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WO2017061781A1 - Composition pharmaceutique permettant de favoriser la croissance des tissus parondontaux, ainsi que la prévention et le traitement de la parondontite, contenant comme principe actif un extrait de fleur de magnolia, une fraction de ce dernier, ou un composé isolé à partir de ce dernier - Google Patents

Composition pharmaceutique permettant de favoriser la croissance des tissus parondontaux, ainsi que la prévention et le traitement de la parondontite, contenant comme principe actif un extrait de fleur de magnolia, une fraction de ce dernier, ou un composé isolé à partir de ce dernier Download PDF

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Publication number
WO2017061781A1
WO2017061781A1 PCT/KR2016/011171 KR2016011171W WO2017061781A1 WO 2017061781 A1 WO2017061781 A1 WO 2017061781A1 KR 2016011171 W KR2016011171 W KR 2016011171W WO 2017061781 A1 WO2017061781 A1 WO 2017061781A1
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WO
WIPO (PCT)
Prior art keywords
root
periodontitis
extract
active ingredient
periodontal tissue
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2016/011171
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English (en)
Korean (ko)
Inventor
최봉근
우제태
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
OKINAWA RESEARCH CENTER Co Ltd
Original Assignee
OKINAWA RESEARCH CENTER Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020160040438A external-priority patent/KR101826229B1/ko
Application filed by OKINAWA RESEARCH CENTER Co Ltd filed Critical OKINAWA RESEARCH CENTER Co Ltd
Priority to US15/766,605 priority Critical patent/US20180296623A1/en
Priority to JP2018538509A priority patent/JP6608071B2/ja
Priority to CN201680071460.0A priority patent/CN108367040A/zh
Priority to EP16853897.3A priority patent/EP3360562A4/fr
Publication of WO2017061781A1 publication Critical patent/WO2017061781A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • 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)
    • A61K36/57—Magnoliaceae (Magnolia family)
    • A61K36/575—Magnolia
    • 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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • 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

Definitions

  • the present invention relates to a pharmaceutical composition for promoting growth of the root or periodontal tissue, or preventing or treating periodontitis, which contains a Magnolia flower extract, a fraction thereof or a compound separated therefrom as an active ingredient.
  • Periodontal tissue is a complex organ comprising both soft and hard tissue consisting of gums, gums, periodontal ligaments and alveolar bone.
  • Gingival is a simple connective tissue involved in the support and chewing process of the tooth, while the periodontal ligament is located between the tooth and the alveolar bone to support and attach the tooth to the jaw bone, resists mechanical stress in various directions such as chewing force, and also sense function It is a highly differentiated cellular connective tissue.
  • These periodontal ligaments include osteoblasts and osteoclasts on the alveolar bone side, fibroblasts on the central side of the periodontal ligament, epithelial rests of Malassez, macrophages, undifferentiated mesenchymal cells, and nerve elements.
  • vascular endothelial cells It is known to be involved in the repair and regeneration of alveolar bone, root and chalkiness, composed of various cells such as cementoblasts located on the root side.
  • the gum is the part of the supportive tissue that we see in our mouth, where the disease (gingivitis) begins, and when the disease grows deeper and spreads deeply into the supportive tissue, the periodontal ligament is coupled to the root of the tooth and the bone tissue surrounding the tooth. Destroyed alveolar bone is also destroyed and the periodontal disease occurs.
  • Periodontal disease refers to an inflammatory state of supportive tissue caused by bacteria and can be divided into gingivitis and periodontitis. The cause is due to poor oral hygiene state oral bacteria to form a dental plaque. Toothpaste bacterium refers to a mass of bacteria that grows after the bacteria adhere to the tooth surface by using a sticky substance in the saliva as an adhesive. If left untreated, the bacterial membranes are inflamed and sometimes bleed from the gums and cause bad breath. These symptoms are called gingivitis.
  • Periodontitis As the gingivitis progresses further, the gap between the teeth and the gums deepens and the periodontal sac develops, and the periodontal disease occurs because the bacteria that cause periodontal disease multiply. As periodontitis progresses, even weak stimuli such as brushing may bleed and swell the gums, often turning into acute inflammation, causing pain. This inflammation lowers the function of making bones, and the bone absorbing effect is increased, the alveolar bone becomes lower and lower, and the alveolar bone is destroyed and eventually loses teeth. Advanced periodontitis causes tooth loss. Tooth loss due to periodontitis is a serious problem, as it is reported that the percentage of periodontitis is 40% of the causes of tooth extraction in adults after the age of 40.
  • periodontal disease has been used for the establishment of improved oral hygiene, non-surgical or surgical calculus removal, root graft, gingival sopa and regeneration of periodontal tissue.
  • these surgical methods of treatment are difficult to treat effectively due to the hassle of going to the dentist for treatment, and are limited to the treatments performed when the disease progresses rather than preventing the disease.
  • Most of the time systemic antibiotics and topical sustained-release drugs have been used, but cases of periodontal disease bacteria have been reported that result in too much drug delivery to unnecessary areas resulting in side effects and resistance to recently used antibiotics. There is a serious problem.
  • the burden on the patient increases rapidly due to prosthetic treatment or dental implant treatment, and in particular, it may be a higher medical barrier for the socially vulnerable. Therefore, if the damaged tissue can be regenerated before the loss of teeth, the need for treatment such as artificial teeth or prostheses can be reduced, thereby reducing the economic and social burden.
  • Periodontal disease enters the healing phase through non-surgical or surgical removal of inflammatory connective tissue such as plaque and tartar, but lost periodontal tissue is not a regeneration of individual periodontal tissue components. Proliferation of epithelial tissues results in incomplete healing.
  • Magnolia flower is the word for magnolia flowers belonging to the Magnoliaceae, and it is said to be sour because the buds are slightly spicy.
  • dried magnolias Magnnolia denudata Desrousseaux or buds of the same plant are dried.
  • M. denudata Desr, Manchunhua (M. flower Pamp., ⁇ ) and ladybugs (M. sprengeri Pamp., ⁇ ⁇ ) are used.
  • Chinese medicine for Shinyi is considered to be warm, and it is reported that it is effective for headache, low back pain and rhinitis, and to treat sinusitis and weakness of analgesics.
  • U.S. Patent No. 13 / 739,340 relates to a pharmaceutical composition that promotes osteoogenesis, wherein extracts obtained from the leaves or bark of magnolia and plants have an effect of promoting bone density and bone growth without side effects. It is starting.
  • the bone of the human body maintains its homeostasis through bone modeling and bone remodeling through the action of osteoblasts and osteoclasts.
  • cartilage occurs in the form of bone, after which calcium deposition occurs, the cartilage is lost and develops into bone, and the chondrocytes turn into osteoblasts.
  • Tooth formation is produced through a process different from the bone formation process. Specifically, when development begins at 6 weeks of birth, the epithelium on the surface enters in, and the cells begin to proliferate in the internal connective tissue, and the cells in the epidermis grow further as the cells embedded in the epithelium grow. Is formed. The epithelial cells differentiate into enamel cells that later envelop the teeth, and inside, the progenitor cells and dendritic cells that form dentin are differentiated. As such, it can be seen that bone formation and tooth formation are completely different cells and mechanisms involved.
  • the present invention provides a pharmaceutical composition for promoting growth of the root or periodontal tissue, or preventing or treating periodontitis, which contains a Magnolia flower extract or a fraction separated therefrom as an active ingredient.
  • the present invention also provides an quasi-drug composition for promoting growth of the root or periodontal tissue, or preventing or improving periodontitis, which contains an extract or a fraction separated therefrom as an active ingredient.
  • the present invention provides a health functional food for promoting growth of the root or periodontal tissue, or preventing or improving periodontitis, which contains the extract of the god or the fraction separated therefrom as an active ingredient.
  • the present invention provides a cosmetic composition for promoting growth of periodontal or periodontal tissue, or periodontitis, which contains an extract or a fraction separated therefrom as an active ingredient.
  • the present invention provides a compound represented by the following formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof to promote the growth of the root or periodontal tissue containing as an active ingredient, or to prevent or treat periodontitis
  • a composition :
  • the present invention is a quasi-drug composition for promoting the growth of root or periodontal tissue, or preventing or improving periodontitis, the compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient.
  • the present invention is to promote the growth of the root or periodontal tissue containing the compound represented by Formula 1 or 2, pharmaceutically acceptable salts thereof, or optical isomer thereof as an active ingredient, or health function for preventing or improving periodontitis Provide food.
  • the present invention provides a cosmetic composition for promoting growth of periodontal or periodontal tissue containing the compound represented by Formula 1 or 2, a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient, or improving periodontitis. .
  • step 2) adding a mixed solvent of ethyl acetate and hexane to the methanol fraction of step 1) to obtain an eluate;
  • the present invention also provides a method for promoting growth of the root or periodontal tissue, or preventing or treating periodontitis, comprising administering to a subject a pharmaceutically effective amount of a god extract or a fraction separated therefrom.
  • the present invention provides a use of the pharmaceutical composition comprising an extract or a fraction separated from the god god as an active ingredient for promoting growth of the root or periodontal tissue, or preventing or treating periodontitis.
  • the present invention provides a use of the quasi-drug composition comprising an extract or a fraction separated from the god as an active ingredient for promoting growth of the root or periodontal tissue, or preventing or improving periodontitis.
  • the present invention provides a use for the use of a health functional food comprising a god extract or fractions separated therefrom as an active ingredient for promoting growth of the root or periodontal tissue, or preventing or improving periodontitis.
  • the present invention provides a use of the cosmetic composition comprising a god extract or a fraction separated therefrom as an active ingredient for use in promoting growth of the root or periodontal tissue, or improving periodontitis.
  • the present invention comprises the step of administering a pharmaceutically effective amount of the compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof to the individual, promoting growth of the root or periodontal tissue Or preventing or treating periodontitis.
  • the present invention provides a pharmaceutical composition containing the compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient to promote growth of the root or periodontal tissue, or to prevent periodontitis or Provides uses for use in therapy.
  • the present invention is to promote the growth of the root or periodontal tissue, or prevent or improve periodontitis of the quasi-drug composition containing the compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient.
  • the present invention provides a functional food containing the compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient to promote the growth of the root or periodontal tissue, or to prevent periodontitis or Provides use for use in improvement.
  • the present invention uses a compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or a cosmetic composition containing an optical isomer thereof as an active ingredient to promote growth of the root or periodontal tissue, or improve periodontitis It provides a use for.
  • Magnolia flower extract of the present invention fractions thereof and the compound represented by the following formula (1) or (2) promote the growth of the root, form alveolar bone around the teeth to promote periodontal tissue growth and periodontitis Since there is an inhibitory effect, the extract of Sinyi, its fractions and compounds may be usefully used as an active ingredient in the promotion of growth of the root or periodontal tissue, or a pharmaceutical composition for the prevention or treatment of periodontitis:
  • 1 is a view showing the structure of a human tooth.
  • Figure 2 is a diagram showing the manufacturing process of the extract of Sin, its fractions and compounds.
  • Figure 3 shows the results of implantation in the host mouse after embedding the teeth in agarose beads containing fargesin compound (agarose beads):
  • PBS teeth embedded in agarose beads containing PBS
  • Fargesin A tooth embedded in agarose beads containing fargesin.
  • FIG. 4 is a diagram showing the results of transplantation in the host mouse after embedding the teeth in agarose beads containing the god extract:
  • PBS teeth embedded in agarose beads containing PBS
  • Fargesin teeth embedded in agarose beads containing fargesin
  • the present invention provides a pharmaceutical composition for promoting growth of the root or periodontal tissue, or preventing or treating periodontitis, which contains Magnolia flower extract or a fraction separated therefrom as an active ingredient.
  • the present invention also provides a method for promoting growth of the root or periodontal tissue, or preventing or treating periodontitis, comprising administering to a subject a pharmaceutically effective amount of a god extract or a fraction separated therefrom.
  • the present invention provides a use of the pharmaceutical composition comprising an extract or a fraction separated from the god god as an active ingredient for promoting growth of the root or periodontal tissue, or preventing or treating periodontitis.
  • the god may be used without limitation, such as cultivated or commercially available, and may be used any part such as the stem, leaves, roots, buds of the god, but according to a preferred embodiment of the present invention It is characterized by.
  • the extraction method of the Sinyi extract may be used a conventional method in the art, such as filtration, hot water extraction, dipping extraction, reflux cooling extraction and ultrasonic extraction, may be one to five times by hot water extraction method, more Specifically, the extraction may be repeated three times, but is not limited thereto.
  • the extracting solvent may be added 0.1 to 10 times to the dried sinus, preferably 0.3 to 5 times.
  • Extraction temperature may be 20 to 40 °C
  • extraction time may be 12 to 48 hours.
  • the god extract or fraction may be prepared by a manufacturing method comprising the following steps:
  • the drying of step 1) may be, but not limited to, drying under reduced pressure, vacuum drying, boiling drying, spray drying or freeze drying.
  • the extraction solvent of step 2) may be water, a lower alcohol of C 1 ⁇ C 2 or a mixture thereof.
  • the reduced pressure concentration of step 3 may be to use a vacuum pressure reducer or a vacuum rotary evaporator.
  • the organic solvent of step 4) may be ethyl acetate, hexane, benzene or chloroform.
  • the fraction may be a fraction obtained by dividing the extract with ethyl acetate and then further fractionated with methanol, or the fraction eluted with ethyl acetate and hexane in a ratio of 3: 7 or 5: 5.
  • the inventors found that when roots were incubated in agarose beads containing a god extract, the root growth was remarkable and alveolar bone was newly formed around the teeth (see FIG. 4). ), The extract was found to have an effect of promoting the growth of the root or periodontal tissue.
  • the periodontal ligament that can help the growth of the teeth and roots in the future, as well as tooth extraction, which is not only extracted from the teeth embedded in the alveolar bone when extracted 5 days old mouse is attached to the teeth Extracted together.
  • the extracted mouse teeth grow the root and periodontal tissue by the sample, and this helps the root growth by the interaction of various cells included in the periodontal ligament.
  • the outer surface of the root is covered with a hard tissue called chalky, it is connected to the periodontal ligament serves to fix the teeth, the chalky is also formed by the periodontal ligament cells. Therefore, due to the interaction of various cells in the periodontal ligament, not only the root but also the chalky surrounding the root are formed. As such, the periodontal ligament may be an important factor for the growth of root and periodontal tissue.
  • Sinyi extract or fractions thereof may be usefully used as a pharmaceutical composition for promoting growth of the root or periodontal tissue, or preventing or treating periodontitis.
  • composition of the present invention contains 0.1 to 99.9% by weight of the god extract or fraction of the present invention based on the total weight of the composition as an active ingredient, and may include a pharmaceutically acceptable carrier, excipient or diluent.
  • compositions of the present invention may be in various oral or parenteral formulations.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
  • Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin.
  • lubricants such as magnesium stearate, talc and the like are also used.
  • Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • composition of the present invention may be administered orally or parenterally, and it is preferable to select externally or intraperitoneally, rectally, intravenously, intramuscularly, subcutaneously, intrauterine epidural or cerebrovascular injection methods for parenteral administration. For skin use externally.
  • the dosage of the composition of the present invention varies depending on the weight, age, sex, health condition, diet, time of administration, administration method, excretion rate and severity of the disease of the patient, the daily dosage is the amount of the extract or fraction of god 0.01 to 1000 mg, preferably 30 to 500 mg / kg, more preferably 50 to 300 mg / kg, and may be administered 1 to 6 times per day.
  • compositions of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers.
  • the present invention also provides an quasi-drug composition for promoting growth of the root or periodontal tissue, or preventing or improving periodontitis, which contains an extract or a fraction separated therefrom as an active ingredient.
  • the present invention provides a use of the quasi-drug composition comprising an extract or a fraction separated from the god as an active ingredient for promoting growth of the root or periodontal tissue, or preventing or improving periodontitis.
  • the quasi-drug composition is preferably in the form of a composition for oral cavity, such as toothpaste, mouthwash or mouthwash.
  • the quasi-drug composition containing the extract or fraction provided by the present invention is not particularly limited in the formulation and may have a conventional formulation, specifically, may have a formulation such as toothpaste, mouthwash or mouthwash.
  • the oral composition provided by the present invention may contain various bases and additives necessary for formulation according to the formulation, and the type and amount of these components can be easily selected by those skilled in the art.
  • the formulation of the composition for oral cavity is a toothpaste, it can be prepared by adding an abrasive, a humectant, a foaming agent, a binder, a sweetening agent, a pH adjusting agent, a preservative, an active ingredient, a fragrance, a brightener, a pigment, a solvent and the like.
  • the present invention provides a health functional food for promoting growth of the root or periodontal tissue, or preventing or improving periodontitis, which contains the extract of the god or the fraction separated therefrom as an active ingredient.
  • the present invention provides a use for the use of a health functional food comprising a god extract or fractions separated therefrom as an active ingredient for promoting growth of the root or periodontal tissue, or preventing or improving periodontitis.
  • the health functional food of the present invention may contain various flavors or natural carbohydrates as additional ingredients.
  • the above-mentioned natural carbohydrates are sugars such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose and polysaccharides such as dextrin and cyclodextrin, xylitol, sorbitol and erythritol.
  • sugars such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose and polysaccharides such as dextrin and cyclodextrin, xylitol, sorbitol and erythritol.
  • natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin, aspartame, and the like can be used.
  • the ratio of the natural carbohydrate can be selected from 0.01 to 0.04 parts by weight, specifically about 0.02 to 0.03 parts by weight per
  • the health functional food of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, And a carbonation agent used for the carbonated beverage.
  • these components can be used independently or in combination.
  • the ratio of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health food of the present invention.
  • Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.
  • the present invention provides a cosmetic composition for promoting growth of periodontal or periodontal tissue, or periodontitis, which contains an extract or a fraction separated therefrom as an active ingredient.
  • the present invention provides a use of the cosmetic composition comprising a god extract or a fraction separated therefrom as an active ingredient for use in promoting growth of the root or periodontal tissue, or improving periodontitis.
  • the cosmetic composition may include, but is not limited to, lotions, ointments, gels, creams, patches or sprays.
  • a cosmetic composition containing the extract of the god of the present invention or a fraction separated therefrom it is usually 3 to 30 parts by weight, preferably 5 Or 20 parts by weight.
  • the cosmetic composition of the present invention contains a fatty material, an organic solvent, a dissolving agent, a thickening agent and a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizing agent, and a foaming agent in addition to the extract of the god of the present invention or a fraction separated therefrom.
  • Fragrances surfactants, water, ionic or nonionic emulsifiers, fillers, metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles Or adjuvants commonly used in the field of dermatology, such as any other ingredients conventionally used in cosmetic compositions.
  • the ingredients may also be introduced in amounts generally used in the field of dermatology.
  • the present invention provides a compound represented by the following formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof to promote the growth of the root or periodontal tissue containing as an active ingredient, or to prevent or treat periodontitis To provide a composition.
  • the present invention comprises the step of administering to a subject a pharmaceutically effective amount of a compound represented by the following formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof, to promote root growth or periodontal tissue Or preventing or treating periodontitis.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound represented by the following formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient to promote growth of the root and periodontal tissue, or to prevent periodontitis or Provides uses for use in therapy.
  • the compound represented by the following Chemical Formula 1 or 2 may be isolated from the extract god.
  • the present inventors have found that when the tooth is embedded in agarose beads containing fargesin isolated from the extract, the root growth is remarkable, and alveolar bone is newly formed around the tooth. (See FIG. 3), the compound represented by Chemical Formula 1 or 2 may be usefully used as an active ingredient for promoting growth of the root or periodontal tissue, or preventing or treating periodontitis.
  • the compound represented by any one of Formulas 1 to 2 of the present invention may be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful.
  • Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid and aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanediodes.
  • non-toxic organic acids such as acids, aromatic acids, aliphatic and aromatic sulfonic acids, acetic acid, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid.
  • Such pharmaceutically nontoxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, and iodide.
  • Acid addition salt according to the present invention is dissolved in an organic solvent, such as methanol, ethanol, acetone, methylene chloride, acetonitrile, etc. in a conventional method, for example, a compound represented by any one of formulas (1) to (2)
  • an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile, etc.
  • the precipitate produced by addition may be prepared by filtration and drying, or the solvent and excess acid may be distilled under reduced pressure, and then dried or crystallized under an organic solvent.
  • Bases can also be used to make pharmaceutically acceptable metal salts.
  • Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving a compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare sodium, potassium or calcium salt as the metal salt.
  • Corresponding silver salts are also obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).
  • the present invention includes not only the compound represented by any one of Formulas 1 and 2, and pharmaceutically acceptable salts thereof, but also all possible solvates, hydrates, isomers, and the like that can be prepared therefrom.
  • the present invention is a quasi-drug composition for promoting the growth of root or periodontal tissue, or preventing or improving periodontitis, the compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient.
  • the present invention is to promote the growth of the root or periodontal tissue, or prevent or improve periodontitis of the quasi-drug composition containing the compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient.
  • the present invention is to promote the growth of the root or periodontal tissue containing the compound represented by Formula 1 or 2, pharmaceutically acceptable salts thereof, or optical isomer thereof as an active ingredient, or health function for preventing or improving periodontitis Provide food.
  • the present invention provides a functional food containing the compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient to promote the growth of the root or periodontal tissue, or to prevent periodontitis or Provides use for use in improvement.
  • the present invention provides a cosmetic composition for promoting growth of periodontal or periodontal tissue containing the compound represented by Formula 1 or 2, a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient, or improving periodontitis. .
  • the present invention is a cosmetic composition containing a compound represented by the formula (1) or (2), a pharmaceutically acceptable salt thereof, or an optical isomer thereof as an active ingredient for use in promoting growth of the root or periodontal tissue, or improvement of periodontitis. It provides a use for.
  • the present inventors have found that when the tooth is embedded in agarose beads containing fargesin isolated from the extract, the root growth is remarkable, and alveolar bone is newly formed around the tooth.
  • the compound represented by Chemical Formula 1 or 2 may be usefully used as an active ingredient in quasi-drug compositions, cosmetic compositions or health functional foods for promoting growth of periodontal or periodontal tissues, or preventing or improving periodontitis. .
  • step 2) adding a mixed solvent of ethyl acetate and hexane to the methanol fraction of step 1) to obtain an eluate;
  • the extract is preferably extracted using water, C 1 ⁇ C 2 lower alcohol or a mixture thereof as a solvent, the mixed solvent of ethyl acetate and hexane of step 2) is 3: 7 or 5: 5 Preference is given to mixing in proportions.
  • Sinyi extracts, fractions and compounds used in the present invention were prepared by the following method.
  • Example ⁇ 1-1> The extract obtained in Example ⁇ 1-1> was partitioned into ethyl acetate and distilled water, and the distilled water layer was further fractionated with butanol, and the ethyl acetate layer was further fractionated with 90% methanol and nucleic acid.
  • the 90% methanol layer (21.17 g) was prepared using silica gel and 7 solvents of hexane and ethyl acetate (ethyl acetate: hexane) (1: 9, 2: 8, 3: 7, 5: 5, 100% ethyl). Acetate, 100% methanol).
  • the fargesin obtained in Example 1 was diluted in PBS (Dainippon Pharmaceuticals Inc., Japan) to a final concentration of 80 ⁇ m, and 4 agarose beads (Affi-Gel Blue Gel, # 153-7301, Bio-Rad Laboratories Inc., Japan) was washed with PBS and allowed to react for at least 60 minutes to allow fargesin to be absorbed into the beads. The other four beads were reacted only with PBS as a control. The molar was extracted from the lower jaws at the expense of a 5-day-old C57BL / 6 mouse (Sankyo Labo Service Corporation, Japan), and the extracted tooth was placed on agarose beads containing fargesin. Embedding.
  • the extracted tooth was embedded in agarose beads containing PBS.
  • Agarose beads were grafted into capsules of 8-week-old C57BL / 6 host mice (female, Sankyo Labo Service Corporation, Japan) kidneys, and host mice were bred at 12-hour light cycle, room temperature, and free feeding conditions. Three weeks after transplantation, the sacrifices were taken out and the teeth were observed. 3D images of the teeth were taken by micro CT (Rigaku R_mCT2).
  • the diol extract extracted in Example 1 was diluted in PBS to a concentration of 50, 500 ⁇ g / ml, and 4 agarose beads (Affi-Gel Blue Gel, # 153-7301, Bio-Rad Laboratories). Inc., Korea) was washed with PBS, and then allowed to react for at least 60 minutes to allow the sinus extract to be absorbed into the beads.
  • the other four beads were reacted only with PBS, and as in Comparative Example 1, the Fargesin compound was reacted with the beads.
  • molar was extracted from the lower jaws at the expense of a 5-day-old C57BL / 6 mouse (Dae Biolink, Korea), and the size of the extracted tooth was measured using agarose containing Fargesin or kidney extract. Embed in beads.
  • the extracted tooth was embedded in agarose beads containing PBS.
  • Agarose beads were grafted into capsules of 8-week-old C57BL / 6 host mice (female, Daehan Biolink, Korea) kidneys, and host mice were bred at 12-hour light cycle, room temperature and free feeding conditions. Three weeks later the sacrifice was taken out and the teeth were observed, and 3D images of the teeth were taken by micro CT.
  • the tablets were prepared by adding the above ingredients in the contents indicated, mixing them uniformly and pressing.
  • lactose and starch were mixed. Thereafter, the polysorbate was dissolved in pure water, and then an appropriate amount was added to the active ingredient, lactose and starch mixture, followed by atomization. After drying, the granules were granulated and then mixed with colloidal silicon dioxide and magnesium stearate. Tablets were prepared by pressing the granules.

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Abstract

La présente invention concerne une composition pharmaceutique contenant comme principe actif un extrait de fleur de Magnolia, une fraction de ce dernier, ou un composé représenté par la formule chimique suivante 1 ou 2. La fargésine, qui est isolée à partir de l'extrait de fleur de Magnolia et une fraction de ce dernier, favorise la croissance de la racine dentaire, favorise la croissance des tissus parodontaux par formation d'os alvéolaire autour de la dent, et a un effet d'inhibition de la parodontite. Par conséquent, la fargésine ainsi que l'extrait de fleur de Magnolia et la fraction de ce dernier la contenant peuvent être utilisés de façon efficace comme principe actif d'une composition pharmaceutique permettant la promotion de la croissance des racines dentaires et des tissus parodontaux, et pour la prévention et le traitement de la parodontite.
PCT/KR2016/011171 2015-10-07 2016-10-06 Composition pharmaceutique permettant de favoriser la croissance des tissus parondontaux, ainsi que la prévention et le traitement de la parondontite, contenant comme principe actif un extrait de fleur de magnolia, une fraction de ce dernier, ou un composé isolé à partir de ce dernier Ceased WO2017061781A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US15/766,605 US20180296623A1 (en) 2015-10-07 2016-10-06 Pharmaceutical composition for promoting periodontal tissue growth and for prevention and treatment of periodontitis, containing magnolia flower extract, fraction thereof or compound isolated therefrom as active ingredient
JP2018538509A JP6608071B2 (ja) 2015-10-07 2016-10-06 マグノリア花抽出物、その画分、またはそれらから単離された化合物を活性成分として含む、歯周組織の成長を促進するための、および歯周炎を予防および処置するための医薬組成物
CN201680071460.0A CN108367040A (zh) 2015-10-07 2016-10-06 包含木兰花提取物、其分离物、或从其中分离的化合物作为活性成分的用于促进牙周组织生长和用于牙周炎的预防和治疗的药物组合物
EP16853897.3A EP3360562A4 (fr) 2015-10-07 2016-10-06 Composition pharmaceutique permettant de favoriser la croissance des tissus parondontaux, ainsi que la prévention et le traitement de la parondontite, contenant comme principe actif un extrait defleur de magnolia

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KR20150140956 2015-10-07
KR10-2015-0140956 2015-10-07
KR1020160040438A KR101826229B1 (ko) 2015-10-07 2016-04-01 신이 추출물, 이의 분획물 또는 이로부터 분리한 화합물을 유효성분으로 함유하는 치주조직 성장 촉진, 및 치주염 예방 및 치료용 약학적 조성물
KR10-2016-0040438 2016-04-01

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JP2009114101A (ja) * 2007-11-05 2009-05-28 Kazuo Nagai 歯周病の予防又は治療用の医薬組成物、口腔衛生剤、並びに食品組成物
KR20130050967A (ko) * 2010-07-12 2013-05-16 가부시키가이샤 에리나 ａｘｉａｌ―ｅｑｕａｔｏｒｉａｌ ａｒｙｌ배향의 ｆｕｒｏｆｕｒａｎ형 리그난을 함유하는 골 형성 촉진용 약학적 조성물 및 이의 조성물을 포함하는 약학적 제제, 기능성 식품 및 건강 식품

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TWI668008B (zh) * 2017-09-07 2019-08-11 財團法人生物技術開發中心 木蘭萃取物、其製備方法及其用途

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