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聚乳酸的改性及其在缓释药物体系中的应用研究

发布时间:2018-08-23 11:24
【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学性能和加工性能,是生物降解医用材料领域中最受重视的材料之一,在缓释药物体系中具有重要的应用价值。但是,聚乳酸表面的疏水性基团使其的亲水性较低,导致细胞相容性降低,不利于药物被细胞吸收从而降低了药效。为了改善聚乳酸的性能缺陷,提高其亲水性和降解性能,增加聚乳酸在缓释药物体系中的使用性能,本文对聚乳酸进行了改性,并以改性聚乳酸为囊材制备了聚乳酸载药微球,研究了聚乳酸载药微球的释药性能。(1)采用五氯化磷(PCl5)为酰氯化试剂聚乳酸进行酰氯化反应,然后与己二胺反应从而制备得到己二胺改性的聚乳酸(EPLA)。随后对产物的结构进行了傅里叶红外光谱以及核磁共振氢谱的测试表征,从而证明了己二胺被接枝到聚乳酸上。(2)使用上一步制备的己二胺改性聚乳酸(EPLA)为原料,先与戊二醛反应再与胶原蛋白反应得到胶原蛋白改性聚乳酸。通过傅里叶红外以及异硫氰酸荧光素标记荧光光谱测试对改性后的聚乳酸进行了表征,结果表明戊二醛以及胶原蛋白被成功的接枝到到己二胺改性的聚乳酸上。并且通测得改性的聚乳酸中,胶原蛋白的接枝率为8.7%。(3)对材料进行了性能测定。测试表明:胶原蛋白、戊二醛与己二胺共同改性作用下的聚乳酸的亲水性最好,己二胺改性聚乳酸次之,而PLA的亲水性相对最差。从材料的失重率以及降解介质的pH变化方面,考察材料的降解性能。测定结果表明:降解的初期,改性聚乳酸的失重率高于聚乳酸,PLA在之后降解过程中的失重率始终高于EPLA、CPLA。在降解过程中,未改性聚乳酸的降解介质的pH发生明显的下降,而EPLA和CPLA的降解介质的pH也出现了下降的现象,但是其下降幅度较小。(4)以胶原蛋白改性聚乳酸为囊材,胰蛋白酶为芯材,采用水包油包水(W1/O/W2)型溶剂挥发法制备得到载胰蛋白酶改性聚乳酸微球。研究得到了载药微球的最佳工艺条件:水油相比为1:6,CPLA与胰蛋白酶的质量比为1:6,初乳的搅拌速率为14000 r/min,聚乙烯醇浓度为0.75%,复乳的搅拌速率为800 r/min,聚乳酸的浓度为5.0%。利用环境扫描电镜对制备的载药微球的形貌进行表征,结果表明载药微球的成球效果比较好,表面比较光滑且形貌圆整,分散性良好,微球大小比较均匀。在最佳工艺条件下制备的载药微球的平均粒径为:PLA载药微球为2.75μm,EPLA载药微球为4.22μm,CPLA载药微球为4.09μm。研究测定了三种载药微球的包封率和载药量,结果为CPLA(29)EPLA(29)PLA。研究测定了胰蛋白酶载药微球的体外释药性能,结果表明:与PLA载药微球相比,EPLA载药微球和CPLA载药微球具有更好的长效缓释效果。
[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.
【学位授予单位】:齐鲁工业大学
【学位级别】:硕士
【学位授予年份】:2016
【分类号】:O633.14;TQ460.1

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