NO145199B - Analogifremgangsmaate for fremstilling av farmakologisk aktive nortropinestere - Google Patents
Analogifremgangsmaate for fremstilling av farmakologisk aktive nortropinestere Download PDFInfo
- Publication number
- NO145199B NO145199B NO763109A NO763109A NO145199B NO 145199 B NO145199 B NO 145199B NO 763109 A NO763109 A NO 763109A NO 763109 A NO763109 A NO 763109A NO 145199 B NO145199 B NO 145199B
- Authority
- NO
- Norway
- Prior art keywords
- preparation
- general formula
- pharmacologically active
- nortropinesters
- fluoroethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- YYMCYJLIYNNOMK-UHFFFAOYSA-N Nor-psi-tropine Chemical class C1C(O)CC2CCC1N2 YYMCYJLIYNNOMK-UHFFFAOYSA-N 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000013078 crystal Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- -1 benzylic acid nortropine esters Chemical class 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- GANYMSDHMBJFIL-UHFFFAOYSA-N acetonitrile;ethoxyethane Chemical compound CC#N.CCOCC GANYMSDHMBJFIL-UHFFFAOYSA-N 0.000 description 3
- UKXSKSHDVLQNKG-UHFFFAOYSA-N benzilic acid Chemical compound C=1C=CC=CC=1C(O)(C(=O)O)C1=CC=CC=C1 UKXSKSHDVLQNKG-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 125000001743 benzylic group Chemical group 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- YYMCYJLIYNNOMK-MEKDEQNOSA-N (1r,5s)-8-azabicyclo[3.2.1]octan-3-ol Chemical compound C1C(O)C[C@@H]2CC[C@H]1N2 YYMCYJLIYNNOMK-MEKDEQNOSA-N 0.000 description 1
- JTLAIKFGRHDNQM-UHFFFAOYSA-N 1-bromo-2-fluoroethane Chemical compound FCCBr JTLAIKFGRHDNQM-UHFFFAOYSA-N 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000005956 quaternization reaction Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000003756 stirring Methods 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
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
Denne oppfinnelse angår fremstilling av nye forbindelser med den generelle formel I
hvor R betyr en alkylgruppe med 1-4 karbonatomer og R<1> en p-fluoretylgruppe, og $ betyr et farmakologisk godtagbart anion, fortrinnsvis et halogenatom. De nye forbindelser med formel I fremstilles i henhold til oppfinnelsen ved omsetning av forbindelser med den generelle formel II med en forbindelse med den generelle formel III
hvor R og X har den ovenfor angitte betydning.
Kvarteriseringen kan utføres i et organisk, inert opp-løsningsmiddel så som acetonitril, toluen, kloroform eller aceton. Det egnede temperaturområde ligger mellom 0°C og reaksjons-blandingens koketemperatur.
Mellomproduktene med den generelle formel II kan fremstilles ved omsetning av benzilsyre-nortropinester med et alkyle-ringsmiddel med den generelle formel IV
hvor R' har den ovenfor angitte betydning, og Y er en reaktiv gruppe, f.eks. halogen.
Benzilsyre-nortropinesteren er kjent og kan fremstilles ved fremgangsmåten ifølge Pf leger e.a. Arzneim, Forsch. 1_7, 719
(1967).
De nye forbindelser med den generelle formel I er i be-sittelse av verdifulle farmakologiske egenskaper. Særlig virksom-me er de isomerer hvor R betyr en alkylgruppe, særlig en metyl-gruppe, og R' betyr særlig en |3-fluoretylgruppe. Forbindelsene er særlig godt egnet til behandling av spasmer og bronkialspasmer og for anvendelse ved forhøyet mavesekresjon. Som enkeltdose for oral anvendelse benyttes en mengde av aktivt stoff på 5-350 mg.
De følgende eksempler skal tjene til å illustrere oppfinnelsen ytterligere.
l-a) Benzilsyre- N- p- fluoretyl- nortropinester- hydroklorid
146,0 g (0,434 mol) benzilsyrenortropinester, 60,6 g
(0,477 mol) 2-bromfluoretan og 101,1 g (0,954 mol) natriumkarbonat oppvarmes under tilbakeløpskjøling og omrøring i 1200 ml acetonitril i 10 timer.
Efter avdestillering av acetonitrilet opptas det organisk-uorganiske residuum i vann og metylenklorid, og den alkaliske vann-fase ekstraheres flere ganger med metylenklorid.
De samlede metylenkloridfaser tørres over natriumsulfat.
Efter avsugning av natriumsulfatet fremstilles med hydrogen-klorid på vanlig måte benzilsyre-N-3-fluoretyl-nortropinester-hydrokloridet.
Utbytte: 131,3 g (91,2% av det teoretiske).
Hvite krystaller (metanol-eter), sm.p. 209°C (spaltn.). Elementæranalyse og spektra bekrefter at det er denne forbindelse som foreligger.
b) Benzilsyre- N- p- fluoretylnortropinester- metobromid
109,9 g (0,287 mol) benzilsyre-N-Ø-fluoretylnortropinester
(fremstilt fra hydrokloridet på vanlig måte) oppløses i en opp-løsningsmiddelblanding bestående av 4 50 ml absolutt metylenklorid og 300 ml absolutt acetonitril, og kvarteriseres med 136,1 g (1,433 mol) metylbromid ved romtemperatur.
Efter 3 dager avsuges krystallisatet, vaskes med aceton og tørres ved 50°C og et vakuum på 12 mm Hg.
Utbytte: 129,8 g (94,7% av det teoretiske).
Hvite krystaller (acetonitril), sm.p. 192-193°C (spaltn.). Elementæranalyse og spektra bekrefter at det er denne forbindelse som foreligger.
2. Benzilsyre- N- 3~ fluoretylnortropinester- etobromid
10,2 g (0,0266 mol) benzilsyre-N-3~fluoretylnortropinester (fremstilt på vanlig måte fra hydrokloridet) oppvarmes i 30 ml absolutt acetonitril under tilbakeløpskjøling under porsjonsvis til-setning av 23,2 g (0,213 mol) etylbromid. Fra oppløsningen utfelles litt efter litt hvite krystaller mens omsetningen skrider frem. Efter 14 dager avsuges de utfelte krystaller, vaskes med metylenklorid og tørres ved 50°C og et vakuum på 12 mm Hg.
Utbytte: 9,2 g (70,2% av det teoretiske).
Hvite krystaller (acetonitril-eter), sm.p. 215-216°C (spaltn.).
Elementæranalyse og spektra bekrefter at det er denne forbindelse som foreligger.
3. Benzilsyre- N- 3- fluoretyl- nortropinester- butobromid
6,7 g (0,0175 mol) benzilsyre-N-3-fluoretyl-nortropinester (fremstilt på vanlig måte fra hydrokloridet) oppvarmes i 20 ml absolutt acetonitril med 12,0 g (0,0875 mol) n-butylbromid under tilbakeløpskjøling. I løpet av en reaksjonsvarighet på 3 uker til-settes ytterligere 12,0 g (0,0875 mol) n-butylbromid. Efter av-sluttet omsetning avdestilleres oppløsningsmidlet, og residuet om-
krystalliseres fra acetonitril-eter.
Utbytte: 1,2 g (2 5,3% av det teoretiske)
Hvite krystaller (acetonitril-eter), sm.p. 201-202°C (spaltn.)
Elementæranalyse og spektra bekrefter at det er denne forbindelse som foreligger.
Claims (1)
- Analogifremgangsmåte for fremstilling av farmakologisk aktive nortropinestere med den generelle formel Ihvor R betyr en alkylgruppe med 1-4 karbonatomer og R<1> en 3-fluoretylgruppe, og X<®> betyr et farmakologisk godtagbart anion, fortrinnsvis halogen, karakterisert ved at en forbindelse med den generelle formel II hvor R' har den ovenfor angitte betydning, omsettes med en forbindelse med den generelle formel III hvor R og X har den ovenfor angitte betydning.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752540633 DE2540633A1 (de) | 1975-09-12 | 1975-09-12 | Neue quartaere n-beta-substituierte benzilsaeure-n-alkyl-nortropinester und verfahren zu deren herstellung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO763109L NO763109L (no) | 1977-03-15 |
| NO145199B true NO145199B (no) | 1981-10-26 |
| NO145199C NO145199C (no) | 1982-02-03 |
Family
ID=5956267
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO763109A NO145199C (no) | 1975-09-12 | 1976-09-10 | Analogifremgangsmaate for fremstilling av farmakologisk aktive nortropinestere. |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US4042700A (no) |
| JP (2) | JPS5236693A (no) |
| AT (1) | AT353428B (no) |
| AU (1) | AU506286B2 (no) |
| BE (1) | BE846104A (no) |
| CA (1) | CA1079733A (no) |
| CH (1) | CH621349A5 (no) |
| DE (1) | DE2540633A1 (no) |
| DK (1) | DK142988C (no) |
| ES (1) | ES451467A1 (no) |
| FI (1) | FI62083C (no) |
| FR (1) | FR2323387A1 (no) |
| GB (1) | GB1517086A (no) |
| IE (1) | IE44166B1 (no) |
| LU (1) | LU75781A1 (no) |
| MX (1) | MX4053E (no) |
| NL (1) | NL187210C (no) |
| NO (1) | NO145199C (no) |
| NZ (1) | NZ182011A (no) |
| PT (1) | PT65571B (no) |
| SE (1) | SE428472B (no) |
| ZA (1) | ZA765426B (no) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU174431B (hu) * | 1976-12-08 | 1980-01-28 | Egyt Gyogyszervegyeszeti Gyar | Sposob poluchenija novykh proizvodnykh nortropin-carbazata |
| DE3320138A1 (de) * | 1983-06-03 | 1984-12-06 | Boehringer Ingelheim KG, 6507 Ingelheim | Neues nortropinderivat, verfahren zu seiner herstellung und seine verwendung |
| DE4108393A1 (de) * | 1991-03-15 | 1992-09-17 | Boehringer Ingelheim Kg | Neue ester bi- und tricyclischer aminoalkohole, ihre herstellung und ihre verwendung in arzneimitteln |
| JPH0558911A (ja) * | 1991-08-27 | 1993-03-09 | N D Shinyaku Kaihatsu Kenkyusho:Kk | 鎮咳去痰剤 |
| 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 |
| SK15382002A3 (sk) * | 2000-04-27 | 2003-03-04 | Boehringer Ingelheim Pharma Kg | Betamimetiká, farmaceutický prostriedok s ich obsahom a ich použitie |
| IL149984A0 (en) * | 2000-10-12 | 2002-12-01 | Boehringer Ingelheim Pharma | Novel tiotropium-containing inhalation powder |
| 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 |
| DE10050995A1 (de) * | 2000-10-14 | 2002-04-18 | Boehringer Ingelheim Pharma | Neue Anticholinergika, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| US20020111363A1 (en) * | 2000-10-31 | 2002-08-15 | 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 |
| 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 |
| US20020151541A1 (en) * | 2000-10-31 | 2002-10-17 | Michel Pairet | Pharmaceutical compositions containing tiotropium salts and antihistamines and their use |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| EP1494648B1 (en) * | 2002-04-04 | 2006-09-20 | Boehringer Ingelheim Pharma GmbH & Co.KG | Powder formulations suitable for inhalation |
| US20030235538A1 (en) * | 2002-04-09 | 2003-12-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Method for the administration of an anticholinergic by inhalation |
| DE10216427A1 (de) * | 2002-04-12 | 2003-10-23 | Boehringer Ingelheim Pharma | Arzneimittelkompositionen enthaltend heterocyclische Verbindungen und ein neues Anticholinergikum |
| US7417051B2 (en) * | 2002-04-12 | 2008-08-26 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Medicaments comprising betamimetics and a novel anticholinergic |
| US7084153B2 (en) * | 2002-04-12 | 2006-08-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Medicaments comprising steroids and a novel anticholinergic |
| US7094788B2 (en) * | 2002-04-13 | 2006-08-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Esters of hydroxyl-substituted nitrogen heterocycles, processes for the preparation thereof as well as the use thereof as pharmaceutical compositions |
| 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 |
| USD831375S1 (en) | 2017-01-20 | 2018-10-23 | The Gillette Company Llc | Shaving razor stand |
| EP3351138B1 (en) | 2017-01-20 | 2020-09-09 | The Gillette Company LLC | Personal care product docking system |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3505337A (en) * | 1967-12-22 | 1970-04-07 | Boehringer Sohn Ingelheim | N - hydrocarbyl-substituted noratropinium,haloalkylates and o-acyl derivatives thereof |
-
1975
- 1975-09-12 DE DE19752540633 patent/DE2540633A1/de active Granted
-
1976
- 1976-08-20 AT AT618676A patent/AT353428B/de not_active IP Right Cessation
- 1976-09-03 US US05/720,245 patent/US4042700A/en not_active Expired - Lifetime
- 1976-09-09 FR FR7627151A patent/FR2323387A1/fr active Granted
- 1976-09-09 FI FI762590A patent/FI62083C/fi not_active IP Right Cessation
- 1976-09-09 GB GB37447/76A patent/GB1517086A/en not_active Expired
- 1976-09-09 CH CH1145576A patent/CH621349A5/de not_active IP Right Cessation
- 1976-09-10 PT PT65571A patent/PT65571B/pt unknown
- 1976-09-10 NO NO763109A patent/NO145199C/no unknown
- 1976-09-10 NZ NZ182011A patent/NZ182011A/xx unknown
- 1976-09-10 NL NLAANVRAGE7610063,A patent/NL187210C/xx not_active IP Right Cessation
- 1976-09-10 IE IE2032/76A patent/IE44166B1/en not_active IP Right Cessation
- 1976-09-10 BE BE170555A patent/BE846104A/xx not_active IP Right Cessation
- 1976-09-10 SE SE7610070A patent/SE428472B/xx not_active IP Right Cessation
- 1976-09-10 MX MX764898U patent/MX4053E/es unknown
- 1976-09-10 LU LU75781A patent/LU75781A1/xx unknown
- 1976-09-10 DK DK411576A patent/DK142988C/da active
- 1976-09-10 AU AU17629/76A patent/AU506286B2/en not_active Expired
- 1976-09-10 ZA ZA00765426A patent/ZA765426B/xx unknown
- 1976-09-10 JP JP51108667A patent/JPS5236693A/ja active Granted
- 1976-09-11 ES ES451467A patent/ES451467A1/es not_active Expired
- 1976-09-13 CA CA261,037A patent/CA1079733A/en not_active Expired
-
1986
- 1986-06-18 JP JP61142449A patent/JPS625983A/ja active Granted
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