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一种新型超油酸 20%w/w 静脉用脂肪乳剂及其在动物模型中对脂质和肝脏特征的影响。

A new alternative for intravenous lipid emulsion 20% w/w from superolein oil and its effect on lipid and liver profiles in an animal model.

机构信息

Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Parenteral Nutrition Unit, Department of Pharmacy, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.

出版信息

Daru. 2019 Jun;27(1):191-201. doi: 10.1007/s40199-019-00262-7. Epub 2019 Apr 24.

Abstract

PURPOSE

Intravenous lipid emulsion (IVLE) was first used to prevent essential fatty acids deficiency. IVLE with α-tocopherol was reported to provide protection against parenteral nutrition-associated liver disease. This study aims to determine the optimal parameters and conditions in developing a physically stable IVLE from superolein palm oil (SoLE 20%) and its effect on lipid and liver profiles in an animal model.

METHODS

SoLE 20% was prepared using superolein oil and MCT oil (1:1), stabilized with egg lecithin and homogenized using a high pressure homogenizer. Mean droplet size was used as the response variable and was measured using laser diffraction and dynamic light scattering method. Physical stability at 4 °C, 25 °C and 40 °C storage temperatures were determined based on particle size and distribution, polydispersity index, zeta potential, viscosity, vitamin E contents and pH. Sterility and pyrogenicity were also investigated. Rabbits were administered with 1.0 g/kg SoLE 20% for 5 h and repeated daily for 3 days to investigate its effect on blood lipid and liver enzymes profile.

RESULTS

SoLE 20% was succesfully prepared using the optimized parameters of 800 psi, 7 cycles and 1.2 g lecithin. The IVLE prepared had a particle size of 252.60 ± 4.88 nm and was physically stable for 4 weeks at different storage temperatures. SoLE 20% had a high content of natural vitamin E, remained sterile and pyrogen free. It was also safe for intravenous administration and did not alter the blood lipid (p > 0.05) and liver enzymes profiles (p > 0.05) of the rabbits.

CONCLUSION

The optimal parameters to develop a stable superolein based IVLE are 800 psi homogenization pressure, 7 homogenization cycles and using 1.2 g lecithin as the emulsifier. SoLE 20% is safe for intravenous administration and does not significantly alter lipid and liver enzymes profiles of the rabbits.

摘要

目的

静脉内脂肪乳剂(IVLE)最初用于预防必需脂肪酸缺乏症。含有α-生育酚的 IVLE 已被报道可预防肠外营养相关肝病。本研究旨在确定从超油棕榈油(SoLE20%)开发物理稳定的 IVLE 的最佳参数和条件,并在动物模型中研究其对脂质和肝脏谱的影响。

方法

使用超油和 MCT 油(1:1)制备 SoLE20%,用卵磷酯稳定并使用高压匀浆机匀化。平均粒径用作响应变量,使用激光衍射和动态光散射法测量。根据粒径和分布、多分散指数、Zeta 电位、粘度、生育酚含量和 pH 值,确定在 4°C、25°C 和 40°C 储存温度下的物理稳定性。还研究了无菌性和热原性。给兔子注射 1.0g/kg SoLE20%,每天 1 次,连续 3 天,以研究其对血脂和肝酶谱的影响。

结果

使用 800psi、7 个循环和 1.2g 卵磷酯的优化参数成功制备了 SoLE20%。制备的 IVLE 粒径为 252.60±4.88nm,在不同储存温度下 4 周内物理稳定。SoLE20%含有丰富的天然生育酚,无菌且无热原。它也可安全静脉注射,不会改变兔子的血脂(p>0.05)和肝酶谱(p>0.05)。

结论

开发稳定的基于超油的 IVLE 的最佳参数为 800psi 匀浆压力、7 次匀浆循环和使用 1.2g 卵磷酯作为乳化剂。SoLE20%静脉内给药安全,不会显著改变兔子的脂质和肝酶谱。

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