NO159172B - Nye n-alkyl-norskopiner. - Google Patents
Nye n-alkyl-norskopiner. Download PDFInfo
- Publication number
- NO159172B NO159172B NO831447A NO831447A NO159172B NO 159172 B NO159172 B NO 159172B NO 831447 A NO831447 A NO 831447A NO 831447 A NO831447 A NO 831447A NO 159172 B NO159172 B NO 159172B
- Authority
- NO
- Norway
- Prior art keywords
- general formula
- alkyl
- new
- ethanol
- norscopins
- Prior art date
Links
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009466 transformation Effects 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
-
- 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
- A61P11/08—Bronchodilators
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Mushroom Cultivation (AREA)
- Preparation Of Fruits And Vegetables (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Saccharide Compounds (AREA)
Description
Denne oppfinnelse angår nye N-alkyl-norskopiner med den generelle formel
hvor R er en lineær eller forgrenet alkylrest med 2-10 karbon-åtomer. N-alkyl-norskopinene med den generelle formel I er verdifulle mellomprodukter, f.eks. for fremstilling av nye dibenzo-[b,e]tiepin-ll-N-alkyl-norskopinetere med den generelle formel II
hvor R er en lineær eller forgrenet alkylrest med 2-10 karbon-atomer, og x' ^ er et farmakologisk godtagbart anion så som et halogenatom eller resten av en organisk sulfonsyre.
Disse forbindelser er på sin side verdifulle farmasøytika med et godt avpasset forhold mellom anticholinerg og anti-histaminisk virkning. De egner seg derfor meget godt til be-handling av spasmer og obstruktive luftveislidelser. Disse forbindelser er nærmere beskrevet i patentansøkning 83.1084.
Viderebearbeidelsen av forbindelsene med den generelle formel I til N-alkylnorskopinetrene med den ovenstående generelle formel II kan skje ved at man omsetter dem med forbindelser med den generelle formel III
hvor X er en lett avspaltbar gruppe (f.eks. et halogenatom), til tertiære forbindelser med den generelle formel IV hvor R har den ovenfor angitte betydning, og sistnevnte over-føres til de kvartære salter med den generelle formel II med vanlige metyleringsmidler med den generelle formel
hvor X har den ovenfor angitte betydning.
Med hensyn til nærmere detaljer vedrørende viderebearbeidelsen av N-alkylnorskopinene med den generelle formel I henvises til ovennevnte patentansøkning 83.1084.
Forbindelsene med den generelle formel I fremstilles ved at N-alkylnorskopolaminer med den generelle formel VI
resp. salter derav behandles med egnede komplekse metall-hydrider (fortrinnsvis ved romtemperatur eller lavere temperaturer) i et oppløsningsmiddel. Særlig egnet er metallborhydrider og spesielt natriumborhydrid (NaBH^). Også litiumalanat er prinsipielt egnet, men for å unngå bireaksjoner bør man anvende temperaturer på 0°C og lavere.
Som oppløsningsmiddel for den ovenfor angitte omsetning kommer først og fremst etanol i betraktning. Høyere alkoholer og andre organiske oppløsningsmidler (f.eks. etere) er mindre gunstige, da de fortrinnsvis som utgangsmateriale anvendte salter av forbindelsene med den generelle formel VI er tungt-løselige i dem. Også metanol er mindre egnet, da det f.eks. spalter meget raskt natriumborhydrid allerede ved 0°C, slik at den anvendte mengde av dette stoff blir unødvendig stor. Også
i vann kan hydrogenolysen av forbindelsene med formel VI gjennom-føres når f.eks. en pH på 6-7 anvendes. Den påfølgende isolering av N-alkylnorskopiner fra vann er imidlertid mer brysom enn fra etanol.
Fremstillingen av de som utgangsmaterialer anvendte N-alkylnorskopolaminer med den generelle formel VI er beskrevet 1 DE-AS 1 670 048.
De følgende eksempler illustrerer oppfinnelsen ytterligere.
Eksempel 1
N- isopropylnorskopin og dets hydroklorid
36,8 g (0,1 mol) N-isopropylnorskopolamin-hydroklorid suspenderes i 370 ml etanol, og ved en temperatur på 20°C
under stadig omrøring tilsettes 3,78 g (0,1 mol) natriumbor-
hydrid i seks porsjoner med 15 minutters mellomrom. Man lar det hele efterreagere i 12 timer. Hydrogenolysen er efter denne tid avsluttet. Ved -5 til -10°C innføres nu under nitrogenatmosfære hydrogenkloridgass til sur reaksjon, og oppløsningen vaskes fri for hydrogenklorid med 1,5 liter eter.
De efter tørring fint utgnidde krystaller suspenderer man i
2 liter metylenklorid, oppvarmer til kokning og innfører ammoniakk i det kokende metylenklorid til fullstendig omsetning for å danne basen. Efter fraskillelse av de organiske salter avdestilleres metylenklorid under redusert trykk ved 30°C.
Farveløse krystaller (cykloheksan), smeltepunkt 118-119,5°C. Utbytte: 15,8 g (86,2% av det teoretiske).
Hydrokloridet kan fremstilles på vanlig måte.
Farveløse krystaller (etanol), smeltepunkt 255°C (dekomp.), (omvandlingspunkt ~230°C).
Ved elementæranalyse og spektra bekreftes tilstedeværelse
av denne forbindelse.
Eksempel 2
N- etylnorskopin- hydroklorid
35,4 g (0,1 mol) N-etylnorskopolamin-hydroklorid suspenderes
i 350 ml etanol, og ved en temperatur på 20°C tilsettes 3,78 g = 0,1 mol natriumborhydrid under stadig omrøring i seks porsjoner med 20 minutters mellomrom. Derefter går man frem som i eksempel 1. Fra den etanoliske oppløsning får man ved overmetning med eter farveløse krystaller (etanol/eter) med smeltepunkt 139-141°C (dekomp.).
Eksempel 3
N- n- propylnorskopin- hydroklorid
Fra 36,8 g (0,1 mol) N-n-propylnorskopolamin fremstilles ved hjelp av 3,78 g (= 0,1 mol) natriumborhydrid i etanol analogt med fremgangsmåten i eksempel 1 den i tittelen angitte forbindelse.
Farveløse krystaller (fra etanol/eter) med smeltepunkt 241-241,5°C (dekomp.).
Eksempel 4
N- n- butylnorskopin- hydroklorid
Fra 38,2 g (0,1 mol) N-n-butylnorskopolamin fremstilles ved hjelp av 3,78 g (0,1 mol) natriumborhydrid i etanol analogt med fremgangsmåten i eksempel 1 den i tittelen angitte forbindelse.
Farveløse krystaller (fra acetonitril) med smeltepunkt 198°C.
Claims (1)
1. Nye N-alkyl-norskopiner, karakterisert ved den generelle formel
hvor R er en lineær eller forgrenet alkylrest med 2-10 karbon-atomer, og syreaddisjonssalter derav.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19823215493 DE3215493A1 (de) | 1982-04-26 | 1982-04-26 | Neue zwischenprodukte, verfahren zu ihrer herstellung und ihre verwendung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO831447L NO831447L (no) | 1983-10-27 |
| NO159172B true NO159172B (no) | 1988-08-29 |
| NO159172C NO159172C (no) | 1988-12-07 |
Family
ID=6161961
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO831447A NO159172C (no) | 1982-04-26 | 1983-04-25 | Nye n-alkyl-norskopiner. |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US4783534A (no) |
| EP (1) | EP0092814B1 (no) |
| JP (1) | JPS58201779A (no) |
| KR (1) | KR900004127B1 (no) |
| AT (1) | ATE16185T1 (no) |
| AU (1) | AU557680B2 (no) |
| CA (1) | CA1254566A (no) |
| CS (1) | CS236873B2 (no) |
| DD (1) | DD211114A5 (no) |
| DE (2) | DE3215493A1 (no) |
| DK (1) | DK159777C (no) |
| ES (1) | ES521809A0 (no) |
| FI (1) | FI831234L (no) |
| GR (1) | GR78837B (no) |
| HU (1) | HU193161B (no) |
| IE (1) | IE55308B1 (no) |
| IL (1) | IL68479A0 (no) |
| NO (1) | NO159172C (no) |
| NZ (1) | NZ203980A (no) |
| PH (1) | PH23301A (no) |
| PL (1) | PL138718B1 (no) |
| PT (1) | PT76584B (no) |
| YU (1) | YU43731B (no) |
| ZA (1) | ZA832883B (no) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4021847C2 (de) * | 1990-07-09 | 1994-09-08 | Stockhausen Chem Fab Gmbh | Verfahren zur Herstellung wasserquellbarer Produkte unter Verwendung von Feinstanteilen wasserquellbarer Polymerer |
| IL152140A0 (en) * | 2000-04-27 | 2003-05-29 | Boehringer Ingelheim Pharma | Novel, slow-acting betamimetics, a method for their production and their use as medicaments |
| WO2002030389A1 (de) * | 2000-10-12 | 2002-04-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue tiotropium-haltige inhalationspulver |
| US6908928B2 (en) | 2000-10-12 | 2005-06-21 | Bi Pharma Kg. | Crystalline tiotropium bromide monohydrate, processes for the preparation thereof, and pharmaceutical compositions |
| US6706726B2 (en) * | 2000-10-14 | 2004-03-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Anticholinergics which may be used as medicaments as well as processes for preparing them |
| US6852728B2 (en) | 2000-10-14 | 2005-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Anticholinergics, processes for preparing them, and pharmaceutical compositions containing them |
| US20020151541A1 (en) * | 2000-10-31 | 2002-10-17 | Michel Pairet | Pharmaceutical compositions containing tiotropium salts and antihistamines and their use |
| DE10062712A1 (de) * | 2000-12-15 | 2002-06-20 | Boehringer Ingelheim Pharma | Neue Arzneimittelkompositionen auf der Basis von Anticholinergika und Corticosteroiden |
| US20020137764A1 (en) * | 2000-10-31 | 2002-09-26 | Karin Drechsel | Inhalable formulation of a solution containing a tiotropium salt |
| US7776315B2 (en) * | 2000-10-31 | 2010-08-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and additional active ingredients |
| 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 |
| US20100310477A1 (en) * | 2000-11-28 | 2010-12-09 | Boehringer Ingelheim Pharma Gmbh & Co. Kg. | Pharmaceutical compositions based on anticholingerics and additional active ingredients |
| US20030013675A1 (en) * | 2001-05-25 | 2003-01-16 | Boehringer Ingelheim Pharma Kg | Combination of an adenosine A2A-receptor agonist and tiotropium or a derivative thereof for treating obstructive airways and other inflammatory diseases |
| US20030070679A1 (en) * | 2001-06-01 | 2003-04-17 | Boehringer Ingelheim Pharma Kg | Capsules containing inhalable tiotropium |
| US20030018019A1 (en) * | 2001-06-23 | 2003-01-23 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics |
| DE10141377A1 (de) * | 2001-08-23 | 2003-03-13 | Boehringer Ingelheim Pharma | Aufstreuverfahren zur Herstellung von Pulverformulierungen |
| US6919325B2 (en) * | 2001-09-14 | 2005-07-19 | Boehringer Ingelheim Pharma Kg | Pharmaceutical compositions containing tiotropium salts and low-solubility salmeterol salts |
| DE10200943A1 (de) | 2002-01-12 | 2003-07-24 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Scopinestern |
| US6790856B2 (en) | 2002-01-31 | 2004-09-14 | Boehringer Ingelheim Pharma Kg | Fluorenecarboxylic acid esters, process for the manufacture thereof, and use thereof as medicaments |
| US7405224B2 (en) * | 2002-01-31 | 2008-07-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthenecarboxylates, processes for preparing them, and their use 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 |
| 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 |
| DK1494648T3 (da) * | 2002-04-04 | 2006-12-27 | Boehringer Ingelheim Pharma | Pulverpræparat til inhalation |
| US20030235538A1 (en) * | 2002-04-09 | 2003-12-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Method for the administration of an anticholinergic by inhalation |
| US7084153B2 (en) * | 2002-04-12 | 2006-08-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Medicaments comprising steroids and a novel anticholinergic |
| US7417051B2 (en) * | 2002-04-12 | 2008-08-26 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Medicaments comprising betamimetics and a novel anticholinergic |
| US7763280B2 (en) * | 2002-11-28 | 2010-07-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Tiotropium containing powder formulation for inhalation |
| DE10345065A1 (de) * | 2003-09-26 | 2005-04-14 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Aerosolformulierung für die Inhalation enthaltend ein Anticholinergikum |
| SE0303570L (sv) * | 2003-12-03 | 2005-06-04 | Microdrug Ag | Fukt-känslig medicinsk produkt |
| TWI274641B (en) * | 2005-08-30 | 2007-03-01 | Rexon Ind Corp Ltd | Cutting machine |
| CN115572291A (zh) * | 2022-09-28 | 2023-01-06 | 成都第一制药有限公司 | 一种氢溴酸山莨菪碱及其制备方法和质量控制方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3211185A1 (de) * | 1982-03-26 | 1983-09-29 | Boehringer Ingelheim KG, 6507 Ingelheim | Neue quartaere 6,11-dihydro-dibenzo-(b,e)-thiepin-11-n-alkyl- norscopinether und verfahren zu deren herstellung |
-
1982
- 1982-04-26 DE DE19823215493 patent/DE3215493A1/de not_active Withdrawn
-
1983
- 1983-04-13 FI FI831234A patent/FI831234L/fi not_active Application Discontinuation
- 1983-04-20 DD DD83250031A patent/DD211114A5/de not_active IP Right Cessation
- 1983-04-21 GR GR71157A patent/GR78837B/el unknown
- 1983-04-21 PT PT76584A patent/PT76584B/pt not_active IP Right Cessation
- 1983-04-22 EP EP83103935A patent/EP0092814B1/de not_active Expired
- 1983-04-22 NZ NZ203980A patent/NZ203980A/en unknown
- 1983-04-22 AT AT83103935T patent/ATE16185T1/de not_active IP Right Cessation
- 1983-04-22 DE DE8383103935T patent/DE3361054D1/de not_active Expired
- 1983-04-25 IL IL68479A patent/IL68479A0/xx not_active IP Right Cessation
- 1983-04-25 NO NO831447A patent/NO159172C/no unknown
- 1983-04-25 DK DK182583A patent/DK159777C/da active
- 1983-04-25 KR KR1019830001742A patent/KR900004127B1/ko not_active IP Right Cessation
- 1983-04-25 YU YU939/83A patent/YU43731B/xx unknown
- 1983-04-25 ZA ZA832883A patent/ZA832883B/xx unknown
- 1983-04-25 IE IE938/83A patent/IE55308B1/en not_active IP Right Cessation
- 1983-04-25 JP JP58072766A patent/JPS58201779A/ja active Granted
- 1983-04-25 HU HU831415A patent/HU193161B/hu not_active IP Right Cessation
- 1983-04-25 CS CS832919A patent/CS236873B2/cs unknown
- 1983-04-25 ES ES521809A patent/ES521809A0/es active Granted
- 1983-04-25 PL PL1983241635A patent/PL138718B1/pl unknown
- 1983-04-25 CA CA000426597A patent/CA1254566A/en not_active Expired
- 1983-04-26 AU AU13945/83A patent/AU557680B2/en not_active Ceased
-
1984
- 1984-08-13 PH PH31101A patent/PH23301A/en unknown
-
1987
- 1987-03-31 US US07/032,762 patent/US4783534A/en not_active Expired - Fee Related
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