本文關(guān)鍵詞：噴霧干燥法制備脊髓灰質(zhì)炎微球減毒活疫苗　出處：《中國協(xié)和醫(yī)科大學(xué)》2009年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 脊髓灰質(zhì)炎病毒 微球 噴霧干燥 正交試驗

【摘要】： 目前,在疫苗保存方面常常采用冷凍干燥技術(shù),最近出現(xiàn)一種新的疫苗保存技術(shù),即,噴霧干燥技術(shù)。噴霧干燥是流化技術(shù)用于液態(tài)物料干燥的一種較好的方法。其基本原理是利用霧化器將一定濃度的液態(tài)物料,噴射成霧狀液滴,落于一定流速的熱氣流中,使之迅速干燥,獲得粉狀或顆粒狀制品。該技術(shù)一直被認為在研制疫苗氣霧制劑方面有替代冷凍干燥的潛能。噴霧干燥法不僅能通過一步法得到特殊形貌和大小的疫苗微球,還極大的降低了疫苗除水的成本,尤其適用于大規(guī)模疫苗工業(yè)生產(chǎn)。在疫苗除水分保存方面,噴霧干燥法比冷凍干燥法更迅速、成本更低。 噴霧干燥過程可以分為三個部分: 1)霧化器將一定濃度的液態(tài)物料,噴射成霧狀液滴; 2)液滴落于干燥室一定流速的熱氣流中,迅速干燥; 3)體系的旋風(fēng)將粉狀或顆粒狀制品迅速收集到收集瓶里。 盡管噴霧干燥機的溫度比常溫高,但同向(空氣和進樣品口進入干燥室是同一個方向)噴霧干燥機能用于干燥熱敏性材料。在液滴干燥過程中,液滴的溫度達不到顯示的入口溫度。因為熱氣流的熱量用于蒸發(fā)流體里的水份,而不是加熱液滴,當流體里的水份被蒸發(fā)干時,干燥的顆粒才對熱敏感。體系里的快速旋風(fēng)將干燥的顆�？焖俚氖占绞占坷�,避免了樣品熱失活。 目前國外有報道通過噴霧干燥法制備熱敏感的蛋白類物質(zhì)氣霧劑。通常,在蛋白液體進行噴霧干燥前加入穩(wěn)定的賦形劑,可以防止蛋白在噴霧干燥和保存過程中失活。研究者認為不穩(wěn)的材料被固定成玻璃態(tài)有利于活性的保持。二糖是用得最多的賦形劑,其中海藻糖的效果最好。然而,聚乙烯吡咯烷酮polyvinylpyrrolidone(PVP)能防止噴霧干粉制劑里的賦形劑糖類的重結(jié)晶,降低在保存過程中干燥粉劑的重結(jié)晶導(dǎo)致的失活率。人血清白蛋白(HSA)在冷凍干燥和噴霧干燥中也被用于降低粉劑的結(jié)晶化的賦形劑。通過檢測樣品的玻璃化溫度可以評價樣品的抗結(jié)晶化能力,玻璃化轉(zhuǎn)變溫度是樣品從玻璃態(tài)向橡膠態(tài)轉(zhuǎn)變或低分子活性到高分子活性的轉(zhuǎn)變(即,容易結(jié)晶化)。 聚乙烯吡咯烷酮和白蛋白是已經(jīng)被證實的能提高樣品玻璃化轉(zhuǎn)化溫度的賦形劑,從而提高樣品存放的溫度,增強了樣品的穩(wěn)定性。干燥樣品中的水分會增加分子間的流動性,降低了玻璃化溫度,因此疫苗吸入劑的開發(fā),選擇不易吸水的賦形劑顯得尤為重要。 在我們的研究中,采用噴霧干燥法制備脊髓灰質(zhì)炎減毒活疫苗。以正交試驗法篩選最佳保護劑配方以及最佳工藝條件,通過樣品的含水量、形態(tài)、病毒滴度、粒徑大小分布和熱力學(xué)性質(zhì)等特性評價疫苗的穩(wěn)定性。最佳噴霧干燥工藝為:入口風(fēng)溫180℃、入口風(fēng)壓3.9m/s、進樣速度2.5ml/min、保護劑配方是1.5%海藻糖+0.2%hominine serumalbumin(HSA)+0.2%olyvinylpyrrollidone(PVP)(w/v)。微球球形完整,分散性好,平均粒徑為10.9μm,產(chǎn)率為54.25%,噴霧后、37℃放置一周和25℃保存6個月病毒的滴度下降不高于0.5LgCCID_(50)/ml。以生物降解材料海藻糖、PVP、HSA通過噴霧干燥法制備的微球疫苗穩(wěn)定性好,工藝簡便,易于工業(yè)化生產(chǎn)。
[Abstract]:The invention relates to a spray drying method which can obtain vaccine microspheres with special appearance and size by a one - step method , and is especially suitable for industrial production of large - scale vaccines . the spray drying process can be divided into three parts : 1 ) the atomizer sprays a certain concentration of liquid material into atomized liquid droplets ; 2 ) the liquid drops fall into the hot air flow at a certain flow rate in the drying chamber , and the liquid drops rapidly ; and 3 ) the cyclone of the system quickly collects the powdery or granular products into the collection bottle . The temperature of the spray dryer is higher than normal temperature , but the same direction ( the air and sample inlet enters the drying chamber is the same direction ) and the spray drying function is used for drying the heat - sensitive material . During the drying process of the liquid drops , the temperature of the liquid drops can not reach the displayed inlet temperature . Because the heat of the hot gas stream is used for evaporating water in the fluid rather than heating the liquid drops , the dried particles are sensitive to heat when the water in the fluid is evaporated to dryness . in general , stable excipients are adde prior to spray drying of that protein liquid to prevent inactivation of proteins in spray drying and preservation . polyvinylpyrrolidone and albumin are proved to be an excipient capable of improving the glass transition temperature of the sample so as to improve the storage temperature of the sample and enhance the stability of the sample . In our study , the stability of vaccine was evaluated by spray - drying method to prepare attenuated live vaccine . The best spray drying process was as follows : inlet wind temperature 180 鈩，

本文編號：1356305