Desulfated Polysaccharides for Reduced Bleeding Risk
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Solution Overview
Problem
Current anticoagulant therapies, particularly low molecular weight heparins, have significant anticoagulant activity that limits their use in treating non-coagulation mediated disorders due to bleeding risks, and there is a need for compounds with reduced anticoagulant activity while retaining anti-metastatic, anti-angiogenic, and anti-inflammatory effects.
Innovation Solution
Development of polysaccharide preparations with specific molecular weight ranges, reduced glycol split uronic acid residues, and controlled sulfation levels, which exhibit minimal anticoagulant activity but retain anti-Xa and anti-IIa activity, anti-metastatic, anti-angiogenic, and anti-inflammatory properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If low molecular weight heparins are used for anticoagulation therapy, then anticoagulant activity is improved, but bleeding risk increases
Solution Approach 1:
The patent extracts and removes the anticoagulant activity component from heparin by using desulfated derivatives and controlled depolymerization, isolating the anti-metastatic and anti-angiogenic properties while eliminating the harmful anticoagulant effect that causes bleeding
Solution Approach 2:
The patent changes the chemical parameters of heparin by controlling the degree of desulfation (removing sulfate groups) and molecular weight (depolymerization to 3,500-8,000 Da), which transforms the molecule from having strong anticoagulant activity to having minimal anticoagulant activity while retaining therapeutic benefits
2Object-affected harmful factors
If heparin derivatives with reduced anticoagulant activity are developed, then bleeding risk is reduced, but anti-metastatic and anti-angiogenic activity may be compromised
Solution Approach 1:
The patent applies local quality by making specific modifications to particular regions of the heparin molecule (N-desulfation and 6-O-desulfation at specific positions) while preserving the overall structure and other functional regions needed for anti-metastatic and anti-angiogenic activity
Solution Approach 2:
The patent optimizes specific parameters including molecular weight (3,500-8,000 Da), degree of desulfation (N-desulfation less than 40%, 6-O-desulfation less than 40%), and disaccharide composition (greater than 40% U2SHNS,6S residues) to simultaneously achieve reduced anticoagulant activity and maintained anti-metastatic/anti-angiogenic activity
3Object-affected harmful factors
If polysaccharide preparations with specific structural modifications are used, then anticoagulant activity is reduced, but manufacturing complexity increases
Solution Approach 1:
The patent segments the complex heparin molecule into smaller oligosaccharide units through controlled depolymerization, making the structure more manageable and easier to manufacture with defined properties while reducing anticoagulant activity
Solution Approach 2:
The patent establishes specific manufacturing parameters (molecular weight 3,500-8,000 Da, controlled desulfation levels, specific disaccharide composition) that provide clear targets for production and quality control, reducing manufacturing complexity despite the structural modifications required
Data Source
AI summary
Polysaccharide preparations lacking substantial anticoagulant activity are provided herein. Methods of making and using such preparations are provided.