CN105456298A - Anti-senile dementia activity of bryostatins and application thereof - Google Patents
Anti-senile dementia activity of bryostatins and application thereof Download PDFInfo
- Publication number
- CN105456298A CN105456298A CN201510863912.6A CN201510863912A CN105456298A CN 105456298 A CN105456298 A CN 105456298A CN 201510863912 A CN201510863912 A CN 201510863912A CN 105456298 A CN105456298 A CN 105456298A
- Authority
- CN
- China
- Prior art keywords
- active component
- total lactones
- tongue worm
- obtains
- careless tongue
- 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.)
- Pending
Links
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 36
- 206010039966 Senile dementia Diseases 0.000 title claims abstract description 36
- 229960005520 bryostatin Drugs 0.000 title abstract description 22
- 230000000694 effects Effects 0.000 title abstract description 17
- MJQUEDHRCUIRLF-YCVQJEHTSA-N bryostatins Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)C([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-YCVQJEHTSA-N 0.000 title abstract 6
- 239000003814 drug Substances 0.000 claims abstract description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 101
- 241001541122 Linguatula serrata Species 0.000 claims description 58
- 150000002596 lactones Chemical class 0.000 claims description 56
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 20
- 238000000605 extraction Methods 0.000 claims description 15
- 230000036541 health Effects 0.000 claims description 15
- 241000700675 Bugula neritina Species 0.000 claims description 14
- 239000000284 extract Substances 0.000 claims description 12
- 230000002265 prevention Effects 0.000 claims description 11
- 238000001641 gel filtration chromatography Methods 0.000 claims description 10
- OUVYQBNLDHLZNW-XLMAGYEKSA-N bryostatin 4 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(=O)CC(C)C)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C/C(=O)OC)C[C@H]\2O1 OUVYQBNLDHLZNW-XLMAGYEKSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 230000006837 decompression Effects 0.000 claims description 5
- 238000010828 elution Methods 0.000 claims description 5
- 239000000469 ethanolic extract Substances 0.000 claims description 5
- 239000002035 hexane extract Substances 0.000 claims description 5
- 238000004064 recycling Methods 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 238000007796 conventional method Methods 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000007919 dispersible tablet Substances 0.000 claims description 2
- 239000006196 drop Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000007901 soft capsule Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 229960004373 acetylcholine Drugs 0.000 abstract description 19
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 abstract description 18
- 241000699670 Mus sp. Species 0.000 abstract description 15
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 abstract description 14
- 210000002966 serum Anatomy 0.000 abstract description 10
- 210000004556 brain Anatomy 0.000 abstract description 9
- 229960003180 glutathione Drugs 0.000 abstract description 9
- 108010058699 Choline O-acetyltransferase Proteins 0.000 abstract description 8
- 102100023460 Choline O-acetyltransferase Human genes 0.000 abstract description 8
- 238000002474 experimental method Methods 0.000 abstract description 7
- 231100000419 toxicity Toxicity 0.000 abstract description 7
- 230000001988 toxicity Effects 0.000 abstract description 7
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- 102000006587 Glutathione peroxidase Human genes 0.000 abstract description 4
- 108700016172 Glutathione peroxidases Proteins 0.000 abstract description 4
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 4
- 108010024636 Glutathione Proteins 0.000 abstract description 3
- 230000009182 swimming Effects 0.000 abstract description 3
- 108090000371 Esterases Proteins 0.000 abstract description 2
- 238000011161 development Methods 0.000 abstract description 2
- 230000006872 improvement Effects 0.000 abstract description 2
- 229940118019 malondialdehyde Drugs 0.000 abstract 2
- 230000009278 visceral effect Effects 0.000 abstract 1
- MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 description 19
- 238000012360 testing method Methods 0.000 description 18
- MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 description 16
- 238000011160 research Methods 0.000 description 15
- 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 12
- 102000012440 Acetylcholinesterase Human genes 0.000 description 10
- 108010022752 Acetylcholinesterase Proteins 0.000 description 10
- 229940022698 acetylcholinesterase Drugs 0.000 description 10
- 102000019197 Superoxide Dismutase Human genes 0.000 description 8
- 108010012715 Superoxide dismutase Proteins 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 235000003969 glutathione Nutrition 0.000 description 7
- 108090000992 Transferases Proteins 0.000 description 6
- 102000004357 Transferases Human genes 0.000 description 6
- 229930003427 Vitamin E Natural products 0.000 description 6
- 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 6
- 235000019165 vitamin E Nutrition 0.000 description 6
- 229940046009 vitamin E Drugs 0.000 description 6
- 239000011709 vitamin E Substances 0.000 description 6
- 230000001093 anti-cancer Effects 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 229960005539 bryostatin 1 Drugs 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 102000013918 Apolipoproteins E Human genes 0.000 description 2
- 108010025628 Apolipoproteins E Proteins 0.000 description 2
- 241000700670 Bryozoa Species 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 230000003005 anti-senility effect Effects 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000002932 cholinergic neuron Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 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 2
- 238000001647 drug administration Methods 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000003120 macrolide antibiotic agent Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- 108700016155 Acyl transferases Proteins 0.000 description 1
- 102000057234 Acyl transferases Human genes 0.000 description 1
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 241001450685 Corallium japonicum Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241001428166 Eucheuma Species 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- ZRJBHWIHUMBLCN-SEQYCRGISA-N Huperzine A Natural products N1C(=O)C=CC2=C1C[C@H]1/C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-SEQYCRGISA-N 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000012347 Morris Water Maze Methods 0.000 description 1
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000002329 esterase inhibitor Substances 0.000 description 1
- 238000009313 farming Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 229930184727 ginkgolide Natural products 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- ZRJBHWIHUMBLCN-YQEJDHNASA-N huperzine A Chemical compound N1C(=O)C=CC2=C1C[C@H]1\C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-YQEJDHNASA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- -1 mda content Proteins 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 210000001682 neurofibril Anatomy 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002547 new drug Substances 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
- 102000004169 proteins and genes Human genes 0.000 description 1
- ZRJBHWIHUMBLCN-BMIGLBTASA-N rac-huperzine A Natural products N1C(=O)C=CC2=C1C[C@@H]1C(=CC)[C@@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-BMIGLBTASA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960004136 rivastigmine 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
- 229960003946 selegiline Drugs 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 229960001685 tacrine Drugs 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- 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
Abstract
The invention relates to the technical field of medicine, in particular to the anti-senile dementia activity of bryostatins and application thereof. According to the bryostatins (BRYS), mouse water maze experiments are conducted, the swimming time can be significantly shortened, obvious improvement effects on acetylcholine esterase (AChE) and acetylcholine (Ach) in mouse brains are achieved, the contents of choline acetyl transferase (ChAT) and malondialdehyde (MDA) are both obviously increased, the effect is significant, and differences are statistically significant. The SOD activity in serum can be significantly increased, P is smaller than 0.01, and the levels of serum reduced glutathione (GSH) and serum glutathione peroxidase (GSH-PX) are increased. In addition, the bryostatins has no obvious influence on the quality of mice and visceral indexes, and it is shown that the toxicity is low. It is shown through experimental results that the bryostatins has significant anti-senile dementia activity and lower toxicity and can be applied to development of drugs for resisting senile dementia.
Description
Technical field
The present invention relates to medical art, be specifically related to the anti-senile dementia activity of careless tongue worm total lactones and the application in field of medicaments thereof.
Background technology
Ocean bryozoan is commonly called as bryozoan, extra large mat, false Corallium Japonicum Kishinouye and tongue worm, and belonging to Eucoelomata, is one of important composition of marine benthos.Its kind is a lot, and nearly kind more than 4000, modal is bugula neritina.Bugula neritina BugulaneritinaLinnaeus is widely distributed in waters, the world, and the polyhaline territory in the Xisha Islands of China coast from the Bohai Sea to the South Sea has.This colony is bronzing or puce, and in thick grass shape, high 40 ~ 150mm, has often propped up worm two row, arranged alternately.Its colony is often attached on the underwater facilities such as Thallus Laminariae (Thallus Eckloniae), Eucheuma gelatinosum, shellfish and hull bottom, harbour, navigation mark, and affecting sea farming and national defence, sea traffic, is one of main fouling organism in ocean.Until nineteen sixty-eight, State of Arizona, US founds university Pettit research group in oceanic invertebrate and vertebrate extensive research, the Late Cambrian active anticancer of bugula neritina.Through the effort of more than ten years, nineteen eighty-two Pettit research group is successfully separated and obtains the monomer bryostatin1 that first has active anticancer from the bugula neritina being collected in marine site, California, and its structure is determined with X diffraction approach, be macrolides compound.From then on, this group is devoted to the research in bugula neritina with active anticancer macrolide composition always.So far, therefrom obtain 20 activated monomers, i.e. bryostatin1 ~ 20 (LinHW, YiYH, LiWL, YaoXS, WuHM.ChineseJ.MarineDrugs1998,65,1; PettitGR.FortschrittederChemieOrganischerNaturstoffe, 1991,57,153).Bryostatin1 and bryostatin4, through the bioassay of national cancer institute (NCI), drops into clinical trial.This compounds has low, the active strong feature of toxicity.It acts on the mechanism of action of the novelty of Protein kinase C (PKC), excites the research extensively and profoundly of researcher to its mechanism of action.The natural resources limited in view of careless tongue worm and the pettiness content of bryostatin, the extensive investigations that people carry out its natural resources.
Senile dementia (being mainly Alzheimer) is the lethal neurodegenerative diseases of a kind of Progressive symmetric erythrokeratodermia development, clinical manifestation is cognitive and memory function constantly worsens, activity of daily living Progressive symmetric erythrokeratodermia goes down, and has various neuropsychic symptom and behavior disorder.This disease can occur at any age, but usually occurred between 60-70.When being diagnosed as this disease, approximately can also survive 3.3 years.Health status shows, and the prevalence of 60 years old crowd is 1%, and the age often increases by 5 years old, and prevalence increases by 2 times.Current China is just accelerating to enter aging society, and according to relevant expert's prediction, will reach 400,000,000 to the year two thousand twenty China more than 60 years old population, senile dementia patient will have more than 10,000,000 people.Latest report, patients of senile dementia just existing 120,000 people that Shanghai is current.
Senile dementia is the not bright constitutional degeneration brain degenerative disease of one group of cause of disease, and a lot of disease is in the geratic period, and onset of hiding, the course of disease is slow and irreversible, clinically based on intelligence damage.Pathological change is mainly cortex diffuse atrophy, and ditch returns broadening, and the ventricles of the brain expand, and neuron reduces in a large number, and visible senile plaque (SP), the pathological changes such as neurofibril knot (NFT), choline acetylase and acetyl choline content significantly reduce.Senile dementia pathogenesis etiology is also not fully aware of at present, and has multiple hypotype, and the organ that pathological change occurs also may have other organs except brain.The pathogenesis of generally acknowledging at present mainly contains two kinds: 1. because the exception of amyloid precursor protein causes protein ingredient to spill cell membrane, cause neurofibrillary tangle and cell death, gene is positioned at No. 21 chromosomes.AD patient's brain acetylcholine obviously lacks, and acetylcholinesterase and choline one acyltransferase activity reduce, particularly Hippocampus and cortex of temporal lobe position.2. relevant with the gene of apo E (APO-E4).
Because the current definite cause of disease of senile dementia is not yet thrown a flood of light on, Therapeutic Method mainly by drug effect in different neurotransmitter systems, strengthen the high-grade movable of central nervous system, the various symptoms occurred in the process that palliates a disease, delay dull-witted further developing.Treatment conventional clinically improves acetyl choline content in patient body mainly through acetylcholine esterase inhibition, improves the clinical symptoms of senile dementia.The medicine of current Clinical practice mostly is acetylcholinesteraseinhibitors inhibitors (as tacrine, donepezil, Rivastigmine, galantamine, huperzine A), nmda receptor antagonist (memantine) and antioxidant (selegiline, vitamin E, melatonin, Semen Ginkgo extrac) etc. are more with the Drug therapy of cognitive dysfunction, but clinical efficacy is definite all not, oral absorption is poor, not easily or toxic and side effects strong through blood brain barrier, specificity the shortcoming such as greatly, particularly to cure the symptoms, not the disease.The new drug researching and developing new and effective anti-senile dementia is problem in the urgent need to address in current medicines and health protection.But also have larger gap in this research field with external similar research at present.Find from natural product and find that the chemical composition of anti-senile dementia is the new focus of in researches on natural drugs one and developing direction.Particularly marine natural products, owing to having special chemical constitution and physiologically active, therefrom finds that the chemical composition of anti-senile dementia will have more wide prospect.
About the anti-senile dementia of careless tongue worm total lactones is active, there is not yet report both at home and abroad.
Summary of the invention
The object of the present invention is to provide careless tongue worm total lactones and preparation method thereof; Another object of the present invention is to the new medical usage that careless tongue worm total lactones is provided.
A first aspect of the present invention, provides a kind of careless tongue worm total lactones, and described careless tongue worm total lactones take bugula neritina as raw material, through conventional method extraction purification, obtains careless tongue worm total lactones.
Careless tongue worm total lactones of the present invention, through high performance liquid chroma-tography analysis, mainly containing BRYOSTATIN-5,10, more than the 10 kind of Ginkgolide Components such as 18 and 4, wherein the highest with the content of BRYOSTATIN-4.Bryostatin4 accounts for careless tongue worm total lactones more than 60% (mass percent).
Preferably, bugula neritina collection is from south China marine site.
A second aspect of the present invention, provides a kind of preparation method of careless tongue worm total lactones.
A preparation method for careless tongue worm total lactones, is characterized in that, the preparation method of described careless tongue worm total lactones is as follows:
The bugula neritina BugulaneritinaLinnaeus of fresh collection, with 95% ethanol room temperature lixiviate, by ethanol extract, decompression recycling ethanol, obtains extractum;
Extractum 90% methanol suspension disperses, and with n-hexane extraction, discards N-hexane extract; Aqueous methanol layer adds water into 80% methanol aqueous solution again, uses CCl
4extraction, obtains CCl
4extract;
CCl
4extract obtains active component through 200 ~ 300 order silica gel column chromatographies; Again through SephadexLH-20 gel filtration chromatography, with CH
2cl
2﹕ MeOH (1 ﹕ 1) eluting, flow velocity 60mL/h, obtains active component A and active component B;
Carry out twice gel filtration chromatography respectively to active component A and active component B, first time is with Hexane ﹕ CH
2cl
2﹕ MeOH (4:5:1) eluting, second time is with Hexane ﹕ CH
2cl
2﹕ MeOH (10 ﹕ 10 ﹕ 1) eluting, obtains active component C and active component D respectively;
Active component C and active component D carries out ODS rapid column chromatography, with 50%, 80%MeOH gradient elution, obtains careless tongue worm total lactones.
In a preferred embodiment of the invention, the preparation method of described careless tongue worm total lactones, specific as follows:
The bugula neritina BugulaneritinaLinnaeus raw material of fresh collection, with 95% ethanol room temperature lixiviate one week, extract 4 times altogether, merge ethanol extract, decompression recycling ethanol, obtains extractum.Extractum 90% methanol suspension disperses, and with n-hexane extraction 5 times, obtains N-hexane extract, through Anticancer Activity in vitro screening non-activity, discards.Aqueous methanol layer adds water and makes into 80% methanol aqueous solution, uses CCl
4extract 5 times, obtain CCl
4extract is active site.This active site obtains active component through Flash silica column chromatography (200 ~ 300 order).Again through SephadexLH-20 gel filtration chromatography, with CH
2cl
2﹕ MeOH (1 ﹕ 1) eluting, flow velocity 60mL/h, obtains two active component A and B.Respectively twice gel filtration chromatography is carried out, successively with Hexane-CH to these two active components
2cl
2-MeOH (4:5:1) and Hexane ﹕ CH
2cl
2﹕ MeOH (10 ﹕ 10 ﹕ 1) eluting, obtains higher, active two the stronger component C and D of purity respectively.C, D two component still containing more marennin, therefore both to be merged, carry out ODS rapid column chromatography, with 50%, 80%MeOH gradient elution, obtain light yellow total bryostatin (BRYS).
95% described ethanol consumption is 20-30 times (weight ratio) of raw material.
Described n-hexane extraction 5 times, each consumption 4-5L.
Described CCl
4extract 5 times, each consumption 1-2L.
A third aspect of the present invention, provides the new medical usage of above-mentioned careless tongue worm total lactones.
The invention provides the application of careless tongue worm total lactones in preparation prevention or treatment medicine for senile dementia or health product.
In the application of careless tongue worm total lactones of the present invention in preparation prevention or treatment medicine for senile dementia or health product, in described medicine or health product: careless tongue worm total lactones as sole active composition, or comprises the compositions of careless tongue worm total lactones.
In described medicine or health product, the content of careless tongue worm total lactones is 0.1-99wt%, and preferred content is 0.5-90wt%.
In described medicine, careless tongue worm total lactones, the pharmaceutical composition comprising careless tongue worm total lactones can make pharmaceutical preparation with the conventional pharmaceutical adjuvants on pharmaceutics.
Described pharmaceutical preparation can be tablet, granule, dispersible tablet, capsule, soft capsule, drop pill, injection, injectable powder, or aerosol etc.
The present invention studies discovery, and careless tongue worm total lactones possesses anti-senile dementia biological activity:
Male ICR mouse is divided into 9 groups at random, often organizes mice 6.If matched group, BRYS medicine is established: 0.0025mg/kg, 0.005mg/kg, 0.01mg/kg group, Antisenility Experiment positive drug (vitamin E).BRYS and vitamin E drug administration by injection, totally 60 days.After last administration 1h, whole mice is cooked water maze laboratory, continues one week, and record mice finds the time of platform.In Mice water maze experiment, careless tongue worm total lactones (BRYS) is compared with model group, and middle concentration group and high concentration group significantly can shorten swimming time.After one week, according to test kit description processing sample, detect brain homogenate Acetylcholinesterasein, acetylcholine transferase content and serum activity of SOD, mda content, glutathione peroxidase activity, acetyl choline content, glutathione content.Experimental data adopts SPSS13.0 software processes, and data carry out t inspection.Experimental result shows, and careless tongue worm total lactones has obvious anti-senile dementia active.In addition, careless tongue worm total lactones all affects without obvious weight and organ index, shows that toxicity is lower.
Above experimental result shows, careless tongue worm total lactones has the active and lower toxicity of significant anti-senile dementia, can be used for the medicine developing anti-senile dementia.
Due to, in careless tongue worm total lactones of the present invention, the highest with the content of BRYOSTATIN-4, Bryostatin4 accounts for careless tongue worm total lactones more than 60%.Therefore, present invention provides the application of Bryostatin4 in preparation prevention or treatment medicine for senile dementia or health product.
The present invention has searched out the medicine of anti-senile dementia safely and effectively.
Detailed description of the invention
Below in conjunction with detailed description of the invention, explain the present invention further.The experimental technique used in following embodiment if no special instructions, is conventional method.Material used in following embodiment and reagent etc., if no special instructions, all can obtain from commercial channels.These embodiments are only not used in for illustration of the present invention and limit the scope of the invention.
The extraction purification of embodiment 1. careless tongue worm total lactones
The bugula neritina BugulaneritinaLinnaeus raw material (10kg, dry weight) of fresh collection, with 95% ethanol room temperature lixiviate one week, extract 4 times (300L/ time, 4 times) altogether, merge ethanol extract, decompression recycling ethanol, obtains extractum 320g.Extractum 90% methanol suspension disperses, and with n-hexane extraction 5 each 5L, obtains N-hexane extract 56g, through Anticancer Activity in vitro screening non-activity.Aqueous methanol layer adds water and makes into 80% methanol aqueous solution, uses CCl
4extraction (1L/ time, 5 times), obtains CCl
4extract 9g (IC50=7 μ g/mL, P388) is active site.This active site obtains active component 2BH-10 (0.41g, IC50=2.4g/mL, P388) through Flash silica column chromatography (200 ~ 300 order).2BH-10 through SephadexLH-20 gel filtration chromatography, with CH
2cl
2﹕ MeOH (1 ﹕ 1) eluting, flow velocity 60mL/h, obtains two active component A (0.17g, IC50=0.3 μ g/mL, P388) and B (0.11g, IC50=0.8g/mL, P388).Respectively twice gel filtration chromatography is carried out, successively with Hexane-CH to these two active components
2cl
2-MeOH (4:5:1) and Hexane ﹕ CH
2cl
2﹕ MeOH (10 ﹕ 10 ﹕ 1) eluting, obtains higher, active two the stronger component C (0.07g, IC50=0.1g/ml, P388) of purity and D (0.05g, IC50=810-2g/mL, P388) respectively.C, D two component still containing more marennin, therefore both to be merged, carry out ODS rapid column chromatography, with 50%, 80%MeOH gradient elution, obtain light yellow total bryostatin (BRYS) 0.01 gram.
Embodiment 2. bryostatin anti-senile dementia biological activity test
1 experiment material
1.1 laboratory animals: ICR mice, male, 6-8 week age, 18-22g, Dalian Medical Univ, 1.2 reagent and medicine: acetylcholinesterase (AChE) test kit (Bioengineering Research Institute is built up in Nanjing), acetylcholine transferase (ChAT) test kit (Bioengineering Research Institute is built up in Nanjing), glutathion peroxidase testing cassete (Bioengineering Research Institute is built up in Nanjing), trace reduced glutathion test kit (Bioengineering Research Institute is built up in Nanjing), acetylcholine test kit (Bioengineering Research Institute is built up in Nanjing), SOD test kit (Bioengineering Research Institute is built up in Nanjing), malonaldehyde testing cassete (Bioengineering Research Institute is built up in Nanjing), vitamin E (Dalian Tianyu Orson Pharmaceutical Co., Ltd.), test medicine: the careless tongue worm total lactones (BRYS) that embodiment 1 obtains.
1.3 instruments: microplate reader, centrifuge.
2 experimental techniques
2.1 experimental programs: mice is divided into 9 groups at random, often organize mice 6.If matched group, careless tongue worm total lactones is established: 0.0025mg/kg, 0.005mg/kg, 0.01mg/kg group, Antisenility Experiment positive drug group (vitamin E, VE).BRYS and vitamin E drug administration by injection, totally 60 days.After last administration 1h, whole mice is cooked water maze laboratory, continues one week, and record mice finds the time of platform.Water maze laboratory method is see document: Wang Weigang etc., the application of Morris water maze laboratory in mouse phenotype is analyzed, Chinese cytobiology journal, 2011, (1): 8-14.
After one week, according to each test kit description processing sample, detect indices:
Acetylcholinesterase (AChE) test kit, detects brain homogenate Acetylcholinesterasein;
Acetylcholine transferase (ChAT) test kit, detects acetylcholine transferase content;
Glutathion peroxidase testing cassete, detects glutathione peroxidase activity;
Trace reduced glutathion test kit, detects glutathione content;
Acetylcholine test kit, detects acetyl choline content;
SOD test kit, detects serum activity of SOD;
Malonaldehyde testing cassete, detects mda content.
2.2 experimental data inspections: adopt SPSS13.0 software processes, data carry out t inspection.
2.3 experimental results: in Table 1-4.
Table 1 Mice water maze X ± SD
* P < 0.05, * * P < 0.01 is compared with model group
The vigor of AChE in table 2 mice 10% brain homogenate, the content of ChAT, MDA content X ± SD
* P < 0.05, * * P < 0.01 is compared with model group
The vigor of SOD in table 3 mice serum, MDA, Ach, GSH content, GSH-PX vigor X ± SD
Table 4 Mice Body quality, brain, liver, spleen, thymus, testis index (X ± SD)
2.4 conclusion
Mice water maze is tested, and careless tongue worm total lactones (BRYS) is compared with model group, and middle concentration group and high concentration group significantly can shorten swimming time; Cholinergic neuron plays an important role in learning and memory process, acetylcholine (Ach) is a kind of important central neurotransmitter that cholinergic neuron end slightly discharges, and acetylcholine esterase (AChE) and acetylcholine transferase (ChAT) maintain the stable of Ach level jointly.(AChE) be the hydrolytic enzyme of acetylcholine.AChE level can reflect the change of Ach indirectly.BRYS is compared with model group, and high concentration group improves significantly (P<0.05) to AChE and Ach.Cerebral tissue acetylcholine transferase (ChAT), BRYS is compared with model group, and high concentration group has a better role (P<0.05).BRYS respectively organizes cerebral tissue malonaldehyde (MDA) content and all has clear improvement, and its middle and high concentration group effect is remarkable, and difference has statistical significance (P<0.05).Serum superoxide dismutases (SOD) has balanced crucial regulating and controlling effect to body oxidative and anti-oxidative, can remove ultra-oxygen anion free radical, reduces lipid peroxidation, maintains biofilm structure and function thereof, Cell protection.BRYS significantly can increase SOD vigor (P<0.01) in serum, increasing serum reduced glutathion (GSH) and Serum glutathione peroxidase (GSH-PX) level.In addition, careless tongue worm total lactones all affects without obvious weight and organ index, shows that toxicity is lower.
Above experimental result shows, careless tongue worm total lactones has the active and lower toxicity of significant anti-senile dementia, can be used for the medicine developing anti-senile dementia.
Below the preferred embodiment of the invention is illustrated, but the invention is not limited to described embodiment, those of ordinary skill in the art also can make all equivalent modification or replacement under the prerequisite without prejudice to the invention spirit, and these equivalent modification or replacement are all included in the application's claim limited range.
Claims (10)
1. the application of careless tongue worm total lactones in preparation prevention or treatment medicine for senile dementia or health product.
2. the application of careless tongue worm total lactones according to claim 1 in preparation prevention or treatment medicine for senile dementia or health product, it is characterized in that, described careless tongue worm total lactones take bugula neritina as raw material, through conventional method extraction purification, obtains careless tongue worm total lactones.
3. the application of careless tongue worm total lactones according to claim 1 in preparation prevention or treatment medicine for senile dementia or health product, it is characterized in that, in described careless tongue worm total lactones, Bryostatin4 accounts for more than 60%.
4. the application of careless tongue worm total lactones according to claim 1 in preparation prevention or treatment medicine for senile dementia or health product, it is characterized in that, the preparation method of described careless tongue worm total lactones is as follows:
The bugula neritina BugulaneritinaLinnaeus of fresh collection, with 95% ethanol room temperature lixiviate, by ethanol extract, decompression recycling ethanol, obtains extractum;
Extractum 90% methanol suspension disperses, and with n-hexane extraction, discards N-hexane extract; Aqueous methanol layer adds water into 80% methanol aqueous solution again, uses CCl
4extraction, obtains CCl
4extract;
CCl
4extract obtains active component through 200 ~ 300 order silica gel column chromatographies; Again through SephadexLH-20 gel filtration chromatography, with CH
2cl
2﹕ MeOH is 1 ﹕ 1 eluting, and flow velocity 60mL/h, obtains active component A and active component B;
Carry out twice gel filtration chromatography respectively to active component A and active component B, first time is with Hexane ﹕ CH
2cl
2﹕ MeOH is 4:5:1 eluting, and second time is with Hexane ﹕ CH
2cl
2﹕ MeOH is 10 ﹕ 10 ﹕ 1 eluting, obtains active component C and active component D respectively;
Active component C and active component D carries out ODS rapid column chromatography, with 50%, 80%MeOH gradient elution, obtains careless tongue worm total lactones.
5. according to the application of the arbitrary described careless tongue worm total lactones of Claims 1-4 in preparation prevention or treatment medicine for senile dementia or health product, it is characterized in that, in described medicine or health product, careless tongue worm total lactones as sole active composition, or comprises the compositions of careless tongue worm total lactones.
6. the application of careless tongue worm total lactones according to claim 5 in preparation prevention or treatment medicine for senile dementia or health product, it is characterized in that, in described medicine, careless tongue worm total lactones, the pharmaceutical composition comprising careless tongue worm total lactones can make pharmaceutical preparation with the conventional pharmaceutical adjuvants on pharmaceutics.
7. the application of careless tongue worm total lactones according to claim 6 in preparation prevention or treatment medicine for senile dementia or health product, it is characterized in that, described pharmaceutical preparation is tablet, granule, dispersible tablet, capsule, soft capsule, drop pill, injection, injectable powder, or aerosol.
8.Bryostatin4 the application in preparation prevention or treatment medicine for senile dementia or health product.
9. a preparation method for careless tongue worm total lactones, is characterized in that, the preparation method of described careless tongue worm total lactones is as follows:
The bugula neritina BugulaneritinaLinnaeus of fresh collection, with 95% ethanol room temperature lixiviate, by ethanol extract, decompression recycling ethanol, obtains extractum;
Extractum 90% methanol suspension disperses, and with n-hexane extraction, discards N-hexane extract; Aqueous methanol layer adds water into 80% methanol aqueous solution again, uses CCl
4extraction, obtains CCl
4extract;
CCl
4extract obtains active component through 200 ~ 300 order silica gel column chromatographies; Again through SephadexLH-20 gel filtration chromatography, with CH
2cl
2﹕ MeOH is 1 ﹕ 1 eluting, and flow velocity 60mL/h, obtains active component A and active component B;
Carry out twice gel filtration chromatography respectively to active component A and active component B, first time is with Hexane ﹕ CH
2cl
2﹕ MeOH is 4:5:1 eluting, and second time is with Hexane ﹕ CH
2cl
2﹕ MeOH is 10 ﹕ 10 ﹕ 1 eluting, obtains active component C and active component D respectively;
Active component C and active component D carries out ODS rapid column chromatography, with 50%, 80%MeOH gradient elution, obtains careless tongue worm total lactones.
10. the preparation method of a kind of careless tongue worm total lactones according to claim 9, is characterized in that, with 95% ethanol room temperature lixiviate, the consumption of 95% ethanol is 20-30 times of the bugula neritina raw material of fresh collection; Described n-hexane extraction totally 5 times, the consumption of each normal hexane is 4-5L; Described CCl
4extraction totally 5 times, each CCl
4consumption be 1-2L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510863912.6A CN105456298A (en) | 2015-12-01 | 2015-12-01 | Anti-senile dementia activity of bryostatins and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510863912.6A CN105456298A (en) | 2015-12-01 | 2015-12-01 | Anti-senile dementia activity of bryostatins and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105456298A true CN105456298A (en) | 2016-04-06 |
Family
ID=55594762
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510863912.6A Pending CN105456298A (en) | 2015-12-01 | 2015-12-01 | Anti-senile dementia activity of bryostatins and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105456298A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109071559A (en) * | 2016-05-04 | 2018-12-21 | 亲神经剂生物科学有限公司 | For treating the method and composition of rett's syndrome |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1178793A (en) * | 1997-10-31 | 1998-04-15 | 中国人民解放军第二军医大学药学院 | Bryostatin as anti-cancer active compound |
| CN1224721A (en) * | 1998-11-11 | 1999-08-04 | 中国人民解放军第二军医大学 | Extraction and separation method of total bryostatin with superstrong anticancer activity |
| CN1678304A (en) * | 2002-07-02 | 2005-10-05 | 布朗歇特洛克菲勒神经科学研究所 | PKC activation as a means for enhancing aAPP-a secretion and improving cognition using bryostatin type compounds |
| CN1934117A (en) * | 2004-03-02 | 2007-03-21 | 惠氏公司 | Macrolides and methods for producing same |
-
2015
- 2015-12-01 CN CN201510863912.6A patent/CN105456298A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1178793A (en) * | 1997-10-31 | 1998-04-15 | 中国人民解放军第二军医大学药学院 | Bryostatin as anti-cancer active compound |
| CN1224721A (en) * | 1998-11-11 | 1999-08-04 | 中国人民解放军第二军医大学 | Extraction and separation method of total bryostatin with superstrong anticancer activity |
| CN1678304A (en) * | 2002-07-02 | 2005-10-05 | 布朗歇特洛克菲勒神经科学研究所 | PKC activation as a means for enhancing aAPP-a secretion and improving cognition using bryostatin type compounds |
| CN1934117A (en) * | 2004-03-02 | 2007-03-21 | 惠氏公司 | Macrolides and methods for producing same |
Non-Patent Citations (1)
| Title |
|---|
| 林厚文等: "中国南海总合草苔虫抗癌活性成分研究II 总草苔虫内酯的超强抗癌活性", 《中国海洋药物》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109071559A (en) * | 2016-05-04 | 2018-12-21 | 亲神经剂生物科学有限公司 | For treating the method and composition of rett's syndrome |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101342259B (en) | Method for extracting alkaloid valid parts from hooked uncaria leaf, with hook stem branch or full grass and uses thereof | |
| KR100896700B1 (en) | A.tuberosum Rottl. extract having an activity of activating choline acetyltransferase in brain nerve cells | |
| US20130189382A1 (en) | Use of fucoxanthin in the preparation of product for improving memory and having neuroprotective effect associated with neurodegenerative disorder | |
| Li et al. | Benzoate fraction from Gentiana rigescens Franch alleviates scopolamine-induced impaired memory in mice model in vivo | |
| CN108472325B (en) | Composition for improving memory comprising petasites japonicus leaf extract | |
| JP2016502983A (en) | Algal extracts containing sulfated and non-sulfated polyanionic polysaccharides and uses thereof | |
| JP2008156240A (en) | Cerebral function-improving agent | |
| JP6781881B2 (en) | Ephedrine alkaloid-removing ephedra extract and its manufacturing method and uses | |
| KR101829583B1 (en) | Pharmaceutical composition having anti-depressant activity and preparation method using Vaccinium bracteatum Thunb. of the same. | |
| CN102935100A (en) | Preparation method and applications of queen lagerstroemia folium apocyni veneti general flavones | |
| CN105456298A (en) | Anti-senile dementia activity of bryostatins and application thereof | |
| CN111437323A (en) | Application of vine tea extract in medicine for preventing and treating Alzheimer disease | |
| CN107693530A (en) | Aurantiamarin and/or aurantiin are preparing the application in improving cognition dysfunction medicine | |
| CN1316976C (en) | Use of kaempferol-3-O-glubulariacitrin in preparing medicine for senile dementia | |
| CN102895438B (en) | Application of rhizoma acori graminei extract in preparing drug for treating Alzheimer | |
| CN106727928A (en) | Prunella vulgaris extract and preparation method and application | |
| KR101055920B1 (en) | Alzheimer's disease prevention or treatment composition comprising 8-methoxysorene separated from the tanza and method for separating the compound | |
| CN112940001A (en) | Phthalide isoquinoline alkaloid and preparation method and application thereof | |
| CN104130232B (en) | The method of purification of a kind of EGCG and the EGCG of acquisition and pharmaceutical composition | |
| KR20160136855A (en) | Composition for ameliorating cognitive functions comprising extacts from processed Polygoni Multiflori Radix | |
| CN115837040B (en) | Application of ligusticum chuanxiong hort extract in preparation of medicine for preventing and treating cognitive dysfunction | |
| CN112830947B (en) | Stilbene compounds isolated from Rheum lhasaense and their use in treating nervous system diseases | |
| CN113694055B (en) | Application of agalloch eaglewood tetrol in preparing medicine for treating vascular dementia | |
| JP6670531B1 (en) | Nerve cell death inhibitor and food composition for suppressing nerve cell death | |
| CN102178664B (en) | Application of schizandrol A, schizandrin and schizandrol extract to prevention and treatment of senile dementia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160406 |
|
| RJ01 | Rejection of invention patent application after publication |