本文選題：阿霉素　切入點：殼聚糖　出處：《新鄉(xiāng)醫(yī)學院》2014年碩士論文

【摘要】：背景微膠囊技術已經(jīng)在許多領域得到了廣泛應用,可以掩蓋藥物的不良氣味及口味、提高藥物的穩(wěn)定性、減少藥物對胃的刺激、包裹生物活性物質等。常用的微囊化方法有物理化學法、物理機械法、化學法等。本課題選用殼聚糖為囊材、阿霉素為模型藥物。殼聚糖不僅來源廣泛,天然無毒,還具有優(yōu)良的成膜性能,具備控制膽固醇、預防和控制高血壓、抑制細菌活性、抗腫瘤等特性。阿霉素為廣譜抗腫瘤藥,具有強烈的細胞毒性作用,抑制RNA能力最強,在腫瘤內(nèi)科治療中發(fā)揮著重要的作用,但因其毒性大,患者耐受性差,而將其微囊化后不僅可以降低毒性,而且可以提高藥物的穩(wěn)定性及生物利用度。 目的本課題擬通過制備殼聚糖載阿霉素微囊,研究其體外釋放機理及藥效學,為以殼聚糖為載體的藥物微囊化的基礎應用研究提供理論支持和實驗基礎。 方法本課題首先采用高效液相色譜法建立了阿霉素的含量測定方法,通過Minitab對實驗進行響應曲面設計和優(yōu)化,運用單凝聚法制備了殼聚糖載阿霉素微囊。對每批所制微囊的外觀形貌和粒徑分布進行表征；通過所建立的含量分析方法,計算其載藥量和包封率；通過體外釋放實驗測定累積釋放率。研究過程中,通過對殼聚糖載藥微囊成囊及體外釋放機理的研究,以評估各種相關因素的影響；以荷有H22肝癌細胞小鼠為腫瘤模型對載藥微囊進行藥效學的初步研究。 結果1.采用高效液相色譜法建立了阿霉素的含量測定方法,經(jīng)方法學驗證,表明阿霉素在1.01-50.4μg·ml-1濃度范圍內(nèi)具有良好的線性關系。 2.阿霉素-殼聚糖微囊制備優(yōu)化條件為殼聚糖質量濃度0.2%、芯壁比2：3、表面活性劑含量7%及溫度45℃；微囊的平均粒徑為12.51±1.26μm,跨距為0.65；平均載藥量(%)20.6±0.21,包封率(%)90.73±0.40。微囊質量均符合中國藥典2010年版微囊制備的參數(shù)要求。 3.實驗結果表明,殼聚糖的性質、微囊的粒徑、交聯(lián)劑的用量、緩釋介質環(huán)境等因素對于微囊的體外釋放產(chǎn)生不同的影響。 4.實驗結果表明,ADM微囊化后抑瘤效果更優(yōu),不僅延長了ADM作用時間,同時降低了其相對的脾和胸腺毒性,從而實現(xiàn)了長效、低毒的治療目的。 結論本課題以ADM為模型藥物,CS為囊材,所制得微囊擁有良好的緩釋特性,并且可在顯著提高抑瘤率的同時,降低ADM的毒副作用。
[Abstract]:Background Microencapsulation technology has been widely used in many fields, which can cover up the bad smell and taste of drugs, improve the stability of drugs, reduce the irritation of stomach, encapsulate bioactive substances and so on.The commonly used microencapsulation methods include physicochemical method, physico-mechanical method, chemical method and so on.Chitosan was selected as capsule material and adriamycin as model drug.Chitosan not only has a wide range of sources, natural non-toxic, but also has excellent film forming properties, such as cholesterol control, prevention and control of hypertension, inhibition of bacterial activity, anti-tumor and other characteristics.Adriamycin is a broad-spectrum antitumor drug with strong cytotoxicity and the strongest ability to inhibit RNA, which plays an important role in the treatment of oncology.Microencapsulation can not only reduce the toxicity, but also improve the stability and bioavailability of the drug.Objective to prepare chitosan-loaded doxorubicin microcapsules and study their release mechanism and pharmacodynamics in vitro to provide theoretical and experimental basis for the basic application of chitosan-based drug microencapsulation.Methods A method for the determination of adriamycin was established by high performance liquid chromatography (HPLC). The response surface of the experiment was designed and optimized by Minitab. Chitosan loaded doxorubicin microcapsules were prepared by single agglomeration method.The appearance and particle size distribution of each batch of microcapsules were characterized, the drug loading and encapsulation efficiency were calculated by the established method, and the cumulative release rate was determined by in vitro release experiment.In order to evaluate the influence of various related factors, the pharmacodynamics of drug loaded microcapsules in mice bearing H22 was studied by studying the mechanism of microencapsulation and in vitro release mechanism of chitosan loaded microcapsules.Result 1.A method for the determination of adriamycin was established by HPLC. The method was verified that the linear range of adriamycin was 1.01-50.4 渭 g ml-1.2.The optimum conditions for preparation of doxorubicin chitosan microcapsules were as follows: chitosan concentration 0.2, core / wall ratio 2: 3, surfactant content 7% and temperature 45 鈩，

本文編號：1724825