CN106983741B - 氰基丙烯酸酯类化合物在制备治疗人畜真菌性感染疾病的药物中的应用 - Google Patents
氰基丙烯酸酯类化合物在制备治疗人畜真菌性感染疾病的药物中的应用 Download PDFInfo
- Publication number
- CN106983741B CN106983741B CN201710338081.XA CN201710338081A CN106983741B CN 106983741 B CN106983741 B CN 106983741B CN 201710338081 A CN201710338081 A CN 201710338081A CN 106983741 B CN106983741 B CN 106983741B
- Authority
- CN
- China
- Prior art keywords
- cyano
- amino
- phenylacrylate
- application
- cyanoacrylate compounds
- 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
- NLCKLZIHJQEMCU-UHFFFAOYSA-N cyano prop-2-enoate Chemical class C=CC(=O)OC#N NLCKLZIHJQEMCU-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 title claims description 8
- 229940079593 drug Drugs 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 4
- 241001465754 Metazoa Species 0.000 title description 6
- 208000024386 fungal infectious disease Diseases 0.000 title 1
- 208000015181 infectious disease Diseases 0.000 claims abstract description 10
- 208000031295 Animal disease Diseases 0.000 claims abstract description 8
- 230000002458 infectious effect Effects 0.000 claims abstract description 6
- 208000017520 skin disease Diseases 0.000 claims abstract description 4
- -1 2-cyano- 3-amino-3-phenylacrylate methyl ester Chemical compound 0.000 claims description 15
- 241000233866 Fungi Species 0.000 claims description 8
- YKRQBWKLHCEKQH-UHFFFAOYSA-N ethyl 3-amino-2-cyano-3-phenylprop-2-enoate Chemical compound CCOC(=O)C(C#N)=C(N)C1=CC=CC=C1 YKRQBWKLHCEKQH-UHFFFAOYSA-N 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000002674 ointment Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 229920001651 Cyanoacrylate Polymers 0.000 claims 3
- 239000006072 paste Substances 0.000 claims 2
- 239000002775 capsule Substances 0.000 claims 1
- 230000003111 delayed effect Effects 0.000 claims 1
- 239000008298 dragée Substances 0.000 claims 1
- 239000008187 granular material Substances 0.000 claims 1
- 239000012669 liquid formulation Substances 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 208000010195 Onychomycosis Diseases 0.000 abstract description 3
- 206010031252 Osteomyelitis Diseases 0.000 abstract description 3
- 206010003246 arthritis Diseases 0.000 abstract description 3
- 206010014801 endophthalmitis Diseases 0.000 abstract description 3
- 206010023332 keratitis Diseases 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 201000009890 sinusitis Diseases 0.000 abstract description 3
- 201000005882 tinea unguium Diseases 0.000 abstract description 3
- 241000894006 Bacteria Species 0.000 abstract description 2
- 208000027954 Poultry disease Diseases 0.000 abstract 1
- 208000025865 Ulcer Diseases 0.000 abstract 1
- 210000004087 cornea Anatomy 0.000 abstract 1
- 231100000397 ulcer Toxicity 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 208000031888 Mycoses Diseases 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- 206010017533 Fungal infection Diseases 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 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 4
- 229960004740 voriconazole Drugs 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 2
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=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-KKGHZKTASA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 241000223218 Fusarium Species 0.000 description 2
- 241000223195 Fusarium graminearum Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241000041810 Mycetoma Species 0.000 description 2
- 101710204026 Myosin-5 Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 206010064996 Ulcerative keratitis Diseases 0.000 description 2
- 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 2
- 229960003942 amphotericin b Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 201000007717 corneal ulcer Diseases 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 231100000243 mutagenic effect Toxicity 0.000 description 2
- 230000003505 mutagenic effect Effects 0.000 description 2
- 231100000344 non-irritating Toxicity 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XOMRRQXKHMYMOC-NRFANRHFSA-N (3s)-3-hexadecanoyloxy-4-(trimethylazaniumyl)butanoate Chemical compound CCCCCCCCCCCCCCCC(=O)O[C@@H](CC([O-])=O)C[N+](C)(C)C XOMRRQXKHMYMOC-NRFANRHFSA-N 0.000 description 1
- IJVRPNIWWODHHA-UHFFFAOYSA-N 2-cyanoprop-2-enoic acid Chemical class OC(=O)C(=C)C#N IJVRPNIWWODHHA-UHFFFAOYSA-N 0.000 description 1
- 238000010953 Ames test Methods 0.000 description 1
- 231100000039 Ames test Toxicity 0.000 description 1
- 208000031404 Chromosome Aberrations Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 206010051792 Infusion related reaction Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 206010029155 Nephropathy toxic Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 231100000005 chromosome aberration Toxicity 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960004413 flucytosine Drugs 0.000 description 1
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 125000000623 heterocyclic group Chemical class 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 231100000286 mucous membrane, eye irritation or corrosion testing Toxicity 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及氰基丙烯酸酯类化合物在治疗真菌引起的感染性人畜疾病上的应用，特别是由镰刀菌引起的皮肤病，角膜炎，角膜溃疡，内眼炎、骨髓炎、关节炎、鼻窦感染、甲真菌病、足菌肿及手术或烧伤过程感染等人、畜疾病。
Description
技术领域：
本发明涉及治疗真菌感染的人畜疾病领域，具体的为涉及氰基丙烯酸酯类化合物在治疗真菌引起的感染性人畜疾病上的应用。
背景技术：
近30年来，由真菌感染引起的人畜皮肤病例急剧增加，从而导致对新的抗真菌药剂的需求变得更加迫切，目前用于治疗真菌感染的药物包括两性霉素B，氟胞嘧啶，伏立康唑等。两性霉素B因输注-相关的反应和肾毒性而受到限制，伏立康唑因其溶解性不能克服，限制了其使用范围。因此，有必要开发出新的抗真菌的药物用于皮肤病的治疗。
氰基丙烯酸酯类化合物是指分子靶标为肌球蛋白的2-氰基-3-氨基-3-苯基丙烯酸酯甲酯、2-氰基-3-氨基-3-苯基丙烯酸酯乙酯(又称：氰烯菌酯，试验号： JS399-19)和2-氰基-3-氨基-3-苯基丙烯酸酯丙酯。其中2-氰基-3-氨基-3-苯基丙烯酸酯乙酯(氰烯菌酯)是由国家南方农药创制中心江苏基地于1998年合成、并由南京农业大学周明国教授团队发现是具有肌球蛋白抑制作用的镰刀菌专化活性的化合物，对与禾谷镰刀菌(Fusariumgraminearum)肌球蛋白-5(Myosin-5) 具有80％以上同源性的真菌具有较高抗菌活性。该化合物已经注册用于小麦赤霉病和水稻恶苗病等镰刀菌引起的农作物真菌病害防治。但至今还没有文献报道过其医药和兽药活性，特别是用于治疗真菌感染性人畜疾病上的用途。
经南京医科大学卫生分析检测中心应用毒理研究所检测。氰烯菌酯原药急性毒性五项检测结果分别为：雄性大鼠急性经口LD50＞5000mg/kg；雌性大鼠急性进口LD50＞5000mg/kg；属微毒类；雄性大鼠急性经皮LD50＞5000mg/kg；雌性大鼠急性进皮LD50＞5000mg/kg；属微毒类；眼刺激试验为1.5(1h)，对眼无刺激性。(1∶100稀释)；皮肤刺激试验为0(4h)，对皮肤无刺激性；致敏试验：属微致敏物。氰烯菌酯原药致突变检测结果为：AMES试验：平板渗入法，剂量达2500μg/皿，加及不加S9，对测试标准菌TA97a、TA98、TA100和TA102均未检出明显的诱变活性；小鼠骨髓嗜多染红细胞微核试验：雌雄小鼠剂量分别达到250和400mg/kgb.wt.未检出对雌雄小鼠骨髓嗜多染红细胞的诱变活性；小鼠睾丸精母细胞染色体畸变分析：剂量达400mg/kgb.wt.未检出对雄小鼠睾丸精母细胞染色体的诱变活性。经上述毒性测验表明：氰烯菌酯对人类和动物安全，可以用于人类和动物感染性疾病的治疗。
发明内容：
为了克服现有技术的不足，本发明首要目的在于提供一种治疗真菌性感染的人畜用药物，特别的本发明涉及氰基丙烯酸酯类化合物用于治疗真菌感染的人畜疾病用途，特别是皮肤病、角膜炎、角膜溃疡、内眼炎、骨髓炎、关节炎、鼻窦感染、甲真菌病、足菌肿及手术或烧伤过程感染等疾病。氰基丙烯酸类化合物结构通式如下：
R＝苯、取代苯、杂环；x＝1～5；y＝3～11
本发明的目的是通过下述技术方案实现的：
氰基丙烯酸酯类化合物在治疗真菌引起的感染性疾病上的应用，所述氰基丙烯酸酯类化合物是2-氰基-3-氨基-3-苯基丙烯酸酯甲酯、2-氰基-3-氨基-3-苯基丙烯酸酯乙酯(又称：氰烯菌酯，试验号：JS399-19)和2-氰基-3-氨基-3-苯基丙烯酸酯丙酯。其化学结构式分别如下。
氰基丙烯酸酯类化合物在治疗真菌引起的感染性人畜疾病是角膜炎、角膜溃疡、内眼炎、骨髓炎、关节炎、鼻窦感染、甲真菌病、足菌肿及手术或烧伤过程感染等疾病；本发明的氰基丙烯酸酯类化合物是加工成固体、液体和膏状制剂，通过口服、注射、涂抹或冲洗患处的形式给药。
具体实施方案：
动物实验：
提供皮肤感染的小鼠，用药剂(0.5ppm)进行皮下注射处理，连续7天观察皮肤的变化。结果见表1。
表1氰基丙烯酸酯类化合物对小鼠感染的治疗效果
| 处理 | 治疗效果 |
| 2-氰基-3-氨基-3-苯基丙烯酸酯甲酯 | ※※※※ |
| 2-氰基-3-氨基-3-苯基丙烯酸酯乙酯 | ※※※※ |
| 2-氰基-3-氨基-3-苯基丙烯酸酯丙酯 | ※※※※ |
| 伏立康唑 | ※※※※ |
| 生理盐水 | ※ |
表1中“※”表示受感染的皮肤直径在5cm以上，“※※”表示受感染的皮肤直径在3-5cm，“※※※”表示受感染的皮肤直径在1-3cm，“※※※※”表示观察不到病理变化(治愈)。从表1的结果可知，氰基丙烯酸酯类化合物对感染的治疗效果和伏立康唑相当。
制剂实施例
1、1％2-氰基-3-氨基-3-苯基丙烯酸酯乙酯(氰烯菌酯)滴眼液和冲洗液
2-氰基-3-氨基-3-苯基丙烯酸酯乙酯(氰烯菌酯)1％(w/w)，吐温20 0.5％ (w/w)，甘露醇12.5％(w/w)，生理盐水补足100％，按常规方法制得10mg/ml 氰烯菌酯滴眼液和冲洗液。
2、10％(w/w)2-氰基-3-氨基-3-苯基丙烯酸酯甲酯即释片剂
2-氰基-3-氨基-3-苯基丙烯酸酯甲酯10％(w/w)，棕榈酰基肉碱62.1％(w/w)，山梨醇5％，甘露醇5.6％(w/w)，甘油单硬脂酸酯2.7％，硬脂酰富马酸钠0.6％ (w/w)，可压缩糖和淀粉10％，微晶纤维素4％，按常规方法制得17(w/w)氰烯菌酯即释片剂。
3、1.5％(w/w)2-氰基-3-氨基-3-苯基丙烯酸酯丙酯软膏剂
2-氰基-3-氨基-3-苯基丙烯酸酯丙酯1.5％(w/w)，十八醇7.8％(w/w)，苯甲酸钠2.6％(w/w)，无离子水6.5％(w/w)，水杨酸0.5％(w/w)，液状石蜡5.6％ (w/w)，凡士林5.0％(w/w)，单硬脂酸甘油酯55.5％(w/w)，十二烷基硫酸钠 15.0％(w/w)。
虽然已经结合其特定实施方案描述了本发明，应该理解，遵循本发明的一般性原理，本发明能够进行进一步修改并且本申请意欲覆盖本发明的任何变化、用途或改变，包括这样的在本发明所属领域已知的或常规的实践范围内的本公开内容的偏离，并可适用于上文阐述的必要特征，并在权利要求书的范围内遵循。
Claims (4)
1.氰基丙烯酸酯类化合物在制备用于治疗真菌引起的感染性人、畜疾病的药物中的应用，所述氰基丙烯酸酯类化合物是指以肌球蛋白为靶标的2-氰基-3-氨基-3-苯基丙烯酸酯甲酯、2-氰基-3-氨基-3-苯基丙烯酸酯乙酯、2-氰基-3-氨基-3-苯基丙烯酸酯丙酯，所述治疗真菌引起的感染性人、畜疾病是真菌引起的皮肤病。
2.根据权利要求1所述的应用，其特征在于所述氰基丙烯酸酯类化合物加工成固体、膏状和液体形态的制剂应用。
3.根据权利要求2所述的应用，其特征在于所述氰基丙烯酸酯类化合物加工成固体、膏状和液体形态的制剂是膏剂、片剂、胶囊、糖衣丸、粉末、颗粒、快速崩解型片剂、延迟释放剂、针剂、囊封或微囊封的制剂。
4.根据权利要求1-3任一所述的应用，其特征在于所述氰基丙烯酸酯类化合物是通过涂抹或冲洗患处、口服、注射方式给药。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710338081.XA CN106983741B (zh) | 2017-05-15 | 2017-05-15 | 氰基丙烯酸酯类化合物在制备治疗人畜真菌性感染疾病的药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710338081.XA CN106983741B (zh) | 2017-05-15 | 2017-05-15 | 氰基丙烯酸酯类化合物在制备治疗人畜真菌性感染疾病的药物中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106983741A CN106983741A (zh) | 2017-07-28 |
| CN106983741B true CN106983741B (zh) | 2019-08-20 |
Family
ID=59419364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710338081.XA Active CN106983741B (zh) | 2017-05-15 | 2017-05-15 | 氰基丙烯酸酯类化合物在制备治疗人畜真菌性感染疾病的药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106983741B (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110540995B (zh) * | 2018-05-28 | 2023-01-10 | 南京农业大学 | 一种降低肌球蛋白-5蛋白及其在氰基丙烯酸酯类药物抗性治理中的应用 |
| CN115177608B (zh) * | 2022-07-26 | 2023-12-05 | 南方医科大学南方医院 | 长链酰基肉碱类化合物在制备预防和/或治疗肝癌的药物中的应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1691940A (zh) * | 2001-01-16 | 2005-11-02 | 汉斯·布林克·利斯特 | 用于皮肤组织中出现的和/或损害皮肤组织的疾病预防性或治疗性治疗的氰基丙烯酸酯组合物 |
| CN101258850B (zh) * | 2008-04-18 | 2011-01-26 | 江苏中旗化工有限公司 | 2-氰基-3-氨基-3-苯基丙烯酸甲酯防治农作物病害的应用 |
| EP2892346B1 (en) * | 2012-09-07 | 2016-10-26 | Bayer CropScience AG | Active compound combinations |
-
2017
- 2017-05-15 CN CN201710338081.XA patent/CN106983741B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN106983741A (zh) | 2017-07-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO326139B1 (no) | Preparat omfattende et plantekjemikaliekonsentrat av Echinacea purpurea og benzalkoniumklorid. | |
| US9662360B2 (en) | Treatment of herpes, pseudomonas, staph, and hepatitis | |
| CN104367765A (zh) | 一种用于治疗抑郁症的中药组合物及其制备方法和应用 | |
| CN111568897A (zh) | 一种斑蝥素抗病毒、抗菌制剂、其制备方法及用作预防和治疗新冠病毒感染 | |
| CN106983741B (zh) | 氰基丙烯酸酯类化合物在制备治疗人畜真菌性感染疾病的药物中的应用 | |
| JP2005200339A (ja) | 抗菌剤 | |
| CN110664858B (zh) | 一种用于皮肤的青蒿提取物组合物、产品及其应用 | |
| CN105943666B (zh) | 一种用于婴幼儿敏感肌肤护理的组合物及其制备方法 | |
| CN108186639B (zh) | 一种盐酸奈康唑的药物组合物 | |
| CN106511478A (zh) | 一种治疗犬癣的复合精油及其制备方法和应用 | |
| CN106265713B (zh) | 虫草素在制备抗抑郁症的药物中的用途及其制备而得的快速抗抑郁症药物 | |
| CN106237029B (zh) | 一种芦荟抗菌凝胶及其制备方法 | |
| CN108785374A (zh) | 清香桂皮肤抑菌凝胶及其制备方法 | |
| CN108079050A (zh) | 本草皮肤抑菌组合物及其制备方法与应用 | |
| CN101766731B (zh) | 茶多酚抗痤疮外用制剂 | |
| CN103251636A (zh) | 一种治疗念珠菌感染及其所引起疾病的药物及其制备方法 | |
| CN111012740A (zh) | 恩康唑外用液体制剂及其制备方法 | |
| CN105326954A (zh) | 一种治疗睑缘炎的中药组合物及其制备方法 | |
| US20220047663A1 (en) | Formulation for inhibiting virus replication | |
| CN104116821A (zh) | 一种抗炎镇痛的药物组合物及其用途 | |
| AU2182699A (en) | Fungicide composition comprising a benzoylphenylurea | |
| CN109646435B (zh) | 厄他培南钠在制备防治牛传染性鼻气管炎药物中的应用 | |
| WO2021238836A1 (zh) | 一种斑蝥素抗病毒、抗菌制剂、其制备方法及用作预防和治疗新冠病毒感染 | |
| RU2375057C2 (ru) | Антигельминтный препарат для лечения мелкого рогатого скота | |
| CN101628026A (zh) | 治疗动物毛癣病的瑞香狼毒缓释注射剂及制备方法 |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |