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[1]赵文静,李亚男,王玉丽,等.药物与辅料相互作用差异与结构特征的相关性研究[J].天津医科大学学报,2021,27(03):279-284,290.
　ZHAO Wen-jing,LI Ya-nan,WANG Yu-li,et al.Study on the correlation between the difference of drugs and excipients interaction and their structural characteristics[J].Journal of Tianjin Medical University,2021,27(03):279-284,290.
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
27卷
期数:
2021年03期
页码:
279-284,290
栏目:
技术与方法
出版日期:
2021-05-30

文章信息/Info

Title:
Study on the correlation between the difference of drugs and excipients interaction and their structural characteristics
文章编号:
1006-8147(2021)03-0279-06
作者:
赵文静1; 李亚男1; 王玉丽2; 任晓文2; 汤立达3; 徐为人2
1.天津医科大学研究生院，天津300070；2.天津药物研究院释药技术与药动学国家重点实验室，天津 300193；3 .天津市新药设计与发现重点实验室，天津 300193
Author(s):
ZHAO Wen-jing1; LI Ya-nan1; WANG Yu-li2; REN Xiao-wen2; TANG Li-da3; XU Wei-ren2
1.Graduate School，Tianjin Medical University，Tianjin 300070，China; 2.State Key Laboratory of Drug Delivery Technology and Pharmacokinetics，Tianjin Institute of Pharmaceutical Research，Tianjin 300193，China；3.Tianjin Key Laboratory of Molecular Design And Drug Discovery，Tianjin 300193，China
关键词:
药物; 辅料; 相互作用; 阻滞率; 结构特征参数
Keywords:
drug; excipient; interaction; blocking rate; characteristic parameters of structure
分类号:
R94
DOI:
-
文献标志码:
A
摘要:
目的：探索药物的结构特征参数在预测药物与辅料相互作用中的规律。方法：采用两室渗透模型测定不同性质的21种药物的透膜速度，考察辅料对药物渗透的阻滞作用。通过计算药物的分子大小、电荷和形状相关的特征参数，考察药物特征参数与辅料相互作用的相关性。结果：根据12 h时9种辅料对21个药物渗透速度的影响，得到辅料对药物的阻滞率，将药物分为5类。第1类药物的阻滞率小于-25%，辅料表现出加速渗透作用；第2类药物对辅料不敏感，此类药物除非极性可及表面积（ASA_P）与偶极矩（dipole）参数外都与其他药物存在显著差异（Z=-0.704、-0.503，P=0.534、0.669）；第3类药物对表面活性剂敏感，此类药物的重原子数量（a_heavy）、分子范德华体积（vol）、正电荷可及表面积（ASA+）参数的差异显著（Z=-1.965、-2.211、 -2.111，P=0.047、0.024、0.035）；第4类对表面活性剂和崩解剂敏感，此类药物参数的差异不显著；第5类药物对多类辅料敏感，此类药物的负电荷可及表面积（ASA-）、ASA_P 、dipole 等参数的差异显著（Z=-2.836、-2.611、-2.462，P=0.003、0.007、0.012）。结论：分子大小、极性、形状指标能够较好预测药物与辅料相互作用关系。
Abstract:
Objective: To explore the regularity of the structural characteristic parameters of drugs in predicting the relationship between drugs and excipients. Methods：The two-compartment penetrating detection devices were used to determine the permeation rate of 21 drugs with different properties，and the blocking effect of excipients on drug permeation was investigated. By calculating the characteristic parameters related to the molecular size，charge and shape of drugs，the correlation between the characteristic parameters of the drug and the interaction of excipients was investigated. Results：According to the influence of 9 excipients on the penetration rate of 21 drugs at 12 h，the blocking rate of excipients on drugs was obtained，and the drugs were divided into five categories. The blocking rate of the first class of drugs was less than -25%，and the excipients showed accelerated permeation. The second class of drugs were not sensitive to excipients，and these drugs were significantly different from other drugs except ASA_P and dipole （Z=-0.704，-0.503；P=0.534，0.669）. The third class of drugs were sensitive to surfactants，and the parameters of a_heavy，vol and ASA+ of these drugs were significantly different（Z=-1.965，-2.211，-2.111；P=0.047，0.024，0.035）. The fourth class were sensitive to surfactants and disintegrants，and the parameters of these drugs were not significantly different. The fifth class of drugs were sensitive to many kinds of excipients，and the parameters of ASA-，ASA_P，dipole of drugs had significant differences（Z=-2.836，-2.611，-2.462；P=0.003，0.007，0.012）. Conclusion: The molecular size，polarity，and shape index can better predict the interaction with drugs and excipients.

参考文献/References:

[1] 何秉踊. 我国药用辅料行业期待更高质量发展[N].中国医药报，2019-05-27（4）
[2] 陈思雨，陈露露，王欣桐，等. 药用辅料对CYP3A活性的影响及其对仿制药质量和疗效一致性评价的指导作用[J]. 中国临床药理学与治疗学， 2020，25（4）: 460
[3] 杨锐，孙会敏，于丽娜，等. 药用辅料对药品安全性的影响[J]. 药物分析杂志，2012，32（7）: 1309
[4] 靳贵英. 药用辅料β-环糊精中7种重金属元素的分析[J]. 今日药学，2017，27（4）: 228
[5] Garcia-Arieta A. Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence[J]. Eur J Pharm Sci， 2014，65: 89
[6] 薛晶，许鸣镝，南楠，等. 原辅料及制剂处方工艺对口服固体制剂溶出行为的影响[J]. 中国新药杂志，2017，26（12）: 1370
[7] 李均艳，孟策，张卫敏，等. 羟丙基甲基纤维素对托拉塞米渗透的影响[J]. 现代药物与临床，2015，30（4）: 390
[8] 国家药典委员会. 中华人民共和国药典[M].二部. 北京：中国医药科技出版社，2015
[9] 黎少志，黄紫玉，任晓文，等. 基于药物与羟丙甲纤维素凝胶相互作用的缓释特征参数研究[J]. 中国新药杂志，2017，26（9）: 1059
[10] 王博，张来华，李苑新，等. 亲水凝胶骨架缓释片释药机制评价方法的研究进展[J]. 中国医药工业杂志，2009，40（10）: 782
[11] Shekhawat P B，Pokharkar V B. Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles[J]. Acta Pharm Sin B，2017，7（3）：260
[12] 陈娇婷，詹怡飞. 药用辅料的研发与应用[J]. 山东化工，2015， 44（18）：21

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备注/Memo

备注/Memo:
基金项目 国家重大新药创新专项（2017ZX09101001）；国家重点研究开发项目（2019YFAO9005600）
作者简介 赵文静（1994-），女，硕士在读，研究方向：药理学；
通信作者：徐为人，E-mail：xuwr@tjipr.com。
更新日期/Last Update: 2021-05-30