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原位聚合法制备缓释微囊

发布时间:2018-10-25 06:30
【摘要】:原位聚合法是一种制备微囊的新方法。它以芯材物质为分散相,把可溶性预聚体与酸性催化剂全部加入连续相中。首先,单体进行反应生成预聚体,加入酸性催化剂后预聚体开始聚合,当预聚体聚合尺寸逐步增大后,沉积在芯材物质的表面而成囊。预聚体在连续相中是可溶的,而其聚合物在整个体系中是不可溶的,聚合反应在分散相芯材上发生。 阿维菌素是一种以胃毒作用为主和兼有触杀作用的生物杀螨、杀虫、杀线虫剂,具有低毒、高效、无公害、与其他农药使用无交互抗性以及不易产生抗药性等特点,因此被广泛应用于害虫防治。但是,阿维菌素在使用过程中易受紫外线和微生物的影响而发生分解,影响药效的发挥。将阿维菌索微囊化可以减少阿维菌索在使用中的降解,延长其药效,减少资源浪费,降低用药成本。本文对原位聚合法反应过程中的处方和工艺进行了研究,并制备出符合要求的阿维菌索缓释微囊。 首先确定了高效液相色谱检测条件:色谱柱,大连依利特Hypersil (4.6mm×200mm,5μm);流动相,甲醇—水(90:10);流速,0.7mL/min;检测波长,245nm。建立了阿维菌素微囊的高效液相色谱检测方法,确定了药物含量的检测方法,确定了释放介质的组成及释放度的测定方法。 预聚体的制备实验中,经过对处方和工艺的单因素考察确定了大致的范围,分别以囊材的生成量和微囊的外观为评价指标,通过正交设计优化了了预聚体制备的处方和工艺,得到最优的条件为:脲醛分子比1:1.8,pH=8.5,在70℃水浴温度下缓慢搅拌反应75min。制备得到无色透明、性质稳定的粘稠预聚体溶液。 乳剂的制备实验中,首先对油相组成和乳化剂进行了筛选,确定溶解有阿维菌素的质量比为3:4的甲苯和氯苯的混合溶剂为油相,质量比为1:2的阿拉们胶和AE09为复合乳化剂。经过对乳剂制备处方和工艺的单因素考察确定了大致的范围。通过正交优化实验得到乳剂最优的制备条件为:油水质量比为13:100,乳化剂占油相质量的30%,剪切搅拌转速为4000rpm,搅拌时间为4min。制备得到粒径分布均匀,性质稳定的白色乳剂。 微囊的制备实验中,首先确定了乳剂和预聚体的质量比为1:3,考察了酸化过程中的工艺与处方参数,通过正交优化设计得到最佳的酸化工艺为:酸化pH=2.5,加酸速度3mL/min,搅拌速度600rpm,室温下酸化1.5h。并通过加入抗粘剂改善了微囊的粘连情况。对助悬剂的种类和用量进行了筛选,确定1.0%的黄原胶作为微囊混悬液的助悬剂。 最终得到了外观为均匀白色的微囊混悬液,经测定微囊粒径在1-12μm,跨距为1.604,药物含量2.0±0.1%,包封率98.6%以上。于阿维菌素乳剂相比有显著的缓释作用,释放度符合要求。
[Abstract]:In situ polymerization is a new method for preparing microcapsules. The soluble prepolymer and acid catalyst were added to the continuous phase with the core material as the dispersed phase. First, the monomer reacts to form the prepolymer, and the prepolymer begins to polymerize after adding the acid catalyst. When the size of the prepolymer increases gradually, the prepolymer is deposited on the surface of the core material to form a capsule. The prepolymer is soluble in the continuous phase, while the polymer is insoluble in the whole system, and the polymerization takes place on the core of the dispersed phase. Abamectin is a kind of biological mite killing, insecticidal and nematicidal agent, which is mainly caused by stomach toxicity and has contact effect. It has the characteristics of low toxicity, high efficiency, no pollution, no cross resistance with other pesticides, and is not easy to produce resistance to insecticides. Therefore, it is widely used in pest control. However, abamectin is easy to decompose under the influence of UV and microorganism, which affects the effect of Avermectin. Microencapsulation of avermectin can reduce the degradation of Avernoid in use, prolong its efficacy, reduce the waste of resources and reduce the cost of medication. In this paper, the formulation and process of in situ polymerization reaction were studied, and Avermectin sustained-release microcapsules were prepared. The detection conditions were determined as follows: column, 4.6mm 脳 200mm-1 5 渭 m); mobile phase, methanol-water (90:10), flow rate, 0.7 mL / min, detection wavelength, 245 nm. A high performance liquid chromatography (HPLC) method for the determination of abamectin microcapsules was established. In the preparation experiment of prepolymer, the formulation and process of prepolymer were optimized by orthogonal design, taking the quantity of capsule and the appearance of microcapsule as evaluation indexes. The optimum conditions are as follows: the molar ratio of urea-formaldehyde is 1: 1.8g, pH = 8.5, stirring slowly at 70 鈩,

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