JP5288678B2 - レニンインヒビター、カルシウムチャネルブロッカーおよび利尿薬を含む医薬組成物 - Google Patents
レニンインヒビター、カルシウムチャネルブロッカーおよび利尿薬を含む医薬組成物 Download PDFInfo
- Publication number
- JP5288678B2 JP5288678B2 JP2004505094A JP2004505094A JP5288678B2 JP 5288678 B2 JP5288678 B2 JP 5288678B2 JP 2004505094 A JP2004505094 A JP 2004505094A JP 2004505094 A JP2004505094 A JP 2004505094A JP 5288678 B2 JP5288678 B2 JP 5288678B2
- Authority
- JP
- Japan
- Prior art keywords
- aliskiren
- pharmaceutical composition
- diabetic
- amlodipine
- renal
- 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.)
- Expired - Fee Related
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 26
- 239000002461 renin inhibitor Substances 0.000 title abstract description 22
- 229940086526 renin-inhibitors Drugs 0.000 title abstract description 22
- 229940127291 Calcium channel antagonist Drugs 0.000 title abstract description 18
- 239000000480 calcium channel blocker Substances 0.000 title abstract description 18
- 239000002934 diuretic Substances 0.000 title abstract description 14
- 230000001882 diuretic effect Effects 0.000 title abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 35
- 206010020772 Hypertension Diseases 0.000 claims abstract description 20
- UXOWGYHJODZGMF-QORCZRPOSA-N Aliskiren Chemical compound COCCCOC1=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=CC=C1OC UXOWGYHJODZGMF-QORCZRPOSA-N 0.000 claims description 43
- 229960004601 aliskiren Drugs 0.000 claims description 43
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 claims description 36
- 229960002003 hydrochlorothiazide Drugs 0.000 claims description 35
- 229960000528 amlodipine Drugs 0.000 claims description 32
- 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 claims description 32
- 150000003839 salts Chemical group 0.000 claims description 26
- 239000004480 active ingredient Substances 0.000 claims description 10
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 15
- 206010019280 Heart failures Diseases 0.000 abstract description 14
- 201000010099 disease Diseases 0.000 abstract description 14
- 238000000034 method Methods 0.000 abstract description 13
- 230000001684 chronic effect Effects 0.000 abstract description 11
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 9
- 208000001647 Renal Insufficiency Diseases 0.000 abstract description 9
- 201000006370 kidney failure Diseases 0.000 abstract description 9
- 230000001154 acute effect Effects 0.000 abstract description 8
- 201000002793 renal fibrosis Diseases 0.000 abstract description 7
- 206010007559 Cardiac failure congestive Diseases 0.000 abstract description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 abstract description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 abstract description 6
- 210000002744 extracellular matrix Anatomy 0.000 abstract description 6
- 210000000329 smooth muscle myocyte Anatomy 0.000 abstract description 6
- 208000019553 vascular disease Diseases 0.000 abstract description 6
- 208000007342 Diabetic Nephropathies Diseases 0.000 abstract description 5
- 208000006011 Stroke Diseases 0.000 abstract description 5
- 208000033679 diabetic kidney disease Diseases 0.000 abstract description 5
- 201000001320 Atherosclerosis Diseases 0.000 abstract description 4
- 206010003658 Atrial Fibrillation Diseases 0.000 abstract description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 abstract description 4
- 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 abstract description 4
- 208000010412 Glaucoma Diseases 0.000 abstract description 4
- 206010018364 Glomerulonephritis Diseases 0.000 abstract description 4
- 208000010159 IgA glomerulonephritis Diseases 0.000 abstract description 4
- 206010021263 IgA nephropathy Diseases 0.000 abstract description 4
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 abstract description 4
- 208000019695 Migraine disease Diseases 0.000 abstract description 4
- 208000018262 Peripheral vascular disease Diseases 0.000 abstract description 4
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 abstract description 4
- 208000003782 Raynaud disease Diseases 0.000 abstract description 4
- 208000012322 Raynaud phenomenon Diseases 0.000 abstract description 4
- 206010039710 Scleroderma Diseases 0.000 abstract description 4
- 206010039808 Secondary aldosteronism Diseases 0.000 abstract description 4
- 206010042600 Supraventricular arrhythmias Diseases 0.000 abstract description 4
- 206010047281 Ventricular arrhythmia Diseases 0.000 abstract description 4
- 238000009825 accumulation Methods 0.000 abstract description 4
- 208000010877 cognitive disease Diseases 0.000 abstract description 4
- 206010061989 glomerulosclerosis Diseases 0.000 abstract description 4
- 206010020718 hyperplasia Diseases 0.000 abstract description 4
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 abstract description 4
- 206010027599 migraine Diseases 0.000 abstract description 4
- 208000010125 myocardial infarction Diseases 0.000 abstract description 4
- 201000008312 primary pulmonary hypertension Diseases 0.000 abstract description 4
- 230000002062 proliferating effect Effects 0.000 abstract description 4
- 201000001474 proteinuria Diseases 0.000 abstract description 4
- 208000005069 pulmonary fibrosis Diseases 0.000 abstract description 4
- 208000037812 secondary pulmonary hypertension Diseases 0.000 abstract description 4
- 206010003662 Atrial flutter Diseases 0.000 abstract description 3
- 241000124008 Mammalia Species 0.000 abstract description 3
- 208000032594 Vascular Remodeling Diseases 0.000 abstract description 3
- 208000017169 kidney disease Diseases 0.000 abstract description 3
- 230000002792 vascular Effects 0.000 abstract description 3
- 206010046798 Uterine leiomyoma Diseases 0.000 abstract description 2
- 201000010260 leiomyoma Diseases 0.000 abstract description 2
- 206010019668 Hepatic fibrosis Diseases 0.000 abstract 1
- 208000021642 Muscular disease Diseases 0.000 abstract 1
- 201000009623 Myopathy Diseases 0.000 abstract 1
- 230000000747 cardiac effect Effects 0.000 abstract 1
- 230000001627 detrimental effect Effects 0.000 abstract 1
- 230000003176 fibrotic effect Effects 0.000 abstract 1
- 230000002685 pulmonary effect Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 26
- 229940079593 drug Drugs 0.000 description 25
- 241000700159 Rattus Species 0.000 description 20
- 238000012360 testing method Methods 0.000 description 16
- 230000036454 renin-angiotensin system Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 13
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 13
- VPGRYOFKCNULNK-ACXQXYJUSA-N Deoxycorticosterone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)C)[C@@]1(C)CC2 VPGRYOFKCNULNK-ACXQXYJUSA-N 0.000 description 11
- 230000009471 action Effects 0.000 description 11
- 230000036772 blood pressure Effects 0.000 description 11
- 238000002648 combination therapy Methods 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- 210000003734 kidney Anatomy 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 10
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 9
- 230000003276 anti-hypertensive effect Effects 0.000 description 9
- 239000005541 ACE inhibitor Substances 0.000 description 8
- 102400000345 Angiotensin-2 Human genes 0.000 description 8
- 101800000733 Angiotensin-2 Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 229950006323 angiotensin ii Drugs 0.000 description 8
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 101150059573 AGTR1 gene Proteins 0.000 description 7
- 238000010998 test method Methods 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 6
- 239000003651 drinking water Substances 0.000 description 6
- 235000020188 drinking water Nutrition 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 238000009097 single-agent therapy Methods 0.000 description 5
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 4
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 4
- 230000031018 biological processes and functions Effects 0.000 description 4
- 229940109239 creatinine Drugs 0.000 description 4
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 230000004761 fibrosis Effects 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- 102400000344 Angiotensin-1 Human genes 0.000 description 3
- 101800000734 Angiotensin-1 Proteins 0.000 description 3
- 102000004881 Angiotensinogen Human genes 0.000 description 3
- 108090001067 Angiotensinogen Proteins 0.000 description 3
- 101800004538 Bradykinin Proteins 0.000 description 3
- 102400000967 Bradykinin Human genes 0.000 description 3
- 208000032781 Diabetic cardiomyopathy Diseases 0.000 description 3
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108090000783 Renin Proteins 0.000 description 3
- 201000003099 Renovascular Hypertension Diseases 0.000 description 3
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 3
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 3
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 3
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 3
- 230000004872 arterial blood pressure Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 3
- 210000001105 femoral artery Anatomy 0.000 description 3
- -1 galopamil Chemical compound 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 230000001631 hypertensive effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 2
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 2
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 2
- 206010048554 Endothelial dysfunction Diseases 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- 229920000153 Povidone-iodine Polymers 0.000 description 2
- 102100028255 Renin Human genes 0.000 description 2
- 208000004608 Ureteral Obstruction Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 229960002478 aldosterone Drugs 0.000 description 2
- 229960002576 amiloride Drugs 0.000 description 2
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 2
- 210000000702 aorta abdominal Anatomy 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000009530 blood pressure measurement Methods 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000001447 compensatory effect Effects 0.000 description 2
- 229960004486 desoxycorticosterone acetate Drugs 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000008694 endothelial dysfunction Effects 0.000 description 2
- 230000008753 endothelial function Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 230000001434 glomerular Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 210000005240 left ventricle Anatomy 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229960001621 povidone-iodine Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 210000002254 renal artery Anatomy 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 208000037999 tubulointerstitial fibrosis Diseases 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 210000000626 ureter Anatomy 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 230000004218 vascular function Effects 0.000 description 2
- 230000002227 vasoactive effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UXOWGYHJODZGMF-IYQSZBERSA-N (2s)-5-amino-n-(3-amino-2,2-dimethyl-3-oxopropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-2-propan-2-ylnonanamide Chemical compound COCCCOC1=CC(CC(CC(N)C(O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=CC=C1OC UXOWGYHJODZGMF-IYQSZBERSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- NMKSAYKQLCHXDK-UHFFFAOYSA-N 3,3-diphenyl-N-(1-phenylethyl)-1-propanamine Chemical compound C=1C=CC=CC=1C(C)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 NMKSAYKQLCHXDK-UHFFFAOYSA-N 0.000 description 1
- 101150116411 AGTR2 gene Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- 206010005746 Blood pressure fluctuation Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010021036 Hyponatraemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- HBNPJJILLOYFJU-VMPREFPWSA-N Mibefradil Chemical compound C1CC2=CC(F)=CC=C2[C@H](C(C)C)[C@@]1(OC(=O)COC)CCN(C)CCCC1=NC2=CC=CC=C2N1 HBNPJJILLOYFJU-VMPREFPWSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 201000004458 Myoma Diseases 0.000 description 1
- 208000013901 Nephropathies and tubular disease Diseases 0.000 description 1
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 201000004239 Secondary hypertension Diseases 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 206010042957 Systolic hypertension Diseases 0.000 description 1
- FNYLWPVRPXGIIP-UHFFFAOYSA-N Triamterene Chemical compound NC1=NC2=NC(N)=NC(N)=C2N=C1C1=CC=CC=C1 FNYLWPVRPXGIIP-UHFFFAOYSA-N 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960001301 amobarbital Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001396 anti-anti-diuretic effect Effects 0.000 description 1
- 230000001598 anti-natriuretic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000417 anti-transforming effect Effects 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000001008 atrial appendage Anatomy 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229960004064 bumetanide Drugs 0.000 description 1
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229960002155 chlorothiazide Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- AVOLMBLBETYQHX-UHFFFAOYSA-N etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 description 1
- 229960003199 etacrynic acid Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 229960002602 fendiline Drugs 0.000 description 1
- SMANXXCATUTDDT-QPJJXVBHSA-N flunarizine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCN(C\C=C\C=2C=CC=CC=2)CC1 SMANXXCATUTDDT-QPJJXVBHSA-N 0.000 description 1
- 229960000326 flunarizine Drugs 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000023560 heart growth Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- CZRQXSDBMCMPNJ-ZUIPZQNBSA-N lisinopril dihydrate Chemical compound O.O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 CZRQXSDBMCMPNJ-ZUIPZQNBSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 1
- AQCHWTWZEMGIFD-UHFFFAOYSA-N metolazone Chemical compound CC1NC2=CC(Cl)=C(S(N)(=O)=O)C=C2C(=O)N1C1=CC=CC=C1C AQCHWTWZEMGIFD-UHFFFAOYSA-N 0.000 description 1
- 229960002817 metolazone Drugs 0.000 description 1
- 229960004438 mibefradil Drugs 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000013059 nephrectomy Methods 0.000 description 1
- 210000000885 nephron Anatomy 0.000 description 1
- 229960005366 nilvadipine Drugs 0.000 description 1
- 229960000227 nisoldipine Drugs 0.000 description 1
- 229960005425 nitrendipine Drugs 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 230000004978 positive regulation of smooth muscle cell proliferation Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002796 renal vein Anatomy 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 238000011012 sanitization Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229960002909 spirapril Drugs 0.000 description 1
- 108700035424 spirapril Proteins 0.000 description 1
- HRWCVUIFMSZDJS-SZMVWBNQSA-N spirapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)CC1=CC=CC=C1 HRWCVUIFMSZDJS-SZMVWBNQSA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 210000003699 striated muscle Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008700 sympathetic activation Effects 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 229960001288 triamterene Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 230000003442 weekly effect Effects 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Reproductive Health (AREA)
- Vascular Medicine (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)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38154602P | 2002-05-17 | 2002-05-17 | |
| US60/381,546 | 2002-05-17 | ||
| PCT/EP2003/005188 WO2003097098A1 (en) | 2002-05-17 | 2003-05-16 | Pharmaceutical composition comprising a renin inhibitor, a calcium channel blocker and a diuretic |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010181380A Division JP2010280708A (ja) | 2002-05-17 | 2010-08-13 | レニンインヒビター、カルシウムチャネルブロッカーおよび利尿薬を含む医薬組成物 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005526850A JP2005526850A (ja) | 2005-09-08 |
| JP2005526850A5 JP2005526850A5 (enExample) | 2010-04-22 |
| JP5288678B2 true JP5288678B2 (ja) | 2013-09-11 |
Family
ID=29550141
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004505094A Expired - Fee Related JP5288678B2 (ja) | 2002-05-17 | 2003-05-16 | レニンインヒビター、カルシウムチャネルブロッカーおよび利尿薬を含む医薬組成物 |
| JP2010181380A Withdrawn JP2010280708A (ja) | 2002-05-17 | 2010-08-13 | レニンインヒビター、カルシウムチャネルブロッカーおよび利尿薬を含む医薬組成物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010181380A Withdrawn JP2010280708A (ja) | 2002-05-17 | 2010-08-13 | レニンインヒビター、カルシウムチャネルブロッカーおよび利尿薬を含む医薬組成物 |
Country Status (24)
| Country | Link |
|---|---|
| US (3) | US20050182042A1 (enExample) |
| EP (2) | EP1507558B8 (enExample) |
| JP (2) | JP5288678B2 (enExample) |
| KR (3) | KR20130109244A (enExample) |
| CN (1) | CN1655819A (enExample) |
| AT (1) | ATE520417T1 (enExample) |
| AU (1) | AU2003240669B2 (enExample) |
| BR (1) | BR0310084A (enExample) |
| CA (1) | CA2485081C (enExample) |
| CY (2) | CY1112013T1 (enExample) |
| DK (1) | DK1507558T3 (enExample) |
| EC (1) | ECSP045428A (enExample) |
| ES (1) | ES2369216T3 (enExample) |
| IL (1) | IL164837A (enExample) |
| LU (1) | LU92000I2 (enExample) |
| MX (1) | MXPA04011383A (enExample) |
| NO (1) | NO334382B1 (enExample) |
| NZ (1) | NZ536555A (enExample) |
| PL (1) | PL219032B1 (enExample) |
| PT (1) | PT1507558E (enExample) |
| RU (1) | RU2316318C2 (enExample) |
| SI (1) | SI1507558T1 (enExample) |
| WO (1) | WO2003097098A1 (enExample) |
| ZA (1) | ZA200408442B (enExample) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| US8168616B1 (en) * | 2000-11-17 | 2012-05-01 | Novartis Ag | Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension |
| ES2369216T3 (es) * | 2002-05-17 | 2011-11-28 | Novartis Pharma Ag | Composición farmacéutica que comprende un inhibidor de renina, un bloqueador del canal de calcio y un diurético. |
| CN100444840C (zh) | 2003-05-15 | 2008-12-24 | 罗斯坎普研究有限公司 | 减少淀粉样沉积、淀粉样神经毒性和小胶质增生的药物 |
| WO2005077418A1 (en) * | 2004-02-17 | 2005-08-25 | Novartis Ag | Combination of renin inhibitor and diuretics |
| MY148773A (en) * | 2004-03-17 | 2013-05-31 | Novartis Ag | Galenic formulations of organic compounds |
| WO2005089731A2 (en) * | 2004-03-17 | 2005-09-29 | Novartis Ag | Use of renin inhibitors in therapy |
| ES2257152B1 (es) * | 2004-05-31 | 2007-07-01 | Laboratorios Almirall S.A. | Combinaciones que comprenden agentes antimuscarinicos y agonistas beta-adrenergicos. |
| AU2005247105B2 (en) * | 2004-05-31 | 2010-11-11 | Laboratorios Almirall, S.A. | Combinations comprising antimuscarinic agents and corticosteroids |
| MY146830A (en) * | 2005-02-11 | 2012-09-28 | Novartis Ag | Combination of organic compounds |
| AU2006227283B2 (en) * | 2005-03-22 | 2010-07-01 | Novartis Ag | Biomarkers for efficacy of aliskiren as a hypertensive agent |
| WO2007056324A2 (en) * | 2005-11-08 | 2007-05-18 | Novartis Ag | Combination of an angiotensin ii receptor blocker, a calcium channel blocker and another active agent |
| AR057882A1 (es) | 2005-11-09 | 2007-12-26 | Novartis Ag | Compuestos de accion doble de bloqueadores del receptor de angiotensina e inhibidores de endopeptidasa neutra |
| GB0612540D0 (en) * | 2006-06-23 | 2006-08-02 | Novartis Ag | Galenical formulations of organic compounds |
| EP1891937A1 (en) * | 2006-08-25 | 2008-02-27 | Novartis AG | Galenic formulations of aliskiren |
| CA2668828A1 (en) * | 2006-11-07 | 2008-05-29 | Novartis Ag | Crystalline forms of aliskiren hemifumarate |
| RU2456267C2 (ru) * | 2006-11-09 | 2012-07-20 | Новартис Аг | Соль алискирена и оротовой кислоты |
| US8247370B2 (en) * | 2006-12-04 | 2012-08-21 | Promedior, Inc. | Conjoint therapy for treating fibrotic diseases |
| JP2010518147A (ja) * | 2007-02-16 | 2010-05-27 | ノバルティス アーゲー | 有機化合物の使用 |
| EP1972335A1 (en) * | 2007-03-23 | 2008-09-24 | Krka | Solid dosage forms comprising aliskiren and pharmaceutically acceptable salts thereof |
| RU2363472C2 (ru) * | 2007-05-22 | 2009-08-10 | Государственное образовательное учреждение высшего профессионального образования "Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова Федерального агентства по здравоохранению и социальному развитию" | Способ профилактики и лечения кардиоваскулярных осложнений у больных с хронической болезнью почек, находящихся на гемодиализе, имеющих анурию |
| US8497243B2 (en) * | 2007-07-06 | 2013-07-30 | Promedior, Inc. | Methods and compositions useful in the treatment of mucositis |
| US9884899B2 (en) | 2007-07-06 | 2018-02-06 | Promedior, Inc. | Methods for treating fibrosis using CRP antagonists |
| BRPI0817516A2 (pt) | 2007-10-05 | 2015-06-16 | Alzheimer S Inst Of America Inc | Método para reduzir deposição de amilóide, neurotoxicidade de amilóide e microgliose com o enantiômero de (-)-nilvadipino |
| EP2062874B1 (en) | 2007-11-20 | 2014-12-17 | KRKA, tovarna zdravil, d.d., Novo mesto | Process and intermediates for the preparation of aliskiren |
| EP2100599A1 (en) | 2008-03-13 | 2009-09-16 | Laboratorios Almirall, S.A. | Inhalation composition containing aclidinium for treatment of asthma and chronic obstructive pulmonary disease |
| RU2372079C1 (ru) * | 2008-05-20 | 2009-11-10 | Илья Николаевич Медведев | Способ коррекции уровня микровезикул в крови при артериальной гипертонии, дислипидемии и нарушении толерантности к глюкозе |
| RU2373932C1 (ru) * | 2008-05-20 | 2009-11-27 | Илья Николаевич Медведев | Способ коррекции уровня микровезикул в крови при артериальной гипертонии |
| JO3239B1 (ar) * | 2008-09-22 | 2018-03-08 | Novartis Ag | تركيبات جالينية من مركبات عضوية |
| RU2382644C1 (ru) * | 2008-11-05 | 2010-02-27 | Государственное образовательное учреждение высшего профессионального образования "Пермская государственная медицинская академия имени академика Е.А. Вагнера Федерального агентства по здравоохранению и социальному развитию" | Способ коррекции гипертрофии левого желудочка у больных ибс в сочетании с гипертонической болезнью |
| SI2189442T1 (sl) | 2008-11-20 | 2015-03-31 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Postopek in intermediati za pripravo aliskirena |
| CA2755047C (en) * | 2009-03-11 | 2018-12-04 | Promedior, Inc. | Treatment methods for autoimmune disorders |
| PT2405928T (pt) * | 2009-03-11 | 2017-02-07 | Promedior Inc | Métodos de tratamento e de diagnóstico para patologias de hipersensibilidade |
| UA110323C2 (en) * | 2009-06-04 | 2015-12-25 | Promedior Inc | Derivative of serum amyloid p and their receipt and application |
| AU2010262847B2 (en) * | 2009-06-17 | 2016-06-02 | Promedior, Inc. | SAP variants and their use |
| EP2510928A1 (en) | 2011-04-15 | 2012-10-17 | Almirall, S.A. | Aclidinium for use in improving the quality of sleep in respiratory patients |
| CN102247344A (zh) * | 2011-05-30 | 2011-11-23 | 北京阜康仁生物制药科技有限公司 | 一种新型降血压组合物 |
| CN102552277A (zh) * | 2011-12-02 | 2012-07-11 | 邬林祥 | 氨氯地平、阿利可仑和氢氯噻嗪复方降压药物 |
| CN102626391B (zh) * | 2012-04-19 | 2013-07-10 | 海南美兰史克制药有限公司 | 一种阿利克仑氢氯噻嗪药物组合物脂质体固体制剂 |
| GB201317373D0 (en) | 2013-10-01 | 2013-11-13 | Univ Dundee | Treatment and prevention of cancer |
| CN111789843A (zh) * | 2019-04-08 | 2020-10-20 | 深圳奥萨医药有限公司 | 含氨氯地平、氯噻酮和阿米洛利的药物组合物 |
| KR102414285B1 (ko) * | 2020-06-02 | 2022-06-28 | 이화여자대학교 산학협력단 | 플루나리진 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 골질환의 예방 또는 치료용 약학적 조성물 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5350771A (en) * | 1989-03-22 | 1994-09-27 | Peter K. T. Pang | Method and treatment for hypertension using combination therapy involving exogenous calcium and calcium channel blockers |
| US5656650A (en) * | 1990-12-14 | 1997-08-12 | Smithkline Beecham Corp. | Angiotensin II receptor blocking compositions |
| JP3398379B2 (ja) * | 1990-12-14 | 2003-04-21 | スミスクライン・ビーチャム・コーポレイション | アンジオテンシンｉｉ受容体遮断組成物 |
| US5178877A (en) * | 1991-01-04 | 1993-01-12 | Abbott Laboratories | Encapsulated renin inhibitor composition |
| US5114925A (en) * | 1991-01-22 | 1992-05-19 | Merck & Co., Inc. | Renin inhibitors containing the 2-[[(2R,3S)-3-amino-4-cyclohexyl-2-hydroxy-1-butyl]thio)alkanoyl moiety and the corresponding sulfoxide and sulfone derivatives |
| US5256667A (en) * | 1991-09-25 | 1993-10-26 | Merck & Co., Inc. | Quinazolinones and pyridopyrimidinones |
| US5202322A (en) * | 1991-09-25 | 1993-04-13 | Merck & Co., Inc. | Quinazolinone and pyridopyrimidine a-II antagonists |
| US5292741A (en) * | 1992-08-18 | 1994-03-08 | Merck & Co., Inc. | Macrocycles incorporating quinazolinones |
| MY119161A (en) | 1994-04-18 | 2005-04-30 | Novartis Ag | Delta-amino-gamma-hydroxy-omega-aryl-alkanoic acid amides with enzyme especially renin inhibiting activities |
| EP0795327A1 (en) * | 1996-03-13 | 1997-09-17 | Pfizer Inc. | Use of Amlodipine for the treatment and prophylaxis of congestive cardiac failure of non-ischaemic origin |
| US8168616B1 (en) * | 2000-11-17 | 2012-05-01 | Novartis Ag | Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension |
| CA2430924A1 (en) * | 2000-12-01 | 2002-06-06 | Novartis Ag | Angiotensin receptor antagonist composition for the treatment of sexual dysfunction associated with hypertension and another condition |
| EP1426051B1 (en) * | 2001-09-11 | 2008-07-16 | Asahi Kasei Pharma Corporation | Medicinal composition for prevention of or treatment for cerebrovascular disorder |
| US7019010B2 (en) * | 2001-09-27 | 2006-03-28 | Novertis Ag | Combinations |
| ES2369216T3 (es) * | 2002-05-17 | 2011-11-28 | Novartis Pharma Ag | Composición farmacéutica que comprende un inhibidor de renina, un bloqueador del canal de calcio y un diurético. |
-
2003
- 2003-05-16 ES ES03730064T patent/ES2369216T3/es not_active Expired - Lifetime
- 2003-05-16 AT AT03730064T patent/ATE520417T1/de active
- 2003-05-16 CN CNA03811237XA patent/CN1655819A/zh active Pending
- 2003-05-16 NZ NZ536555A patent/NZ536555A/en not_active IP Right Cessation
- 2003-05-16 SI SI200332071T patent/SI1507558T1/sl unknown
- 2003-05-16 DK DK03730064.7T patent/DK1507558T3/da active
- 2003-05-16 JP JP2004505094A patent/JP5288678B2/ja not_active Expired - Fee Related
- 2003-05-16 CA CA2485081A patent/CA2485081C/en not_active Expired - Fee Related
- 2003-05-16 AU AU2003240669A patent/AU2003240669B2/en not_active Ceased
- 2003-05-16 WO PCT/EP2003/005188 patent/WO2003097098A1/en not_active Ceased
- 2003-05-16 EP EP03730064A patent/EP1507558B8/en not_active Expired - Lifetime
- 2003-05-16 RU RU2004137104/15A patent/RU2316318C2/ru not_active IP Right Cessation
- 2003-05-16 BR BR0310084-7A patent/BR0310084A/pt not_active Application Discontinuation
- 2003-05-16 KR KR1020137023159A patent/KR20130109244A/ko not_active Ceased
- 2003-05-16 PL PL372203A patent/PL219032B1/pl unknown
- 2003-05-16 PT PT03730064T patent/PT1507558E/pt unknown
- 2003-05-16 EP EP10177741A patent/EP2316488A1/en not_active Withdrawn
- 2003-05-16 US US10/514,683 patent/US20050182042A1/en not_active Abandoned
- 2003-05-16 MX MXPA04011383A patent/MXPA04011383A/es active IP Right Grant
- 2003-05-16 KR KR1020107028689A patent/KR20100137026A/ko not_active Ceased
- 2003-05-16 KR KR10-2004-7018479A patent/KR20050008717A/ko not_active Ceased
-
2004
- 2004-10-19 ZA ZA200408442A patent/ZA200408442B/en unknown
- 2004-10-25 IL IL164837A patent/IL164837A/en not_active IP Right Cessation
- 2004-11-12 EC EC2004005428A patent/ECSP045428A/es unknown
- 2004-12-15 NO NO20045459A patent/NO334382B1/no not_active IP Right Cessation
-
2008
- 2008-08-08 US US12/188,604 patent/US8183295B2/en not_active Expired - Fee Related
-
2010
- 2010-08-13 JP JP2010181380A patent/JP2010280708A/ja not_active Withdrawn
-
2011
- 2011-11-07 CY CY20111101071T patent/CY1112013T1/el unknown
- 2011-11-30 US US13/307,567 patent/US20120071470A1/en not_active Abandoned
-
2012
- 2012-05-14 CY CY2012011C patent/CY2012011I1/el unknown
- 2012-05-14 LU LU92000C patent/LU92000I2/fr unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5288678B2 (ja) | レニンインヒビター、カルシウムチャネルブロッカーおよび利尿薬を含む医薬組成物 | |
| US8404744B2 (en) | Methods of treatment and pharmaceutical composition | |
| JP4820056B2 (ja) | バルサルタンおよびｎｅｐ阻害剤を含む医薬組成物 | |
| WO2007106708A2 (en) | Combinations of the angiotensin ii antagonist valsartan and the nep inhibitor daglutril | |
| JP2008530101A (ja) | 有機化合物の組合わせ剤 | |
| WO2007045663A2 (en) | Combination of an ati receptor antagonist and a np inhibitor fro treating ia hypertension and heartfailure | |
| HK1156212A (en) | Pharmaceutical composition comprising a renin inhibitor, a calcium channel blocker and a diuretic | |
| HK1074774B (en) | Pharmaceutical composition comprising a renin inhibitor, a calcium channel blocker and a diuretic |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060511 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060511 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090901 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091201 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091208 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091228 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100201 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20100225 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100303 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100413 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20101014 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130318 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130604 |
|
| LAPS | Cancellation because of no payment of annual fees |