GTN Granules with Ester Stabilizer for Arteriogenesis
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Solution Overview
Problem
Current treatments for arterial insufficiency, such as nitroglycerin, do not effectively induce arteriogenesis or improve the underlying condition, instead only providing acute relief for symptoms like angina pectoris, and there is a need for agents that can promote collateral circulation to address the underlying issue of arterial occlusion.
Innovation Solution
Administration of a nitric oxide donor, specifically glyceryl trinitrate in a solid pharmaceutical preparation with a non-volatile ester stabilizer, in an intermittent manner to induce arteriogenesis, which includes a preparation containing between 0.05 and 2 weight % GTN, a diluent, a carrier material, and a non-volatile ester stabilizer with a melting point not higher than 60°C, to promote collateral circulation and treat arterial insufficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If nitroglycerin is administered continuously, then vasodilating effect is maintained, but arteriogenesis is not induced
Solution Approach 1:
The patent applies periodic action by administering nitroglycerin in intermittent doses rather than continuously. The formulation is designed to release nitroglycerin over extended periods (weeks to months) with pulsatile or intermittent release patterns, which induces arteriogenesis while maintaining adequate vasodilating effect during active phases. This periodic administration strategy resolves the contradiction by showing that continuous administration fails to induce arteriogenesis, while intermittent administration successfully promotes collateral vessel formation.
2Power
If nitroglycerin is administered in high concentrations, then vasodilating effect is enhanced, but stability and shelf life are reduced
Solution Approach 1:
The patent applies parameter changes by modifying the physical state and concentration parameters of nitroglycerin in the formulation. Nitroglycerin is incorporated at low concentrations (0.01-5% w/w) into a solid carrier matrix, changing its physical state from liquid to solid-bound form. This parameter change maintains adequate vasodilating effect through controlled release while dramatically improving stability and shelf life by preventing degradation and volatility issues associated with high concentrations.
Solution Approach 2:
The patent uses a carrier material (such as lactose, sucrose, or other pharmaceutically acceptable solids) as an intermediary substance. This carrier acts as a mediator that holds the nitroglycerin in a stable, non-volatile form while allowing controlled release into the bloodstream. The carrier material protects nitroglycerin from degradation and maintains shelf life, while still enabling the drug to exert its vasodilating and arteriogenic effects when administered.
3Stability of the object's composition
If nitroglycerin is formulated as a solid preparation, then stability and shelf life are improved, but volatility control becomes challenging
Solution Approach 1:
The patent employs a solid carrier matrix that acts as a protective shell or matrix structure. This solid formulation creates a physical barrier that confines nitroglycerin molecules, preventing their volatilization while maintaining stability. The carrier material forms a structured environment that holds nitroglycerin in place, preventing escape into the atmosphere, while still allowing controlled release when the formulation is administered to the patient.
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 intermittent administration of the NO donor effectively induces arteriogenesis, providing a tool for both treating and preventing arterial insufficiency by improving blood and oxygen supply to tissues, reducing symptoms, and potentially reducing infarct size and arrhythmias, while maintaining stability and prolonged shelf life of the pharmaceutical preparation.
Implementation Method 1
at least one substance that reduces the volatility of GTN, whereby this substance is a non-volatile ester stabilizer
Data Source
AI summary
The present invention inter alia relates to a method of treating or preventing an arterial insufficiency, wherein an NO donor is administered in an intermitting manner to a subject in an amount effective for the induction of arteriogenesis, and wherein the NO donor is a solid pharmaceutical preparation with the active substance glyceryl trinitrate for oromucosal or oral administration characterized in that it contains between 0.05 and 2 weight % glyceryl trinitrate (GTN), at least one diluent, one carrier material, and at least one substance that reduces the volatility of GTN, whereby this substance is a non-volatile ester stabilizer whose melting point is not higher than 60° C.