MX2012009821A - Formas cristalinas de la sal de tri-mesilato de perfenazina-gaba y proceso para producirlas. - Google Patents
Formas cristalinas de la sal de tri-mesilato de perfenazina-gaba y proceso para producirlas.Info
- Publication number
- MX2012009821A MX2012009821A MX2012009821A MX2012009821A MX2012009821A MX 2012009821 A MX2012009821 A MX 2012009821A MX 2012009821 A MX2012009821 A MX 2012009821A MX 2012009821 A MX2012009821 A MX 2012009821A MX 2012009821 A MX2012009821 A MX 2012009821A
- Authority
- MX
- Mexico
- Prior art keywords
- perphenazine
- aminobutyrate
- trimesylate
- crystalline form
- xrpd
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 66
- 230000008569 process Effects 0.000 title claims abstract description 31
- BABFYCSPNDKXRI-UHFFFAOYSA-N 2-[4-[3-(2-chlorophenothiazin-10-yl)propyl]piperazin-1-yl]ethyl 4-aminobutanoate Chemical compound C1CN(CCOC(=O)CCCN)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 BABFYCSPNDKXRI-UHFFFAOYSA-N 0.000 claims abstract description 63
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 59
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 174
- RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 claims description 103
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 103
- 229960000762 perphenazine Drugs 0.000 claims description 103
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 85
- 239000000203 mixture Substances 0.000 claims description 46
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 41
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 36
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 36
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 32
- 238000002441 X-ray diffraction Methods 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 22
- 230000001747 exhibiting effect Effects 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 18
- 208000035475 disorder Diseases 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 208000015114 central nervous system disease Diseases 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000005022 packaging material Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 230000003920 cognitive function Effects 0.000 claims description 2
- 238000007639 printing Methods 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 10
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 238000010511 deprotection reaction Methods 0.000 abstract description 4
- 238000011065 in-situ storage Methods 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 150000003839 salts Chemical class 0.000 description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- 239000007787 solid Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- 239000000047 product Substances 0.000 description 26
- 239000002245 particle Substances 0.000 description 23
- 238000005259 measurement Methods 0.000 description 22
- 238000004128 high performance liquid chromatography Methods 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 18
- 239000000523 sample Substances 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 208000010877 cognitive disease Diseases 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 239000000463 material Substances 0.000 description 11
- 210000003169 central nervous system Anatomy 0.000 description 10
- 239000013557 residual solvent Substances 0.000 description 10
- 238000001035 drying Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000009102 absorption Effects 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 238000000386 microscopy Methods 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 208000026139 Memory disease Diseases 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000004190 ion pair chromatography Methods 0.000 description 6
- 238000010926 purge Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 238000003795 desorption Methods 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 238000004448 titration Methods 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 208000028698 Cognitive impairment Diseases 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000008033 biological extinction Effects 0.000 description 4
- 208000029028 brain injury Diseases 0.000 description 4
- 208000037765 diseases and disorders Diseases 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 238000004255 ion exchange chromatography Methods 0.000 description 4
- 206010027175 memory impairment Diseases 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 229940001470 psychoactive drug Drugs 0.000 description 4
- 239000004089 psychotropic agent Substances 0.000 description 4
- 239000012265 solid product Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000005054 agglomeration Methods 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- -1 t-butoxycarbonyl Chemical group 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- 208000000044 Amnesia Diseases 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
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 2
- 101100054570 Caenorhabditis elegans acn-1 gene Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 2
- 229910002483 Cu Ka Inorganic materials 0.000 description 2
- 208000001640 Fibromyalgia Diseases 0.000 description 2
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 2
- 208000019022 Mood disease Diseases 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000001387 anti-histamine Effects 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000004067 bulking agent Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 230000006999 cognitive decline Effects 0.000 description 2
- 239000006059 cover glass Substances 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000006984 memory degeneration Effects 0.000 description 2
- 208000023060 memory loss Diseases 0.000 description 2
- 208000027061 mild cognitive impairment Diseases 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 238000003921 particle size analysis Methods 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000001907 polarising light microscopy Methods 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- QWCKQJZIFLGMSD-UHFFFAOYSA-N 2-Aminobutanoic acid Natural products CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 1
- 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 1
- HIDJWBGOQFTDLU-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC(O)=O HIDJWBGOQFTDLU-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 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 1
- QWCKQJZIFLGMSD-GSVOUGTGSA-N D-alpha-aminobutyric acid Chemical compound CC[C@@H](N)C(O)=O QWCKQJZIFLGMSD-GSVOUGTGSA-N 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 238000003109 Karl Fischer titration Methods 0.000 description 1
- 241000407429 Maja Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- OPTFQOKKHIRKDH-UHFFFAOYSA-N acetonitrile;butyl acetate Chemical compound CC#N.CCCCOC(C)=O OPTFQOKKHIRKDH-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229940067621 aminobutyrate Drugs 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 231100000871 behavioral problem Toxicity 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 208000030963 borderline personality disease Diseases 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 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
- 238000011088 calibration curve Methods 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 231100000870 cognitive problem Toxicity 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 239000012457 nonaqueous media Substances 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
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000007415 particle size distribution analysis Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 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
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/18—[b, e]-condensed with two six-membered rings
- C07D279/22—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom
- C07D279/24—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom
- C07D279/28—[b, e]-condensed with two six-membered rings with carbon atoms directly attached to the ring nitrogen atom with hydrocarbon radicals, substituted by amino radicals, attached to the ring nitrogen atom with other substituents attached to the ring system
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30748210P | 2010-02-24 | 2010-02-24 | |
| US30748110P | 2010-02-24 | 2010-02-24 | |
| PCT/IB2011/000915 WO2011104637A2 (en) | 2010-02-24 | 2011-02-24 | Crystalline forms of the tri-mesylate salt of perphenazine-gaba and process of producing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2012009821A true MX2012009821A (es) | 2012-10-09 |
Family
ID=44507308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2012009821A MX2012009821A (es) | 2010-02-24 | 2011-02-24 | Formas cristalinas de la sal de tri-mesilato de perfenazina-gaba y proceso para producirlas. |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US8377929B2 (https=) |
| EP (1) | EP2539857A4 (https=) |
| JP (1) | JP2013520488A (https=) |
| CN (1) | CN102858345A (https=) |
| AU (1) | AU2011219529A1 (https=) |
| CA (1) | CA2789654A1 (https=) |
| IL (1) | IL221461A0 (https=) |
| MX (1) | MX2012009821A (https=) |
| WO (1) | WO2011104637A2 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7544681B2 (en) * | 2001-09-27 | 2009-06-09 | Ramot At Tel Aviv University Ltd. | Conjugated psychotropic drugs and uses thereof |
| JP5284779B2 (ja) * | 2005-06-07 | 2013-09-11 | ラモット・アット・テル・アビブ・ユニバーシテイ・リミテッド | コンジュゲート化された向精神薬の新規な塩およびその調製方法 |
| EP2051735B1 (en) | 2006-07-17 | 2012-08-29 | Ramot, at Tel Aviv University Ltd. | Conjugates comprising a psychotropic drug or a gaba agonist and an organic acid and their use treating pain and other cns disorders |
| WO2009101616A1 (en) | 2008-02-11 | 2009-08-20 | Ramot At Tel Aviv University Ltd. | Novel conjugates for treating neurodegenerative diseases and disorders |
| WO2011070579A1 (en) * | 2009-12-09 | 2011-06-16 | Biolinerx Ltd. | Methods of improving cognitive functions |
| US8377929B2 (en) | 2010-02-24 | 2013-02-19 | Ramot At Tel-Aviv University Ltd. | Crystalline forms of the tri-mesylate salt of perphenazine-GABA and process of producing the same |
| WO2012038963A1 (en) | 2010-09-22 | 2012-03-29 | Ramot At Tel-Aviv University Ltd. | An acid addition salt of a nortriptyline-gaba conjugate and a process of preparing same |
| US10562930B1 (en) * | 2018-08-31 | 2020-02-18 | Praxis Precision Medicines, Inc. | Salts and crystal forms of GABAA positive allosteric modulator |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1460713A (en) | 1973-06-08 | 1977-01-06 | Kefalas As | 7-fluoro substituted phenothiazines method for preparation thereof and compositions bladed rotor for a gas turbine engine |
| US5525727A (en) | 1982-05-18 | 1996-06-11 | University Of Florida | Brain-specific drug delivery |
| GB8608335D0 (en) | 1986-04-04 | 1986-05-08 | Pfizer Ltd | Pharmaceutically acceptable salts |
| US5145684A (en) * | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| US5780590A (en) | 1993-10-15 | 1998-07-14 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Antithrombotic azacycloalkylalkanoyl peptides and pseudopeptides |
| US5534522A (en) | 1995-06-07 | 1996-07-09 | Warner-Lambert Company | (R)-(Z)-1-azabicyclo [2.2.1] heptan-3-one,O-[3-(3-methoxyphenyl)-2-propynyl] oxime maleate as a pharmaceutical agent |
| US5952365A (en) | 1995-07-13 | 1999-09-14 | Anormed Inc. | 2- 2-(Dimethylamino)ethyl!-8,8-dipropyl-2-azaspiro 4.5!decane dimaleate |
| DE19622489A1 (de) | 1996-06-05 | 1997-12-11 | Hoechst Ag | Salze des 3-(2-(4-(4-(Amino-imino-methyl)-phenyl)-4- methyl-2,5-dioxo-imidazolidin-1-yl)-acetylamino)-3- phenyl-propionsäure-ethylesters |
| US6130221A (en) | 1997-03-05 | 2000-10-10 | Nymox Corporation | Pharmaceutical agents that impede the initiation and progression of primary and secondary DMS disruptions |
| CA2475026A1 (en) | 1999-12-01 | 2001-06-07 | Ucb, S.A. | A pyrrolidineacetamide derivative alone or in combination for treatment of cns disorders |
| JP2005097120A (ja) | 2000-10-06 | 2005-04-14 | Mochida Pharmaceut Co Ltd | ４−ヒドロキシピペリジン誘導体の非潮解性塩 |
| US7544681B2 (en) * | 2001-09-27 | 2009-06-09 | Ramot At Tel Aviv University Ltd. | Conjugated psychotropic drugs and uses thereof |
| JP4521187B2 (ja) | 2001-09-27 | 2010-08-11 | ラモト アット テル アヴィヴ ユニヴァーシティ リミテッド | コンジュゲートされた抗精神病薬およびこれらの使用 |
| US7005138B2 (en) | 2001-12-21 | 2006-02-28 | Duramed Pharmaceuticals, Inc. | Method of systematically delivering SSRIs |
| US20040092504A1 (en) | 2002-11-12 | 2004-05-13 | Anuthep Benja-Athon | Definitive medications for treating fibromyalgia |
| TW200616604A (en) | 2004-08-26 | 2006-06-01 | Nicholas Piramal India Ltd | Nitric oxide releasing prodrugs containing bio-cleavable linker |
| JP5284779B2 (ja) * | 2005-06-07 | 2013-09-11 | ラモット・アット・テル・アビブ・ユニバーシテイ・リミテッド | コンジュゲート化された向精神薬の新規な塩およびその調製方法 |
| EP2272537A3 (en) * | 2005-06-07 | 2014-10-22 | Ramot at Tel-Aviv University Ltd. | Salts of conjugated psychotropic drugs and processes of preparing same |
| TWI378091B (en) | 2006-03-09 | 2012-12-01 | Eisai R&D Man Co Ltd | Multi-cyclic cinnamide derivatives |
| EP2250148B1 (en) | 2008-01-25 | 2016-08-17 | XenoPort, Inc. | Crystalline form of calcium-salts of (3s)-aminomethyl-5-methyl-hexanoic acids and methods of use |
| US8377929B2 (en) | 2010-02-24 | 2013-02-19 | Ramot At Tel-Aviv University Ltd. | Crystalline forms of the tri-mesylate salt of perphenazine-GABA and process of producing the same |
| WO2012038963A1 (en) | 2010-09-22 | 2012-03-29 | Ramot At Tel-Aviv University Ltd. | An acid addition salt of a nortriptyline-gaba conjugate and a process of preparing same |
-
2011
- 2011-02-24 US US13/034,453 patent/US8377929B2/en not_active Expired - Fee Related
- 2011-02-24 JP JP2012554446A patent/JP2013520488A/ja active Pending
- 2011-02-24 EP EP11746937.9A patent/EP2539857A4/en not_active Withdrawn
- 2011-02-24 CN CN2011800207232A patent/CN102858345A/zh active Pending
- 2011-02-24 MX MX2012009821A patent/MX2012009821A/es not_active Application Discontinuation
- 2011-02-24 AU AU2011219529A patent/AU2011219529A1/en not_active Abandoned
- 2011-02-24 WO PCT/IB2011/000915 patent/WO2011104637A2/en not_active Ceased
- 2011-02-24 CA CA2789654A patent/CA2789654A1/en not_active Abandoned
-
2012
- 2012-08-14 IL IL221461A patent/IL221461A0/en unknown
-
2013
- 2013-02-11 US US13/763,815 patent/US20130150352A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2789654A1 (en) | 2011-09-01 |
| IL221461A0 (en) | 2012-10-31 |
| WO2011104637A2 (en) | 2011-09-01 |
| EP2539857A4 (en) | 2013-07-24 |
| AU2011219529A1 (en) | 2012-08-30 |
| US20130150352A1 (en) | 2013-06-13 |
| US20110312948A1 (en) | 2011-12-22 |
| CN102858345A (zh) | 2013-01-02 |
| WO2011104637A3 (en) | 2012-02-23 |
| WO2011104637A9 (en) | 2012-01-05 |
| US8377929B2 (en) | 2013-02-19 |
| JP2013520488A (ja) | 2013-06-06 |
| EP2539857A2 (en) | 2013-01-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MX2012009821A (es) | Formas cristalinas de la sal de tri-mesilato de perfenazina-gaba y proceso para producirlas. | |
| US11566000B2 (en) | Crystalline form of sofpironium bromide and preparation method thereof | |
| US8916610B2 (en) | Acid addition salt of a nortriptyline-GABA conjugate and a process of preparing same | |
| IL291855A (en) | Solid forms of [(1s)-1-[(2s,4r,5r)-5-(5-amino-2-oxo-thiazolo[5,4-d]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran -2-yl]propyl]acetate | |
| AU2009309575B2 (en) | Choline and tromethamine salt of Licofelone | |
| US9694004B2 (en) | Crystal form | |
| US11643415B1 (en) | Rabeximod compounds | |
| CA2469225C (en) | Citric acid salt of 4-(3,4-dichlorophenyl)-2-[2-(4-methylpiperazin-1-yl)-benzylidene]-thiomorpholin-3-one and pharmaceutical compositions thereof | |
| US8729130B2 (en) | Methods of using novel solid forms of tacedinaline | |
| WO2012003413A1 (en) | Novel solid forms of tacedinaline | |
| HK40068368B (zh) | 索吡溴铵的晶型及其制备方法 | |
| US20130131023A1 (en) | New polymorphic form of a calcimimetic compound | |
| CN115636832A (zh) | 嘧啶并吡咯类化合物的可药用盐、晶型及其制备方法 | |
| WO2026086860A1 (zh) | At2受体抑制剂的盐、其固体形式及其制备方法和用途 | |
| HK1198534B (en) | Novel crystal form |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA | Abandonment or withdrawal |