川芎挥发油增加皮肤血流皮肤促透机制

 目的 阐明川芎挥发油的皮肤促透机制。方法 HPLC测定氟比洛芬含量,洗脱法、Franz扩散池、匀浆法分别考察给药2 h时的家兔体外和体内透皮特性,激光多普勒法测定皮肤血流。结果 给药2 h,川芎挥发油的离体皮肤促透作用未呈现浓度依赖性,3%浓度组进入皮肤总药量、接受液药量、皮肤累积药量分别较对照组增加2.38、2.30、2.44倍;而10%、15%浓度组却与对照组无显著性差异。川芎挥发油的在体皮肤促透作用具有浓度依赖性,15%浓度组较强,进入皮肤总药量、血药浓度分别较对照组增加1.98、2.21倍,而皮肤累积药量则为对照组的0.32。此外,川芎挥发油浓度依赖性增加皮肤血流灌注量,15%浓度组是对照组的4.81倍。缩血管物质去氧肾上腺素,显著降低了皮肤血流,离体皮肤无促透作用,但家兔体内抑制药物透皮,进入皮肤总量、血药浓度分别是对照组的0.71、0.60,而皮肤累积药量则为对照组的2.02倍。结论 川芎挥发油可能通过增加皮肤血流,促进药物从皮肤表皮和真皮层到毛细血管的消除,从而实现促透。

Mechanism of Enhancing Effect of Essential Oils from Ligusticum chuanxiong Hort. Through Rabbit Skin by Increased Skin Blood Flow

OBJECTIVE To evaluate the mechanism of skin enhancing effect of essential oils from Ligusticum chuanxiong Hort. METHODS The content of flurbiprofen was measured by HPLC method. The in vitro and in vivo transdermal characteristics at 2 h after topical application of gel to rabbit skin were investigated using the elution method, Franz diffusion cell, and the homogenization method, respectively. RESULTS The in vitro enhancement of chuanxiong oil did not show a concentration-dependent manner at 2 h after topical application. The group with 3% oil exhibited the highest values of drug absorbed from gel and drug permeation into receiver solution, and drug accumulated in skin, which were 2.38, 2.30, 2.44 times as the control. However, no difference was observed between the groups with 10% and 15% and the control. The in vivo enhancement of chuanxiong oil showed a concentration-dependent manner. The group with 15% oil exhibited the highest absorption capacity. The drug absorbed from gel and drug absorbed into plasma were increased by 1.98, 2.21 times compared with the control, respectively. While the value of drug accumulated in skin was only 0.32 times as the control. In addition, chuanxiong oil increased the skin blood flow concentration dependently. The group with 15% was increased by 4.81 times compared with the control. Phenylephrine was selected as a control for chuanxiong oil to reduce the local blood flow in skin because this agent causes the peripheral vasoconstriction, which did not show the skin enhancing effect through excised skin. However, phenylephrine significantly decreased absorption of flurbiprofen compared with the control in vivo. The drug absorbed from gel and drug absorbed into plasma were 0.71, 0.60 times as the control, respectively. While drug accumulated in skin was 2.02 times as the control. CONCULSION The increment of skin blood flow induced by chuanxiong oil resulted in enhancement of the clearance of the absorbed drug in epidermis and dermis into capillaries, which further enhanced rapid absorption of flurbiprofen from the stratum corneum into viable epidermis via the higher drug concentration gradient.