本文選題：高血壓 + 絲素蛋白　； 參考：《重慶理工大學(xué)》2014年碩士論文

【摘要】：作為“富貴病”之一的高血壓，是一種常見的心血管疾病，發(fā)病率呈逐年升高的趨勢，對人體的心臟、腦、腎等重要器官造成損傷，嚴(yán)重威脅人類的健康。而高血壓的治療除了運(yùn)動和食療等非藥物治療外，只能依靠藥物來治療。而目前臨床上對于高血壓的治療，僅能做到控制其發(fā)展，難以根治，這就決定了高血壓患者一般需要長期服藥。但長期服藥會導(dǎo)致不良反應(yīng)增多，副作用加強(qiáng)，因此對于高血壓藥物緩釋制劑的研究越來越多。 本課題在團(tuán)隊前期研究的基礎(chǔ)上，巧妙的結(jié)合具緩釋能力的納米絲素蛋白和具備自組裝能力的微米絲素蛋白，對高血壓藥物進(jìn)行包裹、干燥、壓片制備出載藥緩釋制劑用材料。對其的緩釋能力、毒性及等進(jìn)行了相關(guān)的研究。 首先，分別制備出材料納米絲素蛋白/聚乙烯醇/聚乙二醇（SFP/PVA/PEG）和SF/C2H5OH/(卡托普利)；然后，將二者依比例在一定的條件下結(jié)合制備出高血壓藥物緩釋制劑用材料。對其進(jìn)行宏觀形貌、紫外光譜UV、紅外光譜FTIR、掃描電鏡SEM等表征研究，結(jié)果顯示：藥物緩釋材料質(zhì)量差異小、均一，成功制備出的藥片具有潛在的緩釋能力（具備較大的孔洞或縫隙）。衍生化分光光度法在409nm對卡托普利含量進(jìn)行測定，其標(biāo)準(zhǔn)曲線呈現(xiàn)良好的相關(guān)性，并以此來研究其體外釋藥，結(jié)果顯示：相比于市售的卡托普利片，自制的卡托普利片釋放片在模擬胃、腸液中釋放緩慢，均符合緩釋制劑的動力學(xué)方程（Peppas釋放動力學(xué)），適合開發(fā)為緩釋制劑；釋放后的藥片具有均一孔洞，大小為1μm-10μm，推測其釋放的機(jī)制應(yīng)該是擴(kuò)散或者擴(kuò)散、溶蝕的共同作用。細(xì)胞毒性試驗研究顯示，細(xì)胞生長良好，緩釋材料的浸提液及釋放液等細(xì)胞毒性評級均為0級或1級，在安全范圍內(nèi)，未構(gòu)成細(xì)胞毒性，符合生物材料細(xì)胞相容性要求；全身急性毒性、亞急性全身毒性研究發(fā)現(xiàn)，籠邊觀察、體重相對增長率、臟器系數(shù)、大體病理學(xué)檢查等觀察結(jié)果均無異常，，顯示其無毒，符合醫(yī)療器械生物安全評價標(biāo)準(zhǔn)。 研究結(jié)果表明，制備出的普通高血壓藥物緩釋制劑用材料具備良好的緩釋能力，且安全無毒，具有廣闊的應(yīng)用前景。
[Abstract]:As one of the "rich and noble diseases", hypertension is a common cardiovascular disease, the incidence of which is increasing year by year, which causes damage to human heart, brain, kidney and other important organs, and seriously threatens human health. The treatment of hypertension, in addition to exercise and diet therapy and other non-drug treatment, can only rely on drugs to treat. At present, the treatment of hypertension can only control its development, which is difficult to cure, which determines that patients with hypertension generally need long-term medication. But long-term medication will lead to more adverse reactions and side effects, so there are more and more studies on sustained release of hypertension drugs. On the basis of the team's previous research, the drug delivery materials for sustained-release preparation were prepared by combining nano-silk fibroin with sustained release and micron silk fibroin with self-assembly ability to encapsulate, dry, and press tablets. The slow release ability, toxicity and so on were studied. Firstly, nano-silk fibroin / polyvinyl alcohol / polyethylene glycol (SFP / PVA / PEG) and SFP / C2H / H / (captopril) were prepared, respectively. The macroscopic morphology, UV spectrum, FTIR, scanning electron microscopy (SEM) and so on were studied. The results showed that the quality difference of drug sustained-release materials was small and uniform. The successfully prepared tablets have potential slow-release capacity (large holes or gaps). The content of captopril was determined by derivatization spectrophotometry at 409nm. The standard curve of captopril showed a good correlation, and the drug release in vitro was studied. The results showed that compared with the captopril tablets sold on the market, The release of captopril tablets in the simulated stomach and intestinal fluid was slow, which was consistent with the kinetics equation of the sustained-release preparations and was suitable for development as a sustained-release preparation. The size is 1 渭 m ~ 10 渭 m, and the mechanism of its release should be diffusion, diffusion and dissolution. The cytotoxicity test showed that the cells grew well, and the cytotoxicity ratings of the extractions and release solutions of the slow-release materials were both grade 0 or grade 1, which did not constitute cytotoxicity within the safe range, and met the requirements of the cytocompatibility of the biomaterials. The study of systemic acute toxicity and subacute systemic toxicity found that the observation results of cage side observation, relative growth rate of body weight, organ coefficient and gross pathology were not abnormal, which showed that they were nontoxic and accord with the standard of biological safety evaluation of medical instruments. The results show that the prepared materials have good sustained-release ability, and are safe and non-toxic, and have a broad application prospect.
【學(xué)位授予單位】：重慶理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R943;R96

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