RU2268714C1 - Agent with hypolipidemic activity - Google Patents

Abstract

FIELD: medicine, in particular agent with hypolipidemic activity.

SUBSTANCE: claimed agent represents N-isopropylamide-2-(2-phenylethyl)aminoethanesulfoacid chlorohydrate which is known drug for ulcer treatment. Agent of present invention provides lowered cholesterol and triglyceride levels in serum, liver and aorta and blocks lipolysis.

EFFECT: new agent for dislipoproteinemia correction useful in treatment and prophylaxis of arteriosclerosis.

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Description

The invention relates to the expansion of the arsenal of lipid-lowering drugs that affect blood cholesterol and triglycerides in the treatment of cardiovascular diseases associated with metabolic disorders, such as hyperlipidemia and atherosclerosis, by using N-isopropylamide-2- (1-phenylethyl) hydrochloride for this purpose aminoethanesulfonic acids.

Previously, this drug has been described as a means for the treatment of gastric ulcer and duodenal ulcer [RF Patent No. 2179439, BI No. 5 of 02/20/2002]. A pharmacological analysis showed that N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride affects the cholesterol and triglycerides in the blood and liver, and therefore can be used as a lipid-lowering agent.

Hyperlipidemia means conditions in which the blood contains an increased content of lipoproteins - carriers of cholesterol (cholesterol) and triglycerides (TG). According to generally accepted notions, an increase in the content of these lipoproteins contributes to the development of atherosclerosis.

Currently, lipid-lowering drug therapy is recognized as the main way to reduce the development of atherosclerosis and its complications.

In human blood, lipids are in complex with specific proteins - in the form of lipoproteins (LP), of which two classes: very low density lipoproteins (VLDL) and low density lipoproteins (LDL) are highly atherogenic. Relatively non-atherogenic - chylomicrons, performing a transport function, transferring triglycerides of food origin from the intestinal wall. High density lipoproteins (HDL) are non-atherogenic, exhibiting anti-atherosclerotic effect against the vascular wall.

Hypolipidemic agents are necessary for diseases such as diabetes mellitus, hypothyroidism, acute myocardial infarction, angina pectoris, arterial hypertension, during organ transplantation and coronary artery bypass grafting. In these cases, atherogenic dyslipoproteinemia (DLP) develops, which aggravates the course of the disease and the postoperative period, and in diabetes mellitus it is one of the causes of high mortality from complications of atherosclerosis.

Clofibrate is known for the treatment of hyperlipidemia, causing a decrease in the content of cholesterol and TG in the blood, TG in very low density lipoproteins (VLDL) and cholesterol in low density lipoproteins (LDL). However, when using the drug, intrahepatic cholestasis can develop, gallstone disease, hepatomegaly become aggravated [J.Atherosclerosis, 1983, 49: 255-266].

Another drug, Gemfibrozil, reduces VLDL in the blood of patients with hypertriglyceridemia who do not respond to treatment with other lipid-lowering drugs. In addition, it increases the concentration of high density anti-atherogenic lipoproteins (HDL). With the use of gemfibrozil, gastrointestinal upsets, anemia, and leukopenia are possible. In this regard, individual selection of lipid-lowering drugs in the treatment of dyslipoproteinemia and atherosclerosis is required.

The relevance of the search for new lipid-lowering drugs is that these drugs should regulate the ratio between atherogenic and non-atherogenic lipoproteins, eliminate metabolic disorders in the arterial wall, thus exerting an anti-atherosclerotic effect.

N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride exhibits lipid-lowering activity in various hyperlipidemic models and has low toxicity.

The pharmacological analysis showed that N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride affects the cholesterol and triglyceride levels in the blood and is a lipid-lowering agent.

Preclinical trials of the drug allow recommending it as a lipid-lowering agent in the treatment of hyperlipidemia and cardiovascular diseases.

The preclinical study of the lipid-lowering effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride was carried out in accordance with the requirements of the Pharmaceutical Committee of the Ministry of Health of the Russian Federation [Guidance on the experimental preclinical study of new pharmacological substances (edited by V.P. Fisenko), 2000. P.224 -227].

The essence of this invention is that N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride effectively reduces cholesterol and triglyceride levels, as well as atherogenic lipoproteins in models of hyperlipidemia in different animal species. The drug increases the level of anti-atherogenic lipoproteins and prevents the development of experimental atherosclerosis. According to the severity of the lipid-lowering effect, N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride is not inferior to clofibrate and approaches gemfibrozil in its activity.

The drug is highly effective both for parenteral and oral administration, is devoid of central action and side effects, can be used as a lipid-lowering agent or in combination with traditional therapy for the prevention and treatment of atherosclerosis.

The drug has no analogues in Russia and abroad.

The hypolipidemic activity of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride was studied under experimental hyperlipidemia in rats and guinea pigs. Based on the results of biochemical studies of the aorta, liver, and blood serum, the hypolipidemic activity of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride was judged.

Determination of cholesterol (cholesterol) in blood serum. The level of cholesterol in the blood serum of rats and guinea pigs was determined by the colorimetric enzymatic method (CHOD-PAP) using a kit of reagents from Vital Diagnostics.

Determination of cholesterol, high density lipoproteins or α-cholesterol (α-cholesterol) in blood serum. The study of the content of α-cholesterol in rat blood serum was carried out as described above using reagents from Vital Diagnostics at a wavelength of 546 nm on SF-26 after preliminary deposition of low density lipoproteins (LDL) with heparin in the presence of Mn ions [Lab. Case 1979, No. 1: 36-41].

Determination of triglycerides (TG) in serum. The determination of TG in the blood serum of rats and guinea pigs was carried out using a Vital Diagnostics reagent kit photometrically [In: Methods of Enzymatic Analysis Acad. Press, N.Y. 1974: P.1831].

The cholesterol (cholesterol) in the liver of rats and guinea pigs was determined colorimetrically using the Lieberman-Burchard reaction after extraction of a liver sample with chloroform-methanol mixture [In: Lipids and Steroid Hormones in Clinical Medicine. Ph. 1960: 6-10].

Determination of triglycerides (TG) in the liver. The content of TG in the liver of rats and guinea pigs was determined by the method of Nary and Frings [Clin. Chem. 1973, v.19, No. 10: p. 1201-1202].

The content of total cholesterol in the aorta of rats and guinea pigs was determined colorimetrically using the Lieberman-Burchard reaction after extraction of a portion of the aorta with a chloroform-methanol mixture.

Determination of the level of non-esterified fatty acids (NEFA) in rat serum. NEFA was determined in a blood serum sample after extraction with chloroform using a color reaction with diethyldithiocarbamate [J. Lipid Res. 1965, v.6, No. 1: 16-20].

The experimental results were statistically processed using Student's t-test.

The effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the level of serum lipids in rat triton hyperlipidemia model

Hyperlipidemia in rats was induced by administration of the newt detergent WR-1339 (225 mg / kg, once, intraperitoneally, Serva, Switzerland). This model is characterized by the development of powerful, persistent hyperlipidemia in male rats weighing 250-300 g [Lipids 1972, v.7, No. 1: 68-74]. In this case, an increase in the level of cholesterol is 5-6 times, and TG 10-20 times compared with the content of these indicators in normolipidemic animals. N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride was administered to rats intraperitoneally at a dose of 25 mg / kg twice (before and with the introduction of newt). The degree of hyperlipidemia was assessed by the level of lipids: cholesterol and triglyceride in blood serum of rats. Clofibrate (Hinoin, Hungary) was administered intraperitoneally at a dose of 100 mg / kg as a comparison drug.

In the group of animals with hyperlipidemia caused by triton, a significant increase in the content of cholesterol and triglyceride in the blood serum was observed (table 1).

Under the influence of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride, a significant decrease in cholesterol (cholesterol) and triglycerides (TG) levels was noted by 36% and 41%, respectively, compared with the group of animals with hyperlipidemia. Intraperitoneal administration of clofibrate at a dose of 100 mg / kg caused a decrease in the content of cholesterol and TG by 59% and 42%, respectively (table 1).

Table 1
Effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the development of experimental hyperlipidemia in rats caused by intraperitoneal administration of the newt detergent WR-1339 Indicators
Groups of animals Serum Lipids (mmol / L) Total cholesterol Triglycerides 1. Intact rats
n = 12 1.29 ± 0.14 0.54 ± 0.09 2. Triton WR-1339 225 mg / kg, iv, once
n = 12 6.51 ± 0.32 9.36 ± 0.82 P _2-1 <0.001 <0.001 3. N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride 25 mg / kg, br / triton WR-1339
n = 12 4.16 ± 0.47 5.57 ± 0.16 P _3-2 <0.001 <0.001 4. Clofibrate 100 mg / kg / br + Triton WR-1339
n = 12 3.20 ± 0.14 5.42 ± 0.54 P _4-2 <0.001 <0.001

Thus, the hypolipidemic effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride is comparable to clofibrate, but its effective dose is 4 times lower than clofibrate.

The effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the development of experimental hypertriglyceridemia in rats caused by the introduction of ethanol for 3 days

In rats weighing 220-250 g, the model of alcoholic hypertriglyceridemia was reproduced by the modified Wojcicki method [J. Arzneimittel - Forsch 1976, v. 26, No. 11: 2047-2048]. Male rats were three times orally given a 50% ethanol solution at a dose of 6 g / kg, which caused them to increase the content of TG in the blood serum and in the liver. N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride was preliminarily administered orally for five days at a dose of 50 mg / kg, the last administration 30 minutes before the introduction of ethanol. As a comparison drug used gemfibrozil firm "Lechiva" (Czech Republic) at a dose of 50 mg / kg

Studies have shown that in rats with hypertriglyceridemia caused by a three-day administration of ethanol, there is a 3-fold increase in the level of TG in blood serum and a 4.5-fold increase in the liver compared to intact animals (table 2).

table 2
The effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the development of experimental hypertriglyceridemia in rats caused by the introduction of ethanol for 3 days Indicators Triglycerides Groups of animals Blood serum (mmol / l) liver (mg / g crude tissue) 1. Intact male rats
n = 12 0.58 ± 0.03 3.1 ± 0.25 2. 50% solution of ethanol 6 g / kg 3 days
n = 12 1.86 ± 0.23 14.1 ± 1.2 P _2-1 <0.001 <0.001 3. N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride 50 mg / kg orally + 50% ethanol solution
n = 12 1.33 ± 0.11 10.8 ± 0.83 P _3-2 <0.05 <0.05 4. Gemfibrozil 50 mg / kg orally + 50% ethanol solution
n = 12 0.95 ± 0.13 10.7 ± 0.65 P _4-2 <0.01 <0.05

The introduction of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride caused a significant decrease in the concentration of TG in serum by 29%, and in the liver by 24%. The comparison drug gemfibrozil reduced serum TG levels by 49% and in the liver by 29%.

Thus, in the model of alcoholic hypertriglyceridemia, N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride had a pronounced hypotriglyceridemic effect, comparable with the effect of gemfibrozil.

The effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the level of unesterified fatty acids (NEFA), triglycerides (TG) under rat lipolysis

It is known that lipolysis and lipogenesis in adipose tissue play an important role in lipid metabolism. Determining the concentration of unesterified fatty acids (NEFA) in serum reflects the intensity of lipolysis in adipose tissue. Inhibition of lipolysis is essential in the mechanism of some known lipid-lowering drugs.

The model of adrenaline-stimulated lipolysis was reproduced in experiments on male rats weighing 220-240 g. To stimulate lipolysis in adipose tissue, animals were injected with adrenaline intraperitoneally, once at a dose of 1.5 mg / kg. 30 minutes after the injection of adrenaline, serum levels of NEFA and TG were determined. N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride was administered intraperitoneally for five days at a dose of 25 mg / kg; the last time - 1 hour before the start of the experiment or 30 minutes before stimulation with adrenaline. As a reference drug, nicotinic acid was used at a dose of 250 mg / kg ip.

Under the conditions of adrenaline-induced lipolysis, in the blood serum of rats of the experimental group there was a 2.5-fold increase in the concentration of NEFA and 2-fold the content of TG (table 3).

Table 3
The effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the level of non-esterified fatty acids (triglyceride NEG) under rat lipolysis Indicators Serum Lipids (mmol / L) Groups of animals NEZHK TG 1. Intact rats
n = 12 213.3 ± 28.6 0.58 ± 0.07 2. N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride 25 mg / kg iv 5 days (1 hour after the last injection)
n = 12 456.6 ± 43.2 0.66 ± 0.08 P _2-1 <0.001 3. Niacin 250 mg / kg iv 5 days (1 hour after the last injection)
n = 12 262.7 ± 80.5 0.93 ± 0.07 P _3-2 <0.01 4. Adrenaline 1.5 mg / kg ip, once (taking blood after 30 minutes)
n = 12 549.0 ± 32.8 1.00 ± 0.06 P _4-1 <0.001 <0.001 5. N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride 25 mg / kg ip 5 days (30 minutes after the last administration of adrenaline 1.5 mg / kg ip, once, taking blood after 30 min)
n = 12 448.7 ± 29.1 0.59 ± 0.04 R _5-4 <0.05 <0.01 6. Niacin 250 mg / kg ip 5 days (30 minutes after the last administration of adrenaline 1.5 mg / kg ip, once, blood sampling after 30 min)
n = 12 406.7 ± 19.8 0.57 ± 0.10 P _6-4 <0.01 <0.01

Administration of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride at a dose of 25 mg / kg for 5 days reduced the level of NEFA increased by adrenaline 1.2 times and TG 2 times. An analogy picture was observed when using the well-known hypolipolytic drug nicotinic acid, which was administered at a dose of 250 mg / kg for 5 days (table 3).

Thus, in its lipolytic and hypolipidemic effect, N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride is comparable to nicotinic acid, but its effective dose is 10 times lower than that of the nicotinic acid comparison drug.

The effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the development of experimental dyslipoproteinemia in rats caused by an atherogenic diet

The lipid and lipoprotein blood spectra of experimental animals of different species are significantly different: in guinea pigs, almost all cholesterol is contained in atherogenic drugs (LDL and VLDL), in rats, many cholesterol is found in the antiatherogenic fraction of LP - HDL. In this regard, rats are more resistant to the induction of experimental hyperlipidemia [J. Exp. Med. 1959, v. 109, No. 3: 293-309].

The experiments were carried out on male rats weighing 230-250 g in experimental dyslipoproteinemia (DLP), which is characterized by an increased content of lipids and LP of serum and liver and a reduced content of high density α-ChL LP (HDL). These disorders were caused by a modified diet containing 7.5% cholesterol, 500,000 units of vitamin D ₂ and a 30% mixture of animal fats and warmed sunflower oil [Chem. Pharm. J. 1999, No. 11: 14-16]. The duration of this special diet was 21 days. The peculiarity of this diet is that against its background it is possible to study not only the lipid-lowering effects of the new compounds, but also to show the possibility of their influence on the level of cholesterol of the antiatherogenic fraction of LP - HDL, and judging by the content of total cholesterol in the aorta about their potential antiatherosclerotic effect.

N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride was administered orally at a dose of 50 mg / kg. Clofibrate at a dose of 100 mg / kg and gemfibrozil at a dose of 50 mg / kg of body weight of experimental rats were used as comparison preparations. The levels of total cholesterol, TG, and α-cholesterol were determined in the blood serum of animals. In the liver, the content of cholesterol and TG was determined, in the aorta, the content of total cholesterol.

The research results showed that in the group of animals that received an atherogenic diet for 21 days, there was a significant increase in the serum and liver lipids in comparison with intact rats (table 4).

Table 4
The effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the development of experimental dyslipoproteinemia in rats caused by an atherogenic diet for 21 days Indicators Serum Lipids (mmol / L) Liver lipids (mg / g crude tissue) Aorta (mg / g crude tissue) Groups of animals XC α-XC TG XC TG XC 1. Intact rats 1.29 0.64 0.53 3.40 4.1 1.65 n = 10 ± 0.06 ± 0.04 ± 0.06 ± 0.24 ± 0.35 ± 0.44 2. Atherogenic diet 21 days 3.86 0.37 1,67 11.6 197 4.68 ± 0.39 ± 0.01 ± 0.06 ± 0.67 ± 1.7 ± 0.52 n = 10 P _2-1 <0.001 <0.001 <0.001 0.001 0.001 0.001 3 N-Isoprochloride Hydrochloride pilamide-2- (1-phenylethyl) aminoethanesulfonic acid 50 mg / kg orally + diet, 21 days 2,36 0.50 1,04 2.71 8.69 3.09 ± 0.16 ± 0.05 ± 0.11 ± 0.7 ± 0.28 ± 0.23 n = 10 P _3-2 0.001 <0.05 <0.01 0.001 0.001 0.05 4. Gemfibrozil 50 mg / kg oral + diet, 21 days 2.70 0.62 1.23 2.79 7.56 2.09 ± 0.16 ± 0.07 ± 0.09 ± 0.39 ± 0.64 ± 0.23 n = 10 P _4-2 <0.05 <0.01 0.05 0.001 0.001 0.02 5. Clofibrate 100 mg / kg oral + diet, 21 days 2.91 0.45 1.15 5.25 12.0 3.8 ± 0.27 ± 0.02 ± 0.04 ± 0.72 ± 1.0 ± 0.42 n = 10 R _5-2 <0.05 0.01 0.001 0.01

The use of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride at a dose of 50 mg / kg reduced the level of total cholesterol, triglycerides in blood serum by 1.6 times in comparison with animals that received only an atherogenic diet. Under the influence of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride in animal blood serum, an increase in the level of α-cholesterol in anti-atherogenic drugs and a significant decrease in lipids in the liver of cholesterol was observed by 4.3 times, and TG by 2.3 times. According to its hypolipidemic activity, N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride is comparable to the action of clofibrate, but its effective dose is 2 times lower than that of clofibrate (table 4).

Under the influence of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride, the increased content of cholesterol in the rat aorta of the experimental group caused by an atherogenic diet decreased 1.5 times. This protective effect against aortic lipoidosis was also observed in the gemfibrozil comparison drug.

Thus, N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride caused a pronounced hypolipidemic effect in experimental animals resistant to the creation of dyslipoproteinemia and aortic lipoidosis.

The effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the development of experimental dyslipoproteinemia in guinea pigs induced by an atherogenic diet for 16 days

This animal species is highly sensitive to the induction of hyperlipidemia due to the low concentration of antiatherogenic HDL in the blood serum. The alimentary DLP model was reproduced on male guinea pigs weighing 450-500 g, induced by introducing through the tube into the stomach 2 ml of a mixture containing cholesterol in a dose of 0.5 g / kg along with fats and heated vegetable oil for 16 days. N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride was administered through a tube into the stomach at a dose of 50 mg / kg. Comparison preparations were administered orally: clofibrate at a dose of 100 mg / kg, gemfibrozil at a dose of 50 mg / kg.

The research results showed that the cholesterol serum cholesterol content of guinea pigs receiving an atherogenic diet increased by 6.6 times, TG by 7 times, liver lipid infiltration increased by 7 times, and the level of total cholesterol in the aorta increased by 6 times compared with intact animals (table 5).

Table 5
The effect of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride on the development of experimental hyperlipidemia in guinea pigs induced by an atherogenic diet for 16 days Indicators Serum Lipids (mmol / L) Liver lipids (mg / g crude tissue) Aortic lipids (mg / g crude tissue) Groups of animals XC TG XC TG XC 1. Intact Guinea Pigs
n = 8 1.23 ± 0.10 0.44 ± 0.05 4.2 ± 0.3 5.3 ± 0.5 3.10 ± 0.64 2 Diet (cholesterol + fat mixture) 16 days
n = 8 8.15 ± 0.62 3.10 ± 0.18 30.2 ± 2.7 35.1 ± 3.6 19.06 ± 0.87 P _2-1 <0.001 <0.001 <0.001 <0.001 <0.001 3. N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride 50 mg / kg orally + diet, 16 days
n = 8 5.99 ± 0.37 1.96 ± 0.10 19.2 ± 3.4 23.1 ± 2.6 15.42 ± 0.36 P _3-2 0.01 <0.001 <0.05 <0.01 <0.01 4. Gemfibrozil 50 mg / kg orally + diet, 16 days
n = 8 4.73 ± 0.35 1.72 ± 0.13 17.8 ± 2.2 21.3 ± 4.5 12.03 ± 0.27 P _4-2 <0.001 <0.001 <0.01 <0.01 <0.001 5. Clofibrate 100 mg / kg orally + diet 16 days
n = 8 7.02 ± 0.58 2.0 ± 0.09 25.1 ± 3.4 24.0 ± 1.3 17.6 ± 1.25 R _5-2 <0.01 <0.01

In the group of guinea pigs treated with N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride at a dose of 50 mg / kg on a diet, a significant decrease in serum cholesterol and triglyceride levels was shown by 27% and 37%. In the liver, the lipid content decreased by 1.5 times.

Administration of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride significantly inhibited aortic lipoidosis in experimental guinea pigs (Table 5). At the same time, in guinea pigs receiving clofibrate at a dose of 100 mg / kg, only a hypotriglyceridemic effect was observed with respect to blood serum and liver, and no hypocholesterolemic effect was detected in the aorta.

Thus, studies conducted on experimental dyslipoproteinemia in guinea pigs showed that the hydrochloride of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid in terms of the effectiveness of the lipid-lowering effect approaches gemfibrozil and exceeds clofibrate in a number of indicators by 1.2-1.4 times.

In a series of experiments on rats with stimulated administration of adrenaline by lipolysis, the property of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride was found to reduce the level of unesterified fatty acids of blood serum and block lipolysis.

N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride has a pronounced lipid-lowering effect. It has the ability to increase low cholesterol of high density anti-atherogenic lipoproteins.

The low toxicity of N-isopropylamide-2- (1-phenylethyl) aminoethanesulfonic acid hydrochloride and its effectiveness when used in a small dose indicate the potential of this substance as a means of preventing and treating atherosclerosis, since it substantially corrects the main factor of the development of the latter - atherogenic dyslipoproteinemia.

Claims (1)

The use of N-isopropylamide-2- (1-phenylethyl) amino-ethanesulfonic acid hydrochloride as a lipid-lowering agent.