肉桂油微乳体系的构建及其肠吸收研究

发布时间：2018-06-21 20:40

  本文选题：肉桂油微乳 + 稳定性考察　； 参考：《南昌大学》2014年硕士论文

【摘要】：本文构建了一种安全性高、载油量适中的肉桂油微乳体系，测定其理化参数，考察其稳定性，并研究其体外释放和肠吸收情况，主要研究内容及结果如下： 1.肉桂油微乳体系的构建 以转相乳化法制备微乳。通过电导率法精确控制水相的加入，并以离心法作为微乳的初步判断方法，以离心结果和伪三元相图中微乳区域面积大小，作为微乳稳定性的初步判断依据，对肉桂油微乳体系构建的原料和工艺参数进行初步筛选，最终优化微乳体系组成为：Tween80/EL-40/丙三醇/无水乙醇/IPM/肉桂油/水，其中Tween80：EL-40=3：1，丙三醇：无水乙醇=1：1，肉桂油：IPM=1：1，Km=4，制备温度为40℃，水相为64.29%。所制备微乳为O/W型微乳，淡黄色，澄清透明；平均粒径为14.6nm，pH、电导率、折光率、粘度分别为5.03、228μs/cm、1.3829、46.5mpa·s，肉桂醛含量为21.27mg/mL。 2.肉桂油微乳体系稳定性考察 参考本实验室建立的高效液相色谱法检测肉桂醛，以加热-冷却循环试验、高速离心试验和恒温加速试验考察肉桂油微乳稳定性。结果显示：在20μg/mL～160μg/mL范围内，峰面积与肉桂醛浓度有良好的线性关系，标准曲线方程为：y=162.7x+169，决定系数R2=0.998。加热冷却循环试验和高速离心试验中，肉桂油微乳体系均未出现相分离；恒温加速试验中除pH值变化较大外，其他参数变化较小，恒温加速六个月后，肉桂醛含量保留率依然维持在90%以上，而相同条件下的肉桂油中肉桂醛含量保留率仅为46.52%，表明本实验构建的微乳体系稳定性良好，，且能有效减少肉桂醛的损失。 3.肉桂油微乳体系的体外释放 以正向透析扩散法分别考察肉桂油微乳体系在人工胃液、pH6.8和pH7.4人工肠液中的释放情况，并对释放情况进行拟合。结果显示：人工胃液中，肉桂醛遭到破坏，所选五种方程均无法较好的描述其释放情况，但从实验结果看，由于实际应用中肉桂油微乳体系在胃中停留时间一般不超过1.5h，因此并不影响肉桂醛等物质的释放或者影响很小；人工肠液中pH值不同，释放情况有所不同，但肉桂油微乳的释放情况均符合Retger-peppas方程。其中pH6.8人工肠液中释放方程为：Q=8.6642t0.6118，R2=0.9980；pH7.4人工肠液中释放方程为：Q=3.9064t0.7904，R2=0.9719。 4.肉桂油微乳体系肠吸收 以外翻肠囊法考察肉桂油微乳体系离体肠吸收情况，并比较肉桂油微乳体系与普通乳液小肠吸收情况，结果表明：①肉桂醛在小肠的吸收速度为空肠十二指肠回肠，且空肠肠段的吸收明显大于十二指肠和回肠；②离体实验中肉桂醛累积吸收量并不随时间延长而呈现一直增长的趋势，但本实验条件下，相同时间内，肉桂油微乳体系累积吸收百分数均高于肉桂油普通乳液。 以单向肠灌流实验考察肉桂油微乳体系在体肠吸收情况，考察恒流泵流速和剂型对小肠吸收的影响，结果表明：①在设定的恒流泵流速（204μL/min、301μL/min）下，恒流泵流速越大，小肠肉桂醛阶段吸收量和累积吸收量越大；②本实验条件下，小肠对肉桂醛的累积吸收量与吸收时间呈良好的线性关系，R20.99；③相同条件下，肉桂油微乳体系中肉桂醛阶段吸收量普遍高于肉桂油普通乳液；肉桂油微乳体系中肉桂醛累积吸收量和累积吸收百分数均高于肉桂油普通乳液。表明肉桂油微乳体系小肠吸收要优于肉桂油普通乳液，生物利用度可能更高。
[Abstract]:In this paper, a high safety, oil loaded cinnamon oil microemulsion system was constructed, its physical and chemical parameters were measured, its stability was investigated, and its in vitro release and intestinal absorption were studied. The main contents and results were as follows:
Construction of 1. cinnamon oil microemulsion system
The microemulsion was prepared by the method of phase transfer emulsification. The water phase was accurately controlled by the conductivity method, and the centrifugal method was used as the preliminary judgment method of microemulsion. The size of the microemulsion area in the centrifuge result and the pseudo three element phase diagram was used as the preliminary judgement basis for the stability of microemulsion. The raw materials and technological parameters of the microemulsion system of cinnamon oil were preliminarily screened. The final optimization microemulsion system consists of Tween80/EL-40/ glycerol / anhydrous ethanol /IPM/ cinnamon oil / water, of which Tween80:EL-40=3:1, glycerol: anhydrous ethanol =1:1, cinnamon oil: IPM=1:1, Km=4, the preparation temperature is 40 C, the microemulsion prepared by the water phase is O/W microemulsion, yellowish yellow, clear and transparent; the average particle size is 14.6nm, pH, The conductivity, refractive index and viscosity were 5.03228 s/cm, 1.3829,46.5mpa? S and cinnamaldehyde 21.27mg/mL. respectively.
Study on the stability of 2. cinnamon oil microemulsion system
The performance of cinnamaldehyde was examined by high performance liquid chromatography (HPLC) established in our laboratory. The stability of cinnamon oil microemulsion was investigated by heating cooling cycle test, high speed centrifugation test and constant temperature accelerated test. The results showed that there was a good linear relationship between the peak area and the concentration of cinnamaldehyde in the range of 20 to 160 g/mL, and the standard curve equation was y=162.7x+169 The determination coefficient R2=0.998. heating cooling cycle test and high speed centrifugation test, cinnamon oil microemulsion system has no phase separation; in the constant temperature acceleration test, the change of pH value is relatively large, the other parameters are small, and after six months of constant temperature acceleration, the retention rate of cinnamaldehyde is still more than 90%, and cinnamon oil in cinnamon oil under the same condition The retention rate of aldehyde content is only 46.52%, indicating that the microemulsion system constructed in this experiment has good stability and can effectively reduce the loss of cinnamaldehyde.
In vitro release of 3. cinnamon oil microemulsion system
The release of cinnamon oil microemulsion system in artificial gastric juice, pH6.8 and pH7.4 artificial intestinal fluid was investigated by positive dialysis diffusion method, and the release conditions were fitted. The results showed that cinnamaldehyde was destroyed in the artificial gastric juice, and the five equations were not good to describe the release situation, but from the experimental results, the actual application was used. The retention time of cinnamon oil microemulsion system generally does not exceed 1.5h in the stomach, so it does not affect the release or effect of Cinnamaldehyde and other substances. The release of pH in the artificial intestinal fluid is different, but the release of cinnamon oil microemulsion is in accordance with the Retger-peppas equation. The release equation in the pH6.8 artificial intestinal fluid is: Q=8.6642t0 The release equation of.6118, R2=0.9980 and pH7.4 artificial intestinal juice is: Q=3.9064t0.7904, R2=0.9719.
Intestinal absorption of 4. cinnamon oil microemulsion system
The absorption of cinnamon oil microemulsion system in vitro, and the absorption of cinnamon oil microemulsion system and common emulsion small intestine were compared. The results showed that: (1) the absorption rate of cinnamaldehyde in the small intestine was the jejunum duodenum, and the absorption of the jejunum intestine was greater than that of the twelve finger intestine and ileum; The cumulative absorption did not increase with time, but in the same time, the cumulative absorption percentage of cinnamon oil microemulsion system was higher than that of cinnamon oil in the same time.
The absorption of cinnamon oil microemulsion system in the intestines was investigated by one way intestinal perfusion test. The effect of the flow rate and dosage form on the absorption of small intestine was investigated. The results showed that the greater the flow velocity of constant current pump (204 L/min, 301 L/min), the greater the absorption and cumulative absorption of cinnamaldehyde in the small intestine; Under the same condition, the absorption of cinnamaldehyde in cinnamaldehyde oil microemulsion system is generally higher than that of cinnamaldehyde oil in the same condition. The cumulative absorption and cumulative absorption percentage of cinnamaldehyde in cinnamon oil microemulsion system are higher than that of cinnamon oil in the same condition. The absorption of cinnamon oil microemulsion in the small intestine is better than that in cinnamon oil emulsion, and the bioavailability may be higher.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R96


本文编号：2049937