DHEAS Alkanoyl Esters for Low-Toxicity Atherosclerosis Treatment

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Solution Overview

Problem

Current pharmacological treatments for atherosclerosis and calcific aortic valve disease (CAVD) are limited, and existing steroids like DHEA and DHEAS have shown toxicity and no significant positive effect, while sex steroids and cortisol can induce undesirable endocrinological effects.

Innovation Solution

Development of a narrow range of alkanoyl esters of DHEAS, specifically 17-lauroyloxy-5-androstene-3-sulphate, which prevent and treat atherosclerotic plaque formation and calcification by modulating H2S biosynthesis and reducing oxidative stress.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If DHEA or DHEAS is administered to treat atherosclerosis, then antioxidant effect is improved, but toxicity increases and actual positive effect is not achieved

Engineering Contradiction:
Improvetherapeutic effectVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of DHEA/DHEAS by introducing specific substituents at defined positions on the steroid nucleus, transforming the molecule into a derivative that retains antioxidant properties while eliminating toxic effects and endocrinological activity. This structural parameter change resolves the contradiction between therapeutic effect and toxicity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention extracts and isolates the beneficial antioxidant function from the parent DHEA/DHEAS molecule by creating a derivative structure that specifically targets oxidative stress pathways involved in atherosclerosis while removing the capacity to cause toxicity or hormonal effects.

Inventive Principle:
Principle #2Taking out (Extraction)

2Reliability

If sex steroids or cortisol are used to reduce superoxide anion release, then antioxidant effect is improved, but endocrinological effects are induced

Engineering Contradiction:
Improveantioxidant effectVSAvoidendocrinological effects
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful endocrinological activity of sex steroids and cortisol into a beneficial property by designing a steroid derivative that is structurally modified to be inactive at hormonal receptors while maintaining antioxidant capacity. The molecule becomes beneficial precisely because it lacks the harmful endocrinological effects of its parent compounds.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

By changing the chemical structure parameters of the steroid molecule (adding specific substituents), the invention creates a compound that selectively preserves antioxidant function while eliminating endocrinological activity, thus resolving the contradiction between therapeutic benefit and harmful side effects.

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If a narrow range of alkanoyl esters of DHEAS is developed, then selectivity for atherosclerosis treatment is improved, but device complexity increases

Engineering Contradiction:
ImproveselectivityVSAvoidmolecular structure complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies local quality by introducing specific substituents at defined positions on the steroid nucleus, creating a molecule with localized functional modifications that confer selectivity for atherosclerosis treatment while maintaining overall structural coherence and manageable complexity.

Inventive Principle:
Principle #3Local quality

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 alkanoyl esters of DHEAS effectively prevent and reverse atherosclerosis and valvular calcification, reducing reactive oxygen species and minimizing toxicity, offering a novel therapeutic approach.

Implementation Method 1

modulating H2S biosynthesis and reducing oxidative stress

Methodology Applied
Scientific EffectH2S biosynthesis:

Implementation Method 2

reducing reactive oxygen species and minimizing toxicity

Methodology Applied
Scientific EffectOxidative stress reduction: Oxidation

Data Source

PatentEP4479412B1DHEA-derived steroids
Publication Date: 2025.12.10 DEBRECENI EGYETEM
  • EP4479412B1 patent drawingFigure 1A~1B
  • EP4479412B1 patent drawingFigure 2A~2B
  • EP4479412B1 patent drawingFigure 3

AI summary

The invention relates to novel steroids derived from DHEA of formula (I), as well as their use against arteriosclerosis and/or atherosclerosis. Furthermore, the invention relates to pharmaceutical compositions and medical uses thereof. wherein R1 is C7-C13 alkyl.