HUE030963T2 - Sustained release formulations containing a 2-oxo-pyrrolidine derivative - Google Patents
Sustained release formulations containing a 2-oxo-pyrrolidine derivative Download PDFInfo
- Publication number
- HUE030963T2 HUE030963T2 HUE09752825A HUE09752825A HUE030963T2 HU E030963 T2 HUE030963 T2 HU E030963T2 HU E09752825 A HUE09752825 A HU E09752825A HU E09752825 A HUE09752825 A HU E09752825A HU E030963 T2 HUE030963 T2 HU E030963T2
- Authority
- HU
- Hungary
- Prior art keywords
- amely amely
- pharmaceutical composition
- controlled release
- agent
- layer
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title description 49
- 238000009472 formulation Methods 0.000 title description 8
- 230000002035 prolonged effect Effects 0.000 title description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title 1
- 229920001577 copolymer Polymers 0.000 claims description 20
- 229920000642 polymer Polymers 0.000 claims description 17
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 230000004044 response Effects 0.000 claims description 10
- 239000000049 pigment Substances 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 241000238876 Acari Species 0.000 claims 1
- 241000219991 Lythraceae Species 0.000 claims 1
- 235000014360 Punica granatum Nutrition 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 206010013932 dyslexia Diseases 0.000 claims 1
- 230000001926 lymphatic effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 description 79
- 239000010410 layer Substances 0.000 description 66
- 238000013270 controlled release Methods 0.000 description 56
- 239000003795 chemical substances by application Substances 0.000 description 52
- MSYKRHVOOPPJKU-BDAKNGLRSA-N brivaracetam Chemical compound CCC[C@H]1CN([C@@H](CC)C(N)=O)C(=O)C1 MSYKRHVOOPPJKU-BDAKNGLRSA-N 0.000 description 37
- 229960002161 brivaracetam Drugs 0.000 description 36
- 239000011230 binding agent Substances 0.000 description 29
- ANWPENAPCIFDSZ-RQJHMYQMSA-N Seletracetam Chemical compound CC[C@@H](C(N)=O)N1C[C@H](C=C(F)F)CC1=O ANWPENAPCIFDSZ-RQJHMYQMSA-N 0.000 description 21
- 229950000852 seletracetam Drugs 0.000 description 20
- 239000006057 Non-nutritive feed additive Substances 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 15
- 238000004090 dissolution Methods 0.000 description 14
- HPHUVLMMVZITSG-LURJTMIESA-N levetiracetam Chemical compound CC[C@@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-LURJTMIESA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 229960004002 levetiracetam Drugs 0.000 description 13
- 239000002245 particle Substances 0.000 description 13
- 239000003085 diluting agent Substances 0.000 description 12
- 239000000454 talc Substances 0.000 description 12
- 229910052623 talc Inorganic materials 0.000 description 12
- 235000012222 talc Nutrition 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 11
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 11
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 11
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 9
- 229920002472 Starch Polymers 0.000 description 9
- 239000008187 granular material Substances 0.000 description 9
- 235000019698 starch Nutrition 0.000 description 9
- 206010010904 Convulsion Diseases 0.000 description 8
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 230000010412 perfusion Effects 0.000 description 8
- 239000004014 plasticizer Substances 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 206010053398 Clonic convulsion Diseases 0.000 description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000001787 epileptiform Effects 0.000 description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 7
- 239000008108 microcrystalline cellulose Substances 0.000 description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 6
- 206010015037 epilepsy Diseases 0.000 description 6
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 235000010980 cellulose Nutrition 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000000763 evoking effect Effects 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 230000000971 hippocampal effect Effects 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 239000001856 Ethyl cellulose Substances 0.000 description 4
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 4
- 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 4
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000001961 anticonvulsive agent Substances 0.000 description 4
- 229920001249 ethyl cellulose Polymers 0.000 description 4
- 235000019325 ethyl cellulose Nutrition 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 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 4
- HKJKCPKPSSVUHY-GRTNUQQKSA-M (6r)-6-[(5s)-6,6-dimethyl-7,8-dihydro-5h-[1,3]dioxolo[4,5-g]isoquinolin-6-ium-5-yl]-6h-furo[3,4-g][1,3]benzodioxol-8-one;iodide Chemical compound [I-].O([C@H]1[C@@H]2C3=CC=4OCOC=4C=C3CC[N+]2(C)C)C(=O)C2=C1C=CC1=C2OCO1 HKJKCPKPSSVUHY-GRTNUQQKSA-M 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 3
- 208000024255 Audiogenic seizures Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 230000001773 anti-convulsant effect Effects 0.000 description 3
- 229960003965 antiepileptics Drugs 0.000 description 3
- 239000002518 antifoaming agent Substances 0.000 description 3
- 229920002301 cellulose acetate Polymers 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
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000008119 colloidal silica Substances 0.000 description 3
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 3
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000000391 magnesium silicate Substances 0.000 description 3
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 3
- 235000019793 magnesium trisilicate Nutrition 0.000 description 3
- 229940099273 magnesium trisilicate Drugs 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 229940033134 talc Drugs 0.000 description 3
- 235000019731 tricalcium phosphate Nutrition 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 229910002016 Aerosil® 200 Inorganic materials 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
- IYGYMKDQCDOMRE-QRWMCTBCSA-N Bicculine Chemical compound O([C@H]1C2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-QRWMCTBCSA-N 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- 229920003163 Eudragit® NE 30 D Polymers 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 2
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 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
- 206010043994 Tonic convulsion Diseases 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- AACMFFIUYXGCOC-UHFFFAOYSA-N bicuculline Natural products CN1CCc2cc3OCOc3cc2C1C4OCc5c6OCOc6ccc45 AACMFFIUYXGCOC-UHFFFAOYSA-N 0.000 description 2
- 230000009172 bursting Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- IYGYMKDQCDOMRE-UHFFFAOYSA-N d-Bicucullin Natural products CN1CCC2=CC=3OCOC=3C=C2C1C1OC(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 201000006517 essential tremor Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000006068 taste-masking agent Substances 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000022497 Cocaine-Related disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 229920003151 Eudragit® RL polymer Polymers 0.000 description 1
- 229920003152 Eudragit® RS polymer Polymers 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000021966 Motor seizure Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- 206010061533 Myotonia Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 229920001100 Polydextrose Polymers 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- 208000005793 Restless legs syndrome Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 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
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 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
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000002566 clonic effect Effects 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 201000001272 cocaine abuse Diseases 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000002920 convulsive effect Effects 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000008579 epileptogenesis Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000001535 kindling effect Effects 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- -1 orsucrose Polymers 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 150000002939 palatinoses Chemical class 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000001259 polydextrose Substances 0.000 description 1
- 235000013856 polydextrose Nutrition 0.000 description 1
- 229940035035 polydextrose Drugs 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000009183 running Effects 0.000 description 1
- 229940083037 simethicone Drugs 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
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 230000001256 tonic effect Effects 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4891—Coated capsules; Multilayered drug free capsule shells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Rheumatology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08105817 | 2008-11-18 | ||
| EP09100311 | 2009-06-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HUE030963T2 true HUE030963T2 (en) | 2017-06-28 |
Family
ID=41395028
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HUE09752825A HUE030963T2 (en) | 2008-11-18 | 2009-11-17 | Sustained release formulations containing a 2-oxo-pyrrolidine derivative |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US8460712B2 (enExample) |
| EP (1) | EP2358361B1 (enExample) |
| JP (2) | JP5954889B2 (enExample) |
| KR (2) | KR101788804B1 (enExample) |
| CN (2) | CN104083341A (enExample) |
| AU (1) | AU2009317279B2 (enExample) |
| BR (1) | BRPI0921301A2 (enExample) |
| CA (1) | CA2741038C (enExample) |
| DK (1) | DK2358361T3 (enExample) |
| EA (1) | EA019583B1 (enExample) |
| ES (1) | ES2602606T3 (enExample) |
| HK (1) | HK1198288A1 (enExample) |
| HU (1) | HUE030963T2 (enExample) |
| IL (1) | IL212271A (enExample) |
| MX (1) | MX356281B (enExample) |
| PL (1) | PL2358361T3 (enExample) |
| PT (1) | PT2358361T (enExample) |
| WO (1) | WO2010057869A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2358360T3 (pl) * | 2008-11-18 | 2017-02-28 | Ucb Biopharma Sprl | Preparaty o przedłużonym uwalnianiu zawierające pochodną 2-okso-1-pirolidyny |
| JP6902033B2 (ja) | 2015-12-30 | 2021-07-14 | アダマス ファーマシューティカルズ， インコーポレイテッド | 発作−関連障害の処置のための方法および組成物 |
| WO2017195144A1 (en) * | 2016-05-12 | 2017-11-16 | Jubilant Generics Limited | Pharmaceutical compositions comprising brivaracetam |
| CA3216586A1 (en) * | 2021-05-11 | 2022-11-17 | Caroline Roussel-Maupetit | Prolonged-release pharmaceutical composition for oral administration of sultiame |
| CN115721624A (zh) * | 2021-08-25 | 2023-03-03 | 北京海美源医药科技有限公司 | 一种布立西坦药物组合物及其制备方法和其应用 |
| WO2025128057A1 (en) * | 2023-12-13 | 2025-06-19 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A sachet formulation comprising brivaracetam |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0004297D0 (en) * | 2000-02-23 | 2000-04-12 | Ucb Sa | 2-oxo-1 pyrrolidine derivatives process for preparing them and their uses |
| NZ556630A (en) | 2005-01-27 | 2010-12-24 | Alembic Ltd | Extended release formulation of levetiracetam including a hydrophilic rate controlling polymer |
| US20070298098A1 (en) * | 2005-02-16 | 2007-12-27 | Elan Pharma International Limited | Controlled Release Compositions Comprising Levetiracetam |
| WO2006088864A1 (en) * | 2005-02-16 | 2006-08-24 | Elan Pharma International Limited | Controlled release compositions comprising levetiracetam |
| US8431156B2 (en) | 2005-02-22 | 2013-04-30 | Sun Pharma Advanced Research Company Ltd. | Pharmaceutical composition |
| EP1863453A2 (en) * | 2005-03-29 | 2007-12-12 | Evonik Röhm GmbH | Multiparticulate pharmaceutical form comprising pellets with a substance having a modular effect in relation to active ingredient release |
| FR2897267A1 (fr) * | 2006-02-16 | 2007-08-17 | Flamel Technologies Sa | Formes pharmaceutiques multimicroparticulaires pour administration per os |
| CN101506157B (zh) * | 2006-06-08 | 2013-07-24 | Ucb医药有限公司 | 吡咯烷酮共结晶 |
| KR101468053B1 (ko) * | 2006-08-31 | 2014-12-02 | 앱탈리스 파마테크, 인코포레이티드 | 약 염기성 약물의 고용체를 포함하는 약물 전달 시스템 |
| WO2008062446A2 (en) | 2006-09-14 | 2008-05-29 | Alembic Limited | An extended release composition of levetiracetam, which exhibits no adverse food effect |
| PL2187875T3 (pl) * | 2007-09-21 | 2013-01-31 | Evonik Roehm Gmbh | Kompozycja farmaceutyczna o zależnym od pH kontrolowanym uwalnianiu dla nieopioidów z odpornością przed wpływem etanolu |
| PT2273975E (pt) | 2008-03-03 | 2014-07-17 | Ucb Pharma Sa | Processos de preparação e utilizações terapêuticas de soluções farmacêuticas |
-
2009
- 2009-11-17 EA EA201100753A patent/EA019583B1/ru unknown
- 2009-11-17 AU AU2009317279A patent/AU2009317279B2/en active Active
- 2009-11-17 MX MX2011004572A patent/MX356281B/es active IP Right Grant
- 2009-11-17 PL PL09752825T patent/PL2358361T3/pl unknown
- 2009-11-17 HU HUE09752825A patent/HUE030963T2/en unknown
- 2009-11-17 KR KR1020177000418A patent/KR101788804B1/ko active Active
- 2009-11-17 BR BRPI0921301A patent/BRPI0921301A2/pt not_active IP Right Cessation
- 2009-11-17 JP JP2011543762A patent/JP5954889B2/ja active Active
- 2009-11-17 CA CA2741038A patent/CA2741038C/en active Active
- 2009-11-17 KR KR1020117014019A patent/KR20110089184A/ko not_active Ceased
- 2009-11-17 DK DK09752825.1T patent/DK2358361T3/en active
- 2009-11-17 CN CN201410370727.9A patent/CN104083341A/zh active Pending
- 2009-11-17 CN CN2009801455887A patent/CN102215828A/zh active Pending
- 2009-11-17 US US13/128,950 patent/US8460712B2/en active Active
- 2009-11-17 EP EP09752825.1A patent/EP2358361B1/en active Active
- 2009-11-17 ES ES09752825.1T patent/ES2602606T3/es active Active
- 2009-11-17 WO PCT/EP2009/065270 patent/WO2010057869A1/en not_active Ceased
- 2009-11-17 PT PT97528251T patent/PT2358361T/pt unknown
-
2011
- 2011-04-12 IL IL212271A patent/IL212271A/en active IP Right Grant
-
2014
- 2014-11-21 HK HK14111805.6A patent/HK1198288A1/xx unknown
-
2015
- 2015-03-31 JP JP2015071166A patent/JP2015143256A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DK2358361T3 (en) | 2016-12-12 |
| PT2358361T (pt) | 2016-11-18 |
| PL2358361T3 (pl) | 2017-02-28 |
| KR20170007528A (ko) | 2017-01-18 |
| AU2009317279B2 (en) | 2013-10-24 |
| AU2009317279A1 (en) | 2010-05-27 |
| JP2015143256A (ja) | 2015-08-06 |
| CN102215828A (zh) | 2011-10-12 |
| CA2741038A1 (en) | 2010-05-27 |
| KR20110089184A (ko) | 2011-08-04 |
| EA201100753A1 (ru) | 2012-01-30 |
| CA2741038C (en) | 2015-01-13 |
| WO2010057869A1 (en) | 2010-05-27 |
| EP2358361B1 (en) | 2016-09-14 |
| JP5954889B2 (ja) | 2016-07-20 |
| BRPI0921301A2 (pt) | 2015-12-29 |
| CN104083341A (zh) | 2014-10-08 |
| MX2011004572A (es) | 2011-06-17 |
| US8460712B2 (en) | 2013-06-11 |
| US20110274762A1 (en) | 2011-11-10 |
| EA019583B1 (ru) | 2014-04-30 |
| JP2012509356A (ja) | 2012-04-19 |
| HK1198288A1 (en) | 2015-03-27 |
| IL212271A0 (en) | 2011-06-30 |
| EP2358361A1 (en) | 2011-08-24 |
| MX356281B (es) | 2018-05-22 |
| ES2602606T3 (es) | 2017-02-21 |
| KR101788804B1 (ko) | 2017-10-20 |
| IL212271A (en) | 2016-10-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2358360T3 (en) | EXTENDED release formulations comprising one 2-OXO-1 PYRROLIDIN DERIVATIVE | |
| EP2393483B1 (en) | Pharmaceutical compositions comprising brivaracetam | |
| KR20090029830A (ko) | 소장 내에서 활성성분의 방출이 제어되는 경구투여용 약제학적 조제물 및 그의 제조방법 | |
| AU2006206423A1 (en) | Pharmaceutical formulations and methods of use | |
| HUE030963T2 (en) | Sustained release formulations containing a 2-oxo-pyrrolidine derivative | |
| HUE028579T2 (en) | New combination | |
| HK1159503B (en) | Prolonged release formulations comprising an 2-oxo-1-pyrrolidine derivative | |
| HK1159502A (en) | Prolonged release formulations comprising an 2-oxo-1-pyrrolidine derivate |