WO2016140277A1 - ペプチド - Google Patents
ペプチド Download PDFInfo
- Publication number
- WO2016140277A1 WO2016140277A1 PCT/JP2016/056453 JP2016056453W WO2016140277A1 WO 2016140277 A1 WO2016140277 A1 WO 2016140277A1 JP 2016056453 W JP2016056453 W JP 2016056453W WO 2016140277 A1 WO2016140277 A1 WO 2016140277A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- peptide
- test
- seq
- lsstqaqqsy
- amino acid
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 114
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 15
- 235000013305 food Nutrition 0.000 claims description 34
- 230000008450 motivation Effects 0.000 claims description 25
- 108090001109 Thermolysin Proteins 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 15
- 208000019022 Mood disease Diseases 0.000 claims description 14
- 230000003001 depressive effect Effects 0.000 claims description 13
- 230000002829 reductive effect Effects 0.000 claims description 12
- 208000024891 symptom Diseases 0.000 claims description 10
- 239000000935 antidepressant agent Substances 0.000 claims description 9
- 108700037728 Glycine max beta-conglycinin Proteins 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 8
- 230000001430 anti-depressive effect Effects 0.000 claims description 8
- 229940005513 antidepressants Drugs 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 238000012360 testing method Methods 0.000 description 75
- 239000000725 suspension Substances 0.000 description 28
- 241000699670 Mus sp. Species 0.000 description 20
- 241000699666 Mus <mouse, genus> Species 0.000 description 19
- -1 L-form amino acids Chemical class 0.000 description 18
- GAQNUGISBQJMKO-YFKPBYRVSA-N beta-citrylglutamic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)C(O)(CC(O)=O)CC(O)=O GAQNUGISBQJMKO-YFKPBYRVSA-N 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
- 230000009471 action Effects 0.000 description 16
- 108090000790 Enzymes Proteins 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 15
- 230000007423 decrease Effects 0.000 description 12
- 239000008187 granular material Substances 0.000 description 11
- 230000009182 swimming Effects 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 210000004899 c-terminal region Anatomy 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 244000068988 Glycine max Species 0.000 description 7
- 235000010469 Glycine max Nutrition 0.000 description 7
- 239000005557 antagonist Substances 0.000 description 7
- 230000006399 behavior Effects 0.000 description 7
- 238000012346 open field test Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 238000010998 test method Methods 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 235000009508 confectionery Nutrition 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 208000019901 Anxiety disease Diseases 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 108090000787 Subtilisin Proteins 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 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
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-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
- 244000269722 Thea sinensis Species 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000013361 beverage Nutrition 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
- 230000003247 decreasing effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000012048 forced swim test Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000011535 reaction buffer Substances 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- FGHVSEXHEAUJBT-HFNHQGOYSA-N (z)-but-2-enedioic acid;(5r)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound OC(=O)\C=C/C(O)=O.C1([C@@H]2C3=CC(O)=C(Cl)C=C3CCN(C2)C)=CC=CC=C1 FGHVSEXHEAUJBT-HFNHQGOYSA-N 0.000 description 2
- 239000003140 4 aminobutyric acid A receptor blocking agent Substances 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- IYGYMKDQCDOMRE-QRWMCTBCSA-N Bicculine Chemical compound O([C@H]1C2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-QRWMCTBCSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 108090000511 Dopamine D1 Receptors Proteins 0.000 description 2
- 102000004076 Dopamine D1 Receptors Human genes 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
- 229940090502 GABA A receptor antagonist Drugs 0.000 description 2
- 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 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- UMTDAKAAYOXIKU-UHFFFAOYSA-N N-tert-butyl-3-[4-(2-methoxyphenyl)-1-piperazinyl]-2-phenylpropanamide Chemical compound COC1=CC=CC=C1N1CCN(CC(C(=O)NC(C)(C)C)C=2C=CC=CC=2)CC1 UMTDAKAAYOXIKU-UHFFFAOYSA-N 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000000049 anti-anxiety effect Effects 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- AACMFFIUYXGCOC-UHFFFAOYSA-N bicuculline Natural products CN1CCc2cc3OCOc3cc2C1C4OCc5c6OCOc6ccc45 AACMFFIUYXGCOC-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- IYGYMKDQCDOMRE-UHFFFAOYSA-N d-Bicucullin Natural products CN1CCC2=CC=3OCOC=3C=C2C1C1OC(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-UHFFFAOYSA-N 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000007941 film coated tablet Substances 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229960004801 imipramine Drugs 0.000 description 2
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- 239000008274 jelly 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
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000000474 nursing effect Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000003727 serotonin 1A antagonist Substances 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000005556 structure-activity relationship Methods 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
- 235000013616 tea 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
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-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
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002942 Apathy Diseases 0.000 description 1
- 241000193389 Bacillus thermoproteolyticus Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 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
- 206010012374 Depressed mood Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 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
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 102000027484 GABAA receptors Human genes 0.000 description 1
- 108091008681 GABAA receptors Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- 102000017911 HTR1A Human genes 0.000 description 1
- 101150015707 HTR1A gene Proteins 0.000 description 1
- 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 1
- 239000004166 Lanolin Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol 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
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 235000006468 Thea sinensis Nutrition 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000002180 anti-stress Effects 0.000 description 1
- 235000013527 bean curd Nutrition 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000005978 brain dysfunction Effects 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
- 235000012970 cakes Nutrition 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 235000016213 coffee Nutrition 0.000 description 1
- 235000013353 coffee beverage Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 235000012495 crackers Nutrition 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 108010093406 dopamine D1A receptor Proteins 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 108010025899 gelatin film Proteins 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000001341 hydroxy propyl starch Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 235000015255 meat loaf Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- IWVKTOUOPHGZRX-UHFFFAOYSA-N methyl 2-methylprop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.COC(=O)C(C)=C IWVKTOUOPHGZRX-UHFFFAOYSA-N 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
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- 235000013557 nattō Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000019520 non-alcoholic beverage Nutrition 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000031787 nutrient reservoir activity Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 235000020333 oolong tea Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- IXSOLZFHKQSRHW-UHFFFAOYSA-L potassium sodium dodecyl sulfate Chemical compound [Na+].[K+].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O IXSOLZFHKQSRHW-UHFFFAOYSA-L 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000020991 processed meat Nutrition 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 235000011962 puddings Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 235000021058 soft food Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000006068 taste-masking agent Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 238000007492 two-way ANOVA Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 235000020125 yoghurt-based beverage Nutrition 0.000 description 1
Images
Classifications
-
- 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
- A23L11/00—Pulses, i.e. fruits of leguminous plants, for production of food; Products from legumes; Preparation or treatment thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/415—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
-
- 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
- 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
- A23L33/17—Amino acids, peptides or proteins
-
- 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
- A23L33/30—Dietetic or nutritional methods, e.g. for losing weight
-
- 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
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
Definitions
- the present invention relates to a novel peptide.
- the present invention also relates to medicines and foods containing the peptides.
- Patent Document 1 discloses a peptide exhibiting antidepressant activity derived from wheat gluten. However, there are no known peptides that can improve motivation.
- An object of the present invention is to provide a novel peptide having an action for improving reduced motivation, depression, or depressive mood disorder, and a medicine and a food containing the peptide.
- the present inventor has intensively studied to solve the above problems. As a result, the inventors succeeded in isolating a novel peptide having an action for improving motivation, depression, or depressive mood disorder. Based on such knowledge, the present invention has been completed through further studies.
- the present invention includes the following aspects.
- Item 1 (i) amino acid sequence LSSTQAQQSY (SEQ ID NO: 1), (Ii) amino acid sequence LSSTQAQQSW (SEQ ID NO: 6), or (iii) amino acid sequence LSSTQAQQSF (SEQ ID NO: 7), The peptide which consists of either.
- Item 2 A peptide consisting of the amino acid sequence LSSTQAQQSY (SEQ ID NO: 1), derived from a thermolysin digest of soybean beta-conglycinin protein.
- a pharmaceutical composition comprising the peptide according to Item 3, Item 1 or 2 as an active ingredient.
- Item 4 The pharmaceutical composition according to Item 3, which is a therapeutic agent for reduced motivation, an antidepressant, depressive mood disorder or a symptom based thereon.
- Item 6 A food characterized by adding the peptide according to Item 1, Item 2 or Item 2.
- Item 7 The food according to Item 5 or 6 for improving reduced motivation, depression or depressive mood disorder or a condition based thereon.
- Item 9 Use of the peptide according to Item 1 or 2 for improving motivation, depression, depressive mood disorder or symptoms based thereon.
- the pharmaceutical composition and food containing the peptide of the present invention as an active ingredient have high antidepressant action / motivation action, have low side effects and are suitable for long-term use.
- the pharmaceutical composition and food of the present invention are effective for oral administration.
- natural short-chain peptides can be ingested as food and do not lead to disease, but it can be expected that an individual having a problem of reduced motivation will ingest disease as food.
- the peptide of the present invention is an enzyme digest of soybean beta-conglycinin protein, side effects are not a problem.
- soybean beta-conglycinin protein is contained in a large amount in soybean, so that it can be produced at low cost.
- test method of the tail suspension test (Tail suspension test) is shown. 24-30 g male ddY mice were used as test animals.
- B The test method of the forced swimming test (Forced swim test) is shown. The test methods of the tail suspension test (Tail suspension test) and the forced swimming test (Forced swim test) are shown. Test 30 minutes after oral administration (perpeptideou (po)) of test substance (enzyme digest (digest) or peptide (peptide)), in case of tail suspension test 0 to 6 minutes or forced swimming test In this case, the immobility time from 0 to 8 minutes was measured.
- EPM elevated plus-maze test
- Open OF test Open OF test
- mouth which orally administered the peptide is shown.
- the examination results of the structure-activity relationship of the peptides are shown by the results of the tail suspension test.
- the examination result of the action mechanism of the enzyme digest using an antagonist is shown by the result of the tail suspension test.
- the examination result of the action mechanism of the peptide using the antagonist is shown by the result of the tail suspension test.
- a model of an action mechanism in which an expected antidepressant action (motivation improving action) occurs is shown.
- the result of an elevated plus maze test in mice orally administered with an enzyme digest is shown.
- the result of an elevated plus maze test in mice orally administered with peptides is shown.
- mouth which orally administered the peptide is shown.
- mouth which orally administered the peptide is shown.
- the peptide of the present invention comprises (i) LSSTQAQQSY (SEQ ID NO: 1), (ii) amino acid sequence LSSTQAQQSW (SEQ ID NO: 6), (iii) amino acid sequence LSSTQAQQSF (SEQ ID NO: 7), A peptide having 10 residues.
- the amino acids constituting the peptide are L-form amino acids, D-form amino acids, or DL-form amino acids (the racemate and any amino acid in which either enantiomer is excessive if the D-form and L-form amino acids are mixed). Any of them may be used, and a peptide consisting only of L-form amino acids or a D-form amino acid, particularly a peptide consisting only of an L-form amino acid, is preferred.
- the peptide used in the present invention when it contains two or more asymmetric carbons, it may be in the form of each enantiomer or diastereomer or a mixture of these in any ratio. Separation of enantiomers or diastereomers can be carried out using a normal column. An optically active column is used, or an optically active group is introduced and optically resolved in the form of a derivative, and then the optically active group is removed. Any known method such as a method or optical resolution by forming a salt with an optically active acid or base can be used.
- the peptide can have modifications.
- the amino terminus (N-terminus) of the peptide can be any one having a modification such as a free amino group (NH 2- ) or an acetyl group (CH 3 CO-).
- the carboxy terminus (C terminus) of the peptide can be any having a modification such as a free carboxyl group (—COOH) or an amide group.
- the amino acid residue of the peptide can be any one that is not modified, or has a modification such as a phosphate group or a sugar chain.
- the peptide of the present invention can be a salt (acid addition salt or base salt).
- Acid addition salts include inorganic salts such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, perchloric acid, citric acid, succinic acid, maleic acid, fumaric acid, malic acid, tartaric acid, p-toluenesulfonic acid And salts of organic acids such as benzenesulfonic acid, methanesulfonic acid and trifluoroacetic acid.
- the base salt include alkali metal salts such as sodium, potassium and lithium, and alkaline earth metal salts such as calcium and magnesium.
- the peptide of the present invention can be a solvate.
- Solvates include solvates such as water (in the case of hydrates), methanol, ethanol, isopropanol, acetic acid, tetrahydrofuran, acetone, dimethylformamide, dimethyl sulfoxide, dimethylacetamide, acetamide, ethylene glycol, propylene glycol, and dimethoxyethane. Things.
- the peptide of the present invention in particular, the peptide consisting of the amino acid sequence LSSTQAQQSY (SEQ ID NO: 1) can be obtained by hydrolysis of the main storage protein beta-conglycinin ( ⁇ -conglycinin, ⁇ -CG) protein of soybean.
- Thermolysin is a known proteolytic enzyme (protease) derived from the thermostable bacterium Bacillus thermoproteolyticus (EC 3.4.24.4). Thermolysin can be used as a food additive in Japan. As thermolysin, commercially available products such as reagent grade and food additive grade can be used.
- the substrate to be hydrolyzed by thermolysin is not particularly limited as long as it contains soybean ⁇ -CG protein.
- soybean itself pomace obtained by extracting soybean oil from soybean (also referred to as meal or defatted soybean), purified beta-conglycinin protein and the like can be mentioned.
- the reaction temperature can be appropriately selected from 30 to 70 ° C, 30 to 40 ° C, 40 to 70 ° C, 50 to 65 ° C, and the like.
- the reaction time can be appropriately selected from about 30 minutes to 48 hours, about 1 to 10 hours, and about 2 to 8 hours.
- the pH at which the reaction is carried out can be appropriately selected from about pH 6.5 to 8.5 and pH 7 to 8. In one preferred embodiment, the reaction can be performed for about 2 to 8 hours under conditions of a temperature of about 30 to 40 ° C. and a pH of 6.5 to 8.5 (particularly about pH 7.5).
- the peptide of the present invention may not be obtained under conditions where hydrolysis is excessively performed.
- thermolysin is deactivated by heating to a temperature at which thermolysin is deactivated (for example, heating at a temperature exceeding 80 ° C. for about 5 to 60 minutes).
- reaction product of hydrolysis can be used as it is, and the peptide as an active ingredient can be separated and used by purification.
- the peptide of the present invention can also be obtained by peptide synthesis. That is, in a liquid phase method or a solid phase method, which is a commonly used method for peptide synthesis, a method using an active ester such as HBTU, a raw material having a reactive carboxyl group and a raw material having a reactive amino group, or carbodiimide In a peptide synthesis such as a method using a coupling agent such as When the resulting condensate has a protecting group, it can also be produced by removing the protecting group.
- the C-terminal carboxyl group is a chlorotrityl resin, chloromethyl resin, oxymethyl resin, p- It is bound to a carrier such as an alkoxybenzyl alcohol resin.
- the condensation reaction is carried out in the presence of a condensing agent such as carbodiimide or using an N-protected amino acid active ester or peptide active ester.
- the protecting group is removed, but in the case of the solid phase method, the bond between the C-terminus of the peptide and the resin is further cleaved.
- the peptides of the present invention are purified according to conventional methods. Examples thereof include ion exchange chromatography, reverse phase liquid chromatography, affinity chromatography and the like. Synthesis of the synthesized peptide is analyzed by a protein sequencer that reads the amino acid sequence from the C-terminal by the Edman degradation method, GC-MS, or the like.
- the peptide of the present invention can also be synthesized by an enzymatic method (see WO2003 / 010307).
- the peptide of the present invention is effective in improving or treating reduced motivation, depression, depressive mood disorders or conditions (symptoms) based on them.
- “decreased motivation” and “depressive mood disorder” include impulses of the mind (mind) such as lack of motivation and interest or interest in anything.
- “Depressed motivation” and “depressive mood disorder” are not limited to a disease or condition caused by depression, but a condition of a person who is not diagnosed as depression such as aging (aging) and stress (eg, adaptation disorder). Is also included.
- the effect of treating or improving motivation is, for example, the immobility time of the tail suspension test and forced swimming test used for the evaluation of antidepressant drugs in mice. Can be evaluated as an index.
- the peptide of the present invention also has an anxiolytic action and is effective in improving or treating anxiety.
- the anxiolytic action can be evaluated by, for example, an elevated plus maze test or an open field test. Depression is primarily caused by stress, feeling that there is no support around it, brain dysfunction occurs, the way things are viewed negatively, a vicious circle of overestimating the load and feeling more stress is created This peptide, which exhibits anti-stress action, removes the cause of decreased motivation, depression, or depressed mood disorder or conditions (symptoms) based on them. I can expect that.
- the peptide of the present invention can be provided as a pharmaceutical composition or a food (food composition).
- the route of administration of the peptide of the present invention or a product containing the peptide is not particularly limited, and any of oral administration, parenteral administration, and rectal administration can be adopted, orally or parenterally. Can be administered. Among these, oral administration is preferable from the viewpoint of high effect.
- the dose of this peptide varies depending on the type of compound, the method of administration, the condition and age of the person being administered, etc., but is usually 0.01 mg / kg to 500 mg / kg, preferably 0.05 mg / kg 100 mg / kg, more preferably 0.1-30 mg / kg.
- the peptide (active ingredient) of the present invention is usually administered in the form of a pharmaceutical composition prepared by mixing with a pharmaceutical carrier.
- a pharmaceutical carrier a substance that is commonly used in the pharmaceutical field and does not react with the peptide of the present invention is used.
- the peptide of the present invention can be used as a medicine or food per se, or alone or together with a suitable non-toxic carrier for ingestion, diluent or excipient (tablet, uncoated tablet, dragee, effervescent tablet, Film-coated tablets, chewable tablets, etc.), capsules, troches, powders, fine granules, granules, solutions, suspensions, emulsions, pastes, creams, injections (amino acid infusions, electrolyte infusions, etc.) Or a preparation for food or medicine such as sustained release preparations such as enteric tablets, capsules and granules.
- the content of the peptide in the food can be appropriately selected, but is generally in the range of 0.01 to 100% by weight.
- Examples of the dosage form include tablets, capsules, granules, powders, syrups, suspensions, suppositories, ointments, creams, gels, patches, inhalants, injections, and the like. These preparations are prepared according to a conventional method.
- the liquid preparation can be dissolved or suspended in water or other appropriate solvent when used. Tablets and granules can be coated by a known method.
- injection it is prepared by dissolving the peptide of the present invention in water. If necessary, it can be dissolved in physiological saline or glucose solution, and a buffer or preservative can be added. it can.
- These preparations may contain the peptide of the present invention in a proportion of 0.01% to 100% by weight, preferably 1 to 90% by weight. These formulations can also contain other ingredients of therapeutic value.
- an active ingredient and excipient components such as lactose, starch, crystalline cellulose, calcium lactate, anhydrous silicic acid and the like are mixed to form a powder, or if necessary, sucrose, Add a binder such as hydroxypropylcellulose and polyvinylpyrrolidone, a disintegrant such as carboxymethylcellulose and carboxymethylcellulose calcium, and wet or dry granulate to form granules.
- these powders and granules can be tableted as they are or with the addition of lubricants such as magnesium stearate and talc.
- granules or tablets should be coated with an enteric solvent base such as hydroxypropylmethylcellulose phthalate or methacrylic acid-methyl methacrylate polymer and coated with an enteric solvent preparation, or with ethylcellulose, carnauba wax, hardened oil, etc. You can also.
- an enteric solvent base such as hydroxypropylmethylcellulose phthalate or methacrylic acid-methyl methacrylate polymer and coated with an enteric solvent preparation, or with ethylcellulose, carnauba wax, hardened oil, etc. You can also.
- powders or granules are filled into hard capsules, or active ingredients are dissolved as they are or dissolved in glycerin, polyethylene glycol, sesame oil, olive oil, etc., and then coated with a gelatin film to form soft capsules. Can do.
- an active ingredient and a sweetener such as sucrose, sorbitol, and glycerin are dissolved in water to add a transparent syrup, further essential oil, ethanol, etc. to make an elixir, Gum arabic, tragacanth, polysorbate 80, sodium carboxymethyl cellulose and the like can be added to form an emulsion or suspension.
- a taste-masking agent, a coloring agent, a preservative and the like can be added to these liquid preparations as desired.
- Examples of foods that can be prepared by adding and blending the peptides of the present invention include so-called health foods, functional foods, dietary supplements, supplements, foods for specified health use, foods for sick people and combination foods for sick people (Ministry of Health, Labor and Welfare, Special foods) or elderly foods (Ministry of Health, Labor and Welfare, special foods), uncoated tablets, film-coated tablets, sugar-coated tablets, granules, powders, tablets, capsules (either hard capsules or soft capsules) Including chewable type, syrup type, and drink type.
- the preparation of food containing the peptide according to the present invention can be carried out by a method known per se.
- ⁇ Method> (Tail suspension test) As shown in FIG. 1A, after suspending a mouse (ddY mouse, male, 24-30 g) with the tail and showing escape behavior first, the time to disappear and to show immobility (immobility time (Immobility time)) was measured. The test was performed 30 minutes after administration of the test substance (0 minutes), and the immobility time from 0 minutes to 6 minutes was measured (FIG. 2).
- an antidepressant such as imipramine
- this immobility time decreases. Therefore, when a decrease in immobility time is observed, it can be evaluated as having an antidepressant-like action.
- An immobility state is considered a despair state, and a decrease in the immobility time is an indicator of an improvement of the despair state, that is, an increase in motivation.
- FIG. 1B (Forced swim test) As shown in Fig. 1B, put a mouse (ddY mouse, male, 24-30g) in a non-escapeable aquarium, load forced swimming, show escape behavior first, then lose power and show no movement The time to become (immobility time) was measured. The test was performed 30 minutes after administration of the test substance (0 minutes), and the immobility time from 0 minutes to 8 minutes was measured (FIG. 2).
- an antidepressant such as imipramine reduces this immobility time. Therefore, when a decrease in immobility time is observed, it can be evaluated as having an antidepressant-like action.
- An immobility state is considered a despair state, and a decrease in the immobility time is an indicator of an improvement of the despair state, that is, an increase in motivation.
- the elevated plus maze consists of two open arms (25cm x 5cm) and two closed arms (25cm x 5cm x 15cm), which are connected to a central platform 50cm above the floor (See FIG. 3A).
- EPM Electronicted plus maze
- the elevated plus maze consists of two open arms (25cm x 5cm) and two closed arms (25cm x 5cm x 15cm), which are connected to a central platform 50cm above the floor (See FIG. 3A).
- EPM Extended plus maze
- mice (ddY mice, male, 24-30 g) were administered test substances 30 minutes before the test and 30 minutes later on a central platform facing one of the open arms.
- the test was started with a mouse. Cumulative time spent in open arms (time in open arms), number of visits to open arms (visit to open arms), total number of visits to any arm (total visits) was recorded. The percentage of time spent in the open arm and the percentage of visits to the open arm were calculated as an indicator of anxiety.
- a test substance was administered to mice (ddY mice, male, 24-30 g) 30 minutes before the test, and 30 minutes later, the test substance was placed in an open field to start the test.
- mice ddY mice, male, 24-30 g
- the test substance was placed in an open field to start the test.
- the percentage of exploration behavior in the center of the circle (Time in 12cm circle) and the number of stays in the center circle (Visit ⁇ ⁇ in ⁇ ⁇ 12 ⁇ cm ⁇ circle)) evaluated.
- ⁇ Production example> Enzyme digest
- ⁇ -CG 1: 100 (weight ratio, final concentration of ⁇ -CG: 20 mg / ml), and attached in the attached buffer. Reaction was performed.
- the enzymes and reaction conditions used were as follows: (I) Thermolysin (Seikagaku Corporation); reaction temperature: 37 ° C., reaction time: 5 hours; reaction buffer: pH 7.5 (Ii) Subtilisin (Sigma); reaction temperature: 37 ° C., reaction time: 5 hours; reaction buffer: pH 7.5 (Iii) Smithzyme (Seikagaku Corporation); reaction temperature: 50 ° C., reaction time: 5 hours; reaction buffer: pH 7.0.
- the sample was boiled (100 ° C., 10 minutes) to stop the enzyme reaction.
- LSSTQAQQSY (SEQ ID NO: 1), LSSTQAQQS (SEQ ID NO: 2), SSTQAQQSY (SEQ ID NO: 3), LSSTQ (SEQ ID NO: 4) and AQQSY (SEQ ID NO: 5) were synthesized by a conventional method.
- Example 1 Tail suspension test (enzyme digest)
- a tail suspension test was performed using mice that were orally administered with 30 mg / kg of ⁇ -CG thermolysin digest, 30 mg / kg of ⁇ -CG subtilisin digest, and 30 mg / kg of ⁇ -CG sumizyme digest, respectively.
- N 16-20.
- Administration of only saline as a solvent was used as a control (hereinafter the same).
- thermolysin digest was observed to reduce immobility time compared to the control.
- Example 2 tail suspension test (enzyme digest)
- Example 3 Forced swimming test (enzyme digest)
- Example 4 Tail suspension test (peptide)
- Example 5 Forced swimming test (peptide)
- mice administered with 0.3 mg / kg or 1 mg / kg (n 12-13).
- the LSSTQAQQSY peptide LSSTQAQQSY was contained in 266 mg (21 mol%) per 100 g of the digest in the ⁇ -CG thermolysin digest.
- the peptide LSSTQAQQSY was not detected in the subtilisin digest and the Smithzyme digest.
- Example 6 Structure-activity relationship of peptides
- Peptide LSSTQAQQSY (SEQ ID NO: 2) with 1 residue deleted from the C-terminal of peptide LSSTQAQQSY, STSQAQQSY (SEQ ID NO: 3) with 1 residue deleted from peptide LSSTQAQQSY, N-terminal half of peptide LSSTQAQQSY Mice that were orally administered 0.3 mg / kg with the test substance of peptide LSSTQ (SEQ ID NO: 4) consisting of 5 residues and peptide AQQSY (SEQ ID NO: 5) consisting of 5 residues in the C-terminal half of peptide LSSTQAQQSY
- Example 7 Investigation of mechanism of action using antagonist (enzyme digest)
- a tail suspension test was conducted using mice that were orally administered (po) in combination with 30 mg / kg of a thermolysin digest of ⁇ -CG and antagonists of various receptors.
- As antagonists serotonin 5-HT1A receptor antagonist WAY100135 (dose: 10 mg / kg), dopamine D1 receptor SCH23390 (dose: 30 ⁇ g / kg) and GABA-A receptor antagonist bicuculline (dose) : 30 mg / kg).
- Example 8 Investigation of mechanism of action using antagonist (peptide)
- a tail suspension test was conducted using mice that were orally administered (po) with the peptide LSSTQAQQSY 0.3 mg / kg in combination with various receptor antagonists.
- As antagonists serotonin 5-HT1A receptor antagonist WAY100135 (dose: 10 mg / kg), dopamine D1 receptor SCH23390 (dose: 30 ⁇ g / kg) and GABA-A receptor antagonist bicuculline (dose) : 30 mg / kg).
- Example 9 Elevated plus maze test (enzyme digest)
- Example 10 Elevated plus maze test (peptide)
- Example 11 Open field test (peptide)
- mice administered with 0.1 mg / kgm, 0.3 mg / kg or 1 mg / kg (n 4-5).
- Example 12 tail suspension test (peptide)
- Peptide LSSTQAQQSY (SEQ ID NO: 1)
- C-terminal amidated peptide LSSTQAQQSY (LSSTQAQQSY-NH 2 )
- peptide LSSTQAQQSY (SEQ ID NO: 6)
- peptide LSSTQAQQSW (SEQ ID NO: 7)
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Botany (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Agronomy & Crop Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Pediatric Medicine (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
本出願は、2015年3月2日に出願された、日本国特許出願第2015-040368号明細書(その開示全体が参照により本明細書中に援用される)に基づく優先権を主張する。
(ii)アミノ酸配列LSSTQAQQSW(配列番号6)、または
(iii)アミノ酸配列LSSTQAQQSF(配列番号7)、
のいずれかからなるペプチド。
のアミノ酸配列からなる、残基数が10のペプチドである。
(尾懸垂試験(Tail suspension test))
図1Aに示すようにマウス(ddYマウス、雄、24~30g)を尾でつり下げて、初めに逃避行動を示した後、気力をなくし無動を示すようになる時間(無動時間(Immobility time))を測定した。試験物質の投与から30分後に試験を行い(0分)、0分から6分間の無動時間を測定した(図2)。
図1Bに示すようにマウス(ddYマウス、雄、24~30g)を逃避不可能な水槽内に入れ強制水泳を負荷して、初めに逃避行動を示した後、気力をなくし無動を示すようになる時間(無動時間(Immobility time))を測定した。試験物質の投与から30分後に試験を行い(0分)、0分から8分間の無動時間を測定した(図2)。
高架式十字迷路は、2つのオープンアーム(open arm; 25cm×5cm)と2つのクローズドアーム(closed arm; 25cm×5cm×15cm)からなり、それらのアームは床から50cm高くなった中央プラットフォームと結合している(図3A参照)。高い位置にあるにも関わらず、クローズドアームの周りには囲いがあるために、マウスは安全に歩行する事ができる。一方、オープンアームの周囲は開放されていて囲いがないために、オープンアームを歩行するマウスは高い位置から転落するという不安感を感じる。そのために、マウスがオープンアームにいる時間が長いほど、あるいは進入回数が多いほど、マウスの不安感は緩和されており、抗不安活性の指標となる。
マウスは通常円の周辺部を好み、中央部への探索行動は極めて少ない(図3B参照)。高架式十字迷路実験の場合と同様に、マウスの円中心部での探索行動の割合が高いほど、マウスの不安感は緩和されており、抗不安活性の指標となる。
試験により得られたたデータを、平均(Mean)と標準誤差(Standard error of the mean、SEM)との和で表した。データを1方向または2方向ANOVAにより解析し、引き続いて多重比較のためのFisher試験を行った。p<0.05の場合(図中、”*”)若しくはp<0.01の場合(図中、”**”)に、有意差ありと判定した。
(酵素消化物)
精製したβコングリシニン(β-CG)タンパク質と消化酵素とを、酵素:β-CG=1:100(重量比、β-CGの終濃度:20 mg/ml)で混合し、添付のバッファー中で反応を行った。
(i)サーモリシン(生化学工業);反応温度:37℃、反応時間:5時間;反応バッファー:pH 7.5
(ii)ズブチリシン(Sigma);反応温度:37℃、反応時間:5時間;反応バッファー:pH 7.5
(iii)スミザイム(生化学工業);反応温度:50℃、反応時間:5時間;反応バッファー:pH 7.0。
定法により、ペプチドLSSTQAQQSY(配列番号1)、LSSTQAQQS(配列番号2)、SSTQAQQSY(配列番号3)、LSSTQ(配列番号4)及びAQQSY(配列番号5)を合成した。
(実施例1:尾懸垂試験(酵素消化物))
β-CGのサーモリシン消化物30mg/kg、β-CGのズブチリシン消化物30mg/kg及びβ-CGのスミザイム消化物30mg/kgをそれぞれ試験物質として経口投与したマウスを用いて、尾懸垂試験を行った(n=16-20)。溶媒の生理食塩水のみの投与を、対照とした(以下、同様。)。
β-CGのサーモリシン消化物を試験物質として、10mg/kg又は30mg/kgを経口投与したマウスを用いて、尾懸垂試験を行った(n=11-12)。
β-CGのサーモリシン消化物を試験物質として、30mg/kg又は100mg/kgを投与したマウスを用いて、強制水泳試験を行った(n=6)。
ペプチドLSSTQAQQSYを試験物質として、0.1mg/kg、0.3mg/kg、1mg/kg又は3mg/kgを投与したマウスを用いて、尾懸垂試験を行った(n=8-10)。
ペプチドLSSTQAQQSYを試験物質として、0.3mg/kg又は1mg/kgを投与したマウスを用いて、強制水泳試験を行った(n=12-13)。
UPLC-ESI-MSにより、β-CGのサーモリシン消化物、β-CGのズブチリシン消化物及びβ-CGのスミザイム消化物に含まれるペプチドLSSTQAQQSYを定量した。
ペプチドLSSTQAQQSYのC末端を1残基欠失させたペプチドLSSTQAQQS(配列番号2)、ペプチドLSSTQAQQSYのN末端を1残基欠失させたペプチドSSTQAQQSY(配列番号3)、ペプチドLSSTQAQQSYのN末端側半分の5残基からなるペプチドLSSTQ(配列番号4)及びペプチドLSSTQAQQSYのC末端側半分の5残基からなるペプチドAQQSY(配列番号5)のそれぞれを試験物質として、0.3mg/kgを経口投与したマウスを用いて、尾懸垂試験を行った(n=5-6又は18-19)。
β-CGのサーモリシン消化物30mg/kgと、各種受容体のアンタゴニストとを併用して経口投与(p.o.)したマウスを用いて、尾懸垂試験を行った。アンタゴニストとしては、セロトニン5-HT1A受容体のアンタゴニストのWAY100135(投与量:10mg/kg)、ドーパミンD1受容体のSCH23390(投与量:30μg/kg)及びGABA-A受容体のアンタゴニストのbicuculline(投与量:30mg/kg)の3種類を用いた。
ペプチドLSSTQAQQSY 0.3mg/kgと、各種受容体のアンタゴニストとを併用して経口投与(p.o.)したマウスを用いて、尾懸垂試験を行った。アンタゴニストとしては、セロトニン5-HT1A受容体のアンタゴニストのWAY100135(投与量:10mg/kg)、ドーパミンD1受容体のSCH23390(投与量:30μg/kg)及びGABA-A受容体のアンタゴニストのbicuculline(投与量:30mg/kg)の3種類を用いた。
β-CGのサーモリシン消化物を試験物質として、3mg/kg、10mg/kg又は30mg/kgを経口投与したマウスを用いて、高架式十字迷路試験を行った(n=11)。
ペプチドLSSTQAQQSYを試験物質として、0.1mg/kgm、0.3mg/kg又は1mg/kgを投与したマウスを用いて、高架式十字迷路試験を行った(n=18-19)。
ペプチドLSSTQAQQSYを試験物質として、0.1mg/kgm、0.3mg/kg又は1mg/kgを投与したマウスを用いて、オープンフィールド試験を行った(n=4-5)。
ペプチドLSSTQAQQSY(配列番号1)、C末端をアミド化したペプチドLSSTQAQQSY(LSSTQAQQSY-NH2)、ペプチドLSSTQAQQSY(配列番号6)及びペプチドLSSTQAQQSW(配列番号7)を試験物質として、0.3mg/kgを経口投与したマウスを用いて、尾懸垂試験を行った(n=11-12)
Claims (9)
- (i)アミノ酸配列LSSTQAQQSY(配列番号1)、
(ii)アミノ酸配列LSSTQAQQSW(配列番号6)、または
(iii)アミノ酸配列LSSTQAQQSF(配列番号7)、
のいずれかからなるペプチド。 - 大豆のベータコングリシニンタンパク質のサーモリシン消化物に由来する、アミノ酸配列LSSTQAQQSY(配列番号1)からなるペプチド。
- 請求項1または2に記載のペプチドを有効成分とする医薬組成物。
- 意欲低下治療薬、抗うつ薬またはうつ的気分障害もしくはそれらに基づく症状の治療薬である、請求項3に記載の医薬組成物。
- 請求項1または2に記載のペプチドを含有する食品。
- 請求項1または2に記載のペプチドを添加することを特徴とする食品。
- 意欲低下、うつ病またはうつ的気分障害もしくはそれらに基づく状態を改善するための、請求項5または6に記載の食品。
- 請求項1または2に記載のペプチドを、意欲低下、うつ病またはうつ的気分障害もしくはそれらに基づく症状の患者またはその予備群に投与する工程を含む、意欲低下、うつ病またはうつ的気分障害もしくはそれらに基づく症状を改善もしくは治療する方法。
- 意欲低下、うつ病またはうつ的気分障害もしくはそれらに基づく症状を改善するための、請求項1または2に記載のペプチドの使用。
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES16758970T ES2935913T3 (es) | 2015-03-02 | 2016-03-02 | Péptido |
US15/554,890 US10280202B2 (en) | 2015-03-02 | 2016-03-02 | Peptide |
EP22173496.5A EP4094588A1 (en) | 2015-03-02 | 2016-03-02 | Peptide |
JP2017503694A JP6667781B2 (ja) | 2015-03-02 | 2016-03-02 | ペプチド |
EP16758970.4A EP3266794B1 (en) | 2015-03-02 | 2016-03-02 | Peptide |
US17/718,789 US20230011813A1 (en) | 2015-03-02 | 2022-04-12 | Peptide |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015-040368 | 2015-03-02 | ||
JP2015040368 | 2015-03-02 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/554,890 A-371-Of-International US10280202B2 (en) | 2015-03-02 | 2016-03-02 | Peptide |
US201916357772A Continuation | 2015-03-02 | 2019-03-19 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2016140277A1 true WO2016140277A1 (ja) | 2016-09-09 |
Family
ID=56848850
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2016/056453 WO2016140277A1 (ja) | 2015-03-02 | 2016-03-02 | ペプチド |
Country Status (5)
Country | Link |
---|---|
US (2) | US10280202B2 (ja) |
EP (2) | EP4094588A1 (ja) |
JP (2) | JP6667781B2 (ja) |
ES (1) | ES2935913T3 (ja) |
WO (1) | WO2016140277A1 (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018047852A1 (en) * | 2016-09-07 | 2018-03-15 | Kyoto University | Peptides and peptide conjugates for treating mental disorders |
US10280202B2 (en) | 2015-03-02 | 2019-05-07 | Kyoto University | Peptide |
WO2023114846A1 (en) | 2021-12-15 | 2023-06-22 | Digestome Therapeutics, Inc. | Uses of therapeutic peptides |
WO2024117210A1 (ja) * | 2022-12-01 | 2024-06-06 | 国立大学法人京都大学 | ペプチド含有組成物 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022168413A1 (ja) * | 2021-02-04 | 2022-08-11 | ユーハ味覚糖株式会社 | デプレスタチン含有組成物の製造方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009247270A (ja) * | 2008-04-04 | 2009-10-29 | Rohto Pharmaceut Co Ltd | ダイズペプチド含有固形製剤 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003010307A1 (en) | 2001-07-26 | 2003-02-06 | Ajinomoto Co., Inc. | Peptide synthase gene, peptide synthase and process for producing dipeptide |
JP4792563B2 (ja) | 2005-09-29 | 2011-10-12 | 日本サプリメント株式会社 | 新規なオピオイド活性ペプチド、新規な抗不安ペプチド |
EP2130533A4 (en) * | 2007-04-05 | 2010-04-21 | J Oil Mills Inc | ATARACTIC AND FUNCTIONAL FOOD |
US20100210564A1 (en) * | 2009-02-02 | 2010-08-19 | Kyoto University | Drug or food containing a peptide |
JP5582433B2 (ja) * | 2009-03-24 | 2014-09-03 | 国立大学法人名古屋大学 | 機能性ペプチドを表すルールの抽出法、機能性ペプチドの設計法及び調製法、ポリペプチド又はポリペプチド含有組成物の評価法、並びに機能性ペプチド |
KR20130059335A (ko) | 2010-04-07 | 2013-06-05 | 고쿠리츠 다이가쿠 호진 교토 다이가쿠 | 생리 활성 펩티드 |
JP6098929B2 (ja) | 2013-02-22 | 2017-03-22 | 国立大学法人京都大学 | 抗うつ剤又は抗不安剤 |
WO2016140277A1 (ja) | 2015-03-02 | 2016-09-09 | 国立大学法人京都大学 | ペプチド |
-
2016
- 2016-03-02 WO PCT/JP2016/056453 patent/WO2016140277A1/ja active Application Filing
- 2016-03-02 ES ES16758970T patent/ES2935913T3/es active Active
- 2016-03-02 JP JP2017503694A patent/JP6667781B2/ja active Active
- 2016-03-02 US US15/554,890 patent/US10280202B2/en active Active
- 2016-03-02 EP EP22173496.5A patent/EP4094588A1/en active Pending
- 2016-03-02 EP EP16758970.4A patent/EP3266794B1/en active Active
-
2019
- 2019-11-25 JP JP2019212045A patent/JP7141642B2/ja active Active
-
2022
- 2022-04-12 US US17/718,789 patent/US20230011813A1/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009247270A (ja) * | 2008-04-04 | 2009-10-29 | Rohto Pharmaceut Co Ltd | ダイズペプチド含有固形製剤 |
Non-Patent Citations (4)
Title |
---|
EIKO HATAKEYAMA ET AL.: "Modulating effects of soy protein isolate and soy protein hydrolysate on human brain function", DAIZU TANPAKUSHITSU KENKYU, vol. 6, 2003, pages 147 - 152, XP009505695 * |
See also references of EP3266794A4 * |
THE MINISTRY OF AGRICULTURE, FORESTRY AND FISHERIES OF JAPAN RESEARCH COUNCIL JIMUKYOKU ET AL., NIPPON-GATA SHOKUHIN SOZAI SEIBUN NO NO KINO CHOSETSU KOKA NO KAISEKI, SHOKUHIN NO ANZENSEI OYOBI KINOSEI NI KANSURU KENKYU-KINOSEI, no. 446, 2008, pages 352 - 361 * |
TSUYOSHI OTSUKA ET AL.: "Tanjitsu Joken ni Okeru Mouse no Jodo Kanren Kodo no Eiyogaku- teki Seigyo", JOURNAL OF PET NUTRITION, vol. 17, 2014, pages 54 - 55, XP055481615 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10280202B2 (en) | 2015-03-02 | 2019-05-07 | Kyoto University | Peptide |
WO2018047852A1 (en) * | 2016-09-07 | 2018-03-15 | Kyoto University | Peptides and peptide conjugates for treating mental disorders |
WO2023114846A1 (en) | 2021-12-15 | 2023-06-22 | Digestome Therapeutics, Inc. | Uses of therapeutic peptides |
WO2024117210A1 (ja) * | 2022-12-01 | 2024-06-06 | 国立大学法人京都大学 | ペプチド含有組成物 |
Also Published As
Publication number | Publication date |
---|---|
EP4094588A1 (en) | 2022-11-30 |
US20230011813A1 (en) | 2023-01-12 |
JP2020040982A (ja) | 2020-03-19 |
EP3266794A1 (en) | 2018-01-10 |
JPWO2016140277A1 (ja) | 2018-01-11 |
US20180044386A1 (en) | 2018-02-15 |
EP3266794B1 (en) | 2022-11-30 |
US10280202B2 (en) | 2019-05-07 |
JP7141642B2 (ja) | 2022-09-26 |
JP6667781B2 (ja) | 2020-03-18 |
EP3266794A4 (en) | 2018-08-22 |
ES2935913T3 (es) | 2023-03-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7141642B2 (ja) | ペプチド | |
JPWO2013129220A1 (ja) | ペプチドを含む医薬または食品 | |
WO2011126054A1 (ja) | 生理活性ペプチド | |
JP2023126910A (ja) | 治療用ペプチド | |
JP6957033B2 (ja) | ペプチド | |
JP6958864B2 (ja) | ペプチド | |
WO2021107080A1 (ja) | ペプチド | |
WO2020218450A1 (ja) | ペプチド、組成物、及びグレリン分泌促進剤 | |
CA3099658C (en) | Peptide, composition, and method for treating, preventing, or ameliorating mood disorder | |
JP7398716B2 (ja) | ペプチド、組成物、及び、気分障害を治療、予防、又は改善する方法 | |
JP7339650B2 (ja) | ペプチド | |
WO2011148972A1 (ja) | 生理活性ペプチドを含む医薬組成物 | |
JP2018184367A (ja) | ペプチド | |
JP2015209400A (ja) | 新規トリペプチド及びペプチド含有組成物、並びにそれらの使用、それらを有効成分として含有する摂食抑制剤、抗肥満剤、動脈弛緩剤、血圧降下剤、メタボリックシンドローム予防改善剤、又は食欲調節用の食品組成物 |
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: 16758970 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2017503694 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 15554890 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REEP | Request for entry into the european phase |
Ref document number: 2016758970 Country of ref document: EP |