Composition and method for treating allergic diseases

• US 6,221,880 B1
• Filed: 10/06/1999
• Issued: 04/24/2001
• Est. Priority Date: 10/09/1998
• Status: Expired due to Fees

• Current Assignee: Schering Corporation (Merck & Co., Inc.)
• Original Assignee: Schering Corporation (Merck & Co., Inc.)
• Inventors: Shih, Neng-Yang
• Primary Examiner(s): Jarvis, William R. A.
• Assistant Examiner(s): KIM, VICKIE Y
• Application Number:
  US09/413,025
• Time in Patent Office: 566 Days
• Field of Search: 514/311, 514/415, 514/382, 514/316
• US Class Current: 514/311
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines

Abstract

The present invention is directed towards a pharmaceutical composition useful for the treatment allergic rhinitis, asthma and related disorders. In one embodiment, the composition comprises, in combination, a therapeutically effective amount of at least one neurokinin antagonist, and a therapeutically effective amount of at least one 5-lipoxygenase inhibitor.

Claims

1. A pharmaceutical composition comprising, in combination, a therapeutically effective amount of at least one neurokinin antagonist or a pharmaceutically acceptable derivative thereof, and a therapeutically effective amount of at least one leukotriene antagonist or a pharmaceutically acceptable derivative thereof, wherein said neurokinin antagonist is a compound having the general formula:

where B is OR₂;

NR₆COR₂, CONR₆R₇ or NR₂CONR₆R₇,

m=0 or 1,

P is R₅-aryl;

or R₅-heteroaryl; and

Y is H, CR₂R₃CO₂R₆;

CR₂R₃CONR₆R₇ or CR₂R₃NR₆COR₂,

a═

b═

0, 1 or 2;

Q has the same definitions as P above, with the proviso that P and Q may be the same or different;

A is=N—

OR₁;

=N—

NR₂R₃;

or=CR₁R₂;

X is —

O—

;

—

NR₆—

;

—

N(R₆)CO—

;

or —

CO—

NR₆—

;

T is R₄-aryl;

R₄-heteroaryl;

R₄-cycloalkyl;

or R₂-bridged cycloalkyl;

R₁ is H, C₁-C₆ alkyl;

or (CH₂),-G where n═

1-6,

G is H;

R₄-aryl;

R₄-heteroaryl;

COR₆;

CO₂R₆;

CONR₆R₇;

CN;

OCOR₆;

SO₃R₂;

C(═

NOR₂)NR₆R₇;

C(=NR₂)NR₆R₇, with the proviso that when n≠

1, G can additionally be OR₆, NR₆R₇ or NR₆(CO)R₇;

R₂ and R₃ are independently H or C₁-C₆ alkyl;

R₄ and R₅ are independently 1, 2 or 3 substituents independently selected from OR₂, OC(O)R₂, OC(O)NR₆R₇, C₁-C₆ alkyl, H, halogen, CF₃, C₂F₅, or OCF₃; and

R₆ and R₇ are independently selected from H or C₁-C₆ alkyl, with the proviso that when R₆ and R₇ are part of NR₆R₇ then said NR₆R₇ may form part of a C₅-C₆ ring wherein 0-2 ring members are selected from the group consisting of —

O—

, —

S—

and —

NR₂—

, with the further proviso that said C₅-C₆ ring may contain substituents on said ring, with said substituents being selected from the group consisting of hydrogen, halogen, —

OR₆ and —

COOR₆.

2. The pharmaceutical composition of claim 1, wherein said neurokinin antagonist or its pharmaceutically acceptable derivative is present in amounts of 1-1,000 milligrams per unit dosage of said pharmaceutical composition.

3. The pharmaceutical composition of claim 1, wherein said neurokinin antagonist or its pharmaceutically acceptable derivative is present in amounts of 10-500 milligrams per unit dosage of said pharmaceutical composition.

4. The pharmaceutical composition of claim 1, wherein said neurokinin antagonist or its pharmaceutically acceptable derivative is present in amounts of 50-200 milligrams per unit dosage of said pharmaceutical composition.

5. The pharmaceutical composition of claim 1, wherein said leukotriene antagonist or its pharmaceutically acceptable derivative is present in amounts of 2-500 milligrams per unit dosage of said pharmaceutical composition.

6. The pharmaceutical composition of claim 1, wherein said leukotriene antagonist or its pharmaceutically acceptable derivative is present in amounts of 5-100 milligrams per unit dosage of said pharmaceutical composition.

7. The pharmaceutical composition of claim 1, wherein said leukotriene antagonist or its pharmaceutically acceptable derivative is present in amounts of 10-50 milligrams per unit dosage of said pharmaceutical composition.

8. The pharmaceutical composition of claim 1, wherein said neurokinin antagonist is a compound having the general formula:

and stereoisomers thereof, where R═

H;

CH₂CONH₂;

CH₂CONHMe;

CH₂CONMe₂ or

9. The pharmaceutical composition of claim 1, wherein said neurokinin antagonist is a compound having the general formula:

where R is H;

CH₂CONH₂;

CH₂CONHMe;

CH₂CONMe₂ or

10. The pharmaceutical composition of claim 9, wherein said neurokinin antagonist is the compound where R is CH₂CONH₂.

11. The pharmaceutical composition of claim 9, wherein said neurokinin antagonist is the compound where R is CH₂CONHMe.

12. The pharmaceutical composition of claim 11, wherein said leukotriene antagonist is selected from the group consisting of montelukast, montelukast sodium, pranlukast, zafirlukast and CP-195494.

13. The pharmaceutical composition of claim 12, wherein said leukotriene antagonist is montelukast sodium.

14. The pharmaceutical composition of claim 1, additionally containing one or more materials selected from the group consisting of a pharmaceutically acceptable carrier, a decongestant, a cough suppressant and an expectorant.

15. A method for the treatment of asthma, allergic rhinitis, chronic obstructive pulmonary disease, sneezing, itching runny nose, nasal congestion, redness of the eye, tearing, itching of the ears or palate, wheezing, coughs associated with postnasal drip symptoms and respiratory disorders associated with allergy in a mammalian organism in need of such treatment, said treatment comprising:

administering a pharmaceutical composition comprising, in combination, a therapeutically effective amount of at least one neurokinin antagonist or a pharmaceutically acceptable derivative thereof and a therapeutically effective amount of at least one leukotriene antagonist or a pharmaceutically acceptable derivative thereof, wherein said neurokinin antagonist is a compound stated in claim 1.