Synergistic NO and H2S Precursor Composition for Endothelial Glycocalyx Repair

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Solution Overview

Problem

Endothelial dysfunction (ED) is a major contributor to cardiovascular diseases due to impaired nitric oxide (NO) production and increased oxidative stress, with existing therapies failing to effectively address the underlying issues of NO biosynthesis and endothelial glycocalyx damage.

Innovation Solution

A therapeutic composition combining a nitric oxide precursor and a hydrogen sulfide precursor, along with antioxidants and endothelial glycocalyx regenerating compounds, is administered to restore and sustain optimal NO levels, enhance endothelial function, and counteract oxidative stress.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapies are used to treat endothelial dysfunction, then some symptoms may be temporarily relieved, but they fail to effectively address the underlying issues of NO biosynthesis and endothelial glycocalyx damage, resulting in short-lasting effects

Engineering Contradiction:

Improveeffectiveness of therapyVSAvoidduration of therapeutic effect

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent combines multiple therapeutic agents into a single composition: an L-arginine precursor (substrate for NO synthesis), an eNOS activating compound (to enhance enzymatic activity), and an endothelial glycocalyx regenerating compound (to repair structural damage). This synergistic combination addresses multiple underlying mechanisms simultaneously, producing long-lasting therapeutic effects that extend beyond 24 hours.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The composition works by preliminarily restoring the endothelial glycocalyx structure and enhancing eNOS enzyme activity before significant NO depletion occurs. By pre-establishing the functional capacity of the endothelium through glycocalyx regeneration and enzyme activation, the system ensures sustained NO production capability that lasts beyond the immediate presence of the administered compounds.

Inventive Principle:

Principle #10Preliminary action

2Adaptability or versatility

If multiple separate therapies are administered to target different aspects of endothelial dysfunction, then comprehensive coverage is achieved, but treatment complexity increases

Engineering Contradiction:

Improvecomprehensive coverage of therapeutic targetsVSAvoidtreatment complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent integrates three distinct therapeutic agents targeting different mechanisms into a single multi-component composition: L-arginine precursor (substrate supply), eNOS activating compound (enzyme activation), and endothelial glycocalyx regenerating compound (structural repair). This unified formulation provides comprehensive coverage of endothelial dysfunction pathways while simplifying administration to a single oral dose.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The therapeutic composition serves multiple functions simultaneously: it provides substrate for NO synthesis, activates the synthetic enzyme, repairs the protective glycocalyx layer, and sustains endothelial function. This multi-functional approach allows a single treatment to address various aspects of endothelial dysfunction without requiring multiple separate therapies.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 composition effectively increases bioavailable NO, improves endothelial function, and reduces blood pressure, providing a long-lasting therapeutic effect by sustaining NO bioavailability for at least 24 hours and improving vascular health.

Implementation Method 1

administering to the subject a combination of a nitric oxide (NO) precursor and a hydrogen sulfide (H2S) precursor in an amount and at a frequency sufficient to restore and sustain an optimal or improved NO level

Methodology Applied

Scientific EffectNitric oxide synthesis: Chemical Bonding

Implementation Method 2

one or more antioxidants to deactivate superoxide and its downstream ROS to increase NO availability

Methodology Applied

Scientific EffectOxidation-reduction reaction: Redox Reactions

Implementation Method 3

an endothelial glycocalyx regenerating compound (eGRC) to repair and restore EGX to support optimal or improved NO synthesis by endothelial nitric oxide synthase (eNOS)

Methodology Applied

Scientific EffectBiological regeneration:

Data Source

PatentUS20220331353A1Synergistic compositions and methods to increase vascular nitric oxide to treat endothelial dysfunction and related conditions

Publication Date: 2022.10.20 CALROY HEALTH SCIENCES LLC

AI summary

A method of treating endothelial dysfunction in a subject can include: identifying damage in an endothelial glycocalyx (EGX) of the subject, and administering to the subject a combination of a nitric oxide (NO) precursor and a hydrogen sulfide (H2S) precursor in an amount and at a frequency sufficient to stabilize and reverse damage in the EGX.A therapeutic composition for treating endothelial dysfunction can include a combination of a nitric oxide (NO) precursor and a hydrogen sulfide (H2S) precursor in an amount sufficient to sustain an increase of bioavailable NO for the treatment of endothelial dysfunction, and a pharmaceutically acceptable carrier.