Ac-PGP Peptide Ligand for CXCR2 Receptor Binding in Sepsis Treatment

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Solution Overview

Problem

Current treatments for infectious and inflammatory diseases, such as sepsis, are inadequate in effectively removing bacteria, suppressing inflammatory responses, and preventing apoptosis of immune cells, leading to high mortality rates due to excessive apoptosis and uncontrolled inflammatory cytokine production.

Innovation Solution

A pharmaceutical composition containing a peptide ligand, specifically Ac-PGP, that binds to CXCR2, promoting phagocytosis, reducing inflammatory cytokine production, and suppressing apoptosis of immune cells, administered via subcutaneous injection at an effective dose of 1 to 200 mg per kg body weight.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics are used to treat bacterial infections, then bacterial infection diseases can be treated, but super bacteria are created due to abuse of antibiotics

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidsuper bacteria formation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a peptide ligand as an intermediary substance that binds to CXCR2 receptors on phagocytes, serving as a mediator between the immune system and bacteria. This peptide acts as a new type of therapeutic agent that does not directly kill bacteria like antibiotics, but rather enhances the immune system's ability to fight infections, thereby avoiding the selection pressure that leads to super bacteria formation while maintaining treatment effectiveness

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If pro-inflammatory cytokines increase to fight infection, then immune response is activated, but excessive apoptosis of lymphocytes occurs leading to organ paralysis

Engineering Contradiction:

Improveimmune response activationVSAvoidexcessive apoptosis and organ damage

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by using the peptide ligand to block excessive pro-inflammatory cytokine production before it can cause harmful effects. The peptide binds to CXCR2 receptors and prevents the downstream signaling that leads to cytokine storm and excessive apoptosis, thereby counteracting the harmful effects before they occur while still allowing necessary immune response activation

Inventive Principle:

Principle #9Preliminary anti-action

3Reliability

If CXCR2 expression is down-regulated in sepsis patients, then neutrophil activation fails, but bacterial removal efficiency decreases

Engineering Contradiction:

Improveneutrophil activationVSAvoidbacterial removal efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by using the peptide ligand to alter the functional state of CXCR2 receptors. Even when receptor expression is down-regulated, the high-affinity peptide ligand can bind to the available receptors and activate them effectively, changing the functional parameter of receptor activation to compensate for reduced expression levels and maintain bacterial removal efficiency

Inventive Principle:

Principle #35Parameter changes

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 Ac-PGP peptide ligand effectively increases survival rates, reduces bacterial load, suppresses inflammation, and inhibits apoptosis in immune cells, thereby improving treatment outcomes for sepsis and septic shock by enhancing phagocytic activity and modulating cytokine production.

Implementation Method 1

CXCR2 is a receptor for a typical chemoattractant that is found in phagocytes such as neutrophils, monocytes and macrophages. In vitro activation of CXCR2 by CXCL8 or KC induces leukocyte chemotactic movement in neutrophils and monocytes.

Methodology Applied

Scientific EffectChemotaxis:

Implementation Method 2

The active component may promote removal of bacteria by phagocytosis

Methodology Applied

Scientific EffectPhagocytosis:

Implementation Method 3

The active component may suppress an inflammatory response

Methodology Applied

Scientific EffectCytokine suppression:

Implementation Method 4

The active component may suppress apoptosis of immune cells

Methodology Applied

Scientific EffectApoptosis inhibition:

Data Source

PatentUS8937038B2Composition containing peptide ligand that bonds with CXCR2 for treating infective and inflammatory diseases

Publication Date: 2015.01.20 RES & BUSINESS FOUND SUNGKYUNKWAN UNIV

AI summary

A therapeutic agent for treating an infectious or inflammatory disease, a pharmaceutical composition for treating an infectious or inflammatory disease, and a method of using a pharmaceutical composition are provided. The pharmaceutical composition includes a peptide ligand that binds with CXCR2 as an active component. The active component can be useful in preventing and treating infectious and/or inflammatory diseases, including sepsis and septic shock by promoting the removal of bacteria by phagocytosis, suppressing an inflammatory response, and suppressing the apoptosis of immune cells.