目的 优化三七总皂苷(PNS)传递体的处方,验证其治疗大鼠急性软组织损伤的作用。方法 采用薄膜分散法制备PNS传递体,以传递体弹性为指标,通过均匀设计法优化其处方工艺;分别以挤出法、离心超滤法测定传递体的弹性与包封率;通过对实验动物的损伤症候指数、血液流变学及组织形态学的观测评价传递体对大鼠急性软组织损伤的治疗作用,并与阳性对照药青鹏软膏进行比较。结果 PNS传递体最佳处方为PNS 100 mg、胆固醇15 mg、大豆磷脂120 mg、维生素E 2 mg、中药挥发油(柠檬烯-柠檬醛4:1)80 mg、水化液[磷酸盐缓冲液(PBS),pH 5.0]10 mL;以最佳处方制得的成品弹性为(2.74±0.32)min、粒径为(123.60±0.36)nm、Zeta电位为(-36.67±2.29)mV,人参皂苷Rg₁与人参皂苷Rb₁的包封率分别为(82.42±0.69)%、(94.40±0.74)%;药效学实验结果显示,与模型组相比PNS传递体可显著降低实验动物的损伤证候指数(P < 0.01)、全血黏度及血浆黏度(P < 0.05),有效改善病灶部位组织形态。结论 所得PNS传递体粒径适宜,弹性与药物包封率良好,疗效确切。

Objective To optimize the formulation of Panax notoginseng saponins (PNS) transfersomes and to verify their effects on acute soft tissue injury in rats. Methods Thin film dispersion method was employed to prepare PNS transfersomes. Based on the elasticity of transfersomes, PNS transfersomal formulation was optimized by a uniform experimental design. Extrusion method and centrifugation-ultrafiltration method were respectively adopted to determine the elasticity and the entrapment efficiency (EE) of PNS transfersomes. The therapeutic effects of PNS transfersomes on acute soft tissue injury in rats were evaluated by observing the indexes of injury symptom, the hemorheology and the histomorphology with Qingpeng Ointment being used as positive control. Results The optimum formulation was as follows: PNS 100 mg, cholesterol 15 mg, soybean phospholipid 120 mg, vitamin E 2 mg, volatile oils (limonene-citral = 4:1) 80 mg, and hydration liquid (phosphate buffered saline, pH 5.0) 10 mL. The optimized PNS transfersomes had elasticity of (2.74 ± 0.32) min, average size of (123.6 ± 0.36) nm, Zeta potential of (-36.67 ± 2.29) mV, and EE of (82.42 ± 0.69)% and (94.40 ± 0.74)% for ginsenoside Rg₁ and ginsenoside Rb₁, respectively. The results of pharmacodynamical tests showed that the PNS transfersomes could significantly improve the injury symptom indexes (P < 0.01) and hemorheology (P < 0.05) of the rats compared with model control, and it could also improve their histomorphology. Conclusion The optimized PNS transfersomes with an appropriate size, desired elasticity, and drug EE are effective for the acute soft tissue injury in rats.

高等学校博士学科点专项科研基金(20123322120002);浙江中医药大学校级科研基金人才专项项目(2012ZR06)