WO2017213306A1 - 머위 잎 추출물을 포함하는 기억력 개선용 조성물 - Google Patents

머위 잎 추출물을 포함하는 기억력 개선용 조성물 Download PDF

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Publication number
WO2017213306A1
WO2017213306A1 PCT/KR2016/012051 KR2016012051W WO2017213306A1 WO 2017213306 A1 WO2017213306 A1 WO 2017213306A1 KR 2016012051 W KR2016012051 W KR 2016012051W WO 2017213306 A1 WO2017213306 A1 WO 2017213306A1
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Prior art keywords
acid
leaf extract
extract
memory
butterbur
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PCT/KR2016/012051
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English (en)
French (fr)
Korean (ko)
Inventor
오명숙
김민산
우경완
박상수
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주식회사 네이처바이오
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Priority to JP2018534843A priority Critical patent/JP6735347B2/ja
Priority to CN201680076348.6A priority patent/CN108472325B/zh
Publication of WO2017213306A1 publication Critical patent/WO2017213306A1/ko

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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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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 COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • 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
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function

Definitions

  • the present invention relates to a method for preparing coltsfoot leaf extract having a memory improving effect and a composition for improving memory including coltsfoot leaf extract.
  • An object of the present invention (a) extracting by adding water to the coltsfoot leaves; (b) freeze drying the butterbur leaf extract; (c) adding ethanol to the freeze-dried product of the coltsfoot leaf extract and then precipitating; And (d) removing the supernatant of the precipitate and lyophilizing the precipitate.
  • the present invention to achieve the above object, (a) extract by adding water to the butterbur leaves; (b) freeze drying the butterbur leaf extract; (c) adding ethanol to the freeze-dried product of the coltsfoot leaf extract and then precipitating; And (d) removing the supernatant of the precipitate and freeze drying the precipitate.
  • Ethanol in the step (c) is characterized in that 50 to 80% ethanol, characterized in that the precipitate for 20 to 30 hours at room temperature.
  • the butterbur leaf extract has a memory improving ability, 3,5-di-O-caffeoylquinic acid (3,5-di-O-caffeoylquinic acid), 4,5-di-O-caffeoylquinic acid (4,5-di-O-cafeoylquinic acid), 3,4-di-O-caffeoylquinic acid (3,4-di-O-cafeoylquinic acid) and 6,7-dihydroxy-4- ( 3,4-dihydroxyphenyl) naphthalene-2-carboxylic acid (6,7-dihydroxy-4- (3,4-dihydroxyphenyl) naphthalene-2-carboxylic acid) containing a component selected from the group consisting of It can be characterized.
  • the present invention also provides a pharmaceutical composition for improving memory and health functional food comprising the extract of coltsfoot leaf obtained by the above method.
  • the pharmaceutical composition is characterized in that it has a protective and regenerative effect of neurons, and may be administered orally, subcutaneously, intravenously, intramuscularly, intranasally or intraperitoneally, and may be tablets, capsules, granules, It may be characterized in that it is prepared in the form of pills, syrups, solutions, emulsions, suspensions or injections.
  • the health functional food is characterized in that it has a protective and regenerative effect of nerve cells, further comprising one or more of carriers, diluents, excipients and additives, tablets, pills, powders, granules, powders, capsules and liquids It may be characterized in that it is formulated in one formulation selected from the group consisting of formulations.
  • the pharmaceutical composition or dietary supplement is 3,5-di-O-caffeoylquinic acid (3,5-di-O-caffeoylquinic acid), 4,5-di-O-caffeoylquinic acid (4 , 5-di-O-cafeoylquinic acid), 3,4-di-O-caffeoylquinic acid (3,4-di-O-cafeoylquinic acid) and 6,7-dihydroxy-4- (3,4 -dihydroxyphenyl) naphthalene-2-carboxylic acid (6,7-dihydroxy-4- (3,4-dihydroxyphenyl) naphthalene-2-carboxylic acid) to include a component selected from the group consisting of Can be.
  • Butter leaf extract through conventional water extraction or alcohol extraction has a limit in extracting only the components that effectively extract neurons to extract the various components of the coltsfoot leaves.
  • the step of water extraction, freeze-drying, ethanol extraction step sequential step, by effectively removing the unnecessary components of the coltsfoot leaf and recover only useful components coltsfoot leaves showing the neuronal cell protective effect An extract can be obtained.
  • the health functional food for improving memory further comprises one or more of a carrier, a diluent, an excipient and an additive, and is formulated as one selected from the group consisting of tablets, pills, powders, granules, powders, capsules and liquid formulations. It features. Foods to which the extract of the present invention can be added include various foods, powders, granules, tablets, capsules, syrups, beverages, gums, teas, vitamin complexes, and health functional foods.
  • additives that may be further included in the present invention, natural carbohydrates, flavors, nutrients, vitamins, minerals (electrolytes), flavors (synthetic flavors, natural flavors, etc.), colorants, fillers (cheese, chocolate, etc.), One or more components selected from the group consisting of fact acids and salts thereof, alginic acids and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonating agents and pulp .
  • natural carbohydrates examples include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
  • the composition according to the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like.
  • the composition according to the present invention may contain fruit flesh for the production of natural fruit juices and vegetable drinks. These components can be used independently or in combination.
  • carrier examples include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, erythritol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium phosphate, calcium Silicates, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water, sugar syrup, methylcellulose, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate And at least one selected from the group consisting of mineral oils.
  • a health functional food for improving memory is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. that are commonly used.
  • the content of the extract according to the present invention as an active ingredient in the above-described formulations can be appropriately adjusted according to the use form and purpose, patient condition, type of symptom and severity, etc., based on the solid content weight, 0.001 to 99.9% by weight, preferably 0.01 to 50% by weight, but is not limited thereto.
  • Butterbur (common name: Butterbur or scientific name: Petasites japonicus) is a perennial shrub found not only in Europe but also in parts of Asia and North America. Extracts isolated from the roots and leaves of coltsfoot have been used as therapeutics for over 2,000 years.
  • butterbur extract has been reported to be used primarily for muscle relaxation, to treat conditions such as abdominal pain in the stomach, to spasms of smooth muscle, to reduce pain and to be used for headaches (Eaton J., Townsend Lett, 2000, 202, 104-106). Butterbur has also been reported to have therapeutic effects on asthma and allergic diseases (Thomet OA, Simon HU, Int Arch Allergy Immunol, 2002, 129 (2), 108-12).
  • Butterbur leaf extract obtained by the production method according to the invention shows an excellent effect on the protection and regeneration of nerve cells.
  • Figure 1 shows the cell viability according to the coltsfoot leaf extract.
  • Figure 2 shows the cytotoxicity results according to the concentration-specific administration of KP-1.
  • Figure 3 shows the neuronal cell protection effect according to the concentration-specific administration of KP-1.
  • Figure 5 shows the cell viability of secondary isolates f3-f11 of KP-1.
  • Figure 6 confirms the effect of improving memory according to the concentration-specific administration of KP-1.
  • Figure 7 is to observe whether the hippocampal tissue tissue damage and recovery of the experimental rats.
  • Figure 8 confirms the tissue regeneration and protective effect of hippocampal tissue according to the concentration of KP-1 administration.
  • Figure 9 confirms that the neuronal protective effect does not appear in simple water extraction, ethanol extraction.
  • HT22 cells which are the tissues of hippocampus that control memory, were cultured in DMEM medium containing 10% FBS (heat-inactive) and 1% PS in 96 well cell culture plates (1 ⁇ 10 4 cell / well) for 24 hours. Treat only samples (cytotoxic) or treat samples and A ⁇ toxicity (neuroprotective efficacy) and incubate at 37 ° C for 12 hours before 3- (4,5-Dimethylthiazol-2-yl) -2,5-Diphenyltetrazolium Bromide (MTT ) And the reaction was carried out for 2 hours, and the absorbance at 570 nm was measured and evaluated.
  • FBS heat-inactive
  • PS 96 well cell culture plates
  • KP-1F4 In order to search for an active ingredient of KP-1, KP-1 was separated into F1-F8 using resin DIAION HP-20, and F4 showing the highest cell viability was named KP-1F4 (FIG. 4). KP-1F4 was secondary separated to f1-f11 with SEPHADEX LH2. As a result, f1 and f2 showed no activity in preliminary experiments, and showed cell viability of 75% or more in f9 and f11 (FIG. 5). f9 and f11 were purified by LC-MASS and NMR, and the components of f9 were identified by the following Chemical Formulas 1 to 3 and the components of f11 by the following Chemical Formula 4:
  • ICR male, 7 weeks old was used for 1 week after acclimatization and breeding.
  • the breeding environment of this experiment was temperature 20-24 °C, relative humidity 50-60%, ventilation 15 times / h, lighting time light & dark system 12 hours (07: 00-19: 00), illuminance 150-200 Lux. Breeding in the set place, the solid feed and water for the mouse was allowed to intake freely. The animal was bred according to the animal breeding regulations of Kyung Hee University in compliance with the standards set forth by the National Institutes of Health (NIH) (No. 86-23, revised 1985).
  • NASH National Institutes of Health

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PCT/KR2016/012051 2016-06-08 2016-10-26 머위 잎 추출물을 포함하는 기억력 개선용 조성물 WO2017213306A1 (ko)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2018534843A JP6735347B2 (ja) 2016-06-08 2016-10-26 フキの葉抽出物を含む記憶力改善用組成物
CN201680076348.6A CN108472325B (zh) 2016-06-08 2016-10-26 包含蜂斗菜叶提取物的用于改善记忆力的组合物

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KR1020160070868A KR101689656B1 (ko) 2016-06-08 2016-06-08 머위 잎 추출물을 포함하는 기억력 개선용 조성물
KR10-2016-0070868 2016-06-08

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KR101895430B1 (ko) * 2017-08-02 2018-09-06 주식회사 네이처바이오 머위 잎으로부터 푸키놀릭산을 분리하는 방법
CL2018002863A1 (es) * 2018-10-08 2019-03-29 Rubisco Biotechnology Extracto acuosos a partir de células de fitzroya cupressoides (alerce) con propiedades antienvejecimiento y en la regeneración de la piel
KR102386936B1 (ko) * 2020-01-15 2022-04-13 한국수목원정원관리원 머위 추출물을 유효성분으로 함유하는 패혈증 예방, 개선 또는 치료용 조성물
KR102303624B1 (ko) * 2020-01-22 2021-09-16 한국식품연구원 머위잎 추출물을 유효성분으로 포함하는 근육 질환 예방, 개선 또는 치료용 조성물

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CN108472325A (zh) 2018-08-31
KR101689656B1 (ko) 2016-12-26
CN108472325B (zh) 2021-08-17
JP6735347B2 (ja) 2020-08-05

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