亚临界水耦合冷冻干燥法制备芹菜素纳米分散体

doi:10.11949/0438-1157.20200049

摘要/Abstract

摘要：

在溶剂(亚临界水)-反溶剂(去离子水)体系下，利用溶剂反溶剂沉淀耦合冷冻干燥法，对芹菜素原料药进行了纳米化及改性，制备出了超细芹菜素颗粒及其水相分散体。系统地探究了反溶剂温度、亚临界水温度、反应压力、表面活性剂种类与浓度对造粒过程产生的影响，并通过扫描电子显微镜(SEM)、红外吸收光谱(FTIR)、X射线衍射 (XRD)、质谱分析(MS)等手段对原料药和产物进行了对比分析。结果表明，当反溶剂温度为0℃，亚临界水温度为160℃、反应压力为5 MPa、表面活性剂γ-环糊精的质量分数为5%时，可得到粒径在20~30 nm范围内，分布均匀，稳定程度较高且具有较低结晶度的纳米颗粒。本文报道的芹菜素纳米颗粒制备方法，全程无有机溶剂参与，易于生物医用推广，为基于芹菜素的口服药物设计与开发提供了参考。

关键词: 芹菜素, 亚临界水, 反溶剂, 造粒, 绿色制备, 纳米颗粒

Abstract:

Under the system of solvent(subcritical water)-antisolvent(deionized water), based on the combination of subcritical water technology and freeze-drying processing, we prepared apigenin nanoparticles by nanocrystallization and modification. The study comprehensively explores the influencing factors, including the temperature of desolvation, the temperature of subcritical water, the pressure of reaction system, and surfactant concentration in the process of the granulation. The study compares raw materials and products through scanning electronic microscopy (SEM), Fourier transform infrared spectrophotometry (FTIR), X-ray diffraction (XRD) and mass spectrometry (MS). The results show that when the antisolvent temperature is 0℃, the subcritical water temperature is 160℃, the reaction pressure is 5 MPa, and the surfactant γ-cyclodextrin mass fraction is 5%, the particle size can be obtained at range 20—30 nm, the nanoparticles are evenly distributed, with high stability and low crystallinity. The preparation method of apigenin nanoparticles reported in this article, without the participation of organic solvents in the whole process, is easy for biomedical promotion, and provides a reference for the design and development of oral drugs based on apigenin.

Key words: apigenin, subcritical water, antisolvent, granulation, green synthesis, nanoparticles

中图分类号:

TQ 460.6⁺2

田济阳, 邹源佐, 蒲源, 王丹. 亚临界水耦合冷冻干燥法制备芹菜素纳米分散体[J]. 化工学报, 2020, 71(6): 2768-2779.

Jiyang TIAN, Yuanzuo ZOU, Yuan PU, Dan WANG. Preparation of apigenin nanoparticles by combining subcritical water technology with freeze-drying processing[J]. CIESC Journal, 2020, 71(6): 2768-2779.

图/表 15

图1 芹菜素化学结构式及原料药扫描电镜图

Fig.1 Chemical structure of apigenin and SEM image of the raw material

图2 亚临界水法制备芹菜素纳米颗粒实验装置1—加热套；2—高温高压反应釜；3—搅拌桨；4—过滤器；5—热电偶；6—样品收集装置；7—取样控制阀门；8—反应温度、搅拌转速、反应压力控制及检测系统；9—泄压阀门；10—压力表；11—搅拌电机；12—高精度高压泵出气控制阀门；13—高压高精度柱塞泵；14—高精度高压泵进气控制阀门；15—氮气气瓶

Fig.2 Schematic diagram of apigenin nanoparticles preparation by using SBCW method

图3 以亚临界水为溶剂，去离子水为反溶剂，芹菜素纳米颗粒的制备原理示意图

Fig.3 Schematic diagram of apigenin nanoparticles by using SBCW as solvent and deionized water as anti-solvent

图4 不同反溶剂温度下芹菜素扫描电镜图

Fig.4 SEM images of apigenin particles prepared at different anti-solvent temperature

图5 不同溶剂与反溶剂体积下芹菜素颗粒的SEM图

Fig.5 SEM images of apigenin particles obtained from different volume ratio of solvent/anti-solvent

图6 不同亚临界水温度下芹菜素颗粒的电镜图

Fig.6 SEM images of apigenin particles obtained from different temperatures of SBCW

图7 不同压力条件下芹菜素颗粒的电镜图

Fig.7 SEM images of apigenin particles obtained from different pressure

图8 使用不同表面活性剂制备的芹菜素颗粒扫描电镜图

Fig.8 SEM images of apigenin particles prepared by using different surfactant

图9 γ-环糊精化学结构式

Fig.9 Chemical structure of γ-cyclooctapentylose

图10 不同浓度γ-环糊精条件下制备的芹菜素颗粒扫描电镜图

Fig.10 SEM images of apigenin particles prepared at different concentrations of γ-cyclooctapentylose

图11 γ-环糊精对所制备纳米颗粒稳定性的影响

Fig.11 Effects of γ-cyclooctapentylose on stability of nanoparticles

图12 芹菜素原料药与制备的纳米颗粒红外分析对比图

Fig.12 FTIR spectra of the raw materials and apigenin nanoparticlesa—raw; b—apigenin nanoparticles; c—apigenin nanoparticles with γ-cyclooctapentylose

图13 芹菜素原料药与制备的纳米颗粒XRD谱图

Fig.13 XRD patterns of raw materials and apigenin nanoparticlesa—raw; b—apigenin nanoparticles; c—apigenin nanoparticles with γ-cyclooctapentylose

图14 芹菜素原料药与制备的纳米颗粒紫外可见吸收光谱对比图

Fig.14 UV-Vis spectra of raw materials and apigenin nanoparticlesa—raw; b—apigenin nanoparticles; c—apigenin nanoparticles with γ-cyclooctapentylose

图15 芹菜素原料药与制备的纳米颗粒质谱对比图

Fig.15 Mass spectra of raw and apigenin nanoparticlesa—raw; b—apigenin nanoparticles; c—apigenin nanoparticles with γ-cyclooctapentylose

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