WO1997028797A1 - Method of treatment and pharmaceutical composion - Google Patents

Method of treatment and pharmaceutical composion Download PDF

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Publication number
WO1997028797A1
WO1997028797A1 PCT/US1997/001799 US9701799W WO9728797A1 WO 1997028797 A1 WO1997028797 A1 WO 1997028797A1 US 9701799 W US9701799 W US 9701799W WO 9728797 A1 WO9728797 A1 WO 9728797A1
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WO
WIPO (PCT)
Prior art keywords
phenyl
loratadine
pharmaceutical formulation
sodium
leukotriene antagonist
Prior art date
Application number
PCT/US1997/001799
Other languages
French (fr)
Inventor
Sven-Erik Dahlen
Edward M. Scolnick
Original Assignee
Merck & Co., Inc.
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
Priority claimed from GBGB9608927.1A external-priority patent/GB9608927D0/en
Priority to IL12544697A priority Critical patent/IL125446A0/en
Priority to EP97905757A priority patent/EP1014972A4/en
Priority to NZ331160A priority patent/NZ331160A/en
Priority to AU22579/97A priority patent/AU732671B2/en
Priority to JP9528627A priority patent/JPH11504044A/en
Priority to EA199800698A priority patent/EA199800698A1/en
Priority to BR9707369A priority patent/BR9707369A/en
Application filed by Merck & Co., Inc. filed Critical Merck & Co., Inc.
Priority to EE9800234A priority patent/EE9800234A/en
Priority to SK1056-98A priority patent/SK105698A3/en
Priority to UA98084549A priority patent/UA59359C2/en
Publication of WO1997028797A1 publication Critical patent/WO1997028797A1/en
Priority to IS4805A priority patent/IS4805A/en
Priority to BG102669A priority patent/BG102669A/en
Priority to NO983641A priority patent/NO983641D0/en

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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
    • A61K31/41—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
    • 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
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • 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
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4365—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Definitions

  • Loratadine is an antihistamine with H-receptor antagonist properties useful in the treatment of allergies and is described in U.S. Patent 4,282,233.
  • Leukotriene antagonists are known to be useful in the treatment of asthma, allergic reactions, and inflammation.
  • This invention is concerned with a method of treatment of asthma, allergy and inflammation by administration of an effective amount of loratadine and an effective amount of a leukotriene antagonist either by essentially concurrent administration or combined in a single pharmaceutical composition wherein the leukotriene antagonist is selected from:
  • the novel pharmaceutical composition of this invention comprises a combination of loratadine and a leukotriene antagonist selected from A, B, C, D and E, described above, as active ingredients, and optionally a pharmaeutically acceptable carrier suitable for enteral or parenteral administration.
  • the formulations may be in solid form, as for example tablets and capsules, or in liquid form, as for example, syrups, elixirs, emulsions and injectables.
  • excipients such as water, gelatin, lactose starches, magnesium stearate, talc, vegetable oils, benzyl alcohol, gums, polyalkylene glycols, and petroleum jelly.
  • a preferred formulation is mere fully described in the following Example.
  • the loratadine and leukotriene antagonist can be administered substantially concurrently as separate dosage forms or combined in the novel pharmaceutical formulation of this invention.
  • the preferred human oral dosage range is about 5 to 20 mg., loratadine, 1 to 3 times per day; preferably about 10 mg. once a day.
  • the human dosage range is also about 5 to 20 mg 1 to 3 times per day; preferably about 10 mg. once a day.

Abstract

A method of treating asthma, allergy and inflammation comprises treatment with a leukotriene inhibitor and loratadine either concurrently in separate doses or combined in a single pharmaceutical formulation.

Description

CROSS REFERENCE TO RELATED APPLICAΗON
This application is based on, and claims priority from, provisional application number 60/011,328 filed February 8, 1996.
TITLE OF THE INVENTION
METHOD OF TREATMENT AND PHARMACEUTICAL
COMPOSITION
BACKGROUND OF THE INVENTION
Loratadine is an antihistamine with H-receptor antagonist properties useful in the treatment of allergies and is described in U.S. Patent 4,282,233.
Leukotriene antagonists are known to be useful in the treatment of asthma, allergic reactions, and inflammation.
Now with the present invention, there is provided a method of treating asthma, allergy and inflammation with a combination of these two agents which is more efficacious than either agent by itself.
SUMMARY OF THE INVENTION
This invention is concerned with a method of treatment of asthma, allergy and inflammation by administration of an effective amount of loratadine and an effective amount of a leukotriene antagonist either by essentially concurrent administration or combined in a single pharmaceutical composition wherein the leukotriene antagonist is selected from:
A. Sodium 1 -(((R)-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3-(2- (2-hydroxy-2-propyl)phenyl)thio)methyl)cyclopropaneacetate, EP 480,717
Figure imgf000004_0001
Montelukast Sodium
Sodium l-(((R)-(3-(2-(6,7-difluoro-2-quinolinyl)ethenyl)- phenyl)-3-(2-(2-hydroxy-2-propyl)phenyl)thio)methyl)cyclo- propaneacetate. U.S. 5,270,324
Figure imgf000004_0002
l-(((l(R)-(3-(2-(2,3-dichlorothieno[3,2-b]pyridin-5-yl)-(E)- ethenyl)phenyl)-3-(2-( 1 -hydroxy- 1 -methylethyl)phenyl)- propyl)thio)methyl)cyclopropaneacetic acid or sodium salt thereof. U.S. 5,472,964
Figure imgf000005_0001
N-[4-oxo-2-(lH-tetrazol-5-yl)-4H-l-benzopyran-8-yl]-p-(4- phenylbutoxy)benzamide. EP 173,516
Figure imgf000005_0002
Pranlukast
Cyclopentyl- 3- [2-methoxy-4- [(o-tol ylsulf ony l)carbamoyl] - benzyl]- l-methylindole-5-carbamate. EP 199,543
Figure imgf000006_0001
Zafirlukast
DETAILED DESCRIPTION OF THE INVENTION
The novel pharmaceutical composition of this invention comprises a combination of loratadine and a leukotriene antagonist selected from A, B, C, D and E, described above, as active ingredients, and optionally a pharmaeutically acceptable carrier suitable for enteral or parenteral administration. The formulations may be in solid form, as for example tablets and capsules, or in liquid form, as for example, syrups, elixirs, emulsions and injectables. In the formulation of pharmaceutical dosage forms there generally is utilized excipients such as water, gelatin, lactose starches, magnesium stearate, talc, vegetable oils, benzyl alcohol, gums, polyalkylene glycols, and petroleum jelly. A preferred formulation is mere fully described in the following Example.
In the novel method of treatment of this invention, the loratadine and leukotriene antagonist can be administered substantially concurrently as separate dosage forms or combined in the novel pharmaceutical formulation of this invention.
Although the required dosage will be determined by such factors as the patients age, sex, weight and severity of the condition being treated, the preferred human oral dosage range is about 5 to 20 mg., loratadine, 1 to 3 times per day; preferably about 10 mg. once a day. In the case of the leukotrienes, the human dosage range is also about 5 to 20 mg 1 to 3 times per day; preferably about 10 mg. once a day. EXAMPLE
Montelukast Sodium 10 mg and Loratadine 10 mg Film Coated Tablet
Amt. Per Ingredient Tablet
Core
10.4 mg Montelukast Sodium
10.0 mg Loratadine
66.6 mg Microcrystalline Cellulose, NF
100.0 mg Lactose Monohydrate, NF
6.0 mg Croscarmellose Sodium, NF
(60.0 mg) Purified Water, USP
1.0 mg Magnesium Stearate, NF
200.0 mg Core Tablet
Film Coating
2.25 mg Hydroxypropyl Methylcellulose 6 cps
1.25 mg Hydroxypropyl Cellulose LF
1.50 mg Titanium Dioxide
(33.5) mg Purified Water
205.0 mg Film Coated Tablet

Claims

WHAT IS CLAIMED IS:
1. A pharmaceutical formulation comprising as active ingredients loratadine and a leukotriene antagonist selected from (A) montelukast sodium;
(B) Sodium l-(((R)-(3-(2-(6,7-difluoro-2-quinolinyl) ethenyl)phenyl) -3-(2-(2-hydroxy-2-propyl)phenyl) thio)methylcyclopropaneacetate;
(C) l-(((l(R)-(3-(2-(2,3-dichlorothieno[3,2-b]pyridin-5-yl)-(E)- ethenyl)phenyl)-3-(2-( 1 -hydroxy- 1 -methylethyl)phenyl)propyl) thio)methyl)cyclopropaneacetic acid or a sodium salt thereof;
(D) pranlukast; and
(E) zafϊrlukast; and a pharmaceutically acceptable carrier.
2. The composition of Claim 1 which is designed for oral administration.
3. The composition of Claim 2 comprising 10 mg of loratadine and 10 mg of a leukotriene antagonist selected from (A),
(B), (C), (D) and (E).
4. The composition of Claim 1, wherein the leukotriene antagonist is montelukast sodium.
5. The composition of Claim 4 which is designed for oral administration.
6. The composition of Claim 5, comprising 10 mg of each active ingredient.
7. A method of treating asthma, allergy and inflammation in a patient in need of such treatment by the administration of an effective amount of loratadine and an effective amount of a leukotriene antagonist selected from:
(A) montelukast sodium;
(B) sodium l-(((R)-(3-(2-(6,7-difluror-2-quinolinyl)ethenyl)phenyl)-3- (2-(2-hydroxy-2-propyl)phenyl)thio)methyl)cyclopropaneactate;
(C) l-(((l(R)-(3-(2-(2,3-dichlorothieno[3,2-b]pyridin-5-yl)-(E)- ethenyl)phenyl)-3-(2-( 1 -hydroxy- 1 -methylethyl)- phenyl)propyl)thio)methyl)cyclopropaneacetic acid or a sodium salt thereof; (D) pranlukast; and (E) zafirlukast; either substantially concurrently in separate dosage forms or combined in the single pharmaceutical formulation of Claim 1.
8. The method of Claim 7, wherein the pharmaceutical formulation is designed for oral administration.
9. The method of Claim 7 wherein the separate dosage forms and the single pharmaceutical formulation comprise 10 mg of loratadine and 10 mg of a leukotriene antagonist selected from (A), (B), (C), (D) and (E).
10. The method of Claim 7 wherein the leukotriene antagonist is (A) montelukast sodium.
11. The method of Claim 10 wherein the separate dosage forms and single pharmaceutical formulation are designed for oral administration.
12. The method of Claim 11 wherein the separate dosage forms and the single pharmaceutical formulation comprise 10 mg of loratadine and 10 mg of (A), montelukast sodium.
PCT/US1997/001799 1996-02-08 1997-02-04 Method of treatment and pharmaceutical composion WO1997028797A1 (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
SK1056-98A SK105698A3 (en) 1996-02-08 1997-02-04 Method of treatment and pharmaceutical composion
BR9707369A BR9707369A (en) 1996-02-08 1997-02-04 Pharmaceutical formulation and process for treating allergy and inflammation asthma in a patient
NZ331160A NZ331160A (en) 1996-02-08 1997-02-04 use of loratadine and a leukotriene antagonist to treat asthma
AU22579/97A AU732671B2 (en) 1996-02-08 1997-02-04 Method of treatment and pharmaceutical composition
JP9528627A JPH11504044A (en) 1996-02-08 1997-02-04 Treatment method and pharmaceutical preparation
EA199800698A EA199800698A1 (en) 1996-02-08 1997-02-04 METHOD OF TREATMENT AND PHARMACEUTICAL COMPOSITION
EE9800234A EE9800234A (en) 1996-02-08 1997-02-04 Method of treatment and pharmaceutical composition
IL12544697A IL125446A0 (en) 1996-02-08 1997-02-04 Pharmaceutical composition for the treatment of asthma allergy and inflammation
EP97905757A EP1014972A4 (en) 1996-02-08 1997-02-04 Method of treatment and pharmaceutical composion
UA98084549A UA59359C2 (en) 1996-02-08 1997-04-02 Pharmaceutical formulation and method for treating asthma, allergy and inflammation
IS4805A IS4805A (en) 1996-02-08 1998-07-22 Method of treatment and pharmaceutical composition
BG102669A BG102669A (en) 1996-02-08 1998-08-05 Method of treatment and pharmaceutical composition
NO983641A NO983641D0 (en) 1996-02-08 1998-08-07 METHOD OF TREATMENT AND PHARMACEUTICAL PREPARATION

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US1132896P 1996-02-08 1996-02-08
US60/011,328 1996-02-08
GBGB9608927.1A GB9608927D0 (en) 1996-04-29 1996-04-29 Method of treatment and pharmaceutical composition
GB9608927.1 1996-04-29

Publications (1)

Publication Number Publication Date
WO1997028797A1 true WO1997028797A1 (en) 1997-08-14

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PCT/US1997/001799 WO1997028797A1 (en) 1996-02-08 1997-02-04 Method of treatment and pharmaceutical composion

Country Status (19)

Country Link
EP (1) EP1014972A4 (en)
JP (1) JPH11504044A (en)
KR (1) KR19990082367A (en)
CN (1) CN1210465A (en)
AU (1) AU732671B2 (en)
BG (1) BG102669A (en)
BR (1) BR9707369A (en)
CA (1) CA2245162A1 (en)
CZ (1) CZ248798A3 (en)
EE (1) EE9800234A (en)
IL (1) IL125446A0 (en)
IS (1) IS4805A (en)
NO (1) NO983641D0 (en)
NZ (1) NZ331160A (en)
PL (1) PL328074A1 (en)
SK (1) SK105698A3 (en)
TR (1) TR199801511T2 (en)
WO (1) WO1997028797A1 (en)
YU (1) YU33298A (en)

Cited By (21)

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WO1999025338A1 (en) * 1997-11-14 1999-05-27 Astrazeneca Uk Limited Pharmaceutical composition containing zafirlukast
WO1999032125A1 (en) * 1997-12-23 1999-07-01 Schering Corporation Composition for treating respiratory and skin diseases, comprising at least one leukotriene antagonist and at least one antihistamine
WO2000006545A1 (en) * 1998-07-27 2000-02-10 Schering Corporation High affinity ligands for nociceptin receptor orl-1
WO2000015226A1 (en) * 1998-09-10 2000-03-23 Schering Corporation Antihistamines for treating non-infective sinusitis or otitis media
WO2000057880A1 (en) * 1999-03-29 2000-10-05 Schering Corporation Methods and compositions for treating allergic and related disorders using fluorinated descarboethoxyloratadine
US6194431B1 (en) 1998-04-14 2001-02-27 Paul D. Rubin Methods and compositions using terfenadine metabolites in combination with leukotriene inhibitors
US6248308B1 (en) 1998-04-14 2001-06-19 Sepracor Inc. Methods of using norastemizole in combination with leukotriene inhibitors to treat or prevent asthma
US6262066B1 (en) 1998-07-27 2001-07-17 Schering Corporation High affinity ligands for nociceptin receptor ORL-1
WO2001060407A2 (en) * 2000-02-17 2001-08-23 Viatris Gmbh & Co. Kg Novel combination of non-sedative anti-histamines containing substances which influence the action of leukotriene, for treating rhinitis/conjunctivitis
JP2002511425A (en) * 1998-04-14 2002-04-16 セプラコア インコーポレーテッド Methods and compositions for treating conditions responsive to leukotriene inhibition using cetirizine with a leukotriene inhibitor
WO2002036124A2 (en) * 2000-10-30 2002-05-10 Schering Corporation Treatment and method using loratadine and montelukast
WO2002080916A1 (en) * 2001-04-03 2002-10-17 Kaura Sita R Composition and method for the treatment of respiratory disease
WO2004087095A2 (en) * 2003-03-31 2004-10-14 Osmotica Costa Rica, Sociedad Anonima Osmotic controlled release device containing zafirlukast and an h1-antagonist
WO2005037245A2 (en) * 2003-10-21 2005-04-28 Direct-Haler A/S A multiple route medication for the treatment of rhinitis and asthma
WO2005089748A1 (en) * 2004-03-17 2005-09-29 Pfizer Limited Combination for treating inflammatory diseases
WO2006047427A1 (en) 2004-10-25 2006-05-04 Schering Corporation M1 and/or m3 receptor antagonists in combination with other actives for treating respiratory disorders
US7211582B1 (en) 1994-12-30 2007-05-01 Sepracor Inc. Methods for treating urticaria using descarboethoxyloratadine
US7214683B1 (en) 1994-12-30 2007-05-08 Sepracor Inc. Compositions of descarboethoxyloratadine
WO2010021607A3 (en) * 2008-08-22 2010-06-03 Mahmut Bilgic Pharmaceutical formulation
WO2010147947A2 (en) 2009-06-16 2010-12-23 Schering Corporation NOVEL [3,2-c] HETEROARYL STEROIDS AS GLUCOCORTICOID RECEPTOR AGONISTS, COMPOSITIONS AND USES THEREOF
WO2020143744A1 (en) * 2019-01-10 2020-07-16 Jiangyin Mucocare Pharmaceutical Co., Ltd. New formulations containing leukotriene receptor antagonists

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KR101540191B1 (en) * 2014-02-24 2015-07-28 성균관대학교산학협력단 Composition comprising Loratadine for anti-inflammation

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Cited By (41)

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Publication number Priority date Publication date Assignee Title
US7214683B1 (en) 1994-12-30 2007-05-08 Sepracor Inc. Compositions of descarboethoxyloratadine
US7214684B2 (en) 1994-12-30 2007-05-08 Sepracor Inc. Methods for the treatment of allergic rhinitis
US7211582B1 (en) 1994-12-30 2007-05-01 Sepracor Inc. Methods for treating urticaria using descarboethoxyloratadine
WO1999025338A1 (en) * 1997-11-14 1999-05-27 Astrazeneca Uk Limited Pharmaceutical composition containing zafirlukast
US6333361B1 (en) 1997-11-14 2001-12-25 Zeneca Limited Pharmaceutical composition containing zafirlukast
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