CN107714678B - 紫檀芪在制备mcr-1酶抑制剂中的应用 - Google Patents
紫檀芪在制备mcr-1酶抑制剂中的应用 Download PDFInfo
- Publication number
- CN107714678B CN107714678B CN201710992619.9A CN201710992619A CN107714678B CN 107714678 B CN107714678 B CN 107714678B CN 201710992619 A CN201710992619 A CN 201710992619A CN 107714678 B CN107714678 B CN 107714678B
- Authority
- CN
- China
- Prior art keywords
- mcr
- pterostilbene
- polymyxin
- combined
- positive
- 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.)
- Active
Links
- VLEUZFDZJKSGMX-ONEGZZNKSA-N pterostilbene Chemical compound COC1=CC(OC)=CC(\C=C\C=2C=CC(O)=CC=2)=C1 VLEUZFDZJKSGMX-ONEGZZNKSA-N 0.000 title claims abstract description 40
- VLEUZFDZJKSGMX-UHFFFAOYSA-N pterostilbene Natural products COC1=CC(OC)=CC(C=CC=2C=CC(O)=CC=2)=C1 VLEUZFDZJKSGMX-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 101150004219 MCR1 gene Proteins 0.000 title claims abstract description 39
- 229940125532 enzyme inhibitor Drugs 0.000 title claims abstract description 9
- 239000002532 enzyme inhibitor Substances 0.000 title claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 8
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 7
- 241000588914 Enterobacter Species 0.000 claims abstract description 5
- 208000015181 infectious disease Diseases 0.000 claims abstract description 5
- 108010040201 Polymyxins Proteins 0.000 claims description 17
- 241000588921 Enterobacteriaceae Species 0.000 claims description 6
- 208000035473 Communicable disease Diseases 0.000 claims description 3
- 108010093965 Polymyxin B Proteins 0.000 abstract description 13
- 229920000024 polymyxin B Polymers 0.000 abstract description 13
- 229960005266 polymyxin b Drugs 0.000 abstract description 13
- 241000588724 Escherichia coli Species 0.000 abstract description 11
- 241000699670 Mus sp. Species 0.000 abstract description 8
- 206010034674 peritonitis Diseases 0.000 abstract description 7
- 238000000034 method Methods 0.000 abstract description 6
- 241000588747 Klebsiella pneumoniae Species 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 5
- 108090000790 Enzymes Proteins 0.000 abstract description 4
- 102000004190 Enzymes Human genes 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 239000003112 inhibitor Substances 0.000 abstract description 4
- 238000004659 sterilization and disinfection Methods 0.000 abstract description 3
- 241000894006 Bacteria Species 0.000 abstract description 2
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 2
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 229940088710 antibiotic agent Drugs 0.000 abstract description 2
- 206010001427 Enterobacter infections Diseases 0.000 abstract 1
- 230000000797 effect on infection Effects 0.000 abstract 1
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- 231100000820 toxicity test Toxicity 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 230000001580 bacterial effect Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229940041153 polymyxins Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 241000305071 Enterobacterales Species 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000010172 mouse model Methods 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
- 241001133760 Acoelorraphe Species 0.000 description 1
- 240000001606 Adenanthera pavonina Species 0.000 description 1
- 235000011470 Adenanthera pavonina Nutrition 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 108010078777 Colistin Proteins 0.000 description 1
- 206010011409 Cross infection Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000034801 Enterobacteriaceae Infections Diseases 0.000 description 1
- 240000000851 Vaccinium corymbosum Species 0.000 description 1
- 235000003095 Vaccinium corymbosum Nutrition 0.000 description 1
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 235000021014 blueberries Nutrition 0.000 description 1
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 1
- 108010068385 carbapenemase Proteins 0.000 description 1
- 229940041011 carbapenems Drugs 0.000 description 1
- 229960003346 colistin Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 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 Chemical compound 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 description 1
- 230000001937 non-anti-biotic effect Effects 0.000 description 1
- 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 description 1
- KNIWPHSUTGNZST-UHFFFAOYSA-N polymyxin E2 Natural products CC(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 KNIWPHSUTGNZST-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 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
- 239000002023 wood Substances 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
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- 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
-
- 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)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及紫檀芪在制备MCR‑1酶抑制剂中的应用，并通过棋盘法和时间‑杀菌曲线法验证紫檀芪能够抑制MCR‑1酶的活性并恢复多粘菌素B对MCR‑1阳性肠杆菌(主要包括大肠杆菌和肺炎克雷伯菌)的抗菌活性。进一步通过建立小鼠腹膜炎感染模型证明紫檀芪联用多粘菌素B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，同时通过毒性实验证明紫檀芪药物浓度在治疗剂量内对小鼠无毒。因此紫檀芪作为MCR‑1抑制剂可以与抗生素联用，增加对超级耐药菌使用药物的选择性,对开发抗MCR‑1阳性肠杆菌感染新药有着重要意义。
Description
技术领域
本发明公开了紫檀芪的一种新的用途，进一步讲涉及紫檀芪在制备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
细菌耐药性的不断增加，以近几年出现的产碳青霉烯酶的革兰氏阴性肠杆菌感染所导致的病情较为严重，耐药菌感染导致碳青霉烯类抗生素的治疗失败和较高的死亡率，给治疗院内感染、特别是治疗ICU感染带来了更大的压力。这迫使人们使用多粘菌素这一古老的抗生素来防治耐碳青霉烯类抗生素的肠杆菌。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治。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。
紫檀芪是一种来源于紫檀、蓝莓、葡萄和花榈木等植物的有效成分。紫檀芪有抗癌、抗炎、抗氧化和镇痛剂的作用。目前大量研究表明紫檀芪在皮肤疾病的治疗和防护中有较好的作用，特别是在抗氧化等领域。但截至目前国内外未见紫檀芪在制备MCR-1抑制剂中的相关报道。
发明内容
本发明提供了一种紫檀芪在制备MCR-1酶抑制剂中的医用用途，公开了紫檀芪能够抑制MCR-1酶的活性，恢复多粘菌素对MCR-1大肠杆菌的杀菌活性。
本发明所述的紫檀芪，其分子式：C16H16O3，分子量：256.30；
本发明所述的多粘菌素包括多粘菌素B和粘菌素的硫酸盐，其分子式分别为：C56H100N16O17S和C53H100N16O13·2.5H2SO4；
分子量分别为：1301.56和1414.00。
本发明通过棋盘法和时间-杀菌曲线法验证紫檀芪能够抑制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，试验所用肠杆菌主要包括MCR-1阳性大肠杆菌和肺炎克雷伯菌。进一步通过建立小鼠腹膜炎感染模型证明紫檀芪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：
提供了紫檀芪在制备MCR-1酶抑制剂中的新医用用途，公开了紫檀芪能够抑制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，紫檀芪联用多粘菌素对表达MCR-1的细菌性感染，尤其是MCR-1阳性肠杆菌引起的腹膜炎等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为本发明紫檀芪联合多粘菌素B对MCR-1阳性大肠杆菌的时间-杀菌曲线；
图2为本发明紫檀芪联合多粘菌素B对小鼠治疗实验。
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。
实施例1
紫檀芪作为MCR-1酶抑制剂用于药学上可接受的任何载体。
实施例2
紫檀芪作为MCR-1酶抑制剂用于制备治疗感染性疾病的药物。
实施例3
紫檀芪作为MCR-1酶抑制剂用于治疗细菌引起的感染性疾病，特别是MCR-1阳性肠杆菌引起的感染。
试验例1
最小抑菌浓度试验
于96孔无菌微孔板内按棋盘法进行紫檀芪、多粘菌素单用及二者联用抗产MCR-1大肠杆菌和肺炎克雷伯菌的抑菌活性实验，确定二者单独应用及联合应用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(紫檀芪联合)/MIC(紫檀芪单用)，结果见表1：
表1紫檀芪联用多粘菌素对MCR-1阳性大肠杆菌分离株的MIC及FIC值
结论：紫檀芪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阳性肺炎克雷伯菌MIC值16倍，FICI数值表明二者具有协同作用。
试验例2
时间-杀菌曲线试验
取MCR-1阳性大肠杆菌分离株过夜培养物，调整至5×107CFUs/mL，备用。取无菌试管3组(无抗生素对照组、2μg/mL多粘菌素B组及32μg/mL紫檀芪联用2μg/mL多粘菌素B组)，每组标记为1、3、5、7h，所有试管内均加入1mL高压灭菌的LB培养基，之后，每管内均加入10μL调整后的菌液，使每个试管内的菌液浓度为5×105CFUs/mL。其中2μg/mL多粘菌素B组及32μg/mL紫檀芪联用2μg/mL多粘菌素B组分别加入对应用量的抗生素及抑制剂，混匀之后立即将无抗生素对照组的菌液进行涂板计数，作为0h的菌落数。之后，每1、3、5及7h分别取对应试管内的菌液，涂板计数，绘制时间-杀菌曲线(图1)。
结论：紫檀芪联用多粘菌素能够在1h内彻底杀死MCR-1阳性肠杆菌。
试验例3
小鼠腹膜炎的实验治疗学研究
小鼠大肠杆菌腹膜炎模型
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(2×108CFUs)，建立小鼠腹膜炎的模型。
保护率试验
小鼠腹腔接种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B、腹腔注射80mg/kg(50μl)的紫檀芪DMSO溶液，及多粘菌素B(5mg/kg)联用紫檀芪(80mg/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，腹腔给予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，分别记录小鼠感染MCR-1阳性大肠杆菌5天后的死亡率(每隔12小时记录)，结果见附图2。
结论：经紫檀芪联用多粘菌素B治疗后，显著降低小鼠腹膜炎的死亡率，紫檀芪或多粘菌素B单独治疗组不具有显著的保护效果。
Claims (1)
1.紫檀芪与多黏菌素联合在制备治疗MCR-1阳性肠杆菌引起的感染性疾病药物中的用途，其特征在于紫檀芪作为MCR-1酶抑制剂，能够恢复多粘菌素对MCR-1阳性肠杆菌的杀菌活性。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710992619.9A CN107714678B (zh) | 2017-10-23 | 2017-10-23 | 紫檀芪在制备mcr-1酶抑制剂中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710992619.9A CN107714678B (zh) | 2017-10-23 | 2017-10-23 | 紫檀芪在制备mcr-1酶抑制剂中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107714678A CN107714678A (zh) | 2018-02-23 |
| CN107714678B true CN107714678B (zh) | 2020-06-02 |
Family
ID=61213263
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710992619.9A Active CN107714678B (zh) | 2017-10-23 | 2017-10-23 | 紫檀芪在制备mcr-1酶抑制剂中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107714678B (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108159029B (zh) * | 2018-03-09 | 2019-10-11 | 邓旭明 | 紫檀芪在制备ndm-1酶抑制剂中的应用 |
| CN108553459B (zh) * | 2018-05-22 | 2019-10-11 | 中山大学 | 一种mcr-1抑制剂及其在制备抑制mcr-1阳性耐药菌药物中的应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016216419A (ja) * | 2015-05-25 | 2016-12-22 | 学校法人近畿大学 | 歯周病改善剤及びその製造方法 |
| CN106615071A (zh) * | 2016-12-20 | 2017-05-10 | 中国农业大学 | 紫檀芪在防治葡萄灰霉病和荔枝霜疫霉病中的应用 |
| JP2017081831A (ja) * | 2015-10-23 | 2017-05-18 | ライオン株式会社 | 口腔用抗菌剤及び口腔用組成物 |
-
2017
- 2017-10-23 CN CN201710992619.9A patent/CN107714678B/zh active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016216419A (ja) * | 2015-05-25 | 2016-12-22 | 学校法人近畿大学 | 歯周病改善剤及びその製造方法 |
| JP2017081831A (ja) * | 2015-10-23 | 2017-05-18 | ライオン株式会社 | 口腔用抗菌剤及び口腔用組成物 |
| CN106615071A (zh) * | 2016-12-20 | 2017-05-10 | 中国农业大学 | 紫檀芪在防治葡萄灰霉病和荔枝霜疫霉病中的应用 |
Non-Patent Citations (1)
| Title |
|---|
| Bactericidal Effect of Pterostilbene Alone and in;Wee Xian Leed等;《Molecules》;20170317;第22卷(第3期);第463页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107714678A (zh) | 2018-02-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2021068614A1 (zh) | 和厚朴酚及厚朴酚在制备mcr-1酶抑制剂中的应用 | |
| JP2018513188A5 (zh) | ||
| US11965006B2 (en) | Antimicrobial and anti-cancer therapy | |
| CN107714678B (zh) | 紫檀芪在制备mcr-1酶抑制剂中的应用 | |
| CN109464439B (zh) | 蛇床子素在制备mcr-1酶抑制剂中的应用 | |
| CN107320466A (zh) | 厚朴酚在制备ndm‑1酶抑制剂中的医用用途 | |
| CN103933350B (zh) | 白及乙酸乙酯提取物的用途 | |
| WO2021198940A1 (ja) | ヒト又は動物の慢性若しくは急性のウイルス感染症及び／又は敗血症の予防若しくは治療のための組成物 | |
| CN113209058B (zh) | 去甲二氢愈创木酸在制备mcr-1酶抑制剂中的应用 | |
| CN116617361A (zh) | 百里香酚在制备mcr-1酶抑制剂中的应用 | |
| CN112957354B (zh) | 小白菊内酯在制备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 | |
| CN102988765B (zh) | 白及乙酸乙酯提取物的用途 | |
| US20220339206A1 (en) | Compositions and methods for treatment of conditions using fractionated honey | |
| CN102920718B (zh) | 苯乙醇苷类单体化合物的应用 | |
| US11534438B2 (en) | Composition containing piperacillin, pharmaceutical formulation thereof and use thereof | |
| CN105998029A (zh) | 一种注射用盐酸左氧氟沙星的抗菌组合药物 | |
| CN108159029B (zh) | 紫檀芪在制备ndm-1酶抑制剂中的应用 | |
| CN114917285B (zh) | 一种多糖化合物在预防和治疗呼吸道病毒感染药物中的应用 | |
| US20210268075A1 (en) | Pharmaceutical composition and method of treatment using serratiopeptidase, mannose or its derivative, and optionally antinfection agents | |
| CN113456641B (zh) | 一种化合物在制备抗真菌药物中的应用 | |
| CN102727509A (zh) | 黄芩苷在制备治疗肺炎药物中的应用 | |
| CN112336777B (zh) | 一种抑制耐药菌活性的药物 | |
| TWI446902B (zh) | 一種化合物之用途, 其係用於製備治療敗血性休克之藥物 | |
| KR20240143825A (ko) | 항진균제에 대한 시너지 효과를 갖는 플루오로퀴놀론계 화합물 및 이의 용도 |
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 |