Means for normalizing blood pressure and treatment of hypertension

 

(57) Abstract:

The invention relates to medicine, specifically to medicines, normalizing blood pressure and treatment of hypertension. The invention lies in the fact that the proposed product contains N-carbamoylmethyl-4-phenyl-2-pyrrolidone and pharmaceutically acceptable carriers, and active substances in a single dose contains 0,125-0,500 g, as well as a method for the treatment of hypertension, for the introduction of these tools 20-30 days 1-4 times a day dose of a 0.125 to 1.0. The invention provides a normalization of blood pressure, without causing discomfort, and reduce the frequency of side effects during therapy. 2 S. and 2 C.p. f-crystals, 1 table.

The invention relates to medicine, specifically to lekarstvennym means, normalizing blood pressure and treatment of hypertension.

Hypertension is one of the most serious medical problems. There are many different ways and means of treatment of this disease.

The most common products containing different structure of chemical compounds.

In ropneho actions b) substances affecting water-salt metabolism and reducing the volume of blood plasma, in) substances expanding peripheral vessels. Main neurotropic antihypertensive agents are sympatholytic, b-blockers, and Central stimulants (A2) adrenergic receptors. The neurotropic drugs (Central) actions include: hydrochlorothiazide methyldopa (dopegita), clonidine (clonidine, hamiton, catapresan), guanfacine (astolic), moxonidine (CInt). The use of drugs of this group is limited due to their ability to cause some side effects.

Hydrochlorothiazide methyldopa (encyclopedia of drugs. Moscow. 2000, S. 557) may cause side effects, which are based on autoimmune mechanisms: myocarditis, hemolytic anemia, acute hepatitis, chronic liver damage. In addition, the drug causes side effects that are typical for all blockers acting on the Central nervous system: drowsiness, dry mouth, orthostatic hypotension, galactorrhea, impotence, marked withdrawal syndrome.

Guanfation (astolic) (encyclopedia of drugs. M. 2000, S. 258) refers to drugs, mainly stimulating the Central a-adrenergic receptors. Guanfation more effective than hydrochlorothiazide methyldopa, although pomocnych bradycardia, dizziness, sweating, allergic reactions and very rarely orthostatic effects. It should be administered with caution to patients with atrioventricular block II-III degree, severe cerebrovascular and coronary insufficiency and severe depression. In addition, the drug reduces the reaction rate of the drivers.

The moxonidine (CInt) belongs to a new class of antihypertensive drugs - selektivnym the agonists imidazoline receptors (encyclopedia of drugs. Moscow. 2000, S. 593). Not recommended if you have heart failure, heart rhythm disturbances, angina. Side effects - dry mouth, fatigue and headaches, sometimes dizziness, insomnia and a feeling of weakness in the legs.

Known compound N-carbamoylmethyl-4-phenyl-2-pyrrolidone, he had shown the presence of anti-hypertensive activity in animal experiments (RF Patent 797219, BI 21, 1995) in terms of situational caused by hypertension in animals, which is only an approximate model of human hypertension. Attempts automatic transfer of results obtained on animals, humans and creation on the basis of N-carbamoylmethyl-4-phenyl-2-pyrrolidone dosage forms and spawanie mentioned means include the use of relevant schemes:

Hydrochlorothiazide methyldopa 250 mg 2-3 R/day, every 2 days, the dose is increased to 250 mg, maximum daily dose of 3 g

Guanfation - 1 mg at bedtime, if necessary, increase the dose to 2-3 mg.

The moxonidine - 0.2 mg 1 time a day before or after a meal, to a maximum dose of 0.6 mg per day.

The main disadvantages of these methods is the availability of the used devices side effects and inconvenient regimens.

Closest to the proposed method is a method of treatment involving the use of Clonidine (clonidine) (encyclopedia of drugs. M. 2000, S. 441), which is 2-(2,6-dichlorophenylamino)-imidazoline hydrochloride, according to the following scheme: 0.075 mg 2-4 times a day, then increase the dose to 0.15-0.3 mg treatment from a few weeks up to 6-12 months. He manifests persistent hypotensive effect, but the treatment may be accompanied hypertensive phase. Upon termination of the treatment they are often the syndrome, in addition, has a sedative effect, causing drowsiness, dry mouth. Contraindications - depressive States.

The objective of the invention is to develop an effective means of normalizing blood pressure while minimizing side effects, and p is that will not cause patients a sedative effect and create when receiving unpleasant sensations, and to reduce the frequency of side effects during therapy.

The task is implemented by the proposed tool, comprising as an active ingredient N-carbamoylmethyl-4-phenyl-2-pyrrolidone thanks detected in this connection abilities along with a strong antihypertensive effect to exert a stabilizing effect on blood pressure. To get medicines to N-carbamoylmethyl-4-phenyl-2-pyrrolidone add pharmacologically acceptable excipients and active substances in a single dose contains 0,125-0,500, the Method comprises the application on the basis of N - carbamoylmethyl-4-phenyl-2-pyrrolidone (CFP) at a dose of from 0.125 to 1.0 g 1-4 times per day. Moreover, it is preferable to apply the tool at a dose of 0.75 g of 1 times a day. The course of treatment lasts 20-30 days.

After further research it was found that N-carbamoylmethyl-4-phenyl-2-pyrrolidone in experiments on animals has the ability not only to lower blood pressure, but in some cases, has the ability to normalize blood pressure. By reducing blood pressure in animals was not observed extremely low pokeropie hypertension is a sharp pressure drop at the wrong selection of the dose. The above data allow us to conclude that the non-obviousness of the claimed technical solution, namely the use of N-carbamoylmethyl-4-phenyl-2-pyrrolidone (CFP) in the composition of the medicinal product to normalize blood pressure.

In the study of antihypertensive action of CPP, found that it lowers blood pressure through activation of the Central GABAergic antihypertensive system. It is known that hypertension is linked to many disorders of cerebral and coronary circulation. GABA, its metabolites and substances GABA-positive action can improve cerebral blood circulation, improve functional stability of cerebral blood flow fluctuations in blood pressure, may also have antianginal and coronaridine action. Therefore, the establishment of antihypertensive drugs that reduce blood pressure through activation of the Central GABAergic antihypertensive system, can allow to open new possibilities in the treatment of hypertension.

The proposed tool is a solid drug: tablets or capsules. The method involves the application that is specially selected pharmacologically acceptable excipients and carriers.

The invention is illustrated by the following examples.:

Example 1. Preparation of solid drug.

Powders CFP, lactose, starch sifted through a sieve mesh size of 0.5 mm Sieved powders CFP, lactose prescription number and half of the required amount of starch is poured into a sealed container and thoroughly mixed (for example, on the principle of "drunken barrel"). After this mixture with stirring moistened small portions of pre-cooked 2% aqueous solution of MC-16 (microcrystalline cellulose). The ratio of weight of dry powder and a solution of about 2/1. After adding a solution of MC-16 evenly moistened mass is dried to a brittle condition and collapses on to the screw shredder.

The resulting powder was filled into gelatin capsules of suitable size or tabletirujut. In the latter case, to it add the remaining starch and magnesium stearate (or calcium). The size of the capsules and tablets will be determined dose CFP 0,125-0,500,

The solid composition of the medicinal product, wt.%:

CFP - 45,0-55,0

Starch - 12,0-30,0

MC-16 - 0,3-0,9

Stearate of magnesium (or calcium) - 0.6 to 1.4

Lactose - ptx2">

Study 1.

Comparative study antigipertenzivnoe activity CFP substance and solid dosage forms was carried out in experiments on anesthetized and generalizirovanny cats at a dose of 25-50 mg/kg

Solid dosage form - reduction of blood pressure by 15-20%, with a maximum effect after 60-90 minutes the Effect is almost 4-6 hours, the substance in the same conditions - reduction of 12-17%.

Study 2.

Preventive action CFP studied in animals (rats with genetic hypertension. CPP was administered at a dose of 25 mg/kg of learning roadmap is as follows: 2 weeks - introduction, 2 weeks break, the time of observation 14-15 weeks. In animals of each period was measured twice a GARDEN indirect method using a cuff on the tail artery (on the 2nd and 4th day).

In the control group pressure increased by 34.7%, with the introduction of substance - 12,3%, with the introduction of solid dosage forms to 10.1%.

Studies show that the proposed dosage form is much more effective than substance lowers blood pressure, as well as providing a stronger preventive action.

Example 3

The method of treatment hyperconcentration on eight groups of 12 people in seven groups, taking CPP, and 10 in the placebo group. In the screening period (2 weeks) all candidates for inclusion in the study was a placebo 1 tablet 1 time per day. During treatment patients seven groups took CFP for 4 weeks in seven different schemes. Patients eighth group for 4 weeks placebo. Analyzed the dynamics of blood pressure (BP) at each treatment, and the frequency of the achievements of the antihypertensive effect in groups. In the case of treatment failure within 2 weeks, patients were excluded from the study. Safety was evaluated using a laboratory (biochemical blood analysis, urinalysis) and instrumental (electrocardiography) methods of research and analysis of the diary of the patient.

A comparison of the effectiveness of different schemes apply CFP, the most effective (58.3% of patients) were schemes 0,253 times a day and 0,751 times a day. When the scheme 0,251 once a day antihypertensive CFP was registered in 33.3% of cases, when the schemes 0,1254 times a day, 0,252 times a day, 0,254 times a day and 0.51 times a day pronounced antihypertensive effect was approximately the same and was about 50%. The group is established with representation from the negative effects of the drug on clinical and biochemical parameters, and also on the performance of electrocardiography (ECG). Portability CFP assessed as good, there were no reported serious adverse effect, or adverse effects requiring discontinuation of therapy. The results of the evaluation of individual antihypertensive effect CFP in some groups of patients are shown in table.

The results obtained indicate pronounced antihypertensive effect CFP. The most effective was the scheme 0,253 times and 0,751 times a day, with other schemes, the effect is less pronounced, but they are comparable.

When prescribing antihypertensive drugs for the treatment of patients with stable arterial hypertension currently choose (ceteris paribus) the long-acting drugs, so most predpochtitelney reception mode CFP convenient for the patient and providing a therapeutic concentration of the drug, is of 0.75 or 0.5 to 1 g once a day.

Thus, the proposed tool, normalizing blood pressure, exhibits high efficiency, it allatoxin, availability of more and nootropic activity (Y. G. Bobkov, I. S. Morozov and other Pharmacological characterization of a new Hairdryer is ery promising tool for use in medicine.

The application of this tool in patients revealed no negative effects on clinical and biochemical parameters, portability money was good, not observed sedative action and effect of cancellation, it is convenient to use, since it is possible to use it 1 time per day.

1. Drug to normalize blood pressure, comprising as active ingredient N-carbamoylmethyl-4-phenyl-2-pyrrolidone, characterized in that it additionally contains starch, microcrystalline cellulose, magnesium stearate (or calcium) and lactose in the following ratio, wt.%:

N-Carbamoylmethyl-4-phenyl-2-pyrrolidone - 45,0-55,0

Starch - 12,0-30,0

Microcrystalline cellulose - 0,3-0,9

Stearate of magnesium (or calcium) - 0.6 to 1.4

Lactose - Rest

2. A method of treating hypertension, providing for the introduction into the body of a medicinal product, characterized in that the injected drug under item 1, containing a single dose 0,125-0,500 g N-carbamoylmethyl-4-phenyl-2-pyrrolidone, 1-4 times per day in a dose of a 0.125 to 1.0,

3. The method according to p. 2, characterized in that the medicinal product is administered at a dose of 0.75 g of 1 times a day.

4.

 

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