CN113209058A - 去甲二氢愈创木酸在制备mcr-1酶抑制剂中的应用 - Google Patents
去甲二氢愈创木酸在制备mcr-1酶抑制剂中的应用 Download PDFInfo
- Publication number
- CN113209058A CN113209058A CN202110524966.5A CN202110524966A CN113209058A CN 113209058 A CN113209058 A CN 113209058A CN 202110524966 A CN202110524966 A CN 202110524966A CN 113209058 A CN113209058 A CN 113209058A
- Authority
- CN
- China
- Prior art keywords
- mcr
- nordihydroguaiaretic acid
- polymyxin
- preparation
- enzyme inhibitor
- 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.)
- Granted
Links
- HCZKYJDFEPMADG-TXEJJXNPSA-N masoprocol Chemical compound C([C@H](C)[C@H](C)CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-TXEJJXNPSA-N 0.000 title claims abstract description 80
- HCZKYJDFEPMADG-UHFFFAOYSA-N erythro-nordihydroguaiaretic acid Natural products C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 0.000 title claims abstract description 39
- 229960003951 masoprocol Drugs 0.000 title claims abstract description 39
- 101150004219 MCR1 gene Proteins 0.000 title claims abstract description 36
- 239000002532 enzyme inhibitor Substances 0.000 title claims abstract description 9
- 229940125532 enzyme inhibitor Drugs 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 241000588724 Escherichia coli Species 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 10
- 241000607142 Salmonella Species 0.000 claims abstract description 8
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 6
- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Polymers CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 claims description 14
- YKQOSKADJPQZHB-YNWHQGOSSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1s)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Polymers CCC(C)CCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O YKQOSKADJPQZHB-YNWHQGOSSA-N 0.000 claims description 14
- 108010078777 Colistin Proteins 0.000 claims description 12
- XDJYMJULXQKGMM-UHFFFAOYSA-N polymyxin E1 Natural products CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O XDJYMJULXQKGMM-UHFFFAOYSA-N 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 108010040201 Polymyxins Proteins 0.000 abstract description 18
- 241000894006 Bacteria Species 0.000 abstract description 11
- 208000015181 infectious disease Diseases 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 8
- 241000588747 Klebsiella pneumoniae Species 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 6
- 239000003242 anti bacterial agent Substances 0.000 abstract description 5
- 229940088710 antibiotic agent Drugs 0.000 abstract description 5
- 230000009885 systemic effect Effects 0.000 abstract description 5
- 238000004659 sterilization and disinfection Methods 0.000 abstract description 3
- 241000588921 Enterobacteriaceae Species 0.000 abstract description 2
- 230000035945 sensitivity Effects 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 7
- 241000588914 Enterobacter Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 2
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000012224 working solution Substances 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 108010068385 carbapenemase Proteins 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- 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
- A61P31/04—Antibacterial agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及去甲二氢愈创木酸在制备MCR‑1酶抑制剂中的应用，通过棋盘法和时间‑杀菌曲线法验证去甲二氢愈创木酸能够恢复多粘菌素对MCR‑1大肠杆菌、肺炎克雷氏菌和沙门氏菌等革兰氏阴性肠杆菌的杀菌活性，通过建立小鼠全身感染模型证明去甲二氢愈创木酸联用多粘菌素对能够产生MCR‑1阳性菌造成的感染具有良好的治疗效果。因此去甲二氢愈创木可以与抗生素联用，增加对超级耐药菌使用药物的选择性，降低多黏菌素用量，恢复多粘菌素对革兰氏阴性菌的敏感性有着重要意义。
Description
技术领域
本发明公开了一种天然化合物去甲二氢愈创木酸的新用途，进一步讲，涉及去甲二氢愈创木酸在制备MCR-1酶抑制剂中的医用用途，属于医学制药技术领域。
背景技术
细菌耐药性的问题对全球公共卫生安全造成了很大的危害，严重影响了人体健康及养殖业的发展。特别是以产碳青霉烯酶的革兰氏阴性菌引起的感染所导致的病情较为严重，多重耐药菌的出现以及对革兰氏阴性菌有活性的新抗菌药物的缺乏，使临床上以碳青霉烯类抗生素治疗的失败率和死亡率显著升高。多粘菌素是抗生素治疗耐药菌的“最后一道防线”。然而随着MCR-1的发现，抗生素治疗的“最后一道防线”被冲破，耐多粘菌素和耐碳青霉烯类抗生素的肠杆菌将面临无药可用的情况。目前尚无有效的MCR-1抑制剂的报道，因此，开发新的安全有效的药物具有十分重要的意义。
去甲二氢愈创木酸是一种从常青灌木中提取的天然产物，常被作为食品添加剂使用。具有抗氧化，抗菌抗病毒，抗风湿，增强机体免疫力，降血糖等多种医学功效，曾被广泛的用作医药和化妆品原料。目前大量研究表明去甲二氢愈创木酸能够抑制乳腺癌、肝癌、肺癌、大肠癌及胶质瘤等多种肿瘤的发生。但截至目前国内外未见去甲二氢愈创木酸在制备MCR-1抑制剂中的相关报道。
发明内容
本发明提供了一种去甲二氢愈创木酸在制备MCR-1酶抑制剂中的医用用途，公开了去甲二氢愈创木酸能够抑制MCR-1酶的活性，恢复多粘菌素对MCR-1大肠杆菌和沙门氏菌等革兰氏阴性肠杆菌的杀菌活性,并有效的降低了抗生素的耐用性。
本发明所述的去甲二氢愈创木酸，其分子式：C18H22O4，分子量：302.26；
本发明通过棋盘法最小抑菌浓度试验和时间-杀菌曲线法验证了去甲二氢愈创木酸能够抑制MCR-1酶的活性并恢复多粘菌素对MCR-1阳性肠杆菌的抗菌活性，并通过抗生素连续传代培养验证了去甲二氢愈创木酸能够降低抗生素的耐用性。试验所用肠杆菌主要包括MCR-1阳性大肠杆菌、肺炎克雷伯菌和沙门氏菌。进一步通过大肠杆菌建立小鼠全身感染模型证明去甲二氢愈创木酸联用多粘菌素对能够产生MCR-1的肠杆菌造成的感染具有良好的治疗效果。
本发明的积极效果在于：
提供了去甲二氢愈创木酸在制备MCR-1酶抑制剂中的新医用用途，公开了去甲二氢愈创木酸能够抑制MCR-1酶的活性，恢复多粘菌素对MCR-1肠杆菌的杀菌活性。体内实验中，去甲二氢愈创木酸联用多粘菌素对表达MCR-1的细菌性感染，尤其是MCR-1阳性肠杆菌引起的感染具有良好的治疗效果，具有广泛的医用用途。
附图说明
图1-3为本发明去甲二氢愈创木酸联合多粘菌素E对MCR-1阳性大肠杆菌、沙门氏菌和肺炎克雷伯菌的时间-杀菌曲线；
图4为本发明去甲二氢愈创木酸联合多粘菌素E对MCR-1阳性大肠杆菌的连续传代期间的时间-MIC倍数变化曲线；
图5为本发明去甲二氢愈创木酸联合多粘菌素E对大肠杆菌小鼠全身感染肝脏的菌落定植。
具体实施方式
通过以下实施例进一步举例描述本发明，并不以任何方式限制本发明，在不背离本发明的技术解决方案的前提下，对本发明所作的本领域普通技术人员容易实现的任何改动或改变都将落入本发明的权利要求范围之内。
试验例1
最小抑菌浓度试验
将不同浓度的抗生素工作液和去甲二氢愈创木酸工作液分别加入已灭菌的96孔培养基中，按棋盘法进行倍比稀释，确定去甲二氢愈创木酸、多粘菌素单用及二者联用的MIC值，计算部分抑菌浓度指数(FIC)。FIC＝MIC(多粘菌素联合)/MIC(多粘菌素单用)+MIC(去甲二氢愈创木酸联合)/MIC(去甲二氢愈创木酸单用)，结果见表1：
表1去甲二氢愈创木酸联用多粘菌素对MCR-1阳性大肠杆菌、肺炎克雷伯菌和沙门氏菌的MIC及FIC值
结论：去甲二氢愈创木酸单独应用不具备抑菌效果，与多粘菌素联用能够降低多粘菌素对MCR-1阳性大肠杆菌的MIC值8倍，对MCR-1阳性沙门氏菌MIC值8倍，对MCR-1阳性肺炎克雷伯菌MIC值32倍FIC数值表明二者具有协同作用。
试验例2
时间-杀菌曲线试验
将来自平板的单个细菌菌落接种到LB培养基过夜培养，以达到约108CFU/ml的浓度。接下来，将对数生长期的细菌加入到无抗生素对照组、多粘菌素E组、去甲二氢愈创木酸组、多粘菌素E组及去甲二氢愈创木酸联用，细菌终浓度为5×107CFUs/ml在孵育后0、1、3、5、7、9小时的时间点，取出100μl每个样品进行菌落计数。绘制时间-杀菌曲线(图1-3)。
结论：去甲二氢愈创木酸联用多粘菌素E能够在1h内均能彻底杀死MCR-1阳性大肠杆菌、肺炎克雷伯菌、沙门氏菌。
试验例3
细菌耐药性实验
将细菌在2μg/ml多粘菌素E和2μg/ml多粘菌素E及32μg/ml联合组使用的LB中连续传代培养。将没有任何药物传代的细菌最为对照。每天确定每组的最小抑菌浓度，并记录最小抑菌浓度倍数的变化。重复该过程16天。该测定一式三份进行。以检查获得性耐药性(图4)。
试验例4
小鼠全身感染菌落定植试验
我们选取具有代表性的大肠杆菌建立了小鼠全身感染模型
BALB/C小鼠(雌性，约20g)保定后，经腹腔注射MCR-1阳性大肠杆菌悬液(1.6×106CFUs)，建立小鼠全身感染模型。
菌落定植试验
小鼠腹腔注射MCR-1阳性大肠杆菌后，立即分别皮下注射5mg/kg(50μl)的溶解于灭菌水的多粘菌素E、100mg/kg(50μl)的去甲二氢愈创木酸DMSO溶液，及多粘菌素E(5mg/kg)联用去甲二氢愈创木酸(100mg/kg)，每8h给药一次，一共给药三次。阳性对照组给与50μl的DMSO空白溶剂，不给予任何药物进行治疗；另单独设立未感染小鼠的溶剂对照组，皮下给予50μl的DMSO空白溶剂以考察所用DMSO溶剂的安全性。按给药方案给药后，给药36h后处死小鼠，取小鼠肝脏称重，匀浆，倍比稀释后涂板计数，结果见附图5。
结论：经去甲二氢愈创木酸联用多粘菌素E治疗后，显著降低小鼠肝脏的菌落定植数，去甲二氢愈创木酸或多粘菌素E单独治疗组不具有显著的效果。
Claims (3)
1.去甲二氢愈创木酸在制备MCR-1酶抑制剂中应用。
2.如权利要求1所述的去甲二氢愈创木酸在制备MCR-1酶抑制剂中应用，其特征在于去甲二氢愈创木酸与多粘菌素E联用后能够恢复多粘菌素E对MCR-1阳性大肠杆菌和MCR-1阳性沙门氏菌的杀菌活性。
3.如权利要求1所述的去甲二氢愈创木酸在制备MCR-1酶抑制剂中应用，其特征在于去甲二氢愈创木酸与多粘菌素E联用在制备用于治疗MCR-1阳性大肠杆菌、MCR-1阳性沙门氏菌和MCR-1阳性肺炎克雷伯菌感染引起疾病的药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110524966.5A CN113209058B (zh) | 2021-05-14 | 2021-05-14 | 去甲二氢愈创木酸在制备mcr-1酶抑制剂中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110524966.5A CN113209058B (zh) | 2021-05-14 | 2021-05-14 | 去甲二氢愈创木酸在制备mcr-1酶抑制剂中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113209058A true CN113209058A (zh) | 2021-08-06 |
| CN113209058B CN113209058B (zh) | 2022-06-17 |
Family
ID=77095663
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110524966.5A Active CN113209058B (zh) | 2021-05-14 | 2021-05-14 | 去甲二氢愈创木酸在制备mcr-1酶抑制剂中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113209058B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115708824A (zh) * | 2022-11-28 | 2023-02-24 | 华南农业大学 | 7,8-二羟基黄酮作为铁稳态扰动剂在制备多粘菌素增效剂中的应用 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5409690A (en) * | 1993-06-23 | 1995-04-25 | Chemex Pharmaceuticals, Inc. | Treatment of multidrug resistant diseases in cancer cell by potentiating with masoprocol |
| CN105307648A (zh) * | 2013-05-02 | 2016-02-03 | 赫尔普百治疗有限公司 | 去甲二氢愈创木酸和氨基糖苷的组合 |
| CN107320466A (zh) * | 2017-08-16 | 2017-11-07 | 吉林大学 | 厚朴酚在制备ndm‑1酶抑制剂中的医用用途 |
| CN107548303A (zh) * | 2014-12-18 | 2018-01-05 | 赫尔普百治疗有限公司 | 抗微生物组合和其在治疗微生物感染中的用途 |
| CN109464439A (zh) * | 2019-01-10 | 2019-03-15 | 吉林大学 | 蛇床子素在制备mcr-1酶抑制剂中的应用 |
| CN110478337A (zh) * | 2019-10-06 | 2019-11-22 | 吉林大学 | 和厚朴酚及厚朴酚在制备mcr-1酶抑制剂中的应用 |
| US20200305423A1 (en) * | 2019-03-25 | 2020-10-01 | Arizona Board Of Regents On Behalf Of Arizona State University | Rapid drug discovery methods for pathogen inactivation |
-
2021
- 2021-05-14 CN CN202110524966.5A patent/CN113209058B/zh active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5409690A (en) * | 1993-06-23 | 1995-04-25 | Chemex Pharmaceuticals, Inc. | Treatment of multidrug resistant diseases in cancer cell by potentiating with masoprocol |
| CN105307648A (zh) * | 2013-05-02 | 2016-02-03 | 赫尔普百治疗有限公司 | 去甲二氢愈创木酸和氨基糖苷的组合 |
| CN107548303A (zh) * | 2014-12-18 | 2018-01-05 | 赫尔普百治疗有限公司 | 抗微生物组合和其在治疗微生物感染中的用途 |
| CN107320466A (zh) * | 2017-08-16 | 2017-11-07 | 吉林大学 | 厚朴酚在制备ndm‑1酶抑制剂中的医用用途 |
| CN109464439A (zh) * | 2019-01-10 | 2019-03-15 | 吉林大学 | 蛇床子素在制备mcr-1酶抑制剂中的应用 |
| US20200305423A1 (en) * | 2019-03-25 | 2020-10-01 | Arizona Board Of Regents On Behalf Of Arizona State University | Rapid drug discovery methods for pathogen inactivation |
| CN110478337A (zh) * | 2019-10-06 | 2019-11-22 | 吉林大学 | 和厚朴酚及厚朴酚在制备mcr-1酶抑制剂中的应用 |
Non-Patent Citations (6)
| Title |
|---|
| SUN J R，等: "Phenotype microarray analysis of the AdeRS two-component system in Acinetobacter baumannii", 《EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES》 * |
| YAN GUO，等: "Honokiol Restores Polymyxin Susceptibility to MCR-1-Positive Pathogens both In Vitro and In Vivo", 《APPL ENVIRON MICROBIOL》 * |
| YONGLIN ZHOU，等: "Discovery of a potential MCR-1 inhibitor that reverses polymyxin activity against clinical mcr-1-positive Enterobacteriaceae", 《J INFECT》 * |
| 卢娜，等: "丹皮酚恢复多粘菌素B对产MCR-1细菌的抗菌活性", 《中国畜牧兽医学会兽医药理毒理学分会第十五次学术讨论会论文集》 * |
| 詹宛莹，等: "去甲二氢愈创木酸逆转外排泵系统MexCD-OprJ介导铜绿假单胞菌对头孢他啶的耐药性及相关机制研究", 《中草药》 * |
| 邹夏慧: "中药抗肿瘤作用的分子机制研究进展", 《国外医学.中医中药分册》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115708824A (zh) * | 2022-11-28 | 2023-02-24 | 华南农业大学 | 7,8-二羟基黄酮作为铁稳态扰动剂在制备多粘菌素增效剂中的应用 |
| CN115708824B (zh) * | 2022-11-28 | 2023-11-21 | 华南农业大学 | 7,8-二羟基黄酮作为铁稳态扰动剂在制备多粘菌素增效剂中的应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113209058B (zh) | 2022-06-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Assane et al. | Combination of antimicrobials as an approach to reduce their application in aquaculture: Emphasis on the use of thiamphenicol/florfenicol against Aeromonas hydrophila | |
| CN109999027B (zh) | 褪黑素的用途 | |
| CN102920771B (zh) | 一种用于治疗家禽球虫病的药物 | |
| CN113209058A (zh) | 去甲二氢愈创木酸在制备mcr-1酶抑制剂中的应用 | |
| CN110269857A (zh) | 含阿维巴坦的抗菌组合物及其用途 | |
| CN110974814A (zh) | 双硫仑在细菌感染疾病中的潜在应用 | |
| US11752120B2 (en) | Use of succinic acid in increasing sensitivity of bacteria to antibiotics | |
| CN107714678B (zh) | 紫檀芪在制备mcr-1酶抑制剂中的应用 | |
| CN105853449B (zh) | 一种注射用硫酸阿米卡星的抗菌组合药物 | |
| CN113384587A (zh) | 委陵菜酸在制备碳青霉烯酶抑制剂中的应用 | |
| EP3733176B1 (en) | Composition comprising piperacillin, pharmaceutical preparation thereof and use thereof | |
| CN107875154B (zh) | 含有哌拉西林的组合物、其药物制剂及其应用 | |
| CN102349897B (zh) | 一种美罗培南钠/他唑巴坦钠药物组合物 | |
| CN105998029A (zh) | 一种注射用盐酸左氧氟沙星的抗菌组合药物 | |
| RU2614730C1 (ru) | Антибактериальное средство и способ лечения кишечного иерсиниоза, или псевдотуберкулеза, или эшерихиоза | |
| CN109331025A (zh) | 羟氯扎胺在制备抗猪链球菌的药物中的应用 | |
| CN115990148B (zh) | α-侧柏酮在制备治疗碳青霉烯类抗生素耐药菌感染药物中的应用 | |
| KR102208837B1 (ko) | 메틸 갈레이트 및 플로로퀴놀론 계열 항균제를 포함하는 박테리아의 장 부착, 침입 억제, 또는 항생제 내성 억제용 조성물 | |
| CN110237113B (zh) | 一种抗大肠杆菌与球虫混合感染的植物提取物添加剂及应用 | |
| Febriza et al. | Curcumin Effects in Inducing Vitamin D Receptor (VDR) and Inhibiting of Salmonella typhi Growth in vivo | |
| KR102441377B1 (ko) | 펙토리나린을 포함하는 바이오필름 형성 억제용 조성물 | |
| CN102228458B (zh) | 一种美罗培南和舒巴坦钠的药物组合物 | |
| CN108066352A (zh) | 黄芩苷在制备水产动物链球菌病防治药物中的用途 | |
| CN101926846A (zh) | 一种治疗鸡白痢的药物组合物及其制备方法 | |
| JPH07126172A (ja) | Ｌｐｓを含む抗ｍｒｓａ剤及び動物用抗ｍｒｓａ剤 |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |