CN112384232A - 用于预防或治疗黄斑变性的药物组合物和保健功能食品 - Google Patents
用于预防或治疗黄斑变性的药物组合物和保健功能食品 Download PDFInfo
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Abstract
本发明涉及一种组合物和一种保健功能食品,其包括大花紫薇叶提取物、番石榴叶提取物、或其混合物。本发明的提取物抑制由蓝光引起的A2E的光氧化,抑制由蓝光诱导的视网膜色素上皮细胞的死亡,并且在蓝光诱导的黄斑变性的动物模型中抑制对视细胞的外核层的损害,因此,本发明的提取物可以有益地用作用于预防或治疗黄斑变性的组合物,以及用作用于预防或减轻黄斑变性的保健功能食品。
Description
技术领域
本发明涉及用于预防或治疗黄斑变性的药物组合物、和用于预防或减轻黄斑变性的保健功能食品。
背景技术
位于视网膜的中央部分的神经组织称为黄斑。该部分是视细胞非常密集的区域,该部分形成对象的图像,用于提供中央视觉并且有助于视野的清晰度和准确性。由于衰老、紫外线或蓝光造成的损害、遗传因素、基础疾病(糖尿病、血脂异常、高胆固醇血症)、毒性和炎症而导致会发生变性,从而导致视力障碍。这称为黄斑变性。除了白内障、青光眼和糖尿病性视网膜病变以外,黄斑变性也是失明的主要原因之一。当黄斑发生变性时,中央视觉首先受损,导致视力模糊或破碎,如果情况恶化,则会导致严重的失明疾病。
黄斑变性可以分为两种类型:干性(非渗出性)黄斑变性和湿性(渗出性)黄斑变性。干性黄斑变性占全部患有黄斑变性的患者的约90%,并且其特征在于,由于视网膜色素上皮和布鲁赫膜(Bruch’s membrane)之间的称为玻璃疣(drusen)的杂质的累积而导致黄斑组织萎缩或变薄。另一方面,湿性黄斑变性占全部患者的约10%,并且是指由于以下原因而引起的严重视力丧失:由于没有向黄斑提供血液和营养物质而导致新生血管的异常形成,并且其破裂使血液或粘液渗漏进入黄斑。干性黄斑变性的早期迹象是无症状的,或者即使它们是有症状的,也被认为是老花眼,即老年人的视力。因此,这些早期迹象常常被忽略。然而,如果不抑制或治疗干性黄斑变性的进展,则会发生由于持续性视网膜损伤而导致的视力丧失。此外,这会导致湿性黄斑变性并因此导致失明。因此,在早期阶段预防干性黄斑变性是重要的。
干性黄斑变性的主要机制尚不清楚,但会受到各种因素影响。据推测,主要原因可能是视网膜色素上皮细胞的正常功能的丧失。视网膜上皮细胞通常起到吞噬和降解感光细胞的外节(outer segment)的作用,并且还参与视网膜的压力调节和内稳态。感光细胞和视网膜上皮细胞经历视觉回路过程(visual circuit process),从而形成副产物色素A2E(N-视黄基-N-亚视黄基乙醇胺)和脂褐素(脂质和蛋白质的混合物)。视网膜色素上皮细胞可以通过吞噬作用积聚A2E和脂褐素,其中A2E在细胞中积聚而不容易排出。关于视网膜色素上皮细胞的死亡,高浓度的A2E是主要原因。另外,即使在低浓度下,A2E也对UV或蓝光发生光氧化,并且转化成环氧化物形式,例如过氧-A2E(peroxy-A2E)和呋喃-A2E(furano-A2E)。高反应性环氧化物形式的A2E引起炎症反应以及氧化应激,并且改变线粒体的蛋白活性以诱导细胞凋亡。结果,正常视网膜色素上皮细胞的功能的丧失导致感光细胞的继发性死亡。特别地,具有高度集中的感光细胞的黄斑严重受损,从而引起黄斑变性。
同时,番石榴(Psidium guajava)是一种属于桃金娘科的植物,主要分布在亚热带地区,并且产生许多长度为3至7m的分支。番石榴广泛分布于热带和亚热带地区,包括印度、墨西哥南部和南美。番石榴叶中的多酚含量高,并且已知对糖尿病、心血管疾病、癌症和传染病有效。
大花紫薇(Banaba)(Lagerstroemia speciosa)是一种属于Buddha科的落叶热带植物,其根和叶用作食物。大花紫薇广泛分布于热带和亚热带地区,包括印度、中国南部、缅甸和菲律宾。叶子是椭圆形的,长18cm且宽6cm,并且含有大量的科罗索酸。已知大花紫薇叶对糖尿病、肥胖、传染病、癌症等有效,特别是具有抗氧化和抗炎活性。
因此,在使用已经长期使用并且对人类安全的天然材料开发用于黄斑变性的治疗剂的同时,本发明人发现番石榴叶和大花紫薇叶提取物抑制由于蓝光引起的A2E的光氧化,抑制蓝光诱导的视网膜色素上皮细胞的死亡,并且在患有蓝光诱导的黄斑变性的动物模型中进一步防止对视细胞的外核层的损害,因此,基于以上发现完成了本发明。
发明内容
发明要解决的问题
本发明的目的是提供用于预防或治疗黄斑变性的药物组合物、和用于预防或减轻黄斑变性的保健功能食品。
用于解决问题的方案
1.一种用于预防或治疗黄斑变性的药物组合物,其包括大花紫薇叶提取物或番石榴叶提取物。
2.根据上述1的药物组合物,其中用于提取物的提取溶剂包括水和C1至C4醇中的至少一种。
3.根据上述1的药物组合物,其中用于提取物的提取溶剂包括甲醇和乙醇中的至少一种。
4.根据上述1的药物组合物,其中该组合物包括大花紫薇叶提取物和番石榴叶提取物。
5.一种用于预防或减轻黄斑变性的保健功能食品,其包括大花紫薇叶提取物或番石榴叶提取物。
6.根据上述5的保健功能食品,其中用于提取物的提取溶剂包括水和C1至C4醇中的至少一种。
7.根据上述5的保健功能食品,其中用于提取物的提取溶剂包括甲醇和乙醇中的至少一种。
8.根据上述5的保健功能食品,其中该保健功能食品包括大花紫薇叶提取物和番石榴叶提取物。
发明的效果
本发明的提取物抑制由于蓝光引起的A2E的光氧化,抑制由蓝光诱导的视网膜色素上皮细胞的死亡,并且在患有蓝光诱导的黄斑变性的动物模型中防止对视细胞的外核层的损害,因此,本发明的提取物可以有益地用作用于预防或治疗黄斑变性的组合物、或者用于预防或减轻黄斑变性的保健功能食品。
附图说明
图1是示出番石榴叶、大花紫薇叶、及其混合物经时(分钟)抑制由于蓝光引起的A2E光氧化的效果的图。
图2是示出番石榴叶、大花紫薇叶、及其混合物在特定时间段(3分钟)抑制由于蓝光引起的A2E光氧化的效果的图。
图3是示出番石榴叶、大花紫薇叶、其混合物、和叶黄素抑制视网膜色素上皮细胞的死亡的效果的图(###:相对于对照(P<0.001),a:对蓝光照射组(P<0.001),b:对混合物(P<0.001),c:对叶黄素(P<0.05))。
图4是示出用于确认番石榴叶、大花紫薇叶、及其混合物的预防和治疗黄斑变性的效果的动物实验方案的图。
图5是示出在患有蓝光诱导的黄斑变性的动物模型中,番石榴叶、大花紫薇叶、其混合物、和叶黄素防止对视细胞的外核层(ONL)的损害的效果的图。
图6是定量地示出在患有蓝光诱导的黄斑变性的动物模型中,番石榴叶、大花紫薇叶、其混合物、和叶黄素防止对视细胞的外核层(ONL)的损害的效果的图(###:相对于对照(P<0.001),a:对蓝光照射组(P<0.001),b:对混合物(P<0.01),c:对叶黄素(P<0.05))。
具体实施方式
在下文中,将详细描述本发明。
本发明提供用于预防或治疗黄斑变性的药物组合物和保健功能食品,其包括大花紫薇叶提取物或番石榴叶提取物。
黄斑变性包括干性黄斑变性和湿性黄斑变性两者。
提取大花紫薇叶或番石榴叶的方法没有特别限制,并且可以包括本领域中通常使用的任何提取方法。提取方法的实例包括热水提取、超声提取、过滤、和回流提取等,并且可以通过上述方法中的单独任意一种或以其两种以上的组合来进行提取,但不限于此。
用于提取大花紫薇叶或番石榴叶的溶剂没有特别限制,并且可以包括本领域中通常使用的溶剂。用于提取的水溶性溶剂可以包括例如选自由水和C1至C4醇组成的组中的至少一种,或者两种以上不同溶剂的混合物。
大花紫薇叶提取物或番石榴叶提取物可以以例如10至90重量份、并且优选25至75重量份的量存在于组合物中。
大花紫薇叶提取物或番石榴叶提取物在预防或治疗黄斑变性方面显示优异的效果。更具体地,大花紫薇叶提取物或番石榴叶提取物抑制由于蓝光引起的A2E的光氧化,抑制由蓝光诱导的视网膜色素上皮细胞的死亡,并且在患有蓝光诱导的黄斑变性的动物模型中防止对视细胞的外核层的损害。因此,这些提取物可以用于预防或治疗黄斑变性。
该组合物可以单独包括大花紫薇叶提取物或番石榴叶提取物,但是,在实现预防或治疗黄斑变性的协同作用的方面,该组合物优选以相对于彼此合适的比例包括大花紫薇叶提取物和番石榴叶提取物的混合物。
混合物中大花紫薇叶提取物和番石榴叶提取物的各自的重量比可以为例如1:1/3至3,优选1:0.5至2。
在包括上述提取物的预防性组合物或药物组合物中,术语“治疗”是指通过给予提取物或包含其的组合物来改善或有利地改变黄斑变性的症状的任何行为。参照由韩国医学会(Korean Medical Association)等提供的数据,本发明所属领域的技术人员可以理解本发明的提取物或组合物对疾病有效的确切标准,因此,将确定疾病的减轻、改善和/或治疗的程度。
另外,术语“预防”是指通过给予提取物或包含其的组合物来抑制或延迟黄斑变性的发作的任何行为。对本领域技术人员将显而易见的是,对黄斑变性具有治疗效果的本发明的提取物或组合物在初期症状出现期间或出现之前服用可以预防此类疾病。
本发明的组合物可以同时给药或序贯给药,并且提取物的混合物可以单独给药,或者与其它用于治疗黄斑变性的药物活性成分组合给药。
本发明的组合物可以进一步包括通常用于药物组合物的制造的赋形剂,例如合适的载体、稀释剂、防腐剂、稳定剂、润湿剂、乳化剂、增溶剂、甜味剂、着色剂、渗透压调节剂、和抗氧化剂等。具体地,可以列举乳糖、葡萄糖、蔗糖、山梨糖醇、甘露醇、木糖醇、赤藓糖醇、麦芽糖醇、淀粉、阿拉伯胶、藻酸盐、明胶、磷酸钙、硅酸钙、纤维素、甲基纤维素、微晶纤维素、聚乙烯吡咯烷酮、水、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石、镁、硬脂酸盐、矿物油等。
可以根据制剂容易地选择根据本发明的组合物的给药方法,并且可以通过各种途径将该组合物给药至例如家畜和人等哺乳动物。例如,可以将组合物配制成散剂、片剂、丸剂、颗粒剂、糖衣片、硬或软胶囊、液体制剂、乳剂、混悬剂、糖浆、酏剂、外用制剂、栓剂、和无菌注射用溶液等形式,并且用于口服或肠胃外给药,特别优选口服给药。
用于口服给药的固体制剂包括片剂、丸剂、散剂、颗粒剂、胶囊剂等,并且可以通过向本发明的组合物中添加至少一种赋形剂,例如淀粉、碳酸钙、蔗糖或乳糖、明胶等来制备此类固体制剂。除了简单的赋形剂以外,还使用润滑剂,例如硬脂酸镁、滑石等。用于口服给药的液体制剂包括混悬剂、溶液剂、乳剂、糖浆等,并且除了例如水和液体石蜡等通常使用的简单稀释剂以外,还可以包括各种赋形剂,例如润湿剂、甜味剂、香料和防腐剂。
用于肠胃外给药的制剂包括例如无菌水溶液剂、非水溶剂、混悬剂、乳剂、冻干制剂和栓剂。作为非水溶剂和混悬剂溶剂,可以使用丙二醇、聚乙二醇、例如橄榄油等植物油、和例如油酸乙酯等可注射酯等。作为栓剂的基质,可以使用维比索尔(witepsol)、聚乙二醇、吐温61、可可脂、月桂精酯(laurin butter)、甘油、和明胶等。
此外,包含本发明的组合物的药物组合物可以优选使用本领域已知的任意适当的方法、或者在Remington’s Pharmaceutical Science,Mack Publishing Company,Easton,PA中公开的方法来配制。
根据本发明的组合物的剂量可以取决于患者的体重、年龄、性别和健康状况、饮食、给药时间、给药方法、排泄率和疾病的严重性等而变化,并且可以根据不同的情况而改变。给药频率可以是在期望的范围内每天一次或数次,并且给药时间没有特别限制。另外,本发明的组合物除了原样口服给药以外,通常可以通过将该组合物添加到任何食物中来摄入。此时,要添加的组合物的含量可以根据目的来确定,并且通常在基于食物总重量为0.01至90重量份的范围内。
包含上述用于预防或治疗黄斑变性的提取物的保健功能食品的形式和类型没有特别限制,但是可以以片剂、胶囊剂、散剂、颗粒剂、液体制剂、和丸剂等形式配制和加工。
本发明的保健功能食品是指根据保健功能食品法(Health Functional FoodsAct)第6727号法案,使用具有对人体有用的功能特性的原料或成分制造和加工的食品,并且可以意指为了获得对于保健用途有益的效果例如控制人体的结构和功能所需的营养物质或生理作用而摄取的食品。
本发明的保健功能食品可以包括任意常规的食品添加剂。在本文中,除非另有说明,否则根据食品和药物管理局批准的食品添加剂通则(General Regulations of theFood Additives)和通用试验方法(General Test Methods),基于相应项目的标准和准则判断作为食品添加剂的适用性。
食品添加剂通则中列出的项目包括例如:例如酮、甘氨酸、柠檬酸钙、烟酸和肉桂酸等化合物;例如柿子颜料(persimmon color)、甘草提取物、结晶纤维素、高色颜料(highcolor pigment)和瓜尔豆胶等天然添加剂;以及例如L-谷氨酸钠制剂、面条用碱性添加剂、防腐制剂和焦油着色制剂等混合制剂,但不限于此。
例如,可以通过以下方法来生产片剂形式的保健功能食品:将肽与赋形剂、粘合剂、崩解剂和其它添加剂混合以制备混合物,以任意常规的方式将混合物制粒,然后向其中添加润滑剂并压制成形,或者直接将混合物压制成形。此外,片剂形式的保健功能食品可以根据需要含有增味剂等。
在胶囊形式的保健功能食品中,可以通过用肽和例如赋形剂等添加剂的混合物填充通常的硬胶囊来生产硬胶囊制剂,并且可以通过用肽和例如赋形剂等添加剂的混合物填充例如明胶等胶囊基质来生产软胶囊制剂。软胶囊制剂可以根据需要进一步包含例如甘油或山梨糖醇等增塑剂、着色剂、和防腐剂等。
丸剂形式的保健功能食品可以通过根据任意已知的方法将肽和赋形剂、粘合剂、崩解剂等的混合物成形来生产,并且可以根据需要用白糖或其它包衣剂来包衣。可选地,食品的表面可以用例如淀粉和滑石等特定的材料来包衣。
颗粒剂形式的保健功能食品可以通过根据已知的方法将肽和赋形剂、粘合剂、崩解剂等的混合物制粒来生产,并且可以根据需要包含调味剂和增味剂等。
保健功能食品可以是饮料、肉、巧克力、食物、糕点、比萨、拉面、其它面条、口香糖、糖果、冰淇淋、酒精饮料、复合维生素和膳食补充剂。
在下文中,将通过实施例的方式更详细地描述本发明。
实施例1.各提取物及其混合物的制备
1.番石榴叶提取物的制备
干燥的番石榴叶粉末(100%,印度)购自Phytotech Extracts Pvt Ltd。将干燥的粉末以100g/1L的比例在100℃的蒸馏水中进行提取2小时。将提取的浓缩物过滤,使用旋转浓缩器浓缩,然后冻干以制备本发明的番石榴叶提取物。
2.大花紫薇叶提取物的制备
干燥的大花紫薇叶粉末(100%,印度尼西亚)购自Sambo food。将干燥的粉末以100g/1L的比例用醇进行提取。将提取的浓缩物过滤,使用旋转浓缩器浓缩,然后冻干以制备本发明的大花紫薇叶提取物。
3.上述提取物的混合物的制备
将番石榴叶提取物和大花紫薇叶提取物以1:1的重量比混合以获得混合物。
实施例2.各提取物或其混合物对蓝光的A2E光氧化抑制能力的分析
1.各提取物或其混合物对蓝光的A2E光氧化抑制能力的分析
(1)实验方法
在将100μL的A2E(终浓度为100μM)添加至96孔板后,分别将对照、番石榴叶提取物、大花紫薇叶提取物、及其混合物(终浓度为50、100μg/ml)溶解在蒸馏水中,然后将100μL的各溶液添加至板上的A2E溶液。
此外,添加100μL磷酸盐缓冲盐水(PBS)以校准提取物本身的吸光度,然后分别添加100μL的番石榴叶提取物、大花紫薇叶提取物、及其混合物(最终浓度为50、100μg/ml)。然后,在使用ELISA酶标仪测量在430nm波长(A2E吸收波长)处的吸光度后,用蓝光(4,000lux)照射溶液30秒、1分钟、3分钟、5分钟、8分钟和12分钟,然后测量吸光度。在从测得的吸光度值中减去各样品的固有吸光度值后,使用A2E标准曲线来计算浓度。
(2)实验结果
参照图1,可以确认包括未处理样品的对照(CTL)的未氧化的A2E的量由于A2E的氧化而相对于蓝光的照射时间在1分钟降低至约50%,在3分钟降低至约28.5%,并且在12分钟降低至约12.5%。另一方面,可以确认分别用浓度为50和100μg/ml的大花紫薇叶提取物、番石榴叶提取物、及其混合物处理的组与对照相比具有显著抑制A2E的光氧化的趋势。
参照图1,未氧化的A2E的量的顺序为混合物100>番石榴叶100>混合物50>番石榴叶50≥大花紫薇叶100>大花紫薇叶50>CTL,其中各数值表示浓度(μg/ml)。
参照图2,当比较在蓝光照射1分钟后的A2E光氧化保护效果时,可以看到,与未用蓝光照射的对照相比,蓝光照射组中的未氧化A2E的量减少了约50%。另一方面,可以看出,分别用浓度为50和100μg/ml的大花紫薇叶、番石榴叶、及其混合物处理的组的未氧化A2E量与对照相比分别减少了43%、39%、35%、30%、33%、27%。
实施例3.各提取物及其混合物对蓝光诱导的光氧化的视网膜色素上皮细胞保护
能力的分析
1.各提取物及其混合物对蓝光诱导的光氧化的视网膜色素上皮细胞保护能力的分析
(1)实验方法
由于已知当用蓝光照射积聚有A2E的视网膜色素上皮细胞时会发生光氧化并且引起细胞凋亡,因此,确认使用大花紫薇叶提取物、番石榴叶提取物、及其混合物是否可以抑制在ARPE-19细胞中积聚20μM的A2E后由于用蓝光照射产生的细胞毒性。
具体地,将所有ARPE-19细胞用浓度为20μM的A2E处理24小时,然后分别用实施例1中的100μg/mL的大花紫薇叶提取物、番石榴叶提取物、及其混合物,或者用17.04μg/mL(30μM)叶黄素处理24小时。之后,用蓝光(4,000lux)照射经处理的细胞10分钟。蓝光照射后24小时,通过细胞计数试剂盒-8(cell counting kit-8)(Dojindo Labs,日本)测量ARPE-19细胞的细胞活力,并且确定各处理组的细胞活力相对于未用蓝光照射的对照的百分比(%)。将叶黄素用作阳性对照。
(2)实验结果
参照图3,可以看出,与未用蓝光照射的对照相比,蓝光照射组的细胞活力显著降低(P<0.001),从而引起细胞死亡(细胞凋亡)。通过将未用蓝光照射的对照与蓝光照射组之间的细胞活力之差设为100%,通过借助蓝光照射组和处理组之间的细胞活力之差计算细胞保护效果,来估计各提取物的细胞保护效果。结果,在细胞活力方面,叶黄素具有48.4%的细胞保护效果,而大花紫薇叶提取物具有56.7%的细胞保护效果。同样,番石榴叶提取物具有63.6%的细胞保护效果,而上述提取物的混合物具有75.2%的细胞保护效果。这表明用该混合物、番石榴叶提取物和大花紫薇叶提取物处理的组与叶黄素17.04μg/mL(30μM)处理组相比具有更好的细胞保护效果,并且也表明番石榴叶提取物和大花紫薇叶提取物的混合物与单独的番石榴叶提取物或单独的大花紫薇叶提取物相比显示更优异的保护效果。
实施例4.各提取物及其混合物的蓝光诱导的黄斑变性抑制能力的分析
1.各提取物及其混合物的蓝光诱导的黄斑变性抑制能力的分析
(1)实验方法
使Balb-c小鼠(5周龄,雄性)适应环境并饲养2天,然后每天一次分别口服给予大花紫薇叶提取物、番石榴叶提取物、其混合物、或叶黄素(50mg/kg),持续7天。然后,在黑暗适应24小时后,口服给予各提取物、混合物、以及叶黄素,持续14天,并且每天在给药30分钟后,以10,000lux进行蓝光照射1小时。在蓝光照射和提取物给药结束后24小时,将小鼠处死以取出眼球,然后通过组织染色确定视网膜细胞保护效果(图4)。
将取出的眼球组织用中性缓冲福尔马林溶液固定。将经固定的眼球用流水洗涤,并且使用醇进行脱水处理。此后,使用二甲苯进行透明化处理,并且使用石蜡赋予组织适当的刚性。将眼球制成预定形状的石蜡块,然后切成4μm的厚度。对切开的眼球进行苏木精和曙红(H&E)染色。在使用苏木精进行优先处理后,将眼球在室温下放置30秒,然后用流水洗涤10分钟。之后,使用曙红将眼球处理1分钟。使用显微镜(Olympus Optical,东京,日本)在距离视神经600至900μm的位置观察染色的器官。然后,通过Image J软件(NationalInstitute of Health,Starkville,MD,美国)测量视细胞的外核层(ONL)的厚度,然后对核的数量进行计数。
(2)实验结果
参照图5和图6,作为测量视细胞的ONL的厚度的结果,与未用蓝光照射的对照相比,蓝光照射组的ONL厚度减少了42%(P<0.001)。可以看出,与未用蓝光照射的对照相比,分别给予大花紫薇叶提取物、番石榴叶提取物、其混合物、或叶黄素的组具有显著增加的ONL厚度。通过将未用蓝光照射的对照与蓝光照射组之间的ONL厚度的差设为100%,通过借助蓝光照射组与处理组之间的ONL厚度的差计算ONL保护效果,来估计各给药组的由蓝光引起的ONL厚度保护效果。结果,在ONL厚度方面,可以看出叶黄素给药组具有28.2%的ONL保护效果,而给予大花紫薇叶提取物、番石榴叶提取物、及其混合物的组分别显示39.0%、47.6%和60.9%的ONL保护效果。
在蓝光诱导的黄斑变性模型中,以上结果表明,大花紫薇叶提取物、番石榴叶提取物、及其混合物具有以优于叶黄素的水平显著修复视网膜细胞损伤的效果。此外,以上结果表明,与单独的大花紫薇叶提取物或单独的番石榴叶提取物相比,大花紫薇叶提取物和番石榴叶提取物的混合物具有更好的对视网膜细胞损伤的保护效果。
Claims (8)
1.一种用于预防或治疗黄斑变性的药物组合物,其包括大花紫薇叶提取物或番石榴叶提取物。
2.根据权利要求1所述的药物组合物,其中用于所述提取物的提取溶剂包括水和C1至C4醇中的至少一种。
3.根据权利要求1所述的药物组合物,其中用于所述提取物的提取溶剂包括甲醇和乙醇中的至少一种。
4.根据权利要求1所述的药物组合物,其中所述组合物包括所述大花紫薇叶提取物和所述番石榴叶提取物。
5.一种用于预防或减轻黄斑变性的保健功能食品,其包括大花紫薇叶提取物或番石榴叶提取物。
6.根据权利要求5所述的保健功能食品,其中用于所述提取物的提取溶剂包括水和C1至C4醇中的至少一种。
7.根据权利要求5所述的保健功能食品,其中用于所述提取物的提取溶剂包括甲醇和乙醇中的至少一种。
8.根据权利要求5所述的保健功能食品,其中所述保健功能食品包括所述大花紫薇叶提取物和所述番石榴叶提取物。
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KR20200006203A (ko) | 2020-01-20 |
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EP3821899A1 (en) | 2021-05-19 |
CN112384232B (zh) | 2023-11-07 |
JP2021530460A (ja) | 2021-11-11 |
KR102079742B9 (ko) | 2022-12-08 |
EP3821899A4 (en) | 2022-05-04 |
US20210228670A1 (en) | 2021-07-29 |
KR102079742B1 (ko) | 2020-02-21 |
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