【正文】 新一代二氫卟吩類光敏劑的制備與性質(zhì)研究分類號： 學(xué)校代碼： 10574 密級： 學(xué)號： 2007021203 South China Normal University碩士學(xué)位論文題目：二氫卟吩類新型光敏劑的制備與光敏性質(zhì)研究 學(xué)位申請人： 王 君 專業(yè)名稱： 材料物理與化學(xué) 研究方向： 功能材料 所在院系： 化學(xué)與環(huán)境學(xué)院 導(dǎo)師姓名及職稱： 羅一帆 教授 論文提交日期： 2010年6 月 I二氫卟吩類新型光敏劑的制備與光敏性質(zhì)研究二氫卟吩類新型光敏劑的制備與光敏性質(zhì)研究專業(yè)：材料物理與化學(xué) 申請者：王君 導(dǎo)師：羅一帆 教授摘 要本文以我國特有的廉價(jià)蠶沙葉綠素為原料開展了二氫卟吩e二氫卟吩eUF(UF是應(yīng)用二氫卟吩e6和e4及其他物質(zhì)組合得到光敏特性較好的一種復(fù)合新型光敏劑)三種二氫卟吩類新型光敏劑抗腫瘤新藥的制備與光敏性質(zhì)研究工作。主要內(nèi)容與結(jié)論歸納如下：1. 以色譜PLATISIL ODS (5μm ,250mm)對二氫卟吩e6和e4進(jìn)行高效液相色譜法（HPLC）檢測研究。得到二氫卟吩e6的HPLC檢測的最佳色譜條件： 以pH mol/L的醋酸銨—甲醇溶液作為流動相；梯度洗脫條件：甲醇85%（%/min）→100%；流速： mL?min1；檢測波長：407 nm。并對上述方法進(jìn)行了方法學(xué)考察，~，r=，%，%。二氫卟吩e4的HPLC檢測的最佳色譜條件：以pH mol/L的醋酸銨—甲醇溶液作為流動相；梯度洗脫條件：甲醇85%（%/min）→100%；流速： mL?min1；檢測波長：400 nm。并對上述方法進(jìn)行了方法學(xué)考察，~ mg/ml范圍內(nèi)線性良好，r=，%，%。2. 以二氫卟吩e6合成的最佳條件：反應(yīng)體系需隔絕氧氣，并通入氮?dú)?，?40℃回流25min為基礎(chǔ)，成功地進(jìn)行了二氫卟吩e6的增量化合成和純化實(shí)驗(yàn)。得到的產(chǎn)物經(jīng)純化后，二氫卟吩e6的含量均80%；篩選出了最佳萃取條件：萃取時(shí)間為40min，萃取物與萃取劑用量比為1：40；研究了無毒制備二氫卟吩e6的新方法：除去了反應(yīng)中有毒的試劑吡啶和丙酮，用無毒的溶劑乙醇代替了有毒溶劑甲醇。經(jīng)純化后二氫卟吩e6含量80%。通過正交實(shí)驗(yàn)法對二氫卟吩e4合成條件進(jìn)行研究，初步得出了最佳合成條件：160℃、20min。同時(shí)成功地進(jìn)行了二氫卟吩e4的增量化合成實(shí)驗(yàn)。以萃取時(shí)間為40min，萃取物與萃取劑用量比為1：40，萃取次數(shù)為3次對合成產(chǎn)物進(jìn)行萃取，%。3. 針對國內(nèi)外尚無明確報(bào)道的二氫卟吩e4及UF的光敏性及光漂白特性進(jìn)行了分析討論。研究了6個(gè)不同濃度條件下，二氫卟吩e4的光譜特性和光漂白特性：二氫卟吩e4在不同濃度的溶液中以單體形式存在；二氫卟吩e4的光漂白特性為光學(xué)修飾型，二氫卟吩e4的漂白半衰期大于80min，在腫瘤治療過程中，有利于光進(jìn)入更深層次，增加了治療深度，有利于PDT治療。分別對UF粉末及UF液體的穩(wěn)定性進(jìn)行了實(shí)驗(yàn)研究。結(jié)果表明，在低溫（0℃—4℃）、避光條件下UF粉末的貯存期限應(yīng)在在210天內(nèi)；在低溫（0℃—4℃）、避光條件下UF液體的貯存期限應(yīng)在30天內(nèi)。研究了6個(gè)不同濃度的UF在進(jìn)行不同時(shí)間的垂直照射光照后的吸收光譜的變化。通過吸收光譜變化對UF的光漂白特性進(jìn)行了評價(jià)，UF的光漂白屬于光學(xué)修飾型 ，UF的漂白半衰期遠(yuǎn)大于90min，因而有利于PDT治療。關(guān)鍵詞：二氫卟吩e6；二氫卟吩e4；UF； HPLC； 光譜；光敏性；光漂白SYNTHESIS AND PHOTOSENSITIVENESS OF NOVEL CHLORIN PHOTOSENSITIZERSMajor: Materials Physics and Chemistry Name: Jun WangSupervisor: Professor Yifan LuoABSTRACTThis paper discussed the novel antitumor drug—chlorin e6, chlorin e4 and UF (UF is an advanced posite photosensitizer which is synthetised by chlorin e6 , chlorin e4 and other pounds)photosensitizer which is based on silkworm excrement proper to our country as material. Some new experiment results are obtained and illustrated as following:1. Study on PLATISIL ODS 5μm (250mm) column in chlorin e6 and chlorin e4 is carry out high performance liquid chromatography(HPLC) detection. Optimum analysis conditions of chlorin e6 providing the best resolution of analytes was performed by gradient elution with mobile phases of mol?L1 ammonium acetate solution and methanol. Reversedphase conditions: 85%（%/min）→100% 。 flow rate: mL?min1。 detection wavelength: 407nm. The peak area of chlorin e6 and concentration achieved good linear relation ranged from to , r=, the stability(RSD)was %, the precision (RSD) was %.Optimum analysis conditions of chlorin e4 providing the best resolution of analytes was performed by gradient elution with mobile phases of mol?L1 ammonium acetate solution and methanol. Reversedphase conditions: 85%（%/min）→100% 。 flow rate: mL?min1。 detection wavelength: 400nm. The peak area of chlorin e6 and concentration achieved good linear relation ranged from to , r=, the stability(RSD)was %, the precision (RSD) was %.2. According to the best synthesis condition of chlorin e6: reaction system to be isolated from oxygen and nitrogen access, at 140℃ returning 25min, we succeed in incremental synthesis and refining of chlorin e6. And have made the product’s purity upgrade to 80%. Screen out optimum extraction method: extraction time 40min, the ratio of extractive and extraction agent is 1:40。 study out a innoxious method of synthesis chlorin e6: removal of the toxic reagents pyridine and acetone, replaced the noxious methyl alcohol with innoxious reagents alcohol. After extraction the product of new synthesis method could surpass 80%.Orthogonal test to optimize the best method of synthesis of chlorin e4 is used. Optimum synthesis condition is 160℃, 20min. At the same time, succeed in incremental synthesis and refining of chlorin e4. Take the extraction time as 40min, the ratio of extractive and extraction agent is 1:40, leaching for 3 times. This improved the purity crude chlorin e4 product to %.3. To the question that leck of analysis of spectrum properties and the photobleaching of chlorin e4 and UF both in abroad and at home, we discussed these properties the properties and the photobleaching of chlorin e4 under 6 different concentrations. The experimental result show that chlorin e4 is present as monomers in different concentration and its photobleaching is photology modified. The photobleaching experimental of chlorin e4 also show that the half lifetime of photosensitizer chlorin e4 is much longer than 80min, this enhanced both of the treat deepness of cancer and the effects of treatment of PDT.Does key research to the stability analysis of powder UF and liquid UF. The experimental result indicates that the guaranteed period for powder UF is 210 days keep in dark plce and low temperature(0℃—4℃)。 the guaranteed period for liquid UF is 30 days keep in dark plce and low temperature(0℃—4℃).Study the photosensitiveness and the photobleaching of UF under 6 different concentrations. Evaluating the photobleaching of UF by absorptionspectra. The experimental result show that UF is present as monomers in different concentrations. The photobleaching experimental of UF also show that the half lifetime of photosensitizer UF is much longer than 90min, and this enhanced the effects of treatment of PDT.KEY WORDS: Chlorin e6。 Chlorin e4。 UF。 HPLC。 Spectrum。 Photosensitiveness。 Photobleaching 75目 錄摘 要 I目 錄 I第一章 緒 論 1 選題依據(jù)及研究內(nèi)容 1 光動力療法簡介 3 光動力療法的作用要素 3 光動力療法的臨床特點(diǎn) 4 光動力療法的作用機(jī)制 5 光動力療法的歷史 7 光動力療法的應(yīng)用現(xiàn)狀 8 光動力治療存在的問題和前景展望 8 二氫卟吩類光敏劑的合成與研究進(jìn)展 9 二氫卟吩e6 9 二氫卟吩e4 10 mTHPC 10 MACE（Npe6） 11 光敏劑的光學(xué)特性 11 光敏劑的光譜特性 11 光敏劑的光漂白特性 12參考文獻(xiàn)： 13第二章 二氫卟吩e6的增量合成 17 實(shí)驗(yàn)部分 17