姜黄素微丸及囊泡的制备工艺和生物利用度研究

发布时间：2018-01-07 22:28

  本文关键词：姜黄素微丸及囊泡的制备工艺和生物利用度研究　出处：《青岛科技大学》2017年硕士论文　论文类型：学位论文

  更多相关文章： 姜黄素 胃漂浮微丸 囊泡 熔融高速搅拌法 薄膜分散法 生物利用度

【摘要】：姜黄素有广泛的药理作用,对多种疾病的治疗与预防有着很好的效果。但姜黄素在碱性条件下不稳定、难溶于水,体内生物利用度低,临床应用受限。本文将姜黄素制备成胃漂浮微丸和囊泡,胃漂浮微丸可延长姜黄素在胃内的滞留时间,提高对胃部疾病(胃癌、胃炎)的治疗效果,减少在肠道碱性部位的降解,改善姜黄素的生物利用度;囊泡可以提高水溶性,减慢姜黄素的释放,延长血液循环的时间,靶向地作用于肝脏、脾脏,提高对肝癌、肝炎等疾病的疗效。采用熔融高速搅拌法制备姜黄素胃漂浮微丸。以持续漂浮时间为指标,通过单因素考察和星点设计-效应面法对胃漂浮微丸制备的处方和工艺进行了优化。最佳处方和工艺为:制丸转速为400r/min、投料量为80g、单硬脂酸甘油酯与硬脂酸质量比为8:3、粘合剂的用量为60.35%、碳酸氢钠的用量为6.875%、HPMC K100用量为13.83%。胃漂浮微丸形状圆整规则,粒径均一,持续漂浮时间大于8h,具有明显的缓释性能,体外释放机制符合扩散/溶蚀模型。使用薄膜分散法制备姜黄素囊泡。以包封率为指标,通过单因素考察和星点设计-效应面法对囊泡制备的处方和工艺进行了优化。最佳处方和工艺为:司盘80和胆固醇质量比为4.2:1、胆固醇和姜黄素质量比为5:1、磷酸盐缓冲液体积为20.9m L、水合转速为381r/min、水合时间为1.5h、超声时间为3min、水合温度为50℃。所得囊泡包封率高达88.5%,平均粒径为162nm,Zeta电位为(-28.9±2.7)mV,囊泡形状圆整,具有明显的缓释性能,体外释放机制符合Ritger-peppas平面扩散模型。对姜黄素胃漂浮微丸和姜黄素囊泡在家兔体内的生物利用度进行研究。姜黄素胃漂浮微丸比姜黄素普通片的达峰时间显著延长(分别为2.514±0.056h、1.378±0.023h),有一定的缓释作用;平均滞留时间显著增加(MRT(0-t)分别为6.120±0.266h、2.512±0.018h),体内作用时间延长;药时曲线下面积显著增大(AUC(0-t)分别为1631.178±128.860ng·mL-1·h、601.409±3 3.036ng·mL-1·h),姜黄素吸收总量增加;姜黄素胃漂浮微丸的相对生物利用度为271.23%,生物利用度得到了显著提高。姜黄素囊泡比姜黄素混悬液的达峰时间延长(分别为1.868±0.378h、1.226±0.012h),有一定的缓释作用;平均滞留时间显著延长(MRT(0-t)分别为6.604±0.209h、2.498±0.016h),体内作用时间延长;药时曲线下面积显著增大(AUC(0-t)分别为2074.989±1 46.690ng·m L-1·h、803.475±23.335ng·m L-1·h),姜黄素吸收总量增加;姜黄素囊泡的相对生物利用度为258.25%,生物利用度得到了显著提高。
[Abstract]:Curcumin has a wide range of pharmacological effects, and has a good effect on the treatment and prevention of many diseases. However, curcumin is unstable in alkaline conditions, insoluble in water, and low bioavailability in vivo. In this paper, curcumin was prepared into gastric floating pellets and vesicles. Gastric floating pellets could prolong the retention time of curcumin in the stomach and improve the therapeutic effect of curcumin on gastric diseases (gastric cancer, gastritis). The bioavailability of curcumin was improved by reducing the degradation in the basic part of intestinal tract and improving the bioavailability of curcumin. Vesicles can increase water solubility, slow curcumin release, prolong blood circulation time, target effect on liver and spleen, and increase liver cancer. The curative effect of hepatitis and other diseases. Curcumin gastric floating pellets were prepared by melting high speed agitation. The formulation and process of gastric floating pellets were optimized by single factor investigation and star design-effect surface method. The optimum formulation and process were as follows: the rotational speed of pellets was 400 r / min and the dosage was 80 g. The mass ratio of monostearate to stearic acid is 8: 3, the amount of binder is 60.35 and the amount of sodium bicarbonate is 6.875%. The dosage of HPMC K100 was 13.83. The shape of the pellets was regular, the particle size was uniform, and the floating time was more than 8 hours. The mechanism of in vitro release was consistent with the diffusion / dissolution model. Curcumin vesicles were prepared by thin-film dispersion method. The encapsulation efficiency was taken as the index. The formulation and process of vesicle preparation were optimized by single factor investigation and star design-effect surface method. The optimum formulation and process were as follows: Span 80 and cholesterol mass ratio 4.2: 1. The mass ratio of cholesterol to curcumin was 5: 1, the volume of phosphate buffer was 20.9 mL, the hydration speed was 381r / min, the hydration time was 1.5h and the ultrasonic time was 3min. When the hydration temperature was 50 鈩，

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