SK4198A3 - Use of 1,4-dihydropyridine derivatives in the prevention and therapy of atherosclerotic degradation of arterial walls - Google Patents
Use of 1,4-dihydropyridine derivatives in the prevention and therapy of atherosclerotic degradation of arterial walls Download PDFInfo
- Publication number
- SK4198A3 SK4198A3 SK41-98A SK4198A SK4198A3 SK 4198 A3 SK4198 A3 SK 4198A3 SK 4198 A SK4198 A SK 4198A SK 4198 A3 SK4198 A3 SK 4198A3
- Authority
- SK
- Slovakia
- Prior art keywords
- lercanidipine
- medicament
- compound
- preparation
- use according
- Prior art date
Links
- 230000003143 atherosclerotic effect Effects 0.000 title claims abstract description 15
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title abstract description 15
- 230000015556 catabolic process Effects 0.000 title abstract description 3
- 238000006731 degradation reaction Methods 0.000 title abstract description 3
- 230000002265 prevention Effects 0.000 title description 3
- 238000002560 therapeutic procedure Methods 0.000 title 1
- ZDXUKAKRHYTAKV-UHFFFAOYSA-N lercanidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZDXUKAKRHYTAKV-UHFFFAOYSA-N 0.000 claims abstract description 51
- 229960004294 lercanidipine Drugs 0.000 claims abstract description 50
- 239000003814 drug Substances 0.000 claims abstract description 20
- ZDXUKAKRHYTAKV-XIFFEERXSA-N 5-o-[1-[3,3-diphenylpropyl(methyl)amino]-2-methylpropan-2-yl] 3-o-methyl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound C1([C@@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC([N+]([O-])=O)=C1 ZDXUKAKRHYTAKV-XIFFEERXSA-N 0.000 claims abstract description 7
- ZDXUKAKRHYTAKV-MGBGTMOVSA-N 5-o-[1-[3,3-diphenylpropyl(methyl)amino]-2-methylpropan-2-yl] 3-o-methyl (4r)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound C1([C@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC([N+]([O-])=O)=C1 ZDXUKAKRHYTAKV-MGBGTMOVSA-N 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 29
- -1 2-nitrophenyl Chemical group 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 238000007911 parenteral administration Methods 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
- 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 abstract description 51
- 108010007622 LDL Lipoproteins Proteins 0.000 abstract description 28
- 102000007330 LDL Lipoproteins Human genes 0.000 abstract description 28
- 210000000107 myocyte Anatomy 0.000 abstract description 23
- 238000000034 method Methods 0.000 abstract description 22
- 210000002540 macrophage Anatomy 0.000 abstract description 14
- 230000005012 migration Effects 0.000 abstract description 8
- 238000013508 migration Methods 0.000 abstract description 8
- 230000008569 process Effects 0.000 abstract description 7
- 230000035755 proliferation Effects 0.000 abstract description 7
- 238000011161 development Methods 0.000 abstract description 5
- 230000001590 oxidative effect Effects 0.000 abstract description 4
- 230000004060 metabolic process Effects 0.000 abstract description 3
- 231100000216 vascular lesion Toxicity 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000012986 modification Methods 0.000 abstract 1
- 230000004048 modification Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 35
- 235000012000 cholesterol Nutrition 0.000 description 22
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 21
- 230000000694 effects Effects 0.000 description 20
- 230000003647 oxidation Effects 0.000 description 18
- 238000007254 oxidation reaction Methods 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000011534 incubation Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 238000005886 esterification reaction Methods 0.000 description 12
- 239000002609 medium Substances 0.000 description 12
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 11
- 150000001840 cholesterol esters Chemical class 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 230000032050 esterification Effects 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 201000001320 Atherosclerosis Diseases 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 102000004895 Lipoproteins Human genes 0.000 description 5
- 108090001030 Lipoproteins Proteins 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 230000003276 anti-hypertensive effect Effects 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000012894 fetal calf serum Substances 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- JPXPPUOCSLMCHK-UHFFFAOYSA-N 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid Chemical compound COC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 JPXPPUOCSLMCHK-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 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 4
- 241000282412 Homo Species 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 125000006501 nitrophenyl group Chemical group 0.000 description 4
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 210000003024 peritoneal macrophage Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010003210 Arteriosclerosis Diseases 0.000 description 3
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000004872 arterial blood pressure Effects 0.000 description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 230000003399 chemotactic effect Effects 0.000 description 3
- 239000005515 coenzyme Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 210000000497 foam cell Anatomy 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 102000057234 Acyl transferases Human genes 0.000 description 2
- 108700016155 Acyl transferases Proteins 0.000 description 2
- 239000012983 Dulbecco’s minimal essential medium Substances 0.000 description 2
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229930006000 Sucrose Natural products 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
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000035508 accumulation Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000001266 acyl halides Chemical class 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 244000309466 calf Species 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 150000001993 dienes Chemical class 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000002900 effect on cell Effects 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000000686 essence Substances 0.000 description 2
- 238000010931 ester hydrolysis Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 229960004340 lacidipine Drugs 0.000 description 2
- GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 description 2
- 230000006372 lipid accumulation Effects 0.000 description 2
- 230000003859 lipid peroxidation Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 210000002254 renal artery Anatomy 0.000 description 2
- 206010038464 renal hypertension Diseases 0.000 description 2
- 102000014452 scavenger receptors Human genes 0.000 description 2
- 108010078070 scavenger receptors Proteins 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- ZQPPMHVWECSIRJ-JVBZJRCZSA-N (z)-octadec-9-enoic acid Chemical compound CCCCCCCC\C=C/CCCCCCC[14C](O)=O ZQPPMHVWECSIRJ-JVBZJRCZSA-N 0.000 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- XHTYQFMRBQUCPX-UHFFFAOYSA-N 1,1,3,3-tetramethoxypropane Chemical compound COC(OC)CC(OC)OC XHTYQFMRBQUCPX-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- MQWDISMNBYOLAB-UHFFFAOYSA-N 1-[3,3-diphenylpropyl(methyl)amino]-2-methylpropan-2-ol Chemical compound C=1C=CC=CC=1C(CCN(C)CC(C)(C)O)C1=CC=CC=C1 MQWDISMNBYOLAB-UHFFFAOYSA-N 0.000 description 1
- GUXKBDHITFXEJG-UHFFFAOYSA-N 5-methoxycarbonylpyridine-3-carboxylic acid Chemical compound COC(=O)C1=CN=CC(C(O)=O)=C1 GUXKBDHITFXEJG-UHFFFAOYSA-N 0.000 description 1
- 229940123324 Acyltransferase inhibitor Drugs 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular 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
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 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
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 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
- 229920003106 Methocel™ A4C Polymers 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 1
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical class [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007997 Tricine buffer Substances 0.000 description 1
- 206010072810 Vascular wall hypertrophy Diseases 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002404 acyltransferase inhibitor Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012911 assay medium Substances 0.000 description 1
- 230000036523 atherogenesis Effects 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 238000003516 cell number determination Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 230000001637 coronarodilatory effect Effects 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 210000004177 elastic tissue Anatomy 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 235000004626 essential fatty acids Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940118019 malondialdehyde Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 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
- 239000008363 phosphate buffer Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 108700038606 rat Smooth muscle Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000015590 smooth muscle cell migration Effects 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- YZYDOFGGDSDUPX-UHFFFAOYSA-M sodium;carbonic acid;chloride Chemical compound [Na+].[Cl-].OC(O)=O YZYDOFGGDSDUPX-UHFFFAOYSA-M 0.000 description 1
- FVAUCKIRQBBSSJ-FXMLPJBTSA-M sodium;iodine-125(1-) Chemical compound [Na+].[125I-] FVAUCKIRQBBSSJ-FXMLPJBTSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 229940071127 thioglycolate Drugs 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—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
-
- 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
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- 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
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI951513A IT1275532B (it) | 1995-07-14 | 1995-07-14 | Uso di derivati 1,4-diidropiridinici per la prevenzione e la terapia della degenerazione aterosclerotica della parete arteriosa |
| PCT/EP1996/002872 WO1997003669A1 (en) | 1995-07-14 | 1996-06-28 | Use of 1,4-dihydropyridine derivatives in the prevention and therapy of atherosclerotic degradation of arterial walls |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK4198A3 true SK4198A3 (en) | 1998-05-06 |
Family
ID=11371972
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK41-98A SK4198A3 (en) | 1995-07-14 | 1996-06-28 | Use of 1,4-dihydropyridine derivatives in the prevention and therapy of atherosclerotic degradation of arterial walls |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP0839036B1 (de) |
| JP (1) | JPH11509214A (de) |
| KR (1) | KR19990028741A (de) |
| CN (1) | CN1190345A (de) |
| AT (1) | ATE183644T1 (de) |
| AU (1) | AU690471B2 (de) |
| CA (1) | CA2219501A1 (de) |
| CZ (1) | CZ11698A3 (de) |
| DE (1) | DE69603968T2 (de) |
| DK (1) | DK0839036T3 (de) |
| ES (1) | ES2138359T3 (de) |
| GR (1) | GR3031096T3 (de) |
| HU (1) | HUP9802736A3 (de) |
| IL (1) | IL122302A (de) |
| IT (1) | IT1275532B (de) |
| NO (1) | NO980171L (de) |
| SK (1) | SK4198A3 (de) |
| WO (1) | WO1997003669A1 (de) |
| ZA (1) | ZA965924B (de) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6852737B2 (en) | 2001-08-06 | 2005-02-08 | Recordati Ireland Limited | Crude and crystalline forms of lercanidipine hydrochloride |
| ITMI20011726A1 (it) * | 2001-08-06 | 2003-02-06 | Recordati Ind Chimica E Farma | Forme polimorfe della lercanidipina cloridrato |
| TW200613275A (en) * | 2004-08-24 | 2006-05-01 | Recordati Ireland Ltd | Lercanidipine salts |
| AR053023A1 (es) * | 2005-02-25 | 2007-04-18 | Recordati Ireland Ltd | Base libre de lercanidipina, metodos para su preparacion y composiciones farmaceuticas que las contienen |
| EP2585051B2 (de) | 2010-06-23 | 2020-04-08 | KRKA, tovarna zdravil, d.d., Novo mesto | Pharmazeutische orale dosierformen mit lercandipin und enalapril und ihren pharmazeutisch akzeptablen salzen |
| PT2627173E (pt) | 2010-10-12 | 2015-07-24 | Medicines Co | Formulações de clevidipina em emulsão contendo agentes antimicrobianos |
| US8658676B2 (en) | 2010-10-12 | 2014-02-25 | The Medicines Company | Clevidipine emulsion formulations containing antimicrobial agents |
| EP2654729B1 (de) | 2010-12-24 | 2016-05-04 | KRKA, d.d., Novo mesto | Orale homogene pharmazeutische zubereitung enthaltend lercanidipine und enalapril oder ihre pharmazeutische salze zusammen mit einer organischen säure |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8403866D0 (en) * | 1984-02-14 | 1984-03-21 | Recordati Chem Pharm | Diphenylalkylaminoalkyl esters |
-
1995
- 1995-07-14 IT ITMI951513A patent/IT1275532B/it active IP Right Grant
-
1996
- 1996-06-28 AT AT96924834T patent/ATE183644T1/de not_active IP Right Cessation
- 1996-06-28 JP JP9506222A patent/JPH11509214A/ja active Pending
- 1996-06-28 SK SK41-98A patent/SK4198A3/sk unknown
- 1996-06-28 DK DK96924834T patent/DK0839036T3/da active
- 1996-06-28 KR KR1019980700039A patent/KR19990028741A/ko not_active Application Discontinuation
- 1996-06-28 CZ CZ98116A patent/CZ11698A3/cs unknown
- 1996-06-28 IL IL12230296A patent/IL122302A/xx not_active IP Right Cessation
- 1996-06-28 HU HU9802736A patent/HUP9802736A3/hu unknown
- 1996-06-28 CN CN96195439A patent/CN1190345A/zh active Pending
- 1996-06-28 EP EP96924834A patent/EP0839036B1/de not_active Expired - Lifetime
- 1996-06-28 WO PCT/EP1996/002872 patent/WO1997003669A1/en not_active Application Discontinuation
- 1996-06-28 AU AU65164/96A patent/AU690471B2/en not_active Ceased
- 1996-06-28 ES ES96924834T patent/ES2138359T3/es not_active Expired - Lifetime
- 1996-06-28 CA CA002219501A patent/CA2219501A1/en not_active Abandoned
- 1996-06-28 DE DE69603968T patent/DE69603968T2/de not_active Expired - Fee Related
- 1996-07-12 ZA ZA965924A patent/ZA965924B/xx unknown
-
1998
- 1998-01-14 NO NO980171A patent/NO980171L/no not_active Application Discontinuation
-
1999
- 1999-08-26 GR GR990402179T patent/GR3031096T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL122302A0 (en) | 1998-04-05 |
| AU690471B2 (en) | 1998-04-23 |
| DE69603968D1 (de) | 1999-09-30 |
| ATE183644T1 (de) | 1999-09-15 |
| DK0839036T3 (da) | 2000-01-24 |
| ITMI951513A1 (it) | 1997-01-14 |
| HUP9802736A3 (en) | 2000-03-28 |
| KR19990028741A (ko) | 1999-04-15 |
| IT1275532B (it) | 1997-08-07 |
| IL122302A (en) | 2000-08-13 |
| EP0839036B1 (de) | 1999-08-25 |
| CZ11698A3 (cs) | 1998-06-17 |
| ZA965924B (en) | 1997-01-30 |
| WO1997003669A1 (en) | 1997-02-06 |
| GR3031096T3 (en) | 1999-12-31 |
| AU6516496A (en) | 1997-02-18 |
| ITMI951513A0 (it) | 1995-07-14 |
| JPH11509214A (ja) | 1999-08-17 |
| DE69603968T2 (de) | 2000-04-06 |
| NO980171D0 (no) | 1998-01-14 |
| NO980171L (no) | 1998-01-14 |
| CN1190345A (zh) | 1998-08-12 |
| ES2138359T3 (es) | 2000-01-01 |
| CA2219501A1 (en) | 1997-02-06 |
| HUP9802736A2 (hu) | 1999-03-29 |
| EP0839036A1 (de) | 1998-05-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5912351A (en) | Anhydrous 1,4-Dihydropyridines and salts thereof | |
| ES2206989T3 (es) | Compuestos de piridilo y composiciones farmaceuticas que los contienen. | |
| BG62002B1 (bg) | (-)-[[4-(1,4,5,6-тетрахидро-4-метил-6-оксо-3-пиридазинил)фенил]хидразоно]пропандинитрил | |
| TW200813012A (en) | New indications for direct thrombin inhibitors | |
| SK4198A3 (en) | Use of 1,4-dihydropyridine derivatives in the prevention and therapy of atherosclerotic degradation of arterial walls | |
| US5225420A (en) | Use of tetrahydrothienopyridine derivatives as angiogenesis inhibitors | |
| JP2009543844A (ja) | 直接トロンビン阻害剤の新しい小児適応症 | |
| US5696139A (en) | Use of S-enantiomers of 1,4-dihydropyridine derivatives for treating heart failure | |
| JPH03503525A (ja) | 腫瘍疾患治療用の光学的に純粋なｒ‐（‐）‐ニグルジピン及びその誘導体 | |
| JP4783152B2 (ja) | 血管内膜肥厚抑制薬 | |
| CN1129907A (zh) | (r)-氨氯地平对平滑肌细胞移行的抑制 | |
| WO1997009301A1 (fr) | Derives de 2-acylaminobenzamide, preventif et remede contre des maladies causees par une surmultiplication des cellules vasculaires de l'intima | |
| US5691339A (en) | Circulatory disorder improving agent | |
| US5530001A (en) | Pharmaceutical use of dihydropyridine derivative | |
| MXPA98000387A (en) | Use of 1,4-dihydropyridine derivatives in the prevention and atterosclerotic degradation therapy of artery walls | |
| EP1206936B1 (de) | Phenylessigsäure-Zusammensetzungen zur Behandlung oder Vorbeugung von Hypercholesterolemia | |
| KR100355973B1 (ko) | 페닐-치환1,4-디히드로피리딘 | |
| US20120022088A1 (en) | Pharmaceutical combination of 5-fluorouracil and derivate of 1,4-dihydropyridine and its use in the treatment of cancer | |
| NZ204283A (en) | Dihydropyridine derivatives and pharmaceutical compositions | |
| CN101691351B (zh) | 4-胺基丙烯基苯基-1,4-二氢吡啶类的合成及其药物用途 | |
| JPH02243679A (ja) | 腫瘍転移阻害剤 | |
| JPH09501923A (ja) | 薬剤としてのｎ−アルキル化された１，４−ジヒドロピリジンジカルボン酸エステル類の使用 | |
| KR20060125816A (ko) | 호중구증다 억제제 | |
| EP0825862A1 (de) | Verwendung von (s)-enantiomeren von 1,4-dihydropyridin-derivaten zur behandlung von herzversagen | |
| KR20050039700A (ko) | 이식거부 치료용 화합물 및 치료 방법 |