CN101537187A - 花色苷磷脂复合物及其制备方法 - Google Patents
花色苷磷脂复合物及其制备方法 Download PDFInfo
- Publication number
- CN101537187A CN101537187A CN200810010689A CN200810010689A CN101537187A CN 101537187 A CN101537187 A CN 101537187A CN 200810010689 A CN200810010689 A CN 200810010689A CN 200810010689 A CN200810010689 A CN 200810010689A CN 101537187 A CN101537187 A CN 101537187A
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- Prior art keywords
- anthocyanin
- phospholipid
- phospholipids compound
- phospholipids
- preparation
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Abstract
本发明公开了一种花色苷磷脂复合物及其制备方法，包括花色苷磷脂复合物及其制备方法，属于药品保健品领域。其组成包括花色苷与磷脂，花色苷与磷脂的重量比为1∶1－20；制备方法采用介电常数小的有机溶剂溶解花色苷与磷脂混合物，经蒸发溶剂等工艺过程制成花色苷磷脂复合物。本发明花色苷磷脂复合物具有脂溶性，容易吸收，具有较高的生物利用度，可以制成乳剂等特点。
Description
技术领域
本发明涉及花色苷磷脂复合物及其制备方法，包括花色苷磷脂复合物及其制备方法，属于药品保健品领域。
背景技术
花色苷(anthocyanin)是一类广泛存在于植物中的水溶性色素，也被称作花色素类物质或花青素类物质，是植物的主要呈色物质，花色苷类色素也是自然界中大量存在的一种水溶性的植物色素物质，化学结构为2-苯基苯丙吡喃多羟基或多甲氧基取代物的糖苷，是一种类黄酮物质，通常包括天竺葵色素、矢车菊色素、飞燕草色素、芍药色素、矮牵牛色素、锦葵色素化学成分，代表性成分为花青素(anthocyanidin)-3-O-葡萄糖苷(C3G)、花青素鼠李糖苷、花青素阿拉伯糖苷、花青素半乳糖糖苷。来源上花色苷色素包括越桔花色苷色素、葡萄皮花色苷色素、黑加仑花色苷色素、黑米花色苷色素、桑葚花色苷色素、玫瑰茄花色苷色素、花生衣花色苷色素等。花色苷色素具有较强的抗氧化和清除自由基作用，可以降低高血脂大鼠的甘油脂水平，改善高甘油脂脂蛋白的分解代谢；抑制胆固醇吸收，降低低密度脂蛋白胆固醇含量；抗变异、抗肿瘤、抗过敏、保护胃粘膜。能够减轻眼疲劳、提高黑暗中视力以及视觉瞬间改变适应能力，对人视觉具有保护作用，对近视、单纯绿内障、视网膜炎色盲具有改善作用。
花色苷是花青素的糖苷衍生物，自然条件下游离的花青素(anthocyanidin)极少见，而常与一个或多个葡萄糖、鼠李糖、半乳糖、木糖、阿拉伯糖等通过糖苷键形成花色苷(anthocyanin)。花色苷基本结构如下：
R1和R2是H、OH或者OCH3，R3是糖基或H，R4是糖基或OH。
花色苷化学结构中含有多个羟基，具有较强的极性和一定的水溶性，脂溶性较差，化学稳定性差，随着存在环境的变化而发生转变。花色苷类物质通常生物利用度较低，不利于某些药用制剂的应用。为了提高其稳定性和生物利用度，我们采用制备成磷脂复合物的方法，提高花色苷的化学稳定性和生物利用度。
磷脂普遍存在于动植物细胞的原生质和生物膜中，对生物膜的生理活性和机体的正常代谢有重要的调节功能。磷脂是含磷酸根的脂类物质，属天然元素有机化合物，它既有表面活性，又具有生物活性，是特种表面活性剂。磷脂分子具有一个亲水性的头部和两条疏水长链，其结构式如下式：
其中R，R1是C14-C20的饱和或不饱和脂肪羧酸，而R2是胆碱、乙醇胺、丝氨酸等。
磷原子上的羟基中的氧原子有较强的得电子的倾向，而氮原子有较强的失电子的倾向，因此磷脂在一定条件下可与某些特定结构的药物成分生成复合物。目前研究能与磷脂形成稳定复合物且能有效改善母体药物生物学特性和药理活性的化学结构有；有机酸类化合物，如水杨酸、芳基乙酸、蛋白、多肽类、金属离子、以及中药的皂苷、黄酮类成分。关于花色苷磷脂复合物有关联的专利有中国专利CN99814446.0，用作抗动脉硬化的原花色素A2磷脂复合物，该专利未涉及本发明内容。
发明内容
本发明为了解决上述技术问题，提供了一种花色苷磷脂复合物及其制备方法。本发明花色苷磷脂复合物的稳定性好，改善了花色苷的脂溶性，使人体很容易吸收，最终增强其药理作用及疗效。
为了解决上述问题，本发明是通过如下技术方案实现的：
一种花色苷磷脂复合物，其组成包括花色苷与磷脂，花色苷与磷脂的重量比为1∶1-20。
所述花色苷磷脂复合物，其优选组成包括花色苷与磷脂，花色苷与磷脂的重量比为1∶2-4。
所述的花色苷是葡萄花色苷、黑米花色苷，越桔花色苷，黑加仑花色苷、山楂花色苷或桑葚花色苷中的一种或它们的任意比例混合物。
所述的花色苷是花青素鼠李糖苷、花青素半乳糖苷、花青素阿拉伯糖苷或花青素葡萄糖苷中的一种或它们的任意比例混合物。
所述的磷脂是大豆磷脂、蛋黄磷脂或大豆磷脂和蛋黄磷脂或它们的混合物；磷脂是磷脂酰胆碱、磷脂酰乙醇胺或磷脂酰丝氨酸中的至少一种；磷脂是二棕榈酰磷脂酰胆碱、二棕榈酰磷脂酰乙醇胺或二棕榈酰磷脂酰胆碱和二棕榈酰磷脂酰乙醇胺的混合物。
一种所述花色苷磷脂复合物的制备方法，它包括如下步骤：按所述重量比取花色苷与磷脂，于介电常数小的有机溶剂中混合，有机溶剂的使用量为1毫克花色苷不低于1ml的有机溶剂，反应的温度为10-80℃，反应时间为0.5-5小时，然后减压干燥或冷冻干燥，除去有机溶剂，得花色苷磷脂复合物。
所述的有机溶剂为氯仿、乙醚、丙酮、二氯甲烷、四氢呋喃、乙酸乙酯、正己烷、C1-C6直链或支链低级烷醇中的一种或一种以上混合物，其中C1-C6直链或支链低级烷醇为甲醇、乙醇、丙醇或丁醇。
所述的花色苷磷脂复合物加入常规辅料按常规方法制成颗粒剂、胶囊剂或片剂。
所述的花色苷磷脂复合物加入乳化剂和中链脂肪酸液体油或植物油，经乳化后制成花色苷磷脂复合物脂肪乳剂。
所述的花色苷磷脂复合物加入乳化剂和固体脂质、液体脂质或他们的混合物，制成脂质纳米粒。
本发明的优点和效果如下：本发明花色苷磷脂复合物，改善了花色苷的脂溶性，在正辛醇中的溶解度增加近十倍，具有类似磷脂的理化性质。花色苷磷脂复合物稳定性好。由于磷脂复合物具有类似磷脂的良好的粘膜透过性及缓慢释放特性，因此可增加花色苷在胃肠道中吸收，使花色苷具有一定长效作用。
具体实施方式
下面通过实施例对本发明做进一步详细说明，但本发明的保护范围不受实施例所限。
实施例1：
取黑米花色苷50mg，加入95％乙醇200ml，加入大豆磷脂100mg，加热至60℃回流并搅拌反应2小时，减压除去乙醇，常规低温真空干燥，得固体状花色苷磷脂复合物。
实施例2：
取越桔花色苷100mg，加入四氢呋喃500ml，加入大豆磷脂2000mg，加热至50℃回流，搅拌反应2小时，减压除去反应溶剂四氢呋喃，低温真空干燥，得固体状花色苷磷脂复合物。
所述的四氢呋喃可以由乙酸乙酯、丙醇或丁醇中的任意一种或它们的任意比例混合物替代。
实施例3：
取葡萄花色苷100mg，加入丙酮200ml，加入蛋黄磷脂1000mg，加热至60℃回流，搅拌反应1小时，减压除去反应溶剂丙酮，加入正己烷溶解，过滤，滤液减压回收溶剂正己烷，残渣低温真空干燥，得花色苷磷脂复合物。
实施例4：
取桑葚花色苷100mg，加入二氯甲烷300ml，加入蛋黄磷脂600mg，加热至40℃回流，搅拌反应2小时，减压除去反应溶剂，低温真空干燥，得花色苷磷脂复合物。
所述的蛋黄磷脂可以由大豆磷脂和蛋黄磷脂的任意比例混合物替代。
实施例5：
取山楂花色苷100mg，加入40％甲醇300ml，加入二棕榈酰磷脂酰胆碱(DPPC)1000mg，加热至60℃，搅拌反应2小时，减压除去反应溶剂，低温真空干燥，得花色苷磷脂复合物。
所述的山楂花色苷可以由黑米花色苷、桑葚花色苷和越桔花色苷的任意比例混合物替代。
实施例6：
取黑加仑花色苷100mg，加入正己烷50ml，加入二棕榈酰磷脂酰胆碱(DPPC)1000mg，加热至30℃，搅拌反应3小时，减压除去反应溶剂正己烷，低温真空干燥，得固体状花色苷磷脂复合物。
实施例7：
取越桔花色苷色素100mg，葡萄色素100mg，黑加仑色素100mg，加入无水乙醇600ml，加入合成磷脂二棕榈酰磷脂酰乙醇胺(DPPE)600mg，加热至60℃，搅拌反应1小时，减压除去反应溶剂无水乙醇，低温真空干燥，得固体状花色苷磷脂复合物。
实施例8：
取花青素葡萄糖苷(C3G)50mg，加入70％丙酮150ml，加入大豆卵磷脂1000mg，加热至50℃，搅拌反应1小时，减压除去反应溶剂丙酮，低温真空干燥，得固体状花青素磷脂复合物。
所述的70％丙酮可以由氯仿或乙醚替代。
所述的花青素葡萄糖苷可以由花青素半乳糖苷、花青素鼠李糖苷或花青素阿拉伯糖苷来替代。
实施例9：
取花青素半乳糖苷50mg，花青素鼠李糖苷50mg，花青素阿拉伯糖苷50mg，花青素葡萄糖苷50mg，加入70％丙酮200ml，加入大豆卵磷脂1000mg，加热至50℃，搅拌反应1小时，减压除去反应溶剂丙酮，低温真空干燥，得固体状花青素磷脂复合物。
所述的大豆卵磷脂可以由磷脂酰胆碱、磷脂酰乙醇胺或磷脂酰丝氨酸中的一种或它们的任意比例混合物来替代。
实施例10：
取实施例1中花色苷磷脂复合物及磷脂和花色苷及进行DSC分析，结果，花色苷磷脂复合物DSC谱图明显不同于磷脂和花色苷和它们物理混合物图谱，证明形成花青素磷脂复合物。在正辛醇中的溶解度是黑米色素的10倍。红外光谱中，黑米花色苷与磷脂复合物IR谱图明显不同于两者混合物，也不同于两者单独图谱。薄层色谱，展开剂为：乙酸乙酯∶乙酸∶2mol/L盐酸＝88∶7∶5，硅胶G薄层板，显色剂为盐酸或冰醋酸，展开显色后结果，黑米花色苷磷脂复合物显示斑点Rf值同黑米花色苷与磷脂斑点Rf值一致，证明磷脂复合物中含有磷脂和黑米色素。
实施例11：
用花色苷磷脂复合物(按实施例1方法制备)制备颗粒剂的处方组成为：
花色苷磷脂复合物20g，蔗糖粉100g，香精适量。
颗粒剂制备工艺过程为：将花色苷磷脂复合物与蔗糖粉混合均匀，用溶解香精的30％乙醇水制软材，并过20目筛制颗粒，于50℃通风干燥，得颗粒剂。
实施例12：
用花色苷磷脂复合物(按实施例1方法制备)制备片剂的处方组成为：
花色苷磷脂复合物200mg，可压性淀粉0.37g，硬脂酸镁10mg，交联PVP(PPVP)50mg，微粉硅胶10mg，羟丙基甲基纤维素适量。
片剂的制备工艺过程为：将花色苷磷脂复合物与可压性淀粉混合均匀后，用溶解HPMC的20％乙醇制软材，并过18目筛制颗粒，于50～C通风干燥，再用18目筛整粒，所得颗粒中加入PPVP、微粉硅胶、硬脂酸镁，混合均匀后压片，即得。
实施例13：
用花色苷磷脂复合物(按实施例1方法制备)制备硬胶囊剂的处方组成为：
花色苷磷脂复合物200g，淀粉150g，微晶纤维素50g，微粉硅胶10g。
胶囊剂的制备过程为：将复合物与淀粉、微晶纤维素、微粉硅胶混合均匀后装硬胶囊剂，即得。
实施例14：
用花色苷磷脂复合物(按实施例4方法制备)制备软胶囊剂的处方组成为：
花色苷磷脂复合物20g，油酸乙酯100g，大豆油100g。
软胶囊的制备过程为：将复合物溶于油酸乙脂和大豆油的混合液中，得一透明药液：取明胶、甘油、山梨醇、水配制明胶溶液，置铺展箱中备用。在室温23±2℃、相对湿度40％的条件下用滴制法制成胶丸，且在23±2℃、相对湿度40％的条件下冷风干燥24小时即得。
实施例15：
花色苷磷脂复合物乳化剂的制备工艺如下：
取按照实施例7方法制得的花色苷磷脂复合物1g，大豆油10g，卵磷脂1.5g，油酸0.5g，甘油2g，，注射用水适量，合计100g。采用高剪切机制备初乳，然后采用高压均质机以80兆帕循环5次，以0.45μm滤膜过滤，灌装得到乳剂。
实施例16：
花色苷磷脂复合物的脂质纳米粒的制备工艺如下：
取实施例4制得的花色苷磷脂复合物1g，山嵛酸甘油脂5g，中链油1g，卵磷脂1.5g，伯洛沙姆0.5g，吐温(80)0.5g，，注射用水适量，合计100g。将上述配料加热至70℃，剪切5分钟，然后在高压均质机中以100兆帕压力循环5次，放冷至室温，灌装即得。
实施例17：
稳定性试验：取按实施例1方法制备的花色苷磷脂复合物和同批次黑米花色苷原料，按照光照影响因素试验做稳定性考察。
光照影响因素试验，取上述样品各10g分成若干份，置于4500LX灯箱中，分别与0时，6时，12时，24时，3天，5天，10天取样测定吸光度下降率结果见表1。
表1光照(4500LX)对叶黄素微囊稳定性影响：
结果证明，磷脂复合物光稳定性好。
实施例18.
生物吸收代谢研究
实验动物：SD大鼠，雌雄各半。
实验药物：黑米色素(含花青素葡萄糖苷75％)，按照实施例1方法制备的花色苷磷脂复合物(含C3G 30％)。
实验方法：将大鼠12只，随机分成2组，每组6只。给药前禁食12小时，自用饮水。第一组：黑米色素(含花青素葡萄糖苷C3G 75％)，给药浓度为1mmol/kg；第二组：花色苷磷脂复合物组，给药浓度为2mmol/kg。各组动物给药后，不同时间点在大鼠眼眶底静脉丛采血，置肝素化的试管内，分离血浆，采用液相-串联质谱法测定C3G含量。结果，在给药20分钟后黑米色素组血浆样品即有微量C3G成分检出，黑米色素磷脂复合物(含C3G 30％)组样品峰面积明显大于黑米色素组。但在1小时后黑米色素组血浆样品没有检出C3G成分，而黑米色素磷脂复合物(含C3G 30％)组样品在6小时后仍可检出。本试验提示黑米花色苷磷脂复合物具有比原型药物更好的吸收和长效性。
Claims (10)
1、一种花色苷磷脂复合物，其特征在于其组成包括花色苷与磷脂，花色苷与磷脂的重量比为1∶1-20。
2、根据权利要求1所述的花色苷磷脂复合物，其特征在于其组成包括花色苷与磷脂，花色苷与磷脂的重量比为1∶2-4。
3、根据权利要求1或2所述的花色苷磷脂复合物，其特征在于所述的花色苷是葡萄花色苷、黑米花色苷，越桔花色苷，黑加仑花色苷、山楂花色苷或桑葚花色苷中的一种或它们的任意比例混合物。
4、根据权利要求1或2所述的花色苷磷脂复合物，其特征在于所述的花色苷是花青素鼠李糖苷、花青素半乳糖苷、花青素阿拉伯糖苷或花青素葡萄糖苷中的一种或它们的任意比例混合物。
5、根据权利要求1或2所述的花色苷磷脂复合物，其特征在于所述的磷脂是大豆磷脂、蛋黄磷脂或大豆磷脂和蛋黄磷脂或它们的混合物；磷脂是磷脂酰胆碱、磷脂酰乙醇胺或磷脂酰丝氨酸中的至少一种；磷脂也可以是二棕榈酰磷脂酰胆碱、二棕榈酰磷脂酰乙醇胺或二棕榈酰磷脂酰胆碱和二棕榈酰磷脂酰乙醇胺的混合物。
6、一种权利要求1或2所述的花色苷磷脂复合物的制备方法，其特征在于它包括如下步骤：按所述重量比取花色苷与磷脂，于介电常数小的有机溶剂中混合，有机溶剂的使用量为1毫克花色苷不低于1ml的有机溶剂，反应的温度为10-80℃，反应时间为0.5-5小时，然后减压干燥或冷冻干燥，除去有机溶剂，得花色苷磷脂复合物。
7、根据权利要求6所述的花色苷磷脂复合物制备方法，其特征在于所述的有机溶剂为氯仿、乙醚、丙酮、二氯甲烷、四氢呋喃、乙酸乙酯、正己烷、C1-C6直链或支链低级烷醇中的一种或一种以上混合物，其中C1-C6直链或支链低级烷醇为甲醇、乙醇、丙醇或丁醇。
8、根据权利要求6所述的花色苷磷脂复合物制备方法，其特征在于所述的花色苷磷脂复合物加入常规辅料按常规方法制成颗粒剂、胶囊剂或片剂。
9、根据权利要求6所述的花色苷磷脂复合物制备方法，其特征在于所述的花色苷磷脂复合物加入乳化剂和中链脂肪酸液体油或植物油，经乳化后制成花色苷磷脂复合物脂肪乳剂。
10、根据权利要求6所述的花色苷磷脂复合物制备方法，其特征在于所述的花色苷磷脂复合物加入乳化剂和固体脂质、液体脂质或他们的混合物，制成脂质纳米粒。
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| CN102688501A (zh) * | 2012-06-20 | 2012-09-26 | 浙江萧山医院 | 原花青素b2磷脂复合物及其制备方法和用途 |
| CN103120798A (zh) * | 2013-01-10 | 2013-05-29 | 施冬云 | 一种具有抗氧化应激作用的磷脂复合物制备方法及其应用 |
| CN104082432A (zh) * | 2014-06-13 | 2014-10-08 | 宁波大学 | 一种含有紫薯花色苷抗氧化大豆油的制备方法 |
| CN104640461A (zh) * | 2012-08-09 | 2015-05-20 | 雀巢产品技术援助有限公司 | 花色素苷着色组合物 |
| CN105614764A (zh) * | 2015-12-29 | 2016-06-01 | 广东省农业科学院蚕业与农产品加工研究所 | 一种桑椹纳米微胶囊的制备方法及由其组成的营养粉 |
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| CN1799542A (zh) * | 2004-12-30 | 2006-07-12 | 天津中新药业集团股份有限公司 | 山楂总黄酮磷脂复合物及其制备方法 |
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