本文選題：紫杉醇 + 納米脂質(zhì)體�。� 參考：《浙江大學》2014年碩士論文

【摘要】：目的：探討紫杉醇納米脂質(zhì)體凝膠劑的制備方法、體外評價及其對大鼠角叉菜膠致足腫脹模型及小鼠甲醛致痛模型的鎮(zhèn)痛抗炎作用,以期為紫杉醇開發(fā)成治療類風濕性關(guān)節(jié)炎的新制劑奠定實驗基礎(chǔ)。方法：1、建立紫杉醇的HPLC色譜分析法,以及紫杉醇納米脂質(zhì)體包封率的測定方法。2、采用薄膜分散高壓微射流法制備紫杉醇納米脂質(zhì)體,冷凍干燥至粉末狀,以包封率、粒徑為指標采用正交試驗篩選最佳工藝。采用透射電鏡和納米粒徑測定儀觀測其形態(tài),粒徑大小及分布。3、以粘度、基質(zhì)色澤、涂展性及均勻度為觀察指標,確定紫杉醇納米脂質(zhì)體凝膠劑最佳基質(zhì),以累積釋放量為指標采用正交試驗篩選最佳工藝。制備紫杉醇納米脂質(zhì)體凝膠劑并考察其體外穩(wěn)定性。采用透析膜擴散法進行體外釋放試驗,以離體小鼠皮結(jié)合改良Franz擴散裝置考察其體外透皮特性以及藥物在小鼠皮膚中的分布情況。4、進一步考察紫杉醇納米脂質(zhì)體凝膠劑的皮膚刺激性、過敏反應及對小鼠甲醛致痛模型及大鼠角叉菜膠致足腫脹模型的鎮(zhèn)痛抗炎作用。結(jié)果：1、建立了簡單可行,操作簡便的HPLC色譜法,用于測定紫杉醇。確定了紫杉醇納米脂質(zhì)體包封率的測定方法。2、確定紫杉醇納米脂質(zhì)體的最佳工藝為：卵磷脂含量為2%,藥物與磷脂質(zhì)量比為1：30,磷脂與膽固醇的質(zhì)量比為10：1。采用最佳處方工藝制得的脂質(zhì)體粒徑為81.8nm；粒徑分布系數(shù)為0.18；平均包封率73.2%。通過透射電鏡觀察,納米脂質(zhì)體圓形或類球形,分散性良好,具明顯指紋狀結(jié)構(gòu)。3、通過篩選確定凝膠基質(zhì)為卡波姆,紫杉醇納米脂質(zhì)體凝膠劑的最佳處方：卡波姆3%,甘油5%,透皮滲透劑3%氮酮。72h藥物累積釋放百分率為79.04%；48h的藥物單位面積累積滲透量為429.68μg.cm-2,與紫杉醇凝膠劑比較,脂質(zhì)體能顯著促進紫杉醇透過皮膚(P0.05)。紫杉醇納米脂質(zhì)體給藥4h后在角質(zhì)層和活性皮膚層中的藥物含量分別為3.41μg.cm-2.5.35μg.cm-2,與紫杉醇凝膠劑比較,能顯著提高藥物在皮膚中的滯留量(P0.05)。4、紫杉醇納米脂質(zhì)體用于皮膚后無明顯的刺激作用,與豚鼠皮膚反復接觸后未見過敏反應的發(fā)生。抗炎實驗中,與模型組比較,各給藥組在一定時間內(nèi)均能顯著減輕致炎足爪的腫脹程度(P0.05),并呈現(xiàn)明顯的量效關(guān)系。甲醛致痛實驗中,給藥組與模型組比較,小鼠舔足次數(shù)明顯減少(P0.05)。結(jié)論：該制劑制備工藝簡單,易于涂布,粒徑較小且分布均勻,體外釋放緩慢,具有明顯的緩釋作用,與紫杉醇凝膠劑相比,納米脂質(zhì)體能增加藥物的皮膚滯留量,促進脂溶性藥物紫杉醇透過皮膚并具有明顯鎮(zhèn)痛抗炎作用。
[Abstract]:Objective: to investigate the preparation and in vitro evaluation of paclitaxel nano-liposome gel and its analgesic and anti-inflammatory effects on rat paw swelling induced by carrageenin and formaldehyde-induced pain in mice. In order to lay the experimental foundation for taxol to develop into a new preparation for the treatment of rheumatoid arthritis. Methods HPLC chromatographic analysis of paclitaxel and determination of encapsulation efficiency of paclitaxel nanoliposomes were established. Paclitaxel nanoliposomes were prepared by thin-film dispersion high-pressure micro-jet method. The best technology was selected by orthogonal test. The morphology, size and distribution of paclitaxel nano-liposomes were observed by transmission electron microscope (TEM) and nano-particle size analyzer. The optimum matrix of paclitaxel nano-liposome gel was determined by using viscosity, color and color of matrix, spreading property and uniformity as observation indexes. The best technology was screened by orthogonal experiment with cumulative release amount as index. Paclitaxel nano-liposome gel was prepared and its stability in vitro was investigated. In vitro release test was carried out by dialysate membrane diffusion method. The in vitro transdermal properties and drug distribution in mouse skin were investigated by using an isolated mouse skin and modified Franz diffusion apparatus. The skin irritation of paclitaxel nano-liposome gel was further investigated. Anaphylaxis and its analgesic and anti-inflammatory effects on formaldehyde-induced pain model and rat paw swelling model induced by carrageenin. Results: a simple and convenient HPLC chromatography was established for the determination of paclitaxel. The entrapment efficiency of paclitaxel nanoliposomes was determined as follows: the content of lecithin was 2, the mass ratio of drug to phospholipid was 1: 30, and the mass ratio of phospholipid to cholesterol was 10: 1. The particle size of liposome was 81.8 nm, the particle size distribution coefficient was 0.18, and the average entrapment efficiency was 73.2%. The nano-liposomes were round or globular by transmission electron microscope, and had good dispersibility and obvious fingerprint structure. The gel matrix was determined to be carbomer by screening. The best formulation of paclitaxel nano-liposome gel: carbomer 3um, glycerol 5h, transdermal osmotic agent 3% azone .72h drug cumulative release percentage 79.04g 路cm ~ (-2) per unit area of the drug was 429.68 渭 g 路cm ~ (-2), compared with paclitaxel gel. Lipid can significantly promote paclitaxel through the skin P 0.05. The contents of paclitaxel nanoliposomes in corneum and active skin layer were 3.41 渭 g.cm-2.5.35 渭 g 路cm-2, respectively, which were compared with paclitaxel gel. Paclitaxel nanoliposomes had no obvious stimulative effect on skin, and no allergic reaction occurred after repeated contact with guinea pig skin. In the anti-inflammatory experiment, compared with the model group, each group could significantly reduce the swelling degree of paw in a certain time, and showed a significant dose-effect relationship. In the experiment of formaldehyde-induced pain, compared with the model group, the mice licked their feet significantly. Conclusion: compared with paclitaxel gel, nano-liposomes can increase the skin retention of the drug, with simple preparation process, easy coating, small particle size and uniform distribution, slow release in vitro and obvious slow-release effect. Promote fat-soluble drug paclitaxel through the skin and have obvious analgesic anti-inflammatory effect.
【學位授予單位】：浙江大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R943

【參考文獻】

相關(guān)期刊論文 前1條

1 劉霞;祁兢晶;;5-氟尿嘧啶脂質(zhì)體凝膠劑在兔耳增生性瘢痕中的透皮吸收研究[J];公共衛(wèi)生與預防醫(yī)學;2009年03期

，

本文編號：1940154