CN1254282A - 治疗病毒感染和癌的苯并咪唑-2-氨基甲酸酯 - Google Patents
治疗病毒感染和癌的苯并咪唑-2-氨基甲酸酯 Download PDFInfo
- Publication number
- CN1254282A CN1254282A CN97182190A CN97182190A CN1254282A CN 1254282 A CN1254282 A CN 1254282A CN 97182190 A CN97182190 A CN 97182190A CN 97182190 A CN97182190 A CN 97182190A CN 1254282 A CN1254282 A CN 1254282A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- benzimidizole derivatives
- cancer
- following structure
- tumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
本发明公开了在哺乳动物上抑制肿瘤和癌生长、并可用于治疗病毒感染的含杀真菌剂的药物组合物。所用的特定杀真菌剂是具有式(Ⅰ)的苯并咪唑衍生物、其药学上可接受的盐或其混合物:其中,R选自H、羧基(-CO2H)、羟基、氨基或酯基(-CO2R’),其中R’选自烷基、卤代烷基、链烯基和环烷基,其中烷基具有1—8个碳原子,或CH3CH2(OCH2CH2)n,或CH3CH2CH2(OCH2CH2CH2)n或(CH3)2CH(OCH(CH3)CH2)n-;其中n为1—3。
Description
技术领域
本发明是有效地治疗HIV和其它病毒感染和抑制癌和在哺乳动物(特别是人和温血动物)中肿瘤生长的药物组合物。此组合物包含苯并咪唑衍生物,其药学上可接受的盐或与其它病毒和癌治疗剂的混合物。
发明背景
HIV和其它病毒感染是主要死因。HIV是病毒在体内复制、攻击机体免疫系统的一种疾病。HIV病毒不易被摧毁,也没有好的机制使宿主细胞不复制病毒。单纯性疱疹是难以治愈(即使并非不可能)的另一种病毒感染。人们迫切期待治疗这些疾病和其它病毒感染的方法。显然,能靶向HIV病毒和抑制病毒复制的物质是极吸引人的。
癌是动物和人的主要死因。癌的确切病因不明,但是很多研究者已证明某些活动如吸烟或暴露于致癌剂与某些类型癌和肿瘤的发病率之间的联系。
很多类型化疗剂已证明对癌和肿瘤细胞有效,但并非所有类型的癌和肿瘤对这些化疗剂产生反应。不幸的是这些药物中很多也损伤正常细胞。这些化疗剂的确切作用机制并非总是明了的。
尽管癌治疗领域有所进展,但迄今最主要的治疗是手术、放射和化学治疗。化学治疗被认为是对付已转移的癌或特别有侵袭性的癌。这样的杀细胞剂或细胞抑制剂对生长指数高的癌即其细胞迅速分裂的癌作用最好。迄今,激素(特别是雌激素、孕酮和睾酮)、各种微生物产生的一些抗生素、烷化剂和抗代谢剂形成了肿瘤学家可利用的治疗的主体。对癌和肿瘤细胞有特异性而不影响正常细胞的理想的细胞毒剂将是特别令人满意的。不幸的是,并未发现这样的细胞毒剂,人们使用的是针对分裂特别快的细胞(肿瘤和正常细胞)的替代药物。
显然,因对肿瘤细胞有独特特异性而针对肿瘤细胞的物质的开发将是一个突破点。或者,对肿瘤细胞有细胞毒性而对正常细胞显示轻微作用的物质将是令人满意的。因此,本发明的目的是提供有效抑制哺乳动物肿瘤和癌生长而对正常细胞作用小或无作用的药物组合物。
更具体地说,本发明的目的是提供包含本文所限定的药物载体和苯并咪唑衍生物的抗癌药物组合物及治疗这些癌症的方法。
这些组合物对于病毒也有效,可用于治疗病毒感染。因此,本发明的另一个目的是提供治疗诸如HIV、流感和鼻病毒的病毒感染的方法。
从下面的本发明详细描述中,这些和其它的目的会变得明显起来。
发明概述
治疗哺乳动物特别是温血动物和人的病毒感染和癌症的药物组合物,包含药物载体和有效量的下式所示化合物或其药学上可接受的无机或有机酸盐或其混合物:其中,R选自H、羧基(-CO2H)、羟基、氨基或酯基(-CO2R′),其中R′选自烷基、卤代烷基、链烯基和环烷基,其中烷基具有1-8个碳原子,或CH3CH2(OCH2CH2)n,或CH3CH2CH2(OCH2CH2CH2)n或(CH3)2CH-,及和(OCH(CH3)CH2)n-,其中n为1-3。较佳的烷基是直链的。卤素以在末端碳上取代、并以氯为佳。较佳的环烷基具有3-6个碳原子。环烷基还包括在烷基链上取代的环烷基,2-环丙基乙基、环丙基甲基、2-环丙基丙基或2-环丙基丙基或环己基甲基。较佳的化合物具有如下结构式:和和和和
通过将有效量经口服、直肠内、局部或胃肠外、静脉使用或直接注射进肿瘤,这些组合物可用于抑制人体或动物体内癌和其它肿瘤的生长。
发明的详述
A.定义:
本文中,术语“包含”表示各种成分可合用于本发明的药物组合物。因此,术语“主要由...组成”和“由...组成”包含在术语“包含”中。
本文中,“药学上可接受的”成分是适用于人和/或动物而无过度不良反应(如毒性、刺激和变态反应)即有合理的效益/风险比的物质。
本文中,术语“安全有效量”指按本发明的方式使用时足以获得需要的治疗反应而无过度不良反应(如毒性、刺激和变态反应)即有合理的效益/风险比的成分的量。显然,具体的“安全有效量”因各种因素而异,如受治疗的特殊病情、患者的身体条件、受治疗的哺乳动物的种类、疗程、同时进行的治疗的种类(如果有的话)、所应用的具体制剂和化合物或其衍生物的结构。
本文中,“药物加成盐”是抗癌化合物与有机或无机酸的盐。较佳的这些酸加成盐为氯化物、溴化物、硫酸盐、硝酸盐、磷酸盐、磺酸盐、甲酸盐、酒石酸盐、马来酸盐、苹果酸盐、柠檬酸盐、苯甲酸盐、水杨酸盐、抗坏血酸盐等。
本文中,“药物载体”是用于将抗癌剂传送给动物或人的药学上可接受的溶剂、悬浮剂或赋形剂。载体可以是液体或固体,是按计划的给药方式而选择的。
本文中,“癌”指在哺乳动物中发现的所有类型的癌或赘生物或恶性肿瘤(包括白血病)。
本文中,“抗癌化合物”是苯并咪唑衍生物及其盐。确切的苯并咪唑衍生物在下面详细描述。
本文中,“化疗剂”包括与DNA作用的药物、抗代谢剂、与微管蛋白作用的药物、激素类制剂和其它药剂,如天冬酰胺酶或羟基脲。
本文中,“病毒”包括在人或其它温血动物引起疾病(病毒感染)的病毒,诸如HIV病毒、疱疹、流感和鼻病毒等。
本文中,“增效剂”为曲普利啶及其顺式异构体或丙考达唑,它们与化疗剂和除草剂或杀真菌剂合并使用。
本文中,“明显减小”表示瘤块减小的量明显。通常小于原来瘤块的50%,较佳为瘤块减小到不可检出的量。
B.抗癌和抗病毒化合物
抗癌化合物是苯并咪唑衍生物。这些衍生物具有如下结构,及其药学上可接受的无机或有机加成盐:其中,R选自H、羧基(-CO2H)、羟基、氨基或酯基(-CO2R′),其中R′选自烷基、卤代烷基、链烯基和环烷基,其中烷基具有1-8个碳原子,或CH3CH2(OCH2CH2)n,或CH3CH2CH2(OCH2CH2CH2)n或(CH3)2CH(OCH(CH3)CH2)n-,其中n为1-3。较佳的烷基是直链的。卤素以在末端碳上取代、并以氯为佳。较佳的环烷基具有3-6个碳原子。环烷基还包括在烷基链上取代的环烷基,2-环丙基乙基、环丙基甲基、2-环丙基丙基或2-环丙基丙基或环己基甲基。较佳的化合物具有如下结构式:和和和和和
C.HIV药物
用两大类药物(逆转录酶抑制剂和蛋白酶抑制剂)治疗HIV。AZT广泛用于治疗急性HIV。除草剂和杀真菌剂及其衍生物可与AZT合用于治疗急性HIV。它们并不干扰AZT的活性。
其它HIV药物和抗病毒剂可与本发明提供的治疗一起使用。这些药物包括逆转录酶抑制剂和蛋白酶抑制剂。这些药物可与除草剂或杀真菌剂同时使用或相继给药。
D.化疗剂
杀真菌剂和除草剂可与化疗剂合用。可以是相继的,用化疗剂使肿瘤变小,然后开始用除草剂或杀真菌剂进行治疗,或两种材料可一起给药。
化疗剂一般被分成与DNA-作用的药物、抗代谢物、与微管蛋白作用的药物、激素类药和其他药物如天冬酰胺酶或羟基脲等类。每类化疗剂可根据化合物或活性的类型而被进一步细分。可以相继给药的方法与除草剂或杀真菌剂合并使用的化疗剂主要包括与DNA-作用的药物、抗代谢物、与微管蛋白作用的药物这些类的成员。对于化疗剂及其给药方法的详细论述,参见Dorr等,癌症化疗手册(CancerChemotherapy Handbook),第2版,第15-34页,Appleton & Lange(Connecticut,1994),该文献在此引用作为参考。
为了减小肿瘤块或阻止癌细胞生长,化疗剂必须阻止细胞复制,还必须干扰细胞自我维持的能力。起这些作用的药物主要是顺铂之类与DNA-作用的药物及与微管蛋白作用的药物。
与DNA作用的药物包括烷化剂,如顺铂、环磷酰胺、六甲蜜胺;DNA链断裂剂,如博来霉素;嵌入型拓扑异构酶II抑制剂,如放线菌素D和阿霉素;非嵌入型拓扑异构酶II抑制剂,如依托泊甙和替尼泊甙;以及DNA小沟结合剂普卡霉素(Plcamydin)。
烷化剂与细胞DNA、RNA和蛋白质分子,以及与更小的氨基酸、谷胱甘肽及类似化学物质形成共价的化学加合物。一般,这些烷化剂与细胞组分中的亲核原子反应,如在核酸、蛋白质、氨基酸或谷胱甘肽中的氨基、羧基、磷酸根、巯基。这些烷化剂在癌症治疗中的机制和作用还不十分了解。典型的烷化剂包括:
氮芥类,如苯丁酸氮芥、环磷酰胺、异环磷酰胺、氮芥(Mechlorethamine)、美法仑、乌拉莫司汀;
氮丙啶类如塞替派;
甲磺酸酯类如白消安;
亚硝脲类,如卡莫司汀、洛莫司汀、链佐星;
铂复合物类,如顺铂、卡铂;
生物还原烷化剂(alkylator),如丝裂霉素和丙卡巴肼、达卡巴嗪和六甲蜜胺;
DNA链断裂剂包括博来霉素;
DNA拓扑异构酶II抑制剂包括下列类型:
嵌入剂,如安吖啶、放线菌素D、柔红霉素、阿霉素、伊达比星和米托蒽醌;
非嵌入剂,如依托泊甙和替尼泊甙。
DNA小沟结合剂是普卡霉素。
抗代谢物通过两种主要机制中的一种或另一种而干扰核酸的产生。某些药物可抑制DNA合成的直接前体脱氧核苷三磷酸的产生,从而抑制DNA复制。某些化合物与嘌呤或嘧啶足够相象,从而可在核苷酸合成途径中代替它们。随后,这些类似物可代替正常的组分而进入DNA和RNA。可用于本发明的抗代谢物包括:
叶酸拮抗剂,如氨甲蝶呤和三甲曲沙;
嘧啶拮抗剂,如氟尿嘧啶、脱氧氟尿苷、CB3717、阿扎胞苷、阿糖胞苷、和氟尿苷;
嘌呤拮抗剂包括巯嘌呤、6-硫鸟嘌呤、氟达拉滨、喷司他丁;
糖修饰的类似物包括Cyctrabine、氟达拉滨;
核糖核苷酸还原酶抑制剂包括羟基脲。
与微管蛋白作用的药物通过结合于微管蛋白(一种可聚合形成细胞微管的蛋白质)的特异位点而起作用。微管是关键的细胞结构单元。当作用的药物结合于该蛋白质时,细胞不能形成微管。与微管蛋白作用的药物包括长春新碱和长春碱(两者都是生物碱),以及紫杉醇。
肾上腺皮质类甾醇类衍生自天然的肾上腺皮质醇或氢化可的松。可以使用它们,因为它们有消炎的优点而且某些能够抑制有丝分裂并抑制DNA合成。这些化合物包括:泼尼松、地塞米松、甲泼尼松龙和泼尼松龙。
羟基脲似乎主要通过抑制核糖核苷酸还原酶而起作用。
天冬酰胺酶是一种将天冬酰胺转变成无功能的天冬氨酸从而阻断肿瘤中蛋白质合成的酶。
激素类药物和黄体生成激素不常用于实质上减小肿瘤块。但是,它们可与化疗剂或除草剂或杀真菌剂合用。
激素阻断药也可用于治疗癌和肿瘤。它们可用于激素敏感性肿瘤,并且通常是从天然来源衍生。它们包括:
雌激素、结合雌激素和炔雌醇和己烯雌酚、氯烯雌醚和Idenestrol;
孕激素类,如己酸羟孕酮、甲羟孕酮和甲地孕酮;
雄激素类,如睾酮、丙酸睾酮、氟甲睾酮、甲睾酮;
促黄体生成激素释放激素类药或促性腺激素释放激素拮抗剂,主要被用于治疗前列腺癌。其中包括乙酸亮丙瑞林和乙酸戈舍瑞林。它们抑止睾丸生物合成类固醇。
抗激素类药包括:
抗雌激素剂如他莫昔芬(Tamosifen);
抗雄激素剂如氟他胺;和
抗肾上腺剂如米托坦和氨鲁米特。
E.增效剂
“增效剂”可以是任何这样的物质,它能提高或增加药物组合物的效力和/或作用于免疫系统。一种这样的增效剂是曲普利啶及其顺式异构体,它们可与化疗剂和杀真菌剂或除草剂合并使用。曲普利啶在US 5,114,951(1992)中有描述。另一种增效剂是丙考达唑,1H-苯并咪唑-2-丙酸;[β-(2-苯并咪唑)丙酸;2-(2-羧乙基)苯并咪唑;丙帕唑(propazol)]。丙考达唑是一种针对病毒和细菌感染的非特异的活性免疫保护剂,它可与此处所述的组合物一起使用。
增效剂可改善除草剂或杀真菌剂化合物的效能并可以安全有效量使用。这些联合使用可经口服给药、直肠内给药、局部给药或胃肠外给药法投药给患者或动物。
抗氧化维生素如抗坏血酸、β-胡萝卜素、维生素A和维生素E可与本发明组合物一起投药。
F.剂量
任何合适的剂量都可用于本发明方法。化合物和载体的类型以及数量可以很不相同,这取决于温血动物或人的种类、体重和待治疗的肿瘤。一般,合适的剂量是少至约2毫克(mg)/公斤(kg)体重,多至约4000毫克(mg)/公斤(kg)体重。较佳地,使用15毫克/公斤体重到多至约1500毫克/公斤体重。对于化疗剂,从约0.01毫克/公斤体重至约400毫克/公斤体重的较低剂量是可接受的,尽管高达1500mg/kg的量也可使用。可按本发明方法给予合适的剂量以治疗HIV。化合物和载体的种类及量可根据温血动物或人的种类而有很大差异。杀真菌剂或除草剂及其衍生物的范围和比例以及所用的HIV治疗剂因药物种类而异。一般来说,除草剂或杀真菌剂及其衍生物的剂量以低至约2mg/kg体重、高至约4000mg/kg体重为宜。更高的剂量(高达6000mg/kg体重)也可使用。除草剂或杀真菌剂以使用从15mg/kg体重至高达约3000mg/kg体重水平为宜。一般,给人的剂量低于给小温血动物如小鼠的剂量。剂量单位包括一种化合物,或者该化合物与其他化合物或其他抑制癌症的化合物形成的混合物。对于HIV药物,可用约0.01mg/kg体重至高达1500mg/kg体重。一般,给人的剂量低于给小温血动物如小鼠的剂量。剂量单位包括一种化合物,或者该化合物与其他化合物或其他抑制癌症的化合物形成的混合物。剂量单位还可含有稀释剂、填充剂(extender)、载体等。剂量单位可为固体或凝胶形式,如丸剂、片剂、胶囊剂等,或者是液体形式,它们适合口服给药、直肠给药、局部给药、静脉内注射或肠胃外给药,或者注射在肿瘤部位或其周围。
G.释药剂型
抗癌化合物一般与药物上可接受的载体混合。载体可以是固体、液体,一般根据所用的给药方式而选择类型。活性药物可以以片剂或胶囊、或作为附聚的粉末,或者以液体形式一起给药。合适固体载体的例子包括:乳糖、蔗糖、明胶和琼脂。胶囊或片剂可以容易地制备,并且便于吞咽或咀嚼;其他的固体形式包括颗粒和疏松粉末(bulk powder)。片剂可含有适当的粘合剂、润滑剂、稀释剂、崩解剂、着色剂、调味剂、流动诱导剂(flow-inducing agent)和助熔剂(melting agent)。合适的液体剂型的例子包括:在水、药物上可接受的脂肪和油、醇或其他有机溶剂(包括酯)中的溶液或悬浮液,乳剂、糖浆、酏剂、悬浮液、用非泡腾颗粒再生的溶液和/或悬浮液、以及用泡腾颗粒再生的泡腾制剂。这样的液体剂型可含有,例如,适当的溶剂、防腐剂、乳化剂、悬浮剂、稀释剂、甜味剂、增稠剂和助熔剂。口服剂型可任意含有调味剂和着色剂。肠胃外和静脉内给药的剂型还可含有矿物质和其他物质,以便使它们与注射或所选的释药系统类型相配伍。
可用于配制本发明口服剂型的、具体的药物上可接受的载体和赋形剂的例子,在美国专利No.3,903,297(1975年9月2日授予Robert)中有描述。用于制造本发明的有用剂型的技术和组合物,在下列文献中有描述:7种现代药剂(7Modern Pharmaceutics).第9和10章(Banker & Rhodes编,1979);Lieberman等,药物剂型:片剂(Pharmaceutical Dosage Forms:Tablets)(1981);和Ansel,药物剂型导论(Introduction to Pharmaceutical Dosage Forms)第2版(1976)。
H.治疗方法
治疗方法可以是,在治疗待治疗的具体病毒、癌或肿瘤类型时任何适当的有效的方法。治疗可以是口服给药、直肠给药、局部给药、肠胃外给药、静脉内给药、或者注射在肿瘤部位或其周围。施用或给予有效量药物的方法依据待治疗的肿瘤或病毒而有所不同。常采用静脉内、皮下或肌内施用与合适的载体一起配制的苯并咪唑衍生物的肠胃外治疗方法。在癌症治疗中,另外的抗病毒物质可与苯并咪唑衍生物一起使用,另外的抑制癌症化合物也可合用。可用稀释剂促进施用或给药,这是将化合物投予温血动物的较佳方法。
治疗病毒感染,将苯并咪唑衍生物多剂给药7至约21天,如果需要还可更长些,以抑制生长或杀灭病毒。在慢性感染的情况下,这些药物可能需要延长给药时间,可长达数年。
治疗急性病毒感染或HIV,苯并咪唑衍生物可在AZT治疗后给予或与其它HIV治疗一起进行。这些药物可以顺序给药方案给药,在该方案中首先减少体内HIV病毒,然后给予苯并咪唑衍生物使病毒不继续复制。在用苯并咪唑衍生物治疗过程中可继续进行AZT治疗。如果疾病在早期阶段,可给予苯并咪唑衍生物使病毒不再复制或生长,从而减慢疾病的进展。
在癌症治疗中,较佳为先给予苯并咪唑衍生物以明显地减小癌或肿瘤块的大小。通常这需要3至约14天。肿瘤或癌细胞水平的减小可达到小于原来水平的50%。放射治疗可与苯并咪唑衍生物治疗合用。
一旦肿瘤减小,立即给予苯并咪唑衍生物。由于该物质相对安全,如果需要,可给药14天至365天,以保持其在减少癌重新生长上的有效性。
下列实施例是阐述性的,并不意味着对本发明的限制。
实施例1
对下面每一个化合物测试溶解性,用MTT试验测抗B16小鼠黑素瘤和HT29的生长抑制作用,报告为IC50(μM),对微管蛋白聚合的抑制作用,及用甲基绿置换测定与小牛胸腺DNA的间接结合。得到如下结果:
B16(小鼠黑素瘤) 4.925
HT29(人结肠癌) 3.297
B16(小鼠黑素瘤) 0.0844
B16(小鼠黑素瘤) 0.112
B16(小鼠黑素瘤) 0.0440
B16(小鼠黑素瘤) 0.0621
Claims (12)
2.如权利要求1所述的药物组合物,包含药学上可接受的载体和安全有效量的苯并咪唑衍生物。
7.如权利要求2所述的药物组合物,其中所述苯并咪唑衍生物具有如下结构:
9.如权利要求1、2、3、4、5、6、7或8所述的药物组合物,其中所述药学上可接受的酸加成盐选自氯化物、溴化物、硫酸盐、硝酸盐、磷酸盐、磺酸盐、甲酸盐、酒石酸盐、马来酸盐、苹果酸盐、柠檬酸盐、苯甲酸盐、水杨酸盐、抗坏血酸盐及其混合物。
10.治疗温血哺乳动物病毒感染的方法,其特征在于:投予安全有效量的如权利要求1、2、3、4、5、6、7、8或9所述的药物组合物。
11.治疗癌或肿瘤的方法,其特征在于:投予安全有效量的如权利要求1、2、3、4、5、6、7、8或9所述的药物组合物。
12.如权利要求11所述的方法,其中化疗剂与所述药物组合物合用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/857,811 US6506783B1 (en) | 1997-05-16 | 1997-05-16 | Cancer treatments and pharmaceutical compositions therefor |
US08/857,811 | 1997-05-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1254282A true CN1254282A (zh) | 2000-05-24 |
Family
ID=25326784
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN97182190A Pending CN1254282A (zh) | 1997-05-16 | 1997-11-26 | 治疗病毒感染和癌的苯并咪唑-2-氨基甲酸酯 |
Country Status (22)
Country | Link |
---|---|
US (13) | US6506783B1 (zh) |
EP (1) | EP0956017B1 (zh) |
JP (1) | JP2001527523A (zh) |
KR (1) | KR20000049065A (zh) |
CN (1) | CN1254282A (zh) |
AR (1) | AR010008A1 (zh) |
AT (1) | ATE363904T1 (zh) |
AU (1) | AU728690B2 (zh) |
BR (1) | BR9714634A (zh) |
CA (1) | CA2268840C (zh) |
CZ (1) | CZ125299A3 (zh) |
DE (1) | DE69737793D1 (zh) |
HU (1) | HUP0001170A3 (zh) |
IL (1) | IL129352A0 (zh) |
NO (1) | NO991700L (zh) |
NZ (1) | NZ335159A (zh) |
PE (1) | PE11099A1 (zh) |
PL (1) | PL335541A1 (zh) |
SK (1) | SK47099A3 (zh) |
TR (1) | TR199901528T2 (zh) |
WO (1) | WO1998051304A1 (zh) |
ZA (1) | ZA979096B (zh) |
Families Citing this family (68)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6479526B1 (en) | 1995-04-12 | 2002-11-12 | The Procter & Gamble Company | Pharmaceutical composition for inhibiting the growth of viruses and cancers |
US6262093B1 (en) | 1995-04-12 | 2001-07-17 | The Proctor & Gamble Company | Methods of treating cancer with benzimidazoles |
US6177460B1 (en) | 1995-04-12 | 2001-01-23 | The Procter & Gamble Company | Method of treatment for cancer or viral infections |
US5770616A (en) | 1995-06-07 | 1998-06-23 | The Procter & Gamble Company | Pharmaceutical composition for inhibiting the growth of cancers |
US6265427B1 (en) | 1995-06-07 | 2001-07-24 | The Proctor & Gamble Company | Pharmaceutical composition for the method of treating leukemia |
US6686391B2 (en) | 1995-08-04 | 2004-02-03 | University Of Arizona Foundation | N-chlorophenylcarbamate and N-chlorophenylthiocarbamate compositions |
US5900429A (en) | 1997-01-28 | 1999-05-04 | The Procter & Gamble Company | Method for inhibiting the growth of cancers |
US6506783B1 (en) | 1997-05-16 | 2003-01-14 | The Procter & Gamble Company | Cancer treatments and pharmaceutical compositions therefor |
US6245789B1 (en) | 1998-05-19 | 2001-06-12 | The Procter & Gamble Company | HIV and viral treatment |
US6423734B1 (en) * | 1999-08-13 | 2002-07-23 | The Procter & Gamble Company | Method of preventing cancer |
US6384049B1 (en) * | 2000-05-25 | 2002-05-07 | The Procter & Gamble Company | Cancer treatment |
US6608096B1 (en) * | 2000-09-26 | 2003-08-19 | University Of Arizona Foundation | Compounds and methods for use thereof in the treatment of cancer or viral infections |
US6380232B1 (en) | 2000-09-26 | 2002-04-30 | The Procter & Gamble Company | Benzimidazole urea derivatives, and pharmaceutical compositions and unit dosages thereof |
US6407105B1 (en) * | 2000-09-26 | 2002-06-18 | The Procter & Gamble Company | Compounds and methods for use thereof in the treatment of cancer or viral infections |
US6462062B1 (en) * | 2000-09-26 | 2002-10-08 | The Procter & Gamble Company | Compounds and methods for use thereof in the treatment of cancer or viral infections |
WO2002041891A2 (en) * | 2000-11-01 | 2002-05-30 | The Procter & Gamble Company | Hiv treatment with benzimidazoles |
DE60117858T2 (de) * | 2000-12-07 | 2006-11-30 | Universiteit Utrecht Holding B.V. | Zusammensetzung zur behandlung von entzündlichen erkrankungen |
CA2434654A1 (en) | 2001-01-11 | 2002-09-06 | Board Of Regents, The University Of Texas System | Antihelminthic drugs as a treatment for hyperproliferative diseases |
US6515074B2 (en) * | 2001-01-22 | 2003-02-04 | Delphi Technologies, Inc. | Thermoplastic polymer alloy compositions and process for manufacture thereof |
US6693125B2 (en) * | 2001-01-24 | 2004-02-17 | Combinatorx Incorporated | Combinations of drugs (e.g., a benzimidazole and pentamidine) for the treatment of neoplastic disorders |
AUPR626001A0 (en) * | 2001-07-10 | 2001-08-02 | Mcgregor, Neil | A method of treatment and/or prophylaxis |
AU2002330088B2 (en) * | 2001-09-24 | 2009-09-03 | Jessie L.-S. Au | Methods and compositions to determine the chemosensitizing dose of suramin used in combination therapy |
CA2478470A1 (en) * | 2002-03-26 | 2003-10-09 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Solubilization of weak bases |
US20050152962A1 (en) * | 2002-06-12 | 2005-07-14 | Metselaar Josbert M. | Composition for treatment of inflammatory disorders |
US8492443B2 (en) * | 2002-07-08 | 2013-07-23 | Joe S. Wilkins, Jr. | Treatment for herpes simplex virus and other infectious diseases |
EP1393720A1 (en) * | 2002-08-27 | 2004-03-03 | Universiteit Utrecht | Vesicle-encapsulated corticosteroids for treatment of cancer |
AU2003900064A0 (en) * | 2003-01-09 | 2003-01-23 | Penam Investments Pty. Ltd. | A method of treatment or prophylaxis of viral infection. |
KR20050122210A (ko) * | 2003-03-17 | 2005-12-28 | 다케다 샌디에고, 인코포레이티드 | 히스톤 탈아세틸화 효소 억제제 |
EP1598353A1 (en) * | 2004-05-17 | 2005-11-23 | Boehringer Ingelheim International GmbH | Pyrrolobenzimidazolones and their use as antiproliferative agents |
JP2008515956A (ja) * | 2004-10-12 | 2008-05-15 | ノボ ノルディスク アクティーゼルスカブ | 11β−ヒドロキシステロイドデヒドロゲナーゼ1型活性スピロ化合物 |
US7193254B2 (en) * | 2004-11-30 | 2007-03-20 | International Business Machines Corporation | Structure and method of applying stresses to PFET and NFET transistor channels for improved performance |
EP1830847B1 (en) * | 2004-12-06 | 2014-11-19 | Pitney Pharmaceuticals Pty Limited | Treatment for cancer |
EP2329841A1 (en) | 2005-02-04 | 2011-06-08 | Survac ApS | Survivin peptide vaccine |
US7265248B1 (en) | 2005-04-29 | 2007-09-04 | Technology Innovations, Llc | Compositions and methods for the treatment of malaria |
KR20080069189A (ko) * | 2005-11-01 | 2008-07-25 | 트랜스테크 파르마, 인크. | 치환된 아미드의 약학적 사용 |
WO2007051810A2 (en) * | 2005-11-01 | 2007-05-10 | Transtech Pharma | Pharmaceutical use of substituted amides |
AU2006312407A1 (en) * | 2005-11-09 | 2007-05-18 | Philera New Zealand Limited | Treatment of mitochondria-related diseases and improvement of age-related metabolic deficits |
EP1991226B1 (en) * | 2006-02-28 | 2013-03-20 | Merck Sharp & Dohme Corp. | Inhibitors of histone deacetylase |
JP2009530346A (ja) * | 2006-03-21 | 2009-08-27 | ハイ ポイント ファーマシューティカルズ,リミティド ライアビリティ カンパニー | メタボリックシンドロームの治療用のアダマンタン誘導体 |
JP2009532418A (ja) | 2006-04-07 | 2009-09-10 | ハイ ポイント ファーマシューティカルズ,リミティド ライアビリティ カンパニー | 11β−ヒドロキシステロイドデヒドロゲナーゼ1型活性化合物 |
US20100003679A1 (en) * | 2006-06-09 | 2010-01-07 | University Of Miami | Assessment of cellular composition and fractional viability and uses thereof |
WO2007144394A2 (en) * | 2006-06-16 | 2007-12-21 | High Point Pharmaceuticals, Llc. | Pharmaceutical use of substituted piperidine carboxamides |
EP1878721A1 (en) * | 2006-07-13 | 2008-01-16 | Novo Nordisk A/S | 4-Piperidylbenzamides as 11-beta-hydroxysteroid dehydrogenase type 1 inhibitors |
CA2657078A1 (en) * | 2006-07-13 | 2008-01-17 | High Point Pharmaceuticals, Llc | 11beta-hydroxysteroid dehydrogenase type 1 active compounds |
JP2010519240A (ja) * | 2007-02-23 | 2010-06-03 | ハイ ポイント ファーマシューティカルズ,リミティド ライアビリティ カンパニー | 11−ベータ−ヒドロキシステロイドデヒドロゲナーゼの阻害剤としての、n−アダマンチルベンズアミド |
US8334305B2 (en) * | 2007-02-23 | 2012-12-18 | High Point Pharmaceuticals, Llc | N-adamantyl benzamides as inhibitors of 11-β-hydroxysteroid dehydrogenase |
CN101679217A (zh) * | 2007-02-23 | 2010-03-24 | 高点制药有限责任公司 | 作为11β-羟基类固醇脱氢酶抑制剂的N-金刚烷基苯甲酰胺 |
US20110003852A1 (en) * | 2007-02-23 | 2011-01-06 | Soren Ebdrup | N-adamantyl benzamides as inhibitors of 11-beta-hydroxysteroid dehydrogenase |
BRPI0721430A2 (pt) * | 2007-03-09 | 2013-01-08 | High Point Pharmaceuticals Llc | amidas indol e benzimidazol como inibidoras de hidroxiesteràide deidrogenase |
EP2141990A4 (en) * | 2007-03-28 | 2011-07-06 | High Point Pharmaceuticals Llc | ACTIVE COMPOUNDS ON 11BETA-HSD1 |
ES2399912T3 (es) * | 2007-04-11 | 2013-04-04 | High Point Pharmaceuticals, Llc | Nuevos compuestos |
CA2685036A1 (en) * | 2007-04-24 | 2008-11-06 | High Point Pharmaceuticals, Llc | Pharmaceutical use of substituted amides |
EP3103791B1 (en) | 2007-06-27 | 2018-01-31 | Merck Sharp & Dohme Corp. | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
CN101808518A (zh) * | 2007-06-27 | 2010-08-18 | 默沙东公司 | 作为组蛋白脱乙酰酶抑制剂的吡啶基和嘧啶基衍生物 |
US8835506B2 (en) | 2008-06-05 | 2014-09-16 | Stc.Unm | Methods and related compositions for the treatment of cancer |
US8771693B2 (en) | 2009-10-27 | 2014-07-08 | Beth Israel Deaconess Medical Center, Inc. | Methods and compositions for the generation and use of conformation-specific antibodies |
WO2012015715A1 (en) | 2010-07-27 | 2012-02-02 | High Point Pharmaceuticals, Llc | Substituted thiazol-2-ylamine derivatives, pharmaceutical compositions, and methods of use as 11-beta hsd1 modulators |
US10487114B2 (en) | 2011-04-27 | 2019-11-26 | Beth Israel Deaconess Medical Center, Inc. | Methods for administering peptides for the generation of effective c/s conformation-specific antibodies to a human subject in need thereof |
NZ721900A (en) | 2012-05-09 | 2018-01-26 | Univ Western Health Sciences | Proliposomal testosterone formulations |
WO2014082085A1 (en) * | 2012-11-26 | 2014-05-30 | The University Of North Carolina At Chapel Hill | Use of itk inhibitors for the treatment of cancer |
WO2016077648A1 (en) * | 2014-11-11 | 2016-05-19 | Neymeyer Calvin E | Method of treating pre-cancerous lesion with glyphosate, and compositions thereof |
WO2016187767A1 (en) * | 2015-05-25 | 2016-12-01 | Hutchison Medipharma Limited | Pharmaceutical compositions and use thereof |
US11547696B2 (en) | 2016-10-28 | 2023-01-10 | Children's Hospital Medical Center | Methods and compositions for treatment of myelodysplastic syndromes and/or acute myeloid leukemias |
CN109633026A (zh) * | 2019-01-03 | 2019-04-16 | 上海市农业科学院 | 一种液相色谱-串联质谱检测多菌灵及其代谢物的方法 |
KR102583547B1 (ko) | 2020-03-30 | 2023-10-06 | (주)바이오메트릭스 테크놀로지 | 신규한 벤지미다졸 유도체, 이의 제조방법 및 이의 항암제 용도 |
EP3907230A1 (en) | 2020-03-30 | 2021-11-10 | Biometrix Technology Inc. | Novel benzimidazole derivatives, preparation method thereof and use thereof as anti-cancer agent comprising the same |
KR102449266B1 (ko) | 2020-06-23 | 2022-09-30 | (주)바이오메트릭스 테크놀로지 | 항암 활성 그리고 항바이러스 활성을 갖는 신규한 벤지미다졸-탄수화물 결합체 화합물(Benzimidazole carbohydrate conjugate compound) 및 이의 제조 방법 |
KR102342313B1 (ko) | 2021-08-27 | 2021-12-24 | (주)바이오메트릭스 테크놀로지 | 벤지미다졸-탄수화물 결합체 화합물을 포함하는 미셀, 이의 제조방법, 이의 항암제 또는 항바이러스제로서의 용도 |
Family Cites Families (96)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE158398C (zh) | ||||
DE136499C (zh) | ||||
US2933502A (en) * | 1958-02-12 | 1960-04-19 | Du Pont | Benzimidazolone derivatives |
US3010968A (en) | 1959-11-25 | 1961-11-28 | Du Pont | Process for manufacture of certain alkyl esters of benzimidazole carbamic acids |
NL134354C (zh) | 1963-05-23 | |||
US3499761A (en) | 1964-07-20 | 1970-03-10 | Gaf Corp | Silver halide emulsions containing alkyl esters of benzimidazole carbamic acid antifogging agents |
BE666795A (zh) | 1964-08-04 | 1966-01-13 | ||
USRE28403E (en) | 1964-08-04 | 1975-04-29 | Butyl and n-propoxy-z-carbo- methoxyaminobenzimidazoles | |
US3541213A (en) | 1966-05-06 | 1970-11-17 | Du Pont | Fungicidal and mite ovicidal substituted 2-aminobenzimidazoles |
US3399212A (en) * | 1966-05-16 | 1968-08-27 | Smith Kline French Lab | Benzimidazole ureas |
US3480642A (en) * | 1967-03-22 | 1969-11-25 | Smithkline Corp | Process for producing 2-carbalkoxyaminobenzimidazoles |
US3881014A (en) | 1968-11-05 | 1975-04-29 | Bayer Ag | N-tritylimidazoles for treating fungal infections |
BE744970A (fr) | 1969-01-28 | 1970-07-27 | Lilly Co Eli | Agents antiviraux et immuno-depresseurs |
BE759337A (fr) | 1969-11-24 | 1971-05-24 | Lilly Co Eli | Benzimidazol (2,1-b)-quinazolin (6h) ones qui sont des immuno-depresseurs, et nouvelles benzimidazo (2,1-b) quinazolin-12-(6h) ones |
FR2046114A5 (en) | 1970-01-30 | 1971-03-05 | Dynachim Sarl | Benzimidazole derivs anthelmintic, antifung - al bactericidal, aericidal, insecticidal, nema |
US3956262A (en) | 1970-12-09 | 1976-05-11 | Beecham Group Limited | Triazenoimidazoles |
US3738995A (en) | 1971-05-14 | 1973-06-12 | Du Pont | Solvent process for the preparation of 1 - carbamoyl-substituted 2 - benzimidazolecarbamates |
DE2144505A1 (de) | 1971-09-06 | 1973-03-15 | Boehringer Sohn Ingelheim | S-triazino- eckige klammer auf 1,2-a eckige klammer zu-benzimidazole |
FR2155888A1 (en) | 1971-10-13 | 1973-05-25 | Agot Aime | Solid anthelmintic composn - for more economical treatment of ruminants |
DE2227919C2 (de) * | 1972-06-08 | 1982-12-23 | Bayer Ag, 5090 Leverkusen | Verfahren zur Herstellung von Benzimidazol-2-yl-carbaminsäure-methylester |
DE2253324A1 (de) | 1972-10-31 | 1974-05-09 | Bayer Ag | 1-alkoxycarbonyl-2- eckige klammer auf bis-(alkoxycarbonyl)-amino eckige klammer zu -benzimidazole, verfahren zu ihrer herstellung, sowie ihre verwendung als fungizide |
US4046906A (en) | 1973-04-21 | 1977-09-06 | Hoechst Aktiengesellschaft | Salts of alkyl 2-benzimidazole-carbamate |
JPS5142565A (en) | 1974-10-09 | 1976-04-10 | Copal Co Ltd | onnoff taimaa |
US4001423A (en) * | 1975-06-20 | 1977-01-04 | Dodds Dale I | 2-(2-ethoxy)ethoxyethyl benzimidazolecarbamate |
DE2527677A1 (de) * | 1975-06-21 | 1977-01-20 | Bayer Ag | Verfahren zur herstellung von 2,4- dioxo-1,2,3,4-tetrahydro-s-triazino- eckige klammer auf 1,2-a eckige klammer zu -benzimidazolen |
US4086235A (en) | 1976-04-12 | 1978-04-25 | Syntex (U.S.A.) Inc. | 5 (6)-Benzene ring substituted benzimidazole-2-carbamate derivatives having anthelmintic activity |
IN159210B (zh) | 1982-01-11 | 1987-04-11 | Council Scient Ind Res | |
IN158878B (zh) | 1982-07-15 | 1987-02-07 | Council Scient Ind Res | |
HU193951B (en) | 1985-03-11 | 1987-12-28 | Richter Gedeon Vegyeszet | Process for producing new sulfur-containing 5-substituted benzimidazol derivatives and pharmaceutical compositions containing them |
US4731366A (en) | 1986-08-05 | 1988-03-15 | Harbor Branch Oceanographic Institution, Inc. | Discorhabdin compositions and their methods of use |
GB2210875B (en) | 1987-10-09 | 1991-05-29 | Farmos Oy | Aromatase inhibiting 4(5)-imidazoles |
US5329012A (en) | 1987-10-29 | 1994-07-12 | The Research Foundation Of State University Of New York | Bis(acyloxmethyl)imidazole compounds |
US5114951A (en) | 1989-04-11 | 1992-05-19 | Burroughs Wellcome Company | Agents for combating multiple drug resistance |
US5149527A (en) | 1990-09-18 | 1992-09-22 | Oncotech, Inc. | Immunopotentiating protocol for chemotherapy-responsive tumors |
US5284662A (en) | 1990-10-01 | 1994-02-08 | Ciba-Geigy Corp. | Oral osmotic system for slightly soluble active agents |
JPH04223274A (ja) | 1990-12-26 | 1992-08-13 | Kansei Corp | 加速度センサ |
GB9106278D0 (en) | 1991-03-25 | 1991-05-08 | Smithkline Beecham Plc | Method of treatment |
US5364875A (en) | 1992-05-11 | 1994-11-15 | The Du Pont Merck Pharmaceutical Company | Imidazoles linked to bicyclic heterocyclic groups for the treatment of atherosclerosis |
US5310748A (en) | 1992-05-11 | 1994-05-10 | The Du Pont Merck Pharmaceutical Company | Imidazoles for the treatment of atherosclerosis |
US5290801A (en) | 1992-05-29 | 1994-03-01 | The Du Pont Merck Pharmaceutical Company | Benzimidazoles for the treatment of atherosclerosis |
KR950702994A (ko) | 1992-08-12 | 1995-08-23 | 로렌스 티. 웰츠 | 탁솔과 복합된, 단백질 키나제 억제제 및 관련 화합물(protein kinase inhibitors and related compounds combined with taxol) |
FR2703057B1 (fr) | 1993-03-24 | 1995-06-16 | Elysees Balzac Financiere | Matériau alvéolaire cellulosique renfermant un agent biocide et procédé pour sa préparation. |
HUT74006A (en) | 1993-03-31 | 1996-10-28 | Merck & Co Inc | Hiv protease inhibitors in pharmaceutical combinations and pharmaceutical compns. contg. them |
US5434163A (en) | 1993-05-14 | 1995-07-18 | The Medical College Of Pennsylvania | Treatment of Cryptococcus neoformans infection |
US5554373A (en) | 1993-11-05 | 1996-09-10 | Seabrook; Samuel G. | Compositions containing anti-microbial agents and methods for making and using same |
JP3213471B2 (ja) | 1994-04-13 | 2001-10-02 | ポーラ化成工業株式会社 | 薬効成分含有リポソーム製剤の製造方法 |
ZA962879B (en) | 1995-04-12 | 1997-03-17 | Procter & Gamble | A pharmaceutical composition for inhibiting the growth of viruses and cancers |
PL322732A1 (en) | 1995-04-12 | 1998-02-16 | Procter & Gamble | Pharmaceutic agent containing n-chlorophenyl carbaminates and n-chlorophenyl thiocarbaminates for inhibiting development of viruses and carcinoma |
US6479526B1 (en) * | 1995-04-12 | 2002-11-12 | The Procter & Gamble Company | Pharmaceutical composition for inhibiting the growth of viruses and cancers |
NZ305784A (en) | 1995-04-12 | 2001-03-30 | Procter & Gamble | Benzimidazole containing medicaments for treating cancers, tumors and viral infections |
US5665713A (en) | 1995-04-12 | 1997-09-09 | Procter & Gamble Company | Pharmaceutical composition for inhibiting the growth of viruses and cancers |
US5656615A (en) | 1995-04-12 | 1997-08-12 | The Procter & Gamble Company | Pharmaceutical composition for inhibiting the growth of cancers and viruses in mammals |
US6262093B1 (en) * | 1995-04-12 | 2001-07-17 | The Proctor & Gamble Company | Methods of treating cancer with benzimidazoles |
US6177460B1 (en) * | 1995-04-12 | 2001-01-23 | The Procter & Gamble Company | Method of treatment for cancer or viral infections |
US5629341A (en) | 1995-04-12 | 1997-05-13 | The Procter & Gamble Company | Pharmaceutical composition for inhibiting the growth of viruses and cancers |
ZA962880B (en) | 1995-04-12 | 1997-03-17 | Procter & Gamble | A pharmaceutical composition for inhibiting the growth of viruses and cancers |
MX9707809A (es) * | 1995-06-07 | 1998-01-31 | Procter & Gamble | Una composicion farmaceutica que contiene bencimidazol para inhibir el crecimiento de canceres. |
SK168697A3 (en) | 1995-06-07 | 1998-12-02 | Procter & Gamble | A medicament for the treatment of leukemia |
US5665751A (en) | 1995-06-07 | 1997-09-09 | The Procter & Gamble Company | Pharmaceutical composition for inhibiting the growth of cancers |
US20010039291A1 (en) * | 1995-06-07 | 2001-11-08 | The Procter & Gamble Company | Compositions and methods of treatment for cancer or viral infections |
US6265427B1 (en) * | 1995-06-07 | 2001-07-24 | The Proctor & Gamble Company | Pharmaceutical composition for the method of treating leukemia |
US6200992B1 (en) * | 1995-06-07 | 2001-03-13 | The Procter & Gamble Company | Pharmaceutical composition for inhibiting the growth of cancers |
US5770616A (en) | 1995-06-07 | 1998-06-23 | The Procter & Gamble Company | Pharmaceutical composition for inhibiting the growth of cancers |
BR9609920A (pt) | 1995-08-03 | 1999-07-06 | Procter & Gamble | Uso de griseofulvina para inibir o crescimento de cânceres |
MX9707808A (es) * | 1995-08-04 | 1998-01-31 | Procter & Gamble | Una composicion farmaceutica que contiene n-clorofenilcarbamatos y n-clorofiniltiocarbamatos para inhibir el crecimiento de virus y canceres. |
CN1195288A (zh) | 1995-08-04 | 1998-10-07 | 普罗克特和甘保尔公司 | 氟康唑抑制癌症生长的用途 |
US6686391B2 (en) * | 1995-08-04 | 2004-02-03 | University Of Arizona Foundation | N-chlorophenylcarbamate and N-chlorophenylthiocarbamate compositions |
US5908855A (en) | 1996-07-16 | 1999-06-01 | The Procter & Gamble Company | Compositions for treating viral infections |
AU6966696A (en) * | 1995-10-05 | 1997-04-28 | Warner-Lambert Company | Method for treating and preventing inflammation and atherosclerosis |
US5627094A (en) * | 1995-12-04 | 1997-05-06 | Chartered Semiconductor Manufacturing Pte, Ltd. | Stacked container capacitor using chemical mechanical polishing |
US6541213B1 (en) * | 1996-03-29 | 2003-04-01 | University Of Washington | Microscale diffusion immunoassay |
DE19623226A1 (de) * | 1996-06-11 | 1997-12-18 | Basf Ag | Katalysatorsysteme vom Typ der Ziegler-Natta-Katalysatoren |
US6056973A (en) * | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
US5825811A (en) | 1997-01-16 | 1998-10-20 | Motorola, Inc. | Method and apparatus for facilitating inbound channel access |
US5900429A (en) * | 1997-01-28 | 1999-05-04 | The Procter & Gamble Company | Method for inhibiting the growth of cancers |
US6506783B1 (en) * | 1997-05-16 | 2003-01-14 | The Procter & Gamble Company | Cancer treatments and pharmaceutical compositions therefor |
PE11499A1 (es) | 1997-05-16 | 1999-03-01 | Procter & Gamble | Tratamiento del hiv y cancer |
US5908885A (en) * | 1997-07-01 | 1999-06-01 | University Of South Alabama | Polysuccinimide and polyaspartate as additives to cementitious materials |
US6245789B1 (en) | 1998-05-19 | 2001-06-12 | The Procter & Gamble Company | HIV and viral treatment |
US6248843B1 (en) * | 1998-09-18 | 2001-06-19 | Mcwhorter Technologies, Inc. | Powder coatings based on branched oligoesters and triazole blocked polyisocyanates |
AU777977B2 (en) | 1998-10-09 | 2004-11-04 | General Mills Inc. | Encapsulation of sensitive liquid components into a matrix to obtain discrete shelf-stable particles |
US6211177B1 (en) * | 1998-11-24 | 2001-04-03 | Cell Pathways, Inc. | Method for treating neoplasia by exposure to substituted 2-aryl-benzimidazole derivatives |
US20010053773A1 (en) * | 1998-12-22 | 2001-12-20 | The Procter & Gamble Company | Method for inhibiting the growth of cancers |
AU2697100A (en) * | 1999-02-23 | 2000-09-14 | Yuhan Corporation | Pharmaceutical capsule compositions containing loratadine and pseudoephedrine |
US6294192B1 (en) | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
US6136835A (en) * | 1999-05-17 | 2000-10-24 | The Procter & Gamble Company | Methods of treatment for viral infections |
US6423734B1 (en) * | 1999-08-13 | 2002-07-23 | The Procter & Gamble Company | Method of preventing cancer |
US6135835A (en) * | 1999-08-16 | 2000-10-24 | Future Beach Corporation | Aquatic vehicle |
US6384049B1 (en) * | 2000-05-25 | 2002-05-07 | The Procter & Gamble Company | Cancer treatment |
US6290929B1 (en) * | 2000-07-28 | 2001-09-18 | The Procter & Gamble Company | Cancer treatment |
US6518269B1 (en) * | 2000-07-28 | 2003-02-11 | University Of Arizona Foundation | Cancer treatment |
US6380232B1 (en) * | 2000-09-26 | 2002-04-30 | The Procter & Gamble Company | Benzimidazole urea derivatives, and pharmaceutical compositions and unit dosages thereof |
US6608096B1 (en) * | 2000-09-26 | 2003-08-19 | University Of Arizona Foundation | Compounds and methods for use thereof in the treatment of cancer or viral infections |
US6407105B1 (en) * | 2000-09-26 | 2002-06-18 | The Procter & Gamble Company | Compounds and methods for use thereof in the treatment of cancer or viral infections |
US6462062B1 (en) * | 2000-09-26 | 2002-10-08 | The Procter & Gamble Company | Compounds and methods for use thereof in the treatment of cancer or viral infections |
WO2002041891A2 (en) * | 2000-11-01 | 2002-05-30 | The Procter & Gamble Company | Hiv treatment with benzimidazoles |
-
1997
- 1997-05-16 US US08/857,811 patent/US6506783B1/en not_active Expired - Fee Related
- 1997-10-10 PE PE1997000897A patent/PE11099A1/es not_active Application Discontinuation
- 1997-10-10 ZA ZA979096A patent/ZA979096B/xx unknown
- 1997-10-17 AR ARP970104815A patent/AR010008A1/es unknown
- 1997-11-26 SK SK470-99A patent/SK47099A3/sk unknown
- 1997-11-26 HU HU0001170A patent/HUP0001170A3/hu unknown
- 1997-11-26 CN CN97182190A patent/CN1254282A/zh active Pending
- 1997-11-26 PL PL97335541A patent/PL335541A1/xx unknown
- 1997-11-26 WO PCT/US1997/021565 patent/WO1998051304A1/en active IP Right Grant
- 1997-11-26 DE DE69737793T patent/DE69737793D1/de not_active Expired - Lifetime
- 1997-11-26 CA CA002268840A patent/CA2268840C/en not_active Expired - Fee Related
- 1997-11-26 JP JP52193098A patent/JP2001527523A/ja not_active Ceased
- 1997-11-26 AU AU74027/98A patent/AU728690B2/en not_active Ceased
- 1997-11-26 AT AT97949600T patent/ATE363904T1/de not_active IP Right Cessation
- 1997-11-26 BR BR9714634-0A patent/BR9714634A/pt unknown
- 1997-11-26 TR TR1999/01528T patent/TR199901528T2/xx unknown
- 1997-11-26 IL IL12935297A patent/IL129352A0/xx unknown
- 1997-11-26 NZ NZ335159A patent/NZ335159A/xx unknown
- 1997-11-26 KR KR1019990703138A patent/KR20000049065A/ko not_active Application Discontinuation
- 1997-11-26 EP EP97949600A patent/EP0956017B1/en not_active Expired - Lifetime
- 1997-11-26 CZ CZ991252A patent/CZ125299A3/cs unknown
-
1999
- 1999-03-01 US US09/259,969 patent/US6077862A/en not_active Expired - Fee Related
- 1999-04-09 NO NO991700A patent/NO991700L/no not_active Application Discontinuation
-
2000
- 2000-09-29 US US09/676,031 patent/US6710065B1/en not_active Expired - Fee Related
- 2000-09-29 US US09/676,407 patent/US6482843B1/en not_active Expired - Fee Related
- 2000-09-29 US US09/676,029 patent/US6423735B1/en not_active Expired - Fee Related
- 2000-09-29 US US09/676,202 patent/US6420411B1/en not_active Expired - Fee Related
- 2000-09-29 US US09/676,032 patent/US6900235B1/en not_active Expired - Fee Related
- 2000-09-29 US US09/676,409 patent/US6423736B1/en not_active Expired - Fee Related
- 2000-09-29 US US09/676,030 patent/US6407131B1/en not_active Expired - Fee Related
- 2000-09-29 US US09/676,034 patent/US6864275B1/en not_active Expired - Fee Related
-
2003
- 2003-01-13 US US10/340,945 patent/US6984654B2/en not_active Expired - Fee Related
-
2004
- 2004-10-21 US US10/970,346 patent/US20050192328A1/en not_active Abandoned
-
2005
- 2005-08-26 US US11/212,300 patent/US20050288349A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1254282A (zh) | 治疗病毒感染和癌的苯并咪唑-2-氨基甲酸酯 | |
CN1244123A (zh) | 用于抑制癌生长的药盒,含有化疗剂和苯并咪唑并任选地含有增效剂 | |
CN1181014A (zh) | 抑制病毒和癌生长的含n-膦酰甘氨酸衍生物的药物组合物 | |
CN1181010A (zh) | 抑制肿瘤生长的含苯并咪唑衍生物的药物组合物 | |
US6265427B1 (en) | Pharmaceutical composition for the method of treating leukemia | |
CN1181701A (zh) | 抑制病毒和癌症生长的、含n-氯苯基甲氨酸化合物和n-氯苯基硫代甲氨酸化合物的药物组合物 | |
CN1195288A (zh) | 氟康唑抑制癌症生长的用途 | |
CN1192142A (zh) | 1h-1,2,4-三唑衍生物用于抑制癌症生长的用途 | |
JP2004509949A (ja) | 化合物および癌またはウイルス性感染症治療におけるその使用方法 | |
US20010041678A1 (en) | Compositions and methods for treating cancer | |
US20060009468A1 (en) | Method for treatment of cancer | |
AU763272B2 (en) | Benzimidazole-2-carbamates for the treatment of viral infections and cancer | |
EP3967310A1 (en) | Quinoline derivative used for soft tissue sarcoma combination therapy | |
JPH1081631A (ja) | 癌転移または再発抑制剤 | |
MXPA99006961A (en) | Kit for inhibiting the growth of cancers, comprising a chemotherapeutic agent and a benzimidazole, and optionally a potentiator |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |