Oral Bitter Compound and PDE-5 Inhibitor Formulation for PAH
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Solution Overview
Problem
Current treatments for pulmonary hypertension (PAH) are invasive, costly, and often associated with adverse effects, highlighting the need for a non-invasive and more effective therapeutic approach.
Innovation Solution
An oral pharmaceutical formulation combining bitter compounds that are agonists of TAS2R receptors, such as denatonium benzoate, denatonium chloride, and 3-caffeoylquinic-1,5-lactone, with a PDE-5 inhibitor like sildenafil, to treat PAH.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for pulmonary hypertension are used, then treatment efficacy is achieved, but the treatments are invasive, costly, and associated with adverse effects
Solution Approach 1:
The patent combines bitter compounds (TAS2R receptor agonists) with PDE-5 inhibitors in a single oral formulation. This combination therapy achieves synergistic effects, improving treatment efficacy while allowing for lower doses of each individual component, thereby reducing adverse effects associated with higher single-agent dosing.
Solution Approach 2:
The bitter compounds act as intermediaries that activate TAS2R receptors, triggering a cascade of physiological responses including increased cAMP production and smooth muscle relaxation. This intermediary mechanism provides an alternative pathway to achieve therapeutic effects without relying solely on high-dose PDE-5 inhibitors, thus reducing adverse effects.
2Reliability
If current treatments for pulmonary hypertension are used, then treatment efficacy is achieved, but the treatments are invasive and costly
Solution Approach 1:
The patent replaces invasive mechanical delivery systems (such as intravenous infusion pumps required for prostacyclin analogues) with an oral pharmaceutical formulation. The bitter compounds and PDE-5 inhibitor are administered orally, eliminating the need for invasive catheterization and continuous infusion equipment, thereby significantly improving ease of operation.
3Reliability
If higher doses of PDE-5 inhibitors are used, then treatment efficacy is improved, but adverse effects increase
Solution Approach 1:
The patent combines bitter compounds with PDE-5 inhibitors to create a synergistic therapeutic effect. The bitter compounds activate TAS2R receptors, which independently contribute to smooth muscle relaxation and vasodilation. This combined mechanism allows for lower doses of PDE-5 inhibitors to achieve the same or better therapeutic effect, thereby reducing adverse effects such as headache, flushing, and hypotension.
Solution Approach 2:
The patent changes the dosing parameters of PDE-5 inhibitors by combining them with bitter compounds. This parameter change allows for reduced PDE-5 inhibitor dosage while maintaining or improving treatment efficacy, directly addressing the contradiction between efficacy and adverse effects.
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
The combination of bitter compounds and PDE-5 inhibitors demonstrates synergistic effects in relaxing pulmonary vascular smooth muscle cells, allowing for lower doses of PDE-5 inhibitors and potentially reducing adverse effects while improving treatment efficacy.
Implementation Method 1
bitter compounds that are agonists of TAS2R receptors
Implementation Method 2
Prostacyclin serves as a brake to excessive mitogenesis of vascular smooth muscle cells acting to augment cAMP generation
Implementation Method 3
selective inhibitors of phosphodiesterase-5 (PDE5)
Implementation Method 4
the selective PDE5 inhibitor sildenafil was demonstrated to improve pulmonary hemodynamics
Implementation Method 5
The combination of bitter compounds and PDE-5 inhibitors demonstrates synergistic effects in relaxing pulmonary vascular smooth muscle cells
Data Source
AI summary
There is disclosed an oral pharmaceutical formulation of bitter compounds that are agonists of TAS2R receptors for the treatment of pulmonary hypertension (PAH). More specifically, there is disclosed a PAH oral formulation comprising a bitter agent selected from the group consisting of 3-caffeoylquinic-1,5-lactone (3-CQL), chlorogenic acid (CGA), denatonium benzoate (DB), denatonium chloride (DC), denatonium saccharide (DS), denatonium acetate (DA), and combinations thereof and a PDE-5 inhibitor.