AU2015282424A1 - Succinate dehydrogenase inhibitors (SDHi's) - Google Patents

Info

Publication number

AU2015282424A1

AU2015282424A1 AU2015282424A AU2015282424A AU2015282424A1 AU 2015282424 A1 AU2015282424 A1 AU 2015282424A1 AU 2015282424 A AU2015282424 A AU 2015282424A AU 2015282424 A AU2015282424 A AU 2015282424A AU 2015282424 A1 AU2015282424 A1 AU 2015282424A1

Authority

AU

Australia

Prior art keywords

succinate

pharmaceutically acceptable

acceptable salt

reperfusion

prodrug

Prior art date

2014-07-03

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• Discuss

• 102000019259 Succinate Dehydrogenase Human genes 0.000 title claims abstract description 64
• 108010012901 Succinate Dehydrogenase Proteins 0.000 title claims abstract description 64
• 239000003112 inhibitor Substances 0.000 title claims abstract description 30
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims abstract description 132
• 150000003839 salts Chemical class 0.000 claims abstract description 97
• 239000000651 prodrug Substances 0.000 claims abstract description 71
• 229940002612 prodrug Drugs 0.000 claims abstract description 71
• 238000009825 accumulation Methods 0.000 claims abstract description 42
• 206010063837 Reperfusion injury Diseases 0.000 claims abstract description 36
• 229940124186 Dehydrogenase inhibitor Drugs 0.000 claims abstract description 23
• 238000011282 treatment Methods 0.000 claims abstract description 23
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 15
• 230000002265 prevention Effects 0.000 claims abstract description 14
• 239000013037 reversible inhibitor Substances 0.000 claims abstract description 11
• 208000028867 ischemia Diseases 0.000 claims description 98
• 230000010410 reperfusion Effects 0.000 claims description 86
• 238000004519 manufacturing process Methods 0.000 claims description 40
• BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical group COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 claims description 32
• 208000014674 injury Diseases 0.000 claims description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
• 238000000034 method Methods 0.000 claims description 17
• 208000006011 Stroke Diseases 0.000 claims description 16
• 230000002441 reversible effect Effects 0.000 claims description 16
• 238000001356 surgical procedure Methods 0.000 claims description 15
• 210000000056 organ Anatomy 0.000 claims description 12
• 208000035475 disorder Diseases 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 208000010125 myocardial infarction Diseases 0.000 claims description 7
• 230000017531 blood circulation Effects 0.000 claims description 6
• 238000002054 transplantation Methods 0.000 claims description 5
• 206010048962 Brain oedema Diseases 0.000 claims description 4
• 206010020772 Hypertension Diseases 0.000 claims description 4
• 206010028980 Neoplasm Diseases 0.000 claims description 4
• 208000006752 brain edema Diseases 0.000 claims description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 3
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
• 208000025962 Crush injury Diseases 0.000 claims description 3
• 208000010496 Heart Arrest Diseases 0.000 claims description 3
• 208000018262 Peripheral vascular disease Diseases 0.000 claims description 3
• 208000011191 Pulmonary vascular disease Diseases 0.000 claims description 3
• 208000014139 Retinal vascular disease Diseases 0.000 claims description 3
• 208000002223 abdominal aortic aneurysm Diseases 0.000 claims description 3
• 229940127090 anticoagulant agent Drugs 0.000 claims description 3
• 208000007474 aortic aneurysm Diseases 0.000 claims description 3
• 238000007675 cardiac surgery Methods 0.000 claims description 3
• 208000026106 cerebrovascular disease Diseases 0.000 claims description 3
• 239000003795 chemical substances by application Substances 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 230000008733 trauma Effects 0.000 claims description 3
• 200000000007 Arterial disease Diseases 0.000 claims description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
• 208000019695 Migraine disease Diseases 0.000 claims description 2
• 208000028922 artery disease Diseases 0.000 claims description 2
• 201000011510 cancer Diseases 0.000 claims description 2
• 238000007887 coronary angioplasty Methods 0.000 claims description 2
• 208000029078 coronary artery disease Diseases 0.000 claims description 2
• 230000009089 cytolysis Effects 0.000 claims description 2
• 206010012601 diabetes mellitus Diseases 0.000 claims description 2
• 238000002283 elective surgery Methods 0.000 claims description 2
• 206010027599 migraine Diseases 0.000 claims description 2
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims 2
• 101710088194 Dehydrogenase Proteins 0.000 claims 2
• SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
• 208000012947 ischemia reperfusion injury Diseases 0.000 abstract description 3
• 230000000302 ischemic effect Effects 0.000 description 63
• 210000002216 heart Anatomy 0.000 description 56
• 239000002207 metabolite Substances 0.000 description 50
• 210000001519 tissue Anatomy 0.000 description 48
• 239000003642 reactive oxygen metabolite Substances 0.000 description 45
• 238000001727 in vivo Methods 0.000 description 40
• 230000002438 mitochondrial effect Effects 0.000 description 40
• 230000035508 accumulation Effects 0.000 description 38
• 150000001875 compounds Chemical class 0.000 description 37
• 210000004027 cell Anatomy 0.000 description 33
• -1 compound 3-nitropropionate Chemical class 0.000 description 30
• 230000004102 tricarboxylic acid cycle Effects 0.000 description 29
• 239000000872 buffer Substances 0.000 description 26
• 230000006378 damage Effects 0.000 description 26
• 208000027418 Wounds and injury Diseases 0.000 description 24
• 230000002503 metabolic effect Effects 0.000 description 24
• 230000004907 flux Effects 0.000 description 23
• 241000700159 Rattus Species 0.000 description 20
• 230000000694 effects Effects 0.000 description 20
• MUXOBHXGJLMRAB-UHFFFAOYSA-N Dimethyl succinate Chemical compound COC(=O)CCC(=O)OC MUXOBHXGJLMRAB-UHFFFAOYSA-N 0.000 description 19
• 238000004458 analytical method Methods 0.000 description 19
• 238000006243 chemical reaction Methods 0.000 description 19
• 241000699666 Mus <mouse, genus> Species 0.000 description 18
• 241000699670 Mus sp. Species 0.000 description 18
• 230000005764 inhibitory process Effects 0.000 description 18
• 238000007254 oxidation reaction Methods 0.000 description 18
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 18
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 17
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 17
• 210000004413 cardiac myocyte Anatomy 0.000 description 17
• 230000003647 oxidation Effects 0.000 description 17
• XYJODUBPWNZLML-UHFFFAOYSA-N 5-ethyl-6-phenyl-6h-phenanthridine-3,8-diamine Chemical compound C12=CC(N)=CC=C2C2=CC=C(N)C=C2N(CC)C1C1=CC=CC=C1 XYJODUBPWNZLML-UHFFFAOYSA-N 0.000 description 16
• 210000004556 brain Anatomy 0.000 description 16
• 210000004165 myocardium Anatomy 0.000 description 16
• 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 15
• 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 15
• 238000002474 experimental method Methods 0.000 description 15
• 238000002705 metabolomic analysis Methods 0.000 description 15
• 239000008103 glucose Substances 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
• 230000004060 metabolic process Effects 0.000 description 13
• 239000012453 solvate Substances 0.000 description 13
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
• 229940009098 aspartate Drugs 0.000 description 12
• 230000001419 dependent effect Effects 0.000 description 12
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 12
• 230000037361 pathway Effects 0.000 description 12
• 230000010412 perfusion Effects 0.000 description 12
• 230000005565 malate-aspartate shuttle Effects 0.000 description 11
• 230000007246 mechanism Effects 0.000 description 11
• 206010021143 Hypoxia Diseases 0.000 description 10
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 10
• 230000001965 increasing effect Effects 0.000 description 10
• 238000001802 infusion Methods 0.000 description 10
• 238000002360 preparation method Methods 0.000 description 10
• 230000002829 reductive effect Effects 0.000 description 10
• 239000002904 solvent Substances 0.000 description 10
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• 206010061216 Infarction Diseases 0.000 description 9
• 230000007574 infarction Effects 0.000 description 9
• 210000003734 kidney Anatomy 0.000 description 9
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
• 230000001431 metabolomic effect Effects 0.000 description 9
• 210000001700 mitochondrial membrane Anatomy 0.000 description 9
• 229940052665 nadh Drugs 0.000 description 9
• BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 9
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 9
• 239000002213 purine nucleotide Substances 0.000 description 9
• 150000003212 purines Chemical class 0.000 description 9
• 230000009467 reduction Effects 0.000 description 9
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 8
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 8
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 238000007792 addition Methods 0.000 description 8
• 238000013459 approach Methods 0.000 description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
• 230000000747 cardiac effect Effects 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 210000004185 liver Anatomy 0.000 description 8
• 239000001301 oxygen Substances 0.000 description 8
• 229910052760 oxygen Inorganic materials 0.000 description 8
• 125000006239 protecting group Chemical group 0.000 description 8
• 230000029058 respiratory gaseous exchange Effects 0.000 description 8
• 239000011780 sodium chloride Substances 0.000 description 8
• OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 7
• 239000002585 base Substances 0.000 description 7
• 230000003247 decreasing effect Effects 0.000 description 7
• 201000010099 disease Diseases 0.000 description 7
• 239000003937 drug carrier Substances 0.000 description 7
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 7
• 238000011065 in-situ storage Methods 0.000 description 7
• 230000000155 isotopic effect Effects 0.000 description 7
• 210000003470 mitochondria Anatomy 0.000 description 7
• 239000000203 mixture Substances 0.000 description 7
• 210000003098 myoblast Anatomy 0.000 description 7
• 229910052757 nitrogen Inorganic materials 0.000 description 7
• NQRKYASMKDDGHT-UHFFFAOYSA-M (aminooxy)acetate Chemical compound NOCC([O-])=O NQRKYASMKDDGHT-UHFFFAOYSA-M 0.000 description 6
• 108091006146 Channels Proteins 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
• 230000005961 cardioprotection Effects 0.000 description 6
• 230000006870 function Effects 0.000 description 6
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 6
• 210000004962 mammalian cell Anatomy 0.000 description 6
• 210000004379 membrane Anatomy 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• 230000037353 metabolic pathway Effects 0.000 description 6
• 230000002107 myocardial effect Effects 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 239000000243 solution Substances 0.000 description 6
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
• 125000000217 alkyl group Chemical group 0.000 description 5
• 230000027455 binding Effects 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 229940088598 enzyme Drugs 0.000 description 5
• 125000000524 functional group Chemical group 0.000 description 5
• 230000007954 hypoxia Effects 0.000 description 5
• 238000003384 imaging method Methods 0.000 description 5
• 238000001990 intravenous administration Methods 0.000 description 5
• 238000002372 labelling Methods 0.000 description 5
• 238000005259 measurement Methods 0.000 description 5
• 230000007959 normoxia Effects 0.000 description 5
• 239000002243 precursor Substances 0.000 description 5
• 230000004224 protection Effects 0.000 description 5
• 230000001681 protective effect Effects 0.000 description 5
• 230000001172 regenerating effect Effects 0.000 description 5
• 238000001228 spectrum Methods 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• 230000001052 transient effect Effects 0.000 description 5
• 230000002407 ATP formation Effects 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
• 241001529936 Murinae Species 0.000 description 4
• QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 4
• 230000004913 activation Effects 0.000 description 4
• 238000001994 activation Methods 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 230000001086 cytosolic effect Effects 0.000 description 4
• 230000035487 diastolic blood pressure Effects 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 238000009826 distribution Methods 0.000 description 4
• 238000007710 freezing Methods 0.000 description 4
• 150000004677 hydrates Chemical class 0.000 description 4
• 230000001146 hypoxic effect Effects 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 230000000926 neurological effect Effects 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 4
• 230000004044 response Effects 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• 230000032258 transport Effects 0.000 description 4
• 229940075420 xanthine Drugs 0.000 description 4
• MNULEGDCPYONBU-WMBHJXFZSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-WMBHJXFZSA-N 0.000 description 3
• MNULEGDCPYONBU-DJRUDOHVSA-N (1s,4r,5z,5'r,6'r,7e,10s,11r,12s,14r,15s,18r,19r,20s,21e,26r,27s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@H]1CC[C@H](\C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)C(C)C(=O)[C@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)OC([C@H]2C)C1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 MNULEGDCPYONBU-DJRUDOHVSA-N 0.000 description 3
• MNULEGDCPYONBU-YNZHUHFTSA-N (4Z,18Z,20Z)-22-ethyl-7,11,14,15-tetrahydroxy-6'-(2-hydroxypropyl)-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC1C(C2C)OC(=O)\C=C/C(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)C\C=C/C=C\C(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-YNZHUHFTSA-N 0.000 description 3
• MNULEGDCPYONBU-VVXVDZGXSA-N (5e,5'r,7e,10s,11r,12s,14s,15r,16r,18r,19s,20r,21e,26r,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)OC([C@H]1C)[C@H]2C)\C=C\C=C\C(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-VVXVDZGXSA-N 0.000 description 3
• PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 3
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
• WBLZUCOIBUDNBV-UHFFFAOYSA-N 3-nitropropanoic acid Chemical compound OC(=O)CC[N+]([O-])=O WBLZUCOIBUDNBV-UHFFFAOYSA-N 0.000 description 3
• MNULEGDCPYONBU-UHFFFAOYSA-N 4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)CC=CC=CC(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-UHFFFAOYSA-N 0.000 description 3
• 102000055161 Adenylosuccinate lyases Human genes 0.000 description 3
• 206010002091 Anaesthesia Diseases 0.000 description 3
• 241000995051 Brenda Species 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 206010008089 Cerebral artery occlusion Diseases 0.000 description 3
• 102000029816 Collagenase Human genes 0.000 description 3
• 108060005980 Collagenase Proteins 0.000 description 3
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
• 101001131930 Homo sapiens Transcriptional activator protein Pur-beta Proteins 0.000 description 3
• UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 3
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 3
• 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 3
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
• 239000004472 Lysine Substances 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 238000001949 anaesthesia Methods 0.000 description 3
• 230000037005 anaesthesia Effects 0.000 description 3
• 239000003963 antioxidant agent Substances 0.000 description 3
• 235000006708 antioxidants Nutrition 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 230000000903 blocking effect Effects 0.000 description 3
• 208000029028 brain injury Diseases 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• 230000003293 cardioprotective effect Effects 0.000 description 3
• 150000001768 cations Chemical class 0.000 description 3
• 229960002424 collagenase Drugs 0.000 description 3
• 230000000052 comparative effect Effects 0.000 description 3
• 230000009137 competitive binding Effects 0.000 description 3
• 210000004351 coronary vessel Anatomy 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 239000008121 dextrose Substances 0.000 description 3
• 230000008014 freezing Effects 0.000 description 3
• 210000005003 heart tissue Anatomy 0.000 description 3
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000010253 intravenous injection Methods 0.000 description 3
• 230000002427 irreversible effect Effects 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 229940001447 lactate Drugs 0.000 description 3
• 230000036722 left ventricular developed pressure Effects 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 229910021645 metal ion Inorganic materials 0.000 description 3
• 201000007309 middle cerebral artery infarction Diseases 0.000 description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 229930191479 oligomycin Natural products 0.000 description 3
• MNULEGDCPYONBU-AWJDAWNUSA-N oligomycin A Polymers O([C@H]1CC[C@H](/C=C/C=C/C[C@@H](C)[C@H](O)[C@@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)O[C@@H]([C@@H]2C)[C@@H]1C)CC)[C@@]12CC[C@H](C)[C@H](C[C@@H](C)O)O1 MNULEGDCPYONBU-AWJDAWNUSA-N 0.000 description 3
• 229960001412 pentobarbital Drugs 0.000 description 3
• 230000035699 permeability Effects 0.000 description 3
• 229940076788 pyruvate Drugs 0.000 description 3
• 238000010791 quenching Methods 0.000 description 3
• 230000035806 respiratory chain Effects 0.000 description 3
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 238000004088 simulation Methods 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 238000010186 staining Methods 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 210000000130 stem cell Anatomy 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• TXBBUSUXYMIVOS-UHFFFAOYSA-N thenoyltrifluoroacetone Chemical compound FC(F)(F)C(=O)CC(=O)C1=CC=CS1 TXBBUSUXYMIVOS-UHFFFAOYSA-N 0.000 description 3
• 229940040064 ubiquinol Drugs 0.000 description 3
• QNTNKSLOFHEFPK-UPTCCGCDSA-N ubiquinol-10 Chemical compound COC1=C(O)C(C)=C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)C(O)=C1OC QNTNKSLOFHEFPK-UPTCCGCDSA-N 0.000 description 3
• PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 description 3
• 229960005318 vigabatrin Drugs 0.000 description 3
• OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
• AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-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
• KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 2
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 239000004475 Arginine Substances 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
• 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-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
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 2
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
• 241000283086 Equidae Species 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 239000004471 Glycine Substances 0.000 description 2
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
• CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 206010063897 Renal ischaemia Diseases 0.000 description 2
• 241000270295 Serpentes Species 0.000 description 2
• 108010023197 Streptokinase Proteins 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 150000001409 amidines Chemical class 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 125000000129 anionic group Chemical group 0.000 description 2
• 230000003078 antioxidant effect Effects 0.000 description 2
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
• 229960005261 aspartic acid Drugs 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
• 239000006227 byproduct Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 125000002091 cationic group Chemical group 0.000 description 2
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
• 229960001231 choline Drugs 0.000 description 2
• ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 2
• 235000017471 coenzyme Q10 Nutrition 0.000 description 2
• 238000010835 comparative analysis Methods 0.000 description 2
• 238000004624 confocal microscopy Methods 0.000 description 2
• CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
• 210000000172 cytosol Anatomy 0.000 description 2
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• 230000003292 diminished effect Effects 0.000 description 2
• 230000009189 diving Effects 0.000 description 2
• 229940088679 drug related substance Drugs 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 125000002587 enol group Chemical group 0.000 description 2
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
• 238000011067 equilibration Methods 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 229930195712 glutamate Natural products 0.000 description 2
• 230000034659 glycolysis Effects 0.000 description 2
• 229920000669 heparin Polymers 0.000 description 2
• 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 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 230000001631 hypertensive effect Effects 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 238000001361 intraarterial 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
• 229960002725 isoflurane Drugs 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 238000001948 isotopic labelling Methods 0.000 description 2
• 239000003446 ligand Substances 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
• 229940049920 malate Drugs 0.000 description 2
• BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 2
• 150000002690 malonic acid derivatives Chemical class 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• 150000004702 methyl esters Chemical class 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 208000031225 myocardial ischemia Diseases 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 230000007658 neurological function Effects 0.000 description 2
• BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
• 150000007523 nucleic acids Chemical class 0.000 description 2
• 102000039446 nucleic acids Human genes 0.000 description 2
• 108020004707 nucleic acids Proteins 0.000 description 2
• 239000000162 organ preservation solution Substances 0.000 description 2
• 150000002891 organic anions Chemical class 0.000 description 2
• 150000002894 organic compounds Chemical class 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 230000007170 pathology Effects 0.000 description 2
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 239000008194 pharmaceutical composition Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 230000005588 protonation Effects 0.000 description 2
• 238000011002 quantification Methods 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 238000002271 resection Methods 0.000 description 2
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
• 230000003595 spectral effect Effects 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 229960005202 streptokinase Drugs 0.000 description 2
• 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 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 2
• 230000007704 transition Effects 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 1
• PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-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
• TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
• YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-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
• KPGXRSRHYNQIFN-UHFFFAOYSA-L 2-oxoglutarate(2-) Chemical compound [O-]C(=O)CCC(=O)C([O-])=O KPGXRSRHYNQIFN-UHFFFAOYSA-L 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
• 108010060511 4-Aminobutyrate Transaminase Proteins 0.000 description 1
• 102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 108700037034 Adenylosuccinate lyase deficiency Proteins 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
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• RZZPDXZPRHQOCG-OJAKKHQRSA-N CDP-choline Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-N 0.000 description 1
• 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• BMZRVOVNUMQTIN-UHFFFAOYSA-N Carbonyl Cyanide para-Trifluoromethoxyphenylhydrazone Chemical compound FC(F)(F)OC1=CC=C(NN=C(C#N)C#N)C=C1 BMZRVOVNUMQTIN-UHFFFAOYSA-N 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 206010008088 Cerebral artery embolism Diseases 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• 241000282994 Cervidae Species 0.000 description 1
• 241001432959 Chernes Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
• UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 1
• 102000004654 Cyclic GMP-Dependent Protein Kinases Human genes 0.000 description 1
• 108010003591 Cyclic GMP-Dependent Protein Kinases Proteins 0.000 description 1
• DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 206010013647 Drowning Diseases 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 102000015782 Electron Transport Complex III Human genes 0.000 description 1
• 108010024882 Electron Transport Complex III Proteins 0.000 description 1
• 239000001263 FEMA 3042 Substances 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 108010010803 Gelatin Proteins 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
• 239000007995 HEPES buffer Substances 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• 241001559542 Hippocampus hippocampus Species 0.000 description 1
• 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 206010058558 Hypoperfusion Diseases 0.000 description 1
• 208000001953 Hypotension Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 102000016924 KATP Channels Human genes 0.000 description 1
• 108010053914 KATP Channels Proteins 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 208000007201 Myocardial reperfusion injury Diseases 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
• 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• 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 1
• LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 229920000037 Polyproline Polymers 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
• 239000004792 Prolene Substances 0.000 description 1
• 108010053763 Pyruvate Carboxylase Proteins 0.000 description 1
• 102100039895 Pyruvate carboxylase, mitochondrial Human genes 0.000 description 1
• AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
• 239000008156 Ringer's lactate solution Substances 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 101710145796 Staphylokinase Proteins 0.000 description 1
• 102100037464 Succinate receptor 1 Human genes 0.000 description 1
• 101710197531 Succinate receptor 1 Proteins 0.000 description 1
• 229930006000 Sucrose Natural products 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
• 241000282887 Suidae Species 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
• 229920002253 Tannate Polymers 0.000 description 1
• 108010039185 Tenecteplase Proteins 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 238000002679 ablation Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 208000000391 adenylosuccinate lyase deficiency Diseases 0.000 description 1
• OFBHPPMPBOJXRT-VWJPMABRSA-N adenylosuccinic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C2=NC=NC(N[C@@H](CC(O)=O)C(O)=O)=C2N=C1 OFBHPPMPBOJXRT-VWJPMABRSA-N 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 150000001299 aldehydes Chemical class 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
• 239000003513 alkali Substances 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 1
• 229960003459 allopurinol Drugs 0.000 description 1
• PMMURAAUARKVCB-UHFFFAOYSA-N alpha-D-ara-dHexp Natural products OCC1OC(O)CC(O)C1O PMMURAAUARKVCB-UHFFFAOYSA-N 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 239000001099 ammonium carbonate Substances 0.000 description 1
• 235000012501 ammonium carbonate Nutrition 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 150000001449 anionic compounds Chemical class 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 210000000709 aorta Anatomy 0.000 description 1
• 229960003886 apixaban Drugs 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 238000003491 array Methods 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 238000004555 blood preservation Methods 0.000 description 1
• 230000036770 blood supply Effects 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 230000006931 brain damage Effects 0.000 description 1
• 231100000874 brain damage Toxicity 0.000 description 1
• 201000008247 brain infarction Diseases 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 229960003563 calcium carbonate Drugs 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 235000011148 calcium chloride Nutrition 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
• 235000020827 calorie restriction Nutrition 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 229960004203 carnitine Drugs 0.000 description 1
• 210000001168 carotid artery common Anatomy 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 150000001767 cationic compounds Chemical class 0.000 description 1
• 230000019522 cellular metabolic process Effects 0.000 description 1
• 230000006706 cellular oxygen consumption Effects 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000007806 chemical reaction intermediate Substances 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 230000035606 childbirth Effects 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000012505 colouration Methods 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 229960003624 creatine Drugs 0.000 description 1
• 239000006046 creatine Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 229940109275 cyclamate Drugs 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 229960003850 dabigatran Drugs 0.000 description 1
• YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 description 1
• 230000006196 deacetylation Effects 0.000 description 1
• 238000003381 deacetylation reaction Methods 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 230000027721 electron transport chain Effects 0.000 description 1
• 230000003028 elevating effect Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 150000002081 enamines Chemical class 0.000 description 1
• 150000002085 enols Chemical class 0.000 description 1
• 229960000610 enoxaparin Drugs 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 229940031098 ethanolamine Drugs 0.000 description 1
• 125000004494 ethyl ester group Chemical group 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
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 230000001747 exhibiting effect Effects 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
• 239000003527 fibrinolytic agent Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 description 1
• 229960001318 fondaparinux Drugs 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 230000002431 foraging effect Effects 0.000 description 1
• 229940044170 formate Drugs 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 239000000446 fuel Substances 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229960001731 gluceptate Drugs 0.000 description 1
• KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 229940097042 glucuronate Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 230000005484 gravity Effects 0.000 description 1
• 235000000334 grey box Nutrition 0.000 description 1
• 244000085685 grey box Species 0.000 description 1
• 230000004217 heart function Effects 0.000 description 1
• 210000004536 heart mitochondria Anatomy 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 229950000177 hibenzate Drugs 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 230000036543 hypotension Effects 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 230000015788 innate immune response Effects 0.000 description 1
• 229910001412 inorganic anion Inorganic materials 0.000 description 1
• 229910001411 inorganic cation Inorganic materials 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 230000007154 intracellular accumulation Effects 0.000 description 1
• 201000010849 intracranial embolism Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 230000003447 ipsilateral effect Effects 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 230000002530 ischemic preconditioning effect Effects 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 150000003951 lactams Chemical group 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229950010645 lanoteplase Drugs 0.000 description 1
• 108010051044 lanoteplase Proteins 0.000 description 1
• 238000002350 laparotomy Methods 0.000 description 1
• 210000005240 left ventricle Anatomy 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 210000005228 liver tissue Anatomy 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• 239000012160 loading buffer Substances 0.000 description 1
• 231100000053 low toxicity Toxicity 0.000 description 1
• 229940127215 low-molecular weight heparin Drugs 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 230000007102 metabolic function Effects 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 230000027829 mitochondrial depolarization Effects 0.000 description 1
• 230000004898 mitochondrial function Effects 0.000 description 1
• 230000006677 mitochondrial metabolism Effects 0.000 description 1
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 210000002464 muscle smooth vascular Anatomy 0.000 description 1
• GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 1
• 229940094933 n-dodecane Drugs 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000005487 naphthalate group Chemical group 0.000 description 1
• 210000004179 neuropil Anatomy 0.000 description 1
• 230000004112 neuroprotection Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• YKPWBJLKHZNNBR-UHFFFAOYSA-N nitro propanoate Chemical compound CCC(=O)O[N+]([O-])=O YKPWBJLKHZNNBR-UHFFFAOYSA-N 0.000 description 1
• 238000007034 nitrosation reaction Methods 0.000 description 1
• 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
• 231100000957 no side effect Toxicity 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 239000000346 nonvolatile oil Substances 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 229950004864 olamine Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\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
• 230000003287 optical effect Effects 0.000 description 1
• 239000000082 organ preservation Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002892 organic cations Chemical class 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• PXQPEWDEAKTCGB-UHFFFAOYSA-M orotate Chemical compound [O-]C(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-M 0.000 description 1
• 238000012261 overproduction Methods 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• 230000036284 oxygen consumption Effects 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 210000003540 papillary muscle Anatomy 0.000 description 1
• RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000001991 pathophysiological effect Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000003516 pericardium Anatomy 0.000 description 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 238000007747 plating Methods 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 229920001987 poloxamine Polymers 0.000 description 1
• 108010026466 polyproline Proteins 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 230000010411 postconditioning Effects 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000003761 preservation solution Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000037452 priming Effects 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 238000005086 pumping Methods 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 239000002212 purine nucleoside Substances 0.000 description 1
• 230000002488 pyknotic effect Effects 0.000 description 1
• 229940043131 pyroglutamate Drugs 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 229940100618 rectal suppository Drugs 0.000 description 1
• 239000006215 rectal suppository Substances 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 210000002796 renal vein Anatomy 0.000 description 1
• 230000027756 respiratory electron transport chain Effects 0.000 description 1
• 229960002917 reteplase Drugs 0.000 description 1
• 108010051412 reteplase Proteins 0.000 description 1
• 230000006965 reversible inhibition Effects 0.000 description 1
• 229960001148 rivaroxaban Drugs 0.000 description 1
• KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 229960001790 sodium citrate Drugs 0.000 description 1
• 235000011083 sodium citrates Nutrition 0.000 description 1
• 239000001540 sodium lactate Substances 0.000 description 1
• 229940005581 sodium lactate Drugs 0.000 description 1
• 235000011088 sodium lactate Nutrition 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 229940054269 sodium pyruvate Drugs 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 238000011630 spontaneously hypertensive stroke prone rat Methods 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 229940086735 succinate Drugs 0.000 description 1
• 150000003900 succinic acid esters Chemical class 0.000 description 1
• UIUJIQZEACWQSV-UHFFFAOYSA-N succinic semialdehyde Chemical compound OC(=O)CCC=O UIUJIQZEACWQSV-UHFFFAOYSA-N 0.000 description 1
• 108010013480 succinylated gelatin Proteins 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 210000000225 synapse Anatomy 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 230000009885 systemic effect Effects 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
• LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
• 229920002258 tannic acid Polymers 0.000 description 1
• 235000015523 tannic acid Nutrition 0.000 description 1
• 229940033123 tannic acid Drugs 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 229960003080 taurine Drugs 0.000 description 1
• 229960000216 tenecteplase Drugs 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• ICRHORQIUXBEPA-UHFFFAOYSA-N thionitrous acid Chemical compound SN=O ICRHORQIUXBEPA-UHFFFAOYSA-N 0.000 description 1
• 229960000103 thrombolytic agent Drugs 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 229940035936 ubiquinone Drugs 0.000 description 1
• RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 1
• 229940096973 urethral suppository Drugs 0.000 description 1
• 239000006217 urethral suppository Substances 0.000 description 1
• 229960005356 urokinase Drugs 0.000 description 1
• 230000002477 vacuolizing effect Effects 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 238000007631 vascular surgery Methods 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 238000009423 ventilation Methods 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 229960005080 warfarin Drugs 0.000 description 1
• PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 239000003064 xanthine oxidase inhibitor Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1