ES2714563T3 - Compuesto esteroideo para su uso en el tratamiento de encefalopatía hepática - Google Patents
Compuesto esteroideo para su uso en el tratamiento de encefalopatía hepática Download PDFInfo
- Publication number
- ES2714563T3 ES2714563T3 ES15705691T ES15705691T ES2714563T3 ES 2714563 T3 ES2714563 T3 ES 2714563T3 ES 15705691 T ES15705691 T ES 15705691T ES 15705691 T ES15705691 T ES 15705691T ES 2714563 T3 ES2714563 T3 ES 2714563T3
- Authority
- ES
- Spain
- Prior art keywords
- rats
- oxime
- hydroxyandrostan
- compound
- hepatic encephalopathy
- 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.)
- Active
Links
- 208000007386 hepatic encephalopathy Diseases 0.000 title claims abstract description 96
- 238000011282 treatment Methods 0.000 title claims abstract description 67
- 150000001875 compounds Chemical class 0.000 title claims description 36
- 230000003637 steroidlike Effects 0.000 title description 4
- -1 oxime compound Chemical class 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 150000002923 oximes Chemical class 0.000 claims description 129
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 66
- 229910021529 ammonia Inorganic materials 0.000 claims description 33
- 208000019423 liver disease Diseases 0.000 claims description 18
- 210000004185 liver Anatomy 0.000 claims description 14
- 230000001684 chronic effect Effects 0.000 claims description 9
- NZCRJKRKKOLAOJ-XRCRFVBUSA-N rifaximin Chemical compound OC1=C(C(O)=C2C)C3=C4N=C5C=C(C)C=CN5C4=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O NZCRJKRKKOLAOJ-XRCRFVBUSA-N 0.000 claims description 9
- 229960003040 rifaximin Drugs 0.000 claims description 9
- 208000007788 Acute Liver Failure Diseases 0.000 claims description 7
- 206010000804 Acute hepatic failure Diseases 0.000 claims description 7
- 231100000836 acute liver failure Toxicity 0.000 claims description 7
- 208000014644 Brain disease Diseases 0.000 claims description 6
- 208000032274 Encephalopathy Diseases 0.000 claims description 6
- JCQLYHFGKNRPGE-FCVZTGTOSA-N lactulose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 JCQLYHFGKNRPGE-FCVZTGTOSA-N 0.000 claims description 6
- 229960000511 lactulose Drugs 0.000 claims description 6
- PFCRQPBOOFTZGQ-UHFFFAOYSA-N lactulose keto form Natural products OCC(=O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O PFCRQPBOOFTZGQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- LRSYFEZBIMVWRY-VWMHFEHESA-N (2s)-2,5-diaminopentanoic acid;2-phenylacetic acid Chemical compound NCCC[C@H](N)C(O)=O.OC(=O)CC1=CC=CC=C1 LRSYFEZBIMVWRY-VWMHFEHESA-N 0.000 claims description 3
- 238000011260 co-administration Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229960002815 glycerol phenylbutyrate Drugs 0.000 claims description 3
- ZSDBFLMJVAGKOU-UHFFFAOYSA-N glycerol phenylbutyrate Chemical compound C=1C=CC=CC=1CCCC(=O)OCC(OC(=O)CCCC=1C=CC=CC=1)COC(=O)CCCC1=CC=CC=C1 ZSDBFLMJVAGKOU-UHFFFAOYSA-N 0.000 claims description 3
- 241000700159 Rattus Species 0.000 description 202
- 206010020575 Hyperammonaemia Diseases 0.000 description 72
- 230000000694 effects Effects 0.000 description 32
- 238000012360 testing method Methods 0.000 description 27
- 239000003981 vehicle Substances 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 102000005915 GABA Receptors Human genes 0.000 description 20
- 108010005551 GABA Receptors Proteins 0.000 description 20
- 150000003431 steroids Chemical class 0.000 description 20
- 210000004556 brain Anatomy 0.000 description 19
- 238000012549 training Methods 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 230000004973 motor coordination Effects 0.000 description 15
- 230000006886 spatial memory Effects 0.000 description 15
- 230000001154 acute effect Effects 0.000 description 14
- 230000031836 visual learning Effects 0.000 description 14
- 239000008280 blood Substances 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 238000012347 Morris Water Maze Methods 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 208000019425 cirrhosis of liver Diseases 0.000 description 11
- 230000002265 prevention Effects 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 230000037023 motor activity Effects 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 230000027288 circadian rhythm Effects 0.000 description 9
- 230000013016 learning Effects 0.000 description 9
- 230000015654 memory Effects 0.000 description 9
- 208000007232 portal hypertension Diseases 0.000 description 9
- 230000004913 activation Effects 0.000 description 8
- 210000005013 brain tissue Anatomy 0.000 description 8
- 230000007882 cirrhosis Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 208000000857 Hepatic Insufficiency Diseases 0.000 description 7
- 206010019663 Hepatic failure Diseases 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 230000003872 anastomosis Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 206010016654 Fibrosis Diseases 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 208000010877 cognitive disease Diseases 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000002440 hepatic effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 208000028698 Cognitive impairment Diseases 0.000 description 4
- 208000010334 End Stage Liver Disease Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 208000011444 chronic liver failure Diseases 0.000 description 4
- 239000008159 sesame oil Substances 0.000 description 4
- 235000011803 sesame oil Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000019430 Motor disease Diseases 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- 206010039897 Sedation Diseases 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 3
- 238000009227 behaviour therapy Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 230000007831 electrophysiology Effects 0.000 description 3
- 238000002001 electrophysiology Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000036280 sedation Effects 0.000 description 3
- 238000004088 simulation Methods 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 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
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 206010010071 Coma Diseases 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- 208000000624 Esophageal and Gastric Varices Diseases 0.000 description 2
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 206010034719 Personality change Diseases 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- 229920005372 Plexiglas® Polymers 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 208000004209 confusion Diseases 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 206010013395 disorientation Diseases 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000007788 liquid 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
- 230000003340 mental effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 229910052722 tritium Chemical group 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- ZESRJSPZRDMNHY-YFWFAHHUSA-N 11-deoxycorticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 ZESRJSPZRDMNHY-YFWFAHHUSA-N 0.000 description 1
- AURFZBICLPNKBZ-FZCSVUEKSA-N 3beta-hydroxy-5alpha-pregnan-20-one Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 AURFZBICLPNKBZ-FZCSVUEKSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 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
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- FFIBGVYTWNPLPN-FUFGZKTOSA-N C[C@](CC1)(C(CC2)C(CC3)C1[C@@](C)(CC1)C3C[C@@]1(C#C)O)/C2=N\O Chemical compound C[C@](CC1)(C(CC2)C(CC3)C1[C@@](C)(CC1)C3C[C@@]1(C#C)O)/C2=N\O FFIBGVYTWNPLPN-FUFGZKTOSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 208000005156 Dehydration Diseases 0.000 description 1
- FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 1
- 206010012335 Dependence 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
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010016275 Fear Diseases 0.000 description 1
- 102000027484 GABAA receptors Human genes 0.000 description 1
- 108091008681 GABAA receptors Proteins 0.000 description 1
- 206010051012 Gastric varices Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 206010033372 Pain and discomfort Diseases 0.000 description 1
- 201000009454 Portal vein thrombosis Diseases 0.000 description 1
- AURFZBICLPNKBZ-UHFFFAOYSA-N Pregnanolone Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(=O)C)C1(C)CC2 AURFZBICLPNKBZ-UHFFFAOYSA-N 0.000 description 1
- ORNBQBCIOKFOEO-YQUGOWONSA-N Pregnenolone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC3)C[C@@H](O)CC4)CC2)CC1 ORNBQBCIOKFOEO-YQUGOWONSA-N 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 102000007451 Steroid Receptors Human genes 0.000 description 1
- 108010085012 Steroid Receptors Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 206010056091 Varices oesophageal Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 1
- 229960005471 androstenedione Drugs 0.000 description 1
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000002457 bidirectional effect Effects 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000006227 byproduct Substances 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
- 238000004364 calculation method Methods 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 235000019993 champagne Nutrition 0.000 description 1
- 230000002060 circadian Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- ZESRJSPZRDMNHY-UHFFFAOYSA-N de-oxy corticosterone Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 ZESRJSPZRDMNHY-UHFFFAOYSA-N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
- 229940119740 deoxycorticosterone Drugs 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 208000024170 esophageal varices Diseases 0.000 description 1
- 201000010120 esophageal varix Diseases 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
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000014106 fortified food Nutrition 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000002555 ionophore Substances 0.000 description 1
- 230000000236 ionophoric effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 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
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000001095 motoneuron effect Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000003557 neuropsychological effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 102000014187 peptide receptors Human genes 0.000 description 1
- 108010011903 peptide receptors Proteins 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960002847 prasterone Drugs 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 229960000249 pregnenolone Drugs 0.000 description 1
- ORNBQBCIOKFOEO-QGVNFLHTSA-N pregnenolone Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 ORNBQBCIOKFOEO-QGVNFLHTSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000007391 self-medication Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000008454 sleep-wake cycle Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 150000003515 testosterones Chemical class 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 239000013598 vector Substances 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
- 210000001631 vena cava inferior Anatomy 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000002023 wood Substances 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7016—Disaccharides, e.g. lactose, lactulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Emergency Medicine (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Biotechnology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE1450089 | 2014-01-29 | ||
| PCT/GB2015/050060 WO2015114308A1 (en) | 2014-01-29 | 2015-01-14 | Steroid compound for use in the treatment of hepatic encephalopathy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2714563T3 true ES2714563T3 (es) | 2019-05-29 |
Family
ID=52544513
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15705691T Active ES2714563T3 (es) | 2014-01-29 | 2015-01-14 | Compuesto esteroideo para su uso en el tratamiento de encefalopatía hepática |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US20160339040A1 (https=) |
| EP (1) | EP3099306B1 (https=) |
| JP (1) | JP6543633B2 (https=) |
| KR (1) | KR102324667B1 (https=) |
| CN (2) | CN113185566A (https=) |
| AU (1) | AU2015212606B2 (https=) |
| BR (1) | BR112016017620A2 (https=) |
| CA (1) | CA2935015C (https=) |
| CY (1) | CY1121464T1 (https=) |
| DK (1) | DK3099306T3 (https=) |
| ES (1) | ES2714563T3 (https=) |
| HR (1) | HRP20190251T1 (https=) |
| HU (1) | HUE042242T2 (https=) |
| IL (1) | IL246496B (https=) |
| LT (1) | LT3099306T (https=) |
| ME (1) | ME03351B (https=) |
| MX (1) | MX2016008851A (https=) |
| PL (1) | PL3099306T3 (https=) |
| PT (1) | PT3099306T (https=) |
| RS (1) | RS58375B1 (https=) |
| RU (1) | RU2684616C2 (https=) |
| SI (1) | SI3099306T1 (https=) |
| SM (1) | SMT201900133T1 (https=) |
| TR (1) | TR201901687T4 (https=) |
| WO (1) | WO2015114308A1 (https=) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2684616C2 (ru) | 2014-01-29 | 2019-04-10 | Умекрин Когнишн Аб | Стероидное соединение для применения в лечении печеночной энцефалопатии |
| AR103384A1 (es) | 2015-01-12 | 2017-05-03 | Umecrine Cognition Ab | 3a-ETINILO, 3b-HIDROXI, 5a-PREGNAN-20-OXIMA COMO MODULADOR DE GABA |
| US10278977B2 (en) | 2016-06-06 | 2019-05-07 | Umecrine Cognition Ab | Methods for treating hypersomnolence |
| DK3668927T3 (da) | 2017-09-12 | 2024-03-25 | Eth Zuerich | Transmembran ph-gradient polymersom til kvantificering af ammoniak i kropsvæsker |
| EP3716954A1 (en) * | 2017-11-27 | 2020-10-07 | Umecrine Cognition AB | Pharmaceutical formulation of 3 -ethynyl-3 -hydroxyandrostan-17-one oxime |
| EP4079307A1 (en) | 2021-04-20 | 2022-10-26 | Umecrine Cognition AB | New medical use |
| US20230134958A1 (en) * | 2021-10-29 | 2023-05-04 | Umecrine Cognition Ab | New medical treatment |
| EP4389129A1 (en) | 2022-12-22 | 2024-06-26 | Umecrine Cognition AB | 3a-ethynyl-3beta hydroxyandrostan 17-one oxime for treating parkinson's disease and l-dopa-induced dyskinesia |
| WO2025252725A1 (en) | 2024-06-04 | 2025-12-11 | Umecrine Cognition Ab | Novel pharmaceutical formulation of golexanolone |
| WO2025252724A1 (en) | 2024-06-04 | 2025-12-11 | Umecrine Cognition Ab | Novel pharmaceutical formulation of golexanolone |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2713061A (en) | 1951-04-06 | 1955-07-12 | Schering Ag | 3-methyl androstanes |
| FR1463755A (fr) | 1960-01-26 | 1966-07-22 | Nouveaux stéroïdes de la série de l'androstane et leur procédé de préparation | |
| US3173932A (en) | 1962-11-02 | 1965-03-16 | American Cyanamid Co | 15-substituted estra-1, 3, 5(10)-trienes |
| FR2685332A1 (fr) | 1991-12-20 | 1993-06-25 | Roussel Uclaf | Nouveaux 19-nor sterouides ayant en position 11beta une chaine thiocarbonee, leur procede de preparation et les intermediaires et leur application a titre de medicaments. |
| DE69435286D1 (de) | 1993-05-24 | 2010-05-20 | Purdue Pharma Ltd | Verfahren und zusammensetzungen zum hervorrufen von schlaf |
| AU756001B2 (en) | 1998-03-11 | 2003-01-02 | Umecrine Mood Ab | Epiallopregnanolone in the treatment of CNS disorders |
| US6593321B2 (en) | 2001-06-11 | 2003-07-15 | Southwest Foundation For Biomedical Research | 2-alkoxyestradiol analogs with antiproliferative and antimitotic activity |
| GB0129260D0 (en) * | 2001-12-06 | 2002-01-23 | Eisai London Res Lab Ltd | Pharmaceutical compositions and their uses |
| SE0104423D0 (sv) * | 2001-12-27 | 2001-12-27 | Umecrine Ab | Pregnane steroids and their use in the treatment of CNS disorders |
| SI2153870T1 (sl) | 2004-11-26 | 2014-05-30 | Ucl Business Plc | Sestavki, ki obsegajo ornitin in fenilacetat ali fenilbutirat, za zdravljenje hepatitične encefalopatije |
| WO2007103162A2 (en) * | 2006-03-01 | 2007-09-13 | Samaritan Pharmaceuticals, Inc. | Structure based drug design of steroidogenesis inhibitors |
| DK2792681T3 (en) * | 2006-11-21 | 2017-01-23 | Umecrine Ab | Use of Pregnancy and Androstan Steroids in the Preparation of a Pharmaceutical Composition for the Treatment of CNS Disorders. |
| GB0711948D0 (en) | 2007-06-20 | 2007-08-01 | Bionature E A Ltd | Neurosteriod compounds |
| CN101585862B (zh) * | 2008-05-20 | 2014-12-17 | 梅克芳股份公司 | 甾族化合物 |
| HRP20200284T1 (hr) * | 2008-10-02 | 2020-07-10 | Salix Pharmaceuticals, Ltd. | Postupci liječenja hepatičke encefalopatije |
| CN104434894A (zh) | 2009-06-08 | 2015-03-25 | Ucl商业有限公司 | 使用l-鸟氨酸苯乙酸盐治疗门静脉高压和恢复肝功能 |
| WO2015048818A1 (en) | 2013-09-30 | 2015-04-02 | Hyperion Therapeutics, Inc. | Diagnosing, grading, monitoring, and treating hepatic encephalopathy |
| RU2684616C2 (ru) | 2014-01-29 | 2019-04-10 | Умекрин Когнишн Аб | Стероидное соединение для применения в лечении печеночной энцефалопатии |
-
2015
- 2015-01-14 RU RU2016127558A patent/RU2684616C2/ru active
- 2015-01-14 JP JP2016544557A patent/JP6543633B2/ja active Active
- 2015-01-14 DK DK15705691.2T patent/DK3099306T3/en active
- 2015-01-14 PT PT15705691T patent/PT3099306T/pt unknown
- 2015-01-14 LT LTEP15705691.2T patent/LT3099306T/lt unknown
- 2015-01-14 TR TR2019/01687T patent/TR201901687T4/tr unknown
- 2015-01-14 ES ES15705691T patent/ES2714563T3/es active Active
- 2015-01-14 MX MX2016008851A patent/MX2016008851A/es active IP Right Grant
- 2015-01-14 KR KR1020167023426A patent/KR102324667B1/ko active Active
- 2015-01-14 PL PL15705691T patent/PL3099306T3/pl unknown
- 2015-01-14 RS RS20190234A patent/RS58375B1/sr unknown
- 2015-01-14 EP EP15705691.2A patent/EP3099306B1/en active Active
- 2015-01-14 SM SM20190133T patent/SMT201900133T1/it unknown
- 2015-01-14 ME MEP-2019-39A patent/ME03351B/me unknown
- 2015-01-14 BR BR112016017620A patent/BR112016017620A2/pt not_active Application Discontinuation
- 2015-01-14 SI SI201530591T patent/SI3099306T1/sl unknown
- 2015-01-14 HR HRP20190251TT patent/HRP20190251T1/hr unknown
- 2015-01-14 CN CN202110480203.5A patent/CN113185566A/zh active Pending
- 2015-01-14 CA CA2935015A patent/CA2935015C/en active Active
- 2015-01-14 CN CN201580006600.1A patent/CN106163528A/zh active Pending
- 2015-01-14 WO PCT/GB2015/050060 patent/WO2015114308A1/en not_active Ceased
- 2015-01-14 US US15/114,972 patent/US20160339040A1/en not_active Abandoned
- 2015-01-14 HU HUE15705691A patent/HUE042242T2/hu unknown
- 2015-01-14 AU AU2015212606A patent/AU2015212606B2/en active Active
-
2016
- 2016-06-28 IL IL246496A patent/IL246496B/en active IP Right Grant
- 2016-11-15 US US15/352,035 patent/US9801894B2/en active Active
-
2017
- 2017-09-27 US US15/716,838 patent/US10342804B2/en active Active
-
2019
- 2019-03-12 CY CY20191100299T patent/CY1121464T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2714563T3 (es) | Compuesto esteroideo para su uso en el tratamiento de encefalopatía hepática | |
| ES2351528T3 (es) | Agonistas de orl 1/mi mixtos para el tratamiento del dolor. | |
| JP6876047B2 (ja) | ミトコンドリアの活性酸素種（ｒｏｓ）産生に関連する疾患の治療のための化合物 | |
| ES2564833T3 (es) | Composiciones farmacéuticas y métodos que utilizan un D-aminoácido y un antioxidante para tratar trastornos neuropsiquiátricos | |
| JP2017507113A5 (https=) | ||
| ES2791764T3 (es) | Composiciones de buprenorfina y antagonistas del receptor de opioides mu | |
| BRPI0706377A2 (pt) | moduladores de fator -1 induzìvel por hipoxia e usos relacionados | |
| ES2955693T3 (es) | Métodos para el tratamiento de trastornos del tracto GI | |
| ES2728870T3 (es) | Witanólidos útiles para el tratamiento de enfermedades neurodegenerativas | |
| ES2383433T3 (es) | Formulación farmacéutica de apomorfina para administración bucal | |
| BR112021001322A2 (pt) | 17 beta-heterociclil-digitalis como compostos para o tratamento de insuficiência cardíaca | |
| BR112015001989B1 (pt) | Uso de butilidenoftalida (bp) | |
| BR112013000164B1 (pt) | Agente terapêutico ou agente profilático | |
| ES2655646T3 (es) | Derivados de fentanilo como agonistas de receptores opioides dependientes del PH | |
| US20210308138A1 (en) | Tissue transglutaminase modulators for medicinal use | |
| ES3059843T3 (en) | Dhea-derived steroids | |
| ES2734066T3 (es) | Samidorfano (ALKS 33) en combinación con agonistas opioides | |
| NZ721622B2 (en) | Steroid compound for use in the treatment of hepatic encephalopathy | |
| ES2890453T3 (es) | Carbamatos de galantamina para el tratamiento del autismo | |
| HK1228753B (en) | Steroid compound for use in the treatment of hepatic encephalopathy | |
| HK1228753A1 (en) | Steroid compound for use in the treatment of hepatic encephalopathy | |
| ES2332565A1 (es) | Uso de derivados de mononitrato de dianhidrohexita como agentes antiinflamatorios. |