ZA200601804B - Pharmaceutcal composition comprising a selective II imidazoline receptor agonist and an angiotensin II receptor blocker - Google Patents
Pharmaceutcal composition comprising a selective II imidazoline receptor agonist and an angiotensin II receptor blocker Download PDFInfo
- Publication number
- ZA200601804B ZA200601804B ZA200601804A ZA200601804A ZA200601804B ZA 200601804 B ZA200601804 B ZA 200601804B ZA 200601804 A ZA200601804 A ZA 200601804A ZA 200601804 A ZA200601804 A ZA 200601804A ZA 200601804 B ZA200601804 B ZA 200601804B
- Authority
- ZA
- South Africa
- Prior art keywords
- moxonidine
- eprosartan
- hypertension
- pharmaceutical composition
- angiotensin
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 20
- 229940123749 Imidazoline receptor agonist Drugs 0.000 title claims description 23
- 239000003087 receptor blocking agent Substances 0.000 title claims description 18
- 108050000824 Angiotensin II receptor Proteins 0.000 title abstract description 5
- 102000008873 Angiotensin II receptor Human genes 0.000 title abstract description 5
- WPNJAUFVNXKLIM-UHFFFAOYSA-N Moxonidine Chemical compound COC1=NC(C)=NC(Cl)=C1NC1=NCCN1 WPNJAUFVNXKLIM-UHFFFAOYSA-N 0.000 claims abstract description 103
- 229960003938 moxonidine Drugs 0.000 claims abstract description 98
- 206010020772 Hypertension Diseases 0.000 claims abstract description 94
- 238000011282 treatment Methods 0.000 claims abstract description 50
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 47
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 16
- 229960000573 eprosartan mesylate Drugs 0.000 claims abstract description 8
- DJSLTDBPKHORNY-XMMWENQYSA-N eprosartan methanesulfonate Chemical compound CS(O)(=O)=O.C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 DJSLTDBPKHORNY-XMMWENQYSA-N 0.000 claims abstract description 8
- 239000002080 C09CA02 - Eprosartan Substances 0.000 claims description 75
- 229960004563 eprosartan Drugs 0.000 claims description 75
- OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 claims description 73
- 239000003814 drug Substances 0.000 claims description 41
- 102000015427 Angiotensins Human genes 0.000 claims description 38
- 108010064733 Angiotensins Proteins 0.000 claims description 38
- 206010012601 diabetes mellitus Diseases 0.000 claims description 31
- 206010042957 Systolic hypertension Diseases 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 239000002934 diuretic Substances 0.000 claims description 16
- 230000001882 diuretic effect Effects 0.000 claims description 14
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 claims description 14
- 206010019280 Heart failures Diseases 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 230000002503 metabolic effect Effects 0.000 claims description 11
- 239000002083 C09CA01 - Losartan Substances 0.000 claims description 10
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims description 9
- 206010022489 Insulin Resistance Diseases 0.000 claims description 9
- 229960002198 irbesartan Drugs 0.000 claims description 9
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 claims description 9
- 101800000734 Angiotensin-1 Proteins 0.000 claims description 8
- 102400000344 Angiotensin-1 Human genes 0.000 claims description 8
- 230000006735 deficit Effects 0.000 claims description 8
- 201000001421 hyperglycemia Diseases 0.000 claims description 8
- 229960004773 losartan Drugs 0.000 claims description 8
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 claims description 8
- KCTFTBCZZUBAKN-UHFFFAOYSA-N pratosartan Chemical compound CCCC1=NC=2CCCCC(=O)C=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 KCTFTBCZZUBAKN-UHFFFAOYSA-N 0.000 claims description 8
- UBLHYKNVKKEDSV-UHFFFAOYSA-N 2-(4,5-dihydro-1h-imidazol-2-yl)-1,4-di(propan-2-yl)piperazine Chemical compound C1N(C(C)C)CCN(C(C)C)C1C1=NCCN1 UBLHYKNVKKEDSV-UHFFFAOYSA-N 0.000 claims description 7
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims description 7
- 239000002053 C09CA06 - Candesartan Substances 0.000 claims description 7
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims description 7
- 239000005477 Pratosartan Substances 0.000 claims description 7
- CQXADFVORZEARL-UHFFFAOYSA-N Rilmenidine Chemical compound C1CC1C(C1CC1)NC1=NCCO1 CQXADFVORZEARL-UHFFFAOYSA-N 0.000 claims description 7
- 229960000932 candesartan Drugs 0.000 claims description 7
- 229950005649 pratosartan Drugs 0.000 claims description 7
- 229960000764 rilmenidine Drugs 0.000 claims description 7
- 229960005187 telmisartan Drugs 0.000 claims description 7
- 229960004699 valsartan Drugs 0.000 claims description 7
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 claims description 7
- 239000005480 Olmesartan Substances 0.000 claims description 6
- 206010062237 Renal impairment Diseases 0.000 claims description 6
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 claims description 6
- 229960005117 olmesartan Drugs 0.000 claims description 6
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 5
- 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 claims description 5
- 150000004103 eprosartan derivatives Chemical class 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims 1
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 claims 1
- 230000001631 hypertensive effect Effects 0.000 abstract description 22
- 229940083183 imidazoline receptor agonists Drugs 0.000 abstract description 12
- 239000013543 active substance Substances 0.000 description 45
- 230000036772 blood pressure Effects 0.000 description 34
- 150000001875 compounds Chemical class 0.000 description 34
- 238000000034 method Methods 0.000 description 32
- 229940079593 drug Drugs 0.000 description 30
- 230000000694 effects Effects 0.000 description 26
- 239000003826 tablet Substances 0.000 description 24
- 239000002552 dosage form Substances 0.000 description 22
- 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 21
- -1 2-Bromophenoxy Chemical group 0.000 description 20
- 239000008103 glucose Substances 0.000 description 19
- 102000005962 receptors Human genes 0.000 description 19
- 108020003175 receptors Proteins 0.000 description 19
- 241001465754 Metazoa Species 0.000 description 18
- 239000000463 material Substances 0.000 description 15
- 235000002639 sodium chloride Nutrition 0.000 description 15
- 239000002464 receptor antagonist Substances 0.000 description 14
- 229940044551 receptor antagonist Drugs 0.000 description 14
- 108010049134 Imidazoline Receptors Proteins 0.000 description 13
- 102000009032 Imidazoline Receptors Human genes 0.000 description 13
- 210000002381 plasma Anatomy 0.000 description 13
- 230000036454 renin-angiotensin system Effects 0.000 description 12
- 229940097420 Diuretic Drugs 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 238000002648 combination therapy Methods 0.000 description 9
- 229960002003 hydrochlorothiazide Drugs 0.000 description 9
- 210000002820 sympathetic nervous system Anatomy 0.000 description 9
- 230000004913 activation Effects 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 229940030600 antihypertensive agent Drugs 0.000 description 8
- 239000002220 antihypertensive agent Substances 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 230000035488 systolic blood pressure Effects 0.000 description 8
- 230000003276 anti-hypertensive effect Effects 0.000 description 7
- 238000000576 coating method Methods 0.000 description 7
- 230000035487 diastolic blood pressure Effects 0.000 description 7
- 239000002207 metabolite Substances 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 230000002889 sympathetic effect Effects 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 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 6
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 6
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 6
- 102100028255 Renin Human genes 0.000 description 6
- 108090000783 Renin Proteins 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 235000010980 cellulose Nutrition 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 239000006186 oral dosage form Substances 0.000 description 6
- 210000002254 renal artery Anatomy 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 239000012730 sustained-release form Substances 0.000 description 6
- 230000002195 synergetic effect Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 description 5
- 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 5
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 230000003111 delayed effect Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 150000002462 imidazolines Chemical class 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 201000001474 proteinuria Diseases 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 238000013268 sustained release Methods 0.000 description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 4
- 239000005541 ACE inhibitor Substances 0.000 description 4
- 102000005862 Angiotensin II Human genes 0.000 description 4
- 101800000733 Angiotensin-2 Proteins 0.000 description 4
- 208000002705 Glucose Intolerance Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229940081735 acetylcellulose Drugs 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 4
- 229950006323 angiotensin ii Drugs 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 229920002301 cellulose acetate Polymers 0.000 description 4
- 208000020832 chronic kidney disease Diseases 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000001647 drug administration Methods 0.000 description 4
- 239000000890 drug combination Substances 0.000 description 4
- 230000001077 hypotensive effect Effects 0.000 description 4
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000007726 management method Methods 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 229940083254 peripheral vasodilators imidazoline derivative Drugs 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 201000009104 prediabetes syndrome Diseases 0.000 description 4
- 238000009097 single-agent therapy Methods 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 238000011680 zucker rat Methods 0.000 description 4
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 3
- 101150059573 AGTR1 gene Proteins 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 208000007530 Essential hypertension Diseases 0.000 description 3
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- 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 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229920001800 Shellac Polymers 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 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 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 229960004349 candesartan cilexetil Drugs 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940000425 combination drug Drugs 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 108010070995 imidazoline I1 receptors Proteins 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 201000006370 kidney failure Diseases 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 230000002644 neurohormonal effect Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 3
- 150000004885 piperazines Chemical class 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 229940044601 receptor agonist Drugs 0.000 description 3
- 239000000018 receptor agonist Substances 0.000 description 3
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 3
- 239000004208 shellac Substances 0.000 description 3
- 229940113147 shellac Drugs 0.000 description 3
- 235000013874 shellac Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000000948 sympatholitic effect Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- MYTRGMPNAUVEIU-UHFFFAOYSA-N 1-(4,5-dihydro-1h-imidazol-2-yl)isoquinoline Chemical compound N1CCN=C1C1=NC=CC2=CC=CC=C12 MYTRGMPNAUVEIU-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- RPRNBLHRKYAXSM-UHFFFAOYSA-N 2-ethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]-5,6,7,8-tetrahydroquinoline;hydrochloride Chemical compound Cl.C=12CCCCC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 RPRNBLHRKYAXSM-UHFFFAOYSA-N 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229920003084 Avicel® PH-102 Polymers 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 208000020401 Depressive disease Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108010061435 Enalapril Proteins 0.000 description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 108010083387 Saralasin Proteins 0.000 description 2
- 206010039897 Sedation Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 229940125364 angiotensin receptor blocker Drugs 0.000 description 2
- 230000002058 anti-hyperglycaemic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- 239000000480 calcium channel blocker Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000007894 caplet Substances 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 150000003943 catecholamines Chemical class 0.000 description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
- 239000008199 coating composition Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000007907 direct compression Methods 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940030606 diuretics Drugs 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 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 2
- 229960000873 enalapril Drugs 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000014101 glucose homeostasis Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229960000519 losartan potassium Drugs 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 201000003102 mental depression Diseases 0.000 description 2
- 229960002817 metolazone Drugs 0.000 description 2
- 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 2
- 210000002569 neuron Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 230000001603 reducing effect Effects 0.000 description 2
- 230000029865 regulation of blood pressure Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
- 125000005591 trimellitate group Chemical group 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- WJXAVNPIJIPGMN-PNGYUKAISA-N (2s)-2-[[(2s)-1-[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-methoxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]py 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](CCCN=C(N)N)NC(=O)CNC)C(C)C)C1=CC=C(OC)C=C1 WJXAVNPIJIPGMN-PNGYUKAISA-N 0.000 description 1
- GGKXIITZBSPCQP-IZIWAXSGSA-N (2s,4s,5s)-5-[[(2s)-2-[[(2s)-2-benzyl-3-tert-butylsulfonylpropanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-n-butyl-6-cyclohexyl-4-hydroxy-2-propan-2-ylhexanamide Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)NCCCC)C(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)CS(=O)(=O)C(C)(C)C)C1CCCCC1 GGKXIITZBSPCQP-IZIWAXSGSA-N 0.000 description 1
- IZQCLVVNYNAYBS-UHFFFAOYSA-N (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-cyclopropyl-3-[4-[2-(2h-tetrazol-5-yl)phenyl]phenoxy]quinoline-4-carboxylate Chemical compound O1C(=O)OC(COC(=O)C=2C3=CC=CC=C3N=C(C=2OC=2C=CC(=CC=2)C=2C(=CC=CC=2)C2=NNN=N2)C2CC2)=C1C IZQCLVVNYNAYBS-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- QFCJEMBKXJNJTL-UHFFFAOYSA-N 1-[(2,4-dichlorophenyl)methyl]-2-(4,5-dihydro-1h-imidazol-2-yl)-4-methylpiperazine Chemical compound N=1CCNC=1C1CN(C)CCN1CC1=CC=C(Cl)C=C1Cl QFCJEMBKXJNJTL-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- NPLSMQWSKZXZPD-UHFFFAOYSA-N 2,3-dihydropyrrol-1-amine Chemical class NN1CCC=C1 NPLSMQWSKZXZPD-UHFFFAOYSA-N 0.000 description 1
- UKEZYWUWLICNPR-UHFFFAOYSA-N 2,6-dibutyl-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-1h-pyrimidin-4-one Chemical compound N1C(CCCC)=NC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C2=NNN=N2)=C1CCCC UKEZYWUWLICNPR-UHFFFAOYSA-N 0.000 description 1
- LASWNZRBIPFGHP-UHFFFAOYSA-N 2,7-diethyl-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrazolo[1,5-b][1,2,4]triazole Chemical compound N12N=C(CC)N=C2C(CC)=CN1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 LASWNZRBIPFGHP-UHFFFAOYSA-N 0.000 description 1
- ABOVEHVFBQZNEN-UHFFFAOYSA-N 2-(4,5-dihydro-1h-imidazol-2-yl)-1,2-di(propan-2-yl)piperazine Chemical compound CC(C)N1CCNCC1(C(C)C)C1=NCCN1 ABOVEHVFBQZNEN-UHFFFAOYSA-N 0.000 description 1
- LQRYGEQNLPCYDT-FPYGCLRLSA-N 2-[4-[[2-[(e)-but-1-enyl]-4-chloro-5-(hydroxymethyl)imidazol-1-yl]methyl]phenyl]benzoic acid Chemical compound CC\C=C\C1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C(O)=O)C=C1 LQRYGEQNLPCYDT-FPYGCLRLSA-N 0.000 description 1
- UUPNFNCKGJOLQE-UHFFFAOYSA-N 2-[4-[[2-butyl-4-chloro-5-(hydroxymethyl)imidazol-1-yl]methyl]phenyl]benzoic acid Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C(O)=O)C=C1 UUPNFNCKGJOLQE-UHFFFAOYSA-N 0.000 description 1
- OLQFKFSAJNUOPT-UHFFFAOYSA-N 2-[4-[[2-butyl-6-(cyclohexylcarbamoylamino)benzimidazol-1-yl]methyl]phenyl]benzoic acid Chemical compound C1=C2N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C(O)=O)C(CCCC)=NC2=CC=C1NC(=O)NC1CCCCC1 OLQFKFSAJNUOPT-UHFFFAOYSA-N 0.000 description 1
- ZHWGRXBJGUEATA-UHFFFAOYSA-N 2-[[4-[[2-butyl-6-[methylcarbamoyl(pentyl)amino]benzimidazol-1-yl]methyl]phenyl]carbamoyl]-3,6-dichlorobenzoic acid Chemical compound C12=CC(N(C(=O)NC)CCCCC)=CC=C2N=C(CCCC)N1CC(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC(Cl)=C1C(O)=O ZHWGRXBJGUEATA-UHFFFAOYSA-N 0.000 description 1
- ZGAFRHMPMVKTNA-UHFFFAOYSA-N 2-[[4-butyl-2-methyl-6-oxo-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-1-yl]methyl]benzoic acid Chemical compound O=C1C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2NN=NN=2)=C(CCCC)N=C(C)N1CC1=CC=CC=C1C(O)=O ZGAFRHMPMVKTNA-UHFFFAOYSA-N 0.000 description 1
- YILJWHUIUCRKEU-UHFFFAOYSA-N 2-butyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-b]pyridine Chemical compound CCCCC1=NC2=CC=CN=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 YILJWHUIUCRKEU-UHFFFAOYSA-N 0.000 description 1
- AIGVXGCHRIOQNR-UHFFFAOYSA-N 2-butyl-5-chloro-3-[[1-[2-(2h-tetrazol-5-yl)phenyl]indol-4-yl]methyl]imidazole-4-carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=CC2=C1C=CN2C1=CC=CC=C1C1=NNN=N1 AIGVXGCHRIOQNR-UHFFFAOYSA-N 0.000 description 1
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
- MGSBGAVGFLLRDU-UHFFFAOYSA-N 2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5-[2-(2,2,2-trifluoroacetyl)pyrrol-1-yl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(N2C(=CC=C2)C(=O)C(F)(F)F)=C(C(O)=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 MGSBGAVGFLLRDU-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- SZWREMOBIUBYDP-UHFFFAOYSA-N 4-[(2,4-dichlorophenyl)methyl]-2-(4,5-dihydro-1h-imidazol-2-yl)-1-methylpiperazine Chemical compound C1C(C=2NCCN=2)N(C)CCN1CC1=CC=C(Cl)C=C1Cl SZWREMOBIUBYDP-UHFFFAOYSA-N 0.000 description 1
- LBXHRAWDUMTPSE-AOOOYVTPSA-N 4-chloro-N-[(2S,6R)-2,6-dimethyl-1-piperidinyl]-3-sulfamoylbenzamide Chemical compound C[C@H]1CCC[C@@H](C)N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 LBXHRAWDUMTPSE-AOOOYVTPSA-N 0.000 description 1
- QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 description 1
- RQGDXPDTZWGCQI-UHFFFAOYSA-N 5-(1,1,2,2,2-pentafluoroethyl)-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(C(F)(F)C(F)(F)F)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 RQGDXPDTZWGCQI-UHFFFAOYSA-N 0.000 description 1
- LDILUHSYQQLZRC-UHFFFAOYSA-N 5-[[[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]-1h-indole-2-carbonyl]amino]methyl]-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(CNC(=O)C=2NC3=CC=CC(OCC(O)CNC(C)C)=C3C=2)=C(C(O)=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 LDILUHSYQQLZRC-UHFFFAOYSA-N 0.000 description 1
- OFYWYKMCRWMPPQ-UHFFFAOYSA-N 5-ethyl-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(CC)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 OFYWYKMCRWMPPQ-UHFFFAOYSA-N 0.000 description 1
- OLJAPHMBAMBVKL-UHFFFAOYSA-N 5-methyl-7-propyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-3h-[1,2,4]triazolo[1,5-c]pyrimidin-2-one Chemical compound CCCC=1N=C(C)N2NC(=O)N=C2C=1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 OLJAPHMBAMBVKL-UHFFFAOYSA-N 0.000 description 1
- UIYUUEDFAMZISF-FTBISJDPSA-N 6-chloro-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide;(2s)-3-methyl-2-[pentanoyl-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoic acid Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O.C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NNN=N1 UIYUUEDFAMZISF-FTBISJDPSA-N 0.000 description 1
- BKYKPTRYDKTTJY-UHFFFAOYSA-N 6-chloro-3-(cyclopentylmethyl)-1,1-dioxo-3,4-dihydro-2H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1CCCC1 BKYKPTRYDKTTJY-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 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 1
- 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 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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 1
- 102000004881 Angiotensinogen Human genes 0.000 description 1
- 108090001067 Angiotensinogen Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000002081 C09CA05 - Tasosartan Substances 0.000 description 1
- 108010076395 CGP 38560 Proteins 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229920003152 Eudragit® RS polymer Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000001953 Hypotension 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
- 229940116397 Imidazoline I1 receptor agonist Drugs 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- LINHZVMHXABQLB-ZDUSSCGKSA-N Isoboldine Chemical compound CN1CCC2=CC(OC)=C(O)C3=C2[C@@H]1CC1=C3C=C(OC)C(O)=C1 LINHZVMHXABQLB-ZDUSSCGKSA-N 0.000 description 1
- 108010078036 KRI 1177 Proteins 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- SMNOERSLNYGGOU-UHFFFAOYSA-N Mefruside Chemical compound C=1C=C(Cl)C(S(N)(=O)=O)=CC=1S(=O)(=O)N(C)CC1(C)CCCO1 SMNOERSLNYGGOU-UHFFFAOYSA-N 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- ZDJYWPQCNAPESX-UHFFFAOYSA-N Myrigalone H Chemical compound COC1=CC(O)=C(C)C(O)=C1C(=O)CCC1=CC=CC=C1 ZDJYWPQCNAPESX-UHFFFAOYSA-N 0.000 description 1
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
- 102100038995 Nischarin Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- UJEWTUDSLQGTOA-UHFFFAOYSA-N Piretanide Chemical compound C=1C=CC=CC=1OC=1C(S(=O)(=O)N)=CC(C(O)=O)=CC=1N1CCCC1 UJEWTUDSLQGTOA-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- CYLWJCABXYDINA-UHFFFAOYSA-N Polythiazide Polymers ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CSCC(F)(F)F)NC2=C1 CYLWJCABXYDINA-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010038378 Renal artery stenosis Diseases 0.000 description 1
- 206010063897 Renal ischaemia Diseases 0.000 description 1
- 239000005478 Saprisartan Substances 0.000 description 1
- DUEWVPTZCSAMNB-UHFFFAOYSA-N Saprisartan Chemical compound NC(=O)C=1N(CC=2C=C3C(Br)=C(OC3=CC=2)C=2C(=CC=CC=2)NS(=O)(=O)C(F)(F)F)C(CC)=NC=1C1CC1 DUEWVPTZCSAMNB-UHFFFAOYSA-N 0.000 description 1
- 108700028065 Sar(1)-Me-Tyr(4)- angiotensin II Proteins 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 208000008253 Systolic Heart Failure Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 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
- 229920002494 Zein Polymers 0.000 description 1
- TYVWBCMQECJNSK-UHFFFAOYSA-N [2-methyl-3-(2-methylprop-2-enoyloxy)butan-2-yl]azanium;chloride Chemical compound [Cl-].CC([NH3+])(C)C(C)OC(=O)C(C)=C TYVWBCMQECJNSK-UHFFFAOYSA-N 0.000 description 1
- ZUMPSVPHCDJCMD-UHFFFAOYSA-N abitesartan Chemical compound C1CCCC1(C(O)=O)CN(C(=O)CCCC)CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ZUMPSVPHCDJCMD-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- YBZYNINTWCLDQA-UHKVWXOHSA-N acetic acid;(2s)-2-[[(2s)-1-[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-(1h-imidazol-5-yl)prop Chemical compound O.CC(O)=O.C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)C1=CC=C(O)C=C1 YBZYNINTWCLDQA-UHKVWXOHSA-N 0.000 description 1
- 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 1
- AEMQUICCWRPKDB-UHFFFAOYSA-N acetic acid;cyclohexane-1,2-dicarboxylic acid Chemical compound CC(O)=O.OC(=O)C1CCCCC1C(O)=O AEMQUICCWRPKDB-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 210000001943 adrenal medulla Anatomy 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000003513 alkali Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
- 229960002576 amiloride Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000400 angiotensin II type 1 receptor blocker Substances 0.000 description 1
- 229940127282 angiotensin receptor antagonist Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940046545 animal allergen extract Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 208000037849 arterial hypertension Diseases 0.000 description 1
- 229960004988 azosemide Drugs 0.000 description 1
- IIOPLILENRZKRV-UHFFFAOYSA-N azosemide Chemical compound C=1C=CSC=1CNC=1C=C(Cl)C(S(=O)(=O)N)=CC=1C1=NN=N[N]1 IIOPLILENRZKRV-UHFFFAOYSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 229960003515 bendroflumethiazide Drugs 0.000 description 1
- HDWIHXWEUNVBIY-UHFFFAOYSA-N bendroflumethiazidum Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1=CC=CC=C1 HDWIHXWEUNVBIY-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960001541 benzthiazide Drugs 0.000 description 1
- NDTSRXAMMQDVSW-UHFFFAOYSA-N benzthiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1N=C2CSCC1=CC=CC=C1 NDTSRXAMMQDVSW-UHFFFAOYSA-N 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 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
- 229960004064 bumetanide Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- VHEMBTYWURNBQQ-UHFFFAOYSA-N butanoic acid;phthalic acid Chemical compound CCCC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O VHEMBTYWURNBQQ-UHFFFAOYSA-N 0.000 description 1
- ULBTUVJTXULMLP-UHFFFAOYSA-N butyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCC ULBTUVJTXULMLP-UHFFFAOYSA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229940106135 cellulose Drugs 0.000 description 1
- 229920001727 cellulose butyrate Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229960002155 chlorothiazide Drugs 0.000 description 1
- 229960001523 chlortalidone Drugs 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229960004070 clopamide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- QSAWQNUELGIYBC-UHFFFAOYSA-N cyclohexane-1,2-dicarboxylic acid Chemical compound OC(=O)C1CCCCC1C(O)=O QSAWQNUELGIYBC-UHFFFAOYSA-N 0.000 description 1
- 229960003206 cyclopenthiazide Drugs 0.000 description 1
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical class NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
- 229960003176 cyclothiazide Drugs 0.000 description 1
- BOCUKUHCLICSIY-QJWLJZLASA-N cyclothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2C1[C@H](C=C2)C[C@H]2C1 BOCUKUHCLICSIY-QJWLJZLASA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 229960005081 diclofenamide Drugs 0.000 description 1
- GJQPMPFPNINLKP-UHFFFAOYSA-N diclofenamide Chemical compound NS(=O)(=O)C1=CC(Cl)=C(Cl)C(S(N)(=O)=O)=C1 GJQPMPFPNINLKP-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- CCYTUJPXAFHZHC-UHFFFAOYSA-L disodium;4-[[2-butyl-5-(carboxylatomethyl)-4-chloroimidazol-1-yl]methyl]benzoate Chemical compound [Na+].[Na+].CCCCC1=NC(Cl)=C(CC([O-])=O)N1CC1=CC=C(C([O-])=O)C=C1 CCYTUJPXAFHZHC-UHFFFAOYSA-L 0.000 description 1
- IAVUPMFITXYVAF-XPUUQOCRSA-N dorzolamide Chemical compound CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 IAVUPMFITXYVAF-XPUUQOCRSA-N 0.000 description 1
- 229960003933 dorzolamide Drugs 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- IDAWWPOAHPVPMY-UHFFFAOYSA-N elisartan Chemical compound CCCCC1=NC(Cl)=C(C(=O)OC(C)OC(=O)OCC)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 IDAWWPOAHPVPMY-UHFFFAOYSA-N 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 201000000523 end stage renal failure Diseases 0.000 description 1
- 230000007368 endocrine function Effects 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 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
- 229940011916 ethacrynate sodium Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 229950005098 ethoxzolamide Drugs 0.000 description 1
- OUZWUKMCLIBBOG-UHFFFAOYSA-N ethoxzolamide Chemical compound CCOC1=CC=C2N=C(S(N)(=O)=O)SC2=C1 OUZWUKMCLIBBOG-UHFFFAOYSA-N 0.000 description 1
- JBEUFWOCGLXNCS-XSFVSMFZSA-N ethyl (2e)-2-[4-ethyl-4-methyl-6-oxo-1-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]piperidin-2-ylidene]acetate Chemical compound CCOC(=O)\C=C1/CC(C)(CC)CC(=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 JBEUFWOCGLXNCS-XSFVSMFZSA-N 0.000 description 1
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 1
- FSXVSUSRJXIJHB-UHFFFAOYSA-M ethyl prop-2-enoate;methyl 2-methylprop-2-enoate;trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CCOC(=O)C=C.COC(=O)C(C)=C.CC(=C)C(=O)OCC[N+](C)(C)C FSXVSUSRJXIJHB-UHFFFAOYSA-M 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 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
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 230000010030 glucose lowering effect Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 229960003313 hydroflumethiazide Drugs 0.000 description 1
- DMDGGSIALPNSEE-UHFFFAOYSA-N hydroflumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O DMDGGSIALPNSEE-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229960004569 indapamide Drugs 0.000 description 1
- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000002650 laminated plastic Substances 0.000 description 1
- ZEUXAIYYDDCIRX-UHFFFAOYSA-N losartan carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 ZEUXAIYYDDCIRX-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960004678 mefruside Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- FLOSMHQXBMRNHR-DAXSKMNVSA-N methazolamide Chemical compound CC(=O)\N=C1/SC(S(N)(=O)=O)=NN1C FLOSMHQXBMRNHR-DAXSKMNVSA-N 0.000 description 1
- 229960004083 methazolamide Drugs 0.000 description 1
- UQUFRFSCUYVXBM-UHFFFAOYSA-N methyl 2-hydroxy-3-[[3-(1h-imidazol-5-yl)-2-[[2-(naphthalen-1-ylmethyl)-4-oxo-4-(2-phenylethylamino)butanoyl]amino]propanoyl]amino]-5-methylhexanoate Chemical compound C=1C=CC=CC=1CCNC(=O)CC(CC=1C2=CC=CC=C2C=CC=1)C(=O)NC(C(=O)NC(CC(C)C)C(O)C(=O)OC)CC1=CN=CN1 UQUFRFSCUYVXBM-UHFFFAOYSA-N 0.000 description 1
- AWIVWBRKOUQKEI-UHFFFAOYSA-N methyl 3-[[4-[2-(butoxycarbonylsulfamoyl)phenyl]-2-chlorophenyl]methyl]-5-ethyl-2-propylimidazole-4-carboxylate Chemical compound CCCCOC(=O)NS(=O)(=O)C1=CC=CC=C1C(C=C1Cl)=CC=C1CN1C(C(=O)OC)=C(CC)N=C1CCC AWIVWBRKOUQKEI-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 229920003087 methylethyl cellulose Polymers 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- BVZUBMFQVJEKKD-UHFFFAOYSA-N n-(4,5-dihydro-1h-imidazol-2-yl)pyrimidin-5-amine Chemical class N1CCN=C1NC1=CN=CN=C1 BVZUBMFQVJEKKD-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229960001199 olmesartan medoxomil Drugs 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 238000007410 oral glucose tolerance test Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940097258 other antihypertensives in atc Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-M phthalate(1-) Chemical compound OC(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-M 0.000 description 1
- 230000007180 physiological regulation Effects 0.000 description 1
- 229960001085 piretanide Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229960005483 polythiazide Drugs 0.000 description 1
- 229920000046 polythiazide Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229940075065 polyvinyl acetate Drugs 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- ADJDSKWTIYUCDV-UHFFFAOYSA-M potassium;2-butyl-5-methylsulfanyl-3-[[4-[2-(propylcarbamoylsulfamoyl)phenyl]phenyl]methyl]imidazole-4-carboxylate Chemical compound [K+].CCCCC1=NC(SC)=C(C([O-])=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC(=O)NCCC)C=C1 ADJDSKWTIYUCDV-UHFFFAOYSA-M 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229960000577 quinethazone Drugs 0.000 description 1
- AGMMTXLNIQSRCG-UHFFFAOYSA-N quinethazone Chemical compound NS(=O)(=O)C1=C(Cl)C=C2NC(CC)NC(=O)C2=C1 AGMMTXLNIQSRCG-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000005067 remediation Methods 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229950006241 saprisartan Drugs 0.000 description 1
- PFGWGEPQIUAZME-NXSMLHPHSA-N saralasin Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)C1=CC=C(O)C=C1 PFGWGEPQIUAZME-NXSMLHPHSA-N 0.000 description 1
- 229960004785 saralasin Drugs 0.000 description 1
- 229960001379 saralasin acetate Drugs 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- CWCSCNSKBSCYCS-UHFFFAOYSA-M sodium;2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetate Chemical compound [Na+].CCC(=C)C(=O)C1=CC=C(OCC([O-])=O)C(Cl)=C1Cl CWCSCNSKBSCYCS-UHFFFAOYSA-M 0.000 description 1
- OSDQJFVHDVAJSD-UHFFFAOYSA-M sodium;2-[2-butyl-3-[[4-[(2-carboxybenzoyl)amino]phenyl]methyl]-5-chloroimidazol-4-yl]propanoate Chemical compound [Na+].CCCCC1=NC(Cl)=C(C(C)C([O-])=O)N1CC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C(O)=O OSDQJFVHDVAJSD-UHFFFAOYSA-M 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000600 sorbitol Substances 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
- 229960002256 spironolactone Drugs 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960000651 tasosartan Drugs 0.000 description 1
- ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 description 1
- 229920001897 terpolymer Polymers 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 229960005461 torasemide Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229960001288 triamterene Drugs 0.000 description 1
- 229960004813 trichlormethiazide Drugs 0.000 description 1
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
- 229950004678 tripamide Drugs 0.000 description 1
- UHLOVGKIEARANS-QZHINBJYSA-N tripamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(=O)NN2C[C@@H]3[C@H]4CC[C@H](C4)[C@@H]3C2)=C1 UHLOVGKIEARANS-QZHINBJYSA-N 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920006163 vinyl copolymer Polymers 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 229960000537 xipamide Drugs 0.000 description 1
- MTZBBNMLMNBNJL-UHFFFAOYSA-N xipamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C1=CC(S(N)(=O)=O)=C(Cl)C=C1O MTZBBNMLMNBNJL-UHFFFAOYSA-N 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
- 229940093612 zein Drugs 0.000 description 1
- FIKYECRHLXONOX-UHFFFAOYSA-N zolasartan Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(OC(=C2Br)C=3C(=CC=CC=3)C3=NNN=N3)C2=C1 FIKYECRHLXONOX-UHFFFAOYSA-N 0.000 description 1
- 229950004433 zolasartan 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- 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
- A61P9/12—Antihypertensives
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03103763 | 2003-10-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200601804B true ZA200601804B (en) | 2007-05-30 |
Family
ID=34486329
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200601804A ZA200601804B (en) | 2003-10-10 | 2004-10-07 | Pharmaceutcal composition comprising a selective II imidazoline receptor agonist and an angiotensin II receptor blocker |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US20050143435A1 (ru) |
| EP (1) | EP1673107B1 (ru) |
| JP (1) | JP4829115B2 (ru) |
| KR (1) | KR101137084B1 (ru) |
| CN (1) | CN100453117C (ru) |
| AT (1) | ATE390148T1 (ru) |
| AU (1) | AU2004283047B2 (ru) |
| BR (1) | BRPI0415198A (ru) |
| CA (1) | CA2541867C (ru) |
| DE (1) | DE602004012763T2 (ru) |
| ES (1) | ES2304624T3 (ru) |
| HK (1) | HK1096293A1 (ru) |
| IL (1) | IL174762A (ru) |
| MX (1) | MXPA06004029A (ru) |
| NO (1) | NO335735B1 (ru) |
| PL (1) | PL1673107T3 (ru) |
| RU (1) | RU2362561C2 (ru) |
| UA (1) | UA83077C2 (ru) |
| WO (1) | WO2005039639A2 (ru) |
| ZA (1) | ZA200601804B (ru) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4675586B2 (ja) * | 2004-06-23 | 2011-04-27 | 壽製薬株式会社 | 高血圧症及び血清高尿酸血症の重複発症の治療のための薬剤 |
| CA2625646A1 (en) * | 2005-10-25 | 2007-05-03 | Merck & Co., Inc. | Combination of a dipeptidyl peptidase-4 inhibitor and an anti-hypertensive agent for the treatment of diabetes and hypertension |
| DE602007012692D1 (de) | 2006-06-16 | 2011-04-07 | Lek Pharmaceuticals | Pharmazeutische zusammensetzung mit hydrochlorothiazid und telmisartan |
| ATE497799T1 (de) | 2007-07-25 | 2011-02-15 | Schott Forma Vitrum Ag | Verabreichungsvorrichtung |
| EP2203158A4 (en) * | 2007-10-30 | 2012-12-26 | Reddys Lab Ltd Dr | PHARMACEUTICAL FORMULATIONS WITH TELMISARTAN AND HYDROCHLORTHIAZIDE |
| UA103688C2 (ru) * | 2009-06-30 | 2013-11-11 | Санофі | Твердые фармацевтические композиции с фиксированной дозой, содержащие ирбесартан и амлодипин, их получение и их терапевтическое применение |
| CN102850331B (zh) * | 2012-09-17 | 2015-05-20 | 符爱清 | 一种化合物的制备方法 |
| MD4412C1 (ru) * | 2014-08-29 | 2016-11-30 | Алёна ДУРНЯ | Использование 4-({2-бутил-5-[2-карбокси-2-(тиофен-2-илметил)ет-1-ен-1-ил]-1H-имидазол-1-ил}метил)бензойной кислоты для улучшения эластичности сосудов в профилактике осложнений гипертонического генеза |
| PL424452A1 (pl) * | 2018-01-31 | 2019-08-12 | Forty-Four Pharmaceuticals Spółka Z Ograniczoną Odpowiedzialnością | Inhibitory obojętnej endopeptydazy (NEP) i ludzkiej rozpuszczalnej endopeptydazy (hSEP) do profilaktyki i leczenia chorób oczu |
| RU2734281C1 (ru) * | 2019-06-11 | 2020-10-14 | Федеральное государственное бюджетное учреждение науки Институт теоретической и экспериментальной биофизики Российской академии наук (ИТЭБ РАН) | Композиция для лечения артериальной гипертензии и ассоциированных с ней патологий сердечно-сосудистой системы |
| WO2020257736A1 (en) * | 2019-06-21 | 2020-12-24 | The Broad Institute, Inc. | Agents for reversing toxic proteinopathies |
| GB202006074D0 (en) * | 2020-04-24 | 2020-06-10 | Vicore Pharma Ab | New composition |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5138069A (en) * | 1986-07-11 | 1992-08-11 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking imidazoles |
| US5354867A (en) * | 1988-12-06 | 1994-10-11 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking imidazoles |
| US5312828A (en) * | 1989-06-14 | 1994-05-17 | Finkelstein Joseph A | Substituted imidazoles having angiotensin II receptor blocking activity |
| US5185351A (en) * | 1989-06-14 | 1993-02-09 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids useful as angiotensin II receptor antagonists |
| DE59107440D1 (de) * | 1990-02-19 | 1996-04-04 | Ciba Geigy Ag | Acylverbindungen |
| US5270317A (en) * | 1990-03-20 | 1993-12-14 | Elf Sanofi | N-substituted heterocyclic derivatives, their preparation and the pharmaceutical compositions in which they are present |
| JP2707390B2 (ja) * | 1992-05-22 | 1998-01-28 | 壽製薬株式会社 | シクロヘプトイミダゾ−ル誘導体及びその製造方法並びにこれを含有する薬剤 |
| DE4423177A1 (de) * | 1994-07-01 | 1996-01-04 | Kali Chemie Pharma Gmbh | Antihyperglykämisch wirksame Arzneimittel |
| US5972948A (en) * | 1994-07-01 | 1999-10-26 | Solvay Pharmaceuticals Gmbh | Method of inhibiting hyperglycemia and pharmaceutical composition for use therein |
| NO980546L (no) * | 1997-02-11 | 1998-08-12 | Lilly Co Eli | Farmas°ytiske midler |
| US20030059471A1 (en) * | 1997-12-15 | 2003-03-27 | Compton Bruce Jon | Oral delivery formulation |
| US6235311B1 (en) * | 1998-03-18 | 2001-05-22 | Bristol-Myers Squibb Company | Pharmaceutical composition containing a combination of a statin and aspirin and method |
| JP4107831B2 (ja) * | 2000-11-21 | 2008-06-25 | 第一三共株式会社 | 医薬組成物 |
| US20030152622A1 (en) * | 2001-10-25 | 2003-08-14 | Jenny Louie-Helm | Formulation of an erodible, gastric retentive oral diuretic |
| HU0200980D0 (ru) * | 2002-03-14 | 2002-05-29 | Gabor S Pal Dr | |
| AU2003268493A1 (en) * | 2002-09-11 | 2004-04-30 | Merck & Co., Inc. | Piperazine urea derivatives as melanocortin-4 receptor agonists |
-
2004
- 2004-10-07 JP JP2006530280A patent/JP4829115B2/ja not_active Expired - Fee Related
- 2004-10-07 KR KR1020067006561A patent/KR101137084B1/ko not_active IP Right Cessation
- 2004-10-07 EP EP04766880A patent/EP1673107B1/en active Active
- 2004-10-07 US US10/959,317 patent/US20050143435A1/en not_active Abandoned
- 2004-10-07 MX MXPA06004029A patent/MXPA06004029A/es active IP Right Grant
- 2004-10-07 UA UAA200604846A patent/UA83077C2/ru unknown
- 2004-10-07 AT AT04766880T patent/ATE390148T1/de not_active IP Right Cessation
- 2004-10-07 BR BRPI0415198-4A patent/BRPI0415198A/pt not_active Application Discontinuation
- 2004-10-07 CA CA2541867A patent/CA2541867C/en not_active Expired - Fee Related
- 2004-10-07 ZA ZA200601804A patent/ZA200601804B/en unknown
- 2004-10-07 DE DE602004012763T patent/DE602004012763T2/de active Active
- 2004-10-07 WO PCT/EP2004/052468 patent/WO2005039639A2/en active IP Right Grant
- 2004-10-07 RU RU2006115796/15A patent/RU2362561C2/ru active
- 2004-10-07 ES ES04766880T patent/ES2304624T3/es active Active
- 2004-10-07 CN CNB2004800285299A patent/CN100453117C/zh not_active Expired - Fee Related
- 2004-10-07 PL PL04766880T patent/PL1673107T3/pl unknown
- 2004-10-07 AU AU2004283047A patent/AU2004283047B2/en not_active Ceased
-
2006
- 2006-04-04 IL IL174762A patent/IL174762A/en not_active IP Right Cessation
- 2006-05-09 NO NO20062088A patent/NO335735B1/no not_active IP Right Cessation
-
2007
- 2007-03-30 HK HK07103420.7A patent/HK1096293A1/xx not_active IP Right Cessation
-
2011
- 2011-05-26 US US13/116,620 patent/US20110229571A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| RU2362561C2 (ru) | 2009-07-27 |
| CA2541867C (en) | 2012-06-12 |
| AU2004283047B2 (en) | 2009-09-17 |
| IL174762A0 (en) | 2006-08-20 |
| RU2006115796A (ru) | 2007-11-27 |
| WO2005039639A2 (en) | 2005-05-06 |
| KR101137084B1 (ko) | 2012-04-24 |
| UA83077C2 (ru) | 2008-06-10 |
| WO2005039639B1 (en) | 2005-09-22 |
| NO20062088L (no) | 2006-07-07 |
| HK1096293A1 (en) | 2007-06-01 |
| ES2304624T3 (es) | 2008-10-16 |
| ATE390148T1 (de) | 2008-04-15 |
| JP4829115B2 (ja) | 2011-12-07 |
| JP2007508276A (ja) | 2007-04-05 |
| CN1859924A (zh) | 2006-11-08 |
| EP1673107B1 (en) | 2008-03-26 |
| DE602004012763D1 (de) | 2008-05-08 |
| BRPI0415198A (pt) | 2006-12-05 |
| CA2541867A1 (en) | 2005-05-06 |
| US20050143435A1 (en) | 2005-06-30 |
| KR20060117912A (ko) | 2006-11-17 |
| AU2004283047A1 (en) | 2005-05-06 |
| MXPA06004029A (es) | 2006-06-28 |
| US20110229571A1 (en) | 2011-09-22 |
| NO335735B1 (no) | 2015-02-02 |
| WO2005039639A3 (en) | 2005-08-11 |
| EP1673107A2 (en) | 2006-06-28 |
| DE602004012763T2 (de) | 2009-05-07 |
| IL174762A (en) | 2010-11-30 |
| PL1673107T3 (pl) | 2008-06-30 |
| CN100453117C (zh) | 2009-01-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20110229571A1 (en) | Pharmaceutical Compositions Comprising a Selective I1 Imidazoline Receptor Agonist and an Angiotensin II Receptor Blocker | |
| JP4870888B2 (ja) | 心血管の病態の予防におけるレニン−アンギオテンシン系阻害剤の使用 | |
| US6576256B2 (en) | Treatment of patients at elevated cardiovascular risk with a combination of a cholesterol-lowering agent, an inhibitor of the renin-angiotensin system, and aspirin | |
| RU2384346C2 (ru) | Фармацевтические композиции, содержащие nep-ингибиторы, ингибиторы эндогенной эндотелинпродуцирующей системы и антагонисты at1-рецептора | |
| JP2005504064A (ja) | コレステロール低下薬、レニン・アンギオテンシン阻害剤およびアスピリンを含有する組み合わせ剤形 | |
| WO2007053406A1 (en) | Combinations of antihypertensive and cholesterol lowering agents | |
| WO2007051007A2 (en) | Combination of antihypertensives with cholesterol-lowering agent | |
| CN100584382C (zh) | 含有血管紧张素ⅱ受体拮抗剂和苯氧酸类化合物的药物组合物 | |
| EP1611886A2 (en) | Inhibitors of the renin-angiotensin system for the prevention of cardiovascular disorders |