Lactoferrin Modified Release Formulation for AIEC Invasion

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Solution Overview

Problem

Current treatments for inflammatory bowel diseases (IBD) associated with Adherent-invasive Escherichia coli (AIEC) invasion often result in significant side-effects due to prolonged use of antibiotics, anti-inflammatory drugs, and corticosteroids, necessitating a more effective and side-effect-free therapeutic option.

Innovation Solution

A modified release formulation comprising bovine lactoferrin, which inhibits AIEC invasion of intestinal epithelial cells without reducing inflammation, is developed, utilizing a controlled release system that ensures localized or systemic activity with immediate topical or systemic availability, preventing AIEC adhesion and internalization in a dose-dependent manner.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics, anti-inflammatory drugs and corticosteroids are used to treat IBD associated with AIEC invasion, then the infection and inflammation are reduced, but significant side-effects occur due to prolonged use

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidside-effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Lactoferrin acts as an intermediary substance that mediates the treatment of AIEC invasion. It binds to AIEC bacteria and inhibits their ability to adhere to and invade intestinal epithelial cells, while also modulating the immune response. This intermediary approach provides therapeutic effect without the direct toxicity of antibiotics or the significant side-effects of prolonged corticosteroid use

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the therapeutic parameter from conventional antibiotics and corticosteroids to lactoferrin, a natural iron-binding protein with antimicrobial and anti-inflammatory properties. This parameter change allows treatment of AIEC invasion through a different mechanism that avoids the side-effect profile of conventional medications

Inventive Principle:
Principle #35Parameter changes

2Reliability

If lactoferrin is used to prevent AIEC invasion, then AIEC adhesion and internalization are inhibited, but the formulation must ensure adequate release and availability at the site of action

Engineering Contradiction:
ImproveAIEC invasion preventionVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The formulation is designed to release lactoferrin locally at the site of AIEC invasion in the gastrointestinal tract. The modified release system ensures that lactoferrin becomes available where it is needed most - in contact with AIEC bacteria on the intestinal mucosa - providing localized therapeutic action without requiring complex systemic delivery mechanisms

Inventive Principle:
Principle #3Local quality

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 lactoferrin formulation effectively prevents AIEC invasion and reduces inflammation without cytotoxic or bactericidal effects, maintaining remission in patients with Crohn's disease and other IBDs, offering a side-effect-free treatment for chronic inflammatory conditions.

Implementation Method 1

Lactoferrin (Lf), a member of the tranferrin family of iron-binding glycoproteins

Methodology Applied
Scientific EffectIron-binding:

Implementation Method 2

Biological properties reported for Lf include antimicrobial activity against a wide range of pathogenic bacteria

Methodology Applied
Scientific EffectAntimicrobial activity:

Implementation Method 3

a modified release formulation comprising lactoferrin for use in the treatment of inflammatory bowel disease associated with Adherent-invasive Escherichia coli (AIEC) invasion

Methodology Applied
Scientific EffectControlled release:

Data Source

PatentEP3049102B1Lactoferrin for the treatment of IBD associated with bacterial invasion
Publication Date: 2020.03.04 GIELLEPI SPA
  • EP3049102B1 patent drawingFigure 1~2
  • EP3049102B1 patent drawingFigure 3A~3C
  • EP3049102B1 patent drawingFigure 4A~4B

AI summary

The present invention relates to a substance and an oral formulation for modified release dosage for use in the treatment of inflammatory bowel disease due to Escherichia coli invasion.