延胡索总碱理化性质及体外经皮渗透性的研究

Study on physicochemical properties and in vitro percutaneous permeability of total alkaloid of Corydalis Rhizoma

目的考察延胡索总碱的溶解度、油水分配系数等理化性质,研究促透剂及穴位、非穴位贴敷对其体外经皮渗透特性的影响,为指导其经皮给药剂型设计和制备提供参考。方法建立酸性染料比色法和高效液相色谱(high performance liquid chromatography,HPLC)法对延胡索总碱、延胡索甲素、延胡索乙素及延胡索丑素的含量进行测定,应用饱和溶液法和经典摇瓶法检测延胡索总碱的溶解性及油水分配情况;采用Franz扩散池法考察大鼠神阙穴与非穴位皮肤体外经皮渗透性能。结果结果显示,延胡索总碱纯度大于50%,其在10%乙醇的生理盐水中溶解性较好,可作为扩散池接收介质。当pH在5.5~7.2时,延胡索总碱的log P值控制在-1~0之间,说明延胡索总碱为强亲水性组分,延胡索甲素、延胡索乙素、延胡索丑素的log P值均在0~3之间,体外经皮渗透性良好,神阙穴用药组的24小时体外累积透过量和滞留量优于非穴位(P<0.05)。结论延胡索总碱具有适宜经皮渗透的理化性质及较好的经皮渗透性能,适宜制成经皮给药制剂,且经神阙穴用药具有一定优势,以上结果可为经皮给药剂型设计提供实验基础。

Objective To investigate the physicochemical properties such as the solubility and the oil-water partition coefficient of total alkaloid of Corydalis Rhizoma,and to study the effects of penetration enhancers and acupoint and non-acupoint application on its characteristics of percutaneous penetration in vitro,for providing references for the design and preparation of transdermal drug formulations.Methods The acid dye colorimetry method and HPLC method were used to determine the content of total alkaloids,Corydaline,Tetrahydropalmatine,and Tetrahydrocolumbamine.The solubility and oil-water distribution of total alkaloids of Corydalis Rhizoma were determined by saturated solution method and shaking flask method.Franz diffusion cell method was used to investigate the percutaneous permeability of Shenque acupoint and non-acupoint skin in rats.Results The results showed that the purity of total alkaloids of Corydalis Rhizoma was more than 50%,and its had well solubility in normal saline with 10%ethanol,so it could be used as a receiving medium for diffusion cells.When the pH value was between 5.5 and 7.2,the log P value of total alkaloids of Corydalis Rhizoma was between-1 and 0,indicating that the total alkaloids of Corydalis Rhizoma were strong hydrophilic components.The log P value of Corydaline,Tetrahydropalmatine,and Tetrahydrocolumbamine is between 0 and 3,the percutaneous permeability is feasible in vitro.In addition,the 24 hours cumulative permeation and retention in vitro of the Shenque acupoint group were better than that in the non-acupoints group(P<0.05).Conclusion The total alkaloids of Corydalis Rhizoma possesses appropriate physicochemical properties for percutaneous penetration and exhibits excellent percutaneous penetration,which are suitable for transdermal administration preparations.The Shenque acupoint medication has certain advantages.The above results can provide an experimental basis for the design of transdermal dosage forms.