本文選題：阿苯達(dá)唑 + 殼聚糖　； 參考：《石河子大學(xué)》2014年碩士論文

【摘要】：目的:通過與阿苯達(dá)唑脂質(zhì)體、阿苯達(dá)唑片比較，評(píng)價(jià)阿苯達(dá)唑殼聚糖微球（ABZ-CS-MPs）經(jīng)口服后治療細(xì)粒棘球蚴（E.g）病的療效。 方法:雄性昆明小鼠220只，腹腔接種細(xì)粒棘球蚴，隨機(jī)分成空白對(duì)照組、模型對(duì)照組、口服ABZ-CS-MPs組、口服阿苯達(dá)唑脂質(zhì)體（L-ABZ）組和口服阿苯達(dá)唑片劑組，每組20只。治療組又按口服ABZ37.5mg/(kg·次)、75.0mg/(kg·次)、150.0mg/(kg·次)分成三個(gè)劑量組。所有小鼠飼養(yǎng)12周后開始灌胃給藥，三次/周（每隔一天），連續(xù)治療12周后解剖。評(píng)價(jià)藥物療效包括：E.g大體形態(tài)觀察，囊濕重、囊腫抑制率，E.g病理組織改變，小鼠血液、肝臟中阿苯達(dá)唑主要代謝產(chǎn)物阿苯達(dá)唑亞砜（ABZSX）濃度。 結(jié)果： ABZ-CS-MPs組棘球蚴囊混濁、實(shí)變或鈣化程度較其他治療組明顯。各治療組棘球蚴囊濕重顯著低于對(duì)照組(p0.01), ABZ-CS-MPs組囊腫抑制率較其他給藥組高。棘球蚴生發(fā)層和角質(zhì)層的破壞程度與血液和肝臟濃度變化較一致。ABZ主要代謝產(chǎn)物阿苯達(dá)唑亞砜(ABZSX)的藥物濃度：口服ABZ-CS-MPs37.5mg/kg血漿中為(0.28570.0132)μg/ml,肝臟中為(0.32960.0571) μg/g;75mg/kg組血漿中為(0.82760.3914) μg/mL,肝臟中為(0.44850.3088) μg/g;150mg/kg組血漿中為(0.80120.5021) μg/mL,肝臟中為(0.49590.3013) μg/g。較口服阿苯達(dá)唑片后10h37.5mg/kg血漿中為(0.27680.0164)μg/mL,肝臟中為(0.04160.0188) μg/g;75mg/kg組血漿中為(0.30560.0172) μg/mL,肝臟中為(0.07130.0442) μg/g;150mg/kg組血漿中為(0.40000.0963) μg/mL,肝臟中為(0.04440.0326) μg/g中藥物濃度，均有明顯提高(p0.05)。較口服L-ABZ37.5mg/kg血漿中為(0.30890.0289) μg/mL,75mg/kg組血漿中為(0.33950.0315) μg/mL，150mg/kg組血漿中為(0.42740.1489) μg/mL，有明顯的提高(p0.05)。口服L-ABZ37.5mg/kg肝臟中為(0.13700.1940) μg/g,75mg/kg為(0.78150.4327) μg/g,150mg/kg中為(0.62980.3409) μg/g，與ABZ-CS-MPs比較，無統(tǒng)計(jì)學(xué)意義(p0.05)。 結(jié)論:阿苯達(dá)唑殼聚糖微球可明顯提高阿苯達(dá)唑主要代謝產(chǎn)物阿苯達(dá)唑亞砜在血液及肝臟中的濃度，，有望成為治療包蟲病的一種新的劑型。
[Abstract]:Aim: to evaluate the efficacy of Albendazole chitosan microspheres ABZ-CS-MPs in the treatment of E. granulosus by oral administration, compared with albendazole liposome and albendazole tablets.Methods: 220 male Kunming mice were inoculated intraperitoneally with echinococcus granulosus. They were randomly divided into control group, model control group, oral ABZ-CS-MPs group, albendazole liposome L-ABZ group and albendazole tablet group with 20 rats in each group.The treatment group was divided into three dose groups according to oral ABZ37.5mg/(kg 75. 0 mg / kg.All mice were fed for 12 weeks and were given intragastric administration three times a week (every other day, 12 weeks after continuous treatment).The evaluation of drug efficacy included gross morphological observation, wet weight of capsule, inhibition rate of cysts and pathological changes of E. g, and the concentration of albendazole sulfoxide, the main metabolite of albendazole in blood and liver of mice.Results: the degree of hydatid opacification, consolidation or calcification in ABZ-CS-MPs group was significantly higher than that in other treatment groups.The wet weight of hydatid cyst in each treatment group was significantly lower than that in control group (P 0.01), and the inhibition rate of cyst in ABZ-CS-MPs group was higher than that in other groups.The degree of destruction in the germinal layer and cuticle of echinococcus was consistent with the changes of blood and liver concentrations. The drug concentration of ABZ SX, the main metabolite of ABZ, was 0.28570.0132 渭 g / ml in oral ABZ-CS-MPs37.5mg/kg plasma and 0.32960.0571 渭 g / ml in liver, and 0.82760.3914 渭 g / mL in liver / liver group.0.80120.5021 渭 g / mL in plasma and 0.49590.3013 渭 g / g in liver.Compared with albendazole tablets, the plasma levels of 0.27680.0164 渭 g / mL in 10h37.5mg/kg, 0.04160.01888 渭 g / g / kg in liver, 0.30560.0172渭 g / mL in plasma of 75mg / kg group, 0.07130.0442 渭 g / g / kg / kg group and 0.04440.0326渭 g / g / kg group, respectively, significantly increased the drug concentration in plasma (0.40000.0963渭 g / mL) and 0.04440.0326渭 g / mL in liver.Compared with 0.30890.0289 渭 g / mL 75 mg / kg L-ABZ37.5mg/kg plasma, 0.33950.0315 渭 g / mL / kg plasma was 0.42740.1489 渭 g / mL / kg group (P < 0.05).In oral L-ABZ37.5mg/kg liver, 0.13700.1940) 渭 g / g / kg was 0.78150.4327 渭 g / kg, and 0.62980.3409 渭 g / kg in 150 渭 g / kg L-ABZ37.5mg/kg liver. Compared with ABZ-CS-MPs, there was no significant difference (p 0.05).Conclusion: albendazole chitosan microspheres can significantly increase the concentration of albendazole sulfoxide in blood and liver and may become a new dosage form for the treatment of hydatid disease.
【學(xué)位授予單位】：石河子大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R532.32

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 連文元;何承輝;邢建國;王新春;黃川生;;阿苯達(dá)唑殼聚糖納米粒包封率的測定[J];中國組織工程研究與臨床康復(fù);2011年47期

2 李炳軍;郭淑霞;彭心宇;;包蟲病流行病學(xué)調(diào)查現(xiàn)狀[J];醫(yī)學(xué)綜述;2009年08期

3 彭心宇;肝包蟲病的外科治療新觀點(diǎn)[J];中國實(shí)用外科雜志;2003年11期

4 邵英梅,溫浩;阿苯達(dá)唑脂質(zhì)體治療肝、腹部細(xì)粒棘球蚴病的動(dòng)物實(shí)驗(yàn)研究[J];中國寄生蟲病防治雜志;1998年03期

本文編號(hào)：1752353