Modified Bovine Heparin for Low-Bleeding VOC Therapy
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Solution Overview
Problem
Current treatments for sickle cell disease, particularly vaso-occlusive crisis, lack a specific acute therapy, and existing heparin compounds have high anticoagulant activity that increases bleeding risk.
Innovation Solution
A chemically modified bovine intestinal heparin with reduced anti-factor IIa activity and increased P-selectin inhibition, achieved by converting a portion of its free carboxylic acid moieties to 1-(3-dimethylaminopropyl)-3-ethylurea amide, allowing for therapeutic use with minimized bleeding risk.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional heparin is used to treat sickle cell disease, then anti-factor IIa activity is high providing strong anticoagulant effect, but bleeding risk increases
Solution Approach 1:
The patent applies chemical modification to change the molecular structure of heparin by converting carboxylic acid moieties to N-acylurea amide, which alters the pharmacological parameters to reduce anti-factor IIa activity while maintaining P-selectin inhibition, thus resolving the contradiction between anticoagulant effect and bleeding risk
Solution Approach 2:
The patent extracts and removes the harmful anticoagulant activity (anti-factor IIa) from the heparin molecule through selective chemical modification, while preserving the beneficial P-selectin inhibition property, thereby separating the useful effect from the harmful effect
2Object-affected harmful factors
If chemically modified heparin with reduced anti-factor IIa activity is used, then bleeding risk is minimized, but anticoagulant activity decreases
Solution Approach 1:
The patent converts the harmful high anticoagulant activity into a benefit by selectively reducing it through chemical modification, transforming the molecule into a variant that provides anti-inflammatory and anti-adhesive effects without excessive bleeding risk, effectively converting a harmful property into a beneficial therapeutic profile
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 heparin effectively treats or prevents vaso-occlusive crisis and other conditions by reducing inflammation and cellular adhesion, while minimizing anticoagulant side effects.
Implementation Method 1
The hallmark of SCD is vaso-occlusive crisis (VOC). VOCs are excruciatingly painful acute events and serve as an antecedent to severe complications such as acute chest syndrome (ACS), a type of acute lung injury and a major cause of death among SCD patients.
Data Source
AI summary
Provided is a chemically modified bovine intestinal heparin, as well as pharmaceutical compositions, compositions comprising chemically modified bovine intestinal heparin, and methods for making and using the same.