Lipid Emulsion Nitric Oxide Delivery for Pulmonary Embolism
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Solution Overview
Problem
Current methods for delivering nitric oxide (NO) are inefficient and often result in side effects such as methemoglobin formation and tolerance development, particularly in treating conditions like pulmonary embolism, where NO administration is beneficial but existing treatments do not effectively reach the lungs or systemic vessels without causing systemic vasodilation and other adverse effects.
Innovation Solution
Formulating NO in a lipid emulsion for intravenous administration, which allows NO to reach the lungs and reduce methemoglobin formation, using carriers like glycerol, carbohydrates, and polyethylene glycol that form reversible bonds with NO, enabling controlled release and avoiding enzymatic mechanisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nitric oxide is administered to treat pulmonary embolism, then vasodilatory effects and perfusion improvement are achieved, but methemoglobin formation and tolerance development occur as harmful side effects
Solution Approach 1:
The patent uses a lipid emulsion as an intermediary carrier to deliver nitric oxide. The lipid emulsion protects NO from direct contact with hemoglobin in the blood, preventing methemoglobin formation, while still allowing NO to reach the lungs and exert its therapeutic vasodilatory effects. This mediator approach resolves the contradiction by decoupling the beneficial lung-targeted effects from the harmful systemic side effects.
Solution Approach 2:
The patent changes the physical and chemical parameters of NO delivery by formulating it in a lipid emulsion rather than administering it as a gas or aqueous solution. This parameter change allows controlled release of NO, maintains lower systemic concentrations to prevent methemoglobin formation, and enables sustained therapeutic levels in the lungs without triggering tolerance development.
2Object-affected harmful factors
If nitric oxide is inhaled to treat pulmonary embolism, then lung-specific vasodilation is achieved, but the treatment is ineffective in reaching systemic vessels and providing comprehensive perfusion improvement
Solution Approach 1:
The lipid emulsion formulation of nitric oxide provides multi-functionality: it can be administered intravenously to achieve both lung-specific effects (through pulmonary artery delivery) and systemic effects (through distribution to systemic vessels). This single formulation resolves the contradiction by making the treatment versatile enough to address both localized pulmonary embolism and broader perfusion needs.
Solution Approach 2:
The lipid emulsion acts as a mediator that enables NO to traverse the bloodstream and reach multiple target sites. Unlike inhaled NO that is confined to the lungs, the lipid-emulsified NO can travel systemically while being released in a controlled manner, providing both pulmonary and systemic vasodilation to improve overall perfusion.
3Productivity
If nitric oxide is administered in high doses to ensure therapeutic effect, then perfusion improvement is enhanced, but systemic vasodilation and hypotension occur as adverse effects
Solution Approach 1:
The lipid emulsion formulation creates local quality differences in NO distribution: it concentrates NO release in the lungs (where it is most needed for embolism treatment) while maintaining lower systemic concentrations. This localized delivery enhances perfusion improvement in the pulmonary circulation without causing excessive systemic vasodilation and hypotension that would occur with high-dose systemic administration.
Solution Approach 2:
The patent changes the delivery parameters of NO by using lipid emulsion, which alters the pharmacokinetics to achieve higher local concentrations in the lungs while maintaining lower systemic concentrations. This parameter change allows therapeutic doses to be delivered without proportionally increasing systemic side effects, as the lipid carrier controls the rate and location of NO release.
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 lipid emulsion formulation significantly increases expired NO levels, protects against pulmonary embolism, and provides vasodilatory effects without significant methemoglobin formation, improving perfusion and reducing systemic side effects like hypotension.
Implementation Method 1
Formulating NO in a lipid emulsion for intravenous administration, which allows NO to reach the lungs
Implementation Method 2
using carriers like glycerol, carbohydrates, and polyethylene glycol that form reversible bonds with NO, enabling controlled release
Implementation Method 3
protects against pulmonary embolism, and provides vasodilatory effects without significant methemoglobin formation
Implementation Method 4
provides vasodilatory effects without significant methemoglobin formation, improving perfusion
Data Source
AI summary
Gaseous nitric oxide (NO) can be delivered to a mammal for prophylactic or therapeutic purposes using a composition capable of delivering NO, comprising a compound capable of forming a reversible bond or association with NO. Methods for the manufacture and use of said composition are disclosed.