黄连膏体外透皮吸收及抗炎活性研究

Transdermal absorption and anti-inflammatory activity of Huanglian ointment in vitro

目的:采用改良的Franz透皮扩散池考察黄连膏中主要活性成分的体外透皮吸收情况,同时对黄连膏的抗炎活性进行初步研究。方法:选用改良Franz透皮扩散池,接收液为30%乙醇生理盐水,以小鼠背部皮肤为透皮材料,采用紫外分光光度法及高效液相色谱法测定透皮接收液中盐酸小檗碱、芝麻酚、芝麻素及总生物碱的含量,计算透皮吸收动力学参数,考察黄连膏中抗炎活性成分的累计透过量及吸收规律;取30只SPF级小鼠,随机分为5组,即模型组、醋酸地塞米松乳膏组(100 mg·kg^(-1))、黄连膏高剂量组0.075 g·g^(-1)(生药/膏)、黄连膏中剂量组0.15 g·g^(-1)(生药/膏)、黄连膏低剂量组0.3g·g^(-1)(生药/膏),每组6只。阳性对照组为醋酸地塞米松乳膏组,进行2,4-二硝基氯苯(DNCB)致小鼠耳肿胀实验,观察黄连膏对炎症的抑制作用。结果:黄连膏中芝麻酚、盐酸小檗碱、芝麻素及总生物碱在24 h内的累积透过量分别为2.82,4.10,0.78,16.54μg·cm^(-2);稳态透皮速率(Js)分别为0.1252,0.1814,0.0342,0.7457μg·cm^(-2)·h^(-1);与阳性对照组比较,黄连膏高剂量组显著抑制DNCB所致小鼠耳肿胀。结论:黄连膏具有良好的体外透皮性能及抗炎活性,24 h内单位面积累积透过量随药物中主要有效成分含量升高而增加,经皮渗透行为符合零级动力学方程。

OBJECTIVE To employ improved Franz transdermal diffusion cell for examining the transdermal absorption of major active components in Huanglian ointment in vitro and exploring the anti-inflammatory activity of Huanglian ointment.METHODS A modified Franz transdermal diffusion cell was selected.The receiving solution was 30%ethanol saline and the transdermal material back murine skin.The contents of sesamol,berberine hydrochloride,sesamin and total alkaloid in transdermal receiving solution were determined by high performance liquid chromatography and ultraviolet spectrophotometry and the kinetic parameters of transdermal absorption calculated.The cumulative permeation quantity and absorption law of anti-inflammatory components in Huanglian ointment were examined.Thirty SPF mice were randomly divided into 5 groups of model,dexamethasone acetate cream(100 mg·kg^(-1)),high-dose Huanglian ointment 0.075 g·g^(-1)(crude medicine/ointment),middle-dose Huanglianointment 0.15 g·g^(-1)(crude medicine/ointment)and low-dose Huanglian ointment 0.3 g·g^(-1)(crude medicine/ointment)(n=6 each).Dexamethasone acetate cream group was selected as a positive control group.Ear swelling experiment induced by 2,4-dinitrochlorobenzene(DNCB)was carried out to observe the inhibitory effect of Huanglian ointment on inflammation.RESULTS The cumulative permeation rates of sesamol,berberine hydrochloride,sesamin and total alkaloids in Huanglian ointment within 24 h were 2.82,4.10,0.78 and 16.54μg cm^(-2) respectively.The steady-state penetration rates(Js)were 0.1252,0.1814,0.0342 and 0.7457μg cm^(-2)·h^(-1);As compared with positive control group,high-dose Huanglian ointment significantly suppressed ear swelling induced by DNCB in mice.CONCLUSION Huanglian ointment has excellent skin penetration and anti-inflammatory activity in vitro.Cumulative penetration per unit area within 24 h increases with higher content of major active components and transdermal penetration behavior accords with zero-order kinetic equation.