本文選題：超臨界二氧化碳 + 鏈轉(zhuǎn)移劑　； 參考：《東南大學(xué)》2016年碩士論文

【摘要】：研究發(fā)現(xiàn)紫杉醇對于多種癌癥具有很好的治療效果,但是紫杉醇藥物的水溶性極差,這一缺陷限制了其在臨床上的應(yīng)用。目前發(fā)現(xiàn)兩親嵌段聚合物膠束可以增強(qiáng)紫杉醇藥物的水溶性。有機(jī)溶劑揮發(fā)法是制備該膠束的經(jīng)典方法之一,但采用這一制備法制得的膠束中不可避免殘留的有機(jī)溶劑可能對人體產(chǎn)生一定的危害。為此,本論文開發(fā)出一種新的無污染綠色環(huán)保的方法-超臨界二氧化碳揮發(fā)法制備聚合物膠束,并在兩親嵌段聚合物的合成、聚醋酸乙烯酯在超臨界二氧化碳中的相行為、膠束制備、膠束的表征等方面開展了系統(tǒng)的研究工作。本論文合成了三種可逆加成-斷裂鏈轉(zhuǎn)移(RAFT)鏈轉(zhuǎn)移劑,用紅外吸收光譜、核磁共振氫譜確認(rèn)了產(chǎn)物的結(jié)構(gòu),用合成出的三種鏈轉(zhuǎn)移劑誘導(dǎo)醋酸乙烯酯單體的聚合。研究發(fā)現(xiàn)：以乙醇、二硫化碳、氫氧化鉀和2-溴丙酸乙酯為原料制備的黃原酸鹽鏈轉(zhuǎn)移劑對醋酸乙烯酯單體的聚合起促進(jìn)作用,并成功制備了聚醋酸乙烯酯。本文對醋酸乙烯酯單體的聚合條件進(jìn)行優(yōu)化,探究了反應(yīng)溫度、反應(yīng)時(shí)間、鏈轉(zhuǎn)移劑與引發(fā)劑摩爾比對醋酸乙烯酯聚合的影響。用凝膠色譜(GPC)測試了聚合物的分子量及其分子量分布。測試了所合成的窄分子量分布的聚醋酸乙烯酯在不同溫度和壓力下二氧化碳中的濁點(diǎn)壓力,結(jié)果表明聚醋酸乙烯酯具有較強(qiáng)的親超臨界二氧化碳性。利用制得的聚醋酸乙烯酯作為大分子鏈轉(zhuǎn)移,聚乙二醇甲基丙烯酸酯(PEGMA)為親水單體,成功制備出兩親嵌段聚合物聚醋酸乙烯酯-b-聚乙二醇甲基丙烯酸酯(PVAc-b-PEGMA),并將制備的兩親嵌段聚合物采用有機(jī)溶劑揮發(fā)法和超臨界二氧化碳揮發(fā)法制備聚合物膠束。用芘熒光探針技術(shù)測試了聚合物的臨界膠束濃度(CMC),其臨界膠束濃度值為33.88 mg/L。用透射電鏡(TEM)對膠束的形貌進(jìn)行了觀察,兩種方法制備的膠束都呈現(xiàn)均一的球狀結(jié)構(gòu)。動態(tài)光散射(DLS)測試了膠束的粒徑及粒徑分布,超臨界二氧化碳揮發(fā)法制備所得膠束的平均粒徑要比有機(jī)溶劑揮發(fā)法制備所得膠束的平均粒徑要大,其平均粒徑為476 nm。利用紫外-可見見光光譜對膠束的載藥能力進(jìn)行了測試,超臨界二氧化碳揮發(fā)法制備的膠束載藥量和包封率要比有機(jī)溶劑揮發(fā)法制備所得膠束的載藥量和包封率高,其載藥量和包封率分別為12.7%和38.1%。通過對膠束性能的表征,說明本文制備的兩親嵌段聚合物可用于超臨界二氧化碳揮發(fā)法制備膠束,其制備過程中只需超臨界二氧化碳和水,對環(huán)境無污染,具有較好的發(fā)展前景。
[Abstract]:Paclitaxel has been found to be effective in the treatment of many cancers, but the poor water solubility of paclitaxel drugs limits its clinical application. Amphiphilic polymer micelles have been found to enhance the solubility of paclitaxel drugs. The organic solvent volatilization method is one of the classical methods to prepare the micelle, but the residual organic solvent in the micelle prepared by this method may be harmful to the human body. In this paper, a new pollution-free green environmental protection method, supercritical carbon dioxide volatilization method, was developed to prepare polymer micelles, and to synthesize amphiphilic block polymers and the phase behavior of polyvinyl acetate in supercritical carbon dioxide. The preparation of micelles and the characterization of micelles have been studied systematically. In this paper, three reversible addition-break chain transfer agents (RAFTs) were synthesized. The structure of the products was confirmed by IR and NMR spectra, and the polymerization of vinyl acetate monomer was induced by the three chain transfer agents. It was found that the xanthate chain transfer agent prepared from ethanol, carbon disulfide, potassium hydroxide and ethyl 2-bromopropionate played an important role in the polymerization of vinyl acetate monomer, and the polyvinyl acetate was prepared successfully. The polymerization conditions of vinyl acetate monomer were optimized. The effects of reaction temperature, reaction time and molar ratio of chain transfer agent to initiator on the polymerization of vinyl acetate were investigated. The molecular weight and molecular weight distribution of the polymer were measured by gel chromatography (GPC). The cloud point pressure of the synthesized polyvinyl acetate with narrow molecular weight distribution in carbon dioxide at different temperatures and pressures was measured. The results show that the polyvinyl acetate has a strong supercritical carbon dioxide affinity. Poly (vinyl acetate) was used as macromolecular chain transfer and polyethylene glycol methacrylate (PEGMA) as hydrophilic monomer. The amphiphilic block polymer poly (vinyl acetate) -b-polyethylene glycol methacrylate (PVAc-b-PEGMAA) was successfully prepared. The amphiphilic block polymers were prepared by organic solvent volatilization and supercritical carbon dioxide volatilization. The critical micelle concentration (CMC) of the polymer was measured by pyrene fluorescence probe technique. The critical micelle concentration was 33.88 mg 路L ~ (-1) 路L ~ (-1). The morphology of the micelles was observed by TEM and TEM. The micelles prepared by the two methods showed uniform spherical structure. The particle size and particle size distribution of micelles were measured by DLSs. The average particle size of micelles prepared by supercritical carbon dioxide volatilization method was larger than that prepared by organic solvent volatilization method, and the average particle size was 476 nm. The drug loading capacity of micelles prepared by supercritical carbon dioxide volatilization method is higher than that prepared by organic solvent volatilization method, and the drug loading capacity and encapsulation efficiency of micelles prepared by supercritical carbon dioxide volatilization method are higher than those prepared by organic solvent volatilization method. The drug loading and entrapment efficiency were 12.7% and 38.1%, respectively. The amphiphilic block polymers prepared in this paper can be used in the preparation of micelles by supercritical carbon dioxide volatilization method, and only supercritical carbon dioxide and water are required in the preparation process, so there is no pollution to the environment. It has a good development prospect.
【學(xué)位授予單位】：東南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：TQ460.4;O631.5

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