JP2021134176A - Mucormycosis drug - Google Patents
Mucormycosis drug Download PDFInfo
- Publication number
- JP2021134176A JP2021134176A JP2020032263A JP2020032263A JP2021134176A JP 2021134176 A JP2021134176 A JP 2021134176A JP 2020032263 A JP2020032263 A JP 2020032263A JP 2020032263 A JP2020032263 A JP 2020032263A JP 2021134176 A JP2021134176 A JP 2021134176A
- Authority
- JP
- Japan
- Prior art keywords
- mucormycosis
- siccanin
- therapeutic agent
- drug
- amphotericin
- 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
- 206010061418 Zygomycosis Diseases 0.000 title claims abstract description 36
- 201000007524 mucormycosis Diseases 0.000 title claims abstract description 36
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 229940079593 drug Drugs 0.000 title claims description 4
- UGGAILYEBCSZIV-ITJSPEIASA-N Siccanin Chemical compound C1CCC(C)(C)[C@@H]2CC[C@]3(C)OC4=CC(C)=CC(O)=C4[C@H]4[C@@H]3[C@@]21CO4 UGGAILYEBCSZIV-ITJSPEIASA-N 0.000 claims abstract description 15
- UGGAILYEBCSZIV-UHFFFAOYSA-N Siccanin Natural products C1CCC(C)(C)C2CCC3(C)OC4=CC(C)=CC(O)=C4C4C3C21CO4 UGGAILYEBCSZIV-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229950008379 siccanin Drugs 0.000 claims abstract description 15
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 208000031888 Mycoses Diseases 0.000 claims description 5
- 241000235395 Mucor Species 0.000 claims description 4
- 206010017533 Fungal infection Diseases 0.000 claims description 3
- 241000235402 Rhizomucor Species 0.000 claims description 3
- 240000005384 Rhizopus oryzae Species 0.000 claims description 3
- 235000013752 Rhizopus oryzae Nutrition 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 abstract description 12
- 238000010586 diagram Methods 0.000 abstract 1
- 230000000844 anti-bacterial effect Effects 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 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 8
- 241000233866 Fungi Species 0.000 description 8
- 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 8
- 229960003942 amphotericin b Drugs 0.000 description 8
- 239000002502 liposome Substances 0.000 description 8
- -1 trichromazole Chemical compound 0.000 description 7
- 229940121375 antifungal agent Drugs 0.000 description 5
- 239000003429 antifungal agent Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 150000003904 phospholipids Chemical class 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 208000002474 Tinea Diseases 0.000 description 2
- 201000010618 Tinea cruris Diseases 0.000 description 2
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229930183167 cerebroside Natural products 0.000 description 2
- RIZIAUKTHDLMQX-UHFFFAOYSA-N cerebroside D Natural products CCCCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O RIZIAUKTHDLMQX-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 150000002339 glycosphingolipids Chemical class 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 1
- FROLUYNBHPUZQU-IIZJPUEISA-N (2R,3R,4S,5R)-2-(hydroxymethyl)-6-[3-[3-[(3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypropoxy]propoxy]oxane-3,4,5-triol Chemical compound OC[C@H]1OC(OCCCOCCCOC2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@H]1O FROLUYNBHPUZQU-IIZJPUEISA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 1
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- LVNGJLRDBYCPGB-UHFFFAOYSA-N 1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-UHFFFAOYSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- IIUZTXTZRGLYTI-UHFFFAOYSA-N Dihydrogriseofulvin Natural products COC1CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 IIUZTXTZRGLYTI-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000005373 Dyshidrotic Eczema Diseases 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- UXWOXTQWVMFRSE-UHFFFAOYSA-N Griseoviridin Natural products O=C1OC(C)CC=C(C(NCC=CC=CC(O)CC(O)C2)=O)SCC1NC(=O)C1=COC2=N1 UXWOXTQWVMFRSE-UHFFFAOYSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010065973 Iron Overload Diseases 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 1
- DDUHZTYCFQRHIY-UHFFFAOYSA-N Negwer: 6874 Natural products COC1=CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-UHFFFAOYSA-N 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000992410 Pyrenophora lolii Species 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000130764 Tinea Species 0.000 description 1
- 241000893966 Trichophyton verrucosum Species 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229960000958 deferoxamine Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 208000013046 dyshidrosis Diseases 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- DDUHZTYCFQRHIY-RBHXEPJQSA-N griseofulvin Chemical compound COC1=CC(=O)C[C@@H](C)[C@@]11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-RBHXEPJQSA-N 0.000 description 1
- 229960002867 griseofulvin Drugs 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960003255 natamycin Drugs 0.000 description 1
- NCXMLFZGDNKEPB-FFPOYIOWSA-N natamycin 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@@H](C)OC(=O)/C=C/[C@H]2O[C@@H]2C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 NCXMLFZGDNKEPB-FFPOYIOWSA-N 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 229960000988 nystatin Drugs 0.000 description 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 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/CC/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)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 210000003254 palate Anatomy 0.000 description 1
- 210000003695 paranasal sinus Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 201000011414 pompholyx Diseases 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000036555 skin type Effects 0.000 description 1
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 238000011179 visual inspection Methods 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
【課題】新たなムーコル症治療薬の提供。【解決手段】シッカニンを有効成分とするムーコル症治療薬。【選択図】なしPROBLEM TO BE SOLVED: To provide a new therapeutic agent for mucormycosis. SOLUTION: A therapeutic agent for mucormycosis containing siccanin as an active ingredient. [Selection diagram] None
Description
本発明は、ムーコル症治療薬に関する。 The present invention relates to a therapeutic agent for mucormycosis.
ムーコル症は、ムーコル目の真菌による感染症の総称であり、日和見型深在性真菌症の一つである。従って、発症には、宿主要因が強く関係し、重篤な免疫不全の存在下で発症する。危険因子としては、長期間の好中球減少、ステロイド投与、リンパ球減少、骨髄移植、コントロール不能の糖尿病などがある。輸血後の鉄過剰に対する除鉄剤であるデフェロキサミンの投与中にも発症しやすい。新規アゾール系薬であるボリコナゾール投与中のブレークスルー感染症としての報告も増えている。
感染経路としては、環境中に浮遊する真菌を吸い込むことによる経気道感染が主な経路と考えられている。また、消化管からの感染経路も推測されている。最も多い病型は、鼻脳型で、副鼻腔から感染が始まり、眼窩や口蓋を巻き込み、脳へと波及する。その他、肺型、皮膚型、消化管型がある。急性に進行し、最も予後不良な真菌症であり、大多数は致死的転機をたどる。
Mucormycosis is a general term for infectious diseases caused by fungi of the order Mucormycosis, and is one of opportunistic deep-seated fungal diseases. Therefore, host factors are strongly associated with the onset and develop in the presence of severe immunodeficiency. Risk factors include long-term neutropenia, steroid administration, lymphopenia, bone marrow transplantation, and uncontrolled diabetes. It is also likely to develop during administration of deferoxamine, an iron-removing agent for iron overload after blood transfusion. There are increasing reports of breakthrough infections during administration of the novel azole drug voriconazole.
The main route of infection is considered to be trans-respiratory tract infection by inhaling fungi floating in the environment. The route of infection from the digestive tract is also speculated. The most common type is the nasal brain type, in which infection begins in the paranasal sinuses, involves the orbit and palate, and spreads to the brain. In addition, there are lung type, skin type, and gastrointestinal type. It progresses acutely and has the poorest prognosis, with the majority following a fatal turning point.
特徴的な臨床症状がなく、血清診断もないため、確定診断には、病理組織学的検査、真菌学的検査が必要である。最も強力な抗真菌薬であるアゾール系抗真菌薬やキャンディン系抗真菌薬は無効であり、臨床的には唯一アムホテリシンＢのみが有効とされている。 Since there are no characteristic clinical symptoms and no serodiagnosis, histopathological examination and mycological examination are required for definitive diagnosis. The most potent antifungal agents, azole antifungal agents and candin antifungal agents, are ineffective, and only amphotericin B is clinically effective.
皮膚ムーコル菌症の原因菌とされる真菌に関しては、いくつかの抗真菌薬についてＩＦＯに寄託されている基準菌株を用いて抗菌作用が検討されている（非特許文献１）。この非特許文献１によれば、アムホテリシンＢ、トリクロマゾール、メルゾニンは、皮膚ムーコル症原因真菌に対して抗菌作用を示したが、ナフチオメート、グリセオフルビン、シッカニン、５−ＦＣ、ナイスタチン、ピマフシンは、有効でなかったことが記載されている。 Regarding the fungus that is considered to be the causative agent of cutaneous Mucor fungus, antibacterial activity has been investigated using a reference strain deposited with IFO for some antifungal agents (Non-Patent Document 1). According to this Non-Patent Document 1, amphotericin B, trichromazole, and merzonin showed antibacterial activity against skin mucormycosis-causing fungi, but naphthomate, griseofulvin, siccanin, 5-FC, nystatin, and pimafucin are effective. It is stated that it was not.
しかしながら、日本でムーコル症治療薬として認められているのは、アムホテリシンＢのみであり、臨床的に有効で、安全性の高いムーコル症治療薬が望まれていた。
従って、本発明の課題は、臨床的に有効で、安全性の高いムーコル症治療薬を提供することにある
However, amphotericin B is the only drug approved as a therapeutic agent for mucormycosis in Japan, and a clinically effective and highly safe therapeutic agent for mucormycosis has been desired.
Therefore, an object of the present invention is to provide a clinically effective and highly safe therapeutic agent for mucormycosis.
そこで本発明者は、寄託機関が保有している基準菌株ではなく、ムーコル症の臨床分離株を用いて種々の成分について、抗真菌作用を検討したところ、古くから抗真菌薬として用いられているが、ムーコル症に有効とされていないシッカニンが、現在唯一有効とされているアムホテリシンＢよりも優れたムーコル症原因真菌に対する抗菌作用を示し、かつヒトの細胞に対する毒性は弱いことを見出し、本発明を完成した。 Therefore, the present inventor examined the antifungal action of various components using a clinical isolate of mucormycosis instead of the reference strain owned by the depositary institution, and found that it has been used as an antifungal agent for a long time. However, it was found that zygomycosis, which is not effective for mucormycosis, exhibits a superior antifungal action against mucormycosis-causing fungi and is less toxic to human cells than amphotericin B, which is currently considered to be the only effective agent. Was completed.
すなわち、本発明は、次の発明［１］〜［２］を提供するものである。
［１］シッカニンを有効成分とするムーコル症治療薬。
［２］ムーコル症が、Ｒｈｉｚｏｐｕｓ ｏｒｙｚａｅ、Ｃｕｎｎｉｎｇｈｍｅｌｌａ ｂｅｒｔｈｏｌｌｅｔｉａｅ、Ｌｃｈｔｈｅｉｍｉａ ｒａｍｏｓａ、Ｒｈｉｚｏｍｕｃｏｒ ｐｕｓｉｌｌｕｓ及びＭｕｃｏｒ ｃｉｒｃｉｎｅｌｌｏｉｄｅｓから選ばれる真菌の感染によるムーコル症である［１］記載のムーコル症治療薬。
That is, the present invention provides the following inventions [1] to [2].
[1] A therapeutic agent for mucormycosis containing siccanin as an active ingredient.
[2] Mucormycosis is a mucormycosis caused by a fungal infection selected from Rhizopus oryzae, Cunninghmella bertholletiae, Lchtheimia ramosa, Rhizomucor pusilulus and Mucor cyrcinelloides.
本発明によれば、ムーコル症原因真菌に対して強い抗菌作用を示し、安全性の高いムーコル症治療薬が提供できる。 According to the present invention, it is possible to provide a highly safe therapeutic agent for mucormycosis, which exhibits a strong antibacterial action against the fungus causing mucormycosis.
本発明のムーコル症治療薬の有効成分は、シッカニンである。
シッカニンは、Ｈｅｌｍｉｎｔｈｏｓｐｏｒｉｕｍ ｓｉｃｃａｎｓ Ｄｒｅｃｈｓｌｅｒ培養濾液より分離された抗生物質で、次の構造を有する。
The active ingredient of the therapeutic agent for mucormycosis of the present invention is siccanin.
Siccanin is an antibiotic isolated from the Helminthosporium siccans Drechsler culture filtrate and has the following structure.
シッカニンは、猩紅色菌、趾間菌、星芒状菌に対して強い抗菌作用を有し、汗疱状白癬、頑癬、斑状小水疱性白癬の治療薬として、外用薬の形態で販売されている。 Siccanin has a strong antibacterial effect against ringworm, interdigital bacteria, and tinea cruris, and is marketed as an external preparation for the treatment of dyshidrosis, tinea cruris, and vesicular vesicular tinea. ..
しかし、非特許文献１のように、ＩＦＯに寄託されているほとんどのムーコル症原因菌基準株に対しては抗菌作用を示さないと報告されている。
これに対し、ムーコル症の臨床分離株を用いた抗菌試験で、シッカニンは、アムホテリシンＢよりも強い抗菌作用を示した。また、シッカニンは、ヒト培養細胞に対しては、アムホテリシンＢよりも低い細胞毒性を示した。
従って、シッカニンは、ムーコル症治療薬として有用である。
However, as in Non-Patent Document 1, it is reported that it does not show antibacterial activity against most of the mucormycosis-causing strains deposited in IFO.
In contrast, in antibacterial studies using clinical isolates of mucormycosis, siccanin showed stronger antibacterial activity than amphotericin B. In addition, siccanin showed lower cytotoxicity to cultured human cells than amphotericin B.
Therefore, cycanin is useful as a therapeutic agent for mucormycosis.
また、シッカニンは、特にＲｈｉｚｏｐｕｓ ｏｒｙｚａｅ、Ｃｕｎｎｉｎｇｈｍｅｌｌａ ｂｅｒｔｈｏｌｌｅｔｉａｅ、Ｌｃｈｔｈｅｉｍｉａ ｒａｍｏｓａ、Ｒｈｉｚｏｍｕｃｏｒ ｐｕｓｉｌｌｕｓ及びＭｕｃｏｒ ｃｉｒｃｉｎｅｌｌｏｉｄｅｓから選ばれる真菌の感染によるムーコル症治療薬として有用である。 Mucormycosis is also a mucormycosis due to fungal infections, especially selected from Rhizopus oryzae, Cunninghmella bertholletiae, Lchtheimia ramosa, Rhizomucor fungalus and Mucor cyrcinelloides.
シッカニンは、常法により錠剤、顆粒剤、散剤、カプセル剤、懸濁剤、注射剤、坐剤、外用剤等の種々の剤型のムーコル症治療用医薬組成物とすることができる。これらの医薬組成物は、シッカニンに薬学的に許容される担体を配合して製造することができる。使用できる薬学的に許容される担体としては、例えば、経口製剤や注射剤であれば、賦形剤、結合剤、被覆剤、滑沢剤、糖衣剤、崩壊剤、増量剤、矯味矯臭剤、乳化・可溶化・分散剤、安定剤、ｐＨ調整剤、等張剤等が例示できる。皮膚外用剤や膣座剤であれば、ワセリンやマイクロクリスタリンワックス等のような炭化水素類、ホホバ油やゲイロウ等のエステル類、牛脂、オリーブ油等のトリグリセライド類、セタノール、オレイルアルコール等の高級アルコール類、ステアリン酸、オレイン酸等の脂肪酸、グリセリンや１，３−ブタンジオール等の多価アルコール類、非イオン界面活性剤、アニオン界面活性剤、カチオン界面活性剤、両性界面活性剤、エタノール、カーボポール等の増粘剤、防腐剤、紫外線吸収剤、抗酸化剤、色素、粉体類等が例示できる。注射剤の場合には、シッカニンを注射用蒸留水等の水性担体にあらかじめ溶解、分散、乳化等して注射用液剤とするか、または注射用粉末にして用時に溶解等すればよい。注射剤の投与方法としては静脈内投与、動脈内投与、皮下投与、静注点滴が挙げられる。
ムーコル症は、前記のごとく日和見型深在性真菌症であることから、本発明の医薬は、外用剤として使用してもよいが、経口投与用組成物又は注射用組成物とするのがより好ましい。
Sikkanin can be used as a pharmaceutical composition for treating mucormycosis in various dosage forms such as tablets, granules, powders, capsules, suspensions, injections, suppositories, and external preparations by a conventional method. These pharmaceutical compositions can be produced by blending siccanin with a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers that can be used include, for example, excipients, binders, coatings, lubricants, sugar coatings, disintegrants, bulking agents, flavoring agents, in the case of oral preparations and injections. Examples thereof include emulsifying / solubilizing / dispersing agents, stabilizers, pH adjusting agents, isotonic agents and the like. For skin external preparations and vaginal suppositories, hydrocarbons such as vaseline and microcrystallin wax, esters such as jojoba oil and gay wax, triglycerides such as beef fat and olive oil, and higher alcohols such as cetanol and oleyl alcohol. , Stearic acid, fatty acids such as oleic acid, polyhydric alcohols such as glycerin and 1,3-butanediol, nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, ethanol, carbopole Such as thickeners, preservatives, ultraviolet absorbers, antioxidants, pigments, powders and the like can be exemplified. In the case of an injection, siccanin may be previously dissolved, dispersed, emulsified or the like in an aqueous carrier such as distilled water for injection to prepare an injection liquid, or it may be made into an injection powder and dissolved at the time of use. Examples of the method for administering the injection include intravenous administration, intraarterial administration, subcutaneous administration, and intravenous drip infusion.
Since mucormycosis is an opportunistic deep-seated fungal disease as described above, the medicament of the present invention may be used as an external preparation, but it is more preferable to use a composition for oral administration or a composition for injection. preferable.
また、シッカニンをリポソーム中に組み込んだリポソーム製剤とすることにより、静脈内投与後に高い血中濃度を維持し、感染組織への移行を良好にし、正常組織への移行を低減させることもできる。ここで、シッカニン含有リポソーム製剤は、種々の脂質類、コレステロールなどで形成されるリポソームの膜中またはリポソーム内にシッカニンを保持させることにより得られる。
用いられる脂質類としては、リン脂質、グリセロ糖脂質、スフィンゴ糖脂質などが挙げられる。
リン脂質としては、例えばホスファチジルコリン（大豆ホスファチジルコリン、卵黄ホスファチジルコリン、ジステアロイルホスファチジルコリン、ジパルミトイルホスファチジルコリン等）、ホスファチジルエタノールアミン（ジステアロイルホスファチジルエタノールアミン等）、ホスファチジルセリン、ホスファチジン酸、ホスファチジルグリセロール、ホスファチジルイノシトール、リゾホスファチジルコリン、スフィンゴミエリン、卵黄レシチン、大豆レシチン、水素添加リン脂質等の天然又は合成のリン脂質等が挙げられる。
グリセロ糖脂質としては、例えばスルホキシリボシルグリセリド、ジグリコシルジグリセリド、ジガラクトシルジグリセリド、ガラクトシルジグリセリド、グリコシルジグリセリド等が挙げられる。スフィンゴ糖脂質としては、例えばガラクトシルセレブロシド、ラクトシルセレブロシド、ガングリオシド等が挙げられる。
また必要に応じて膜安定化剤としてコレステロール類、抗酸化剤としてトコフェロール類、ステアリルアミン、ジセチルホスフェート、ガレグリオシドを用いてもよい。
リポソームの製造には、公知のリポソームの調製法を適用することができ、例えばバンガム（Bangham）らのリポソーム調製法［ジャーナル・オブ・モレキュラー・バイオロジー(J. Mol. Biol.), 13, 238(1965)］、エタノール注入法［ジャーナル・オブ・セル・バイオロジー(J. Cell. Biol.), 66, 621(1975)］、フレンチプレス法［フェブス・レター(FEBS Lett.), 99, 210(1979)］、凍結融解法［アーカイブス・オブ・バイオケミストリー・アンド・バイオフィジックス(Arch. Biochem. Biophys.), 212, 186(1981)］、逆相蒸発法［プロシーディング・オブ・ザ・ナショナル・アカデミー・オブ・サイエンシズ・ユー・エス・エー(Proc. Natl. Acad. Sci. USA), 75, 4194(1978)］等が挙げられる。例えば、脂質類等を有機溶媒に溶解し、これに水性溶液を加え、次いで、超音波処理してリポソーム懸濁液を得る。次いで必要によりこれをエクストルーダー及び／又はメンブランフィルターを用いて、整粒する。このとき、粒子径は、１μm以下、さらに１００〜８００nm、特に１００〜６００nmに整粒するのが好ましい。
In addition, by preparing a liposome preparation in which siccanin is incorporated into liposomes, it is possible to maintain a high blood concentration after intravenous administration, improve the transfer to infected tissues, and reduce the transfer to normal tissues. Here, the siccanin-containing liposome preparation is obtained by retaining siccanin in or in the membrane of a liposome formed of various lipids, cholesterol and the like.
Examples of the lipids used include phospholipids, glyceroglycolipids, glycosphingolipids and the like.
Examples of phospholipids include phosphatidylcholine (soy phosphatidylcholine, egg yolk phosphatidylcholine, distearoylphosphatidylcholine, dipalmitoylphosphatidylcholine, etc.), phosphatidylethanolamine (distearoylphosphatidylethanolamine, etc.), phosphatidylserine, phosphatidylphosphate, phosphatidylglycerol, phosphatidylglycerol , Natural or synthetic phospholipids such as sphingomierin, egg yolk lecithin, soy lecithin, hydrogenated phospholipids and the like.
Examples of glyceroglycolipids include sulfoxyribosylglyceride, diglycosyldiglyceride, digalactosyldiglyceride, galactosyldiglyceride, glycosyldiglyceride and the like. Examples of glycosphingolipids include galactosyl cerebroside, lactosyl cerebroside, and ganglioside.
If necessary, cholesterols may be used as the membrane stabilizer, and tocopherols, stearylamine, disetylphosphate, and galeglioside may be used as the antioxidant.
Known liposome preparation methods can be applied to the production of liposomes, for example, the liposome preparation method of Bangham et al. [Journal of Molecular Biology (J. Mol. Biol.), 13, 238. (1965)], Ethanol injection method [Journal of Cell. Biol., 66, 621 (1975)], French press method [FEBS Lett., 99, 210 (1979)], freeze-thaw method [Arch. Biochem. Biophys., 212, 186 (1981)], reverse phase evaporation method [Proceeding of the National]・ Academy of Sciences USA (Proc. Natl. Acad. Sci. USA), 75, 4194 (1978)]. For example, lipids and the like are dissolved in an organic solvent, an aqueous solution is added thereto, and then ultrasonic treatment is performed to obtain a liposome suspension. Then, if necessary, this is sized using an extruder and / or a membrane filter. At this time, the particle size is preferably 1 μm or less, and more preferably 100 to 800 nm, particularly 100 to 600 nm.
シッカニンをムーコル症治療薬として用いる場合の投与量は、疾患、症状、体重、年齢、性別、投与経路等の種々の要因によって異なるが、シッカニン換算で通常成人に対しては、好ましくは０．１〜１０００ｍｇ／日、より好ましくは１〜３００ｍｇ／日が用いられる。また、この量を１日１回でまたは２〜４回に分割して投与してもよい。 The dose of zygomycosis used as a therapeutic agent for mucormycosis varies depending on various factors such as disease, symptom, body weight, age, sex, route of administration, etc., but is usually 0.1 for adults in terms of zygomycosis. ~ 1000 mg / day, more preferably 1-300 mg / day is used. Moreover, this amount may be administered once a day or divided into 2 to 4 times.
以下、実施例を挙げて本発明を更に詳細に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
実施例１
臨床分離株をＰＤＡ斜向培地で株起こし、３７℃で培養した。次に、ＤＷで胞子を回収し、菌数を調整した。９６穴プレートにＲＰＭＩ培地を菌液と合わせて１０３個/１００μＬ／ウェルアプライし、菌株により３５℃で本培養した。この時、被検成分もアプライした。菌の増殖状態を写真、目視及びスキャナーで測定した。
ヒト肝臓由来培養細胞（ＨｕＨ−7）を用いた細胞毒性は、前培養でＨｕＨ−7細胞を調整し、本培養は96穴プレートにＤＭＥＭ（ＦＢＳ１０％）を１００μＬ/ｗｅｌｌ使用し、３７℃（５％ ＣＯ２）で一晩培養後、ＷＳＴ−１試薬を添加して、Ｏ.Ｄ.４９０ｎｍの測定により毒性を判定した。
結果を、表１に示す。
Example 1
The clinical isolate was raised in PDA oblique medium and cultured at 37 ° C. Next, spores were collected by DW and the number of bacteria was adjusted. RPMI medium was combined with the bacterial solution on a 96-well plate, 10 3 cells / 100 μL / well applied, and the cells were main-cultured at 35 ° C. At this time, the test component was also applied. The growth state of the bacterium was measured by photography, visual inspection and scanner.
For cytotoxicity using cultured human liver-derived cells (HuH-7), HuH-7 cells were prepared in the preculture, and 100 μL / well of DMEM (FBS 10%) was used in the 96-well plate in the main culture at 37 ° C. ( After culturing overnight at 5% CO 2 ), WST-1 reagent was added, and toxicity was determined by measuring OD 490 nm.
The results are shown in Table 1.
表１より、シッカニンは、ムーコル症原因真菌の臨床分離株に対して優れた抗菌作用を示すことがわかる。その抗菌作用は、ムーコル症治療薬として認められているアムホテリシンＢよりも強いことがわかる。さらに、シッカニンは、ヒト培養細胞に対する毒性はアムホテリシンＢよりも低かった。 From Table 1, it can be seen that zygomycosis exhibits excellent antibacterial activity against clinical isolates of mucormycosis-causing fungi. It can be seen that its antibacterial activity is stronger than that of amphotericin B, which is approved as a therapeutic agent for mucormycosis. In addition, siccanin was less toxic to cultured human cells than amphotericin B.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2020032263A JP2021134176A (en) | 2020-02-27 | 2020-02-27 | Mucormycosis drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2020032263A JP2021134176A (en) | 2020-02-27 | 2020-02-27 | Mucormycosis drug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2021134176A true JP2021134176A (en) | 2021-09-13 |
Family
ID=77660267
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020032263A Pending JP2021134176A (en) | 2020-02-27 | 2020-02-27 | Mucormycosis drug |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2021134176A (en) |
-
2020
- 2020-02-27 JP JP2020032263A patent/JP2021134176A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zarif et al. | Cochleates: new lipid-based drug delivery system | |
| ES2363019T3 (en) | USE OF PIRLINDOL FOR THE TREATMENT OF DISEASES THAT ARE CHARACTERIZED BY A PROLIFERATION OF T-LYMPHOCYTES AND / OR HYPERPROLIFERATION OF KERATINOCITS IN PARTICULATE AOPHIC DERMATITIS AND PSORIASIS. | |
| RU2659729C2 (en) | Cohleates made with soy phosphatidylserine | |
| CN106535907A (en) | Composition for treating or preventing metabolic disease, containing, as active ingredient, extracellular vesicles derived from akkermansia muciniphila bacteria | |
| JP2017226691A (en) | Novel formulations of volatile anesthetics and methods of use thereof for reducing inflammation | |
| CN103083239A (en) | Bufalin lipidosome, preparation method and application thereof | |
| CN108495619A (en) | Echinomycin preparation and preparation method thereof and application method | |
| WO2015172712A1 (en) | Pharmaceutical composition for injection with synergistic effect of vitamin c and antitumour drugs | |
| WO2021196659A1 (en) | Glycosyl polyether compound liposome, preparation method therefor and medicine thereof | |
| CN111346081B (en) | Novel use of a pharmaceutical composition comprising n-valeric acid, indole propionic acid and sodium n-butyrate | |
| AU2008331500B2 (en) | Intravesical compositions with valrubicin for the treatment of bladder cancer | |
| WO2013176223A1 (en) | Pharmaceutical composition for treating inflammatory disease | |
| JP2014122244A (en) | Novel formulation for treating fungal infections | |
| JPH07501825A (en) | Amphotericin B composition with enhanced antifungal activity | |
| US20240074974A1 (en) | Methods and related compositions for the treatment of cancer | |
| CA2671668A1 (en) | Therapeutic composition for interstitial pheumonia | |
| JP2021134176A (en) | Mucormycosis drug | |
| JPH01233219A (en) | Carcinostatic agent composition | |
| CN115804755B (en) | Docetaxel liposome composition and preparation method thereof | |
| KR20110094321A (en) | Inhalants containing modified superoxide dismutase | |
| Smith et al. | LIPID PRODRUG NANOPARTICLES CARRYING A MIMETIC PEPTIDE OF APOLIPOPROTEIN A-II TARGET PANCREATIC ADENOCARCINOMA | |
| EA013570B1 (en) | Pharmaceutical composition for treating tuberculosis and diseases mediated by helicobacter pylori based on solid lipid nanoparticles and a method for the treatment of tuberculosis | |
| CN116102633A (en) | Antibacterial shampoo | |
| CN119909018A (en) | A long-acting fulvestrant liposome for injection and a preparation method thereof | |
| CN118680882A (en) | Application of drug-loaded lipid nanocarriers in the preparation of drugs for the treatment of drug-resistant lung cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20210311 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20210311 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210817 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211007 |