CN1265037A - 大豆提取物、其制备方法及其药物组合物 - Google Patents
大豆提取物、其制备方法及其药物组合物 Download PDFInfo
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- CN1265037A CN1265037A CN98807664A CN98807664A CN1265037A CN 1265037 A CN1265037 A CN 1265037A CN 98807664 A CN98807664 A CN 98807664A CN 98807664 A CN98807664 A CN 98807664A CN 1265037 A CN1265037 A CN 1265037A
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- extract
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- isoflavone
- soyasaponins
- ethanol
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Abstract
本发明涉及具有特定大豆皂甙和异黄酮苷比的新的大豆提取物;其制备方法以及含有这些提取物的药物组合物。
Description
本发明涉及通过提取成熟的全大豆或不含油的大豆粉(G1ycine max(L.)MERRIL,豆科)得到的新的提取物、其生产方法以及含有这些提取物的制剂。该新的提取物的特征在于其异黄酮和皂甙的含量具有特定的比例。
已知大豆除了含有糖和氨基酸成分之外还含有皂甙和异黄酮成分,以及蛋白质和无机盐,这些成分的含量取决于大豆的地理学产地以及植物的种植和收获条件。
根据其三萜成分的化学结构,皂甙被分成三类:A、B和E组的大豆皂甙(Okubo K.等,ACS Symp.,Ser.546,330,1994)。
R1 R2 R3A组 糖链 糖链 OHB组 糖链 OH HE组 糖链 -O H
R1 R2 R3黄豆苷 H H D-葡萄糖黄豆黄素苷 OCH3 H D-葡萄糖染料木苷 H OH D-葡萄糖黄豆苷原 H H H黄豆黄素 OCH3 H H染料木素 H OH H
根据最近几年出版的生物医学文献和流行病学资料(主要涉及东方的人群,这些人群食用以大豆为原料的食品的量很大),食用这些食物可以很大程度地减少妇女的绝经前和绝经后的症状(A.Cassidy,营养学进展(Proceedings of the Nutrition Society),1996,55,339-417)。这些事实目前仍缺乏确切的科学基础,但通常归因于异黄酮糖苷配基染料木素、黄豆苷原和黄豆黄素,它们存在于各种以大豆为原料的食品中。
异黄酮通常被认为是植物雌激素,大量的体外研究表明这些物质以与哺乳动物雌激素竞争的机制产生作用,其活性比雌二醇低500-1000倍(D.A.Shutt和R.I.Cox,内分泌学杂志(Journal of Endocrinology),1972,52,299-310)。
根据最近几年出版的其它生物医学文献和流行病学资料(主要涉及东方的人群,这些人群食用以大豆为原料的食品的量很大),使用这些食物可以很大程度地减少妇女乳腺癌和男性的前列腺癌(A.Nomura,B.E.,Henderson J.Lee,美国临床营养学杂志(American Journal ofClinical Nutrition),1978,31,2020-2025,T.Hirayama,饮食、营养和癌症(Diet,Nutrition and Cancer).1986,41-53页,Y.Hayashi,M.Nagao,T.Sugimura,S.Takayama,L.Tomatis,L.W.Wattenberg和G.N.Wogan编,东京:日本科学协会出版社;R.K.Severson,A.M.Y.Nomura,J.S.Grove,G.N.Stemmerman,癌症研究(Cancer Research),1989,49,1857-1860)。同样,虽然这些事实目前仍缺乏确切的科学基础,但通常归因于异黄酮糖苷配基染料木素、黄豆苷原和黄豆黄素,它们存在于各种以大豆为原料的食品中。
在体外模型中研究了这些异黄酮类化合物与蛋白激酶、特别是酪氨酸激酶(可能在肿瘤细胞的增殖中起作用的酶)相互作用的能力。
最近进行了大量的尝试,以制备用于预防性治疗绝经前和绝经后症状以及用于预防性治疗癌症的以大豆提取物为基础的药物。一些专利或专利申请描述了通过化学或酶水解大豆或大豆苗中的异黄酮苷得到的新的大豆提取物的组合物(Kikkoman Corp.J-08291191,KikkomanCorp.J-07173148,Kelly GE WO-9323069,Kikkoman Corp.J-051707566)。所有这些出版物均仅涉及高浓度并且具有控制绝经前和绝经后疾病活性以及抗肿瘤活性的异黄酮的制备。
现已发现,与以前的公开内容相反,含有特定比例的异黄酮苷和B组大豆皂甙的提取物在预防或治疗绝经前和绝经后症状以及预防或治疗癌症方面均比异黄酮本身更为有效。
本发明提取物的另一方面涉及滥用酒精和酒精依赖或酒精成瘾。这些现象可以统称为“酗酒”,它已成为整个现代社会的一个严重问题(Gessa G.L.,“强迫饮酒和快乐原则”,Medicina delletossicodipendenze[药物依赖医学]II,5(1994))。例如,在意大利,9%以上的人群(约5百万)严重酗酒,并且有1百万以上是酒精依赖的(Calamo-Spechhia F.P.,“意大利的酗酒流行病学”,Atti del VIIcongresso Nazionale della S.I.A.[第7届S.I.A.国民代表大会报告]Mediserve,罗马,295-301(1991))。当将美国等国家考虑在内时,这些数字将会增加,在美国,有1300万以上是酒精依赖的。酒精滥用和酒精依赖会导致非常高的财政开支(自从1991年以来,美国每年花费约2000亿美元)并且会造成严重的社会问题以及对受影响者的心理损伤。
除了心理上的治疗(例如团体疗法)外,目前用于治疗酗酒的方法包括施用药物如双硫仑和尿素钙,这些药物可以作用于酒精代谢,抑制肝脏的乙醛脱氢酶,从而增加具有摧吐作用的乙醛水平的增加,并且抑制在酒精摄入过程中出现的各种不希望的现象。
在现有技术中,将其衍生物用于治疗酗酒的仅有的植物是野葛(葛根)和丹参,这些植物在中药中的应用非常广泛,并且是专利申请WO93/00896和WO96/35441的主题。除了提取物的用途外,这些专利申请还要求保护纯净物质如黄豆苷原及其半合成衍生物(WO93/00896)或双萜类如丹参酮和丹参新酮(WO96/35441)的用途。已公开了异黄酮衍生物对乙醇脱氢酶的影响以及出现的上述副作用,而同样的机制已被从双萜类化合物中排除。此外,专利申请WO96/36332公开了福斯高林在减少乙醇消化中的作用。
令人惊奇的是,现已发现含有特定比例的异黄酮苷和B组大豆皂甙的提取物可有效地减少蓄意的酒精消耗。这些提取物明显比单独使用异黄酮更为有效,并且是通过不同于抑制乙醇脱氢酶的机制起作用,因为乙醇的血浆水平保持不变。
除上述现有技术外,WO96/10341公开了含有基本纯净的大豆种子胚轴的食品或保健品。其中没有提到提取方法以及本发明所述的异黄酮和皂甙之间的比例。
US4428876公开了从豆科植物中分离皂甙和黄酮的方法。其中所公开的用0.4%氢氧化钠水溶液提取大豆的方法所得到的最终提取物与本发明的提取物不同。同样,其中也没有提到本发明所述的异黄酮和皂甙之间的比例。
JP59088064仅涉及皂甙的分离和用途。DE3400258也是如此。与此相似,JP61036225涉及皂甙的分离和纯化,JP62005917涉及完全不含异黄酮的纯净皂甙的制备。JP4036242涉及用作抗炎化合物的纯净皂甙或具有高皂甙/异黄酮比的提取物的制备。
EP-A-426998公开了从大豆制备异黄酮、特别是染料木苷和黄豆苷丙二酸酯的方法。其中没有提到皂甙的提取以及异黄酮和皂甙之间的比例。
JP63245648涉及不含皂甙和异黄酮的大豆食品的制备,这些物质被认为是导致食物不能食用的粗糙成分。
Mark Messina等,国家癌症研究所杂志(Journal of the NationalCancer Institute),83卷,1991年,541-546页涉及已在科技文献中报道的大豆产品在减少癌症危险性中的作用。但是,该文献以及其它文献均没有提到含有本发明所述比例的皂甙和异黄酮的提取物,更没有提到该特定的提取物所能产生的药理学作用。
因此,本发明涉及对于每一重量份异黄酮苷,B组大豆皂甙的含量为0.6-1.5重量份、优选1重量份的提取物,提取物中异黄酮苷的含量至少为13%(重量)。
R1 R2大豆皂甙V CH2OH 葡萄糖大豆皂甙II异构体 CH3 阿拉伯糖大豆皂甙I CH2OH 鼠李糖大豆皂甙II H 鼠李糖大豆皂甙III CH2OH H大豆皂甙IV H H
本发明还涉及生产上述提取物的方法,其特征在于包括如下步骤:
a)将成熟的全大豆或不含油的大豆粉用脂肪族醇或这些醇与水的混合物提取;
b)将a)步骤的提取物浓缩;
c)将b)步骤的浓缩提取物用脂肪族烃处理进行纯化,以除去其中的油和亲脂性物质;
d)用与水不相混溶的脂肪族醇提取活性成分;
e)将d)步骤的提取物浓缩并干燥。
具体地讲,本发明的提取物可以通过以下步骤得到:将含有相对比例为3∶2至2∶3的B组大豆皂甙和异黄酮苷的全大豆或不含油的大豆粉用脂肪族醇或这些醇与水的混合物-优选乙醇/水的混合物(如95%的乙醇)提取。浓缩并用脂肪族烃(例如正已烷或正庚烷)处理除去其中的油和亲脂性物质后,将活性成分用与水不相混溶的脂肪族醇如正丁醇、异丁醇和异戊醇提取。浓缩后,将有机相减压干燥。本发明还涉及上述方法的改变形式,其中,在步骤b)或c)之后,将浓缩的乙醇提取物进行如下的步骤d’),然后再进行步骤e):
d’)将活性成分吸附在聚苯乙烯基吸附树脂上;将树脂用水冲洗;用乙醇洗脱活性成分。
根据该改变形式,本发明的典型提取物可以通过如下方式得到:将活性成分(异黄酮和皂甙,它们存在于植物材料的浓缩乙醇提取物中)吸附在聚苯乙烯基吸附树脂例如Duolite或XAD(特别是XAD1180,因其是弱酸性的)上;用水小心地冲洗树脂柱除去盐和其它无活性的成分后,将异黄酮和B组大豆皂甙的混合物用乙醇洗脱。
该条件下得到的提取物含有13-17%(重量)的异黄酮,并且根据所用植物原料的质量,对于每1重量份异黄酮苷,B组大豆皂甙的含量为0.6-1.5重量份。该提取物还含有大量多元酚物质,已证实该物质是提取物的内在活性所必需的。
上述方法及其改变形式的一个实施方案包括如下步骤:
f)将步骤e)的提取物悬浮在与水混溶的醇和水的混合物中并用与水不相混溶的非质子溶剂稀释;
g)将步骤f)的混合物加热使其溶解,然后将其放置在室温下;
h)过滤收集沉淀的B组大豆皂甙;
i)将有机相与水相分离;浓缩有机相并干燥得到异黄酮成分;和
j)将步骤h)的皂甙和步骤i)的异黄酮混合形成提取物。
因此,本发明的提取物还可以从按照上述方法或其改变形式制得的提取物进行生产,即使那些异黄酮苷的含量很高并且B组大豆皂甙具有上述比例的提取物也可以。为此,该方法可按照如下所述进行:将所述提取物悬浮在与水混溶的醇如乙醇或甲醇中,水的含量为10-50%(体积),然后用与水不相混溶的非质子溶剂如二氯甲烷或乙酸乙酯稀释。将得到的多相混合物加热使提取物溶解,然后将其放置在室温下,从而使B组大豆皂甙形成沉淀。过滤收集得到纯度大于90%的皂甙。从含水母液中分出有机相,将有机相蒸发并干燥得到纯度大于80%的异黄酮成分。然后将异黄酮和皂甙混合得到异黄酮苷的含量为最大可能值并且B组大豆皂甙的含量为0.6-1.5重量份每1重量份异黄酮苷的提取物。
完成本发明方法各步骤的优选条件如下。在该情况下,用于计量体积份的单位是1(升),用于计量重量份的单位是kg(千克)。
步骤a:优选将植物原料用12-17体积溶剂/1重量份生物质进行提取。提取温度在55℃以上。每次提取的时间在4小时以内。除乙醇之外的适宜溶剂是,甲醇、丙醇和异丙醇。这些溶剂可以含有最多10%的水。
步骤b:将提取物在低于50℃的温度下减压浓缩。将提取物浓缩至醇含量为65-75%。
步骤c:用0.3-0.6体积脂肪族烃/1重量份植物原料进行纯化。适宜的方法是提取油和亲脂性物质。
步骤d:将活性成分每次用0.2-0.4体积与水不相混溶的醇溶剂/1重量份植物原料进行萃取;优选萃取3次。
步骤e:将步骤d的提取物在低于50℃的温度下减压浓缩。
步骤f:将步骤e)的提取物悬浮在5-10体积(每1份提取物)水-可溶性醇中,醇/水的比例为2∶8-3∶7(体积/体积)。与水不相混溶的非质子溶剂的用量为2-5体积,以1重量份步骤e的提取物计。
步骤g:为了能够完全溶解,将混合物加热回流。然后优选将混合物保持在室温下15-24小时。
步骤i:将有机相在低于30℃的温度下减压蒸发进行浓缩。
步骤j:优选用步骤h的皂甙和步骤g的异黄酮苷制备含有皂甙和异黄酮苷的比为1∶1的醇溶液,然后将该溶液在低于50℃的温度下浓缩至干。
异黄酮和B组大豆皂甙的含量通过HPLC分析测定:Supelco-SilLC-ABZ柱(250mm×4.6mm),5μm,三元洗脱液梯度洗脱,包括A)H2O(CF3COOH 0.01%),B)乙腈(CF3COOH 0.01%)和C)甲醇(CF3COOH 0.01%)。各组分可以通过质谱和HPLC联用采用热喷雾界面进行鉴定。
本发明的提取物在其独特的作用方面不同于目前已知的提取物。就绝经疾病而言,热潮红、失眠和抑郁是绝经妇女最常见的更年期症状。这些症状伴有卵巢活性的减弱或中断,从而使雌激素的产生减少,促黄体生成激素(LH)和卵泡刺激激素(FSH)的产生增加。
最近的研究(Duker E.M.等,Planta.Med.57,420,1991)报道了卵巢切除术后雌性大鼠LH的临时增加与皮肤温度改变之间的联系。LH水平与热潮红之间的这种联系(在雌性大鼠和妇女中均观察到了这种联系)表明分泌的LH剂量可以作为研究活性内分泌化合物的精神神经病/内分泌作用的适宜参数。
表1给出了将切除卵巢的雌性大鼠用两种单独的成份(异黄酮和B组大豆皂甙)以及本发明的提取物处理所得到的结果。表1:将大豆提取物口服给药后切除卵巢的雌性大鼠的血浆促黄体生成
激素(LH)浓度
给药的产品 剂量(mg/kg/天) LH(ng/ml)载体 10ml/kg 6.2±0.01B组大豆皂甙 1000 5.8±0.02大豆异黄酮 1000 3.4±0.001实施例1制得的大豆提取物 1000 2.1±0.001实施例3制得的大豆提取物 1000 1.3±0.001
用已知的方法对雌性大鼠进行卵巢切除术。手术15天后,将动物用试验物质进行处理,每天口服给药一次,共15天。最后一次给药3小时后处死动物。然后将血液立即进行离心,将得到的血清保存在-25℃下直至按照Miswender等的方法(Proc.Soc.Exp.Biol.Med.128,807,1986)通过放射免疫分析测定LH。
可以看到,给药本发明的提取物可以使LH产生具有统计学意义的减少,其减少程度大于使用各成分时得到的总和(协同作用)。
将提取物用于对健康动物反复处理时,对雄性动物不会引起器官或系统发生肉眼可见的或用显微镜可见的改变,而在雌性动物中,它们可以改变子宫和骨骼的重量,这证实了它们的雌激素活性。
当将本发明的提取物对绝经期的妇女-不论绝经是自然发生的还是由于手术引起的-进行给药时,它们可以在给药数天内改变血浆LH水平并减少绝经疾病如热潮红或抑郁等,并且在长期治疗时还可减少骨的脱矿质。
本发明的提取物还具有明显的抗增殖活性。表2给出了对卵巢肿瘤细胞系(OVCA433)的抗增殖活性。表2:大豆提取物对卵巢肿瘤细胞系(OVCA433)的体外抗增殖活性
化合物 | IC50μm |
B组大豆皂甙 | 6.2 |
大豆异黄酮 | 4.5 |
实施例1制得的大豆提取物 | 1.6 |
实施例3制得的大豆提取物 | 1.1 |
将细胞在最低基础培养基上进行单层培养,所述培养基中含有牛血清,并且含有200单位/ml的青霉素以保持培养基的无菌。为了试验的可重复性,将细胞每周用胰蛋白酶处理并以8×104细胞/ml的密度涂覆在平板上,然后在含有5%CO2的潮湿空气下于37℃保温。为了分析化合物的活性,将细胞用最少量的底物以1×105/ml的浓度置于孔中(Falcon 3046,Becton Dickinson NY)。24小时后,将底物用新鲜的底物替换并加入溶于无水乙醇的化合物。对照按照类似的方式用不含试验化合物的赋形剂处理。以24的间隔重复上述处理过程,试验期为72小时。通过直接计算细胞来评估对细胞增殖的抑制作用,用对照细胞的生长与“处理”细胞的生长进行比较。结果表明,本发明的提取物所具有的抗增殖活性大于其组分的抗增殖活性的总和(协同作用)。通过测定按照文献中报道的常规条件移植到无胸腺裸鼠体内的肿瘤体积证实了本发明的化合物可以在体内抑制细胞增殖。将动物用10-500mg/kg的剂量处理可以导致所研究的肿瘤明显退化,在大部分个体中,肿瘤消失。
关于对酒精消耗的抑制作用,用“Sardinian嗜酒”(Sp)品种的食用酒精的大鼠(Fadda F.,Mosca E.,Colombo G.,Gessa G.L,嗜酒大鼠;对酒精引起的多巴胺代谢刺激作用的遗传敏感性,Physiol.Behav.47,727(1990))测定了其作用。这些动物在可以自由地选择酒精和水时,每天消耗6-7g酒精/公斤体重(水与酒精的比大于2∶1),近年来,这些动物已成功地用于测定各种物质对自愿酒精消耗的影响,参见,例如,Balakleevsky A.,Colombo G.,Fadda F.,Gessa G.L.,Ro 19-4603,苯并二氮杂受体反激动剂,在选择性喂养的对酒精非常嗜好的大鼠中减弱乙醇消耗,Alcohol Alcohol 25,449-542(1990),Fadda F.,Garau B.,Colombo G.,Gessa G.L.,伊拉地平和其它钙通道拮抗剂减弱嗜酒大鼠的乙醇消耗,酗酒:临床和实验研究(Alcoholism:Clinical and Exerimental Research)16(3),449-452(1992)。
动物保持在正常的喂养条件下并且可以自由地在水(一直提供)和酒精(浓度10%的溶液,体积/体积)之间进行选择,乙醇在每天4小时的期间内(即白天/黑夜循环的前4个小时的黑暗期间内)提供。每天在同一时间记录消耗的水和乙醇的量。食物可自由接近。在达到稳定的乙醇和水消耗量后,将提取物以1000mg/kg水混悬液的剂量口服给药,给药体积为2ml/kg,每天给药1次,连续给药7天。对照使用相同体积的赋形剂。处理结束时,记录乙醇的消耗量直至达到处理前的数值。
表3给出了重复口服给药1000mg/kg大豆提取物对乙醇消耗的影响。
表3.重复口服给药大豆提取物对Sp(Sardinian嗜酒)
乙醇消耗的影响。化合物 剂量 乙醇消耗量(g/kg)
(mg/kg)
第一天 第二天 第三天 第四天 第五天 第六天 第七天 第八天 第九天 第十天载体 2ml/kg 2.9±0.1 2.9±0.2 2.8±0.3 2.9±0.2 2.6±0.2 3.0±0.1 2.9±0.3 2.9±0.1 2.8±0.2 2.6±0.2B组大豆皂甙 1000 2.8±0.1 2.8±0.3 2.9±0.2 2.7±0.3 2.2*±0.1 2.2*±0.1 2.6±0.2 2.7±0.2 2.9±0.1 3.0±0.2大豆异黄酮 1000 2.6±0.2 2.9±0.2 2.8±0.1 2.9±0.3 1.9*±0.2 1.9*±0.2 2.0*±0.1 1.9*±0.1 2.3±0.2 2.6±0.3按照实施例1 1000 3.0±.2 2.9±0.1 2.9±0.3 2.0*±0.1 1.8*±0.1 1.6**±0.1 1.4**±0.2 1.5**±0.1 2.0±0.2 2.4±0.3生产的大豆提取物按照实施例3 1000 2.8±0.2 2.9±0.3 3.0±0.3 2.1*±0.1 1.6**±0.1 1.7**±0.1 1.2**±0.2 1.2**±0.1 1.9*±0.2 2.2±0.3生产的大豆提取物
*p<0.05,**p<0.01,
与载体处理的动物多重比较的Dunnet’s t-试验
从表3可以得出结论:大豆提取物可以明显减少乙醇的消耗。在7天的治疗期间内,乙醇的消耗持续减少,在治疗结束后该作用减弱。此外,可以发现,乙醇消耗量的减少大于各成分作用的总和(协同作用)。
因此,本发明还涉及含有上述提取物作为活性成分的药物组合物。具体地讲,本发明涉及含有该提取物的用于预防或治疗绝经前和绝经后症状的药物组合物、含有该提取物的用于预防和治疗妇女乳腺癌和男性前列腺癌的药物组合物以及含有该提取物的用于预防或治疗酗酒的药物组合物。
本发明的产品或提取物可以通过适宜的方式配制成片剂、软或硬明胶胶囊、用于制备与其溶解度相适应的即用溶液或液体的颗粒状粉末。本发明提取物的剂量在30mg-500mg的范围内,可以每日给药1次或多次,优选200mg,每日给药两次。适宜的给药剂型是口服剂型。
以下实施例用来说明本发明。实施例1-通过用溶剂纯化生产异黄酮含量为15%(重量)、异黄酮苷/B组大豆皂甙的比为1∶1.5的大豆提取物
将10kg不含油的大豆粉用30升95%的乙醇回流5次,所述大豆粉含有0.22%异黄酮苷和0.3%B组大豆皂甙。将乙醇提取物混合并减压浓缩成5升。将浓缩物用1.5升水稀释并用5升正己烷提取4次。弃除己烷相并将浓缩的乙醇相用2.5升正丁醇提取4次。将有机相减压浓缩并干燥。得到133g异黄酮含量为15%(重量)、B组大豆皂甙的含量为22.5%(重量)的提取物。
由该实施例的方法所得到的提取物的HPLC图如图1所示。实施例2-通过在聚苯乙烯树脂上纯化生产异黄酮含量为15%(重量)、异黄酮苷/B组大豆皂甙的比为1∶1.5的大豆提取物
将实施例1制得的含水浓缩物不用正丁醇提取,而是用聚乙氧基化的蓖麻油(Cremophor)处理,以溶解浓缩乙醇相时产生的树脂状残余物。然后将其悬浮在纯净水(5升)中并上到XAD1180树脂柱上。将柱子用水冲洗以完全除去盐、糖和表面活性剂,然后用约10升95%的乙醇洗脱。将乙醇洗脱液浓缩并干燥后,得到130g与实施例1所得提取物组成相同的提取物。实施例3-异黄酮含量为43%(重量)、异黄酮苷/B组大豆皂甙的比为1∶1的大豆提取物的生产
将200g实施例1或2得到的提取物悬浮在1升20%乙醇水溶液中并用0.5升乙酸乙酯稀释。将该悬浮液在剧烈搅拌下加热直至完全溶解,然后放置过夜。过滤分离析出的皂甙沉淀(38g,纯度93%),并分出含有乙酸乙酯和水的含水母液。将有机相减压浓缩并干燥。将异黄酮残余物(37g,纯度81%)溶于1升乙醇并与32g结晶皂甙混合以得到异黄酮和皂甙的重量比1∶1的产物。将乙醇溶液减压浓缩至干得到69g异黄酮苷的含量为43%(重量)、B组大豆皂甙的含量为43%(重量)的提取物。实施例4-含有大豆提取物的硬明胶胶囊的生产按照实施例1制得的大豆提取物 200.0mg乳糖 67.5mg微晶纤维素 22.5mg胶态二氧化硅 3.0mg交联羧甲基纤维素钠(羧甲基纤维素钠的交联聚合物) 21.0mg滑 8.0mg硬脂酸镁 3.0mg实施例5-含有大豆提取物的片剂的生产按照实施例3制得的大豆提取物 400.0mg大豆多糖 155.5mg微晶纤维素 57.0mg羟丙甲基纤维素 12.0mg氢化植物油 19.5mg胶态二氧化硅 3.0mg硬脂酸镁 3.0mg
Claims (11)
1.大豆提取物,其特征在于,对于每一重量份异黄酮苷,B组大豆皂甙的含量为0.6-1.5重量份,提取物中异黄酮苷的含量至少为13%(重量)。
2.权利要求1的大豆提取物,其特征在于,对于每一重量份异黄酮苷,B组大豆皂甙的含量为1重量份。
3.生产权利要求1或2所述提取物的方法,其特征在于包括如下步骤:
a)将成熟的全大豆或不含油的大豆粉用脂肪族醇或这些醇与水的混合物提取;
b)将a)步骤的提取物浓缩;
c)将b)步骤的浓缩提取物用脂肪族烃处理进行纯化,以除去其中的油和亲脂性物质;
d)用与水不相混溶的脂肪族醇提取活性成分;
e)将d)步骤的提取物浓缩并干燥。
4.权利要求3所述方法的改变形式,其中,在步骤b)或c)之后,将浓缩的乙醇提取物进行如下的步骤d’),然后再进行步骤e):
d’)将活性成分吸附在基于聚苯乙烯的吸附树脂上;将树脂用水冲洗;用乙醇洗脱活性成分。
5.权利要求3或4的方法,还包括如下附加步骤:
f)将步骤e)的提取物悬浮在与水混溶的醇和水的混合物中,并用与水不相混溶的非质子溶剂稀释;
g)将步骤f)的混合物加热使其溶解,然后将其放置在室温下;
h)过滤收集沉淀的B组大豆皂甙;
i)将有机相与水相分离;浓缩有机相并干燥得到异黄酮成分;和
j)将步骤h)的皂甙和步骤i)的异黄酮混合形成提取物。
6.一种药物组合物,含有权利要求1或2所述提取物作为活性成分。
7.权利要求6所述的药物组合物,用于预防或治疗绝经前和绝经后症状。
8.权利要求6所述的药物组合物,用于预防或治疗癌症。
9.权利要求6或8所述的药物组合物,用于预防或治疗妇女乳腺癌。
10.权利要求6或8所述的药物组合物,用于预防或治疗男性前列腺癌。
11.权利要求6所述的药物组合物,用于预防或治疗酗酒。
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1998
- 1998-07-30 EP EP98942659A patent/EP1001797B9/en not_active Expired - Lifetime
- 1998-07-30 WO PCT/EP1998/004770 patent/WO1999006057A1/en active IP Right Grant
- 1998-07-30 AT AT98942659T patent/ATE297213T1/de active
- 1998-07-30 CN CN98807664A patent/CN1089245C/zh not_active Expired - Fee Related
- 1998-07-30 AU AU90711/98A patent/AU740356B2/en not_active Ceased
- 1998-07-30 PT PT98942659T patent/PT1001797E/pt unknown
- 1998-07-30 HU HU0003058A patent/HU229444B1/hu not_active IP Right Cessation
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- 1998-07-30 ES ES98942659T patent/ES2243005T3/es not_active Expired - Lifetime
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- 1998-07-30 SK SK104-2000A patent/SK283491B6/sk not_active IP Right Cessation
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- 1998-07-30 DK DK98942659T patent/DK1001797T3/da active
- 1998-07-30 RU RU2000105259/14A patent/RU2183964C2/ru not_active IP Right Cessation
- 1998-07-30 PL PL337520A patent/PL191191B1/pl unknown
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2000
- 2000-01-26 NO NO20000399A patent/NO323231B1/no not_active IP Right Cessation
- 2000-01-28 US US09/492,921 patent/US6280777B1/en not_active Expired - Lifetime
- 2000-07-04 HK HK00104037A patent/HK1025507A1/xx not_active IP Right Cessation
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2001
- 2001-07-11 US US09/902,226 patent/US6607757B2/en not_active Expired - Lifetime
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2002
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CN100345505C (zh) * | 2004-12-21 | 2007-10-31 | 山东理工大学 | 提取大豆异黄酮、皂甙、低聚糖的挤压加工方法和装置 |
CN101477098B (zh) * | 2009-01-08 | 2012-07-18 | 上海交通大学 | 利用大豆天然提取物检测大豆抗蚜性的方法 |
CN102548565A (zh) * | 2009-10-22 | 2012-07-04 | 株式会社益力多本社 | 癌症发病风险降低剂 |
US8778332B2 (en) | 2009-10-22 | 2014-07-15 | Kabushiki Kaisha Yakult Honsha | Agent for reducing risk of developing cancer |
CN106890198A (zh) * | 2009-10-22 | 2017-06-27 | 株式会社益力多本社 | 癌症发病风险降低剂 |
CN106028795A (zh) * | 2013-12-13 | 2016-10-12 | 庆尚大学校产学协力团 | 具有高含量异黄酮衍生物的豆叶或豆茎及其制备方法 |
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