川芎提取物接枝型鼻用温敏凝胶制备及药效学研究

Preparation and pharmacodynamics of nasal thermosensitive gel containing Chuanxiong extract for grafting

目的以川芎提取物为模型药物,以阿魏酸为含量指标,采用高分子接枝工艺,将环糊精(CD)、壳聚糖(CS)制备成鼻用温敏凝胶,并对其进行体外释放考察和治疗偏头痛的药效学研究。方法将壳聚糖分子链与环糊精包合物以化学反应进行接枝,以其接枝产物溶解性为主要指标,考察反应时间、温度以及NaOH溶液浓度对其产物溶解性的影响。采用红外光谱法对环糊精是否成功接枝壳聚糖进行考察。以胶凝时间为指标,考察β-甘油磷酸二钠(β-GP)浓度、CS-CD配比、pH值对其影响。通过体外药物释放对药物释放性能进行评估。采用冰醋酸腹腔注射观察大鼠扭体反应。注射肾上腺素-冰水浴法制备急性血瘀模型,颈总动脉取血测血浆黏度以及内皮素(ET-1)含量。结果 NaOH浓度1 mol/L,20℃条件下搅拌共8 h。β-GP浓度56%、CS-CD配比0.8、pH值7。川芎提取物温敏凝胶可以延长大鼠扭体潜伏期,减少扭体次数,降低血浆黏度以及血浆中ET-1含量。结论环糊精接枝壳聚糖-温敏凝胶包合川芎提取物制备工艺简单,具有良好的缓释作用,且具有良好的治疗偏头痛的效果。

Objective Using Chuanxiong extract as a model drug and ferulic acid as a content indicator,cyclodextrin(CD)and chitosan(CS)were prepared into a nasal thermosensitive gel by using the polymer grafting process.Release of the drug was investigated in vitro,and pharmacodynamic investigation was performed on the treatment of migrane.Methods The chitosan molecular chain and the cyclodextrin inclusion complex were grafted by chemical reaction,and solubility of the grafted product served as the main indicator.The effects of reaction time,temperature and concentration of the NaOH solution on solubility of the product were investigated.Infrared spectroscopy was used to confirm whether cyclodextrin was successfully grafted with chitosan.Taking gelatin time as an indicator,the effects ofβ-glycerol phosphate disodium(β-GP)concentration,CS-CD ratio and pH value on it were investigated.Drug release performance was assessed based on drug release in vitro.The writhing response of rats was observed by intraperitoneal injection of glacial acetic acid.The acute blood stasis model was prepared by adrenaline injection-ice bath.Plasma viscosity and endothelin(ET-1)content were determined with blood collected from the common carotid artery.Results The NaOH concentration was 1 mol/L,and the mixture was stirred for 8 h at 20°C.Theβ-GP concentration was 56%,the CS-CD ratio was 0.8 and the pH value was 7.Chuanxiong extract thermosensitive gel could prolong the writhing latency of rats,reduce the number of writhing,lower plasma viscosity and plasma ET-1 content.Conclusion The cyclodextrin-grafted-with-chitosan thermosensitive gel incorporating Chuanxiong extract has simple preparation process,good sustained-release effect and excellent treatment effect on migraine.