论文总字数：17195字

摘 要

奥曲肽是种八肽环化合物。有生长抑制素的功能，无法在自然界直接获得。它在体内的衰退时间为1.5-2小时，并且有很强的抑制激素分泌的能力。醋酸奥曲肽是奥曲肽的醋酸盐，是一种白色的粉末状固体。它与奥曲肽有同样的性质。奥曲肽常用于治疗激素分泌失常所引发的疾病。醋酸奥曲肽目前上市的有两种剂型，一种是注射液Sandostatin®，另一种是储库式注射用微球Sandostatin LAR® Depot，两种剂型虽然没有明显的药效学差异。但是注射用缓释微球可以减少患者的用药量。因此可防止耐药性的产生，降低药物的毒性副作用。所以，研发微球剂型的科研任务刻不容缓。

本课题采用复乳化溶剂挥发法制备醋酸奥曲肽缓释微球。主要是因为这种方法制备的微球对药物的包覆率高，制剂均匀，药物释放稳定。

本课题通过实验初步建立醋酸奥曲肽微球的制备方法，并对制备出的微球进行工艺参数考察。待确立微球的制备方法后，通过小试阶段工艺考察的结果，选出载药量最高和突释现象出现概率较低的微球制备方法。

关键字：醋酸奥曲肽 微球 复乳溶剂挥发法

ABSTRACT

Octreotide is a octapeptide ring compound.It has the function of somatostatin, can not be obtained directly in nature. The recession time of octreotide is 1.5-2 hours in the body, and has a strong ability to inhibit hormone secretion. Octreotide acetate is a white powdery solid. It has the same properties as octreotide. Octreotide is commonly used to treat diseases caused by hormone disorders. Acetyl Acetate is currently available in two formulations.One is Sandostatin^® and another is Sandostatin LAR^® Depot, although there is no difference significant pharmacodynamic between the two formulations. However, slow-release microspheres for injection can reduce the dosage of the patient. So that the production of drug resistance can be prevented and the toxic side effects of the drug can be reduced. Therefore, the research and development of microsphere formulations of scientific research tasks without delay.

In this paper, octreotide acetate microspheres were prepared by multiple emulsion solvent evaporation. Mainly because of this method of preparation of microspheres on the drug coverage rate was high, uniform preparation, drug release stability.

In this research, the preparation method of octreotide acetate microspheres was established by the experiment, and the process parameters of the prepared microspheres were investigated. After the preparation method of microspheres was established, the preparation method of microspheres with the highest probability of drug loading and the probability of burst release was selected by the results of small test.

Keywords: octreotide acetate microspheres multiple emulsion solvent evaporation

目录

摘要 I

ABSTRACT II

第一章 文献综述 1

1.1醋酸奥曲肽概述 1

1.1.1奥曲肽及其醋酸衍生物的性质 1

1.1.2醋酸奥曲肽的上市剂型 1

1.2微球剂型概述 2

1.2.1微球剂型简介及科研状况 2

1.2.2微球的制备工艺 3

1.3载体材料聚乳酸-羟基乙酸（PLGA）介绍 4

1.3.1聚乳酸-羟基乙酸（PLGA）简介 4

1.3.2聚乳酸-羟基乙酸（PLGA）优点 4

1.4论文研究内容 5

第二章 醋酸奥曲肽缓释微球的制备方法的建立及微球工艺的考察 6

2.1试验材料 6

2.2试验仪器 6

2.3微球制备 7

2.3.1内水相溶液的配制 7

2.3.2中油相溶液的配制 7

2.3.3外水相溶液的配制 7

2.3.4磷酸缓冲液的配制 7

2.3.5初乳的制备 7

2.3.6复乳的制备，微球的洗涤和收集 8

2.3.7冻干 9

2.3.8分装保存 10

2.4微球工艺的考察 10

2.4.1醋酸奥曲肽微球形态 10

2.4.2载药量的测定 10

2.4.3制备参数考察 11

2.4.4体外释放实验测定微球突释现象 11

第三章 实验结果与分析 12

3.1微球形态 12

3.2色谱实验 12

3.2.1色谱条件 12

3.2.2线性关系考察 12

3.2.3含量检测结果 15

3.3 PLGA浓度的影响 16

3.4醋酸奥曲肽浓度的影响 17

3.5复乳搅拌速度的影响 18

3.6表面活性剂PVA浓度的影响 19

3.7初乳乳化强度的影响 20

3.8体外释放实验结果 21

3.9结果与讨论 22

第四章 总结与展望 23

参考文献 24

致谢 27

文献综述

1.1 醋酸奥曲肽概述

1.1.1 奥曲肽及其醋酸衍生物的性质

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