Hydrangea extract and composition containing same as active ingredient for preventing, alleviating, or treating periodontitis

Abstract

The present invention discloses a composition containing a hydrangea extract, Thunberginol C, hydrangeic acid, hydrangenol, or a sitologically acceptable salt thereof as an active ingredient for preventing, alleviating, or treating periodontitis. The present invention has the effect of preventing, alleviating, or treating periodontitis by inhibiting inflammation, protecting periodontal tissue, and alleviating bone loss through inhibition against the production of TNF-alpha mRNA, IL-6 mRNA, MMP-3 mRNA, MMP-9 mRNA, MMP-13 mRNA, and PGE2 and the expression of COX-2 mRNA and through an increase in BMD and a decrease in CEJ-ABC, thereby protecting periodontal tissue.

Description

Hydrangea extract and composition for the prevention, improvement, or treatment of periodontitis of its active ingredients

[0001] The present invention relates to a composition for the prevention, improvement, or treatment of periodontitis.

[0002]

[0003] The gums are a layer of protective tissue that covers a portion of the jawbone surrounding the underside of each tooth. Healthy gums tightly seal the area around the tooth crown, protecting the tissue from bacterial invasion. Most adults have some degree of gum disease, but if left untreated, it can lead to tooth loss. If teeth are not brushed properly, plaque accumulates on the tooth surface; if this plaque is not removed, it causes inflammation of the gums.

[0004] Gum inflammation, known as gum disease, is an inflammation of the gums caused by poor oral hygiene and is a very common condition affecting 9 out of 10 adults. Instead of the normal pink color, the gums appear purplish, soft, and shiny, and bleed easily, especially when brushing. This condition usually occurs due to the accumulation of plaque where the gums meet the underside of the teeth. When gum inflammation develops suddenly, it is called acute necrotizing ulcerative gingivitis, and it typically affects teenagers and young adults. The cause is sometimes chronic gingivitis or the abnormal growth of harmless bacteria in the mouth.

[0005] If gingivitis progresses, it develops into periodontitis. It primarily affects people over the age of 55 and is one of the main causes of tooth loss. Inflammation occurs in the periodontal tissues that anchor the teeth to the alveolar sockets, causing the teeth to loosen and eventually fall out. If periodontitis is left untreated, it increases the risk of cardiovascular disease.

[0006] Periodontal disease is an inflammatory disease of periodontal tissues caused by microorganisms in dental plaque, characterized by the destruction of surrounding tissues and loss of attachment. The balance between periodontal destruction and stability is determined by various factors, among which periodontal destruction occurs when the production of inflammatory cytokines, matrix metalloproteinases (MMPs), and prostaglandin E2 (PGE2) increases. In this case, PGE2 levels can be regulated by the upstream enzyme, cyclooxygenase-2 (COX-2).

[0007] When periodontal disease occurs, damage to the tooth-supporting structures leads to changes in bone density and structure. When periodontitis is induced, inflammation promotes bone resorption, resulting in a decrease in Bone Mineral Density (BMD) and an increase in Cementum-Enamel Junction to Alveolar Bone Crest (CEJ-ABC).

[0008] Plant-derived materials have long been used due to their superior safety, and in Korea, in particular, the development of functional materials primarily based on plants and medicinal ingredients used in the private sector or traditional Korean medicine is actively underway.

[0009] However, the use of hydrangea extract and its active ingredients for the prevention, improvement, or treatment of periodontitis is unknown, and research on their mechanisms has not been conducted. Therefore, the inventors conducted a study on the direct efficacy of hydrangea extract and its active ingredients for the prevention, improvement, or treatment of periodontitis.

[0010] Accordingly, the inventors of the present invention have made efforts to develop a composition for preventing, improving, or treating periodontitis, and have confirmed that hydrangea extract and its active ingredients can prevent, improve, or treat periodontitis, thereby completing the present invention.

[0011]

[0012] One aspect provides a health functional food composition for preventing or improving periodontitis comprising, as an active ingredient, a hydrangea extract; or Thunberginol C represented by the following chemical formula 1; or hydrangic acid represented by chemical formula 2; or hydrangenol represented by chemical formula 3; or a food-grade acceptable salt thereof.

[0013] [Chemical Formula 1]

[0014]

[0015] [Chemical Formula 2]

[0016]

[0017] [Chemical Formula 3]

[0018]

[0019] Another aspect provides a pharmaceutical composition for the prevention or treatment of periodontitis comprising, as an active ingredient, a hydrangea extract; or Thunberginol C represented by Chemical Formula 1; or Hydrangeic acid represented by Chemical Formula 2; or Hydrangenol represented by Chemical Formula 3; or a food-grade acceptable salt thereof.

[0020] Another aspect provides a quasi-drug composition for the prevention or improvement of periodontitis comprising, as an active ingredient, a hydrangea extract; or Thunberginol C represented by the following chemical formula 1; or hydrangic acid represented by chemical formula 2; or hydrangenol represented by chemical formula 3; or a food-grade acceptable salt thereof.

[0021] Another aspect provides a topical skin composition for preventing or improving periodontitis comprising, as an active ingredient, a hydrangea extract; or Thunberginol C represented by Chemical Formula 1; or Hydrangeic acid represented by Chemical Formula 2; or Hydrangenol represented by Chemical Formula 3; or a food-grade acceptable salt thereof.

[0022] Another aspect provides a method for preventing, improving, or treating periodontitis comprising the step of administering an active ingredient to an individual in need of it, the active ingredient being a hydrangea extract; or Thunberginol C represented by Chemical Formula 1; or Hydrangeic acid represented by Chemical Formula 2; or Hydrangenol represented by Chemical Formula 3; or a food-grade acceptable salt thereof.

[0023] Another aspect provides a use for hydrangea extract; or Thunberginol C represented by Chemical Formula 1; or Hydrangeic acid represented by Chemical Formula 2; or Hydrangenol represented by Chemical Formula 3; or a food-grade acceptable salt thereof as an active ingredient in the preparation of a composition for the prevention, improvement, or treatment of periodontitis.

[0024]

[0025] One aspect provides a health functional food composition for preventing or improving periodontitis comprising, as an active ingredient, a hydrangea extract; or Thunberginol C represented by the following chemical formula 1; or hydrangic acid represented by the following chemical formula 2; or hydrangenol represented by the following chemical formula 3; or a food-grade acceptable salt thereof.

[0026] [Chemical Formula 1]

[0027]

[0028] [Chemical Formula 2]

[0029]

[0030] [Chemical Formula 3]

[0031]

[0032] A health functional food composition for preventing or improving periodontitis may include an active ingredient comprising at least one of the hydrangea extract, Thunberginol C represented by Chemical Formula 1, Hydrangeic acid represented by Chemical Formula 2, Hydrangenol represented by Chemical Formula 3, and a food-grade acceptable salt thereof.

[0033] It can be used by isolating and purifying from natural products of the genus Hydrangea of ​​the family Hydrangea. The genus Hydrangea may be one or more selected from the group consisting of the whole, woody roots, stems, branches, leaves, seeds, or fruits, and preferably, leaves may be used.

[0034] The above-mentioned hydrangea is a perennial plant of the Asteraceae family and may be a plant whose leaves are specified as an edible part in the food ingredient list notified by the Ministry of Food and Drug Safety.

[0035] According to the example, the hydrangea extract may be a wild hydrangea extract. Wild hydrangea (Hydrangea serrata) is a broad-leaved small tree of the Saxifragaceae family, and its leaves are listed as an edible part in the food ingredients notified by the Ministry of Food and Drug Safety. Wild hydrangea (Hydrangea serrata (Thunb.) Ser.) is native to Korea, and its leaves are used to make traditional Korean tea.

[0036] The above-mentioned hydrangea extract may be an extract obtained by solvent from the whole, part thereof, or material derived therefrom of the above-ground parts of the tree. The part thereof may be the stem, root, leaf, flower, petal, seed, pulp, fruit peel, or fruit of the tree, and preferably may be the leaf. The whole, part thereof, or material derived therefrom of the tree used for extraction may be ground or chopped, or suitably dried.

[0037] The above hydrangea extract can be extracted by any extraction method conventionally used to extract natural plants, such as hot water extraction, solvent extraction, distillation extraction, or supercritical extraction, and is preferably characterized by being extracted with water, an organic solvent, or a mixture of solvents thereof. The above organic solvent may be one or more selected from the group consisting of alcohols having 1 to 4 carbon atoms, such as ethanol, methanol, isopropanol, and butanol. In addition, the above alcohol may include ethanol. The alcohol concentration of the above aqueous alcohol solution may be 1 to 99.5 (v / v)%, for example, 10 to 99.5 (v / v)%, 1 to 70 (v / v)%, 1 to 40 (v / v)%, 5 to 50 (v / v)%, 5 to 40 (v / v)%, 10 to 50 (v / v)%, or 10 to 40 (v / v)%.

[0038] The above extraction may include adding the above extraction solvent to the hydrangea in an amount of 3 to 50 (w / w), for example, 3 to 40 (w / w), 3 to 30 (w / w), 5 to 50 (w / w), 5 to 40 (w / w), 5 to 30 (w / w), or 4 to 40 (w / w). For example, it may include adding 3 to 50 kg of the above extraction solvent per 1 kg of material derived from the hydrangea.

[0039] The above extraction may utilize methods such as hot water extraction, immersion extraction, supercritical extraction, subcritical extraction, reflux cooling extraction, steam distillation, high-pressure enzymatic hydrolysis, ultrasonic extraction, elution, and pressing.

[0040] The above extraction may be performed at 4°C to 90°C, for example, 4°C to 80°C, 4°C to 70°C, 5°C to 80°C, 10°C to 70°C, 15°C to 70°C, or 20°C to 70°C. The above extraction time may vary depending on the selected temperature and may be 1 hour to 2 months, for example, 1 hour to 1 month, 1 hour to 10 days, 1 hour to 5 days, 1 hour to 3 days, 1 hour to 2 days, 1 hour to 1 day, 1 hour to 10 hours, 2 hours to 1 month, 2 hours to 15 days, 2 hours to 10 days, 2 hours to 5 days, 2 hours to 3 days, 2 hours to 2 days, 2 hours to 1 day, or 2 hours to 10 hours. The above extraction may include mixing the whole hydrangea, a part thereof, or a material derived therefrom in the above solvent and leaving it for a certain period of time. The leaving it may include appropriate stirring. The above extraction may be repeated one or more times, for example, 1 to 5 times.

[0041] The above extraction may separate the plant residue and the extract by known methods such as filtration. The above extraction may also include removing the solvent from the obtained extract by known methods such as reduced pressure concentration. The above extraction may also include preparing a dried extract by drying the obtained extract, such as freeze-drying.

[0042] The active ingredients Thunberginol C, hydrrangeic acid, and hydrrangenol may be isolated from a hydrangea extract, and specifically, may be fractions of the hydrangea extract. The fraction refers to a substance containing a specific component isolated from the extract. The Thunberginol C, hydrrangeic acid, and hydrrangenol may be separated and purified using column chromatography. The above chromatography may be selected from silica gel column chromatography, HP-20 column chromatography, RP-18 column chromatography, LH-20 column chromatography, high-performance liquid chromatography, or a combination thereof.

[0043] In one embodiment, the hydrangea extract, the Thunberginol C, the hydrangic acid, or the hydrangenol is present in an amount of 0.0001 wt% to 90.0 wt% based on the total weight of the composition, for example, 0.01 wt% to 60 wt%, 0.01 wt% to 40 wt%, 0.01 wt% to 30 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt%, 0.05 wt% to 60 wt%, 0.05 wt% to 40 wt%, 0.05 wt% to 30 wt%, 0.05 wt% to 20 wt%, 0.05 wt% to 10 wt%, 0.05 wt% to 5 wt%. It may be included in an amount of 0.1 wt% to 60 wt%, 0.1 wt% to 40 wt%, 0.1 wt% to 30 wt%, 0.1 wt% to 20 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 5 wt%, 5 to 20 wt%, 5 to 18 wt%, 6 to 15 wt%, 8 to 15 wt%, or 7 to 10 wt%. However, in the case of long-term consumption for the purpose of health and hygiene or health control, it may be below the above range, and since there is no problem in terms of safety, the active ingredient may also be used in an amount greater than the above range.

[0044] The above hydrangea extract, Thunberginol C, hydrangic acid, or hydrangenol may be added as is or used together with other foods or food ingredients, and may be used appropriately according to conventional methods.

[0045] In one embodiment, the hydrangea extract may inhibit the expression of TNF-α (Tumor necrosis factor-alpha) mRNA.

[0046] In one embodiment, the hydrangea extract may inhibit the expression of IL-6 (Interleukin-6) mRNA.

[0047] In one embodiment, the hydrangea extract may inhibit the expression of MMP-3 (matrix metalloproteinases 3) mRNA.

[0048] In one embodiment, the hydrangea extract may inhibit the expression of MMP-9 (matrix metalloproteinases 9) mRNA.

[0049] In one embodiment, the hydrangea extract may inhibit the expression of MMP-13 (matrix metalloproteinases 13) mRNA.

[0050] In one embodiment, the hydrangea extract may inhibit the production of PGE2 (prostaglandin E2).

[0051] In one embodiment, the hydrangea extract may inhibit the expression of COX-2 (cyclooxygenase-2) mRNA.

[0052] In one embodiment, the hydrangea extract may increase bone mineral density (BMD).

[0053] In one embodiment, the hydrangea extract may reduce CEJ-ABC (Cementum-Enamel Junction to Alveolar Bone Crest).

[0054] In one specific example, Thunberginol C may inhibit the production of PGE2 (prostaglandin E2).

[0055] In one embodiment, hydrangic acid may inhibit the production of PGE2 (prostaglandin E2).

[0056] In one embodiment, hydrangenol may inhibit the production of PGE2 (prostaglandin E2).

[0057] The above hydrangea extract may prevent, improve, or treat periodontitis by inhibiting inflammation, protecting periodontal tissues, and alleviating bone loss through the production of inflammatory mediators such as TNF-α (Tumor necrosis factor-alpha) mRNA, IL-6 (Interleukin-6) mRNA, PGE2 (prostaglandin E2), and COX-2 (cyclooxygenase-2) mRNA, as well as enzymes that destroy gum components such as MMP-3 (matrix metalloproteinases 3) mRNA, MMP-9 (matrix metalloproteinases 9) mRNA, and MMP-13 (matrix metalloproteinases 13) mRNA, and by increasing BMD (Bone Mineral Density) and decreasing CEJ-ABC (Cementum-Enamel Junction to Alveolar Bone Crest).

[0058] Thunberginol C, hydrrangeic acid, or hydrrangenol, which are active ingredients of the above extract, may prevent, improve, or treat periodontitis by inhibiting the production of PGE2 (prostaglandin E2).

[0059] In this specification, the term "prevention" collectively refers to partially or completely delaying or preventing the onset or recurrence of a disease, disorder, or its associated symptoms, preventing the acquisition or reacquisition of a disease or disorder, or reducing the risk of acquiring a disease or disorder. Such prevention refers to any act of suppressing or delaying the occurrence of periodontitis or periodontitis-related diseases, disorders, or symptoms through the administration of a composition according to the present invention.

[0060] In this specification, the term "improvement" refers to any action that at least reduces parameters related to the condition being treated, such as the degree of symptoms.

[0061] In this specification, the term "treatment" refers to any act that improves or beneficially alters a disease, disorder, or its associated symptoms.

[0062] In this specification, the term "health functional food" refers to a food manufactured or processed for the purpose of health supplementation using specific ingredients as raw materials or by methods such as extraction, concentration, purification, or mixing of specific ingredients contained in food raw materials, and refers to a food designed and processed to fully exert bio-regulatory functions on the body, such as biological defense, regulation of biological rhythms, and prevention and recovery from disease, through said ingredients. The above-mentioned health functional food composition can perform functions related to the prevention and improvement of periodontitis, etc.

[0063] There are no specific restrictions on the types of the above-mentioned foods. Examples of foods to which the above-mentioned extract may be added include formulations selected from the group consisting of powders, granules, tablets, capsules, pills, gels, jellies, suspensions, emulsions, syrups, tea bags, infusions, gum, candies, and health drinks, and include all health foods in the conventional sense.

[0064] The above health drink composition may include various sweeteners, flavorings, or natural carbohydrates as additional ingredients, as in ordinary beverages. The sweetener may be a natural sweetener or a synthetic sweetener. The natural sweetener may be taumatin or stevia extract, and the synthetic sweetener may be saccharin or aspartame.

[0065] The above natural carbohydrate may be monosaccharide, disaccharide, polysaccharide, xylitol, sorbitol, or erythritol. The above monosaccharide may be glucose or fructose, and the disaccharide may be maltose or sucrose. The polysaccharide may be dextrin or cyclodextrin. The proportion of the above natural carbohydrate may generally be about 0.01 to 10 g, for example, about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

[0066] The above-mentioned health functional food may include food-grade acceptable food additives and may include a suitable carrier commonly used in the manufacture of health functional foods.

[0067] In addition to the above, the composition of the present invention may include various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. Furthermore, the composition of the present invention may include fruit pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages. These ingredients may be used independently or in combination. Although the proportion of these additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

[0068] Another aspect provides a pharmaceutical composition for the prevention or treatment of periodontitis comprising, as an active ingredient, hydrangea extract, Thunberginol C, hydrangic acid, hydrangenol, or a food-grade acceptable salt thereof.

[0069] A pharmaceutical composition for preventing or improving periodontitis may include an active ingredient comprising at least one of the hydrangea extract, Thunberginol C represented by Chemical Formula 1, Hydrangeic acid represented by Chemical Formula 2, Hydrangenol represented by Chemical Formula 3, and a food-grade acceptable salt thereof.

[0070] The effects of the above-mentioned hydrangea extract, Thunberginol C, hydrangic acid, hydrangenol, or a food-grade salt thereof on periodontitis are as described above.

[0071] Another aspect provides a method for preventing, improving, or treating periodontitis comprising the step of administering a hydrangea extract, Thunberginol C, hydrangic acid, hydrangenol, or a food-grade acceptable salt thereof to an individual in need thereof.

[0072] Another aspect provides a use for hydrangea extract, Thunberginol C, hydrangic acid, hydrangenol, or a food-grade salt thereof in the preparation of a composition for the prevention, improvement, or treatment of periodontitis.

[0073] In one embodiment, the pharmaceutical composition may be formulated into a preparation selected from the group consisting of tablets, soft or hard capsules, pills, powders, suspensions, syrups, injections, and granules.

[0074] In one embodiment, the pharmaceutical composition may be for oral or parenteral administration.

[0075] The above pharmaceutical composition may include conventional fillers, extenders, binders, disintegrants, anticoagulants, lubricants, wetting agents, pH adjusters, nutrients, vitamins, electrolytes, alginic acid and its salts, pectic acid and its salts, protective colloids, glycerin, flavorings, emulsifiers, or preservatives.

[0076] The above pharmaceutical composition may include a pharmaceutically acceptable carrier, examples of which may be one or more selected from the group consisting of lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin and physiological saline.

[0077] The formulation of the above pharmaceutical composition may vary depending on the method of use and may be formulated using methods well known in the art to which the present invention belongs so as to provide rapid, sustained, or delayed release of the active ingredient after administration to mammals.

[0078] Preparations for oral administration include tablets, soft or hard capsules, pills, powders, suspensions, syrups, injections, and granules, and these preparations may be prepared by mixing one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients. Preparations for parenteral administration may be creams, lotions, ointments, ointments, liquids, aerosols, fluid extracts, elixirs, infusions, sachets, patches, or injections.

[0079] The above method is applicable to any animal, and the animal may include humans and primates, as well as livestock such as cattle, pigs, sheep, horses, dogs, and cats.

[0080] The dosage of the above composition for treatment, prevention, or improvement can be determined by considering the method of administration, the age and gender of the user, the severity and condition of the patient, the absorption and inactivation rate of the active ingredient in the body, and concomitant drugs, and may be administered as 0.1 mg / kg (body weight) to 500 mg / kg (body weight), 0.1 mg / kg (body weight) to 400 mg / kg (body weight), or 1 mg / kg (body weight) to 300 mg / kg (body weight) based on the daily active ingredient, and may be administered once or in multiple doses, but is not limited thereto.

[0081] Another aspect provides a quasi-drug composition for preventing or improving periodontitis comprising hydrangea extract, Thunberginol C, hydrangic acid, hydrangenol, or a food-grade acceptable salt thereof as an active ingredient.

[0082] A quasi-drug composition for preventing or improving periodontitis may include an active ingredient comprising at least one of the hydrangea extract, Thunberginol C represented by Chemical Formula 1, Hydrangeic acid represented by Chemical Formula 2, Hydrangenol represented by Chemical Formula 3, and a food-grade acceptable salt thereof.

[0083] The effects of the above-mentioned hydrangea extract, Thunberginol C, hydrangic acid, hydrangenol, or food-grade acceptable salts thereof on periodontitis are as described above.

[0084] The term "quasi-drug" refers to articles falling under one of the following categories: fibers, rubber products, or similar items used for the purpose of treating, alleviating, managing, or preventing diseases in humans or animals; items similar thereto that have a weak effect on the human body or do not act directly on the human body and are not instruments or machines; and preparations used for sterilization, insecticidal, and similar purposes for the prevention of infection; excluding articles used for the purpose of diagnosing, treating, alleviating, managing, or preventing conditions or diseases in humans or animals that are not instruments, machines, or devices, and articles used for the purpose of exerting pharmacological effects on the structure and function of humans or animals that are not instruments, machines, or devices; and may also include personal hygiene products.

[0085] When adding hydrangea extract, Thunberginol C, hydrangic acid, hydrangenol, or a food-grade salt thereof to a quasi-drug composition, the extract may be added as is or used in combination with other quasi-drug ingredients, or may be used appropriately according to conventional methods. The amount of the active ingredients may be appropriately determined according to the purpose of use (prevention, health, or therapeutic treatment).

[0086] The type or formulation of the quasi-drug composition of the present invention is not particularly limited, but may be a bandage, gauze, absorbent cotton, adhesive bandage, disinfectant cleaner, shower foam, mouthwash, wet wipe, detergent soap, hand wash, humidifier filler, mask, or filter filler.

[0087]

[0088] Another aspect provides a topical skin composition for preventing or improving periodontitis comprising hydrangea extract, Thunberginol C, hydrangic acid, hydrangenol, or a food-grade acceptable salt thereof as an active ingredient.

[0089] A skin external preparation composition for preventing or improving periodontitis may include an active ingredient comprising at least one of the hydrangea extract, Thunberginol C represented by Chemical Formula 1, Hydrangeic acid represented by Chemical Formula 2, Hydrangenol represented by Chemical Formula 3, and a food-grade acceptable salt thereof.

[0090] The above-mentioned topical agent may be an oral topical agent.

[0091] The effects of hydrangea extract, Thunberginol C, hydrangic acid, hydrangenol, or food-grade salts thereof on periodontitis are as described above.

[0092] The above-mentioned topical skin preparation may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal patch, lotion, or a combination thereof. The above-mentioned topical skin preparation may be appropriately formulated as needed with ingredients commonly used in topical skin preparations such as cosmetics or pharmaceuticals, for example, aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizers, thickeners, UV absorbers, whitening agents, preservatives, antioxidants, surfactants, fragrances, colorants, various skin nutrients, or combinations thereof. The above external skin preparation may also appropriately incorporate metal chelating agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid; caffeine, tannin, bellapamil, licorice extract, glablidin, hot water extract of the fruit of *Calin*; various herbal medicines; preparations such as tocopherol acetate, glycyrrhizic acid, tranexamic acid and its derivatives or salts; and sugars such as vitamin C, magnesium ascorbate phosphate, ascorbate glucoside, arbutin, kojic acid, glucose, fructose, and trehalose.

[0093] When an active ingredient comprising the above-mentioned hydrangea extract, Thunberginol C, hydrrangeic acid, hydrangenol, or a food-grade salt thereof is added to a topical composition, the above-mentioned hydrangea extract, Thunberginol C, hydrrangeic acid, hydrangenol, or a food-grade salt thereof may be added as is or used in combination with other topical ingredients, and may be used appropriately according to conventional methods. The amount of the mixture of active ingredients may be appropriately determined according to the purpose of use (prevention, health, or therapeutic treatment).

[0094] The above skin includes all skin parts of the body, including the face, hands, arms, legs, feet, chest, abdomen, back, buttocks, and scalp.

[0095]

[0096] A composition according to one aspect inhibits the expression of TNF-α mRNA, IL-6 mRNA, MMP-3 mRNA, MMP-9 mRNA, MMP-13 mRNA, PGE2 production, and COX-2 mRNA, and has the effect of preventing, improving, or treating periodontitis by inhibiting inflammation, protecting periodontal tissues, and alleviating bone loss through an increase in BMD and a decrease in CEJ-ABC.

[0097]

[0098] Figure 1 is a graph showing the expression level of IL-1β-induced TNF-α mRNA according to treatment with hydrangea extract.

[0099] Figure 2 is a graph showing the expression level of IL-6 mRNA induced by IL-1β following treatment with hydrangea extract.

[0100] Figure 3 is a graph showing the expression level of IL-1β-induced MMP-3 mRNA according to treatment with hydrangea extract.

[0101] Figure 4 is a graph showing the expression level of IL-1β-induced MMP-9 mRNA following treatment with hydrangea extract.

[0102] Figure 5 is a graph showing the expression level of IL-1β-induced MMP-13 mRNA according to treatment with hydrangea extract.

[0103] Figure 6 is a graph showing the amount of PGE2 produced by IL-1β following treatment with hydrangea extract.

[0104] Figure 7 is a graph showing the expression levels of IL-1β-induced COX-2 mRNA following treatment with hydrangea extract.

[0105] Figure 8 is a graph showing the 3D-micro-CT results in a ligation-induced periodontitis model treated with hydrangea extract.

[0106] Figure 9 is a graph showing the amount of PGE2 produced in IL-1β following Thunberginol C treatment.

[0107] Figure 10 is a graph showing the amount of PGE2 produced in IL-1β following treatment with hydrangic acid.

[0108] Figure 11 is a graph showing the amount of PGE2 produced in IL-1β following treatment with hydrangenol.

[0109]

[0110] The following examples will be explained in more detail. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

[0111] The terms used in this specification are for describing embodiments and are not intended to limit the invention. In this specification, the singular form includes the plural form unless specifically stated otherwise in the text. The terms "comprises" and / or "comprising" used in this specification do not exclude the presence or addition of one or more other components, steps, actions, and / or elements to the mentioned components, steps, actions, and / or elements.

[0112] As used herein, terms such as “examples,” “examples,” “aspects,” “examples,” etc., are not to be interpreted as implying that any described aspect or design is superior or advantageous to other aspects or designs.

[0113] Also, the term "or" means an inclusive or rather an exclusive or. That is, unless otherwise noted or is clear from the context, the expression "x uses a or b" means any one of the natural inclusive permutations.

[0114] Additionally, singular expressions (“a” or “an”) used in this specification and claims should generally be interpreted to mean “one or more” unless otherwise stated or it is clear from the context that they relate to the singular form.

[0115] In addition, when it is said that a part such as a membrane, layer, region, or configuration request is "on" or "on" another part, it includes not only cases where it is directly on top of the other part, but also cases where another membrane, layer, region, or component is interposed in between.

[0116]

[0117] Example 1. Preparation of Hydrangea (Hydrangea serrata Seringe) Extract

[0118] Dried hydrangea leaves (Hydrangea serrata (Thunb.) Ser.) were purchased from Boseong Special Agricultural Products. 1,500 kg of purified water, equivalent to 15 to 20 times the volume of 100 kg of dried hydrangea leaves, was added and refluxed at 98°C for 5 hours, after which the extract was obtained through vacuum filtration (cartridge cylindrical filter 10–50 μm). The extract was concentrated by vacuum concentration at 60°C to obtain a concentrate, and subsequently, a hydrangea extract was obtained through spray drying under conditions of an inlet temperature of 180–200°C and an outlet temperature of 80–100°C (yield 23%).

[0119]

[0120] Experimental Example 1. Confirmation of the inhibitory effect of Hydrangea serrata extract and IL-1β (Interleukin-1β) on TNF-α mRNA expression

[0121] To confirm the inhibitory effect of the hydrangea extract of Example 1 on TNF-α mRNA expression, TNF-α mRNA expression was checked after inducing an inflammatory response with IL-1β.

[0122] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a ratio of 2.0 x 10 5After attaching cells at a concentration of 3 ml / well for 24 hours, the hydrangea extract of Example 1 was treated to FM at concentrations of 12.5, 25, and 50 μg / ml, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 20 hours, mRNA was extracted from the cells and synthesized into cDNA. Quantitative real-time PCR was performed using target primers to finally evaluate the level of TNF-α gene expression, and the results are shown in Figure 1.

[0123]

[0124] Figure 1 is a graph showing the expression level of TNF-α mRNA derived from IL-1β (Interleukin-1β) following treatment with hydrangea extract.

[0125] As shown in Figure 1, it was confirmed that the extract of *Hydrangea serrata* significantly inhibits the expression of TNF-α mRNA.

[0126] The above results indicate that the hydrangea serrata extract according to one embodiment effectively inhibits TNF-α mRNA expression, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0127]

[0128] Experimental Example 2. Confirmation of the inhibitory effect of Hydrangea serrata extract and IL-6 mRNA expression derived from IL-1β (Interleukin-1β)

[0129] To confirm the inhibitory effect of the hydrangea extract of Example 1 on IL-6 mRNA expression, IL-6 mRNA expression was checked after inducing an inflammatory response with IL-1β.

[0130] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a height of 2.0 x 10 5 After attaching to cells at a concentration of 3 ml / well for 24 hours, the hydrangea extract of Example 1 was treated to FM at concentrations of 12.5, 25, and 50 μg / ml, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 18 hours, mRNA was extracted from the cells and synthesized into cDNA. Quantitative real-time PCR was performed using target primers to finally evaluate the degree of IL-6 gene expression, and the results are shown in Figure 2.

[0131]

[0132] Figure 2 is a graph showing the expression level of IL-6 mRNA derived from IL-1β (Interleukin-1β) following treatment with hydrangea extract.

[0133] As shown in Figure 2, it was confirmed that the hydrangea (Hydrangea serrata) extract significantly inhibits the expression of IL-6 mRNA.

[0134] The above results indicate that the hydrangea serrata extract according to one embodiment effectively inhibits IL-6 mRNA expression, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0135]

[0136] Experimental Example 3. Confirmation of the inhibitory effect of Hydrangea serrata extract and IL-1β (Interleukin-1β) on MMP-3 mRNA expression

[0137] To confirm the inhibitory effect of the hydrangea extract of Example 1 on MMP-3 mRNA expression, MMP-3 mRNA expression was checked after inducing an inflammatory response with IL-1β.

[0138] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a height of 2.0 x 10 5 After attaching to cells at a concentration of 3 ml / well for 24 hours, the hydrangea extract of Example 1 was treated to FM at concentrations of 12.5, 25, and 50 μg / ml, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 18 hours, mRNA was extracted from the cells and synthesized into cDNA. Quantitative real-time PCR was performed using target primers to finally evaluate the level of MMP-3 gene expression, and the results are shown in Figure 3.

[0139]

[0140] Figure 3 is a graph showing the expression level of MMP-3 mRNA derived from IL-1β (Interleukin-1β) following treatment with hydrangea extract.

[0141] As shown in Figure 3, it was confirmed that the hydrangea (Hydrangea serrata) extract significantly inhibits the expression of MMP-3 mRNA.

[0142] The above results indicate that the hydrangea serrata extract according to one embodiment effectively inhibits MMP-3 mRNA expression, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0143]

[0144] Experimental Example 4. Confirmation of the inhibitory effect of Hydrangea serrata extract and IL-1β (Interleukin-1β) on MMP-9 mRNA expression

[0145] To confirm the inhibitory effect of the hydrangea extract of Example 1 on MMP-9 mRNA expression, MMP-9 mRNA expression was checked after inducing an inflammatory response with IL-1β.

[0146] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a height of 2.0 x 10 5 After attaching cells at a concentration of 3 ml / well for 24 hours, the hydrangea extract of Example 1 was treated to FM at concentrations of 12.5, 25, and 50 μg / ml, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 18 hours, mRNA was extracted from the cells and synthesized into cDNA. Quantitative real-time PCR was performed using target primers to finally evaluate the level of MMP-9 gene expression, and the results are shown in Figure 4.

[0147]

[0148] Figure 4 is a graph showing the expression level of MMP-9 mRNA derived from IL-1β (Interleukin-1β) following treatment with hydrangea extract.

[0149] As shown in Figure 4, it was confirmed that the hydrangea (Hydrangea serrata) extract significantly inhibits the expression of MMP-9 mRNA.

[0150] The above results indicate that the hydrangea serrata extract according to one embodiment effectively inhibits MMP-9 mRNA expression, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0151]

[0152] Experimental Example 5. Confirmation of the inhibitory effect of Hydrangea serrata extract and IL-1β (Interleukin-1β) on MMP-13 mRNA expression

[0153] To confirm the inhibitory effect of the hydrangea extract of Example 1 on MMP-13 mRNA expression, MMP-13 mRNA expression was checked after inducing an inflammatory response with IL-1β.

[0154] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a height of 2.0 x 10 5After attaching to cells at a concentration of 3 ml / well for 24 hours, the hydrangea extract of Example 1 was treated to FM at concentrations of 12.5, 25, and 50 μg / ml, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 18 hours, mRNA was extracted from the cells and synthesized into cDNA. Quantitative real-time PCR was performed using target primers to finally evaluate the level of MMP-13 gene expression, and the results are shown in Figure 5.

[0155]

[0156] Figure 5 is a graph showing the expression level of MMP-13 mRNA derived from IL-1β (Interleukin-1β) following treatment with hydrangea extract.

[0157] As shown in Figure 5, it was confirmed that the hydrangea (Hydrangea serrata) extract significantly inhibited the expression of MMP-13 mRNA.

[0158] The above results indicate that the hydrangea serrata extract according to one embodiment effectively inhibits MMP-13 mRNA expression, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0159]

[0160] Experimental Example 6. Confirmation of the inhibitory effect of Hydrangea serrata extract and IL-1β (Interleukin-1β) on PGE2 production

[0161] To confirm the inhibitory effect of the hydrangea extract of Example 1 on PGE2 production, changes in PGE2 were checked after inducing an inflammatory response with IL-1β.

[0162] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a height of 2.0 x 10 5 After attaching cells at a concentration of 3 ml / well for 24 hours, the hydrangea extract of Example 1 was treated to FM at concentrations of 12.5, 25, and 50 μg / ml, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 24 hours, the culture supernatant was obtained, and the amount of PGE2 produced was determined using a PGE2 enzyme-linked immunosorbent assay (ELISA) Kit (Enzo Life Sciences), and the results are shown in Figure 6.

[0163]

[0164] Figure 6 is a graph showing the amount of PGE2 produced from IL-1β (Interleukin-1β) following treatment with hydrangea extract.

[0165] As shown in Figure 6, it was confirmed that the hydrangea (Hydrangea serrata) extract significantly inhibits PGE2 production.

[0166] The above results indicate that the hydrangea serrata extract according to one embodiment effectively inhibits PGE2 production, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0167]

[0168] Experimental Example 7. Confirmation of the inhibitory effect of Hydrangea serrata extract and IL-1β (Interleukin-1β) on COX-2 mRNA expression

[0169] To confirm the inhibitory effect of the hydrangea extract of Example 1 on COX-2 mRNA expression, COX-2 mRNA expression was checked after inducing an inflammatory response with IL-1β.

[0170] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a height of 2.0 x 10 5 After attaching to cells at a concentration of 3 ml / well for 24 hours, the hydrangea extract of Example 1 was treated to FM at concentrations of 12.5, 25, and 50 μg / ml, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 18 hours, mRNA was extracted from the cells and synthesized into cDNA. Quantitative real-time PCR was performed using target primers to finally evaluate the level of MMP-13 gene expression, and the results are shown in Figure 7.

[0171]

[0172] Figure 7 is a graph showing the expression level of COX-2 mRNA derived from IL-1β (Interleukin-1β) following treatment with hydrangea extract.

[0173] As shown in Figure 7, it was confirmed that the hydrangea (Hydrangea serrata) extract significantly inhibits the expression of COX-2 mRNA.

[0174] The above results indicate that the hydrangea serrata extract according to one embodiment effectively inhibits COX-2 mRNA expression, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0175]

[0176] Experimental Example 8. Confirmation of 3D-micro-CT results in an animal model of periodontitis induced by ligation with Hydrangea serrata extract.

[0177] To confirm the inhibitory effect of the hydrangea extract of Example 1 on periodontitis in animals, periodontitis was induced physically, and then 3D-micro-CT results were checked.

[0178] Specifically, sterile distilled water, doxycycline (40 mg / kg), or hydrangea extract (100 mg / kg, 300 mg / kg, 2 rats per group) were orally administered to Sprague Dawley rats (male, 150 g ± 10%). Physical inflammation was induced in the animals' maxillary second molars using a ligation method involving tying sutures. Inflammation induction via ligation was performed a total of four times at one-week intervals, and the degree of inflammation was assessed using 3D-micro-CT after the experiment was completed. The results are shown in Figure 8.

[0179]

[0180] Figure 8 is a graph showing the 3D-micro-CT results in a ligation-induced periodontitis model treated with hydrangea extract.

[0181] As shown in Figure 8A, it was confirmed that Hydrangea serrata extract alleviates alveolar bone loss.

[0182] As shown in Figure 8B, it was confirmed that the hydrangea (Hydrangea serrata) extract increased the BMD value.

[0183] As shown in Fig. 8C, it was confirmed that the hydrangea (Hydrangea serrata) extract reduced the CEJ-ABC value.

[0184] The above results indicate that the hydrangea serrata extract according to one embodiment effectively restores bone loss caused by periodontitis, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0185]

[0186] Experimental Example 9. Confirmation of the inhibitory effect on PGE2 production derived from the active ingredients Thunberginol C and IL-1β (Interleukin-1β) of Hydrangea serrata extract

[0187] To confirm the inhibitory effect of Thunberginol C, the active ingredient of the hydrangea extract in Example 1 above, on PGE2 production, changes in PGE2 were checked after inducing an inflammatory response with IL-1β.

[0188] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a height of 2.0 x 10 5After attaching cells at a concentration of 3 ml / well for 24 hours, the FM was treated with Thunberginol C, the active ingredient of the hydrangea extract from Example 1, at concentrations of 2.5, 10, and 40 μM, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 24 hours, the culture supernatant was obtained, and the amount of PGE2 produced was determined using a PGE2 enzyme-linked immunosorbent assay (ELISA) Kit (Enzo Life Sciences), and the results are shown in Figure 9.

[0189]

[0190] Figure 9 is a graph showing the amount of PGE2 produced from IL-1β (Interleukin-1β) following treatment with the active ingredient Thunberginol C, an active ingredient of hydrangea extract.

[0191] As shown in Figure 9, it was confirmed that Thunberginol C, an active ingredient of Hydrangea serrata extract, significantly inhibits PGE2 production.

[0192] The above results indicate that Thunberginol C, an active ingredient of the Hydrangea serrata extract according to one embodiment, effectively inhibits PGE2 production, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0193]

[0194] Experimental Example 10. Confirmation of the inhibitory effect of Hydrangea serrata extract on PGE2 production derived from the active ingredients Hydrangeic acid and IL-1β (Interleukin-1β).

[0195] To confirm the inhibitory effect of hydrangea acid, the active ingredient of the hydrangea extract in Example 1 above, on PGE2 production, changes in PGE2 were checked after inducing an inflammatory response with IL-1β.

[0196] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a height of 2.0 x 10 5 After attaching cells at a concentration of 3 ml / well for 24 hours, the FM was treated with hydrangea extract active ingredient Hydrangeic acid of Example 1 at concentrations of 2.5, 10, and 40 μM, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 24 hours, the culture supernatant was obtained, and the amount of PGE2 produced was determined using a PGE2 enzyme-linked immunosorbent assay (ELISA) Kit (Enzo Life Sciences), and the results are shown in Figure 10.

[0197]

[0198] Figure 10 is a graph showing the amount of PGE2 produced from IL-1β (Interleukin-1β) following treatment with the active ingredient hydrangea extract, hydrangea acid.

[0199] As shown in Figure 10, it was confirmed that hydrangea serrata extract's active ingredient, hydrangea acid, significantly inhibits PGE2 production.

[0200] The above results indicate that the active ingredient Hydrangea serrata extract, Hydrangeic acid, according to one embodiment, effectively inhibits PGE2 production, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0201]

[0202] Experimental Example 11. Confirmation of the inhibitory effect on PGE2 production derived from the active ingredients Hydrangenol and IL-1β (Interleukin-1β) of Hydrangea serrata extract

[0203] To confirm the inhibitory effect of hydrangenol, the active ingredient of the hydrangea extract in Example 1 above, on PGE2 production, changes in PGE2 were checked after inducing an inflammatory response with IL-1β.

[0204] Specifically, HGF-1 cells, which are gingival fibroblasts, were obtained from the American Type Culture Collection (ATCC, MD, USA), and said HGF-1 cells were cultured in FM (Fibroblast Medium) medium containing 2% FBS, 1% Fibroblast Growth Supplement, and 1% Penicillin / Streptomycin under conditions of 5% CO2 and 37°C. The cultured cells were then placed in 60 pi dishes at a height of 2.0 x 10 5 After attaching cells at a concentration of 3 ml / well for 24 hours, the FM was treated with hydrangenol, the active ingredient of the hydrangea extract from Example 1, at concentrations of 0.01, 0.1, and 1 μM, followed by treatment with IL-1β 10 ng / ml to induce an inflammatory response. After 24 hours, the culture supernatant was obtained, and the amount of PGE2 produced was determined using a PGE2 enzyme-linked immunosorbent assay (ELISA) Kit (Enzo Life Sciences), and the results are shown in Figure 11.

[0205]

[0206] Figure 10 is a graph showing the amount of PGE2 produced from IL-1β (Interleukin-1β) following treatment with the active ingredient hydrangenol, an active ingredient of hydrangea extract.

[0207] As shown in Figure 10, it was confirmed that hydrangenol, an active ingredient of Hydrangea serrata extract, significantly inhibits PGE2 production.

[0208] The above results indicate that the active ingredient hydrangenol of the hydrangea serrata extract according to one embodiment effectively inhibits PGE2 production, thereby having a preventive, improving, or therapeutic effect on periodontitis.

[0209]

[0210] Preparation Example 1. Preparation of tablets

[0211] The hydrangea extract of Example 1, Thunberginol C, hydrangic acid, or hydrangenol were mixed in the component ratios shown in Table 1 below, and tablets were prepared by compressing them according to a conventional tablet manufacturing method. The stability of the prepared tablets was confirmed under all formulation example test conditions.

[0212]

[0213] Ingredient Name Unit Weight (mg) Example 150 Corn Starch 100 Lactose 100 Stearic Acid 2

[0214] Preparation Example 2. Preparation of capsules

[0215] The hydrangea extract of Example 1, Thunberginol C, hydrangic acid, or hydrangenol were mixed in the component ratios shown in Table 2 below and filled into gelatin capsules to produce soft capsules. The prepared capsules were confirmed to be stable under all formulation example test conditions.

[0216]

[0217] Ingredient Name Unit Weight (mg) Example 150 Corn Starch 100 Lactose 100 Stearic Acid 2

[0218] Preparation Example 3. Preparation of Liquid Formulation

[0219] The hydrangea extract of Example 1, Thunberginol C, hydrangic acid, or hydrangenol were mixed in the ingredient ratios shown in Table 3 below, and a liquid formulation was prepared by filling a fruit bottle or pouch according to a beverage preparation method suitable for preference. The stability of the prepared liquid formulation was confirmed under all formulation example test conditions.

[0220]

[0221] List of Ingredients Unit Weight (g) Example 1 2.5050 Xanthan gum 0.0075 Fructooligosaccharide solution 0.7500 Coconut flower extract powder 1.0500 Ssanghwa concentrate 1.5000 Red ginseng flavor 0.0450 Purified water 9.1425

[0222] Preparation Example 4. Preparation of Jelly

[0223] The hydrangea extract of Example 1, Thunberginol C, hydrangic acid, or hydrangenol were mixed in the ingredient ratios shown in Table 4 below, and a jelly was prepared by filling a three-sided cloth according to a jelly preparation method suitable for preference. The stability of the prepared jelly was confirmed under all formulation example test conditions.

[0224]

[0225] List of Ingredients Unit Weight (g) Example 1 2.0000 Food Gel 0.3600 Carrageenan 0.0600 Calcium Lactate 0.1000 Sodium Citrate 0.0600 Complex Scutellaria Root Extract 0.0200 Enzyme-Treated Stevia 0.0440 Fructooligosaccharide Solution 5.0000 Red Grape Concentrate 2.4000 Purified Water 13.9560

[0226] The composition ratios of Manufacturing Examples 1 to 4 above were generally formed by mixing suitable ingredients to create formulation examples, but the mixing ratios and raw materials may be changed arbitrarily as needed.

[0227] Since the extract of the present invention and the components derived therefrom are stable under all formulation example test conditions, there was no problem with the stability of the formulation.

[0228]

[0229] As described above, although the present invention has been explained by limited embodiments and drawings, the present invention is not limited to the above embodiments, and various modifications and variations are possible from this description by those skilled in the art to which the present invention belongs. Therefore, the scope of the present invention should not be limited to the described embodiments, but should be defined by the claims set forth below as well as equivalents thereof.

Claims

1. A health functional food composition for preventing or improving periodontitis comprising, as an active ingredient: hydrangea extract; or Thunberginol C represented by the following chemical formula 1; or hydrangic acid represented by the following chemical formula 2; or hydrangenol represented by the following chemical formula 3; or a food-grade salt thereof. [Chemical Formula 1] [Chemical Formula 2] [Chemical Formula 3] 2. In Paragraph 1, A health functional food composition for preventing or improving periodontitis, wherein the above-mentioned hydrangea extract, the above-mentioned Thunberginol C, the above-mentioned hydrangic acid, or the above-mentioned hydrangenol is extracted with water, a C1 to C4 alcohol, or a mixed solvent thereof.

3. In Paragraph 1, A health functional food composition for preventing or improving periodontitis, wherein the above-mentioned hydrangea extract, the above-mentioned Thunberginol C, the above-mentioned hydrangic acid, or the above-mentioned hydrangenol is included in an amount of 0.0001 to 90 weight% based on the total weight of the health functional food composition.

4. In Paragraph 1, The above hydrangea extract is a health functional food composition for preventing or improving periodontitis, which inhibits TNF-α mRNA expression.

5. In Paragraph 1, The above hydrangea extract is a health functional food composition for preventing or improving periodontitis, which inhibits IL-6 mRNA expression.

6. In Paragraph 1, The above hydrangea extract is a health functional food composition for preventing or improving periodontitis, which inhibits MMP-3 mRNA expression.

7. In Paragraph 1, The above hydrangea extract is a health functional food composition for preventing or improving periodontitis, which inhibits MMP-9 mRNA expression.

8. In Paragraph 1, The above hydrangea extract is a health functional food composition for preventing or improving periodontitis, which inhibits MMP-13 mRNA expression.

9. In Paragraph 1, The above hydrangea extract is a health functional food composition for preventing or improving periodontitis, which inhibits PGE2 production.

10. In Paragraph 1, The above hydrangea extract is a health functional food composition for preventing or improving periodontitis, which inhibits COX-2 mRNA expression.

11. In Paragraph 1, The above hydrangea extract is a health functional food composition for preventing or improving periodontitis, which alleviates bone loss.

12. In Paragraph 1, The above Thunberginol C is a health functional food composition for preventing or improving periodontitis that inhibits PGE2 production.

13. In Paragraph 1, The above hydrangic acid is a health functional food composition for preventing or improving periodontitis that inhibits PGE2 production.

14. In Paragraph 1, The above-mentioned hydrangenol is a health functional food composition for preventing or improving periodontitis, which inhibits PGE2 production.

15. A pharmaceutical composition for the prevention or treatment of periodontitis comprising, as an active ingredient: hydrangea extract; or Thunberginol C represented by the following chemical formula 1; or hydrangic acid represented by the following chemical formula 2; or hydrangenol represented by the following chemical formula 3; or a food-grade acceptable salt thereof. [Chemical Formula 1] [Chemical Formula 2] [Chemical Formula 3] 16. A quasi-drug composition for the prevention or treatment of periodontitis comprising, as an active ingredient: hydrangea extract; or Thunberginol C represented by the following chemical formula 1; or hydrangic acid represented by the following chemical formula 2; or hydrangenol represented by the following chemical formula 3; or a food-grade salt thereof. [Chemical Formula 1] [Chemical Formula 2] [Chemical Formula 3] 17. A topical skin composition for the prevention or treatment of periodontitis comprising, as an active ingredient: hydrangea extract; or Thunberginol C represented by the following chemical formula 1; or hydrangic acid represented by the following chemical formula 2; or hydrangenol represented by the following chemical formula 3; or a food-grade salt thereof. [Chemical Formula 1] [Chemical Formula 2] [Chemical Formula 3]

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