JP5518280B2 - 単離した斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸を薬学的に許容しうる担体または賦形剤と共に含む組成物、および単離した斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸 - Google Patents
単離した斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸を薬学的に許容しうる担体または賦形剤と共に含む組成物、および単離した斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸 Download PDFInfo
- Publication number
- JP5518280B2 JP5518280B2 JP2006517585A JP2006517585A JP5518280B2 JP 5518280 B2 JP5518280 B2 JP 5518280B2 JP 2006517585 A JP2006517585 A JP 2006517585A JP 2006517585 A JP2006517585 A JP 2006517585A JP 5518280 B2 JP5518280 B2 JP 5518280B2
- Authority
- JP
- Japan
- Prior art keywords
- acetyl
- hydroxy
- propylphenoxy
- propylphenylthio
- propoxy
- 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 - Lifetime
Links
- 239000000203 mixture Substances 0.000 title claims description 36
- KPWYNAGOBXLMSE-UHFFFAOYSA-N Tipelukast Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(OCCCC(O)=O)=C1CCC KPWYNAGOBXLMSE-UHFFFAOYSA-N 0.000 title claims description 23
- 239000000546 pharmaceutical excipient Substances 0.000 title claims description 13
- 239000003937 drug carrier Substances 0.000 title claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 239000013078 crystal Substances 0.000 claims description 23
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 8
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 8
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 8
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 7
- 239000008101 lactose Substances 0.000 claims description 7
- -1 4-acetyl-3-hydroxy-2-propylphenylthio Chemical group 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 8
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 description 31
- 239000003826 tablet Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000011230 binding agent Substances 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 238000000576 coating method Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 238000007908 dry granulation Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 238000005550 wet granulation Methods 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000007891 compressed tablet Substances 0.000 description 3
- 238000007907 direct compression Methods 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- 241000220479 Acacia Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- OZKSBPMWKLECHO-UHFFFAOYSA-N ethyl 4-[6-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenyl)sulfanylpropoxy]-2-propylphenoxy]butanoate Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(OCCCC(=O)OCC)=C1CCC OZKSBPMWKLECHO-UHFFFAOYSA-N 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229940049654 glyceryl behenate Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 150000002617 leukotrienes Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000001144 powder X-ray diffraction data Methods 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000010802 sludge Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 235000010215 titanium dioxide Nutrition 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- KNQROEPUZNODJT-UHFFFAOYSA-N 1-[4-(3-bromopropylsulfanyl)-2-hydroxy-3-propylphenyl]ethanone Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1SCCCBr KNQROEPUZNODJT-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 1
- 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 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical compound O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229920001688 coating polymer Polymers 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940057307 dihydrate calcium sulfate Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000007580 dry-mixing Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- MEFUYKDJCOTBGV-UHFFFAOYSA-N ethyl 4-(6-acetyl-3-hydroxy-2-propylphenoxy)butanoate Chemical compound CCCC1=C(O)C=CC(C(C)=O)=C1OCCCC(=O)OCC MEFUYKDJCOTBGV-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-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
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000011410 subtraction method Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/22—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/20—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
発明の分野
4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸の、粉末X線回折で定義される多形形態Aは、他の結晶形態に比べて、高い溶解度と生物学的利用能を有する。
ロイコトリエンは、5’−リポキシゲナーゼ経路を介してのアラキドン酸の代謝物であり、気管支喘息に関係するような、アレルギー反応の重要なメディエーターである。ロイコトリエンに拮抗効果を発揮する薬物は、アレルギー疾患の処置に有用である。
本発明は、選択された結晶形態での式(1):
式(2):
4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸エチルの合成
4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸の合成
結晶多形性
斜方多形結晶型V(形態A)を得るための大量結晶化手順
一般に、湿式造粒錠剤は、ヒドロキシプロピルセルロースの水溶液からなる結合剤溶液を用いて製造された。造粒は、高剪断造粒機で行われ、得られた湿潤物を流動床で乾燥し、粉末化し、崩壊、流動および圧縮を助ける粒状外(extragranular)賦形剤と混合し、引き続いて錠剤プレスで錠剤化した。これらのコア錠剤を、フィルムコーティングして、外観を標準化し、コンプライアンス(すなわち、飲み込みの容易さ)を改善した。賦形剤として、クロスカルメロースナトリウム、ステアリン酸マグネシウム、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ラクトース、ベヘン酸グリセリル、ポリビニルピロリドン、マンニトール、二酸化チタンおよび微結晶性セルロースが挙げられるが、それらに限定されない。
一般に、乾式造粒処方物は、結合剤粉末、崩壊剤粉末および潤滑剤粉末の一部を、(タンブルブレンダーまたは高剪断ミキサー中で)乾燥混合することにより形成された。この乾燥粉末ブレンドを、揺動(剪断)造粒機を備えたローラー圧縮機を用いて、粒状物に成形した。ssメッシュ篩、ギャップ幅、ギャップ力、ローラー速度および造粒機速度は、医薬加工の当業者に明白なように、処方用物理パラメーターが最適化されるべく決定された。賦形剤として、クロスカルメロースナトリウム、ステアリン酸マグネシウム、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ラクトース、ベヘン酸グリセリル、ポリビニルピロリドン、マンニトール、二酸化チタンおよび微結晶性セルロースが挙げられるが、それらに限定されない。
乾式造粒のための特定の処方
湿式造粒のための特定の処方
試料は、通常の前面充填(frontpacking)法により調製し、Siemens D5000回折計システムで検査した。高解像度Cu−Kα源を使用し、50kV/35mAで操作した。二次ビームは、Kevex固相検出器で単色化した。データ収集のために、2.5°〜35°(2θ)の範囲内で、段階的走査モードを使用した。得られたデータを、Diffrac Plus(商標)ソフトウエアで処理した。
Claims (5)
- 単離した斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸を薬学的に許容しうる担体または賦形剤と共に含む組成物であって、
前記斜方晶が、温エタノール5〜10重量部と水1〜10部に、4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸を溶解し、得られた懸濁液を20〜25℃で15〜60分間攪拌し、次いで5〜10℃にさらに1〜4時間冷却し、水5〜15部を添加し、混合物を5〜10℃でさらに1〜4時間攪拌し、斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸を単離することによって調製され、前記斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸が9°2θの領域における粉末X線回折(PXRD)ピーク高さによって規定される多形形態を持つ
組成物。 - 錠剤又はカプセルの形態にある、請求項1に記載の組成物。
- ラクトースと微結晶性セルロースをさらに含む、請求項1に記載の組成物。
- 250〜500mgの間の重さを有する、請求項2に記載の組成物。
- 温エタノール5〜10重量部と水1〜10部に、4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸を溶解し、得られた懸濁液を20〜25℃で15〜60分間攪拌し、次いで5〜10℃にさらに1〜4時間冷却し、水5〜15部を添加し、混合物を5〜10℃でさらに1〜4時間攪拌し、斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸を単離することによって調製され、前記斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸が9°2θの領域における粉末X線回折(PXRD)ピーク高さによって規定される多形形態を持つ、
単離した斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/601,862 US7064146B2 (en) | 2003-06-24 | 2003-06-24 | Pharmaceutical compositions of isolated orthorhombic crystalline 4-[6-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenylthio)propoxy]-2-propylphenoxy]butyric acid and methods of use |
US10/601,862 | 2003-06-24 | ||
PCT/US2004/020154 WO2005000243A2 (en) | 2003-06-24 | 2004-06-24 | The polymorphic form a of 4-[6-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenylthio)propoxy]-2-propylphenoxy]butryric acid |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013265114A Division JP2014097989A (ja) | 2003-06-24 | 2013-12-24 | 4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸の多形形態a |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2007524624A JP2007524624A (ja) | 2007-08-30 |
JP5518280B2 true JP5518280B2 (ja) | 2014-06-11 |
Family
ID=33539463
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006517585A Expired - Lifetime JP5518280B2 (ja) | 2003-06-24 | 2004-06-24 | 単離した斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸を薬学的に許容しうる担体または賦形剤と共に含む組成物、および単離した斜方晶4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸 |
JP2013265114A Pending JP2014097989A (ja) | 2003-06-24 | 2013-12-24 | 4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸の多形形態a |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013265114A Pending JP2014097989A (ja) | 2003-06-24 | 2013-12-24 | 4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸の多形形態a |
Country Status (11)
Country | Link |
---|---|
US (3) | US7064146B2 (ja) |
EP (1) | EP1636176A4 (ja) |
JP (2) | JP5518280B2 (ja) |
KR (1) | KR101120408B1 (ja) |
CN (1) | CN1812968B (ja) |
BR (1) | BRPI0411973A (ja) |
CA (1) | CA2530583C (ja) |
NO (1) | NO20060379L (ja) |
NZ (1) | NZ544319A (ja) |
RU (1) | RU2317979C2 (ja) |
WO (1) | WO2005000243A2 (ja) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7060854B2 (en) * | 2003-06-24 | 2006-06-13 | Medicinova, Inc. | Process for making polymorphic form A of 4-[6-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenylthio)propoxy]-2-propylphenoxy]butyric acid |
US7064146B2 (en) * | 2003-06-24 | 2006-06-20 | Medicinova, Inc. | Pharmaceutical compositions of isolated orthorhombic crystalline 4-[6-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenylthio)propoxy]-2-propylphenoxy]butyric acid and methods of use |
RU2388466C2 (ru) | 2004-04-27 | 2010-05-10 | Медисинова, Инк. | Производные феноксиалкилкарбоновых кислот при лечении воспалительных заболеваний |
US8962687B2 (en) | 2012-12-05 | 2015-02-24 | Medicinova, Inc. | Method of treating liver disorders |
JP2013119550A (ja) * | 2011-12-08 | 2013-06-17 | Medicinova Inc | 非アルコール性脂肪性肝疾患及び非アルコール性脂肪性肝炎の処置方法 |
CA2917780C (en) | 2013-07-25 | 2023-01-24 | Medicinova, Inc. | Methods for reducing triglyceride, total cholesterol and low density lipoprotein blood levels |
US9346754B2 (en) | 2014-05-08 | 2016-05-24 | Medicinova, Inc. | Method of treating advanced non-alcoholic steatohepatitis |
US20150321989A1 (en) * | 2014-05-08 | 2015-11-12 | Medicinova, Inc. | Method of treating idiopathic pulmonary fibrosis |
ES2957213T3 (es) * | 2014-06-02 | 2024-01-15 | Medicinova Inc | Método para inhibir o tratar la fibrosis |
CN106535931A (zh) * | 2014-08-25 | 2017-03-22 | 艾慕恩治疗公司 | 卵蛋白制剂及其制备方法 |
WO2016123530A1 (en) * | 2015-01-30 | 2016-08-04 | The Regents Of The University Of Michigan | Compositions and methods for delivering pharmaceutical agents |
EP4346783A1 (en) | 2021-05-28 | 2024-04-10 | MediciNova, Inc. | Phenoxyalkylcarboxylic acid derivatives and their use in lowering triglyceride levels |
WO2024117173A1 (ja) * | 2022-11-30 | 2024-06-06 | 花王株式会社 | 痒みの予防又は改善剤 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5858146A (ja) * | 1981-10-05 | 1983-04-06 | Tanabe Seiyaku Co Ltd | 速放性マイクロカプセル |
US4710384A (en) * | 1986-07-28 | 1987-12-01 | Avner Rotman | Sustained release tablets made from microcapsules |
US4985585A (en) * | 1988-03-07 | 1991-01-15 | Kyorin Pharmaceutical Co., Ltd. | Phenoxyalkylcarboxylic acid derivatives and process for their preparations |
JPH07116125B2 (ja) * | 1988-03-07 | 1995-12-13 | 杏林製薬株式会社 | フェノキシアルキルカルボン酸誘導体及びその製造法 |
US5178878A (en) * | 1989-10-02 | 1993-01-12 | Cima Labs, Inc. | Effervescent dosage form with microparticles |
JPH06345682A (ja) * | 1993-06-11 | 1994-12-20 | Kyorin Pharmaceut Co Ltd | カルボン酸誘導体 |
JP3773064B2 (ja) * | 1994-09-13 | 2006-05-10 | 杏林製薬株式会社 | フェノキシアルキルカルボン酸誘導体の製造法 |
US5639475A (en) * | 1995-02-03 | 1997-06-17 | Eurand America, Incorporated | Effervescent microcapsules |
JPH1179985A (ja) | 1997-09-01 | 1999-03-23 | Kyorin Pharmaceut Co Ltd | 喘息治療用の粉末吸入剤 |
US7060854B2 (en) * | 2003-06-24 | 2006-06-13 | Medicinova, Inc. | Process for making polymorphic form A of 4-[6-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenylthio)propoxy]-2-propylphenoxy]butyric acid |
US7064146B2 (en) * | 2003-06-24 | 2006-06-20 | Medicinova, Inc. | Pharmaceutical compositions of isolated orthorhombic crystalline 4-[6-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenylthio)propoxy]-2-propylphenoxy]butyric acid and methods of use |
-
2003
- 2003-06-24 US US10/601,862 patent/US7064146B2/en not_active Expired - Lifetime
-
2004
- 2004-06-24 CA CA2530583A patent/CA2530583C/en not_active Expired - Fee Related
- 2004-06-24 CN CN200480017934.0A patent/CN1812968B/zh not_active Expired - Lifetime
- 2004-06-24 KR KR1020057024889A patent/KR101120408B1/ko active IP Right Grant
- 2004-06-24 JP JP2006517585A patent/JP5518280B2/ja not_active Expired - Lifetime
- 2004-06-24 EP EP04776980A patent/EP1636176A4/en not_active Withdrawn
- 2004-06-24 BR BRPI0411973-8A patent/BRPI0411973A/pt not_active IP Right Cessation
- 2004-06-24 NZ NZ544319A patent/NZ544319A/en not_active IP Right Cessation
- 2004-06-24 RU RU2006101871/04A patent/RU2317979C2/ru not_active IP Right Cessation
- 2004-06-24 WO PCT/US2004/020154 patent/WO2005000243A2/en active Application Filing
-
2005
- 2005-12-29 US US11/319,272 patent/US7365224B2/en not_active Expired - Lifetime
-
2006
- 2006-01-24 NO NO20060379A patent/NO20060379L/no not_active Application Discontinuation
-
2008
- 2008-04-21 US US12/106,939 patent/US7728169B2/en not_active Expired - Lifetime
-
2013
- 2013-12-24 JP JP2013265114A patent/JP2014097989A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
KR20060030484A (ko) | 2006-04-10 |
JP2014097989A (ja) | 2014-05-29 |
CN1812968A (zh) | 2006-08-02 |
JP2007524624A (ja) | 2007-08-30 |
RU2317979C2 (ru) | 2008-02-27 |
US7728169B2 (en) | 2010-06-01 |
US7064146B2 (en) | 2006-06-20 |
US20060135604A1 (en) | 2006-06-22 |
BRPI0411973A (pt) | 2006-08-29 |
EP1636176A4 (en) | 2010-03-31 |
CA2530583C (en) | 2010-08-10 |
KR101120408B1 (ko) | 2012-03-15 |
NO20060379L (no) | 2006-03-24 |
EP1636176A2 (en) | 2006-03-22 |
WO2005000243A3 (en) | 2005-04-28 |
US20040266878A1 (en) | 2004-12-30 |
US20080292698A1 (en) | 2008-11-27 |
US7365224B2 (en) | 2008-04-29 |
CA2530583A1 (en) | 2005-01-06 |
RU2006101871A (ru) | 2006-07-27 |
NZ544319A (en) | 2008-12-24 |
WO2005000243A2 (en) | 2005-01-06 |
CN1812968B (zh) | 2016-07-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2014097989A (ja) | 4−[6−アセチル−3−[3−(4−アセチル−3−ヒドロキシ−2−プロピルフェニルチオ)プロポキシ]−2−プロピルフェノキシ]酪酸の多形形態a | |
US7153993B2 (en) | Process for making polymorphic form A of 4-[6-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenylthio)propoxy]-2-propylphenoxy]butyric acid | |
AU2020276701B2 (en) | Crystalline forms of N-[4-(Chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide | |
US20170226119A1 (en) | Solid salt form of alpha-6-mpeg6-o-hydroxycodone as opioid agonists and uses thereof | |
JP2018035186A (ja) | ベンゾチアゾロン化合物を含む製剤 | |
AU2009321385A1 (en) | Novel processes and pure polymorphs | |
AU2004251744B2 (en) | The polymorphic Form A of 4-[6-acetyl-3-[3-(4-acetyl-3-hydroxy-2-propylphenylthio)propoxy]-2-propylphenoxy]butryric acid | |
MXPA06000083A (en) | The polymorphic form a of 4-[6 -acetyl -3-[3-(4-acetyl -3-hydroxy-2 -propylphenylthio) propoxy]-2- propylphenoxy]butryric acid | |
JPH10265387A (ja) | 腎炎治療剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090901 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091130 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20101130 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130920 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130926 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131021 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131024 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131125 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131128 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131224 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140402 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5518280 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |