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WO2018155956A1 - Composition pharmaceutique, contenant un extrait de bulbe de lis, dans le traitement prophylactique ou thérapeutique d'un trouble cognitif - Google Patents

Composition pharmaceutique, contenant un extrait de bulbe de lis, dans le traitement prophylactique ou thérapeutique d'un trouble cognitif Download PDF

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Publication number
WO2018155956A1
WO2018155956A1 PCT/KR2018/002261 KR2018002261W WO2018155956A1 WO 2018155956 A1 WO2018155956 A1 WO 2018155956A1 KR 2018002261 W KR2018002261 W KR 2018002261W WO 2018155956 A1 WO2018155956 A1 WO 2018155956A1
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Prior art keywords
extract
lily
disease
dementia
composition
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Ceased
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PCT/KR2018/002261
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English (en)
Korean (ko)
Inventor
마진열
박희라
이희은
조원경
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Korea Institute of Oriental Medicine KIOM
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Korea Institute of Oriental Medicine KIOM
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Publication of WO2018155956A1 publication Critical patent/WO2018155956A1/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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • 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
    • 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 pharmaceutical composition for preventing or treating cognitive disorders.
  • a pharmaceutical composition for preventing or treating cognitive disorders comprising lily scale extract or a fraction thereof as an active ingredient
  • a method for preventing or treating cognitive disorders comprising administering the composition to a subject, lily scale extract Or functional health food composition for preventing or improving cognitive impairment, including fractions thereof as an active ingredient, lily scale extract or a functional food composition for improving memory or concentration comprising fractions thereof as an active ingredient, and lily scale extract or lily thereof
  • It relates to a composition for inducing neural stem cell proliferation comprising a fraction.
  • Lily means monocotyledonous lily and Lilium plant. It grows mostly in the shade of forests and trees or directly to the north where it is not exposed to direct sunlight. The leaves are rotated with their leaf sides displaced. The flowers are large, each tissue is divided into six branches, and there are wheat bulbs inside. There are 6 stamens and anther runs in T-shape. Capsules are flat seeds, and the lifespan of seeds is usually 3 years.
  • the lily is a root plant corresponding to the bulb, in particular, the lily is a root plant having a scaly structure among the roots.
  • the general root plant can be divided into scales, egg stems, tubers, root stems, tubers, the case of the lily is a plant corresponding to the double scales.
  • Lily scales which are the roots of the lilies, grow in the ground while the bases of the leaves are enlarged and have a layered scale structure.
  • the dementia patients also become a serious social problem, and the prevalence of dementia in Korea varies depending on the type and region of dementia.
  • the dementia is a symptom group, and as the disease progresses, cognitive impairment and dysfunction become more severe, and early diagnosis and early treatment are important.
  • Vascular dementia can prevent further progression if diagnosed and treated early, and Alzheimer's disease, which is a degenerative disease, Early detection and medication can delay the disease, so early detection and prevention are very important.
  • Patent Document 1 Korean Patent Application Publication No. 2016-0088165 relating to a composition for improving cognitive function or memory ability containing onion extract or a fraction thereof as an active ingredient.
  • Patent Document 2 Korean Patent Application Publication No. 2013-0107531 of the pharmaceutical composition for preventing and treating chronic obstructive pulmonary disease containing a lily extract as an active ingredient.
  • Patent Document 2 Korean Patent Application Publication No. 2013-0107531 of the pharmaceutical composition for preventing and treating chronic obstructive pulmonary disease containing a lily extract as an active ingredient.
  • the present inventors have made diligent research efforts to find a composition that improves cognitive function and learning ability.
  • the present invention has found that the lily scale extract has an effect of improving memory or concentration while preventing or treating cognitive impairment.
  • the lily scale extract has an effect of improving memory or concentration while preventing or treating cognitive impairment.
  • Still another object of the present invention is to provide a dietary supplement for preventing or improving cognitive impairment, comprising a lily scaly extract or a fraction thereof as an active ingredient.
  • Still another object of the present invention is to provide a health functional food composition for improving memory or concentration comprising lily scales extract or a fraction thereof as an active ingredient.
  • Still another object of the present invention is to provide an in vitro neural stem cell proliferation inducing composition comprising a lily scaly extract or a fraction thereof.
  • the pharmaceutical composition according to the present invention has a lily scale extract or a fraction thereof has the effect of preventing or treating cognitive impairment.
  • the lily scaly extract and its fractions have the effect of improving memory or concentration even when administered against a steady state without impaired brain cognitive function.
  • the lily scale extract or fractions thereof according to the present invention can be used in a method for preventing or treating cognitive impairment or in a dietary supplement for preventing or improving cognitive impairment.
  • it can be provided as a dietary supplement for improving memory or concentration.
  • FIG. 1 is a diagram showing a process of conducting an underwater maze experiment and a manual avoidance test for a test animal administered with a lily scale stem extract according to an embodiment of the present invention.
  • Figures 2a to 2d is a result of performing a labyrinth experiment on the experimental animals administered with the lily scale stem extract according to an embodiment of the present invention
  • Figures 2a and 2c is a hidden destination in the labyrinth experiment
  • 2b and 2d are graphs measuring the latency time taken by an experimental animal to find a destination by the underwater maze experiment (* is p ⁇ 0.05 compared to the normal group or the experimental group 1).
  • FIG. 2B is a graph measuring the latency time to reach platform in seconds.
  • each experimental group means:
  • Experimental group 2 the administration of scopolamine after the administration of donepezil (2mg / kg) to the normal group
  • Experimental group 4 The group administered the lily scale extract to the normal group by concentration (50, or 100 mg / kg) (no scoflavin administration).
  • Figure 3 is a manual evasion experiment on the experimental animals administered with lily scales extract according to an embodiment of the present invention (step-through latency time) in seconds (sec) It is a graph which shows the result of a measurement (* is p ⁇ 0.05 compared with normal group or the experimental group 1).
  • Figure 4 shows the result of confirming the number of BrdU target cells in the dentate gyrus of the hippocampus of the experimental animal brain after administration of the lily scale extract according to an embodiment of the present invention
  • (a) is BrdU target It is a photograph showing the staining result of the cells
  • (b) is a graph showing the result of quantitatively confirmed by confirming the number of BrdU target cells for each section (*) (* is p ⁇ 0.05 compared to normal group or experimental group 1).
  • Figure 5 is a photograph and graph showing the results of confirming the cell proliferation efficacy after 24 hours after treatment with lily scale extract according to an embodiment of the present invention NE-4C neural stem cell line, (a) is It is a photograph showing the results observed with an optical microscope, (b) is a graph showing the cell growth rate (* is p ⁇ 0.05 compared to 0 ⁇ g / ml).
  • Figure 6 shows the cell proliferation of the neuronal cell line due to the treatment of lily scale stem extract in NE-4C neural stem cell line according to an embodiment of the present invention through BrdU
  • (a) is a photograph showing the BrdU immunostaining results
  • (B) is a graph of BrdU incorporation assay (* is p ⁇ 0.05 vs. 0 ⁇ g / ml).
  • the inventors of the present invention in the course of making an effort to discover a substance that prevents or treats cognitive disorders such as forgetfulness, Alzheimer's disease, dementia, Parkinson's disease, Peak disease or Huntington's disease, It has also been found to improve memory or concentration.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of cognitive disorders comprising lily scale extract or a fraction thereof as an active ingredient.
  • the present invention provides a use for the prevention or treatment of cognitive impairment of a composition comprising a lily scale extract or a fraction thereof as an active ingredient.
  • the term “lilies scaly” of the present invention refers to a lily root of a lily, also called a diameter, and refers to a subterranean stem of a lily that is large in size and has dense leaves because it stores many nutrients around a short stem.
  • the lily scale is a concept that is distinguished from the ground including the flowers of the lily.
  • Cognitive function is the ability to use relevant information to adapt to the surrounding environment, such as perception, memory, learning, attention, vigilance, understanding, and interpretation. Means.
  • the composition of the present invention can exhibit an excellent effect on cognitive function, specifically learning and memory.
  • cognitive impairment is a concept that includes a condition resulting from a decrease in cognitive function, a disease according to it, and all diseases in which the symptom is a symptom, and may preferably mean a disorder caused by damage to brain neurons.
  • the cognitive dysfunction may mean any one or more degenerative brain diseases selected from the group consisting of forgetfulness, Alzheimer's disease, dementia, Parkinson's disease, peak disease, Creutzfeldt-Jakob disease, Huntington's disease, ischemic stroke, and hemorrhagic stroke. Can be.
  • Dementia is a syndrome in which the cognitive function of various areas such as memory, language, and judgment are reduced, and thus cannot perform daily life properly.Dementia is a brain function that is damaged by various causes. As a result, the overall decline may result in significant disruption in daily life.
  • the dementia can be divided into dozens of causative diseases, but among them, Alzheimer's disease is the most common cause and exceeds 50%.
  • the dementia may be selected from the group consisting of vascular dementia, Alzheimer's dementia, Louis dementia, dementia caused by head trauma, dementia caused by brain tumor, and dementia caused by metabolic disease.
  • the route to the destination is also simplified, and the time is significantly reduced (FIGS. 2A and 2B).
  • the route to the destination is also simplified, and the time is significantly reduced (FIGS. 2A and 2B).
  • the oral administration of lily scale extract to the animal model induced brain cognitive impairment in the same way manual evasion experiments showed that the latency time was restored to normal compared to the animal model with brain impaired cognitive impairment. (FIG. 3A).
  • the BrdU staining administration of the lily scale extract it was confirmed that the number of BrdU target cells significantly increased compared to the other case (Fig. 4).
  • extract of the present invention means an extract obtained by extracting the lily scales or their pulverized products, a dilution or concentrate of the extract, a dried product obtained by drying the extract, a crude product or a purified product of the extract, or these And extracts of all formulations that can be formed using the extract itself and the extract, such as mixtures thereof.
  • the method of extracting the lily scales is not particularly limited as long as an extract showing an effect of preventing or treating cognitive impairment can be obtained, and may be extracted according to a method commonly used in the art.
  • the type of extraction solvent used to extract the lily scales in the present invention is not particularly limited as long as an extract showing an effect of preventing or treating cognitive impairment can be obtained, and any solvent known in the art may be used. Can be used.
  • the extraction solvent may be used alone or in combination of one or more kinds of water, alcohol, etc.
  • the extraction solvent may be alone or one or more kinds of water or alcohol having 1 to 6 carbon atoms. Mixing may be used, and as another example, the extraction solvent may be water.
  • fraction of the present invention means the result obtained by performing the fractionation to separate a specific component or a specific component group from a mixture comprising various various components.
  • the fraction may be the result of fractionation of the lily scale extract by various methods such as solvent fractionation, ultrafiltration fractionation, chromatography fractionation.
  • the method for obtaining the fraction is also not particularly limited as long as it can obtain a fraction exhibiting the effect of preventing or treating cognitive impairment, and may be performed according to a method commonly used in the art. As an example, a method of obtaining a fraction from a lily scaly hydrothermal extract using solvent fractionation may be used.
  • the kind of the fractionation solvent used to obtain the fraction in the present invention is also not particularly limited as long as it can obtain a fraction showing the effect of preventing or treating cognitive impairment, and is carried out according to a method commonly used in the art.
  • the fractionating solvent may be a polar solvent such as water or alcohol;
  • Non-polar solvents such as hexane, ethyl acetate, chloroform and dichloromethane may be used alone or in combination of one or more thereof.
  • prevention means any action that inhibits or delays cognitive impairment by administering the composition of the invention to a subject.
  • treatment refers to any action by which the composition of the present invention is administered to a subject to improve or benefit from cognitive impairment.
  • composition of the present invention may be prepared in the form of a pharmaceutical composition for preventing or treating cognitive disorders further comprising a suitable carrier, excipient or diluent commonly used in the manufacture of pharmaceutical compositions.
  • the carrier may be an unnatural carrier.
  • the pharmaceutical composition may be formulated in the form of oral dosage forms, external preparations, suppositories, and sterile injectable solutions, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, respectively, according to conventional methods. Can be.
  • carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate , Calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, It may be prepared by mixing sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium styrate and talc may also be used.
  • Liquid preparations for oral use may include various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc., in addition to water and liquid paraffin, which are simple diluents commonly used in suspensions, solutions, emulsions, and syrups. have.
  • Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories.
  • non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used.
  • As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • the content of the lily scale extract or its fraction contained in the pharmaceutical composition of the present invention is not particularly limited, but is based on the total weight of the final composition of 0.0001 to 50% by weight, more preferably 0.01 to 20% by weight May be included.
  • the pharmaceutical composition of the present invention may be administered in a pharmaceutically effective amount
  • Sufficient amount means an effective dose level means the severity of the disease, the activity of the drug, the age, weight, health, sex, sensitivity of the patient to the drug, the time of administration of the composition of the invention used, the route of administration and the rate of excretion treatment Period of time, factors including drugs used in combination or coincidental with the compositions of the invention used, and other factors well known in the medical arts.
  • the pharmaceutical composition of the present invention may be administered alone or in combination with known cognitive disorder therapeutics. In consideration of all the above factors, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects.
  • the dosage of the pharmaceutical composition of the present invention can be determined by those skilled in the art in consideration of the purpose of use, the degree of addiction of the disease, the age, weight, sex, history, or type of substance used as an active ingredient of the patient.
  • the pharmaceutical composition of the present invention may be administered at about 0.1 ng to about 100 mg / kg, preferably 1 ng to about 10 mg / kg, per adult, and the frequency of administration of the composition of the present invention is specifically Although not limited, it can be administered once a day or several times in divided doses.
  • the dosage does not limit the scope of the invention in any aspect.
  • the concentration of the lily scale extract or fractions thereof in the composition may be 5 to 200 ⁇ g / ml, more specifically 50 to 200 ⁇ g / ml.
  • a method of preventing or treating a cognitive impairment comprising administering a pharmaceutical composition to a subject having or likely to develop a cognitive impairment.
  • the term "individual” of the present invention may include without limitation mammals, farmed fish, etc., which may cause cognitive impairment or cause blood glucose abnormalities such as mice, livestock, and the like.
  • the term "administration" means introducing the pharmaceutical composition of the present invention to a subject having suspicion of rhinitis by any suitable method, and the route of administration of the pharmaceutical composition for preventing or treating cognitive disorders of the present invention may be administered through any general route. May be administered.
  • the pharmaceutical composition of the present invention is not particularly limited to this, but as desired, routes of intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, intranasal administration, pulmonary administration, rectal administration, etc. It can be administered through.
  • the oral composition when orally administered, the lily scaly extract or a fraction thereof may be denatured by gastric acid, so the oral composition should be formulated to coat the active agent or to protect it from degradation in the stomach.
  • the composition may be administered by any device in which the active substance may migrate to the target cell.
  • the present invention provides a dietary supplement for preventing or improving cognitive impairment, comprising a lily scale extract or a fraction thereof as an active ingredient.
  • the lily scale Since the lily scale has been used for a long time as a natural substance has proven its stability, it can be prepared and consumed in the form of a food that can prevent or improve cognitive impairment.
  • the term "improvement” means any action that at least reduces the parameters associated with the condition, e.g., the degree of symptoms, treated with the administration of a composition comprising a lily scaly extract of the present invention or a fraction thereof.
  • the health functional food 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 salts thereof, Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. Others may contain pulp for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components can be used independently or in combination.
  • the health functional food is any one of meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, drink, alcoholic beverage and vitamin complex Can be.
  • the health functional food may further include food additives, and the suitability as a "food additive" is related to the relevant items according to the General Regulations and General Test Act of the Food Additives Code approved by the Food and Drug Administration unless otherwise specified. Judging by the standards and standards.
  • Items listed in the "Food Additives Code” include, for example, chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, cinnamon acid, natural additives such as dark blue, licorice extract, crystalline cellulose, high-lower pigment, guar gum, L Mixed preparations, such as sodium glutamate preparation, a cotton addition alkali preparation, a preservative preparation, and a tar pigment preparation, are mentioned.
  • chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, cinnamon acid, natural additives such as dark blue, licorice extract, crystalline cellulose, high-lower pigment, guar gum, L Mixed preparations, such as sodium glutamate preparation, a cotton addition alkali preparation, a preservative preparation, and a tar pigment preparation, are mentioned.
  • composition to be added to food including beverages in the process of manufacturing a health functional food may be appropriately added or subtracted as needed, specifically, may be added to include 1 to 15% by weight in 100% by weight of food. .
  • a health functional food composition for improving memory or concentration comprising lily scale extract or a fraction thereof as an active ingredient.
  • the "health functional food” or “improvement” is as described above.
  • the term “memory” means the ability to store or preserve memory transmitted to the brain before external or internal damage occurs to the brain.
  • concentration means a memory or learning ability that rises to a short term maximum.
  • the time for finding the destination is shorter than the normal group ( 2c and 2d).
  • the passive avoidance experiment conducted by administering only the lily scale extract in the normal state it was confirmed that the latency time was significantly increased than that of the normal group (FIG. 3B), and the lily scale extract improved memory and maintained memory. It can be confirmed that it is effective in.
  • composition for inducing in-vitro neural stem cell proliferation comprising a lily scale extract or a fraction thereof.
  • the lily scale extract induces the proliferation of the NE-4C neural stem cell line (FIG. 5), and NE-4C through BrdU immunostaining. Neuronal cell line proliferation effect can be confirmed (FIG. 6).
  • the anticholinergic substance scopolamine was intraperitoneally injected at a concentration of 1 mg / kg for 2 weeks to prepare a memory-inhibited animal model.
  • the extract prepared in Example 1 was orally administered for 2 weeks at a concentration of 50, 100 mg / kg daily for 2 hours before scopolamine administration.
  • Donepezil hydrochloride a treatment for cholinesterase inhibitors of Alzheimer's disease, was orally administered at a concentration of 2 mg / kg.
  • Experimental group 2 the administration of scopolamine after the administration of donepezil (2mg / kg) to the normal group
  • Experimental group 4 The group administered the lily scale extract to the normal group by concentration (50, or 100 mg / kg) (no scoflavin administration).
  • mice were sacrificed by perfusion fixation through the heart for histological examination after 2 weeks of administration, and brains were harvested. In addition, some mice underwent underwater maze experiments and passive avoidance tests for behavioral examination two weeks after the last dose. The process is shown in FIG.
  • the Morris water maze test is a method of testing spatial learning and memory to measure the time it takes to find a hidden platform after a mouse is dropped into a tank filled with water. Experimental animals with better learning and memory have shorter time to find hidden platforms.
  • the experimental animals of each experimental group were randomly placed in four directions in a pool having a circular hidden platform, and the experiment was performed to find the hidden platform. Experimental animals were to stay on the platform for about 5 seconds when escaping the hidden platform within 60 seconds. If the test animal could not find the platform within 60 seconds, the experimenter guided it and left it on the platform for 10 seconds to finish the test.
  • the motivation for visiting the platform was to escape from the water and collected the experimental results through the image tracking system. The experiment was conducted continuously for 6 days in total, three times a day.
  • Figures 2a and 2c is a schematic diagram showing the path to the experimental animal to find the hidden destination (platform) through the underwater maze experiment
  • Figures 2b and 2d is a graph measuring the time taken to find the destination (platform).
  • experimental group 1 induced brain cognitive impairment by scopolamine it was confirmed that the path to the hidden destination is confused, it takes a long time to find the destination.
  • experimental group 3 which was administered with the lily scale extract, was able to confirm that the route to the destination was simplified, and the time was significantly shortened.
  • Figure 3 shows the time (latency time) measured according to the above experiment, specifically (a) of Figure 3 (a) passive avoidance test results of experimental animals administered with Donepezil or lily scale extract to the memory model of inhibition (B) shows the results of passive avoidance of experimental animals administered with lily scale extract to normal group.
  • the dentate gyrus of the hippocampus is known as a site for hippocampal neurogenesis, in which new neurons are generated throughout life as well as learning and memory.
  • euthanasia was performed to confirm the survival (cell survival study) of newly formed cells in the hippocampus of the brain at 2 weeks after intraperitoneal injection of BrdU for 6 days at 100 mg / kg. I was.
  • BrdU is a marker that can replace thymidine in the S phase where DNA replication takes place and can target newly proliferating cells.
  • the number of BrdU target cells (the number of newly formed cells) in the dentate gyrus of the brain was confirmed.
  • the brain extracted in Experimental Example 1 was sliced into 1-in-6 series in cryostat.
  • DNA was denatured by treatment with 0.6% hydrogen peroxide and exposing the brain tissue sections in the order of heating, acid, and base. After washing, the cells were blocked and then reacted with an anti-rat BrdU antibody at 4 ° C. overnight, followed by 3 hours of reaction with a biotinylated anti-rat secondary antibody at room temperature. After washing, the solution was reacted with ABC solution for 1 hour at room temperature, and then stained with DAB kit and observed under an optical microscope. The 6th-10th sections of the rostro-caudal sections of the whole hippocampus were examined. After measuring the total number of BrdU target cells in the dentate gyrus of each hippocampus, samples were calculated by fractions to quantify the number of newly formed cells in the hippocampus. The researcher has improved the accuracy of the experiment.
  • BrdU staining results according to the experiment (a) and the statistical results (b) are shown in Figure 4.
  • experimental group 1 administered scopolamine the number of BrdU target cells decreased compared to the normal group, indicating that survival of newly formed cells in the hippocampus of the hippocampus was reduced.
  • experimental group 3 to which the lily scale extract was administered before the scopolamine administration the number of BrdU target cells was significantly increased compared to the experimental group 1.
  • experimental group 4 was found to increase the number of BrdU target cells, especially in the 50mg / kg, 100mg / kg increased the survival of the newly formed cells in the dentate gyrus of the hippocampus compared to the normal group, which is also the lily scales for the normal group This means that the extract has an effect of increasing the hippocampal nerve stem cells and hippocampal nerve regeneration.
  • NE-4C neural stem cell line derived from cranial neural germ layers (NE-4C neural stem cell line) was treated with the concentration of the lily scale extract prepared in Example 1, 0.25 mg / ml to the cells 24 hours after treatment A concentration of MTT solution was added and incubated for another 2 hours. Then, the formazan precipitate was dissolved in dimethyl sulfoxide (DMSO), and then the absorbance was measured at 560 nm with a microplate reader (SpectraMax i3, Molecular devices, CA, USA).
  • DMSO dimethyl sulfoxide
  • the extract of the scales of the lily of the stem was confirmed the cell proliferation-inducing effect, especially at a concentration of 50 to 200 ⁇ g / ml cell growth rate of about 1.5 compared to the control (0 ⁇ g / ml) It was confirmed that the fold improved.

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Abstract

La présente invention concerne : une composition, contenant un extrait de bulbe de lis ou une fraction de celui-ci en tant que principe actif, dans le traitement prophylactique ou thérapeutique d'un trouble cognitif ; une composition d'alicament, contenant un extrait de bulbe de lis ou une fraction de celui-ci en tant que principe actif, pour améliorer la mémoire ou la concentration ; et une composition, contenant un extrait d'ampoule de lis ou une fraction de celui-ci, pour induire la prolifération de cellules souches neurales in vitro.
PCT/KR2018/002261 2017-02-24 2018-02-23 Composition pharmaceutique, contenant un extrait de bulbe de lis, dans le traitement prophylactique ou thérapeutique d'un trouble cognitif Ceased WO2018155956A1 (fr)

Applications Claiming Priority (2)

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KR1020170025092A KR20180098459A (ko) 2017-02-24 2017-02-24 백합 비늘줄기 추출물을 포함하는 인지장애의 예방 또는 치료용 약학 조성물
KR10-2017-0025092 2017-02-24

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WO2018155956A1 true WO2018155956A1 (fr) 2018-08-30

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