Polyamine Derivative Salts for Multi-PAMP Antagonism in Sepsis

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Solution Overview

Problem

Current treatments for sepsis are inadequate as they primarily target individual pathogen-associated molecular patterns (PAMPs), failing to comprehensively address the diverse sources of PAMPs that trigger systemic inflammatory responses.

Innovation Solution

Development of medicinal salts of polyamine derivatives that effectively antagonize multiple PAMPs such as LPS, CpG DNA, PGN, LTA, virus RNA, and zymosan, formed through a specific chemical combination with pharmaceutically acceptable acids, which can be used to treat sepsis caused by both gram-negative and gram-positive bacteria.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If current antibiotics and critical medical technology are used, then treatment of sepsis is provided, but the treatment is inadequate and fails to comprehensively address diverse PAMP sources

Engineering Contradiction:
Improveability to antagonize multiple PAMPsVSAvoideffectiveness in curing sepsis
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent develops polyamine derivative medicinal salts that can simultaneously antagonize multiple types of PAMPs including LPS, CpG DNA, PGN, LTA, virus RNA, and zymosan. This multi-functional capability allows a single drug to address diverse sources of systemic inflammatory response, resolving the contradiction between versatility and effectiveness in sepsis treatment

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

2Adaptability or versatility

If existing drugs targeting individual PAMPs are used, then specific PAMP antagonism is achieved, but comprehensive sepsis treatment is difficult to accomplish

Engineering Contradiction:
Improvescope of PAMP antagonismVSAvoidtreatment regimen complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent merges multiple PAMP antagonistic activities into a single polyamine derivative medicinal salt compound. Instead of requiring separate drugs for different PAMPs, the invention combines LPS, CpG DNA, PGN, LTA, virus RNA, and zymosan antagonism into one agent, simplifying the treatment regimen while expanding the scope of PAMP coverage

Inventive Principle:
Principle #5Merging (Combining)

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 polyamine derivative medicinal salts demonstrate significant inhibition of inflammatory mediator release and improve survival rates in mouse models challenged with various bacteria, offering a broader antagonistic effect compared to existing treatments.

Implementation Method 1

the polyamine derivatives have structure of general formula 1... can effectively antagonize various PAMP such as LPS, CpG DNA, PGN, LTA, virus RNA and zymosan or the like at the same time

Methodology Applied
Scientific EffectAntagonism: Absorption (physical)

Data Source

PatentEP3369725B1Polyamine derivative medicinal salt and preparation method and use
Publication Date: 2020.10.07 GRAND PHARMA (CHINA) CO LTD
  • EP3369725B1 patent drawingFigure 1
  • EP3369725B1 patent drawingFigure 2A~2G
  • EP3369725B1 patent drawingFigure 3A~3B

AI summary

The invention relates to a kind of medicinal salts of polyamine derivatives , preparation method and use thereof in preparation of a drug for treating sepsis. These novel compounds have good antagonistic action on a plurality of pathogen-associated molecular patterns that induce sepsis, such as bacterial lipopolysacchride (endotoxin), bacterial genomic DNA, peptidoglycan, lipoteichoic acid, virus RNA, and zymosan, and can be used for preparation of a drug for treating sepsis.