WO2001032163A1 - NEW COMBINATION COMPRISING A BETA 2 (β)2 ADRENO RECEPTOR AGONIST AND A LENKOTRIENE RECEPTOR ANTAGONIST - Google Patents

NEW COMBINATION COMPRISING A BETA 2 (β)2 ADRENO RECEPTOR AGONIST AND A LENKOTRIENE RECEPTOR ANTAGONIST Download PDF

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Publication number
WO2001032163A1
WO2001032163A1 PCT/SE2000/002115 SE0002115W WO0132163A1 WO 2001032163 A1 WO2001032163 A1 WO 2001032163A1 SE 0002115 W SE0002115 W SE 0002115W WO 0132163 A1 WO0132163 A1 WO 0132163A1
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WIPO (PCT)
Prior art keywords
active ingredient
pharmaceutically acceptable
zafirlukast
acceptable derivatives
formoterol
Prior art date
Application number
PCT/SE2000/002115
Other languages
French (fr)
Inventor
Jan Trofast
Original Assignee
Astrazeneca Ab
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 Astrazeneca Ab filed Critical Astrazeneca Ab
Priority to IL14936500A priority Critical patent/IL149365A0/en
Priority to KR1020027005683A priority patent/KR20020050254A/en
Priority to EP00975117A priority patent/EP1242065A1/en
Priority to MXPA02004334A priority patent/MXPA02004334A/en
Priority to BR0015172-6A priority patent/BR0015172A/en
Priority to AU13214/01A priority patent/AU1321401A/en
Priority to CA002388657A priority patent/CA2388657A1/en
Priority to JP2001534368A priority patent/JP2003513037A/en
Publication of WO2001032163A1 publication Critical patent/WO2001032163A1/en
Priority to NO20022103A priority patent/NO20022103D0/en

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    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • 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
    • 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
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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]

Definitions

  • esters examples include lower alkyl (Ci-C ⁇ alkyl) esters.
  • Examples of pharmaceutically acceptable solvates include hydrates.
  • the active ingredients may, and indeed usually will, be used in admixture with one or more pharmaceutically acceptable ingredients which may be selected, for example, from adjuvants, carriers, binders, lubricants, diluents, stabilising agents, buffering agents, emulsifying agents, viscosity-regulating agents, surfactants, preservatives, flavourings and colorants.
  • pharmaceutically acceptable ingredients which may be selected, for example, from adjuvants, carriers, binders, lubricants, diluents, stabilising agents, buffering agents, emulsifying agents, viscosity-regulating agents, surfactants, preservatives, flavourings and colorants.
  • Metered dose inhaler, nebuliser and dry powder inhaler devices are well known and a variety of such devices are available.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pulmonology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Otolaryngology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention provides a pharmaceutical composition, pharmaceutical product or kit comprising a first active ingredient which is a beta2 (β2) adrenoreceptor agonist and a second active ingredient which is a leukotriene receptor antagonist, for use in the treatment of inflammatory disorders.

Description

NEW COMBINATION COMPRISING A BETA 2 (β2) ADRENO RECEPTOR AGONIST AND A LENKOTRIENE RECEPTIOR ANTAGONIST
The present invention relates to combinations of pharmaceutically active substances for use in the treatment of inflammatory conditions/disorders, especially respiratory diseases.
There are many different inflammatory mediators implicated in the pathogenesis of respiratory diseases such as asthma. However, drugs that are used to treat respiratory diseases are not always very selective for the pathological features of these diseases. Thus, whilst glucocorticosteroid therapy has been found to be highly effective in the management of asthma, glucocorticosteroids have broad and nonspecific actions and, when taken orally, can produce serious side-effects. Inhaled glucocorticosteroids, on the other hand, are much less likely to cause serious side-effects.
In view of the complexity of respiratory diseases like asthma, it is unlikely that any one mediator can satisfactorily treat the disease alone.
Thus, it would be desirable to develop new pharmaceuticals which can provide a more effective treatment of inflammatory conditions.
In accordance with the present invention, there is therefore provided a pharmaceutical composition comprising, in admixture, a first active ingredient which is a beta2 2) adrenoreceptor agonist selected from formoterol and pharmaceutically acceptable derivatives thereof, and a second active ingredient which is a leukotriene receptor antagonist selected from zafirlukast, montelukast and their pharmaceutically acceptable derivatives.
In the context of the present specification, unless otherwise stated, a pharmaceutically acceptable derivative of formoterol (also known as eformoterol) means a pharmaceutically acceptable ester, salt or solvate of formoterol (e.g. formoterol fumarate) or a pharmaceutically acceptable solvate of such an ester or salt (e.g. formoterol fumarate dihydrate). A pharmaceutically acceptable derivative of zafirlukast or montelukast should be construed likewise (e.g. montelukast sodium).
Examples of suitable esters include lower alkyl (Ci-Cό alkyl) esters.
Pharmaceutically acceptable salts include, where applicable, acid addition salts derived from pharmaceutically acceptable inorganic and organic acids such as a chloride, bromide, sulphate, phosphate, maleate, fumarate, tartrate, citrate, benzoate, 4-methoxybenzoate, 2- or 4-hydroxybenzoate, 4-chlorobenzoate, p-toluenesulphonate, methanesulphonate, ascorbate, acetate, succinate, lactate, glutarate, gluconate, tricarballylate, hydroxynaphthalene-carboxylate or oleate salt; and salts prepared from pharmaceutically acceptable inorganic and organic bases. Salts derived from inorganic bases include aluminium, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic, manganous, potassium, sodium, zinc and bismuth salts. Particularly preferred are the ammonium, calcium, magnesium, potassium and sodium salts. Salts derived from pharmaceutically acceptable organic bases include salts of primary, secondary and tertiary amines, cyclic amines like arginine, betaine, choline and the like.
Examples of pharmaceutically acceptable solvates include hydrates.
Certain of the active ingredients used in the present invention are capable of existing in stereoisomeric forms. It will be understood that the invention encompasses all geometric and optical isomers of the active ingredients and mixtures thereof including racemates. Tautomers and mixtures thereof also form an aspect of the present invention.
The invention also provides a pharmaceutical product comprising, in combination, a preparation of a first active ingredient which is a beta2 ) adrenoreceptor agonist selected from formoterol and pharmaceutically acceptable derivatives thereof, and a preparation of a second active ingredient which is a leukotriene receptor antagonist selected from zafirlukast, montelukast and their pharmaceutically acceptable derivatives, for simultaneous, sequential or separate use in therapy.
In another aspect, the invention provides a kit comprising a preparation of a first active ingredient which is a beta2 (β2) adrenoreceptor agonist selected from formoterol and pharmaceutically acceptable derivatives thereof, a preparation of a second active ingredient which is a leukotriene receptor antagonist selected from zafirlukast, montelukast and their pharmaceutically acceptable derivatives, and instructions for the simultaneous, sequential or separate administration of the preparations to a patient in need thereof.
It has been found that the choice of active ingredients according to the invention is advantageous because it results in a beneficial anti-inflammatory and bronchodilator effect and, accordingly, can be used to treat various acute and chronic inflammatory conditions/disorders such as chronic obstructive pulmonary disease (COPD); asthma, such as bronchial, allergic, intrinsic, extrinsic and dust asthma, particularly chronic or inveterate asthma (e.g. late asthma and airways hyper-responsiveness); rhinitis and rheumatic arthritis.
The pharmaceutical composition of the invention may be prepared by mixing the first active ingredient with the second active ingredient. Therefore, in a further aspect of the present invention, there is provided a process for the preparation of a pharmaceutical composition which comprises mixing a first active ingredient which is a beta2 (fø) adrenoreceptor agonist selected from formoterol and pharmaceutically acceptable derivatives thereof, with a second active ingredient which is a leukotriene receptor antagonist selected from zafirlukast, montelukast and their pharmaceutically acceptable derivatives.
The first and second active ingredients may alternatively be administered simultaneously (other than in admixture as described above), sequentially or separately to treat inflammatory conditions. By sequential is meant that the first and second active ingredients are administered one immediately after the other. They still have the desired effect if they are administered separately but less than about 4 hours apart, preferably less than about 2 hours apart, more preferably less than about 30 minutes apart.
The active ingredients may, and indeed usually will, be used in admixture with one or more pharmaceutically acceptable ingredients which may be selected, for example, from adjuvants, carriers, binders, lubricants, diluents, stabilising agents, buffering agents, emulsifying agents, viscosity-regulating agents, surfactants, preservatives, flavourings and colorants.
For the above-mentioned therapeutic uses the dosages administered will, of course, vary with the first and second active ingredients employed, the mode of administration, the treatment desired and the disorder indicated. However, in general, satisfactory results will be obtained when the total daily dosage of first active ingredient(s) when taken by oral inhalation is in the range from 1 to 50 μg, particularly from 1, 2, 3, 4 or 5 to 48, preferably to 40, more preferably to 24 μg, and the total daily dosage of second active ingredient(s) when taken by oral inhalation is in the range from 1 to 800 μg, particularly from 1, 2, 5, 10 or 20 to 400, preferably to 200 μg.
The pharmaceutical composition, pharmaceutical product or kit according to the invention may be administered as divided doses from 1 to 4 times a day, and preferably once or twice a day.
The first and second active ingredients are conveniently administered topically (to the lung and/or airways) in the form of solutions, suspensions, aerosols and dry powder formulations.
For example metered dose inhaler devices may be used to administer the active ingredient(s), dispersed in a suitable propellant and with or without additional excipients such as ethanol, surfactants, lubricants or stabilising agents. Suitable propellants include hydrocarbon, chlorofluorocarbon and hydrofluoroalkane (e.g. heptafluoroalkane) propellants, or mixtures of any such propellants. Especially preferred propellants are PI 34a and P227, each of which may be used alone or in combination with other propellants and/or surfactants and/or other excipients.
Nebulised aqueous suspensions or, preferably, solutions may also be employed, with or without a suitable pH and/or tonicity adjustment, either as a unit-dose or multi-dose formulations.
Dry powder inhalers may be used to administer the active ingredient(s), alone or in combination with a pharmaceutically-acceptable carrier, in the latter case either as a finely divided powder or as an ordered mixture. The dry powder inhaler may be single dose or multi-dose and may utilise a dry powder or a powder-containing capsule.
Metered dose inhaler, nebuliser and dry powder inhaler devices are well known and a variety of such devices are available.
The present invention further provides the use of a pharmaceutical composition, pharmaceutical product or kit according to the invention in the manufacture of a medicament for the treatment of an inflammatory disorder.
Also, the present invention provides a method of treating an inflammatory disorder which comprises administering a therapeutically effective amount of a pharmaceutical composition of the invention to a patient in need thereof.
Still further, the present invention provides a method of treating an inflammatory disorder which comprises simultaneously, sequentially or separately administering: (a) a (therapeutically effective) dose of a first active ingredient which is a beta2 (β2) adrenoreceptor agonist selected from formoterol and pharmaceutically acceptable derivatives thereof; and
(b) a (therapeutically effective) dose of a second active ingredient which is a leukotriene receptor antagonist selected from zafirlukast, montelukast and their pharmaceutically acceptable derivatives, to a patient in need thereof.
In the context of the present specification, the term "therapy" also includes "prophylaxis" unless there are specific indications to the contrary. The terms "therapeutic" and "therapeutically" should be construed accordingly.
Prophylaxis is expected to be particularly relevant to the treatment of persons who have suffered a previous episode of, or are otherwise considered to be at increased risk of, the disease or condition in question. Persons at risk of developing a particular disease or condition generally include those having a family history of the disease or condition, or those who have been identified by genetic testing or screening to be particularly susceptible to developing the disease or condition.
The present invention will now be further understood by reference to the following illustrative examples. The examples describe certain pharmaceutical compositions which may be prepared as dry powder formulations for oral inhalation.
Example 1
Formoterol fumarate dihydrate 4.5 μg
Zafirlukast 100 μg
Lactose monohydrate 200 - 2000 μg Example 2
Formoterol fumarate dihydrate 9.0 μg
Zafirlukast 100 μg
5 Lactose monohydrate 200 - 2000 μg
Example 3
Formoterol fumarate dihydrate 4.5 μg io Zafirlukast 200 μg
Lactose monohydrate 300 - 2000 μg
Example 4
15 Formoterol fumarate dihydrate 9.0 μg
Zafirlukast 200 μg
Lactose monohydrate 300 - 2000 μg
Example 5 znu
Formoterol fumarate dihydrate 4.5 μg
Montelukast sodium 50 μg
Lactose monohydrate 200 - 2000 μg
25 Example 6
Formoterol fumarate dihydrate 4.5 μg
Montelukast sodium 100 μg
Lactose monohydrate 200 - 2000 μg

Claims

C L A I M S
1. A pharmaceutical composition comprising, in admixture, a first active ingredient which is a beta2 (β2) adrenoreceptor agonist selected from formoterol and pharmaceutically acceptable derivatives thereof, and a second active ingredient which is a leukotriene receptor antagonist selected from zafirlukast, montelukast and their pharmaceutically acceptable derivatives.
2. A composition according to claim 1, wherein the first or second active ingredient is in the form of a pharmaceutically acceptable salt, ester, solvate or solvate of an ester or salt.
3. A composition according to claim 1 or claim 2, wherein the first active ingredient is formoterol fumarate dihydrate.
4. A composition according to claim 1 , wherein the second active ingredient is zafirlukast.
5. A composition according to claim 1, wherein the second active ingredient is montelukast sodium.
6. A composition according to any one of claims 1 to 5 which is formulated for administration by oral inhalation.
7. Use of a composition according to claim 1 in the manufacture of a medicament for the treatment of an inflammatory disorder.
8. A process for the preparation of a pharmaceutical composition as defined in claim 1 which comprises mixing the first active ingredient with the second active ingredient.
9. A method of treating an inflammatory disorder which comprises administering a therapeutically effective amount of a pharmaceutical composition as defined in claim 1 to a patient in need thereof.
10. A method according to claim 9, wherein the inflammatory disorder is asthma or chronic obstructive pulmonary disease.
11. A pharmaceutical product comprising, in combination, a preparation of a first active ingredient which is a beta2 (β2) adrenoreceptor agonist selected from formoterol and pharmaceutically acceptable derivatives thereof, and a preparation of a second active ingredient which is a leukotriene receptor antagonist selected from zafirlukast, montelukast and their pharmaceutically acceptable derivatives, for simultaneous, sequential or separate use in therapy.
12. A product according to claim 11 , wherein the first or second active ingredient is in the form of a pharmaceutically acceptable salt, ester, solvate or solvate of an ester or salt.
13. A product according to claim 11 or claim 12, wherein the first active ingredient is formoterol fumarate dihydrate.
14. A product according to claim 11, wherein the second active ingredient is zafirlukast.
15. A product according to claim 11, wherein the second active ingredient is montelukast sodium.
16. Use of a product according to claim 11 in the manufacture of a medicament for the treatment of an inflammatory disorder.
17. A kit comprising a preparation of a first active ingredient which is a beta2 2) adrenoreceptor agonist selected from formoterol and pharmaceutically acceptable derivatives thereof, a preparation of a second active ingredient which is a leukotriene receptor antagonist selected from zafirlukast, montelukast and their pharmaceutically acceptable derivatives, and instructions for the simultaneous, sequential or separate administration of the preparations to a patient in need thereof.
18. A kit according to claim 17, wherein the first or second active ingredient is in the form of a pharmaceutically acceptable salt, ester, solvate or solvate of an ester or salt.
19. A kit according to claim 17 or claim 18, wherein the first active ingredient is formoterol fumarate dihydrate.
20. A kit according to claim 17, wherein the second active ingredient is zafirlukast.
21. A kit according to claim 17, wherein the second active ingredient is montelukast sodium.
22. Use of a kit according to claim 17 in the manufacture of a medicament for the treatment of an inflammatory disorder.
23. A method of treating an inflammatory disorder which comprises simultaneously, sequentially or separately administering:
(a) a dose of a first active ingredient which is a beta2 2) adrenoreceptor agonist selected from formoterol and pharmaceutically acceptable derivatives thereof; and
(b) a dose of a second active ingredient which is a leukotriene receptor antagonist selected from zafirlukast, montelukast and their pharmaceutically acceptable derivatives, to a patient in need thereof.
PCT/SE2000/002115 1999-11-03 2000-10-27 NEW COMBINATION COMPRISING A BETA 2 (β)2 ADRENO RECEPTOR AGONIST AND A LENKOTRIENE RECEPTOR ANTAGONIST WO2001032163A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
IL14936500A IL149365A0 (en) 1999-11-03 2000-10-27 NEW COMBINATION COMPRISING A BETA 2(β)2 ADRENO RECEPTOR AGONIST AND A LEUKOTRIENE RECEPTOR ANTAGONIST
KR1020027005683A KR20020050254A (en) 1999-11-03 2000-10-27 New Combination Comprising a Beta 2 (β2) Adreno Receptor Agonist and a Leukotriene Receptor Antagonist
EP00975117A EP1242065A1 (en) 1999-11-03 2000-10-27 New combination comprising a beta 2 (beta)2 adreno receptor agonist and a leukotriene receptor antagonist
MXPA02004334A MXPA02004334A (en) 1999-11-03 2000-10-27 NEW COMBINATION COMPRISING A BETA 2 (bgr;)2.
BR0015172-6A BR0015172A (en) 1999-11-03 2000-10-27 New combination comprising a beta 2 adrenaline agonist (beta 2) and a leukotriene receptor antagonist
AU13214/01A AU1321401A (en) 1999-11-03 2000-10-27 New combination comprising a beta 2 (beta)2 adreno receptor agonist and a leukotriene receptor antagonist
CA002388657A CA2388657A1 (en) 1999-11-03 2000-10-27 New combination comprising a beta 2 (.beta.)2 adreno receptor agonist and a leukotriene receptor antagonist
JP2001534368A JP2003513037A (en) 1999-11-03 2000-10-27 Novel combination comprising β2 (β2) adreno receptor agonist and leukotriene antagonist
NO20022103A NO20022103D0 (en) 1999-11-03 2002-05-02 New combination including a beta 2 (<beta>) 2 andrenoreceptor agonist and leukotriene receptor antagonist

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9903995A SE9903995D0 (en) 1999-11-03 1999-11-03 New combination
SE9903995-0 1999-11-03

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WO2001032163A1 true WO2001032163A1 (en) 2001-05-10

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PCT/SE2000/002116 WO2001032166A1 (en) 1999-11-03 2000-10-27 NEW COMBINATION COMPRISING A β2-ADRENORECEPTOR AGONIST AND A LEUKOTRIENE RECEPTOR ANTAGONIST
PCT/SE2000/002115 WO2001032163A1 (en) 1999-11-03 2000-10-27 NEW COMBINATION COMPRISING A BETA 2 (β)2 ADRENO RECEPTOR AGONIST AND A LENKOTRIENE RECEPTOR ANTAGONIST

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EP (1) EP1242065A1 (en)
JP (1) JP2003513037A (en)
KR (1) KR20020050254A (en)
CN (1) CN1387431A (en)
AU (2) AU1321401A (en)
BR (1) BR0015172A (en)
CA (1) CA2388657A1 (en)
IL (1) IL149365A0 (en)
MX (1) MXPA02004334A (en)
NO (1) NO20022103D0 (en)
SE (1) SE9903995D0 (en)
WO (2) WO2001032166A1 (en)
ZA (1) ZA200203178B (en)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6667344B2 (en) 2001-04-17 2003-12-23 Dey, L.P. Bronchodilating compositions and methods
WO2004105727A2 (en) * 2003-05-28 2004-12-09 Aventis Pharma Limited Stabilized pharmaceutical product
WO2005097095A1 (en) * 2004-04-05 2005-10-20 Sepracor Inc. (r,r)-formoterol in combination with other pharmacological agents
JP2005539027A (en) * 2002-08-09 2005-12-22 ノバルティス アクチエンゲゼルシャフト Benzothiazole derivatives having beta-2-adrenoceptor agonist activity
ES2245612A1 (en) * 2004-06-29 2006-01-01 Universidad De Barcelona Use of formoterol in the prophylactic and/or therapeutic treatment of muscle wasting and/or cachectic syndrome which are associated with catabolic conditions of certain diseases, such as cancer, aids, infections, diabetes and others
US7947744B2 (en) 2003-07-08 2011-05-24 Nycomed Gmbh Stable pharmaceutical products
US20130005716A1 (en) * 2011-06-06 2013-01-03 Chiesi Farmaceutici S.P.A. Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors
US20140155391A1 (en) * 2012-12-05 2014-06-05 Chiesi Farmaceutici S.P.A. 1-phenyl-2-pyridinyl alkyl alcohol derivatives as phosphodiesterase inhibitors
US9597396B2 (en) 2001-04-17 2017-03-21 Mylan Specialty Lp Formoterol/steroid bronchodilating compositions and methods of use thereof
US10987305B2 (en) * 2015-12-15 2021-04-27 Cipla Limited Preparation of respirable zafirlukast particles

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4991693B2 (en) * 2005-03-16 2012-08-01 メダ ファーマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト Combinations of anticholinergics and leukotriene receptor antagonists for the treatment of respiratory diseases
JP5846185B2 (en) 2013-11-21 2016-01-20 大日本印刷株式会社 Through electrode substrate and semiconductor device using the through electrode substrate

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039970A1 (en) * 1997-03-13 1998-09-17 Merck & Co., Inc. Quinoline leukotriene antagonists
WO1999030703A1 (en) * 1997-12-12 1999-06-24 Astrazeneca Ab Use of formoterol in medicament for inflammation/allergy in upper airways

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE9604752D0 (en) * 1996-12-20 1996-12-20 Astra Ab Formulation and use

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039970A1 (en) * 1997-03-13 1998-09-17 Merck & Co., Inc. Quinoline leukotriene antagonists
WO1999030703A1 (en) * 1997-12-12 1999-06-24 Astrazeneca Ab Use of formoterol in medicament for inflammation/allergy in upper airways

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BRIAN J. LIPWORTH ET AL.: "Effects of adding a leukotriene antagonist or a long-acting beta2-agonist in asthmatic patients with the glycine-16 beta2-adrenoceptor genotype", AM. J. MED., vol. 109, no. 2, 2000, pages 114 - 121, XP002937228 *
JEAN-FRANCOIS DESSANGES ET AL.: "The effect of zafirlukast on repeptitive exercise-induced bronchoconstriction: The possible role of leukotrienes in exercise-induced refractoriness", J. ALLERGY. CLIN. IMMUNOL., vol. 104, no. 6, 1999, pages 1155 - 1161, XP002937226 *
JONATHAN A. LEFF ET AL.: "Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction", N. ENGL. J. MED., vol. 339, no. 3, 1988, pages 147 - 152, XP002937227 *
OWEN J. DEMPSEY ET AL.: "Additive bronchoprotective and bronchodilator effects with single doses of salmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids", CHEST, vol. 117, April 2000 (2000-04-01), pages 950 - 953, XP002937229 *

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* Cited by examiner, † Cited by third party
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US9597396B2 (en) 2001-04-17 2017-03-21 Mylan Specialty Lp Formoterol/steroid bronchodilating compositions and methods of use thereof
US6667344B2 (en) 2001-04-17 2003-12-23 Dey, L.P. Bronchodilating compositions and methods
JP2005539027A (en) * 2002-08-09 2005-12-22 ノバルティス アクチエンゲゼルシャフト Benzothiazole derivatives having beta-2-adrenoceptor agonist activity
US8440210B2 (en) 2003-05-28 2013-05-14 Takeda Gmbh Stabilized pharmaceutical product
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US7736673B2 (en) 2003-05-28 2010-06-15 Nycomed Gmbh Stabilized pharmaceutical product
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AU2005231479B2 (en) * 2004-04-05 2011-07-21 Sunovion Pharmaceuticals Inc. (R,R)-formoterol in combination with other pharmacological agents
AU2005231479C1 (en) * 2004-04-05 2012-03-15 Sunovion Pharmaceuticals Inc. (R,R)-formoterol in combination with other pharmacological agents
WO2005097095A1 (en) * 2004-04-05 2005-10-20 Sepracor Inc. (r,r)-formoterol in combination with other pharmacological agents
WO2006003222A1 (en) * 2004-06-29 2006-01-12 Universidad De Barcelona Use of formoterol in the prophylactic and/or therapeutic treatment of muscle wasting and/or cachectic syndrome which are associated with catabolic conditions of certain diseases, such as cancer, aids, infections, diabetes and others
ES2245612A1 (en) * 2004-06-29 2006-01-01 Universidad De Barcelona Use of formoterol in the prophylactic and/or therapeutic treatment of muscle wasting and/or cachectic syndrome which are associated with catabolic conditions of certain diseases, such as cancer, aids, infections, diabetes and others
US20130005716A1 (en) * 2011-06-06 2013-01-03 Chiesi Farmaceutici S.P.A. Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors
US20140057882A1 (en) * 2011-06-06 2014-02-27 Chiesi Farmaceutici S.P.A. Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors
US9931327B2 (en) 2011-06-06 2018-04-03 Chiesi Farmaceutici S.P.A. Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors
US20140155391A1 (en) * 2012-12-05 2014-06-05 Chiesi Farmaceutici S.P.A. 1-phenyl-2-pyridinyl alkyl alcohol derivatives as phosphodiesterase inhibitors
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US10987305B2 (en) * 2015-12-15 2021-04-27 Cipla Limited Preparation of respirable zafirlukast particles

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JP2003513037A (en) 2003-04-08

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