CN101229372A - A kind of pharmaceutical composition for treating hypertension - Google Patents

Abstract

The invention provides a pharmaceutical composition for treating hypertension and its preparation. The pharmaceutical composition includes antihypertensive drugs, HMGCoA reductase inhibitors and insulin sensitizers. The pharmaceutical composition of the invention not only can effectively reduce blood pressure, but also has good prevention and treatment effects on hypertension complications. The long-term survival rate of patients has been significantly improved.

Description

A kind of pharmaceutical composition for treating hypertension

Technical field

The invention is a pharmaceutical composition for treating hypertension.

Background technique

People with high blood pressure have increasingly become a major health killer for modern urbanites, and we must pay attention to it. Hypertension mainly damages the human blood. It can promote the hardening of the arterial wall and the narrowing of the lumen-that is, "arteriosclerosis" as it is usually called. If hypertension is combined with diabetes, it will accelerate and aggravate the damage of blood vessels and make the condition worsen rapidly. It should be actively treated.

At present, there are many drugs for the treatment of hypertension. What they have in common is that they can all lower blood pressure. The difference is that the mechanism of action and links are different, and the therapeutic effects on hypertension caused by different reasons are different. Some antihypertensive drugs have protective effects on target organs, while others do not have organ protective effects, and even aggravate organ damage while lowering blood pressure. ACEI (Angiotensin-Converting Enzyme Inhibitor) can mildly and persistently reduce blood pressure, and at the same time has a good protective effect on target organs. Angiotensin II receptor antagonist (ARB) is a good substitute for ACEI drugs, with less adverse reactions, mild and stable antihypertensive effect, and better effect, but it also has slow onset and poor curative effect on severe hypertension And other issues. Calcium antagonists have a high degree of vascular selectivity, dilate coronary arteries, improve collateral circulation, and last for a long time. When used alone, some varieties are likely to cause reflex tachycardia in the treatment of refractory hypertension.

In the past, the medical field focused on the development of antihypertensive drugs in the prevention and treatment of cardiovascular diseases, and many effective antihypertensive drugs have been invented successively. But along with the continuous development of medical science, people realize that the high content of cholesterol and fat is the basic cause of cardiovascular disease, and hyperlipidemia is the main risk factor of coronary heart disease and hypertension. Therefore, people began to focus on the development of blood lipid regulating drugs as the prevention and treatment of cardiovascular diseases. Since the late 1980s, a large number of blood lipid-lowering drugs have been launched, among which HMGCoA reductase inhibitors have been well received by people, and their clinical efficacy is unmatched by other types of blood lipid regulating drugs.

In the past two years, Chinese doctors have gradually changed the way of diuresis and dilation of blood vessels to treat high blood pressure, and introduced a new way of thinking to treat this type of disease mainly by lowering blood lipids with the treatment of cardiovascular and cerebrovascular diseases. Chinese Journal of Misdiagnosis, Vol. 6, No. 17, 2006 Liu Qingyan, Yan Shiqin "Observation on the Curative Effect of Antihypertensive Combined Lipid Regulation in the Treatment of Essential Hypertension" The combination of antihypertensive drugs and simvastatin in the treatment of hypertension has achieved certain effects . However, antihypertensive drugs and HMGCoA reductase inhibitors are used in combination to treat hypertension, and the antihypertensive effect and reduction of side effects are not very satisfactory. HMGCoA reductase inhibitors include lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin, Pitavastatin or cerivastatin, etc.

Insulin sensitizers have been used for the treatment of type 2 diabetes. The current insulin sensitizers are mainly thiazolidinediones, including pioglitazone, rosiglitazone, and ciglitazone ( giglitazone), englitazonne, etc.

With the continuous development of modern medicine, the concept of hypertension treatment is also constantly developing and changing. The treatment of hypertension is not limited to antihypertensive treatment. Effective prevention and treatment of a series of complications caused by hypertension is hypertension. More important aspects of treatment. Now for the treatment of hypertension, it is more important to improve the long-term survival rate of patients. Otherwise, the blood pressure will be lowered, and the survival rate of hypertensive patients cannot be improved or even reduced, which also makes blood pressure reduction. Treatment has lost its most fundamental meaning. It can be said that among the existing antihypertensive drugs, there is no ideal drug that meets the current concept of hypertension treatment.

Contents of the invention

The invention provides a new pharmaceutical composition for treating hypertension, which contains antihypertensive drug, HMGCoA reductase inhibitor and insulin sensitizer.

The antihypertensive drug is one or more of calcium antagonists, angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists. Calcium antagonists include nifedipine, amlodipine, nicardipine, felodipine, lacidipine, nitrendipine, nimodipine Dipine (nimodipine), nifedipine (nifedipine) and the like. Angiotensin-converting enzyme inhibitors include enalapril, benazepril, fosinopril, cilagapril, perindopril, midazolam imidapril, quinapril, captopril, lisinopril, ramipril, benazepril, delapril (delapril) and so on. Angiotensin II receptor antagonists include valsartan, irbesartan, telmisartan, candesartan cilexetil, olmesartan medoxomil , Losartan (lossartan) etc.

Lunan Pharmaceutical Co., Ltd. has creatively introduced insulin sensitizers for the treatment of diabetes into the existing antihypertensive regimen based on the latest clinical research progress on hypertension treatment and the disease development trend of hypertensive patients, and has made great achievements. Good therapeutic effects, especially in the treatment of various cardiovascular and cerebrovascular complications caused by hypertension, have achieved good synergy and unexpected effects. From Example 11 and Example 12, it can be seen that the present invention has quite obvious advantages in reducing blood pressure compared with the existing antihypertensive drug + HMGCoA reductase inhibitor. In addition, cardiovascular disease is a high-incidence disease in hypertensive patients, and the present invention can effectively control the occurrence of cardiovascular disease. In Example 12 and Example 13, we demonstrated its advantages in preventing and treating cardiovascular diseases by measuring the hypertrophy index of the myocardial hypertrophy in spontaneously hypertensive rats. Thereby we have sufficient reason and basis to predict, after the present invention is used in the clinical treatment of hypertension in the future, for the death of coronary heart disease patient, non-fatal myocardial infarction incidence rate resuscitated cardiac arrest and fatal and non-fatal cerebral apoplexy rates are significantly lower.

The general antihypertensive drugs are only in pursuit of effective antihypertensive drugs, while ignoring the long-term survival rate of hypertensive patients, which makes the treatment of hypertension lose its most fundamental significance.

The advantage of composition of the present invention is embodied in following aspects:

1. The combined application of ACEI (angiotensin-converting enzyme inhibitor) or angiotensin II receptor antagonist (ARB) or calcium antagonist (CCB) with HMGCoA reductase inhibitor and insulin sensitizer has a good synergistic effect on reducing pressure effect.

Two, the side effect of the present invention is very little. Since the pharmaceutical composition of the present invention uses three antihypertensive drugs in combination, it achieves a significant synergistic effect on the antihypertensive aspect, and the dosage of the drug is significantly reduced, so that the incidence and degree of adverse reactions are significantly reduced.

3. Long-term use of the composition of the present invention has a beneficial effect on the long-term survival rate of hypertensive patients and has a positive impact on the prognosis of patients. This is also the most meaningful clinical treatment problem solved by the present invention. General antihypertensive drugs do not have a good preventive and therapeutic effect on complications such as stroke, kidney damage, and coronary heart disease caused by hypertension. The present invention aims at these deficiencies of the existing antihypertensive drugs, and through the combination of drugs, it not only produces a good synergistic effect on the antihypertensive aspect, but also produces an unexpected preventive effect on hypertension complications.

Four, the scope of application of the present invention is wide. Because of its synergistic mechanism, the present invention is suitable for various types of hypertensive patients, especially for stroke-type hypertensive patients and hypertensive patients with kidney damage. In addition, it has a good effect on hypertension combined with coronary heart disease, angina pectoris, peripheral vascular disease, elderly hypertension, gestational hypertension, and refractory hypertension.

According to the properties of the medicine and the needs of patients for convenient administration, we prepare the pharmaceutical composition of the present invention into solid pharmaceutical preparations, such as tablets, capsules, granules, pills, dripping pills and the like. Tablets include ordinary tablets, dispersible tablets, sustained-release tablets, etc., and we choose sustained-release tablets as the preferred dosage form.

The solid pharmaceutical preparation adopted by the present invention has the advantages of being convenient to carry and use, and the route of administration is simple and easy to implement, and is easy to be accepted by patients.

We have prepared the pharmaceutical composition of the present invention into sustained-release tablets in combination with the needs of patients with hypertension, which can efficiently and safely regulate blood pressure, release slowly to maintain a relatively stable blood drug concentration and a longer action time, and have the advantages of reducing toxic and side effects. Small size and more convenient to take.

Sustained-release tablets in the present invention take cellulose derivatives or vinyl polymers as sustained-release matrices, and these sustained-release matrices can be methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose One or more of cellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, and acrylic resin.

specific embodiment

Now further illustrate content of the present invention by following examples, but the scope of application of the present invention is not limited to following examples.

Embodiment 1 hypertension compound tablet

Simvastatin 20g

Amlodipine 2.5g

Pioglitazone 20g

The rest of the pharmaceutical excipients are commonly used excipients for preparing tablets.

Preparation process: Prepared according to the conventional preparation process of photographic agent.

Embodiment 2 Hypertension Compound Capsules

Atorvastatin 10g

Enalapril 10g

Piroglitazone 20g

All the other pharmaceutical excipients are commonly used excipients for preparing capsules.

Preparation process: It is prepared according to the conventional preparation process of capsules.

Embodiment 3 hypertensive compound bilayer tablet

Simvastatin 10g

Mannitol 10g

Lactose 40g

Microcrystalline Cellulose 20g

6% PVP in 95% ethanol solution 120g

Magnesium Stearate 2g

Preparation process: Simvastatin passes through a 100-mesh sieve, mannitol, lactose, and microcrystalline cellulose pass through a 80-mesh sieve, weighs the prescribed amount of niacin and mixes them evenly with mannitol, lactose, and microcrystalline cellulose, and adds 6% PVP Appropriate amount of 95% ethanol solution is granulated, dried at 60° C., sieved with 16 meshes to dry the granules, and adding the prescribed amount of magnesium stearate to the dry granules.

Nifedipine 30g

Rosiglitazone 8g

Pregelatinized starch 50g

Mannitol 50g

95% ethanol solution of 6% PVP 100g

Micropowder silica gel 5g

Preparation process: Nifedipine and rosiglitazone pass through a 100-mesh sieve, pregelatinized starch and mannitol pass through a 80-mesh sieve, weigh the prescribed amount of nifedipine, rosiglitazone, pregelatinized starch and mannitol and mix Uniformly, add 6% PVP in 95% ethanol solution in an appropriate amount to granulate, dry at 60°C, sieve the dry granules with a 16-mesh sieve, and add the prescribed amount of magnesium stearate to the dry granules.

The above two components are punched with a double-layer tablet press to obtain a double-layer tablet.

Embodiment 4 hypertension compound dispersible tablet

Lovastatin 20g

Captopril 30g

Rosiglitazone 4g

Carboxymethylcellulose Calcium 15g

Cross-linked polyvinylpyrrolidone 15g

Microcrystalline Cellulose 140g

10% starch slurry Appropriate amount

Magnesium stearate 6g

Preparation Process:

Pass the prescribed amount of lovastatin, captopril and rosiglitazone through a 100-mesh sieve, carboxymethylcellulose calcium, cross-linked polyvinylpyrrolidone, and microcrystalline cellulose through a 80-mesh sieve, mix well and add an appropriate amount of 10% The starch slurry is granulated, and after adding magnesium stearate, it can be compressed into tablets.

Embodiment 5 hypertension compound granule

Pravastatin 10g

Amlodipine 5g

Pioglitazone 20g

The rest of the pharmaceutical excipients are commonly used excipients for preparing granules.

Preparation process: Prepare according to the conventional preparation process of granules.

Embodiment 6 hypertension compound tablet

Simvastatin 20g

Nicardipine 60g

Pioglitazone 10g

The rest of the pharmaceutical excipients are commonly used excipients for preparing tablets.

Preparation process: Prepared according to the conventional preparation process of photographic agent.

Embodiment 7 Hypertension Compound Sustained-release Tablets

Simvastatin 10g

Amlodipine 5g

Pioglitazone 20g

Hypromellose 3-80g

Polyvinylpyrrolidone 1-100g

Lactose 5-85g

Micropowder silica gel 1-100g

Preparation process: Mix the prescription amount of simvastatin, amlodipine, piroglitazone and sustained-release agent evenly, add the binder to granulate, dry at 40°C-80°C, dry the granules, and add the prescription to the dry granules The right amount of lubricant, mix well, and punch the special-shaped tablets.

Example 8 Hypertension Compound Sustained-release Tablets

Atorvastatin 5g

Amlodipine 5g

Piroglitazone 20g

Hydroxyethylcellulose 1-100g

Microcrystalline Cellulose 1-80g

Lactose 5-85g

Magnesium stearate 1-50g

Preparation process: with embodiment 7.

Embodiment 9 Hypertension Compound Sustained-release Tablets

Atorvastatin 5g

Benazepril 10g

Rosiglitazone 4g

Carboxyethyl cellulose 1-100g

Microcrystalline Cellulose 1-80g

Polyvinylpyrrolidone 1-100g

Magnesium stearate 1-50g

Preparation process: with embodiment 7.

Embodiment 10 Hypertension Compound Sustained-release Tablets

Atorvastatin 5g

Valsartan 40g

Rosiglitazone 4g

Carboxyethyl cellulose 1-100g

Microcrystalline Cellulose 1-80g

Lactose 5-85g

Magnesium stearate 1-50g

Preparation process: with embodiment 7.

Example 11 Therapeutic effect of hypertension compound on hereditary hypertensive stroke rats (SHRsp) Animals:

SHRsp, male and female, 7 weeks old, 150-200g, test temperature (20±1)°C, humidity 40%-70%, drink 0.9% saline and eat high-protein feed during the whole test.

method:

48 7-week-old SHRsp were fed with conventional feed for 1 week, weighed and measured with a HX-I small animal blood pressure measuring instrument, and recorded with a LMS-2B two-channel physiological recorder. The conventional tail artery method was used to measure the systolic blood pressure of conscious animals, according to Blood pressure levels were randomly divided into 6 groups, 8 rats in each group. The first group is the model group, with the same volume of 0.9% saline orally; the second group is the pungent+ammonia group (simvastatin+amlodipine), 4.0mg/(kg.d) simvastatin+1.0mg/(kg .d) Amlodipine; the third is compound low-dose group (simvastatin + amlodipine + piroglitazone), 1.33mg/(kg.d) simvastatin+0.33mg/(kg.d) ammonium chloride Dipine + 1.33mg/(kg.d) pioglitazone; the fourth group is the compound medium dose group, 4.0mg/(kg.d) octane + 1.0mg/(kg.d) ammonia + 4.0mg/(kg.d) pyridoxine ; The fifth group is the compound high-dose group, 12.0mg/(kg.d) pungent+3.0mg/(kg.d) ammonia+12.0mg/(kg.d)pyridine. All groups were intragastrically administered. All animals drank 1% saline. During the experiment, the diet, survival and behavior of the animals were observed daily, the body weight was measured daily, and the dosage of drugs was adjusted according to the body weight; the blood pressure of the tail artery was measured every 2 weeks. During the 6-week experiment, the number of stroke attacks and the first attack time of animals in each group were recorded.

Experimental results

1. The effect of hypertension compound on SHRsp blood pressure

The results showed that, except the piroglitazone group, there were significant differences between the other groups and the model group. There is a significant difference between the compound middle group and compound high group and the pungent + ammonia group, indicating that the middle and high doses of simvastatin, amlodipine and piroglitazone have a good synergistic antihypertensive effect in the treatment of essential hypertension .

Table 1 The influence of hypertension compound on SHRsp blood pressure (n=8) (kPa)

与辛+氨组比较p＜0.05. ^● Compared with the model group, p<0.05,

Compared with the octyl+ammonia group, p<0.05.

2. The effect of hypertension compound on the body weight and survival of SHRsp

The results showed that SHRsp often had decreased food intake and weight loss before stroke. It can be seen from Table 2 that there was no significant difference in body weight of rats in the 6 groups at the age of 8 weeks. After administration in groups, the weight of rats in the pungent+ammonia group, the compound middle group and the compound high group continued to increase, which was significantly different from that of the model group over the same period (p<0.05 or p<0.01); the body weight of the 14-week-old compound low group was greater than Simultaneous model group (p<0.05). Moreover, with the onset of stroke, 3 SHRsp died in the model group, 1 died in the piroglitazone group, and no death occurred in the other groups. This fully shows that the hypertensive compound group, especially the compound medium group and the compound high group have a good effect on the weight loss and stroke mortality of SHRsp rats.

Table 2 Effect of Hypertensive Compound on SHRsp Body Weight and Survival (n=8) (g)

Table 2 (continued)

The data in () is the number of stroke rats survived.

3. The effect of hypertension compound on the onset of SHRsp stroke

The results showed that at the age of 14 weeks, 6 SHRsps in the model group had a stroke, 2 in the Xin + ammonia group and the compound low group, 1 in the compound group, and no stroke in the compound high group. And after each administration, the symptoms of stroke were significantly relieved, indicating that the middle compound group, especially the high compound group, has a good preventive effect on stroke attacks caused by hypertension.

Table 3 The effect of hypertension compound on the onset of SHRsp stroke (n=8)

4. Determination of carotid intima-media thickness

After the animal was anesthetized and fixed, inject Even's blue dye (60 mg/kg) through the femoral artery, and use 0.9% normal saline as the perfusion solution after 30 minutes. Perfuse with % paraformaldehyde saline for 10 minutes, and fix in situ (the pressure is the same as above). Take Even's blue-stained carotid artery segment, put it into formalin solution for further fixation, take the front, middle and back three parts for paraffin embedding, non-serial sections of 8-10 layers, and perform HE staining, and randomly take 3 blood vessel sections Input the computer image processing system to perform computer image measurement to calculate the maximum intima thickness, media thickness, and intima/media thickness ratio.

The results showed that there were significant differences in each group compared with the model group. Compared with the pungent + ammonia group, there was a significant difference in the compound low group, and there was a very significant difference in the compound middle group and the compound high group. It shows that simvastatin, amlodipine and piroglitazone have a good synergistic effect on carotid intima-media thickness in spontaneously hypertensive rats.

Table 4 Effect of Hypertensive Compound on Intima-media Thickness in Spontaneously Hypertensive Rats

^● Compared with the model group, p<0.05, ^●● Compared with the model group, p<0.01;

与辛+氨组比较p＜0.05，与辛+氨组比较p＜0.01.

p<0.05 compared with octyl + ammonia group, Compared with the octyl + ammonia group, p<0.01.

Example 12 Therapeutic Effect of Hypertension Compound on Spontaneously Hypertensive Rats

Animals and Experimental Methods

Spontaneously hypertensive rats (300±5g) were randomly divided into 6 groups (n=8), i.e. the first group was the model group, and the same volume of 1% saline was administered orally; atorvastatin + benazepril), 2.5mg/(kg.d) atorvastatin+2.5mg/(kg.d) benazepril; the third group is rosiglitazone group, 1.0mg/( kg.d) Luo; the fourth group is compound low group (atorvastatin + benazepril + rosiglitazone), 0.83mg/(kg.d) atrop + 0.83mg/(kg.d) shellfish +0.33mg/(kg.d) Luo; the fifth group is the compound middle group, 2.5mg/(kg.d) Ato+2.5mg/(kg.d) Bei+1.0mg/(kg.d) Luo; Group 6 is compound high group, 7.5mg/(kg.d) Atrop+7.5mg/(kg.d) shellfish+3.0mg/(kg.d) Luo, each group is administered by intragastric administration.

Experimental results

1. Effects of Hypertensive Compound on Blood Pressure in Spontaneously Hypertensive Rats

The results showed that, except the rosiglitazone group, there were significant differences between the other groups and the model group. There is a significant difference between the compound group and the Atuo+Bei group, and there is a very significant difference between the compound medium group and the compound high group and the Atuo+Bei group. It shows that the combination of atorvastatin, benazepril and rosiglitazone has a good synergistic effect on the antihypertensive effect of spontaneously hypertensive rats.

The influence of table 5 hypertension compound on the blood pressure of spontaneously hypertensive rats (n=8) (kPa)

^● Compared with the model group, p<0.05, ^●● Compared with the model group, p<0.01;

与阿托+贝组比较p＜0.05，

与阿托+贝组比较p＜0.01.

p<0.05 compared with Ato + Bei group,

Compared with the Ato + Bei group, p<0.01.

2. Determination of heart weight, left ventricle weight, body weight and left ventricle hypertrophy index (left ventricle weight/body weight): after killing the rats with 10% potassium chloride (2mmol/L, 1ml/only), measure the body weight, take out the heart, remove The large blood vessels and connective tissue outside the heart were rinsed, absorbed by filter paper, and the heart was weighed; the atrium was removed and the left ventricle was weighed, and the ratio of left ventricle weight to body weight was calculated.

The results showed that, except the rosiglitazone group, there were significant differences between the other groups and the model group. There is a significant difference between the compound group and the Atuo+Bei group, and there is a very significant difference between the compound medium group and the compound high group and the Atuo+Bei group. It shows that the compound of atorvastatin, benazepril and rosiglitazone has a good synergistic effect on the treatment of myocardial hypertrophy in spontaneously hypertensive rats.

Table 6 Effect of Hypertensive Compound on Myocardial Hypertrophy in Spontaneously Hypertensive Rats (n=8) (g)

^● Compared with the model group, p<0.05, ^●● Compared with the model group, p<0.01.

与阿托+贝组比较p＜0.05，

与阿托+贝组比较p＜0.01.

p<0.05 compared with Ato + Bei group,

Compared with the Ato + Bei group, p<0.01.

3. Determination of microalbumin in urine:

Reagent: 1. 10% (v/v) glacial acetic acid solution (PH2.8).

2. 0.303mol/L glycine-glacial acetic acid buffer solution (PH3.0): Weigh 22.72g glycine, dilute it with 10% glacial acetic acid solution to 1000ml, add NaN ₃ 100mg, and seal it at room temperature to be stable for 1 year.

3. Bromophenol blue (1.924mmol/L) stock solution: Accurately weigh 257.36mg of BPB, dissolve it with absolute ethanol to 200ml, and it can be stable for 1 year in a 4°C refrigerator.

4. Bromophenol blue (0.231mmol/L) developer: take 60ml BPB stock solution, add 2.5ml Triton X-100,

Dilute to 500ml with glycine-glacial acetic acid buffer solution, and keep sealed at room temperature for 1 year.

Collection and detection of specimens: At the 4th, 8th, 12th and 16th week, the rats were raised in metabolic cages, and the urine was collected overnight for 12 hours, and the urine volume was accurately recorded. Take 4ml, after treatment with sodium azide, centrifuge (2000r/min) for 10min, take the supernatant and store it in a -20°C refrigerator to store the urine albumin to be tested. Measure 2ml of stored rat urine, add 1ml of chromogen each, mix well (to prevent bubbles), and measure the absorbance A at 600nm with a UV spectrophotometer.

The results showed that there were significant differences between each group and the model group. There are extremely significant differences between the compound medium group and compound high group and the Atuo+Bei group. It shows that the combination of atorvastatin, benazepril and rosiglitazone has a good synergistic effect on the urinary microalbumin in spontaneously hypertensive rats.

Table 7 Effect of Hypertensive Compound on Urinary Microalbumin in Spontaneously Hypertensive Rats

^● Compared with the model group, p<0.05, ^●● Compared with the model group, p<0.01.

与阿托+贝组比较p＜0.01. p<0.05 compared with Ato + Bei group,

Compared with the Ato + Bei group, p<0.01.

4. Determination of carotid intima-media thickness

Experimental method is the same as embodiment 11

The results showed that there were significant differences in each group compared with the model group. Compared with the Atuo+Bei group, there was a significant difference in the compound low group, and there was a very significant difference in the compound medium group and the compound high group. It shows that atorvastatin, benazepril and rosiglitazone have a good synergistic effect on carotid intima-media thickness in spontaneously hypertensive rats.

Table 8 Effects of Hypertensive Compound on Intima-media Thickness in Spontaneously Hypertensive Rats (n=8)

^● Compared with the model group, p<0.05, ^●● Compared with the model group, p<0.01;

与阿托+贝组比较p＜0.05，

与阿托+贝组比较p＜0.01.

p<0.05 compared with Ato + Bei group,

Compared with the Ato + Bei group, p<0.01.

Example 13

Spontaneously hypertensive rats (300 ± 5g) were randomly divided into 6 groups (n=8), i.e. the first group was the model group, and the same volume of 1% saline was administered orally; the second group was the Rosu+Valerian group (Rosu Suvastatin+valsartan), 1.0mg/(kg.d) rosuvastatin+15mg/(kg.d) valsartan; the third group is rosiglitazone group, 1.0mg/(kg.d) ) Luo; the fourth group is compound low group (rosuvastatin + valsartan + rosiglitazone), 0.33mg/(kg.d) rosu+5mg/(kg.d) valerian+0.33mg/( kg.d) luo; the fifth group is compound middle group, 1.0mg/(kg.d) rosu + 15mg/(kg.d) valerian + 1.0mg/(kg.d) luo; the sixth group is compound high group, 3.0mg/(kg.d) rosu+45mg/(kg.d) valerian+3.0mg/(kg.d) Luo, each group was administered by intragastric administration.

Effect of Hypertension Compound on Myocardial Hypertrophy in Spontaneously Hypertensive Rats (SHR)

The experimental method is the same as in Example 12.

The results showed that, except the rosiglitazone group, there were significant differences between the other groups and the model group. There is a significant difference between the compound group and the rosu + valerian group, and there is a very significant difference between the compound medium group and the compound high group and the rosu + valerian group. It shows that rosuvastatin, valsartan and rosiglitazone have a good synergistic effect on the treatment of myocardial hypertrophy in spontaneously hypertensive rats.

Table 9 Effects of Hypertensive Compound on Myocardial Hypertrophy in Spontaneously Hypertensive Rats (n=8) (g)

^● Compared with the model group, p<0.05, ^●● Compared with the model group, p<0.01.

与罗苏+缬组比较p＜0.01. Compared with Rosu + Valerian group, p<0.05,

Compared with Rosu + Valerian group, p<0.01.

In addition, it can also achieve good synergistic effects on blood pressure, urinary microalbumin and carotid artery intima-media thickness in spontaneously hypertensive rats.

In Example 11, 12 and 13, simvastatin, atorvastatin and rosuvastatin can be replaced by other statins such as: lovastatin, pravastatin, fluvastatin, pitavastatin or simvastatin replaced. Both piroglitazone and rosiglitazone can be replaced by other thiazolidinedione hypoglycemic agents: ciglitazone, emglitazone, etc. Amlodipine, benazepril, and valsartan can be used by other antihypertensive drugs Calcium antagonists: nifedipine, nicardipine, felodipine, lacidipine, nitrendipine, nimodipine, nifludipine Equality; angiotensin-converting enzyme inhibitors: enalapril, fosinopril, cilazapril, perindopril, imidapril, quinapril, captopril, lisinopril, Ramipril, Benazepril, Delapril; Angiotensin II receptor antagonists: Irbesartan, Telmisartan, Candesartan Medoxomil, Olmesartan Medoxomil, Losartan etc. substitute. The above substitutions are all scientific and reasonable, and the same good synergistic effect has been obtained by testing the indicators in Examples 11, 12, and 13.

Claims (13)

1. A pharmaceutical composition for treating hypertension, characterized in that it contains hypotensive drugs, HMGCoA reductase inhibitors and insulin sensitizers. 2. The pharmaceutical composition according to claim 1, wherein the antihypertensive drug is one or more of calcium antagonists, angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists. kind. 3. The pharmaceutical composition according to claim 2, wherein said calcium ion antagonist is nifedipine, amlodipine, nicardipine, felodipine, lacidipine, nitrendipine, nimodipine Dipine, Nifludipine. 4. The pharmaceutical composition according to claim 2, wherein said angiotensin-converting enzyme inhibitor is enalapril, benazepril, fosinopril, cilazapril, perindopril , imidapril, quinapril, captopril, lisinopril, ramipril, benazepril, delapril. 5. the pharmaceutical composition as claimed in claim 2 is characterized in that described angiotensin II receptor antagonist is valsartan, irbesartan, telmisartan, candesartan cilexetil, omesart Tan cilexetil, losartan. 6. The pharmaceutical composition according to claim 1, wherein said HMGCoA reductase inhibitor is lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin One or more of , pitavastatin or simvastatin. 7. The pharmaceutical composition according to claim 1, characterized in that the HMGCoA reductase inhibitor is one or more of simvastatin, atorvastatin or rosuvastatin. 8. The pharmaceutical composition according to claim 1, wherein the insulin sensitizer is any one or more of piroglitazone, rosiglitazone, ciglitazone, and emglitazone . 9. The pharmaceutical composition according to claim 1, characterized in that the insulin sensitizer is piroglitazone and ciglitazone. 10. The pharmaceutical composition according to claim 1, characterized in that it is tablet, capsule, granule, pill or drop pill. 11. The pharmaceutical composition according to claim 5, characterized in that the tablet is a common tablet, a dispersible tablet or a sustained-release tablet. 12. The pharmaceutical composition according to claim 6, characterized in that said sustained-release tablet contains cellulose derivatives or vinyl polymers. 13. The pharmaceutical composition according to claim 1, characterized in that it also contains methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, One or more of carboxymethyl cellulose, carboxyethyl cellulose, microcellulose, starch, polyvinylpyrrolidone, and acrylic resin.