CN117045713A - Chinese medicinal preparation for inhibiting beta secretase activity and preventing and treating senile dementia and its production method - Google Patents
Chinese medicinal preparation for inhibiting beta secretase activity and preventing and treating senile dementia and its production method Download PDFInfo
- Publication number
- CN117045713A CN117045713A CN202311140892.0A CN202311140892A CN117045713A CN 117045713 A CN117045713 A CN 117045713A CN 202311140892 A CN202311140892 A CN 202311140892A CN 117045713 A CN117045713 A CN 117045713A
- Authority
- CN
- China
- Prior art keywords
- parts
- preventing
- senile dementia
- beta
- traditional chinese
- 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
- 230000000694 effects Effects 0.000 title claims abstract description 50
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 title claims abstract description 37
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- 206010039966 Senile dementia Diseases 0.000 title claims abstract description 18
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 48
- 210000004556 brain Anatomy 0.000 claims abstract description 36
- 240000000249 Morus alba Species 0.000 claims abstract description 13
- 235000008708 Morus alba Nutrition 0.000 claims abstract description 13
- 244000197580 Poria cocos Species 0.000 claims abstract description 12
- 235000008599 Poria cocos Nutrition 0.000 claims abstract description 12
- 240000008866 Ziziphus nummularia Species 0.000 claims abstract description 11
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims abstract description 10
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims abstract description 10
- 230000001965 increasing effect Effects 0.000 claims abstract description 8
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 claims abstract description 5
- 239000002243 precursor Substances 0.000 claims abstract description 5
- 241000213006 Angelica dahurica Species 0.000 claims abstract 5
- 238000000034 method Methods 0.000 claims description 17
- 239000007788 liquid Substances 0.000 claims description 15
- 239000008187 granular material Substances 0.000 claims description 10
- 239000003826 tablet Substances 0.000 claims description 7
- 239000002775 capsule Substances 0.000 claims description 6
- 230000006933 amyloid-beta aggregation Effects 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 2
- 238000002474 experimental method Methods 0.000 abstract description 20
- 229940079593 drug Drugs 0.000 abstract description 12
- 210000004369 blood Anatomy 0.000 abstract description 11
- 239000008280 blood Substances 0.000 abstract description 11
- 238000001556 precipitation Methods 0.000 abstract description 7
- 230000002829 reductive effect Effects 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000002936 tranquilizing effect Effects 0.000 abstract description 6
- 239000004480 active ingredient Substances 0.000 abstract description 5
- 230000003930 cognitive ability Effects 0.000 abstract description 4
- 230000002708 enhancing effect Effects 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract description 4
- 208000006820 Arthralgia Diseases 0.000 abstract description 3
- 230000007087 memory ability Effects 0.000 abstract description 3
- 230000007507 senile plaque formation Effects 0.000 abstract description 3
- 208000022288 senile plaque formation Diseases 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract description 2
- 230000003213 activating effect Effects 0.000 abstract 1
- 238000011282 treatment Methods 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 238000000540 analysis of variance Methods 0.000 description 11
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 10
- 229910052782 aluminium Inorganic materials 0.000 description 10
- 238000011109 contamination Methods 0.000 description 10
- 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 10
- 241000382455 Angelica sinensis Species 0.000 description 8
- 102100021257 Beta-secretase 1 Human genes 0.000 description 8
- 230000032683 aging Effects 0.000 description 8
- 210000003710 cerebral cortex Anatomy 0.000 description 8
- 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 8
- 210000002216 heart Anatomy 0.000 description 8
- 238000000879 optical micrograph Methods 0.000 description 8
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 7
- 230000007812 deficiency Effects 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 206010022437 insomnia Diseases 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 230000001086 cytosolic effect Effects 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 210000000952 spleen Anatomy 0.000 description 6
- 101710150192 Beta-secretase 1 Proteins 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 229960003980 galantamine Drugs 0.000 description 5
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 231100000572 poisoning Toxicity 0.000 description 5
- 230000000607 poisoning effect Effects 0.000 description 5
- 230000001737 promoting effect Effects 0.000 description 5
- 206010033557 Palpitations Diseases 0.000 description 4
- 241001619461 Poria <basidiomycete fungus> Species 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 208000002173 dizziness Diseases 0.000 description 4
- 229960003530 donepezil Drugs 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000013067 intermediate product Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 231100000915 pathological change Toxicity 0.000 description 4
- 230000036285 pathological change Effects 0.000 description 4
- HPOIPOPJGBKXIR-UHFFFAOYSA-N 3,6-dimethoxy-10-methyl-galantham-1-ene Natural products O1C(C(=CC=2)OC)=C3C=2CN(C)CCC23C1CC(OC)C=C2 HPOIPOPJGBKXIR-UHFFFAOYSA-N 0.000 description 3
- LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 239000004411 aluminium Substances 0.000 description 3
- 239000002738 chelating agent Substances 0.000 description 3
- 230000001713 cholinergic effect Effects 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 description 3
- IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229960001685 tacrine Drugs 0.000 description 3
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- 208000031091 Amnestic disease Diseases 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 241000125175 Angelica Species 0.000 description 2
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 2
- 206010010774 Constipation Diseases 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- 235000001287 Guettarda speciosa Nutrition 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 2
- 208000007443 Neurasthenia Diseases 0.000 description 2
- RDHQFKQIGNGIED-MRVPVSSYSA-N O-acetyl-L-carnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 230000006986 amnesia Effects 0.000 description 2
- 206010003549 asthenia Diseases 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 230000001914 calming effect Effects 0.000 description 2
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 description 2
- 229940074393 chlorogenic acid Drugs 0.000 description 2
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 description 2
- 235000001368 chlorogenic acid Nutrition 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 210000002503 granulosa cell Anatomy 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000002052 molecular layer Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000005728 strengthening Methods 0.000 description 2
- 230000001502 supplementing effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000035922 thirst Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 229940126680 traditional chinese medicines Drugs 0.000 description 2
- 238000003809 water extraction Methods 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 229940122041 Cholinesterase inhibitor Drugs 0.000 description 1
- 241000721047 Danaus plexippus Species 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 244000303040 Glycyrrhiza glabra Species 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017443 Hedysarum boreale Nutrition 0.000 description 1
- 235000007858 Hedysarum occidentale Nutrition 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 208000019255 Menstrual disease Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030302 Oliguria Diseases 0.000 description 1
- 235000001188 Peltandra virginica Nutrition 0.000 description 1
- 241000222341 Polyporaceae Species 0.000 description 1
- 230000002292 Radical scavenging effect Effects 0.000 description 1
- 241001558929 Sclerotium <basidiomycota> Species 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- LIRCFGBNQPWVRY-UHFFFAOYSA-K aluminum;2-methyl-4-oxopyran-3-olate Chemical compound [Al+3].CC=1OC=CC(=O)C=1[O-].CC=1OC=CC(=O)C=1[O-].CC=1OC=CC(=O)C=1[O-] LIRCFGBNQPWVRY-UHFFFAOYSA-K 0.000 description 1
- 231100000540 amenorrhea Toxicity 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
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000001947 glycyrrhiza glabra rhizome/root Substances 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000008897 memory decline Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 230000005709 nerve cell growth Effects 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000036565 night sweats Effects 0.000 description 1
- 206010029410 night sweats Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229940126673 western medicines Drugs 0.000 description 1
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)
- A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
- A61K36/725—Ziziphus, e.g. jujube
-
- 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
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
- A61K36/076—Poria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
- A61K36/605—Morus (mulberry)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Mycology (AREA)
- Botany (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The application discloses a traditional Chinese medicine preparation for preventing and treating senile dementia and a production method thereof, which belong to the field of traditional Chinese medicine preparations, and aim to overcome the defects of overhigh synthesis cost and doubtful curative effect of medicines in the prior art, the technical scheme comprises 5-10 parts of wild jujube seed, 5-10 parts of mulberry, 5-10 parts of poria cocos and 3-5 parts of Chinese angelica, the medicines are combined, the traditional Chinese medicine active ingredients are used, the synthesis cost is low, the effects of nourishing blood and tranquillizing, activating blood and relieving arthralgia, detoxifying and the like are achieved, meanwhile experiments prove that the beta secretase activity in the brain is inhibited, the alpha secretase activity is increased, the beta amyloid precursor is decomposed in the normal direction, and the beta amyloid precipitation is reduced, so that senile plaque formation is slowed down; the composition also has the effects of removing excessive harmful superoxide anion free radicals (O2) and the like, and recovering and enhancing the memory and cognitive ability of patients. Is suitable for preventing and treating AD.
Description
Technical Field
The application belongs to the field of traditional Chinese medicine preparations, and in particular relates to a traditional Chinese medicine preparation for preventing and treating senile dementia by inhibiting beta secretase activity and a production method thereof.
Background
With the development of civilization of substances, the living standard of people is higher and higher, the service life is longer and longer, and the aging is becoming a living reality. The senile aging diseases, especially senile dementia, with aging memory decline become not only the individuals of the aged but also the burden of families and the burdens of society. At present, the acceleration of the aging process, especially over 65 years, has approached the developed national level.
Senile dementia has a complex mechanism, and the medical community proposes a plurality of theories such as beta-amyloid deposition, neurofibrillary tangle, cholinergic, oxidative stress injury, genetic factors, aluminum poisoning, brain trauma and others, and the beta-amyloid precipitation theory is recognized at present. Various medical treatments come from various theories, but cannot be radically cured.
As the medicines for senile dementia commonly used clinically at present, galantamine is reported to be the one with the best effect, while donepezil is the most common cholinesterase inhibitor at present, (1) tacrine is a CHEI with central activity and reversibility, and has high fat solubility and can easily penetrate through the blood brain barrier. Studies have shown that tacrine has a certain improving effect on 30% of aging memory, thinking ability, other cognitive functions and the like, and also has a certain improving effect in certain secondary mental symptoms. The main disadvantage of tacrine is that it has a certain irritation to cholinergic of the periphery of the brain and a certain toxic effect on the liver of the patient. (2) Galanthamine, which belongs to a reversible acetylcholinesterase inhibitor, has high selectivity to AchE, and according to the research, the effective rate of galanthamine in clinical treatment and moderate aging can reach 60%. According to treatment observation of related hospitals, 80% of senile feedback galanthamine has a continuous improvement effect on cognitive functions, and can effectively relieve clinical symptoms of dementia. Galantamine has no toxicity to liver and good tolerance, and can be continuously taken for a long time. (3) Donepezil belongs to the second generation CHEI, has high selectivity, can obviously inhibit AchE in brain tissues, and has been shown by related researches that in the treatment of the senile degree exceeding 24wk, as high as 76% of patients consider that donepezil has an improvement effect on cognitive ability and whole brain function. This shows that donepezil has remarkable curative effect on treating moderate and mild aging memory, and meanwhile, the medicine has less adverse reaction and better tolerance, and does not influence the liver of a patient. Other studies were still in progress:
the nerve cell growth factor enhancer (1) potassium leptin, which is a cognition enhancer, is mostly used in the treatment of mild and moderate senile dementia, and can stimulate the growth of axons of patients, enrich the synthesis of nerve nutrition and improve the memory of the patients to a certain extent. Potassium leprinate, a drug for enhancing nerve regeneration, was the first drug to be used in phase three clinical trials. (2) Acetyl L-carnitine belongs to a cholinergic agitation drug which can permeate the blood brain barrier and can play a role in transporting the acetylcholine, and is a membrane stabilizer drug. In animal experiments, it is proved that acetyl L-carnitine has a certain protective effect on synapses of central nerves and peripheral nerves. Traditional Chinese medicine: 1 dialectical treatment, 2 acupuncture and massage method, and 3 extract.
The research progress of the medicine for treating senile senility and the beta-amyloid deposition resisting medicine is that (1) copper and zinc chelating agent is applied to mouse experiment by the researcher to find that the copper and zinc chelating agent plays the role of structure center and active center in the process of beta A4 generation and aggregation. Therefore, the copper and zinc chelating agent can also become a novel medicament for preventing and treating senile aging hypomnesis. (2) The vaccine is AN artificially synthesized beta-amyloid peptide vaccine AN-1792 which has a certain stimulation effect on the immune response of amyloid plaques of neurons in the brain, so that the amyloid plaques are decomposed, the synthesis cost of the drug is high, and the curative effect is doubtful.
Disclosure of Invention
In order to solve the problem of high cost of drug synthesis, the application aims to provide a traditional Chinese medicine preparation for preventing and treating senile dementia, which can inhibit the activity of beta secretase.
In order to achieve the above object, the technical scheme of the present application is as follows: the Chinese medicine preparation for inhibiting beta secretase activity and preventing and treating senile dementia consists of wild jujube seed 5-10 weight portions, mulberry fruit 5-10 weight portions, tuckahoe 5-10 weight portions and angelica 3-5 weight portions.
Further, the traditional Chinese medicine preparation comprises 5 parts of wild jujube seed, 5 parts of mulberry, 5 parts of poria cocos and 3 parts of Chinese angelica.
Further, the traditional Chinese medicine preparation comprises 8 parts of spina date seed, 8 parts of mulberry, 8 parts of poria cocos and 4 parts of Chinese angelica.
Further, the traditional Chinese medicine preparation comprises 10 parts of spina date seed, 10 parts of mulberry, 10 parts of poria cocos and 5 parts of Chinese angelica.
Further, the preparation forms of the traditional Chinese medicine preparation comprise pills, oral liquid, capsules, granules and tablets.
Further, the use method of the traditional Chinese medicine preparation comprises the steps of inhibiting beta secretase activity in AD brain and increasing alpha secretase activity, decomposing beta amyloid precursor in a normal direction, reducing beta amyloid precipitation and then removing harmful superoxide anion free radicals.
After the scheme is adopted, the following beneficial effects are realized: semen Ziziphi Spinosae: seed, function: nourishing heart and tranquillizing, nourishing liver and calming heart, promoting fluid production and quenching thirst, nourishing yin and tonifying kidney, nourishing liver and arresting sweating. The indications are as follows: deficiency of heart yin, palpitation, amnesia, insomnia, dreaminess, dysphoria, insomnia, dizziness due to blood deficiency, and night sweat. The dosage is as follows: 3-4 money. The wild jujube seed is a monarch drug, is matched with mulberry, poria cocos and angelica, and has obvious curative effect on treating neurasthenia mainly comprising insomnia.
Mulberry: also called mulberry fruit, sweet, sour and cold in nature, returns to heart, liver and kidney meridians, has the effects of replenishing blood, nourishing yin, promoting fluid production and moistening dryness, and is used for dizziness, tinnitus, palpitation, insomnia, premature graying hair, body fluid impairment, thirst, internal heat, diabetes and constipation due to blood deficiency;
poria is dry sclerotium of Polyporaceae fungus, has effects of removing dampness, invigorating spleen, regulating stomach, tranquilizing mind, strengthening essence, and nourishing marrow, and can be used for treating heart and spleen deficiency, heart and kidney imbalance caused by insomnia, amnesia, edema, oliguria, spleen deficiency, anorexia, phlegm, dizziness, palpitation, loose stool, diarrhea, etc.; for each side of Poria cocos and licorice root, it is necessary to take the action of treating them by Mi-Mi Hong Zhushu.
Poria has effects of invigorating spleen, eliminating dampness, relieving diarrhea, calming heart, and tranquilizing. Poria is sweet and light in taste and neutral in nature, and enters heart, spleen and kidney meridians.
Chinese angelica root: [ functional indications ] blood replenishing and regulating, menstruation regulating and pain relieving, dryness moistening and intestine smoothing. Can be used for treating blood deficiency, sallow complexion, dizziness and palpitation; blood deficiency, or menoxenia and amenorrhea with stasis; pain syndrome such as deficiency-cold type abdominal pain, coronary heart disease angina pectoris, rheumatalgia, traumatic injury and the like; constipation due to intestinal dryness; cough and asthma due to long-term cough. The influence on the hematopoietic system, early reports indicate that the infusion of angelica sinensis into mice po can significantly promote the generation of hemoglobin and red blood cells; the inhibition of central nervous system by Angelica sinensis has been reported earlier. Japanese scholars report that Japanese Taihe and Angelica sinensis (An-gelicaacutiloba Kitaglia) volatile oils have sedative, hypnotic, analgesic, anesthetic effects. The important target of the 'wild jujube seed-angelica' medicine for treating insomnia is explored through network pharmacology and molecular docking technology.
The medicines are combined, the traditional Chinese medicine active ingredients are adopted, the synthesis cost is low, the effects of nourishing blood and soothing the nerves, promoting blood circulation and removing arthralgia, detoxifying and the like are achieved, meanwhile, experiments prove that the beta secretase activity in the brain is inhibited, the alpha secretase activity is increased, the beta amyloid precursor is decomposed towards the normal direction, the beta amyloid precipitation is reduced, and the senile plaque formation is slowed down; the composition also has the effects of removing excessive harmful superoxide anion free radicals (O2) and the like, and recovering and enhancing the memory and cognitive ability of patients. Is suitable for preventing and treating AD.
The composition can be used as a prescription for preventing and treating AD, and is decocted for administration by patients; is more suitable for modern pharmaceutical enterprises to extract the active ingredients and prepare any dosage form in pharmacy such as oral liquid, capsules, granules, tablets and the like.
Drawings
FIG. 1 is an optical micrograph of a normal group;
FIG. 2 is an optical micrograph of a model group;
FIG. 3 is an optical micrograph of treatment group 1;
FIG. 4 is an optical micrograph of treatment group 2;
FIG. 5 is an optical micrograph of a brain control group (x 200);
FIG. 6 is an optical micrograph of a brain model group (x 200);
FIG. 7 is an optical micrograph of brain treatment group 1 (x 200);
figure 8 optical micrograph of brain treatment group 2 (x 200).
Detailed Description
The following is a further detailed description of the embodiments:
example 1
A Chinese medicinal preparation for inhibiting beta-secretase activity and preventing and treating senile dementia comprises 5-10 parts of wild jujube seed, 5-10 parts of mulberry, 5-10 parts of poria cocos and 3-5 parts of Chinese angelica.
Example two
The difference between this embodiment and the above embodiment is the production method of the oral liquid:
weighing semen Ziziphi Spinosae, mori fructus, poria, and radix Angelicae sinensis, decocting with 5-8 times of water twice for 2-3 hr each time, and mixing to obtain solution A.
(2) Heating and concentrating the liquid medicine A in a pot to obtain concentrated liquid B.
(3) Cooling, adding 3 times of 95% ethanol, mixing, and standing at 4-8deg.C in refrigerator or ice house for 16-24 hr. Filtering to remove precipitate.
(4) Recovering ethanol from the filtrate. And (3) placing the filtrate in an ethanol recovery device, and heating to recover ethanol. The medicine liquid after the ethanol is recovered is put into a pot to be heated and properly concentrated, and a small amount of residual ethanol is volatilized. Obtaining liquid medicine c.
(5) Taking the liquid c, adding a proper amount of syrup, uniformly mixing, filling and sterilizing to obtain the finished oral liquid.
Example III
The difference between this embodiment and the above embodiment is that this embodiment is a method for producing a capsule:
the method for extracting and precipitating the medicine with water and alcohol is the same as that of oral liquid, and liquid medicine D is obtained.
And (3) continuously heating and concentrating the solution D to obtain fluid extract E. And (5) spray drying. The intermediate product dry paste powder F is obtained.
Mixing the intermediate product F with appropriate amount of adjuvants, granulating, encapsulating, packaging with aluminum foil, and packaging to obtain the final product capsule.
Example IV
This example differs from the above examples in that this example is a method of producing granules:
the production method of the granule comprises the following steps:
the preparation method comprises the steps of carrying out water extraction and alcohol precipitation on the medicine, and obtaining dry paste powder F.
And (3) uniformly mixing the intermediate product dry paste powder F with a proper amount of auxiliary materials, granulating, drying and subpackaging to obtain the finished granules.
Example five
This embodiment differs from the above embodiment in that this embodiment is a method of producing tablets:
the method for extracting and precipitating the medicine with water and alcohol is the same as that of oral liquid, and liquid medicine D is obtained.
And (3) continuously heating and concentrating the solution D to form fluid extract E.
Mixing the intermediate product fluid extract E with appropriate amount of auxiliary granules, granulating, tabletting, and packaging to obtain the final product tablet.
The administration method comprises the following steps:
oral liquid, 2 to 3 times daily, 10ml each time. The capsule is prepared by 2 to 3 times per day, and 2 granules per day. The granule is prepared into granule, 2-3 times per day, 1 bag each time, and 7 g per bag. Tablets, 2 to 3 times per day, 2 to 3 tablets each, 0.3 grams each. Compared with the prior art, the application has the outstanding substantial characteristics and remarkable progress that:
according to the principle of combining the theory of traditional Chinese medicine and the theory of Western medicine, the traditional Chinese medicines are optimized and scientifically combined.
The preparation has the advantages of making the medicines mutually matched, supplementing the advantages and supplementing the advantages, nourishing blood and tranquillizing, promoting blood circulation and removing arthralgia, detoxifying, promoting urination, dehumidifying, strengthening spleen, treating both principal and secondary aspect of disease, accelerating the transformation and excretion of poison and protecting the functions of important organs of organisms.
The application overcomes the defects of western medicines. Under the condition of no radical cure medicine, the product is prepared from traditional Chinese medicines, has mild effect, is nontoxic and convenient to eat, and is suitable for large-area and wide prevention and treatment.
According to the results of animal experiments, the application has the advantages that the beta secretase activity in the brain is inhibited, the alpha secretase activity is increased, the beta amyloid precursor is decomposed towards the normal direction, and the beta amyloid precipitation is reduced, so that the senile plaque formation is slowed down; the composition also has the function of removing excessive harmful superoxide anion free radicals (O 2 ) Etc., restoring and enhancing the memory and cognitive abilities of the patient. Is suitable for preventing and treating AD.
1. Clinical verification shows that the basic prescription of the wild jujube decoction is modified, mainly used for nourishing blood and tranquillizing, and has obvious curative effect on neurasthenia mainly comprising insomnia.
2. The raw materials are easy to obtain, the formula is scientific, the production process is advanced, the operability is strong, the product price is moderate, and the method is suitable for industrial production.
3. According to the requirements of the properties of the active ingredients, the product adopts the production process of water extraction, alcohol precipitation and sterilization methods, has high active ingredients, is easy to be absorbed by human bodies, is not easy to deteriorate, and has long storage life.
4. The raw materials used in the application are mostly edible and medicinal, are used according to daily dosage and treatment course through acute toxicity experiments,
no toxic or side effects are found.
The following are experimental data of the application (molded with aluminum maltol):
(1) experiment one:
table 1 comparison of brain beta secretase (BACE 1), brain alpha secretase, brain gamma secretase Activity of the Experimental groups
Note that: analysis of variance, brain beta secretase 1: f=2.872, p=0.052, compared to the model set, ▲ P<0.05 ▲▲ P<0.01, the difference is statistically significant. Secretion of brain alphaEnzyme: in comparison with the set of models, ▲▲ P<the 0.01 difference is statistically significant; in comparison with the treatment group, ●● P<0.01, the difference is statistically significant. Brain gamma-secretase: f=5.661, p=0, 004, compared to the model group, ▲ P<0.05 ▲▲ P<the 0.0 difference is statistically significant. (note: treatment group is a clothes recipe)
(2) And (II) experiment:
TABLE 2 comparison of brain beta secretase Activity u/L for each experimental group
Note that: analysis of variance, brain beta secretase 1: f=3.981, p=0.018, compared to treatment 1 group, ▲▲ P<0.01, the difference is statistically significant. ( And (3) injection: the recipe 1 is taken orally and the recipe 2 is taken orally as the effective component chlorogenic acid )
(3) Third, experiment:
TABLE 3 comparison of brain beta secretase Activity u/L for each experimental group
Note that: analysis of variance, brain beta secretase 1: f=14.913, p=0.000, compared to the normal group, ▲▲ P<0.01, compared with the model group, ●● P<0.01, the difference is statistically significant. (note: treatment 1 group is the recipe of the oral administration, treatment 2 group is chlorogenic acid)
(4) Fourth experiment:
table 4 comparison of brain beta secretase Activity u/L for each experimental group
Note that: analysis of variance, brain beta secretase: f=18.295, p=0.000, compared to the treatment group, ▲▲ P<0.01, compared with the normal group, ● P<the 0.05 difference is statistically significant;
(5) fifth experiment:
table 5 comparison of mouse brain beta secretase, alpha secretase, r secretase (u/L)
Note that: analysis of variance, brain beta secretase 1: f=4.140, p=0.015, compared to the normal group, ▲ P<0.05, ▲▲ P<the 0.01 difference is statistically significant. Brain alpha secretase: f=6.828, p=0.002, compared to treatment group 2, ▲▲ P<0.01, the difference is statistically significant; brain r secretase: f=11.806, p=0.000, compared to the normal group, ▲▲ P<0.01, all differences
The meaning of the mathematics;
(6) sixth, experiment:
TABLE 6 comparison of brain beta secretase Activity u/L for each experimental group
Note that: analysis of variance, brain beta secretase 1: f=5.984, p=0.003, compared to the normal group, ▲▲ P<0.01; in comparison with the treatment group, ● P<0.05, the difference is statistically significant.
(7) Seventh, experiment:
TABLE 7 brain beta secretase Activity (BACE 1) from various aluminum concentration models and comparison
Note that: analysis of variance, β (BACE 1): f=2.453, p=0.076, compared to the medium dose group, ▲ P<0.05, the difference is statistically significant.
4. Experiment IV: results of organ pathology examination.
(1) The characteristics of normal light mirror and pathological change of a normal group, an aluminum poisoning model group and a treatment group under an experimental mirror: the rat brain was cut into paraffin-embedded sections with anterior cortex, HE stained, and observed with a microscope at 200-fold magnification. The cerebral cortex 1 photograph is the optical lens structure of the control group, and the molecular layer, the outer particle layer, the outer cone layer and the inner particle optical lens layer of the cerebral cortex of the control group are clearly demarcated, so that the number of particle cells is rich, and the number of cytoplasmic Nib bodies is large (figure 1). The cerebral cortex 2 photo is the light mirror structure of the aluminum poisoning model group, the number of the outer granular layer particles and the inner granular cells is obviously reduced due to unclear cerebral cortex layering, and the cytoplasmic Nib bodies are also reduced in number and become small in volume. There were more neurons with atrophy, degeneration (fig. 2). The cerebral cortex 3, 4 photographs are the cerebral cortex photographs of treatment group 1 and treatment group 2, respectively (fig. 3, fig. 4). It can be seen that the pathological changes of the treatment group are well improved, the number of granulosa cells is increased, the number of neuronal cytoplasmic Nib bodies is also increased and the volume is increased, wherein the pathological changes of the treatment group 2 are obviously improved.
(2) Normal mirror group under the aluminium poisoning experiment mirror, aluminium poisoning model group and treatment group's mirror normal and pathological change's characteristics:
the rat brain was cut into paraffin-embedded sections with anterior cortex, HE stained, and observed with a microscope at 200-fold magnification. 1. The structure of the lens of the control group can be seen that the molecular layer, the outer particle layer, the outer cone layer and the inner particle lens layer of the cerebral cortex of the control group (figure 5) are clearly demarcated, the number and the volume of particle cells are normal, and cytoplasmic Nib bodies are rich. 2. The structure of the lens of the aluminium intoxication model group (fig. 6) shows that the number of granular cells is significantly reduced due to the unclear cerebral cortex delamination, and cytoplasmic nieman bodies are also reduced. There are more neurons that shrink, denature and die. 3. Treatment group 2 (FIG. 7) showed a good improvement in the pathology of the treatment group, an increase in the number of granulosa cells, and an increase in neuronal cytoplasmic Nib, with the most pronounced improvement in the pathology of treatment group 4 (FIG. 8).
5. Experiment five: memory function measurement
Table 8 comparison of the time of the maze of water before, during and after the experiment (seconds/only/time)
Analysis of variance: comparison between groups, comparison between groups before modeling, P>0.05, the difference is not statistically significant. After the molding, compared with the normal group, Δ P<0.05， ΔΔ P<0.01, the difference is statistically significant. After treatment, the therapeutic effect was compared to the normal group, Δ P<0.05, the difference is statistically significant. In-group comparison, compared with the comparison before molding, a P<0.05, the difference is statistically significant.
TABLE 9 comparison of the water maze time(s) for mice of each group before, during, and after contamination
Note that: intra-group comparison: compared with the prior to the contamination of the medicine, ● p is less than 0.05. Compared with the method in the contamination of the Chinese herbal medicine, ※ p is less than 0.05; group-to-group comparison: in comparison with the normal group, ▲ P＜0.05。
table 10 comparison of the memory error Rate (%) of the water maze of mice of each group before, during and after contamination
Note that: group-to-group comparison: in comparison with the normal group, ▲ P＜0.05。
group-to-group comparison: before contamination, the water maze time and the memory error rate of each group of mice are not obviously different (P is more than 0.05); the water maze time and the memory error rate of the medium and high dose groups are obviously higher than those of the normal group (P is less than 0.05) after the infection, and the comparison difference between the low dose group and the normal group is not statistically significant (P is more than 0.05). Intra-group comparison: compared with the water maze time before the infection, the difference between the water maze time in the normal group and the low dose group before the infection has no statistical significance (P is more than 0.05), the water maze time after the infection is obviously higher than that before the infection (P is less than 0.05), and the water maze time in the middle and high dose groups before the infection is obviously higher than that before the infection (P is less than 0.05); compared with the middle contamination, the water maze time after contamination of the low, medium and high dose groups is obviously higher than that of the middle contamination (P is less than 0.05), and the difference between the water maze time after contamination of the normal group and that of the middle contamination has no statistical significance (P is more than 0.05).
6. Experiment six: other enzyme changes associated with memory
TABLE 11 brain AchE
Analysis of variance, brain AchE, compared to model set, ▲▲ P<0.01；
7. experiment seven:
TABLE 12 brainOxygen radical scavenging ratio comparison
Analysis of variance:the clearance rate, compared with the normal group, △△ p < 0.01, compared with treatment group 1, ★ P＜0.05, ★★ p is less than 0.01, compared with the treatment group 2, ▲▲ P＜0.01.；
8. experiment eight:
table 13 brain aluminum content comparison for mice of each group
Analysis of variance, brain aluminum, comparison with model set, Δ P<0.05， ΔΔ P<0.01, the difference is statistically significant.
It is noted that relational terms such as first and second, and the like are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
The foregoing is merely an embodiment of the present application, and a specific structure and characteristics of common knowledge in the art, which are well known in the scheme, are not described herein, so that a person of ordinary skill in the art knows all the prior art in the application date or before the priority date, can know all the prior art in the field, and has the capability of applying the conventional experimental means before the date, and a person of ordinary skill in the art can complete and implement the present embodiment in combination with his own capability in the light of the present application, and some typical known structures or known methods should not be an obstacle for a person of ordinary skill in the art to implement the present application. It should be noted that modifications and improvements can be made by those skilled in the art without departing from the structure of the present application, and these should also be considered as the scope of the present application, which does not affect the effect of the implementation of the present application and the utility of the patent. The protection scope of the present application is subject to the content of the claims, and the description of the specific embodiments and the like in the specification can be used for explaining the content of the claims.
Claims (6)
1. A Chinese medicinal preparation for preventing and treating senile dementia and inhibiting beta secretase activity is characterized in that: comprises 5-10 parts of wild jujube seed, 5-10 parts of mulberry, 5-10 parts of poria cocos and 3-5 parts of Chinese angelica.
2. The Chinese medicinal preparation for preventing and treating senile dementia, which inhibits the activity of beta secretase according to claim 1, is characterized in that: the traditional Chinese medicine preparation comprises 5 parts of wild jujube seed, 5 parts of mulberry, 5 parts of poria cocos and 3 parts of Chinese angelica.
3. The Chinese medicinal preparation for preventing and treating senile dementia, which inhibits the activity of beta secretase according to claim 1, is characterized in that: the traditional Chinese medicine preparation comprises 8 parts of wild jujube seed, 8 parts of mulberry, 8 parts of poria cocos and 4 parts of Chinese angelica.
4. The Chinese medicinal preparation for preventing and treating senile dementia, which inhibits the activity of beta secretase according to claim 1, is characterized in that: the traditional Chinese medicine preparation comprises 10 parts of wild jujube seed, 10 parts of mulberry, 10 parts of poria cocos and 5 parts of Chinese angelica.
5. The Chinese medicinal preparation for preventing and treating senile dementia, which inhibits the activity of beta secretase according to claim 1, is characterized in that: the preparation forms of the traditional Chinese medicine preparation comprise pills, oral liquid, capsules, granules and tablets.
6. The Chinese medicinal preparation for inhibiting beta-secretase activity and preventing and treating senile dementia as claimed in claim 5, wherein the preparation comprises the following components: the use method of the traditional Chinese medicine preparation comprises the steps of inhibiting beta secretase activity in AD brain and increasing alpha secretase activity, decomposing beta amyloid precursor towards the normal direction, reducing beta amyloid deposition, and then removing harmful superoxide anion free radicals.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311140892.0A CN117045713A (en) | 2023-09-06 | 2023-09-06 | Chinese medicinal preparation for inhibiting beta secretase activity and preventing and treating senile dementia and its production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311140892.0A CN117045713A (en) | 2023-09-06 | 2023-09-06 | Chinese medicinal preparation for inhibiting beta secretase activity and preventing and treating senile dementia and its production method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117045713A true CN117045713A (en) | 2023-11-14 |
Family
ID=88653532
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311140892.0A Pending CN117045713A (en) | 2023-09-06 | 2023-09-06 | Chinese medicinal preparation for inhibiting beta secretase activity and preventing and treating senile dementia and its production method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117045713A (en) |
-
2023
- 2023-09-06 CN CN202311140892.0A patent/CN117045713A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107126485B (en) | Traditional Chinese medicine composition for assisting in improving sleep and preparation method and application thereof | |
| CN115487239A (en) | Pharmaceutical composition for treating insomnia with anxiety and depression and preparation method thereof | |
| CN105232976B (en) | Composition for preventing or/and treating sub-health | |
| CN102988905B (en) | Traditional Chinese medicine preparation for treating epilepsia and preparation method thereof | |
| CN101049340A (en) | A pharmaceutical composition for treating vitiligo and its preparation method | |
| CN107320674B (en) | Traditional Chinese medicine composition for improving cognition and delaying progression of dementia and application thereof | |
| CN106266239A (en) | Improve compositions of memory and its preparation method and application | |
| CN104524481B (en) | A kind of Chinese medicine for treating IBS and preparation method thereof | |
| CN110772564A (en) | Traditional Chinese medicine extract composition with depression mood regulating effect, preparation method thereof and traditional Chinese medicine preparation | |
| CN102698091B (en) | Traditional Chinese medicine oral liquid for relieving neurasthenia and preparation method | |
| CN112741890B (en) | Traditional Chinese medicine composition for treating vertigo and preparation method thereof | |
| CN115487268A (en) | A composition for promoting blood circulation and toxin metabolism, and its preparation method | |
| CN117045713A (en) | Chinese medicinal preparation for inhibiting beta secretase activity and preventing and treating senile dementia and its production method | |
| CN113730499B (en) | Application of traditional Chinese medicine composition in preparation of medicine for treating alopecia areata | |
| CN113713048A (en) | Solid rhizoma gastrodiae refreshment traditional Chinese medicine composition and preparation method and application thereof | |
| CN107137504B (en) | Health food for improving sleep and enhancing immunity | |
| CN105749104A (en) | Traditional Chinese medicine preparation capable of developing intelligence and preparation method thereof | |
| CN105998752B (en) | A kind of Chinese medicine composition for the treatment of of vascular dementia | |
| CN109200191A (en) | Restrain myogenic, Chinese materia medica preparation of light speckles, beautification and white and preparation method thereof | |
| CN109758559A (en) | A kind of Chinese medicine composition and its preparation method and application for treating chronic fatigue syndrome | |
| CN109172692A (en) | A kind of compressive resistance is anti-oxidant to prevent and treat amyotrophic drug and preparation method thereof | |
| CN111388604B (en) | Traditional Chinese medicine composition for treating migraine and preparation method thereof | |
| CN110680900B (en) | Medicine for treating recurrent oral ulcer and preparation method thereof | |
| CN112089783B (en) | Application of traditional Chinese medicine composition in preparation of medicine for preventing or/and treating obesity | |
| CN107596013A (en) | A kind of extracting method of maca and its male health-care product of preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |