窄治疗指数药物多西他赛注射液无乙醇制剂的胶束性质对比研究

摘要/Abstract

摘要： 目的：研究比对不同配方的窄治疗指数药物多西他赛注射液配制的临床给药溶液胶束的性质。方法：选取不含乙醇的多西他赛注射液国产产品与含乙醇的原研参比制剂，对稀配后药液中所形成的胶束性质进行对比研究。结果：两种产品利用不同介质（0.9%NaCl注射液、5%葡萄糖注射液）稀配后得到的药液中，增溶剂的临界胶束浓度值无显著差异；胶束的平均粒径、分散系数基本一致；且2种产品稀配所形成胶束的稳定性均良好。结论：不同辅料的产品中增溶剂在稀配过程中均形成了稳定胶束，起到增加主药溶解度的作用。

关键词: font-size:medium, ">胶束；临界胶束浓度；稳定性

Abstract: Objective：To investigate the micelle properties of clinical administration solutions prepared by different formulations of narrow therapeutic index drug docetaxel injection.Methods：The properties of docetaxel-loadedmicelles formed in dilute solution without ethanol and the original product containing ethanol were compared and studied.Results： There was no significant difference in the critical micelles concentration(CMC) value of the solubilizer in the solution obtained by diluting the three products with different media(0.9% sodium chloride solution and 5% glucose injection). The average particle size and dispersion coefficient of micelles were almost the same. The micelles formed by dilute mixing of these two products had good stability.Conclusion： The solubilizers in the products with different excipients form stable micelles during the dilution process， which plays a role in increasing the solubility of the main drug.

Key words: font-size:medium, ">Micelles； Critical micelles concentration； Stability

中图分类号:

孙鹏, 曾佳, 吴正红. 窄治疗指数药物多西他赛注射液无乙醇制剂的胶束性质对比研究[J]. 中国药物评价, 2023, 40(1): 36-41.

SUN Peng, ZENG Jia, WU Zheng-hong. Comparative Study on Micellar Properties of Ethanol-Free Formulations of Docetaxel Injection with Narrow Therapeutic Index[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2023, 40(1): 36-41.

参考文献

[1]Ashrafizadeh M， Mirzaei S， Hashemi F， et al. New insight towards development of paclitaxel and docetaxel resistance in cancer cells： EMT as a novel molecular mechanism and therapeutic possibilities [J]. Biomedicine & Pharmacotherapy， 2021， 141.
     [2]Das T， Anand U， Pandey SK， et al. Therapeutic strategies to overcome taxane resistance in cancer [J].Drug Resistance Updates， 2021， 55.
     [3]陈敬华，申维玺，夏俊贤，等. 多西他赛联合奥沙利铂和替吉奥与DCF方案一线治疗晚期胃癌的对比研究[J].中华肿瘤防治杂志，2015，22(2)： 134-137.
     [4]Sweeney CJ， Chen YH， Carducci M， et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer [J].New England Journal of Medicine，2015，373(8)： 737-746.
     [5]程增江.窄治疗指数药物目录建立与特别监管探讨[J].中国食品药品监管，2020，(5)： 30-37.
     [6]Wang C， Yang Y， Cui X， et al. Three different types of solubilization of thymol in Tween 80： Micelles， solutions， and emulsions-a mechanism study of micellar solubilization[J].Journal of Molecular Liquids，2020， 306.
     [7]Tije AJ， Verweij J， Loos WJ， et al. Pharmacological effects of formulation vehicles-Implications for cancer chemotherapy [J]. Clinical Pharmacokinetics，2003， 42(7)： 665-685.
     [8]The U.S. Food and drug administration. FDA Drug Safety Communication： FDA warns that cancer drug docetaxel may cause symptoms of alcohol intoxication after treatment [EB/OL].(2016-1-15)[2022-11-01]. https：//www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-cancer-drug-docetaxel-may-cause-symptoms-alcohol.
     [9]The U.S. Food and drug administration. Drugs@FDA： FDA-Approved Drugs： Taxotere(Docetaxel)|Nda #020449 | Injectable；Injection | Prescription | Sanofi Aventis US [EB/OL].【2022-11-01】.https：//www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020449.
     [10]Sun B， Jing H， Mabrouk MT， et al. A surfactant-stripped cabazitaxel micelle formulation optimized with accelerated storage stability [J]. Pharmaceutical Development and Technology， 2020， 25(10)： 1281-1288.
     [11]Poirier E，Desbiens C， Poirier B，et al. Comparison of serious adverse events between the original and a generic docetaxel in breast cancer patients[J].Ann Pharmacother，2014，48(4)：447-455.
     [12] 黄仲义.原研药多西他赛特点及仿制药与其差距[J].上海医药，2019(15)：85-88.
     [13]杨锐，杨春花，王力峰，等. 不同方法测定两种表面活性剂的临界胶束浓度[J].广州化工， 2014， 42(12)： 116-118.
     [14]陈志东.窄治疗指数药物对新型抗肿瘤药物安全使用的提示[J].上海医药，2022，43(S2)：92-98.
     [15]Berezin DB， Kustov AV， Krest′yaninov MA，et al. The behavior of monocationic chlorin in water and aqueous solutions of non-ionic surfactant Tween 80 and potassium iodide [J]. Journal of Molecular Liquids， 2019， 283 532-536.
     [16]汪菊芬，吴旭日，陈依军.注射用难溶药物增溶技术的研究进展.药物生物技术[J].2014， 21(3)： 253-259.
     [17]邓玉晓，刘葵葵，赵思太，等.多西他赛注射液在不同pH溶媒中的稳定性研究[J].食品与药品，2018，20(5)：340-343.
     [18]于克炜.多西他赛聚合物胶束的研究[D].山东大学，2012.