KR950007207B1 - Materials for medical treatment of hypertension - Google Patents

Abstract

The drug composition for the treatment of hypertension comprises a β1- blocking agent as a sympathetic nerve blocking agent, a β1-blocking agent, a ACE inhibitor and a diuretic. The β1-blocking agent is selected from acebutolol, atenolol, metoprolol, nanolol, propranolol, timolol, penputolol, cateolol or pindolol; the α1-blocking agent is selected from prazosin, terazosin or doxazosin; the ACE inhibitor is selected from captopril, enalapril, lisinopril or cilazapril; and the diuretic is selected from bendroflumethiazide, hydroflumethiazide, methyclothiazide, polythiazide, trichlormethiazide, chlorthalidone, indapamide, metolazone, quinethazone or cyclothiazide.

Description

Hypertension Therapeutic Composition

The present invention relates to a novel hypertension therapeutic composition.

The causes of essential hypertension have been studied extensively worldwide by numerous scholars over the last half century, but it is not yet clear, only in fragments.

Therefore, the treatment of hypertension does not know the root cause, and no curative treatment has been established, but the focus of the treatment is on blood pressure drop alone or arbitrarily combined with cross-sectional drugs.

In addition, almost all of the drugs have some side effects at the therapeutic dose, which reduces the quality of life, making it difficult to take them for a long time.

The present inventor has continued to research the cause of hypertension from 1955 to today until now. The inventor of the present invention has been advocating possession-induced theory (素 地 -induced theory) since 1958 as the etiology of essential hypertension, and has supplemented this theory until now.

In the incidence of hypertension, sympathetic nervous system superiority was claimed, and mental inducement and excessive intake of salt were pointed out. Sympathetic dominant constitutive superiority expresses overreaction of sympathetic nerve to mental stress and suppresses parasympathetic nerve function. Excessive salt intake increases blood pressure, narrows the lumen, and promotes a blood pressure-up response due to stress.

When mental stress is strong and long-acting in hypertensive predisposition, sympathetic nervous superiority, the endocrine hormonal over-release caused by several kinds of endocrine hypertension. Once developed, hypertension may result in subsequent mental stress, excessive intake of saline, organic thickening of the arterial wall due to elevated blood pressure itself, or atherosclerosis that develops from high blood pressure, or carotid sinus hardening. Due to dysfunction, blood pressure increases with increasing day.

When mental stress invades the living body, the biological biological axis of reaction is triggered. The first axis is the cerebral cortex-limbic system-hypothalamic-sympathetic nerve axis, and the other axis is the cerebral cortex-limbic system-hypothalamus-pituitary-adrenal cortex.

Initiation of the sympathetic nervous system firstly increases heart rate through the β ₁ receptor of the heart by the release of epinephrine from the adrenal medulla, thus leading to an increase in cardiac output, and secondly to norepinephrine at the sympathetic nerve endings. the reduction of peripheral blood vessels through the α ₁ receptor by the release of norepinephrine, and third, the secretion of renin by renal JG cell stimulation at the sympathetic nerve terminal, and further, angiotensin I → Angiotensin II. → The secretion of aldosterone, ie the contraction of the peripheral vestibule by angiotensin II and the release of aldosterone, leads to the storage of Na in the blood, further increasing the amount of plasma.

On the other axis, ACTH is secreted from the anterior lobe of the pituitary gland, which promotes the secretion of corticosteroids, ie aldosterone, in the adrenal cortex. This also leads to the storage of Na in the blood and thus an increase in plasma volume.

The chart sets the basic direction of hypertension therapy.

1. It is the way to block the beginning of sympathetic nerve activation in the brain center. This will be the ideal way to treat high blood pressure. These drugs include colonidibe, qu anabenz, guanfacine and methyldopa. However, since these drugs strongly block the sympathetic nerves in the center, they greatly reduce the level of life, and therefore these drugs cannot be widely used as a general treatment.

As a side effect, severe insomnia, reactive hypertension, headache, deep vein, drowsiness, bradycardia, dry mouth, fever, orthostatic hypotension, digestive disorders, colitis, inflammation, liver cirrhosis, hemolytic anemia, thrombocytopenia and hypertension Can be used as an injection.

2. Therefore, the other method is to inhibit and block the factor of blood pressure increase in the distal end. First, the reduction of cardiac output is the blockade of cardiac β ₁ receptors. These include acebutolol, acenolol, atenolol, metoprolol, nadolol, propranolol, timolol

1) Penputolol, cateolol, and pindolol. Side effects of these drugs may include bronchial asthma, obstructive pulmonary disease, heart failure, heart block, and si ck sinus syndrome, and also cause fatigue, insomnia, sexual dysfunction and elevated blood lipid levels. However, among these drugs, acebutolol is cardioselective, so it does not contract the bronchi and does not increase blood lipid because it has ISA (內因 性 交感神經 刺 戟 作用). It also does not inhibit insulin secretion. Second, prazosin, terazosin, and doxazosin mesylate may be recommended as blocking drugs for the peripheral blood vessel wall α ₁ receptor. These drugs also have side effects such as first syncope, hemorrhage, palpitations, fluid retention, headache, drowsiness, weakness, antisympathetic nerves, persistent erections, urinary incontinence, among which doxazosin has less side effects than other drugs, and plasma geography Suppresses the rise.

Fifth, the newly boosted substance uses ACE inhibitor (angiotensin convert-ing enzyme inhihitors) to block the production of angiotensin II. Others include cap topril, enalapril, lisinopril and silazapril. These side effects include hypotension, loss of appetite, rash, cough, bronchial spasms, kidney damage, jaundice, angioedema, increased blood swelling, hematopoietic disorders, miscarriage.

Among these drugs, silazapril has a longer half-life than other formulations, and captopril has less side effects and a pronounced pressure effect, and thus improves blood lipid and decreases insulin resistance, thereby preventing the diuretic synergistic effect. In addition, as a terminal vasodilator, calcium channel blockers and direct vascular wall smooth muscle glidants may be used in combination.

As a blocking agent, diltiazem, nicardipine, nif endipine, nitrendipine and verapamil can be used as side effects. Heart failure, bradycardia, breast feminization, Hypotension, heart AV block, constipation, dizziness, edema, headache.

In addition, hydralazine and minoxidil may be mentioned as direct vasodilators. Side effects of these drugs include digestive disorders, tachycardia, exacerbation of angina, headache, dizziness, fluid retention, stuffy nose, rash, hepatitis, nephritis, hair growth, thrombocytopenia, and leukopenia. Hydralage is not delicious because it causes tachycardia.

Fourth, diuretics are typical drugs that reduce blood Na retention or increase in plasma volume.

Diuretics are thiazide diuretics, bendroflumeth iazide, benzthiazide, chlorothiazide, hydrochlorothiazide, chlorothalidine, and indama It includes idpamide, metolatazone, quentahazone, and cyclothiazide. Side effects include hyperuric acid, hyperkalemia, hypoglycemia, hyperglycemia, blood Na There are side effects such as decrease, increased blood Ca, pancreatitis, rash and other allergic reactions, increased blood cholesterol and triglycerides, depression, erectile dysfunction, and loop diuretics such as bumetanide and furosemide. Side effects include dehydration, circulatory collapse, embolism, decreased blood potassium, decreased magnesium in blood, reduced blood Ca, increased blood sugar, metabolic alkalosis, increased uric acid, There are side effects such as rashes, increased blood cholesterol and triglycerides.

In addition to this, triamide (tripamide) can be used as a vitiazide type diuretic.

Potassium preservative diuretics include amiloride, spironolactone, and triamterene. Side effects include increased potassium in the blood, digestive disorders, rash, headache, blood loss, breast feminization, and granulation. It has side effects such as leukopenia, dysmenorrhea, digestive disorders, increased BUN in blood, rash, tumor development, metabolic acidosis and kidney stones in rats.

That is, all antihypertensive drugs have various side effects as described above, and in particular, side effects of sexual dysfunction have almost all drugs. Until now, in the treatment of hypertension, one or two of such fragmentary routes have been used in combination.

However, the factors that cause hypertension by stress have a path to open, as shown in the diagram, and as the practice of hypertension has been used so far, only one or two of these pathways have been used. Therefore, the side effects were severe and the hypertension patients could not lead a comfortable life, and of course, they could not bring a full therapeutic effect.

As a result of a long study, the present inventors have found that the combination of β ₁ blocker, α ₁ blocker, ACE inhibitor and diuretic, or, if necessary, a combination of a channel blocker as a sympathetic receptor blocker blocks all pathways of blood pressure increase, which is the most ideal treatment. We found a surprising fact that the amount of each of the original formulations used was 1/2 1/2 to 1/10.

Side effects of drugs can be prevented by using them as little as possible. Drugs of the four types of the present invention and calcium channel blockers are used in different action sites, and when used in combination, develops an excellent blood pressure lowering effect due to a synergistic effect, and reduces the amount of use (1/2 to 1/10). Prevent and increase tolerability.

The solid pressure therapeutic composition of the present invention has the following advantages.

First: The antihypertensive composition of the present invention can be used for all kinds of hypertension.

Secondly, the hypertension therapeutic composition of the present invention is accurate and rapid. This is because it is formulated with four types of drugs that block the onset factor of this hypertension, and because each drug has a different site of action, the synergistic effect increases the coercive effect.

Third: The hypertension therapeutic composition of the present invention has very few side effects. This is because each drug is usually formulated at a dosage of 1/2 to 1/10, so the incidence of side effects of each drug is greatly reduced.

Fourth: In the hypertension therapeutic composition of the present invention, the blood lipid synergism that diuretics generally have is offset by the unique check action of the α ₁ blocker and the ACE inhibitor.

Fifth: The antihypertensive composition of the present invention was created based on the etiology of the essential hypertension, the possession-induction theory, and is much more effective than any antihypertensive agent experienced by the present inventors in the past 30 years.

Since all of the components used in the present invention are already secured, developed as drugs, and used in clinical practice, no acute toxicity test is necessary.

Each drug used in the hypertension therapeutic composition of the present invention is a β ₁ blocker, acebutoltool 100-400mg, atenolol 12.5-25mg, metoprolol 25-50mg, nadolol 10-20mg, thymoltol 10-40mg, pindolol 5 Preference is given to using -10 mg, catelol 5-10 mg, furofranolol 20-40 mg, oxprenolol 5-50 mg, tolamolol 5-50 mg, phthalol 5-50 mg.

It is preferable to use doxazosin 0.5-4.0 mg, prazosin 0.5-1.0 mg, and terazosin 0.5-1.0 mg as the α ₁ blocker.

It is preferable to use captopril 12.5-50.0mg, enarafril 2.5-5.0mg, ripinopril 5.0-40.0mg silazapril 0.5-5.0mg as ACE inhibitors that inhibit the production of angiotensin II, and as calcium channel blockers It is preferable to use 20-120 mg, nicardipine 20-60 mg, nifedipine 10-60 mg, nirenedipine 10-20 mg, veriphil 20-120 mg, and minoxidil 5-100 mg as a vascular dilator.

As a diuretic agent used in the present invention, as a thiazide diuretic, 12.5-100 mg of hydrochlorothiazide, 12.5-50 mg of chlorodalidone, 2.5-5 mg of bendroflumezide, 12.5-50 mg of benzthiazide, and 12.5-100 mg of chlorothiazide , Hydroplumthiazide 12.5-50mg Methylclothiazide 2.5-5.0mg, Molythiazide 2-4mg, Trichloromethiazide 1-4mg, Indafaamide 2.5mg, Metorazone 0.5-1mg, Quinotazone 20-100mg It is preferable to use 1-2 mg of cyclothiazone, it is preferable to use 0.5-10 mg of bumetanide, 40-320 mg of flocemide as LOOP diuretic, and 15-30 mg of trifamide as vitiazide diuretic. .

As calcium preservative diuretics, it is preferable to use 5-10 mg of amylolide, 25-100 mg of spyronotactone, and 50-200 mg of triamterin. The prescribed amount may be increased or decreased depending on the sex, condition, progression of hypertension and other factors of the patient. In addition, the present invention, the high blood pressure therapeutic composition can be taken once to three times a day.

In the following, the present invention is explained in detail.

Example 1

(In tablet 1 tablet)

Acebutolol 100mg

Doxazosin 0.5mg

Captopril 12.5mg

Hydrochlorothiazide 12.5mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 2

(In tablet 1 tablet)

Acebutolol 200mg

Doxazosin 1mg

Captopril 25mg

Hydrochlorothiazide 25mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 3

(In tablet 1 tablet)

Acebutolol 100mg

Doxazosin 0.5mg

Captopril 12.5mg

Hydrochlorothiazide 12.5mg

Tiltiazem 15mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 4

(In tablet 1 tablet)

Acebutolol 200mg

Doxazosin 1mg

Captopril 25mg

Hydrochlorothiazide 25mg

Nifedipine 10mg

The above-mentioned main ingredient is mixed with a conventional excipient according to a conventional method for producing a tablet to prepare a tablet.

Example 5

(In tablet 1 tablet)

Acebutolol 100mg

Prazosin 0.5mg

Captopril 12.5mg

Lisinopril 10.0mg

Chlorthalytone 12.5mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 7

(In tablet 1 tablet)

Natolol 10mg

Prazosin 0.5mg

Captopril 50.0mg

Benzothiazide 50mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 8

(In tablet 1 tablet)

Timolol 20mg

Doxazosin 2.0mg

Silazapril 2.5mg

Trichloromethiazide 4.0mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 9

(In tablet 1 tablet)

Pindroll 5mg

Doxazosin 1.0mg

Infamide 2.5mg

Captopril 25.0mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 10

(In tablet 1 tablet)

Meroptolol 25.0 mg

Captopril 25.0mg

Terrazosin 0.5mg

Methiruclothiazide 2.5mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 11

(In tablet 1 tablet)

Propranolol 30.0mg

Terrazosin 0.5mg

Enalapril 2.5mg

Metolazone 0.5mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 12

(In tablet 1 tablet)

Catelol 10.0 mg

Prazosin 1.0mg

Captopril 25.0mg

Quinotazone 50.0mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 13

(In tablet 1 tablet)

Acebutolol 100mg

Doxazosin 12.5mg

Enalapril 5.0mg

Quinotazone 50.0mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main components in the conventional method for producing tablets.

Example 14

(In tablet 1 tablet)

Athenol 25.0mg

Terrazosin 1.0mg

Lisinopril 40.0mg

Chlorothalidone 12.5 mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

The hypertension therapeutic composition of the present invention can be used by adding 0.1-0.6mg of clonidiane, 8-32mg of guansbenz, and 100-1000mg of methyldopa as central sympathetic inhibitors. In addition, 10-15 mg of guanadrel, guanethidine 5-150 mg, and 0.05-0.25 mg of reserpine may be used.

Since these sympathetic inhibitors have many side effects, it is preferable to use them for the emergency patient only and not to use them for maintenance.

Example 15

(In tablet 1 tablet)

Acebutolol 100mg

Doxazosin 0.5mg

Captopril 12.5mg

Hydrochlorothiazide 12.5mg

Desser Pin 0.05mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 16

(In tablet 1 tablet)

Acebutolol 100mg

Doxazosin 0.5mg

Captopril 12.5mg

Hydrochlorothiazide 12.5mg

Clonidine 0.1mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

Example 17

(In tablet 1 tablet)

Acebutolol 100mg

Doxazosin 0.5mg

Tiltiazem 15mg

Methyldopa 100.0mg

Tablets are prepared by mixing and tableting the usual excipients according to the above-described main ingredients in the conventional method for producing tablets.

EXAMPLE (Clinical Experiment)

Hypertensive classification was associated with mild renal BP 90-10 4mmHg, 105-115 moderate, persistent 115 or more severe, and III-IV degree lesions in renal failure and fundus at 130 and above, as determined by the American Association for Hypertension Research. Hypoxia was defined as malignant hypertension.

The hypertension therapeutic composition of the present invention has been found to have an excellent blood pressure strengthening effect, almost no side effects. The results are shown in the table below.

Experimental Example 1

Mild hypertension (41 years old, female)

Pretreatment Blood Pressure: 160/100

Treatment method: After the oral administration of the composition of Example 1 for 3 days orally for 1 day, the blood pressure was 150/90, and after the same treatment for 7 days, the blood pressure was lowered to 130/80. 80 was maintained.

Side Effects: None.

Experimental Example 2

Mild hypertension (48 years old, male)

Pretreatment Blood Pressure: 140/100

Method of Treatment: The composition of Example 1 was lowered to 130/90 after administration of 4 tablets per day for 1 day, followed by continued administration in the same manner, and then to 120/80.

Side effects: none

Experimental Example 3

Mild hypertension (60 years old, female)

Pretreatment Blood Pressure: 160/100

Treatment method: After administering the composition of Example 1 once daily for 4 days, the blood pressure dropped to 140/90, and then administered in the same manner, and maintained at 120/80.

Side Effects: None.

Experimental Example 4

Mild hypertension (78 years old, male)

Pretreatment Blood Pressure: 150/100

Treatment method: The blood pressure was 140/90 after oral administration of the composition of Example 1 once a day for 7 days, and the same treatment resulted in 130/80 for 7 days. Maintained.

Side effects: none

Experimental Example 5

Mild hypertension (69 years old, male)

Pretreatment Blood Pressure: 180/90

Method of Treatment: Example 1 was administered 160/80 twice a day, two tablets per day, and then 150/80 dosed in the same manner for two days, and then dropped to 140/80 dosed again for two days, and then continued in the same amount. Maintained at 130/80 administration.

Side effects: none at all.

Experimental Example 6

Mild hypertension (61 years old, female)

Pretreatment Blood Pressure: 190/100

Treatment method: The composition of Example 1 was repeated twice a day for 2 tablets, and after 3 days, it was 160/90, and then after taking 7 tablets daily for 7 days, the blood pressure dropped to 120/80, and then to 1 tablet daily. Normal blood pressure was maintained.

Side effects: none at all.

Experimental Example 7

Mild to severe hypertension (41 years old, female)

Pretreatment Blood Pressure: 160/100

Treatment method: With the composition of Example 8, the blood pressure after 3 days of treatment for 1 tablet per day was 140/90, and in the same manner, the blood pressure after 7 days of further treatment was restored to 130/80.

Side effects: none at all.

Experimental Example 8

Mild hypertension (45 years old, male)

Pretreatment Blood Pressure: 160/100

Treatment method: With the composition of Example 12, the blood pressure after treatment for 1 day 3 tablets was restored to 130/90 normal.

Side effects: none at all.

Experimental Example 9

Mild hypertension (78 years old, female)

Pretreatment Blood Pressure: 140/100

Treatment method: With the composition of Example 13, the blood pressure after 2 days of treatment for 1 tablet per day was restored to 120/80 normal.

Side effects: none at all.

Experimental Example 10

Severe high blood pressure (54 years old, female)

Pretreatment Blood Pressure: 180/110

Treatment method: The composition of Example 1, the blood pressure after treatment for 1 tablet 3 days a day for 140 days, the blood pressure after treatment for 7 days in the same way drops to 130/90, then the blood pressure is 120/80 after 7 days in the same way As normalized.

Side effects: none at all.

Experimental Example 11

Severe high blood pressure (60 years old, female)

Pretreatment Blood Pressure: 200/110

Treatment method: The composition of Example 1 after treatment for 1 day 3 tablets for 1 day was 190/100, then the blood pressure after administration for 6 days twice a day for 6 days was 160/94, again in the same way for 3 days The later blood pressure was 140/90. The blood pressure after 180 days of discontinuation was 180/100. After that, the blood pressure was 140/80 twice a day for 4 days twice daily. After that, blood pressure dropped to 120/8 after 3 days of continuous administration.

Side effects: none at all.

Experimental Example 12

Severe high blood pressure (50 years old, female)

Pretreatment Blood Pressure: 180/110

Treatment method: After administering the composition of Example 1 three days a day, the blood pressure was lowered to 140/100, and once a day after 2 days, the blood pressure was lowered to 120/80 after 3 days.

Side effects: none at all.

Experimental Example 13

Severe hypertension (66 years old, female)

Pretreatment Blood Pressure: 200/110

Treatment method: After administering the composition of Example 1 once daily for 2 days, the blood pressure was 190/100, and in the same manner, the blood pressure after administration for 2 days was 140/90. After that, the blood pressure after administration for 3 days once a day was 160/100, and the blood pressure after administration for 2 days twice a day was 150/90. It then continued down to 130/80 for 4 days in the same manner.

Side effects: none at all.

Experimental Example 14

Severe hypertension (58 years old, male)

Pretreatment Blood Pressure: 160/110

Treatment method: The composition of Example 1 was administered once a tablet two times for four days, 140/90. It was then administered for 7 days in the same manner, 120/80. After that, 1 tablet was continued daily.

Side effects: none at all.

Experimental Example 15

Severe hypertension (44 years old, male)

Pretreatment Blood Pressure: 160/110

Treatment method: The composition of Example 1 was administered once daily for 7 days, 150/100, followed by the same method for 9 days, then dropped to 130/80, and then continued with 1 tablet daily for 120/80. .

Side effects: mild headache but pontal (megenamie acid 150mg cap). 3cap per day. Lost by dosing for 2 days.

Experimental Example 16

Severe hypertension (63 years old, female)

Pretreatment Blood Pressure: 160/110

Treatment method: The composition of Example 1 was administered once daily for 2 days, and became 150/100. Then, the same method was followed for 2 days of administration, then descended to 130/90, and then normalized to 120/80 for 2 days by the same method. being. Then 1/2 tablet once daily, continue normal.

Side effects: none at all.

Experimental Example 17

Severe hypertension (60 years old, male)

Pretreatment Blood Pressure: 160/110

Treatment method: The blood pressure after treatment for 12 days 1 tablet 1 day a day with the composition of Example 1 was restored to normal.

Side Effects: None.

Experimental Example 18

Severe hypertension (68 years old, male)

Pretreatment Blood Pressure: 170/110

Treatment method: The blood pressure of 150/90 after 4 days of administration of the composition of Example 6 to 1 tablet per day, and then to 120/80 after 4 days of the same administration method.

Side Effects: None.

Experimental Example 19

Severe hypertension (43 years old, female)

Pretreatment Blood Pressure: 200/120

Treatment method: The blood pressure after administration of the composition of Example 1 twice daily for 3 days was 180/1 10, and the blood pressure after administration for 3 days was 160/100, and the same method was used for 3 days after administration The blood pressure was 140/90, and in the same way, the blood pressure was restored to 130/80 after 3 days of administration. After that, he continued to take 1 tablet daily, and remained at 120/80.

Side Effects: None.

Experimental Example 20

Severe hypertension (53 years old, male)

Pre-treatment blood pressure: 220/120

Treatment method: The blood pressure after administration of the composition of Example 1 once twice a day for 4 days was 180/110, and the blood pressure after administration for 10 days was 140/90 in the same manner. In the same manner, the blood pressure after the administration for three more days was 130/80, and then 2 tablets daily.

Side Effects: None.

Experimental Example 21

Severe hypertension (62 years old, female)

Pretreatment Blood Pressure: 240/120

Treatment method: The composition of Example 1 was once a tablet twice a day twice a day for two days after administration of blood pressure was 179/110, the same way for another five days after administration 160/110, then administered for 4 days in the same way , 140/100, then administered for 3 days in the same manner, descended to 130/90, and then continued at 120/80 in the same manner.

Side Effects: None.

Experimental Example 22

Severe hypertension (60 years old, female)

Pre-treatment blood pressure: 220/130

Treatment method: Clonidine (* catapress) 1/2 Amp injection and Example 1 the composition is administered twice a day, 1 tablet twice a day, the following day 180/110, then 1 tablet twice daily for 3 days , Descending to 160/100, then administered in the same way for 3 days, 140/90, then continuing in the same way for 3 days, proceeding to 120/80.

Side Effects: None.

Experimental Example 23

Severe hypertension (59 years old, male)

Pretreatment Blood Pressure: 200/130

Treatment method: The composition of Example 1 was administered twice a day for 7 days, 170/120, then 7 days in the same way, 150/98, then 7 days in the same way, 130/90, After 2 days 20 days of 30 days irregularly taking 30 days, blood pressure rises again 200/130, then once a day one tablet for seven days 160 160 drops, then in the same way for 14 days, 130 / It was lowered to 90, and then continued in the same way. What is unusual is that the cholesterol level (cholesterol, trigiyceride) was lowered after 2 months of treatment than before treatment.

Side effects: none at all.

Experimental Example 24

Severe hypertension (63 years old, male)

Pre-treatment blood pressure: 220/130

Treatment method: Catapress 1/2 Amp injection and the composition of Example 1 twice daily 1 day, the next day, blood pressure 180/110, then once 1 tablet twice a day for 50 days, continued to 130/80 The progression and peculiar thing is that the blood lipid level of 50 days before and after treatment was lower than before treatment. Sensitive to mental stress during hospitalization, blood pressure rises frequently, so one tablet is given three times a day, and blood pressure is proceeding to 130/80. Feel refreshed.

Side effects: none at all.

Experimental Example 25

Severe hypertension (62 years old, female)

Pretreatment Blood Pressure: 240/120

Treatment method: The composition of Example 1 was 1 tablet once, twice a day for two days after treatment for two days, blood pressure was 160/110, the same way for five days after administration was 140/110. Continued treatment.

Side effects: none at all.

Experimental Example 26

Severe hypertension (59 years old, male)

Pretreatment Blood Pressure: 160/120

Treatment method: After administering the composition of Example 1 twice daily for 3 days, the blood pressure was 160/110, followed by the same method for 3 days, then the blood pressure was 160/110, again the same way for 3 days, and then the blood pressure was 130 Lowered to / 100, again administered in the same way for 3 days, then the blood pressure was lowered to 120/90, after which the composition of Example 1 was continuously administered once a day.

Side Effects: None.

Experimental Example 27

Severe hypertension (48 years old, female)

Pre-treatment blood pressure: 220/140

Treatment method: Catapress 1/2 Amp injection and the composition of Example 1 twice a day, the next day, blood pressure 180/110, again with catapress 1/2 Amp and twice daily composition 1, 160 / 110, the blood pressure rises without cause the next day 230/140, again the catapress 1 / 2A mp and the composition of Example 1 administered twice a day, the next day to 180/100, then the composition 1 of Example 1 1 tablet twice a day, 160/100 the next day, then again in the same manner, 150/90 the next day, then 130/90 the next day with the same dosage method, then 120/80 with the same dosage method, and then the same Dosing in a way.

Side Effects: None.

Experimental Example 28

Severe hypertension (53 years old, male)

Pretreatment Blood Pressure: 190/130

Treatment method: With the composition of Example 1, the blood pressure after dosing 4 tablets twice daily was 150/90, and after that, the blood pressure after dosing for 8 days was 140/80. Since then, continue to do the same.

Side Effects: None.

Experimental Example 29

Severe hypertension (59 years old, male)

Pretreatment Blood Pressure: 200/130

Treatment method: The composition of Example 1 was 170/1 20 blood pressure after administration twice a day for 1 tablet twice a day, and the blood pressure after administration for 7 more days was 180/120. After that, the blood pressure dropped to 150/98 for 7 days, and continued to be administered.

Side Effects: None.

Experimental Example 30

Severe hypertension (73 years old, female)

Pretreatment Blood Pressure: 180/140

Treatment Method: The composition of Example 1 was 150/100 of blood pressure after administration for 2 days, 1 tablet per day, and the blood pressure after administration for another 4 days was 150/90. I'm continuing treatment after that.

Side Effects: None.

Experimental Example 31

Severe hypertension (63 years old, female)

Pretreatment Blood Pressure: 190/120

Treatment method: The composition of Example 1 was administered twice a day for 3 days once a day, and the blood pressure became 160 / 100. Afterwards, the blood pressure was 160/100 after 3 more doses in the same manner. After that, the blood pressure drops to 140/90, and then dosed for 4 days in the same way. The blood pressure drops to 130/80, and then continues in the same way.

Side Effects: None.

Experimental Example 32

Malignant hypertension (70 years old, female)

Pre-treatment blood pressure: 220/130

Treatment method: After administering the composition of Example 1 twice daily for 3 days, the blood pressure was lowered to 180/110, and then the blood pressure was 160/100 for 4 days in the same manner. In addition, the blood pressure was 140/80 after administration for 3 days in the same manner, and then the blood pressure was rapidly increased to 190/130 without cause during treatment in the same manner. Then, the composition of “Example 2” was administered twice a day, and the blood pressure was 130 Lowered to / 90, blood pressure 170/100 the next morning, dosed in the same way, lowered to 110/80, shortly thereafter 120/80 and then to 150/100. Since the possibility of increasing blood pressure inherent in the future, the composition of Example 2 is continuously administered once a day twice daily.

Side Effects: None.

Experimental Example 33

Severe hypertension (57 years old, female)

Pretreatment Blood Pressure: 260/150

Treatment method: Catapress 1 / 2Amp and 2 ml of prosamide (Lasix), and 1 tablet of the composition of Example 1, blood pressure 200/120 after 3 days, then 1 tablet twice a day, blood pressure 180 / after 3 130, after which captopril 12.5mg was added to one tablet of the composition of Example 1 twice a day, blood pressure 170/120, administered in the same way for 10 days blood pressure 160/120 and then continued in the same way outpatient The blood pressure suddenly increased to 250/200 without any cause, and after admission, catapress 1Ampnifedipine was administered 10mg (1cap), blood pressure lowered to 170/100, and after 2 hours, blood pressure increased to 200/120, the composition of Example 1 soon After taking one tablet, the blood pressure is lowered to 150/80, and then the composition of Example 2 may be raised once a day by taking one tablet twice a day.

Side Effects: None.

As demonstrated by the above theoretical explanations and experimental examples, the composition of the present invention has a timely and accurate effect of reducing blood pressure, and has no side effects. In addition, long-term use is possible because the usage is simple and excellent tolerability. In addition, the composition of the present invention, the earlier the effect of the treatment, the better the effect of the treatment, the worse the effect of the treatment progresses.

This is thought to be due to the development of organic lesions in the peripheral vascular wall later in hypertension. In addition, high blood pressure treatment is more efficient than inpatient treatment. This is caused by mental insecurity due to emotional stress. If you are anxious, you can use 2-10mg of diazepam (Valium), a central nervous system.

Claims (6)

A therapeutic composition for hypertension comprising a β ₁ blocker, an α ₁ blocker, an ACE inhibitor, a diuretic, and a conventional excipient as a sympathetic receptor blocker. Β ₁ blocker as a sympathetic receptor blocker in claim ₁ as β ₁ blocker selected from the group consisting of acebutolol, akenolol, metoprolol, nadolol, propranolol, timolol, phenbutolol, catelol and pindolol, α ₁ blocker Α ₁ blocker selected from the group consisting of prorazine, terrazosin and doxazosin, ACE inhibitors selected from the group consisting of captopril, enarapril, lignonopril and silazapril as ACE inhibitors, droflometiazide as diuretics, Benzthiazide, chlorothiazide, hydrochlorothiazide, hydroflumetiazide, methylclothiazide, polythiazide, trichlormethiazide, crorotalidone, indafamide, metolazone, querettazone, With cyclothiaza, bumetanide, tripamide, proseamide, amylolide, spyronolactone and triamterene Anti-hypertensive agent composition consisting of diuretic agents and conventional excipients selected from the group true luer. The tablet of the hypertension therapeutic modality of claim 1 or 2, wherein the dosage of 1/2 to 1/10 of the amount of each drug is added and mixed with an excipient commonly used in the manufacture of tablets, followed by mixing. A therapeutic composition for hypertension comprising a β ₁ blocker, an α ₁ blocker, an ACE inhibitor, a diuretic and calcium channel blocker, and a conventional excipient. Claim 4 in, as β ₁ blockers is sympathetic receptor blocker Oh detail tolrol, atenolol, benzo program roltol, nadol roll, propranolol, timolol, penpu tolrol, category olrol and pindol pyrrolo β ₁ blocking agent selected from the group consisting of, α a _first blocker Pro piperazine, captopril as an α ₁ blocker, an ACE inhibitor selected from the group consisting of terazosin, and doxazosin, INC la ruffle, the ridge no frills and Silas chair ruffle selected ACE inhibitor from the group consisting of, as a diuretic band fluorenyl methoxy Thiazide, chlorothiazide, hydrochlorothiazide, hydroflumetiazide, methylclothiazide, polythiazide, trichlormethiazide, crorotalidone, indafamide, metolazone, quinetazone, cycl Rotiazide, bumetanide, tripamide, prosamide, amylolide, spironolactone and triamterene As diuretics and calcium channel blockers selected from diltiazem, nicardipine, nifedipine, nitrendipine, and anti-hypertensive agent composition consisting of verapamil. The antihypertensive therapeutic composition in the form of a tablet prepared by adding and mixing excipients commonly used in the manufacture of tablets with a dosage of 1/2 to 1/10 of the amount of each drug according to claim 4 or tablets.