CN108578370A - 叶黄素/叶黄素酯微粒及其制备方法 - Google Patents
叶黄素/叶黄素酯微粒及其制备方法 Download PDFInfo
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- CN108578370A CN108578370A CN201810352049.1A CN201810352049A CN108578370A CN 108578370 A CN108578370 A CN 108578370A CN 201810352049 A CN201810352049 A CN 201810352049A CN 108578370 A CN108578370 A CN 108578370A
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- Prior art keywords
- lutein
- ester
- particle
- lutein ester
- wall material
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Abstract
叶黄素/叶黄素酯微粒及其制备方法，通过将含有叶黄素和/或叶黄素酯、壁材以及助乳化剂的原料混合物在低温条件下制备成粒径不超过1微米的纳米乳液，再喷涂至蔗糖‑淀粉颗粒上制备；所述的壁材是纤维素衍生物。本发明的上述制备方法克服了叶黄素/叶黄素酯原料在制剂化过程中固有的缺陷，避免了高温熔融晶体或溶剂熔融晶体所带来问题；通过纤维素衍生物和助乳化剂的选择与组合，有效解决了叶黄素/叶黄素酯难于乳化的问题。也因此获得有效组分含量高达25％，并具有极其优异的保存稳定性的叶黄素/叶黄素酯微粒产品。该微粒产品可以根据需要应用于制备食品、药品、保健品、功能食品等。
Description
技术领域
本发明涉及一类类胡萝卜素制剂及制备方法。
背景技术
类胡萝卜素因具有较强的抗氧化等功能，市场需求量不断增加。其中万寿菊来源的叶黄素、叶黄素酯和玉米黄质具有独特的眼保护功能，可防止紫外线的损伤。同时可作为强氧化剂抑制活性氧自由基活性，起到护肤保心和增强免疫的作用。我国卫生部公告已经确立批准叶黄素酯、玉米黄质为功能性新资源食品。
目前，叶黄素及其酯和玉米黄质主要应用于眼保护的功能食品、膳食补充剂，以软胶囊和微囊粉的形式为主。近几年来，食用方便的片剂产品不断受到消费者的认可，但压片所使用的原料微囊粉存在机械强度低、稳定性较差的缺点。因此能够应用于打片的具有较高机械强度的叶黄素/叶黄素酯微粒成为压片原料首选。传统制备叶黄素/叶黄素酯微粒的工艺通常选用植物油和叶黄素/叶黄素酯晶体熔融的工艺，将叶黄素/叶黄素酯乳化，再用壁材包埋，该技术在高温熔融时，叶黄素/叶黄素酯含量会大大降低，增加了成本。
例如，CN 201010182547.X中公开的叶黄素酯微粒的制备方法，将叶黄素酯和植物油(大豆油)及抗氧化剂(VE/TBHQ/迷迭香/VC)按照1:2-10:0.01-0.03的比例混合后加热到60-90℃来制备，这种方法不仅会增加油相的载量，造成包埋率低，产品不稳定的缺点，同时高温下的搅拌，也会增加叶黄素酯的降解风险。类似的情况还有CN 201410030538.7、CN201410349554.2和CN 201510511023.3。
叶黄素及叶黄素酯制剂化过程中多使用乳化剂，尽管WO 2016124784A1、WO2016124783A1、WO2016124785A1等在先公开提供了不使用乳化剂的制备方法，分别应用于阿拉伯胶、猪明胶、鱼明胶等保护性壁材体系中。但是不可避免地，这些技术方案中仍然需要将叶黄素及其酯和植物油进行高温熔融后制剂，存在同样问题。
CN 201310117340.8公开了一种纳米叶黄素酯制剂的方法：加热条件下包裹材料(环糊精/羟甲基纤维素钠/羟丙基纤维素钠/聚维酮/聚乙二醇/甘露糖/半乳糖/胆酸)溶于有机溶剂中，叶黄素酯加热溶解在同种有机溶剂(丙酮/甲醇/乙醇/乙酸乙酯)中，在将叶黄素酯乳化，挥干溶剂成型的方法制备叶黄素酯纳米制剂。但是叶黄素酯作为新资源食品，却在制剂化过程中使用有毒的有机溶剂，将大大限制其在食品领域的应用。同样，CN201210458891.6也使用了药用级辅料及有机溶剂大大限制了叶黄素/叶黄素酯的应用。
CN 200610152617.4公开了一种食品级叶黄素水溶性干粉的制备方法：叶黄素与低沸点易挥发的有机溶剂混合，加热溶解后加入水相进行乳化，挥干溶剂进行叶黄素干粉的制备。该方法使用大量毒性有机溶剂，对环境及工作人员造成伤害，并非优选的制备方法。
鉴于以上制备叶黄素/叶黄素酯制剂时的诸多问题，如何在更加温和环保的条件下制备稳定且高质的叶黄素/叶黄素酯微粒制剂，是本申请研究的重点。
发明内容
本发明目的之一在于提供一种含量高、保存稳定的叶黄素/叶黄素酯微粒，通过将含有叶黄素和/或叶黄素酯、壁材以及助乳化剂的原料混合物在低温条件下制备成粒径不超过1微米的纳米乳液，再喷涂至蔗糖-淀粉颗粒上制备；所述的壁材是纤维素衍生物。
相应地，本发明也提供上述叶黄素/叶黄素酯微粒的制备方法，包括下述步骤：
(1)将原料混合物在10-35℃条件下制备成粒径不超过1微米的纳米乳液；
所述的原料混合物含有叶黄素和/或叶黄素酯、壁材以及助乳化剂；
所述的壁材是纤维素衍生物；
(2)将步骤(1)制得的纳米乳液喷涂至蔗糖-淀粉颗粒上。
本发明的上述制备方法克服了叶黄素/叶黄素酯原料在制剂化过程中固有的缺陷，避免了高温熔融晶体或溶剂熔融晶体所带来问题；通过纤维素衍生物和助乳化剂的选择与组合，有效解决了叶黄素/叶黄素酯难于乳化的问题。也因此获得有效组分含量高达25％，并具有极其优异的保存稳定性的叶黄素/叶黄素酯微粒产品。该微粒产品可以根据需要应用于制备食品、药品、保健品、功能食品等。
具体实施方式
本发明提供一种叶黄素/叶黄素酯微粒及其制备方法，所述的方法通过将含有叶黄素和/或叶黄素酯、壁材以及助乳化剂的原料混合物在低温条件下制备成粒径不超过1微米的纳米乳液，再喷涂至蔗糖淀粉颗粒上。
上述技术方案中，所述的低温条件按照本领域通常理解，可限定于10-35℃，优选25-30℃。制备纳米乳液也可以采用现有技术中常用方法，这些方法可举例但不限于胶体磨分散、高压均质的方法。所述的蔗糖淀粉颗粒作为载体，可以根据产品的需求按照现有技术的记载制备。本发明中，使用淀粉与蔗糖按照质量比10：90～30：70的混合物通过制粒机制备的蔗糖淀粉颗粒，粒度要求在150～425微米之间。采用本发明的技术方案可以制得含量为1-25％，并且耐储存的优质叶黄素/叶黄素酯微粒。
进一步具体地描述，上述本发明的叶黄素/叶黄素酯微粒中，所述及的壁材是纤维素衍生物。具体地，所述的壁材是羟丙甲纤维素、甲基纤维素、乙基纤维素、羧甲基纤维素钠中的一种或几种的混合物。最为优选的实施例中的壁材是羟丙甲纤维素。
而该优选技术方案中，壁材限定的技术手段与助乳化剂的搭配选用构建更为优选的技术方案。本发明所述的助乳化剂是黄原胶、普鲁兰多糖或二者的混合物。最优选普鲁兰多糖。黄原胶和普鲁兰多糖均为出芽短梗霉发酵所产生的胞外水溶性粘质多糖，可以商品购得。本发明中所使用的黄原胶是选购自梅花生物科技集团股份有限公司1200-1600厘泊规格，普鲁兰多糖是选购自梅花生物科技集团股份有限公司PLI-10型号，羟丙甲纤维素选自安徽山河药用辅料股份优选公司，SH-E50型号、SH-E15型号、SH-E5型号、SH-E3型号，聚葡糖选自翊圣生物公司15000分子量型号。
进一步优选的技术方案中，所述的壁材与助乳化剂按照特定比例混合。具体实施方式中，壁材和助乳化剂的质量比为5-20:1。优选5-15:1，更优选8-13:1。另一方面，所述的壁材与助乳化剂的用量总和为微粒质量的10-20％。优选13-18％，更优选15-17％。
本发明所述的技术方案中，理论上所有类胡萝卜素类物质都可用于本发明中。优选万寿菊来源的万寿菊来源的叶黄素、玉米黄质、叶黄素酯或其任意混合物。该所述混合物，指前述各组分中任意2中或2中以上的组分，按照任意比例的混合物。
在上述技术方案基础之上，具体的实施方式中，所述的原料混合物中还含有抗氧化剂，所述的抗氧化剂选自生育酚，脂肪酸抗坏血酸酯，丁基羟基甲苯(BHT)，丁基羟基茴香醚(BHA)，丙基没食子酸，叔丁基羟基喹啉或其任意混合物；所述的抗氧化剂质量为微粒质量的0.1-10％；优选1-5％。
再一方面，本发明中队纳米乳液粒径的限定基于必要的试验结果，根据本发明所记载的实施例，粒径控制严格的技术方案中(实施例2和5)，所获得的微粒产物具有显著优异的含量及稳定性。
本发明的叶黄素/叶黄素酯微粒可作为一种原料，进一步加工成片剂、胶囊形式的膳食补充剂，或制成固体饮料、能量棒或糖果形式的食品及功能食品。
下述非限制性实施例用于进一步阐明本发明的技术方案及效果，但不应当理解为对本发明任意形式的限定。
如无特殊说明，本申请中采用下述方法对产品进行测量和评价。
本发明中，采用表面色素含量表征微囊化效率，表面色素含量越高，微囊化效率越低，未包埋的叶黄素/叶黄素酯越多，同时稳定性越差。本发明所述的表面色素含量的测定方法为：5g待测微囊产品加入茄形瓶，向其中加入20ml石油醚(30-60℃)，转摇20s后过滤，重复洗涤两次，合并滤液，旋蒸脱除石油醚，105℃烘干至恒重。剩余固体干重与待测微囊产品的质量比即为表面色素含量，以百分比表示。
本发明所述产品加速稳定性评价方法为中国药典提供的方法：40℃，75％RH条件下，测定的不同时间的色素含量以确定其稳定性优劣。色素保留率为不同时间时产品含量和初始含量的比率。同时提供一种快速评价产品稳定性的方法：60℃，抽真空或充氮气条件下测定20天的稳定性，同样以色素保留率来表示产品稳定性。
本发明所述的乳液粒径由激光粒度仪测定，并记录D99/D90/D50的数值，以μm为单位。
实施例1
在200ml水中加入叶黄素酯晶体170g，抗坏血酸棕榈酸酯20g，抗坏血酸钠30g，维生素E30g，15℃下高速分散1h；常温下将羟丙甲基纤维素100g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的叶黄素酯水溶液中，保持乳液温度为25℃，搅拌30min；经过胶体磨高速分散得到叶黄素酯乳液，乳液粒径为D99/D90/D50＝57.21/47.65/27.52μm，将该乳液以喷涂的形式喷涂在680g、150-200微米的蔗糖-淀粉颗粒表面。叶黄素酯乳液层层包裹后蔗糖-淀粉颗粒后，形成的叶黄素酯微粒A(理论含量为12.2％)，含量12.1％，表面色素含量9.8％，堆密度0.60g/ml。其60℃，真空或充氮条件下，20天的色素保留率77％；其40℃，75％RH条件下的6个月的色素保留率为82％。从该结果可见，未使用助剂的情况下，产品粒径57.21微米，所得产品稳定性差。
实施例2
将普鲁兰多糖16.7g溶于200ml水中，加入叶黄素晶体90g，抗坏血酸棕榈酸酯20g，抗坏血酸硬脂酸酯30g，dl-α-生育酚30g，25℃下高速分散1h；常温下将羟丙甲基纤维素133.3g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的叶黄素水水溶液中，保持乳液温度为25℃，搅拌30min；经过胶体磨高速分散得到叶黄素乳液，乳液粒径为D99/D90/D50＝0.90/0.75/0.21μm，将该乳液以喷涂的形式喷涂在680g、180-300微米的淀粉-糖颗粒表面。叶黄素乳液层层包裹后蔗糖淀粉颗粒后，形成叶黄素微粒B(理论含量为6.3％)，含量6.4％，表面色素含量0.1％，堆密度0.75g/ml。其60℃，真空或充氮条件下，20天的色素保留率98％；其40℃，75％RH条件下的6个月的色素保留率为99.7％。
在本实施例中，添加了普鲁兰多糖作为助乳化剂，羟丙甲基纤维素和普鲁兰多糖总量占颗粒质量的15％，二者的比例为8:1。所得乳液粒径1微米以下，所得叶黄素产品色素保留率高，20天保留率98％。与实施例1相比，可见普鲁兰多糖的添加对粒径和稳定性的影响较大。
实施例3
将葡聚糖8.6g溶于200ml水中，加入玉米黄质晶体170g，BHT 20g，抗坏血酸钠30g，维生素E30g，35℃下高速分散1h；常温下将甲基纤维素172g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的玉米黄质水溶液中，保持乳液温度为30-35℃，搅拌30min；经过胶体磨高速分散得到玉米黄质乳液，乳液粒径为D99/D90/D50＝86.05/57.95/34.23μm，将该乳液以喷涂的形式喷涂在572.8g蔗糖-淀粉颗粒表面。玉米黄质乳液层层包裹后蔗糖-淀粉颗粒后，形成玉米黄质微粒C(理论含量为10.2％)，含量为10.2％，表面色素含量为8.8％，堆密度0.55g/ml。其60℃，真空或充氮条件下，20天的色素保留率80％；其40℃，75％RH条件下的6个月的色素保留率为81％。与实施例2的实验结果对比可见：葡聚糖，甲基纤维素的组合用于本发明所获得的微囊产品，相较实施例2条件下所获得产品在粒径和稳定性两方面都更差一些。
实施例4
将黄原胶12.5g溶于200ml水中，加入玉米黄质晶体35g，叶黄素晶体150g，抗坏血酸棕榈酸酯20g，BHA 30g，维生素E30g，35℃下高速分散1h；常温下将羧甲基纤维素钠187.5g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的玉米黄质质-叶黄素水溶液中，保持乳液温度为30-35℃，搅拌30min；经过胶体磨高速分散得到玉米黄质-叶黄素乳液，乳液粒径为D99/D90/D50＝105.21/87.34/45.38μm，将该乳液以喷涂的形式喷涂在675g、150-250微米的蔗糖-淀粉颗粒表面。玉米黄质-叶黄素乳液层层包裹后蔗糖-淀粉颗粒后，形成玉米黄质-叶黄素微粒D(理论含量为叶黄素10.5％，玉米黄质2.1％)，叶黄素含量为10.4％，玉米黄质含量2.2％，表面色素含量为11.7％，堆密度0.65g/ml。其60℃，真空或充氮条件下，20天的色素保留率74％；其40℃，75％RH条件下的6个月的色素保留率为76％。与实施例2的实验结果对比可见：黄原胶和羧甲基纤维素钠的组合用于本发明所获得的微囊产品，相较实施例2条件下所获得产品在粒径和稳定性两方面都更差一些。
实施例5
将普鲁兰多糖121.4g溶于200ml水中，加入叶黄素酯晶体3570g，35℃下高速分散1h；常温下将羟丙甲纤维素1578.2g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的叶黄素酯水溶液中，保持乳液温度为30℃，搅拌30min；经过胶体磨高速分散得到叶黄素酯乳液，乳液粒径为D99/D90/D50＝0.92/0.47/0.23μm，将该乳液以喷涂的形式喷涂在4730.4g、300-425微米的蔗糖-淀粉颗粒表面。叶黄素酯乳液层层包裹后蔗糖-淀粉颗粒后，分别于喷涂12h、20h、24h时取样，得到叶黄素酯产品E、F、G(理论含量分别为12.1％、21.0％、25.0)。含量分别为11.9％、20.2％、25.1％，表面色素含量分别为0.25％、0.27％、0.31％，堆密度分别为0.75g/ml、0.78g/ml、0.77g/ml。其60℃，真空或充氮条件下，20天的色素保留率分别为99.8％、100.2％、99.3％；其40℃，75％RH条件下的6个月的色素保留率为98.2％、99.6％、97.5％。
实施例6
将黄原胶21.7g溶于200ml水中，加入叶黄素酯晶体170g，抗坏血酸硬脂酸酯20g，抗坏血酸钠30g，维生素E30g，25℃下高速分散1h；常温下将羟丙甲纤维素108.5g配置成6.25％的水溶液，搅拌溶解后，倾倒入高速分散的叶黄素酯水溶液中，保持乳液温度为35℃，搅拌30min；经过胶体磨高速分散得到叶黄素酯乳液，乳液粒径为D99/D90/D50＝65.21/34.34/23.38μm，将该乳液以喷涂的形式喷涂在150-425微米的619.8g蔗糖-淀粉颗粒表面。叶黄素酯乳液层层包裹后蔗糖-淀粉颗粒后，形成叶黄素酯微粒H(理论含量为叶黄素酯12.2％)，叶黄素酯含量为12.4％，表面色素含量为9.7％，堆密度0.55g/ml。其60℃，真空或充氮条件下，20天的色素保留率82％；其40℃，75％RH条件下的6个月的色素保留率为79％。
实施例7
将100g叶黄素酯晶体溶于300g橄榄油中，加热至60-90℃溶解晶体，晶体熔融后加入到520g阿拉伯胶水溶液中，搅拌分散后，加入抗坏血酸棕榈酸酯20g，丙基没食子酸30g，维生素E30g，以喷雾干燥工艺制备叶黄素酯微粒，得到叶黄素酯微粒I，含量为6.5％(理论含量8.0％)，表面色素含量为7.7％，堆密度0.35g/ml。其60℃，真空或充氮条件下，20天的色素保留率50％；其40℃，75％RH条件下的6个月的色素保留率为56％。
本实施例的处理方法代表了本领域现有技术中处理的一般方法，即采用加热熔融的方法处理物料。与实施例2的技术方案及效果相比可见：加热熔融过程中活性物质含量就有损失，同时得到产品后产品稳定性也很差，与本发明的方案存在实质差异。
实施例8：叶黄素/叶黄素酯产品打片稳定性
将实施例1-6中的叶黄素/叶黄素酯微粒，和多种维生素打片辅料混料后，添加量为10mg/片，使用天峰ZPW-8型旋转式压片机进行压片，得到复合类叶黄素/叶黄素酯维生素片，片剂硬度80-100N，脆碎度≤0.1％，将片剂包装在其盖用热封铝箔密封的HDPE瓶中，在40℃和75％的相对湿度下将片剂储存6个月，不同时间色素含量保留率见表1。
从表1的数据可以看出以普鲁兰多糖和羟丙甲纤维素组合使用的微粒B和G在产品应用方面具有较好特性，产品稳定性高。其他形式的产品稳定性较B和G差。
表1
Claims (10)
1.叶黄素/叶黄素酯微粒，通过将含有叶黄素和/或叶黄素酯、壁材以及助乳化剂的原料混合物在低温条件下制备成粒径不超过1微米的纳米乳液，再喷涂至蔗糖-淀粉颗粒上制备；所述的壁材是纤维素衍生物。
2.根据权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的壁材是羟丙甲纤维素、甲基纤维素、乙基纤维素、羧甲基纤维素钠中的一种或几种的混合物。
3.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的壁材是羟丙甲纤维素。
4.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的助乳化剂是是黄原胶、普鲁兰多糖或二者的混合物。
5.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的助乳化剂为普鲁兰多糖。
6.权利要求1所述的叶黄素/叶黄素酯，其特征在于，所述的壁材和助乳化剂的质量比为5-20:1。
7.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的壁材与助乳化剂的用量总和为微粒质量的10-20％。
8.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的叶黄素/叶黄素酯为万寿菊来源的叶黄素、玉米黄质、叶黄素酯或其任意混合物。
9.权利要求1所述的叶黄素/叶黄素酯微粒，其特征在于，所述的原料混合物中还含有抗氧化剂，所述的抗氧化剂选自生育酚，脂肪酸抗坏血酸酯，丁基羟基甲苯，丁基羟基茴香醚，丙基没食子酸，叔丁基羟基喹啉或其任意混合物；所述的抗氧化剂质量为微粒质量的0.1-10％。
10.权利要求1所述的叶黄素/叶黄素酯微粒的制备方法，包括下述步骤：
(1)将原料混合物在10-35℃条件下制备成粒径不超过1微米的纳米乳液；
所述的原料混合物含有叶黄素和/或叶黄素酯、壁材以及助乳化剂；
所述的壁材是纤维素衍生物；
(2)将步骤(1)制得的纳米乳液喷涂至蔗糖-淀粉颗粒上。
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