Diallyl Disulfide Nitrite Conversion for CLI Diagnosis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current technologies lack strong biocompatible agents to efficiently stimulate nitrite reduction to nitric oxide, which is crucial for therapeutic applications, and face challenges in accurately diagnosing and treating conditions like critical limb ischemia versus peripheral artery disease.
Innovation Solution
The use of diallyl disulfide (DADS) and diallyl trisulfide (DATS) to selectively stimulate nitrite conversion to nitric oxide, along with diagnostic methods involving hydrogen sulfide and nitric oxide plasma levels to differentiate between critical limb ischemia and peripheral artery disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If ascorbic acid is used to facilitate nitrite reduction, then nitrite conversion to nitric oxide is enhanced, but the effect is weak and insufficient for therapeutic applications
Solution Approach 1:
The patent changes the chemical parameters by introducing compounds with different molecular structures (diallyl disulfide, diallyl trisulfide, allyl isothiocyanate) that have higher reactivity toward nitrite reduction compared to ascorbic acid, thereby achieving both high conversion efficiency and therapeutic effectiveness
Solution Approach 2:
The patent employs composite chemical formulations combining organosulfur compounds with nitrite, creating a synergistic system where the organosulfur compound acts as a catalyst or enhancer that dramatically accelerates nitrite reduction while maintaining biocompatibility
2Productivity
If strong agents are used to stimulate nitrite reduction, then conversion efficiency increases, but biocompatibility is compromised
Solution Approach 1:
The patent uses organosulfur compounds that are naturally occurring, biodegradable, and metabolized by the body into harmless substances (such as hydrogen sulfide and sulfur-containing compounds), allowing for strong nitrite reduction activity without long-term toxic accumulation
Solution Approach 2:
The patent converts potentially harmful reactive sulfur compounds into beneficial therapeutic effects by utilizing the body's natural metabolic pathways that transform these compounds into signaling molecules like hydrogen sulfide, which has its own therapeutic benefits at controlled concentrations
3Measurement precision
If nitrite levels are measured directly, then accurate diagnosis is achieved, but measurement difficulty increases due to technical challenges
Solution Approach 1:
The patent introduces diallyl disulfide as an intermediary reagent that reacts with nitrite to form a detectable product, enabling indirect measurement of nitrite levels through a simplified analytical procedure that avoids the technical difficulties of direct nitrite detection
Solution Approach 2:
The patent replaces complex instrumental measurement methods with a chemical reaction-based detection system that produces a measurable signal (such as color change or fluorescence) through the interaction between the organosulfur compound and nitrite, simplifying the measurement process
4Measurement precision
If clinical diagnosis methods like ankle brachial index are used, then basic disease identification is achieved, but differentiation between critical limb ischemia and peripheral artery disease remains limited
Solution Approach 1:
The patent measures specific local biochemical parameters (nitrite, hydrogen sulfide, and their ratios) in plasma samples, providing localized diagnostic information that reveals the underlying biochemical mechanisms distinguishing CLI from PAD, thereby recovering lost diagnostic detail
Solution Approach 2:
Instead of relying on hemodynamic measurements alone, the patent inverts the diagnostic approach by measuring biochemical markers (nitrite and hydrogen sulfide levels) that reflect the molecular mechanisms of disease pathophysiology, providing complementary information that enhances differentiation accuracy
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
DADS and DATS provide a strong and biocompatible means to increase nitric oxide levels, aiding in the treatment of conditions like inflammation and wound healing, while diagnostic methods improve the accuracy of distinguishing between CLI and PAD, enabling targeted therapies.
Implementation Method 1
the biochemical mechanism of nitrite reduction to NO, and thereby increasing NO levels, is poorly understood. Nitrite reduction in vivo occurs through different pathways
Implementation Method 2
Some agents can facilitate such reduction, such as ascorbic acid, but do so weakly. Strong biocompatible agents to stimulate nitrite reduction to NO are not available in current technology
Data Source
AI summary
Methods and therapeutics for treating nitric oxide (NO) mediated condition comprising administering a therapeutically effective amount of a pharmaceutical composition containing a therapeutic, wherein the therapeutic one of increases xanthine oxidase (XO) associated nitrite conversion to nitric oxide and increases nitrite conversion to nitric oxide via DADS. Method and devices for measuring an amount of nitrite in a sample comprising obtaining a sample, adding diallyl disulfide (DADS) to the sample, measuring a post DADS amount of nitric oxide (NO) in the sample, and using the post DADS amount of NO in the sample to determine the amount of nitrite in the sample. Methods and therapeutics for diagnosing and treating critical limb ischemia (CLI) versus non-critical limb ischemic peripheral artery disease (PAD) in a patient comprising determining a patient indicator value, where the patient indicator is value one of a total hydrogen sulfide metabolite plasma level, a total nitric oxide, nitrite, and nitrite (NOx) plasma level, a ratio of free hydrogen sulfide plasma level to total NOx plasma level, and a ratio of total hydrogen sulfide metabolite plasma level and total NOx plasma level, diagnosing the patient with as having CLI based on the patient indicator value, and administering to the patient a therapeutic for CLI.