Depolymerized Sea Cucumber Glycosaminoglycan for Selective Anticoagulation
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Solution Overview
Problem
Natural fucosylated glycosaminoglycans from sea cucumbers exhibit both anticoagulant and platelet aggregation-inducing activities, making them difficult to use clinically for thrombotic disease prevention and treatment due to opposing effects and potential bleeding tendencies.
Innovation Solution
Depolymerization of fucosylated glycosaminoglycan from Thelenota ananas (THG) to produce depolymerized THG (dTHG) with a specific molecular weight range of 10000-16000 Da, which inhibits endogenous factor Xase and HC-II-dependent antithrombin without inducing platelet aggregation, thereby achieving selective anticoagulant potency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If natural fucosylated glycosaminoglycan is used for anticoagulant therapy, then anticoagulant potency is improved, but platelet aggregation-inducing activity increases causing harmful effects
Solution Approach 1:
The patent applies segmentation by depolymerizing the natural fucosylated glycosaminoglycan into smaller molecular weight fragments (10000-16000 Da). This fragmentation separates the anticoagulant function from the platelet aggregation-inducing function, retaining the former while eliminating the latter. The depolymerized product maintains anticoagulant potency through preserved active sequences while the reduced molecular size prevents platelet aggregation.
Solution Approach 2:
The patent changes the molecular weight parameter of the glycosaminoglycan from its natural high molecular weight state to a controlled range of 10000-16000 Da. This parameter change fundamentally alters the biological activity profile, maintaining anticoagulant effects while eliminating platelet aggregation effects. The specific molecular weight range is optimized to achieve selective anticoagulant potency.
2Object-affected harmful factors
If molecular weight is reduced to eliminate platelet aggregation activity, then safety is improved, but anticoagulant potency may be reduced
Solution Approach 1:
The patent optimizes the molecular weight parameter to a specific range (10000-16000 Da) that simultaneously achieves two goals: eliminating platelet aggregation activity while preserving anticoagulant potency. This precise parameter control ensures that the depolymerized product falls within a window where safety is improved without sacrificing therapeutic efficacy.
Solution Approach 2:
The patent replaces the mechanical/physical property of high molecular weight with a chemically modified structure that has optimized molecular weight and specific sequence characteristics. This substitution creates a new form of the glycosaminoglycan that achieves selective anticoagulant activity through controlled depolymerization and purification.
Data Source
AI summary
Disclosed is a depolymerized glycosaminoglycan from Thelenota ananas (dTHG), weight average molecular weight of which is about 8000˜20000 Da, and monosaccharide components of which are acetylgalactosamine (GalNAc), glucuronic acid (GlcUA), fucose (Fuc) or their sulfates (expressed as —OSO3−), in which molar ratio of GalNAc:GlcUA:Fuc:—OSO3− is about 1:(1±0.3):(1±0.3):(3.5±0.5). Said dTHG is a potent endogenous inhibitor of factor X, which has good anticoagulant and antithrombotic activity, and can be used for the prevention and/or treatment of thrombotic diseases. Also provided is a method for preparing said dTHG, which comprises steps of 1) extracting and obtaining fucosylated glycosaminoglycan (THG) from the body wall of Thelenota ananas; 2) depolymerizing THG to obtain dTHG by method of peroxide depolymerization or method of peroxide depolymerization catalyzed by catalyst of the fourth period transition metal ions; 3) removing impurities with lower and/or higher molecular weight in dTHG.