CA2507945A1 - Application et traitement de la maladie d'alzheimer - Google Patents
Application et traitement de la maladie d'alzheimer Download PDFInfo
- Publication number
- CA2507945A1 CA2507945A1 CA002507945A CA2507945A CA2507945A1 CA 2507945 A1 CA2507945 A1 CA 2507945A1 CA 002507945 A CA002507945 A CA 002507945A CA 2507945 A CA2507945 A CA 2507945A CA 2507945 A1 CA2507945 A1 CA 2507945A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- disease
- inhibitors
- inhibitor
- cholesterol
- 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.)
- Abandoned
Links
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 32
- 238000011282 treatment Methods 0.000 title description 14
- 230000002265 prevention Effects 0.000 title description 8
- 239000003112 inhibitor Substances 0.000 claims abstract description 76
- 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 claims abstract description 66
- 239000003613 bile acid Substances 0.000 claims abstract description 38
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 21
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 claims abstract description 9
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 claims abstract description 9
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims abstract description 6
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 30
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 230000007423 decrease Effects 0.000 claims description 10
- 230000000694 effects Effects 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 235000000346 sugar Nutrition 0.000 claims description 8
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 210000000941 bile Anatomy 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000000539 amino acid group Chemical group 0.000 claims description 4
- 150000001720 carbohydrates Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 230000000149 penetrating effect Effects 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 150000004043 trisaccharides Chemical class 0.000 claims description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 201000001883 cholelithiasis Diseases 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 208000001130 gallstones Diseases 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 2
- 230000001012 protector Effects 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA 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)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 claims 1
- 229940127328 Cholesterol Synthesis Inhibitors Drugs 0.000 claims 1
- 229940123239 Cholesterol synthesis inhibitor Drugs 0.000 claims 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 claims 1
- 102000004316 Oxidoreductases Human genes 0.000 claims 1
- 108090000854 Oxidoreductases Proteins 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000000968 intestinal effect Effects 0.000 abstract description 2
- 229940121773 Secretase inhibitor Drugs 0.000 abstract 1
- 239000000047 product Substances 0.000 description 16
- 210000004556 brain Anatomy 0.000 description 13
- 108090000765 processed proteins & peptides Proteins 0.000 description 13
- 235000005911 diet Nutrition 0.000 description 9
- 230000037213 diet Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 108010091748 peptide A Proteins 0.000 description 7
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 6
- 150000008163 sugars Chemical class 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- -1 glocosamine Chemical compound 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 208000031124 Dementia Alzheimer type Diseases 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
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102100022033 Presenilin-1 Human genes 0.000 description 2
- 108010036933 Presenilin-1 Proteins 0.000 description 2
- 102100022036 Presenilin-2 Human genes 0.000 description 2
- 108010036908 Presenilin-2 Proteins 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 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
- 230000004075 alteration Effects 0.000 description 2
- WZSDNEJJUSYNSG-UHFFFAOYSA-N azocan-1-yl-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCCCCCC2)=C1 WZSDNEJJUSYNSG-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
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000000871 hypocholesterolemic effect Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 150000002772 monosaccharides Chemical group 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical compound NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 description 1
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 101100290380 Caenorhabditis elegans cel-1 gene Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- RFSUNEUAIZKAJO-VRPWFDPXSA-N D-Fructose Natural products OC[C@H]1OC(O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-VRPWFDPXSA-N 0.000 description 1
- RGHNJXZEOKUKBD-MGCNEYSASA-N D-galactonic acid Chemical compound OC[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-MGCNEYSASA-N 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- MNQZXJOMYWMBOU-VKHMYHEASA-N D-glyceraldehyde Chemical compound OC[C@@H](O)C=O MNQZXJOMYWMBOU-VKHMYHEASA-N 0.000 description 1
- HAIWUXASLYEWLM-UHFFFAOYSA-N D-manno-Heptulose Natural products OCC1OC(O)(CO)C(O)C(O)C1O HAIWUXASLYEWLM-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-MBMOQRBOSA-N D-mannonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O RGHNJXZEOKUKBD-MBMOQRBOSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- SRBFZHDQGSBBOR-SOOFDHNKSA-N D-ribopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@@H]1O SRBFZHDQGSBBOR-SOOFDHNKSA-N 0.000 description 1
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 1
- 102100029108 Elongation factor 1-alpha 2 Human genes 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010056474 Erythrosis Diseases 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 1
- 101000841231 Homo sapiens Elongation factor 1-alpha 2 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- HSNZZMHEPUFJNZ-UHFFFAOYSA-N L-galacto-2-Heptulose Natural products OCC(O)C(O)C(O)C(O)C(=O)CO HSNZZMHEPUFJNZ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101500013104 Pelophylax ridibundus Secretoneurin Proteins 0.000 description 1
- 101800001442 Peptide pr Proteins 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- HAIWUXASLYEWLM-AZEWMMITSA-N Sedoheptulose Natural products OC[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@](O)(CO)O1 HAIWUXASLYEWLM-AZEWMMITSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 150000001320 aldopentoses Chemical class 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002788 anti-peptide Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 101150031224 app gene Proteins 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 235000020940 control diet Nutrition 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
- 229960000815 ezetimibe Drugs 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 102000046783 human APP Human genes 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- HSNZZMHEPUFJNZ-SHUUEZRQSA-N sedoheptulose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(=O)CO HSNZZMHEPUFJNZ-SHUUEZRQSA-N 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0215722 | 2002-12-12 | ||
| FR0215722A FR2848452B1 (fr) | 2002-12-12 | 2002-12-12 | Application des inhibiteurs de recapture intestinale des acides biliaires pour la prevention et le traitement de la maladie d'alzheimer |
| PCT/FR2003/003654 WO2004062652A1 (fr) | 2002-12-12 | 2003-12-10 | Application et traitement de la maladie d'alzheimer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2507945A1 true CA2507945A1 (fr) | 2004-07-29 |
Family
ID=32338722
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002507945A Abandoned CA2507945A1 (fr) | 2002-12-12 | 2003-12-10 | Application et traitement de la maladie d'alzheimer |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP1572174A1 (enExample) |
| JP (1) | JP2006514063A (enExample) |
| KR (1) | KR20050084250A (enExample) |
| CN (1) | CN1726016A (enExample) |
| AR (1) | AR042354A1 (enExample) |
| AU (1) | AU2003296802A1 (enExample) |
| BR (1) | BR0317280A (enExample) |
| CA (1) | CA2507945A1 (enExample) |
| CO (1) | CO5700712A2 (enExample) |
| FR (1) | FR2848452B1 (enExample) |
| HR (1) | HRP20050534A2 (enExample) |
| MA (1) | MA27500A1 (enExample) |
| MX (1) | MXPA05005556A (enExample) |
| NO (1) | NO20053341L (enExample) |
| NZ (1) | NZ540496A (enExample) |
| PE (1) | PE20040770A1 (enExample) |
| PL (1) | PL377110A1 (enExample) |
| RS (1) | RS20050420A (enExample) |
| RU (1) | RU2005121909A (enExample) |
| TW (1) | TW200503707A (enExample) |
| WO (1) | WO2004062652A1 (enExample) |
| ZA (1) | ZA200504656B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7521481B2 (en) | 2003-02-27 | 2009-04-21 | Mclaurin Joanne | Methods of preventing, treating and diagnosing disorders of protein aggregation |
| ZA200603165B (en) | 2003-11-03 | 2007-07-25 | Probiodrug Ag | Combinations useful for the treatment of neuronal disorders |
| CN1918131B (zh) | 2004-02-05 | 2011-05-04 | 前体生物药物股份公司 | 谷氨酰胺酰基环化酶抑制剂 |
| CA2589102C (en) | 2004-11-02 | 2013-08-13 | Northwestern University | Pyridazine compounds and methods for using the compounds to treat inflammatory diseases |
| EP2015750A2 (en) | 2006-04-28 | 2009-01-21 | Northwestern University | Compositions and treatments using pyridazine compounds and cholinesterase inhibitors |
| PL2157973T3 (pl) * | 2007-05-22 | 2015-12-31 | Otsuka Pharma Co Ltd | Lek zawierający pochodną karbostyrylu i donepezil do leczenia choroby Alzheimera |
| AU2012328453B2 (en) * | 2011-10-28 | 2017-05-04 | Shire Human Genetic Therapies, Inc. | Bile acid recycling inhibitors for treatment of hypercholemia and cholestatic liver disease |
| ES2633766T3 (es) * | 2011-10-28 | 2017-09-25 | Lumena Pharmaceuticals Llc | Inhibidores de reciclaje de ácido biliar para el tratamiento de enfermedades de hígado colestático pediátrico |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2040996A1 (en) * | 1990-05-02 | 1991-11-03 | Robert L. Albright | Composition and method for controlling cholesterol |
| AU668682B2 (en) * | 1991-02-22 | 1996-05-16 | Howard K. Shapiro | Use of pharmaceutical compounds in the treatment of symptoms of disorders related to neurological diseases and etiologically related symptomology |
| EP0910351A1 (en) * | 1996-06-27 | 1999-04-28 | G.D. Searle & Co. | Particles comprising amphiphilic copolymers, having a cross-linked shell domain and an interior core domain, useful for pharmaceutical and other applications |
| US5985936A (en) * | 1997-12-18 | 1999-11-16 | Forbes Medi-Tech, Inc. | Method of preventing and delaying onset of Alzheimer's disease and composition therefor |
| NZ505761A (en) * | 1998-01-28 | 2003-08-29 | Warner Lambert Co | Method for treating alzheimer's disease using plasma-triglceride level-lowering agents or agents that interfer with cholesterol ester synthesis |
| US6080778A (en) * | 1998-03-23 | 2000-06-27 | Children's Medical Center Corporation | Methods for decreasing beta amyloid protein |
| DE19825804C2 (de) * | 1998-06-10 | 2000-08-24 | Aventis Pharma Gmbh | 1,4-Benzothiepin-1,1-dioxidderivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| US6221897B1 (en) * | 1998-06-10 | 2001-04-24 | Aventis Pharma Deutschland Gmbh | Benzothiepine 1,1-dioxide derivatives, a process for their preparation, pharmaceuticals comprising these compounds, and their use |
| DE19845405C2 (de) * | 1998-10-02 | 2000-07-13 | Aventis Pharma Gmbh | Arylsubstituierte Propanolaminderivate und deren Verwendung |
| WO2001056579A1 (en) * | 2000-02-04 | 2001-08-09 | Esperion Therapeutics Inc. | Methods for treating alzheimer's disease |
| US20020028826A1 (en) * | 2000-06-15 | 2002-03-07 | Robl Jeffrey A. | HMG-CoA reductase inhibitors and method |
| SE0104334D0 (sv) * | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| TWI329111B (en) * | 2002-05-24 | 2010-08-21 | X Ceptor Therapeutics Inc | Azepinoindole and pyridoindole derivatives as pharmaceutical agents |
-
2002
- 2002-12-12 FR FR0215722A patent/FR2848452B1/fr not_active Expired - Fee Related
-
2003
- 2003-12-10 MX MXPA05005556A patent/MXPA05005556A/es not_active Application Discontinuation
- 2003-12-10 PL PL377110A patent/PL377110A1/pl not_active Application Discontinuation
- 2003-12-10 CN CNA2003801059727A patent/CN1726016A/zh active Pending
- 2003-12-10 CA CA002507945A patent/CA2507945A1/fr not_active Abandoned
- 2003-12-10 RU RU2005121909/15A patent/RU2005121909A/ru not_active Application Discontinuation
- 2003-12-10 RS YUP-2005/0420A patent/RS20050420A/sr unknown
- 2003-12-10 PE PE2003001247A patent/PE20040770A1/es not_active Application Discontinuation
- 2003-12-10 AU AU2003296802A patent/AU2003296802A1/en not_active Abandoned
- 2003-12-10 BR BR0317280-5A patent/BR0317280A/pt not_active IP Right Cessation
- 2003-12-10 HR HR20050534A patent/HRP20050534A2/xx not_active Application Discontinuation
- 2003-12-10 JP JP2004566119A patent/JP2006514063A/ja not_active Abandoned
- 2003-12-10 EP EP03815109A patent/EP1572174A1/fr not_active Withdrawn
- 2003-12-10 KR KR1020057010595A patent/KR20050084250A/ko not_active Withdrawn
- 2003-12-10 NZ NZ540496A patent/NZ540496A/en unknown
- 2003-12-10 AR ARP030104540A patent/AR042354A1/es not_active Application Discontinuation
- 2003-12-10 WO PCT/FR2003/003654 patent/WO2004062652A1/fr not_active Ceased
- 2003-12-11 TW TW092134949A patent/TW200503707A/zh unknown
-
2005
- 2005-06-07 ZA ZA200504656A patent/ZA200504656B/en unknown
- 2005-06-09 CO CO05056010A patent/CO5700712A2/es not_active Application Discontinuation
- 2005-06-10 MA MA28329A patent/MA27500A1/fr unknown
- 2005-07-08 NO NO20053341A patent/NO20053341L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003296802A1 (en) | 2004-08-10 |
| PE20040770A1 (es) | 2004-12-10 |
| NZ540496A (en) | 2008-04-30 |
| RU2005121909A (ru) | 2006-01-20 |
| WO2004062652A1 (fr) | 2004-07-29 |
| FR2848452A1 (fr) | 2004-06-18 |
| KR20050084250A (ko) | 2005-08-26 |
| TW200503707A (en) | 2005-02-01 |
| MXPA05005556A (es) | 2005-07-26 |
| AR042354A1 (es) | 2005-06-15 |
| BR0317280A (pt) | 2005-11-08 |
| RS20050420A (sr) | 2007-04-10 |
| HRP20050534A2 (en) | 2006-11-30 |
| MA27500A1 (fr) | 2005-08-01 |
| EP1572174A1 (fr) | 2005-09-14 |
| JP2006514063A (ja) | 2006-04-27 |
| ZA200504656B (en) | 2006-08-30 |
| PL377110A1 (pl) | 2006-01-23 |
| NO20053341L (no) | 2005-09-07 |
| CO5700712A2 (es) | 2006-11-30 |
| FR2848452B1 (fr) | 2007-04-06 |
| NO20053341D0 (no) | 2005-07-08 |
| CN1726016A (zh) | 2006-01-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2691086T3 (en) | COMPOSITIONS FOR TREATING NEUROLOGICAL DISORDERS | |
| EP1071422B1 (fr) | Associations de riluzole et de levodopa pour le traitement de la maladie de parkinson | |
| CA2507945A1 (fr) | Application et traitement de la maladie d'alzheimer | |
| EP1102586A1 (fr) | Utilisation d'extraits de ginkgo biloba pour preparer un medicament destine a traiter la sclerose laterale amyotrophique | |
| US20040138145A1 (en) | Application of intestinal biliary acid reuptake inhibitors for the prevention and treatment of alzheimer's disease | |
| FR2781671A1 (fr) | Compositions pharmaceutiques contenant un inhibiteur de la recapture de la serotonine et leur application en therapeutique | |
| WO2009092892A2 (fr) | Nouvelle composition pour traiter les effets secondaires des traitements anticancereux | |
| CN113260357B (zh) | 神经变性疾病的预防或治疗药 | |
| EP3743059B1 (fr) | Dérivés aminoacides contenant un groupement disulfanyle sous forme d'un inhibiteur de nep et d'apn pour la prévention et le traitement des douleurs relatives au nerf trijumeau | |
| EP1976496A1 (fr) | Approche therapeutique globale dans le traitement des maladies neurodegeneratives | |
| WO2025046207A1 (en) | New use of a pde 5 inhibitor combination in promoting neurite outgrowth | |
| HK1083453A (en) | Prevention and treatment of alzheimer's disease | |
| WO2024254354A1 (en) | Compositions and methods for treating refractory or intractable epilepsy | |
| WO2021021999A1 (en) | Compositions and methods for upregulation of human fetal hemoglobin | |
| FR2979543A1 (fr) | Composition pharmaceutique, nutraceutique ou alimentaire et son utilisation | |
| FR2845003A1 (fr) | Utilisation de derives de thiazolidinedione comme inhibiteurs de l'aldose reductase | |
| HK1194665B (en) | Compositions for the treatment of neurologic disorders | |
| NZ616554B2 (en) | Compositions for the treatment of neurologic disorders | |
| FR2847472A1 (fr) | Nouvelles compositions pharmaceutiques notamment pour la prevention des pathologies cardio-vasculaires |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |