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 PDFInfo
- 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
Links
- JEUUNKOFKDUVMN-UHFFFAOYSA-N benzo[f]chromen-1-one Chemical class C1=CC=CC2=C3C(=O)C=COC3=CC=C21 JEUUNKOFKDUVMN-UHFFFAOYSA-N 0.000 title claims abstract description 126
- 239000000203 mixture Substances 0.000 title claims abstract description 101
- 244000277285 Cassia obtusifolia Species 0.000 title claims abstract description 46
- 235000006719 Cassia obtusifolia Nutrition 0.000 title claims abstract description 46
- 239000000284 extract Substances 0.000 claims abstract description 186
- 210000002569 neuron Anatomy 0.000 claims abstract description 85
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 61
- 229930195712 glutamate Natural products 0.000 claims abstract description 60
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 42
- 230000036542 oxidative stress Effects 0.000 claims abstract description 39
- 230000006378 damage Effects 0.000 claims abstract description 29
- 230000034994 death Effects 0.000 claims abstract description 19
- 235000013305 food Nutrition 0.000 claims abstract description 18
- 239000004480 active ingredient Substances 0.000 claims abstract description 16
- 230000002265 prevention Effects 0.000 claims abstract description 10
- 210000004295 hippocampal neuron Anatomy 0.000 claims abstract description 9
- 208000028389 Nerve injury Diseases 0.000 claims abstract description 8
- 230000008764 nerve damage Effects 0.000 claims abstract description 8
- 210000001116 retinal neuron Anatomy 0.000 claims abstract description 5
- 208000000044 Amnesia Diseases 0.000 claims abstract description 4
- 208000020401 Depressive disease Diseases 0.000 claims abstract description 4
- 208000026139 Memory disease Diseases 0.000 claims abstract description 4
- 230000007423 decrease Effects 0.000 claims abstract description 4
- 230000006984 memory degeneration Effects 0.000 claims abstract description 4
- 208000023060 memory loss Diseases 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims description 96
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 84
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 84
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 51
- 244000201986 Cassia tora Species 0.000 claims description 47
- 235000014552 Cassia tora Nutrition 0.000 claims description 46
- 239000012453 solvate Substances 0.000 claims description 41
- 150000004677 hydrates Chemical class 0.000 claims description 36
- 239000003963 antioxidant agent Substances 0.000 claims description 33
- 230000002207 retinal effect Effects 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 32
- 230000000971 hippocampal effect Effects 0.000 claims description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 20
- 239000000126 substance Substances 0.000 claims description 19
- 230000016273 neuron death Effects 0.000 claims description 18
- 206010029350 Neurotoxicity Diseases 0.000 claims description 16
- 206010044221 Toxic encephalopathy Diseases 0.000 claims description 16
- 230000007135 neurotoxicity Effects 0.000 claims description 16
- 231100000228 neurotoxicity Toxicity 0.000 claims description 16
- 230000004224 protection Effects 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 239000012046 mixed solvent Substances 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- 238000004587 chromatography analysis Methods 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 239000002038 ethyl acetate fraction Substances 0.000 claims description 7
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- 208000027418 Wounds and injury Diseases 0.000 claims description 5
- 230000005779 cell damage Effects 0.000 claims description 5
- 208000037887 cell injury Diseases 0.000 claims description 5
- 239000000469 ethanolic extract Substances 0.000 claims description 5
- 230000000926 neurological effect Effects 0.000 claims description 5
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 206010038848 Retinal detachment Diseases 0.000 claims description 3
- 230000002490 cerebral effect Effects 0.000 claims description 3
- 230000000302 ischemic effect Effects 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 230000004264 retinal detachment Effects 0.000 claims description 3
- 208000032400 Retinal pigmentation Diseases 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 210000000078 claw Anatomy 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
- 206010038903 Retinal vascular occlusion Diseases 0.000 claims 1
- 239000002032 methanolic fraction Substances 0.000 claims 1
- 208000015891 sexual disease Diseases 0.000 claims 1
- 230000001629 suppression Effects 0.000 claims 1
- 230000004304 visual acuity Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 20
- 230000002401 inhibitory effect Effects 0.000 abstract description 19
- 230000001988 toxicity Effects 0.000 abstract description 10
- 231100000419 toxicity Toxicity 0.000 abstract description 10
- 210000004556 brain Anatomy 0.000 abstract description 8
- 208000012902 Nervous system disease Diseases 0.000 abstract description 4
- 208000025966 Neurological disease Diseases 0.000 abstract description 4
- 201000004569 Blindness Diseases 0.000 abstract description 3
- 230000006866 deterioration Effects 0.000 abstract description 3
- 208000030533 eye disease Diseases 0.000 abstract description 3
- 230000003412 degenerative effect Effects 0.000 abstract description 2
- 230000004393 visual impairment Effects 0.000 abstract description 2
- 208000030768 Optic nerve injury Diseases 0.000 abstract 1
- 208000018769 loss of vision Diseases 0.000 abstract 1
- 231100000864 loss of vision Toxicity 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 76
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 42
- 210000004027 cell Anatomy 0.000 description 40
- 238000000926 separation method Methods 0.000 description 33
- 235000006708 antioxidants Nutrition 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- 230000000052 comparative effect Effects 0.000 description 24
- 241000196324 Embryophyta Species 0.000 description 23
- 238000012360 testing method Methods 0.000 description 23
- 238000000605 extraction Methods 0.000 description 22
- 238000004128 high performance liquid chromatography Methods 0.000 description 22
- 230000002829 reductive effect Effects 0.000 description 18
- 230000001681 protective effect Effects 0.000 description 16
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 15
- 201000010099 disease Diseases 0.000 description 15
- 239000012156 elution solvent Substances 0.000 description 14
- 238000010828 elution Methods 0.000 description 13
- 238000010992 reflux Methods 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 10
- 230000036541 health Effects 0.000 description 10
- 210000001320 hippocampus Anatomy 0.000 description 10
- 238000002955 isolation Methods 0.000 description 10
- 238000002156 mixing Methods 0.000 description 10
- 230000007812 deficiency Effects 0.000 description 9
- 210000001164 retinal progenitor cell Anatomy 0.000 description 9
- 238000004007 reversed phase HPLC Methods 0.000 description 9
- 230000003833 cell viability Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- WEHXAEGTVPWKDY-UHFFFAOYSA-N toralactone Chemical compound C1=C(C)OC(=O)C=2C1=CC1=CC(OC)=CC(O)=C1C=2O WEHXAEGTVPWKDY-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- -1 lactone glycosides Chemical class 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 210000001328 optic nerve Anatomy 0.000 description 7
- 239000003642 reactive oxygen metabolite Substances 0.000 description 7
- 210000001525 retina Anatomy 0.000 description 7
- 210000003994 retinal ganglion cell Anatomy 0.000 description 7
- BFMIUBHJKFRWIV-UHFFFAOYSA-N 3,8,9-trihydroxy-6-methoxy-3-methyl-2,4-dihydroanthracen-1-one Chemical compound O=C1CC(C)(O)CC2=CC3=CC(OC)=CC(O)=C3C(O)=C21 BFMIUBHJKFRWIV-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 6
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 238000000039 preparative column chromatography Methods 0.000 description 6
- 244000037364 Cinnamomum aromaticum Species 0.000 description 5
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 description 5
- 239000000287 crude extract Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000007760 free radical scavenging Effects 0.000 description 5
- 238000005286 illumination Methods 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- GEZBDPPVXYFNMG-UHFFFAOYSA-N 9,10-dihydroxy-7-methoxy-3-methylidene-4h-benzo[g]isochromen-1-one Chemical compound O=C1OC(=C)CC2=CC3=CC(OC)=CC(O)=C3C(O)=C21 GEZBDPPVXYFNMG-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229940125782 compound 2 Drugs 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 238000007598 dipping method Methods 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000208340 Araliaceae Species 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 3
- 235000003140 Panax quinquefolius Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000002964 excitative effect Effects 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 235000013376 functional food Nutrition 0.000 description 3
- 235000008434 ginseng Nutrition 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- FPNKCZKRICBAKG-UHFFFAOYSA-N rubrofusarin Chemical compound O1C(C)=CC(=O)C=2C1=CC1=CC(OC)=CC(O)=C1C=2O FPNKCZKRICBAKG-UHFFFAOYSA-N 0.000 description 3
- KLKFLNXANXGSIT-UHFFFAOYSA-N rubrofusarin Natural products O1C(C)=CC(=O)C2=C1C=C1C=C(O)C=C(OC)C1=C2O KLKFLNXANXGSIT-UHFFFAOYSA-N 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 0.000 description 2
- 239000004606 Fillers/Extenders Substances 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- 102000018899 Glutamate Receptors Human genes 0.000 description 2
- 108010027915 Glutamate Receptors Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000017170 Lipid metabolism disease Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical class C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- KJQFBVYMGADDTQ-UHFFFAOYSA-N S-butyl-DL-homocysteine (S,R)-sulfoximine Chemical compound CCCCS(=N)(=O)CCC(N)C(O)=O KJQFBVYMGADDTQ-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 108010021119 Trichosanthin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 210000000411 amacrine cell Anatomy 0.000 description 2
- 150000004056 anthraquinones Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000004958 brain cell Anatomy 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 235000013736 caramel Nutrition 0.000 description 2
- 230000034303 cell budding Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 230000004452 decreased vision Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000000105 evaporative light scattering detection Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 230000004438 eyesight Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 230000035784 germination Effects 0.000 description 2
- 239000006481 glucose medium Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 210000002287 horizontal cell Anatomy 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000004065 mitochondrial dysfunction Effects 0.000 description 2
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
- 231100000189 neurotoxic Toxicity 0.000 description 2
- 230000002887 neurotoxic effect Effects 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 235000003170 nutritional factors Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000006201 parenteral dosage form Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 230000009894 physiological stress Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 150000003138 primary alcohols Chemical class 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010183 spectrum analysis Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000003956 synaptic plasticity Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 210000003478 temporal lobe Anatomy 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
- 102000003678 AMPA Receptors Human genes 0.000 description 1
- 108090000078 AMPA Receptors Proteins 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- LTPIXWMMOLSQRG-UHFFFAOYSA-N CC(c(c(C)c(c1c2c(OC(C(C3O)O)OC(CO)C3O)cc(O)c1)-c(c(OC)cc1cc(OC(C)=CC3=O)c3c(O)c11)c1O)c2O)=O Chemical compound CC(c(c(C)c(c1c2c(OC(C(C3O)O)OC(CO)C3O)cc(O)c1)-c(c(OC)cc1cc(OC(C)=CC3=O)c3c(O)c11)c1O)c2O)=O LTPIXWMMOLSQRG-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 235000006693 Cassia laevigata Nutrition 0.000 description 1
- 102000003914 Cholinesterases Human genes 0.000 description 1
- 108090000322 Cholinesterases Proteins 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 102000005915 GABA Receptors Human genes 0.000 description 1
- 108010005551 GABA Receptors Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101000878457 Macrocallista nimbosa FMRFamide Proteins 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 244000184734 Pyrus japonica Species 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 235000004789 Rosa xanthina Nutrition 0.000 description 1
- 241000220222 Rosaceae Species 0.000 description 1
- 241000522641 Senna Species 0.000 description 1
- 244000061458 Solanum melongena Species 0.000 description 1
- 235000002597 Solanum melongena Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- ZMZINYUKVRMNTG-UHFFFAOYSA-N acetic acid;formic acid Chemical compound OC=O.CC(O)=O ZMZINYUKVRMNTG-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 210000004727 amygdala Anatomy 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Chemical class CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 230000004094 calcium homeostasis Effects 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000002380 cytological effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000036576 dermal application Effects 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
- ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 230000037427 ion transport Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000006993 memory improvement Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 238000000874 microwave-assisted extraction Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NCAIGTHBQTXTLR-UHFFFAOYSA-N phentermine hydrochloride Chemical compound [Cl-].CC(C)([NH3+])CC1=CC=CC=C1 NCAIGTHBQTXTLR-UHFFFAOYSA-N 0.000 description 1
- 230000008832 photodamage Effects 0.000 description 1
- 238000005424 photoluminescence Methods 0.000 description 1
- 210000000608 photoreceptor cell Anatomy 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 229940124513 senna glycoside Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
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)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Botany (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Mycology (AREA)
- Neurosurgery (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Neurology (AREA)
- Ophthalmology & Optometry (AREA)
- General Engineering & Computer Science (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.
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)
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)
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)
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)
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 |
-
2018
- 2018-09-03 KR KR1020180104785A patent/KR102121915B1/ko active IP Right Grant
-
2019
- 2019-01-10 WO PCT/KR2019/000399 patent/WO2020050462A1/fr active Application Filing
- 2019-01-10 CN CN201980072747.9A patent/CN112996799A/zh active Pending
Patent Citations (2)
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)
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)
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 |
CN112996799A (zh) | 2021-06-18 |
KR20200026612A (ko) | 2020-03-11 |
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 | |
WO2020235932A1 (fr) | Nouveau composé peptidique ou sel pharmaceutiquement acceptable 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 | |
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 | |
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 | |
WO2017052227A1 (fr) | Composition pour la prévention ou le traitement d'une maladie du nerf crânien comprenant un extrait d'amadouvier, sa fraction ou un composé isolé à partir de celui-ci en tant que principe actif |
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 |