BRPI0609295A2 - formas cristalinas de brometo de tiotràpio, composiÇço farmacÊutica, uso e mÉtodo para preparar as mesmas - Google Patents
formas cristalinas de brometo de tiotràpio, composiÇço farmacÊutica, uso e mÉtodo para preparar as mesmas Download PDFInfo
- Publication number
- BRPI0609295A2 BRPI0609295A2 BRPI0609295-0A BRPI0609295A BRPI0609295A2 BR PI0609295 A2 BRPI0609295 A2 BR PI0609295A2 BR PI0609295 A BRPI0609295 A BR PI0609295A BR PI0609295 A2 BRPI0609295 A2 BR PI0609295A2
- Authority
- BR
- Brazil
- Prior art keywords
- crystalline
- tiotropium bromide
- solvate
- ray powder
- dried
- Prior art date
Links
- LERNTVKEWCAPOY-VOGVJGKGSA-N C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 Chemical compound C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 LERNTVKEWCAPOY-VOGVJGKGSA-N 0.000 title claims abstract description 224
- 229960000257 tiotropium bromide Drugs 0.000 title claims abstract description 222
- 238000000034 method Methods 0.000 title claims abstract description 74
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 19
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 13
- 208000006673 asthma Diseases 0.000 claims abstract description 9
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 239000012453 solvate Substances 0.000 claims description 171
- 239000000843 powder Substances 0.000 claims description 108
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 98
- 239000002904 solvent Substances 0.000 claims description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 61
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 56
- 238000010586 diagram Methods 0.000 claims description 54
- MQLXPRBEAHBZTK-SEINRUQRSA-M tiotropium bromide hydrate Chemical compound O.[Br-].C[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 MQLXPRBEAHBZTK-SEINRUQRSA-M 0.000 claims description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 46
- 239000013078 crystal Substances 0.000 claims description 44
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 42
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 41
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 34
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 33
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 33
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 claims description 30
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 29
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 29
- 229940110309 tiotropium Drugs 0.000 claims description 28
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 26
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 22
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 19
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 17
- 239000007787 solid Substances 0.000 claims description 17
- 239000007858 starting material Substances 0.000 claims description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 14
- 235000013772 propylene glycol Nutrition 0.000 claims description 14
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 239000011877 solvent mixture Substances 0.000 claims description 9
- 239000012296 anti-solvent Substances 0.000 claims description 8
- 238000012916 structural analysis Methods 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 239000004615 ingredient Substances 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000000808 adrenergic beta-agonist Substances 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 claims description 2
- 230000003454 betamimetic effect Effects 0.000 claims description 2
- JYMYVPSOAXOLGQ-UHFFFAOYSA-N dioxan-3-ol Chemical compound OC1CCCOO1 JYMYVPSOAXOLGQ-UHFFFAOYSA-N 0.000 claims description 2
- 229940121647 egfr inhibitor Drugs 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 claims description 2
- 150000003431 steroids Chemical class 0.000 claims description 2
- OEZNULIHEQCKJR-UHFFFAOYSA-N ethanol;hydrobromide Chemical compound Br.CCO OEZNULIHEQCKJR-UHFFFAOYSA-N 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 abstract description 11
- 239000000203 mixture Substances 0.000 description 63
- 239000000243 solution Substances 0.000 description 37
- 238000009472 formulation Methods 0.000 description 35
- 239000000725 suspension Substances 0.000 description 33
- 239000002775 capsule Substances 0.000 description 24
- 239000013543 active substance Substances 0.000 description 22
- -1 tiotropium bromide compound Chemical class 0.000 description 21
- 239000002245 particle Substances 0.000 description 20
- 239000003380 propellant Substances 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 238000012512 characterization method Methods 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 239000007789 gas Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 11
- 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 10
- 239000000443 aerosol Substances 0.000 description 10
- 229960001375 lactose Drugs 0.000 description 10
- 239000008101 lactose Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- 239000004698 Polyethylene Substances 0.000 description 8
- 229960001021 lactose monohydrate Drugs 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 229920000573 polyethylene Polymers 0.000 description 8
- 238000000634 powder X-ray diffraction Methods 0.000 description 7
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 238000002441 X-ray diffraction Methods 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 229920003023 plastic Polymers 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 4
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- CRSOQBOWXPBRES-UHFFFAOYSA-N neopentane Chemical compound CC(C)(C)C CRSOQBOWXPBRES-UHFFFAOYSA-N 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Inorganic materials [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- GVLGAFRNYJVHBC-UHFFFAOYSA-N hydrate;hydrobromide Chemical compound O.Br GVLGAFRNYJVHBC-UHFFFAOYSA-N 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- KSHXTPINHVBHGH-UHFFFAOYSA-N 2-ethyl-2-hydroxyhexanoic acid Chemical compound CCCCC(O)(CC)C(O)=O KSHXTPINHVBHGH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 244000246386 Mentha pulegium Species 0.000 description 2
- 235000016257 Mentha pulegium Nutrition 0.000 description 2
- 235000004357 Mentha x piperita Nutrition 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- 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 2
- 239000001273 butane Substances 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- RWRIWBAIICGTTQ-UHFFFAOYSA-N difluoromethane Chemical compound FCF RWRIWBAIICGTTQ-UHFFFAOYSA-N 0.000 description 2
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
- 150000002016 disaccharides Chemical class 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 235000001050 hortel pimenta Nutrition 0.000 description 2
- 238000001746 injection moulding Methods 0.000 description 2
- 239000001282 iso-butane Substances 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229940068977 polysorbate 20 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- ARIWANIATODDMH-UHFFFAOYSA-N rac-1-monolauroylglycerol Chemical compound CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 1
- HDIFHQMREAYYJW-FMIVXFBMSA-N 2,3-dihydroxypropyl (e)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C\CCCCCCCC(=O)OCC(O)CO HDIFHQMREAYYJW-FMIVXFBMSA-N 0.000 description 1
- OTVGARFFAAFRAC-UHFFFAOYSA-N 2-bromo-1,4-dioxane Chemical compound BrC1COCCO1 OTVGARFFAAFRAC-UHFFFAOYSA-N 0.000 description 1
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 235000007516 Chrysanthemum Nutrition 0.000 description 1
- 244000189548 Chrysanthemum x morifolium Species 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 1
- 240000006927 Foeniculum vulgare Species 0.000 description 1
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical group Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 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
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-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)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 HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- NFCRBQADEGXVDL-UHFFFAOYSA-M cetylpyridinium chloride monohydrate Chemical compound O.[Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NFCRBQADEGXVDL-UHFFFAOYSA-M 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 229910052593 corundum Inorganic materials 0.000 description 1
- 239000010431 corundum Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011152 fibreglass Substances 0.000 description 1
- 229940068939 glyceryl monolaurate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- ZEZKMMFYTLTLJS-UHFFFAOYSA-N methanol;hydrobromide Chemical compound Br.OC ZEZKMMFYTLTLJS-UHFFFAOYSA-N 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 239000006082 mold release agent Substances 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000007971 pharmaceutical suspension Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 229940117972 triolein Drugs 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms
- C07D451/10—Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67680705P | 2005-05-02 | 2005-05-02 | |
| US60/676,807 | 2005-05-02 | ||
| PCT/EP2006/061763 WO2006117299A2 (en) | 2005-05-02 | 2006-04-21 | Novel crystalline forms of tiotropium bromide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0609295A2 true BRPI0609295A2 (pt) | 2010-03-23 |
Family
ID=36693210
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0609295-0A BRPI0609295A2 (pt) | 2005-05-02 | 2006-04-21 | formas cristalinas de brometo de tiotràpio, composiÇço farmacÊutica, uso e mÉtodo para preparar as mesmas |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7879871B2 (enExample) |
| EP (2) | EP2085396A3 (enExample) |
| JP (1) | JP5227790B2 (enExample) |
| KR (1) | KR20080012932A (enExample) |
| CN (1) | CN101166738B (enExample) |
| AR (1) | AR053599A1 (enExample) |
| AU (1) | AU2006243238B2 (enExample) |
| BR (1) | BRPI0609295A2 (enExample) |
| CA (1) | CA2606549A1 (enExample) |
| DK (1) | DK1881980T3 (enExample) |
| ES (1) | ES2393794T3 (enExample) |
| IL (1) | IL187055A (enExample) |
| MX (1) | MX2007013142A (enExample) |
| NZ (1) | NZ563596A (enExample) |
| PE (1) | PE20061438A1 (enExample) |
| PL (1) | PL1881980T3 (enExample) |
| PT (1) | PT1881980E (enExample) |
| RU (1) | RU2417224C2 (enExample) |
| SI (1) | SI1881980T1 (enExample) |
| TW (1) | TWI392674B (enExample) |
| UY (1) | UY29506A1 (enExample) |
| WO (1) | WO2006117299A2 (enExample) |
| ZA (1) | ZA200708048B (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9108962B2 (en) | 2005-12-19 | 2015-08-18 | Sicor, Inc. | Forms of tiotropium bromide and processes for preparation thereof |
| PT1869035E (pt) | 2005-12-19 | 2013-01-10 | Sicor Inc | Novas formas de brometo de tiotrópio e processos para sua preparação |
| TW200734333A (en) * | 2005-12-19 | 2007-09-16 | Sicor Inc | Pure and stable tiotropium bromide |
| CN100999521B (zh) * | 2006-01-13 | 2010-12-08 | 江苏正大天晴药业股份有限公司 | 结晶性抗胆碱药噻托溴铵 |
| US20080051582A1 (en) | 2006-07-10 | 2008-02-28 | Sicor Inc. | Process for the preparation of tiotropium bromide |
| EP1923393A1 (en) * | 2006-11-17 | 2008-05-21 | Boehringer Ingelheim Pharma GmbH & Co. KG | Crystalline form of tiotropium bromide and urea |
| GB0716026D0 (en) * | 2007-08-16 | 2007-09-26 | Norton Healthcare Ltd | An inhalable medicament |
| CN105601628A (zh) * | 2008-01-10 | 2016-05-25 | 基因里克斯(英国)有限公司 | 用于制备东莨菪醇酯的方法 |
| NZ592861A (en) * | 2008-11-04 | 2013-01-25 | Cipla Ltd | Pharmaceutical aerosol composition |
| JP5650120B2 (ja) * | 2008-11-04 | 2015-01-07 | シプラ・リミテッド | 低い結晶化度を有する臭化チオトロピウム |
| EP2403851B1 (en) | 2009-03-06 | 2015-06-17 | Mahmut Bilgic | New crystalline forms of tiotropium bromide |
| EP2462140A2 (en) * | 2009-08-07 | 2012-06-13 | Generics [UK] Limited | Anhydrate of triotropium bromide |
| WO2011015883A1 (en) | 2009-08-07 | 2011-02-10 | Generics [Uk] Limited | Dichloromethane solvate of tiotropium bromide and its use |
| TR201007108A2 (tr) * | 2010-08-25 | 2012-03-21 | B�Lg�� Mahmut | Yeni tiotropyum bromür kristali ve üretim yöntemi.@ |
| TR201111589A2 (tr) * | 2011-03-03 | 2012-09-21 | Bi̇lgi̇ç Mahmut | Tiotropyum bromür susuz kristal formu. |
| TR201102068A2 (tr) | 2011-03-03 | 2012-09-21 | Bi̇lgi̇ç Mahmut | Tiotropyum bromür içeren kristal maddeler |
| CZ304368B6 (cs) | 2011-11-28 | 2014-04-02 | Zentiva, K.S. | Směsný solvát tiotropium bromidu a způsob jeho přípravy |
| GB201200525D0 (en) | 2011-12-19 | 2012-02-29 | Teva Branded Pharmaceutical Prod R & D Inc | An inhalable medicament |
| PT106142B (pt) | 2012-02-10 | 2014-07-18 | Hovione Farmaci Ncia S A | Processo para a preparação de brometo de tiotrópio |
| EP2897955B1 (en) * | 2012-09-11 | 2019-11-06 | Bilgic, Mahmut | New tiotropium bromide crystalline form |
| ES2620758T3 (es) * | 2012-11-05 | 2017-06-29 | Zentiva K.S. | Estabilización de solvatos de tiotropio |
| EP2981247B1 (en) | 2013-04-01 | 2023-06-07 | Pulmatrix Operating Company, Inc. | Tiotropium dry powders |
| EP2913332A1 (en) * | 2014-02-27 | 2015-09-02 | Euticals S.P.A. | Crystalline form of tiotropium bromide with lactose |
| US10034866B2 (en) | 2014-06-19 | 2018-07-31 | Teva Branded Pharmaceutical Products R&D, Inc. | Inhalable medicament comprising tiotropium |
| WO2017138896A1 (en) * | 2016-02-11 | 2017-08-17 | Sima Patent Ve Lisanslama Hizmetleri Ltd. Şti | Crystalline form of tiotropium bromide anhydrate |
| PT115583B (pt) | 2019-06-17 | 2022-05-02 | Hovione Farm S A | Processo contínuo para a preparação de medicamentos anticolinérgicos |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB845056A (en) | 1957-07-05 | 1960-08-17 | Egyt Gyogyszervegyeszeti Gyar | Improvements in or relating to tropane derivatives |
| DE1166787B (de) | 1960-07-09 | 1964-04-02 | Boehringer & Soehne Gmbh | Verfahren zur Herstellung von neuen Granatanol-(3ª‰)-estern und ihren Hydrohalogeniden |
| GB955535A (en) | 1962-10-22 | 1964-04-15 | Boehringer & Soehne Gmbh | New n-substituted norgranatanol-(3ª‰)-esters |
| DE2046659A1 (enExample) | 1970-01-28 | 1972-03-23 | ||
| US3808263A (en) | 1970-05-12 | 1974-04-30 | Tanabe Seiyaku Co | 6,6-dimethyl-9-alkyl-9-azabicyclo(3.3.1)nonan-3-ols |
| US3673195A (en) | 1970-05-25 | 1972-06-27 | Tanabe Seiyaku Co | Derivatives of 6,6,9-tri-lower alkyl-9-azabicyclo(3.3.1) nonan-3{60 -or 3{62 -ol |
| US4353922A (en) | 1981-03-13 | 1982-10-12 | Syntex (U.S.A.) Inc. | Anticholinergic bronchodilators |
| US4570630A (en) | 1983-08-03 | 1986-02-18 | Miles Laboratories, Inc. | Medicament inhalation device |
| FI88112C (fi) | 1985-07-30 | 1993-04-13 | Glaxo Group Ltd | Anordning foer administrering av laekemedel till patienter |
| DE3546218A1 (de) | 1985-12-27 | 1987-07-02 | Madaus & Co Dr | Azoniaspironortropanolester, verfahren zu deren herstellung und pharmazeutisches mittel |
| DE3931041C2 (de) | 1989-09-16 | 2000-04-06 | Boehringer Ingelheim Kg | Ester von Thienylcarbonsäuren mit Aminoalkoholen, ihre Quaternierungsprodukte, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
| US5610163A (en) | 1989-09-16 | 1997-03-11 | Boehringer Ingelheim Gmbh | Esters of thienyl carboxylic acids and amino alcohols and their quaternization products |
| US5770738A (en) | 1992-03-05 | 1998-06-23 | Boehringer Ingelheim Kg | Esters of bi- and tricyclic amino alcohols, their preparation and their use in pharmaceutical compositions |
| DK0673240T3 (da) | 1992-12-09 | 1999-10-11 | Boehringer Ingelheim Pharma | Stabiliserede medicinske aerosolopløsningsformuleringer |
| DE4318455A1 (de) | 1993-06-03 | 1994-12-08 | Boehringer Ingelheim Kg | Kapselhalterung |
| AU749697B2 (en) | 1998-08-04 | 2002-07-04 | Jagotec Ag | Medicinal aerosol formulations |
| DE19921693A1 (de) | 1999-05-12 | 2000-11-16 | Boehringer Ingelheim Pharma | Neuartige Arzneimittelkompositionen auf der Basis von anticholinergisch wirksamen Verbindungen und ß-Mimetika |
| US6908928B2 (en) * | 2000-10-12 | 2005-06-21 | Bi Pharma Kg. | Crystalline tiotropium bromide monohydrate, processes for the preparation thereof, and pharmaceutical compositions |
| OA12522A (en) * | 2000-10-12 | 2006-05-30 | Boehringer Ingelheim Pharma | Novel tiotropium-containing inhalation powder. |
| UA75375C2 (en) | 2000-10-12 | 2006-04-17 | Boehringer Ingelheim Pharma | Method for producing powdery preparations for inhaling |
| AU2002214996B2 (en) | 2000-10-12 | 2007-03-15 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Crystalline monohydrate, method for producing the same and the use thereof in the production of a medicament |
| EE05314B1 (et) | 2000-10-31 | 2010-08-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Tiotroopiumsoola sisaldav inhaleeritav lahusekompositsioon |
| US20020111363A1 (en) | 2000-10-31 | 2002-08-15 | Karin Drechsel | Inhalable formulation of a solution containing a tiotropium salt |
| DE10056104A1 (de) | 2000-11-13 | 2002-05-23 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Tiotropiumsalzen und Salzen des Salmeterols |
| US20020193392A1 (en) | 2000-11-13 | 2002-12-19 | Christel Schmelzer | Pharmaceutical compositions based on tiotropium salts of salts of salmeterol |
| DE10064816A1 (de) | 2000-12-22 | 2002-06-27 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung eines Anticholinergikums |
| US6506900B1 (en) | 2001-01-31 | 2003-01-14 | Boehringer Ingelheim Pharma Ag | Process for preparing a scopine ester intermediate |
| US20020193394A1 (en) | 2001-03-13 | 2002-12-19 | Bernd Disse | Compounds for treating inflammatory diseases |
| DE10111843A1 (de) | 2001-03-13 | 2002-09-19 | Boehringer Ingelheim Pharma | Verbindungen zur Behandlung von inflammatorischen Erkrankungen |
| SK287262B6 (sk) * | 2001-06-22 | 2010-04-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Kryštalický bezvodný tiotropiumbromid, spôsob jeho výroby, farmaceutický prostriedok s jeho obsahom a jeho použitie |
| US6608055B2 (en) * | 2001-06-22 | 2003-08-19 | Boehringer Ingelheim Pharma Kg | Crystalline anticholinergic, processes for preparing it and its use for preparing a pharmaceutical composition |
| GB0118373D0 (en) * | 2001-07-27 | 2001-09-19 | Glaxo Group Ltd | Novel therapeutic method |
| DE10200943A1 (de) | 2002-01-12 | 2003-07-24 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Scopinestern |
| US20030229227A1 (en) | 2002-03-16 | 2003-12-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | New difurylglycolic acid esters, processes for the preparation thereof as well as the use thereof as pharmaceutical compositions |
| US7309707B2 (en) | 2002-03-20 | 2007-12-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Crystalline micronisate, process for the manufacture thereof and use thereof for the preparation of a medicament |
| DE10212264A1 (de) | 2002-03-20 | 2003-10-02 | Boehringer Ingelheim Pharma | Kristallines Mikronisat, Verfahren zu dessen Herstellung und dessen Verwendung zur Herstellung eines Arzneimittels |
| DE10214264A1 (de) * | 2002-03-28 | 2003-10-16 | Boehringer Ingelheim Pharma | HFA-Suspensionsformulierungen eines Anhydrats |
| US7244415B2 (en) * | 2002-03-28 | 2007-07-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | HFA suspension formulations of an anhydrate |
| US7311894B2 (en) | 2002-03-28 | 2007-12-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | HFA suspension formulations containing an anticholinergic |
| AU2003303029A1 (en) * | 2002-12-16 | 2004-07-09 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Tiotropium containing hfc solution formulations |
| US7968717B2 (en) | 2003-11-03 | 2011-06-28 | Boehringer Ingelhein International Gmbh | Crystalline anhydrate with anticholinergic efficacy |
| DE102004041253A1 (de) | 2004-08-26 | 2006-03-02 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neues Verfahren zur Herstellung von Tiotropiumsalzen |
-
2006
- 2006-04-21 PL PL06754794T patent/PL1881980T3/pl unknown
- 2006-04-21 EP EP09157096A patent/EP2085396A3/en not_active Withdrawn
- 2006-04-21 SI SI200631474T patent/SI1881980T1/sl unknown
- 2006-04-21 PT PT67547943T patent/PT1881980E/pt unknown
- 2006-04-21 CN CN2006800142275A patent/CN101166738B/zh active Active
- 2006-04-21 RU RU2007144521/04A patent/RU2417224C2/ru active
- 2006-04-21 DK DK06754794.3T patent/DK1881980T3/da active
- 2006-04-21 BR BRPI0609295-0A patent/BRPI0609295A2/pt not_active IP Right Cessation
- 2006-04-21 WO PCT/EP2006/061763 patent/WO2006117299A2/en not_active Ceased
- 2006-04-21 ES ES06754794T patent/ES2393794T3/es active Active
- 2006-04-21 KR KR1020077028139A patent/KR20080012932A/ko not_active Ceased
- 2006-04-21 CA CA002606549A patent/CA2606549A1/en not_active Abandoned
- 2006-04-21 JP JP2008509408A patent/JP5227790B2/ja active Active
- 2006-04-21 EP EP06754794A patent/EP1881980B1/en active Active
- 2006-04-21 NZ NZ563596A patent/NZ563596A/en not_active IP Right Cessation
- 2006-04-21 AU AU2006243238A patent/AU2006243238B2/en not_active Ceased
- 2006-04-28 UY UY29506A patent/UY29506A1/es not_active Application Discontinuation
- 2006-04-28 PE PE2006000456A patent/PE20061438A1/es not_active Application Discontinuation
- 2006-04-28 TW TW095115408A patent/TWI392674B/zh not_active IP Right Cessation
- 2006-04-28 AR ARP060101714A patent/AR053599A1/es unknown
- 2006-05-01 US US11/381,076 patent/US7879871B2/en active Active
- 2006-12-07 MX MX2007013142A patent/MX2007013142A/es active IP Right Grant
-
2007
- 2007-09-19 ZA ZA200708048A patent/ZA200708048B/xx unknown
- 2007-10-31 IL IL187055A patent/IL187055A/en active IP Right Grant
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BRPI0609295A2 (pt) | formas cristalinas de brometo de tiotràpio, composiÇço farmacÊutica, uso e mÉtodo para preparar as mesmas | |
| KR101285571B1 (ko) | 항콜린성 효과를 지닌 신규한 무수 결정 | |
| BRPI0611091A2 (pt) | formas cristalinas de brometo de tiotrópico | |
| US7968717B2 (en) | Crystalline anhydrate with anticholinergic efficacy | |
| ZA200602343B (en) | Novel tiotropium salts, methods for the production thereof, and pharmaceutical formulations containing the same | |
| PT2067779E (pt) | Sais de tiotrópio, processo para a sua preparação e formulações de produtos farmacêuticos contendo os mesmos | |
| HK1114856B (en) | Novel crystalline forms of tiotropium bromide | |
| HK1099752B (en) | Novel crystalline anhydrate with anticholinergic effect |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] | ||
| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |