CN108484633A - 一种增强砷剂治疗白血病的单体化合物 - Google Patents
一种增强砷剂治疗白血病的单体化合物 Download PDFInfo
- Publication number
- CN108484633A CN108484633A CN201810485376.4A CN201810485376A CN108484633A CN 108484633 A CN108484633 A CN 108484633A CN 201810485376 A CN201810485376 A CN 201810485376A CN 108484633 A CN108484633 A CN 108484633A
- Authority
- CN
- China
- Prior art keywords
- leukaemia
- art
- apoptosis
- arsenic
- artesunate
- 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
- 208000032839 leukemia Diseases 0.000 title claims abstract description 17
- 150000001875 compounds Chemical class 0.000 title claims abstract description 9
- 229910052785 arsenic Inorganic materials 0.000 title claims abstract description 8
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 title claims abstract description 8
- 230000002708 enhancing effect Effects 0.000 title claims abstract description 8
- 210000004027 cell Anatomy 0.000 claims abstract description 23
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 claims abstract description 20
- FIHJKUPKCHIPAT-AHIGJZGOSA-N artesunate Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@@H](OC(=O)CCC(O)=O)[C@@H]4C FIHJKUPKCHIPAT-AHIGJZGOSA-N 0.000 claims abstract description 20
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229960004991 artesunate Drugs 0.000 claims abstract description 16
- 230000006907 apoptotic process Effects 0.000 claims abstract description 13
- 230000000694 effects Effects 0.000 claims abstract description 9
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 claims abstract description 8
- 230000004663 cell proliferation Effects 0.000 claims abstract description 7
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 6
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 5
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 5
- 230000000259 anti-tumor effect Effects 0.000 claims abstract description 4
- 230000007246 mechanism Effects 0.000 claims abstract description 4
- 206010059866 Drug resistance Diseases 0.000 claims abstract description 3
- 206010064390 Tumour invasion Diseases 0.000 claims abstract description 3
- 210000004204 blood vessel Anatomy 0.000 claims abstract description 3
- 230000009400 cancer invasion Effects 0.000 claims abstract description 3
- 230000024245 cell differentiation Effects 0.000 claims abstract description 3
- 230000006698 induction Effects 0.000 claims abstract description 3
- 230000001105 regulatory effect Effects 0.000 claims abstract description 3
- 230000035945 sensitivity Effects 0.000 claims abstract description 3
- 230000019491 signal transduction Effects 0.000 claims abstract description 3
- 229960000981 artemether Drugs 0.000 claims abstract 2
- 229930101531 artemisinin Natural products 0.000 claims abstract 2
- 229960002521 artenimol Drugs 0.000 claims abstract 2
- BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 claims abstract 2
- SXYIRMFQILZOAM-HVNFFKDJSA-N dihydroartemisinin methyl ether Chemical compound C1C[C@H]2[C@H](C)CC[C@H]3[C@@H](C)[C@@H](OC)O[C@H]4[C@]32OO[C@@]1(C)O4 SXYIRMFQILZOAM-HVNFFKDJSA-N 0.000 claims abstract 2
- 229930183339 qinghaosu Natural products 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 7
- 231100000673 dose–response relationship Toxicity 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 229940044683 chemotherapy drug Drugs 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- 241001465754 Metazoa Species 0.000 abstract description 3
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 abstract description 2
- 230000000118 anti-neoplastic effect Effects 0.000 abstract description 2
- 238000002512 chemotherapy Methods 0.000 abstract description 2
- 238000000338 in vitro Methods 0.000 abstract description 2
- 229930002330 retinoic acid Natural products 0.000 abstract description 2
- 230000014509 gene expression Effects 0.000 description 11
- 238000010172 mouse model Methods 0.000 description 8
- 230000003833 cell viability Effects 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 3
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 3
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 3
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 description 2
- 230000035519 G0 Phase Effects 0.000 description 2
- 230000010190 G1 phase Effects 0.000 description 2
- 108010002687 Survivin Proteins 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002574 poison Substances 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 101100372758 Danio rerio vegfaa gene Proteins 0.000 description 1
- 230000004668 G2/M phase Effects 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 101150030763 Vegfa gene Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 208000022532 enlargement of lymph nodes Diseases 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 231100000925 very toxic Toxicity 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/20—Spiro-condensed systems
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/203—Retinoic acids ; Salts thereof
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/36—Arsenic; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
本发明涉及一种增强砷剂治疗白血病的单体化合物,包括:青蒿素、双氢青蒿素、青蒿琥酯、蒿甲醚以及其他青蒿素类衍生物,其中青蒿素类衍生物本身有抗白血病的作用,可以增强三氧化二砷治疗白血病的疗效,青蒿素类衍生物、砷剂和维甲酸三者联用抗白血病效果最好,可以通过抑制肿瘤细胞增殖和诱导肿瘤细胞分化和凋亡、调控细胞信号转导、抑制肿瘤血管新生、抑制肿瘤侵袭转移、增敏抗肿瘤化疗药物及逆转耐药等多种机制发挥抗肿瘤作用,以实现通过体内动物实验和体外细胞实验证实青蒿素类衍生物联合砷剂对治疗白血病有确切疗效。
Description
技术领域
本发明属于中药技术领域,具体涉及一种增强砷剂治疗白血病的单体化合物。
背景技术
白血病(leukemia)是一类造血干细胞恶性克隆性疾病。克隆性白血病细胞因为增殖失控、分化障碍、凋亡受阻等机制在骨髓和其他造血组织中大量增殖累积,并浸润其他非造血组织和器官,同时抑制正常造血功能。临床可见不同程度的贫血、出血、感染发热以及肝、脾、淋巴结肿大和骨骼疼痛。目前白血病的病因尚未完全阐明。较为公认的因素有:病毒因素、化学因素、放射因素以及遗传因素。按起病的缓急可分为急、慢性白血病。儿童及青少年急性白血病多起病急骤。起病缓慢者以老年及部分青年病人居多,病情逐渐进展。研究表明,我国各地区白血病的发病率在各种肿瘤中占主导地位。
三氧化二砷是毒药“砒霜”的主要成分,其辛、大热,有大毒;归肺、肝经。外用攻毒杀虫,蚀疮去腐;内服劫痰平喘,截疟。是熟知的中药毒性药。中医药近几年来使用最多而且疗效最好的是用三氧化二砷治疗白血病。研究显示,其作用机制主要有降解融合蛋白、活化半胱氨酸激酶家族、影响Bcl-2蛋白家族、开放线粒体膜通透性转运孔、调节谷胱甘肽氧化还原系统等。但是三氧化二砷临床应用剂量和安全剂量相近,在应用过程中易出现一些不良反应,从而限制了其在临床上的应用。
青蒿琥酯(Artesunate,ART)是青蒿素衍生物之一,除了抗疟疾作用,其抗肿瘤作用更是引起人们的广泛关注,临床应用前途广泛。近年来,国内外学者研究发现,ART可通过抑制肿瘤细胞增殖和诱导肿瘤细胞分化和凋亡、调控细胞信号转导、抑制肿瘤血管新生、抑制肿瘤侵袭转移、增敏抗肿瘤化疗药物及逆转耐药等多种机制发挥抗肿瘤作用。研究表明,应用ART作用NB4细胞,流式结果显示ART作用NB4细胞24h后即可引起细胞凋亡,且呈给药时间剂量依赖性,证实了ART能诱导NB4细胞凋亡。
发明内容
发明目的:本发明的目的在于提供一种增强砷剂治疗白血病的单体化合物
本发明提供的一种增强三氧化二砷治疗白血病的单体化合物可以制成任何临床上可以接受的剂型。
附图说明
附图1为ART与ATO及RA联用对模型小鼠生存时间的影响;
附图2为ART与ATO及RA联用对模型小鼠外周血GFP的影响;
图2-1为空白对照组;
图2-2为模型组;
图2-3为ATO组;
图2-4为ATO+RA组;
图2-5为ATO+ART组;
图2-6为ART+RA组;
图2-7为ATO+RA+ART组;
附图3为ART与ATO及RA联用对模型小鼠骨髓细胞CD34+/CD117+的影响;
图3-1为空白对照组;
图3-2为模型组;
图3-3为ATO组;
图3-4为ATO+RA组;
图3-5为ATO+ART组;
图3-6为ART+RA组;
图3-7为ATO+RA+ART组;
附图4为ART与ATO及RA联用对模型小鼠脏器损伤的影响;
图4-1为空白对照组;
图4-2为模型组;
图4-3为ATO组;
图4-4为ATO+RA组;
图4-5为ATO+ART组;
图4-6为ART+RA组;
图4-7为ATO+RA+ART组;
附图5为ART与ATO及RA联用NB4细胞相关蛋白的影响;
图5-1为NF-κB蛋白表达;
图5-2为Survivin蛋白表达;
图5-3为MMP-9蛋白表达;
图5-4为VEGF蛋白表达;
图5-5为β-actin蛋白表达。
具体实施例
具体实施例1
建立动物模型考察青蒿琥酯增强三氧化二砷联合为甲酸治疗APL的疗效
结果:ART 100mg/kg与ATO 2mg/kg及RA 7mg/kg联用干预APL模型小鼠后,能显著延长模型动物生存时间;ATO+RA、RA+ART、ATO+RA+ART组小鼠外周血GFP显著降低(P<0.05);ATO+RA、RA+ART、ATO+RA+ART组CD34+/CD117+阳性表达的细胞比例明显下降(P<0.05);可以显著改善模型动物的病理损伤程度。实验结果见表1、表2、表3、图1、图2、图3、图4。
表1.ART与ATO及RA联用对模型小鼠生存时间的影响(n=6)
#:与对照组比较P<0.05
表2.ART与ATO及RA联用对模型小鼠外周血GFP的表达的影响(n=6)
#:与模型组比较P<0.05
表3.ART与ATO及RA联用对模型小鼠骨髓细胞CD34+/CD117+的表达的影响(n=6)
#:与模型组比较P<0.05
具体实施例2
体外实验考察ART与三氧化二砷及维甲酸联用对NB4细胞相关蛋白的影响
结果:ART 0.4μM与ATO 1μM及RA 1μM联用干预NB4细胞后,与空白对照组比较,各给药组的NF-κB蛋白出现了下调表达,其中单用RA组下调较少,其余各组下调明显。
Survivin蛋白的表达结果显示,三药联用有效抑制了该蛋白的表达,但其余各给药组均无较大作用。MMP-9蛋白表达结果显示,ATO+ART、ART+RA、ATO+RA+ART四个给药组对MMP-9蛋白的表达起到了显著的抑制作用。见图5.
具体实施例3
MTT法测定As203对NB4细胞的细胞活力的影响
结果:As203剂量依赖性减弱细胞活力。As203对NB4细胞的半数抑制浓度IC50=2.00μM。实验结果见表4。
表4.MTT法测定As203对NB4细胞的细胞活力的影响(n=6)
##:与对照组比较P≤0.01
具体实施例4
MTT法测定青蒿琥酯对NB4细胞的细胞活力的影响
结果:与空白对照组比较,青蒿琥酯0.25、0.50、1.00、2.00、4.00μM组均可显著性的抑制NB4细胞增殖(P<0.01),且呈浓度依赖性,其半数抑制浓度为0.80μM,实验结果见表5。
表5.MTT法测定青蒿琥酯对NB4细胞的细胞活力的影响(n=6)
##:与对照组比较P≤0.01
具体实施例5
MTT法测定青蒿琥酯联合As203对NB4细胞的细胞活力的影响
结果:与空白对照组比较,0.4μM青蒿琥酯组细胞增值抑制率明显升高(P<0.05);1.0μM三氧化二砷组与空白对照组比较可使细胞增殖抑制率显著性升高(P<0.01)。三氧化二砷联合青蒿琥酯组较空白对照组可使细胞增殖抑制率极显著升高(P<0.01),见表6。
表6.MTT法测定青蒿琥酯联合As203对NB4细胞的细胞活力的影响(n=6)
##:与对照组比较P≤0.01;#:与对照组比较P<0.05
具体实施例6
三氧化二砷联合青蒿琥酯对NB4细胞周期的影响
结果:与空白对照组比较,1μM三氧化二砷组细胞G0/G1期细胞比例明显增加(P<0.01),S期细胞比例明显减少。0.4μM青蒿琥酯组NB4细胞周期较空白对照组无明显变化。0.4μM青蒿琥酯联合1μM三氧化二砷组细胞G0/G1期细胞比例明显增加,G2/M期细胞比例减少,见表7。
表7.三氧化二砷联合青蒿琥酯对NB4细胞周期的影响(n=3,)
##:与对照组比较P≤0.01
具体实施例7
三氧化二砷联合青蒿琥酯对NB4细胞凋亡的影响
结果:与空白对照组比较,0.4μM青蒿琥酯组NB4细胞凋亡率明显升高(P<0.05);
1μM三氧化二砷组NB4细胞凋亡率较空白对照组明极显著升高(P<0.01)。青蒿琥酯0.4μM联合三氧化二砷1μM组细胞凋亡率较空白对照组极显著升高(P<0.01),见表8。
表8.三氧化二砷联合青蒿琥酯对NB4细胞凋亡的影响(n=3,)
##:与对照组比较P≤0.01;#:与对照组比较P<0.05。
Claims (3)
1.一种增强砷剂治疗白血病的单体化合物,其特征在于:包括:青蒿素、双氢青蒿素、青蒿琥酯、蒿甲醚以及其他青蒿素类衍生物。
2.根据权利要求1所述的方法,其特征在于:青蒿琥酯可通过抑制肿瘤细胞增殖和诱导肿瘤细胞分化和凋亡、调控细胞信号转导、抑制肿瘤血管新生、抑制肿瘤侵袭转移、增敏抗肿瘤化疗药物及逆转耐药等多种机制发挥抗肿瘤作用,以实现ART作用NB4细胞24h后即可引起细胞凋亡,且呈给药时间剂量依赖性,以实现ART能诱导NB4细胞凋亡。
3.根据权利要求1所述的方法,其特征在于:可以制成任何临床上可以接受的剂型,包括化合物与三氧化二砷以外的砷剂两者联用,还包括化合物与三氧化二砷以外的其他砷剂的多种联用方法在治疗白血病方面的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810485376.4A CN108484633A (zh) | 2018-05-21 | 2018-05-21 | 一种增强砷剂治疗白血病的单体化合物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810485376.4A CN108484633A (zh) | 2018-05-21 | 2018-05-21 | 一种增强砷剂治疗白血病的单体化合物 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN108484633A true CN108484633A (zh) | 2018-09-04 |
Family
ID=63353023
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810485376.4A Pending CN108484633A (zh) | 2018-05-21 | 2018-05-21 | 一种增强砷剂治疗白血病的单体化合物 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108484633A (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110693903A (zh) * | 2019-11-28 | 2020-01-17 | 中国中医科学院中药研究所 | 一种治疗急性单核细胞白血病的药物及三氧化二砷和双氢青蒿素的应用 |
CN114129561A (zh) * | 2020-09-04 | 2022-03-04 | 澳门大学 | 青蒿素类药物在制备防治肿瘤切除术后复发及转移的药物中的应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102247340A (zh) * | 2010-05-20 | 2011-11-23 | 上海亚盛医药科技有限公司 | 阿朴棉子酚酮在制备用于肿瘤治疗的药物中的应用 |
CN107050014A (zh) * | 2017-05-26 | 2017-08-18 | 遵义医学院附属医院 | 青蒿琥酯作为抗白血病肿瘤药的应用 |
-
2018
- 2018-05-21 CN CN201810485376.4A patent/CN108484633A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102247340A (zh) * | 2010-05-20 | 2011-11-23 | 上海亚盛医药科技有限公司 | 阿朴棉子酚酮在制备用于肿瘤治疗的药物中的应用 |
CN107050014A (zh) * | 2017-05-26 | 2017-08-18 | 遵义医学院附属医院 | 青蒿琥酯作为抗白血病肿瘤药的应用 |
Non-Patent Citations (4)
Title |
---|
YING LI ET AL.: "Artesunate possesses anti-leukemia properties that can be enhanced by arsenic trioxide", 《LEUKEMIA & LYMPHOMA》 * |
吴蕾等: "青蒿琥酯诱导NB4细胞凋亡机制的研究", 《中国药房》 * |
岳庆喜等: "三氧化二砷和青蒿素抗肿瘤的机制研究进展", 《药学学报》 * |
杨森: "青蒿素增强三氧化二砷的抗肿瘤作用并降低其心脏毒性的研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110693903A (zh) * | 2019-11-28 | 2020-01-17 | 中国中医科学院中药研究所 | 一种治疗急性单核细胞白血病的药物及三氧化二砷和双氢青蒿素的应用 |
CN114129561A (zh) * | 2020-09-04 | 2022-03-04 | 澳门大学 | 青蒿素类药物在制备防治肿瘤切除术后复发及转移的药物中的应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR101512495B1 (ko) | 혈구 감소 관련 질환 예방 및 치료용 약물을 제조하기 위한 악티게닌의 용도 | |
WO2016107579A1 (zh) | 黄酮醇作为脑靶向增效剂的制备和应用 | |
CN102552908B (zh) | 含青蒿素及青蒿素类衍生物和Bcl-2抑制剂的药物组合物及其应用 | |
CN108484633A (zh) | 一种增强砷剂治疗白血病的单体化合物 | |
US11903923B2 (en) | Use of andrographolide derivatives in preparation of medicaments for preventing and treating inflammatory bowel diseases | |
CN103179967A (zh) | 抗肿瘤药物组合物 | |
CN107050014A (zh) | 青蒿琥酯作为抗白血病肿瘤药的应用 | |
CN105126030B (zh) | 一种辅助抗肺癌的壮药组合物 | |
TWI646964B (zh) | 用於降低癌症治療藥物副作用之醫藥組合物、製備方法及其用途 | |
KR20160141748A (ko) | 항암제 및 부작용 경감제 | |
Thomas et al. | Arsenic: a beneficial therapeutic poison-a historical overview | |
CN101879174A (zh) | 连翘酯苷a在制备治疗流感药物中的用途 | |
CN102805799A (zh) | 一种具有抗恶性肿瘤功效的中药组合物 | |
CN106309758A (zh) | 一种抗胃肠癌的药物组合物 | |
CN113908149A (zh) | 刺芒柄花素在制备防治急性肺损伤药物中的用途 | |
CN102961451A (zh) | 一种用于冠心病心绞痛的中药组合物 | |
CN112618569A (zh) | 一种用于治疗尿路上皮癌的药物 | |
CN110063989A (zh) | 一种治疗食管癌的药物组合物及其制备方法 | |
Patel et al. | The Use of Nutraceuticals in the Top Five Cancers with the Highest Number of Deaths Globally | |
CN104688748A (zh) | 一种含有熊果酸和环磷酰胺的药物组合物 | |
CN102232957A (zh) | 3-乙酰氧基-8,24-羊毛甾二烯-21-酸的抗肿瘤活性及其在医药中的应用 | |
CN108992463A (zh) | 一种治疗肺癌的组合物及药物制剂 | |
CN105982888B (zh) | 一种含青蒿素和紫杉醇的联合用药物及其用途 | |
CN111249298B (zh) | 一种含有马杜霉素和顺铂的抗癌药物组合物 | |
CN103405542B (zh) | 一种治疗化疗后白细胞减少的中药 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180904 |
|
WD01 | Invention patent application deemed withdrawn after publication |