Cao Jiao-Jiao, Huang Jie, Gui Shuang-Ying, Li Zheng-Guang, Li Qian, Zhang Yong, Wang Xing-Qi, Chu Xiao-Qin
Department of Pharmaceutics, Anhui University of Chinese Medicine, Hefei 230012, China.
Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei 230012, China.
Zhongguo Zhong Yao Za Zhi. 2018 Jun;43(12):2522-2530. doi: 10.19540/j.cnki.cjcmm.20180322.003.
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 °C, 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 evaluation and practical application of the product.
针对不同处方制备了三种不同的青藤碱原位液晶，以研究原位处理前后的流变学性质，并评估其栓塞可行性。采用锥板夹具进行流变学实验。研究并比较了原位凝胶和溶胀凝胶的稳态流变学和非稳态流变学性质。稳态流变学研究结果表明，三种液体栓塞剂在原位处理前后均为非牛顿流体，在剪切应力作用下会变得不那么黏稠；它们的黏度相差2 - 5个数量级。原位处理前其屈服值约为10 Pa，原位处理后约为4500 Pa。所有六个体系均具有触变性，其动态黏度不受剪切速率影响，原位处理前均小于0.3 Pa·s，原位处理后均大于1 Pa·s，相差一个数量级。温度扫描结果表明，在10 - 50℃范围内，黏度随温度缓慢下降，相差3 - 4个数量级。非稳态流变学结果表明，三种制剂均无明显的线性黏弹性区域，呈现液体性质。原位处理后，它们的线性黏弹性范围γ<1%（3号为5%），且弹性模量G'大于黏性模量G"，呈现固体性质。频率扫描结果表明，对于低频体系，G">G'，体系黏度占主导地位；而在高频时，G'>G"，体系弹性占主导地位。复合黏度测试结果也证明了原位液体栓塞剂可形成立方液晶（3号体系原位处理后结构被破坏）。使用DHR - 2流变仪研究了三种不同处方原位凝胶的流变学性质。该方法简单，结果可靠，可为该产品的评价和实际应用提供更多理论参考。
