CN107073024A - 含人参皂苷F1或Rg3作为有效成分的用于预防或治疗格列卫耐药性白血病的药学组合物 - Google Patents
含人参皂苷F1或Rg3作为有效成分的用于预防或治疗格列卫耐药性白血病的药学组合物 Download PDFInfo
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Abstract
本发明涉及一种包含对格列卫耐药性白血病呈现出预防或治疗效果的人参皂苷F1或Rg3作为有效成分的用于预防或治疗格列卫耐药性白血病的药学组合物、包括给药所述药学组合物的步骤的治疗格列卫耐药性白血病的方法以及用于预防或改善格列卫耐药性白血病的食品组合物。由于在利用本发明的药学组合物的情况下，能够有效地治疗对现有的格列卫表现出耐药性的白血病，因此该药学组合物能够被广泛地应用到白血病的有效治疗中。
Description
技术领域
本发明涉及一种包含人参皂苷F1或Rg3作为有效成分的用于预防或治疗格列卫耐药性白血病的药学组合物，更详细而言，本发明涉及一种包含对格列卫耐药性白血病呈现出预防或治疗效果的人参皂苷F1、Rg3或它们的药学上可接受的盐作为有效成分的用于预防或治疗格列卫耐药性白血病的药学组合物、包括给药所述药学组合物的步骤的治疗格列卫耐药性白血病的方法以及用于预防或改善格列卫耐药性白血病的食品组合物。
背景技术
在癌症治疗中主要使用的方法具有外科手术、抗癌化学疗法或放射线疗法等。其中，手术和放射线治疗为仅对切除部位或照射部位有效的局部疗法，抗癌剂治疗疗法为对全身呈现出效果的全身疗法。大部分癌症为从局部开始发病并向全身转移的疾病，由于除早期发现的情况之外已经存在微细的全身转移，因此尽管进行有效的局部疗法也复发的情况较多，从而在大部分癌症治疗中不仅使用局部疗法，而且同时使用对全身扩散的癌症更有效的抗癌剂治疗疗法。对于癌症治疗疗法而言，给药抗癌剂为在通过外科手术去除癌症部位之后，去除肉眼难以观察的非常小的癌组织或从原发性部位转移到其它组织的癌细胞的重要治疗方法。但是，在按肿瘤类型对特定的抗癌剂具有耐药性或长期给药特定抗癌剂时，可能发生因癌细胞获得耐药性而无法正常收获抗癌效果的情况。
慢性骨髓性白血病(Chronic myeloid leukemia，CML)为以骨髓中的骨髓细胞克隆制造的增加和非调节为特征的恶性骨髓肿瘤。根据国际癌症研究所的有关报告，CML(慢性髓细胞白血病)通过第9号染色体的c-abl原癌基因向第22号染色体的Bcr基因的第二外显子的新的下游位置移动而形成费城染色体(Ph：Philadelphia chromosome)并从该费城染色体表达作为嵌合蛋白的Bcr-Abl融合蛋白，所述表达出的融合蛋白导致一系列不相容的造血细胞增值，从而引起白血病的发病。作为这种CML的最有效的治疗剂，已知有格列卫(gleevec)，但已知所述格列卫通过在ATP-结合位点上的竞争阻碍来发挥作用，抑制表达Bcr-Abl的细胞生长或诱导细胞自灭，从而呈现出治疗CML的效果。但是，随着出现多数CML患者对所述格列卫表现出耐药性的有关报告(美国公开专利第2003-0158105号)，要求开发出能够治疗对所述格列卫表现出耐药性的CML的新的抗癌剂，并且正在积极进行对此的研究。
例如，国际公开专利第2008-078203号中公开了包含槟榔胡椒叶提取物的用于治疗格列卫-耐药性白血病的药学组合物，韩国公开专利第2011-0055833号中公开了包含3-羟基黄酮作为有效成分的用于治疗格列卫耐药性白血病的药学组合物，在韩国公开专利第2014-0127985号中公开了包含白桦树树皮提取物的用于治疗格列卫耐药性白血病的药学组合物。这些药学组合物具有大体上来源于天然物而使副作用最小化，并且呈现出治疗格列卫耐药性白血病的效果的优点，但具有因对所述格列卫耐药性白血病的治疗效果较差而需要长期给药的缺点。因此，要求开发出能够使副作用最小化的同时，对格列卫耐药性白血病呈现出优异的治疗效果的治疗剂。
发明内容
技术问题
本发明人为了开发出能够使副作用最小化的同时对格列卫耐药性白血病表现出优异的治疗效果的治疗剂而努力进行了深入的研究，其结果确认到作为人参皂苷的一种的F1或Rg3使副作用最小化的同时，对格列卫耐药性白血病呈现出优异的治疗效果，进而完成了本发明。
技术方案
本发明的一目的在于，提供一种包含作为人参皂苷的一种的F1、Rg3或它们的药学上可接受的盐的用于预防或治疗格列卫耐药性白血病的药学组合物。
本发明的另一目的在于，提供一种包括给药所述药学组合物的步骤的治疗格列卫耐药性白血病的方法。
本发明的又一目的在于，提供一种包含作为人参皂苷的一种F1或Rg3的用于预防或改善格列卫耐药性白血病的食品组合物。
发明的效果
由于在利用本发明的药学组合物的情况下，能够有效地治疗对现有的格列卫表现出耐药性的白血病，因此可以被广泛地应用于白血病的有效治疗中。
附图说明
图1是表示发掘在处理PBMC(外周血单个核细胞)中的NK(自然杀伤)细胞时使CD107a的水平提高的人参皂苷的结果的图表以及表示流式细胞分析结果的图表。
图2是表示IFN-γ(γ-干扰素)在用七种人参皂苷处理后的表达水平变化的图表。
图3是通过使作为格列卫耐药性白血病细胞的KCL-22细胞变异株与NK细胞反应而表示人参皂苷对CD107a表达水平提高所起到的效果的图表。
图4a是表示NK细胞的CD107a表达水平根据人参皂苷F1的处理浓度而变化的图表。
图4b是表示NK细胞的CD107a表达水平根据人参皂苷Rg3的处理浓度而变化的图表。
图5a是表示用人参皂苷F1处理的NK细胞对KCL-22细胞变异株的细胞杀伤活性的图表。
图5b是表示用人参皂苷Rg3处理的NK细胞对KCL-22细胞变异株的细胞杀伤活性的图表。
具体实施方式
在为了开发出能够使副作用最小化的同时，对格列卫耐药性白血病呈现出优异的治疗效果的治疗剂而进行多种研究的过程中，本发明人注意到自然杀伤细胞(naturalkiller cell，NK cell)。已知所述NK细胞以癌症及病毒感染疾病为中心对多种人体疾病的发病发挥中枢作用，已知所述NK细胞与其它免疫细胞不同，能够即时感知癌细胞及病毒感染细胞而将它们直接去除，并且通过表达如IFN-γ的免疫活性因子来调节免疫反应，不仅抑制癌细胞的产生、增值及转移，而且具有去除对表现出抗癌剂耐药性的癌症及癌症的复发很重要的癌干细胞的效果。在若提高这种NK细胞的细胞杀伤活性，则所述NK细胞可分解能够诱发格列卫耐药性白血病的血液内非正常的血细胞的假设下，检索了能提高所述NK细胞的活性的成分的结果，注意到人参皂苷。不仅已知作为从人参中提取到的成分的人参皂苷的稳定性，而且已作出关于其药理活性的多种研究，并已知有些人参皂苷对各种癌症表现出优异的抗癌活性，因此进行了从所述人参皂苷中导出对格列卫耐药性白血病表现出治疗效果的成分的研究。其结果，确认到有些人参皂苷通过提高活体内NK细胞的细胞杀伤活性以使诱发格列卫耐药性白血病的经变异的血细胞分解，从而表现出对格列卫耐药性白血病的抗癌活性。特别是，确认到在用作为属于原人参萜二醇(protopanaxadiol，PPD)的人参皂苷的一种的Rg3和属于原人参萜三醇(protopanaxatriol，PPT)的人参皂苷的一种的F1处理诱发格列卫耐药性白血病的癌细胞并对它们添加NK细胞的情况下，有效地去除诱发格列卫耐药性白血病的经变异的血细胞，从而对格列卫耐药性白血病表现出优异的抗癌活性。
如上述，人参皂苷F1或Rg3可用作格列卫耐药性白血病治疗剂的有效成分，目前为止这种人参皂苷F1或Rg3对格列卫耐药性白血病的治疗效果全然不知，由本发明人首次弄清了该治疗效果。
因此，其优点在于，在对发生白血病的个体给药本发明所提供的药学组合物的情况下，人参草甘F1或Rg3并不是直接作用于诱发格列卫耐药性白血病的经变异的血细胞，而是利用通过增强NK细胞的细胞杀伤活性而使所述经变异的血细胞分解的间接方法来表现出抗癌活性，因此对表现出格列卫耐药性的白血病患者呈现出优异的治疗效果。由于具有这种优点，也可以对患有格列卫耐药性白血病的个体单独给药本发明所提供的药学组合物，还可以与对白血病呈现出治疗效果的其它治疗剂(例如，伊马替尼、尼罗替尼、雷多替尼、依鲁替尼等)一同联合给药本发明所提供的药学组合物。
为了实现上述目的，本发明的一实施方式提供一种包含作为人参皂苷的一种的F1、Rg3或它们的药学上可接受的盐的用于预防或治疗格列卫耐药性白血病的药学组合物。
本发明中的术语“人参皂苷F1(ginsenoside F1)”也称作20-O-β-D-吡喃葡糖基-20(S)-原人参三醇，是指具有下述化学式1的结构的PPT类人参皂苷化合物的一种。已知从抑制癌细胞增值、抗癌剂的抗癌活性增强作用、抑制过敏及由紫外线B的照射导致的细胞凋亡(apoptosis)方面来看，所述人参皂苷F1能保护人类HaCaT(人永生化表皮细胞)角质细胞。但是，关于提高自然杀伤细胞的细胞杀伤活性的效果尚未公知。
[化学式1]
本发明中的术语“人参皂苷Rg3(ginsenoside Rg3)”也称作20(S)-原人参二醇-3-0-β-D-吡喃葡糖基(1，2)-β-D-吡喃葡糖苷，是指具有下述化学式2的结构的PPD类人参皂苷化合物的一种。已知所述人参皂苷Rg3在多种人参皂苷中也表现出特别优异的抗癌活性。此外，所述人参皂苷Rg3不仅表现出这种抗癌活性，而且还表现出神经保护活性、血小板凝集抑制活性、抗氧化活性、抗炎症活性、肾脏保护活性等多种药理活性。但是，关于提高自然杀伤细胞的细胞杀伤活性的效果尚未公知。
[化学式2]
本发明的术语“药学上可接受的盐”是指在作为阳离子和阴离子因静电引力而结合的物质的盐中能够在药剂学上使用的形式的盐，通常可以是金属盐、有机碱盐、无机酸盐、有机酸盐、碱性或酸性氨基酸盐等。例如，作为金属盐可以是碱金属盐(钠盐、钾盐等)、碱土金属盐(钙盐、镁盐、钡盐等)、铝盐等；作为有机碱盐可以是三乙胺盐、吡啶盐、甲基吡啶盐、2,6-二甲基吡啶盐、乙醇胺盐、二乙醇胺盐、三乙醇胺盐、环己胺盐、二环己胺盐、N,N-二苯基乙二胺盐等；作为无机酸盐可以是盐酸盐、氢溴酸盐、硝酸盐、硫酸盐、磷酸盐等；作为有机酸盐可以是甲酸盐、乙酸盐、三氟乙酸盐、酞酸盐、延胡索酸盐、草酸盐、酒石酸盐、顺丁烯二酸盐、柠檬酸盐、琥珀酸盐、甲磺酸盐、苯磺酸盐、p-甲苯磺酸盐等；作为碱性氨基酸盐可以是精氨酸盐、赖氨酸盐、鸟氨酸盐等；作为酸性氨基酸盐可以是天冬氨酸盐、谷氨酸盐等。
特别是，当在化合物内具有酸性官能团时，作为优选的盐，可以是诸如碱金属盐(例如钠盐、钾盐等)、碱土金属盐(例如钙盐、镁盐、钡盐等)等的无机盐以及诸如铵盐的有机盐，当在化合物内具有碱性官能团时，作为优选的盐，可以是如盐酸、氢溴酸盐、硝酸盐、硫酸盐、磷酸盐等的无机酸盐以及诸如乙酸盐、酞酸盐、延胡索酸盐、草酸盐、酒石酸盐、顺丁烯二酸盐、柠檬酸盐、琥珀酸盐、甲磺酸盐、p-甲苯磺酸盐等的有机酸盐。
本发明中的术语“白血病(leukemia)”是指白血球以肿瘤性增值的疾病。所述白血病的种类根据白血病起源的白血球可分为骨髓性白血病和淋巴性白血病，根据进展速度可分为急性白血病和慢性白血病。已知所述白血病的临床状态根据疾病的类型和被侵犯的细胞性质呈现出多种状态，例如淋巴性白血病因淋巴血液细胞变异而发病，骨髓性白血病因骨髓血液细胞变异而发病，慢性骨髓性白血病因处于成熟期的骨髓细胞变异而发病，急性骨髓性白血病因在早期阶段的造血过程中开始分化的骨髓母细胞变异而发病。
应解释为，在本发明中所述白血病是指格列卫耐药性白血病，所述格列卫耐药性白血病可通过给药本发明所提供的药学组合物来治疗。
本发明中的术语“格列卫耐药性白血病”是指对作为慢性骨髓性白血病(Chronicmyeloid leukemia，CML)的治疗剂来开发的格列卫表现出治疗耐药性的白血病。
如上述，由于本发明所提供的用于预防或治疗格列卫耐药性白血病的药学组合物包含人参皂苷F1或Rg3，可通过提高活体内的NK细胞的细胞杀伤活性，来使所述细胞杀伤活性得到增强的NK细胞分解诱发格列卫耐药性白血病的经变异的血细胞，因此不仅呈现出对格列卫耐药性白血病的治疗效果，而且能够安全地给药该药学组合物而无副作用。由此，也可以对患有格列卫耐药性白血病的个体单独给药本发明所提供的药学组合物，还可以与对白血病呈现出治疗效果的其它治疗剂(例如，伊马替尼(imatinib)、尼罗替尼(nilotinib)、雷多替尼(radotinib)、依鲁替尼(ibrutinib)等)一同联合给药本发明所提供的药学组合物。
根据本发明的一实施例，确认到从总计15种(C-K、F2、PD、Rb1、Rb2、Rc、Rd、Rg3、Rh2、F1、PPT、Re、Rg1、Rg2和Rh1)的人参皂苷中筛查用于提高血液内的NK细胞的细胞杀伤活性(cytotoxicity)的人参皂苷的结果，发掘了七种人参皂苷(F2、Rb1、Rg3、Rh2、F1、Rg1和Rg2)(图1)，并且从所述七种人参皂苷中筛选了增强免疫活性因子(IFN-γ)的表达的四种人参皂苷(Rg3、Rh2、F1和Rg1)(图2)，在所述四种人参皂苷中两种人参皂苷(F1和Rg3)也激活NK细胞(图3)，并且浓度依赖性地激活NK细胞(图4a及图4b)。因此，验证所述两种人参皂苷对NK细胞的细胞杀伤活性带来的效果的结果，确认到增强了NK细胞对格列卫耐药性白血病细胞的细胞杀伤活性(图5a及图5b)。
本发明的药学组合物可进一步包含通常在药学组合物的制造中所使用的适当的载体、赋形剂或稀释剂，所述载体可包括非自然载体(non-naturally occuring carrier)。具体而言，可根据各个通常的方法，以散剂、颗粒剂、锭剂、胶囊剂、悬浮液、乳液、糖浆、气溶剂等的口服剂型、外用剂、栓剂和灭菌注射溶液的形态剂型化来使用所述药学组合物。在本发明中，作为所述药学组合物中可包含的载体、赋形剂和稀释剂，可列举乳糖、右旋糖、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、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、滑石、硬脂酸镁和矿物油。在进行制剂化时，利用通常所使用的填充剂、増量剂、结合剂、润湿剂、分散剂、表面活性剂等的稀释剂或赋形剂来制造。用于口服给药的固态制剂包括锭剂、丸剂、散剂、颗粒剂、胶囊剂等，这种固态制剂通过混合至少一种的赋形剂例如淀粉、碳酸钙(calcium carbonate)、蔗糖(sucrose)或乳糖(lactose)、明胶等来制造。此外，除单一的赋形剂以外，也可以使用如硬脂酸镁、滑石等的润滑剂。作为用于口服的液体制剂，适合悬浮剂、内用液剂、油剂、糖浆剂等，除普遍使用的单一的稀释剂即水、液体石蜡以外，可包含各种赋形剂例如润湿剂、甜味剂、芳香剂、保存剂等。在用于非口服给药的制剂中包含经灭菌的水溶液、非水性溶剂、悬浮剂、油剂、冷冻干燥制剂、栓剂。作为非水性溶剂、悬浮剂，可使用如丙二醇(propylene glycol)、聚乙二醇、橄榄油的植物性油、如油酸乙酯的能够给药的酯等。作为栓剂基质，可使用半合成椰油酯(witepsol)、聚乙二醇、吐温(tween)61、可可脂、月桂酸甘油酯、甘油明胶等。
根据本发明的一实施例的药学组合物中所包含的所述制剂的含量并不特别限于此，优选以最终组合物的总重量为基准包含0.0001至50重量％的所述制剂，更优选包含0.01至10重量％的所述制剂。
可以按药剂学上有效的量给药上述本发明的药学组合物，本发明中的术语“药剂学上有效的量”是指按能够适用于药学治疗或预防的合理的受益/危险比例足以用于治疗或预防疾病的量，可根据疾病的重症度、药物的活性、患者的年龄、体重、健康、性别、患者对药物的敏感度、所使用的本发明组合物的给药时间、给药路径和排出率、包含与治疗期间所使用的本发明的组合物配合使用的药物或同时使用的要素以及其它医学领域众所周知的要素来确定有效容量水平。本发明的药学组合物可作为个别治疗剂来给药，或者也可以与其它治疗剂联合给药，还可以与现有的治疗剂一同按顺序或同时给药。并且，还可以给药一种或多种药物。考虑上述所有要素并在无副作用的情况下给药能够以最小量获得最大效果的量很重要。
本领域技术人员可通过考虑使用目的、疾病的严重程度、患者的年龄、体重、性别、既往病历或者作为有效成分来使用的物质的种类等，来确定本发明的药学组合物的给药量。例如，可在一天内对包括人类在内的哺乳动物给药10至100mg/kg本发明的药学组合物，更优选地可给药10至30mg/kg本发明的药学组合物，但本发明的组合物的给药频率并不特别限于此，可在一天内给药一次或三次，或者经划分容量而一天给药多次。
为了实现上述目的，本发明的另一实施方式提供包括以下步骤的用于治疗格列卫耐药性白血病的方法：按药剂学上有效的量对患有格列卫耐药性白血病的个体给药所述药学组合物。此时，可以对个体单独给药所述药学组合物，也可以联合给药本发明的药学组合物和其它用于治疗白血病的药学组合物(例如，伊马替尼、尼罗替尼、雷多替尼、依鲁替尼等)。
本发明中的术语“个体”是指包括患有所述格列卫耐药性白血病的人类在内的所有动物。可通过对个体给药本发明的组合物，从而治疗格列卫耐药性白血病。
本发明中的术语“治疗”是指通过给药本发明的药学组合物而使格列卫耐药性白血病好转或产生有益变化的所有行为。
本发明中的术语“给药”是指通过某种适当的方法向对象导入本发明的药学组合物的行为，可通过给药路径即能够到达目的组织的口服或非口服的多种路径来给药本发明的药学组合物。
在本发明的治疗格列卫耐药性白血病的方法中，也可以通过所述药学组合物的给药路径即能够到达目的组织的某种普通的路径来给药所述药学组合物。本发明的药学组合物并不特别限于此，可根据目的进行腹腔内给药、静脉内给药、肌肉内给药、皮下给药、皮内给药、口服给药、鼻腔内给药、肺内给药、直肠内给药。此外，可通过能够使活性物质向标的细胞移动的任意装置来给药所述组合物。
本发明的又一实施方式提供一种包含作为人参皂苷的一种的F1或Rg3的用于预防或改善格列卫耐药性白血病的食品组合物。
由于所述人参皂苷F1或Rg3为来源于自古以来食用或药用的人参的化合物，因此可通过被制造成能够呈现出预防格列卫耐药性白血病的发病或改善患有格列卫耐药性白血病的效果的食品形式来供个体摄取所述人参皂苷F1或Rg3。此时，并不特别限定所述食品中所包含的所述人参皂苷F1或Rg3的含量，相对于食品组合物的总重量可包含0.001至10重量％的所述人参皂苷F1或Rg3，更优选地相对于食品组合物的总重量可包含0.1至1重量％的所述人参皂苷F1或Rg3。在食品为饮料的情况下，可以以100ml为基准按1至10g的比例包含所述人参皂苷F1或Rg3，更优选地可按2至7g的比例包含所述人参皂苷F1或Rg3。此外，所述组合物可包含通常在食品组合物中被使用且能够提高气味、味道、视觉等的附加成分。例如，附加成分可包括维生素A、C、D、E、B1、B2、B6、B12、烟酸(niacin)、生物素(biotin)、叶酸(folate)、泛酸(panthotenic acid)等。此外，附加成分可包括锌(Zn)、铁(Fe)、钙(Ca)、铬(Cr)、镁(Mg)、锰(Mn)、铜(Cu)等的矿物质。此外，附加成分可包括赖氨酸、色氨酸、半胱氨酸、缬氨酸等的氨基酸。此外，在所述组合物中可添加防腐剂(山梨酸钾、苯甲酸钠、水杨酸、脱氢醋酸钠等)、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(焦油色素等)、发色剂(亚硝酸钠、亚醋酸钠等)、漂白剂(亚硫酸钠)、调味剂(MSG谷氨酸单钠等)、甜味剂(甘精、甜蜜素、糖精、钠等)、香料(香兰素、内酯等)、膨胀剂(明矾、D-酒石酸氢钾等)、强化剂、乳化剂、增稠剂(糊料)、被膜剂、胶母糖基础剂、消泡剂、溶剂、改良剂等的食品添加剂(food additives)。根据食品的种类来选择所述添加剂，并以适当的量使用所述添加剂。
另外，可利用包含所述人参皂苷F1或Rg3的用于预防或改善格列卫耐药性白血病的食品组合物，来制造用于预防或改善格列卫耐药性白血病的健康功能性食品。
作为具体例，可利用所述食品组合物来制造能预防或改善格列卫耐药性白血病的加工食品，例如所述食品组合物可被制造成作为糕点、饮料、酒类、发酵食品、罐头、牛奶加工食品、肉类加工食品或面条加工食品形式的健康功能性食品。此时，糕点包括饼干、派、蛋糕、面包、糖果、果冻、口香糖、麦片(包括谷物片等的代餐类产品)等。饮料包括饮用水、碳酸饮料、功能性离子饮料、果汁(苹果汁、梨汁、葡萄汁、芦荟汁、柑橘汁、桃汁、胡萝卜汁、西红柿汁等)、酒酿等。酒类包括清酒、威士忌、烧酒、啤酒、洋酒、果酒等。发酵食品包括酱油、大酱、辣椒酱等。罐头包括水产品罐头(例如，金枪鱼罐头、鲭鱼罐头、秋刀鱼罐头或海螺罐头等)、畜产品罐头(牛肉罐头、猪肉罐头、鸡肉罐头或火鸡罐头等)、农产品罐头(玉米罐头、桃罐头或菠萝罐头等)。牛奶加工食品包括奶酪、黄油、酸奶等。肉类加工食品包括炸猪排、炸牛排、炸鸡排、香肠、糖醋肉、鸡块类、宫廷烤牛肉等。面条加工食品包括密封包装生面等的面条。除此之外，还可以在袋装食品、汤类等中使用所述组合物。
本发明中的术语“健康功能性食品(functional food)”为与特定保健用食品(food for special health use，FoSHU)相同的术语，是指被加工为除供给营养以外还有效地呈现出活体调节功能的医学、医疗效果较高的食品，为了获取对白血病的预防或改善有用的效果，可以以锭剂、胶囊、粉末、果颗粒、液相、丸等的多种形式制造所述食品。
实施例
下面，通过实施例对本发明进行更详细说明。但是，这些实施例用于示意性地说明本发明，本发明的范围并不限定于这些实施例。
实施例1：发掘提高NK细胞的细胞杀伤活性的人参皂苷
为了发掘对NK细胞的细胞杀伤活性带来影响的人参皂苷，用15种(C-K、F2、PPD、Rb1、Rb2、Rc、Rd、Rg3、Rh2、F1、PPT、Re、Rg1、Rg2和Rh1)人参皂苷处理PBMC(peripheralblood mononuclear cell，外周血单核细胞)，并通过流式细胞分析来测定作为呈现出由NK细胞表达的细胞杀伤效果的标记蛋白质的CD107a的水平(图1)。
此时，使用以如下方式筛选的所述PBMC。即，将抽出的血液装入到单个核细胞制备管(Vacutainer Cell Preparation Tube)(sodium heparin(肝素钠)；BD Biosciences(BD生物技术))中并进行离心分离而回收血沉棕黄层(buffy coat；lymphocytes andmonocyte band(淋巴细胞和单核细胞带))，并且利用PBS(磷酸盐缓冲液)清洗经回收的血沉棕黄层之后，将其施加到人类NK细胞阴性选择试剂盒(human NK cell negativeselection kit)(Miltenyl Biotech(美天旎生物技术))中来分离出PBMC。将所述分离出的PBMC应用到使用抗-CD3抗体、抗-CD16抗体及抗-CD56抗体的流式细胞分析中，并在之后的实施例中使用所述PBMC中所包含的NK细胞的纯度为95％以上的试样。
此外，以如下方式测定所述CD107a的水平。即，用所述各个人参皂苷处理所述NK细胞的纯度为95％以上的PBMC试样，并且通过处理标的细胞(K562细胞)来刺激NK细胞。接着，通过进行利用抗-CD3抗体及抗-CD56抗体的流式细胞分析而分离出NK细胞，并且使用抗-CD107a抗体对NK细胞进行免疫染色之后，测量CD107a的水平。
图1是表示发掘在处理PBMC中的NK细胞时使CD107a的水平提高的人参皂苷的结果的图表以及表示流式细胞分析结果的图表。如图1所示，确认到七种人参皂苷(F2、Rb1、Rg3、Rh2、F1、Rg1和Rg2)能够使由NK细胞表达的CD107a的水平提高。
实施例2：筛选出提高NK细胞的免疫活性因子(IFN-γ)表达的人参皂苷
用上述实施例1中发掘到的七种人参皂苷进行处理，并筛选出使NK细胞的免疫活性因子(IFN-γ)表达水平提高的人参皂苷(图2)。此时，以如下方式测定IFN-γ表达水平。即，用所述各个人参皂苷处理由上述实施例1分离出的PBMC，并且对细胞数相同的标的细胞(KCL-22细胞变异株)进行处理以刺激之后，用布雷非德菌素A(Brefeldin A)(GolgiPlug；BD Biosciences)进行处理。接着，通过进行利用抗-CD3抗体及抗-CD56抗体的流式细胞分析而分离来源于PBMC的NK细胞，并用Cytofix/Cytoperm(BD Biosicences)处理所述分离出的NK细胞后进行穿孔，然后用抗-IFN-γ抗体进行免疫染色以测定IFN-γ的水平(图2)。
图2是表示IFN-γ在用所述七种人参皂苷处理后的表达水平变化的图表。如图2所示，确认到当用所述七种人参皂苷中的四种人参皂苷(Rg3、Rh2、F1和Rg1)进行处理时，IFN-γ的表达水平提高。
实施例3：筛选出提高非激活的NK细胞中的CD107a水平的人参皂苷
从由上述实施例2筛选出的四种人参皂苷(Rg3、Rh2、F1和Rg1)中，筛选出诱导非激活的NK细胞中的CD107a水平提高的人参皂苷。
具体而言，在用所述四种人参皂苷处理从PBMC分离出的NK细胞以激活该NK细胞，并添加作为格列卫耐药性白血病细胞的KCL-22细胞变异株之后，测定并比较CD107a的水平(图3)。此时，作为对照组，使用由DMSO(二甲亚砜)代替人参皂苷来进行处理后的NK细胞。
图3是通过使作为格列卫耐药性白血病细胞的KCL-22细胞变异株与NK细胞反应而表示人参皂苷对CD107a表达水平提高所起到的效果的图表。如图3所示，确认到在使作为格列卫耐药性白血病细胞的KCL-22细胞变异株与NK细胞反应时，CD107a的水平显著提高，在所有实验条件下，当在人参皂苷中采用F1进行处理时，显示出最高水平的CD107a，当在人参皂苷中采用Rg3进行处理时，显示出次高水平的CD107a。
实施例4：人参皂苷F1或Rg3在不同浓度下对NK细胞中的CD107a水平提高起到的效
果
通过用由上述实施例3筛选出的将CD107a的水平提高至最高水平的F1和将CD107a的水平提高至次高水平的Rg3分别以不同浓度(5至20μM)处理从PBMC分离出的NK细胞，并测定取决于处理浓度的CD107a水平的变化(图4a及图4b)。此时，作为对照组，使用由DMSO代替人参皂苷来进行处理后的NK细胞。
图4a是表示NK细胞的CD107a表达水平根据人参皂苷F1的处理浓度而变化的图表，图4b是表示NK细胞的CD107a表达水平根据人参皂苷Rg3的处理浓度而变化的图表。如图4a及图4b所示，确认到人参皂苷F1和Rg3均浓度依赖性地使CD107a在NK细胞中的表达水平提高。
因此，人参皂苷F1或Rg3被分析为呈现出促进NK细胞对格列卫耐药性白血病的细胞杀伤活性的效果。
实施例5：用人参皂苷F1或Rg3处理的NK细胞的细胞杀伤活性
在用所述人参皂苷F1或Rg3处理从上述实施例1分离出的PBMC，并且通过按多种E:T比率(PBMC的细胞数和标的细胞的细胞数之比率＝0.625:1、1.25:1、2.5:1或5:1)添加用铕(europium)荧光染料标记后的标的细胞(KCL-22细胞变异株)后使其反应，从而利用由所述人参皂苷激活的NK细胞来分解所述标的细胞并将被标记至标的细胞的铕(europium)荧光染料释放至反应液中。在结束反应之后，通过测定所述反应液中所包含的铕(europium)荧光染料的水平，来比较NK细胞的细胞杀伤活性(图5a及图5b)。此时，作为对照组，使用由DMSO代替人数皂苷来进行处理后的NK细胞。
图5a表示用人参皂苷F1处理的NK细胞对KCL22-细胞变异株的细胞杀伤活性，图5b表示用人参皂苷Rg3处理的NK细胞对KCL-22细胞变异株的细胞杀伤活性。如图5a及图5b所示，确认到人参皂苷F1或Rg3能促进NK细胞对KCL-22细胞变异株的细胞杀伤活性。
综上，可知人参皂苷F1或Rg3能够通过激活NK细胞，来增强对格列卫耐药性白血病细胞的细胞杀伤活性。
因此，可知所述人参皂苷F1或Rg3可用作为用于预防或治疗格列卫耐药性白血病的药学组合物的有效成分。
Claims (7)
1.一种用于预防或治疗格列卫耐药性白血病的药学组合物，所述药学组合物包含人参皂苷F1、人参皂苷Rg3或它们的药学上可接受的盐。
2.根据权利要求1所述的药学组合物，其中，
所述人参皂苷F1或所述人参皂苷Rg3增强自然杀伤细胞的自然杀伤活性。
3.根据权利要求1所述的药学组合物，其中，
所述药学组合物进一步包含白血病治疗剂。
4.根据权利要求3所述的药学组合物，其中，
所述白血病治疗剂选自由伊马替尼、尼罗替尼、雷多替尼、依鲁替尼和它们的组合构成的组。
5.根据权利要求1所述的药学组合物，其中，
所述药学组合物进一步包含药学上可接受的载体、赋形剂或稀释剂。
6.一种治疗格列卫耐药性白血病的方法，包括以下步骤：
按药剂学上有效的量对患有格列卫耐药性白血病的个体给药权利要求1至5中的任一项所述的药学组合物。
7.一种用于预防或改善格列卫耐药性白血病的食品组合物，包含人参皂苷F1、人参皂苷Rg3或它们的药学上可接受的盐。
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| PCT/KR2016/004699 WO2016178510A2 (ko) | 2015-05-06 | 2016-05-04 | 진세노사이드 Ｆ1 또는 Ｒｇ3를 유효성분으로 포함하는 글리벡 내성 백혈병 예방 또는 치료용 약학 조성물 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107519189A (zh) * | 2016-06-22 | 2017-12-29 | 智能合成生物中心 | 包含人参皂苷f1作为有效成分的免疫增强用组合物 |
| CN108904809A (zh) * | 2018-08-20 | 2018-11-30 | 黎庆有 | 一种靶向抗肿瘤药物 |
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| KR101948534B1 (ko) * | 2017-04-20 | 2019-02-15 | 주식회사 이뮤니스바이오 | 세포밀도 조절을 이용한 자연살해세포의 대량증식방법 |
| JP7491742B2 (ja) | 2020-05-29 | 2024-05-28 | 大木製▲薬▼株式会社 | 耐性阻害剤、耐性阻害用飲食品組成物、耐性阻害方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004056379A1 (en) * | 2002-12-23 | 2004-07-08 | Panagin Pharmaceuticals Inc. | Saponins and sapogenins for use in combination therapy for cancer |
| CN102068477A (zh) * | 2010-12-31 | 2011-05-25 | 浙江省中医院 | 人参有效部位及其制备方法和应用 |
| CN103570790A (zh) * | 2012-08-07 | 2014-02-12 | 中国科学院上海药物研究所 | 原人参二醇衍生物及其制备方法、包含该衍生物的组合物及其用途 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60232370D1 (de) | 2001-06-14 | 2009-06-25 | Univ California | Mutationen in der mit der resistenz gegenüber sti- |
| BR0311866A (pt) * | 2002-06-11 | 2005-03-15 | Panagin Pharmaceuticals Inc | Composições de saponinas ou sapogeninas para terapia de câncer |
| CA2673264A1 (en) | 2006-12-21 | 2008-07-03 | Piramal Life Sciences Limited | Herbal composition and process for its preparation |
| MX2009013069A (es) * | 2007-06-01 | 2010-03-17 | Wyeth Llc | Tratamiento de leucemia resistente al imatinib. |
| KR20110055833A (ko) | 2009-11-20 | 2011-05-26 | 건국대학교 산학협력단 | 플라보노이드를 유효성분으로 하는 백혈병 치료용 조성물 |
| KR101483055B1 (ko) | 2013-04-26 | 2015-01-15 | 초당약품공업 주식회사 | 백합나무 수피에서 만성 골수성 백혈병 치료 성분을 추출 분리하는 방법 |
-
2015
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-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004056379A1 (en) * | 2002-12-23 | 2004-07-08 | Panagin Pharmaceuticals Inc. | Saponins and sapogenins for use in combination therapy for cancer |
| CN102068477A (zh) * | 2010-12-31 | 2011-05-25 | 浙江省中医院 | 人参有效部位及其制备方法和应用 |
| CN103570790A (zh) * | 2012-08-07 | 2014-02-12 | 中国科学院上海药物研究所 | 原人参二醇衍生物及其制备方法、包含该衍生物的组合物及其用途 |
Non-Patent Citations (4)
| Title |
|---|
| NGUYEN HUU TUNG等: "Dammarane-type saponins from the flower buds of Panax ginseng and their effects on human leukemia cells", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
| SEUNG-WHAN KIM等: "Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg3", 《BIOCHEMICAL PHARMACOLOGY》 * |
| XING-XIANG PENG等: "Overexpression of P-glycoprotein induces acquired resistance to imatinib in chronic myelogenous leukemia cells", 《CHINESE JOURNAL OF CANCER》 * |
| 王英 等: "人参皂苷Rg3对NK 细胞与K562 细胞的结合率及毒性作用影响的实验研究", 《中药材》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107519189A (zh) * | 2016-06-22 | 2017-12-29 | 智能合成生物中心 | 包含人参皂苷f1作为有效成分的免疫增强用组合物 |
| CN108904809A (zh) * | 2018-08-20 | 2018-11-30 | 黎庆有 | 一种靶向抗肿瘤药物 |
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| EP3181137A4 (en) | 2018-02-28 |
| CN107073024B (zh) | 2020-03-17 |
| KR20160132194A (ko) | 2016-11-17 |
| JP2019031527A (ja) | 2019-02-28 |
| WO2016178510A3 (ko) | 2016-12-29 |
| CA2961744A1 (en) | 2016-11-10 |
| JP2017529350A (ja) | 2017-10-05 |
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| WO2016178510A2 (ko) | 2016-11-10 |
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