【摘要】：本研究以提高高烏甲素(LA)水溶性并使其具有緩釋效果,利用現(xiàn)代新藥制劑技術(shù)中的藥物包合技術(shù)和微球的載藥技術(shù)來制備高烏甲素-p-環(huán)糊精聚合物(β-CDPH)包合物和高烏甲素-β-環(huán)糊精載藥微球。同時(shí)分別對(duì)已經(jīng)制備出的包合物和空白微球進(jìn)行表征及性能的研究。并對(duì)制備出的聚合物包合物和載藥微球分別進(jìn)行載藥量和包封率測(cè)定,對(duì)載藥微球的制備工藝進(jìn)行進(jìn)一步的正交試驗(yàn)優(yōu)化分析。最后模擬人體胃、腸及血液pH值環(huán)境對(duì)包合物和載藥微球進(jìn)行體外釋放實(shí)驗(yàn)并為了了解制劑藥物釋放機(jī)理而進(jìn)行了動(dòng)力學(xué)方程擬合。實(shí)驗(yàn)結(jié)果為β-CDPH與LA能形成1：1摩爾比包合物,包合物中LA平均含量可達(dá)(27±1.1)%,且對(duì)LA增溶量可達(dá)11978mg/L,分別是LA-β-CD包合物增溶量的3.9倍、LA-β-CDPL包合物增溶量的1.5倍,高聚物包合物體外釋放結(jié)果表明,在模擬血液的pH值環(huán)境中藥物釋放能夠達(dá)到8小時(shí)。浸泡載藥法制備載藥微球的最佳工藝為反應(yīng)中溶劑乙醇的濃度為70%,反應(yīng)載藥微球浸泡溫度為45℃,微球與藥物質(zhì)量比為1：1,載藥微球浸泡時(shí)間72h由此可得到載藥率為(16.5±1.1)%的載藥微球。載藥微球體外釋放實(shí)驗(yàn)表明,在模擬腸液pH值環(huán)境下藥物的釋放時(shí)間可長(zhǎng)達(dá)20小時(shí),并且其符合零級(jí)釋放動(dòng)力學(xué)曲線擬合方程和Ritger-Peppas方程。 本試驗(yàn)制備的新藥制劑技術(shù)簡(jiǎn)單、易行,高聚物包合物能大大提高高烏甲素的水溶性,而且使高烏甲素包合物在模擬人體血液pH值環(huán)境下具有了一定的緩釋效用。載藥微球在模擬人體腸液pH值環(huán)境下能夠使高烏甲素達(dá)到長(zhǎng)效緩釋的效果,從而能夠方便患者的需要,顯著減少給藥次數(shù)。
[Abstract]:The aim of this study was to improve the water solubility of (LA) and to make it have slow release effect. In this paper, the new drug inclusion technology and the drug loading technique of microspheres were used to prepare the inclusion complexes of rapeconitin-p-cyclodextrin polymer (尾 -CDPH) and the drug loaded microspheres of aconitin-尾 -cyclodextrin. At the same time, the characterization and properties of the inclusion complexes and blank microspheres were studied. The drug loading and encapsulation efficiency of the polymer inclusion compound and the drug loaded microspheres were determined, and the preparation process of the drug loaded microspheres was optimized by orthogonal test. Finally, in order to understand the mechanism of drug release, the in vitro release experiments of inclusion compounds and drug loaded microspheres were carried out by simulating the pH values of human stomach, intestine and blood. The results show that 尾 -CDPH and LA can form 1:1 molar ratio inclusion complex, the average content of LA in inclusion complex can reach (27 鹵1.1), and the solubilization amount of LA can reach 11978mg / L, which is 3.9 times that of LA- 尾 -CD inclusion complex and 1.5 times of that of LA- 尾 -CD inclusion complex. The release of polymer inclusion complexes in vitro showed that the drug release could reach 8 hours in simulated blood pH environment. The optimum conditions for the preparation of drug-loaded microspheres by soaking and loading are as follows: the concentration of solvent ethanol in the reaction is 70 and the soaking temperature of the drug loaded microspheres is 45 鈩，

本文編號(hào)：2257554