CN1523016A - 吖啶衍生物及其应用 - Google Patents
吖啶衍生物及其应用 Download PDFInfo
- Publication number
- CN1523016A CN1523016A CNA031045413A CN03104541A CN1523016A CN 1523016 A CN1523016 A CN 1523016A CN A031045413 A CNA031045413 A CN A031045413A CN 03104541 A CN03104541 A CN 03104541A CN 1523016 A CN1523016 A CN 1523016A
- Authority
- CN
- China
- Prior art keywords
- amino
- pharmaceutical composition
- salt
- acridine
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 125000000641 acridinyl group Chemical class C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 title claims description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 239000002253 acid Substances 0.000 claims abstract description 33
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 25
- 206010039966 Senile dementia Diseases 0.000 claims abstract description 23
- 230000001713 cholinergic effect Effects 0.000 claims abstract description 7
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 64
- 230000002490 cerebral effect Effects 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 26
- 239000000654 additive Substances 0.000 claims description 23
- 230000000996 additive effect Effects 0.000 claims description 23
- -1 inorganic acid salt Chemical class 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 19
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 18
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 15
- 235000001968 nicotinic acid Nutrition 0.000 claims description 11
- 239000011664 nicotinic acid Substances 0.000 claims description 11
- 239000003981 vehicle Substances 0.000 claims description 11
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 10
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 10
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 10
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 10
- 150000003016 phosphoric acids Chemical class 0.000 claims description 10
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 10
- 229960001860 salicylate Drugs 0.000 claims description 10
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 claims description 9
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 9
- 108010022752 Acetylcholinesterase Proteins 0.000 claims description 8
- 229940022698 acetylcholinesterase Drugs 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 6
- 201000004810 Vascular dementia Diseases 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000000468 ketone group Chemical group 0.000 claims description 5
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical class OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 229910002651 NO3 Inorganic materials 0.000 claims description 4
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 4
- 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-M glutaminate Chemical compound [O-]C(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-M 0.000 claims description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 claims description 4
- 229940049920 malate Drugs 0.000 claims description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 claims description 4
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 4
- 230000002195 synergetic effect Effects 0.000 claims description 4
- 229940095064 tartrate Drugs 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 3
- 229940027998 antiseptic and disinfectant acridine derivative Drugs 0.000 claims description 3
- 230000008521 reorganization Effects 0.000 claims description 3
- 230000004936 stimulating effect Effects 0.000 claims description 3
- 229940124549 vasodilator Drugs 0.000 claims description 3
- 239000003071 vasodilator agent Substances 0.000 claims description 3
- 206010056677 Nerve degeneration Diseases 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 102000012440 Acetylcholinesterase Human genes 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 35
- BMRFESVZYWRROS-UHFFFAOYSA-N 1,2,3,4,5,6,7,8-octahydroacridin-9-amine Chemical compound C1CCCC2=C1N=C1CCCCC1=C2N BMRFESVZYWRROS-UHFFFAOYSA-N 0.000 abstract description 7
- 230000007074 memory dysfunction Effects 0.000 abstract description 7
- 239000002131 composite material Substances 0.000 abstract 2
- 102000003914 Cholinesterases Human genes 0.000 abstract 1
- 108090000322 Cholinesterases Proteins 0.000 abstract 1
- 229940048961 cholinesterase Drugs 0.000 abstract 1
- 239000000546 pharmaceutical excipient Substances 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 56
- 238000000034 method Methods 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 23
- 241000700159 Rattus Species 0.000 description 21
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 19
- 229940079593 drug Drugs 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000010521 absorption reaction Methods 0.000 description 13
- 230000000302 ischemic effect Effects 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 12
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 12
- 239000013641 positive control Substances 0.000 description 12
- 238000004611 spectroscopical analysis Methods 0.000 description 12
- 210000004556 brain Anatomy 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 9
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 9
- 229960002646 scopolamine Drugs 0.000 description 9
- 201000006474 Brain Ischemia Diseases 0.000 description 8
- 206010008120 Cerebral ischaemia Diseases 0.000 description 8
- 206010008118 cerebral infarction Diseases 0.000 description 8
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 210000002784 stomach Anatomy 0.000 description 8
- 102100033639 Acetylcholinesterase Human genes 0.000 description 7
- 239000002504 physiological saline solution Substances 0.000 description 7
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 6
- 229960004373 acetylcholine Drugs 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000009189 diving Effects 0.000 description 6
- 239000007928 intraperitoneal injection Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229960001685 tacrine Drugs 0.000 description 6
- GGRLKHMFMUXIOG-UHFFFAOYSA-M 2-acetyloxyethyl(trimethyl)azanium;hydroxide Chemical compound [OH-].CC(=O)OCC[N+](C)(C)C GGRLKHMFMUXIOG-UHFFFAOYSA-M 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 150000001251 acridines Chemical class 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000002146 bilateral effect Effects 0.000 description 5
- 210000001168 carotid artery common Anatomy 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 230000007087 memory ability Effects 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 238000012549 training Methods 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 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 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 241000700157 Rattus norvegicus Species 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 229940039856 aricept Drugs 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 230000005611 electricity Effects 0.000 description 4
- 230000003203 everyday effect Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 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 3
- 240000008365 Celosia argentea Species 0.000 description 3
- 235000000722 Celosia argentea Nutrition 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229940091179 aconitate Drugs 0.000 description 3
- GTZCVFVGUGFEME-UHFFFAOYSA-N aconitic acid Chemical compound OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000004534 cecum Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000000151 deposition Methods 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000002329 esterase inhibitor Substances 0.000 description 3
- 229940050411 fumarate Drugs 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 230000009191 jumping Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 239000002858 neurotransmitter agent Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 229940039748 oxalate Drugs 0.000 description 3
- 239000002574 poison Substances 0.000 description 3
- 231100000614 poison Toxicity 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 108010053652 Butyrylcholinesterase Proteins 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 102100032404 Cholinesterase Human genes 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229930195725 Mannitol Natural products 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229960001441 aminoacridine Drugs 0.000 description 2
- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000002932 cholinergic neuron Anatomy 0.000 description 2
- 230000009194 climbing Effects 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000006386 memory function Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000000116 mitigating effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 230000009182 swimming Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000008728 vascular permeability Effects 0.000 description 2
- 210000002385 vertebral artery Anatomy 0.000 description 2
- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 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
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 101100424823 Arabidopsis thaliana TDT gene Proteins 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- SDJDEDUTJZLURB-UHFFFAOYSA-N C1=CC2=NC3=CC=CC=C3C(NO3)=C2C3=C1 Chemical class C1=CC2=NC3=CC=CC=C3C(NO3)=C2C3=C1 SDJDEDUTJZLURB-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010048650 Cholinesterase inhibition Diseases 0.000 description 1
- 101800004637 Communis Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108010007979 Glycocholic Acid Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 241000233855 Orchidaceae Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010036631 Presenile dementia Diseases 0.000 description 1
- 241001620634 Roger Species 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 206010053648 Vascular occlusion Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-O acridine;hydron Chemical class C1=CC=CC2=CC3=CC=CC=C3[NH+]=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-O 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 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
- 230000006949 cholinergic function Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000005320 cranberry glass Substances 0.000 description 1
- 150000001896 cresols Chemical class 0.000 description 1
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000005786 degenerative changes Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003059 ependyma Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000012844 infrared spectroscopy analysis Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 229960003639 laurocapram Drugs 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000011169 microbiological contamination Methods 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000000272 myelencephalon Anatomy 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000004904 shortening Methods 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
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- QTENRWWVYAAPBI-YCRXJPFRSA-N streptomycin sulfate Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O QTENRWWVYAAPBI-YCRXJPFRSA-N 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000003890 succinate salts Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
- 235000019801 trisodium phosphate Nutrition 0.000 description 1
- 229940120293 vaginal suppository Drugs 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
组 别 | 第1天错误次数 | 第2天错误次数 | 第2天错误保留时间 |
正常对照组模型组阳性对照组用药组小剂量中剂量大剂量 | 2.60±2.221***10.80±5.5954.00±3.197**6.10±3.035*5.70±3.889*6.40±2.716* | 0.30±0.483**1.80±1.3171.20±0.6331.20±1.1350.60±0.843*0.80±0.422* | 256.20±71.203**131.10±110.26125.00±103.45149.30±138.16205.90±127.85121.90±115.56 |
组 别 | 大鼠学习游泳的训练时间 |
正常对照组模型组阳性对照组用药组 小剂量中剂量大剂量 | 16.305±.012***28.60±2.36627.70±5.07723.40±7.260*20.90±5.646***20.60±6.186*** |
组别(n=10) | 动物游泳路径错误次数(X±SD) |
1天 2天 3天 4天 5天 | |
假手术组模型组给药组小剂量中剂量大剂量阳性对照组 | 2.85±0.79** 0.94±0.53*** 0.19±0.11*** 0.04±0.08** 0.04±0 . 0 6 *4.34±1.05 2.34±0.97 1.88±0.96 0.86±0.73 0.41±0.443.54±0.98 2.16±0.84 1.21±085 0.70±0.56 0.32±0.633.21±0.82* 1.51±0.59* 1.02±0.70* 0.61±0.31 0.30±0.413.07±0.63** 1.35±0.74* 0.72±0.34** 0.33±0.22* 0.13±0 . 1 43.12±0.89* 1.42±0.61* 0.95±0.79* 0.37±0.39 0.20±0.17 |
组别(n=10) | 动物游到终点所需时间(秒)(X±SD) |
1天 2天 3天 4天 5天 | |
假手术组模型组给药组小剂量中剂量大剂量阳性对照组 | 53.2±14.5** 34.3±12.8** 16.1±8.80** 12.5±10.0* 10.9±3.2089.3±27.2 67.2±27.5 38.8±18.9 28.6±15.4 21.2±1 0 . 375.6±34.1 54.8±38.6 33.0±19.2 26.9±15.5 20.0±14.866.4±29.4 43.6±18.4* 22.1±11.8* 16.0±10.0* 16.2±11.661.5±24.2* 37.0±12.7* 16.9±10.2** 13.1±9.10* 12.4±6.8063.3±38.6* 39.9±15.3* 18.3±9.10** 14.2±8.75* 11.9±7.90 |
组别(n=10) | 动物学会正确游泳路径所需次数(X±SD) |
假手术组模型组给药组小剂量中剂量大剂量阳性对照组 | 17.90±9.4534.28±13.331.82±18.421.56±15.2*19.34±9.15**18.78±8.56** |
组别(n=10) | 动物在跳台实验中相关参数(X±SD) |
第1天5分钟内 第1天首次跳下 第1天3分钟内的错误次数(次) 的潜伏期(秒) 的错误次数(次) | |
假手术组模型组给药组小剂量中剂量大剂量阳性对照组 | 2.58±1.24** 158.58*±3.12*** 0.33±0.56**5.53±2.29 81.14±68.73 2.57±1.073.44±2.30 109.00±65.83 1.89±0.933.00±1.63 121.00±49.55 0.63±1.21*2.84±1.62* 153.30±0.69* 0.20±0.53**3.63±1.70 166.88±0.63** 0.25±0.46** |
组别(n=10) 脑组织含水量(%) |
正常对照组 73.99±2.62**缺血模型组 78.27±2.67给药组大剂量 76.38±3.50中剂量 74.33±4.41*大剂量 74.11±3.42** |
组 别(n=10) 脑组织染料含量(μg/g) |
正常对照组 4.95±1.12**缺血模型组 6.57±1.22给药组大剂量 5.51±1.45中剂量 5.22±1.13*大剂量 5.05±0.98** |
Claims (12)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03104541 CN1239486C (zh) | 2003-02-18 | 2003-02-18 | 吖啶衍生物及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03104541 CN1239486C (zh) | 2003-02-18 | 2003-02-18 | 吖啶衍生物及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1523016A true CN1523016A (zh) | 2004-08-25 |
CN1239486C CN1239486C (zh) | 2006-02-01 |
Family
ID=34282255
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 03104541 Expired - Lifetime CN1239486C (zh) | 2003-02-18 | 2003-02-18 | 吖啶衍生物及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1239486C (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102219740A (zh) * | 2010-09-10 | 2011-10-19 | 江苏神尔洋高科技有限公司 | 1,2,3,4,5,6,7,8-八氢-9-苯乙酰胺基吖啶及制备方法和药用用途 |
CN109651248A (zh) * | 2019-01-31 | 2019-04-19 | 长春华洋高科技有限公司 | 琥珀八氢氨吖啶新晶型及其制备方法和用途 |
CN110683987A (zh) * | 2019-01-31 | 2020-01-14 | 长春华洋高科技有限公司 | 吖啶衍生物多晶型及其制备方法和应用 |
WO2020156360A1 (zh) | 2019-01-31 | 2020-08-06 | 长春华洋高科技有限公司 | 胆碱酯酶抑制剂多晶型及其应用 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109796405A (zh) * | 2019-01-31 | 2019-05-24 | 长春华洋高科技有限公司 | 琥珀八氢氨吖啶多晶型及其制备方法 |
-
2003
- 2003-02-18 CN CN 03104541 patent/CN1239486C/zh not_active Expired - Lifetime
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102219740A (zh) * | 2010-09-10 | 2011-10-19 | 江苏神尔洋高科技有限公司 | 1,2,3,4,5,6,7,8-八氢-9-苯乙酰胺基吖啶及制备方法和药用用途 |
WO2012031534A1 (zh) * | 2010-09-10 | 2012-03-15 | 长春华洋高科技有限公司 | 1,2,3,4,5,6,7,8-八氢-9-苯乙酰胺基吖啶及制备方法和药用用途 |
CN102219740B (zh) * | 2010-09-10 | 2013-02-13 | 长春华洋高科技有限公司 | 1,2,3,4,5,6,7,8-八氢-9-苯乙酰胺基吖啶及制备方法和药用用途 |
US8722701B2 (en) | 2010-09-10 | 2014-05-13 | Changchun Huayang High Technology, Inc. | 1,2,3,4,5 6,7,8-octohydro-9-phenylacetamidoacridine, the preparation method and medical use thereof |
CN109651248A (zh) * | 2019-01-31 | 2019-04-19 | 长春华洋高科技有限公司 | 琥珀八氢氨吖啶新晶型及其制备方法和用途 |
CN110683987A (zh) * | 2019-01-31 | 2020-01-14 | 长春华洋高科技有限公司 | 吖啶衍生物多晶型及其制备方法和应用 |
WO2020156360A1 (zh) | 2019-01-31 | 2020-08-06 | 长春华洋高科技有限公司 | 胆碱酯酶抑制剂多晶型及其应用 |
CN113166064A (zh) * | 2019-01-31 | 2021-07-23 | 长春华洋高科技有限公司 | 胆碱酯酶抑制剂多晶型及其应用 |
JP2022508467A (ja) * | 2019-01-31 | 2022-01-19 | 長春華洋高科技有限公司 | コリンエステラーゼ阻害剤結晶多形及びその使用 |
JP7138799B2 (ja) | 2019-01-31 | 2022-09-16 | 長春華洋高科技有限公司 | コリンエステラーゼ阻害剤結晶多形及びその使用 |
CN113166064B (zh) * | 2019-01-31 | 2023-04-11 | 长春华洋高科技有限公司 | 胆碱酯酶抑制剂多晶型及其应用 |
Also Published As
Publication number | Publication date |
---|---|
CN1239486C (zh) | 2006-02-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20120277297A1 (en) | Pharmaceutical Composition Useful as Acetylcholinesterase Inhibitors | |
CN103087024B (zh) | 一类黄酮烷基胺类化合物、其制备方法和用途 | |
Nuckolls et al. | Tongue force and tongue motility are differently affected by unilateral vs bilateral nigrostriatal dopamine depletion in rats | |
JP4584534B2 (ja) | 胃食道逆流性疾患の治療のための材料 | |
MXPA04001462A (es) | Inhibidores de butirilcolinesterasa altamente selectivos para el tratamiento y la diagnosis de la enfermedad de alzheimer y demencias. | |
JP2021507944A (ja) | 運動ニューロン疾患を含む神経障害のための組成物および治療方法 | |
RU2451512C2 (ru) | Нейрогенез, опосредованный производным 4-ациламинориридина | |
CN1239486C (zh) | 吖啶衍生物及其应用 | |
AU2021215274B2 (en) | Targeted drug rescue with novel compositions, combinations, and methods thereof | |
US20190255017A1 (en) | Synergistic combinations of urolithins a and b for improving cognitive capacity or cognitive function | |
EP3453704B1 (en) | Phenol compound and combination of same with a benzodiazepine fused to 1,4-dihydropyridine for treating diseases of the central nervous and vascular systems | |
JP7049001B2 (ja) | N-置換グリシン化合物のリチウム塩及びその使用 | |
JP2011506353A (ja) | セロトニントランスポーター、セロトニン受容体およびノルアドレナリントランスポーターに親和性を有する化合物の治療的使用 | |
US11478467B2 (en) | Targeted drug rescue with novel compositions, combinations, and methods thereof | |
CN1138775C (zh) | 乙酰胆碱增强剂及其用途 | |
WO2009139901A2 (en) | Methods and compositions for improving cognitive function | |
KR20100092824A (ko) | 클로로젠산 또는 그의 염을 유효성분으로 포함하는 학습 장애, 기억력 장애 또는 치매의 예방 또는 치료용 약학적 조성물 | |
US20160002194A1 (en) | 1 -(dimethylamino)ethyl-substituted 6h-benzo[c]chromen-6-ones against senile dementia | |
BRPI0609276A2 (pt) | benzoxazocinas e seu uso terapêutico | |
Marschner et al. | Implementation of a functional observation battery for the assessment of postoperative well-being in rats subjected to fimbria-fornix transection | |
US7115666B2 (en) | Nitrone compounds, pharmaceutical compositions containing the same and methods for treating inflammation and neuropathic pain | |
RU2394816C1 (ru) | Нейротропное средство, обладающее антиоксидантной, противогипоксической, нейропротекторной, антиамнестической и противоукачивающей активностью и способностью улучшать когнитивные функции | |
RU2415668C2 (ru) | Способ лечения и профилактики отравлений фосфорорганическими инсектицидами (фои) | |
JP2023549249A (ja) | 新規なアミノ芳香族化合物またはその薬学的に許容可能な塩およびこれを有効成分として含む神経変性疾患の予防または治療用薬学的組成物 | |
RU2343908C1 (ru) | Средство для профилактики и лечения алкоголизма и способ его применения |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C57 | Notification of unclear or unknown address | ||
DD01 | Delivery of document by public notice |
Addressee: CHANGCHUN HUAYANG HIGH-TECH Co.,Ltd. Document name: Notice of petition for reexamination |
|
C57 | Notification of unclear or unknown address | ||
DD01 | Delivery of document by public notice |
Addressee: CHANGCHUN HUAYANG HIGH-TECH Co.,Ltd. Document name: Written decision of reexamination |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: JIANGSU SHEN'ERYANG HIGH-TECH. CO., LTD. Free format text: FORMER OWNER: CHANGCHUN HUAYANG HIGH-TECH CO., LTD. Effective date: 20101019 |
|
C41 | Transfer of patent application or patent right or utility model | ||
COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 130033 NO.8, JINCHUAN STREET, ECONOMIC AND TECHNOLOGICAL DEVELOPMENT AREA, CHANGCHUN CITY, JILIN PROVINCE TO: 225300 NO.404, SCIENCE AND TECHNOLOGY BUILDING, CHINA MEDICAL CITY, TAIZHOU CITY, JIANGSU PROVINCE |
|
TR01 | Transfer of patent right |
Effective date of registration: 20101019 Address after: 225300 No. 404, science building, China Pharmaceutical City, Jiangsu, Taizhou Patentee after: JIANGSU SHEN ER YANG HIGH TECHNOLOGY Co.,Ltd. Address before: 130033 No. 8, Jinchuan street, Changchun economic and Technological Development Zone, Jilin Patentee before: CHANGCHUN HUAYANG HIGH-TECH Co.,Ltd. |
|
CX01 | Expiry of patent term | ||
CX01 | Expiry of patent term |
Granted publication date: 20060201 |