CA2534128A1 - Combination of an anticholinergic and a steroid and its use to treat respiratory disorders by inhalation - Google Patents

Combination of an anticholinergic and a steroid and its use to treat respiratory disorders by inhalation Download PDF

Info

Publication number
CA2534128A1
CA2534128A1 CA002534128A CA2534128A CA2534128A1 CA 2534128 A1 CA2534128 A1 CA 2534128A1 CA 002534128 A CA002534128 A CA 002534128A CA 2534128 A CA2534128 A CA 2534128A CA 2534128 A1 CA2534128 A1 CA 2534128A1
Authority
CA
Canada
Prior art keywords
alpha
beta
inhalable
composition according
propellant
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CA002534128A
Other languages
French (fr)
Other versions
CA2534128C (en
Inventor
Christopher John Montague Meade
Michel Pairet
Michael P. Pieper
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim International GmbH
Original Assignee
Individual
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34130038&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2534128(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Individual filed Critical Individual
Publication of CA2534128A1 publication Critical patent/CA2534128A1/en
Application granted granted Critical
Publication of CA2534128C publication Critical patent/CA2534128C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • 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
    • A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Abstract

The present invention relates to novel pharmaceutical compositions based on steroids and salts of an anticholinergic, processes for preparing them and their use in the treatment of respiratory complaints.

Claims (23)

1) Pharmaceutical compositions, characterised in that they contain one or more salts of formula 1 wherein X- denotes an anion with a single negative charge, preferably an anion selected from the group consisting of fluoride, chloride, bromide, iodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate, optionally in the form of the racemates, the enantiomers, and the hydrates thereof, combined with one or more steroids (2), optionally in the form of the enantiomers, mixtures of the enantiomers or in the form of the racemates thereof, optionally in the form of the solvates or hydrates and optionally together with a pharmaceutically acceptable excipient.
2) Pharmaceutical composition according to claim 1, characterised in that the active substances 1 and 2 are present either together in a single formulation or in two separate formulations.
3) Pharmaceutical composition according to claim 1 or 2, characterised in that the the compounds of formula 1 are present in form of the enantiomers of formula 1-en
4) Pharmaceutical composition according to one of claims 1 to 3, characterised in that the steroids 2 are selected from the group consisting of methyl prednisolone, prednisone, butixocort propionate, RPR-106541, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, ST-126, dexamethasone, 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-androsta-1,4-dime-17.beta.-carbothioic acid (S)-fluoromethyl ester, and 6.alpha.,9.alpha.-difluoro-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-17.alpha.-propionyloxy-androsta-1,4-dime-17.beta.-carbothioic acid (S)-(2-oxo-tetrahydro-furan-3S-yl) ester.
5) Pharmaceutical compositions according to one of claims 1 to 4, characterised in that the compounds 2 are present in the form of salts or derivatives including sodium salts, sulphobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates, palmitates, pivalates or furoates.
6) Pharmaceutical compositions according to one of claims 1 to 5, characterised in that the compounds 2 are selected from the group consisting of flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, ST-126, dexamethasone, 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-androsta-1,4-dime-17.beta.-carbothioic acid (S)-fluoromethyl ester, and 6.alpha.,9.alpha.-difluoro-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-17.alpha.-propionyloxy-androsta-1,4-dime-17.beta.-carbothioic acid (S)-(2-oxo-tetrahydro-furan-3S-yl) ester.
7) Pharmaceutical compositions according to one of claims 1 to 6, characterised in that the compounds 2 are selected from among budesonide, fluticasone, mometasone, ciclesonide, and 6.alpha.,9.alpha.-difluoro-17.alpha.-[(2-furanylcarbonyl)oxy]-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-androsta-1,4-dime-17.beta.-carbothioic acid (S)-fluoromethyl ester.
8) Pharmaceutical compositions according to one of claims 1 to 7, characterised in that the weight ratios of 1 to 2 are in a range from about 1;250 to 250:1, preferably from 1:150 to 150:1.
9) Pharmaceutical composition according to one of claims 1 to 8, characterised in that it is in the form of a preparation suitable for inhalation.
10) Pharmaceutical composition according to claim 9, characterised in that it is a preparation selected from among the inhalable powders, propellant-containing metered-dose aerosols and propellant-free inhalable solutions.
11) Pharmaceutical composition according to claim 10, characterised in that it is an inhalable powder which contains 1 and 2 in admixture with suitable physiologically acceptable excipients selected from among the monosaccharides, disaccharides, oligo- and polysaccharides, polyalcohols, salts, or mixtures of these excipients with one another.
12) Inhalable powder according to claim 11, characterised in that the excipient has a maximum average particle size of up to 250µm, preferably between 10 and 150µm.
13) Pharmaceutical composition according to claim 10, characterised in that it is an inhalable powder which contains only the active substances 1 and 2 as its ingredients.
14) Pharmaceutical composition according to claim 10, characterised in that it is a propellant-containing inhalable aerosol which contains 1 and 2 in dissolved or dispersed form.
15) Propellant-containing inhalable aerosol according to claim 14, characterised in that it contains, as propellant gas, hydrocarbons such as n-propane, n-butane or isobutane or halohydrocarbons such as chlorinated and/or fluorinated derivatives of methane, ethane, propane, butane, cyclopropane or cyclobutane.
16) Propellant-containing inhalable aerosol according to claim 15, characterised in that the propellant gas is TG11, TG12, TG134a, TG227 or mixtures thereof, preferably TG134a, TG227 or a mixture thereof.
17) Propellant-containing inhalable aerosol according to one of claims 14 to 16, characterised in that it may contain up to 5 % by weight of active substance 1 and/or 2.
18) Pharmaceutical composition according to claim 10, characterised in that it is a propellant-free inhalable solution which contains water, ethanol or a mixture of water and ethanol as solvent.
19) Inhalable solution according to claim 18, characterised in that it optionally contains other co-solvents and/or excipients.
20) Inhalable solution according to claim 19, characterised in that it contains as co-solvents ingredients which contain hydroxyl groups or other polar groups, e.g. alcohols - particularly isopropyl alcohol, glycols - particularly propyleneglycol, polyethyleneglycol, polypropyleneglycol, glycolether, glycerol, polyoxyethylene alcohols and polyoxyethylene fatty acid esters.
21) Inhalable solutions according to one of claims 19 or 20, characterised in that they contain as excipients surfactants, stabilisers, complexing agents, antioxidants and/or preservatives, flavourings, pharmacologically acceptable salts and/or vitamins.
22) Inhalable solutions according to claim 21, characterised in that they contain as complexing agents editic acid or a salt of editic acid, preferably sodium edetate.
23) Use of a composition according to one of claims 1 to 22 for preparing a medicament for the treatment of inflammatory or obstructive respiratory complaints, particularly asthma or COPD.
CA2534128A 2003-07-29 2004-07-17 Combination of an anticholinergic and a steroid and its use to treat respiratory disorders by inhalation Active CA2534128C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP03017162 2003-07-29
EP03017162.3 2003-07-29
PCT/EP2004/008029 WO2005014005A1 (en) 2003-07-29 2004-07-17 Combination of an anticholinergic and a steroid and its use to treat respiratory disorders by inhalation

Publications (2)

Publication Number Publication Date
CA2534128A1 true CA2534128A1 (en) 2005-02-17
CA2534128C CA2534128C (en) 2012-10-23

Family

ID=34130038

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2534128A Active CA2534128C (en) 2003-07-29 2004-07-17 Combination of an anticholinergic and a steroid and its use to treat respiratory disorders by inhalation

Country Status (12)

Country Link
EP (1) EP1651236A1 (en)
JP (1) JP2007500150A (en)
KR (1) KR20060052912A (en)
CN (1) CN1829520A (en)
AU (1) AU2004262901B2 (en)
BR (1) BRPI0413054A (en)
CA (1) CA2534128C (en)
IL (1) IL173370A0 (en)
MX (1) MXPA06001046A (en)
NZ (1) NZ545443A (en)
RU (1) RU2361586C2 (en)
WO (1) WO2005014005A1 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2165768B1 (en) 1999-07-14 2003-04-01 Almirall Prodesfarma Sa NEW DERIVATIVES OF QUINUCLIDINE AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM.
ES2298049B1 (en) 2006-07-21 2009-10-20 Laboratorios Almirall S.A. PROCEDURE FOR MANUFACTURING BROMIDE OF 3 (R) - (2-HIDROXI-2,2-DITIEN-2-ILACETOXI) -1- (3-PHENOXIPROPIL) -1-AZONIABICICLO (2.2.2) OCTANO.
EP2100598A1 (en) 2008-03-13 2009-09-16 Laboratorios Almirall, S.A. Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease
EP2100599A1 (en) 2008-03-13 2009-09-16 Laboratorios Almirall, S.A. Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease
EP2435023B1 (en) 2009-05-29 2016-07-06 Pearl Therapeutics, Inc. Compositions for pulmonary delivery of long-acting muscarinic antagonists and long-acting beta 2 adrenergic receptor agonists and associated methods and systems
US8815258B2 (en) 2009-05-29 2014-08-26 Pearl Therapeutics, Inc. Compositions, methods and systems for respiratory delivery of two or more active agents
EP2510928A1 (en) 2011-04-15 2012-10-17 Almirall, S.A. Aclidinium for use in improving the quality of sleep in respiratory patients
AU2014228414B2 (en) 2013-03-15 2018-09-13 Pearl Therapeutics, Inc. Methods and systems for conditioning of particulate crystalline materials

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2165768B1 (en) * 1999-07-14 2003-04-01 Almirall Prodesfarma Sa NEW DERIVATIVES OF QUINUCLIDINE AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM.
US20020183292A1 (en) * 2000-10-31 2002-12-05 Michel Pairet Pharmaceutical compositions based on anticholinergics and corticosteroids
ES2257152B1 (en) * 2004-05-31 2007-07-01 Laboratorios Almirall S.A. COMBINATIONS THAT INCLUDE ANTIMUSCARINIC AGENTS AND BETA-ADRENERGIC AGONISTS.

Also Published As

Publication number Publication date
KR20060052912A (en) 2006-05-19
EP1651236A1 (en) 2006-05-03
MXPA06001046A (en) 2006-04-24
IL173370A0 (en) 2006-06-11
JP2007500150A (en) 2007-01-11
NZ545443A (en) 2010-04-30
AU2004262901A1 (en) 2005-02-17
RU2006105719A (en) 2007-12-10
CA2534128C (en) 2012-10-23
AU2004262901B2 (en) 2010-05-13
RU2361586C2 (en) 2009-07-20
BRPI0413054A (en) 2006-10-17
CN1829520A (en) 2006-09-06
WO2005014005A1 (en) 2005-02-17

Similar Documents

Publication Publication Date Title
CA2481468A1 (en) Medicaments containing betamimetic drugs and a novel anticholinesterase drug
CA2455167A1 (en) New pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics
JP2007533683A5 (en)
CA2440699A1 (en) Compounds for treating inflammatory diseases
US3320125A (en) Inhalation aerosol composition
CA2439763A1 (en) Pharmaceutical compositions based on anticholinergics and pde-iv inhibitors
CA2733294C (en) Pharmaceutical combination of a tiotropium salt and ciclesonide
CA2427282A1 (en) Mixtures or organic compounds for the treatment of airway diseases
JP2006528228A (en) Salmeterol and ciclesonide combination
JP2016503390A (en) Pharmaceutical composition
CA2568834A1 (en) Medicaments for inhalation comprising steroids and an anticholinergic
CA2534120A1 (en) Medicaments for inhalation comprising anticholinergics and a betamimetic
WO2007042467A1 (en) Novel pharmaceutical combinations for the treatment of respiratory disorders
CA2481268A1 (en) Medicaments comprising steroids and a novel anticholinergic
CA2495454A1 (en) Pharmaceutical compositions for inhalation containing a new anticholinergic in conjunction with corticosteroids and betamimetics
CA2534128A1 (en) Combination of an anticholinergic and a steroid and its use to treat respiratory disorders by inhalation
US20030113268A1 (en) Degradation-resistant glucocorticosteroid formulations
JPS6247880B2 (en)
JP2007500676A5 (en)
JP2009500310A5 (en)
KR20100004993A (en) Stable pharmaceutical drug aerosols
CA2533792A1 (en) Medicaments for inhalation comprising steroids and fluorene carboxylic acid esters
JP2009537585A (en) Novel pharmaceutical composition for the treatment of respiratory diseases
CA2441964A1 (en) New pharmaceutical compositions based on anticholinergics and endothelin antagonists
US20030053957A1 (en) Degradation-resistant glucocorticosteroid formulations

Legal Events

Date Code Title Description
EEER Examination request