CN108619097A - 一种高效抗癌抗氧化复合脂质体 - Google Patents
一种高效抗癌抗氧化复合脂质体 Download PDFInfo
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Abstract
本发明属于保健食品及药品的技术领域，提供了一种高效抗癌抗氧化的复合脂质体及其制备方法。所述的复合脂质体主要由蛋黄卵磷脂、薏苡仁油、β‑胡萝卜素、胆固醇、磷酸氢二钠、磷酸二氢钠为原料组成。本发明所制备的复合脂质体具有较强的抗氧化活性及抗癌效果。相对于常规薏苡仁油脂质体、β‑胡萝卜素脂质体而言其抗氧化和抗癌活性显著提高。且该复合脂质体制备工艺简单，成本低廉，具有良好的应用前景。
Description
技术领域
本发明涉及保健食品和药品领域，具体涉及一种同时包含薏苡仁油和β-胡萝卜素两种活性成分的复合脂质体，且该复合脂质体制备工艺简单，具有较好的抗癌抗氧化活性。
背景技术
薏苡仁油作为一种药食同源性功能性油脂，具有广谱的抗癌活性，尤其对肝癌、鼻咽癌、乳腺癌、食道癌等具有较好的疗效。但薏苡仁油水溶性差，生物利用率低；组分中不饱和脂肪酸含量超过70％，易氧化分解产生有害物质，不但影响其功效发挥，且有害健康，其临床应用受到一定的限制。因此，添加一定量的脂溶性抗氧化保护剂的同时，通过载体包埋保护形式转变薏苡仁油物态，是改善薏苡仁油水溶性，提高其生物利用率，保证薏苡仁油安全应用的技术前提。
脂质体技术是一种新型的活性物质包埋技术，制备过程中利用磷脂分子的自组装行为在形成磷脂双分子层的同时，将脂溶性物质包埋于磷脂双分子层中，可提高其稳定性，降低光、氧等对活性成分的破坏，同时，脂质体还具有较好的缓释作用、靶向性、细胞亲和性、无毒性与组织相容性。但脂质体的主要膜材成分-磷脂含有一定量的不饱和脂肪酸成分，易氧化分解产生溶血磷脂等有害成分，降低体系pH的同时易引起包埋物的渗漏，产生聚集、分层现象。因此，现存脂质体制剂为延缓体系氧化，提高稳定性，多采用冷藏方式进行保存，而已有的薏苡仁油脂质体制剂的氧化稳定性也有待提高。另一方面，为了降低脂质体的粒径，提高均一性，在脂质体制备过程中多采用造价较高的高压均质、微射流乳化或超声处理等外力输入方式，工艺复杂，不仅造成生产成本提高，且工业化程度较低。
β-胡萝卜素是胡萝卜素家族中的主要成员，其特殊的富电子共轭体系，可通过猝灭单线态氧和清除自由基发挥较好的抗氧化活性，在抵抗由自由基氧化引起的各种病变：癌症、心脑血管疾病、白内障、衰老等方面有显著的功能，同时也是维护人体健康不可缺少的营养素。另研究表明：自由基是诱发心脑血管疾病，衰老、癌症的重要因素。因此，摄食有效清除自由基的功能性成分是防癌、保健、健康长寿的重要出路。
发明内容
本发明旨在针对现有配方产品的功能及技术缺陷，制备一种同时包埋薏苡仁油和β-胡萝卜素的复合脂质体制剂，该制剂一方面能够给薏苡仁油提供保护屏障，有效减缓其降解速度；另一方面能综合利用β-胡萝卜素的抗氧化作用及薏苡仁油的抗癌作用，提供一种高效抗癌抗氧化复合脂质体制剂。
本发明要解决的另一技术问题是现有薏苡仁油脂质体稳定性差、易氧化，稳定性有待提高。
本发明要解决的再一技术问题是现有β-胡萝卜素脂质体功能单一，抗癌效果不理想。
本发明要解决的又一技术问题是现有技术中以薏苡仁油为有效成分的癌症治疗药物，其抗癌效果有待提升。
本发明要解决的又一技术问题是现有技术中脂质体生产工艺复杂，生产成本较高。
为实现以上技术目的，本发明采用以下技术方案：
一种高效抗癌抗氧化复合脂质体，其特征在于：每25mL复合脂质体中含蛋黄卵磷脂140mg，胆固醇20mg，薏苡仁油6mg，β-胡萝卜素0.6mg，余量是浓度为20mM/L的磷酸缓冲液；
所述制备方法包括以下步骤：
1)取配方量的薏苡仁油、蛋黄卵磷脂和胆固醇，溶解于10mL无水乙醇中；
2)取β-胡萝卜素，制备成浓度为1mg/mL的β-胡萝卜素-二氯甲烷储备液溶液，4℃闭光保存；
3)取步骤2)所得β-胡萝卜素-二氯甲烷储备液溶液0.6mL加入步骤1)所得混合物中，摇匀，得油相；
4)取步骤3)所得油相缓慢注入到恒温43℃且处于磁力搅拌状态下的磷酸缓冲液中，加入完毕后，控制温度和转速不变，继续搅拌20min，随后将样品转移至水浴摇床中，45℃100r/min振荡20min，得脂质体粗乳液；
5)振荡完成后，将样品转移至旋转蒸发仪，于43℃真空条件下整除乙醇及二氯甲烷，得复合脂质体。
作为优选，步骤2)中在所述磷酸缓冲液浓度为20mM/L，pH为6.8。
在以上技术方案中，所述复合脂质体，是指利用脂质体同时包埋薏苡仁油和β-胡萝卜素所得产物。所述蛋黄卵磷脂其磷脂酰胆碱含量≥98％。
本发明提供了一种高效抗癌抗氧化复合脂质体。该技术方案首先对包埋物成分进行了创新性设计，针对薏苡仁油易氧化失活的问题引入了β-胡萝卜素成分，β-胡萝卜素自身的抗氧化作用有助于提升薏苡仁油的化学稳定性，同时对脂质体原料磷脂的自氧化、光氧化现象也具有缓解效果。更为重要的是，β-胡萝卜素本身对人体具有确切的抗衰老、提升免疫力、抗癌等功效，将其与薏苡仁油联用有助于提升抗癌效果，并具有抗氧化功能。
此外，本发明改进了脂质体的制备工艺，通过二次水化的方式：磁力搅拌水化+振荡水化使获得的脂质体分散液更为均匀，后续无需超声或均质处理处理就可获得粒度分布均匀的稳定产品。β-胡萝卜素包封率高达84.46％，平均粒径为186nm，多分散系数为0.104，平均Zeta电位为-30.33。
在以上技术思路的指引下，本发明对薏苡仁油、磷脂、β-胡萝卜素、胆固醇以及所用溶剂的具体用量进行了优化设计，在保证包埋效果的基础上提升了贮藏稳定性和治疗效果，大大改变了常规脂质体制剂只可冷藏的劣势，所制备的复合脂质体室温放置6个月、冷藏放置19个月仍未见分层聚集现象。除此之外，本发明方法所制备的复合脂质体经MTT实验及系列抗氧化实验证实其抗氧化活性及对癌细胞的抑制率均显著高于薏苡仁油脂质体及β-胡萝卜素脂质体。具有较好的应用前景。
附图说明
图1是本发明实施例1所制备的复合脂质体DPPH自由基清除率图：L-CSO：薏苡仁油脂质体；L-βC：β胡萝卜素脂质体；L-βC-CSO:复合脂质体，其中1：1，1：5，1：10，1：15表示β胡萝卜素与薏苡仁油的质量比。
图2是本发明实施例1所制备的复合脂质体对Caco-2癌细胞生长抑制情况：L-CSO：薏苡仁油脂质体；L-βC：β胡萝卜素脂质体；L-βC-CSO:复合脂质体，其中1：1，1：5，1：10，1：15表示β胡萝卜素与薏苡仁油的质量比。
具体实施方式
实施例1
称取卵磷脂140mg、胆固醇20mg、薏苡仁油6mg溶于10mL乙醇，取β-胡萝卜素-二氯甲烷溶液(1mg/mL)0.6mL加入以上乙醇溶液中混匀得油相，将所得油相缓慢注入到25mL20mM/L，pH为6.8的磷酸缓冲液中(恒温43℃且处于磁力搅拌状态)，加入完毕后，控制温度和转速不变，继续搅拌20min，随后将样品转移至水浴摇床中，45℃100r/min振荡20min，得脂质体粗乳液；振荡完成后，将样品转移至旋转蒸发仪，于45℃真空条件下整除乙醇及二氯甲烷，得复合脂质体。
实施例2
称取卵磷脂560mg、胆固醇80mg、薏苡仁油24mg溶于40mL乙醇，取β-胡萝卜素-二氯甲烷溶液(1mg/mL)2.4mL加入以上乙醇溶液中混匀得油相，将所得油相缓慢注入到100mL20mM/L，pH为6.8的磷酸缓冲液中(恒温43℃且处于磁力搅拌状态)，加入完毕后，控制温度和转速不变，继续搅拌20min，随后将样品转移至水浴摇床中，45℃100r/min振荡20min得脂质体粗乳液；振荡完成后，将样品转移至旋转蒸发仪，于45℃真空条件下整除乙醇及二氯甲烷，得复合脂质体。
对比例1
制备方法同实施例1，未添加薏苡仁油。
对比例2
制备方法同实施例1，未添加β-胡萝卜素。
对比例3
制备方法同实施例1，薏苡仁油为0.6mg。
对比例4
制备方法同实施例1，薏苡仁油为3mg。
对比例5
制备方法同实施例1，薏苡仁油为9mg。
将本发明实施例1制得的复合脂质体，对比例1制得的β胡萝卜素脂质体、对比例2制得的薏苡仁油脂质体，对比3、4、5制得的复合脂质体进行DPPH自由基清除率、Caco-2癌细胞生长抑制情况测试，其结果见说明书附图1、2，从图中可以看出本发明制备的复合脂质体，在β-胡萝卜素与薏苡仁油质量比为1：10时，产生的最佳协同作用，可以使DPPH自由基清除率和Caco-2癌细胞生长抑制率显著提高。
Claims (3)
1.一种高效抗癌抗氧化复合脂质体，其特征在于：每25mL复合脂质体中含蛋黄卵磷脂140mg，胆固醇20mg，薏苡仁油6mg，β-胡萝卜素0.6mg，余量为浓度为20mM/L的磷酸缓冲液；
制备方法包括以下步骤：
1)取配方量的薏苡仁油、蛋黄卵磷脂和胆固醇，溶解于10mL无水乙醇中；
2)取β-胡萝卜素，制备成浓度为1mg/mL的β-胡萝卜素-二氯甲烷储备液溶液，4℃闭光保存；
3)取步骤2)所得β-胡萝卜素-二氯甲烷储备液溶液0.6mL加入步骤1)所得混合物中，摇匀，得油相；
4)取步骤3)所得油相缓慢注入到恒温43℃且处于磁力搅拌状态下的磷酸缓冲液中，加入完毕后，控制温度和转速不变，继续搅拌20min，随后将样品转移至水浴摇床中，45℃100r/min振荡20min得脂质体粗乳液；
5)振荡完成后，将样品转移至旋转蒸发仪，于43℃真空条件下蒸除乙醇及二氯甲烷，得复合脂质体。
2.根据权利要求1所述的复合脂质体，其特征在于：所述蛋黄卵磷脂中磷脂酰胆碱的含量≥98％。
3.根据权利要求1所述的制备方法，其特征在于：步骤2)中在所述磷酸缓冲液浓度为20mM/L，pH为6.8。
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