魔芋胶基胃漂浮控释系统的构建与调控
发布时间：2019-05-13 19:40
【摘要】：营养与药物的递送系统研究,是这些生理活性物质研究的延续,因其通常能够有效提高药物或营养素在体内的生物利用率,并降低毒副作用,近年来正成为国际研究热点和产业竞争的焦点。胃漂浮控释系统的密度小于胃液,因此能够漂浮而不受到胃排空的影响,从而有利于那些需要在胃部释放的药物及营养素的定位。该技术的核心竞争在于高亲水、可漂浮的高分子辅料的创新及其基础上系统的构建。 本研究的目的是尽量采用简便安全低成本方式,将魔芋胶这种天然亲水胶制备成一种既可漂浮又有控释性能的材料,并将其作为赋形剂应用到胃漂浮控释系统中,以评价其效果。从而探讨将魔芋胶应用推进到药辅领域之可能,以应对魔芋价格的日渐高涨。 主要研究结果如下： 1.球磨法调控魔芋胶的粉体与胶体特性。选择球磨处理的方式,对其进行粒径分布、粉体流动性、比表面积、松密度、轻敲密度、吸湿性、分子量、结晶性质、表面形态、流变特性进行表征。结果发现球磨处理后,魔芋胶d50从152μm逐渐降低到20μm；粉体休止角和比表面积变大；松密度与轻敲密度均降低；球磨4h、d5o为45.3μm的魔芋胶压缩性最好：空气湿度60%以下利于魔芋胶的贮藏；8h的球磨处理能使魔芋胶分子量从9.52×105g/mol降低到4.65×105g/mol;魔芋胶结晶性质并不受球磨处理的影响；球磨处理使魔芋胶颗粒表面变得粗糙,当粒径低至20μm时,有团聚现象发生；球磨处理魔芋胶零切粘度减小,其流变模型遵循Cross方程。 2.魔芋胶基胃漂浮控释系统构建与评估。以甲硝唑为模型药物,考察魔芋胶含量、壳材厚度以及魔芋胶粒度对漂浮性能、释药性能的影响。结果表明魔芋胶能够降低药物释放速率,药片上下的阻释层进一步控制药物释放速率。赋形剂魔芋胶的粒度对释放性能和漂浮性能有较大影响,以4h球磨的魔芋胶为赋形剂的药片起漂最快,并且其释药曲线为零级控释,有效地降低了突释现象。利用核磁共振成像技术对溶出过程中药片中的水分分布情况做了测试,结果表明以球磨处理4h的魔芋胶为赋形剂的药片在与模拟胃液接触的过程中更好地形成了凝胶屏障,比原样药片更有效地阻止水分的渗透从而达到了更好的释放曲线。 3.魔芋胶基胃漂浮控释系统优化与调控。对4h球磨处理的魔芋胶进行脱乙酰处理,并用不同脱乙酰度的魔芋胶与黄原胶共混,将其应用到胃漂浮片中,以维生素B2为模型营养素。结果表明K1XO-DaO组可以在该载药量下以零级方程对营养素进行48h的持续释放,预示普通维生素B2片每天服用3次的频次被降为两天服用1次。此外脱乙酰度和魔芋胶／黄原胶的共混比例对营养素的释放率有双向的调控作用,预示该系统可以根据药物或营养素的要求,在较短或极长的时间内进行控制释放。
[Abstract]:The study of nutrition and drug delivery systems is a continuation of the study of these physiological active substances, which can usually effectively improve the bioavailability of drugs or nutrients in the body and reduce toxic and side effects. In recent years, it is becoming the focus of international research and industrial competition. The density of gastric floating controlled release system is less than that of gastric juice, so it can float without being affected by gastric emptying, which is beneficial to the localization of drugs and nutrients that need to be released in the stomach. The core competition of this technology lies in the innovation of high hydrophilic and floatable polymer excipients and the construction of the system on the basis of the technology. The purpose of this study is to prepare Konjac gum, a natural hydrophilic adhesive, into a material with both floating and controlled release properties in a simple, safe and low cost way, and to apply it as an excipient to the gastric floating controlled release system. To evaluate its effect. In order to deal with the rising price of Konjac gum, the possibility of promoting the application of konjac gum to the field of medicine was discussed. The main results are as follows: 1. The powder and colloid properties of konjac gum were regulated by ball milling. The particle size distribution, powder flowability, specific surface area, loose density, tap density, hygroscopicity, molecular weight, crystallization property, surface morphology and Rheological properties were characterized by ball milling. The results showed that after ball milling, the d _ (50) of konjac gum decreased from 152 渭 m to 20 渭 m, the rest angle and specific surface area of the powder increased, and the loose density and tapping density decreased. When ball milling for 4 hours, the compressibility of konjac gum with d5o of 45.3 渭 m was the best: the air humidity below 60% was beneficial to the storage of konjac gum. The molecular weight of konjac gum decreased from 9.52 脳 105g/mol to 4.65 脳 105 g 路mol after 8 h ball milling, and the crystallization properties of konjac gum were not affected by ball milling. The surface of Konjac gum particles became rough by ball milling treatment, and agglomeration occurred when the particle size was as low as 20 渭 m, and the zero shear viscosity of konjac gum treated by ball milling decreased, and the rheological model followed Cross equation. 2. Construction and evaluation of gastric floating controlled release system based on konjac gum. Using metronidazole as model drug, the effects of Konjac gum content, shell thickness and konjac gum particle size on floating properties and drug release properties were investigated. The results showed that Konjac gum could reduce the drug release rate, and the drug release rate was further controlled by the blocking layer above and below the tablets. The particle size of excipients Konjac gum has great influence on the release and floating properties. The tablets with 4 h ball milling Konjac gum as excipient float the fastest, and the release curve is zero order controlled release, which effectively reduces the sudden release phenomenon. The water distribution in the tablets during dissolution was tested by nuclear magnetic resonance imaging (NMR). The results showed that the tablets treated with konjac gum as excipient for 4 hours formed a better gel barrier in the process of contact with simulated gastric juice. It is more effective than the original tablets to prevent the infiltration of water and achieve a better release curve. 3. Optimization and regulation of gastric floating controlled release system based on konjac gum. The konjac gum treated by ball milling for 4 hours was deacetylated and mixed with xanthan gum with different deacetylation degree. It was applied to gastric floating tablets with vitamin B2 as model nutrient. The results showed that K1XO-DaO group could continuously release nutrients for 48 hours with zero order equation, indicating that the frequency of taking ordinary vitamin B2 tablets three times a day was reduced to once a day. In addition, the degree of deacetylation and the blending ratio of konjac gum / xanthan gum can regulate the release rate of nutrients in both directions, which indicates that the system can control the release in a short or very long time according to the requirements of drugs or nutrients.
【学位授予单位】：华中农业大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R94
本文编号：2476137
[Abstract]:The study of nutrition and drug delivery systems is a continuation of the study of these physiological active substances, which can usually effectively improve the bioavailability of drugs or nutrients in the body and reduce toxic and side effects. In recent years, it is becoming the focus of international research and industrial competition. The density of gastric floating controlled release system is less than that of gastric juice, so it can float without being affected by gastric emptying, which is beneficial to the localization of drugs and nutrients that need to be released in the stomach. The core competition of this technology lies in the innovation of high hydrophilic and floatable polymer excipients and the construction of the system on the basis of the technology. The purpose of this study is to prepare Konjac gum, a natural hydrophilic adhesive, into a material with both floating and controlled release properties in a simple, safe and low cost way, and to apply it as an excipient to the gastric floating controlled release system. To evaluate its effect. In order to deal with the rising price of Konjac gum, the possibility of promoting the application of konjac gum to the field of medicine was discussed. The main results are as follows: 1. The powder and colloid properties of konjac gum were regulated by ball milling. The particle size distribution, powder flowability, specific surface area, loose density, tap density, hygroscopicity, molecular weight, crystallization property, surface morphology and Rheological properties were characterized by ball milling. The results showed that after ball milling, the d _ (50) of konjac gum decreased from 152 渭 m to 20 渭 m, the rest angle and specific surface area of the powder increased, and the loose density and tapping density decreased. When ball milling for 4 hours, the compressibility of konjac gum with d5o of 45.3 渭 m was the best: the air humidity below 60% was beneficial to the storage of konjac gum. The molecular weight of konjac gum decreased from 9.52 脳 105g/mol to 4.65 脳 105 g 路mol after 8 h ball milling, and the crystallization properties of konjac gum were not affected by ball milling. The surface of Konjac gum particles became rough by ball milling treatment, and agglomeration occurred when the particle size was as low as 20 渭 m, and the zero shear viscosity of konjac gum treated by ball milling decreased, and the rheological model followed Cross equation. 2. Construction and evaluation of gastric floating controlled release system based on konjac gum. Using metronidazole as model drug, the effects of Konjac gum content, shell thickness and konjac gum particle size on floating properties and drug release properties were investigated. The results showed that Konjac gum could reduce the drug release rate, and the drug release rate was further controlled by the blocking layer above and below the tablets. The particle size of excipients Konjac gum has great influence on the release and floating properties. The tablets with 4 h ball milling Konjac gum as excipient float the fastest, and the release curve is zero order controlled release, which effectively reduces the sudden release phenomenon. The water distribution in the tablets during dissolution was tested by nuclear magnetic resonance imaging (NMR). The results showed that the tablets treated with konjac gum as excipient for 4 hours formed a better gel barrier in the process of contact with simulated gastric juice. It is more effective than the original tablets to prevent the infiltration of water and achieve a better release curve. 3. Optimization and regulation of gastric floating controlled release system based on konjac gum. The konjac gum treated by ball milling for 4 hours was deacetylated and mixed with xanthan gum with different deacetylation degree. It was applied to gastric floating tablets with vitamin B2 as model nutrient. The results showed that K1XO-DaO group could continuously release nutrients for 48 hours with zero order equation, indicating that the frequency of taking ordinary vitamin B2 tablets three times a day was reduced to once a day. In addition, the degree of deacetylation and the blending ratio of konjac gum / xanthan gum can regulate the release rate of nutrients in both directions, which indicates that the system can control the release in a short or very long time according to the requirements of drugs or nutrients.
【学位授予单位】：华中农业大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R94
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