Ciclesonide Prodrug for Pediatric Asthma
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for respiratory diseases in children, particularly asthma, often result in systemic side effects such as growth suppression due to long-term exposure to inhaled and intranasal corticosteroids.
Innovation Solution
Administering ciclesonide, a novel inhaled corticosteroid, in doses ranging from 20 to 200 μg, which is readily converted to an active metabolite in the lungs, providing local anti-inflammatory activity with minimal systemic absorption, thereby reducing systemic side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If inhaled and intranasal corticosteroids are administered to children for long-term treatment of respiratory diseases, then anti-inflammatory activity is improved, but systemic side effects such as growth suppression occur
Solution Approach 1:
The patent applies local quality by designing a prodrug (ciclesonide) that is specifically activated in the lung tissue where it is needed. The compound is converted to its active form by esterases present in lung tissue, creating high local concentration of active drug at the target site while maintaining low systemic levels, thus providing effective local anti-inflammatory action with minimal systemic side effects
Solution Approach 2:
The patent uses an intermediary approach by introducing a prodrug structure that requires metabolic conversion. Ciclesonide serves as the inactive prodrug intermediary that is transported systemically but only activated in the lung tissue by local esterases, acting as a mediator between systemic administration and local therapeutic effect
2Reliability
If ciclesonide is converted to active metabolite desisobutyryl-ciclesonide in the lungs, then local anti-inflammatory activity is enhanced, but systemic absorption increases
Solution Approach 1:
The conversion of ciclesonide to desisobutyryl-ciclesonide is spatially controlled to occur primarily in lung tissue where esterases are abundant. This creates a local quality difference where the active metabolite is generated where needed (high concentration in lungs) while systemic conversion remains minimal (low concentration elsewhere), resolving the contradiction between local efficacy and systemic exposure
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Effectively treats and prevents respiratory diseases in children while minimizing systemic side effects like growth suppression, as demonstrated by clinical studies showing no significant impact on lower-leg growth rates or HPA-axis function.
Implementation Method 1
This activation occurs by ester cleavage at the C21 position of ciclesonide
Implementation Method 2
Ciclesonide is only moderately absorbed after oral administration and has low systemic activity
Data Source
AI summary
The invention relates to new method of treatment of respiratory diseases, in particular the treatment of asthmatic children.