Nitric Oxide Delivery Device Using Copper Electrode

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Solution Overview

Problem

The delivery of nitric oxide (NO) to target sites is challenging due to its reactivity with hemoglobin and oxygen, and existing NO donors like diazeniumdiolates are unstable, making them unsuitable for commercialization, especially in biomedical applications where they can form toxic nitrosamines.

Innovation Solution

A nitric oxide delivery device comprising a housing with a copper-containing working electrode that generates Cu(I) ions to reduce nitrite ions and produce NO, using a two- or three-electrode configuration with controlled voltage pulses to manage NO release, ensuring stability and controlled delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If stable hydrophilic or hydrophobic NO donors are employed, then NO delivery stability is improved, but commercialization remains challenging due to instability of diazeniumdiolates and other NO donors

Engineering Contradiction:
ImproveNO donor stabilityVSAvoidcommercialization reliability
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent employs diazeniumdiolate salts as intermediary compounds that can be electrochemically converted to active NO donors. These salts are stable for storage and handling, but can be activated on-demand through electrochemical reduction at the cathode, providing both stability during storage and reliability during use. The intermediary salt form resolves the contradiction between stability and reliability.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical state of the NO donor from active diazeniumdiolate compounds to their stable salt forms for storage and transport. The active form is generated in-situ through electrochemical parameter changes (applied voltage/potential). This parameter change enables stable storage while maintaining the ability to generate active NO donors reliably when needed.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If MAHMA/NO is dispersed in silicone rubber matrix, then thrombus formation is prevented, but MAHMA/NO and diamine precursor leach from polymer matrix and form toxic nitrosamines

Engineering Contradiction:
Improvethrombus formationVSAvoidnitrosamine formation
Core Design Contradiction:
Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent uses stable diazeniumdiolate salts as intermediaries that are incorporated into the polymer matrix. These salt forms do not leach and form toxic nitrosamines like the active compounds do. The active NO donors are generated electrochemically from these stable intermediaries, preventing harmful leaching while maintaining anti-thrombotic efficacy.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the chemical storage and release mechanism (where MAHMA/NO is stored in the polymer and releases passively or through degradation) with an electrochemical generation mechanism. Voltages are applied to generate NO donors in-situ from stable salts, eliminating the need for chemical precursors that can leach and form toxic byproducts.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If diazeniumdiolates are used as NO donors, then NO release is achieved, but instability renders commercialization challenging

Engineering Contradiction:
ImproveNO releaseVSAvoiddiazeniumdiolate stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent performs preliminary action by converting unstable diazeniumdiolate compounds into their stable salt forms before device assembly and storage. These pre-prepared stable salts are then electrochemically converted to active NO donors during device operation. This preliminary stabilization action enables both NO release capability and long-term stability for commercialization.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces the chemical instability issue with an electrochemical solution. Instead of relying on the inherent (unstable) chemical properties of diazeniumdiolates for NO release, the system uses electrochemical reduction of stable diazeniumdiolate salts to generate active NO donors on-demand. This substitution of chemical storage for electrochemical generation resolves the stability-productivity contradiction.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

4Ease of operation

If electrochemical generation of NO is implemented, then controlled NO delivery is achieved, but device complexity increases with multiple electrodes and voltage control

Engineering Contradiction:
Improvecontrolled NO deliveryVSAvoidelectrode configuration complexity
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The patent integrates multiple functions into the device: the cathode generates NO donors electrochemically, the housing provides structural support and can be made permeable to NO, and the same device structure serves as both the electrochemical cell and the delivery system. This multi-functionality reduces overall device complexity despite the electrochemical generation requirement.

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

Solution Approach 2:

The device uses the applied voltage to drive both the electrochemical generation of NO donors and their subsequent release through the permeable housing. The system is self-regulating in that the rate of NO generation is directly controlled by the applied voltage, eliminating the need for separate control mechanisms. This self-service characteristic simplifies operation despite the electrochemical complexity.

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 device effectively generates and controls the release of nitric oxide, preventing biofilm formation and thrombosis, while minimizing toxicity, as demonstrated by reduced bacterial biofilm and thrombus formation in clinical settings.

Implementation Method 1

a working electrode, the working electrode being a copper-containing conductive material that produces a concentration of Cu(I) ions at a surface of the working electrode in response to an anodic voltage pulse applied thereto

Methodology Applied
Scientific EffectElectrochemical reduction: Electrolysis

Implementation Method 2

The reaction is a single electron transfer reaction that can be represented as: Cu(I) + NO2- → Cu(II) + NO + OH-

Methodology Applied
Scientific EffectSingle electron transfer reaction: Redox Reactions

Implementation Method 3

a housing that is permeable to nitric oxide; where nitrite in the source of nitrite ions is reduced by the Cu(I) ions to generate nitric oxide

Methodology Applied
Scientific EffectPermeation: Permeation

Data Source

PatentEP2830698B1Nitric oxide delivery devices
Publication Date: 2019.03.13 THE RGT UNIV OF MICHIGAN
  • EP2830698B1 patent drawingFigure 1A~1B
  • EP2830698B1 patent drawingFigure 2A~2C
  • EP2830698B1 patent drawingFigure 3A~4A

AI summary

A nitric oxide delivery device includes a housing that is permeable to nitric oxide. A working electrode (which is a copper-containing conductive material or a base material coated with a copper-containing conductive material) is positioned inside of the housing. A conductive lead is electrically connected to the working electrode and extends outside of the housing. A reference electrode and/or a counter electrode is electrically isolated from the working electrode. The reference electrode and/or the counter electrode has a first portion that is inside of the housing and a second conductive portion that is outside of the housing. A source of nitrite ions is to be contained within the housing such that it is in contact with the working electrode.