Elastin Stabilization via Phenolic Compounds for Aneurysm Prevention

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Solution Overview

Problem

Current treatments for aneurysms and other conditions involving enzymatic degradation of structural proteins are invasive, risky, and may not provide a permanent solution, as they often rely on surgical interventions that carry complications and are not effective in all cases, particularly for deep-seated aneurysms.

Innovation Solution

The use of phenolic compounds, such as tannic acid and its derivatives, to stabilize connective tissue by inhibiting elastase and matrix metalloproteinase-mediated degradation of elastin, either through direct application or delivery via drug vehicles like sustained release systems, stents, or hydrogels, to prevent structural breakdown in blood vessels and other tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If invasive surgical techniques (stent graft repair or vascular graft replacement) are used to treat aneurysms, then life-saving treatment is achieved, but surgical complications and device-related complications occur

Engineering Contradiction:
Improveaneurysm treatment effectivenessVSAvoidsurgical complications and device-related complications
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Phenolic compounds serve as chemical intermediaries that mediate between the vascular tissue and the stabilizing effect. These compounds are applied topically or delivered via drug-eluting devices to provide elastin stabilization without requiring invasive surgical replacement, thereby reducing surgical complications while maintaining treatment effectiveness

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention replaces mechanical surgical interventions (stent grafts, vascular grafts) with a chemical/biological approach using phenolic compounds that stabilize elastin through molecular interactions. This substitution eliminates device-related complications such as thrombosis, leakage, and device failure while achieving the same structural stabilization goal

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Strength

If complete replacement of diseased vessel with vascular graft is performed, then structural integrity is restored, but graft loosening and dislodgment may occur over time

Engineering Contradiction:
Improvevascular structural integrityVSAvoidlong-term graft stability
Core Design Contradiction:
StrengthVSDuration of action of stationary object

Solution Approach 1:

Phenolic compounds are applied preliminarily to stabilize and preserve native elastin before complete degradation occurs. This preliminary stabilization prevents the need for graft replacement and ensures long-term stability of the native vessel structure, avoiding graft loosening and dislodgment issues

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention changes the chemical parameters of elastin through phenolic compound treatment, modifying its susceptibility to enzymatic degradation. This parameter change (reduced degradability) ensures long-term structural integrity without requiring external grafts that may loosen over time

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If phenolic compounds are applied to stabilize elastin, then elastin degradation is inhibited and tissue durability is improved, but the complexity of treatment protocol increases

Engineering Contradiction:
Improveelastin structural stabilityVSAvoidtreatment protocol complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

Phenolic compounds enable self-service stabilization where the treated tissue maintains its own structural integrity through enhanced elastin stability. The compounds work autonomously to prevent degradation without requiring complex external support systems, simplifying the overall treatment approach while maintaining stability

Inventive Principle:
Principle #25Self-service

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 effectively stabilizes elastin in connective tissue, reducing the risk of aneurysm progression and improving tissue durability, as demonstrated by significant reduction in elastin degradation and aneurysm growth, with phenolic compounds like tannic acid and pentagalloylglucose showing promise in preclinical models.

Implementation Method 1

the phenolic compound may inhibit degradation of the elastin mediated by one or more elastases; the phenolic compound may inhibit degradation of the elastin mediated by one or more matrix metalloproteinases

Methodology Applied
Scientific EffectEnzyme inhibition: Enzyme

Implementation Method 2

the phenolic compound comprises a hydrophobic core and at least one phenolic group joined to the hydrophobic core

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 3

at least one phenolic group joined to the hydrophobic core

Methodology Applied
Scientific EffectHydrogen bonding: Chemical Bonding

Data Source

PatentEP2460525B8Elastin stabilization of connective tissue
Publication Date: 2016.09.14 CLEMSON UNIV RES FOUND

AI summary

A method and product are provided for the treatment of connective tissue weakened due to destruction of tissue architecture, and in particular due to elastin degradation. The treatment agents employ certain unique properties of phenolic compounds to develop a protocol for reducing elastin degradation, such as that occurring during aneurysm formation in vasculature. According to the invention, elastin can be stabilized in vivo and destruction of connective tissue, such as that leading to life-threatening aneurysms in vasculature, can be tempered or halted all together. The treatment agents can be delivered or administered acutely or chronically according to various delivery methods, including sustained release methods incorporating perivascular or endovascular patches, use of microsphere carriers, hydrogels, or osmotic pumps