CN114886908A - 松果菊苷的医药用途 - Google Patents
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Abstract
本发明涉及药学领域,特别是涉及一种松果菊苷的制药用途。所述松果菊苷可用于制备防治结直肠癌肝转移的药物。
Description
技术领域
本发明属于医药领域,具体涉及松果菊苷的新应用。
背景技术
结直肠癌(Colorectal cancer,CRC)肝转移是结直肠癌治疗的重点和难点之一。中国临床肿瘤学会(CSCO)指南推荐化疗联合靶向治疗是转移性结肠癌的一线治疗方案,但化疗的毒副反应以及患者的耐药性,大大限制了治疗效果。因此,如何进一步延长转移性结直肠癌患者的生存时间,减少不良反应,提高生活质量,是亟待解决的问题。
松果菊苷(echinacoside,ECH)是从肉苁蓉中提取的一种天然苯乙醇苷类化合物,性状为白色结晶粉末。已有研究表明,松果菊苷具有广泛的药理作用,如神经保护作用、肝脏的保护作用、抗凋亡、抗衰老、免疫调节和促进生殖的作用,同时还具有降糖、降脂、促进骨形成以及抗肺动脉高压和预防动脉粥样硬化的作用。
发明内容
本发明旨在提供一种松果菊苷的新用途。
具体来说,本发明提供了一种松果菊苷在制备防治结直肠癌肝转移的药物中的应用。
在一优选例中,所述松果菊苷是作为唯一的活性成分用于制备防治结直肠癌肝转移的药物。
本发明各个方面的细节将在随后的章节中详尽描述。通过下文以及权利要求的描述,本发明的特点、目的和优势将更为明显。
附图说明
图1松果菊苷有效抑制C57BL6/J小鼠结直肠癌肝转移(n=6只/每组)
上图为各组小鼠肝脏肿瘤灶的数量及形态;下图为各组小鼠肝脏肿瘤灶病理学变化。
Model:模型组;ECH-L:松果菊苷低剂量组(20mg/kg/d);ECH-M:松果菊苷中剂量组(40mg/kg/d);ECH-H:松果菊苷高剂量组(80mg/kg/d);5-FU:阳性对照药氟尿嘧啶组。
具体实施方式
本发明的松果菊苷(echinacoside,ECH),别名:松果菊甙、海胆苷,分子式:C35H46O20,相对分子量786.72,其结构式如下:
本发明的松果菊苷可通过商业途径购买获得。其纯度均符合药用标准。松果菊苷的纯度以>98%最佳。
以将本发明的松果菊苷制成药物为例。本发明的松果菊苷可以单独使用或以药物组合物的形式使用。药物组合物包括作为主要活性成分的本发明的松果菊苷及可药用载体。通常,本发明的药物组合物应当含有0.1~99.9%重量百分比的本发明的活性天然成分松果菊苷。“可药用载体”不会破坏本发明的松果菊苷的药学活性;同时,其有效用量,即能发挥药物载体作用时的用量对人体无毒害作用。
所述可药用载体包括但不限于:软磷脂、硬脂酸铝、氧化铝、离子交换材料、自乳化药物传递系统、吐温或其他表面活化剂、血清蛋白、缓冲物质如磷酸盐、氨基乙酸、山梨酸、水、盐、电解质如硫酸盐精蛋白、磷酸氢二钠、磷酸氢钾、氯化钠、锌盐、硅酸镁、饱和脂肪酸部分甘油酯混合物等。
其他常用的药物辅料如粘合剂(如微晶纤维素)、填充剂(如淀粉、葡萄糖、无水乳糖和乳糖珠粒)、崩解剂(如交联PVP、交联羧甲基淀粉钠、交联羧甲基纤维素钠、低取代羟丙基纤维素)以及吸收促进剂、吸附载体、香味剂、甜味剂、赋形剂、稀释剂、润湿剂等。
本发明的松果菊苷以及其药物组合物可按本领域常规方法制备并通过胃肠道途径给药。口服制剂包括胶囊剂、片剂、口服液、颗粒剂、丸剂等。因此,本发明的松果菊苷以及其药物组合物的给药途径应选择口服递药途径。
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法,通常按照常规条件或按照制造厂商所建议的条件。除非另外说明,否则所有的百分数、比率、比例、或份数按重量计。
除非另行定义,文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。此外,任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。文中所述的较佳实施方法与材料仅作示范之用。
本发明提到的上述特征,或实施例提到的特征可以任意组合。本专利说明书所揭示的所有特征可与任何组合物形式并用,说明书中所揭示的各个特征,可以任何可提供相同、均等或相似目的的替代性特征取代。因此除有特别说明,所揭示的特征仅为均等或相似特征的一般性例子。
实施例一 松果菊苷抑制小鼠结直肠癌肝转移
1.实验材料
1.1实验用药物及试剂
松果菊苷(HPLC≥95%),成都瑞芬思生物科技有限公司;5-FU(氟尿嘧啶注射液),天津金耀药业有限公司。
1.2实验动物及饲养
C57BL/6J小鼠,6-7周龄,雄性。SPF级饲养于上海中医药大学动物实验中心,并取得动物伦理委员会批准。饲养条件:室温20±2℃,湿度55至65%,明暗交替,光照适度,通风洁净良好。
2.实验方法
2.1构建结直肠癌肝转移模型
小鼠适应实验室环境1周后,随机分为6组。小鼠术前备皮,常规消毒,腹腔注射1%戊巴比妥钠(50mg/kg)麻醉小鼠;右侧卧位固定小鼠,于左上腹横行切口约0.8-1.0厘米,以暴露脾脏;用胰岛素针于脾脏下极被膜下缓慢进针,将50μL(5*105个)处于生长对数期的MC38细胞悬液缓慢注入脾脏,可见小鼠脾脏被膜局部发白肿胀,酒精棉签压迫止血后把脾脏送回腹腔,缝合,关腹;按照分组计划进行给药,并饲养观察2周。所有小鼠于第21天实施安乐死,并收集样本进行后续实验。
2.2实验分组及给药
1)Model组:生理盐水(200μL,一日一次)灌胃2周后,行小鼠肠癌肝转移模型手术,术后第三天起继续灌胃2周;
2)ECH-L组:低剂量松果菊苷(20mg/kg/d,一日一次)灌胃两周后,行小鼠肠癌肝转移模型手术,术后第三天起继续灌胃2周;
3)ECH-M组:中剂量松果菊苷(40mg/kg/d,一日一次)灌胃两周后,行小鼠肠癌肝转移模型手术,术后第三天起继续灌胃2周;
4)ECH-H组:高剂量松果菊苷(80mg/kg/d,一日一次)灌胃两周后,行小鼠肠癌肝转移模型手术,术后第三天起继续灌胃2周;
5)5-FU组:行小鼠肠癌肝转移模型手术,术后第三天起氟尿嘧啶(15mg/kg,三日一次)腹腔注射2周。
2.3免疫组化染色
取小鼠肝脏组织切片脱蜡后,依次在无水乙醇、95%乙醇、85%乙醇和75%乙醇中再水合。用苏木精染色石蜡切片5-8min,然后在大量流水下冲洗返蓝。之后伊红染色1-3min后,超纯水清洗5s。脱水、封片与观察:将石蜡切片置于75%乙醇、85%乙醇、95%乙醇和无水乙醇中梯度脱水,再投入二甲苯I和II中5min,晾干、封片,染色组织在光学显微镜下观察分析。
2.4统计分析
数据分析使用GraphPad 8.0软件。P<0.05认为有统计学意义(图1、表1、表2)。
表1.松果菊苷显著减轻肝转移C57BL6/J小鼠的肝脏重量
组别 | 肝脏重量(g) | P值(与Model组相比) |
Model组 | 2.52±0.73 | — |
5-Fu组 | 1.75±0.3 | 0.0106* |
ECH-L组 | 1.86±0.19 | 0.0393* |
ECH-M组 | 1.65±0.27 | 0.0031** |
ECH-H组 | 1.32±0.13 | <0.0001*** |
注:Model:模型组;ECH-L:松果菊苷低剂量组(20mg/kg/d);ECH-M:松果菊苷中剂量组(40mg/kg/d);ECH-H:松果菊苷高剂量组(80mg/kg/d);5-FU:阳性对照药氟尿嘧啶组。统计学差异表示为*,p<0.05;**,p<0.01;***,p<0.001vs.Model组。
表2.松果菊苷有效减少肝转移C57BL6/J小鼠的肝转移灶数量
组别 | 肝转移灶数量 | P值(与Model组相比) |
Model组 | 10.14±2.48 | — |
5-Fu组 | 5.83±2.03 | 0.0228* |
ECH-L组 | 6±2.16 | 0.0305* |
ECH-M组 | 5.67±1.89 | 0.0170* |
ECH-H组 | 3.33±1.80 | 0.0002*** |
Model:模型组;ECH-L:松果菊苷低剂量组(20mg/kg/d);ECH-M:松果菊苷中剂量组(40mg/kg/d);ECH-H:松果菊苷高剂量组(80mg/kg/d);5-FU:阳性对照药氟尿嘧啶组。统计学差异表示为*,p<0.05;***,p<0.001vs.Model组。
实施例二 松果菊苷延长结直肠癌肝转移小鼠生存期
1.实验材料
1.1实验用药物及试剂
松果菊苷(HPLC≥95%),成都瑞芬思生物科技有限公司;5-FU(氟尿嘧啶注射液),天津金耀药业有限公司。
1.2实验动物及饲养
C57BL/6J小鼠,6-7周龄,雄性。SPF级饲养于上海中医药大学动物实验中心,并取得动物伦理委员会批准。饲养条件:室温20±2℃,湿度55至65%,明暗交替,光照适度,通风洁净良好。
2.实验方法
2.1构建结直肠癌肝转移模型
小鼠适应实验室环境1周后,随机分为6组。小鼠术前备皮,常规消毒,腹腔注射1%戊巴比妥钠(50mg/kg)麻醉小鼠;右侧卧位固定小鼠,于左上腹横行切口约0.8-1.0厘米,以暴露脾脏;用胰岛素针于脾脏下极被膜下缓慢进针,将50μL(5*105个)处于生长对数期的MC38细胞悬液缓慢注入脾脏,可见小鼠脾脏被膜局部发白肿胀,酒精棉签压迫止血后把脾脏送回腹腔,缝合,关腹;按照分组计划进行给药,观察并记录小鼠存活天数。
2.2实验分组及给药
1)Model组:生理盐水(200μL,一日一次)灌胃2周后,行小鼠肠癌肝转移模型手术,术后第三天起继续灌胃;
2)ECH组:高剂量松果菊苷(80mg/kg/d,一日一次)灌胃两周后,行小鼠肠癌肝转移模型手术,术后第三天起继续灌胃;
3)5-FU组:行小鼠肠癌肝转移模型手术,术后第三天起氟尿嘧啶(15mg/kg,三日一次)腹腔注射。
2.3统计分析
数据分析使用GraphPad 8.0软件。P<0.05认为有统计学意义(表3)。
表3.松果菊苷有效延长肝转移C57BL6/J小鼠的生存期
组别 | 中位生存期(d) | P值(与Model组相比) |
Model组 | 24.5 | — |
5-Fu组 | 30 | 0.0634 |
ECH组 | 37 | 0.0038** |
注:Model:模型组;ECH:松果菊苷高剂量组;5-FU:阳性对照药氟尿嘧啶组。统计学差异表示为**,p<0.01vs.模型组。
本发明所涉及的多个方面已做如上阐述。然而,应理解的是,在不偏离本发明精神之前提下,本领域专业人员可对其进行等同改变和修饰,所述改变和修饰同样落入本申请所附权利要求的覆盖范围。
Claims (2)
1.松果菊苷在制备防治结直肠癌肝转移的药物中的应用。
2.如权利要求1所述的应用,所述松果菊苷是作为唯一的活性成分用于制备防治结直肠癌肝转移的药物。
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Non-Patent Citations (2)
Title |
---|
韩一梅等: "松果菊苷对结肠癌SW480细胞体内外增殖、侵袭和转移的影响", 《广州中医药大学学报》, vol. 37, no. 8, pages 1542 - 1549 * |
马佶赟等: "血管内皮生长因子在结直肠癌肝转移中的研究进展", 《医学综述》, vol. 15, no. 4, pages 528 - 531 * |
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---|---|---|---|---|
CN115624627A (zh) * | 2022-09-01 | 2023-01-20 | 中国人民解放军空军军医大学 | 靶向cd226分子的抑制剂在抗肿瘤转移中的应用 |
WO2023179802A1 (zh) * | 2022-09-01 | 2023-09-28 | 中国人民解放军空军军医大学 | 靶向cd226分子的抑制剂在抗肿瘤转移中的应用 |
CN115624627B (zh) * | 2022-09-01 | 2024-04-12 | 中国人民解放军空军军医大学 | 靶向cd226分子的抑制剂在抗肿瘤转移中的应用 |
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