CN102939086A - 胃癌的治疗方法 - Google Patents
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Abstract
公开了治疗胃癌的方法和化合物。
Description
交叉引用美国相关专利申请
本申请案主张2010年4月19日提交的美国临时专利申请案第61/325,586号的权益。
技术领域
本发明总体上涉及用于治疗癌症的药物成分和方法,特别地涉及钌(Ⅲ)络合物,及其它的使用方法。
发明背景
胃癌是最致命的癌症类型之一。胃癌的治疗选择是有限的。外科手术和放射治疗可用于早期胃癌,但是对晚期或是复发性胃癌不是很有效。传统的化疗药物例如氟尿嘧啶和顺铂效果非常有限还常常导致严重的副作用。因此,存在对于治疗胃癌的新药剂和方法的重要的未满足的需求。
发明概述
本发明提供治疗胃癌的方法。一方面,本发明提供了一种对于胃癌的治疗、预防或延缓发病的方法,其中包括给胃癌患者摄入有效治疗或预防剂量的反式-[四氯双(1H-吲唑)钌(III)]在药学上可接受的盐(例如:反式-[四氯双(1H-吲唑)钌(III)]钠盐或反式-[四氯双(1H-吲唑)钌(III)]钾盐)。
另一方面,提供了一种对于抵抗性胃癌的治疗、预防或延缓发病的方法,包括给患者摄入有效治疗或预防剂量的反式-[四氯双(1H-吲唑)钌(III)]碱金属盐(例如:反式-[四氯双(1H-吲唑)钌(III)]钠盐或反式-[四氯双(1H-吲唑)钌(III)]钾盐)。
本发明还提供了反式-[四氯双(1H-吲唑)钌(III)]碱金属盐(例如:反式-[四氯双(1H-吲唑)钌(III)]钠盐或反式-[四氯双(1H-吲唑)钌(III)]钾盐)在制备用于本发明方法的药物中的应用。
本发明的以上所述及其它优点和特征以及实现这些特征和优势的方式,在考虑下面有关本发明的详细描述以及所附的表现优选范例性实施方案的例子之后将会更加明了。
附图概述
图1显示了用MTT法在胃癌细胞株NCI-N87中反式-[四氯双(1H-吲唑)钌(III)]钠盐能剂量依赖性地抑制生长。X轴是nM的药物浓度,Y轴是吸光度的对照百分比。
发明详述
本发明至少部分基于化合物反式-[四氯双(1H-吲唑)钌(III)]钠盐在治疗胃癌特别有效这一发现。因此,本发明的第一方面,提供治疗胃癌的方法。该方法包括用有效治疗剂量的反式-[四氯双(1H-吲唑)钌(III)]或其药学上可接受的盐对需要治疗的患者进行治疗。这样的盐包括反式-[四氯双(1H-吲唑)钌(III)]吲哚盐或碱金属盐(例如:反式-[四氯双(1H-吲唑)钌(III)]钠盐或反式-[四氯双(1H-吲唑)钌(III)]钾盐)。即,本发明是直接使用有效剂量的一种反式-[四氯双(1H-吲唑)钌(III)]或它的一种药学上可接受的盐来制备治疗胃癌的药物用于治疗被诊断为具有胃癌的患者。
本发明的方法可用于胃的各种恶性肿瘤,包括但不限于胃腺癌、MALT淋巴瘤(淋巴癌)、间质瘤和胃肠道间质瘤(GIST)。
本发明的这一方面的各种实施方案中,治疗方法还可选择包括一个诊断或鉴别患者是否患有胃肿瘤的步骤。然后对被诊断的患者施用本发明有效剂量的反式-[四氯双(1H-吲唑)钌(III)]或药学上可接受的盐,最好是一种碱金属盐,例如:反式-[四氯双(1H-吲唑)钌(III)]钠盐。各种胃癌可以用任何已知的传统方法诊断,这些方法包括CT扫描、内窥镜检查、钡X光相片、活组织检查等。
此外,在本发明的另一方面,提供了一种治疗抵抗性胃癌的方法,包括用有效治疗剂量的反式-[四氯双(1H-吲唑)钌(III)]或其药学上可接受的盐,最好是一种碱金属盐(例如:反式-[四氯双(1H-吲唑)钌(III)]钠盐或反式-[四氯双(1H-吲唑)钌(III)])钾盐来治疗诊断为具有抵抗性胃癌的患者。
此处使用的“抵抗性胃癌”这个术语,指的是对一种抗肿瘤治疗(不含反式-[四氯双(1H-吲唑)钌(III)]或药学上可接受的盐)没有有效反应,或对一种抗肿瘤治疗(不含反式-[四氯双(1H-吲唑)钌(III)]或药学上可接受的盐)有效反应后又发生复发、重返的胃癌。因此,此处使用的“对一种治疗方案有抵抗性的胃癌”,是指这种胃癌对这种治疗方案没有应答或有抗性,或者对这种治疗有应答之后又发生复发。
为了检测耐药性胃癌,可以通过仔细监控经历过初始治疗的患者的抗性、无应答性、或复发性的征兆。这可以通过检测患者的恶性肿瘤对初始治疗的反应。癌症对初始治疗的反应、无反应、或复发可以由任何合适的已普遍应用方法来检测确定。例如,可以通过评估肿瘤的大小和数目来确定,肿瘤大小或数目的增加表现肿瘤对化疗没有反应,或说明发生复发,做出确定的依据可以是Therasse et al,J.Natl.CancerInst.92:205-216(2000)的详细描述是实体瘤疗效评价标准(“RECIST”)。
依照本发明的另一方面,提供了一种预防或延迟胃癌发病,或预防或延迟胃癌复发的方法,包括给需要预防或延迟的患者摄入有效预防剂量的适合药用的反式-[四氯双(1H-吲唑)钌(III)]或者一种其药学上可接受的盐,最好是一种反式-[四氯双(1H-吲唑)钌(III)]碱金属盐(例如:反式-[四氯双(1H-吲唑)钌(III)]钠盐或反式-[四氯双(1H-吲唑)钌(III)])钾盐。
为了预防或延迟胃癌的复发,已经接受过治疗并且得到缓解、或病情稳定、或处于无进展状态的胃癌患者,可以用有效预防剂量的适合药用的反式-[四氯双(1H-吲唑)钌(III)]碱金属盐(例如:反式-[四氯双(1H-吲唑)钌(III)]钠盐或反式-[四氯双(1H-吲唑)钌(III)])钾盐进行治疗,能够有效预防或延迟胃癌的复发。
此处用到的短语“用……治疗……”或它的改述,意思是给患者摄入一种化合物或引起患者体内一种化合物的形成。
依照本发明提供的方法,胃癌可以用一种有效治疗剂量的适合药用的反式-[四氯双(1H-吲唑)钌(III)]或其药学上可接受的盐,最好是一种反式-[四氯双(1H-吲唑)钌(III)]碱金属盐来治疗,这类药物可以单独使用,也可以与一种或几种其它抗癌药物联合使用。
反式-[四氯双(1H-吲唑)钌(III)]碱金属盐可以用在本领域内任何已知的方法制备。例如,PCT公布号WO/2008/154553公开了一个高效的制作反式-[四氯双(1H-吲唑)钌(III)]钠盐的方法。
药物化合物例如反式-[四氯双(1H-吲唑)钌(III)]钠盐可以通过静脉注射或口服或其它合适的方法,按患者每千克的体重0.1-1000mg的剂量给予病人。活性成分可以一次性服用,或者可以分成较小剂量在预定的间隔服用,比如每天一次或每两天一次。应该了解的是,上面提到的剂量范围只是示范性的,而并不是想限制本发明的范围。活性化合物的有效治疗剂量可能根据各种因素而不同,这些因素包括但不仅限于,所使用化合物的活性、患者体内活性化合物的稳定性、所要缓解的病症的严重程度、所治疗患者的总体重、给药的途径、活性化合物在患者体内吸收的容易程度、分布、排泄,所治疗患者的年龄和敏感度等等,这些对技术人员来所都是显而易见的。摄入量可因各种因素随着时间变化而调整。
根据本发明,提供了一种反式-[四氯双(1H-吲唑)钌(III)]或其药学上可接受的盐,比如反式-[四氯双(1H-吲唑)钌(III)]碱金属盐(例如:钠反式-[四氯双(1H-吲唑)钌(III)]或反式-[四氯双(1H-吲唑)钌(III)])钾盐在制备一种可以用于治疗胃癌的药物中的应用。这种药物可以是注射型,例如适合于静脉注射、皮下注射或肌肉注射给药。注射剂型比如缓冲溶液或悬浮液在本技术领域内众所周知。
依据本发明的另一个方面,提供了一种医药试剂盒,包括一个容器里的一个单位剂型的反式-[四氯双(1H-吲唑)钌(III)]或其一种药学上可接受的盐,比如碱金属盐的反式-[四氯双(1H-吲唑)钌(III)](例如:反式-[四氯双(1H-吲唑)钌(III)]钠盐或反式-[四氯双(1H-吲唑)钌(III)]钾盐;也可以还包括根据本发明方法的试剂盒使用说明书,例如治疗、预防胃癌或延迟胃癌的发作,或者是预防或延缓胃癌,或治疗抵抗性胃癌。对技术人员来说显而易见,单元剂型的治疗化合物的剂量由本发明方法中使用于患者的剂量决定的。在试剂盒中,反式-[四氯双(1H-吲唑)钌(III)]或其药学上可接受的盐,比如反式-[四氯双(1H-吲唑)钌(III)]碱金属盐(反式-[四氯双(1H-吲唑)钌(III)]钠盐或反式-[四氯双(1H-吲唑)钌(III)])钾盐可以是以冻干的形式,每瓶按25mg单位的剂量。在临床中,按照本发明溶解冻干形式给需要治疗的患者施用。
例1
要测试反式-[四氯双(1H-吲唑)钌(III)]钠盐的活性,采用人胃癌细胞株NCI-87(分化性腺癌)进行ATCC的MTT细胞增殖试培养原种培养物使达到70-80%细胞覆盖。在体外使用ATCC的MTT细胞增殖测定(目录标号:30-1010K)来评价指定细胞系的反式-[四氯双(1H-吲唑)钌(III)]钠盐的抗增殖的活性。使用RPMI1640(Cell Gro10-040-CV)使NCI-N87生长,同时用1%的1M的HEPES、1%的丙酮酸钠、1%的45%葡萄糖溶液、10%的热灭火FBS和1%的聚萘二甲酸乙二醇酯/生长链球菌/谷氨酰胺。NCI-N87被接种到20E+03细胞/孔的细胞板,并用1,000μM或是它的(250μM、62.5μM等等)一系列的4X稀释液的反式-[四氯双(1H-吲唑)钌(III)]钠处理。在处理72小时后,100μl培养基从每孔处移走,并在每孔中加入10μl的MTT试剂。细胞板在37℃下培养4小时,然后加入100μl的洗涤剂。细胞板在黑暗中在室温下放置过夜,并使用Pro(5.2版,MolecularDevices公司)在读板仪上读取。
吸光度数据分析如下:使用专业版(版本5.2,Molecular Devices公司)把吸光度值转换为对照百分比,并绘制针对测试剂的浓度曲线用于IC50计算。在计算对照百分比之前减去所有孔中的细胞板空白信号平均数。通过区分无药物对照平均数(色谱柱11的值;细胞+对照载体)再乘以100的每个测试孔的吸光度值来计算对照百分比值。使用4参数方程获得IC50值和其他参数,分析对照化合物浓度曲线与百分比相对来描述S型剂量反应曲线。
通过使用以下四参数逻辑方程曲线拟合数据来估算待测化合物的IC50值:
其中“Top”是相对于对照吸光度(100%)的最大百分比(图1中的“A”值),“Bottom”是在化合物浓度最高时相对于对照吸光度的最小百分比(图1中的“D”值),Y是对照吸光度,X是测试药剂浓度,IC50是化合物抑制细胞生长达到对照细胞的50%时的浓度(图1中的“C”值),n是曲线的斜率(图1中的“C”值)。在NCI-N87的细胞系中钠反式-[四氯双(1H-吲唑)钌(III)]的IC50是3.73μM。
说明书中提及的所有论文和专利申请书是领域内技术人员对本发明相关的认识水平的体现。所有的论文和专利申请书在此通过相同程度的引用结合到文中,好像每篇单个的论文或专利申请书都是特定的和单独的提及而通过引用结合到文中。论文和专利申请书的仅仅提及不一定表示承认它们是相对于本申请的在先技术。
尽管前述的发明为了清楚的理解通过图示和例子的方式而描述的相当详细,但显然一些改变和修正可能在附加的权利要求范围内实行。
Claims (6)
1.反式-[四氯双(1H-吲唑)钌(III)]的药学上可接受的盐在制备用于胃癌治疗、预防或延缓的药物中的应用。
2.权利要求1之应用,其中所述盐是一种反式-[四氯双(1H-吲唑)钌(III)]碱金属盐。
3.权利要求1之应用,其中所述药学上可接受反式-[四氯双(1H-吲唑)钌(III)]的盐是反式-[四氯双(1H-吲唑)钌(III)]钠盐。
4.治疗胃癌的方法,包括:诊断患者有胃癌;并且用有效剂量的药学上可接受的反式-[四氯双(1H-吲唑)钌(III)]的盐治疗患者。
5.权利要求4之应用,其中所述的盐是反式-[四氯双(1H-吲唑)钌(III)]碱金属盐。
6.权利要求4之应用,其中所述医学上可接受的盐是反式-[四氯双(1H-吲唑)钌(III)]钠盐。
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4843069A (en) * | 1984-07-24 | 1989-06-27 | Asta Pharma Ag | Medicament formulations containing ruthenium compounds with an antitumoral action |
CN101677572A (zh) * | 2007-06-11 | 2010-03-24 | 尼基制药公司 | 制备钌络合物的方法 |
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JP2013531064A (ja) * | 2010-07-17 | 2013-08-01 | ニッキ ファーマ インク. | 難治性癌を治療する方法 |
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WO2012068319A2 (en) * | 2010-11-17 | 2012-05-24 | Niiki Pharma Inc. | Method of treating hematological cancers |
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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CN101677572A (zh) * | 2007-06-11 | 2010-03-24 | 尼基制药公司 | 制备钌络合物的方法 |
Non-Patent Citations (2)
Title |
---|
CLYDE A. SMITH等: "Binding of ruthenium(III) anti-tumor drugs to human lactoferrin probed by high resolution Xray crystallographic structure analyses", 《JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY》 * |
S. KAPITZA等: "Heterocyclic complexes of ruthenium(III) induce apoptosis in colorectal carcinoma cells", 《JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY》 * |
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