论文部分内容阅读
制备了一种原位固化缓释注射剂,在牙周病变部位缓释药物达7 d,并对其体外性质及体内药动学进行考察。制备原位固化缓释注射剂,考察该注射剂的固化时间;利用扫描电镜对该注射剂固化后的表面形态进行了表征;测定0℃、25℃、37℃下凝胶剪切力随剪切率变化的曲线,绘制流变学曲线,并考察温度对黏度的影响;考察体外释放行为,并对其进行拟合;建立家兔牙周炎模型,考察其体内药动学。该注射剂稳定性良好,不易分层、分解,遇水后在6 s左右固化,可以黏附于牙周袋内,不易脱落;固化后,表面形成较多小孔,为药物扩散通道;在25℃、37℃下均为典型的牛顿流体,室温下通针性良好,使用方便;体外释放行为符合Korsmeyer-Peppas释放动力学方程,释放平缓,突释小,可持续7 d,能达到良好的缓释作用;药动学实验结果与各项参数的拟合结果表明了替硝唑原位固化缓释注射剂在体内缓释性能良好,制剂组可用一室模型进行很好的拟合,可维持牙龈沟液(GCF)内有效治疗浓度长达168 h,满足牙周炎临床治疗需要,该替硝唑原位注射缓释注射剂具有较好的应用前景。
A kind of in-situ cured sustained-release injection was prepared, and the drug was slowly released into the periodontal lesions for 7 days. The in vitro properties and in vivo pharmacokinetics were also investigated. The in-situ cured sustained-release injection was prepared and the curing time of the injection was investigated. The surface morphology of the injection after curing was characterized by scanning electron microscopy. The shear stress changes with shear rate at 0 ℃, 25 ℃, 37 ℃ The curve of rheology was drawn, and the influence of temperature on the viscosity was investigated. The in vitro release behavior was investigated and fitted. The model of rabbits periodontitis was established, and the pharmacokinetics of the model was examined. The injection has good stability and is difficult to delaminate and decompose, and can be cured after 6 seconds in water and can adhere to the periodontal pocket, so that the injection is difficult to fall off. After curing, many small holes are formed on the surface for drug diffusion channels; , 37 ℃ are typical Newtonian fluid, good through-needle properties at room temperature, easy to use; in vitro release behavior in line with Korsmeyer-Peppas release kinetics equation, release flat, small burst release, sustainable 7 d, can achieve good slow The result of pharmacokinetics and the fitting results of various parameters showed that the sustained-release in-situ formulation of tinidazole sustained-release injections was good in vivo and the formulation group could be well fit with one-compartment model to maintain the gingiva The effective therapeutic concentration in gully fluid (GCF) is as long as 168 h, which meets the clinical need of periodontitis. The in-situ injection of tinidazole injections has good application prospects.