共载细叶远志皂苷和β-细辛醚自微乳的制备及体外质量评价Preparation and in vitro quality evaluation of self-microemulsion co-loaded with tenuifolin and β-asarone
张婷;王镜;申宝德;朱君君;王立强;袁海龙;
ZHANG Ting;WANG Jing;SHEN Bao-de;ZHU Jun-jun;WANG Li-qiang;YUAN Hai-long;School of Medicine, Huaqiao University;Department of Pharmacy,Air Force Medical Center;Department of Pharmac,Air Force Medical Center;
摘要(Abstract):
制备并优化共载细叶远志皂苷和β-细辛醚自微乳(TF/ASA-SMEDDS),并进行质量评价。通过溶解度试验、单因素试验及伪三元相图的绘制,筛选TF/ASA-SMEDDS的处方组成;采用Box-Behnken效应面法,以载药量和粒径为考察指标筛选最优处方,并进行乳化外观、粒径、形态以及体外释放的考察。最终确定TF/ASA-SMEDDS的最优处方为辛酸癸酸三甘油酯-聚氧乙烯蓖麻油-丙三醇(10.8∶39.2∶50),其中细叶远志皂苷载药量为(5.563±0.065)mg·g(-1),β-细辛醚的载药量为(5.526±0.022)mg·g(-1),β-细辛醚的载药量为(5.526±0.022)mg·g(-1),乳化后可形成均一透明泛蓝光的纳米乳,粒径为(28.84±0.44)nm;TEM显示TF/ASA-SMEDDS乳化后可形成粒径均一的圆球状结构;体外溶出试验结果显示细叶远志皂苷和β-细辛醚溶出速率及释放度均显著提高。TF/ASA-SMEDDS制备工艺简单,可有效提高细叶远志皂苷和β-细辛醚的释放度。
To prepare and optimize the self-microemulsion co-loaded with tenuifolin and β-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g(-1),乳化后可形成均一透明泛蓝光的纳米乳,粒径为(28.84±0.44)nm;TEM显示TF/ASA-SMEDDS乳化后可形成粒径均一的圆球状结构;体外溶出试验结果显示细叶远志皂苷和β-细辛醚溶出速率及释放度均显著提高。TF/ASA-SMEDDS制备工艺简单,可有效提高细叶远志皂苷和β-细辛醚的释放度。
To prepare and optimize the self-microemulsion co-loaded with tenuifolin and β-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g(-1) for tenuifolin and(5.526±0.022) mg·g(-1) for tenuifolin and(5.526±0.022) mg·g(-1) for β-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and β-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and β-asarone.
关键词(KeyWords):
细叶远志皂苷;β-细辛醚;自微乳;伪三元相图;Box-Behnken效应面法;体外质量评价
tenuifolin;β-asarone;self-microemulsion;pseudo-ternary phase diagram;Box-Behnken response surface methodology;in vitro quality evaluation
基金项目(Foundation): 军队后勤科研重点项目(BKJ15J005,BKJ16J011);; 全军医学科技青年培育计划拔尖项目(17QNP028);; 福建省高校产学合作重大项目(2019Y4007);; 福建省泉州市2020年专项(2020SY001)
作者(Authors):
张婷;王镜;申宝德;朱君君;王立强;袁海龙;
ZHANG Ting;WANG Jing;SHEN Bao-de;ZHU Jun-jun;WANG Li-qiang;YUAN Hai-long;School of Medicine, Huaqiao University;Department of Pharmacy,Air Force Medical Center;Department of Pharmac,Air Force Medical Center;
DOI: 10.19540/j.cnki.cjcmm.20200922.301
参考文献(References):
- [1] 吕广云,王双双,杭太俊,等.远志-石菖蒲药对配伍前后远志化学成分定性定量分析[J].中国药科大学学报,2016,47(3):329.
- [2] 刘根,贺文彬,赵子强,等.基于中医传承辅助平台对老年性痴呆防治方剂核心药物组合的筛选研究[J].中国实验方剂学杂志,2016,22(7):223.
- [3] 李晓青,赵佳奇,田雅娟,等.远志、石菖蒲及其对药改善记忆的物质基础和作用机制研究进展[J].中国实验方剂学杂志,2019,25(3):190.
- [4] 王睿,费洪新,李晓明,等.石菖蒲的化学成分及药理作用研究进展[J].中华中医药学刊,2013,31(7):1606.
- [5] CHANG W,TENG J.β-Asarone prevents Aβ25-35-induced inflammatory responses and autophagy in SH-SY5Y cells:down expression Beclin-1,LC3B and up expression Bcl-2[J].Int J Clin Exp Med,2015,8(11):20658.
- [6] DONG H,GAO Z,RONG H,et al.β-Asarone reverses chronic unpredictable mild stress-induced depression-like behavior and promotes hippocampal neurogenesis in rats[J].Molecules,2014,19(5):5634.
- [7] 傅思莹,杨国柱,李翎,等.β-细辛醚对癫痫大鼠氨基酸递质受体表达的影响[J].中药材,2014,37(10):1837.
- [8] 孟雪,贾璞,张毅,等.P-gp调控的石菖蒲对远志成分肠吸收特性的影响[J].现代中药研究与实践,2019,33(5):19.
- [9] LV J,JIA H,JIANG Y,et al.Tenuifolin,an extract derived from tenuigenin,inhibits amyloid-β secretion in vitro[J].Acta Physiol (Oxf),2009,196(4):419.
- [10] 王君,刘新民,潘瑞乐.远志皂苷碱水解产物对乙酰胆碱酯酶抑制活性的研究[J].中南药学,2014,12(2):102.
- [11] 许亚萍,伍旭明.石菖蒲-远志药对配伍机制初步探讨[J].中华中医药杂志,2018,33(12):5629.
- [12] 王倩.远志皂苷水解物的药代动力学研究[D].北京:北京协和医学院,2012.
- [13] 李思远,杨志欣,张文君,等.基于UPLC-MS/MS的苦参总黄酮自微乳大鼠体内药动学研究[J].中草药,2019,50(20):5018.
- [14] PATEL M H,SAWANT K K.Self microemulsifying drug delivery system of lurasidone hydrochloride for enhanced oral bioavailability by lymphatic targeting:in vitro,Caco-2 cell line and in vivo evaluation[J].Eur J Pharm Sci,2019,138:105027.
- [15] 钟芮娜,汪小涵,王欣桐,等.石菖蒲挥发油自纳米乳的制备与质量评价[J].中国中药杂志,2018,43(20):4062.
- [16] EL-BADRY M,HAQ N,FETIH G,et al.Solubility and dissolution enhancement of tadalafil using self-nanoemulsifying drug delivery system[J].J Oleo Sci,2014,63(6):567.
- [17] GOO Y T,PARK S Y,CHAE B R,et al.Optimization of solid self-dispersing micelle for enhancing dissolution and oral bioavai-lability of valsartan using Box-Behnken design[J].Int J Pharm,2020,585:119483.
- [18] 颜洁,关志宇,朱卫丰,等.Box-Behnken效应面法优化自组装法制备葛根素壳聚糖/海藻酸钠口服纳米粒的处方与工艺研究[J].中草药,2019,50(23):5706.
- [19] 王建泽,颜仁梁,王兴荣,等.白藜芦醇纳米乳的制备及大鼠体内的药动学研究[J].中草药,2019,50(10):2319.
- [20] MORI D,JATIN D,RAMESH P,et al.Formulation and optimization of microemulsion based sparfloxacin in-situ gel for ocular delivery:in vitro and ex vivo characterization[J].J Drug Deliv Sci Tec,2020,55:101373
- [21] 岳正刚,谢培,刘红波,等.细叶远志皂苷碱水解制备工艺研究[J].临床医学研究与实践,2018(32):5.
- [22] 董玉,石任兵,刘斌.石菖蒲有效部位中α-细辛醚、β-细辛醚的含量测定[J].北京中医药大学学报,2007,30(5):340.
- 细叶远志皂苷
- β-细辛醚
- 自微乳
- 伪三元相图
- Box-Behnken效应面法
- 体外质量评价
tenuifolin - β-asarone
- self-microemulsion
- pseudo-ternary phase diagram
- Box-Behnken response surface methodology
- in vitro quality evaluation
- 张婷
- 王镜
- 申宝德
- 朱君君
- 王立强
- 袁海龙
ZHANG Ting- WANG Jing
- SHEN Bao-de
- ZHU Jun-jun
- WANG Li-qiang
- YUAN Hai-long
- School of Medicine
- Huaqiao University
- Department of Pharmacy
- Air Force Medical Center
- Department of Pharmac
- Air Force Medical Center
- 张婷
- 王镜
- 申宝德
- 朱君君
- 王立强
- 袁海龙
ZHANG Ting- WANG Jing
- SHEN Bao-de
- ZHU Jun-jun
- WANG Li-qiang
- YUAN Hai-long
- School of Medicine
- Huaqiao University
- Department of Pharmacy
- Air Force Medical Center
- Department of Pharmac
- Air Force Medical Center