不同剂量合成冰片对复方中药湿疹乳膏体外透皮吸收影响及药效学研究

【目的】比较含有不同剂量合成冰片的复方中药湿疹乳膏体外透皮吸收效果及抗炎、抑制迟发型变态反应的药效学作用。【方法】以离体BALB/c裸小鼠皮肤为渗透屏障,采用改良Franz垂直扩散池,高效液相色谱法(HPLC)测定透皮接收液中苦参碱的含量,比较不同剂量的合成冰片对乳膏中苦参碱体外释放和透皮吸收行为的影响,同时观察其对二甲苯致小鼠耳肿胀,以及对2,4-二硝基氯苯(DNCB)诱导的小鼠迟发型超敏反应的影响。【结果】给药后2~48 h,含合成冰片的乳膏中苦参碱累积渗透量均高于无冰片乳膏,差异有统计学意义(P0.05);48 h后不同剂量冰片组累积渗透量比较,差异无统计学意义(P0.05)。各组给药后12 h体外经皮渗透基本达到稳态,且12 h后各组苦参碱累积渗透量均呈下降趋势。给药12 h内,渗透速率顺序为3%冰片1%冰片2%冰片0.5%冰片无冰片;12 h后冰片质量浓度越大,苦参碱含量降低越快。药效学结果:与空白对照组比较,含质量浓度1%、3%冰片的湿疹乳膏对二甲苯致小鼠耳廓肿胀急性炎症及DNCB诱发小鼠过敏性接触性皮炎有明显的抑制作用(P0.05);与曲咪新乳膏比较,质量浓度1%、3%冰片的湿疹乳膏均能降低血清中白细胞介素(IL)-4水平,差异无统计学意义(P0.05)。【结论】含质量浓度1%合成冰片的复方中药湿疹乳膏体外透皮吸收效果良好,可有效抗炎及抑制迟发型变态反应。

Research on In-vitro Percutaneous Absorption and Pharmacodynamics of Chinese Herbal Compound Cremor for Eczema with Different Mass Concentrations of Synthetic Borneol

Objective To compare in-vitro percutaneous absorption and pharmacodynamic actions of anti-inflammation and inhibiting delayed-type hypersensitivity of Chinese herbal compound cremor for eczema (CHCCE) with different mass concentrations of synthetic borneol. Methods By adopting modified Franz diffusion device add with isolated BALB/cnude mice skin as a barrier, in vitro percutaneous absorption effectiveness of CHCCE with different mass concentrations of borneol was compared by in vitro percutaneous test after the content of matrine was determined with high performance liquid chromatography(HPLC). Meanwhile, the effects of CHCCE with different mass concentrations of synthetic borneol on reducing dimethylbenzene-induced auricular edema and suppressing delayed-type hypersensitivity induced by 2,4-dinitrochlorobenzene(DNCB) in mice were compared. Results Cumulative permeation amount of matrine in CHCCE with synthetic borneol was higher than that in CHCCE without synthetic borneol 2～ 48 h after administration (P < 0.05). There was no significant difference of cumulative permeation amount (P>0.05) among CHCCE groups with different mass concentrations of synthetic borneol after 48 h. In vitro percutaneous absorption behavior of matrine arrived to the steady state and the cumulative permeation amount of matrine presented a decreasing trend in all medication groups 12 h after administration. Within 12 h of the medication, the permeation rate of CHCCE with different mass concentrations of borneol was in the sequence of 3％ borneol > 1％ borneol > 2％ borneol > 0.5％ borneol > no borneol. The content of matrine was decreased with the increase of mass concentration of synthetic borneol after 12 h. The results of pharmacodynamic actions of CHCCE showed that compared with the blank control group, CHCCE with 1％, 3％ synthetic borneol could significantly suppress the acute inflammation induced by dimethylbenzene and inhibit contact dermatitis induced by dinitrochlorobenzene (DNCB) in mice(P < 0.05). Compared with Triamcinolone Acetonide Acetate and Miconazole Nitrate and Neomycin Sulfate Cream, CHCCE with 1％, 3％synthetic borneol could decrease the serum level of IL-4, but the difference was insignificant(P>0.05). Conclusion CHCCE with 1％ synthetic borneol has good effects on in vitro transdermal absorption, and can suppress inflammation and delayed-type hypersensitivity effectively.