低分子质量肝素锂的制备及其体外抗凝血性能评价

Preparation of low molecular weight heparin lithium and evaluation of its in vitro anticoagulant performance

以肝素钠粗品为原料,采用超声盐解-阳离子交换转锂-二氧化氯氧化-醇沉-干燥的新型离子交换工艺制备低分子质量肝素锂。采用Box-Behnlen实验对制备工艺条件进行优化。通过FT-IR、UV-Vis、1HNMR、XPS、比旋光度等对产品进行组成、结构和性能表征,考察了其活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)体外抗凝3项指标。结果表明,盐解辅以超声、转锂时锂型树脂交换、ClO_(2)氧化脱色为该工艺改良的3个关键环节。最佳工艺条件下制得肝素锂效价为173.3 IU/mg,锂质量分数为3.6%,比旋光度为+51.422°。自制肝素锂与肝素钠标准品具有高度相似的结构特征,保留了肝素中—OSO_(3)^(-)、—COO^(-)、OH^(-)等活性基团。自制肝素锂展现出较强的体外抗凝血活性,主要通过内源凝性途径和共同途径作用于凝血过程,可作为医用采血器的预置抗凝剂。

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,~1H-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 ClO_(2)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.