A novel ion-exchange method,which involves ultrasonic salt hydrolysis,cation exchange,lithium resin treatment,chlorine dioxide oxidation,alcohol precipitation and drying,is employed to prepare low molecular weight heparin lithium from crude heparin sodium.The preparation conditions are optimized by means of Box-Behnken design experiments.The composition,structure,and properties of the products are characterized through using FT-IR,UV-Vis,1 H-NMR,XPS,and specific rotation.Additionally,the anticoagulant performance is evaluated through testing APTT,PT,and TT assays.Results indicate that three key process innovation links include ultrasonic salt hydrolysis,lithium resin exchange,and using ClO2 as the oxidation and decolorizing agent.Heparin lithium made under the optimized conditions has a potency of 173.3 IU·mg-1,a lithium content of 3.7%,and a specific rotation of+51.422°.Spectroscopic analysis verifies the high similarity between the structure of heparin lithium prepared and the standard heparin sodium,which retaining active groups such as—OSO-3,—COO-,and OH-.In vitro anticoagulation experiments demonstrate that the prepared heparin lithium displays strong anticoagulant activity,suggesting that the product affects the intrinsic and common coagulation pathways,making it suitable as a pre-coagulant for medical blood collection devices.
heparin lithiumnovel ion-exchange methodultrasonic salt hydrolysischlorine dioxide oxidationanticoagulant performance
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