WO2017007140A1 - Composition orale pour la prévention et le traitement de la parodontite, comprenant un extrait d'écorce de racine de mûrier et un extrait de rachis ailé utilisés comme ingrédients actifs - Google Patents

Composition orale pour la prévention et le traitement de la parodontite, comprenant un extrait d'écorce de racine de mûrier et un extrait de rachis ailé utilisés comme ingrédients actifs Download PDF

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Publication number
WO2017007140A1
WO2017007140A1 PCT/KR2016/006266 KR2016006266W WO2017007140A1 WO 2017007140 A1 WO2017007140 A1 WO 2017007140A1 KR 2016006266 W KR2016006266 W KR 2016006266W WO 2017007140 A1 WO2017007140 A1 WO 2017007140A1
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WIPO (PCT)
Prior art keywords
extract
periodontal disease
oral composition
preventing
periodontitis
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PCT/KR2016/006266
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English (en)
Korean (ko)
Inventor
손연경
이종석
이사라
배창환
여주홍
이양구
Original Assignee
대한민국(환경부 국립생물자원관장)
동성제약주식회사
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Priority to CN201680000808.7A priority Critical patent/CN106535911B/zh
Publication of WO2017007140A1 publication Critical patent/WO2017007140A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
    • A61K36/605—Morus (mulberry)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/37—Celastraceae (Staff-tree or Bittersweet family), e.g. tripterygium or spindletree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH

Definitions

  • the present invention relates to an oral composition for the prevention and treatment of periodontal disease comprising cedar extract and arrowwood extract as an active ingredient, more specifically, the extract of cedar extract and arrowwood extract showing an excellent effect on the prevention, improvement and treatment of periodontitis It relates to an oral composition containing as a component.
  • the oral microorganisms produce toxins in the plaque, and the toxins they produce are periodontal disease when they invade the periodontal tissue and cause inflammation of the gingiva, destruction of alveolar bone, and infection, and when these bacteria produce acid, It can also be a cause.
  • microorganisms distributed in the oral cavity cause molar tooth and periodontal disease, and some of these microorganisms are known as opportunistic pathogens and have the potential to develop diseases.
  • Streptococcus mutans and Porphyromonas porphyromonas gingivalis is known to be the main pathogen causing periodontal disease.
  • Periodontitis is complicated and has a variety of symptoms.
  • One of the main causes of periodontitis is caused by microorganisms in the oral cavity. They primarily produce insoluble glucan using sugars and the like and attach to the tooth surface like various cells to form tartar. Tooth decay and periodontitis are caused by these tartars.
  • the most effective way to prevent periodontitis can be achieved by using a substance that inhibits the activity of these microorganisms and improves the blood flow of the inflamed gums.
  • proper oral cleanliness is important for the prevention of periodontitis, but a composition for oral cavity in which various drugs are formulated for the purpose of prophylactic treatment has been proposed.
  • antibiotics such as penicillin, erythromycin, and tetracycline among the drugs used for the prophylactic treatment of periodontitis are effective in inhibiting sterilization and growth, but have a large side effect such as the occurrence of resistant bacteria.
  • antimicrobial agents such as chlorhexidine have been shown to be effective in inhibiting tooth decay, but are highly toxic.
  • Korean Patent Publication No. 10-2012-0022423 composition for oral hygiene comprising the seaweed extract as an active ingredient
  • Korean Patent Publication No. 10-2008-0113504 Garnier Berry Extract as an active ingredient Containing oral bacterium inhibiting composition
  • Morus bark is Morus alba L.) or the root bark of the same plant has long been used in herbal medicine as an anti-inflammatory diuretic, laxative and antitussive expectorant.
  • the winged spindle is a deciduous shrub to the rime vine, and is distributed in Korea, Japan, Sakhalin and China. Young leaves are herbs and the wings of branches are called earheads. The leaves contain epipriedelanol, priedelin, quercetin and dulcitol. Seed oil contains saturated fatty acids (20%), oleic acid, linoleic acid, linolenic acid, capric acid and benzoic acid. Oriental medicine is used for hemostasis, gore blood, pain.
  • the present inventors have completed the present invention by confirming the efficacy using the baekbaekpi and arrowwood exhibiting the above-described efficacy in order to develop a drug exhibiting an excellent antimicrobial effect against the periodontitis causing bacteria.
  • Oral composition for preventing and treating periodontal disease or periodontal disease prevention and improvement of the health functional food of the present invention to achieve the above object including the extract of cedar and arrow extract as an active ingredient, showing the growth inhibitory activity of periodontitis-inducing bacteria Is characteristic.
  • the periodontitis causing bacteria is Porphyromonas ( Phyphyromonas) gingivalis).
  • the cedar extract and arrowwood extract is characterized by consisting of 1: 1 weight ratio.
  • the lettuce extract or arrow extract is characterized in that extracted with ethanol.
  • the oral composition is characterized by having any one or more formulations selected from toothpaste, chewing gum, mouthwash, mouthwash and mouth spray.
  • the dietary supplement is characterized by having any one or more formulations selected from powders, granules, tablets, capsules or beverages.
  • an oral composition or a health functional food which includes an extract of cedar extract and arrowwood extract as an active ingredient, and which exhibits an excellent effect on the prevention, improvement and treatment of periodontitis.
  • an extract of cedar extract and arrowwood extract as an active ingredient, and which exhibits an excellent effect on the prevention, improvement and treatment of periodontitis.
  • 1 is a graph showing the antimicrobial activity of lettuce extract.
  • Figure 2 is a graph showing the antimicrobial activity of arrowwood extract.
  • Figure 3 is a graph showing the antimicrobial activity of the mixed extract (10 ppm) consisting of cedar extract (5 ppm) + arrow extract (5 ppm).
  • Figure 4 is a graph showing the antimicrobial activity of the mixed extract (50 ppm) consisting of lettuce extract (25 ppm) + arrowwood extract (25 ppm).
  • the present invention provides an oral composition for preventing and treating periodontal disease, including the extract of cedar extract and arrowwood extract as an active ingredient.
  • the baekpipi extract or arrowwood extract is dried by extracting the baekpipi or arrowwood, respectively, 5 to 15 times the solvent of each weight (g), preferably water, lower alcohol of C1 to C4 or a mixed solvent thereof Extracts soluble in a solvent selected from, more preferably 1 to 10 times, preferably 3 to 10 hours at 10 to 50 ° C, preferably 20 to 30 ° C, preferably 3 to 36 hours with ethanol Can be obtained by repeated extraction five times.
  • the extract of the cedar extract When the extract is used as an active ingredient and the extract of the cedar extract is used as an active ingredient, the extract of the cedar extract should be contained in a high concentration in the antibacterial activity against periodontitis-inducing bacteria, the arrow extract extract has antibacterial activity even at 100ppm concentration Not shown.
  • the mixture of the lettuce extract and the arrowwood extract oral compared to conventional toothpaste.
  • the stability of the active ingredient will be able to obtain the prevention and treatment of periodontitis.
  • the extract from the cedar extract and the arrowwood extract in a 1: 1 weight ratio and use it as an active ingredient for oral composition for the prevention and treatment of periodontitis.
  • Porphyromonas gingivalis Porphyromonas gingivalis is characterized by showing antimicrobial activity.
  • the oral composition containing the extract of the present invention may be prepared by using a formulation such as toothpaste, chewing gum, mouthwash, mouthwash and mouth spray, but is not limited thereto.
  • Toothpaste of the present invention comprises a composition selected from the group consisting of abrasives, binders, moisturizers, active ingredients, foaming agents, sweeteners, flavoring agents.
  • Abrasives include aluminum hydroxide, silicic anhydride, aluminum silicate, dibasic calcium phosphate, dihydrate and anhydride, tricalcium phosphate, calcium carbonate, calcium pyrophosphate, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate and calcium sulfate , Polymethyl methacrylate, and other synthetic resins may be used in combination of one or two or more of them in an amount of about 20-90% of the total composition (20-60% in the case of paste toothpaste).
  • synthetic polymers such as a garginine, various cellulose derivatives for thickening, gums, such as a xanthan gum and a tragacanth gum, polyvinyl alcohol, sodium polyacrylate, a polyacrylic acid / maleic acid copolymer, and carboxyvinyl polymer
  • organic binders such as derivatives
  • inorganic binders such as a silica and a laponite, 1 type, or 2 or more types can be mix
  • Paste and liquid oral compositions in dentifrices include sorbitol, glycerin, ethylene glycol, propylene glycol, polyether glycol, polypropylene glycol, and the like as moisturizing agents in the preparation of about 10-70% of the total composition. It can be used in combination.
  • oral compositions containing the extract of the present invention include menthol (Mentol), anetol (Anetol), eugenol (Eugenol), limonene (Limonene), Ocimene, n-dodecyl alcohol (n-Dodecy Alcohol, Citronenol, Alpha-Terpineol, Methyl salycilate, Methyl Acetate, Citroneryl Acetate, Cineol, Linalol, Ethyl Linalool, Vanillin, Thymol, Spearamint Oil, Sage Oil, Rosemary Oil, Cinnamon Oil, etc.
  • the agents may be used alone or in combination in amounts of 0.1-10%, preferably 0.5-5%, of the total composition.
  • sweeteners such as sodium saccharin, stevioside, aspartame, D-Xylose and the like can be used in combination in an amount of 0-1%, preferably 0.01-0.5% of the total composition.
  • oral compositions of the present invention include trichloric acid, chlorohexidine, benzetonium chloride, benzalkonium chloride, cationic fungicides such as cetylpyridium chloride, alkali metal monofluoro such as sodium monofluorophosphate and potassium monophosphate, etc.
  • Fluorides such as phosphate, sodium fluoride and tin fluoride, tranexamic acid, epsilon amino capronic acid, aluminum chlorohydroxy allantoin, dihydro cholestanol, cletylithic acid, glycerophosphate, sodium chloride, and water-soluble inorganic phosphate compounds
  • one or two or more of various potent ingredients such as ascorbic acid (sodium), dl-a-tocopherol acetate, xylitol, pyridoxine hydrochloride and polyvinyl pyrrolidone can be used in combination.
  • the surfactant used as the foaming component in the oral composition of the present invention may be used anionic surfactants, nonionic surfactants and / or zwitterionic surfactants.
  • the anionic surfactants include sodium lauryl sulfate, sodium alkyl sulfates such as myristyl sulfate, sodium N-Lauroyl sarcosinate, sodium N-miristyl sarcosinate, and the like.
  • Sodium N-acyl sarcosinate may be used
  • non-ionic surfactants include sugar-derived fatty acid esters such as sugar fatty acid esters, maltose fatty acid esters, lactose fatty acid esters, and polyesters.
  • Oxy ethylene hardened castor oil, polyoxyethylene higher alcohol ether, polyoxy ethylene polyoxy propylene copolymer, polyoxy ethylene polypropylene fatty acid ester and the like can be used.
  • Zwitterionic surfactants include N-alkyl diaminoethylglycine, such as N-lauryl di aminoethylglycine, N-myristyl diaminoethylglycine, N-alkyl-N-carboxy methyl ammonium betaine, 2-alkyl-1 -Hydroxy ethyl imidazoline betaine sodium, etc. can be used.
  • anionic surfactants are mainly used as the foaming component, and sodium alkyl sulfates such as sodium lauryl sulfate are most widely used.
  • these surfactant is used individually by 1 type or in mixture of 2 or more types, and the compounding quantity normally uses 0.01-0.5% of a whole composition, More preferably, 0.05-0.3%.
  • the present invention provides a health functional food for the prevention and improvement of periodontitis containing the extract as an active ingredient.
  • Health functional foods including the extract of the present invention can be used in a variety of drugs, foods and drinks for the prevention and improvement of periodontitis.
  • Foods to which the extract of the present invention may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and may be used in the form of powders, granules, tablets, capsules, or beverages. have.
  • the extract itself of the present invention has little toxicity and side effects, it is a drug that can be used safely even when taken for long periods of time.
  • the extract of the present invention may be added to food or beverage for the purpose of preventing and improving periodontitis.
  • the amount of the extract in the food or beverage is generally the health food composition of the present invention can be added to 0.01 to 15% by weight of the total food weight, the health beverage composition is 0.02 to 10 g, preferably based on 100 ml It can be added at a ratio of 0.3 to 1 g.
  • the health beverage composition of the present invention in addition to containing the extract or compound as an essential ingredient in the indicated ratio, there is no particular limitation on the liquid component, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates are conventional monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and polysaccharides such as dextrin, cyclodextrin and the like.
  • Sugars and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents such as, tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.
  • the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like.
  • the health functional food of the present invention may contain natural fruit juice and fruit flesh for producing fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
  • the powder was ground in a grinder, and then 1 kg of the baekbaekpi powder was placed in 10 L of 70% ethanol and extracted under reflux for 3 hours at room temperature. The extract was repeated three times.
  • the extract was filtered to recover only the extract filtrate, and then distilled under reduced pressure to prepare a liquid extract extract (receiving concentration: 10000 ppm).
  • the prepared lettuce extract was diluted by 10 times step by step using sterile distilled water was prepared by concentration (0.1, 1, 10, 100, 1000, 10000 ppm).
  • the arrow branches were washed with purified water and then naturally dried at room temperature for 7 days.
  • the powder was ground in a grinder, and then 1 kg of the arrowwood powder was placed in 10 l of 70% ethanol, and extracted under reflux for 3 hours at room temperature. The extract was repeated three times.
  • the extract was filtered to recover only the extract filtrate and distilled under reduced pressure to prepare a liquid arrow extract (receiving concentration: 10000 ppm).
  • the manufactured arrow extract was diluted by 10 times step by step using sterile distilled water was prepared by concentration (0.1, 1, 10, 100, 1000, 10000 ppm).
  • MIC tests were performed to determine the antimicrobial activity of periodontal fungi of lettuce extract, arrow extract and mixed extracts.
  • a strain of periodontal-induced bacterium Popiromonas jinjibaris which was distributed by the ATCC American Microbial Resource Center (ATCC BAA-1703 TM ), was used.
  • Porphyromonas jinjibaris, the periodontitis-inducing bacterium gingivalis) strains were inoculated in Brain heart infusion broth medium containing 5ug / ml hemin and 1ug / ml vitamin K, and then cultured at 37 ° C.
  • the diluted solution was diluted 10 times step by step using the stock solution and sterile distilled water.
  • test tube containing the mixed solution of 1, including the bacterial culture solution, the extract and the sterilized liquid medium, was incubated at 37 ° C. for 30 hours.
  • Antibiotic determination was carried out every 3 hours of culture, 0.1 ml of the mixed solution of each treatment was measured using a 96 well palte to measure the change in absorbance due to bacterial growth at 600 nm.
  • Figure 2 is Porphyromonas jinjibaris gingivalis ) As a test for the antimicrobial activity of the arrowwood extract in the strain, it was confirmed that almost no antimicrobial activity at low concentrations of 10 ppm, 25 ppm, 50 ppm.
  • composition for preventing and treating periodontitis prepared according to the present invention when using the composition for preventing and treating periodontitis prepared according to the present invention, it is expected to exhibit excellent antimicrobial activity against the strain causing periodontitis, and to obtain the effect of preventing and treating periodontitis.
  • it can be used as a material such as, it is possible to expect an increase in added value.
  • the components belonging to a of Table 1 were added to the production unit at a temperature of 70 to 75 ° C., and stirred for 20 minutes to completely dissolve the powder and then cooled to room temperature.
  • the components belonging to b including the carrier obtained in Example 1 were added to the production unit at 25 to 30 ° C., followed by stirring for 15 minutes to dissolve.
  • the components belonging to c were mixed at 25 to 35 ° C. and added in stages.
  • the next process was a foaming agent mixing and primary degassing process, in which the components belonging to d were added to complete the primary defoaming during the 40 minute process at 25 to 35 ° C.
  • the final process is a fragrance mixing process, to which toothpaste was prepared by adding a component belonging to e and degassing at 25 to 35 ° C.
  • composition was according to Table 1 below.

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Abstract

L'invention concerne une composition orale pour la prévention et le traitement de la parodontite, qui comprend un extrait d'écorce de racine de mûrier et un extrait de rachis ailé utilisés comme ingrédients actifs. Elle concerne plus particulièrement une composition orale qui comprend un extrait d'écorce de racine de mûrier et un extrait de rachis ailé utilisés comme ingrédients actifs, et présente un excellent effet de prévention, d'atténuation et de traitement de la parodontite. L'invention concerne une composition orale ou un aliment fonctionnel naturel présentant un excellent effet de prévention, d'atténuation et de traitement de la parodontite.
PCT/KR2016/006266 2015-07-08 2016-06-13 Composition orale pour la prévention et le traitement de la parodontite, comprenant un extrait d'écorce de racine de mûrier et un extrait de rachis ailé utilisés comme ingrédients actifs WO2017007140A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201680000808.7A CN106535911B (zh) 2015-07-08 2016-06-13 含有作为活性成分的桑白皮提取物与卫矛提取物的牙周炎预防及治疗用口腔组合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020150096890A KR101641213B1 (ko) 2015-07-08 2015-07-08 상백피추출물과 화살나무추출물을 유효성분으로 포함하는 치주염 예방 및 치료용 구강조성물
KR10-2015-0096890 2015-07-08

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WO2017007140A1 true WO2017007140A1 (fr) 2017-01-12

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KR102022006B1 (ko) 2017-09-07 2019-09-18 태이생명과학 주식회사 아스퍼질러스 나이거 분리 효소 처리된 황금 추출물을 유효성분으로 포함하는 치주질환 예방 또는 치료용 조성물
KR20190058127A (ko) 2017-11-21 2019-05-29 동의대학교 산학협력단 산청목 추출물을 포함하는 구강질환의 예방 또는 치료용 조성물
KR102097387B1 (ko) 2018-05-04 2020-04-06 원광대학교산학협력단 흑미를 유효성분으로 하는 구강질환 예방 및 치료를 위한 조성물
KR102166701B1 (ko) 2018-06-18 2020-10-16 스노우화이트팩토리(주) 아스퍼질러스 나이거 균주를 이용한 황금 발효 추출물을 유효성분으로 포함하는 치주 질환 예방 또는 치료용 조성물
KR20210133852A (ko) * 2020-04-29 2021-11-08 한국 한의학 연구원 화살나무 추출물을 유효성분으로 함유하는 골질환의 예방, 개선 또는 치료용 조성물

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