药学学报, 2020, 55(1): 45-53
引用本文:
黄浩洲, 冉飞, 林俊芝, 李梦琪, 邹文铨, 樊三虎, 杨明, 许润春, 韩丽, 张定堃. 多酚类液体制剂精细制造关键:多元沉淀形成原理与稳态重构[J]. 药学学报, 2020, 55(1): 45-53.
HUANG Hao-zhou, RAN Fei, LIN Jun-zhi, LI Meng-qi, ZOU Wen-quan, FAN San-hu, YANG Ming, XU Run-chun, HAN Li, ZHANG Ding-kun. The key to fine manufacturing of liquid polyphenol preparations: the principle of multi-precipitation with steady-state reconstruction[J]. Acta Pharmaceutica Sinica, 2020, 55(1): 45-53.

多酚类液体制剂精细制造关键:多元沉淀形成原理与稳态重构
黄浩洲1, 冉飞1, 林俊芝2, 李梦琪3, 邹文铨4, 樊三虎5, 杨明6, 许润春1, 韩丽1, 张定堃1
1. 成都中医药大学药学院, 西南特色中药资源国家重点实验室, 四川 成都 611137;
2. 成都中医药大学附属医院中心实验室, 四川 成都 610072;
3. 四川护理职业学院, 四川 成都 610100;
4. 四川大学化学学院, 四川 成都 610064;
5. 成都市三勒浆药业集团, 四川 成都 610000;
6. 江西中医药大学, 江西 南昌 330004
摘要:
植物多酚具有广泛的药理活性与应用前景,是天然产物研究热点之一。然而,多酚液体制剂具有特殊的物理相态与复杂的化学组成,在研制、生产及上市后均存在稳定性差、易产生沉淀的共性问题,是制约多酚液体制剂发展的瓶颈问题。本文以植物多酚液体制剂多元沉淀机制研究为例,探讨了多酚类液体制剂沉淀物是什么、沉淀如何形成、沉淀能否控制,以及三条沉淀途径的相互作用规律,并提出了鞣质酸水解与儿茶素类非酶氧化聚合反复诱导缔合胶体聚沉的不稳定机制模型。科学阐释了多酚溶液体系中的复杂理化变化过程及其诱导体系不稳定的微观机制,提出了多酚液体制剂稳态重构的工艺思路,有利于形成多酚液体制剂沉淀机制及控制方法的共性规律,这对于促进多酚类液体制剂的精细制造与高质量、高水平发展具有一定科学意义。
关键词:    多酚      液体制剂      胶体      精细制造      沉淀      自组装     
The key to fine manufacturing of liquid polyphenol preparations: the principle of multi-precipitation with steady-state reconstruction
HUANG Hao-zhou1, RAN Fei1, LIN Jun-zhi2, LI Meng-qi3, ZOU Wen-quan4, FAN San-hu5, YANG Ming6, XU Run-chun1, HAN Li1, ZHANG Ding-kun1
1. State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Pharmacy College, Chengdu University of TCM, Chengdu 611137, China;
2. Central Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China;
3. Sichuan Nursing Vocational College, Chengdu 610100, China;
4. College of Chemistry, Sichuan University, Chengdu 610064, China;
5. Sanajon Pharmaceutical Group, Chengdu 610000, China;
6. Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
Abstract:
Plant polyphenols have a wide range of pharmacological activities and application prospects. Liquid polyphenol preparations have special physical phases and complex chemical compositions, with problems such as poor stability and easy precipitation during production and marketing. Taking the multi-precipitation mechanism of plant polyphenol liquid preparations as an example,we discuss the chemistry and composition of the precipitation, how it forms, whether precipitationcan be controlled, and the interaction law of three precipitation approaches. An unstable mechanism model is proposed where hydrolyzed tannin hydrolysis and catechin non-enzymatic oxidative polymerization repeatedly induces associative colloid aggregation and precipitation. This study explains the complex physicochemical changes in polyphenol solutions and the microcosmic mechanism of instability in the induced system and proposes a steady state reconstruction of liquid polyphenol preparation consistent with the common law of precipitation and control. It has scientific significance for promoting the development and manufacture of high quality liquid polyphenol preparations.
Key words:    polyphenol    liquid preparation    colloid    fine manufacturing    precipitation    self-assembly   
收稿日期: 2019-07-16
DOI: 10.16438/j.0513-4870.2019-0567
基金项目: 国家自然科学基金面上项目(81973493);中国博士后基金面上项目(2017M623308XB);四川省杰出青年科技人才项目(19JCQN0009);成都中医药大学中药学学科特色创新科研团队(CXTD2018006).
通讯作者: 张定堃,Tel:13568982018,E-mail:465790643@qq.com;韩丽,E-mail:hanliyx@163.com
Email: 465790643@qq.com;hanliyx@163.com
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