Nitroglycerin Dosing Protocol for Arterial Insufficiency

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Solution Overview

Problem

Short acting nitroglycerin donors used for treating cardiovascular diseases, such as angina pectoris, often cause significant side effects like headache, dizziness, and hypotension, which can lead to reduced patient compliance and treatment adherence, especially in non-emergency settings where the benefits of long-term prophylaxis are sought.

Innovation Solution

Administering nitroglycerin in a gradually increasing manner over a defined period of 3 days to 40 weeks, with doses ranging from 0.05 mg to 2.0 mg, in an intermittent fashion to mimic physiological NO release, thereby reducing side effects and promoting endothelial health.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If short acting nitroglycerin is administered at high doses for therapeutic effect, then the treatment efficacy for arterial insufficiency is improved, but side effects like headache and dizziness increase significantly

Engineering Contradiction:
Improvetreatment efficacyVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by implementing a gradual dose escalation protocol before reaching the therapeutic dose. Patients start with low doses (e.g., 0.1-0.2 mg) and incrementally increase over days to weeks, allowing the body to adapt and reduce side effects before achieving full therapeutic effect

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements periodic action through intermittent dosing schedules with drug-free intervals. Instead of continuous high-dose administration, the protocol uses periodic dosing (e.g., every other day or with specific interval patterns) that allows the body to recover and reduces cumulative side effects while maintaining therapeutic benefit

Inventive Principle:
Principle #19Periodic action

2Reliability

If short acting nitroglycerin is administered continuously to maintain therapeutic levels, then the prophylactic benefit is improved, but patient compliance deteriorates due to persistent side effects

Engineering Contradiction:
Improveprophylactic benefitVSAvoidpatient compliance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent applies periodic action by designing intermittent dosing regimens with drug-free intervals that prevent continuous exposure. This reduces side effects like headache and tolerance development, thereby improving patient compliance while maintaining sufficient prophylactic benefit through strategic timing of doses

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent implements dynamics by making the dosing regimen adaptable and flexible. The protocol allows adjustment of dose frequency and intervals based on individual patient response, tolerability, and clinical need, transforming a static continuous regimen into a dynamic personalized schedule that improves compliance

Inventive Principle:
Principle #15Dynamics

3Speed

If the dose is increased rapidly to achieve therapeutic effect, then the treatment onset is improved, but side effects become more severe and tolerance develops

Engineering Contradiction:
Improvetreatment onsetVSAvoidside effects and tolerance
Core Design Contradiction:
SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by implementing a structured gradual escalation protocol that prepares the patient's system in advance. Rather than rapid dose increases, the protocol uses predetermined incremental steps with monitoring periods, allowing physiological adaptation that prevents severe side effects and tolerance while still achieving therapeutic onset within a reasonable timeframe

Inventive Principle:
Principle #10Preliminary action

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

This approach reduces side effects like headache and dizziness, enhances patient compliance, and promotes arteriogenesis, addressing the underlying cause of arterial insufficiency by maintaining elevated NO levels for therapeutic benefits without prolonged exposure risks.

Implementation Method 1

Short acting NO donors, and especially nitroglycerin (glyceryl trinitrate, GTN), are used since decades as vasodilating agents

Methodology Applied
Scientific EffectNitric oxide release:

Data Source

PatentEP3554483B1Reducing side effects of short acting no donors
Publication Date: 2024.01.31 G POHL BOSKAMP GMBH & CO KG
  • EP3554483B1 patent drawingFigure 1
  • EP3554483B1 patent drawingFigure 2
  • EP3554483B1 patent drawing

AI summary

The present invention pertains to a short acting NO donor for use in a method of reducing side effects of a treatment with said short acting NO donor, comprising administering during a defined time period a gradually increasing amount of said short acting NO donor in an intermitting manner. The present invention is further directed to a short acting NO donor for use in a method for the prevention or treatment of an arterial insufficiency, wherein the NO donor is administered in an intermitting manner, and wherein during the initial phase of the administration, the amount of said short acting NO donor is gradually increased.