 Sophoricoside 10.1 9.9 Swaroside 11.0 10.2 Synephrine 9.5 9.9

As shown in Table 2, when compared to the untreated group, the group treated with the compounds of Formulas 1 to 15 had a growth inhibition ring diameter of 9.5 mm or more for the two oral pathogens, and Streptococcus mutans and foreskin It showed very good antibacterial activity against Lomonas gingivalis. Accordingly, it was found that the compounds of Formulas 1 to 15 can be used to prevent or treat dental caries or periodontal disease. Experimental Example 2: Effect of inhibiting gingivitis formation

In order to confirm the effect of the compounds of Formulas 1 to 15 on preventing or treating gingivitis, a clinical experiment was performed by selecting the test subjects.

First, sodium carboxymethyl cellulose, sodium lauryl sulfate, glycerin, colloidal silicon dioxide, silicas, sodium sodium cocoyl isethionate, dodisin and sweeteners, fragrances, colorants, etc., which are generally used in the manufacture of toothpaste, are used. Thus, a control toothpaste was prepared, and an experimental group toothpaste was prepared by containing 0.01% by weight of one compound of the compounds of Formulas 1 to 15 in the control toothpaste.

In order to select the test subjects, precise oral examinations were performed for patients with gingivitis with even teeth and no defective teeth, 30 patients by gender at 10 years intervals from 30 to 50 years old by age, and then 120 subjects were examined. After screening, a clinical trial was conducted as follows for the treatment effect of gingivitis by dividing into 60 patients.

Specifically, the experimental target group was divided into a control group and an experimental group, and the control group was trained to use the prepared control toothpaste three times a day before going to sleep after 2 hours after eating, and the experimental group used the prepared experimental group toothpaste three times a day at the same time. Trained to do. Afterwards, dental scrubs were performed to score the initial gingivitis index, and the control group used the prepared control toothpaste, and the test group used the prepared test group toothpaste. After 1 week, 1 month, 3 months and 6 months, oral examination was conducted. The gingivitis index was examined. The method of measuring the gingivitis index is to insert a periodontal probe into the gingival fissure, burn the periphery of each tooth without applying force, and measure the bleeding state after 30 seconds. Scores were recorded accordingly, and the results are shown in Table 4.

Gingivitis Index Criteria score Contents 0 points No bleeding 1 point Normal bleeding 2 points Linear bleeding 3 points Interdental triangular bleeding 4 points Bleeding condition

Inhibitory effect of gingivitis 0 weeks 1 week 1 month 3 months 6 months Control 1.04 1.60 2.69 2.77 2.85 Albiflorin 1.05 1.08 1.09 1.11 1.12 Astragalloside I 1.05 1.06 1.09 1.12 1.16 Brassinolide 1.06 1.08 1.10 1.13 1.15 Eleuteroside E 1.05 1.08 1.09 1.12 1.14 Genthiopicrin 1.05 1.05 1.06 1.08 1.08 Gramine 1.04 1.07 1.08 1.10 1.12 Reenginein 1.05 1.04 1.08 1.11 1.14 Macrontoidine B 1.04 1.06 1.10 1.12 1.14 Neohesperidine dihydrochalcone 1.04 1.05 1.08 1.10 1.12 Obakunon 1.04 1.04 1.06 1.06 1.07 Oxysophocarpine 1.05 1.07 1.09 1.13 1.15 Scraleolide 1.06 1.06 1.07 1.08 1.09 Sophoricoside 1.06 1.08 1.09 1.11 1.14 Swaroside 1.05 1.08 1.09 1.12 1.14 Synephrine 1.04 1.05 1.08 1.10 1.11

As shown in Table 4, when compared to the control group, the experimental group using a toothpaste containing one of the compounds of Formulas 1 to 15 maintained a normal bleeding state even after 6 months, and the effect of inhibiting gingivitis continued. . Therefore, it was found that the compounds of Formulas 1 to 15 can be used for preventing or treating gingivitis. Experimental Example 3: Pain and inflammation marker PGE2 inhibitory effect

In order to confirm the effect of the compounds of Formulas 1 to 15 on preventing or treating toothache, the inhibitory effect of PGE2 known as a pain and inflammation marker was confirmed.

First, macrophages were inoculated at a concentration of 1.5 X 10 ⁵ cells/ml in DMEM medium containing 10% FBS, and cultured for 24 hours in a 24 well plate at 37°C and 5% CO ₂ . Then, 1 μg/ml of LPS, which is an inflammation inducing stimulus, and each of the compounds of Formulas 1 to 15 were treated by concentration and cultured for an additional 24 hours. Then, PGE2 ELISA assay kit (Thermo SCIENTIFIC) was purchased and the above formula PGE2 inhibitory ability according to the concentration of compounds 1 to 15 was analyzed (Table 5).

Confirmation of PGE2 inhibitory effect (PGE2 relative ratio (%)) (-)/(-) LPS/(-) Control 3 100 LPS/2ppm LPS/20ppm Albiflorin 50 28 Astragalloside I 79 58 Brassinolide 51 23 Eleuteroside E 56 37 Genthiopicrin 26 9 Gramine 72 42 Reenginein 61 34 Macrontoidine B 60 37 Neohesperidine dihydrochalcone 26 9 Obakunon 37 16 Oxysophocarpine 79 50 Scraleolide 42 17 Sophoricoside 70 46 Swaroside 59 38 Synephrine 80 59

As shown in Table 5, when compared with the group treated with only LPS, it was confirmed that all of the compounds of Formulas 1 to 15 showed a concentration-dependent PGE2 inhibitory effect, and thus it was confirmed that the prevention and treatment effect of toothache is excellent. Experimental Example 4: Inhibitory effect of syringin

In order to confirm the preventive or therapeutic effect of the compounds of Formulas 1 to 15, the test subjects were selected to perform a clinical experiment, and the control toothpaste and the experimental group toothpaste used in the clinical test were the same as the toothpaste of Experimental Example 2. Each was prepared.

The test subjects were people with hypersensitivity teeth, 40 volunteers who agreed to participate in this experiment, and a total of 80 teeth were tested. In addition, among the test subjects, there were 20 males and 20 females, and the age ranged from 20 to 50 years old. The test subjects were not allowed to know the contents of the toothpaste, and the total test period was 2 weeks.

The experiment was carried out by measuring the reaction of the test subject after applying temperature stimulation. Before conducting the experiment, check the sensitive area of each subject's dentin hypersensitivity tooth in advance, and drop cold water of about 5℃ with a dropper on the aching area of the tooth, and score according to the criteria shown in Table 6 below. The control toothpaste was used in the experimental group three times a day for two weeks, and after two weeks, cold water of about 5° C. was dropped with a dropper to score. For statistical processing, the stimulation scores before and after 2 weeks of the experiment were tested by a paired Student-t test, and the response scores after 2 weeks to the temperature stimulation are shown in Table 7 below.

Based on the subject's rating after stimulation score Contents 0 points There is no discomfort. 1 point Slightly uncomfortable or cold. 2 points It's very cold. 3 points pain.

The degree of suppression of the ache 0 weeks 2 weeks Control 2.15±0.22 2.13±0.20 p>0.05 Albiflorin 2.14±0.18 1.87±0.23 *p<0.05 Astragalloside I 2.15±0.15 1.90±0.11 *p<0.05 Brassinolide 2.14±0.07 1.83±0.21 *p<0.05 Eleuteroside E 2.13±0.15 1.87±0.23 *p<0.05 Genthiopicrin 2.14±0.17 1.73±0.11 *p<0.05 Gramine 2.13±0.21 1.90±0.10 *p<0.05 Reenginein 2.14±0.13 1.89±0.17 *p<0.05 Macrontoidine B 2.14±0.16 1.88±0.20 *p<0.05 Neohesperidine dihydrochalcone 2.13±0.08 1.85±0.12 *p<0.05 Obakunon 2.14±0.18 1.73±0.10 *p<0.05 Oxysophocarpine 2.13±0.14 1.89±0.02 *p<0.05 Scraleolide 2.15±0.10 1.78±0.09 *p<0.05 Sophoricoside 2.13±0.14 1.84±0.20 *p<0.05 Swaroside 2.14±0.10 1.88±0.01 *p<0.05 Synephrine 2.14±0.07 1.86±0.18 *p<0.05

※ p>0.05: 95% confidence, no statistically significant difference. *p<0.05: 95% confidence, there is a statistically significant difference As shown in Table 7 above, when compared to the control group, the experimental group using the toothpaste containing each of the compounds of Formulas 1 to 15 has elapsed 2 weeks After aching symptoms were suppressed. Therefore, it was found that the compounds of Formulas 1 to 15 can be used for preventing or treating syringes.

Experimental Example 5: Effect of removing bad breath

In order to check the halitosis prevention or treatment effect of the compounds of Formulas 1 to 15, the test subjects were selected to perform a clinical experiment, and the control toothpaste and the experimental group toothpaste used in the clinical test were the same as the toothpaste of Experimental Example 2, respectively. Was prepared.

50 men and women without dental caries were selected as test subjects, and a cross-over test was performed on the control toothpaste and the test group toothpaste. Commercially available garlic powder was dispersed in water, left to stand for 24 hours, and then diluted so that the Halimeter measurement value was 700 ppb or more, and the diluted solution was used as a source of bad breath. The test subjects gargled with 15 ml of garlic powder diluted solution for 30 seconds, and after 1 minute, the degree of bad breath was measured with a halimeter, and then the control group used the control toothpaste, and the test group used the test group toothpaste, respectively, and brushed their teeth for 30 seconds to 1 minute. . After 1 minute, 5 minutes, and 30 minutes after brushing, the degree of halitosis was measured with a halimeter to measure the duration of halitosis suppression, and the results are shown in Table 8 below.

Bad breath removal effect (%) 1 minute 5 minutes 30 minutes Control 54.9 47.5 38.7 Albiflorin 95.1 89.6 82.2 Astragalloside I 94.2 89.7 84 Brassinolide 94.2 90 87.8 Eleuteroside E 96.1 87.8 85.4 Genthiopicrin 97.2 93.9 89.9 Gramine 94.9 88.9 83.4 Reenginein 95 88.3 83.8 Macrontoidine B 95.2 88.1 83.8 Neohesperidine dihydrochalcone 95.2 89.9 82 Obakunon 97.5 94.8 90 Oxysophocarpine 96 91.2 95.9 Scraleolide 97.6 94 91.4 Sophoricoside 95 85.6 80.1 Swaroside 95.1 88 84.4 Synephrine 96.1 89.5 85.2

As shown in Table 8, when compared to the control group, the experimental group using the toothpaste containing each compound of Formulas 1 to 15 had about 95% or more of bad breath removed at 1 minute after brushing, and 30 after brushing. Even after minutes, the halitosis removal rate was 80% or more, and the halitosis removal effect was far superior to that of the control group. Therefore, it was found that the compounds of Formulas 1 to 15 can be used for preventing or treating bad breath.

Claims (14)

Albiflorin (Albiflorin) or a quasi-drug composition for preventing or improving oral diseases comprising as an active ingredient a pharmaceutically acceptable salt thereof. The quasi-drug composition of 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 of claim 1, wherein the oral disease is a periodontal disease. The quasi-drug composition of claim 4, wherein the periodontal disease is periodontitis or gingivitis. The quasi-drug composition of claim 4, wherein the periodontal disease is caused by Porphyromonas gingivalis . The quasi-drug composition of claim 1, wherein the oral disease is toothache. The quasi-drug composition of claim 1, wherein the oral disease is syrini. The quasi-drug composition of claim 1, wherein the oral disease is bad breath. The quasi-drug composition of claim 1, wherein the quasi-drug is for oral use. The method of claim 10, wherein the formulation of the quasi-drug composition is at least one formulation selected from the group consisting of toothpaste, mouthwash, mouthwash, gum, candy, mouth spray, oral ointment, oral varnish, mouthwash, and gum massage cream. Which, quasi-drug composition. Albiflorin (Albiflorin) or a pharmaceutical composition for the prevention or treatment of oral diseases comprising a pharmaceutically acceptable salt thereof as an active ingredient. Albiflorin (Albiflorin) or a food composition for preventing or improving oral diseases comprising as an active ingredient food acceptable salts thereof. Albiflorin (Albiflorin) or an oral composition comprising an acceptable salt thereof as an active ingredient.