CN103211806B - 新颖的营养药物性组合物及其用途 - Google Patents
新颖的营养药物性组合物及其用途 Download PDFInfo
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- CN103211806B CN103211806B CN201310081874.XA CN201310081874A CN103211806B CN 103211806 B CN103211806 B CN 103211806B CN 201310081874 A CN201310081874 A CN 201310081874A CN 103211806 B CN103211806 B CN 103211806B
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Abstract
本发明提供了新颖的营养药物性组合物及其用途。本发明公开了一种组合物,其中包含作为活性成份的白藜芦醇、其衍生物、代谢物或类似物和至少一种选自EGCG、染料木黄酮、维生素E、多不饱和脂肪酸、gamma-亚麻酸和维生素K的额外成分。该组合物具有抗炎症作用,其可以是食物或饮料或其添加剂;或者可以是药物组合物。
Description
本发明是基于中国专利申请号201110049385.7的分案申请。
本发明涉及新颖的营养药物性组合物,其包含作为活性成份的白藜芦醇、其衍生物、代谢物或类似物和至少一种选自EGCG、染料木黄酮、维生素E、多不饱和脂肪酸、gamma-亚麻酸和维生素K的额外成分。
本文中使用的术语“营养药物性(nutraceutical)”表示了同时在营养领域及医药领域应用中的有效性。因此,新颖的营养药物性组合物可作为食物和饮料的添加剂,也可作为药物制剂用于肠道或非肠道应用,所述药物制剂可以是固体制剂,例如胶囊或药片,或是液体制剂,例如溶液或悬浮液。从前文明显可知,术语“营养药物性组合物”也包括含有上面指明的活性成份的食物和饮料。
本文中使用的术语“白藜芦醇、其衍生物、代谢物或类似物”包含:如下结构通式所包括的化合物
其中,A表示碳-碳双键,其可以是顺式的或反式的,R1、R2、R3、R4、R5和R6各自独立地表示氢、羟基或经醚化或酯化的羟基。虽然符号A所指代的碳-碳双键可以是顺式的或反式的,但上述结构式I应被理解为还包括顺式/反式混合物。然而,其中A是反式碳-碳双键的结构式I所示的化合物是优选的。
经醚化或酯化的羟基可以来自未被取代的或被取代的、直链或带有支链的、具有1至26个碳原子的烷基,或来自未被取代的或被取代的、直链或带有支链的、具有1至26个碳原子的脂肪族、芳烷族(araliphatic)或芳香族羧酸。经醚化的羟基进一步地可以是糖苷基团,经酯化的羟基进一步地可以是葡糖苷酸或硫酸酯基团。如结构式I所示的化合物的例子是白藜芦醇(Resveratrol,R1、R3和R5=氢,R2、R4和R6=羟基);四羟反式芪(Piceatannol)(R3和R5=氢,R1、R2、R4和R6=羟基)以及丹叶大黄素(Rhapontigenin)(R5=氢,R1、R3、R4和R6=羟基,R2=甲氧基)。本发明最基本的兴趣是针对(反式)白藜芦醇的。
本文中使用的术语“EGCG”包括(-)-表没食子儿茶素没食子酸酯((-)-Epigallocatechin gallate)和/或其一种或多种衍生物(经酯化的形式、糖苷、硫酸酯)。
本文中使用的术语“多不饱和脂肪酸”(本文中业称为PUFA)指经酯化的(例如,作为甘油三酯或乙酯)或以游离形式存在的多不饱和脂肪酸,特别是,omega-3多不饱和脂肪酸,例如二十碳五烯酸(5,8,11,14,17-二十碳五烯酸,EPA)和二十二碳六烯酸(4,7,10,13,16,19-二十二碳六烯酸,DHA),或者omega-6-多不饱和脂肪酸,例如γ-亚麻酸(6,9,12-十八碳三烯酸,GLA)。
本文中使用的术语“维生素K”包含叶绿醌(维生素K1),以及具有类似于维生素K1的生理活性的萘醌醇(naphthoquinol)或萘醌,特别是,维生素K2和K3。
本文中使用的术语“维生素E”是基于6-色原烷醇(6-chromal)的一组化合物,其包括外消旋维生素E(D,L-α-生育酚)或天然维生素E,以及具有维生素E生物活性的其衍生物,例如其它生育酚或生育三烯酚(tocotrienol)或羧酸酯,例如乙酸、丙酸、丁酸或琥珀酸维生素E酯。
本文中使用的术语“染料木黄酮”包括苷元(4’,5,7-三羟基异黄酮)及其衍生物,例如染料木黄酮糖苷、染料木黄酮硫酸酯、染料木黄酮葡糖苷酸。
本发明组合物的活性成份具有不同的作用机制,因而能在对上文指明的疾病的预防或治疗中提供协同作用,尤其是炎症性疾病。
炎症性疾病是全世界最重要的健康问题之一。炎症通常是体内组织对于外界物质或有害刺激入侵宿主时产生的局部保护应答。致炎症的因素是感染源,例如细菌、病毒和寄生虫;物理因素,例如灼伤或辐射;化学物质,例如毒素、药物或干业试剂;以及免疫反应,例如过敏或自身免疫应答。
两类主要的药物,皮质类固醇(cortiocosteroid)和非固醇类抗炎药(NSAID)被用于治疗炎症性疾病。NSAID和皮质类固醇主要提供对症状的缓解。对皮质类固醇的使用已减少,因为人们对其长时期使用的副作用的担忧加剧。NSAID属于最广泛使用的药物,主要用于治疗疼痛和炎症,尤其是关节炎。但是,对上述药物的长期使用都受其严重的副作用所限,例如严重的胃肠道并发症、肾脏毒性或哮喘反应。因此,人们需要一种新型的、具有较弱副作用或没有副作用的抗炎试剂。考虑到炎症性疾病,特别是风湿性紊乱的重要性,人们需要适合用于治疗非急性风湿症的抗炎植物化学制剂。患有炎症性疾病的病人对于具有温和抗炎作用而没有较大副作用的被认为是“天然的”治疗有着特别的兴趣,这种治疗可用作疾病预防或辅助治疗。
炎症的特征在于疼痛、红肿、发热以及受影响区域最终的功能丧失。上述症状是免疫系统细胞间发生的一系列复杂相互作用的结果。细胞的反应使得三族主要的炎症介质间产生相互作用的网络:蛋白质(例如细胞因子、酶(例如蛋白酶、过氧化物酶)、主要的基础蛋白质(MPC)、粘附分子(ICAM、VCAM),脂类介质(例如,类二十烷、前列腺素、白细胞三烯、血小板激活因子(PAF)),活性氧类(例如,过氧化氢、超氧化物阴离子O2 -、一氧化氮(NO))。但是,上述炎症介质中的很多也是正常细胞活性的调节者。因此,炎症反应的缺乏将导致宿主受到威胁(即感染),而过度的发炎又会导致若干种由上述介质过量产生所部分介导的炎症性疾病。对其治疗需要维持过量和不足的炎症反应之间的平衡。具有轻微抗炎活性而作用机制又有所不同的天然产物例如白藜芦醇与EGCG、染料木黄酮、维生素E、omega-3PUFA(例如,二十碳五烯酸、二十二碳六烯酸)、琉璃苣油(gamma-麻酸)、维生素K之间的组合,非常有利于保持这样的平衡。
由于炎症介质生物合成过度造成的急性及慢性炎症与数种疾病相关,例如关节炎(例如骨关节炎、风湿关节炎)、哮喘、炎症性肠道疾病、炎症性皮肤病(例如,牛皮癣、过敏性皮炎)和其它具有炎症性质的慢性疾病,例如动脉硬化、心脏病、糖尿病、代谢综合征X、癌症、Alzheimer’s病及其早期症状,例如轻微的认知受损。
风湿关节炎是慢性的关节炎症性疾病。其特征在于滑膜发炎以及嗜中性粒细胞、巨噬细胞和淋巴细胞渗入关节。随着病程发展,炎症导致滑膜增生,对关节软骨及软骨下面的骨头产生损害,以及随后导致关节变形和功能丧失。哮喘和风湿关节炎分子水平上的特征在于:细胞因子(cytokines)、趋化因子(chemokines)、激肽及其受体、粘附分子以及炎症性酶(例如诱导型一氧化氮合成酶(iNOS)和诱导型环氧化酶(COX-2))的长期不平衡表达。前炎症细胞因子在骨关节炎的发展中还扮演着重要的角色。牛皮癣是最常见的皮肤问题之一,其影响1-3%的人口。炎症性肠道疾病是用于描述溃疡性结肠炎或Crohn’s病的通用术语。
动脉硬化目前被认为是血管壁的炎症性疾病,而非简单的血管内脂类堆积的过程。动脉硬化由血管受损后的炎症所导致。动脉硬化斑块中存在有被激活的巨噬细胞、T-淋巴细胞和肥大细胞。单核细胞和淋巴细胞的激活导致类二十烷和细胞因子的释放,其与内皮细胞受损,以及动脉硬化斑块的形成和最终破裂相关。最后,循环炎症标志,例如C反应蛋白(CRP)、纤维蛋白原以及白细胞介素成批增长,冠心病风险变高。若干项临床试验表明,CRP浓度增高与冠心病和血管问题风险增加相关。因此炎症看起来在动脉粥样化形成的起始和发展过程中都扮演了重要的角色。此外,2型糖尿病和肥胖是冠心病和动脉硬化发展的风险因子。上述情况与胰岛素抵抗、氧化胁迫和炎症相关。对动物模型和人进行的大量研究表明,炎症、对胰岛素不敏感性以及脂类代谢紊乱是有联系的。炎症介质,例如血浆白细胞介素6(IL-6)、肿瘤坏死因子alpha(TNF-α)和CRP在2型糖尿病和肥胖中都有增加。脂肪组织可以合成细胞因子,例如TNF-α和IL-6,它们能导致肥胖患者的炎症。因此,抗炎试剂可以在对动脉硬化、糖尿病和肥胖的预防和治疗中发挥作用。
流行病学研究表明,服用非固醇类抗炎药(NSAID)的人群,较之不服用NSAID的人群,结肠、直肠、胃、食道和乳腺癌的风险显著降低。在动物模型中,NSAID显著地减少了肿瘤的发展。在人类的乳腺、结肠、肺和胰腺癌中都已发现前列腺素的水平增加。此外,COX-2,也在一系列肿瘤中过量表达。因此,COX抑制剂可能可以用于癌症预防和治疗。
炎症情况还可能与Alzheimer’s病的病理相关。在Alzheimer’s病患者的肭部发现了炎症的证据。其特征在于细胞因子水平增高以及胶质因子被激活。流行病学研究已经表明,较之未服用NSAID的病人,服用NSAID的病人Alzheimer’s病的发展风险较低。NSAID的保护性作用暗示,环氧化酶可能与神经退行性疾病相关。因此,炎症介质的过量产生受到抑制,可以预防和/或减缓Alzheimer’s病的病程。
因此,炎症不仅仅与经典的炎症性疾病(例如,关节炎、哮喘、肠道疾病)相关,其还与很多慢性病(例如,动脉硬化、心脏病、糖尿病、代谢综合征X、癌症、Alzheimer病)相关。
包含活性成份,即白藜芦醇或衍生物和至少一种选自EGCG、染料木黄酮、维生素E、omega-3PUFA(二十碳五烯酸、二十二碳六烯酸)、琉璃苣油(gamma-麻酸)和维生素K的额外成分的组合物,对治疗或预防具有炎症情况的疾病是特别有用的。此外,复合维生素和矿物质添加剂可以加入到本发明的营养药物性组合物中,以获得足够量的必要营养成分,其是某些膳食中所缺乏的。复合维生素和矿物质添加剂还可以用于预防或治疗由生活方式导致的营养缺乏及缺陷等疾病。
本发明的营养药物性组合物含有的白藜芦醇的量足以以约0.5mg/天至约2000mg/天的剂量施予成年人类(体重约70kg),优选为约5mg/天至约500mg/天。因此,在所述营养约物性组合物是食物或饮料的情况下,其中含有的白藜芦醇的量适合在每份(serving)约0.2mg至每份约500mg的范围内。如果所述营养药物性组合物是药物制剂,那么此类制剂的每个固体剂量单位(例如每一药片或胶囊)中,可以含有约0.5mg至约500mg,或者在液体制剂中含有约0.5mg的每日剂量至约2000mg的每日剂量。
优选地,EGCG的使用浓度使得成年人类(体重约70kg)的每日消耗在10mg/天至2000mg/天之间。每份食物或饮料适合含有大约2mg至大约500mg的EGCG。如果所述营养药物性组合物是药物制剂,那么此类制剂的每个固体剂量单位(例如每一药片或胶囊)中,可以含有约5mg至约500mg的EGCG,或者在液体制剂中含有约10mg的每日剂量至约2000mg的每日剂量。
优选地,PUFA的使用浓度使得成年人类(体重约70的每日消耗在10mg/天至4000mg/天之间。每份食物或饮料适合含有大约5mg至大约1000mg的PUFA。如果所述营养药物性组合物是药物制剂,那么此类制剂的每个固体剂量单位(例如每一药片或胶囊)中,可以含有约10mg至约1000mg的PUFA,或者在液体制剂中含有约10mg的每日剂量至约4000mg的每日剂量。
优选地,染料木黄酮的使用浓度使得成年人类(体重约70kg)的每日消耗在0.5mg/天至2000mg/天之间。每份食物或饮料适合含有大约0.5mg至大约500mg的染料木黄酮。如果所述营养药物性组合物是药物制剂,那么此类制剂的每个固体剂量单位(例如每一药片或胶囊)中,可以含有约0.5mg至约500mg的染料木黄酮,或者在液体制剂中含有约0.5mg的每日剂量至约2000mg的每日剂量。
优选地,维生素E或其衍生物的使用浓度使得成年人类(体重约70kg)的每日消耗在5mg/天至2000mg/天之间。每份食物或饮料适合含有大约2mg至大约500mg的维生素E。如果所述营养药物性组合物是药物制剂,那么此类制剂的每个固体剂量单位(例如每一药片或胶囊)中,可以含有约5mg至约1000mg的维生素E,或者在液体制剂中含有约5mg的每日剂量至约2000mg的每日剂量。
优选地,维生素K的使用浓度使得成年人类(体重约70的每日消耗在10μg/天至50mg/天之间。每份食物或饮料适合含有大约2μg至大约20mg的维生素K。如果所述营养药物性组合物是药物制剂,那么此类制剂的每个固体剂量单位(例如每一药片或胶囊)中,可以含有约10μg至约25mg的维生素K,或者在液体制剂中含有约10μg的每日剂量至约50mg的每日剂量。
本文中使用的术语“份(serving)”表示一定量的食物或饮料,其通常作为一餐被成年人一次性正常消化,其范围例如可以是大约100g至大约500g。
在本发明的一个方面,组合物可用作为营养添加剂,例如,作为复合维生素制剂的添加剂,所述制剂包含维持正常代谢功能所必需的、却无法在体内合成的维生素和矿物质,特别是用于治疗或预防炎症性疾病的。
根据本发明的另一方面,组合物可以是药物组合物,优选是肠道应用的,其可以是固体或液体的盖仑(galenical)制剂。固体盖仑制剂的例子是药片、胶囊(例如硬或软壳的明胶胶囊)、药丸、药袋(sachet)、粉末、颗粒等,其中含有活性成份以及传统的盖仑载体。任何传统的载体材料都可使用。载体材料可以是适于口服的有机或无机惰性载体材料。合适的载体包括水、明胶、阿拉伯胶、乳糖、淀粉、硬脂酸镁、滑石粉、植物油等。此外,添加剂,例如香味剂、防腐剂、稳定剂、乳化剂、缓冲剂等,可以按照可被接受的药物组合形式来加入。当个别活性成份适于以单一组合物的形式服用的时候,它们还可以以单独的剂量形式被服用。
本发明的组合物中,活性成份的特定组合包括:
白藜芦醇和EGCG;
白藜芦醇和维生素E;
白藜芦醇和PUFA(EPA;DHA;GLA);
白藜芦醇、维生素E、EGCG;
白藜芦醇、维生素K、EGCG;
白藜芦醇、维生素E、PUFA(EPA;DHA;GLA);
白藜芦醇、EGCG、维生素E和PUFA(EPA;DHA;GLA);
白藜芦醇、维生素E、PUFA(EPA;DHA;GLA)、染料木黄酮;
白藜芦醇、EGCG、维生素E、染料木黄酮、PUFA(EPA;DHA;GLA);
最优选的是有或没有维生素E的白藜芦醇、EGCG、PUFA(EPA;DHA;GLA)的组合;以及白藜芦醇、EGCG、维生素E、染料木黄酮、PUFA(EPA;DHA;GLA)的组合。
为确定化合物或其组合的抗炎症性质,在所述化合物存在的情况下,体外用炎症激发物对合适的细胞或细胞系(例如,全血、巨噬细胞、白细胞)进行激活。这会导致前列腺素(即,环氧化酶-2的产物)和一氧化氮(由诱导型一氧化氮合成酶合成)的分泌。由于化合物的抗炎症效果,它们将会降低这两种代谢产物的水平。类似地,用定量PCR或微芯片分析(micro-array analysis)技术对炎症途径的基因表达进行监测。抗炎症化合物能降低它们的表达水平。化合物的加合和/或协同效应将在特定的炎症参数的水平上,以及更为普遍的与细胞炎症应答相关的基因表达的水平上被鉴定出来。
通过测定对一氧化氮和/或PGE2合成的抑制,在被激活的巨噬细胞中可以显示出白藜芦醇和EGCG或EPA的组合疗法的抗炎症效果。
为诱导体外“炎症应答”,将鼠科动物巨噬细胞RAW264.7接种入微滴定板或12孔板中,用脂多糖(LPS)对其进行激活,其中测试物质可以存在或不存在梯度数量。媒介(vehicle)浓度(即DMSO)保持恒定。合适的时间段(4至24小时)后,收集培养物上清液。通过ELISA和Griess反应,对分泌到培养基中的前列腺素E2(PGE2)和一氧化氮(NO)生成的亚硝酸盐分别进行定量。对给定浓度的测试物质而言,计算对PGE2或NO生产的抑制百分比(较之LPS激活的细胞的最大产量)。
结果被展示于下表1和2中:
表1:LPS激活的巨噬细胞中,白藜芦醇和EGCG对NO和PGE2生产的作用
表2:LPS激活的巨噬细胞中,白藜芦醇和EPA对NO生产的作用
用白藜芦醇和EGCG的组合治疗对巨噬细胞中NO和PGE2的生产施加了协同作用(表1)。白藜芦醇和二十碳五烯酸(EPA)对被激活的巨噬细胞中NO的生产也有协同作用(表2)。因此,表1和表2的数据显示,白藜芦醇和EGCG以及白藜芦醇和EPA的组合对炎症应答的减轻有协同作用。
下述实施例将更进一步地阐述本发明。
A.可以用下列组分按照传统配制工序来制备药物组合物:
实施例1软明胶胶囊
使用下列组分按照传统工序来制备软明胶胶囊:
活性成份:白藜芦醇10mg、EPA200mg、维生素E50mg
其它组分:甘油、水、明胶、植物油
实施例2硬明胶胶囊
使用下列组分按照传统工序来制备硬明胶胶囊:
活性成份:白藜芦醇10mg、EGCG100mg、染料木黄酮5mg、维生素E50mg、维生素K1mg
其它组分:填料:数量足够的乳糖或纤维素或纤维素衍生物
润滑剂:如果需要的话,硬脂酸镁(0.5%)
实施例3药片
使用下列组分按照传统工序来制备约片:
活性成份:白藜芦醇5mg、EGCG50mg、维生素E20mg
其它组分:微晶纤维素、二氧化硅(SiO2)、硬脂酸镁、交联羧甲基纤维素钠。
B.可以使用下列组分按照传统工序来制备食物产品:
实施例4含30%果汁的软饮
活性成份:该食物产品中加入了白藜芦醇,以及一种或多种选自EGCG、PUFA(EPA、DHA、GLA)、染料木黄酮、维生素E和维生素K的额外成分。
白藜芦醇:每份0.2mg-200mg
EGCG:每份2mg-200mg
PUFA(EPA、DHA、GLA):每份5mg-500mg
染料木黄酮:每份0.2mg-50mg
维生素E:每份5mg-100mg
维生素K:每份0.01mg-5mg
典型份量:240ml
I.用下述组分制备软饮复合物:
果汁浓缩物和水溶性香料
1.2颜料 [g]
β-胡萝卜素10%CWS 0.89
水 67.65
1.3酸和抗氧化剂
抗坏血酸 4.11
无水柠檬酸 0.69
水 43.18
1.4稳定剂
果胶 0.20
苯甲酸钠 2.74
水 65.60
1.5油溶性香料
油溶性橙味香料 0.34
蒸馏得到的甜橙油 0.34
1.6活性成份
以上文提到的浓度存在的活性成份(这指上文提到的活性成份:白藜芦醇以及以下物质中的一种或多种:EGCG、PUFA(EPA、DHA、GLA)、染料木黄酮、维生素E和维生素K)。
果汁浓缩物和水溶性香料在没有空气掺入的条件下混合起来。颜料被溶于去离子水中。抗坏血酸和柠檬酸溶于水中。苯甲酸钠溶于水中。搅拌下加入果胶,煮沸令其溶解。冷却所述溶液。油溶性香料和甜橙油预先混合起来。1.6中提到的活性成份被干燥地混合起来,然后优选搅拌添加到果汁浓缩物混合物(1.1)中。
为制备所述的软饮复合物,3.1.1至3.1.6的所有部分都被混合到一起,然后用Turrax再用高压均质机(p1=200bar,p2=50bar)对其进行均质。
II.用下述组分来制备瓶装糖浆:
所述瓶装糖浆的组分被混合到一起。用水将所述瓶装糖浆稀释到1L,成为现成可用的饮料。
变化:
可以对所述饮料进行巴氏消毒来代替使用苯甲酸钠。所述饮料还可经过碳酸化。
实施例5五谷面包
活性成份:该食物产品中加入了白藜芦醇,以及一种或多种选自EGCG、PUFA(EPA、DHA、GLA)、染料木黄酮、维生素E和维生素K的额外成分。
白藜芦醇:每份0.2mg-100mg
EGCG:每份2mg-100mg
PUFA(EPA、DHA、GLA):每份5mg-200mg
染料木黄酮:每份0.2mg-20mg
维生素E:每份5mg-100mg
维生素K:每份0.01mg-5mg
典型份量:50g
所述酵母被溶于一部分水中。将所有组分混合到一起制成面团。在揉捏过程结束时加盐。发酵之后,对面团进行再次处理,并将其分开,然后制成块状。烘焙之前,用水冲刷所述的块表面,并撒上面粉。
工艺参数:
揉捏:
螺旋揉捏系统: 第一档4分钟,第二档5分钟
面团发酵: 60分钟
面团温度: 22℃-24℃
发酵时间 30分钟
烘焙:
烤箱: 荷兰式烤箱
烘焙温度: 250℃/220℃
烘焙时间: 50-60分钟
实施例6Milano类型的曲奇饼
活性成份:该食物产品中加入了白藜芦醇,以及一种或多种选自EGCG、PUFA(EPA、DHA、GLA)、染料木黄酮、维生素E和维生素K的额外成分。
白藜芦醇:每份0.2mg-100mg
EGCG:每份2mg-100mg
PUFA(EPA、DHA、GLA):每份5mg-200mg
染料木黄酮:每份0.2mg-20mg
维生素E:每份5mg-100mg
维生素K:每份0.01mg-5mg
典型份量:30g
在搅拌条件下将所有组分缓慢加入,制成甜酥点心团(sweet shortpastry)。
之后,将所述点心团冷藏(4℃)至少2小时,之后将其抹平成厚度为大约5mm。烘焙前切成小块,在表面刷上蛋黄。
烘焙:
烤箱: 鼓风式烤箱(fan oven)
烘焙温度: 180℃
烘焙时间: 15分钟
实施例7吐司面包
活性成份:该食物产品中加入了白藜芦醇,以及一种或多种选自EGCG、PUFA(EPA、DHA、GLA)、染料木黄酮、维生素E和维生素K的额外成分。
白藜芦醇:每份0.2mg-100mg
EGCG:每份2mg-100mg
PUFA(EPA、DHA、GLA):每份5mg-200mg
染料木黄酮:每份0.2mg-20mg
维生素E:每份5mg-100mg
维生素K:每份0.01mg-5mg
典型份量:100g
所述酵母被溶于一部分水中。所有组分被混合到一起,形成面团。在揉捏过程结束时加入盐。之后,对所述面团进行再次处理,将其分开,放置于烘焙用烤模上以发酵。烘焙之后,所述的块直接从模子里取出。
工艺参数:
揉捏:
螺旋揉捏系统: 第一档5-6分钟,第二档3-4分钟
面团发酵: 无
面团温度: 22℃-24℃
发酵时间 40分钟
烘焙:
烤箱: 荷兰式烤箱
烘焙温度: 220℃
烘焙时间: 35-40分钟
实施例8酸奶-凝固型(Yoghurt set type),3.5%的脂肪
活性成份:该食物产品中加入了白藜芦醇,以及一种或多种选自EGCG、PUFA(EPA、DHA、GLA)、染料木黄酮、维生素E和维生素K的额外成分。
白藜芦醇:每份0.2mg-100mg
EGCG:每份2mg-100mg
PUFA(EPA、DHA、GLA):每份5mg-200mg
染料木黄酮:每份0.2mg-20mg
维生素E:每份5mg-100mg
维生素K:每份0.01mg-5mg
典型份量:225g
所述的奶被加热至35℃,然后加入奶粉、稳定剂、糖和活性成份。该混合物被加热至65℃以溶解所有组分。然后在高压均质机中(p1=150bar,p2=50bar)于65℃下对所述混合物进行均质。再在80℃下对该乳状物进行20分钟的巴氏消毒。冷却到45℃后,加入天然酸奶/培养物,混匀。再将该混合物装入若干杯子,在45℃下发酵3-4小时,直到pH达到4.3,然后将其贮藏在4℃下。
实施例9酸奶-搅拌型,3.5%的脂肪
活性成份:该食物产品中加入了白藜芦醇,以及一种或多种选自EGCG、PUFA(EPA、DHA、GLA)、染料木黄酮、维生素E和维生素K的额外成分。
白藜芦醇:每份0.2mg-100mg
EGCG:每份2mg-100mg
PUFA(EPA、DHA、GLA):每份5mg-200mg
染料木黄酮:每份0.2mg-20mg
维生素E:每份5mg-100mg
维生素K:每份0.01mg-5mg
典型份量:225g
所述的奶被加热至35℃,然后加入奶粉、稳定剂、糖和活性成份。该混合物被加热至65℃以溶解所有组分,然后在高压均质机中(p1=150bar,p2=50bar)于65℃下对所述混合物进行均质。再在80℃下对该乳状物进行20分钟的巴氏消毒。冷却到45℃后,加入天然酸奶/培养物,混匀,接着在45℃下发酵3-4小时,直到pH达到4.3。经过冷却及有力的搅拌之后,所述酸奶被装进若干杯子,在4℃贮藏。
实施例10冰淇淋,8%的脂肪
活性成份:该食物产品中加入了白藜芦醇,以及一种或多种选自EGCG、PUFA(EPA、DHA、GLA)、染料木黄酮、维生素E和维生素K的额外成分。
白藜芦醇:每份0.2mg-100mg
EGCG:每份2mg-100mg
PUFA(EPA、DHA、GLA):每份5mg-200mg
染料木黄酮:每份0.2mg-20mg
维生素E:每份5mg-100mg
维生素K:每份0.01mg-5mg
典型份量:85g
将糖、脱脂奶粉和稳定剂加入到奶和鲜奶油中,混匀,加热至45℃。然后将活性成份以及葡萄糖浆和贮存液形式的颜料加进去。该混合物被加热进行巴氏消毒(80℃,20分钟)。然后进行均质步骤。之后,该混合物在持续搅拌下被冷却,在5℃下加入香料。将该混合物在5℃下成熟至少4小时,再通过冰淇淋机(膨胀率约为100%)。所述冰淇淋被装入若干杯子,贮藏于-20℃至-30℃。
实施例11酒胶糖(winegum)
活性成份:该食物产品中加入了白藜芦醇,以及一种或多种选自EGCG、PUFA(EPA、DHA、GLA)、染料木黄酮、维生素E和维生素K的额外成分。
白藜芦醇:每份0.2mg-50mg
EGCG:每份2mg-50mg
PUFA(EPA、DHA、GLA):每份5mg-100mg
染料木黄酮:每份0.2mg-10mg
维生素E:每份5mg-10mg
维生素K:每份0.01mg-5mg
典型份量:30g
将明胶分散于水I中,搅拌,通过蒸气浴加热或使用微波炉令其溶解。将糖和水II混合,煮沸直到获得澄清溶液。从热源上移开。趁着溶解有糖的溶液还是热的,将其与糖浆混合。缓慢加入明胶溶液。保持静置,直至表面泡沫能被除去,并达到60℃-65℃。在搅拌下加入香料、柠檬酸和颜料溶液以及活性成份。将其倒入淀粉盘(starch tray)上印制的模子中,在室温放置至少48小时。移走淀粉粉末,用油或蜡抛光。在室温干燥并装入密封小袋中。
Claims (20)
1.通过抑制NO的生产用于治疗或预防炎症性疾病的组合物,其中的唯一活性成份由白藜芦醇和omega-3多不饱和脂肪酸组成。
2.如权利要求1所述的组合物,其中所述omega-3多不饱和脂肪酸是EPA或DHA。
3.如权利要求1所述的组合物,其中所述omega-3多不饱和脂肪酸是EPA。
4.如权利要求1所述的组合物,其为药物组合物并且是固体盖仑制剂,其含有活性成分以及盖仑载体。
5.如权利要求1至4中任意一项所述的组合物,其中含有的白藜芦醇的量足以给予成年人0.5mg至2000mg的每日剂量。
6.如权利要求1至4中任意一项所述的组合物,其中含有的多不饱和脂肪酸的量足以给予成年人10mg至4000mg的每日剂量。
7.如权利要求1所述的组合物,其为剂量单位形式。
8.如权利要求7所述的组合物,其中,所述剂量单位形式是固体剂量单位形式。
9.如权利要求8所述的组合物,其中所述的剂量单位形式中含有0.5mg至500mg的白藜芦醇。
10.如权利要求8或9所述的组合物,其中所述的剂量单位形式中含有10mg至1000mg的多不饱和脂肪酸。
11.如权利要求1所述的组合物,其中所述组合物是食物或饮料,或用于食物或饮料的添加剂组合物。
12.根据权利要求1所述的组合物在制造通过抑制NO的生产用于治疗或预防炎症性疾病的药物中的用途。
13.根据权利要求1所述的组合物在制造通过抑制NO的生产用于治疗或预防炎症性疾病的营养药物性产品中的用途。
14.如权利要求12或13所述的用途,其为药物组合物并且是固体盖仑制剂,其含有活性成分以及盖仑载体。
15.如权利要求12或13所述的用途,其中所述组合物中含有的白藜芦醇的量足以给予成年人0.5mg至2000mg的每日剂量。
16.如权利要求12或13所述的用途,其中所述组合物中含有的多不饱和脂肪酸的量足以给予成年人10mg至4000mg的每日剂量。
17.如权利要求12或13所述的用途,其中所述组合物为剂量单位形式。
18.如权利要求17所述的用途,其中,所述剂量单位形式是固体剂量单位形式。
19.如权利要求18所述的用途,其中所述的剂量单位形式中含有0.5mg至500mg的白藜芦醇。
20.如权利要求18或19所述的用途,其中所述的剂量单位形式中含有10mg至1000mg的多不饱和脂肪酸。
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KR (2) | KR101254454B1 (zh) |
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EP1633208A1 (en) | 2006-03-15 |
WO2004105517A1 (en) | 2004-12-09 |
EP2218342A3 (en) | 2011-01-05 |
CN1794925A (zh) | 2006-06-28 |
JP5335192B2 (ja) | 2013-11-06 |
EP2218342B1 (en) | 2018-07-04 |
JP2011184450A (ja) | 2011-09-22 |
US20060287256A1 (en) | 2006-12-21 |
DK2218342T3 (en) | 2018-10-22 |
JP5566946B2 (ja) | 2014-08-06 |
PL2218342T3 (pl) | 2019-01-31 |
KR101143719B1 (ko) | 2012-05-09 |
ES2687657T3 (es) | 2018-10-26 |
KR20120034228A (ko) | 2012-04-10 |
CN102125538B (zh) | 2014-05-07 |
EP2218342A2 (en) | 2010-08-18 |
KR101254454B1 (ko) | 2013-04-12 |
KR20060015737A (ko) | 2006-02-20 |
CN102125538A (zh) | 2011-07-20 |
US7582674B2 (en) | 2009-09-01 |
CN103211806A (zh) | 2013-07-24 |
JP2011184449A (ja) | 2011-09-22 |
JP2006528950A (ja) | 2006-12-28 |
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