Acrylonitrile Membrane Zwitterionic Coating Thrombogenicity

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Solution Overview

Problem

Current semipermeable membranes for blood treatment, such as AN69 membranes, face challenges in reducing thrombogenicity and systemic anticoagulation requirements during extracorporeal blood treatment.

Innovation Solution

The membranes are coated with a mixture of a polycationic polymer, like polyethyleneimine, and a zwitterionic compound, (2-(methacryloyl-oxy)ethyl)dimethyl(3-sulfopropyl)ammonium hydroxide, to reduce thrombogenicity and enhance the immobilization of anticoagulation agents like heparin, thereby minimizing systemic anticoagulation needs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a negatively charged semi-permeable membrane based on polyacrylonitrile is used for blood treatment, then the membrane provides effective separation and treatment of blood, but the membrane activates thrombogenicity and requires systemic anticoagulation

Engineering Contradiction:
Improveblood treatment effectivenessVSAvoidthrombogenicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

A zwitterionic compound acts as an intermediary layer on the membrane surface, creating a steric barrier that prevents direct contact between blood components and the negatively charged membrane, thereby reducing thrombogenicity while maintaining treatment effectiveness

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The zwitterionic compound is specifically applied to the blood-contacting surface of the membrane, creating a localized modification that reduces thrombogenicity at the critical interface without altering the bulk membrane properties needed for separation

Inventive Principle:
Principle #3Local quality

2Object-affected harmful factors

If a cationic polymer is incorporated into the membrane to reduce contact phase activation, then thrombogenicity is reduced, but the membrane requires additional materials and complex incorporation processes

Engineering Contradiction:
Improvecontact phase activationVSAvoidmembrane composition complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The zwitterionic compound forms a surface coating that can be applied as a thin, disposable layer, avoiding the need for complex bulk modification of the membrane structure while achieving the desired thrombogenicity reduction

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The membrane system becomes a composite structure combining the base polyacrylonitrile membrane with a zwitterionic surface layer, where each component performs its specific function: the base membrane provides separation and the surface layer provides anti-thrombogenic properties

Inventive Principle:
Principle #40Composite materials

3Quantity of substance

If an anticoagulation agent is bound to the membrane surface to reduce systemic anticoagulation, then systemic anticoagulation requirements are reduced, but the membrane structure becomes more complex with multiple coating layers

Engineering Contradiction:
Improvesystemic anticoagulation agent quantityVSAvoidmembrane coating structure
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The zwitterionic compound itself provides anticoagulant properties through its molecular structure, eliminating the need for additional anticoagulation agents while maintaining the simplified single-layer coating structure

Inventive Principle:
Principle #25Self-service

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 modified membranes exhibit reduced thrombogenicity and improved ability to immobilize anticoagulation agents, potentially allowing for heparin-free dialysis and efficient removal of uremic toxins, including middle molecules, with enhanced convective properties for extended renal replacement therapy.

Implementation Method 1

coating a mixture of the polycationic polymer and the zwitterionic compound on the outer surface of the blood-facing separating layer

Methodology Applied
Scientific EffectHydrophilic barrier formation: Hydrophile

Implementation Method 2

improved ability to immobilize anticoagulation agents like heparin

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 3

coating a mixture of the polycationic polymer and the zwitterionic compound on the outer surface of the blood-facing separating layer

Methodology Applied
Scientific EffectElectrostatic attraction: Electrostatic Induction

Implementation Method 4

enhanced convective properties for extended renal replacement therapy

Methodology Applied
Scientific EffectConvection: Convection

Data Source

PatentEP3296010B1Acrylonitrile-based membrane with low thrombogenicity
Publication Date: 2023.04.26 GAMBRO LUNDIA AB
  • EP3296010B1 patent drawingFigure 1A~1C
  • EP3296010B1 patent drawingFigure 2A~2B

AI summary

The present disclosure relates to improved semipermeable membranes based on acrylonitrile copolymers for use in dialyzers for the extracorporeal treatment of blood in conjunction with hemodialysis, hemofiltration or hemodiafiltration. The present disclosure further relates to methods of producing such membranes.