CN105555289B - 可可多酚及其在治疗或预防嗜酸性食管炎中的效用 - Google Patents
可可多酚及其在治疗或预防嗜酸性食管炎中的效用 Download PDFInfo
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- CN105555289B CN105555289B CN201480050995.0A CN201480050995A CN105555289B CN 105555289 B CN105555289 B CN 105555289B CN 201480050995 A CN201480050995 A CN 201480050995A CN 105555289 B CN105555289 B CN 105555289B
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- procyanidin
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- eosinophilic esophagitis
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Abstract
本发明涉及可可多酚,特别是原花青素在治疗或预防嗜酸性食管炎中的效用。
Description
技术领域
本发明涉及用于治疗或预防嗜酸性食管炎(eosinophilic esophagitis)的可可多酚的效用。
背景技术
嗜酸性食管炎是一种由抗原引发或不由抗原引发的食管炎症状态。症状包括功能性腹痛、呕吐、发育迟缓、吞咽困难、食物嵌塞以及胃灼热(heartburn)。该疾病最初见于儿童,但也发生于成人中。正常的食道粘膜中通常不存在嗜酸性粒细胞。但是,在嗜酸性食管炎中,嗜酸性粒细胞渗入食道上皮,而且通常成簇地存在于上皮表面的附近。嗜酸性粒细胞的渗入常常与基底层的增厚相关联,基底层的增厚是对上皮炎症活动的反应。
目前有不同的策略可用于治疗嗜酸性食管炎,包括药物治疗、机械扩张和饮食调整。
在药物治疗中,发现皮质类固醇和质子泵抑制剂可减轻症状。还观察到,施用抗组胺药可减轻过敏反应。如果上皮肿胀威胁到发生食道阻塞,在这种严重的情况下,可考虑对食道进行机械扩张。
以前的营养治疗方案主要针对饮食调整,方法是从饮食中排除潜在的食物过敏原。因此,进行过敏评估,从而确定可能引起该病的那些过敏原。随后对饮食进行调整,排除所确定的过敏原。其他方法旨在提供不含任何潜在的过敏原的完全营养。例如,US 2008/0031814描述了不含致敏成分、因而预防过敏炎症状态进展的营养组合物。因此,现有技术的饮食旨在避免饮食中的致敏成分,而不是选择某些营养成分来治疗疾病。
所以,需要一种包含天然化合物的组合物,该组合物不仅不含主要的过敏原,而且能够有效预防或治疗嗜酸性食管炎。
发明内容
本发明的目的是为预防或治疗嗜酸性食管炎的问题提供新的和替代解决方案。已惊奇地发现,可可多酚可用于预防或治疗嗜酸性食管炎。利用建立的针对嗜酸性食管炎的小鼠模型评估了可用于治疗或预防嗜酸性食管炎的成分(Akei et al.,“Epicutaneousantigen exposure primes for experimental eosinophilic esophagitis in mice”,Gastroenterology,2005Sep;129(3):985-94(Akei等人,“表皮抗原暴露用于小鼠实验性嗜酸性食管炎”,《肠胃病学》,2005年9月,第129卷,第3期,第985-994页))。该模型利用多个参数,包括食道中嗜酸性粒细胞的数量,作为对嗜酸性食管炎的影响的指标。因此,该模型非常适用于测试用于治疗或预防嗜酸性食管炎的候选化合物。
因此,本发明涉及用于预防或治疗嗜酸性食管炎的组合物,该组合物包含至少一种原花青素。
该至少一种原花青素选自原花青素B1,原花青素B2,非为原花青素B1或B2的原花青素,原花青素B1、原花青素B2或所述非为原花青素B1或B2的原花青素的一种或多种多聚体,所述多聚体为二聚体至十聚体中的任一者;或所述原花青素的组合。
该组合物可包含按重量计0.01%至0.5%、或0.02%至0.1%、或0.04%至0.07%的原花青素B1或所述原花青素的多聚体。
该组合物可包含按重量计0.01%至1.0%、或0.1%至0.9%、或0.2%至0.3%的原花青素B2或所述原花青素的多聚体。
该组合物可包含按重量计0.5%至10%、或1%至5%、或1.5%至2%的非为原花青素B1或B2的原花青素或所述原花青素的多聚体。
该至少一种原花青素可包含在植物提取物或浓缩物内。
该植物提取物可以是葡萄或可可提取物。
该组合物可口服施用,可选地通过胃管喂食或局部口服。该组合物可施用于人类或宠物,特别是猫或狗。所述人类可以是年龄介于1个月和6岁之间的幼儿、年龄介于6至18岁之间的大龄儿童、或成年人。因此,该营养组合物可选自婴儿喂养组合物、较大婴儿配方产品、成长乳、婴儿谷物、或婴儿营养组合物。该组合物也可以是营养组合物、宠物营养组合物、口服营养补充剂、或药物产品。特别地,该营养组合物可选自饮料产品、酸乳产品、发酵乳、果汁、或谷物棒。该营养组合物可以是用于特定医疗目的的食物,诸如用于经口喂食的保健营养组合物、用于肠道喂食的营养产品、或胃肠外喂食产品。
附图说明
图1实验方案
图2食道中嗜酸性粒细胞的数量。收集食道并进行了组织学鉴定。对苏木精和伊红(H&E)染色的玻片上每个高倍视野(hpf)中的嗜酸性粒细胞进行了识别和计数。示出了在整个食道的一个高倍视野中发现的嗜酸性粒细胞的最大数量。表示了存在于食道上皮中的嗜酸性粒细胞的最大数量。使用了以下化合物:6%可可提取物、3%苹果提取物、1%表儿茶素,其中百分比表示多酚的量。
定义
“嗜酸性食管炎”是食道的一种炎症状态。症状包括功能性腹痛、呕吐、发育迟缓、吞咽困难、食物嵌塞以及胃灼热。其特征为食道上皮中存在嗜酸性粒细胞渗入。嗜酸性粒细胞的渗入可与基底层的增厚相关联。根据ICD-9(国际疾病分类第9版)将其指定为530.13。如果在食道的粘膜活检中发现每个“高倍视野”(在下文定义)中存在15个以上的嗜酸性粒细胞,那么就可考虑诊断为嗜酸性食管炎。
“植物酚”是一类天然有机化合物。其包含一个或多个酚基。这里只考虑存在于植物中的酚以及与天然存在于植物中的酚相同的人工合成酚。
“酚基”是包含键合到羟基的苯基的基团。酚基的碳环上的氢可用另外的残基(例如,羟基-、烷基-、烯烃-残基、形成羧基的环C等)取代。特别优选的取代基是另外的羟基。
本发明中的“植物多酚”是包含2个以上酚基的酚。
“原花青素”是多酚的一种形式。多酚由一个以上的芳香环构成,其中每个芳香环包含至少一个羟基。黄酮类是多酚的一个亚类,其具有C6-C3-C6的主链结构。原花青素是黄酮类的其中一族,由黄烷-3-醇单体和其相应的低聚物构成,其中单体和低聚物常常通过4→6或4→8连接键结合。所述原花青素的多聚体形式也是天然存在的。对于本发明中的原花青素的定义,参考Hammerstone,John F.;Lazarus,Sheryl A.;Schmitz,Harold H.(August2000,“Procyanidin content and variation in some commonly consumed foods”。TheJournal of nutrition 130(8S Suppl):2086S–92S.PMID 10917927)(Hammerstone JohnF、Lazarus Sheryl A、Schmitz Harold H,2000年8月,“一些通常摄入食物中的原花青素含量和变化”,《营养学杂志》,第130卷8S增刊:第2086S–92S页。PMID 10917927),特别参考前言部分。
本发明使用的“高倍视野(HPF)”指在所用显微镜的物镜的最大放大率下的可见区域。这可表示400×放大级别。
本发明使用的“局部口服”是一种施用形式,其中组合物局部施加到食道粘膜,以便食道粘膜直接吸收该组合物。这种施用形式旨在避免食道之后的消化道吸收该组合物。局部口服施用的典型形式是以喷雾形式施用,即经由口腔喷布,然后吞咽到食道中。
具体实施方式
各部分标题起到阐明主题的作用,不应理解为限制该主题。如果公开了值的范围,那么认为该范围涵盖每一单个值,特别是每个整数。除非另有说明,用%表示的值是指重量/重量(w/w)值。已惊奇地发现,某些可可多酚可用于减少嗜酸性粒细胞的数量。这个发现是从针对嗜酸性食管炎的小鼠模型得到的。因此,可以推论,植物酚可用于治疗或预防嗜酸性食管炎,这种疾病的特征为某些组织中嗜酸性粒细胞的数量增加。
组合物
本发明的组合物可包含若干成分,特别是多酚。优选的成分是至少一种原花青素。原花青素可包含在可可提取物或浓缩物内。具体地,本发明的组合物可包含可可提取物或浓缩物,继而包含至少含有原花青素的多酚。在具体实施例中,该组合物包含含有至少一种原花青素的多酚,以及其他多酚。在另一个优选实施例中,多酚以一定浓度存在于提取物或浓缩物中,或/和以可发现的比例存在于可可提取物或浓缩物中。
植物多酚
该组合物包含至少一种植物多酚。植物多酚包含至少2、3、4、5或6个酚残基。特别优选的是包含2个酚残基的植物酚。植物酚优选地仅由氢、碳和氧构成。植物酚优选地包含选自以下的残基,或由选自以下的残基构成:至少一个环己烷残基、酚残基、H-残基、OH-残基、C-残基、CO2H-残基、乙烷残基和-O-残基的残基,或由选自至少一个环己烷残基、酚残基、H-残基、OH-残基、C-残基、CO2H-残基、乙烷残基、-O-残基。
该组合物可包含至少一种、至少两种、至少三种或至少四种不同的植物多酚。可以预期,植物多酚的组合将对嗜酸性食管炎表现出协同功效。该酚是存在于天然植物来源中的酚。天然来源可以是可可或葡萄。可通过任何已知的提取技术(例如,用水、或乙醇和乙醚之类的有机溶剂来提取)从这些天然来源中提取酚。
该组合物包含“原花青素”。具体地讲,该组合物可包含原花青素B1(顺式,反式"-4,8"-二-(3,3',4',5,7-五羟基黄烷))、原花青素B2(4,8"-二-[(+)-表儿茶素]、顺式,顺式"-4,8"-二(3,3',4',5,7-五羟基黄烷))、非为原花青素B1或B2的其他原花青素。特别地,该组合物可包含所述原花青素的多聚体。特别优选的是二至二十聚体、五至十五聚体、或七至十聚体。
该组合物可包含至少一种原花青素B1或/和它们的一种或多种多聚体。
该组合物可包含至少一种原花青素B2或/和它们的一种或多种多聚体。
该组合物可包含至少一种非为原花青素B1或B2的原花青素或/和它们的一种或多种多聚体。
该组合物可包含至少一种原花青素B1和至少原花青素B2、或/和原花青素B1和原花青素B2的一种或多种多聚体。
该组合物可包含至少一种原花青素B1或/和它们的一种或多种多聚体;以及至少一种非为原花青素B1或B2的原花青素或/和它们的一种或多种多聚体。
该组合物可包含至少一种原花青素B2或/和它们的一种或多种多聚体;以及至少一种非为原花青素B1或B2的原花青素或/和它们的一种或多种多聚体。
该组合物可包含至少一种原花青素B1或/和它们的一种或多种多聚体;以及至少一种原花青素B2或/和它们的一种或多种多聚体;以及至少一种非为原花青素B1或B2的原花青素或/和它们的一种或多种多聚体。
还设想该组合物包含另外的非原花青素的多酚。
在具体实施例中,该组合物不包含表儿茶素。还设想了这些植物酚的混合物。具体地讲,该混合物可包含至少1、2、3、4、5、6、7、8、9、10、11、12种上述多酚。该组合物可在其中包含上述酚的任何排列。
在优选实施例中,包含多酚(该多酚包括原花青素)的用于治疗或预防嗜酸性食管炎的组合物从可可中获得,因此从可可多酚提取物中获得。
提取物或浓缩物中多酚的总量可以是按重量计介于20%和60%之间、介于30%和55%之间、或介于40%和50%之间。
该提取物或浓缩物可包含按重量计0.01%至5%、或0.1%至0.5%、或0.5%至0.15%的原花青素B1或所述原花青素的多聚体。
在优选实施例中,该提取物或浓缩物包含按重量计1%至.0%、或2%至7%、或3%至5%的原花青素B2或所述原花青素的多聚体。
在优选实施例中,该提取物或浓缩物包含按重量计0.5%至10%、或1%至5%、或1.5%至2%的非为原花青素B1或B2的其他原花青素或所述原花青素的多聚体。
可将该提取物或浓缩物稀释以用于预防或治疗嗜酸性食管炎的组合物中。
在一些实施例中,该组合物可包含基于该组合物重量计约1%至20%、2%至15%、3%至10%、或5%至7%的提取物或浓缩物。
在优选实施例中,用于预防或治疗嗜酸性食管炎的组合物包含按重量计0.01%至0.5%、或0.02%至0.1%、或0.04%至0.07%的原花青素B1或所述原花青素的多聚体。
在优选实施例中,该组合物包含按重量计0.01%至1.0%、或0.1%至0.9%、或0.2%至0.3%的原花青素B2或所述原花青素的多聚体。
在优选实施例中,该组合物包含按重量计0.5%至10%、或1%至5%、或1.5%至2%的非为原花青素B1或B2的其他原花青素或所述原花青素的多聚体。
特别优选的是原花青素B1、原花青素B2、或非为原花青素B1或B2的其他原花青素的二至二十聚体、五至十五聚体、或七至十聚体。
制剂
上述组合物可配制为液体或固体形式。液体形式可配制为适用于喷雾的形式,即喷雾形式。这可通过将装有该组合物的隔室连接到喷嘴来实现。液体经过喷嘴输送时被雾化,使获得的液滴均匀分布到表面上。经过喷嘴输送液体的各种方法是技术人员已知的。例如,装有该组合物的容器可相比周围大气压力而言受压。或者,可利用泵装置来经过喷嘴输送喷雾。使用喷雾可(例如)经由口腔将该组合物喷入食道,从而使该组合物直接与食道粘膜接触。随后该组合物可由粘膜吸收,然后在体内实现系统性分布。
该组合物还可包含至少一种其他的活性剂、载体、媒介物、赋形剂或助剂,这些试剂可由本领域的技术人员在阅读本公开之后确定。
该组合物可以呈口服营养补充剂、营养组合物或药物产品的形式。营养组合物、口服营养补充剂或药物产品可包含本发明的组合物或试剂盒。
营养组合物
如本文所用,术语“营养组合物”包括但不限于完全营养组合物、部分或不完全营养组合物、以及特定于疾病和病况的营养组合物。完全营养组合物(即包含所有必需的大量和微量营养素的组合物)可用作患者唯一的营养来源。患者可从这种完全营养组合物接收到100%的营养需求。部分或不完全营养组合物不包含所有必需的大量和微量营养素,并且不可用作患者唯一的营养来源。部分或不完全营养组合物可用作营养补充剂。口服补充营养组合物主要或仅仅包含所要求保护的组合物的必要活性成分(植物酚),并且可在患者的常规营养之外被摄入。
特定于疾病或病况的营养组合物是提供营养素或药物的组合物,并且可以是完全营养组合物或部分营养组合物。
营养组合物可另外包含以下营养素和微量营养素:蛋白质来源、脂质来源、碳水化合物来源、维生素和矿物质。该组合物还可包含抗氧化剂、稳定剂(以固体形式提供时)或乳化剂(以液体形式提供时)。在优选实施例中,该组合物是基于氨基酸的配方,也就是说氨基酸的唯一来源是游离氨基酸。
因此,在另一个实施例中,该营养组合物还包含一种或多种氨基酸。氨基酸的非限制性例子包括丙氨酸、精氨酸、天冬酰胺、天门冬氨酸、瓜氨酸、半胱氨酸、谷氨酸、谷氨酰胺、甘氨酸、组氨酸、羟脯氨酸、羟丝氨酸、羟酪氨酸、羟赖氨酸、异亮氨酸、亮氨酸、赖氨酸、蛋氨酸、苯丙氨酸、脯氨酸、丝氨酸、牛磺酸、苏氨酸、色氨酸、酪氨酸、缬氨酸、HICA(α-羟基异己酸)、HIVA(α-羟基异戊酸)、HIMVA(α-羟基甲基戊酸),或它们的组合。在优选实施例中,氨基酸的非限制性例子包括脯氨酸、羟脯氨酸、羟酪氨酸、羟赖氨酸、羟丝氨酸,以及它们的组合。
在又一个实施例中,该营养组合物可包含矿物质,诸如钠、钾、钙、磷、镁、氯、铁、锌、铜、锰、氟、铬、钼、硒、碘,或它们的任何组合。
在又一个实施例中,该营养组合物还包含维生素,诸如维生素A、维生素E、维生素C、维生素B1、维生素B2、泛酸、维生素B6、维生素B12、烟酸、叶酸、生物素、胆碱,或它们的任何组合。
在一个实施例中,该营养组合物选自婴儿喂养组合物、较大婴儿配方产品、成长乳、婴儿谷物或婴儿营养组合物。这些产品特别适用于处理和解决预防或减轻婴儿和幼儿的嗜酸性食管炎症状的问题。但是,也可选择如下所述的饮料和粉末(小袋形式)之类的其他产品用于大龄儿童和成年人。
在另一个实施例中,该营养组合物选自饮料产品、基于氨基酸的饮料、酸乳产品、发酵乳、果汁、小袋形式的干粉、或谷物棒。这些营养组合物非常适用于向大龄儿童和成年人施用植物酚。该营养组合物可富含植物酚,并且具有可信形象以向消费者提供健康导向的功能营养组合物。
临床环境,诸如医院、诊所或有老年人的家庭中,可能特别需要能够减轻嗜酸性食管炎症状的产品。因此,在另一个实施例中,该营养组合物是用于特定医疗目的的食物,诸如用于经口喂食的保健营养组合物和/或用于肠道或胃肠外给养的营养产品。在后一种情况下,该营养组合物将仅包含适用于胃肠外给养的成分。适用于胃肠外给养的成分是本领域的技术人员已知的。具体地讲,胃肠外给养组合物将包含纯的或基本纯的形式的植物酚(即通常不是以只富含植物酚的植物提取物的形式提供),但该组合物也可包含已知适用于胃肠外营养的其他成分。本发明的另一个优点是,植物酚可以相对高的局部浓度和相对低的量的药物营养组合物提供,因此可对有这种需求的患者有效施用。
试剂盒
以上组合物也可作为试剂盒提供。在这些试剂盒中,上述组合物的所有或部分成分以单独(即不混合的)的形式提供。本发明的试剂盒一方面可包含植物酚,另一方面可包含单独形式的所有其余成分。本发明的试剂盒可包含至少两种或三种以单独形式提供的植物酚。在可供选择的实施例中,该试剂盒可包含上述组合物的单独形式的每种成分。
治疗效用和方法
本发明的组合物或试剂盒可用于治疗或预防嗜酸性食管炎,或具体地讲用于减少上皮(特别是食道上皮)嗜酸性粒细胞的数量。本发明的组合物或试剂盒也可用于治疗或预防嗜酸性食管炎的方法中,或具体地讲用于减少上皮(特别是食道上皮)嗜酸性粒细胞的数量的方法中。
嗜酸性粒细胞数量减少被定义为,在食道粘膜活检中,发现在显微镜高倍视野中的嗜酸性粒细胞减少,在患有嗜酸性食管炎的人中,其数量减少到低于10至20,具体地低于15。因此,本发明中的减少是指与动物模型中的阳性对照比较时的显著减少。本发明中的减少可以是指,在人食道的粘膜活检中,显微镜高倍视野中的数量减少至低于19、18、17、16、15、14、13、12、11、10、9、8、7、6、5、4、3、2、1,或减少至0。或者,可参照患有嗜酸性食管炎的受试对象所具有的或如果不使用本发明的组合物来采取预防措施而预期具有的嗜酸性粒细胞的数量,来定义这种减少。因此,减少可以是指,参考在患有嗜酸性食管炎的动物或人类食道粘膜活检中于显微镜高倍视野中发现的嗜酸性粒细胞的数量,数量上的百分比减少(减少至少50%、60%、70%、80%、90%、95%、99%,或减少100%)。或者,本发明中的减少可以是指,参考在患有嗜酸性食管炎的人类食道粘膜活检中于显微镜高倍视野中发现的嗜酸性粒细胞的数量,在数量上绝对减少5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20或20个以上。参考值可在10至20的范围内,或可以是15。可在治疗后5、10、15、20、25、30、60、120天后观察减少。
该组合物和试剂盒可以适用于口服或局部施用的形式提供,然后可相应地施用。可在受试对象发生嗜酸性食管炎症状之前开始施用,也可在该症状出现的同时或该症状显现之后开始施用。施用可进行1、20、30、60、120、360天或更长时间。如果受试对象是人,那么被施用该组合物的受试者可以是年龄介于4个月和6岁之间、年龄介于6个月和18岁之间、或成年人。
在一个实施例中,该组合物旨在由动物(优选为猫或狗)摄入。与人类似的是,可在动物(特别是驯养动物和宠物动物)中观察到嗜酸性食管炎。有利的是,本发明提供可由伴侣动物的主人提供给伴侣动物的液体。
施用于人的该组合物中的总植物酚的量优选地在3mg/kg体重/天到100mg/kg体重/天的范围内,优选地为10至50mg/kg体重/天。优选地,该组合物的用量为从约25mg至10g/天、从50mg至10g/天,优选地从100mg至5g/天,甚至更优选地从300mg至1g/天。这些优选剂量一方面可每天为相关患者提供足够的植物酚以提供期望的健康益处,另一方面可避免植物酚过量,以防范对患者的任何潜在不良或毒性作用风险。
制备方法
提供了用于制备上述组合物的方法,该方法包括提供至少一种上述植物酚;可选地添加至少一种另外的成分(例如,选自一种或多种氨基酸、脂肪或碳水化合物);可选地添加至少一种营养素或微量营养素;添加载体或/和水。
本领域的技术人员将理解,他们可以自由地组合本文所公开的本发明的所有特征。具体地讲,可将针对本发明不同实施例所描述的特征进行组合。根据附图和实例,本发明的其他优点和特征将显而易见。
实例
实例1:多酚对嗜酸性粒细胞数的影响
对5至8周大的雌性Balb/c小鼠表皮施用200μg致敏提取物,使其过敏。剃掉小鼠背部上小部分的毛。用生物密封(bio-occlusive)透明敷料2461(强生公司(Johnson andJohnson))和创可贴将含有过敏原的消毒纱布贴片(1×1cm)固定到小鼠皮肤上。贴片在皮肤上连续保留4至7天的致敏期,直到被感觉到或在第8天将贴片移除。致敏期最后一天过后数天(第21至28天),第30天时,麻醉小鼠并将其暴露于滴鼻激发(intranasal challenge)(100μg)实验中,32天时收集小鼠。
烟曲霉菌抗原提取物和房屋尘螨提取物是从北卡罗来纳州勒努瓦格里尔实验室(Greer Laboratories,Lenoir,NC)获得,用生理盐水将其稀释至100μg/μL。
使用食物中的植物酚提取物测试了植物酚的效果,这些食物来源于包含6%(w/w)可可提取物的可可提取物(45%多酚的可可提取物的水稀释物,西班牙Monteloeder公司)、包含多酚的3%(w/w)苹果提取物(西班牙Monteloeder公司;多酚含有80%根皮苷和根皮素;并含有表儿茶素)以及得自西班牙Monteloeder公司的1%(w/w)表儿茶素。通过使用所述稀释物,最终饮食中的表儿茶素含量为0.5%至1%(w/w)。因此,可排除表儿茶素是影响任何所观察到的差异的相关因素。
小鼠数量 | 表皮致敏 | 激发 | 治疗 | |
A组 | 8 | 3X生理盐水 | 1X ASP | 无 |
B组 | 8 | 3X ASP | 1X ASP | 无 |
C组 | 8 | 3X ASP | 1X ASP | 可可提取物 |
D组 | 8 | 3X ASP | 1X ASP | 苹果提取物 |
E组 | 8 | 3X ASP | 1X ASP | 表儿茶素 |
收集食道并用苏木精-伊红染色,统计嗜酸性粒细胞的数量(最大数/高倍视野,见图2)。
与阳性对照相比,观察到食道中嗜酸性粒细胞明显减少,并且在食道和食道上皮中存在可可多酚。这提示得自可可的酚在减少过敏原所致的嗜酸性负载中有更广泛的作用。观察到表儿茶素没有效果,这意味着所用可可提取物的其他主要成分(即,1.0%原花青素B1、4.0%原花青素B2、30%其他原花青素的一至十聚体)导致了了所观察到的效果。
实例2:临床试验
将基于氨基酸的组合物PEDIATRIC(还包含下表所示的提取物)施用于7组患有嗜酸性食管炎的人,其中每组20至30人,年龄介于18至60之间,这些患者在食道、胃、十二指肠镜检查所获得的粘膜的活检中,每个高倍视野中均显示存在15个以上的嗜酸性粒细胞。
PEDIATRIC在标准稀释下是0.8kcal/ml的配方,该配方具有以kcal百分比计的以下成分:12%蛋白质(游离氨基酸)、63%碳水化合物和25%脂肪。MCT:LCT之比为70:30;n6:n3之比为7.7:1;渗透压浓度为360mOsm/kg水;89%游离水;其完全满足或超过DRI中关于蛋白质和25种关键维生素和矿物质的要求;3.0g/L补充谷氨酰胺;2.0g/L补充左旋精氨酸。
该可可提取物包含6%多酚(从含有45%多酚的可可提取物(得自西班牙Monteloeder公司)制备得到)。得自Monteloeder公司的该可可提取物包含1.0%儿茶素、9.0%表儿茶素、1.0%原花青素B1、4.0%原花青素B2、30%其他原花青素的一至十聚体;苹果提取物包含3%(w/w)的多酚(西班牙Monteloader公司;多酚含有80%根皮苷和根皮素);1%表儿茶素,得自西班牙Monteloader公司。
受试对象数量 | 试剂 | |
A组 | 15 | 水 |
B组 | 15 | 6%可可提取物 |
C组 | 15 | 3%苹果提取物 |
D组 | 15 | 1%表儿茶素 |
分别以500mg多酚的日剂量将提取物施用于受试对象。嗜酸性粒细胞的数量确定为,研究开始后第15天和第30天时,在食道、胃、十二指肠镜检查所获得的粘膜的活检中,每个高倍视野中的可见嗜酸性粒细胞数。研究中还观察了已知的相关症状,如吞咽困难、食物嵌塞和胃灼热。
Claims (21)
1.组合物在制备用于预防或治疗嗜酸性食管炎的产品中的用途,所述组合物包含可可多酚提取物,所述可可多酚提取物包含原花青素B1;原花青素B2;和至少一种非为原花青素B1或B2的原花青素多聚体;所述多聚体为二聚体至十聚体中的任一者。
2.根据权利要求1所述的用途,其中所述组合物包含0.01%至0.5%、或0.02%至0.1%、或0.04%至0.07%(w/w)的原花青素B1。
3.根据权利要求1所述的用途,其中所述组合物包含0.01%至1.0%、或0.1%至0.9%、或0.2%至0.3%(w/w)的原花青素B2。
4.根据权利要求2所述的用途,其中所述组合物包含0.01%至1.0%、或0.1%至0.9%、或0.2%至0.3%(w/w)的原花青素B2。
5.根据权利要求1所述的用途,其中所述组合物包含0.5%至10%、或1%至5%、或1.5%至2%(w/w)的非为原花青素B1或B2的原花青素多聚体。
6.根据权利要求2所述的用途,其中所述组合物包含0.5%至10%、或1%至5%、或1.5%至2%(w/w)的非为原花青素B1或B2的原花青素多聚体。
7.根据权利要求3所述的用途,其中所述组合物包含0.5%至10%、或1%至5%、或1.5%至2%(w/w)的非为原花青素B1或B2的原花青素多聚体。
8.根据权利要求4所述的用途,其中所述组合物包含0.5%至10%、或1%至5%、或1.5%至2%(w/w)的非为原花青素B1或B2的原花青素多聚体。
9.根据权利要求1所述的用途,其中所述组合物口服施用。
10.根据权利要求1所述的用途,其中所述组合物局部口服施用。
11.根据权利要求1所述的用途,其中所述组合物以喷雾形式施用。
12.根据权利要求1所述的用途,其中所述组合物施用于人类或宠物。
13.根据权利要求12所述的用途,其中所述人类是年龄介于1个月和6岁之间的幼儿、年龄介于6至18岁之间的大龄儿童、或成年人。
14.根据权利要求1所述的用途,其中所述组合物施用于猫或狗。
15.根据权利要求1-14中任一项所述的用途,其中所述组合物是营养组合物、口服营养补充剂或药物产品。
16.根据权利要求15所述的用途,其中所述营养组合物选自婴儿喂养组合物、基于氨基酸的饮料或配方产品、较大婴儿配方产品、成长乳。
17.根据权利要求15所述的用途,其中所述营养组合物选自婴儿谷物、婴儿营养组合物。
18.根据权利要求15所述的用途,其中所述营养组合物选自饮料产品、小袋形式的干粉、谷物棒。
19.根据权利要求15所述的用途,其中所述营养组合物选自酸乳产品、发酵乳、果汁。
20.根据权利要求15所述的用途,其中所述营养组合物是用于特定医疗目的的食物。
21.根据权利要求15所述的用途,其中所述营养组合物是用于经口喂食的保健营养组合物、用于肠道给养的营养产品、或胃肠外给养产品。
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原花青素抑制哮喘小鼠气道炎症及气道高反应性;周丹阳等;《南京医科大学学报(自然科学版)》;20110727(第7期);摘要,982页左栏第2段,第2.3节,图3,第3节讨论 * |
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US10350252B2 (en) | 2019-07-16 |
JP2016531931A (ja) | 2016-10-13 |
BR112016005727B1 (pt) | 2021-09-08 |
EP3049094B1 (en) | 2020-06-10 |
EP3049094A1 (en) | 2016-08-03 |
CA2920942C (en) | 2022-05-03 |
AU2014322996B2 (en) | 2019-12-12 |
CN105555289A (zh) | 2016-05-04 |
US20160213721A1 (en) | 2016-07-28 |
WO2015040223A1 (en) | 2015-03-26 |
ES2803549T3 (es) | 2021-01-27 |
BR112016005727A2 (zh) | 2017-08-01 |
JP6625986B2 (ja) | 2019-12-25 |
CA2920942A1 (en) | 2015-03-26 |
AU2014322996A1 (en) | 2016-02-04 |
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