KR102288920B1 - Composition for prevention or treatment or oral disease - Google Patents

Abstract

The present invention relates to a composition for preventing or treating oral disease containing a natural compound, and more particularly, to a quasi-drug composition having an effect of preventing or improving dental caries, periodontal disease, toothache, sore throat and bad breath. The composition of the present invention has excellent antibacterial activity against dental caries and periodontal disease-causing bacteria, concentration-dependently inhibits PGE2, a pain and inflammation marker, gingivitis formation inhibitory effect, shirini symptom suppression effect, and bad breath removal effect. It has high utility as a quasi-drug composition for preventing or improving one or more oral diseases selected from the group consisting of dental caries, periodontal disease, sore throat 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, sore throat and bad breath. will be. In addition, the present invention relates to a pharmaceutical composition, a food composition, and a composition for oral use containing a natural compound 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 (cavities) and periodontal disease (periodontal disease) are diseases with a high incidence worldwide. It is known as the main factor that causes tooth loss and causes oral disease, and the causative factors of oral diseases are increasing due to changes in diet.

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

There are antibacterial agents as a method of inhibiting the proliferation of oral pathogens that live in plaque and cause dental caries, periodontal disease, bad breath and sore throat. It has been developed as an inhibitor and therapeutic agent for periodontal disease, pulp and apical infection.

However, since antibiotics can cause the appearance of resistant bacteria in the oral cavity and superinfection along with systemic side effects on our body, long-term use is difficult, and thus can only be used as a therapeutic agent. In addition, antibacterial agents used in mouthwashes include Sangquinarine, Listerine, Peroxide, and Chlorhexidine. The treatment effect for periodontal disease is not clear, and the price is expensive. Listerine contains alcohol as the main ingredient and has a slight bacteriostatic effect. There are some drawbacks that may appear. In addition, piroxide, which is recently added for whitening effect, is toxic to bacteria, but at the same time, it is also toxic to human tissues, so there is a problem in safety and sometimes bacteria resistant to pyroxide appear in bacteria. In addition, chlorhexidine is known to be the best known among agents for the prevention and treatment of periodontal disease as well as the inhibition of plaque formation. There are disadvantages in that it cannot be used for a long period of time for the purpose of treatment or, in particular, prevention, such as, as well as the problems shown, can cause mycosis mycosis, and has carcinogenic properties, limiting its use in pregnant women.

In addition, a compound artificially synthesized through a chemical reaction may exhibit side effects such as cytotoxicity or accumulation in the human body, so there is a need for studies on the pharmacological activity of natural compounds with a low possibility of side effects in terms of safety.

The present inventors have conducted research to derive a natural material excellent in the prevention and improvement of oral diseases such as dental caries, periodontal disease, toothache, sore throat, and bad breath without fear of side effects as described above. As a result, natural compounds that are safe and safe to use in the body have antibacterial effects on dental caries and periodontal disease-causing bacteria, toothache relief effect through PGE2 inhibitory effect, gingivitis formation inhibitory effect, shirin suppression effect, and bad breath removal effect. It has been found that the quasi-drug composition, pharmaceutical composition, food composition and oral composition using the same have been completed.

An object of the present invention is 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 pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a composition for oral use 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 antibacterial activity against dental caries and periodontal disease-causing bacteria, concentration-dependently inhibits PGE2, a pain and inflammation marker, gingivitis formation inhibitory effect, Shirin symptom suppression effect, and bad breath removal effect. It is excellent and has high utility as a quasi-drug composition for preventing or improving at least one oral disease selected from the group consisting of dental caries, periodontal disease, sore throat and bad breath. In addition, the composition comprising 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, there is provided a food composition for preventing or improving oral diseases comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

As another aspect of the present invention, there is provided a composition for oral use 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 living organisms such as microorganisms, plants, and animals, and can be extracted, separated, or purified therefrom, and as specific examples of the natural compound, albiflorin, astragal Astragaloside I, Brassinolide, Eleutheroside E, Gentiopicrin, Gramine, Liensinine, Macrontoidine B ( Macranthoidin B), Neohesperidin dihydrochalcone, Obacunone, Oxysophocarpine, Sclareolide, Sophoricoside, Sweroside , Synephrine, and the like, but is not limited thereto.

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

In the present invention, the astragaloside I (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 C 28} H ₄₈ O ₆ and a molecular weight of 480.6.

In the present invention, the eleutheroside E (Eleutheroside E) is _{an organic compound represented by Formula 4 and having a molecular formula C 34} H ₄₆ O ₁₈ and a molecular weight of 742.7.

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

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

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

In the present invention, the macroanthoidin B (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 (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 (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 (Oxysophocarpine) is _{an organic compound represented by Chemical Formula 11 and having a molecular formula 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 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 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 C 16} H ₂₂ O ₉ and a molecular weight of 358.3.

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

The present invention is not particularly limited to a method for obtaining the compound, and may be 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 within 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 provides at least one oral cavity selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, sore throat, and bad breath comprising the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. It is possible to provide a quasi-drug composition for preventing or improving disease.

The 'natural compound' is the same 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 rear palate. In the present invention, the oral disease is a concept that includes all diseases occurring in the oral cavity regardless of the pathology, and non-limiting examples of the oral disease include dental caries, periodontal disease (periodontitis or gingivitis), toothache, sore throat, bad breath and the like.

In the present invention, the term “dental cavities” is an infectious disease caused by bacteria living on the tooth surface, also called caries, and shows a symptom in which the hard tissue of the tooth is eroded and defective. Specifically, the milky-white, translucent and hard material that covers the surface of the tooth head and protects the tooth dentin is called tooth enamel or enamel. Dental enamel is damaged and tooth decay occurs. The main cause of dental caries is dental plaque, which is a bacterial film formed on the surface of teeth. Oral microorganisms such as ( Streptococcus sobrinus ) and Streptococcus mutans attach to form a biofilm to form dental plaque and become thicker by Fusobacterium ) lose Dental caries of the present invention is included regardless of the type of bacteria causing dental caries, but specifically, Streptococcus mutans , Streptococcus sanguinis , Streptococcus sanguinis, Streptococcus sobrinus ), Streptococcus ratti , Streptococcus criceti , Streptococcus anginosus ( Streptococcus anginosus ) and lactic acid bacteria may be uniform at least one selected from the group consisting of, more specifically, Streptococcus may be mutans.

The Streptococcus mutans is a type of streptococcus, a gram-positive bacteria, and is also called a caries bacteria. The Streptococcus mutans proliferates only on the surface of the teeth, but the primary teeth are not completed until around 30 months of age. Therefore, it is difficult for mutans to proliferate until this time, as it did after infancy. If mutans bacteria are not infected from the mouth of adults during infancy and other oral bacteria are established in the mouth, it is difficult for mutans bacteria to enter the already balanced oral ecosystem, and the probability of cavities throughout life after infancy is significantly higher. will be lowered If the causative bacteria have already been transmitted through the mouth of adults, frequent gargling and keeping the inside of the mouth clean will help prevent tooth decay. However, once mutans is established in the oral cavity, eradication of mutans is impossible.

In one embodiment of the present invention, as a result of measuring the size of the growth inhibition ring after inoculating the disk containing the natural compound of the present invention in the medium streptococcus mutans smeared, growth inhibition in the case of the experimental group including the compound It was confirmed that the ring diameter was 10.0 mm or more and exhibited significantly excellent antibacterial activity against Streptococcus mutans, so that the composition containing the natural compound could be used for preventing or improving dental caries (Table 2).

In the present invention, "periodontal disease" is a disease in which the gingiva, periodontal ligament, and bone tissue supporting the teeth are inflamed, and is often referred to as wind teeth. Depending on the severity of the disease, gingivitis and periodontitis divided into It is a relatively light and quick form of periodontal disease, and the form limited only to the gums, that is, the soft tissue is called gingivitis, and when the inflammation has progressed to the gums and around the gums, it is called periodontitis. There is a V-shaped gap between the gingiva (gum) and teeth. Oral pathogens attack the lower part of the gum line of the sulcus and release lipopolysaccharide (LPS), which is an inflammatory stimulant. Inflammation occurs, such as swelling and bleeding of the gums, which damages the periodontal ligaments and adjacent tissues. As periodontitis progresses, periodontal ligaments and even alveolar bone are damaged and eventually teeth are lost. Nutritional deficiencies such as protein and vitamins, hormonal disorders such as pregnancy or diabetes, smoking, and acquired immunodeficiency syndrome (AIDS) can aggravate 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 ) Can be uniform at least one selected from the group consisting of, more specifically, P. It could be Bali.

The Porphyromonas gingivalis is a type of Bacteroide, a Gram-negative bacterium, and an anaerobic bacterium. The Porphyromonas gingivalis is found in the oral cavity where periodontal disease has occurred, and in addition, it is also found in the upper gastrointestinal tract, respiratory tract and colon. In patients with chronic periodontal disease, collagen is degraded by the collagenase enzyme of the bacteria, and the bacteria can invade gingival fibroblasts and survive even under a significant 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, as a result of measuring the size of the growth-inhibiting ring after inoculating the disk containing the natural compound of the present invention in a medium smeared with P. gingivalis, growth in the case of the experimental group containing the compound It was confirmed that the low ring diameter was 10.0 mm or more and exhibited significantly excellent antibacterial activity against P. gingivalis, and the composition containing the compound could be used for preventing or improving periodontal disease (Table 2).

In addition, in one embodiment of the present invention, as a result of conducting clinical trials by selecting test subjects with gingival inflammation, the experimental group using the experimental group toothpaste containing the compound has excellent gingival inflammation inhibitory effect, even after 6 months have elapsed It was confirmed that the gingivitis inhibitory effect was maintained by maintaining the normal bleeding state, and the composition containing the natural compound could be used for preventing or improving periodontal disease including gingivitis (Table 4).

In the present invention, “tooth pain” refers to pain in the teeth when eating sweet food or very cold or hot food. Pain is also included. It is usually painful when chewing, swollen gums, and a foul-smelling discharge. 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 and the pain occurs when the nerves in the tooth are deeply rotted. Pain is caused, and when the tooth is broken or cracked, the tooth cracks when it comes in contact with cold food or when it is bitten strongly, which stimulates the nerve and causes pain. In the case of pulpitis, in the early stages, pain is felt when cold food is touched, and when it is more advanced, pain is felt by hot food. Pain is caused by inflammation of

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 a concentration-dependent effect of inhibiting PGE2 (Table 5).

In the present invention, the term “single” refers to hypersensitive dentine, and the symptom of dentine hyperesthesia refers to dentine hyperesthesia. This symptom is a sensitive sensation when the exposed dentin of the tooth comes into contact with cold air or irritating food, and it is present in 60 to 98% of adults with periodontal disease. Painful tooth symptoms occur when teeth are dented on the gum side due to incorrect brushing habits, excessive occlusal force, or dissolution by acid, poor oral hygiene, periodontal treatment, restoration treatment, or tooth dissolution due to acidification may appear Shirin is the root cause of the symptoms and it appears when many tubules in the dentin of the tooth are exposed to the outside. there is. The symptoms of sore throat can vary from mild symptoms to intense and persistent pain, and because teeth do not regenerate due to the nature of the tooth, taking painkillers or anti-inflammatory drugs is not a fundamental solution to the pain. A sore throat symptom may appear throughout the tooth, or it may appear limited to a specific area such as the maxilla or mandible, or the right or left side. The most common areas vary depending on the cause, but mainly canine teeth and small molars.

In one embodiment of the present invention, as a result of conducting clinical trials by selecting test subjects with dentin hypersensitivity teeth, in the case of the experimental group using the experimental group toothpaste containing the compound of the present invention, shirin has excellent symptom suppression effect, It was confirmed that the composition comprising the natural compound can be used for prophylactic or amelioration purposes (Table 7).

In the present invention, “bad breath” is a smell derived from the oral cavity and adjacent organs, and 85 to 90% of bad breath originates from the oral cavity, in particular, from the back of the tongue. The main component of bad breath is 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 for bacteria to live continuously. Although the production of volatile sulfur compounds by anaerobic bacteria is the most important cause of bad breath, it is also caused by oral diseases such as dental caries, periodontitis, and dry mouth. Many types of anaerobic bacteria are involved in the occurrence of bad breath, and a non-limiting example of the bacteria causing 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 performing a clinical test on a test subject without dental caries, the effect of removing bad breath was excellent in the experimental group using the experimental group toothpaste containing the natural compound of the present invention, the compound It was confirmed that the composition comprising the 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 use. Components included in the quasi-drug composition of the present invention may include components commonly used in oral quasi-drug compositions in addition to the active ingredients as an active ingredient, for example, an abrasive, a wetting agent, a binder, a foaming agent, a sweetener, a preservative, an active ingredient, a flavor agents, dyes, solvents, brighteners, solubilizers or pH adjusters.

The quasi-drug composition for oral use of the present invention may be prepared in any formulation conventionally prepared in the art, for example, toothpaste, mouthwash, mouthwash, gum, candy, oral spray, oral ointment, oral varnish , oral gargle and gum massage cream, but are not limited thereto.

As an example, when the quasi-drug composition for oral use of the present invention is a toothpaste formulation, a wetting agent, an abrasive, a binder, a foaming agent, a flavoring agent, a sweetener, a coloring agent, a preservative, an active ingredient, a solvent, a pH adjusting agent, etc. may be included.

The humectant is used to make the powder of the toothpaste component into a paste and prevent the toothpaste from solidifying in the air. Glycerin, sorbit solution, propylene glycol, polyethylene glycol, etc. are mixed alone or 2 or more types are mixed to form 1 to 60 weight of the total weight of the composition. %, specifically 10 to 50 wt% may be used.

The foaming agent diffuses the toothpaste in the oral cavity to enhance the cleaning effect, and acts as a surfactant to clean oral contamination. A surfactant such as sodium lauryl sulfate, sodium lauryl sarcosinate, sodium alkyl sulfosuccinate, and sucrose fatty acid ester is used alone. Or 0.5 to 10% by weight, specifically 0.5 to 5% by weight of the total weight of the composition by mixing two or more types may be used.

The binder is to prevent separation between the powder and liquid components in the toothpaste. Cellulose derivatives such as sodium carboxymethyl cellulose, methyl cellulose, and hydroxypropyl cellulose and sodium alginate, carrageenan, xanthan gum, etc. are mixed alone or by mixing two or more types. 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 article removes the attachment of the tooth surface rather to wound the tooth surface, and calcium carbonate as nadorok the original tooth polish (CaCO _3), calcium secondary phosphate _{(CaHPO 4, CaHPO 4 2H 2} O), silica (SiO ₂ 2H ₂ O), aluminum hydroxide (Al(OH) ₃ ), potassium pyrophosphate, magnesium carbonate, etc. alone or by mixing two or more types, 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 freshness and odor to the toothpaste. Peppermint oil, spearmint oil, menthol, and the like may be mixed alone or in a mixture of 0.01 to 60% by weight of the total weight of the composition, specifically 0.01 to 5% by weight may be used.

The sweetener is to remove the unpleasant taste caused by the toothpaste raw material and to improve the refreshing feeling. Saccharinic acid, aspartame, xylitol, licorice acid, etc. are mixed alone or in a mixture of two or more of 0.01 to 60% by weight of the total weight of the composition, specifically 0.01 to 5% by weight may be used.

The active ingredients are fluoride, zinc chloride, chlorhexidine, aminocaproic acid, tranexamic acid, cetylpyridium chloride, pyridoxine chloride, Triclosan, tocopherol acetate, sodium monofluorophosphate, etc. can be used alone or in combination of two or more. In the present invention, the compound may be used as an additional active ingredient.

The quasi-drug composition for oral cavity of the present invention may be used alone or in combination, or may be used in combination with other quasi-drug compositions for oral use 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 provides a pharmaceutical composition for preventing or treating one or more oral diseases selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, sore throat, and bad breath comprising the natural compound as an active ingredient can provide The natural compound, oral disease, dental caries, periodontal disease, toothache, sore throat and bad breath are the same as described above.

The pharmaceutical composition of the present invention is in the form of tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, aerosols, sterile injection 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, etc., and these solid preparations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. can be In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, syrups, etc., and various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. in addition to commonly used simple diluents such as water and liquid paraffin. can be used

Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Vegetable oils such as propylene glycol, polyethylene glycol, and olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspensions.

In addition, the pharmaceutical composition of the present invention may further include a carrier, excipient or diluent. Carriers, excipients or diluents include lactose, dextrose, 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, methyl hydroxy benzoate, propyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate, silicon dioxide, etc. may be used. there is.

The specific dosage of the pharmaceutical composition according to the present invention depends on factors such as the formulation method, the patient's condition and weight, the patient's sex, age, degree of disease, drug form, administration route and period, excretion rate, reaction sensitivity, etc. It can be variously selected 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 may be administered to mammals such as rats, mice, livestock, and humans through various routes. Any mode of administration may be contemplated and may be administered, for example, by oral, intravenous, intramuscular or subcutaneous injection.

As 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, sore throat, and bad breath comprising the compound as an active ingredient can do. The natural compound, oral disease, dental caries, periodontal disease, toothache, sore throat and bad breath are the same as described above. The food composition may be used in the form of health functional food, but is not limited thereto.

The natural compound or a pharmaceutically acceptable salt thereof contained in the food composition of the present invention may be included in the form of animals and plants containing the compound, an extract thereof, a fraction thereof, or a processed product thereof. In addition, the composition may include a food pharmaceutically acceptable food supplement additive in addition to the active ingredient.

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

The food composition of the present invention may include a health functional food. In the present invention, "health functional food" refers to a food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. using raw materials or ingredients useful for the human body. Here, the term “functionality” refers to obtaining useful effects for health purposes such as regulating 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 manufacture, it can be prepared by adding raw materials and components commonly added in the art. In addition, if the formulation of the health functional food is also recognized as a health functional food, it may be manufactured without limitation. The food composition of the present invention can be prepared in various forms, and unlike general drugs, it has the advantage that there are no side effects that may occur during long-term administration of the drug using food as a raw material, and has excellent portability, Health functional food can be consumed as a supplement to prevent or improve oral diseases.

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

Modes for carrying out the invention

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

Experimental Example 1: Antibacterial effect on bacteria causing dental caries and periodontitis

An antibacterial activity experiment was performed to confirm the preventive or therapeutic effect of the compounds of Formulas 1 to 15 on dental caries and periodontitis. Antibacterial activity test by using the paper disc test method using Streptococcus mutans , the representative bacteria causing dental caries, and Porphyromonas gingivalis , the representative bacteria causing periodontal disease, to confirm the effect of inhibiting the growth of oral pathogens was carried out.

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

strain optimum condition Gram staining strain name temperature badge characteristics Gram (+) Streptococcus mutans 37 BHI facultative anaerobic Gram (-) Porphyromonas gingivalis 37 TSA Hemin Menadione Badge anaerobic

Results of measurement of antibacterial activity against oral pathogens of the compounds of Formulas 1 to 15 Growth inhibition ring diameter (mm) Streptococcus mutans Porphyromonas gingivalis unprocessed - (Growth is not inhibited) - (Growth is not inhibited) Albiflorin 10.0 9.9 Astragaloside I 10.1 10.6 brassinolide 10.1 10.1 Eleuteroside E 10.5 9.9 Genthiopicrine 11.3 11.0 Grameen 10.6 10.1 Reengine 10.6 10.0 macrantoidine B 10.5 10.2 neohesperidin dihydrochalcone 10.5 10.2 Obakunon 11.8 12.0 oxysopocarpine 10.3 10.8 scrareolide 11.8 12.0 Sophoricoside 10.1 9.9 Sweroside 11.0 10.2 Synephrine 9.5 9.9

As shown in Table 2, compared to the untreated group, the group treated with the compounds of Formulas 1 to 15 had a growth-inhibiting ring diameter of 9.5 mm or more for the two oral pathogens, Streptococcus mutans and foreskin. It exhibited a fairly excellent antibacterial activity against Romonas gingivalis. Therefore, it was found that the compounds of Formulas 1 to 15 can be used for preventing or treating dental caries or periodontal disease. Experimental Example 2: Gingivitis formation inhibitory effect

In order to confirm the gingivitis prevention or treatment effect of the compounds of Formulas 1 to 15, a clinical trial was performed by selecting a test subject group.

First, sodium carboxymethyl cellulose, sodium lauryl sulfate, glycerin, colloidal silicon dioxide, silicas, sodium cocoyl ethionate sodium, dodicin and sweeteners, fragrances, and coloring agents, which are generally used in the manufacture of toothpaste, are used. to make a control toothpaste, and 0.01 wt% of one of the compounds of Formulas 1 to 15 was contained in the control toothpaste to prepare an experimental group toothpaste.

In order to select the subjects for the experiment, precise oral examinations were conducted for patients with gingivitis with even dentition and no missing teeth, from 30 to 50 years of age by age, at 10-year intervals for 30 patients by gender. After screening, 60 patients were divided into clinical trials for the treatment effect of gingival inflammation as follows.

Specifically, the experimental group was divided into a control group and an experimental group, and the control group was instructed to use the prepared control toothpaste 3 times a day before going to sleep after 2 hours after eating, and the experimental group used the prepared experimental group toothpaste 3 times a day at the same time educated to do Afterwards, tooth brushing was performed to score the initial gingivitis index, and the control group used the prepared control toothpaste and the experimental group used the prepared experimental group toothpaste. After 1 week, 1 month, 3 months and 6 months, oral examination was performed. The gingivitis index was examined. The gingivitis index is measured by inserting a periodontal probe into the gingival sulcus, burning the probe around each tooth without applying any force, and measuring the bleeding state after 30 seconds has passed. Scores were recorded accordingly, and the results are shown in Table 4.

Based on the gingivitis index score Contents 0 points bleeding-free 1 point normal bleeding 2 points glandular bleeding 3 points Triangular hemorrhage in the interdental region 4 points whole gingival bleeding

Gingivitis Inhibitory Effect 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 Astragaloside 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 Genthiopicrine 1.05 1.05 1.06 1.08 1.08 Grameen 1.04 1.07 1.08 1.10 1.12 Reengine 1.05 1.04 1.08 1.11 1.14 macrantoidine B 1.04 1.06 1.10 1.12 1.14 neohesperidin dihydrochalcone 1.04 1.05 1.08 1.10 1.12 Obakunon 1.04 1.04 1.06 1.06 1.07 oxysopocarpine 1.05 1.07 1.09 1.13 1.15 scrareolide 1.06 1.06 1.07 1.08 1.09 Sophoricoside 1.06 1.08 1.09 1.11 1.14 Sweroside 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, compared with the control group, the experimental group using a toothpaste containing one of the compounds of Formulas 1 to 15 maintained the normal bleeding state even after 6 months had elapsed, and the gingivitis inhibitory effect was maintained. . Accordingly, 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 preventive or therapeutic effect of the compounds of Formulas 1 to 15, the inhibitory effect of PGE2, known as a pain and inflammation marker, was confirmed.

First, macrophages were inoculated in DMEM medium containing 10% FBS at a ^{concentration of 1.5 X 10 5} cells/ml and cultured in a 24 well plate at 37° C. and 5% CO _{2 conditions for 24 hours.} Then, 1 μg/ml of LPS, which is an inflammation-inducing stimulant, and each of the compounds of Formulas 1 to 15 were treated at different concentrations and further cultured for 24 hours, PGE2 ELISA assay kit (Thermo SCIENTIFIC) was purchased and the supernatant was used for 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 Astragaloside I 79 58 brassinolide 51 23 Eleuteroside E 56 37 Genthiopicrine 26 9 Grameen 72 42 Reengine 61 34 macrantoidine B 60 37 neohesperidin dihydrochalcone 26 9 Obakunon 37 16 oxysopocarpine 79 50 scrareolide 42 17 Sophoricoside 70 46 Sweroside 59 38 Synephrine 80 59

As shown in Table 5, when compared to the group treated with only LPS, it was confirmed that all of the compounds of Formulas 1 to 15 exhibited a concentration-dependent PGE2 inhibitory effect, thereby confirming that the preventive and therapeutic effects of toothache were excellent. Experimental Example 4: Inhibitory effect of sirin

In order to confirm the preventive or therapeutic effect of the compounds of Formulas 1 to 15, clinical trials were conducted by selecting test subjects. each was prepared.

The subjects of the experiment were 40 volunteers with dentin hypersensitivity teeth 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 ages ranged from 20 to 50 years old. Subjects were not allowed to know the contents of the toothpaste, and the total duration of the experiment was 2 weeks.

The experiment was performed by measuring the reaction of the test subject after applying a temperature stimulus. Before carrying out the experiment, check the sensitive area of the dentin hypersensitivity tooth of each test subject in advance, drop cold water of about 5°C with a dropper on the sore area of the tooth and rate it according to the criteria shown in Table 6 below The control toothpaste and the experimental group were graded by dropping the experimental group toothpaste 3 times a day for 2 weeks, and then dropping cold water at about 5°C again with a dropper after 2 weeks. For statistical processing, the stimulation scores before and 2 weeks after the experiment were tested using the paired Student-t test, and the response scores after 2 weeks to the temperature stimulation are shown in Table 7 below.

Rating criteria of test subjects after stimulation score Contents 0 points no discomfort 1 point Slightly uncomfortable or sore 2 points chill a lot 3 points sick.

degree of inhibition of sirin 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 Astragaloside 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 Genthiopicrine 2.14±0.17 1.73±0.11 *p<0.05 Grameen 2.13±0.21 1.90±0.10 *p<0.05 Reengine 2.14±0.13 1.89±0.17 *p<0.05 macrantoidine B 2.14±0.16 1.88±0.20 *p<0.05 neohesperidin dihydrochalcone 2.13±0.08 1.85±0.12 *p<0.05 Obakunon 2.14±0.18 1.73±0.10 *p<0.05 oxysopocarpine 2.13±0.14 1.89±0.02 *p<0.05 scrareolide 2.15±0.10 1.78±0.09 *p<0.05 Sophoricoside 2.13±0.14 1.84±0.20 *p<0.05 Sweroside 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 compound of Formulas 1 to 15 passed 2 weeks. After shirin this phenomenon was suppressed. Accordingly, it was found that the compounds of Chemical Formulas 1 to 15 can be used for preventing or treating Shirin.

Experimental Example 5: Effect of removing bad breath

In order to confirm the effect of preventing or treating halitosis of the compounds of Formulas 1 to 15, clinical trials were conducted by selecting test subjects, and the control toothpaste and the experimental group toothpaste used in the clinical trial were used in the same manner as the toothpaste of Experimental Example 2, respectively. prepared.

50 men and women without dental caries were selected as test subjects, and a cross-over test was performed on the toothpaste of the control group and the toothpaste of the experimental group. Commercially available garlic powder was dispersed in water, allowed 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 measuring the degree of bad breath with a Hallimeter 1 minute later, the control group used the control toothpaste and the experimental group used the toothpaste of the experimental group, respectively, for 30 seconds to 1 minute. . After 1 minute, 5 minutes, and 30 minutes after brushing teeth, the degree of bad breath was measured with a hallimeter to determine whether or not the inhibition of bad breath was continued, and the results are shown in Table 8 below.

Bad breath removal effect (%) 1 min 5 minutes 30 minutes control 54.9 47.5 38.7 Albiflorin 95.1 89.6 82.2 Astragaloside I 94.2 89.7 84 brassinolide 94.2 90 87.8 Eleuteroside E 96.1 87.8 85.4 Genthiopicrine 97.2 93.9 89.9 Grameen 94.9 88.9 83.4 Reengine 95 88.3 83.8 macrantoidine B 95.2 88.1 83.8 neohesperidin dihydrochalcone 95.2 89.9 82 Obakunon 97.5 94.8 90 oxysopocarpine 96 91.2 95.9 scrareolide 97.6 94 91.4 Sophoricoside 95 85.6 80.1 Sweroside 95.1 88 84.4 Synephrine 96.1 89.5 85.2

As shown in Table 8, 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 gargling, and 30% after gargling. Even after minutes elapsed, the rate of removal of bad breath was more than 80%, and the effect of removing bad breath was significantly superior to that of the control group. Accordingly, it was found that the compounds of Formulas 1 to 15 can be used for preventing or treating bad breath.

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 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 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 of claim 1, wherein the oral disease is toothache. The quasi-drug composition according to claim 1, wherein the oral disease is Shirin. The quasi-drug composition according to claim 1, wherein the oral disease is bad breath. The composition of claim 1, wherein the quasi-drug is for oral use. 11. The method of claim 10, wherein the formulation of the quasi-drug composition is toothpaste, mouthwash, mouthwash, gum, candy, oral spray, oral ointment, oral varnish, oral gargle, and one or more formulations selected from the group consisting of gum massage cream The quasi-drug composition. 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 comprising albiflorin or a pharmaceutically acceptable salt thereof as an active ingredient. As an antibacterial oral composition comprising Albiflorin or an acceptable salt thereof as an active ingredient,
The oral composition is Streptococcus mutans (Streptococcus mutans) or Porphyromonas gingivalis (Porphyromonas gingivalis) will have an inhibitory activity against, the oral composition for antibacterial.