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CN103402491B - 改进的粉末状维生素e制剂 - Google Patents

改进的粉末状维生素e制剂 Download PDF

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CN103402491B
CN103402491B CN201180068597.8A CN201180068597A CN103402491B CN 103402491 B CN103402491 B CN 103402491B CN 201180068597 A CN201180068597 A CN 201180068597A CN 103402491 B CN103402491 B CN 103402491B
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马丁·伽蒂恩特
托马斯·林德曼
米沙·施温格尔
卡尔·曼弗雷德·沃勒科
凯·尔本
斯蒂芬妮·盖尔森
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Abstract

本发明涉及改进的维生素E制剂，以及所述制剂的生产。

Description

改进的粉末状维生素E制剂
本发明涉及改进的维生素E制剂以及所述制剂的生产。
在本专利申请的上下文中，术语“维生素E”涵盖了维生素E及其酯(例如维生素E醋酸酯)。
维生素E制剂可以作为不同种类的制剂。它们可以是液体和固体。具有大量维生素E的维生素E制剂通常用于配制终端市场用的液体组合物或固体组合物。这种终端市场组合物可以是食品、饲料、个人护理产品等等。本发明公开并要求保护的制剂优选地被用于食品和饲料产品中以及个人护理产品中。
由于粉末的小颗粒尺寸，粉末状形式的维生素E制剂确实有爆炸的危险。即使当粉末包含突出量的较大颗粒时，总有一定量的小颗粒存在。这些小颗粒导致爆炸风险。
粉尘爆炸在使用粉末的任何过程中都是一个巨大的风险。因此，需要具有低爆炸风险的粉末状制剂。不过粉末状制剂必须还具有必要的(以及有利的)粉末特征，例如可自由流动、易于运输、易于配药等等。
令人惊奇的是，业已发现包含一种或多种特定化合物和载体材料的粉末状维生素E制剂确实具有低的爆炸风险。
因此，本申请涉及粉末状制剂(I)，其包含：
(i)基于粉末状制剂的总重量，至少50重量-％(wt-％)的维生素E和/或维生素E衍生物；和
(ii)基于粉末状制剂的总重量，0.5wt-％至8wt-％的至少一种辅助化合物，所述辅助化合物选自由硫酸铝铵、硫酸铝钾、醋酸铵、亚硫酸氢铵、碳酸铵、氯化铵、磷酸二氢铵、碳酸氢铵、膨润土、蒙脱土、铝酸钙、碳酸钙、硅酸钙、合成的硫酸钙二水合物、硫酸钙、高岭石粘土(如高岭土)、硅藻土、珍珠岩、亚硫酸氢钾、碳酸氢钾、硫酸钾、碳酸钾、海泡石粘土、硅酸、合成的硅铝酸钠、硫铝酸钠(sodiumaluminosulfate)、硫酸氢钠、碳酸钠、氯化钠、碳酸氢钠、硫酸钠、蛭石、碳酸钙、碳酸镁、钙质海藻、氧化镁、硫酸镁、磷酸二钙、磷酸三钙、磷酸一二钙、脱氟磷酸岩、磷酸一钙、磷酸镁钙、磷酸一铵、磷酸镁、磷酸镁钙钠(sodium-calcium-magnesiumphosphate)、磷酸一钠、甘油、丙二醇(E1520)、三醋酸甘油酯(E1518)、山梨糖醇(E420)、聚葡萄糖、乳酸和尿素组成的组；和
(iii)基于粉末状制剂的总重量，至少40wt-％的载体材料。
很显然，所有的wt-％相加总和为100。
维生素E衍生物通常为酯(优选地维生素E醋酸酯)。
在本发明的上下文中，特定的化合物(ii)还被定义为辅助化合物。
优选地，辅助化合物具有10μm-100μm的平均颗粒尺寸(d0.5)(在粉末制剂中)。
通常通过标准化的方法(EN13821：2002(粉尘/空气混合物的最小点火能的测定(Determinationofminimumignitionenergyofdust/airmixtures)))来测量粉末(粉尘)的爆炸危险性。这是用于测定本专利申请中所有MIE值的方法。该方法可以测定粉末的最小点火能(MIE)。MIE为点燃可燃蒸气、气体或粉尘云所需的最小能量，例如由于静电放电引起。MIE用焦耳(J)或毫焦耳(mJ)计。
根据EN13821：2002中步骤测量的粉末颗粒的平均尺寸为≤63μm。
通过使用可从AdolfKühnerAG(Birsfelden，CH)购得的改性的Hartmann管(MIKE3型)来测定本专利申请中的所有MIE值。该设备是为允许非常低的点火能的测量而专门设计的。这可以通过安装不同的电容器来实现。电容器被设计来储存1mJ、3mJ、10mJ、30mJ、100mJ、300mJ和1000mJ的能量。
当测量可商业购买的粉末状维生素E制剂的MIE时，它们通常在1-3mJ的范围内。这意味着非常低的能量便足以引发爆炸。
另一方面，根据本发明的制剂具有在10-1000mJ的范围内(或甚至大于1000mJ)的MIE值。
因此，本发明涉及制剂(II)，其为具有10-1000mJ的MIE值(通过EN13821：2002的方法测定)的制剂(I)。MIE值甚至可以高于1000mJ。
根据本发明的制剂为粉末。但是根据生产的工艺以及储存条件，制剂可以包含一些水。基于制剂的总重量，水含量通常在5wt-％以下。因此，本发明的另一个实施方式涉及如上所述的维生素E制剂，其中基于制剂的总重量，存在0至5wt-％的水。
优选地，粉末状制剂不包含上面所公开的之外的其他成分/化合物。它们不包含任何常用的稳定剂、表面活性成分或糖。
维生素E及其酯可以来自天然来源或者它们可以是合成的。由于分离过程或生产过程的性质，可能存在痕量的副产物。
根据本发明的制剂中所用的载体是公知且常用的载体材料。合适的载体材料为合成法生产的沉淀二氧化硅。该载体由多孔颗粒组成。其他合适的载体为蛋白质、淀粉、木素磺化盐和树胶(gums)。
本发明的优选实施方式为制剂(III)，其包含：
(i)基于粉末状制剂的总重量，至少50wt-％的维生素E和/或维生素E衍生物；和
(ii)基于制剂的总重量，0.5wt-％至8wt-％的至少一种化合物，所述化合物选自由磷酸二氢铵、(纯化的)硅藻土、碳酸氢钾、硫酸钾、碳酸钾、氯化钠和碳酸氢钠组成的组；和
(iii)基于粉末状制剂的总重量，至少40wt-％的载体材料，所述载体材料选自由合成法生产的沉淀二氧化硅、蛋白质、淀粉、木素磺化盐和树胶组成的组。
更优选的是制剂(IV)，其为具有10-1000mJ的MIE值(通过EN13821：2002的方法测定)的制剂(III)。MIE值甚至可以高于1000mJ。
本发明的一个更优选的实施方式涉及制剂(V)，其由以下组成：
(i)基于粉末状制剂的总重量，至少50wt-％的维生素E和/或维生素E衍生物；和
(ii)基于粉末状制剂的总重量，0.5wt-％至8wt-％的至少一种辅助化合物，所述辅助化合物选自由硫酸铝铵、硫酸铝钾、醋酸铵、亚硫酸氢铵、碳酸铵、氯化铵、磷酸二氢铵、碳酸氢铵、膨润土、蒙脱土、铝酸钙、碳酸钙、硅酸钙、合成的硫酸钙二水合物、硫酸钙、高岭石粘土(如高岭土)、硅藻土、珍珠岩、亚硫酸氢钾、碳酸氢钾、硫酸钾、碳酸钾、海泡石粘土、硅酸、合成的硅铝酸钠、硫铝酸钠(sodiumaluminosulfate)、硫酸氢钠、碳酸钠、氯化钠、碳酸氢钠、硫酸钠、蛭石、碳酸钙、碳酸镁、钙质海藻、氧化镁、硫酸镁、磷酸二钙、磷酸三钙、磷酸一二钙、脱氟磷酸岩、磷酸一钙、磷酸镁钙、磷酸一铵、磷酸镁、磷酸镁钙钠(sodium-calcium-magnesiumphosphate)、磷酸一钠、甘油、丙二醇(E1520)、三醋酸甘油酯(E1518)、山梨糖醇(E420)、聚葡萄糖、乳酸和尿素组成的组；和
(iii)基于粉末状制剂的总重量，至少40wt-％的载体材料，所述载体材料选自由合成法生产的沉淀二氧化硅、蛋白质、淀粉、木素磺化盐和树胶组成的组；以及
(iv)基于粉末状制剂的总重量，0至5wt-％的水。
更优选的是制剂(VI)。其为具有10-1000mJ的MIE值(通过EN13821：2002的方法测定)的制剂(V)。MIE值甚至可以高于1000mJ。
此外优选的是制剂(VI’)，其为其中辅助化合物具有10μm-100μm的平均颗粒尺寸(d0.5)的制剂(VI)。
通过MalvernMasterSizer2000测量平均颗粒尺寸。在该激光衍射测量中，聚焦的激光束穿过颗粒。这些颗粒在与其尺寸成反比的角度上使光散射。然后通过一系列光敏检测器来测量散射光的角强度。散射强度vs.角度的图是用来计算颗粒尺寸的主要信息源。为了测量干燥材料，例如所采用的添加剂，使用干粉进料器(MalvernScirocco)。
本发明的一个特别优选的实施方式涉及制剂(VII)，其由以下组成：
(i)基于粉末状制剂的总重量，至少50wt-％的维生素E和/或维生素E衍生物；和
(ii)基于粉末状制剂的总重量，0.5wt-％至8wt-％的至少一种辅助化合物，所述辅助化合物选自由磷酸二氢铵、(纯化的)硅藻土、碳酸氢钾、硫酸钾、碳酸钾、氯化钠、硫酸钠和碳酸氢钠组成的组，
(iii)基于粉末状制剂的总重量，至少40wt-％的载体材料，所述载体材料选自由合成法生产的沉淀二氧化硅、蛋白质、淀粉、木素磺化盐和树胶组成的组；以及
(iv)基于粉末状制剂的总重量，0至5wt-％的水。
更优选的是制剂(VII)，其为具有10-1000mJ的MIE值(通过EN13821：2002的方法测定)的制剂(VI)。MIE值甚至可以高于1000mJ。
此外优选的是制剂(VII’)，其为其中辅助化合物具有10μm-100μm的平均颗粒尺寸(d0.5)的制剂(VII)。
为了生产根据本发明的粉末(制剂(I)、(II)、(III)、(IV)、(V)、(VI)、(VI′)、(VII)和(VII′))，可以将维生素E(和/或维生素E衍生物)喷到载体材料上，然后加入至少一种辅助化合物并将制剂掺合在一起。
也可以将维生素E(和/或维生素E衍生物)喷到至少一种载体材料与至少一种辅助化合物的混合物上。
所有上面公开的制剂(I)、(II)、(III)、(IV)、(V)、(VI)、(VI′)、(VII)和(VII′)本身可以用于食物产品、饲料产品和个人护理产品中。
所有上面公开的制剂(I)、(II)、(III)、(IV)、(V)、(VI)、(VI′)、(VII)和(VII′)本身可以用于食物产品、饲料产品和个人护理产品的生产中。
通过以下实施例来说明本发明。所有温度都以℃给出，并且所有份数和百分比都与重量相关。
实施例
实施例1
在室温(RT)下将63.3g沉淀二氧化硅填充到适当的混合机(Diosna-BlenderP1/6，容积为0.5L)中。在非常小心地混合二氧化硅(100-150rpm)下，在5-10分钟内使温度增大到约50℃。通过喷嘴的方式将79.2g的预热过的dl-α-生育酚-乙酸酯(工业级，95.5％dl-α-生育酚-乙酸酯＝维生素E衍生物)喷到二氧化硅上。该过程在约5分钟内在混合(100-150rpm)下进行。在该工艺步骤中，温度略微地增大到约55℃。在50-55℃(100-150rpm)下将混合物混合额外的20分钟。然后，加入7.5g碳酸氢钾作为添加剂(添加剂的中值颗粒尺寸：414μm)，并且将该最终的混合物混合10分钟(50-55℃，100-150rpm)。将所获得的自由流动的白色粉末填充到容器中。
根据上述EN13821：2002来分析粉末，并发现最小点火能为10-30mJ，通过HPLC测定维生素E含量，发现为50.9％。
实施例2
在RT下将63.3g沉淀二氧化硅填充到适当的混合器(Diosna)中。加入7.5g碳酸氢钾作为添加剂(添加剂的中值颗粒尺寸：414μm)。将该混合物混合5-10分钟(150rpm)，在该工艺步骤中使温度增大到约50℃。
通过喷嘴的方式将79.2g的预热过的dl-α-生育酚-乙酸酯(工业级，95.5％dl-α-生育酚-乙酸酯)喷到二氧化硅-添加剂混合物上。该过程在约5分钟内在混合(100-150rpm)下进行。在该过程中，温度略微地增大到约55℃。在50-55℃(100-150rpm)下将混合物混合20分钟。
根据EN13821：2002来分析粉末，并发现最小点火能为10-30mJ，通过HPLC测定维生素E含量，发现为51.0％。
实施例3
在RT下将63.3g沉淀二氧化硅填充到适当的混合机(Diosna)中。在非常小心地混合二氧化硅(100-150rpm)下，在5-10分钟内使温度增大到约50℃。通过喷嘴的方式将79.2g的预热过的dl-α-生育酚-乙酸酯(工业级，95.5％dl-α-生育酚-乙酸酯)喷到二氧化硅上。该过程在约5分钟内在混合(100-150rpm)下进行。在该工艺步骤中，温度略微地增大到约55℃。在50-55℃(100-150rpm)下将混合物混合额外的20分钟。然后，加入7.5g氯化钠，并且将该最终的混合物混合10分钟(50-55℃，100-150rpm)。将所获得的自由流动的白色粉末填充到容器中。
根据上述EN13821：2002来分析粉末，并发现最小点火能为10-30mJ，通过HPLC测定维生素E含量，发现为50.5％。
实施例4
在RT下将63.3g沉淀二氧化硅填充到适当的混合器(Diosna)中。加入7.5g氯化钠作为添加剂。将该混合物混合5-10分钟(150rpm)，在该工艺步骤中温度增大到约50℃。通过喷嘴的方式将79.2g的预热过的dl-α-生育酚-乙酸酯(工业级，95.5％dl-α-生育酚-乙酸酯)喷到二氧化硅-添加剂混合物上。该过程在约5分钟内在混合(100-150rpm)下进行。在该过程中，温度略微地增大到约55℃。在50-55℃(100-150rpm)下将混合物混合20分钟。根据EN13821：2002来分析粉末，并发现最小点火能为10-30mJ，通过HPLC测定维生素E含量，发现为50.8％。
实施例5
在RT下将63.3g沉淀二氧化硅填充到适当的混合机(Diosna)中。在非常小心地混合二氧化硅(100-150rpm)下，在5-10分钟内使温度增大到约50℃。通过喷嘴的方式将79.2g的预热过的dl-α-生育酚-乙酸酯(工业级，95.5％dl-α-生育酚-乙酸酯)喷到二氧化硅上。该过程在约5分钟内在混合(100-150rpm)下进行。在该工艺步骤中，温度略微地增大到约55℃。在50-55℃(100-150rpm)下将混合物混合额外的20分钟。然后，加入7.5g磷酸二氢铵(添加剂)，并且将该最终的混合物混合10分钟(50-55℃，100-150rpm)。将所获得的自由流动的白色粉末填充到容器中。
根据上述EN13821：2002来分析粉末，并发现最小点火能为10-30mJ，通过HPLC测定维生素E含量，发现为51.9％。
实施例6
将9800g包含54％维生素E和46％二氧化硅的维生素E配制物填充入适当的混合机(Nauta)中，并加入200g具有54μm的平均颗粒尺寸(d0.5)(通过激光衍射分析)的氯化钠，并且使混合物混合10分钟。将所获得的自由流动的白色粉末填充入容器中。
然后使用60m3/h的空气流和2000rpm的筛粉机轮的旋转速度在适当的装置(AlpineMultiprocessunit100AFG/50ATP)中将混合物空气分级(airclassified)，并且收集细料。通过激光衍射评估，颗粒平均为27μm，氯化钠含量为16.0％，维生素E含量为33.4％。根据上述EN13821：2002分析细料，并且发现最小点火能为30-100mJ。

Claims (8)

1.粉末状制剂，其包含：
(i)基于所述粉末状制剂的总重量，至少50重量％的维生素E；和
(ii)基于所述粉末状制剂的总重量，0.5重量％至8重量％的至少一种辅助化合物，其中所述至少一种辅助化合物选自由磷酸二氢铵、碳酸氢钾和氯化钠组成的组；和
(iii)基于所述粉末状制剂的总重量，至少40重量％的载体材料，其中所述载体材料为由合成法生产的沉淀二氧化硅；和
其中所述辅助化合物或辅助化合物的混合物具有10-100μm平均颗粒尺寸d0.5。
2.如权利要求1所述的粉末状制剂，其还包含：
(iv)基于所述粉末状制剂的总重量，0至5重量％的水。
3.如前面权利要求中任意一项所述的粉末状制剂，其中所述制剂具有10-1000mJ的MIE值。
4.如前面权利要求中任意一项所述的粉末状制剂，其中所述制剂具有高于1000mJ的MIE值。
5.粉末状制剂，其由以下组成：
(i)基于所述粉末状制剂的总重量，至少50重量％的维生素E；和
(ii)基于所述粉末状制剂的总重量，0.5重量％至8重量％的至少一种辅助化合物，所述辅助化合物选自由磷酸二氢铵、碳酸氢钾和氯化钠组成的组；
(iii)基于所述粉末状制剂的总重量，至少40重量％的载体材料，其中所述载体材料为由合成法生产的沉淀二氧化硅；以及
(iv)基于所述粉末状制剂的总重量，0至5重量％的水。
6.如权利要求5所述的粉末状制剂，其中所述辅助化合物或辅助化合物的混合物具有10-100μm平均颗粒尺寸d0.5。
7.如权利要求1至6所述的制剂在食品、饲料或个人护理产品中的用途。
8.包含如权利要求1-6中任意一项所述的制剂的食品、饲料或个人护理产品。
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