Oleanolic Acid Acetate Composition for TLR and IL-6 Pathway Inhibition

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Solution Overview

Problem

Current treatments for TLR- and IL-6-mediated diseases, such as inflammatory and autoimmune conditions, are inadequate as antioxidants do not effectively address these conditions, and existing compounds do not inhibit the NF-κB and STAT3 signaling pathways effectively.

Innovation Solution

A pharmaceutical composition containing oleanolic acid acetate or its pharmaceutically acceptable salt, derived from adzuki bean extracts, which inhibits TLR-3 and TLR-7 activation, blocks NF-κB signaling, and suppresses STAT3 phosphorylation, thereby preventing or treating TLR- and IL-6-mediated diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antioxidants are used for treating TLR- and IL-6-mediated diseases, then general oxidative stress is addressed, but they fail to effectively inhibit the NF-κB and STAT3 signaling pathways

Engineering Contradiction:
Improveeffectiveness in treating TLR- and IL-6-mediated diseasesVSAvoidability to address specific signaling pathways
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the chemical parameter from conventional antioxidants to oleanolic acid acetate, which has specific chemical structure characteristics (triterpenoid structure with acetate group) that enable it to selectively inhibit NF-κB and STAT3 signaling pathways while maintaining antioxidant properties. This parameter change resolves the contradiction by providing both pathway-specific inhibition and broad disease applicability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes oleanolic acid acetate as a composite natural compound derived from adzuki bean, combining multiple functional groups (triterpenoid core, acetate substituent, hydroxyl groups) that work synergistically to inhibit multiple signaling pathways (NF-κB, STAT3, TLR-3, TLR-7) simultaneously, thereby addressing both specificity and versatility requirements.

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If existing compounds are used to inhibit inflammatory responses, then general inflammation is reduced, but they do not effectively block TLR-3 and TLR-7 activation or NF-κB signaling

Engineering Contradiction:
Improveinflammatory cytokine productionVSAvoidinhibition of specific signaling pathways
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

Oleanolic acid acetate acts as an intermediary substance that binds to key components in the TLR-NF-κB and IL-6-STAT3 signaling cascades, blocking the transmission of inflammatory signals at multiple points including TLR-3/7 activation, MyD88/IRAK complex formation, and STAT3 phosphorylation, thereby reliably inhibiting inflammatory cytokine production.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs oleanolic acid acetate with specific chemical parameters (triterpenoid structure, acetate group at C-3 position, hydroxyl groups at C-16 and C-28) that enable it to interact with and inhibit specific signaling pathway components, providing reliable pathway-specific inhibition while reducing harmful inflammatory factors.

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If broad-spectrum anti-inflammatory agents are used, then multiple inflammatory conditions are addressed, but they lack specificity for TLR- and IL-6-mediated diseases

Engineering Contradiction:
Improveapplicability to multiple inflammatory conditionsVSAvoidspecificity for TLR- and IL-6-mediated diseases
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

Oleanolic acid acetate exhibits multi-functionality by simultaneously targeting multiple signaling pathways (TLR-3, TLR-7, NF-κB, STAT3, IL-6) that are involved in various TLR- and IL-6-mediated diseases including atopic dermatitis, rheumatoid arthritis, and metabolic disorders, thereby providing both versatility and disease-specific reliability.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The complex natural compound oleanolic acid acetate contains multiple functional moieties (triterpenoid nucleus, acetate group, hydroxyl groups) that can interact with different targets in the inflammatory signaling pathways, enabling it to address multiple inflammatory conditions with specific action on TLR- and IL-6-mediated diseases.

Inventive Principle:
Principle #40Composite materials

Data Source

PatentEP2823819B1Oleanolic acid acetate as an active ingredient for preventing or treating TLR- or il-6-mediated diseases
Publication Date: 2021.06.02 KOREA RES INST OF BIOSCIENCE & BIOTECHNOLOGY
  • EP2823819B1 patent drawingFigure 1a
  • EP2823819B1 patent drawingFigure 1b
  • EP2823819B1 patent drawingFigure 2a~2b

AI summary

The present invention relates to a pharmaceutical composition including oleanolic acid acetate or a pharmaceutically acceptable salt thereof as an active ingredient for preventing or treating TLR- and IL-6-mediated diseases, and a pharmaceutical composition including an adzuki bean extract containing the compound or the salt thereof, or a fraction thereof as an active ingredient for preventing or treating TLR- and IL-6-mediated diseases. The adzuki bean extract or the compound of the present invention is derived from a natural resource that has been used as a natural medicine for a long time, and it inhibits TLR-3 and TLR-7 activations induced by Poly(I:C) and Poly(I) which are synthetic analogues of dsRNA and ssRNA, blocks NF-κB-including signal transduction pathways, and inhibits transcriptional activation and phosphorylation of IL-6-activated inflammatory transcription factor STAT3 without causing side effects, thereby being widely used for the development of prophylactic or therapeutic agents for TLR-and IL-6-mediated diseases, for example, atopic dermatitis or arthritis.