WO2024096445A1 - Composition for ameliorating, preventing, or treating stress and depression-related diseases, comprising talampanel - Google Patents
Composition for ameliorating, preventing, or treating stress and depression-related diseases, comprising talampanel Download PDFInfo
- Publication number
- WO2024096445A1 WO2024096445A1 PCT/KR2023/016806 KR2023016806W WO2024096445A1 WO 2024096445 A1 WO2024096445 A1 WO 2024096445A1 KR 2023016806 W KR2023016806 W KR 2023016806W WO 2024096445 A1 WO2024096445 A1 WO 2024096445A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- stress
- depression
- talampanel
- related diseases
- acceptable salt
- Prior art date
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 52
- 201000010099 disease Diseases 0.000 title claims abstract description 46
- JACAAXNEHGBPOQ-LLVKDONJSA-N Talampanel Chemical compound C([C@H](N(N=1)C(C)=O)C)C2=CC=3OCOC=3C=C2C=1C1=CC=C(N)C=C1 JACAAXNEHGBPOQ-LLVKDONJSA-N 0.000 title claims abstract description 42
- 229950004608 talampanel Drugs 0.000 title claims abstract description 41
- 239000000203 mixture Substances 0.000 title claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 235000013305 food Nutrition 0.000 claims description 18
- 230000000694 effects Effects 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 7
- 206010022437 insomnia Diseases 0.000 claims description 7
- 208000006561 Cluster Headache Diseases 0.000 claims description 6
- 208000019695 Migraine disease Diseases 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- 208000010877 cognitive disease Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- 238000009825 accumulation Methods 0.000 claims description 5
- 230000003252 repetitive effect Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 208000028698 Cognitive impairment Diseases 0.000 claims 5
- 206010027175 memory impairment Diseases 0.000 claims 5
- 230000001430 anti-depressive effect Effects 0.000 abstract description 6
- 239000000935 antidepressant agent Substances 0.000 abstract description 6
- 229940005513 antidepressants Drugs 0.000 abstract description 5
- 230000002180 anti-stress Effects 0.000 abstract description 3
- 230000035882 stress Effects 0.000 description 43
- 238000012360 testing method Methods 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- -1 Inorganic acid salts Chemical class 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- 238000012048 forced swim test Methods 0.000 description 7
- 238000010172 mouse model Methods 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 241000700159 Rattus Species 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 206010010144 Completed suicide Diseases 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000037326 chronic stress Effects 0.000 description 4
- 235000013376 functional food Nutrition 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 230000009182 swimming Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 239000007844 bleaching agent Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000000994 depressogenic effect Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000007415 Anhedonia Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-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
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011572 manganese Substances 0.000 description 2
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 2
- 235000013923 monosodium glutamate Nutrition 0.000 description 2
- 230000008450 motivation Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-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
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- GGLIEWRLXDLBBF-UHFFFAOYSA-N Dulcin Chemical compound CCOC1=CC=C(NC(N)=O)C=C1 GGLIEWRLXDLBBF-UHFFFAOYSA-N 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102000006541 Ionotropic Glutamate Receptors Human genes 0.000 description 1
- 108010008812 Ionotropic Glutamate Receptors Proteins 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 244000147568 Laurus nobilis Species 0.000 description 1
- 235000017858 Laurus nobilis Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 240000007817 Olea europaea Species 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
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 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
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 208000018912 cluster headache syndrome Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 229940109275 cyclamate Drugs 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007357 depressive behavior Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 210000003027 ear inner Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 description 1
- 230000026781 habituation Effects 0.000 description 1
- 208000029824 high grade glioma Diseases 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 206010021654 increased appetite Diseases 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 201000011614 malignant glioma Diseases 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000003340 mental effect 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 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
- 206010027599 migraine Diseases 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000004223 monosodium glutamate Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229940086065 potassium hydrogentartrate Drugs 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 230000008566 social perception Effects 0.000 description 1
- 229940083542 sodium 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
- 229960003885 sodium benzoate Drugs 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000012453 solvate Substances 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
- 238000005728 strengthening Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- JBQYATWDVHIOAR-UHFFFAOYSA-N tellanylidenegermanium Chemical compound [Te]=[Ge] JBQYATWDVHIOAR-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Chemical class 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Chemical class 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 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
- 229960002675 xylitol Drugs 0.000 description 1
Images
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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- 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
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/30—Other Organic compounds
Definitions
- the present invention relates to a composition containing talampanel for improving, preventing or treating diseases related to stress and depression.
- neuropsychiatric diseases including anxiety, depression, and schizophrenia are on the rise due to rapidly increasing stress.
- the number of patients suffering from stress and depression is increasing due to various causes, including social and structural causes.
- Talampanel acts as a non-competitive antagonist of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, a type of ionotropic glutamate receptor in the central nervous system. It is a drug studied for the treatment of epilepsy, malignant glioma, traumatic brain injury, epilepsy, and amyotrophic lateral sclerosis (ALS).
- AMPA alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- the present inventors confirmed that talampanel can be effectively used to improve and treat stress and depression by confirming the efficacy of talampanel in improving and treating stress and depression in a stress-induced depression model, and completed the present invention.
- the purpose of the present invention is to provide a pharmaceutical composition for preventing or treating diseases related to stress and depression, comprising talampanel or a pharmaceutically acceptable salt thereof represented by the following formula (1).
- the purpose of the present invention is to provide the use of talampanel in the treatment of diseases related to stress and depression.
- the purpose of the present invention is to provide a method of treating stress and depression-related diseases by administering talampanel to an individual in need thereof.
- the present invention provides a pharmaceutical composition for preventing or treating diseases related to stress and depression, comprising talampanel or a pharmaceutically acceptable salt thereof represented by the following formula (1).
- the talampanel has the structure of Formula 1 above.
- Talampanel shows excellent improvement effects on stress and depression-related diseases.
- the stress- and depression-related diseases mentioned above are a concept that includes symptoms in which cognitive, mental, and physical symptoms appear due to loss of motivation and persistent depression, leading to a decline in daily functioning. Stress and depression-related diseases related to the above symptoms, including persistent depression, decreased motivation, sleep disorders such as insomnia, weight changes related to decreased or increased appetite, repeated thoughts or attempts of suicide, negative thinking, excessive guilt, etc. means.
- depression, stress, post-operative stress syndrome cluster headache due to stress, migraine due to stress, unexplained pain due to stress, insomnia due to stress, memory disorder, cognitive disorder, and attention disorder. It could be any one.
- talampanel has excellent antidepressant and anti-stress efficacy in experiments conducted on animal models of stress-induced depression, and thus talampanel is useful for improving and treating diseases related to stress and depression. It was confirmed that it can be used.
- prevention used in the present invention refers to all actions that suppress or delay the onset of diseases related to stress and depression by administering a composition.
- treatment means any action in which the symptoms of the disease are improved or beneficially changed by administration of the composition.
- pharmaceutically acceptable salts refer to salts commonly used in the pharmaceutical industry, such as inorganic ionic salts made of calcium, potassium, sodium, magnesium, etc.; Inorganic acid salts made from hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, iodic acid, perchloric acid and sulfuric acid; Acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid.
- inorganic ionic salts made of calcium, potassium, sodium, magnesium, etc.
- Inorganic acid salts made from hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, iodic acid, perchloric acid and sulfuric acid
- Organic acid salts made from acids, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc.; Sulfonic acid salts made from methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, etc.; Amino acid salts made from glycine, arginine, lysine, etc.; and amine salts prepared from trimethylamine, triethylamine, ammonia, pyridine, picoline, etc., but the types of salts meant in the present invention are not limited by these salts listed.
- talampanel represented by Formula 1 of the present invention includes not only pharmaceutically acceptable salts, but also all salts, hydrates, and solvates that can be prepared by conventional methods.
- the pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier, and may be prepared in oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, etc. according to conventional methods. It may be formulated in the form of a sterile injectable solution.
- the pharmaceutically acceptable carriers include those commonly used in the art, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, Including, but not limited to, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
- the pharmaceutical composition of the present invention may contain diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and other pharmaceutically acceptable additives, but is not limited thereto.
- the pharmaceutical composition of the present invention when formulated as an oral solid preparation, it includes tablets, pills, powders, granules, capsules, etc., and such solid preparations contain at least one excipient, such as starch, calcium carbonate, It may contain sucrose or lactose, gelatin, etc., and includes, but is not limited to, lubricants such as magnesium stearate and talc.
- the pharmaceutical composition of the present invention when formulated in liquid form for oral use, it includes suspensions, oral solutions, emulsions, syrups, etc., and includes, but is not limited to, diluents such as water and liquid paraffin, humectants, sweeteners, fragrances, preservatives, etc.
- the pharmaceutical composition of the present invention when formulated for parenteral use, it includes sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories.
- Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, and olive. Includes, but is not limited to, vegetable oils such as oil, injectable esters such as ethyl oleate, etc.
- As a base for suppositories witepsol, macrogol, tween 61, cacao, laurel, glycerogelatin, etc. can be used, but are not limited to these.
- composition can be administered singly or multiple times in a pharmaceutically effective amount.
- pharmaceutically effective amount of the present invention means an amount sufficient to prevent or treat a disease with a reasonable benefit/risk ratio applicable to medical prevention or treatment, and the effective dose level is determined by the severity of the disease, the activity of the drug, Including the patient's age, weight, health, gender, patient's sensitivity to drugs, administration time, administration route and excretion rate of the composition of the present invention used, treatment period, and drugs mixed or used simultaneously with the composition of the present invention used. It can be determined according to factors well known in the medical field and other factors. For example, the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof can be administered at 0.0001 to 100 mg/kg per day, and the administration may be administered once a day or in divided doses.
- the pharmaceutical composition of the present invention is administered to mammals such as rats, mice, livestock, and humans by various routes, for example, by oral administration, intrathecium, inner ear, abdominal cavity or vein, muscle, subcutaneous, intrauterine dura, sublingual or cerebrovascular administration. It may be administered by injection, but is not limited to this.
- the pharmaceutical composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight, of the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof, based on the total weight of the composition.
- the pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. Additionally, the pharmaceutical composition of the present invention can be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art.
- subject of the present invention includes animals or humans whose symptoms can be improved by administration of the pharmaceutical composition according to the present invention.
- diseases related to stress and depression can be effectively prevented and treated.
- administration means introducing a predetermined substance into a human or animal by any appropriate method, and the route of administration of the therapeutic composition according to the present invention is through any general route as long as it can reach the target tissue. It may be administered orally or parenterally. Additionally, the therapeutic composition according to the present invention can be administered by any device that can move the active ingredient to target cells.
- Another aspect of the present invention is the prevention of stress and depression-related diseases, comprising administering a therapeutically effective amount of the compound represented by Formula 1, or a pharmaceutically acceptable salt thereof, to an individual in need thereof. Or provide a treatment method.
- the term "individual" of the present invention refers to any animal that has developed or can develop diseases related to stress and depression, and is typically treated with a compound represented by Formula 1 of the present invention, or a pharmaceutically acceptable salt thereof. It may be an animal that can show beneficial effects, but any animal that has symptoms of stress or depression-related diseases or is likely to have these symptoms is included without limitation. As described above, the stress- and depression-related diseases can be effectively prevented or treated by administering the pharmaceutical composition of the present invention to an individual.
- Another aspect of the present invention provides the use of the compound represented by Formula 1 of the present invention, or a pharmaceutically acceptable salt thereof, for manufacturing a medicine for preventing or treating diseases related to stress and depression.
- Another aspect of the present invention provides a pharmaceutical composition
- a pharmaceutical composition comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of diseases related to stress and depression.
- the present invention provides a food composition for preventing or improving diseases related to stress and depression, comprising talampanel or a foodologically acceptable salt thereof represented by the following formula (1).
- improvement in the present invention refers to any action in which stress- and depression-related diseases are improved or beneficially changed by administration of the composition of the present invention.
- the talampanel and its salt are preferably contained in an amount of 0.00001 to 0.01% by weight relative to the food composition. If it is less than 0.00001% by weight, the effect is insignificant, and if it exceeds 0.01% by weight, the increase in effect compared to the amount used is minimal, making it uneconomical.
- Foodologically acceptable salts may apply mutatis mutandis to pharmaceutically acceptable salts.
- Food compositions of the present invention include, for example, noodles, gums, dairy products, ice cream, meat, grains, caffeinated beverages, general beverages, chocolate, bread, snacks, confectionery, candy, pizza, jelly, alcoholic beverages, alcohol, and vitamin complexes. and other health supplements, but is not necessarily limited thereto.
- the food composition of the present invention when used as a food additive, it can be added as is or used together with other foods or food ingredients, and can be used appropriately according to conventional methods.
- the food composition includes health functional foods.
- health functional food refers to food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with Act No. 6727 on Health Functional Food, and “functionality” refers to the structure of the human body. It means ingestion for the purpose of controlling nutrients for function or obtaining useful effects for health purposes such as physiological effects.
- the food composition and health functional food of the present invention may contain additional ingredients.
- it may include biotin, folate, panthotenic acid, vitamins A, C, D, E, B1, B2, B6, B12, niacin, etc.
- minerals such as chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn), iron (Fe), and calcium (Ca).
- amino acids such as cysteine, valine, lysine, and tryptophan.
- preservatives potassium sorbate, sodium benzoate, salicylic acid, sodium dihydroacetate, etc.
- colorants tar color, etc.
- coloring agents sodium nitrite, sodium nitrite, etc.
- bleaching agents sodium sulfite
- disinfectants bleaching powder, high-level bleaching powder, Sodium hypochlorite, etc.
- swelling agents alum, D-potassium hydrogen tartrate, etc.
- strengthening agents emulsifiers, thickeners (greasing), coating agents, antioxidants (butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), etc.) , seasonings (MSG monosodium glutamate, etc.), sweeteners (dulcine, cyclamate, saccharin, sodium, etc.), flavorings (vanillin, lactones, etc.), food additives such as gum base agents, anti-foam agents, solvents, improvers, etc. can be added
- Talampanel of the present invention has excellent anti-depressant and anti-stress effects and can be usefully used to improve and treat stress- and depression-related diseases.
- Figure 1 is a diagram showing an outline of an experiment to verify the antidepressant effect of talampanel administration at different concentrations in a chronic movement-restricted stress-based depression mouse model over 15 days.
- Figure 2 is a diagram showing an outline of an experiment to verify the antidepressant effect of talampanel administration at different concentrations in a chronic movement-restricted stress-based depression mouse model over 28 days.
- Figure 3 is a diagram showing the amount of change in body weight of mice following administration of talampanel at each concentration along with movement restriction stress over 15 days.
- Figure 4 is a diagram analyzing the level of despair behavior of depression through a forced swimming test in mice following the administration of talampanel at different concentrations along with movement restriction stress over 15 days.
- Figure 5 is a diagram analyzing the level of despair behavior of depression through a forced swimming test in mice following movement restriction stress over 28 days and administration of talampanel at various concentrations.
- Figure 6 is a diagram analyzing the level of despair behavior of depression through a tail hanging test in mice following administration of talampanel at different concentrations along with movement restriction stress over 28 days.
- Figure 7 is a diagram analyzing the level of anhedonia in depression through a sugar preference test in mice following the administration of talampanel at different concentrations along with movement restriction stress over 28 days.
- Example 1 Evaluation of the efficacy of improving depression by administration of talampanel in a mouse model of depression induced by chronic movement restriction stress
- mice 8-9 week old male C57BL6/J mice were provided through Hyochang Science. Mice were provided with food and water to consume ad libitum under diurnal lighting conditions (12 hours light, 12 hours dark). All animal experiment procedures were approved by the Pohang University of Science and Technology Animal Experiment Ethics Committee (IACUC), and all experiments were performed in accordance with approved guidelines.
- IACUC Pohang University of Science and Technology Animal Experiment Ethics Committee
- talampanel showed an improvement effect on weight loss due to stress and depression by preventing weight loss due to continuous stress.
- a cylindrical tank measuring 20 cm in diameter x 30 cm in height was filled with water at 25-28°C until the height was 15 cm. Afterwards, each mouse was carefully placed in water, and its activity was recorded by video recording for 6 minutes. Up to four mice were conducted simultaneously at a time, and a partition was installed to prevent the mice from seeing each other. The water in the tank was freshly prepared after each test session.
- the movement of the mouse was defined as any movement other than the minimum required to maintain body balance and keep the head above water, and immobile time was measured.
- the forced swim test is an experiment in which water is placed in a cylindrical, obstacle-free container and the rat is placed in it, and the time taken to determine the movement of the rat is determined. It is a representative measure of depressive behavior. The longer the immobile time, the more depressed the individual is judged to be.
- mice's tail was fixed with tape, and the mouse's head was placed on the ceiling of a 25 cm wide x 25 cm long x 40 cm high white box with its head about 15 cm above the ground. The length was adjusted so that it fell apart, and the tail was attached.
- mice The activity of each mouse was recorded by video recording for 6 minutes. Up to four mice were treated at the same time, and the immobile time of the mice was measured for a total of 6 minutes. The movement of the mouse was defined as a state in which all limbs did not move based on whether the mouse had limb movement, and the immobile time was measured.
- the tail suspension test measures the time it takes for an animal to stop moving to escape by suspending the tail off the ground. As with FST, the longer the immobile time, the more depressed the individual is judged to be. Since the FST may be due to the immobility of the animal due to the impact of falling into the water, a TST test may be required for a more accurate test. In other words, the TST is characterized by being more sensitive to antidepressants than the FST because animals remain immobile for a longer period of time in the FST.
- mice were deprived of food and water for 18 hours on the first day of the experiment (food and water deprivation), and then provided with food on the second and third days. % sugar solution and water were provided simultaneously, providing experience with 2% sugar. Afterwards, on the 4th day, food and water were withheld for 18 hours, and then on the 5th day of the experiment, 2% sugar solution and water were provided simultaneously for 3 hours, allowing free choice. To measure the mouse's intake, the weight of the solution and bottle were recorded before and after the 3-hour test.
- the sugar preference test is a measure of anhedonia caused by depression. This was an experiment in which rats were given regular water and a 1% sugar solution to see which liquid they preferred. Normal rats tended to prefer the sugar solution, but depressed/anhedonic rats had a preference for the sugar solution. There was little difference in preference.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a composition for ameliorating, preventing, or treating stress and depression-related diseases, the composition containing talampanel. The talampanel in the present invention has excellent antidepressant and antistress efficacies and thus can be effectively used in the amelioration and treatment of diseases associated with stress and depression.
Description
본 발명은 탈람파넬을 포함하는 스트레스 및 우울증 관련 질환의 개선, 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition containing talampanel for improving, preventing or treating diseases related to stress and depression.
현대사회는 급증하는 스트레스 등으로 인한 불안, 우울, 정신분열 등을 포함하는 뇌신경정신질환이 증가하고 있다. 특히 개인주의가 팽배한 현 시대의 사회적, 구조적 원인 등의 다양한 원인으로 스트레스 및 우울증을 겪는 환자들이 증가하는 추세이다.In modern society, neuropsychiatric diseases including anxiety, depression, and schizophrenia are on the rise due to rapidly increasing stress. In particular, in the current era where individualism is prevalent, the number of patients suffering from stress and depression is increasing due to various causes, including social and structural causes.
스트레스 및 우울증을 겪는 환자들은 심할 경우 자살로 이어질 수 있고, 특히 우울증 환자의 과반수 이상이 자살을 고려하는 것으로 보고된 바 있으며, 실제로 우울증을 경험한 환자의 10 내지 15%가 자살을 시행하는 것으로 알려졌다.Patients suffering from stress and depression can, in severe cases, lead to suicide. In particular, it has been reported that more than half of patients with depression consider suicide, and in fact, 10 to 15% of patients who experience depression are known to commit suicide. .
하지만, 사회적 경각심이 필요한 이러한 질병이 부정적인 사회 인식으로 인해 질병의 진단은 물론 치료 자체도 제대로 이루어지지 않는 실정이며, 항우울제 등의 약물들은 대게 치료 효과가 크지 않다는 것이 가장 큰 문제로 남아있다.However, due to the negative social perception of these diseases that require social awareness, not only the diagnosis but also the treatment of the disease itself is not carried out properly, and the biggest problem remains that drugs such as antidepressants usually do not have a significant treatment effect.
한편, 탈람파넬(Talampanel)은 중추신경계에 있는 이오노트로픽 글루탐산 수용체(ionotropic glutamate receptor)의 일종인 AMPA(alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) 수용체의 비경쟁적 길항제 역할을 하며, 간질, 악성 신경교종, 외상성 뇌손상, 뇌전증 및 근위축성 측삭경화증(amyotrophic lateral sclerosis, ALS)의 치료를 위해 연구된 약물이다.Meanwhile, Talampanel acts as a non-competitive antagonist of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, a type of ionotropic glutamate receptor in the central nervous system. It is a drug studied for the treatment of epilepsy, malignant glioma, traumatic brain injury, epilepsy, and amyotrophic lateral sclerosis (ALS).
본 발명자들은 스트레스 유도 우울증 모델에서 탈람파넬의 스트레스 및 우울증에 관한 개선 및 치료 효능을 확인함에 따라 탈람파넬의 스트레스 및 우울증에 관한 개선 및 치료에 유용하게 사용할 수 있음을 확인하고 본 발명을 완성하였다.The present inventors confirmed that talampanel can be effectively used to improve and treat stress and depression by confirming the efficacy of talampanel in improving and treating stress and depression in a stress-induced depression model, and completed the present invention.
본 발명의 목적은 하기 화학식 1로 표시되는 탈람파넬(talampanel) 또는 이의 약학적으로 허용가능한 염을 포함하는 스트레스 및 우울증 관련 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.The purpose of the present invention is to provide a pharmaceutical composition for preventing or treating diseases related to stress and depression, comprising talampanel or a pharmaceutically acceptable salt thereof represented by the following formula (1).
[화학식 1][Formula 1]
본 발명의 목적은 탈람파넬(talampanel)의 스트레스 및 우울증 관련 질환 치료 용도를 제공하는 것이다. The purpose of the present invention is to provide the use of talampanel in the treatment of diseases related to stress and depression.
본 발명의 목적은 탈람파넬(talampanel)을 이를 필요로 하는 개체에게 투여하는 스트레스 및 우울증 관련 질환 치료 방법을 제공하는 것이다. The purpose of the present invention is to provide a method of treating stress and depression-related diseases by administering talampanel to an individual in need thereof.
본 발명은 하기 화학식 1로 표시되는 탈람파넬(talampanel) 또는 이의 약학적으로 허용가능한 염을 포함하는 스트레스 및 우울증 관련 질환 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating diseases related to stress and depression, comprising talampanel or a pharmaceutically acceptable salt thereof represented by the following formula (1).
[화학식 1][Formula 1]
본 발명에 따르면, 상기 탈람파넬(talampanel)은 위 화학식 1의 구조를 가진다. According to the present invention, the talampanel has the structure of Formula 1 above.
이러한, 탈람파넬(talampanel)은 스트레스 및 우울증 관련 질환에 대하여 우수한 개선 효과를 나타낸다. Talampanel shows excellent improvement effects on stress and depression-related diseases.
위 언급된 스트레스 및 우울증 관련 질환은, 의욕 상실과 지속되는 우울감으로 인해 인지 및 정신적, 신체적 증상이 나타나 일상 기능이 저하되는 증상을 포함하는 개념이다. 지속적인 우울감, 의욕 저하, 불면증 등의 수면장애, 식욕저하 또는 식욕 증가와 관련한 체중 변화, 자살에 대한 반복적인 생각이나 시도, 부정적 사고, 지나친 죄책감 등을 포함하여, 상기 증상과 관련된 스트레스 및 우울증 관련 질환을 의미한다. The stress- and depression-related diseases mentioned above are a concept that includes symptoms in which cognitive, mental, and physical symptoms appear due to loss of motivation and persistent depression, leading to a decline in daily functioning. Stress and depression-related diseases related to the above symptoms, including persistent depression, decreased motivation, sleep disorders such as insomnia, weight changes related to decreased or increased appetite, repeated thoughts or attempts of suicide, negative thinking, excessive guilt, etc. means.
일 예로 우울증, 스트레스, 수술 후 스트레스 증후군, 스트레스에 의한 군발성 두통, 스트레스에 의한 편두통, 스트레스에 의한 원인불명의 통증, 스트레스로 인한 불면증, 기억 장애, 인지 장애 및 주의력 장애로 이루어진 군으로부터 선택되는 어느 하나일 수 있다.For example, depression, stress, post-operative stress syndrome, cluster headache due to stress, migraine due to stress, unexplained pain due to stress, insomnia due to stress, memory disorder, cognitive disorder, and attention disorder. It could be any one.
본 발명의 일실시양태에 따르면, 탈람파넬은 스트레스 유도 우울증 동물모델을 대상으로 한 실험에서 우수한 항우울 및 항스트레스 효능을 보유함에 따라, 탈람파넬은 스트레스 및 우울증 관련 질환의 개선 및 치료에 유용하게 이용될 수 있음을 확인하였다. According to one embodiment of the present invention, talampanel has excellent antidepressant and anti-stress efficacy in experiments conducted on animal models of stress-induced depression, and thus talampanel is useful for improving and treating diseases related to stress and depression. It was confirmed that it can be used.
특히, 지속적 혹은 반복적인 스트레스의 축적을 억제함으로써 질환 치료에 우수한 효능을 나타낼 수 있다. In particular, it can show excellent efficacy in treating diseases by suppressing the accumulation of continuous or repetitive stress.
본 발명에서 사용되는 용어 “예방”은 조성물의 투여로 스트레스 및 우울증 관련 질환을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다. 본 발명에 있어서, “치료”란 조성물의 투여로 상기 질환의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.The term “prevention” used in the present invention refers to all actions that suppress or delay the onset of diseases related to stress and depression by administering a composition. In the present invention, “treatment” means any action in which the symptoms of the disease are improved or beneficially changed by administration of the composition.
본 발명에서, 약학적으로 허용가능한 염은 의약업계에서 통상적으로 사용되는 염을 의미하며, 예를 들어 칼슘, 포타슘, 소듐 및 마그네슘 등으로 제조된 무기이온염; 염산, 질산, 인산, 브롬산, 요오드산, 과염소산 및 황산 등으로 제조된 무기산염; 아세트산, 트라이플루오로아세트산, 시트르산, 말레인산, 숙신산, 옥살산, 벤조산, 타르타르산, 푸마르산, 만데르산, 프로피온산, 젖산, 글리콜산, 글루콘산, 갈락투론산, 글루탐산, 글루타르산, 글루쿠론산, 아스파르트산, 아스코르브산, 카본산, 바닐릭산, 하이드로 아이오딕산 등으로 제조된 유기산염; 메탄설폰산, 에탄설폰산, 벤젠설폰산, p-톨루엔설폰산 및 나프탈렌설폰산 등으로 제조된 설폰산염; 글리신, 아르기닌, 라이신 등으로 제조된 아미노산염; 및 트리메틸아민, 트라이에틸아민, 암모니아, 피리딘, 피콜린 등으로 제조된 아민염 등이 있으나, 열거된 이들 염에 의해 본 발명에서 의미하는 염의 종류가 한정되는 것은 아니다.In the present invention, pharmaceutically acceptable salts refer to salts commonly used in the pharmaceutical industry, such as inorganic ionic salts made of calcium, potassium, sodium, magnesium, etc.; Inorganic acid salts made from hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, iodic acid, perchloric acid and sulfuric acid; Acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid. Organic acid salts made from acids, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc.; Sulfonic acid salts made from methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, etc.; Amino acid salts made from glycine, arginine, lysine, etc.; and amine salts prepared from trimethylamine, triethylamine, ammonia, pyridine, picoline, etc., but the types of salts meant in the present invention are not limited by these salts listed.
또한, 본 발명의 상기 화학식 1로 표시되는 탈람파넬은 약학적으로 허용되는 염뿐만 아니라, 통상의 방법에 의해 제조될 수 있는 모든 염, 수화물 및 용매화물을 모두 포함한다.In addition, talampanel represented by Formula 1 of the present invention includes not only pharmaceutically acceptable salts, but also all salts, hydrates, and solvates that can be prepared by conventional methods.
본 발명의 약학 조성물은 약학적으로 허용가능한 담체를 포함할 수 있으며, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제제화될 수 있다.The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier, and may be prepared in oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, etc. according to conventional methods. It may be formulated in the form of a sterile injectable solution.
상기 약제학적으로 허용가능한 담체는 당업계에서 통상적으로 사용되는 것들, 예컨대 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함하나 이에 국한되지 않는다. 또한, 본 발명의 약학 조성물은 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제, 기타 약제학적으로 허용가능한 첨가제를 포함할 수 있으나, 이에 국한되지 않는다.The pharmaceutically acceptable carriers include those commonly used in the art, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, Including, but not limited to, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition, the pharmaceutical composition of the present invention may contain diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and other pharmaceutically acceptable additives, but is not limited thereto.
본 발명의 약학 조성물이 경구용 고형 제제로 제제화된 경우 정제, 환제, 산제, 과립제, 캡슐제 등을 포함하며, 이러한 고형제제는 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토즈, 젤라틴 등을 포함할 수 있으며, 마그네슘 스테아레이트, 탈크 같은 윤활제 등을 포함하나 이에 국한되지 않는다. When the pharmaceutical composition of the present invention is formulated as an oral solid preparation, it includes tablets, pills, powders, granules, capsules, etc., and such solid preparations contain at least one excipient, such as starch, calcium carbonate, It may contain sucrose or lactose, gelatin, etc., and includes, but is not limited to, lubricants such as magnesium stearate and talc.
본 발명의 약학 조성물이 경구용 액상 제제화된 경우 현탁제, 내용액제, 유제, 시럽제 등을 포함하며, 물, 리퀴드 파라핀 등의 희석제, 습윤제, 감미제, 방향제, 보존제 등을 포함하나 이에 국한되지 않는다. When the pharmaceutical composition of the present invention is formulated in liquid form for oral use, it includes suspensions, oral solutions, emulsions, syrups, etc., and includes, but is not limited to, diluents such as water and liquid paraffin, humectants, sweeteners, fragrances, preservatives, etc.
본 발명의 약학 조성물이 비경구용 제제화된 경우 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제를 포함하며, 비수성 용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르류 등을 포함하나 이에 국한되지 않는다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있으나 이에 국한되지 않는다.When the pharmaceutical composition of the present invention is formulated for parenteral use, it includes sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, and olive. Includes, but is not limited to, vegetable oils such as oil, injectable esters such as ethyl oleate, etc. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurel, glycerogelatin, etc. can be used, but are not limited to these.
상기 조성물은 약학적으로 유효한 양으로 단일 또는 다중 투여될 수 있다. 본 발명의 용어 "약학적으로 유효한 양"이란 의학적 예방 또는 치료에 적용가능한 합리적인 수혜/위험 비율로 질환을 예방 또는 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 질환의 중증도, 약물의 활성, 환자의 연령, 체중, 건강, 성별, 환자의 약물에 대한 민감도, 사용된 본 발명 조성물의 투여 시간, 투여 경로 및 배출 비율, 치료기간, 사용된 본 발명의 조성물과 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 예를 들면, 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염은 1일 0.0001 내지 100 mg/kg으로 투여할 수 있으며, 상기 투여는 하루에 한 번 또는 수회 나누어 투여할 수도 있다.The composition can be administered singly or multiple times in a pharmaceutically effective amount. The term "pharmaceutically effective amount" of the present invention means an amount sufficient to prevent or treat a disease with a reasonable benefit/risk ratio applicable to medical prevention or treatment, and the effective dose level is determined by the severity of the disease, the activity of the drug, Including the patient's age, weight, health, gender, patient's sensitivity to drugs, administration time, administration route and excretion rate of the composition of the present invention used, treatment period, and drugs mixed or used simultaneously with the composition of the present invention used. It can be determined according to factors well known in the medical field and other factors. For example, the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof can be administered at 0.0001 to 100 mg/kg per day, and the administration may be administered once a day or in divided doses.
본 발명의 약학 조성물은 랫트, 마우스, 가축, 인간 등의 포유동물에 다양한 경로로, 예를 들면, 경구 투여, 경막내, 내이, 복강 또는 정맥, 근육, 피하, 자궁 내 경막, 설하 또는 뇌혈관 내 주사에 의해 투여될 수 있으며, 이에 국한되지 않는다.The pharmaceutical composition of the present invention is administered to mammals such as rats, mice, livestock, and humans by various routes, for example, by oral administration, intrathecium, inner ear, abdominal cavity or vein, muscle, subcutaneous, intrauterine dura, sublingual or cerebrovascular administration. It may be administered by injection, but is not limited to this.
본 발명의 약학 조성물은 조성물 총 중량에 대하여 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염을 0.01 내지 95 중량%, 바람직하게는 1 내지 80 중량%로 포함할 수 있다.The pharmaceutical composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight, of the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof, based on the total weight of the composition.
본 발명의 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와 순차적으로 또는 동시에 투여될 수 있다. 또한 본 발명의 약학적 조성물은 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. Additionally, the pharmaceutical composition of the present invention can be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art.
본 발명의 용어 "개체"는 본 발명에 따른 약학적 조성물의 투여에 의해 증상이 호전될 수 있는 동물 또는 인간을 포함한다. 본 발명에 따른 치료용 조성물을 개체에게 투여함으로써, 스트레스 및 우울증 관련 질환을 효과적으로 예방 및 치료할 수 있다.The term “subject” of the present invention includes animals or humans whose symptoms can be improved by administration of the pharmaceutical composition according to the present invention. By administering the therapeutic composition according to the present invention to an individual, diseases related to stress and depression can be effectively prevented and treated.
본 발명의 용어 "투여"는 어떠한 적절한 방법으로 인간 또는 동물에게 소정의 물질을 도입하는 것을 의미하며, 본 발명에 따른 치료용 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 본 발명에 따른 치료용 조성물은 유효성분이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다. The term "administration" of the present invention means introducing a predetermined substance into a human or animal by any appropriate method, and the route of administration of the therapeutic composition according to the present invention is through any general route as long as it can reach the target tissue. It may be administered orally or parenterally. Additionally, the therapeutic composition according to the present invention can be administered by any device that can move the active ingredient to target cells.
본 발명의 다른 하나의 양태는 치료학적으로 유효한 양의 상기 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용 가능한 염을 이를 필요로 하는 개체에게 투여하는 단계를 포함하는 스트레스 및 우울증 관련 질환의 예방 또는 치료 방법을 제공한다.Another aspect of the present invention is the prevention of stress and depression-related diseases, comprising administering a therapeutically effective amount of the compound represented by Formula 1, or a pharmaceutically acceptable salt thereof, to an individual in need thereof. Or provide a treatment method.
본 발명에서 용어 "화학식 1로 표시되는 화합물" 또는 "스트레스 및 우울증 관련 질환"은 전술한 바와 같다.In the present invention, the term “compound represented by Formula 1” or “stress and depression-related disease” is as described above.
본 발명의 용어 "개체"란 스트레스 및 우울증 관련 질환이 발병하였거나 발병할 수 있는 모든 동물을 의미하며, 전형적으로 본 발명의 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용 가능한 염을 이용한 치료로 유익한 효과를 나타낼 수 있는 동물일 수 있으나, 스트레스 및 우울증 관련 질환의 증상을 갖거나 이러한 증상을 가질 가능성이 있는 개체이면 제한없이 포함한다. 전술한 바와 같이, 본 발명의 약학 조성물을 개체에게 투여함으로써 상기 스트레스 및 우울증 관련 질환을 효과적으로 예방 또는 치료할 수 있다. The term "individual" of the present invention refers to any animal that has developed or can develop diseases related to stress and depression, and is typically treated with a compound represented by Formula 1 of the present invention, or a pharmaceutically acceptable salt thereof. It may be an animal that can show beneficial effects, but any animal that has symptoms of stress or depression-related diseases or is likely to have these symptoms is included without limitation. As described above, the stress- and depression-related diseases can be effectively prevented or treated by administering the pharmaceutical composition of the present invention to an individual.
본 발명의 다른 하나의 양태는 스트레스 및 우울증 관련 질환의 예방 또는 치료를 위한 의약을 제조하기 위한 본 발명의 상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염의 용도를 제공한다.Another aspect of the present invention provides the use of the compound represented by Formula 1 of the present invention, or a pharmaceutically acceptable salt thereof, for manufacturing a medicine for preventing or treating diseases related to stress and depression.
본 발명의 다른 또 하나의 양태는 스트레스 및 우울증 관련 질환의 예방 또는 치료에 사용하기 위한 상기 화학식 1로 표시되는 화합물 또는 이의 약학적으로 허용 가능한 염을 포함하는 약학 조성물을 제공한다.Another aspect of the present invention provides a pharmaceutical composition comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of diseases related to stress and depression.
본 발명은 하기 화학식 1로 표시되는 탈람파넬(talampanel) 또는 이의 식품학적으로 허용가능한 염을 포함하는 스트레스 및 우울증 관련 질환 예방 또는 개선용 식품 조성물을 제공한다.The present invention provides a food composition for preventing or improving diseases related to stress and depression, comprising talampanel or a foodologically acceptable salt thereof represented by the following formula (1).
[화학식 1][Formula 1]
본 발명의 용어, "개선"이란, 본 발명의 조성물의 투여로 스트레스 및 우울증 관련 질환이 호전 또는 이롭게 변경되는 모든 행위를 의미한다.The term "improvement" in the present invention refers to any action in which stress- and depression-related diseases are improved or beneficially changed by administration of the composition of the present invention.
본 발명의 식품 조성물에 있어, 상기 탈람파넬 및 그의 염은 바람직하게 식품 조성물 대비 0.00001~0.01 중량% 포함되는 것이 좋다. 0.00001 중량% 미만일 경우에는 그 효과가 미비하고, 0.01 중량%를 초과하는 경우에는 사용량 대비 효과 증가가 미미하여 비경제적이다.In the food composition of the present invention, the talampanel and its salt are preferably contained in an amount of 0.00001 to 0.01% by weight relative to the food composition. If it is less than 0.00001% by weight, the effect is insignificant, and if it exceeds 0.01% by weight, the increase in effect compared to the amount used is minimal, making it uneconomical.
식품학적으로 허용가능한 염은 약학적으로 허용가능한 염의 내용을 준용할 수 있다. Foodologically acceptable salts may apply mutatis mutandis to pharmaceutically acceptable salts.
본 발명의 식품 조성물은 일 예로, 면류, 껌류, 유제품류, 아이스크림류, 육류, 곡류, 카페인 음료, 일반음료, 초콜릿, 빵류, 스낵류, 과자류, 사탕, 피자, 젤리, 알코올성 음료, 술, 비타민 복합제 및 그 밖의 건강보조식품류 중 선택되는 어느 하나일 수 있으나, 반드시 이에 한정되는 것은 아니다.Food compositions of the present invention include, for example, noodles, gums, dairy products, ice cream, meat, grains, caffeinated beverages, general beverages, chocolate, bread, snacks, confectionery, candy, pizza, jelly, alcoholic beverages, alcohol, and vitamin complexes. and other health supplements, but is not necessarily limited thereto.
본 발명의 식품 조성물을 식품 첨가물로 사용할 경우, 이를 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다.When the food composition of the present invention is used as a food additive, it can be added as is or used together with other foods or food ingredients, and can be used appropriately according to conventional methods.
본 발명에서 식품 조성물은 건강기능식품을 포함한다.In the present invention, the food composition includes health functional foods.
상기 "건강기능식품"이라 함은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.The above “health functional food” refers to food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with Act No. 6727 on Health Functional Food, and “functionality” refers to the structure of the human body. It means ingestion for the purpose of controlling nutrients for function or obtaining useful effects for health purposes such as physiological effects.
본 발명의 식품 조성물 및 건강기능식품은 추가 성분을 포함할 수 있다. 예들 들어, 비오틴(biotin), 폴레이트(folate), 판토텐산(panthotenic acid), 비타민 A, C, D, E, B1, B2, B6, B12, 니아신(niacin) 등을 포함할 수 있다. 또한, 크롬(Cr), 마그네슘(Mg), 망간(Mn), 구리(Cu), 아연(Zn), 철(Fe), 칼슘(Ca) 등의 미네랄을 포함할 수 있다. 또한, 시스테인, 발린, 라이신, 트립토판 등의 아미노산을 포함할 수 있다. 또한, 방부제(소르빈산 칼륨, 벤조산나트륨, 살리실산, 디히드로초산나트륨 등), 착색제(타르색소 등), 발색제(아질산 나트륨, 아초산 나트륨 등), 표백제(아황산나트륨), 살균제(표백분과 고도 표백분, 차아염소산나트륨 등), 팽창제(명반, D-주석산수소칼륨 등), 강화제, 유화제, 증점제(호료), 피막제, 산화방지제(부틸히드록시아니졸(BHA), 부틸히드록시톨루엔(BHT) 등), 조미료(MSG 글루타민산나트륨 등), 감미료(둘신, 사이클레메이트, 사카린, 나트륨 등), 향료(바닐린, 락톤류 등), 검기초제, 거품억제제, 용제, 개량제 등의 식품 첨가물(food additives)을 첨가할 수 있다. 상기 첨가물은 식품의 종류에 따라 선별되고 적절한 양으로 사용될 수 있다.The food composition and health functional food of the present invention may contain additional ingredients. For example, it may include biotin, folate, panthotenic acid, vitamins A, C, D, E, B1, B2, B6, B12, niacin, etc. Additionally, it may contain minerals such as chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn), iron (Fe), and calcium (Ca). Additionally, it may contain amino acids such as cysteine, valine, lysine, and tryptophan. In addition, preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dihydroacetate, etc.), colorants (tar color, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), disinfectants (bleaching powder, high-level bleaching powder, Sodium hypochlorite, etc.), swelling agents (alum, D-potassium hydrogen tartrate, etc.), strengthening agents, emulsifiers, thickeners (greasing), coating agents, antioxidants (butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), etc.) , seasonings (MSG monosodium glutamate, etc.), sweeteners (dulcine, cyclamate, saccharin, sodium, etc.), flavorings (vanillin, lactones, etc.), food additives such as gum base agents, anti-foam agents, solvents, improvers, etc. can be added. The additives can be selected depending on the type of food and used in an appropriate amount.
본 발명의 탈람파넬은 우수한 항우울 및 항스트레스 효능을 보유함에 따라, 스트레스 및 우울증 관련 질환의 개선 및 치료에 유용하게 이용될 수 있다.Talampanel of the present invention has excellent anti-depressant and anti-stress effects and can be usefully used to improve and treat stress- and depression-related diseases.
도 1은 15일에 걸친 만성 움직임 제한 스트레스 기반 우울증 마우스 모델을 대상으로 농도별 탈람파넬 투여에 따른 항우울 효과를 검증하기 위한 실험 개요를 나타낸 도이다.Figure 1 is a diagram showing an outline of an experiment to verify the antidepressant effect of talampanel administration at different concentrations in a chronic movement-restricted stress-based depression mouse model over 15 days.
도 2는 28일에 걸친 만성 움직임 제한 스트레스 기반 우울증 마우스 모델을 대상으로 농도별 탈람파넬 투여에 따른 항우울 효과를 검증하기 위한 실험 개요를 나타낸 도이다.Figure 2 is a diagram showing an outline of an experiment to verify the antidepressant effect of talampanel administration at different concentrations in a chronic movement-restricted stress-based depression mouse model over 28 days.
도 3은 15일에 걸친 움직임 제한 스트레스와 함께 농도별 탈람파넬 투여에 따른 마우스의 체중 변화량을 나타낸 도이다.Figure 3 is a diagram showing the amount of change in body weight of mice following administration of talampanel at each concentration along with movement restriction stress over 15 days.
도 4는 15일에 걸친 움직임 제한 스트레스와 함께 농도별 탈람파넬 투여에 따른 마우스의 강제 수영 시험을 통한 우울증의 절망행동 (despair behavior) 수준을 분석한 도이다.Figure 4 is a diagram analyzing the level of despair behavior of depression through a forced swimming test in mice following the administration of talampanel at different concentrations along with movement restriction stress over 15 days.
도 5는 28일에 걸친 움직임 제한 스트레스와 함께 농도별 탈람파넬 투여에 따른 마우스의 강제 수영 시험을 통한 우울증의 절망행동 (despair behavior) 수준을 분석한 도이다.Figure 5 is a diagram analyzing the level of despair behavior of depression through a forced swimming test in mice following movement restriction stress over 28 days and administration of talampanel at various concentrations.
도 6은 28일에 걸친 움직임 제한 스트레스와 함께 농도별 탈람파넬 투여에 따른 마우스의 꼬리 매달기 시험을 통한 우울증의 절망행동 (despair behavior) 수준을 분석한 도이다.Figure 6 is a diagram analyzing the level of despair behavior of depression through a tail hanging test in mice following administration of talampanel at different concentrations along with movement restriction stress over 28 days.
도 7은 28일에 걸친 움직임 제한 스트레스와 함께 농도별 탈람파넬 투여에 따른 마우스의 설탕 선호 시험을 통한 우울증의 무쾌감증(anhedonia) 수준을 분석한 도이다.Figure 7 is a diagram analyzing the level of anhedonia in depression through a sugar preference test in mice following the administration of talampanel at different concentrations along with movement restriction stress over 28 days.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하 여 제공되는 것일 뿐, 이에 의해 본 발명의 내용이 한정되는 것은 아니다.Below, preferred embodiments are presented to aid understanding of the present invention. However, the following examples are provided only to make the present invention easier to understand, and the content of the present invention is not limited thereto.
[실시예 1: 만성 움직임 제한 스트레스를 유도한 우울증 마우스 모델에서의 탈람파넬 투여에 따른 우울증 개선 효능 평가][Example 1: Evaluation of the efficacy of improving depression by administration of talampanel in a mouse model of depression induced by chronic movement restriction stress]
1. 만성 움직임 제한 스트레스 (Chronic restraint stress) 기반 우울증 모델 유도1. Derivation of depression model based on chronic restraint stress
8~9주령 수컷 C57BL6/J 마우스를 효창사이언스를 통해 제공받았다. 마우스는 주행성 조명 조건(12시간 빛(light), 12시간 암(dark)) 하에서 자유롭게 (ad libitum) 섭취할 수 있도록 음식과 물을 제공하였다. 모든 동물 실험 절차는 포항공과대학교 동물실험윤리위원회 (IACUC)의 승인을 받았으며, 모든 실험은 승인된 지침에 따라 수행하였다.8-9 week old male C57BL6/J mice were provided through Hyochang Science. Mice were provided with food and water to consume ad libitum under diurnal lighting conditions (12 hours light, 12 hours dark). All animal experiment procedures were approved by the Pohang University of Science and Technology Animal Experiment Ethics Committee (IACUC), and all experiments were performed in accordance with approved guidelines.
만성 움직임 제한 스트레스 기반 우울증 모델의 유도를 위하여 8~9주령 수컷 C57BL6/J 마우스를 실험 하루 전 단독 케이지(single cage)에서 하우징(housing)을 시작하였다.To induce a chronic movement restriction stress-based depression model, 8-9 week old male C57BL6/J mice were housed in a single cage one day before the experiment.
도 1 및 2에 나타낸 바와 같이, 15일 및 28일간 매일 오전 10시에서 오후 12시 사이에 마우스 무게를 측정한 후, 대조군은 0.9%(w/v)의 염분이 함유된 10%(v/v) DMSO를, 실험군은 탈람파넬 용액 (final concentration 0.1 or 1.0 ㎎/㎖ in vehicle)을 마우스 무게 1g당 10㎕씩 복강내 주사 (intraperitoneal, i.p.) 방식으로 주입하였다. 약물 투여 30분 후 마우스를 호흡이 가능하도록 구멍을 낸 50㎖ 코니칼 튜브(conical tube)에 들어가도록 유도하고 종이타월을 넣어 빈 공간이 없게 하여 움직임 제한(restraint) 상태를 4시간 동안 유지하였다.As shown in Figures 1 and 2, after weighing the mice daily between 10 AM and 12 PM for 15 and 28 days, the control group was exposed to 10% (v/v) saline containing 0.9% (w/v) saline. v) DMSO and talampanel solution (final concentration 0.1 or 1.0 ㎎/㎖ in vehicle) were injected intraperitoneally (i.p.) at 10㎕ per 1g of mouse weight in the experimental group. 30 minutes after drug administration, the mouse was induced to enter a 50 ㎖ conical tube with a hole to allow breathing, and a paper towel was placed to leave no empty space, and the mouse was kept in a state of restricted movement for 4 hours.
2. 체중 변화량 측정2. Measurement of weight change
만성 스트레스 유도 우울증 마우스 모델의 체중 변화량을 측정하기 위하여, 15일 및 28일간 매일 오전 10시에서 오후 12시 사이에 마우스 무게를 측정한 결과, 도 3에 나타낸 바와 같이 15일간에 걸친 실험 수행군에서 탈람파넬 1㎎/㎏ 및 10㎎/㎏ 투여군 모두에서 투여 8일째부터 대조군 대비 몸무게가 증가하는 것을 확인할 수 있었다.In order to measure the amount of change in body weight in the chronic stress-induced depression mouse model, the weight of the mouse was measured every day between 10:00 AM and 12:00 PM for 15 and 28 days. As shown in Figure 3, in the group that performed the experiment for 15 days, It was confirmed that body weight increased compared to the control group from the 8th day of administration in both the 1 mg/kg and 10 mg/kg talampanel groups.
탈람파넬의 투여는 지속적 스트레스에 따른 체중감소를 방지함으로써 스트레스 및 우울증으로 인한 체중 감소에 대해 개선 효과를 나타냄을 확인하였다. It was confirmed that the administration of talampanel showed an improvement effect on weight loss due to stress and depression by preventing weight loss due to continuous stress.
3. 강제 수영 시험 (Forced swim test)3. Forced swim test
만성 스트레스 유도 우울증 마우스 모델의 강제 수영 시험을 수행하기 위하여, 지름 20㎝ x 높이 30㎝의 원통형 수조에 25~28℃의 물을 높이 15㎝가 될 때까지 채웠다. 이후, 각 마우스를 물에 조심스럽게 넣고 비디오 녹화로 6분 동안 마우스의 활동을 기록하였다. 한 번에 네 마리까지 동시에 진행하였으며 마우스가 서로 보지 못하도록 칸막이를 설치하였다. 수조의 물은 각 테스트 세션 후에 새로 준비하였다.To perform a forced swimming test in a mouse model of chronic stress-induced depression, a cylindrical tank measuring 20 cm in diameter x 30 cm in height was filled with water at 25-28°C until the height was 15 cm. Afterwards, each mouse was carefully placed in water, and its activity was recorded by video recording for 6 minutes. Up to four mice were conducted simultaneously at a time, and a partition was installed to prevent the mice from seeing each other. The water in the tank was freshly prepared after each test session.
총 6분의 녹화 중에 처음 2분은 습관작용(habituation)으로 제외하고, 이후 4분 동안 각 마우스가 움직이지 않은 시간(immobile time)을 측정하였다. 마우스의 움직임 여부는 몸의 균형을 유지하고 머리를 물 위로 유지하는데 필요한 최소한의 움직임 외의 모든 움직임으로 정의하고 움직이지 않은 시간(immobile time)을 측정하였다.Of the total 6 minutes of recording, the first 2 minutes were excluded due to habituation, and the immobile time of each mouse was measured for the next 4 minutes. The movement of the mouse was defined as any movement other than the minimum required to maintain body balance and keep the head above water, and immobile time was measured.
강제 수영 시험 (Forced swim test, FST)은 원통형의 장애물이 없는 통에 물을 담고 쥐를 빠뜨려서 쥐가 움직이는 시간을 판단하는 실험으로, 대표적인 우울 행동의 판단 척도가 된다. 움직이지 않은 시간(immobile time)이 길수록 해당 개체는 우울감을 느끼는 것으로 판단한다.The forced swim test (FST) is an experiment in which water is placed in a cylindrical, obstacle-free container and the rat is placed in it, and the time taken to determine the movement of the rat is determined. It is a representative measure of depressive behavior. The longer the immobile time, the more depressed the individual is judged to be.
실험 결과, 도 4 및 5에 나타낸 바와 같이 탈람파넬을 투여한 군은 대조군에 비하여 움직이지 않은 시간(immobile time)이 확연히 줄어든 것을 확인할 수 있었다.As a result of the experiment, as shown in Figures 4 and 5, it was confirmed that the immobile time in the group administered talampanel was significantly reduced compared to the control group.
4. 꼬리 매달기 시험 (Tail suspension test)4. Tail suspension test
만성 스트레스 유도 우울증 마우스 모델의 꼬리 매달기 시험을 수행하기 위하여, 마우스 꼬리를 테이프로 고정한 뒤, 가로 25㎝ x 세로 25㎝ x 높이 40㎝의 흰색 상자의 천장에 마우스의 머리가 지면에서 15㎝ 정도 떨어지도록 길이를 조정하여 꼬리를 부착하였다.To perform a tail suspension test in a mouse model of chronic stress-induced depression, the mouse's tail was fixed with tape, and the mouse's head was placed on the ceiling of a 25 cm wide x 25 cm long x 40 cm high white box with its head about 15 cm above the ground. The length was adjusted so that it fell apart, and the tail was attached.
각 마우스의 활동은 비디오 녹화로 6분 동안 기록하였다. 한번에 네 마리까지 동시에 진행하였고, 총 6분 동안 마우스가 움직이지 않은 시간(immobile time)을 측정하였다. 마우스의 움직임 여부는 마우스의 사지 움직임(limb movement) 여부를 기준으로 사지가 모두 움직이지 않는 상태를 정의하고 움직이지 않은 시간(immobile time)을 측정하였다.The activity of each mouse was recorded by video recording for 6 minutes. Up to four mice were treated at the same time, and the immobile time of the mice was measured for a total of 6 minutes. The movement of the mouse was defined as a state in which all limbs did not move based on whether the mouse had limb movement, and the immobile time was measured.
꼬리 매달기 시험 (Tail suspension test, TST)은 지면에서 떨어진 곳에 꼬리를 매달아 놓음으로써, 탈출을 위한 움직임이 멈추는 시간을 측정한다. FST와 동일하게 움직이지 않은 시간(immobile time)이 길수록 해당 개체는 우울감을 느끼는 것으로 판단한다. FST는 동물의 부동성이 물에 떨어지는 충격에 의한 것일 수 있으므로, 더욱 정확한 검사를 위해서는 TST 시험을 요하기도 한다. 즉, TST는 동물이 FST에서 더 오래 움직이지 않기 때문에 FST보다 항우울제에 더 민감한 것이 특징이다.The tail suspension test (TST) measures the time it takes for an animal to stop moving to escape by suspending the tail off the ground. As with FST, the longer the immobile time, the more depressed the individual is judged to be. Since the FST may be due to the immobility of the animal due to the impact of falling into the water, a TST test may be required for a more accurate test. In other words, the TST is characterized by being more sensitive to antidepressants than the FST because animals remain immobile for a longer period of time in the FST.
실험 결과, 도 6에 나타낸 바와 같이 탈람파넬을 투여한 군은 대조군에 비하여 움직이지 않은 시간(immobile time)이 확연히 줄어든 것을 확인할 수 있었다.As a result of the experiment, as shown in Figure 6, it was confirmed that the immobile time in the group administered talampanel was significantly reduced compared to the control group.
이에 따라, 탈람파넬의 투여는 강제 수영 시험에서와 동일하게 우수한 항우울 효능을 나타내는 것을 확인하였다. Accordingly, it was confirmed that administration of talampanel showed the same excellent antidepressant efficacy as in the forced swimming test.
5. 설탕 선호 시험 (Sucrose preference test)5. Sucrose preference test
만성 스트레스 유도 우울증 마우스 모델의 설탕 선호 시험을 수행하기 위하여, 실험 1일차에 마우스에게 18시간 동안 음식과 물을 공급하지 않은 뒤 (food, water deprivation), 2일차와 3일차에 음식을 제공하고 2% 설탕 용액과 물을 동시에 제공하여, 2% 설탕에 대한 경험을 제공하였다. 이후, 4일차에 18시간 동안 음식과 물을 공급하지 않은 뒤, 실험 5일차에 3시간 동안 2% 설탕 용액과 물을 동시에 제공하여 자유롭게 선택할 수 있도록 하였다. 마우스의 섭취량을 측정하기 위해 3시간에 걸친 테스트 전후 용액과 병의 무게를 기록하였다.To perform a sugar preference test in a mouse model of chronic stress-induced depression, mice were deprived of food and water for 18 hours on the first day of the experiment (food and water deprivation), and then provided with food on the second and third days. % sugar solution and water were provided simultaneously, providing experience with 2% sugar. Afterwards, on the 4th day, food and water were withheld for 18 hours, and then on the 5th day of the experiment, 2% sugar solution and water were provided simultaneously for 3 hours, allowing free choice. To measure the mouse's intake, the weight of the solution and bottle were recorded before and after the 3-hour test.
설탕 선호는 (설탕 용액 섭취량/총 액체 섭취량) x 100으로 계산하였다.Sugar preference was calculated as (sugar solution intake/total liquid intake) x 100.
설탕 선호 시험 (Sucrose preference test, SPT)은 우울감으로 인해 발생하는 무쾌감증의 판단 척도가 된다. 일반 물과 1% 내외의 설탕 용액을 쥐에게 제공해 어떤 액체를 더 선호하는 지 보는 실험으로, 정상쥐는 설탕 용액을 더 선호하는 경향을 보이나, 우울감/무쾌감증을 느끼는 쥐는 물과 설탕 용액 사이의 선호도 차이가 별로 없었다.The sugar preference test (SPT) is a measure of anhedonia caused by depression. This was an experiment in which rats were given regular water and a 1% sugar solution to see which liquid they preferred. Normal rats tended to prefer the sugar solution, but depressed/anhedonic rats had a preference for the sugar solution. There was little difference in preference.
실험 결과, 도 7에 나타낸 바와 같이 탈람파넬을 투여한 군은 대조군에 비하여 설탕용액에 대한 선호가 높아진 것을 확인할 수 있었다.As a result of the experiment, as shown in Figure 7, it was confirmed that the group administered talampanel had an increased preference for sugar solution compared to the control group.
Claims (19)
- 하기 화학식 1로 표시되는 탈람파넬(talampanel) 또는 이의 약학적으로 허용가능한 염을 포함하는 스트레스 및 우울증 관련 질환 예방 또는 치료용 약학 조성물:Pharmaceutical composition for preventing or treating diseases related to stress and depression, comprising talampanel or a pharmaceutically acceptable salt thereof represented by the following formula (1):[화학식 1][Formula 1]
- 제1항에 있어서,According to paragraph 1,상기 스트레스 및 우울증 관련 질환은 우울증, 스트레스, 수술 후 스트레스 증후군, 스트레스에 의한 군발성 두통, 스트레스에 의한 편두통, 스트레스에 의한 원인불명의 통증, 스트레스로 인한 불면증, 기억 장애, 인지 장애 및 주의력 장애로 이루어진 군으로부터 선택되는 어느 하나인, 약학 조성물.The above stress and depression-related diseases include depression, stress, post-surgical stress syndrome, cluster headaches due to stress, migraines due to stress, unexplained pain due to stress, insomnia due to stress, memory impairment, cognitive impairment, and attention disorder. A pharmaceutical composition selected from the group consisting of:
- 제2항에 있어서,According to paragraph 2,상기 스트레스 및 우울증 관련 질환은,The above stress and depression-related diseases are:우울증인, 약학 조성물.Pharmaceutical composition for depression.
- 제1항에 있어서, 상기 탈람파넬(talampanel) 또는 이의 약학적으로 허용가능한 염은 지속적 혹은 반복적인 스트레스의 축적 억제 효과를 나타내는 것인, 약학 조성물.The pharmaceutical composition according to claim 1, wherein talampanel or a pharmaceutically acceptable salt thereof exhibits an effect of suppressing the accumulation of continuous or repetitive stress.
- 하기 화학식 1로 표시되는 탈람파넬(talampanel) 또는 이의 식품학적으로 허용가능한 염을 포함하는 스트레스 및 우울증 관련 질환 예방 또는 개선용 식품 조성물.A food composition for preventing or improving diseases related to stress and depression, comprising talampanel or a foodologically acceptable salt thereof represented by the following formula (1).[화학식 1][Formula 1]
- 제5항에 있어서,According to clause 5,상기 스트레스 및 우울증 관련 질환은 우울증, 스트레스, 수술 후 스트레스 증후군, 스트레스에 의한 군발성 두통, 스트레스에 의한 편두통, 스트레스에 의한 원인불명의 통증, 스트레스로 인한 불면증, 기억 장애, 인지 장애 및 주의력 장애로 이루어진 군으로부터 선택되는 어느 하나인, 식품 조성물.The above stress and depression-related diseases include depression, stress, post-surgical stress syndrome, cluster headaches due to stress, migraines due to stress, unexplained pain due to stress, insomnia due to stress, memory impairment, cognitive impairment, and attention disorder. A food composition selected from the group consisting of:
- 제6항에 있어서,According to clause 6,상기 스트레스 및 우울증 관련 질환은,The above stress and depression-related diseases are:우울증인, 식품 조성물.Food composition for depression.
- 치료학적으로 유효한 양의 하기 화학식 1로 표시되는 탈람파넬(talampanel), 또는 이의 약학적으로 허용 가능한 염을 이를 필요로 하는 개체에게 투여하는 단계를 포함하는 스트레스 및 우울증 관련 질환의 예방 또는 치료 방법:A method for preventing or treating diseases related to stress and depression, comprising the step of administering a therapeutically effective amount of talampanel, or a pharmaceutically acceptable salt thereof, represented by the following formula (1) to an individual in need thereof:[화학식 1][Formula 1]
- 제8항에 있어서,According to clause 8,상기 스트레스 및 우울증 관련 질환은 우울증, 스트레스, 수술 후 스트레스 증후군, 스트레스에 의한 군발성 두통, 스트레스에 의한 편두통, 스트레스에 의한 원인불명의 통증, 스트레스로 인한 불면증, 기억 장애, 인지 장애 및 주의력 장애로 이루어진 군으로부터 선택되는 어느 하나인, 치료 방법.The above stress and depression-related diseases include depression, stress, post-surgical stress syndrome, cluster headaches due to stress, migraines due to stress, unexplained pain due to stress, insomnia due to stress, memory impairment, cognitive impairment, and attention disorder. A treatment method selected from the group consisting of:
- 제8항에 있어서,According to clause 8,상기 스트레스 및 우울증 관련 질환은,The above stress and depression-related diseases are:우울증인, 치료 방법.Depression, treatment methods.
- 제8항에 있어서, 상기 탈람파넬(talampanel) 또는 이의 약학적으로 허용가능한 염은 지속적 혹은 반복적인 스트레스의 축적 억제 효과를 나타내는 것인, 치료 방법. The treatment method according to claim 8, wherein talampanel or a pharmaceutically acceptable salt thereof exhibits an effect of suppressing the accumulation of continuous or repetitive stress.
- 스트레스 및 우울증 관련 질환의 예방 또는 치료를 위한 의약을 제조하기 위한 하기 화학식 1로 표시되는 탈람파넬(talampanel), 또는 이의 약학적으로 허용 가능한 염의 용도:Use of talampanel, or a pharmaceutically acceptable salt thereof, represented by the following formula (1) for manufacturing a medicine for the prevention or treatment of stress and depression-related diseases:[화학식 1][Formula 1]
- 제12항에 있어서,According to clause 12,상기 스트레스 및 우울증 관련 질환은 우울증, 스트레스, 수술 후 스트레스 증후군, 스트레스에 의한 군발성 두통, 스트레스에 의한 편두통, 스트레스에 의한 원인불명의 통증, 스트레스로 인한 불면증, 기억 장애, 인지 장애 및 주의력 장애로 이루어진 군으로부터 선택되는 어느 하나인, 용도.The above stress and depression-related diseases include depression, stress, post-surgical stress syndrome, cluster headaches due to stress, migraines due to stress, unexplained pain due to stress, insomnia due to stress, memory impairment, cognitive impairment, and attention disorder. Any one of the uses selected from the group consisting of:
- 제12항에 있어서,According to clause 12,상기 스트레스 및 우울증 관련 질환은,The above stress and depression-related diseases are:우울증인, 용도.For depression, use.
- 제12항에 있어서, 상기 탈람파넬(talampanel) 또는 이의 약학적으로 허용가능한 염은 지속적 혹은 반복적인 스트레스의 축적 억제 효과를 나타내는 것인, 용도. The use according to claim 12, wherein talampanel or a pharmaceutically acceptable salt thereof exhibits an effect of suppressing the accumulation of continuous or repetitive stress.
- 스트레스 및 우울증 관련 질환의 예방 또는 치료에 사용하기 위한 하기 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용 가능한 염을 포함하는 약학 조성물:A pharmaceutical composition comprising a compound represented by the following formula (1), or a pharmaceutically acceptable salt thereof, for use in the prevention or treatment of diseases related to stress and depression:[화학식 1][Formula 1]
- 제16항에 있어서,According to clause 16,상기 스트레스 및 우울증 관련 질환은 우울증, 스트레스, 수술 후 스트레스 증후군, 스트레스에 의한 군발성 두통, 스트레스에 의한 편두통, 스트레스에 의한 원인불명의 통증, 스트레스로 인한 불면증, 기억 장애, 인지 장애 및 주의력 장애로 이루어진 군으로부터 선택되는 어느 하나인, 약학 조성물.The above stress and depression-related diseases include depression, stress, post-surgical stress syndrome, cluster headaches due to stress, migraines due to stress, unexplained pain due to stress, insomnia due to stress, memory impairment, cognitive impairment, and attention disorder. A pharmaceutical composition selected from the group consisting of:
- 제16항에 있어서,According to clause 16,상기 스트레스 및 우울증 관련 질환은,The above stress and depression-related diseases are:우울증인, 약학 조성물.Pharmaceutical composition for depression.
- 제16항에 있어서, 상기 탈람파넬(talampanel) 또는 이의 약학적으로 허용가능한 염은 지속적 혹은 반복적인 스트레스의 축적 억제 효과를 나타내는 것인, 약학 조성물.The pharmaceutical composition according to claim 16, wherein talampanel or a pharmaceutically acceptable salt thereof exhibits an effect of suppressing the accumulation of continuous or repetitive stress.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2022-0145184 | 2022-11-03 | ||
| KR1020220145184A KR20240063495A (en) | 2022-11-03 | 2022-11-03 | Composition for improvement, prevention or treatment of stress and depression related diseases comprising talampanel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2024096445A1 true WO2024096445A1 (en) | 2024-05-10 |
Family
ID=90930887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2023/016806 WO2024096445A1 (en) | 2022-11-03 | 2023-10-26 | Composition for ameliorating, preventing, or treating stress and depression-related diseases, comprising talampanel |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR20240063495A (en) |
| WO (1) | WO2024096445A1 (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120156260A1 (en) * | 2009-07-31 | 2012-06-21 | Ascendis Pharma A/S | Prodrugs Containing an Aromatic Amine Connected By an Amido Bond to a Linker |
| US20160022642A1 (en) * | 2014-07-25 | 2016-01-28 | Yale University | Compounds Useful for Promoting Protein Degradation and Methods Using Same |
| WO2018169798A1 (en) * | 2017-03-11 | 2018-09-20 | The Regents Of The University Of California | Mitigation of cns disorders by combination therapy using neurosteroids, and ampa blockers |
| WO2021259304A1 (en) * | 2020-06-23 | 2021-12-30 | Antengene (Hangzhou) Biologics Co., Ltd. | Antibodies and methods for treating claudin-associated diseases |
| WO2022159506A1 (en) * | 2021-01-19 | 2022-07-28 | Merit Therapeutics, Inc. | Deuterated cannabidiol compounds |
-
2022
- 2022-11-03 KR KR1020220145184A patent/KR20240063495A/en unknown
-
2023
- 2023-10-26 WO PCT/KR2023/016806 patent/WO2024096445A1/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120156260A1 (en) * | 2009-07-31 | 2012-06-21 | Ascendis Pharma A/S | Prodrugs Containing an Aromatic Amine Connected By an Amido Bond to a Linker |
| US20160022642A1 (en) * | 2014-07-25 | 2016-01-28 | Yale University | Compounds Useful for Promoting Protein Degradation and Methods Using Same |
| WO2018169798A1 (en) * | 2017-03-11 | 2018-09-20 | The Regents Of The University Of California | Mitigation of cns disorders by combination therapy using neurosteroids, and ampa blockers |
| WO2021259304A1 (en) * | 2020-06-23 | 2021-12-30 | Antengene (Hangzhou) Biologics Co., Ltd. | Antibodies and methods for treating claudin-associated diseases |
| WO2022159506A1 (en) * | 2021-01-19 | 2022-07-28 | Merit Therapeutics, Inc. | Deuterated cannabidiol compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20240063495A (en) | 2024-05-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2020149636A1 (en) | Pharmaceutical composition containing aucubin for preventing or treating dry-eye syndrome | |
| BG107185A (en) | Method for the preparation of a medicament for treating sexual dysfunction with apomorphine at specified plasma concentration levels | |
| WO2022244913A1 (en) | Pharmaceutical composition for preventing or treating age-related sarcopenia containing ecklonia cava extract as active ingredient | |
| WO2024106716A1 (en) | Composition for alleviating or treating dementia, containing 2'-fucosyllactose | |
| WO2024096445A1 (en) | Composition for ameliorating, preventing, or treating stress and depression-related diseases, comprising talampanel | |
| AU2015384083B2 (en) | Use of albiflorin or pharmaceutically acceptable salt for prevention and/or treatment of irritable bowel syndrome | |
| WO2017179914A1 (en) | Composition for preventing or treating gout, containing biotin-tagged caffeic acid compound as active ingredient | |
| WO2020184884A1 (en) | Composition for preventing or treating obesity or lipid-related metabolic disorders | |
| WO2023080409A1 (en) | Composition for preventing or alleviating sleep disorder, comprising zizyphus seed powder and rosae multiflorae fructus powder | |
| WO2012091492A2 (en) | Herbal extract, pharmaceutical composition including the same and health functional food including the same | |
| WO2023038258A1 (en) | Novel lactobacillus gasseri lm1065 strain derived from breast milk, and composition for alleviating premenstrual syndrome comprising said strain or culture product thereof | |
| CA2504502A1 (en) | Method of treating colon disturbances with pharmaceutical compositions containing imidazol-1-yl compounds | |
| WO2018208107A1 (en) | Composition for alleviating, preventing, or treating somnipathy or composition for suppressing resistance to benzodiazepine binding site agonist of gaba-a receptor or for alleviating side-effect of benzodiazepine binding site agonist of gaba-a receptor, each composition comprising phloroglucinol as effective ingredient | |
| WO2013085351A1 (en) | Pharmaceutical composition comprising diaminodiphenylsulfone or the pharmaceutically acceptable salts thereof for preventing or treating diseases associated with muscle atrophy | |
| WO2020231030A2 (en) | Composition comprising lactobacillus acidophilus for preventing, alleviating, or treating nervousness, formication, insomnia, vertigo, or fatigue in menopausal women | |
| WO2021141426A1 (en) | Composition for treating fragile x syndrome or related developmental disorders, comprising lisuride compound as active ingredient | |
| WO2019203509A1 (en) | Pharmaceutical composition, comprising agmatine or pharmaceutically acceptable salt thereof, for prevention or treatment of fragile x syndrome | |
| WO2020085612A1 (en) | Pharmaceutical composition for treating depressive disorders and anxiety disorders, containing mixture of creatine and taurine | |
| WO2020085818A1 (en) | Composition for treating fragile x syndrome and related developmental disorders comprising pirenperone compound as active ingredient | |
| WO2019139399A1 (en) | Pharmaceutical composition comprising pi3 kinase inhibitor and cytotoxic anti-cancer agent for preventing or treating cancer | |
| WO2024096261A1 (en) | Composition for preventing or treating autoinflammatory diseases, and uses thereof | |
| AU2020391291B2 (en) | Combination therapy of cycloserine and lithium for the treatment of depression | |
| WO2023211146A1 (en) | Composition containing 2'-fl for ameliorating, preventing, or treating diseases caused by reduction of dopamine | |
| WO2023085664A1 (en) | Composition containing taurodeoxycholic acid or pharmaceutically acceptable salt thereof as active ingredient for preventing or treating viral infectious diseases | |
| JPH01221316A (en) | Cerebral circulatory metabolism-improving agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 23886141 Country of ref document: EP Kind code of ref document: A1 |