CN112716969B - 治疗阿尔茨海默症的组合物及其制备方法、应用 - Google Patents
治疗阿尔茨海默症的组合物及其制备方法、应用 Download PDFInfo
- Publication number
- CN112716969B CN112716969B CN202110052554.6A CN202110052554A CN112716969B CN 112716969 B CN112716969 B CN 112716969B CN 202110052554 A CN202110052554 A CN 202110052554A CN 112716969 B CN112716969 B CN 112716969B
- Authority
- CN
- China
- Prior art keywords
- disease
- composition
- alzheimer
- group
- dosage
- 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.)
- Active
Links
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 54
- 239000000203 mixture Substances 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title description 6
- 241000700159 Rattus Species 0.000 claims abstract description 30
- FZAQROFXYZPAKI-UHFFFAOYSA-N anthracene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC3=CC(S(=O)(=O)Cl)=CC=C3C=C21 FZAQROFXYZPAKI-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims description 27
- 239000002775 capsule Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 229960004788 choline alfoscerate Drugs 0.000 claims 2
- SUHOQUVVVLNYQR-MRVPVSSYSA-O glycerylphosphorylcholine Chemical compound C[N+](C)(C)CCO[P@](O)(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-O 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000003931 cognitive performance Effects 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 231100000331 toxic Toxicity 0.000 claims 1
- 230000002588 toxic effect Effects 0.000 claims 1
- 238000012360 testing method Methods 0.000 abstract description 29
- 230000000694 effects Effects 0.000 abstract description 15
- SUHOQUVVVLNYQR-MRVPVSSYSA-N choline alfoscerate Chemical compound C[N+](C)(C)CCOP([O-])(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-N 0.000 abstract description 13
- 238000012347 Morris Water Maze Methods 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 230000006872 improvement Effects 0.000 abstract description 3
- 230000006399 behavior Effects 0.000 abstract description 2
- 238000013210 evaluation model Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 235000013305 food Nutrition 0.000 description 10
- 235000013376 functional food Nutrition 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 239000000463 material Substances 0.000 description 9
- -1 for example Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 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 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 239000006189 buccal tablet Substances 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 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 5
- LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 229950006238 nadide Drugs 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 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 4
- 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 4
- 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 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 230000032683 aging Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229960004640 memantine Drugs 0.000 description 4
- 230000006993 memory improvement Effects 0.000 description 4
- 235000015097 nutrients Nutrition 0.000 description 4
- 239000007909 solid dosage form Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000000544 cholinesterase inhibitor Substances 0.000 description 3
- 229960003530 donepezil Drugs 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 229960003980 galantamine Drugs 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229960004136 rivastigmine Drugs 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 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
- 102000013498 tau Proteins Human genes 0.000 description 3
- 108010026424 tau Proteins Proteins 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229940046011 buccal tablet Drugs 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000002932 cholinergic neuron Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 235000020256 human milk Nutrition 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 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
- 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 1
- 235000019489 Almond oil Nutrition 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
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 238000011565 Alzheimer-disease animal model Methods 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 235000003276 Apios tuberosa Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
- 208000024806 Brain atrophy Diseases 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000017647 Brassica oleracea var italica Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
- LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 description 1
- 208000004481 Choline Deficiency Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 240000008067 Cucumis sativus Species 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- 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 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 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
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 1
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 244000025272 Persea americana Species 0.000 description 1
- 235000008673 Persea americana Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 229930003537 Vitamin B3 Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 208000021752 choline deficiency disease Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000007370 cognitive improvement Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000003479 dental cement Substances 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000005553 drilling Methods 0.000 description 1
- 244000013123 dwarf bean Species 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000003937 effect on alzheimer disease Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical compound OC[C@H]1O[C@@](CO)(OC[C@@]2(OC[C@@]3(OC[C@@]4(OC[C@@]5(OC[C@@]6(OC[C@@]7(OC[C@@]8(OC[C@@]9(OC[C@@]%10(OC[C@@]%11(O[C@H]%12O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%12O)O[C@H](CO)[C@@H](O)[C@@H]%11O)O[C@H](CO)[C@@H](O)[C@@H]%10O)O[C@H](CO)[C@@H](O)[C@@H]9O)O[C@H](CO)[C@@H](O)[C@@H]8O)O[C@H](CO)[C@@H](O)[C@@H]7O)O[C@H](CO)[C@@H](O)[C@@H]6O)O[C@H](CO)[C@@H](O)[C@@H]5O)O[C@H](CO)[C@@H](O)[C@@H]4O)O[C@H](CO)[C@@H](O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O FTSSQIKWUOOEGC-RULYVFMPSA-N 0.000 description 1
- 229940107187 fructooligosaccharide Drugs 0.000 description 1
- BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 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
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 235000021331 green beans Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960000967 memantine hydrochloride Drugs 0.000 description 1
- 230000008897 memory decline Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 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
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229960004532 somatropin Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- UAEJRRZPRZCUBE-UHFFFAOYSA-N trimethoxyalumane Chemical compound [Al+3].[O-]C.[O-]C.[O-]C UAEJRRZPRZCUBE-UHFFFAOYSA-N 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 229940126673 western medicines Drugs 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Images
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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Hospice & Palliative Care (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供一种治疗阿尔茨海默症的组合物，其包含β‑烟酰胺单核苷酸(NMN)和L‑α‑甘油磷酸胆碱(α‑GPC)，其中，优选的含量是β‑烟酰胺单核苷酸的使用剂量为3～9mg/kg/d，L‑α‑甘油磷酸胆碱的使用剂量为8～20mg/kg/d。在经典的阿尔茨海默症药效评价模型‑‑Morris水迷宫测试模型中，本发明组合物对人工造模后大鼠的的学习和记忆行为有着明显改善作用。本发明的组合物均为食品级原料，安全可靠、可长期服用。
Description
技术领域
本发明涉及一种治疗阿尔茨海默症的组合物及其应用。
背景技术
阿尔茨海默症(以下也简称AD)是在1906年首次由德国精神病学家和神经发病学家Alzheimer Alois发现、并以其名字命名的老年痴呆，是一种慢性神经退行性疾病。阿尔茨海默症的主要临床表现为记忆力逐渐减退、认知功能发生障碍、行为异常和社交障碍等。随着人类平均寿命的增加，发病率逐年上升老年性痴呆症中有约70％为阿尔茨海默症，尚有血管性痴呆，两者并存的混合性痴呆。其主要病理特征是大脑萎缩、脑组织内老年斑、脑血管沉淀物和神经原纤维缠结。
目前的研究表明，阿尔茨海默症患者的主要病理学特征是β-淀粉样蛋白(Aβ) 聚集成老年斑，细胞内Tau蛋白异常聚集形成神经元纤维缠结(NFT)和神经元死亡。近年来，针对阿尔茨海默症的发病机制，在早期的胆碱能神经元假说、Aβ毒性假说和Tau蛋白假说等基础上，研究相对较少的炎症假说、胰岛素假说、氧化不平衡假说和基因突变假说也越来越受关注。阿尔茨海默症的具体发病机制目前尚未完全研究透彻，只是存在多种假说，包括胆碱能神经元假说、Aβ毒性假说、Tau蛋白假说、胰岛素假说、自由基损伤假说等。然而，阿尔茨海默症是由遗传因素和环境因素共同引发的一种复杂性疾病，单一的假说并不能解释阿尔茨海默症的全部发病特征。由于阿尔茨海默症的致病因素是非常复杂的。文中综述的所有假说可能并未完全将其概括，一些还处于初步研究阶段或未被发现的机制，如线粒体动力学失衡假说、Ca浓度失衡假说、小胶质细胞影响假说等也许能够丰富对阿尔茨海默症致病因素的描述。在阿尔茨海默症发病机制尚未完全研究清楚之前，针对阿尔茨海默症的治疗只能是对症治疗，这并不能从根本上治愈阿尔茨海默症患者。所以，找到可逆转疾病进程的药物才是攻克阿尔茨海默症这一疾病的关键。众多临床试验失败的教训提示单一靶点的治疗对于阿尔茨海默症这种复杂疾病很难奏效。
至今阿尔茨海默症的病因仍未得以阐明，无法研制出特效治疗药物，因此对阿尔茨海默症的治疗一直是一个十分棘手的问题。开发相关的药物一直是业界的追求方向。另外，由于阿尔茨海默症的发病率逐年上升，该病的预防性对策也非常受重视。如果能够开发可长期安全服用的具有阿尔茨海默症治疗效果的功能性食品，也存在巨大市场前景。
发明内容
本发明的目的是开发一款效果确切、安全性令人信服的治疗阿尔茨海默症的组合物，以满足可以适合长期服用并能够预防或改善阿尔茨海默症的需求。本发明的发明人经过深入研究，意外地发现将NMN和α-GPC组合使用，显示出的阿尔茨海默症的症状的治疗效果，从而完成了本发明。本发明的组合物，可以应用于制备用于治疗阿尔茨海默症的药物，或者以预防和治疗为目的的功能性食品。
具体而言，本发明提供一种治疗阿尔茨海默症的组合物，其特征在于，其包含β-烟酰胺单核苷酸(NMN)和L-α-甘油磷酸胆碱(α-GPC)，其中，β-烟酰胺单核苷酸的使用剂量为3～9mg/kg/d，L-α-甘油磷酸胆碱的使用剂量为8～20mg/kg/d。
作为本发明优选实施方式的药物制剂，可以为片剂、胶囊剂。
本发明还提供一种功能性食品，包含上述的治疗阿尔茨海默症的组合物以及可食用的辅料。
本发明的组合物，可以应用于制备用于治疗阿尔茨海默症的药物。
本发明中的NMN(Nicotinamide mononucleotide)是β-烟酰胺单核苷酸的简称，天然存在于活细胞中，是辅酶1NAD+(烟酰胺腺嘌呤二核苷酸)的前体。可适当延长寿命。真正发挥抗衰老作用的是一种称为烟酰胺腺嘌呤二核苷酸(NAD+)的重要能量代谢物。NMN是一种营养物质，市场上可以获得商品。NMN会在细胞中转化为NAD+，它归类为一种全新的维生素B3，且超越了普通维生素的功效，被认为是预防衰老和恢复年轻的补充剂。NMN本身是人体内含有的物质，存在于母乳及食物中，例如毛豆、西兰花、黄瓜、圆白菜、鳄梨、番茄等，但含量非常少(每100克中含有0.25-1.88 毫克)。生牛肉和虾等也含有非常少量的(每100克中含有0.06-0.42毫克)NMN成分。所以想要提高NMN，还要从外界直接补充。哈佛遗传教授大卫·辛克莱(David Sinclair)提出NMN有逆转衰老的功效：通过维持细胞内充足的NAD+，可以保持DNA 的自我修复能力，使年龄增长带来的DNA损伤得以有效修复，从而抑制衰老。而NMN 原料是NAD+的前体，服用NMN可以提高体内NAD+水平。但是迄今为止，尚无直接证据证实NMN的摄入能够治疗或者改善阿尔茨海默症的症状。
本发明中的α-GPC是L-α-甘油磷酸胆碱的简称，其是具有由构成细胞膜的主要磷脂PC(磷脂酰胆碱)脱去2个脂肪酸后的水溶性物质，原本在生物体内广泛存在，是存在于人的母乳及体液肿的身体成分之一，2009年的食品药品分类修订中，将L- α-甘油磷酸胆碱(有时也可以称为sn-甘油-3-磷酸胆碱)定义为食品。α-GPC为可以通过血脑屏障少数几种营养素之一，因此可以迅速的从胆碱转换为乙酰胆碱，被认为是防止胆碱缺乏、增加神经递质、促进促生长激素的分泌等的营养素。而且，由于乙酰胆碱酯酶抑制剂(AChEI)是到目前为止，临床上使用最为广泛的AD治疗药物， FDA批准用于治疗AD的5种药物中除了美金刚属于NMDA受体拮抗药外，其余4种[他克林(Tacrine)、多奈哌齐(Donepezil)、加兰他敏(Galanthamine)和卡巴拉汀 (Rivastigmine)]均属于AChEI。然而，可能是由于单纯的摄入α-GPC营养品由于机体的调控作用，不会增多乙酰胆碱含量，因此目前为止尚没有α-GPC的摄入能够治疗或者改善阿尔茨海默症的症状的报道。
然而本发明的发明人意外地发现，将NMN和α-GPC这两种内源性的营养成分组合使用，在动物模型上显示了对阿尔茨海默症的症状改善作用，提示了NMN和α-GPC 作为预防或治疗阿尔茨海默症的前景，具体可以参见实施例中的具体实施例。
作为本发明的优选的实施方式，本发明还提供一种治疗阿尔茨海默症的药物制剂，其包含上述组合物，还包含药学上可用接受的辅料。
本发明的组合物在使用时，优选制成口服给药的固体剂型来给药。作为用于口服给药的固体剂型包括胶囊剂、片剂、丸剂、散剂和颗粒剂。在这些固体剂型中，将组合物与至少一种常规惰性赋形剂(或载体)混合，如柠檬酸钠或磷酸二钙，或与下述成分混合：(a)填料或增容剂，例如，淀粉、乳糖、蔗糖、葡萄糖、甘露醇和硅酸； (b)粘合剂，例如，羟甲基纤维素、藻酸盐、明胶、聚乙烯基吡咯烷酮、蔗糖和阿拉伯胶；(c)保湿剂，例如，甘油；(d)崩解剂，例如，琼脂、碳酸钙、马铃薯淀粉或木薯淀粉、藻酸、某些复合硅酸盐、和碳酸钠；(e)缓溶剂，例如石蜡；(f)吸收加速剂，例如，季胺化合物；(g)润湿剂，例如鲸蜡醇和单硬脂酸甘油酯；(h)吸附剂，例如，高岭土；和(i)润滑剂，例如，滑石、硬脂酸钙、硬脂酸镁、固体聚乙二醇、十二烷基硫酸钠，或其混合物。胶囊剂、片剂和丸剂中，剂型也可包含缓冲剂。
固体剂型如片剂、糖丸、胶囊剂、丸剂和颗粒剂可采用包衣和壳材制备，如肠衣和其它本领域公知的材料。它们可包含不透明剂，并且，这种组合物中活性化合物的释放可以延迟的方式在消化道内的某一部分中释放。可采用的包埋组分的实例是聚合物质和蜡类物质。必要时，组合物也可与上述赋形剂中的一种或多种形成微胶囊形式。
用于口服给药的液体剂型包括药学上可接受的乳液、溶液、悬浮液、糖浆或酊剂。除了本发明组合物外，液体剂型可包含本领域中常规采用的惰性稀释剂，如水或其它溶剂，增溶剂和乳化剂，例知，乙醇、异丙醇、碳酸乙酯、乙酸乙酯、丙二醇、1,3- 丁二醇、二甲基甲酰胺以及油，特别是棉籽油、花生油、玉米胚油、橄榄油、蓖麻油和芝麻油或这些物质的混合物等。除了这些惰性稀释剂外，组合物也可包含助剂，如润湿剂、乳化剂和悬浮剂、甜味剂、矫味剂和香料。
除了本发明组合物外，悬浮液可包含悬浮剂，例如，乙氧基化异十八烷醇、聚氧乙烯山梨醇和脱水山梨醇酯、微晶纤维素、甲醇铝和琼脂或这些物质的混合物等。用于肠胃外注射的组合物可包含生理上可接受的无菌含水或无水溶液、分散液、悬浮液或乳液，和用于重新溶解成无菌的可注射溶液或分散液的无菌粉末。适宜的含水和非水载体、稀释剂、溶剂或赋形剂包括水、乙醇、多元醇及其适宜的混合物。
从服用方便角度考虑，本发明的组合物优选制成片剂或者胶囊剂。为制备本发明组合物的粉剂的片剂或胶囊，可将本发明组合物的粉剂与制剂载体混合，该载体为常用的制片剂组分，如玉米淀粉、蔗糖、山梨醇、脂肪酸、硬脂酸镁和其它药用稀释剂。
本发明的治疗阿尔茨海默症的组合物，可以与其他类的治疗阿尔茨海默症的药物合用。作为其他的疗阿尔茨海默症的药物，可举出他克林、多奈哌齐、卡巴拉汀、氢溴酸加兰他敏、美金刚、九期一等临床常见的药物。
本发明还提供一种功能性食品，包含上述的治疗阿尔茨海默症的组合物以及可食用的辅料。
由于本发明的组合物由于原料完全可食用，非常适合开发成功能食品，例如可制备成口含片、糖果、固体饮料、液体饮料形式的功能性食品。本发明的功能性食品，包含本发明的上述组合物和可食用的辅料，作为可以使用的符合相关标准的食品添加剂，例如符合中华人民共和国GB2760-2014标准的食品添加剂。
作为本发明的功能性食品的优选形式，可以举出口含片。将本发明的组合物制成口含片的方式没有特殊限制，可以使用公知的方法，例如，将本发明的组合物的造粒，添加可食用的辅料等混合，进行压片的过程。作为可食用的辅料，可以举出淀粉、蔗糖、甲基纤维素低聚果糖、茶粉、食盐、甜菊糖苷、山梨糖醇、维生素C 等，但不限于这些，只要是符合食品标准(例如中华人民共和国GB2760-2014)的辅料均可以适当添加。
本发明的原料本身的口味无刺激性，制成口含片时，不会有不良的味道，无须包衣。但如果为了利于食用、利于防止吸潮等目的，也可以包衣。从食品角度出发，优选使用海藻酸钠、黄原胶、阿拉伯胶等完全符合食品标准的辅料进行包衣。
作为本发明的功能性食品的优选形式，从食品化观感强，接受度高的角度考虑，本发明的组合物，还可以制成食品口服液的形式。作为食品口服的液体制剂的剂型有溶液、糖浆或混悬液。这些液体制剂的制备方法中，分散媒一般为水，非水溶性的赋形剂如杏仁油、油脂；作为药剂学上允许使用的填加剂包括如山梨醇、氢化食用油、甲基纤维素；还包括防腐剂如甲基或丙基P-酚；乳化剂如卵磷脂、阿拉伯橡胶：人工色素或甜味剂。
作为给药的剂量，应根据病人的年龄、体重、健康状况及剂型的不同而定。推荐的使用剂量为β-烟酰胺单核苷酸的使用剂量为3～9mg/kg/d，L-α-甘油磷酸胆碱的使用剂量为8～20mg/kg/d。但是由于本发明的原料成分均有着很强的安全性，本领域的技术人员可以根据个体需要，适当增加每一组分有效用量。
本发明的发明人通过实验动物模型，验证了本发明的组合物的治疗阿尔茨海默症的药效。具体而言，本研究中采用Morris水迷宫实验，该测试是强迫实验动物游泳，学习寻找隐藏在水中平台的实验，主要用于测试实验动物对空间位置感和方向感 (空间定位)的学习记忆能力，被广泛应用于阿尔茨海默症的药效评价研究中。本发明中，采用经典的Aβ1-40对大鼠的海马CA1区定向注射制备阿尔茨海默症动物模型，结合经典的Morris水迷宫测试模型大鼠的学习和记忆行为，从而评价给药成分的效果。结果显示，单独利用NMN灌胃大鼠没有表现出改善阿尔茨海默症的症状的现象，同样地，单独利用α-GPC灌胃大鼠也未表现出善阿尔茨海默症的症状的现象。然而当组合使用NMN和α-GPC进行灌胃时，对于模型大鼠产生了认知改善作用，提示了组合使用 NMN和α-GPC具有预防或治疗阿尔茨海默症的应用前景。
本发明的组合物与现有技术相比，存在以下明显的优势：本发明所开发的组合物的原料均为食品，是效果明确、安全性令人信服的治疗阿尔茨海默症的组合物，本发明的组合物并采用科学的动物表型验证了确切的效果，虽然其效果比照对照品的西药的药效弱，但是考虑到其特别适合以满足可以适合长期服用，可以用于预防阿尔茨海默症症状，因此有着广阔的市场前景。
附图说明
图1是实施例2中各组大鼠的逃避潜伏期结果的统计图表。
图2是实施例2中各组大鼠的穿台测试结果的统计图表。
具体实施方式
以下集合具体的实施例对本发明进行进一步详细的描述，实施例仅仅是为了说明本发明技术方案的实例，并非为了对本发明的保护范围进行任何限定。
实施例1AD实验动物模型的建立
模式动物品系选择SPF级SD大鼠，健康，雄性，体重为250g-300g，由上海南方模式生物科技发展有限公司提供。实验分组分为正常对照组、AD模型组、阳性药组、受试药组1、受试药组2、受试药组3，总共六组，每组8至11只。
除了正常对照组，采用β-淀粉样蛋白(具体为Aβ1-40，购于Sigma公司)注射至海马诱导大鼠为AD大鼠的建模方法进行建模方式。具体为：大鼠腹腔注射10％水合氯醛溶液麻醉，用量为4.5ml/kg。SD大鼠均采用1％戊巴比妥钠40μg/g腹腔内注射麻醉，麻醉后继而固定于脑立体定位仪上。按照大鼠脑立体定位图谱，以前囟为零起点，前囟后3.5mm处为穿刺点，中线右侧旁开2mm，而后牙科钻钻开颅骨，采用微量注射器自脑表面垂直进针3mm，双侧海马CA1区缓慢匀速注射Aβ1-40各10μg(1μL)，留针5min，退针后牙科水泥封闭颅骨钻孔处，缝合伤口，皮针+4.0手术缝合线缝合伤口，大腿肌肉注射庆大霉素1mg/kg。造模后恢复7d，开始灌胃喂养，正常对照组、AD模型组灌胃生理盐水，阳性药组灌胃盐酸美金刚3mg/kg/d，受试药组1灌胃β-烟酰胺单核苷酸 8mg/kg/d，受试药组2灌胃L-α-甘油磷酸胆碱10mg/kg/d，受试药组3灌胃β-烟酰胺单核苷酸8mg/kg/d以及L-α-甘油磷酸胆碱10mg/kg/d，连续给药21天后，立即进行以下四天的行为学测试。
实施例2行为学检测——Morris水迷宫模型测试
前3天进行逃避潜伏期试验，第4天撤去平台进行穿台试验。
2.1逃避潜伏期实验
所谓潜伏期实验，是指每只大鼠测试中从同一个位置入水，须有实验人员辅助大鼠缓慢入水。为了保证大鼠游泳上台环境尽量相同，注意补水保持平台距离水面2cm，大鼠入水后开始计时，找到平台并停留2秒的情况，记录时间，所耗费时间为潜伏期，超过120秒仍未找到平台也记作120秒。时间越短表明记忆改善效果越好。
2.2穿台实验
所谓穿台实验，是指在前3天水迷宫潜伏期测试之后，撤去水迷宫中的平台，记录大鼠入水后的运动轨迹，与平台位置相交一次记为一次穿台，记录每只大鼠120秒内穿台总次数，次数越多说明记忆改善效果越好。
2.3结果及分析
每只大鼠在前3天在各个象限入水4次，总共落水12次，将最终将得到的时间值汇总取平均值并四舍五入，作为该只大鼠的最终潜伏期，第4天每只大鼠在各个象限入水4次，将得到的4个数字取平均值，为该只大鼠的穿台次数。
利用统计学分析，比较模型组与正常组的上台潜伏期和穿台次数。本发明中正常对照组和AD模型组在潜伏期和穿台次数均有统计学差异，认定造模成功(p<0.05认为有统计学差异，p<0.01则认为有显著统计学差异)。实验结果显示：正常对照组和 AD模型组之间p<0.05，本发明的模型是可用的。
利用统计学分析，比较模型组与各给药分组上台潜伏期和穿台次数。
1.各组对模型大鼠逃避潜伏期的作用
各组大鼠的逃避潜伏期统计结果参见表1和图1。阳性对照组(美金刚组)显示了较明显的药效，其与正常对照组几乎达到同样的水平。受试药组1和受试药组2与 AD模型组比较未表现出功效，但是受试药组3相对于AD模型明显显现了记忆改善效果，虽然没有阳性对照组效果明显，但是其药效具有显著性差异(p<0.05)。
表1大鼠逃避潜伏期的统计表
2.各组对大鼠穿台测试的作用
各组大鼠的穿台测试的统计结果参见表2和图2。与上述的逃避潜伏期类似，受试药组1和受试药组2与AD模型组比较未表现出功效，但是受试药组3相对于AD模型明显显现了记忆改善效果，但是其药效具有显著性差异(p<0.05)。阳性对照组(美金刚组)显示了的药效没有逃避潜伏期统计明显，但是其也显示了明确的药效。
表2大鼠穿台测试的统计表
上述动物实验显示，受试组3所用的组合物显示了在治疗阿尔茨海默病中具有良好的应用前景，即，本发明的组合物具有治疗或者预防阿尔茨海默症的活性，可以用于制备治疗和预防阿尔茨海默症的药物或者功能性食品。
最后应说明的是：以上所述的各实施例仅用于说明本发明的技术方案，而非对其限制；尽管参照前述实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述实施例所记载的技术方案进行修改，或者对其中部分或全部技术特征进行等同替换；而这些修改或替换，并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。
本说明书中引用的所有出版物和专利文献引入本文作为参考，如同每个出版物或专利被分别明确指明引入本文作为参考。在不偏离本申请公开的实质和范围的情况下，可对本申请公开的各实施方案进行多种改变和用等同物替换。除非上下文中另有说明，否则本公开的实施方案的任何特征、步骤或实施方案都可以与任何其他特征、步骤或实施方案组合使用。
Claims (5)
1.一种治疗阿尔茨海默症的组合物，其特征在于，其包含β-烟酰胺单核苷酸NMN和L-α-甘油磷酸胆碱α-GPC，其中，β-烟酰胺单核苷酸的使用剂量为3～9mg/kg/d，L-α-甘油磷酸胆碱的使用剂量为8～20mg/kg/d。
2.一种治疗阿尔茨海默症的药物制剂，其特征在于，其包含权利要求1中所述的治疗阿尔茨海默症的组合物，以及药学上可用接受的辅料。
3.根据权利要求2所述的药物制剂，其为片剂、胶囊剂。
4.权利要求1所述的组合物在制备用于治疗阿尔茨海默症的药物中的应用。
5.权利要求1所述的组合物在制备用于改善脑内注射毒性Aβ多肽诱导的阿尔茨海默大鼠的认知行为的药物中的应用。
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211364070.6A CN115669929A (zh) | 2021-01-15 | 2021-01-15 | 辅助改善记忆的功能性食品其制备方法 |
| CN202110052554.6A CN112716969B (zh) | 2021-01-15 | 2021-01-15 | 治疗阿尔茨海默症的组合物及其制备方法、应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110052554.6A CN112716969B (zh) | 2021-01-15 | 2021-01-15 | 治疗阿尔茨海默症的组合物及其制备方法、应用 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211364070.6A Division CN115669929A (zh) | 2021-01-15 | 2021-01-15 | 辅助改善记忆的功能性食品其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112716969A CN112716969A (zh) | 2021-04-30 |
| CN112716969B true CN112716969B (zh) | 2022-11-29 |
Family
ID=75591505
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110052554.6A Active CN112716969B (zh) | 2021-01-15 | 2021-01-15 | 治疗阿尔茨海默症的组合物及其制备方法、应用 |
| CN202211364070.6A Pending CN115669929A (zh) | 2021-01-15 | 2021-01-15 | 辅助改善记忆的功能性食品其制备方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211364070.6A Pending CN115669929A (zh) | 2021-01-15 | 2021-01-15 | 辅助改善记忆的功能性食品其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN112716969B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115120607A (zh) * | 2022-06-07 | 2022-09-30 | 珍奥集团股份有限公司 | 核苷酸混合物在用于防治阿尔茨海默症制剂中的应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2016200507A1 (en) * | 2009-09-15 | 2016-02-18 | Cerulean Pharma Inc. | Treatment of cancer |
| WO2013086365A2 (en) * | 2011-12-09 | 2013-06-13 | Metabolon, Inc. | Biomarkers for kidney cancer and methods using the same |
| WO2017015660A1 (en) * | 2015-07-23 | 2017-01-26 | Salk Institute For Biological Studies | Prevention and treatment of aging and neurodegenerative diseases |
-
2021
- 2021-01-15 CN CN202110052554.6A patent/CN112716969B/zh active Active
- 2021-01-15 CN CN202211364070.6A patent/CN115669929A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN115669929A (zh) | 2023-02-03 |
| CN112716969A (zh) | 2021-04-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU775868B2 (en) | Anti-nausea compositions and methods | |
| US7834056B2 (en) | Pharmaceutical composition for gout | |
| US20150079206A1 (en) | Trigonelline as a muscle stimulant | |
| CN104587260B (zh) | 竹叶黄酮和壳寡糖的组合物，其制备方法和应用 | |
| WO2012142413A2 (en) | Nitrite compositions and uses thereof | |
| US20060241133A1 (en) | Electrically variable pneumatic structural element | |
| CN112716969B (zh) | 治疗阿尔茨海默症的组合物及其制备方法、应用 | |
| US6468556B1 (en) | Liver fat accumulation inhibitory composition, food additive for liver fat accumulation, inhibition, and method of inhibiting liver fat accumulation | |
| CN111936128A (zh) | 脑卒中的预防或治疗用组合物 | |
| JP5896474B2 (ja) | 認知機能改善用併用剤 | |
| NO20001717L (no) | Serotonin-inneholdende formulering for oral administrering og anvendelse av samme | |
| CN109498643A (zh) | 一种叶酸组合物及其在制备改善老年失智药物中的应用 | |
| KR20140017977A (ko) | 노년층용 비타 하이브리드 정제 및 그 제조 방법 | |
| TWI776450B (zh) | 正丁基苯酞於促進脂肪褐變、以及預防或治療脂肪肝及相關肝病變之應用 | |
| TW202308613A (zh) | 用於抑制腎功能降低或改善腎功能之組成物 | |
| KR20100015526A (ko) | 유리 구리 흡수 및 유리 구리 수준을 안전하게 낮추는데 유용한 경구용 아연 의약 | |
| WO2023000247A1 (zh) | α-细辛脑在制备预防或治疗出血性脑卒中药物中的应用 | |
| WO2024172002A1 (ja) | エルゴチオネインを含有する血管拡張用組成物 | |
| WO2024172003A1 (ja) | エルゴチオネインを含有する筋萎縮抑制用組成物及びＳｒｃチロシンキナーゼ阻害用組成物 | |
| US20020077349A1 (en) | Method of treating age-related vision impairment | |
| EP3811947A1 (en) | Composition of multivitamin for stimulating gastrointestinal system motility and preparation method therefor | |
| JP2022080787A (ja) | アルツハイマー病様症状緩和剤 | |
| JPH0449235A (ja) | 痴呆治療剤 | |
| JP2011136930A (ja) | 脳機能改善用組成物および脳機能を改善する方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Compositions for the treatment of Alzheimer's disease and their preparation methods and applications Granted publication date: 20221129 Pledgee: Bank of China Limited Liangxi Branch, Wuxi Pledgor: Jiangsu hengzhenghe Life Science Co.,Ltd. Registration number: Y2024980009784 |