WO1997028797A1 - Method of treatment and pharmaceutical composion - Google Patents

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

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

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

N-[4-oxo-2-(lH-tetrazol-5-yl)-4H-l-benzopyran-8-yl]-p-(4- phenylbutoxy)benzamide. EP 173,516

Pranlukast

Cyclopentyl- 3- [2-methoxy-4- [(o-tol ylsulf ony l)carbamoyl] - benzyl]- l-methylindole-5-carbamate. EP 199,543

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.