MX2007015997A - Procedimiento para preparar nuevas sales de tiotropio, nuevas sales de tiotropio como tales y composiciones farmaceuticas de las mismas. - Google Patents
Procedimiento para preparar nuevas sales de tiotropio, nuevas sales de tiotropio como tales y composiciones farmaceuticas de las mismas.Info
- Publication number
- MX2007015997A MX2007015997A MX2007015997A MX2007015997A MX2007015997A MX 2007015997 A MX2007015997 A MX 2007015997A MX 2007015997 A MX2007015997 A MX 2007015997A MX 2007015997 A MX2007015997 A MX 2007015997A MX 2007015997 A MX2007015997 A MX 2007015997A
- Authority
- MX
- Mexico
- Prior art keywords
- crystalline
- amino
- optionally substituted
- phenyl
- quinazoline
- Prior art date
Links
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical class 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 title claims abstract description 122
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 64
- 238000004519 manufacturing process Methods 0.000 title abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 39
- -1 heterocyclyl sulfonate Chemical class 0.000 claims description 337
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 153
- 239000000843 powder Substances 0.000 claims description 128
- 150000003839 salts Chemical class 0.000 claims description 103
- 229940110309 tiotropium Drugs 0.000 claims description 85
- 238000000034 method Methods 0.000 claims description 81
- 239000002904 solvent Substances 0.000 claims description 64
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 61
- 239000002253 acid Substances 0.000 claims description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 54
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 48
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 47
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 44
- 238000010586 diagram Methods 0.000 claims description 40
- 239000007787 solid Substances 0.000 claims description 38
- 239000013078 crystal Substances 0.000 claims description 35
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 34
- 230000008569 process Effects 0.000 claims description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 29
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 26
- 238000012916 structural analysis Methods 0.000 claims description 26
- 150000004682 monohydrates Chemical class 0.000 claims description 25
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 24
- 239000012453 solvate Substances 0.000 claims description 21
- 150000004677 hydrates Chemical class 0.000 claims description 19
- 229960001860 salicylate Drugs 0.000 claims description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 18
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 17
- 230000002062 proliferating effect Effects 0.000 claims description 17
- 150000001450 anions Chemical class 0.000 claims description 15
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 14
- 238000002441 X-ray diffraction Methods 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 229940095064 tartrate Drugs 0.000 claims description 14
- 229950000339 xinafoate Drugs 0.000 claims description 14
- 150000001298 alcohols Chemical class 0.000 claims description 13
- 238000004458 analytical method Methods 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 239000003112 inhibitor Substances 0.000 claims description 13
- 208000023504 respiratory system disease Diseases 0.000 claims description 13
- 208000024891 symptom Diseases 0.000 claims description 13
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000003456 ion exchange resin Substances 0.000 claims description 11
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 11
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 10
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 150000004820 halides Chemical class 0.000 claims description 9
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 9
- 230000002452 interceptive effect Effects 0.000 claims description 9
- HVIDCXBJDYXPTO-JAZONYGRSA-M tiotropium salicylate Chemical compound OC(=O)C1=CC=CC=C1[O-].C([C@H]1[N+]([C@H](C2)[C@H]3[C@@H]1O3)(C)C)C2OC(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 HVIDCXBJDYXPTO-JAZONYGRSA-M 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
- 229940077388 benzenesulfonate Drugs 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 8
- 230000002093 peripheral effect Effects 0.000 claims description 8
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 8
- 239000003495 polar organic solvent Substances 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- JVKVEOKPRHZKNW-UHFFFAOYSA-N 2-hydroxybenzoic acid;hydrate Chemical compound O.OC(=O)C1=CC=CC=C1O JVKVEOKPRHZKNW-UHFFFAOYSA-N 0.000 claims description 6
- 208000005392 Spasm Diseases 0.000 claims description 6
- 150000008051 alkyl sulfates Chemical class 0.000 claims description 6
- 150000008052 alkyl sulfonates Chemical class 0.000 claims description 6
- 239000005557 antagonist Substances 0.000 claims description 6
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 claims description 6
- CTYRPMDGLDAWRQ-UHFFFAOYSA-N phenyl hydrogen sulfate Chemical compound OS(=O)(=O)OC1=CC=CC=C1 CTYRPMDGLDAWRQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 claims description 5
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 5
- 102000004895 Lipoproteins Human genes 0.000 claims description 5
- 108090001030 Lipoproteins Proteins 0.000 claims description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 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 5
- 229940049920 malate Drugs 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 230000023027 regulation of systemic arterial blood pressure by carotid body chemoreceptor signaling Effects 0.000 claims description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 5
- 206010002091 Anaesthesia Diseases 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 230000037005 anaesthesia Effects 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 230000007774 longterm Effects 0.000 claims description 4
- 150000002825 nitriles Chemical class 0.000 claims description 4
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 4
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical class 0.000 claims description 3
- 229940049964 oleate Drugs 0.000 claims description 3
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 3
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 2
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003586 protic polar solvent Substances 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 4
- DPKGTLUCCMJBQI-UHFFFAOYSA-N ethane-1,2-disulfonic acid;hydrate Chemical compound O.OS(=O)(=O)CCS(O)(=O)=O DPKGTLUCCMJBQI-UHFFFAOYSA-N 0.000 claims 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims 2
- 150000004683 dihydrates Chemical class 0.000 claims 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 150000008064 anhydrides Chemical class 0.000 claims 1
- 239000004568 cement Substances 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims 1
- 229940121647 egfr inhibitor Drugs 0.000 claims 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 229910052744 lithium Inorganic materials 0.000 claims 1
- YOIAWAIKYVEKMF-UHFFFAOYSA-N trifluoromethanesulfonic acid Chemical compound OS(=O)(=O)C(F)(F)F.OS(=O)(=O)C(F)(F)F YOIAWAIKYVEKMF-UHFFFAOYSA-N 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 311
- 239000000725 suspension Substances 0.000 description 107
- 239000000203 mixture Substances 0.000 description 89
- 239000000243 solution Substances 0.000 description 89
- 210000004027 cell Anatomy 0.000 description 47
- 238000001816 cooling Methods 0.000 description 36
- 238000001704 evaporation Methods 0.000 description 34
- 239000011550 stock solution Substances 0.000 description 34
- 239000002245 particle Substances 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- 238000009472 formulation Methods 0.000 description 28
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 28
- 239000003380 propellant Substances 0.000 description 28
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 238000003756 stirring Methods 0.000 description 27
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 26
- 239000004810 polytetrafluoroethylene Substances 0.000 description 26
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- 239000011148 porous material Substances 0.000 description 26
- 238000012360 testing method Methods 0.000 description 26
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- 238000002844 melting Methods 0.000 description 22
- 230000008018 melting Effects 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical group OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 20
- 239000012528 membrane Substances 0.000 description 20
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 20
- 238000003860 storage Methods 0.000 description 20
- 239000013543 active substance Substances 0.000 description 17
- 239000000443 aerosol Substances 0.000 description 17
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 16
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 16
- 239000002775 capsule Substances 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 15
- GVLGAFRNYJVHBC-UHFFFAOYSA-N hydrate;hydrobromide Chemical compound O.Br GVLGAFRNYJVHBC-UHFFFAOYSA-N 0.000 description 15
- 239000003921 oil Substances 0.000 description 14
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- 229910001961 silver nitrate Inorganic materials 0.000 description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 12
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 10
- 229960005070 ascorbic acid Drugs 0.000 description 10
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- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 9
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- 150000007513 acids Chemical class 0.000 description 9
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- 238000002156 mixing Methods 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 8
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
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- IHOXNOQMRZISPV-YJYMSZOUSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-methoxyphenyl)propan-2-yl]azaniumyl]ethyl]-2-oxo-1h-quinolin-8-olate Chemical compound C1=CC(OC)=CC=C1C[C@@H](C)NC[C@H](O)C1=CC=C(O)C2=C1C=CC(=O)N2 IHOXNOQMRZISPV-YJYMSZOUSA-N 0.000 description 6
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- 239000000600 sorbitol Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000004878 submucosal gland Anatomy 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- LPSWFOCTMJQJIS-UHFFFAOYSA-N sulfanium;hydroxide Chemical compound [OH-].[SH3+] LPSWFOCTMJQJIS-UHFFFAOYSA-N 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 229950007862 sulfonterol Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 239000006068 taste-masking agent Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 125000002640 tocopherol group Chemical class 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 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
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 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
-
- 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
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- 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
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Inorganic Compounds Of Heavy Metals (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05105270 | 2005-06-15 | ||
| PCT/EP2006/062688 WO2006134021A2 (en) | 2005-06-15 | 2006-05-30 | Process for preparing tiotropium salts, tiotropium salts as such and pharmaceutical compositions thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2007015997A true MX2007015997A (es) | 2008-03-07 |
Family
ID=35057150
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007015997A MX2007015997A (es) | 2005-06-15 | 2006-05-30 | Procedimiento para preparar nuevas sales de tiotropio, nuevas sales de tiotropio como tales y composiciones farmaceuticas de las mismas. |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US20060287530A1 (enExample) |
| EP (1) | EP1896026B1 (enExample) |
| JP (1) | JP5315048B2 (enExample) |
| KR (1) | KR20080024532A (enExample) |
| CN (1) | CN101227905A (enExample) |
| AR (1) | AR057067A1 (enExample) |
| AU (1) | AU2006259202B2 (enExample) |
| BR (1) | BRPI0611763A2 (enExample) |
| CA (1) | CA2611902C (enExample) |
| IL (1) | IL188069A0 (enExample) |
| MX (1) | MX2007015997A (enExample) |
| NZ (2) | NZ564697A (enExample) |
| RU (2) | RU2418796C2 (enExample) |
| TW (1) | TW200718698A (enExample) |
| WO (1) | WO2006134021A2 (enExample) |
| ZA (1) | ZA200709331B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2336126A1 (de) * | 2003-11-03 | 2011-06-22 | Boehringer Ingelheim International GmbH | Tiotropiumsalze, Verfahren zu deren Herstellung und Arzneimittelformulierungen diese enthaltend |
| JP5165245B2 (ja) * | 2003-11-03 | 2013-03-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規なチオトロピウム塩、その製造方法及びチオトロピウム塩を含有する医薬組成物 |
| DE102005035112A1 (de) * | 2005-07-27 | 2007-02-15 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neues Verfahren zur Herstellung von Tiotropiumsalzen unter Anwendung von in organischen Lösungsmitteln löslichen N-Methylscopiniumsalzen |
| WO2008101728A1 (de) * | 2007-02-23 | 2008-08-28 | K.H.S. Pharma Holding Gmbh | Verfahren zur herstellung von azoniaspironortropinestern und von nortropan-3-on verbindungen |
| GB0716026D0 (en) | 2007-08-16 | 2007-09-26 | Norton Healthcare Ltd | An inhalable medicament |
| WO2009031011A2 (en) * | 2007-09-05 | 2009-03-12 | Pfizer Limited | Xinafoate salt of n4-(2, 2-difluoro-4h-benz0 [1,4] 0xazin-3-one) -6-yl] -5-fluoro-n2- [3- (methylaminocar bonylmethyleneoxy) phenyl] 2, 4-pyrimidinediamine |
| PL388070A1 (pl) * | 2009-05-19 | 2010-11-22 | Adamed Spółka Z Ograniczoną Odpowiedzialnością | Nowe sole tiotropium |
| GB201200525D0 (en) | 2011-12-19 | 2012-02-29 | Teva Branded Pharmaceutical Prod R & D Inc | An inhalable medicament |
| CZ201241A3 (cs) | 2012-01-20 | 2013-07-31 | Zentiva, K.S. | Nové polymorfní formy tiotropium jodidu a zpusob jejich prípravy |
| US10034866B2 (en) | 2014-06-19 | 2018-07-31 | Teva Branded Pharmaceutical Products R&D, Inc. | Inhalable medicament comprising tiotropium |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3551492A (en) * | 1967-10-31 | 1970-12-29 | Ciba Geigy Corp | N,n'-diaminoalkoxy-benzyl-diamino-alkanes and the salts thereof |
| 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 |
| DE3546218A1 (de) * | 1985-12-27 | 1987-07-02 | Madaus & Co Dr | Azoniaspironortropanolester, verfahren zu deren herstellung und pharmazeutisches mittel |
| 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 |
| DE19528145A1 (de) * | 1995-08-01 | 1997-02-06 | Boehringer Ingelheim Kg | Neue Arzneimittel und ihre Verwendung |
| 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 |
| AU1499602A (en) * | 2000-10-12 | 2002-04-22 | Boehringer Ingelheim Pharma | Crystalline monohydrate, method for producing the same and the use thereof in the production of a medicament |
| IL149984A0 (en) * | 2000-10-12 | 2002-12-01 | Boehringer Ingelheim Pharma | Novel tiotropium-containing inhalation powder |
| US20020111363A1 (en) * | 2000-10-31 | 2002-08-15 | Karin Drechsel | Inhalable formulation of a solution containing a tiotropium salt |
| 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 |
| DE10111843A1 (de) * | 2001-03-13 | 2002-09-19 | Boehringer Ingelheim Pharma | Verbindungen zur Behandlung von inflammatorischen Erkrankungen |
| US20020193394A1 (en) * | 2001-03-13 | 2002-12-19 | Bernd Disse | Compounds for treating inflammatory diseases |
| 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 |
| 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 |
| US7311894B2 (en) * | 2002-03-28 | 2007-12-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | HFA suspension formulations containing an anticholinergic |
| WO2004064789A2 (en) * | 2003-01-16 | 2004-08-05 | University Of Rochester | Quaternary antimuscarinic compounds for the treatment of bladder diseases |
| JP5165245B2 (ja) * | 2003-11-03 | 2013-03-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規なチオトロピウム塩、その製造方法及びチオトロピウム塩を含有する医薬組成物 |
| EP2336126A1 (de) * | 2003-11-03 | 2011-06-22 | Boehringer Ingelheim International GmbH | Tiotropiumsalze, Verfahren zu deren Herstellung und Arzneimittelformulierungen diese enthaltend |
| 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
- 2006-05-30 AU AU2006259202A patent/AU2006259202B2/en not_active Ceased
- 2006-05-30 NZ NZ564697A patent/NZ564697A/en not_active IP Right Cessation
- 2006-05-30 EP EP06763345.3A patent/EP1896026B1/en active Active
- 2006-05-30 MX MX2007015997A patent/MX2007015997A/es not_active Application Discontinuation
- 2006-05-30 WO PCT/EP2006/062688 patent/WO2006134021A2/en not_active Ceased
- 2006-05-30 CN CNA2006800215844A patent/CN101227905A/zh active Pending
- 2006-05-30 JP JP2008516267A patent/JP5315048B2/ja active Active
- 2006-05-30 RU RU2007148256/04A patent/RU2418796C2/ru not_active IP Right Cessation
- 2006-05-30 CA CA2611902A patent/CA2611902C/en not_active Expired - Fee Related
- 2006-05-30 NZ NZ583872A patent/NZ583872A/en not_active IP Right Cessation
- 2006-05-30 KR KR1020087001206A patent/KR20080024532A/ko not_active Ceased
- 2006-05-30 BR BRPI0611763-5A patent/BRPI0611763A2/pt not_active IP Right Cessation
- 2006-06-14 TW TW095121214A patent/TW200718698A/zh unknown
- 2006-06-14 AR ARP060102507A patent/AR057067A1/es unknown
- 2006-06-15 US US11/424,244 patent/US20060287530A1/en not_active Abandoned
-
2007
- 2007-10-30 ZA ZA200709331A patent/ZA200709331B/xx unknown
- 2007-12-12 IL IL188069A patent/IL188069A0/en unknown
-
2010
- 2010-09-15 RU RU2010138174/04A patent/RU2010138174A/ru not_active Application Discontinuation
-
2014
- 2014-07-03 US US14/323,361 patent/US20140316138A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2006259202A1 (en) | 2006-12-21 |
| NZ583872A (en) | 2011-10-28 |
| TW200718698A (en) | 2007-05-16 |
| RU2010138174A (ru) | 2012-03-20 |
| CA2611902C (en) | 2013-08-27 |
| AU2006259202B2 (en) | 2012-05-10 |
| KR20080024532A (ko) | 2008-03-18 |
| WO2006134021A2 (en) | 2006-12-21 |
| RU2418796C2 (ru) | 2011-05-20 |
| WO2006134021A3 (en) | 2007-04-19 |
| US20140316138A1 (en) | 2014-10-23 |
| EP1896026A2 (en) | 2008-03-12 |
| NZ564697A (en) | 2010-04-30 |
| US20060287530A1 (en) | 2006-12-21 |
| JP2008543805A (ja) | 2008-12-04 |
| ZA200709331B (en) | 2008-10-29 |
| EP1896026B1 (en) | 2013-10-09 |
| IL188069A0 (en) | 2008-03-20 |
| AR057067A1 (es) | 2007-11-14 |
| RU2007148256A (ru) | 2009-07-20 |
| CN101227905A (zh) | 2008-07-23 |
| BRPI0611763A2 (pt) | 2010-09-28 |
| JP5315048B2 (ja) | 2013-10-16 |
| CA2611902A1 (en) | 2006-12-21 |
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| EP2093219A1 (de) | Kristalline, enantiomerenreine Salzform eines Betamimetikums und dessen Verwendung als Arzneimittel |
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