CN113402587A - 一种八肽及其在制备改善记忆的药品和保健品中的应用 - Google Patents
一种八肽及其在制备改善记忆的药品和保健品中的应用 Download PDFInfo
- Publication number
- CN113402587A CN113402587A CN202110773378.5A CN202110773378A CN113402587A CN 113402587 A CN113402587 A CN 113402587A CN 202110773378 A CN202110773378 A CN 202110773378A CN 113402587 A CN113402587 A CN 113402587A
- Authority
- CN
- China
- Prior art keywords
- octapeptide
- use according
- memory
- polypeptide
- health
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 20
- 230000015654 memory Effects 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims description 8
- 229940079593 drug Drugs 0.000 title description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 28
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 19
- 230000036542 oxidative stress Effects 0.000 claims abstract description 17
- 229920001184 polypeptide Polymers 0.000 claims abstract description 17
- 210000002569 neuron Anatomy 0.000 claims abstract description 12
- 230000036541 health Effects 0.000 claims abstract description 10
- 239000003094 microcapsule Substances 0.000 claims abstract description 10
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 2
- 239000000463 material Substances 0.000 claims description 12
- 239000005913 Maltodextrin Substances 0.000 claims description 6
- 229920002774 Maltodextrin Polymers 0.000 claims description 6
- 239000011162 core material Substances 0.000 claims description 6
- 229940035034 maltodextrin Drugs 0.000 claims description 6
- 239000003826 tablet Substances 0.000 claims description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 5
- 108010010803 Gelatin Proteins 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 229920000159 gelatin Polymers 0.000 claims description 5
- 239000008273 gelatin Substances 0.000 claims description 5
- 235000019322 gelatine Nutrition 0.000 claims description 5
- 235000011852 gelatine desserts Nutrition 0.000 claims description 5
- 150000003904 phospholipids Chemical class 0.000 claims description 4
- 229920001661 Chitosan Polymers 0.000 claims description 3
- 239000001110 calcium chloride Substances 0.000 claims description 3
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 235000021323 fish oil Nutrition 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 229920000858 Cyclodextrin Polymers 0.000 claims description 2
- 239000001116 FEMA 4028 Substances 0.000 claims description 2
- 229920002907 Guar gum Polymers 0.000 claims description 2
- 102000004407 Lactalbumin Human genes 0.000 claims description 2
- 108090000942 Lactalbumin Proteins 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
- 229940072056 alginate Drugs 0.000 claims description 2
- 235000010443 alginic acid Nutrition 0.000 claims description 2
- 229920000615 alginic acid Polymers 0.000 claims description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 2
- 229960004853 betadex Drugs 0.000 claims description 2
- 235000013361 beverage Nutrition 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229940045110 chitosan Drugs 0.000 claims description 2
- 235000013365 dairy product Nutrition 0.000 claims description 2
- 229940014259 gelatin Drugs 0.000 claims description 2
- 239000000665 guar gum Substances 0.000 claims description 2
- 235000010417 guar gum Nutrition 0.000 claims description 2
- 229960002154 guar gum Drugs 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 230000006993 memory improvement Effects 0.000 claims description 2
- 239000001814 pectin Substances 0.000 claims description 2
- 229920001277 pectin Polymers 0.000 claims description 2
- 235000010987 pectin Nutrition 0.000 claims description 2
- 229960000292 pectin Drugs 0.000 claims description 2
- 239000000419 plant extract Substances 0.000 claims description 2
- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 2
- 235000013824 polyphenols Nutrition 0.000 claims description 2
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims description 2
- 239000011573 trace mineral Substances 0.000 claims description 2
- 235000013619 trace mineral Nutrition 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 abstract description 26
- 208000010340 Sleep Deprivation Diseases 0.000 abstract description 11
- 208000026139 Memory disease Diseases 0.000 abstract description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 6
- 230000003492 excitotoxic effect Effects 0.000 abstract description 4
- 231100000063 excitotoxicity Toxicity 0.000 abstract description 4
- 235000013305 food Nutrition 0.000 abstract description 4
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 230000001079 digestive effect Effects 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 42
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 33
- 230000000694 effects Effects 0.000 description 28
- 239000002609 medium Substances 0.000 description 18
- 229930195712 glutamate Natural products 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 16
- 230000029087 digestion Effects 0.000 description 16
- 239000004220 glutamic acid Substances 0.000 description 16
- 235000013922 glutamic acid Nutrition 0.000 description 16
- 239000000047 product Substances 0.000 description 14
- 230000002496 gastric effect Effects 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 description 11
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000011259 mixed solution Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 108010087230 Sincalide Proteins 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 238000010609 cell counting kit-8 assay Methods 0.000 description 5
- 230000003833 cell viability Effects 0.000 description 5
- 206010027175 memory impairment Diseases 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 230000000975 bioactive effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000012737 fresh medium Substances 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 230000000324 neuroprotective effect Effects 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 230000006886 spatial memory Effects 0.000 description 4
- 230000009182 swimming Effects 0.000 description 4
- 108010018924 Heme Oxygenase-1 Proteins 0.000 description 3
- 102100028006 Heme oxygenase 1 Human genes 0.000 description 3
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 3
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 3
- 102000057297 Pepsin A Human genes 0.000 description 3
- 108090000284 Pepsin A Proteins 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229940111202 pepsin Drugs 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 238000004088 simulation Methods 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 2
- 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 2
- 101000973778 Homo sapiens NAD(P)H dehydrogenase [quinone] 1 Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 238000012347 Morris Water Maze Methods 0.000 description 2
- 102100022365 NAD(P)H dehydrogenase [quinone] 1 Human genes 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 238000010811 Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 208000037887 cell injury Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000003061 neural cell Anatomy 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010013647 Drowning Diseases 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229920000294 Resistant starch Polymers 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 235000021120 animal protein Nutrition 0.000 description 1
- 230000006851 antioxidant defense Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000001964 calcium overload Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000008809 cell oxidative stress Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940118019 malondialdehyde Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000007180 physiological regulation Effects 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000004461 rapid eye movement Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 235000021254 resistant starch Nutrition 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
- A23P10/00—Shaping or working of foodstuffs characterised by the products
- A23P10/30—Encapsulation of particles, e.g. foodstuff additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- 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)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Neurosurgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurology (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Psychiatry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Hospice & Palliative Care (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明公开了一种八肽及其在制备改善记忆的药品和保健品中的应用。该多肽的氨基酸序列为:Trp‑Cys‑Pro‑Phe‑Ser‑Arg‑Ser‑Phe(WCPFSRSF)。本发明的八肽能改善睡眠剥夺诱导的小鼠记忆障碍,并且能显著地抑制神经细胞的兴奋性毒性和氧化应激。本发明的多肽既可以单独应用于改善记忆的保健品,也可以与其他具有改善记忆的活性成分进行复配使用,还可以制备成微胶囊,以改善多肽的胃肠道消化稳定性、生物利用度和保质期,从而更好地应用于食品工业和保健品领域。
Description
技术领域
本发明涉及一种八肽及其在制备改善记忆的药品和保健品中的应用。
背景技术
谷氨酸是大脑中主要的氨基酸类兴奋性神经递质。当谷氨酸在突触间隙中积累过多时,细胞外高浓度的谷氨酸会导致谷氨酸受体的过度刺激,进而导致钙超载,并导致氧化应激和凋亡,最终导致细胞损伤和神经元丢失,甚至引发神经退行性疾病。反之,钙离子流的升高进一步加剧了氧化应激并加速了神经元死亡,这种现象称为兴奋性毒性。谷氨酸的兴奋性毒性是导致神经元死亡的主要原因,其与多种神经系统疾病如阿尔茨海默病,缺血性脑中风等密切相关。因此,谷氨酸损伤的神经细胞模型常用于记忆障碍的研究。
大脑中的神经元大多不可再生,且神经退行性疾病具有较长的潜伏期,因此,选择适当的时机进行药物干预和早期预防神经元死亡是改善记忆障碍和预防神经相关疾病的重要因素。其中,氧化应激与记忆障碍和神经退行性疾病的早期发生密切相关。因此,抑制氧化应激来保护神经元进而改善记忆障碍成为一种重要的治疗策略。近年来,Nrf2这一与氧化还原密切相关的核转录因子,成为治疗和改善记忆障碍的重要靶点。直接激活Nrf2相关通路或采用具有激活Nrf2作用的安全有效的成分进行治疗,进而调控抗氧化防御系统,是治疗和改善记忆障碍的有效策略。
生物活性肽是由2-20个氨基酸以肽键连接成的具有多种人体代谢和生理调节功能的一类化合物,其对保健食品及药物的开发具有极其重要的作用,近些年受到研究者们的广泛关注。生物活性肽具有来源广泛、制备简单、无毒性作用、具有多种生理活性等优点。不同食源性的动植物蛋白的酶解产物对认知功能障碍类动物模型具有改善学习和记忆作用。有研究表明,生物活性肽可通过促进Nrf2的激活和核转录来促进其靶基因的转录和翻译来抑制氧化应激。
生物活性肽经口服后,需要经过胃肠道消化屏障,极易被胃蛋白酶和胰蛋白酶降解成更小的片段,使其活性受到影响。此外,多肽类药物还存在稳定性差、半衰期短,生物利用度低、易被体内蛋白酶或多肽酶降解等缺点,极大地限制了其应用。因此,保护多肽的结构稳定性和功能稳定性、提高其生物利用度已成为多肽领域的重要研究方向。
发明内容
本发明的目的在于提供一种具有改善记忆功效的八肽,及其在制备相关药品和保健品中的应用。
本发明的目的通过下述技术方案实现:
一种八肽,其氨基酸序列为Trp-Cys-Pro-Phe-Ser-Arg-Ser-Phe(WCPFSRSF)。
所述的八肽可通过现有化学合成方法获得,如固相化学合成法。
本发明的八肽可以用于制备改善记忆的药品和保健品,尤其是缓解神经细胞氧化应激相关症状,比如降低神经细胞的氧化应激水平,减少神经元损伤。
本发明采用细胞和动物实验证明了所述八肽可以缓解神经细胞的兴奋性毒性和氧化应激,并且所述八肽可以抑制谷氨酸诱导的神经细胞的损伤,从而发挥神经保护作用,可以用于制备治疗细胞氧化应激相关疾病的药物和保健品。
所述缓解神经细胞的氧化应激是指降低谷氨酸诱导的细胞活性氧的含量,提高细胞内抗氧化酶的活性如SOD和GSH-px,降低细胞内丙二醛的含量,调控氧化防御相关的Nrf2/HO-1通路等。
所述的神经细胞是人神经母细胞瘤细胞(SH-SY5Y细胞)。
所述改善记忆的药物和保健品还含有其他活性组分和辅料;
所述的其他活性组分包括植物提取物、维生素类、多酚类、鱼油、多不饱和脂肪酸类、乳制品及提取物、微量元素、磷脂类。
所述的药物和保健品可以是现有技术的各种类型,如饮料、口服液、胶囊、微胶囊、片剂、粉剂、颗粒剂、悬混剂;
所述的微胶囊包括芯材和壁材,芯材与壁材的质量比为1:(4-10);
所述壁材的材料包括壳聚糖、瓜儿多胶、麦芽糊精、明胶、阿拉伯胶、果胶、β-环糊精、海藻酸盐、乳清蛋白、磷脂、羧甲基纤维素、氯化钙的一种或多种。
本发明相对于现有技术具有如下的优点及效果:
1、本发明的八肽可以抑制神经元受损或死亡、又可以抑制细胞的氧化应激,改善记忆障碍。同时,该八肽可以由化学方法合成,无毒副作用,具有很好的安全性和实用性。
2、本发明的八肽既可作为功效成分单独应用于制备改善神经细胞氧化应激相关疾病的药品和保健品,也可与其他活性成分一起复配制备组合物。
3、本发明提供的微胶囊改善了八肽和/或其他活性成分的结构稳定性和功能稳定性、延长了保质期、并且提高了活性成分的生物利用度,具有更好的应用前景。
附图说明
图1是八肽对谷氨酸诱导的SH-SY5Y细胞的细胞存活率的影响。
图2是八肽对谷氨酸诱导的SH-SY5Y细胞的乳酸脱氢酶的影响。
图3是八肽对谷氨酸诱导的SH-SY5Y细胞的氧化应激的影响。
图4是八肽对谷氨酸诱导的SH-SY5Y细胞的Nrf2通路的影响。
图5是八肽经体外模拟胃肠道消化后的提取离子流图(EIC,m/z 515.2310);
图6是八肽经体外模拟胃肠道消化后的总离子流图;
其中,WCPFSRSF-G是八肽经胃消化后的产物,WCPFSRSF-GI是八肽经胃肠消化后的产物。
图7是体外模拟胃肠道消化对多肽神经保护作用的影响;
其中,WCPFSRSF-G是八肽经胃消化后的产物,WCPFSRSF-GI是八肽经胃肠消化后的产物。
具体实施方式
下面结合实施例及附图对本发明作进一步详细的描述,但本发明的实施方式不限于此。
本发明中,细胞培养方法和细胞存活率的测定如下:
SH-SY5Y细胞在MEM:F12完全培养基中培养,该培养基中添加了10%(v/v)的胎牛血清,1%非必需氨基酸,1%丙酮酸钠和1%谷氨酰胺,将细胞置于37℃且含有5%的CO2的恒温培养箱中培养。每隔6-8天细胞长满至百分之八九十后传代。取处于对数生长期的细胞用于实验。
将SH-SY5Y细胞以2×105个/mL的密度接种在透明96孔板中。每个组设置6个孔,实验组分为模型组和样品组,同时设置空白孔和对照孔。24小时后,弃掉培养基,模型组更换含有37.5mM谷氨酸的培养基处理24小时,样品组更换含有样品和谷氨酸的培养基处理24小时,空白孔更换新鲜的培养基。检测前每孔加入10μL CCK-8试剂,继续放入培养箱中孵育2-3h,采用酶标仪在450nm波长处检测吸光值OD值。
细胞存活率(%)=(A实验组-A空白组)/(A对照组-A空白组)×100%
A实验组:接种细胞,模型组为加入含有谷氨酸的培养基,加入CCK-8后各孔的吸光度;接种细胞,样品组为加入含有谷氨酸和八肽的培养基,加入CCK-8后各孔的吸光度。
A对照组:接种细胞,并加入培养基,加入CCK-8后各孔的吸光度。
A空白组:不接种细胞,加入培养基和CCK-8试剂后各孔的吸光度。
上述所选择的谷氨酸浓度为SH-SY5Y细胞达到半数致死量时的药物浓度,作为后续试验的药物浓度。
实施例1
固相合成法合成多肽WCPFSRSF,包括以下步骤:将二氯树脂溶胀、洗涤,脱除Fmoc保护基,加入多肽的组成氨基酸进行缩合反应,重复脱除-保护-缩合的过程,直至所有氨基酸连接完毕。用反相高效液相色谱法纯化,得到多肽纯品(>95%)。
实施例2
八肽对谷氨酸诱导的神经细胞细胞存活率的影响。如图1所示,50μM和100μM的WCPFSRSF处理的细胞存活率分别为69.03±1.21%和87.00±3.21%。而阳性对照的药物:脑活素(0.5mg/mL)处理的细胞存活率为67.58±1.79%。
检测结果表明,该八肽WCPFSRSF具有较好的神经保护作用。
实施例3
乳酸脱氢酶(lactate dehydrogenase,LDH)的测定
将SH-SY5Y细胞以2×105个/mL的密度接种在透明96孔板中,加入培养基。每个实验组设置6个孔,同时设置空白孔和对照孔。24小时后,弃掉培养基,模型组更换含有37.5mM谷氨酸的培养基,样品组更换同时含有谷氨酸和样品的培养基,同时以脑活素(0.5mg/mL)作为阳性对照,空白组和对照组更换新鲜的培养基,培养24小时。检测前结束培养,取上清液,按照说明书采用乳酸脱氢酶试剂盒进行测定。
如图2所示,经检测结果表明,谷氨酸处理组的LDH释放率为136.61±5.86%,而100μM的WCPFSRSF处理的LDH释放率显示降低,为108.82±7.32%,且低于阳性药物脑活素处理组119.23±3.90%。
实施例4八肽对谷氨酸诱导的氧化应激的影响
将SH-SY5Y细胞以2×105个/mL的密度接种在培养皿中,加入培养基。24小时后弃掉培养基,模型组更换含有37.5mM谷氨酸的培养基,样品组更换同时含有谷氨酸和八肽的培养基,对照组和空白组更换新鲜的培养基。24小时后结束培养,弃掉培养基,用PBS清洗3次,收集细胞,在离心后的细胞中加入200μL RIPA裂解液(含有1%PMSF),冰上裂解30min,裂解结束后将细胞置于4℃12000g离心10min,收集上清用于BCA蛋白定量,并将其余上清置于-80℃备用。
采用试剂盒测定SOD和GSH-PX的活力,MDA的含量以及GSH/GSSH。根据试剂盒说明书进行测定。
图3显示了八肽对谷氨酸诱导的SH-SY5Y细胞氧化应激指标的测定情况。如图所示,谷氨酸处理的细胞抗氧化酶如SOD和GSH-px的活力均显著下降(p<0.05),而八肽处理则显著逆转了谷氨酸诱导的抗氧化酶活力的下降(p<0.05)。
同样,细胞内的GSH/GSSH也被谷氨酸处理显著降低(p<0.05),而八肽的处理显著地改善了这一趋势。MDA是脂质过氧化的产物,可用于评判细胞的氧化水平。如图所示,谷氨酸处理组的细胞中MDA的水平显著升高(p<0.05),而八肽处理显著地降低了细胞中的MDA水平(p<0.05)。
实施例5八肽对谷氨酸诱导的Nrf2通路的影响
将SH-SY5Y细胞以2×105个/mL的密度接种在培养皿中,加入培养基。24小时后弃掉培养基,模型组更换含有37.5mM谷氨酸的培养基,样品组更换同时含有谷氨酸和八肽的培养基,空白组和对照组更换新鲜的培养基。24小时后结束培养,弃掉培养基,用PBS清洗3次,收集细胞,在离心后的细胞中加入200μL RIPA裂解液(含有1%PMSF),冰上裂解20-30min,裂解结束后置于4℃12000g离心10min,收集上清用于BCA蛋白定量,将上清与buffer混合,随后置于沸水浴中煮沸10min,在4℃,12000g的条件下离心10min,随后采用Westernblot技术测定Nrf2相关的抗氧化基因的蛋白表达水平。
上述Nrf2相关的蛋白是指Nrf2,HO-1,NQO1等。
检测结果表明,如图4所示,该八肽可以提高Nrf2,HO-1,NQO1的蛋白表达水平。
实施例6八肽对睡眠剥夺诱导记忆障碍小鼠的影响
选取SPF级雄鼠(C57BL/6(J)小鼠,)3~4周龄,18-22g。小鼠于实验前7d置于实验室适应环境。饲养环境:室温(25±2)℃,相对湿度50%-60%,12/12h明暗交替,小鼠可以自由饮食、摄水。适应1周后,将小鼠随机分组(每组12只):分别为正常组,睡眠剥夺组,WCPFSRSF组(30mg/kg/d)。正常组及模型组灌服等体积的生理盐水,每天灌胃1次,连续灌胃18天。
睡眠剥夺是采用改良的多平台方法进行的。第16天上午8点开始连续2天对小鼠进行睡眠剥夺。在水箱中放置了18个平台(直径3厘米,高度5厘米),水箱中水的高度为4厘米,小鼠可以自由移动,从一个平台跳到另一个平台。将足够的食物和水放在盒子的顶部,小鼠可以随意进食。当小鼠达到当小鼠达到睡眠的快速眼动阶段时,小鼠可能会肌肉无力而掉入水中。小鼠随后醒来,将尝试爬上平台以避免淹死。整个实验过程中保持水箱的水洁净。
通过Morris水迷宫测试评估小鼠的学习和记忆,包括定位航行试验(placenavigation)和空间探索试验(probe test)两个部分。
Morris水迷宫用于评估小鼠的长期空间记忆。该设备由一个充满水(24–26℃)的圆形水池组成,并分成四个象限。将平台设置高于水面1-2厘米,并放置在第三象限中。在灌胃的第14天开始进行定位航行试验训练,将小鼠面向池壁依次放入4个象限中,记录小鼠找到潜伏平台的时间为逃避潜伏期。若小鼠在120s内未找到安全平台,则将其轻轻地引导至平台,让小鼠在平台上停留10s,并记录逃逸潜伏期120s。采用摄像机监控小鼠的行为,并通过计算机化进行图像数据分析。
为了评估空间记忆,在上述最后一次训练后的24小时后进行了空间探索测试。在测试中,将平台从水箱中取出,将小鼠面对池壁置于迷宫的一个新的起始位置,测试其120s内在平台象限区域的游泳时间(目标象限游泳时间)和游泳距离(目的象限游泳距离),和穿越平台次数。在最后一次空间探索实验之后,将所有小鼠处死以收集组织。测试结果如表1和表2所示。
表1八肽对睡眠剥夺诱导记忆障碍小鼠定位航行能力的影响
#代表与对照组比较,p<0.05。*表示与模型组比较,p<0.05。
由表1可知,模型组的小鼠逃避潜伏期和总路程显著低于对照组(p<0.05),表明睡眠剥夺组的小鼠空间记忆存在障碍,本实验造模成功。由结果可知,灌胃八肽组的小鼠其逃避潜伏期和总路程相较于模型组均有明显降低,说明八肽的摄入可以显示改善睡眠剥夺诱导的小鼠空间记忆障碍。
表2八肽对睡眠剥夺诱导记忆障碍小鼠空间探索能力的影响
#代表与对照组比较,p<0.05。*表示与模型组比较,p<0.05。
由表2可知,相较于对照组,模型组的小鼠穿越平台次数和平台周围活动时间和距离均显著降低(p<0.05),表明睡眠剥夺组的小鼠空间记忆存在障碍。然而,灌胃八肽组的小鼠其上述指标均得到明显改善,且相比模型组存在显著性差异,表明八肽的摄入可以显示改善睡眠剥夺诱导的小鼠空间记忆障碍。
综上所述,本发明的八肽WCPFSRSF不仅具有神经保护作用,还可以改善谷氨酸诱导的细胞存活率下降和氧化应激水平上升,而且对睡眠剥夺诱导的小鼠记忆障碍也具有一定的改善作用。
实施例7八肽的体外模拟胃肠道消化特性及其对神经保护作用的影响
采用INFOGEST静态体外模拟胃肠道消化评估八肽的胃肠道消化特性。制备模拟胃液(SGF)和模拟肠液(SIF)。将SGF和CaCl2(0.3M)与样品混合均匀,置于锥形瓶中。将混合物的pH值调节至3.0,并添加胃蛋白酶(终酶活为2000U/mL),并重新校正pH值,将锥形瓶置于37℃的恒温水浴摇床中振荡孵育2小时,取样。随后,将混合物的pH调节至7.0,并通过向混合物中加入SIF和CaCl2进行肠消化。添加胰酶(终酶活为100U/mL)和胆汁(10mM)启动肠道消化,并将混合物置于恒温水浴摇床中振荡孵育2小时,然后在90℃加热10分钟以灭活酶,收集样品。采用UPLC-MS/MS进行进一步分析。
由图5和图6的UPLC-MS/MS分析结果可知,八肽经体外模拟胃肠道消化后被降解,说明本发明八肽对于胃蛋白酶和胰蛋白酶不具有抗消化特性。随后,探究胃肠道消化前后的样品对谷氨酸诱导的神经细胞损伤的影响,结果如图7所示。由图可知,多肽经体外模拟胃消化后的活性有所降低,且仅在采用高浓度多肽处理细胞的情况下较为显著,低浓度情况下活性变化并无显著性差异。与胃消化的样品相比,进一步体外模拟肠道消化后的多肽并无显著差异,说明胃消化阶段可能是导致八肽活性降低的主要原因。
实施例8
一种改善记忆的片剂:取以下活性组分:本发明八肽、磷脂酰胆碱、大豆磷脂、茶叶提取物、DHA、加入适量调味剂、辅料或赋形剂,制成片剂。其中,八肽的含量为100mg/片。每日一次,每次两片,用于改善记忆。
实施例9
一种改善记忆的胶囊:取以下药物组分:本发明八肽、大豆卵磷脂、维生素E、维生素D、鱼油、乳清蛋白,加入适量的辅料,制成胶囊。口服,每日一次,每次1-2粒。
实施例10
一种改善记忆肽微胶囊的制备方法:采用麦芽糊精和明胶作为壁材,将麦芽糊精(15%,w/w)过夜磁力搅拌使其分布均匀,制备明胶溶液(9%,w/w)并混合均匀,采用磁力搅拌将麦芽糊精溶液与和明胶溶液等比例混合均匀,将改善记忆肽按照壁材:芯材质量比为5:1的比例充分分散于混合液中,并继续磁力搅拌直至均匀,得到混合液1。随后,将混合液1置于冰浴中超声30min,功率为700W。随后采用冷冻干燥或喷雾干燥,得到改善记忆肽微胶囊。
实施例11
一种改善记忆肽微胶囊的制备方法:分别制备2%(w/w)的海藻酸钠溶液和2%(w/w)的抗性淀粉溶液,将其按照等比例混合均匀,得到混合液1。将改善记忆肽溶于水后,逐滴滴入混合液1,并搅拌0.5h后得到混合液2。随后将0.5倍的壳聚糖溶液(0.25g/mL)加入到混合液2中,再搅拌1h,得到混合液3。制备2%(w/w)的氯化钙溶液,使用注射器将混合液3按照1:4的比例缓慢加入氯化钙溶液中,使其凝固0.5h形成胶珠,将胶珠通过离心和水洗后,经冷冻干燥后得到改善记忆肽微胶囊。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (8)
1.一种八肽,其特征在于氨基酸序列为Trp-Cys-Pro-Phe-Ser-Arg-Ser-Phe(WCPFSRSF)。
2.权利要求1的多肽在制备改善记忆的药品和保健品中的应用。
3.根据权利要求2所述的应用,其特征在于:所述的改善记忆,是指缓解神经细胞氧化应激相关症状。
4.根据权利要求2所述的应用,其特征在于:所述改善记忆的药物和保健品还含有其他活性组分和辅料。
5.根据权利要求4所述的应用,其特征在于:所述的其他活性组分包括植物提取物、维生素类、多酚类、鱼油、多不饱和脂肪酸类、乳制品及提取物、微量元素、磷脂类。
6.根据权利要求2所述的应用,其特征在于:所述的药物和保健品是饮料、口服液、胶囊、微胶囊、片剂、粉剂、颗粒剂或悬混剂。
7.根据权利要求6所述的应用,其特征在于:所述的微胶囊包括芯材和壁材,芯材与壁材的质量比为1:(4-10)。
8.根据权利要求7所述的应用,其特征在于:所述壁材的材料包括壳聚糖、瓜儿多胶、麦芽糊精、明胶、阿拉伯胶、果胶、β-环糊精、海藻酸盐、乳清蛋白、磷脂、羧甲基纤维素、氯化钙的一种或多种。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110773378.5A CN113402587B (zh) | 2021-07-08 | 2021-07-08 | 一种八肽及其在制备改善记忆的药品中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110773378.5A CN113402587B (zh) | 2021-07-08 | 2021-07-08 | 一种八肽及其在制备改善记忆的药品中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113402587A true CN113402587A (zh) | 2021-09-17 |
CN113402587B CN113402587B (zh) | 2022-05-10 |
Family
ID=77685655
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110773378.5A Active CN113402587B (zh) | 2021-07-08 | 2021-07-08 | 一种八肽及其在制备改善记忆的药品中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113402587B (zh) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090305946A1 (en) * | 2006-03-31 | 2009-12-10 | The Regents Of The University Of California | Methods and compositions for treating neurodegenerative disorders and alzheimer's disease and improving normal memory |
CN109134612A (zh) * | 2018-09-27 | 2019-01-04 | 广东华肽生物科技有限公司 | 一种改善记忆的五肽及其用途 |
CN109265514A (zh) * | 2018-09-28 | 2019-01-25 | 华南理工大学 | 一种抗胃肠道消化的改善记忆肽及其用途 |
-
2021
- 2021-07-08 CN CN202110773378.5A patent/CN113402587B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090305946A1 (en) * | 2006-03-31 | 2009-12-10 | The Regents Of The University Of California | Methods and compositions for treating neurodegenerative disorders and alzheimer's disease and improving normal memory |
CN109134612A (zh) * | 2018-09-27 | 2019-01-04 | 广东华肽生物科技有限公司 | 一种改善记忆的五肽及其用途 |
CN109265514A (zh) * | 2018-09-28 | 2019-01-25 | 华南理工大学 | 一种抗胃肠道消化的改善记忆肽及其用途 |
Non-Patent Citations (1)
Title |
---|
QI ZHANG等: "Neuroprotection of round scad (Decapterus maruadsi) hydrolysate in glutamate-damaged PC12 cells: Possible involved signaling pathways and potential bioactive peptides", 《JOURNAL OF FUNCTIONAL FOODS》 * |
Also Published As
Publication number | Publication date |
---|---|
CN113402587B (zh) | 2022-05-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20230233672A1 (en) | Methods of manufacture of nut flours and formulations for oral immunotherapy | |
US7151088B2 (en) | Neuroprotective dietary supplement | |
WO2017124921A9 (zh) | 一种核桃低聚肽粉及其制备方法和用途 | |
US20080014270A1 (en) | Methods for improved lipid metabolism and basal metabolic rate with lactoferrin | |
US20190314425A1 (en) | Akkermansia muciniphila strain having a prophylactic or therapeutic effect on a degenerative brain disease or metabolic disease and use thereof | |
NO334587B1 (no) | Anvendelse av glycosider av diacylglycerol som anti-inflammatoriske midler. | |
JP2009520470A (ja) | 新規の乳酸桿菌株及びその使用 | |
TW201304768A (zh) | 使用β-羥基-β-丁酸甲酯促進廢用一段時期後肌肉恢復的方法 | |
US20130189382A1 (en) | Use of fucoxanthin in the preparation of product for improving memory and having neuroprotective effect associated with neurodegenerative disorder | |
US20200000857A1 (en) | Flowable concentrated phospholipid krill oil composition | |
BR102018016746A2 (pt) | Composição farmacêutica para prevenção de obesidade induzida por dieta | |
JP2018524286A (ja) | 動物脳抽出物を調製するためのプロセス | |
WO2019037682A1 (zh) | 用于调整肠道菌群的肠溶氧气微囊及其制备方法与用途 | |
CN106974262A (zh) | 肠道益生杆菌在治疗和预防肥胖及其相关疾病中的应用 | |
Ding et al. | Peanut meal extract fermented with Bacillus natto attenuates physiological and behavioural deficits in a D-galactose-induced ageing rat model | |
CN113402587B (zh) | 一种八肽及其在制备改善记忆的药品中的应用 | |
JP4040069B2 (ja) | 脳機能改善用組成物 | |
CN116751727A (zh) | 一种改善帕金森病的长双歧杆菌婴儿亚种及其应用 | |
RU2762824C1 (ru) | Комбинация для снижения окислительного стресса в организме и поддержания функций печени | |
CN114794491A (zh) | 一种改善脑功能的组合物及其制备方法 | |
CN113754719B (zh) | 三肽及其在制备改善记忆的药品和保健品中的应用 | |
Hu et al. | Prophylactic effect of Lactobacillus fermentum TKSN02 on gastric Injury Induced by Hydrochloric Acid/Ethanol in mice through its antioxidant capacity | |
KR20190003570A (ko) | 안전한·안정된 플라스마로겐과 그 제제 및 인지증의 미병 상태의 판정 방법 | |
Olawale et al. | Comparative histoarchitectural and biochemical studies of the hippocampus in peroxisome proliferative activated receptor gamma agonist treated insulin resistant rats | |
TW202430200A (zh) | 改善認知功能的組合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |