结肠靶向泡沫气雾剂的研究

【作者】 杜书君；

【导师】 郝保华；

【作者基本信息】 西北大学 ， 中药学， 2009， 硕士

【摘要】 溃疡性结肠炎是一种原因不明的炎症性疾病,多发于结肠部位。较理想的给药方式是直肠给药,结合泡沫气雾剂喷出的泡沫能在结肠部位均匀涂布,可直接与病变部位接触的特点,本课题拟设计一种治疗结肠炎的新剂型-结肠靶向泡沫气雾剂。本文对自拟处方药材进行处理,筛选剂型的配方,制备出泡沫气雾剂,进而对其结肠定位给药的靶向性、毒理学及药效学进行了研究。得出结论如下:（1）药物处方的拟定及药材处理按涩肠止泻、祛腐生肌、清热解毒的原则拟定处方:五味子、乌梅、白及、连翘和地榆。通过正交试验,得到处方药材的最优提取工艺。白及:加水量为药材的12倍,提取1.5 h,提取3次,乙醇浓度80%;五味子及其它药材:加水量为药材的10倍,提取2 h,提取3次。（2）配方筛选通过泡沫性能考察和体外透粘膜试验得到泡沫气雾剂最优配方:茶皂苷2.0%,白及胶2.0%,丙二醇4.0%和抛射剂15%。配方中白及胶既是治病的活性成分,又是优良的稳泡剂。（3）结肠定位给药靶向性评价利用靶向性评价指标,本文首次通过比较灌胃和直肠给药后血浆与结肠组织液中药物的变化规律,得到评价指标re=4.74,te=4.38,Ce=4.26,表明结肠定位给药泡沫气雾剂具有靶向性。（4）毒理学及药效学研究研究发现小鼠LD₅₀为112.8 g/Kg,药液对结肠粘膜无刺激,并具有较强的止血、止泻和抗炎作用。本文研究的泡沫气雾剂疗效确切,具有靶向性,可作为治疗溃疡性结肠炎的一种新剂型。更多还原

【Abstract】 Ulcerative colitis(UC) is an unknown inflammatory bowel disease which mostly occurs in colon.The way of retention enem is widely used.Considering aerosol foam bubbles can directly contact with the lesion site of colon,aerosol foam was used as a new form to treat ulcerative colitis.In this paper,extracted of herbs,screened of prescription,preparated of aerosol foam are studied.Further more,toxicology and pharmacodynamics are discussed.The results are as follows:(1)Determinating prescription of drug and Extracting herbsThe development of prescription based on the rules of muscle growing and carrion removing,heat clearing and toxicity lifting,Shibuya intestines and diarrhea.The orthogonal test was used to optimize the extraction process of prescription drugs.The optimize extract process of gum bletilla was as follows:adding twenty-six times amount of water,decoting for three times,extracting for half past one hours each time,and alcohol concentration is 70%in the processing of alcohol-precipitation.The optimize extract process of fructus Schisandra chinensiswas as follows:fructus Schisandra chinensiswas were extracted by water cooking for three times with volume ten and cooking for two hours each time.(2)Selecting of prescriptivesWe get the optimal prescriptives of aerosol foam by researching the performance of bubbles and testing permeability of mucosal in vitro:tea saponin 2.0%,gum bletilla 2.0%, propylene glycol 4.0%and 15%of projectile agent.Besides,gum bletilla is the active ingredient of curing disease and also a good foam stabiliter.(3)Evaluating the targeting effect of Colon-specific drug deliveryThe first time,we obtained the changing rule of drug delivery by comparing the concentration in plasma and the fluid of colon tissue.We acquired the evaluation index of targeting effect are as follows:re=4.74,te=4.38,Ce=4.26.(4)Toxicology and pharmacodynamicsThrough the studies we found:the Median lethal dose is 112.8 g/Kg,without stimulation on the colonic mucosa,a strong bleeding,diarrhea and anti-inflammatory effects.This test shows that the aerosol foam can be used as a new form for the treating of ulcerative colitis.更多还原