CN105935364A - 用于预防或治疗非酒精性肝病的包含人参皂苷f2的组合物 - Google Patents
用于预防或治疗非酒精性肝病的包含人参皂苷f2的组合物 Download PDFInfo
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- CN105935364A CN105935364A CN201610121723.6A CN201610121723A CN105935364A CN 105935364 A CN105935364 A CN 105935364A CN 201610121723 A CN201610121723 A CN 201610121723A CN 105935364 A CN105935364 A CN 105935364A
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Abstract
本发明涉及一种用于预防、改善或治疗非酒精性肝病或胰岛素抵抗性的人参皂苷F2的药物组合物、健康功能食品及饲料组合物。本发明的包含人参皂苷F2的药物组合物可抑制在肝内形成及堆积脂肪，提高胰岛素敏感度，在库普弗细胞中抑制如TNF‑α、IL‑1β及IL‑6的炎症性细胞因子的表达，抑制内源性大麻素合成酶的表达而有效地预防或治疗非酒精性肝病或胰岛素抵抗性。
Description
技术领域
本发明涉及一种用于预防、改善或治疗非酒精性肝病或胰岛素抵抗性的人参皂苷F2的药物组合物、健康功能食品及饲料组合物。
背景技术
肝是在人体内负责各种代谢作用、解毒、分解、合成及分泌的非常重要的脏器，其具体功能如下：第一，肝具有管理能量代谢的功能，将从食物中吸收的所有营养素代谢为可生产能量的物质并供给或储存到全身。第二，肝具有对约2000余种的酶、白蛋白、凝血因子的血清蛋白、胆汁酸、磷脂质、胆固醇等的脂肪进行合成、储存及分配的功能。第三，肝具有通过胆管向十二指肠排泄各种代谢产物的功能，且具有免疫功能，因此在维持生命方面发挥重要作用。最后，肝具有解毒及分解功能，对药物、毒性物质、酒精等进行解毒。但是，肝的这种解毒功能容易损伤肝细胞，从而会诱发药物性、毒性、非酒精性肝病等。
另一方面，曾报告人参皂苷F2在乳腺癌干细胞(CSCs)中进行自体吞噬(autophagy)的同时杀灭细胞，从而在乳腺癌中表现出抗癌效果(Mai TT et al.2012；28；321(2)：144-53)，在SD大鼠的异种移植模型中，人参皂苷F2对胶质母细胞瘤表现出抗癌效果(Shin JY et al.2012；36(1)：86-92)。另外，已知可将人参皂苷F2用作去皱、美白或祛痘用化妆原料组合物(韩国公开专利2014-0013795)。然而，未曾揭示人参皂苷F2治疗非酒精性肝病的效果。
在这种背景下，本发明人等为了开发用于治疗非酒精性肝病及胰岛素抵抗性的方法而进行锐意研究，结果确认到如下情况而完成了本发明：可从人参中提取的人参皂苷F2不仅可缓解胰岛素抵抗性、保护肝免受非酒精性肝损伤，而且还可抑制肝内中性脂肪的形成、堆积及炎症，从而可用于预防或治疗各种非酒精性肝损伤或胰岛素抵抗性的用途。
发明内容
[发明要解决的问题]
本发明的一目的在于提供一种用于预防或治疗非酒精性肝病或胰岛素抵抗性的包含人参皂苷F2的药物组合物。
本发明的另一目的在于提供一种用于预防或改善非酒精性肝病或胰岛素抵抗性的包含人参皂苷F2的健康功能食品。
本发明的又一目的在于提供一种用于预防或改善非酒精性肝病或胰岛素抵抗性的包含人参皂苷F2的饲料组合物。
本发明的又一目的在于提供一种包含向个体投用所述药物组合物的步骤的非酒精性肝病或胰岛素抵抗性的预防或治疗方法。
[解决问题的手段]
为了达成所述目的，作为一实施方式，本发明提供一种用于预防或治疗非酒精性肝病或胰岛素抵抗性的包含人参皂苷F2的药物组合物。本发明的人参皂苷F2可用于制备用以预防或治疗非酒精性肝病或胰岛素抵抗性的医药的用途。
人参皂苷F2作为以下述化学式1表示的四环系原人参二醇(protopanaxadiol，PPD)皂苷，是吸收及药效相对出色于主要皂苷的次要皂苷中的一种。
[化学式1]
在本发明中，人参皂苷F2可使用市售的人参皂苷F2、从在自然界中栽培或摘取的人参分离的人参皂苷F2、或从所分离出的人参皂苷转化的人参皂苷F2。或者，可使用通过合成方法而合成的人参皂苷F2，只要为表现出本发明的预防或治疗非酒精性肝病的效果的人参皂苷F2，则可无限制地使用。
所述非酒精性肝病是指除因饮酒过量所导致的酒精性肝病以外的肝病。在本发明中，非酒精性肝病包含非酒精性脂肪肝、非酒精性肝炎或非酒精性肝硬变，优选为包含非酒精性脂肪肝，但并不限制于此。
肝炎是指肝细胞及肝组织的炎症，如果因慢性肝炎而长期反复破坏肝细胞并再生的过程，则肝内的纤维组织与再生结节增加而演变为肝硬变或肝硬化。如果肝硬变发展到一定等级以上，则可诱发肝性脑病(Hepatic encephalopathy)、食道静脉曲张(Esophageal varix)等并发症。
脂肪肝(fatty liver)是指肝中堆积有大于在正常的肝中脂肪所占的比例(5％)的脂肪，非酒精性脂肪肝(non-alcoholic fatty liver disease，NAFLD)是未刻意摄取酒精而在肝内堆积脂肪的疾病。
所述非酒精性脂肪肝从因肝细胞内堆积中性脂肪所致的单纯脂肪肝(fatty liver)到伴随炎症反应的脂肪性肝炎(non-alcoholic steatohepatitis，NASH)、肝硬化包含广泛的演变过程。作为一例，可包含因肝内各种损伤过程的相互作用所引起的炎症反应、及由此导致的肝纤维化。作为这种肝损伤的原因，有氧化应激、由细胞因子引起的肝损伤、由游离脂肪酸引起的肝毒性、非正常胆固醇的增加、高胰岛素血症、细胞死亡等。所述脂肪肝尤其可为因糖尿病、高血脂症或药物等引起的非酒精性脂肪肝。
如果肝炎与肝硬变伴随出现，则会发生呈肝的合成及解毒功能下降的状态的肝功能不全。
所述肝病可为通过天冬氨酸转氨酶(Aspartate Transaminase，AST)、丙氨酸转氨酶(Alanine Transaminase，ALT)、碱性磷酸酶(Alkaline Phosphatase，ALP)、γ-谷酰基转移酶(Gamma Glutamyl Transferase，GGT)或胆红素(Bilirubin)来诊断的疾病。
在本发明中，术语“胰岛素抵抗性”是因细胞及组织对胰岛素的感受性下降而胰岛素效果减少的状态的统称，本发明的包含人参皂苷F2的组合物可预防、治疗或改善所述胰岛素抵抗性。
在本发明的具体的一实施例中，确认到如下情况：人参皂苷F2在肝细胞中抑制因高脂肪饮食增加的脂肪合成基因SREBP1c与FAS的表达，且抑制在肝内堆积脂肪(图2a至图2d)。因此，人参皂苷F2在肝细胞、肝星状细胞中抑制脂肪合成的效果优异，具体而言，确认到如下情况：人参皂苷F2抑制非酒精性介质即内源性大麻素的产生，阻碍相邻的肝细胞内的CB1R信号传输，由此抑制在肝内形成及堆积脂肪。另外，确认到人参皂苷F2在进行高脂肪饮食的小鼠中改善胰岛素抵抗性的效果(图3a及图3b)。因此，本发明的包含人参皂苷F2的药物组合物可有效地预防、治疗因在肝内形成或堆积脂肪引起的非酒精性肝病及胰岛素抵抗性。
本发明人等确认到进行12周高脂肪饮食的小鼠的肝的大小及质量实质性地减少(图1a及图1b)，且通过肝组织的H&E及油红O(Oil Red O)染色确认到脂肪减少(图2)。
另外，确认到如下情况：在肝细胞及肝星状细胞中抑制调节堆积脂肪的路径的转录因子即SREBP1c与FAS、在肝细胞内脂肪合成中发挥重要作用的CB1R、诱导脂肪合成的内源性大麻素合成酶DAGL-α、DAGL-β的表达增加，减少脂肪酸水解酶FAAH及与脂肪合成相关的基因即NAPE-PLD的表达(图2及图5)，由此人参皂苷F2可预防或抑制在肝内形成及堆积脂肪而有效地预防或治疗肝病。
进而，本发明人等确认到与未投用人参皂苷F2的小鼠相比，投用人参皂苷F2的小鼠的胰岛素敏感度提高的效果(图3)，且确认到人参皂苷F2在长期进行高脂肪饮食的小鼠的肝组织及肝细胞中使如肿瘤坏死因子-α(Tumor Necrosis Factor-α，TNF-α)、白细胞介素-1β(Interleukin-1β，IL-1β)及IL-6的炎症性细胞因子的表达减少(图4)。
因此，人参皂苷F2可改善胰岛素抵抗性，可减少炎症性细胞因子的表达而缓解非酒精性肝病及由此导致的肝损伤。
作为一例，所述人参皂苷F2可相对于药物组合物的总重量包含0.01至100重量％，更优选为可包含1至80重量％。
本发明中所使用的术语“预防”可指向个体投用本发明的人参皂苷F2而抑制或延缓非酒精性肝病的发病或胰岛素抵抗性的所有行为。
本发明中所使用的术语“治疗”可指向非酒精性肝病发病或胰岛素抵抗性疑似个体投用本发明的所述组合物而使肝病症状好转或受益的所有行为。
本发明的药物组合物可作为单一制剂来使用，还可加添公认的具有非酒精性肝病治疗效果的药物而制备成复合制剂来使用，可通过利用在药学上容许的载体或赋形剂来制剂化而制备成单位容量形态或装入到多容量容器内制备。
本发明中所使用的术语“在药学上可容许的载体”可指既不刺激生物体又不阻碍所注入的化合物的生物学活性及特性的载体或稀释剂。在本发明中可使用的所述载体的类型并无特别限制，可使用在本技术领域中普遍使用且药学上容许的任一载体。作为所述载体的非限定性的例，可列举食盐水、灭菌水、林格氏液、缓冲食盐水、白蛋白注射溶液、葡萄糖溶液、麦芽糖糊精溶液、甘油、乙醇等。这些可单独使用或混合两种以上来使用。所述载体可包含非自然载体(non-naturally occuring carrier)。另外，可视需要添加抗氧化剂、缓冲液及/或抑菌剂等其他普通的添加剂来使用，还可加添稀释剂、分散剂、表面活性剂、结合剂、润滑剂等而制剂化成水溶液、悬浊液、乳浊液等注射用剂型、丸剂、胶囊、颗粒或片剂等来使用。
另外，本发明的药物组合物可包含在药学上有效的量的人参皂苷F2。在本发明中，术语“在药学上有效的量”是指足以按照可应用于医学治疗的合理的受益/危险比例治疗疾病的量，通常每天可分1次至数次投用如下量：0.001至1000mg/kg，优选为0.05至200mg/kg，更优选为0.1至100mg/kg。然而，根据本发明的目的，针对特定患者的具体治疗有效量优选为根据所要达成的反应的类型及程度、是否视情况使用其他制剂等具体组合物、患者的年龄、体重、通常健康状态、性别及饮食、投用时间、投用路径及组合物的分泌率、治疗期间、与具体组合物一同使用或同时使用的药物等各种因子与在医学领域中公知的类似因子来采用不同的应用方式。
本发明的药物组合物可作为单个治疗剂来投用，或者可与其他治疗剂并用，也可与以往的治疗剂依次或同时投用。而且，可单一投用或多重投用。重要的是考虑所有所述要素而投用既不会诱发副作用又能够以最少的量达到最大效果的量，这可由本领域技术人员容易地确定。
本发明中所使用的术语“投用”是指采用某种适当的方法向患者导入本发明的药物组合物，只要可到达靶组织则本发明的组合物的投用路径可为口服或非口服的各种路径。
本发明的药物组合物的投用方式并无特别限制，可采用在本技术领域中普遍使用的方法。作为所述投用方式的非限定性的例，可采用口服或非口服方式投用组合物。本发明的药物组合物可与投用方式对应地制备成各种剂型。
本发明的组合物的投用频率并无特别限制，可一天投用一次或分量投用多次。
作为又一实施方式，本发明提供一种包含向非酒精性肝病或胰岛素抵抗性疑似个体投用所述组合物的步骤的非酒精性肝病或胰岛素抵抗性的预防或治疗方法。作为一例，提供一种包含向除人类以外的非酒精性肝病或胰岛素抵抗性疑似个体投用所述组合物的步骤的非酒精性肝病的预防或治疗方法。
人参皂苷F2、非酒精性肝病及胰岛素抵抗性与上述内容相同。
本发明中所使用的术语“个体”可指包含已诱发非酒精性肝病或存在发病可能性的人类在内的所有动物。所述动物不仅为人类，而且还可为需要治疗与此类似的症状的牛、马、绵羊、猪、山羊、骆驼、羚羊、狗、猫等哺乳动物，但并不限制于此。
具体而言，本发明的所述预防或治疗方法可包含以造药学上有效的量向已诱发非酒精性肝病或存在发病危险的个体投用所述组合物的步骤。
作为又一实施方式，本发明提供一种用于预防或改善非酒精性肝病或胰岛素抵抗性的包含人参皂苷F2的健康功能食品。本发明的人参皂苷F2可用于制备用以改善非酒精性肝病或胰岛素抵抗性的健康功能食品的用途。
人参皂苷F2、非酒精性肝病及胰岛素抵抗性与上述内容相同。
所述人参皂苷F2是可从人参、白参、山参等中提取的天然物质，其稳定性在长期使用过程中得到认可，因此可制备成既可日常服用又可预防或改善非酒精性肝病或胰岛素抵抗性的食品形态来摄取。
健康功能食品(functional food)是与特定保健用食品(food for special health use，FoSHU)相同的术语，指除供给营养以外还可有效地呈现生物体调节功能的经加工的医学、医疗效果明显的食品，为了获得有利于非酒精性肝病或胰岛素抵抗性的预防或改善的效果，所述食品可制备成片剂、胶囊、粉末、颗粒、口服液、丸剂等各种形态。
此时，所述健康功能食品所含的人参皂苷F2的含量并无特别限制，但可相对于健康功能食品的总重量而包含0.01至100重量％，更优选为包含1至80重量％。
本发明的食品组合物可追加包含在食品学上可容许的载体。
可添加本发明的包含人参皂苷F2的组合物的食品种类并无特别限制，例如有各种饮料、口香糖、茶、维生素复合剂、健康辅助食品类等。在所述食品组合物中可添加不妨碍非酒精性肝病或胰岛素抵抗性的预防或改善效果的其他成分，其种类并无特别限制。例如，可像普通的食品一样含有各种生药提取物、在食品学上可容许的食品辅助添加剂或天然碳水化合物等作为补充成分。
所述食品辅助添加剂是在制备各种剂型的健康功能食品时添加的添加剂，可由本领域技术人员适当地选择使用。例如，包含各种营养剂、维生素、矿物质(电解质)、合成调味剂及天然调味剂等调味剂、着色剂及填充剂、果胶酸及其盐、褐藻酸及其盐、有机酸、保护性凝胶增粘剂、pH值调节剂、稳定剂、防腐剂、甘油、乙醇、使用在碳酸饮料中的碳酸化剂等，但其种类并不限制于所述例。
此时，包含在所述食品的人参皂苷F2的含量并无特别限制，但可相对于食品组合物的总重量而包含0.01至100重量％，更优选为包含1至80重量％。
在食品为饮料的情况下，能够以100Ml为基准而按照1至30g的比例包含，优选为按照3至20g的比例包含。另外，所述组合物可包含通常使用在食品组合物中而提升气味、味道、视觉效果等的补充成分。例如，可包含维生素A、维生素C、维生素D、维生素E、维生素B1、维生素B2、维生素B6、维生素B12、烟酸(niacin)、生物素(biotin)、叶酸(folate)、泛酸(panthotenic acid)等。另外，可包含锌(Zn)、铁(Fe)、钙(Ca)、铬(Cr)、镁(Mg)、锰(Mn)、铜(Cu)等矿物质。另外，可包含赖氨酸、色氨酸、半胱氨酸、缬氨酸等氨基酸。另外，可添加防腐剂(山梨酸钾、苯甲酸钠、水杨酸、脱氢乙酸钠等)、杀菌剂(漂白粉和高度漂白粉、次氯酸钠等)、抗氧化剂(丁基羟基茴香醚(BHA)、二丁基羟基甲苯(BHT)等)、着色剂(煤焦油色素等)、固色剂(亚硝酸钠、亚醋酸钠等)、漂白剂(亚硫酸钠)、调料(MSG谷氨酸钠等)、甜味剂(甘素、甜蜜素、糖精、钠等)、香料(香草醛、内酯类等)、膨胀剂(明矾、D-酒石酸钾等)、强化剂、乳化剂、增粘剂(糊料)、覆膜剂、胶基、抑泡剂、溶剂、改良剂等食品添加物(food additives)。根据食品的种类选择所述添加物并适量使用。
本发明的健康功能食品可通过在本技术领域中常用的方法来制备，在制备所述健康功能食品时，可添加在本技术领域中普遍添加的原料及成分来制备。另外，其余普通的药物不同地以食品为原料，具有不存在因长期服用药物引起的副作用等优点，且便携性优异。
作为又一实施方式，本发明提供一种用于预防或改善非酒精性肝病或胰岛素抵抗性的包含人参皂苷F2的饲料用组合物。本发明的人参皂苷F2可用于制备用以预防或改善非酒精性肝病或胰岛素抵抗性的饲料的用途。
人参皂苷F2、非酒精性肝病及胰岛素抵抗性与上述内容相同。
所述饲料用组合物可包含饲料添加剂。本发明的饲料添加剂为饲料管理法中所规定的辅助饲料。
在本发明中，术语“饲料”可指供动物食用、摄取及消化或与此相应的任意天然或人工规定餐、定量餐等或所述定量餐的成分。
所述饲料的种类并无特别限制，可使用本技术领域中普遍使用的饲料。作为所述饲料的非限定性的例，可列举如谷物类、根果类、食品加工副产物类、藻类、纤维质类、制药副产物类、油脂类、淀粉类、瓢类或谷物副产物类等植物性饲料；如蛋白质类、无机物类、乳脂类、矿物性类、单细胞蛋白质类、动物性浮游生物类或食物等动物性饲料。这些可单独使用或混合两种以上来使用。
[发明的效果]
本发明的包含人参皂苷F2的药物组合物可抑制在肝内形成及堆积脂肪，提高胰岛素敏感度，在库普弗细胞中抑制如TNF-α、IL-1β及IL-6的炎症性细胞因子的表达，抑制内源性大麻素合成酶的表达而有效地预防或治疗非酒精性肝病或胰岛素抵抗性。
附图说明
图1a及图1b是确认人参皂苷F2对进行高脂肪饮食的小鼠的脂肪肝的缓解效果的图。Veh是从进行生理食盐水处理的对照组小鼠分离的肝，GF2是从进行人参皂苷F2处理的小鼠分离的肝(以下相同)。
图2a至图2d是确认进行高脂肪饮食的小鼠的肝的脂肪形成程度的图。
图3a及图3b是确认人参皂苷F2的提高胰岛素敏感度的效果的图。
图4a及图4b是确认人参皂苷F2抑制炎症性细胞因子的表达的效果的图。
图5是表示人参皂苷F2在肝星状细胞中抑制NAPE-PLD、FAAH、DAGLα及DAGLβ的表达的效果的图。
图6是表示人参皂苷F2保护肝免患脂肪肝及胰岛素抵抗性的机制。
具体实施方式
以下，通过实施例详细地对本发明进行说明。这些实施例仅用于例示本发明，不应解释为本发明的范围限制于这些实施例。
实施例1.人参皂苷F2的制备
将包含高丽参、花旗参、竹节参在内的其他人参的叶及根放入到其20倍体积的80％酒精中，提取两次以上并进行干燥而获得粗皂苷。将所述粗皂苷再次溶解于水，并使其吸附到HP-20树脂后，使用100％水进行清洗而去除糖，之后使用40％酒精进行一次清洗而优先去除作为原人参三醇(protopanaxatriol)系的人参皂苷Re与Rg1。此后，如果使用80％酒精进行清洗，则溶出作为原人参二醇(protopanaxadiol)系的人参皂苷Rb1、Rb2、Rc、Rd，对其进行干燥而获得所述人参皂苷F2。将所述原人参二醇人参皂苷混合物用作基质，按照韩国公开专利第2013-0134930号中记载的方法使其反应而获得70％以上的人参皂苷F2。此后，如果使用ODS树脂吸附将用作试样的人参皂苷F2后，按照浓度梯度连续滴加适当的浓度的酒精，则可获得纯度高至95％以上的人参皂苷F2馏分，对其进行干燥而使用。
实施例2：确认脂肪肝缓解效果
为了确认人参皂苷F2的脂肪肝缓解效果，利用进行高脂肪饮食的小鼠模型。对8周大的雄性小鼠(体重为25～28g)连续进行12周的高脂肪饮食，并按照每周5天使小鼠口服250mg/kg的人参皂苷F2。
此后，分离肝并进行观察，结果确认到如下情况：与对照组相比，使用人参皂苷F2的组的肝的大小(图1a)与肝的重量(图1b)差明显减少。通过所述结果可知，即便进行高脂肪饮食，人参皂苷F2仍具有抑制脂肪肝的效果。
实施例3：肝组织分析
为了观察所述实施例2的进行高脂肪饮食的小鼠的肝组织变化，执行H&E(Hematoxylin and eosin)染色，通过油红O(Oil Red O)染色对肝细胞的中性脂质进行染色，以×100的倍率表示所述结果(图2a)。其结果，可再次确认到因投用人参皂苷F2而脂肪在肝细胞中的堆积减少。
另外，确认到如下情况：肝内中性脂肪(Liver TG)数值下降(图2b)，在脂肪合成中发挥重要作用的因子即SREBP1c、FAS的蛋白表达与CB1R、NAPE-PLD、SREBP1c、FAS基因表达的水平降低(图2c及图2d)。因此，可确认到人参皂苷F2在肝有效地抑制脂肪形成。
实施例4：确认胰岛素敏感度的提高
当所述实施例2的进行高脂肪饮食的小鼠发育到11周大时，向其投用葡萄糖与胰岛素，之后按时检测血糖。其结果，可确认到如下情况：与对照组相比，人参皂苷F2组的血糖值随着时间的增加而下降，相比于初期血糖而血糖降低效果优异(图3)。综上可知，人参皂苷F2在进行高脂肪饮食的小鼠中具有提高胰岛素敏感度的效果。
实施例5：确认炎症性细胞因子表达的抑制
人参皂苷F2在进行高脂肪饮食及服入人参皂苷F2的小鼠中抑制各种炎症性细胞因子(TNF-α、IL-1β及IL-6)的表达，在库普弗细胞中也表现出与此相同的结果(图4)。
因此，可知人参皂苷F2在进行高脂肪饮食的小鼠中抑制库普弗细胞的炎症性细胞因子的表达而缓解肝的炎症。
实施例6：确认在肝星状细胞中抑制内源性大麻素合成酶表达
在对肝星状细胞进行TNF-α处理后，处理10μM、20μM及30μM的人参皂苷F2并培养24小时。在所培养的肝星状细胞中确认表达水平的差异，结果可确认到如下情况：人参皂苷F2抑制在作为内源性大麻素的一种的2-AG的合成中发挥重要作用的酶即DAGLα及DAGLβ的表达，除此以外，还抑制与肝损伤相关的因子即NAPE-PLD、FAAH的表达(图5)。
综上可知，人参皂苷F2在肝星状细胞中抑制内源性大麻素合成酶的表达。
综合所述实施例，人参皂苷F2在库普弗细胞中抑制炎症性细胞因子(TNF-α、IL-1β及IL-6)的表达，且在肝星状细胞中抑制内源性大麻素(DAGLα及DAGLβ)的合成。另外，在肝细胞的情况下，通过人参皂苷F2抑制SREBP1c、FAS、CB1R及NAPE-PLD等与脂肪合成相关的基因的表达而缓解肝损伤。对此，在图6中以图表方式表示人参皂苷F2保护肝免患脂肪肝及胰岛素抵抗性的机制。因此，本发明的包含人参皂苷F2的组合物可有效地用于预防、治疗及改善非酒精性肝病或胰岛素抵抗性的用途。
根据以上说明，本发明所属技术领域内的技术人员应可理解，在不变更本发明的技术思想或必要特征的前提下，能够以其他具体方式实施本发明。与此相关，应理解为以上所记述的实施例在所有方面均为示例，并不限定本发明。本发明的范围应解释为并不限定于以上详细的说明，从随附的权利要求书的含义、范围及其等效概念导出的所有变更或变形的形态均包含在本发明的范围内。
Claims (6)
1.一种人参皂苷F2的用途，其用于制备用以治疗非酒精性肝病或胰岛素抵抗性的药物。
2.根据权利要求1所述的用途，其中所述非酒精性肝病为非酒精性脂肪肝、非酒精性肝炎或非酒精性肝硬变。
3.根据权利要求1所述的用途，其中所述人参皂苷F2抑制在肝内形成或堆积脂肪。
4.一种人参皂苷F2的用途，其用于制备用以改善非酒精性肝病或胰岛素抵抗性的健康功能食品。
5.根据权利要求4所述的用途，其中所述健康功能食品为粉末、颗粒、片剂、胶囊或饮料形态。
6.一种人参皂苷F2的用途，其用于制备用以改善非酒精性肝病或胰岛素抵抗性的饲料。
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| CN114729337A (zh) * | 2019-05-22 | 2022-07-08 | 德美崔克斯公司 | 优化的大麻素合酶多肽 |
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| KR20180096274A (ko) | 2017-02-21 | 2018-08-29 | 재단법인 금산국제인삼약초연구소 | 인삼 농축액을 포함하는 간질환 개선용 조성물 |
| WO2019053591A1 (en) * | 2017-09-13 | 2019-03-21 | Novartis Ag | USE OF IL-1B BINDING ANTIBODIES FOR THE TREATMENT OF ALCOHOLIC HEPATITIS |
| KR102091528B1 (ko) | 2018-12-21 | 2020-03-24 | 재단법인 금산국제인삼약초연구소 | 인삼 농축액을 포함하는 간질환 개선용 조성물 |
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Also Published As
| Publication number | Publication date |
|---|---|
| EP3064209A1 (en) | 2016-09-07 |
| EP3064209B1 (en) | 2019-11-06 |
| KR20160107420A (ko) | 2016-09-19 |
| KR101695848B1 (ko) | 2017-01-13 |
| US20160256477A1 (en) | 2016-09-08 |
| JP6218870B2 (ja) | 2017-10-25 |
| US20210008088A1 (en) | 2021-01-14 |
| CN105935364B (zh) | 2020-02-11 |
| JP2016166185A (ja) | 2016-09-15 |
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