PDE5 Inhibitor and NO-Releasing Compound Combination for Pulmonary Hypertension
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Solution Overview
Problem
Current treatments for pulmonary hypertension are inadequate, leading to short life expectancy and fatal complications due to elevated pulmonary arterial pressure and associated conditions such as pulmonary edema and heart failure, with limited effective therapies available, especially for idiopathic and neonatal cases.
Innovation Solution
Administering a therapeutically effective amount of a PDE5 inhibitor, such as vardenafil, in combination with an NO-releasing compound like sodium nitrite, to induce vasodilation and reduce pulmonary arterial pressure through inhalation, either simultaneously or sequentially, to extend the half-life of the NO-releasing compound and enhance bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for pulmonary hypertension are used, then pulmonary arterial pressure is reduced, but life expectancy remains short and fatal complications occur due to inadequate treatment effectiveness
Solution Approach 1:
The patent combines a PDE5 inhibitor and an NO-releasing compound into a single therapeutic regimen for pulmonary hypertension. This combination therapy addresses the inadequacy of current monotherapies by simultaneously targeting two different mechanisms: PDE5 inhibition prevents cGMP breakdown while NO release promotes vasodilation, creating a synergistic effect that improves treatment reliability and potentially extends life expectancy in patients with inadequate response to existing therapies
2Productivity
If pulmonary arterial pressure is reduced through current therapies, then blood flow improves, but pulmonary edema and heart failure complications still occur
Solution Approach 1:
The patent changes the pharmacological parameters of pulmonary hypertension treatment by introducing a dual-mechanism approach. The PDE5 inhibitor increases cGMP levels to promote smooth muscle relaxation, while the NO-releasing compound directly donates nitric oxide to enhance vasodilation. This parameter change in therapeutic strategy aims to achieve more complete pressure reduction and blood flow improvement without the harmful complications of pulmonary edema and heart failure that occur with current therapies
3Duration of action of moving object
If NO-releasing compounds are administered alone, then vasodilation occurs, but the half-life is short and bioavailability is limited
Solution Approach 1:
The patent uses the PDE5 inhibitor as an intermediary to protect and extend the action of the NO-releasing compound. By inhibiting PDE5, the enzyme that breaks down cGMP, the inhibitor creates a protective effect that prolongs the half-life of the NO-releasing compound and enhances its bioavailability. This intermediary mechanism allows the NO compound to remain active longer and at higher effective concentrations, overcoming the limitations of short half-life and limited bioavailability when administered alone
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 PDE5 inhibitors and NO-releasing compounds effectively decreases blood pressure, increases blood flow, and induces vasodilation, thereby treating pulmonary hypertension by maintaining normal pulmonary pressures and improving lung function, potentially extending life expectancy and reducing fatal complications.
Implementation Method 1
phosphodiesterase type-5 (PDE5) inhibitor
Implementation Method 2
nitric oxide (NO)-releasing compound
Data Source
AI summary
The present disclosure provides compositions and methods for treating pulmonary hypertension. The compositions and methods are based on administering a NO-releasing compound, such as nitrite, to a subject in need thereof in an amount sufficient to increase the level of circulating nitric oxide (NO), a potent vasodilator, thereby reducing the subject's blood pressure and increasing blood flow.