TW201804997A - 高劑量拉喹莫德(laquinimod)於治療多發性硬化症之用途 - Google Patents
高劑量拉喹莫德(laquinimod)於治療多發性硬化症之用途 Download PDFInfo
- Publication number
- TW201804997A TW201804997A TW106117959A TW106117959A TW201804997A TW 201804997 A TW201804997 A TW 201804997A TW 106117959 A TW106117959 A TW 106117959A TW 106117959 A TW106117959 A TW 106117959A TW 201804997 A TW201804997 A TW 201804997A
- Authority
- TW
- Taiwan
- Prior art keywords
- drug
- laquinimod
- patient
- multiple sclerosis
- score
- Prior art date
Links
- GKWPCEFFIHSJOE-UHFFFAOYSA-N laquinimod Chemical compound OC=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 GKWPCEFFIHSJOE-UHFFFAOYSA-N 0.000 title claims abstract description 216
- 229960004577 laquinimod Drugs 0.000 title claims abstract description 209
- 201000006417 multiple sclerosis Diseases 0.000 title claims abstract description 140
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 206010061818 Disease progression Diseases 0.000 claims abstract description 40
- 230000005750 disease progression Effects 0.000 claims abstract description 40
- 208000024806 Brain atrophy Diseases 0.000 claims abstract description 34
- 239000002552 dosage form Substances 0.000 claims abstract description 26
- 239000003937 drug carrier Substances 0.000 claims abstract description 15
- 230000004112 neuroprotection Effects 0.000 claims abstract description 12
- 206010071068 Clinically isolated syndrome Diseases 0.000 claims abstract 5
- 239000003814 drug Substances 0.000 claims description 89
- 238000011282 treatment Methods 0.000 claims description 83
- 229940079593 drug Drugs 0.000 claims description 75
- 230000003902 lesion Effects 0.000 claims description 60
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims description 55
- 230000002829 reductive effect Effects 0.000 claims description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
- 230000002354 daily effect Effects 0.000 claims description 28
- 230000036541 health Effects 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 26
- 208000024891 symptom Diseases 0.000 claims description 23
- 206010016256 fatigue Diseases 0.000 claims description 17
- 238000012360 testing method Methods 0.000 claims description 17
- 108010005716 Interferon beta-1a Proteins 0.000 claims description 16
- 230000009266 disease activity Effects 0.000 claims description 16
- 239000002775 capsule Substances 0.000 claims description 14
- 210000003169 central nervous system Anatomy 0.000 claims description 13
- 230000009467 reduction Effects 0.000 claims description 13
- 208000010877 cognitive disease Diseases 0.000 claims description 12
- 208000028698 Cognitive impairment Diseases 0.000 claims description 10
- 229960005027 natalizumab Drugs 0.000 claims description 10
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- 108010072051 Glatiramer Acetate Proteins 0.000 claims description 9
- 108010005714 Interferon beta-1b Proteins 0.000 claims description 9
- 230000006866 deterioration Effects 0.000 claims description 9
- 229960000556 fingolimod Drugs 0.000 claims description 9
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 claims description 9
- 238000001990 intravenous administration Methods 0.000 claims description 9
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 9
- 238000009825 accumulation Methods 0.000 claims description 8
- 229960004461 interferon beta-1a Drugs 0.000 claims description 8
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 claims description 7
- 229960003776 glatiramer acetate Drugs 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 229960003161 interferon beta-1b Drugs 0.000 claims description 7
- 229960001156 mitoxantrone Drugs 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 5
- 230000006764 neuronal dysfunction Effects 0.000 claims description 5
- 230000003961 neuronal insult Effects 0.000 claims description 5
- 150000003431 steroids Chemical class 0.000 claims description 5
- 230000001629 suppression Effects 0.000 claims description 5
- 230000006872 improvement Effects 0.000 claims description 4
- 238000012544 monitoring process Methods 0.000 claims description 4
- 230000019581 neuron apoptotic process Effects 0.000 claims description 4
- 238000012790 confirmation Methods 0.000 claims description 3
- 238000009097 single-agent therapy Methods 0.000 claims description 3
- 230000004630 mental health Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 230000003203 everyday effect Effects 0.000 claims 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 44
- 238000002595 magnetic resonance imaging Methods 0.000 description 52
- 235000002639 sodium chloride Nutrition 0.000 description 38
- 229940068196 placebo Drugs 0.000 description 36
- 239000000902 placebo Substances 0.000 description 36
- 238000012216 screening Methods 0.000 description 17
- 230000008859 change Effects 0.000 description 16
- 230000009850 completed effect Effects 0.000 description 16
- 210000004556 brain Anatomy 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 12
- 230000000926 neurological effect Effects 0.000 description 12
- 238000011160 research Methods 0.000 description 12
- 238000011161 development Methods 0.000 description 11
- 230000018109 developmental process Effects 0.000 description 11
- 210000001428 peripheral nervous system Anatomy 0.000 description 10
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 230000001186 cumulative effect Effects 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000007937 lozenge Substances 0.000 description 8
- 230000005415 magnetization Effects 0.000 description 8
- 230000006870 function Effects 0.000 description 7
- 230000005856 abnormality Effects 0.000 description 6
- 229940003504 avonex Drugs 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 5
- 238000007918 intramuscular administration Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 206010003694 Atrophy Diseases 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 102100026720 Interferon beta Human genes 0.000 description 4
- 108090000467 Interferon-beta Proteins 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 230000037444 atrophy Effects 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 230000003920 cognitive function Effects 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 230000003862 health status Effects 0.000 description 4
- 229940079322 interferon Drugs 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 4
- 235000015424 sodium Nutrition 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- 206010003591 Ataxia Diseases 0.000 description 3
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 3
- 108010010803 Gelatin 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
- 206010061218 Inflammation Diseases 0.000 description 3
- 102000006386 Myelin Proteins Human genes 0.000 description 3
- 108010083674 Myelin Proteins Proteins 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 235000010419 agar Nutrition 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 229960002436 cladribine Drugs 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 239000000411 inducer Substances 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 210000005012 myelin Anatomy 0.000 description 3
- 230000023105 myelination Effects 0.000 description 3
- 230000003557 neuropsychological effect Effects 0.000 description 3
- 208000035824 paresthesia Diseases 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 230000009747 swallowing Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 229940079023 tysabri Drugs 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 206010051290 Central nervous system lesion Diseases 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 2
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 2
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 206010012305 Demyelination Diseases 0.000 description 2
- 206010067671 Disease complication Diseases 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 102000003996 Interferon-beta Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 230000007844 axonal damage Effects 0.000 description 2
- 229960003270 belimumab Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 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 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 238000011976 chest X-ray Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000003433 contraceptive agent Substances 0.000 description 2
- 230000002254 contraceptive effect Effects 0.000 description 2
- 229940038717 copaxone Drugs 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- -1 cycadine Polymers 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 239000002254 cytotoxic agent Substances 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000024924 glomerular filtration Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229960001388 interferon-beta Drugs 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 238000009533 lab test Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 230000027939 micturition Effects 0.000 description 2
- 238000002610 neuroimaging Methods 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229950005751 ocrelizumab Drugs 0.000 description 2
- 229960002450 ofatumumab Drugs 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 229940126701 oral medication Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 229940038850 rebif Drugs 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 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
- 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
- MISZALMBODQYFT-URVXVIKDSA-N 125-69-9 Chemical compound Br.C([C@@H]12)CCC[C@]11CCN(C)[C@H]2CC2=CC=C(OC)C=C21 MISZALMBODQYFT-URVXVIKDSA-N 0.000 description 1
- SGOOQMRIPALTEL-UHFFFAOYSA-N 4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-3-quinolinecarboxamide Chemical compound OC=1C2=CC=CC=C2N(C)C(=O)C=1C(=O)N(C)C1=CC=CC=C1 SGOOQMRIPALTEL-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 208000007848 Alcoholism Diseases 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
- 239000004382 Amylase Substances 0.000 description 1
- 102000013142 Amylases Human genes 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000037187 Autoimmune Experimental Neuritis Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000022306 Cerebral injury Diseases 0.000 description 1
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 1
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010010947 Coordination abnormal Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- DSRJIHMZAQEUJV-UHFFFAOYSA-N Cuprizon Chemical compound C1CCCCC1=NNC(=O)C(=O)NN=C1CCCCC1 DSRJIHMZAQEUJV-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 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
- 241001166076 Diapheromera femorata Species 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 208000003164 Diplopia Diseases 0.000 description 1
- 238000008789 Direct Bilirubin Methods 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010015108 Epstein-Barr virus infection Diseases 0.000 description 1
- 206010016059 Facial pain Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 102100040485 HLA class II histocompatibility antigen, DRB1 beta chain Human genes 0.000 description 1
- 108010039343 HLA-DRB1 Chains Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010021639 Incontinence Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010053395 Progressive multiple sclerosis Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000220010 Rhode Species 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 206010071299 Slow speech Diseases 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 108700002718 TACI receptor-IgG Fc fragment fusion Proteins 0.000 description 1
- 206010057040 Temperature intolerance Diseases 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 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
- 230000004913 activation Effects 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000019418 amylase Nutrition 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 230000003140 astrocytic effect Effects 0.000 description 1
- 229950009925 atacicept Drugs 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229940021459 betaseron Drugs 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000005978 brain dysfunction Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000002597 diffusion-weighted imaging Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 1
- 229960004419 dimethyl fumarate Drugs 0.000 description 1
- 238000011979 disease modifying therapy Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 208000029444 double vision Diseases 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000008543 heat sensitivity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 208000028756 lack of coordination Diseases 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000011694 lewis rat Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 238000010234 longitudinal analysis Methods 0.000 description 1
- 208000018883 loss of balance Diseases 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000004066 metabolic change Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000001617 migratory effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 230000009223 neuronal apoptosis Effects 0.000 description 1
- 230000000324 neuroprotective 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
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 208000022821 personality disease Diseases 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000002974 pharmacogenomic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000013105 post hoc analysis Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000013442 quality metrics Methods 0.000 description 1
- 230000004461 rapid eye movement Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 229960003522 roquinimex Drugs 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 208000026473 slurred speech Diseases 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 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
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- JWHPPWBIIQMBQC-UHFFFAOYSA-M sodium;5-chloro-3-[ethyl(phenyl)carbamoyl]-1-methyl-2-oxoquinolin-4-olate Chemical compound [Na+].[O-]C=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 JWHPPWBIIQMBQC-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000934 spermatocidal agent Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000009168 stem cell therapy Methods 0.000 description 1
- 238000009580 stem-cell therapy Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960000331 teriflunomide Drugs 0.000 description 1
- UTNUDOFZCWSZMS-YFHOEESVSA-N teriflunomide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(C(F)(F)F)C=C1 UTNUDOFZCWSZMS-YFHOEESVSA-N 0.000 description 1
- 230000000542 thalamic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 201000002282 venous insufficiency Diseases 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4704—2-Quinolinones, e.g. carbostyril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P25/28—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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261641389P | 2012-05-02 | 2012-05-02 | |
| US61/641,389 | 2012-05-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW201804997A true TW201804997A (zh) | 2018-02-16 |
Family
ID=49514859
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW106117959A TW201804997A (zh) | 2012-05-02 | 2013-04-29 | 高劑量拉喹莫德(laquinimod)於治療多發性硬化症之用途 |
| TW102115308A TW201347762A (zh) | 2012-05-02 | 2013-04-29 | 高劑量拉喹莫德（ｌａｑｕｉｎｉｍｏｄ）於治療多發性硬化症之用途 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102115308A TW201347762A (zh) | 2012-05-02 | 2013-04-29 | 高劑量拉喹莫德（ｌａｑｕｉｎｉｍｏｄ）於治療多發性硬化症之用途 |
Country Status (21)
| Country | Link |
|---|---|
| US (3) | US20130303569A1 (enExample) |
| EP (1) | EP2844255A4 (enExample) |
| JP (2) | JP2015515985A (enExample) |
| KR (1) | KR20150013658A (enExample) |
| CN (2) | CN104284663A (enExample) |
| AR (1) | AR090885A1 (enExample) |
| AU (1) | AU2013256352A1 (enExample) |
| BR (1) | BR112014027010A2 (enExample) |
| CA (1) | CA2870684A1 (enExample) |
| CL (1) | CL2014002935A1 (enExample) |
| EA (1) | EA201492010A1 (enExample) |
| HK (1) | HK1206246A1 (enExample) |
| IL (1) | IL235337A0 (enExample) |
| MX (1) | MX2014013039A (enExample) |
| PE (1) | PE20150161A1 (enExample) |
| PH (1) | PH12014502447A1 (enExample) |
| SG (1) | SG11201406594UA (enExample) |
| TW (2) | TW201804997A (enExample) |
| UY (1) | UY34775A (enExample) |
| WO (1) | WO2013166166A1 (enExample) |
| ZA (1) | ZA201408820B (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014530821A (ja) | 2011-10-12 | 2014-11-20 | テバ ファーマシューティカル インダストリーズ リミティド | ラキニモドおよびフィンゴリモドを組み合わせた多発性硬化症の治療 |
| JP2015505564A (ja) | 2012-02-03 | 2015-02-23 | テバ ファーマシューティカル インダストリーズ リミティド | 第一選択の抗ＴＮＥα療法に失敗したクローン病患者を治療するためのラキニモドの使用 |
| EP3225617A1 (en) | 2012-02-16 | 2017-10-04 | Teva Pharmaceutical Industries Ltd | N-ethyl-n-phenyl-1,2-dihydro-4,5-di-hydroxy-1-methyl-2-oxo-3-quinoline carboxamide, preparation and uses thereof |
| US20130259856A1 (en) * | 2012-03-27 | 2013-10-03 | Teva Pharmaceutical Industries, Ltd. | Treatment of multiple sclerosis with combination of laquinimod and dimethyl fumarate |
| TW201400117A (zh) | 2012-06-05 | 2014-01-01 | Teva Pharma | 使用拉喹莫德治療眼發炎疾病 |
| TW201410244A (zh) | 2012-08-13 | 2014-03-16 | Teva Pharma | 用於治療ｇａｂａ媒介之疾病之拉喹莫德（ｌａｑｕｉｎｉｍｏｄ） |
| JP2015533163A (ja) * | 2012-10-12 | 2015-11-19 | テバ ファーマシューティカル インダストリーズ リミティド | 多発性硬化症における視床損傷を低減するためのラキニモド |
| EA201590788A1 (ru) | 2012-11-07 | 2015-12-30 | Тева Фармасьютикал Индастриз Лтд. | Аминные соли лахинимода |
| HK1218254A1 (zh) * | 2013-02-15 | 2017-02-10 | Teva Pharmaceutical Industries Ltd. | 用拉喹莫德治疗多发性硬化症 |
| HK1220444A1 (zh) | 2013-03-14 | 2017-05-05 | Teva Pharmaceutical Industries Ltd. | 拉喹莫德钠晶体和用於制造它们的改进方法 |
| AR098924A1 (es) * | 2013-12-23 | 2016-06-22 | Teva Pharma | Tratamiento de la esclerosis múltiple con una combinación de laquinimod y teriflunomida |
| EA201692180A1 (ru) * | 2014-04-29 | 2017-08-31 | Тева Фармасьютикал Индастриз Лтд. | Лахинимод для лечения пациентов с рецидивирующе-ремиттирующим рассеянным склерозом (рррс) с высоким статусом инвалидизации |
| WO2017027512A1 (en) * | 2015-08-13 | 2017-02-16 | Teva Pharmaceutical Industries Ltd. | Use of laquinimod to treat traumatic brain injury |
| US20190108912A1 (en) * | 2017-10-05 | 2019-04-11 | Iquity, Inc. | Methods for predicting or detecting disease |
| FI3823623T3 (fi) * | 2018-07-20 | 2025-01-09 | Merck Patent Gmbh | Substituoitu aminopyrimidiiniyhdiste käytettäväksi pesäkekovettumataudin hoito- ja ehkäisymenetelmässä |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6077851A (en) * | 1998-04-27 | 2000-06-20 | Active Biotech Ab | Quinoline derivatives |
| HRP20160455T1 (hr) * | 2004-09-09 | 2016-07-15 | Yeda Research And Development Co., Ltd. | Smjese polipeptida, sastavi koji ih sadrže i postupci za njihovu pripremu, te njihove primjene |
| WO2007146331A1 (en) * | 2006-06-12 | 2007-12-21 | Teva Pharmaceutical Industries, Ltd. | Tannate salt form of polypeptide mixtures, their preparation and use |
| PT2442651E (pt) * | 2009-06-19 | 2015-10-22 | Teva Pharma | Tratamento da esclerose múltipla com laquinimod |
| WO2011086470A1 (en) * | 2010-01-13 | 2011-07-21 | Ramot At Tel-Aviv University Ltd | Treatment of multiple sclerosis |
| JP2014530821A (ja) * | 2011-10-12 | 2014-11-20 | テバ ファーマシューティカル インダストリーズ リミティド | ラキニモドおよびフィンゴリモドを組み合わせた多発性硬化症の治療 |
| HK1218254A1 (zh) * | 2013-02-15 | 2017-02-10 | Teva Pharmaceutical Industries Ltd. | 用拉喹莫德治疗多发性硬化症 |
-
2013
- 2013-04-29 TW TW106117959A patent/TW201804997A/zh unknown
- 2013-04-29 AR ARP130101459A patent/AR090885A1/es unknown
- 2013-04-29 TW TW102115308A patent/TW201347762A/zh unknown
- 2013-04-30 UY UY0001034775A patent/UY34775A/es not_active Application Discontinuation
- 2013-05-01 SG SG11201406594UA patent/SG11201406594UA/en unknown
- 2013-05-01 KR KR1020147033707A patent/KR20150013658A/ko not_active Withdrawn
- 2013-05-01 MX MX2014013039A patent/MX2014013039A/es unknown
- 2013-05-01 CA CA2870684A patent/CA2870684A1/en not_active Abandoned
- 2013-05-01 WO PCT/US2013/039090 patent/WO2013166166A1/en not_active Ceased
- 2013-05-01 BR BR112014027010A patent/BR112014027010A2/pt not_active IP Right Cessation
- 2013-05-01 CN CN201380022530.XA patent/CN104284663A/zh active Pending
- 2013-05-01 US US13/874,537 patent/US20130303569A1/en not_active Abandoned
- 2013-05-01 PE PE2014001911A patent/PE20150161A1/es not_active Application Discontinuation
- 2013-05-01 CN CN201610240473.8A patent/CN105832733A/zh active Pending
- 2013-05-01 EA EA201492010A patent/EA201492010A1/ru unknown
- 2013-05-01 AU AU2013256352A patent/AU2013256352A1/en not_active Abandoned
- 2013-05-01 HK HK15106789.5A patent/HK1206246A1/xx unknown
- 2013-05-01 JP JP2015510436A patent/JP2015515985A/ja not_active Withdrawn
- 2013-05-01 EP EP13784231.6A patent/EP2844255A4/en not_active Withdrawn
-
2014
- 2014-10-26 IL IL235337A patent/IL235337A0/en unknown
- 2014-10-29 CL CL2014002935A patent/CL2014002935A1/es unknown
- 2014-10-31 PH PH12014502447A patent/PH12014502447A1/en unknown
- 2014-12-02 ZA ZA2014/08820A patent/ZA201408820B/en unknown
-
2015
- 2015-06-05 US US14/731,971 patent/US20150265592A1/en not_active Abandoned
- 2015-09-15 US US14/854,849 patent/US20160000775A1/en not_active Abandoned
-
2017
- 2017-07-21 JP JP2017141409A patent/JP2017222691A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| IL235337A0 (en) | 2014-12-31 |
| US20130303569A1 (en) | 2013-11-14 |
| US20160000775A1 (en) | 2016-01-07 |
| ZA201408820B (en) | 2016-06-29 |
| EP2844255A1 (en) | 2015-03-11 |
| US20150265592A1 (en) | 2015-09-24 |
| SG11201406594UA (en) | 2014-11-27 |
| JP2015515985A (ja) | 2015-06-04 |
| JP2017222691A (ja) | 2017-12-21 |
| EA201492010A1 (ru) | 2015-06-30 |
| TW201347762A (zh) | 2013-12-01 |
| EP2844255A4 (en) | 2015-10-14 |
| HK1206246A1 (en) | 2016-01-08 |
| CL2014002935A1 (es) | 2015-03-06 |
| PH12014502447A1 (en) | 2015-01-12 |
| UY34775A (es) | 2013-11-29 |
| MX2014013039A (es) | 2015-02-04 |
| CN104284663A (zh) | 2015-01-14 |
| CA2870684A1 (en) | 2013-11-07 |
| AR090885A1 (es) | 2014-12-10 |
| WO2013166166A1 (en) | 2013-11-07 |
| PE20150161A1 (es) | 2015-02-22 |
| AU2013256352A1 (en) | 2014-11-27 |
| CN105832733A (zh) | 2016-08-10 |
| KR20150013658A (ko) | 2015-02-05 |
| BR112014027010A2 (pt) | 2017-06-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW201804997A (zh) | 高劑量拉喹莫德(laquinimod)於治療多發性硬化症之用途 | |
| DK2442651T3 (en) | Treatment of multiple sclerosis with laquinimod | |
| JP2017095476A (ja) | 多発性硬化症患者において疲労を軽減し、機能状態を改善し、生活の質を改善するための、ラキニモド（ｌａｑｕｉｎｉｍｏｄ）の使用 | |
| JP2017061482A (ja) | ラキニモドおよびインターフェロンβを組み合わせた多発性硬化症の治療 | |
| US20160296511A1 (en) | Laquinimod for reducing thalamic damage in multiple sclerosis | |
| US20180064702A1 (en) | Treatment of progressive forms of multiple sclerosis with laquinimod | |
| US20170151224A1 (en) | Laquinimod for the treatment of relapsing-remitting multiple sclerosis (rrms) patients with a high disability status | |
| TW201408300A (zh) | 以拉喹莫德（ｌａｑｕｉｎｉｍｏｄ）及氨吡啶（ｆａｍｐｒｉｄｉｎｅ）之組合治療多發性硬化症 | |
| HK1224555A1 (en) | Use of high dose laquinimod for treating multiple sclerosis | |
| TW201404395A (zh) | 以拉喹莫德（ｌａｑｕｉｎｉｍｏｄ）及醋酸格拉替雷（ｇｌａｔｉｒａｍｅｒ ａｃｅｔａｔｅ）之組合治療多發性硬化症 |