三七总皂苷传递体凝胶剂的制备及其离体皮肤渗透性研究

Study on preperation and transdermal permeation in vitro of Panax Notoginseng Saponins Transfersome Gel

目的制备三七总皂苷(PNS)传递体凝胶剂,并对其体外皮肤渗透性能和滞留特性进行考察。方法采用薄膜分散法制备PNS传递体,再以卡波姆-940为基质制备PNS传递体凝胶剂;对所制得的PNS传递体凝胶剂的稳定性与安全性进行初步评价;采用Franz扩散池法对PNS传递体凝胶剂进行体外透皮考察(以PNS脂质体凝胶剂为对照组),分别于上样后0.5、1、2、4、6、8、10、12、24、36 h取样,同时于36 h体外透皮试验完成后,取下离体皮肤用于PNS皮肤滞留量测定,以高效液相色谱法测定PNS的皮肤累积渗透量和皮肤滞留量。结果本研究制得的PNS传递体凝胶剂中各成分的含量分别为:人参皂苷Rg1(1.82±0.13)mg/g、人参皂苷Re(0.33±0.05)mg/g、三七皂苷R1(0.57±0.10)mg/g及人参皂苷Rb1(1.58±0.07)mg/g(n=3)。PNS传递体凝胶剂为细腻半透明浅白色胶体,皮肤刺激性小,在低温[(4±2)℃]和避光条件下稳定性良好。PNS传递体凝胶剂中各成分的36 h皮肤累积渗透量分别为:人参皂苷Rg1(601.70±42.26)μg/cm^2、人参皂苷Re(171.45±12.46)μg/cm^2、三七皂苷R1(327.23±16.41)μg/cm^2及人参皂苷Rb1(397.08±29.61)μg/cm^2(n=4),约为PNS脂质体凝胶剂的2.0~3.5倍。36 h后PNS脂质体凝胶剂中各成分的皮肤滞留量分别为:人参皂苷Rg1(8.16±1.60)μg/cm^2、人参皂苷Re(3.70±0.72)μg/cm^2、三七皂苷R1(5.34±0.95)μg/cm^2及人参皂苷Rb1(11.61±1.77)μg/cm^2(n=4),约为PNS传递体凝胶剂的2.0~7.0倍。结论 PNS传递体凝胶剂质量稳定,能促进药物的皮肤渗透。

Objective To prepare the Panax Notoginseng Saponins (PNS) Transfersome Gel and evaluate the transdermal permeation and skin deposition in vitro. Methods The PNS transfersomes were prepared by using the thin film dispersion method, and the Carbopol-940 was added as matrix for the preparation of the PNS Transfersome Gel. The stability and safety of the PNS Transfersome Gel was preliminary evaluated. In vitro transdermal experiments were done by Franz diffusion pool method and the PNS Liposome Gel was used as control group. Samples were taken in 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 36 hours after the preparation was loaded. And the in vitro skin was retained for the determination of the skin deposition quantity of the contents of PNS after the transdermal experiments. The skin cumulative permeated quantity and skin deposition quantity of the contents of PNS were determined by high performance liquid chromatography method. Results The contents of ginseng saponin Rg1, ginseng saponin Re, notoginsenoside R1 and ginseng saponin Rb1 of the PNS Transfersome Gel prepared in this study were (1.82±0.13),(0.33±0.05),(0.57±0.10) and (1.58±0.07) mg/g respectively (n=3). The PNS Transfersome Gel had a promising appearance with low skin irritation. It was stable when protected from light and kept at low temperature ([4±2]℃). The skin cumulative permeated quantity values of ginseng saponin Rg1, ginseng saponin Re, notoginsenoside R1 and ginseng saponin Rb1 of the PNS Transfersome Gel were (601.70±42.26),(171.45±12.46),(327.23±16.41) and (397.08±29.61)μg/cm^2 (n=4) respectively after 36 hours, the assayed components in PNS Transfersome Gel were about 2.0-3.5 times of those in the PNS Liposome Gel. While the skin deposition quantity values of ginseng saponin Rg1, ginseng saponin, Re notoginsenoside R1 and ginseng saponin Rb1 of the PNS Liposome Gel were (8.16±1.60),(3.70±0.72),(5.34±0.95) and (11.61±1.77)μg/cm^2 (n=4) respectively after 36 hours, the assayed components in PNS Liposome Gel were about 2.0-7.0 times of those in the PNS Transfersome Gel. Conclusion The PNS Transfersome Gel is stable and it can enhance the transdermal permeation efficiency of PNS.