CN1764439A - 制备交联明胶珠粒的方法 - Google Patents
制备交联明胶珠粒的方法 Download PDFInfo
- Publication number
- CN1764439A CN1764439A CNA2004800082561A CN200480008256A CN1764439A CN 1764439 A CN1764439 A CN 1764439A CN A2004800082561 A CNA2004800082561 A CN A2004800082561A CN 200480008256 A CN200480008256 A CN 200480008256A CN 1764439 A CN1764439 A CN 1764439A
- Authority
- CN
- China
- Prior art keywords
- vitamin
- beadlet
- scope
- active component
- carotenoid
- Prior art date
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- Granted
Links
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Abstract
本发明提供了制备一种含有一种或多种活性成分的交联珠粒的方法,所述活性成分选自脂溶性维生素活性物质、类胡萝卜素或多不饱和脂肪酸,所述方法包括:在90℃至140℃的温度下,将干微粒处理30秒至30分钟,或1分钟至10分钟,或3分钟至7分钟。
Description
技术领域
本发明涉及制备具有高浓度活性成分的珠粒的方法、所得的珠粒和含有它们的组合物,所述活性成分选自脂溶性维生素、类胡萝卜素和多不饱和脂肪酸。
发明内容
更具体地,本发明提供了一种制备含有一种或多种活性成分的交联珠粒的方法,所述活性成分选自脂溶性维生素活性物质、类胡萝卜素或多不饱和脂肪酸,所述方法包括:在90℃至140℃的温度下,对干微粒进行30秒至30分钟,或1分钟至10分钟,或3分钟至7分钟的处理。
发明详述
脂溶性维生素活性物质的例子包括含维生素的油、天然以及合成的前维生素和纯的或基本上纯的维生素、或其化学衍生物以及它们的混合物。选自维生素A、D、E和K或其衍生物的维生素特别受关注。例如,术语“维生素E”包括合成制得的生育酚或天然生育酚的混合物。维生素衍生物的例子包括维生素A乙酸酯、维生素A棕榈酸酯和维生素E乙酸酯。维生素D活性物质的例子是维生素D3。作为具体例子,本发明的方法可得到含有维生素A活性物质和维生素D活性物质,例如维生素A和维生素D3的珠粒。
在一种实施方式中,本发明的方法可以包括维生素A作为脂溶性维生素活性物质,其总浓度在500,000IU维生素A/g珠粒至1,500,000IU维生素A/g珠粒的范围内,在750,000IU维生素A/g珠粒至1,500,000IU维生素A/g珠粒的范围内,或在750,000IU维生素A/g珠粒至1,300,000IU维生素A/g珠粒的范围内,例如,维生素A可以以500,000±35,000IU活性成分/g珠粒、750,000±35,000IU活性成分/g珠粒、1,000,000±35,000IU活性成分/g珠粒、或1,100,000±35,000IU活性成分/g珠粒的总浓度存在于珠粒中。作为脂溶性维生素活性物质的维生素D可以以100,000IU维生素D/g珠粒至500,000IU维生素D/g珠粒的范围,或100,000IU维生素D/g珠粒至200,000IU维生素D/g珠粒的范围存在,作为脂溶性维生素活性物质的维生素E可以以50%至75%维生素E的范围存在。
类胡萝卜素的例子包括β-胡萝卜素、番茄红素、玉米黄质(zeaxanthin)、虾青素、叶黄素、辣椒红和隐黄素(cryptoxanthin)。
在一种实施方式中,本发明的方法可以包括总浓度在5%至20%范围内、5%至15%范围内或7%至15%范围内的类胡萝卜素。
作为甘油三酸酯和/或乙酯形式存在的多不饱和脂肪酸的例子,包括花生四烯酸、二十碳五烯酸、二十二碳六烯酸和γ-亚麻酸和/或乙酯。
在一种实施方式中,本发明的方法可以包括总浓度在20%至50%范围内、25%至40%范围内或28%至38%范围内的作为甘油三酸酯存在的多不饱和脂肪酸。
本发明的方法中所用的干微粒形式可以通过技术人员已知的任何工序来制备,例如通过形成含有活性成分、乳化剂、结构改性剂(texturingagent)和还原糖的水性乳液,然后将该乳液转化为含有所述乳液的非水性组分的干微粒。
乳化剂的例子是明胶和棕榈酸抗坏血酯(ascorbyl palmitate)。明胶是同时充当结构改性剂的乳化剂。任何“勃氏强度(bloom)”在约0至约300的明胶都可用于本发明的实施中。可以使用A型和B型明胶。优选使用的明胶是Bloom 140,但是明胶Bloom 30或Bloom 75也可以使用。在明胶的存在下,其它的结构改性剂可以不是必需的。
乳化剂的浓度取决于所用乳化剂的种类,例如明胶的浓度可以在25%至35%或更少的范围内。
除明胶之外的结构改性剂的例子包括角叉菜聚糖、改性淀粉、改性纤维素、黄原胶、阿拉伯树胶、果胶、瓜尔豆胶、角豆(caroub)胶、麦芽糖糊精和藻酸盐。
结构改性剂的浓度取决于所用结构改性剂的种类,例如可以在0%至15%的范围内。
还原糖的例子是果糖、葡萄糖、乳糖、麦芽糖、木糖、阿拉伯糖、核糖和蔗糖。可以使用一种类型的糖,或者两种或更多种糖的混合物。还原糖可以直接添加,或者以糖浆形式添加,例如果糖或葡萄糖糖浆。
还原糖的浓度取决于所用还原糖的种类,例如可以在2%至10%的范围内,或者明胶∶糖的比在3∶1至7∶1之间,例如5∶1。
也可以包括少量的其它成分,包括抗氧化剂,例如6-乙氧基-1,2-二羟基-2,2,4-三甲基喹啉(乙氧基喹啉)、3,5-二叔丁基-4-羟基甲苯(BHT)和3-叔丁基-羟基苯甲醚(BHA);保湿剂,例如甘油、山梨糖醇、聚乙二醇、丙二醇;增补剂(extender)和增溶剂。
作为典型的例子,可以将明胶和合适的糖溶于已混有甘油的水中。溶解过程可以在65-70℃持续例如大约30分钟。然后,例如可以加入维生素A和抗氧化剂,并进行乳化。例如基于转子/定子原理,可以通过胶体磨完成预乳化。预乳化可以在500至1500rpm的转子旋转速度下进行15至30分钟,然后可以通过高压均质机,使乳液转化为细液滴。
在一个实施例中,乳液滴向“成型(set up)”颗粒的转化可以通过下述方法来达到:将乳液滴喷雾到精细分散粉末颗粒在空气中的搅动云状物或悬浮物中,例如使乳液通过旋转喷头进入粉末物质在空气中的悬浮物内,该悬浮物包含在旋转式圆柱转筒中,并被搅拌,转筒和喷头的旋转方向相反,使得粉末在空气中的云状物或悬浮物相对于进入的乳液喷雾反向漩动。
该方法中所用的用于收集/包覆乳液滴的精细分散粉末的例子包括多糖,例如淀粉和改性淀粉;单独的硅酸钙,或者硅酸钙与下述混合物组分的其中之一的混合物:微晶纤维素、硅酸镁、氧化镁、硬脂酸、硬脂酸钙、硬脂酸镁、亲水硅酸和高岭土。仅由硅酸钙组成的包覆物是优选的。硅酸钙可以全部或部分地以水合物的形式存在。
特别合适的硅酸钙颗粒具有如下特点:大小小于0.2μm,尤其小于0.1μm;比表面至少大约80m2/g至大约180m2/g,优选大约95m2/g至120m2/g;团聚为平均尺寸大约5-30μm,优选为5-20μm的团聚体。SiO2/CaO的比在1.65至2.65之间。
在仅由硅酸钙组成的包覆物中,硅酸钙的含量可以在2wt.%至12wt.%的范围内,优选在4wt.%至9wt.%的范围内。
在由硅酸钙和一种或多种上述混合物组分的混合物组成的包覆物中,硅酸钙混合物的量可以在5wt.%至25wt.%的范围内。
可选地,得到的干微粒可以与残余的精细分散粉末分离。这可以通过本身常规的操作来完成,例如简单地将粉末和干微粒的混合物进料至选定尺寸的振动筛中,以留下干微粒,而使收集粉末通过。
为进一步加工,这些含有活性物质的干微粒优选具有小于10%,优选大约4至6%的水含量。如果水含量更高,可以通过各种方法将干微粒干燥至期待的水含量,例如通过将其在室温下暴露于空气中,或者通过在37℃至45℃的干燥炉中将其适当加热。
热处理例如可以在间歇或连续的工艺过程中进行,在工艺过程中控制珠粒停留时间和温度。
在流化床工艺的情况下,可以将珠粒在间歇工艺的一开始,或者在连续流化床工艺中持续地加入至温度在100至200℃之间,优选在130-160℃的热空气或氮气流中。珠粒温度在几秒至一分钟内升高到100℃以上,使得迅速高效地反应。5至10分钟后珠粒就处理好了。处理结束时,对珠粒进行冷却。
在连续快速处理的情况下,珠粒被连续进料至温度在100至200℃之间,优选在130-160℃的热气流中。可以通过机械搅拌,例如在300rpm以上来使珠粒运动。也可以将用于进行此热处理的容器壁加热至110至180℃的温度。所期待的珠粒交联可在30秒至10分钟,或者在1分钟至10分钟内完成,最高珠粒温度在90至140℃的范围内,优选在105至125℃。
由本发明方法获得的珠粒形式具有核和表面区域,其中减少了活性成分在表面区域的损失,这也是本发明的一个目的。
因此,本发明还提供了一种具有核和表面区域的珠粒形式,其中核区域含有高浓度的一种或多种选自脂溶性维生素活性物质、类胡萝卜素或多不饱和脂肪酸的活性成份;表面区域含有小于10%总含量的活性成分,优选小于5%总含量的活性成分。
在一种实施方式中,本发明提供了一种含有一种或多种选自下述活性成分的珠粒:维生素A,总浓度在800,000IU维生素A/g珠粒至1,500,000IU维生素A/g珠粒的范围内,或在950,000IU维生素A/g珠粒至1,250,000IU维生素A/g珠粒的范围内;维生素D,总浓度在100,000IU维生素D/g珠粒至500,000IU维生素D/g珠粒的范围内,或100,000IU维生素D/g珠粒至200,000IU维生素D/g珠粒的范围内;维生素E,总浓度在50%至75%的范围内;类胡萝卜素,总浓度在5至20%的范围内;以及多不饱和脂肪酸,总浓度在5至50%的范围内,其中表面区域含有小于10%总含量的活性成分。在另一种实施方式中,表面区域含有小于5%总含量的活性成分。
珠粒的特征在于高稳定性和势能(potency)。在它们被制粒时,呈现出高稳定性,例如它们经得住进料制粒过程的温度、水分以及压力,而不会损失其物理完整性。它们不溶于水,在涉及生物可获得性时保持了其性质。
本发明珠粒的典型例子例如可以具有如下组分:30%至45%的维生素A、0%至2%的维生素D3、5%至15%的6-乙氧基-1,2-二羟基-2,2,4-三甲基喹啉(EMQ)、25%至35%的明胶、5%至10%的果糖、2%至10%的甘油、5%至10%的硅酸钙、0%至25%的玉米淀粉、0%至1%的可食用脂肪和水。
实施例1制备含有1,000,000IU维生素A/g珠粒和200,000IU维生素D3/g珠粒的珠粒
在65℃下,通过加热将大约90份的明胶Bloom 140和18份果糖溶于313.2份水(含有23.2份甘油)中。然后将得到的基质与158份含有24%乙氧基喹啉的维生素A(分析结果是每克2.1Mio.IU维生素A)和3.5份维生素D3(分析结果是每克20Mio.IU维生素D3)混合,接着进行预乳化。
使用硅酸钙作为精细分散粉末,将珠粒喷雾出。珠粒的平均颗粒大小在200μm至300μm。
将该珠粒分为两组:对其中一组,使用传统加热缓慢混合器进行处理,该混合器对珠粒的热过程没有足够控制;对另一组,通过流化床进行处理,即采用其中可以控制珠粒的温度和停留时间的装置进行的间歇工艺。下表中对结果进行了比较:
加热缓慢混合器 | 流化床 | |
交联后的维生素A含量(IU/g) | 1,025,000 | 1,050,000 |
维生素A损失(%) | 3-4 | 0-1 |
表面维生素A(%) | 8-10 | 1-2 |
交联级别(%) | 76% | 82% |
在流化床中,将温度控制于100至115℃之间5分钟。在加热缓慢混合器中,在温度从90℃升至124℃下,将珠粒加热大约15分钟。
实施例2制备含有1,000,000IU维生素A/g珠粒的珠粒
在65℃下,通过加热将大约100份的明胶Bloom 140和20份果糖溶于308.2份水(含有13.2份甘油)中。然后将得到的基质与170份含有24%乙氧基喹啉的维生素A(分析结果是每克2.1Mio.IU维生素A)混合,接着进行预乳化。
使用硅酸钙作为精细分散粉末,将珠粒喷雾出。珠粒的平均颗粒大小在180μm至270μm。
将该珠粒分为三组:如实施例1,使用传统加热缓慢混合器处理第一组,如实施例1使用流化床处理第二组,通过在稀释相中的连续快速处理来处理第三组,其中该快速处理是由气力输送和机械输送的组合来确保的。下表中对结果进行了比较:
加热缓慢混合器 | 流化床 | 快速处理 | |
交联后的维生素A含量(IU/g) | 1,119,000 | 1,146,000 | 1,143,000 |
维生素A损失(%) | 3-4 | 0-1 | 0-1 |
表面维生素A(%) | 8-10 | 2-2.5 | 3-5 |
交联级别(%) | 50-80 | 50-80 | 50-80 |
在流化床中,将温度控制于110至120℃之间5分钟。在快速处理中,在温度从115℃升至125℃下,处理珠粒1至4分钟。在加热缓慢混合器中,将珠粒加热大约20分钟,温度从70℃升至124℃。
实施例3含有高浓度维生素A的珠粒的稳定性
在将实施例1和实施例2的交联珠粒在40℃和75%的rH下贮存4周后,就保持时间而言的典型稳定性表现是大约90-95%,这与含有500,000IU维生素A/g活性成分的标准交联维生素A形式相当。
实施例4制备含有1,000,000IU维生素A/g珠粒的珠粒
在65℃下,通过加热将大约100份的明胶Bloom 140和20份果糖溶于308.2份水(含有13.2份甘油)中。然后将得到的基质与170份含有24%乙氧基喹啉的维生素A(分析结果是每克2.1Mio.IU维生素A)混合,接着进行预乳化。
使用硅酸钙作为精细分散粉末,将珠粒喷雾出。珠粒的平均颗粒大小在200μm至300μm。
通过在稀释相中的连续快速处理来对处理3堆珠粒,其中快速处理是由气力输送和机械输送的组合来确保的。下表中对结果进行了比较:
第一堆 | 第二堆 | 第三堆 | |
交联后的维生素A含量(IU/g) | 1,064,808 | 1,051,641 | 1,077,224 |
维生素A损失(%) | <1 | <1 | <1 |
表面维生素A(%) | 3.7 | 4.0 | 3.5 |
交联级别(%) | 60-85 | 60-85 | 60-85 |
在快速处理中,在温度从105℃升至115℃下,将珠粒处理1至5分钟。
实施例5含有高浓度维生素A的珠粒的稳定性
在将实施例4的交联珠粒于40℃和75%的rH下贮存4周之后,就保持时间而言的典型稳定性表现是大约95-100%,这与含有500,000IU维生素A/g活性成分的标准交联维生素A形式相当。
实施例6制备含有1,000,000IU维生素A/g珠粒和200,000IU维生素D3/g珠粒的珠粒
在65℃下,通过加热将大约90份的明胶Bloom 140和18份果糖溶于313.2份水(含有23.2份甘油)中。然后将得到的基质与158份含有24%乙氧基喹啉的维生素A(分析结果是每克2.1Mio.IU维生素A)和3.5份维生素D3(分析结果是每克20Mio.IU维生素D3)混合,接着进行预乳化。
使用硅酸钙作为精细分散粉末,将珠粒喷雾出。珠粒的平均颗粒大小在200μm至300μm。
通过在稀释相中的连续快速处理来处理3堆珠粒,其中快速处理是由气力输送和机械输送的组合来确保的。下表中对结果进行了比较:
第一堆 | 第二堆 | 第三堆 | |
交联后的维生素A含量(IU/g) | 1,105,039 | 1,074,633 | 1,077,470 |
交联后的维生素D3含量(IU/g) | 218,617 | 214,813 | 217,858 |
维生素A损失(%) | <1 | <1 | <1 |
表面维生素A(%) | 4.7 | 4.7 | 4.6 |
交联级别(%) | 60-85 | 60-85 | 60-85 |
在快速处理中,在温度从105℃升至115℃下,将珠粒处理1至5分钟,。
实施例7含有高浓度维生素A和D3的珠粒的稳定性
在将实施例6的交联珠粒于40℃和75%的rH下贮存4周之后,就保持时间而言的典型稳定性表现分别为维生素A是大约95-100%,D3是大约100%,这与含有500,000IU维生素A/g和100,000IU维生素D3/g活性成分的标准交联维生素AD3形式相当。
Claims (11)
1.一种制备含有一种或多种活性成分的交联珠粒的方法,所述活性成分选自脂溶性维生素活性物质、类胡萝卜素或多不饱和脂肪酸,所述方法包括:在90℃至140℃的温度下,将干微粒处理30秒至30分钟,或1分钟至10分钟,或3分钟至7分钟。
2.如权利要求1所述的方法,其中所述脂溶性维生素活性物质选自维生素A、维生素D和维生素E,所述类胡萝卜素选自β-胡萝卜素、番茄红素、玉米黄质、虾青素、叶黄素、辣椒红和隐黄素,所述多不饱和脂肪酸选自花生四烯酸、二十碳五烯酸、二十二碳六烯酸和γ-亚麻酸及其甘油三酸酯和乙酯。
3.如权利要求2所述的方法,其中所述脂溶性维生素活性物质、类胡萝卜素和多不饱和脂肪酸的浓度选自:在500,000IU维生素A/g珠粒至1,500,000IU维生素A/g珠粒的范围内,在100,000IU维生素D/g珠粒至500,000IU维生素D/g珠粒的范围内,在50%至75%维生素E的范围内,在5%至20%类胡萝卜素的范围内和在20%至50%作为甘油三酸酯存在的多不饱和脂肪酸的范围内的总浓度。
4.如权利要求1所述的方法,其中干微粒的水分含量小于10%。
5.如权利要求1所述的方法,其中热处理是在其中控制珠粒停留时间和温度的间歇或连续工艺中获得的。
6.如权利要求1所述的方法,其中所述珠粒被加入到温度在100至200℃的热空气或氮气流中。
7.如权利要求1所述的方法,其中在加入干微粒之后,温度在几秒至1分钟的时间内升高到100℃以上。
8.如权利要求1所述的方法,其中加热发生在最高珠粒温度在110℃至140℃下。
9.一种具有核和表面区域的交联珠粒形式,其中所述核区域含有高浓度的一种或多种选自脂溶性维生素活性物质、类胡萝卜素或多不饱和脂肪酸的活性成分;所述表面区域含有小于10%或小于5%总含量的活性成分。
10.一种含有一种或多种活性成分的交联珠粒形式,所述活性成份选自:维生素A,总浓度在800,000IU维生素A/g珠粒至1,500,000IU维生素A/g珠粒的范围内;维生素D,总浓度在100,000IU维生素D/g珠粒至500,000IU维生素D/g珠粒的范围内;维生素E,总浓度在50%至75%的范围内;类胡萝卜素,总浓度在5至20%的范围内;以及多不饱和脂肪酸,总浓度在5至50%的范围内,其中表面区域含有小于10%或小于5%总含量的活性成分。
11.如权利要求10所述的交联珠粒形式,具有如下组分:30%至45%的维生素A、0%至2%的维生素D3、5%至15%的6-乙氧基-1,2-二羟基-2,2,4-三甲基喹啉、25%至35%的明胶、5%至10%的果糖、2%至10%的甘油、5%至10%的硅酸钙、0%至25%的玉米淀粉、0%至1%的可食用脂肪和水。
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CN105072926A (zh) * | 2013-03-28 | 2015-11-18 | 帝斯曼知识产权资产管理有限公司 | 适合婴幼儿食品制剂的叶黄素组合物 |
CN110250521A (zh) * | 2019-05-15 | 2019-09-20 | 万华化学集团股份有限公司 | 一种维生素a乙酸酯微胶囊的制备方法 |
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WO2017144435A1 (en) * | 2016-02-26 | 2017-08-31 | Dsm Ip Assets B.V. | Novel coating system (ii) |
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CN105072926A (zh) * | 2013-03-28 | 2015-11-18 | 帝斯曼知识产权资产管理有限公司 | 适合婴幼儿食品制剂的叶黄素组合物 |
CN103719301A (zh) * | 2013-12-24 | 2014-04-16 | 青岛银色世纪健康产业集团有限公司 | 以虾青素油为主料的健康食品 |
CN110250521A (zh) * | 2019-05-15 | 2019-09-20 | 万华化学集团股份有限公司 | 一种维生素a乙酸酯微胶囊的制备方法 |
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EP1605917A1 (en) | 2005-12-21 |
KR101143708B1 (ko) | 2012-05-09 |
KR20060002870A (ko) | 2006-01-09 |
US20060057214A1 (en) | 2006-03-16 |
CN1764439B (zh) | 2010-05-26 |
ES2542687T3 (es) | 2015-08-10 |
US8211471B2 (en) | 2012-07-03 |
WO2004084862A1 (en) | 2004-10-07 |
EP1605917B1 (en) | 2015-04-22 |
JP2006521312A (ja) | 2006-09-21 |
US20090214661A1 (en) | 2009-08-27 |
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