CN112638474A - 代谢障碍的植物调节剂 - Google Patents
代谢障碍的植物调节剂 Download PDFInfo
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- CN112638474A CN112638474A CN201980056647.7A CN201980056647A CN112638474A CN 112638474 A CN112638474 A CN 112638474A CN 201980056647 A CN201980056647 A CN 201980056647A CN 112638474 A CN112638474 A CN 112638474A
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- cashew nut
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Abstract
公开了也起到PPAR‑γ激动剂作用的MMP‑9的基于植物的抑制剂,以及此类基于植物的抑制剂/激动剂在调节代谢障碍中的用途。所述基于植物的抑制剂/激动剂至少是从腰果属(Anacardium)获得的提取物。
Description
与相关申请的交叉引用
本申请要求2018年8月31日提交的美国专利申请号62/725,448的利益,所述申请的公开内容整体通过引用并入本文。
技术领域
本发明总的来说涉及MMP-9抑制剂和PPAR-γ激动剂,并且更具体来说涉及也起到PPAR-γ激动剂作用的MMP-9的基于植物的抑制剂,以及此类基于植物的抑制剂/激动剂在调节一种或多种代谢障碍中的用途。
背景技术
在正常情况下,细胞外基质(“ECM”)的合成和降解受到严格调控。尽管ECM的有计划降解是组织修复和重塑的重要特点,但ECM的不受控制的变化与许多疾病例如炎症、癌症和心血管功能障碍相关。在心血管疾病中,心肌梗塞(“MI”)在美国是最高发的心脏病症之一。作为心肌梗塞后重塑发展为充血性心力衰竭的结果,它与长期并发症和高死亡率相关。基质金属蛋白酶(“MMP”)是在心脏ECM重塑中发挥关键作用的关键酶。MMP是一类结构相关的锌依赖性内肽酶,其降解ECM的几种成分,它们的表达和/或活性的提高与各种不同的病理生理过程相关。具体来说,MMP-9(也被称为明胶酶B)在心肌ECM重塑中发挥主要作用。一直以来,已发现MMP-9在MI后的早期增加,并且其水平与心力衰竭的严重程度呈正相关。因此,降低MMP-9的表达水平和/或活性可能在心血管健康中具有有益作用。
MMP-9也是参与关节软骨基质降解的酶之一。软骨是关节结构的主要组分,并由包埋在密集且高度组织的ECM中的软骨细胞组成。ECM由软骨细胞合成,并由主要包含II型胶原蛋白的胶原网络以及糖胺聚糖(“GAG”)和相关蛋白聚糖组成。胶原蛋白形成纤维状网络,并为软骨基质提供抗张强度,而聚集蛋白多糖则是主要的软骨蛋白聚糖,将水吸入到基质中并使其抗压。随着聚集蛋白多糖分解,胶原蛋白的降解是关节炎的中心特征。已知促炎性细胞因子例如肿瘤坏死因子α(“TNF-α”)、白介素1(“IL-1”)和IL-6在关节软骨中的软骨基质降解中,通过导致刺激聚集蛋白多糖酶和基质金属蛋白酶(如MMP-9)的产生的事件级联而发挥重要作用。植物提取物引起的MMP-9减少表明所述提取物通过维持完整软骨而有助于更健康的关节结构的能力。
MMP-9似乎参与许多病理状况的酶过程。癌症(乳腺癌、胰腺癌、肺癌、膀胱癌、结肠直肠癌、卵巢癌、前列腺癌和脑癌)、牙周疾病(牙周炎和牙龈炎)、糖尿病的继发并发症(动脉粥样硬化中的斑块形成)、伤口愈合延迟(下肢静脉溃疡)、炎症性肠病并发症(克罗恩病)、神经炎症(多发性硬化症)和胃溃疡是受此酶存在影响的众多人类疾病中的几个。因此,调节MMP-9的表达和/或活性对于矫正许多慢性和急性疾病来说至关重要。
胰岛素抗性和葡萄糖耐受受损是代谢综合征中的两个关键失衡,与腹型肥胖、高血压和血脂异常密切相关。受这些障碍影响的人发生心血管疾病、II型糖尿病、慢性低度局部组织炎症的风险更大,并且对其他疾病状况例如脂肪肝、睡眠紊乱和癌症的易感性提高。多年来,已开发了几种抗高血糖产品,通过靶向方式增加胰岛素分泌、使组织和器官对胰岛素敏感、提高葡萄糖的摄取和运输以及减少肠道中碳水化合物的吸收来应对这些挑战。在这些靶中,例如过氧化物酶体增殖物激活受体γ(“PPAR-γ”)通过控制由脂肪组织分泌的许多因子例如脂联蛋白、瘦蛋白、抵抗素和肿瘤坏死因子-α(TNF-α)的表达来影响外周组织的胰岛素敏感性。PPAR-γ还可以直接上调4型葡萄糖转运蛋白(Glut4),并因此调节葡萄糖体内平衡。
PPAR是调控靶基因表达的配体激活的转录因子。在内源性或外源性激动剂结合后,PPAR受体与类视黄醇X受体(RXR)异二聚化,并与位于靶基因启动子区中的PPAR响应元件(PPRE)结合,引起基因表达的调控。除了在维持代谢稳态方面的作用之外,PPAR还调控参与脂质代谢、脂肪形成和炎症的基因的表达。
存在至少3种具有多样性组织表达的PPAR亚型(α、β和γ),这表明每种这些亚型可能具有特定功能。其中,已知PPAR-γ具有两种同工型PPAR-γ1和PPAR-γ2。PPAR-γ1在脂肪组织、大肠和造血细胞中丰富表达,并在肾脏、肝脏、肌肉、胰腺和小肠中以较低程度表达。相反,PPAR-γ2限于白色和棕色脂肪组织。
PPAR-γ的活化是前脂肪细胞前体细胞分化成对葡萄糖代谢的调节具有最终作用的脂肪细胞的过程中的关键步骤之一。例如,已知PPAR-γ的强力外源激动剂噻唑烷二酮(又称“TZD”或格列酮类,例如曲格列酮、罗格列酮和吡格列酮)通过这种途径改善胰岛素响应性,增加脂肪细胞的葡萄糖摄取和脂质储存,使其成为糖尿病的良好干预选择。
植物药在大多数这些疾病的管理中发挥重要作用,并且植物是代谢障碍的天然调节剂的潜在来源。因此,对含有调节剂的植物和作为潜在治疗剂的促进健康的植物成分的研究兴趣日益增长。药用植物为在长期暴露后可能有毒的化学调节剂提供了一种安全、成本效益高的生态替代品。
腰果树(Anacardium occidentale Linn)最初来自于亚马逊地区,后来被移植到印度、东非和其他国家进行种植。这种树产生采取膨胀果梗形式的非常奇特的果或果实。在这种果梗末端的外部,腰果坚果生长在其自身的灰色肾形硬壳中。这种壳具有柔软的革质外皮和围绕果仁的被称为果壳或种皮的薄且坚硬的内皮。在这两层皮之间是一个含有腰果壳液的蜂窝状结构。这种液体包含腰果酸、腰果酚和腰果二酚以及其他成分。腰果酸是一种水杨酸,而腰果酚和腰果二酚是取代的酚。
已研究了所述果实的各个部分的用途。除了作为可食用食物之外,来自于腰果果实的汁被用于饮料中,而果实提取物在体重管理方面显示出益处。已提取了腰果壳液用于各种不同的工业和农业应用,包括摩擦衬片、涂料、层压树脂、橡胶混配树脂、腰果水泥、基于聚氨酯的聚合物、表面活性剂、环氧树脂、铸造化学品、化学中间体、杀虫剂和杀真菌剂。腰果种皮已被用于鞣料中。
作为健康生活方式和均衡健康饮食的一部分,补充被认为是调节各种不同代谢障碍的重要手段。正如上文提到的,对于具有此类调节活性的有效、无毒的天然化合物存在着需求。本发明提供了一种这样的解决方案。
发明内容
本文提供了一种包含儿茶素类的植物提取物,其中所述提取物已被标准化至以所述提取物的总重量计约15.0重量/重量%或更高的儿茶素含量,其中所述植物提取物表现出对一种或多种代谢障碍的调节性质,并且其中所述植物提取物至少包含从腰果属(Anacardium)获得的提取物。优选地,所述植物提取物至少是从腰果(Anacardiumoccidentale L.)获得的提取物。具体来说,所述植物提取物至少从腰果(Anacardiumoccidentale L.)果实的种皮获得。
在另一个实施方式中,本发明涉及一种包含腰果(Anacardium occidentale L.)种子的种皮的植物提取物的组合物,其中所述植物提取物表现出一种或多种代谢障碍的调节。优选地,所述植物提取物以约1.0μg/mL或更高的量,更优选地以约1.0μg/mL至约2000.0μg/mL的量,甚至更优选地以约50.0μg/mL至约500.0μg/mL的量存在于所述组合物中。一方面,所述组合物表现出MMP-9抑制。在这种情况下,所述植物提取物以约1.0μg/mL至约2000.0μg/mL的量存在。另一方面,所述组合物表现出PPAR-γ激动剂活性。在这种情况下,所述植物提取物以约50.0μg/mL至约2000.0μg/mL的量存在。
在另一个实施方式中,本发明提供了一种对一种或多种代谢障碍具有调节性质的膳食补充剂,其包含治疗有效量的腰果种皮提取物。优选地,所述腰果种皮提取物以约1.0μg/mL或更高的量存在于所述补充剂中。
本发明还提供了一种通过给药包含浓度为约1.0μg/mL至约2000.0μg/mL的腰果(Anacardium occidentale L.)种子的种皮的植物提取物的组合物在对象中调节一种或多种代谢障碍的方法。
附图说明
图1是腰果种皮提取物在0分钟(开始)至20分钟的保留时间内在275nm波长下的HPLC色谱图。
图2是腰果种皮提取物的LC/MS和LC/PDA(波长为280和350nm)色谱图。
图3是示出了使用各种不同浓度的腰果种皮提取物获得的基质金属蛋白酶9(MMP-9)的抑制百分率的图。
图4是示出了使用各种不同浓度的腰果种皮提取物获得的过氧化物酶体增殖物激活受体γ(PPAR-γ)的配体结合百分率的图。
发明详述
本发明是基于下述令人吃惊的发现,即腰果(Anacardium)的种皮含有明显高的某些类黄酮。具体来说,已发现腰果种皮的提取物包含儿茶素和表儿茶素作为主要组分以及原花青素类。本文中提到的数据证实了腰果种皮提取物可能在调节一种或多种代谢障碍中有用。
对于本申请来说,术语“组合物”是指治疗、改善、促进、提高、管理、控制、维持、优化、修改、减轻、抑制或阻止与天然状态、生物过程或疾病或障碍相关的特定状况的产品。例如,组合物在对象中改善肿瘤转移的抑制和/或减轻炎症等。术语组合物包括但不限于包含有效量的提取物、其至少一种组分或其混合物的药品(即药物)、非处方药(OTC)、化妆品、食品、食品成分或膳食补充剂组合物。示例性的组合物包括霜剂、化妆用洗剂、面膜或粉剂,或作为乳液、洗剂、搽剂泡沫、片剂、膏药、颗粒剂或软膏。组合物还可以包括饮料,例如加入有效量的提取物的饮料或含有有效量的提取物的茶包。含有有效量的提取物的食品组合物的非限制性实例包括烘焙食品、蛋白粉、肉制品、乳制品和糖食。
当在本文中使用时,术语“提取物”或“植物提取物”是指包含至少腰果属植物(例如Anacardium humile、Anacardium othonianum、Anacardium giganteum、Anacardiumnanum、Anacardium negrense和/或腰果(Anacardium occidentale))、优选为腰果(Anacardium occidentale L.)的物质的一种或多种活性成分的固体、半流体或液体物质或制剂。优选地,所述活性成分源自于腰果种皮的提取物。所述提取物可以使用溶剂例如水、1至4个碳原子的短链醇类(例如甲醇、乙醇、丁醇等)、乙烯、丙酮、己烷、醚、氯仿、乙酸乙酯、乙酸丁酯、二氯甲烷、N,N-二甲基甲酰胺(“DMF”)、二甲基亚砜(“DMSO”)、1,3-丁二醇、丙二醇及其组合来制备,但是也可以使用所述粗提取物在此类溶剂中的级分制备。可以使用任何提取方法,只要它确保所述活性成分的提取和保护即可。
当在本文中使用时,术语纯化合物、组合物、提取物、提取物混合物、提取物组分和/或活性药剂或成分或其组合的“有效量”或“治疗有效量”,是指在剂量和时间长度上足以有效实现所需结果的量。例如,所述“有效量”或“治疗有效量”是指本发明的纯化合物、组合物、提取物、植物提取物、提取物混合物、植物提取物混合物、提取物组分和/或活性药剂或成分或其组合的在给药到对象(例如哺乳动物例如人类)时,足以在对象中实现治疗例如改善氧化的抑制和/或减轻炎症等的量。本公开的组合物、提取物、植物提取物、提取物混合物、植物提取物混合物、提取物组分和/或活性药剂或成分的构成“有效量”或“治疗有效量”的量,将随着所述活性药剂或化合物、待治疗的病症及其严重程度、给药方式、给药持续时间或待治疗对象的年龄而变,但可以由本领域普通技术人员根据自己的知识和本公开内容常规地确定。
术语“可药用”意味着那些药物、医药、提取物或惰性成分适合于与人类和较低等动物相接触使用而没有过度毒性、不相容性、不稳定性、刺激性等,并与合理的利益/风险比相称。
术语“给药”被定义为通过本领域中已知的途径,包括但不限于静脉内、动脉内、口服、肠胃外、颊、局部、透皮、直肠、肌肉内、皮下、骨内、透粘膜或腹膜内给药途径将组合物提供给对象。在优选实施方式中,给药组合物的口服途径是适合的。
当在本文中使用时,术语“对象”或“个体”包括可能向其给药组合物的哺乳动物。哺乳动物的非限制性实例包括人类、非人类灵长动物、犬科动物、猫科动物、马科动物、牛科动物、啮齿动物(包括转基因和非转基因小鼠)等。在某些实施方式中,所述对象是非人类哺乳动物,并且在某些实施方式中,所述对象是人。
当在本文中使用时,术语“载体”是指有助于将一种或多种植物提取物在适合于给药的形式中维持在可溶且均匀状态下的组合物,其无毒并且不以有害方式与其他组分相互作用。
当在本文中使用时,术语“调节”或“调节物”通常是指间接影响(或调节)一种或多种代谢障碍的物质。
当在本文中使用时,术语“代谢障碍”是指改变正常代谢过程的异常化学反应。代谢障碍的非限制性实例包括葡萄糖代谢障碍、DNA修复缺陷障碍、脂类代谢障碍、吸收不良障碍和钙代谢障碍。此类障碍的症状通常存在于被称为代谢综合征的一系列病症中,包括高血压(血压升高)、腹型肥胖(腰部体脂过多)和血脂异常(胆固醇或甘油三酯水平异常),它们一起发生,提高人们患心脏病、中风和糖尿病的风险。
除非另有指明,否则整个本公开中叙述的所有比例和百分率均以重量计。
本发明提供了一种能够调节一种或多种代谢障碍的基于植物的提取物。更具体来说,本发明针对来自于腰果属的腰果种皮的植物提取物。已发现此类植物提取物能够抑制MMP-9并充当PPAR-γ的激动剂,从而在MMP-9抑制的情况下限制不利的酶活性和/或在充当PPAR-γ的激动剂时促进配体结合。PPAR-γ通过控制由脂肪组织分泌的许多因子例如脂联蛋白、瘦蛋白、抵抗素和肿瘤坏死因子-α(TNF-α)的表达来影响外周组织的胰岛素敏感性。PPAR-γ还可以直接上调4型葡萄糖转运蛋白(Glut4),并因此调节葡萄糖体内平衡。通过限制MMP-9和/或促进PPAR-γ活性,可以减轻一种或多种代谢障碍例如炎症、肿瘤转移和/或胰岛素敏感性。此外,通过限制MMP-9和/或促进PPAR-γ活性,可以减轻代谢综合征的一种或多种症状,包括高血压、肥胖症和/或血脂异常。
根据本发明的能够抑制MMP-9和/或充当PPAR-γ的激动剂的有用植物提取物包括来自于腰果属的植物提取物。更具体来说,所述基于植物的抑制剂是选自Anacardiumhumile、Anacardium othonianum、Anacardium giganteum、Anacardium nanum、Anacardiumnegrense和/或腰果(Anacardium occidentale)的一个或多个物种的植物提取物。优选地,所述植物提取物来自于腰果(Anacardium occidentale Linn)物种。在一个实施方式中,所述植物提取物来自于腰果(Anacardium occidentale)物种的种皮。
根据本发明的能够抑制MMP-9和/或充当PPAR-γ的激动剂的组合物可以包括能够作为活性成分起作用的一种或多种化合物。所述化合物可能是所述植物提取物的组分。例如,所述化合物可以是获得所述植物提取物的植物中存在的植物化学成分。所述化合物可能至少部分负责抑制MMP-9和/或充当PPAR-γ的激动剂。所述化合物可以是能够抑制MMP-9和/或充当PPAR-γ的激动剂的任何化合物。在一个实施方式中,所述化合物选自植物化学成分儿茶素类、表儿茶素类和/或原花青素(例如A、B、三聚体、四聚体)。
通常,植物的一个或多个部位可用于生产植物提取物,包括但不限于根、茎、叶、花、果实、种子和种子的种皮。在本发明中,单独地或与其他植物部位一起至少使用种子的种皮来生产所述植物提取物。来自于腰果属植物的种皮可以从各种不同来源商购。所述腰果种皮的提取物可以使用任何适合的提取技术获得。
就此而言,可以收集并粉碎所述植物的一个或多个部位,特别是所述植物的种皮。然后可以使用适合的溶剂提取所述粉碎的材料。所述溶剂可以在浓缩步骤中除去。例如,可以将所述提取过的材料过筛或过滤,以产生上清液和滤饼。所述滤饼可以被压榨以除去显著部分的液体,所述液体可以添加到所述上清液中。然后可以将所述滤饼脱水并用作纤维来源。所述上清液可以被蒸馏以除去所述溶剂或其一部分,以形成植物提取物液体浓缩物。所述被除去的溶剂可以循环利用。所述浓缩物可以被干燥(例如通过喷雾干燥),以提供干燥的植物提取物。这种干燥的植物提取物可以如本文中所述进行化验和/或标准化。优选地,所述干燥的植物提取物源自于腰果(Anacardium occidentale),特别是腰果(Anacardium occidentale)植物的种皮。
适合用于提取过程的溶剂包括水、醇或其混合物。示例性的醇性溶剂包括但不限于C1-C7醇类(例如甲醇、乙醇、丙醇、异丙醇和丁醇)、水-醇类或醇与水的混合物(例如水性乙醇)、多元醇(例如丙二醇和丁二醇)和脂肪醇。任何这些醇性溶剂可以以混合物的形式使用。在一个实施方式中,所述植物提取物使用乙醇、水或其组合(例如约70%乙醇与约30%水的混合物)来提取。在另一个实施方式中,所述植物提取物仅使用水来提取。
在一个实施方式中,所述植物提取物可以使用有机溶剂提取技术来获得。在另一个实施方式中,可以使用溶剂顺序分离技术来获得所述植物提取物。全水-乙醇提取技术也可用于获得所述植物提取物。通常,这被称为一次性提取。
也可以使用全乙醇提取。这种技术使用乙醇作为溶剂。这种提取技术可以产生除了水溶性化合物之外还具有脂溶性和/或亲脂性化合物的植物提取物。
可用于获得所述植物提取物的提取技术的另一个实例是超临界流体提取(“SFE”)。在这种提取过程中,待提取的材料可以不被暴露于任何有机溶剂。相反,可以使用含有或不含改性剂的处于超临界条件(>31.3℃和>73.8巴)下的二氧化碳作为提取溶剂。本领域技术人员将会认识到,可以改变温度和压力条件以获得提取物的最佳得率。这种技术与全己烷和乙酸乙酯提取技术相似,可以产生脂溶性和/或亲脂性化合物的提取物。
在所述过程中产生的植物提取物可以包括在所述被提取的材料中存在的广泛种类的植物化学成分。所述植物化学成分可以是脂溶性或水溶性的。在收集所述提取物溶液后,可以将溶剂蒸发,得到所述提取物。
所述植物提取物可以被标准化至规定量的特定化合物。例如,所述植物提取物可以被标准化至规定量的所述提取物中存在的活性成分或植物化学成分。在一个实施方式中,所述植物提取物被标准化至以所述提取物的总重量计约15.0重量%或更高的儿茶素含量。
在所述MMP-9抑制剂和/或PPAR-γ激动剂组合物中存在的植物提取物的量可以取决于几种因素,包括所需的MMP-9抑制和/或PPAR-γ活性提高的水平、特定植物提取物或其组分的MMP-9抑制和/或PPAR-γ活性提高的水平和其他因素。优选地,所述植物提取物以所述组合物的总重量计约0.005重量%或更高、例如约0.005重量%至约99.00重量%的量存在。
所述MMP-9抑制剂和/或PPAR-γ激动剂组合物可以包括一种或多种可接受的载体。所述载体可以帮助将所述植物提取物并入到具有适合于给药到对象的形式的MMP-9抑制剂和/或PPAR-γ激动剂组合物中。大量可接受的载体在本领域中是已知的,并且所述载体可以是任何适合的载体。所述载体优选地适合于给药到动物包括人类,并且能够作为载体起作用而不显著影响所述植物提取物和/或任何活性成分的所需活性。所述载体可以在所需的给药途径和所述组合物的剂型的基础上选择。
适合的剂型包括液体和固体形式。在一个实施方式中,所述组合物采取凝胶、糖浆、浆液或悬液的形式。在另一个实施方式中,所述组合物采取液体剂型,例如口服液(drink shot)或液体浓缩物。在另一个实施方式中,所述组合物以固体剂型存在,例如片剂、丸剂、胶囊、糖衣丸剂或粉剂。当采取液体或固体剂型时,所述组合物可以采取适合于掺入到食品中以备递送的食品递送形式。适合用于固体形式(特别是片剂和胶囊形式)中的载体的实例包括但不限于有机和无机惰性载体材料例如明胶、淀粉、硬脂酸镁、滑石、树胶、二氧化硅、硬脂酸、纤维素等。所述载体可以是基本上惰性的。
作为实例,硅化微晶纤维素可用作载体或粘合剂。硅化微晶纤维素是微晶纤维素和胶体二氧化硅的物理混合物。一种此类适合形式的硅化微晶纤维素是可以从PenwestPharmaceutical Co.,Patterson,N.J获得的ProSolv 90。二氧化硅除了由所述硅化微晶纤维素提供的之外,也可以作为加工助剂添加到所述组合物。例如,可以包括二氧化硅作为助流剂,以在固体剂量单元例如片剂的制造中在压片期间改善粉末的流动性。
在另一个实施方式中,所述载体至少是功能性载体例如荞麦或斯佩耳特小麦。通过在所述组合物中添加功能性载体,可以提供额外的益处,例如与例如上文提到的标准载体相比更低的血糖生成指数。此外,功能性载体可以是无过敏原的(例如荞麦),并且通过将它们添加到生产过程中,本发明的植物提取物可能从这些功能性载体的类黄酮例如芸香苷和槲皮苷获益。此外,这些功能性载体的高纤维含量也可以促进并调节肠道通过。最后,斯佩耳特小麦中存在的硒的附加的矿物质益处可能有助于代谢。
所述MMP-9抑制剂和/或PPAR-γ激动剂组合物可以包含其他惰性成分例如润滑剂和/或助流剂。润滑剂有助于制造过程中例如从模具弹出的过程中片剂的操控。助流剂在压片期间改善粉末流动性。硬脂酸是可接受的润滑剂/助流剂的实例。
所述MMP-9抑制剂和/或PPAR-γ激动剂组合物可以被制造成固体剂型例如片剂和胶囊。这种形式提供了可以由个体容易地运输到进餐场所例如餐厅,并在进食食物之前、期间或之后服用的产品。所述组合物可以被配制成含有适量所述植物提取物和/或活性成分的剂量单元,允许个体根据适合的参数例如体重、食物量或碳水化合物(例如糖)含量来确定服用的单元的适合数量。
在一个实施方式中,所述植物提取物以治疗有效量存在于所述组合物中,例如约1.0μg/mL或更高、优选地约1.0μg/mL至约2000.0μg/mL、更优选地约30.0μg/mL至约1000.0μg/mL、甚至更优选地约50.0μg/mL至约500.0μg/mL、甚至更优选地约100.0μg/mL至约250.0μg/mL的量。所述组合物可以作为单剂或在多剂中给药。在一个实例中,所述化合物每天给药至多三剂。例如,所述化合物可以在餐前、餐中或餐后给药。在一个实施方式中,所述组合物是具有MMP-9抑制剂和/或PPAR-γ激动剂性质的膳食补充剂,含有治疗有效量的腰果种皮提取物。
所述剂量可以被选择成在单个单元中提供可能对某些个体和/或某些食品有效的抑制作用水平,同时也允许相对简单的剂量增加,以提供可能对其他个体和/或其他食品有效的其他抑制作用水平。
所述抑制性组合物可以采取适合于口服摄取的形式。这种形式可以被配置成旨在提供规定剂量的所述植物提取物的单一剂型。例如,所述单一剂型可以是粉剂、丸剂、片剂、胶囊或口服液。所述单一剂型可以包含例如约1.0μg/mL至约2000.0μg/mL的所述植物提取物。
实施例
实施例-材料和化学物质剖测
实施例1-使用70%乙醇溶剂的腰果种皮提取物的制备
将干燥的腰果(Anacardium occidentale)种皮粉末(60g)装入3个100ml不锈钢试管中,并使用Thermo ScientificTMDionexTMASE 350加速溶剂提取器在80℃的温度和1500psi的压力下用DI水中的70%乙醇溶剂提取两次。过滤并收集所述提取物溶液。将合并的乙醇提取物溶液用旋转蒸发仪在真空下蒸发,以给出粗品腰果种皮提取物。
提取结果提供在下述表1中。
表1-腰果种皮的提取
植物部位 | 植物粉末(g) | 提取物重量(g) | 提取得率(重量%) |
种皮 | 60 | 23.78 | 39.63% |
实施例2-腰果种皮提取物的儿茶素定量
与带有光电二极管阵列检测器的日立高效液相色谱(“HPLC/PDA”)一起使用C18反相柱(5μm C18(2)LC柱250x 4.6mm,可以从Torrance,California,US获得),来确定所述腰果种皮提取物中存在的游离儿茶素类。对于流动相A来说,溶剂是水中的0.10%磷酸(“H3PO4”),并且对于流动相B来说,溶剂B是乙腈(“ACN”),其被用于以1.0ml/min的流速洗脱,并使用275nm处的UV吸收和35℃的柱温。使用的儿茶素参比标准品来自于Sigma-Aldrich Co。将所述参比标准品溶解在甲醇(“MeOH”):0.1%H3PO4(1:1比例)中,其中儿茶素(C1251)浓度为0.5mg/ml,并且表儿茶素(E1753)浓度为0.1mg/ml。测试样品在容量瓶中以2mg/ml的浓度制备在含有50%MeOH的0.1%H3PO4中,超声处理直至溶解(大约10分钟),然后冷却至室温,充分混合,并通过0.45μm尼龙注射式滤器过滤。通过将20μl样品注射到所述HPLC中进行HPLC分析。下面的表2提供了HPLC分析方法的梯度表。
表2-HPLC分析方法的梯度表
时间(min) | 流动相A | 流动相B |
0.0 | 85.0 | 15.0 |
7.0 | 85.0 | 15.0 |
12.0 | 10.0 | 90.0 |
16.5 | 10.0 | 90.0 |
16.6 | 85.0 | 15.0 |
24.0 | 85.0 | 15.0 |
腰果种皮提取物中HPLC儿茶素的定量结果提供了以所述提取物的总重量计,儿茶素含量为9.40重量%并且表儿茶素含量为6.12重量%,总儿茶素含量为15.52重量%。因此,所述腰果种皮提取物可以被标准化至以所述提取物的总重量计总儿茶素含量为约15.00重量%或更高。腰果种皮提取物在275nm波长处的HPLC色谱图提供在图1中。
实施例3-腰果种皮提取物的化学剖测
使用超高压液相色谱(“HPLC”)和质谱(UPLC I类和GS-XT-QTof系统,两者均可以从Water Corporation,Milford,Massachusetts USA获得),确定了所述腰果种皮提取物中存在的类黄酮化合物。使用的柱是UPLC HSS T32.1x100mm,1.8μm,柱温为40℃,样品温度为15℃。对于流动相来说,溶剂A是含有10%乙腈(“ACN”)的水(含有0.1%甲酸),溶剂B是ACN。采集范围是100-1500道尔顿(“Da”),采集模式是电喷雾电离(“ESI”)(-)。下面的表3提供了HPLC条件。
表3-用于分析腰果种皮提取物的HPLC条件
运行时间(min) | 进样体积(μL) | 浓度 |
20.00 | 2.00 | 1mg/mL |
峰的鉴定仅仅基于准确质量。鉴定到二没食子酰基儿茶素、儿茶素和表儿茶素是腰果种皮提取物的主要组分。在所述提取物中也检测到原花青素类,包括A和B型原花青素、原花青素四聚体和原花青素三聚体,其中B型原花青素是所述原花青素类的主要组分。除了那些刚刚提到的化合物之外,鉴定到的化合物还包括二没食子酰基儿茶素、vaccihein A、6"-对香豆酰基洋李苷和dunalianoside B等。从所述分析获得的腰果种皮提取物的LC/MS和LC/PDA色谱图示出在图2中。
实施例-生物测定法
使用食品级乙醇制备腰果种皮的提取物,然后如上所述过滤和干燥。对于测定法准备的其余部分,使用研究级试剂。将提取物溶解在二甲基亚砜(“DMSO”)中至终浓度为50mg/mL,然后在适合于每种生物测定法的缓冲液中稀释到工作浓度。
实施例4-MMP-9抑制
所述测定使用来自于abcam(Cambridge,United Kingdom;产品号ab139448)的MMP-9抑制剂筛选测定试剂盒(比色)。将腰果种皮提取物在测定缓冲液中稀释,用于在剂量曲线中测试MMP-9抑制,并添加到96孔半体积微孔板的孔中。使用1.3μM的广谱MMP抑制剂NNGH作为阳性对照。将MMP-9酶在测定缓冲液中以1:60稀释并添加到测试孔和阳性和阴性对照中,终浓度为每孔0.9单位。将板在37℃温育30分钟,以允许抑制剂与酶结合。将MMP-9底物在测定缓冲液中以1:25稀释,并以100μM的终浓度添加到孔。然后将所述板在405nm处连续读取吸光度,每分钟获取读数共20分钟。为每个孔计算线性范围(前10分钟)内的斜率,并使用阴性(未处理)对照孔作为100%分数来确定测试化合物和阳性对照的抑制百分数。
参考图3,取决于腰果种皮提取物的浓度,观察到各种不同程度的MMP-9抑制。在约1μg/mL或更高、更特别地约1μg/mL至至少约250μg/mL、甚至更特别地约15μg/mL至约250μg/mL下观察到腰果种皮提取物抑制,并且IC50为123μg/mL。
实施例5-PPAR-γ活化
使用来自于BioVision的PPAR-γ配体筛选/表征测定试剂盒(产品号:K437-100)来测试腰果种皮提取物结合并活化PPAR-γ的能力。这种测定试剂盒依靠测试样品置换与PPAR-γ蛋白结合的荧光探针。当测试样品置换荧光探针并结合到PPAR-γ时,存在着荧光强度的可观察的降低。将PPAR-γ测定探针在DMSO中以1:100稀释。制备PPAR-γ蛋白、PPAR-γ测定探针、PPAR-γ测定缓冲液和DMSO(终浓度为10%)的主混合物,并将其添加到384孔黑色板中的测试样品中,每孔共25μL。将板在室温下温育5分钟,然后在荧光读板器上以下述波长读取:激发-405nm,发射-460nm。在不存在PPAR-γ测定探针或PPAR-γ蛋白的情况下也读取样品,并从实验值中减去这些空白值以校正干扰。抑制百分数被计算为未处理的对照(其具有荧光探针与PPAR-γ蛋白的100%结合)与测试样品之间的荧光强度差除以所述未处理的对照的值,并被表示为百分数。
参考图4,对所述提取物观察到PPAR-γ配体结合活性的各种不同程度的强度。测试了10种不同浓度的腰果种皮提取物(3.9、7.8、15.6、31.2、62.5、125、250、500、1000和2000μg/mL)。在约50.0μg/mL至至少约2000μg/mL、更特别地约100μg/mL至约1000μg/mL、甚至更特别地约125μg/mL至约250μg/mL下观察到腰果种皮提取物活化。对所述腰果种皮提取物观察到IC50为179μg/mL。
上述数据说明腰果(Anacardium occidentale L.)种皮的植物提取物具有一种或多种化合物,所述化合物在解决组织重塑或修复时正常生理状况与不受控制的酶表达/活性之间的失衡中可能有些贡献,即所述提取物表现出一种或多种代谢障碍的调节。
上面的描述公开了本发明的几种方法和材料。本发明易于在材料和方法方面做出修改,并易于在制造方法和设备方面做出改变。对于本领域技术人员来说,考虑到本公开或本文公开的发明的实践,此类修改将变得显而易见。此外,除非另有定义,否则本文中使用的所有技术和科学术语均具有与本发明所属领域的普通技术人员通常理解的相同的含义。因此,本发明不打算限于本文公开的具体实施方式,而是打算覆盖落入随附的权利要求书中体现的本发明的真正范围和精神之内的所有修改和替换方案。
Claims (13)
1.一种组合物,其包含腰果(Anacardium occidentale L.)种皮的植物提取物,其中所述植物提取物表现出一种或多种代谢障碍的调节。
2.根据权利要求1所述的组合物,其中所述植物提取物以约1.0μg/mL或更高的量存在。
3.根据权利要求2所述的组合物,其中所述植物提取物以约1.0μg/mL至约2000.0μg/mL的量存在。
4.根据权利要求1所述的组合物,其中所述组合物还表现出MMP-9抑制。
5.根据权利要求4所述的组合物,其中所述植物提取物以约1.0μg/mL至约2000.0μg/mL的量存在。
6.根据权利要求1所述的组合物,其中所述组合物还表现出PPAR-γ激动剂活性。
7.根据权利要求6所述的组合物,其中所述植物提取物以约50.0μg/mL至约2000.0μg/mL的量存在。
8.一种对一种或多种代谢障碍具有调节性质的膳食补充剂,其包含治疗有效量的腰果种皮提取物。
9.根据权利要求8所述的膳食补充剂,其中所述腰果种皮提取物以约1.0μg/mL或更高的量存在。
10.一种包含儿茶素类的植物提取物,其中所述提取物已被标准化至以所述提取物的总重量计约15.0重量/重量%或更高的儿茶素含量,其中所述植物提取物表现出对一种或多种代谢障碍的调节性质,并且其中所述植物提取物至少包含从腰果属(Anacardium)获得的提取物。
11.根据权利要求10所述的植物提取物,其中所述从腰果属获得的提取物至少是从腰果获得的提取物。
12.根据权利要求11所述的植物提取物,其中所述从腰果获得的提取物至少从腰果种子的种皮获得。
13.一种在对象中调节一种或多种代谢障碍的方法,所述方法包括给药以约1.0μg/mL至约2000.0μg/mL的浓度包含腰果种皮的植物提取物的组合物。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020006444A1 (en) * | 1997-11-28 | 2002-01-17 | Konishi Jin-Emon | Crude drug extracts, and methods for making and standardizing same |
FR2836337A1 (fr) * | 2002-02-28 | 2003-08-29 | Bio Serae Laboratoires | Utilisation des polymeres procyanidoliques a titre d'agents inhibuteurs des alpha-amylases et application dans des compositions a visees dietetiques |
CN101516386A (zh) * | 2006-07-14 | 2009-08-26 | 帝斯曼知识产权资产管理有限公司 | 包含玫瑰果和其它活性剂的用于治疗炎性病症的组合物 |
CN103442691A (zh) * | 2010-09-10 | 2013-12-11 | 玫琳凯有限公司 | 包含拟爱神木和腰果树果肉及其提取物的局部护肤制剂 |
US20140100177A1 (en) * | 2011-06-07 | 2014-04-10 | Centre De Cooperation Internale En Recherche Agronomique Pour Le Developpement | Composition comprising cashew apple extract |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1522082A2 (de) | 2002-07-01 | 2005-04-13 | Rolf Eisenring | Verfahren zur herstellung von superkondensatoren |
DE202008005904U1 (de) * | 2008-04-29 | 2008-07-10 | Day-Med-Concept Gmbh | Kalt geknackte Cashewnuss zur Anwendung in der Therapie |
US7897184B1 (en) | 2009-08-13 | 2011-03-01 | Access Business Group International Llc | Topical composition with skin lightening effect |
US8685472B2 (en) | 2010-03-01 | 2014-04-01 | Access Business Group International Llc | Skin whitening composition containing chia seed extract |
GB201007472D0 (en) | 2010-05-05 | 2010-06-16 | Univ Wales Bangor | Fractionation of cashew nut shell liquid |
US9333159B2 (en) | 2011-04-29 | 2016-05-10 | Photomedex, Inc. | Topical DNA repair composition |
WO2020046478A1 (en) * | 2018-08-31 | 2020-03-05 | Innophos, Inc. | Botanical modulator of metabolic disorders |
-
2019
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- 2019-07-12 CA CA3110954A patent/CA3110954A1/en active Pending
- 2019-07-18 US US16/515,101 patent/US10932485B2/en active Active
-
2021
- 2021-01-26 US US17/158,693 patent/US11297869B2/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020006444A1 (en) * | 1997-11-28 | 2002-01-17 | Konishi Jin-Emon | Crude drug extracts, and methods for making and standardizing same |
FR2836337A1 (fr) * | 2002-02-28 | 2003-08-29 | Bio Serae Laboratoires | Utilisation des polymeres procyanidoliques a titre d'agents inhibuteurs des alpha-amylases et application dans des compositions a visees dietetiques |
CN101516386A (zh) * | 2006-07-14 | 2009-08-26 | 帝斯曼知识产权资产管理有限公司 | 包含玫瑰果和其它活性剂的用于治疗炎性病症的组合物 |
CN103442691A (zh) * | 2010-09-10 | 2013-12-11 | 玫琳凯有限公司 | 包含拟爱神木和腰果树果肉及其提取物的局部护肤制剂 |
US20140100177A1 (en) * | 2011-06-07 | 2014-04-10 | Centre De Cooperation Internale En Recherche Agronomique Pour Le Developpement | Composition comprising cashew apple extract |
Non-Patent Citations (9)
Title |
---|
A.G.MATHEW等: "POLYPHENOLS OF CASHEW KERNEL TESTA", 《JOURNAL OF FOOD SCIENCE》 * |
NEEL CHANDRASEKARA等: "Effect of Roasting on Phenolic Content and Antioxidant Activities of", 《JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY》 * |
VASUDEVA KAMATH等: "Dimethoate induced biochemical perturbations in rat pancreas", 《PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY》 * |
VASUDEVA KAMATH等: "The efficacy of cashew nut (", 《FOOD CHEMISTRY》 * |
丁伟等: "《缺血性脑血管病研究新进展》", 31 July 2009, 中国海洋大学出版社 * |
王霞等: "植物缓蚀剂的制备方法与研究方向", 《表面技术》 * |
陈临溪等: "《细胞信号转导药理与临床》", 31 October 2014, 人民军医出版社 * |
陈宜辉: "《实用临床内科学》", 31 August 2017, 吉林科学技术出版社 * |
陈美娟等: "2型糖尿病并发症相关因子及中药治疗研究进展", 《泸州医学院学报》 * |
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