IL159238A - Crystalline anticholinergic, method for its production and use thereof in the production of a drug - Google Patents

Crystalline anticholinergic, method for its production and use thereof in the production of a drug

Info

Publication number
IL159238A
IL159238A IL159238A IL15923803A IL159238A IL 159238 A IL159238 A IL 159238A IL 159238 A IL159238 A IL 159238A IL 15923803 A IL15923803 A IL 15923803A IL 159238 A IL159238 A IL 159238A
Authority
IL
Israel
Prior art keywords
tiotropium bromide
crystalline
anhydrous
production
pharmaceutical composition
Prior art date
Application number
IL159238A
Original Assignee
Boehringer Ingelheim Pharma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boehringer Ingelheim Pharma filed Critical Boehringer Ingelheim Pharma
Publication of IL159238A publication Critical patent/IL159238A/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D451/00Heterocyclic 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
    • C07D451/02Heterocyclic 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
    • C07D451/04Heterocyclic 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
    • C07D451/06Oxygen atoms
    • C07D451/10Oxygen atoms acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/468-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics

Abstract

The invention relates to crystalline, water-free (1 alpha ,2 beta ,4 beta ,5 alpha ,7 beta )-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0<2,4>]nonane-bromide, to a method for its production, and to the use thereof in the production of a drug, especially in the production of an anticholinergic drug. [WO03000265A1]

Claims (10)

1. 59238/2 19 78190amd.209^r Amended claims V 1 ) Anhydrous crystalline tiotropium bromide, characterised by a monoclinic elementary cell with the parameters a = 10.4336(2)A, b = 11 .3297(3)A, c = 17.6332(4) A, a = 90°, β = 105.158(2)° and λ = 90° (cell volume=201 1.89(8) A3) determined by X-ray structural analysis.
2. ) Process for preparing crystalline, anhydrous tiotropium bromide according to claim 1, characterized in that it is prepared by careful drying of monohydrate tiotropium bromide at more than 50°C, preferably at 60-100°C, under reduced pressure.
3. ) Process according to claim 2, characterised in that the drying is carried out over a period of from 15 minutes to 24 hours.
4. ) Process for preparing crystalline, anhydrous tiotropium bromide, according to claim 1 , characterised in that it is prepared by storing crystalline tiotropium bromide monohydrate over a suitable drying agent for a period of 12 to 96 hours.
5. ) Crystalline anhydrous tiotropium bromide, obtainable according to one of claims 2, 3 or 4.
6. ) Pharmaceutical composition, characterised in that it contains crystalline anhydrous tiotropium bromide according to one of claims 1 or 5.
7. ) Pharmaceutical composition according to claim 6, characterised in that it is an inhalable powder.
8. ) Inhalable powder according to claim 7, characterised in that it contains crystalline anhydrous tiotropium bromide according to claim 1 or 5 in admixture with a physiologically acceptable excipient.
9. ) Inhalable powder according to claim 8, characterised in that the excipient is selected from the group consisting of glucose and lactose.
10. ) Use of crystalline anhydrous tiotropium bromide according to one of claims 1 or 5 for preparing a pharmaceutical composition for the treatment of diseases in which the administration of an anticholinergic may have a therapeutic benefit. 1 Use according to claim 10, characterised in that the diseases are asthma or COPD. For th© Applicants MOID COHM AND PABINBS
IL159238A 2001-06-22 2003-12-08 Crystalline anticholinergic, method for its production and use thereof in the production of a drug IL159238A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10129710 2001-06-22
DE10215436 2002-04-08
PCT/EP2002/006291 WO2003000265A1 (en) 2001-06-22 2002-06-08 Crystalline anticholinergic, method for its production, and use thereof in the production of a drug

Publications (1)

Publication Number Publication Date
IL159238A true IL159238A (en) 2010-04-15

Family

ID=26009556

Family Applications (2)

Application Number Title Priority Date Filing Date
IL15923802A IL159238A0 (en) 2001-06-22 2002-06-08 Crystalline anticholinergic, method for its production, and use thereof in the production of a drug
IL159238A IL159238A (en) 2001-06-22 2003-12-08 Crystalline anticholinergic, method for its production and use thereof in the production of a drug

Family Applications Before (1)

Application Number Title Priority Date Filing Date
IL15923802A IL159238A0 (en) 2001-06-22 2002-06-08 Crystalline anticholinergic, method for its production, and use thereof in the production of a drug

Country Status (38)

Country Link
EP (1) EP1401445B1 (en)
JP (1) JP2005504015A (en)
KR (2) KR100971616B1 (en)
CN (1) CN100586948C (en)
AR (1) AR037491A1 (en)
AT (1) ATE337006T1 (en)
AU (1) AU2002345016B2 (en)
BG (1) BG66303B1 (en)
BR (1) BR0210537A (en)
CA (1) CA2450961C (en)
CO (1) CO5550423A2 (en)
CY (1) CY1105223T1 (en)
CZ (1) CZ302786B6 (en)
DE (1) DE50207943D1 (en)
DK (1) DK1401445T3 (en)
EA (1) EA005813B1 (en)
EE (1) EE05316B1 (en)
EG (1) EG24851A (en)
ES (1) ES2271280T3 (en)
HK (1) HK1068540A1 (en)
HR (1) HRP20031066B1 (en)
HU (1) HUP0400333A3 (en)
IL (2) IL159238A0 (en)
ME (1) ME00412B (en)
MX (1) MXPA03011718A (en)
MY (1) MY122779A (en)
NO (1) NO334301B1 (en)
NZ (1) NZ530690A (en)
PE (2) PE20030130A1 (en)
PL (1) PL208137B1 (en)
PT (1) PT1401445E (en)
RS (1) RS50441B (en)
SA (1) SA02230255B1 (en)
SI (1) SI1401445T1 (en)
SK (1) SK287262B6 (en)
TW (2) TWI261589B (en)
UY (1) UY27342A1 (en)
WO (1) WO2003000265A1 (en)

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Also Published As

Publication number Publication date
CN100586948C (en) 2010-02-03
BG66303B1 (en) 2013-03-29
PT1401445E (en) 2006-10-31
EP1401445B1 (en) 2006-08-23
MY122779A (en) 2006-05-31
AU2002345016B2 (en) 2008-04-17
NZ530690A (en) 2005-05-27
CO5550423A2 (en) 2005-08-31
JP2005504015A (en) 2005-02-10
ME00412B (en) 2011-10-10
CZ2004120A3 (en) 2004-05-12
DK1401445T3 (en) 2006-11-27
EA005813B1 (en) 2005-06-30
AR037491A1 (en) 2004-11-17
PL364489A1 (en) 2004-12-13
SI1401445T1 (en) 2007-02-28
YU99703A (en) 2006-05-25
DE50207943D1 (en) 2006-10-05
EP1401445A1 (en) 2004-03-31
CY1105223T1 (en) 2010-03-03
CA2450961A1 (en) 2003-01-03
MEP62008A (en) 2011-05-10
HK1068540A1 (en) 2005-04-29
KR20090031638A (en) 2009-03-26
HRP20031066B1 (en) 2011-10-31
PL208137B1 (en) 2011-03-31
HUP0400333A2 (en) 2004-12-28
TWI261589B (en) 2006-09-11
NO20035696D0 (en) 2003-12-19
WO2003000265A1 (en) 2003-01-03
SK522004A3 (en) 2004-06-08
EE200400029A (en) 2004-04-15
PE20081305A1 (en) 2008-10-01
BG108440A (en) 2004-08-31
SK287262B6 (en) 2010-04-07
KR101011353B1 (en) 2011-01-28
EG24851A (en) 2010-10-27
KR20040018285A (en) 2004-03-02
CZ302786B6 (en) 2011-11-09
MXPA03011718A (en) 2004-12-06
CN1520294A (en) 2004-08-11
EE05316B1 (en) 2010-08-16
ATE337006T1 (en) 2006-09-15
NO334301B1 (en) 2014-02-03
BR0210537A (en) 2004-06-22
RS50441B (en) 2010-03-02
CA2450961C (en) 2010-03-30
TW200617007A (en) 2006-06-01
KR100971616B1 (en) 2010-07-22
EA200301293A1 (en) 2004-08-26
SA02230255B1 (en) 2006-10-31
HUP0400333A3 (en) 2012-10-29
UY27342A1 (en) 2003-02-28
HRP20031066A2 (en) 2004-04-30
ES2271280T3 (en) 2007-04-16
IL159238A0 (en) 2004-06-01
PE20030130A1 (en) 2003-04-02

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