JP2007169284A - 洞房結節If電流阻害剤およびカルシウム阻害剤の新規な組み合わせならびにそれを含む医薬組成物 - Google Patents
洞房結節If電流阻害剤およびカルシウム阻害剤の新規な組み合わせならびにそれを含む医薬組成物 Download PDFInfo
- Publication number
- JP2007169284A JP2007169284A JP2006343824A JP2006343824A JP2007169284A JP 2007169284 A JP2007169284 A JP 2007169284A JP 2006343824 A JP2006343824 A JP 2006343824A JP 2006343824 A JP2006343824 A JP 2006343824A JP 2007169284 A JP2007169284 A JP 2007169284A
- Authority
- JP
- Japan
- Prior art keywords
- inhibitor
- combination
- calcium
- ivabradine
- pharmaceutical composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000480 calcium channel blocker Substances 0.000 title claims abstract description 27
- 239000003112 inhibitor Substances 0.000 title claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
- 210000001013 sinoatrial node Anatomy 0.000 title claims abstract description 15
- 229960003825 ivabradine Drugs 0.000 claims abstract description 26
- 229960000528 amlodipine Drugs 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 12
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 150000004677 hydrates Chemical class 0.000 claims description 13
- 125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 claims description 10
- HLUKNZUABFFNQS-ZMBIFBSDSA-N ivabradine hydrochloride Chemical group Cl.C1CC2=CC(OC)=C(OC)C=C2CC(=O)N1CCCN(C)C[C@H]1CC2=C1C=C(OC)C(OC)=C2 HLUKNZUABFFNQS-ZMBIFBSDSA-N 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 229960004005 amlodipine besylate Drugs 0.000 claims description 4
- 229960000504 ivabradine hydrochloride Drugs 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 239000004480 active ingredient Substances 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- ACRHBAYQBXXRTO-OAQYLSRUSA-N ivabradine Chemical compound C1CC2=CC(OC)=C(OC)C=C2CC(=O)N1CCCN(C)C[C@H]1CC2=C1C=C(OC)C(OC)=C2 ACRHBAYQBXXRTO-OAQYLSRUSA-N 0.000 abstract description 25
- 206010019233 Headaches Diseases 0.000 abstract description 4
- 231100000869 headache Toxicity 0.000 abstract description 4
- 210000003141 lower extremity Anatomy 0.000 abstract description 4
- 230000009977 dual effect Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000006872 improvement Effects 0.000 abstract description 2
- 206010030113 Oedema Diseases 0.000 abstract 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 abstract 1
- 230000002301 combined effect Effects 0.000 abstract 1
- 230000009931 harmful effect Effects 0.000 abstract 1
- 150000007513 acids Chemical class 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 208000014987 limb edema Diseases 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 230000033764 rhythmic process Effects 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 208000001871 Tachycardia Diseases 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000000314 lubricant 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
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000000304 vasodilatating effect Effects 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- KEDQCFRVSHYKLR-UHFFFAOYSA-N 3-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCN1C(=O)CC2=CC(OC)=C(OC)C=C2CC1 KEDQCFRVSHYKLR-UHFFFAOYSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 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 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 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-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 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
- 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
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000008272 agar Substances 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
- 210000000709 aorta Anatomy 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000008901 benefit Effects 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
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000002057 chronotropic effect Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940127292 dihydropyridine calcium channel blocker Drugs 0.000 description 1
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 229960001021 lactose monohydrate Drugs 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- -1 troches Substances 0.000 description 1
- 229950003419 zatebradine Drugs 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
- 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
-
- 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
-
- 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
-
- 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
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
【解決手段】イバブラジンのような洞房結節If電流阻害剤と、アムロジピンのようなカルシウム阻害剤とを組み合わせることによって、カルシウム阻害剤の効果を増強できるだけではなく、心臓への有害作用である下肢の浮腫及び頭痛等の改善を伴う二重効果が示され、より安全性の高いアンギナの処置に使用が可能になる等の有益な併用効果を有することを見出した。
【選択図】なし
Description
・ 希釈剤として:乳糖、デキストロース、スクロース、マンニトール、ソルビトール、セルロース、グリセロール、
・ 滑沢剤として:シリカ、タルク、ステアリン酸ならびにそのマグネシウム塩およびカルシウム塩、ポリエチレングリコール、
・ 結合剤として:ケイ酸アルミニウムおよびケイ酸マグネシウム、デンプン、ゼラチン、トラガカント、メチルセルロース、カルボキシメチルセルロースナトリウムおよびポリビニルピロリドン、
・ 崩壊剤として:寒天、アルギン酸およびそのナトリウム塩、発泡性混合物。
それぞれイバブラジン10mgおよびアムロジピン5mgを含む錠剤1000個についての調製処方:
イバブラジン塩酸塩 10g
ベシル酸アムロジピン 5g
乳糖一水和物 62g
ステアリン酸マグネシウム 1.3g
ポビドン 9g
無水コロイドシリカ 0.3g
セルロースグリコール酸ナトリウム 30g
ステアリン酸 2.6g
実施例1
・ ジヒドロピリジン系カルシウムアンタゴニストで処置されており、(カルシウムアンタゴニストにかかわらず)苦痛のある狭心症発作を依然として訴える患者で実施された二つの臨床試験は、イバブラジンとの同時処置がこれらの発作を大いに実質的に(約60%)低減できることを示した。
組み入れ時およびイバブラジンを1年間投与されたときの、ジヒドロピリジンを投与されている患者における狭心症発作回数の変化
100患者年の曝露あたりのアムロジピン単独またはアムロジピン+イバブラジンの組み合わせで処置された冠状動脈患者における有害事象
Claims (12)
- 選択的かつ特異的な洞房結節If電流阻害剤およびカルシウム阻害剤の組み合わせ。
- 選択的かつ特異的な洞房結節If電流阻害剤が、イバブラジン、すなわち3−{3−[{[(7S)−3,4−ジメトキシビシクロ[4.2.0]オクタ−1,3,5−トリエン−7−イル]メチル}(メチル)アミノ]プロピル}−7,8−ジメトキシ−1,3,4,5−テトラヒドロ−2H−3−ベンゾアゼピン−2−オン、またはその水和物、結晶形態、もしくは薬学的に許容される酸との付加塩のうちの一つである、請求項1記載の組み合わせ。
- 選択的かつ特異的な洞房結節If電流阻害剤が、イバブラジン、すなわち3−{3−[{[(7S)−3,4−ジメトキシビシクロ[4.2.0]オクタ−1,3,5−トリエン−7−イル]メチル}(メチル)アミノ]プロピル}−7,8−ジメトキシ−1,3,4,5−テトラヒドロ−2H−3−ベンゾアゼピン−2−オンの塩酸塩、またはその水和物もしくは結晶形態のうちの一つである、請求項1記載の組み合わせ。
- カルシウム阻害剤が、ジヒドロピリジンクラスに属する、請求項1記載の組み合わせ。
- カルシウム阻害剤が、アムロジピン、またはその水和物、結晶形態もしくは薬学的に許容される酸との付加塩のうちの一つである、請求項1記載の組み合わせ。
- カルシウム阻害剤が、ベシル酸アムロジピンまたはその水和物もしくは結晶形態のうちの一つである、請求項1記載の組み合わせ。
- イバブラジン、またはその水和物、結晶形態もしくは薬学的に許容される酸との付加塩のうちの一つと、アムロジピン、またはその水和物、結晶形態もしくは薬学的に許容される酸との付加塩のうちの一つとを含む、請求項1記載の組み合わせ。
- イバブラジン塩酸塩、またはその水和物もしくは結晶形態のうちの一つと、ベシル酸アムロジピン、またはその水和物もしくは結晶形態のうちの一つとを含む、請求項1記載の組み合わせ。
- 有効成分として、請求項1から8のいずれか一項記載の、カルシウム阻害剤と組み合わせた選択的かつ特異的な洞房結節If電流阻害剤を、それだけで、または一つ以上の薬学的に許容される賦形剤と組み合わせて含む医薬組成物。
- 有効成分として、ベシル酸アムロジピン、またはその水和物もしくは結晶形態のうちの一つと組み合わせたイバブラジン塩酸塩、またはその水和物もしくは結晶形態のうちの一つを、それだけで、または一つ以上の薬学的に許容される賦形剤と組み合わせて含む、請求項9記載の医薬組成物。
- アンギナの処置のための医薬の製造に使用するための、請求項9および10のいずれか一項記載の医薬組成物。
- アンギナの処置用の医薬組成物を得ることにおける、請求項1から8のいずれか一項記載の組み合わせの使用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0513008 | 2005-12-21 | ||
FR0513008A FR2894826B1 (fr) | 2005-12-21 | 2005-12-21 | Nouvelle association d'un inhibiteur du courant if sinusal et d'un inhibiteur calcique et les compositions pharmaceutiques qui la contiennent |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010263499A Division JP2011068661A (ja) | 2005-12-21 | 2010-11-26 | 洞房結節If電流阻害剤およびカルシウム阻害剤の新規な組み合わせならびにそれを含む医薬組成物 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2007169284A true JP2007169284A (ja) | 2007-07-05 |
JP4783275B2 JP4783275B2 (ja) | 2011-09-28 |
Family
ID=37075950
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006343824A Active JP4783275B2 (ja) | 2005-12-21 | 2006-12-21 | 洞房結節If電流阻害剤およびカルシウム阻害剤の新規な組み合わせならびにそれを含む医薬組成物 |
JP2010263499A Pending JP2011068661A (ja) | 2005-12-21 | 2010-11-26 | 洞房結節If電流阻害剤およびカルシウム阻害剤の新規な組み合わせならびにそれを含む医薬組成物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010263499A Pending JP2011068661A (ja) | 2005-12-21 | 2010-11-26 | 洞房結節If電流阻害剤およびカルシウム阻害剤の新規な組み合わせならびにそれを含む医薬組成物 |
Country Status (41)
Country | Link |
---|---|
US (3) | US20070142356A1 (ja) |
EP (1) | EP1800683B1 (ja) |
JP (2) | JP4783275B2 (ja) |
KR (1) | KR100907584B1 (ja) |
CN (1) | CN101015556B (ja) |
AP (1) | AP2208A (ja) |
AR (1) | AR058575A1 (ja) |
AT (1) | ATE488239T1 (ja) |
AU (1) | AU2006252211B2 (ja) |
BR (1) | BRPI0605516A (ja) |
CA (1) | CA2571649C (ja) |
CO (1) | CO5790167A1 (ja) |
CR (1) | CR8813A (ja) |
CY (1) | CY1111007T1 (ja) |
DE (1) | DE602006018247D1 (ja) |
DK (1) | DK1800683T3 (ja) |
EA (1) | EA013536B1 (ja) |
ES (1) | ES2356660T3 (ja) |
FR (1) | FR2894826B1 (ja) |
GE (1) | GEP20094603B (ja) |
GT (1) | GT200600523A (ja) |
HK (1) | HK1106442A1 (ja) |
HR (1) | HRP20110028T1 (ja) |
IL (1) | IL180209A (ja) |
JO (1) | JO2675B1 (ja) |
MA (1) | MA28724B1 (ja) |
MX (1) | MXPA06014884A (ja) |
MY (1) | MY143563A (ja) |
NO (1) | NO337509B1 (ja) |
NZ (1) | NZ552222A (ja) |
PE (1) | PE20071133A1 (ja) |
PL (1) | PL1800683T3 (ja) |
PT (1) | PT1800683E (ja) |
RS (1) | RS51534B (ja) |
SA (1) | SA06270482B1 (ja) |
SG (1) | SG133546A1 (ja) |
SI (1) | SI1800683T1 (ja) |
TW (1) | TWI373344B (ja) |
UA (1) | UA91507C2 (ja) |
WO (1) | WO2007077329A2 (ja) |
ZA (1) | ZA200610822B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009191069A (ja) * | 2008-02-14 | 2009-08-27 | Lab Servier | 洞房結節If電流阻害剤とβブロッカーとの組み合わせ |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2894826B1 (fr) * | 2005-12-21 | 2010-10-22 | Servier Lab | Nouvelle association d'un inhibiteur du courant if sinusal et d'un inhibiteur calcique et les compositions pharmaceutiques qui la contiennent |
FR2920773B1 (fr) | 2007-09-11 | 2009-10-23 | Servier Lab | Derives de 1,2,4,5-tetrahydro-3h-benzazepines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
CN101564394B (zh) * | 2008-04-21 | 2010-12-15 | 鲁南制药集团股份有限公司 | 含有伊伐布雷定和曲美他嗪的药物组合物 |
WO2009158005A1 (en) * | 2008-06-27 | 2009-12-30 | Concert Pharmaceuticals, Inc. | Benzazepinone compounds |
FR2938194B1 (fr) * | 2008-11-07 | 2012-08-31 | Servier Lab | Utilisation de l'ivabradine comme agent de diagnostic dans la methode d'angiographie coronaire par tomodensitometrie multicoupe |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS62240660A (ja) * | 1986-04-04 | 1987-10-21 | フアイザ−・リミテツド | アムロジピンのベンゼンスルホン酸塩 |
JP2005298480A (ja) * | 2004-04-13 | 2005-10-27 | Lab Servier | イバブラジン及び薬学的に許容し得る酸とのその付加塩の新規合成方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2681862B1 (fr) * | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
US20030092745A1 (en) * | 2000-02-25 | 2003-05-15 | Pfizer Inc. | Combination therapy |
JP4194095B2 (ja) * | 2001-09-11 | 2008-12-10 | 旭化成ファーマ株式会社 | 脳血管障害、心疾患の予防・治療用医薬組成物 |
US6828339B2 (en) * | 2001-11-21 | 2004-12-07 | Synthon Bv | Amlodipine salt forms and processes for preparing them |
FR2894826B1 (fr) * | 2005-12-21 | 2010-10-22 | Servier Lab | Nouvelle association d'un inhibiteur du courant if sinusal et d'un inhibiteur calcique et les compositions pharmaceutiques qui la contiennent |
-
2005
- 2005-12-21 FR FR0513008A patent/FR2894826B1/fr not_active Expired - Fee Related
-
2006
- 2006-12-14 CR CR8813A patent/CR8813A/es not_active Application Discontinuation
- 2006-12-15 MA MA29539A patent/MA28724B1/fr unknown
- 2006-12-18 AP AP2006003858A patent/AP2208A/xx active
- 2006-12-18 PE PE2006001618A patent/PE20071133A1/es active IP Right Grant
- 2006-12-18 MX MXPA06014884A patent/MXPA06014884A/es active IP Right Grant
- 2006-12-18 SG SG200608806-6A patent/SG133546A1/en unknown
- 2006-12-19 NO NO20065903A patent/NO337509B1/no not_active IP Right Cessation
- 2006-12-20 PT PT06291991T patent/PT1800683E/pt unknown
- 2006-12-20 PL PL06291991T patent/PL1800683T3/pl unknown
- 2006-12-20 AT AT06291991T patent/ATE488239T1/de active
- 2006-12-20 SA SA06270482A patent/SA06270482B1/ar unknown
- 2006-12-20 ES ES06291991T patent/ES2356660T3/es active Active
- 2006-12-20 RS RSP-2010/0554A patent/RS51534B/en unknown
- 2006-12-20 DK DK06291991.5T patent/DK1800683T3/da active
- 2006-12-20 EA EA200602156A patent/EA013536B1/ru unknown
- 2006-12-20 GE GEAP20069773A patent/GEP20094603B/en unknown
- 2006-12-20 SI SI200630854T patent/SI1800683T1/sl unknown
- 2006-12-20 GT GT200600523A patent/GT200600523A/es unknown
- 2006-12-20 IL IL180209A patent/IL180209A/en active IP Right Grant
- 2006-12-20 CO CO06127373A patent/CO5790167A1/es not_active Application Discontinuation
- 2006-12-20 MY MYPI20064723A patent/MY143563A/en unknown
- 2006-12-20 NZ NZ552222A patent/NZ552222A/en not_active IP Right Cessation
- 2006-12-20 WO PCT/FR2006/002805 patent/WO2007077329A2/fr active Application Filing
- 2006-12-20 TW TW095148015A patent/TWI373344B/zh not_active IP Right Cessation
- 2006-12-20 EP EP06291991A patent/EP1800683B1/fr active Active
- 2006-12-20 AR ARP060105640A patent/AR058575A1/es not_active Application Discontinuation
- 2006-12-20 UA UAA200613551A patent/UA91507C2/ru unknown
- 2006-12-20 DE DE602006018247T patent/DE602006018247D1/de active Active
- 2006-12-21 KR KR1020060131725A patent/KR100907584B1/ko active IP Right Grant
- 2006-12-21 JO JO2006490A patent/JO2675B1/en active
- 2006-12-21 BR BRPI0605516-8A patent/BRPI0605516A/pt not_active Application Discontinuation
- 2006-12-21 CA CA2571649A patent/CA2571649C/fr active Active
- 2006-12-21 AU AU2006252211A patent/AU2006252211B2/en not_active Ceased
- 2006-12-21 ZA ZA200610822A patent/ZA200610822B/xx unknown
- 2006-12-21 JP JP2006343824A patent/JP4783275B2/ja active Active
- 2006-12-21 CN CN2006100643177A patent/CN101015556B/zh not_active Expired - Fee Related
- 2006-12-21 US US11/643,046 patent/US20070142356A1/en not_active Abandoned
-
2007
- 2007-11-05 HK HK07111993.7A patent/HK1106442A1/xx not_active IP Right Cessation
-
2009
- 2009-04-22 US US12/386,687 patent/US20090215745A1/en not_active Abandoned
-
2010
- 2010-11-26 JP JP2010263499A patent/JP2011068661A/ja active Pending
- 2010-11-29 CY CY20101101086T patent/CY1111007T1/el unknown
-
2011
- 2011-01-17 HR HR20110028T patent/HRP20110028T1/hr unknown
- 2011-05-13 US US13/068,551 patent/US20110230466A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS62240660A (ja) * | 1986-04-04 | 1987-10-21 | フアイザ−・リミテツド | アムロジピンのベンゼンスルホン酸塩 |
JP2005298480A (ja) * | 2004-04-13 | 2005-10-27 | Lab Servier | イバブラジン及び薬学的に許容し得る酸とのその付加塩の新規合成方法 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009191069A (ja) * | 2008-02-14 | 2009-08-27 | Lab Servier | 洞房結節If電流阻害剤とβブロッカーとの組み合わせ |
JP2012211179A (ja) * | 2008-02-14 | 2012-11-01 | Lab Servier | 洞房結節If電流阻害剤とβブロッカーとの組み合わせ |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4783275B2 (ja) | 洞房結節If電流阻害剤およびカルシウム阻害剤の新規な組み合わせならびにそれを含む医薬組成物 | |
JP5480202B2 (ja) | 心不全の処置における洞房結節If電流阻害剤およびアンギオテンシン変換酵素阻害剤の組み合わせの使用 | |
JP4705564B2 (ja) | 洞房結節If電流阻害剤およびアンギオテンシン変換酵素阻害剤の新規な組み合わせならびにそれを含む医薬組成物 | |
JP4874482B2 (ja) | アスピリンを含有する医薬組成物 | |
JP2012211179A (ja) | 洞房結節If電流阻害剤とβブロッカーとの組み合わせ | |
JP5395998B2 (ja) | アゴメラチンとノルアドレナリン再取り込み阻害剤との新たな組み合わせ、及びそれを含有している医薬組成物 | |
WO2011137601A1 (zh) | 左旋氨氯地平复方药物制剂 | |
WO2011141888A1 (en) | Use of dronedarone for the preparation of a medicament for the prevention of cardiovacular hospitalizations or death or cardiovascular events in patients with permanent atrial fibrillation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100323 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100617 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100727 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101126 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20101129 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20110203 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110329 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110510 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20110705 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110708 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140715 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4783275 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |