CN101156882A - 三七原人参二醇型皂苷制备方法及其用途 - Google Patents
三七原人参二醇型皂苷制备方法及其用途 Download PDFInfo
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- CN101156882A CN101156882A CNA2007101561889A CN200710156188A CN101156882A CN 101156882 A CN101156882 A CN 101156882A CN A2007101561889 A CNA2007101561889 A CN A2007101561889A CN 200710156188 A CN200710156188 A CN 200710156188A CN 101156882 A CN101156882 A CN 101156882A
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- radix notoginseng
- saponin
- ethanol elution
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供一类来源于五加科植物三七的提取物的制备方法，该类提取物主要含有达玛烷型四环三萜类原人参二醇型皂苷类提取物，其中人参皂苷Rb1和Rd的含量不低于60％，人参皂苷Re、Rg1和三七皂苷R1的含量不高于5％。通过用含水乙醇为溶剂对三七进行提取，提取液经色谱柱层析得洗脱液，用反相液相色谱梯度洗脱，收集洗脱液经浓缩得到目的提取物。本发明的提取工艺能有效去除糖、蛋白质、氨基酸，三七原人参三醇型皂苷等杂质，提高有效成分的含量，有效成分确切，工艺简单，质量可控，适合工业化生产。可在制备治疗恶性实体瘤的药物中应用。
Description
技术领域
本发明属中药提取物，涉及从中药三七中提取的二醇式达玛烷型四环三萜类皂苷提取物，该提取物具有抑制血管生成的作用，可用于恶性实体瘤的防治。
技术背景
肿瘤的大小超过0.2mm时，开始建立自身的血液供应系统，即新的血管生成(angiogenesis)。血管生产是生长出新的微细血管，这个过程主要依赖毛细血管内皮细胞的迁移、增殖和管腔形成。在正常生理条件下，血管生成严格受控于内源性血管生成因子与抗血管生成因子二者之间的平衡；而肿瘤的“血管生成启动”是以癌基因激活肿瘤表达血管生成因子的前体蛋白为特征的，包括VEGF、bFGF、IL-8、PDGF等等，与肿瘤缺氧相关的缺氧条件也能激活缺氧诱导因子HIF-1α，后者能诱导血管生成因子的上调。
异常的血管生成是肿瘤的一个显著特征。常规的抗肿瘤药物常因耐药性使其疗效收到一定限制，而且往往带来严重的毒副作用，抗血管生成的药物能够克服这些抗肿瘤药物的弊端，抑制肿瘤新的血管形成可使肿瘤细胞的营养不足，限制肿瘤的快速生长。因此可以用于抗肿瘤治疗。
作为一类靶向抗肿瘤药物，血管生成抑制剂的研究与开发在世界范围内受到广泛关注。当前，全球至少有30多种血管生成抑制剂已经进入临床研究，其中恩度(Endostatin)、阿瓦斯汀(Avastin)等已经批准上市，取得了一定的治疗效果。但是，这类药物往往需要采取注射给药方式，且储存和运输条件苛刻。同时，这些药物价格通常相当昂贵，患者的经济负担很沉重。因此，需要继续开发疗效确切、使用方便、价格低廉的血管生成抑制剂。
三七为五加科(Araliaceae)多年生草本植物三七(Panax notoginseng(Burk.)F.H.Chen)的根，主产于云南、广西及四川等地。三七总皂苷(Panax notoginoside，PNS)是三七主要活性成分，其含量约10％左右。其主要活性成分是达玛烷型20(S)-原人参二醇型(ppd)和20(S)-原人参三醇型(ppt)四环三萜皂苷，二者区别在于原人参二醇型皂苷B环6位无羟基取代而原人参三醇型B环有一羟基取代。三七中原人参二醇型皂苷主要包括人参皂苷Rb1和Rd，原人参三醇型皂苷主要包括人参皂苷Re和Rg1，三七皂苷R1等。
虽然有许多三七及其成分抗肿瘤的报道，但一般认为，主要是通过调节机体免疫功能，改善生理机能发挥作用的。另外，三七皂苷及其相关的化学物质对于多种化疗导致的毒副作用具有减轻或拮抗的作用。此前，各项研究均未将三七中原人参二醇型和原人参三醇型皂苷分开进行生物活性研究。
发明内容
本发明的目的是提供来源于五加科植物三七(Panax notoginseng(Burk.)F.H.Chen)的三七原人参二醇型皂苷制备方法，用本发明方法制备获得的提取物主要含有达玛烷型四环三萜类原人参二醇型皂苷类提取物，其活性组成包括人参皂苷Rb1和Rd等，其活性组成人参皂苷Rb1和Rd在提取物中含量不低于60％，提取物中还含原人参三醇型皂苷，其人参皂苷Re、Rg1和三七皂苷R1总含量不高于5％。所有含量用HPLC法，外标法测定。
本发明通过以下步骤实现：
(1)用含水乙醇作为溶剂对三七进行提取；
(2)提取液经过色谱柱层析得洗脱液；
(3)用反相液相色谱梯度洗脱，收集洗脱液经浓缩得到目的提取物。
其中步骤(1)中三七药材粉碎为粉末(过20目筛)至粗颗粒(粒径约1cm)状，提取液乙醇浓度为0-95％，溶剂用量5-20倍量，加热提取1-3次，每次0.5-2小时，最佳工艺为药材粉碎至颗粒状(3mm-8mm)，70％乙醇10-12倍溶剂量提取2次，每次2小时。
步骤(2)具体为样品上树脂后，先用水冲洗3-6个柱体积(BV)，再用0.05％-3％氨水冲洗3-6BV，再用水冲洗至pH＝7，用20-50％乙醇洗脱4-8BV，最后用30-80％乙醇洗脱4-8BV，收集最后洗脱液，浓缩，干燥。最优步骤为以大孔树脂D101为载体上样，先用水冲洗4-5个柱体积(BV)，再用0.05-0.1％氨水冲洗4-5BV，再用水冲洗至pH＝7，再用40％乙醇冲洗4-5BV，最后用70％乙醇洗脱5-6BV，收集洗脱液，浓缩，干燥。
步骤(3)具体为将样品上反相填料柱(包括ODS C8和ODS C18等填料)，先用0-40％的乙醇洗脱3-4 BV，再用20-70％的乙醇洗脱3-5BV，收集洗脱液，浓缩，干燥。最优步骤为将样品上反相填料ODS C18，吸附后先以20-25％乙醇洗脱3-4 BV，再以40-50％乙醇洗脱3-5 BV，收集洗脱液，回收溶剂，以水溶解后上大孔树脂D101，分别以30％，70％乙醇洗脱3 BV，收集70％乙醇洗脱液干燥即得。
本发明提取物含量测定方法如下：
色谱条件色谱柱Agilent Extend-C18柱(4.6mm×250mm，5μm)；采用梯度洗脱，流动相A相为水，流动相B相为乙腈，洗脱梯度：0min，20％B；30min，20％B；55min，46％B；65min，55％B；70min，55％B；72min，95％B；80min，95％B。流速1.0mL·min-1；检测波长203nm；柱温15℃；进样量5μL。
供试品溶液的制备称取本品，用甲醇溶液溶解在容量瓶中，稀释至刻度，摇匀，即得。
测定方法精密吸取供试品溶液，注入液相色谱仪，测定，即得。
按照测定方法，人参皂苷Rb1和Rd在提取物中含量不低于60％。提取物中所含原人参三醇型皂苷，如人参皂苷Re和Rg1，三七皂苷R1等的总量不高于5％。
该提取物也可以从其它植物如人参、西洋参等提取制得。
本发明提供的提取物，可以作为原料进一步水解、或化学修饰，生成相应的衍生物。也可以作为原料制成胶囊、片剂、口服液、颗粒剂、滴丸等多种剂型的药物。或与其它药物组合使用。
本发明还提供用本发明的中药有效提取物作为药物活性成分制备成的药物组合物，本发明的有效提取物，根据需要该组合物还可以加入药物可接受的载体。
本发明的有效提取物，是单位剂量的药物制剂形式，所述单位剂量形式是指制剂的单位，如片剂的每片，胶囊的每粒胶囊，口服液的每瓶，颗粒剂每袋等。
本发明的组合物其中的有效组分，其在制剂中所占重量百分比可以是0.1-99.9％，其余为药物可接受的载体。
本发明的组合物，通过将上述有效组分和药物可接受的载体混合制备得到。
本发明的组合物，其药物制剂形式可以是任何可药用的剂型，这些剂型包括：片剂、糖衣片剂、薄膜衣片剂、肠溶衣片剂、胶囊剂、硬胶囊剂、软胶囊剂、口服液、口含剂、颗粒剂、冲剂、丸剂、散剂、膏剂、丹剂、混悬剂、粉剂、溶液剂、注射剂、栓剂、软膏剂、硬膏剂、霜剂、喷雾剂、滴剂、贴剂。本发明的制剂，优选的是口服剂型，如：胶囊剂、片剂、口服液、颗粒剂、丸剂、散剂、丹剂、膏剂等。
本发明的组合物，其口服给药的制剂可含有常用的赋形剂，诸如粘合剂、填充剂、稀释剂、压片剂、润滑剂、崩解剂、着色剂、调味剂和湿润剂，必要时可对片剂进行包衣。
适用的填充剂包括纤维素、甘露糖醇、乳糖和其它类似的填充剂。适宜的崩解剂包括淀粉、聚乙烯吡咯烷酮和淀粉衍生物，例如羟基乙酸淀粉钠。适宜的润滑剂包括，例如硬脂酸镁。适宜的药物可接受的湿润剂包括十二烷基硫酸钠。
可通过混合，填充，压片等常用的方法制备固体口服组合物。进行反复混合可使活性物质分布在整个使用大量填充剂的那些组合物中。
口服液体制剂的形式例如可以是水性或油性悬浮液、溶液、乳剂、糖浆剂或酏剂，或者可以是一种在使用前可用水或其它适宜的载体复配的干燥产品。这种液体制剂可含有常规的添加剂，诸如悬浮剂，例如山梨醇、糖浆、甲基纤维素、明胶、羟乙基纤维素、羧甲基纤维素、硬脂酸铝凝胶或氢化食用脂肪，乳化剂，例如卵磷脂、脱水山梨醇一油酸酯或阿拉伯胶；非水性载体(它们可以包括食用油)，例如杏仁油、分馏椰子油、诸如甘油的酯的油性酯、丙二醇或乙醇；防腐剂，例如对羟基苯甲酯或对羟基苯甲酸丙酯或山梨酸，并且如果需要，可含有常规的香味剂或着色剂。
对于注射剂，制备的液体单位剂型含有本发明的活性物质和无菌载体。根据载体和浓度，可以将此化合物悬浮或者溶解。溶液的制备通常是通过将活性物质溶解在一种载体中，在将其装入一种适宜的小瓶或安瓿前过滤消毒，然后密封。辅料例如一种局部麻醉剂、防腐剂和缓冲剂也可以溶解在这种载体中。为了提高其稳定性，可在装入小瓶以后将这种组合物冰冻，并在真空下将水除去。
本发明的有效提取物，在制备成药剂时可选择性的加入适合的药物可接受的载体，所述药物可接受的载体选自：甘露醇、山梨醇、焦亚硫酸钠、亚硫酸氢钠、硫代硫酸钠、盐酸半胱氨酸、巯基乙酸、蛋氨酸、维生素C、EDTA二钠、EDTA钙钠，一价碱金属的碳酸盐、醋酸盐、磷酸盐或其水溶液、盐酸、醋酸、硫酸、磷酸、氨基酸、氯化钠、氯化钾、乳酸钠、木糖醇、麦芽糖、葡萄糖、果糖、右旋糖苷、甘氨酸、淀粉、蔗糖、乳糖、甘露糖醇、硅衍生物、纤维素及其衍生物、藻酸盐、明胶、聚乙烯吡咯烷酮、甘油、土温80、琼脂、碳酸钙、碳酸氢钙、表面活性剂、聚乙二醇、环糊精、β-环糊精、磷脂类材料、高岭土、滑石粉、硬脂酸钙、硬脂酸镁等。
本发明的组合物在使用时根据病人的情况确定用法用量，可每日服二至三次，每次1-10剂，如：1-10袋或粒或片。
本发明的另一个目的是提供的含有达玛烷型四环三萜类原人参二醇型皂苷类提取物在制备治疗恶性实体瘤的药物中应用。
本发明的有益效果为：
1.本发明的提取分离工艺中结合树脂填料和反相填料的优势，能有效地除去糖、蛋白质、氨基酸，三七原人参三醇型皂苷等杂质，提高有效成分的含量，其工艺简单，适合工业化生产。
2.本发明提供的有效提取物三七原人参二醇型皂苷成分简单明确，使用高效液相法测定其含量，对其有效成分含量和无效成分进行控制，在生产中更易于药物的质量控制。
3.本发明提供的有效提取物三七原人参二醇型皂苷，由于成分确切，含量明确，活性确切，制备工艺便捷，质量可控，适宜开发成为一种新抗肿瘤中药新药。
4.更新了对三七皂苷的传统认识，本发明提出三七所含的原人参二醇型皂苷具有抑制血管生成的效果，对于离体培养的人肿瘤细胞没有直接杀伤或抑制作用，但却能明显抑制移植性小鼠肿瘤的生长。根据研究未观察到原人参三醇型具有相同的这些作用，甚至显示一定的促进肿瘤生长的作用。
具体实施方式
为了更好地理解本发明的内容，以下以结合实施例作进一步的说明，但并不限制本发明的范围。
实施例1
三七药材粉碎至颗粒状(3mm-8mm)，70％乙醇10倍溶剂量提取2次，每次2小时。提取液浓缩至1g生药/ml，上大孔树脂D101，先用水冲洗3-5个柱体积(BV)，再用0.05-0.1％氨水冲洗4-5BV，再用水冲洗至pH＝7，再用40％乙醇冲洗3BV，最后用70％乙醇洗脱3-5BV，收集70％乙醇洗脱液，浓缩，干燥。将样品以水溶解，上反相填料柱ODS C18先以20-25％乙醇洗脱3-4 BV，再以40-50％乙醇洗脱3-5 BV，收集洗脱液，回收溶剂，干燥，以水溶解后上大孔树脂D1 01，分别以30％，70％乙醇洗脱3BV，收集70％乙醇洗脱液干燥即得。
实施例2
三七药材粉碎至颗粒状(3mm-8mm)，70％乙醇10倍溶剂量提取2次，每次2小时。提取液浓缩至1g生药/ml，上大孔树脂D101，先用水冲洗3-5个柱体积(BV)，再用0.05-0.1％氨水冲洗4-5BV，再用水冲洗至pH＝7，再用40％乙醇冲洗3BV，最后用70％乙醇洗脱3-5BV，收集70％乙醇洗脱液，浓缩，干燥。将样品以水溶解，上反相填料柱ODS C8先以15-20％乙醇洗脱3-4 BV，再以20-40％乙醇洗脱3-5 BV，收集洗脱液，回收溶剂，干燥，以水溶解后上大孔树脂D101，分别以30％，70％乙醇洗脱3BV，收集70％乙醇洗脱液干燥即得。
实施例3
三七药材粉碎至颗粒状(3mm-8mm)，70％乙醇10倍溶剂量提取2次，每次2小时。提取液浓缩至1g生药/ml，上大孔树脂D201，先用水冲洗3-5个柱体积(BV)，再用30％乙醇冲洗3BV，最后用70％乙醇洗脱3-5BV，收集70％乙醇洗脱液，浓缩，干燥。将样品以水溶解，上反相填料柱ODS C18先以20-25％乙醇洗脱3-4 BV，再以40-50％乙醇洗脱3-5 BV，收集洗脱液，回收溶剂，干燥，以水溶解后上大孔树脂D101，分别以30％，70％乙醇洗脱3BV，收集70％乙醇洗脱液干燥即得。
实施例4
三七药材粉碎至颗粒状(3mm-8mm)，70％乙醇10倍溶剂量提取2次，每次2小时。提取液浓缩至1g生药/ml，上大孔树脂AB-8，先用水冲洗3-5个柱体积(BV)，再用30％乙醇冲洗3BV，最后用70％乙醇洗脱3-5BV，收集70％乙醇洗脱液，浓缩，干燥。将样品以水溶解，上反相填料柱ODS C8先以15-20％乙醇洗脱3-4BV，再以20-40％乙醇洗脱3-5BV，收集洗脱液，回收溶剂，干燥，以水溶解后上大孔树脂D101，分别以30％，70％乙醇洗脱3BV，收集70％乙醇洗脱液干燥即得。
实施例5
片剂的制备，取实施例一中有效提取物三七原人参二醇型皂苷适量与微晶纤维素混合均匀，加3％聚维酮乙醇溶液制软材，过18目筛制颗粒，60℃干燥1小时，整粒，加入滑石粉适量，混匀，压片，即得。
实施例6
胶囊剂的制备，取实施例一中有效提取物三七原人参二醇型皂苷与花生油按2∶18的比例水溶式不锈钢搅拌灌中，同时加入适量明胶和甘油混合，放出再用胶体磨磨浆，磨出的混合液搅拌，制成药液；将甘油与蒸馏水在40-50℃温度下搅拌混溶，再将甘油液温至80-90℃，取明胶加入其中混合搅拌，直至全部溶化成胶液，然后在60℃温度下使胶液静置4小时，用制板机制成胶板供制丸工序使用；将上述制成的药液和胶板送入压丸机制丸，然后在22-25℃温度下吹风4小时作滚筒定型，又在25-30℃温度下吹风干燥16-20小时，检选合格胶丸，用95％乙醇清洗，在25-30℃下吹风干燥4小时，即得。
实施例7
注射剂的制备，取有效提取物三七原人参二醇型皂苷适量用40℃注射用水溶解，加入适量药用载体等渗剂，调节溶液的pH值为7.0-8.0，加注射用水至全量，用超滤器超滤除热源，测定pH值后，用膜过滤，分装后，高压灭菌，检验、包装，即得。
实施例8
滴丸的制备，取有效提取物三七原人参二醇型皂苷0.5g与10.5g聚乙二醇-6000混合均匀，加热熔融，化料后移至滴丸滴灌中，药液滴至6～8℃液体石蜡中，除油，制得滴丸300粒。
实施例9药理实验
一.有效提取物三七原人参二醇型皂苷对鸡胚血管形成的影响
取受精鸡胚，37℃孵育5天，可见心脏搏动。在鸡蛋气囊处开1.5×1.5cm窗口，在靠近尿囊血管稀疏处，小心覆盖浸润药物的滤纸片，同时设溶剂对照组。培养48h后，丙酮∶甲醇＝1∶1固定10min，揭下包含滤纸片区域的尿囊膜，置载玻片上，显微镜下观测毛细血管形成情况。以滤纸片1mm范围内血管数目计算抑制率。
表1有效提取物三七原人参二醇型皂苷对鸡胚血管形成的影响
| 组别 | 血管形成数 | 抑制率 |
| 溶剂对照组DMSO三七原人参二醇型皂苷1μg | 65.4±26.535.2±33.4* | 46.2％ |
| 三七原人参二醇型皂苷2μg | 29.7±14.2* | 54.6％ |
*与对照组相比，P＜0.05
二.有效提取物三七原人参二醇型皂苷对VEGF诱导的人脐带内皮细胞趋化作用的影响
分离培养人脐带静脉内皮细胞，生长至第3代后使用。在24孔Transwell(8μm孔径，实现用0.1％明胶包被)板上进行趋化实验。在上腔中，每孔加入内皮细胞50000个，下腔加入M199培养液，含VEGF(165aa)5ng/ml，20h后，用消毒棉签擦除上腔残留的细胞，以MTT法测定迁移至膜底面的细胞数目。
表2有效提取物三七原人参二醇型皂苷对VEGF诱导的内皮细胞迁移的影响
| 组别 | 550nm比色值 | 抑制率 |
| 溶剂对照组DMSO有效提取物三七原人参二醇型皂苷10μg/ml | 0.654±0.0890.432±0.078** | 33.9％ |
| 有效提取物三七原人参二醇型皂苷50μg/ml | 0.234±0.102** | 64.2％ |
**与对照组相比，P＜0.01
三.有效提取物三七原人参二醇型皂苷对人类肿瘤细胞生长的影响
人乳腺癌肿瘤细胞MCF-7、肝癌细胞HepG2、口腔上皮癌细胞KB接种至96孔板，每孔5000细胞。培养24h后，分别设对照组，含等量的溶剂DMSO0.2％；阳性药物组5μg/ml盐酸阿霉素；以及不同浓度(12.5～200μg/ml)的有效提取物三七原人参二醇型皂苷。培养24h后，以MTT法进行测定，以490nm比色值反映细胞数量和活力。
实验表明，阿霉素对肿瘤细胞的生长具有明显抑制作用，对MCF-7、HepG2、KB抑制率分别为42.1％、33.4％和57.5％。而有效提取物三七原人参二醇型皂苷在100μg/ml浓度以下，未显示明显的抑制细胞生长效果，近在200μg/ml浓度下显示不超过30％的抑制效果。说明有效提取物三七原人参二醇型皂苷没有直接抑制肿瘤细胞生长或细胞毒作用。
四.有效提取物三七原人参二醇型皂苷对小鼠移植性肿瘤S180的抑制作用
40只ICR雄性小鼠，体重20±2g，腋下接种小鼠肉瘤所S180。饲养48h后，分为四组，每组10只。荷瘤对照组，每目灌胃给予生理盐水；阳性药对照组，环磷酰氨(CTX)30mg/kg隔日腹腔注射给药；三七二醇皂苷低剂量组25mg/kg每日灌胃给药；三七二醇皂苷高剂量组50mg/kg每日灌胃给药。连续给药8天，脱颈处死动物，解剖动物，分离取腋下肉瘤，称重。
表3有效提取物三七原人参二醇型皂苷对小鼠移植性肿瘤S180的抑制作用
| 组别 | 瘤重(g) | 抑制率 |
| 荷瘤对照组环磷酰氨对照组有效提取物三七原人参二醇型皂苷25mg/kg | 1.234±0.3 860.701±0.583*0.745±0.168* | 43.2％39.6％ |
| 有效提取物三七原人参二醇型皂苷50mg/kg | 0.649±0.206* | 47.4％ |
**与荷瘤对照组相比，P＜0.01；*与荷瘤对照组相比，P＜0.05
实验表明，有效提取物三七原人参二醇型皂苷对小鼠移植性肿瘤的生长具有显著的抑制作用。
Claims (6)
1.一种三七原人参二醇型皂苷制备方法，其特征是通过以下步骤制备：
(1)用含水乙醇作为溶剂对三七进行提取，
(2)提取液经过色谱柱层析得洗脱液，
(3)用反相液相色谱梯度洗脱，收集洗脱液经浓缩得到目的提取物；具体是将三七药材粉碎至3mm-8mm颗粒状，70％乙醇10倍溶剂量提取2次，每次2小时，提取液浓缩至1g生药/ml，上大孔树脂D101，先用水冲洗3-5个柱体积，，再用0.05-0.1％氨水冲洗4-5BV，再用水冲洗至pH＝7，再用40％乙醇冲洗3柱体积，最后用70％乙醇洗脱3-5柱体积，收集70％乙醇洗脱液，浓缩，干燥，将样品以水溶解，上反相填料柱ODS C18先以20-25％乙醇洗脱3-4柱体积，再以40-50％乙醇洗脱3-5柱体积，收集洗脱液，回收溶剂，干燥，以水溶解后上大孔树脂D101，分别以30％，70％乙醇洗脱3柱体积，收集70％乙醇洗脱液干燥后得到目的提取物，该提取物为主要含有达玛烷型四环三萜类原人参二醇型皂苷类提取物，其活性组成人参皂苷Rb1和Rd在提取物中含量不低于60％，提取物中还含原人参三醇型皂苷，其人参皂苷Re、Rg1和三七皂苷R1总含量不高于5％。
2.根据权利要求1所述的三七原人参二醇型皂苷制备方法获得的提取物在制备治疗恶性实体瘤的药物中应用。
3.权利要求书2所述的三七原人参二醇型皂苷制备方法获得的提取物的应用，其特征是：所制备的药物还含有制剂允许的药物赋形剂或载体。
4.根据权利要求2所述的三七原人参二醇型皂苷制备方法获得的提取物的应用，其特征是：所制备的药物还含有其他抗肿瘤药物。
5.根据权利要求2所述的三七原人参二醇型皂苷制备方法获得的提取物的应用，其特征是：所述药物的制剂形式为液体制剂、固体制剂、胶囊剂或胶丸剂。
6.根据权利要求5所述的三七原人参二醇型皂苷制备方法获得的提取物的应用，其特征是：所述药物的给药方式为口服给药或注射给药。
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| CN101829170A (zh) * | 2010-05-13 | 2010-09-15 | 北京中海康医药科技发展有限公司 | 一种三七总皂苷提取物及其制备方法 |
| CN102727508A (zh) * | 2012-07-15 | 2012-10-17 | 浙江大学 | 人参二醇皂苷组分制备及在防治帕金森氏病中的药物用途 |
| CN105055514A (zh) * | 2015-08-19 | 2015-11-18 | 成都华神集团股份有限公司 | 一种中药组合物及其制备方法和应用 |
| CN110156863A (zh) * | 2018-02-12 | 2019-08-23 | 吉林紫鑫参工堂生物科技有限公司 | 一种人参皂苷Rd自动控制分离纯化方法 |
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| CN100453550C (zh) * | 2005-06-03 | 2009-01-21 | 吉林农业大学 | 人参皂苷Rb2的制备工艺 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101829170A (zh) * | 2010-05-13 | 2010-09-15 | 北京中海康医药科技发展有限公司 | 一种三七总皂苷提取物及其制备方法 |
| CN102727508A (zh) * | 2012-07-15 | 2012-10-17 | 浙江大学 | 人参二醇皂苷组分制备及在防治帕金森氏病中的药物用途 |
| CN105055514A (zh) * | 2015-08-19 | 2015-11-18 | 成都华神集团股份有限公司 | 一种中药组合物及其制备方法和应用 |
| CN105055514B (zh) * | 2015-08-19 | 2019-08-06 | 成都泰合健康科技集团股份有限公司 | 一种中药组合物及其制备方法和应用 |
| CN110156863A (zh) * | 2018-02-12 | 2019-08-23 | 吉林紫鑫参工堂生物科技有限公司 | 一种人参皂苷Rd自动控制分离纯化方法 |
| CN110156863B (zh) * | 2018-02-12 | 2022-12-13 | 吉林紫鑫参工堂生物科技有限公司 | 一种人参皂苷Rd自动控制分离纯化方法 |
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