抗凝血硫酸化微晶纤维素钠构效关系的初步研究

Preliminary Study of Structure-Activity Relationship of Anticoagulant Sodium Microcrystalline Cellulose Sulfates

采用UV、IR、13CNMR和元素分析对3种由不同制备工艺参数所获得的硫酸化微晶纤维素钠(Na-MCS)进行结构分析,并研究其抗凝血活性。IR、UV揭示Na-MCS结构中含有硫酸酯基;13CNMR表明,3种Na-MCS的硫酸基取代模式相似,即C6取代占主导,C2位部分取代,C3位不发生取代;元素分析测得其硫酸取代度(DS)不同,即DSNa-MCS1=1 70、DSNa-MCS2=1 45、DSNa-MCS3=1 19;抗凝血研究表明,三者均可使血浆中活化部分凝血活酶时间(APTT)和凝血酶时间(TT)延长,但凝血酶原时间(PT)不延长,三者在抗凝血活性大小上存有差异,这与DS有关,在血浆中质量浓度为5μg/mL时,高DS的Na-MCS1使APTT达到155s、TT达34s,而低DS的Na-MCS3使APTT达到85s、TT达18s。构效关系分析表明,DS的差异不改变Na-MCS的抗凝血途径,但影响其抗凝血活性大小,DS越高,抗凝血活性越强。

Three sodium microcrystalline cellulose sulfates (i.e.Na-MCS1,Na-MCS2,Na-MCS3) prepared under different technological conditions were characterized by UV,IR and 13CNMR spectra and their anticoagulant activities were investigated.It was indicated that three Na-MCS exhibited essentially the same substitution pattern with the reactivity in the order of C6>C2>C3,among which,however,the degree of sulfation is different. Na-MCS1, which was highly sulfated with degree of sulfation 170,showed the best anticoagulant activity among three Na-MCS in prolonging activated partial thromboplastin time(APTT) and thrombin time(TT) of human plasma.