JP6086539B2 - 非経口投与のためのアゾール医薬製剤ならびにその調製方法およびアゾール化合物に対して感受性の疾患の処置としてのその使用方法 - Google Patents
非経口投与のためのアゾール医薬製剤ならびにその調製方法およびアゾール化合物に対して感受性の疾患の処置としてのその使用方法 Download PDFInfo
- Publication number
- JP6086539B2 JP6086539B2 JP2013544816A JP2013544816A JP6086539B2 JP 6086539 B2 JP6086539 B2 JP 6086539B2 JP 2013544816 A JP2013544816 A JP 2013544816A JP 2013544816 A JP2013544816 A JP 2013544816A JP 6086539 B2 JP6086539 B2 JP 6086539B2
- Authority
- JP
- Japan
- Prior art keywords
- composition
- solvent
- itza
- peg
- azole
- 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.)
- Expired - Fee Related
Links
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title claims description 132
- 238000000034 method Methods 0.000 title claims description 49
- 238000011282 treatment Methods 0.000 title claims description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 17
- 238000002360 preparation method Methods 0.000 title claims description 17
- 201000010099 disease Diseases 0.000 title claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 150000003851 azoles Chemical class 0.000 title description 24
- 238000007911 parenteral administration Methods 0.000 title description 15
- 239000000203 mixture Substances 0.000 claims description 224
- 239000002904 solvent Substances 0.000 claims description 214
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 158
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 126
- 239000003814 drug Substances 0.000 claims description 123
- RAGOYPUPXAKGKH-XAKZXMRKSA-N posaconazole Chemical group O=C1N([C@H]([C@H](C)O)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3C[C@@](CN4N=CN=C4)(OC3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 RAGOYPUPXAKGKH-XAKZXMRKSA-N 0.000 claims description 85
- 229960001589 posaconazole Drugs 0.000 claims description 84
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 42
- 229960004130 itraconazole Drugs 0.000 claims description 42
- 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 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
- 229920001223 polyethylene glycol Polymers 0.000 claims description 39
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 37
- 239000002202 Polyethylene glycol Substances 0.000 claims description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 34
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 33
- 238000001802 infusion Methods 0.000 claims description 32
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 31
- 229940121375 antifungal agent Drugs 0.000 claims description 29
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 27
- 239000008121 dextrose Substances 0.000 claims description 27
- 239000011780 sodium chloride Substances 0.000 claims description 27
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- 208000031888 Mycoses Diseases 0.000 claims description 22
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 22
- 239000003978 infusion fluid Substances 0.000 claims description 18
- 239000003429 antifungal agent Substances 0.000 claims description 17
- 238000010790 dilution Methods 0.000 claims description 16
- 239000012895 dilution Substances 0.000 claims description 16
- 230000002538 fungal effect Effects 0.000 claims description 15
- -1 polyethylene Polymers 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 239000002736 nonionic surfactant Substances 0.000 claims description 11
- 150000002632 lipids Chemical class 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 239000000839 emulsion Substances 0.000 claims description 7
- 229960004884 fluconazole Drugs 0.000 claims description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 6
- 229960004125 ketoconazole Drugs 0.000 claims description 6
- 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 claims description 5
- 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 claims description 5
- 201000007524 mucormycosis Diseases 0.000 claims description 5
- 201000002909 Aspergillosis Diseases 0.000 claims description 4
- 208000036641 Aspergillus infections Diseases 0.000 claims description 4
- 206010007134 Candida infections Diseases 0.000 claims description 4
- 201000003984 candidiasis Diseases 0.000 claims description 4
- 238000007865 diluting Methods 0.000 claims description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 4
- 150000003852 triazoles Chemical class 0.000 claims description 4
- 229960004740 voriconazole Drugs 0.000 claims 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 claims description 4
- BLSQLHNBWJLIBQ-OZXSUGGESA-N (2R,4S)-terconazole Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2N=CN=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 BLSQLHNBWJLIBQ-OZXSUGGESA-N 0.000 claims description 3
- AFNXATANNDIXLG-SFHVURJKSA-N 1-[(2r)-2-[(4-chlorophenyl)methylsulfanyl]-2-(2,4-dichlorophenyl)ethyl]imidazole Chemical compound C1=CC(Cl)=CC=C1CS[C@H](C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 AFNXATANNDIXLG-SFHVURJKSA-N 0.000 claims description 3
- ZCJYUTQZBAIHBS-UHFFFAOYSA-N 1-[2-(2,4-dichlorophenyl)-2-{[4-(phenylsulfanyl)benzyl]oxy}ethyl]imidazole Chemical compound ClC1=CC(Cl)=CC=C1C(OCC=1C=CC(SC=2C=CC=CC=2)=CC=1)CN1C=NC=C1 ZCJYUTQZBAIHBS-UHFFFAOYSA-N 0.000 claims description 3
- OCAPBUJLXMYKEJ-UHFFFAOYSA-N 1-[biphenyl-4-yl(phenyl)methyl]imidazole Chemical compound C1=NC=CN1C(C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 OCAPBUJLXMYKEJ-UHFFFAOYSA-N 0.000 claims description 3
- JLGKQTAYUIMGRK-UHFFFAOYSA-N 1-{2-[(7-chloro-1-benzothiophen-3-yl)methoxy]-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound ClC1=CC(Cl)=CC=C1C(OCC=1C2=CC=CC(Cl)=C2SC=1)CN1C=NC=C1 JLGKQTAYUIMGRK-UHFFFAOYSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 3
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical group ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 claims description 3
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 claims description 3
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 claims description 3
- 229920002593 Polyethylene Glycol 800 Polymers 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- TYBHXIFFPVFXQW-UHFFFAOYSA-N abafungin Chemical compound CC1=CC(C)=CC=C1OC1=CC=CC=C1C1=CSC(NC=2NCCCN=2)=N1 TYBHXIFFPVFXQW-UHFFFAOYSA-N 0.000 claims description 3
- 229950006373 abafungin Drugs 0.000 claims description 3
- 229960002206 bifonazole Drugs 0.000 claims description 3
- 229960004022 clotrimazole Drugs 0.000 claims description 3
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 claims description 3
- 229960001274 fenticonazole Drugs 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 229960002509 miconazole Drugs 0.000 claims description 3
- 229960004031 omoconazole Drugs 0.000 claims description 3
- JMFOSJNGKJCTMJ-ZHZULCJRSA-N omoconazole Chemical compound C1=CN=CN1C(/C)=C(C=1C(=CC(Cl)=CC=1)Cl)\OCCOC1=CC=C(Cl)C=C1 JMFOSJNGKJCTMJ-ZHZULCJRSA-N 0.000 claims description 3
- 229960003483 oxiconazole Drugs 0.000 claims description 3
- QRJJEGAJXVEBNE-MOHJPFBDSA-N oxiconazole Chemical compound ClC1=CC(Cl)=CC=C1CO\N=C(C=1C(=CC(Cl)=CC=1)Cl)\CN1C=NC=C1 QRJJEGAJXVEBNE-MOHJPFBDSA-N 0.000 claims description 3
- 229960005429 sertaconazole Drugs 0.000 claims description 3
- 229960002607 sulconazole Drugs 0.000 claims description 3
- 229960000580 terconazole Drugs 0.000 claims description 3
- LEZWWPYKPKIXLL-UHFFFAOYSA-N 1-{2-(4-chlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound C1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 LEZWWPYKPKIXLL-UHFFFAOYSA-N 0.000 claims description 2
- 229960003913 econazole Drugs 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 2
- MPIPASJGOJYODL-SFHVURJKSA-N (R)-isoconazole Chemical compound ClC1=CC(Cl)=CC=C1[C@@H](OCC=1C(=CC=CC=1Cl)Cl)CN1C=NC=C1 MPIPASJGOJYODL-SFHVURJKSA-N 0.000 claims 1
- 239000004698 Polyethylene Substances 0.000 claims 1
- 229960005074 butoconazole Drugs 0.000 claims 1
- SWLMUYACZKCSHZ-UHFFFAOYSA-N butoconazole Chemical compound C1=CC(Cl)=CC=C1CCC(SC=1C(=CC=CC=1Cl)Cl)CN1C=NC=C1 SWLMUYACZKCSHZ-UHFFFAOYSA-N 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 229960004849 isoconazole Drugs 0.000 claims 1
- 229920000573 polyethylene Polymers 0.000 claims 1
- 229940079593 drug Drugs 0.000 description 117
- 238000009472 formulation Methods 0.000 description 105
- 239000003981 vehicle Substances 0.000 description 83
- 210000002381 plasma Anatomy 0.000 description 48
- 239000003085 diluting agent Substances 0.000 description 38
- 238000004128 high performance liquid chromatography Methods 0.000 description 34
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000000523 sample Substances 0.000 description 28
- 208000015181 infectious disease Diseases 0.000 description 27
- 238000002474 experimental method Methods 0.000 description 23
- 238000002347 injection Methods 0.000 description 23
- 239000007924 injection Substances 0.000 description 23
- 230000009885 systemic effect Effects 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 19
- 230000000843 anti-fungal effect Effects 0.000 description 19
- 241000282412 Homo Species 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 18
- 239000013543 active substance Substances 0.000 description 18
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 206010017533 Fungal infection Diseases 0.000 description 16
- 230000036470 plasma concentration Effects 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 241000233866 Fungi Species 0.000 description 14
- 238000010268 HPLC based assay Methods 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 14
- 239000008280 blood Substances 0.000 description 14
- 238000000338 in vitro Methods 0.000 description 13
- 230000031891 intestinal absorption Effects 0.000 description 13
- 230000014759 maintenance of location Effects 0.000 description 13
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 12
- 241000124008 Mammalia Species 0.000 description 11
- 229960000583 acetic acid Drugs 0.000 description 11
- 239000002131 composite material Substances 0.000 description 11
- 238000000605 extraction Methods 0.000 description 11
- 230000007774 longterm Effects 0.000 description 11
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 10
- 239000003643 water by type Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 206010061598 Immunodeficiency Diseases 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 238000001647 drug administration Methods 0.000 description 9
- 230000002949 hemolytic effect Effects 0.000 description 9
- 244000144972 livestock Species 0.000 description 9
- 231100000252 nontoxic Toxicity 0.000 description 9
- 230000003000 nontoxic effect Effects 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000002960 lipid emulsion Substances 0.000 description 8
- 210000004185 liver Anatomy 0.000 description 8
- 102000004506 Blood Proteins Human genes 0.000 description 7
- 108010017384 Blood Proteins Proteins 0.000 description 7
- 230000002924 anti-infective effect Effects 0.000 description 7
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 239000008177 pharmaceutical agent Substances 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 206010018910 Haemolysis Diseases 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 230000008030 elimination Effects 0.000 description 5
- 238000003379 elimination reaction Methods 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 230000008588 hemolysis Effects 0.000 description 5
- 230000000968 intestinal effect Effects 0.000 description 5
- 229940126701 oral medication Drugs 0.000 description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- 238000005063 solubilization Methods 0.000 description 5
- 230000007928 solubilization Effects 0.000 description 5
- 239000011550 stock solution Substances 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 239000004599 antimicrobial Substances 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 239000012496 blank sample Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 238000011208 chromatographic data Methods 0.000 description 4
- 239000006184 cosolvent Substances 0.000 description 4
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
- 239000013583 drug formulation Substances 0.000 description 4
- 230000001408 fungistatic effect Effects 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 4
- 238000007913 intrathecal administration Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 235000016236 parenteral nutrition Nutrition 0.000 description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
- 229940068968 polysorbate 80 Drugs 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 241000228212 Aspergillus Species 0.000 description 3
- 235000010469 Glycine max Nutrition 0.000 description 3
- 208000009329 Graft vs Host Disease Diseases 0.000 description 3
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 229960005475 antiinfective agent Drugs 0.000 description 3
- 239000003125 aqueous solvent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000012754 cardiac puncture Methods 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000002144 chemical decomposition reaction Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- 208000024908 graft versus host disease Diseases 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 229940028435 intralipid Drugs 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 229960003439 mebendazole Drugs 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 239000008389 polyethoxylated castor oil Substances 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000000932 sedative agent Substances 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 230000003381 solubilizing effect Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 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
- 241001225321 Aspergillus fumigatus Species 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- 206010006473 Bronchopulmonary aspergillosis Diseases 0.000 description 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 2
- 108010078777 Colistin Proteins 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 108010049047 Echinocandins Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010064147 Gastrointestinal inflammation Diseases 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 241000228402 Histoplasma Species 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108010093965 Polymyxin B Proteins 0.000 description 2
- 208000004430 Pulmonary Aspergillosis Diseases 0.000 description 2
- 102220569751 Pyridoxal-dependent decarboxylase domain-containing protein 1_M38A_mutation Human genes 0.000 description 2
- 229940123237 Taxane Drugs 0.000 description 2
- 206010061418 Zygomycosis Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000000735 allogeneic effect Effects 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
- 229940035674 anesthetics Drugs 0.000 description 2
- 229940045799 anthracyclines and related substance Drugs 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 229940045985 antineoplastic platinum compound Drugs 0.000 description 2
- 239000000164 antipsychotic agent Substances 0.000 description 2
- 229940005529 antipsychotics Drugs 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 229940091771 aspergillus fumigatus Drugs 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 150000001557 benzodiazepines Chemical class 0.000 description 2
- 229960001561 bleomycin Drugs 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229960003346 colistin Drugs 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000010579 first pass effect Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 208000018925 gastrointestinal mucositis Diseases 0.000 description 2
- 238000002695 general anesthesia Methods 0.000 description 2
- 239000003193 general anesthetic agent Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003871 intestinal function Effects 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BAXLBXFAUKGCDY-UHFFFAOYSA-N mebendazole Chemical compound [CH]1C2=NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CC=C1 BAXLBXFAUKGCDY-UHFFFAOYSA-N 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 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 2
- 229960003255 natamycin Drugs 0.000 description 2
- 239000004311 natamycin Substances 0.000 description 2
- 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 2
- 235000010298 natamycin Nutrition 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 235000021542 oral nutrition Nutrition 0.000 description 2
- 239000006201 parenteral dosage form Substances 0.000 description 2
- 150000003058 platinum compounds Chemical class 0.000 description 2
- 150000004291 polyenes Chemical class 0.000 description 2
- 229920000024 polymyxin B Polymers 0.000 description 2
- 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 2
- 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 2
- 229960005266 polymyxin b Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 150000003138 primary alcohols Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000006920 protein precipitation Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 229940125723 sedative agent Drugs 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 230000001839 systemic circulation Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical class COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 1
- NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 description 1
- JKXYOQDLERSFPT-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-octadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO JKXYOQDLERSFPT-UHFFFAOYSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 1
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 1
- 208000032529 Accidental overdose Diseases 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 208000003241 Fat Embolism Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 206010057212 Hepatitis viral infections Diseases 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101710108470 Hyalin Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 208000021251 Methanol poisoning Diseases 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 208000010195 Onychomycosis Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 229920002642 Polysorbate 65 Polymers 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 241000235402 Rhizomucor Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 206010046914 Vaginal infection Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 201000007096 Vulvovaginal Candidiasis Diseases 0.000 description 1
- 206010064899 Vulvovaginal mycotic infection Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000000729 antidote Substances 0.000 description 1
- 238000011483 antifungal activity assay Methods 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000007980 azole derivatives Chemical class 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 238000013142 basic testing Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- CFOYWRHIYXMDOT-UHFFFAOYSA-N carbimazole Chemical compound CCOC(=O)N1C=CN(C)C1=S CFOYWRHIYXMDOT-UHFFFAOYSA-N 0.000 description 1
- 229960001704 carbimazole Drugs 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 229940124301 concurrent medication Drugs 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 230000002198 cosolvency Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- SYELZBGXAIXKHU-UHFFFAOYSA-N dodecyldimethylamine N-oxide Chemical compound CCCCCCCCCCCC[N+](C)(C)[O-] SYELZBGXAIXKHU-UHFFFAOYSA-N 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000002786 epipodophyllotoxin derivative Substances 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 244000144992 flock Species 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 210000004276 hyalin Anatomy 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000002071 myeloproliferative effect Effects 0.000 description 1
- 210000000282 nail Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229940087419 nonoxynol-9 Drugs 0.000 description 1
- 229920004918 nonoxynol-9 Polymers 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000003715 nutritional status Nutrition 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940099511 polysorbate 65 Drugs 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000009101 premedication Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000011896 sensitive detection Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008337 systemic blood flow Effects 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- FBWNMEQMRUMQSO-UHFFFAOYSA-N tergitol NP-9 Chemical compound CCCCCCCCCC1=CC=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCO)C=C1 FBWNMEQMRUMQSO-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 201000005882 tinea unguium Diseases 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 210000004906 toe nail Anatomy 0.000 description 1
- 231100000155 toxicity by organ Toxicity 0.000 description 1
- 230000007675 toxicity by organ Effects 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 239000006200 vaporizer Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000010792 warming Methods 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/417—Imidazole-alkylamines, e.g. histamine, phentolamine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Oncology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42393710P | 2010-12-16 | 2010-12-16 | |
| US61/423,937 | 2010-12-16 | ||
| US201161509154P | 2011-07-19 | 2011-07-19 | |
| US61/509,154 | 2011-07-19 | ||
| PCT/US2011/065422 WO2012083138A2 (en) | 2010-12-16 | 2011-12-16 | Azole pharmaceutical formulations for parenteral administration and methods for preparing and using the same as treatment of diseases sensitive to azole compounds |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017013634A Division JP6529527B2 (ja) | 2010-12-16 | 2017-01-27 | 非経口投与のためのアゾール医薬製剤ならびにその調製方法およびアゾール化合物に対して感受性の疾患の処置としてのその使用方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013545819A JP2013545819A (ja) | 2013-12-26 |
| JP2013545819A5 JP2013545819A5 (enExample) | 2015-02-05 |
| JP6086539B2 true JP6086539B2 (ja) | 2017-03-01 |
Family
ID=46245384
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013544816A Expired - Fee Related JP6086539B2 (ja) | 2010-12-16 | 2011-12-16 | 非経口投与のためのアゾール医薬製剤ならびにその調製方法およびアゾール化合物に対して感受性の疾患の処置としてのその使用方法 |
| JP2017013634A Expired - Fee Related JP6529527B2 (ja) | 2010-12-16 | 2017-01-27 | 非経口投与のためのアゾール医薬製剤ならびにその調製方法およびアゾール化合物に対して感受性の疾患の処置としてのその使用方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017013634A Expired - Fee Related JP6529527B2 (ja) | 2010-12-16 | 2017-01-27 | 非経口投与のためのアゾール医薬製剤ならびにその調製方法およびアゾール化合物に対して感受性の疾患の処置としてのその使用方法 |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US10307418B2 (enExample) |
| EP (1) | EP2651450B1 (enExample) |
| JP (2) | JP6086539B2 (enExample) |
| CN (1) | CN103402543B (enExample) |
| AU (1) | AU2011343576B2 (enExample) |
| BR (1) | BR112013015085A8 (enExample) |
| CA (1) | CA2821823C (enExample) |
| DK (1) | DK2651450T3 (enExample) |
| ES (1) | ES2565353T3 (enExample) |
| HU (1) | HUE028667T2 (enExample) |
| IL (1) | IL226977A (enExample) |
| MX (1) | MX337364B (enExample) |
| NZ (1) | NZ613167A (enExample) |
| RU (2) | RU2618456C2 (enExample) |
| WO (1) | WO2012083138A2 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ613167A (en) * | 2010-12-16 | 2015-09-25 | Univ Texas | Azole pharmaceutical formulations for parenteral administration and methods for preparing and using the same as treatment of diseases sensitive to azole compounds |
| ES2822350T3 (es) * | 2011-04-28 | 2021-04-30 | Platform Brightworks Two Ltd | Formulaciones parenterales mejoradas de agentes farmacéuticos lipófilos y procedimientos de preparación y uso de las mismas |
| SG11201504976UA (en) * | 2012-12-28 | 2015-07-30 | Suntory Holdings Ltd | Non-alcohol, beer-taste beverage having shimari in taste |
| CN105394045B (zh) * | 2014-09-04 | 2020-02-14 | 中国科学院上海巴斯德研究所 | 一种肠道病毒的小分子化合物抑制剂及其应用 |
| CN105943500B (zh) * | 2016-07-08 | 2019-01-04 | 河南省立眼科医院 | 一种含有艾沙康唑的眼用纳米胶束抗真菌溶液 |
| TWI834808B (zh) | 2019-02-19 | 2024-03-11 | 西班牙商薩爾瓦特實驗室有限公司 | 以單劑包裝的克氯黴唑液體組成物 |
| CN111665301A (zh) * | 2020-05-29 | 2020-09-15 | 南京品生医疗科技有限公司 | 超高效液相色谱串联质谱技术检测血清中抗真菌药物的试剂盒 |
| CN116507319A (zh) * | 2020-11-16 | 2023-07-28 | W.L.戈尔及同仁股份有限公司 | 不含浊点的制剂、方法和预填充多剂量注射装置 |
| CN113671086B (zh) * | 2021-08-31 | 2023-06-16 | 重庆华邦制药有限公司 | 分离、测定泊沙康唑z2及其杂质的方法 |
| CN114660200A (zh) * | 2022-03-29 | 2022-06-24 | 中国人民解放军总医院 | 一种高效液相色谱串联质谱技术同时测定血浆中4种三唑类抗真菌药物的方法 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4912124A (en) * | 1984-02-23 | 1990-03-27 | Ortho Pharmaceutical Corporation | Antifungal dermatological solution |
| DE3702105A1 (de) | 1987-01-24 | 1988-08-04 | Bayer Ag | Parenterale loesung |
| JPH01242525A (ja) | 1988-03-25 | 1989-09-27 | Nippon Nohyaku Co Ltd | 抗真菌外用剤 |
| PH30929A (en) * | 1992-09-03 | 1997-12-23 | Janssen Pharmaceutica Nv | Beads having a core coated with an antifungal and a polymer. |
| PH31594A (en) * | 1993-09-30 | 1998-11-03 | Janssen Pharmaceutica Nv | Oral formulations on an antifungal. |
| KR0159730B1 (ko) * | 1996-01-15 | 1998-12-01 | 손경식 | 케토코나졸 수성 제제 |
| US7179475B1 (en) * | 1998-12-04 | 2007-02-20 | Johnson & Johnson Consumer Companies, Inc. | Anhydrous topical skin preparations |
| US6362172B2 (en) * | 2000-01-20 | 2002-03-26 | Bristol-Myers Squibb Company | Water soluble prodrugs of azole compounds |
| GB2365770B (en) | 2000-08-18 | 2002-07-31 | Diomed Dev Ltd | Antifungal ketoconazole composition for topical use |
| US20050048126A1 (en) * | 2000-12-22 | 2005-03-03 | Barrett Rabinow | Formulation to render an antimicrobial drug potent against organisms normally considered to be resistant to the drug |
| US20030072807A1 (en) * | 2000-12-22 | 2003-04-17 | Wong Joseph Chung-Tak | Solid particulate antifungal compositions for pharmaceutical use |
| JP2002322056A (ja) | 2001-04-27 | 2002-11-08 | Nippon Kayaku Co Ltd | トリアゾール誘導体の溶液製剤 |
| JP4263441B2 (ja) * | 2002-08-07 | 2009-05-13 | 富士重工業株式会社 | ４輪駆動車の制御装置 |
| WO2004014431A1 (en) | 2002-08-12 | 2004-02-19 | Ranbaxy Laboratories Limited | A parenteral dosage form of selective cox-2 inhibitors |
| ZA200409537B (en) | 2003-01-31 | 2006-10-25 | Yamanouchi Pharma Co Ltd | Stable solid medicinal composition for oral administration |
| US20060003654A1 (en) * | 2004-06-30 | 2006-01-05 | Lostocco Michael R | Dispersible alcohol/cleaning wipes via topical or wet-end application of acrylamide or vinylamide/amine polymers |
| WO2006105399A1 (en) | 2005-03-31 | 2006-10-05 | Bristol-Myers Squibb Company | Methods for administering ixabepilone |
| CA2613389A1 (en) | 2005-06-27 | 2007-01-04 | Barrier Therapeutics, Inc. | Micogel topical formulations |
| US20070082870A1 (en) * | 2005-10-11 | 2007-04-12 | Buchanan Charles M | Pharmaceutical formulations of cyclodextrins and antifungal azole compounds |
| AU2007355106A1 (en) * | 2006-11-29 | 2008-12-18 | Foamix Ltd. | Foamable waterless compositions with modulating agents |
| KR20100075475A (ko) | 2007-09-05 | 2010-07-02 | 가부시키가이샤 폴라 파마 | 의약 조성물 |
| US20090253712A1 (en) | 2008-04-03 | 2009-10-08 | Semmelweis Egyetem | Aqueous solvent system for solubilization of azole compounds |
| WO2009139925A1 (en) * | 2008-05-16 | 2009-11-19 | Panacea Pharmaceuticals, Inc. | Methods for the treatment of brain edema |
| MX2011008204A (es) | 2009-02-05 | 2011-12-06 | Targeted Delivery Technologies Ltd | Metodos para reducir la proliferacion y viabilidad de los agentes microbianos. |
| CN102387785B (zh) | 2009-04-09 | 2017-08-25 | 宝丽制药股份有限公司 | 抗真菌药物组合物 |
| US8252821B2 (en) | 2009-04-14 | 2012-08-28 | Bristol-Myers Squibb Company | Bioavailable capsule compositions of amorphous alpha-(N-sulfonamido)acetamide compound |
| NZ613167A (en) * | 2010-12-16 | 2015-09-25 | Univ Texas | Azole pharmaceutical formulations for parenteral administration and methods for preparing and using the same as treatment of diseases sensitive to azole compounds |
| ES2822350T3 (es) * | 2011-04-28 | 2021-04-30 | Platform Brightworks Two Ltd | Formulaciones parenterales mejoradas de agentes farmacéuticos lipófilos y procedimientos de preparación y uso de las mismas |
-
2011
- 2011-12-16 NZ NZ613167A patent/NZ613167A/en not_active IP Right Cessation
- 2011-12-16 EP EP11849408.7A patent/EP2651450B1/en not_active Not-in-force
- 2011-12-16 DK DK11849408.7T patent/DK2651450T3/en active
- 2011-12-16 RU RU2013132703A patent/RU2618456C2/ru not_active IP Right Cessation
- 2011-12-16 US US13/994,152 patent/US10307418B2/en active Active
- 2011-12-16 ES ES11849408.7T patent/ES2565353T3/es active Active
- 2011-12-16 JP JP2013544816A patent/JP6086539B2/ja not_active Expired - Fee Related
- 2011-12-16 CA CA2821823A patent/CA2821823C/en not_active Expired - Fee Related
- 2011-12-16 WO PCT/US2011/065422 patent/WO2012083138A2/en not_active Ceased
- 2011-12-16 CN CN201180067824.5A patent/CN103402543B/zh not_active Expired - Fee Related
- 2011-12-16 HU HUE11849408A patent/HUE028667T2/en unknown
- 2011-12-16 AU AU2011343576A patent/AU2011343576B2/en not_active Ceased
- 2011-12-16 BR BR112013015085A patent/BR112013015085A8/pt active Search and Examination
- 2011-12-16 MX MX2013006816A patent/MX337364B/es active IP Right Grant
- 2011-12-16 RU RU2016149770A patent/RU2734128C2/ru active
-
2013
- 2013-06-16 IL IL226977A patent/IL226977A/en active IP Right Grant
-
2017
- 2017-01-27 JP JP2017013634A patent/JP6529527B2/ja not_active Expired - Fee Related
-
2019
- 2019-04-16 US US16/385,293 patent/US20190240216A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| RU2016149770A3 (enExample) | 2020-02-04 |
| JP2013545819A (ja) | 2013-12-26 |
| CN103402543B (zh) | 2015-09-16 |
| RU2734128C2 (ru) | 2020-10-13 |
| IL226977A (en) | 2017-01-31 |
| RU2618456C2 (ru) | 2017-05-03 |
| CN103402543A (zh) | 2013-11-20 |
| ES2565353T3 (es) | 2016-04-04 |
| MX337364B (es) | 2016-02-29 |
| HK1190643A1 (zh) | 2014-07-11 |
| US20140031366A1 (en) | 2014-01-30 |
| CA2821823C (en) | 2019-05-07 |
| NZ613167A (en) | 2015-09-25 |
| BR112013015085A8 (pt) | 2018-04-03 |
| BR112013015085A2 (pt) | 2016-08-09 |
| RU2013132703A (ru) | 2015-01-27 |
| US20190240216A1 (en) | 2019-08-08 |
| WO2012083138A2 (en) | 2012-06-21 |
| HUE028667T2 (en) | 2016-12-28 |
| EP2651450A2 (en) | 2013-10-23 |
| EP2651450A4 (en) | 2014-07-09 |
| DK2651450T3 (en) | 2016-03-14 |
| WO2012083138A3 (en) | 2012-11-01 |
| RU2016149770A (ru) | 2018-11-05 |
| JP2017114869A (ja) | 2017-06-29 |
| AU2011343576A1 (en) | 2013-07-11 |
| JP6529527B2 (ja) | 2019-06-12 |
| MX2013006816A (es) | 2013-11-01 |
| CA2821823A1 (en) | 2012-06-21 |
| AU2011343576B2 (en) | 2016-09-08 |
| EP2651450B1 (en) | 2015-12-16 |
| US10307418B2 (en) | 2019-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6086539B2 (ja) | 非経口投与のためのアゾール医薬製剤ならびにその調製方法およびアゾール化合物に対して感受性の疾患の処置としてのその使用方法 | |
| Willems et al. | Itraconazole oral solution and intravenous formulations: a review of pharmacokinetics and pharmacodynamics | |
| Bellmann | Clinical pharmacokinetics of systemically administered antimycotics | |
| JP6008849B2 (ja) | 置換β−シクロデキストリンにより安定化されたポサコナゾール静脈注射用溶液製剤 | |
| KR101502533B1 (ko) | 우수한 안정성을 갖는 택산 유도체 함유 주사제용동결건조 조성물 및 이의 제조방법 | |
| EP2827862B1 (en) | Formulations of bendamustine | |
| WO2022160971A1 (zh) | 一种含有难溶性药物的浓缩液以及由其制备的乳剂 | |
| Khan et al. | Additive potential of combination therapy against cryptococcosis employing a novel amphotericin B and fluconazole loaded dual delivery system | |
| Orosz | Antifungal drug therapy in avian species | |
| AU2011302885B2 (en) | Non-aqueous oily injectable formulation exhibiting preservative efficacy | |
| Kaur et al. | Nascent Nanoformulations as an insight into the limitations of the conventional systemic antifungal therapies | |
| US20030082229A1 (en) | Parenteral chlorambucil for treatment of malignant and autoimmune disease and methods of use | |
| Tell et al. | Studies on itraconazole delivery and pharmacokinetics in mallard ducks (Anas platyrhynchos) | |
| JPWO2002098463A1 (ja) | 抗真菌組成物 | |
| HK1190643B (en) | Azole pharmaceutical formulations for parenteral administration and methods for preparing and using the same as treatment of diseases sensitive to azole compounds | |
| RU2575768C2 (ru) | Составы внутривенных растворов позаконазола, стабилизированные посредством замещенного бета-циклодекстрина |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141210 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20141210 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20150917 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150929 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20151210 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20151224 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20151210 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160126 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160226 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20160226 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160721 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161019 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20161202 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161231 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20170106 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20170106 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170127 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6086539 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |