刘葭, 刘鑫, 赵颖, 王永洁, 刘欣妍, 孙铭忆, 吴清. 当归有效组分多元释药系统的构建与初步评价J. 药学学报, 2018,53(12): 1976-1985. doi: 10.16438/j.0513-4870.2018-0556
引用本文: 刘葭, 刘鑫, 赵颖, 王永洁, 刘欣妍, 孙铭忆, 吴清. 当归有效组分多元释药系统的构建与初步评价J. 药学学报, 2018,53(12): 1976-1985. doi: 10.16438/j.0513-4870.2018-0556
LIU Jia, LIU Xin, ZHAO Ying, WANG Yong-jie, LIU Xin-yan, SUN Ming-yi, WU Qing. Establishment and preliminary evaluation of multiple drug delivery system of effective components of Angelica sinensisJ. Acta Pharmaceutica Sinica, 2018,53(12): 1976-1985. doi: 10.16438/j.0513-4870.2018-0556
Citation: LIU Jia, LIU Xin, ZHAO Ying, WANG Yong-jie, LIU Xin-yan, SUN Ming-yi, WU Qing. Establishment and preliminary evaluation of multiple drug delivery system of effective components of Angelica sinensisJ. Acta Pharmaceutica Sinica, 2018,53(12): 1976-1985. doi: 10.16438/j.0513-4870.2018-0556

当归有效组分多元释药系统的构建与初步评价

Establishment and preliminary evaluation of multiple drug delivery system of effective components of Angelica sinensis

  • 摘要: 中药组分多元释药系统是由多组分、多单元构成的体系,根据各组分的性质特点,设计不同释药单元并进行组合,以达到提高生物利用度、增强药效的目的。本研究以当归中超临界提取物、酚酸类和多糖类有效组分为研究对象,以微丸为载体,构建适用于结肠炎及结直肠癌化学预防的多元释药系统。采用挤出-滚圆法制备当归多糖胃部释放微丸,以18~24目收率和平面临界角为指标,采用Box-Behnken试验设计和正交试验设计,分别优化微丸处方与工艺参数。参照课题组前期优化工艺制备超临界提取物与酚酸提取物结肠靶向微丸,并将其与多糖微丸组成当归有效组分多元释药系统,进行质量评价与体外释放研究,采用小动物活体成像法动态考察微丸在小鼠体内过程。确定的当归多糖胃部释放微丸的处方为:微晶纤维素6.5 g、多糖3.3 g、二氧化硅0.2 g和润湿剂(60%乙醇)7 mL;工艺参数为:挤出速率75 r·min-1、滚圆速率1 800 r·min-1和滚圆时间3 min。体内外研究表明,制备的当归有效组分多元释药系统具有良好的释放性能,多糖微丸在人工胃液及胃部快速释放;结肠靶向微丸的靶向性良好,在人工胃液中2 h内几乎不释放,在人工小肠液中4 h释放小于20%,在人工结肠液中6 h释放大于90%。

     

    Abstract: The multiple drug delivery system of components of traditional Chinese medicine is a system composed of multiple components and multiple units. According to the characteristics of each component, different drug delivery units are designed and combined to achieve the purpose of improving bioavailability and enhancing drug efficacy. In this study, supercritical extracts, phenolic acids, and polysaccharides derived from Angelica sinensis were examined as research objects, and a pellet-based vehicle was applied to construct a multiple drug delivery system for the treatment and chemoprevention of colitis and colorectal cancer. The extrusion-spheronization method was used to prepare pellets of Angelica polysaccharides which should be released in the stomach. The yield in 18-24 mesh and plane critical angle served as the index. The Box-Behnken design and the orthogonal design were used to optimize the formulation and parameters of pellets. According to a previous study, the colon specific pellets loading supercritical extracts and phenolic acid extracts were prepared by the optimized process. These two units of pellets were combined into the multiple drug delivery system of effective components of Angelica sinensis, and the quality evaluation and in vitro release study were conducted. The dynamic observation of pellets in mice was evaluated using small animal in vivo imaging system. The prescription of the Angelica polysaccharides gastric releasing pellets was:microcrystalline cellulose 6.5 g, polysaccharide 3.3 g, silica 0.2 g and 7 mL of 60% ethanol as wetting agent. The process parameters were as follows:extrusion rate at 75 r·min-1, rounding rate at 1 800 r·min-1, and rounding time for 3 min. Both in vivo and in vitro studies indicate that the prepared multiple drug delivery system of effective components of Angelica sinensis produced good release properties. The polysaccharide pellets could be rapidly released in the artificial gastric fluid and in the stomach. The colon specific pellets showed good targeting. They released little in the artificial gastric fluid within 2 hours, released less than 20% in the artificial intestinal fluid for 4 hours, and released more than 90% in artificial colon fluid for 6 hours.

     

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