【摘要】：聚乳酸(Polylactic acid,PLA)具有良好的生物可降解性、生物相容性以及良好的力學性能和加工性能,是生物降解醫(yī)用材料領域中最受重視的材料之一,在緩釋藥物體系中具有重要的應用價值。但是,聚乳酸表面的疏水性基團使其的親水性較低,導致細胞相容性降低,不利于藥物被細胞吸收從而降低了藥效。為了改善聚乳酸的性能缺陷,提高其親水性和降解性能,增加聚乳酸在緩釋藥物體系中的使用性能,本文對聚乳酸進行了改性,并以改性聚乳酸為囊材制備了聚乳酸載藥微球,研究了聚乳酸載藥微球的釋藥性能。(1)采用五氯化磷(PCl5)為酰氯化試劑聚乳酸進行酰氯化反應,然后與己二胺反應從而制備得到己二胺改性的聚乳酸(EPLA)。隨后對產(chǎn)物的結(jié)構(gòu)進行了傅里葉紅外光譜以及核磁共振氫譜的測試表征,從而證明了己二胺被接枝到聚乳酸上。(2)使用上一步制備的己二胺改性聚乳酸(EPLA)為原料,先與戊二醛反應再與膠原蛋白反應得到膠原蛋白改性聚乳酸。通過傅里葉紅外以及異硫氰酸熒光素標記熒光光譜測試對改性后的聚乳酸進行了表征,結(jié)果表明戊二醛以及膠原蛋白被成功的接枝到到己二胺改性的聚乳酸上。并且通測得改性的聚乳酸中,膠原蛋白的接枝率為8.7%。(3)對材料進行了性能測定。測試表明:膠原蛋白、戊二醛與己二胺共同改性作用下的聚乳酸的親水性最好,己二胺改性聚乳酸次之,而PLA的親水性相對最差。從材料的失重率以及降解介質(zhì)的pH變化方面,考察材料的降解性能。測定結(jié)果表明:降解的初期,改性聚乳酸的失重率高于聚乳酸,PLA在之后降解過程中的失重率始終高于EPLA、CPLA。在降解過程中,未改性聚乳酸的降解介質(zhì)的pH發(fā)生明顯的下降,而EPLA和CPLA的降解介質(zhì)的pH也出現(xiàn)了下降的現(xiàn)象,但是其下降幅度較小。(4)以膠原蛋白改性聚乳酸為囊材,胰蛋白酶為芯材,采用水包油包水(W1/O/W2)型溶劑揮發(fā)法制備得到載胰蛋白酶改性聚乳酸微球。研究得到了載藥微球的最佳工藝條件:水油相比為1:6,CPLA與胰蛋白酶的質(zhì)量比為1:6,初乳的攪拌速率為14000 r/min,聚乙烯醇濃度為0.75%,復乳的攪拌速率為800 r/min,聚乳酸的濃度為5.0%。利用環(huán)境掃描電鏡對制備的載藥微球的形貌進行表征,結(jié)果表明載藥微球的成球效果比較好,表面比較光滑且形貌圓整,分散性良好,微球大小比較均勻。在最佳工藝條件下制備的載藥微球的平均粒徑為:PLA載藥微球為2.75μm,EPLA載藥微球為4.22μm,CPLA載藥微球為4.09μm。研究測定了三種載藥微球的包封率和載藥量,結(jié)果為CPLA(29)EPLA(29)PLA。研究測定了胰蛋白酶載藥微球的體外釋藥性能,結(jié)果表明:與PLA載藥微球相比,EPLA載藥微球和CPLA載藥微球具有更好的長效緩釋效果。
[Abstract]:Polylactic acid (Polylactic) has good biodegradability, biocompatibility, good mechanical properties and processability. It is one of the most important materials in the field of biodegradable medical materials, and has important application value in slow-release drug system. However, the hydrophobic group on the surface of polylactic acid makes its hydrophilicity lower, leading to the decrease of the cell compatibility, which is not conducive to the absorption of the drug by the cell and thus reduces its efficacy. In order to improve the performance defects of polylactic acid, improve its hydrophilicity and degradation performance, and increase the performance of polylactic acid in slow-release drug system, the polylactic acid microspheres were prepared with modified PLA as capsule material in this paper. The release properties of poly (lactic acid) loaded microspheres were studied. (1) Polylactic acid (EPLA).) modified by hexanediamine was prepared by acylation of poly (lactic acid) with phosphorous pentachloride (PCl5) as acylated reagent and then reaction with hexanediamine. The structure of the product was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). It was proved that hexane diamine was grafted onto polylactic acid. (2) Hexanediamine modified polylactic acid (EPLA) was used as raw material. Collagen modified polylactic acid was obtained by first reacting with glutaraldehyde and then with collagen. The modified poly (lactic acid) was characterized by FTIR and fluorescein isothiocyanate labeling. The results showed that glutaraldehyde and collagen were successfully grafted onto the polylactic acid modified by hexanediamine. The graft rate of collagen in modified PLA was 8.7%. (3) the properties of the modified PLA were determined. The results showed that the hydrophilicity of poly (lactic acid) modified by collagen glutaraldehyde and hexanediamine was the best and that of hexanediamine was the second while the hydrophilicity of PLA was the worst. The degradation performance of the material was investigated from the aspects of the weight loss rate and pH change of the degradation medium. The results showed that in the early stage of degradation, the weight loss rate of modified PLA was higher than that of PLA after degradation. In the process of degradation, the pH of the degradation medium of unmodified polylactic acid decreased obviously, while the pH of the degradation medium of EPLA and CPLA also decreased, but the decrease was relatively small. (4) the collagen modified polylactic acid was used as the capsule material. Polylactic acid microspheres modified by trypsin were prepared by water in oil in water (W1/O/W2) solvent volatilization method with trypsin as core material. The optimum technological conditions were obtained as follows: the mass ratio of water-oil ratio 1: 6 CPLA to trypsin was 1: 6, the mixing rate of colostrum was 14000 r / min, the concentration of polyvinyl alcohol was 0.75%, the mixing rate of composite emulsion was 800 r / min, and the concentration of polylactic acid was 5.0%. The morphology of the drug-loaded microspheres was characterized by environmental scanning electron microscope. The results showed that the drug-loaded microspheres had a good effect of forming, the surface was smooth, the morphology was round, the dispersity was good, and the size of the microspheres was uniform. The average particle size of the drug-loaded microspheres prepared under the optimum conditions was 2.75 渭 m EPLA-loaded microspheres, 4.22 渭 m CPLA microspheres and 4.09 渭 m CPLA microspheres. The encapsulation efficiency and drug loading capacity of three kinds of drug-loaded microspheres were determined. The results were as follows: CPLA (29) EPLA (29) PLA. The in vitro release properties of trypsin loaded microspheres were studied. The results showed that PLA microspheres and CPLA loaded microspheres had better long-term sustained release effects than those of PLA loaded microspheres.
【學位授予單位】：齊魯工業(yè)大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：O633.14;TQ460.1

【相似文獻】

相關期刊論文 前10條

1 韓敏;蘇秀霞;李仲謹;;載藥微球制劑的研究進展[J];應用化工;2007年05期

2 崔嘉揚;樂黃鶯;沈振陸;;基于樹枝狀嵌段共聚物的載藥微球的制備及其藥物釋放表征[J];上海交通大學學報(農(nóng)業(yè)科學版);2012年06期

3 李航;袁華;仲謙;任杰;;5-氟尿嘧啶載藥微球的制備工藝及性能研究[J];功能材料;2007年02期

4 章莉娟;錢宇;潘吉錚;;聚合物載藥微球活性組分控釋性能的動力學模擬[J];化工學報;2006年08期

5 李峻峰;張利;李鈞甫;鄒琴;楊維虎;李玉寶;;香草醛交聯(lián)殼聚糖載藥微球的性能及其成球機理分析[J];高等學校化學學報;2008年09期

6 張琳琳;涂姜磊;徐靜;程莉萍;張志斌;陳世龍;;殼聚糖-海藻酸鈉載藥微球的緩釋性能研究[J];材料導報;2010年24期

7 李春生,壽崇琦,左志俊;載藥微球釋放規(guī)律的實驗研究[J];化學研究與應用;1999年03期

8 張愛英,李杰,馮增國,張勇;生物可降解聚乙二醇-b-聚對苯二甲酸丁二醇酯共聚物載藥微球的制備[J];應用化學;2003年03期

9 尚紅梅;李引乾;曹新宇;陳輝玲;董玲玲;童德文;馬永梅;;SiO_2載藥微球的研究及應用[J];材料導報;2012年S1期

10 楊黎燕;李仲謹;尤靜;張靜姝;;淀粉基交聯(lián)共聚載藥微球的制備及其生物性能研究[J];應用化工;2011年10期

相關會議論文 前5條

1 王彥卿;張朝平;;磁性明膠載藥微球的制備及體外釋藥研究[A];第五屆中國功能材料及其應用學術會議論文集Ⅱ[C];2004年

2 馬桂蕾;宋存先;韓銳;付招娣;;帶有微孔結(jié)構(gòu)紫杉醇微球制備及其在小鼠體內(nèi)抗腫瘤活性研究[A];天津市生物醫(yī)學工程學會2006年學術年會論文摘要集[C];2006年

3 劉艷飛;黃可龍;彭東明;劉素琴;吳弘;;聚碳酸亞丙酯馬來酸酐酯的合成及其載藥微球的制備[A];第十屆中國科協(xié)年會論文集（三）[C];2008年

4 劉艷飛;黃可龍;彭東明;劉素琴;吳弘;;聚碳酸亞丙酯馬來酸酐酯的合成及其載藥微球的制備[A];第十屆中國科協(xié)年會第18分會二氧化碳減排和綠色化利用與發(fā)展研討會論文集[C];2008年

5 簡永增;王耀先;程樹軍;;聚酸酐載藥微球的制備[A];2005年全國高分子學術論文報告會論文摘要集[C];2005年

相關博士學位論文 前1條

1 李近;可生物降解載藥微球的制備和釋藥動力學的研究[D];清華大學;2008年

相關碩士學位論文 前10條

1 童欣;5-Fu/GoFe_2O_4/PCL磁性載藥微球的制備及其表征[D];大連海事大學;2015年

2 王敬龍;多層載藥微球型骨修復材料的制備及其對HPMSCs生物學活性影響的研究[D];吉林大學;2016年

3 陸海玲;磁性熒光聚合物載藥微球的制備及應用[D];廣東藥科大學;2016年

4 王秋艷;基于氧化海藻酸鈉載藥微球的制備與研究[D];華南理工大學;2016年

5 張竹;結(jié)腸靶向納米載藥微球的制備及其體外釋藥行為研究[D];重慶大學;2016年

6 崔苗苗;聚乳酸的改性及其在緩釋藥物體系中的應用研究[D];齊魯工業(yè)大學;2016年

7 吳海燕;絲素載藥微球的制備及其性能研究[D];蘇州大學;2008年

8 孫愛平;噴霧干燥法制備聚乳酸載藥微球及其藥物釋放行為研究[D];天津大學;2008年

9 趙天倚;聚乳酸包覆次血紅素六肽微球的制備及初步活性研究[D];吉林大學;2011年

10 康世胤;復合功能載藥微球的制備及在脊髓損傷治療中的應用初探[D];天津大學;2011年

，

本文編號：2198938