PPARδ Agonists Modifying LDL Particle Size and Density

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Solution Overview

Problem

Current drugs fail to effectively increase LDL particle size and decrease LDL particle density, with most lipid-lowering agents, such as statins, decreasing LDL particle size and increasing density, while few drugs significantly reduce atherogenic small, dense LDL particles.

Innovation Solution

Administration of a therapeutically-effective amount of a compound, such as those in Formula I or its salts, prodrugs, or isomers, which changes LDL particle size pattern from pattern I or B to pattern A, reducing small, dense LDL particles and associated risk factors like Apolipoprotein B-100 and triglyceride levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If statins or conventional lipid-lowering agents are administered, then LDL cholesterol levels are reduced, but LDL particle size decreases and density increases, resulting in more atherogenic small dense LDL particles

Engineering Contradiction:

ImproveLDL cholesterol levelVSAvoidLDL particle size and density

Core Design Contradiction:

Quantity of substanceVSShape

Solution Approach 1:

The patent applies parameter changes by modifying the chemical structure of PPARδ agonists through various substitutions and modifications (e.g., different R groups, esterifications, amide formations) to achieve optimal balance between LDL cholesterol reduction and maintenance of LDL particle size, thereby reducing atherogenicity while lowering cholesterol levels

Inventive Principle:

Principle #35Parameter changes

2Reliability

If no specific intervention is taken, then LDL particle size and density remain unchanged, but atherogenic risk increases due to predominance of small dense LDL particles

Engineering Contradiction:

ImproveLDL particle size stabilityVSAvoidatherogenic risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses PPARδ agonists as intermediary compounds that mediate between metabolic control and LDL particle characteristics. These agonists act through the PPARδ receptor pathway to influence lipid metabolism, thereby stabilizing LDL particle size and reducing atherogenic risk through biochemical mediation rather than direct physical intervention

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS11007162B2Methods of reducing small, dense LDL particles

Publication Date: 2021.05.18 CYMABAY THERAPEUTICS INC

AI summary

The present invention provides methods for increasing LDL particle size.