CN107106550A - 阿折地平在制备治疗癌症的医药组合物中的用途 - Google Patents
阿折地平在制备治疗癌症的医药组合物中的用途 Download PDFInfo
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- CN107106550A CN107106550A CN201580057616.5A CN201580057616A CN107106550A CN 107106550 A CN107106550 A CN 107106550A CN 201580057616 A CN201580057616 A CN 201580057616A CN 107106550 A CN107106550 A CN 107106550A
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- azelnidipine
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Abstract
本发明提供阿折地平在制备治疗癌症的医药组合物中的用途,所述癌症包括肺癌、膀胱癌、肾脏癌、子宫颈癌、前列腺癌、乳癌、卵巢癌、胃癌、肝癌、大肠癌、胰脏癌、舌癌等。
Description
本发明为阿折地平药物的新适应症的应用,尤其该阿折地平药物具有抑制多种癌症的用途。
阿折地平(Azelnidipine)是一种适用于治疗高血压的药物,可单独使用,也可与其他抗高血压药物合用。阿折地平是早已被FDA所认可的用药,具有大量药物机转及人体研究成果资料。
由于临床应用上的明显差异,因此从来没有人认为阿折地平具有抑制癌症细胞的可能性。
癌症长期高居全球死因之首,且罹患癌症人数更是逐年攀升,因此治疗癌症俨然成为重要的课题。一般来说,癌症药物治疗无论是化学治疗或标靶治疗,目的多是让癌细胞无法复制、分裂,来阻断肿瘤的蔓延扩张。根据统计,平均每一万个新药约只有五个能够进入第一期临床试验。进一步,许多癌细胞相继产生抗药性,使药物的使用成效大幅降低,最终导致癌症治疗失败。由此可见药物开发具有一定的困难程度。
因此,如何能让癌症药物的快速的可以被开发出来,并且尽可能的减少临床失败的机率,在癌症病学上是一个非常急迫又重要的课题。
发明内容
为解决上述的问题,本发明针对阿折地平药物进行新适应症的研发,而达到老药新用的目标。
经过实验设计结果显示阿折地平药物对正常细胞没有或仅有微小的毒性,但阿折地平在肿瘤细胞之间具有选择性的影响。
本发明提供一种阿折地平药物在用于制备治疗癌症的医药组合物中用途,其中所述医药组合物包含有效剂量的阿折地平及药学上可接受的盐类所组成。
本发明一实施例中,其中所述癌症是选自由胸腔相关癌症、腹腔
相关癌症、内分泌相关癌症、消化道相关癌症中的一种或多种。
本发明一实施例中,其中所述癌症是选自由骨肉瘤相关癌症、皮肤癌相关癌症中的一种或多种。
本发明一实施例中,其中所述胸腔相关癌症是指肺癌。
本发明一实施例中,其中所述腹腔相关癌症是选自由膀胱癌或/和子宫颈癌。
本发明一实施例中,其中所述内分泌相关癌症是选自由前列腺癌、乳癌、卵巢癌中的一种或多种。
本发明一实施例中,其中所述内分泌相关癌症是选自由胃癌、肝癌、大肠癌、胰脏癌及舌癌中的一种或多种。
本发明一实施例中,其中所述阿折地平药物的有效剂量浓度为20~500mg/kg/天。
图1显示本发明阿折地平用药应用于抑制癌细胞分析结果。
图2显示阿折地平用药可对肿瘤体积的效果
图3显示高剂量及低剂量阿折地平肿瘤生长的抑制效果
各种癌症细胞株建立
将不同癌症类型的细胞株进行继代培养,癌症细胞种类包含肺癌、胃癌、肝癌、直肠癌、皮肤癌、子宫颈癌、前列腺癌、膀胱癌、乳癌、血癌、胰腺癌、卵巢癌、舌癌、骨肉瘤、肾脏癌,并且对照组亦使用肾脏(HEK293(Kidney))、肺部上皮细胞BEAS-2B(Lung Epithelial)的正常细胞做测试。(表一)
先将各细胞于培养液培养后,由于各细胞的属性不同,因此针对不同种的细胞也要用相对应的培养液(表一),计算细胞数目,将2×106细胞数至入培养皿中,然后加入培养该细胞株的培养液补至体积为10ml,继续培养2-3天。之后将细胞计数,并分装至96孔盘,其中每孔的细胞数目固定为3000个细胞,且体积为100ul。
表一、癌症测试细胞株及其培养所用的培养液
细胞存活分析方法
将96孔盘中原有的培养液吸掉,每孔加入浓度10um、体积100ul的市售药物,放置72小时后,每孔再加入100ul已稀释的WST-1试剂,该稀释比例为培养液与WST-1原液的体积比为9:1,最后每个孔盘的总体积为200ul,然后将96孔盘放置于37℃,30~90分钟,利用elisa reader(酶联免疫检测仪)于OD450侦测吸光值,并计算各癌症细胞株的存活率。
阿折地平药对于各种癌细胞分析结果
阿折地平对胸腔相关癌症细胞抑制效果的测试
本分析阿折地平对胸腔相关癌症细胞抑制效果的测试,主要针对两种肺癌细胞进行测试,癌细胞株分别为A549和H1650两个细胞株,各做4次的癌细胞抑制实验结果,并且计算其平均值,结果表列如后。(表二)
表二、阿折地平对肺癌相关癌症细胞抑制测试
0524-10min | 0526-10min | 0529-10min | 0531-10min | 平均 | |
A549 | 81.4 | 118.6 | 69.7 | 80.2 | 87.5 |
1-10min | 2-20min | 3-20min | 4-20min | 平均 | |
H1650 | 28.8 | 26.5 | 40.5 | 62.7 | 39.7 |
阿折地平对腹腔相关癌症细胞抑制效果的测试
本分析阿折地平对腹腔相关癌症细胞抑制效果的测试,主要针对
两种腹腔相关癌症种类细胞进行测试,膀胱癌细胞株分别为TSGH和T24两个细胞株(表三),子宫颈癌细胞株分别为HeLa细胞株(表四),肾脏癌为786-O细胞株(表五),各做4次的癌细胞抑制实验结果,并且计算其平均值,结果表列如后。
表三、阿折地平对膀胱癌相关癌症细胞抑制测试
表四、阿折地平对子宫颈癌相关癌症细胞抑制测试
0524-10min | 0526-10min | 0529-10min | 0531-10min | 平均 | |
HeLa | 70.4 | 93.7 | 81.4 | 102.7 | 87.0 |
1 | 2 | 3 | 4 | 平均 | |
C-334 | 141.8 | 110.6 | 123.4 | 117.4 | 123.3 |
表五、阿折地平对肾脏癌相关癌症细胞抑制测试
1 | 2 | 3 | 4 | 平均 | |
786-O | 88.6 | 79.7 | 66.5 | 112.5 | 86.8 |
阿折地平对内分泌相关癌症细胞抑制效果的测试
本分析阿折地平对腹腔相关癌症细胞抑制效果的测试,主要针对三种内分泌相关癌症种类细胞进行测试,前列腺癌细胞株分别为PC-3和LNCap两个细胞株(表六),乳癌细胞株分别为MCF7和MDA-MB-231两个细胞株(表七),卵巢癌细胞株分别为NIH-OVCAR-3细胞株和TOV-21G(表八),各做4次的癌细胞抑制实验结果,并且计算其平均值,结果表列如后。
表六、阿折地平对前列腺癌相关癌症细胞抑制测试
表七、阿折地平对乳癌相关癌症细胞抑制测试
表八、阿折地平对卵巢癌相关癌症细胞抑制测试
阿折地平对消化道相关癌症细胞抑制效果的测试
分析阿折地平对消化道相关癌症细胞抑制效果的测试,主要针对五种消化道相关癌症种类细胞进行测试,胃癌细胞株分别为AGS和MKN-45两个细胞株(表九),肝癌细胞株分别为HepG2和Hep3B两个细胞株(表十),大肠癌细胞株分别为HCT116-wt和LoVo细胞株(表十一),胰脏癌细胞株分别为AsPC和BxPC细胞株(表十二),舌癌细胞株为SAS细胞株(表十三),各做4次的癌细胞抑制实验结果,并且计算其平均值,结果表列如后。
表九、阿折地平对胃癌相关癌症细胞抑制测试
表十、阿折地平对肝癌相关癌症细胞抑制测试
0524-20min | 0526-20min | 0529-20min | 0531-20min | 平均 | |
HepG2 | 110.3 | 87.2 | 112.1 | 93.7 | 100.8 |
0612-20min | 0614-20min | 0616-20min | 0619-20min | 平均 | |
Hep3B | 114.2 | 91.5 | 97.9 | 90.7 | 98.6 |
表十一、阿折地平对大肠癌相关癌症细胞抑制测试
0602-30min | 0605-10min | 0607-10min | 0609-10min | 平均 | |
HCT116-wt | 70.7 | 146.2 | 158.9 | 69.3 | 111.3 |
0616-10min | 0619-10min | 0621-10min | 0623-10min | 平均 | |
LoVo | 49.6 | 67.2 | 62.3 | 60.3 | 59.9 |
表十二、阿折地平对胰脏癌相关癌症细胞抑制测试
1-7-3-30min | 1-7-4-30min | 1-7-7-30min | 1-4-30min | 平均 | |
AsPC | 103.9 | 46.1 | 13.7 | 58.6 | 55.6 |
3-7-3-30min | 3-7-4-30min | 3-7-7-30min | 3-4-30min | 平均 | |
BxPC | 79.9 | 51.0 | 50.0 | 77.5 | 64.6 |
表十三、阿折地平对舌癌相关癌症细胞抑制测试
6-26-10min | 6-28-10min | 6-30-10min | 7-3-10min | 平均 |
SAS | 69.9 | 66.0 | 66.7 | 104.7 | 76.8 |
阿折地平对其他癌症细胞抑制效果的测试
分析阿折地平对其他类型癌正进行测试,骨肉癌细胞株为U2OS细胞株(表十四),皮肤癌细胞株分别为A375和BCC两个细胞株(表十五),各做3~4次的癌细胞抑制实验结果,并且计算其平均值,结果表列如后。
表十四、阿折地平对骨肉瘤相关癌症细胞抑制测试
6-26-10min | 6-28-10min | 6-30-10min | 7-3-10min | 平均 | |
U2OS | 53.3 | 78.3 | 84.8 | 61.2 | 69.4 |
表十五、阿折地平对皮肤癌相关癌症细胞抑制测试
0602-30min | 0605-10min | 0607-10min | 0609-10min | 平均 | |
A375 | 123.6 | 100.2 | 76.0 | 104.9 | 101.2 |
0602-30min | 0605-10min | 0607-10min | 0609-10min | 平均 | |
BCC | 77.7 | 127.2 | 95.7 | 100.2 |
对照组实验设计
阿折地平对正常细胞抑制效果的测试
分析阿折地平对多种正常细胞进行测试,正常肾脏细胞株为HEK293细胞株(表十六),正常肺部上皮细胞细胞株为BEAS-2B细胞株(表十七),各做4次的癌细胞抑制实验结果,并且计算其平均值,结果表列如后。
表十六、阿折地平对正常肾脏细胞抑制测试
平均 | |
HEK293 | 94.2 |
表十七、阿折地平对正常肺部上皮细胞抑制测试
0510-10min | 0512-10min | 0515-10min | 0517-10min | 平均 | |
BEAS-2B | 61.3 | 61.8 | 101.6 | 85.4 | 77.5 |
针对阿折地平对各种癌症细胞抑制效果汇整于表十八中,清楚看出阿折地平对于多项癌症有明显的抑制效果。经过发明人实验结果,阿折地平药物对于不同的癌症细胞有明显的抑制效果。(图一)
表十八、阿折地平对各种癌症细胞抑制效果的汇整
癌症细胞 | 抑制效果 |
肺癌 | 63.60 |
膀胱癌 | 97.30 |
子宫颈癌 | 87.00 |
肾脏癌 | 86.80 |
前列腺癌 | 60.45 |
乳癌 | 73.85 |
卵巢癌 | 64.80 |
胃癌 | 114.60 |
肝癌 | 99.70 |
大肠癌 | 85.60 |
胰脏癌 | 60.10 |
舌癌 | 76.80 |
骨肉癌 | 69.40 |
皮肤癌 | 100.70 |
正常细胞 | 抑制效果 |
肾脏 | 94.20 |
肺部上皮细胞 | 77.50 |
动物实验分析
本实验使用雌性BALB/cAnN.Cg-Foxn1nu/CrlNarl小鼠为样本(购自国家实验动物中心),体重为21±1g,皮下注射胃癌细胞(AGS)后随机分笼,测试药物分成三组:正常对照组、低剂量(100mg/kg/day)、高剂量(200mg/kg/day)。肿瘤形成超过100mm3后,每天采取腹腔注射方式给予药物;每周测量肿瘤大小两次,肿瘤体积测量公式如下:(L×W2);L代表肿瘤最长直径;W代表肿瘤最短直径。
依据第2图的结果,低剂量与高剂量的阿折地平均对肿瘤具有良好的抑制效果,且于实验过程中各组小鼠的重量均未出现明显降低的现象,因此表示阿折地平不论高低剂量在治疗过程均能使受测小鼠具有良好的健康状态而不死亡。
依据第3图的结果,高低剂量的阿折地平可有效减缓肿瘤体积增长,并可同时减少肿瘤体积,其中以高剂量的阿折地平具有较佳的效果。
上列详细说明是针对本发明之一可行实施例的具体说明,惟该实施例并非用以限制本发明的专利范围,凡未脱离本发明技艺精神所为的等效实施或变更,均应包含于本发明的专利范围中。
Claims (8)
- 一种阿折地平药物在用于制备治疗癌症的医药组合物中的用途,其特征是,所述医药组合物是选自由有效剂量的阿折地平(Azelnidipine)及药学上可接受的盐类所组成。
- 如权利要求1所述的用途,其特征是,所述癌症为胸腔相关癌症、腹腔相关癌症、内分泌相关癌症、消化道相关癌症中的一种或多种。
- 如权利要求1所述的用途,其特征是,所述癌症是选自骨肉瘤相关癌症、皮肤癌相关癌症中的一种或多种。
- 如权利要求2所述的用途,其特征是,所述胸腔相关癌症是指肺癌。
- 如权利要求2所述的用途,其特征是,所述腹腔相关癌症是选自膀胱癌、子宫颈癌、肾脏癌中的一种或多种。
- 如权利要求2所述的用途,其特征是,所述内分泌相关癌症系选自由前列腺癌、乳癌、卵巢癌中的一种或多种。
- 如权利要求2所述的用途,其特征是,所述消化道相关癌症系选自由胃癌、肝癌、大肠癌、胰脏癌、舌癌中的一种或多种。
- 如权利要求1所述的用途,其特征是,所述有效剂量浓度为每日20mg/kg~500mg/kg。
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Families Citing this family (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK3219705T3 (da) | 2005-12-28 | 2020-04-14 | Vertex Pharma | Farmaceutiske sammensætninger af den amorfe form af n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinolin-3-carboxamid |
WO2016062277A1 (zh) * | 2014-10-24 | 2016-04-28 | 朗齐生物医学股份有限公司 | 驱虫药用于制备抗癌医药组合物中的应用 |
EP3236967B1 (en) | 2014-12-22 | 2019-10-16 | SUDA Pharmaceuticals Ltd | Prevention and treatment of metastatic disease in thrombocytotic cancer patients |
WO2017116049A1 (ko) * | 2015-12-31 | 2017-07-06 | 경북대학교 산학협력단 | 설폰아마이드계 화합물을 유효성분으로 포함하는 암의 치료 및 전이 억제용 약학적 조성물 |
EP3241562A1 (en) * | 2016-05-02 | 2017-11-08 | Fundació Institut Mar d'Investigacio Medica | Zonisamide for use in the treatment of breast cancer |
CN106074474A (zh) * | 2016-06-15 | 2016-11-09 | 中南大学湘雅医院 | 羟苄丝肼及其在药学上可接受的盐在制备抗肿瘤药物方面的应用 |
WO2018072135A1 (zh) * | 2016-10-19 | 2018-04-26 | 微菌方舟生物科技股份有限公司 | 二氢吡啶类钙拮抗剂用于治疗癌症的用途 |
CN108066345A (zh) * | 2016-11-14 | 2018-05-25 | 武汉华杰世纪生物医药有限公司 | 一种具有抗肿瘤作用的化合物 |
KR102614709B1 (ko) | 2016-12-20 | 2023-12-18 | 에르테에스 로만 테라피-시스테메 아게 | 아세나핀 및 폴리실록산 또는 폴리이소부틸렌을 함유하는 경피흡수 치료 시스템 |
PL3338768T3 (pl) | 2016-12-20 | 2020-05-18 | Lts Lohmann Therapie-Systeme Ag | Transdermalny system terapeutyczny zawierający asenapinę |
US20200179404A1 (en) * | 2017-06-09 | 2020-06-11 | Regents Of The University Of Minnesota | Skin care formulations and skin cancer treatment |
EP3644973B1 (en) | 2017-06-26 | 2021-03-24 | LTS LOHMANN Therapie-Systeme AG | Transdermal therapeutic system containing asenapine and silicone acrylic hybrid polymer |
US20200129492A1 (en) * | 2017-07-03 | 2020-04-30 | Menri Group Ltd. | Treatment of cancer with dihydropyridines |
JP2019064976A (ja) * | 2017-10-03 | 2019-04-25 | 国立大学法人 熊本大学 | 抗がん剤 |
KR101933805B1 (ko) | 2017-10-17 | 2018-12-28 | 성균관대학교산학협력단 | 옥셀라딘시트레이트를 유효성분으로 포함하는 뇌암 예방 또는 치료용 약학적 조성물 |
CN108186652A (zh) * | 2017-12-28 | 2018-06-22 | 深圳大学 | 缝隙连接细胞间通迅抑制剂甘珀酸在制备预防和治疗肝细胞癌药物中的应用 |
CN111670050A (zh) | 2018-01-30 | 2020-09-15 | 爱普宁公司(特拉华) | 用于治疗睡眠呼吸暂停的方法和组合物 |
US11931366B2 (en) * | 2018-04-19 | 2024-03-19 | Washington University | Compositions and methods of use thereof for treatment of proteinopathies |
CA3101420A1 (en) | 2018-06-20 | 2019-12-26 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
FR3090084B1 (fr) | 2018-12-18 | 2023-10-13 | Securengy | Projectile pour armes à feu ou air comprimé pour emport liquide ou pulvérulent. |
WO2020132253A1 (en) * | 2018-12-19 | 2020-06-25 | University Of Vermont And State Agricultural College | Cancer therapeutic compositions and methods |
EP3949959A4 (en) * | 2019-04-04 | 2022-05-11 | Daegu-Gyeongbuk Medical Innovation Foundation | PHARMACEUTICAL COMPOSITION COMPRISING TRIMEBUTINE, OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, USED AS AN ACTIVE INGREDIENT FOR THE PREVENTION OR TREATMENT OF CANCER |
US20220202771A1 (en) * | 2019-04-05 | 2022-06-30 | University Of North Texas Health Science Center At Fort Worth | Antidepressants for the Treatment or Prevention of Memory Loss and/or Cognitive Decline or Dysfunction in Aging |
US20220146492A1 (en) * | 2019-04-11 | 2022-05-12 | Ian Basil Shine | Cell membrane permeability restoring therapy |
CN110179803A (zh) * | 2019-05-31 | 2019-08-30 | 天津科技大学 | 一种噻吨溴类化合物的应用 |
CN110742890A (zh) * | 2019-10-24 | 2020-02-04 | 暨南大学 | 洛美利嗪在制备抗结肠癌药物中的应用 |
CN110876800B (zh) * | 2019-11-18 | 2023-06-27 | 中南大学 | 米卡芬净在制备抗肿瘤药物中的应用及抗肿瘤药物 |
CN110840887A (zh) * | 2019-11-18 | 2020-02-28 | 杭州彗搏科技有限公司 | 三氯苯达唑在制备治疗乳腺癌的药物中的应用 |
CN111067899B (zh) * | 2020-01-08 | 2021-03-05 | 温州医科大学 | 一种抗疟药物磷酸伯氨喹在制备治疗白血病药物上的应用 |
US11304969B2 (en) * | 2020-01-24 | 2022-04-19 | The Florida International Univeristy Board Of Trustees | Treatments of prostate cancer |
CN111973593A (zh) * | 2020-05-09 | 2020-11-24 | 深圳市罗湖区人民医院 | 硝唑尼特及其药学上可接受的盐在制备治疗膀胱癌药物中的用途 |
CN111557941A (zh) * | 2020-06-15 | 2020-08-21 | 浙江大学 | Plod2的小分子抑制剂米诺地尔在肿瘤治疗中的应用 |
CN111848717A (zh) * | 2020-08-07 | 2020-10-30 | 四川大学 | 靶向调控线粒体能量代谢的化合物及其应用和药物 |
CN112274525B (zh) * | 2020-12-04 | 2022-04-08 | 遵义医科大学 | 一种化疗药物组合物及其应用 |
CN112336725A (zh) * | 2020-12-11 | 2021-02-09 | 吴照球 | 甲氧苄啶的医药新用途 |
CN112569342A (zh) * | 2020-12-21 | 2021-03-30 | 中南大学 | 卡泊芬净和/或其可药用盐在制备抗肿瘤药物中的应用及抗肿瘤药物 |
CN112569215A (zh) * | 2020-12-30 | 2021-03-30 | 东莞市人民医院 | 度米芬在制备防治结直肠癌的药物中的应用 |
EP4108244A1 (en) * | 2021-06-25 | 2022-12-28 | Universität Regensburg | Ss-lactam antibiotic with significant activity against cancer e.g. colon malignancies |
CN113663071B (zh) * | 2021-06-28 | 2022-12-30 | 四川大学 | Fbxl2激活剂在制备治疗egfr驱动的肺癌的药物中的用途 |
WO2023006954A1 (en) | 2021-07-30 | 2023-02-02 | Fundació Institut D'investigació Biomèdica De Bellvitge (Idibell) | Asenapine for use in cancer |
WO2023035200A1 (zh) * | 2021-09-09 | 2023-03-16 | 中国福利会国际和平妇幼保健院 | 五氟利多在制备治疗子宫内膜癌的药物中的应用 |
CN115887455B (zh) * | 2022-08-04 | 2024-04-05 | 北京大学人民医院 | 钙离子通道阻滞剂阿折地平在制备治疗子宫内膜癌的药物中的应用 |
CN115778957B (zh) * | 2022-11-04 | 2024-06-21 | 天津中医药大学 | 千金藤素及包含其的组合物用于预防或治疗酒精性肝病的应用 |
CN116570579A (zh) * | 2023-06-13 | 2023-08-11 | 深圳市泛谷药业股份有限公司 | 一种含有阿戈美拉汀和氟伏沙明的药物组合物及其应用 |
CN118059099B (zh) * | 2024-04-19 | 2024-06-14 | 四川大学华西医院 | 帕罗西汀联合asct2抑制剂用于制备治疗肝癌的药物中的应用及药物组合物 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014018563A2 (en) * | 2012-07-23 | 2014-01-30 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for the treatment of cancer |
CN103930132A (zh) * | 2011-09-27 | 2014-07-16 | 拜奥迈德瓦利探索有限公司 | 治疗胶质瘤的组合物和方法 |
Family Cites Families (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3844491B2 (ja) * | 1993-10-01 | 2006-11-15 | シンテックス(ユー・エス・エイ)インコーポレイテッド | ミコフェノール酸モフェチル高用量経口用懸濁剤 |
CA2207333C (en) * | 1994-12-28 | 2006-10-17 | Janssen Pharmaceutica, Naamloze Vennootschap | Use of nebivolol as an anti-atherogenic |
SI1113797T1 (sl) * | 1998-09-15 | 2010-02-26 | Lilly Co Eli | Uporaba duloksetina pri zdravljenju fibromialgije |
US6927223B1 (en) * | 2000-05-26 | 2005-08-09 | Washington State University Research Foundation | Use of serotonin agents for adjunct therapy in the treatment of cancer |
KR100699390B1 (ko) * | 2000-07-07 | 2007-03-28 | 트러스티즈 오브 터프츠 칼리지 | 9-치환된 미노사이클린 화합물 |
IL139975A0 (en) * | 2000-11-29 | 2002-02-10 | Univ Ramot | Anti proliferative drugs |
US20040072824A1 (en) * | 2001-06-01 | 2004-04-15 | Adam Telerman | Methods and compositions for the treatment of cancer |
GB0202337D0 (en) * | 2002-02-01 | 2002-03-20 | Univ Birmingham | Cancer treatment |
US7135575B2 (en) * | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
WO2005027842A2 (en) * | 2003-09-18 | 2005-03-31 | Combinatorx, Incorporated | Combinations of drugs for the treatment of neoplasms |
AU2004288714A1 (en) * | 2003-11-06 | 2005-05-26 | Celgene Corporation | Methods and compositions using thalidomide for the treatment and management of cancers and other diseases. |
KR100775549B1 (ko) * | 2004-05-12 | 2007-11-16 | 주식회사바이오러넥스 | 나이아신아마이드 또는 그의 유도체를 유효한 성분으로포함하는 암 예방 및 치료제 |
KR101171408B1 (ko) * | 2004-05-21 | 2012-08-08 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 테트라사이클린 및 이의 유사체의 합성 |
CN1279980C (zh) * | 2004-10-14 | 2006-10-18 | 孔庆忠 | 一种抗实体肿瘤药物组合物 |
JP2006298781A (ja) * | 2005-04-15 | 2006-11-02 | Geno Membrane:Kk | エストロン3硫酸トランスポーター活性阻害剤 |
TW200716141A (en) * | 2005-05-05 | 2007-05-01 | Combinatorx Inc | Compositions and methods for treatment for neoplasms |
CN101223149A (zh) * | 2005-07-05 | 2008-07-16 | 特瓦制药工业有限公司 | 制备缬沙坦的方法 |
EP1909778B1 (en) * | 2005-07-28 | 2017-12-13 | Academisch Ziekenhuis bij de Universiteit van Amsterdam | Monophenol, benzenediol, or sulfhydryl compounds for use in the treatment of melanomas |
US8148356B2 (en) * | 2005-08-24 | 2012-04-03 | Cumberland Pharmaceuticals, Inc. | Acetylcysteine composition and uses therefor |
CA2645494C (en) * | 2006-03-23 | 2016-01-12 | Amgen Inc. | Methods and compositions for making and using polymorphs of cinacalcet |
CN101099724A (zh) * | 2006-07-07 | 2008-01-09 | 上海复旦复华药业有限公司 | 一种微粉化来曲唑及其组合物 |
CN101103976A (zh) * | 2006-07-14 | 2008-01-16 | 海南盛科生命科学研究院 | 一种含阿那曲唑的口服药物组合物及其制备工艺 |
MX2009007247A (es) * | 2007-01-05 | 2009-09-18 | Cornerstone Therapeutics Inc | Metodo para el tratamiento de afecciones asociadas con actividad aumentada de 5-lipoxigenasa y/o leucotrienos. |
CN101730526A (zh) * | 2007-03-07 | 2010-06-09 | 阿布拉科斯生物科学有限公司 | 作为抗癌剂的包含雷帕霉素和白蛋白的纳米颗粒 |
AU2008269181B2 (en) * | 2007-06-21 | 2014-04-17 | Amgen Inc. | Methods of synthesizing cinacalcet and salts thereof |
WO2009025854A1 (en) * | 2007-08-22 | 2009-02-26 | Burnham Institute For Medical Research | Smips: small molecule inhibitors of p27 depletion in cancers and other proliferative diseases |
US20120082659A1 (en) * | 2007-10-02 | 2012-04-05 | Hartmut Land | Methods And Compositions Related To Synergistic Responses To Oncogenic Mutations |
CN100563645C (zh) * | 2007-12-06 | 2009-12-02 | 济南帅华医药科技有限公司 | 一种治疗实体肿瘤的蓓萨罗丁缓释植入剂 |
WO2009126274A2 (en) * | 2008-04-08 | 2009-10-15 | New York University School Of Medicine | Methods and compositions for the treatment of cancers, such as melanomas and gliomas |
CN101569624A (zh) * | 2008-04-29 | 2009-11-04 | 石药集团中奇制药技术(石家庄)有限公司 | 氨氯地平在制备治疗细胞增生性疾病药物中的用途 |
EP2123626A1 (en) * | 2008-05-21 | 2009-11-25 | Laboratorios del Dr. Esteve S.A. | Co-crystals of duloxetine and co-crystal formers for the treatment of pain |
WO2009147169A1 (en) * | 2008-06-03 | 2009-12-10 | Universite Paris Diderot-Paris 7 | Pharmaceuticl compositions useful for the treatment of cancers, in particular acute myeloid leukemia and acute promyelocytic leukemia |
CN101612400A (zh) * | 2009-07-22 | 2009-12-30 | 陈志龙 | 血管紧张素ⅱ的1型受体拮抗剂在抗肿瘤中的应用 |
CN101690816A (zh) * | 2009-08-16 | 2010-04-07 | 王丽燕 | 含钙拮抗剂、aⅱ受体拮抗剂和他汀类药的药物组合物 |
CN101991553B (zh) * | 2009-08-21 | 2015-02-25 | 北京以岭生物工程技术有限公司 | 一种依西美坦片及其制备方法 |
CN101863806B (zh) * | 2010-03-18 | 2013-02-13 | 湖北省医药工业研究院有限公司 | 抗前列腺癌药物(r)-比卡鲁胺的制备方法 |
US9012511B2 (en) * | 2010-05-19 | 2015-04-21 | Alkermes Pharma Ireland Limited | Nanoparticulate cinacalcet compositions |
US9018438B2 (en) * | 2010-07-29 | 2015-04-28 | Kyoto University | Screening method for anticancer drugs |
WO2012079232A1 (zh) * | 2010-12-15 | 2012-06-21 | Lai Hung-Cheng | 用于治疗癌症的化合物及其应用 |
CN102631354B (zh) * | 2011-02-11 | 2015-01-21 | 广东泰禾医药科技有限公司 | 含维生素d3和二甲双胍的药物组合物 |
CN102688493B (zh) * | 2011-03-25 | 2014-09-10 | 鼎泓国际投资(香港)有限公司 | 含有白藜芦醇及白藜芦醇类衍生物和Bc1-2抑制剂的药物组合物及其应用 |
CN102813643B (zh) * | 2011-06-10 | 2014-09-24 | 北京蛋白质组研究中心 | bumetanide在抑制肝癌细胞转移中的应用 |
AU2012335009B2 (en) * | 2011-11-10 | 2017-08-31 | Kai Pharmaceuticals, Inc. | Calcimimetics and methods for their use |
CN102600077B (zh) * | 2012-03-29 | 2013-06-05 | 江苏豪森药业股份有限公司 | 吉西他滨或其盐纳米乳剂注射液及其制备方法 |
ES2384069B1 (es) * | 2012-03-29 | 2013-07-04 | Hospital Sant Joan De Déu | Cinacalcet y tumores neuroblásticos |
CN103536607A (zh) * | 2012-07-10 | 2014-01-29 | 邵金辉 | 土霉素,普罗帕酮和安乃近的抗肿瘤作用 |
WO2014036654A1 (en) * | 2012-09-06 | 2014-03-13 | Mcmaster University | Compounds and methods for selectively targeting cancer stem cells |
BR112015006176B1 (pt) * | 2012-09-21 | 2023-04-18 | Intensity Therapeutics, Inc | Uso de um agente terapêutico e de um agente de intensificação de permeação intracelular |
EA037368B1 (ru) * | 2012-10-04 | 2021-03-19 | Аб Сьянс | Способ лечения рака поджелудочной железы у пациента, страдающего от связанной с болезнью интенсивной боли, и применение набора, содержащего маситиниб или его фармацевтически приемлемую соль и гемцитаниб, для лечения рака поджелудочной железы |
CN103356687B (zh) * | 2012-10-19 | 2016-06-01 | 厦门大学 | 一种伊维菌素及其衍生物的用途 |
WO2014108571A2 (en) * | 2013-01-14 | 2014-07-17 | Biocopea Limited | Cancer drug and uses |
CN103933569B (zh) * | 2013-01-22 | 2017-01-11 | 复旦大学 | 一种抗肺癌药物组合物及其应用、药盒和包装件 |
US9890127B2 (en) * | 2013-03-11 | 2018-02-13 | The Broad Institute, Inc. | Compounds and compositions for the treatment of cancer |
US20140271727A1 (en) * | 2013-03-18 | 2014-09-18 | National Yang-Ming University | Method of using an antidepressant for increasing immunity of a subject and treating cancer |
CN104161759B (zh) * | 2013-05-16 | 2019-10-08 | 中国科学院上海药物研究所 | 阿那格雷及其衍生物的抗肿瘤用途 |
CN103396419A (zh) * | 2013-08-13 | 2013-11-20 | 海宁市绿升医药科技有限公司 | 肿瘤光动力治疗药二氢卟吩e6-15-乙酯及其制备方法 |
CN103536925B (zh) * | 2013-10-28 | 2015-07-01 | 中国医学科学院基础医学研究所 | 强心苷化合物在非小细胞肺癌治疗中的应用 |
CN103622975B (zh) * | 2013-11-07 | 2016-06-15 | 广东药学院 | 格列吡嗪在制备治疗肿瘤药物中的应用 |
WO2015157471A1 (en) * | 2014-04-08 | 2015-10-15 | The Methodist Hospital | Inos-inhibitory compositions and their use as breast cancer therapeutics |
WO2016062277A1 (zh) * | 2014-10-24 | 2016-04-28 | 朗齐生物医学股份有限公司 | 驱虫药用于制备抗癌医药组合物中的应用 |
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