Dual Bronchodilator Inhalation Combination for Once-Daily COPD Relief
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Solution Overview
Problem
Current treatments for chronic obstructive pulmonary disease (COPD) and asthma, such as beta-2 adrenergic receptor agonists and anticholinergic bronchodilators, have limitations in providing sustained bronchodilation and require multiple daily doses, while inhaled corticosteroids may have side effects.
Innovation Solution
A novel pharmaceutical combination of 4-{(1 R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol triphenylacetate and 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide, potentially administered once daily, which acts as a muscarinic receptor antagonist and beta-2 adrenoreceptor agonist, respectively, to provide sustained bronchodilation and reduce symptoms of COPD and asthma.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If beta-2 adrenergic receptor agonists and anticholinergic bronchodilators are used for COPD and asthma treatment, then bronchodilation effect is achieved, but multiple daily doses are required and sustained bronchodilation is not provided
Solution Approach 1:
The patent combines a long-acting beta-2 adrenergic receptor agonist (salmeterol or formoterol) with a long-acting muscarinic antagonist (tiotropium or umeclidinium) into a single fixed-dose combination inhalation powder. This merging of two separate medications into one formulation enables sustained bronchodilation lasting 24 hours or more, reducing the administration frequency from multiple daily doses to once-daily dosing while maintaining effective bronchodilation throughout the day and night
Solution Approach 2:
The fixed-dose combination product serves multiple therapeutic functions simultaneously: it provides both beta-2 agonist-mediated bronchodilation and muscarinic antagonist-mediated bronchodilation, addresses both reversible and irreversible airway obstruction components, and enables once-daily administration. This multi-functionality resolves the contradiction by making a single medication regimen capable of providing sustained 24-hour bronchodilation coverage
2Reliability
If inhaled corticosteroids are used to treat COPD and asthma, then anti-inflammatory effect is achieved, but side effects occur
Solution Approach 1:
The patent extracts the bronchodilation function from corticosteroid therapy by providing pure beta-2 agonist and muscarinic antagonist combinations that achieve sustained bronchodilation without the anti-inflammatory side effects of inhaled corticosteroids. This extraction allows clinicians to treat patients who need bronchodilation but cannot tolerate or do not require corticosteroid therapy, eliminating the harmful side effects while maintaining therapeutic efficacy
Solution Approach 2:
Instead of using inhaled corticosteroids to achieve anti-inflammatory effects (which causes side effects), the patent inverts the approach by using long-acting bronchodilators (beta-2 agonists and muscarinic antagonists) to achieve sustained airway opening. This inversion provides the desired respiratory benefit through a different mechanism that avoids corticosteroid-related side effects
3Speed
If short-acting beta-2 agonists are used for immediate relief, then rapid bronchodilation is achieved, but duration of action is insufficient
Solution Approach 1:
The patent merges short-acting and long-acting beta-2 agonist properties by using formulations containing salmeterol or formoterol, which have rapid onset similar to short-acting agonists but provide extended duration of action up to 24 hours or more. This merging resolves the contradiction by providing both the rapid relief needed for acute symptoms and the sustained bronchodilation required for maintenance therapy
4Reliability
If ipratropium bromide is used four-times-a-day for COPD treatment, then bronchodilation is achieved, but compliance is reduced due to frequent dosing
Solution Approach 1:
The patent merges four separate administrations of short-acting anticholinergics into a single once-daily dose of long-acting muscarinic antagonist (tiotropium or umeclidinium). This merging maintains the bronchodilation efficacy of frequent dosing while dramatically simplifying the dosing schedule to once daily, thereby improving patient compliance and adherence without sacrificing therapeutic effectiveness
Solution Approach 2:
The long-acting muscarinic antagonist provides continuous bronchodilation action throughout the 24-hour dosing interval, ensuring sustained therapeutic effect without the peaks and troughs associated with four-times-daily dosing. This continuity of useful action maintains reliable bronchodilation while eliminating the need for frequent administration, resolving the contradiction between efficacy and ease of operation
Data Source
AI summary
Combinations of a muscarinic acetylcholine receptor antagonist and a beta 2 agonist for inhaled administration via the nose or mouth, compositions thereof, and methods of using them are provided.