CN112137959A - 一种卵质虾青素柔性纳米脂质体及制备方法 - Google Patents

一种卵质虾青素柔性纳米脂质体及制备方法 Download PDF

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CN112137959A
CN112137959A CN202010991651.7A CN202010991651A CN112137959A CN 112137959 A CN112137959 A CN 112137959A CN 202010991651 A CN202010991651 A CN 202010991651A CN 112137959 A CN112137959 A CN 112137959A
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季家弘
焦建
刘智阳
林健
王立强
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Guizhou Shangtu Biotechnology Co ltd
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Abstract

本发明是一种卵质虾青素柔性纳米脂质体及制备方法,柔性纳米脂质体为包覆卵质虾青素的柔性纳米脂质体,卵质虾青素是雨生红球藻经过以鸡为代表的禽类的体内转化、富集,在其卵黄内,形成以卵磷脂、脂质等成分包裹虾青素的状态,经工艺处理,可形成胶束或脂质体,更有利于人体吸收、利用及稳定性的提高,卵质虾青素柔性纳米脂质体成分组成:磷脂类化合物、膜柔软剂、膜稳定剂、体系稳定剂、蛋黄油(含卵质虾青素)。

Description

一种卵质虾青素柔性纳米脂质体及制备方法
技术领域
本发明属于医药技术领域,特别是涉及一种卵质虾青素柔性纳米脂质体的制备处方及其制备工艺。
背景技术
虾青素是一种类胡萝卜素,具有很强的抗氧化活性,比β-胡萝卜素、玉米黄质和叶黄素的抗氧化效力高10倍,比维生素E的高100倍。虾青素能清除人体内的自由基,减弱ROS和NMP对于真皮层胶原蛋白的破坏,从而发挥出强大的抗氧化、抗皱作用;同时,虾青素具有治疗慢性炎症、心血管疾病、糖尿病、代谢综合症、神经退行性疾病和抗癌症等功效。
雨生红球藻中虾青素的积累量高达5%,是天然虾青素的最佳来源。利用仿生学原理,在鸡的饲料中加入破壁的雨生红球藻,其中含有的虾青素在鸡的体内吸收运转,在其胚胎即卵黄内,形成以卵磷脂、脂质等成分包裹虾青素的状态富集在蛋黄中,利用超临界CO2萃取法提取蛋黄中蛋黄油,从而得到表面覆盖卵磷脂、脂质等成分的虾青素成分即为卵质虾青素。蛋黄中的脂质是提取后蛋黄油的主要成分,含有卵磷脂和胆固醇等成分,仅需添加部分磷脂及辅助成分即可制备脂质体。
虾青素稳定性差,异味浓烈、虾青素及其酯分子极性低、水溶性差,肠道对其的吸收慢,利用率低。如何设计一款安全、稳定、高含量、易吸收的虾青素运载体系,是虾青素应用于食品、医药、化妆品领域的关键。柔性纳米脂质体是第二代脂质体,由磷脂和膜柔软剂组成,结构与生物膜相似,它是一种多功能的靶向药物载体,与传统脂质体相比具有高度变形性,有利于促进药物进入皮肤表皮层和真皮层,可将大部分的药物留在皮肤中,减少进入人体血液循环的药物量,在表皮和真皮形成缓释药物库模型,使药物在局部持久治疗,口服制剂中,可提高肠道吸收卵质虾青素的膜渗透性,促进跨膜运动。
发明内容
本发明的目的在于提供一种卵质虾青素柔性纳米脂质体,解决了虾青素稳定性差,生物利用率低的难题。
本发明的另一目的在于提供一种适合于工业化生产的卵质虾青素柔性纳米脂质体的制备方法。
为了达成上述目的,本发明的技术方案是:
一种卵质虾青素柔性纳米脂质体,含有以下重量百分比的原料:磷脂类化合物20%-30%、膜柔软剂2.0%-3.0%、膜稳定剂5.0%-8.0%、体系稳定剂2%-5%、蛋黄油(含卵质虾青素0.5-5%)10.0%-20.0%、其余量为水化溶液(0.001 mol/L的磷酸缓冲液)。
一种卵质虾青素柔性纳米脂质体的制备工艺,(1)称取定量的磷脂类化合物、膜柔软剂、膜稳定剂、体系稳定剂和蛋黄油(含卵质虾青素0.5%-5%)溶于有机溶剂中,该有机溶剂为甲醇与三氯甲烷(体积比4:1)的混合溶液;(2)加入水化溶液适量后加热至40-50 ℃,启动高压均质机均质,维持压力40-100MPa,转速5000-10000 r/min均质20-60 min;(3)再加入余量已预热至40-50℃的水化溶液,均质的同时减压(0.01-0.05MPa)回收有机溶剂,甲醇和三氯甲烷的限度分别为不得过3000ppm及60ppm,均质20-60 min,即得卵质虾青素柔性纳米脂质体。
其中,本发明所述磷脂类化合物为蛋黄卵磷脂、大豆卵磷脂、二棕榈酰胆碱、糖神经胺醇脂中的一种或几种;
所述膜柔软剂包括泊洛沙姆188(F68)、甘氨胆酸钠和聚二甲基硅氧烷、十八醇酯硫酸酯中的一种或几种;
所述膜稳定剂为氨基聚乙二醇磷脂、琥珀酸胆固醇单酯、胆固醇癸二酸单烯酯中的一种或几种;
所述体系稳定剂为山茶籽油、紫苏籽油、壳聚糖、特丁基对苯二酚、β-二酮和环氧大豆油中的一种或几种;
所述磷脂类化合物与膜柔软剂的比例为8:1-12:1 ;
所述磷酯类化合物与蛋黄油(含卵质虾青素0.5%-5%)的比例为1:1-3:1 ;
所述水化溶液为0.001 mol/L的磷酸缓冲液。
所述蛋黄油(含卵质虾青素0.5-5.0%)为雨生红球藻经过以鸡为代表的禽类的体内转化、富集,在其卵黄内,形成以卵磷脂、脂质等成分包裹虾青素的状态。
采用上述技术方案后,本发明涉及的卵质虾青素柔性纳米脂质体有以下有益效果:一是柔性纳米脂质体作为药物载体具有高效的渗透性、高度的柔韧性和亲水性,能改变药物理化性质,提高药物吸收速率,使药物持久作用于病变部位,利用柔性纳米脂质体技术对卵质虾青素进行药学修饰,增加卵质虾青素稳定性并促进跨膜传递,提高生物利用度,代谢后对人体无任何副作用,安全有效;二是蛋黄油作为一种安全有效、药食两用的物质,含有丰富的维生素A、D和卵磷脂等,这些物质对皮肤的再生和代谢有着重要作用,蛋黄卵磷脂是血细胞和细胞膜所必须的原料,可以补充乙酰胆碱, 活化和再生脑细胞, 恢复和改善大脑功能, 防治老年性痴呆;虾青素除了极强的抗氧化活性外,还具有抑制肿瘤发生和生长、抵御紫外线、代维生素A活性、增强免疫功能、改善视力、调解血液中的胆固醇含量、提高繁殖性能力等诸多生理功能,同时,因其鲜艳的色泽,能增强动物的营养价值和抗病能力,在食品、饲料添加剂和化妆品行业都有很大的应用空间;山茶籽油等体系稳定剂可增加脂质体的稳定性,由此制备的卵质虾青素柔性纳米脂质体可运用于食品、医药、化妆品等多个领域。
本发明制备工艺操作简单,柔性纳米脂质体粒径均匀,稳定性好,易于工业化生产。
依据本发明制备得到的卵质虾青素柔性纳米脂质体可添加至口服制剂、透皮制剂和化妆品中。
具体实施方式
为了进一步解释本发明的技术方案,下面通过具体实施例来对本发明进行详细阐述。
实施例1:
本实施例中,一种卵质虾青素柔性纳米脂质体,包括以下重量百分比的原料:蛋黄卵磷脂20%、聚二甲基硅氧烷2.0%、氨基聚乙二醇磷脂 5.0%、山茶籽油2%、蛋黄油(含卵质虾青素3.0%)10.0%、其余量为水化溶液(0.001 mol/L的磷酸缓冲液)。
制备方法如下:
(1)称取定量的磷脂类化合物、膜柔软剂、膜稳定剂、体系稳定剂和蛋黄油(含卵质虾青素3.0%)溶于有机溶剂中,该有机溶剂为甲醇与三氯甲烷(体积比4:1)的混合溶液;
(2)加入水化溶液适量后加热至50 ℃,启动高压均质机均质,维持压力40MPa,转速8000 r/min,均质20 min;
(3)再加入余量已预热至50℃的水化溶液,均质的同时减压(0.01MPa)回收有机溶剂,甲醇和三氯甲烷的限度分别为不得过3000ppm及60ppm,均质20 min,即得卵质虾青素柔性纳米脂质体。
实施例2:
本实施例中,一种卵质虾青素柔性纳米脂质体,包括以下重量百分比的原料:蛋黄卵磷脂10%、大豆卵磷脂10%、聚二甲基硅氧烷4.0%、氨基聚乙二醇磷脂 8.0%、山茶籽油3%、蛋黄油(含卵质虾青素3.0%)20.0%、其余量为水化溶液。
制备方法如下:
(1)称取定量的磷脂类化合物、膜柔软剂、膜稳定剂、体系稳定剂和蛋黄油(含卵质虾青素3.0%)溶于有机溶剂中,该有机溶剂为甲醇与三氯甲烷(体积比4:1)的混合溶液;
(2)加入水化溶液适量后加热至50 ℃,启动高压均质机均质,维持压力40MPa,转速8000 r/min,均质40 min;
(3)再加入余量已预热至50℃的水化溶液,均质的同时减压(0.01MPa)回收有机溶剂,甲醇和三氯甲烷的限度分别为不得过3000ppm及60ppm,均质40 min,即得卵质虾青素柔性纳米脂质体。
实施例3
本实施例中,一种卵质虾青素柔性纳米脂质体,包括以下重量百分比的原料:大豆卵磷脂10%、二棕榈酰胆碱15%、甘氨胆酸钠4.0%、氨基聚乙二醇磷脂 8.0%、山茶籽油5%、蛋黄油(含卵质虾青素3.0%)20.0%、其余量为水化溶液。
制备方法如下:
(1)称取定量的磷脂类化合物、膜柔软剂、膜稳定剂、体系稳定剂和蛋黄油(含卵质虾青素3.0%)溶于有机溶剂中,该有机溶剂为甲醇与三氯甲烷(体积比4:1)的混合溶液;
(2)加入水化溶液适量后加热至50 ℃,启动高压均质机均质,维持压力40MPa,转速8000 r/min,均质60 min;
(3)再加入余量已预热至50℃的水化溶液,均质的同时减压(0.01MPa)回收有机溶剂,甲醇和三氯甲烷的限度分别为不得过3000ppm及60ppm,均质60 min,即得卵质虾青素柔性纳米脂质体。
实施例4
本实施例中,一种卵质虾青素柔性纳米脂质体,包括以下重量百分比的原料:大豆卵磷脂5%、蛋黄卵磷脂10%、二棕榈酰胆碱15%、十八醇酯硫酸酯4.0%、氨基聚乙二醇磷脂 8.0%、β-二酮3%、特丁基对苯二酚2%、蛋黄油(含卵质虾青素3.0%)20.0%、其余量为水化溶液(0.001 mol/L的磷酸缓冲液)。
制备方法如下:
(1)称取定量的磷脂类化合物、膜柔软剂、膜稳定剂、体系稳定剂和蛋黄油(含卵质虾青素3.0%)溶于有机溶剂中,该有机溶剂为甲醇与三氯甲烷(体积比4:1)的混合溶液;
(2)加入水化溶液适量后加热至50 ℃,启动高压均质机均质,维持压力40MPa,转速8000 r/min,均质60 min;
(3)再加入余量已预热至50℃的水化溶液,均质的同时减压(0.01MPa)回收有机溶剂,甲醇和三氯甲烷的限度分别为不得过3000ppm及60ppm,均质60 min,即得卵质虾青素柔性纳米脂质体。
实施例5
本实施例中,一种卵质虾青素柔性纳米脂质体,包括以下重量百分比的原料:二棕榈酰胆碱10%、蛋黄卵磷脂5%、二棕榈酰胆碱15%、甘氨胆酸钠4.0%、琥珀酸胆固醇单酯 8.0%、壳聚糖5%、蛋黄油(含卵质虾青素3.0%)10.0%、其余量为水化溶液(0.001 mol/L的磷酸缓冲液)。
制备方法如下:
(1)称取定量的磷脂类化合物、膜柔软剂、膜稳定剂、体系稳定剂和蛋黄油(含卵质虾青素4.0%)溶于有机溶剂中,该有机溶剂为甲醇与三氯甲烷(体积比4:1)的混合溶液;
(2)加入水化溶液适量后加热至50 ℃,启动高压均质机均质,维持压力40MPa,转速8000 r/min,均质60 min;
(3)再加入余量已预热至50℃的水化溶液,均质的同时减压(0.01MPa)回收有机溶剂,甲醇和三氯甲烷的限度分别为不得过3000ppm及60ppm,均质60 min,即得卵质虾青素柔性纳米脂质体。

Claims (9)

1.一种卵质虾青素柔性纳米脂质体,其特征在于,含有以下重量百分比的原料: 磷脂类化合物20%-30%、膜柔软剂2.0%-3.0%、膜稳定剂5.0%-8.0%、体系稳定剂2%-5%、含卵质虾青素的蛋黄油10.0%-20.0%、其余量用0.001 mol/L的磷酸缓冲液作为水化溶液。
2.如权利要求1所述的一种卵质虾青素柔性纳米脂质体,其特征在于:磷脂类化合物与膜柔软剂的比例为8:1-12:1。
3.如权利要求1所述的一种卵质虾青素柔性纳米脂质体,其特征在于:磷酯类化合物与蛋黄油的比例为1:1-3:1。
4.如权利要求1或3所述的一种卵质虾青素柔性纳米脂质体,其特征在于:蛋黄油为含卵质虾青素0.5-5.0%的蛋黄油。
5.如权利要求1或2或3所述的一种卵质虾青素柔性纳米脂质体,其特征在于:磷脂类化合物可在蛋黄卵磷脂、大豆卵磷脂、二棕榈酰胆碱、糖神经胺醇脂中选取。
6.如权利要求1或2所述的一种卵质虾青素柔性纳米脂质体,其特征在于:膜柔软剂可在泊洛沙姆188(F68)、甘氨胆酸钠和聚二甲基硅氧烷、十八醇酯硫酸酯中选取。
7.如权利要求1所述的一种卵质虾青素柔性纳米脂质体,其特征在于:膜稳定剂可在氨基聚乙二醇磷脂、琥珀酸胆固醇单酯、胆固醇癸二酸单烯酯中选取。
8.如权利要求1所述的一种卵质虾青素柔性纳米脂质体,其特征在于:体系稳定剂可在山茶籽油、紫苏籽油、壳聚糖、特丁基对苯二酚、β-二酮和环氧大豆油中选取。
9.一种卵质虾青素柔性纳米脂质体的制备方法,其特征在于:
(1)称取定量的磷脂类化合物、膜柔软剂、膜稳定剂、体系稳定剂和蛋黄油(含卵质虾青素0.5%-5%)溶于有机溶剂中,该有机溶剂为甲醇与三氯甲烷(体积比4:1)的混合溶液;
(2)加入水化溶液适量后加热至40-50 ℃,启动高压均质机均质,维持压力40-100MPa,转速5000-10000 r/min均质20-60 min;
(3)再加入余量已预热至40-50℃的水化溶液,均质的同时减压(0.01-0.05MPa)回收有机溶剂,甲醇和三氯甲烷的限度分别为不得过3000ppm及60ppm,均质20-60 min,即得卵质虾青素柔性纳米脂质体。
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