本文選題：黃芩苷 + 類脂納米囊�。� 參考：《山東大學》2014年碩士論文

【摘要】：黃芩苷(baicalin,BA)是從唇形科植物黃芩(Scutellaria baicalensis Georgi)干燥根中提取的一種黃酮類化合物。具有抗菌、抗炎、抗氧化、抗病毒、擴張血管、調(diào)節(jié)免疫系統(tǒng)等藥理作用,在惡性腫瘤、傳染病、延緩人體衰老等方面的應用前景非常廣闊。黃芩苷在藥理安全性、成本效益、毒性等方面的優(yōu)勢,促使許多研究人員對其進行了深入研究。 黃芩苷為難溶性藥物,在水中溶解度較小,在堿性條件下易溶解,在酸性溶液中易析出,對光不穩(wěn)定,且口服生物利用度低,限制了其推廣使用。為此,藥劑研究者在黃芩苷的制劑方面進行了大量的探索和研究。為改善其口服吸收,本文制備黃芩苷類脂納米囊(baicalin-lipid nanocapsules, BA-LNC),考察了其理化性質(zhì),并進行了大鼠口服給藥動力學的研究,探索類脂納米囊作為黃芩苷口服給藥載體的可能性及優(yōu)勢。 用相轉(zhuǎn)化法制備類脂納米囊,以包封率和載藥量為指標,通過單純形網(wǎng)格法對處方因素進行優(yōu)化,采用響應面法對實驗結(jié)果進行處理,得到最優(yōu)處方為：黃芩苷用量為10mmg,卵磷脂的用量為3Omg,NaCl的用量為34mg,油相、表面活性劑、水三種組分總量為1.97g,其中表面活性劑聚乙二醇單硬脂酸酯(SolutolHS15)的質(zhì)量百分比為38%,油相辛酸/癸酸三甘油酯(MCT)的質(zhì)量百分比為12%,蒸餾水的質(zhì)量百分比為50%。實驗結(jié)果表明制備的黃芩苷類脂納米囊包封率為92.58%,載藥量為1.69%。在透射電鏡下BA-LNC呈類球形,分散良好,無粘連,平均粒徑為84.2nm,多分散指數(shù)為0.201,Zeta電位為-13.2mV。通過透析法考察了BA-LNC在模擬胃、腸液中的體外釋藥行為,結(jié)果表明制劑在人工胃液及人工腸液中均表現(xiàn)出一定的緩釋性,且后者相對前者釋放較快。 采用Wistar大鼠研究黃芩苷類脂納米囊制劑的口服藥物動力學,結(jié)果顯示：BA-LNC制劑相對于黃芩苷混懸液(對照組)在AUC0-12、AUC0-∞、MRT0-12、 MRT0-∞等藥動學參數(shù)上有明顯優(yōu)勢,說明BA-LNC制劑可促進藥物的吸收,延長黃芩苷在體內(nèi)的滯留時間,從而提高黃芩苷的口服生物利用度。
[Abstract]:Baicalin (Baicalinba) is a flavonoid extracted from dried roots of Scutellaria baicalensis Georgi. With antibacterial, anti-inflammatory, anti-oxidation, anti-virus, vasodilation, regulating the immune system and other pharmacological effects, in malignant tumors, infectious diseases, delaying human aging and other aspects of the application prospects are very broad. The advantages of baicalin in pharmacological safety, cost-effectiveness and toxicity have prompted many researchers to study it in depth. Baicalin is difficult to dissolve in water, easy to dissolve in alkaline condition, easy to precipitate in acid solution, unstable to light, and low in oral bioavailability, which limits its popularization and application. To this end, pharmaceutical researchers in the preparation of baicalin carried out a lot of exploration and research. In order to improve the oral absorption of baicalin, baicalin nanoparticles (BA-LNC) were prepared, their physical and chemical properties were investigated, and the kinetics of oral administration of baicalin was studied. Lipid-like nanocysts were prepared by phase inversion method. The encapsulation efficiency and drug load were taken as indexes. The prescription factors were optimized by simplex mesh method and the experimental results were processed by response surface method. The optimum formulation was as follows: baicalin was 10mmg, lecithin was 3Omg NaCl, oil phase, surfactant, and so on. The total content of three components of water is 1.97 g. The mass percentage of surfactant polyglycol monostearate (Soluto HS15) is 38. The mass percentage of oil phase octanoic acid / triglyceride decanoate (MCT) is 12 and that of distilled water is 50. The results showed that the encapsulation efficiency of baicalin nanoparticles was 92.58 and the drug load was 1.69. Under transmission electron microscope, BA-LNC was spherical with good dispersion and no adhesion. The average particle size was 84.2 nm, and the polydispersity index was -13.2 MV. The in vitro release behavior of BA-LNC in simulated stomach and intestinal fluid was investigated by dialysis. The results showed that BA-LNC showed a certain sustained release in artificial gastric juice and artificial intestinal fluid, and the latter released more quickly than the former. The oral pharmacokinetics of baicalin lipid nanocysts in Wistar rats was studied. The results showed that compared with baicalin suspension (control group), the oral pharmacokinetics of baicalin was significantly superior to that of baicalin suspension (control group) in the pharmacokinetic parameters such as AUC0-12 AUC0- 鈭，

本文編號：2079484