JP2000505463A - 置換されたカルボン酸タイプのアニオン非麻薬性鎮痛薬であるモルヒネ塩及びジアモルヒネ塩 - Google Patents
置換されたカルボン酸タイプのアニオン非麻薬性鎮痛薬であるモルヒネ塩及びジアモルヒネ塩Info
- Publication number
- JP2000505463A JP2000505463A JP9530547A JP53054797A JP2000505463A JP 2000505463 A JP2000505463 A JP 2000505463A JP 9530547 A JP9530547 A JP 9530547A JP 53054797 A JP53054797 A JP 53054797A JP 2000505463 A JP2000505463 A JP 2000505463A
- Authority
- JP
- Japan
- Prior art keywords
- salt
- formula
- narcotic analgesic
- carboxylic acid
- base
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000003839 salts Chemical class 0.000 title claims abstract description 85
- 239000000730 antalgic agent Substances 0.000 title claims abstract description 32
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title claims abstract description 27
- 125000000129 anionic group Chemical group 0.000 title claims abstract description 13
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 title abstract description 59
- 229960005181 morphine Drugs 0.000 title abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 31
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229960001259 diclofenac Drugs 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- 229940079593 drug Drugs 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 208000002193 Pain Diseases 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 239000004084 narcotic analgesic agent Substances 0.000 claims description 12
- -1 alkyl ketones Chemical class 0.000 claims description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 229940035676 analgesics Drugs 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 230000000202 analgesic effect Effects 0.000 claims description 5
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 5
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 5
- 239000000284 extract Substances 0.000 claims description 5
- 150000002576 ketones Chemical class 0.000 claims description 5
- 229910052751 metal Chemical class 0.000 claims description 5
- 239000002184 metal Chemical class 0.000 claims description 5
- 150000003462 sulfoxides Chemical class 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 150000002170 ethers Chemical class 0.000 claims description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- 230000003533 narcotic effect Effects 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 238000007911 parenteral administration Methods 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000005215 alkyl ethers Chemical class 0.000 claims description 3
- 125000002091 cationic group Chemical group 0.000 claims description 3
- 150000004292 cyclic ethers Chemical class 0.000 claims description 3
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 claims description 3
- 229960001395 fenbufen Drugs 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- 238000011200 topical administration Methods 0.000 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 2
- 241000282412 Homo Species 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 239000003463 adsorbent Substances 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- 159000000007 calcium salts Chemical class 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000006260 foam Substances 0.000 claims description 2
- 229960000905 indomethacin Drugs 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 2
- 229960000991 ketoprofen Drugs 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 claims description 2
- 229960000894 sulindac Drugs 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims 3
- VJFNENWSKBLQDJ-ZVAWYAOSSA-N 6-[(s)-hydroxy-(4-methoxy-6-methyl-7,8-dihydro-5h-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)methyl]-2,3-dimethoxybenzoic acid Chemical compound OC(=O)C1=C(OC)C(OC)=CC=C1[C@H](O)C1C2=C(OC)C(OCO3)=C3C=C2CCN1C VJFNENWSKBLQDJ-ZVAWYAOSSA-N 0.000 claims 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 1
- 159000000021 acetate salts Chemical class 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 150000001447 alkali salts Chemical class 0.000 claims 1
- 229930013930 alkaloid Natural products 0.000 claims 1
- 150000003797 alkaloid derivatives Chemical class 0.000 claims 1
- 125000005599 alkyl carboxylate group Chemical group 0.000 claims 1
- 239000011575 calcium Substances 0.000 claims 1
- 230000000295 complement effect Effects 0.000 claims 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000000376 reactant Substances 0.000 claims 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical class O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 abstract description 19
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 239000013543 active substance Substances 0.000 description 17
- 229960002069 diamorphine Drugs 0.000 description 12
- 239000000243 solution Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 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 3
- 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 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical class [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 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 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 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 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 125000005360 alkyl sulfoxide group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 235000013681 dietary sucrose Nutrition 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SDEBYHVDMCQKNZ-UHFFFAOYSA-N 4-methoxy-6-piperazin-1-ylpyrimidine;hydrochloride Chemical compound Cl.C1=NC(OC)=CC(N2CCNCC2)=N1 SDEBYHVDMCQKNZ-UHFFFAOYSA-N 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 241000219745 Lupinus Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 244000000231 Sesamum indicum Species 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
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 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 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical class CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 208000008013 morphine dependence Diseases 0.000 description 1
- 229960005195 morphine hydrochloride Drugs 0.000 description 1
- XELXKCKNPPSFNN-BJWPBXOKSA-N morphine hydrochloride trihydrate Chemical compound O.O.O.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O XELXKCKNPPSFNN-BJWPBXOKSA-N 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 150000003901 oxalic acid esters Chemical class 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000009993 protective function Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
- C07D489/04—Salts; Organic complexes
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. アニオン非麻薬性の酸によるカチオン麻薬性鎮痛薬の塩であって、前記麻 薬性鎮痛薬の塩基が式3(但し、Rは、HまたはCH3COを表す)を満たし、 前記非麻薬性鎮痛薬が、置換されたカルボン酸タイプに属することを特徴とする 塩。 2. 置換されたカルボン酸タイプの非麻薬性鎮痛薬のアニオンが、ジクロフェ ナク、インドメタシン、スリンダク、ケトプロフェンまたはフェンブフェン、好 ましくは、ジクロフェナクであることを特徴とする請求項1に記載の塩。 3. 請求項1または2に記載された塩の製造方法であって、前記麻薬性鎮痛薬 の前記塩基が、式3を満たし、この式においてRは、HもしくはCH3COまた はそれらの好適な塩を表し、不活性ガス中、0〜100℃の温度範囲で前記塩を 置換されたカルボン酸タイプの前記非麻薬制鎮痛薬、またはその塩基性塩と反応 させる方法。 4. 前記置換されたカルボン酸タイプの非麻薬性鎮痛薬の塩を、式3(但し、 Rは、HもしくはCH3COを表す)の麻薬性鎮痛薬の塩基より揮発性もしくは 弱い塩基とともに使用すること、または前記置換されたカルボン酸タイプの非麻 薬性鎮痛薬の塩を、請求項1の塩より溶解しやすい、置換されたカルボン酸タイ プの非麻薬性鎮痛薬で塩類を生成する塩基とともに使用することを特徴とする請 求項3に記載の方法。 5. 有機アンモニウム塩もしくは金属塩、好ましくは、カルシウム塩を、塩と して使用することを特徴とする請求項4に記載の方法。 6. 式3(但し、Rは、HもしくはCH3COを表す)の麻薬性鎮痛薬の塩基 からの塩を、前記置換されたカルボン酸タイプの非麻薬性鎮痛薬の酸より揮発性 もしくは弱い酸とともに使用すること、または、式3(但し、Rは、Hもしくは CH3COを表す)の麻薬性鎮痛薬の塩基からの塩を、金属カチオン類、好まし くは、Ca2+とともに難溶性の塩類を生成する酸とともに使用することを特徴と する請求項3〜5のいずれか1項に記載の方法。 7. 式3(但し、Rは、HもしくはCH3COを表す)の麻薬性鎮痛薬の塩基 からの塩を、無機酸、好ましくは塩酸塩、硫酸塩もしくは酢酸塩とともに使用す ること、または、式3(但し、Rは、HもしくはCH3COを表す)の麻薬性鎮 痛薬の塩基からの塩を、有機酸、好ましくはフマル酸塩、マレイン酸塩、もしく はシュウ酸塩とともに使用することを特徴とする請求項6に記載の方法。 8. 前記置換されたカルボン酸タイプの非麻薬性鎮痛薬の酸として、ジクロフ ェナク([2−[(2,6−ジクロロフェニル)−アミノ]−フェニル]−酢酸)を 使用することを特徴とする請求項3〜7のいずれかに1項に記載の方法。 9. 式3(但し、Rは、HもしくはCH3COを表す)の塩基性麻薬性鎮痛薬 の酸塩、好ましくは、塩酸塩、硫酸塩、酢酸塩が、前記置換されたカルボン酸タ イプの非麻薬性鎮痛薬のエステル、好ましくは低級アルキルエステルと、塩基、 好ましくはNaOHの存在下で、不活性溶媒中で、0〜100℃の範囲の温度で 反応することを特徴とする請求項1または2に記載の塩の製造方法。 10.式3(但し、Rは、HもしくはCH3COを表す)の麻薬性鎮痛薬の塩 基が、前記置換されたカルボン酸タイプの非麻薬性鎮痛薬の酸と、不活性溶媒中 で、0〜100℃の範囲の温度で反応することを特徴とする請求項1または2に 記載の塩の製造方法。 11.式3(但し、Rは、HもしくはCH3COを表す)の麻薬性鎮痛薬の塩基 を、添加物中の生のアルカロイド抽出物として使用することを特徴とする請求項 9または10に記載の塩の製造方法。 12.式3(但し、Rは、HもしくはCH3COを表す)の麻薬性鎮痛薬のカチ オンもしくは塩基、または、置換されたカルボン酸タイプの非麻薬性鎮痛薬のア ニオンもしくは酸が、液体もしくは固体の、荷電もしくは非荷電の、無機もしく は有機の吸着体、好ましくはイオン交換体と結合していること、及び相補的なア ニオンもしくはカチオン成分それぞれと、不活性溶媒中で、0〜100℃の範囲 の温度で反応することを特徴とする請求項1または2に記載の塩の製造方法。 13.少なくとも等モル量の反応物を使用することを特徴とする請求項3〜12 のいずれか1項に記載の方法。 14.前記反応を、室温及び/または不活性ガス雰囲気、好ましくは窒素雰囲気 で行うことを特徴とする請求項3〜13のいずれか1項に記載の方法。 15.不活性溶媒として、アルコール類、エーテル類、ケトン類、カルボン酸エ ステル類、アミド類、スルホキシド類、塩素化炭化水素類、または、これらの溶 媒の混合物を使用することを特徴とする請求項3〜14のいずれか1項に記載の 方法。 16.アルコール類として、低級アルカノール類、好ましくは、メタノールもし くはエタノールを使用し;エーテル類として、ジ−低級アルキルエーテル類もし くは環状エーテル類、好ましくは、ジエチルエーテル、ジオキサンもしくはテト ラヒドロフランを使用し;ケトン類として、ジ−低級アルキルケトン類、好まし くは、アセトンを使用し;カルボン酸エステル類として、低級アルキルカルボン 酸エステル類、好ましくは、酢酸エチルエステルを使用し;アミド類として、N ,N−ジ−低級アルキルアミド類、好ましくは、N,N−ジ−メチルホルムアミ ドを使用し;スルホキシド類として、ジ−低級アルキルスルホキシド類、好まし くは、ジメチルスルホキシドを使用し;塩素化炭化水素類として、メチレンクロ リドもしくはクロロホルムを好ましくは使用すること、または、これらの溶媒の 混合物を使用することを特徴とする請求項3〜15のいずれか1項に記載の方法 。 17.それ自体既知の薬学的アジュバントに加えて、請求項1または2に記載の 塩を含むことを特徴とする薬剤。 18.経腸投与、例えば、経口もしくは直腸内投与のための、または、腸管外投 与、例えば、静脈内、筋肉内、皮下もしくは局所投与のための請求項17に記載 の薬剤。 19.ガレノスフォームにおける薬剤における、または、それらの製造のための 請求項1または2に記載の塩の使用。 20.ヒト及び動物の生体の治療のための請求項1または2に記載の塩。 21.痛みの治療のための請求項1または2に記載の塩。 22.ヒト及びの動物の生体の治療のための請求項17または18に記載の薬剤 。 23.痛みの治療のための請求項17または18に記載の薬剤。 24.ヒト及び動物の生体の治療方法であって、請求項1または2のいずれか1 項に記載の塩、または請求項17または18のいずれか1項に記載の薬剤を使用 することを特徴とする治療方法。 25.痛みの治療方法であって、請求項1または2のいずれかに記載の塩、また は請求項17または18のいずれかに記載の薬剤を使用することを特徴とする治 療方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19607395A DE19607395C2 (de) | 1996-02-28 | 1996-02-28 | Salze aus einem kationischen narkotischen Analgetikum mit einem anionischen nichtnarkotischen Analgetikum, Verfahren zu deren Herstellung und die diese Salze enthaltenden pharmazeutischen Präparate |
DE19607395.2 | 1996-02-28 | ||
PCT/EP1997/000711 WO1997031918A1 (de) | 1996-02-28 | 1997-02-15 | Morphin- und diamorphinsalze anionischer nicht-narkotischer analgetika vom typ der substituierten carbonsäuren |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2000505463A true JP2000505463A (ja) | 2000-05-09 |
JP4624497B2 JP4624497B2 (ja) | 2011-02-02 |
Family
ID=7786595
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP53054797A Expired - Fee Related JP4624497B2 (ja) | 1996-02-28 | 1997-02-15 | 置換されたカルボン酸タイプのアニオン非麻薬性鎮痛薬であるモルヒネ塩及びジアモルヒネ塩 |
Country Status (20)
Country | Link |
---|---|
US (1) | US6156764A (ja) |
EP (1) | EP0883619B1 (ja) |
JP (1) | JP4624497B2 (ja) |
KR (1) | KR100422276B1 (ja) |
CN (1) | CN1064363C (ja) |
AT (1) | ATE212024T1 (ja) |
AU (1) | AU712255B2 (ja) |
CZ (1) | CZ294401B6 (ja) |
DE (2) | DE19607395C2 (ja) |
DK (1) | DK0883619T3 (ja) |
ES (1) | ES2171886T3 (ja) |
HU (1) | HU225268B1 (ja) |
IL (1) | IL125819A (ja) |
NO (1) | NO983864L (ja) |
NZ (1) | NZ331485A (ja) |
PL (1) | PL185915B1 (ja) |
PT (1) | PT883619E (ja) |
SK (1) | SK104398A3 (ja) |
WO (1) | WO1997031918A1 (ja) |
ZA (1) | ZA971740B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007524628A (ja) * | 2003-06-26 | 2007-08-30 | シヴィダ・インコーポレイテッド | In−Situゲル化薬物輸送システム |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001517669A (ja) * | 1997-09-25 | 2001-10-09 | エルティエス ローマン テラピー−ズュステーメ アーゲー | モルヒネアルカロイド類の酸添加塩類およびその応用 |
EP1709957A3 (en) * | 2001-06-05 | 2007-02-14 | Control Delivery Systems | Sustained-release analgesic compounds |
EP1448190A2 (en) * | 2001-10-18 | 2004-08-25 | Novartis AG | Salts formed of an at1-receptor antagonist and a cardiovascular agent |
WO2003043657A1 (en) * | 2001-11-19 | 2003-05-30 | Control Delivery Systems, Inc. | Topical delivery of codrugs |
EP1465596A1 (en) * | 2002-01-18 | 2004-10-13 | Control Delivery Systems, Inc. | Polymeric gel system for the controlled delivery of codrugs |
US8557291B2 (en) * | 2002-07-05 | 2013-10-15 | Collegium Pharmaceutical, Inc. | Abuse-deterrent pharmaceutical compositions of opioids and other drugs |
WO2004004693A1 (en) | 2002-07-05 | 2004-01-15 | Collgegium Pharmaceutical | Abuse-deterrent pharmaceutical compositions of opiods and other drugs |
US10004729B2 (en) | 2002-07-05 | 2018-06-26 | Collegium Pharmaceutical, Inc. | Tamper-resistant pharmaceutical compositions of opioids and other drugs |
US8840928B2 (en) | 2002-07-05 | 2014-09-23 | Collegium Pharmaceutical, Inc. | Tamper-resistant pharmaceutical compositions of opioids and other drugs |
TW200500067A (en) * | 2003-01-21 | 2005-01-01 | Control Delivery Sys Inc | Salts of codrugs and uses related thereto |
US8815284B2 (en) * | 2003-06-26 | 2014-08-26 | Psivida Us, Inc. | Bioerodible sustained release drug delivery systems |
WO2005044236A1 (en) * | 2003-10-27 | 2005-05-19 | Control Delivery Systems, Inc. | Suspension delivery system for the sustained and controlled local release of pharmaceuticals |
LT1765292T (lt) * | 2004-06-12 | 2018-01-10 | Collegium Pharmaceutical, Inc. | Nuo piktnaudžiavimo apsaugotos vaistų formos |
US10668060B2 (en) | 2009-12-10 | 2020-06-02 | Collegium Pharmaceutical, Inc. | Tamper-resistant pharmaceutical compositions of opioids and other drugs |
WO2017222575A1 (en) | 2016-06-23 | 2017-12-28 | Collegium Pharmaceutical, Inc. | Process of making more stable abuse-deterrent oral formulations |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4404209A (en) * | 1982-06-30 | 1983-09-13 | E. I. Du Pont De Nemours And Company | Analgesic mixture of nalbuphine and sulindac |
GB8319546D0 (en) * | 1983-07-20 | 1983-08-24 | Euro Celtique Sa | Pharmaceutical active salts |
ZA893422B (en) * | 1988-02-24 | 1991-01-30 | Adcock Ingram Lab Ltd | Pharmaceutical composition |
TW225536B (ja) * | 1990-08-23 | 1994-06-21 | Ciba Geigy Ag | |
CA2104684A1 (en) * | 1991-03-04 | 1992-09-05 | Mahdi B. Fawzi | Salts/ion pairs of non-steroidal anti-inflammatory drugs in various dosage forms |
US5256669A (en) * | 1992-08-07 | 1993-10-26 | Aminotek Sciences, Inc. | Methods and compositions for treating acute or chronic pain and drug addiction |
SE9301057L (sv) * | 1993-03-30 | 1994-10-01 | Pharmacia Ab | Beredning med kontrollerad frisättning |
FR2708611B1 (fr) * | 1993-07-29 | 1995-10-27 | Meram Lab | Sel de codéine de l'acide 2-(3-benzoylphényl)propionique, procédé d'obtention et compositions pharmaceutiques le contenant. |
GB9319568D0 (en) * | 1993-09-22 | 1993-11-10 | Euro Celtique Sa | Pharmaceutical compositions and usages |
US5460826A (en) * | 1994-06-27 | 1995-10-24 | Alza Corporation | Morphine therapy |
-
1996
- 1996-02-28 DE DE19607395A patent/DE19607395C2/de not_active Expired - Fee Related
-
1997
- 1997-02-15 DK DK97903288T patent/DK0883619T3/da active
- 1997-02-15 IL IL12581997A patent/IL125819A/en not_active IP Right Cessation
- 1997-02-15 JP JP53054797A patent/JP4624497B2/ja not_active Expired - Fee Related
- 1997-02-15 AU AU17695/97A patent/AU712255B2/en not_active Ceased
- 1997-02-15 US US09/137,078 patent/US6156764A/en not_active Expired - Fee Related
- 1997-02-15 CZ CZ19982657A patent/CZ294401B6/cs not_active IP Right Cessation
- 1997-02-15 SK SK1043-98A patent/SK104398A3/sk unknown
- 1997-02-15 EP EP97903288A patent/EP0883619B1/de not_active Expired - Lifetime
- 1997-02-15 PT PT97903288T patent/PT883619E/pt unknown
- 1997-02-15 HU HU9900568A patent/HU225268B1/hu not_active IP Right Cessation
- 1997-02-15 AT AT97903288T patent/ATE212024T1/de active
- 1997-02-15 DE DE59706015T patent/DE59706015D1/de not_active Expired - Lifetime
- 1997-02-15 PL PL97328712A patent/PL185915B1/pl not_active IP Right Cessation
- 1997-02-15 KR KR10-1998-0706752A patent/KR100422276B1/ko not_active IP Right Cessation
- 1997-02-15 ES ES97903288T patent/ES2171886T3/es not_active Expired - Lifetime
- 1997-02-15 CN CN97192619A patent/CN1064363C/zh not_active Expired - Fee Related
- 1997-02-15 WO PCT/EP1997/000711 patent/WO1997031918A1/de active IP Right Grant
- 1997-02-15 NZ NZ331485A patent/NZ331485A/xx not_active IP Right Cessation
- 1997-02-27 ZA ZA9701740A patent/ZA971740B/xx unknown
-
1998
- 1998-08-21 NO NO983864A patent/NO983864L/no not_active Application Discontinuation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007524628A (ja) * | 2003-06-26 | 2007-08-30 | シヴィダ・インコーポレイテッド | In−Situゲル化薬物輸送システム |
Also Published As
Publication number | Publication date |
---|---|
SK104398A3 (en) | 1998-12-02 |
AU1769597A (en) | 1997-09-16 |
US6156764A (en) | 2000-12-05 |
JP4624497B2 (ja) | 2011-02-02 |
HUP9900568A2 (hu) | 1999-06-28 |
CN1064363C (zh) | 2001-04-11 |
HU225268B1 (en) | 2006-08-28 |
DK0883619T3 (da) | 2002-04-29 |
ZA971740B (en) | 1997-09-04 |
CZ265798A3 (cs) | 1998-11-11 |
PL328712A1 (en) | 1999-02-15 |
DE19607395A1 (de) | 1997-09-04 |
ATE212024T1 (de) | 2002-02-15 |
AU712255B2 (en) | 1999-11-04 |
WO1997031918A1 (de) | 1997-09-04 |
CN1212698A (zh) | 1999-03-31 |
KR19990087343A (ko) | 1999-12-27 |
PT883619E (pt) | 2002-07-31 |
IL125819A (en) | 2002-04-21 |
IL125819A0 (en) | 1999-04-11 |
NO983864D0 (no) | 1998-08-21 |
NO983864L (no) | 1998-08-21 |
DE19607395C2 (de) | 2002-11-21 |
DE59706015D1 (de) | 2002-02-21 |
EP0883619A1 (de) | 1998-12-16 |
NZ331485A (en) | 1999-03-29 |
HUP9900568A3 (en) | 2001-08-28 |
PL185915B1 (pl) | 2003-08-29 |
CZ294401B6 (cs) | 2004-12-15 |
KR100422276B1 (ko) | 2004-07-30 |
ES2171886T3 (es) | 2002-09-16 |
EP0883619B1 (de) | 2002-01-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4624497B2 (ja) | 置換されたカルボン酸タイプのアニオン非麻薬性鎮痛薬であるモルヒネ塩及びジアモルヒネ塩 | |
TWI686376B (zh) | 雙環化合物 | |
CN103533937A (zh) | 杂合阿片样化合物和组合物 | |
CA2781436C (en) | Arachidonic acid analogs and methods for analgesic treatment using same | |
JPS6341429A (ja) | セロトニンきっ抗物質の治療的用途 | |
CN112574098B (zh) | 一种酰胺化合物及其制备方法和用途 | |
EP0306345B1 (en) | 2-alkoxy-n-(1-azabicyclo(2.2.2)-oct-3-yl) benzamides and thiobenzamides having an antischizophrenic activity | |
TWI797127B (zh) | 止痛化合物 | |
CN111556748B (zh) | 一种局部麻醉药物 | |
JP2005511611A (ja) | インテグリン受容体拮抗薬のアミン塩 | |
JPH06271578A (ja) | 鎮痛剤ナルブフィン前薬の誘導体 | |
US2891890A (en) | Method of treating parkinsonism | |
CA2247616C (en) | Morphine and diamorphine salts of anionic non-narcotic analgesics of the substituted carboxylic acid type | |
CN112979572B (zh) | 一种帕瑞昔布衍生物及其制备方法和应用 | |
US9937262B2 (en) | Prodrugs of naproxen and diclofenac | |
JP3784868B2 (ja) | 医薬用水和物 | |
MXPA98006855A (en) | Salts of morphine and diamorphine of anionic analyzes, non-narcotics, of the type of carboxylic acids substituted, processes for their production, its application and the pharmaceutical preparations containing these sa | |
JPWO2010032731A1 (ja) | 結晶態様のベンゾイミダゾール化合物又はその塩 | |
US3092634A (en) | Novel [nitric acid ester] derivatives of nicotinic acid | |
WO2023205764A1 (en) | Opioid receptor agonist and methods of use thereof | |
IE45480B1 (en) | N-2,6-dichlorophenyl-2-aminopyrimidine and therapeutic compositions containing it | |
JPH05229942A (ja) | 消化管運動機能改善剤 | |
JPS62249934A (ja) | 外用製剤の製造方法 | |
JPH0827001A (ja) | 術後嘔吐の予防または治療薬 | |
JPH04208283A (ja) | 新規な複素環式化合物およびそれを含有する医薬組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070821 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071121 |
|
A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20071121 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20080219 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080616 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20080703 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20080717 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080716 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091005 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091016 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091104 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091113 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091202 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091211 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20101104 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131112 Year of fee payment: 3 |
|
LAPS | Cancellation because of no payment of annual fees |