Gap Junction Enhancing Agents for Intestinal Mucosal Healing

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Solution Overview

Problem

Necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD) are characterized by impaired gap junctions between enterocytes, leading to impaired enterocyte migration, mucosal defects, and severe inflammation, with current treatments lacking specific therapies.

Innovation Solution

Administration of gap junction enhancing agents, such as peptides and peptide analogs, to increase gap junction functionality between enterocytes, promoting their migration and reducing intestinal inflammation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If gap junction functionality between enterocytes is impaired, then intestinal inflammation severity increases, but enterocyte migration rate decreases

Engineering Contradiction:

Improveenterocyte migration rateVSAvoidintestinal inflammation severity

Core Design Contradiction:

SpeedVSObject-affected harmful factors

Solution Approach 1:

The patent uses gap junction enhancing agents to modify the functional state of gap junction channels, changing the parameter of intercellular communication efficiency. This restores enterocyte migration rate while simultaneously reducing inflammation severity by improving coordinated cellular movement and barrier function.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If broad spectrum antibiotics and surgical removal are used for NEC treatment, then mortality is reduced, but specific therapeutic needs are not met and long term complications occur

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidlong term complications

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and targets the specific underlying mechanism of NEC (impaired gap junction function) rather than treating all symptoms with broad-spectrum antibiotics. By specifically enhancing gap junction functionality, the treatment addresses the root cause while avoiding the harmful side effects of non-specific antibiotic therapy and surgery.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The gap junction enhancing agents act as intermediary substances that restore cellular communication and coordination. These agents mediate the therapeutic effect by improving enterocyte migration and reducing inflammation without requiring surgical intervention or broad-spectrum antibiotic treatment, thereby avoiding long-term complications.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If interferon gamma is released to fight infection, then immune response increases, but gap junction function is inhibited and mucosal healing is impaired

Engineering Contradiction:

Improveimmune response effectivenessVSAvoidenterocyte migration rate

Core Design Contradiction:

ReliabilityVSSpeed

Solution Approach 1:

The patent applies preliminary anti-action by using gap junction enhancing agents to counteract the inhibitory effect of interferon gamma on gap junction function. This restores enterocyte migration capability even in the presence of elevated interferon gamma levels, allowing mucosal healing to proceed despite the ongoing immune response.

Inventive Principle:

Principle #9Preliminary anti-action

Data Source

PatentUS10172848B2Gap junction-enhancing agents for treatment of necrotizing enterocolitis and inflammatory bowel disease

Publication Date: 2019.01.08 UNIV OF PITTSBURGH OF THE COMMONWEALTH SYST OF HIGHER EDUCATION

AI summary

The present invention relates to methods of reducing the risk of occurrence of, and/or treating, necrotizing enterocolitis (“NEC”) or inflammatory bowel disease (“IBD”) comprising administering, to a subject in need of such treatment, an effective amount of a gap junction enhancing agent (“GJEA”), for example a peptide (“GJP”) or peptide analog (“GJPA”). It is based, at least in part, on the discovery that greater functionality of gap junctions between enterocytes increases their rate of migration and reduces the severity of intestinal inflammation.