青藤碱原位液晶作为液体栓塞剂的流变特性研究

Rheological properties of sinomenine in situ liquid crystal as liquid embolic agent

制备3种不同处方的青藤碱原位液晶,并考察其原位前后的流变学性质,评价其用于栓塞的可行性。采用锥板夹具进行流变学实验,分别进行稳态流变学和非稳态流变学性质研究,并比较其原位前后的流变学性质差异。稳态流变学结果显示3种液体栓塞剂原位前后均为剪切变稀的非牛顿流体,原位前后黏度相差2-5个数量级;并具有一定的屈服值,原位前约10 Pa,原位后约4 500 Pa;各体系均有一定触变性,动力黏度基本不受剪切速率的影响,原位前均小于0.3 Pa·s,原位后大于1Pa·s,原位前后相差1个数量级;温度扫描结果显示在10-50℃各体系黏度均略有下降,但下降速率基本不变,原位前后黏度相差1-3个数量级。非稳态流变学结果显示原位前无明显线性黏弹区,表现为液体的性质;原位后线性黏弹区范围为应变γG＇,体系黏性占优势,在高频下G＇〉G″,体系弹性占优势,复合黏度的测试结果从侧面证实了该液体栓塞剂原位后可形成立方液晶（3号原位后在此条件下结构被破坏）。该实验采用DHR-2流变仪进行流变学性质研究,方法简单,结果可靠,可为产品的体外评价和实际应用提供更多理论参考。

Three different kinds of sinomenine in situ liquid crystal were prepared for different prescriptions,to investigate the rheological properties before and after in situ treatment and evaluate its feasibility for embolization. Rheological experiments were carried out with cone plate fixtures. Both the steady-state rheological and non-steady-state rheological properties of in-situ gels and the swelling gels were studied and compared. Steady-state rheological study results showed that all the three liquid embolic agents were non-newtonian fluid before and after in situ treatment,which would become less ropy when they were pressed with shear stress; their viscosities differed by 2-5 orders of magnitude. It had a yield value of about 10 Pa before in situ treatment and about 4 500 Pa after in situ treatment.All the six systems had thixotropy while their dynamic viscosities were not influenced by the shear rate,all less than 0. 3 Pa·s before in situ treatment more than 1 Pa·s after in situ treatment,differing by an order of magnitude. The results of temperature sweeping showed a slight decrease with a steady rate in viscosity within the range of 10-50 ℃,differing by 3-4 orders of magnitude. The results of unsteady rheology showed that there was no obvious linear viscoelastic region in the three kinds of agents,indicating the properties of liquid. After in situ treatment,their linear viscoelastic range γ 〈 1%（ No. 3 was 5%）,and their elastic modulus G＇ was larger than the viscous modulus G″,indicating the properties of solid. Frequency scanning results showed that for the systems at low frequencies,G″ 〉G＇,system viscosity in a dominant position; while at high frequencies,G＇ 〉 G″,system elasticity in a dominant position. The results of compound viscosity test also proved that the liquid embolic agent in situ can form a cubic liquid crystal（ the structure of No. 3 was destroyed after in situ treatment）. The DHR-2 rheometer was used to investigate the rheological properties of in situ gels with three different prescriptions. The method is simple and the result is reliable,which can provide more theoretical reference for the in vitro evaluation and practical application of the product.