CN103566372A - Pharmaceutical composition for lowering blood pressure - Google Patents
Pharmaceutical composition for lowering blood pressure Download PDFInfo
- Publication number
- CN103566372A CN103566372A CN201210281577.5A CN201210281577A CN103566372A CN 103566372 A CN103566372 A CN 103566372A CN 201210281577 A CN201210281577 A CN 201210281577A CN 103566372 A CN103566372 A CN 103566372A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- ramipril
- pharmaceutical compositions
- azilsartan
- diuretic
- 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.)
- Pending
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 30
- 230000036772 blood pressure Effects 0.000 title abstract description 16
- KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000005485 Azilsartan Substances 0.000 claims abstract description 33
- 229960002731 azilsartan Drugs 0.000 claims abstract description 33
- 239000003814 drug Substances 0.000 claims abstract description 10
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical group C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 23
- 229960003401 ramipril Drugs 0.000 claims description 18
- KOHIRBRYDXPAMZ-YHBROIRLSA-N (S,R,R,R)-nebivolol Chemical compound C1CC2=CC(F)=CC=C2O[C@H]1[C@H](O)CNC[C@@H](O)[C@H]1OC2=CC=C(F)C=C2CC1 KOHIRBRYDXPAMZ-YHBROIRLSA-N 0.000 claims description 12
- 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 12
- 239000002934 diuretic Substances 0.000 claims description 12
- 230000001882 diuretic effect Effects 0.000 claims description 12
- 239000008187 granular material Substances 0.000 claims description 12
- 229960002003 hydrochlorothiazide Drugs 0.000 claims description 12
- 229960000619 nebivolol Drugs 0.000 claims description 12
- HTIQEAQVCYTUBX-KRWDZBQOSA-N (S)-amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-KRWDZBQOSA-N 0.000 claims description 11
- 229940077927 altace Drugs 0.000 claims description 11
- 229950008554 levamlodipine Drugs 0.000 claims description 11
- 239000005541 ACE inhibitor Substances 0.000 claims description 8
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 8
- 108010061435 Enalapril Proteins 0.000 claims description 8
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 8
- 239000000480 calcium channel blocker Substances 0.000 claims description 8
- 229960000873 enalapril Drugs 0.000 claims description 8
- 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 claims description 8
- 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 7
- 229960000528 amlodipine Drugs 0.000 claims description 7
- 239000002876 beta blocker Substances 0.000 claims description 7
- 229940097320 beta blocking agent Drugs 0.000 claims description 7
- 229960000830 captopril Drugs 0.000 claims description 7
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 claims description 7
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 claims description 6
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 claims description 6
- BHIAIPWSVYSKJS-UHFFFAOYSA-N arotinolol Chemical compound S1C(SCC(O)CNC(C)(C)C)=NC(C=2SC(=CC=2)C(N)=O)=C1 BHIAIPWSVYSKJS-UHFFFAOYSA-N 0.000 claims description 6
- 229950010731 arotinolol Drugs 0.000 claims description 6
- 229960002274 atenolol Drugs 0.000 claims description 6
- 229960003580 felodipine Drugs 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 claims description 2
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 claims description 2
- FHHHOYXPRDYHEZ-COXVUDFISA-N Alacepril Chemical compound CC(=O)SC[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FHHHOYXPRDYHEZ-COXVUDFISA-N 0.000 claims description 2
- 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 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- JOATXPAWOHTVSZ-UHFFFAOYSA-N Celiprolol Chemical compound CCN(CC)C(=O)NC1=CC=C(OCC(O)CNC(C)(C)C)C(C(C)=O)=C1 JOATXPAWOHTVSZ-UHFFFAOYSA-N 0.000 claims description 2
- IFYLTXNCFVRALQ-OALUTQOASA-N Ceronapril Chemical compound O([C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)P(O)(=O)CCCCC1=CC=CC=C1 IFYLTXNCFVRALQ-OALUTQOASA-N 0.000 claims description 2
- 229940097420 Diuretic Drugs 0.000 claims description 2
- 108010066671 Enalaprilat Proteins 0.000 claims description 2
- 108010007859 Lisinopril Proteins 0.000 claims description 2
- 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 claims description 2
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 claims description 2
- 229950007884 alacepril Drugs 0.000 claims description 2
- 230000008485 antagonism Effects 0.000 claims description 2
- 229960004530 benazepril Drugs 0.000 claims description 2
- 229960002781 bisoprolol Drugs 0.000 claims description 2
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229960004195 carvedilol Drugs 0.000 claims description 2
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 claims description 2
- 229960002320 celiprolol Drugs 0.000 claims description 2
- 229950005749 ceronapril Drugs 0.000 claims description 2
- 229960005025 cilazapril Drugs 0.000 claims description 2
- HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 229960005227 delapril Drugs 0.000 claims description 2
- WOUOLAUOZXOLJQ-MBSDFSHPSA-N delapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N(CC(O)=O)C1CC2=CC=CC=C2C1)CC1=CC=CC=C1 WOUOLAUOZXOLJQ-MBSDFSHPSA-N 0.000 claims description 2
- -1 draws card Horizon Chemical compound 0.000 claims description 2
- 229960002680 enalaprilat Drugs 0.000 claims description 2
- LZFZMUMEGBBDTC-QEJZJMRPSA-N enalaprilat (anhydrous) Chemical compound C([C@H](N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 LZFZMUMEGBBDTC-QEJZJMRPSA-N 0.000 claims description 2
- 229960002490 fosinopril Drugs 0.000 claims description 2
- 229960001632 labetalol Drugs 0.000 claims description 2
- 229960004340 lacidipine Drugs 0.000 claims description 2
- GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 claims description 2
- 229960002394 lisinopril Drugs 0.000 claims description 2
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 claims description 2
- 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 claims description 2
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 claims description 2
- 229960001597 nifedipine Drugs 0.000 claims description 2
- 229960005366 nilvadipine Drugs 0.000 claims description 2
- 229960000227 nisoldipine Drugs 0.000 claims description 2
- 229960002582 perindopril Drugs 0.000 claims description 2
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 claims description 2
- 229960001749 practolol Drugs 0.000 claims description 2
- DURULFYMVIFBIR-UHFFFAOYSA-N practolol Chemical compound CC(C)NCC(O)COC1=CC=C(NC(C)=O)C=C1 DURULFYMVIFBIR-UHFFFAOYSA-N 0.000 claims description 2
- 229960001455 quinapril Drugs 0.000 claims description 2
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 claims description 2
- KEDYTOTWMPBSLG-HILJTLORSA-N ramiprilat Chemical compound C([C@H](N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)C(O)=O)CC1=CC=CC=C1 KEDYTOTWMPBSLG-HILJTLORSA-N 0.000 claims description 2
- 229960002231 ramiprilat Drugs 0.000 claims description 2
- 229960002909 spirapril Drugs 0.000 claims description 2
- 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 claims description 2
- 108700035424 spirapril Proteins 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 229960004084 temocapril Drugs 0.000 claims description 2
- FIQOFIRCTOWDOW-BJLQDIEVSA-N temocapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C[C@H](SC1)C=1SC=CC=1)=O)CC1=CC=CC=C1 FIQOFIRCTOWDOW-BJLQDIEVSA-N 0.000 claims description 2
- 229960002051 trandolapril Drugs 0.000 claims description 2
- 229960004813 trichlormethiazide Drugs 0.000 claims description 2
- 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 claims description 2
- 229940124629 β-receptor antagonist Drugs 0.000 claims description 2
- 230000003276 anti-hypertensive effect Effects 0.000 abstract 3
- 206010020772 Hypertension Diseases 0.000 description 19
- 238000000034 method Methods 0.000 description 11
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 230000001631 hypertensive effect Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 6
- 239000012467 final product Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
- 229920000881 Modified starch Polymers 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 229960000935 dehydrated alcohol Drugs 0.000 description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 5
- 239000008108 microcrystalline cellulose Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 108050000824 Angiotensin II receptor Proteins 0.000 description 2
- 102000008873 Angiotensin II receptor Human genes 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000002532 enzyme inhibitor Substances 0.000 description 2
- 229940125532 enzyme inhibitor Drugs 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- VVQNAFBGAWCMLU-UHFFFAOYSA-N 1h-benzimidazole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1N=CN2 VVQNAFBGAWCMLU-UHFFFAOYSA-N 0.000 description 1
- 101150059573 AGTR1 gene Proteins 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000000400 angiotensin II type 1 receptor blocker Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 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
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 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 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
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- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 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
- 229960004569 indapamide Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
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- 238000011105 stabilization Methods 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a pharmaceutical composition containing azilsartan. The pharmaceutical composition particularly comprises azilsartan and at least one other antihypertensive medicine. The collaborative antihypertensive effect can be effectively played. The pharmaceutical composition for lowering blood pressure, which has a good antihypertensive effect, stable pressure reduction, and good tolerance, is provided.
Description
Technical field
The present invention relates to a kind of hypotensor composition that contains Azilsartan, belong to medical technical field.
Background technology
Hypertension is modal a kind of cardiovascular and cerebrovascular disease in the world at present, it is reported that global hypertensive patient has surpassed 1,000,000,000.The hypertensive patient of China has surpassed 1.6 at present, and hypertensive patient has increasing trend.The hypertensive cause of disease is very complicated, also cannot determine concrete pathogenic factors completely at present, and general hypertensive patient needs treatment throughout one's life to maintain blood pressure stabilization.Follow in addition a series of that hypertension brings to make hypertension become a big factors of harm humans health as the complication of the organs such as heart, brain, kidney, had a strong impact on the mankind's living standard.
Treat clinically at present hypertension drug more, have the various Altace Ramiprils such as calcium antagonist, diuretic, angiotensin-convertion enzyme inhibitor (ACE), angiotensin receptor inhibitor (AT), beta-blocker.But a comprehensive multifactorial process during due to hypertension, the application of these medicines often has its limitation, does not often also reach expected effect in the time for the treatment of clinically.All in the process of clinical use, stable curative effect, the compound hypertension medicine of better tolerance becomes doctor and patient's needs, has also received widely and has paid close attention to.
Azilsartan (Azilsartan), for a kind of novel non-peptide class angiotensin receptor II inhibitor, can optionally block AT1 receptor.Obtain and examine in January, 2012 in Japan, chemical name: 2-ethyoxyl-1-[[2 '-(4,5-dihydro-5-oxo-1,2,4-oxadiazoles-3-yl) biphenyl-4-yl] methyl] benzimidazole-7-carboxylic acid, No. CAS: 147403-03-0.Chemical formula is as follows:
As ABR class medicine of new generation; steadily effectively blood pressure lowering of Azilsartan; improve blood pressure and blood lipoid metabolism; the target organs such as heart and brain kidney are had to protective effect; and it is synthetic not affect Kallidin I degraded and prostaglandin; thereby not causing dry cough and vasodilation, is the important drugs of a class Cardiovarscular.But use separately a hypotensor thing often can not play stable effect in blood pressure lowering, and toleration is poor.Low dose of antihypertensive drugs of combining other is used and tends to reach reasonable effect.
About sartans and calcium antagonist, the existing of the Drug combinations such as diuretic reported widely, and shown clinically reasonable effect at present.The pharmaceutical composition of a Chinese patent CN201110208064.7 Hypertension; CN201110178307.7 Pharmaceutical composition for reducing blood pressure; Medicine hydrochlorothiazide, calcium ion antagonist, angiotensin-convertion enzyme inhibitor that two pieces of patents disclose Azilsartan and blood pressure lowering share and reduce blood pressure.But do not make referrals to the application of this independent chemical composition of Azilsartan in combining with Altace Ramipril.Mono-kind of Chinese patent CN201210072267.2, containing the pharmaceutical composition of Azilsartan, has introduced Azilsartan and has had the effect of combining blood pressure with share of diuretic, has still only related to this diuretic of indapamide, for other medicine, does not explain.
Summary of the invention
During object of the present invention, provide a kind of to treat hypertensive pharmaceutical composition, it is characterized in that being formed by Azilsartan and at least one other Altace Ramipril.Can effectively reduce blood pressure, good stability, can reduce complication and better tolerance.
Technology path
Pharmaceutical composition that can blood pressure lowering, for the one or more combination in Azilsartan and other Altace Ramipril beta-blocker, calcium antagonist, ACE inhibitor, diuretic forms.Beta-blocker is wherein selected from nebivolol, practolol, arotinolol, atenolol, celiprolol, carvedilol, labetalol, bisoprolol.Be preferably in nebivolol, atenolol, arotinolol; Calcium antagonist is wherein selected from nifedipine, amlodipine, Levamlodipine, draws card Horizon, felodipine, nilvadipine, lacidipine, nisoldipine, preferably amlodipine, Levamlodipine, felodipine; ACE inhibitor is wherein selected from alacepril, benazepril, captopril, ceronapril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, lisinopril, ramipril, ramiprilat, perindopril, quinapril, spirapril, temocapril, trandolapril, is preferably enalapril, ramipril, captopril; Diuretic is wherein selected from hydrochlorothiazide, the preferred hydrochlorothiazide of trichlormethiazide.
In this compositions, the unit consumption of Azilsartan is 10-150mg, preferably 20-80mg.
The unit consumption of beta receptor antagonist is:
Nebivolol 1-40mg, preferably 2-10mg
Atenolol 20-500mg, preferably 20-200mg
Arotinolol 1-50mg, preferably 1-20mg
The unit consumption that calcium antagonism connects is:
Amlodipine 1-50mg, preferably 1-20mg
Levamlodipine 1-40mg, preferably 1-20mg
Felodipine 2-60mg, preferably 10-20mg
The consumption of ACE inhibitor is:
Enalapril 1-60mg, preferably 5-20mg
Ramipril 0.5-10mg, preferably 1-2.5mg
Captopril 10-200mg, preferably 10-50mg
The consumption of diuretic is:
Hydrochlorothiazide 20-200mg, preferably 20-100mg
The conventional formulation method that above-mentioned pharmaceutical composition was adopted to this area, is prepared into the oral formulations such as tablet, capsule, granule.
The specific embodiment
Embodiment is only for the present invention is described below, but do not limit the scope of the invention.
Embodiment 1 Azilsartan hydrochlorothiazide tablet
Prescription:
Technique: by Azilsartan, hydrochlorothiazide, microcrystalline Cellulose, pregelatinized Starch and hydroxypropyl methylcellulose mix homogeneously, make binding agent granulate with 5%PVP dehydrated alcohol, 40 ℃ of dry granulate, add magnesium stearate mix tabletting and get final product.
Embodiment 2 Azilsartan nebivolol sheets
Prescription
Technique: by Azilsartan, nebivolol, microcrystalline Cellulose, pregelatinized Starch and hydroxypropyl methylcellulose mix homogeneously, make binding agent granulate with 5%PVP dehydrated alcohol, 40 ℃ of dry granulate, add magnesium stearate mix tabletting and get final product.
Embodiment 3 Azilsartan amlodipines
Prescription
Technique: by Azilsartan, amlodipine, microcrystalline Cellulose, pregelatinized Starch and hydroxypropyl methylcellulose mix homogeneously, make binding agent granulate with 5%PVP dehydrated alcohol, 40 ℃ of dry granulate, add magnesium stearate mix tabletting and get final product.
Embodiment 4 Azilsartan enalapril tablets
Prescription
Technique: by Azilsartan, enalapril, micro-product cellulose, pregelatinized Starch profit hydroxypropyl methylcellulose mix homogeneously, make binding agent granulate with 5%PVP dehydrated alcohol, 40 ℃ of dry granulate, add magnesium stearate mix tabletting and get final product.
Embodiment 5 Azilsartan nebivolol levo-amlodipines
Prescription
Technique: by Azilsartan, nebivolol, Levamlodipine, microcrystalline Cellulose, pregelatinized Starch and hydroxypropyl methylcellulose mix homogeneously, make binding agent granulate with 5%PVP dehydrated alcohol, 40 ℃ of dry granulate, add magnesium stearate mix tabletting and get final product.
Embodiment 6 Azilsartan Ramipril Capsules
Prescription
Technique: Azilsartan, ramipril profit beta-schardinger dextrin-is evenly mixed, add successively microcrystalline Cellulose and micropowder silica gel mixed pelletization encapsulated and get final product.
Embodiment 7 impacts of hypertension agents compositions on spontaneous hypertensive rat blood pressure
Method: get spontaneous hypertensive rat, body weight 3000 ± 20g, after adaptability is fed one week, is divided into animal 8 groups, 10 every group at random.Supply respectively reagent thing, be administered once every day, and gastric infusion is 4 weeks continuously, detects weekly the blood pressure of rat.Rat is fixed in the calorstat of 38 ℃, preheating 10 minutes, detects blood pressure by tail pulses method.
Administration group:
A Azilsartan 5mg/kg
B Azilsartan 2mg/kg+ nebivolol 0.5mg/kg
C Azilsartan 2mg/kg+ Levamlodipine 0.5mg/kg
D Azilsartan 2mg/kg+ hydrochlorothiazide 5mg/kg
E Azilsartan 2mg/kg+ captopril 2mg/kg
F Azilsartan 2mg/kg+ Levamlodipine 0.5mg/kg+ hydrochlorothiazide 5mg/kg
Result of the test:
Hypertension agents compositions is on the impact of spontaneous hypertensive rat blood pressure (n=10)
* compare P < 0.05 with model group, * * and model group be P < 0.01 relatively
By experimental result, can be found out, each administration group shows reasonable blood pressure lowering effect to rat spongtangeous hypertension model.With the simple husky smooth comparison of administration Archie, revealed better effect respectively to compositions medicine group.
Claims (22)
1. a hypotensor composition, is characterized by and contain Azilsartan and at least one other active component.
2. pharmaceutical composition as claimed in claim 1, wherein at least one other active component is Altace Ramipril.
3. pharmaceutical composition as claimed in claim 2, Altace Ramipril is wherein selected from one or more in beta-blocker, calcium antagonist, ACE inhibitor, diuretic.
4. pharmaceutical composition as claimed in claim 2, Altace Ramipril is wherein beta-blocker.
5. pharmaceutical composition as claimed in claim 4, beta-blocker is wherein selected from nebivolol, practolol, arotinolol, atenolol, celiprolol, carvedilol, labetalol, bisoprolol.
6. pharmaceutical composition as claimed in claim 5, beta-blocker is wherein in nebivolol, atenolol, arotinolol.
7. pharmaceutical composition as claimed in claim 2, Altace Ramipril is wherein calcium antagonist.
8. pharmaceutical composition as claimed in claim 6, calcium antagonist is wherein selected from nifedipine, amlodipine, Levamlodipine, draws card Horizon, felodipine, nilvadipine, lacidipine, nisoldipine.
9. pharmaceutical composition as claimed in claim 8, calcium antagonist is wherein amlodipine, Levamlodipine, felodipine.
10. pharmaceutical composition as claimed in claim 2, Altace Ramipril is wherein ACE inhibitor.
11. pharmaceutical composition as claimed in claim 8, ACE inhibitor is wherein selected from alacepril, benazepril, captopril, ceronapril, cilazapril, delapril, enalapril, enalaprilat, fosinopril, lisinopril, ramipril, ramiprilat, perindopril, quinapril, spirapril, temocapril, trandolapril.
12. pharmaceutical compositions as claimed in claim 11, ACE inhibitor be wherein enalapril, ramipril, captopril and.
13. pharmaceutical compositions as claimed in claim 2, Altace Ramipril is wherein diuretic.
14. pharmaceutical compositions as claimed in claim 10, diuretic is wherein selected from hydrochlorothiazide, trichlormethiazide.
15. pharmaceutical compositions as claimed in claim 14, diuretic is wherein hydrochlorothiazide.
16. pharmaceutical compositions as claimed in claim 2, wherein Altace Ramipril is Levamlodipine, hydrochlorothiazide mixture or nebivolol, Levamlodipine mixture.
17. pharmaceutical compositions as claimed in claim 1, the unit consumption that it is characterized in that Azilsartan is 10-150mg, preferably 20-80mg.
The thin compound of 18. medicine as claimed in claim 3, is characterized in that wherein the unit consumption of beta receptor antagonist is nebivolol 1-40mg, preferably 2-10mg; Atenolol 20-500mg, preferably 20-200mg; Arotinolol 1-50mg, preferably 1-20mg.
19. pharmaceutical compositions as claimed in claim 3, is characterized in that the unit consumption that calcium antagonism connects is amlodipine 1-50mg, preferably 1-20mg; Levamlodipine 1-40mg, preferably 1-20mg; Felodipine 2-60mg, preferably 10-20mg.
20. pharmaceutical composition as claimed in claim 3, is characterized in that the consumption of ACE inhibitor is: enalapril 1-60mg, preferably 5-20mg; Ramipril 0.5-10mg, preferably 1-2.5mg; Captopril 10-200mg, preferably 10-50mg.
21. pharmaceutical compositions as claimed in claim 3, the consumption that it is characterized in that diuretic is hydrochlorothiazide 20-200mg, preferably 20-100mg.
22. pharmaceutical compositions claimed in claim 1, is characterized in that making oral formulations and comprise tablet, capsule and granule.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104436155A (en) * | 2014-12-23 | 2015-03-25 | 南京先宇科技有限公司 | Pharmaceutical composition containing levamlodipine and perindopril and preparation method |
| CN104644632A (en) * | 2015-01-27 | 2015-05-27 | 美吉斯制药（厦门）有限公司 | Orally taken tablet containing Azilsartan and benzenesulfonate amlodipine and preparation method thereof |
| CN105853418A (en) * | 2016-05-23 | 2016-08-17 | 上海麦步医药科技有限公司 | Composition containing levorotatory amlodipine and azilsartan |
| CN106668016A (en) * | 2015-11-11 | 2017-05-17 | 江苏先声药业有限公司 | Solid preparation of azilsartan and levamlodpine besylate composition and preparation method of solid preparation |
| CN107007812A (en) * | 2017-04-05 | 2017-08-04 | 江苏大学 | A kind of method for extending captopril hypotensive efficacy time |
| WO2024055984A1 (en) * | 2022-09-14 | 2024-03-21 | 上海云晟研新生物科技有限公司 | Nebivolol and amlodipine composition, preparation method therefor, and use thereof |
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| CN102225203A (en) * | 2011-06-29 | 2011-10-26 | 北京阜康仁生物制药科技有限公司 | Pharmaceutical composition used for lowering blood pressure |
| CN102342944A (en) * | 2011-07-14 | 2012-02-08 | 丁尧 | Medicament composition for treating hypertension |
| CN102580097A (en) * | 2012-03-16 | 2012-07-18 | 江苏先声药物研究有限公司 | Medicinal composition containing azilsartan |
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| CN102225203A (en) * | 2011-06-29 | 2011-10-26 | 北京阜康仁生物制药科技有限公司 | Pharmaceutical composition used for lowering blood pressure |
| CN102342944A (en) * | 2011-07-14 | 2012-02-08 | 丁尧 | Medicament composition for treating hypertension |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104436155A (en) * | 2014-12-23 | 2015-03-25 | 南京先宇科技有限公司 | Pharmaceutical composition containing levamlodipine and perindopril and preparation method |
| CN104644632A (en) * | 2015-01-27 | 2015-05-27 | 美吉斯制药（厦门）有限公司 | Orally taken tablet containing Azilsartan and benzenesulfonate amlodipine and preparation method thereof |
| CN106668016A (en) * | 2015-11-11 | 2017-05-17 | 江苏先声药业有限公司 | Solid preparation of azilsartan and levamlodpine besylate composition and preparation method of solid preparation |
| CN106668016B (en) * | 2015-11-11 | 2020-06-23 | 江苏先声药业有限公司 | Solid preparation of azilsartan and amlodipine besylate composition and preparation method thereof |
| CN105853418A (en) * | 2016-05-23 | 2016-08-17 | 上海麦步医药科技有限公司 | Composition containing levorotatory amlodipine and azilsartan |
| CN107007812A (en) * | 2017-04-05 | 2017-08-04 | 江苏大学 | A kind of method for extending captopril hypotensive efficacy time |
| WO2024055984A1 (en) * | 2022-09-14 | 2024-03-21 | 上海云晟研新生物科技有限公司 | Nebivolol and amlodipine composition, preparation method therefor, and use thereof |
| CN118043047A (en) * | 2022-09-14 | 2024-05-14 | 上海云晟研新生物科技有限公司 | Nebivolol and amlodipine composition, and preparation method and application thereof |
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