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WO2016062271A1 - 抗生素药物用于制备治疗癌症的医药组合物的用途 - Google Patents

抗生素药物用于制备治疗癌症的医药组合物的用途 Download PDF

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WO2016062271A1
WO2016062271A1 PCT/CN2015/092686 CN2015092686W WO2016062271A1 WO 2016062271 A1 WO2016062271 A1 WO 2016062271A1 CN 2015092686 W CN2015092686 W CN 2015092686W WO 2016062271 A1 WO2016062271 A1 WO 2016062271A1
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antibiotic
hcl
hydrochloride
cancer
sodium
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陈丘泓
庄秀美
萧乃文
梁瑞岳
陈筱彤
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Launx Biomedical Co Ltd
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  • Tetracycline antibiotics a generic term for a broad-spectrum antibiotic family of drugs, is named for its hydrogenation of tetraphenyl nucleus.
  • the drug has a broad spectrum of antibacterial activity, and has a strong effect on Gram-negative bacteria, Gram-positive bacteria, spirochetes, chlamydia, rickettsia, mycoplasma, actinomycetes and amoeba.
  • the original culture solution in the 96-well plate was aspirated, and 100 ul of the commercially available drug was added to each well at a concentration of 10 uM. After 72 hours, 100 ul of diluted WST-1 reagent was added to each well, and the dilution ratio was broth and WST. The volume ratio of -1 stock solution is 9:1. Finally, the total volume of each well plate is 200ul. Then, the 96-well plate is placed at 37 ° C for 30-90 minutes. The elisa reader (ELISA) is used for OD450 detection. The absorbance was measured and the survival rate of each cancer cell line was calculated.
  • ELISA elisa reader

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Abstract

抗生素在制备抑制多种癌症的医药组合物中的应用，所述抗生素选自胺基配糖体抗生素，抗霉菌剂抗生素，头孢子菌类抗生素，β-丙酰胺抗生素类，氯霉素抗生素，红霉素类抗生素，青霉素类抗生素，四环素类抗生素及其他抗生素中的一种或多种。

Description

抗生素药物用于制备治疗癌症的医药组合物的用途 技术领域
本发明为多种抗生素药物的新适应症的应用，尤其该多种药物为通过临床实验且具有抑制多种癌症的用途。
背景技术
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。癌症的治疗可区分为手术治疗、放射线治疗、化学治疗及标靶治疗。
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。在临床治疗选择上，通常会结合一到数种化疗药物以及标靶治疗，希望能藉由不同机制来杀死癌细胞以提高治疗效果，但事实上，还是常遇到患者对于治疗药物的反应不佳。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。
抗生素(antibiotic)由微生物(包括细菌、真菌、放线菌属)所产生的具有抑制其它类微生物生长、生存的一类次级代谢产物，以及用化学方法合成或半合成的类似化合物。在定义上是一较广的概念，包括抗细菌抗生素、抗真菌抗生素以及对付其他微小病原的抗生素；但临床实务中，抗生素常常是指抗细菌抗生素。
发明人依据长年的研究经验，人类的癌症细胞常常有与正常细胞具有不同的表现性状，型态上的差异或是作用机转的变化或许也有可能被视为一种外来的 侵入者，而每一种癌症细胞所在的位置不同，变异的状态又与所处的环境有关，因此，第一个提出使用抗生素药物抑制癌症细胞的发明概念并且进行实验。
相对的，在这些已经使用数十年抗生素，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数据，因此，若应用在癌症方面，这项新发展会更省时、减少成本，也能和其他治疗方式结合来提高效果。
在发明人提出美国临时申请案之后，亦有其他的教授深入研究探讨其可能性，近期亦陆续有相关的研究提出并证实发明人的发明内容，该教授根据内共生理论(Endosymbiotic Theory)提出相类似的假设，意即粒线体曾经是细菌，后来被大型细菌并吞后，在其细胞内与之共生，因此粒线体和一般细胞结构不太一样，它有自己的基因，和原核生物(如细菌)比较接近。这种差异就也许就能被设计成像标靶治疗一样，单独抑制癌症细胞的治疗。
尽管如此，药物开发依然是重要的医学议题，必须经过繁复的临床前试验才能进入临床试验，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。此外，除了药物本身是否能大量制造的难题外，还需克服药物安全性、病人筛选、试用剂量等问题，即便药物已经通过FDA的核准并上市，亦有可能因上市后于人体发现不良反应而强制下架回收，由此可见药物开发具有一定的困难程度。
发明内容
为解决上述的问题，本发明针对通过临床实验的多种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抗生素药物对正常细胞没有或仅有微小的毒性，但至于抗生素在正常细胞与肿瘤细胞之间是否具有选择性的影响，还有待更多的研究厘清，而且并非所有的抗生素在相同的条件下均能有效的抑制肿瘤细胞， 需要有许多的问题进行克服。
名词定义
抗生素依据药物的结构可以分为九大类，包含胺基(氨基)配糖体抗生素(又称为氨基糖苷类抗生素)、抗霉菌剂抗生素、头孢子菌类抗生素、β-丙酰胺抗生素类、氯霉素抗生素、青霉素类抗生素、红霉素类抗生素、四环素类抗生素，与其他类抗生素。
1.氨基糖苷类抗生素，氨基糖苷类抗生素是具有氨基糖与氨基环醇结构的一类抗生素，在临床主要用于对革兰氏阴性菌、绿脓杆菌等感染的治疗。本发明中的抗生素药物包含在本类别的有Amikacin sulfate、Amikacin hydrate、Netilmicin Sulfate；
2.抗霉菌剂抗生素，是一系列抗霉菌的抗生素。本发明中的抗生素药物包含在本类别的有Posaconazole、Artemisinin、Fluconazole、Ketoconazole、Voriconazole、Natamycin(Pimaricin)、Clotrimazole(Canesten)、Amphotericin B(Abelcet)、Flucytosine(Ancobon)、Amorolfine Hydrochloride、Terbinafine(Lamisil,Terbinex)、Butoconazole nitrate、Chloroxine、Bifonazole、Tioconazole、Nystatin(Mycostatin)、Miconazole nitrate、Liranaftate、Isoconazole nitrate(Travogen)、Terbinafine hydrochloride(Lamisil)、Ciclopirox ethanolamine、Caspofungin acetate、Naftifine HCl、Sertaconazole nitrate、Pyrithione zinc、Sulconazole Nitrate、Climbazole、Valnemulin HCl；
3.头孢子菌类抗生素，头孢菌素，又名先锋霉素，是一系列属于β-内酰胺类的抗生素。与头孢霉素一并细分为头孢烯。本发明中的抗生素药物包含在本类别的有Cefdinir(Omnicef)、Cefoperazone(Cefobid)、Cefditoren pivoxil、Cephalexin(Cefalexin)、Cefoselis sulfate、Ceftiofur hydrochloride、Cefaclor (Ceclor)、Ceftazidime Pentahydrate、Moxalactam Disodium、Cephapirin Sodium；
4.β-丙酰胺抗生素类(Beta-lactam antibiotic)是一种种类很广的抗生素，其特征是，包括青霉素及其衍生物、头孢菌素、单酰胺环类、碳青霉烯和青霉烯类酶抑制剂等。基本上所有在其分子结构中包括β-内酰胺核的抗生素均属于β内酰胺类抗生素。它是现有的抗生素中使用最广泛的一类。本发明中的抗生素药物包含在本类别的有Doripenem Hydrate、Meropenem、Aztreonam、Sulbactam、Sulbactam sodium(Unasyn)、Biapenem；
5.氯霉素抗生素，氯霉素有着很广泛的活跃性，能有效对抗革兰氏阳性菌，包括大部份的抗药性金黄色葡萄球菌、革兰氏阴性菌及厌氧性生物。本发明中的抗生素药物包含在本类别的有Gatifloxacin、Daptomycin、Sulfapyridine(Dagenan)、Sulfameter(Bayrena)、Chloramphenicol(Chloromycetin)；
6.青霉素类抗生素，青霉素(Penicillin，或音译盘尼西林)是指分子中含有青霉烷、能破坏细菌的细胞壁并在细菌细胞的繁殖期起杀菌作用的一类抗生素，是由青霉菌中提炼出的抗生素。青霉素属于β-内酰胺类抗生素(β－lactams),β-内酰胺类抗生素包括青霉素、头孢菌素、碳青霉烯类、单环类、头霉素类等。本发明中的抗生素药物包含在本类别的有Amoxicillin sodium(Amox)、Ampicillin sodium、Carbenicillin disodium、Dicloxacillin Sodium、Ampicillin Trihydrate、Benzylpenicillin sodium、Mezlocillin Sodium、Piperacillin Sodium；
7.红霉素类抗生素，红霉素(Erythromycin)是一种大环内酯类的抗生素。抗菌范围与青霉素相似；主要用于对青霉素已经产生耐药性的葡萄球菌、链球菌、腹泻等胃肠道反应。本发明中的抗生素药物包含在本类别的有Teicoplanin、Linezolid(Zyvox)、Erythromycin(E-Mycin)、Erythromycin Ethylsuccinate、Spiramycin、Tilmicosin、Azithromycin Dihydrate、Dirithromycin、Fidaxomicin；
8.四环素类抗生素，一个广效抗生素(Broad-spectrum antibiotic)药物家族的泛称，因其氢化并四苯母核而得名。本类药物抗菌谱广，对革兰氏阴性菌、革兰氏阳性菌、螺旋体、衣原体、立克次氏体、支原体、放线菌和阿米巴原虫都有较强的作用。本发明中的抗生素药物包含在本类别的有Marbofloxacin、Moxifloxacin hydrochloride、Oxytetracycline(Terramycin)、Tigecycline、Oxytetracycline dihydrate、Tetracycline HCl、Chlortetracycline HCl、Minocycline HCl、Rolitetracycline；
本发明提供一种抗生素药物用于制备治疗癌症的医药组合物的用途，所述医药组合物(药物)是由有效剂量的抗生素及药学上可接受的盐类所组成。
本发明提供一种抗病毒药物用于制备治疗癌症的医药组合物的用途，所述医药组合物是由有效剂量的抗病毒药物及药学上可接受的盐类所组成。
本发明所述的抗生素是选自胺基配糖体抗生素、抗霉菌剂抗生素、头孢子菌类抗生素、β－丙酰胺抗生素类、氯霉素抗生素、红霉素类抗生素、青霉素类抗生素、四环素类抗生素及其他抗生素中的一种或多种。
本发明一实施例中，所述胺基配糖体抗生素是选自由Amikacin sulfate、Amikacin hydrate、Netilmicin Sulfate中的一种或多种所组成的药物。
本发明一实施例中，所述抗霉菌剂抗生素是选自由Posaconazole、Artemisinin、Fluconazole、Ketoconazole、Voriconazole、Natamycin(Pimaricin)、Clotrimazole(Canesten)、Amphotericin B(Abelcet)、Flucytosine(Ancobon)、Amorolfine Hydrochloride、Terbinafine(Lamisil,Terbinex)、Butoconazole nitrate、Chloroxine、Bifonazole、Tioconazole、Nystatin(Mycostatin)、Miconazole nitrate、Liranaftate、Isoconazole nitrate(Travogen)、Terbinafine hydrochloride(Lamisil)、Ciclopirox ethanolamine、Caspofungin acetate、Naftifine HCl、Sertaconazole nitrate、 Pyrithione zinc、Sulconazole Nitrate、Climbazole、Valnemulin HCl中的一种或多种所组成的药物。
本发明一实施例中，所述头孢子菌类抗生素是选自由Cefdinir(Omnicef)、Cefoperazone(Cefobid)、Cefditoren pivoxil、Cephalexin(Cefalexin)、Cefoselissulfate、Ceftiofur hydrochloride、Cefaclor(Ceclor)、Ceftazidime Pentahydrate、Moxalactam Disodium、Cephapirin Sodium中的一种或多种所组成的药物。
本发明一实施例中，所述β-丙酰胺抗生素是选自由Doripenem Hydrate、Meropenem、Aztreonam、Sulbactam、Sulbactam sodium(Unasyn)、Biapenem中的一种或多种所组成的药物。
本发明一实施例中，所述氯霉素抗生素是选自由Gatifloxacin、Daptomycin、Sulfapyridine(Dagenan)、Sulfameter(Bayrena)、Chloramphenicol(Chloromycetin)中的一种或多种所组成的药物。
本发明一实施例中，所述青霉素类抗生素是选自由Amoxicillin sodium(Amox)、Ampicillin sodium、Carbenicillin disodium、Dicloxacillin Sodium、Ampicillin Trihydrate、Benzylpenicillin sodium、Mezlocillin Sodium、PiperacillinSodium中的一种或多种所组成的药物。
本发明一实施例中，所述红霉素类抗生素是选自由Teicoplanin、Linezolid(Zyvox)、Erythromycin(E-Mycin)、Erythromycin Ethylsuccinate、Spiramycin、Tilmicosin、Azithromycin Dihydrate、Dirithromycin、Fidaxomicin中的一种或多种所组成的药物。
本发明一实施例中，所述四环素类抗生素是选自由Marbofloxacin、Moxifloxacin hydrochloride、Oxytetracycline(Terramycin)、Tigecycline、Oxytetracycline dihydrate、Tetracycline HCl、Chlortetracycline HCl、Minocycline HCl、Rolitetracycline中的一种或多种所组成的药物。
本发明一实施例中，所述其他抗生素是选自由Norfloxacin(Norxacin)、Enoxacin(Penetrex)、Pefloxacin mesylate、Sparfloxacin、Levofloxacin(Levaquin)、Sarafloxacin HCl、Nalidixic acid(NegGram)、Lomefloxacin hydrochloride(Maxaquin)、Enrofloxacin、Clinafloxacin(PD127391)、Orbifloxacin、ClinafoxacinHCl、Piromidic Acid、Cinoxacin、Difloxacin HC、Rifabutin(Mycobutin)、Rifapentine(Priftin)、Pyrazinamide(Pyrazinoic acid amide)、Rifampin(Rifadin,Rimactane)、Ethionamide、Rifaximin(Xifaxan)、Protionamide(Prothionamide)、Isoniazid(Tubizid)、D-Cycloserine、Streptomycin sulfate、Clofazimine、Nitrofurazone、Sulfanilamide、Sulfadiazine、Metronidazole(Flagyl)、Sulfamethoxazole、Sulfisoxazole、Sulfamethizole(Proklar)、Sulfadimethoxine、Clindamycin phosphate、Fenbendazole(Panacur)、Sulfadoxine(Sulphadoxine)、Secnidazole(Flagentyl)、Clindamycin palmitate HCl、Clindamycin、Sulfathiazole、Trimethoprim、Sulfamerazine、Pentamidine、Colistin Sulfate(polypeptide)、toltrazuril、tinidazoleMequinol、Bacitracin、Cetylpyridinium Chloride、Sulfaguanidine、Paromomycin Sulfate、Domiphen Bromide、Chlorquinaldol、Furaltadone HCl、Primaquine Diphosphate、Carbadox、Colistimethate Sodium、Meclocycline Sulfosalicylate、Thiostrepton、Bekanamycin、Clofoctol、Ritonavir、Entecavir hydrate、Artemisinin、Megestrol Acetate、Lansoprazole、Lopinavir(ABT-378)、Ondansetron hydrochloride、Resveratrol、Stavudine、TenofovirDisoproxil Fumarate、Tenofovir(Viread)、Cidofovir(Vistide)、Telaprevir(VX-950)、Saxagliptin(BMS-477118,Onglyza)、Darunavir Ethanolate(Prezista)、Docosanol(Abreva)、Amprenavir(Agenerase)、Telbivudine(Sebivo,Tyzeka)、 Hydrocortisone(Cortisol)、Didanosine(Videx)、Emtricitabine(Emtriva)、Lamivudine(Epivir)、Adefovir Dipivoxil(Preveon,Hepsera)、Zalcitabine、Prednisolone(Hydroretrocortine)、Nevirapine(Viramune)、Trifluridine(Viroptic)、Vidarabine(Vira-A)、Acyclovir(Aciclovir)、Albendazole Oxide(Ricobendazole)、Chenodeoxycholic acid、Valaciclovir HCl、Ganciclovir、Idoxuridine、Crystal violet、Rimantadine(Flumadine)、Taurine(organic acid)、Diclazuril(anticoccidial drug)、Rebamipide、Orphenadrine citrate(Norflex)、Terazosin HCl(Hytrin)、Lafutidine、Dextrose、BIBR-1048(Dabigatran)、Rosuvastatin calcium(Crestor)、Ammonium Glycyrrhizinate(AMGZ)、Amfebutamone(Bupropion)、Clonidine hydrochloride(Catapres)、Fluocinolone acetonide(Flucort-N)、Loperamide hydrochloride、Mycophenolic(Mycophenolate)、Olanzapine(Zyprexa)、Racecadotril(Acetorphan)、Rosiglitazone maleate、Salbutamol sulfate(Albuterol)、Tenoxicam(Mobiflex)、Vardenafil(Vivanza)、Dopamine hydrochloride(Inotropin)、Ritodrine hydrochloride(Yutopar)、Riboflavin(Vitamin B2)、Clomipramine hydrochloride(Anafranil)、Tiotropium Bromide hydrate、Isoprenaline hydrochloride、Medroxyprogesterone acetate、Xylometazoline HCl、Phenacetin、Trazodone hydrochloride(Desyrel)、Brompheniramine、Acemetacin(Emflex)、Dabrafenib(GSK2118436)、Paroxetine HCl、Zanamivir(Relenza)、Niflumic acid、Medetomidine HCl、Diclofenac Potassium、Ulipristal、Indacaterol Maleate、Biotin (Vitamin B7)、Sodium salicylate、Methylthiouracil、Darifenacin HBr、Benztropine mesylate、Abacavir sulfate、Antipyrine、Amitriptyline HCl、Azatadine dimaleate、Triflusal、Pemirolast(BMY 26517)potassium、Homatropine Bromide、Carbimazole、 Spironolactone、Ropivacaine HCl、Escitalopram oxalate、Bismuth Subcitrate Potassium(mineral)、Chlorpropamide、Nifuroxazide、Penciclovir、Salicylanilide、Betamipron、Ethacridine lactate monohydrate(aromatic compound)、Aminothiazole、Florfenicol、Cetrimonium Bromide(antiseptic)、Thonzonium Bromide(detergent)、Pasiniazid中的一种或多种所组成的药物。
本发明一实施例中，所述癌症为肺癌、肠道癌、大肠直肠癌、前列腺癌、膀胱癌、子宫颈癌、乳癌及血癌中的一种或多种。
本发明一实施例中，所述药物的有效剂量浓度为20mg/kg/天～500mg/kg/天。
现今癌症药物费用动辄上万至数百万元，若未来更进一步证实抗生素对肿瘤的疗效，对于无法负担昂贵治疗的患者们，这些便宜而历史悠久的药物，会是带来健康的新希望。
附图说明
图1为本发明抗生素用药应用于抑制癌细胞的分析结果
实施方式
建立细胞株
参照表一，将不同癌症类型的细胞株进行继代培养，计算细胞数目后，将2×106细胞数置入培养皿，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、细胞株及其培养所用的培养液
Figure PCTCN2015092686-appb-000001
Figure PCTCN2015092686-appb-000002
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。
抗生素用药应用于抑制癌细胞分析结果
依据细胞存活分析方法针对取得的九大类抗生素药物，包含胺基配糖体抗生素、抗霉菌剂抗生素、头孢子菌类抗生素、β-丙酰胺抗生素类、氯霉素抗生素、青霉素类抗生素、红霉素类抗生素、四环素类抗生素，以及抗病毒类药物进行测试抑制癌细胞生长的效果。
实验结果明显的显示有许多的抗生素并无法有效的抑制癌症的细胞的生长(表二)。
表二、对癌症细胞株无抑制效果的抗生素
抗生素 抑制癌症细胞株效果
Artemisinin(青蒿素) 0
Cefoselis sulfate 0
Doripenem Hydrate 0
Marbofloxacin 0
Moxifloxacin hydrochloride 0
Norfloxacin(Norxacin) 0
Flucytosine(Ancobon) 0
Amorolfine Hydrochloride 0
Chloramphenicol(Chloromycetin) 0
Hydrocortisone(Cortisol) 0
Terbinafine(Lamisil,Terbinex) 0
ValaciclovirHCl 0
Ganciclovir 0
Sulfamethizole(Proklar) 0
Sulbactam 0
Sulphadimethoxine 0
Rimantadine(Flumadine) 0
Racecadotril(Acetorphan) 0
Rosiglitazone maleate 0
Salbutamol sulfate(Albuterol) 0
Sulfadoxine(Sulphadoxine) 0
Tenoxicam(Mobiflex) 0
Ritodrine hydrochloride(Yutopar) 0
Brompheniramine 0
Acemetacin(Emflex) 0
Amikacin hydrate 0
Trimethoprim 0
Biotin(Vitamin B7) 0
Sulfamerazine 0
Sodium salicylate 0
Methylthiouracil 0
Benztropine mesylate 0
Triflusal 0
Carbimazole 0
Netilmicin Sulfate 0
Ropivacaine HCl 0
Erythromycin Ethylsuccinate 0
Escitalopram oxalate 0
tinidazole 0
Bismuth Subcitrate Potassium 0
Sulfaguanidine 0
Mezlocillin Sodium 0
Penciclovir 0
Salicylanilide 0
Florfenicol 0
Dirithromycin 0
Piromidic Acid 0
而相对的各种的抗生素药物分子对于各种癌症细胞的抑制效果也不尽相同(图一)，经过发明人实验结果，证实抗生素药物Ritonavir(利托那韦)、Entecavir hydrate(恩替卡韦水合物)、Posaconazole(泊沙康唑)、Artemisinin(青蒿素)、Megestrol Acetate(醋酸甲地孕酮、去氢甲孕酮)、Fluconazole、Gatifloxacin、Ketoconazole、Lansoprazole、Acitretin、Biapenem、Cefoselis sulfate、Daptomycin、Doripenem Hydrate、Lopinavir(ABT-378)、Meropenem、Ondansetron hydrochloride(Zofran)、Resveratrol、Stavudine、Teicoplanin、Tenofovir Disoproxil Fumarate、Tenofovir(Viread)、Tigecycline、Linezolid(Zyvox)、Voriconazole、Marbofloxacin、Moxifloxacin hydrochloride、Cefaclor(Ceclor)、Cephalexin(Cefalexin)、Aztreonam(Azactam,Cayston)、Norfloxacin(Norxacin)、Cidofovir(Vistide)、Natamycin(Pimaricin)、Telaprevir(VX-950)、Saxagliptin(BMS-477118,Onglyza)、Cefdinir(Omnicef)、Clotrimazole(Canesten)、Cefoperazone(Cefobid)、Sulfapyridine(Dagenan)、Sulfameter(Bayrena)、Darunavir Ethanolate(Prezista)、Erythromycin(E-Mycin)、Amphotericin B(Abelcet)、Docosanol(Abreva)、Amprenavir(Agenerase)、Nitrofurazone(Nitrofural)、Telbivudine(Sebivo,Tyzeka)、Flucytosine(Ancobon)、Amorolfine Hydrochloride、Chloramphenicol(Chloromycetin)、Sulfanilamide、Hydrocortisone(Cortisol)、Didanosine(Videx)、Emtricitabine(Emtriva)、Lamivudine(Epivir)、Adefovir Dipivoxil(Preveon,Hepsera)、Zalcitabine、Terbinafine(Lamisil,Terbinex)、Prednisolone(Hydroretrocortine)、Rifabutin(Mycobutin)、Nevirapine(Viramune)、Enoxacin(Penetrex)、Rifapentine(Priftin)、Pyrazinamide(Pyrazinoic  acid amide)、Rifampin(Rifadin,Rimactane)、Cefditoren pivoxil、Sulfadiazine、Oxytetracycline(Terramycin)、Ethionamide、Trifluridine(Viroptic)、Vidarabine(Vira-A)、Rifaximin(Xifaxan)、Acyclovir(Aciclovir)、Butoconazole nitrate、Albendazole Oxide(Ricobendazole)、Chloroxine、Chenodeoxycholic acid、Bifonazole、Pefloxacin mesylate、Valaciclovir HCl、Ganciclovir、Protionamide(Prothionamide)、Idoxuridine、Sparfloxacin、Metronidazole(Flagyl)、Tioconazole、Sulfamethoxazole、Sulfisoxazole、Crystal violet、Nystatin(Mycostatin)、Isoniazid(Tubizid)、Levofloxacin(Levaquin)、Miconazole nitrate、Sulfamethizole(Proklar)、Sulbactam、Sulphadimethoxine、Rimantadine(Flumadine)、Sarafloxacin HCl、Liranaftate、D-Cycloserine、Taurine、Diclazuril、Rebamipide、Clindamycin phosphate、Oxytetracycline dihydrate、Orphenadrine citrate(Norflex)、Terazosin HCl(Hytrin)、Lafutidine、Dextrose(D-glucose)、BIBR-1048(Dabigatran)、Rosuvastatin calcium(Crestor)、Nalidixic acid(NegGram)、Ammonium Glycyrrhizinate(AMGZ)、Amfebutamone(Bupropion)、Clonidine hydrochloride(Catapres)、Fenbendazole(Panacur)、Fluocinolone acetonide(Flucort-N)、Loperamide hydrochloride、Mycophenolic(Mycophenolate)、Olanzapine(Zyprexa)、Racecadotril(Acetorphan)、Rosiglitazone maleate、Salbutamol sulfate(Albuterol)、Sulfadoxine(Sulphadoxine)、Tenoxicam(Mobiflex)、Vardenafil(Vivanza)、Dopamine hydrochloride(Inotropin)、Ritodrine hydrochloride(Yutopar)、Isoconazole nitrate(Travogen)、Secnidazole(Flagentyl)、Lomefloxacin hydrochloride(Maxaquin)、Riboflavin(Vitamin B2)、Clomipramine hydrochloride(Anafranil)、Ceftiofur hydrochloride、Tiotropium Bromide hydrate、Sulbactam sodium(Unasyn)、Terbinafine hydrochloride(Lamisil)、Amoxicillin sodium (Amox)、Isoprenaline hydrochloride、Medroxyprogesterone acetate、Streptomycin sulfate、Tetracycline HCl、Xylometazoline HCl、Phenacetin、Trazodone hydrochloride(Desyrel)、Brompheniramine、Clindamycin palmitate HCl、Acemetacin(Emflex)、Dabrafenib(GSK2118436)、Clindamycin、Paroxetine HCl、Zanamivir(Relenza)、Niflumic acid、Ciclopirox ethanolamine、Enrofloxacin、Medetomidine HCl、Diclofenac Potassium、Amikacin sulfate、Caspofungin acetate、Ulipristal、Indacaterol Maleate、Sulfathiazole、Amikacin hydrate、Trimethoprim、Biotin(Vitamin B7)、Sulfamerazine、Sodium salicylate、Methylthiouracil、Darifenacin HBr、Naftifine HCl、Sertaconazole nitrate、Benztropine mesylate、Abacavir sulfate、Ampicillin sodium、Antipyrine、Carbenicillin disodium、Amitriptyline HCl、Azatadine dimaleate、Triflusal、Clinafloxacin(PD127391)、Pentamidine、Pemirolast(BMY 26517)potassium、Homatropine Bromide、Colistin Sulfate、toltrazuril、Carbimazole、Netilmicin Sulfate、Spironolactone、Ropivacaine HCl、Erythromycin Ethylsuccinate、Escitalopram oxalate、tinidazole、Pyrithione zinc、Mequinol、Spiramycin、Bismuth Subcitrate Potassium、Clofazimine、Dicloxacillin Sodium、Sulconazole Nitrate、Tilmicosin、Bacitracin、Azithromycin Dihydrate、Ampicillin Trihydrate、Orbifloxacin、Chlortetracycline HCl、Benzylpenicillin sodium、Chlorpropamide、Cetylpyridinium Chloride、Sulfaguanidine、Climbazole、Mezlocillin Sodium、Nifuroxazide、Paromomycin Sulfate、Penciclovir、Domiphen Bromide、Salicylanilide、Betamipron、Chlorquinaldol、Ethacridine lactate monohydrate、Aminothiazole、Florfenicol、Furaltadone HCl、Dirithromycin、Valnemulin HCl、Piperacillin Sodium、Minocycline HCl、Fidaxomicin、Primaquine Diphosphate、Cetrimonium Bromide、Carbadox、Ceftazidime Pentahydrate、Clinafoxacin HCl、 Colistimethate Sodium、Meclocycline Sulfosalicylate、Moxalactam Disodium、Piromidic Acid、Rolitetracycline、Thiostrepton、Thonzonium Bromide、Cinoxacin、Bekanamycin、Difloxacin HCl、Cephapirin Sodium、Clofoctol、Pasiniazid等药物对于不同的癌症细胞有明显的抑制效果(如表三)。
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。
Figure PCTCN2015092686-appb-000003
Figure PCTCN2015092686-appb-000004
Figure PCTCN2015092686-appb-000005
Figure PCTCN2015092686-appb-000006
Figure PCTCN2015092686-appb-000007
Figure PCTCN2015092686-appb-000008
Figure PCTCN2015092686-appb-000010
Figure PCTCN2015092686-appb-000011
Figure PCTCN2015092686-appb-000012
Figure PCTCN2015092686-appb-000013
Figure PCTCN2015092686-appb-000014
Figure PCTCN2015092686-appb-000015
Figure PCTCN2015092686-appb-000016
Figure PCTCN2015092686-appb-000017
Figure PCTCN2015092686-appb-000018
Figure PCTCN2015092686-appb-000019
Figure PCTCN2015092686-appb-000020

Claims (12)

  1. 一种抗生素药物用于制备治疗癌症的医药组合物的用途，其特征是，所述医药组合物是由有效剂量的抗生素及药学上可接受的盐类所组成。
  2. 如权利要求1所述的用途，其特征是，所述抗生素是选自胺基配糖体抗生素、抗霉菌剂抗生素、头孢子菌类抗生素、β-丙酰胺抗生素类、氯霉素抗生素、红霉素类抗生素、青霉素类抗生素、四环素类抗生素及其他抗生素中的一种或多种。
  3. 如权利要求2所述的用途，其特征是，所述胺基配糖体抗生素是选自由Amikacin sulfate、Amikacin hydrate、Netilmicin Sulfate中的一种或多种所组成的药物。
  4. 如权利要求2所述的用途，其特征是，所述抗霉菌剂抗生素是选自由Posaconazole、Artemisinin、Fluconazole、Ketoconazole、Voriconazole、Natamycin(Pimaricin)、Clotrimazole(Canesten)、Amphotericin B(Abelcet)、Flucytosine(Ancobon)、Amorolfine Hydrochloride、Terbinafine(Lamisil,Terbinex)、Butoconazole nitrate、Chloroxine、Bifonazole、Tioconazole、Nystatin(Mycostatin)、Miconazole nitrate、Liranaftate、Isoconazole nitrate(Travogen)、Terbinafine hydrochloride(Lamisil)、Ciclopirox ethanolamine、Caspofungin acetate、Naftifine HCl、Sertaconazole nitrate、Pyrithione zinc、Sulconazole Nitrate、Climbazole、Valnemulin HCl中的一种或多种所组成的药物。
  5. 如权利要求2所述的用途，其特征是，所述头孢子菌类抗生素是选自由Cefdinir(Omnicef)、Cefoperazone(Cefobid)、Cefditoren pivoxil、Cephalexin(Cefalexin)、Cefoselis sulfate、Ceftiofur hydrochloride、Cefaclor(Ceclor)、Ceftazidime  Pentahydrate、Moxalactam Disodium、Cephapirin Sodium中的一种或多种所组成的药物。
  6. 如权利要求2所述的用途，其特征是，所述β-丙酰胺抗生素是选自由Doripenem Hydrate、Meropenem、Aztreonam、Sulbactam、Sulbactam sodium(Unasyn)、Biapenem中的一种或多种所组成的药物。
  7. 如权利要求2所述的用途，其特征是，所述氯霉素抗生素是选自由Gatifloxacin、Daptomycin、Sulfapyridine(Dagenan)、Sulfameter(Bayrena)、Chloramphenicol(Chloromycetin)所中的一种或多种组成之药物。
  8. 如权利要求2所述的用途，其特征是，所述青霉素类抗生素是选自由Amoxicillin sodium(Amox)、Ampicillin sodium、Carbenicillin disodium、Dicloxacillin Sodium、Ampicillin Trihydrate、Benzylpenicillin sodium、Mezlocillin Sodium、Piperacillin Sodium中的一种或多种所组成的药物。
  9. 如权利要求2所述的用途，其特征是，所述红霉素类抗生素是选自由Teicoplanin、Linezolid(Zyvox)、Erythromycin(E-Mycin)、Erythromycin Ethylsuccinate、Spiramycin、Tilmicosin、Azithromycin Dihydrate、Dirithromycin、Fidaxomicin中的一种或多种所组成的药物。
  10. 如权利要求2所述的用途，其特征是，所述四环素类抗生素是选自由Marbofloxacin、Moxifloxacin hydrochloride、Oxytetracycline(Terramycin)、Tigecycline、Oxytetracycline dihydrate、Tetracycline HCl、Chlortetracycline HCl、Minocycline HCl、Rolitetracycline中的一种或多种所组成的药物。
  11. 如权利要求2所述的用途，其特征是，所述其他抗生素是选自由Norfloxacin(Norxacin)、Enoxacin(Penetrex)、Pefloxacin mesylate、Sparfloxacin、Levofloxacin(Levaquin)、Sarafloxacin HCl、Nalidixic acid(NegGram)、Lomefloxacin  hydrochloride(Maxaquin)、Enrofloxacin、Clinafloxacin(PD127391)、Orbifloxacin、Clinafoxacin HCl、Piromidic Acid、Cinoxacin、Difloxacin HC、Rifabutin(Mycobutin)、Rifapentine(Priftin)、Pyrazinamide(Pyrazinoic acid amide)、Rifampin(Rifadin, Rimactane)、Ethionamide、Rifaximin(Xifaxan)、Protionamide(Prothionamide)、Isoniazid(Tubizid)、D-Cycloserine、Streptomycin sulfate、Clofazimine、Nitrofurazone、Sulfanilamide、Sulfadiazine、Metronidazole(Flagyl)、Sulfamethoxazole、Sulfisoxazole、Sulfamethizole(Proklar)、Sulfadimethoxine、Clindamycin phosphate、Fenbendazole(Panacur)、Sulfadoxine(Sulphadoxine)、Secnidazole(Flagentyl)、Clindamycin palmitate HCl、Clindamycin、Sulfathiazole、Trimethoprim、Sulfamerazine、Pentamidine、Colistin Sulfate(polypeptide)、toltrazuril、tinidazoleMequinol、Bacitracin、Cetylpyridinium Chloride、Sulfaguanidine、Paromomycin Sulfate、Domiphen Bromide、Chlorquinaldol、Furaltadone HCl、Primaquine Diphosphate、Carbadox、Colistimethate Sodium、Meclocycline Sulfosalicylate、Thiostrepton、Bekanamycin、Clofoctol、Ritonavir、Entecavir hydrate、Artemisinin、Megestrol Acetate、Lansoprazole、Lopinavir(ABT-378)、Ondansetron hydrochloride、Resveratrol、Stavudine、Tenofovir Disoproxil Fumarate、Tenofovir(Viread)、Cidofovir (Vistide)、Telaprevir(VX-950)、Saxagliptin(BMS-477118,Onglyza)、Darunavir Ethanolate(Prezista)、Docosanol(Abreva)、Amprenavir(Agenerase)、Telbivudine(Sebivo,Tyzeka)、Hydrocortisone(Cortisol)、Didanosine(Videx)、Emtricitabine(Emtriva)、Lamivudine(Epivir)、Adefovir Dipivoxil(Preveon,Hepsera)、Zalcitabine、Prednisolone(Hydroretrocortine)、Nevirapine(Viramune)、Trifluridine(Viroptic)、Vidarabine(Vira-A)、Acyclovir(Aciclovir)、Albendazole Oxide (Ricobendazole)、Chenodeoxycholic acid、Valaciclovir HCl、Ganciclovir、Idoxuridine、Crystal violet、Rimantadine(Flumadine)、Taurine(organic acid)、Diclazuril(anticoccidial drug)、Rebamipide、Orphenadrine citrate(Norflex)、Terazosin HCl(Hytrin)、Lafutidine、Dextrose、BIBR-1048(Dabigatran)、Rosuvastatin calcium(Crestor)、Ammonium Glycyrrhizinate(AMGZ)、Amfebutamone(Bupropion)、Clonidine hydrochloride(Catapres)、Fluocinolone acetonide(Flucort-N)、Loperamide hydrochloride、Mycophenolic(Mycophenolate)、Olanzapine(Zyprexa)、Racecadotril(Acetorphan)、Rosiglitazone maleate、Salbutamol sulfate(Albuterol)、Tenoxicam(Mobiflex)、Vardenafil(Vivanza)、Dopamine hydrochloride(Inotropin)、Ritodrine hydrochloride(Yutopar)、Riboflavin(Vitamin B2)、Clomipramine hydrochloride(Anafranil)、Tiotropium Bromide hydrate、Isoprenaline hydrochloride、Medroxyprogesterone acetate、Xylometazoline HCl、Phenacetin、Trazodone hydrochloride(Desyrel)、Brompheniramine、Acemetacin(Emflex)、Dabrafenib(GSK2118436)、Paroxetine HCl、Zanamivir(Relenza)、Niflumic acid、Medetomidine HCl、Diclofenac Potassium、Ulipristal、Indacaterol Maleate、Biotin(Vitamin B7)、Sodium salicylate、Methylthiouracil、Darifenacin HBr、Benztropine mesylate、Abacavir sulfate、Antipyrine、Amitriptyline HCl、Azatadine dimaleate、Triflusal、Pemirolast(BMY 26517)potassium、Homatropine Bromide、Carbimazole、Spironolactone、Ropivacaine HCl、Escitalopram oxalate、Bismuth Subcitrate Potassium(mineral)、Chlorpropamide、Nifuroxazide、Penciclovir、Salicylanilide、Betamipron、Ethacridine lactate monohydrate(aromatic compound)、Aminothiazole、Florfenicol、Cetrimonium Bromide(antiseptic)、Thonzonium Bromide(detergent)、 Pasiniazid中的一种或多种所组成的药物。
  12. 如权利要求1所述的用途，其特征是，所述癌症为肺癌、肠道癌、大肠直肠癌、前列腺癌、膀胱癌、子宫颈癌、乳癌及血癌中的一种或多种。
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