WO2020050462A1 - Composition de protection des neurones comprenant un dérivé de naphtopyrone dérivé de pousses de cassia obtusifolia - Google Patents

Composition de protection des neurones comprenant un dérivé de naphtopyrone dérivé de pousses de cassia obtusifolia Download PDF

Info

Publication number
WO2020050462A1
WO2020050462A1 PCT/KR2019/000399 KR2019000399W WO2020050462A1 WO 2020050462 A1 WO2020050462 A1 WO 2020050462A1 KR 2019000399 W KR2019000399 W KR 2019000399W WO 2020050462 A1 WO2020050462 A1 WO 2020050462A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
naphthopyrone
extract
composition
group
Prior art date
Application number
PCT/KR2019/000399
Other languages
English (en)
Korean (ko)
Inventor
권학철
박진수
권재영
황호성
이정환
이재욱
김동회
김형석
장성율
정상훈
Original Assignee
한국과학기술연구원
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
Application filed by 한국과학기술연구원 filed Critical 한국과학기술연구원
Priority to CN201980072747.9A priority Critical patent/CN112996799A/zh
Publication of WO2020050462A1 publication Critical patent/WO2020050462A1/fr

Links

Images

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/613—Unsaturated compounds containing a keto groups being part of a ring polycyclic
    • C07C49/617—Unsaturated compounds containing a keto groups being part of a ring polycyclic a keto group being part of a condensed ring system
    • C07C49/643—Unsaturated compounds containing a keto groups being part of a ring polycyclic a keto group being part of a condensed ring system having three rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/06—Separation; Purification
    • C07H1/08—Separation; Purification from natural products
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0621—Eye cells, e.g. cornea, iris pigmented cells
    • 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
    • A23V2300/00—Processes
    • A23V2300/14—Extraction
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/999—Small molecules not provided for elsewhere

Definitions

  • the present specification relates to a composition
  • a composition comprising a naphthopyrone derivative and a shoot sprout extract comprising the same as an active ingredient.
  • the hippocampus is a structure of the medial temporal lobe of the brain and plays an important role in the cognitive function of humans and animals.
  • the hippocampus is known to be vulnerable to physiological and oxidative stress stimuli and to be a central tissue for cognitive impairment caused by stress. Stress can cause hippocampal structure and brain cell production, synaptic plasticity, and behavioral changes related to the hippocampus (Eunjoo Kim, Journal of the Korean Psychological Association: Cognitive and Biology, 2012, 24, 65-88).
  • ischemic nerve damage When oxidative stress in neurons is induced in the hippocampus, pituitary gland, striatum, black matter, the whole cortex, or the hypothalamus, neuronal cell death increases and neurons and growth factors decrease, resulting in amyotrophic lateral sclerosis (ALS), Parkinson's disease, or brain It is known to cause acute or chronic neurological diseases such as ischemic nerve damage (Rahman, T. et al. Adv. Biosci. Biotechnol. 2012, 3, 997-1019).
  • the number of patients with retinal disease has increased by about 8% per year from about 830,000 in 2010 to about 12.5 million in 2015.
  • the retina is the thinner nerve film inside the eye that is likened to the film of a camera.
  • Over 100 million photoreceptor cells (light-sensing cells) and over 1 million optic nerve cells are present in the retina, converting light into electrical signals and transmitting the image of the object through the nerve to the brain. If the nerves in the retina are damaged or nerve function is abnormal, vision and vision problems may occur.
  • Representative retinal diseases include diabetic retinopathy, age-related macular degeneration, retinal pigmentary degeneration, retinal detachment and retinal vascular obstruction, including decreased vision, blurred vision and blindness.
  • Glaucoma is a typical eye disease in which retinal optic nerve damage occurs, and the optic nerve is damaged due to increased intraocular pressure, ischemia and oxidative stress (Kim, NY et al. J. Korean Opthalmol. Soc. 2015, 56, 70-79; Kang, JH et al. J. Korean Ophthalmol. Soc. 2003, 44, 965-970; Lee, SM et al. J. Korean Ophthalmol. Soc. 2002, 43, 2577-2584).
  • Glutamate is an excitatory neurotransmitter that plays an important role in the central nervous system of vertebrates. Glutamate is involved in the expression of various physiological functions by acting on quisqualate receptors, NMDA (N-methyl-D-aspartate) receptors, and Kainite receptors, which are concentrated in the cerebellar amygdala and hippocampus, which are known to be involved in memory and learning in brain tissues. .
  • quisqualate receptors quisqualate receptors
  • NMDA N-methyl-D-aspartate
  • Kainite receptors which are concentrated in the cerebellar amygdala and hippocampus, which are known to be involved in memory and learning in brain tissues.
  • glutamate increases in the outside of neurons and the concentration of glutamate outside the cell increases rapidly, it can act as an oxidative neurotoxic substance (Hyun-Jeong Kim et al., J. Life Sci. 2009, 19, 963-967).
  • Excessive glutamate is known to be associated with various acute neurological disorders, including anemia, oxygen deficiency, hypoglycemia, trauma, and several chronic degenerative neurological disorders. Glutamate in the eye has been implicated in acute disorders and death of retinal ganglion cells (Otori, Y. et al. Invest. Ophthalmol. Vis. Sci. 1998, 39, 972-981). It is known that overproduction of reactive oxygen species (ROS) is stimulated by the production of a large amount of glutamate and presynaptic glutamate receptor activation (Tarasenko A. et al. Neurochem. Int. 2012, 61, 1044 -1051).
  • ROS reactive oxygen species
  • ROS Reactive Oxygen Species
  • ROS Since ROS is chemically unstable and highly reactive, it can react with lipids, nucleic acids, and proteins in vivo to cause DNA damage, increase the concentration of free calcium and iron in the cell, and damage the ion transport system of the biofilm (Kiselyov, K. et al. Cell Calcium. 2016, 60, 108-114). In addition, ROS is also known to induce light-induced damage to the optic nerve by generating light (Masuda, T. et al. Oxid.Med. Cell. Longevity. 2017; article ID 9208489, 14 pages).
  • the deficiency has traditionally been used for eye health and is known to have excellent antioxidant activity. It is a mature seed of the herbaceous plant belonging to the legume (Cassia obtusifolia L.) or Ginjiang Namcha (Cassia tora L.). It is cultivated in all parts of Korea and glossed in a bow-shaped pod that is about 10 cm after the leaves are cut. Seeds containing a single line (Yen, G.-C. et al. J. Agric. Food Chem. 1998, 46, 820-824). The extract of terminator has been studied and reported for improving diabetes, dyslipidemia, liver protection, antibacterial, and hypotensive effects (Dong, X. et al. Mol. Med. Rep. 2017, 16, 2331-2346).
  • the shoot sprout extract produced a new antioxidant component compared to the extract from the shooter, increasing the antioxidant active ingredient and significantly increasing it.
  • the present inventors have confirmed that the antioxidant activity and neuronal cell protective action, and naphtopyron component including the novel compound 7-hydroxymusininyl- lubrofusarin-8'-O-glucoside isolated from the shoot sprout extract.
  • the present invention has been completed by confirming that they exhibit the effect of protecting retinal neurons and hippocampal neurons from glutamate induced oxidative stress.
  • Patent Document 1 KR 10-1503429 B1
  • Patent Document 2 KR 10-2010-0082054 A
  • Patent Document 3 KR 10-0877371 B1
  • Patent Document 4 KR 10-1807367 B1
  • Patent Document 5 KR 10-2016-0058613 A
  • Non-Patent Document 1 Jung, H. A. Journal of Ethnopharmacology, 2016, vol 191, 152-160; Inhibitory activities of major anthraquinones and other constituents from Cassia obtusifolia against ⁇ -secretase and cholinesterases.
  • Non-patent document 2 Shrestha, S. et al. Archives Pharmacal Research, 2018, online publication https://doi.org/10.1007/s12272-018-1044-0; Two new naphthalenic lactone glycosides from Cassia obtusifolia L. seeds.
  • Another object of the present specification is to provide a composition that exhibits an effect of protecting neuronal cell damage from oxidative stress or inhibiting neuronal cell death.
  • Still another object of the present specification is to provide a composition that exhibits a prophylactic or therapeutic effect of a neurological damaging disease caused by damage or death of retinal nerve cells or hippocampal nerve cells.
  • Another object of the present specification is to provide a composition that exhibits an antioxidant effect.
  • the present invention provides a naphthopyrone derivative of Formula 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
  • the present invention provides one or more naphthopyrone derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvents thereof selected from the group consisting of naphthopyrone derivatives of the following Chemical Formulas 1 to 5 Provides a method of manufacturing the cargo.
  • the present invention is one or more naphthopyron derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or the like selected from the group consisting of naphthopyrone derivatives of Formula 1 to Formula 5.
  • the present invention is one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or One or more selected from the group consisting of solvates, Cassia obtusifolia L. or Cassia tora L. bud extract, or a fraction of the bud containing it as an active ingredient, comprising retinal nerve cells or hippocampal nerve cells.
  • a composition for the prevention or treatment of a neuro-damaging disease caused by damage or death is provided.
  • the present invention is one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5, stereoisomers thereof, pharmaceutically acceptable salts, hydrates thereof, or It provides at least one selected from the group consisting of solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extract, or a bud fraction containing the same as an active ingredient, provides an antioxidant composition.
  • the composition according to an aspect of the present invention has an antioxidant effect and an effect of protecting nerve cells from oxidative stress or inhibiting apoptosis, and in particular, damage or death of retinal nerve cells or hippocampal nerve cells due to glutamate toxicity. It has an inhibitory effect. Therefore, the composition according to one aspect of the present invention can be used for treating or preventing vision loss and decline and eye diseases caused by optic nerve damage by protecting retinal nerve cells, and memory loss and learning due to brain nerve damage by protecting hippocampal nerve cells. It can be used for the treatment or prevention of deterioration, development and deterioration of depressive disorders and neurodegenerative diseases, and also for eye health such as improvement of memory and learning ability, stress relief, and protection of optic nerve and decreased vision. It can be used as a bar, pharmaceutical or food composition.
  • FIG. 1 is a diagram showing the free radical scavenging activity of DPPH ( ⁇ , ⁇ -diphenyl- ⁇ -picrylhydrazyl) of the Cassia tora extract (ST) and Cassia tora sprout extract (STS).
  • DPPH ⁇ , ⁇ -diphenyl- ⁇ -picrylhydrazyl
  • FIG. 2 is a diagram showing ABTS online antioxidant HPLC chromatograms of Cassia tora extract (ST) and Cassia tora sprout extract (STS).
  • the chromatogram of the blue line indicated in the upward direction is a diagram showing the components detected at 254 nm of ultraviolet (UV), and the chromatogram of the red line indicated in the downward direction reacts with the ABTS reagent to UV / VIS (ultraviolet / visible light) 734 nm
  • UV / VIS ultraviolet ultraviolet / visible light
  • FIG. 3 is a diagram showing ABTS online antioxidant HPLC chromatograms of bearer bud extracts (STS-C, STS-385, STS-465, STS-645 and STS-780) grown under various light conditions.
  • the chromatogram indicated in the upward direction is a diagram showing the components detected at ultraviolet (UV) 254 nm
  • the chromatogram indicated in the downward direction reacts with ABTS reagent to react with UV / VIS ( UV / Visible light)
  • UV / VIS UV / Visible light
  • the sample of (A) is a seedling sprout extract grown for 2 weeks under light-shielding conditions (STS of Example 1)
  • the sample of (B) is a seedling sprout extract grown for 2 weeks under normal light conditions (STS of Example 2)
  • the samples of C) and (C) were cultivated for 2 weeks under 385 nm LED illumination (STS-385 of Example 2), and the samples of (D) were cultivated for 2 weeks under 465 nm LED illumination
  • the extract (STS-465 of Example 2), the sample of (E) was cultivated for 2 weeks under 645 nm LED illumination, and the bud extract (STS-645 of Example 2), the sample of (F) was 780 nm LED illumination It was a cultivated shoot extract (STS-780 of Example 2) grown for 2 weeks under.
  • Figure 4 is an HPLC chromatogram showing the peaks of the main components separated from the bud extract (STS) of Example 1, which is an embodiment of the present invention.
  • Figure 5 is a comparative example 1 of the present invention extract (ST), cultivated bud extracts grown in light-shielding conditions (STS of Example 1) and cultivated bud extracts grown under various light conditions (STS, STS of Example 2) -C, STS-385, STS-465, STS-645 and STS-780) are graphs showing the efficacy of protecting damage to retinal progenitor cells (R28) caused by glutamate toxicity.
  • Figure 6 is a retinal progenitor cell induced by glutamate toxicity by concentration of each compound (Compounds 1 to 5 of Examples 4 and 5, and Compounds A to Compound X of Comparative Example 2) isolated from the seedling sprout extract (STS) (R28) It is a graph showing the efficacy of protecting damage.
  • Figure 7 is a comparative example 1 of the present invention extracts (ST), the seedling sprout extract grown under light-shielding conditions (STS of Example 1) and the seedling sprout extracts grown under various light conditions (STS, STS of Example 2) -C, STS-385, STS-465, STS-645 and STS-780) are graphs showing the efficacy of protecting hippocampal nerve cell (HT-22) damage caused by glutamate toxicity.
  • STS of Example 1 the seedling sprout extract grown under light-shielding conditions
  • STS, STS of Example 2 the seedling sprout extracts grown under various light conditions
  • STS-385, STS-465, STS-645 and STS-780 are graphs showing the efficacy of protecting hippocampal nerve cell (HT-22) damage caused by glutamate toxicity.
  • the present invention may relate to a naphthopyrone derivative of Formula 1, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof.
  • the naphthopyrone derivative of Formula 1 may be 7-hydroxymusizinyl-rubrofusarin-8'-O-glucoside (7-hydroxymusizinyl-rubrofusarin-8'-O-glucopyranoside).
  • pharmaceutically acceptable means the approval of a government or equivalent regulatory body to use in animals, more specifically in humans, by avoiding significant toxic effects when used in conventional medical dosages. It is meant to be recognized or approved, or recognized as listed in a pharmacopeia or other general pharmacopeia.
  • salts means salts according to one aspect of the invention that are pharmaceutically acceptable and have the desired pharmacological activity of the parent compound.
  • the salt is formed from (1) an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or the like; Or acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3- (4-hydroxybenzoyl) Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenes
  • optical isomers eg, essentially pure enantiomers, essentially pure diastereomers or mixtures thereof
  • conformational isomers conformation isomers (i.e., isomers differing only in that angle of one or more chemical bonds), positional isomers (especially tautomers) or geometric isomers (e.g., cis-trans isomers) do.
  • “essentially pure”, when used in connection with, for example, enantiomers or diastereomers, contains at least about 90%, preferably at least about 95% of specific compounds that may exemplify enantiomers or diastereomers. , More preferably at least about 97% or at least about 98%, even more preferably at least about 99%, even more preferably at least about 99.5% (w / w).
  • hydrate refers to a compound to which water is bound, and is a broad concept including an inclusion compound having no chemical bonding force between water and the compound.
  • solvate refers to a higher order compound formed between molecules or ions of a solute and molecules or ions of a solvent.
  • the present invention provides one or more naphthopyrone derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvents thereof selected from the group consisting of naphthopyrone derivatives of the following Chemical Formulas 1 to 5
  • a method for preparing a cargo comprising the naphthopyron derivative, its stereoisomer, pharmaceutically acceptable salt thereof, hydrate thereof, or solvate thereof from Sprout of Cassia obtusifolia L. or Cassia tora L.
  • a method for preparing a naphthopyron derivative, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate thereof comprising the step of separating one or more selected from the group.
  • the compound of formula 1 may be 7-hydroxymushizinyl-rubbrofusarin-8'-O-glucoside
  • the compound of formula 2 is isotolactone ( isotoralactone)
  • the compound of formula 3 may be toralactone (toralactone)
  • the compound of formula 4 may be torosacrysone (torosachrysone)
  • the The compound of Formula 5 may be rubrofusarin.
  • the sprout may be grown by short-term germination of seeds, germinated seeds indoors, or may be a sprout that is generally sold.
  • the sprouted or sprouted plant of the above-described manufacturing method was seeded from the seeded plant ( Cassia obtusifolia L.) or Ginseng tea ( Cassia tora L. or Senna tora ), and then grown or grown naturally for 2 to 31 days.
  • It may be a sprout or a young plant, specifically 2 days or more, 3 days or more, 4 days or more, 5 days or more, 6 days or more, 7 days or more, 8 days or more, 9 days or more, 10 days or more, 11 days or more, 12 days or more, 13 days or more, 14 days or more, 15 days or more, 16 days or more, 17 days or more, 18 days or more, 19 days or more, 20 days or more, 21 days or more, 22 days or more, 23 days or more, 24 days More than 25 days, more than 26 days, more than 27 days, more than 28 days, more than 29 days or more than 30 days Naturally grown or grown buds or young plants, 31 days or less, 30 days or less, 29 days or less, 28 days or less, 27 days or less, 26 days or less, 25 days or less, 24 days or less, 23 days or less, 22 days or less, 21 days or less, 20 days or less, 19 days or less, 18 days or less, 1 7 days or less, 16 days or less, 15 days or less, 14 days or less,
  • the term ( Cassia obtusifolia L. or Cassia tora L.) refers to the herbaceous genus of dicotyledonous plant family Rosaceae, and the term of the term (Cassia obtusifolia L.) or Ginseng tea (Cassia tora L. or Senna) tora) as mature seeds, the extract of terminator is known to improve diabetes, improve dyslipidemia, protect liver, antibacterial, and lower blood pressure (Dong, X. et al. Mol. Med. Rep. 2017, 16, 2331-2346) , It is not known about the efficacy of improving or inhibiting the damage of retinal nerve cells or hippocampal nerve cells due to oxidative stress or drug toxicity, especially glutamate.
  • the germinating bud or young plant may be all or part of the germinating bud or young plant.
  • the part may be an outpost or above ground or underground.
  • the ground portion may be a stem, a leaf, a flower, or a combination thereof.
  • the basement part may be a root.
  • the plant may be naturally grown or artificially cultivated.
  • the bud of the present invention can be easily grown indoors and can be grown and used for a short period of time within several weeks without supplying additional nutrients, so it has the advantage of great industrial utility.
  • the shoot sprout extract also includes a crude extract (crude extract) or an additional fraction (fractionation) of the extract.
  • the seedling sprout extract may be a crude extract, fraction, or a combination thereof.
  • the crude extract refers to the one obtained by contacting the sprouted bud with the extraction solvent.
  • the fraction refers to the separation of a substance containing specific components with respect to the crude extract.
  • the extract, or a fraction thereof may be an extract of a shoot sprout plant, a fraction thereof, or a small fraction of each of the compositions of the present invention, or as a mixture thereof.
  • the small fraction may be obtained by passing an ultrafiltration membrane having a cut-off value, and may be obtained by column chromatography or solvent fractionation.
  • the sprout bud extract or fraction may contain one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of the formula (1) to (5).
  • the separation may be by filtration, dipping, centrifugation, solvent fractionation, chromatography or a combination thereof.
  • the chromatography is prepared for separation according to various conditions, i.e., size, charge, hydrophobicity or affinity, ion exchange chromatography, affinity chromatography, size exclusion chromatography, HPLC, high-speed chromatography, column chromatography, reverse phase Column chromatography or combinations thereof.
  • the extraction may include incubating the plant in a solvent for a period of time.
  • the extraction may be performed with or without stirring, or may include heating.
  • the incubation may be performed at room temperature to reflux temperature with or without stirring.
  • Incubation temperature may be appropriately selected depending on the solvent selected. For example, the temperature may be from room temperature to reflux temperature, from 30 ° C. to reflux temperature, and from 40 ° C. to reflux temperature.
  • the heating may include heating to 50 ° C., 60 ° C., 70 ° C., 80 ° C., or reflux temperature.
  • the heating may be to 50 °C to reflux temperature, 60 °C to reflux temperature, 70 °C to reflux temperature, 80 °C to reflux temperature, or to the reflux temperature.
  • the extraction time may vary depending on the temperature selected, for example 1 hour to 2 months, for example 1 hour to 1 month, 1 hour to 15 days, 1 hour to 10 days, 1 hour to 5 days, 1 hour to 3 days. , 1 hour to 2 days, 1 hour to 1 day, 5 hours to 1 month, 5 hours to 15 days, 5 hours to 10 days, 5 hours to 5 days, 5 hours to 3 days, 5 hours to 2 days, 5 Hour to 1 day, 10 hours to 1 month, 10 hours to 15 days, 10 hours to 10 days, 10 hours to 5 days, 10 hours to 3 days, or 10 hours to 2 days.
  • the extraction may be to extract the plant under reflux in a solvent.
  • the solvent may have a volume of 1 times, 2 times, 5 times, 10 times, or 15 times or more with respect to the weight of the plant.
  • the solvent may have a volume of 1 to 15 times, 2 to 15 times, 5 to 15 times, 10 times to 15 times, or about 15 times the weight of the plant.
  • the plant may be dried in shade or shading facility or warm air or drying device.
  • the extraction method conventional methods in the art such as filtration, hot water extraction, dipping extraction, cold dipping, microwave extraction, reflux cooling extraction, pressure extraction, subcritical extraction, supercritical extraction, and ultrasonic extraction may be used.
  • Immersion extraction may be to be immersed at warm or room temperature, it may be one to five times to extract.
  • the seedling sprout plant may be in contact with the extraction solvent of 0.1 to 10 times or 1 to 6 times.
  • Cold needle extraction temperature may be 20 °C to 40 °C.
  • the warm needle or heat extraction temperature may be 40 ° C to 100 ° C.
  • Cold needle extraction time may be 24 hours to 120 hours, the temperature of the hot or heated extraction may be 0.5 hours to 48 hours.
  • the extraction may also include removing the solvent from the extract obtained by known methods such as evaporation or reduced pressure concentration.
  • the extraction may also include preparing a dry extract by drying the obtained extract, such as lyophilization.
  • the decompression concentration may be to use a vacuum decompression concentrator or a vacuum rotary evaporator.
  • the drying may be drying under reduced pressure, vacuum drying, boiling drying, spray drying or freeze drying.
  • the manufacturing method may further include the step of extracting the missing sprout as a solvent selected from the group consisting of water, C1 to C6 alcohol, and a mixed solvent thereof.
  • the alcohol may be C1 to C3 alcohol, C1 to C4, C1 to C5, or C1 to C6 alcohol.
  • the alcohol may be a primary alcohol.
  • the alcohol of C1 to C6 may be methanol, ethanol, propanol, isopropanol, butanol or a mixture thereof.
  • the preparation method may further comprise the step of fractionating to at least one selected from the group consisting of water, ethyl acetate, hexane, methylene chloride, chloroform, methanol, ethanol, acetone, and a mixed solvent thereof.
  • the preparation method is based on the total weight of the extract obtained through the extraction of the shoots sprouts one or more naphthopyron derivatives selected from the group consisting of the naphthopyrone derivatives of Formula 1 to Formula 5, stereoisomers thereof, Pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, which may comprise the step of preparing a shoot sprout fraction comprising 1 to 20% by weight, specifically 1% by weight, 2% by weight, At least 3 wt%, at least 4 wt%, at least 5 wt%, at least 6 wt%, at least 7 wt%, at least 8 wt%, at least 9 wt%, at least 10 wt%, at least 11 wt%, at least 12 wt%, It may be to include a process for producing a fraction of the shoots containing at least 13% by weight, at least 14% by weight, at least 15% by weight, at least 16% by weight, at least 17% by weight, at least 18% by weight or at least
  • One or more naphthopyron derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof selected from the group consisting of naphthopyrone derivatives of Formulas 1 to 5 may be May be included in the range of 1 to 50% by weight, specifically, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight, 6% by weight, 7% by weight % By weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight, 16% by weight, 17% by weight At least 18% by weight at least 19% by weight at least 20% by weight at least 21% by weight at least 22% by weight at least 23% by weight at least 24% by weight at least 25% by weight at least 26% by weight.
  • % By weight, 28% by weight, 29% by weight, 30% by weight, 31% by weight, 32% by weight At least 33 wt%, at least 34 wt%, at least 35 wt%, at least 36 wt%, at least 37 wt%, at least 38 wt%, at least 39 wt%, at least 40 wt%, at least 41 wt%, 42 wt% At least 43 wt%, at least 44 wt%, at least 45 wt%, at least 46 wt%, at least 47 wt%, at least 48 wt% or at least 49 wt%, and at most 50 wt%, at most 49 wt%, 48 wt% or less, 47 wt% or less, 46 wt% or less, 45 wt% or less, 44 wt% or less, 43 wt% or less, 42 wt% or less, 41 wt% or less, 40 wt% or less, 39 wt
  • the present invention provides at least one naphthopyrone derivative, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvent thereof.
  • the one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 are from the naphthopyrone derivatives of Formula 1 and the naphthopyrone derivatives of Formulas 2 to 5 It may be one or more selected naphthopyrone derivatives.
  • Descriptions of the naphthopyrone derivatives of Formulas 1 to 5, pharmaceutically acceptable salts, stereoisomers, hydrates, solvates, modified buds, modified bud extracts or fractions are as described above.
  • the composition may be a composition for protecting neurons or inhibiting neuronal death, and specifically, may be a composition for protecting neurons or inhibiting neuronal death from oxidative stress induced by metabolic toxicity, neurotoxicity, chemical causes, and the like.
  • the oxidative stress may be caused by glutamate, glutamate toxicity, or glutamate neurotoxicity, or calcium homeostatic dysregulation, mitochondrial dysfunction, excitatory cytotoxicity, similar to oxidative stress caused by glutamate neurotoxicity, Oxidative stress, such as depletion of nutritional factors.
  • the composition may reduce, inhibit, ameliorate, or prevent damage to retinal neurons or hippocampal neurons caused by glutamate, glutamate toxicity, or glutamate neurotoxicity, or resuscitate or kill dead retinal neurons or hippocampal neurons. It may be regenerative and protects nerve cells by regulating antioxidant activation or glutamate metabolism, which is a defense against oxidative stress caused by glutamate neurotoxicity, abnormalities in calcium homeostasis, mitochondrial dysfunction, excitatory cytotoxicity, depletion of nutritional factors, etc. Or inhibit neuronal cell death.
  • the extract of shoot sprouts has a DPPH free radical scavenging effect of 1.7 times or more superior to the extract of shoot shoots (Test Example 1), and the compounds of Formula 1 to Formula 5 corresponding to antioxidant components (naph Topirone derivative) has a high content and shows a better antioxidant effect (Test Example 2)
  • the composition of the present invention is an antioxidant action that is a defense mechanism against oxidative stress is activated to protect neurons or inhibit neuronal cell death Was confirmed to be excellent.
  • the composition may be treated before, concurrent with, or after development of neuronal damage or death.
  • the composition is a group consisting of at least one naphthopyrone derivative selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof.
  • sprout extract or a sprout sprout fraction comprising the same may comprise 0.001% to 80% by weight relative to the total weight of the composition, specifically 0.001% or more, 0.01% or more, 0.05% or more, 0.1% or more, 1% or more, 2% or more, 3% or more, 4% or more, 5% or more, 10% or more, 20 wt% or more, 30 wt% or more, 40 wt% or more, or 60 wt% or more, 80 wt% or less, 60 wt% or less, 40 wt% or less, 30 wt% or less, 20 wt% or less, 10 It may include less than 5% by weight, less than 5% by weight, less than 4% by weight, less than 3% by weight, less than 2% by weight, or less than 1% by weight.
  • the above-mentioned sprout extract or fraction is one or more naphthopyron derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or the like selected from the group consisting of naphthopyrone derivatives of the above Chemical Formulas 1 to 5.
  • Solvate may comprise from 1 to 50% by weight, based on the total weight of the shoot sprout extract or fraction, specifically, 1% by weight, 2% by weight, 3% by weight, 4% by weight, 5% by weight % By weight, 6% by weight, 7% by weight, 8% by weight, 9% by weight, 10% by weight, 11% by weight, 12% by weight, 13% by weight, 14% by weight, 15% by weight At least 16% by weight at least 17% by weight at least 18% by weight at least 19% by weight at least 20% by weight at least 21% by weight at least 22% by weight at least 23% by weight at least 24% by weight.
  • % By weight, 26% by weight, 27% by weight, 28% by weight, 29% by weight At least 30%, at least 31% by weight, at least 32% by weight, at least 33% by weight, at least 34% by weight, at least 35% by weight, at least 36% by weight, at least 37% by weight, at least 38% by weight, at 39% by weight At least 40% at least 41% at least 42% at least 43% at least 44% at least 44% at least 45% at least 46% at least 47% at least 48% or at least 49% It may include at least 50%, up to 49%, up to 48%, up to 47%, up to 47%, up to 46%, up to 45%, up to 44%, up to 43%, up to 42% Up to 41 wt%, up to 40 wt%, up to 39 wt%, up to 38 wt%, up to 37 wt%, up to 36 wt%, up to 35 wt%, up to 34 wt%, up to 33 wt
  • the nerve cell may be a central nerve, a peripheral nerve or an optic nerve associated with the brain hippocampus or the eye retina, and specifically, may be a retinal nerve cell or a hippocampal nerve cell.
  • the retinal nerve cells are rod cells, cone cells, bipolar cells, retinal amacrine cells, horizontal cells and retinal ganglion cells. It may be one or more cells selected from the group consisting of).
  • the rod cells and cone cells are nerve cells that sense light by sensing light, and the dipole cells, retinal amacrine cells, and horizontal cells are nerve cells that transmit visual information to the retinal ganglion cells, and the retinal ganglion cells are retinal ganglion cells. It is a nerve cell that delivers visual information to the brain.
  • R28 retinal progenitor cells or R28 retinal progenitor cells of the present invention express the traits of various constituent cells of the retina and survive even when transplanted into the retina, apoptosis occurs due to hypoxia or serum deficiency, It can also be useful for apoptosis and cytotoxicity studies that are linked to related glutamate or GABA receptor expression.
  • R28 cells can differentiate from retinal progenitor cells to retinal ganglion cells depending on the culture conditions, and can be used not only for overall cytological studies of the retina, but also for basic research of retinal ganglion cells (Jungil Lee, Jaewoo Kim, Korean Ophthalmology) Journal, 2009, 50, 919-922).
  • the hippocampal nerve cells are nerve cells of the hippocampus (hippocampus), which is a structure of the medial temporal lobe of the brain, and the hippocampus is vulnerable to physiological / oxidative stress stimulation and is known as a central tissue causing damage to cognitive function due to stress. May cause hippocampal structure, brain cell production, synaptic plasticity, and behavioral changes associated with hippocampus (Kim, Eun-ju, Korean Psychological Association: Cognitive and Biological, 2012, 24, 65-88).
  • HT-22 hippocampal neurons of one embodiment of the present invention can be used as an in vitro model system for studying neurotoxicity induced by oxidative stress due to sensitivity to glutamate (Liu, J. et al. Life Science , 2009, 84, 267-271; Kim Ji-hyun, Jeon Soon-sil, Korean Journal of Food Science and Nutrition, 2017, 46, 886-890).
  • the present invention provides at least one naphthopyrone derivative, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvent thereof.
  • Injury of retinal nerve cells or hippocampal nerve cells comprising as an active ingredient at least one selected from the group consisting of cargo, Cassia obtusifolia L. or Cassia tora L. Or it may be directed to a composition for preventing or treating a neurologically damaging disease caused by death, or may be related to a composition for preventing or treating a neurologically damaging disease caused by glutamate neurotoxicity.
  • the at least one naphthopyrone derivative selected from the group consisting of naphthopyrone derivatives of Formulas 1 to 5 is selected from the group consisting of naphthopyrone derivatives of Formula 1 and naphthopyrone derivatives of Formulas 2 to 5 It may be one or more naphthopyrone derivatives.
  • the neurological damaging disease caused by damage or death of the retinal nerve cells or hippocampal nerve cells may be due to glutamate neurotoxicity, and the description of the retinal nerve cells and hippocampal nerve cells is as described above.
  • the neurological damaging disease may be at least one selected from the group consisting of diabetic retinopathy due to retinal nerve cell injury or death, macular degeneration, vision disorder due to retinal cell damage, retinal pigmentation, retinal detachment, retinal vessel occlusion and glaucoma.
  • the disease May be one or more selected from the group consisting of memory loss, loss of learning ability, depressive disorder, amyotrophic lateral sclerosis (Lou Gehrig's disease), Parkinson's disease and cerebral ischemic nerve injury due to hippocampal nerve cell injury or death,
  • the disease is not limited as long as the disease is caused by damage or death of retinal nerve cells or hippocampal nerve cells.
  • the glutamate neurotoxicity refers to toxicity caused by glutamate acting as an oxidative neurotoxic substance due to a rapid increase in glutamate concentration outside the neuron.
  • the glutamate neurotoxicity may be caused by glutamate introduced from outside of the subject, and the influx of glutamate may be ingested with food containing glutamate, therapeutic agent containing glutamate, preventive agent containing glutamate, antibiotic containing glutamate, and the like. Or by administration, but is not limited thereto.
  • One or more naphthopyron derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 may be separated or purified from the sprout ( Cassia obtusifolia L. or Cassia tora L.), specifically, the sprout
  • the ethanol extract may be separated or purified from the ethanol extract, and the ethanol extract from the shoots may be fractionated with ethyl acetate, and then the ethyl acetate fraction may be separated by chromatography, or the ethyl acetate fraction may be separated with a mixed solvent of hexane, methylene chloride and methanol. It may be fractionated and separated by chromatography.
  • the seedling sprout extract may be extracted as a solvent selected from the group consisting of water, C1 to C6 alcohol and a mixed solvent thereof.
  • the alcohol may be C1 to C3 alcohol, C1 to C4, C1 to C5, or C1 to C6 alcohol.
  • the alcohol may be a primary alcohol.
  • the alcohol of C1 to C6 may be methanol, ethanol, propanol, isopropanol, butanol or a mixture thereof.
  • the fraction may further include fractionating into one or more selected from the group consisting of water, ethyl acetate, hexane, methylene chloride, chloroform, methanol, ethanol, acetone, and a mixed solvent thereof.
  • the one or more naphthopyrone derivatives selected from the group consisting of naphthopyrone derivatives of the formula (1) to (5) is contained in a higher content in the shoot sprout extract than the extract of the fault as an antioxidant component (Test Example 2), the naphthopyron derivative is excellent in protecting the retinal nerve cells (R28) and hippocampal nerve cells (HT-22) damaged or killed by glutamate treatment (Test Examples 4 and 6).
  • the naphthopyrone derivatives of Formulas 1 to 5 are effective ingredients of the shoot sprout having the efficacy of preventing or treating neuronal damage diseases caused by glutamate neurotoxicity.
  • the present invention provides at least one naphthopyrone derivative, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvent thereof. At least one selected from the group consisting of cargoes, Cassia obtusifolia L. or Cassia tora L. Sprout extracts comprising the same, or may be related to the composition for antioxidant, comprising a fraction of the sprouts containing the same as an active ingredient.
  • the at least one naphthopyrone derivative selected from the group consisting of naphthopyrone derivatives of Formulas 1 to 5 is selected from the group consisting of naphthopyrone derivatives of Formula 1 and naphthopyrone derivatives of Formulas 2 to 5 It may be one or more naphthopyrone derivatives.
  • the present invention in one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formula 1 to Formula 5 in the individual in need of neuronal cell protection from oxidative stress or neuronal cell death inhibition, the stereoscopic thereof One or more selected from the group consisting of isomers, pharmaceutically acceptable salts thereof, hydrates, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extracts, or missing bud fractions comprising the same It may be related to a method for protecting neurons from oxidative stress or inhibiting neuronal death. In one aspect of the present invention, administration of the method may be performed according to the administration method and administration dose described herein.
  • the present invention is selected from the group consisting of the naphthopyrone derivatives of Formula 1 to Formula 5 in the individual in need of prevention or treatment of neuro-injury disease caused by damage or death of retinal nerve cells or hippocampal nerve cells.
  • It may be related to a method for preventing or treating a neuro-damaging disease caused by damage or death of retinal nerve cells or hippocampal nerve cells, comprising administering a bud extract or a bud fraction containing a bud thereof.
  • administration of the method may be performed according to the administration method and administration dose described herein.
  • the present invention is a naphthopyrone derivative selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 in an individual in need of antioxidant, stereoisomers thereof, pharmaceutically acceptable salts thereof, and hydrates thereof , Or one or more selected from the group consisting of solvates thereof, and related to an antioxidant method comprising administering a bud extract comprising Cassia obtusifolia L. or Cassia tora L., or a bud bud fraction comprising the same. have.
  • administration of the method may be performed according to the administration method and administration dose described herein.
  • the present invention is one or more naphthopyrones selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for preparing a pharmaceutical composition for protecting neurons from oxidative stress or inhibiting neuronal death.
  • One or more selected from the group consisting of derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extracts, or combinations thereof This may be related to the use of the fraction of the sprouted shoots.
  • the present invention is a naphthopyrone derivative of Chemical Formulas 1 to 5 for preparing a pharmaceutical composition for the prevention or treatment of neuro-injury disease caused by damage or death of retinal nerve cells or hippocampal nerve cells.
  • the present invention is one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for preparing a pharmaceutical composition for antioxidant, stereoisomers thereof, and pharmaceutically acceptable thereof It may be related to the use of at least one selected from the group consisting of salts, hydrates thereof, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extracts, or the named bud fractions comprising the same.
  • the present invention is one or more naphthopyrones selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for preparing a cosmetic composition for protecting neurons from oxidative stress or inhibiting neuronal death.
  • One or more selected from the group consisting of derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extracts, or combinations thereof This may be related to the use of the fraction of the sprouted shoots.
  • the present invention is a naphthopyrone of Formula 1 to Formula 5 for preparing a cosmetic composition for improving, preventing or treating a neuro-damage disease caused by damage or death of retinal nerve cells or hippocampal nerve cells.
  • One or more naphthopyrone derivatives selected from the group consisting of derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, one or more selected from the group consisting of, Cassia obtusifolia L. Or Cassia tora L.) bud extract, or the use of a named bud fraction comprising the same.
  • the present invention is one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for preparing a cosmetic composition for antioxidant, stereoisomers thereof, and pharmaceutically acceptable thereof It may be related to the use of at least one selected from the group consisting of salts, hydrates thereof, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extracts, or the named bud fractions comprising the same.
  • the present invention is one or more naphthopyrones selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for preparing a food composition for protecting neurons from oxidative stress or inhibiting neuronal death.
  • One or more selected from the group consisting of derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extracts, or combinations thereof This may be related to the use of the fraction of the sprouted shoots.
  • the present invention is a naphthopyrone of Formula 1 to Formula 5 for preparing a food composition for improving, preventing or treating a neuro-damaging disease caused by damage or death of retinal nerve cells or hippocampal nerve cells.
  • One or more naphthopyrone derivatives selected from the group consisting of derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, one or more selected from the group consisting of, Cassia obtusifolia L. Or Cassia tora L.) bud extract, or the use of a named bud fraction comprising the same.
  • the present invention is one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for preparing a food composition for antioxidant, stereoisomers thereof, and pharmaceutically acceptable thereof It may be related to the use of at least one selected from the group consisting of salts, hydrates thereof, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extracts, or the named bud fractions comprising the same.
  • the present invention is one or more naphthopyrones selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for preparing a quasi-drug composition for protecting neurons from oxidative stress or inhibiting neuronal death.
  • One or more selected from the group consisting of derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extracts, or combinations thereof This may be related to the use of the fraction of the sprouted shoots.
  • the present invention is a naphthopyrone of Formula 1 to Formula 5 for preparing a quasi-drug composition for the improvement, prevention or treatment of a neuro-damage disease caused by damage or death of retinal nerve cells or hippocampal nerve cells.
  • One or more naphthopyrone derivatives selected from the group consisting of derivatives, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, or solvates thereof, one or more selected from the group consisting of, Cassia obtusifolia L. Or Cassia tora L.) bud extract, or the use of a named bud fraction comprising the same.
  • the present invention is one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for preparing a quasi-drug composition for antioxidant, stereoisomers thereof, and pharmaceutically acceptable thereof It may be related to the use of at least one selected from the group consisting of salts, hydrates thereof, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extracts, or bear sprout fractions comprising them.
  • one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5, stereoisomers thereof, pharmaceutically acceptable salts, hydrates thereof, or solvents thereof
  • one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5, stereoisomers thereof, pharmaceutically acceptable salts, hydrates thereof, or solvents thereof
  • one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5, stereoisomers thereof, pharmaceutically acceptable salts, hydrates thereof, or solvents thereof
  • the present invention is one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for protecting neurons from oxidative stress or inhibiting the death of neurons. At least one selected from the group consisting of stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates, or solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extract, or crystals comprising the same It may be related to the use of the sprout fraction.
  • the present invention is selected from the group consisting of naphthopyrone derivatives of Formula 1 to Formula 5 for preventing or treating neuro-injury diseases caused by damage or death of retinal nerve cells or hippocampal nerve cells.
  • the present invention is one or more naphthopyrone derivatives selected from the group consisting of the naphthopyrone derivatives of Formulas 1 to 5 for antioxidant, stereoisomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof, Or it may be related to the use of at least one selected from the group consisting of solvates thereof, Cassia obtusifolia L. or Cassia tora L. bud extract, or a named bud fraction comprising the same.
  • composition of the present invention may be a pharmaceutical composition, cosmetic composition or food composition.
  • compositions according to one aspect of the invention may be formulated in oral or parenteral dosage forms.
  • it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants.
  • Solid form preparations for oral administration include tablets, pills, powders, granules, soft or hard capsules, and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, or the like. Or lactose, gelatin, or the like is mixed.
  • lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral administration include suspending agents, intravenous solutions, emulsions, syrups, etc.
  • various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories.
  • a non-aqueous solvent and a suspension solvent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used.
  • As a base for suppositories witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used.
  • compositions according to one aspect of the invention may be used in the form of their pharmaceutically acceptable salts, and may also be used alone or in combination with other pharmaceutically active compounds as well as in a suitable collection.
  • the salt is not particularly limited as long as it is pharmaceutically acceptable.
  • hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, methanesulfonic acid , Benzene sulfonic acid, toluene sulfonic acid, naphthalene sulfonic acid and the like can be used.
  • Parenteral dosage forms may also be dermal application patches, ointments, creams, eye drops, sprays or injections.
  • the invention may be a method for protecting neurons in a subject comprising administering the pharmaceutical composition to the subject.
  • the subject may be a mammal, eg, a human, a cow, a horse, a pig, a dog, a sheep, a goat, or a cat, the mammal may be a human, and an effective dosage for a human body of a compound of the invention Depends on the age, weight, sex, dosage form, health condition and degree of disease of the patient.
  • a mammal eg, a human, a cow, a horse, a pig, a dog, a sheep, a goat, or a cat
  • an effective dosage for a human body of a compound of the invention Depends on the age, weight, sex, dosage form, health condition and degree of disease of the patient.
  • the administration may be administered in various formulations for oral administration or parenteral administration such as intravenous, intraperitoneal, intradermal, subcutaneous, epithelial or intramuscular administration, and when formulated, commonly used fillers, extenders, binders, wetting agents, shelf life It is prepared using diluents or excipients such as releases, surfactants and the like.
  • the administration can be administered by methods known in the art. Administration can be administered directly to the subject by any means, eg, by intravenous, intramuscular, oral, or subcutaneous administration.
  • the administration can be administered systemically or locally.
  • the administration may be locally administered to a site where neurons are present or expected to occur.
  • Food composition according to an aspect of the present invention may be a health functional food composition.
  • the food composition is not particularly limited in dosage form, but may be formulated in a form in which the concentrate or powder is ingested or ingested directly or diluted, for example, a liquid such as tablets, granules, powders, drinks, caramels , Gels, bars and the like.
  • the food composition of each formulation may be suitably selected by those skilled in the art according to the formulation or purpose of use in addition to the active ingredient, and a synergistic effect may occur when simultaneously applied with other raw materials.
  • the food composition may contain various flavors or natural carbohydrates as additional ingredients.
  • the natural carbohydrate may be glucose, monosaccharides such as fructose, maltose, disaccharides such as sucrose, and polysaccharides such as dextrin, cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol.
  • sweetener natural sweeteners such as taumatin and stevia extract, and synthetic sweeteners such as saccharin and aspartame can be used.
  • the ratio of the natural carbohydrate may be selected from 0.01 to 0.04 parts by weight, specifically about 0.02 to 0.03 parts by weight per 100 parts by weight of the composition.
  • the food composition may contain various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonic acid. Carbonating agents and the like used in beverages.
  • the functional food of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These ingredients can be used independently or in combination. The proportion of such additives is not so critical but is typically included in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition herein.
  • the dosage determination of the active ingredient is within the level of those skilled in the art, the daily dosage of which is for example from 0.1 mg / kg / day to 5000 mg / kg / day, more specifically 50 mg / kg It may be / day to 500 mg / kg / day, but is not limited thereto, and may vary depending on various factors such as age, health condition, complications of the subject to be administered.
  • the food composition according to one aspect of the present invention includes, for example, health products including chewing gum, caramel products, candy, ice cream, confectionary, various food products such as soft drinks, mineral water, alcoholic beverages, vitamins and minerals, and the like. Functional foods.
  • composition of the present invention may be a quasi-drug composition.
  • the term 'out of quasi-drugs' refers to drugs based on the classification criteria set by the Ministry of Health and Welfare for articles that have less effect on the human body than drugs used for the treatment or prevention of diseases according to the Pharmaceutical Affairs Act. do. Therefore, it may include fiber and rubber products used for the treatment or prevention of human or animal diseases, mild or non- direct action on the human body, non-apparatus or machinery, and the like, or disinfectants and insecticides to prevent infectious diseases. Can be.
  • the quasi-drug composition of the present invention may be for the improvement, protection or treatment of damage to nerve cells by oxidative stress, may be for the prevention or improvement of neurological damage diseases caused by glutamate neurotoxicity.
  • the quasi-drug composition may further include an quasi-pharmaceutically acceptable excipient or carrier.
  • the quasi-drug composition may be formulated in the form of skin smear, cream, paste, eye drop, spray.
  • the dried plant was placed in an extraction container, 5.5 L of ethanol was added thereto, shaken at room temperature, stirred and extracted for 7 days, and the mixture was mixed with a Whatman paper filter paper having a film thickness of 0.34 mm and a diameter of 30.
  • the process of gravity filtration using a cm glass funnel was repeated twice ('extraction-filtration' twice) to obtain a filtered extract.
  • the filtered extract was placed in a reduced pressure concentrator and concentrated by evaporation of the solvent completely at 35 ° C. under reduced pressure to obtain 66.7 g (hereinafter, referred to as 'STS') of Clarified Sprout Extract (yield 9.55%).
  • the seedling sprouts were grown by varying the light wavelength conditions. Cultivated buds are grown in the same manner as in Example 1, but the selective light quality of the fluorescent light, LED 385 nm, 465 nm, 645 nm, 780 nm, respectively, in a large amount of wavelength, not light-shielding conditions at the time of growing the germination buds Irradiated with light, each was grown for 6 days.
  • each of the extracts of Cultivated Sprout was prepared in the same manner as in Example 1, and the extracts obtained by cultivating under fluorescent light conditions were 'STS-C' under LED light conditions of 385 nm.
  • 'STS-385' the extract obtained by cultivation under the light condition of LED 465 nm, 'STS-465', the extract obtained by cultivating under the light condition of LED 645 nm 'STS-645', LED 780 nm
  • the extract obtained by cultivation under light condition of 'STS-780' was called.
  • ethyl acetate fraction (STS- EA) 23.5 g were obtained.
  • the ethyl acetate fraction was mixed with methylene chloride (or ethyl acetate) alone or with a mixed solvent of n -hexane, methylene chloride (or ethyl acetate) and methanol (or ethanol) ( n -hexane: methylene chloride mixture ratio (volume ratio) of 1).
  • the ethyl acetate fraction (STS-EA) is contacted with the eight fraction solvents, stirred in celite to evaporate the solvent, and silica packed in a column having a diameter of 10 cm and a length of 20 cm. ) was developed in the resin. Chromatography eluting with each of the above solvents yielded 20 fractions (STS-EA-fraction 1 to STS-EA-fraction 20).
  • STS-EA-fraction 12 prepared in Example 3 (the second fraction of the three fractions in which the elution solvent in Example 3 is methylene chloride (or ethyl acetate): methanol (or ethanol) mixing ratio 10: 1)
  • preparative column chromatography was performed under the following separation method 1 to separate Compound 1 having the structure of Formula 1 at a retention time of about 221 minutes. (14.0 mg, 0.002% by weight of dry plant; 0.021% by weight of dry extract)
  • STS-EA-fraction 12 prepared in Example 3 (the second fraction of the three fractions in which the elution solvent in Example 3 is methylene chloride (or ethyl acetate): methanol (or ethanol) mixing ratio 10: 1)
  • preparative column chromatography was performed under the condition of separation method 1 of Example 4 to separate 1.2 mg of Compound 3 having the structure of Chemical Formula 3 at a retention time of about 24 minutes.
  • the STS-EA-fraction 8 of Example 3 (the first fraction of the three fractions in which the elution solvent in Example 3 is methylene chloride (or ethyl acetate): methanol (or ethanol) mixing ratio 50: 1) is concentrated under reduced pressure. Then, under the conditions of the following separation method 2, preparative column chromatography was performed to separate 7.5 mg of compound 2 having the structure of formula 2 at a retention time of about 36 minutes.
  • Example 3 STS-EA-fraction 13 (third fraction out of three fractions in which the elution solvent in Example 3 is methylene chloride (or ethyl acetate): methanol (or ethanol) mixing ratio 10: 1) is concentrated under reduced pressure. Then, under the conditions of the following separation method 3, preparative column chromatography was performed to separate 0.6 mg of Compound 4 having the structure of Formula 4 between the retention time of about 71 minutes, and the Chemical Formula 5 at the retention time of about 120 minutes. 2.6 mg of Compound 5 having the structure of was isolated.
  • the STS-EA-fraction 8 of Example 3 was concentrated under reduced pressure, and preparative column chromatography was performed under the conditions of the separation method 2 of Example 4 to separate the components contained in the fraction. As a result, 7.2 mg of Compound C corresponding to Peak C of FIG. 4, 0.8 mg of Compound D corresponding to Peak D of FIG. 4, and 2.5 mg of Compound E corresponding to Peak E of FIG. 4 were isolated.
  • STS-EA-fraction 16 obtained in Example 3 (the third fraction of the three fractions in which the elution solvent in Example 3 is methylene chloride (or ethyl acetate): methanol (or ethanol) mixing ratio 5: 1)
  • silica gel column chromatography was performed under the following separation method 5 to fractionate into 14 small fractions.
  • the peak of FIG. 4 2.5 mg of compound M corresponding to M, 2.1 mg of compound N corresponding to peak N in FIG. 4, and 0.5 mg of compound O corresponding to peak O in FIG. 4 were separated.
  • STS-fraction 17 obtained in Example 3 (the first fraction of the three fractions in which the elution solvent in Example 3 is methylene chloride (or ethyl acetate): methanol (or ethanol) mixing ratio 3: 1) is concentrated under reduced pressure. Subsequently, the components containing the fractions were separated by HPLC separation under the conditions of Separation Method 9 below. As a result, 1.7 mg of Compound Q corresponding to the peak Q of FIG. 4 was isolated.
  • the STS-EA-fraction 18 obtained in Example 3 (the second fraction of the three fractions in which the elution solvent in Example 3 is methylene chloride (or ethyl acetate): methanol (or ethanol) mixing ratio 3: 1) is reduced.
  • silica gel column chromatography was performed under the conditions of the following separation method 10 to fractionate into 24 small fractions.
  • the small fractions 17 to 21 (the third and fourth fractions of the four small fractions in which the elution solvent in the separation method 10 is methylene chloride: methanol mixing ratio 3: 1 and the elution solvent is methylene chloride: methanol mixture ratio 2: 1
  • the second to fourth of 4 fractions were separated under the conditions of the following separation method 11 through HPLC separation to separate the components of the fraction.
  • 1.6 mg of Compound B corresponding to Peak B of FIG. 4 24.8 mg of Compound R corresponding to Peak R of FIG. 4, 5.5 mg of Compound S corresponding to Peak S of FIG. 4, and corresponding to Peak T of FIG. 4.
  • Compound U corresponding to peak U of FIG. 4 9.3 mg
  • peak X of FIG. 0.6 mg of the corresponding compound X was isolated.
  • HPLC peaks corresponding to all the substances (Compounds 1 to 5, and Compounds C to X) separated in Examples 4 and 5 and Comparative Example 2 are as indicated for each peak of the named bud extract HPLC chromatogram in FIG. 4.
  • a total of 29 substances, including naphthopyrone derivatives having the structures of Formulas 1 to 5 (Compounds 1 to 5), are components that can be separated from the extract of the resulting shoot sprout obtained in Example 1.
  • the 29 substances correspond to the main component of the shoot sprout extract.
  • the molecular weight of Compound 1 isolated in Example 4 was determined to be 664 by MS measurement using an Agilent 1100 Fast Fluid Chromatography-Mass Spectrometer (HPLC-ESI-MS), ultraviolet (PerkinElmer 343 Polarimeter), infrared (Thermo Scientific).
  • Nicolet iS50 1 H and 13 C NMR spectrum analysis using non-photoluminescence (PerkinElmer Lambda 35) spectroscopy and nuclear magnetic resonance (Bruker 400 MHz, 100 MHz NMR) to obtain the structure of the formula
  • Eggplants were determined with 7-hydroxymusgininyl-rubrufusarin-8'-0-glucoside, a naphthopyrone derivative.
  • Compound 1 is a novel compound that has not been reported to date and has been isolated as one of the main components only in the shoot buds, which was not found or contained in very small amounts in the shooter or fully grown shooter plants.
  • the molecular weight of Compound 2 isolated in Example 5 was determined to be 272 by MS measurement using an Agilent 1100 High-Speed Fluid Chromatography-Mass Spectrometer (HPLC-ESI-MS), using a nuclear magnetic resonance analyzer (Bruker 400 MHz NMR). 1 H NMR spectra were used to estimate isotoractone, a naphthopyrone derivative having the structure shown in Formula 2 below. In addition, the structure of the NMR data was compared with that of the existing literature (Kitanaka, S. et al. Phytochemistry, 1981, 20, 1951-1953).
  • the molecular weight of Compound 3 isolated in Example 5 was determined to be 272 by MS measurement using an Agilent 1100 Fast Fluid Chromatography-Mass Spectrometer (HPLC-ESI-MS), using a nuclear magnetic resonance analyzer (Bruker 400 MHz NMR).
  • the structure was estimated by 1 H NMR spectral analysis as toralactone, a naphthopyrone derivative having the structure shown in Chemical Formula 3 below.
  • the structure of the NMR data was compared with that of the existing literature (Newman, AG et al. J Am Chem Soc 2016, 138, 4219-4228).
  • the molecular weight of Compound 4 isolated in Example 5 was determined to be 288 by MS measurement using an Agilent 1100 Fast Fluid Chromatography-Mass Spectrometer (HPLC-ESI-MS), using a nuclear magnetic resonance analyzer (Bruker 400 MHz NMR).
  • the structure was estimated by 1 H NMR spectral analysis as torosachrysone, a naphthopyron derivative having the structure shown in Chemical Formula 4 below.
  • the structure of the NMR data was compared with that of the existing literature (Gill, M. et al. Aust J Chem 2000, 53, 213-220).
  • the molecular weight of Compound 5 isolated in Example 5 was determined to be 288 by MS measurement using an Agilent 1100 High-Speed Fluid Chromatography-Mass Spectrometer (HPLC-ESI-MS), using a nuclear magnetic resonance analyzer (Bruker 400 MHz NMR). Through 1 H NMR spectroscopic analysis, the structure was estimated to be rubrofusarin, a naphthopyron derivative having the structure shown in Chemical Formula 5 below. In addition, the structure of NMR data was compared with that of the existing literature (Alemayehu, G. et al. Phytochemistry, 1993, 32, 1273-1277).
  • Dissolver extract (ST) prepared in Comparative Example 1 and the crystallized sprout extract (STS) prepared in Example 1 was dissolved in an aqueous solution of alcohol at the same concentration, according to the following analysis conditions ABTS online antioxidant high performance liquid chromatography (HPLC ) Was performed.
  • ABTS composition water containing 0.08 mM ABTS and 0.12 mM potassium persulfate
  • Detector detection wavelength ultraviolet 254 nm; 734 nm
  • Cassiae extract (ST) and Cassiae sprout extract (STS) showed very different antioxidant components.
  • the components of the Cassia vulgaris extract (ST) and Cassia vulgaris extract (STS) were found to be composed of flavonoids and naphthalene derivatives having sulfated activity 15 minutes before the retention time. At the same time as the contents of the above components were increased, naphthalene and anthraquinone derivatives having antioxidant activities were additionally observed after 15 minutes.
  • Figure 2 (A) and (B) is a result of performing the ABTS online antioxidant HPLC of the deficiency and the germinated bud extract, ultraviolet (UV) detector 254 nm (chromatic gram of the blue line indicated in the upward direction), 734 nm (downward) Chromatogram obtained by detecting wavelengths of red lines indicated by?).
  • UV detector 254 nm chromatic gram of the blue line indicated in the upward direction
  • 734 nm downward Chromatogram obtained by detecting wavelengths of red lines indicated by?
  • Clarified sprout extract prepared in Example 1 and Clarified sprout extract grown under various light conditions prepared in Example 2 (STS-C, STS-385, STS-465, STS-645 and STS-780) was dissolved in an aqueous alcohol solution, and subjected to ABTS online antioxidant high performance liquid chromatography (HPLC) according to the same analysis conditions as in Test Example 1.
  • HPLC high performance liquid chromatography
  • A, B, C, D, E, F of Figure 3 are ABTS online antioxidants of the six species of Sprout bud extracts STS, STS-C, STS-385, STS-465, STS-645 and STS-780, respectively.
  • the degree of antioxidant activity was determined by the area of the peaks and peaks of the UV detector 254 nm (showing peaks of the components absorbing UV 254 nm) and 734 nm wavelengths (antioxidative action against ABTS). It is a chromatogram obtained by detecting each).
  • Test Example 3 Example 7 kinds of 1 and 2 Fault Of sprout extract Retinal progenitor cells (R28) Protective effect
  • R28 cells at 37 ° C. in Dulbecco's modified eagle's medium (DMEM) / low glucose medium containing 10% fetal bovine serum (FBS), 100 U / mL penicillin, and 100 ⁇ g / mL streptomycin. After incubation under 5% CO 2 conditions in an incubator, passaged with 0.05% trypsin every 2 days, inoculated at a density of 1 ⁇ 10 4 in 96 plates and cultured for 24 hours. The 7 extracts were treated to the cultured R28 cells at the concentrations of (A) to (C) of FIG.
  • DMEM Dulbecco's modified eagle's medium
  • FBS fetal bovine serum
  • FIG 5 (A) is a light extract of Example 2, the extract of the crystallized shooter (ST) of the Comparative Example 1, ST extract of Example 1, at three concentrations from the oxidative stress caused by glutamate This is the result of the cell survival rate of the R28 cell protection effect of the five species of sprout sprouts cultivated differently (STS-C, STS-385, STS-465, STS-645, STS-780).
  • Figure 5 (B) and (C) are R28 cells of the clarifier extract (ST) of the Comparative Example 1 and the sprout bud extract (STS) of Example 1 from the oxidative stress caused by glutamate at each of five concentrations, respectively Protective efficacy is shown as cell viability.
  • Example 5 and 6 Fault Of compounds 1 to 5 isolated from sprout extract Retinal progenitor cells (R28) Confirmation of protective efficacy
  • Compounds 1 to 5 exhibited an effect of protecting R28 cells from neurotoxicity induced by glutamate, and the compounds have a relatively high content in the Sprout Sprout Extract (STS) or the Sprout Sprout Extract. Since the compounds are mainly present in (STS), it was confirmed that the R28 cell protective effect of the shoot sprout extract (STS) is superior to that of the shooter extract (ST).
  • Test Example 5 Example 7 kinds of 1 and 2 Fault Protective Effect of Sprout Extract on Hippocampal Neuronal Cells (HT-22)
  • HT-22 cells are 10% fetal bovine serum (FBS), 100 U / mL penicillin, and 100 ⁇ g / mL streptomycin containing DMEM (Dulbecco's modified eagle's medium), 5% in a 37.5 ° C incubator in low glucose medium. Incubated under CO 2 conditions, subcultured with 0.05% trypsin every 2 days, inoculated at a density of 3 ⁇ 10 3 in 96 plates and cultured for 24 hours. The 7 extracts were treated to the cultured HT-22 cells at the concentrations of (A) to (C) of FIG. 7, and 2 hours later, 5 mM glutamate was added and cultured for 22 hours. Then, 10 ⁇ L EZ-cytox was treated and maintained for 2 hours to measure cell viability, and UV absorbance was measured at 450 nm.
  • FBS fetal bovine serum
  • penicillin 100 U / mL penicillin
  • streptomycin containing DMEM Dulbecco
  • Figure 7 (A) is the light extract of Example 2, the extract of the glenja extract of Comparative Example 1 (ST), the shoot sprout of Example 1 (STS) at three concentrations from the oxidative stress caused by glutamate HT-22 cell protection effect of the five species of sprout sprouts (STS-C, STS-385, STS-465, STS-645, STS-780) cultivated differently to the cell survival rate.
  • Figure 7 (B) and (C) is HT-22 of the deficiency extract (ST) of the Comparative Example 1 and the deficiency sprout extract (STS) of Example 1 from the oxidative stress caused by glutamate at five concentrations It is the result of cell protection effect by cell viability.
  • HT-22 cell viability was measured in the same manner as in Test Example 5, Comparative Example 1, Example 1, Example 2 extract gyeongjab (ST), the shoot sprout extract (STS, STS-C, STS-385, STS-465 , STS-645 and STS-780) instead of compounds 1 to 5 of Examples 5 and 6 were treated with 50 ⁇ M, 16.6 ⁇ M, 5.55 ⁇ M, and the results are shown in FIG. 8.
  • Table 1 The physiological activity of each component evaluated in Test Example 1, Test Example 4 and Test Example 6 is shown in Table 1 below.
  • Table 1 below relates to the physiological activity of the components isolated from the bud extract (STS) of Example 1.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Neurosurgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • General Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention concerne un dérivé de naphtopyrone et une composition comprenant, en tant que principe actif, un extrait de pousses de Cassia obtusifolia, comprenant le dérivé de naphtopyrone. Selon un aspect, une composition fournie par la présente invention a un effet antioxydant et un effet de protection des neurones contre le stress oxydatif ou l'inhibition de la mort des neurones, et en particulier, a pour effet d'inhiber l'endommagement ou la mort de neurones rétiniens ou de neurones hippocampiques en raison de la toxicité du glutamate, et par conséquent la composition peut être utilisée en tant que composition pharmaceutique ou alimentaire pour le traitement ou la prévention de maladies oculaires et la détérioration et la perte de vision provoquées par une lésion nerveuse optique, et pour le traitement ou la prévention de la perte de mémoire, du déclin de la capacité d'apprentissage, de l'apparition et de l'aggravation de troubles dépressifs, et de maladies neurologiques dégénératives provoquées par des lésions nerveuses cérébrales.
PCT/KR2019/000399 2018-09-03 2019-01-10 Composition de protection des neurones comprenant un dérivé de naphtopyrone dérivé de pousses de cassia obtusifolia WO2020050462A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201980072747.9A CN112996799A (zh) 2018-09-03 2019-01-10 包含来源于决明子芽的萘并吡喃酮衍生物的神经细胞保护用组合物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020180104785A KR102121915B1 (ko) 2018-09-03 2018-09-03 결명 새싹 유래 나프토파이론 유도체를 포함하는 신경세포 보호용 조성물
KR10-2018-0104785 2018-09-03

Publications (1)

Publication Number Publication Date
WO2020050462A1 true WO2020050462A1 (fr) 2020-03-12

Family

ID=69723154

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2019/000399 WO2020050462A1 (fr) 2018-09-03 2019-01-10 Composition de protection des neurones comprenant un dérivé de naphtopyrone dérivé de pousses de cassia obtusifolia

Country Status (3)

Country Link
KR (1) KR102121915B1 (fr)
CN (1) CN112996799A (fr)
WO (1) WO2020050462A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220257974A1 (en) * 2019-11-06 2022-08-18 Industry Academic Cooperation Foundation Keimyung University Photobiomodulation method and system for inducing activity of brainderived nerve growth factor in hippocampal tissue

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102610332B1 (ko) * 2021-05-14 2023-12-07 농업회사법인 주식회사 넥스트온 생장이 증가되고 생리활성물질의 함량이 증가된 보리 또는 결명 새싹의 재배방법
KR20230082411A (ko) 2021-12-01 2023-06-08 주식회사 켐네이처 결명자새싹추출물 및 메밀새싹추출물을 포함하는 안구질환의 예방용 또는 치료용 혼합조성물 및 그 제조방법

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040044067A1 (en) * 2000-02-16 2004-03-04 Xiaodong Pan Toralactone and its derivation and the use of decreasing blood-fat and losing weight
US20080182803A1 (en) * 2002-05-31 2008-07-31 Suntory Limited Rubrofusarin glycoside-containing composition

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100877371B1 (ko) 2007-03-30 2009-01-09 주식회사 로제트 시력 보호용 조성물
KR101091596B1 (ko) 2009-01-08 2011-12-13 건국대학교 산학협력단 기능성 성분을 함유하는 당뇨 또는 당뇨 합병증의 예방 또는 치료 효능을 가지는 시력보호용 조성물
KR101503429B1 (ko) 2013-05-23 2015-03-18 한국식품연구원 볶음 처리를 이용한 항산화 활성이 증가된 결명자의 제조 방법
KR20160058613A (ko) 2014-11-17 2016-05-25 대한민국(농촌진흥청장) 새싹밀 추출물을 포함하는 항산화 조성물
KR101807367B1 (ko) 2015-11-30 2017-12-12 남서울대학교 산학협력단 브로콜리 새싹 추출물을 유효성분으로 함유하는 항산화 조성물 및 그의 제조방법

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040044067A1 (en) * 2000-02-16 2004-03-04 Xiaodong Pan Toralactone and its derivation and the use of decreasing blood-fat and losing weight
US20080182803A1 (en) * 2002-05-31 2008-07-31 Suntory Limited Rubrofusarin glycoside-containing composition

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DONG, X. ET AL.: "Cassiae semen: A review of its phytochemistry and pharmacology (Review)", MOLECULAR MEDICINE REPORTS, vol. 16, 2017, pages 2331 - 2346, XP055693248 *
SHRESTHA, S. ET AL.: "Structure Related Inhibition of Enzyme Systems in Choline sterases and BACE1 In Vitro by Naturally Occurring Naphthopyrone and Its Glycosides Isolated from Cassia obtusifolia", MOLECULES, vol. 23, 69, 28 December 2017 (2017-12-28), pages 1 - 17, XP055693252 *
TANG, L. ET AL.: "Four new glycosides from the seeds of Cassia obtusifolia", PHYTOCHEMISTRY LETTERS, vol. 13, 2015, pages 81 - 84, XP055693249 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220257974A1 (en) * 2019-11-06 2022-08-18 Industry Academic Cooperation Foundation Keimyung University Photobiomodulation method and system for inducing activity of brainderived nerve growth factor in hippocampal tissue

Also Published As

Publication number Publication date
KR102121915B1 (ko) 2020-06-11
KR20200026612A (ko) 2020-03-11
CN112996799A (zh) 2021-06-18

Similar Documents

Publication Publication Date Title
WO2020050462A1 (fr) Composition de protection des neurones comprenant un dérivé de naphtopyrone dérivé de pousses de cassia obtusifolia
WO2018124508A1 (fr) Composition pour la prévention et le traitement de maladies musculaires ou pour l'amélioration de la fonction musculaire, contenant de l'acide 3,5-dicaféoylquinique ou de l'extrait de chrysanthème
WO2021221405A1 (fr) Composition cosmétique fonctionnelle comprenant un extrait végétal comme principe actif et son procédé de préparation
WO2021137677A1 (fr) Composition contenant un extrait de plante
WO2009151302A9 (fr) Composition anti-âge ou anti-oxydation contenant des lignées de cellules souches végétales dérivées du cambium de panax ginseng comprenant du ginseng sauvage et du ginseng comme principes actifs
WO2017111211A1 (fr) Composition antioxydante comprenant un extrait de sargassum serratifolium ou un fragment de ce dernier en tant qu'ingrédient actif
WO2022035115A1 (fr) Composition pour la prévention et le traitement des troubles musculo–squelettiques contenant un extrait d'alnus japonica ou un composé isolé à partir de celui-ci et utilisation de celle-ci
WO2017123056A1 (fr) Nanocomposite comprenant un système d'administration de médicament nanométrique et extrait de ginseng ou ginsénoside séparé de celui-ci
WO2013183920A1 (fr) Composition pharmaceutique contenant un dérivé de verbénone pour le traitement ou la prévention d'une maladie neurodégénérative
WO2014175543A1 (fr) Composition pour prévenir, soulager ou traiter la colite, contenant des extraits complexes
WO2012067316A1 (fr) Composition pour la prévention ou le traitement de maladies métaboliques ou de complications de celles-ci contenant des composés à base de ptérocarpane ou des sels pharmaceutiquement acceptables de ceux-ci comme principe actif ou composition anti-oxydation
WO2012046945A2 (fr) Composition pharmaceutique et alimentaire pour la prévention ou le traitement du diabète ou de l'obésité
WO2012043949A1 (fr) Composition pour améliorer l'immunité contenant des composés représentés par les formules chimiques 1-8 ou l'extrait de sophora flavescens comme ingrédient actif
WO2018008803A1 (fr) Nouvelle utilisation d'un dérivé de sesquiterpène
WO2010090498A2 (fr) Composition pharmaceutique et composition d'aliment naturel contenant un extrait de youngia denticulata, une fraction de celui-ci, ou un composé isolé à partir de celui-ci en tant que substance active pour améliorer la fonction hépatique
WO2018062820A1 (fr) Composition visant à prévenir la chute des cheveux et à en favoriser la pousse, comprenant un phytoœstrogène en tant que principe actif
WO2014003232A1 (fr) Composition comprenant un extrait de dendropanax morbifera léveille en tant que principe actif pour la favorisation de la pousse des cheveux
KR102169240B1 (ko) 결명 새싹 유래 나프토파이론 유도체를 포함하는 신경세포 보호용 조성물
WO2018236186A1 (fr) Composition comprenant un dérivé de sesquiterpène en tant que principe actif pour la prévention ou le traitement de maladies musculaires
WO2012138146A9 (fr) Composition contenant de la poudre ou un extrait traité(e) thermiquement de glycine soja en tant qu'ingrédient actif destiné à la prévention et au traitement du diabète sucré et des complications du diabète
WO2016048085A1 (fr) Extrait dérivé de fève ayant des teneurs accrues en ingrédients actifs
WO2019027239A2 (fr) Composition pour prévenir la chute des cheveux ou stimuler la pousse des cheveux
WO2021015583A2 (fr) Procédé de préparation de feuille de soja ayant une teneur élevée en dérivé d'isoflavone dans des conditions d'obscurité et feuille de soja ayant une teneur élevée en dérivé d'isoflavone préparé au moyen de celui-ci
WO2018074880A2 (fr) Composition pharmaceutique de prévention ou de traitement de la pneumonie, comprenant un dérivé de quinolin-4-one ou un sel pharmaceutiquement acceptable associé en tant que principe actif
WO2022250322A1 (fr) Nouveau composé isolé à partir d'épinard, et composition le comprenant pour prévenir ou traiter des maladies inflammatoires

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19857439

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19857439

Country of ref document: EP

Kind code of ref document: A1