US20200215086A1 - Anti-fatigue composition - Google Patents
Anti-fatigue composition Download PDFInfo
- Publication number
- US20200215086A1 US20200215086A1 US16/825,017 US202016825017A US2020215086A1 US 20200215086 A1 US20200215086 A1 US 20200215086A1 US 202016825017 A US202016825017 A US 202016825017A US 2020215086 A1 US2020215086 A1 US 2020215086A1
- Authority
- US
- United States
- Prior art keywords
- histidine
- fatigue
- vitamin
- group
- ingestion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 94
- 230000002929 anti-fatigue Effects 0.000 title claims description 56
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims abstract description 394
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 217
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims abstract description 173
- 229940011671 vitamin b6 Drugs 0.000 claims abstract description 172
- 235000019158 vitamin B6 Nutrition 0.000 claims abstract description 169
- 239000011726 vitamin B6 Substances 0.000 claims abstract description 169
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 claims abstract description 102
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 claims abstract description 101
- 108010087806 Carnosine Proteins 0.000 claims abstract description 101
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 claims abstract description 101
- 229940044199 carnosine Drugs 0.000 claims abstract description 101
- 235000013305 food Nutrition 0.000 abstract description 105
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 230
- 229960002885 histidine Drugs 0.000 description 222
- 230000037406 food intake Effects 0.000 description 117
- 206010016256 fatigue Diseases 0.000 description 99
- 238000012360 testing method Methods 0.000 description 66
- 230000000694 effects Effects 0.000 description 65
- 235000012054 meals Nutrition 0.000 description 47
- 208000010340 Sleep Deprivation Diseases 0.000 description 44
- 239000000126 substance Substances 0.000 description 27
- 230000007423 decrease Effects 0.000 description 26
- 230000007062 hydrolysis Effects 0.000 description 24
- 238000006460 hydrolysis reaction Methods 0.000 description 24
- 230000006742 locomotor activity Effects 0.000 description 24
- 150000003839 salts Chemical class 0.000 description 23
- 238000000034 method Methods 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 18
- 238000005259 measurement Methods 0.000 description 17
- 239000002775 capsule Substances 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 230000006399 behavior Effects 0.000 description 12
- 238000007427 paired t-test Methods 0.000 description 12
- 238000012795 verification Methods 0.000 description 11
- 239000000523 sample Substances 0.000 description 10
- 229940088594 vitamin Drugs 0.000 description 10
- 229930003231 vitamin Natural products 0.000 description 10
- 235000013343 vitamin Nutrition 0.000 description 10
- 239000011782 vitamin Substances 0.000 description 10
- 150000003722 vitamin derivatives Chemical class 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 229940024606 amino acid Drugs 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 238000009395 breeding Methods 0.000 description 9
- 230000001488 breeding effect Effects 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 239000000796 flavoring agent Substances 0.000 description 9
- 235000019634 flavors Nutrition 0.000 description 9
- 235000015110 jellies Nutrition 0.000 description 9
- 239000008274 jelly Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 230000001149 cognitive effect Effects 0.000 description 8
- 239000008187 granular material Substances 0.000 description 8
- 239000002002 slurry Substances 0.000 description 8
- 230000008859 change Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 230000003340 mental effect Effects 0.000 description 7
- 230000008450 motivation Effects 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 229920002678 cellulose Polymers 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 235000009508 confectionery Nutrition 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 235000015165 citric acid Nutrition 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 229940099112 cornstarch Drugs 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 230000035622 drinking Effects 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 108010016626 Dipeptides Proteins 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 208000019914 Mental Fatigue Diseases 0.000 description 4
- 244000269722 Thea sinensis Species 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 239000013068 control sample Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 230000003111 delayed effect Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- NHZMQXZHNVQTQA-UHFFFAOYSA-N pyridoxamine Chemical compound CC1=NC=C(CO)C(CN)=C1O NHZMQXZHNVQTQA-UHFFFAOYSA-N 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010041349 Somnolence Diseases 0.000 description 3
- 229920002472 Starch Polymers 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
- 230000000996 additive effect Effects 0.000 description 3
- 229940000635 beta-alanine Drugs 0.000 description 3
- 230000003920 cognitive function Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 235000011194 food seasoning agent Nutrition 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000008123 high-intensity sweetener Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000013615 non-nutritive sweetener Nutrition 0.000 description 3
- 235000008160 pyridoxine Nutrition 0.000 description 3
- 239000011677 pyridoxine Substances 0.000 description 3
- 230000000284 resting effect Effects 0.000 description 3
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000000341 volatile oil Substances 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 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
- GUBGYTABKSRVRQ-PICCSMPSSA-N D-Maltose 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)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- 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 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 2
- 239000004158 L-cystine Substances 0.000 description 2
- 235000019393 L-cystine Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 description 2
- 235000006468 Thea sinensis Nutrition 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 235000013405 beer Nutrition 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- 235000013539 calcium stearate Nutrition 0.000 description 2
- 239000008116 calcium stearate Substances 0.000 description 2
- QWJSAWXRUVVRLH-UHFFFAOYSA-M choline bitartrate Chemical compound C[N+](C)(C)CCO.OC(=O)C(O)C(O)C([O-])=O QWJSAWXRUVVRLH-UHFFFAOYSA-M 0.000 description 2
- 229960004874 choline bitartrate Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- RVRCFVVLDHTFFA-UHFFFAOYSA-N heptasodium;tungsten;nonatriacontahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[W].[W].[W].[W].[W].[W].[W].[W].[W].[W].[W] RVRCFVVLDHTFFA-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 235000008164 pyridoxal Nutrition 0.000 description 2
- 239000011674 pyridoxal Substances 0.000 description 2
- 229960003581 pyridoxal Drugs 0.000 description 2
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 2
- 235000007682 pyridoxal 5'-phosphate Nutrition 0.000 description 2
- 239000011589 pyridoxal 5'-phosphate Substances 0.000 description 2
- 235000008151 pyridoxamine Nutrition 0.000 description 2
- 239000011699 pyridoxamine Substances 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000004092 self-diagnosis Methods 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 235000019640 taste Nutrition 0.000 description 2
- 235000013616 tea Nutrition 0.000 description 2
- 239000004250 tert-Butylhydroquinone Substances 0.000 description 2
- 235000019281 tert-butylhydroquinone Nutrition 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
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 description 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- LUTLAXLNPLZCOF-UHFFFAOYSA-N 1-Methylhistidine Natural products OC(=O)C(N)(C)CC1=NC=CN1 LUTLAXLNPLZCOF-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
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 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
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108010085443 Anserine Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 235000011960 Brassica ruvo Nutrition 0.000 description 1
- CLXSALIMWSGGMU-UHFFFAOYSA-N CC1=C(O)C(C=O)=C(CO)C=N1.CC1=C(O)C(CN)=C(CO)C=N1.CC1=C(O)C(CO)=C(CO)C=N1 Chemical compound CC1=C(O)C(C=O)=C(CO)C=N1.CC1=C(O)C(CN)=C(CO)C=N1.CC1=C(O)C(CO)=C(CO)C=N1 CLXSALIMWSGGMU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- OABOXRPGTFRBFZ-IMJSIDKUSA-N Cys-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(O)=O OABOXRPGTFRBFZ-IMJSIDKUSA-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
- 241000283073 Equus caballus Species 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 compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 241000282412 Homo Species 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
- SLRNWACWRVGMKD-UHFFFAOYSA-N L-anserine Natural products CN1C=NC(CC(NC(=O)CCN)C(O)=O)=C1 SLRNWACWRVGMKD-UHFFFAOYSA-N 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 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
- BRMWTNUJHUMWMS-LURJTMIESA-N N(tele)-methyl-L-histidine Chemical compound CN1C=NC(C[C@H](N)C(O)=O)=C1 BRMWTNUJHUMWMS-LURJTMIESA-N 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
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000210053 Potentilla elegans Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 240000005049 Prunus salicina Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000533293 Sesbania emerus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 241000282898 Sus scrofa Species 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
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 240000006909 Tilia x europaea Species 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 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
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- HXXFSFRBOHSIMQ-VFUOTHLCSA-N alpha-D-glucose 1-phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(O)=O)[C@H](O)[C@@H](O)[C@@H]1O HXXFSFRBOHSIMQ-VFUOTHLCSA-N 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
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000037354 amino acid metabolism Effects 0.000 description 1
- MYYIAHXIVFADCU-QMMMGPOBSA-N anserine Chemical compound CN1C=NC=C1C[C@H](NC(=O)CC[NH3+])C([O-])=O MYYIAHXIVFADCU-QMMMGPOBSA-N 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 235000020279 black tea Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 235000013532 brandy Nutrition 0.000 description 1
- 230000003139 buffering effect 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
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 235000013353 coffee beverage Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 108010004073 cysteinylcysteine Proteins 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000015897 energy drink Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 235000019414 erythritol Nutrition 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
- 238000000605 extraction Methods 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 229950010772 glucose-1-phosphate Drugs 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 125000001072 heteroaryl group Chemical group 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
- -1 imidazoyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000009018 li Nutrition 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 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
- 235000010355 mannitol Nutrition 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 239000001683 mentha spicata herb oil Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 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
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000020333 oolong tea Nutrition 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
- 230000008433 psychological processes and functions Effects 0.000 description 1
- 235000011962 puddings Nutrition 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- ZMJGSOSNSPKHNH-UHFFFAOYSA-N pyridoxamine 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(CN)=C1O ZMJGSOSNSPKHNH-UHFFFAOYSA-N 0.000 description 1
- 125000002181 pyridoxine group Chemical group 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
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 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
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 235000019614 sour taste Nutrition 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 235000011496 sports drink Nutrition 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 230000003867 tiredness Effects 0.000 description 1
- 208000016255 tiredness Diseases 0.000 description 1
- 238000005891 transamination reaction Methods 0.000 description 1
- 235000015192 vegetable juice Nutrition 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000015041 whisky Nutrition 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
- A23L2/56—Flavouring or bittering agents
-
- 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
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
- A23L2/66—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
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- 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
- A23L33/175—Amino acids
-
- 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
- A23L33/18—Peptides; Protein hydrolysates
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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 anti-fatigue compositions, foods which contain such a composition, and uses of such a composition.
- Histidine is one kind of basic amino acid, and is an essential amino acid having an imidazoyl group as a heteroaromatic ring in the side chain. Histidine is an amino acid admitted as a food additive, and contained in many foods. For example, histidine is added as a seasoning or flavor-adjusting agent aiming at firm taste, prevention of diffusion of flavor, and the like, and the content thereof is about 50 mg/100 ml at maximum. In relation to the known function of histidine, an anti-fatigue composition containing histidine or histidine hydrochloride is known (see JP-A-2006-137706, which is incorporated herein by reference in its entirety).
- Vitamin B6 is one kind of water-soluble vitamin and is a pyridine derivative.
- Vitamin B6 includes pyridoxine, pyridoxal and pyridoxamine, and they are mutually convertible. They are phosphorylated in the body into pyridoxal 5′-phosphate (PLP) and pyridoxamine 5′-phosphoate, and function as a coenzyme of an enzyme involved in amino acid metabolism such as transamination reaction, decarboxylation reaction and the like.
- PRP pyridoxal 5′-phosphate
- pyridoxamine 5′-phosphoate phosphorylated in the body into pyridoxal 5′-phosphate (PLP) and pyridoxamine 5′-phosphoate, and function as a coenzyme of an enzyme involved in amino acid metabolism such as transamination reaction, decarboxylation reaction and the like.
- vitamin B6 was determined to have the following functions in the “functional claims for food and supplement” issued by EFSA (European Food Safety Authority) (see EFSA Journal 2010; 8(10):1759, which is incorporated herein by reference in its entirety).
- EFSA European Food Safety Authority
- Carnosine is a dipeptide wherein histidine and ⁇ alanine are bonded, and is contained in animal-derived foods in large amounts. Carnosine is mainly present in muscles and brain, and a buffering action, an antioxidation action and the like are known (see Amino san no kagaku to saishin ouyou gijiyutsu p. 272-282 CMC Publishing Co., Ltd. 2008, which is incorporated herein by reference in its entirety). It has also been reported that imidazole dipeptide which is a mixture of carnosine and anserine (dipeptide wherein 1 methylhistidine and ⁇ alanine are bonded) shows an anti-fatigue effect (see Journal of Clinical and Experimental Medicine, vol. 228, No. 6, p. 722-726, 2009, which is incorporated herein by reference in its entirety).
- the present invention aims to provide a histidine-containing food capable of affording a sufficient anti-fatigue effect even at a low histidine content, and the like.
- the present invention provides:
- An anti-fatigue composition comprising (1) histidine and (2) vitamin B6 and/or carnosine in combination.
- (1-1) A method of improving fatigue, comprising administering (1) an effective amount of histidine and (2) an effective amount of vitamin B6 and/or carnosine to a subject in need thereof.
- composition for improving fatigue comprising (1) histidine and (2) vitamin B6 and/or carnosine in combination.
- composition of the above-mentioned (1) comprising histidine and vitamin B6 in combination.
- composition for improving fatigue comprising histidine and vitamin B6 in combination.
- composition of the above-mentioned (1) comprising histidine and carnosine in combination.
- (3-1) A method of improving fatigue, comprising administering an effective amount of histidine and an effective amount of carnosine to a subject in need thereof.
- composition for improving fatigue comprising histidine and carnosine in combination.
- a container-packed food comprising (1) histidine and (2) vitamin B6 and/or carnosine.
- a food comprising (1) histidine and (2) vitamin B6 and/or carnosine, which is in a unit package form per meal.
- (31) The food of any of the above-mentioned (21)-(29), which is in the form of powder, tablet, granule or capsule.
- a container-packed drink comprising (1) histidine and (2) vitamin B6 and/or carnosine.
- Fatigue (mental fatigue, physical fatigue) can be improved by ingesting the composition of the present invention, comprising (1) histidine and (2) vitamin B6 and/or carnosine. Since the present invention contains amino acid (peptide) and vitamin as active ingredients, it has less fear of causing side effects and is superior in safety, and can also be consecutively used everyday.
- FIG 1A shows the protocol of generating a fatigue model by burden of insufficient sleep, for the measurement of locomotor activities in the dark phase.
- FIG. 1B shows cumulative locomotor activities for the former half (6 hr) of the dark phase. *: t-test, p ⁇ 0.05.
- FIG. 2A shows the protocol for generating a fatigue model by burden of insufficient sleep, for the measurement of short-working memory.
- FIG. 2B shows the measurement results of alternation behavior. ***: t-test, p ⁇ 0.001.
- FIG. 3A shows the protocol for verifying the effect of the ingestion of histidine (His) and/or test substance X on the improvement of a decrease in the locomotor activities in the dark phase (fatigue index) of mouse after burden of insufficient sleep.
- His histidine
- test substance X test substance X
- FIG. 3B shows cumulative locomotor activities for the former half (6 hr) of the dark phase when histidine (His) and/or vitamin B6 (VB6) are used.
- His histidine
- VB6 vitamin B6
- FIG. 3C shows cumulative locomotor activities for the former half (6 hr) of the dark phase when histidine (His) and/or carnosine are used. *: Tukey's multiple test, p ⁇ 0.05.
- FIG. 4A shows the protocol for verifying the effect of the ingestion of histidine (His) and/or vitamin B6 (VB6) on the change of short-working memory (fatigue index) of mouse after burden of insufficient sleep.
- His histidine
- VB6 vitamin B6
- FIG. 4B shows the measurement results of alternation behavior. **: Tukey's multiple test, p ⁇ 0.01. *: Tukey's multiple test, p ⁇ 0.05.
- His histidine
- VB6 vitamin B6
- FIG. 5B shows the measurement results of alternation behavior. **: Tukey's multiple test, p ⁇ 0.01. *: Tukey's multiple test, p ⁇ 0.05.
- His histidine
- VB6 vitamin B6
- FIG. 6B shows the measurement results of locomotor activities in the dark phase.
- * Tukey's multiple test, p ⁇ 0.05 vs VB6 group.
- # Tukey's multiple test, p ⁇ 0.05 vs solvent group.
- ⁇ t Tukey's multiple test, p ⁇ 0.1 vs solvent group.
- ⁇ Tukey's multiple test, p ⁇ 0.1 vs His group.
- Tukey's multiple test p ⁇ 0.1 vs VB6 group.
- FIG. 6C shows the measurement results of locomotor activities in 4 hr to 5 hr after the start of the dark phase.
- # Tukey's multiple test, p ⁇ 0.05 vs solvent group.
- ⁇ Tukey's multiple test, p ⁇ 0.1 vs His group.
- Tukey's multiple test p ⁇ 0.1 vs VB6 group.
- His histidine
- VB6 vitamin B6
- FIG. 7B shows the measurement results of alternation behavior. *: Tukey's multiple test, p ⁇ 0.05.
- His histidine
- VB6 vitamin B6
- FIG. 8B shows the measurement results of locomotor activities in the dark phase.
- FIG. 9A shows the protocol for verifying the anti-fatigue effect of histidine (His) ingestion in test subjects feeling fatigue and a decrease in the quality of sleep.
- FIG. 9B shows variation of T scores in POMS. *: paired t-test, p ⁇ 0.05.
- FIG. 9C shows variation of each index in VAS before cognitive functioning test (CogHealth). *: paired t-test, p ⁇ 0.05.
- FIG. 9D shows variation in the reaction time in cognitive functioning test. *: paired t-test, p ⁇ 0.05.
- FIG. 9E shows variation of each index in VAS after cognitive functioning test. *: paired t-test, p ⁇ 0.05.
- FIG. 10A shows the protocol for verifying the anti-fatigue effect of single histidine (His) ingestion in test subjects feeling fatigue and a decrease in the quality of sleep.
- His single histidine
- FIG. 10B shows variation of each index in VAS before cognitive functioning test (CogHealth). *: paired t-test, p ⁇ 0.05.
- FIG. 10C shows variation of each index in VAS after cognitive functioning test. *: paired t-test, p ⁇ 0.05.
- His histidine
- VB6 vitamin B6
- FIG. 11B shows the measurement results of alternation behavior. *: Tukey's multiple test, p ⁇ 0.05.
- histidine is an essential amino acid having the following structural formula.
- the histidine used in the present invention may be a substance convertible to histidine by hydrolysis.
- the “substance convertible to histidine by hydrolysis” is a substance that affords histidine by hydrolysis (particularly in vivo hydrolysis), and typical examples thereof include proteins and peptides containing histidine as a constituent unit.
- a substance that affords histidine by hydrolysis produces histidine by hydrolysis in the body after ingestion, and is expected to provide an effect similar to that obtained when histidine is ingested from the start.
- the histidine to be used in the present invention may be one extracted and purified from naturally-present animals, plants and the like, or one obtained by a chemical synthesis method, a fermentation method, an enzyme method or a gene recombination method. Any of L-form, D-form, and DL-form can be used. A commercially available one can be utilized and is preferable since it is convenient.
- Vitamin B6 is one kind of water-soluble vitamin having the following structure.
- Vitamin B6 includes pyridoxine, pyridoxal, and pyridoxamine, which are mutually convertible. While the vitamin B6 used in the present invention may be any compound as long as a desired effect can be exhibited, it is preferably pyridoxine.
- the vitamin B6 to be used in the present invention may be one extracted and purified from naturally-present animals, plants and the like, or one obtained by a chemical synthesis method. A commercially available one can be utilized and is preferable since it is convenient.
- Carnosine is a dipeptide having the following structure, wherein histidine and ⁇ alanine are bonded.
- the carnosine to be used in the present invention may be one extracted and purified from naturally-present animals, plants and the like, or one obtained by a chemical synthesis method, a fermentation method, an enzyme method or a gene recombination method. While L-form and D-form (naturally L-form alone) are present due to stereoisomerism, any of them can be used. A commercially available one can be utilized and is preferable since it is convenient.
- the carnosine used in the present invention may be a substance convertible to carnosine by hydrolysis.
- the “substance convertible to carnosine by hydrolysis” is a substance that affords carnosine by hydrolysis (particularly in vivo hydrolysis), and typical examples thereof include proteins and peptides containing carnosine as a constituent unit.
- a substance that affords carnosine by hydrolysis produces carnosine by hydrolysis in the body after ingestion, and is expected to provide an effect similar to that obtained when carnosine is ingested from the start.
- the content of histidine in a composition or food is determined taking note of the weight of histidine and, when a substance convertible to histidine by hydrolysis is used, by converting to histidine.
- the content of histidine in the composition or food is the total weight of the weight of histidine obtained by converting, by hydrolysis, all substances convertible to histidine by hydrolysis, and histidine presented from the start.
- the content of carnosine in a composition or food is determined taking note of the weight of carnosine and, when a substance convertible to carnosine by hydrolysis is used, by converting to carnosine.
- the content of carnosine in the composition or food is the total weight of the weight of carnosine obtained by converting, by hydrolysis, all substances convertible to carnosine by hydrolysis, and carnosine presented from the start.
- Histidine (or substance convertible to histidine by hydrolysis), vitamin B6, and carnosine (or substance convertible to carnosine by hydrolysis) used in the present invention may be in the form of a salt.
- the form of the salt may be, for example, acid addition salt, salt with a base and the like, and pharmacologically acceptable salt is preferable.
- examples of such salt include salts with inorganic acids, salts with organic acids, salts with inorganic bases, and salts with organic bases.
- salt with an inorganic acid examples include salts with hydrohalic acid (hydrochloric acid, hydrobromic acid, hydroiodic acid etc.), sulfuric acid, nitric acid, phosphoric acid, and the like.
- Examples of the salt with an organic acid include salts with formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, maleic acid, fumaric acid, citric acid, and the like.
- salt with an inorganic base examples include salts with alkali metals such as sodium, potassium, lithium and the like, salts with alkaline earth metals such as calcium, magnesium and the like, salt with ammonium and the like.
- Examples of the salt with an organic base include salts with ethylenediamine, propylenediamine, ethanolamine, monoalkylethanolamine, dialkylethanolamine, diethanolamine, triethanolamine and the like.
- histidine “substance convertible to histidine by hydrolysis” and a salt thereof are hereinafter generically referred to as histidine
- carnosine “substance convertible to carnosine by hydrolysis” and a salt thereof are hereinafter generically referred to as carnosine.
- One embodiment of the present invention is an anti-fatigue composition containing (1) histidine and (2) vitamin B6/or carnosine in combination and, particularly, an anti-fatigue composition containing histidine and vitamin B6 in combination, and an anti-fatigue composition containing histidine and carnosine in combination are provided.
- Another embodiment of the present invention is a method of improving fatigue, comprising administering (1) an effective amount of histidine, and (2) vitamin B6 and/or an effective amount of carnosine to a subject in need thereof and, particularly, a method of improving fatigue, comprising administering (1) an effective amount of histidine and (2) an effective amount of vitamin B6 to a subject in need thereof, and a method of improving fatigue, comprising administering (1) an effective amount of histidine, and (2) an effective amount of carnosine to a subject in need thereof are provided.
- Another embodiment of the present invention is a composition containing (1) histidine and (2) vitamin B6 and/or carnosine in combination for improving fatigue and, particularly, a composition containing histidine and vitamin B6 in combination for improving fatigue, and a composition containing histidine and carnosine in combination for improving fatigue are provided.
- the anti-fatigue composition, the method of improving fatigue, and the composition for improving fatigue of the present invention may use histidine in combination with vitamin B6, histidine in combination with carnosine, or histidine in combination with vitamin B6 and carnosine. Preferably, they use histidine in combination with vitamin B6.
- the combination ratio of histidine and vitamin B6 can be appropriately determined within the range where an anti-fatigue effect can be obtained.
- the combination ratio of histidine and carnosine can also be determined appropriately within the range where an anti-fatigue effect can be obtained.
- vitamin B6 and carnosine When both vitamin B6 and carnosine are administered for combined use with histidine, the dose of vitamin B6 and/or carnosine can be reduced as compared to a single administration thereof.
- the administration form of (1) histidine and (2) vitamin B6/or carnosine is not particularly limited, and (1) and (2) only need to be combined at the time of administration.
- Examples of such administration form include:
- “fatigue” is defined to be reduction of performance.
- “fatigue” is intended to mean both mental fatigue and physical fatigue.
- the term “anti-fatigue” or “fatigue improvement” refers to a fatigue recovery action that promptly recovers the body from the state of fatigue, effect of relieving fatigue when physical burden and mental burden (including burden of insufficient sleep and the like) are applied, or an action to relieve stresses felt daily such as copiopia, mental fatigue, or mental insufficiency and the like, and further, improve efficiency of brain work.
- the anti-fatigue composition of the present invention refers to a composition that improves or recovers decline in the ability for activity of the body accompanied by a peculiar sense of discomfort and a desire to rest, caused by excessive mental and psychological activities, or a disease.
- the anti-fatigue effect can be evaluated by a method known per se. Examples of such methods include subjective evaluation methods such as visual analog scale (VAS), Profile of Mood States (POMS) and the like, and objective evaluation methods such as cognitive functioning test .Coghealth (Coghealth: manufactured by Cogstate Ltd., Health Solution, Inc. provide) capable of measuring a brain function which will be decreased due to fatigue and aging.
- VAS visual analog scale
- POMS Profile of Mood States
- cognitive functioning test .Coghealth (Coghealth: manufactured by Cogstate Ltd., Health Solution, Inc. provide) capable of measuring a brain function which will be decreased due to fatigue and aging.
- the level of fatigue can be judged by evaluating whether the test subject shows low scores of positive index (clear thinking, motivation, attentiveness or concentration), or high score of negative index (depression or drowsiness).
- scores are measured before and after continuous ingestion or single ingestion of a test sample for a given period, and the score of positive index significantly increases or the score of negative index significantly decreases after sample ingestion, the fatigue can be evaluated to have been improved.
- one or more indices selected from the group consisting of clear thinking, motivation, attentiveness, concentration, depression and drowsinesscan can be significantly improved by ingesting the composition of the present invention.
- the level of fatigue can be judged by evaluating whether the test subject shows low scores of positive index (vigor), or high score of negative index (anxiety, depression, anger, fatigue or confusion). More specifically, when the score of fatigue factor (F factor) is not less than 16 by subjective evaluation by POMS, the presence of fatigue is admitted.
- F factor fatigue factor
- scores are measured before and after continuous ingestion or single ingestion of a test sample for a given period, and the score of positive index significantly increases or the score of negative index significantly decreases after sample ingestion, the fatigue can be evaluated to have been improved.
- the indices of fatigue and confusion can be significantly improved by ingesting the composition of the present invention.
- the level of fatigue can be judged by evaluating whether the accuracy rate is low or the reaction time is long in a simple reaction or delayed recall. Furthermore, for example, when a test is performed after continuous ingestion of a test sample or placebo for a given period, and the accuracy rate significantly increases or the reaction time significantly decreases in a test sample ingestion group in a simple reaction or delayed recall as compared to placebo ingestion group, the fatigue can be evaluated to have been improved by ingesting the test sample. Particularly, the reaction time in the delayed recall can be significantly lowered by ingesting the composition of the present invention.
- a decrease in performance and recovery of the decrease only need to be measured by a method known per se, after applying a physical burden (treadmill, swimming etc.), mental burden (restraint stress etc.), or composite stress burden including both (insufficient sleep in water bed etc.).
- a data acquisition analysis system containing an infrared sensor e.g., NS-DAS-32 (NeuroScience, Inc) and the like
- NS-DAS-32 NeuroScience, Inc
- measurement is performed after continuous ingestion of a test sample or a control sample for a given period by a target with fatigue induced by various burdens and, when a decrease in the performance (decrease in spontaneous amount and alternation behavior) is improved in a is test sample ingestion group as compared to a control sample ingestion group, the fatigue can be evaluated to have been improved/recovered by the ingestion of the test sample.
- the anti-fatigue composition of the present invention may be solid or semi-solid, or liquid such as powder, tablet, granule, capsule, slurry, solution, jelly, emulsion, and the like.
- a composition containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, as an ingestion amount per meal is provided. From the aspects of eating experiences obtained from known findings (Food Safety Commission of Japan, Feed/Fertilizer, etc.
- the ingestion amount per meal of histidine is preferably not more than 23 g, more preferably not more than 4 g.
- the ingestion amount per meal of histidine can be further reduced and, for example, an anti-fatigue composition containing not more than 3 g, preferably not more than 2 g, of histidine as an ingestion amount per meal can be provided.
- a composition containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, per unit package is provided.
- an anti-fatigue composition packaged as an ingestion amount per meal as one unit is provided.
- the ingestion amount of vitamin B6 per meal is generally less than 300 mg, preferably not more than 100 mg, since ingestion of an amount exceeding this level does not remarkably enhance the anti-fatigue effect.
- the anti-fatigue composition of the present invention can be provided as a food.
- food is a concept widely encompassing oral ingestible matters, and includes not only what is called “food” but also a drink, health aid food, food with health claims, supplement, and the like.
- an anti-fatigue composition provided as food, food such as food in a unit package form per meal and the like, container-packed food, and container-packed drink are sometimes to be generically referred to as the food of the present invention.
- the anti-fatigue composition of the present invention can be provided as an agent.
- the agent excludes pharmaceutical products, and is ingested for a particular purpose, different from those daily ingested to retain nutrition of the body.
- the form of the food of the present invention is not particularly limited, and may be solid or semi-solid, or liquid m such as powder, tablet, granule, slurry, capsule, solution, jelly, emulsion, and the like.
- histidine, and vitamin B6 and/or carnosine to be contained in the food of the present invention is not particularly limited, and may be powder or granule, slurry, tablet confectionery, capsule, solution, jelly, or emulsion. Of these, granule and powder are preferable, in view of easy portability and easy packaging. In addition, solution, jelly, and slurry are also preferable in view of easy ingestion.
- examples of the unit package form per meal include a form that defines a given amount in a pack, package, bottle, etc. in the case of drink, confectionery, jelly, pudding, yogurt, and the like, and package and the like can define a given amount in the case of granular, powdery and slurry foods.
- a form such as a container and the like indicating the ingestion amount per meal can be mentioned.
- confectionery refers to favorite foods such as sweet stuff and the like, which are eaten other than meals, and examples thereof include candy, chewing gum, tablet confectionery, chocolate, shake, ice, and the like.
- the present invention provides a food comprising (1) histidine and (2) vitamin B6/or carnosine, which is in a unit package form per meal, particularly, a food comprising histidine and vitamin B6, which is in a unit package form per meal, and a food comprising histidine and carnosine, which is in a unit package form per meal.
- the food in a unit package form per meal of the present invention may contain histidine and vitamin B6, or histidine and carnosine, or histidine and vitamin B6, and carnosine. Preferred is one containing histidine and vitamin B6.
- the combination ratio of histidine and vitamin B6 can be appropriately determined within the range where an anti-fatigue effect can be obtained.
- the combination ratio of histidine and carnosine can also be determined appropriately within the range where an anti-fatigue effect can be obtained.
- vitamin B6 and carnosine are contained in addition to histidine, the content of vitamin B6 and/or carnosine can be reduced as compared to a single administration thereof.
- a composition containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, as an ingestion amount per meal is provided.
- the ingestion amount per meal of histidine is preferably not more than 23 g, more preferably not more than 4 g.
- the ingestion amount per meal of histidine can be further reduced and, for example, a food containing not more than 3 g, preferably not more than 2 g, of histidine as an ingestion amount per meal can be provided.
- a food containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, per unit package is provided.
- the ingestion amount of vitamin B6 per meal is generally less than 300 mg, preferably not more than 100 mg, since ingestion of an amount exceeding this level does not remarkably enhance the anti-fatigue effect.
- Another embodiment of the present invention is a container-packed food, comprising (1) histidine and (2) vitamin B6 and/or carnosine, particularly a container-packed food comprising histidine and vitamin B6, and a container-packed food comprising histidine and carnosine.
- the “food” in the container-packed food of the present invention is, for example, the above-mentioned anti-fatigue composition provided as food. It can be produced by injecting or filling the food in a desired container.
- the container-packed food of the present invention may contain histidine and vitamin B6, or histidine and carnosine, or histidine and vitamin B6 and carnosine. Preferred is one containing histidine and vitamin B6.
- the combination ratio of histidine and vitamin B6 in the food can be appropriately determined within the range where an anti-fatigue effect can be obtained.
- the combination ratio of histidine and carnosine can also be determined appropriately within the range where an anti-fatigue effect can be obtained.
- a container-packed food containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, as an ingestion amount per meal is provided.
- the ingestion amount per meal of histidine is preferably not more than 23 g, more preferably not more than 4 g.
- the ingestion amount per meal of histidine can be further reduced and, for example, a container-packed food containing not more than 3 g, preferably not more than 2 g, of histidine as an ingestion amount per meal can be provided.
- the ingestion amount of vitamin B6 per meal is generally less than 300 mg, preferably not more than 100 mg, since ingestion of an amount exceeding this level does not remarkably enhance the anti-fatigue effect.
- Another embodiment of the present invention is a container-packed drink, comprising (1) histidine and (2) vitamin B6 and/or carnosine, particularly a container-packed drink comprising histidine and vitamin B6, and a container-packed drink comprising histidine and carnosine.
- the container-packed drink of the present invention is one embodiment of the above-mentioned container-packed food of the present invention.
- the “drink” in the container-packed drink of the present invention includes, for example, the above-mentioned anti-fatigue composition provided as a drink, specifically, drinks such as tea drinks (e.g., green tea, oolong tea, black tea, etc.), alcohol drinks (e.g., beer, wine, sake, distilled spirits, ume (Japanese plum) wine, low-malt beer, whiskey, brandy, etc.), beverage (e.g., sports drinks, isotonic drinks, mineral water, coffee drinks, etc.), juice (e.g., fruit juice, vegetable juice, etc.) and the like, liquid seasoning (e.g., soy sauce, vinegar, liquor, sweet sake for seasoning, soup stock, etc.), liquid supplement (e.g., nutritional supplement drink, beauty drink, energy drink, etc.), and the like. It can be produced by injecting or filling the drink in a desired container.
- the drink includes not only those served as a solution, a suspension and the like, but also those served for drinking
- the container-packed drink of the present invention may contain histidine and vitamin B6, or histidine and carnosine, or histidine and vitamin B6 and carnosine. Preferred is one containing histidine and vitamin B6.
- the combination ratio of histidine and vitamin B6 in the drink can be appropriately determined within the range where an anti-fatigue effect can be obtained.
- the combination ratio of histidine and carnosine can also be determined appropriately within the range where an anti-fatigue effect can be obtained.
- a container-packed drink containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, as an ingestion amount per meal is provided.
- the ingestion amount per meal of histidine is preferably not more than 23 g, more preferably not more than 4 g.
- the ingestion amount per meal of histidine can be further reduced and, for example, a container-packed drink containing not more than 3 g, preferably not more than 2 g, of histidine as an ingestion amount per meal can be provided.
- a drink containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at a concentration of not less than 1 w/v% can be ingested in necessary quantities for necessary times.
- a container-packed drink preferably at not less than 3 w/v%, more preferably not less than 5 w/v%, is provided.
- a container-packed drink generally at not more than 30 w/v%, preferably not more than 20 w/v%, more preferably not more than 17 w/v%, further preferably not more than 10 w/v%, is provided.
- the ingestion amount of vitamin B6 per meal is generally less than 300 mg, preferably not more than 100 mg, since ingestion of an amount exceeding this level does not remarkably enhance the anti-fatigue effect.
- a container to be used for the container-packed food or container-packed drink of the present invention is appropriately selected according to the object.
- a can, bottle, PET bottle, paper container, aluminum pouch, and the like can be mentioned.
- the volume is not particularly limited, and one or more units may be housed in one container wherein ingestion amount per meal is one unit, or concentrated food/drink may be filled in a container.
- histidine, and vitamin B6 and/or carnosine contained in the food of the present invention being “slurry” means that solid histidine, and vitamin B6 and/or carnosine are suspended in a liquid medium. A part of histidine, and vitamin B6 and/or carnosine may be dissolved in the above-mentioned medium.
- the ingestion form (1) histidine and (2) vitamin B6/or carnosine is not particularly limited, and (1) and (2) only need to be combined at the time of ingestion.
- Examples of such administration form include
- Examples of the application target of the food of the present invention include experiment animals such as rodents (e.g., mouse, rat, hamster, guinea pig, and the like), rabbit and the like, pets such as a dog, cat, and the like, domestic animals and poultry such as bovine, swine, goat, horse, sheep, chicken, and the like, primates such as monkey, orangutan, chimpanzee, and the like, humans, and the like, and human is particularly preferable.
- rodents e.g., mouse, rat, hamster, guinea pig, and the like
- rabbit and the like pets
- pets such as a dog, cat, and the like
- domestic animals and poultry such as bovine, swine, goat, horse, sheep, chicken, and the like
- primates such as monkey, orangutan, chimpanzee, and the like
- humans and the like, and human is particularly preferable.
- the dose of the food of the present invention can be appropriately moderated based on the general description of the dose for human, which is described in the present specification, and further considering the body weight or size of the animal, or the condition, sensitivity and the like of the administration subject at the time of administration.
- the food of the present invention is preferably food with health claims, more preferably food for improving fatigue.
- the food of the present invention can contain various additives in an attempt to provide the same in a form easier to take.
- a corrigent, flavor, excipient, lubricant, and the like can be mentioned, and any additive can be utilized as long as addition to food is admitted.
- the corrigent include souring agents such as ascorbic acid, tartaric acid, citric acid, malic acid and salts of these, and the like, sweeteners such as aspartame, stevia, sucralose, glycyrrhizinic acid, thaumatin, acesulfame potassium, saccharin, saccharin sodium and the like, and the like.
- Examples of the flavor include synthetic flavor compounds such as L-menthol and the like, citrus essential oils such as orange, lemon, lime, grapefruit, and the like, plant essential oils such as a flower essential oil, peppermint oil, spearmint oil, spice oil, and the like, and the like.
- Examples of the excipient include lactose, sucrose, D-mannitol, starch, cornstarch, crystalline cellulose, light anhydrous silicic acid, and the like.
- Examples of the lubricant include magnesium stearate, calcium stearate, talc, colloidal silica, and the like.
- CD2F1 mice (9-week-old or older) (CHARLES RIVER LABORATORIES JAPAN, INC) divided into a control group and a group burdened by insufficient sleep, an experiment was performed as shown in the experiment protocol of FIG. 1A .
- the insufficient sleep-burdened group was burdened by insufficient sleep for 24 hr by filling water in the breeding cage at the depth of 0.5 cm.
- the burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr.
- the control group was reared without burden in the home cage. Thereafter, they were transferred into a cage set under a locomotor activity measurement infrared sensor (Digital acquisition system; NS-DAS-32, Neuroscience Inc, Tokyo, Japan) under fasting and water-deprivation.
- the locomotor activities in the former half (6 hr) of the dark phase were measured and the data was collected by a multidigital counter (Neuroscience Inc, Tokyo, Japan).
- CD2F1 mice (9-week-old or older) (CHARLES RIVER LABORATORIES JAPAN, INC) divided into a control group and an insufficient sleep-burdened group, an experiment was performed as shown in the experiment protocol of FIG. 2A .
- the insufficient sleep-burdened group was burdened by insufficient sleep for 48 hr by filling water in the breeding cage at the depth of 0.5 cm.
- the burden was released 6 hr after the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr.
- the control group was reared without burden in the home cage.
- a Y-maze test was performed at 3 hr from the start of the dark phase, and short-working memory was measured.
- CD2F1 mice (9-week-old or older) (CHARLES RIVER LABORATORIES JAPAN, INC) in the group constitution shown in Table 1, the effect was verified as shown in the experiment protocol of FIG. 3A .
- the His group and the combined use group were allowed to drink each solution freely for one week so that the dose of His would be 500 mg/kg/day.
- the test substance X group and the combined use group were made to ingest test substance X mixed in a feed or drinking water for one week so that the ingestion amount of Table 3 would be met.
- As the feed a feed having the composition of Table 2 was used.
- test amount 2. test combined substance X (mg/kg/day) His substance X use vitamin B12 6 x x x vitamin B1 50 x x x vitamin B6 300 x x ⁇ DHA 700 x x x zinc 30 x x x creatine 400 x x x L-carnitine 500 x x x ⁇ -glycero- 600 x x x phosphocholine carnosine 1800 x x ⁇
- the His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 30 mg/kg/day.
- a feed having the composition of Table 5 was used as the feed.
- insufficient sleep was burdened for 48 hr by filling water in the breeding cage at the depth of 0.5 cm.
- the burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, the His group and His+VB6 group were orally administered with His, and the VB6 group and His+VB6 group were orally administered with VB6 at 2 hr from the start of the dark phase after burden of insufficient sleep to achieve the doses in Table 4.
- a Y-maze test was performed at 3 hr from the start of the dark phase, and short-working memory was measured.
- mice (9-10-week-old) in the group is constitution shown in Table 6, the test was performed as shown in the experiment protocol ( FIG. 5A ).
- the His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 7.5 mg/kg/day.
- a feed having the composition of Table 5 was used as the feed.
- insufficient sleep was burdened for 48 hr by filling water in the breeding cage at the depth of 0.5 cm.
- the burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, the His group and His+VB6 group were orally administered with His, and the VB6 group and His+VB6 group were orally administered with VB6 at 2 hr from the start of the dark phase after burden of insufficient sleep to achieve the doses in Table 6.
- a Y-maze test was performed at 3 hr from the start of the dark phase, and short-working memory was measured.
- the His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 7.5 mg/kg/day.
- a feed having the composition of Table 5 was used as the feed.
- the His+VB6 group showed a significant increase as compared to the solvent group, and an increase tendency as compared to the His group and the VB6 group.
- the His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 2.5 mg/kg/day.
- a feed having the composition of Table 5 was used as the feed.
- the His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 2.5 mg/kg/day.
- a feed having the composition of Table 5 was used as the feed.
- the His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 3.0 mg/kg/day.
- a feed having the composition of Table 5 was used as the feed.
- insufficient sleep was burdened for 48 hr by filling water in the breeding cage at the depth of 0.5 cm.
- the burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, the His group and His+VB6 group were orally administered with His, and the VB6 group and His+VB6 group were orally administered with VB6 at 2 hr from the start of the dark phase after burden of insufficient sleep to achieve the doses in Table 8.
- a Y-maze test was performed at 3 hr from the start of the dark phase, and short-working memory was measured.
- a histidine and vitamin B6-containing tablet having the following combination is produced by tableting according to a conventional method.
- the tablet weight is 340 mg.
- a histidine and vitamin B6-containing solution having the following combination is produced by a conventional method.
- the solution weight is 30 g.
- Histidine and vitamin B6-containing granules having the following combination are produced by a conventional method.
- the volume is 2 g.
- a histidine and vitamin B6-containing jelly having the following combination is produced by a conventional method.
- the weight is 100 g.
- test subjects ingested capsules containing 1.65 g of L-histidine as a daily ingestion amount (5 capsules (hard capsule #2 WHITE OP B/C) containing 0.33 g of L-histidine alone), or control sample capsules (5 capsules containing equal volume of cellulose) for 14 days. After the completion of 14 day ingestion, a 14 day resting period was taken. After the resting period, they ingested the capsules not ingested before the resting period.
- test subjects answered POMS and the VAS questionnaires (fatigue, depression, vague sense, drowsiness, clear thinking, motivation, attentiveness, concentration) relating to fatigue, and cognitive function measurement task CogHealth (under higher difficulty conditions by simultaneously including mental arithmetic task as well) to measure intellectual performance which is one of the fatigue indices. Furthermore, they answered VAS questionnaires after completion of CogHealth. Evaluation after completion of CogHealth reveals the differency of the state between after and before the work-load.
- FIGS. 9B to 9E The results are shown in FIGS. 9B to 9E .
- the fatigue factor scores of POMS significantly decreased (paired t-test: p ⁇ 0.05) ( FIG. 9B ) and the sense of clear thinking, motivation, and attentiveness significantly increased (paired t-test: p ⁇ 0.05) in VAS questionnaires relating to fatigue ( FIG. 9C ) in the test subjects who ingested histidine for 14 days.
- ingestion of histidine shortened the reaction time of cognitive function measurement task and significantly decreased the reaction time of delayed recall task (paired t-test: p ⁇ 0.05) as compared to ingestion of the control food ( FIG. 9D ).
- test subjects took the same meals for 3 days before the experiment, fasted for 10 to for 14 hr, and ingested capsules containing 1.65 g of L-histidine as a single ingestion amount (5 capsules (hard capsule #2 WHITE OP B/C) containing 0.33 g of L-histidine alone), or control sample capsules (5 capsules containing equal volume of cellulose).
- the test subjects answered the VAS questionnaires (fatigue, depression, vague sense, drowsiness, clear thinking, motivation, attentiveness, concentration) relating to fatigue, and cognitive function measurement task CogHealth (under higher difficulty conditions by simultaneously including mental arithmetic task as well) to measure intellectual performance which is one of the fatigue indices. Furthermore, they answered VAS questionnaires after completion of CogHealth. Evaluation after completion of CogHealth reveals the defferency of the state between after and before the work-load.
- VAS questionnaires fatigue, depression, vague sense, drowsiness, clear thinking, motivation, attentiveness, concentration
- FIGS. 10B and 10C The results are shown in FIGS. 10B and 10C . It was found that the work time in 5 kinds of brain function measurement indices was shortened in the test subjects who ingested histidine, as compared to the test subjects who ingested the control food.
- VAS questionnaires relating to fatigue the sense of clear thinking and attentiveness significantly increased and the sense of concentration tended to increase (paired t-test: p ⁇ 0.05) ( FIG. 10B ).
- VAS questionnaires after completion of CogHealth moreover, the sense of vague sense significantly decreased, the sense of depression tended to decrease, and the sense of concentration tended to increase (paired t-test: p ⁇ 0.05) ( FIG. 10C ). This means that ingestion of histidine may be able to suppress vague sense and the sense of depression due to burden and maintain concentration, even when cognitive work is loaded.
- Fatigue (mental fatigue, physical fatigue) can be improved by ingesting the composition of the present invention comprising (1) histidine and (2) vitamin B6 and/or carnosine. Since the active ingredients thereof are amino acid (peptide) and vitamin, the present invention has less fear of causing side effects, is superior in safety, and can be consecutively used every day.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physiology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Non-Alcoholic Beverages (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Compositions and foods which contain (1) histidine and (2) vitamin B6 and/or carnosine are useful for treating, improving, and recovering from fatigue.
Description
- This application is a continuation of International Patent Application No. PCT/JP2014/076989, filed on Oct. 8, 2014, and claims priority to Japanese Patent Application No. 2013-212329, filed on Oct. 9, 2013, both of which are incorporated herein by reference in their entireties.
- The present invention relates to anti-fatigue compositions, foods which contain such a composition, and uses of such a composition.
- Histidine is one kind of basic amino acid, and is an essential amino acid having an imidazoyl group as a heteroaromatic ring in the side chain. Histidine is an amino acid admitted as a food additive, and contained in many foods. For example, histidine is added as a seasoning or flavor-adjusting agent aiming at firm taste, prevention of diffusion of flavor, and the like, and the content thereof is about 50 mg/100 ml at maximum. In relation to the known function of histidine, an anti-fatigue composition containing histidine or histidine hydrochloride is known (see JP-A-2006-137706, which is incorporated herein by reference in its entirety).
- Vitamin B6 is one kind of water-soluble vitamin and is a pyridine derivative. Vitamin B6 includes pyridoxine, pyridoxal and pyridoxamine, and they are mutually convertible. They are phosphorylated in the body into pyridoxal 5′-phosphate (PLP) and
pyridoxamine 5′-phosphoate, and function as a coenzyme of an enzyme involved in amino acid metabolism such as transamination reaction, decarboxylation reaction and the like. They are also necessary for a reaction to biosynthesize niacin from tryptophan as amino acid, a reaction to biosynthesize glucose 1-phosphate from glycogen, and a reaction to synthesize dopamine and y-aminobutyric acid as neurotransmitters. - In 2010, vitamin B6 was determined to have the following functions in the “functional claims for food and supplement” issued by EFSA (European Food Safety Authority) (see EFSA Journal 2010; 8(10):1759, which is incorporated herein by reference in its entirety). Normal homocysteine metabolism, maintenance of normal bones/tooth/hair/skin/nail, normal energy-yielding and metabolism, normal psychological function, reduction of tiredness and fatigue, normal cysteine synthesis.
- Carnosine is a dipeptide wherein histidine and β alanine are bonded, and is contained in animal-derived foods in large amounts. Carnosine is mainly present in muscles and brain, and a buffering action, an antioxidation action and the like are known (see Amino san no kagaku to saishin ouyou gijiyutsu p. 272-282 CMC Publishing Co., Ltd. 2008, which is incorporated herein by reference in its entirety). It has also been reported that imidazole dipeptide which is a mixture of carnosine and anserine (dipeptide wherein 1 methylhistidine and β alanine are bonded) shows an anti-fatigue effect (see Journal of Clinical and Experimental Medicine, vol. 228, No. 6, p. 722-726, 2009, which is incorporated herein by reference in its entirety).
- However, there remains a need for improved anti-fatigue compositions.
- Accordingly, it is one object of the present invention to provide novel anti-fatigue compositions.
- It is another object of the present invention to provide novel foods which contain such an anti-fatigue composition.
- It is another object of the present invention to provide novel methods of treating and/or preventing fatigue.
- When amino acid is added to a food and the like, an influence of the distinct taste of amino acid needs to be considered in some occasions. While histidine is known to have an anti-fatigue effect, since histidine also has a sour taste and a bitter taste, the amount thereof to be added to foods tends to be limited, which sometimes prevents exhibition of a sufficient anti-fatigue action. Therefore, the present invention aims to provide a histidine-containing food capable of affording a sufficient anti-fatigue effect even at a low histidine content, and the like.
- These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors' discovery that fatigue can be more effectively improved by using histidine in combination with vitamin B6 and/or carnosine, particularly that a fatigue-improving effect can be obtained even at a low dose at which a single use of each of them cannot provide an effect. Thus, the present invention provides:
- (1) An anti-fatigue composition, comprising (1) histidine and (2) vitamin B6 and/or carnosine in combination.
- (1-1) A method of improving fatigue, comprising administering (1) an effective amount of histidine and (2) an effective amount of vitamin B6 and/or carnosine to a subject in need thereof.
- (1-2) A composition for improving fatigue, comprising (1) histidine and (2) vitamin B6 and/or carnosine in combination.
- (2) The composition of the above-mentioned (1), comprising histidine and vitamin B6 in combination.
- (2-1) A method of improving fatigue, comprising administering an effective amount of histidine and an effective amount of vitamin B6 to a subject in need thereof.
- (2-2) A composition for improving fatigue, comprising histidine and vitamin B6 in combination.
- (3) The composition of the above-mentioned (1), comprising histidine and carnosine in combination.
- (3-1) A method of improving fatigue, comprising administering an effective amount of histidine and an effective amount of carnosine to a subject in need thereof.
- (3-2) A composition for improving fatigue, comprising histidine and carnosine in combination.
- (4) The composition of the above-mentioned (2), wherein the histidine:vitamin B6 is 5:3-350:1.
- (4-1) The method of the above-mentioned (2-1), wherein the histidine:vitamin B6 is 5:3 to 350:1.
- (4-2) The composition of the above-mentioned (2-2), wherein the histidine:vitamin B6 is 5:3 to 350:1.
- (5) The composition of the above-mentioned (4), wherein the histidine is contained at not less than 0.3 g per unit package.
- (5-2) The composition of the above-mentioned (4-2), wherein the histidine is contained at not less than 0.3 g per unit package.
- (6) The composition of the above-mentioned (4) or (5), wherein the histidine is contained at not less than 0.3 g as an ingestion amount per meal.
- (6-2) The composition of the above-mentioned (4-2) or (5-2), wherein the histidine is contained at not less than 0.3 g as an ingestion amount per meal.
- (7) The composition of any of the above-mentioned (4)-(6), wherein the vitamin B6 is contained at not less than 0.5 mg as an ingestion amount per meal.
- (7-2) The composition of any of the above-mentioned (4-2), (5-2) and (6-2), wherein the vitamin B6 is contained at not less than 0.5 mg as an ingestion amount per meal.
- (8) The composition of the above-mentioned (3), wherein histidine:carnosine is 1:4 to 100:1.
- (8-2) The composition of the above-mentioned (3-2), wherein histidine:carnosine is 1:4 to 100:1.
- (9) A container-packed food, comprising (1) histidine and (2) vitamin B6 and/or carnosine.
- (10) The container-packed food of the above-mentioned (9), comprising histidine and vitamin B6.
- (11) The container-packed food of the above-mentioned (9), comprising histidine and carnosine.
- (12) The container-packed food of the above-mentioned (10), wherein histidine:vitamin B6 is 5:3 to 350:1.
- (13) The container-packed food of the above-mentioned (12), wherein the histidine is contained at not less than 0.3 g as an ingestion amount per meal.
- (14) The container-packed food of the above-mentioned (12) or (13), wherein the vitamin B6 is contained at not less than 0.5 mg as an ingestion amount per meal.
- (15) The container-packed food of any of the above-mentioned (9)-(14), further comprising at least one kind of additive selected from excipient, corrigent and flavor.
- (16) The container-packed food of any of the above-mentioned (9)-(15), which is in the form of a solid, semi-solid or liquid.
- (17) The container-packed food of any of the above-mentioned (9)-(15), which is in the form of powder, tablet, granule or capsule.
- (18) The container-packed food of any of the above-mentioned (9)-(15), which is in the form of slurry, solution, jelly or emulsion.
- (19) The container-packed food of any of the above-mentioned (9)-(18), which is in a unit package form per meal.
- (20) The container-packed food of any of the above-mentioned (9)-(19), which is for improving fatigue.
- (21) A food comprising (1) histidine and (2) vitamin B6 and/or carnosine, which is in a unit package form per meal.
- (22) The food of the above-mentioned (21) comprising histidine and vitamin B6, which is in a unit package form per meal.
- (23) The food of the above-mentioned (21) comprising histidine and carnosine, which is in a unit package form per meal.
- (24) The food of the above-mentioned (22), wherein histidine:vitamin B6 is 5:3 to 350:1.
- (25) The food of the above-mentioned (24), wherein histidine is contained at not less than 0.3 g.
- (26) The food of the above-mentioned (24) or (25), wherein vitamin B6 is contained at not less than 0.5 mg. (27) The food of the above-mentioned (23), wherein histidine:carnosine is 1:4 to 100:1.
- (28) The food of the above-mentioned (27), wherein histidine is contained at not less than 0.3 g.
- (29) The food of any of the above-mentioned (21)-(28), further comprising at least one kind of additive selected from excipient, corrigent and flavor.
- (30) The food of any of the above-mentioned (21)-(29), which is in the form of a solid, semi-solid or liquid.
- (31) The food of any of the above-mentioned (21)-(29), which is in the form of powder, tablet, granule or capsule.
- (32) The food of any of the above-mentioned (21)-(29), which is in the form of slurry, solution, jelly or emulsion.
- (33) The food of any of the above-mentioned (21)-(32), which is a food with health claims.
- (34) The food of any of the above-mentioned (21)-(33), which is for improving fatigue.
- (35) A container-packed drink comprising (1) histidine and (2) vitamin B6 and/or carnosine.
- (36) The container-packed drink of the above-mentioned (35), comprising histidine and vitamin B6.
- (37) The container-packed drink of the above-mentioned (35), comprising histidine and carnosine.
- (38) The container-packed drink of the above-mentioned (36), wherein histidine:vitamin B6 is 5:3 to 350:1.
- (39) The container-packed drink of the above-mentioned (38), wherein histidine is contained at not less than 0.3 g as an ingestion amount per meal.
- (40) The container-packed drink of the above-mentioned (38), wherein histidine is contained at not less than 1 w/v%.
- (41) The container-packed drink of any of the above-mentioned (38)-(40), wherein vitamin B6 is contained at not less than 0.5 mg as an ingestion amount per meal.
- (42) The container-packed drink of any of the above-mentioned (35)-(41), which is in a unit package form per meal.
- (43) The container-packed drink of any of the above-mentioned (35)-(42), which is a food with health claims.
- (44) The container-packed drink of any of the above-mentioned (35)-(43), which is for improving fatigue.
- Fatigue (mental fatigue, physical fatigue) can be improved by ingesting the composition of the present invention, comprising (1) histidine and (2) vitamin B6 and/or carnosine. Since the present invention contains amino acid (peptide) and vitamin as active ingredients, it has less fear of causing side effects and is superior in safety, and can also be consecutively used everyday.
- A more complete appreciation of the invention and many of the attendant advantages thereof will be readily obtained as the same become better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein:
-
FIG 1A shows the protocol of generating a fatigue model by burden of insufficient sleep, for the measurement of locomotor activities in the dark phase. -
FIG. 1B shows cumulative locomotor activities for the former half (6 hr) of the dark phase. *: t-test, p<0.05. -
FIG. 2A shows the protocol for generating a fatigue model by burden of insufficient sleep, for the measurement of short-working memory. -
FIG. 2B shows the measurement results of alternation behavior. ***: t-test, p<0.001. -
FIG. 3A shows the protocol for verifying the effect of the ingestion of histidine (His) and/or test substance X on the improvement of a decrease in the locomotor activities in the dark phase (fatigue index) of mouse after burden of insufficient sleep. -
FIG. 3B shows cumulative locomotor activities for the former half (6 hr) of the dark phase when histidine (His) and/or vitamin B6 (VB6) are used. *: Tukey's multiple test, p<0.05. †t: Tukey's multiple test, p<0.1. -
FIG. 3C shows cumulative locomotor activities for the former half (6 hr) of the dark phase when histidine (His) and/or carnosine are used. *: Tukey's multiple test, p<0.05. -
FIG. 4A shows the protocol for verifying the effect of the ingestion of histidine (His) and/or vitamin B6 (VB6) on the change of short-working memory (fatigue index) of mouse after burden of insufficient sleep. -
FIG. 4B shows the measurement results of alternation behavior. **: Tukey's multiple test, p<0.01. *: Tukey's multiple test, p<0.05. -
FIG. 5A shows the protocol for verifying the effect of the ingestion of histidine (His) and/or vitamin B6 (VB6) (His:VB6=120:1) on the change of short-working memory (fatigue index) of mouse after burden of insufficient sleep. -
FIG. 5B shows the measurement results of alternation behavior. **: Tukey's multiple test, p<0.01. *: Tukey's multiple test, p<0.05. -
FIG. 6A shows the protocol for verifying the effect of the ingestion of histidine (His) and/or vitamin B6 (VB6) (His:VB6=120:1) on the change of locomotor activities (fatigue index) of mouse after burden of insufficient sleep. -
FIG. 6B shows the measurement results of locomotor activities in the dark phase. *: Tukey's multiple test, p<0.05 vs VB6 group. #: Tukey's multiple test, p<0.05 vs solvent group. †t: Tukey's multiple test, p<0.1 vs solvent group. ‡: Tukey's multiple test, p<0.1 vs His group. §: Tukey's multiple test, p<0.1 vs VB6 group. -
FIG. 6C shows the measurement results of locomotor activities in 4 hr to 5 hr after the start of the dark phase. #: Tukey's multiple test, p<0.05 vs solvent group. ‡: Tukey's multiple test, p<0.1 vs His group. §: Tukey's multiple test, p<0.1 vs VB6 group. -
FIG. 7A shows the protocol for verifying the effect of the ingestion of histidine (His) and/or vitamin B6 (VB6) (His:VB6=360:1) on the change of short-working memory (fatigue index) of mouse after burden of insufficient sleep. -
FIG. 7B shows the measurement results of alternation behavior. *: Tukey's multiple test, p<0.05. -
FIG. 8A shows the protocol for verifying the effect of the ingestion of histidine (His) and/or vitamin B6 (VB6) (His:VB6=360:1) on the change of locomotor activities (fatigue index) of mouse after burden of insufficient sleep. -
FIG. 8B shows the measurement results of locomotor activities in the dark phase. -
FIG. 9A shows the protocol for verifying the anti-fatigue effect of histidine (His) ingestion in test subjects feeling fatigue and a decrease in the quality of sleep. -
FIG. 9B shows variation of T scores in POMS. *: paired t-test, p<0.05. -
FIG. 9C shows variation of each index in VAS before cognitive functioning test (CogHealth). *: paired t-test, p<0.05. -
FIG. 9D shows variation in the reaction time in cognitive functioning test. *: paired t-test, p<0.05. -
FIG. 9E shows variation of each index in VAS after cognitive functioning test. *: paired t-test, p<0.05. -
FIG. 10A shows the protocol for verifying the anti-fatigue effect of single histidine (His) ingestion in test subjects feeling fatigue and a decrease in the quality of sleep. -
FIG. 10B shows variation of each index in VAS before cognitive functioning test (CogHealth). *: paired t-test, p<0.05. -
FIG. 10C shows variation of each index in VAS after cognitive functioning test. *: paired t-test, p<0.05. -
FIG. 11A shows the protocol for verifying the effect of the ingestion of histidine (His) and/or vitamin B6 (VB6) (His:VB6=300:1) on the change of short-working memory (fatigue index) of mouse after burden of insufficient sleep. -
FIG. 11B shows the measurement results of alternation behavior. *: Tukey's multiple test, p<0.05. - The mode of embodiment of the present invention is explained below.
- In the present invention, histidine is an essential amino acid having the following structural formula.
- The histidine used in the present invention may be a substance convertible to histidine by hydrolysis. The “substance convertible to histidine by hydrolysis” is a substance that affords histidine by hydrolysis (particularly in vivo hydrolysis), and typical examples thereof include proteins and peptides containing histidine as a constituent unit. A substance that affords histidine by hydrolysis produces histidine by hydrolysis in the body after ingestion, and is expected to provide an effect similar to that obtained when histidine is ingested from the start.
- The histidine to be used in the present invention may be one extracted and purified from naturally-present animals, plants and the like, or one obtained by a chemical synthesis method, a fermentation method, an enzyme method or a gene recombination method. Any of L-form, D-form, and DL-form can be used. A commercially available one can be utilized and is preferable since it is convenient.
- Vitamin B6 is one kind of water-soluble vitamin having the following structure.
- Vitamin B6 includes pyridoxine, pyridoxal, and pyridoxamine, which are mutually convertible. While the vitamin B6 used in the present invention may be any compound as long as a desired effect can be exhibited, it is preferably pyridoxine.
- The vitamin B6 to be used in the present invention may be one extracted and purified from naturally-present animals, plants and the like, or one obtained by a chemical synthesis method. A commercially available one can be utilized and is preferable since it is convenient.
- Carnosine is a dipeptide having the following structure, wherein histidine and β alanine are bonded.
- The carnosine to be used in the present invention may be one extracted and purified from naturally-present animals, plants and the like, or one obtained by a chemical synthesis method, a fermentation method, an enzyme method or a gene recombination method. While L-form and D-form (naturally L-form alone) are present due to stereoisomerism, any of them can be used. A commercially available one can be utilized and is preferable since it is convenient.
- The carnosine used in the present invention may be a substance convertible to carnosine by hydrolysis. The “substance convertible to carnosine by hydrolysis” is a substance that affords carnosine by hydrolysis (particularly in vivo hydrolysis), and typical examples thereof include proteins and peptides containing carnosine as a constituent unit. A substance that affords carnosine by hydrolysis produces carnosine by hydrolysis in the body after ingestion, and is expected to provide an effect similar to that obtained when carnosine is ingested from the start.
- In the present specification, when histidine per se is used as the histidine, the content of histidine in a composition or food is determined taking note of the weight of histidine and, when a substance convertible to histidine by hydrolysis is used, by converting to histidine. When a composition or food contains both histidine and a substance convertible to histidine by hydrolysis, the content of histidine in the composition or food is the total weight of the weight of histidine obtained by converting, by hydrolysis, all substances convertible to histidine by hydrolysis, and histidine presented from the start.
- Similarly, when carnosine per se is used as the carnosine, the content of carnosine in a composition or food is determined taking note of the weight of carnosine and, when a substance convertible to carnosine by hydrolysis is used, by converting to carnosine. When a composition or food contains both carnosine and a substance convertible to carnosine by hydrolysis, the content of carnosine in the composition or food is the total weight of the weight of carnosine obtained by converting, by hydrolysis, all substances convertible to carnosine by hydrolysis, and carnosine presented from the start.
- Histidine (or substance convertible to histidine by hydrolysis), vitamin B6, and carnosine (or substance convertible to carnosine by hydrolysis) used in the present invention may be in the form of a salt. The form of the salt may be, for example, acid addition salt, salt with a base and the like, and pharmacologically acceptable salt is preferable. Examples of such salt include salts with inorganic acids, salts with organic acids, salts with inorganic bases, and salts with organic bases.
- Examples of the salt with an inorganic acid include salts with hydrohalic acid (hydrochloric acid, hydrobromic acid, hydroiodic acid etc.), sulfuric acid, nitric acid, phosphoric acid, and the like.
- Examples of the salt with an organic acid include salts with formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, maleic acid, fumaric acid, citric acid, and the like.
- Examples of the salt with an inorganic base include salts with alkali metals such as sodium, potassium, lithium and the like, salts with alkaline earth metals such as calcium, magnesium and the like, salt with ammonium and the like.
- Examples of the salt with an organic base include salts with ethylenediamine, propylenediamine, ethanolamine, monoalkylethanolamine, dialkylethanolamine, diethanolamine, triethanolamine and the like.
- In the present specification, histidine, “substance convertible to histidine by hydrolysis” and a salt thereof are hereinafter generically referred to as histidine, and carnosine, “substance convertible to carnosine by hydrolysis” and a salt thereof are hereinafter generically referred to as carnosine.
- One embodiment of the present invention is an anti-fatigue composition containing (1) histidine and (2) vitamin B6/or carnosine in combination and, particularly, an anti-fatigue composition containing histidine and vitamin B6 in combination, and an anti-fatigue composition containing histidine and carnosine in combination are provided.
- Another embodiment of the present invention is a method of improving fatigue, comprising administering (1) an effective amount of histidine, and (2) vitamin B6 and/or an effective amount of carnosine to a subject in need thereof and, particularly, a method of improving fatigue, comprising administering (1) an effective amount of histidine and (2) an effective amount of vitamin B6 to a subject in need thereof, and a method of improving fatigue, comprising administering (1) an effective amount of histidine, and (2) an effective amount of carnosine to a subject in need thereof are provided.
- Another embodiment of the present invention is a composition containing (1) histidine and (2) vitamin B6 and/or carnosine in combination for improving fatigue and, particularly, a composition containing histidine and vitamin B6 in combination for improving fatigue, and a composition containing histidine and carnosine in combination for improving fatigue are provided.
- The anti-fatigue composition, the method of improving fatigue, and the composition for improving fatigue of the present invention may use histidine in combination with vitamin B6, histidine in combination with carnosine, or histidine in combination with vitamin B6 and carnosine. Preferably, they use histidine in combination with vitamin B6. The combination ratio of histidine and vitamin B6 can be appropriately determined within the range where an anti-fatigue effect can be obtained.
- Preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 15:1 to 350:1, 30:1 to 350:1, 60:1 to 350:1, and 90:1 to 350:1. Other preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 5:3 to 300:1, 5:3 to 240:1, and 5:3 to 120:1. Still other preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 15:1 to 300:1, 30:1 to 240:1, 60:1 to 120:1, and 90:1 to 120:1.
- The combination ratio of histidine and carnosine can also be determined appropriately within the range where an anti-fatigue effect can be obtained.
- Preferable combination ratios include histidine:carnosine =1:4 to 100:1, 1:2 to 100:1, and 1:1 to 100:1. Other preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:4 to 50:1, and 1:4 to 30:1. Other preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:2 to 50:1, and 1:1 to 30:1.
- When both vitamin B6 and carnosine are administered for combined use with histidine, the dose of vitamin B6 and/or carnosine can be reduced as compared to a single administration thereof.
- In the composition of the present invention, the administration form of (1) histidine and (2) vitamin B6/or carnosine is not particularly limited, and (1) and (2) only need to be combined at the time of administration. Examples of such administration form include:
- (A) administration as a single composition simultaneously containing (1) and (2),
- (B) simultaneous administration of two kinds (or 3 kinds) of compositions separately containing (1) and (2) by the same administration route,
- (C) administration of two kinds (or 3 kinds) of compositions separately containing (1) and (2) by the same administration route in a staggered manner,
- (D) simultaneous administration of two kinds (or 3 kinds) of compositions separately containing (1) and (2) by different administration routes,
- (E) administration of two kinds (or 3 kinds) of compositions separately containing (1) and (2) by different administration routes in a staggered manner and the like.
- In 2010, the Japanese Society of Fatigue Science reported the definition of “fatigue” as “fatigue is decline in the ability for activity of the body accompanied by a peculiar sense of discomfort and a desire to rest, caused by excessive mental and psychological activities, or disease(s)”.
- That is, “fatigue” is defined to be reduction of performance. In the present invention, “fatigue” is intended to mean both mental fatigue and physical fatigue. The term “anti-fatigue” or “fatigue improvement” refers to a fatigue recovery action that promptly recovers the body from the state of fatigue, effect of relieving fatigue when physical burden and mental burden (including burden of insufficient sleep and the like) are applied, or an action to relieve stresses felt daily such as copiopia, mental fatigue, or mental insufficiency and the like, and further, improve efficiency of brain work.
- The anti-fatigue composition of the present invention refers to a composition that improves or recovers decline in the ability for activity of the body accompanied by a peculiar sense of discomfort and a desire to rest, caused by excessive mental and psychological activities, or a disease.
- The anti-fatigue effect can be evaluated by a method known per se. Examples of such methods include subjective evaluation methods such as visual analog scale (VAS), Profile of Mood States (POMS) and the like, and objective evaluation methods such as cognitive functioning test .Coghealth (Coghealth: manufactured by Cogstate Ltd., Health Solution, Inc. provide) capable of measuring a brain function which will be decreased due to fatigue and aging.
- When VAS is utilized, for example, the level of fatigue can be judged by evaluating whether the test subject shows low scores of positive index (clear thinking, motivation, attentiveness or concentration), or high score of negative index (depression or drowsiness). When, for example, scores are measured before and after continuous ingestion or single ingestion of a test sample for a given period, and the score of positive index significantly increases or the score of negative index significantly decreases after sample ingestion, the fatigue can be evaluated to have been improved. Particularly, one or more indices selected from the group consisting of clear thinking, motivation, attentiveness, concentration, depression and drowsinesscan can be significantly improved by ingesting the composition of the present invention.
- When POMS is utilized, for example, the level of fatigue can be judged by evaluating whether the test subject shows low scores of positive index (vigor), or high score of negative index (anxiety, depression, anger, fatigue or confusion). More specifically, when the score of fatigue factor (F factor) is not less than 16 by subjective evaluation by POMS, the presence of fatigue is admitted. When, for example, scores are measured before and after continuous ingestion or single ingestion of a test sample for a given period, and the score of positive index significantly increases or the score of negative index significantly decreases after sample ingestion, the fatigue can be evaluated to have been improved. Particularly, the indices of fatigue and confusion can be significantly improved by ingesting the composition of the present invention.
- When CogHealth is utilized, for example, the level of fatigue can be judged by evaluating whether the accuracy rate is low or the reaction time is long in a simple reaction or delayed recall. Furthermore, for example, when a test is performed after continuous ingestion of a test sample or placebo for a given period, and the accuracy rate significantly increases or the reaction time significantly decreases in a test sample ingestion group in a simple reaction or delayed recall as compared to placebo ingestion group, the fatigue can be evaluated to have been improved by ingesting the test sample. Particularly, the reaction time in the delayed recall can be significantly lowered by ingesting the composition of the present invention.
- For evaluation of fatigue and anti-fatigue in animals, a decrease in performance and recovery of the decrease (change in locomotor activities, alternation behavior showing short-working memory in the below-mentioned Y-maze test etc. as indices) only need to be measured by a method known per se, after applying a physical burden (treadmill, swimming etc.), mental burden (restraint stress etc.), or composite stress burden including both (insufficient sleep in water bed etc.). For example, a data acquisition analysis system containing an infrared sensor (e.g., NS-DAS-32 (NeuroScience, Inc) and the like) can be utilized. For example, measurement is performed after continuous ingestion of a test sample or a control sample for a given period by a target with fatigue induced by various burdens and, when a decrease in the performance (decrease in spontaneous amount and alternation behavior) is improved in a is test sample ingestion group as compared to a control sample ingestion group, the fatigue can be evaluated to have been improved/recovered by the ingestion of the test sample.
- The anti-fatigue composition of the present invention may be solid or semi-solid, or liquid such as powder, tablet, granule, capsule, slurry, solution, jelly, emulsion, and the like.
- As one embodiment of the anti-fatigue composition of the present invention, a composition containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, as an ingestion amount per meal is provided. From the aspects of eating experiences obtained from known findings (Food Safety Commission of Japan, Feed/Fertilizer, etc. Expert Committee, April 2010, exempted evaluation report histidine, safety and effectiveness information of “health food” (National Institute of Health and Nutrition HP https://hfnet.nih.go.jp/) which is incorporated herein by reference in its entirety) and easiness of packaging and ingestion, the ingestion amount per meal of histidine is preferably not more than 23 g, more preferably not more than 4 g. In the present invention, since the effect of combined use of vitamin B6 on the anti-fatigue effect can be expected, the ingestion amount per meal of histidine can be further reduced and, for example, an anti-fatigue composition containing not more than 3 g, preferably not more than 2 g, of histidine as an ingestion amount per meal can be provided.
- In one embodiment of the anti-fatigue composition of the present invention, a composition containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, per unit package is provided. Specifically, an anti-fatigue composition packaged as an ingestion amount per meal as one unit is provided.
- In another embodiment of the anti-fatigue composition of the present invention, a composition containing histidine:vitamin B6 at the above-mentioned combination ratio, and vitamin B6 at not less than 0.5 mg, preferably not less than 2 mg, more preferably not less than 4 mg, further preferably not less than 6 mg, further preferably not less than 8 mg, further preferably not less than 10 mg, further preferably not less than 15 mg, is provided. The ingestion amount of vitamin B6 per meal is generally less than 300 mg, preferably not more than 100 mg, since ingestion of an amount exceeding this level does not remarkably enhance the anti-fatigue effect.
- The anti-fatigue composition of the present invention can be provided as a food. In the present specification, food is a concept widely encompassing oral ingestible matters, and includes not only what is called “food” but also a drink, health aid food, food with health claims, supplement, and the like. In the present invention, an anti-fatigue composition provided as food, food such as food in a unit package form per meal and the like, container-packed food, and container-packed drink are sometimes to be generically referred to as the food of the present invention. In addition, the anti-fatigue composition of the present invention can be provided as an agent. In the present specification, the agent excludes pharmaceutical products, and is ingested for a particular purpose, different from those daily ingested to retain nutrition of the body.
- The form of the food of the present invention is not particularly limited, and may be solid or semi-solid, or liquid m such as powder, tablet, granule, slurry, capsule, solution, jelly, emulsion, and the like.
- The form of histidine, and vitamin B6 and/or carnosine to be contained in the food of the present invention is not particularly limited, and may be powder or granule, slurry, tablet confectionery, capsule, solution, jelly, or emulsion. Of these, granule and powder are preferable, in view of easy portability and easy packaging. In addition, solution, jelly, and slurry are also preferable in view of easy ingestion.
- In the present invention, examples of the unit package form per meal include a form that defines a given amount in a pack, package, bottle, etc. in the case of drink, confectionery, jelly, pudding, yogurt, and the like, and package and the like can define a given amount in the case of granular, powdery and slurry foods. Alternatively, a form such as a container and the like indicating the ingestion amount per meal can be mentioned. As used herein, confectionery refers to favorite foods such as sweet stuff and the like, which are eaten other than meals, and examples thereof include candy, chewing gum, tablet confectionery, chocolate, shake, ice, and the like.
- The present invention provides a food comprising (1) histidine and (2) vitamin B6/or carnosine, which is in a unit package form per meal, particularly, a food comprising histidine and vitamin B6, which is in a unit package form per meal, and a food comprising histidine and carnosine, which is in a unit package form per meal.
- The food in a unit package form per meal of the present invention may contain histidine and vitamin B6, or histidine and carnosine, or histidine and vitamin B6, and carnosine. Preferred is one containing histidine and vitamin B6.
- The combination ratio of histidine and vitamin B6 can be appropriately determined within the range where an anti-fatigue effect can be obtained.
- Preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 15:1 to 350:1, 30:1 to 350:1, 60:1 to 350:1, and 90:1 to 350:1. Other preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 5:3 to 300:1, 5:3 to 240:1, and 5:3 to 120:1. Still other preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 15:1 to 300:1, 30:1 to 240:1, 60:1 to 120:1, and 90:1 to 120:1.
- The combination ratio of histidine and carnosine can also be determined appropriately within the range where an anti-fatigue effect can be obtained.
- Preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:2 to 100:1, and 1:1 to 100:1. Other 20 preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:4 to 50:1, and 1:4 to 30:1. Other preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:2 to 50:1, and 1:1 to 30:1.
- When both vitamin B6 and carnosine are contained in addition to histidine, the content of vitamin B6 and/or carnosine can be reduced as compared to a single administration thereof.
- As one embodiment of the food in a unit package form per meal of the present invention, a composition containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, as an ingestion amount per meal is provided. From the aspects of eating experiences obtained from known finding (mentioned above) and easiness of packaging and ingestion, the ingestion amount per meal of histidine is preferably not more than 23 g, more preferably not more than 4 g. In the present invention, since the effect of combined use of vitamin B6 on the anti-fatigue effect can be expected, the ingestion amount per meal of histidine can be further reduced and, for example, a food containing not more than 3 g, preferably not more than 2 g, of histidine as an ingestion amount per meal can be provided.
- In one embodiment of the food in a unit package form per io meal of the present invention, a food containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, per unit package is provided.
- In another embodiment of the food in a unit package form per meal of the present invention, a food containing histidine:vitamin B6 at the above-mentioned combination ratio, and vitamin B6 at not less than 0.5 mg, preferably not less than 2 mg, more preferably not less than 4 mg, further preferably not less than 6 mg, further preferably not less than 8 mg, further preferably not less than 10 mg, further preferably not less than 15 mg, is provided. The ingestion amount of vitamin B6 per meal is generally less than 300 mg, preferably not more than 100 mg, since ingestion of an amount exceeding this level does not remarkably enhance the anti-fatigue effect.
- Another embodiment of the present invention is a container-packed food, comprising (1) histidine and (2) vitamin B6 and/or carnosine, particularly a container-packed food comprising histidine and vitamin B6, and a container-packed food comprising histidine and carnosine. The “food” in the container-packed food of the present invention is, for example, the above-mentioned anti-fatigue composition provided as food. It can be produced by injecting or filling the food in a desired container.
- The container-packed food of the present invention may contain histidine and vitamin B6, or histidine and carnosine, or histidine and vitamin B6 and carnosine. Preferred is one containing histidine and vitamin B6. The combination ratio of histidine and vitamin B6 in the food can be appropriately determined within the range where an anti-fatigue effect can be obtained.
- Preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 15:1 to 350:1, 30:1 to 350:1, 60:1 to 350:1, and 90:1 to 350:1. Other preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 5:3 to 300:1, 5:3 to 240:1, and 5:3 to 120:1. Still other preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 15:1 to 300:1, 30:1 to 240:1, 60:1 to 120:1, and 90:1 to 120:1.
- The combination ratio of histidine and carnosine can also be determined appropriately within the range where an anti-fatigue effect can be obtained.
- Preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:2 to 100:1, and 1:1 to 100:1. Other preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:4 to 50:1, and 1:4 to 30:1. Other preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:2 to 50:1, and 1:1 to 30:1.
- As one embodiment of the container-packed food of the present invention, a container-packed food containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, as an ingestion amount per meal is provided. From the aspects of eating experiences obtained from known finding (mentioned above) and easiness of packaging and ingestion, the ingestion amount per meal of histidine is preferably not more than 23 g, more preferably not more than 4 g. In the present invention, since the effect of combined use of vitamin B6 on the anti-fatigue effect can be expected, the ingestion amount per meal of histidine can be further reduced and, for example, a container-packed food containing not more than 3 g, preferably not more than 2 g, of histidine as an ingestion amount per meal can be provided.
- In another embodiment of the container-packed food of the present invention, a container-packed food containing histidine:vitamin B6 at the above-mentioned combination ratio, and vitamin B6 at not less than 0.5 mg, preferably not less than 2 mg, more preferably not less than 4 mg, further preferably not less than 6 mg, further preferably not less than 8 mg, further preferably not less than 10 mg, further preferably not less than 15 mg, is provided. The ingestion amount of vitamin B6 per meal is generally less than 300 mg, preferably not more than 100 mg, since ingestion of an amount exceeding this level does not remarkably enhance the anti-fatigue effect.
- Another embodiment of the present invention is a container-packed drink, comprising (1) histidine and (2) vitamin B6 and/or carnosine, particularly a container-packed drink comprising histidine and vitamin B6, and a container-packed drink comprising histidine and carnosine. The container-packed drink of the present invention is one embodiment of the above-mentioned container-packed food of the present invention. The “drink” in the container-packed drink of the present invention includes, for example, the above-mentioned anti-fatigue composition provided as a drink, specifically, drinks such as tea drinks (e.g., green tea, oolong tea, black tea, etc.), alcohol drinks (e.g., beer, wine, sake, distilled spirits, ume (Japanese plum) wine, low-malt beer, whiskey, brandy, etc.), beverage (e.g., sports drinks, isotonic drinks, mineral water, coffee drinks, etc.), juice (e.g., fruit juice, vegetable juice, etc.) and the like, liquid seasoning (e.g., soy sauce, vinegar, liquor, sweet sake for seasoning, soup stock, etc.), liquid supplement (e.g., nutritional supplement drink, beauty drink, energy drink, etc.), and the like. It can be produced by injecting or filling the drink in a desired container. The drink includes not only those served as a solution, a suspension and the like, but also those served for drinking after extraction and dissolution such as tea leaves, coffee beans, powder drinks, and the like.
- The container-packed drink of the present invention may contain histidine and vitamin B6, or histidine and carnosine, or histidine and vitamin B6 and carnosine. Preferred is one containing histidine and vitamin B6. The combination ratio of histidine and vitamin B6 in the drink can be appropriately determined within the range where an anti-fatigue effect can be obtained. Preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 15:1 to 350:1, 30:1 to 350:1, 60:1 to 350:1, and 90:1 to 350:1. Other preferable 15 combination ratios include histidine:vitamin B6=5:3 to 350:1, 5:3 to 300:1, 5:3 to 240:1, and 5:3 to 120:1. Still other preferable combination ratios include histidine:vitamin B6=5:3 to 350:1, 15:1 to 300:1, 30:1 to 240:1, 60:1 to 120:1, and 90:1 to 120:1.
- The combination ratio of histidine and carnosine can also be determined appropriately within the range where an anti-fatigue effect can be obtained. Preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:2 to 100:1, and 1:1 to 100:1. Other preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:4 to 50:1,and 1:4 to 30:1. Other preferable combination ratios include histidine:carnosine=1:4 to 100:1, 1:2 to 50:1, and 1:1 to 30:1.
- As one embodiment of the container-packed drink of the present invention, a container-packed drink containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at not less than 0.3 g, preferably not less than 0.5 g, more preferably not less than 0.7 g, further preferably not less than 1 g, as an ingestion amount per meal is provided. From the aspects of eating experiences obtained from known finding (mentioned above) and easiness of packaging and ingestion, the ingestion amount per meal of histidine is preferably not more than 23 g, more preferably not more than 4 g. In the present invention, since the effect of combined use of vitamin B6 on the anti-fatigue effect can be expected, the ingestion amount per meal of histidine can be further reduced and, for example, a container-packed drink containing not more than 3 g, preferably not more than 2 g, of histidine as an ingestion amount per meal can be provided.
- As one embodiment of the container-packed drink of the present invention, a drink containing histidine:vitamin B6 at the above-mentioned combination ratio, and histidine at a concentration of not less than 1 w/v% can be ingested in necessary quantities for necessary times. A container-packed drink preferably at not less than 3 w/v%, more preferably not less than 5 w/v%, is provided. A container-packed drink generally at not more than 30 w/v%, preferably not more than 20 w/v%, more preferably not more than 17 w/v%, further preferably not more than 10 w/v%, is provided.
- In another embodiment of the container-packed drink of the present invention, a container-packed drink containing histidine:vitamin B6 at the above-mentioned combination ratio, and vitamin B6 at not less than 0.5 mg, preferably not less than 2 mg, more preferably not less than 4 m, further preferably not less than 6 mg, further preferably not less than 8 mg, further preferably not less than 10 mg, further preferably not less than 15 mg, is provided. The ingestion amount of vitamin B6 per meal is generally less than 300 mg, preferably not more than 100 mg, since ingestion of an amount exceeding this level does not remarkably enhance the anti-fatigue effect.
- A container to be used for the container-packed food or container-packed drink of the present invention is appropriately selected according to the object. Generally, a can, bottle, PET bottle, paper container, aluminum pouch, and the like can be mentioned. The volume is not particularly limited, and one or more units may be housed in one container wherein ingestion amount per meal is one unit, or concentrated food/drink may be filled in a container.
- The histidine, and vitamin B6 and/or carnosine contained in the food of the present invention being “slurry” means that solid histidine, and vitamin B6 and/or carnosine are suspended in a liquid medium. A part of histidine, and vitamin B6 and/or carnosine may be dissolved in the above-mentioned medium.
- In the food of the present invention, the ingestion form (1) histidine and (2) vitamin B6/or carnosine is not particularly limited, and (1) and (2) only need to be combined at the time of ingestion. Examples of such administration form include
- (A) ingestion as a single food simultaneously containing (1) and (2),
- (B) simultaneous ingestion of two kinds (or 3 kinds) of foods separately containing (1) and (2) by the same administration route,
- (C) ingestion of two kinds (or 3 kinds) of foods separately containing (1) and (2) by the same administration route in a staggered manner,
- (D) simultaneous ingestion of two kinds (or 3 kinds) of foods separately containing (1) and (2) by different administration routes,
- (E) ingestion of two kinds (or 3 kinds) of foods separately containing (1) and (2) by different administration routes in a staggered manner,
- and the like.
- Examples of the application target of the food of the present invention include experiment animals such as rodents (e.g., mouse, rat, hamster, guinea pig, and the like), rabbit and the like, pets such as a dog, cat, and the like, domestic animals and poultry such as bovine, swine, goat, horse, sheep, chicken, and the like, primates such as monkey, orangutan, chimpanzee, and the like, humans, and the like, and human is particularly preferable. For application to an animal other than human, the dose of the food of the present invention can be appropriately moderated based on the general description of the dose for human, which is described in the present specification, and further considering the body weight or size of the animal, or the condition, sensitivity and the like of the administration subject at the time of administration.
- The food of the present invention is preferably food with health claims, more preferably food for improving fatigue.
- The food of the present invention can contain various additives in an attempt to provide the same in a form easier to take. Specifically, a corrigent, flavor, excipient, lubricant, and the like can be mentioned, and any additive can be utilized as long as addition to food is admitted. Examples of the corrigent include souring agents such as ascorbic acid, tartaric acid, citric acid, malic acid and salts of these, and the like, sweeteners such as aspartame, stevia, sucralose, glycyrrhizinic acid, thaumatin, acesulfame potassium, saccharin, saccharin sodium and the like, and the like. Examples of the flavor include synthetic flavor compounds such as L-menthol and the like, citrus essential oils such as orange, lemon, lime, grapefruit, and the like, plant essential oils such as a flower essential oil, peppermint oil, spearmint oil, spice oil, and the like, and the like. Examples of the excipient include lactose, sucrose, D-mannitol, starch, cornstarch, crystalline cellulose, light anhydrous silicic acid, and the like. Examples of the lubricant include magnesium stearate, calcium stearate, talc, colloidal silica, and the like.
- Other features of the invention will become apparent in the course of the following descriptions of exemplary embodiments which are given for illustration of the invention and are not intended to be limiting thereof.
- Using CD2F1 mice (9-week-old or older) (CHARLES RIVER LABORATORIES JAPAN, INC) divided into a control group and a group burdened by insufficient sleep, an experiment was performed as shown in the experiment protocol of
FIG. 1A . - The insufficient sleep-burdened group was burdened by insufficient sleep for 24 hr by filling water in the breeding cage at the depth of 0.5 cm. The burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. The control group was reared without burden in the home cage. Thereafter, they were transferred into a cage set under a locomotor activity measurement infrared sensor (Digital acquisition system; NS-DAS-32, Neuroscience Inc, Tokyo, Japan) under fasting and water-deprivation. The locomotor activities in the former half (6 hr) of the dark phase were measured and the data was collected by a multidigital counter (Neuroscience Inc, Tokyo, Japan).
- The results are shown in
FIG. 1B . Since the insufficient sleep-burdened group showed a decrease in the locomotor activities in the former half of the dark phase (fatigue index) as compared to the control group, it was clarified that burden of insufficient sleep decreases the performance or induces fatigue. - Using CD2F1 mice (9-week-old or older) (CHARLES RIVER LABORATORIES JAPAN, INC) divided into a control group and an insufficient sleep-burdened group, an experiment was performed as shown in the experiment protocol of
FIG. 2A . - The insufficient sleep-burdened group was burdened by insufficient sleep for 48 hr by filling water in the breeding cage at the depth of 0.5 cm. The burden was released 6 hr after the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. The control group was reared without burden in the home cage. A Y-maze test was performed at 3 hr from the start of the dark phase, and short-working memory was measured.
- The results are shown in
FIG. 2B . Since the insufficient sleep-burdened group showed a decrease in the short-working memory (fatigue index) as compared to the control group, it was clarified that burden of insufficient sleep decreases the performance or induces fatigue. - Using CD2F1 mice (9-week-old or older) (CHARLES RIVER LABORATORIES JAPAN, INC) in the group constitution shown in Table 1, the effect was verified as shown in the experiment protocol of
FIG. 3A . -
TABLE 1 group No. group name His test substance X 1. solvent group − − 2. His group + − 3. test substance X group − + 4. combined use group + + - The His group and the combined use group were allowed to drink each solution freely for one week so that the dose of His would be 500 mg/kg/day. The test substance X group and the combined use group were made to ingest test substance X mixed in a feed or drinking water for one week so that the ingestion amount of Table 3 would be met. As the feed, a feed having the composition of Table 2 was used.
-
TABLE 2 Feed Composition composition composition (%) casein 20.0000 L-cystine 0.3000 cornstarch 39.7486 pregelatinized cornstarch 13.2000 sucrose 10.0000 soybean oil 7.0000 cellulose powder 5.0000 mineral mix (AIN-93G-MX) 3.5000 vitamin mix (AIN-93-MX) 1.0000 choline bitartrate 0.2500 tertiary butylhydroquinone 0.0014 - After ingestion of His and test substance X for one week, insufficient sleep was burdened for 24 hr by filling water in the breeding cage at the depth of 0.5 cm. The burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, they were transferred into a cage set under a locomotor activity measurement infrared sensor (Digital acquisition system; NS-DAS-32, Neuroscience Inc, Tokyo, Japan) under fasting and water-deprivation. The locomotor activities in the former half (6 hr) of the dark phase were measured and the data was collected by a multidigital counter (Neuroscience Inc, Tokyo, Japan).
- The results are shown in
FIG. 3B . In the combined use group to which His and vitamin B6 (VB6) were given for one week, locomotor activities were significantly improved in the former half of the dark phase as compared to the solvent group, and the locomotor activities tended to improve as compared to the His ingestion group, it was clarified that the combined use of His and vitamin B6 shows an anti-fatigue effect. - The combined use with carnosine was also examined in the same manner. The results are shown in
FIG. 3C . It was clarified that the combined use of His and carnosine also shows an anti-fatigue effect. On the other hand, other materials (7 materials) shown in Table 3 did not show an anti-fatigue effect whether each material was used alone or in combination with His. -
TABLE 3 anti-fatigue effect ingestion 3. 4. test amount 2. test combined substance X (mg/kg/day) His substance X use vitamin B12 6 x x x vitamin B1 50 x x x vitamin B6 300 x x ∘ DHA 700 x x x zinc 30 x x x creatine 400 x x x L-carnitine 500 x x x α-glycero- 600 x x x phosphocholine carnosine 1800 x x ∘ - From the above results, it was clarified that a composition containing histidine and vitamin B6 or carnosine has an anti-fatigue effect.
- Using CD2F1 mice (9-10-week-old) in the group constitution shown in Table 4, the test was performed as shown in the experiment protocol (
FIG. 4A ). -
TABLE 4 free drinking ingestion dose group amount (mg/kg/day) (mg/kg) No. group name His VB6 His VB6 1. solvent group — — — — 2. His group 900 — 900 — 3. VB6 group — 30 — 30 4. His + VB6 group 900 30 900 30 - The His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 30 mg/kg/day. As the feed, a feed having the composition of Table 5 was used.
-
TABLE 5 component (%) feed composition amino acid mix 20.0000 L-cystine 0.3000 cornstarch 39.7486 pregelatinized cornstarch 13.2000 sucrose 10.0000 soybean oil 7.0000 cellulose powder 5.0000 AIN-93G mineral mix 3.5000 AIN-93G vitamin mix 1.0000 choline bitartrate 0.2500 tertiary butylhydroquinone 0.0014 composition of amino acid mix Ala 2.25 Arg 3.28 Asn-H2O 3.60 Asp 3.16 Cys-Cys 0.50 Gln 12.04 Glu 9.16 Gly 1.62 His 0.51 Ile 4.45 Leu 8.13 Lys-HCl 8.82 Met 2.43 Phe 4.50 Pro 9.37 Ser 5.06 Thr 3.81 Trp 1.08 Tyr 4.85 Val 5.73 Starch 5.34 - After ingestion of His or VB6, or both for one week, insufficient sleep was burdened for 48 hr by filling water in the breeding cage at the depth of 0.5 cm. The burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, the His group and His+VB6 group were orally administered with His, and the VB6 group and His+VB6 group were orally administered with VB6 at 2 hr from the start of the dark phase after burden of insufficient sleep to achieve the doses in Table 4. A Y-maze test was performed at 3 hr from the start of the dark phase, and short-working memory was measured.
- The results are shown in
FIG. 4B . After burden of insufficient sleep that induces fatigue, the His+VB6 group showed a significant increase in the alternation behavior as compared to the solvent group or His group. - From the above results, it was clarified that the composition of the present invention containing His:VB6=30:1 has an anti-fatigue effect.
- Using CD2F1 mice (9-10-week-old) in the group is constitution shown in Table 6, the test was performed as shown in the experiment protocol (
FIG. 5A ). -
TABLE 6 free drinking ingestion dose group amount (mg/kg/day) (mg/kg) No. group name His VB6 His VB6 1. solvent group — — — — 2. His group 900 — 900 — 3. VB6 group — 7.5 — 7.5 4. His + VB6 group 900 7.5 900 7.5 - The His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 7.5 mg/kg/day. As the feed, a feed having the composition of Table 5 was used.
- After ingestion of His or VB6, or both for one week, insufficient sleep was burdened for 48 hr by filling water in the breeding cage at the depth of 0.5 cm. The burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, the His group and His+VB6 group were orally administered with His, and the VB6 group and His+VB6 group were orally administered with VB6 at 2 hr from the start of the dark phase after burden of insufficient sleep to achieve the doses in Table 6. A Y-maze test was performed at 3 hr from the start of the dark phase, and short-working memory was measured.
- The results are shown in
FIG. 5B . After burden of insufficient sleep that induces fatigue, the His+VB6 group showed a significant increase in the alternation behavior as compared to the solvent group or VB6 group, and an increase tendency in the alternation behavior as compared to the His group. - Example 4
- Using CD2F1 mice (9-10-week-old) in the group constitution shown in Table 6, the test was performed as shown in the experiment protocol (
FIG. 6A ). - The His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 7.5 mg/kg/day. As the feed, a feed having the composition of Table 5 was used.
- After ingestion of His or VB6, or both for one week, insufficient sleep was burdened for 24 hr by filling water in the breeding cage at the depth of 0.5 cm. The burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, the His group and His+VB6 group were orally administered with His, and the VB6 group and His+VB6 group were orally administered with VB6 at 1 hr before the start of the dark phase to achieve the doses in Table 6. The locomotor activities in the dark phase were measured by a multidigital counter (Neuroscience Inc., Tokyo, Japan).
- The results are shown in
FIG. 6B andFIG. 6C . At 4-5 hr after the start of the dark phase, the His+VB6 group showed a significant increase as compared to the solvent group, and an increase tendency as compared to the His group and the VB6 group. - From the results of Example 3 and Example 4, it was clarified that the composition of the present invention containing His:VB6=120:1 has an anti-fatigue effect.
- Using CD2F1 mice (10-21-week-old) in the group constitution shown in Table 7, the test was performed as shown in the experiment protocol (
FIG. 7A ). -
TABLE 7 free drinking ingestion dose group amount (mg/kg/day) (mg/kg) No. group name His VB6 His VB6 1. solvent group — — — — 2. His group 900 — 900 — 3. VB6 group — 2.5 — 2.5 4. His + VB6 group 900 2.5 900 2.5 - The His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 2.5 mg/kg/day. As the feed, a feed having the composition of Table 5 was used.
- After ingestion of His or VB6, or both for one week, insufficient sleep was burdened for 48 hr by filling water in the breeding cage at the depth of 0.5 cm. The burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, the His group and His+VB6 group were orally administered with His, and the VB6 group and His+VB6 group were orally administered with VB6 at 2 hr after the start of the doses in Table 7. A Y-maze test was performed at 3 hr from the start of the dark phase, and short-working memory was measured.
- The results are shown in
FIG. 7B . After burden of insufficient sleep that induces fatigue, the His+VB6 group and His group showed a significant increase in the alternation behavior as compared to the VB6 group, but no group showed a significant increase as compared to the solvent group. - Using CD2F1 mice (10-11-week-old) in the group constitution shown in Table 7, the test was performed as shown in the experiment protocol (
FIG. 8A ). - The His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 2.5 mg/kg/day. As the feed, a feed having the composition of Table 5 was used.
- After ingestion of His or VB6, or both for one week, insufficient sleep was burdened for 24 hr by filling water in the breeding cage at the depth of 0.5 cm. The burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, the His group and His+VB6 group were orally administered with His, and the VB6 group and His+VB6 group were orally administered with VB6 at 1 hr before the start of the dark phase to achieve the doses in Table 7. The locomotor activities in the dark phase were measured by a multidigital counter (Neuroscience Inc., Tokyo, Japan).
- The results are shown in
FIG. 8B . No group showed a significant increase in the activities as compared to the solvent group. - Using CD2F1 mice (10-21-week-old) in the group constitution shown in Table 8, the test was performed as shown in the experiment protocol (
FIG. 11A ). -
TABLE 8 free drinking ingestion dose group amount (mg/kg/day) (mg/kg) No. group name His VB6 His VB6 1. solvent group — — — — 2. His group 900 — 900 — 3. VB6 group — 3.0 — 3.0 4. His + VB6 group 900 3.0 900 3.0 - The His group and His+VB6 group were allowed to drink each solution freely for one week so that the ingestion amount of His would be 900 mg/kg/day, and the ingestion amount of the VB6 group and the His+VB6 group would be 3.0 mg/kg/day. As the feed, a feed having the composition of Table 5 was used.
- After ingestion of His or VB6, or both for one week, insufficient sleep was burdened for 48 hr by filling water in the breeding cage at the depth of 0.5 cm. The burden was released at 6 hr from the start of the light phase, and the mice were placed back in the home cage and allowed to rest for 6 hr. Thereafter, the His group and His+VB6 group were orally administered with His, and the VB6 group and His+VB6 group were orally administered with VB6 at 2 hr from the start of the dark phase after burden of insufficient sleep to achieve the doses in Table 8. A Y-maze test was performed at 3 hr from the start of the dark phase, and short-working memory was measured.
- The results are shown in
FIG. 11B . After burden of insufficient sleep that induces fatigue, the His+VB6 group showed a significant increase in the alternation behavior as compared to the solvent group. - A histidine and vitamin B6-containing tablet having the following combination is produced by tableting according to a conventional method. The tablet weight is 340 mg.
-
TABLE 9 each component combination ratio (%) L-histidine 76.048 starch syrup of reduced malt sugar 11.812 cellulose 9.506 calcium stearate 2 vitamin B6 0.634 total 100 - A histidine and vitamin B6-containing solution having the following combination is produced by a conventional method. The solution weight is 30 g.
-
TABLE 10 each component combination ratio (%) L-histidine 5.333 vitamin B6 0.050 sweetener 4.000 erythritol 10.000 high-intensity sweetener 0.013 citric acid 4.000 flavor 0.060 water 76.544 total 100.000 - Histidine and vitamin B6-containing granules having the following combination are produced by a conventional method. The volume is 2 g.
-
TABLE 11 each component combination ratio (%) L-histidine 80.000 vitamin B6 0.700 excipient 10.980 high-intensity sweetener 0.420 citric acid 6.400 flavor 1.500 total 100.000 - A histidine and vitamin B6-containing jelly having the following combination is produced by a conventional method. The weight is 100 g.
-
TABLE 12 each component combination ratio (%) L-histidine 1.600 vitamin B6 0.015 gellant 0.800 fruit juice 0.265 sweetener 2.500 high-intensity sweetener 0.023 citric acid 1.861 flavor 0.200 water 92.736 - Twenty males of 45 years old to less than 65 years old, who received total evaluation of not less than 17 points in the “self-diagnosis fatigue questionnaire” (Fatigue Science Laboratory Inc.), felt decrease in the quality of sleep (generally PSQI≥6), and obtained fatigue factor T scores of not less than 60 points in POMS, performed in advance, were selected, and randomly divided into 2 groups (10 per group). A crossover test, including ingesting histidine and control food (equal volume of cellulose) each for 14 days, was performed in each group.
- As shown in the experiment protocol of
FIG. 9A , the test subjects ingested capsules containing 1.65 g of L-histidine as a daily ingestion amount (5 capsules (hard capsule # 2 WHITE OP B/C) containing 0.33 g of L-histidine alone), or control sample capsules (5 capsules containing equal volume of cellulose) for 14 days. After the completion of 14 day ingestion, a 14 day resting period was taken. After the resting period, they ingested the capsules not ingested before the resting period. - On the initial day and the day after completion of the capsule ingestion period, the test subjects answered POMS and the VAS questionnaires (fatigue, depression, vague sense, drowsiness, clear thinking, motivation, attentiveness, concentration) relating to fatigue, and cognitive function measurement task CogHealth (under higher difficulty conditions by simultaneously including mental arithmetic task as well) to measure intellectual performance which is one of the fatigue indices. Furthermore, they answered VAS questionnaires after completion of CogHealth. Evaluation after completion of CogHealth reveals the differency of the state between after and before the work-load.
- The results are shown in
FIGS. 9B to 9E . As compared to the test subjects who ingested the control food, the fatigue factor scores of POMS significantly decreased (paired t-test: p<0.05) (FIG. 9B ) and the sense of clear thinking, motivation, and attentiveness significantly increased (paired t-test: p<0.05) in VAS questionnaires relating to fatigue (FIG. 9C ) in the test subjects who ingested histidine for 14 days. In the intellectual work efficiency, ingestion of histidine shortened the reaction time of cognitive function measurement task and significantly decreased the reaction time of delayed recall task (paired t-test: p<0.05) as compared to ingestion of the control food (FIG. 9D ). In VAS questionnaires after completion of CogHealth, moreover, the sense of depression significantly decreased and the sense of motivation and attentiveness significantly increased (paired t-test: p<0.05) (FIG. 9E ). This means that an increase in motivation and attentiveness can be maintained, and feeling of depression by burden can be suppressed, even when cognitive work is loaded. - From the above results, it was clarified that an agent containing histidine can improve/recover fatigue.
- Twenty males of 45 years old to less than 65 years old, who received total evaluation of not less than 17 points in the “self-diagnosis fatigue questionnaire” (Fatigue Science Laboratory Inc.), felt decrease in the quality of sleep (generally PSQI≥6), and obtained fatigue factor T scores of not less than 60 points in POMS performed in advance, were selected, and randomly divided into 2 groups (10 per group). The effect of single ingestion of histidine and control food (equal volume of cellulose) was compared in each group.
- As shown in the experiment protocol of
FIG. 10A , the test subjects took the same meals for 3 days before the experiment, fasted for 10 to for 14 hr, and ingested capsules containing 1.65 g of L-histidine as a single ingestion amount (5 capsules (hard capsule # 2 WHITE OP B/C) containing 0.33 g of L-histidine alone), or control sample capsules (5 capsules containing equal volume of cellulose). - Before and 1 hr after ingestion of capsules, the test subjects answered the VAS questionnaires (fatigue, depression, vague sense, drowsiness, clear thinking, motivation, attentiveness, concentration) relating to fatigue, and cognitive function measurement task CogHealth (under higher difficulty conditions by simultaneously including mental arithmetic task as well) to measure intellectual performance which is one of the fatigue indices. Furthermore, they answered VAS questionnaires after completion of CogHealth. Evaluation after completion of CogHealth reveals the defferency of the state between after and before the work-load.
- The results are shown in
FIGS. 10B and 10C . It was found that the work time in 5 kinds of brain function measurement indices was shortened in the test subjects who ingested histidine, as compared to the test subjects who ingested the control food. In VAS questionnaires relating to fatigue, the sense of clear thinking and attentiveness significantly increased and the sense of concentration tended to increase (paired t-test: p<0.05) (FIG. 10B ). In VAS questionnaires after completion of CogHealth, moreover, the sense of vague sense significantly decreased, the sense of depression tended to decrease, and the sense of concentration tended to increase (paired t-test: p<0.05) (FIG. 10C ). This means that ingestion of histidine may be able to suppress vague sense and the sense of depression due to burden and maintain concentration, even when cognitive work is loaded. - From the above results, it was clarified that an agent containing histidine can improve/recover fatigue.
- As mentioned above, continuous ingestion of histidine for 2 weeks showed improvement/recovery of fatigue, and a single ingestion of His showed improvement/recovery of fatigue. Ingestion of His did not show problematic variation in general properties, hematology, and blood biochemistry from the aspects of safety.
- Fatigue (mental fatigue, physical fatigue) can be improved by ingesting the composition of the present invention comprising (1) histidine and (2) vitamin B6 and/or carnosine. Since the active ingredients thereof are amino acid (peptide) and vitamin, the present invention has less fear of causing side effects, is superior in safety, and can be consecutively used every day.
- Where a numerical limit or range is stated herein, the endpoints are included. Also, all values and subranges within a numerical limit or range are specifically included as if explicitly written out.
- As used herein the words “a” and “an” and the like carry the meaning of “one or more.”
- Obviously, numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that, within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein.
- All patents and other references mentioned above are incorporated in full herein by this reference, the same as if set forth at length.
Claims (2)
1. An anti-fatigue composition, comprising (1) histidine and (2) vitamin B6 and/or carnosine in combination.
2-44. (canceled)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16/825,017 US20200215086A1 (en) | 2013-10-09 | 2020-03-20 | Anti-fatigue composition |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2013212329 | 2013-10-09 | ||
JP2013-212329 | 2013-10-09 | ||
PCT/JP2014/076989 WO2015053336A1 (en) | 2013-10-09 | 2014-10-08 | Anti-fatigue composition |
US15/093,207 US10369163B2 (en) | 2013-10-09 | 2016-04-07 | Anti-fatigue composition |
US16/446,937 US20190365787A1 (en) | 2013-10-09 | 2019-06-20 | Anti-fatigue composition |
US16/825,017 US20200215086A1 (en) | 2013-10-09 | 2020-03-20 | Anti-fatigue composition |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US16/446,937 Continuation US20190365787A1 (en) | 2013-10-09 | 2019-06-20 | Anti-fatigue composition |
Publications (1)
Publication Number | Publication Date |
---|---|
US20200215086A1 true US20200215086A1 (en) | 2020-07-09 |
Family
ID=52813151
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/093,207 Expired - Fee Related US10369163B2 (en) | 2013-10-09 | 2016-04-07 | Anti-fatigue composition |
US16/446,937 Abandoned US20190365787A1 (en) | 2013-10-09 | 2019-06-20 | Anti-fatigue composition |
US16/825,017 Abandoned US20200215086A1 (en) | 2013-10-09 | 2020-03-20 | Anti-fatigue composition |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/093,207 Expired - Fee Related US10369163B2 (en) | 2013-10-09 | 2016-04-07 | Anti-fatigue composition |
US16/446,937 Abandoned US20190365787A1 (en) | 2013-10-09 | 2019-06-20 | Anti-fatigue composition |
Country Status (5)
Country | Link |
---|---|
US (3) | US10369163B2 (en) |
EP (1) | EP3078375B1 (en) |
JP (2) | JP6634825B2 (en) |
CN (2) | CN105611926A (en) |
WO (1) | WO2015053336A1 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015053336A1 (en) * | 2013-10-09 | 2015-04-16 | 味の素株式会社 | Anti-fatigue composition |
JP7136635B2 (en) * | 2018-09-05 | 2022-09-13 | 株式会社 伊藤園 | Method for evaluating the suppressive effect of green tea components on cognitive function decline associated with workload |
CN109965288A (en) * | 2019-04-30 | 2019-07-05 | 广西信业生物技术有限公司 | It is a kind of for resisting kinetic fatigue, accelerate the composition and preparation method thereof of fatigue recovery |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6420342B1 (en) * | 2000-05-08 | 2002-07-16 | N.V. Nutricia | Nutritional preparation comprising ribose and medical use thereof |
US20060093649A1 (en) * | 2002-10-11 | 2006-05-04 | Ajinomoto Co., Inc. | Food composition for recovery from fatigue |
US20060115556A1 (en) * | 2004-12-01 | 2006-06-01 | Foulger Sidney W | Nutritional supplement drink containing xanthone extracts |
US10369163B2 (en) * | 2013-10-09 | 2019-08-06 | Ajinomoto Co., Inc. | Anti-fatigue composition |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2970957B2 (en) * | 1991-05-15 | 1999-11-02 | 株式会社グレイトチレン | Refined pollen nutritional preparation |
JPH0920661A (en) * | 1995-07-04 | 1997-01-21 | Suntory Ltd | Learning ability-improving composition |
DE69942803D1 (en) * | 1998-07-22 | 2010-11-11 | Smithkline Beecham Ltd | REDEEM AND WITH CODING CDNS |
US6479545B1 (en) * | 1999-09-30 | 2002-11-12 | Drugtech Corporation | Formulation for menopausal women |
JP2001172189A (en) * | 1999-12-15 | 2001-06-26 | Pola Chem Ind Inc | Enhancer of limited movement quantity |
US6855727B2 (en) * | 2000-12-04 | 2005-02-15 | Yaizu Suisankagaku Industry Co., Ltd. | Muscular fatigue-controlling composition and method for providing muscular fatigue-controlling effect |
WO2002067959A1 (en) | 2001-02-27 | 2002-09-06 | Neurotide Co., Ltd. | Peptide derived from yeast having activities as anti-tsress, anti-fatigue and brain neurotrophic factor and relaxing premenstrual syndrome and menstrual pain, and prepairing process thereof |
JP3899436B2 (en) * | 2002-05-10 | 2007-03-28 | フォーデイズ株式会社 | Healthy drink with water soluble nucleoprotein |
US20060021172A1 (en) * | 2004-08-02 | 2006-02-02 | Learned Addison W Iii | Isokinetic paintbrush control handle |
JP4792730B2 (en) | 2004-11-12 | 2011-10-12 | 味の素株式会社 | Anti-fatigue composition |
US20060211721A1 (en) * | 2005-03-21 | 2006-09-21 | Roberts Alan R | Nutraceutical formulation of a cognitive enhancement system |
JP5210636B2 (en) * | 2005-10-04 | 2013-06-12 | 協和発酵バイオ株式会社 | Composition for improving subjective symptoms of fatigue |
JP2007131605A (en) * | 2005-11-14 | 2007-05-31 | Kanebo Foods Ltd | Indefinite complaint-improving composition and food |
WO2007070454A2 (en) * | 2005-12-09 | 2007-06-21 | Novalife | High protein supplement |
US7982066B2 (en) * | 2005-12-09 | 2011-07-19 | Novalife, Inc. | High protein supplement |
EP1835287A3 (en) | 2006-03-14 | 2007-10-24 | Wilfried P. Bieger | Method and test kits for determining neuroendocrinal diseases |
JP5114399B2 (en) * | 2006-06-27 | 2013-01-09 | 興和株式会社 | Drugs for fatigue prevention and / or recovery |
CN101842094A (en) * | 2007-10-31 | 2010-09-22 | 明治乳业株式会社 | Anti-fatigue agent comprising amino acid composition |
CN102318795A (en) * | 2011-10-19 | 2012-01-18 | 郭景龙 | Health-care food having anti-fatigue function |
JP5968664B2 (en) | 2012-04-04 | 2016-08-10 | 株式会社ニトムズ | Cleaning adhesive tape roll |
-
2014
- 2014-10-08 WO PCT/JP2014/076989 patent/WO2015053336A1/en active Application Filing
- 2014-10-08 JP JP2015541619A patent/JP6634825B2/en active Active
- 2014-10-08 CN CN201480055604.4A patent/CN105611926A/en active Pending
- 2014-10-08 EP EP14851920.0A patent/EP3078375B1/en not_active Revoked
- 2014-10-08 CN CN202010731123.8A patent/CN111743999A/en active Pending
-
2016
- 2016-04-07 US US15/093,207 patent/US10369163B2/en not_active Expired - Fee Related
-
2019
- 2019-06-20 US US16/446,937 patent/US20190365787A1/en not_active Abandoned
- 2019-12-18 JP JP2019228138A patent/JP2020072673A/en active Pending
-
2020
- 2020-03-20 US US16/825,017 patent/US20200215086A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6420342B1 (en) * | 2000-05-08 | 2002-07-16 | N.V. Nutricia | Nutritional preparation comprising ribose and medical use thereof |
US20060093649A1 (en) * | 2002-10-11 | 2006-05-04 | Ajinomoto Co., Inc. | Food composition for recovery from fatigue |
US20060115556A1 (en) * | 2004-12-01 | 2006-06-01 | Foulger Sidney W | Nutritional supplement drink containing xanthone extracts |
US10369163B2 (en) * | 2013-10-09 | 2019-08-06 | Ajinomoto Co., Inc. | Anti-fatigue composition |
Also Published As
Publication number | Publication date |
---|---|
EP3078375A4 (en) | 2017-04-05 |
US10369163B2 (en) | 2019-08-06 |
US20190365787A1 (en) | 2019-12-05 |
EP3078375A1 (en) | 2016-10-12 |
JPWO2015053336A1 (en) | 2017-03-09 |
JP2020072673A (en) | 2020-05-14 |
JP6634825B2 (en) | 2020-01-22 |
CN111743999A (en) | 2020-10-09 |
WO2015053336A1 (en) | 2015-04-16 |
CN105611926A (en) | 2016-05-25 |
US20160287616A1 (en) | 2016-10-06 |
EP3078375B1 (en) | 2021-05-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20200215086A1 (en) | Anti-fatigue composition | |
JP6255079B2 (en) | Rapid-acting oral arginine level oral preparation containing citrulline and arginine | |
JP2002322063A (en) | Composition for relieving mental fatigue, composition for maintaining and enhancing concentration power, and composition for maintaining and enhancing mental vitality | |
JP7047865B2 (en) | Foods containing histidine and their uses | |
EP3115047B1 (en) | Debility preventative | |
US9480668B2 (en) | Blood flow promoting agent | |
US20060094734A1 (en) | Composition and method for inducing alertness | |
JP7103363B2 (en) | Composition for prevention or improvement of hand-foot syndrome | |
JP6344059B2 (en) | Physiological action enhancer of caffeine | |
JP7257715B2 (en) | oral composition | |
US11045437B2 (en) | Composition for improving brain function | |
JP2015149919A (en) | beverage |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |