CFTR Potentiator-Corrector Compositions for Cystic Fibrosis Fluid Balance
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for cystic fibrosis, particularly those targeting the F508del mutation, are inadequate in improving anion transport and fluid balance, leading to severe respiratory and digestive issues, and there is a need for compounds that can reduce the severity of CFTR-mediated diseases.
Innovation Solution
The use of a pharmaceutical composition comprising 250 mg of CFTR potentiator compound N-(2-(tert-butyl)-5-hydroxy-4-(2-(methyl-d3) propan-2-yl-1,1,1,3,3,3-d6)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide, optionally combined with CFTR correctors like (14S)-8-[3-(2-{Dispiro[2.0.2.1]heptan-7-yl}ethoxy)-1H-pyrazol-1-yl]-12,12-dimethyl-226-thia-3,9,11,18,23-pentaazatetracyclo[17.3.1.111,14.05,10]tetracosa-1 (22),5,7,9,19 (23),20-hexaene-2,2,4-trione calcium salt hydrate Form D and (R)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl) cyclopropanecarboxamide, to enhance CFTR channel activity and correct protein trafficking.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current CFTR modulating compounds are used to treat cystic fibrosis, then some improvement in anion transport may be achieved, but the treatment is inadequate in improving anion transport and fluid balance
Solution Approach 1:
The patent combines multiple CFTR modulating compounds (correctors and potentiators) into a single pharmaceutical composition to achieve synergistic effects. This merging of multiple active ingredients addresses the inadequacy of single-compound treatments by simultaneously improving anion transport and fluid balance through complementary mechanisms of action.
Solution Approach 2:
The invention uses composite pharmaceutical formulations containing multiple CFTR modulators with different mechanisms. This composite approach allows the treatment to address both anion transport defects and fluid balance issues that cannot be adequately addressed by single compounds alone.
2Reliability
If higher doses of CFTR modulators are administered to improve therapeutic outcomes, then anion transport may be enhanced, but the complexity of treatment regimen increases
Solution Approach 1:
By combining multiple CFTR modulators in a single pharmaceutical composition, the patent reduces treatment complexity despite using higher total doses. The combined formulation delivers multiple active ingredients simultaneously, achieving enhanced therapeutic outcomes without requiring multiple separate administrations or complex dosing schedules.
Data Source
AI summary
This application describes methods of treating cystic fibrosis or a CFTR mediated disease comprising administering Compound I or a pharmaceutically acceptable salt thereof.The application also describes pharmaceutical compositions comprising Compound I or a pharmaceutically acceptable salt thereof and optionally comprising one or more additional CFTR modulating agents.