CN103037854A - 潘多汀派生物或提琴形凹唇姜萃取物的促进增加肌肉、抗疲劳及提高运动执行能力相关新用途 - Google Patents
潘多汀派生物或提琴形凹唇姜萃取物的促进增加肌肉、抗疲劳及提高运动执行能力相关新用途 Download PDFInfo
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Abstract
本发明涉及潘多汀(panduratin)派生物或提琴形凹唇姜萃取物的促进增加肌肉、抗疲劳及提高运动执行能力相关新用途,尤其涉及以有效成分含有潘多汀派生物或其盐或提琴形凹唇姜萃取物,促进增加肌肉及疲劳恢复,提高引动性的可提高运动执行能力,促进增加肌肉及抗疲劳的合成物;把潘多汀派生物或其盐或提琴形凹唇姜萃取物投入到需要其的个体,以此提高运动执行能力,促进增加肌肉及抗疲劳的方法。本发明的潘多汀派生物或提琴形凹唇姜萃取物无副作用,使用安全,通过提高肌肉内PPARδ的激活量,可以增加肌肉量、恢复疲劳、提高运动能力,其效果非常优秀。
Description
技术领域
本发明以于2010年5月20日申请的大韩民国专利申请第10-2010-0047369号主张优先权,该说明书所有部分是本发明的参考文献。
本发明涉及潘多汀派生物或提琴形凹唇姜萃取物的促进增加肌肉、抗疲劳及提高运动执行能力相关新用途,尤其涉及以有效成分含有潘多汀派生物或其盐或提琴形凹唇姜萃取物,促进增加肌肉及疲劳恢复,提高引动性的可提高运动执行能力,促进增加肌肉及抗疲劳的合成物;把潘多汀派生物或其盐或提琴形凹唇姜萃取物投入到需要其的个体,以此提高运动执行能力,促进增加肌肉及抗疲劳的方法。
背景技术
通常,肌肉如不持续运动,则因老化肌肉功能会降低、肌肉量及神经肌肉接头(neuromuscular junction,motor unit)会减少、让人容易感到疲劳、无精打采、降低生活活力、导致生活质量急剧降低(J.Appl.Physiol.2003,95,1717-1727)。为了防止这一问题,人们通常持续实施如阻力训练(resistance training)等运动(大韩民国公开专利10-2009-0089815),并辅以适当的饮食疗法。为了提高生活质量,需要进行有规则的健康运动。因此,不仅是运动员,连普通人都需要用更多的精力做更多的运动,提高身体活力。但是对于繁忙的现代人来说,与其做运动,大部分人更加依赖于健康补充剂(dietary supplement)。因此,长久以来大量进行着有关可提高运动之星能力的辅助剂、功能食品、食品合成物等的研究。研究表明,服用类固醇(steroid)、咖啡因(caffeine)可以提高运动能力。但这些药物伴随着致命的副作用,其使用存在很大的限制。
骨骼肌纤维(skeletal muscle fibre)通常被分为I型(Oxidative/slow)和II型(glycolytic/fast)纤维。肌纤维按其形态,在收缩、代谢、疲劳感(susceptibility tofatigue)方面,表现出巨大差异。I型纤维含丰富的线粒体(mitochondria),其生成能量主要靠氧化代谢(Oxidative metabolism),可以长期稳定地供应ATP,可以抗疲劳。从而,I型纤维多的骨骼肌不会出现大量肌肉消耗(Muscle Nerve 2005,31,p339-348)。II型纤维的线粒体和氧化酶含量少,其主要靠糖酵解代谢(glycolytic metabolism)产生能量,易于疲劳。
PPARδ(过氧化物酶体增殖物激活受体扩散者δ(Peroxisome ProliferatorActivated Receptor δ))主要存在于骨骼肌,特别是多见于I型纤维(PPAPα的10被PPARγ的50倍),激活长链脂肪酸的β氧化相关的酶、燃烧脂肪细胞内脂肪的主要转录调节因子(transcriptional regulatory factor)(Cell 2003,113,p159-170),是促进I型纤维形成的第1转录因子(transcription factor)。据研究,这种PPARδ被激活后,参与有关调节线粒体的生物合成(biosynthesis)、提高运动能力、提高抵抗肥胖机能的一系列复杂生物反应(PLOS Biology 2004,2,p1532-1539)。从而通过运动、以适应运动的原理生成的I型纤维,其抗疲劳能力非常强。据研究,在不运动的情况下,在肌肉内人为地激活过多的PPARδ也能带来同等效果。在老鼠的肌肉中人为激活过多PPARδ的结果,线粒体的生物合成增加,并增加了脂肪酸β氧化酶的激活及I型纤维,使实验鼠的持久跑动的时间和距离与普通鼠相比分别增加了67%、92%(PLOS Biology 2004,2,p1532-1539)。可以看出,PPARδ激活时,可以改变肌肉纤维的形态,可以带来运动执行能力提高的结果。
发明内容
技术课题
本发明的各发明人员探索既能提高肌肉内PPARδ活性,又安全的天然物。通过研究发现姜科(Zingiberaceae family)植物提琴形凹唇姜(Boesenbergia pandurata)的萃取物及从其分离出的潘多汀(panduratin)派生物具有提高肌肉内PPARδ蛋白的激活,促进肌肉增强及疲劳恢复,提高运动执行能力的功效,完成了本发明。
本发明是鉴于如上所述现有技术的问题而提出的,其目的在于提供一种以有效成分含有潘多汀派生物或其盐的提高运动执行能力用合成物。
本发明的另一目的在于提供一种以有效成分含有提琴形凹唇姜(Boesenbergiapandurata)萃取物的提高运动执行能力用合成物。
本发明的另一目的在于提供一种以有效成分含有潘多汀派生物或其盐的肌肉增加促进用合成物。
本发明的另一目的在于提供一种以有效成分含有提琴形凹唇姜萃取物的肌肉增加促进用合成物。
本发明的另一目的在于提供一种以有效成分含有潘多汀派生物或其盐的抗疲劳用合成物。
本发明的另一目的在于提供一种以有效成分含有提琴形凹唇姜萃取物的抗疲劳用合成物。
本发明的另一目的在于提供一种把潘多汀派生物或其盐以有效量投入到需要其的个体为特征的运动执行能力提高方法。
本发明的另一目的在于提供一种用于制造运动执行能力提高用制剂的潘多汀派生物或其盐的用途。
本发明的另一目的在于提供一种把提琴形凹唇姜萃取物以有效量投入到需要其的个体为特征的运动执行能力提高方法。
本发明的另一目的在于提供一种用于制造运动执行能力提高用制剂的提琴形凹唇姜萃取物的用途。
本发明的另一目的在于提供一种把潘多汀派生物或其盐以有效量投入到需要其的个体为特征的增加肌肉促进方法。
本发明的另一目的在于提供一种用于制造增加肌肉促进用制剂的潘多汀派生物或其盐的用途。
本发明的另一目的在于提供一种把提琴形凹唇姜萃取物以有效量投入到需要其的个体为特征的增加肌肉促进方法。
本发明的另一目的在于提供一种用于制造增加肌肉促进用制剂的提琴形凹唇姜萃取物的用途。
本发明的另一目的在于提供一种把潘多汀派生物或其盐以有效量投入到需要其的个体为特征的抗疲劳方法。
本发明的另一目的在于提供一种用于制造抗疲劳用制剂的潘多汀派生物或其盐的用途。
本发明的另一目的在于提供一种把提琴形凹唇姜萃取物以有效量投入到需要其的个体为特征的抗疲劳方法。
本发明的另一目的在于提供一种用于制造抗疲劳用制剂的提琴形凹唇姜萃取物的用途。
技术方案
为了达到如上所述的目的,本发明的提高运动执行能力用合成物以有效成分含有潘多汀派生物或其盐的。
为了达到如上所述的目的,本发明的提高运动执行能力用合成物以有效成分含有提琴形凹唇姜萃取物。
为了达到如上所述的目的,本发明的肌肉增加促进用合成物以有效成分含有潘多汀派生物或其盐。
为了达到如上所述的目的,本发明的肌肉增加促进用合成物以有效成分含有提琴形凹唇姜萃取物。
为了达到如上所述的目的,本发明的抗疲劳用合成物以有效成分含有潘多汀派生物或其盐。
为了达到如上所述的目的,本发明的抗疲劳用合成物以有效成分含有提琴形凹唇姜萃取物。
为了达到如上所述的目的,本发明的运动执行能力提高方法把潘多汀派生物或其盐以有效量投入到需要其的个体。
为了达到如上所述的目的,本发明提供一种用于制造运动执行能力提高用制剂的潘多汀派生物或其盐的用途。
为了达到如上所述的目的,本发明的运动执行能力提高方法把提琴形凹唇姜萃取物以有效量投入到需要其的个体。
为了达到如上所述的目的,本发明提供一种用于制造运动执行能力提高用制剂的提琴形凹唇姜萃取物的用途。
为了达到如上所述的目的,本发明的增加肌肉促进方法把潘多汀派生物或其盐以有效量投入到需要其的个体。
为了达到如上所述的目的,本发明提供一种用于制造增加肌肉促进用制剂的潘多汀派生物或其盐的用途。
为了达到如上所述的目的,本发明的增加肌肉促进方法把提琴形凹唇姜萃取物以有效量投入到需要其的个体。
为了达到如上所述的目的,本发明提供一种用于制造增加肌肉促进用制剂的提琴形凹唇姜萃取物的用途。
为了达到如上所述的目的,本发明的抗疲劳方法把潘多汀派生物或其盐以有效量投入到需要其的个体。
为了达到如上所述的目的,本发明提供一种用于制造抗疲劳用制剂的潘多汀派生物或其盐的用途。
为了达到如上所述的目的,本发明的抗疲劳方法把提琴形凹唇姜萃取物以有效量投入到需要其的个体。
为了达到如上所述的目的,本发明提供一种用于制造抗疲劳用制剂的提琴形凹唇姜萃取物的用途。
下面,对本发明进行详细说明。
本发明的合成物作为有效成分含有潘多汀派生物或其盐,该物质增加肌肉细胞的PPARδ激活量、增加肌肉量,恢复疲劳、提高运动执行能力。
潘多汀派生物是包括如下化学式1的潘多汀A(panduratin A),化学式2的4-羟基潘多汀A(4-hydroxy panduratin A)及化学式3的ISO潘多汀A(i sopanduratin A)的物质。潘多汀A是(2,6-二羟基-4-甲氧基苯基)[3-甲基-2-(3-甲基丁-2-烯基)-5-苯基环己胺-3-烯基]甲酮
所述潘多汀派生物是可通常购买的物质,或可通过公知的合成方法制造的物质,可从提琴形凹唇姜萃取物或挤压提琴形凹唇姜植物所得油分离、提纯获得。
【化学式1】
【化学式2】
【化学式3】
包含在本发明合成物的潘多汀派生物可以通过适合于食品加工的纯净水、乙醇及亚临界水或超临界水二氧化碳,从提琴形凹唇姜根茎(rhizome)萃取、提纯获得,或者挤压提琴形凹唇姜植物获得植物油后,从该植物油分离、提纯获得。为了获得本发明合成物含有的潘多汀或其盐或提琴形凹唇姜萃取物可使用的溶媒,除了所述萃取溶媒外,还有甲醇(methanol)、丙醇(propanol)、异丙醇(iso propanol)、丁醇(butanol)、丙酮(acetone)、乙醚(ether)、苯(benzene)、三氯甲烷(Chloroform)、乙酸乙酯(Ethyl acetate)、二氯甲烷(Methylene chloride)、己烷(Hexane)、环己烷(cyclohexane)、石油醚(Petroleumether)等。这些溶媒可以单独或混合使用。
从提琴形凹唇姜萃取物分离及提纯潘多汀派生物时,可以单独或并用填充有硅胶(silica gel)或氧化铝(alumina)等各种合成树脂的柱层析(Column Chromatography)仪及高效液相色谱(high-performance liquid chromatography:HPLC)仪等。但潘多汀派生物的萃取及分离提纯方法并不只限于该方法。
本发明的合成物,其特征在于具有提高运动执行能力的效果。“运动执行能力”与运动员的竞技状态、比赛记录有密切关系,通过加强心肺功能、促进能量代谢、加快疲劳恢复及提高肌肉力量,提高竞技状态及比赛记录。即,快速恢复由于长期训练所积累的疲劳,提高运动时的耐力,可以提高运动执行能力。本发明的合成物提高大量存在于骨骼肌纤维I型纤维的PPARδ的激活量。如前所述,PPARδ是促进I型纤维转录的因子,I型纤维多的肌肉主要以脂肪为能量源,不会产生乳酸,肌肉内不会积累疲劳,可以提高运动执行能力。
本发明涉及以有效成分含有提琴形凹唇姜(Boesenbergia pandurata)萃取物的合成物。提琴形凹唇姜是姜科(Zingiberaceae family)植物,也叫作凹唇姜(Kaempferiapandurata)。提琴形凹唇姜萃取物含有生松素查尔酮(pinocembrin chalcone)、豆蔻明(cardamonin)、生松素(pinocembrin)、pinostribin、4-羟基潘多汀A(4-hydroxypaduratin A)、PANDURATI A及异潘多汀A(iso潘多汀A)等成分。据报告,所述成分具有抗癌效果(Trakoontivakorn,G.,等,J.Arig.Food Chem.,49,30463050,2001;Yun,J.M.,等,Carcinogenesis,27(7),14541464,2006)、抗炎效果(Yun,J.M.,等,Planta Medica,69,11021108,2003)、抗皮肤老化作用(Shim,J.S.,等,PlantaMedica,74,239244,2008)或抗菌效果(Hwang,J.K.,等,Int.J.Antimicrob.Agents,23,377381,2004;Park,K.M.,等,Food Sci.Biotechnol.,14(2),286289,2005),但本发明之前不曾提出其促进肌肉增强及疲劳恢复,提高运动能力的效果。
本发明的一实施例中,从提琴形凹唇姜萃取物萃取、分离了潘多汀A。(参考实施例1至2)
本发明的另一实施例中,使用了通过饮食高度肥胖的实验鼠,让实验鼠分别摄取已分离的潘多汀及提琴形凹唇姜萃取物。其结果表明肌肉细胞的PPARδ激活量,肌肉量及运动能力得到了提高。(参考实施例3至5)
本发明的潘多汀派生物,可以以其本身或其盐或医药学方面允许的盐的形式使用。所述‘医药学方面允许的’是指从生理学角度获得许可,人类摄取时不会引起过敏反应或与之类似的反应。所述盐是利用药剂学上可使用的游离酸(free acid)形成的酸式盐(acidsalt)为宜。所述游离酸可以使用有机酸和无机酸。所述有机酸包括但不局限于(citricacid)、醋酸(acetic acid)、乳酸(lactic acid)、酒石酸(tartaric acid)、马来酸(maleicacid)、富马酸(fumaric acid)、甲酸(formic acid)、丙酸(propionic acid)、草酸(oxalicacid)、三氟乙酸(tri-fluoroacetic acid)、安息香酸(benzoic acid)、葡萄糖酸(gluconicacid)、甲基磺酸(metha sulfonic acid)、乙醇酸(glycollic acid)、丁二酸(succinicacid)、4-甲苯磺酸(4-toluene sulfonic acid)、谷氨基酸(glutamic acid)、天冬氨酸(aspartic acid)。所述无机酸包括但不限于盐酸、溴酸(bromic acid)、硫酸、磷酸。
本发明的合成物的特征在于具有促进肌肉增加效果。“肌肉增加”是指在身体成分中特别提高肌肉性能的情况,通过身体运动及提高耐力,增加肌肉量,也可以通过向体内投入具肌肉增加效果的物质,增加肌肉量。肌肉的种类没有限制,但本发明的合成物具有促进增加特别是I型骨骼肌纤维的效果。
本发明的合成物,其特征在于具有抗疲劳效果。“疲劳”可分为精神上的疲劳和肉体上的疲劳。本发明中“疲劳”是指执行运动后肌肉中累积的肉体上的疲劳,其诱发与肌肉内的糖原(glycogen)浓度、乳酸脱氢酶(lactic dehydrogenase)的活性及柠檬酸的合成酶活性有关。本发明的合成物通过增加对I型骨骼肌纤维的转录有促进作用的PPARδ激活量,让I型骨骼肌纤维通过氧化代谢充分合成ATP,让肌肉的疲劳积累程度降低。
本发明的合成物可以以药学合成物或食品合成物的形态提供。本发明的药学合成物以有效量单独含有潘多汀派生物或提琴形凹唇姜萃取物,或者在药学允许的范围内含有一种以上载体(carrier)。本发明的药学合成物可以含有0.01至99.99%潘多汀派生物或提琴形凹唇姜萃取物,其余百分比可由在药学上允许的载体占据。
本发明的潘多汀派生物或提琴形凹唇姜萃取物在药学上的有效量为0.001至300mg/day/体重kg,最好是0.01至200mg/day/体重kg。但药学上的有效量按疾病、病情、患者年龄、体重、健康状态、性别、投入途径、治疗期间等各种因子,可适当变化。
上面说的“药学上允许的”是指从生理学角度可以使用,并在投入到人身后不会阻碍活性成分的作用,不引起胃脏障碍、眩晕等过敏反应或与之类似反应的非毒性合成物。所述载体包括一切种类的溶媒、分散介质(dispersive medium)、水包油(oil-in-water)或油包水(water-in-oil)乳液(emulsion)、水溶性合成物、微脂粒(liposome)、微珠(micro bead)、微粒体(Microsomal)。
另外,本发明的药学合成物,可根据投入路径,与适合的载体一起制造成制剂型。本发明的药学投入路径包括但不限于经口及非经口投入。非经口投入比如包括经皮肤、鼻腔、腹腔、肌肉、皮下、经脉等各种路径。
如果经口投入本发明的药学合成物时,本发明的合成物与适当的经口投入用载体一起,按本行业公知的方法,可制造成粉末、颗粒(granule)、片剂(tablet)、丸剂、糖衣片剂、胶囊(capsule)、液剂、凝胶、糖浆剂、悬浊液、圆片(wafer)等形态。适合的载体包括乳糖(lactose)、右旋糖(dextrose)、蔗糖(sucrose)、山梨醇(sorbitol)、甘露醇(mannitol)、木糖醇(xylitol)、赤藓糖醇(Erythritol)、麦芽糖醇(maltitol)等糖类,玉米淀粉、大麦淀粉、大米淀粉、土豆淀粉等淀粉类,纤维素(cellulose)、甲基纤维素(methyl cellulose)、羧甲基纤维素钠(sodium carboxymethyl cellulose)、羟丙甲纤维素(Hydroxypropyl methyl Cellulose)等纤维素(Cellulose)类,明胶(gelatin)、聚乙烯吡咯烷酮(polyvinyl pyrrolidone)等填充剂。有时,可根据情况,作为崩解剂(disintegrating agent)可以添加交联键聚乙烯吡咯烷酮(cross-linked bondpolyvinylpyrrolidone)、琼脂(agar)、藻酸(alginic acid)或海藻酸钠(sodium alginate)。所述药学合成物还可以包括抗凝聚剂(cohesive agents)、润滑剂、湿润剂、香料、油化剂、防腐剂等。
如果以非经口途径投入本发明的药学合成物,则其可与适当的非经口用载体一起,按本行业公知的方法,制造成注射剂、鼻腔吸入剂等制剂。如果制造成注射剂,则必须杀菌,要避免被细菌及真菌等微生物污染。作为注射剂的适当载体包括但不限于水、乙醇(ethanol)、多元醇(polyol:比如丙三醇(glycerol)、丙二醇(propylene glycol)、液态聚乙二醇(polyethylene glycol)等),这些物质的混合物及/或包括植物油的溶媒会分散介质。最好是,作为适当的载体,可以使用汉克斯(Hanks)溶液、吊瓶(Ringer)输液溶液、含三羟乙基胺(triethanolamine)的磷酸盐缓冲盐水(PBS(phosphate bufferedsaline))或注射用杀菌水、10%乙醇、40%丙二醇及5%葡萄糖(dextrose)等等张溶液(isotonic solution)。
为了防止所述注射剂受到微生物的污染,可以外加包括尼泊金(paraben)、氯丁醇(Chlorobutanol)、苯酚(phenol)、山梨酸(Sorbic acid)、局部抗菌剂(thimerosal)等多种抗菌剂及抗真菌剂。另外,大部分情况下,所述注射剂还可以外加包括糖或氯化钠(Sodium Chloride)等等张剂。
如果采用经皮投入方式,则包括软膏、雪花膏、化妆水、凝胶、外用液剂、粉剂、擦剂(liniments)、气溶胶等形式。“经皮投入”是指吧药学合成物投入到皮肤表面,让药学合成物所含有效量活性成分传达到皮肤内的方式。而其制剂制造方式记录在制药化学领域的公开处方书——文献((Remington's Pharmaceutical Science,15th Edition,
1975,Mack Publishing Company,Easton,Pennsylvania))中。
如果采用吸入投入剂方式,则本发明的合成物使用适当的推进剂,比如使用二氯氟甲烷(Dichlorofluoromethane)、三氯氟甲烷(Trichlorofluoromethane)、二氯一氟乙烷(Dichlorofluoroethane)、二氧化碳或其他适合的气体进行加压,通过挤压或烟雾器(fogmachine),以气溶胶(aerosol)喷雾方式,方便地传达。如果采用加压气溶胶方式,可使用定量阀,决定投药单位。比如,用于吸入器或吹入器(insufflator)的明胶胶囊(gelatincapsule)及Cartridge以含化合物及乳糖(lactose)或淀粉等适合的粉末制剂粉末混合物的方式,制造成制剂。
之外,从药学上允许使用的载体可参考如下文献(Remington's PharmaceuticalSciences,19thed.,Mack Publishing Company,Easton,PA,1995)。
另外,本发明的药学合成物可以外加包括一种以上缓冲剂(比如,食盐水或PBS),碳水化合物(carbohydrate)(比如葡萄糖(glucose)、甘露糖(mannose)、(sucrose)或葡聚糖(dextran))。抗氧化剂,抑菌剂(fungistat),螯合剂(chelating agent)(比如EDTA或谷胱甘肽(glutathione)),佐剂(adjuvant)(比如,氢氧化铝alumin(i)um hydroxide),悬浊液,稠化剂(thickening agents)及/或保存剂。
进而,本发明提供的潘多汀派生物或提琴形凹唇姜萃取物可以具有促进肌肉增强及疲劳恢复、提高运动执行能力的食品合成物的形式。本发明的食品合成物包括功能食品(functional food)、营养辅助剂(nutritional supplement)、健康食品(health food)、食品添加剂(food additives)及饲料等一切形态,以人或包括家畜在内的动物为供食对象。所述类型的食品合成物,可按本行业公知的普通方法,以多样的形式制造。
比如,作为健康食品,把本发明的潘多汀派生物或提琴形凹唇姜萃取物本身制造成茶、汽水及酒(drink)等形式供应,或者进行颗粒化、胶囊化及粉末化供应。另外,本发明的潘多汀派生物或提琴形凹唇姜萃取物可与已公知的具促进肌肉增强及疲劳恢复功能、提高运动能力的其他活性成分混合,制造成合成物的形态。
另外,作为功能性食品,可把本发明的潘多汀派生物或提琴形凹唇姜萃取物添加到饮料(包括酒精饮料),水果及其加工食品(比如,水果罐头、瓶装罐头、果酱(jam)、橘子酱(marmalade)等),鱼类,肉类及其加工食品(比如:火腿、香肠等),面包类及面类(比如,乌冬面、荞麦面、拉面、意大利面、通心面等),果汁,各种酒(drink),曲奇饼,麦芽糖,乳制品(比如,黄油,乳酪等),食用植物油脂,人造黄油(margarine),植物蛋白,甑煮食品(retort food),冷冻食品,各种调味料(比如,大豆酱,酱油,调汁等),制造功能性食品。
另外,为了以食品添加剂的形式使用本发明的潘多汀派生物或提琴形凹唇姜萃取物,可以把其制造成粉末或浓缩液形态。
本发明的食品合成物中潘多汀派生物或提琴形凹唇姜萃取物的最佳含量为相对于食品总重,含0.01至100重量%。
另外,本发明的运动执行能力提高方法,其特征在于把潘多汀派生物或其盐以有效量投入到需要其的个体。同时本发明提供潘多汀派生物或其盐的用于制造提高运动执行能力制剂的用途。
另外,本发明的运动执行能力提高方法,其特征在于把提琴形凹唇姜萃取物以有效量投入到需要其的个体。同时本发明提供提琴形凹唇姜萃取物的用于制造提高运动执行能力制剂的用途。
另外,本发明的促进增加肌肉方法,其特征在于把潘多汀派生物或其盐以有效量投入到需要其的个体。同时本发明提供潘多汀派生物或其盐的用于制造促进增加肌肉制剂的用途。
另外,本发明的促进增加肌肉方法,其特征在于把提琴形凹唇姜萃取物以有效量投入到需要其的个体。同时本发明提供提琴形凹唇姜萃取物的用于制造促进增加肌肉制剂的用途。
另外,本发明的抗疲劳方法,其特征在于把潘多汀派生物或其盐以有效量投入到需要其的个体。同时本发明提供潘多汀派生物或其盐的用于制造抗疲劳制剂的用途。
另外,本发明的抗疲劳方法,其特征在于把提琴形凹唇姜萃取物以有效量投入到需要其的个体。同时本发明提供提琴形凹唇姜萃取物的用于制造抗疲劳制剂的用途。
本发明中,有效量是指本发明的潘多汀派生物或其盐或提琴形凹唇姜萃取物可在其投入对象个体内引起有效效果,即产生提高运动执行能力或促进增加肌肉或抗疲劳效果的量。所述个体(subject)是指哺乳动物,特别是包括人的动物。所述个体可以是需要提高运动执行能力或增加肌肉或抑制疲劳的个体。
发明效果
本发明的有益效果是提供含潘多汀派生物或其盐或提琴形凹唇姜萃取物的可促进肌肉增加、抗疲劳及提高运动执行能力的合成物(或方法、用途)。本发明的潘多汀派生物或提琴形凹唇姜萃取物无副作用,可安全使用,通过增加肌肉内的PPARδ的激活量,在增加肌肉、恢复疲劳及运动能力提高方面有非常优秀的效果。
附图说明
图1为高脂肪进食对照群,提琴形凹唇姜萃取物100mg/kg/day(KPE 100),提琴形凹唇姜萃取物200mg/kg/day(KPE 200),潘多汀A投入群(PAN50)的PPARδ蛋白质激活量检测结果。
图2为高脂肪进食对照群,提琴形凹唇姜萃取物100mg/kg/day(KPE 100),提琴形凹唇姜萃取物200mg/kg/day(KPE 200),潘多汀A投入群(PAN50)的肌肉量增加效果检测结果。
图3为高脂肪进食对照群,提琴形凹唇姜萃取物100mg/kg/day(KPE 100),提琴形凹唇姜萃取物200mg/kg/day(KPE 200),潘多汀A投入群(PAN50)的枯竭时间比较土,是运动能力增加效果检测结果。
具体实施方式
在此,参照实施例,对本发明进行详细说明。
这里需要说明的是下面的实施例只是本发明的实施例,本发明的内容不受限于下面的实施例。
<实施例1>
含潘多汀的提琴形凹唇姜萃取物的制造
把干燥好的提琴形凹唇姜萃取物,通过搅拌机(mixer)进行粉碎后,把100g粉碎的提琴形凹唇姜试料放入500mL乙醇中,在50℃条件下,搅拌三十分钟,进行萃取。把萃取的试料用沃特曼(Whatman)2号滤纸过滤,把过滤好的萃取液以真空旋转浓缩机浓缩、去除溶媒成分后,进行冻结干燥、去除水分,以此获得了提琴形凹唇姜萃取物。
<实施例2>
潘多汀A的分离及晶型结构
<2-1>潘多汀A的分离
从实施例1中得到的浓缩提琴形凹唇姜萃取物与乙酸乙酯(ethyl acetate)混合,萃取可溶于乙酸乙酯的成分,之后减压去除乙酸乙酯,浓缩了可溶于乙酸乙酯的成分。之后,把浓缩的成分放入到填充有615cm硅胶(silica gel)的圆柱(column)中,利用以15:5:1.5的比例混合己烷、氯仿(chloroform)、乙酸乙酯的溶媒体系,对其进行分取。所述分取按顺序总共划分为6个部分,分别对每个部分进行浓缩、干燥。6个部分中,对3号部分(部分3),以己烷、乙酸乙酯、甲醇比例为18:2:1(v/v/v)的展开剂,执行薄层分析法(TLC:Thin-Layer Chromatography)(TLC,silica gel 60F254,Merck),按分取的顺序、分为3哥部分进行浓缩、干燥。最终利用所述3个部分中的2号部分(部分32),进行循环(recycling)高效液相色谱法(ecycling HPLC,column:W252,20.0mmID500mm L),按分取顺序、划分为2个部分,对各福分进行了浓缩、干燥。最终,对所述2个部分中的2号部分(部分322)进行浓缩、干燥,分离了纯粹的单一活性物质。
<2-2>潘多汀A的晶型结构
为了实施例<2-1>分离的单一活性物质的晶型结构,分别以500MHz和125MHz(溶媒:CDCl3)条件,检测了1H-NMR光谱和13C-NMR光谱。以获得的13C-NMR光谱和1H-NMR广布的结果为基础,为了测定1H-1H的相关关系和1H-13C的相关关系,检测了1H-1H COSY光谱和1H-13CHSQC光谱,以通过碳原子共鸣输出的波长,区分各碳原子的信号,检测了其结果。
另外,为了对所述分离的单一物质进行质量分析,检测了EI/MS。本化合物在EI/MS上,在m/z 407观测到[M+H+],其分子量为406,分子式为C26H30O4。
以上1H-NMR、13C-NMR、1H-1H COSY、1H-13C HSQC及EI/MS的结果与原有的研究报告(Woo,W.S.et al.,Phytochemistry,26:15421543,1987)比较分析的结果,所述实施例<2-1>分离的单一物质是(2,6-二羟基-4-甲氧基苯基)[3-甲基-2-(3-甲基丁-2-烯基)-5-苯基环己胺-3-烯基]甲酮
【化学式1】
<实施例3>
提琴形凹唇姜萃取物与潘多汀A的PPAR蛋白质激活效果
让3周龄C57BL/6实验鼠适应1周,为了使之肥胖,供应7周高脂肪食料(Product#D12492,Research Diet Inc.,New Brunswick,NJ,USA)。待实验鼠肥胖后,以体重为基础,随机安排到各个群,每群8只,总分为3个群,用于实验。对于实验群,把潘多汀A及提琴形凹唇姜萃取物投入0.25%羧甲基纤维素(carboxy methylcellulose)溶液,形成悬浊液,潘多汀A以50mg/kg体重(PAN 50),提琴形凹唇姜萃取物以100mg/kg体重(KPE 100)、200mg/kg(KPE 200)体重两种浓度,每天1次,每天同一时间投入了8周。作为对照群,使用了摄取量与实验群相同,投入0.25%羧甲基纤维素和高脂肪食物的群。投入8周试料后,断食12小时以上,剖开腹部,取出肌肉组织,在-70℃条件下保管到实验前。从各群的各实验鼠分离的100mg肌肉,利用裂解液(lysis beffer)进行匀质化后,通过利用PPARδ抗体的蛋白质印迹(western blot)实验,进行了检测。
其结果如图1所示,与对照群相比,投入潘多汀A及提琴形凹唇姜萃取物的群,其PPARδ的激活量增加。PPARδ是I型骨骼肌纤维的转录因子,PPARδ的激活量增加时,I型骨骼肌纤维的量也会增加。另外,与KPE100投入群相比,KPE 200投入群的PPARδ激活量高。从而,可以得出结论,提琴形凹唇姜萃取物的PPARδ激活量调节作用与浓度有关。
<实施例4>
潘多汀的肌肉量增加效果
让3周龄C57BL/6实验鼠适应1周,为了使之肥胖,供应7周高脂肪食料(Product#D12492,Research Diet Inc.,New Brunswick,NJ,USA)。待实验鼠肥胖后,以体重为基础,随机安排到各个群,每群8只,总分为3个群,用于实验。对于实验群,把潘多汀A及提琴形凹唇姜萃取物投入到0.25%羧甲基纤维素(carboxy methylcel lulose)溶液,形成悬浊液,潘多汀A以50mg/kg体重(PAN 50),提琴形凹唇姜萃取物以100mg/kg体重(KPE 100)、200mg/kg(KPE 200)体重两种浓度,每天1次,每天同一时间投入了8周。作为对照群,使用了摄取量与实验群相同,投入0.25%羧甲基纤维素和高脂肪食物的群。投入8周试料后,利用微波-CT(Micro-computed tomography),对实验鼠的总体积及各组织的体积进行检测。
其结果,如图2所示,与对照群相比,投入潘多汀A及提琴形凹唇姜萃取物的群,肌肉的体积增加。投入提琴形凹唇姜萃取物的群肌肉量比对照群增加了2倍以上,这应该与肌肉内的PPARδ激活量增加有关。投入潘多汀A的群,其肌肉量也增加了1.88倍。
<实施例5>
跑步机(treadmill)实验
让3周龄C57BL/6实验鼠适应1周,为了使之肥胖,供应7周高脂肪食料(Product#D12492,Research Diet Inc.,New Brunswick,NJ,USA)。待实验鼠肥胖后,以体重为基础,随机安排到各个群,每群8只,总分为3个群,用于实验。对于实验群,把潘多汀A及提琴形凹唇姜萃取物投入到0.25%羧甲基纤维素(carboxy methylcellulose)溶液,形成悬浊液,潘多汀A以50mg/kg体重(PAN 50),提琴形凹唇姜萃取物以100mg/kg体重(KPE 100)、200mg/kg(KPE 200)体重两种浓度,每天1次,每天同一时间投入了8周。作为对照群,使用了摄取量与实验群相同,投入0.25%羧甲基纤维素和高脂肪食物的群。投入8周试料后,利用Exer-3R跑步机,以10%坡度,11m/min速度,检测了运动能力。
对电刺激条件下的运动时间进行检测的结果,如图3所示,投入提琴形凹唇姜萃取物200mg/kg体重(KPE 200)的群,与高脂肪食物对照群相比,显示了4.38倍运动能力提高效果。而投入提琴形凹唇姜萃取物100mg/kg体重(KPE 100)的群比对照群增加了2.92倍运动能力,投入潘多汀A(PAN 50)的群比对照群增加了2.77倍运动能力,这与KPE200相比,运动能力提高幅度略低。这与肌肉内PPARδ激活量实验结果一致,说明提琴形凹唇姜萃取物的运动能力增加效果与其浓度存在正相关关系。
工业利用可能性
综上所述,本发明提供含潘多汀派生物或其盐或提琴形凹唇姜萃取物的可促进肌肉增加、抗疲劳、提高运动执行能力的合成物。本发明的潘多汀派生物或提琴形凹唇姜萃取物无副作用,使用安全,通过提高肌肉内PPARδ的激活量,可以增加肌肉量、恢复疲劳、提高运动能力,其效果非常优秀。
Claims (21)
1.一种提高运动执行能力用合成物,其特征在于:其以有效成分含有潘多汀派生物或其盐。
3.根据权利要求1所述的提高运动执行能力用合成物,其特征在于:所述潘多汀派生物是从提琴形凹唇姜萃取的物质。
4.一种提高运动执行能力用合成物,其特征在于:其以有效成分含有提琴形凹唇姜萃取物。
5.根据权利要求1至4之一所述的提高运动执行能力用合成物,其特征在于:所述合成物是药学合成物或食品合成物。
6.一种肌肉增加促进用合成物,其特征在于:其以有效成分含有潘多汀派生物或其盐。
7.一种肌肉增加促进用合成物,其特征在于:其以有效成分含有提琴形凹唇姜萃取物。
8.一种抗疲劳用合成物,其特征在于:其以有效成分含有潘多汀派生物或其盐。
9.一种抗疲劳用合成物,其特征在于:其以有效成分含有提琴形凹唇姜萃取物。
10.一种运动执行能力提高方法,其特征在于:把潘多汀派生物或其盐以有效量投入到需要其的个体。
11.一种潘多汀派生物或其盐的用途,其特征在于:其用于制造运动执行能力提高用制剂。
12.一种运动执行能力提高方法,其特征在于:把提琴形凹唇姜萃取物以有效量投入到需要其的个体。
13.一种提琴形凹唇姜萃取物的用途,其特征在于:其用于制造运动执行能力提高用制剂。
14.一种增加肌肉促进方法,其特征在于:把潘多汀派生物或其盐以有效量投入到需要其的个体。
15.一种潘多汀派生物或其盐的用途,其特征在于:其用于制造增加肌肉促进用制剂。
16.一种增加肌肉促进方法,其特征在于:把提琴形凹唇姜萃取物以有效量投入到需要其的个体。
17.一种提琴形凹唇姜萃取物的用途,其特征在于:其用于制造增加肌肉促进用制剂。
18.一种抗疲劳方法,其特征在于:把潘多汀派生物或其盐以有效量投入到需要其的个体。
19.一种潘多汀派生物或其盐的用途,其特征在于:其用于制造抗疲劳用制剂。
20.一种抗疲劳方法,其特征在于:把提琴形凹唇姜萃取物以有效量投入到需要其的个体。
21.一种提琴形凹唇姜萃取物的用途,其特征在于:其用于制造抗疲劳用制剂。
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