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CN110420180A - 一种含有维生素e的纳米乳药物及其制备方法 - Google Patents

一种含有维生素e的纳米乳药物及其制备方法 Download PDF

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CN110420180A
CN110420180A CN201910669573.6A CN201910669573A CN110420180A CN 110420180 A CN110420180 A CN 110420180A CN 201910669573 A CN201910669573 A CN 201910669573A CN 110420180 A CN110420180 A CN 110420180A
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欧阳五庆
兰莹
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Abstract

本发明公开了一种含有维生素E纳米乳药物，由维生素E 1g，依折麦布1g、吐温20 9 g、乙醇2 g和蒸馏水17 g组成。制备方法包括下列步骤：1）称取维生素E、依折麦布、表面活性剂、助表面活性剂和蒸馏水备用；2）将依折麦布加入维生素E中搅拌均匀，再加入助表面活性剂搅拌至完全溶解；3）将表面活性剂加入步骤2）制备的溶液中搅拌均匀；4）在室温下迅速搅拌步骤3）制备的溶液，搅拌的同时滴加蒸馏水，不断搅拌体系呈透明澄清的液体。本发明的纳米乳药物物疗效显著、安全方便、无毒副作用、且成本低廉。

Description

一种含有维生素E的纳米乳药物及其制备方法
技术领域
本发明属于医药技术领域，具体涉及一种含有维生素E纳米乳药物及其制备方法。
背景技术
随着现代社会的飞速发展，人们生活水平逐渐变好，宠物饮食也趋于高脂饮食，患上高血脂疾病的概率较高，另外宠物长期不运动，容易引起肥胖，肥胖的宠物大都血脂高，严重的可引发脉粥样硬化、冠心病、胰腺炎等疾病。患病宠物表现为精神沉郁，没有胃口食欲减退，懒惰不愿意活动等。因此可以通过降低血浆血脂水平，尤其是胆固醇的水平治疗高血脂。依折麦布( Ezetimibe) 是胆固醇吸收抑制剂，其主要通过减少肠道对胆固醇的吸收来降低饮食及胆汁中的胆固醇的水平，上述胆固醇约占总胆固醇的 75%。主要通过抑制小肠粘膜中一种特定的转运蛋白即 NPC1L1(niemann-pick c1 like1)来减少胆固醇的吸收，可同时降低血中及肝脏中贮存的胆固醇水平。维生素E可抑制体内胆固醇合成限速酶，即3-羟基-3甲基戊二酰辅酶A还原酶的活性，从而降低血浆胆固醇水平。
发明内容
针对上述现有技术中存在的问题与不足，本发明的目的在于提供一种含有维生素E纳米乳药物，该药物能够有效的降低血中及肝脏中贮存的胆固醇含量。
实现上述发明目的所采用的技术方案是：一种含有维生素E纳米乳药物，其特征在于，由维生素E 1g，依折麦布1g、吐温20 9 g、乙醇2 g和蒸馏水17 g组成。
本发明还一个目的是提供一种含有维生素E纳米乳药物的制备方法，具体包括下列步骤：
（1）称取维生素E，依折麦布、表面活性剂、助表面活性剂和蒸馏水备用；
（2）将依折麦布加入维生素E中搅拌均匀，再加入助表面活性剂搅拌至完全溶解；
（3）将表面活性剂加入步骤（2）制备的溶液中搅拌均匀；
（4）在室温下迅速搅拌步骤（3）制备的溶液，搅拌的同时滴加蒸馏水，不断搅拌体系呈透明澄清的液体。
与现有技术相比，本发明含有维生素E纳米乳药物具以下优点：
1）维生素E和依折麦布混合使用，有效的降低血中及肝脏中贮存的胆固醇含量。
2）本发明的纳米乳药物结构稳定，不会出现药物析出、分层等现象。
3）本发明的纳米乳药物疗效显著、安全方便、无毒副作用、且成本低廉。
附图说明
图1是本发明纳米乳药物的粒径图。
具体实施方式
实施例1
（1）取维生素E 1g，依折麦布1g、吐温20 9 g、乙醇2 g和蒸馏水17 g备用；
（2）将依折麦布加入维生素E中搅拌均匀，再加乙醇搅拌至完全溶解；
（3）将吐温20加入步骤（2）制备的溶液中搅拌均匀；
（4）在室温下迅速搅拌步骤（3）制备的溶液，搅拌的同时滴加蒸馏水，不断搅拌体系呈透明澄清的液体。
实验例1
1）粒径大小及形态学观察
用激光粒度测定仪测定维生素E纳米乳的粒径大小。通过透射电子显微镜观察其形态。2）稳定性考察
将维生素E纳米乳以13000r/min离心30min进行加速试验，分别在室温、4℃、和37℃条件下考察30d，每隔5d观察1次，置于日光下照射10d，于1、3、5、10d取样观察；分别观察以上试验中药物外观及粒径有无明显变化。
3）动物模型建立
选取活动自如的 6 周龄健康雄性 Wistar 大鼠，动物饲养环境隔音良好，室内温度适中（22±2）℃，湿度适宜 40%-50%，通风较好，采光良好，遵循动物正常活动规律，光照及黑暗交替，垫料洁净干燥，给予足量水及普通饲料喂养，使动物适应环境 1 周，完全高脂饲料喂养，并同时给予维生素 D3 经胃灌入（总量为 5×105 U/kg，3 天内灌入）。完全高脂饲料连续喂养 8 周，从高脂模型组中随机抽出2 只，将其麻醉处死，固定于鼠板，取出主动脉，清洗血液或血块，进行常规脱水，以石蜡块包埋并切片，对其进行HE染色，显微镜观察该段血管是否存在动脉粥样硬化及其严重程度，以确定高脂模型是否建立。从显微镜下观察到血管内膜增生和比较明显的脂质条纹突出时，可确定动脉粥样硬化动物模型造模成功。按照不同处理组的治疗方式治疗4周，于第12周进行血液生化指标检测。
4）分组和治疗
空白纳米乳组（A组）：按照维生素E纳米乳组灌胃大鼠纳米乳的体积灌胃空白纳米乳，1次/天；模型组（B组）：按照维生素E纳米乳组灌胃大鼠纳米乳的体积灌胃蒸馏水，1 次/天；依折麦布+维生素E组（C组）：按照大鼠剂量 5 mg/kg将溶于维生素E的依折麦布（比例同纳米乳中二者比例）灌胃，1 次/天.；维生素E纳米乳组（D组）：按照大鼠剂量5 mg/kg依折麦布将含有依折麦布的维生素E纳米乳灌胃，1 次/天。
5）血清指标的检测
分别于 8 周末眼静脉丛采血及 12 周末股动脉采血，测定 TC（总胆固醇）、TG（甘油三酯）、HDL-C（高密度脂蛋白胆固醇）、LDL-C（低密度脂蛋白胆固醇）水平。
6）结果
纳米乳平均粒径为28.76±12.68 nm。结果见图1。
稳定性结果表明高速离心后纳米乳仍呈澄清透明无沉淀，长时间室温放置及长时间日光照射纳米乳体系稳定。
大鼠 TG、TC、LDL-C、HDL-C 水平变化及组间比较，8 周末经检测发现，模型组大鼠与健康大鼠对比 TG、TC 及 LDL-C 水平均升高，HDL-C 水平降低，且存在统计学差异(P<0.05)，说明长期高脂饮食可造成大鼠血脂升高、HDL-C 降低，从另一个方面说明高脂模型塑造成功，下一阶段的实验研究可顺利进行。
12 周末时，大鼠血脂水平变化：（1）TG 水平比较：C、D组较 B 组 TG 水平明显降低（P<0.05），C、 D组与B组之间存在统计学差异（P<0.05），C组与D组之间存在统计学差异（P<0.05）。（2）TC 的比较：C、D组较 B 组 TC 水平明显降低（P<0.05）（3）LDL-C 水平比较：C、D组较 B 组LDL-C水平明显降低（P<0.05）。（4）C、D组较 B 组 HDL-C 水平明显升高（P<0.05），C、 D 组与 B组之间存在统计学差异（P<0.05），C组与 D 组之间无统计学差异（P>0.05）。（如表1所示）。
表 1 12 周末时大鼠血脂的结果（平均值±标准差）（单位 mmol/L）
组别 n TG TC HDL-C LDL-C
A 10 5.10±0.28 2.65±0.12 0.36±0.037 0.71±0.074
B 10 5.12±0.40 2.68±0.15 0.31±0.028 0.72±0.055
C 10 4.17±0.19#▲ 2.03±0.15#▲ 0.46±0.032#▲ 0.68±0.061#▲
D 10 3.29±0.11#*▲ 1.18±0.05#*▲ 0.92±0.029#*▲ 0.23±0.033#*▲
注：#各组与 B 组存在统计学差异，P<0.05；*各组与C组存在统计学差异，P<0.05。
▲各组与A组存在统计学差异，P<0.05。

Claims (2)

1.一种含有维生素E纳米乳药物，其特征在于，由维生素E 1g，依折麦布1g、吐温20 9g、乙醇2 g和蒸馏水17 g组成。
2.制备权利要求1所述含有维生素E纳米乳药物的制备方法，其特征在于，包括下列步骤：
（1）称取维生素E、依折麦布、表面活性剂、助表面活性剂和蒸馏水备用；
（2）将依折麦布加入维生素E中搅拌均匀，再加入助表面活性剂搅拌至完全溶解；
（3）将表面活性剂加入步骤（2）制备的溶液中搅拌均匀；
（4）在室温下迅速搅拌步骤（3）制备的溶液，搅拌的同时滴加蒸馏水，不断搅拌体系呈透明澄清的液体。
CN201910669573.6A 2019-07-24 2019-07-24 一种含有维生素e的纳米乳药物及其制备方法 Withdrawn CN110420180A (zh)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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CN101102768A (zh) * 2004-09-17 2008-01-09 中国医学科学院医药生物技术研究所 治疗高脂血症的方法和组合物
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Publication number Priority date Publication date Assignee Title
WO2005007111A2 (en) * 2003-07-11 2005-01-27 Bristol-Myers Squibb Company Tetrahydroquinoline derivatives as cannabinoid receptor modulators
CN101102768A (zh) * 2004-09-17 2008-01-09 中国医学科学院医药生物技术研究所 治疗高脂血症的方法和组合物
CN101679236A (zh) * 2007-01-24 2010-03-24 克尔克公司 依泽替米贝的制备方法和其的衍生物
US20130210794A1 (en) * 2010-06-18 2013-08-15 Genovéva Filipcsei Nanostructured ezetimibe compositions, process for the preparation thereof and pharmaceutical compositions containing them
CN103520103A (zh) * 2013-10-14 2014-01-22 陕西科技大学 一种维生素e纳米乳及其制备方法

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Application publication date: 20191108