EA037951B1 - Фенольное соединение и его комбинация с бензодиазепином, конденсированным с 1,4-дигидропиридином, для лечения поражений центральной нервной и сосудистой систем - Google Patents
Фенольное соединение и его комбинация с бензодиазепином, конденсированным с 1,4-дигидропиридином, для лечения поражений центральной нервной и сосудистой систем Download PDFInfo
- Publication number
- EA037951B1 EA037951B1 EA201892462A EA201892462A EA037951B1 EA 037951 B1 EA037951 B1 EA 037951B1 EA 201892462 A EA201892462 A EA 201892462A EA 201892462 A EA201892462 A EA 201892462A EA 037951 B1 EA037951 B1 EA 037951B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- disease
- central nervous
- treatment
- vascular
- active ingredient
- Prior art date
Links
- 230000002792 vascular Effects 0.000 title claims abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 22
- 201000010099 disease Diseases 0.000 title claims description 20
- -1 Phenol compound Chemical class 0.000 title abstract description 19
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title abstract description 9
- 229940049706 benzodiazepine Drugs 0.000 title abstract description 6
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 39
- 238000011282 treatment Methods 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 150000002989 phenols Chemical class 0.000 claims abstract description 6
- 239000004480 active ingredient Substances 0.000 claims description 37
- 208000024827 Alzheimer disease Diseases 0.000 claims description 17
- 206010012289 Dementia Diseases 0.000 claims description 14
- 208000018737 Parkinson disease Diseases 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- 206010008118 cerebral infarction Diseases 0.000 claims description 11
- 201000006474 Brain Ischemia Diseases 0.000 claims description 9
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 9
- 210000003169 central nervous system Anatomy 0.000 claims description 6
- 201000004810 Vascular dementia Diseases 0.000 claims description 3
- SJSJDWHYJXEJSQ-UHFFFAOYSA-N ethyl 2-methyl-4-(2-nitrophenyl)-4,11-dihydro-1h-pyrido[2,3-b][1,5]benzodiazepine-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(NC2=CC=CC=C2N=C2)=C2C1C1=CC=CC=C1[N+]([O-])=O SJSJDWHYJXEJSQ-UHFFFAOYSA-N 0.000 claims 2
- 239000000203 mixture Substances 0.000 abstract description 30
- 235000013824 polyphenols Nutrition 0.000 abstract description 20
- 230000003078 antioxidant effect Effects 0.000 abstract description 18
- 239000003963 antioxidant agent Substances 0.000 abstract description 11
- 230000009471 action Effects 0.000 abstract description 8
- 238000009472 formulation Methods 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 3
- 230000000626 neurodegenerative effect Effects 0.000 abstract description 3
- 108090000312 Calcium Channels Proteins 0.000 abstract description 2
- 102000003922 Calcium Channels Human genes 0.000 abstract description 2
- 208000012902 Nervous system disease Diseases 0.000 abstract description 2
- 208000025966 Neurological disease Diseases 0.000 abstract description 2
- 230000002424 anti-apoptotic effect Effects 0.000 abstract description 2
- 230000001910 anti-glutamatergic effect Effects 0.000 abstract description 2
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
- 230000003371 gabaergic effect Effects 0.000 abstract description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- 241001465754 Metazoa Species 0.000 description 48
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 35
- 239000000243 solution Substances 0.000 description 35
- 238000000034 method Methods 0.000 description 25
- 230000006378 damage Effects 0.000 description 23
- 150000003254 radicals Chemical class 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 230000000694 effects Effects 0.000 description 18
- 229960000935 dehydrated alcohol Drugs 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- 230000008569 process Effects 0.000 description 16
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 15
- 229960004756 ethanol Drugs 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 15
- 239000003826 tablet Substances 0.000 description 15
- 229940079593 drug Drugs 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 12
- 150000008442 polyphenolic compounds Chemical class 0.000 description 12
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 12
- 239000008186 active pharmaceutical agent Substances 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 10
- 239000008187 granular material Substances 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-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
- 206010061216 Infarction Diseases 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
- 210000004027 cell Anatomy 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000007574 infarction Effects 0.000 description 9
- 229910052742 iron Inorganic materials 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
- 230000002269 spontaneous effect Effects 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 235000006708 antioxidants Nutrition 0.000 description 8
- 239000011230 binding agent Substances 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 230000003859 lipid peroxidation Effects 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- 230000007971 neurological deficit Effects 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 230000001590 oxidative effect Effects 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical class C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 8
- 238000006993 Weiss annulation reaction Methods 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 230000001120 cytoprotective effect Effects 0.000 description 7
- 239000000796 flavoring agent Substances 0.000 description 7
- 239000011521 glass Substances 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 239000000314 lubricant Substances 0.000 description 7
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 7
- 230000000324 neuroprotective effect Effects 0.000 description 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 7
- 239000003642 reactive oxygen metabolite Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000008389 polyethoxylated castor oil Substances 0.000 description 6
- 230000001681 protective effect Effects 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- 239000011550 stock solution Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- MLACDGUOKDOLGC-UHFFFAOYSA-N 5-(2-aminoethyl)benzene-1,2,4-triol;hydron;bromide Chemical compound Br.NCCC1=CC(O)=C(O)C=C1O MLACDGUOKDOLGC-UHFFFAOYSA-N 0.000 description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 5
- 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 5
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 235000010323 ascorbic acid Nutrition 0.000 description 5
- 239000011668 ascorbic acid Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 230000034994 death Effects 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 230000003492 excitotoxic effect Effects 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 229930195712 glutamate Natural products 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 229960001375 lactose Drugs 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 229940118019 malondialdehyde Drugs 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 229940079877 pyrogallol Drugs 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000010410 reperfusion Effects 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000003765 sweetening agent Substances 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 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
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 229960005070 ascorbic acid Drugs 0.000 description 4
- 150000001557 benzodiazepines Chemical class 0.000 description 4
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 4
- 230000009920 chelation Effects 0.000 description 4
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 4
- 231100000063 excitotoxicity Toxicity 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- 210000002683 foot Anatomy 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 208000028867 ischemia Diseases 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 230000002438 mitochondrial effect Effects 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 230000000926 neurological effect Effects 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000004886 process control Methods 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 4
- 229910001220 stainless steel Inorganic materials 0.000 description 4
- 239000010935 stainless steel Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 210000003523 substantia nigra Anatomy 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- VCJCULBSFIZKLM-UHFFFAOYSA-N 1h-pyrido[3,2-c]diazepine Chemical class N1N=CC=CC2=NC=CC=C12 VCJCULBSFIZKLM-UHFFFAOYSA-N 0.000 description 3
- OHXQYFCNXHGKPJ-UHFFFAOYSA-N 1h-pyrimido[5,4-c]diazepine Chemical class N1N=CC=CC2=NC=NC=C12 OHXQYFCNXHGKPJ-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 235000016623 Fragaria vesca Nutrition 0.000 description 3
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 3
- 229930195714 L-glutamate Natural products 0.000 description 3
- 101710138657 Neurotoxin Proteins 0.000 description 3
- 230000002292 Radical scavenging effect Effects 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 102000019197 Superoxide Dismutase Human genes 0.000 description 3
- 108010012715 Superoxide dismutase Proteins 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 210000001168 carotid artery common Anatomy 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 210000005064 dopaminergic neuron Anatomy 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000015654 memory Effects 0.000 description 3
- 210000003470 mitochondria Anatomy 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 230000003961 neuronal insult Effects 0.000 description 3
- 239000002581 neurotoxin Substances 0.000 description 3
- 231100000618 neurotoxin Toxicity 0.000 description 3
- 230000036542 oxidative stress Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- IBGBGRVKPALMCQ-UHFFFAOYSA-N 3,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1O IBGBGRVKPALMCQ-UHFFFAOYSA-N 0.000 description 2
- AEVWDGXITUJOBD-UHFFFAOYSA-N 5-[(3,4-dihydroxyphenyl)methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical compound O=C1OC(C)(C)OC(=O)C1=CC1=CC=C(O)C(O)=C1 AEVWDGXITUJOBD-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 2
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 2
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 2
- 206010008089 Cerebral artery occlusion Diseases 0.000 description 2
- 208000028698 Cognitive impairment Diseases 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
- 229920002307 Dextran Polymers 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 244000307700 Fragaria vesca Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 2
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 2
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 229920005372 Plexiglas® Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102000015499 Presenilins Human genes 0.000 description 2
- 108010050254 Presenilins Proteins 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 2
- 108010054082 Sterol O-acyltransferase Proteins 0.000 description 2
- 102000019355 Synuclein Human genes 0.000 description 2
- 108050006783 Synuclein Proteins 0.000 description 2
- 238000005299 abrasion Methods 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000078 anti-malarial effect Effects 0.000 description 2
- 239000003430 antimalarial agent Substances 0.000 description 2
- 150000003934 aromatic aldehydes Chemical class 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 150000004646 arylidenes Chemical class 0.000 description 2
- 239000003637 basic solution Substances 0.000 description 2
- 238000009227 behaviour therapy Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000012925 biological evaluation Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 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
- 229960004106 citric acid Drugs 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 229960000913 crospovidone Drugs 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000007907 direct compression Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000003447 ipsilateral effect Effects 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229960001021 lactose monohydrate Drugs 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 2
- 230000004784 molecular pathogenesis Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 238000005121 nitriding Methods 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 230000004792 oxidative damage Effects 0.000 description 2
- 238000010525 oxidative degradation reaction Methods 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229960000999 sodium citrate dihydrate Drugs 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 230000006886 spatial memory Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- XJDDLMJULQGRLU-UHFFFAOYSA-N 1,3-dioxane-4,6-dione Chemical class O=C1CC(=O)OCO1 XJDDLMJULQGRLU-UHFFFAOYSA-N 0.000 description 1
- PCYGLFXKCBFGPC-UHFFFAOYSA-N 3,4-Dihydroxy hydroxymethyl benzene Natural products OCC1=CC=C(O)C(O)=C1 PCYGLFXKCBFGPC-UHFFFAOYSA-N 0.000 description 1
- 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 1
- HAKVKISCLOEBCH-UHFFFAOYSA-N 5-(diaminomethylidene)-1,3-dioxane-4,6-dione Chemical class NC(N)=C1C(=O)OCOC1=O HAKVKISCLOEBCH-UHFFFAOYSA-N 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 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 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 108020005199 Dehydrogenases Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 102000008857 Ferritin Human genes 0.000 description 1
- 108050000784 Ferritin Proteins 0.000 description 1
- 238000008416 Ferritin Methods 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 229940122459 Glutamate antagonist Drugs 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010021639 Incontinence Diseases 0.000 description 1
- 206010065973 Iron Overload Diseases 0.000 description 1
- 102000008133 Iron-Binding Proteins Human genes 0.000 description 1
- 108010035210 Iron-Binding Proteins Proteins 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000004722 NADPH Oxidases Human genes 0.000 description 1
- 108010002998 NADPH Oxidases Proteins 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920003080 Povidone K 25 Polymers 0.000 description 1
- 102000018779 Replication Protein C Human genes 0.000 description 1
- 108010027647 Replication Protein C Proteins 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920006243 acrylic copolymer Polymers 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000003496 anti-amnesic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000002253 anti-ischaemic effect Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 230000006851 antioxidant defense Effects 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 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
- 210000000269 carotid artery external Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007910 chewable tablet Substances 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
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000010224 classification analysis Methods 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000005090 crystal field Methods 0.000 description 1
- 229940109275 cyclamate Drugs 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229960000958 deferoxamine Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000002638 denervation Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 description 1
- BIABMEZBCHDPBV-UHFFFAOYSA-N dipalmitoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCC BIABMEZBCHDPBV-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 210000004002 dopaminergic cell Anatomy 0.000 description 1
- 230000007977 dopaminergic denervation Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000364 effect on atherosclerosis Effects 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000008387 emulsifying waxe Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000001073 episodic memory Effects 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 231100000318 excitotoxic Toxicity 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 230000021824 exploration behavior Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 229910001448 ferrous ion Inorganic materials 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 210000004744 fore-foot Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000000848 glutamatergic effect Effects 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000004171 ischemic cascade Effects 0.000 description 1
- 239000001282 iso-butane Substances 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- MCSIQURXZFDBJC-UHFFFAOYSA-N methyl 2-[4-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)methylamino]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OC)=CC=C1NC=C1C(=O)OC(C)(C)OC1=O MCSIQURXZFDBJC-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000003094 microcapsule Substances 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
- 239000008368 mint flavor Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- 230000003232 mucoadhesive effect Effects 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical class N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 238000011859 neuroprotective therapy Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 229940098462 oral drops Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229940050929 polyethylene glycol 3350 Drugs 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000003244 pro-oxidative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000006950 reactive oxygen species formation Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[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 HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 229940098467 rectal solution Drugs 0.000 description 1
- 238000006479 redox reaction Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.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 WTGQALLALWYDJH-MOUKNHLCSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 238000005549 size reduction Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 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
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate 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
- 239000001509 sodium citrate Substances 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000002672 stereotactic surgery Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
- 229960001685 tacrine Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 239000006068 taste-masking agent Substances 0.000 description 1
- 230000000659 thermocoagulation Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical class [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychology (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Dispersion Chemistry (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CU2016000059A CU24576B1 (es) | 2016-05-04 | 2016-05-04 | Compuesto fenólico y combinación del mismo con una benzodiazepina fusionada a 1,4-dihidropiridina para el tratamiento de afecciones del sistema nervioso central y vascular |
| PCT/CU2017/050003 WO2017190714A1 (es) | 2016-05-04 | 2017-05-03 | Compuesto fenólico y combinación del mismo con una benzodiazepina fusionada a 1,4-dihidropiridina para el tratamiento de afecciones del sistema nervioso central y vascular |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201892462A1 EA201892462A1 (ru) | 2019-07-31 |
| EA037951B1 true EA037951B1 (ru) | 2021-06-11 |
Family
ID=60202803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201892462A EA037951B1 (ru) | 2016-05-04 | 2017-05-03 | Фенольное соединение и его комбинация с бензодиазепином, конденсированным с 1,4-дигидропиридином, для лечения поражений центральной нервной и сосудистой систем |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US10722491B2 (enExample) |
| EP (1) | EP3453704B1 (enExample) |
| JP (1) | JP6997995B2 (enExample) |
| KR (1) | KR102416478B1 (enExample) |
| CN (1) | CN109476627B (enExample) |
| AR (1) | AR108370A1 (enExample) |
| AU (1) | AU2017259749C1 (enExample) |
| BR (1) | BR112018072579B1 (enExample) |
| CA (1) | CA3023073C (enExample) |
| CL (1) | CL2018003114A1 (enExample) |
| CO (1) | CO2018011927A2 (enExample) |
| CU (1) | CU24576B1 (enExample) |
| EA (1) | EA037951B1 (enExample) |
| ES (1) | ES2878579T3 (enExample) |
| MX (1) | MX384967B (enExample) |
| PH (1) | PH12018502327A1 (enExample) |
| SG (1) | SG11201809843SA (enExample) |
| WO (1) | WO2017190714A1 (enExample) |
| ZA (1) | ZA201808161B (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CU20160058A7 (es) | 2016-05-04 | 2017-12-08 | Centro De Investigación Y Desarrollo De Medicamentos (Cidem) Organizacion Superior De Desarrollo Emp | Derivado de benzodiazepina con actividad sobre el sistema nervioso central y vascular |
| JP2022504852A (ja) * | 2018-10-16 | 2022-01-13 | サバン ベンチャーズ プロプライアタリー リミテッド | 医療機器の洗浄のための装置および方法 |
| EP4082548A2 (en) * | 2019-12-26 | 2022-11-02 | Centro de Investigación y Desarrollo de Medicamentos CIDEM | Use of a benzodiazepine derivative and method of treatment of traumatic brain injury |
| CU20190114A7 (es) | 2019-12-26 | 2021-08-06 | Centro De Investig Y Desarrollo De Medicamentos Cidem | Combinación para simultáneamente incrementar la eficacia analgésica de la morfina y reducir su dependencia física |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007063444A (ja) * | 2005-08-31 | 2007-03-15 | Tdk Corp | 錯化合物及びこれを用いた光記録媒体 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5281714A (en) | 1990-08-16 | 1994-01-25 | American Home Products Corporation | N,N',N'-trisubstituted-5-bisaminomethylene-1,3-dioxane-4,6-dione inhibitors of acyl-CoA: cholesterol-acyl transferase |
| MX9204939A (es) | 1991-09-06 | 1993-03-01 | American Home Prod | Inhibidores 5-bis-aminometilen-1,3-dioxan-4,6-diona n,n',n'-trisubstituidas, de la acil coenzima a: colesterol-aciltransferasa. |
| ATE122671T1 (de) | 1992-07-17 | 1995-06-15 | Biogal Gyogyszergyar | Verfahren zur herstellung von 1,3-dioxan-4,6- dionderivaten. |
| JPH11180975A (ja) | 1997-10-13 | 1999-07-06 | Chemiprokasei Kaisha Ltd | アミノメチレンジオキサン誘導体、その製造方法および用途 |
| EP1737809B1 (en) | 2004-02-27 | 2013-09-18 | Amgen, Inc | Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders |
-
2016
- 2016-05-04 CU CU2016000059A patent/CU24576B1/es unknown
-
2017
- 2017-05-03 WO PCT/CU2017/050003 patent/WO2017190714A1/es not_active Ceased
- 2017-05-03 CN CN201780040492.9A patent/CN109476627B/zh not_active Expired - Fee Related
- 2017-05-03 US US16/098,683 patent/US10722491B2/en not_active Expired - Fee Related
- 2017-05-03 EA EA201892462A patent/EA037951B1/ru unknown
- 2017-05-03 JP JP2019510749A patent/JP6997995B2/ja not_active Expired - Fee Related
- 2017-05-03 KR KR1020187035042A patent/KR102416478B1/ko not_active Expired - Fee Related
- 2017-05-03 ES ES17732730T patent/ES2878579T3/es active Active
- 2017-05-03 BR BR112018072579-0A patent/BR112018072579B1/pt not_active IP Right Cessation
- 2017-05-03 AU AU2017259749A patent/AU2017259749C1/en not_active Ceased
- 2017-05-03 SG SG11201809843SA patent/SG11201809843SA/en unknown
- 2017-05-03 CA CA3023073A patent/CA3023073C/en active Active
- 2017-05-03 EP EP17732730.1A patent/EP3453704B1/en active Active
- 2017-05-03 MX MX2018013422A patent/MX384967B/es unknown
- 2017-05-04 AR ARP170101153A patent/AR108370A1/es unknown
-
2018
- 2018-10-31 CL CL2018003114A patent/CL2018003114A1/es unknown
- 2018-11-02 CO CONC2018/0011927A patent/CO2018011927A2/es unknown
- 2018-11-05 PH PH12018502327A patent/PH12018502327A1/en unknown
- 2018-12-03 ZA ZA2018/08161A patent/ZA201808161B/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007063444A (ja) * | 2005-08-31 | 2007-03-15 | Tdk Corp | 錯化合物及びこれを用いた光記録媒体 |
Non-Patent Citations (3)
| Title |
|---|
| BUENDIA IZASKUN; MICHALSKA PATRYCJA; NAVARRO ELISA; GAMEIRO ISABEL; EGEA JAVIER; LEÓN RAFAEL: "Nrf2–ARE pathway: An emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases", PHARMACOLOGY & THERAPEUTICS, ELSEVIER., GB, vol. 157, 1 January 1900 (1900-01-01), GB, pages 84 - 104, XP029374572, ISSN: 0163-7258, DOI: 10.1016/j.pharmthera.2015.11.003 * |
| DELPHINE VIVIER, ISMAIL BEN SOUSSIA, NUNO RODRIGUES, ST�PHANE LOLIGNIER, MA�LY DEVILLIERS, FRANCK C. CHATELAIN, LAETITIA PRIVAL, E: "Development of the First Two-Pore Domain Potassium Channel TWIK-Related K + Channel 1-Selective Agonist Possessing in Vivo Antinociceptive Activity", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 60, no. 3, 9 February 2017 (2017-02-09), pages 1076 - 1088, XP055394873, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b01285 * |
| SANDHU, H.S. ; SAPRA, S. ; GUPTA, M. ; NEPALI, K. ; GAUTAM, R. ; YADAV, S. ; KUMAR, R. ; JACHAK, S.M. ; CHUGH, M. ; GUPTA, M.K. ; : "Synthesis and biological evaluation of arylidene analogues of Meldrum's acid as a new class of antimalarial and antioxidant agents", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 18, no. 15, 1 August 2010 (2010-08-01), AMSTERDAM, NL, pages 5626 - 5633, XP027534396, ISSN: 0968-0896 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CU24576B1 (es) | 2022-02-04 |
| JP2019516791A (ja) | 2019-06-20 |
| KR20210025138A (ko) | 2021-03-09 |
| AU2017259749A1 (en) | 2018-12-20 |
| CL2018003114A1 (es) | 2019-06-14 |
| CA3023073C (en) | 2022-08-30 |
| EA201892462A1 (ru) | 2019-07-31 |
| EP3453704A1 (en) | 2019-03-13 |
| CO2018011927A2 (es) | 2019-02-08 |
| US10722491B2 (en) | 2020-07-28 |
| ES2878579T3 (es) | 2021-11-19 |
| BR112018072579B1 (pt) | 2024-02-20 |
| CU20160059A7 (es) | 2017-12-08 |
| AU2017259749B2 (en) | 2021-08-19 |
| MX384967B (es) | 2025-03-14 |
| WO2017190714A1 (es) | 2017-11-09 |
| MX2018013422A (es) | 2019-08-16 |
| CN109476627B (zh) | 2021-06-15 |
| JP6997995B2 (ja) | 2022-02-04 |
| BR112018072579A2 (pt) | 2019-02-19 |
| AR108370A1 (es) | 2018-08-15 |
| CN109476627A (zh) | 2019-03-15 |
| PH12018502327A1 (en) | 2019-09-02 |
| CA3023073A1 (en) | 2017-11-09 |
| EP3453704B1 (en) | 2021-06-16 |
| ZA201808161B (en) | 2021-10-27 |
| AU2017259749C1 (en) | 2021-12-02 |
| US20190133996A1 (en) | 2019-05-09 |
| SG11201809843SA (en) | 2018-12-28 |
| KR102416478B1 (ko) | 2022-07-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2019526571A (ja) | 認知症の処置 | |
| EA025735B1 (ru) | Способ лечения портальной гипертензии с использованием l-орнитина в сочетании по меньшей мере с одним из соединений, выбранных из фенилацетата и фенилбутирата | |
| AU2017259749C1 (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 | |
| HU211478A9 (en) | Pharmaceutical composition and process for the preparation thereof | |
| US8987285B2 (en) | Pharmaceutical compositions, dosage forms and new forms of the compound of formula (I), and methods of use thereof | |
| RU2738648C2 (ru) | Применение соединения для лечения хронической тревоги или острой тревоги | |
| CA2432543A1 (en) | Combination drugs | |
| EA015483B1 (ru) | ПРИМЕНЕНИЕ ИНГИБИТОРА p38 КИНАЗЫ ДЛЯ ЛЕЧЕНИЯ ПСИХИАТРИЧЕСКИХ РАССТРОЙСТВ | |
| WO2023123468A1 (zh) | 心脑血管药物及其应用 | |
| KR102428383B1 (ko) | 중추신경계 및 혈관계에 대한 활성을 가진 벤조디아제핀 생성물 | |
| KR20250005055A (ko) | 아스피린 및 기타 nsaid의 고 침투성 전구약물을 이용한 심혈관 질환의 예방 또는 치료 | |
| HK1261881B (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 | |
| HK1261881A1 (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 | |
| RU2506950C2 (ru) | Комбинация карбостирила и карнитина | |
| CA3111271A1 (en) | Pharmaceutical preparations of sebacoyl dinalbuphine and acetaminophen and methods for treating pain | |
| EA046099B1 (ru) | Применение продукта на основе бензодиазепина с активностью для профилактики и лечения деменции | |
| EA041342B1 (ru) | Применение продукта на основе бензодиазепина с активностью для профилактики и лечения болезни паркинсона | |
| EA044367B1 (ru) | Продукт на основе бензодиазепина с активностью на невропатическую боль | |
| JP2001213771A (ja) | 脳血管障害に基づく疾患の予防又は治療薬 | |
| HK1225292A1 (en) | Laquinimod combination therapy for treatment of multiple sclerosis |