Thromboxane Receptor Antagonists in AERD/Asthma

Abstract

The present invention is directed to methods of treating AERD (aspirin exacerbated respiratory disease) and / or asthma via the administration of a thromboxane receptor antagonist to a patient in need thereof.

Description

FIELD OF THE INVENTION

[0001] The present invention is related to the use of thromboxane receptor antagonists (e.g., Ifetroban) in the treatment of AERD (aspirin exacerbated respiratory disease) and asthma; and pharmaceutical compositions for the treatment of the same.BACKGROUND OF THE INVENTION

[0002] Aspirin Exacerbated Respiratory Disease (AERD) is a chronic medical condition that consists of asthma, recurrent sinus disease with nasal polyps, as well as a sensitivity to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). Patients suffering from typically develop reactions triggered by aspirin or other NSAIDs. These reactions include, but are not limited to increased nasal congestion or stuffiness; eye watering or redness; cough, wheezing, or chest tightness; frontal headache or sensation of sinus pain; flushing and / or a rash; nausea and / or abdominal cramping; and a general feeling of malaise, sometimes accompanied by dizziness.

[0003] From a scientific perspective, AERD i...

Examples

example 1

[0082]In this example, ifetroban sodium tablets are prepared with the following ingredients listed in Table 1:

TABLE 1IngredientsPercent by weightNa salt of Ifetroban35Mannitol50Microcrystalline Cellulose8Crospovidone3.0Magnesium Oxide2.0Magnesium Stearate1.5Colloidal Silica0.3

[0083]The sodium salt of ifetroban, magnesium oxide, mannitol, microcrystalline cellulose, and crospovidone is mixed together for about 2 to about 10 minutes employing a suitable mixer. The resulting mixture is passed through a #12 to #40 mesh size screen. Thereafter, magnesium stearate and colloidal silica are added and mixing is continued for about 1 to about 3 minutes.

[0084]The resulting homogeneous mixture is then compressed into tablets each containing 35 mg, ifetroban sodium salt.

example ii

[0085]In this example, 1000 tablets each containing 400 mg of Ifetroban sodium are produced from the following ingredients listed in Table 2:

TABLE 2IngredientsAmountNa salt of Ifetroban400gmCorn Starch50gGelatin7.5gMicrocrystalline Cellulose (Avicel)25gMagnesium Stearate2.5g

example iii

[0086]In this example. An injectable solution of ifetroban sodium is prepared for intravenous use with the following ingredients listed in Table 3:

TABLE 3IngredientsAmountIfetroban Sodium2500mgMethyl Paraben5mgPropyl Paraben1mgSodium Chloride25,000mgWater for injection q.s.5liter

[0087]The sodium salt of ifetroban, preservatives and sodium chloride are dissolved in 3 liters of water for injection and then the volume is brought up to 5 liters. The solution is filtered through a sterile filter and aseptically filled into pre-sterilized vials which are then closed with pre-sterilized rubber closures. Each vial contains a concentration of 75 mg of active ingredient per 150 ml of solution.

FIELD OF THE INVENTION

[0001] The present invention is related to the use of thromboxane receptor antagonists (e.g., Ifetroban) in the treatment of AERD (aspirin exacerbated respiratory disease) and asthma; and pharmaceutical compositions for the treatment of the same.BACKGROUND OF THE INVENTION

[0002] Aspirin Exacerbated Respiratory Disease (AERD) is a chronic medical condition that consists of asthma, recurrent sinus disease with nasal polyps, as well as a sensitivity to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). Patients suffering from typically develop reactions triggered by aspirin or other NSAIDs. These reactions include, but are not limited to increased nasal congestion or stuffiness; eye watering or redness; cough, wheezing, or chest tightness; frontal headache or sensation of sinus pain; flushing and / or a rash; nausea and / or abdominal cramping; and a general feeling of malaise, sometimes accompanied by dizziness.

[0003] From a scientific perspective, AERD i...

Examples

example 1

[0082]In this example, ifetroban sodium tablets are prepared with the following ingredients listed in Table 1:

TABLE 1IngredientsPercent by weightNa salt of Ifetroban35Mannitol50Microcrystalline Cellulose8Crospovidone3.0Magnesium Oxide2.0Magnesium Stearate1.5Colloidal Silica0.3

[0083]The sodium salt of ifetroban, magnesium oxide, mannitol, microcrystalline cellulose, and crospovidone is mixed together for about 2 to about 10 minutes employing a suitable mixer. The resulting mixture is passed through a #12 to #40 mesh size screen. Thereafter, magnesium stearate and colloidal silica are added and mixing is continued for about 1 to about 3 minutes.

[0084]The resulting homogeneous mixture is then compressed into tablets each containing 35 mg, ifetroban sodium salt.

example ii

[0085]In this example, 1000 tablets each containing 400 mg of Ifetroban sodium are produced from the following ingredients listed in Table 2:

TABLE 2IngredientsAmountNa salt of Ifetroban400gmCorn Starch50gGelatin7.5gMicrocrystalline Cellulose (Avicel)25gMagnesium Stearate2.5g

example iii

[0086]In this example. An injectable solution of ifetroban sodium is prepared for intravenous use with the following ingredients listed in Table 3:

TABLE 3IngredientsAmountIfetroban Sodium2500mgMethyl Paraben5mgPropyl Paraben1mgSodium Chloride25,000mgWater for injection q.s.5liter

[0087]The sodium salt of ifetroban, preservatives and sodium chloride are dissolved in 3 liters of water for injection and then the volume is brought up to 5 liters. The solution is filtered through a sterile filter and aseptically filled into pre-sterilized vials which are then closed with pre-sterilized rubber closures. Each vial contains a concentration of 75 mg of active ingredient per 150 ml of solution.

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