CN102370675A - 大叶冬青提取物为有效成分的药物组合物 - Google Patents
大叶冬青提取物为有效成分的药物组合物 Download PDFInfo
- Publication number
- CN102370675A CN102370675A CN2011102322684A CN201110232268A CN102370675A CN 102370675 A CN102370675 A CN 102370675A CN 2011102322684 A CN2011102322684 A CN 2011102322684A CN 201110232268 A CN201110232268 A CN 201110232268A CN 102370675 A CN102370675 A CN 102370675A
- Authority
- CN
- China
- Prior art keywords
- extract
- ilicis rotundae
- cortex ilicis
- disease
- cortex
- 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
- 239000000284 extract Substances 0.000 title claims abstract description 79
- 244000078118 Ilex latifolia Species 0.000 title claims abstract description 12
- 235000008706 Ilex latifolia Nutrition 0.000 title claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
- 239000004480 active ingredient Substances 0.000 title abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 49
- 206010008118 cerebral infarction Diseases 0.000 claims abstract description 37
- 210000004556 brain Anatomy 0.000 claims abstract description 36
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 36
- 239000000203 mixture Substances 0.000 claims abstract description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 22
- 206010027175 memory impairment Diseases 0.000 claims abstract description 17
- 208000023589 ischemic disease Diseases 0.000 claims abstract description 14
- 230000036541 health Effects 0.000 claims description 23
- 239000004615 ingredient Substances 0.000 claims description 19
- 230000007850 degeneration Effects 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 235000013376 functional food Nutrition 0.000 claims description 15
- 230000002265 prevention Effects 0.000 claims description 15
- 206010012289 Dementia Diseases 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 7
- 208000006011 Stroke Diseases 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 201000006474 Brain Ischemia Diseases 0.000 claims description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 5
- 206010039966 Senile dementia Diseases 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 230000006872 improvement Effects 0.000 claims description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 3
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 3
- 208000024571 Pick disease Diseases 0.000 claims description 3
- 238000002347 injection Methods 0.000 abstract description 29
- 239000007924 injection Substances 0.000 abstract description 29
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 abstract description 12
- 239000004220 glutamic acid Substances 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 9
- 230000036542 oxidative stress Effects 0.000 abstract description 9
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 abstract description 8
- 230000034994 death Effects 0.000 abstract description 8
- 235000013922 glutamic acid Nutrition 0.000 abstract description 8
- 210000002569 neuron Anatomy 0.000 abstract description 7
- 102000013455 Amyloid beta-Peptides Human genes 0.000 abstract description 6
- 108010090849 Amyloid beta-Peptides Proteins 0.000 abstract description 6
- 235000013402 health food Nutrition 0.000 abstract description 6
- 206010030113 Oedema Diseases 0.000 abstract description 5
- 206010029350 Neurotoxicity Diseases 0.000 abstract description 4
- 206010044221 Toxic encephalopathy Diseases 0.000 abstract description 4
- 231100000228 neurotoxicity Toxicity 0.000 abstract description 4
- 230000007135 neurotoxicity Effects 0.000 abstract description 4
- 208000014644 Brain disease Diseases 0.000 abstract 2
- 230000003412 degenerative effect Effects 0.000 abstract 2
- 230000001054 cortical effect Effects 0.000 abstract 1
- 230000002461 excitatory amino acid Effects 0.000 abstract 1
- 239000003257 excitatory amino acid Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 35
- 238000004519 manufacturing process Methods 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 23
- 210000003710 cerebral cortex Anatomy 0.000 description 17
- 241000699666 Mus <mouse, genus> Species 0.000 description 16
- 238000000034 method Methods 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 14
- 206010021143 Hypoxia Diseases 0.000 description 13
- 230000007954 hypoxia Effects 0.000 description 13
- 230000001939 inductive effect Effects 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000000605 extraction Methods 0.000 description 11
- 230000004083 survival effect Effects 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 210000001367 artery Anatomy 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 230000030833 cell death Effects 0.000 description 9
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 8
- 235000013361 beverage Nutrition 0.000 description 8
- 206010048962 Brain oedema Diseases 0.000 description 7
- 201000004810 Vascular dementia Diseases 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 208000006752 brain edema Diseases 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 231100000167 toxic agent Toxicity 0.000 description 7
- 239000003440 toxic substance Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 210000004958 brain cell Anatomy 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 208000028867 ischemia Diseases 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 230000001537 neural effect Effects 0.000 description 6
- -1 oxidative stress Substances 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000002481 ethanol extraction Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- 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 4
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 4
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 239000000470 constituent Substances 0.000 description 4
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
- 230000003203 everyday effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 229940041476 lactose 100 mg Drugs 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 206010003062 Apraxia Diseases 0.000 description 2
- 241000209034 Aquifoliaceae Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010008088 Cerebral artery embolism Diseases 0.000 description 2
- 206010008132 Cerebral thrombosis Diseases 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- 208000005189 Embolism Diseases 0.000 description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 238000012347 Morris Water Maze Methods 0.000 description 2
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000001435 Thromboembolism Diseases 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 206010072731 White matter lesion Diseases 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 229940039856 aricept Drugs 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
- 229940093471 ethyl oleate Drugs 0.000 description 2
- 230000002964 excitative effect Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 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 2
- 239000008187 granular material Substances 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 210000002425 internal capsule Anatomy 0.000 description 2
- 201000010849 intracranial embolism Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 210000001161 mammalian embryo Anatomy 0.000 description 2
- 239000000401 methanolic extract Substances 0.000 description 2
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 238000011302 passive avoidance test Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000002360 prefrontal effect Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 2
- 229960001685 tacrine Drugs 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010050012 Bradyphrenia Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 206010008092 Cerebral artery thrombosis Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000037451 Leukoaraiosis Diseases 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 206010053648 Vascular occlusion Diseases 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 201000008247 brain infarction Diseases 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000001159 caudate nucleus Anatomy 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 229940069647 citric acid 1000 mg Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 210000003017 ductus arteriosus Anatomy 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940108366 exelon Drugs 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- WPFVBOQKRVRMJB-UHFFFAOYSA-N hydroxycitronellal Chemical compound O=CCC(C)CCCC(C)(C)O WPFVBOQKRVRMJB-UHFFFAOYSA-N 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 235000008446 instant noodles Nutrition 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004900 laundering Methods 0.000 description 1
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 210000000478 neocortex Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001107 psychogenic effect Effects 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 229960003946 selegiline Drugs 0.000 description 1
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000036967 uncompetitive effect Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000008979 vitamin B4 Nutrition 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 229940033203 vitamin b6 0.5 mg Drugs 0.000 description 1
- 235000008939 whole milk Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- 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)
-
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Medical Informatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Microbiology (AREA)
- Nutrition Science (AREA)
- Biomedical Technology (AREA)
- Polymers & Plastics (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
本发明涉及一种以大叶冬青(Ilex latifolia)提取物为有效成分的缺血性疾病或退行性脑疾患的预防或治疗用成分,具体而言,水、酒精或水和酒精的混合物作为溶媒提取的大叶冬青提取物在诱发脑梗塞的大鼠身上抑制了脑梗塞和浮肿,在注射β-淀粉样蛋白[amyloidβprotein;Aβ(25-35)]诱发神经毒性的老鼠身上抑制了记忆损伤,且确认了根据注射量可以抑制过氧化氢(H2O2)诱发的氧化应激、兴奋性氨基酸-谷氨酸、诱发神经毒性的Aβ(25-35)以及低氧症诱导的大脑皮质神经细胞的死亡等。因此,本发明的大叶冬青提取物可以作为缺血性疾病或退行性脑疾患的预防或治疗用的药品成分或保健功能食品的有效成分使用。
Description
技术领域
本发明涉及一种缺血性疾病或退行性脑疾患的预防或治疗用药物组合物,具体而言,作为有效成分含有植物提取物。
背景技术
缺血性脑中风(cerebral apoplexy),即,脑梗塞(cerebral infarction)的主要病因是血管动脉硬化症引起的脑动脉血栓或栓塞和心脏疾病等引发的心因性栓塞。脑血管堵住引发的脑梗塞症又分为脑血栓症和脑栓塞症。脑血栓症是高血压、糖尿病、高血脂症等引发动脉硬化,动脉管壁变厚或变硬,由此造成血管变窄,血管内壁容易受损不光滑,血流不顺畅,导致血液供应显著降低或中断,脑细胞得不到氧气和营养物质,导致脑功能障碍。脑栓塞症是心瓣膜病或心房颤动等疾病导致心脏内的血流出现异常,部分血液滞留在心脏内凝固,产生血液残渣。脱落的血液残渣堵塞脑血管引发脑梗塞。
血管性痴呆(vascular dementia)是由于脑血管疾病导致脑损伤而发生的后天性不可逆转性认知功能的降低。脑中风和脑梗塞引发的痴呆占全部痴呆症的三分之一左右,是继老年痴呆症之后发病频率高的痴呆。与一般的脑中风和脑梗塞一样,高龄、吸烟等具有血管性危险因素的患者容易产生脑部大血管或小血管闭塞,由此大脑皮质或皮质下方的联合神经纤维遭到破坏,发生血管性痴呆。血管性痴呆根据构成病因的血管病理或产生痴呆的病变位置,可以分为多发性脑梗塞痴呆(multi-infarct dementia)、皮质下缺血性血管性痴呆(subcortical ischemic vascular dementia)以及闭塞导致的单一病变性痴呆(strategic infarct dementia)等。其中,闭塞导致的单一病变性痴呆是尾状核(caudate nucleus)、内侧额叶(mesial frontal lobe)、内囊膝(genu of internal capsule)等发生的单一病变导致的痴呆。小血管疾病引发的裂孔性脑梗塞或不完全硬塞引发的脑白质疏松(leukoaraiosis;white matter hyperintensity)主要损伤前额叶-皮质下回路(prefrontal-subcortical circuit)。可能出现的症状不是 记忆障碍等传统的痴呆症状,而是智力迟钝(bradyphrenia)、失用症(apraxia)等皮质下症状(subcorticaldysfunctio)。
老年痴呆症(AD;Alzheimer′s disease)的特征是神经细胞(neuron)的丧失和源于淀粉质前躯体蛋白质的39-43氨基酸肽-淀粉样蛋白(amyloid-beta;Aβ)为主要构成成分的细胞外老年斑(senile plaque)。试管以及生物体内研究结果表明,Aβ或Aβ缩氨酸单片具有毒性效果,启示Aβ对AD的发病起到重要的作用(Butterfield et al.,Free Radical Biology and Medicine,2002,32:1050-1060;ButterfIeld et al.,Free Radical Biology and Medicine,2007,43:658-677)。培养时,Aβ会直接诱导神经细胞的死灭,使神经细胞对兴奋毒性以及氧化性损伤脆弱。NMDA(N-methyl-D-aspartate receptor)受体承担Aβ结合的选择性基质或Aβ-诱发的谷氨酸兴奋毒性的媒介作用。NMDA受体尤其是对Ca2+具有高度透过性的配体-门控/伏特-敏感性阳离子通道,。[Ca2+]i的大范围的上升会直接导致细胞功能不振、过度兴奋或死灭。因此,如同Aβ的神经毒性效果被非竞争性NMDA受体拮抗剂(5R.10S)-(+)-5-甲基-10,11-脱氢-5H-吩噻恶[a,d]Cyclo hepten-5,10-Imine maleate(MK-801)[5R.10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,b)cyclohepten-5,10-imine maleate]减少的报告所证明,Aβ曝光方式的通过NMDA受体的Ca2+引入对Aβ-诱导的神经毒性中起到决定性作用。相信活性氧(ReactiveOxygen species;ROS)的形成也干预到退行性脑疾患的发病。几项证据证明通过妨碍神经细胞恒定性的广泛的分子形状,促发神经退化或使之更加容易,Aβ-媒介的神经病中作为活性因子衬托氧化应激的干预。但是,NMDA受体拮抗剂和神经细胞通道的直接阻断剂的临床有益性由于缺乏可确认的效能或具有严重的副作用。
大部分的退行性脑疾患伴随着痴呆,尤其,认知障碍和记忆障碍(记忆力衰退)。因此,包括痴呆在内的退行性脑疾患的比较理想的治疗药物应该是延迟脑细胞的破坏和老化,保护脑细胞,恢复认知功能。目前为止开发的药剂有,抑制活性氧对脑细胞的破坏性的维生素E和司立吉林(selegiline)等抗氧化剂、塔克林(Tacrine)、安理申(Aricept)以及艾斯能(Exelon)等乙酰胆素分解酶抑制剂(acetylcholinesterase-inhibiting drugs)等。但是,这些药剂都诱发相当大的副作用,且其效能并不突出。
属于冬青科(Aquifoliaceae)的大叶冬青(I.latifolia)分布在中国和越南等地,是中国南部居民喜欢饮用的苦丁茶(Ku ding cha)的主要原料。传统医学 中苦丁茶用于头痛、高血压等的治疗剂,尤其,大叶冬青用于缺血性心脏疾病以及心肌梗塞的治疗剂。但是,实际上还没有证实过大叶冬青对退行性脑疾患的治疗效果。
因此,本发明人为了开发对脑血管疾患具有预防和疗效的天然物质而努力的过程中,发现了大叶冬青提取物在诱发脑梗塞的大鼠身上抑制脑梗塞以及浮肿,注射Aβ(25-35)诱发神经毒性的老鼠身上抑制记忆的损伤,且根据注射量还可以抑制,过氧化氢(H2O2)诱发的氧化应激、谷氨酸以及Aβ(25-35)等毒性物质以及低氧症诱导的大脑皮质神经细胞的死亡,由此确认本发明的大叶冬青提取物可以用于脑血管疾病的预防或治疗用药物成分以及保健功能食品的有效成分,完成了本发明。
发明内容
本发明的旨在于,提供将大叶冬青(Ilex latifolia)提取物作为有效成分的缺血性疾病或退行性脑疾患的预防或治疗用药物组合物以及保健功能食品。
本发明的另一个旨在于,提供将大叶冬青提取物作为有效成分的记忆损伤改善用药物组合物以及保健功能食品。
为了实现上述的目的,本发明提供将大叶冬青(Ilex latifolia)提取物作为有效成分的缺血性疾病或退行性脑疾患的预防或治疗用药物组合物以及保健功能食品。
并且,本发明提供将大叶冬青提取物作为有效成分的记忆损伤改善用药物组合物以及保健功能食品。
本发明的大叶冬青(Ilex latifolia)提取物在诱发脑梗塞的大鼠身上抑制脑梗塞以及浮肿,注射Aβ(25-35)诱发神经毒性的老鼠身上抑制记忆损伤,有效抑制过氧化氢(H2O2)诱发的氧化应激、谷氨酸以及Aβ(25-35)等毒性物质以及低氧症诱导的大脑皮质神经细胞的死亡,所以能作为缺血性疾病或退行性脑疾患的预防或治疗用药物成分以及保健功能食品的有效成分使用。
附图说明
图1为大叶冬青(Ilex latifolia)对occlusion/reperfusion引发的脑梗塞的抑制效果(组织学病变)的确认图;
图2为诱发脑梗塞的大鼠身上,确认大叶冬青的脑梗塞以及脑浮肿抑制效果的结果图;
图3为通过Aβ(25-35)诱发神经损伤的老鼠身上,通过大小鼠避暗测试确认记忆损伤抑制效果的结果图;
图4为通过Aβ(25-35)诱发神经损伤的老鼠身上,通过水迷宫测试(Water maze test)确认记忆损伤抑制效果的结果图;
图5为大脑神经细胞上,通过MTT分析表示的过氧化氢诱导的氧化应激对细胞死亡抑制效果的分析图。
图6为通过MTT分析确认,大叶冬青对谷氨酸诱导的大脑神经细胞死亡抑制效果的确认图;
图7为通过MTT分析确认,大叶冬青对Aβ(25-35)诱导的大脑神经细胞死亡抑制效果的确认图;
图8为通过MTT分析确认,大叶冬青对低氧症(Hypoxia)诱导的大脑神经细胞死亡抑制效果的确认图。
具体实施方式
下面结合附图详细说明本发明的具体实施方式。
本发明提供,将大叶冬青(Ilex latifolia)提取物作为有效成分的缺血性疾病或退行性脑疾患的预防或治疗用药物组合物。
并且,本发明提供,将大叶冬青提取物作为有效成分的记忆损伤改善用药物组合物。
大叶冬青可以自由采用人工栽培或市场上销售的。
上述大叶冬青提取物是包括下列步骤的制造方法来制作比较理想,但并不限于此。
依次执行下述步骤可以制作大叶冬青提取物:
1)在大叶冬青添加提取溶媒进行提取的步骤;
2)晾干步骤1)的提取物进行过滤的步骤;以及
3)将步骤2)中过滤的提取物进行回流冷凝后烘干的步骤。
上述提取溶媒最好选用水、酒精或其混合物。上述酒精最好采用C1至C2的低级酒精,当采用乙醇时,比其他溶媒的提取效果更好,所以低级酒精选用乙醇更理想。提取方法上采用振荡提取、索格里特(Soxhlet)提取或回流提取法比较好,但并不限于此。将干燥大叶冬青份量5至15倍的提取溶媒添加进去进行提取比较好,最好的比例是添加大叶冬青份量的十倍。提取温度控制在40-100℃比较好,最好是控制在60-80℃,但并不限于此。并且, 提取时间控制在4-24小时比较好,最好是控制在8-15小时,但并不限于此。与此同时,提取次数控制在1-5次比较好,最好是反复提取三次,但并不限于此。
上述方法上,步骤3)的干燥选用减压干燥、真空干燥、沸腾干燥、喷雾干燥或冻结干燥等比较好,但并不限于此。
上述缺血性疾病或退行性脑疾患最好是脑梗塞、脑缺血、脑中风、痴呆、老年痴呆症、杭廷顿氏舞蹈病、pick病以及克罗伊茨费尔特-雅各布氏病(Creutzfeld-Jakob)病组成的疾病组之一,但并不限于此。
本发明的具体实施方式中,发明人在诱发脑梗塞的大鼠身上确认了大叶冬青提取物对脑梗塞以及浮肿的抑制效果(见图1以及图2、表1)。并且,注射β-淀粉样蛋白[amyloidβprotein;Aβ(25-35)]诱发神经毒性的老鼠身上,通过大小鼠避暗测试(passive avoidance test;Step through)以及水迷宫(Morris water maze)测试,确认了大叶冬青提取物对记忆损伤的抑制效果(见图3以及图4)。
并且,本发明的具体实施方式中,还确认了大叶冬青提取物根据其注射量,对过氧化氢(H2O2)诱发的氧化应激、谷氨酸以及Aβ蛋白质等毒性物质造成的大脑皮质神经细胞的死亡具有抑制效果(见图5至图7)。并且,确认了通过低氧症诱导的大脑皮质神经细胞的死亡,根据大叶冬青提取物的注射量受到抑制(见图8)。
因此,本发明的大叶冬青提取物可以作为脑血管疾患的预防或治疗用,或记忆损伤改善用药物组合物的有效成分使用。
含有本发明大叶冬青提取物的成分占总重量的0.1重量%至50重量%比较合适,但并不限于此。
本发明的成分在临床上被使用时,可以采用口服或非口服的方式,可以作为一般的医药品制剂的形态使用。本发明的成分在实际临床上使用时,可以采用口服以及非口服的各种制形。制作成制剂时,采用通常使用的填充剂、增量剂、湿润剂、崩解剂以及表面活动剂等的稀释剂或赋形剂调制。用于口服的固形制剂包括,片剂、丸剂、散剂、颗粒剂、胶囊剂等,这些固形制剂是本发明的药物成分中至少添加一种以上的赋形剂,比如,淀粉、碳酸钙、蔗糖、乳糖以及凝胶等调制。并且,除了纯赋形剂之外,还使用镁、硬脂酸酯(stearate)、滑石等润滑剂。口服的液状制剂有,悬浮液、内容液状以及糖浆等。除了通常使用的纯稀释剂水、液体蜡之外,可以包括各种赋形剂, 比如,湿润剂、甘味剂、芳香剂、保存剂等。非口服的制剂有,灭菌水溶液、非水性溶剂、悬浮剂、乳剂、冻结干燥剂、佐剂等。非水性溶剂以及悬浮溶剂有,丙二醇、聚乙二醇、橄榄油等植物性油、油酸乙酯(ethyl oleate)等可注射的酯类。作为佐剂的基剂可以采用witepsol、聚乙二醇、tween61、可可豆脂、羟基香茅醛、甘油以及凝胶等。本发明药物组合物的非口服使用方法有,皮下注射、静脉注射或肌肉注射等。
用药单位而言,比如,含有个别用药量的1、2、3或4倍,或可以含有1/2、1/3或1/4倍。个别用药量最好含有有效药物每次口服或注射的量,这相当于通常每日用药量的全部、1/2、1/3或1/4倍。本发明组成物的有效容量为0.0001~10g/kg,最好的用药量为0.0001g~5g/kg,一天可以口服或注射1~6次。
本发明的组成物在脑血管疾病的预防或治疗过程中,可以单独使用,也可以配合手术、激素治疗、化疗以及生物学反应调节剂的其他方法使用。
并且,本发明提供将大叶冬青提取物作为有效成分的缺血性疾病或退行性脑疾患的预防或改善用保健功能食品。
与此同时,本发明提供,将大叶冬青提取物作为有效成分的极易损伤改善用保健功能食品。
本发明的具体实施方式中,发明人在诱发脑梗塞的大鼠身上确认了大叶冬青提取物对脑梗塞以及浮肿的抑制效果(见图1、图2、表1),还在诱发神经毒性的老鼠身上,确认了大叶冬青提取物对记忆损伤的抑制效果(见图3以及图4)。并且,确认了根据大叶冬青提取物的注射量,对氧化应激、毒性物质以及低氧症引发的大脑皮质神经细胞的死亡具有抑制效果(见图5至图8)。
因此,将大叶冬青提取物作为有效成分的本发明药物组合物,可以用于物质缺血性疾病或退行性脑疾患的预防或改善用,或记忆损伤改善用保健功能食品。
本发明的保健功能食品可以直接添加大叶冬青提取物,或与其他食品或食品成分配合使用,按照通常的方法可以合理使用。有效成分的混合量可以根据使用目的(预防、保健或治疗性处置)来决定。一般来讲,制造食品或饮料时,本发明成分对原料的添加比为15重量份以下,最好是10重量份以下的量。但是,以保健以及卫生作为目的或调节身体为目的的长期服用时,摄入量可能比上述范围少,但是由于安全性方面没有任何问题,有效性份可 以超过上述范围以上的量。
上述食品的种类没有特别的限制。可以添加上述物质的食品有,肉类、香肠、面包、巧克力、糖果类、点心类、饼干类、匹萨、方便面、其他面食类、口香糖、冰淇淋在内的乳品、各种汤类、饮料、茶、饮品、酒精饮料以及复合维生素等,包括通常意义上的所有保健食品。
本发明的保健饮料成分可以与普通的饮料一样,含有各种香味剂或天然碳水化合物等。上述的天然碳水化合物有,葡萄糖、果糖等单糖、麦芽糖、蔗糖等二糖类以及葡聚糖、环糊精等多糖、木糖醇、山梨糖醇、赤藓醇等糖乙醇。甘味剂可以选用非洲竹芋甜索、甜菊提取物等天然甘味剂或糖精、阿斯巴甜等合成甘味剂。上述天然碳水化合物的比率而言,本发明成分每100ml含有约0.01~0.04g,最好是含有约0.02~0.03g。
除了上述之外,本发明的大叶冬青提取物可以含有,各种营养剂、维生素、电解质、风味剂、着色剂、果胶酸及其盐、海藻酸及其盐、有机酸、保护性胶体增粘剂、pH调节剂、稳定剂、防腐剂、甘油、酒精、碳酸饮料中使用的碳酸化剂等。除此之外,本发明的大叶冬青提取物可以含有,制造天然果汁、果汁饮料、蔬菜饮料为目的的果肉。可以独立或组合使用这些成分。虽说这些添加剂的比率不太重要,但是通常在本发明的成分每100重量份0.02~1重量份的范围内选择。
本发明的大叶冬青提取物几乎没有毒性和副作用,作为预防目的可以长期服用。
实施例
下面,结合实施例和制造例详细说明本发明。但,下面的实施例和制造例只是本发明的例示,并非本发明内容限定在下面的实施例和制造例。
实施例1大叶冬青(Ilex latifolia)提取物的制造
<1-1>乙醇提取物的制造
大叶冬青是在首尔庆东的中药材市场购买后切碎使用。准备100克大叶冬青后,在室温环境下利用3L的100%乙醇,三个小时内用回流冷凝器中提取了三次。通过沃特曼1号纸过滤上述溶液后烘干,最终收获了乙醇提取物18.7g。最终收获的大叶冬青提取物是放入二甲基亚砜(dimethylsulfoxide;DMSO)内溶解成50mg/ml的浓度,保管在-20℃的环境中。实验时,对实验缓冲液进行稀释,使DMSO的最终浓度达到0.1%一下后使用。
<1-2>水提取物的制造
除了用水作为提取溶媒取代100%乙醇之外,按上述实施例<1-1>的提取方法获得了粉末(收率21.5%)。
<1-3>80%乙醇提取物的制造
除了用80%的乙醇作为提取溶媒取代100%乙醇之外,按上述实施例<1-1>的提取方法获得了粉末(收率20.4%)。
<1-4>100甲醇提取物的制造
除了用100%的甲醇作为提取溶媒取代100%乙醇之外,按上述实施例<1-1>的提取方法获得了粉末(收率19.1%)。
实施例2诱发脑梗塞的大鼠身上,大叶冬青提取物的脑梗塞以及浮肿抑制效果的确认
本发明人为了在诱发脑梗塞的大鼠身上确认大叶冬青提取物的效能,实施了如下的实验。首先,使300±5g的SD大鼠(SAMTAKO,京畿道)吸入1-2%isoflurane(N2∶O2=4∶1)进行麻醉后,通过外科手术小心地曝光出了右侧颈动脉。对大鼠的外径动脉分支到中央部的舌动脉(linguinal artery)和从外颈动脉向内颈动脉分支的甲状腺动脉(thyroid artery),通过电灼进行了结扎。此时,在动脉结扎前30分钟、结扎后一个小时、去除结扎后一个小时后,喂食了大叶冬青提取物(分别50,100或200mg/kg)或作为阳性对照组的MK-801(1mg/kg)。作为阴性对照组使用了未添加任何物质的实验缓冲液(生理食盐水注射液)的注射大鼠。之后,发现内颈动脉上方的Y字形分支为止,清理好周围后,将外颈动脉的头部用线结扎切断血流,并为了防止总颈动脉和内颈动脉之间的血流,用夹子夹住了上下。之后,在总颈动脉打一个小孔插入探针后,用线轻轻结扎探针和外颈动脉的下方部位止血,然后去除了防止血流的夹子。切开插入探针的孔和结扎外颈动脉的部位之间,将插入到外颈动脉的探针小心地挪到内颈动脉插入后,在内颈动脉上方分支为Y字形的血管中,向内侧血管插入了探针。此时,探针从总颈动脉分支只插入了20mm。手术后马上测量直肠温度开始,在6小时内维持了37±0.5℃。结扎(occlusion)2小时后去除探针进行再灌注(reperfusion),然后24小时后使脱骨致死并分离了脑。利用脑基质(Brain matrix)将上述步骤中分离的脑切割成2mm厚度后,利用2%TTC溶液在37℃温度条件下染色30分钟,然后用数码相机拍摄,利用Image analysis system(Optimas 6.1,Media Cybernetics, Silver Springs,美国)测量了梗塞容积和浮肿容积。此时,将赋形液(vehicle)的处理组作为对照组,表1中显示了各提取物的梗塞容积,并将效果最好的乙醇提取物的脑梗塞容积和浮肿容积显示在图1中。
如图1所示,大叶冬青显著降低了,通过缺血/再回流(ischemia/reperfusion)法引发梗塞的大鼠脑组织的梗塞容积和浮肿容积。第一行的脑组织为正常状态下大鼠的脑,没有出现缺血,所以整个脑部都是通红的。第二行图片是未经任何处理的状态下,诱导脑缺血时的照片,脑梗塞在左半球已经生成。与此相比,第三行的脑部图片为分别在动脉结扎前三十分钟、一个小时、以及去除动脉结扎后一个小时内,口服大叶冬青200mg/kg的动物脑部,图中可见,显著抑制了颈动脉结扎诱发的脑缺血引发的脑梗塞。第四行为作为阳性对照组使用的注射MK-801的大鼠脑部照片。
并且,如图2所示,阴性对照组表现出354.3mm3的梗塞容积相比,大叶冬青50mg/kg注射组为166.0mm3、100mg/kg注射组为136.3mm3、200mg/kg注射组为108.3mm3,可见梗塞抑制效果依赖于注射量。并且,赋形液注射组的脑浮肿容积为62.5mm3相比,大叶冬青50mg/kg注射组为40.6mm3、100mg/kg注射组为28.3mm3、200mg/kg注射组为21.8mm3,显著降低了脑浮肿。之后的实验中,只采用脑梗塞抑制效果最好的乙醇水溶液提取物进行了实验。
【表1】
用药量 | 乙醇提取物 | 乙醇水溶液提取物 | 水提取物 | 甲醇提取物 |
阴性对照组 | 360 | 360 | 360 | 360 |
50mg/kg | 170 | 192 | 220 | 230 |
100mg/kg | 135 | 146 | 195 | 173 |
200mg/kg | 103 | 111 | 150 | 132 |
实施例3通过大小鼠避暗测试(passive avoidance test;Step through)的记忆以及学习的测定
实验动物采用了ICR老鼠(BioLink Co.韩国),购买后经过一段时间的适应期后,在实验第一天(0天)喂食了大叶冬青(25、50或100mg/kg),30分钟后使用安装27号nuddle的微细注射器,将15μl(15nmol)的1mM Aβ(25-35)(Bachem,瑞士)慢慢注入到了脑室中(Maurice T et al.,Brain Reserch,1996, 706:181-193)。之后的一个星期之内,每天一次分别喂食25、50以及100mg/kg的大叶冬青提取物,并将动物放置在逐步通过装置(Step through apparatus)(Gemini II avoidance system,Sandiego Instrument)的敞亮的箱子中,进行了三次敞亮区域适用测试。第七天喂食大叶冬青提取物(25、50或100mg/kg),30分钟后将动物放置在敞亮的箱子内,10秒后打开箱门,当动物进入暗箱时门被关闭同时施加电击(0.2mA,2sec),让上述的老鼠熟悉了单一-跟踪逐步通过被动回避实验(One trail step through passive-task)。上述的被动回避箱为断头台型门,分为格子地板和冲击生成器两个区域(各25(W)×21(D)×19(H)cm)。在昏暗的条件下将老鼠放在起始点,50秒后开灯并开门,当老鼠进入暗箱时门被关闭并施加电击(0.2mA,2秒),让动物记住了暗箱内的电击体验。24小时后,将动物置于敞亮箱内进行相同的实验时,记住前一天电击的动物没有移动到暗箱。测量动物在亮箱中的逗留时间,作为记忆形成的指标,逗留时间达到5分钟以上的视为5分钟。
其结果,如图3所示,将Aβ(25-35)(15nmol)注射到脑室,一个星期后进行被动回避实验时,未注射的试验组在259秒后移动到暗处相比,Aβ(25-35)注射组在30秒后移动到了暗处。这意味着没有形成记忆。与此相比,一个星期内每天喂食大叶冬青提取物25、50以及100mg/kg的试验组,随着喂食量的增加,移动到暗箱的时间延长,25mg/kg喂食组为70秒、50mg/kg喂食组为197秒、100mg/kg喂食组为238秒,所有试验组的逗留时间均呈现有意义的增加,确认了Aβ(25-35)导致的记忆损伤抑制功能。
实施例4通过水迷宫测试(Morris water maze)的记忆和学习的测定
将直径90cm、深度40cm的圆形水槽进行四等分,在其中的一个区内设置了高20cm的平台。水温控制在20℃,水位高出平台1.5cm后,用全脂奶粉使水浑浊,这样在水面上就看不到平台。将老鼠分为任意的试验组后,每隔一个小时在四个区域实施使老鼠在每个区域都游泳一次后找到平台的实验(pretest),测定了其时间(prevalue)。最长的游泳时间控制在2分钟,当找不到平台时人为地将老鼠放在平台一分钟。第二天,与被动回避实验中一样,在老鼠的脑室内注射15nmol的Aβ(25-35)(0day),对照组注射了灭菌生理食盐水。大叶冬青提取物是注射Aβ(25-35)之日起每天口服一次,直到水迷宫测试结束。注射Aβ(25-35)后,第四天至第八天(4day-8day)内每天与 pretest相同的方法,测量各老鼠每隔一个小时四次找到平台的时间,取得平均值(latency time)后测量了记忆形成程度。
其结果,如图4所示,比较所有组的注射Aβ(25-35)(15nmol)前的值(第0天)和注射后实验第五天的值时,对照组为116.2->27.9秒形成了记忆,但是只注射Aβ(25-35)的组为114.8->116.1秒没有形成记忆。与此相比,五天喂食大叶冬青提取物的组而言,25mg/kg喂食组为114.5->76.5秒、50mg/kg喂食组为113.2->35秒、100mg/kg喂食组为105.0->62.5秒,所有喂食组都形成记忆,确认了对Aβ(25-35)所导致记忆损伤的抑制效果。50mg/kg喂食组的抑制效果最为突出。
实施例5经过毒性物质处理的大脑皮质神经细胞中,大叶冬青提取物对细胞生存率的效果确认
<5-1>大脑皮质神经细胞的培养
初始(Primary)的大脑皮质神经细胞是15-16天龄的SD白化大鼠(Spragu e-Dawley)胚胎中,通过已知的方法准备的(Ban JY et al.,Life science,2006,79:2251-2259)。对怀孕15天的大鼠进行乙醚麻醉后去除胚胎,在显微镜下只分离了大脑皮质。将大脑皮质放入含有胰蛋白酶(0.25mg/ml)的JMEM(Joklik-modified Eagle′s medium)中,利用5ml滴管进行机械分散后,在37℃条件下培养10分钟,实施了酶分离。对上述的细胞悬浮液以1,500rpm的转速进行五分钟的离心分离后,在所获得的含细胞的沉淀层内添加,含有碳酸氢钠(sodium bicarbonate;44mM)、盘尼西林(40U/ml)、庆大霉素(gentamicin;50g/ml)、KCl(5mM)以及10%胎牛血清(fetal bovine serum)的DMEM,将细胞浓度调整为2×106cells/ml,流经尼龙筛网(nylon mesh;35μm)后植入到事先用多聚赖氨酸(poly-L-lysine)涂层的培养容器中。在维持37℃、5%CO2/95%氮条件的CO2培养基中进行了培养。
<5-2>大叶冬青提取物抑制神经细胞死亡的效果测定
本发明人为了确认实施例1中获取的大叶冬青的混合提取物对神经细胞死亡产生的影响,实施了下列实验。此时,将实施例5-2中准备的大脑皮质神经细胞在培养第3-4天时用于实验。对上述的神经细胞未经任何处理,或分别用10、50以及100μg/ml的上述实施例1中获取的大叶冬青提取物进行了处理。处理15分钟后,为了诱导神经细胞毒性,使用在无血清DME培养基(Serum free Dulbecco′s modified Eagle′s medium;DMEM)中溶解的10μM Aβ(25-35)(Bachem,瑞士)处理上述的神经细胞后,在37℃条件下培养了36小时(Aβ单独处理组以及Aβ+大叶冬青提取物处理组)。之后,用已知的方法进行了MTT分析[3-(4,5-dimethylthiazol-2-yl-2,5-diplenyltetrazolium bromide;MTT)]。(Ban JY et al.,2006).
这种方法是对细胞的生存、增殖进行量化测定的非常精细和稳定的方法,在活细胞内将黄色的水溶性基质MTT转换为深蓝色有色甲(formazan)的线粒体活性作为其依据。因此,所生成的有色甲的量与活细胞的数量成比例。吸光度越高,活细胞越多。去除药物处理后经过24小时培养的细胞培基后,添加MTT(0.5mg/ml)溶液在37℃条件下培养了4个小时。以后,去除MTT溶液,将200μl的acid-isopropanol(0.04N HCl in isopropanol)添加到所有well中,溶解所形成的深蓝色有色甲结晶后,通过microelisa reader测量波长570nm(参照波长630nm)测定了吸光度。此时,将未经药物处理的细胞作为对照组(control),该对照组作为100%时,利用各毒性物质[hydrogen peroxide(H2O2)、兴奋性氨基酸-谷氨酸以及amyloidβprotein单独处理的细胞组以及利用毒性物质和大叶冬青一起处理的细胞组的吸光度显示为%。此时,过氧化氢是为了说明Ischemia性脑损伤,施加氧化应激为目的使用的。
其结果,如图5所示,与对照组(100%)相比,添加过氧化氢的神经细胞诱发了呈现58.4%生存率的细胞死亡,10μg/ml大叶冬青呈现67.4%、50μg/m呈现83.5%、100μg/m呈现105.9%的细胞生存率。由此可见,大叶冬青对氧化应激性脑神经细胞的死亡具有抑制效果。
并且,如图6所示,向大脑皮质脑细胞添加谷氨酸(500μM)后呈现的神经细胞死亡中,对大叶冬青的抑制效果进行分析的结果,与对照组(100%)相比,谷氨酸处理组呈现出了67.7%的生存率。与此相比,大叶冬青1μg/ml呈现72.0%、10μg/ml呈现79.1%、50μg/ml呈现了80.54%的细胞生存率。我们知道脑梗塞的退行性脑疾患中,大量游离兴奋性氨基酸-谷氨酸引发神经细胞死亡。即,大叶冬青可以有效抑制谷氨酸引发的细胞死亡。
与此同时,如图7所示,将Aβ(25-35)注射到老鼠的脑室引发记忆损伤时,口服大叶冬青慢行用药可以抑制记忆损伤。因此,作为探明生化学原理的实验,培养大脑皮质神经细胞,诱发10μM Aβ(25-35)造成的细胞死亡,并分析大叶冬青对此的抑制效果,发现用10μM Aβ(25-35)处置时,与对照组(100%)相比呈现出69.3%的细胞生存率。用大叶冬青处理培养神经细胞时,1、10以及50μg/ml中分别恢复了84.3、88.0以及93.4%的生存率。
实施例6诱发低氧症(Hypoxia)的大脑皮质神经细胞中,大叶冬青提取物对细胞生存率所产生效果的确认
所培养的大脑皮质神经细胞在培养第三天,将培基更换成glucose-freeHEPES缓冲液之后,放入维持2%O2、5%CO2的低氧性chamber well plate内,在chamber内培养了24小时。之后,将培基更换为serum-free DMEM,在5%CO2培养基中再培养6小时,并通过MTT分析测定了细胞生存率。作为对照组,将利用Serum-free DMEM以及glucose-free HEPES缓冲液置换的细胞,放在5%CO2培基内曝光了相同时间。并且,为了满足贫血(ischemia)的条件,将培养的大脑皮质神经细胞放入制造低氧症(hypoxia)条件的chamber内诱发细胞死亡,并分析了大叶冬青对此的抑制效果。
其结果,如图8所示,在低氧症条件下呈现了58.2%的细胞生存率。分别投入10、50以及100μg/ml的大叶冬青提取物时,分别呈现出82.3、90.8以及91.3%的脑细胞生存率,确认了根据大叶冬青提取物的投入量,对低氧症引发的细胞死亡具有抑制效果。
制造例1药物制剂的制造
<1-1>散剂的制造
本发明的大叶冬青提取物300mg
乳糖100mg
滑石10mg
混合上述成分后填充到气密布制造散剂。
<1-2>片剂的制造
本发明的大叶冬青提取物50mg
玉米淀粉100mg
乳糖100mg
硬脂酸镁2mg
混合上述的成分后,按照通常的片剂制造方法打锭制造片剂。
<1-3>胶囊剂的制造
本发明的大叶冬青提取物50mg
玉米淀粉100mg
乳糖100mg
硬脂酸镁2mg
按照通常的胶囊剂的制造方法混合上述成分后,填充到凝胶胶囊制造胶囊剂。
<1-4>注射剂的制造
本发明的大叶冬青提取物50mg
适量注射用灭菌蒸馏水
适量pH调节剂
按照通常的注射剂制造方法,按上述成分含量每ample(2ml)的方法制造。
<1-5>糖浆的制造
本发明的大叶冬青提取物1,000mg
白糖20g
异构化糖20g
适量柠檬香
添加纯净水勾兑出1000ml。按照通常的糖浆制造方法混合上述成分后,填充到褐色瓶,灭菌制造糖浆。
制造例2保健食品的制造
本发明的大叶冬青提取物1,000mg
适量维生素混合物
维生素A醋酸盐70μg
维生素E 1.0mg
维生素B1 0.13mg
维生素B2 0.15mg
维生素B6 0.5mg
维生素B12 0.2μg
维生素C 10mg
生物素10μg
烟酰胺1.7mg
叶酸50μg
泛酸钙0.5mg
适量无机质混合物
硫酸亚铁1.75mg
氧化锌0.82mg
碳酸镁25.3mg
磷酸二氢钾15mg
磷酸氢钙55mg
柠檬酸钾90mg
碳酸钾100mg
氯化镁24.8mg
上述的维生素以及矿物质混合物的配比采用了比较适合保健食品的成分,作为实施例子进行了混合。但是,其配比可以任意变更,按照通常的保健食品制造方法,混合上述的成分后制造颗粒,并按照通常的方法用于保健食品组成物的制造。
制造例3保健饮料的制造
本发明的大叶冬青提取物1000mg
柠檬酸1000mg
低聚糖100g
梅子浓缩液2g
牛磺酸1g
添加纯净水勾兑出900ml
按照通常的保健饮料制造方法,混合上述的成分后,在85℃的条件下搅拌加热1个小时,将制造的溶液进行过滤,用灭菌的2l容器取该溶液后,进行密封灭菌和冷藏保管,然后用于本发明保健饮料的组成物制造。
Claims (10)
1.一种缺血性疾病或退行性脑疾患的预防或治疗用药物组合物,其特征在于,其含有大叶冬青(Ilex latifolia)提取物作为有效成分。
2.一种记忆损伤改善用药物组合物,其特征在于,其含有大叶冬青提取物作为有效成分。
3.根据权利要求1或2所述的药物组合物,其特征在于,所述提取物是以水、酒精或其混合物作为溶媒提取。
4.根据权利要求1或2所述的药物组合物,其特征在于,所述提取物是以乙醇为溶媒提取。
5.根据权利要求1或2所述的药物组合物,其特征在于,所述缺血性疾病为脑梗塞、脑缺血、脑中风组成的疾病组之一,所述退行性脑疾患为痴呆、老年痴呆、杭廷顿氏舞蹈病,pick病以及克罗伊茨费尔特-雅各布氏病(Creutz feld-Jakob)组成的疾病组之一。
6.一种缺血性疾病或退行性脑疾患的预防或改善用保健功能食品,其特征在于,其含有大叶冬青提取物作为有效成分。
7.一种记忆损伤改善用保健功能食品,其特征在于,其含有大叶冬青提取物作为有效成分。
8.根据权利要求6或7所述的保健功能食品,其特征在于,所述提取物以水、乙醇或其混合物作为溶媒提取。
9.根据权利要求6或7所述的保健功能食品,其特征在于,所述提取物以乙醇作为溶媒提取。
10.根据权利要求6或7所述的保健功能食品,其特征在于,所述缺血性疾病为脑梗塞、脑缺血、脑中风构成的疾病组之一,所述退行性脑疾患为痴呆、老年痴呆、杭廷顿氏舞蹈病、pick病以及克罗伊茨费尔特-雅各布氏病(Creutz feld-Jakob)构成的疾病组之一。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510740439.2A CN105311071A (zh) | 2010-08-13 | 2011-08-15 | 大叶冬青提取物为有效成分的药物组合物 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020100078374A KR20120015874A (ko) | 2010-08-13 | 2010-08-13 | 일렉스 라티폴리아 추출물을 유효성분으로 함유하는 허혈성 질환 또는 퇴행성 뇌질환의 예방 또는 치료용 또는, 기억손상 개선용 약학적 조성물 |
KR10-2010-0078374 | 2010-08-13 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510740439.2A Division CN105311071A (zh) | 2010-08-13 | 2011-08-15 | 大叶冬青提取物为有效成分的药物组合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102370675A true CN102370675A (zh) | 2012-03-14 |
CN102370675B CN102370675B (zh) | 2017-06-09 |
Family
ID=45790260
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510740439.2A Withdrawn CN105311071A (zh) | 2010-08-13 | 2011-08-15 | 大叶冬青提取物为有效成分的药物组合物 |
CN201110232268.4A Expired - Fee Related CN102370675B (zh) | 2010-08-13 | 2011-08-15 | 大叶冬青提取物为有效成分的药物组合物 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510740439.2A Withdrawn CN105311071A (zh) | 2010-08-13 | 2011-08-15 | 大叶冬青提取物为有效成分的药物组合物 |
Country Status (5)
Country | Link |
---|---|
JP (1) | JP5358627B2 (zh) |
KR (1) | KR20120015874A (zh) |
CN (2) | CN105311071A (zh) |
HK (1) | HK1223011A1 (zh) |
TW (1) | TWI437998B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020143332A1 (zh) * | 2019-01-10 | 2020-07-16 | 河南中医药大学 | 冬青苷o在制备防治老年痴呆的药物中的应用 |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20150041223A (ko) * | 2013-10-04 | 2015-04-16 | 보령제약 주식회사 | 피마살탄을 포함하는 허혈성 뇌질환 예방 또는 치료용 약학적 조성물 |
KR102099087B1 (ko) | 2018-09-04 | 2020-05-15 | 곽민재 | 탈모방지 또는 발모개선용 조성물 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003113026A (ja) * | 2001-10-05 | 2003-04-18 | Ichimaru Pharcos Co Ltd | リパーゼ活性促進剤 |
JP4544503B2 (ja) * | 2003-04-15 | 2010-09-15 | 株式会社アミノアップ化学 | 雲南苦丁茶成分を含有する組成物 |
CN101099754A (zh) * | 2006-07-07 | 2008-01-09 | 李超生 | 具栖冬青苷的制备方法及应用 |
CN101284031B (zh) * | 2008-06-03 | 2011-05-04 | 上海雷允上科技发展有限公司 | 毛冬青提取物、其制备及应用 |
CN101366738B (zh) * | 2008-10-09 | 2011-05-11 | 河南中医学院 | 毛冬青总黄酮在制备防治短暂脑缺血综合症药物的应用 |
KR101054943B1 (ko) * | 2008-11-14 | 2011-08-05 | 조선대학교산학협력단 | 쿠딩차 추출물로부터 항산화 활성을 갖는 페놀릭 화합물 및이를 유효성분으로 포함하는 기능성식품 |
-
2010
- 2010-08-13 KR KR1020100078374A patent/KR20120015874A/ko not_active Application Discontinuation
-
2011
- 2011-07-25 TW TW100126206A patent/TWI437998B/zh not_active IP Right Cessation
- 2011-08-01 JP JP2011167922A patent/JP5358627B2/ja not_active Expired - Fee Related
- 2011-08-15 CN CN201510740439.2A patent/CN105311071A/zh not_active Withdrawn
- 2011-08-15 CN CN201110232268.4A patent/CN102370675B/zh not_active Expired - Fee Related
-
2016
- 2016-08-01 HK HK16109136.8A patent/HK1223011A1/zh unknown
Non-Patent Citations (2)
Title |
---|
曹健康: "《大叶冬青的开发利用与发展前景》", 《资源开放与市场》, vol. 24, no. 2, 31 December 2008 (2008-12-31), pages 157 - 159 * |
范春林: "《大叶冬青的化学成分研究》", 《中国优秀硕士学位论文医药卫生科技辑》, no. 10, 31 December 2010 (2010-12-31), pages 1 - 7 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020143332A1 (zh) * | 2019-01-10 | 2020-07-16 | 河南中医药大学 | 冬青苷o在制备防治老年痴呆的药物中的应用 |
Also Published As
Publication number | Publication date |
---|---|
CN102370675B (zh) | 2017-06-09 |
CN105311071A (zh) | 2016-02-10 |
TWI437998B (zh) | 2014-05-21 |
JP2012041340A (ja) | 2012-03-01 |
KR20120015874A (ko) | 2012-02-22 |
JP5358627B2 (ja) | 2013-12-04 |
TW201206454A (en) | 2012-02-16 |
HK1223011A1 (zh) | 2017-07-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11771726B2 (en) | Composition, containing Quisqualis indica extract, for preventing or treating prostatic hyperplasia | |
US20140050805A1 (en) | Composition, glucose metabolism-improving agent, and method for improving glucose metabolism | |
CN114502184A (zh) | 防治冠状病毒感染的包括杜英萃取物的药物和食品组合物 | |
WO2016190566A9 (ko) | 아위버섯 물 추출물을 유효성분으로 함유하는 대사성질환의 예방 및 치료용 약학적 조성물 또는 건강기능성식품 | |
JP2012526801A (ja) | 発酵茶抽出物を含有する血液循環改善用組成物、発酵茶抽出物を含む薬剤学的組成物及び健康食品組成物 | |
CN102370675A (zh) | 大叶冬青提取物为有效成分的药物组合物 | |
JPWO2004112817A1 (ja) | セリ科植物由来抽出物およびその製造方法 | |
KR102230517B1 (ko) | 충치 억제 활성을 갖는 락토바실러스 살리바리우스를 포함하는 조성물 | |
US20060110474A1 (en) | Rubrofusarin glycoside-containing composition | |
KR101447121B1 (ko) | 모과 미숙과 추출물을 유효성분으로 함유하는 크산틴 산화효소 저해용 조성물 또는 건강기능식품 | |
KR102210092B1 (ko) | 충치 억제 활성을 갖는 락토바실러스 루테리 mg505 를 포함하는 조성물 | |
KR101793145B1 (ko) | 가시박 추출물 또는 이의 분획물을 유효성분으로 포함하는 대사성 질환의 예방 또는 치료용 조성물 | |
KR102380295B1 (ko) | 귀리 추출물을 포함하는 근감소증 예방, 개선 또는 치료용 조성물 | |
JP2021500382A (ja) | 非アルコール性脂肪肝疾患の予防または改善用組成物 | |
KR100544711B1 (ko) | 항암효능을 갖는 비타민 k3 및 퀘르세틴을 포함하는 식품 | |
EP4248957A1 (en) | Method for treating non-alcoholic steatohepatitis through co-administration of curcumin derivative and tgf-? receptor inhibitor | |
KR102233672B1 (ko) | 엉겅퀴 및 돼지감자를 포함하는 혼합물을 함유하는 당뇨의 예방, 치료 또는 개선용 조성물 | |
KR102130107B1 (ko) | 아라비노자일란 함유 미강 추출물을 포함하는 신경병증 또는 청각손상 예방 또는 치료용 조성물 | |
JP2002080380A (ja) | 骨形成促進剤 | |
KR101490800B1 (ko) | 붉은덕다리버섯의 물 추출물을 포함하는 고지혈증 치료 또는 예방용 조성물 | |
KR20230000907A (ko) | 커큐민 유도체와 TGF-β 수용체 억제제의 병용투여를 통한 비알코올성 지방간염 치료 방법 | |
KR20050107385A (ko) | 허수테논을 함유하는 건강 증진용 식품 | |
JP2002080379A (ja) | 生殖機能増強剤 | |
KR20180129286A (ko) | 아로니아 추출물을 유효성분으로 포함하는 인지능 개선 식품 조성물 건강식품 | |
KR20230053817A (ko) | 흑오미자 추출물을 유효성분으로 함유하는 골 질환의 예방, 개선 또는 치료용 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170609 Termination date: 20200815 |