CN112843005B - 左乙拉西坦的延时释放药物组合物 - Google Patents
左乙拉西坦的延时释放药物组合物 Download PDFInfo
- Publication number
- CN112843005B CN112843005B CN202011470929.2A CN202011470929A CN112843005B CN 112843005 B CN112843005 B CN 112843005B CN 202011470929 A CN202011470929 A CN 202011470929A CN 112843005 B CN112843005 B CN 112843005B
- Authority
- CN
- China
- Prior art keywords
- cognitive impairment
- pharmaceutical composition
- extended release
- levetiracetam
- release pharmaceutical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000013265 extended release Methods 0.000 title claims abstract description 207
- 229960004002 levetiracetam Drugs 0.000 title claims abstract description 157
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 148
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical group CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 title claims abstract 14
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 184
- 239000000203 mixture Substances 0.000 claims description 145
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 113
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 113
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 111
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 104
- 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 67
- 235000019359 magnesium stearate Nutrition 0.000 claims description 51
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 50
- 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 claims description 46
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 44
- 239000008119 colloidal silica Substances 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 26
- 229920000642 polymer Polymers 0.000 claims description 17
- 230000019771 cognition Effects 0.000 claims description 16
- 239000002552 dosage form Substances 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 235000019739 Dicalciumphosphate Nutrition 0.000 claims description 9
- 239000001506 calcium phosphate Substances 0.000 claims description 9
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 claims description 9
- 229940038472 dicalcium phosphate Drugs 0.000 claims description 9
- 229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 9
- 230000003111 delayed effect Effects 0.000 claims description 8
- 239000011248 coating agent Substances 0.000 claims description 4
- 238000000576 coating method Methods 0.000 claims description 4
- 230000002209 hydrophobic effect Effects 0.000 claims description 3
- 208000028698 Cognitive impairment Diseases 0.000 abstract description 127
- 238000000034 method Methods 0.000 abstract description 96
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 26
- 210000003169 central nervous system Anatomy 0.000 abstract description 24
- 238000002360 preparation method Methods 0.000 abstract description 3
- HPHUVLMMVZITSG-LURJTMIESA-N levetiracetam Chemical group CC[C@@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-LURJTMIESA-N 0.000 description 143
- 239000003826 tablet Substances 0.000 description 127
- 238000011282 treatment Methods 0.000 description 76
- 238000012360 testing method Methods 0.000 description 65
- 230000003920 cognitive function Effects 0.000 description 51
- 238000010171 animal model Methods 0.000 description 49
- 229960003943 hypromellose Drugs 0.000 description 44
- 206010012289 Dementia Diseases 0.000 description 41
- 229920003091 Methocel™ Polymers 0.000 description 41
- 201000000980 schizophrenia Diseases 0.000 description 41
- 241000700159 Rattus Species 0.000 description 39
- 208000028173 post-traumatic stress disease Diseases 0.000 description 36
- 241001465754 Metazoa Species 0.000 description 35
- 208000024891 symptom Diseases 0.000 description 34
- 208000018737 Parkinson disease Diseases 0.000 description 27
- 238000009472 formulation Methods 0.000 description 27
- 102220487426 Actin-related protein 2/3 complex subunit 3_K15M_mutation Human genes 0.000 description 26
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 26
- 208000036626 Mental retardation Diseases 0.000 description 25
- BELPJCDYWUCHKF-WAYWQWQTSA-N Methylazoxymethanol acetate Chemical compound CC(=O)OC\N=[N+](\C)[O-] BELPJCDYWUCHKF-WAYWQWQTSA-N 0.000 description 25
- 238000011275 oncology therapy Methods 0.000 description 25
- 208000024827 Alzheimer disease Diseases 0.000 description 24
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 24
- 230000001149 cognitive effect Effects 0.000 description 24
- 239000002775 capsule Substances 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- 230000000971 hippocampal effect Effects 0.000 description 21
- 208000030459 obsessive-compulsive personality disease Diseases 0.000 description 20
- 208000007656 osteochondritis dissecans Diseases 0.000 description 20
- 208000011117 substance-related disease Diseases 0.000 description 20
- 230000000694 effects Effects 0.000 description 19
- 241000282472 Canis lupus familiaris Species 0.000 description 18
- 241000282412 Homo Species 0.000 description 18
- 208000035475 disorder Diseases 0.000 description 18
- 230000015654 memory Effects 0.000 description 18
- 230000006399 behavior Effects 0.000 description 17
- 210000004556 brain Anatomy 0.000 description 17
- 229940079593 drug Drugs 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 206010003805 Autism Diseases 0.000 description 16
- 208000020706 Autistic disease Diseases 0.000 description 16
- 208000020925 Bipolar disease Diseases 0.000 description 16
- 230000002829 reductive effect Effects 0.000 description 15
- 206010026749 Mania Diseases 0.000 description 14
- 208000015114 central nervous system disease Diseases 0.000 description 13
- 230000002354 daily effect Effects 0.000 description 13
- 230000007423 decrease Effects 0.000 description 13
- 229960003638 dopamine Drugs 0.000 description 13
- 230000001771 impaired effect Effects 0.000 description 13
- 230000013016 learning Effects 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- 230000007000 age related cognitive decline Effects 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 10
- 230000003542 behavioural effect Effects 0.000 description 10
- 230000007278 cognition impairment Effects 0.000 description 10
- 230000006735 deficit Effects 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 230000004064 dysfunction Effects 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- 239000003085 diluting agent Substances 0.000 description 8
- 235000013305 food Nutrition 0.000 description 8
- 230000009246 food effect Effects 0.000 description 8
- 230000036470 plasma concentration Effects 0.000 description 8
- 208000020016 psychiatric disease Diseases 0.000 description 8
- 208000011580 syndromic disease Diseases 0.000 description 8
- 230000006999 cognitive decline Effects 0.000 description 7
- 231100000867 compulsive behavior Toxicity 0.000 description 7
- 238000013461 design Methods 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 230000008030 elimination Effects 0.000 description 7
- 238000003379 elimination reaction Methods 0.000 description 7
- 235000021471 food effect Nutrition 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 238000007619 statistical method Methods 0.000 description 7
- 208000001914 Fragile X syndrome Diseases 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 208000028017 Psychotic disease Diseases 0.000 description 6
- 239000000599 controlled substance Substances 0.000 description 6
- 238000002599 functional magnetic resonance imaging Methods 0.000 description 6
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 6
- 239000000314 lubricant Substances 0.000 description 6
- 208000007848 Alcoholism Diseases 0.000 description 5
- 238000012347 Morris Water Maze Methods 0.000 description 5
- 230000032683 aging Effects 0.000 description 5
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 5
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 5
- 229960004046 apomorphine Drugs 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 5
- 230000007850 degeneration Effects 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 206010027175 memory impairment Diseases 0.000 description 5
- 230000003340 mental effect Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000006886 spatial memory Effects 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 238000012549 training Methods 0.000 description 5
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 4
- 201000010374 Down Syndrome Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 102100023532 Synaptic functional regulator FMR1 Human genes 0.000 description 4
- 201000007930 alcohol dependence Diseases 0.000 description 4
- 208000029560 autism spectrum disease Diseases 0.000 description 4
- 230000003925 brain function Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000009194 climbing Effects 0.000 description 4
- 235000019788 craving Nutrition 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 235000020937 fasting conditions Nutrition 0.000 description 4
- 239000007888 film coating Substances 0.000 description 4
- 238000009501 film coating Methods 0.000 description 4
- 210000001320 hippocampus Anatomy 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 230000007604 neuronal communication Effects 0.000 description 4
- 238000010855 neuropsychological testing Methods 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 208000000415 potassium-aggravated myotonia Diseases 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 230000011514 reflex Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000000284 resting effect Effects 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 210000003523 substantia nigra Anatomy 0.000 description 4
- 230000003936 working memory Effects 0.000 description 4
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- 208000011597 CGF1 Diseases 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 206010012335 Dependence Diseases 0.000 description 3
- 108010032606 Fragile X Mental Retardation Protein Proteins 0.000 description 3
- 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 3
- 206010029897 Obsessive thoughts Diseases 0.000 description 3
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 206010042008 Stereotypy Diseases 0.000 description 3
- 206010044688 Trisomy 21 Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 229940025084 amphetamine Drugs 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 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 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000001143 conditioned effect Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 210000001353 entorhinal cortex Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000005153 frontal cortex Anatomy 0.000 description 3
- 208000013403 hyperactivity Diseases 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000011813 knockout mouse model Methods 0.000 description 3
- 230000008449 language Effects 0.000 description 3
- 238000002595 magnetic resonance imaging Methods 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 230000004766 neurogenesis Effects 0.000 description 3
- 239000007935 oral tablet Substances 0.000 description 3
- 229940096978 oral tablet Drugs 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 230000003989 repetitive behavior Effects 0.000 description 3
- 208000013406 repetitive behavior Diseases 0.000 description 3
- 230000003252 repetitive effect Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000004039 social cognition Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000002889 sympathetic effect Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 2
- 206010001497 Agitation Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 206010012559 Developmental delay Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 101150082209 Fmr1 gene Proteins 0.000 description 2
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 description 2
- 101000652736 Homo sapiens Transgelin Proteins 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 235000014647 Lens culinaris subsp culinaris Nutrition 0.000 description 2
- 244000203494 Lens culinaris subsp culinaris Species 0.000 description 2
- 229920000161 Locust bean gum Polymers 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000029726 Neurodevelopmental disease Diseases 0.000 description 2
- 208000027089 Parkinsonian disease Diseases 0.000 description 2
- 206010034010 Parkinsonism Diseases 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 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
- 102100031013 Transgelin Human genes 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 102000003802 alpha-Synuclein Human genes 0.000 description 2
- 108090000185 alpha-Synuclein Proteins 0.000 description 2
- 230000003109 amnesic effect Effects 0.000 description 2
- 239000002269 analeptic agent Substances 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 201000007197 atypical autism Diseases 0.000 description 2
- 229940125717 barbiturate Drugs 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 230000006736 behavioral deficit Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000004638 bioanalytical method Methods 0.000 description 2
- 235000021152 breakfast Nutrition 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000003930 cognitive ability Effects 0.000 description 2
- 230000037411 cognitive enhancing Effects 0.000 description 2
- 230000003931 cognitive performance Effects 0.000 description 2
- 230000006854 communication Effects 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 238000013480 data collection Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000002598 diffusion tensor imaging Methods 0.000 description 2
- 230000009429 distress Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229920003130 hypromellose 2208 Polymers 0.000 description 2
- 229940031707 hypromellose 2208 Drugs 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000010365 information processing Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 235000010420 locust bean gum Nutrition 0.000 description 2
- 239000000711 locust bean gum Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 229940074869 marquis Drugs 0.000 description 2
- 230000006996 mental state Effects 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 229960001252 methamphetamine Drugs 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 239000004081 narcotic agent Substances 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 229940005483 opioid analgesics Drugs 0.000 description 2
- DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 2
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- VBUNOIXRZNJNAD-UHFFFAOYSA-N ponazuril Chemical compound CC1=CC(N2C(N(C)C(=O)NC2=O)=O)=CC=C1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 VBUNOIXRZNJNAD-UHFFFAOYSA-N 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- FTSUPYGMFAPCFZ-ZWNOBZJWSA-N quinpirole Chemical compound C([C@H]1CCCN([C@@H]1C1)CCC)C2=C1C=NN2 FTSUPYGMFAPCFZ-ZWNOBZJWSA-N 0.000 description 2
- 229950001037 quinpirole Drugs 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 230000000698 schizophrenic effect Effects 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000009182 swimming Effects 0.000 description 2
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 2
- 229950010357 tetrodotoxin Drugs 0.000 description 2
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 210000004515 ventral tegmental area Anatomy 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 230000031836 visual learning Effects 0.000 description 2
- 230000021542 voluntary musculoskeletal movement Effects 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- DGHFMPOTXCGXRM-HKGPVOKGSA-N (2s)-2-(2-oxopyrrolidin-1-yl)butanamide Chemical group CC[C@@H](C(N)=O)N1CCCC1=O.CC[C@@H](C(N)=O)N1CCCC1=O DGHFMPOTXCGXRM-HKGPVOKGSA-N 0.000 description 1
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical class N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- AOYNUTHNTBLRMT-SLPGGIOYSA-N 2-deoxy-2-fluoro-aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](F)C=O AOYNUTHNTBLRMT-SLPGGIOYSA-N 0.000 description 1
- FBTSQILOGYXGMD-LURJTMIESA-N 3-nitro-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C([N+]([O-])=O)=C1 FBTSQILOGYXGMD-LURJTMIESA-N 0.000 description 1
- LYUQWQRTDLVQGA-UHFFFAOYSA-N 3-phenylpropylamine Chemical compound NCCCC1=CC=CC=C1 LYUQWQRTDLVQGA-UHFFFAOYSA-N 0.000 description 1
- 208000017194 Affective disease Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 241000269627 Amphiuma means Species 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000036640 Asperger disease Diseases 0.000 description 1
- 201000006062 Asperger syndrome Diseases 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- KXCHXOCGUHFHNG-UHFFFAOYSA-N C1OC(C=2OCC=2)=C1 Chemical compound C1OC(C=2OCC=2)=C1 KXCHXOCGUHFHNG-UHFFFAOYSA-N 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010510 Congenital hypothyroidism 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
- 206010011971 Decreased interest Diseases 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 208000035976 Developmental Disabilities Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000021663 Female sexual arousal disease Diseases 0.000 description 1
- 206010016845 Foetal alcohol syndrome Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101150014889 Gad1 gene Proteins 0.000 description 1
- 102100035902 Glutamate decarboxylase 1 Human genes 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920000569 Gum karaya Polymers 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 101000828537 Homo sapiens Synaptic functional regulator FMR1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 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 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000036769 Mild mental retardation Diseases 0.000 description 1
- 208000036831 Moderate mental retardation Diseases 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 208000033180 Monosomy 22q13.3 Diseases 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 208000003090 Mowat-Wilson syndrome Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 208000035023 Oculocerebrorenal syndrome of Lowe Diseases 0.000 description 1
- 206010033664 Panic attack Diseases 0.000 description 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
- 201000006880 Phelan-McDermid syndrome Diseases 0.000 description 1
- 201000011252 Phenylketonuria Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 1
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 208000036623 Severe mental retardation Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000934878 Sterculia Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 206010049644 Williams syndrome Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 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
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003935 attention Effects 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 238000013542 behavioral therapy Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000002599 biostatic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000007698 birth defect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229940078456 calcium stearate Drugs 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 208000031214 ciliopathy Diseases 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 230000006998 cognitive state Effects 0.000 description 1
- 238000009226 cognitive therapy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125368 controlled substance Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 229960000632 dexamfetamine Drugs 0.000 description 1
- -1 dextrates Polymers 0.000 description 1
- 229940096516 dextrates Drugs 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 210000004002 dopaminergic cell Anatomy 0.000 description 1
- 235000012489 doughnuts Nutrition 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 230000006397 emotional response Effects 0.000 description 1
- 229960004341 escitalopram Drugs 0.000 description 1
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 208000026934 fetal alcohol spectrum disease Diseases 0.000 description 1
- 201000007794 fetal alcohol syndrome Diseases 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 description 1
- 229940046813 glyceryl palmitostearate Drugs 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 210000004326 gyrus cinguli Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 230000008801 hippocampal function Effects 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 1
- 238000012880 independent component analysis Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 210000001153 interneuron Anatomy 0.000 description 1
- 235000010494 karaya gum Nutrition 0.000 description 1
- 239000000231 karaya gum Substances 0.000 description 1
- 229940039371 karaya gum Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 238000011670 long-evans rat Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 229920000940 maneb Polymers 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 230000010387 memory retrieval Effects 0.000 description 1
- 230000036630 mental development Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229940042472 mineral oil Drugs 0.000 description 1
- 239000008185 minitablet Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 230000001473 noxious effect Effects 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
- 201000006352 oculocerebrorenal syndrome Diseases 0.000 description 1
- 229940100691 oral capsule Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 210000001769 parahippocampal gyrus Anatomy 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000008529 pathological progression Effects 0.000 description 1
- 230000009984 peri-natal effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229940023488 pill Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 210000002442 prefrontal cortex Anatomy 0.000 description 1
- 230000002360 prefrontal effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 229940080817 rotenone Drugs 0.000 description 1
- JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 230000003997 social interaction Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940125794 sodium channel blocker Drugs 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000009154 spontaneous behavior Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000024188 startle response Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 230000009184 walking Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- 229940057977 zinc stearate Drugs 0.000 description 1
Images
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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61P25/08—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
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562165812P | 2015-05-22 | 2015-05-22 | |
| US62/165,812 | 2015-05-22 | ||
| CN201680037483.XA CN107810002B (zh) | 2015-05-22 | 2016-05-20 | 左乙拉西坦的延时释放药物组合物 |
| US15/160,424 US10159648B2 (en) | 2015-05-22 | 2016-05-20 | Extended release pharmaceutical compositions of levetiracetam |
| PCT/US2016/033567 WO2016191288A1 (en) | 2015-05-22 | 2016-05-20 | Extended release pharmaceutical compositions of levetiracetam |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201680037483.XA Division CN107810002B (zh) | 2015-05-22 | 2016-05-20 | 左乙拉西坦的延时释放药物组合物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112843005A CN112843005A (zh) | 2021-05-28 |
| CN112843005B true CN112843005B (zh) | 2023-02-21 |
Family
ID=56117989
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011470929.2A Active CN112843005B (zh) | 2015-05-22 | 2016-05-20 | 左乙拉西坦的延时释放药物组合物 |
| CN201680037483.XA Active CN107810002B (zh) | 2015-05-22 | 2016-05-20 | 左乙拉西坦的延时释放药物组合物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201680037483.XA Active CN107810002B (zh) | 2015-05-22 | 2016-05-20 | 左乙拉西坦的延时释放药物组合物 |
Country Status (13)
| Country | Link |
|---|---|
| US (4) | US10159648B2 (enExample) |
| JP (4) | JP6899043B2 (enExample) |
| CN (2) | CN112843005B (enExample) |
| AU (3) | AU2016268096B2 (enExample) |
| BR (1) | BR112017025031B1 (enExample) |
| CA (1) | CA2986598C (enExample) |
| EA (1) | EA034167B8 (enExample) |
| HK (1) | HK1251980B (enExample) |
| IL (3) | IL255782B (enExample) |
| MX (2) | MX384391B (enExample) |
| NZ (1) | NZ738682A (enExample) |
| WO (1) | WO2016191288A1 (enExample) |
| ZA (2) | ZA201708703B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2346500B1 (en) * | 2008-10-16 | 2017-05-17 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| CA2904767C (en) | 2013-03-15 | 2022-06-21 | Agenebio, Inc. | Methods and compositions for improving cognitive function |
| US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| EA034167B8 (ru) | 2015-05-22 | 2021-04-27 | Эйджинбайо, Инк. | Фармацевтические композиции леветирацетама пролонгированного высвобождения |
| US20180170941A1 (en) | 2016-12-19 | 2018-06-21 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| US20220193028A1 (en) * | 2019-04-18 | 2022-06-23 | Prevep Llc | Therapeutic combinations, liquid pharmaceutical compositions, kits for their preparation, and methods of their use |
| US20240423953A1 (en) * | 2021-01-26 | 2024-12-26 | The Regents Of The University Of California | Methods and compositions for targeting sv2 proteins for immune regulation |
| IL316051A (en) * | 2022-04-01 | 2024-11-01 | Agenebio Inc | Methods for preventing or slowing the progression of cognitive decline or impairment in subjects displaying normal cognitive performance |
| EP4572852A1 (en) | 2022-08-19 | 2025-06-25 | Agenebio, Inc. | Benzazepine derivatives, compositions, and methods for treating cognitive impairment |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008006528A2 (en) * | 2006-07-13 | 2008-01-17 | Ucb Pharma, S.A. | Pharmaceutical compositions comprising levetiracetam |
| WO2008062446A2 (en) * | 2006-09-14 | 2008-05-29 | Alembic Limited | An extended release composition of levetiracetam, which exhibits no adverse food effect |
| WO2012070785A1 (en) * | 2010-11-23 | 2012-05-31 | Bio Pharmartis Co., Ltd. | Sustained-release pharmaceutical composition comprising levetiracetam or pharmaceutically acceptable salt thereof having improved dissolution stability and method for manufacturing the same |
| WO2012159609A1 (de) * | 2011-05-26 | 2012-11-29 | Stada Arzneimittel Ag | Pulverförmige mischung zur herstellung von levetiracetam-haltigen tabletten |
Family Cites Families (234)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT535124A (enExample) | 1952-09-20 | |||
| JP2000319257A (ja) | 1969-01-06 | 2000-11-21 | Eisai Co Ltd | １−ベンジル−４−［（５，６−ジメトキシ−２−フルオロ−１−インダノン）−２−イル］メチルピペリジン |
| IT1045043B (it) | 1975-08-13 | 1980-04-21 | Isf Spa | Derivati pirrolidinici |
| IT1075280B (it) | 1977-02-11 | 1985-04-22 | Isf Spa | Procedimento per la preparazione di derivati pirrolidinici |
| BE864269A (fr) | 1977-03-03 | 1978-06-16 | Parke Davis & Co | Nouveaux n-(aminoalkyl substitue)-2-oxo-1-pyrrolidine-acetamides et procedes pour les produire |
| ATE27T1 (de) | 1978-05-08 | 1981-04-15 | Ucb Sa | Lactam-n-essigsaeuren und ihre amide, verfahren zu ihrer herstellung und heilmittel, die sie enthalten |
| US4654370A (en) | 1979-03-12 | 1987-03-31 | Abbott Laboratories | Glyceryl valproates |
| US4372960A (en) | 1980-12-12 | 1983-02-08 | Warner-Lambert Company | Quaternary derivatives of N-(substituted-aminoalkyl)-2-oxo-1-pyrrolidine-acetamides as cognition activators |
| FR2515179A1 (fr) | 1981-07-24 | 1983-04-29 | Hoffmann La Roche | Derives de pyrrolidine, leur procede de preparation, les intermediaires pour leur synthese et leur application therapeutique |
| IL67623A (en) | 1983-01-05 | 1984-09-30 | Teva Pharma | 1'-ethoxycarbonyloxyethyl ester of valproic acid,its preparation and pharmaceutical compositions containing it |
| IL72381A (en) | 1983-07-20 | 1988-03-31 | Sanofi Sa | Pharmaceutical composition based on valproic acid |
| US4558070A (en) | 1983-10-26 | 1985-12-10 | Abbott Laboratories | Acid salts of valproic acid |
| GB8412358D0 (en) | 1984-05-15 | 1984-06-20 | Ucb Sa | Pharmaceutical composition |
| GB8412357D0 (en) | 1984-05-15 | 1984-06-20 | Ucb Sa | Pharmaceutical composition |
| US4668687A (en) | 1984-07-23 | 1987-05-26 | Bristol-Myers Company | Psychogeriatric 1-(2-pyrimidinyl)piperazinyl derivatives of 1-pyrrolidin-2-ones |
| US4913906B1 (en) | 1985-02-28 | 2000-06-06 | Yissum Res Dev Co | Controlled release dosage form of valproic acid |
| IL74497A (en) | 1985-03-05 | 1990-02-09 | Proterra Ag | Pharmaceutical compositions containing phenyl carbamate derivatives and certain phenyl carbamate derivatives |
| JPS6222785A (ja) | 1985-07-23 | 1987-01-30 | Sanwa Kagaku Kenkyusho:Kk | 新規な２−オキソピロリジン化合物及びその塩、その製法並びにこれらを有効成分とする脳機能障害の予防及び治療剤 |
| US4663318A (en) | 1986-01-15 | 1987-05-05 | Bonnie Davis | Method of treating Alzheimer's disease |
| IT1190133B (it) | 1986-06-19 | 1988-02-10 | Chiesi Farma Spa | Derivati di acido valproico e di acido (e)-2-valproenoico,procedimento per la loro preparazione e relative composizioni farmaceutiche |
| US4816456A (en) | 1986-10-01 | 1989-03-28 | Summers William K | Administration of monoamine acridines in cholinergic neuronal deficit states |
| NL195004C (nl) | 1987-03-04 | 2003-11-04 | Novartis Ag | Fenylcarbamaat bevattend farmaceutisch preparaat. |
| PH25124A (en) | 1987-03-17 | 1991-02-19 | Hoechst Roussel Pharma | Substituted 9-amino-tetrahydro acridines and related compounds |
| DE3709230A1 (de) | 1987-03-20 | 1988-10-06 | Desitin Arzneimittel Gmbh | Neues calciumsalz der valproinsaeure |
| IT1225462B (it) | 1987-04-03 | 1990-11-14 | Mediolanum Farmaceutici Srl | Sali organici di derivati della fisostigmina |
| US5002955A (en) | 1987-04-23 | 1991-03-26 | Hoechst-Roussel Pharmaceuticals Inc. | Fused heteroalkylene quinolinamines and use as cholinergic agents |
| DE3856594D1 (de) | 1987-05-04 | 2008-11-27 | Bonnie Davis | Mittel zur behandlung der alzheimer-krankheit |
| US5187165A (en) | 1987-05-15 | 1993-02-16 | Hoechst-Roussel Pharmaceuticals Inc. | Memory enhancing and analgesic 1,2,3a,8,8a-hexahydro-3a,8(and 1,3a,8)-di(and tri)methylpyrrolo[2,3-b]indoles |
| FI95572C (fi) | 1987-06-22 | 1996-02-26 | Eisai Co Ltd | Menetelmä lääkeaineena käyttökelpoisen piperidiinijohdannaisten tai sen farmaseuttisen suolan valmistamiseksi |
| JPS6422883A (en) | 1987-07-17 | 1989-01-25 | Sanwa Kagaku Kenkyusho Co | 1-pyrrolidine acetamide derivative, its salt, production thereof and prophylactic and remedial agent for cereral dysfunction containing said derivative and salt as active ingredient |
| DE3773926D1 (de) | 1987-07-22 | 1991-11-21 | Farvalsa Ag | Feuchtigkeitsstabile feste valproinsaeure-zubereitung und verfahren zu ihrer herstellung. |
| US4950658A (en) | 1988-12-06 | 1990-08-21 | Board Of Trustees Of Southern Illinois Univ. | Method of medical treatment of Alzheimer's disease |
| HUT53607A (en) | 1989-01-17 | 1990-11-28 | Hoffmann La Roche | Process for production of derivatives of cyclohexan-acetamid |
| FR2643556B1 (fr) | 1989-02-27 | 1993-03-05 | Sanofi Sa | Composition pharmaceutique a liberation prolongee d'acide valproique |
| US4981870A (en) | 1989-03-07 | 1991-01-01 | Pfizer Inc. | Use of 4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine derivatives in the treatment of psychosis, inflammation and as immunosuppressants |
| US5238945A (en) | 1989-04-11 | 1993-08-24 | H. Lundbeck A/S | Method of treating psychoses |
| US5364866A (en) | 1989-05-19 | 1994-11-15 | Hoechst-Roussel Pharmaceuticals, Inc. | Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics |
| US5693668A (en) | 1989-06-22 | 1997-12-02 | Merrell Pharmaceuticals Inc. | Acetylcholinesterase inhibitors |
| EP0403713A1 (en) | 1989-06-22 | 1990-12-27 | Merrell Dow Pharmaceuticals Inc. | Novel acetylcholinesterase inhibitors |
| IT1231477B (it) | 1989-07-12 | 1991-12-07 | Sigma Tau Ind Farmaceuti | (pirrolidin-2-one-1-il) acetammidi quali attivatori dei processi di apprendimento e della memoria e composizioni farmaceutiche comprendenti tali composti |
| US4999430A (en) | 1989-07-31 | 1991-03-12 | Warner-Lambert Company | Derivatives of 1,2,3,4-tetrahydro-9-acrisinamine |
| DE3927049A1 (de) | 1989-08-16 | 1991-02-21 | Sandoz Ag | Halogenalkyl-phenyl-ketone und deren hydrate, ihre herstellung und verwendung |
| US5387590A (en) | 1989-08-30 | 1995-02-07 | Pfizer Inc. | Benzazabicyclic carbamates as novel cholinesterase inhibitors |
| US4914102A (en) | 1989-09-28 | 1990-04-03 | Hoechst Roussel Pharmaceuticals, Inc. | N-aminocarbamates related to physostigmine, pharmacentical compositions and use |
| NZ237241A (en) | 1990-03-02 | 1993-11-25 | Pharmetrix Corp | Method for increasing the storage stability of physostigmine |
| JP2807577B2 (ja) | 1990-06-15 | 1998-10-08 | エーザイ株式会社 | 環状アミド誘導体 |
| US5102891A (en) | 1990-07-23 | 1992-04-07 | Hoechst-Roussel Pharmaceuticals Inc. | 1-(substituted pyridinylamino)-1H-indol-5-yl substituted carbamates |
| US5264442A (en) | 1990-08-13 | 1993-11-23 | Hoechst-Roussel Pharmaceuticals Incorporated | Carbamoyl-1-(pyridinylalkyl)-1H-indoles, indolines and related analogs |
| TW200462B (enExample) | 1990-09-27 | 1993-02-21 | Hoechst Roussel Pharma | |
| US5190951A (en) | 1990-10-19 | 1993-03-02 | Ss Pharmaceutical Co., Ltd. | Quinoline derivatives |
| JP2965675B2 (ja) | 1990-11-21 | 1999-10-18 | エーザイ株式会社 | （―）―１―ベンジル―４―〔（５，６―ジメトキシ―１―インダノン）―２―イル〕メチルピペリジンの製造方法 |
| TW197435B (enExample) | 1990-11-22 | 1993-01-01 | Takeda Pharm Industry Co Ltd | |
| US5668117A (en) | 1991-02-22 | 1997-09-16 | Shapiro; Howard K. | Methods of treating neurological diseases and etiologically related symptomology using carbonyl trapping agents in combination with previously known medicaments |
| PL171914B1 (pl) | 1991-03-28 | 1997-06-30 | Eisai Co Ltd | Sposób wytwarzania pochodnych aminy heterocyklicznej PL PL PL PL PL PL PL |
| US5750542A (en) | 1993-09-28 | 1998-05-12 | Pfizer | Benzisoxazole and benzisothizole derivatives as cholinesterase inhibitors |
| US5104880A (en) | 1991-05-01 | 1992-04-14 | Mayo Foundation For Medical Education And Research | Huperzine a analogs as acetylcholinesterase inhibitors |
| SK279285B6 (sk) | 1991-05-02 | 1998-09-09 | Daiichi Pharmaceutical Co. | Použitie n-(2,6-dimetylfenyl)-2-(2-oxo-1-pyrolidin |
| FR2677019B1 (fr) | 1991-05-27 | 1994-11-25 | Pf Medicament | Nouvelles piperidines disubstituees-1,4, leur preparation et leur application en therapeutique. |
| US5106856A (en) | 1991-06-07 | 1992-04-21 | Hoechst-Roussel Pharmaceuticals Inc. | [(Arylalkylpiperidin-4-yl)methyl]-2a,3,4,5-tetrahydro-1(2H)-acenaphthylen-1-ones and related compounds |
| FR2679555B1 (fr) | 1991-07-25 | 1993-11-19 | Fabre Medicament Pierre | Nouveaux derives de l'uree, leur preparation et leur application en therapeutique. |
| EP0597956A1 (en) | 1991-07-29 | 1994-05-25 | Warner-Lambert Company | Quinazoline derivatives as acetylcholinesterase inhibitors |
| IT1251166B (it) | 1991-08-09 | 1995-05-04 | Chiesi Farma Spa | Derivati di geneserina,loro preparazione e composizioni farmaceutiche che li contengono |
| US5246947A (en) | 1991-09-23 | 1993-09-21 | Hoechst-Roussel Pharmaceuticals Incorporated | Substituted pyridinylamino-1,2-benzisothiazoles and their use for treating depression |
| US5231093A (en) | 1991-10-01 | 1993-07-27 | Hoechst-Roussel Pharmaceuticals Incorporated | Carbamate derivatives of 4-amino-3-isoxazolidinones, 3-amino-1-hydroxypyrrolidin-2-ones and 1-amino-1-cyclopropanecarboxylic acid analogs |
| TW263504B (enExample) | 1991-10-03 | 1995-11-21 | Pfizer | |
| ES2042384B1 (es) | 1991-12-26 | 1994-06-01 | Boehringer Ingelheim Espana | Procedimiento para obtener derivados bis-piridinicos. |
| CA2126976A1 (en) | 1991-12-31 | 1993-07-08 | Hisashi Takasugi | Oxadiazole derivatives having acetylcholinesterase-inhibitory and muscarinic agonist activity |
| CA2129732A1 (en) | 1992-02-25 | 1993-09-02 | Alain Martin | Cytoprotective compositions containing pyruvate and antioxidants |
| US5439930A (en) | 1992-04-14 | 1995-08-08 | Russian-American Institute For New Drug Development | Biologically active n-acylprolydipeptides having antiamnestic, antihypoxic and anorexigenic effects |
| IT1254996B (it) | 1992-06-25 | 1995-10-11 | Mediolanum Farmaceutici Srl | Esteri amminoalchilcarbammici dell'eserolina atti all'impiego come anticolinesterasici e relativo procedimento di preparazione |
| US5440023A (en) | 1992-09-18 | 1995-08-08 | Beckman Instruments, Inc. | Method for making valproic acid derivatives |
| TW251284B (enExample) | 1992-11-02 | 1995-07-11 | Pfizer | |
| EP0611769A1 (en) | 1993-02-16 | 1994-08-24 | Merrell Dow Pharmaceuticals Inc. | Silylated acetylcholinesterase inhibitors |
| WO1994020476A1 (fr) | 1993-03-02 | 1994-09-15 | Fujisawa Pharmaceutical Co., Ltd. | Nouveau compose heterocyclique |
| EP0627400A1 (en) | 1993-06-04 | 1994-12-07 | Merrell Dow Pharmaceuticals Inc. | Aromatic acetylcholinesterase inhibitors |
| SE9302080D0 (sv) | 1993-06-16 | 1993-06-16 | Ab Astra | New compounds |
| GB9319732D0 (en) | 1993-09-24 | 1993-11-10 | Ucb Sa | Use of (s)-alpha-ethyl-2-oxo-l-pyrrolidineacetamide for the treatment of anxiety |
| US5744476A (en) | 1994-06-27 | 1998-04-28 | Interneuron Pharmaceuticals, Inc. | Dopamine D1 agonists for the treatment of dementia |
| IL118279A (en) | 1995-06-07 | 2006-10-05 | Abbott Lab | Compounds 3 - Pyridyloxy (or Thio) Alkyl Heterocyclic Pharmaceutical Compositions Containing Them and Their Uses for Preparing Drugs to Control Synaptic Chemical Transmission |
| IL115113A (en) | 1995-08-31 | 2002-11-10 | Israel State | 3-carbamoyloxy pyridinium derivatives and pharmaceutical compositions containing them |
| ES2100129B1 (es) | 1995-10-11 | 1998-02-16 | Medichem Sa | Nuevos compuestos aminopiridinicos policiclicos inhibidores de acetilcolinesterasa, procedimiento para su preparacion y su utilizacion. |
| ATE240942T1 (de) | 1995-11-17 | 2003-06-15 | Merck & Co Inc | Neue substituierte aryl-verbindungen als acetylcholine receptors modulatoren |
| US5783584A (en) | 1995-12-11 | 1998-07-21 | Mayo Foundation For Medical Education And Research | THA analogs useful as cholinesterase inhibitors |
| GB9606736D0 (en) | 1996-02-19 | 1996-06-05 | Shire International Licensing | Therapeutic method |
| WO1997038993A1 (en) | 1996-04-12 | 1997-10-23 | Hoechst Marion Roussel, Inc. | Isatin derivatives as acetylcholinesterase inhibitors and analgesics |
| WO1997046526A1 (en) | 1996-06-07 | 1997-12-11 | Eisai Co., Ltd. | Stable polymorphs of donepezil (1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine) hydrochloride and process for production |
| TW513409B (en) | 1996-06-07 | 2002-12-11 | Eisai Co Ltd | Polymorphs of donepezil hydrochloride |
| CA2180703A1 (en) | 1996-07-08 | 1998-01-09 | Paul Marie Victor Gilis | Fast-dissolving galanthamine hydrobromide tablet |
| AU747708B2 (en) | 1996-07-24 | 2002-05-23 | Du Pont Pharmaceuticals Company | Azolo triazines and pyrimidines |
| WO1998007431A1 (en) | 1996-08-22 | 1998-02-26 | New York University | Cholinesterase inhibitors for treatment of parkinson's disease |
| IT1285801B1 (it) | 1996-10-10 | 1998-06-24 | Sigma Tau Ind Farmaceuti | Procedimento migliorato per la preparazione dell'acido valproico |
| WO1998030243A1 (en) | 1997-01-08 | 1998-07-16 | Warner-Lambert Company | Acetylcholinesterase inhibitors in combination with muscarinic agonists for the treatment of alzheimer's disease |
| DE69815090T2 (de) | 1997-03-03 | 2004-02-19 | Eisai Co., Ltd. | Verwendung von cholinesterasehemmer zur behandlung von konzentrationsstörungen |
| GB9716879D0 (en) | 1997-08-08 | 1997-10-15 | Shire Int Licensing Bv | Treatment of attention deficit disorders |
| WO1999008672A1 (en) | 1997-08-15 | 1999-02-25 | Shire International Licensing Bv | Use of cholinesterase inhibitor for treating diseases associated with proteolytic enzyme activity |
| US6479523B1 (en) | 1997-08-26 | 2002-11-12 | Emory University | Pharmacologic drug combination in vagal-induced asystole |
| UA72189C2 (uk) | 1997-11-17 | 2005-02-15 | Янссен Фармацевтика Н.В. | Фармацевтична композиція, що містить водну суспензію субмікронних ефірів 9-гідроксирисперидон жирних кислот |
| WO1999029668A1 (en) | 1997-12-05 | 1999-06-17 | Eisai Co., Ltd. | Donepezil polycrystals and process for producing the same |
| US6131106A (en) | 1998-01-30 | 2000-10-10 | Sun Microsystems Inc | System and method for floating-point computation for numbers in delimited floating point representation |
| GB9805561D0 (en) | 1998-03-16 | 1998-05-13 | Merck Sharp & Dohme | A combination of therapeutic agents |
| US6262081B1 (en) | 1998-07-10 | 2001-07-17 | Dupont Pharmaceuticals Company | Composition for and method of treating neurological disorders |
| US6218383B1 (en) | 1998-08-07 | 2001-04-17 | Targacept, Inc. | Pharmaceutical compositions for the prevention and treatment of central nervous system disorders |
| IL125809A (en) | 1998-08-17 | 2005-08-31 | Finetech Lab Ltd | Process and intermediates for production of donepezil and related compounds |
| IT1304904B1 (it) | 1998-09-11 | 2001-04-05 | Eisai Co Ltd | Derivati anticolinesterasici per il trattamento delle sindromidolorose funzionali e/o organiche |
| AU6472799A (en) | 1998-10-16 | 2000-05-08 | Janssen Pharmaceutica N.V. | Therapy for improving cognition |
| WO2000030446A1 (en) | 1998-11-23 | 2000-06-02 | Bonnie Davis | Dosage formulations for acetylcholinesterase inhibitors |
| CA2354035A1 (en) | 1998-12-11 | 2000-06-15 | Bonnie Davis | Use of acetylcholinesterase inhibitors on the modulation of the hypothalamic-pituitary-gonadal axis |
| US6277866B1 (en) | 1999-03-03 | 2001-08-21 | Eisai Co., Ltd. | 1-benzyl-4[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methylpiperidine |
| US6372760B1 (en) | 1999-03-31 | 2002-04-16 | Eisai Co., Ltd. | Stabilized composition comprising antidementia medicament |
| EP1050303A3 (en) | 1999-04-27 | 2003-01-15 | Pfizer Products Inc. | Methods and compositions for treating age-related behavioral disorders in companion animals |
| US6524616B1 (en) | 1999-06-25 | 2003-02-25 | Wake Forest University Health Services | Compositions and methods for treating or preventing neurodegeneration and cognitive decline and dysfunction associated with alzheimer's disease, aging, other dementia related disorders and estrogen deficiency related conditions |
| ES2284519T3 (es) | 1999-09-01 | 2007-11-16 | EISAI R&D MANAGEMENT CO., LTD. | Derivados de piperidina 4-sustituida. |
| JP4242048B2 (ja) | 1999-09-01 | 2009-03-18 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ４−置換ピペリジン誘導体 |
| HK1043590A1 (zh) | 1999-09-22 | 2002-09-20 | Schering Corporation | 毒蕈碱性拮抗物 |
| US6620802B1 (en) | 1999-11-23 | 2003-09-16 | Corcept Therapeutics, Inc. | Methods of treating mild cognitive impairment using a glucocorticoid-specific receptor antagonist |
| CA2392879C (en) | 1999-12-01 | 2005-03-29 | Ucb, S.A. | A pyrrolidineacetamide derivative alone or in combination for treatment of cns disorders |
| DE60124730T2 (de) | 2000-03-03 | 2007-10-04 | Eisai R&D Management Co., Ltd. | Neue methoden unter verwendung von cholinesteraseinhibitoren |
| AU2001239052A1 (en) | 2000-03-06 | 2001-09-17 | Immune Network Ltd. | Compositions for prevention and treatment of dementia |
| EP1285656A4 (en) | 2000-04-13 | 2006-07-12 | Eisai Co Ltd | ACETYLCHOLINESTERASE HEMMER CONTAINING 1-BENZYLPYRIDINIUM SALT |
| US20010036949A1 (en) | 2000-05-09 | 2001-11-01 | Coe Jotham Wadsworth | Pharmaceutical composition and method of treatment of diseases of cognitive dysfunction in a mammal |
| US6756385B2 (en) | 2000-07-31 | 2004-06-29 | Pfizer Inc. | Imidazole derivatives |
| US20020151591A1 (en) | 2000-10-17 | 2002-10-17 | Anabella Villalobos | Combination use of acetylcholinesterase inhibitors and GABAa inverse agonists for the treatment of cognitive disorders |
| KR100823668B1 (ko) | 2000-12-28 | 2008-04-21 | 해밀턴 파마슈티컬스 인코포레이티드 | 신경성 통증 치료 및 예방약 |
| US6610326B2 (en) | 2001-02-16 | 2003-08-26 | Andrx Corporation | Divalproex sodium tablets |
| WO2002067931A1 (en) | 2001-02-23 | 2002-09-06 | Johns Hopkins University | Treatment of tics, tremors and related disorders |
| JP2004532200A (ja) | 2001-03-15 | 2004-10-21 | サエジス ファーマシューティカルズ， インコーポレイテッド | 全身性ストレスの後に認識機能を回復するための方法 |
| DE60208630T2 (de) | 2001-05-11 | 2006-08-17 | Pfizer Products Inc., Groton | Thiazolderivate und ihre Verwendung als cdk-Inhibitoren |
| US8354438B2 (en) | 2001-08-08 | 2013-01-15 | Michael Chez | Neurological functions |
| ATE404192T1 (de) | 2001-08-22 | 2008-08-15 | Hamilton Pharmaceuticals Inc | Verwendung von nefiracetam zur behandlung von postischemischer neurodegeneration |
| CA2459146A1 (en) | 2001-08-30 | 2003-03-13 | Ortho-Mcneil Pharmaceutical, Inc. | Treatment of dementia and memory disorders with anticonvulsants and acetylcholinesterase inhibitors |
| WO2003032981A1 (en) | 2001-10-16 | 2003-04-24 | Memory Pharmaceuticals Corporation | 4-(4-alkoxy-3-hydroxyphenyl)-2-pyrrolidone derivatives as pde-4 inhibitors for the treatment of neurological syndromes |
| US6495700B1 (en) | 2002-01-09 | 2002-12-17 | Axonyx, Inc. | Process for producing phenserine and its analog |
| US6759552B2 (en) | 2002-03-28 | 2004-07-06 | Council Of Scientific And Industrial Research | Compound as cholinesterase inhibitor and its isolation from fungus sporotrichum species |
| ES2297141T3 (es) | 2002-03-29 | 2008-05-01 | EISAI R&D MANAGEMENT CO., LTD. | Derivados de (1-indanona)-(1,2,3,6-tetrahidropiridina). |
| DE60324544D1 (de) | 2002-04-26 | 2008-12-18 | Schering Corp | Muskarin antagonisten |
| WO2004034963A2 (en) | 2002-05-17 | 2004-04-29 | Eisai Co., Ltd. | Methods and compositions using cholinesterase inhibitors |
| EP1509232B1 (en) | 2002-05-31 | 2008-11-19 | H. Lundbeck A/S | A combination of an nmda-antagonist and acetylcholine esterase inhibitors for the treatment of alzheimer's disease |
| US20040116506A1 (en) | 2002-06-20 | 2004-06-17 | Krusz John Claude | Use of levetiracetam for treating or preventing acute headaches |
| US7557137B2 (en) | 2002-08-05 | 2009-07-07 | Bristol-Myers Squibb Company | Gamma-lactams as beta-secretase inhibitors |
| US7635709B2 (en) | 2002-09-26 | 2009-12-22 | The United States Of America As Represented By The Department Of Veterans Affairs | Compositions and methods for bowel care in individuals with chronic intestinal pseudo-obstruction |
| GB0223494D0 (en) | 2002-10-09 | 2002-11-13 | Neuropharma Sa | Dual binding site acetylcholinesterase inhibitors for the treatment of alzheimer's disease |
| CN100339070C (zh) | 2002-10-24 | 2007-09-26 | 莫茨药物股份两合公司 | 包含1－氨基环己烷衍生物类和乙酰胆碱酯酶抑制剂类的药物组合物 |
| MXPA05005398A (es) | 2002-11-22 | 2006-03-09 | Univ Johns Hopkins | Meta para terapia de deterioro cognitivo. |
| US7090985B2 (en) | 2002-12-03 | 2006-08-15 | Ucb, S.A. | Methods for the identification of agents for the treatment of seizures, neurological diseases, endocrinopathies and hormonal diseases |
| WO2004051222A2 (en) | 2002-12-03 | 2004-06-17 | Ucb, S.A. | Methods for the identification of agents for the treatment of seizures, neurological diseases, endocrinopathies and hormonal diseases |
| AU2003279492A1 (en) | 2002-12-11 | 2004-06-30 | Pharmacia & Upjohn Company Llc | Treatment of diseases with combinations of alpha 7 nicotinic acetylcholine receptor agonists and other compounds |
| ZA200507322B (en) | 2003-03-06 | 2007-03-28 | Celgene Corp | Selective cytokine inhibitory drugs for treating disorders of the central nervous system |
| US20040191334A1 (en) | 2003-03-24 | 2004-09-30 | Pang-Chui Shaw | Use of transhinone derivates as cholinesterase inhibitors in treating related diseases |
| ITMI20030573A1 (it) | 2003-03-24 | 2004-09-25 | Nikem Research Srl | Composti ad azione nootropica, loro preparazione, |
| US7732162B2 (en) | 2003-05-05 | 2010-06-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases |
| ZA200508306B (en) | 2003-05-23 | 2007-03-28 | Otsuka Pharma Co Ltd | Carbostyril derivatives and mood stabilizers for treating mood disorders |
| GB0322140D0 (en) | 2003-09-22 | 2003-10-22 | Pfizer Ltd | Combinations |
| US7244843B2 (en) | 2003-10-07 | 2007-07-17 | Bristol-Myers Squibb Company | Modulators of serotonin receptors |
| MXPA06003748A (es) | 2003-10-08 | 2006-06-14 | Pfizer | Compuestos de lactama condensada. |
| WO2005039580A1 (en) | 2003-10-16 | 2005-05-06 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition comprising a monoamine neurotransmitter re-uptake inhibitor and an acetylcholinesterase inhibitor |
| US7897639B2 (en) | 2003-10-21 | 2011-03-01 | Colucid Pharmaceuticals, Inc. | Carbamoyl esters that inhibit cholinesterase and release pharmacologically active agents |
| US20050222123A1 (en) | 2004-01-27 | 2005-10-06 | North Shore-Long Island Jewish Research Institute | Cholinesterase inhibitors for treating inflammation |
| WO2005074535A2 (en) | 2004-01-30 | 2005-08-18 | Eisai Co., Ltd. | Cholinesterase inhibitors for spinal cord disorders |
| EP1727538A2 (en) | 2004-02-13 | 2006-12-06 | Neuromolecular Inc. | Combination of an nmda receptor antagonist and an anti-epileptic drug for the treatment of epilepsy and other cns disorders |
| US20050182044A1 (en) | 2004-02-17 | 2005-08-18 | Bruinsma Gosse B. | Combinatorial therapy with an acetylcholinesterase inhibitor and (3aR)-1,3a,8-trimethyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3,-b]indol-5-yl phenylcarbamate |
| CA2556390C (en) | 2004-02-25 | 2012-10-02 | Eli Lilly And Company | 6-substituted 2,3,4,5-tetrahydro-1h-benzo[d]azepines as 5-ht2c receptor agonists |
| JP2007529556A (ja) | 2004-03-19 | 2007-10-25 | アクソニクス インコーポレイテッド | 認知障害の処置に有用なアセチルコリンエステラーゼ阻害剤およびｎ−メチル−ｄ−アスパラギン酸拮抗剤 |
| US7618978B2 (en) | 2004-04-22 | 2009-11-17 | Eli Lilly And Company | Amides as BACE inhibitors |
| US20070212428A1 (en) | 2004-06-04 | 2007-09-13 | Mood Management Sciences, Inc. | Methods and compositions for treating mood disorder |
| EP1758600A4 (en) | 2004-06-04 | 2008-03-05 | Mood Man Sciences Llc | METHOD AND COMPOSITIONS FOR TREATING MUTUAL DISORDER |
| CN1964942A (zh) | 2004-06-11 | 2007-05-16 | Ucb股份有限公司 | 通过分子内烯丙基化制备2－氧代－1－吡咯烷衍生物的方法 |
| US20060063707A1 (en) | 2004-09-17 | 2006-03-23 | Lifelike Biomatic, Inc. | Compositions for enhancing memory and methods therefor |
| EP1807087A2 (en) | 2004-10-12 | 2007-07-18 | Ernir Snorrason | Inhibitors of acetylcholinesterase for treating skin diseases |
| ATE504582T1 (de) | 2004-10-18 | 2011-04-15 | Lilly Co Eli | Substituierte benzopyrane als selektive östrogenrezeptor-beta-agonisten |
| WO2006060082A1 (en) | 2004-10-22 | 2006-06-08 | THE GOVERNMENT OF THE U.S.A. as represented by THE SEC., DEPT. OF HEALTH & HUMAN SERVICES, NATIONAL INSTITUTES OF HEALTH | Tricyclic compounds, preparation thereof and use thereof as cholinesterase activity inhibitors |
| US8058291B2 (en) | 2005-04-06 | 2011-11-15 | Adamas Pharmaceuticals, Inc. | Methods and compositions for the treatment of CNS-related conditions |
| EP2425846A1 (en) | 2004-12-23 | 2012-03-07 | Voyager Pharmaceutical Corporation | Acetylcholinesterase Inhibitors and leuprolide acetate for the treatment of Alzheimer's disease |
| EP1831172B1 (en) | 2004-12-28 | 2009-02-18 | Council of Scientific and Industrial Research | Substituted carbamic acid quinolin-6-yl esters useful as acetylcholinesterase inhibitors |
| AU2005325930B2 (en) * | 2005-01-27 | 2012-01-19 | Alembic Limited | Extended release formulation of Levetiracetam |
| FR2881618B1 (fr) | 2005-02-10 | 2007-04-13 | Centre Nat Rech Scient | Utilisation de composes derives de pyrimidinetrione en tant qu'inhibiteurs de l'acetylcholinesterase, compositions contenant ces derives et leurs utilisations en tant qu'insecticides |
| US20070298098A1 (en) | 2005-02-16 | 2007-12-27 | Elan Pharma International Limited | Controlled Release Compositions Comprising Levetiracetam |
| ES2403069T3 (es) * | 2005-02-22 | 2013-05-13 | Sun Pharma Advanced Research Company Ltd | Composición oral de liberación controlada que contiene levetiracetam |
| WO2006102750A1 (en) | 2005-03-30 | 2006-10-05 | Genpharm Inc. | Combined-step process for pharmaceutical compositions |
| US20060241144A1 (en) | 2005-04-20 | 2006-10-26 | Albert Cha | Method for treating apathy syndrome |
| EP1890700A2 (en) | 2005-05-31 | 2008-02-27 | Orexigen Therapeutics, Inc. | Methods and compositions for managing psychotic disorders |
| EP1731149A1 (en) | 2005-06-08 | 2006-12-13 | Ucb S.A. | Use of 2-oxo-1-pyrrolidone derivatives for the treatment of diseases characterized by progressive myoclonic epilepsy |
| PL1909764T3 (pl) | 2005-07-26 | 2015-03-31 | Ucb Pharma Sa | Kompozycje farmaceutyczne zawierające lewetyracetam i sposób ich wytwarzania |
| EP1924712B1 (en) | 2005-08-03 | 2018-10-03 | The Johns Hopkins University | Methods for characterizing and treating cognitive impairment in aging and disease |
| GB0517740D0 (en) | 2005-08-31 | 2005-10-12 | Novartis Ag | Organic compounds |
| CA2643199A1 (en) | 2006-03-08 | 2007-09-13 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| WO2007107846A1 (en) | 2006-03-20 | 2007-09-27 | Council Of Scientific And Industrial Research | A pharmaceutical composition useful as acetyl cholinesterase inhibitors |
| CA2650711A1 (en) | 2006-04-28 | 2007-11-08 | Northwestern University | Compositions and treatments using pyridazine compounds and cholinesterase inhibitors |
| US7858611B2 (en) | 2006-05-09 | 2010-12-28 | Braincells Inc. | Neurogenesis by modulating angiotensin |
| US7678808B2 (en) | 2006-05-09 | 2010-03-16 | Braincells, Inc. | 5 HT receptor mediated neurogenesis |
| US8572930B2 (en) | 2006-06-05 | 2013-11-05 | Worthington Armstrong Venture | Single layered web beam for a drywall suspended ceiling |
| EP2041084B1 (en) | 2006-06-08 | 2013-11-06 | UCB Pharma, S.A. | Co-crystals of pyrrolidinones |
| EP2051696A2 (en) | 2006-08-18 | 2009-04-29 | Morton Grove Pharmaceuticals, Inc. | Stable liquid levetiracetam compositions and methods |
| AU2007299726A1 (en) | 2006-09-22 | 2008-03-27 | Braincells, Inc. | Combination comprising an HMG-COA reductase inhibitor and a second neurogenic agent for treating a nervous system disorder and increasing neurogenesis |
| EP2420235A1 (en) | 2006-10-27 | 2012-02-22 | Medivation Neurology, Inc. | Methods and combination therapies for treating alzheimer's disease |
| RU2478619C2 (ru) | 2006-12-11 | 2013-04-10 | Ривайва Фармасьютикалс, Инк. | Композиции, синтез и способы применения ингибиторов холинэстеразы на основе инданона |
| WO2008074896A1 (en) | 2006-12-21 | 2008-06-26 | Prendergast Patrick T | Compositions and methods for treatment of chronic neurological disorders |
| US8101782B2 (en) | 2007-02-02 | 2012-01-24 | Colucid Pharmaceuticals, Inc. | Compounds that inhibit cholinesterase |
| FR2912056B1 (fr) | 2007-02-05 | 2009-12-18 | Rd Pharmagal | Composition a liberation prolongee de levetiracetam et procede de preparation |
| WO2008095221A1 (en) | 2007-02-07 | 2008-08-14 | Gosforth Centre (Holdings) Pty Ltd | Treatment of adhd |
| WO2008144305A1 (en) | 2007-05-18 | 2008-11-27 | Janssen Pharmaceutica N.V. | Diaryl-substituted tetrahydroisoquinolines as histamine h3 receptor and serotonin transporter modulators |
| RU2339620C1 (ru) | 2007-07-09 | 2008-11-27 | Общество С Ограниченной Ответственностью "Фармвинг" | Оксалат n, n-диметил-2-n, n-диметиламинометилпиридил-3-карбамат, обладающий антихолинэстеразной активностью и способностью улучшать когнитивные функции |
| US20100168174A1 (en) | 2007-07-13 | 2010-07-01 | Eisai R&D Management Co., Ltd. | Combination of AMPA Receptor Antagonists and Acetylcholinesterase Inhibitors for the Treatment of Neuropathic Pain |
| US20090030403A1 (en) * | 2007-07-27 | 2009-01-29 | Leyde Kent W | Methods and Systems for Attenuating the Tolerance Response to a Drug |
| WO2009038412A2 (en) | 2007-09-21 | 2009-03-26 | Lg Life Sciences, Ltd. | Beta-secretase inhibiting compounds |
| US20090176740A1 (en) | 2007-11-30 | 2009-07-09 | Phillips Ii Dauglas James | Treatment of neurological conditions by the co-administration of aniracetam and l-alpha glycerylphosphorylcholine |
| EP2254577A1 (en) | 2007-12-26 | 2010-12-01 | Eisai R&D Management Co., Ltd. | Ampa receptor antagonists for epilepsy, mental disorders or deficits in sensory organ |
| DK2273975T3 (da) | 2008-03-03 | 2014-06-30 | Ucb Pharma Sa | Farmaceutiske opløsninger, fremgangsmåde til fremstilling og terapeutiske anvendelser |
| JP2010024156A (ja) | 2008-07-16 | 2010-02-04 | Ucb Pharma Sa | レベチラセタムを含む医薬組成物 |
| MX2011001384A (es) | 2008-08-06 | 2011-09-27 | Gosforth Ct Holdings Pty Ltd | Composiciones y metodos para tratar trastornos psiquiatricos. |
| EP2346500B1 (en) | 2008-10-16 | 2017-05-17 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| US9125898B2 (en) | 2008-11-14 | 2015-09-08 | Neurotune Ag | Acetam derivatives for pain relief |
| WO2010057088A2 (en) | 2008-11-17 | 2010-05-20 | Auspex Pharmaceuticals, Inc. | Pyrrolidinyl modulators of nicotinic acetylcholine receptors |
| KR101689688B1 (ko) | 2008-11-18 | 2016-12-26 | 유씨비 파마, 에스.에이. | ２옥소１피롤리딘 유도체를 포함하는 지연 방출형 제형 |
| US20100172979A1 (en) | 2008-12-24 | 2010-07-08 | Zhongshui Yu | Controlled-release formulations |
| AU2010209790B2 (en) | 2009-01-29 | 2014-01-16 | Ucb Pharma, S.A. | Pharmaceutical compositions comprising 2-oxo-1-pyrrolidine derivatives |
| EP2393483B1 (en) | 2009-02-09 | 2017-06-28 | UCB Biopharma SPRL | Pharmaceutical compositions comprising brivaracetam |
| US8563583B2 (en) | 2009-03-09 | 2013-10-22 | Bristol-Myers Squibb Company | Pyridone analogs useful as melanin concentrating hormone receptor-1 antagonists |
| WO2011015349A2 (en) | 2009-08-07 | 2011-02-10 | Ucb Pharma, S.A. | Methods for enhancing the cognitive function |
| CN101647789B (zh) | 2009-09-01 | 2011-08-17 | 天津药物研究院药业有限责任公司 | 左乙拉西坦缓释微丸胶囊制剂 |
| EP2486918A4 (en) | 2009-10-09 | 2014-02-26 | Yungjin Pharmaceutical Co Ltd | PHARMACEUTICAL COMPOSITION WITH BOTH IMMEDIATE AND DELAYED RELEASE |
| US20110262442A1 (en) | 2009-11-06 | 2011-10-27 | Adenios, Inc. | Compositions for treating cns disorders |
| EP2533645B1 (en) | 2010-02-09 | 2016-07-27 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| WO2011143721A1 (en) | 2010-05-21 | 2011-11-24 | Gosforth Centre (Holdings) Pty Ltd | Compositions and methods for treating neurodegenerative disorders |
| WO2012073146A1 (en) | 2010-12-01 | 2012-06-07 | Pfizer Inc. | Kat ii inhibitors |
| EP2672822A4 (en) | 2011-02-09 | 2014-08-27 | Univ Johns Hopkins | METHOD AND COMPOSITIONS FOR IMPROVING COGNITIVE FUNCTIONS |
| GB201111712D0 (en) | 2011-07-08 | 2011-08-24 | Gosforth Ct Holdings Pty Ltd | Pharmaceutical compositions |
| CA2877134A1 (en) * | 2012-08-08 | 2014-02-13 | PharmTak, Inc. | Extended-release levetiracetam and method of preparation |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| WO2014144546A1 (en) | 2013-03-15 | 2014-09-18 | The Johns Hopkins University | Methods and compositons for improving cognitive function |
| CA2904767C (en) | 2013-03-15 | 2022-06-21 | Agenebio, Inc. | Methods and compositions for improving cognitive function |
| US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| CN104586806B (zh) * | 2014-12-26 | 2018-03-13 | 东北制药集团沈阳第一制药有限公司 | 一种左乙拉西坦缓释片及其制备方法 |
| EA034167B8 (ru) | 2015-05-22 | 2021-04-27 | Эйджинбайо, Инк. | Фармацевтические композиции леветирацетама пролонгированного высвобождения |
-
2016
- 2016-05-20 EA EA201792575A patent/EA034167B8/ru not_active IP Right Cessation
- 2016-05-20 US US15/160,424 patent/US10159648B2/en active Active
- 2016-05-20 CA CA2986598A patent/CA2986598C/en active Active
- 2016-05-20 NZ NZ738682A patent/NZ738682A/en unknown
- 2016-05-20 WO PCT/US2016/033567 patent/WO2016191288A1/en not_active Ceased
- 2016-05-20 AU AU2016268096A patent/AU2016268096B2/en active Active
- 2016-05-20 CN CN202011470929.2A patent/CN112843005B/zh active Active
- 2016-05-20 JP JP2017560719A patent/JP6899043B2/ja active Active
- 2016-05-20 MX MX2017014774A patent/MX384391B/es unknown
- 2016-05-20 HK HK18111302.0A patent/HK1251980B/en unknown
- 2016-05-20 CN CN201680037483.XA patent/CN107810002B/zh active Active
- 2016-05-20 US US15/574,824 patent/US10925834B2/en active Active
- 2016-05-20 BR BR112017025031-4A patent/BR112017025031B1/pt active IP Right Grant
-
2017
- 2017-11-17 MX MX2021008289A patent/MX2021008289A/es unknown
- 2017-11-20 IL IL255782A patent/IL255782B/en active IP Right Grant
- 2017-12-20 ZA ZA2017/08703A patent/ZA201708703B/en unknown
-
2020
- 2020-08-24 JP JP2020140683A patent/JP2020186275A/ja not_active Withdrawn
- 2020-08-24 JP JP2020140682A patent/JP7093907B2/ja active Active
- 2020-09-17 ZA ZA2020/05768A patent/ZA202005768B/en unknown
- 2020-10-08 IL IL277872A patent/IL277872B/en unknown
- 2020-12-17 US US17/125,737 patent/US20210346299A1/en not_active Abandoned
-
2021
- 2021-06-29 AU AU2021204465A patent/AU2021204465B2/en active Active
- 2021-10-24 IL IL287520A patent/IL287520A/en unknown
-
2022
- 2022-05-20 JP JP2022082954A patent/JP2022103412A/ja active Pending
- 2022-07-06 US US17/858,405 patent/US20230172862A1/en not_active Abandoned
- 2022-08-25 AU AU2022221476A patent/AU2022221476A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008006528A2 (en) * | 2006-07-13 | 2008-01-17 | Ucb Pharma, S.A. | Pharmaceutical compositions comprising levetiracetam |
| WO2008062446A2 (en) * | 2006-09-14 | 2008-05-29 | Alembic Limited | An extended release composition of levetiracetam, which exhibits no adverse food effect |
| WO2012070785A1 (en) * | 2010-11-23 | 2012-05-31 | Bio Pharmartis Co., Ltd. | Sustained-release pharmaceutical composition comprising levetiracetam or pharmaceutically acceptable salt thereof having improved dissolution stability and method for manufacturing the same |
| WO2012159609A1 (de) * | 2011-05-26 | 2012-11-29 | Stada Arzneimittel Ag | Pulverförmige mischung zur herstellung von levetiracetam-haltigen tabletten |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107810002B (zh) | 左乙拉西坦的延时释放药物组合物 | |
| CN105744932B (zh) | 用于治疗神经障碍的包含托拉塞米和巴氯芬的组合物 | |
| EP2167095B1 (en) | Phenothiazine compounds for treating mild cognitive impairment | |
| CN109890391A (zh) | 痴呆症的治疗 | |
| CN104884053B (zh) | 用于改善记忆表现的益智组合物 | |
| CN116075302A (zh) | GABAAα5激动剂和SV2A抑制剂的组合以及在认知损害的治疗中的使用方法 | |
| CN109069450A (zh) | 神经障碍的新的组合疗法 | |
| EP3297611B1 (en) | Extended release pharmaceutical compositions of levetiracetam | |
| HK40052880A (en) | Extended release pharmaceutical compositions of levetiracetam | |
| TW202038955A (zh) | 用於治療多巴胺性cns病症之ly3154207劑量療法 | |
| HK40018277A (en) | Extended release pharmaceutical compositions of levetiracetam | |
| HK1252154B (en) | Extended release pharmaceutical compositions of levetiracetam | |
| OA18467A (en) | Extended release pharmaceutical compositions of levetiracetam | |
| CN119562810A (zh) | 用于减少帕金森氏病进展的沃多巴替尼 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40052880 Country of ref document: HK |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |