發(fā)布時(shí)間：2018-06-17 02:15

  本文選題：SPG膜乳化 + PLGA　； 參考：《廣東藥學(xué)院》2014年碩士論文

【摘要】：本研究主要以PLGA為微球骨架材料，利用較新型的乳化方式—SPG膜乳化法，分別制備了一種脂溶性藥物微球即尼莫地平微球，和一種蛋白微球即溶菌酶微球。對(duì)制得這兩類(lèi)藥物微球進(jìn)行載藥量及體外緩釋效果評(píng)價(jià)，并對(duì)微球的其他性質(zhì)做了初步的評(píng)價(jià)。 在用O/W法制備尼莫地平微球時(shí)，首先以微球的外觀、載藥量及釋放行為為指標(biāo)研究了處方中各個(gè)因素對(duì)尼莫地平微球性質(zhì)的影響，通過(guò)單因素考察確定了制備尼莫地平微球的處方條件。之后對(duì)尼莫地平微球的工藝穩(wěn)定性、緩釋效果進(jìn)行了考察，最后對(duì)微球進(jìn)行表征。工藝單因素考察結(jié)果表明材料的黏度、材料用量對(duì)尼莫地平微球的包封率有較大影響，同時(shí)也影響著尼莫地平的體外釋放。還有SPG膜孔控制著微球的粒徑，對(duì)尼莫地平體外釋放也有一些影響。經(jīng)單因素考察優(yōu)化后的工藝所制備出尼莫地平微球的載藥量為16.33%，包封率為97.98%，粒徑是45.180μm，徑距1.523。其體外釋放與原料藥相比展示出很好的緩釋性能，連續(xù)40天釋放出55%，符合Ritger-peppas動(dòng)力學(xué)緩釋方程。DSC結(jié)果表明尼莫地平是以無(wú)定形的形式被包裹在微球材料中。 同時(shí)本研究采用W/O/W乳化法制備了溶菌酶PLGA微球，同樣對(duì)制備過(guò)程的處方因素進(jìn)行考察。結(jié)果顯示處方因素與尼莫地平微球相同，材料黏度與用量對(duì)微球的包封率有較大影響，此外由于是復(fù)乳法制備微球，其中內(nèi)水相的體積與添加劑也對(duì)蛋白微球制備有較大影響。在單因素考察中可制得載藥量為11.84%、包封率為72.43%的溶菌酶微球，平均粒徑為63.89μm。但其體外釋放一周僅釋放40%左右，之后釋放量極少，表現(xiàn)為不完全釋放。對(duì)溶菌酶微球的DSC表征及紅外表征顯示，溶菌酶被包裹在微球內(nèi)部；溶血試驗(yàn)顯示配制的溶菌酶微球混懸液無(wú)溶血現(xiàn)象；對(duì)其體內(nèi)外降解顯示體外降解7周基本無(wú)球形，，而組織切片顯示6周內(nèi)體內(nèi)微球在逐漸降解，且有良好的組織相容性。 本研究主要研究利用SPG膜乳化法制備了脂溶性化藥微球和蛋白類(lèi)微球，并對(duì)做出的微球的體內(nèi)、外的性質(zhì)進(jìn)行了初步評(píng)價(jià)，為之后利用SPG膜乳化法制備微球提供了相應(yīng)的參考。
[Abstract]:In this study, a kind of liposoluble drug microspheres, nimodipine microspheres, and a protein microsphere, lysozyme microspheres, were prepared by a new emulsification method-SPG membrane emulsification method using PLGA as the microsphere skeleton material. The drug loading and in vitro slow-release effect of the two kinds of microspheres were evaluated, and the other properties of the microspheres were also preliminarily evaluated. In the preparation of Nimodipine microspheres by O / W method, the effects of various factors on the properties of nimodipine microspheres were studied based on the appearance, drug loading and release behavior of the microspheres. The preparation conditions of nimodipine microspheres were determined by single factor investigation. Then the process stability and slow release effect of nimodipine microspheres were investigated. Finally, the microspheres were characterized. The results of single-factor investigation showed that the viscosity and the amount of the material had great influence on the encapsulation efficiency of nimodipine microspheres and also affected the release of nimodipine in vitro. The SPG pore also controls the particle size of the microspheres and has some effects on the release of nimodipine in vitro. Nimodipine microspheres were prepared by single factor investigation. The drug loading of Nimodipine microspheres was 16.33, the encapsulation efficiency was 97.98, the diameter was 45.180 渭 m and the diameter distance was 1.523. The in vitro release of Nimodipine showed a good sustained release performance compared with that of the bulk drug. It was released 55 times for 40 days. The results of DSC showed that Nimodipine was encapsulated in the microspheres in an amorphous form according to the Ritger-peppas kinetic slow-release equation .DSC results showed that Nimodipine was encapsulated in the microspheres in an amorphous form. At the same time, the lysozyme PLGA microspheres were prepared by W / O / W emulsification method. The results showed that the prescription factor was the same as that of nimodipine microspheres, and the viscosity and dosage of the materials had a great influence on the encapsulation efficiency of the microspheres. In addition, the volume of the inner water phase and the additive also had a great influence on the preparation of protein microspheres because of the preparation of the microspheres by the composite emulsion method. The lysozyme microspheres with an entrapment efficiency of 72.43% and an average particle size of 63.89 渭 m were prepared by single factor investigation. However, only about 40% of them were released in a week after release in vitro, but only a few of them were released in vitro, showing incomplete release. DSC and IR analysis of lysozyme microspheres showed that lysozyme was encapsulated in the microspheres, hemolysis test showed that there was no hemolysis in the suspension of lysozyme microspheres, and in vitro and in vivo degradation showed that there was basically no sphere in vitro. Tissue sections showed that the microspheres degraded gradually within 6 weeks and had good histocompatibility. In this study, lipid soluble drug microspheres and protein microspheres were prepared by SPG membrane emulsification method. The properties of the microspheres in vivo and in vitro were preliminarily evaluated, which provided a reference for the preparation of microspheres by SPG membrane emulsification method.
【學(xué)位授予單位】：廣東藥學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R943

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本文編號(hào)：2029154