CA2441964A1 - New pharmaceutical compositions based on anticholinergics and endothelin antagonists - Google Patents

New pharmaceutical compositions based on anticholinergics and endothelin antagonists Download PDF

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Publication number
CA2441964A1
CA2441964A1 CA002441964A CA2441964A CA2441964A1 CA 2441964 A1 CA2441964 A1 CA 2441964A1 CA 002441964 A CA002441964 A CA 002441964A CA 2441964 A CA2441964 A CA 2441964A CA 2441964 A1 CA2441964 A1 CA 2441964A1
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CA
Canada
Prior art keywords
inhalable
acid
pharmaceutical composition
composition according
propellant
Prior art date
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Granted
Application number
CA002441964A
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French (fr)
Other versions
CA2441964C (en
Inventor
Michel Pairet
Michael Paul Pieper
Christopher John Montague Meade
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Boehringer Ingelheim Pharma GmbH and Co KG
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Individual
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Publication of CA2441964A1 publication Critical patent/CA2441964A1/en
Application granted granted Critical
Publication of CA2441964C publication Critical patent/CA2441964C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • 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
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • 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
    • 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
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • 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
    • 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
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions

Abstract

The invention relates to novel medicament compositions based on anticholinergic agents and endothelin antagonists, to a method for their production and to the use thereof for treating diseases of the respiratory tract.

Claims (35)

1) Pharmaceutical compositions characterised in that they contain one or more anticholinergics (1) combined with one or more endothelin antagonists (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 one of claims 1 and 2, characterised in that 1 is selected from among tiotropium salts, oxitropium salts or ipratropium salts.
4) Pharmaceutical composition according to one of claims 1 to 3, characterised in that 1 is present in the form of the chloride, bromide, iodide, methanesulphonate or paratoluene sulphonate, preferably in the form of the bromide.
5) Pharmaceutical composition according to one of claims 1 to 4, characterised in that 2 is selected from among tezosentan, bosentan, enrasentan, sixtasentan, T-0201, BMS-193884, K-8794, PD-156123, PD-156707, PD-160874, PD-180988, S-0139 and ZD-1611.
6) Pharmaceutical composition according to one of claims 1 to 5, characterised in that 2 is selected from among tezosentan, bosentan, enrasentan, sixtasentan, T-0201 and BMS-193884.
7) Pharmaceutical composition according to one of claims 1 to 6, characterised in that the weight ratios of 1 to 2 are in the range from 1:300 to 50:1, preferably from 1:250 to 40:1.
8) Pharmaceutical composition according to one of claims 1 to 7, characterised in that a single application corresponds to a dosage of the active substance combination 1 and 2 of 0.1 to 10000µg, preferably from 0.1 to 8000µg.
9) Pharmaceutical composition according to one of claims 1 to 8, characterised in that it is present in the form of a formulation suitable for inhalation.
10) Pharmaceutical composition according to claim 9, characterised in that it is a formulation selected from among inhalable powders, propellant-containing metering aerosols and propellant-free inhalable solutions or suspensions.
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) Capsules, characterised in that they contain an inhalable powder according to claim 11 or 12.
14) 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.
15) 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.
16) Propellant-containing inhalable aerosol according to claim 15, characterised in that it contains, as propellant gas, hydrocarbons such as n-propane, n-butane or isobutane or halohydrocarbons such as preferably fluorinated derivatives of methane, ethane, propane, butane, cyclopropane or cyclobutane.
17) Propellant-containing inhalable aerosol according to claim 16, characterised in that the propellant gas is TG134a, TG227 or a mixture thereof.
18) Propellant-containing inhalable aerosol according to claim 15, 16 or 17, characterised in that it optionally contains one or more other ingredients selected from among cosolvents, stabilisers, surfactants, antioxidants, lubricants and means for adjusting the pH.
19) Propellant-containing inhalable aerosol according to one of claims 15 to 18, characterised in that it may contain up to 5 wt.-% of active substance 1 and/or 2.
20) Pharmaceutical composition according to claim 10, characterised in that it is a propellant-free inhalable solution or suspension which contains water, ethanol or a mixture of water and ethanol as solvent.
21) Inhalable solution or suspension according to claim 20, characterised in that the pH is 2 - 7, preferably 2 - 5.
22) Inhalable solution or suspension according to claim 21, characterised in that the pH is adjusted by means of an acid selected from among hydrochloric acid, hydrobromic acid, nitric acid, sulphuric acid, ascorbic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid and propionic acid or mixtures thereof.
23) Inhalable solution or suspension according to one of claims 20 to 22, characterised in that it optionally contains other co-solvents and/or excipients.
24) Inhalable solution or suspension according to claim 23, 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.
25) Inhalable solution or suspension according to one of claims 23 or 24, characterised in that it contains as excipients surfactants, stabilisers, complexing agents, antioxidants and/or preservatives, flavourings, pharmacologically acceptable salts and/or vitamins.
26) Inhalable solution or suspension according to claim 25, characterised in that it contains as complexing agent editic acid or a salt of editic acid, preferably sodium edetate.
27 27) Inhalable solution or suspension according to claim 25 or 26, characterised in that it contains, as antioxidants, compounds selected from among ascorbic acid, vitamin A, vitamin E and tocopherols.
28) Inhalable solution or suspension according to claim 25, 26 or 27, characterised in that it contains as preservatives compounds selected from cetyl pyridinium chloride, benzalkonium chloride, benzoic acid and benzoates.
29) Inhalable solution or suspension according to one of claims 23 to 28, characterised in that it contains, in addition to the active substances 1 and 2 and the solvent, only benzalkonium chloride and sodium edetate.
30) Inhalable solution or suspension according to one of claims 23 to 28, characterised in that it contains, in addition to the active substances 1 and 2 and the solvent, only benzalkonium chloride.
31) Inhalable solution or suspension according to one of claims 20 to 30, characterised in that it is a concentrate or a sterile ready-to-use inhalable solution or suspension.
32) Use of a capsule according to claim 13 in an inhaler, preferably in a Handyhaler.
33) Use of an inhalable solution according to one of claims 20 to 30 for nebulising in an inhaler according to WO 911/4468 or an inhaler as described in Figures 6a and 6b of WO 97/12687.
34) Use of an inhalable solution according to claim 31 for nebulising in an energy-operated free-standing or portable nebuliser which produces inhalable aerosols by means of ultrasound or compressed air in accordance with the Venturi principle or other principles.
35) Use of a composition according to one of claims 1 to 31 for preparing a medicament for treating inflammatory or obstructive diseases of the respiratory tract.
CA2441964A 2001-03-20 2002-03-07 New pharmaceutical compositions based on anticholinergics and endothelin antagonists Expired - Fee Related CA2441964C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10113366A DE10113366A1 (en) 2001-03-20 2001-03-20 Medicament for treating inflammatory or obstructive respiratory diseases, e.g. asthma or chronic obstructive pulmonary disease, containing synergistic combination of anticholinergic agent and endothelin antagonist
DE10113366.9 2001-03-20
PCT/EP2002/002494 WO2002074034A2 (en) 2001-03-20 2002-03-07 Novel medicament compositions based on anticholinergic agents and endothelin antagonists

Publications (2)

Publication Number Publication Date
CA2441964A1 true CA2441964A1 (en) 2002-09-26
CA2441964C CA2441964C (en) 2011-01-18

Family

ID=7678141

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2441964A Expired - Fee Related CA2441964C (en) 2001-03-20 2002-03-07 New pharmaceutical compositions based on anticholinergics and endothelin antagonists

Country Status (8)

Country Link
EP (1) EP1379225B1 (en)
JP (1) JP2004525920A (en)
AT (1) ATE514420T1 (en)
AU (1) AU2002254930A1 (en)
CA (1) CA2441964C (en)
DE (1) DE10113366A1 (en)
MX (1) MXPA03008406A (en)
WO (1) WO2002074034A2 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10214264A1 (en) * 2002-03-28 2003-10-16 Boehringer Ingelheim Pharma HFA suspension formulations of an anhydrate
GB0219660D0 (en) 2002-08-23 2002-10-02 Astrazeneca Ab Therapeutic use
US20040265238A1 (en) * 2003-06-27 2004-12-30 Imtiaz Chaudry Inhalable formulations for treating pulmonary hypertension and methods of using same
GB0403744D0 (en) 2004-02-20 2004-03-24 Astrazeneca Ab Chemical process
WO2008088727A2 (en) 2007-01-12 2008-07-24 Concert Pharmaceuticals, Inc. Endothelin receptor antagonists
US8080549B2 (en) 2007-01-12 2011-12-20 Concert Pharmaceuticals, Inc. Endothelin receptor antagonists

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1177807A3 (en) * 1994-10-28 2003-10-22 Aradigm Corporation Device and method of creating aerosolized mist of respiratory drug

Also Published As

Publication number Publication date
EP1379225A2 (en) 2004-01-14
JP2004525920A (en) 2004-08-26
EP1379225B1 (en) 2011-06-29
WO2002074034A2 (en) 2002-09-26
WO2002074034A3 (en) 2003-10-23
AU2002254930A1 (en) 2002-10-03
MXPA03008406A (en) 2004-01-29
CA2441964C (en) 2011-01-18
ATE514420T1 (en) 2011-07-15
DE10113366A1 (en) 2002-09-26

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Effective date: 20130307