Objective: To investigate the characteristics of intestinal absorption kinetics of the anti-inflammatory extract (THAA) solid nanocrystals. Methods: Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) combining CORTECSTM UPLC-C18 column (100 mm×2.1 mm, 1.6 μm) and gradient elution of acetonitrile (A)-water (containing 0.1% formic acid, 5% methanol) (B) was used to establish quantitative analysis method to simultaneously determine the main effect components of THAA solid nanocrystals in vivo intestinal perfusion fluid of rats. Using in vivo unidirectional intestinal perfusion model of rats, the cumulative absorption, optimal absorption site and possible transport mechanism of THAA solid nanocrystals, raw materials, and common granular effect components in different intestinal segments of rats were investigated and compared. Results: The established quantitative analysis method for the simultaneous determination of 9 effective components of THAA solid nanocrystals in rat intestinal perfusion fluid was precise and accuratet, and could be used for intestinal absorption kinetics research. THAA solid nanocrystals retained the THAA effect intestinal absorption characteristics of the components with duodenum and ileum as the best absorption sites. And the intestinal absorption mechanism of neochlorogenic acid and chlorogenic acid might promote the diffusion process. Isoorientin-2’-O-rhamnoside, vitexin-2’-O-rhamnoside, isovitexin-2’-O-rhamnoside might be a passive absorption process. At high concentrations, orientin, isoorientin, vitexin, isovitexin might be saturation inhibition. Their absorption mechanism was not only a passive absorption process, but also active transport and facilitated diffusion. In addition, the apparent absorption coefficient(Papp), drug absorption constant (Ka), and umulative absorption percentage(P%) values of the effect component group of the THAA solid nanocrystal group in the duodenum, ileum, jejunum, and colon were significantly higher than those of the ordinary granule group and the raw material group (P all <0.05). And the intestinal absorption efficiency was in the following order: THAA solid nanocrystal, common granule, THAA raw material. Conclusion: The solid nanocrystalline drug delivery system can significantly improve the intestinal absorption efficiency of the THAA effect component group under different intestinal segments and different concentration levels by the nano-particles. It can be used for improving oral absorption of the insoluble effective part from the Chinese medicine.
[1] 吴淇浚·清. 植物名实图考[M]. 上海: 商务印书馆, 1957: 460
WU QJ·Qing Dynasty. Textual Research on Plant Names and Facts [M].Shanghai: The Commercial Press, 1957: 460
[2] 湖南省食品药品监督管理局. 湖南省中药饮片炮制规范[M]. 长沙: 湖南科学技术出版社, 2010: 358
Hunan Food and Drug Administration. Hunan Province Processing Specifications for Chinese Herbal Medicine Pieces [M]. Changsha: Hunan Science & Technology Publishing House, 2010: 358
[3] 浙江省食品药品监督管理局. 浙江省中药炮制规范 [M]. 北京: 中国医药科技出版社, 2016
Zhejiang Food and Drug Administration. Zhejiang Standard for Processing of Traditional Chinese Medicine [M]. Beijing: China Medical Science Press, 2016
[4] 福建省食品药品监督管理局. 福建省中药饮片炮制规范: 2012年版[M]. 福州: 福建科学技术出版社, 2013: 10
Fujian Food and Drug Administration. Processing Specifications of Fujian Traditional Chinese Medicine Pieces: 2012 Edition [M]. Fuzhou: Fujian Science & Technology Publishing House, 2013: 10
[5] 丁富娟, 李慧芬, 崔伟亮, 等. 三叶青名实考辨[J].中国实验方剂学杂志, 2018, 24(9): 208
DING FJ, LI HF, CUI WL, et al. Textual research on the name and facts of Trifolium repens [J].Chin J Exp Tradit Med Form, 2018, 24 (9): 208
[6] LI QL, XIN WX, ZHONG LK, et al. A study on the anti-tumor mechanism of total flavonoids from Radix Tetrastigmae against additional cell line based on COX-2-mediated Wnt/β-catenin signaling pathway[J].Oncotarget, 2017, 8(33): 54304
[7] 陈丹, 蔡韦炜, 范世明. 三叶青地上部分总黄酮的提纯方法:中国,CN104435401B[P]. 2018-06-08
CHEN D, CAI WW, FANG SM. Purification Method of Total Flavonoids from Aerial Parts of Trifolium repens: China,CN104435401B [P]. 2018-06-08
[8] 廖淑彬, 蔡韦炜, 陈丹, 等. 闽产三叶青地上部分提取物体内抗炎镇痛作用研究[J].中国现代应用药学, 2017, 34(3): 319
LIAO SB, CAI WW, CHEN D, et al. Study on the anti-inflammatory and analgesic effects of the extracts from the aerial parts of Fujian clover [J].Chin J Mod Appl Pharm, 2017, 34 (3): 319
[9] 廖淑彬, 陈丹, 刘秀棉, 等. 三叶青地上部分抗炎提取物质量控制研究[J].中国现代应用药学, 2020, 37(13): 1590
LIAO SB, CHEN D, LIU XM, et al. Study on quality control of anti-inflammatory extract from aerial parts of Trefoil trifolium [J].Chin J Mod Appl Pharm, 2020, 37 (13): 1590
[10] 廖淑彬, 陈丹, 余文静, 等. 三叶青地上部分抗炎提取物效应组分群不同生理状态体内组织分布规律及特性研究[J].中国中药杂志, 2021, 46(5): 1224
LIAO SB, CHEN D,YU WJ et al. Study on tissue distribution and characteristics of anti-inflammatory extract effect components of aerial part of Trefoil trifolium in different physiological states in vivo [J].Chin J Chin Mater Med, 2021, 46 (5): 1224
[11] 余文静, 陈丹, 熊朝栋, 等. 三叶青地上部分抗炎提取物固体纳米晶生物利用度及药动学研究[J].中国医院药学杂志, 2022, 42(4):385
YU WJ, CHEN D, XIONG CD, et al. Study on bioavailability and pharmacokinetics of solid nanocrystals of anti-inflammatory extracts from aerial parts of Trefoil trifolium [J].Chin J Hosp Pharm, 2022, 42 (4): 385
[12] 谢平,余文静,陈丹,等. 三叶青藤叶配方颗粒大鼠体内药代动力学生物等效性评价[J].药物分析杂志, 2020, 40(11):2017
XIE P, YU WJ, CHEN D, et al. Pharmacokinetic bioequivalence evaluation of Sanye Qingtengye formula granules in rats [J].Chin J Pharm Anal, 2020, 40 (11): 2017
[13] VELOSO SRS, ANDRADE RGD, CASTANHEIRA EMS. Magnetoliposomes: recent advances in the field of controlled drug delivery[J].Exp Opin Drug Del, 2021, 18(10): 1323
[14] ANUP N, CHAVAN T, CHAVAN S, et al. Reinforced electrospun nanofiber composites for drug delivery applications[J].J Biomed Mater Res A, 2021, 109(10): 2036
[15] BAGHERI F, DARAKHSHAN S, MAZLOOMI S, et al. Dual loading of Nigella sativa oil-atorvastatin in chitosan-carboxymethyl cellulose nanogel as a transdermal delivery system[J].Drug Dev Ind Pharm, 2021, 47(4): 569
[16] GOEL S, SACHDEVA M, AGARWAL V. Nanosuspension technology: recent patents on drug delivery and their characterizations[J].Rec Pat Drug Deliv Form, 2019, 13(2): 91
[17] 朱君君, 沈成英, 王镜,等. 甘草酸-F127/TPGS混合纳米胶束的制备及其大鼠在体肠吸收研究[J].中草药, 2020, 51(7):7
ZHU JJ, SHEN CY, WANG J, et al. Preparation of glycyrrhizine-F127/TPGS mixed nano micelles and its intestinal absorption in rats in vivo [J].Chin Tradit Herbal Drugs, 2020, 51 (7): 7
[18] 李玉玲, 冉鑫, 马桂芝. 去氢骆驼蓬碱衍生物DH-004大鼠在体肠吸收动力学研究[J].中国临床药理学杂志, 2021,37(7): 878
LI YL, RAN X, MA GZ. Study on absorption kinetics of harmine derivative DH-004 in rat intestine in vivo [J].Chin J Clin Pharmacol, 2021,37 (7): 878
[19] 高佳蕊, 牛立云, 朱晓霞,等. 基于UPLC-MS/MS技术和外翻肠囊模型探究M10-H和M10-Na在肠吸收的特征[J].药物分析杂志, 2021, 41(4):10
GAO JR, NIU LY, ZHU XX, et al. Based on UPLC-MS/MS technology and everted intestinal sac model, the intestinal absorption characteristics of M10-H and M10-Na were explored [J].Chin J Pharm Anal, 2021, 41 (4): 10
[20] 曾华平, 陈丹, 陈红, 等. 玳玳果黄酮降脂提取物在体肠吸收过程和转运机制研究 [J].中国现代应用药学,2021,38(3):286
ZENG HP, CHEN D, CHEN H, et al. Study on the absorption process and transport mechanism of flavonoid lipid reducing extract from hawkhawk fruit in vivo[J].Chin J Mod Appl Pharm, 2021, 38 (3): 286
[21] 廖淑彬, 陈丹, 陈红, 等. 三叶青地上部分抗炎提取物效应组分群不同生理状态在体肠吸收动力学及转运机制研究[J].中国医院药学杂志,2021,41(6):567
LIAO SB, CHEN D, CHEN H, et al. Study on absorption kinetics and transport mechanism of anti-inflammatory extracts from aerial parts of Trifolium repens under different physiological conditions in vivo [J].Chin J Hosp Pharm, 2021, 41 (6): 567
