目的采用多元定时释药技术制备复方丹参缓释胶囊。方法将处方药材精制后制备成复方丹参同步释放微丸,使用流化床包衣设备,先以3%低取代羟丙基纤维素、2%羟丙基甲基纤维素和1%十二烷基硫酸钠混合配成包衣液进行包衣作为溶胀层,包衣增重为12%;再将2%乙基纤维素溶于90%乙醇中,加入2%微粉化滑石粉和0.2%邻苯二甲酸二乙酯混合配成包衣液进行包衣作为控释层,制备包衣微丸。等量称取控释层包衣增重分别为0%、8%、16%、20%、24%、26%的包衣微丸,混合均匀,装入硬胶囊中,即得复方丹参缓释胶囊。结果当溶胀层处方及用量固定后,通过控制控释层的厚度,可使包衣微丸在预期的不同时间定时释药。将几种控释层增重不同的包衣微丸混合后制成复方丹参缓释胶囊,在溶出介质中,各种包衣微丸可以在不同时间依次释药。在模拟人体胃肠道pH变化条件下,丹酚酸B和三七总皂苷的f2值为66.9,丹酚酸B和冰片的f2值为69.0,三七总皂苷与冰片的f2值为58.0,三者能够同步释放且均呈现出明显的缓释特征。结论采用定时释药技术制备而成的复方丹参缓释胶囊中理化性质不同的各成分在缓释的同时可以达到同步释放,遵循了中药制剂复方配伍的整体观和用药思想。

Objective To prepare Compound Danshen Sustained-release Capsula by using multiparticulate time-controlled release technology.Methods Compound Danshen pellets were prepared with the refined medicinal materials.Then,compound Danshen coat-loaded pellets were prepared in a fluid-bed coater.The coating material of swelling layer was 3% low-substituted hydroxypropylcellulose,2% hydroxypropylmethylcellulose,and 1% sodium dodecyl sulphate.The coating load of swelling layer was 12%.The coating material of controlled layer was 2% ethylcellulose in 90% alcohol solution,mixture of 2% micronization talc and 0.2% diethyl phthalate.Finally,Compound Danshen Sustained-release Capsula was developed by encapsulating the six kinds of coated pellets whose coating load were 0%,8%,16%,20%,24%,and 26% at equivalent ratio in hard gelatin capsule.Results After formulation and coating load of swelling layer were fixed,the coated pellets would release active compositions in the different times expectably through regulating coating level of controlled layer.Several kinds of coated pellets whose controlled layer had different coating load were mixed and encapsulated into Compound Danshen Sustained-release Capsula.In the dissolution medium,the various kinds of coated pellets could release active compositions in accordance with time and show a characteristic of sustained-releasing as a whole.Under the simulated gastrointestinal pH conditions,the in vitro release tests of Compound Danshen Sustained-release Capsula was carried out.The value of similarity factor(f2) of salvianolic acid B and notoginseng saponin,salvianolic acid B and borneol,notoginseng saponin and borneol was 66.9,69.0,and 58.0,respectively.The release profiles of various compositions from Compound Danshen Sustained-release Capsula showed obvious sustained-release characteristic and no significant difference between them.Conclusion The results indicated that the multiparticulate time-controlled release technology made it possible that various components with extremely different physicochemical properties in sustained-release formulations of traditional Chinese medicinal compound recipe could get to release synchronously while sustained-releasing.That complies with the organic whole conception of compound compatibility of traditional Chinese medicinal compound recipe.

国家自然科学基金资助项目(30200363);福建省自然科学基金资助项目(2006J0116)