CN105816428B - 一种雷公藤内酯醇纳米脂质体及其制备方法 - Google Patents

一种雷公藤内酯醇纳米脂质体及其制备方法 Download PDF

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CN105816428B
CN105816428B CN201610275859.2A CN201610275859A CN105816428B CN 105816428 B CN105816428 B CN 105816428B CN 201610275859 A CN201610275859 A CN 201610275859A CN 105816428 B CN105816428 B CN 105816428B
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triptolide
nano liposomes
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林绥
阙慧卿
钱丽萍
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FUJIAN ACADEMY OF MEDICAL SCIENCES
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Abstract

本发明属于雷公藤内酯醇制剂的制备领域，具体涉及一种雷公藤内酯醇纳米脂质体及其制备方法。按重量分数计，其原料组成为：卵磷脂0.1‑0.2%，硬脂酸0.02‑0.04%，poloxamer188 0.2%，甘油2.25%，雷公藤内酯醇0.008‑0.016%，余量为水。本发明通过采用高压均质法将雷公藤内酯醇制成纳米脂质体，平均包封率为88.52%，平均粒径为97.8nm，Zeta电位为31.7。

Description

一种雷公藤内酯醇纳米脂质体及其制备方法
技术领域
本发明属于雷公藤内酯醇制剂的制备领域，具体涉及一种雷公藤内酯醇纳米脂质体及其制备方法。
背景技术
雷公藤内酯醇（Triptolide，又称雷公藤内酯，雷公藤甲素）是一种免疫抑制剂，对移植器官的排斥反应有很强的抑制作用。大量体内和体外的研究证明，雷公藤内酯醇对多种癌症如白血病、乳腺癌、胰腺癌及肺癌等均有良好的抗肿瘤活性。然而目前适用的雷公藤内酯醇制剂由于其严重的毒副反应而限制了它的使用，脂质体作为药物载体具有能增加与细胞的亲和力，提高疗效，口服减轻对胃肠道刺激，降低副作用的特点。
“雷公藤内酯醇脂质体的制备，林建峰、苏志伟等，第四次全国雷公藤学术会议论文汇编，2004年05月”用反相蒸发法制备雷公藤内酯醇脂质体，雷公藤内酯醇脂质体形态轮廓清晰，呈圆球形囊状颗粒，平均粒径为255nm，包封率为86.18%。然而其不足之处在于：平均粒径为255nm，不是纳米级（小于100nm）的脂质体，而我们现在制备的是纳米级的脂质体，平均粒径为97.8nm，具有一定的靶向性。纳米脂质体（nano liposomes）是一种在常规脂质体的基础上结合纳米技术发展起来的新型载药系统，在稳定性、吸收和体内分布等方面具有纳米粒子的特殊效应，可以携载亲水性、疏水性及两亲性药物，直接输送至靶组织发挥药效作用。
泊洛沙姆(Poloxamer)为聚氧乙烯聚氧丙烯醚嵌段共聚物，商品名为普兰尼克(Pluronic)。这是一类新型的高分子非离子表面活性剂。Poloxamer188（Pluronic F68）作为一种水包油乳化剂是目前用于静脉乳剂极少数合成乳化剂之一。用量0.1%～5%。用本品制备的乳剂，乳粒少，一般在1μm以下，吸收率高。物理性质稳定，能够耐受热压灭菌和低温冰冻。
发明内容
本发明的目的在于针对现有技术的不足，提供一种雷公藤内酯醇纳米脂质体及其制备方法。本发明通过采用高压均质法将雷公藤内酯醇制成纳米脂质体，平均包封率为88.52%，平均粒径为97.8nm，Zeta电位为31.7。
为实现本发明的目的，采用如下技术方案：
一种雷公藤内酯醇纳米脂质体，按重量分数计，其原料组成为：卵磷脂0.1-0.2%，硬脂酸0.02-0.04%，poloxamer188 0.2%，甘油2.25%，雷公藤内酯醇0.008-0.016%，余量为水。
一种如上所述的雷公藤内酯醇纳米脂质体的制备方法，采用高压均质法制得纳米脂质体；包括以下步骤：
1）将卵磷脂、硬脂酸置于同一圆底烧杯中，加入适量二氯甲烷溶解，再加入雷公藤内酯醇溶解充分后，置旋转蒸发挥尽二氯甲烷，并在烧瓶壁上形成一层薄膜；
2）将poloxamer188溶于80 ℃ 300 ml等温等渗的甘油水溶液中，作为水相；
3）待水相冷却至35-45℃，将水相加入步骤1）的圆底烧杯中，使薄膜脱落并充分溶解；
4）将溶解均匀的溶液于高压均质机中，在85MPa均质10min。
本发明与现有技术比较具有以下优点：
本发明通过采用高压均质法将雷公藤内酯醇制成纳米脂质体，平均包封率为88.52%，平均粒径为97.8nm，Zeta电位为31.7；制备方法简单，易于操作。
具体实施方式
为进一步公开而不是限制本发明，以下结合实例对本发明作进一步的详细说明。
实施例1
一种雷公藤内酯醇纳米脂质体，按重量分数计，其原料组成为：卵磷脂0.1%，硬脂酸0.04%，poloxamer188 0.2%，甘油2.25%，雷公藤内酯醇0.012%，余量为水。
一种如上所述的雷公藤内酯醇纳米脂质体的制备方法，采用高压均质法制得纳米脂质体；包括以下步骤：
1）将卵磷脂、硬脂酸置于同一圆底烧杯中，加入适量二氯甲烷溶解，再加入雷公藤内酯醇溶解充分后，置旋转蒸发挥尽二氯甲烷，并在烧瓶壁上形成一层薄膜；
2）将poloxamer188溶于80 ℃ 300 ml等温等渗的甘油水溶液中，作为水相；
3）待水相冷却至40℃，将水相加入步骤1）的圆底烧杯中，使薄膜脱落并充分溶解；
4）将溶解均匀的溶液于高压均质机中，在85MPa均质10min。
实施例2
一种雷公藤内酯醇纳米脂质体，按重量分数计，其原料组成为：卵磷脂0.2%，硬脂酸0.03%，poloxamer188 0.2%，甘油2.25%，雷公藤内酯醇0.016%，余量为水。
一种如上所述的雷公藤内酯醇纳米脂质体的制备方法，采用高压均质法制得纳米脂质体；包括以下步骤：
1）将卵磷脂、硬脂酸置于同一圆底烧杯中，加入适量二氯甲烷溶解，再加入雷公藤内酯醇溶解充分后，置旋转蒸发挥尽二氯甲烷，并在烧瓶壁上形成一层薄膜；
2）将poloxamer188溶于80 ℃ 300 ml等温等渗的甘油水溶液中，作为水相；
3）待水相冷却至35℃，将水相加入步骤1）的圆底烧杯中，使薄膜脱落并充分溶解；
4）将溶解均匀的溶液于高压均质机中，在85MPa均质10min。
实施例3
一种雷公藤内酯醇纳米脂质体，按重量分数计，其原料组成为：卵磷脂0.15%，硬脂酸0.02%，poloxamer188 0.2%，甘油2.25%，雷公藤内酯醇0.008%，余量为水。
一种如上所述的雷公藤内酯醇纳米脂质体的制备方法，采用高压均质法制得纳米脂质体；包括以下步骤：
1）将卵磷脂、硬脂酸置于同一圆底烧杯中，加入适量二氯甲烷溶解，再加入雷公藤内酯醇溶解充分后，置旋转蒸发挥尽二氯甲烷，并在烧瓶壁上形成一层薄膜；
2）将poloxamer188溶于80 ℃ 300 ml等温等渗的甘油水溶液中，作为水相；
3）待水相冷却至45℃，将水相加入步骤1）的圆底烧杯中，使薄膜脱落并充分溶解；
4）将溶解均匀的溶液于高压均质机中，在85MPa均质10min。
以上所述仅为本发明的较佳实施例，凡依本发明申请专利范围所做的均等变化与修饰，皆应属本发明的涵盖范围。

Claims (1)

1.一种雷公藤内酯醇纳米脂质体，其特征在于：按重量分数计，其原料组成为：卵磷脂0.1-0.2%，硬脂酸0.02-0.04%，poloxamer188 0.2%，甘油2.25%，雷公藤内酯醇0.008-0.016%，余量为水；其制备方法为采用高压均质法制得纳米脂质体；包括以下步骤：
1）将卵磷脂、硬脂酸置于同一圆底烧杯中，加入适量二氯甲烷溶解，再加入雷公藤内酯醇溶解充分后，置旋转蒸发挥尽二氯甲烷，并在烧瓶壁上形成一层薄膜；
2）将poloxamer188溶于80 ℃ 300 ml等温等渗的甘油水溶液中，作为水相；
3）待水相冷却至35-45℃，将水相加入步骤1）的圆底烧杯中，使薄膜脱落并充分溶解；
4）将溶解均匀的溶液于高压均质机中，在85MPa均质10min。
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CN114831962A (zh) * 2022-04-29 2022-08-02 福建省医学科学研究院 一种雷公藤内酯醇固体脂质纳米粒及其滴丸的制备方法

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