CN113750242A - Nmn联合cd38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用 - Google Patents
Nmn联合cd38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用 Download PDFInfo
- Publication number
- CN113750242A CN113750242A CN202111259118.2A CN202111259118A CN113750242A CN 113750242 A CN113750242 A CN 113750242A CN 202111259118 A CN202111259118 A CN 202111259118A CN 113750242 A CN113750242 A CN 113750242A
- Authority
- CN
- China
- Prior art keywords
- nmn
- adriamycin
- nad
- inhibitor
- preventing
- 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
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 title claims abstract description 78
- 229940009456 adriamycin Drugs 0.000 title claims abstract description 21
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 title claims abstract description 16
- 206010048610 Cardiotoxicity Diseases 0.000 title claims abstract description 16
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 title claims abstract description 16
- 231100000259 cardiotoxicity Toxicity 0.000 title claims abstract description 16
- 239000003814 drug Substances 0.000 title claims abstract description 10
- 239000003112 inhibitor Substances 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 229940126634 CD38 inhibitor Drugs 0.000 claims abstract description 13
- VJQALSOBHVEJQM-UHFFFAOYSA-N COCCOC1CCC(CC1)Nc1cc(=O)n(C)c2ccc(cc12)-c1cncs1 Chemical compound COCCOC1CCC(CC1)Nc1cc(=O)n(C)c2ccc(cc12)-c1cncs1 VJQALSOBHVEJQM-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 9
- 229960004679 doxorubicin Drugs 0.000 claims description 18
- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 5
- 230000002107 myocardial effect Effects 0.000 claims description 3
- 230000000259 anti-tumor effect Effects 0.000 claims description 2
- 229940127089 cytotoxic agent Drugs 0.000 claims description 2
- 229940034982 antineoplastic agent Drugs 0.000 claims 2
- 230000000973 chemotherapeutic effect Effects 0.000 claims 1
- 230000004217 heart function Effects 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 5
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 4
- 239000002547 new drug Substances 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 238000012827 research and development Methods 0.000 abstract 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 36
- 229950006238 nadide Drugs 0.000 description 35
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 35
- DAYLJWODMCOQEW-TURQNECASA-O NMN(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(O)=O)O2)O)=C1 DAYLJWODMCOQEW-TURQNECASA-O 0.000 description 25
- 230000000694 effects Effects 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 210000005003 heart tissue Anatomy 0.000 description 6
- 230000009469 supplementation Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000019522 cellular metabolic process Effects 0.000 description 2
- 239000005515 coenzyme Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- BMKDZUISNHGIBY-ZETCQYMHSA-N (+)-dexrazoxane Chemical compound C([C@H](C)N1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-ZETCQYMHSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 108020005199 Dehydrogenases Proteins 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108030003379 NAD(+) synthases Proteins 0.000 description 1
- 102100033223 Nicotinamide phosphoribosyltransferase Human genes 0.000 description 1
- 108010064862 Nicotinamide phosphoribosyltransferase Proteins 0.000 description 1
- 108091093105 Nuclear DNA Proteins 0.000 description 1
- 239000012661 PARP inhibitor Substances 0.000 description 1
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 1
- 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 description 1
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 1
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 1
- 102000011990 Sirtuin Human genes 0.000 description 1
- 108050002485 Sirtuin Proteins 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004908 autophagic flux Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960000605 dexrazoxane Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 229940035756 doxorubicin injection Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000006676 mitochondrial damage Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 229940101270 nicotinamide adenine dinucleotide (nad) Drugs 0.000 description 1
- FAQDUNYVKQKNLD-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC2=C3[CH]C=CC=C3C(=O)N=N2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FAQDUNYVKQKNLD-UHFFFAOYSA-N 0.000 description 1
- 229960000572 olaparib Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明属于生物医药技术领域，公开了NMN联合CD38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用，其中NMN和CD38抑制剂的剂量比为0.1–100：1，通过NMN联合CD38抑制剂78c与抗肿瘤药物阿霉素联合使用时，NMN可以有效提高心脏NAD含量，显著减弱DIC，改善心功能，进而解除阿霉素临床应用的限制，为新药研发和创新疗法提供基础。
Description
技术领域
本发明属于生物医药技术领域，具体涉及NMN联合CD38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用。
背景技术
以阿霉素(Doxorubicin，DOX)为代表的蒽环类药物是一类重要的化疗药物，被广泛应用于实体和血液系统恶性肿瘤的治疗，如乳腺癌、急性白血病、淋巴瘤等。然而，阿霉素引起的心脏毒性(Doxorubicin-induced cardiotoxicity，DIC)严重限制了它的临床应用。尽管新型脂质体阿霉素提高了对肿瘤的靶向性，但是仍然没有彻底消除其引起的心脏毒性，阿霉素引起的充血性心力衰竭一旦发生，致死率高达50％。目前没有DIC有效治疗措施，右丙亚胺是现在FDA唯一批准的用于预防DIC的药物，但是其欠佳的效果和产生的副作用迫使人们不断寻找新型有效的防治药物。
阿霉素引起的心脏毒性机制主要包括线粒体损伤、细胞核DNA损伤、活性氧大量产生等。烟酰胺腺嘌呤二核苷酸(Nicotinamide adenine dinucleotide，NAD)是细胞代谢过程中的重要辅酶，参与线粒体电子转递体，是体内很多脱氢酶的辅酶，在维持线粒体稳态和细胞核损伤修复的过程中发挥重要作用。大量临床前研究表明，细胞内NAD水平的降低促进了衰老以及多种疾病的进展，例如神经退行性疾病、糖尿病、缺血性心脏病、心力衰竭等。通过外源补充NAD或者内源性激动NAD合成可以有效延缓衰老，防治多种疾病，最新研究还发现NAD稳态失衡促进了DIC发生，提高心脏NAD水平可以减少DIC。因此，NAD有望成为防治DIC以及其他疾病的重要靶点。
鉴于NAD的不稳定性，目前主要采用NAD前体物质烟酰胺单核苷酸(Nicotinamidemononucleotide，NMN)来补充NAD，尽管大量动物研究证实通过NMN提高组织NAD水平的可行性。但是，近期临床研究发现人体补充NMN并没有显著提高组织的NAD水平，NAD补充效率过低大大削弱了NAD在防治疾病中的作用，从而限制其广泛的临床应用。尤其在疾病状态下，NAD降低主要原因之一是受到CD38、PARP、Sirtuin等水解酶降解，其中CD38是降解NAD最主要的酶，研究表明NMN也可被CD38直接降解，阻碍其向NAD的转化。因此，在补充NAD的同时抑制NAD降解，将会极大提高NAD补充效率，提高NAD防治疾病的效率。
发明内容
发明人的前期研究发现阿霉素会引起全身血管内皮细胞高表达CD38，CD38严重消耗心脏等主要脏器组织的NAD，参与DIC发生，尽管外源补充NMN可以提高心脏组织NAD水平，但其对心功能的改善远未达到理想效果。基于此，本发明首次提出NMN联合CD38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用，通过提高心脏组织NAD摄取效率，从而减轻阿霉素引起的心脏毒性，为新药研发和创新疗法提供基础。
优选地，NMN和CD38抑制剂的剂量比为0.1–100：1。
另一方面，本发明还提出NMN联合CD38抑制剂在制备蒽环类抗肿瘤药物心肌保护剂中的用途。
优选地，所述蒽环类抗肿瘤药物为阿霉素。
再一方面，本发明还提出一种用于抗肿瘤的化疗药物，含有阿霉素和所述NMN联合CD38抑制剂。
与现有技术相比，本发明的有益效果在于：提高组织NAD水平被认为是防治多种疾病的重要手段，通过补充NAD有望实现防治DIC的效果，但是目前面临NAD补充效率低下的困难，无法充分发挥NAD治疗效果。本发明通过NMN联合CD38抑制剂78c与抗肿瘤药物阿霉素联合使用时，NMN可以有效提高心脏NAD含量，显著减弱DIC，改善心功能，进而解除阿霉素临床应用的限制，让更多肿瘤病人获益。
附图说明
通过阅读参照以下附图对非限制性实施例所作的详细描述，本发明的其它特征、目的和优点会变得更显著：
图1是实施例1中构建阿霉素心脏毒性动物模型的技术路线图。
图2是实施例1中阿霉素心脏毒性动物模型阿霉素处理后内皮细胞表达CD38情况，*p<0.05，**p<0.01，***p<0.001。
图3是实施例1中阿霉素心脏毒性动物模型心脏组织NAD含量情况，*p<0.05，**p<0.01，***p<0.001。
图4是实施例1中阿霉素心脏毒性动物模型的心功能情况，*p<0.05，**p<0.01，***p<0.001。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚，下面结合本发明实施例的附图，对本发明实施例的技术方案进行清楚、完整地描述。显然，所描述的实施例是本发明的一部分实施例，而不是全部的实施例。基于所描述的本发明的实施例，本领域普通技术人员在无需创造性劳动的前提下所获得的所有其它实施例，都属于本发明保护的范围。
以下实施例中涉及的小鼠购自常州卡文实验动物中心，NMN和78c药物购自Selleck Chemicals公司，阿霉素由美国Sigma公司提供，NAD检测试剂盒购自碧云天生物有限公司，动物实验已通过复旦大学附属中山医院伦理委员会批准。
DIC模型参见文献“Doxorubicin Blocks Cardiomyocyte Autophagic Flux byInhibiting Lysosome Acidification.Circulation.2016；133:1668–1687.”。
78c抑制CD38活性参考文献“A Potent and Specific CD38 InhibitorAmeliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+Decline.Cell Metabolism.2018.03.016”。
实施例1
按照如图1所示的技术路线构建阿霉素心脏毒性动物模型，具体为：对8周大的C57BL/6雄性小鼠尾静脉注射5mg/kg的阿霉素或者生理盐水，给药频率为每周一次，连续四周，阿霉素累积剂量为20mg/kg，DIC模型终点为最后一次给药4周后。药物联合应用：NMN用生理盐水溶解，78c用DMSO溶解。在阿霉素注射前3小时，给小鼠腹腔注射500mg/kg NMN以及10mg/kg CD38抑制剂78c，NMN用药频率为每两天一次，78c每天一次，一直持续到模型终点。模型结束后对小鼠进行超声心动图检测小鼠心脏功能，并取小鼠心肌组织，检测NAD含量，结果如图2–4所示。
如图2所示，阿霉素处理后，小鼠心脏组织CD38表达明显升高，并且主要表达在内皮细胞标志物CD31阳性的区域。如图3所示，小鼠接受阿霉素处理后，同时分组给予NAD合成酶Nampt激动剂P7C3、NAD消耗酶PARP抑制剂Olaparib、NAD消耗酶CD38抑制剂78c和NMN，与对照组相比，阿霉素处理后的小鼠心脏组织NAD含量明显下降，NMN或78c单独使用能够适量提高心脏NAD水平，但NMN与78c联合应用可以显著提高心脏组织NAD含量。如图4所示，模型终点对小鼠心功能进行评价，显示阿霉素处理显著降低了小鼠心脏射血分数(EF)和缩短分数(FS)，NMN或78c单独使用可以改善心功能，NMN联合78c可以显著改善心功能，效果明显。
基于上述动物实验可知，NMN联合CD38抑制剂是治疗阿霉素心脏毒性的新方法。对于临床上需要接受阿霉素化疗的病人可以给予NMN与CD38抑制剂78c预防DIC。
Claims (6)
1.NMN联合CD38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用。
2.根据权利要求1所述的应用，其特征在于，NMN和CD38抑制剂的剂量比为0.1–100：1。
3.NMN联合CD38抑制剂在制备蒽环类抗肿瘤药物心肌保护剂中的用途。
4.根据权利要求1所述的应用，其特征在于，所述蒽环类抗肿瘤药物为阿霉素。
5.一种用于抗肿瘤的化疗药物，含有阿霉素和所述NMN联合CD38抑制剂。
6.根据权利要求5所述的化疗药物，其特征在于，NMN和CD38抑制剂的剂量比为0.1–100：1。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111259118.2A CN113750242A (zh) | 2021-10-28 | 2021-10-28 | Nmn联合cd38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111259118.2A CN113750242A (zh) | 2021-10-28 | 2021-10-28 | Nmn联合cd38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113750242A true CN113750242A (zh) | 2021-12-07 |
Family
ID=78784556
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111259118.2A Pending CN113750242A (zh) | 2021-10-28 | 2021-10-28 | Nmn联合cd38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113750242A (zh) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103827293A (zh) * | 2011-06-29 | 2014-05-28 | 通用医疗公司 | 用于增强雌性生殖细胞中生物能状态的组合物和方法 |
| US20160279161A1 (en) * | 2013-11-14 | 2016-09-29 | Newsouth Innovation Pty Limited | Senescence and senescence associated secretory phenotype |
| CN108025187A (zh) * | 2015-04-28 | 2018-05-11 | 新南创新私人有限公司 | 靶向nad+以治疗化学疗法和放射疗法引发的认知损害、神经病变和不活动 |
| CN109475572A (zh) * | 2016-02-22 | 2019-03-15 | 宾夕法尼亚州大学信托人 | 用于增强肝再生的方法 |
| CN113143946A (zh) * | 2021-05-13 | 2021-07-23 | 清华大学 | 烟酰胺单核苷酸及其在抗肿瘤药物心肌损伤中的保护应用 |
| US20210267943A1 (en) * | 2018-06-25 | 2021-09-02 | Case Western Reserve University | Compositions and methods for treating tissue injury |
-
2021
- 2021-10-28 CN CN202111259118.2A patent/CN113750242A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103827293A (zh) * | 2011-06-29 | 2014-05-28 | 通用医疗公司 | 用于增强雌性生殖细胞中生物能状态的组合物和方法 |
| US20160279161A1 (en) * | 2013-11-14 | 2016-09-29 | Newsouth Innovation Pty Limited | Senescence and senescence associated secretory phenotype |
| CN108025187A (zh) * | 2015-04-28 | 2018-05-11 | 新南创新私人有限公司 | 靶向nad+以治疗化学疗法和放射疗法引发的认知损害、神经病变和不活动 |
| CN109475572A (zh) * | 2016-02-22 | 2019-03-15 | 宾夕法尼亚州大学信托人 | 用于增强肝再生的方法 |
| US20210267943A1 (en) * | 2018-06-25 | 2021-09-02 | Case Western Reserve University | Compositions and methods for treating tissue injury |
| CN113143946A (zh) * | 2021-05-13 | 2021-07-23 | 清华大学 | 烟酰胺单核苷酸及其在抗肿瘤药物心肌损伤中的保护应用 |
Non-Patent Citations (1)
| Title |
|---|
| MARIANA G. TARRAGO等: "A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline", 《CELL METABOLISM》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1778215B1 (en) | Anticancer effect enhancer | |
| WO2000076524A1 (en) | Combination cancer therapy comprising adenosine and deaminase enzyme inhibitor | |
| CN114306366B (zh) | 含nad和cd38抑制剂的药物组合物及其用途 | |
| KR102308387B1 (ko) | 고시폴, 펜포르민 및 항암제를 포함하는 암 예방 또는 치료용 약학적 조성물 | |
| CN109675041A (zh) | 用于治疗癌症的系统、方法和制剂 | |
| US20110250292A1 (en) | Composition for improving radiotherapy for cancer | |
| WO2019217164A1 (en) | Compositions and methods for treating cancer and other diseases | |
| WO2023092943A1 (zh) | 盐酸决奈达隆联合5-氟尿嘧啶在制备抗肿瘤药物中的应用 | |
| TWI547277B (zh) | Honokiol for the treatment or prevention of bladder cancer growth and metastasis and improve the cachexia new use | |
| US11141421B2 (en) | Antitumor agent for biliary tract cancer and method for treating biliary tract cancer | |
| CN110946856B (zh) | 一种防治蒽环类抗生素心脏毒性的药物组合物及其应用 | |
| EP1757283A1 (en) | Antitumor effect fortifier, antitumor agent and method of therapy for cancer | |
| CN113750242A (zh) | Nmn联合cd38抑制剂在制备预防或治疗阿霉素所致心脏毒性药物中的应用 | |
| CN108503676B (zh) | 用于癌症治疗的果糖类似物及其组合物 | |
| WO2019164010A1 (ja) | 膀胱がん用抗腫瘍剤および膀胱がんの処置方法 | |
| WO2009133963A1 (en) | Methods of administering antitumor agent comprising deoxycytidine derivative | |
| WO2019146129A1 (ja) | イソクエン酸デヒドロゲナーゼ変異を有する腫瘍に対する医薬組成物および抗腫瘍剤ならびにその利用 | |
| CN103550157A (zh) | 一种表阿霉素脂质体的制备及其抗肿瘤用途 | |
| CN114948951B (zh) | Fk506或其可药用衍生物和铁死亡诱导剂或其可药用衍生物联合在制备治疗癌症的药物中的用途 | |
| CN108324707A (zh) | 非诺贝特单药及联合化疗药在制备抗肿瘤药物中的应用 | |
| CN113633631B (zh) | 米铂脂质体在抗耐药性肿瘤的应用 | |
| KR102212699B1 (ko) | 유방암 예방 또는 치료용 조성물 | |
| Guo et al. | 177Lu-FA-DOTA-PEG-PLGA Nanoparticles Show Antitumor Efficiency in Targeting Ovarian Cancer | |
| CN116870020A (zh) | 一种抗肿瘤的药物组合物及其应用 | |
| CN116829000A (zh) | 组合疗法 |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20211207 |
|
| RJ01 | Rejection of invention patent application after publication |