本文選題：超臨界反溶劑 + 藥物輸送系統(tǒng)��； 參考：《華南理工大學》2010年碩士論文

【摘要】： 紫杉醇是臨床上最有效的抗癌藥物之一,但水溶性極低,且在大多數(shù)醫(yī)用溶媒中不溶解或者溶解度較低,現(xiàn)行制劑以無水乙醇和聚乙烯基蓖麻油(v/v,50/50)混合物為溶劑,具有很大的毒副作用。因此,紫杉醇新劑型的研制成為熱點。超臨界反溶劑(Supercritical anti-solvent, SAS)法通過預設不同的操作參數(shù),可有效控制藥物輸送系統(tǒng)(Drug delivery system,DDS)微粒的粒徑及其分布,是低溶劑殘留的DDS綠色制備新技術。本論文以紫杉醇為模型藥物,研究各過程參數(shù)對SAS法制備DDS的影響。 本文通過單因素實驗,以DCM/無水乙醇(EtOH)、DCM/二甲亞砜(DMSO)混合溶液為溶劑,采用SAS法成功制備出紫杉醇DDS微粒;借助掃描電鏡(SEM)、激光粒度儀和高效液相色譜等檢測手段對DDS微粒進行表征,考察了混和溶劑體系下,過程參數(shù)包括壓力、溫度、溶劑配比、溶液流速和溶質濃度等對DDS微粒的形貌、粒徑和包封率的影響。 結果表明,所得紫杉醇DDS微粒的形貌受溶劑性質影響較大,在DCM中加入EtOH有助于改善DDS微粒的表面光滑程度;而當加入DMSO時DDS微粒出現(xiàn)孔狀結構,且分散度較差。在實驗范圍內,增加壓力(80-140bar),所得DDS微粒的粒徑和包封率增加;增加溫度(30-45℃),所得DDS微粒的粒徑呈上升趨勢。在DCM/EtOH體系中,DDS微粒包封率隨溫度升高而增加,而在DCM/DMSO溶劑體系中,包封率隨溫度升高先增加后降低;當溫度高于40℃時,微粒之間聚集,甚至形成膜狀物質。樣品溶液流速增大DDS微粒的平均粒徑隨之增大。當載體聚乳酸(PLLA)與PTX濃度之比為5:1時,獲得DDS微粒的包封率較高為86.8%。 上述研究工作可為SAS法成功制備DDS微粒提供參考。
[Abstract]:Paclitaxel is one of the most effective anticancer drugs in clinic, but its water solubility is very low, and it is insoluble or low solubility in most medical solvent. Have great toxic side effects. Therefore, the development of a new dosage form of paclitaxel has become a hot spot. Supercritical antisolvent supercritical anti-solvent (Sass) method can effectively control the particle size and distribution of drug delivery system by preset different operating parameters. It is a new green preparation technique for low solvent residual DDS. In this paper, paclitaxel was used as model drug to study the effect of various process parameters on the preparation of DDS by SAS method. In this paper, paclitaxel DDS particles were successfully prepared by SAS method in the mixed solution of DCM/ anhydrous ethanol (et OHH) and DMSO (dimethyl sulfoxide) as solvent. DDS particles were characterized by scanning electron microscope (SEM), laser particle size analyzer and high performance liquid chromatography (HPLC). The process parameters including pressure, temperature and solvent ratio were investigated in the mixed solvent system. The effects of solution flow rate and solute concentration on the morphology, particle size and encapsulation efficiency of DDS particles. The results show that the morphology of the obtained DDS particles is greatly affected by the solvent properties, and the addition of EtOH to DCM can improve the surface smoothness of DDS particles, while when DMSO is added, the pore structure of DDS particles is observed, and the dispersion of DDS particles is poor. In the range of experiment, the particle size and encapsulation efficiency of DDS particles increased with the increase of pressure (80-140), and the particle size of DDS particles increased with the increase of temperature from 30 鈩，

本文編號：1896813