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. doi: 10.16438/j.0513-4870.2019-0567
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. doi: 10.16438/j.0513-4870.2019-0567
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 reconstructionJ. Acta Pharmaceutica Sinica, 2020,55(1): 45-53. doi: 10.16438/j.0513-4870.2019-0567
Citation: 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 reconstructionJ. Acta Pharmaceutica Sinica, 2020,55(1): 45-53. doi: 10.16438/j.0513-4870.2019-0567

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

The key to fine manufacturing of liquid polyphenol preparations: the principle of multi-precipitation with steady-state reconstruction

  • 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。

     

    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.

     

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