CN111093397A - 一种抗衰老剂以及抗衰老方法 - Google Patents
一种抗衰老剂以及抗衰老方法 Download PDFInfo
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- CN111093397A CN111093397A CN201880060021.9A CN201880060021A CN111093397A CN 111093397 A CN111093397 A CN 111093397A CN 201880060021 A CN201880060021 A CN 201880060021A CN 111093397 A CN111093397 A CN 111093397A
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- aging
- hormone
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Abstract
[课题]提供一种抗衰老剂和抗衰老方法,该抗衰老剂和方法在长期摄取中是安全的,并且能够有效抑制衰老的进展。[解决方案]作为活性成分而含有烟酰胺单核苷酸。
Description
技术领域
本发明涉及一种抗衰老剂以及抗衰老方法。
背景技术
由于例如医学的发展和公共卫生的改善,人的寿命已经稳定地增加。根据最近的报告,预计2060年,在日本,男性的平均寿命将是84.19岁,而女性的平均寿命是90.93岁,超过了90岁。据报道,在日本,65岁以上的人口占总人口的百分比(老龄率)的百分比约为25%,并且老龄化社会正在快速进展。预计老龄率将随着平均寿命的上升而继续上升,并且老龄化社会将进一步继续。
同时,作为日本的老龄化社会面临的问题之一,指出的是,与平均寿命的延长相比,日常生活不受限制的健康寿命的延长较短,并且平均寿命和健康寿命之间的差异正在变大。虽然衰老是任何生物都不能避免的现象,但是每个人都期望延迟衰老,哪怕只是稍微延长,并且延长健康寿命,从而健康长寿。
为了解决老龄化社会中的这种问题,最近,已经积极地进行了在抗衰老医学领域中的研究,其认为衰老是一种疾病并且试图通过治疗来延缓衰老到来本身。抗衰老医学覆盖较宽的区域,例如,内分泌、代谢、动脉硬化、营养、运动器官和感觉器官等,受试者不仅是老年人,而是面向所有年龄,目标是在具有比人们的当前年龄更年轻的身体功能的状态下延长人们的健康时间。
通常,衰老被理解为细胞数量随衰老而降低,并且身体的、生理的和心理的功能下降的现象。在达到成熟阶段后,由于衰老而导致的身体变化在约40岁时开始,显示例如皮肤皱纹、头发、牙齿的脱落、视力、听力的降低、运动功能的下降以及骨量的降低。虽然衰老本身不是疾病,但身体和生理功能的下降增加了所谓的老年病,例如动脉硬化、骨质疏松症、白内障等的风险,并且随着身体功能的衰退引起诸如记忆、学习的心理功能的衰老。
在抗衰老医学领域,关于衰老的研究在很多方面得到了推进;其结果是,关于引起衰老的原因提出了若干假设,如下所示。然而,所有这些都是假想的水平,并且目前没有被完全阐明。
1)基因编程理论
认为,称为端粒的部分位于携带基因信息的染色体的末端,用于在细胞分裂期间正确复制和传递基因信息,每次细胞分裂就会变短,当端粒缩短至一定程度导致端粒功能障碍,这导致细胞的再生降低进而组织的功能下降。即,细胞分裂的次数受端粒限制;当细胞分裂变得不可能时,活体的活性不可避免地丧失,导致衰老。
2)DNA损伤理论
认为,当DNA因诸如紫外线和大气污染物等的刺激而受损并且在损伤被修复之前发生细胞分裂,受损和恶化的信息蓄积导致衰老。虽然受损的DNA被不断修复,但随着年龄增加,修复率降低。
3)活性氧理论
认为,当在活体内未被使用的氧的一部分变成活性氧并氧化细胞时,氧化的细胞不能正常工作,导致衰老的进展。据指出,容易产生活性氧的原因包括例如暴露于紫外线、压力、吸烟和大气污染环境、富含脂肪的饮食和许多添加剂的饮食习惯等。
4)激素理论
认为,与年龄成比例地,特定激素的分泌,例如与代谢控制相关的“生长激素”,与睡眠相关的“褪黑激素”,与男性和女性生殖分别相关的“性激素”减少,导致与那些激素的相应的生理功能的损失和衰老的进展。
5)免疫功能理论
认为,随着衰老,相对于外来病原体的免疫功能下降和过度的炎症反应倾向的发作导致代谢和细胞再生的下降,加速衰老。关于随着衰老而免疫功能下降的原因,指出了与胸腺萎缩的关系。胸腺是用于T细胞分化、增殖和免疫应答表现的中心器官,并且已知随着衰老而萎缩。
根据以往的研究,改善日常生活方式,具有平衡的饮食习惯,并且进行适度的锻炼对于抑制衰老的进展和保持年轻的健康状态是重要的。其中,关于饮食习惯,近年来,有效抑制衰老的食品成分通常是已知的;例如,作为抑制大脑衰老的食品成分,已知二十二碳六烯酸(DHA)、二十碳五烯酸(EPA)、B族维生素(B6、B12、叶酸)、卵磷脂、胆碱和色氨酸;作为增强免疫力的食品成分,已知维生素A、维生素E、维生素C、B族维生素(泛酸、B6、B12、叶酸)和锌;作为增加骨量的食品成分,已知钙、蛋白质、维生素D和维生素K;作为去除活性氧的食品成分,已知类胡萝卜素(番茄红素、叶黄素、维生素A等)、虾青素、多酚(类黄酮、儿茶素、异黄酮、芝麻素、姜黄素等)、维生素E、维生素C、辅酶Q等。另一方面,已知消除活性氧的酶、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶、过氧化氢酶等。
近年来,已经开发了用于抗衰老的新的抗衰老剂。例如,作为可以抑制皮肤衰老的抗衰老剂,特别是可以改善皮肤的色素沉着的抗衰老剂,而报道了包括选自由(A)抗坏血酸2-葡糖苷及其盐构成的群组中的至少一种,以及选自由(B)腺嘌呤、腺苷、腺苷2’-单磷酸,腺苷3’-单磷酸、腺苷5’-单磷酸、环腺苷3’,5’-单磷酸、腺苷5’-二磷酸、腺苷5’-三磷酸及其盐构成的群组中的至少一种的抗衰老剂(专利文献1)。
作为其它实施例,报道了具有以下特征的抗衰老剂,用水对褐藻类的马尾藻属的铜藻(Sargassum horneri)进行提取,在该提取处理过程中将通过使用纤维素酶的酶处理获得的提取物作为活性成分而进行配合(专利文献2)。
现有技术文献
专利文献
专利文献1:日本特许第4129574号公报
专利文献2:日本特许第4926448号公报
发明内容
发明所要解决的问题
本发明的目的是提供一种抗衰老剂和抗衰老方法,其抑制了衰老的进展,并且有效地恢复年轻并且长期摄取是安全的。
解决问题的手段
为了解决上述问题,本发明人进行了认真研究,发现作为辅酶NAD(烟酰胺腺嘌呤二核苷酸)生物合成中涉及的中间代谢物的烟酰胺单核苷酸,具有优异的抗衰老效果。从而完成了本发明。
本发明如下所示。
[1]一种抗衰老剂,含有烟酰胺单核苷酸作为活性成分。
[2]根据[1]所述的抗衰老剂,其中所述抗衰老剂用于改善皮肤的衰老症状、干皮、皮肤瑕疵、雀斑或粗糙皮肤。
[3]根据[1]所述的抗衰老剂,其中所述抗衰老剂用于改善激素分泌。
[4]根据[3]所述的抗衰老剂,其中所述激素是选自生长激素、甲状腺激素、肾上腺皮质激素、性激素、催乳激素、抗利尿激素、甲状旁腺激素和褪黑激素中的一种或两种以上。
[5]根据[1]所述的抗衰老剂,其中所述抗衰老剂用于降低活体内的活性氧。
[6]根据[1]至[5]中任一项所述的抗衰老剂,其中所述抗衰老剂是用于抗衰老的食品。
[7]根据[1]至[5]中任一项所述的抗衰老剂,其中所述抗衰老剂是用于抗衰老的药品。
[8]一种抗衰老方法,所述方法包括使受试者摄取有效剂量的烟酰胺单核苷酸,所述受试者需要有效剂量的烟酰胺单核苷酸(排除对人的医学治疗)。
发明效果
本发明具有优异的抗衰老效果。本发明可以确保视觉功能的有效改进。本发明作为活性成分而含有作为活体内NAD+的生物合成中涉及的中间代谢物的烟酰胺单核苷酸,因此是安全的。本发明可以确保长期摄取。
附图说明
[图1]是表示烟酸(烟酰胺和烟酸的总称)中所涉及的代谢途径的说明图。
[图2a]是表示当烟酰胺单核苷酸被口服施用给受试者24周时,全部受试者的血液褪黑激素浓度的转变的图。
[图2b]是表示当烟酰胺单核苷酸被口服施用给受试者24周时,男性受试者的血液褪黑激素浓度的转变的图。
[图2c]是表示当烟酰胺单核苷酸被口服施用给受试者24周时,女性受试者的血液褪黑激素浓度的转变的图。
[图3a]是表示当烟酰胺单核苷酸被口服施用给受试者24周时,全部受试者至24周时的血液褪黑激素浓度的变化率(%)的图。
[图3b]是表示当烟酰胺单核苷酸被口服施用给受试者24周时,男性受试者至24周时的变化率(%)的图。
[图3c]是表示当烟酰胺单核苷酸被口服施用给受试者24周时,女性受试者至24周时的变化率(%)的图。
具体实施方式
本发明的抗衰老剂含有烟酰胺单核苷酸作为活性成分,提供抗衰老效果。在本发明中,“抗衰老”具有更广泛的含义,包括例如衰老现象的改善、衰老的延迟和回复青春,除了在狭义上的抗衰老之外,还包括诸如使伴随年龄增长的身体功能、生理功能、心理功能的衰退得到抑制、改善、延迟、回复青春、正常化等的一切。具体地,“抗衰老”是指针对下述问题的抑制、改善和延迟等的效果,例如皮肤的衰老症状(皱纹、松垂的发生、皮肤张力的丧失等)、因衰老导致的干皮(皮肤的保湿性降低)、皮肤瑕疵、雀斑、粗糙皮肤、激素(生长激素、甲状腺激素、肾上腺皮质激素、性激素、催乳激素、抗利尿激素、甲状旁腺激素、褪黑激素等)的分泌的减少和增加、由活性氧导致的细胞(脑细胞、心肌细胞等)的损害、头发和牙齿的脱落、视力和听力的下降、运动功能的下降、骨量的降低、体力的降低、记忆力的下降、学习能力的下降、免疫功能的下降和老年病的发生等。
关于为什么含有烟酰胺单核苷酸作为活性成分能够提供这样的效果的详细原因正在进行研究。然而,可以想到的主要原因之一是烟酰胺单核苷酸促进以NAD+依赖性脱乙酰酶Sirt1和Sirt3为代表的“sirtuin(长寿蛋白)”,其结果是,使诸如葡萄糖耐受、生长激素和皮质醇等的激素分泌系统正常化。以下对本发明进行详细说明。
烟酰胺单核苷酸(化学式:C11H15N2O8P)是在包括人在内的许多生物的体内产生的化合物,用以下的式(1)表示。烟酰胺单核苷酸通常被称为NMN,并且作为辅酶NAD+的生物合成中涉及的中间代谢物而被人们知晓。
作为抗衰老剂的活性成分的烟酰胺单核苷酸在NAD在生物体内,由肝脏组织在代谢途径,即在涉及经由犬尿氨酸途径由喹啉酸合成烟酰胺腺嘌呤二核苷酸(NAD)的途径中产生。参照图1对此进行具体描述1。图1是表示作为维生素B3而被人们知晓的烟酸(烟酰胺和烟酸的总称)中所涉及的代谢途径的说明图。通过膳食摄取的烟酸被肝脏吸收,转化为烟酰胺,烟酰胺通过血流被供给到全身。各细胞从血液中吸收烟酰胺,并将其转化为NAD和NADP而使用它们。烟酰胺也可由色氨酸生物合成。
如图1所示,在生物体内,当色氨酸是起始物质时,色氨酸经由作为色氨酸代谢途径的犬尿氨酸途径被转化为喹啉酸(QA),并进一步转化为烟酸单核苷酸(NaMN)。同时,当烟酸(Na)为起始物质时,烟酸直接转化为NaMN。然后,NaMN经由烟酸腺嘌呤二核苷酸(NaAD)通过NAD循环被相互转化为NAD、烟酰胺(NaM)和烟酰胺单核苷酸。烟酰胺(NaM)被烟酰胺磷酸核糖基转移酶(NAMPT)转化为烟酰胺单核苷酸,接着烟酰胺单核苷酸被烟酰胺单核苷酸转移酶(NMNAT)转化以产生NAD。另外,烟酰胺单核苷酸也可由作为NAD中间代谢物的烟酰胺核苷(NR)产生。
烟酰胺单核苷酸包括两种类型即α-形和β-形作为光学异构体,并且在本发明中使用β-形。烟酰胺单核苷酸是通过例如从烟酰胺和核糖合成烟酰胺核苷(参见Bioorg.Med.Chem.Lett.,12,1135-1137(2002)),接着使核糖部分的5-羟基磷酸化(参见Chem.Comm.,1999,729-730)而获得的。具体地,例如,首先,将烟酰胺和L-核糖四乙酸酯溶解在无水乙腈中,在氮气流中,加入过量的三甲基甲硅烷基三氟磺酸,然后在室温下搅拌,加入甲醇以停止反应,由此来制备反应溶液。将上述反应溶液倒入填充有活性炭的柱中,用蒸馏水清洗,然后用甲醇洗脱,收集其产物。接着,为了进行该产物的L-核糖部分的5-羟基的磷酸化反应,而将上述产物溶解在三甲氧基磷酸中、在冰浴条件下滴加磷酰氯,在氮气流下进行搅拌,加入氢氧化钠水溶液以中和,停止反应,由此制备反应溶液。将冷乙腈-醚溶液加入上述反应溶液中。然后,使下层(水相)通过阴离子交换树脂以收集反应物,并进一步用阳离子交换树脂进行纯化,由此可以收集到高纯度的烟酰胺单核苷酸。烟酰胺单核苷酸可购自Oriental Yeast Co.,ltd.和Bontac Bio-engineering(Shenzhen)Co.,Ltd,并且这些商业产品可被购买使用。
烟酰胺单核苷酸是含有少量杂质的纯化产物,尤其优选其纯度为90%以上,并且进一步优选其纯度为95%以上。当纯度为90%或更低时,可能产生不良气味,或者烟酰胺单核苷酸的效果可能被降低进而未能充分地提供本发明的效果。
如上所述,虽然烟酰胺单核苷酸的纯度优选为90%以上,但纯度(质量比)被定义为通过从无水项的100%中减去而获得的值。因此,烟酰胺单核苷酸的纯度可以用下式获得:烟酰胺单核苷酸纯度(%)=100-烟酰胺单核苷酸以外的杂质(%)。这里,这些杂质包括,如图1所示,在NAD代谢途径中涉及的烟酰胺单核苷酸以外的代谢物,特别是烟酰胺和烟酰胺腺嘌呤二核苷酸。当在本发明中使用的烟酰胺单核苷酸含有诸如在NAD代谢途径中涉及的上述代谢物的外来元素时,例如烟酰胺单核苷酸向生物体细胞的吸收可能降低,导致本发明的效果的降低。通过使用标准样品的绝对校准曲线方法进行NAD代谢途径中所涉及的上述杂质的定量测定,其中将干燥的烟酰胺单核苷酸粉末的测试溶液注入HPLC设备中,并且求出所获得的色谱的峰面积(纵轴:峰面积,横轴:浓度)。由于在微量物质的情况下峰高的使用确保了高精度的定量测定,因此可根据装置的特性适当地选择要使用的装置。基于保留时间识别分离的物质。
本发明的抗衰老剂易于通过单独使用烟酰胺单核苷酸或混合其他成分来制造。在提供本发明的效果的范围内,其它成分没有特别限制。
其它成分的实例包括,如上所述,已知为抑制大脑衰老的食品成分,二十二碳六烯酸(DHA)、二十碳五烯酸(EPA)、B族维生素(B6、B12、叶酸)、卵磷脂、胆碱和色氨酸;已知为增强免疫力的食品成分,维生素A、维生素E、维生素C、B族维生素(泛酸、B6、B12、叶酸)和锌;已知为增加骨量的食品成分,钙、蛋白质、维生素D和维生素K;已知为去除活性氧的食品成分,类胡萝卜素(番茄红素、叶黄素、维生素A等)、虾青素、多酚(类黄酮、儿茶素、异黄酮、芝麻素、姜黄素等)、维生素E、维生素C、辅酶Q等。还可包括常用于食品领域中的辅助成分,例如各种维生素、微量元素、柠檬酸、苹果酸、香料和无机盐作为其它成分。
在本发明中,在提高抗衰老效果方面特别有效的其他成分包括白藜芦醇。白藜芦醇已知是包含在例如葡萄皮、红酒、花生皮、日本结草和木兰中的抗氧化物质。白藜芦醇包括反式和顺式异构体、反式/顺式异构体混合物、二聚体和白藜芦醇衍生物如甲基化白藜芦醇。通常,对热稳定的反式异构体被用于健康食品等。白藜芦醇除了通过从每个原料中提取并纯化而制备之外,还可以合成制备。
白藜芦醇和烟酰胺单核苷酸的配合比例不受限制。但是,从获取本发明的最大效果的角度出发,优选调节两者的配合比例,使得在成人每天摄取量为,白藜芦醇为1-100pts.mass,烟酰胺单核苷酸为1-25pts.mass。
本发明的抗衰老剂主要通过口服,抑制衰老。在本发明中,如前所述,“抗衰老”除了在狭义上的抗衰老之外,还具有例如衰老现象的改善、衰老的延迟和回复青春等更广泛的含义,因此包括诸如使伴随年龄增长的身体功能、生理功能、心理功能的衰退得到抑制、改善、延迟、回复青春、正常化等的一切。具体地,“抗衰老”可包括针对下述问题的抑制、改善和延迟的效果,例如皮肤的衰老症状(皱纹、松垂的发生、皮肤张力的丧失等)、因衰老导致的干皮(皮肤的保湿性降低)、皮肤瑕疵、雀斑、粗糙皮肤、激素(生长激素、甲状腺激素、肾上腺皮质激素、性激素、催乳激素、抗利尿激素、甲状旁腺激素、褪黑激素等)的分泌的减少和增加、由活性氧导致的细胞(脑细胞、心肌细胞等)的损害、头发和牙齿的脱落、视力和听力的下降、运动功能的下降、骨量的降低、体力的降低、记忆力的下降、学习能力的下降、免疫功能的下降和老年病的发生等。
本发明的抗衰老剂对皮肤的衰老症状、因衰老导致的干皮(皮肤的保湿性降低)、皮肤瑕疵、雀斑、粗糙皮肤有效。在此,“皮肤的衰老症状”主要是指,例如,随着年龄增长皮肤的弹性下降导致的皱纹、松垂的发生、皮肤张力的损失等。关于本发明抑制和改善皮肤衰老症状的原因,可以想到,烟酰胺单核苷酸激活衰退的皮肤代谢功能,促进胶原形成,并且另外,如稍后将描述的,减少活性氧。
本发明的抗衰老剂可用于通过向面部、手部等的皮肤提供水分来持续改善皮肤的保湿性,进而改善干皮。通过本发明的应用,增加了皮肤中水分的量并改善了皮肤的保湿性能,其结果是例如皮肤干燥、张力、弹性和柔性等得到改善。关于通过本发明能改善皮肤保湿性的原因,可以想到,例如烟酰胺单核苷酸对天然保湿因子和角质细胞间脂质的影响,促进透明质酸的形成等。
本发明的抗衰老剂可用于获得抑制黑色素随年龄增长而形成和沉积,并抑制或改善皮肤瑕疵和雀斑的美白效果。关于本发明提供美白效果的原因,可以想到,例如烟酰胺单核苷酸促进黑色素的排出等。
本发明的抗衰老剂可用于抑制和改善随年龄增长而粗糙的皮肤。根据粗糙皮肤的原因,适当地配合例如抗炎剂、维生素、激素、植物提取物、杀菌剂和油性成分等更有效。关于通过本发明具有抑制和改善粗糙皮肤效果的原因,可以想到,例如烟酰胺单核苷酸改善了长寿蛋白在皮肤组织中的活性。
此外,本发明的抗衰老剂改善了一种或两种以上的选自几种激素(其分泌量主要与年龄成比例地减少的激素)的分泌,具体地例如生长激素、甲状腺激素、肾上腺皮质激素、性激素,催乳激素、抗利尿激素、甲状旁腺激素和褪黑激素,使由这些激素中的每一种提供的生理效果回复青春,由此发挥抗衰老效果。因此,本发明的抗衰老剂可以用作改善这些激素分泌的用途。此外,“激素分泌的改善”是指促进或抑制激素分泌量从而向合理的方向引导激素分泌量。
生长激素是主要在下丘脑中的垂体附近分泌的激素。生长激素被分泌到目标器官中以促进该器官组织的生长,并用于控制代谢。生长激素,也称为“回复青春激素”,随着年龄增长基础分泌的和反应性下降。认为这种下降的机制包括,例如,生长激素分泌细胞的减少、产量的降低、对生长激素释放激素的反应性的下降、对生长激素分泌细胞的胰岛素样生长因子(IGF-1)的敏感性增加、下丘脑中生长激素释放激素的分泌不足,生长激素抑制素的分泌过多。在成人的情况下,生长激素据说在维持健康人群感到健康的正常感觉方面发挥重要作用。此外,生长激素据说具有例如增强记忆力、抑制疲劳感和情绪下降、改善骨密度、保持生殖功能、增强免疫功能、加速脂肪燃烧和促进肌肉生长等的效果。
甲状腺激素是由甲状腺分泌的激素,其中已知两种类型的甲状腺素(T4)和三碘甲状腺原氨酸(T3),通常作用于全身的细胞以增加细胞的代谢率。已知甲状腺自身的功能随着年龄增长而降低,并且甲状腺刺激激素(TSH)对甲状腺激素释放激素(TRH)的反应性降低,从而减少了三碘甲状腺原氨酸的分泌量。具体地,甲状腺激素据说具有例如,增强皮肤保湿性、增强记忆力、抑制疲劳和情绪下降、抑制中年发福、抑制对感冒敏感和抑制头发变稀。
肾上腺皮质激素是肾上腺皮质分泌的激素。肾上腺皮质被分成球状带、束状带和网状带。由球状带产生盐皮质激素,由束状带产生糖皮质激素,而网状带产生肾上腺性激素。肾上腺皮质激素具有许多生理作用,例如:抗炎作用、免疫抑制作用、抗压作用、水-电解质调节作用、碳水化合物代谢作用、脂类代谢作用、合成代谢作用、合成代谢抑制作用、血凝加速作用和垂体抑制作用等。此外,雄激素是男性激素的总称。与由睾丸分泌的睾酮相比,作为肾上腺雄激素的男性激素的生物活性较弱。
性激素广泛地分为主要产生于睾丸间质细胞的男性激素和从卵巢分泌的女性激素。男性激素用于增强所谓的男性特征,其在20-30岁时达到峰值,并且此后分泌逐渐降低。典型的男性激素是睾酮。男性激素具有例如维持骨和肌肉的力量、维持性功能、维持血管状态、抑制动脉硬化以及抑制代谢综合征等的功能。另一方面,存在两种类型的女性激素:产生女性气质的卵泡激素(雌激素)和有助于妊娠的黄体激素(黄体酮)。女性在50岁左右进入更年期;女性激素的分泌急剧降低,并且出现骨质疏松症和作为所谓的自律神经失调症的症状(例如,潮热、出汗、倦怠感和头晕等)。
催乳激素是主要由垂体前叶分泌的激素,具有促进乳腺发育、促进乳汁的产生和分泌、性腺抑制作用、黄体功能维持、子宫内膜增生、水-电解质调节作用和免疫刺激作用。据说由于雌激素的减少,女性的催乳激素浓度从绝经前后降低。
抗利尿激素是由垂体后叶分泌的激素,并作用于肾脏的肾小管以浓缩尿液并水分保留在体内。当肾脏的功能随着年龄增加而衰退时,浓缩尿液的功能降低,释放了大量的稀尿,使得水分难以保持在体内;抗利尿激素具有抑制这种情况的功能。年纪越大抗利尿激素分泌量越少,其结果是尿频、尿漏和夜间排尿。
甲状旁腺激素是由甲状旁腺分泌的激素,并且具有与从甲状腺分泌的降钙素和维生素D一起保持血液和体液中的钙浓度的功能。也就是说,随着年龄增加,钙吸收降低,导致甲状旁腺激素的连续过量分泌,并且这种过量的分泌导致破骨细胞破坏旧骨的骨吸收和骨转换的增多,导致作为老年病之一的骨质疏松症。
褪黑激素是由大脑的松果体分泌的激素,也被称为“睡眠激素”。褪黑激素涉及生物的生物节律,影响人的睡眠和觉醒,在夜间,具有舒缓神经的作用,使人直接进入睡眠。在夜间,分泌较高,并且观察到在醒来时停止分泌的昼夜变化。褪黑激素在儿童期分泌最多,随年龄增长褪黑激素的分泌量降低,在60岁以后褪黑激素在夜间的增加几乎可以忽略。随着年龄增加而褪黑激素分泌量减少导致睡眠时间变短,导致睡眠障碍;老年人通常患有睡眠障碍。由于褪黑激素除了诱导睡眠之外,还能通过抗氧化作用促进细胞的代谢并缓解疲劳,因此据说能发挥抗衰老作用,是受到注目的激素之一。进一步的,褪黑激素作用于如神经递质、激素和细胞因子等各种生理活性物质的功能,发挥其作为控制神经系统和免疫系统的生物反应调节剂的作用,调节许多生物功能,这种调节在抗衰老的方向上起作用。
本发明的抗衰老剂减少被称为衰老的原因之一的活性氧(超氧化物、过氧化氢、羟基自由基),以保护细胞免受活性氧的影响,从而有助于抗衰老。因此,出于减少活性氧的目的,可以使用本发明的抗衰老剂。特别地,在生物体中,当皮肤暴露于紫外线时,在皮肤中容易产生活性氧。因此,可以想到,活性氧的减少是如上所述在皮肤中具有抗衰老效果的原因之一。尽管在本发明的抗衰老剂中,活性氧降低的机理仍在研究中,但可以想到,抗衰老剂通过活化例如Sirt1来增强细胞内的抗氧化功能从而发挥其作用。
用于制造抗衰老剂的方法没有特别限制,可以与其形态对应地适当选择用于制造抗衰老剂的一般制造方法。例如,当形态为粉末时,可通过均匀混合烟酰胺单核苷酸和根据需要而包含的其它成分来制造抗衰老剂。作为活性成分的烟酰胺单核苷酸在市场上流通并且是可商购的。特别地,对于烟酰胺单核苷酸,最近已经建立了烟酰胺单核苷酸的质量管理体系和量产体系。
本发明的抗衰老剂可用作食品和医疗产品。在用作食品的情况下,抗衰老剂在食品领域可以作为抗衰老用食品而提供。食品形态的日常摄取持续提供抗衰老效果,在抗衰老方面特别有效。作为本发明的对象的食品的类型没有特别限制,除了一般食物产品之外,还可以包括功能性食品、特定保健用食品、膳食补充食品、食物添加剂、饲料、护理食品、饮食治疗食品、治疗饮食、减肥食品和类似食品。具体地,例如,甜食(口香糖、糖果、甜饼、橡皮糖、饼干、蛋糕、巧克力、日本糖果、果冻等)、面包、面条、大米/谷物加工食品(谷类等)、肉类加工食品、鱼和贝类加工食品、蔬菜加工食品、现成食品、发酵食品、调味品(酱,调料、番茄酱等)、香料、乳制品(酸奶、奶酪、牛奶等)、冰淇淋、冷冻食品、蒸煮袋食品、饮料(碳酸饮料、软饮料、乳类饮料、酒精饮料、运动饮料、果味饮料、茶、营养饮料、浓缩饮料等)、粉末状饮料(粉末汁,粉末汤等)。食品的形态不受限制,尤其是在功能性食品物、特定保健用食品等的情况下,食品可以加工成例如粉末、片剂、丸剂、颗粒、硬胶囊制剂、软胶囊制剂、果冻、液剂和膏剂等形态而提供。
食品的摄取根据食品的类型、摄取食品的对象的年龄、性别和体重、预期效果和症状等而不同。然而,包含在食品中的烟酰胺单核苷酸的每日摄取量通常为1mg-500mg,优选为5mg-300mg,更优选为50mg-300mg。少于1mg,则恐不能实现本发明的效果,而多于500mg则仅提供几乎相似的效果却在经济上不利。食品中烟酰胺单核苷酸的配合比例可以相对于总食物重量在100%以下的范围内适当地设定。
上述食品安全且未特别发现有副作用。因此,为了抗衰老的目的,可以长时间摄取上述食品。不仅可以适用于老年人,还可以适用于年轻人。
同时,本发明的抗衰老剂在医药领域可以作为抗衰老用的药品(包括准药品,quasi-drugs)口服或非口服给药。所述药品的剂型没有特别限制,可包括,例如,粉末、片剂、持续性片剂、咀嚼片、泡腾片、含片(troche)、口含片(buccal tablet)、舌下片、胶囊剂、细颗粒剂、颗粒剂、丸剂、干糖浆、液剂、悬浮剂、糖浆、如酏剂等的口服给药的制剂,滴眼剂、洗眼液、眼药膏、注射剂、输液、外用制剂。在这些剂型中,考虑到服用方便、活性成分的稳定性等,优选如粉末、片剂和胶囊剂等口服给药的制剂。
考虑到物理化学性质、生物学性质等类似的性质,上述药品可适当地含有适合于其剂型的药理上允许的已知的制剂用添加剂。作为这种制剂用添加剂可列举为例如赋形剂(乳糖、淀粉、结晶纤维素、磷酸钠等)、溶剂(水、大豆油、盐水、注射用非水性溶剂等)、粘合剂(淀粉、明胶、阿拉伯树胶、海藻酸钠、羧甲基纤维素钠、甲基纤维素、乙基纤维素、羟丙基甲基纤维素、羟丙基纤维素、聚乙烯吡咯烷酮等)、崩解剂(淀粉、羧甲基纤维素钠等)、润滑剂(滑石、硬脂酸镁、硬脂酸钙、聚乙二醇、蔗糖脂肪酸酯等)、包衣剂(白糖、HPC、虫胶、明胶、甘油、羟丙基甲基纤维素,羟丙基甲基纤维素邻苯二甲酸酯、醋酸纤维素邻苯二甲酸酯等)、稳定剂(亚硫酸氢钠、硫代硫酸钠、乙二胺四乙酸钠、柠檬酸钠、抗坏血酸、二丁基羟基甲苯等)、防腐剂(对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯、苄醇、苯酚、氯丁醇,苯扎氯铵、苄索氯铵、脱氢乙酸钠、硫柳汞等)、粘稠剂(甲基纤维素、羧甲基纤维素钠、硫酸软骨素、海藻酸钠等)、悬浮剂(各种非离子表面活性剂、甲基纤维素、羧甲基纤维素钠等)、乳化剂(阿拉伯树胶、胆固醇、脱水山梨醇倍半油酸酯,聚山梨酯80、月桂基硫酸钠等)、缓冲剂(柠檬酸、乙酸、磷酸钠和硼酸)、表面活性剂(氢化蓖麻油、聚山梨酯80等)、着色剂(水溶性食用色素、色淀色素等)、矫味剂(乳糖、白糖、葡萄糖、甘露醇等)、芳香剂(芳族精油),增塑剂(邻苯二甲酸酯、植物油、聚乙二醇等)。
上述药品的剂量根据例如给药对象的年龄、体重、症状、给药次数等而不同,因此不能被同等地限定。但是,作为该药品的剂量,成人每天烟酰胺单核苷酸的给药量通常为1mg-500mg,优选为5mg-300mg,更优选为50mg-300mg。少于1mg,则恐不能实现本发明的效果,而多于500mg则仅提供几乎相似的效果却在经济上不利。药品中烟酰胺单核苷酸的配合比例可以根据剂型、药品的剂量等进行适当设定。
上述药品的给药次数可以根据例如给药对象的年龄、体重、症状和每次给药的剂量适当地设定。每天给药的次数可以举例说明为1-3次。
由于烟酰胺单核苷酸具有如上所述的抗衰老效果,因此本发明还提供了抗衰老方法,使需要有效剂量的烟酰胺单核苷酸的对象摄取有效剂量的烟酰胺单核苷酸。即,一种用于通过使对象摄取本发明的抗衰老剂而抑制进行摄取的对象进的衰老的方法。进行摄取的对象优选为哺乳动物,例如人、小鼠、大鼠、兔、狗、猫、牛、马、猪和猴等,特别优选为人。在该方法中,烟酰胺单核苷酸的摄取量、每天的摄取次数以及类似的事项如针对抗衰老剂所述。抗衰老剂可在任何情况任何时间下摄取,且可长时间被对象摄取。
[实施例]
下文基于实施例对本发明进行详细说明,而本发明不受这些实施例的限制。
[实施例]
1.烟酰胺单核苷酸对褪黑激素分泌促进效果的评价
为了证实在摄取烟酰胺单核苷酸之前和之后褪黑激素的变化,对年龄为50至70岁的健康男性和女性进行了测试。
作为实施例1的样品,使用含有烟酰胺单核苷酸和淀粉(4个胶囊的烟酰胺单核苷酸为100mg(低剂量)和200mg(高剂量)(新兴和制药株式会社制造)的胶囊制剂。
在无偏见年龄组中由50岁至70岁的五个健康男性和五个健康女性年龄构成的每组,一天一次摄取低剂量的上述胶囊制剂,持续24周(总共10个受试者,低剂量组:100mg/日摄取)。另一方面,在无偏见年龄组中由50岁至70岁的五个健康男性和五个健康女性年龄构成的每组,一天一次摄取高剂量的上述胶囊制剂,持续24周(总共10个受试者,高剂量组:200mg/日摄取)。为了进行适当的评价,将长期使用用于慢性疾病的药品的人、已经使用有可能影响临床研究的健康食品的人和当前正在参加其它临床研究或临床试验的人或者已经在最近三个月内参加过与其它临床研究或临床试验的人被排除在受试者之外。将胶囊制剂与水或温水(口服给药)一起在10am(在餐食和空腹状态之间)摄取。
血浆中的褪黑激素的定量测定请求外部公共组织依据通常的方法进行。图2a至图2c表示血液褪黑激素浓度(pg/mL)在24周中的转变。图2a表示全部受试者的转变;图2b表示男性受试者的转变;图2C表示女性受试者的转变。图3a至图3c表示,当烟酰胺单核苷酸被口服施用给受试者24周时,血液褪黑激素浓度至24周时的变化率(%)。图3a表示全部受试者的变化率;图3b表示男性受试者的变化率;图3c表示女性受试者的变化率。进一步的,表1表示在摄取烟酰胺单核苷酸之前(0周)和摄取烟酰胺单核苷酸之后(24周)血液褪黑激素浓度(pg/ml)的数值。此外,数值表示平均值±标准偏差。
表1
2.评价结果
从如图2a至图2c和图3a至图3c所示的结果可以看出,烟酰胺单核苷酸的摄取以高变化率增加了血液褪黑激素浓度。此外,如表1所示,作为整体,与摄取前相比,血液褪黑素浓度在低剂量组和高剂量组均观察到显著差异(p<0.05)。
从上述结果中,可以确认通过对中老年男性和女性口服施用烟酰胺单核苷酸能达到促进褪黑激素分泌的效果,并且明确烟酰胺单核苷酸对抗衰老是有效的。
此外,上述评价的受试者摄取24周之后未显示任何未识别的病症,例如腹痛、恶心、呕吐、头痛或排便异常,可确认烟酰胺单核苷酸的安全性。
Claims (8)
1.一种抗衰老剂,含有烟酰胺单核苷酸作为活性成分。
2.根据权利要求1所述的抗衰老剂,其中,
所述抗衰老剂用于改善皮肤的衰老症状、干皮、皮肤瑕疵、雀斑或粗糙皮肤。
3.根据权利要求1所述的抗衰老剂,其中,
所述抗衰老剂用于改善激素分泌。
4.根据权利要求3所述的抗衰老剂,其中,
所述激素是选自生长激素、甲状腺激素、肾上腺皮质激素、性激素、催乳激素、抗利尿激素、甲状旁腺激素和褪黑激素中的一种或两种以上。
5.根据权利要求1所述的抗衰老剂,其中,
所述抗衰老剂用于降低活体内的活性氧。
6.根据权利要求1-5中任一项所述的抗衰老剂,其中,
所述抗衰老剂是用于抗衰老的食品。
7.根据权利要求1-5中任一项所述的抗衰老剂,其中,
所述抗衰老剂是用于抗衰老的药品。
8.一种抗衰老方法,所述方法包括使受试者摄取有效剂量的烟酰胺单核苷酸,所述受试者需要有效剂量的烟酰胺单核苷酸(排除对人的医学治疗)。
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CN113100439A (zh) * | 2021-05-17 | 2021-07-13 | 时代特殊医学用途配方食品(深圳)有限公司 | 一种延长染色体端粒的nmn配方产品及其制备方法 |
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WO2019054485A1 (ja) | 2019-03-21 |
JPWO2019054485A1 (ja) | 2020-10-15 |
KR20200053580A (ko) | 2020-05-18 |
JP7210459B2 (ja) | 2023-01-23 |
US11219590B2 (en) | 2022-01-11 |
EP3682746A4 (en) | 2021-03-10 |
US20200268632A1 (en) | 2020-08-27 |
EP3682746A1 (en) | 2020-07-22 |
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