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Methods and compositions for treating respiratory disease

A composition and respiratory technology, applied in the field of treatment of respiratory diseases and composition, can solve problems such as side effects and unsafe treatment

Inactive Publication Date: 2011-03-02
TARGEGEN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, topical / topical administration of agents may end up in the GI tract
If the agent is orally bioavailable, systemic aggregation may occur, making treatment unsafe or producing some side effects, especially for highly potent drugs (IC 50 less than 500nM)

Method used

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  • Methods and compositions for treating respiratory disease
  • Methods and compositions for treating respiratory disease
  • Methods and compositions for treating respiratory disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1 Lung Exposure and Particle Size Analysis

[0056] 6,7-Bis(3-hydroxyphenyl)-pteridine-2,4-diamine (compound A) was formulated as a 20% suspension in 5% tyloxapol in water. use a colloid mill MK module, at 12,000 rpm for 6 hours while keeping the temperature below 50°C), resulting in particle size reduction. Samples of Compound A at 4%, 0.4%, 0.04%, and 0.004% were prepared by dilution with deionized water.

[0057] Nebulization of the suspension was performed using a Pari LC Plus @ 3 LPM with an active diluter at 5 LPM in a nose-only exposure chamber from CH technologies. Aerodynamic particle size was determined by a 7 stage impactor from Intox at 1 LPM. Stages were extracted with acetonitrile:water (1:1) containing 0.05% TFA and analyzed by HPCL against an external standard.

[0058] Estimated lung exposure was calculated based on the following assumptions: absorbable dose collected by a 7-stage impactor; 30 min exposure time; mouse minute volume (mouse m...

Embodiment 2

[0063] Example 2 Inhalation exposure (Inhalation exposure)

[0064] A series of compositions for pulmonary delivery were prepared by preparing a 20% suspension of Compound A in 5% tyloxapol in water. use a colloid mill MK module, at 12,000 rpm for 6 hours while keeping the temperature below 50°C), resulting in particle size reduction. A 4% w / v sample of compound A was prepared by dilution with deionized water.

[0065] Use low concentration (0.02mg / L), middle concentration (0.07mg / L) and high concentration (0.20mg / L) target aerosol: 0.3% compound A / 0.075% tyloxapol, 0.6% compound A / 0.15% four Suspension of tyloxapol and 1.5% compound A / 0.375% tyloxapol. These low, medium and high target formulations were prepared as follows:

[0066] Remove 4% Compound A and 1% tyxapol from the freezer, transfer approximately 2.25, 4.5, and 12 mL into clean 50 mL graduated plastic tubes, labeled 0.3% A / 0.075% tyxapol, 0.6% A / 0.15% tyloxapol and 1.5% A / 0.375% tyloxapol suspension, allowe...

Embodiment 3

[0088] The lung exposure of embodiment 3 mice

[0089] A series of compositions for pulmonary delivery were prepared by preparing a 20% suspension of Compound A in 5% tyloxapol in water. use a colloid mill MK module, at 12,000 rpm for 6 hours while keeping the temperature below 50°C), resulting in particle size reduction. A 4% sample of Compound A was prepared by dilution with deionized water. A 0.4% suspension of Compound A in 0.1% tyloxapol solution was obtained by dilution with sterile water for injection (SWFI) (6.02 g of a 20% suspension was topped up to 30.23 g with sterile water for injection).

[0090] Prepare each of the following solutions as described below:

[0091] 0.4% compound A suspension in 0.1% tyloxapol solution: 2.07 g of a 4% compound A suspension was diluted to 20 g with deionized water.

[0092] 0.04% compound A suspension in 0.01% tyloxapol solution: 2.03 g of a 0.4% compound A suspension was diluted to 20 g with deionized water.

[0093] 0.004% c...

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Abstract

The invention provides methods and compositions for treating asthma and / or COPD. For example, provided herein are compositions that include a kinase inhibiting agent such as 6,7-bis(3-hydroxyphenyl)-pteridine-2,4-diamine or pharmaceutically acceptable salts thereof; and a surfactant.

Description

[0001] Cross References to Related Applications [0002] This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application 61 / 027,180, filed February 8, 2008, the entire contents of which application are incorporated herein by reference. Background technique [0003] Airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) have been increasing in prevalence in recent years. The Centers for Disease Control and Prevention estimates that 17 million American adults are diagnosed with asthma and another 10 million with COPD. [0004] Asthma is a long-term lung disease characterized in part by lower airway inflammation and episodes of airflow obstruction. Asthma severity ranges from intermittent mild symptoms such as coughing and wheezing, to severe, life-threatening attacks that require immediate hospital treatment. Airway obstruction in asthma is generally considered reversible, meaning that the obstruction in the lungs usually reso...

Claims

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Application Information

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IPC IPC(8): A61K31/519A61P11/00A61P11/06
CPCA61K31/519A61P11/00A61P11/06A61P11/08A61P43/00
Inventor 路易斯·A·德拉马里迈克尔·B·马丁
Owner TARGEGEN
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