TW201733607A - Composition for preventing neurological diseases - Google Patents
Composition for preventing neurological diseases Download PDFInfo
- Publication number
- TW201733607A TW201733607A TW106100494A TW106100494A TW201733607A TW 201733607 A TW201733607 A TW 201733607A TW 106100494 A TW106100494 A TW 106100494A TW 106100494 A TW106100494 A TW 106100494A TW 201733607 A TW201733607 A TW 201733607A
- Authority
- TW
- Taiwan
- Prior art keywords
- peptide
- animal
- composition
- neurological disease
- preventive
- Prior art date
Links
- 208000012902 Nervous system disease Diseases 0.000 title claims abstract description 86
- 208000025966 Neurological disease Diseases 0.000 title claims abstract description 86
- 239000000203 mixture Substances 0.000 title claims abstract description 70
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 174
- 241001465754 Metazoa Species 0.000 claims abstract description 95
- 238000000034 method Methods 0.000 claims abstract description 26
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 17
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 17
- 206010012289 Dementia Diseases 0.000 claims abstract description 15
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 13
- 239000000463 material Substances 0.000 claims abstract description 10
- 241000196324 Embryophyta Species 0.000 claims description 67
- 108010046377 Whey Proteins Proteins 0.000 claims description 44
- 230000003449 preventive effect Effects 0.000 claims description 44
- 102000007544 Whey Proteins Human genes 0.000 claims description 43
- 239000005862 Whey Substances 0.000 claims description 40
- 235000010469 Glycine max Nutrition 0.000 claims description 39
- 244000068988 Glycine max Species 0.000 claims description 38
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 33
- 230000000694 effects Effects 0.000 claims description 19
- 210000000274 microglia Anatomy 0.000 claims description 18
- 230000002265 prevention Effects 0.000 claims description 17
- 235000013311 vegetables Nutrition 0.000 claims description 17
- 239000004480 active ingredient Substances 0.000 claims description 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- 210000002569 neuron Anatomy 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 208000018737 Parkinson disease Diseases 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 230000028327 secretion Effects 0.000 claims description 4
- 230000009471 action Effects 0.000 claims description 3
- 230000002718 inhibitory effect on inflammation Effects 0.000 claims 1
- 206010034010 Parkinsonism Diseases 0.000 abstract description 9
- 238000010438 heat treatment Methods 0.000 description 62
- 239000000047 product Substances 0.000 description 50
- 238000011282 treatment Methods 0.000 description 41
- 108010016626 Dipeptides Proteins 0.000 description 31
- 125000004122 cyclic group Chemical group 0.000 description 30
- 150000003839 salts Chemical class 0.000 description 23
- 238000000354 decomposition reaction Methods 0.000 description 17
- 239000007788 liquid Substances 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 235000013305 food Nutrition 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 230000002025 microglial effect Effects 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 206010061218 Inflammation Diseases 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- XWYXUMDVQIOAPR-UHFFFAOYSA-N (3S,6S)-3,6-Diisobutyl-2,5-dioxohexahydropyrazine Natural products CC(C)CC1NC(=O)C(CC(C)C)NC1=O XWYXUMDVQIOAPR-UHFFFAOYSA-N 0.000 description 6
- QPDMOMIYLJMOQJ-UHFFFAOYSA-N Cyclo-L-leu-L-phe Natural products N1C(=O)C(CC(C)C)NC(=O)C1CC1=CC=CC=C1 QPDMOMIYLJMOQJ-UHFFFAOYSA-N 0.000 description 6
- 235000019658 bitter taste Nutrition 0.000 description 6
- XWYXUMDVQIOAPR-UWVGGRQHSA-N cyclo(L-leucyl-L-leucyl) Chemical compound CC(C)C[C@@H]1NC(=O)[C@H](CC(C)C)NC1=O XWYXUMDVQIOAPR-UWVGGRQHSA-N 0.000 description 6
- QPDMOMIYLJMOQJ-STQMWFEESA-N cyclo(L-phenylalanyl-L-leucyl) Chemical compound N1C(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CC1=CC=CC=C1 QPDMOMIYLJMOQJ-STQMWFEESA-N 0.000 description 6
- 108010048344 cyclo(leucyl-phenylalanyl) Proteins 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- BZUNCDPEEKFTCX-GJZGRUSLSA-N (3s,6s)-3-(1h-indol-3-ylmethyl)-6-(2-methylpropyl)piperazine-2,5-dione Chemical compound N1C(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CC1=CNC2=CC=CC=C12 BZUNCDPEEKFTCX-GJZGRUSLSA-N 0.000 description 5
- QZBUWPVZSXDWSB-UHFFFAOYSA-N 3-benzyl-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1N2CCCC2C(=O)NC1CC1=CC=CC=C1 QZBUWPVZSXDWSB-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 108010027501 cyclo(leucyl-prolyl) Proteins 0.000 description 5
- 108010038252 cyclo(phenylalanyl-prolyl) Proteins 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- SZJNCZMRZAUNQT-UHFFFAOYSA-N (3R,8aS)-hexahydro-3-(2-methylpropyl)pyrrolo[1,2-a]pyrazine-1,4-dione Natural products O=C1C(CC(C)C)NC(=O)C2CCCN21 SZJNCZMRZAUNQT-UHFFFAOYSA-N 0.000 description 4
- CHYMARRIVIIBNV-UWVGGRQHSA-N (3S,6S)-3-(4-Hydroxybenzyl)-6-(hydroxymethyl)-2,5-piperazinedione Chemical compound N1C(=O)[C@H](CO)NC(=O)[C@@H]1CC1=CC=C(O)C=C1 CHYMARRIVIIBNV-UWVGGRQHSA-N 0.000 description 4
- IFQZEERDQXQTLJ-NSHDSACASA-N Cyclo(glycyltryptophyl) Chemical compound N1C(=O)CNC(=O)[C@@H]1CC1=CNC2=CC=CC=C12 IFQZEERDQXQTLJ-NSHDSACASA-N 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- SZJNCZMRZAUNQT-IUCAKERBSA-N cyclo(L-Leu-L-Pro) Chemical compound O=C1[C@H](CC(C)C)NC(=O)[C@@H]2CCCN21 SZJNCZMRZAUNQT-IUCAKERBSA-N 0.000 description 4
- 108010012664 cyclo(seryltyrosyl) Proteins 0.000 description 4
- -1 placenta Proteins 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 235000021119 whey protein Nutrition 0.000 description 4
- UBLWFFBGMBRBMC-VQVTYTSYSA-N (3S,8aS)-3-[(1R)-1-hydroxyethyl]-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1[C@H]([C@H](O)C)NC(=O)[C@@H]2CCCN21 UBLWFFBGMBRBMC-VQVTYTSYSA-N 0.000 description 3
- 241000209094 Oryza Species 0.000 description 3
- 244000000231 Sesamum indicum Species 0.000 description 3
- 235000003434 Sesamum indicum Nutrition 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000005018 casein Substances 0.000 description 3
- 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 3
- 235000021240 caseins Nutrition 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- OQQPOHUVAQPSHJ-UHFFFAOYSA-N (3S,6S)-3-(1-methylethyl)-6-(phenylmethyl)piperazine-2,5-dione Natural products N1C(=O)C(C(C)C)NC(=O)C1CC1=CC=CC=C1 OQQPOHUVAQPSHJ-UHFFFAOYSA-N 0.000 description 2
- QGMAWEIDGADSAC-YUMQZZPRSA-N (3s,6s)-3,6-di(propan-2-yl)piperazine-2,5-dione Chemical compound CC(C)[C@@H]1NC(=O)[C@H](C(C)C)NC1=O QGMAWEIDGADSAC-YUMQZZPRSA-N 0.000 description 2
- WWISPHBAYBECQZ-IMJSIDKUSA-N (3s,6s)-3,6-dimethylpiperazine-2,5-dione Chemical compound C[C@@H]1NC(=O)[C@H](C)NC1=O WWISPHBAYBECQZ-IMJSIDKUSA-N 0.000 description 2
- CWFHBXSYJWIDIY-UWVGGRQHSA-N (3s,6s)-3-(4-aminobutyl)-6-(2-methylpropyl)piperazine-2,5-dione Chemical compound CC(C)C[C@@H]1NC(=O)[C@H](CCCCN)NC1=O CWFHBXSYJWIDIY-UWVGGRQHSA-N 0.000 description 2
- ZJDMXAAEAVGGSK-ROUUACIJSA-N (3s,6s)-3-[(4-hydroxyphenyl)methyl]-6-(1h-indol-3-ylmethyl)piperazine-2,5-dione Chemical compound C1=CC(O)=CC=C1C[C@H]1C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N1 ZJDMXAAEAVGGSK-ROUUACIJSA-N 0.000 description 2
- OQQPOHUVAQPSHJ-RYUDHWBXSA-N (3s,6s)-3-benzyl-6-propan-2-ylpiperazine-2,5-dione Chemical compound N1C(=O)[C@H](C(C)C)NC(=O)[C@@H]1CC1=CC=CC=C1 OQQPOHUVAQPSHJ-RYUDHWBXSA-N 0.000 description 2
- DBJPZCJQDRPOME-BQBZGAKWSA-N (3s,6s)-3-methyl-6-(2-methylpropyl)piperazine-2,5-dione Chemical compound CC(C)C[C@@H]1NC(=O)[C@H](C)NC1=O DBJPZCJQDRPOME-BQBZGAKWSA-N 0.000 description 2
- ZDACRNZBFJOLTC-CIUDSAMLSA-N (3s,8as)-3-[(2s)-butan-2-yl]-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CCCN21 ZDACRNZBFJOLTC-CIUDSAMLSA-N 0.000 description 2
- PNSKRAHOHQWAAN-WHFBIAKZSA-N 3-[(2s,5s)-5-methyl-3,6-dioxopiperazin-2-yl]propanamide Chemical compound C[C@@H]1NC(=O)[C@H](CCC(N)=O)NC1=O PNSKRAHOHQWAAN-WHFBIAKZSA-N 0.000 description 2
- WYBVBIHNJWOLCJ-IUCAKERBSA-N Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCNC(N)=N WYBVBIHNJWOLCJ-IUCAKERBSA-N 0.000 description 2
- CKAJHWFHHFSCDT-WHFBIAKZSA-N Asp-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(O)=O CKAJHWFHHFSCDT-WHFBIAKZSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- DBJPZCJQDRPOME-UHFFFAOYSA-N DL-alanyl-leucyl anhydride Natural products CC(C)CC1NC(=O)C(C)NC1=O DBJPZCJQDRPOME-UHFFFAOYSA-N 0.000 description 2
- YBTCBQBIJKGSJP-BQBZGAKWSA-N Glu-Pro Chemical compound OC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O YBTCBQBIJKGSJP-BQBZGAKWSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- QGMAWEIDGADSAC-UHFFFAOYSA-N L-Valyl-L-valine anhydride Natural products CC(C)C1NC(=O)C(C(C)C)NC1=O QGMAWEIDGADSAC-UHFFFAOYSA-N 0.000 description 2
- WYBVBIHNJWOLCJ-UHFFFAOYSA-N N-L-arginyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCCN=C(N)N WYBVBIHNJWOLCJ-UHFFFAOYSA-N 0.000 description 2
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 244000046052 Phaseolus vulgaris Species 0.000 description 2
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 2
- 108010073771 Soybean Proteins Proteins 0.000 description 2
- YKRQRPFODDJQTC-CSMHCCOUSA-N Thr-Lys Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN YKRQRPFODDJQTC-CSMHCCOUSA-N 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000010724 Wisteria floribunda Nutrition 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 108010038633 aspartylglutamate Proteins 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000005352 clarification Methods 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- JUAPMRSLDANLAS-HOTGVXAUSA-N cyclo(L-phenylalanyl-L-phenylalanyl) Chemical compound C([C@@H]1NC([C@@H](NC1=O)CC=1C=CC=CC=1)=O)C1=CC=CC=C1 JUAPMRSLDANLAS-HOTGVXAUSA-N 0.000 description 2
- 108010041457 cyclo(alanyl-leucyl) Proteins 0.000 description 2
- 108010015607 cyclo(alanylalanyl) Proteins 0.000 description 2
- 108010046166 cyclo(glycyltryptophyl) Proteins 0.000 description 2
- 108010039669 cyclo(phenylalanyl-phenylalanyl) Proteins 0.000 description 2
- WWISPHBAYBECQZ-UHFFFAOYSA-N cyclo-L-Ala-L-Ala Natural products CC1NC(=O)C(C)NC1=O WWISPHBAYBECQZ-UHFFFAOYSA-N 0.000 description 2
- JUAPMRSLDANLAS-UHFFFAOYSA-N cyclo-L-Phe-L-Phe Natural products O=C1NC(CC=2C=CC=CC=2)C(=O)NC1CC1=CC=CC=C1 JUAPMRSLDANLAS-UHFFFAOYSA-N 0.000 description 2
- ZJDMXAAEAVGGSK-UHFFFAOYSA-N cyclo-L-Trp-L-Phe Natural products C1=CC(O)=CC=C1CC1C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)N1 ZJDMXAAEAVGGSK-UHFFFAOYSA-N 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000019710 soybean protein Nutrition 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- VQFHWKRNHGHZTK-LURJTMIESA-N (3s)-3-(2-methylpropyl)piperazine-2,5-dione Chemical compound CC(C)C[C@@H]1NC(=O)CNC1=O VQFHWKRNHGHZTK-LURJTMIESA-N 0.000 description 1
- UZOJHXFWJFSFAI-VIFPVBQESA-N (3s)-3-benzylpiperazine-2,5-dione Chemical compound N1C(=O)CNC(=O)[C@@H]1CC1=CC=CC=C1 UZOJHXFWJFSFAI-VIFPVBQESA-N 0.000 description 1
- HLXXMJDWTBXTOR-STQMWFEESA-N (3s,6s)-3-benzyl-6-(1h-imidazol-5-ylmethyl)piperazine-2,5-dione Chemical compound C([C@@H]1NC([C@@H](NC1=O)CC=1NC=NC=1)=O)C1=CC=CC=C1 HLXXMJDWTBXTOR-STQMWFEESA-N 0.000 description 1
- WIJKWEYCUNYTGY-UWVGGRQHSA-N (3s,6s)-3-benzyl-6-(hydroxymethyl)piperazine-2,5-dione Chemical compound N1C(=O)[C@H](CO)NC(=O)[C@@H]1CC1=CC=CC=C1 WIJKWEYCUNYTGY-UWVGGRQHSA-N 0.000 description 1
- VFVAGPWBFWJBMN-YUMQZZPRSA-N (3s,8as)-3-(2-methylsulfanylethyl)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1[C@H](CCSC)NC(=O)[C@@H]2CCCN21 VFVAGPWBFWJBMN-YUMQZZPRSA-N 0.000 description 1
- OWOHLURDBZHNGG-YFKPBYRVSA-N (8ar)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1CNC(=O)[C@@H]2CCCN12 OWOHLURDBZHNGG-YFKPBYRVSA-N 0.000 description 1
- VNHJXYUDIBQDDX-UWVGGRQHSA-N 2-[(2s,5s)-5-benzyl-3,6-dioxopiperazin-2-yl]acetic acid Chemical compound N1C(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CC1=CC=CC=C1 VNHJXYUDIBQDDX-UWVGGRQHSA-N 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101100381940 Acidianus ambivalens bps2 gene Proteins 0.000 description 1
- WSLYCILIEOFQPK-UHFFFAOYSA-N Ala-Pro-diketopiperazine Natural products O=C1C(C)NC(=O)C2CCCN21 WSLYCILIEOFQPK-UHFFFAOYSA-N 0.000 description 1
- 241001107116 Castanospermum australe Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- LSGOTAXPWMCUCK-UHFFFAOYSA-N D-prolyl-L-tyrosine anhydride Natural products C1=CC(O)=CC=C1CC1C(=O)N2CCCC2C(=O)N1 LSGOTAXPWMCUCK-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 244000017020 Ipomoea batatas Species 0.000 description 1
- 235000002678 Ipomoea batatas Nutrition 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- NVGBPTNZLWRQSY-UWVGGRQHSA-N Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN NVGBPTNZLWRQSY-UWVGGRQHSA-N 0.000 description 1
- QCZYYEFXOBKCNQ-STQMWFEESA-N Lys-Phe Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 QCZYYEFXOBKCNQ-STQMWFEESA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- WCRFXRIWBFRZBR-GGVZMXCHSA-N Thr-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 WCRFXRIWBFRZBR-GGVZMXCHSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- GIAZPLMMQOERPN-YUMQZZPRSA-N Val-Pro Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(O)=O GIAZPLMMQOERPN-YUMQZZPRSA-N 0.000 description 1
- 240000001417 Vigna umbellata Species 0.000 description 1
- 235000011453 Vigna umbellata Nutrition 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000019606 astringent taste Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000021279 black bean Nutrition 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000011449 brick Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- WSLYCILIEOFQPK-WDSKDSINSA-N cis-Cyclo[L-Ala-L-Pro] Chemical compound O=C1[C@H](C)NC(=O)[C@@H]2CCCN21 WSLYCILIEOFQPK-WDSKDSINSA-N 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- UZOJHXFWJFSFAI-SECBINFHSA-N cyclic glycylphenylalanine Natural products N1C(=O)CNC(=O)[C@H]1CC1=CC=CC=C1 UZOJHXFWJFSFAI-SECBINFHSA-N 0.000 description 1
- NAKUGCPAQTUSBE-IUCAKERBSA-N cyclo(L-His-L-Pro) Chemical compound C([C@@H]1NC([C@@H]2CCCN2C1=O)=O)C1=CN=CN1 NAKUGCPAQTUSBE-IUCAKERBSA-N 0.000 description 1
- 108010048643 cyclo(aspartyl-phenylalanyl) Proteins 0.000 description 1
- 108010001140 cyclo(glycylprolyl) Proteins 0.000 description 1
- 108010021250 cyclo(leucylglycine) Proteins 0.000 description 1
- WIJKWEYCUNYTGY-UHFFFAOYSA-N cyclo-L-Phe-L-Ser Natural products N1C(=O)C(CO)NC(=O)C1CC1=CC=CC=C1 WIJKWEYCUNYTGY-UHFFFAOYSA-N 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000002768 hair cell Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 108010017068 histidyl-proline diketopiperazine Proteins 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 108010038320 lysylphenylalanine Proteins 0.000 description 1
- LSGOTAXPWMCUCK-RYUDHWBXSA-N maculosin Chemical compound C1=CC(O)=CC=C1C[C@H]1C(=O)N2CCC[C@H]2C(=O)N1 LSGOTAXPWMCUCK-RYUDHWBXSA-N 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 108010091748 peptide A Proteins 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical group O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
- A23L33/185—Vegetable proteins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
- A23L33/19—Dairy proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/20—Milk; Whey; Colostrum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Public Health (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Medical Informatics (AREA)
- Virology (AREA)
- Developmental Biology & Embryology (AREA)
- Microbiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Botany (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
本發明係有關於一種神經性疾病之預防用組成物。更詳而言之，係有關於一種含有動植物性胜肽熱處理物作為有效成分的神經性疾病之預防用組成物、用以預防神經性疾病之動植物性胜肽熱處理物的使用、及利用動植物性胜肽熱處理物的神經性疾病之預防方法。 The present invention relates to a composition for preventing neurological diseases. More specifically, it relates to a preventive composition for a neurological disease containing a heat-treated product of an animal or plant peptide as an active ingredient, use of a heat-treated animal or plant peptide for preventing a neurological disease, and utilization of animal and plant properties. A method for preventing neurological diseases of a peptide heat-treated product.
隨著高齡化社會的到來，神經性疾病患者數的增加在現代社會中已成嚴重問題。前述神經性疾病係一種起因於存在於腦或脊髓之特定神經細胞群的機能降低或死亡所衍生的疾病。作為代表性的神經性疾病，可舉出失智症、精神分裂症、阿茲海默症、帕金森綜合症、肌肉萎縮性脊髓側索硬化症等。已有人報導這些神經性疾病的發病係與起因於小神經膠質細胞的活化之神經細胞的發炎有關(非專利文獻1及2)。例如，非專利文獻3及4中報導，小神經膠質細胞的活化涉及失智症或精神分裂症的發病。又，非專利文獻5及6中報導，起因於伴隨小神經膠質細胞的活化而分泌的一氧化氮或發炎性細胞激素之神經細胞的發 炎涉及阿茲海默症或帕金森綜合症的發病。再者，亦有人報導小神經膠質細胞涉及肌肉萎縮性脊髓側索硬化症(非專利文獻7)。 With the advent of an aging society, the increase in the number of patients with neurological diseases has become a serious problem in modern society. The aforementioned neurological disease is a disease caused by a decrease or death of a function of a specific nerve cell group existing in the brain or the spinal cord. Typical neurological diseases include dementia, schizophrenia, Alzheimer's disease, Parkinson's syndrome, and amyotrophic lateral sclerosis. It has been reported that the onset of these neurological diseases is related to inflammation of nerve cells caused by activation of microglia (Non-Patent Documents 1 and 2). For example, it is reported in Non-Patent Documents 3 and 4 that activation of microglia involves the onset of dementia or schizophrenia. Further, Non-Patent Documents 5 and 6 report that hair cells derived from nitric oxide or inflammatory cytokines secreted by activation of microglia are involved. Inflammation involves the onset of Alzheimer's disease or Parkinson's disease. Furthermore, it has also been reported that microglia are involved in amyotrophic lateral sclerosis (Non-Patent Document 7).
前述神經性疾病由於有潛伏期長，且發病後不易治療之特性，因此發病前的預防極為重要。另一方面，自神經性疾病發病前長期攝取人工合成的化合物，由於有表現無法預期之副作用的疑慮，因而不佳。從而，便企望開發出一種安全且能長期攝取的有效成分。 Since the aforementioned neurological disease has a long incubation period and is not easily treated after the onset of the disease, prevention before the onset is extremely important. On the other hand, long-term intake of artificially synthesized compounds from the onset of neurological diseases is not good due to doubts about unpredictable side effects. Therefore, it is expected to develop an effective ingredient that is safe and can be ingested for a long period of time.
[非專利文獻1] Cell, 140(6), 918-934 (2010) [Non-Patent Document 1] Cell, 140(6), 918-934 (2010)
[非專利文獻2] 福岡醫誌，100(7), 243-247 (2009) [Non-Patent Document 2] Fukuoka Medical Journal, 100(7), 243-247 (2009)
[非專利文獻3] 慢性發炎與精神分裂症，分子精神醫學，Vol.14, No.1 (2014) [Non-Patent Document 3] Chronic Inflammation and Schizophrenia, Molecular Psychiatry, Vol.14, No.1 (2014)
[非專利文獻4] Evidence-Based Complementary and Alternative Medicine, Vol.2015, Article ID 768049 (2015) [Non-Patent Document 4] Evidence-Based Complementary and Alternative Medicine, Vol.2015, Article ID 768049 (2015)
[非專利文獻5] Journal of Alzheimer’s Disease, 42, 587-605 (2014) [Non-Patent Document 5] Journal of Alzheimer’s Disease, 42, 587-605 (2014)
[非專利文獻6] Journal of Agricultural and Food Chemistry, 63, 3472-3480 (2015) [Non-Patent Document 6] Journal of Agricultural and Food Chemistry, 63, 3472-3480 (2015)
[非專利文獻7] 生化學，第85卷，第1號，p.1 (2013) [Non-Patent Document 7] Biochemistry, Vol. 85, No. 1, p. 1 (2013)
本發明之課題在於提供一種神經性疾病之預防用組成物、用以預防神經性疾病之素材的使用、及預防神經性疾病之方法。 An object of the present invention is to provide a composition for preventing a neurological disease, a method for preventing a neurological disease, and a method for preventing a neurological disease.
本案發明人等鑒於上述問題而致力進行研究的結果發現動植物性胜肽的熱處理物具有神經性疾病之預防效果。又，發現動植物性胜肽的熱處理物具有抑制由小神經膠質細胞分泌一氧化氮之效果，其結果，認定動植物性胜肽的熱處理物具有抑制小神經膠質細胞活化之作用及神經細胞之發炎抑制作用，終至完成本發明。 As a result of research conducted in view of the above problems, the inventors of the present invention found that the heat-treated product of the animal or plant peptide has a preventive effect against neurological diseases. Further, it has been found that a heat-treated product of an animal or plant peptide has an effect of inhibiting secretion of nitric oxide by microglia. As a result, it has been determined that a heat-treated substance of an animal or plant peptide has an action of inhibiting activation of microglia and inhibition of inflammation of nerve cells. The effect is to complete the present invention.
亦即，本發明係有關於以下者，但不限定於此。 That is, the present invention relates to the following, but is not limited thereto.
(1)一種神經性疾病之預防用組成物，其係含有動植物性胜肽熱處理物作為有效成分。 (1) A composition for preventing neurological diseases, which comprises a heat-treated product of an animal or plant peptide as an active ingredient.
(2)如(1)之神經性疾病之預防用組成物，其中動植物性胜肽熱處理物為動植物性胜肽的高溫高壓處理物。 (2) The composition for prevention of a neurological disease according to (1), wherein the heat-treated product of the animal or plant peptide is a high-temperature and high-pressure treated material of the animal or vegetable peptide.
(3)如(1)或(2)之神經性疾病之預防用組成物，其中高溫高壓處理物為以在100℃以上且0.101MPa以上之高溫高壓處理而得者。 (3) The composition for preventing neurological diseases according to (1) or (2), wherein the high-temperature and high-pressure treated material is obtained by treatment at a high temperature and high pressure of 100 ° C or more and 0.101 MPa or more.
(4)如(1)~(3)中任一項之神經性疾病之預防用組成物，其中動植物性胜肽為大豆胜肽或乳清胜肽。 (4) The preventive composition for a neurological disease according to any one of (1) to (3), wherein the animal or plant peptide is a soybean peptide or a whey peptide.
(5)如(1)~(4)中任一項之神經性疾病之預防 用組成物，其係具有神經細胞之發炎抑制作用。 (5) Prevention of a neurological disease according to any one of (1) to (4) The composition has an inflammatory inhibition effect of nerve cells.
(6)如(1)~(5)中任一項之神經性疾病之預防用組成物，其係具有抑制由小神經膠質細胞分泌一氧化氮之作用。 (6) The preventive composition for a neurological disease according to any one of (1) to (5), which has an effect of inhibiting secretion of nitric oxide by microglia.
(7)如(1)~(6)中任一項之神經性疾病之預防用組成物，其係具有抑制小神經膠質細胞活化之作用。 (7) The preventive composition for a neurological disease according to any one of (1) to (6), which has an action of inhibiting activation of microglia.
(8)如(1)~(7)中任一項之神經性疾病之預防用組成物，其係具有失智症之預防效果。 (8) The preventive composition for a neurological disease according to any one of (1) to (7), which has a preventive effect of dementia.
(9)如(1)~(7)中任一項之神經性疾病之預防用組成物，其係具有精神分裂症之預防效果。 (9) The preventive composition for a neurological disease according to any one of (1) to (7), which has a preventive effect against schizophrenia.
(10)如(1)~(7)中任一項之神經性疾病之預防用組成物，其係具有阿茲海默症之預防效果。 (10) The composition for preventing neurological diseases according to any one of (1) to (7), which has a prophylactic effect of Alzheimer's disease.
(11)如(1)~(7)中任一項之神經性疾病之預防用組成物，其係具有帕金森綜合症之預防效果。 (11) The preventive composition for a neurological disease according to any one of (1) to (7), which has a preventive effect of Parkinson's disease.
(12)如(1)~(7)中任一項之神經性疾病之預防用組成物，其係具有肌肉萎縮性脊髓側索硬化症之預防效果。 (12) The preventive composition for a neurological disease according to any one of (1) to (7), which has a preventive effect against amyotrophic lateral sclerosis.
(13)一種前述神經性疾病之預防用組成物，其係附有與神經性疾病之預防有關之機能之標示的如(1)~(12)中任一項之神經性疾病之預防用組成物， 機能之標示為選自由「降低神經性疾病之發病風險」、「降低失智症之發病風險」、「降低阿茲海默症之發病風險」、「降低帕金森綜合症之發病風險」、「降低精神分裂症之發病風險」、及「降低肌肉萎縮性脊髓側索 硬化症之發病風險」所成群組者。 (13) A preventive composition for a neurological disease according to any one of (1) to (12), which is characterized by a function related to the prevention of a neurological disease, Object, The function is marked by "reducing the risk of developing a neurological disease", "reducing the risk of dementia", "reducing the risk of developing Alzheimer's disease", "reducing the risk of Parkinson's disease", and "reducing the risk of Parkinson's disease" Reduce the risk of schizophrenia" and "reduce the muscle atrophic spinal cord The group of patients with the risk of sclerosing.
(14)一種動植物性胜肽熱處理物的使用，其係用以預防神經性疾病。 (14) Use of a heat-treated product of an animal or plant peptide for preventing a neurological disease.
(15)一種預防神經性疾病之方法，其係使用動植物性胜肽熱處理物作為有效成分。 (15) A method for preventing a neurological disease, which uses an animal-plant peptide heat-treated product as an active ingredient.
根據本發明，可提供一種具有神經性疾病之預防效果的組成物。由於本發明之組成物所含之動植物性胜肽熱處理物其安全性較高，本發明之組成物可謂市場上的利用價值極高。又，透過攝取本發明之組成物，可獲得抑制由小神經膠質細胞分泌一氧化氮之效果、抑制小神經膠質細胞活化之效果及神經細胞之發炎抑制效果等，藉此可發揮失智症預防效果、精神分裂症預防效果、阿茲海默症預防效果、帕金森綜合症預防效果、肌肉萎縮性脊髓側索硬化症預防效果等。 According to the present invention, a composition having a preventive effect against a neurological disease can be provided. Since the animal and vegetable peptide heat-treated product contained in the composition of the present invention has high safety, the composition of the present invention can be said to have extremely high use value in the market. Further, by ingesting the composition of the present invention, the effect of inhibiting secretion of nitric oxide by microglial cells, the effect of inhibiting activation of microglia, and the inhibitory effect of nerve cells can be obtained, thereby preventing dementia prevention. The effect, the preventive effect of schizophrenia, the preventive effect of Alzheimer's disease, the preventive effect of Parkinson's syndrome, and the preventive effect of amyotrophic lateral sclerosis.
第1圖係顯示在同時添加大豆胜肽熱處理物(最終濃度1mg/mL)及LPS(最終濃度100ng/mL)的條件下之由BV2小神經膠質細胞分泌之一氧化氮代謝物的產生量(將添加蒸餾水之群的產生量設為100時的NO2 -產生量)。 Figure 1 shows the amount of nitric oxide metabolites secreted by BV2 microglial cells under conditions of simultaneous addition of a heat-treated soybean peptide (final concentration of 1 mg/mL) and LPS (final concentration of 100 ng/mL). The amount of NO 2 - produced when the amount of the distilled water added was set to 100).
第2圖係顯示在同時添加大豆胜肽熱處理物(最終濃 度5mg/mL)及LPS(最終濃度100ng/mL)的條件下之由BV2小神經膠質細胞分泌之一氧化氮代謝物的產生量(將添加蒸餾水之群的產生量設為100時的NO2 -產生量)。 Figure 2 shows the amount of nitric oxide metabolites secreted by BV2 microglial cells under conditions of simultaneous addition of a heat-treated soybean peptide (final concentration of 5 mg/mL) and LPS (final concentration of 100 ng/mL). The amount of NO 2 - produced when the amount of the distilled water added was set to 100).
第3圖係顯示在同時添加乳清胜肽熱處理物(最終濃度1mg/mL)及LPS(最終濃度100ng/mL)的條件下之由BV2小神經膠質細胞分泌之一氧化氮代謝物的產生量(將添加蒸餾水之群的產生量設為100時的NO2 -產生量)。 Figure 3 shows the amount of nitric oxide metabolites secreted by BV2 microglial cells under conditions of simultaneous addition of whey peptide heat treatment (final concentration 1 mg/mL) and LPS (final concentration 100 ng/mL). (The amount of NO 2 - produced when the amount of the distilled water added was set to 100).
第4圖係顯示在同時添加乳清胜肽熱處理物(最終濃度5mg/mL)及LPS(最終濃度100ng/mL)的條件下之由BV2小神經膠質細胞分泌之一氧化氮代謝物的產生量(將添加蒸餾水之群的產生量設為100時的NO2 -產生量)。 Figure 4 shows the amount of nitric oxide metabolites secreted by BV2 microglial cells under conditions of simultaneous addition of whey peptide heat treatment (final concentration 5 mg/mL) and LPS (final concentration 100 ng/mL). (The amount of NO 2 - produced when the amount of the distilled water added was set to 100).
本發明一形態為一種含有動植物性胜肽熱處理物作為有效成分的神經性疾病之預防用組成物。 One aspect of the present invention provides a composition for preventing neurological diseases comprising a heat-treated product of an animal or plant peptide as an active ingredient.
本說明書中「動植物性胜肽」可為動物性胜肽或植物性胜肽。本說明書中「動物性胜肽」，若非特別合先敘明，則意指藉由對來自動物之蛋白質或含蛋白質的動物體 實施已知之分解處理(藉由熱或壓力之分解處理、藉由酸或鹼之分解處理、藉由酵素之分解處理等)予以低分子化而生成的胜肽。又，本說明書中「植物性胜肽」，若非特別合先敘明，則意指藉由對來自植物之蛋白質或含蛋白質的植物體實施已知之分解處理(藉由熱或壓力之分解處理、藉由酸或鹼之分解處理、藉由酵素之分解處理等)予以低分子化而生成的胜肽。此外，本說明書中「動植物」係包含「動物」及「植物」。 In the present specification, "animal or vegetable peptide" may be an animal peptide or a vegetable peptide. In the present specification, "animal peptide", unless specifically stated in the specification, means by using an animal-derived protein or a protein-containing animal body. A known peptide decomposition treatment (decomposition treatment by heat or pressure, decomposition treatment by acid or alkali, decomposition treatment by an enzyme, etc.) is carried out to obtain a peptide which is produced by lowering the molecular weight. In addition, in the present specification, "plant-derived peptide", unless otherwise specified, means that a plant-derived protein or a protein-containing plant body is subjected to a known decomposition treatment (by heat or pressure decomposition treatment, A peptide produced by decomposing a molecule by decomposition treatment of an acid or a base, decomposition treatment by an enzyme, or the like. In addition, "animals and plants" in this specification include "animals" and "plants".
本發明之動植物性胜肽可為由來自動植物之蛋白質或含蛋白質的動植物體取得的1種胜肽，也可為2種以上之胜肽的混合物。構成動植物性胜肽的胺基酸個數不特別限定，較佳為2~數十個，更佳為2~數個(即寡肽)。 The animal or plant peptide of the present invention may be one peptide obtained from a protein of an automatic plant or a plant or animal containing protein, or a mixture of two or more peptides. The number of amino acids constituting the phytophytic peptide is not particularly limited, but is preferably 2 to several tens, more preferably 2 to several (i.e., oligopeptide).
本發明中，動植物性胜肽較佳使用分子量5000以下之胜肽的比例較高者，更佳使用分子量3000以下之胜肽的比例較高者，特佳使用分子量1000以下之胜肽的比例較高者。於此，所稱「胜肽的比例較高」，係指動植物性胜肽全體的至少50%屬於該胜肽的狀態。該分子量的測定可利用本領域具有通常知識者所熟知的方法及裝置(HPLC等)來進行。 In the present invention, the ratio of the peptide having a molecular weight of 5,000 or less is preferably higher, and the ratio of the peptide having a molecular weight of 3,000 or less is higher, and the ratio of the peptide having a molecular weight of 1,000 or less is preferably used. The taller. Here, the term "higher ratio of peptide" means that at least 50% of the entire animal and vegetable peptides belong to the peptide. The measurement of the molecular weight can be carried out by a method and apparatus (HPLC, etc.) well known to those skilled in the art.
本發明之動植物性胜肽不特別限定，可適宜利用豆類、種子類、芋類等來自植物之胜肽；或乳清、胎盤、膠原蛋白等來自動物之胜肽。作為豆類，可舉出例如大豆、紅豆、黑豆等。作為種子類，可舉出例如大麥、小麥(含小麥胚芽)、麥芽、芝麻、米等。作為芋類，可舉出例如 番薯、馬鈴薯等。此等當中，於本發明中較佳為大豆及乳清。此外，於本說明書中，就來自於特定之動植物的動植物性胜肽，有時省略「來自」之記載。例如，若為「來自大豆之胜肽」時，有時將其稱為「大豆胜肽」。此時，係兩者可互換地使用。 The animal or plant peptide of the present invention is not particularly limited, and a peptide derived from plants such as beans, seeds, and mites may be suitably used; or a peptide derived from an animal such as whey, placenta, or collagen. Examples of the beans include soybeans, red beans, black beans, and the like. Examples of the seed include barley, wheat (including wheat germ), malt, sesame, rice, and the like. As the hydrazine, for example, Sweet potato, potato, etc. Among these, soybean and whey are preferred in the present invention. In addition, in this specification, the animal-plant peptide derived from a specific animal or plant may be omitted from the description of "from". For example, in the case of "the peptide derived from soybean", it is sometimes referred to as "soybean peptide". At this time, the two are used interchangeably.
動植物性胜肽可藉由將來自動植物之蛋白質或含蛋白質的動植物體以向來周知之方法進行分解處理而得。作為所述分解處理，可舉出藉由熱或壓力之分解處理、藉由酸或鹼之分解處理、藉由酵素之分解處理等。在任一種處理中，皆可使用水或乙醇等作為溶媒，若為例如藉由加熱之分解處理，可例示100℃以上的溫度、30分~數小時之條件。此外，此加熱處理亦可與上述之動植物性胜肽熱處理物的加熱處理同時進行。又，若為藉由酵素之分解處理，則可視其目的適宜使用各種的蛋白質分解酵素(蛋白酶)。 The animal or plant peptide can be obtained by decomposing a protein of a plant or a protein-containing animal or plant in the future by a well-known method. Examples of the decomposition treatment include decomposition treatment by heat or pressure, decomposition treatment by acid or alkali, decomposition treatment by an enzyme, and the like. In any of the treatments, water or ethanol or the like can be used as the solvent, and for example, by decomposition treatment by heating, a temperature of 100 ° C or higher and a condition of 30 minutes to several hours can be exemplified. Further, this heat treatment may be carried out simultaneously with the heat treatment of the above-described heat treatment product for animal and plant peptides. Further, in the case of decomposition treatment by an enzyme, various proteolytic enzymes (protease) can be suitably used depending on the purpose.
動植物性胜肽可使用採用周知之方法自行調製者，亦可使用市售品。作為市售之植物性胜肽，可舉出例如HINUTE AM、HINUTE DC、HINUTE HK(以上為不二製油公司製)等的大豆胜肽、ORYZA PEPTIDE-P60(Oryza Oil&Fat Chemical公司製)等的米胜肽、GLUTAMINE PEPTIDE GP-1N、GLUTAMINE PEPTIDE GP-N(以上為Nisshin Pharma公司製)等的小麥胜肽、Sesame peptide KM-20(KISCO公司製)等的芝麻胜肽。作為市售之動物性胜肽，可舉出例如Whey Peptide HW-3(MEGMILK SNOW BRAND公司製)、Whey Peptide Peptigen IF-3090(Arla Foods公司製)等的乳清胜肽、森永乳業公司製之Casein Peptide CU2500A、Health-support公司製之胎盤胜肽、Nitta Gelatin公司製之膠原胜肽等。 The animal or vegetable peptide can be prepared by a known method, and a commercially available product can also be used. For example, a soybean peptide such as HINUTE AM, HINUTE DC, HINUTE HK (manufactured by Fuji Oil Co., Ltd.), or ORYZA PEPTIDE-P60 (manufactured by Oryza Oil & Fat Chemical Co., Ltd.), etc., may be mentioned. A sesame peptide such as a peptide, a GLUTAMINE PEPTIDE GP-1N, a GLUTAMINE PEPTIDE GP-N (above, Nisshin Pharma), or a Sesame peptide KM-20 (manufactured by KISCO). As a commercially available animal peptide, for example, Whey Peptide HW-3 (MEGMILK) Whey peptides made by SNOW BRAND, Whey Peptide Peptigen IF-3090 (manufactured by Arla Foods), Casein Peptide CU2500A manufactured by Morinaga Dairy Co., Ltd., placenta peptides manufactured by Health-support, and collagens manufactured by Nitta Gelatin Peptide and so on.
動植物性胜肽熱處理物可藉由將動植物性胜肽在液體中進行高溫加熱處理而得。該高溫加熱處理不特別限定，較佳的是除高溫條件外，再加上高壓條件之條件下的處理。作為高溫加熱處理及高溫高壓處理中的液體，可適合使用純水，惟亦可使其適宜含有乙醇等有機溶媒。又，亦可藉由對萃取溶媒添加礦物質分來適宜調整硬度。 The heat treatment of the animal and plant peptides can be obtained by subjecting the animal and plant peptides to high temperature heat treatment in a liquid. The high-temperature heat treatment is not particularly limited, and it is preferably a treatment under conditions of high pressure conditions in addition to high-temperature conditions. As the liquid in the high-temperature heat treatment and the high-temperature high-pressure treatment, pure water can be suitably used, but it is also preferable to contain an organic solvent such as ethanol. Further, the hardness can be appropriately adjusted by adding a mineral component to the extraction solvent.
本說明書中所稱「高溫加熱處理」，係指在100℃以上的溫度且超過大氣壓的壓力下進行一定時間的處理之意。作為高溫高壓處理裝置，可配合條件使用耐壓性萃取裝置或壓力鍋、高壓釜等。 The term "high-temperature heat treatment" as used in the present specification means a treatment performed at a temperature of 100 ° C or higher and a pressure exceeding atmospheric pressure for a certain period of time. As the high-temperature high-pressure treatment device, a pressure-resistant extraction device, a pressure cooker, an autoclave or the like can be used in accordance with the conditions.
高溫加熱處理中的溫度，只要是100℃以上則不特別限定，較佳為105℃以上、110℃以上、115℃以上、120℃以上、125℃以上、130℃以上、或135℃以上。又，該溫度較佳為170℃以下、165℃以下、160℃以下、155℃以下、150℃以下、145℃以下、或140℃以下。典型上，該溫度為100℃~170℃，較佳為110℃~150℃，更佳為120℃~140℃。此外，以此溫度而言，在使用耐壓性萃取裝置作為加熱裝置時，係表示測定萃取管柱的出口溫度所 得的值；在使用高壓釜作為加熱裝置時，則表示測定壓力容器內之中心溫度的溫度所得的值。 The temperature in the high-temperature heat treatment is not particularly limited as long as it is 100° C. or more, and is preferably 105° C. or higher, 110° C. or higher, 115° C. or higher, 120° C. or higher, 125° C. or higher, 130° C. or higher, or 135° C. or higher. Further, the temperature is preferably 170 ° C or less, 165 ° C or less, 160 ° C or less, 155 ° C or less, 150 ° C or less, 145 ° C or less, or 140 ° C or less. Typically, the temperature is from 100 ° C to 170 ° C, preferably from 110 ° C to 150 ° C, more preferably from 120 ° C to 140 ° C. Further, in terms of this temperature, when the pressure-resistant extraction device is used as the heating device, it means that the outlet temperature of the extraction column is measured. The value obtained is a value obtained by measuring the temperature of the center temperature in the pressure vessel when the autoclave is used as the heating device.
高溫高壓的壓力，只要是超過大氣壓的壓力則不特別限定，較佳為0.101MPa以上、0.15MPa以上、0.2MPa以上、0.25MPa以上、或0.3MPa以上。又，該壓力較佳為0.79MPa以下、0.75MPa以下、0.7MPa以下、0.65MPa以下、0.6MPa以下、0.55MPa以下、0.5MPa以下、0.48MPa以下。典型上，該壓力為0.101MPa~0.79MPa，較佳為0.101MPa~0.60MPa，更佳為0.101MPa~0.48MPa。 The high-temperature high-pressure pressure is not particularly limited as long as it is a pressure exceeding atmospheric pressure, and is preferably 0.101 MPa or more, 0.15 MPa or more, 0.2 MPa or more, 0.25 MPa or more, or 0.3 MPa or more. Further, the pressure is preferably 0.79 MPa or less, 0.75 MPa or less, 0.7 MPa or less, 0.65 MPa or less, 0.6 MPa or less, 0.55 MPa or less, 0.5 MPa or less, or 0.48 MPa or less. Typically, the pressure is from 0.101 MPa to 0.79 MPa, preferably from 0.101 MPa to 0.60 MPa, more preferably from 0.101 MPa to 0.48 MPa.
高溫加熱處理時間，只要可獲得所期望的處理物則不特別限定，較佳為15分~600分左右，更佳為30分~500分左右，再更佳為60分~300分左右。 The high-temperature heat treatment time is not particularly limited as long as the desired treatment product can be obtained, and is preferably about 15 minutes to 600 minutes, more preferably about 30 minutes to 500 minutes, and even more preferably about 60 minutes to 300 minutes.
本發明中用於獲得動植物性胜肽熱處理物的更適合的高溫處理條件，係例如在將橫軸設為時間(min.)、將縱軸設為溫度(℃)的座標系中，在由以下座標系(i)~(vi)所包圍之時間及溫度的範圍內保持的高溫處理：(i)(170℃，30min.)、(ii)(150℃，30min.)、(iii)(115℃，180min.)、(iv)(105℃，480min.)、(v)(135℃，480min.)、(vi)(150℃，180min.)。 In the present invention, more suitable high-temperature treatment conditions for obtaining a heat-treated product of an animal or plant peptide are, for example, in a coordinate system in which the horizontal axis is time (min.) and the vertical axis is temperature (°C). The following coordinates are the high temperature treatments maintained during the time and temperature range enclosed by (i) to (vi): (i) (170 ° C, 30 min.), (ii) (150 ° C, 30 min.), (iii) ( 115 ° C, 180 min.), (iv) (105 ° C, 480 min.), (v) (135 ° C, 480 min.), (vi) (150 ° C, 180 min.).
與用於獲得動植物性胜肽熱處理物之動植物性胜肽的溫度、壓力及時間有關的處理條件不特別限定，例如可如下設定： (溫度、壓力、時間)=(105℃~170℃、0.101MPa~0.79MPa、15分~600分)、(105℃~170℃、0.101MPa~0.79MPa、30分~500分)、(105℃~170℃、0.101MPa~0.79MPa、60分~300分)、(105℃~170℃、0.15MPa~0.48MPa、15分~600分)、(105℃~170℃、0.15MPa~0.48MPa、30分~500分)、(105℃~170℃、0.15MPa~0.48MPa、60分~300分)、(110℃~150℃、0.101MPa~0.79MPa、15分~600分)、(110℃~150℃、0.101MPa~0.79MPa、30分~500分)、(110℃~150℃、0.101MPa~0.79MPa、60分~300分)、(110℃~150℃、0.15MPa~0.48MPa、15分~600分)、(110℃~150℃、0.15MPa~0.48MPa、30分~500分)、(110℃~150℃、0.15MPa~0.48MPa、60分~300分)、(120℃~140℃、0.101MPa~0.79MPa、15分~600分)、(120℃~140℃、0.101MPa~0.79MPa、30分~500分)、(120℃~140℃、0.101MPa~0.79MPa、60分~300分)、(120℃~140℃、0.15MPa~0.48MPa、15分~600分)、(120℃~140℃、0.15MPa~0.48MPa、30分~500分)、(120℃~140℃、0.15MPa~0.48MPa、60分~300分)等。 The processing conditions relating to the temperature, pressure, and time of the animal or vegetable peptide for obtaining the heat-treated animal of the animal or plant peptide are not particularly limited, and can be set, for example, as follows: (temperature, pressure, time) = (105 ° C ~ 170 ° C, 0.101 MPa ~ 0.79 MPa, 15 minutes ~ 600 minutes), (105 ° C ~ 170 ° C, 0.101 MPa ~ 0.79 MPa, 30 minutes ~ 500 points), (105 °C~170°C, 0.101MPa~0.79MPa, 60 minutes~300 minutes), (105°C~170°C, 0.15MPa~0.48MPa, 15 minutes~600 minutes), (105°C~170°C, 0.15MPa~0.48MPa) 30 minutes to 500 minutes), (105°C to 170°C, 0.15MPa to 0.48MPa, 60 minutes to 300 minutes), (110°C to 150°C, 0.101MPa to 0.79MPa, 15 minutes to 600 minutes), (110) °C~150°C, 0.101MPa~0.79MPa, 30 minutes~500 points), (110°C~150°C, 0.101MPa~0.79MPa, 60 minutes~300 minutes), (110°C~150°C, 0.15MPa~0.48MPa) , 15 minutes to 600 minutes), (110 ° C ~ 150 ° C, 0.15 MPa ~ 0.48 MPa, 30 minutes ~ 500 points), (110 ° C ~ 150 ° C, 0.15 MPa ~ 0.48 MPa, 60 minutes ~ 300 points), (120 °C~140°C, 0.101MPa~0.79MPa, 15 minutes~600 minutes), (120°C~140°C, 0.101MPa~0.79MPa, 30 minutes~500 points), (120°C~140°C, 0.101MPa~0.79MPa) , 60 minutes to 300 minutes), (120 ° C ~ 140 ° C, 0.15 MPa ~ 0.48 MPa, 15 minutes ~ 600 points), (120 ° C ~ 140 ° C, 0.15 MPa ~ 0.48 MPa, 30 minutes ~ 500 points), (120 °C~140°C, 0.15MPa~0.48MPa, 60 minutes~300 points).
本發明中動植物性胜肽熱處理物可使用可提供上述之處理條件的裝置來調製。作為此種裝置，可舉出例如本領域具有通常知識者所熟知的耐壓性萃取裝置、壓力鍋及高壓釜等，但不特別限定於此等。又，動植物性胜肽熱處理物亦可於加熱處理前及/或後進行過固液分離。藉由進行 固液分離之處理，可回收液體部分，而能夠僅以固體來取用。固液分離可使用濾液及/或離心分離等的手段。又，動植物性胜肽熱處理物亦可於加熱處理後進一步實施過精製處理。藉由進行精製處理，可濃縮動植物性胜肽熱處理物所含的特定成分。動植物性胜肽熱處理物的精製處理可利用周知之方法及裝置來進行。再者，動植物性胜肽熱處理物亦可於加熱處理前及/或後進一步進行過澄清化處理。澄清化處理可利用周知之方法及裝置來進行，透過該處理可增大添加動植物性胜肽熱處理物的組成物的設計自由度。又，動植物性胜肽熱處理物亦可利用周知之方法及裝置進行過冷凍乾燥或粉末化。另外，本發明中的動植物性胜肽熱處理物之製造方法能以國際公開第2014/200000號所記載的方法為參考。 The heat treatment of the animal or plant peptide in the present invention can be prepared using a device which provides the above-described processing conditions. Examples of such a device include, but are not limited to, a pressure-resistant extraction device, a pressure cooker, and an autoclave which are well known to those skilled in the art. Further, the heat treatment product of the animal or plant peptide may be subjected to solid-liquid separation before and/or after the heat treatment. By doing The solid-liquid separation treatment can recover the liquid portion and can be taken only as a solid. For solid-liquid separation, a means such as a filtrate and/or centrifugation can be used. Further, the heat treatment product of the animal or plant peptide may be further subjected to a refining treatment after the heat treatment. By performing the refining treatment, the specific component contained in the heat-treated product of the animal and vegetable peptide can be concentrated. The refining treatment of the heat-treated animal or vegetable peptide can be carried out by a known method and apparatus. Further, the heat treatment product of the animal or plant peptide may be further subjected to clarification treatment before and/or after the heat treatment. The clarification treatment can be carried out by a known method and apparatus, and the degree of freedom in designing the composition of the heat-treated product of the animal or plant peptide can be increased by this treatment. Further, the heat treatment product of the animal or plant peptide can also be freeze-dried or powdered by a known method and apparatus. Further, the method for producing a heat-treated animal of plant and animal peptides in the present invention can be referred to the method described in International Publication No. 2014/200000.
動植物性胜肽熱處理物可藉由將動植物性胜肽進行高溫加熱處理或高溫高壓處理而得，透過該處理，大量的環狀二肽或其鹽即含於動植物性胜肽熱處理物中。亦即，本發明中動植物性胜肽熱處理物，其特徵之一為含有環狀二肽或其鹽。較理想為不受特定的理論所侷限，而動植物性胜肽熱處理物中由於含有大量的環狀二肽或其鹽，該環狀二肽或其鹽可作為神經性疾病之預防用組成物的有效成分。此外，於本說明書中，有將環狀二肽或其鹽一併單稱為環狀二肽。 The heat treatment product of the animal or vegetable peptide can be obtained by subjecting the animal or vegetable peptide to high temperature heat treatment or high temperature and high pressure treatment, and a large amount of the cyclic dipeptide or a salt thereof is contained in the heat treatment of the animal and plant peptide by the treatment. That is, one of the characteristics of the heat-treated animal or plant peptide in the present invention is that it contains a cyclic dipeptide or a salt thereof. It is preferable that it is not limited by a specific theory, and since the heat treatment of the animal or plant peptide is contained in a large amount of a cyclic dipeptide or a salt thereof, the cyclic dipeptide or a salt thereof can be used as a preventive component of a neurological disease. Active ingredients. Further, in the present specification, the cyclic dipeptide or a salt thereof is collectively referred to as a cyclic dipeptide.
本說明書中所稱環狀二肽，係指特徵為以胺基酸為構成單位，且具有胺基酸的胺基與羧基經脫水縮合而生成的二酮哌嗪結構之二肽。因此，環狀二肽係有別於直鏈狀的二肽。 The term "cyclic dipeptide" as used herein refers to a diketopiperazine structure dipeptide which is characterized by having an amino acid as a constituent unit and having an amino group of an amino acid and a carboxyl group formed by dehydration condensation. Therefore, the cyclic dipeptide system is different from the linear dipeptide.
環狀二肽的鹽係包含藥理學上可容許的任意的鹽(包含無機鹽及有機鹽)。作為此種鹽，可舉出例如鈉鹽、鉀鹽、鈣鹽、鎂鹽、銨鹽、鹽酸鹽、硫酸鹽、硝酸鹽、磷酸鹽、有機酸鹽(乙酸鹽、檸檬酸鹽、馬來酸鹽、蘋果酸鹽、草酸鹽、乳酸鹽、琥珀酸鹽、富馬酸鹽、丙酸鹽、甲酸鹽、苯甲酸鹽、苦味酸鹽、苯磺酸鹽、三氟乙酸鹽等)等，但不限定於此等。 The salt of the cyclic dipeptide includes any salt (including inorganic salts and organic salts) which is pharmacologically acceptable. Examples of such a salt include a sodium salt, a potassium salt, a calcium salt, a magnesium salt, an ammonium salt, a hydrochloride, a sulfate, a nitrate, a phosphate, and an organic acid salt (acetate, citrate, and Malay). Acid salts, malate, oxalate, lactate, succinate, fumarate, propionate, formate, benzoate, picrate, besylate, trifluoroacetate, etc. ), etc., but not limited to this.
動植物性胜肽熱處理物所含之環狀二肽或其鹽的量係隨動植物性胜肽熱處理物的種類等而異，不特別限定；例如，動植物性胜肽熱處理物中每單位布里克氏(Brix)之環狀二肽或其鹽的總量較佳為20000μg/100g/Bx以上、25000μg/100g/Bx以上、30000μg/100g/Bx以上，更佳為35000μg/100g/Bx以上。又，該總量較佳為10000mg/100g/Bx以下、5000mg/100g/Bx以下、2000mg/100g/Bx以下，更佳為1000mg/100g/Bx以下。典型上，本發明中的動植物性胜肽熱處理物所含之環狀二肽或其鹽的總量較佳為20000μg/100g/Bx~10000mg/100g/Bx，更佳為30000μg/100g/Bx~5000mg/100g/Bx，再更佳為35000μg/100g/Bx~1000mg/100g/Bx。 The amount of the cyclic dipeptide or the salt thereof contained in the heat-treated product of the animal or plant peptide varies depending on the kind of the heat-treated product of the animal or plant peptide, and is not particularly limited; for example, the heat of the animal and plant peptides per unit of Brick The total amount of the cyclic dipeptide or a salt thereof of Brix is preferably 20,000 μg/100 g/Bx or more, 25,000 μg/100 g/Bx or more, 30,000 μg/100 g/Bx or more, and more preferably 35,000 μg/100 g/Bx or more. Further, the total amount is preferably 10000 mg/100 g/Bx or less, 5000 mg/100 g/Bx or less, 2000 mg/100 g/Bx or less, more preferably 1000 mg/100 g/Bx or less. Typically, the total amount of the cyclic dipeptide or a salt thereof contained in the heat-treated animal or vegetable peptide of the present invention is preferably 20,000 μg / 100 g / Bx - 10000 mg / 100 g / Bx, more preferably 30,000 μg / 100 g / Bx ~ 5000 mg / 100 g / Bx, more preferably 35000 μg / 100g / Bx ~ 1000mg / 100g / Bx.
當環狀二肽為鹽的形態時，係換算為游離體(自由 體)後再算出上述含量。 When the cyclic dipeptide is in the form of a salt, it is converted into a free form (free After the body), the above content was calculated.
作為本發明中之動植物性胜肽熱處理物的較佳形態，可例示麥芽胜肽熱處理物及乳清胜肽熱處理物。以下，就此等熱處理物中的環狀二肽詳細加以敘述。 A preferred embodiment of the heat-treated animal of the animal or plant peptide in the present invention is a heat-treated product of malt peptide and a heat-treated product of whey peptide. Hereinafter, the cyclic dipeptide in these heat treatments will be described in detail.
作為原料的大豆(學名：Glycine max)可不限品種或產地等地使用，亦可使用粉碎品等的加工品階段者。大豆中的蛋白質一般而言占約3成。由於大豆蛋白質不若茶葉蛋白質般有較多的水不溶性蛋白質，因此不需要去除水溶性蛋白質的前處理，只要視需求進行即可。若無去除水溶性蛋白質的前處理時，則能以一鍋化(One-Pot)反應更簡便地製造含有高濃度環狀二肽的大豆胜肽熱處理物。 Soybean (scientific name: Glycine max) which is a raw material can be used in an unlimited number of varieties or places of production, and a processed product stage such as a pulverized product can also be used. The protein in soybeans generally accounts for about 30%. Since soybean protein does not have many water-insoluble proteins like tea protein, it is not necessary to remove the pretreatment of water-soluble protein, and it is only necessary to carry out it as needed. If the pretreatment of the water-soluble protein is not removed, the heat treatment of the soybean peptide containing the high concentration of the cyclic dipeptide can be more easily produced by the One-Pot reaction.
本發明中的大豆胜肽熱處理物係以每單位Bx的含量為10μg/100g/Bx以上含有未含於以往的大豆蛋白分解物(大豆胜肽)之屬環狀二肽的Cyclo(Ala-Gln)、Cyclo(Ala-Ala)、Cyclo(Ser-Tyr)、Cyclo(Gly-Trp)、Cyclo(Val-Val)、Cyclo(Trp-Tyr)、Cyclo(Leu-Trp)及Cyclo(Phe-Phe)的任一種以上。 The soybean peptide heat treatment product of the present invention contains Cyclo (Ala-Gln) which is a cyclic dipeptide which is not contained in the conventional soybean protein degradation product (soy peptide) at a Bx content of 10 μg/100 g/Bx or more per unit. ), Cyclo (Ala-Ala), Cyclo (Ser-Tyr), Cyclo (Gly-Trp), Cyclo (Val-Val), Cyclo (Trp-Tyr), Cyclo (Leu-Trp), and Cyclo (Phe-Phe) Any one or more.
又，本發明中的大豆胜肽熱處理物係分別以0.1ppm/Bx(10μg/100g/Bx)以上的濃度含有Cyclo(Ala-Gln)、Cyclo(His-Pro)、Cyclo(Ala-Ala)、Cyclo(Gly-Pro)、Cyclo(Ser-Tyr)、Cyclo(Pro-Thr)、Cyclo(His-Phe)、Cyclo(Ala-Pro)、Cyclo(Phe- Ser)、Cyclo(Gly-Leu)、Cyclo(Gly-Phe)、Cyclo(Gly-Trp)、Cyclo(Asp-Phe)、Cyclo(Val-Pro)、Cyclo(Pro-Tyr)、Cyclo(Met-Pro)、Cyclo(Val-Val)、Cyclo(Leu-Pro)、Cyclo(Trp-Tyr)、Cyclo(Phe-Pro)、Cyclo(Leu-Trp)、Cyclo(Leu-Phe)、Cyclo(Leu-Leu)及Cyclo(Phe-Phe)。較佳為以0.5ppm/Bx以上，更佳為0.7ppm/Bx以上，再更佳為0.9ppm/Bx以上，特佳為1.0ppm/Bx以上，特佳為1.2ppm/Bx以上的濃度含有上述之環狀二肽各者的大豆胜肽熱處理物。再者，可分別以0.1ppm/Bx(10μg/100g/Bx)以上，較佳為0.2ppm/Bx以上，更佳為0.3ppm/Bx以上的濃度使其含有Cyclo(Leu-Leu)、Cyclo(Leu-Phe)、Cyclo(Ser-Tyr)及Cyclo(Pro-Thr)。 Further, the soybean peptide heat treatment product of the present invention contains Cyclo (Ala-Gln), Cyclo (His-Pro), Cyclo (Ala-Ala), respectively, at a concentration of 0.1 ppm/Bx (10 μg/100 g/Bx) or more. Cyclo (Gly-Pro), Cyclo (Ser-Tyr), Cyclo (Pro-Thr), Cyclo (His-Phe), Cyclo (Ala-Pro), Cyclo (Phe- Ser), Cyclo (Gly-Leu), Cyclo (Gly-Phe), Cyclo (Gly-Trp), Cyclo (Asp-Phe), Cyclo (Val-Pro), Cyclo (Pro-Tyr), Cyclo (Met-Pro) ), Cyclo (Val-Val), Cyclo (Leu-Pro), Cyclo (Trp-Tyr), Cyclo (Phe-Pro), Cyclo (Leu-Trp), Cyclo (Leu-Phe), Cyclo (Leu-Leu) And Cyclo (Phe-Phe). It is preferably 0.5 ppm/Bx or more, more preferably 0.7 ppm/Bx or more, still more preferably 0.9 ppm/Bx or more, particularly preferably 1.0 ppm/Bx or more, and particularly preferably 1.2 ppm/Bx or more. A heat treatment of a soybean peptide of each of the cyclic dipeptides. Further, it may be contained in a concentration of 0.1 ppm/Bx (10 μg/100 g/Bx) or more, preferably 0.2 ppm/Bx or more, more preferably 0.3 ppm/Bx or more, in a concentration of Cyclo (Leu-Leu) or Cyclo ( Leu-Phe), Cyclo (Ser-Tyr) and Cyclo (Pro-Thr).
此大豆胜肽熱處理物(尤為以大豆或其粉碎物為原料而得的熱處理物)儘管含有已知為苦味較強之環狀二肽的Cyclo(Leu-Pro)、Cyclo(Phe-Pro)及Cyclo(Leu-Trp)，但仍可降低其苦味。調製含有相同濃度的Cyclo(Leu-Pro)及Cyclo(Phe-Pro)之水溶液時，由於會感到較強的苦味，茲認為共存的其他環狀二肽或來自大豆之成分會相加或相乘性地緩和Cyclo(Leu-Pro)、及Cyclo(Phe-Pro)及Cyclo(Leu-Trp)的苦味。特別是，具苦味之環狀二肽Cyclo(Leu-Pro)、Cyclo(Phe-Pro)及Cyclo(Leu-Trp)的總量(B)相對於Cyclo(Leu-Leu)與Cyclo(Leu-Phe)的總量(A)之比例〔(B)/ (A)〕為1.0以下(較佳為0.8以下，更佳為0.6以下，特佳為0.5以下)的大豆胜肽熱處理物為苦味經顯著降低的含環狀二肽之熱處理物，可口服施用之。 The heat-treated product of the soybean peptide (especially a heat-treated product obtained from soybean or a pulverized material thereof) contains Cyclo (Leu-Pro), Cyclo (Phe-Pro) and a cyclic dipeptide which is known to have a strong bitter taste. Cyclo (Leu-Trp), but still reduce its bitterness. When preparing an aqueous solution containing Cyclo (Leu-Pro) and Cyclo (Phe-Pro) at the same concentration, it is considered that a strong bitter taste is felt, and it is considered that other co-existing cyclic dipeptides or components derived from soybeans may be added or multiplied. Slightly moderate the bitterness of Cyclo (Leu-Pro), Cyclo (Phe-Pro) and Cyclo (Leu-Trp). In particular, the total amount of the bitter cyclic dipeptides Cyclo (Leu-Pro), Cyclo (Phe-Pro), and Cyclo (Leu-Trp) (B) relative to Cyclo (Leu-Leu) and Cyclo (Leu-Phe) The ratio of the total amount (A) [(B)/ (A) is a heat-treated product of a soybean peptide having a significantly reduced bitterness, which is 1.0 or less (preferably 0.8 or less, more preferably 0.6 or less, and particularly preferably 0.5 or less), and can be orally administered. It.
本發明之大豆胜肽熱處理物中每單位Bx之環狀二肽或其鹽的總量較佳為20000μg/100g/Bx以上、25000μg/100g/Bx以上、30000μg/100g/Bx以上，更佳為35000μg/100g/Bx以上。又，該總量較佳為10000mg/100g/Bx以下、5000mg/100g/Bx以下、2000mg/100g/Bx以下，更佳為1000mg/100g/Bx以下。典型上，本發明之大豆胜肽熱處理物中每單位Bx之環狀二肽或其鹽的總量較佳為20000μg/100g/Bx~10000mg/100g/Bx，更佳為30000μg/100g/Bx~5000mg/100g/Bx，再更佳為35000μg/100g/Bx~1000mg/100g/Bx。 The total amount of the cyclic dipeptide per unit Bx or a salt thereof in the heat treatment of the soybean peptide of the present invention is preferably 20,000 μg/100 g/Bx or more, 25,000 μg/100 g/Bx or more, and 30,000 μg/100 g/Bx or more, more preferably 35000 μg / 100 g / Bx or more. Further, the total amount is preferably 10000 mg/100 g/Bx or less, 5000 mg/100 g/Bx or less, 2000 mg/100 g/Bx or less, more preferably 1000 mg/100 g/Bx or less. Typically, the total amount of the cyclic dipeptide per unit Bx or a salt thereof in the heat treatment of the soybean peptide of the present invention is preferably 20,000 μg / 100 g / Bx - 10000 mg / 100 g / Bx, more preferably 30,000 μg / 100 g / Bx ~ 5000 mg / 100 g / Bx, more preferably 35000 μg / 100g / Bx ~ 1000mg / 100g / Bx.
本發明之大豆胜肽熱處理物較佳以高濃度含有Cyclo(Leu-Leu)、Cyclo(Leu-Phe)、Cyclo(Ser-Tyr)及Cyclo(Pro-Thr)。具體而言，相對於大豆胜肽熱處理物中的環狀二肽總量，Cyclo(Leu-Leu)為8%以上(重量基準)、Cyclo(Leu-Phe)為8%以上、Cyclo(Ser-Tyr)為6%以上的熱處理物。大豆胜肽熱處理物中，此等的濃度分別為0.1ppm/Bx(10μg/100g/Bx)，較佳為5.0ppm/Bx以上，更佳為6.0ppm/Bx以上，再更佳為7.0ppm/Bx以上。特佳的是Cyclo(Leu-Leu)及Cyclo(Leu-Phe)的含量為10.0ppm/Bx以上，較佳為12.0ppm/Bx以上。此等的上限不特別限定，較佳為 500ppm/Bx以下、400ppm/Bx以下，更佳為350ppm/Bx以下，再更佳為300ppm/Bx以下左右。 The heat treatment product of the soybean peptide of the present invention preferably contains Cyclo (Leu-Leu), Cyclo (Leu-Phe), Cyclo (Ser-Tyr), and Cyclo (Pro-Thr) at a high concentration. Specifically, Cyclo (Leu-Leu) is 8% or more (weight basis), Cyclo (Leu-Phe) is 8% or more, and Cyclo (Ser-) relative to the total amount of cyclic dipeptide in the heat treatment of soybean peptide. Tyr) is a heat treatment of 6% or more. In the heat treatment of the soybean peptide, the concentrations are 0.1 ppm/Bx (10 μg/100 g/Bx), preferably 5.0 ppm/Bx or more, more preferably 6.0 ppm/Bx or more, still more preferably 7.0 ppm/ Bx or more. Particularly preferably, the content of Cyclo (Leu-Leu) and Cyclo (Leu-Phe) is 10.0 ppm/Bx or more, preferably 12.0 ppm/Bx or more. The upper limit of these is not particularly limited, and is preferably It is 500 ppm/Bx or less, 400 ppm/Bx or less, more preferably 350 ppm/Bx or less, and still more preferably about 300 ppm/Bx or less.
乳清胜肽的原料不特別限定，可舉出例如屬乳清蛋白質的WPC(乳清蛋白濃縮物)、WPI(乳清蛋白分離物)等。乳清胜肽係指將此等乳清蛋白質以酵素等分解而得者。分解度係有高有低，分解度愈低，則乳臭味愈強而有溶解後的液性為不透明(白濁)之傾向。另一方面，分解度愈高則溶解時的液性愈呈透明，但有苦味、澀味增加的傾向。 The raw material of the whey peptide is not particularly limited, and examples thereof include WPC (whey protein concentrate) and WPI (whey protein isolate) which are whey proteins. The whey peptide means that the whey protein is decomposed by an enzyme or the like. The degree of decomposition is high or low, and the lower the degree of decomposition, the stronger the milky odor and the tendency for the liquid after dissolution to be opaque (white turbid). On the other hand, the higher the degree of decomposition, the more transparent the liquidity at the time of dissolution, but the bitterness and the astringency tend to increase.
乳清胜肽熱處理物係藉由將乳清胜肽進行高溫加熱處理或高溫高壓處理而得，透過該處理，大量的環狀二肽或其鹽即含於乳清胜肽熱處理物中。亦即，本發明中乳清胜肽熱處理物，其特徵之一為含有環狀二肽或其鹽。 The whey peptide heat treatment is obtained by subjecting the whey peptide to high temperature heat treatment or high temperature and high pressure treatment, and a large amount of the cyclic dipeptide or a salt thereof is contained in the whey peptide heat treatment by the treatment. That is, one of the characteristics of the whey peptide heat-treated product of the present invention is that it contains a cyclic dipeptide or a salt thereof.
又，本發明中的乳清胜肽熱處理物係分別以0.1ppm/Bx(10μg/100g/Bx)的濃度含有Cyclo(Arg-Leu)、Cyclo(Leu-Lys)、Cyclo(Ala-Leu)、Cyclo(Glu-Pro)、Cyclo(Ile-Pro)、Cyclo(Val-Phe)、Cyclo(Asp-Glu)、Cyclo(Thr-Lys)、Cyclo(Lys-Lys)、Cyclo(Lys-Phe)、及Cyclo(Thr-Tyr)。較佳為以0.5ppm/Bx以上，更佳為0.7ppm/Bx以上，再更佳為0.9ppm/Bx以上，特佳為1.0ppm/Bx以上，特佳為1.2ppm/Bx以上的濃度含有上述之環狀二肽或其鹽各者的 乳清胜肽熱處理物。 Further, the whey peptide heat-treated product of the present invention contains Cyclo (Arg-Leu), Cyclo (Leu-Lys), Cyclo (Ala-Leu), respectively, at a concentration of 0.1 ppm/Bx (10 μg/100 g/Bx). Cyclo (Glu-Pro), Cyclo (Ile-Pro), Cyclo (Val-Phe), Cyclo (Asp-Glu), Cyclo (Thr-Lys), Cyclo (Lys-Lys), Cyclo (Lys-Phe), and Cyclo (Thr-Tyr). It is preferably 0.5 ppm/Bx or more, more preferably 0.7 ppm/Bx or more, still more preferably 0.9 ppm/Bx or more, particularly preferably 1.0 ppm/Bx or more, and particularly preferably 1.2 ppm/Bx or more. Cyclic dipeptide or its salt Whey peptide heat treatment.
本發明之乳清胜肽熱處理物中每單位Bx之環狀二肽或其鹽的總量較佳為20000μg/100g/Bx以上、25000μg/100g/Bx以上、30000μg/100g/Bx以上，更佳為35000μg/100g/Bx以上。又，該總量較佳為10000mg/100g/Bx以下、5000mg/100g/Bx以下、2000mg/100g/Bx以下，更佳為1000mg/100g/Bx以下。典型上，本發明之乳清胜肽熱處理物中每單位Bx之環狀二肽或其鹽的總量較佳為20000μg/100g/Bx~10000mg/100g/Bx，更佳為30000μg/100g/Bx~5000mg/100g/Bx，再更佳為35000μg/100g/Bx~1000mg/100g/Bx。 The total amount of the cyclic dipeptide or a salt thereof per unit Bx in the whey peptide heat treatment of the present invention is preferably 20,000 μg/100 g/Bx or more, 25,000 μg/100 g/Bx or more, and 30,000 μg/100 g/Bx or more, more preferably It is 35000 μg / 100 g / Bx or more. Further, the total amount is preferably 10000 mg/100 g/Bx or less, 5000 mg/100 g/Bx or less, 2000 mg/100 g/Bx or less, more preferably 1000 mg/100 g/Bx or less. Typically, the total amount of the cyclic dipeptide per unit Bx or a salt thereof in the heat treatment of the whey peptide of the present invention is preferably from 20,000 μg / 100 g / Bx to 10000 mg / 100 g / Bx, more preferably 30,000 μg / 100 g / Bx. ~5000mg/100g/Bx, more preferably 35000μg/100g/Bx~1000mg/100g/Bx.
本發明中的乳清胜肽熱處理物較佳以高濃度含有Cyclo(Arg-Leu)、Cyclo(Leu-Lys)、Cyclo(Ala-Leu)、Cyclo(Glu-Pro)、Cyclo(Ile-Pro)、Cyclo(Val-Phe)、Cyclo(Asp-Glu)、Cyclo(Thr-Lys)。乳清胜肽熱處理物中，此等的濃度分別為0.1ppm/Bx(10μg/100g/Bx)以上，較佳為5.0ppm/Bx以上，更佳為6.0ppm/Bx以上，再更佳為7.0ppm/Bx以上。此等的上限不特別限定，較佳為500ppm/Bx以下、400ppm/Bx以下，更佳為350ppm/Bx以下，再更佳為300ppm/Bx以下左右。 The whey peptide heat treatment material of the present invention preferably contains Cyclo (Arg-Leu), Cyclo (Leu-Lys), Cyclo (Ala-Leu), Cyclo (Glu-Pro), Cyclo (Ile-Pro) at a high concentration. Cyclo (Val-Phe), Cyclo (Asp-Glu), Cyclo (Thr-Lys). In the whey peptide heat treatment, the concentrations are 0.1 ppm/Bx or more (10 μg/100 g/Bx) or more, preferably 5.0 ppm/Bx or more, more preferably 6.0 ppm/Bx or more, and still more preferably 7.0. Above ppm/Bx. The upper limit of these is not particularly limited, but is preferably 500 ppm/Bx or less, 400 ppm/Bx or less, more preferably 350 ppm/Bx or less, still more preferably about 300 ppm/Bx or less.
本發明一形態為一種含有動植物性胜肽熱處理物作為 有效成分的神經性疾病預防組成物。 One aspect of the present invention is a heat-treated product containing an animal or plant peptide A neurological disease prevention composition of an active ingredient.
本發明之組成物中的動植物性胜肽熱處理物的含量，只要是如考量其投予形態、投予方法等，而能夠獲得本發明所期望效果的量即可，不特別限定。例如，動植物性胜肽熱處理物的含量，相對於本發明之組成物的總重量為0.10重量%以上，較佳為0.20重量%以上，更佳為0.40重量%以上。又，動植物性胜肽熱處理物的含量，相對於本發明之組成物的總重量為50重量%以下，較佳為10重量%以下，更佳為5.0重量%以下。典型上，動植物性胜肽熱處理物的含量，相對於本發明之組成物的總重量為0.10重量%~50重量%，較佳為0.20重量%~10重量%，更佳為0.4重量%~5.0重量%。此外，若非特別合先敘明，則本說明書中所使用的「重量%」係指重量/重量(w/w)。 The content of the heat-treated product of the animal or plant peptide in the composition of the present invention is not particularly limited as long as it is a dosage form, a method of administration, or the like, and the desired effect of the present invention can be obtained. For example, the content of the heat-treated product of the animal or plant peptide is 0.10% by weight or more, preferably 0.20% by weight or more, and more preferably 0.40% by weight or more based on the total weight of the composition of the present invention. Further, the content of the heat-treated product of the animal or plant peptide is 50% by weight or less, preferably 10% by weight or less, and more preferably 5.0% by weight or less based on the total weight of the composition of the present invention. Typically, the content of the heat-treating substance of the animal or vegetable peptide is 0.10% by weight to 50% by weight, preferably 0.20% by weight to 10% by weight, more preferably 0.4% by weight to 5.0% by weight based on the total weight of the composition of the present invention. weight%. Further, "% by weight" as used in the specification means weight/weight (w/w) unless otherwise specified.
腦中存有屬中樞神經系統的構成細胞之一的小神經膠質細胞，其透過腦損傷部位的清掃機能或抗原呈現機能等，負責腦內的免疫防禦。此小神經膠質細胞一旦受到各種刺激而活化，便會釋放出發炎性細胞激素、一氧化氮、活性氧等液性因子，而引起存在於腦內之神經細胞的發炎。然後，因神經細胞的發炎，而促進失智症、精神分裂症、阿茲海默症、帕金森綜合症、肌肉萎縮性脊髓側索硬化症等神經性疾病的發病。從而，只要可抑制小神經膠質細胞之活化、發炎性細胞激素或一氧化氮、活性氧等液性 因子自小神經膠質細胞的釋放，便可抑制神經細胞的發炎，其結果，可發揮失智症、精神分裂症、阿茲海默症、帕金森綜合症、肌肉萎縮性脊髓側索硬化症等神經性疾病之預防效果。 In the brain, microglia, which is one of the constituent cells of the central nervous system, is responsible for the immune defense in the brain through the function of the brain damage or the function of antigen presentation. Once activated by various stimuli, the microglial cells release liquid factors such as inflammatory cytokines, nitric oxide, and active oxygen, which cause inflammation of nerve cells existing in the brain. Then, due to inflammation of nerve cells, the onset of neurological diseases such as dementia, schizophrenia, Alzheimer's disease, Parkinson's syndrome, and amyotrophic lateral sclerosis is promoted. Therefore, as long as it can inhibit the activation of microglia, inflammatory cytokines or liquid nitrogen such as nitric oxide and reactive oxygen species. The release of a factor from a small glial cell can inhibit the inflammation of nerve cells, and as a result, it can exert dementia, schizophrenia, Alzheimer's disease, Parkinson's syndrome, amyotrophic lateral sclerosis, and the like. The preventive effect of neurological diseases.
本發明之神經性疾病之預防用組成物，依據其形態，除動植物性胜肽熱處理物以外，亦可含有任意的添加劑、通常使用的任意成分。作為此等添加劑及/或成分的實例，除維生素E、維生素C等的維生素類、礦物質類、營養成分、香料等的生理活性成分外，尚可舉出在製劑化中摻混的賦形劑、黏合劑、乳化劑、張力劑(等滲壓劑)、緩衝劑、助溶劑、防腐劑、安定化劑、抗氧化劑、著色劑、凝固劑、或塗覆劑等，但不限定於此等。 The preventive composition for a neurological disease of the present invention may contain, in addition to the heat-treated product of the plant-derived peptide, an optional additive or an optional component which is usually used. As examples of such additives and/or components, in addition to vitamins, vitamins C, and the like, vitamins, minerals, nutrients, flavors, and the like, physiologically active ingredients such as vitamins, vitamins, and the like may be mentioned. , but not limited to, agents, binders, emulsifiers, tonicity agents (isotonic agents), buffers, solubilizers, preservatives, stabilizers, antioxidants, colorants, coagulants, or coating agents Wait.
本發明之神經性疾病之預防用組成物，透過使其含有前述之動植物性胜肽熱處理物作為有效成分，可抑制發炎性細胞激素、一氧化氮、活性氧等液性因子自小神經膠質細胞的釋放，尤為一氧化氮的釋放。藉此，可發揮抑制腦內神經細胞的發炎之效果。從而，透過攝取本發明之組成物，可獲得起因於神經細胞之發炎性異常的疾病，例如失智症、阿茲海默症、帕金森綜合症、精神分裂症、肌肉萎縮性脊髓側索硬化症等神經性疾病之預防效果。 The composition for preventing neurological diseases of the present invention can inhibit the inflammatory cytokines, nitric oxide, active oxygen and other liquid factors from microglia by using the above-mentioned heat-treated animal or plant peptide as an active ingredient. The release, especially the release of nitric oxide. Thereby, the effect of suppressing inflammation of nerve cells in the brain can be exerted. Therefore, by ingesting the composition of the present invention, diseases resulting from inflammatory abnormalities of nerve cells such as dementia, Alzheimer's disease, Parkinson's syndrome, schizophrenia, amyotrophic lateral sclerosis can be obtained. The preventive effect of neurological diseases such as symptoms.
本發明之神經性疾病之預防用組成物可例如對含有動植物性胜肽熱處理物的原料，視需求添加溶劑、分散劑、乳化劑、緩衝劑、安定劑、賦形劑、黏結劑、崩解劑、或潤滑劑等，依循周知之方法製劑化成錠劑、顆粒劑、散劑、粉末劑、或膠囊劑等的固形劑或一般的液劑、懸浮劑或乳劑等的液劑等。此等組成物可直接與水等共同服用。又，調製成可容易地摻混的形態(例如粉末形態或顆粒形態)後，例如，可作為醫藥品的原材料使用。 The preventive composition for a neurological disease of the present invention may, for example, be a raw material containing a heat-treated product of an animal or plant peptide, and a solvent, a dispersant, an emulsifier, a buffer, a stabilizer, an excipient, a binder, and a disintegration may be added as needed. The agent, the lubricant, and the like are formulated into a solid preparation such as a tablet, a granule, a powder, a powder, or a capsule according to a known method, or a liquid preparation such as a liquid preparation, a suspension, or an emulsion. These compositions can be taken directly with water or the like. Further, it can be used as a raw material of a pharmaceutical product after being prepared into a form that can be easily blended (for example, a powder form or a particle form).
就本發明而言，作為其一例，能以製劑之形態提供，但不限定於本形態。亦可將該製劑直接以組成物，或者以包含該製劑的組成物提供。作為其一例，能以醫藥等的形態提供，但不限定於本形態。作為本發明之組成物，可舉出醫藥組成物、飲食品組成物、食品組成物、飲料組成物、化妝用組成物等，但不限定於此等。作為食品組成物的非限定性實例，可舉出機能性食品、健康輔助食品、營養機能食品、特別用途食品、特定保健用食品、營養輔助食品、膳食療法用食品、健康食品、補充劑、食品添加物等。 The present invention can be provided in the form of a preparation as an example thereof, but is not limited to the present embodiment. The formulation may also be provided directly as a composition or as a composition comprising the formulation. As an example, it can be provided in the form of medicine, etc., but it is not limited to this form. Examples of the composition of the present invention include a pharmaceutical composition, a food and beverage composition, a food composition, a beverage composition, a cosmetic composition, and the like, but are not limited thereto. Non-limiting examples of the food composition include functional foods, health supplement foods, nutritional function foods, special purpose foods, specific health foods, nutritional supplement foods, dietetic foods, health foods, supplements, and foods. Additives, etc.
本發明之神經性疾病之預防用組成物對於治療用途(醫療用途)或非治療用途(非醫療用途)均可應用。具體而言，可舉出作為醫藥品、準醫藥品及化妝料的使用；又，可舉出作為藥事法上雖非屬於此等，但明示或暗示性地訴求神經性疾病預防效果、失智症預防效果、阿茲海默症預防效果、帕金森綜合症預防效果、精神分裂症預防效 果、肌肉萎縮性脊髓側索硬化症預防效果等之組成物的使用。 The composition for preventing neurological diseases of the present invention can be applied to therapeutic use (medical use) or non-therapeutic use (non-medical use). Specifically, it can be used as a pharmaceutical, a quasi-drug, and a cosmetic; and it is not mentioned as a pharmaceutical law, but it expressly or implicitly appeals to the prevention and loss of neurological diseases. Mental health prevention effect, Alzheimer's disease prevention effect, Parkinson's syndrome prevention effect, schizophrenia prevention effect The use of a composition such as a fruit, atrophic spinal side sclerosis prevention effect, and the like.
本發明，在另一方面，係有關於一種附有與神經性疾病之預防有關之機能之標示的前述神經性疾病之預防用組成物。此種標示或機能標示不特別限定，可舉出例如「預防神經性疾病」、「降低神經性疾病之發病風險」、「預防失智症」、「降低失智症之發病風險」、「預防阿茲海默症」、「降低阿茲海默症之發病風險」、「預防帕金森綜合症」、「降低帕金森綜合症之發病風險」、「預防精神分裂症」、「降低精神分裂症之發病風險」、「預防肌肉萎縮性脊髓側索硬化症」、或「降低肌肉萎縮性脊髓側索硬化症之發病風險」等。本說明書中，如該標示及機能標示之標示可附加於組成物本身，亦可附加於組成物的容器或包裝上。 In another aspect, the present invention relates to a preventive composition for the aforementioned neurological disease, which is accompanied by a function of a function related to prevention of a neurological disease. Such a label or a function label is not particularly limited, and examples thereof include "preventing a neurological disease", "reducing the risk of developing a neurological disease", "preventing dementia", "reducing the risk of dementia", and "prevention". Alzheimer's disease, "reducing the risk of developing Alzheimer's disease", "preventing Parkinson's disease", "reducing the risk of Parkinson's disease", "preventing schizophrenia", "lowering schizophrenia" Risk of onset, "prevention of amyotrophic lateral sclerosis", or "reducing the risk of developing amyotrophic lateral sclerosis". In this specification, the label of the label and the function label may be attached to the composition itself or may be attached to the container or package of the composition.
本發明之神經性疾病之預防用組成物能以因應其形態的適當方法來攝取。作為攝取方法，可舉出例如採內用(口服用)、外用、注射等的方法，但只要可發揮本發明所期望之效果，則其方法不特別限定。此外，本說明書中所稱「攝取」，係以包含攝取、服用或飲用等的全部形態使用。 The composition for preventing neurological diseases of the present invention can be ingested by an appropriate method in accordance with the form thereof. The method of ingestion is, for example, a method for internal use (for oral use), external use, injection, or the like. However, the method is not particularly limited as long as the desired effect of the present invention can be exerted. In addition, the term "ingestion" as used in the present specification is used in all forms including ingestion, administration, or drinking.
本發明之神經性疾病之預防用組成物的施用量係依據其形態、投予方法、使用目的及作為攝取對象之患者或患病動物的年齡、體重、症狀適時設定，非為一定。就本發明中之動植物性胜肽熱處理物的有效人類攝取量而言，雖 非為一定，例如，按體重50kg的人類每日較佳為500mg以上，更佳為1000mg以上。又，投予可在所期望的攝取量範圍內，於1日內分作單次或數次來進行。投予時間亦為任意者。此外，所稱動植物性胜肽熱處理物的有效人類攝取量，係指對人類顯示有效之效果的動植物性胜肽熱處理物的攝取量。 The application amount of the composition for preventing neurological diseases of the present invention is set according to the form, the administration method, the purpose of use, and the age, body weight, and symptoms of the patient or the diseased animal to be ingested, and are not constant. Regarding the effective human intake of the heat-treated animal of plant and animal peptides in the present invention, It is not necessary, for example, a human body having a body weight of 50 kg is preferably 500 mg or more per day, more preferably 1000 mg or more. Further, the administration can be carried out in a single or several times within one day within a desired intake amount range. The time of investment is also arbitrary. Further, the effective human intake amount of the heat-treated animal or plant peptide is an intake amount of an animal or vegetable peptide heat-treated product which exhibits an effective effect on humans.
本發明之神經性疾病之預防用組成物的施用對象較佳為人類，惟亦可為牛、馬、羊等的家畜動物、犬、貓、兔等的寵物動物或小鼠、大鼠、豚鼠、猴子等的實驗動物。以人類以外的動物為對象進行投予時，對小鼠每1個體約20g之每日的用量係因組成物中之有效成分的含量、施用對象的狀態、體重、性別及年齡等條件而異，通常，動植物性胜肽熱處理物的投予量較佳為100mg/kg以上，更佳為1000mg/kg以上。 The subject for the prophylactic use of the neurological disease of the present invention is preferably a human, but may be a livestock animal such as a cow, a horse, or a sheep, a pet animal such as a dog, a cat, or a rabbit, or a mouse, a rat, or a guinea pig. Experimental animals such as monkeys. When the animal is administered to an animal other than human, the daily dosage of about 20 g per mouse is different depending on the content of the active ingredient in the composition, the state of the object to be administered, the body weight, the sex, and the age. In general, the administration amount of the heat treatment product of the animal or plant peptide is preferably 100 mg/kg or more, more preferably 1000 mg/kg or more.
本發明一形態為一種動植物性胜肽熱處理物之用以預防神經性疾病的使用。 One aspect of the present invention is a use of a heat-treated animal or plant peptide for preventing the use of a neurological disease.
本發明之動植物性胜肽熱處理物的使用係包含用以預防例如失智症、阿茲海默症、帕金森綜合症、精神分裂症、肌肉萎縮性脊髓側索硬化症等的使用，但不限定於此等。又，該使用為針對人類或非人類動物的使用，可為治療性的使用或非治療性的使用。於此，所稱「非治療性」，係指不包含醫療行為，亦即藉由治療之對人體的處 理行為之概念。 The use of the heat-treated animal or plant peptide of the present invention includes use for preventing, for example, dementia, Alzheimer's disease, Parkinson's syndrome, schizophrenia, amyotrophic lateral sclerosis, etc., but not Limited to this. Again, the use is for the use of human or non-human animals and may be therapeutic or non-therapeutic. As used herein, the term "non-therapeutic" means not including medical treatment, that is, by treating the human body. The concept of rational behavior.
本發明一形態係提供一種包含對需要預防神經性疾病之對象，以動植物性胜肽熱處理物作為有效成分投予治療有效量的預防神經性疾病之方法。此外，所稱需要預防神經性疾病之對象，係與本發明之神經性疾病之預防用組成物的前述投予對象相同。 One aspect of the present invention provides a method for preventing a neurological disease by administering a heat-treated animal or plant peptide as an active ingredient to a subject in need of prevention of a neurological disease. Further, the subject to be treated for the prevention of a neurological disease is the same as the above-mentioned administration target of the preventive composition for a neurological disease of the present invention.
此外，本說明書中所稱治療有效量，係指使上述對象攝取本發明之動植物性胜肽熱處理物時，與未予攝取的對象相比，更可預防神經性疾病的量。就具體的有效量而言，係隨投予形態、投予方法、使用目的及對象的年齡、體重、症狀等適時設定，非為一定。 In addition, the therapeutically effective amount referred to in the present specification refers to an amount which can prevent a neurological disease as compared with a subject which is not ingested when the subject is ingested with the heat-treated animal of the animal or plant peptide of the present invention. The specific effective amount is set according to the administration form, the administration method, the purpose of use, and the age, weight, and symptoms of the subject, and is not constant.
於本發明之方法中，可直接投予動植物性胜肽熱處理物，或者將其調成含有動植物性胜肽熱處理物的組成物來投予，以達到前述治療有效量。 In the method of the present invention, the heat treatment of the animal or vegetable peptide can be directly administered, or it can be administered into a composition containing the heat-treated product of the animal or plant peptide to achieve the aforementioned therapeutically effective amount.
根據本發明之方法，可預防神經性疾病而不會產生副作用。 According to the method of the present invention, a neurological disease can be prevented without causing side effects.
以下，根據實施例對本發明更詳細地加以說明，惟本發明之範圍不受此限定。本領域具有通常知識者可對本發明之方法施以種種變更、修飾而使用，且此等亦包含於本發明之範圍。 Hereinafter, the present invention will be described in more detail based on the examples, but the scope of the invention is not limited thereto. Those skilled in the art can use various modifications and changes to the methods of the present invention, and these are also included in the scope of the present invention.
作為植物性胜肽係使用大豆胜肽，在液體中進行高溫高壓處理而製成大豆胜肽熱處理物。具體而言，係對3g的大豆胜肽(HINUTE AM，不二製油公司製)添加15ml的蒸餾水，予以置入高壓釜(TOMY SEIKO公司製)，施加135℃、0.31MPa、3小時高溫高壓處理。又，作為比較例，係調製使用相同胜肽而未進行高溫高壓處理的大豆胜肽未加熱物。 The soybean peptide is used as a plant peptide, and is subjected to high temperature and high pressure treatment in a liquid to prepare a heat treatment product of soybean peptide. Specifically, 15 g of distilled water was added to 3 g of soybean peptide (HINUTE AM, manufactured by Fuji Oil Co., Ltd.), placed in an autoclave (manufactured by TOMY SEIKO Co., Ltd.), and subjected to high temperature and high pressure treatment at 135 ° C, 0.31 MPa, and 3 hours. . Further, as a comparative example, a soybean peptide unheated product which was subjected to high temperature and high pressure treatment using the same peptide was prepared.
作為動物性胜肽係使用乳清胜肽，在液體中進行高溫高壓處理而製成乳清胜肽熱處理物。具體而言，係對3g的Whey Peptide Peptigen IF-3090(Arla Foods公司製，平均分子量300~400)、平均分子量440的乳清胜肽、或Casein Peptide CU2500A(森永乳業公司製，平均分子量375)添加30ml的蒸餾水，予以置入高壓釜(TOMY SEIKO公司製)，施加135℃、0.31MPa、3小時高溫高壓處理。又，作為比較例，係調製使用相同胜肽而未進行高溫高壓處理的乳清胜肽未加熱物。此外，第3圖及第4圖所記載之乳清胜肽未加熱物3及熱處理物3係來自Whey Peptide Peptigen IF-3090；乳清胜肽未加熱物5及熱處理物5係來自平均分子量440的乳清胜肽；乳清胜肽未加熱物7及熱處理物7則來自Casein Peptide CU2500A。 The whey peptide is used as an animal peptide, and is subjected to high temperature and high pressure treatment in a liquid to prepare a whey peptide heat-treated product. Specifically, 3 g of Whey Peptide Peptigen IF-3090 (manufactured by Arla Foods, average molecular weight 300 to 400), whey peptide having an average molecular weight of 440, or Casein Peptide CU2500A (manufactured by Morinaga Dairy Co., Ltd., average molecular weight 375) 30 ml of distilled water was added and placed in an autoclave (manufactured by TOMY SEIKO Co., Ltd.), and 135 ° C, 0.31 MPa, and high temperature and high pressure treatment were applied for 3 hours. Further, as a comparative example, a whey peptide unheated product which was not subjected to high temperature and high pressure treatment using the same peptide was prepared. Further, the whey peptide unheated material 3 and the heat-treated product 3 described in Figs. 3 and 4 are derived from Whey Peptide Peptigen IF-3090; the whey peptide unheated material 5 and the heat-treated product 5 are derived from an average molecular weight of 440. Whey peptide; whey peptide unheated 7 and heat treated 7 from Casein Peptide CU2500A.
在添加大豆或乳清胜肽熱處理物的條件下，評定由LPS刺激BV2小神經膠質細胞產生之一氧化氮的抑制效果。在96井盤中，對各井播種各100μL的以添加有10%FBS之DMEM培養基調整成2.0×105細胞/mL之濃度的BV2小神經膠質細胞。在播種24小時後以LPS(最終濃度100ng/mL)與環狀二肽(最終濃度5mg/mL)同時添加。進一步於24小時後回收培養上清液，藉由Griess分析法測定一氧化氮的代謝物量(NO2 -)(n=2)。Griess分析法係使用Griess Reagent System(與Promega cat.#G2930相同之組成品)來進行。 The inhibitory effect of one of the nitric oxides produced by the LPS-stimulated BV2 microglial cells was evaluated under the condition that the heat treatment of soybean or whey peptide was added. In a 96 well plate, 100 μL of DV medium supplemented with 10% FBS was added to each well to adjust BV2 microglia at a concentration of 2.0 × 10 5 cells/mL. After 24 hours of sowing, LPS (final concentration 100 ng/mL) was added simultaneously with the cyclic dipeptide (final concentration 5 mg/mL). Further, the culture supernatant was recovered after 24 hours, and the amount of metabolite of nitric oxide (NO 2 - ) (n = 2) was determined by Griess analysis. The Griess analysis method was carried out using the Griess Reagent System (the same composition as Promega cat. #G2930).
將結果示於第1圖~第4圖。實驗的結果，如第1圖及第2圖所示，藉由同時添加大豆胜肽熱處理物與LPS，起因於LPS刺激之一氧化氮的代謝物(NO2 -)自BV2小神經膠質細胞的產生，顯然隨大豆胜肽熱處理物的濃度增加而獲抑制。再者，由添加大豆胜肽熱處理物而抑制起因於LPS刺激之一氧化氮的代謝物(NO2 -)自BV2小神經膠質細胞的產生之程度，與大豆胜肽未加熱物相比亦顯然較高。 The results are shown in Figures 1 to 4. As a result of the experiment, as shown in Fig. 1 and Fig. 2, by adding a heat treatment of soybean peptide and LPS simultaneously, LPS stimulates one of the metabolites of nitric oxide (NO 2 - ) from BV2 microglia. The production, apparently, is inhibited as the concentration of the heat treatment of the soybean peptide is increased. Furthermore, the degree of inhibition of the production of nitric oxide metabolite (NO 2 - ) derived from LPS stimulation from BV2 microglial cells by the addition of the heat treatment substance of the soybean peptide is also apparent compared with the unheated substance of the soybean peptide. Higher.
又，如第3圖及第4圖所示，藉由同時添加乳清胜肽 熱處理物與LPS，起因於LPS刺激之一氧化氮的代謝物(NO2 -)自BV2小神經膠質細胞的產生，顯然隨乳清胜肽熱處理物的濃度增加而獲抑制。另一方面，同時添加乳清胜肽未加熱物與LPS時，則未看出抑制起因於LPS刺激之一氧化氮的代謝物(NO2 -)自BV2小神經膠質細胞的產生之效果。 Further, as shown in Fig. 3 and Fig. 4, by adding whey peptide heat treatment and LPS simultaneously, LPS stimulates the production of a nitric oxide metabolite (NO 2 - ) from BV2 microglia. It is apparent that it is suppressed as the concentration of the whey peptide heat treatment increases. On the other hand, when whey peptide unheated material and LPS were simultaneously added, the effect of suppressing the production of a nitric oxide metabolite (NO 2 - ) derived from BPS2 microglial cells by LPS stimulation was not observed.
從而，顯然大豆或乳清胜肽熱處理物可顯著抑制起因於LPS刺激之一氧化氮自BV2小神經膠質細胞的產生。 Thus, it is apparent that the heat treatment of soybean or whey peptide can significantly inhibit the production of nitric oxide from BV2 microglia, which is caused by LPS stimulation.
本發明係提供一種含有動植物性胜肽熱處理物作為有效成分的神經性疾病之預防用組成物。從而，本發明由於可提供一種用以預防失智症、精神分裂症、阿茲海默症、帕金森綜合症、肌肉萎縮性脊髓側索硬化症等神經性疾病的新穎手段，產業上的利用性極高。 The present invention provides a composition for preventing neurological diseases containing a heat-treated animal of plant and animal peptide as an active ingredient. Therefore, the present invention provides a novel means for preventing neurological diseases such as dementia, schizophrenia, Alzheimer's disease, Parkinson's syndrome, and muscle atrophic lateral sclerosis, and industrial use. Extremely high.
Claims (15)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016002493 | 2016-01-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW201733607A true TW201733607A (en) | 2017-10-01 |
Family
ID=59273726
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW106100494A TW201733607A (en) | 2016-01-08 | 2017-01-06 | Composition for preventing neurological diseases |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPWO2017119476A1 (en) |
| TW (1) | TW201733607A (en) |
| WO (1) | WO2017119476A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7011984B2 (en) * | 2018-07-13 | 2022-01-27 | キリンホールディングス株式会社 | Composition for improving attention function and judgment function |
| WO2022131026A1 (en) * | 2020-12-18 | 2022-06-23 | Suntory Holdings Limited | Use of cyclic dipeptides in production of agent for inhibiting decline in cognitive function or ameliorating cognitive dysfunction |
| WO2024095906A1 (en) * | 2022-11-01 | 2024-05-10 | サントリーホールディングス株式会社 | Composition for preventing or inhibiting inflammation of neural cells |
| WO2024262349A1 (en) * | 2023-06-19 | 2024-12-26 | サントリーホールディングス株式会社 | COMPOSITION FOR SUPPRESSING OR AMELIORATING DETERIORATION OF COGNITIVE FUNCTION, AND COMPOSITION FOR INHIBITING β-SECRETASE |
| KR102835798B1 (en) * | 2024-07-05 | 2025-07-21 | 주식회사 비플럭스파머 | Composition for muscle growth and improvement, and treatment and prevention of muscle wasting diseases, comprising Bombycis batryticatus or a cyclic peptide derived therefrom as an active ingredient |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG178213A1 (en) * | 2009-12-25 | 2012-03-29 | Suntory Holdings Ltd | Learning motivation improvers |
| SG11201510062VA (en) * | 2013-06-10 | 2016-01-28 | Suntory Holdings Ltd | Plant extract containing diketopiperazine and method for producing same |
-
2017
- 2017-01-06 WO PCT/JP2017/000244 patent/WO2017119476A1/en not_active Ceased
- 2017-01-06 JP JP2017560427A patent/JPWO2017119476A1/en active Pending
- 2017-01-06 TW TW106100494A patent/TW201733607A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPWO2017119476A1 (en) | 2018-11-01 |
| WO2017119476A1 (en) | 2017-07-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6669750B2 (en) | Composition for inhibiting serum carnosine degrading enzyme containing cyclic dipeptide | |
| TW201733607A (en) | Composition for preventing neurological diseases | |
| JP6839080B2 (en) | Composition for inhibiting serum carnosine degrading enzyme containing animal and plant-derived peptides | |
| JP6713981B2 (en) | Lipase inhibitor | |
| TW201716079A (en) | Composition for promoting glp-2 secretion | |
| TW201716080A (en) | Composition for stimulating trpv1 | |
| KR102178926B1 (en) | A composition for reinforcing immune function and anti-fatigue comprising fermented placenta and its use | |
| WO2017119481A1 (en) | Cyclic dipeptide-containing composition for preventing neurological diseases | |
| CN107922458B (en) | Composition containing amino acid and cyclic dipeptide | |
| JP6671367B2 (en) | Anti-obesity composition containing cyclic dipeptide | |
| KR20140106058A (en) | Composition for enhancing immunological activity comprising soluble salmon milt extract and vegetable lactic acid bacteria | |
| JP6661597B2 (en) | α-glucosidase inhibitor | |
| JP6770515B2 (en) | Composition for lowering blood pressure | |
| TW201716066A (en) | Composition for inhibiting alcohol absorption | |
| JP6786490B2 (en) | Anti-obesity composition | |
| JP6687619B2 (en) | Composition for antagonisting melanin-concentrating hormone receptor | |
| KR20210076222A (en) | Calcium absorption promoting composition comprising cocoon hydrolysate |