發(fā)布時間：2018-01-07 22:28

  本文關(guān)鍵詞：姜黃素微丸及囊泡的制備工藝和生物利用度研究　出處：《青島科技大學》2017年碩士論文　論文類型：學位論文

  更多相關(guān)文章： 姜黃素 胃漂浮微丸 囊泡 熔融高速攪拌法 薄膜分散法 生物利用度

【摘要】：姜黃素有廣泛的藥理作用,對多種疾病的治療與預(yù)防有著很好的效果。但姜黃素在堿性條件下不穩(wěn)定、難溶于水,體內(nèi)生物利用度低,臨床應(yīng)用受限。本文將姜黃素制備成胃漂浮微丸和囊泡,胃漂浮微丸可延長姜黃素在胃內(nèi)的滯留時間,提高對胃部疾病(胃癌、胃炎)的治療效果,減少在腸道堿性部位的降解,改善姜黃素的生物利用度;囊泡可以提高水溶性,減慢姜黃素的釋放,延長血液循環(huán)的時間,靶向地作用于肝臟、脾臟,提高對肝癌、肝炎等疾病的療效。采用熔融高速攪拌法制備姜黃素胃漂浮微丸。以持續(xù)漂浮時間為指標,通過單因素考察和星點設(shè)計-效應(yīng)面法對胃漂浮微丸制備的處方和工藝進行了優(yōu)化。最佳處方和工藝為:制丸轉(zhuǎn)速為400r/min、投料量為80g、單硬脂酸甘油酯與硬脂酸質(zhì)量比為8:3、粘合劑的用量為60.35%、碳酸氫鈉的用量為6.875%、HPMC K100用量為13.83%。胃漂浮微丸形狀圓整規(guī)則,粒徑均一,持續(xù)漂浮時間大于8h,具有明顯的緩釋性能,體外釋放機制符合擴散/溶蝕模型。使用薄膜分散法制備姜黃素囊泡。以包封率為指標,通過單因素考察和星點設(shè)計-效應(yīng)面法對囊泡制備的處方和工藝進行了優(yōu)化。最佳處方和工藝為:司盤80和膽固醇質(zhì)量比為4.2:1、膽固醇和姜黃素質(zhì)量比為5:1、磷酸鹽緩沖液體積為20.9m L、水合轉(zhuǎn)速為381r/min、水合時間為1.5h、超聲時間為3min、水合溫度為50℃。所得囊泡包封率高達88.5%,平均粒徑為162nm,Zeta電位為(-28.9±2.7)mV,囊泡形狀圓整,具有明顯的緩釋性能,體外釋放機制符合Ritger-peppas平面擴散模型。對姜黃素胃漂浮微丸和姜黃素囊泡在家兔體內(nèi)的生物利用度進行研究。姜黃素胃漂浮微丸比姜黃素普通片的達峰時間顯著延長(分別為2.514±0.056h、1.378±0.023h),有一定的緩釋作用;平均滯留時間顯著增加(MRT(0-t)分別為6.120±0.266h、2.512±0.018h),體內(nèi)作用時間延長;藥時曲線下面積顯著增大(AUC(0-t)分別為1631.178±128.860ng·mL-1·h、601.409±3 3.036ng·mL-1·h),姜黃素吸收總量增加;姜黃素胃漂浮微丸的相對生物利用度為271.23%,生物利用度得到了顯著提高。姜黃素囊泡比姜黃素混懸液的達峰時間延長(分別為1.868±0.378h、1.226±0.012h),有一定的緩釋作用;平均滯留時間顯著延長(MRT(0-t)分別為6.604±0.209h、2.498±0.016h),體內(nèi)作用時間延長;藥時曲線下面積顯著增大(AUC(0-t)分別為2074.989±1 46.690ng·m L-1·h、803.475±23.335ng·m L-1·h),姜黃素吸收總量增加;姜黃素囊泡的相對生物利用度為258.25%,生物利用度得到了顯著提高。
[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，

本文編號：1394521