Sulfated Cellobioside Compounds for NET Neutralization
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Solution Overview
Problem
Current treatments are inadequate for managing NET-mediated ailments such as sepsis, SIRS, and ischemia reperfusion injury, as they fail to effectively neutralize the cytotoxic effects of NETs without impairing the beneficial immune functions of neutrophils.
Innovation Solution
The use of polyanionic sulfated cellobiosides, specifically modified with a small uncharged glycosidically linked substituent at the reducing terminus, which interact electrostatically with NETs to neutralize their cytotoxic properties while maintaining chemical stability and immune function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If polyanionic sulfated cellobiosides are used to neutralize NETs, then cytotoxic activity of NETs is reduced, but chemical stability of the compound deteriorates
Solution Approach 1:
The patent applies composite material principles by combining sulfated cellobioside moieties with additional functional groups (such as amino sugars or other stabilizing moieties) to create a composite molecular structure. This composite structure maintains the polyanionic charge necessary for NET neutralization while incorporating stabilizing components that prevent degradation, thereby simultaneously achieving cytotoxicity reduction and chemical stability enhancement.
Solution Approach 2:
The patent employs parameter changes by modifying the molecular structure of sulfated cellobiosides through controlled sulfation degrees, molecular weight adjustments, and incorporation of stabilizing functional groups. These parameter modifications allow the compound to maintain sufficient negative charge for NET interaction while improving chemical stability through optimized structural parameters that resist degradation.
2Object-affected harmful factors
If polyanionic sulfated cellobiosides are used to neutralize NETs, then tissue damage is reduced, but beneficial immune functions of neutrophils are impaired
Solution Approach 1:
The patent applies local quality principles by designing compounds with specific structural characteristics that enable selective interaction with pathological NETs while sparing normal neutrophil functions. The modified sulfated cellobiosides possess localized functional groups that target specific components of dysfunctional NETs, allowing neutralization of harmful NETs while preserving the ability of intact neutrophils to perform beneficial immune functions such as phagocytosis and pathogen clearance.
Solution Approach 2:
The patent employs intermediary principles by using modified sulfated cellobiosides as mediator molecules that selectively bind to and neutralize pathological NETs without directly interfering with normal neutrophil function. These intermediary compounds act as bridges that specifically target dysregulated NET components, allowing the immune system to maintain its beneficial functions while the mediator compounds handle the neutralization of harmful NETs.
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
These compounds effectively ameliorate or inhibit NET-associated complications by neutralizing the cytotoxic activity of NETs, thereby reducing tissue damage and improving patient outcomes in conditions like sepsis, SIRS, and ischemia reperfusion injury.
Implementation Method 1
which interact electrostatically with NETs to neutralize their cytotoxic properties
Data Source
AI summary
The present invention relates to compounds with high chemical stability and methods for inhibiting the pathological activity of NETs in a subject. In particular, the invention relates to compounds with high chemical stability, uses thereof and methods for inhibiting or ameliorating NET mediated ailments (such as, for example, sepsis, systemic immune response syndrome (SIRS) and ischemia reperfusion injury (IRI)). More particularly, the invention relates to methods and uses of a polyanionic sulfated cellobioside modified with a small uncharged glycosidically linked substituent at its reducing terminus, wherein the presence of the substituent results in a molecule with high chemical stability without affecting the ability of the molecule to be effective in the therapy of NET mediated ailments. For example, the present invention relates to methods and uses of β-O-methyl cellobioside sulfate (mCBS) or a pharmaceutically acceptable salt thereof (e.g., mCBS.Na), in the therapy of a range of NET mediated ailments in subjects.