ES2343444T3 - Sales de benzodiazepina de actuacion corta y sus formas polimorficas. - Google Patents
Sales de benzodiazepina de actuacion corta y sus formas polimorficas. Download PDFInfo
- Publication number
- ES2343444T3 ES2343444T3 ES07733519T ES07733519T ES2343444T3 ES 2343444 T3 ES2343444 T3 ES 2343444T3 ES 07733519 T ES07733519 T ES 07733519T ES 07733519 T ES07733519 T ES 07733519T ES 2343444 T3 ES2343444 T3 ES 2343444T3
- Authority
- ES
- Spain
- Prior art keywords
- salt
- salt according
- compound
- formula
- subject
- 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
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical class N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 110
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 35
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical class CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 13
- 230000000147 hypnotic effect Effects 0.000 claims abstract description 13
- 239000003158 myorelaxant agent Substances 0.000 claims abstract description 8
- 239000001961 anticonvulsive agent Substances 0.000 claims abstract description 7
- 239000002249 anxiolytic agent Substances 0.000 claims abstract description 7
- 230000000949 anxiolytic effect Effects 0.000 claims abstract description 7
- 239000000932 sedative agent Substances 0.000 claims abstract description 7
- 230000001624 sedative effect Effects 0.000 claims abstract description 7
- 230000001773 anti-convulsant effect Effects 0.000 claims abstract description 4
- 229960003965 antiepileptics Drugs 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 103
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 84
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- 239000002904 solvent Substances 0.000 claims description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 206010039897 Sedation Diseases 0.000 claims description 11
- 239000012458 free base Substances 0.000 claims description 11
- 230000036280 sedation Effects 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- 229950007655 esilate Drugs 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 206010010904 Convulsion Diseases 0.000 claims description 6
- 239000002244 precipitate Substances 0.000 claims description 6
- 206010021118 Hypotonia Diseases 0.000 claims description 5
- -1 MtBE Chemical compound 0.000 claims description 5
- 230000006698 induction Effects 0.000 claims description 5
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 5
- 229940011051 isopropyl acetate Drugs 0.000 claims description 5
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 5
- 230000036640 muscle relaxation Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 239000012296 anti-solvent Substances 0.000 claims description 3
- 239000006184 cosolvent Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 1
- 230000003387 muscular Effects 0.000 claims 1
- 235000002639 sodium chloride Nutrition 0.000 description 92
- 238000000634 powder X-ray diffraction Methods 0.000 description 29
- 239000000243 solution Substances 0.000 description 19
- 239000007787 solid Substances 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 230000037396 body weight Effects 0.000 description 8
- 230000007613 environmental effect Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 230000035800 maturation Effects 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000000113 differential scanning calorimetry Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000005755 formation reaction Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 238000002411 thermogravimetry Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229940125681 anticonvulsant agent Drugs 0.000 description 3
- 229940005530 anxiolytics Drugs 0.000 description 3
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 229940035363 muscle relaxants Drugs 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- NZAQRZWBQUIBSF-UHFFFAOYSA-N 4-(4-sulfobutoxy)butane-1-sulfonic acid Chemical compound OS(=O)(=O)CCCCOCCCCS(O)(=O)=O NZAQRZWBQUIBSF-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000003109 amnesic effect Effects 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003874 central nervous system depressant Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000008380 degradant Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010931 ester hydrolysis Methods 0.000 description 2
- 150000002148 esters Chemical group 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002695 general anesthesia Methods 0.000 description 2
- 239000003193 general anesthetic agent Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000003918 potentiometric titration Methods 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- XUSKJHCMMWAAHV-SANMLTNESA-N 220913-32-6 Chemical compound C1=C(O)C=C2C([Si](C)(C)C(C)(C)C)=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 XUSKJHCMMWAAHV-SANMLTNESA-N 0.000 description 1
- 229910000809 Alumel Inorganic materials 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229940008309 acetone / ethanol Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000005280 amorphization Methods 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 235000019506 cigar Nutrition 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000011152 fibreglass Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 229960001269 glycine hydrochloride Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 230000014759 maintenance of location Effects 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
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000012803 optimization experiment Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000001907 polarising light microscopy Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000004799 sedative–hypnotic effect Effects 0.000 description 1
- 239000004460 silage Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0613693 | 2006-07-10 | ||
| GBGB0613693.1A GB0613693D0 (en) | 2006-07-10 | 2006-07-10 | Benzodiazepine salts (3) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2343444T3 true ES2343444T3 (es) | 2010-07-30 |
Family
ID=36926778
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07733519T Active ES2343444T3 (es) | 2006-07-10 | 2007-07-10 | Sales de benzodiazepina de actuacion corta y sus formas polimorficas. |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US8642588B2 (enExample) |
| EP (1) | EP2089378B1 (enExample) |
| JP (1) | JP5394238B2 (enExample) |
| AT (1) | ATE461927T1 (enExample) |
| CA (1) | CA2657369C (enExample) |
| DE (1) | DE602007005515D1 (enExample) |
| ES (1) | ES2343444T3 (enExample) |
| GB (1) | GB0613693D0 (enExample) |
| WO (1) | WO2008007081A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20170091770A (ko) | 2006-07-10 | 2017-08-09 | 파이온 유케이 리미티드 | 속효형 벤조디아제핀 염 및 이의 중합체 형태 |
| EP2305647A1 (en) | 2009-09-18 | 2011-04-06 | PAION UK Limited | Process for preparing 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4 H-imidazo[1,2-a][1,4]benzodiazepine-4-yl] propionic acid methyl ester or the benzene sulfonate salt thereof, and compounds useful in that process |
| EP2450039A1 (en) | 2010-11-08 | 2012-05-09 | PAION UK Ltd. | Dosing regimen for sedation with CNS 7056 (Remimazolam) |
| CN102964349A (zh) * | 2011-08-31 | 2013-03-13 | 江苏恒瑞医药股份有限公司 | 苯并二氮杂*衍生物的托西酸盐及其多晶型、它们的制备方法和用途 |
| CN104968348B (zh) | 2012-05-22 | 2018-04-17 | Paion英国有限公司 | 包含短效苯二氮杂*类化合物的组合物 |
| DK2891494T3 (da) | 2012-08-31 | 2023-10-23 | Paion Uk Ltd | Fremgangsmåde til administration af hypnotisserende/beroligende midler |
| AR094963A1 (es) * | 2013-03-04 | 2015-09-09 | Ono Pharmaceutical Co | Reacción de oxidación excelente en el índice de conversión |
| CN103202815B (zh) * | 2013-05-05 | 2014-09-24 | 李友香 | 治疗精神疾病的注射剂 |
| CN103232454A (zh) * | 2013-05-05 | 2013-08-07 | 王元青 | 治疗精神疾病的药物 |
| CN104146970A (zh) * | 2013-05-05 | 2014-11-19 | 王元青 | 治疗精神疾病的冻干粉针剂 |
| CN103230595B (zh) * | 2013-05-05 | 2014-10-08 | 李友香 | 治疗精神疾病的组合物 |
| CN106632342B (zh) * | 2015-08-07 | 2019-01-25 | 成都倍特药业有限公司 | 苯并二氮杂*衍生物的2-萘磺酸盐及晶型和它们的制备方法 |
| WO2017178663A1 (en) | 2016-04-14 | 2017-10-19 | Paion Uk Limited | Orally inhaled and nasal benzodiazepines |
| CN108503644B (zh) * | 2016-12-09 | 2019-06-14 | 成都倍特药业有限公司 | 一种苯并二氮杂*衍生物的氢溴酸盐及其制备方法和用途 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3933794A (en) * | 1971-08-04 | 1976-01-20 | The Upjohn Company | 2-(2-Alkynylamino)-3H-1,4-benzodiazepines |
| US4724237A (en) | 1984-06-26 | 1988-02-09 | Merck & Co., Inc. | 2-substituted-aminomethyl-1,4-benzodiazepines |
| US5019583A (en) * | 1989-02-15 | 1991-05-28 | Glaxo Inc. | N-phenyl-N-(4-piperidinyl)amides useful as analgesics |
| AU678503B2 (en) * | 1993-09-24 | 1997-05-29 | Takeda Chemical Industries Ltd. | Condensed heterocyclic compounds and their use as squalene synthetase inhibitors |
| CA2143246C (en) * | 1994-03-16 | 2000-08-22 | Thierry Godel | Imidazodiazepines |
| US5834464A (en) * | 1994-11-18 | 1998-11-10 | Merck & Co., Inc. | Imidazolinobenzodiazepines |
| WO1996020941A1 (de) | 1995-01-06 | 1996-07-11 | F. Hoffmann-La Roche Ag | Hydroxymethyl-imidazodiazepine und deren ester |
| AU4382896A (en) | 1995-02-02 | 1996-08-21 | F. Hoffmann-La Roche Ag | Acetylimidazobenzodiazepines |
| GB9911152D0 (en) | 1999-05-14 | 1999-07-14 | Glaxo Group Ltd | Short-acting benzodiazepines |
| US7160880B1 (en) * | 1999-05-14 | 2007-01-09 | Cenes Limited | Short-acting benzodiazepines |
| SI21850A (sl) * | 2004-07-28 | 2006-02-28 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Soli olanzapina in njihova pretvorba v prosto bazo olanzapina |
| KR20170091770A (ko) | 2006-07-10 | 2017-08-09 | 파이온 유케이 리미티드 | 속효형 벤조디아제핀 염 및 이의 중합체 형태 |
-
2006
- 2006-07-10 GB GBGB0613693.1A patent/GB0613693D0/en not_active Ceased
-
2007
- 2007-07-10 EP EP07733519A patent/EP2089378B1/en active Active
- 2007-07-10 DE DE602007005515T patent/DE602007005515D1/de active Active
- 2007-07-10 CA CA2657369A patent/CA2657369C/en active Active
- 2007-07-10 US US12/373,457 patent/US8642588B2/en active Active
- 2007-07-10 JP JP2009518957A patent/JP5394238B2/ja active Active
- 2007-07-10 WO PCT/GB2007/002583 patent/WO2008007081A1/en not_active Ceased
- 2007-07-10 ES ES07733519T patent/ES2343444T3/es active Active
- 2007-07-10 AT AT07733519T patent/ATE461927T1/de active
Also Published As
| Publication number | Publication date |
|---|---|
| US20100075955A1 (en) | 2010-03-25 |
| JP5394238B2 (ja) | 2014-01-22 |
| CA2657369C (en) | 2014-12-09 |
| EP2089378A1 (en) | 2009-08-19 |
| JP2009542787A (ja) | 2009-12-03 |
| DE602007005515D1 (de) | 2010-05-06 |
| CA2657369A1 (en) | 2008-01-17 |
| EP2089378B1 (en) | 2010-03-24 |
| GB0613693D0 (en) | 2006-08-16 |
| US8642588B2 (en) | 2014-02-04 |
| WO2008007081A1 (en) | 2008-01-17 |
| ATE461927T1 (de) | 2010-04-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2343444T3 (es) | Sales de benzodiazepina de actuacion corta y sus formas polimorficas. | |
| ES2352360T3 (es) | Sales de benzodiazepina de actuación corta y sus formas polimórficas. | |
| ES2705063T3 (es) | Un cristal que comprende una sal de ácido L-málico de N-[2-(dietilamino)etil]-5-[(5-fluoro-1,2-dihidro-2-oxo-3H-indol-3-iliden)metil]-2,4-dimetil-1H-pirrol-3-carboxamida para su uso como un medicamento | |
| US12365684B2 (en) | Short-acting benzodiazepine salts and their polymorphic forms | |
| ES2552386T3 (es) | Composiciones de {3-[5-(4-cloro-fenil)-1H-pirrol[2,3-b]piridin-3-carbonil]-2,4-difluoro-fenil}-amida del ácido propano-1-sulfónico y usos de las mismas | |
| BR112014028841B1 (pt) | Formas cristalinas 1 e 2, composição farmacêutica, uso da forma cristalina 1 para o tratamento de um estado de doença tratável pela inibição de alk e processo para a preparação de n-[5-(3,5-difluoro-benzil)-1h-indazol-3-il]-4-(4-metilpiperazin-1-il)-2-(tetra-hidro-piran-4-ilamino)- benzamida | |
| AU2008334924A1 (en) | Solid forms of Tenofovir disoproxil | |
| AU2021203085B2 (en) | Crystalline forms of quinolone analogs and their salts | |
| ES2766324T3 (es) | Formas salinas de Alfa-TEA: composiciones y usos para tratar enfermedades | |
| US20170166590A1 (en) | Crystalline forms of quinolone analogs and their salts | |
| ES3016818T3 (en) | Co-crystal of ketoprofen and its preparation, pharmaceutical compositions comprising the same and uses thereof | |
| CA3239187A1 (en) | Mono-p-toluenesulfonate of axl kinase inhibitor and crystal form thereof | |
| AU2010319349A1 (en) | Crystalline forms of neurotrophin mimetic compounds and their salts | |
| JP2013529224A (ja) | 結晶性エザチオスタット塩酸塩非溶媒和物 | |
| CN111918859B (zh) | 稠合三环γ-氨基酸衍生物的盐的晶型及制备和应用 | |
| ES2893424T3 (es) | Sal de derivado de cefalosporina, su forma sólida cristalina y método para producirla | |
| JPH11513402A (ja) | モルヒネ−６−グルクロニドの新しい結晶形態 | |
| CN108948018B (zh) | 苯并二氮*衍生物及其盐和相关晶体形式、制备方法和用途 | |
| RU2802964C2 (ru) | Твердые формы 2-(5-(4-(2-морфолиноэтокси)фенил)пиридин-2-ил)-n-бензилацетамида | |
| ES2389589T3 (es) | Sal de fumarato de 1,4-diazabiciclo[3.2.2]nonano-4-carboxilato de 4-bromefelino, sus formas cristalinas, su preparación y su utilización en terapéutica | |
| HK40098923A (en) | Crystalline forms of quinolone analogs and their salts | |
| BR112015030751B1 (pt) | Formas polimórficas de icotinib e usos das mesmas | |
| HK1253589A1 (zh) | 一种苯并二氮杂䓬衍生物的氢溴酸盐及其制备方法和用途 | |
| ES2656699T9 (es) | Formas polimorfas de maleato de Icotinib y utilizaciones de las mismas | |
| HK1262858A1 (en) | Salt of quinazoline derivative-like tyrosine kinase inhibitor and crystal form thereof |