CN106310274A - Pharmaceutical composition for preventing cardiovascular diseases - Google Patents

Pharmaceutical composition for preventing cardiovascular diseases Download PDF

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Publication number
CN106310274A
CN106310274A CN201610345869.9A CN201610345869A CN106310274A CN 106310274 A CN106310274 A CN 106310274A CN 201610345869 A CN201610345869 A CN 201610345869A CN 106310274 A CN106310274 A CN 106310274A
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content
pharmaceutical composition
aspirin
group
folic acid
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王念
徐希平
于多
张磊
白洁
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BEIJING AOSA MEDICINE RESEARCH CENTRE Co Ltd
SHENZHEN AOSA PHARMACEUTICAL CO Ltd
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BEIJING AOSA MEDICINE RESEARCH CENTRE Co Ltd
SHENZHEN AOSA PHARMACEUTICAL CO Ltd
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Publication of CN106310274A publication Critical patent/CN106310274A/en
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    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • 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
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • 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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
    • A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention relates to a synergistic antihypertensive lipid-lowering pharmaceutical composition and the use of the pharmaceutical composition. The pharmaceutical composition comprises a pharmaceutical dosage of one of HMG-CoA reductase inhibitors, a pharmaceutical dosage of one of antihypertensive drugs, aspirin, folic acid and 5-methylaretetrahydrofolate, and a pharmaceutically acceptable carrier. The indication is hypertension accompanied with hyperlipidemia. The pharmaceutical composition can also be used as a primary drug for prevention of cardiovascular diseases. By the implementation of the invention, the pharmaceutical composition for the specific use for patients can improve the compliance of the patients, facilitate administration of the patients and reduce medical expenses, so that the pharmaceutical composition has relatively good market prospects.

Description

A kind of pharmaceutical composition preventing cardiovascular disease
Technical field
The present invention relates to a kind of containing depressor, hydroxyl first glutaryl coenzyme A (HMG-CoA) reductase inhibitor, Ah Si Woods and the medical composition and its use of folic acid.The invention belongs to pharmaceutical field.
Background technology
Cardiovascular disease is the one of the main reasons of human death, including coronary heart disease (myocardial infarction) and apoplexy (being commonly called as apoplexy).The sickness rate of China's cardiovascular disease and nearly 20 years of case fatality rate are in being gradually increasing trend, and its major reason is to send out Sick risk factor is being on the increase.These risk factors include hypertension, dyslipidemia, atherosclerosis, smoking, drink Deng.Therefore, take effective prevention measure, to reduce the harm of various controllable risk factors be the prevention painstaking effort such as coronary heart disease, apoplexy The key that pipe illness events occurs.
In the risk factor causing apoplexy, hypertension is most important and modal reason.Shrink pressure often decline 5～ 10mmHg or diastolic pressure often decline 2～5mmHg, and Stroke risk reduces by 30%～40%.In addition to hypertension, dyslipidemia, height Plasma homocysteine is also the cardiovascular disease risk factor that coexists more typically, has data to show, the high blood more than 50% Pressure patient is attended by dyslipidemia, baseline blood pressure and serum cholesterol and raises the incidence rate that can sharply increase cardiovascular disease. A large amount of clinical researches show, the use in conjunction of depressor and lipid lowerers can reduce morbidity and the death of cardiovascular disease.The U.S. Pfizer releases compound drug " Caduet " in 2004, and it is i.e. to be cut down with hypolipidemic atropic by antihypertensive amlodipine Statin combines, and clinical research proves that Caduet can substantially reduce blood pressure and blood cholesterol levels, makes more than 80% patient Reach target blood pressure and target cholesterol levels, coronary heart disease risk can be significantly reduced.
The coronary heart disease of 85% causes due to coronary atherosclerosis, and atherosclerosis and dyslipidemia (lipidosis) is directly related, even the most effectively reduce blood fat can delay reversal of atherosclerosis.Dyslipidemia table It is now one or more water in triglyceride (TG) in blood, T-CHOL (TC), low-density lipoprotein cholesterol (LDL-C) Flat raise or HDL-C (HDL-C) level reduce (HDL-C reduce be coronary heart disease independent hazard factor it One).Clinical research shows, reduces serum TC and LDL-C level with simvastatin or pravastatin, not only can reduce coronary heart disease thing Part incidence rate reaches 30%～40%, and reduces total case fatality rate and reach 22%～30%, and minimizing is done coronary artery intracavity and formed art And the incidence rate of apoplexy.
Long-term hyperlipidemia state also can produce induration to cells of vascular wall film and hemocyte film, makes erythrocyte membrane Mobility reduces, and erythrocyte deformability declines, thus microcirculation blood stasis, blood flow are slack-off, blood viscosity increases (hemorheology Learn abnormal), it is easy to form thrombosis, make the dangerous increase that embolic cardiocerebrovasculaevents events occurs.Additionally, lipid in atheromatous plaque Composition and content also affect the stability of speckle, and lipid has an effect on thrombin and fibrinolytic system.Therefore, application presses down Platelet aggregation processed or other hemorheological measure of improvement are conducive to the most effectively preventing the bolt such as myocardial infarction, apoplexy The generation of plug sexually transmitted disease (STD) disease.
The statins antilipemic drugs such as atorvastatin, pravastatin, simvastatin belong to HMG-CoA reductase suppression Agent, the hydrolyzate after oral absorption suppresses the rate-limiting enzyme hydroxyl first glutaryl during cholesterol biosynthesis auxiliary the most competitively Enzyme A reductase, makes the synthesis of cholesterol reduce, also make low density lipoprotein receptor synthesis increase, Main Function position at liver, Result makes blood TC and LDL-C level reduce, and moderate reduces blood TG level and increases HDL-C level, is used for clinically treating high gallbladder Sterin mass formed by blood stasis and combined hyperlipidemia familial, be also used for the prevention of coronary heart disease.HMG-CoA reductase inhibitor class medicine can also subtract LDL-C in few speckle, recovers inner skin cell function, promotes the stability of atheromatous plaque, therefore the benefit of its treatment is not detected in Cholesterol raises patient, also sees the normal patients with coronary heart disease of cholesterol.
Aspirin has suppression platelet aggregation thus the pharmacological action of inhibition thrombosis.It is by irreversibly Suppress hematoblastic epoxidase, reduce the generation of prostaglandin and play this effect.But aspirin is to vascular endothelial cell Cycloxygenase effect weak, to prostacyclin I2(PGI2) generation have little to no effect.This is owing to platelet itself can not be closed Become epoxidase, when cyclooxigenase activity is suppressed, it is necessary to treat the platelet of new life to enter in blood circulation and could continue synthesis Thromboxane A2, and vascular endothelial cell has the ability of synthesizing epoxy enzyme, so the aspirin of application low dosage only suppresses The oxidasic activity of platelet internal ring, can be clinically used for the prevention and treatment of diseases such as angina pectoris, myocardial infarction.Aspirin When the secondary prevention of coronary heart disease, it is recommended that dosage is in the range of 50mg～325mg, the most conventional with 50～150mg the most again. The result that one data to disclosed issue carry out meta analysis shows, aspirin and pravastatin are in cardiovascular disease Secondary prevention has complementary enlarge-effect.Research worker find above two medicine use in conjunction be used alone Ah Si Woods is compared with being used alone pravastatin, and the danger of myocardial infarction reduces by 31% and 26% respectively, the danger of Ischemic Stroke Property the most respectively reduce by 29% and 31%.
Folic acid belongs to vitamin B group, be nucleic acid, cell growth and tissue repair necessary to element.Grinding in recent years Studying carefully discovery, it reduces cardiovascular event generation wind by reducing homocysteine (homocysteine, Hcy) in blood Danger.This R&D team has delivered meta-analysis (Wang X, an et in 2007 at " The Lancet (lancet) " magazine al.Efficacy of folic acid supplementation in stroke prevention:a meta- analysis.Lancet,2007,369:1876).Result shows, Supplement of folic acid can reduce risk of stroke 18% (p < 0.05).When for primary prevention, folic acid reduces risk of stroke 25%；When being applied to not accept food adds folic acid During crowd, Supplement of folic acid reduces risk of stroke 25%；When Plasma Hcy can be reduced by more than 20% by Supplement of folic acid, its fall Low risk of stroke reaches 23%；And when Supplement of folic acid curative effect was more than 3 years, it reduces risk of stroke and reaches 29%.
At present in the compound medicine developmental research of multiple cardiovascular risk factors, it is that blood pressure lowering, blood fat reducing etc. are normal mostly The treatment seen, intervene drug regimen, and have ignored the process to some other risk factor, and these rare risk factors Important pathological effect may be played in induction vascular incident.For overcoming the defect of this quasi-tradition compositions, the present invention adds Entering and process hematoblastic suppression and the intervention to high Hcy this Novel Risk Factors of mass formed by blood stasis, experiment displays that this compositions There is beyond thought cardiovascular prevention effect.
Summary of the invention
It is an object of the invention to overcome the deficiency existed for clinical application during the situations such as hypertension companion's dyslipidemia, it is provided that A kind of more preferable pharmaceutical composition of preventing cardiovascular events effect, this effect be embodied in prevention or delay atherosclerosis, Reduce the vascular events risk aspects such as apoplexy.For achieving the above object, the present invention is by the following technical solutions:
A kind of pharmaceutical composition, including:
(1) one of the depressor of medicinal content, depressor is selected from angiotensin converting enzyme inhibitor (ACEI), blood vessel (beta receptor blocks for angiotensin receptor blocker (ARB), calcium channel blocker (CCB), diuretic, receptor,β blocker Agent)；
(2) one in the HMG-CoA reductase inhibitor of medicinal content；
(3) aspirin of medicinal content；
(4) folic acid of medicinal content or 5-methyltetrahydrofolate；With
(5) acceptable carrier on pharmaceutics.
Wherein " medicinal content " refers to have the amount of pharmacological action collaborative, that prevent or treat.
Further, preferably
(1) one of the depressor of 1.25mg～300mg, depressor is selected from ACEI, ARB, CCB, profit
Urine agent or beta-blocker；
(2) one in the HMG-CoA reductase inhibitor of 0.1mg～100mg；
(3) aspirin of 50mg～325mg；
(4) folic acid of 0.1mg～2.0mg or 5-methyltetrahydrofolate；With
(5) acceptable carrier on pharmaceutics.
More preferably
(1) one of the depressor of 2.5mg～100mg, depressor is selected from ACEI, ARB, CCB, diuretic or beta receptor resistance Stagnant dose；
(2) one in the HMG-CoA reductase inhibitor of 1mg～80mg；
(3) aspirin of 50mg～150mg；
(4) folic acid of 0.2mg～2.0mg or 5-methyltetrahydrofolate；With
(5) acceptable carrier on pharmaceutics.
In invention, HMG-CoA reductase inhibitor medicine refers to (but not limited to) atorvastatin (atorvastatin), simvastatin (simvastatin), Pitavastatin (pitavastatin), pravastatin (pravastatin), lovastatin (lovastatin), fluvastatin (fluvastatin), cerivastatin (cerivastatin), Rosuvastatin (rosuvastatin), itavastatin (itavastatin), itavastatin (nisvastatin), the one in bervastatin (bervastatin), mevastatin (mevastatin).
In the present invention, atorvastatin content be 5mg～80mg, simvastatin content be 5mg～80mg, Pitavastatin Content is 1mg～4mg, lovastatin content is 5mg～80mg, fluvastatin content is 5mg～80mg, pravastatin content is 5mg～80mg, Rosuvastatin content are 5mg～80mg, and the active metabolite of above-mentioned substance or salt content are with corresponding Above-mentioned substance content is equal to.
In the present invention, depressor selected from ARB, ACEI, CCB, beta-receptor antagonist and diuretic, wherein ARB include but It is not limited to: losartan (losartan), valsartan (valsartan), Irb (irbesartan), telmisartan (telmisartan), Candesartan (candesartan)；ACEI includes but not limited to: captopril (captopril), according to that Puli (enalapril), benazepril (benazepril), lisinopril (lisinopril), ramipril (ramipril), Fosinopril (fosinopril), cilazapril (cilazapril), perindopril (perindopril)；Beta-receptor antagonist Include but not limited to: Propranolol (propranolol), metoprolol (metoprolol), atenolol (atenolol), times Ta Luoer (betaxolol), bisoprolol (bisoprolol), Carvedilol (carvedilol), labetalol (labetalol)；Diuretic includes but not limited to: hydrochlorothiazide (hydrochlorothiazide), chlorothiazide (chlorothiazide), spironolactone (spirolactone), triamterene (triamterene), amiloride (amiloride), furosemide (furosemide), indapamide (indapamide)；CCB includes but not limited to: nifedipine (nifedipine), nicardipine (nicardipine), nitrendipine (nitrendipine), felodipine (felodipine), amlodipine (amlodipine), lacidipine (lacidipine), lercanidipine (lercanidipine), verapamil (verapamil), diltiazem (diltiazem).
In the present invention, losartan content be 50～100mg, valsartan content be 80～160mg, Irb content be 150～300mg, Captopril Content be 12.5～50mg, enalapril content be 10～20mg, benazepril content be 10～ 20mg, lisinopril content are 10～20mg, Propranolol content is 10～20mg, metoprolol content is 25～50mg, Ah For Luo Er content be 50～100mg, betaxolol content be 10～20mg, hydrochlorothiazide content be 12.5mg, chlorothiazide content Be 25～50mg, spironolactone content be 25～40mg, amiloride content be 5～10mg, nifedipine content be 5～10mg, Nicardipine content is 40mg, nitrendipine content is 10mg, amlodipine content is 5～10mg, lacidipine content be 4～ 6mg, lercanidipine content are 10～20mg, and active metabolite or the salt content of above-mentioned substance contain with corresponding above-mentioned substance Amount equivalent.
In the present invention, the content of folic acid or 5-methyltetrahydrofolate is preferably: folic acid 0.4mg～1.6mg, or 5-methyl Tetrahydrofolic acid 0.4mg～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is atorvastatin, and content is 5mg～80mg；Depressor is losartan, and content is 50～100mg；Aspirin content is 50mg～325mg；Folate content is 0.1mg～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is atorvastatin, and content is 5mg～80mg；Depressor is valsartan, and content is 80～160mg；Aspirin content is 50mg～325mg；Folate content is 0.1mg～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is atorvastatin, and content is 5mg～80mg；Depressor is captopril, and content is 12.5～50mg；Aspirin content is 50mg～325mg；Folic acid contains Amount is 0.1mg～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is atorvastatin, and content is 5mg～80mg；Depressor is enalapril, and content is 10～20mg；Aspirin content is 50mg～325mg；Folate content For 0.1mg～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is Pitavastatin, and content is 1mg ～4mg；Depressor is Propranolol, and content is 10～20mg；Aspirin content is 50mg～325mg；Folate content is 0.1mg～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is Pitavastatin, and content is 1mg ～4mg；Depressor is metoprolol, and content is 25～50mg；Aspirin content is 50mg～325mg；Folate content is 0.1mg～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is Pitavastatin, and content is 1mg ～4mg；Depressor is hydrochlorothiazide, and content is 12.5mg；Aspirin content is 50mg～325mg；Folate content is 0.1mg ～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is Pitavastatin, and content is 1mg ～4mg；Depressor is chlorothiazide, and content is 25～50mg；Aspirin content is 50mg～325mg；Folate content is 0.1mg ～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is simvastatin, and content is 5mg ～80mg；Depressor is nifedipine, and content is 5～10mg；Aspirin content is 50mg～325mg；Folate content is 0.1mg～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is simvastatin, and content is 5mg ～80mg；Depressor is amlodipine, and content is 5～10mg；Aspirin content is 50mg～325mg；Folate content is 0.1mg～2.0mg.
In the pharmaceutical composition that the present invention provides, described HMG-CoA reductase inhibitor is simvastatin, and content is 5mg ～80mg；Depressor is lacidipine, and content is 4～6mg；Aspirin content is 50mg～325mg；Folate content is 0.1mg～2.0mg.
The pharmaceutical composition that the present invention provides has lowering blood pressure and blood fat, suppression platelet aggregation and fall Hcy effect.
The pharmaceutical composition that the present invention provides has the atherosclerotic effect of preventing and treating, and this atherosclerosis can be drawn Harbor, the secondary lesion of the organ such as brain, kidney, eye, including coronary heart diseases and angina pectoris, myocardial infarction, acute coronary syndromes Levy, apoplexy, arteriolar nephrosclerosis, peripheral arterial disease, retinal arteriosclerosis etc..
The present invention also provides for aforementioned pharmaceutical compositions in preparation for preventing, treat or delay hypertension companion's dyslipidemia to draw Purposes in the medicine of the target organ damage risen.The target organ damage that hypertension companion's dyslipidemia causes, refers to due to hypertension And/or dyslipidemia cause the heart, brain, kidney, the secondary lesion of the organ such as eye, including apoplexy, atherosclerosis, coronary disease Disease, left ventricular hypertrophy, angina pectoris, myocardial infarction, acute coronary syndrome, Heart function fails, benign arteriolar nephrosclerosis Disease, heart failure, arrhythmia, primary cardiac all standing, renal hypofunction, pernicious arteriolar nephrosclerosis, peripheral arterial Disease, retinal arteriosclerosis or Hypertensive Fundus pathological changes.
The pharmaceutical composition that the present invention provides also has the effect reducing cardiocerebrovasculaevents events risk, wherein reduces heart and brain blood Pipe event risk refers to reduce the diseases such as acute coronary syndrome, angina pectoris, myocardial infarction, apoplexy or coronary heart disease is high-risk Incidence rate.
The dosage form of this pharmaceutical composition includes but not limited to conventional tablet, bilayer tablet, multilayer tablet, slow releasing tablet, list Room controlled release tablet, dual chamber controlled release tablet, pore type controlled release tablet, sublingual lozenge, oral cavity quick disintegrating slice, dispersible tablet, enteric coatel tablets, granule Agent, pill, enteric coated capsule, delayed-release tablet, regularly/position releasing piece, conventional capsule, slow releasing capsule, controlled release capsule, containing micropill Or the dosage form such as the capsule of small pieces, pH dependent form capsule, granule, oral liquid, membrane or patch containing micropill or small pieces.
Possibly together with pharmaceutics acceptable carrier in this pharmaceutical composition, can be made into common oral preparation, including ordinary tablet Agent, conventional capsule, granule etc., when making tablet, described pharmaceutically acceptable carrier includes contributing to joining reactive compound Make excipient and the accessory drugs of pharmaceutical formulation, such as starch, microcrystalline Cellulose, inorganic salts, sucrose, dextrin, lactose, Icing Sugar, Portugal The compositions of one or more materials of grape sugar, sodium chloride, cysteine, citric acid and sodium sulfite etc., belongs to this area normal Know.
The invention has the beneficial effects as follows:
HMG-CoA reductase inhibitor/antihypertensive drugs/aspirin/folic acid tetrad pharmaceutical composition that the present invention provides There is the synergism lowering blood pressure and blood fat on obvious pharmacology, pharmacodynamics, prevent and treat atherosclerosis, reduction heart and brain The danger that vascular events occurs.Above-mentioned pharmacological experiment study shows, HMG-CoA reductase inhibitor/antihypertensive drugs/Ah Si During woods/folic acid drug combination, its lowering blood pressure and blood fat, suppress platelet aggregation and improve hemorheology effect and be better than alone HMG-CoA reductase inhibitor medicine；HMG-CoA reductase inhibitor/antihypertensive drugs/aspirin/folic acid tetrad medicine group Compound is in terms of atherosclerosis, protection blood vessel endothelium, reduction incidence of stroke, and its action effect is notable.Therefore, originally Invention is significantly improved meaning for existing drug therapy techniques.
The present invention also provides for aforementioned pharmaceutical compositions in preparation for preventing, treat or delay hypertension companion's dyslipidemia to draw Purposes in the medicine of the target organ damage risen.The target organ damage that hypertension companion's dyslipidemia causes, refers to due to hypertension And/or dyslipidemia cause the heart, brain, kidney, the secondary lesion of the organ such as eye, including apoplexy, atherosclerosis, coronary disease Disease, left ventricular hypertrophy, angina pectoris, myocardial infarction, acute coronary syndrome, Heart function fails, benign arteriolar nephrosclerosis Disease, heart failure, arrhythmia, primary cardiac all standing, renal hypofunction, pernicious arteriolar nephrosclerosis, peripheral arterial Disease, retinal arteriosclerosis or Hypertensive Fundus pathological changes.
Cardiocerebrovasculaevents events danger refers to the individual patients generation cardiovascular and cerebrovascular disease relative to whole crowd Risk.Nearly more than ten years, in cardiovascular and cerebrovascular disease research field, " reducing cardiocerebrovasculaevents events dangerous " more and more becomes measurement medicine Thing curative effect or the leading indicator of therapeutic scheme, some large-scale clinical trials are all to select this kind of index as clinical endpoint in the world 's.The stanin fat-reducing medicament of pharmaceutical dosage, pharmaceutical dosage antihypertensive drugs, pharmaceutical dosage aspirin and the medicine that the present invention provides The pharmaceutical composition formed with the folacin compound of dosage has obvious synergism in terms of reducing incidence of stroke, and Its effect is significantly stronger than the effect that these medicines are used alone.
In view of above-mentioned cooperative effect beneficial effect in clinic, present invention also offers the HMG-of above-mentioned pharmaceutical dosage The pharmaceutical composition of CoA reductase inhibitor, antihypertensive drugs, aspirin and folic acid is used for blood pressure lowering, preventing and treating tremulous pulse in preparation The atherosis application in medicine；The present invention also provides for aforementioned pharmaceutical compositions in preparation for reducing cardiocerebrovasculaevents events wind Application in the medicine of danger.It addition, by the enforcement of the present invention, it is provided that to the pharmaceutical composition of this special-purpose of patient, can To improve patient compliance, make patient take medicine conveniently, reduce medical expense, therefore there is preferable market prospect.
Detailed description below is to further illustrate the present invention.
Detailed description of the invention
Embodiment 1: prepared by compound recipe atorvastatin/Propranolol/aspirin/folic acid tablet
Prescription is following (1000):
Atorvastatin 10g
Propranolol 10g
Aspirin 75g
Folic acid 0.4g
Carboxymethyl starch sodium 20g
Calcium hydrogen phosphate 170g
10% polyvidone aqueous solution is appropriate
Magnesium stearate 1%
Preparation method: supplementary material was pulverized 80 mesh sieves, drying for standby.Take atorvastatin 10g, Propranolol 10g, Ah A department woods 75g and folic acid 0.4g, according to equal increments method mix homogeneously, adds carboxymethyl starch sodium 20g, calcium hydrogen phosphate 170g, presses Uniformly mix according to equal increments method, folic acid is dissolved in binding agent 10% polyvidone aqueous solution, add binding agent and make soft in right amount Material, 30 mesh granulations, 40～45 DEG C of dry 3h；30 mesh granulate, add the mixing of appropriate magnesium stearate, with No. 8 drifts after assay, Tabletting, to obtain final product.Preparation process notes lucifuge, after product inspection is qualified, aluminium-plastic bubble plate packing, keeps in Dark Place.The compound recipe made In tablet, every contains atorvastatin 10mg, Propranolol 10mg, aspirin 75mg, folic acid 0.4mg.
Embodiment 2: prepare compound tablet
Preparation method: with embodiment 1.
Constituent and the content of 14 kinds of compound recipes are shown in Table 11.
1 15 kinds of compound active pharmaceutical formulation compositions of table
Embodiment 3: prepared by compound recipe atorvastatin/enalapril/aspirin/folic acid capsule
Prescription is following (1000):
Preparation method: supplementary material was pulverized 80 mesh sieves, drying for standby.Take atorvastatin 10g, enalapril 20g, Ah A department woods 75g and folic acid 0.4g, according to equal increments method mix homogeneously, adds 100～200g lactose, 15～25g carboxymethyl starch Sodium (the definite consumption of adjuvant adjusts according to active medicine consumption), uniformly mixes according to equal increments method, with 10% polyvidone ethanol Solution makes soft material, and 20 mesh sieves are pelletized, and 60 DEG C are dried about 2h, 20 mesh sieve granulate, and the water content controlling granule is 2-3%, will be dry Granule after dry is mixed homogeneously with recipe quantity magnesium stearate, and semi-finished product detect, and measures content, loads Capsules, to obtain final product 1000 seed lac capsules.Preparation process notes lucifuge.The qualified rear aluminium-plastic bubble plate packing of product inspection, keeps in Dark Place.The compound recipe made In capsule, every contains atorvastatin 10mg, enalapril 20mg, aspirin 75mg, folic acid 0.4mg.
Embodiment 4: prepare compound capsule
Preparation method: with embodiment 3.Constituent and the content of 14 kinds of compound recipes are shown in Table 1.
Embodiment 5: prepared by compound recipe Rosuvastatin/valsartan/aspirin/folic acid granule
Prescription is following (1000 bags):
Preparation method: supplementary material was pulverized 80 mesh sieves, drying for standby.Take Rosuvastatin 10g, valsartan 80g, A Si Woods 100g and folic acid 0.8g, according to equal increments method mix homogeneously, adds 750～850g lactose, 10～20g carboxymethyl starch Sodium (the definite consumption of adjuvant adjusts according to active medicine consumption), uniformly mixes according to equal increments method, with 10% polyvidone ethanol Solution makes soft material, and 18 mesh sieves are pelletized, and 60 DEG C are dried about 2h, 16 mesh sieve granulate, and the water content controlling granule is less than 2%, will Dried granule is mixed homogeneously with recipe quantity orange flavor, aspartame, magnesium stearate, and semi-finished product detect, and mensuration contains Amount, loads aluminum bag and i.e. obtains 1000 bags.Preparation process notes lucifuge.In the compound granule made, every bag contains Rosuvastatin 10mg, valsartan 80mg, aspirin 100mg and folic acid 0.8mg
Embodiment 6: preparation compound granule
Preparation method: with embodiment 5.Constituent and the content of 14 kinds of compound recipes are shown in Table 1.
Embodiment 7；Atorvastatin+valsartan+blood fat reducing of aspirin+folic acid on rats, blood pressure lowering, antiplatelet Aggregation
1, modeling: SHR rat 70, WKY rat 10,5-6 week old, male and female half and half, body weight 130～160g, 10 WKY Rat makees normal group, feeds normal diet, and remaining rat feeds high fat homomethionin feedstuff (formula: cholesterol 1.25%, propyl group every day Thiouracil 0.2%, sodium cholate 0.5%, Adeps Sus domestica 12.0%, methionine 3%, normal diet 83.05%).After 4 weeks, to all Rat carries out blood pressure detecting, and take a blood sample survey blood fat and HCY, to confirm hypertension, hyperlipemia height HCY model modeling success.
2, it is grouped and is administered: taking above-mentioned modeling success rat 60, being randomly divided into 6 groups (often groups 10), by being administered difference It is divided into model group, atorvastatin+valsartan+aspirin+folic acid (0.5+4+3.75+0.04) mg/kg group, atorvastatin + valsartan+aspirin+folic acid (1+8+7.5+0.08) mg/kg group, atorvastatin+valsartan+aspirin+folic acid (2+ 16+15+0.16) mg/kg group, atorvastatin+aspirin+folic acid (1+7.5+0.08) mg/kg group, aspirin+folic acid (7.5+0.08) mg/kg group, separately has a normal group, totally 7 groups.When other group gastric infusion, normal group and model group rats give Respective volume solvent gavage.In experimentation, in addition to normal rats feeds normal diet, remaining is respectively organized rat and continues to feed high fat height Methionine feed.Weigh weekly once for each group, adjust dosage, successive administration 12 weeks according to body weight.
3, Testing index: (1) lipid determination took blood after 12 weeks, measures according to test kit description and surveys serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C)；(2) rat serum is detected after blood pressure determination is administered 12 weeks Pressure；(3) platelet aggregation rate, (ratio is turbid with ADP as platelet aggregation for Determination of Blood Rheology platelet aggregation instrument Method) measure maximum platelet aggregation rate (PARmax), measure the ginseng such as whole blood viscosity, Plasma Viscosity with fully automatic blood rheology instrument Number；
4, statistical method: measurement data is usedRepresenting, data statistics processes and uses SPSS13.0 statistical package, and two Mean compares employing t inspection, compares employing variance analysis between many groups.
5, result:
(1) atorvastatin+valsartan+aspirin+folic acid on rats blood fat affected for the 12nd weekend, big with normal group Mus is compared, and model group rats TC, TG, LDL-C significantly raise；Compare with model group, atorvastatin+valsartan+aspirin+ Folic acid variant dosage ratio group, atorvastatin+aspirin+folic acid group rat TC, TG, LDL-C all significantly reduces, especially Reduce as atorvastatin high dose (2mg/kg) more notable, and between senior middle school's low dose group, have pronounced amount effect relationship, and effect It is superior to atorvastatin+aspirin+folic acid group；And aspirin+folic acid group rat TC, TG, LDL-C level is the most notable Change.It is shown in Table 2.
Table 2 atorvastatins+valsartan+aspirin+folic acid on hypertension companion hyperlipemia rat blood fat impact ( N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。
(2) atorvastatin+valsartan+aspirin+folic acid on rats blood pressure affected for the 12nd weekend, with model group ratio Relatively, atorvastatin+valsartan+aspirin+folic acid variant dosage ratio group rat blood pressure all significantly reduces, when with atropic Cut down statin and aspirin reduces more notable when share；And atorvastatin+aspirin+folic acid group, aspirin+folic acid group Rat blood pressure level does not has significant change.It is shown in Table 3.
Table 3 atorvastatins+valsartan+aspirin+folic acid on hypertension companion hyperlipemia rat blood pressure impact ( N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。
(3) atorvastatin+valsartan+aspirin+folic acid on rats platelet aggregation, hemorheological impact with Normal rats compares, and model group rats whole blood viscosity, plasma viscosity significantly raise, and show: hyperlipemia rat presents blood The change that rheological characteristic reduces.Compare with model group, atorvastatin+valsartan+variant dosage ratio of aspirin+folic acid Group, atorvastatin+aspirin+folic acid group, aspirin+folic acid group, rat whole blood and plasma viscosity all have in various degree Reduce (being shown in Table 3), point out atorvastatin, valsartan and aspirin all to have and improve hemorheology effect, when three share Effect strengthens.On the other hand, comparing with normal rats, model group rats platelet aggregation rate increases；Compare with model group, Ah Atorvastatin+aspirin+folic acid variant dosage ratio group, atorvastatin+aspirin+folic acid group, aspirin+leaf Acid group rat platelet aggregation rate reduces the most in various degree, and especially as aspirin high dose (15mg/kg), this anti-blood is little Plate aggregation is more notable, is shown in Table 4.
Table 4 atorvastatins+valsartan+aspirin+folic acid is little to hypertension companion's hyperlipemia rat hemorheology, blood The impact of plate aggregation rate (N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。
Embodiment 8: the protective effect of Rosuvastatin+amlodipine+aspirin+folic acid on rats target organ
1, modeling: SD rat 100,5-6 week old, all-male, body weight 140～160g, select 10 rats to make sham-operation Group, feeds normal diet, and remaining rat carries out 2K1C operation one week after, feeds high fat homomethionin feedstuff (formula: cholesterol every day 1.25%, propylthiouracil 0.2%, sodium cholate 0.5%, Adeps Sus domestica 12.0%, methionine 3%, normal diet 83.05%).4 All rats are carried out blood pressure detecting, and take a blood sample survey blood fat and HCY, to confirm hypertension, hyperlipemia height HCY model modeling by Zhou Hou Success.
2, it is grouped and is administered: taking above-mentioned modeling success rat 60, being randomly divided into 8 groups (often groups 10), by being administered difference It is divided into model group, Rosuvastatin+amlodipine+aspirin+folic acid (0.5+0.125+3.75+0.04) mg/kg group, Rui Shu Cut down statin+amlodipine+aspirin+folic acid (1+0.25+7.5+0.08) mg/kg group, Rosuvastatin+amlodipine+Ah Department woods+folic acid (2+0.5+15+0.16) mg/kg group, Rosuvastatin+aspirin+folic acid (1+7.5+0.08) mg/kg Group, Rosuvastatin+aspirin (1+7.5) mg/kg group, separately have a sham operated rats, totally 7 groups.When other group gastric infusion, false Operation group and model group rats give respective volume solvent gavage.In experimentation, in addition to rats in sham-operated group feeds normal diet, Remaining is respectively organized rat and continues to feed high fat homomethionin feedstuff.Weigh weekly once for each group, adjust dosage according to body weight, give continuously Medicine 12 weeks.
3, Testing index: (1) blood pressure determination detects rat blood pressure after being administered 12 weeks；(2) kidney index determining is administered 12 weeks After, take hematometry α 1-microglobulin (α 1-MG), microdose urine protein (MALB) and serum creatinine, urine creatine, creatinine clearance rate； (3) serum homocysteine takes blood after measuring and being administered 12 weeks, measures serum homocysteine level according to test kit description.
4, statistical method: measurement data is usedRepresenting, data statistics processes and uses SPSS13.0 statistical package, and two Mean compares employing t inspection, compares employing variance analysis between many groups.
5, result:
(1) Rosuvastatin+amlodipine+aspirin+folic acid on rats blood pressure affected for the 12nd weekend, with model group Relatively, Rosuvastatin+amlodipine+aspirin+folic acid variant dosage ratio group rat blood pressure all significantly reduces, ammonia chlorine Reduce more notable when Horizon share with atorvastatin and aspirin, and dose-effect relationship is obvious；And Rosuvastatin+Ah Si Woods+folic acid group, Rosuvastatin+aspirin group rat blood pressure level does not has significant change.It is shown in Table 5.
Table 5 Rosuvastatins+amlodipine+aspirin+folic acid on hypertension companion hyperlipemia rat blood pressure impact (N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。
(2) impact of Rosuvastatin+amlodipine+aspirin+folic acid on rats renal function is compared with sham operated rats, Model group α 1 microglobulin and microdose urine protein are significantly raised, compared with model group, and Rosuvastatin+amlodipine+Ah Si Woods+folic acid respectively mates dosage group α 1 microglobulin and microdose urine protein reduces, and Rosuvastatin+aspirin+folic acid Group, Rosuvastatin+aspirin group and model group, without significant difference, are shown in Table 6；Model group creatinine clearance rate is remarkably decreased, auspicious Relax and cut down statin+amlodipine+aspirin+folic acid and respectively mate dosage group creatinine clearance rate and raised, and Rosuvastatin+Ah A department's woods+folic acid group, Rosuvastatin+aspirin group without significant difference, are shown in Table 7 with model group.
Table 6 Rosuvastatins+amlodipine+aspirin+folic acid on hypertension companion hyperlipemia rat renal function impact (N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。
Table 7 Rosuvastatins+amlodipine+aspirin+folic acid on hypertension companion hyperlipemia rat renal function impact (N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。
(2) impact of Rosuvastatin+amlodipine+aspirin+folic acid on rats serum homocysteine and sham operated rats ratio Relatively, model group HCY is significantly raised, and compared with model group, Rosuvastatin+amlodipine+aspirin+folic acid respectively mates dosage Group, Rosuvastatin+aspirin+folic acid group HCY substantially reduce, and Rosuvastatin+aspirin group is without significant difference, table Bright folic acid has significantly reduction HCY effect, and there is a certain amount effect dependency, is shown in Table 8.
The impact on hypertension companion's hyperlipemia rat serum homocysteine of the table 8 Rosuvastatins+amlodipine+aspirin+folic acid (N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。
Embodiment 9: the impact of Rosuvastatin+enalapril+aspirin+folic acid on rats Endothelium Protective effect
1, modeling: SHR rat 70, WKY rat 10,5-6 week old, male and female half and half, body weight 130～160g, 10 WKY Rat makees normal group, feeds normal diet, and remaining rat feeds high fat homomethionin feedstuff (formula: cholesterol 1%, propylthio every day Oxygen pyrimidine 0.2%, sodium cholate 0.5%, Adeps Sus domestica 12.0%, methionine 3%, normal diet 83.3%).After 4 weeks, to all rats Carry out blood pressure detecting, and take a blood sample survey blood fat and HCY, to confirm hypertension, hyperlipemia height HCY model modeling success.
2, it is grouped and is administered: taking above-mentioned modeling success rat 60, being randomly divided into 6 groups (often groups 10), by being administered difference It is divided into model group, Rosuvastatin+enalapril+aspirin+folic acid (0.5+0.5+7.5+0.08) mg/kg group, Rui Shu to cut down Statin+enalapril+aspirin+folic acid (1+1+7.5+0.08) mg/kg group, Rosuvastatin+enalapril+aspirin + folic acid (2+2+7.5+0.08) mg/kg group, Rosuvastatin+enalapril+folic acid (1+1+0.08) mg/kg group, aspirin + folic acid (7.5+0.08mg/kg) group, separately has a normal group, totally 7 groups.When other group gastric infusion, normal group and model group rats Give respective volume solvent gavage.In experimentation, in addition to normal rats feeds normal diet, remaining is respectively organized rat and continues to feed height Fat homomethionin feedstuff.Weigh weekly once for each group, adjust dosage, successive administration 12 weeks according to body weight.
3, Testing index: (1) blood pressure determination detects rat blood pressure after being administered 12 weeks；(2) protection of ecs index determining, is administered After 12 weeks, take hematometry Endothelin (ET-1), nitric oxide (NO), thromboxane (TXB2), 6-ketone prostaglandin (6-k- PGF1a)。
4, statistical method: measurement data is usedRepresenting, data statistics processes and uses SPSS10.0 statistical package, and two Mean compares employing t inspection, compares employing variance analysis between many groups.
Result:
(1) Rosuvastatin+enalapril+aspirin+folic acid on rats blood pressure affected for the 12nd weekend, with model group Relatively, Rosuvastatin+enalapril+aspirin+folic acid variant dosage ratio group, Rosuvastatin+enalapril+leaf Acid group rat blood pressure all significantly reduces, and reduces more notable when enalapril share with Rosuvastatin and aspirin；And Ah Si Woods+folic acid group rat blood pressure level does not has significant change.It is shown in Table 9.
Table 9 Rosuvastatins+enalapril+aspirin+folic acid on hypertension companion hyperlipemia rat blood pressure impact (N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。
(2) impact of Rosuvastatin+enalapril+aspirin+folic acid on rats protection of ecs function is administered 12 weeks, Comparing with normal group, model group rats serum NO level level significantly reduces, and ET-1 level significantly raises.Compare with model group, Rui Shu Cut down statin+enalapril+aspirin+folic acid variant dosage ratio group, Rosuvastatin+enalapril+equal energy of folic acid group Significance raises rat blood serum NO level and reduces ET-1 level.Test result indicate that: hypertension complicated with hyperlipemia rat occurs Significantly inner skin cell function reduces, and Rosuvastatin, enalapril, aspirin, folic acid on rats inner skin cell function have Protected effect, the protective effect of the compound preparation Human Umbilical Vein Endothelial Cells of several persons is obviously enhanced.Be shown in Table 10, table 11.
Hypertension is accompanied hyperlipemia rat protection of ecs function by table 10 Rosuvastatins+enalapril+aspirin+folic acid Impact (N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。
Hypertension is accompanied hyperlipemia rat protection of ecs function by table 11 Rosuvastatins+enalapril+aspirin+folic acid Impact (N=10)
Model group compares with normal group,#P < 0.05,##P<0.01；Administration group compares with model group,*P<0.05；**P< 0.01；Tetrad compound recipe group compares with three compound recipe groups,△P<0.05,△△P<0.01；Compare with bigeminy compound recipe group,☆P<0.05,☆☆P <0.01。

Claims (10)

1. a pharmaceutical composition, including:
(1) medicinal content selected from angiotensin receptor antagonist, angiotensin-convertion enzyme inhibitor, calcium channel blocking The one of the depressor of agent, beta-adrenoceptor antagonists or diuretic；
(2) one in hydroxyl first glutaryl coenzyme A (HMG-CoA) reductase inhibitor of medicinal content；
(3) aspirin of medicinal content；
(4) folic acid of medicinal content or 5-methyltetrahydrofolate；With
(5) acceptable carrier on pharmaceutics.
2. the pharmaceutical composition described in claim 1, it is characterised in that: described angiotensin receptor antagonist includes that chlorine is husky Smooth, valsartan, irbesartan, telmisartan, Candesartan；Angiotensin-convertion enzyme inhibitor includes captopril, according to that Puli, benazepril, lisinopril, ramipril, fosinopril, cilazapril, perindopril；Beta-receptor antagonist includes general Naphthalene Luo Er, metoprolol, atenolol, betaxolol, bisoprolol, Carvedilol, labetalol；Diuretic includes esodrix Piperazine, chlorothiazide, spironolactone, triamterene, amiloride, furosemide, indapamide；Calcium ion channel blocker includes nitre benzene ground Flat, nicardipine, nitrendipine, felodipine, amlodipine, lacidipine, lercanidipine.
3. the pharmaceutical composition described in claim 1, it is characterised in that: described HMG-CoA reductase inhibitor includes atropic Cut down statin, simvastatin, Pitavastatin, pravastatin, lovastatin, fluvastatin, cerivastatin, Rosuvastatin, she Cutting down statin, itavastatin, bervastatin, mevastatin, wherein, atorvastatin content is 5mg～80mg, simvastatin content For 5mg～80mg, Pitavastatin content be 1mg～4mg, lovastatin content be 5mg～80mg, fluvastatin content be 5mg ～80mg, pravastatin content be 5mg～80mg, Rosuvastatin content be 5mg～80mg.
4. the pharmaceutical composition described in claim 1, it is characterised in that: the medicinal content of described aspirin be 50mg～ 325mg。
5. the pharmaceutical composition described in claim 4, it is characterised in that: the medicinal content of folic acid or 5-methyltetrahydrofolate is 0.2mg～2.0mg.
6. the pharmaceutical composition according to any one of Claims 1 to 5, it is characterised in that: the pharmacy agent of described pharmaceutical composition Type is tablet, capsule or granule.
7. the pharmaceutical composition according to any one of claim 1～6 is used for blood pressure lowering and blood fat reducing in preparation, prevents or delay Purposes in atherosclerotic medicine.
Purposes the most according to claim 7, it is characterised in that: aforementioned pharmaceutical compositions is used for preventing in preparation, treat or Delaying the purposes in the medicine of target organ damage that hypertension companion's dyslipidemia causes, wherein hypertension companion dyslipidemia causes Target organ damage, moves including apoplexy, atherosclerosis, coronary heart disease, left ventricular hypertrophy, angina pectoris, myocardial infarction, acute coronary Arteries and veins syndrome, Heart function fails, benign arteriolar nephrosclerosis disease, heart failure, arrhythmia, primary cardiac all standing, kidney Hypofunction, pernicious arteriolar nephrosclerosis, peripheral arterial disease, retinal arteriosclerosis or Hypertensive Fundus pathological changes.
Purposes the most according to claim 8, it is characterised in that: the target organ damage that described atherosclerosis causes, bag Include cerebral arteriosclerosis, apoplexy, coronary heart diseases and angina pectoris, myocardial infarction, acute coronary syndrome, glomerulosclerosis Disease, peripheral arterial disease.
10. the pharmaceutical composition according to any one of Claims 1 to 5 is used for reducing the medicine of cardiocerebrovasculaevents events risk in preparation Purposes in thing.
CN201610345869.9A 2016-05-23 2016-05-23 Pharmaceutical composition for preventing cardiovascular diseases Pending CN106310274A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1785196A (en) * 2004-12-10 2006-06-14 张鹏 Compounding prepn. for treating and preventing cardiovascular or cerebrovascular diseases
CN101721413A (en) * 2008-10-13 2010-06-09 北京奥萨医药研究中心有限公司 Pharmaceutical composition for preventing and curing metabolic syndrome and application thereof
US20130210778A1 (en) * 2000-04-10 2013-08-15 Nicholas J. Wald Formulation for the prevention of cardiovascular disease

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130210778A1 (en) * 2000-04-10 2013-08-15 Nicholas J. Wald Formulation for the prevention of cardiovascular disease
CN1785196A (en) * 2004-12-10 2006-06-14 张鹏 Compounding prepn. for treating and preventing cardiovascular or cerebrovascular diseases
CN101721413A (en) * 2008-10-13 2010-06-09 北京奥萨医药研究中心有限公司 Pharmaceutical composition for preventing and curing metabolic syndrome and application thereof

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