CN103479636A - Lycojaponicumin C在抗人体真菌药物中的应用 - Google Patents
Lycojaponicumin C在抗人体真菌药物中的应用 Download PDFInfo
- Publication number
- CN103479636A CN103479636A CN201310441893.9A CN201310441893A CN103479636A CN 103479636 A CN103479636 A CN 103479636A CN 201310441893 A CN201310441893 A CN 201310441893A CN 103479636 A CN103479636 A CN 103479636A
- Authority
- CN
- China
- Prior art keywords
- lycojaponicumin
- preparation
- human
- fungi
- application
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 15
- UULHZQYEEKIMDO-CLROSIBMSA-N lycojaponicumin C Natural products CN1CCC[C@@]23[C@@H]1CC[C@]24[C@@H](CC3=O)C(=CCC4=O)C UULHZQYEEKIMDO-CLROSIBMSA-N 0.000 title abstract description 22
- 241000233866 Fungi Species 0.000 title abstract description 17
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 229940079593 drug Drugs 0.000 title abstract 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 229930185194 lycojaponicumin Natural products 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 7
- 241001480048 Trichophyton tonsurans Species 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract 2
- 241001480037 Microsporum Species 0.000 abstract 1
- 241000223229 Trichophyton rubrum Species 0.000 abstract 1
- 208000024386 fungal infectious disease Diseases 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000927897 Lycopodium japonicum Species 0.000 description 2
- 241000893980 Microsporum canis Species 0.000 description 2
- 241000223238 Trichophyton Species 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229960004125 ketoconazole Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229960004821 amikacin Drugs 0.000 description 1
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229960004130 itraconazole Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 description 1
- 229960002722 terbinafine Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 description 1
- 229960004740 voriconazole Drugs 0.000 description 1
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及Lycojaponicumin C在制备抗人体真菌药物中的应用，属于医药领域。Lycojaponicumin C具有很强的抑制红色毛癣菌、羊毛状小孢子菌或断发癣菌的作用，因此Lycojaponicumin C可作为具有抗人体真菌的化合物，并有望在制备相关药物中得到应用。本发明涉及的Lycojaponicumin C在制备治疗抗人体真菌药物中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其对于人体真菌抑制活性强得意想不到，不存在由其他化合物给出任何启示的可能，具备突出的实质性特点，同时用于人体真菌感染的防治显然具有显著的进步。
Description
技术领域
本发明涉及Lycojaponicumin C的用途，尤其涉及Lycojaponicumin C在制备抗人体真菌药物中的应用。
背景技术
致病菌的扩散及其耐药性的增强严重威胁着人类的健康和生命，抗菌药物已作为常规用药广泛用于艾滋病、器官移植以及慢性消耗性疾病（如癌症、糖尿病、尿毒症等）的治疗，虽然目前临床上使用的抗菌药剂（如酮康唑、阿米卡星、庆大霉素、活力康唑、伊曲康唑、特比萘芬、二性霉素、氟康唑等）对皮肤及浅表部位感染的疗效较好，但这些抗菌药物的蓄积毒性较强，常常引起肝肾损伤、消化道刺激、头晕、过敏等，所以寻找作用机理独特的新型抗菌药物成为当今药物研发的热点之一。
本发明涉及的化合物Lycojaponicumin C是一个2012年发表（Wang,X.J.et al.,2012.Lycojaponicumins A-C,Three Alkaloids with an Unprecedented Skeleton from Lycopodium japonicum.Organic Letters14(10),2614-2617.）的新骨架化合物，该化合物拥有全新的骨架类型，对于本发明涉及的Lycojaponicumin C在制备治疗抗人体真菌药物中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其对于人体真菌抑制活性强得意想不到，不存在由其他化合物给出任何启示的可能，具备突出的实质性特点，同时用于人体真菌感染的防治显然具有显著的进步。
发明内容
本发明的目的在于：
提供一种本发明的Lycojaponicumin C在制备抗人体真菌药物中的应用。
所述化合物Lycojaponicumin C结构如式（Ⅰ）所示：
Lycojaponicumin C具有很强的抑制红色毛癣菌、羊毛状小孢子菌或断发癣菌的作用，所以Lycojaponicumin C可作为具有抗人体真菌作用的化合物，并有望在制备抗人体真菌药物中得到应用。
本发明涉及的Lycojaponicumin C在制备治疗抗人体真菌药物中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其对于人体真菌抑制活性强得意想不到，不存在由其他化合物给出任何启示的可能，具备突出的实质性特点，同时用于人体真菌感染的防治显然具有显著的进步。
具体实施方式
本发明所涉及化合物Lycojaponicumin C的制备方法参见文献（Wang,X.J.et al.,2012.Lycojaponicumins A-C,Three Alkaloids with an Unprecedented Skeleton from Lycopodium japonicum.Organic Letters 14(10),2614-2617.）。
以下通过实施例对本发明作进一步详细的说明，但本发明的保护范围不受具体实施例的任何限制，而是由权利要求加以限定。
实施例1：本发明所涉及化合物Lycojaponicumin C片剂的制备：
取20克化合物Lycojaponicumin C，加入制备片剂的常规辅料180克，混匀，常规压片机制成1000片。
实施例2：本发明所涉及化合物Lycojaponicumin C胶囊剂的制备：
取20克化合物Lycojaponicumin C，加入制备胶囊剂的常规辅料如淀粉180克，混匀，装胶囊制成1000片。
下面通过药效学实验来进一步说明其药物活性。
实验例：Lycojaponicumin C抗人体真菌活性
抗人体真菌活性实验是采用浓度稀释的方法，每次测定重复三次，测试病原菌有红色毛癣菌、羊毛状小孢子菌和断发癣菌，菌液浓度为105个/mL。Lycojaponicumin C起始浓度为50.0μg/mL（5％二甲基亚砜DMSO），梯度稀释至0.098μg/mL，等量体积的菌液和测试样品混合培养在96孔板中，人体真菌培养温度分别为28℃，培养时间24h后观察，若发现没有菌落形成时为样品最低抗人体真菌浓度，即MIC值。该实验阳性对照为酮康唑，Lycojaponicumin C抗人体真菌结果见表1。
表1Lycojaponicumin C抗人体真菌MIC值（μg/mL）
结论：Lycojaponicumin C具有很强的抗人体真菌活性，因此本发明的Lycojaponicumin C有望被用于制备新型抗人体真菌药物。
Claims (1)
1.Lycojaponicumin C在抗人体真菌药物中的应用，所述化合物Lycojaponicumin C结构如式（Ⅰ）所示：
式（Ⅰ）。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310441893.9A CN103479636B (zh) | 2013-09-23 | 2013-09-23 | Lycojaponicumin C在制备抗人体真菌药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310441893.9A CN103479636B (zh) | 2013-09-23 | 2013-09-23 | Lycojaponicumin C在制备抗人体真菌药物中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103479636A true CN103479636A (zh) | 2014-01-01 |
| CN103479636B CN103479636B (zh) | 2015-08-19 |
Family
ID=49820459
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310441893.9A Expired - Fee Related CN103479636B (zh) | 2013-09-23 | 2013-09-23 | Lycojaponicumin C在制备抗人体真菌药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103479636B (zh) |
-
2013
- 2013-09-23 CN CN201310441893.9A patent/CN103479636B/zh not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| XIAO-JING WANG, ET AL.: "Lycojaponicumins A-c,Three Alkaloids with an Unprecedented Skeleton from Lycopodium japonicum", 《ORGANIC LETTERS》, vol. 14, no. 10, 8 May 2012 (2012-05-08), pages 2614 - 2617, XP055066237, DOI: 10.1021/ol3009478 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103479636B (zh) | 2015-08-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103462989A (zh) | Sarcaboside B在抗人体真菌药物中的应用 | |
| CN103446135B (zh) | Lycojaponicumin A在制备抗人体真菌药物中的应用 | |
| CN103479636B (zh) | Lycojaponicumin C在制备抗人体真菌药物中的应用 | |
| CN102872059B (zh) | Gypensapogenin B在制备抗人体真菌药物中的应用 | |
| CN102861087B (zh) | Houttuynoid D在抗人体真菌药物中的应用 | |
| CN103463029B (zh) | Lycojaponicumin B在制备抗人体真菌药物中的应用 | |
| CN103446115A (zh) | Sarcaboside A在抗人体真菌药物中的应用 | |
| CN103479608A (zh) | Scopariusins在制备抗人体真菌药物中的应用 | |
| CN102861083B (zh) | Houttuynoid B在抗人体真菌药物中的应用 | |
| CN103446125B (zh) | Lycojaponicumin B在制备抗细菌药物中的应用 | |
| CN102872133B (zh) | Houttuynoid E在抗人体真菌药物中的应用 | |
| CN103372004B (zh) | Chukrasone B在制备抗人体真菌药物中的应用 | |
| CN102872007A (zh) | Eryngiolide A在抗人体真菌药物中的应用 | |
| CN102872030B (zh) | Gypensapogenin B在制备抗细菌药物中的应用 | |
| CN103462968B (zh) | Incarviatone A在制备抗细菌药物中的应用 | |
| CN103393696B (zh) | Chukrasone A在制备抗人体真菌药物中的应用 | |
| CN102872145B (zh) | Houttuynoid C在抗人体真菌药物中的应用 | |
| CN102861027B (zh) | Gypensapogenin A在抗人体真菌药物中的应用 | |
| CN103463037B (zh) | Lycojaponicumin A在制备抗细菌药物中的应用 | |
| CN103463075B (zh) | Lycojaponicumin C在制备抗细菌药物中的应用 | |
| CN103446095A (zh) | Incarviatone A在抗人体真菌药物中的应用 | |
| CN102895250A (zh) | Houttuynoid A在抗人体真菌药物中的应用 | |
| CN102988345A (zh) | Aphanamixoid A在制备抗人体真菌药物中的应用 | |
| CN103446114A (zh) | Sarcaboside A在抗细菌药物中的应用 | |
| CN103463107A (zh) | Phyllanthoid A在制备抗人体真菌药物中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhang Junmin Inventor before: Wu Junhua Inventor before: Wang Hui |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20171127 Address after: 236300 Anhui city of Fuyang province Funan County Duan Ying Xiang Duan Ying Cun east section of No. 7 Patentee after: Zhang Junmin Address before: Metro Technology Building No. 69 Olympic Avenue in Jianye District of Nanjing city in Jiangsu province 210019 01 5 storey buildings Patentee before: Nanjing Guangkangxie Biomedical Technology Co., Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150819 Termination date: 20180923 |