CN107456467A - 锡兰七指蕨、入地蜈蚣素及黄酮类化合物用于治疗或预防新陈代谢疾病的用途 - Google Patents
锡兰七指蕨、入地蜈蚣素及黄酮类化合物用于治疗或预防新陈代谢疾病的用途 Download PDFInfo
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- CN107456467A CN107456467A CN201611186551.7A CN201611186551A CN107456467A CN 107456467 A CN107456467 A CN 107456467A CN 201611186551 A CN201611186551 A CN 201611186551A CN 107456467 A CN107456467 A CN 107456467A
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Abstract
本发明揭示一种锡兰七指蕨、入地蜈蚣素及式(I)化合物在治疗或预防新陈代谢疾病的用途，包括代谢症候群、脂肪过度储积、肥胖、体重过重、脂肪肝、肝性脂肪变性、肝炎、肝硬化、肝癌、血脂异常、高脂血症、高三酸甘油酯血症、高脂蛋白血症、高胆固醇血症、心血管疾病、高血糖症、高胰岛素血症、第二型糖尿病、胰岛素抗性、胰岛素失调、葡萄糖耐受不良及其组合所组成的群组的至少一种。
Description
技术领域
本发明关于一种中草药在治疗代谢疾病的用途，特别关于锡兰七指蕨及由其分离而得的入地蜈蚣素与式(I)化合物用于治疗或预防新陈代谢疾病的用途。
背景技术
目前已知肥胖和胰岛素失调与许多疾病间存在关联性，例如心血管疾病、第二型糖尿病、脂肪肝等等，这类疾病常涉及脂类代谢异常或糖类代谢异常。
举例而言，脂肪肝属于非酒精性脂肪肝疾病的初始阶段，是一种现代人常见的代谢症状，主要是由脂质代谢失衡所造成。目前已有为数不少的临床经验显示，脂肪肝会导致肝硬化，并且伴随着脂肪性肝炎及肝坏死等问题的发生。
目前，对于前述疾病及其他多种新陈代谢疾病，除了饮食控制及运动是最有效的预防及治疗方法外，现存的各种疗法仍未尽完美而存在某些待改善之处。
发明内容
本发明的主要目的之一，在于提供一种利用锡兰七指蕨治疗或预防新陈代谢疾病的用途，特别是锡兰七指蕨在制备用于治疗或预防新陈代谢疾病的药物的用途。
本发明的另一主要目的，在于提供一种利用入地蜈蚣素(ugonin)治疗或预防新陈代谢疾病的用途，特别是入地蜈蚣素在制备用于治疗或预防新陈代谢疾病的药物的用途。
本发明的再一主要目的，在于提供一种利用式(I)化合物或其医药可接受性盐类治疗或预防新陈代谢疾病的用途，特别是式(I)化合物或其医药可接受性盐类在制备用于治疗或预防新陈代谢疾病的药物的用途。其中，式(I)化合物的各个官能基团定义如后。
具体而言，该药物可以包含锡兰七指蕨的萃取物，例如但不限于锡兰七指蕨的根茎部的萃取物，例如锡兰七指蕨的根茎部的醇萃物，如乙醇萃取物。
前述新陈代谢疾病可以大致区分成代谢症候群、脂类代谢异常疾病及糖类代谢异常疾病等三大类，其中脂类代谢异常疾病选自于由脂肪过度储积、肥胖、体重过重、脂肪肝、肝性脂肪变性、肝炎、肝硬化、肝癌、血脂异常、高脂血症、高三酸甘油酯血症、高脂蛋白血症、高胆固醇血症、心血管疾病及其组合所组成的群组的至少一种，糖类代谢异常疾病选自于由高血糖症、高胰岛素血症、第二型糖尿病、胰岛素抗性、胰岛素失调、葡萄糖耐受不良及其组合所组成的群组的至少一种。
附图说明
图1A显示各组老鼠的体型及腰围；图1B显示各组老鼠的体重变化情形；图1C显示各组老鼠的每日摄食量；图1D显示各组老鼠的食物利用效率(FER)。
图2A显示各组老鼠的脂肪组织重量；图2B显示各组老鼠的脂肪细胞直径量测结果；图2C显示各组老鼠的脂肪细胞显微照片。
图3显示各组老鼠的血中三酸甘油酯(TG)、总胆固醇(TC)、HDL胆固醇(HDLC)及非HDL胆固醇含量。
图4A显示各组老鼠的肝脏重量、GOT、GPT及LIP浓度；图4B显示肝脏切片染色照片。
图5显示各组老鼠的空腹血糖值、空腹胰岛素值及胰岛素阻抗指数。
图6A显示各种入地蜈蚣素及锡兰七指蕨萃取物对于棕榈酸盐诱发的脂肪堆积的影响；图6B为人类肝细胞的油红O染色照片。
图7显示各种入地蜈蚣素对于PPAR-γ活性的影响。
图8显示各种入地蜈蚣素对于Akt活性的影响。
图9A显示入地蜈蚣素L对于人类肝细胞的AMPK活性的影响；图9B显示AMPK与ACC的磷酸化情形。
图10显示入地蜈蚣素对于BRIN-BD11细胞的葡萄糖刺激型胰岛素分泌的影响(比较基础为16.7mM葡萄糖)。
具体实施方式
本发明的主要方面在于发明人意外地发现锡兰七指蕨具有治疗或预防新陈代谢疾病的功效。
锡兰七指蕨为台湾民间常用的抗发炎草药，同时广泛用于中国大陆、东南亚、印度等地区。
于本文中，“锡兰七指蕨”是指一种七指蕨科(Helminthostachyaceae)的植物，其学名为Helminthostachys zeylanica(L.)Hook，简称为HZ，凡称为锡兰七指蕨、钉地蜈蚣、过路蜈蚣、地蜈蚣、倒麒麟、蜈蚣草等别名的植物，均属于本文所称的锡兰七指蕨。
若未特别指明，于本文提及锡兰七指蕨时，包含锡兰七指蕨的全株植物、此植物的任何一部分或此植物的多部分混合物，且其形式可以是植物株或其一或多部分、干燥物、研磨物、熬煮物、萃取物等任何一种适于投予接受者或患者(包括含人类在内的所有动物)的型态，例如口服型态。
举例而言，可将锡兰七指蕨制成萃取物，例如浓缩产物及干燥产物，以自其中萃取具有生物活性的物质，如入地蜈蚣素。若未特别指明，萃取方法、萃取溶剂、萃取组份或萃取类型并不特别限制，可为中草药领域中习知者。例如，可将锡兰七指蕨的根茎部或其他部分制成乙醇萃取物。
于一实施例中，“治疗”是指任何一种有利于人类或非人类动物的疗程、处理或疗法，包括疾病(或症状)的治愈、缓和或预防。若未特别指明，治疗方式包括投予需要者一治疗有效量的前述锡兰七指蕨、其萃取物、入地蜈蚣素、式(I)化合物或其医药可接受性盐类。治疗有效量可为例如每人每天至少3g科学中药(以习知方式制成)，或每人每天至少一两水药(以习知方式制成)，其中“科学中药”及“水药”具有本领域普通技术人员所了解的一般意义。
于一实施例中，具体而言，“治疗”一词可指获得所需的药理及/或生理效果，该效果可为预防性，例如完全或部分预防疾病或其症状；或可为治疗性，例如对疾病可达成部分或完全治愈；或可对于疾病有反向影响。
于本文中，“治疗”一词涵盖哺乳动物内的任何疾病治疗，尤其是人类的任何疾病治疗，且包含：(a)预防疾病不要在有疾病倾向的主体内发生，即使主体尚未被诊断为患有该疾病；(b)抑制疾病，即遏止其发展；以及(c)缓和疾病，也就是让疾病消退。
“治疗有效量”指利用本文所述的前述锡兰七指蕨、其萃取物、入地蜈蚣素、式(I)化合物或其医药可接受性盐类或医药组成物在主体中治疗或预防疾病或失调的剂量。化合物的组成物较佳为协同组成物，协同作用如同本领域技术人员所知，代表发生于化合物共同投药时的效用大于化合物个别投药时的加乘作用。一般而言，协同效果大多清楚显现于化合物的次最适浓度。相较于个别成分的作用，协同作用可降低细胞毒性、增加活性或者获得组成物的某些其他有利效果。
于一实施例中，“预防”是指任何一种有利于人类或非人类动物的预防性处理，通常于疾病或症状形成或发展前进行，也可于疾病或症状形成或发展中进行。
若未特别指明，“预防”和“治疗”涵盖各种为了处理、降低、抑制、舒缓、调节、减缓、控制疾病或症状所采取的措施。
于本文中，新陈代谢疾病包括但不限于先天及后天代谢异常，例如代谢症候群、脂类代谢异常疾病及糖类代谢异常疾病。
代谢症候群的范围涵盖以下危险因子：(1)腹部肥胖，例如腰围男性≥90cm、女性≥80cm；(2)高血压，例如收缩血压(SBP)≥130mmHg、舒张血压(DBP)≥85mmHg；(3)高血糖，例如空腹血糖值(FG)≥100mg/dl；(4)高密度脂蛋白胆固醇(HDL-C)例如男性<40mg/dl、女性<50mg/dl；(5)高三酸甘油酯(TG)例如≥150mg/dl。
脂类代谢异常疾病包括因为饮食失调(例如高脂或高糖饮食)所造成的代谢疾病以及非饮食失调所造成的代谢疾病，脂类代谢异常疾病的实例包括但不限于脂肪过度储积、肥胖、体重过重、脂肪肝、肝性脂肪变性、肝炎、肝硬化、肝癌、血脂异常、高脂血症、高三酸甘油酯血症、高脂蛋白血症、高胆固醇血症、心血管疾病及其组合。
糖类代谢异常疾病包括因为饮食失调(例如高脂或高糖饮食)所造成的代谢疾病以及非饮食失调所造成的代谢疾病，糖类代谢异常疾病的实例包括但不限于高血糖症、高胰岛素血症、第二型糖尿病、胰岛素抗性、胰岛素失调、葡萄糖耐受不良及其组合。
本发明的另一个方面在于发明人意外地发现入地蜈蚣素(ugonin)具有治疗或预防新陈代谢疾病的功效。前述入地蜈蚣素(ugonin)可以是分离自例如锡兰七指蕨或得自其他来源，也可以是以人为方式化学合成者。
发明人发现，入地蜈蚣素对于调节饮食引发的新陈代谢疾病有显著的效果，例如可用于预防、治疗、抑制或减缓各种新陈代谢疾病，因此具有开发成药物、植物药、保健食品或健康食品的潜力。举例而言，可将含有多种入地蜈蚣素的植物，例如锡兰七指蕨进行萃取，得到包含两种以上入地蜈蚣素的萃取物。为能使萃取物特定一或多种的入地蜈蚣素含量提高，可根据本领域习知的萃取因素及条件调整萃取的方式。
若未特别指明，本发明提到的入地蜈蚣素包括至少入地蜈蚣素A至入地蜈蚣素U，共计21种，且其中较优选者包括例如入地蜈蚣素J、入地蜈蚣素K、入地蜈蚣素L、入地蜈蚣素M、入地蜈蚣素O、入地蜈蚣素T，更优选者包括前述任两种或多种的混合物。
藉由活体内及活体外实验，发明人咸信入地蜈蚣素可以调控以下生物分子的任何一种或多种的活性：PPAR-γ(peroxisome proliferator-activated receptor gamma)、Akt(protein kinase B)、AMPK(AMP-activated protein kinase)、ACC(acetyl-CoAcarboxylase)、SREBP1(sterol regulatory element-binding protein 1)、FAS(fattyacid synthase)、FOXO1(forkhead box protein O1)、CPT1(carnitinepalmitoyltransferase I)或ATGL(adipose triglyceride lipase)，因此可用于制备用于预防或治疗受到PPAR-γ、Akt、AMPK、ACC、SREBP1、FAS、FOXO1、CPT1或ATGL调控影响的新陈代谢疾病药物，包括但不限于代谢症候群、脂肪过度储积、肥胖、体重过重、脂肪肝、肝性脂肪变性、肝炎、肝硬化、肝癌、血脂异常、高脂血症、高三酸甘油酯血症、高脂蛋白血症、高胆固醇血症、心血管疾病、高血糖症、高胰岛素血症、第二型糖尿病、胰岛素抗性、胰岛素失调、葡萄糖耐受不良及其组合所组成的群组的至少一种。
本发明的又一个方面在于发明人发现以下式(I)化合物或其医药可接受性盐类在制备用于预防或治疗新陈代谢疾病的药物的用途，例如代谢症候群、脂肪过度储积、肥胖、体重过重、脂肪肝、肝性脂肪变性、肝炎、肝硬化、肝癌、血脂异常、高脂血症、高三酸甘油酯血症、高脂蛋白血症、高胆固醇血症、心血管疾病、高血糖症、高胰岛素血症、第二型糖尿病、胰岛素抗性、胰岛素失调、葡萄糖耐受不良及其组合所组成的群组的至少一种。
其中，代表单键或双键；R1选自H、OH或OC1-C6烷基，或R1与R9形成一含氧杂环；R2为H，或R2与R3形成一含氧杂环；R3选自H或取代或未取代的C1-C6伸烷基C3-C6环烃基，或R3与R2形成一含氧杂环，或R3与R4形成一含氧杂环；R4选自H或C1-C6烷基，或R4与R3形成一含氧杂环，或R4与R5形成一含氧杂环；R5选自H或C1-C6烷基取代的C2-C6烯基，或R5与R4形成一含氧杂环；R6选自H或取代或未取代的C1-C6伸烷基C3-C6环烃基，或R6与R7形成一含氧杂环；R7选自H、OH或OC1-C6烷基，或R7与R6形成一含氧杂环；R8选自H或OH；且R9为H，或R9与R1形成一含氧杂环。
于本文中，用语“医药可接受性盐类”是指一种离子性化合物，其中非毒性原化合物经修饰后可制成其酸式盐类或碱式盐类。医药可接受性盐类的实例包括如胺类作为碱性基团的无机酸盐类或有机酸盐类、如羧酸作为酸性基团的碱金属或有机盐类以及前述盐类的类似物。医药可接受性盐类包括如由非毒性无机或有机酸形成的原化合物的已知非毒性盐类及四级铵盐类。
前述盐类可包括衍生自盐酸、氢溴酸、氢碘酸、硫酸、氨基磺酸、磷酸、硝酸与类似酸类的无机酸的盐类。由有机酸制得的盐类中，该有机酸可包括醋酸、2–乙酰氧基苯甲酸、抗坏血酸、苯磺酸、苯甲酸、柠檬酸、乙烷磺酸、乙烷二磺酸、甲酸、延胡索酸、龙胆酸、醛糖酸、葡萄糖酸、麸氨酸、乙醇酸、羟基马来酸、羟乙基磺酸、异烟碱酸、乳酸、马来酸、苹果酸、甲磺酸、草酸、泛酸、苯乙酸、丙酸、水杨酸、磺胺酸、对甲苯磺酸、硬脂酸、琥珀酸、酒石酸、双酒石酸及类似酸类，特定化合物亦可形成具有各种氨基酸的医药可接受性盐类。
本文所述化合物的医药可接受性盐类可从含碱性或酸性基团的化合物利用已知化学方法合成。一般而言，于水或有机溶剂或其两者的混合液中，经由该化合物的游离酸或碱形式与化学剂量的适当碱或酸反应即可制备此等盐类，一般非水性媒介可为例如醚、乙酸乙酯、乙醇、异丙醇或乙腈。
前述一或多种式(I)化合物或其医药可接受性盐类可以医药组成物的形式存在，即包含式(I)化合物或其医药可接受性盐类的组成物或组合物，其并包括一种医药上可接受的载剂，例如可供共同投药的稀释剂、佐剂或赋形剂。此种载剂可为液体(如水及油)、盐水或其类似物。此外，可搭配使用助剂、稳定剂、增稠剂、润滑剂及着色剂等。于本文中，医药可接受载剂或赋形剂包括但不限于填充剂、粘合剂、分解剂、润滑剂以及其他有利于将本发明的化合物或其医药可接受性盐类投药至接受者的任何成分。
于本文中，若以一范围界定特定数量时，该范围应解读为包括范围的两端点值、范围内的所有子范围以及范围内的所有数值。举例而言，范围C1-C4应包括C1、C2、C3、C4以及C1-C2、C1-C3、C1-C4、C2-C3、C2-C4、C3-C4。
于本文中，OC1-C6烷基即为C1-C6烷氧基。
用语“烷基”表示含有直链、二级、三级或环碳原子的烃基，例如可为甲基、乙基、1-丙基、2-丙基、1-丁基、2-甲基-1-丙基、2-丁基、叔丁基、1-戊基、2-戊基、3-戊基、2-甲基-2-丁基、3-甲基-2-丁基、3-甲基-1-丁基、2-甲基-1-丁基、1-己基、2-己基、3-己基、2-甲基-2-戊基、3-甲基-2-戊基、4-甲基-2-戊基、3-甲基-3-戊基、2-甲基-3-戊基、2,3-二甲基-2-丁基、3,3-二甲基-2-丁基等等。烷基可为单价烃基团或为二价烃基团(即伸烷基)。
用语“烷氧基”表示-O-烷基的基团，其中烷基定义如上所述。较佳的烷氧基包括例如甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、叔丁氧基、仲丁氧基、正戊氧基、正己氧基、1,2-二甲基丁氧基等。
于本文中，含氧杂环可以是具有氧杂原子的环状结构或基团，例如含有氧原子的五元杂环、含有氧原子的六元杂环、含有氧原子的七元杂环等等，且不限于此。此外，前述含氧杂环可以是独立的基团(非稠合)或与其他环状基团结合(稠合)。
于本文中，环烃基可以是例如多个碳原子组成的环状烃基，例如环烷基或环烯基，其可具有单环或多环缩合环。环烷基包括，举例而言，单环结构例如为环丙基、环丁基、环戊基、环辛基等。
除非另有指明，否则各种式(I)化合物的立体异构体均包含在本发明的范畴内。换言之，本发明的式(I)化合物包含其原子空间排列不同的异构体，如镜像异构体及非镜像异构体均属之，其中不对称经取代的碳原子作为手性中心。可使用符号R及S代表手性碳原子周围取代基的构形。
于一实施例中，式(I)化合物的R1选自H、OH或OC1-C3烷基。
于一实施例中，式(I)化合物的R2为H。
于一实施例中，式(I)化合物的R3选自H或取代或未取代的C1-C3伸烷基C5-C6环烃基。
于一实施例中，式(I)化合物的R4选自H或C1-C3烷基，或R4与R5形成一含氧杂环。
于一实施例中，式(I)化合物的R5选自H或C1-C3烷基C2-C4烯基。
于一实施例中，式(I)化合物的R6为H。
于一实施例中，式(I)化合物的R7选自H、OH或OC1-C3烷基。
于一实施例中，式(I)化合物的R8选自H或OH。
于一实施例中，式(I)化合物的R9为H。
具体而言，式(I)化合物可包含以下化合物的任一种或多种：
2-(3,4-二羟基苯基)-5-羟基-12,12-二甲基-8,8a,9,10,11,12,12a,13-八氢-4H-苯并[5,6]氧杂环庚三烯并[2,3-h]苯并哌喃-4-酮；
5-羟基-2-(4-羟基-3-甲氧基苯基)-12,12-二甲基-8,8a,9,10,11,12,12a,13-八氢-4H-苯并[5,6]氧杂环庚三烯并[2,3-h]苯并哌喃-4-酮；
5-羟基-2-(4-羟基苯基)-3-甲氧基-8,9,9-三甲基-8,9-二氢-4H-呋喃并[2,3-h]苯并哌喃-4-酮；
5-羟基-2-(4-羟基苯基)-8,9,9-三甲基-2,3,8,9-四氢-4H-呋喃并[2,3-h]苯并哌喃-4-酮；
(R)-5,7-二羟基-2-(4-羟基苯基)-8-(2-甲基丁-3-烯-2-基)-2,3-二氢苯并哌喃-4-酮；
3,5-二羟基-2-(4-羟基苯基)-8,9,9-三甲基-8,9-二氢-4H-呋喃并[2,3-h]苯并哌喃-4-酮；
(S)-3,5,7-三羟基-2-(4-羟基苯基)-6-((2,6,6-三甲基环己-2-烯-1-基)甲基)-4H-苯并哌喃-4-酮；
(S)-2-(3,4-二羟基-2-((2,6,6-三甲基环己-2-烯-1-基)甲基)苯基)-5,7-二羟基-3-甲氧基-4H-苯并哌喃-4-酮；
5,7-二羟基-2-((4aS,9aR)-5-羟基-1,1,4a-三甲基-2,4a,9,9a-四氢-1H-二苯并哌喃-8-基)-3-甲氧基-4H-苯并哌喃-4-酮；
(R)-2-(3,4-二羟基苯基)-6-((2,2-二甲基-6-亚甲基环己基)甲基)-5,7-二羟基-4H-苯并哌喃-4-酮；
(R)-2-(3,4-二羟基苯基)-6-((2,2-二甲基-6-亚甲基环己基)甲基)-5-羟基-7-甲氧基-4H-苯并哌喃-4-酮；
(7aR,11aS)-3-(3,4-二羟基苯基)-6-甲氧基-8,8,11a-三甲基-7a,8,9,10,11,11a-六氢-1H,7H-哌喃并[2,3-c]二苯并哌喃-1-酮；
1,3,7,8-四氢-6-((2,6,6-三甲基环己-2-烯-1-基)甲基)-11H-苯并呋喃并[3,2-b]苯并哌喃-11-酮；
3,5,7-三羟基-2-((4aS,9aR)-5-羟基-1,1,4a-三甲基-2,3,4,4a,9,9a-六氢-1H-二苯并哌喃-8-基)-4H-苯并哌喃-4-酮；
(4aS,15aR)-6,10,12-三羟基-1,1,4a-三甲基-2,4a,15,15a-四氢苯并哌喃[2',3':4,5]呋喃并[3,2-a]二苯并哌喃-9(1H)-酮；
(S)-2-(3,4-二羟基苯基)-5,7-二羟基-6-((2,6,6-三甲基环己-2-烯-1-基)甲基)-4H-苯并哌喃-4-酮；
2-(3,4-二羟基苯基)-5,7-二羟基-6-(((1S,5S)-5-羟基-2,2-二甲基-6-亚甲基环己基)甲基)-4H-苯并哌喃-4-酮；
2-(3,4-二羟基苯基)-5,7-二羟基-6-(((1S)-2-羟基-2,6,6-三甲基环己基)甲基)-4H-苯并哌喃-4-酮；
(7aR,11aS)-3-(3,4-二羟基苯基)-6-羟基-8,8,11a-三甲基-7a,8,9,10,11,11a-六氢-1H,7H-哌喃并[2,3-c]二苯并哌喃-1-酮；
7-(3,4-二羟基苯基)-4-羟基-2,3,3-三甲基-2,3-二氢-5H-呋喃并[3,2-g]苯并哌喃-5-酮；
(6aS,10aR)-2-(3,4-二羟基苯基)-5-羟基-7,7,10a-三甲基-6a,7,8,9,10,10a-六氢-4H,6H-哌喃并[3,2-b]二苯并哌喃-4-酮。
本发明的再一个方面在于提供一种包含前述锡兰七指蕨、入地蜈蚣素、式(I)化合物或其医药可接受性盐类的医药组合物，可用于治疗或预防新陈代谢疾病，例如同时治疗或预防与饮食型态相关的多种新陈代谢疾病，包括代谢症候群、脂类代谢异常疾病及糖类代谢异常疾病。
包含一或多种剂量单位的本发明成分的医药组合物的传递形式，为可使用本领域技术人员已知晓或可利用的医药赋形剂及调配技术进行制备。所述制备物可为锭剂、胶囊、冲剂、糖衣锭、粉剂、颗粒剂、口含锭、用于重组的粉末、液体制剂或栓剂的形式。
本发明的医药组合物可供口服投药，例如以锭剂或胶囊的形式提供，或是溶液、乳液或悬浮液。
口服锭剂可包含根据本发明的成分混合药学上可接受的赋形剂，例如惰性稀释剂、崩解剂、黏合剂、润滑剂、甜味剂、调味剂、着色剂及防腐剂。合适的惰性填充剂包含碳酸钠和碳酸钙、磷酸钠和磷酸钙、乳糖、淀粉、糖、葡萄糖、甲基纤维素、硬脂酸镁、甘露醇、山梨醇及其类似物。
用于口服投药的胶囊包含硬式及软式明胶胶囊。欲制备硬式明胶胶囊，可将本发明的成分和固体、半固体或液体的稀释剂混合。软式明胶胶囊可藉由将本发明的成分与水、油(如花生油或橄榄油)、液态石蜡、短链脂肪酸的单或双甘油酯的混合物、聚乙二醇400或丙二醇混合而制备。
用于口服投药的液体可为悬浮液、溶液、乳液或糖浆的形式，或者可被冻干或以干式产物存在而于使用前和水或其他合适的媒剂重组。
此类液体组成物可视需要包含：药学上可接受的赋形剂，例如悬浮剂(如山梨醇、甲基纤维素、海藻酸钠、明胶、羟乙基纤维素、羧甲基纤维素、硬脂酸铝凝胶及其类似物)；非水性媒剂，例如油(如杏仁油或椰子油)、丙二醇、乙醇或水；防腐剂(如对羟苯甲酸甲酯或丙酯或山梨酸)；润湿剂，例如卵磷脂；以及调味剂或着色剂。
实施例：锡兰七指蕨萃取物的制备
自中药材行购得锡兰七指蕨，并与卫生福利部国家中医药研究所标本馆所保存的样本(NRICM-99-003)进行比对确认。取锡兰七指蕨的根茎部计531g，利用2.5L的EtOH-H2O(1:1，2.5L x 3)在回流条件下进行加热1小时，之后将滤液浓缩并冷冻干燥，以获得锡兰七指蕨萃取物计29g。
实施例：入地蜈蚣素的制备
将所得锡兰七指蕨萃取物利用HPLC法进行分离纯化，可以得到例如入地蜈蚣素K、入地蜈蚣素O、入地蜈蚣素M、入地蜈蚣素J等化合物。此外，可参照习知方法制备例如入地蜈蚣素L、入地蜈蚣素T及其他入地蜈蚣素。由于各种入地蜈蚣素，例如入地蜈蚣素A至入地蜈蚣素U共计21种，均可由现有文献公开的方法制备或分离而得，在此不另赘述。
实施例：实验动物准备
自乐斯科生物科技股份有限公司购得30只4周大的C57BL/6J雄鼠。依照一般实验动物饲养方式，将其饲养于恒温、12小时光暗循环的条件下，之后分成三组，分别为正常饮食组(简称ND组，共10只，给予一般饮食)、高脂饮食组(简称HFD组，共10只，食物中给予30重量％脂肪及1重量％胆固醇)、实验组(简称HZ组，共10只，给予和HFD组相同的食物，并额外添加0.5重量％的锡兰七指蕨萃取物)，并饲养12周以进行实验。
于实验结束后，使老鼠禁食12小时，之后采集分析样本，包括自后大静脉采血，以量测血糖、血中脂肪及特定酶浓度。依照一般组织或器官采集流程，取出肝脏及脂肪组织，用生理食盐水润洗、称重、液态氮冷冻、保存至分析。
首先，图1A显示12周后各组老鼠的体型及腰围；图1B显示12周期间各组老鼠的体重变化情形；图1C显示各组老鼠的每日摄食量；图1D显示各组老鼠的食物利用效率(foodefficiency ratio，FER，即体重增加量除以摄食量)。
由图1A至图1D可以看出，锡兰七指蕨萃取物有利于控制体重、抑制肥胖并降低食物利用效率，且锡兰七指蕨萃取物并未明显影响摄食量或食欲。
实施例：肝脏及脂肪组织型态观察
将肝脏及副睪脂肪组织(EAT)样本以10体积％的聚甲醛/PBS固定，嵌入石蜡中并以苏木精及伊红染色，以显微镜在200倍的倍率下观察染色区域。
图2A显示各组老鼠的脂肪组织重量；图2B显示各组老鼠的脂肪细胞直径量测结果；图2C显示各组老鼠的脂肪细胞显微照片。
由图2A至图2C可以看出，锡兰七指蕨萃取物有利于降低脂肪组织重量并控制脂肪细胞的大小。
实施例：肝及血清中脂质
使用FUJI DRI-CHEM分析仪及酶试剂盒量测血中三酸甘油酯(TG)、总胆固醇(TC)、HDL胆固醇(HDLC)、谷氨酸草酰乙酸转氨酶(GOT)、谷氨酸丙酮酸转氨酶(GPT)及脂肪酶(LIP)等生物分子浓度，并依照公式[(总胆固醇)-(HDLC)-(TG/5)]计算非HDL胆固醇浓度。
图3显示各组老鼠的血中三酸甘油酯(TG)、总胆固醇(TC)、HDL胆固醇(HDLC)及非HDL胆固醇含量。可以看出，锡兰七指蕨萃取物有利于降低三酸甘油酯、总胆固醇及非HDL胆固醇含量，但对于HDL胆固醇的影响则较不明显。
图4A显示各组老鼠的肝脏重量、GOT、GPT及LIP状态。可以看出，锡兰七指蕨萃取物有利于控制或抑制肝脏重量增加，实验组老鼠的肝指数GOT及GPT也明显降低，且其肾脏酶脂肪酶LIP浓度并未受到明显影响，代表锡兰七指蕨萃取物并无肾毒性。图4B显示肝脏切片染色照片，可以看出实验组HZ的肝脏脂肪堆积情形明显低于对照组HFD。
实施例：血糖、血中胰岛素及胰岛素阻抗指数
在实验期间，每隔两周采集老鼠尾部静脉血量测禁食12小时的血糖浓度，并利用酶分析法量测血中胰岛素浓度，以下式计算胰岛素阻抗指数(HOMA-IR)：[空腹胰岛素(mU/L)×空腹血糖(mg/dL)×0.05551]/22.5。
图5显示各组老鼠的空腹血糖值、空腹胰岛素值及胰岛素阻抗指数。可以看出实验组HZ从第六周开始空腹血糖值即明显低于对照组，且空腹胰岛素值也显著降低，胰岛素阻抗指数明显下降，代表胰岛素抗性降低。
实施例：人类肝细胞培养及处理
将人类肝细胞利用肝细胞培养液进行培养，以棕榈酸盐/BSA复合物的形式提供不同浓度的棕榈酸盐至培养基，以提供过量的脂肪酸，并观察锡兰七指蕨萃取物与不同入地蜈蚣素对于细胞的影响。此外，为了观察胞内脂肪含量，将细胞进行油红O染色，依照一般染色条件进行样本制备，并量测510nm的吸光值以计算细胞脂肪含量。
图6A显示各种入地蜈蚣素及锡兰七指蕨萃取物对于棕榈酸盐诱发的脂肪堆积的影响，图6B为人类肝细胞的油红O染色照片，可以看出各种入地蜈蚣素在20μM及锡兰七指蕨萃取物在100μg/ml浓度下对于脂肪堆积均有明显的抑制作用。
实施例：PPAR-γ活性测试
使用市售PPAR-γ转录因子分析试剂盒对人类肝细胞进行处理，并量测450nm的吸光值以评估不同入地蜈蚣素对于PPAR-γ活性的影响。
图7显示各种入地蜈蚣素对于PPAR-γ活性的影响，可以看出大部分入地蜈蚣素在20μM浓度下均可增进PPAR-γ活性。由于此受体主要表现于脂肪组织且被认为涉及脂肪生成的调控，且目前此受体的促效剂如thiazolidinedione类化合物有利于减缓第二型糖尿病病患的高血糖症、高胰岛素血症、高三酸甘油酯血症，因此图7的数据代表各种入地蜈蚣素有利于治疗或预防脂类代谢异常疾病或糖类代谢异常疾病。
实施例：Akt激酶活性测试
使用市售Akt分析试剂盒对人类肝细胞进行处理，搭配蛋白质印迹法评估GSK3-α的磷酸化情形，间接评估不同入地蜈蚣素对于Akt活性的影响。
图8为Akt分析试剂盒的蛋白质印迹照片，显示各种入地蜈蚣素对于Akt活性的影响，可以看出入地蜈蚣素(特别是入地蜈蚣素J)可促进Akt活性，显示入地蜈蚣素有利于血糖代谢的调控。
实施例：AMPK活化测试
目前已知AMPK是调节脂肪酸合成的关键生物分子，AMPK在Thr-172位置的磷酸化可中止脂肪酸合成，且已知例如metformin与thiazolidinedione类药物减缓人类脂肪肝的机转均涉及AMPK的活化及脂肪代谢的向下调节。
将人类肝细胞利用PH培养液进行培养，控制组不加入0.1mM棕榈酸盐，对照组加入0.1mM棕榈酸盐但不添加入地蜈蚣素L，其余四组实验组加入0.1mM棕榈酸盐及2.5、5、10及20μM入地蜈蚣素L，之后进行蛋白质印迹分析。图9A为人类肝细胞的AMPK蛋白质印迹活性测试结果，显示入地蜈蚣素L对于人类肝细胞的AMPK活性的影响；图9B显示AMPK与ACC的磷酸化情形，可以看出2.5、5、10及20μM的入地蜈蚣素L均可显著提高AMPK的磷酸化，且伴随着ACC在Ser-79位置磷酸化的提升，显示入地蜈蚣素L诱发AMPK磷酸化进而抑制ACC活性。
实施例：促进胰岛素分泌测试
将大鼠胰脏β细胞株BRIN-BD11于培养皿中以单细胞层形式进行生长，生长条件为温度37℃、5％CO2/空气、90％湿度，使用的培养液为RPMI 1640，其包含10％胎牛血清及5％的青霉素与链霉素混合物。
之后将BRIN-BD11细胞移置于24孔盘内(0.5×105细胞/孔)，并于包含5.6mM葡萄糖浓度的培养液中培养48小时。在进行急性胰岛素分泌测试前，先将细胞于1.1mM的葡萄糖溶液(使用Krebs-Ringer重碳酸盐缓冲液)中在37℃条件下培养45分钟。接着以DMSO媒液或各种入地蜈蚣素在16.7mM葡萄糖溶液中(使用Krebs-Ringer重碳酸盐缓冲液)处理20分钟，之后收集培养基内物质以进行胰岛素分析，以均相时间分辨荧光分析法(HTRF)进行胰岛素浓度定量分析，并将结果正规化至总细胞数为一百万的水平。
所有资料均以平均值±标准差的方式呈现，使用的统计分析工具为GraphPadPrism(GraphPad,CA,USA)，使用非成对学生t检验得出单一参数比较结果，其中P值小于0.05及0.01即视为具有统计显著性。
如图10所示，从葡萄糖反应型胰岛素分泌细胞株BRIN-BD11的分析结果中，可以观察到入地蜈蚣素对于BRIN-BD11细胞的胰岛素分泌情形所造成的潜在影响。于实验过程中，Exendin-4(EX-4)作为胰岛素促进剂而当成阳性对照组，结果显示入地蜈蚣素C、F、J、K、M及T在低于20μM的浓度下即可显著地促进BRIN-BD11细胞在16.7mM葡萄糖存在下(高血糖条件)的胰岛素分泌。
实施例：细胞存活试验
在完成急性胰岛素分泌测试后，于盘中的空孔内加入50μg/ml的中性红(Neutralred)溶液并培养2小时，之后移除培养液并以酸乙醇溶解细胞，以光谱分析法在540nm波长下定量细胞内溶酶体摄入中性红的情形。
从存活试验结果中发现，在添加入地蜈蚣素进行急性胰岛素分泌测试后，并未观察到有显著的毒性，所有试剂处理后的细胞存活率均高于95％。
据此，于前述说明中，发明人已充分描述关于特定实施例及实例的概念。然应了解的是，本领域普通技术人员可在不偏离权利要求书所界定的范畴下进行各种变化、改变及修饰。因此，于解读权利要求时，应将本发明的发明说明以说明性而非限制性的方式作为参考，且前述各种变化、改变及修饰均应涵盖于本发明的范围内。
此外，本文所述各实施例中的某些特征，亦可以组合的方式于单独实施例中加以提供，且各别实施例亦可分别提供或以任何次组合的方式提供之。此外，范围内描述的相关数值应包括所述范围内的每个数值。
Claims (16)
1.一种锡兰七指蕨在制备用于治疗或预防新陈代谢疾病的药物的用途。
2.如权利要求1所述的用途，其中该药物包含锡兰七指蕨的萃取物。
3.如权利要求2所述的用途，其中该萃取物为锡兰七指蕨的根茎部的醇萃物。
4.如权利要求1所述的用途，其中该新陈代谢疾病为代谢症候群、脂类代谢异常疾病或糖类代谢异常疾病。
5.如权利要求4所述的用途，其中该脂类代谢异常疾病选自于由脂肪过度储积、肥胖、体重过重、脂肪肝、肝性脂肪变性、肝炎、肝硬化、肝癌、血脂异常、高脂血症、高三酸甘油酯血症、高脂蛋白血症、高胆固醇血症、心血管疾病及其组合所组成的群组的至少一种。
6.如权利要求4所述的用途，其中该糖类代谢异常疾病选自于由高血糖症、高胰岛素血症、第二型糖尿病、胰岛素抗性、胰岛素失调、葡萄糖耐受不良及其组合所组成的群组的至少一种。
7.一种入地蜈蚣素(ugonin)在制备用于调节饮食引发的新陈代谢疾病的药物的用途。
8.如权利要求7所述的用途，其中该药物用于预防、治疗、抑制或减缓该新陈代谢疾病。
9.如权利要求7所述的用途，其中该入地蜈蚣素选自于由入地蜈蚣素J、入地蜈蚣素K、入地蜈蚣素L、入地蜈蚣素M、入地蜈蚣素O、入地蜈蚣素T及其组合所组成的群组的至少一种。
10.一种入地蜈蚣素(ugonin)在制备用于预防或治疗受到PPAR-γ、Akt、AMPK、ACC、SREBP1、FAS、FOXO1、CPT1或ATGL调控影响的新陈代谢疾病的药物的用途。
11.如权利要求10所述的用途，其中该新陈代谢疾病选自于由代谢症候群、脂肪过度储积、肥胖、体重过重、脂肪肝、肝性脂肪变性、肝炎、肝硬化、肝癌、血脂异常、高脂血症、高三酸甘油酯血症、高脂蛋白血症、高胆固醇血症、心血管疾病、高血糖症、高胰岛素血症、第二型糖尿病、胰岛素抗性、胰岛素失调、葡萄糖耐受不良及其组合所组成的群组的至少一种。
12.一种式(I)化合物或其医药可接受性盐类在制备用于预防或治疗新陈代谢疾病的药物的用途，
其中，
代表单键或双键；
R1选自H、OH或OC1-C6烷基，或R1与R9形成一含氧杂环；
R2为H，或R2与R3形成一含氧杂环；
R3选自H或取代或未取代的C1-C6伸烷基C3-C6环烃基，或R3与R2形成一含氧杂环，或R3与R4形成一含氧杂环；
R4选自H或C1-C6烷基，或R4与R3形成一含氧杂环，或R4与R5形成一含氧杂环；
R5选自H或C1-C6烷基取代的C2-C6烯基，或R5与R4形成一含氧杂环；
R6选自H或取代或未取代的C1-C6伸烷基C3-C6环烃基，或R6与R7形成一含氧杂环；
R7选自H、OH或OC1-C6烷基，或R7与R6形成一含氧杂环；
R8选自H或OH；且
R9为H，或R9与R1形成一含氧杂环。
13.如权利要求12所述的用途，其中R1选自H、OH或OC1-C3烷基；R2为H；R3选自H或取代或未取代的C1-C3伸烷基C5-C6环烃基；R4选自H或C1-C3烷基，或R4与R5形成一含氧杂环；R5选自H或C1-C3烷基C2-C4烯基；R6为H；R7选自H、OH或OC1-C3烷基；R8选自H或OH；且R9为H。
14.如权利要求12所述的用途，其中该式(I)化合物选自于由：
2-(3,4-二羟基苯基)-5-羟基-12,12-二甲基-8,8a,9,10,11,12,12a,13-八氢-4H-苯并[5,6]氧杂环庚三烯并[2,3-h]苯并哌喃-4-酮；
5-羟基-2-(4-羟基-3-甲氧基苯基)-12,12-二甲基-8,8a,9,10,11,12,12a,13-八氢-4H-苯并[5,6]氧杂环庚三烯并[2,3-h]苯并哌喃-4-酮；
5-羟基-2-(4-羟基苯基)-3-甲氧基-8,9,9-三甲基-8,9-二氢-4H-呋喃并[2,3-h]苯并哌喃-4-酮；
5-羟基-2-(4-羟基苯基)-8,9,9-三甲基-2,3,8,9-四氢-4H-呋喃并[2,3-h]苯并哌喃-4-酮；
(R)-5,7-二羟基-2-(4-羟基苯基)-8-(2-甲基丁-3-烯-2-基)-2,3-二氢苯并哌喃-4-酮；
3,5-二羟基-2-(4-羟基苯基)-8,9,9-三甲基-8,9-二氢-4H-呋喃并[2,3-h]苯并哌喃-4-酮；
(S)-3,5,7-三羟基-2-(4-羟基苯基)-6-((2,6,6-三甲基环己-2-烯-1-基)甲基)-4H-苯并哌喃-4-酮；
(S)-2-(3,4-二羟基-2-((2,6,6-三甲基环己-2-烯-1-基)甲基)苯基)-5,7-二羟基-3-甲氧基-4H-苯并哌喃-4-酮；
5,7-二羟基-2-((4aS,9aR)-5-羟基-1,1,4a-三甲基-2,4a,9,9a-四氢-1H-二苯并哌喃-8-基)-3-甲氧基-4H-苯并哌喃-4-酮；
(R)-2-(3,4-二羟基苯基)-6-((2,2-二甲基-6-亚甲基环己基)甲基)-5,7-二羟基-4H-苯并哌喃-4-酮；
(R)-2-(3,4-二羟基苯基)-6-((2,2-二甲基-6-亚甲基环己基)甲基)-5-羟基-7-甲氧基-4H-苯并哌喃-4-酮；
(7aR,11aS)-3-(3,4-二羟基苯基)-6-甲氧基-8,8,11a-三甲基-7a,8,9,10,11,11a-六氢-1H,7H-哌喃并[2,3-c]二苯并哌喃-1-酮；
1,3,7,8-四氢-6-((2,6,6-三甲基环己-2-烯-1-基)甲基)-11H-苯并呋喃并[3,2-b]苯并哌喃-11-酮；
3,5,7-三羟基-2-((4aS,9aR)-5-羟基-1,1,4a-三甲基-2,3,4,4a,9,9a-六氢-1H-二苯并哌喃-8-基)-4H-苯并哌喃-4-酮；
(4aS,15aR)-6,10,12-三羟基-1,1,4a-三甲基-2,4a,15,15a-四氢苯并哌喃[2',3':4,5]呋喃并[3,2-a]二苯并哌喃-9(1H)-酮；
(S)-2-(3,4-二羟基苯基)-5,7-二羟基-6-((2,6,6-三甲基环己-2-烯-1-基)甲基)-4H-苯并哌喃-4-酮；
2-(3,4-二羟基苯基)-5,7-二羟基-6-(((1S,5S)-5-羟基-2,2-二甲基-6-亚甲基环己基)甲基)-4H-苯并哌喃-4-酮；
2-(3,4-二羟基苯基)-5,7-二羟基-6-(((1S)-2-羟基-2,6,6-三甲基环己基)甲基)-4H-苯并哌喃-4-酮；
(7aR,11aS)-3-(3,4-二羟基苯基)-6-羟基-8,8,11a-三甲基-7a,8,9,10,11,11a-六氢-1H,7H-哌喃并[2,3-c]二苯并哌喃-1-酮；
7-(3,4-二羟基苯基)-4-羟基-2,3,3-三甲基-2,3-二氢-5H-呋喃并[3,2-g]苯并哌喃-5-酮；
(6aS,10aR)-2-(3,4-二羟基苯基)-5-羟基-7,7,10a-三甲基-6a,7,8,9,10,10a-六氢-4H,6H-哌喃并[3,2-b]二苯并哌喃-4-酮；
及其组合所组成的群组的至少一种。
15.如权利要求12所述的用途，其中该式(I)化合物选自于由：
(R)-2-(3,4-二羟基苯基)-6-((2,2-二甲基-6-亚甲基环己基)甲基)-5,7-二羟基-4H-苯并哌喃-4-酮；
(R)-2-(3,4-二羟基苯基)-6-((2,2-二甲基-6-亚甲基环己基)甲基)-5-羟基-7-甲氧基-4H-苯并哌喃-4-酮；
(7aR,11aS)-3-(3,4-二羟基苯基)-6-甲氧基-8,8,11a-三甲基-7a,8,9,10,11,11a-六氢-1H,7H-哌喃并[2,3-c]二苯并哌喃-1-酮；
1,3,7,8-四氢-6-((2,6,6-三甲基环己-2-烯-1-基)甲基)-11H-苯并呋喃并[3,2-b]苯并哌喃-11-酮；
(4aS,15aR)-6,10,12-三羟基-1,1,4a-三甲基-2,4a,15,15a-四氢苯并哌喃[2',3':4,5]呋喃并[3,2-a]二苯并哌喃-9(1H)-酮；
7-(3,4-二羟基苯基)-4-羟基-2,3,3-三甲基-2,3-二氢-5H-呋喃并[3,2-g]苯并哌喃-5-酮；
及其组合所组成的群组的至少一种。
16.如权利要求12所述的用途，其中该新陈代谢疾病选自于由代谢症候群、脂肪过度储积、肥胖、体重过重、脂肪肝、肝性脂肪变性、肝炎、肝硬化、肝癌、血脂异常、高脂血症、高三酸甘油酯血症、高脂蛋白血症、高胆固醇血症、心血管疾病、高血糖症、高胰岛素血症、第二型糖尿病、胰岛素抗性、胰岛素失调、葡萄糖耐受不良及其组合所组成的群组的至少一种。
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| CN104812399A (zh) * | 2012-09-17 | 2015-07-29 | 韩国原子力研究院 | 包含蜈蚣草提取物或其部位作为活性成分的组合物 |
| TWI524892B (zh) * | 2014-03-28 | 2016-03-11 | 嘉藥學校財團法人嘉南藥理大學 | Ugonin 化合物用以製備抗皮膚發炎之組成物之用途 |
| TWI549677B (zh) * | 2014-03-31 | 2016-09-21 | 嘉藥學校財團法人嘉南藥理大學 | Ｕｇｏｎｉｎ化合物於製備治療皮膚癌藥物之用途 |
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| CN104812399A (zh) * | 2012-09-17 | 2015-07-29 | 韩国原子力研究院 | 包含蜈蚣草提取物或其部位作为活性成分的组合物 |
| TWI524892B (zh) * | 2014-03-28 | 2016-03-11 | 嘉藥學校財團法人嘉南藥理大學 | Ugonin 化合物用以製備抗皮膚發炎之組成物之用途 |
| TWI549677B (zh) * | 2014-03-31 | 2016-09-21 | 嘉藥學校財團法人嘉南藥理大學 | Ｕｇｏｎｉｎ化合物於製備治療皮膚癌藥物之用途 |
Non-Patent Citations (3)
| Title |
|---|
| ACHLIYA, GIRISH S , ET AL.: ""Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats"", 《JOURNAL OF ETHNOPHARMACOLOGY》 * |
| HUANG, YAUN CHAO , ET AL.: ""Anti-inflammatory Flavonoids from the Rhizomes of Helminthostachys zeylanica"", 《JOURNAL OF NATURAL PRODUCTS》 * |
| 杨明等: ""蜂胶总黄酮对STZ诱导糖尿病大鼠降血糖机制研究"", 《中药材》 * |
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