本文關(guān)鍵詞：溫敏性脯氨酸系列多肽材料的制備與性能　出處：《河北大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 溫敏特性 氨基酸-N-羧基環(huán)內(nèi)酸酐(NCA) 多肽材料 生物相容性

【摘要】：溫敏性聚合物是指能夠?qū)ν饨鐪囟茸兓鞒隹赡骓憫?yīng)的一類智能材料。近年來,溫敏性聚合物已應(yīng)用于藥物釋放、生物分離、酶的固定等研究領(lǐng)域。溫敏性聚合物的重要參數(shù)是最低臨界溶液溫度(LCST)或最高臨界溶液溫度(UCST),而良好的生物可降解性和生物相容性則是其實(shí)際應(yīng)用的重要保證。在本文中,以幾種天然的氨基酸為原料,合成其相應(yīng)的氨基酸-N-羧基-環(huán)內(nèi)酸酐(NCA)單體,通過開環(huán)聚合反應(yīng),直接制備出沒有任何修飾并且兼具良好生物相容性和優(yōu)異溫敏特性的多肽生物材料。論文主要分四個(gè)部分:一、在文獻(xiàn)綜述部分,簡(jiǎn)單介紹了溫敏性聚合物研究現(xiàn)狀,主要包括多肽概述、分類及其實(shí)際應(yīng)用。二、以天然的L-脯氨酸和肌氨酸為原料,合成了L-脯氨酸-N-羧基環(huán)內(nèi)酸酐(LP-NCA)和肌氨酸-N-羧基環(huán)內(nèi)酸酐(SA-NCA)單體,經(jīng)開環(huán)共聚合制備出溫敏性聚(L-脯氨酸-co-肌氨酸)多肽生物材料(PPS)。通過FTIR、1H NMR、UV、XRD和CD等方法系統(tǒng)地表征單體與多肽生物材料的結(jié)構(gòu)與性能。不同于傳統(tǒng)的溫敏性聚合物,PPS水溶液在升溫與降溫過程中,顯示了復(fù)雜的相轉(zhuǎn)變行為,即PPS在水中具有最低臨界溶解溫度(LCST=37℃)和最高臨界溶解溫度(UCST=30℃)雙重特性。CD結(jié)果表明:在升溫和降溫過程中,多肽鏈上肌氨酸結(jié)構(gòu)單元的引入有效地改變了原有的二級(jí)結(jié)構(gòu),即PPS出現(xiàn)第一次相變后,隨著溫度繼續(xù)變化以及H鍵相互作用減弱或升高,PPS再次出現(xiàn)第二次相變。此外,在PPS溶液中HeLa細(xì)胞的存活率在24 h和48 h后仍達(dá)到70%左右,表明其優(yōu)異的生物相容性�？傊�,具有溫度響應(yīng)性和低細(xì)胞毒性的多肽生物材料PPS在生物醫(yī)學(xué)領(lǐng)域具有潛在的應(yīng)用價(jià)值。三、以天然的L-脯氨酸和L-丙氨酸為原料,利用L-脯氨酸-N-羧基環(huán)內(nèi)酸酐(LP-NCA)和L-丙氨酸-N-羧基環(huán)內(nèi)酸酐(LA-NCA)兩種單體開環(huán)共聚,成功的制備出溫敏性生物多肽材料,即聚(L-脯氨酸-co-L-丙氨酸)(PPA)。依據(jù)多肽PPA(脯氨酸結(jié)構(gòu)單元含量56%-78%)水溶液透光率與溫度變化曲線可知,升溫時(shí)其LCST為75℃,降溫時(shí)其LCST為42℃,顯示出很寬的滯后現(xiàn)象。CD結(jié)果表明,在不同溫度下,PPA溶液吸收沒有明顯的變化,可見,其二級(jí)結(jié)構(gòu)具有較強(qiáng)的熱穩(wěn)定性。此外,在PPA溶液經(jīng)過24 h和48 h培養(yǎng),HeLa細(xì)胞存活率仍達(dá)到90%以上,表明PPA無明顯的細(xì)胞毒性。綜上,溫度響應(yīng)性多肽生物材料PPA有望應(yīng)用于藥物釋放、生物分離等生物醫(yī)學(xué)領(lǐng)域。四、以L-苯丙氨酸和L-脯氨酸為原料,通過合環(huán)反應(yīng)制備出氨基酸-N-羧基環(huán)內(nèi)酸酐(NCA)單體,通過兩種NCA單體的開環(huán)共聚合,成功制備出既有溫敏特性又有良好生物相容性的多肽生物材料。實(shí)驗(yàn)表明,在L-苯丙氨酸-N-羧基環(huán)內(nèi)酸酐(LPh-NCA)與L-脯氨酸-N-羧基環(huán)內(nèi)酸酐(LP-NCA)單體投料比為1:4時(shí),所得聚(L-脯氨酸-co-L-苯丙氨酸)(PPPh)才具有溫敏特性,其升溫時(shí)最低臨界溶解溫度(LCST)為71℃,且存在明顯的滯后現(xiàn)象。同時(shí),在PPPh多肽水溶液經(jīng)過24 h、48 h和72 h培養(yǎng),HeLa細(xì)胞的存活率已超過100%,表明PPPh多肽材料具有非常優(yōu)異的生物相容性�？傊�,溫度響應(yīng)性多肽生物材料PPPh有望應(yīng)用于藥物釋放、生物分離等生物醫(yī)學(xué)領(lǐng)域。
[Abstract]:Temperature sensitive polymer is a kind of smart material can make reversible response to external temperature changes. In recent years, Wen Min has been applied to polymer drug release, biological separation, etc. in the research field of fixed enzyme. The important parameters of temperature sensitive polymer is lower critical solution temperature (LCST) or UCST (the highest critical solution temperature), and the biodegradability and excellent biocompatibility is the important guarantee for the practical application. In this paper, using several kinds of natural amino acids as raw materials, the synthesis of the corresponding amino acid carboxyl -N- - ring anhydride (NCA) monomer through ring opening polymerization and direct preparation of polypeptide biological material without any modification and good biocompatibility and excellent Wen Min characteristics. The paper is divided into four parts: first, in the part of literature review, a brief introduction of Wen Min polymer research, mainly including the overview and classification of polypeptide. The practical application. Two, with natural L- proline and sarcosine as raw materials, L- proline -N- carboxyl ring anhydride synthesis (LP-NCA) and sarcosine -N- carboxyl ring anhydride (SA-NCA) monomer by ring opening copolymerization prepared temperature sensitive poly (L- proline -co- sarcosine) polypeptide biological materials (PPS). Through FTIR, 1H NMR, UV, structure and properties of XRD and CD methods systematically represent material monomer and peptide biological. Temperature sensitive polymer which is different from the conventional PPS solution during heating and cooling process, shows the phase transition behavior of complex, i.e. PPS has the lowest critical temperature in water (LCST=37 C) and the highest critical solution temperature (UCST=30 C).CD results showed that the dual characteristics in the heating and cooling process, the polypeptide chain into sarcosine structural unit effectively changed the two level structure of the original PPS, which appeared for the first time after transformation, with the the temperature continues to change And the H bond interaction decreased or increased, PPS phase appears second times again. In addition, in PPS solution, the survival rate of HeLa cells in 24 h and 48 h is reached about 70%, showed its excellent biocompatibility. In short, with the temperature response of biological materials and PPS polypeptide with low cytotoxicity potential applications in biomedical field. In three, the natural L- proline and L- alanine as raw material, the use of L- -N- ring proline carboxyl anhydride (LP-NCA) and L- alanine -N- carboxyl ring anhydride (LA-NCA) two monomer ring opening polymerization prepared temperature sensitive peptide material, i.e. poly (L- proline alanine -co-L- (PPA)). On the basis of the peptide PPA (56%-78% proline content unit) water solution transmittance and temperature change curve, the LCST temperature is 75 DEG C, cooling the LCST 42 degrees, showing a wide hysteresis.CD results show that, At different temperatures, PPA visible absorption did not change obviously, and the secondary structure has good thermal stability. In addition, in the solution of PPA after 24 h and 48 h culture, HeLa cell survival rate was more than 90%, PPA showed no significant cytotoxicity. In conclusion, the temperature response of biological materials is expected to PPA polypeptide applied to the field of drug release, biological separation and other biomedical. Four, L- and L- with phenylalanine proline as raw material, through the loop reaction preparation of amino acid -N- carboxyl ring anhydride (NCA) monomer, two kinds of NCA through ring opening copolymerization, prepared both temperature sensitivity and the compatibility of good biological polypeptide biological materials. Experimental results show that the anhydride in L- phenylalanine -N- carboxyl ring (LPh-NCA) and L- -N- proline carboxyl anhydride ring (LP-NCA) monomer feed ratio is 1:4, the poly (L- -co-L- phenyl alanine proline (PPPh) with temperature) The temperature sensitive characteristic, when the lower critical solution temperature (LCST) of 71 DEG C, and there is an obvious lag phenomenon. At the same time, the PPPh peptide aqueous solution after 24 h, 48 h and 72 h medium, the survival rate of HeLa cells is more than 100%, showed that the PPPh polypeptide material with excellent biocompatibility. In short, temperature responsive polypeptide biological material PPPh is expected to be applied to the field of drug release, biological separation and biomedical.

【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O636;TB381

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