目的 研究松果菊苷自微乳化给药系统（echinacoside self-microemulsion drug delivery system，Ech-SMEDDS），进行处方优化、质量表征及大鼠在体肠吸收特性考察。方法 以平衡溶解度、相容性和伪三元相图为评价指标对不同辅料（油相、乳化剂和助乳化剂）的种类进行筛选；采用中心复合设计-响应面法（central composite design-response surface methodology，CCD-RSM），以乳化时间和平均粒径为评价指标对辅料用量比例进行优化；对粒径、多分散指数（polydispersity index，PDI）和ζ电位进行检测；通过透射电子显微镜、HPLC法分别对其超微结构、载药量和包封率进行观察和分析；以粒径与PDI为评价指标对其稳定性进行评价；通过大鼠在体单向肠灌流实验考察不同肠段处Ech-SMEDDS中松果菊苷的吸收水平，计算速率常数（K_a）及表观吸收系数（P_app），评价其肠吸收特性。结果 确定Ech-SMEDDS的最优配方及其质量占比为甘油三月桂酸酯（glycerol trilaurate，GTL，15.47%）、聚山梨酯80（35.35%）、聚氧乙烯氢化蓖麻油40（23.57%）和聚乙二醇200（25.61%）。基于油相和乳化剂的相容性考察，以微乳等级和粒径为评判指标，确定质量比为2∶3的聚山梨酯80与聚氧乙烯氢化蓖麻油40作为复合乳化剂，进行Ech-SMEDDS制备。Ech-SMEDDS的外观为淡黄色，澄清透明，其分散液呈澄清透明溶液，经苏丹红-亚甲基蓝染料鉴定为O/W型乳液；平均粒径为（24.99±0.49）nm，PDI为0.19±0.01；ζ电位为（−5.36±0.08）mV；Ech-SMEDDS的超微结构呈现类球状结构，且形态均匀；载药量为（26.28±0.49）mg/g，包封率为（97.63±0.17）%，稳定性检测结果良好；在体单向肠灌流试验结果计算得到的K_a和P_app在各肠段均大于松果菊苷水溶液，即松果菊苷的肠吸收均有所提高，其中在回肠中的吸收最佳，在十二指肠、空肠、回肠、结肠的K_a分别为松果菊苷的1.48、2.24、2.16、1.86倍，P_app分别为松果菊苷的5.05、3.11、1.85、3.48倍。结论 制得Ech-SMEDDS具有载药量大、稳定性高和肠吸收良好的特性，为松果菊苷的药物开发及临床应用奠定理论基础，为新疆特色药用资源的产业化升级提供了创新思路。

Objective To study echinacoside self-microemulsion drug delivery system (Ech-SMEDDS) for prescription optimisation, quality characterisations and in vivo intestinal absorption in rats. Methods The different excipients (oil phase, emulsifier and co-emulsifier) were screened by equilibrium solubility, compatibility and pseudo-ternary phase diagram; the dosage ratio of excipients was optimised by central composite design-response surface methodology (CCD-RSM) using emulsification time and average particle size as the evaluating indexes; particle size, polydispersity index (PDI) and ζ potential were examined; The ultrastructure, drug loading and encapsulation rate were observed and analysed by transmission electron microscopy and HPLC, respectively; the stability of Ech-SMEDDS was evaluated by particle size and PDI; and the absorption level of echinacoside in Ech-SMEDDS at different intestinal segments was investigated by in vivo unidirectional intestinal perfusion in rats, and the intestinal absorption properties were evaluated by calculating the rate constants (K_a) and apparent absorption coefficients (P_app). Results The optimal formulation of Ech-SMEDDS and its mass ratio were determined to be glycerol trilaurate (GTL, 15.47%), Tween 80 (35.35%), polyoxyethylene hydrogenated castor oil 40 (23.57%) and polyethylene glycol 200 (25.61%). Based on the investigation of the compatibility of oil phase and emulsifier, the microemulsion grade and particle size were used as the judging indexes, and Tween 80 and polyoxyethylene hydrogenated castor oil 40 with the mass ratio of 2:3 were determined as the composite emulsifier for the preparation of Ech-SMEDDS. The appearance of the Ech-SMEDDS was light yellow, clarified and transparent, and its dispersion was in the form of clarified and transparent solution, which was identified by the Sudan red-methylene blue dye as the O/W. The average particle size was (24.99 ± 0.49) nm, the PDI was 0.19 ± 0.01; the ζ potential was (−5.36 ± 0.08) mV; the ultrastructure of Ech-SMEDDS showed a spherical structure with a homogeneous morphology; the loading capacity was (26.28 ± 0.49) mg/g, and the encapsulation rate was (97.63 ± 0.17)%. The results of stability test were good; K_a and P_app calculated from the results of in vivo unidirectional intestinal perfusion test were greater than echinacoside aqueous solution in all intestinal segments, i.e., the intestinal absorption of echinacoside was improved, among which the best absorption was found in the ileum, and the K_a in the duodenum, jejunum, ileum, and colon were 1.48, 2.24, 2.16, and 1.86 times of that in echinacoside, and P_app was 5.05, 3.11, 3.11, 3.11, and 1.86 times of that in echinacoside, respectively. Conclusion The Ech-SMEDDS produced in this study has the characteristics of high drug loading, high stability and good intestinal absorption, which lays a theoretical foundation for the drug development and clinical application of echinacoside, and provides an innovative idea for the industrial upgrading of Xinjiang’s characteristic medicinal resources.

R283.6

国家自然科学基金项目（81960772）；国家自然科学基金项目（82360795）；新疆维吾尔自治区自然科学基金重点项目（2022D01D14）；新疆维吾尔自治区2024年度“天山英才”医药卫生高层次人才培养计划（TSYC202401B014）；神经与肿瘤药物研发全国重点实验室开放研究课题（SKLSIM-F-2024175）