CN1493284A - Composite blood pressure reducing agent containing indapamide and angiotensin II acceptor antagonist - Google Patents
Composite blood pressure reducing agent containing indapamide and angiotensin II acceptor antagonist Download PDFInfo
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Abstract
A compound antihypertensive medicine contains indapamide, the augiotonin II receptor antagon chosen from irbesartan, candesantan, tilmisartan, etc. and pharmacologically receptable carrier. Its advantages are high effect and low by-effect.
Description
Technical field
The present invention relates to a kind of novel composite antihypertensive preparation, be specifically related to a kind of composite antihypertensive preparation that contains indopamide and angiotensin ii receptor antagonist.
Background technology
In recent years, most large-scale internal authority hypertension clinical trials and the hypertension therapeutic guide of working out according to evidence-based medicine EBM show, strengthen the blood pressure lowering dynamics, actively, make hyperpietic's blood pressure reduce to 130/85 millimetres of mercury following (it is following that the best should be reduced to 120/80 millimetres of mercury) enduringly, the target organ damages such as heart and brain kidney that cause of alleviating hypertension effectively, reduce or the postponement apoplexy, coronary heart disease, angina pectoris, myocardial infarction, renal failure, atherosclerosis, the generation of complication such as aneurysm, reduce the cardiovascular and cerebrovascular vessel incident rate, mortality rate and disability rate, improve patients ' life quality, prolong patient's life-span.
Studies show that, in order to reach actively, strengthen the purpose of blood pressure lowering, two or more antihypertensive drugs [list of references: hypertension optimal treatment research (HOT Study) Lancet1998 of the needs of patients coupling of 70-100%; 351:1755-1762; Resisting hypertension and blood fat reducing prevention myocardial infarction research (ALLHAT Study) 2002, JAMA 288,2981-97, Britain's diabetes perspective study (UK PDS Study 1993), N EngJ Med, 329,977-86].Drug combination not only because the addition or the synergism of medicine can obviously improve antihypertensive effect, but also because after the drug dose minimizing, reduced side effects of pharmaceutical drugs, has improved safety and patient's compliance.Most literature proves that the reasonable associating of two kinds of antihypertensive drug can also be cancelled each other two kinds and be united the detrimental effect that composition exists separately.Therefore the current domestic and international consistent scheme of combination drug therapy treatment hyperpietic who comprises compound preparation that recommends to adopt.
The composite antihypertensive preparation of the dosage fixed mixing ratio of China's production at present comprises:
FUFANG JIANGYA PIAN (hydrochlorothiazide+reserpine+nepresol etc.),
Zhenju Jiangya Tablet (hydrochlorothiazide+clonidine etc.),
FUFANG LUOBUMA PIAN (hydrochlorothiazide+guanethidine+nepresol etc.) and
Hypotensor No 0 (Triamterene+Reserpine+Hydrochlorothiazide+Dihydralazine+Chlordiazepoxide) (hydrochlorothiazide+reserpine+dihydralazine etc.) etc.
These preparations all are the products before and after the initial stage sixties, do not produce new composite antihypertensive preparation thereafter over more than 40 year basically again.
For many years, a large amount of clinical practices prove, compare with single agent medication, adopt that fixed mixing ratio type composite antihypertensive preparation curative effect improves relatively, side effect minimizing, taking convenience, price be relatively cheap, has good practicality, by numerous doctors, especially doctor of basic unit and numerous hyperpietics are glad applies.
It should be noted that with the U.S. to be example, produced Lotrel (amlodipine+benazepril) in recent years, Lexxel (felodipine+enalapril), Tarka (Qu Lundao Puli+isoptin), Lotensin HCT (benazepril+hydrochlorothiazide), Capozide (captopril+hydrochlorothiazide), Vaseretic (enalapril+hydrochlorothiazide), Prinzide (Lisinopril+hydrochlorothiazide), Uniretic (moexipril+hydrochlorothiazide), Accuretic (quinapril+hydrochlorothiazide), Atacand HCT (Candesartan+hydrochlorothiazide), TevetenHCT (eprosartan+hydrochlorothiazide), Avalid (irbesartan+hydrochlorothiazide), Hyzaar (losartan+hydrochlorothiazide), Miicardis HCT (telmisartan+hydrochlorothiazide), Diovan HCT (Valsartan+hydrochlorothiazide), Tenoretic (atenolol+chlortalidone), Ziac (bisoprolol+hydrochlorothiazide), Inderid (Propranolol+hydrochlorothiazide), Lopressor HCT (Mei Tuo feels at ease+hydrochlorothiazide), Corzide (nadolol+bendroflumethiazide), Timolidedoril (methyldopa+hydrochlorothiazide), Diupes (reserpine+chlorothiazide), Hydripres (reserpine+hydrochlorothiazide), Moduretic (amiloride+hydrochlorothiazide), Aldactone (spironolactone+hydrochlorothiazide), basudin (Diazide), the composite antihypertensive preparation listing of Maxzide 27 kinds of dosage fixed mixing ratio such as (phenalgin are talked endlessly and decided+hydrochlorothiazide), and extensively be applied to clinical.Recently, compound preparation Hyzaar (losartan 50mg+ hydrochlorothiazide 12.5mg/ sheet) (production of Hangzhou Mo Shadong pharmaceutical Co. Ltd) has entered China market.Also have Compound Furosemide (furosemide 20mg+ amiloride 2.5mg) (production of people's livelihood Pharmaceutical) and two kinds of preparations of Wudu power (hydrochlorothiazide 25mg+ amiloride 2.5mg) (sky, Jiangsu standing grain pharmaceutical manufacturing) on the China market.
Because composite antihypertensive preparation is actually a kind of important supplement and the extension of drug combination principle and personalized medicine principle.Therefore, China presses for the new multiple composite antihypertensive preparation that exploitation is treated, cost is low, side effect is little in this area.
Summary of the invention
The purpose of this invention is to provide a kind of new composite antihypertensive preparation, it has the high advantage of good effect, few side effects and cost performance.
In a first aspect of the present invention, a kind of composite antihypertensive preparation is provided, each preparation includes 0.15-2.5mg diuretic indopamide (Indapamide), 2-800mg angiotensin ii receptor antagonist and pharmaceutically acceptable carrier, described angiotensin ii receptor antagonist is selected from losartan (Losartan), Valsartan (Valsartan), irbesartan (Irbesartan), Candesartan (Candesartan), telmisartan (Telmisartan), eprosartan (Eprosartan), Mi Shatan (Olmesartan), or its mixture is in another preference, and described angiotensin ii receptor antagonist is a losartan, Valsartan, or irbesartan.More preferably, described angiotensin ii receptor antagonist is a losartan.
In another preference, in composite antihypertensive preparation, the content of described indopamide is 0.5-2mg, more preferably is 0.75-1.5mg.
In another preference, in composite antihypertensive preparation, the content of described angiotensin ii receptor antagonist is 5-400mg, more preferably is 10-200mg.
In another preference, described indopamide can be different with the angiotensin ii receptor antagonist of selecting for use with the content ratio of angiotensin ii receptor antagonist, are specially 1: 1-1: 800, be preferably 1: 1-1: 400, be more preferred from 1: 1-1: 200, the best is 1: 1-1: 20.
In another preference, the dosage form of described composite antihypertensive preparation is tablet or capsule, spacetabs type or non-spacetabs type.
The specific embodiment
The present inventor finds that through clinical experiment in recent years and practice diuretic indopamide and angiotensin ii receptor antagonist coupling have the obvious synergistic effect, can improve the generation of efficacy of antihypertensive treatment, minimizing side effect.Based on above-mentioned discovery, the invention provides a kind of new composite antihypertensive preparation, it contains the angiotensin ii receptor antagonist of the diuretic indopamide and the effectively collaborative dosage (as 2-800mg) of effectively collaborative dosage (as 0.15-2.5mg).
In the present invention, used diuretic is an indopamide.Diuretic is the most basic medicine of hypertension therapeutic.Indopamide is that diuretic has certain calcium antagonist effect again, by alleviating the reaction of blood vessel wall for sodium ion, suppress the calcium channel of cells of vascular wall and slightly suppress the kidney distal tubule relaxing smooth muscle, blood vessel dilating are played in the absorption again of sodium, hypotensive effects such as diuresis row sodium.Indopamide also has the synthetic of promotion prostacyclin I2 and E2, thereby plays coronary artery dilator and peripheral vascular effect.
Clinical practice proves, the diuretic indopamide is offset the effect that the activation of renin-angiotensin system can be generated by the inhibition angiotensin that angiotensin ii receptor antagonist (as losartan, Valsartan, irbesartan, Candesartan, telmisartan, eprosartan, Mi Shatan etc.) are had.The stagnant potassium effect of angiotensin ii receptor antagonist can also be offset the hypokalemia that low dose of diuretic indopamide may cause, thereby helps reducing side effect, increases safety.
Numerous clinical trial of the present invention proves, the diuretic indopamide is applicable to low renin hypertension, and angiotensin ii receptor antagonist is all applicable for low renin and high renin hypertension patient, The combined, can play synergism, improve efficacy of antihypertensive treatment.
Can be used for angiotensin ii receptor antagonist of the present invention has no particular limits.The example of representational angiotensin ii receptor antagonist includes, but is not limited to: losartan, Valsartan, irbesartan, Candesartan, telmisartan, eprosartan, Mi Shatan or its mixture.More preferably, described angiotensin ii receptor antagonist is selected from losartan, Valsartan or irbesartan.More preferably, be selected from losartan.
Angiotensin ii receptor antagonist in the novel antihypertensive formulation of compound recipe of the present invention, by suppressing the generation of Angiotensin II in circulation and the tissue, the expansion small artery alleviates cardiac afterload, plays effective antihypertensive function.Compare with angiotensin converting enzyme inhibitor, it is more complete that angiotensin ii receptor antagonist has the retardance angiotensin, advantages such as the obvious minimizing of dry cough side effect.
Described losartan; Valsartan; irbesartan; Candesartan; telmisartan; eprosartan; angiotensin ii receptor antagonist such as Mi Shatan also have good neuroendocrine effect; such as alleviating rational fibrosis of cardiomyopathy and vascular smooth muscle hypertrophy; improve the pathologic reconstruct of heart and blood vessel; reverse ventricular hypertrophy; improve insulin sensitivity, resist myocardial ischemia; improve blood vessel inner skin cell function; stop the atherosis formation and development of artery; prevent that atherosclerotic plaque from breaking; advantageous effects such as protection cardiorenal function and protection target organ and blood vessel.
Described diuretic indopamide and angiotensin ii receptor antagonist such as losartan, Valsartan, irbesartan, Candesartan, telmisartan, eprosartan, Mi Shatan etc. meet one of first-selected best antihypertensive drugs that up-to-date hypertension therapeutic guide (JNC 7) that Chinese hypertension prevention and control guide, the state-run commune hospital of the World Health Organization (WHO)/International Society of Hypertension (WHO/ISH) and U.S. cardiopulmonary Blood Research Institute hypertension joint committee deliver on May 14th, 2003 recommends.
In composite antihypertensive preparation of the present invention, the content of diuretic indopamide is 0.15-2.5mg, and the content of angiotensin ii receptor antagonist is 2-800mg.Preferably, the content of indopamide is 0.5-2mg, and the content of angiotensin ii receptor antagonist is 5-400mg.More preferably, the content of indopamide is 0.75-1.5mg, and the content of angiotensin ii receptor antagonist is 10-200mg.
In the present invention, the content of described diuretic indopamide and angiotensin ii receptor antagonist is specially 1: 1-1 than different with the angiotensin ii receptor antagonist of selecting for use: 800, be preferably 1: 1-1: 400, be more preferred from 1: 1-1: 200, the best is 1: 1-1: 20.
The dosage form and the preparation method of composite antihypertensive preparation of the present invention are not particularly limited, and the conventional general method for making in available this area is made various dosage forms such as tablet, capsule, granule, slow releasing agent, injection.
Preparation of the present invention is applicable to various hypertension, is particularly useful for senile hypertension, systolic hypertension and merges edema, obesity, diabetes, impaired glucose tolerance, blood insulin opposing, Microalbuminuria, slight renal function injury, left ventricular hypertrophy or hypertrophic cardiomyopathy, relaxing period or/and hypertension patients such as systole cardiac insufficiency (acute and chronic heart failure), atherosclerosis, aneurysm or other organic heart diseasies.
Compound preparation of the present invention has been applicable to uses the angiotensin converting enzyme inhibitor indication, and can not tolerate the patient of angiotensin converting enzyme inhibitor.
Compound preparation of the present invention also is applicable to the various organic heart disease patient of treatment normotensive acute or chronic cardiac insufficiency and congestive heart failure and with the myocardial infarction patient of cardiac insufficiency.
In addition, preparation of the present invention can be taken once or twice every day, takes once the next day of perhaps in the slow release mode.Preferred mode is to take medicine once every day, adheres to because be convenient to patient like this, thereby significantly improves the compliance that patient takes medicine.Took every day twice o'clock, generally, should to be lower than the general common dose of the every day of (or only a few case equal or a little higher than) each single medicine (be that indopamide is less than (or being equal to or slightly greater than) 2.5mg, angiotensin ii receptor antagonist every day and is less than (or equal or a little higher than) 2-800mg every day to the accumulated dose of using thumping majority case every day.
Preparation of the present invention also can be applicable to through non-medicine measures such as positive change bad life style and still fail satisfactorily controlling blood pressure more than 6 months to the hypertension patient in early stage of ideal value to reduce the dosage mode, and promptly systolic pressure continues to continue patient at the 80-89 millimetres of mercury at 120-139 millimetres of mercury or diastolic pressure.
Hypertension is a kind of multi-factor disease, often needs more than one antihypertensive drugs ability blood pressure lowerings up to standard, and generally all needs lifelong monitoring, takes medicine for a long time.Novel compound antihypertensive formulation of the present invention has utilized the synergism between the medicine, under the situation of using less medicament, improve antihypertensive effect, reduced side effect, had good cost performance, improved patient's compliance, be convenient in a large amount of crowds, promote the popularization use.
Describe the present invention in detail below in conjunction with embodiment, these embodiment are presented for purposes of illustration, do not limit the scope of the invention.
Embodiment 1-6
The preparation of composite antihypertensive preparation
The indopamide that uses is indapamide, and Li Sheng pharmaceutical factory in Tianjin produces; Used losartan is a losartan, Hangzhou Mo Shadong pharmaceutical manufacturing.
Use the formulation of the conventional method according to the form below 1 in the pharmaceuticals industry to become capsule.
Table 1
| Embodiment | The content of indopamide (mg/ capsule) | The content of losartan (mg/ capsule) |
| ????1 | ????0.75 | ????12.5 |
| ????2 | ????1 | ????25 |
| ????3 | ????1.25 | ????37.5 |
| ????4 | ????1.5 | ????50 |
| ????5 | ????1.75 | ????62.5 |
| ????6 | ????2.25 | ????75 |
Embodiment 7-12
The preparation of composite antihypertensive preparation
The indopamide that uses is indapamide, and Li Sheng pharmaceutical factory in Tianjin produces; Used Valsartan is a DAIWEN, and Beijing Novartis is produced.
Use the formulation of the conventional method according to the form below 2 in the pharmaceuticals industry to become capsule.
Table 2
| Embodiment | The content of indopamide (mg/ capsule) | The content of Valsartan (mg/ capsule) |
| ????7 | ????0.75 | ????100 |
| ????8 | ????1 | ????120 |
| ????9 | ????1.25 | ????140 |
| ????10 | ????1.5 | ????160 |
| ????11 | ????1.75 | ????200 |
| ????12 | ????2.25 | ????220 |
Embodiment 13-18
The preparation of composite antihypertensive preparation
The indopamide that uses is indapamide, and Li Sheng pharmaceutical factory in Tianjin produces; Used irbesartan is that Hangzhou Sano-Synth labo people's livelihood drugmaker produces.
Use the formulation of the conventional method according to the form below 3 in the pharmaceuticals industry to become capsule.
Table 3
| Embodiment | The content of indopamide (mg/ capsule) | The content of irbesartan (mg/ capsule) |
| ????13 | ????0.75 | ????100 |
| ????14 | ????1 | ????125 |
| ????15 | ????1.25 | ????150 |
| ????16 | ????1.5 | ????175 |
| ????17 | ????1.75 | ????200 |
| ????18 | ????2.25 | ????225 |
Embodiment 19
The administering drug combinations of indopamide and angiotensin ii receptor antagonist-losartan
To one group of 111 routine primary hypertension patient, be divided into indopamide group, losartan group and indopamide associating losartan compound preparation group at random, schedule to last the observation in average 8 weeks, the results are shown in following table 4.
Table 4 indopamide and losartan compound preparation group and matched group indopamide group and losartan group
Antihypertensive therapy relatively
| Group | Mean dose mg | Blood pressure mmHg | Therapeutic outcome | |||
| Before the treatment | After the treatment | Compliance rate % | Effective percentage % | Inefficiency % | ||
| Indopamide group n=36 | ??3.5±1.1 | ??160.3±17.8/ ??91.2±5.8 | ????140.7±14.8/ ????82.3±4.3 | ??43.3 | ??70.2 | ??29.8 |
| Losartan group n=38 | ??96.8±21.3 | ??160.8±16.3/ ??91.9±5.7 | ????142.4±15.6/ ????83.2±7.4 | ??41.2 | ??68.8 | ??31.2 |
| Indopamide associating losartan compound preparation group n=37 | ??1.8±0.4 ??54±11.6 | ??161.4±18.3/ ??90.2±6.8 | ????130.6±16.1/ ????82.1±6.3 | ??64.8 | ??79.4 | ??20.6 |
| The P value | ??1∶2∶3＞0.05 | ????1∶2＞0.05 ????1∶3＜0.01 ????2∶3＜0.01 | ??1∶2＞0.05 ??1∶3＜0.01 ??2∶3＜0.01 | ??1∶2＞0.05 ??1∶3＜0.05 ??2∶3＜0.05 | ??1∶2＞0.05 ??1∶3＜0.05 ??2∶3＜0.05 | |
Annotate:
(1) indopamide group therapeutic dose: each 2.5～5 milligrams, once a day;
Losartan group therapeutic dose: each 25～100 milligrams of every days 1-2 time:
Compound preparation group therapeutic dose: each capsule includes indopamide 1.25mg ± losartan
37.5mg, every day 1-2 time, each 1 capsule.
(2) blood pressure is up to standard: refer to treat the bleeding from anus pressure drop and be low to moderate≤135/85mmHg.
(3) blood pressure lowering is effective: refer to treat preceding reduction 〉=20mmHg of after-contraction pressure ratio treatment or diastolic pressure reduction 〉=10mmHg; Or systolic pressure reduction 〉=10mmHg while diastolic pressure reduction 〉=5mmHg.
(4) the P value refers to t test value between two groups.
The result proves:
The blood pressure of single medicine group indopamide group and the losartan group 160.3 ± 17.8/91.2 ± 5.8mmHg160.8 ± 16.3/91.9 ± 5.7mmHg before treatment is respectively reduced to 140.7 ± 14.8/82.3 ± 4.3mmHg, 142.4 ± 15.6/83.2 ± 7.4mmHg (P value＜0.001).
Unite losartan compound preparation group than low dosage than the indopamide of low dosage: the 161.4 ± 18.3/90.2 ± 6.8mmHg of blood pressure before treatment reduces to 130.6 ± 16.1/82.1 ± 6.3mmHg (P value＜0.0001).
Significant difference between single medicine group indopamide group and indopamide group and the compound preparation group blood pressure lowering amplitude (P all＜0.01), blood pressure compliance rate, the effective percentage of compound preparation group treatment group are 64.8% and 79.4%, and (P all＜0.05-0.01) obviously to be better than single therapy group indopamide group and losartan group; Side effect incidence rate 3.5% also obviously is less than single therapy group (P all＜0.05) (table 5)
Table 5 indapamide group, losartan group and indapamide associating losartan compound preparation group
The antihypertensive therapy side effect relatively
| Group | Headache | Dizzy | Weak | Dry cough | Polyuria | Xerostomia | Hypokalemia | Potassemia | Blood glucose increases | Total incidence rate % |
| Indopamide group n=36 | ??0 | ??0 | ??1 | ??0 | ??1 | ??1 | ??1 | ??0 | ??1 | ??5.5 |
| Losartan group n=38 | ??1 | ??0 | ??0 | ??0 | ??0 | ??-0 | ??0 | ??1 | ??0 | ??5.2 |
| Indopamide associating losartan group n=37 | ??1 | ??1 | ??0 | ??0 | ??0 | ??0 | ??0 | ??0 | ??0 | ??3.5 |
| The P value | ??1∶2＞0.05 ??1∶3＜0.05 ??2∶3＜0.05 |
Embodiment 20
The administering drug combinations of indopamide and angiotensin ii receptor antagonist-Valsartan
One group of 91 routine primary hypertension patient is divided into the observation that indopamide group, Valsartan group and indopamide associating Valsartan compound preparation group schedule to last average 12 weeks at random, the results are shown in following table 6.
Table 6 indopamide and Valsartan compound preparation group and matched group indopamide group+Valsartan compound preparation
The group antihypertensive therapy relatively
| Group | Mean dose mg | Blood pressure mmHg | Therapeutic outcome | |||
| Before the treatment | After the treatment | Compliance rate % | Effective percentage % | Inefficiency % | ||
| Indopamide group n=30 | ??3.3±0.6 | 161.2±15.7/ 90.7±4.9 | ?141.9±13.6/8 ?3.2±5.1 | ??40.8 | ??69.9 | ??30.1 |
| Valsartan group n=30 | ??228.8±62.3 | 160.8±16.3/ 91.9±5.7 | ?142.4±15.6/ ?83.2±7.4 | ??41.2 | ??66.7 | ??33.3 |
| Indopamide associating Valsartan compound preparation group n=31 | ??1.9±0.3 ??182±28.8 | 62.1±19.3/9 1.2±5.9 | ?128.4±17.2/8 ?4.1±7.2 | ??60.6 | ??84.2 | ??15.8 |
| The P value | 1∶2∶3＞0.05 | ?1∶2＞0.05 ?1∶3＜0.01 ?2∶3＜0.01 | ??1∶2＞0.05 ??1∶3＜0.01 ??2∶3＜0.01 | ??1∶2＞0.05 ??1∶3＜0.01 ??2∶3＜0.01 | ??1∶2＞0.05 ??1∶3＜0.01 ??2∶3＜0.01 | |
Annotate:
(1) indopamide group therapeutic dose: each 2.5～5 milligrams, once a day;
Valsartan group therapeutic dose: each 80～320 milligrams of every days 1 time:
Compound preparation group therapeutic dose: each capsule includes indopamide 1.25mg+ Valsartan
120mg, each 1-2 capsule, every day 1 time.
(2) blood pressure is up to standard: refer to treat the bleeding from anus pressure drop and be low to moderate≤135/85mmHg.
(3) blood pressure lowering is effective: refer to treat preceding reduction 〉=20mmHg of after-contraction pressure ratio treatment or diastolic pressure reduction 〉=10mmHg; Or systolic pressure reduction 〉=10mmHg while diastolic pressure reduction 〉=5mmHg.
(4) the P value refers to t test value between two groups.
The result shows:
The blood pressure of single medicine group indopamide group and Valsartan group 161.2 ± 15.7/90.7 ± 4.9mmHg, the 160.8 ± 16.3/91.9 ± 5.7mmHg before treatment is respectively reduced to 141.9 ± 13.6/83.2 ± 5.1mmHg, 142.4 ± 15.6/83.2 ± 7.4mmHg (P value＜0.001).
Unite Valsartan compound preparation group than low dosage than the indopamide of low dosage: the 162.1 ± 19.3/91.2 ± 5.9mmHg of blood pressure before treatment reduces to 128.4 ± 17.2/84.1 ± 7.2mmHg (P value＜0.0001).
Significant difference between single medicine group indopamide group and indopamide group and the compound preparation group blood pressure lowering amplitude (P all＜0.01), blood pressure compliance rate, the effective percentage of compound preparation group treatment group are 60.6% and 84.2%, obviously are better than single therapy group indopamide group and losartan group (P all＜0.01); Side effect incidence rate 4% also obviously is less than single therapy group (P all＜0.05).
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read content described above of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (10)
1. composite antihypertensive preparation, it is characterized in that, each preparation includes 0.15-2.5mg diuretic indopamide, 2-800mg angiotensin ii receptor antagonist and pharmaceutically acceptable carrier, and described angiotensin ii receptor antagonist is selected from losartan, Valsartan, irbesartan, Candesartan, telmisartan, eprosartan, Mi Shatan or its mixture.
2. composite antihypertensive preparation as claimed in claim 1 is characterized in that, described angiotensin ii receptor antagonist is losartan, Valsartan or irbesartan.
3. composite antihypertensive preparation as claimed in claim 1 is characterized in that, described angiotensin ii receptor antagonist is a losartan.
4. composite antihypertensive preparation as claimed in claim 1 is characterized in that, the content of described indopamide is 0.5-2mg.
5. composite antihypertensive preparation as claimed in claim 1 is characterized in that, the content of described indopamide is 0.75-1.5mg.
6. composite antihypertensive preparation as claimed in claim 1 is characterized in that, the content of described angiotensin ii receptor antagonist is 5-400mg.
7. composite antihypertensive preparation as claimed in claim 1 is characterized in that, the content of described angiotensin ii receptor antagonist is 10-200mg.
8. composite antihypertensive preparation as claimed in claim 1 is characterized in that, described indopamide is 1 with the content ratio of angiotensin ii receptor antagonist: 1-1: 800.
9. composite antihypertensive preparation as claimed in claim 1 is characterized in that, described indopamide is 1 with the content ratio of angiotensin ii receptor antagonist: 1-1: 400, be preferably 1: 1-1: 20.
10. composite antihypertensive preparation as claimed in claim 1 is characterized in that, the dosage form of described preparation is tablet or capsule, spacetabs type or non-spacetabs type.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100384416C (en) * | 2006-03-20 | 2008-04-30 | 杨军 | Medicinal composition for treating cerebrovascular disease |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100384416C (en) * | 2006-03-20 | 2008-04-30 | 杨军 | Medicinal composition for treating cerebrovascular disease |
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