Dextran Sulfate Parameter Control for IBMIR Reduction
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Solution Overview
Problem
Current dextran sulfate molecules have varying biological effects and toxicity levels due to differences in molecular weight and sulfation patterns, making it challenging to achieve improved biological effects without toxicity at pharmaceutically relevant dosages.
Innovation Solution
A dextran sulfate with a number average molecular weight between 1850 and 3500 Da, an average sulfate number per glucose unit between 2.5 and 3.0, and a sulfation of at least 90% at the C2 position, as measured by NMR spectroscopy, is developed to enhance biological effects while reducing toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dextran sulfate molecules have varying molecular weights and sulfation patterns to achieve different biological effects, then biological activity can be optimized, but toxicity increases at pharmaceutically relevant dosages
Solution Approach 1:
The patent applies parameter changes by precisely controlling the molecular weight (Mn 1850-3500 Da) and sulfation pattern (average sulfate number 2.5-3.0, with ≥90% sulfation at C2 position) of dextran sulfate to achieve improved biological effects while reducing toxicity. This systematic optimization of physical and chemical parameters resolves the contradiction between biological activity and toxicity.
2Reliability
If dextran sulfate is used as a potential substitute for heparin in anticoagulant therapy, then therapeutic efficacy can be achieved, but safety concerns arise due to toxicity
Solution Approach 1:
The patent optimizes the molecular weight and sulfation pattern parameters of dextran sulfate to achieve therapeutic efficacy as a heparin substitute while improving safety profile. The specific parameter ranges (Mn 1850-3500 Da, average sulfate number 2.5-3.0) are designed to balance anticoagulant activity with reduced toxicity.
3Reliability
If dextran sulfate molecules are synthesized with different sulfate contents and sulfation patterns, then biological activity can be enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent defines specific target ranges for sulfate content (average sulfate number 2.5-3.0) and sulfation pattern (≥90% at C2 position) that balance biological activity enhancement with manufacturing feasibility. These parameter specifications provide clear manufacturing guidelines while achieving superior biological effects.
Data Source
AI summary
Methods of treating, inhibiting and/or preventing instant blood-mediated inflammatory reaction (IBMIR) comprise administering, to a subject, a dextran sulfate characterized by a number average molecular weight (Mn) as measured by nuclear magnetic resonance (NMR) spectroscopy within an interval of 1850 and 3500 Da; an average sulfate number per glucose unit within an interval of 2.5 and 3.0; and an average sulfation of C2 position in the glucose units of said dextran sulfate of at least 90%, or a salt of such a dextran sulfate.