TWI492937B - 噻萘普汀硫酸鹽型式及其製造及使用的方法 - Google Patents
噻萘普汀硫酸鹽型式及其製造及使用的方法 Download PDFInfo
- Publication number
- TWI492937B TWI492937B TW098136937A TW98136937A TWI492937B TW I492937 B TWI492937 B TW I492937B TW 098136937 A TW098136937 A TW 098136937A TW 98136937 A TW98136937 A TW 98136937A TW I492937 B TWI492937 B TW I492937B
- Authority
- TW
- Taiwan
- Prior art keywords
- tianeptine
- monohydrate
- hemisulfate
- methyldibenzo
- chloro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 72
- 229960005138 tianeptine Drugs 0.000 title description 402
- JICJBGPOMZQUBB-UHFFFAOYSA-N 7-[(3-chloro-6-methyl-5,5-dioxido-6,11-dihydrodibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid Chemical compound O=S1(=O)N(C)C2=CC=CC=C2C(NCCCCCCC(O)=O)C2=CC=C(Cl)C=C21 JICJBGPOMZQUBB-UHFFFAOYSA-N 0.000 claims description 344
- -1 3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepine-11-yl Chemical group 0.000 claims description 99
- 239000008194 pharmaceutical composition Substances 0.000 claims description 80
- 239000000203 mixture Substances 0.000 claims description 71
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 58
- 238000013270 controlled release Methods 0.000 claims description 57
- 241000124008 Mammalia Species 0.000 claims description 47
- 239000003826 tablet Substances 0.000 claims description 40
- 239000003814 drug Substances 0.000 claims description 39
- 239000002904 solvent Substances 0.000 claims description 34
- VCSZKSHWUBFOOE-UHFFFAOYSA-N dioxidanium;sulfate Chemical compound O.O.OS(O)(=O)=O VCSZKSHWUBFOOE-UHFFFAOYSA-N 0.000 claims description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 30
- 239000007937 lozenge Substances 0.000 claims description 28
- 238000004458 analytical method Methods 0.000 claims description 26
- 230000036470 plasma concentration Effects 0.000 claims description 25
- 150000001875 compounds Chemical class 0.000 claims description 20
- 159000000000 sodium salts Chemical class 0.000 claims description 20
- 239000013078 crystal Substances 0.000 claims description 18
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 14
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 14
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 14
- 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 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 238000001179 sorption measurement Methods 0.000 claims description 13
- 150000001412 amines Chemical class 0.000 claims description 10
- 229920000642 polymer Polymers 0.000 claims description 10
- 239000011541 reaction mixture Substances 0.000 claims description 5
- HLKOWEUTUIOPFA-UHFFFAOYSA-N 3-chloro-6-methyl-11H-benzo[c][2,1]benzothiazepine Chemical compound ClC1=CC2=C(CC3=C(N(S2)C)C=CC=C3)C=C1 HLKOWEUTUIOPFA-UHFFFAOYSA-N 0.000 claims description 4
- ZTHVLZXTYSAELD-UHFFFAOYSA-N 7-[(3-chloro-6-methyl-11h-benzo[c][2,1]benzothiazepin-11-yl)amino]heptanoic acid Chemical compound CN1SC2=CC(Cl)=CC=C2C(NCCCCCCC(O)=O)C2=CC=CC=C12 ZTHVLZXTYSAELD-UHFFFAOYSA-N 0.000 claims description 4
- 239000012530 fluid Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000007704 transition Effects 0.000 claims description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims 40
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000013067 intermediate product Substances 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 103
- 229910019142 PO4 Inorganic materials 0.000 description 97
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 97
- 239000010452 phosphate Substances 0.000 description 97
- VALUNVMGXVWSGM-UHFFFAOYSA-N 7-[(3-chloro-6-methyl-5,5-dioxo-11H-benzo[c][2,1]benzothiazepin-11-yl)amino]heptanoic acid hydrochloride Chemical compound Cl.O=S1(=O)N(C)C2=CC=CC=C2C(NCCCCCCC(O)=O)C2=CC=C(Cl)C=C21 VALUNVMGXVWSGM-UHFFFAOYSA-N 0.000 description 79
- KVVMXNNJBVTOSX-UHFFFAOYSA-N 7-[(3-chloro-6-methyl-5,5-dioxo-11H-benzo[c][2,1]benzothiazepin-11-yl)amino]heptanoic acid sulfuric acid dihydrate Chemical compound O.O.OS(O)(=O)=O.O=S1(=O)N(C)C2=CC=CC=C2C(NCCCCCCC(O)=O)C2=CC=C(Cl)C=C21.O=S1(=O)N(C)C2=CC=CC=C2C(NCCCCCCC(O)=O)C2=CC=C(Cl)C=C21 KVVMXNNJBVTOSX-UHFFFAOYSA-N 0.000 description 43
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 36
- 238000009472 formulation Methods 0.000 description 35
- 229940079593 drug Drugs 0.000 description 33
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 29
- 239000002552 dosage form Substances 0.000 description 29
- 150000004682 monohydrates Chemical class 0.000 description 29
- 238000011282 treatment Methods 0.000 description 27
- 238000012360 testing method Methods 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- 241001465754 Metazoa Species 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000008186 active pharmaceutical agent Substances 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 238000002411 thermogravimetry Methods 0.000 description 17
- 239000012453 solvate Substances 0.000 description 16
- 239000012458 free base Substances 0.000 description 15
- 150000002500 ions Chemical class 0.000 description 15
- 238000004090 dissolution Methods 0.000 description 12
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
- 239000003981 vehicle Substances 0.000 description 12
- 238000002425 crystallisation Methods 0.000 description 11
- 230000008025 crystallization Effects 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 10
- 230000003204 osmotic effect Effects 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- AWQSAIIDOMEEOD-UHFFFAOYSA-N 5,5-Dimethyl-4-(3-oxobutyl)dihydro-2(3H)-furanone Chemical compound CC(=O)CCC1CC(=O)OC1(C)C AWQSAIIDOMEEOD-UHFFFAOYSA-N 0.000 description 8
- 239000011521 glass Substances 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 239000002504 physiological saline solution Substances 0.000 description 8
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 7
- 208000006673 asthma Diseases 0.000 description 7
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000006186 oral dosage form Substances 0.000 description 7
- 238000005303 weighing Methods 0.000 description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 6
- 239000000935 antidepressant agent Substances 0.000 description 6
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 150000001768 cations Chemical class 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 150000004677 hydrates Chemical class 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
- 229940005513 antidepressants Drugs 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 230000003111 delayed effect Effects 0.000 description 5
- 238000013461 design Methods 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 4
- 239000008203 oral pharmaceutical composition Substances 0.000 description 4
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000010926 purge Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000009182 swimming Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000001757 thermogravimetry curve Methods 0.000 description 4
- 208000020401 Depressive disease Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229920003091 Methocel™ Polymers 0.000 description 3
- PKCGGIXXMMAGJZ-UHFFFAOYSA-N O.S(=O)(=O)(O)O.S(=O)(=O)(O)O.S(=O)(=O)(O)O.S(=O)(=O)(O)O.S(=O)(=O)(O)O Chemical compound O.S(=O)(=O)(O)O.S(=O)(=O)(O)O.S(=O)(=O)(O)O.S(=O)(=O)(O)O.S(=O)(=O)(O)O PKCGGIXXMMAGJZ-UHFFFAOYSA-N 0.000 description 3
- 238000001069 Raman spectroscopy Methods 0.000 description 3
- 238000001237 Raman spectrum Methods 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 description 3
- 239000008297 liquid dosage form Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000004570 mortar (masonry) Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- ZLBSUOGMZDXYKE-UHFFFAOYSA-M sodium;7-[(3-chloro-6-methyl-5,5-dioxo-11h-benzo[c][2,1]benzothiazepin-11-yl)amino]heptanoate Chemical compound [Na+].O=S1(=O)N(C)C2=CC=CC=C2C(NCCCCCCC([O-])=O)C2=CC=C(Cl)C=C21 ZLBSUOGMZDXYKE-UHFFFAOYSA-M 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 239000008247 solid mixture Substances 0.000 description 3
- 238000000527 sonication Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 229910021653 sulphate ion Inorganic materials 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 239000007916 tablet composition Substances 0.000 description 3
- 239000006208 topical dosage form Substances 0.000 description 3
- 238000002211 ultraviolet spectrum Methods 0.000 description 3
- 0 CCCNNC#*C Chemical compound CCCNNC#*C 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 206010017999 Gastrointestinal pain Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 238000004847 absorption spectroscopy Methods 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000002788 crimping Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000012728 immediate-release (IR) tablet Substances 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000013563 matrix tablet Substances 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 229940126701 oral medication Drugs 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000010453 quartz Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- 206010006582 Bundle branch block right Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000008081 Intestinal Fistula Diseases 0.000 description 1
- 229920004011 Macrolon® Polymers 0.000 description 1
- 229920003094 Methocel™ K4M Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 238000011785 NMRI mouse Methods 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229920001131 Pulp (paper) Polymers 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical compound [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000005266 casting Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 238000007580 dry-mixing Methods 0.000 description 1
- 229940095107 e.s.p. Drugs 0.000 description 1
- 239000004495 emulsifiable concentrate Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 235000020650 eye health related herbal supplements Nutrition 0.000 description 1
- 235000020937 fasting conditions Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 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 description 1
- 238000009740 moulding (composite fabrication) Methods 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- TWHXWYVOWJCXSI-UHFFFAOYSA-N phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O TWHXWYVOWJCXSI-UHFFFAOYSA-N 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019195 vitamin supplement Nutrition 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11000908P | 2008-10-31 | 2008-10-31 | |
| US11000108P | 2008-10-31 | 2008-10-31 | |
| US11000608P | 2008-10-31 | 2008-10-31 | |
| US22834309P | 2009-07-24 | 2009-07-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201029981A TW201029981A (en) | 2010-08-16 |
| TWI492937B true TWI492937B (zh) | 2015-07-21 |
Family
ID=43447880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW098136937A TWI492937B (zh) | 2008-10-31 | 2009-10-30 | 噻萘普汀硫酸鹽型式及其製造及使用的方法 |
Country Status (4)
| Country | Link |
|---|---|
| AR (1) | AR075295A1 (ar) |
| JO (1) | JO2844B1 (ar) |
| TW (1) | TWI492937B (ar) |
| UY (1) | UY32216A (ar) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3758528A (en) * | 1970-03-13 | 1973-09-11 | Science Union & Cie | Tricyclic compounds |
| US6599896B1 (en) * | 1999-04-07 | 2003-07-29 | Les Laboratoires Servier | Use of tianeptine in the production of medicaments to treat neurodegenerative pathologies |
-
2009
- 2009-10-29 JO JO2009398A patent/JO2844B1/ar active
- 2009-10-30 AR ARP090104204 patent/AR075295A1/es unknown
- 2009-10-30 TW TW098136937A patent/TWI492937B/zh not_active IP Right Cessation
- 2009-10-30 UY UY32216A patent/UY32216A/es unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3758528A (en) * | 1970-03-13 | 1973-09-11 | Science Union & Cie | Tricyclic compounds |
| US6599896B1 (en) * | 1999-04-07 | 2003-07-29 | Les Laboratoires Servier | Use of tianeptine in the production of medicaments to treat neurodegenerative pathologies |
Also Published As
| Publication number | Publication date |
|---|---|
| JO2844B1 (ar) | 2014-09-15 |
| TW201029981A (en) | 2010-08-16 |
| AR075295A1 (es) | 2011-03-23 |
| UY32216A (es) | 2010-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1163231C (zh) | 用于口服的美洛西肯的盖伦制剂 | |
| EP2870163B1 (en) | Pharmaceutical compositions comprising rifaximin and amino acids, preparation method and use thereof | |
| ES2562843T3 (es) | Forma IV de clorhidrato de ivabradina | |
| RU2539590C2 (ru) | Кристаллические формы саксаглиптина | |
| TWI878810B (zh) | 製造及使用因多昔芬(endoxifen)之方法 | |
| CN1970547B (zh) | 非布司他的晶型及其制备方法 | |
| TW202235417A (zh) | 整合素抑制劑及其用途 | |
| CN107567444A (zh) | 用于治疗精神分裂症的包含2‑((1‑(2‑(4‑氟苯基)‑2‑氧代乙基)哌啶‑4‑基)甲基)异吲哚啉‑1‑酮的组合物 | |
| US8124640B2 (en) | Pharmaceutical composition based on idazoxan, salts, hydrates or polymorphs thereof | |
| BR112019012340A2 (pt) | sais cristalinos e polimorfos de um antagonista p2x3 | |
| US8198268B2 (en) | Tianeptine sulfate salt forms and methods of making and using the same | |
| TWI903066B (zh) | 包含1-(3-氰基-1-異丙基-吲哚-5-基)吡唑-4-羧酸之口服用複合調配物 | |
| JP6093707B2 (ja) | 化合物製剤 | |
| JP2024539726A (ja) | N-((1r,3s)-3-(4-アセチルピペラジン-1-イル)シクロヘキシル)-4-フルオロ-7-メチル-1h-インドール-2-カルボキサミドの結晶形態 | |
| TWI492937B (zh) | 噻萘普汀硫酸鹽型式及其製造及使用的方法 | |
| CN102453020A (zh) | 一种来那度胺的新晶型及其制备方法 | |
| CN103006648A (zh) | 一种马来酸左旋氨氯地平药物活性组合物及其制备方法 | |
| JP2026512051A (ja) | ベンズイミダゾール誘導体の塩 | |
| TWI436988B (zh) | 7-〔(3-氯-6,11-二氫-6-甲基二苯并〔c,f〕〔1,2〕噻氮呯-11-基)胺〕庚酸s,s二氧化物之多晶型及其製造與使用方法 | |
| WO2017000270A1 (zh) | 枸橼酸舍曲林的2种晶型及其制备方法 | |
| CN102093309B (zh) | 非布司他的晶型及其制备方法 | |
| BR112020010135A2 (pt) | formas polimórficas de maleato de trimebutina e método de usar as mesmas | |
| CN119462561B (zh) | 化合物的晶型及其制备方法、原料药、组合物和用途 | |
| CN106692067B (zh) | 双嘧达莫固体分散体、口崩片及其制备方法 | |
| JP7506475B2 (ja) | フェブキソスタット製剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |