CN112245443A - 人参皂苷Rg3与Rg5的组合物及其抗肿瘤等药用 - Google Patents
人参皂苷Rg3与Rg5的组合物及其抗肿瘤等药用 Download PDFInfo
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- CN112245443A CN112245443A CN202010861400.7A CN202010861400A CN112245443A CN 112245443 A CN112245443 A CN 112245443A CN 202010861400 A CN202010861400 A CN 202010861400A CN 112245443 A CN112245443 A CN 112245443A
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Abstract
本发明公开了一种人参皂苷Rg3与人参皂苷Rg5的组合物及其制备方法，以及在提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳、抗抑郁的药品和食品、保健品中的应用。该组合物见效快、毒副作用小，可长期服用，是一种安全、高效、稳定、制备工艺简单的药物和保健食品，适于工业化生产，易于推广。本发明为提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳、抗抑郁的药品和食品提供了一种新的原料与生产工艺。
Description
技术领域
本发明属于药物化学领域，具体而言，本发明涉及一种人参皂苷Rg3与人参皂苷Rg5的组合物的制备方法，及其在提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳、抗抑郁的药品、食品和保健品中的应用。
背景技术
人参是属于五加科人参属的植物，在中国，韩国，日本被广泛应用，已有2000多年历史，以预防疾病和延长寿命为主要使用目的。据《神农本草经》记载，人参有：‘补五脏，安神经，定魂魄，止惊悸，除邪气，名目益智，久服轻身延年’的作用。现代医学研究表明人参的主要功效和作用有：对于神经中枢系统的作用，抗癌抗肿瘤作用，免疫功能调节作用，抗糖尿病的作用，增强肝功能作用，心脑血管障碍改善，抗动脉硬化作用，血压调节作用，以及更年期障碍和抗骨质疏松作用，抗疲劳，抗氧化，抑制衰老等。
人参皂苷作为人参的主要有效成分，被广泛研究和使用，其中人参皂苷Rg3与人参皂苷Rg5最为引人瞩目，其作为人参的主要有效成分，安全性良好，已经被制成抗肿瘤口服制剂应用于临床，作为注射剂被深入研究。
然而，本发明人发现，现有技术要么以提纯的一种或几种人参皂苷为研究对象，进行药理作用研究，其中人参皂苷Rg3与人参皂苷Rg5的用量往往比较接近，要么以包括大量不同种类中药材(其中包括人参)的混合物或提取物为研究对象，其中通常不鉴定人参皂苷Rg3与人参皂苷Rg5的含量。本发明人依赖于长期的传统中医药和现代医药的研究经验，令人意外地开发出了一种人参皂苷Rg3与人参皂苷Rg5的组合物的制备方法，其不但简单、工艺条件温和，而且适用配方广泛，获得了大量有效的人参皂苷Rg3与人参皂苷Rg5的组合物，可广泛应用于提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳和抗抑郁等，在药物制剂、食品及保健品等领域具有广阔的应用前景。
发明内容
本发明的人参皂苷Rg3与人参皂苷Rg5的组合物在提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳、抗抑郁方面功效强，为研制此类疾病的新药提供了新的途径，即在治疗、调理和缓解此类疾病的药物、食品或保健品中的新应用提供了新的思路。
为实现上述目的，本发明提供一种人参皂苷Rg3与人参皂苷Rg5的组合物、制备方法，及其应用。
特别是，所述人参皂苷Rg3，是由s构型人参皂苷Rg3，或者是r构型人参皂苷Rg3，或者两种构型的人参皂苷Rg3按任意比例混合组成。
特别是，所述人参皂苷Rg3与人参皂苷Rg5的组合物中，人参皂苷Rg3与人参皂苷Rg5的重量份配比为1～99:1～99。
特别是，所述人参皂苷Rg3与人参皂苷Rg5的组合物，是由人参与其他中药材经过特定工艺制备而成的混合物，人参皂苷Rg3与人参皂苷Rg5的重量在中药组分混合物中的占比为1％-100％。
尤其是，所述人参皂苷Rg3与人参皂苷Rg5的组合物，还包括人参与其他中药材经过特定工艺制备而成的混合物与药学上可接受的载体，经过物理、化学方法处理形成的复合物。
特别是，药学上可接受的载体，包括但不限于α-、β-或γ-环糊精或其衍生物，中药组分混合物与载体的重量之比为1:1～1:100，优选为1:10，进一步优选为1:5，更进一步优选为1:2，再更进一步优选为1:1。
特别是，药学上可接受的载体通常被保健专家认可用于这一目的且作为药剂的非活性成分。有关药学上可接受的载体的汇编可以在《药物赋形剂手册》(Handbook ofPharmaceutical excipients，第2版，由A.Wade和P.J.Weller编辑；American Phar-maceutical Association出版，Washington and The Pharmaceutical Press,London,1994)等工具书中找到。食品添加剂是有意识地一般以少量添加于食品，以改善食品的外观、风味、组织结构或贮存性质的非营养物质。有关食品添加剂可在中国食品安全国家标准《食品添加剂使用标准》中找到。食品添加剂是有意识地一般以少量添加于食品，以改善食品的外观、风味、组织结构或贮存性质的非营养物质。有关食品添加剂可在中国食品安全国家标准《食品添加剂使用标准》中找到。
尤其是，所述的载体包括赋形剂，如淀粉、水等；润滑剂，如硬脂酸镁等；崩解剂，如微晶纤维素等；填充剂，如乳糖等；粘结剂，如预胶化淀粉、糊精等；甜味剂；抗氧化剂；防腐剂、矫味剂、着色剂、香料等。
特别是，所述药物以片剂、胶囊剂、丸剂、散剂、颗粒剂、糖浆剂、溶液剂、乳剂、注射剂、喷雾剂、气雾剂、凝胶剂、霜剂、巴布剂、橡胶贴膏剂或贴膏剂形式存在。
特别是，所述食品以乳制品、糖果、饮料、饼干、茶叶及相关制品、酒等食品形式存在。
特别是，所述保健食品以片剂、胶囊剂、丸剂、散剂、颗粒剂、糖浆剂、溶液剂、乳剂、喷雾剂、气雾剂、凝胶剂、霜剂、巴布剂、橡胶贴膏剂或贴膏剂形式存在，或者以乳制品、糖果、饮料、饼干、茶叶及相关制品、酒等食品形式存在。
其中，所述复合物中中药组分与环糊精或环糊精的衍生物的重量之比为1：1-100。
特别是，所述环糊精为α-或β-、γ-环糊精；所述环糊精衍生物为羟乙基β-环糊精、2,6-二甲基β-环糊精、2,3,6-三甲基β-环糊精、2,6-二乙基β-环糊精、2,3,6-三乙基β-环糊精、麦芽糖基β-环糊精或磺丁醚β-环糊精、对甲基苯磺酰氯(p-TsCl)取代的β-环糊精、6-位取代的β-CD对甲基苯磺酸酯(β-环糊精-6-OTs)、2-氧羟丙基-β-环糊精、2-位单取代的对甲基苯磺酸酯(β-环糊精-2-OTs)、β-环糊精对甲基苯磺酸酯(Tosyl-β-CD)、β-环糊精的星形大分子PCL-(Tos)7-β-CD。
更具体地，本发明的第一方面提供了一种人参皂苷Rg3与人参皂苷Rg5的组合物的制备方法，其包括如下步骤：
1)将人参与中药材混合；
2)将步骤1)获得的混合物加水煎煮多次，收集并合并煎煮液；
3)向步骤2)获得的煎煮液加入澄清剂，混匀后静置并过滤；
4)干燥步骤3)获得的滤液，得干燥物；
5)向步骤4)获得的干燥物中加入乙醇，加热溶解，过滤，冷析
6)干燥步骤5)获得的结晶。
其中，所述中药材不是人参。优选地，在本发明的第一方面的方法中，所述中药材选自由桑葚、炒枳壳、白芍、佛手、藕节、炒枳实、白果、柿蒂、草乌叶、莲房、椿皮、侧柏叶、石榴皮、山茱萸、五倍子、白及、白附子、川楝子、天花粉、党参、紫鸢、青蒿、皂刺、小茴、地肤子、桃仁、乌梅、仙灵脾、鸡内金、生地、山药、秦艽、沙参、石韦、丹参、牵牛子、胡芦巴、扁豆、苏子、清半夏、黄连、补骨脂、黄柏、元胡、青果、墨旱莲、木瓜、马齿苋、香橼、牛膝、覆盆子、何首乌、秦皮、棕榈、莲子、仙鹤草、青梅、白帆、罂粟壳、诃子、金樱子、地榆、杏仁、青皮、栀子、女贞子、熟地、黄芩、芦根、黄芪、莪术、桑白皮、麦冬、槟榔、生乳香、鸡血藤、白术、地骨皮、当归、乌梅、麦芽、枇杷叶、柏子仁、桂皮、天冬、生没药、桔梗、茅根、制附子、菊花、木香、百步、三棱、杜仲、陈皮、大黄、大腹皮、天麻、太子参、赤芍、旋复花、夏枯草、菟丝子、骨碎补、郁金、南星、蒲公英、甘草、升麻、地丁、茜草、乌药、五加皮、川乌、荔枝壳、余甘子、射干、大青叶、吴茱萸、红花、香附、五味子、酸枣仁、山楂和紫草组成的组中的一种获得多种。
更优选地，所述中药材选自由郁金、南星、百部、菊花、木香、五味子、三棱、白术、余甘子、牵牛子、黄柏、补骨脂、扁豆、乌梅、苏子、丹参、石韦、山药、生地、秦艽、沙参、黄连、葫芦巴、元胡、青梅、杜仲、陈皮、酸枣仁、白果、石榴皮、桃仁、白芨、菟丝子、山楂、白芍、侧柏叶、太子参、赤芍、小茴香、青蒿、五倍子、天花粉、党参、川楝子、山茱萸、枳实、莲房、桑葚、鸡内金、枳壳、椿皮、草乌、紫苑、皂刺、地肤子、半夏、大黄、天麻、旋复花和夏枯草组成的组中的一种或者多种。
优选地，在本发明的第一方面的方法中，人参与中药材的重量比为1:100至100:1，例如为1：90～100、1：45～55、10：8～12、45～55：1或90～100：1，优选为1：100、1：50、10：10、50：1或100：1。
优选地，在本发明的第一方面的方法中，煎煮的次数为2～5次，优选为3次。每次煎煮完成时，收集煎煮液，待用，如还需加水煎煮，则将收集掉煎煮液的滤渣再次加水煎煮，直至最后一次加水煎煮完成，合并在前收集的煎煮液。
优选地，在本发明的第一方面的方法中，每次煎煮用的水的重量为人参与中药材的总重量的2-100倍量，优选为2-80倍，更优选为2-50倍。
优选地，在本发明的第一方面的方法中，每次煎煮时间为1-36小时，优选为2-24小时，更优选为5-12小时。
优选地，在本发明的第一方面的方法中，每次煎煮的温度为90～100℃，优选为95～100℃，例如煎煮以保持沸腾状态。煎煮在密闭容器内进行。
优选地，在本发明的第一方面的方法中，每次煎煮的时间为1-36小时，优选为2-24小时，更优选为5-12小时。
优选地，在本发明的第一方面的方法中，澄清剂是药学上和/或食品上可接受的澄清剂，例如天然澄清剂。这样的澄清剂可以从商业渠道购买获得，例如ZTC1+1澄清剂。ZTC1+1澄清剂的加入量为其终浓度为200～800ppm。
优选地，在本发明的第一方面的方法中，静置的时间为4-48小时，优选为4-24小时，更优选为8-12小时。
优选地，在本发明的第一方面的方法中，结晶使用乙醇的水溶液，优选为40-90％(V/V)乙醇溶液，更优选为50-80％(V/V)乙醇溶液。更优选地，乙醇的水溶液的重量是干燥步骤3)获得的滤液而得的干燥物的2-500倍量，进一步优选为10-100倍量。
优选地，在本发明的第一方面的方法中，在步骤6)之后还可以包括检测步骤。例如，通过高效液相方法检测诸如人参皂苷Rg3和/或人参皂苷Rg5的成分含量。
本发明的第二方面提供了一种人参皂苷Rg3与人参皂苷Rg5的组合物，其由本发明的第一方面的方法制备而得。其中，人参皂苷Rg3可以是s型人参皂苷Rg3，也可以是r型人参皂苷Rg3，或者是上述两种构型的混合物。
优选在本发明第二方面的组合物中，人参皂苷Rg3与人参皂苷Rg5的总和重量占该组合物的比例为1％-100％，优选为2～99％。
优选在本发明第二方面的组合物中，人参皂苷Rg3与人参皂苷Rg5的重量比为1:99～99：1。
本发明的第三方面提供了一种复合组合物，其包括本发明第二方面的组合物和药学上或食品上可接受的载体。
优选在本发明第三方面的复合组合物中，本发明第二方面的组合物的重量与药学上或食品上可接受的载体的重量之比为1:1～1:100。
优选本发明第三方面的复合组合物可以是药物组合物，其包括本发明第二方面的组合物和药学上可接受的载体。药学上可接受的载体，包括但不限于α-、β-或γ-环糊精或其衍生物。优选所述药物组合物以片剂、胶囊剂、丸剂、散剂、颗粒剂、糖浆剂、溶液剂、乳剂、注射剂、喷雾剂、气雾剂、凝胶剂、霜剂、巴布剂、橡胶贴膏剂或贴膏剂形式存在。
优选本发明第三方面的复合组合物可以是食品组合物，其可以以乳制品、糖果、饮料、饼干、茶叶及相关制品、酒等食品形式存在。
优选本发明第三方面的复合组合物可以是保健品组合物，其可以以片剂、胶囊剂、丸剂、散剂、颗粒剂、糖浆剂、溶液剂、乳剂、喷雾剂、气雾剂、凝胶剂、霜剂、巴布剂、橡胶贴膏剂或贴膏剂形式存在，或者以乳制品、糖果、饮料、饼干、茶叶及相关制品、酒等食品形式存在。
本发明的第四方面提供了本发明第二方面的组合物在制备提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳或抗抑郁的药品、食品或保健品中的应用。相应地，本发明第五方面提供了一种提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳或抗抑郁的方法，其包括向有需要的个体施用有效量的本发明第二方面的组合物。
其中，优选个体是人，施用于人的有效量可以通过动物实验得出的有效量经等效剂量换算而得。
与现有技术相比，本发明具有如下的明显优点：
本发明人参皂苷Rg3与人参皂苷Rg5的组合物的制备方法简便、适于工业化生产，具有提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳、抗抑郁的明显作用，具有广泛的应用前景。
1、本发明人参皂苷Rg3与人参皂苷Rg5组合物，配方独特，安全性高，质量可控；
2、本发明组合物发掘了新的药用价值，系列试验研究证明其具有提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳、抗抑郁的效果，疗效确切；
3、本发明组合物制备方法简单，工艺条件温和，成本低廉，费用低，而且适用配方广泛；
4、本发明产品原料来源丰富、价廉、临床使用安全，制备工艺简单，可制成各种剂型，且服量小，使用方便，因此易于推广。
具体实施方式
下面通过具体实施方式来进一步描述本发明所述配方的有益效果。这些实施例仅是范例性的，并不对本发明的范围构成任何限制。本领域技术人员应该理解的是，在不偏离本发明的配方思路、用途范围下可以对本发明技术方案的细节和形式进行修改或替换，但这些修改和替换均落入本发明的保护范围内。
实施例1-9人参皂苷Rg3与人参皂苷Rg5的组合物的制备
特定工艺路线为：以水煎煮三次，水液合并，合并浓缩至生药：水为1:5，保持温度为60-80℃，加入ZTC1+1-II型澄清剂(可购自武汉正天成生物科技有限公司)至其终浓度500ppm，搅拌均匀，静置，过滤，滤液收干，加入乙醇溶液于60℃溶解，过滤后降温，用冰水浴析出，收集析出物，烘干即得。经高效液相方法检测各成分含量。
将人参分别与各种生药按表1的重量称量，按照上述工艺路线，以表2的参数进行混合提取，制备。所得成品的检测数据见表3。
表1实施例1-198的原料配比
表2实施例1-198样品制备工艺参数及成品重量
表3实施例1-198的组合物的含量
实施例181-198人参皂苷Rg3与人参皂苷Rg5组合物与环糊精的组合物的制备
取实施例1-198制备的人参皂苷Rg3与人参皂苷Rg5组合物，以表4所述重量比、按以下方法制备组合物：(1)直接加入到环糊精溶液中，或(2)直接加入到环糊精溶液中并充分搅拌1-24h、(3)直接加入到环糊精溶液中并加热10-120分钟、(4)直接加入到环糊精溶液中并超声10-120分钟、(5)直接与环糊精粉末研磨10-120分钟、(6)使人参皂苷Rg3与人参皂苷Rg5组合物与所述环糊精粉末混合均匀、过筛；(7)直接加入环糊精衍生物溶液中，或(8)直接加入到环糊精衍生物溶液中并充分搅拌1-24h、(9)直接加入到环糊精衍生物溶液中并加热10-120分钟、(10)直接加入到环糊精衍生物溶液中并超声10-120分钟、(11)直接与环糊精衍生物粉末研磨10-120分钟、(12)与环糊精衍生物粉末混合均匀、过筛。
表4实施例181-198的原料配比和制备方法
实施例181-198中的辅料以选用β-环糊精为例进行举例说明，其他环糊精、环糊精衍生物均适用于本发明，例如1)β-羟丙基环糊精、2)羟乙基-β-环糊精、3)2,6-二甲基-β-环糊精、4)2,3,6-三甲基-β-环糊精、5)2,6-二乙基-β-环糊精、6)2,3,6-三乙基-β-环糊精、7)麦芽糖基-β-环糊精、8)磺丁醚-β-环糊精、9)对甲基苯磺氯(p-TsCl)取代的β-环糊精、10)6-位取代的β-CD对甲基苯磺酸酯(β-环糊精-6-OTs)、11)2-氧羟丙基-β-环糊精、12)2-位单取代的对甲基苯磺酸酯(β-环糊精-2-OTs)、13)β-环糊精对甲基苯磺酸酯(Tosyl-β-CD)j，以及14)β-环糊精的星形大分子PCL-(Tos)7-β-CD。
实施例199人参皂苷Rg3与人参皂苷Rg5组合物片剂的制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5组合物的片剂：
按上述配比，取实施例1-198中工艺路线制备的人参皂苷Rg3与人参皂苷Rg5组合物与淀粉混合均匀后，制成颗粒，加入滑石粉和硬脂酸镁混合均匀后压制成10000片。
实施例200人参皂苷Rg3与人参皂苷Rg5组合物颗粒剂的制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5组合物的颗粒剂：
人参皂苷Rg3与人参皂苷Rg5组合物(两者重量比为98:2) 100g
微晶纤维素 10000g
按上述配比，取实施例1-198中工艺路线制备的人参皂苷Rg3与人参皂苷Rg5组合物与微晶纤维素混合均匀后，制成颗粒装袋，制成10000袋。
实施例201人参皂苷Rg3与人参皂苷Rg5组合物胶囊剂制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5的组合物的胶囊剂：
人参皂苷Rg3与人参皂苷Rg5组合物(两者重量比为2:98) 250g
淀粉 2500g
按上述配比，取实施例1-198中工艺路线制备的人参皂苷Rg3与人参皂苷Rg5组合物与淀粉混合均匀后装胶囊，制成10000粒。
实施例202-205人参皂苷Rg3与人参皂苷Rg5组合物胶囊剂制备
人参皂苷Rg3与人参皂苷Rg5组合物组分按表5的重量比与淀粉混合均匀后装胶囊，各制成10000粒胶囊。
表5实施例202-205的原料配比
表中原料，可为实施例1-198中的人参皂苷Rg3与人参皂苷Rg5的组合物。
实施例206-209人参皂苷Rg3与人参皂苷Rg5组合物颗粒剂制备
人参皂苷Rg3与人参皂苷Rg5组合物组分按表6的重量比与微晶纤维素混合均匀后，制成颗粒装袋，制成10000袋。
表6实施例206-209的原料配比
表中原料，可为实施例1-198中的人参皂苷Rg3与人参皂苷Rg5的组合物。
实施例210人参皂苷Rg3与人参皂苷Rg5的组合物片剂制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5的组合物的片剂：
按上述配比，人参皂苷Rg3与人参皂苷Rg5组合物，与淀粉混合均匀后制成颗粒，加入滑石粉和硬脂酸镁混合均匀后压制成10000片。其中，本实施例中的人参皂苷Rg3与人参皂苷Rg5组合物可替换为实施例1-198中的人参皂苷Rg3与人参皂苷Rg5组合物。
实施例211人参皂苷Rg3与人参皂苷Rg5组合物颗粒剂制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5组合物的颗粒剂：
人参皂苷Rg3与人参皂苷Rg5组合物(两者重量比为2:98) 250g
甘草提取物 250g
微晶纤维素 24500g
按上述配比，人参皂苷Rg3与人参皂苷Rg5组合物与上述提取物粉末混合均匀，再与微晶纤维素混合均匀后制成颗粒装袋，制成10000袋。其中，本实施例中的人参皂苷Rg3与人参皂苷Rg5组合物可替换为实施例1-198中的人参皂苷Rg3与人参皂苷Rg5组合物。
实施例212人参皂苷Rg3与人参皂苷Rg5组合物胶囊剂制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5组合物的胶囊剂：
按上述配比，人参皂苷Rg3与人参皂苷Rg5组合物与上述提取物粉末混合均匀，再与淀粉混合均匀后装胶囊，制成10000粒。其中，本实施例中的人参皂苷Rg3与人参皂苷Rg5组合物可替换为实施例1-198中的人参皂苷Rg3与人参皂苷Rg5组合物。
实施例213人参皂苷Rg3与人参皂苷Rg5组合物片剂制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5组合物的片剂：
按上述配比，人参皂苷Rg3与人参皂苷Rg5组合物与上述提取物粉末混合均匀，再与淀粉混合均匀后制成颗粒，加入滑石粉和硬脂酸镁混合均匀后压，制成10000片。其中，本实施例中的人参皂苷Rg3与人参皂苷Rg5组合物可替换为实施例1-198制备的人参皂苷Rg3与人参皂苷Rg5组合物。
实施例214人参皂苷Rg3与人参皂苷Rg5组合物颗粒剂制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5组合物的颗粒剂：
按上述配比，人参皂苷Rg3与人参皂苷Rg5组合物与上述提取物粉末混合均匀，再与微晶纤维素混合均匀后制成颗粒装袋，制成10000袋。其中，本实施例中的人参皂苷Rg3与人参皂苷Rg5组合物可替换为实施例1-198制备的人参皂苷Rg3与人参皂苷Rg5组合物。
实施例215人参皂苷Rg3与人参皂苷Rg5组合物固体饮料制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5组合物的固体饮料：
人参皂苷Rg3与人参皂苷Rg5组合物(两者重量比为10:90) 1000g
糖粉 5000g
按上述配比，人参皂苷Rg3与人参皂苷Rg5组合物与上述提取物粉末混合均匀，制成颗粒装袋，制成10000袋。其中，本实施例中的人参皂苷Rg3与人参皂苷Rg5组合物可替换为实施例1-198制备的人参皂苷Rg3与人参皂苷Rg5组合物。
实施例216人参皂苷Rg3与人参皂苷Rg5组合物压片糖果制备
按照如下配比制备人参皂苷Rg3与人参皂苷Rg5组合物的固体饮料：
人参皂苷Rg3与人参皂苷Rg5组合物(两者重量比为10:90) 1000g
糖粉 5000g
按上述配比，人参皂苷Rg3与人参皂苷Rg5组合物与上述提取物粉末混合均匀，制成颗粒后压片，制成10000片。其中，本实施例中的人参皂苷Rg3与人参皂苷Rg5组合物可替换为实施例1-198制备的人参皂苷Rg3与人参皂苷Rg5组合物。
试验例1人参皂苷Rg3与Rg5组合物对小鼠提高免疫功能作用的探讨
1实验材料
1.1药物与试剂
人参皂苷Rg3与Rg5组合物，大连富生天然药物开发有限公司生产，并经高效液相色谱法测定Rg3与Rg5的含量。具体信息见表7。
表7试验例1所用组合物列表
阳性对照药：匹多莫德口服溶液(江苏吴中医药集团有限公司苏州制药厂，规格：10ml：400mg，批号2014091211)
1.2实验动物
昆明种小鼠，6-8W龄，体重18-22g，购自大连医科大学实验动物中心，质量合格证号：SCXK(13)2013-0003。
2实验方法
2.1分组及给药
取上述健康雄性小鼠290只，适应环境4d后按体重随机分成29组：阴性对照组，阳性药对照组，人参皂苷组合物实验组，其中人参皂苷组合物实验组又分别分成高剂量组、中剂量组、低剂量组。阳性对照组给匹多莫德(50mg/kg)，人参皂苷组合物组低剂量组(36mg/kg)，中剂量组(72mg/kg)，高剂量组(144mg/kg)，灌胃，各组每日给药1次，连续给药30d，阴性对照组给予同体积水。
2.2实验及实验结果
2.2.1ConA诱导小鼠脾淋巴细胞转化试验
末次给药后1h，各组动物无菌取脾，制备脾细胞悬液。将脾细胞悬液稀释到3×106个/mL的浓度后，将分成2份，将每一份脾细胞悬液分别置两个24孔培养板中，每孔1mL，一孔加入75μL ConA液(a)，另一孔作为对照(b)，37℃培养72h。培养结束前4h加入噻唑兰(MTT)。培养结束后加入酸性异丙醇，充分混匀后在570nm处测定各溶液的吸光度值(ABS)。计算增殖力(增殖力＝ABSa-ABSb)。受试样品各剂量组与阴性对照组进行比较。实验结果见表1。
2.2.2NK细胞活性测定
末次给药后1h，各组动物无菌取脾，制备脾细胞悬液。用灭菌注射用水裂解红细胞后，加入1％冰醋酸稀释细胞悬液。调整脾细胞悬液的浓度为2×107个/mL后，加入96孔板中培养。每个动物分成：反应孔(脾细胞悬液和YAC-1细胞悬液100μL，效靶比为50∶1)；自然释放孔(YAC-1细胞悬液和培养液各100μL)；最大释放孔(YAC-1细胞悬液和1％NP40各100μL)。以上各项均做3个平行管。96孔板在37℃，5％CO2培养箱中培养4h，加入LDH基质液和1moL/LHCl后，合并各平行孔的溶液，在490nm处测定吸光度(ABS)。计算NK细胞活性。NK细胞活性(％)＝(ABS反应孔-ABS自然释放孔)/(ABS最大释放孔-ABS自然释放孔)。实验结果见表8。
表8人参皂苷组合物对NK细胞活性以及ConA诱导淋巴细胞增殖能力的影响(x±s)
3试验结果
ConA刺激T淋巴细胞后使得母细胞发生增殖反应，其活细胞特别是增殖细胞中的线粒体水解酶将MTT分解为兰紫色结晶后，光密度值增大则表示细胞增强作用。由表1中可以看出，人参皂苷组合物高、中、低剂量组的光密度差值均高于阴性对照组的光密度差值，表明该样品具有促进脾细胞增殖的作用。
NK细胞对细胞进行杀伤后，活细胞胞浆内的LDH释放到细胞外时，LDH可使乳酸锂脱氢，进而使NAD还原成NADH，NADH经递氢体吩嗪二甲酯硫酸盐(PMS)还原碘硝基-氯化四氮唑(INT)，INT接受H+被还原成紫红色甲臜类化合物，经酶标仪测定光密度值。由表1中可以看出，人参皂苷组合物高、中、低剂量组的NK细胞活性均明显高于阴性对照组，表明该样品具有提高NK细胞活性的作用。
上述试验结果表明：人参皂苷Rg3与人参皂苷Rg5组合物各组不同剂量均具有促进脾细胞增殖的作用和提高NK细胞活性的作用；而且人参-连翘组合使用，具有协同增效作用，具有显著促进脾细胞增殖的作用和显著提高NK细胞活性的作用，能显著提高免疫功能。
试验例2人参皂苷组合物抗小鼠S180肉瘤试验
1实验材料
1.1实验动物及移植瘤株
昆明小鼠，由广东省医学实验动物中心提供，许可证号：SCXK2013-005；
S180肉瘤瘤株，购自广东省医学实验动物中心。
1.2药品
人参皂苷Rg3与Rg5组合物，大连富生天然药物开发有限公司生产，并经高效液相色谱法测定Rg3与Rg5的含量。
表9试验例2所用组合物列表
试验用药低、中、高剂量分别为临床成人等效剂量(按成人60kg体质量计算)的2倍、4倍及8倍，用双蒸水配成所需浓度的混悬液，配好的药液存避光4℃冰箱中备用。
阳性对照药：环磷酰胺(批号：20130105，江苏恒瑞医药股份有限公司)。为临床成人等效剂量(按成人60kg体质量计算)给药，用双蒸水配成所需的混悬液，配好的药液存避光4℃冰箱中备用。
2、实验方法
2.1分组及给药
取接种Sl80肉瘤7天生长良好的腹水型小鼠，在无菌操作下抽取腹水，用灭菌的生理盐水稀释，调节细胞数为2×106个/0.2mL，置于冰水中保存。
健康昆明小鼠120只(雌雄各半)，6-8W龄，体重18-22g，实验条件下预养1周后，随机取出10只作为空白对照组，其余的110只，每只左后肢腋窝皮下接种S180瘤细胞悬液0.2mL，接种24h后称重，随机分成11组：荷瘤对照组，阳性药对照组，人参皂苷组合物实验组，其中人参皂苷组合物实验组又分别分成高剂量组、中剂量组、低剂量组。于分组当天开始灌胃给药，人参皂苷组合物组低剂量组(36mg/kg)，中剂量组(72mg/kg)，高剂量组(144mg/kg)，阳性对照组给环磷酰胺45mg/kg；正常对照组，模型组给等量生理盐水，灌胃，1次/d。
造模用药后，观察每组小鼠的进食、饮水、毛色变化、活动情况、对刺激的反应、有无腹泻、消瘦、死亡等情况，并随时记录。灌胃给药后第21d停药，次日脱颈椎处死小鼠并称重，完整剥离左后肢皮下肿瘤组织，去除血污、脂肪等非肿瘤组织，用电子天平称瘤重，按下式计算抑瘤率：
抑瘤率＝(对照组平均瘤重-用药组平均瘤重)/对照组平均瘤重×100％
2.2数据以均数±标准差
表示，计量资料组间比较用SPASS13.0统计软件进行单因素方差分析，以P<0.05为具有显著性差异。
3、实验结果
3.1用药后动物一般情况观察
用药后各组小鼠均存活，空白对照组小鼠进食、饮水情况正常，活动灵活，反应灵敏，毛发光泽，无腹泻、消瘦情况。相比而言，人参皂苷组合物各给药组小鼠一般情况次之；阳性对照组小鼠进食较差，饮水少，活动缓慢，反应较迟钝，脱毛，毛色无光泽，有腹泻，消瘦；荷瘤对照组最差，可见小鼠进食很少，很少活动，反应迟钝，毛色枯槁，消瘦明显。
3.2各组间移植瘤重和抑瘤率见表10。
表10各组间移植瘤重和抑瘤率
试验结果表明，用药组移植瘤重明显低于荷瘤对照组，表明人参皂苷组合物A、B、C均具有抗移植性小鼠S180肉瘤的作用，且人参皂苷组合物A、D、G的抑瘤率达到50％以上，充分说明人参皂苷组合物可以抑制肿瘤的功效提高。
试验例3人参皂苷组合物抗肿瘤靶向耐药性实验
1材料与方法
人胆管癌细胞株QBC939:购于上海弘顺生物科技有限公司。
人参皂苷组合物大连富生天然药物开发有限公司，具体信息见表11。
表11试验例3所用组合物列表
2实验方法
2.1建立耐药细胞株
将人胆管癌细胞QBC939，复苏接种于装满细胞培养液的T25细胞培养瓶，并运用ADM持续接触浓度递增法建立QBC939/ADM。
2.2CCK-8法检测化疗药物对细胞的细胞毒作用
分组如下:设1组空白调零组、1组正常对照组、9组实验组，即含浓度为80μg/ml人参皂苷组合物的培养液100μl培养细胞。
对照组即化疗药组:每孔加入含化疗药物的培养液100μl，化疗药物为靶向药物阿法替尼(400μg/ml)、色瑞替尼(1000μg/ml)、厄洛替尼(200μg/ml)，每种药物设6个复孔。
实验组(化疗药+中药):每孔加入含化疗药物+人参皂苷组合物的培养液共100μl，即阿法替尼(400μg/ml)+人参皂苷组合物(80μg/ml)、色瑞替尼(1000μg/ml)+人参皂苷组合物(80μg/ml)、厄洛替尼(200μg/ml)+人参皂苷组合物(80μg/ml)，每种药物设6个复孔。
2实验结果
结果显示:24h后测定化疗药物的细胞毒作用，实验组细胞的OD值(吸光度)明显低于对照组，说明实验组的细胞活性明显低于对照组，化疗药物对实验组的细胞毒作用明显强于对照组，说明人参皂苷组合物实验组具有逆转耐药性的作用，结果见表12。
表12耐药性试验吸光度值数据
| 组别 | 阿法替尼 | 色瑞替尼 | 厄洛替尼 |
| 对照组 | 1.179±0.147 | 1.304±0.096 | 1.294±0.131 |
| 组合物A | 0.703±0.132 | 0.611±0.101 | 0.608±0.122 |
| 组合物B | 1.002±0.102 | 0.924±0.122 | 0.913±0.135 |
| 组合物C | 0.950±0.141 | 0.840±0.139 | 0.837±0.095 |
| 组合物D | 0.706±0.127 | 0.613±0.092 | 0.604±0.134 |
| 组合物E | 1.016±0.135 | 0.914±0.137 | 0.902±0.127 |
| 组合物F | 0.943±0.129 | 0.856±0.121 | 0.844±0.131 |
| 组合物G | 0.691±0.136 | 0.573±0.126 | 0.562±0.134 |
| 组合物H | 1.013±0.097 | 0.930±0.127 | 0.823±0.098 |
| 组合物I | 0.941±0.087 | 0.852±0.093 | 0.841±0.096 |
试验例4人参皂苷组合物缓解放化疗毒副作用(呕吐)的实验
1实验材料
1.1药物与试剂：
人参皂苷组合物，白色至棕黄色粉末，大连富生天然药物开发有限公司生产，以中国药品生物制品的对照品为外标，经高效液相色谱两种检测器紫外检测器从测定其含量。具体信息见表13。
表13试验例4所用组合物列表
阳性对照药：胃复安注射液(天津人民制药厂，规格：1ml：l0mg，批号14060129)；
高岭土(上海市奉贤奉城试剂厂，批号140528)；
大鼠高岭土的制备：称取阿拉伯胶1g加100mL蒸馏水，置于磁力搅拌器上搅拌至完全溶解；接着另取过80目筛的高岭土，慢慢加人上述溶液，边加边搅拌，和成面团状，用力将其挤压到5mL注射器内，让其完全塞满，制成边缘很光滑的小棒，其形状类似正常食物；然后放置于装有蓝色硅胶颗粒的干燥器内待其干燥后备用。
1.2实验动物：
Wistar大鼠，雄性，体重200～220g，由自大连医科大学实验动物中心提供，质量合格证号：SCXK(13)2013-0002。
2试验方法
大鼠为啮齿类动物，无呕吐反应，大鼠在遭受前庭刺激后出现异嗜行为相当于其他动物呕吐的一种反应，可作为大鼠运动病的典型症状。
2-1、大鼠适应性饲养
实验前，大鼠先进行适应性饲养，即将正常饲料与高岭土饲料定量后，同时给予大鼠，并每天定时将两种饲料取出称重，观察饲料表面有无咬痕，直到大鼠几乎不再啃食高岭土为止，开始进人正式实验。
2-2、异嗜实验
将Wistar大鼠随机分为29组，每组6只，即模型对照组；阳性药物对照组；人参皂苷组合物实验组，其中每个人参皂苷组合物实验组分为低、中、高三个剂量组。
模型对照组灌胃给予生理盐水10mL/kg；阳性药物对照组腹腔注射胃复安注射液2mg/kg；人参皂苷组合物低、中、高剂量组分别灌胃给予连翘苷15mg/kg、30mg/kg、60mg/kg；连翘苷衍生物A低、中、高剂量组分别灌胃给予人参皂苷组合物15mg/kg、30mg/kg、60mg/kg。
用药后30min给予旋转刺激，即采用离心机改装的诱发运动病的旋转刺激装置，旋转速度l00r/min，旋转1h。
观察各组大鼠在停止旋转后24h内大鼠的异嗜高岭土行为，并记录正常饲料和高岭土的耗用量。
3试验结果
实验中所有数据均采用均数±标准差(X±S)表示，并采用PPMS医学统计学软件对结果进行方差分析和P检验。
正常饲料和高岭土的耗用量统计结果如表14所示。
表14人参皂苷组合物对旋转致大鼠异嗜作用的影响(X±s，n＝6)
实验结果表明：
放化疗最主要的副作用就是呕吐，可以体现为大鼠异嗜高岭土。人参皂苷组合物各剂量组均对大鼠异嗜高岭土行为有明显抑制作用，异嗜高岭土的量与空白对照组比较有明显减少(P<0.05，P<0.01)。人参皂苷组合物各剂量组均可显著增加大鼠食物摄入量。上述实验说明人参皂苷组合物在缓解放化疗引起的呕吐方面效果显著，具有较好的临床应用前景。
实施例5人参皂苷组合物治疗抑郁症药效学实验
1材料
人参皂苷Rg3与人参皂苷Rg5组合物，大连富生天然药物开发有限公司生产，批号：20120316；以中国药品生物制品检定所提供的标准品对照并进行HPLC测定。
表15试验例5所用组合物列表
盐酸氟西汀片(常州四药制药有限公司，批号20100623)。根据“按人与动物等效剂量的折算方法”。
皮质醇(CORT)酶免试剂盒和肾上腺皮质激素(ACTH)酶免试剂盒(均为美国RD公司，批号20111201B)。
自制的敞箱；电击仪、HY一5型回旋振荡器(金坛市天竞实验仪器厂)、FA2004A型电子天平(上海精天电子仪器有限公司)、Bio-rad680型酶标仪(美国，伯乐公司)等。
动物SPF级雄性Wistar大鼠300只，体重(180±20)g，由山东省动物实验中心提供，许可证号SCXK(鲁)2008-0002。
2方法
2.1动物分组与模型复制
大鼠经过1周的适应性喂养，对每只大鼠进行敞箱实验(open—field test)和糖水消耗训练实验。
对敞箱实验水平运动和垂直运动总得分低于30分或高于120分的大鼠予以剔除。根据敞箱实验结果编号，随机分为5组，每组10只，分为空白对照组、模型组、阳性药盐酸氟西汀组、人参皂苷Rg3与人参皂苷Rg5组合物试验组(每个实验组分为低、中、高三个剂量组)。采用慢性轻度不可预见性应激结合孤养的复合模型，并结合预实验结果加以改进。
模型制作的应激处理参照文献[1、夏军，叶慧，周义成，等.慢性应激大鼠抑郁模型的建立及其有效性的探讨[J].华中科技大学学报：医学版，2005，34(4)：495.2、王建醒，周丽，徐华锋，等.慢性应激大鼠抑郁模型的建立及评价[J].齐齐哈尔医学院学报，2006，27(6)：646.]改进如下：电击足底(20V电压，每次持续10S，延迟10S，20次，共3次)、冰水游泳(4℃，持续5min，共3次)、热刺激(45℃，持续5min，共3次)、水平震荡(速率1次/S，5min，共3次)、夹尾(持续1min，共3次)、禁水(24h，共3次)、禁食(24h，共3次)、昼夜颠倒(共2次)、潮湿垫料(共2次)、束缚(持续5h，共3次)、明暗循环(频闪照射120次/m，12h，共3次)、通宵照明(共3次)、合笼(共3次)、禁水禁食(24h，共3次)、休息(共2次)，将以上不同应激因子在实验全程中随机运用，使大鼠不可预见刺激的发生，平均每种刺激使用最多不超过3次，相邻2d的刺激不能重复，同时配合单笼(正常组除外)饲养，共刺激42d。
空白对照组大鼠单笼饲养，正常进食和喝水，不做任何刺激。
2.2给药方法 盐酸氟西汀组2.5mg.kg-1、人参皂苷Rg3与人参皂苷Rg5组合物分别为1.02，2.04，4.08mg.kg-1，各组均按10mL.kg-1ig(灌胃)给药，空白对照组和模型组按10mL.kg-1生理盐水ig，1次/d，每天应激前灌胃给药，从造模第22天开始，至动物处死当天，共给药21d，给药期间，各造模组大鼠均继续给予刺激。
2.3标本的制备及检测 各组动物试验给药、末次造模结束后，禁水禁食24h，10％水合氯醛ip麻醉，腹主动脉采血6mL，其中3mL放入加10％EDTA-Na230μL和抑肽酶20μL的试管内，混匀，4℃，3000r.min-1，离心10min，分离血浆，置于-70℃冰箱保存，待测ACTH；另3mL放入加入肝素钠40μL的试管，混匀，4℃，3000r.min-1，离心10min，分离血浆，置于-20℃冰箱保存，待测CORT。采用放射免疫分析法(RIA)测定大鼠血浆CORT和ACTH的变化。
2.4统计方法 以SPSS 17.0FOR Windows统计软件包作为统计工具，各项指标结果采用表示，组间数据比较若符合正态分布采用完全随机设计资料单因素方差分析两两样本比较，其中方差齐者采用LSD法检验，方差不齐者采用Dunnett’sT3法检验。P<0.05为有统计学意义。
3结果
模型组大鼠血浆CORT和ACTH的水平显著高于空白对照组(P<0.05)，有统计学意义，说明抑郁模型动物存在HPA(下丘脑-垂体-肾上腺皮质)轴的异常兴奋；经过治疗后，各组大鼠CORT和ACTH的水平明显低于模型组水平(P<0.05)。试验结果见表16。
表16 20(R)-人参皂苷Rg3对抑郁模型大鼠血浆CORT和ACTH含量的影响(x±s,n＝10)
表1的实验结果显示：模型组大鼠血浆CORT和ACTH的水平显著高于空白对照组(P<0.05)，经过药物干预后，各组大鼠CORT和ACTH的水平明显低于模型组水平(P<0.05)。说明药物对抑郁症有明显的治疗作用。
实施例6人参皂苷组合物抗疲劳试验
1实验材料
1.1药物与试剂
SOD活性测定试剂盒南京建成生物工程技术公司
人参皂苷Rg3与人参皂苷Rg5组合物，大连富生天然药物开发有限公司生产，批号：20120316；以中国药品生物制品检定所提供的标准品对照并进行HPLC测定。
表17试验例6所用组合物列表
1.2实验动物：
BALB/C裸鼠，重量26-28g，6周龄，购自北京维通利华实验动物中心。
2.实验方法
2.1分组及给药：
筛选后的雄性小鼠280只，常规饲养8周，适应性喂养1周，运动训练1周。
按体重随机分成28组：对照组，人参皂苷组合物实验组，其中人参皂苷组合物实验组又分别分成高剂量组、中剂量组、低剂量组。
对照组给生理盐水，人参皂苷组合物组低剂量组(3.2mg/kg)，中剂量组(6.4mg/kg)，高剂量组(12.8mg/kg)，灌胃，各组每日给药1次，连续给药30d。
2.3实验及实验结果
力竭游泳实验
游泳池的规格为185㎝×73㎝×58㎝，游泳时水深30㎝，水温27±1℃。将裸鼠置入游泳池，记录裸鼠从入水游泳至精疲力竭(小鼠有用动作明显失调，头部沉入水中8秒不能浮出水面为力竭标准)的时间。
SOD活性测定
血液SOD活性是反应计提抗疲劳的重要指标，采用此法可以评价疲劳指数。
表18力竭游泳试验与SOD数据表
表中数据表明，人参皂苷组合物实验组小鼠的力竭游泳时长明显长与对照组，其SOD活性明显高于力竭游泳运动组，差异显著，说明人参皂苷组合物具有明显的抗疲劳作用。
Claims (12)
1.一种人参皂苷Rg3与人参皂苷Rg5的组合物的制备方法，及其在提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳、抗抑郁的药品、食品和保健品中的应用。
2.如权利要求1所述人参皂苷Rg3与人参皂苷Rg5的组合物，其特征是人参皂苷Rg3与人参皂苷Rg5比例为1～99:1～99。
3.如权利要求1所述的人参皂苷Rg3与人参皂苷Rg5的组合物，其特征是以人参与其他中药材经特定工艺制成的混合物组成。
4.如权利要求3所述的混合物，其特征是人参皂苷Rg3与人参皂苷Rg5的重量在混合物中的总重量的比例为1％～100％。
5.复合组合物，其为人参与其他中药材经特定工艺制成的提取物与药学上或食品上可接受的载体、经过物理或者化学方法制成的复合物。
6.如权利要求5所述的复合组合物，其特征是人参与其他中药材经特定工艺制成的提取物的重量与药学上可接受的载体的重量之比为1:1～1:100。
7.根据权利要求2中所述的其他中药材，其特征是可以是桑葚、炒枳壳、白芍、佛手、藕节、炒枳实、白果、柿蒂、草乌叶、莲房、椿皮、侧柏叶、石榴皮、山茱萸、五倍子、白及、白附子、川楝子、天花粉、党参、紫鸢、青蒿、皂刺、小茴、地肤子、桃仁、乌梅、仙灵脾、鸡内金、生地、山药、秦艽、沙参、石韦、丹参、牵牛子、胡芦巴、扁豆、苏子、清半夏、黄连、补骨脂、黄柏、元胡、青果、墨旱莲、木瓜、马齿苋、香橼、牛膝、覆盆子、何首乌、秦皮、棕榈、莲子、仙鹤草、青梅、白帆、罂粟壳、诃子、金樱子、地榆、杏仁、青皮、栀子、女贞子、熟地、黄芩、芦根、黄芪、莪术、桑白皮、麦冬、槟榔、生乳香、鸡血藤、白术、地骨皮、当归、乌梅、麦芽、枇杷叶、柏子仁、桂皮、天冬、生没药、桔梗、茅根、制附子、菊花、木香、百步、三棱、杜仲、陈皮、大黄、大腹皮、天麻、太子参、赤芍、旋复花、夏枯草、菟丝子、骨碎补、郁金、南星、蒲公英、甘草、升麻、地丁、茜草、乌药、五加皮、川乌、荔枝壳、余甘子、射干、大青叶、吴茱萸、红花、香附、五味子、酸枣仁、山楂、紫草等。
8.如权利要求4中所述的特定工艺，其特征是人参与上述中药材的一种、两种、或两种以上，一起以水加热提取、浓缩、除杂，重结晶等步骤，由此制备方法获得的提取物的一系列操作。
9.如权利要求5所述的药品，其特征是以片剂、胶囊剂、丸剂、散剂、颗粒剂、糖浆剂、溶液剂、乳剂、注射剂、喷雾剂、气雾剂、凝胶剂、霜剂、巴布剂、橡胶贴膏剂或贴膏剂形式存在。
10.如权利要求5所述的食品，其特征是以乳制品、糖果、饮料、饼干、茶叶及相关制品、酒等食品形式存在。
11.如权利要求5所述的保健品，其特征是以片剂、胶囊剂、丸剂、散剂、颗粒剂、糖浆剂、溶液剂、乳剂、喷雾剂、气雾剂、凝胶剂、霜剂、巴布剂、橡胶贴膏剂或贴膏剂形式存在，或者以乳制品、糖果、饮料、饼干、茶叶及相关制品、酒等食品形式存在。
12.如权利要求1所述的在提高免疫、抗肿瘤、抗肿瘤靶向药物的耐药性、减轻放化疗毒副反应、抗疲劳及抗抑郁的应用。
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| JP2023513098A JP2023538664A (ja) | 2020-08-25 | 2021-08-20 | ジンセノサイドＲｇ３およびジンセノサイドＲｇ５の組成物ならびに抗腫瘍効果を含むその医薬用途 |
| CA3190378A CA3190378A1 (en) | 2020-08-25 | 2021-08-20 | Compositions of ginsenoside rg3 and ginsenoside rg5 and their pharmaceutical uses including anti-tumor effects |
| US18/022,372 US20230321125A1 (en) | 2020-08-25 | 2021-08-20 | Compositions of ginsenoside rg3 and ginsenoside rg5 and their pharmaceutical uses including anti-tumor effects |
| BR112023003331A BR112023003331A2 (pt) | 2020-08-25 | 2021-08-20 | Composições de ginsenosídeo rg3 e ginsenosídeo rg5 e seus usos farmacêuticos, incluindo efeitos antitumorais |
| EP21860266.2A EP4205748A1 (en) | 2020-08-25 | 2021-08-20 | Composition of ginsenosides rg3 and rg5 and anti-tumor pharmaceutical use thereof |
| KR1020237010339A KR20230057438A (ko) | 2020-08-25 | 2021-08-20 | 진세노사이드 Rg3과 진세노사이드 Rg5의 조성물 및 항종양 효과를 포함하는 이의 약학적 용도 |
| CN202180056132.4A CN116096393A (zh) | 2020-08-25 | 2021-08-20 | 人参皂苷Rg3与Rg5的组合物及其抗肿瘤等药用 |
| PCT/CN2021/113658 WO2022042428A1 (zh) | 2020-08-25 | 2021-08-20 | 人参皂苷Rg3与Rg5的组合物及其抗肿瘤等药用 |
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| CN202180056132.4A Pending CN116096393A (zh) | 2020-08-25 | 2021-08-20 | 人参皂苷Rg3与Rg5的组合物及其抗肿瘤等药用 |
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| EP (1) | EP4205748A1 (zh) |
| JP (1) | JP2023538664A (zh) |
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| CN (2) | CN112245443A (zh) |
| BR (1) | BR112023003331A2 (zh) |
| CA (1) | CA3190378A1 (zh) |
| WO (1) | WO2022042428A1 (zh) |
Cited By (7)
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| CN112121071A (zh) * | 2020-09-29 | 2020-12-25 | 吉林瑞诺科技有限公司 | 一种以人参为原料制备的产品 |
| CN112294830A (zh) * | 2020-09-29 | 2021-02-02 | 吉林瑞诺科技有限公司 | 一种富集稀有人参皂苷的西洋参叶产品 |
| CN112315989A (zh) * | 2020-09-29 | 2021-02-05 | 吉林瑞诺科技有限公司 | 一种富集稀有人参皂苷的西洋参产品 |
| CN112315967A (zh) * | 2020-09-29 | 2021-02-05 | 吉林瑞诺科技有限公司 | 一种三七产品 |
| CN112315968A (zh) * | 2020-09-29 | 2021-02-05 | 吉林瑞诺科技有限公司 | 一种富含稀有人参皂苷的人参叶产品 |
| CN112656828A (zh) * | 2020-09-29 | 2021-04-16 | 吉林瑞诺科技有限公司 | 一种三七叶产品 |
| WO2022042428A1 (zh) * | 2020-08-25 | 2022-03-03 | 大连富生天然药物开发有限公司 | 人参皂苷Rg3与Rg5的组合物及其抗肿瘤等药用 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116120389B (zh) * | 2023-03-29 | 2023-07-18 | 中国农业科学院特产研究所 | 人参皂苷Rg5及制备和在制备过敏性鼻炎药物中的应用 |
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Also Published As
| Publication number | Publication date |
|---|---|
| BR112023003331A2 (pt) | 2023-04-04 |
| CA3190378A1 (en) | 2022-03-03 |
| WO2022042428A1 (zh) | 2022-03-03 |
| US20230321125A1 (en) | 2023-10-12 |
| CN116096393A (zh) | 2023-05-09 |
| JP2023538664A (ja) | 2023-09-08 |
| KR20230057438A (ko) | 2023-04-28 |
| EP4205748A1 (en) | 2023-07-05 |
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