魔芋膠基胃漂浮控釋系統(tǒng)的構(gòu)建與調(diào)控
發(fā)布時間：2019-05-13 19:40
【摘要】：營養(yǎng)與藥物的遞送系統(tǒng)研究,是這些生理活性物質(zhì)研究的延續(xù),因其通常能夠有效提高藥物或營養(yǎng)素在體內(nèi)的生物利用率,并降低毒副作用,近年來正成為國際研究熱點(diǎn)和產(chǎn)業(yè)競爭的焦點(diǎn)。胃漂浮控釋系統(tǒng)的密度小于胃液,因此能夠漂浮而不受到胃排空的影響,從而有利于那些需要在胃部釋放的藥物及營養(yǎng)素的定位。該技術(shù)的核心競爭在于高親水、可漂浮的高分子輔料的創(chuàng)新及其基礎(chǔ)上系統(tǒng)的構(gòu)建。 本研究的目的是盡量采用簡便安全低成本方式,將魔芋膠這種天然親水膠制備成一種既可漂浮又有控釋性能的材料,并將其作為賦形劑應(yīng)用到胃漂浮控釋系統(tǒng)中,以評價其效果。從而探討將魔芋膠應(yīng)用推進(jìn)到藥輔領(lǐng)域之可能,以應(yīng)對魔芋價格的日漸高漲。 主要研究結(jié)果如下： 1.球磨法調(diào)控魔芋膠的粉體與膠體特性。選擇球磨處理的方式,對其進(jìn)行粒徑分布、粉體流動性、比表面積、松密度、輕敲密度、吸濕性、分子量、結(jié)晶性質(zhì)、表面形態(tài)、流變特性進(jìn)行表征。結(jié)果發(fā)現(xiàn)球磨處理后,魔芋膠d50從152μm逐漸降低到20μm；粉體休止角和比表面積變大；松密度與輕敲密度均降低；球磨4h、d5o為45.3μm的魔芋膠壓縮性最好：空氣濕度60%以下利于魔芋膠的貯藏；8h的球磨處理能使魔芋膠分子量從9.52×105g/mol降低到4.65×105g/mol;魔芋膠結(jié)晶性質(zhì)并不受球磨處理的影響；球磨處理使魔芋膠顆粒表面變得粗糙,當(dāng)粒徑低至20μm時,有團(tuán)聚現(xiàn)象發(fā)生；球磨處理魔芋膠零切粘度減小,其流變模型遵循Cross方程。 2.魔芋膠基胃漂浮控釋系統(tǒng)構(gòu)建與評估。以甲硝唑?yàn)槟Ｐ退幬?考察魔芋膠含量、殼材厚度以及魔芋膠粒度對漂浮性能、釋藥性能的影響。結(jié)果表明魔芋膠能夠降低藥物釋放速率,藥片上下的阻釋層進(jìn)一步控制藥物釋放速率。賦形劑魔芋膠的粒度對釋放性能和漂浮性能有較大影響,以4h球磨的魔芋膠為賦形劑的藥片起漂最快,并且其釋藥曲線為零級控釋,有效地降低了突釋現(xiàn)象。利用核磁共振成像技術(shù)對溶出過程中藥片中的水分分布情況做了測試,結(jié)果表明以球磨處理4h的魔芋膠為賦形劑的藥片在與模擬胃液接觸的過程中更好地形成了凝膠屏障,比原樣藥片更有效地阻止水分的滲透從而達(dá)到了更好的釋放曲線。 3.魔芋膠基胃漂浮控釋系統(tǒng)優(yōu)化與調(diào)控。對4h球磨處理的魔芋膠進(jìn)行脫乙酰處理,并用不同脫乙酰度的魔芋膠與黃原膠共混,將其應(yīng)用到胃漂浮片中,以維生素B2為模型營養(yǎng)素。結(jié)果表明K1XO-DaO組可以在該載藥量下以零級方程對營養(yǎng)素進(jìn)行48h的持續(xù)釋放,預(yù)示普通維生素B2片每天服用3次的頻次被降為兩天服用1次。此外脫乙酰度和魔芋膠／黃原膠的共混比例對營養(yǎng)素的釋放率有雙向的調(diào)控作用,預(yù)示該系統(tǒng)可以根據(jù)藥物或營養(yǎng)素的要求,在較短或極長的時間內(nèi)進(jìn)行控制釋放。
[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.
【學(xué)位授予單位】：華中農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R94
本文編號：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.
【學(xué)位授予單位】：華中農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R94
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