Research Progress on the Composition, Preparation and Promotion of Bioactive Substances Bio-utilization of Self-microemulsion Systems in Food
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摘要: 随着人们健康膳食意识的增强，开发食品功能作用引起了人们的广泛关注。自微乳体系是一种由油相、表面活性剂、助表面活性剂和生物活性物质以一定比例混合后形成的无水预浓缩体系。通过自微乳体系荷载食品生物活性物质可改善其生物利用度，并充分发挥其生理及药理活性。本文系统综述了自微乳的基本性质、组分及制备方法，整理了近年来自微乳体系在食品领域促进生物活性物质生物利用的应用实例，为自微乳体系在食品领域的推广应用提供了参考。Abstract: With the enhancement of people's awareness of healthy diet, the innovation of food function has become a hot topic. Self-microemulsion system is an anhydrous pre-concentration system which contains a mixture of oil phase, surfactants, co-surfactants, and bioactive substances in a certain proportion. Food bioactive substances can be loaded in self-microemulsion system, which can improve the bioavailability of food bioactive substances. Moreover, it also fully exerts the physiological and pharmacological activities of food bioactive substances. In this paper, the basic properties, components and preparation methods of self-microemulsion are systematically reviewed. Further, the application examples of self-microemulsion system to promote bioactive substances bio-utilization in food field in recent years are summarized, which provides a reference for the application of self-microemulsion system in food field.
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生物活性物质具有如抗氧化、抗炎、抗菌等多种健康功效，若将其作为膳食补充剂加入食品中，可赋予食品更多的功能特性。但大多生物活性物质水溶性差、化学性质不稳定，生物利用度低，而无法充分发挥其生理及药理活性[1−2]。目前开发出了许多递送系统，以促进生物活性物质的吸收，如将非生物活性前体和生物活性物质进行连接的化学修饰法、协同给药法、运载体包埋法等[3]。但化学修饰法会改变原物质的生物活性、诱发食品安全问题[4]；协同给药法中协同物质的选择局限性太大，会限制其在食品中的应用[5]。因此具有较高安全性以及材料种类可选择性强的运载体包埋法受到了广泛关注[6]，其中自微乳是提高生物活性物质口服生物利用度的一种理想且有前景的方案。自微乳体系由油、表面活性剂、助表面活性剂和生物活性物质各向同性混合物组成，当与水或其他溶剂介质混合时，可以迅速形成微乳液[7]。与其他递送体系相比，自微乳更为突出的优势在于：首先，自微乳热力学、动力学稳定[8]，储存稳定性较好[9]；其次，自微乳由于液滴粒径小，被人体吸收时在体内形成的界面面积大，能够促进食物中生物活性物质的更快释放[10]，易于穿透胃肠道被吸收[11]；此外，自微乳所需的制造设施简单，如搅拌器及用于大规模生产的液体灌装设备[12]，成本低，制造方便。
自微乳的形成机制理论主要包括界面膜-液晶理论、增溶理论、表面张力学说和热力学理论，其中较成熟的理论是表面张力学说和热力学理论[13]。表面张力学说认为，自微乳中表面活性剂含量越高，油水界面张力越低，当表面活性剂浓度上升到一定程度时，在助表面活性剂的作用下产生混合吸附，界面张力出现负值，为了达到热力学平衡，体系自发分散为微细的液滴[13]。而热力学理论认为，自微乳过程中的吉布斯自由能与表面活性剂降低油/水界面张力和体系在分散过程中熵的增加密切相关。∆Gf=γ∆A−T∆S。∆Gf是体系的吉布斯自由能，γ是体系的油水界面张力，∆A是自微乳过程中体系表面积的改变，∆S是体系分散过程中熵值的改变，T是温度。分散过程中，熵变远大于增加表面积所需要的能量时，自微乳就会自发形成[14]。
虽然自微乳体系早期在医药方面应用广泛[15]，被称为“自微乳给药系统”，但是近年来自微乳也被广泛应用于食品领域，是极具开发应用潜力的功能食品制剂。然而，尚未见自微乳体系在食品中应用的详细综述报道。因此，本文主要总结食品中自微乳体系的组成及制备，并系统综述自微乳体系促进生物活性物质生物利用的应用研究，为自微乳体系的构建及其在食品中的进一步应用提供理论支撑和思路对策。
1. 自微乳体系的组成
如图1所示，自微乳体系是由生物活性物质、油相、表面活性剂、助表面活性剂同性混合物组成的无水预浓缩系统，大多为液体或固体制剂，在胃运动的轻微搅拌下，用水介质（如胃肠道液体）稀释后形成粒径小于100 nm的透明水包油（O/W）微乳液[16]。而微乳液由油、水、表面活性剂、助表面活性剂制备，由于表面活性剂胶束在加入大量油后达到饱和状态，胶体分散的自由能小于分离相。因此，当油、表面活性剂和助表面活性剂全部混合在一起时，微乳自发形成，几乎不需要外界能量，热力学稳定[7]。与微乳液相比，属于无水体系的自微乳可以减少溶剂对反应平衡和反应速度的物理及化学影响，从而提高功能性食品的稳定性，具有更加吸引人的商业可行性和消费者依从性。
1.1 油相
在自微乳体系中油相起着至关重要的作用，它不仅能被规定量的表面活性剂迅速乳化，而且所形成的微乳液粒径较传统乳液更小，还可将亲脂性的生物活性物质溶解在体系内[17]。油相占体系总量的10%，在自微乳体系中的主要作用是溶解疏水的活性成分，从而提高疏水活性成分的载体能力和生物利用度[18]。
在自微乳体系中，通常油相的选择依赖于其对生物活性物质的溶解能力以及油相与其它成分配伍后的自乳化效果[19]（自乳化效果指自微乳体系自发形成分散相粒径均一的乳滴的能力，以自乳化后体系的色泽、乳化时间、乳化粒径为指标，色泽越澄清、乳化时间越短、乳化粒径越小显示自乳化效果越好[20]），要求油相以较少的用量溶解生物活性物质，即使在低温储藏条件下生物活性物质也不会析出，且容易被自微乳体系中的表面活性剂所乳化[19]。李学艳等[21]选取不同种类的油相制备含虾青素的雨生红球藻粉自微乳，发现大豆油对于虾青素的溶解率相比其它油相高，可达到54.68 mg/g，但与其它成分配伍后的自乳化性能不好，因此选取溶解度高且配伍后自乳化性能较好的三乙酸甘油酯作为油相。
目前使用的油相主要分为中链甘油三酯（如椰子油、棕榈籽油）、长链甘油三酯（如玉米油、大豆油、橄榄油、花生油、芝麻油、葵花油、蓖麻油）以及混合的甘油单酯、甘油二酯、甘油三酯（如Imwitor® 988，Imwitor®308）[22]。一般中链甘油三酯是制备体系的首选油相[23−24]，因为与长链甘油三酯相比，中链甘油三酯的氧化损失较少，溶剂容量较大[25]。陈倩等[26]选用中链甘油三酯、油酸乙酯、橄榄油作为不同油相制备葛根总黄酮自微乳化半固体骨架胶囊，将不同油相与不同表面活性剂、助表面活性剂进行配伍，发现中链甘油三酯作为油相获得的体系澄清度高，蓝色乳光强，且安全性高。
1.2 表面活性剂
表面活性剂能使目标溶液表面张力显著下降，由极性基团（亲水基团）和非极性基团（亲脂基团）所组成[27]，一般分为离子型、非离子型以及两性型，其中非离子型表面活性剂毒性低且HLB值较高（HLB值用来判别表面活性剂的亲水或亲油程度，HLB值较高代表亲水性较强），被广泛用于自微乳体系的具体制备，溶解疏水成分[28]。表面活性剂占体系总量的50%[18]，在体系中的主要作用是通过增加肠道通透性或增加肠膜与脂质之间的亲和力促使生物利用度的提高，其作用机制是通过进入细胞膜破坏脂质双分子层的结构组织，从而导致渗透增强[29]。
实验对表面活性剂的安全性以及HLB值有一定要求，只有少数表面活性剂被允许用于食品中，并且表面活性剂在特定条件下会产生毒性。通过食品认可的表面活性剂，可以制成完全可食用和可稀释的配方[29]，最常使用的食品级表面活性剂有聚氧乙烯20油酸酯（吐温80）、维生素E TPGS和聚氧基35蓖麻油[30]。例如，Warisnoicharoen等[31]发现Brij97（聚氧乙烯-10-油基醚）单独使用或与低分子量的油混合使用，以及超过其临界聚集浓度时都有毒性。Brij97与高分子量油（如Miglyol 812和大豆油）混合仅在高于临界聚集浓度时才产生毒性。一般情况下HLB值的范围在9~20，如Tween80、RH40、波洛沙姆等[19]，HLB值过高时，自微乳体系的递送效果会减慢[19]。因此开发绿色安全、HLB值较高的食品级表面活性剂具有极大研究价值。
研究者发现复合的表面活性剂能使自微乳获得更好的物理稳定性。Yang等[16]分别制备以D-α-生育酚聚乙二醇丁二酸酯为单一表面活性剂和以D-α-生育酚聚乙二醇丁二酸酯、吐温20为混合表面活性剂的自微乳体系荷载大豆苷元，在4 ℃下保存3个月后，混合表面活性剂自微乳保持清澈透明的液体，而单一表面活性剂自微乳则变成带蓝色乳白色的半透明液体，表明含混合表面活性剂的自微乳稳定性优于含单一表面活性剂的自微乳。Li等[32]使用吐温20和聚氧乙烯蓖麻油EL1:1混合作为复合表面活性剂制备自微乳体系，递送氟比洛芬，发现复合使用两种表面活性剂与单独使用其中任一种表面活性剂相比，稀释后的微乳粒径较小（10~11 nm），且载药量增加对微乳粒径影响不大。不同载药量下粒径无明显变化。用不同水介质（水、模拟胃液或模拟肠液）稀释也没有改变微乳的粒径。
1.3 助表面活性剂
自微乳体系中较高浓度的表面活性剂刺激人体胃肠道，带来毒性，因此需要添加合适的助表面活性剂降低表面活性剂浓度。在自微乳体系中，助表面活性剂的比例在20%~50%之间，在体系中的作用一是为表面活性剂薄膜提供所需的灵活性和弹性，稳定内部相，二是提高体系的运载能力，减少表面活性剂用量，降低体系对胃肠道的刺激[33]。常用的助表面活性剂有短链醇、有机氨、单双烷基酸甘油酯和聚氧乙烯脂肪酸酯等[34]，其中乙醇是目前被允许并在食品中使用广泛的助表面活性剂，但它可能不适合儿童或其他对酒精不耐受的人群。因此还要不断深入研究，扩大助表面活性剂在食品中的应用范围。
在自微乳体系中，助表面活性剂的选择主要依赖于其碳链的长短，通常直链优于支链，长链优于短链，接近表面活性剂链长或表面活性剂链长等于助表面活性剂与油相链长之和时效果较好[35]。凡小燕[36]制备橙皮苷自微乳，选用不同碳链的助表面活性剂，发现PEG400相比丙三醇和1,2-丙二醇形成的自微乳区域较大。
助表面活性剂和表面活性剂的协同作用促进微乳形成并增加其稳定性，起到助乳化作用[33]，这是由于助表面活性剂与表面活性剂共同形成的复合界面膜，降低了界面张力及电荷排斥力，增强了界面膜的流动性和柔顺性[19]，形成助表面活性剂从界面膜到连续相和分散相的交换，以及界面膜和水之间的表面活性剂交换的动态平衡[27]。
1.4 自微乳组分的配方优化
合适的配方可以增加体系的载体能力，减少对人体胃肠道的刺激，如开发具有高乳化性能、高安全性的成分作为表面活性剂及助表面活性剂。自微乳体系表征与各组分的性质及用量密切相关。Chen等[37]以乳清分离蛋白、大豆黄酮及表面活性剂制备自微乳体系，发现自微乳各组分间存在相互作用并且相互影响，D-α-生育酚聚乙二醇琥珀酸-吐温20与大豆分离蛋白配合使用，能够制备稳定性较好的微乳液。
伪三元相图是将3个顶点所代表的混合物替代三元相图中的纯物质，确定有效的成乳区域，是研究微乳形成区域的基础工具[38]。如图2所示，自微乳一般以油相、水相、表面活性剂与助表面活性剂混合物作为3个顶点，样品在图中标记为点，这些点所覆盖的区域就是自微乳区域（图中灰色区域）。自微乳区域越大，说明在水性介质中稀释的潜能越大，受环境及药物的影响越小。研究通常构建伪三元相图确定自微乳体系的区域及其组分之间的最优浓度比例[39]。黎鹏等[40]根据配伍相容性及伪三元相图结果，分别选择肉豆蔻酸异丙酯、聚山梨酯80和异丙醇作为自微乳的油相、表面活性剂和助表面活性剂，且该自微乳体系具有良好的抗炎镇痛作用。
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图 2 模拟的自微乳体系伪三元相图Figure 2. Pseudo ternary phase diagram of simulated self-microemulsion system如图3所示，通过伪三元相图初步筛选空白自微乳的比例，在此基础上再利用系统的实验设计方法，如Box-Behnken设计（BBD）、中心复合设计（CCD）探究配方和工艺参数对液滴尺寸、乳化率等响应变量特征的影响，以优化自微乳配方，选中配方后进行进一步的体外表征与体内测试[41]。
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图 3 制备自微乳的实验设计方案流程图Figure 3. Flow chart of experimental design scheme for preparing self-microemulsion一些研究在自微乳体系中加入辅料，提高体系稳定性。毛昕宇[42]在虾青素固体自微乳体系中探究了大豆粉末磷脂与酪蛋白酸钠两种保护剂对其自微乳稳定性的影响，发现与未加保护剂的样品组相比，自微乳在自然光及特定温度下放置30 d后的虾青素保留率由原本的低于40%提高至50%以上，说明加入保护剂可提高自微乳的长期化学稳定性，且两种保护剂当中大豆粉末磷脂的保护作用更佳。另外一些脂溶性抗氧化剂，如α-生育酚、β-胡萝卜素、丁基羟基甲苯、丁基羟基茴香醚或没食子酸丙酯也可以加入到自微乳体系中，保护不饱和脂肪酸链或生物活性物质免受氧化[43]。不过辅料的使用具有很大局限性，需要考虑加入后消费者对于食物的接受度及辅料安全性的问题，另外只有特定的辅料组合才能在自微乳体系中起到特定作用。
2. 自微乳的制备方法
传统自微乳体系一般是液体制剂，其制备方法通常使用涡流混合器将油、表面活性剂与助表面活性剂混合（2~3 min），直到系统稳定均匀，密封保存于室温（25 ℃）下。将预混液添加到固定质量的水相中（50~100 mL），轻度搅拌促进混合（反转法手动或磁力搅拌器或涡流），即可观察到透明微乳液的形成。自微乳自发分散成球状物，不需要任何外部能量[44]。配方中使用的高浓度乳化剂（表面活性剂与助表面活性剂）将表面张力降低到几乎为零的水平，从而促进内部相极小球状物的形成[45]。微乳液和自微乳体系的制备过程非常相似。与自微乳不同的是，微乳液是通过滴定法制备的，需要在制备自微乳的方法上增加一个步骤。将油、表面活性剂和助表面活性剂进行预混合后，在磁力搅拌器的连续搅拌下以滴定方式加入水，直至形成透明微乳液[7]。
传统自微乳由于其液体剂型的特点[6]，在食品应用中会存在剂型单一、难以携带[46]、成分之间容易发生相互作用、成本较高问题[47]，另外液体制剂化学性质不稳定，长时间贮藏后的转化是不可逆的，会导致沉淀的生成[48]。随着制备工艺的不断创新和材料技术的迅速发展，在此基础上诞生了自微乳的固化方法，即将液体自微乳转换成固体自微乳的过程及方法，如黄娟等[49]利用二氧化硅作为吸附材料，制备固体化的二氢杨梅素固体自微乳，通过体外释放发现释放10 h时固体自微乳的二氢杨梅素累积释放率仍低于液体自微乳约15%，说明固体自微乳受二氧化硅阻碍，释放时间较长，对二氢杨梅素的释放起到控制和减缓释放的作用，有效提高二氢杨梅素的生物利用度。图4为自微乳的固化工艺示意图，自微乳的固化有效解决因液体制剂形式应用在食品中存在的不足，降低生产成本、改善稳定性、提高安全性等。早期固化方法有固体载体直接吸附法[50]、喷雾干燥法[51]、冷冻干燥法[52]、离子凝胶化技术和液固压缩技术[53]等。近些年，一些新型的固化方法为提高自微乳体系的性能提供了新思路。如挤出滚圆法是目前比较常见、新颖的一种制备固体自微乳的方法，将液态自微乳吸附到固体载体上制成固体自微乳颗粒，将其与稀释剂、黏合剂、崩解剂等辅料混合均匀成塑性软材，经挤出设备挤出后变形再断开，在转盘上经高速旋转滚圆，形成颗粒大小均匀的微丸[54]，这种方法效率较高、粒径分布范围较集中、乳化效果好、固体制剂较稳定[54]。球晶技术也是目前固化自微乳的新方法，指的是液体自微乳体系改变溶剂及反应条件而进一步析晶、聚焦，形成球型颗粒的一种技术[55]，具有简化工序、载体量大、稳定性强的特点[15]。
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新型自微乳体系除固体自微乳以外，还包括过饱和自微乳与正电荷自微乳[56]。过饱和自微乳是在传统自微乳配方中加入过饱和促进剂，过饱和促进剂在大量水稀释过程中抑制生物活性物质的沉淀，从而使生物活性物质加水后溶解为分子态，减少表面活性剂的用量[57]。正电荷自微乳是在现有自微乳配方的基础上增加一些阳离子物质（如硬脂酰胺、油胺、溴化十六烷基三甲铵和壳聚糖等），使自乳化后的乳滴表面带正电荷，而胃肠道上皮细胞带负电荷，这些带正电荷的乳滴加速制剂和胃肠道上皮细胞的静电吸附，提高机体对生物活性物质的吸收[58]。
3. 自微乳促进生物活性物质的生物利用
3.1 促进生物活性物质在体内的吸收
食品中的生物活性物质经过人体胃肠道时，会发生一系列复杂的物理、化学以及生物环境的变化（如pH、离子强度、机械动力等），导致生物活性物质化学结构不稳定[4]，从而降低生物活性物质的生物利用度。作为递送体系的自微乳通过延长营养素在胃部的滞留时间、增强生物活性物质的水溶解度、设计良好的控制释放机制、促进淋巴对生物活性物质的吸收、维持肠膜流动性等一系列途径，维持生物活性物质在人体内的稳定性，从而提高其生物利用度[59]。
自微乳体系在人体内吸收利用的具体作用机制如下：体系在人体胃肠道中轻微蠕动，自发得到的微小粒子表面积很大[60]，增加了人体胃肠道的上皮细胞渗透性；自微乳表面张力极低以及表面的亲水性，导致微乳液的液滴比较容易地通过肠腔粘膜上侧的水化层，使得食物中的生物活性物质直接接触胃肠道上皮细胞，从而促进体内生物活性物质的吸收；自微乳中的表面活性剂可以抑制P-糖蛋白对生物活性物质的外排作用，进一步增强人体对生物活性物质的吸收（外排作用指细胞内物质通过形成小泡从细胞内部逐渐转移到细胞膜附近，与质膜融合而把物质排出细胞的方式）；体系中的脂质成分在胰酶及胆汁的作用下发生脂解，得到更小粒径的微乳乳滴和胆盐胶束，促进生物活性物质的跨膜吸收转运，引起生物活性物质的进一步溶解，另外脂质成分还使微乳液液滴通过肠道淋巴管吸收，克服首过效应（首过效应指某些生物活性物质进入胃肠道，在尚未吸收进入血循环前，在肠粘膜和肝脏被灭活代谢，而使进入血循环的活性物质减少的现象），提高大分子物质的口服吸收[61]。谭亚男等[62]制备不同比例的卤泛群自微乳体系，以清醒的二插管大鼠为动物模型，建立高效液相色谱法检测淋巴中卤泛群含量，发现可以通过改进体系配方增加生物活性物质的淋巴转运量，提高其生物利用度。梁鑫淼等[63]使用吐温80:聚乙二醇-400:肉豆蔻酸异丙酯=14:7:9比例制备的皮诺素磷脂复合物自微乳粒径小，分散均匀，体外释放度高，且可以提高斯皮诺素的肠吸收。
3.2 提高生物活性物质的抑菌作用
自微乳体系通过封装含有抑菌活性的生物活性物质，从而起到抑菌作用，提高食品质量，延长产品保质期。EL-Sayed等[64]采用气相色谱-质谱联用技术对大蒜精油化学成分进行表征，分析在不同递送体系下（有机溶剂、乳化与自微乳）的抑菌性能，发现大蒜精油在粒径为10.1 nm的自微乳中具有更好的抑菌活性。Almasi等[65]制备含百里香精油自微乳体系的海藻酸钙抗菌膜，发现该体系对牛肉中的金黄色葡萄球菌与大肠杆菌具有良好的抗菌活性。Almasi等[66]利用制备的该薄膜进行了新实验，发现封装抗菌精油的自微乳是很好的抑菌剂，该薄膜能有效控制高水分食品（肉类及鱼类）的微生物质量，提高食品保质期。
自微乳体系的具体抑菌作用是通过生物活性物质的亲脂性穿透细胞膜与细胞器膜，造成细胞器损伤，最终导致真菌死亡[67]。另一种是食品中的某些活性成分破坏了细胞的磷脂双分子结构以及其生长所需能量的来源，从而造成细胞完整性的损伤[68]。由于细菌细胞壁结构不同，因此自微乳体系对不同种类的细菌表现出不同程度的抑菌作用[69]。另外自微乳体系中表面活性剂成分的含量也直接影响其抑菌效果的强弱，即表面活性剂含量越高，抑菌效果越弱[70]。肖小年等[71]通过考察原辅料相溶性以及绘制伪三元相图，获得最优配方的大蒜油自微乳。肖小年等[72]接着利用得到的大蒜油自微乳对食品常见腐败菌的抑制作用进行研究，发现对真菌的抑菌作用最强，该体系通过负载大蒜油，促使腐败菌细胞膜及细胞壁受损，引发菌体细胞内谷丙转氨酶、碱性磷酸酶、谷草转氨酶的泄露以及离子渗出，扰乱细菌内部的酶体系，抑制细菌的生长繁殖，从而导致菌体死亡。
3.3 发挥生物活性物质的保健功能
随着人们对养生保健的意识越来越深入，各种保健食品的开发也有了很大的发展。生物活性物质[73]，包括维生素、类黄酮、甾醇类、萜类、脂类、蛋白质等[74]，具有多种生理和药理活性[75]，可用于预防某些慢性疾病，如心脏病、炎症、自身免疫性疾病等，或改善人的情绪、活动等[76]。通过自微乳包埋生物活性物质制备的自微乳体系，可以在不对食品保质期、安全性、质地、味道、外观产生不利影响的条件下，克服生物活性物质在人体胃肠道内停留时间短、溶解度差、渗透性低以及稳定性差等问题，甚至还可以减少刺激性或毒性等的不良反应[77]，最终提高生物活性物质的生物利用度，使食品充分发挥出生理与药理活性，从而达到保健功能，这种功能在目前食品应用中较为常见。毛昕宇[42]将虾青素固体自微乳体系与抹茶粉混合制备得到虾青素固体茶，对虾青素固体茶的长期稳定性进行考察，发现28 d内虾青素的保留率在70%以上，成功制备了虾青素稳定存在并具有减缓衰老、改善运动机能等功能的固体茶。金栋等[78]制备不同粒径的灵芝孢子油自微乳体系，以灵芝孢子油中有效成分麦角甾醇为指标性成分，采用高效液相色谱法对灵芝孢子油自微乳进行质量评价，发现该自微乳稳定可控地发挥了麦角甾醇提高免疫力的作用。Xu等[79]制备负载[6]-姜辣素的自微乳系统，通过[6]-姜辣素在大鼠体内的药代动力学分析，发现自微乳体系可以延长血浆循环，使得口服生物利用度较游离的[6]-姜辣素提高6.58倍，发挥[6]-姜辣素缓解镇痛以及抗焦虑的活性。
这种从天然营养来源中分离得到的生物活性物质，能够在温和的长期环境预防甚至治疗疾病，与其它同功效药品相比，其毒性以及不良副作用都相对较少。Chen等[80]研究了纳米囊化白藜芦醇在自微乳系统中的应用，采用DCFH-DA法和CCK-8法检测出该自微乳体系相比游离的白藜芦醇具有更强的抗氧化能力和更小的细胞毒性，可以增强白藜芦醇预防心血管疾病的保健作用。Lyu等[81]制备d-α-生育酚聚乙二醇1000琥珀酸-藜叶皂素自微乳体系以增强二氢杨梅素的吸收率，通过肠道微生物组相互作用分析和肝脏非靶向代谢组学技术，发现含二氢杨梅素的自微乳通过影响甘油磷脂代谢、鞘脂代谢、泛酸和辅酶A生物合成等途径可以减轻高脂饮食引起的肥胖和非酒精性脂肪肝病。Chou等[82]制备5-去甲基橙皮苷自微乳体系，建立结肠癌异种移植动物模型以进行免疫组织化学分析，发现与5-去甲基橙皮苷悬浮组相比，负载5-去甲基橙皮苷的自微乳体系通过增加5-去甲基橙皮苷的口服吸收以及增强其代谢产物而具有明显的抗癌作用，成功证明5-去甲基橙皮苷自微乳体系是一种有前途的癌症预防营养制剂。
4. 总结与展望
提高难溶性生物活性物质的生物利用度，促进生物活性物质的体内吸收以保证发挥它们最大的生理药理活性是功能食品领域研究的重点。自微乳体系作为新型递送系统，具有优良的性能，在提高难溶性生物活性物质生物利用方面有着广阔的应用前景。然而，目前关于评估自微乳潜在风险和对人体毒性的研究还不够充分，需要进一步研究，以制备含有生物活性物质的商业功能食品。为了设计和开发基于自微乳的潜在创新食品，需要进行以下研究：a.从天然来源中开发新型表面活性剂；b.研究自微乳成分与其它食品成分之间可能的相互作用；c.设计自微乳的体外预测模型并在合适的动物模型中进行体内测试；d.产品储存稳定性研究。在未来通过广泛的研究，自微乳体系的改进将提供新型的输送系统，将生物活性物质引入食品，将更安全、更有效的功能食品引入市场。
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图 2 模拟的自微乳体系伪三元相图
Figure 2. Pseudo ternary phase diagram of simulated self-microemulsion system
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图 3 制备自微乳的实验设计方案流程图
Figure 3. Flow chart of experimental design scheme for preparing self-microemulsion
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