JP5785546B2 - 脳虚血を予防または処置する方法 - Google Patents
脳虚血を予防または処置する方法 Download PDFInfo
- Publication number
- JP5785546B2 JP5785546B2 JP2012526918A JP2012526918A JP5785546B2 JP 5785546 B2 JP5785546 B2 JP 5785546B2 JP 2012526918 A JP2012526918 A JP 2012526918A JP 2012526918 A JP2012526918 A JP 2012526918A JP 5785546 B2 JP5785546 B2 JP 5785546B2
- Authority
- JP
- Japan
- Prior art keywords
- composition
- tocotrienol quinone
- subject
- cerebral
- cerebral ischemic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 206010008118 cerebral infarction Diseases 0.000 title claims description 38
- 238000000034 method Methods 0.000 title description 110
- 201000006474 Brain Ischemia Diseases 0.000 title description 30
- 206010008120 Cerebral ischaemia Diseases 0.000 title description 29
- 239000000203 mixture Substances 0.000 claims description 182
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 146
- 230000000302 ischemic effect Effects 0.000 claims description 96
- 230000002490 cerebral effect Effects 0.000 claims description 92
- LNOVHERIIMJMDG-KTWAZNHYSA-N 2-[(6e,10e)-3-hydroxy-3,7,11,15-tetramethylhexadeca-6,10,14-trienyl]-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CCC(C)(O)CCC1=C(C)C(=O)C(C)=C(C)C1=O LNOVHERIIMJMDG-KTWAZNHYSA-N 0.000 claims description 84
- 150000001875 compounds Chemical class 0.000 claims description 73
- 208000006011 Stroke Diseases 0.000 claims description 52
- 229930003802 tocotrienol Natural products 0.000 claims description 52
- 239000011731 tocotrienol Substances 0.000 claims description 52
- 235000019148 tocotrienols Nutrition 0.000 claims description 52
- GJJVAFUKOBZPCB-UHFFFAOYSA-N 2-methyl-2-(4,8,12-trimethyltrideca-3,7,11-trienyl)-3,4-dihydrochromen-6-ol Chemical compound OC1=CC=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1 GJJVAFUKOBZPCB-UHFFFAOYSA-N 0.000 claims description 47
- 238000011282 treatment Methods 0.000 claims description 43
- 208000024891 symptom Diseases 0.000 claims description 32
- 208000028389 Nerve injury Diseases 0.000 claims description 28
- 230000008764 nerve damage Effects 0.000 claims description 28
- 208000012268 mitochondrial disease Diseases 0.000 claims description 22
- RZFHLOLGZPDCHJ-DLQZEEBKSA-N alpha-Tocotrienol Natural products Oc1c(C)c(C)c2O[C@@](CC/C=C(/CC/C=C(\CC/C=C(\C)/C)/C)\C)(C)CCc2c1C RZFHLOLGZPDCHJ-DLQZEEBKSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 230000037396 body weight Effects 0.000 claims description 17
- FGYKUFVNYVMTAM-UHFFFAOYSA-N (R)-2,5,8-trimethyl-2-(4,8,12-trimethyl-trideca-3t,7t,11-trienyl)-chroman-6-ol Natural products OC1=CC(C)=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1C FGYKUFVNYVMTAM-UHFFFAOYSA-N 0.000 claims description 13
- SFVAYPRWECRHTF-QRCIITMISA-N 2-[(6e,10e)-3-hydroxy-3,7,11,15-tetramethylhexadeca-6,10,14-trienyl]-6-methylcyclohexa-2,5-diene-1,4-dione Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CCC(C)(O)CCC1=CC(=O)C=C(C)C1=O SFVAYPRWECRHTF-QRCIITMISA-N 0.000 claims description 13
- FGYKUFVNYVMTAM-YMCDKREISA-N beta-Tocotrienol Natural products Oc1c(C)c2c(c(C)c1)O[C@@](CC/C=C(\CC/C=C(\CC/C=C(\C)/C)/C)/C)(C)CC2 FGYKUFVNYVMTAM-YMCDKREISA-N 0.000 claims description 13
- 230000001120 cytoprotective effect Effects 0.000 claims description 13
- FGYKUFVNYVMTAM-MUUNZHRXSA-N epsilon-Tocopherol Natural products OC1=CC(C)=C2O[C@@](CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1C FGYKUFVNYVMTAM-MUUNZHRXSA-N 0.000 claims description 13
- 235000019151 β-tocotrienol Nutrition 0.000 claims description 13
- 239000011723 β-tocotrienol Substances 0.000 claims description 13
- FGYKUFVNYVMTAM-WAZJVIJMSA-N β-tocotrienol Chemical compound OC1=CC(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1C FGYKUFVNYVMTAM-WAZJVIJMSA-N 0.000 claims description 13
- OTXNTMVVOOBZCV-UHFFFAOYSA-N 2R-gamma-tocotrienol Natural products OC1=C(C)C(C)=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1 OTXNTMVVOOBZCV-UHFFFAOYSA-N 0.000 claims description 12
- OTXNTMVVOOBZCV-YMCDKREISA-N gamma-Tocotrienol Natural products Oc1c(C)c(C)c2O[C@@](CC/C=C(\CC/C=C(\CC/C=C(\C)/C)/C)/C)(C)CCc2c1 OTXNTMVVOOBZCV-YMCDKREISA-N 0.000 claims description 12
- 235000019150 γ-tocotrienol Nutrition 0.000 claims description 12
- 239000011722 γ-tocotrienol Substances 0.000 claims description 12
- OTXNTMVVOOBZCV-WAZJVIJMSA-N γ-tocotrienol Chemical compound OC1=C(C)C(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1 OTXNTMVVOOBZCV-WAZJVIJMSA-N 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 206010030113 Oedema Diseases 0.000 claims description 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- 210000005013 brain tissue Anatomy 0.000 claims description 8
- 208000010877 cognitive disease Diseases 0.000 claims description 8
- 210000005166 vasculature Anatomy 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 208000037906 ischaemic injury Diseases 0.000 claims description 6
- 230000016273 neuron death Effects 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 206010047163 Vasospasm Diseases 0.000 claims description 4
- 230000000740 bleeding effect Effects 0.000 claims description 4
- 230000002612 cardiopulmonary effect Effects 0.000 claims description 4
- 208000010496 Heart Arrest Diseases 0.000 claims description 2
- 239000008177 pharmaceutical agent Substances 0.000 claims description 2
- 206010061216 Infarction Diseases 0.000 description 33
- 230000007574 infarction Effects 0.000 description 33
- 210000004556 brain Anatomy 0.000 description 31
- 210000004027 cell Anatomy 0.000 description 28
- 230000006378 damage Effects 0.000 description 26
- 208000014674 injury Diseases 0.000 description 25
- 208000027418 Wounds and injury Diseases 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
- 239000002609 medium Substances 0.000 description 20
- 230000002265 prevention Effects 0.000 description 18
- 201000010099 disease Diseases 0.000 description 17
- 206010021143 Hypoxia Diseases 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 208000028867 ischemia Diseases 0.000 description 16
- 239000003814 drug Substances 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 14
- 230000001537 neural effect Effects 0.000 description 14
- 229910052760 oxygen Inorganic materials 0.000 description 14
- 239000001301 oxygen Substances 0.000 description 14
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- -1 ruberzole Chemical class 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 230000010410 reperfusion Effects 0.000 description 12
- 238000009472 formulation Methods 0.000 description 11
- 239000008194 pharmaceutical composition Substances 0.000 description 11
- 230000017531 blood circulation Effects 0.000 description 10
- 235000013305 food Nutrition 0.000 description 10
- 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 10
- 239000003981 vehicle Substances 0.000 description 10
- 206010008089 Cerebral artery occlusion Diseases 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000012981 Hank's balanced salt solution Substances 0.000 description 9
- 230000007954 hypoxia Effects 0.000 description 9
- 238000003384 imaging method Methods 0.000 description 9
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 9
- 238000001356 surgical procedure Methods 0.000 description 9
- 238000003556 assay Methods 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 230000006872 improvement Effects 0.000 description 8
- 230000003902 lesion Effects 0.000 description 8
- 239000002502 liposome Substances 0.000 description 8
- 238000002595 magnetic resonance imaging Methods 0.000 description 8
- 238000002600 positron emission tomography Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 230000030833 cell death Effects 0.000 description 7
- 208000026106 cerebrovascular disease Diseases 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 235000004835 α-tocopherol Nutrition 0.000 description 7
- 239000002076 α-tocopherol Substances 0.000 description 7
- 208000032382 Ischaemic stroke Diseases 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 229940087168 alpha tocopherol Drugs 0.000 description 6
- 229940064063 alpha tocotrienol Drugs 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 238000002597 diffusion-weighted imaging Methods 0.000 description 6
- 210000001320 hippocampus Anatomy 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000002195 synergetic effect Effects 0.000 description 6
- 229960000984 tocofersolan Drugs 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- RZFHLOLGZPDCHJ-XZXLULOTSA-N α-Tocotrienol Chemical compound OC1=C(C)C(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1C RZFHLOLGZPDCHJ-XZXLULOTSA-N 0.000 description 6
- 235000019145 α-tocotrienol Nutrition 0.000 description 6
- 239000011730 α-tocotrienol Substances 0.000 description 6
- WGVKWNUPNGFDFJ-DQCZWYHMSA-N β-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C WGVKWNUPNGFDFJ-DQCZWYHMSA-N 0.000 description 6
- 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 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 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 5
- SBHDKYTVDCRMOE-JPAPVDFESA-L copper;n'-methyl-n-[(e)-[(3e)-3-[(n-methyl-c-sulfidocarbonimidoyl)hydrazinylidene]butan-2-ylidene]amino]carbamimidothioate Chemical compound [Cu+2].CN=C([S-])N\N=C(/C)\C(\C)=N\NC([S-])=NC SBHDKYTVDCRMOE-JPAPVDFESA-L 0.000 description 5
- 235000015872 dietary supplement Nutrition 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000006187 pill Substances 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 229960005322 streptomycin Drugs 0.000 description 5
- 230000001629 suppression Effects 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- ZCXUVYAZINUVJD-AHXZWLDOSA-N 2-deoxy-2-((18)F)fluoro-alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H]([18F])[C@@H](O)[C@@H]1O ZCXUVYAZINUVJD-AHXZWLDOSA-N 0.000 description 4
- 208000028698 Cognitive impairment Diseases 0.000 description 4
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 229930182816 L-glutamine Natural products 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 4
- 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 4
- 238000002399 angioplasty Methods 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 230000000971 hippocampal effect Effects 0.000 description 4
- 230000001146 hypoxic effect Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 210000003657 middle cerebral artery Anatomy 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 229940049954 penicillin Drugs 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 239000008159 sesame oil Substances 0.000 description 4
- 235000011803 sesame oil Nutrition 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000013589 supplement Substances 0.000 description 4
- 238000003325 tomography Methods 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- GZIFEOYASATJEH-VHFRWLAGSA-N δ-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-VHFRWLAGSA-N 0.000 description 4
- 238000010176 18-FDG-positron emission tomography Methods 0.000 description 3
- 208000030090 Acute Disease Diseases 0.000 description 3
- 206010003497 Asphyxia Diseases 0.000 description 3
- 208000005189 Embolism Diseases 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 208000032109 Transient ischaemic attack Diseases 0.000 description 3
- 229930003427 Vitamin E Natural products 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000036770 blood supply Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000002405 diagnostic procedure Methods 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229940049906 glutamate Drugs 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 230000004217 heart function Effects 0.000 description 3
- 230000002008 hemorrhagic effect Effects 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000003961 neuronal insult Effects 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000700 radioactive tracer Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 229930003799 tocopherol Natural products 0.000 description 3
- 239000011732 tocopherol Substances 0.000 description 3
- 201000010875 transient cerebral ischemia Diseases 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- 235000007680 β-tocopherol Nutrition 0.000 description 3
- 239000011590 β-tocopherol Substances 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
- GJJVAFUKOBZPCB-ZGRPYONQSA-N (r)-3,4-dihydro-2-methyl-2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-2h-1-benzopyran-6-ol Chemical class OC1=CC=C2OC(CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1 GJJVAFUKOBZPCB-ZGRPYONQSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- IPJDHSYCSQAODE-UHFFFAOYSA-N 5-chloromethylfluorescein diacetate Chemical compound O1C(=O)C2=CC(CCl)=CC=C2C21C1=CC=C(OC(C)=O)C=C1OC1=CC(OC(=O)C)=CC=C21 IPJDHSYCSQAODE-UHFFFAOYSA-N 0.000 description 2
- 206010002660 Anoxia Diseases 0.000 description 2
- 239000012583 B-27 Supplement Substances 0.000 description 2
- 206010048962 Brain oedema Diseases 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
- GZIFEOYASATJEH-UHFFFAOYSA-N D-delta tocopherol Natural products OC1=CC(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 208000035177 MELAS Diseases 0.000 description 2
- 201000009906 Meningitis Diseases 0.000 description 2
- 206010073734 Microembolism Diseases 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
- 206010028851 Necrosis Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- 206010047139 Vasoconstriction Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000004103 aerobic respiration Effects 0.000 description 2
- 229940025084 amphetamine Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000002583 angiography Methods 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229940066595 beta tocopherol Drugs 0.000 description 2
- 208000006752 brain edema Diseases 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000003727 cerebral blood flow Effects 0.000 description 2
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229960003920 cocaine Drugs 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000002301 combined effect Effects 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 235000010389 delta-tocopherol Nutrition 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000002296 eclampsia Diseases 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000004153 glucose metabolism Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000007917 intracranial administration Methods 0.000 description 2
- 208000001286 intracranial vasospasm Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 210000002418 meninge Anatomy 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 210000002243 primary neuron Anatomy 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000002633 protecting effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 210000003625 skull Anatomy 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 208000006379 syphilis Diseases 0.000 description 2
- IDELNEDBPWKHGK-UHFFFAOYSA-N thiobutabarbital Chemical compound CCC(C)C1(CC)C(=O)NC(=S)NC1=O IDELNEDBPWKHGK-UHFFFAOYSA-N 0.000 description 2
- 125000002640 tocopherol group Chemical class 0.000 description 2
- 235000019149 tocopherols Nutrition 0.000 description 2
- 229940068778 tocotrienols Drugs 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000025033 vasoconstriction Effects 0.000 description 2
- 210000002385 vertebral artery Anatomy 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000002446 δ-tocopherol Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 125000005926 1,2-dimethylbutyloxy group Chemical group 0.000 description 1
- UTPYTEWRMXITIN-YDWXAUTNSA-N 1-methyl-3-[(e)-[(3e)-3-(methylcarbamothioylhydrazinylidene)butan-2-ylidene]amino]thiourea Chemical compound CNC(=S)N\N=C(/C)\C(\C)=N\NC(=S)NC UTPYTEWRMXITIN-YDWXAUTNSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 206010060874 Aortic rupture Diseases 0.000 description 1
- 102000011730 Arachidonate 12-Lipoxygenase Human genes 0.000 description 1
- 108010076676 Arachidonate 12-lipoxygenase Proteins 0.000 description 1
- 208000022211 Arteriovenous Malformations Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 208000001408 Carbon monoxide poisoning Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 208000022306 Cerebral injury Diseases 0.000 description 1
- 206010059109 Cerebral vasoconstriction Diseases 0.000 description 1
- 244000060011 Cocos nucifera Species 0.000 description 1
- 235000013162 Cocos nucifera Nutrition 0.000 description 1
- 208000029147 Collagen-vascular disease Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 206010013647 Drowning Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 206010014498 Embolic stroke Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 206010058279 Factor V Leiden mutation Diseases 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 206010018985 Haemorrhage intracranial Diseases 0.000 description 1
- 206010019013 Haemorrhagic infarction Diseases 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000008574 Intracranial Hemorrhages Diseases 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
- 102100037611 Lysophospholipase Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 description 1
- 201000002169 Mitochondrial myopathy Diseases 0.000 description 1
- 208000009433 Moyamoya Disease Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 208000008601 Polycythemia Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102000001332 SRC Human genes 0.000 description 1
- 108060006706 SRC Proteins 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 229940123182 Superoxide dismutase inhibitor Drugs 0.000 description 1
- 208000001106 Takayasu Arteritis Diseases 0.000 description 1
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 1
- 208000005485 Thrombocytosis Diseases 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 206010063661 Vascular encephalopathy Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000007950 acidosis Effects 0.000 description 1
- 208000026545 acidosis disease Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 210000004712 air sac Anatomy 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000004099 anaerobic respiration Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 230000005744 arteriovenous malformation Effects 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- RYGMFSIKBFXOCR-YPZZEJLDSA-N copper-62 Chemical compound [62Cu] RYGMFSIKBFXOCR-YPZZEJLDSA-N 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000003073 embolic effect Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 150000002148 esters Chemical class 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
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 208000008487 fibromuscular dysplasia Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000002795 fluorescence method Methods 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 235000010382 gamma-tocopherol Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 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
- 238000007429 general method Methods 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000004295 hippocampal neuron Anatomy 0.000 description 1
- 235000006486 human diet Nutrition 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000023692 inborn mitochondrial myopathy Diseases 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 208000021267 infertility disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000006443 lactic acidosis Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 230000008338 local blood flow Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000027928 long-term synaptic potentiation Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 235000020879 medical diet Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000003557 neuropsychological effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 230000007959 normoxia Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000004783 oxidative metabolism Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000001176 projection neuron Anatomy 0.000 description 1
- 210000002763 pyramidal cell Anatomy 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 208000004124 rheumatic heart disease Diseases 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000003977 synaptic function Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229920001059 synthetic polymer Polymers 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
- 235000012222 talc Nutrition 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229940026152 thiobutabarbital Drugs 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 238000012285 ultrasound imaging Methods 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000003966 vascular damage Effects 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 125000001020 α-tocopherol group Chemical group 0.000 description 1
- 239000002478 γ-tocopherol Substances 0.000 description 1
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27526909P | 2009-08-26 | 2009-08-26 | |
| US61/275,269 | 2009-08-26 | ||
| PCT/US2010/046503 WO2011025785A1 (en) | 2009-08-26 | 2010-08-24 | Methods for the prevention and treatment of cerebral ischemia |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015027506A Division JP2015091899A (ja) | 2009-08-26 | 2015-02-16 | 脳虚血を予防または処置する方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013503168A JP2013503168A (ja) | 2013-01-31 |
| JP2013503168A5 JP2013503168A5 (enExample) | 2013-10-10 |
| JP5785546B2 true JP5785546B2 (ja) | 2015-09-30 |
Family
ID=42983642
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012526918A Expired - Fee Related JP5785546B2 (ja) | 2009-08-26 | 2010-08-24 | 脳虚血を予防または処置する方法 |
| JP2015027506A Pending JP2015091899A (ja) | 2009-08-26 | 2015-02-16 | 脳虚血を予防または処置する方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015027506A Pending JP2015091899A (ja) | 2009-08-26 | 2015-02-16 | 脳虚血を予防または処置する方法 |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US20110207828A1 (enExample) |
| EP (1) | EP2470168B1 (enExample) |
| JP (2) | JP5785546B2 (enExample) |
| CN (1) | CN102647981B (enExample) |
| AU (1) | AU2010286704B2 (enExample) |
| BR (1) | BR112012004167A2 (enExample) |
| CA (1) | CA2772294C (enExample) |
| DK (1) | DK2470168T3 (enExample) |
| EA (1) | EA028677B1 (enExample) |
| ES (1) | ES2663709T3 (enExample) |
| HU (1) | HUE037592T2 (enExample) |
| MX (1) | MX337990B (enExample) |
| NO (1) | NO2470168T3 (enExample) |
| PL (1) | PL2470168T3 (enExample) |
| PT (1) | PT2470168T (enExample) |
| SI (1) | SI2470168T1 (enExample) |
| WO (1) | WO2011025785A1 (enExample) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2583087C (en) | 2003-09-19 | 2012-07-10 | Galileo Pharmaceuticals, Inc. | Chroman derivatives |
| WO2006130775A2 (en) * | 2005-06-01 | 2006-12-07 | Edison Pharmaceuticals, Inc. | Redox-active therapeutics for treatment of mitochondrial diseases and other conditions and modulation of energy biomakers |
| JP5374162B2 (ja) | 2006-02-22 | 2013-12-25 | エジソン ファーマシューティカルズ， インコーポレイテッド | ミトコンドリア病および他の症状の処置のためのレドックス活性化治療の側鎖変異体およびエネルギーバイオマーカーの調節 |
| EP3456707B1 (en) | 2007-11-06 | 2020-04-15 | PTC Therapeutics, Inc. | 4- (p-quinonyl)-2-hydroxybutanamide derivatives for treatment of mitochondrial diseases |
| EA023618B1 (ru) | 2008-01-08 | 2016-06-30 | Эдисон Фармасьютикалз, Инк. | Производные (гет)арил-п-хинона для лечения митохондриальных болезней |
| CA2717734A1 (en) | 2008-03-05 | 2009-09-11 | Edison Pharmaceuticals, Inc | 2-substituted-p-quinone derivatives for treatment of oxidative stress diseases |
| WO2009158348A1 (en) * | 2008-06-25 | 2009-12-30 | Edison Pharmaceuticals, Inc. | 2-heterocyclylaminoalkyl-(p-quinone) derivatives for treatment of oxidative stress diseases |
| EP3827815B1 (en) | 2008-09-10 | 2023-09-06 | PTC Therapeutics, Inc. | Treatment of pervasive developmental disorders with redox-active therapeutics |
| WO2010045220A1 (en) | 2008-10-14 | 2010-04-22 | Edison Pharmaceuticals, Inc. | Treatment of oxidative stress disorders including contrast nephropathy, radiation damage and disruptions in the function of red cells |
| TR201819154T4 (tr) | 2008-10-28 | 2019-01-21 | Bioelectron Tech Corp | Alfa-tokotrienol kuinone ve ara ürünlerini içeren bileşim. |
| WO2010126911A1 (en) | 2009-04-28 | 2010-11-04 | Edison Pharmaceuticals, Inc. | Treatment of leber's hereditary optic neuropathy and dominant optic atrophy with tocotrienol quinones |
| EP2519232A1 (en) * | 2009-12-31 | 2012-11-07 | Edison Pharmaceuticals, Inc. | Treatment of leigh syndrome and leigh-like syndrome with tocotrienol quinones |
| AU2011245384C1 (en) * | 2010-04-27 | 2016-09-01 | Bioelectron Technology Corporation | Formulations of quinones for the treatment of ophthalmic diseases |
| LT2680873T (lt) | 2011-03-03 | 2017-11-27 | Cidara Therapeutics, Inc. | Priešgrybeliniai agentai ir jų panaudojimas |
| US9464016B2 (en) | 2011-06-14 | 2016-10-11 | Edison Pharmaceuticals, Inc. | Catechol derivatives for treatment of oxidative stress diseases |
| JP2014520894A (ja) | 2011-07-19 | 2014-08-25 | エジソン ファーマシューティカルズ， インコーポレイテッド | 非アルファトコトリエノールの存在下でのアルファトコトリエノールの選択的酸化のための方法 |
| GB201117808D0 (en) * | 2011-10-14 | 2011-11-30 | Siemens Medical Solutions | SUV correction following dose infiltration |
| KR102236462B1 (ko) * | 2012-03-19 | 2021-04-08 | 시다라 세라퓨틱스, 인코포레이티드 | 에키노칸딘 계열의 화합물에 대한 투여 용법 |
| CA2883882A1 (en) * | 2012-09-07 | 2014-03-13 | Edison Pharmaceuticals, Inc. | Benzoquinone derivatives for treating oxidative stress disorders |
| NZ628963A (en) * | 2012-11-13 | 2017-02-24 | Gordagen Pharmaceuticals Pty Ltd | Transmucosal delivery of tocotrienol |
| US9868711B2 (en) | 2013-03-15 | 2018-01-16 | Bioelectron Technology Corporation | Phenazine-3-one and phenothiazine-3-one derivatives for treatment of oxidative stress disorders |
| US9670170B2 (en) | 2013-03-15 | 2017-06-06 | Bioelectron Technology Corporation | Resorufin derivatives for treatment of oxidative stress disorders |
| US9296712B2 (en) | 2013-03-15 | 2016-03-29 | Edison Pharmaceuticals, Inc. | Resorufin derivatives for treatment of oxidative stress disorders |
| EP2970158B1 (en) | 2013-03-15 | 2019-02-20 | BioElectron Technology Corporation | Alkyl-heteroaryl substituted quinone derivatives for treatment of oxidative stress disorders |
| RU2578451C1 (ru) * | 2014-12-09 | 2016-03-27 | Государственное Бюджетное Образовательное Учреждение Высшего Профессионального Образования "Амурская Государственная Медицинская Академия" Министерства Здравоохранения Российской Федерации | Способ повышения устойчивости головного мозга к ишемии во время реконструктивных операций на брахиоцефальных артериях |
| EP3233786B1 (en) | 2014-12-16 | 2022-03-16 | PTC Therapeutics, Inc. | Polymorphic and amorphous forms of (r)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide |
| EP3390377A1 (en) | 2015-12-16 | 2018-10-24 | BioElectron Technology Corporation | Improved methods for enriching alpha-tocotrienol from mixed tocol compositions |
| US10703701B2 (en) | 2015-12-17 | 2020-07-07 | Ptc Therapeutics, Inc. | Fluoroalkyl, fluoroalkoxy, phenoxy, heteroaryloxy, alkoxy, and amine 1,4-benzoquinone derivatives for treatment of oxidative stress disorders |
| CA3017485A1 (en) | 2016-03-16 | 2017-09-21 | Cidara Therapeutics, Inc. | Dosing regimens for treatment of fungal infections |
| US10707531B1 (en) | 2016-09-27 | 2020-07-07 | New Dominion Enterprises Inc. | All-inorganic solvents for electrolytes |
| JP2018083799A (ja) | 2016-11-15 | 2018-05-31 | バイオエレクトロン テクノロジー コーポレイション | ２−置換アミノ−ナフト［１，２−ｄ］イミダゾール−５−オン化合物またはその製薬学上許容される塩 |
| WO2019014333A1 (en) | 2017-07-12 | 2019-01-17 | Cidara Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR THE TREATMENT OF FUNGAL INFECTIONS |
| WO2020010180A1 (en) * | 2018-07-03 | 2020-01-09 | Cardio Vascular Bio Therapeutics, Inc. | Compositions and methods for treating stroke |
| KR102337954B1 (ko) * | 2018-08-16 | 2021-12-10 | 차의과학대학교 산학협력단 | 뇌졸중 치료용 조성물 및 이를 스크리닝하는 방법 |
| PL3866772T3 (pl) | 2018-10-17 | 2024-04-08 | Ptc Therapeutics, Inc. | 2,3,5-trimetylo-6-nonylocykloheksa-2,5-dieno-1,4-dion do hamowania i leczenia alfa-synukleinopatii, tauopatii i innych zaburzeń |
| KR20220078644A (ko) | 2019-10-04 | 2022-06-10 | 스텔스 바이오테라퓨틱스 인코포레이티드 | 미토콘드리아 질환 치료를 위한 바티퀴논의 퀴논-, 히드로퀴논- 및 나프토퀴논-유사체 |
| US20210162003A1 (en) * | 2019-10-17 | 2021-06-03 | The Penn State Research Foundation | Regenerating functional neurons for treatment of hemorrhagic stroke |
| JP2023520462A (ja) | 2020-04-03 | 2023-05-17 | ステルス バイオセラピューティクス インコーポレイテッド | フリードライヒ運動失調症を含むミトコンドリア病の予防および／または治療のための組成物および方法 |
| EP4268183B1 (en) * | 2020-12-22 | 2025-08-27 | Koninklijke Philips N.V. | Locating vascular constrictions |
| CN113066113B (zh) * | 2021-04-27 | 2022-01-11 | 河北医科大学第二医院 | 自发性高血压大鼠脑模板和地图集的构建方法及设备 |
| KR20240032997A (ko) | 2021-07-08 | 2024-03-12 | 피티씨 테라퓨틱스, 인크. | 2,3,5-트리메틸-6-노닐사이클로헥사-2,5-디엔-1,4-디온을 포함하는 약제학적 조성물 |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5938203B2 (ja) * | 1976-04-26 | 1984-09-14 | エーザイ株式会社 | 補酵素ｑを主成分とする脳循環障害治療剤 |
| US5872108A (en) | 1995-03-06 | 1999-02-16 | Interneuron Pharmaceuticals, Inc. | Reduction of infarct volume using citicoline |
| US6232060B1 (en) * | 1996-01-19 | 2001-05-15 | Galileo Laboratories, Inc. | Assay system for anti-stress agents |
| US5801159A (en) * | 1996-02-23 | 1998-09-01 | Galileo Laboratories, Inc. | Method and composition for inhibiting cellular irreversible changes due to stress |
| FR2753098B1 (fr) * | 1996-09-06 | 1998-11-27 | Sod Conseils Rech Applic | Composition pharmaceutique comprenant au moins un inhibiteur de no synthase et au moins un piegeur des formes reactives de l'oxygene |
| AU746369B2 (en) | 1997-11-17 | 2002-04-18 | Lipogenics, Inc. | Methods for preventing restenosis using tocotrienols |
| US6048891A (en) * | 1998-12-17 | 2000-04-11 | Loma Linda University Medical Center | Use of γ-tocopherol and its oxidative metabolite LLU-α in the treatment of natriuretic disease |
| WO2000078296A2 (en) | 1999-06-17 | 2000-12-28 | Basf Aktiengesellschaft | Tocotrienol and/or tocotrienol derivatives for the treatment or prophylaxis of glutamate- and/or calcium-induced disorders |
| US6426362B1 (en) * | 1999-10-08 | 2002-07-30 | Galileo Laboratories, Inc. | Formulations of tocopherols and methods of making and using them |
| US6528042B1 (en) * | 1999-10-08 | 2003-03-04 | Galileo Laboratories, Inc. | Compositions of flavonoids for use as cytoprotectants and methods of making and using them |
| US6346544B2 (en) * | 2000-03-02 | 2002-02-12 | Oklahoma Medical Research Foundation | Desmethyl tocopherols for protecting cardiovascular tissue |
| DE10034233A1 (de) * | 2000-07-14 | 2002-01-24 | Basf Ag | Tocotrienolchinon-Cyclisierungsprodukte |
| US7034054B2 (en) * | 2000-12-15 | 2006-04-25 | Galileo Pharmaceuticals, Inc. | Methods for the prevention and treatment of cerebral ischemia using non-alpha tocopherols |
| AU2002239748A1 (en) * | 2000-12-15 | 2002-06-24 | Galileo Laboratories, Inc. | Use of tocopherol, metabolites or derivatives thereof or flavonoid metabolites or derivatives thereof in the manufacture of a medicament for the treatment of tissue ischemia |
| US6608196B2 (en) * | 2001-05-03 | 2003-08-19 | Galileo Pharmaceuticals, Inc. | Process for solid supported synthesis of pyruvate-derived compounds |
| MXPA04001555A (es) * | 2001-08-21 | 2004-10-27 | Galileo Pharmaceuticals Inc | Composiciones enriquecidas con tocoferol y mejoramiento de sintomas inflamatorios. |
| WO2003043570A2 (en) * | 2001-11-15 | 2003-05-30 | Galileo Laboratories, Inc. | Formulations and methods for treatment or amelioration of inflammatory conditions |
| US20040152764A1 (en) * | 2001-12-14 | 2004-08-05 | Miller Guy M. | Compositions and methods for the prevention and treatment of cerebral ischemia |
| US6653346B1 (en) * | 2002-02-07 | 2003-11-25 | Galileo Pharmaceuticals, Inc. | Cytoprotective benzofuran derivatives |
| US7078541B2 (en) * | 2002-02-07 | 2006-07-18 | Galileo Pharmaceuticals, Inc. | Benzofuran derivatives |
| JP4599292B2 (ja) * | 2002-10-30 | 2010-12-15 | エジソン ファーマシューティカルズ， インコーポレイテッド | 物理的−化学的特性に基づく治療用化合物の同定 |
| CA2583087C (en) * | 2003-09-19 | 2012-07-10 | Galileo Pharmaceuticals, Inc. | Chroman derivatives |
| US7393662B2 (en) * | 2004-09-03 | 2008-07-01 | Centocor, Inc. | Human EPO mimetic hinge core mimetibodies, compositions, methods and uses |
| WO2006130775A2 (en) * | 2005-06-01 | 2006-12-07 | Edison Pharmaceuticals, Inc. | Redox-active therapeutics for treatment of mitochondrial diseases and other conditions and modulation of energy biomakers |
| PT1933821T (pt) * | 2005-09-15 | 2020-10-15 | Ptc Therapeutics Inc | Variantes de cauda de terapêuticos redox-ativos para tratamento de doenças mitocondriais e outras condições e modulação de biomarcadores energéticos |
| JP5374162B2 (ja) * | 2006-02-22 | 2013-12-25 | エジソン ファーマシューティカルズ， インコーポレイテッド | ミトコンドリア病および他の症状の処置のためのレドックス活性化治療の側鎖変異体およびエネルギーバイオマーカーの調節 |
| CA2674368A1 (en) * | 2007-01-10 | 2008-07-17 | Edison Pharmaceuticals, Inc. | Treatment of respiratory chain disorders using compounds having erythropoietin or thrombopoietin activity |
| EP3456707B1 (en) * | 2007-11-06 | 2020-04-15 | PTC Therapeutics, Inc. | 4- (p-quinonyl)-2-hydroxybutanamide derivatives for treatment of mitochondrial diseases |
| AU2008346956A1 (en) * | 2008-01-07 | 2009-07-16 | Centocor, Ortho Biotech Inc. | Method of treating erythropoietin hyporesponsive anemias |
| EA023618B1 (ru) * | 2008-01-08 | 2016-06-30 | Эдисон Фармасьютикалз, Инк. | Производные (гет)арил-п-хинона для лечения митохондриальных болезней |
| CA2717734A1 (en) * | 2008-03-05 | 2009-09-11 | Edison Pharmaceuticals, Inc | 2-substituted-p-quinone derivatives for treatment of oxidative stress diseases |
| WO2009111543A2 (en) * | 2008-03-05 | 2009-09-11 | Edison Pharmaceuticals, Inc. | Treatment of hearing and balance impairments with redox-active therapeutics |
| US20110142834A1 (en) * | 2008-05-15 | 2011-06-16 | Edison Pharmaceuticals, Inc. | Treatment of hearing and balance impairments using compounds having erythropoietin activity |
| EP2303309A2 (en) * | 2008-05-22 | 2011-04-06 | Edison Pharmaceuticals, Inc. | Treatment of mitochondrial diseases with an erythropoietin mimetic |
| WO2009158348A1 (en) * | 2008-06-25 | 2009-12-30 | Edison Pharmaceuticals, Inc. | 2-heterocyclylaminoalkyl-(p-quinone) derivatives for treatment of oxidative stress diseases |
| WO2010005989A1 (en) * | 2008-07-09 | 2010-01-14 | Edison Pharmaceuticals, Inc. | Dermatological compositions with anti-aging and skin even-toning properties |
| WO2010014361A1 (en) * | 2008-07-30 | 2010-02-04 | Edison Pharmaceuticals, Inc. | Naphthoquinone compositions with anti-aging, anti- inflammatory and skin even-toning properties |
| EP3827815B1 (en) * | 2008-09-10 | 2023-09-06 | PTC Therapeutics, Inc. | Treatment of pervasive developmental disorders with redox-active therapeutics |
| WO2010045220A1 (en) * | 2008-10-14 | 2010-04-22 | Edison Pharmaceuticals, Inc. | Treatment of oxidative stress disorders including contrast nephropathy, radiation damage and disruptions in the function of red cells |
| TR201819154T4 (tr) * | 2008-10-28 | 2019-01-21 | Bioelectron Tech Corp | Alfa-tokotrienol kuinone ve ara ürünlerini içeren bileşim. |
| WO2010126909A1 (en) * | 2009-04-28 | 2010-11-04 | Edison Pharmaceuticals, Inc. | Formulation of tocotrienol quinones for the treatment of ophthalmic diseases |
| BRPI1015006A2 (pt) * | 2009-04-28 | 2019-09-24 | Ampere Life Sciences Inc | uso tópico, periocular, ou intraocular de tocotrienóis para o tratamento de doenças oftálmicas |
| WO2010126911A1 (en) * | 2009-04-28 | 2010-11-04 | Edison Pharmaceuticals, Inc. | Treatment of leber's hereditary optic neuropathy and dominant optic atrophy with tocotrienol quinones |
| JP2012531411A (ja) * | 2009-06-25 | 2012-12-10 | アンペア ライフ サイエンシーズ，インコーポレイテッド | トコトリエノールまたはトコトリエノール濃縮抽出物を用いた広汎性発達障害の処置 |
| EP2519232A1 (en) * | 2009-12-31 | 2012-11-07 | Edison Pharmaceuticals, Inc. | Treatment of leigh syndrome and leigh-like syndrome with tocotrienol quinones |
| JP2013523816A (ja) * | 2010-04-06 | 2013-06-17 | エジソン ファーマシューティカルズ， インコーポレイテッド | 毛細血管拡張性運動失調症の治療 |
| AU2011245384C1 (en) * | 2010-04-27 | 2016-09-01 | Bioelectron Technology Corporation | Formulations of quinones for the treatment of ophthalmic diseases |
| US20120101169A1 (en) * | 2010-07-14 | 2012-04-26 | Penwest Pharmaceuticals Co. | Methods of providing anticoagulation effects in subjects |
| US20120295985A1 (en) * | 2010-11-19 | 2012-11-22 | Miller Guy M | Methods for improving blood glucose control |
-
2010
- 2010-08-24 CA CA2772294A patent/CA2772294C/en active Active
- 2010-08-24 PT PT107477770T patent/PT2470168T/pt unknown
- 2010-08-24 JP JP2012526918A patent/JP5785546B2/ja not_active Expired - Fee Related
- 2010-08-24 EP EP10747777.0A patent/EP2470168B1/en active Active
- 2010-08-24 AU AU2010286704A patent/AU2010286704B2/en not_active Ceased
- 2010-08-24 PL PL10747777T patent/PL2470168T3/pl unknown
- 2010-08-24 HU HUE10747777A patent/HUE037592T2/hu unknown
- 2010-08-24 EA EA201200355A patent/EA028677B1/ru not_active IP Right Cessation
- 2010-08-24 BR BR112012004167A patent/BR112012004167A2/pt not_active Application Discontinuation
- 2010-08-24 MX MX2012002374A patent/MX337990B/es active IP Right Grant
- 2010-08-24 NO NO10747777A patent/NO2470168T3/no unknown
- 2010-08-24 WO PCT/US2010/046503 patent/WO2011025785A1/en not_active Ceased
- 2010-08-24 SI SI201031644T patent/SI2470168T1/en unknown
- 2010-08-24 US US12/862,705 patent/US20110207828A1/en not_active Abandoned
- 2010-08-24 ES ES10747777.0T patent/ES2663709T3/es active Active
- 2010-08-24 CN CN201080048363.2A patent/CN102647981B/zh not_active Expired - Fee Related
- 2010-08-24 DK DK10747777.0T patent/DK2470168T3/en active
-
2015
- 2015-02-16 JP JP2015027506A patent/JP2015091899A/ja active Pending
-
2016
- 2016-02-10 US US15/040,961 patent/US20170007553A1/en not_active Abandoned
-
2018
- 2018-08-09 US US16/100,062 patent/US20180344667A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EA201200355A1 (ru) | 2012-07-30 |
| US20180344667A1 (en) | 2018-12-06 |
| EA028677B1 (ru) | 2017-12-29 |
| PT2470168T (pt) | 2018-03-28 |
| EP2470168A1 (en) | 2012-07-04 |
| HUE037592T2 (hu) | 2018-09-28 |
| BR112012004167A2 (pt) | 2016-03-29 |
| NO2470168T3 (enExample) | 2018-06-30 |
| MX337990B (es) | 2016-03-30 |
| JP2013503168A (ja) | 2013-01-31 |
| SI2470168T1 (en) | 2018-05-31 |
| JP2015091899A (ja) | 2015-05-14 |
| MX2012002374A (es) | 2012-04-10 |
| EP2470168B1 (en) | 2018-01-31 |
| PL2470168T3 (pl) | 2018-06-29 |
| AU2010286704A1 (en) | 2012-03-22 |
| DK2470168T3 (en) | 2018-05-07 |
| CN102647981B (zh) | 2016-09-28 |
| CN102647981A (zh) | 2012-08-22 |
| CA2772294C (en) | 2018-08-21 |
| US20110207828A1 (en) | 2011-08-25 |
| WO2011025785A1 (en) | 2011-03-03 |
| ES2663709T3 (es) | 2018-04-16 |
| CA2772294A1 (en) | 2011-03-03 |
| US20170007553A1 (en) | 2017-01-12 |
| AU2010286704B2 (en) | 2016-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5785546B2 (ja) | 脳虚血を予防または処置する方法 | |
| US7034054B2 (en) | Methods for the prevention and treatment of cerebral ischemia using non-alpha tocopherols | |
| RU2528097C2 (ru) | Способы и составы для лечения субарахноидального кровоизлияния коронарной и артериальной аневризмы | |
| US20100197610A1 (en) | Fructose 1, 6 bisphosphate - a novel anticonvulsant drug | |
| CN105943530B (zh) | 铁死亡抑制剂在制备治疗铁过载疾病的药物中的应用 | |
| CN102526006B (zh) | 单羧酸和二羧酸的酰胺化物在肾病治疗中的应用 | |
| WO2021118359A1 (en) | Compounds for treatment of alzheimer's disease | |
| WO2011157059A1 (zh) | 异类叶升麻苷或其药学上可接受的盐的用途 | |
| CN115315197A (zh) | 细胞衰老抑制用组合物及抑制细胞衰老的方法 | |
| US9029419B2 (en) | Use of zinc N-acetyltaurinate | |
| HK1171665A (en) | Methods for the prevention and treatment of cerebral ischemia | |
| HK1171665B (en) | Methods for the prevention and treatment of cerebral ischemia | |
| CN116801866A (zh) | α-细辛脑在制备预防或治疗出血性脑卒中药物中的应用 | |
| Sun et al. | Kudiezi Injection Attenuates Apoptosis and Neuroinflammation for Ameliorating Angiogenesis via miR-21/PDCD4/NF-κB Axis in MCAO/Reperfusion Rats | |
| EP4338798A1 (en) | Pharmaceutical preparation containing genistein for use in the prevention or treatment of glaucoma and/or ocular hypertension | |
| EP1977748B1 (en) | Compounds having neuroprotective properties | |
| KR20080094466A (ko) | 대사증후군 치료용 약제 조성물 | |
| CN115581702A (zh) | 芍药素-3-o-阿拉伯糖苷在制备药物或保健食品的应用 | |
| CN115645430A (zh) | 飞燕草素-3-o-半乳糖苷在制备药物或保健食品的应用 | |
| JP2002121132A (ja) | 発がん抑制剤および発がん抑制方法 | |
| KR20130091604A (ko) | 시난디온 ａ를 포함하는 항염증용 조성물 | |
| CN112587512A (zh) | 一种治疗脑卒中的asbdv药物组合物及其制剂与应用 | |
| KR20200126354A (ko) | 진세노사이드 Rb2를 포함하는 신경세포 보호용 조성물 | |
| CN112516119A (zh) | 一种治疗脑卒中的asbd药物组合物及其制剂与应用 | |
| OA21243A (en) | Compounds for treatment of alzheimer's disease. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130823 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130823 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140814 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20141113 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20141120 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150216 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150624 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150724 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5785546 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |