CN103933188B - 一种抑制肿瘤细胞增殖的中药组合物、制备方法及用途 - Google Patents
一种抑制肿瘤细胞增殖的中药组合物、制备方法及用途 Download PDFInfo
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Abstract
本发明涉及中医药领域,公开了一种抑制肿瘤细胞增殖的中药组合物、制备方法与用途。本发明所述中药组合物由桃仁6.5-8.0重量份、红天葵5.0-8.5重量份、葡萄柚5.0-10.0重量份、甜橙5.5-8.5重量份、桑椹3.5-8.0重量份、杏鲍菇3.5-5.0重量份、广枣5.0-10.0重量份、芒果4.0-6.0重量份、毛冬瓜5.0-8.0重量份、越橘6.0-8.0重量份、银耳5.0-6.5重量份、龙眼5.5-8.5重量份制成。体外实验MYr法和集落形成法结果显示本发明所述中药制剂对多种肿瘤细胞株生长有显著的抑制作用,提示本发明所述中药组合物用作肿瘤治疗药物具有广泛的临床应用前景。
Description
技术领域
本发明涉及一种中药领域,具体涉及一种抑制肿瘤细胞增殖的中药组合物、制备方法与用途。
背景技术
***是最常见的妇科恶性肿瘤,原位癌高发年龄为30~35岁,***为45~55岁,近年来其发病有年轻化的趋势。中国是***病例较多的国家,每年有***新发病例,在女性特有的肿瘤当中,前十位恶性肿瘤中第二位就是***。
目前子***的治疗主要包括手术治疗、放化疗、化疗三种方法。手术治疗手术主要用于早期***患者,可以很大程度改善症状,但对身体的损害很大,且易带来术后不育及肿瘤复发、转移的并发症。
临床还通过放射介入方法治疗***,直接将动脉导管插至子宫动脉,注入永久性栓塞颗粒,阻断子宫肌瘤血供,以达到肌瘤萎缩甚至消失。
药物治疗临床上常用的***释放激素激动剂GnRH-a、孕激素拮抗剂、雄激素类药物。GnRH-a有亮丙瑞林(抑那通)、戈舍瑞林(诺雷德)、曲普瑞林(达必佳)等。GnRH-a不宜长期持续使用,一般用3-6个月,常引起严重更年期症状;孕激素拮抗剂米非司酮近年来临床上用以治疗子宫肌瘤,可使肌瘤体积缩小,但停药后肌瘤多再长大。雄激素类药物常用药物有***(甲基***)和丙酸睾素(丙酸***),可抑制肌瘤生长,常引起男性化。
***目前尚无十分理想的治疗药物,近年来,从天然植物中寻找新的抗肿瘤药物已成为新药研究的主要发展方向之一,中医药在肿瘤治疗中的地位和综合优势愈显重要。目前,已公开的中药(欧美国家称植物药)有如专利号CN102145030B具有调节免疫抑制肿瘤作用的奇异果软胶囊的制备方法以及专利号CN102225182B公开的一种抑制肿瘤及增强免疫力的中药制剂及制备方法。这些中药***疗效欠佳,均不具备在临床广泛应用的前景。
发明内容
本发明的一个目的是针对上述不足,提供一种抑制肿瘤细胞增殖的中药组合物。
本发明提供的一种抑制肿瘤细胞增殖的中药组合物,由以下原料制成:桃仁6.5-8.0重量份、红天葵5.0-8.5重量份、葡萄柚5.0-10.0重量份、甜橙5.5-8.5重量份、桑椹3.5-8.0重量份、杏鲍菇3.5-5.0重量份、广枣5.0-10.0重量份、芒果4.0-6.0重量份、毛冬瓜5.0-8.0重量份、越橘6.0-8.0重量份、银耳5.0-6.5重量份、龙眼5.5-8.5重量份。
桃仁是蔷薇科植物桃或山桃的种子,别名毛桃仁、扁桃仁、大桃仁,6~7月果实成熟时采摘,除去果肉及核壳的种子,有活血祛瘀、润肠通便的功效,可用于经闭、痛经、跌扑损伤、肠燥便秘等。
红天葵(学名:Begonia fimbristipula)又名紫背天葵、红叶、散血子、龙虎叶、夜渡红、红水葵,为秋海棠科植物紫背天葵的球茎或全株。功用主治清热凉血,活血解毒。性味甘涩,凉,无毒。
广枣为漆树科植物南酸枣Choerospondias axillaris(Roxb.)Burtt etHill的干燥成熟果实。主要成分:没食子酸,原儿茶酸,多糖。功能主治;增强免疫,抗肿瘤,行气活血化瘀,养心,安神,抗心肌缺血,保护心功能等作用。用于气滞血瘀,胸痹作痛,心悸气短,心神不安。清热毒,治风毒起疙瘩成疮或疡痛。
毛冬瓜:别名白洋桃、白毛桃、白葡萄、生毛藤梨,为生毛藤梨猕猴桃科猕猴桃属植物毛花杨桃Actinidia eriantha Benth.A.davidii Franch.,中药化学成分:根含胡萝卜甙(dauasierol),熊果酸(ursolicacid),β-谷舀醇(β-sitcoterol),毛花猕猴桃酸(eriantic acid)A、B。功效与作用:抗癌,消肿解毒。根:用于胃癌、乳癌、食道癌、腹股沟***炎、疮疖、皮炎。根皮:外用治跌打损伤。叶:外用治乳腺炎。清热利湿,活血消肿,解毒。治肺热失音,淋浊,带下,颜面丹毒,***炎,皮炎,痈疮肿毒。
葡萄柚(Grapefruit,Pomelo)是芸香科柑橘属植物,学名为Citrus paradis,别名:西柚、血橙等等。化学组分:醇类--牻牛儿醇、芫荽油醇醛类--柠檬醛萜烟--柠檬烯、松油萜。胡萝卜素,维生素B1、维生素B2、维生素C,烟酸、钙、磷、铁、糖类等。药用价值:中医认为葡萄柚性味甘、酸、凉,具有增进食欲,利尿,美白,强化肝功能,减肥,增强记忆力等功效;用于偏头痛,耳聋,胆结石,抗蜂窝组织炎,***等症。
甜橙、别名:黄果、橙子、新会橙广橘、雪柑、印子柑、广柑。英文名:fruit of Sweet Orange,药材基源:为芸香科植物甜橙的果实。拉丁植物动物矿物名:Citrus sinensis(L.)Osbeck,中药化学成分:维生素C、P及有机酸,异樱花素-7-芦丁糖甙、柚皮素-4'-葡萄糖甙-7-芦丁糖甙、柚皮甙、柠檬素-3-β-P-葡萄糖甙和O-D-木糖基牡荆素。内酯中有双内酯苦味成分柠檬苦素即黄柏内酯及其衍生物柠檬苦素酸单内酯。功能主治:疏肝行气、散结能乳、解酒。主肝气郁滞所致胁肋疼痛;脘腹胀满;产妇乳汁不通;***结块肿痛;治妇人乳结不通,红肿结硬疼痛,恶寒发热。对人体新陈代谢有明显调节和抑制作用,可增强机体抵抗力。
越橘,Vaccinium angustifolium,为杜鹃花科越桔属植物,以叶、果入药。中药化学成分:含熊果甙(arbutin),熊果酸(ursolic acid)[1],原花青素(procyanidin)B-1,B-3,B-7,原花色素(proanthocyanidin)A、果酸、维生素C,功用:有增强心脏功能,预防癌症和心脏病的功效,能防止脑神经衰老、增进脑力;对一般的伤风感冒,咽喉疼痛以及腹泻也有一定改善作用,消炎,防腐。
葡萄柚、甜橙、桑椹、杏鲍菇、广枣、芒果、毛冬瓜、越橘、银耳、龙眼均为常用的食材。中医认为妇科、乳腺疾病因脏腑功能失调、气滞血瘀而成。本发明所述中药组合物治疗妇科、乳腺疾病,多以活血化瘀、消瘀散结、清热解毒、疏肝理气、化瘀止痛为主,能改善增生的子宫内膜的血液循环,使肌层的单纯性肥大逐渐消失,增生的******,从而起到调经、止血、疼痛消失、恢复卵巢功能的治疗作用,能有效地控制子宫颈囊肿生长,使瘤体逐渐软化,最后消散。
本发明所述抑制肿瘤细胞增殖的中药组合物针对***的中医治疗,以辨证论治为原则,内服并配合宫颈局部外用,体现中医药综合治疗优势,能够抗癌抑瘤,改善临床症状、提高生活质量,调节免疫功能。
本发明制成的中药组合物有效成分含量高,比传统工艺提高工效,质量得到了保障、提高了安全用药率。本发明提供的中药组合物经分析测定,其主要成分包含金丝桃苷、植物总多酚、氨基酸、维生素A、C和B族维生素类、儿茶素成分等。金丝桃苷具有抗炎、解痉、利尿、止咳、降压、降低胆固醇以及对心、脑血管的保护作用等多种生理活性,可活血化瘀,用于瘀血闭阻所致的血脉瘀阴症者。经药效学研究表明,其药物有效成份含量明确,并得到最大程度保留,有效成份含量的检测方法科学、准确率高,从而提高了药物的利用度。
作为优选,本发明所述中药组合物由以下原料制成:桃仁7-8.0重量份、红天葵6..0-8.0重量份、葡萄柚6.0-9.0重量份、甜橙6.5-7.5重量份、桑椹4.5-7.0重量份、杏鲍菇4.0-5.0重量份、广枣6.0-8.0重量份、芒果5.0-6.0重量份、毛冬瓜6.0-8.0重量份、越橘7.0-8.0重量份、银耳5.0-6.0重量份、龙眼6.0-8.0重量份。
在本发明的一个实施例中,所述中药组合物由以下原料制成:桃仁6.5重量份、红天葵5.0重量份、葡萄柚5.0重量份、甜橙5.5重量份、桑椹3.5重量份、杏鲍菇3.5重量份、广枣5.0重量份、芒果4.0重量份、毛冬瓜5.0重量份、越橘6.0重量份、银耳5.0重量份、龙眼5.5重量份。
在本发明的一个实施例中,所述中药组合物由以下原料制成:桃仁8.0重量份、红天葵8.5重量份、葡萄柚10.0重量份、甜橙8.5重量份、桑椹8.0重量份、杏鲍菇5.0重量份、广枣10.0重量份、芒果6.0重量份、毛冬瓜8.0重量份、越橘8.0重量份、银耳6.5重量份、龙眼8.5重量份。
本发明还提供所述中药组合物的制备方法,包括以下步骤:
粉碎所有组分,按比例加水20.0-50.0重量份,热回流提取,减压浓缩成稠膏,真空干燥,粉碎成细粉备用。
作为优选,所述热回流提取时间为3.5小时。
更优选的,所述减压浓缩及真空干燥温度为65℃;所述粉碎为过100~200目筛。
本发明还提供所述中药组合物为活性成分制备的中药制剂,作为优选,其为口服液、片剂、丸剂、颗粒剂、胶囊剂或凝胶剂。
本发明的另一个目的是提供所述中药组合物在制备治疗乳腺癌、卵巢癌、子宫内膜癌或子***的药物中的应用。
本发明所述中药组合物可用作外用药直接作用于肿瘤局部,使肿瘤凝固、坏死、溶解、脱落,还可以缓解宫颈水肿,减少或控制出血,抑制局部感染,促进肿瘤溃烂而愈合。应用本发明所述中药组合物保守治疗,也可作为***的术前准备用药,以改善手术条件。
放射治疗是治疗***主要治疗手段之一,放疗在杀死癌细胞的同时,对人体的正气损害严重,常引起便血、呕吐、腹泻、脱肛、放射性炎症、骨髓抑制等毒副反应。放疗时应用本发明所述中药配合治疗,可以减轻毒副反应,提高治愈率和生命生存概率。
***早期手术可提高生存率,中晚期患者和复发癌的手术效果较差,而运用该中药制剂治疗***手术患者,内服与外治相结合,可缓解临床症状,延长患者生命率。
体外实验MYr法和集落形成法结果显示本发明所述中药组合物对4类肿瘤细胞株T47D人乳腺癌细胞(ATCC)、Ho-8910人卵巢癌细胞株、HEC-1-A人子宫内膜癌细胞株和Hela人子***细胞株及集落形成生长有显著的抑制作用,其抑制率随着药物浓度增加而相应增高,提示本发明所述中药组合物及中药制剂在体外对肿瘤细胞生长具有抑制作用,具有广泛的临床应用前景。
附图说明
图l(a)为金丝桃苷对照品、(b)为本发明中药组合物中药制剂的HPLC谱图;*为金丝桃苷。
具体实施方式
本发明公开了一种抑制肿瘤细胞增殖的中药组合物、制备方法与用途,本领域技术人员可以借鉴本文内容,适当改进工艺参数实现。特别需要指出的是,所有类似的替换和改动对本领域技术人员来说是显而易见的,它们都被视为包括在本发明。本发明的产品、方法及应用已经通过较佳实施例进行了描述,相关人员明显能在不脱离本发明内容、精神和范围内对本文所述的方法和应用进行改动或适当变更与组合,来实现和应用本发明技术。
为了使本领域的技术人员更好地理解本发明的技术方案,下面结合具体实施例对本发明作进一步的详细说明。
实施例1:制备本发明所述中药组合物
称取桃仁6.5g、红天葵5.0g、葡萄柚5.0g、甜橙5.5g、桑椹3.5g、杏鲍菇3.5g、广枣5.0g、芒果4.0g、毛冬瓜5.0g、越橘6.0g、银耳5.0g、龙眼5.5g。
粉碎所有组分,按比例加水20.0-50.0g,热回流提取3.5小时,减压浓缩成稠膏,65℃真空干燥,过100~200目筛粉碎成细粉备用。
实施例2:制备本发明所述中药组合物
称取桃仁8.0g、红天葵8.5g、葡萄柚10.0g、甜橙8.5g、桑椹8.0g、杏鲍菇5.0g、广枣10.0g、芒果6.0g、毛冬瓜8.0g、越橘8.0g、银耳6.5g、龙眼8.5g。
粉碎所有组分,按比例加水20.0g,热回流提取3.5小时,减压浓缩成稠膏,65℃真空干燥,过100~200目筛粉碎成细粉备用。
实施例3:制备本发明所述中药制剂
桃仁7g、红天葵8.0g、葡萄柚6.0g、甜橙7.5g、桑椹4.5g、杏鲍菇5.0g、广枣6.0g、芒果6.0g、毛冬瓜8.0g、越橘7.0g、银耳6.5g、龙眼8.0g。
粉碎所有组分,加水50.0g,热回流提取3.5小时,减压浓缩成稠膏,65℃真空干燥,过100~200目筛粉碎成细粉,将细粉与等量去离子水混合得口服液。
实施例4:本发明所述中药组合物的体外临床实验
本实验将一种实施例1-3制备的中药组合物或中药制剂,在体外进行了抗癌活性研究,以证实所述中药组合物或中药制剂的疗效。
1
材料与仪器
1.1
实施例1或2或3制备的抑制肿瘤细胞增殖及胶原合的中药组合物或中药制剂。(以下简称中药组合物或中药制剂,代表含义相同)
1.2
肿瘤细胞株:T47D人乳腺癌细胞(ATCC)、Ho-8910人卵巢癌细胞株、购自上海雅吉细胞生物科技有限公司库;HEC-1-A人子宫内膜癌细胞株和Hela人子***细胞株、由中国医学科学院基础医学研究所细胞中心惠赠。
1.3
试剂MTT(四甲基噻唑蓝)为德国Sigm a公司产品;FBS(胎牛血清)由长春西诺生物科技有限公司提供;RPMI1640培养基为美国GIBCO公司产品;Tryp—isn(胰蛋白酶)由美国Gibco公司提供:DMSO(二甲基亚砜)由北京化学试剂公司提供;W right,s stain(瑞氏染色素)购自上海三爱思试剂有限公司;Giemsa,s stain(吉氏染色素)购自上海试剂三厂;卡那霉素,德国Sigma公司分装;L一谷氨酰胺,A m resco分装。
1.4
仪器CO2培养箱(Therm o Form a),美国产,型号:381;尼康倒置显微镜,日本产,型号:TE2000;酶标仪,美国宝特产,型号:Bio-Tek ELX800;
96孔板,丹麦产,型号:3072;低速台式离心机TD-5,上海赵迪生物科技有限公司,型号:TD6M;层析柱:各种不同规格口径的普通玻璃柱。
2
方法
2.1
RPM1640完全培养液的配置RPM I1640完全培养液含3%谷氨酰胺、卡那霉素750ug/ml、10%或15%FBS。
2.2
M T Y法测定在96孔培养板中每孔加入200ulxl(含有5000个/ml肿瘤细胞)10%FBS的RPM I1640培养液,置37℃,10%CO2培养箱中培养24h后(H22、S180离心处理),弃去旧培养液。实验组分别加入新的培养液190ul/孔,然后加入不同浓度本发明所述中药制剂10ul/孔,使终浓度分别为1.25,2.5,5,10,20,40,80ug/ml,对照孔则加入200ul/孔新的培养液。每组4平行孔,置37%,10%CO2培养液培养4d后,弃去上清液,加入200ul/孔新鲜配置的含0.2mg/ml M T Y的无血清培养液,37%继续培养4h。4h后弃上清液,加入200ul/孔D M SO,振荡混匀后,用酶标仪(波长为570nm,参比波长为450nm)测定OD值,按下式计算药物对肿瘤细胞生长的抑制率:肿瘤细胞生长抑制率(%)=(1一实验组平均OD值/对照组平均OD值)x100%。
2.3
集落形成法取对数生长期的T47D人乳腺癌细胞(ATCC)株和Ho-8910人卵巢癌细胞株,用胰蛋白酶消化成分散细胞悬液,用10%FBSRPMI1640培养液配成含500个/ml细胞悬液,取35mm培养皿,4个为一组,阴性对照组每皿加2ml细胞悬液。实验组加入一种抑制肿瘤纤维细胞增殖及胶原合成的中药制剂100ul,加入稀释后的细胞悬液2ml,使本发明所述中药制剂终浓度为20ug/ml,摇匀后置37℃10%CO2培养箱培养7d,弃去培养液,先用瑞氏染液染色5min,然后用Giemsa s溶液与Sorensen磷酸缓冲液以1:9配成洗液,染色10min。流水冲洗、晾干,在20x的显微镜下计数含50个细胞以上的集落,重复4次。其中HEC-1-A人子宫内膜癌细胞株和Hela人子***细胞株、用半固体软琼脂集落培养法,取对数生长期的HEC-1-A和Hela肿瘤细胞株,用15%FBSR PMI1640培养液配成含1000个/ml细胞悬液,置37℃预温。取35mm培养皿,4个为一组,每个实验组加入终浓度为20ug/ml的一种抑制肿瘤纤维细胞增殖及胶原合成的中药制剂100ul,对照组加入等体积的培养液,取在沸水中融化的5%琼脂液1份,加入到9份37℃含15%FBSRP-M I1640培养液中,摇匀后迅速加入到培养皿中,每个皿1ml,混匀后,置室温使琼脂凝固。取预温的细胞悬液按每9.4ml加5%的
琼脂液0.6ml的比例混匀,加到已铺底层琼脂的培养皿中,每皿lml,置室温使琼脂凝固。盖上培养皿盖,置37℃10%CO2培养箱培养7d,在16×的显微镜下计数直径大于75um(50个细胞以上)的集落。按下式计算集落抑制率:集落抑制率(%)=(1一克隆数/对照组克隆数)×100%。
2.4
统计学处理以SPSS10.0统计软件分析,两组问的均数比较采用t检验。
3
结果
3.1
MTr法测定本发明所述中药制剂对4种肿瘤细胞株生长的抑制作用,结果见表1~4。
表1本发明所述中药制剂对T47D人乳腺癌肿瘤细胞(ATCC)的抑制作用(ⅹ±s)
与对照组比较,P﹤0.01;n﹦4
表2本发明所述中药制剂对Ho-8910人卵巢癌肿瘤细胞的抑制作用(ⅹ±s)
与对照组比较,P﹤0.01;n﹦4
表3本发明所述中药制剂对HEC-1-A人子宫内膜癌肿瘤细胞的抑制作用(ⅹ±s)
与对照组比较,P﹤0.01;n﹦4
表4本发明所述中药组合物对Hela人子***肿瘤细胞的抑制作用(ⅹ±s)
与对照组比较,P﹤0.01;n﹦4
结果显示,本发明所述中药组合物对T47D人乳腺癌细胞(ATCC)、Ho-8910人卵巢癌细胞株、HEC-1-A人子宫内膜癌细胞株和Hela人子***细胞株有显著的抑制作用,并与浓度不同,呈正相关作用。
3.2
集落形成法观察本发明所述中药制剂对4种肿瘤细胞株抑制作用,结果见表5~8。
表5本发明所述中药组合物在浓度为20um/ml对T47D人乳腺癌肿瘤细胞集落形成的影响(ⅹ±s)%
与对照组比较,P﹤0.01;n﹦4
表6本发明所述中药组合物在浓度为20um/ml对Ho-8910人卵巢癌肿瘤细胞集落形成的影响(ⅹ±s)%
与对照组比较,P﹤0.01;n﹦4
表7本发明所述中药组合物在浓度为20um/ml对HEC-1-A人子宫内膜癌细胞集落形成的影响(ⅹ±s)%
与对照组比较,P﹤0.01;n﹦4
表8本发明所述中药制剂在浓度为20um/ml对Hela人子***细胞集落形成的影响(ⅹ±s)%
与对照组比较,P﹤0.01;n﹦4
结果显示集落形成法的结果显示,本发明所述中药制剂对T47D人乳腺癌细胞(ATCC)、Ho-8910人卵巢癌细胞株、HEC-1-A人子宫内膜癌细胞株和Hela人子***细胞株的集落形成有显著的抑制作用。
4
结论:本发明所述中药制剂实验通过采用两种不同的实验方法,研究其在体外抗肿瘤作用。MTr法、集落形成法是观察体外抗肿瘤活性的常用方法,尤其MTF法快速简便,常作为抗肿瘤药的体外初筛试验,本发明所述中药制剂研究采用两种实验方法的联合应用增加了实验结果的可靠性。MYr法和集落形成法的结果相吻合,显示本发明所述中药制剂对4类肿瘤细胞株生长有显著的抑制作用,其抑制率随着药物浓度增加而相应增高,提示本发明所述中药组合物或中药制剂在体外对肿瘤细胞生长具有抑制作用。
实施例5:本发明所述抑制肿瘤细胞增殖的中药组合物有效成分植物总多酚含量及检测方法
1仪器与试药
1.1仪器
752型紫外分光光度计(上海精密科学仪器有限公司);760CRT双光束紫外一可见分光光度计(北京普析通用仪器有限公司);BP一121S电子天平(天津仪器厂)。
1.2试药
一种抑制肿瘤细胞增殖的中药组合物供试品(实施例1-3);没食子酸对照品(中国药品生物制品检定所);乙醇、甲醇、醋酸钠、醋酸、碳酸钠、钨酸钠、磷酸等试剂均为分析纯。
2方法与结果
2.1溶液的制备
Folin试液的配制:称取10g钨酸钠置于圆底烧瓶中,用75mL的蒸馏水溶解,加人85%磷酸8mL,回流3h,冷却移人100mL量瓶中用蒸馏水定容。对照品溶液的制备:精密称取没食子酸对照品10.8mg,置于100mL棕色量瓶中,加入30%甲醇稀释至刻度,摇匀,即得每mL含没食子酸108ug的对照品溶液。供试品溶液制备:精密称取一种抑制肿瘤细胞增殖的中药组合物供试品0.1g,精密称定,置25mL量瓶中,加50%乙醇适量,超声30min,放冷用50%乙醇适量稀释至刻度,摇匀,即得。
2.2测定波长的选择
精密量取没食子酸对照品溶液、供试品溶液适量,分别置于10mL量瓶中,用0.1mol/L醋酸钠一醋酸缓冲液定容,摇匀,分别取1mL于10mL量瓶中,加Folin试液0.5mL,用2%碳酸钠溶液定容,放置30min显色。按照紫外分光光度法在400am一900nm波长范闹内扫描,结果显示,显色后没食子酸对照品溶液、一种抑制肿瘤细胞增殖的中药组合物供试品溶液在
730nln均有最大吸收峰,故选择730nm为测定波长。
2.3线性关系考察
分别吸取对照品溶液1.0mL,2.0mL,3.0mL,4.0mL,5.0mL,6.0mL,置于10mL量瓶中,用0.1mol/I。醋酸钠一醋酸缓冲液定容,摇匀,分别取1mL于10mL量瓶中,按2.2方法显色后放置30min,避光保存,在730nm处测定吸光度,以吸收度(A)为纵坐标,没食子酸浓度(C)为横坐标,绘制标准曲线,得到同归方程:A=0.1503C+0.0111(R=0.9999),结果表明,没食子酸在1.08ug/mL~6.48ug/mL范围内线性关系良好。
2.4精密度考察
精密量取对照品溶液3mL,置于10mL量瓶中,按2.2方法显色后避光放置30min,重复测定吸光度6次,RSD=0.5%,结果表明精密度良好。
2.5显色稳定性考察
精密量取供试品溶液1mL,置于10mL量瓶中,按2.2方法显色后避光保存,每隔10min测定吸光度,RSD=0.5%,结果表明供试品在显色20min一70rain内稳定。
2.6重现性考察
取同一批一种抑制肿瘤细胞增殖的中药组合物制备供试品溶液6份,分别精密餐取1mL,置于10mL量瓶中,按2.2方法显色后避光放置30mln。测定吸光度,RSD=1.8%,结果表明本法重现性良好。
2.7回收率试验
采取加样回收率,取已知含量的一种抑制肿瘤细胞增殖的中药组合物制备供试品溶液,精密量取0.5mL,置于3个10mL量瓶中,分别加入1.2mL、1.5mL、1.8mL对照品溶液(108ug/mL),然后用O.1mol/L醋酸钠一醋酸缓冲液定容,摇匀,分别取1mL于10mL量瓶中,按2.2方法显色后避光放置30min,测定吸光度,计算回收率,结果见表l。
表1加样回收率实验结果
2.8样品测定
按样品配制及测定方法测定了三个不同批次的一种抑制肿瘤细胞增殖的中药组合物中总多酚含量,结果见表2。
表2一种抑制肿瘤细胞增殖的中药组合物总多酚含量(n=3)
结果:
平均加样回收率99.7%,RSD=1.2%,说明该方法准确度良好。
结论:
植物总多酚的测定是用于本发明抑制肿瘤细胞增殖的中药组合物提供质量稳定、可靠的分析评价手段,对该制剂中间体的质量评价具有实际意义。
实施例6:本发明所述抑制肿瘤细胞增殖的中药组合物有效成分金丝桃苷含量及检测方法
1、仪器与试药
高效液相色谱仪:美国戴安公司输液泵,10UV检测器;金丝桃苷对照品:中国药品生物制品检定所提供,实施例1-3任一制备的抑制肿瘤细胞增殖的中药组合物中药制剂为供试样;甲醇为色谱纯,水为超纯水,其他试剂均为分析纯。
2方法与结果
2.1色谱条件色谱柱Diamonsil CI8柱(150mm×4.6mm,5Ixm);流动相:甲醇一水.冰醋酸(48:52:1);检测波长:340nm;体积流量:1ml/min;柱温:室温;进样量:10l;理论塔板数按金丝桃苷峰计算应不低于3000。在上述色谱条件下,金丝桃苷峰保留时间约为9min,见图1。
2.2对照品溶液的制备精密称取干燥至恒重的金丝桃苷对照品6.59mg。置50ml量瓶中,加50%乙醇溶解并稀释至刻度。混匀,即得(每1ml含金丝桃苷131.8Ixg)。
2.3供试品溶液的制备精密称取一种抑制肿瘤细胞增殖的中药组合物中药制剂供试样约0.2g,置50rnl量瓶中,加50%乙醇40ml,超声处理30rain,放冷,用50%乙醇稀释至刻度,摇匀,用微孔滤膜(0.45Ixm)滤过,取续滤液,即得。
2.4线性关系考察精密吸取金丝桃苷对照品溶液(131.8g/ml)1、2...345、6ml,置10ml量瓶中,加50%乙醇至刻度,混匀,微孔滤膜滤过。依次进样10l,按上述色谱条件操作。以峰面积为纵坐标,质量浓度为横坐标,进行线性回归,得回归方程Y=129003.7X十1026o8.0,r=0.9998。结果表明,金丝桃苷在l3.18—79.08-g/ml范围内与峰面积线性关系良好。
2.5方法学考察
2.5.1精密度实验精密吸取金丝桃苷对照品溶液(52.72g/ml)10l,重复进样6次,结果金丝桃苷峰面积的RSD为1.42%。
2.5.2稳定性实验取同一份一种抑制肿瘤细胞增殖的中药组合物中药制剂供试品溶液,分别在0,1,2,4,8,12,24h分别进样测定,结果金丝桃苷峰面积的RSD为1.58%,表明供试品溶液在24h内基本稳定。
2.5.3重现性实验精密称取同一批一种抑制肿瘤细胞增殖的中药组合物中药制剂供试品,平行取样5份制备供试品溶液,测定,结果金丝桃苷质量分数为12.0mg/g,RSD为2.73%。
2.5.4回收率实验采取加样回收法。精密称取已知含量的一种抑制肿瘤细胞增殖的中药组合物中药制剂供试品(含金丝桃苷12.0mg/g)5份,加入金丝桃苷对照品适量,按供试品溶液的制备方法操作,测定。结果见表3。
表3加样回收率考察结果
2.6样品测定将3个不同批次的供试品一种抑制肿瘤细胞增殖的中药组合物中药制剂制成供试品溶液,进样,测定峰面积,采用外标法计算金丝桃苷的质量分数。结果见表4。
表4金丝桃苷含量
结果:平均加样回收率为97.43%,RSD为1.26%(rt=5)
结论:该实验方法简便,快速、准确、可有效控制一种抑制肿瘤细胞增殖的中药组合物中药制剂质量稳定及有效成分的确立.
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.一种抑制肿瘤细胞增殖的中药组合物,由以下原料制成:桃仁6.5-8.0重量份、红天葵5.0-8.5重量份、葡萄柚5.0-10.0重量份、甜橙5.5-8.5重量份、桑葚3.5-8.0重量份、杏鲍菇3.5-5.0重量份、广枣5.0-10.0重量份、芒果4.0-6.0重量份、毛冬瓜5.0-8.0重量份、越橘6.0-8.0重量份、银耳5.0-6.5重量份、龙眼5.5-8.5重量份。
2.根据权利要求1所述的中药组合物,其特征在于,由以下原料制成:桃仁7-8.0重量份、红天葵6.0-8.0重量份、葡萄柚6.0-9.0重量份、甜橙6.5-7.5重量份、桑葚4.5-7.0重量份、杏鲍菇4.0-5.0重量份、广枣6.0-8.0重量份、芒果5.0-6.0重量份、毛冬瓜6.0-8.0重量份、越橘7.0-8.0重量份、银耳5.0-6.0重量份、龙眼6.0-8.0重量份。
3.根据权利要求1所述的中药组合物,其特征在于,由以下原料制成:桃仁6.5重量份、红天葵5.0重量份、葡萄柚5.0重量份、甜橙5.5重量份、桑葚3.5重量份、杏鲍菇3.5重量份、广枣5.0重量份、芒果4.0重量份、毛冬瓜5.0重量份、越橘6.0重量份、银耳5.0重量份、龙眼5.5重量份。
4.根据权利要求1所述的中药组合物,其特征在于,由以下原料制成:桃仁8.0重量份、红天葵8.5重量份、葡萄柚10.0重量份、甜橙8.5重量份、桑葚8.0重量份、杏鲍菇5.0重量份、广枣10.0重量份、芒果6.0重量份、毛冬瓜8.0重量份、越橘8.0重量份、银耳6.5重量份、龙眼8.5重量份。
5.根据权利要求1-4任一项所述中药组合物的制备方法,包括以下步骤:
粉碎所有组分,按比例加水20.0-50.0重量份,热回流提取,减压浓缩成稠膏,真空干燥,过100~200目筛粉碎成细粉备用。
6.根据权利要求5所述的制备方法,其特征在于,所述热回流提取时间为3.5小时。
7.根据权利要求5所述的制备方法,所述减压浓缩及真空干燥温度为65℃。
8.中药制剂,以权利要求1-4任一项所述中药组合物为活性成分。
9.根据权利要求8所述的中药制剂,其特征在于,其为口服液、片剂、丸剂、颗粒剂、胶囊剂或凝胶剂。
10.权利要求1-4任一项所述中药组合物在制备治疗乳腺癌、卵巢癌、子宫内膜癌或***的药物中的应用。
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CN1223886A (zh) * | 1998-12-03 | 1999-07-28 | 孙景华 | 一种具有祛邪扶正双向治疗作用的抗癌新药 |
CN103301201A (zh) * | 2013-06-28 | 2013-09-18 | 苏州菩芸生物科技有限公司 | 一种提高免疫力辅助抗肿瘤的中草药复方 |
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CN1223886A (zh) * | 1998-12-03 | 1999-07-28 | 孙景华 | 一种具有祛邪扶正双向治疗作用的抗癌新药 |
CN103301201A (zh) * | 2013-06-28 | 2013-09-18 | 苏州菩芸生物科技有限公司 | 一种提高免疫力辅助抗肿瘤的中草药复方 |
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