CN104324020A - 一种含有虾青素与白藜芦醇的自微乳颗粒制备方法 - Google Patents
一种含有虾青素与白藜芦醇的自微乳颗粒制备方法 Download PDFInfo
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- CN104324020A CN104324020A CN201410617089.6A CN201410617089A CN104324020A CN 104324020 A CN104324020 A CN 104324020A CN 201410617089 A CN201410617089 A CN 201410617089A CN 104324020 A CN104324020 A CN 104324020A
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Abstract
本发明公开了一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,在40-60℃下,将表面活性剂、辛酸/癸酸甘油三酯及助乳化剂混溶得到空白自微乳;向空白自微乳中加入白藜芦醇及虾青素,搅匀得到含有虾青素与白藜芦醇的自微乳;再向含有虾青素与白藜芦醇的自微乳中加入羟丙基甲基纤维素,搅匀得到混悬状含有虾青素与白藜芦醇的自微乳;最后通过加入微晶纤维素使含有虾青素与白藜芦醇的自微乳变为固态颗粒状粉末,即为含有虾青素与白藜芦醇的自微乳颗粒。通过上述方式,本发明的制备方法简单,制备过程无需特殊的高能耗生产设备,得到的产品有效提高了虾青素及白藜芦醇在水中的溶解度,提高了胃分散及肠道脂解的影响,同时生物有效利用度高。
Description
技术领域
本发明涉及生物制药领域,特别是涉及一种含有虾青素与白藜芦醇的自微乳颗粒制备方法。
背景技术
在古代,“长生不老”是无数人追求的梦想,在现代,依然有无数人希望能够“青春永驻”,在生命科学领域大家把对这个问题的探索称之为“抗衰老的相关研究”,由此可见人们对于抗衰老的研究从古到今都没有停止过,这是一个永恒的话题。众所周知,知其然,才能知其所以然,知道了衰老的机理才能更好的研究抗衰老。
衰老是一个多因素、复杂的综合生理变化过程,是个体成长过程中必然出现的阶段。研究表明,人类自30岁以后,各器官、细胞、生理机能出现随年龄的增大而呈现一个不同程度的下降水平。人类最高寿限是125岁,但是绝大多数人不能活到最高寿限,其原因是由于各种先天因素,或是环境、营养、疾病、心理、社会、不良习惯、体力活动等后天因素造成人类患病率增加而加速了衰老过程。衰老的过程是不可逆的,但如可以延缓衰老就成了研究的热点。经过多年的研究,学者对衰老机制提出了许多学说,在众多学说中,目前大家公认的衰老机理为“自由基学说”。
衰老的自由基学说是Denham Harman在1956年提出的,认为衰老过程中的退行性变化是由于细胞正常代谢过程中产生的自由基的有害作用造成的。生物体的衰老过程是机体的组织细胞不断产生的自由基积累结果,自由基可以引起DNA损伤从而导致突变,诱发肿瘤形成。自由基是正常代谢的中间产物,其反应能力很强,可使细胞中的多种物质发生氧化,损害生物膜。还能够使蛋白质、核酸等大分子交联,影响其正常功能。自由基是具有高度活性的、带有不成对电子的原子或分子,人体内物质在代谢过程中不断产生自由基。适量的自由基为人体生命活动所必须,它可以促进细胞增殖,刺激白细胞和吞噬细胞杀灭细菌,消除炎症,分解毒物。
自由基种类繁多,其中以·O-2和·OH等活性氧自由基最令人瞩目,占体内自由基的95%以上,还包括单线态氧(1O2)、过氧化氢(H2O2)和氮氧自由基。其中·OH几乎是全部氧化反应的中介物质,可与任何部位的大分子发生反应的中介物质,是最活跃、最具有损伤性的自由基。人体自由基的产生有两方面:一是环境中的高温、辐射、光解、化学物质等导致共价键均裂产生的外源性自由基;二是人体内各种代谢反应产生的内源性自由基,内源性自由基是人体自由基的主要来源。其途径主要有以下几条:(1)机体消耗氧的90%以上都是被线粒体所利用的,在生理情况下机体通过线粒体呼吸链内氧化磷酸化途径,Ca2+依赖性磷脂酶A2激发的花生四烯酸代谢途径、黄嘌呤氧化途径,精氨酸NO合成酶途径产生自由基,所以线粒体生成的活性氧在细胞氧自由基的生成中是最主要的;(2)经微粒体混合功能氧化酶系统催化底物产生线粒体外自由基;此外,机体的吞噬细胞、血红蛋白、肌红蛋白也可产生自由基。机体内存在着自由基清除系统,其可以最大限度地防御自由基的损伤。
自由基清除系统包括酶促反应和非酶促反应两部分。酶促反应所需酶有谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(superoxide dismutase,SOD)、过氧化物酶(POP)及过氧化氢酶(catalase,CAT)。非酶促反应的作用物质主要为一些低分子的化合物,是一些抗氧化作用的物质,统称抗氧化剂(antioxidant),主要有谷胱甘肽(GSH)、维生素C、β-胡萝卜素、维生素E、半胱氨酸、硒化物、巯基乙醇等。此外,细胞内部形成的自然隔离,也能使自由基局限在特定部位,如氧化反应产生的自由基主要在线粒体内,线粒体作为独立的细胞器可很大限度地阻止自由基的扩散。
衰老是机体内自由基生成和抗氧化(自由基清除)失衡引起的细胞变性坏死或是凋亡,细胞功能丧失,最后出现整个机体的衰老。因此大家对于抗衰老的研究都是从抗氧化着手,也正是介于此,大家对于有抗氧化功效的成分的研究从未停止过。由于大家坚持不懈的研究,抗氧化的成分一直都在进步:第一代抗氧化的成分是维生素类;第二代抗氧化是β-胡萝卜素、辅酶Q10、SOD之类;第三代抗氧化是花青素、葡萄籽、蓝莓提取物、绿茶素、硫辛酸、番茄红素之类;第四代抗氧化成分主要是天然白藜芦醇、天然虾青素。
白藜芦醇是含有芪类结构的非黄酮类多酚化合物,又称为芪三酚。广泛存在于葡萄、松树、虎杖、决明子和花生等天然植物或果实当中,主要来源于葡萄(红葡萄酒)、虎杖、花生、桑椹等植物。到目前为止至少已在21科、31属的72种植物中被发现。它是许多植物受到生物或非生物胁迫(如真菌感染、紫外照射等)时产生的一种植物抗毒素。白藜芦醇除了能提高植物的抗病性,研究发现它还有有益于人类健康的多种生物学活性及药理作用,深受生物医学界的重视。到目前为止,发现白藜芦醇是肿瘤的化学预防剂,也是对降低血小板聚集、预防和治疗动脉粥样硬化、心脑血管疾病的化学预防剂等。随着研究的深入,其在抗氧化、抗衰老方面的功效研究日益成为国内外专家学者关注的焦点之一。
虾青素(又称变胞藻黄素或虾红素),是类胡萝卜素的一种,为一种较强的天然抗氧化剂。与其他类胡萝卜素一样,虾青素属于一种脂溶性及水溶性的色素,在虾、蟹、鲑鱼、藻类等海洋生物中均可找到。虾青素具有保护皮肤和眼睛、抵抗辐射、心血管老化、老年痴呆和癌症等功效。虾青素因其具有突出的抗氧化能力(β-胡萝卜素的10倍、葡萄籽的17倍、硫辛酸的75倍、叶黄素的200倍、维生素E的1000倍)而备受关注。
白藜芦醇和虾青素按一定比例的组合使用在抗氧化、抗衰老应用方面具有协同增放效应,但是由于白藜芦醇和虾青素均受其自身理化性质的限制,其在水与油中的溶解度均不好,使其生物有效利用度极低。
发明内容
本发明主要解决的技术问题是提供一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,得到的自微乳颗粒可有效提高抗氧化、抗衰老功效并可提高其生物有效利用度。
为解决上述技术问题,本发明采用的一个技术方案是:提供一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,所述制备方法包括的步骤为:
(1)在40-60℃条件下,分别称取100重量份的表面活性剂、5~30重量份的辛酸/癸酸甘油三酯及1~40重量份的助乳化剂充分混溶得到空白自微乳;
(2)在40-60℃条件下,称取3重量份的白藜芦醇及0.1~3重量份的虾青素,加入12~57重量份的所述空白自微乳中,搅拌均匀得到含有虾青素与白藜芦醇的自微乳;
(3)在40-60℃条件下,称取1重量份的羟丙基甲基纤维素,加入9~49重量份的所述含有虾青素与白藜芦醇的自微乳中,搅拌混匀得到混悬状含有虾青素与白藜芦醇的自微乳;
(4)在40-60℃条件下,称取1-3重量份的微晶纤维素,加入1重量份所述混悬状含有虾青素与白藜芦醇的自微乳中,充分混合均匀、研磨、粉碎及过筛,得到含有虾青素与白藜芦醇的自微乳颗粒。
在本发明一个较佳实施例中,步骤(1)中所述表面活性剂为吐温80、聚氧乙烯醚(35)蓖麻油、聚氧乙烯醚(40)氢化蓖麻油、聚乙二醇-8-辛酸/癸酸甘油酯、聚乙二醇-15-羟基硬脂酸酯中的一种或多种。
在本发明一个较佳实施例中,步骤(1)中所述助乳化剂为甘油、1,2-丙二醇、聚乙二醇400中的一种或多种。
本发明的有益效果是:本发明的含有虾青素与白藜芦醇的自微乳颗粒制备方法,该制备方法简单,制备过程无需特殊的高能耗生产设备,得到的自微乳粒颗粒有效提高了虾青素及白藜芦醇在水中的溶解度,提高了胃分散及肠道脂解的影响,同时生物有效利用度高。
具体实施方式
下面将对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅是本发明的一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其它实施例,都属于本发明保护的范围。
实施例一:
本发明提供了一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,所述制备方法包括的步骤为:
(1)在40℃条件下,分别称取100g的吐温80、5g的辛酸/癸酸甘油三酯及1g的甘油充分混溶形成透明均匀的空白自微乳;
(2)在40℃条件下,称取3g的白藜芦醇及0.1g的虾青素,加入12g的步骤(1)得到的空白自微乳中,搅拌均匀形成均匀的透明状含有虾青素与白藜芦醇的自微乳;
(3)在40℃条件下,称取1g的羟丙基甲基纤维素,加入9g的步骤(2)得到的含有虾青素与白藜芦醇的自微乳中,充分搅拌混匀形成混悬状含有虾青素与白藜芦醇的自微乳;
(4)在40℃条件下,称取1g的微晶纤维素,加入1g步骤(3)得到的混悬状含有虾青素与白藜芦醇的自微乳中,充分混合均匀、研钵研磨、粉碎整粒,过200目筛,得到含有虾青素与白藜芦醇的自微乳颗粒。
实施例二:
本发明提供了一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,所述制备方法包括的步骤为:
(1)在50℃条件下,分别称取100g聚氧乙烯醚(35)蓖麻油、15g辛酸/癸酸甘油三酯及20g的PEG400充分混溶形成透明均匀的空白自微乳;
(2)在50℃条件下,称取3g的白藜芦醇及1g的虾青素,加入30g步骤(1)得到的空白自微乳中,搅拌均匀形成均匀的透明状含有虾青素与白藜芦醇的自微乳;
(3)在50℃条件下,称取1g羟丙基甲基纤维素,加入20g步骤(2)得到的含有虾青素与白藜芦醇的自微乳中,充分搅拌混匀形成混悬状含有虾青素与白藜芦醇的自微乳;
(4)在50℃条件下,称取1.5g微晶纤维素,加入1g步骤(3)得到的混悬状含有虾青素与白藜芦醇的自微乳中,充分混合均匀、研钵研磨、粉碎整粒及过300目筛,得到含有虾青素与白藜芦醇的自微乳颗粒。
实施例三:
本发明提供了一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,所述制备方法包括的步骤为:
(1)在60℃条件下,分别称取100g聚乙二醇-15-羟基硬脂酸酯、30g辛酸/癸酸甘油三酯及40g的1,2-丙二醇充分混溶形成透明均匀的空白自微乳;
(2)在60℃条件下,称取3g的白藜芦醇与3g虾青素,加入57g步骤(1)得到的空白自微乳中,搅拌均匀形成均匀的透明状含有虾青素与白藜芦醇的自微乳;
(3)在60℃条件下,称取1g羟丙基甲基纤维素,加入49g的步骤(2)得到的含有虾青素与白藜芦醇的自微乳中,充分搅拌混匀形成混悬状含有虾青素与白藜芦醇的自微乳;
(4)在60℃条件下,称取3g微晶纤维素,加入1g步骤(3)得到的混悬状含有虾青素与白藜芦醇的自微乳中,充分混合均匀、研磨、粉碎整粒及过400目筛,得到含有虾青素与白藜芦醇的自微乳颗粒。
实施例四:
本发明提供了一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,所述制备方法包括的步骤为:
(1)在50℃条件下,分别称取100g聚乙二醇-8-辛酸/癸酸甘油酯、30g辛酸/癸酸甘油三酯及20g1,2-丙二醇充分混溶形成透明均匀的空白自微乳;
(2)在50℃条件下,称取3g的白藜芦醇及1.5g虾青素,加入30g步骤(1)得到空白自微乳中,搅拌均匀形成均匀的透明状含有虾青素与白藜芦醇的自微乳;
(3)在50℃条件下,称取1g羟丙基甲基纤维素,加入19g步骤(2)得到的含有虾青素与白藜芦醇的自微乳中,充分搅拌混匀形成混悬状含有虾青素与白藜芦醇的自微乳;
(4)在50℃条件下,称取1.5g微晶纤维素,加入1g步骤(3)得到的混悬状含有虾青素与白藜芦醇的自微乳中,充分混合均匀、研磨、粉碎整粒及过400目筛,得到含有虾青素与白藜芦醇的自微乳颗粒。
实施例五:
本发明提供了一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,所述制备方法包括的步骤为:
(1)在55℃条件下,分别称取100g聚氧乙烯醚(35)蓖麻油、25g辛酸/癸酸甘油三酯及30g的1,2-丙二醇充分混溶形成透明均匀的空白自微乳;
(2)在55℃条件下,称取3g白藜芦醇与0.5g虾青素,加入17g步骤(1)得到的空白自微乳中,搅拌均匀形成均匀的透明状含有虾青素与白藜芦醇的自微乳;
(3)在55℃条件下,称取1g羟丙基甲基纤维素,加入19g步骤(2)得到的含有虾青素与白藜芦醇的自微乳中,充分搅拌混匀形成混悬状含有虾青素与白藜芦醇的自微乳;
(4)在55℃条件下,称取1.5g的微晶纤维素,加入1g步骤(3)得到的混悬状含有虾青素与白藜芦醇的自微乳中,充分混合均匀、研钵研磨、粉碎整粒及过400目筛,得到含有虾青素与白藜芦醇的自微乳颗粒。
实施例六:
本发明提供了一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,所述制备方法包括的步骤为:
(1)在55℃条件下,分别称取100g吐温80、25g辛酸/癸酸甘油三酯及30g 1,2-丙二醇充分混溶形成透明均匀的空白自微乳;
(2)在55℃条件下,称取3g白藜芦醇磷与0.5g虾青素,加入17g步骤(1)得到的空白自微乳中,搅拌均匀形成均匀的透明状含有虾青素与白藜芦醇的自微乳;
(3)在55℃条件下,称取1g羟丙基甲基纤维素,加入19g步骤(2)得到的含有虾青素与白藜芦醇的自微乳中,充分搅拌混匀形成混悬状含有虾青素与白藜芦醇的自微乳;
(4)在55℃条件下,称取1.5g的微晶纤维素,加入1g步骤(3)得到的混悬状含有虾青素与白藜芦醇的自微乳中,充分混合均匀、研钵研磨、粉碎整粒及过400目筛,得到含有虾青素与白藜芦醇的自微乳颗粒。
本发明的有益效果是:
一、本发明含有虾青素与白藜芦醇的自微乳颗粒制备方法简单,制备过程无需特殊的高能耗生产设备;
二、本发明的含有虾青素与白藜芦醇的自微乳粒颗粒,有效提高了虾青素及白藜芦醇在水中的溶解度,提高了胃分散及肠道脂解的影响;
三、本发明的含有虾青素与白藜芦醇的自微乳颗粒的生物有效利用度高。
以上所述仅为本发明的实施例,并非因此限制本发明的专利范围,凡是利用本发明说明书内容所作的等效结构或等效流程变换,或直接或间接运用在其它相关的技术领域,均同理包括在本发明的专利保护范围内。
Claims (3)
1.一种含有虾青素与白藜芦醇的自微乳颗粒制备方法,其特征在于,所述制备方法包括的步骤为:
(1)在40-60℃条件下,分别称取100重量份的表面活性剂、5~30重量份的辛酸/癸酸甘油三酯及1~40重量份的助乳化剂充分混溶得到空白自微乳;
(2)在40-60℃条件下,称取3重量份的白藜芦醇及0.1~3重量份的虾青素,加入12~57重量份的所述空白自微乳中,搅拌均匀得到含有虾青素与白藜芦醇的自微乳;
(3)在40-60℃条件下,称取1重量份的羟丙基甲基纤维素,加入9~49重量份的所述含有虾青素与白藜芦醇的自微乳中,搅拌混匀得到混悬状含有虾青素与白藜芦醇的自微乳;
(4)在40-60℃条件下,称取1-3重量份的微晶纤维素,加入1重量份所述混悬状含有虾青素与白藜芦醇的自微乳中,充分混合均匀、研磨、粉碎及过筛,得到含有虾青素与白藜芦醇的自微乳颗粒。
2.根据权利要求1所述的制备方法,其特征在于,步骤(1)中所述表面活性剂为吐温80、聚氧乙烯醚(35)蓖麻油、聚氧乙烯醚(40)氢化蓖麻油、聚乙二醇-8-辛酸/癸酸甘油酯、聚乙二醇-15-羟基硬脂酸酯中的一种或多种。
3.根据权利要求1所述的制备方法,其特征在于,步骤(1)中所述助乳化剂为甘油、1,2-丙二醇、聚乙二醇400中的一种或多种。
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