Iron-Nitrosyl Hemoglobin Storage Stability and NO Delivery

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Solution Overview

Problem

Patients undergoing blood transfusions with blood substitutes or hemoglobins experience increased morbidity and mortality due to excess scavenging of nitric oxide leading to blood vessel constriction, as S-nitrosylated hemoglobin is unstable and not effectively used in transfusions.

Innovation Solution

Formation of stable iron-nitrosyl hemoglobin through reaction with inorganic nitrite at low concentrations, which upon oxygenation generates SNO-Hb with vasodilator and anti-platelet activity, reducing transfusion-related morbidity and mortality risks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If S-nitrosylated hemoglobin is used in blood substitutes, then vasodilator activity is achieved, but stability deteriorates causing deterioration during storage

Engineering Contradiction:

Improvevasodilator activityVSAvoidstorage stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by pre-forming iron-nitrosyl hemoglobin through incubation of nitrite with deoxygenated hemoglobin before transfusion. This stable precursor compound stores nitric oxide in a stable form that can be safely stored, and then converts to SNO-Hb in the patient's body to provide the needed vasodilator activity, thus achieving both stability during storage and therapeutic effect upon administration

Inventive Principle:

Principle #10Preliminary action

2Quantity of substance

If conventional blood substitutes are transfused, then oxygen transport is provided, but nitric oxide scavenging increases causing blood vessel constriction

Engineering Contradiction:

Improveoxygen transport capacityVSAvoidnitric oxide scavenging

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful nitric oxide scavenging effect into a beneficial therapy by engineering hemoglobin to carry and deliver nitric oxide rather than scavenge it. The iron-nitrosyl hemoglobin product donates nitric oxide to form SNO-Hb in the patient's circulation, transforming the original harmful scavenging behavior into a beneficial vasodilator and antiplatelet therapy that reduces transfusion-related morbidity and mortality

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

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 stable iron-nitrosyl hemoglobin product effectively mitigates transfusion risks by delivering nitric oxide and reducing blood vessel constriction, thereby decreasing mortality and morbidity associated with blood product transfusions.

Implementation Method 1

inorganic nitrite can mediate formation of iron-nitrosyl hemoglobin which is very stable and is oxygenated in the body to form SNO-Hb

Methodology Applied

Scientific EffectNitrosylation: Chemical Bonding

Implementation Method 2

upon oxygenation generates SNO-Hb

Methodology Applied

Scientific EffectOxygenation: Oxidation

Data Source

PatentUS8075922B2Method of co-infusing a deoxygenated hemoglobin containing blood substitute and inorganic nitrite

Publication Date: 2011.12.13 DUKE UNIV

AI summary

Contrary to current opinion that nitrite in general oxidizes hemoglobin with elimination of active nitric oxide, deoxygenated hemoglobin reacts with low concentration inorganic nitrite to produce very stable iron nitrosyl hemoglobin which on delivery into the body is converted to a hemoglobin capable of nitric oxide delivery and provides vasodilator and antiplatelet activity. This provides basis for ameliorated risk blood product transfusions.