CN117442632A - 罗汉果苷v在制备改善阿尔兹海默病学习记忆能力的药物中的应用 - Google Patents
罗汉果苷v在制备改善阿尔兹海默病学习记忆能力的药物中的应用 Download PDFInfo
- Publication number
- CN117442632A CN117442632A CN202311567790.7A CN202311567790A CN117442632A CN 117442632 A CN117442632 A CN 117442632A CN 202311567790 A CN202311567790 A CN 202311567790A CN 117442632 A CN117442632 A CN 117442632A
- Authority
- CN
- China
- Prior art keywords
- mogroside
- preparation
- disease
- alzheimer
- learning
- 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
- GHBNZZJYBXQAHG-KUVSNLSMSA-N (2r,3r,4s,5s,6r)-2-[[(2r,3s,4s,5r,6r)-6-[[(3s,8s,9r,10r,11r,13r,14s,17r)-17-[(2r,5r)-5-[(2s,3r,4s,5s,6r)-4,5-dihydroxy-3-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@H](CC[C@@H](C)[C@@H]1[C@]2(C[C@@H](O)[C@@]3(C)[C@H]4C(C([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]6[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O6)O)O5)O)CC4)(C)C)=CC[C@H]3[C@]2(C)CC1)C)C(C)(C)O)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GHBNZZJYBXQAHG-KUVSNLSMSA-N 0.000 title claims abstract description 63
- TVJXHJAWHUMLLG-UHFFFAOYSA-N mogroside V Natural products CC(CCC(OC1OC(COC2OC(CO)C(O)C(O)C2OC3OC(CO)C(O)C(O)C3O)C(O)C(O)C1O)C(C)(C)O)C4CCC5(C)C6CC=C7C(CCC(OC8OC(COC9OC(CO)C(O)C(O)C9O)C(O)C(O)C8O)C7(C)C)C6(C)C(O)CC45C TVJXHJAWHUMLLG-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 57
- 239000003814 drug Substances 0.000 title claims abstract description 46
- 230000013016 learning Effects 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 230000015654 memory Effects 0.000 title claims abstract description 26
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 claims abstract description 26
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 claims abstract description 26
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 claims abstract description 26
- 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 claims abstract description 23
- 239000007924 injection Substances 0.000 claims description 10
- 238000002347 injection Methods 0.000 claims description 10
- 230000007087 memory ability Effects 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 2
- 238000010253 intravenous injection Methods 0.000 claims description 2
- 229940100691 oral capsule Drugs 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 241000699670 Mus sp. Species 0.000 abstract description 31
- 108090000623 proteins and genes Proteins 0.000 abstract description 10
- 102000004169 proteins and genes Human genes 0.000 abstract description 8
- 238000011160 research Methods 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000033001 locomotion Effects 0.000 description 8
- 239000003826 tablet Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 229960001031 glucose Drugs 0.000 description 4
- 239000007902 hard capsule Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- -1 patches Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 229940032147 starch Drugs 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241001409321 Siraitia grosvenorii Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 229960001855 mannitol Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- 102100029470 Apolipoprotein E Human genes 0.000 description 2
- 101710095339 Apolipoprotein E Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000012347 Morris Water Maze Methods 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 235000011171 Thladiantha grosvenorii Nutrition 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 230000006933 amyloid-beta aggregation Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 230000006999 cognitive decline Effects 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000002662 enteric coated tablet Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000008717 functional decline Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 239000008299 semisolid dosage form Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
- 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 description 1
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 235000009815 Momordica Nutrition 0.000 description 1
- 241000218984 Momordica Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 230000005913 Notch signaling pathway Effects 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000004156 Wnt signaling pathway Effects 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 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
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000007792 alzheimer disease pathology Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000007131 anti Alzheimer effect Effects 0.000 description 1
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229940095672 calcium sulfate Drugs 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 238000000556 factor analysis Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000006951 hyperphosphorylation Effects 0.000 description 1
- 230000035874 hyperreactivity Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930189775 mogroside Natural products 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000007507 senile plaque formation Effects 0.000 description 1
- 208000022288 senile plaque formation Diseases 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229960002668 sodium chloride Drugs 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000006886 spatial memory Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 230000031836 visual learning Effects 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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)
- A61K36/42—Cucurbitaceae (Cucumber family)
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (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)
- Molecular Biology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，具体是罗汉果苷V通过减少淀粉样蛋白前体蛋白在制备改善阿尔兹海默病学习记忆能力的药物中的应用。本发明研究表明，罗汉果苷V能显著减少APP蛋白的表达水平、能有效改善AD小鼠的运动能力、能有效改善AD小鼠的学习记忆能力。
Description
【技术领域】
本发明属于治疗阿尔兹海默病药物技术领域，涉及罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，具体是罗汉果苷V通过减少淀粉样蛋白前体蛋白在制备改善阿尔兹海默病学习记忆能力的药物中的应用。
【背景技术】
阿尔茨海默病(Alzheimer’s disease，AD)是一种发生于脑部、以渐进性的认知和记忆障碍、人格异常为主要特征的常见的神经退行性疾病，占老年痴呆的60％～80％，并且被认为是世界上第六大死亡原因。目前，已经确定了20多种促进疾病进展的病理因素。三个重要的假说被认为是AD病理学的根本原因，其包括乙酰胆碱缺乏、淀粉样β老年斑的形成和tau蛋白过度磷酸化。除这些关键因素外，病理因素如载脂蛋白E(APOE)、糖原合成酶激酶3β、Notch信号通路、Wnt信号通路等，被认为在AD的进展中起作用，但目前的AD治疗只对疾病早期的认知和功能下降提供有限的缓解，迄今尚无治愈方法，且会导致一系列不良反应，全球抗AD药物在临床中屡遭失败，临床成功率极低，作用于单一途径的药物都不太可能减轻导致AD的复杂病理级联反应，有必要探索新的治疗途径、研发新药物。
β淀粉样蛋白沉积斑块是由脑组织胞间β淀粉样蛋白沉积形成的，其形成的原因是由于基因突变(已知相关基因有Lys670-Asn，Met671-Leu基因等)导致β淀粉样蛋白的前体蛋白(amyloid precursor protein，APP)的结构和功能发生改变，导致脑脊液中长期含有高浓度的β淀粉样蛋白，在物理沉降和蛋白质凝结作用下形成斑块状沉淀。遗传学、生物化学和行为学研究表明，由连续淀粉样前体蛋白(APP)蛋白水解产生的神经毒性Aβ肽是AD发展的关键步骤。APP是一种在脑内高水平表达的单次跨膜蛋白，通过一系列连续的蛋白酶以快速和高度复杂的方式代谢，包括膜内γ-分泌酶复合物，其还处理其他关键调节分子。
罗汉果(Siraitia grosvenorii)是一种发现于中国南部地区著名的食药用植物。Mogroside I、III、IV和V是从罗汉果中提取的一组具有药理生物活性的三萜类成分，具有抗氧化、抗高血糖、免疫、镇咳和抗细胞毒活性。罗汉果苷V(Mogroside V，MV)是研究最充分和最常见的形式之一，已被报道可减轻炎症和高反应性，并抑制高血糖诱导的肺癌细胞迁移和侵袭。MV在中枢神经系统疾病中的保护作用日益受到人们的关注。在非竞争性NMDA受体拮抗剂地佐西平MK801诱导的类精神分裂症小鼠模型中，MV可以通过促进神经突生长、抑制细胞凋亡和[Ca2+]i释放减少来拯救精神分裂症相关的行为表型。
因此，研究MV是否能够通过减少淀粉样蛋白前体蛋白改善阿尔兹海默症学习记忆能力的作用，具有很好的市场前景。
【发明内容】
针对目前的阿尔茨海默病治疗只对疾病早期的认知和功能下降提供有限的缓解，迄今尚无治愈方法，且会导致一系列不良反应，本发明提供了罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，具体是罗汉果苷V(简称MV)通过减少淀粉样蛋白前体蛋白在制备改善阿尔兹海默病学习记忆能力的药物中的应用。
本发明的目的通过以下技术方案来实现：
罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用。
进一步的，所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，具体是罗汉果苷V通过减少淀粉样蛋白前体蛋白在制备改善阿尔兹海默病学习记忆能力的药物中的应用。
进一步的，所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，所述药物是药物组合物，是以罗汉果苷V为主要活性成分，加上药学中可接受的辅料或辅助性成分制备成临床上可接受的药物制剂，所述的罗汉果苷V在药物组合物中的含量通常为0.01-95.0％(w/w)。
通常而言，作为药物，均是在制备成制剂后才临床应用。本发明所述的药物，作为药物组合物可根据本领域公知的方法制备，可通过将本发明药物与一种或多种药学上可接受的固体或液体赋形剂和/或辅剂结合，制成适于人或动物使用的任何剂型。
进一步的，所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，所述药物制剂包括口服制剂和注射制剂两种剂型。
进一步的，所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，所述口服制剂为口服胶囊，所述注射制剂为静脉注射液。
本发明所述药物或药物组合物可以单位剂量形式给药，给药途径可为肠道或非肠道，如口服、静脉注射、肌肉注射、皮下注射、鼻腔、口腔粘膜、眼、肺和呼吸道、皮肤、阴道、直肠等。
给药剂型可以是液体剂型、固体剂型或半固体剂型。液体剂型可以是溶液剂(包括真溶液和胶体溶液)、乳剂(包括o/w型、w/o型和复乳)、混悬剂、注射剂(包括水针剂、粉针剂和输液)、滴眼剂、滴鼻剂、洗剂和搽剂等；固体剂型可以是片剂(包括普通片、肠溶片、含片、分散片、咀嚼片、泡腾片、口腔崩解片)、胶囊剂(包括硬胶囊、软胶囊、肠溶胶囊)、颗粒剂、散剂、微丸、滴丸、栓剂、膜剂、贴片、气(粉)雾剂、喷雾剂等；半固体剂型可以是软膏剂、凝胶剂、糊剂等。
本发明药物可以制成普通制剂、也可以制成缓释制剂、控释制剂、靶向制剂及各种微粒给药系统。为了将本发明药物制成片剂，可以广泛使用本领域公知的各种赋形剂，包括稀释剂、黏合剂、润湿剂、崩解剂、润滑剂、助流剂。稀释剂可以是淀粉、糊精、蔗糖、葡萄糖、乳糖、甘露醇、山梨醇、木糖醇、微晶纤维素、硫酸钙、磷酸氢钙、碳酸钙等；润湿剂可以是水、乙醇、异丙醇等；黏合剂可以是淀粉浆、糊精、糖浆、蜂蜜、葡萄糖溶液、微晶纤维素、阿拉伯胶浆、明胶浆、羧甲基纤维素钠、甲基纤维素、羟丙基甲基纤维素、乙基纤维素、丙烯酸树脂、卡波姆、聚乙烯吡咯烷酮、聚乙二醇等；崩解剂可以是干淀粉、微晶纤维素、低取代羟丙基纤维素、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠、羧甲基淀粉钠、碳酸氢钠与枸橼酸、聚氧乙烯山梨糖醇脂肪酸酯、十二烷基磺酸钠等；润滑剂和助流剂可以是滑石粉、二氧化硅、硬脂酸盐、酒石酸、液体石蜡、聚乙二醇等。
还可以将片剂进一步制成包衣片，例如糖包衣片、薄膜包衣片、肠溶包衣片，或双层片和多层片。
为了将给药单元制成胶囊剂，可以将有效成分本发明药物与稀释剂、助流剂混合，将混合物直接置于硬胶囊或软胶囊中。也可将有效成分本发明药物先与稀释剂、黏合剂、崩解剂制成颗粒或微丸，再置于硬胶囊或软胶囊中。用于制备本发明药物片剂的各稀释剂、黏合剂、润湿剂、崩解剂、助流剂品种也可用于制备本发明药物的胶囊剂。
为将本发明药物制成注射剂，可以用水、乙醇、异丙醇、丙二醇或它们的混合物作溶剂并加入适量本领域常用的增溶剂、助溶剂、pH调剂剂、渗透压调节剂。增溶剂或助溶剂可以是泊洛沙姆、卵磷脂、羟丙基-β-环糊精等；pH调剂剂可以是磷酸盐、醋酸盐、盐酸、氢氧化钠等；渗透压调节剂可以是氯化钠、甘露醇、葡萄糖、磷酸盐、醋酸盐等。如制备冻干粉针剂，还可加入甘露醇、葡萄糖等作为支撑剂。
此外，如需要，也可以向药物制剂中添加着色剂、防腐剂、香料、矫味剂或其他添加剂。
和现有技术相比，本发明具有如下优点：
1、本发明所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，研究发现罗汉果苷V通过减少淀粉样蛋白前体蛋白来改善阿尔兹海默病学习记忆能力。
2、本发明所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，实验研究发现，通过水迷宫实验、旷场实验及细胞实验检测结果证明，MV对阿尔兹海默病模型小鼠的学习记忆能力及运动能力具有明显的改善作用，同时，在阿尔兹海默病细胞模型中发现，MV可以明显减少淀粉样蛋白前体蛋白的表达。
3、本发明所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，研究发现MV作为来源于纯天然的食药用植物罗汉果的主要成分之一，具有抗氧化、抗高血糖、免疫、镇咳等作用，对胃肠道等身体其他部位的不良反应较小。
4、本发明所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，作为来源于纯天然的食药用植物罗汉果的主要成分之一，MV的来源充足，因此用药成本较低。
【附图说明】
图1是本发明实验例中罗汉果苷V显著减少APP蛋白的表达水平的图；
图2是本发明实验例中罗汉果苷V有效改善AD小鼠的运动能力的图；
图3是本发明实验例中罗汉果苷V有效改善AD小鼠的学习记忆能力的图。
【具体实施方式】
以下结合实施例对本发明的具体实施方式做进一步说明。
实施例1：
罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用：
按照现有的工艺要求，制备成硬胶囊。
实施例2：
罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用：
按照现有的工艺要求，制备成注射剂。
实验例：
1、罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用：
2、材料与方法
2.1细胞培养与处理
含10％胎牛血清的DMEM/F12培养基(Gibco,New York,USA)培养过表达APP的人神经母细胞瘤细胞(SH-SY5Y-APP细胞)，用于Western blotting检测；利用1μg/mL DOX诱导APP表达24h后，向过表达APP蛋白的细胞培养基中添加DMSO溶解的MV，使其终浓度分别为25μM、50μM和100μM；将细胞分为5个组，Blank组、APP组、MV25μM、MV50μM组和MV100μM组，用MV处理细胞48h，进行后续Western blotting检测；
2.2Western blotting实验
按照细胞质蛋白制备试剂盒(Applygen，北京，中国)的说明收集并裂解经MV不同浓度梯度处理的细胞；细胞被分离并聚集到不同的管中；使用BCA蛋白定量试剂盒(ThermoFisher Scientific,Massachusetts,USA)评估蛋白浓度；然后用SDS-PAGE分离各组分20μg蛋白，将蛋白转移到PVDF膜上；然后用5％脱脂奶粉封闭，分别加入抗APP、抗β-actin抗体，孵育过夜；将相应的荧光二抗与一抗室温结合1h；经过四次清洗后，于ODYSSEY成像系统(LI-COR，Nebraska，USA)帮助扫描膜；
2.3动物和处理
20只8月龄雄性转基因(APP/PS1)AD小鼠及10只雄性同窝对照小鼠购自江苏艾菱菲生物科技有限公司；本研究的所有实验均按照中国桂林医学院实验动物伦理委员会的指导原则进行；将小鼠分为Con组、AD组、MV干预组，每组各10只；DMSO溶解MV；基于MV药代动力学参数和优秀的生物利用度，对MV干预组小鼠以2.5mg/kg的剂量进行MV灌胃4周，Con组及AD组进行相同体积生理盐水灌胃4周；灌胃结束后，采用旷场实验记录小鼠平均运动速度，评价小鼠自主运动能力，利用水迷宫实验检测小鼠上台潜伏期评价小鼠空间学习记忆能力；
2.4行为学训练及检测
2.4.1旷场实验
MV灌胃4周后进行旷场实验；旷场实验：记录小鼠在50cm x 50cm x 50cm旷场箱内自由运动10min的运动轨迹及平均运动速度；
2.4.2水迷宫实验
利用上海欣软信息科技有限公司Morris水迷宫(Morris water maze,MWM，XR-XM101)，沿着池边的四个极点将水箱均分成4个象限，将一个隐藏平台放置在一个象限的中点，进行连续5天的定位航行实验，将小鼠放入水箱，记录小鼠找到平台的时间，即为逃避潜伏期，每只小鼠每天训练3次，每次最多持续60s，60s内末找到平台的小鼠被引导到平台，停留20s，逃避潜伏期记录为60s；
2.5统计分析
数据以均数±标准差表示；使用GraphPad Prism软件9.0(GraphPad,California,USA)进行统计分析；采用单因素方差分析(One-way ANOVA)进行组间差异评估，然后采用Tukey的多重比较检验；P<0.05认为有统计学意义；
3、结果
3.1MV显著减少APP蛋白的表达水平
Western blotting实验结果显示，与Blank组相比，DOX诱导后，APP蛋白出现明显过表达；与DOX诱导的APP组相比，不同浓度MV处理的SH-SY5Y-APP细胞48小时后，APP单纯蛋白表达明显下降，且成浓度依赖性下降，其中，100μM MV处理组细胞中APP蛋白表达显著下降(P<0.05)(图1)；
图1MV显著减少APP蛋白的表达水平；
A Western blotting实验结果显示APP及β-actin蛋白表达条带结果；B对APP及β-actin蛋白条带的灰度扫描结果；Blank：未添加DOX；APP：添加DOX；MV25：添加DOX 24h后进行25μM MV处理细胞；MV50：添加DOX 24h后进行50μM MV处理细胞；MV100：添加DOX 24h后进行100μM MV处理细胞；n＝3，*p<0.05，****p<0.0001；
3.2MV有效改善AD小鼠的运动能力
采用旷场实验评估动物的自主运动能力，与对照组相比，AD组小鼠在记录时间内平均运动速度下降，而MV干预的AD小鼠平均运动速度明显得到恢复(图2)；
图2MV有效改善AD小鼠的运动能力；
旷场实验记录小鼠10min的平均运动速度统计结果；Con：同窝对照小鼠；AD：生理盐水灌胃的AD小鼠；MV：MV灌胃的AD小鼠；n＝10，**p<0.01；
3.3MV有效改善AD小鼠的学习记忆能力
采用水迷宫实验评估小鼠的学习记忆能力，与对照组相比，AD小鼠逃避潜伏期显著增加(P<0.05)；与AD小鼠相比，MV组小鼠逃避潜伏期显著降低(P<0.05)(图3)表明其学习记忆能力明显改善；
图3MV有效改善AD小鼠的学习记忆能力；
水迷宫实验小鼠的上台潜伏期；n＝10，AD与WT相比，****p<0.0001；AD与AD-MV相比，##P<0.01。
上述说明是针对本发明较佳可行实施例的详细说明，但实施例并非用以限定本发明的专利申请范围，凡本发明所提示的技术精神下所完成的同等变化或修饰变更，均应属于本发明所涵盖专利范围。
Claims (5)
1.罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用。
2.罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，其特征在于：罗汉果苷V通过减少淀粉样蛋白前体蛋白在制备改善阿尔兹海默病学习记忆能力的药物中的应用。
3.根据权利要求1所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，其特征在于：所述的药物是药物组合物，是以罗汉果苷V为主要活性成分，加上药学中可接受的辅料或辅助性成分制备成临床上可接受的药物制剂，所述的罗汉果苷V在药物组合物中的含量通常为0.01-95.0％w/w。
4.根据权利要求3所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，其特征在于：所述药物制剂包括口服制剂和注射制剂两种剂型。
5.根据权利要求4所述的罗汉果苷V在制备改善阿尔兹海默病学习记忆能力的药物中的应用，其特征在于：所述口服制剂为口服胶囊，所述注射制剂为静脉注射液。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311567790.7A CN117442632A (zh) | 2023-11-23 | 2023-11-23 | 罗汉果苷v在制备改善阿尔兹海默病学习记忆能力的药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311567790.7A CN117442632A (zh) | 2023-11-23 | 2023-11-23 | 罗汉果苷v在制备改善阿尔兹海默病学习记忆能力的药物中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117442632A true CN117442632A (zh) | 2024-01-26 |
Family
ID=89590958
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311567790.7A Pending CN117442632A (zh) | 2023-11-23 | 2023-11-23 | 罗汉果苷v在制备改善阿尔兹海默病学习记忆能力的药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117442632A (zh) |
-
2023
- 2023-11-23 CN CN202311567790.7A patent/CN117442632A/zh active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106456658A (zh) | 硒有机化合物的组合物和其使用方法 | |
| WO2001015717A1 (fr) | Agents contenant du ginseng destines a proteger les cellules cerebrales ou les cellules nerveuses | |
| CN114599670B (zh) | 一种角蛋白bd-13、制法和其药物组合物与用途 | |
| CN101134042A (zh) | 七叶皂苷的药物组合物及其制备方法和其用途 | |
| CN114599671B (zh) | 一种角蛋白bd-10、制法和其药物组合物与用途 | |
| RU2727142C2 (ru) | Бисамидное производное дикарбоновой кислоты в качестве средства, стимулирующего регенерацию тканей и восстановление сниженных функций тканей | |
| WO2021083206A1 (zh) | 一种角蛋白bd-17、制法和其药物组合物与用途 | |
| CN117442632A (zh) | 罗汉果苷v在制备改善阿尔兹海默病学习记忆能力的药物中的应用 | |
| WO2018166494A1 (zh) | 苦参碱衍生物在治疗糖尿病中的用途 | |
| CN118201611A (zh) | 一种含有依达拉奉右莰醇组合物在治疗认知障碍中的应用 | |
| CN114599673B (zh) | 一种角蛋白bd-6、制法和其药物组合物与用途 | |
| CN114599672B (zh) | 一种角蛋白bd-11、制法和其药物组合物与用途 | |
| JP2001139483A (ja) | 薬用人蔘からなる脳細胞または神経細胞保護剤 | |
| WO2021009768A1 (en) | An oral pharmaceutical composition for alpha- amylase inhibition | |
| WO2024074110A1 (zh) | 一种角蛋白yk93-5、制法和其药物组合物与用途 | |
| CN110623955A (zh) | Wnk激酶抑制剂在预防和/或治疗高原病中的用途 | |
| WO2024074104A1 (zh) | 一种角蛋白yk93-8、制法和其药物组合物与用途 | |
| CN114599669B (zh) | 一种角蛋白bd-4、制法和其药物组合物与用途 | |
| CN112773791B (zh) | 一种s1p抑制剂在制备治疗神经退行性疾病药物中的应用 | |
| WO2024074107A1 (zh) | 一种角蛋白yk93-2、制法和其药物组合物与用途 | |
| CN112724224B (zh) | 一种角蛋白bd-15、制法和其药物组合物与用途 | |
| CN112724232B (zh) | 一种角蛋白bd-2、制法和其药物组合物与用途 | |
| CN111317746B (zh) | 一种富勒烯结构在制备治疗阿尔茨海默病的药物中的应用 | |
| CN112724230B (zh) | 一种角蛋白bd-3、制法和其药物组合物与用途 | |
| CN112724228B (zh) | 一种角蛋白bd-14、制法和其药物组合物与用途 |
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 |