CN1516578A - 制备分散体的方法 - Google Patents

制备分散体的方法 Download PDF

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CN1516578A
CN1516578A CNA028121899A CN02812189A CN1516578A CN 1516578 A CN1516578 A CN 1516578A CN A028121899 A CNA028121899 A CN A028121899A CN 02812189 A CN02812189 A CN 02812189A CN 1516578 A CN1516578 A CN 1516578A
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Abstract

本发明涉及一种制备活性物质或组合物在水相中的分散体的方法，其包括将这种活性物质或组合物在二甲醚或C4烃或其混合物中的溶液以其超临界或近临界状态分散在水相中、使混合物减压并从气态溶剂中分离出分散体。

Description

制备分散体的方法
本发明涉及一种制备水分散体的方法。更确切地说，本发明涉及一种制备活性物质或组合物在水相中的分散体的方法。按照本发明，制备活性物质或组合物的水分散体的方法包括将这种活性物质或组合物在二甲醚或C4烃或其混合物中的溶液以其超临界或近临界状态分散在水相中、使混合物减压并从气态溶剂中分离出分散体。
这里使用的术语“分散体”包括乳液和悬浮液，并涉及其中分散颗粒处于微米或纳米尺寸范围内且优选平均粒径为大约50nm至大约300nm的体系。术语“活性物质或组合物”表示符合以下几个特点的任何物质或组合物，即可以溶于二甲醚或C4烃类且基本上不溶于水、在环境条件下可以是固体或液体并且通常具有生理活性。这种活性物质的实例特别是脂溶性维生素A、D、E、K；和类胡萝卜素如β-胡萝卜素、角黄素、阿朴胡萝卜素醛(apocarotenal)、虾青素、阿朴酯(apoester)、叶黄素、番茄红素、玉米黄质、柑桔皮类胡萝卜素(citranaxanthin)、圆酵母红素；脂溶性药物；其他脂溶性(卫生保健)成分如PUFA(多不饱和脂肪酸)、姜黄素、辅酶Q10、α-硫辛酸。
C4烃类的实例是带有4个碳原子的烃类，其可以是饱和的C4烃类如正丁烷和异丁烷，或不饱和的C4烃类如1-丁烯、反式丁烯和异丁烯。这些物质中特别优选反式丁烯、1-丁烯和二甲醚，尤其是1-丁烯用于制备β-胡萝卜素水分散体。
本发明的方法适宜按照下述过程进行，即将水相和处于超临界或近临界状态的活性物质或组合物在适当溶剂中的溶液分别供入混合室，并使混合物减压。示意地，本发明的方法可以如图1所示进行。在高压釜 1中将活性物质或组合物分散在合适的加压溶剂如二甲醚中。高压釜 1中的溶剂压力应当高于饱和蒸汽压。所得的分散体借助高压泵 2(例如Lewa TypEL-3隔膜泵；供应商：HERBERT OTT AG，Missionsstrasse 22，CH-4003巴塞尔)经换热器(例如，套管换热器) 3在温度和压力接近或超过溶剂临界常数的条件下(即溶剂达到超临界或近临界状态)供入混合室 4。例如，压力为大约45巴至大约2000巴，适宜地大约45巴至300巴，且优选大约80巴至大约200巴。将第二高压釜 5中的可能含有额外试剂如稳定剂或表面活性剂的水相经过高压泵 6(例如，LABOMATIC HD-300活塞泵；供应商：LABOMATIC Instruments AG，Ringstr.13，CH-4123 Allschwil)和换热器7(例如，套管换热器)在大体上对应泵 2和 6产生的压力以及足以保持混合室 4处于超临界或近临界条件的温度下供入混合室 4。在混合室4中，各相混合并经孔 8减压，然后通过停留区 9，由此产生了精细分散的不含溶剂的水悬浮液或水乳液。
泵 2和 6可以是任何通常在高压技术中使用的泵例如隔膜泵或活塞泵。换热器 3和 7可以是常规换热器例如管状换热器或套管换热器。适当地设计高压釜 1和 5(例如，METIMEX Typ HPM，供应商：PREMEXREACTOR AG，Industriestrasse 11，Postfach 444)，允许其对内容物预热。混合室 4包括至少一个水相进口、至少一个非水相(溶剂相)进口和一个包含膨胀孔的出口。水相和溶剂相的进口可以以0-180度的角度设置，即两者相互平行或两者相对，或经设置后使两股流体以0度和180度以外的角度，例如大约30度至90度的角度交汇。混合室宜为管状并且其尺寸可以确保湍流条件，即尺寸足够小。
孔 8宜为圆形，并且其直径宜为大约0.05mm至大约1.0mm，优选大约0.1mm至0.4mm。通过孔 8将使分散体膨胀。该膨胀作用将使加压溶剂蒸发且同时使颗粒沉淀。经过管中的停留时间后，可以容易地将最终分散体从气态溶剂中分离。
图2显示了由混合室 4和膨胀孔 8组成的示例性膨胀单元。通过在混合室中混合溶剂相 10和水相 11，得到了预制乳液(即，其中颗粒尺寸大于最终需要的尺寸的乳液)。通过孔8将使乳液膨胀。该膨胀作用将使加压溶剂蒸发且同时使颗粒沉淀。经过停留区9中的停留时间后，最终分散体离开( 12)该单元并可以容易地将其从气态溶剂中分离出来。
温度和压力必须根据本发明方法中使用的特殊溶剂进行调节，从而确保体系达到超临界状态，这一点是容易理解的。因此，当使用二甲醚(临界常数Tk=126.9℃、pk＝53.7巴)时，原料流进入混合室的温度应当至少为80℃。当使用二甲醚时，温度优选调节为80-160℃。含有活性物质的溶液在换热器中的停留时间并不十分关键，且通常在秒范围内。混合物溶液在混合室中的停留时间也不是十分关键，但是优选仅为大约0.01-0.1秒。
活性物质或组合物与溶剂之间的比例不是非常关键，并且该比例取决于特别选择的组分。显而易见的是溶剂量必须足以确保活性物质或组合物在超临界溶剂中完全溶解。水相和溶剂相之间的比例(即水相进料流和含有活性物质或组合物的超临界溶剂之间的比例)也不是十分关键。用本发明方法制备的最终分散体中的活性物质或组合物的浓度上限最终取决于活性物质或组合物在溶剂中的溶解度。可以制备含有至多大约50重量％活性物质或组合物的分散体。调整工艺条件宜使最终分散体含有大约0.1-20重量％活性物质或组合物，例如大约10重量％。
水相以及某种程度上还有溶剂相可能含有附加成分，例如载体，即牛明胶、猪明胶或鱼明胶、阿拉伯树胶、改性食用淀粉、纤维素衍生物、果胶、木质素磺酸盐；表面活性剂，例如糖酯、聚甘油脂肪酸酯、吐温；稳定剂或抗氧剂，例如抗坏血酸钠、抗坏血酰棕榈酸酯、dl-α-生育酚、混合生育酚、2，6-二叔丁基对甲酚(BHT)、叔丁基对羟基茴香醚(BHA)或乙氧基喹(EMQ)。
所得的分散体或乳液可以借助本质上已知的方法例如喷雾干燥或流化床进一步转化成固体粉末。
本发明提供的乳液或分散体可以应用于所有要求使用含有基本上不溶于水的脂溶性物质或组合物的精细分散形态的场合，例如用类胡萝卜素对食品或动物饲料上色。
以下实施例进一步说明了本发明。
                         实施例1
本实施例中采用了图1示意说明的装置。将1100g水、80g抗坏血酰棕榈酸酯、258g鱼明胶和550g糖装入2升不锈钢高压釜 5中。高压釜 5(预热至60℃/6巴氮气)中的水相经活塞泵 6(LABOMATIC HD 300)以90g/min的流速于150巴压力下送至换热器 7，在那里水相在6-12秒的停留时间内被加热至68.5℃。将50g β-胡萝卜素、6g α-生育酚、22.9g玉米油和740g二甲醚装入高压釜 1中。高压釜 1(预热至30℃/30巴氮气)中的油相经隔膜泵 2(Lewa Typ EL 3)于150巴压力下送至换热器 3，在那里油相在5-10秒的停留时间内被加热至155℃。水相和油相同时经过混合室 4和孔径0.25mm的孔 8到达停留区 9，在那里使混合物减压至常压，生成大约5-6kg/h的不含溶剂的β-胡萝卜素在明胶/糖基体中的水分散体。该分散体的平均颗粒尺寸为117nm(偏差为20nm)。
                         实施例2
本实施例中采用实施例1中描述的装置。将1100g水、80g抗坏血酰棕榈酸酯、258g鱼明胶和550g糖装入2升不锈钢高压釜 5中。高压釜 5(预热至60℃/6巴氮气)中的水相经活塞泵 6以120g/min的流速于149巴压力下送至换热器 7，在那里水相在6-12秒的停留时间内被加热至64℃。将50gβ-胡萝卜素、6g α-生育酚、22.9g玉米油和570g 1-丁烯装入高压釜 1中。高压釜 1(预热至30℃/30巴氮气)中的油相经隔膜泵 2于149巴压力下送至换热器 3，在那里油相在5-10秒的停留时间内被加热至127℃。水相和油相同时经过混合室 4和孔径为0.25mm的孔 8到达停留区 9，在那里使混合物减压至常压，生成大约7-8kg/h的不含溶剂的β-胡萝卜素在明胶/糖基体中的水分散体。该分散体的平均颗粒尺寸为223nm(偏差为87nm)。
                        实施例3
本实施例中采用实施例1中描述的装置。将1100g水、80g抗坏血酰棕榈酸酯、258g鱼明胶和550g糖装入2升不锈钢高压釜 5中。高压釜 5(预热至60℃/6巴氮气)中的水相经活塞泵 6以115g/min的流速于148巴压力下送至换热器 7，在那里水相在6-12秒的停留时间内被加热至63.7℃。将100gβ-胡萝卜素、12.5g α-生育酚、45.9g玉米油和590g反式丁烯装入高压釜 1中。高压釜 1(预热至30℃/30巴氮气)中的油相经隔膜泵 2于148巴压力下送至换热器 3，在那里油相在5-10秒的停留时间内被加热至137℃。水相和油相同时经过混合室 4和孔径为0.2mm的孔 8到达停留区 9，在那里使混合物减压至常压，生成大约6-7kg/h的不含溶剂的β-胡萝卜素在明胶/糖基体中的水分散体。所得分散体的平均颗粒尺寸为223nm(偏差为73nm)。
                        实施例4
本实施例中采用实施例1中描述的装置。将130g水、62g抗坏血酰棕榈酸酯、242g鱼明胶和384g糖装入2升不锈钢高压釜 5中。高压釜 5(预热至60℃/6巴氮气)中的水相经活塞泵 6以60g/min的流速于109巴压力下送至换热器 7，在那里水相在6-12秒的停留时间内被加热至75.8℃。将25g番茄红素、3.1g α-生育酚、11.5g玉米油和740g二甲醚装入高压釜 1中。高压釜 1(预热至30℃/30巴氮气)中的油相经隔膜泵2于109巴压力下送至换热器 3，在那里油相在5-10秒的停留时间内被加热至137℃。水相和油相同时经过混合室 4和孔径为0.25mm的孔 8到达停留区 9，在那里使混合物减压至常压，生成大约3-4kg/h的不含溶剂的番茄红素在明胶/糖基体中的水分散体。所得分散体的平均颗粒尺寸为171nm(偏差为60nm)。
                        实施例5
本实施例中采用实施例1中描述的装置。将330g水、68g抗坏血酰棕榈酸酯、188g卵磷脂和1412g lebboline装入2升不锈钢高压釜 5中。高压釜 5(预热至60℃/6巴氮气)中的水相经活塞泵6以120g/min的流速于192巴压力下送至换热器 7，在那里水相在6-12秒的停留时间内被加热至67℃。将50g β-胡萝卜素、9.4g α-生育酚、34.4g玉米油和740g二甲醚装入高压釜 1中。高压釜 1(预热至30℃/30巴氮气)中的油相经隔膜泵 2于192巴压力下送至换热器 3，在那里油相在5-10秒的停留时间内被加热至170℃。水相和油相同时经过混合室 4和孔径为0.2mm的孔 8到达停留区 9，在那里使混合物减压至常压，生成大约7-8kg/h的不含溶剂的β-胡萝卜素在卵磷脂/lebboline基体中的水分散体。该分散体的平均颗粒尺寸为174nm(偏差为36nm)。

Claims (9)

1.一种制备分散体的方法，其包括将这种活性物质或组合物在二甲醚或C4烃或其混合物中的溶液以其超临界或近临界状态分散在水相中、使混合物减压并从气态溶剂中分离出分散体。
2.根据权利要求1的方法，其中活性物质或组合物选自脂溶性维生素、药物、类胡萝卜素和多不饱和脂肪酸。
3.根据权利要求1或2的方法，其中活性物质或组合物为类胡萝卜素。
4.根据权利要求3的方法，其中类胡萝卜素为β-胡萝卜素。
5.根据权利要求1-4中任何一项的方法，其中溶剂为二甲醚。
6.根据权利要求1-4中任何一项的方法，其中溶剂为1-丁烯。
7.根据权利要求1-4中任何一项的方法，其中溶剂为反式丁烯。
8.根据权利要求1-7中任何一项的方法，其中分散颗粒的平均直径为大约20至大约300nm。
9.一种根据权利要求1-8中任何一项的方法，基本如本文所述，特别参考附图和实施例所述。
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