CFTR Modulator Composition with PEG Carrier for Ion Transport
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Solution Overview
Problem
Current treatments for CFTR-mediated diseases, such as cystic fibrosis, are inadequate, particularly for patients with residual CFTR activity, as they fail to effectively modulate CFTR activity to improve ion and fluid transport across epithelial tissues, leading to persistent respiratory and gastrointestinal issues.
Innovation Solution
Pharmaceutical compositions containing N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) are developed, combined with suitable liquid PEG and optionally a viscosity enhancing agent, to modulate CFTR activity in the cell membrane, thereby treating or lessening the severity of CFTR-mediated diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for CFTR-mediated diseases, then they are simple to administer, but they fail to effectively modulate CFTR activity to improve ion and fluid transport
Solution Approach 1:
The patent employs a composite pharmaceutical formulation consisting of Compound 1 (N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide) combined with liquid PEG (polyethylene glycol) and optionally a viscosity enhancing agent. This composite approach enhances CFTR activity modulation effectiveness while managing the complexity through careful selection of compatible excipients that work synergistically with the active compound.
2Reliability
If Compound 1 is combined with liquid PEG and viscosity enhancing agent, then CFTR activity is effectively modulated, but the formulation complexity increases
Solution Approach 1:
Liquid PEG serves as an intermediary carrier that facilitates the delivery and absorption of Compound 1. The PEG acts as a mediating substance that enhances the bioavailability and effectiveness of the active compound while managing the formulation's physical properties. The optional viscosity enhancing agent further mediates the formulation's rheological characteristics to optimize delivery.
Solution Approach 2:
The formulation utilizes parameter changes in the physical and chemical properties of the excipients to optimize drug delivery. By adjusting the molecular weight and viscosity of PEG, and selecting appropriate viscosity enhancing agents, the formulation achieves optimal balance between stability, bioavailability, and ease of administration, thereby enhancing CFTR modulation effectiveness without excessive complexity.
3Reliability
If CFTR activity is enhanced to improve ion and fluid transport, then respiratory and gastrointestinal issues are alleviated, but the treatment may have side effects
Solution Approach 1:
The patent employs Compound 1, which is a structural analog or derivative designed to replicate and enhance the desired CFTR modulating effect while improving upon the safety profile of earlier compounds. By copying and optimizing the pharmacophore features, the compound achieves effective CFTR activity modulation with reduced off-target effects and improved safety.
Data Source
AI summary
Pharmaceutical compositions including N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) and methods of using such compositions are described herein.