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CN108567745A - 一种含有活性成分的冻干赋形制剂及其制备方法 - Google Patents

一种含有活性成分的冻干赋形制剂及其制备方法 Download PDF

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CN108567745A
CN108567745A CN201710142592.4A CN201710142592A CN108567745A CN 108567745 A CN108567745 A CN 108567745A CN 201710142592 A CN201710142592 A CN 201710142592A CN 108567745 A CN108567745 A CN 108567745A
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董玲
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Changzhou Pomelo Shield Industrial Investment Co Ltd
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Abstract

本发明涉及一种含有活性成分的冻干赋形制剂及其制备方法，特别是一种含有黄酮、黄酮苷类和醌类的活性成分的配方，并通过一定的溶解体系将其溶解后、配合粘结剂制成的冻干赋形制剂及其制备方法。

Description

一种含有活性成分的冻干赋形制剂及其制备方法
技术领域
本发明涉及一种含有活性成分的冻干赋形制剂及其制备方法，特别是一种含有黄酮、黄酮苷类和醌类的活性成分的配方，并通过一定的溶解体系将其溶解后、配合粘结剂制成的冻干赋形制剂及其制备方法。
背景技术
在食品、保健食品、药品、日用化学品中，黄酮、黄酮苷类和醌类是常用的活性物质，其虽然可溶于水，但需要具备一定条件，如黄酮苷类可溶于碱水但不溶于酸性水。这类活性物质，会因为其溶解性等限制，而大大限制了制剂形态和工艺，使其生产成本不好控制。
冻干赋形技术是指在可流动的液体、半固体或固体的活性成分中加入骨架支持剂以及粘结剂，或所述可流动的液体、半固体或固体中本身含有粘结剂及骨架支持剂，然后将其灌注到成型模具中，通过冷冻干燥工艺得以成型的技术，通过冻干赋形技术制备的制剂称作冻干赋形制剂。
由于该类制剂采用冷冻干燥工艺，可以保护不稳定活性成分不被破坏，同时通过水分升华产生大量微孔和孔道，可以具有很快的崩解和溶解速度，因此受到了广泛应用，可以应用于口腔崩解片、速释片、咀嚼片、特殊化妆品、医疗器械、保健品等多个领域。
发明人锐意创新，进行了大量深入的研究和试验工作，基于冻干制剂制造工艺的原理进行工艺优化，并通过对配方的研究，提供了一套使用溶解体系配合的配方，使此类活性物质可以应用于冻干赋形制剂，并保证其使用时的吸收性、吸収速度和使用效果。
发明内容
一种含有活性成分的冻干赋形制剂，其特征在于，由活性成分、溶解体系和粘结剂组成。
所述活性成分选自黄酮、黄酮苷类和醌类的其中一种或多种组合，其质量百分比为0.01％-99％，优选0.01％-50％，0.1％-50％，0.1％-30％，0.1％-10％，0.5％-50％，0.5％-30％，0.5％-10％，0.5％-5％，1％-50％，1％-30％，1％-10％，最优选0.5％-50％。
所述溶解体系选自酸性缓冲剂和碱性缓冲剂中的一种或两种。
所述酸性缓冲剂可以选自氨基酸类、无机酸、有机酸中一种或多种组合；可以是但不限于甘氨酸、盐酸、邻苯二甲酸、柠檬酸、柠檬酸钠、乙酸、乙酸钠中的一种或多种组合。
所述碱性缓冲剂可以选自碱、碳酸钠、碳酸氢钠、磷酸盐、硼酸、硼砂、氨基酸类、烷烃、巴比妥钠中一种或多种组合。
所述粘结剂，可以为冻干粘结剂或冻干粘结剂和低温粘结剂的组合。
所述冻干粘结剂为人工或天然高分子聚合物、无机物凝胶剂、纤维素醚类、改性淀粉类、透明质酸类、白蛋白、右旋糖酐、壳聚糖及其不同分子量产物、海藻酸钠、PVP、PVA、聚乙二醇、琼脂、聚氨基酸、聚糖或它们的组合；所述低温粘结剂为C1-C16的醇、油脂、表面活性剂、高分子聚合物中的一种或多种组合。
所述C1-C6的醇选自丙二醇、丁二醇、丙三醇、1、2丁二醇、1、2丙二醇、1、3丁二醇、戊二醇、聚乙二醇、聚甘油、双甘油等中的一种或多种。
所述油脂选自聚二甲基硅氧烷、聚甘油-6八硬脂酸酯、辛酸/癸酸甘油三酯、甘油三(乙基己酸)酯、二异硬脂醇苹果酸酯、聚甘油-2三异硬脂酸酯、二聚季戊四醇三-聚羟基硬脂酸酯、植物甾醇油酸酯、矿脂、黄原胶、甘油三(山嵛酸/异硬脂酸/二十烷二酸)酯、卵磷脂、氢化卵磷脂、氢化聚癸烯、甲氧基肉桂酸乙基己酯、奶油、貂油、鹅油、鲨鱼肝油、扁桃油、杏仁油、橄榄油、芝麻油、茶籽油、棕榈酸乙基己酯、牛油果树果酯、月桂酸己酯、碳酸二辛酯、GTCC、辛酸丙基庚酯、油醇或甘油三酯等中的一种或多种。
所述表面活性剂选自吐温类成分、司盘类成分、PEG-20甘油三异硬脂酸酯、聚甘油-10二硬脂酸酯、聚甘油-2油酸酯、椰油酰甘氨酸钾、月桂酰甘氨酸钾等中的一种或多种。
所述高分子聚合物为海藻酸钠、羊毛脂、琼脂、聚乙烯醇丙烯酸甲酯接枝共聚物、卡波姆、卡波树脂、透明质酸钠、透明质酸、聚乙烯吡咯烷酮、聚乙烯醇、聚乙二醇、聚氧化乙烯、改性石蜡、聚丙烯酰胺、聚丙烯酸钠、聚丙烯酸酯和聚丙烯酸及其衍生物等中的一种或多种。
所述无机物凝胶剂为硅藻土、膨润土、蒙脱石、锂基蒙脱石、硅凝胶中的一种或多种。
所述胶类粘结剂为胶原、明胶、水解明胶、阿拉伯胶、黄原胶、大豆蛋白胶、小核菌胶、生物糖胶、卡拉胶、瓜尔胶、结冷胶、果胶、魔芋胶、角叉菜胶、刺槐豆胶、树胶、槐豆胶等中的一种或多种。
所述的纤维素醚类粘结剂为微晶纤维素、羧甲基纤维素、羧乙基纤维素、羟乙基甲基纤维素、羟丙基甲基纤维素等中的一种或多种。
所述改性淀粉类粘结剂选自聚丙烯酸钠接枝淀粉、普鲁兰糖、羟丙基淀粉、羟丙基甲基淀粉、预胶化淀粉、直链淀粉、羧甲基淀粉、羟乙基淀粉、羟丙基淀粉等中的一种或多种。
所述聚氨基酸选自聚谷氨酸、聚丙氨酸、聚天冬氨酸、聚赖氨酸等中的一种或多种。
所述聚糖选自岩藻多糖、菊糖、葡聚糖等中的一种或多种。
上述配方，还可以进一步在配方中添加其他辅料，选自骨架支持剂，肤感改良剂，抗氧化剂，矫味剂，香精，跨黏膜、透皮吸收促进剂和pH调节剂中的一种或多种组合。
所述骨架剂选自糖(如麦芽糖、海藻糖等)、糖醇(如甘露醇、山梨醇)、2-12碳原子的氨基酸(如甘氨酸、丙氨酸、谷氨酸等)以及无机盐(如磷酸钠、硅酸铝等)中的任一种或数种混合物。
所述肤感改良剂选自聚甲基硅倍半氧烷、木薯淀粉、二C12-13醇苹果酸酯、二肉豆蔻醇酒石酸酯、PPG-15硬脂醇醚、锦纶-12、欧洲越桔籽油等具有改善肤感的物质中的任一种或数种混合物。
所述的抗氧化剂选自维生素C、维生素E、花青素、白藜芦醇、谷胱甘肽、超氧化物歧化酶、酵母菌/大米发酵产物滤液、植物提取物、白僵菌提取物、白松露菌提取物、果蔬提取物、植物来源的多元酚类化合物等具有抗氧化功效物质中的任一种或数种的混合物。
所述矫味剂和香精选自薄荷味、巧克力味、果蔬味、花草香味、植物香味、香草味、咖啡味、茶味、玉米味、柠檬味、牛奶味等香精或以上一种或几种香味的混合物。
所述的跨黏膜或透皮吸收促进剂选自卵磷脂、吐温、司盘中的任一种或数种的混合物。
所述的PH调节剂选自柠檬酸、山梨酸、酒石酸、乳酸、苹果酸、碳酸氢钠、碳酸钠，磷酸氢二钠、磷酸钙、磷酸钾、磷酸三镁等中的任何一种或数种的混合物。
上述冻干赋形制剂的制备方法：
A、方法1
a)将水、溶解体系、活性成分、辅料形成的溶液、乳液或者悬浊液，定容、脱气；
b)使用定量灌装泵，将a)注入到定量成型模具中，进行脱气；
c)将b)冷冻干燥，除去溶剂，得到包含活性油和稳定剂的稳定冻干制剂，且冻干制剂可以脱离模具，进行内包装。
B、方法2
a)制备软冰混合物：
将活性成分、溶解体系和辅料，与溶媒全部或部分混合，进行凝冻，得到软冰混合物1；
b)剩余活性成分、溶解体系和辅料，与溶媒部分混合，进行低温冷冻粉碎或低温喷雾，得到冰粉2；
c)剩余活性成分、辅料，作为干粉3；
d)将a)、b)、c)的一种或多种组合混合，得到的所有软冰混合物；
e)使用一定模具定型，得到定型后的混合物4，脱模；
f)对混合物4进行冷冻干燥，得到冻干制剂。
C、方法3
a)将水、活性成分、溶解体系及辅料形成的溶液、乳液或悬浊液，定容、脱气；
b)使用定量灌装泵，在内部温度处于溶液共晶点以下的舱体内进行滴注，使其滴液时迅速冻结；
c)将已冻结的溶液进行冷冻干燥，得到包含活性油和稳定剂的稳定冻干制剂。
所述冻干赋形制剂，可以为任意形状，可以为片剂形状、胶囊剂形状、软胶囊形状、球形、椭球形或者各种人物、动物、植物、食物、图形标识或卡通形象。
所述冻干赋形制剂产品，可以适用于日用化学品、药品、保健品、食品、以及医疗器械领域。
具体实施方式
以下通过实施例进一步说明本发明，但本发明并不仅仅限于此。
实施例1
黄芩苷25g，甘露醇46g、普鲁兰56g、磷酸氢二钠58g、柠檬酸6.7g，加水定容至2L，脱气，得到混合溶液，使用移液枪，将混合溶液灌注入片形模具中，脱气、预冻、冷冻干燥、除去溶剂后，得到黄芩苷外用美白冻干赋形制剂。
实施例2
甘露醇100g，透明质酸钠4g，卡波姆10g，三乙醇胺4g，黄芩苷25g，磷酸氢二钠58g，柠檬酸6.7g加水定容至2L，脱气，得到混合溶液，使用蠕动泵，在内部温度处于溶液共晶点以下的舱体内进行滴注，使其滴液时迅速冻结，将已冻结的溶液进行冷冻干燥，得到黄芩苷外用美白冻干赋形制剂。
实施例3
甘露醇15％，黄芩苷0.94％，甘油15％，磷酸氢二钠2.15％，柠檬酸0.25％，于水中溶解均匀成混合溶液，将液体在-10℃条件下凝冻，形成软冰混合物；将软冰混合物使用定量灌装泵装入经过预冷的球型模具定量；采用液氮循环降温方式，使定量组分在-205℃环境下脱离模具；将脱离模具的组分进行冻干，得到黄芩苷外用美白冻干赋形制剂。
实施例4
芦丁2％，甘油15％，磷酸氢二钠2.15％，柠檬酸0.25％，于水中溶解均匀成混合溶液，将液体在-7℃条件下凝冻，形成软冰混合物；改性木薯淀粉15％作为干粉，加入软冰混合物，混合均匀；将混合后的软冰混合物使用定量灌装泵装入经过预冷的球型模具定量；采用液氮循环降温方式，使定量组分在-205℃环境下脱离模具；将脱离模具的组分进行冻干，得到芦丁冻干赋形制剂。
实施例5
紫草素10g，甘露醇46g、普鲁兰56g、磷酸氢二钠58g、磷酸二氢钠29g，甘氨酸7.5g，盐酸3.6g加水定容至2L，脱气，得到混合溶液，使用移液枪，将混合溶液灌注入片形模具中，脱气、预冻、冷冻干燥、除去溶剂后，得到紫草素冻干赋形制剂。
实施例6
大黄素3％，磷酸二氢钠2.15％，柠檬酸0.25％，于水中溶解均匀成混合溶液，使用低温粉碎制作冰粉；改性木薯淀粉15％、瓜尔豆胶0.2％，甘油15％，于水中溶解均匀成混合溶液，将液体在-7℃条件下凝冻，形成软冰混合物；将冰粉混入软冰混合物，搅拌均匀；将混合后的软冰混合物使用定量灌装泵装入经过预冷的球型模具定量；采用液氮循环降温方式，使定量组分在-205℃环境下脱离模具；将脱离模具的组分进行冻干，得到大黄素冻干赋形制剂。
本发明所涉及的成分组成、形态和制备方式并不限于实施例中所列举的形式，实施例仅为本发明的较佳实施例而已，不能以此限定保护范围。凡以本发明的权利要求范围所述的简单的或等效的变化及修饰，皆属于本发明的保护范围。

Claims (10)

1.一种含有活性成分的冻干赋形制剂，其特征在于，由活性成分、溶解体系和粘结剂组成。
2.权利要求1所述的冻干赋形制剂，其特征在于，所述活性成分选自黄酮、黄酮苷类和醌类的其中一种或多种组合，其质量百分比为0.01％-99％；所述溶解体系选自酸性缓冲剂和碱性缓冲剂中的一种或两种；所述粘结剂，可以为冻干粘结剂或冻干粘结剂和低温粘结剂的组合。
3.权利要求1、2所述的冻干赋形制剂，其特征在于，所述酸性缓冲剂可以选自氨基酸类、无机酸、有机酸中一种或多种组合；所述碱性缓冲剂可以选自碱、碳酸钠、碳酸氢钠、磷酸盐、硼酸、硼砂、氨基酸类、烷烃、巴比妥钠中一种或多种组合。
4.权利要求1-3所述的冻干赋形制剂，其特征在于，所述冻干粘结剂为人工或天然高分子聚合物、无机物凝胶剂、纤维素醚类、改性淀粉类、透明质酸类、白蛋白、右旋糖酐、壳聚糖及其不同分子量产物、海藻酸钠、PVP、PVA、聚乙二醇、琼脂、聚氨基酸、聚糖或它们的组合；所述低温粘结剂为C1-C16的醇、油脂、表面活性剂、高分子聚合物中的一种或多种组合。
5.根据权利要求1-4所述的配方，其特征在于，还可以进一步在配方中添加其他辅料，选自骨架支持剂，肤感改良剂，抗氧化剂，矫味剂，香精，跨黏膜、透皮吸收促进剂和pH调节剂中的一种或多种组合。
6.根据权利要求1所述的制备方法，其特征在于，有如下制备方法：
A、方法1
a)将水、活性成分、溶解体系、辅料形成的溶液、乳液或者悬浊液，定容、脱气；
b)使用定量灌装泵，将a)注入到定量成型模具中，进行脱气；
c)将b)冷冻干燥，除去溶剂，得到包含活性油和稳定剂的稳定冻干制剂，且冻干制剂可以脱离模具，进行内包装。
B、方法2
a)制备软冰混合物：
将活性成分、溶解体系和辅料，与溶媒全部或部分混合，进行凝冻，得到软冰混合物1；
b)剩余活性成分、溶解体系和辅料，与溶媒部分混合，进行低温冷冻粉碎或低温喷雾，得到冰粉2；
c)剩余活性成分、辅料，作为干粉3；
d)将a)、b)、c)的一种或多种组合混合，得到的所有软冰混合物；
e)使用一定模具定型，得到定型后的混合物4，脱模；
f)对混合物4进行冷冻干燥，得到冻干制剂。
C、方法3
a)将水、活性成分、溶解体系及辅料形成的溶液、乳液或悬浊液，定容、脱气；
b)使用定量灌装泵，在内部温度处于溶液共晶点以下的舱体内进行滴注，使其滴液时迅速冻结；
c)将已冻结的溶液进行冷冻干燥，得到包含活性油和稳定剂的稳定冻干制剂。
7.由权利要求1-6任意一项配方和/或制备方法制备得到的产品。
8.根据权利要求7所述的产品，其特征在于，其为任意形状。
9.根据权利要求8所述的产品，其特征在于，其为片剂形状、胶囊剂形状、软胶囊形状、球形、椭球形或者各种人物、动物、植物、食物、图形标识或卡通形象。
10.根据权利要求1-9所述的产品，其特征在于，可以适用于日用化学品、药品、保健品、食品、以及医疗器械领域。
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CN110025623A (zh) * 2019-03-21 2019-07-19 李和伟 一种冻干制剂及其制备方法和应用
CN111214444A (zh) * 2018-11-23 2020-06-02 山东坦途农业科技有限公司 一种含有矫味剂的三七冻干赋形制剂及其制备方法
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CN112168889A (zh) * 2019-07-04 2021-01-05 常州伟博海泰生物科技有限公司 一种抗痤疮冻干赋形制剂及其制备方法
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CN111214444A (zh) * 2018-11-23 2020-06-02 山东坦途农业科技有限公司 一种含有矫味剂的三七冻干赋形制剂及其制备方法
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