Composition for preventing or treating oral diseases

Abstract

To provide a composition for preventing or treating oral diseases, comprising a natural compound.SOLUTION: The present invention relates to a quasi-drug composition for preventing or treating oral diseases, comprising Sclareolide or a pharmaceutically acceptable salt thereof as an active ingredient, where the oral diseases include toothache and hyperesthesia. The composition of the present invention has excellent antimicrobial activity against bacteria causing dental caries and periodontal disease; suppresses PGE2, which is pain and inflammation marker, in a concentration-dependent manner; has excellent effects for suppressing gingivitis formation, suppressing the symptoms of sensitive teeth, and eliminating halitosis; and thus has a high utilization as a quasi-drug composition for preventing or alleviating one or more oral diseases selected from the group consisting of dental caries, periodontal disease, hyperesthesia, and halitosis. Furthermore, the composition of the present invention is useful as a pharmaceutical composition and a food composition.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for preventing or treating oral diseases, which contains a natural compound as an active ingredient, and more specifically to a quasi-drug composition that has the effect of preventing or ameliorating dental caries, periodontal disease, toothache, hypersensitivity, and bad breath. The present invention also relates to a pharmaceutical composition, a food composition, and an oral composition that contain the natural compound as an active ingredient. [Background technology]

[0002] Healthy teeth are said to be one of the five blessings, as they are an important factor in determining quality of life. Among oral diseases, dental cavities and periodontal disease have a high incidence rate worldwide and are known to cause various clinical symptoms such as pain, impaired chewing function, destruction of periodontal tissue, bad breath, and hypersensitivity, and are known to be major factors leading to tooth loss. In addition, the causative factors of oral diseases are currently increasing due to changes in dietary habits.

[0003] The human oral cavity is known to harbor approximately 600 to 800 species of microorganisms, which are controlled by enzymes such as lysozyme contained in saliva. However, the oral environment, rich in nutrients and moisture, provides favorable conditions for the growth of microorganisms, and the tongue and dental plaque provide ideal habitats for microorganisms. Some of these microorganisms are opportunistic pathogens that cause diseases such as dental caries, periodontal disease, and tooth sensitivity (dentin hypersensitivity), as well as bad breath.

[0004] Antibacterial agents are used as a method for inhibiting the growth of oral pathogenic bacteria that live in dental plaque and cause caries, periodontal disease, bad breath, and tooth sensitivity. Various antibacterial preparations, including antibiotics that have bactericidal and bacteriostatic effects against oral pathogenic bacteria, have been developed as agents for inhibiting and treating tooth decay, periodontal disease, and pulp and root-end infections.

[0005] However, antibiotics have the drawback of being used solely as a treatment, as they can cause systemic side effects in the human body, as well as the emergence of resistant bacteria and superinfection in the oral cavity, making their long-term use difficult. Furthermore, antibacterial preparations used in oral rinses include sanguinarine, Listerine, peroxide, and chlorhexidine. However, sanguinarine has the drawback of being expensive, with its effectiveness against oral bacteria and periodontal disease unknown. Listerine, which contains alcohol as its main ingredient, has a slight bacteriostatic effect, but only exerts a temporary effect in the oral cavity, and long-term use can cause tissue damage. Furthermore, peroxide, which has recently been added for whitening purposes, is toxic to bacteria and also to human tissues, raising safety concerns and potentially leading to the emergence of peroxide-resistant bacteria. Furthermore, although chlorhexidine is known to be the most effective agent for preventing and treating periodontal disease among conventional preparations, it can irritate tissues, cause tissue discoloration and degeneration, and has a particularly strong, pungent taste and odor. It can also induce bacterial replacement and is carcinogenic, so its use is restricted in pregnant women. This means that it cannot be used for long-term treatment or prevention.

[0006] Furthermore, compounds artificially synthesized through chemical reactions can cause side effects such as cytotoxicity or accumulation in the human body, so from a safety perspective, research is needed into the pharmacological activity of natural compounds that are less likely to cause side effects. Summary of the Invention [Problem to be solved by the invention]

[0007] The present inventors have conducted extensive research to find natural materials that are free from such side effects and have excellent effects in preventing and improving oral diseases such as dental caries, periodontal disease, toothache, hypersensitivity, and bad breath. As a result, they have discovered that natural compounds that are safe for the human body and can be used with peace of mind exhibit antibacterial effects against bacteria that cause dental caries and periodontal disease, toothache relief through PGE2 inhibitory effects, gingivitis onset suppression effects, hypersensitivity suppression effects, and bad breath elimination effects, and have completed quasi-drug compositions, pharmaceutical compositions, food compositions, and oral compositions that utilize these natural compounds. [Means for solving the problem]

[0008] An object of the present invention is to provide a quasi-drug composition for preventing or ameliorating oral diseases, which contains a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0009] Another object of the present invention is to provide a pharmaceutical composition for preventing or treating oral diseases, which comprises a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0010] A further object of the present invention is to provide a food composition for preventing or improving oral diseases, which contains a natural compound or a nutritively acceptable salt thereof as an active ingredient.

[0011] A further object of the present invention is to provide an oral composition containing a natural compound or an acceptable salt thereof as an active ingredient. [Effects of the Invention]

[0012] Quasi-drug compositions containing the natural compounds of the present invention or pharmaceutically acceptable salts thereof as active ingredients are effective in preventing or ameliorating oral diseases. Specifically, the compositions of the present invention have excellent antibacterial activity against bacteria that cause dental caries and periodontal disease, concentration-dependently suppress PGE2, a pain and inflammation marker, and are effective in suppressing the onset of gingivitis, suppressing hypersensitivity symptoms, and eliminating bad breath. These compositions are highly useful as quasi-drug compositions for preventing or ameliorating at least one oral disease selected from the group consisting of dental caries, periodontal disease, hypersensitivity, and bad breath. Furthermore, compositions containing the natural compounds of the present invention are useful as pharmaceutical compositions and food compositions. DETAILED DESCRIPTION OF THE INVENTION

[0013] In order to solve the above problems and achieve the above objects, one aspect of the present invention provides a quasi-drug composition for preventing or ameliorating oral diseases, which contains a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0014] Another aspect of the present invention provides a pharmaceutical composition for preventing or treating oral diseases, comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0015] Yet another aspect of the present invention provides a food composition for preventing or improving oral diseases, which comprises a natural compound or a nutrient-acceptable salt thereof as an active ingredient.

[0016] Yet another aspect of the present invention provides an oral composition comprising a natural compound or an acceptable salt thereof as an active ingredient.

[0017] The present invention provides a quasi-drug composition containing a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0018] The term "natural compound" refers to a substance that is produced directly from an organism such as a microorganism, plant, or animal, and can be extracted, separated, or purified therefrom. Specific examples of the natural compound include, but are not limited to, albiflorin, astragaloside I, brassinolide, eleutheroside E, gentiopicrin, gramine, liensinine, macranthoidin B, neohesperidin dihydrochalcone, obacunone, oxysophocarpine, sclareolide, sophoricoside, sweroside, and synephrine.

[0019] [ka]

[0020] The albiflorin in the present invention is represented by chemical formula 1 and has molecular formula C 23 H 28 O 11 , an organic compound with a molecular weight of 408.4.

[0021] [ka]

[0022] The astragaloside I in the present invention is represented by chemical formula 2 and has molecular formula C 45 H 72 O 16 , an organic compound with a molecular weight of 869.0.

[0023] [ka]

[0024] The brassinolide in the present invention is represented by chemical formula 3 and has molecular formula C 28 H 48 O6, an organic compound with a molecular weight of 480.6.

[0025] [ka]

[0026] The eleutheroside E in the present invention is represented by chemical formula 4 and has molecular formula C 34 H 46 O 18 , an organic compound with a molecular weight of 742.7.

[0027] [ka]

[0028] The gentiopicrin of the present invention is represented by chemical formula 5 and has molecular formula C 16 H 20 O9, an organic compound with a molecular weight of 356.3.

[0029] [ka]

[0030] The gramine in the present invention is represented by Chemical Formula 6 and has the molecular formula C 11 H 14 N2 is an organic compound with a molecular weight of 174.

[0031] [ka]

[0032] The liensinine in the present invention is represented by chemical formula 7 and has molecular formula C 37 H 42 N2O6 is an organic compound with a molecular weight of 610.7.

[0033] [ka]

[0034] The macranthoidin B in the present invention is represented by chemical formula 8 and has molecular formula C 65 H 106 O 32 , an organic compound with a molecular weight of 1399.5.

[0035] [ka]

[0036] The neohesperidin dihydrochalcone in the present invention is represented by chemical formula 9, and has molecular formula C 28 H 36 O 15 , an organic compound with a molecular weight of 612.5.

[0037] [ka]

[0038] The obacunone in the present invention is represented by chemical formula 10 and has the molecular formula C 25 H 30 O7, an organic compound with a molecular weight of 455.

[0039] [ka]

[0040] The oxysophocarpine in the present invention is represented by chemical formula 11 and has the molecular formula C 15 H 22 N2O2 is an organic compound with a molecular weight of 262.4.

[0041] [ka]

[0042] The sclareolide in the present invention is represented by chemical formula 12, and has the molecular formula C 16 H 26 O2 is an organic compound with a molecular weight of 250.3.

[0043] [ka]

[0044] The sophoricoside in the present invention is represented by chemical formula 13 and has the molecular formula C 21 H 20 O 10 , an organic compound with a molecular weight of 432.

[0045] [ka]

[0046] The sweroside in the present invention is represented by chemical formula 14 and has the molecular formula C 16 H 22 O9, an organic compound with a molecular weight of 358.3.

[0047] [ka]

[0048] The synephrine in the present invention is represented by chemical formula 15, and has the molecular formula CH 13NO2 is an organic compound with a molecular weight of 167.2.

[0049] The method for obtaining the compound in the present invention is not particularly limited, and the compound may be chemically synthesized by a method known in the art, or a commercially available substance may be used.

[0050] The compounds of the present invention may exist in unsolvated as well as solvated forms. The compounds of the present invention may also exist in crystalline or amorphous form, and all such physical forms are included in the present invention.

[0051] One aspect of the present invention provides a quasi-drug composition for preventing or ameliorating oral diseases, which comprises the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0052] More specifically, the present invention provides a quasi-drug composition for preventing or ameliorating at least one oral disease selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, hypersensitivity, and bad breath, which comprises the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0053] The "natural compounds" are as described above.

[0054] In the present invention, "oral disease" refers to various diseases occurring in the oral region, and the oral region refers to the space inside the mouth that extends from the lips in the front to the pharynx at the isthmus in the back. The oral disease in the present invention is a concept that includes all diseases occurring in the oral cavity, regardless of their symptoms, and examples of the oral disease include, but are not limited to, dental caries, periodontal disease (periodontitis or gingivitis), toothache, hypersensitivity, and halitosis.

[0055] In this invention, "dental cavities" refers to an infectious disease caused by bacteria living on the tooth surface, also known as tooth decay, which is a symptom of erosion and loss of dental hard tissue. Specifically, the milky white, translucent, hard substance that covers the upper surface of the tooth and protects the dentin is called enamel, but oral pathogenic bacteria living in the mouth break down sugars, starches, etc., producing acids that damage the dental enamel and cause tooth decay. The main cause of dental caries is dental plaque, a bacterial film that forms on the surface of teeth. Saliva forms a sticky thin film on the teeth, and oral microorganisms such as Streptococcus sobrinus and Streptococcus mutans, which are types of streptococcus, attach to it to form a biofilm, which then forms dental plaque, which is further thickened by Fusobacterium. The caries-causing bacteria in the present invention include all caries-causing bacteria regardless of their type, and specifically at least one bacterium selected from the group consisting of Streptococcus mutans, Streptococcus sanguinis, Streptococcus sobrinus, Streptococcus ratti, Streptococcus criceti, Streptococcus anginosus, and lactic acid bacteria, and more specifically Streptococcus mutans.

[0056] Streptococcus mutans is a gram-positive bacterium of the streptococcus family, also known as the caries-causing bacterium. Streptococcus mutans grows only on the surface of teeth, but primary teeth are not fully formed until around 30 months of age. Therefore, it is difficult for Streptococcus mutans to proliferate until this age, as it does in infancy. If other oral bacteria colonize the mouth without infection with Streptococcus mutans from an adult's mouth during infancy, it becomes difficult for Streptococcus mutans to invade the already balanced oral ecosystem. This significantly reduces the risk of developing caries throughout life from infancy onward. If a person has already been infected with the causative bacteria from an adult's mouth, frequent tooth brushing and maintaining good oral hygiene can help prevent caries. However, once Streptococcus mutans colonizes the oral cavity, it is impossible to eradicate it.

[0057] In one embodiment of the present invention, a disc containing the natural compound of the present invention was inoculated onto a culture medium smeared with Streptococcus mutans, and the size of the growth inhibition zone was then measured. As a result, the diameter of the growth inhibition zone in the experimental group containing the compound was 10.0 mm or more, demonstrating excellent antibacterial activity against Streptococcus mutans. Therefore, it was confirmed that a composition containing the natural compound is useful for preventing or improving dental caries (Table 2).

[0058] In the present invention, "periodontal disease" refers to inflammation of the gums, periodontal ligament, and bone tissue that support the teeth. It is commonly referred to as periodontal disease and can be divided into gingivitis and periodontitis depending on the severity of the disease. Gingivitis is a relatively mild and rapidly reversible form of periodontal disease that is limited to the gums, i.e., soft tissue. Periodontitis is when the inflammation extends to the gums and alveolar bone. There is a V-shaped gap between the gums and teeth. When oral pathogens attack the sulcus below the gum line, lipopolysaccharide (LPS), an inflammatory stimulus, is released, causing inflammation that causes gum swelling and bleeding, and damaging the periodontal ligament and adjacent tissues. Progression of periodontitis can also damage the periodontal ligament and alveolar bone, ultimately resulting in tooth loss. Nutritional deficiencies such as protein and vitamin deficiencies, hormonal disorders due to pregnancy or diabetes, smoking, and acquired immune deficiency syndrome (AIDS) can exacerbate periodontal disease. Other causes of periodontal disease include dental plaque and tartar. The causative bacteria of periodontal disease in the present invention include all bacteria that cause periodontal disease, regardless of type, specifically at least one bacterium selected from the group consisting of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Fusobacterium nucleatum, and more specifically Porphyromonas gingivalis.

[0059] Porphyromonas gingivalis is a Gram-negative anaerobic bacterium related to Bacteroides. It is found in the oral cavity where periodontal disease occurs, as well as in the upper gastrointestinal tract, respiratory tract, and colon. In patients with chronic periodontal disease, the collagenase enzyme produced by this bacterium breaks down collagen. This bacterium invades gingival fibroblasts and can survive even under high concentrations of antibiotics. Furthermore, this bacterium can invade gingival epithelial cells and survive for long periods of time.

[0060] In one embodiment of the present invention, a disc containing the natural compound of the present invention was inoculated onto a medium smeared with Porphyromonas gingivalis, and the size of the growth inhibition zone was then measured. As a result, the diameter of the growth inhibition zone in the experimental group containing the compound was 10.0 mm or more, indicating excellent antibacterial activity against Porphyromonas gingivalis. Therefore, it was confirmed that a composition containing the compound is useful for preventing or improving periodontal disease (Table 2).

[0061] In addition, in one embodiment of the present invention, clinical experiments were conducted on subjects with gingival inflammation. The experimental group that used toothpaste containing the compound showed excellent gingival inflammation inhibitory effects, maintaining normal bleeding even after 6 months and maintaining the gingival inflammation inhibitory effects. Therefore, it was confirmed that compositions containing the natural compounds are useful for preventing or improving periodontal diseases, including gingivitis (Table 4).

[0062] In this specification, "toothache" refers to pain felt in the teeth when eating sweet, very cold, or very hot foods. However, it generally includes pain not only in the tooth itself but also in the periodontal tissues that secure the tooth to the jawbone. Pain usually occurs when chewing, accompanied by swelling of the gums and unpleasant-smelling secretions. Toothache pain varies somewhat depending on the underlying disease. Specifically, in the case of dental caries, pain is absent in the early stages, but pain appears as the condition progresses and reaches the nerve inside the tooth. In the case of an impacted tooth, pain is induced by inflammation of the tissues surrounding the tooth. In the case of a crushed or cracked tooth, pain occurs when the tooth expands upon contact with cold food or when biting hard, irritating the nerve. In the case of pulpitis, pain is felt when touching cold food in the early stages, but pain is felt when touching hot food as the condition progresses. As the inflammation progresses and the pulp tissue necroses, the patient loses sensitivity to cold or hot foods, and pain occurs due to inflammation at the root tip (the tip of the tooth root).

[0063] In one example of the present invention, the inhibitory effect of PGE2, which is known as a pain and inflammation marker, was confirmed, and it was confirmed that the experimental group containing the natural compound of the present invention exhibited a concentration-dependent PGE2 inhibitory effect (Table 5).

[0064] In the present invention, "hypersensitivity" refers to hypersensitive dentin, and hypersensitivity refers to dentin hyperesthesia. Hypersensitivity is a tooth stain that is felt sensitively when exposed dentin is exposed to cold air or spicy foods, and is experienced by 60 to 98% of adults with periodontal disease. Hypersensitivity can be caused by improper toothbrushing habits, excessive biting force, teeth digging into the gums due to acid dissolution, poor oral hygiene, periodontal treatment, restorative treatment, and tooth dissolution due to acidification. The underlying cause of hypersensitivity is the exposure of many tubules present in the dentin of teeth. This exposure directly transmits all stimuli to the nerves in the dental pulp, resulting in a more sensitive response than usual to the same stimuli and pain. Symptoms of tooth sensitivity range from mild to intense, persistent pain, but because teeth do not regenerate, taking painkillers or anti-inflammatory medications is not a fundamental solution to tooth stains. Tooth sensitivity can occur generally over the entire tooth, or it can be limited to specific areas such as the upper or lower jaw, right or left side. The areas where tooth sensitivity occurs most frequently vary depending on the cause, but are primarily canines and premolars, and the area where the most severe pain occurs is the cervical area, the area where the gums meet the teeth, in over 90% of cases.

[0065] In one embodiment of the present invention, clinical experiments were conducted on subjects with hypersensitive dentin. As a result, it was confirmed that the experimental group using toothpaste containing the compound of the present invention had excellent suppression effect on hypersensitivity symptoms, and that compositions containing the natural compounds are useful for preventing or improving hypersensitivity (Table 7).

[0066] In this invention, "bad breath" refers to odors originating from the oral cavity and adjacent organs. 85-90% of bad breath originates in the oral cavity, particularly the posterior part of the tongue. Volatile sulfur compounds are the main components of bad breath, with 90% of the total volatile sulfur compounds being hydrogen sulfide produced from cysteine ​​and methyl mercaptan and dimethyl sulfide produced from methionine. These compounds are primarily produced by protein enzymes secreted by anaerobic bacteria, and the posterior part of the tongue is the most important habitat. This area is difficult to cleanse with saliva and has many small depressions, making it a place where bacteria can continue to live. While the production of volatile sulfur compounds by anaerobic bacteria is the most important cause of bad breath, it can also be caused by other oral diseases such as dental caries, periodontitis, and xerostomia. Various anaerobic bacteria are involved in the generation of bad breath, and examples of bacteria that cause bad breath include, but are not limited to, Porphyromonas gingivalis, which secretes a large amount of various enzymes.

[0067] In one embodiment of the present invention, a clinical experiment was conducted on subjects without dental caries. As a result, it was confirmed that the experimental group using toothpaste containing the natural compound of the present invention had excellent bad breath removal effect, and that compositions containing the compound are useful for preventing or improving bad breath (Table 8).

[0068] The quasi-drug composition of the present invention may include an oral quasi-drug. In addition to the active ingredient, the components contained in the quasi-drug composition of the present invention may include components commonly used in oral quasi-drug compositions as active ingredients, such as abrasives, humectants, binders, foaming agents, sweeteners, preservatives, medicinal ingredients, flavoring agents, pigments, solvents, whitening agents, solubilizers, or pH adjusters.

[0069] The oral quasi-drug composition of the present invention may be prepared in any dosage form commonly used in the art, such as toothpaste, mouthwash, oral cleanser, gum, candy, oral spray, oral ointment, oral varnish, mouthwash, gum massage cream, etc., but is not limited to these.

[0070] For example, when the oral quasi-drug composition of the present invention is in the form of toothpaste, it may contain humectants, abrasives, binders, foaming agents, flavoring agents, sweeteners, coloring agents, preservatives, medicinal ingredients, solvents, pH adjusters, etc.

[0071] The humectant is used to turn the powder in the dentifrice ingredients into a paste and prevent the dentifrice from solidifying in the air. Glycerin, liquid sorbitol, propylene glycol, polyethylene glycol, etc. are used alone or in combination of two or more types to account for 1 to 60% by weight, specifically 10 to 50% by weight, of the total weight of the composition.

[0072] The foaming agent diffuses the dentifrice into the oral cavity to improve the cleaning effect and acts as a surfactant to cleanse oral contaminants. Surfactants such as sodium lauryl sulfate, sodium lauryl sarcosinate, sodium alkylsulfosuccinate, and sucrose fatty acid esters are used alone or in combination of two or more to provide 0.5 to 10% by weight, specifically 0.5 to 5% by weight, of the total weight of the composition.

[0073] The binder prevents separation between the powder and liquid components in the dentifrice, and is used alone or in combination with two or more of cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, and hydroxypropylcellulose, sodium alginate, carrageenan, and xanthan gum, so as to account for 0.1 to 5% by weight, specifically 0.3 to 2% by weight, of the total weight of the composition.

[0074] The abrasive removes deposits from the tooth surface without damaging it, allowing the natural luster of the teeth to emerge. Examples of the abrasive include calcium carbonate (CaCO3), dicalcium phosphate (CaHPO4, CaHPO4·2H2O), anhydrous silicic acid (SiO2·2H2O), aluminum hydroxide (Al(OH)3), potassium pyrophosphate, magnesium carbonate, etc., used alone or in combination of two or more, in an amount of 1 to 60% by weight, specifically 10 to 50% by weight, of the total weight of the composition.

[0075] The flavoring agent is used to add a refreshing feeling and fragrance to the toothpaste and improve the usability, and may be peppermint oil, spearmint oil, menthol, or the like, used alone or in combination of two or more kinds, in an amount of 1 to 60% by weight, specifically 0.01 to 5% by weight, of the total weight of the composition.

[0076] The sweetener is used to remove the unpleasant taste of the toothpaste ingredients and to improve the refreshing feeling, and is used alone or in combination of two or more of saccharinic acid, aspartame, xylitol, glycyrrhizinic acid, etc., in an amount of 1 to 60% by weight, specifically 0.01 to 5% by weight, of the total weight of the composition.

[0077] The active ingredient has effects such as preventing dental caries, periodontal disease, toothache, hypersensitivity, and bad breath, and includes fluoride, zinc chloride, chlorhexidine, aminocaproic acid, tranexamic acid, cetylpyridinium chloride, pyridoxine chloride, triclosan, tocopherol acetate, sodium monofluorophosphate, etc., used alone or in combination of two or more. In the present invention, the above compounds are used as additional active ingredients.

[0078] The oral quasi-drug composition of the present invention can be used alone or in combination, and can also be used in combination with other oral quasi-drug compositions other than those of the present invention.

[0079] Another aspect of the present invention provides a pharmaceutical composition comprising the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient. Specifically, the present invention provides a pharmaceutical composition comprising the natural compound as an active ingredient for preventing or treating at least one oral disease selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, hypersensitivity, and bad breath. The natural compound, oral disease, dental caries, periodontal disease, toothache, hypersensitivity, and bad breath are as described above.

[0080] The pharmaceutical composition of the present invention can be formulated into the form of tablets, pills, powders, granules, capsules, suspensions, oral solutions, emulsions, syrups, aerosols, sterile injection solutions and the like by conventional methods for preventing and treating oral diseases.

[0081] Oral solid preparations include tablets, pills, powders, granules, capsules, etc., and these solid preparations may be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. In addition to the usual excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, oral liquids, emulsions, syrups, etc., and in addition to the commonly used diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, flavorings, preservatives, etc. are used.

[0082] Parenteral preparations include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, etc. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

[0083] The pharmaceutical composition of the present invention may further comprise a carrier, excipient, or diluent, such as lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, or mineral oil such as silicon dioxide.

[0084] The specific dosage of the pharmaceutical composition according to the present invention can be selected by those skilled in the art depending on factors such as the formulation method, the patient's condition, body weight, sex, age, severity of disease, drug form, route and duration of administration, excretion rate, reaction sensitivity, etc., and the dosage and frequency of administration do not limit the present invention in any aspect.

[0085] The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes, including oral, intravenous, intramuscular, or subcutaneous injection.

[0086] Yet another aspect of the present invention provides a food composition comprising the natural compound or a nutrient-acceptable salt thereof as an active ingredient. Specifically, the present invention provides a food composition for preventing or ameliorating at least one oral disease selected from the group consisting of dental caries, periodontal disease (periodontitis or gingivitis), toothache, hypersensitivity, and halitosis, comprising the compound as an active ingredient. The natural compound, oral disease, dental caries, periodontal disease, toothache, hypersensitivity, and halitosis are as described above. The food composition may be used in the form of a functional food, but is not limited thereto.

[0087] The natural compound or its nutritively acceptable salt contained in the food composition of the present invention may be contained in the form of an animal or plant containing the compound, an extract thereof, a fraction thereof, or a processed product thereof. Furthermore, the composition may contain a nutritively acceptable food supplement additive in addition to the active ingredient.

[0088] In the present invention, the term "supplementary food additive" refers to a component added to food as a supplement, which is added when producing functional foods in various dosage forms and can be appropriately selected and used by those skilled in the art. Examples of supplementary food additives include various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers, pectinic acid and its salts, alginic acid and its salts, organic acids, protective colloids, thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonation agents used in carbonated beverages, but the types of supplementary food additives of the present invention are not limited to these examples.

[0089] The food composition of the present invention may include a functional food. In the present invention, the term "functional food" refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc., using raw materials or ingredients that have functional properties beneficial to the human body. Here, "functional" refers to regulating nutrients for the structure and function of the human body or providing beneficial effects for health purposes, such as physiological effects. The functional food of the present invention can be prepared by methods commonly used in the art, and can be prepared by adding raw materials and ingredients commonly added in the art. The dosage form of the functional food is not limited as long as it is recognized as a functional food. The food composition of the present invention can be prepared in various dosage forms. Unlike general medicines, the food composition is made from food ingredients, which has the advantage of being free of side effects that can occur with long-term drug administration. Furthermore, the functional food of the present invention can be taken as an adjuvant for preventing or ameliorating oral diseases.

[0090] The functional food of the present invention may be used in any form, including any food in the conventional sense, and may be used interchangeably with terms known in the art, such as functional health food. Furthermore, the functional food of the present invention can be prepared by mixing other suitable supplementary ingredients or known additives that can be included in foods, as selected by those skilled in the art. Examples of foods to which the functional food of the present invention can be added include meat, sausage, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products such as ice cream, various soups, soft drinks, tea, energy drinks, alcoholic beverages, vitamin complexes, etc. The functional food of the present invention can be prepared by adding the compound of the present invention to soups, teas, jellies, juices, etc., which are made primarily from the compound of the present invention. Foods used as animal feed are also included. [Example]

[0091] The following examples and experimental examples will explain the configuration and effects of the present invention in more detail. These examples and experimental examples are merely illustrative of the present invention, and the present invention is not limited to these examples and experimental examples.

[0092] Experimental Example 1: Antibacterial effect against bacteria that cause dental caries and periodontitis Antibacterial activity experiments were conducted to confirm the preventive or therapeutic effects of compounds of formulas 1 to 15 on dental caries and periodontitis. To confirm the inhibitory effect on the growth of oral pathogenic bacteria, antibacterial activity tests were conducted using a paper disk test method using Streptococcus mutans, a typical bacterium that causes dental caries, and Porphyromonas gingivalis, a typical bacterium that causes periodontal disease.

[0093] The activity of each oral pathogenic bacterium was increased under the optimal culture conditions shown in Table 1, and then cultured in the optimal medium for each bacterium for about 4 to 6 hours until the turbidity of the culture solution reached Macfarland turbidity No. 0.5 (1.5 x 10 8), and 0.1 ml of each oral pathogen was evenly smeared on a plate medium. Then, sterilized paper discs (Whatman No. 5 paper, 8 mm diameter) were inoculated with each of the compounds of formulas 1 to 15 at a concentration of 10 mg / disc and allowed to absorb and dry for 1 hour. Next, each oral pathogen was cultured for 24 to 48 hours at the optimal temperature, after which the size of the growth inhibition zone (diameter in mm) was measured. The results are shown in Table 2.

[0094] [Table 1]

[0095] [Table 2]

[0096] As can be seen from Table 2, compared to the untreated group, the groups treated with the compounds of Chemical Formulas 1 to 15 had growth inhibition zone diameters of 9.5 mm or more against the two oral pathogens, demonstrating excellent antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis. Therefore, it was found that the compounds of Chemical Formulas 1 to 15 are useful for the prevention or treatment of dental caries or periodontal disease.

[0097] Experimental example 2: Inhibitory effect on the onset of gingivitis To confirm the preventive or therapeutic effects of the compounds of Formulas 1 to 15 on gingivitis, a clinical experiment was conducted on a selected experimental group.

[0098] First, a control group toothpaste was prepared using sodium carboxymethylcellulose, sodium lauryl sulfate, glycerin, colloidal silicon dioxide, silicas, sodium cocoyl isethionate, dosing, sweeteners, flavoring agents, coloring agents, etc., which are commonly used in manufacturing toothpaste. Then, 0.01 wt % of any of the compounds of Chemical Formulas 1 to 15 was added to the control group toothpaste to prepare an experimental group toothpaste.

[0099] To select the test subjects, gingival inflammation patients with well-aligned teeth and no missing teeth were selected. Thirty men and women, aged between 30 and 50, were selected in 10-year increments and given detailed oral examinations. A group of 120 people was then selected and divided into groups of 60 people each. Clinical experiments on the therapeutic effects of gingival inflammation were conducted as follows.

[0100] Specifically, the experimental group was divided into a control group and an experimental group. The control group was instructed to use the control toothpaste three times a day, two hours after meals, while the experimental group was instructed to use the experimental toothpaste three times a day at the same time as the control group. Afterward, subjects were given oral hygiene and scored for the initial gingivitis index. The control group used the control toothpaste, and the experimental group used the experimental toothpaste. Oral examinations were conducted one week, one month, three months, and six months later to assess the gingivitis index. The gingivitis index was measured by inserting a periodontal probe into the gingival sulcus and gently probing around each tooth. After 30 seconds, bleeding was measured and scored according to the criteria shown in Table 3. The results are shown in Table 4.

[0101] [Table 3]

[0102] [Table 4]

[0103] As can be seen from Table 4, compared to the control group, the experimental group using toothpaste containing any of the compounds of Chemical Formulas 1 to 15 maintained normal bleeding even after 6 months, demonstrating that the gingival inflammation inhibitory effect was sustained. Therefore, it was found that the compounds of Chemical Formulas 1 to 15 are useful for preventing or treating gingivitis.

[0104] Experimental Example 3: Inhibitory effect of PGE2, a pain and inflammation marker To confirm the preventive or therapeutic effect of the compounds of Chemical Formulas 1 to 15 on toothache, the inhibitory effect of PGE2, known as a pain and inflammation marker, was examined.

[0105] First, 1.5 × 10 macrophages were cultured in DMEM medium containing 10% FBS. 5 The cells were seeded at a concentration of 1000 cells / ml and cultured in a 24-well plate at 37°C and 5% CO2 for 24 hours. Next, the cells were treated with 1 μg / ml of LPS, an inflammation-inducing stimulus, and various concentrations of the compounds of formulas 1 to 15, and cultured for an additional 24 hours. The PGE2 inhibitory activity of the supernatants at various concentrations of the compounds of formulas 1 to 15 was then analyzed using a PGE2 ELISA assay kit (Thermo Scientific) (Table 5).

[0106] [Table 5]

[0107] As can be seen from Table 5, compared to the group treated with LPS only, all of the compounds of chemical formulas 1 to 15 were confirmed to exhibit a concentration-dependent PGE2 inhibitory effect, and were confirmed to have excellent preventive and therapeutic effects on toothache.

[0108] Experimental Example 4: Hypersensitivity suppression effect Clinical trials were conducted on selected subjects to confirm the preventive or therapeutic effects of the compounds of Chemical Formulas 1 to 15 on tooth sensitivity. The control toothpaste and experimental toothpaste used in the clinical trials were prepared in the same manner as the toothpaste in Experimental Example 2.

[0109] The subjects were 40 volunteers with sensitive dentin who agreed to participate in the study. A total of 80 teeth were tested. 20 were male and 20 were female, ranging in age from 20 to 50 years old. The subjects were blinded to the contents of the toothpaste, and the entire study lasted for two weeks.

[0110] The experiment involved applying temperature stimuli and measuring the subjects' reactions. Prior to the experiment, each subject's dentin was checked for hypersensitivity. Cold water (approximately 5°C) was dripped onto the sensitive area with a dropper and scored according to the criteria shown in Table 6. The control group was then instructed to use the control toothpaste, and the experimental group was instructed to use the experimental toothpaste three times a day for two weeks. After two weeks, cold water (approximately 5°C) was dripped onto the sensitive area with a dropper and scored again. Statistical analysis was performed using a paired Student's t-test to assess the stimuli scores before and after the experiment. The response scores to the temperature stimuli two weeks later are shown in Table 7.

[0111] [Table 6]

[0112] [Table 7]

[0113] As can be seen from Table 7, compared to the control group, the experimental group using toothpaste containing each compound of Chemical Formulas 1 to 15 showed suppressed hypersensitivity after 2 weeks. Therefore, it was found that the compounds of Chemical Formulas 1 to 15 are useful for preventing or treating hypersensitivity.

[0114] Experimental example 5: Bad breath removal effect Clinical trials were conducted on selected test subjects to confirm the preventive or therapeutic effects of the compounds of Chemical Formulas 1 to 15 on bad breath. The control toothpaste and experimental toothpaste used in the clinical trials were prepared in the same manner as the toothpaste in Experimental Example 2.

[0115] Fifty caries-free men and women were selected as subjects, and a cross-over test was conducted using the control and experimental toothpastes. Commercially available garlic powder was dispersed in water and left for 24 hours. It was then diluted to a Halimeter reading of 700 ppb or higher, and the diluted solution was used as a halitosis inducer. Subjects were instructed to gargle with 15 ml of the diluted garlic powder for 30 seconds, and the level of halitosis was measured with the Halimeter one minute later. After that, the control group used the control toothpaste, and the experimental group used the experimental toothpaste, and they brushed their teeth for 30 seconds to one minute. The level of halitosis was measured with the Halimeter one minute, five minutes, and 30 minutes after brushing to determine whether halitosis suppression persisted. The results are shown in Table 8.

[0116] [Table 8]

[0117] As can be seen from Table 8, compared to the control group, the experimental group using toothpaste containing each compound of Chemical Formulas 1 to 15 had about 95% or more of bad breath removed 1 minute after brushing, and even 30 minutes after brushing, the bad breath removal rate was still 80% or more, showing a much better bad breath removal effect. Therefore, it was found that the compounds of Chemical Formulas 1 to 15 are useful for preventing or treating bad breath.

Claims

1. A quasi-drug composition for preventing or improving oral diseases, comprising sclareolide or a pharmaceutically acceptable salt thereof as an active ingredient, the oral disease is toothache or tooth sensitivity; A quasi-drug composition, wherein the sclareolide or a pharmaceutically acceptable salt thereof is an active ingredient that suppresses the pain marker PEG2 to improve toothache, or an active ingredient that suppresses the symptoms of hypersensitivity in teeth with dentin hypersensitivity to improve hypersensitivity.

2. The quasi-drug is for oral use, The quasi-drug composition according to claim 1, wherein the dosage form of the quasi-drug composition is at least one selected from the group consisting of toothpaste, mouthwash, oral cleanser, gum, candy, oral spray, oral ointment, oral varnish, mouthwash, and gum massage cream.

3. A pharmaceutical composition for preventing or treating an oral disease, comprising sclareolide or a pharmaceutically acceptable salt thereof as an active ingredient, the oral disease is toothache or tooth sensitivity; A pharmaceutical composition, wherein the sclareolide or a pharmaceutically acceptable salt thereof is an active ingredient that suppresses the pain marker PEG2 to improve toothache, or an active ingredient that suppresses the symptoms of hypersensitivity in teeth with dentin hypersensitivity to improve hypersensitivity.

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