CN1562369A - Combination of medication for curing high blood pressure - Google Patents
Combination of medication for curing high blood pressure Download PDFInfo
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- CN1562369A CN1562369A CN 200410023771 CN200410023771A CN1562369A CN 1562369 A CN1562369 A CN 1562369A CN 200410023771 CN200410023771 CN 200410023771 CN 200410023771 A CN200410023771 A CN 200410023771A CN 1562369 A CN1562369 A CN 1562369A
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Abstract
A composite medicine for treating hypertension is prepared from Ca-ion antagon, beta-1-receptor paralyser, diuretic, aldosterone antagon, angiotonin II receptor antagon, and auxiliaries.
Description
One, technical field
The invention belongs to a kind of medicine compounded technology, can be used for treating hypertension, specifically a kind of can the counteracting and the minimizing side effects of pharmaceutical drugs effectively protected the hypertensive pharmaceutical composition of treatment of human organ.
Two, technical background
Hypertensive paathogenic factor is more.The folk prescription medicament only can be to it some or certain several factor pointed (effectiveness), and can not be pointed to all paathogenic factors, therefore, can not effectively control its blood pressure to all hyperpietics, be forced to escalated dose, its therapeutical effect that brings high blood pressure down can be strengthened, maybe can be with the near desirable level of blood pressure, its dosage correlation side effect this moment then can obviously increase, even reaches the degree that can not tolerate, and compliance reduces and causes abrupt antihypertensive therapy to be failed.
Adopt compound preparation can overcome this class deficiency of folk prescription medicament.The sixties abroad and the compound preparation of the domestic priority development seventies is existing multiple uses clinically, because of its composition is backward relatively, has some defectives, has occurred by the alternate trend of new drug at present.
Three, summary of the invention
The purpose of this invention is to provide the hypertensive pharmaceutical composition of a kind of treatment, it is less, safe and effective, with low cost by mechanism of action difference, side effect, vitals are made up of the pharmaceutical compositions of protective effect certainly.Each composition is combined by a certain percentage, and its therapeutical effect is collaborative, and ill effect is cancelled out each other, and subject range is wider, cost-effective, taking convenience.
First advantage of the present invention is; in this compound preparation; the collocation of each active ingredient never is the simple mixing of multiple medicine; but at the different factors and the mechanism of hypertension and concurrent pathological changes thereof morbidity; the medicine that selection has corresponding pharmacological mechanism cooperatively interacts; thereby the different onset link, the different loci that act on hypertension and concurrent pathological changes thereof respectively produce synergism; therapeutical effect is strong and comprehensive; can make unusual elevated blood pressure return to desirable level; make body realize new physiological equilibrium, important organ is protected.
The 3rd advantage of the present invention is in compound preparation, and the quantitative collocation of each active ingredient can make inherent side effect separately cancel out each other, and covers the shortage mutually, and its comprehensive side effect can be minimized, even does not have institute and discover, and is difficult to cause harm.
The 3rd advantage of the present invention is: the usual amounts when the consumption of this each active ingredient of compound preparation all uses less than its folk prescription, its inherent dosage related side effects therefore and further reduces, reduce even disappearance, its treatment cost is able to remarkable reduction, improve the compliance of Drug therapy from economic angle, improved the success rate of hypertension therapeutic.
Above-mentioned advantage is based on following mechanism realization:
The hypertension paathogenic factor has multiple, and pathogenesis is not illustrated as yet fully.Now generally acknowledged, the cardiovascular dyskinesia be hypertension development takes place must be by link, this unusual main be to show as cardiac output to increase, peripheral vascular resistance increases, and the large artery trunks compliance reduces, wherein cardiac output and peripheral vascular resistance are that main, the adjustable link of development takes place hypertension unusually, and present antihypertensive nearly all plays a role on this link by a certain regulatory mechanism.
At present, the chemical synthetic drug of treatment hypertension can be divided into six big classes substantially: diuretic, β1-Shou Ti blocker, calcium ion antagonist, angiotensin, converting enzyme inhibitor, Angiotensin II, receptor antagonist α 1-adrenoceptor blocker.Their blood pressure lowering mechanism has nothing in common with each other, but finally all shows as angiocardiokinetic optimum adjusting.Its untoward reaction (side effect) is also different different because of its blood pressure lowering mechanism.
One) diuretic (being the diuretic antihypertensive medicine) is one of putative basic hypotensor early.Nineteen fifty-seven comes out, and the sixties is external just with hydrochlorothiazide and reserpine, and Aiselazine three medicines are combined as compound depressor and are used for clinical.Think that at present this medicine is by diuresis row sodium, reduce the sensitivity of blood vessel wall, promptly reduce vascular resistance and realize blood pressure lowering effect, so it is particularly useful for sodium sensitivity hyperpietic and with the hyperpietic of retention of sodium and water vaso-excitor material.Medicine commonly used is hydrochlorothiazide (Hydrochlorothiazide) Indapamide etc.Owing to also arrange potassium in the time of diuretic row sodium, reduce admittedly can cause blood potassium, also there is report to claim diuretic might raise blood glucose, blood fat and blood uric acid.Even now advocates still that up to the U.S. in 1997 diuretic is the first line hypotensor.
Two) the β1-Shou Ti blocker also is one of putative basic hypotensor early.This medicine is by competing the cardiovascular effect that the epinephrine β1-Shou Ti suppresses youngster's naphthol ammonia, and the result descends cardiac contractile force and contraction speed, and slow down conduction and heart rate reduce myocardial oxygen consumption, improve cardiac motion endurance.High selectivity β1-Shou Ti blocker descends peripheral vascular resistance by retardance feritin-a hypertensin system, and cardiac output is reduced, and reaches the effect that brings high blood pressure down.Therefore, such medicine is best suited for the higher high renin hypertension patient of sympathetic tone.Cardiac muscle there is protective effect, is applicable to chronic congestion cardiac insufficiency (CHF).It is called as the neuroendocrine antagonist with ACEI and spiral shell lactone, is particularly useful for the high renin hypertension patient with chronic cardiac insufficiency.Multiselect is used β1-Shou Ti atenolol selectively, clever oversensitive peace bisoprolol clinically at present.The willow phenalgin heart that has α and β1Shou Ti retardation concurrently is fixed, the carvedilol hypotensive effect is stronger, and should with other class compatibility of drugs.
Three) calcium antagonist claims calcium ion antagonist again, and it is more to develop very fast kind, is used for the first-selected dihydropyridine type calcium antagonists of blood pressure lowering.As nifedipine, nitrendipine, nimodipine, nicardipine, western Horizon short of money, felodipine etc., the time of each self-applying is different.Above-mentioned six kinds the longest action time with lacidipine, nitrendipine, felodipine are taken second place, and its excess-three medicine is shorter.Amlodipine action time and lacidipine are close.Such medicine all is to suppress flow of calcium ions to go into cardiac muscle and vascular smooth muscle cell, reduce the cytoplasm calcium ion level, reduce calcium utilization, cause that vascular smooth muscle is loose, reduce vascular resistance and bring high blood pressure down, because pressure decay rate is too fast, action time, the too short sympathetic nerve reflexive tension force that then causes increased, and caused heart rate to be accelerated.This ill effect is the most obvious with fugitive kind such as nifedipine, and the lightest with long-acting kind amlodipine, lacidipine, it is more welcome that long-acting kind is used for blood pressure lowering.But, influence it and apply because of selling at exorbitant prices.
Four) angiotensin converting enzyme inhibitor, energy competitive inhibition Angiotensin-Converting, Angiotensin II generates few, suppress the Kallidin I degraded, peripheral vascular resistance reduces, and makes aldosterone produce minimizing, retention of sodium and water reduces, hypovolemia, comprehensive function make cardiac output and vascular resistance reduce blood pressure drops.Because aldosterone has pool sodium to cause edema, increase the weight of cardiac load, impel between myocardial fibrosis and cardiac muscle illeffectss such as matter change, so such medicine often is used to congested chronic cardiac insufficiency person to protect patient's cardiac muscle.Because the Kallidin I degraded reduces, can produce spastic dry cough by sensitization bronchus inner membrance, about 1-30% hyperpietic is difficult to tolerance to such medicine.Aldosterone generates when reducing, and blood potassium might raise, and when having the drug combination that rises the potassium effect with other, should note monitoring the blood potassium level.Such medicine has captopril, benazepril, enalapril, lisinopril, fosinopril etc.Such medical instrument has the nerve ending of minimizing to discharge epinephrine, reduces Endothelin formation etc., and useful effect is played in the treatment of hypertension.
Five) angiotensin ii receptor antagonist is a class medicine of current research exploitation.Its maximum superior part is the strong point that has kept the angiotensin converting enzyme inhibitor effect, and has overcome its most weakness, and completely without the ill effect that causes paroxysmal spasmodic cough, headache and edema are lacked than calcium ion antagonist, and idol has the effect of rising potassium.Its hypotensive activity certainly to heart failure, protection kidney merit, delays the nephropathy progress, reverses left ventricular hypertrophy, anti-angiogenicly effect such as reinvents, and is similar or stronger with angiotensin converting enzyme inhibitor.At present represent medicine that losartan (losartan trade name losartan) is arranged, Valsartan (Valsartan) reaches (Eprosartan) general Losartan.
Six) alpha-receptor blocker can be treated safely and effectively and changed blood pressure, and its major side effects is a postural hypotension.Blood fat and blood glucose there is positive impact.Therefore, the senile hypertension patient should watch out for the harm of postural hypotension, to having superiority with impaired glucose tolerance or dyslipidemia or hypertension * syndrome patient.Medicine commonly used has furazosin (Terazosin), terazosin, doxazosin (Doxazosin), trimazosin (Trimazosin).The kind that this class medicine has has the effect of alleviating to prostate hyperplasia patient's dysuria, and doxazosin is particularly useful for containing and the patients with hypertension of hyperlipidemia, diabetes, respiratory tract disease and peripheral vascular disease.
In sum, the mechanism of action of six classes treatment hypertension drug has nothing in common with each other, and is final again all by its hypotensive activity is brought into play in angiocardiokinetic useful adjusting.Diuretic, β1-Shou Ti blocker, calcium ion antagonist are selected in this invention, other adds aldosterone antagonists, spiral shell lactone or angiotensin ii receptor antagonist, be combined into a compound medicine according to a certain ratio, can reach the target of the effective blood pressure lowering of multi-faceted coordinated.Diuretic diuresis row sodium reduces blood vessel wall and makes blood vessel loose to the sensitivity of vaso-excitor material, and Peripheral resistance descends, and blood pressure descends thereupon; The β1-Shou Ti blocker makes the cardiac muscle conduction slow, and myocardial contraction descends, and heart rate is slow, and cardiac output reduces, and blood vessel is loose, and external resistance descends, and blood pressure is descended; The calcium ion antagonist reduces flow of calcium ions, and myocardial cell and vascular smooth muscle cell calcium utilization reduce, and a little less than the myocardial contraction, cardiac output reduces, and blood vessel is loose, and peripheral resistance descends, and blood pressure is descended; Angiotensin ii receptor antagonist blocking-up vasotonia reaction makes blood vessel loose, and Peripheral resistance descends, and hypertension is minimized; Spiral shell lactone antagonism pool sodium Zhu Shui, reduction cardiac output, favourable bringing high blood pressure down.All medicine action site differences, the effect that brings high blood pressure down unanimity has realized collaborative on final goal.
The hypertensive pharmaceutical composition of treatment of the present invention, medicine by following weight proportion is formed, calcium ion antagonist 1.5-2.5 part, β1-Shou Ti blocker 1.5-3.5 part, diuretic 2-4 part, aldosterone antagonists 2-4 part, angiotensin ii receptor antagonist 2-5 part, right amount of auxiliary materials.
In hypotensor composition of the present invention, calcium ion antagonist is the mixture of nitrendipine, nifedipine, nimodipine, nicardipine, nisoldipine, Buddhist nun's dagger-axe Horizon, felodipine, lacidipine, amlodipine, one or more medicines of isradipine.
In pharmaceutical composition of the present invention, the β1-Shou Ti blocker is the mixture of atenolol, metoprolol, bisoprolol, labetalol, carvedilol one or more medicines wherein.
In pharmaceutical composition of the present invention, diuretic is the mixture of hydrochlorothiazide, Indapamide one or both medicines wherein.
In pharmaceutical composition of the present invention, aldosterone antagonists is spironolactone.
In pharmaceutical composition of the present invention, angiotensin ii receptor antagonist is the mixture of valsartan, losartan, general Losartan one or more medicines wherein.
In pharmaceutical composition of the present invention, adjuvant is starch and dextrin.
At pharmaceutical composition of the present invention is said tablet or capsule on the pharmaceutics.
Said medicament is a said dosage form on any pharmaceutics, is good with tablet and capsule.
Four, embodiment
Prescription one: it is an amount of that every single agent contains nimodipine, nicardipine mixture 2.5mg, bisoprolol, labetalol mixture 2.2mg, Indapamide 2.7mg, spironolactone 3.3mg, losartan, the mixture 3.8mg of general Losartan, amylodextrin.
Prescription two: the mixture 1.5mg of the mixture 2mg of nitrendipine, nifedipine, atenolol, metoprolol, Indapamide 4mg, spironolactone 2.5mg, valsartan 3.5mg, amylodextrin are an amount of.
Prescription three: mixture 3mg, the hydrochlorothiazide 2mg of the mixture 2.5mg of nisoldipine, Buddhist nun's dagger-axe Horizon, labetalol, carvedilol, spironolactone 3mg, losartan, mixture 4mg part of general Losartan, amylodextrin are an amount of.
Prescription four: the mixture 3mg of the mixture 2.5mg of felodipine, lacidipine, metoprolol, bisoprolol, the mixture 2.6mg of hydrochlorothiazide, spironolactone 2.8mg, general Losartan 5mg, amylodextrin are an amount of.
Prescription five: the mixture 1.5mg of amlodipine, isradipine, bisoprolol 3.5mg, Indapamide 4mg, spironolactone 2mg, valsartan, the mixture 3.2mg of general Losartan, amylodextrin are an amount of.
Prescription six: nitrendipine 2.5mg, hydrochlorothiazide 3.2mg, atenolol 3.3mg, spironolactone 3.5mg, losartan 3.0mg, amylodextrin are an amount of.
Prescription seven: nitrendipine 2.0mg, hydrochlorothiazide 2.5mg, atenolol 3mg, spironolactone 2.5mg, general Losartan 4mg amylodextrin are an amount of.
Prescription eight: Buddhist nun's dagger-axe Horizon 2mg, Indapamide 2mg, atenolol 2.5mg, spironolactone 3mg, losartan 5mg, amylodextrin are an amount of.
Preparation method is: press formula proportion each component drug is mixed, adopt conventional tablet or capsular pharmaceutical technology to be processed into.
In the pharmaceutical composition in the present invention, the decreased heart rate effect of β1-Shou Ti blocker offsets that the calcium ion antagonist reflexive activates sympathetic nerve and the side effect of accelerating heart rate.The rising serum potassium of spiral shell lactone or angiotensin ii receptor antagonist is used for offsetting diuretic row potassium and reduces the serum potassium side effect.The spiral shell lactone to resisting myocardial fibrillation, matter changes and the formation of Endothelin in the heart, and cardiac muscle is had more sure protective effect.Moreover the content of each composition is less, and side effect is cancelled out each other, and can guarantee that the dosage related side effects significantly reduces, even can reach and do not have institute and perceive the degree that is difficult to cause harm.
We observe half a year with this medicine treatment continuously to 65 routine patients with hypertension, and all systolic pressures of generally taking medicine are on average reduced to 128.85 ± 19.20mmHg by 179.6 ± 30.45mmHg, descend 29.29%, maximum reducing amplitude 48mmHg; Diastolic pressure is reduced to 79.4 ± 10.90mmHg by 106.2 ± 12.08MMHG after one week, descends 25.25%, and the maximum reducing amplitude is 52mmHg; One all arteries flatten reduces to 95.98 ± 12.01mmHg by 131.2 ± 16.15mmHg, descends 26.87%.Systolic pressure diastolic pressure and the mean arterial pressure maintenance that continues to take medicine is stable, (the systolic pressure value accounts for 84.62% less than 135mmHg, diastolic blood pressure values less than 85mmHg person to this group patient controlling of blood pressure to desirable level, the nonresponder only accounts for 4.61%, total effective rate reaches 95.38%, the heart rate average out to is 84.9 times/minute before the medication, after the medication average 77.0 ± 5.21 times/minute, front and back contrast difference's highly significant, the serum levels of BS, CH, TG, Cr, BUN, K+, Na+, CL-does not have significant change before and after the treatment, and the rhythm of the heart, electrocardiogram do not have significant change.Mostly behind the symptom treatments such as health is weak, dizzy, headache, cardiopalmus, tachypnea disappear or alleviate the asymptomatic case that increases the weight of.
The characteristics of pharmaceutical composition of the present invention are: do not contain Angiotensin-Converting in the composition composition and suppress Agent, thereby guarantee can not occur the ill-effects such as paroxysmal spasmodic cough, be applicable to be expected to most hyperpietics into Pharmaceutical preparation for a kind of compound control blood pressure.
Claims (10)
1, the hypertensive pharmaceutical composition of a kind of treatment, it is characterized in that forming calcium ion antagonist 1.5-2.5 part, β1-Shou Ti blocker 1.5-3.5 part, diuretic 2-4 part, aldosterone antagonists 2-4 part, angiotensin ii receptor antagonist 2-5 part, right amount of auxiliary materials by the medicine of following weight proportion.
2, pharmaceutical composition according to claim 1, the medicine that it is characterized in that weight proportion is formed calcium ion antagonist 1.8-2.3 part, β1-Shou Ti blocker 2-3 part, diuretic 2.5-3.5 part, aldosterone antagonists 2.5-3 part, angiotensin ii receptor antagonist 3-4 part, right amount of auxiliary materials.
3, according to the described pharmaceutical composition of claim 1-2, the medicine that it is characterized in that weight proportion is formed 2 parts of calcium ion antagonists, 2.5 parts of β1-Shou Ti blocker, 3 parts of diuretic, 2.8 parts of aldosterone antagonistses, 3.5 parts of angiotensin ii receptor antagonist, right amount of auxiliary materials.
4,, it is characterized in that calcium ion antagonist is the mixture of nitrendipine, nifedipine, nimodipine, nicardipine, nisoldipine, Buddhist nun's dagger-axe Horizon, felodipine, lacidipine, amlodipine, one or more medicines of isradipine according to the described pharmaceutical composition of claim 1-3.
5,, it is characterized in that raw material β1-Shou Ti blocker is the mixture of atenolol, metoprolol, bisoprolol, labetalol, carvedilol one or more medicines wherein according to the described pharmaceutical composition of claim 1-3.
6,, it is characterized in that diuretic is the mixture of hydrochlorothiazide, Indapamide one or both medicines wherein according to the described pharmaceutical composition of claim 1-3.
7. according to the described pharmaceutical composition of claim 1-3, it is characterized in that aldosterone antagonists is spironolactone.
8,, it is characterized in that angiotensin ii receptor antagonist is the mixture of valsartan, losartan, general Losartan one or more medicines wherein according to the described pharmaceutical composition of claim 1-3.
9,, it is characterized in that adjuvant is starch and dextrin according to the described pharmaceutical composition of claim 1-3.
10,, it is characterized in that this medicament is said tablet or a capsule on the pharmaceutics according to the described pharmaceutical composition of claim 1-3.
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| CN 200410023771 CN1562369A (en) | 2004-03-29 | 2004-03-29 | Combination of medication for curing high blood pressure |
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| CN 200410023771 CN1562369A (en) | 2004-03-29 | 2004-03-29 | Combination of medication for curing high blood pressure |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006119692A1 (en) * | 2005-05-08 | 2006-11-16 | Cp Drug Development Co., Ltd. | A medicament for the treatment of hypertension |
| CN101040860B (en) * | 2006-03-22 | 2010-05-26 | 北京华安佛医药研究中心有限公司 | Pharmaceutical composition for treatment of lower urinary tract diseases |
| CN101869562A (en) * | 2010-05-06 | 2010-10-27 | 施慧达药业集团(吉林)有限公司 | Levamlodipine compound medicinal preparation |
| CN101890011B (en) * | 2009-05-22 | 2013-05-01 | 北京奥萨医药研究中心有限公司 | Pharmaceutical composition containing amlodipine and stilbestrol |
-
2004
- 2004-03-29 CN CN 200410023771 patent/CN1562369A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006119692A1 (en) * | 2005-05-08 | 2006-11-16 | Cp Drug Development Co., Ltd. | A medicament for the treatment of hypertension |
| CN100389830C (en) * | 2005-05-08 | 2008-05-28 | 广州市施柏医药科技有限公司 | Medicinal composition for treating high blood pressure |
| CN101040860B (en) * | 2006-03-22 | 2010-05-26 | 北京华安佛医药研究中心有限公司 | Pharmaceutical composition for treatment of lower urinary tract diseases |
| CN101890011B (en) * | 2009-05-22 | 2013-05-01 | 北京奥萨医药研究中心有限公司 | Pharmaceutical composition containing amlodipine and stilbestrol |
| CN101869562A (en) * | 2010-05-06 | 2010-10-27 | 施慧达药业集团(吉林)有限公司 | Levamlodipine compound medicinal preparation |
| WO2011137601A1 (en) * | 2010-05-06 | 2011-11-10 | 施慧达药业集团(吉林)有限公司 | Compound pharmaceutical formulation of levoamlodipine |
| CN101869562B (en) * | 2010-05-06 | 2011-12-07 | 施慧达药业集团(吉林)有限公司 | Levamlodipine compound medicinal preparation |
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Effective date of registration: 20070824 Address after: 253200 Xiajin County People's Hospital of Shandong Province Applicant after: Yuan Changli Co-applicant after: He Tingbang Address before: Xiajin County People's Hospital of Shandong Province Applicant before: Wang Deshan Co-applicant before: Wang Xiaoying |
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