Agent for correction of abdominal complication in myocardium infarction (variants)

FIELD: medicine, cardiology.

SUBSTANCE: invention proposes an agent for correction of abdominal complications in acute period in myocardium infarction. Proposed agent represents ondansetron or domperidone. Agent reduces frequency of hyperemia occurring, improved indices of intestine contractions, promotes to declining lethality in acute period in myocardium infarction.

EFFECT: improved and valuable medicinal properties of agent.

4 tbl, 6 dwg

 

The proposed group of inventions relates to medicine, namely, pharmacology, and can be used in the treatment of myocardial infarction (mi) for the correction of gastroduodenal complications.

The prototype of the first variant of the present invention is a drug cisapride (Mashkovsky PPM Drugs: a Handbook for physicians, vol. 1, 2001; the performance took place A.A., N. Muradov. Clinical medicine, 1997, No. 7, p.5 3-56), but it is contraindicated in gastric bleeding, and also has a negative impact on the conductance of myocardium.

Known evaluation of the effect of the drug ondansetron on the motility of the stomach and intestines (K. Fukui et al. "Haigan Lang Cancer", 1997, No. 4, s-445).

However, the study of the influence of the drug ondansetron on the state of the motility of the gastrointestinal tract (GIT), the formation and dynamics of acute lethality in THEM was not conducted.

The technical result is an expansion of the means used in the treatment of gastroduodenal complications to THEM.

This technical result is achieved by use of ondansetron as treatment for complications of the gastrointestinal tract.

For the correction of abdominal syndrome acute THEM the drug ondansetron (approved by the Pharmacological Committee of the Russian Federation, registration number 012570/01-2000, 012570/02-2000) was applied on white outbred cover the Ah-males weighing 120-140 g intraperitoneally at a dose of 2 mg/kg of body weight in a volume of 0.2-0.3 ml of 1 times a day for 3 days after the modeling of experimental myocardial infarction by ligation of the anterior descending branch of the left coronary artery by Kogan AH (Simulation of myocardial infarction: a textbook for students, M., MMG, 1979). As control were used rats-males who underwent ligation of the coronary artery and received within 3 days after coronarography once daily intraperitoneally with 0.9% solution of sodium chloride in the same amount.

In animals slaughtered at different stages of the experiment, from the body of the stomach cut out the pieces and were fixed in 10% formalin. Paraffin sections were stained haematoxylin-eosin.

The use of this drug in 50 rats after ligation of the left coronary artery contributed to the reduction of ulcer formation in the gastric mucosa, improve the contractility of the small intestine, reducing mortality in acute myocardial infarction.

Monitoring of indicators characterizing the state of the organs of the gastrointestinal tract in acute myocardial infarction, showed a reduction in the number of injuries to the mucous membrane of the stomach and improve the contractility of the small intestine in rats after coronarography on the background of the drug. Check the tone and amplitude of contractions of the isolated segment of intestine in rats was conducted by the method of Magnus (Nikolaev BTW, the Experimental foundations of pharmacology and toxicology. M., 1941)

The experimental data.

The results histol the strategic research showed the following changes. The thickness of the mucosa in different animals regardless of the length of experience differed considerably. The surface of the mucosa was intact, lined with low cubic epithelium and covered with a small layer of mucus. Fossa of uneven depth, narrow. Patching epithelium smooth, with pale cytoplasm.

The lumen of the glands also narrowed, sometimes almost not detected. The ratio of cellular elements glands did not differ from control and without differences between groups. It should be noted uneven plethora in vessels of different type and caliber. A significant plethora of surface vessels departments own plates mucosal and submucosal basics, starting with 3 days of observation and up to 9 days, was pronounced and some animals differed from the control. Often plethora combined with stasis, there was a small hemorrhage. In the deeper sections of the mucosa, the submucosa was determined reasonable uneven lymphoma, eosinophilic infiltration. In the later stages of the experiment, the wall of the stomach did not differ from the control.

Study of the influence of the drug ondansetron in the organs of the gastrointestinal tract of male rats after myocardial infarction showed that the use of the drug reduces the number of ulcers in the stomach and AROS is th, and also reduces the frequency of occurrence of hyperemia (Table 1).

Visual inspection of the intestine showed that all rats of the control group had a decrease in tone in comparison with intact animals, while in the experimental group, these changes were observed only in half of the animals.

Figure 1-3 shows the parameters of contractility of the isolated segment of the small intestine in acute myocardial infarction on the background of the application of ondansetron. Modeling of myocardial infarction causes a reduction of the initial tone of the isolated segment of intestine in rats (figure 1) as compared with intact animals already on the third day, and an even greater reduction in tone (more than 2-fold) after 7 days after coronarography. The use of the drug ondansetron in 3 days after myocardial infarction was slightly lowered the tone of the intestine by 31% from the control. Willingness to barium spasm (figure 2) after 3 days after modeling THEM increased almost 3 times, and after 7 days after coronarography increased by 4 mm, the Use of ondansetron for 3 days after coronarography reduced this figure is slightly below the norm (the norm adopted indicators obtained from intact animals. The study of intestinal contractility in response to karbaholina (figure 3)showed that after 3 and 7 days after modeling THEM carbacholine spasm HC is growing about 2 times. The use of ondansetron does not affect carbacholine spasm, reinforced on the background of THEM.

The influence of the drug ondansetron in mortality of animals after coronarography: in the control group, the death of animals after ligation of the left coronary artery was observed in the acute period - killed 40% of the animals, whereas in the experimental group during the acute lethality was not. According to the data obtained in animals after simulation of experimental myocardial infarction in the background of the application NT, the antagonist ondansetron has decreased damage of the gastric mucosa, reducing the willingness to barium and carbacholine spasm, reducing mortality in acute myocardial infarction. Thus, the use of ondansetron in outbred rats-males after coronarography contributed to the reduction of the manifestations of gastrointestinal complications in acute myocardial infarction.

The prototype of the second variant of the invention is the preparation bromopride (Mashkovsky PPM Drugs: a Handbook for physicians, vol. 1, 2001), but it does not antiulcer action.

Known evaluation of the effect of the drug domperidone on the motility of the stomach and intestines (Loginov A.S., Y. Vasiliev Practitioner, 1997, No. 10, p.28; Babak OA nursing, 2000, No. 2, pp.62-66).

However, the study of the influence of the drug domperidone at state Moto is IKI digestive tract, the ulceration and mortality in the dynamics of acute myocardial infarction was not conducted.

The technical result is an expansion of the means used in the treatment of gastroduodenal complications of myocardial infarction. This technical result is achieved by the use of domperidone as a drug for treatment of complications from organs gastrointestinal tract.

For the correction of abdominal syndrome acute myocardial infarction drug domperidone (approved by the Pharmacological Committee of the Russian Federation, registration number 011655/01 - 2000) was applied on white outbred rats male weighing 120-140 g intraperitoneally at a dose of 2 mg/kg of body weight in a volume of 0.2-0.3 ml of 1 times a day for 7 days after the modeling of experimental myocardial infarction by ligation of the anterior descending branch of the left coronary artery by Kogan AH (Simulation of myocardial infarction: a textbook for students. M, MMI, 1979). As control were used rats-males who underwent ligation of the coronary artery and received within 7 days then once daily intraperitoneally with 0.9% solution of sodium chloride in the same amount. In animals slaughtered at different stages of the experiment, from the body of the stomach cut out the pieces and were fixed in 10% formalin. Paraffin sections were stained haematoxylin-eosin.

Note the persistence of this drug in 50 rats after ligation of the left coronary artery contributed to the reduction of ulcer formation in the gastric mucosa, improve the contractility of the small intestine, reducing mortality in acute myocardial infarction.

Monitoring of indicators characterizing the state of the organs of the gastrointestinal tract in acute myocardial infarction, showed a reduction in the number of injuries to the mucous membrane of the stomach and improve the contractility of the small intestine in rats after coronarography on the background of the drug. Check the tone and amplitude of contractions of the isolated segment of intestine in rats was conducted by the method of Magnus (Nikolaev BTW, the Experimental foundations of pharmacology and toxicology. M., 1941)

The experimental data.

The histological examination showed the following changes. The thickness of the mucosa in different animals regardless of the length of experience differed considerably. The surface of the mucosa was intact, lined with low cubic epithelium and covered with a small layer of mucus. Fossa of uneven depth, narrow. Patching epithelium smooth, with pale cytoplasm. The lumen of the glands also narrowed, sometimes almost not detected. The ratio of cellular elements glands did not differ from control and without differences between groups. It should be noted uneven plethora in vessels of different type and caliber. A significant plethora of surface vessels departments who own plate mucosal and submucosal basis, starting with 3 days of observation and up to 9 days, was pronounced and some animals differed from the control. Often plethora combined with stasis, there was a small hemorrhage. In the deeper sections of the mucosa, the submucosa was determined reasonable uneven lymphoma, eosinophilic infiltration. In the later stages of the experiment, the wall of the stomach did not differ from the control.

Study of the influence of the drug domperidone on the organs of the gastrointestinal tract of male rats after myocardial infarction showed that the use of the drug reduces the number of ulcers in the stomach and erosion, and reduces the frequency of occurrence of hyperemia. (Table 1).

The influence of the drug domperidone on mortality of animals after coronarography: in the control group, the death of animals after ligation of the left coronary artery was observed in the acute period - killed 40% of the animals, whereas in the experimental group during the acute lethality was not.

Visual inspection of the intestine showed that all rats of the control group had a decrease in tone in comparison with intact animals, while in the experimental group, these changes were observed only in half of the animals.

Figs.4-6 presents the parameters of contractility of the isolated segment of small intestine during myocardial infarction is the application of domperidone. Modeling of myocardial infarction causes a reduction of the initial tone of the isolated segment of intestine in rats compared with intact animals already on the third day, and an even greater reduction in tone (more than 2-fold) after 7 days after coronarography (figure 4). The use of the drug domperidone within 3 days after myocardial infarction significantly increases the tone of the intestine to levels comparable with the control, and within 7 days after the modeling of experimental myocardial infarction increased the initial tone is somewhat stronger. Willingness to barium spasm (figure 5) after 3 days after modeling THEM increased almost 3 times, and after 7 days after coronarography increased by 4 mm, the Use of domperidone for 3 days after coronarography somewhat reduced this figure, and within 7 days had reduced this figure to below normal by 2 mm Study of intestinal contractility in response to karbaholina (6) showed that after 3 and 7 days after modeling THEM carbacholine spasm increases approximately in 2 times. The use of domperidone in 3 days reduces carbacholine spasm to normal, and within 7 reduces carbacholine spasm in 2 times below normal. (Table 4).

According to the data obtained in animals after simulation of experimental myocardial infarction in the background of the application BL is Katara D2-receptors domperidone has decreased damage of the gastric mucosa, the decline in readiness for barium and carbacholine spasm, reducing mortality in acute myocardial infarction. Thus, the use of domperidone in outbred rats-males after coronarography contributed to the reduction of the manifestations of gastrointestinal complications in acute myocardial infarction.

Means for the correction of abdominal complications of myocardial infarction.

Table 1
The effect of ondansetron on the condition of the gastric mucosa after 3 and 7 days after coronarography
animalsDamage to the mucosa of the stomach, %
hyperemiaerosionulcers
the intact---
On the background of the 3-day MI1007050
On the background of the 3-day for THEM and the introduction of ondansetron903039
On the background of a 7-day MI100 73100
On the background of the 7 days of administration of ondansetron first 3 days362440
Table 2
The effect of ondansetron on indicators of change in the contractility of the isolated segment of the small intestine in the dynamics of myocardial infarction
animalsMetric mm
The initial toneBarium spasmCarbacholine spasm
the intact3,9±0,89a 9.5±1,0819,8±1,37
On the background of the 3-day MI2,29±0,2625,5±2,638,5±2,14
On the background of the 3-day for THEM and the introduction of ondansetron2,0±0,246,5±0,9934,75±2,81
On the background of a 7-day MI1,6±0,2729,5±2,732,3±to 3.73
On the background of the 7 days of administration of ondansetron first is E. 3 days 1,9±0,396,3±0,4235,7±4,88

Table 3
Effect of domperidone on the condition of the gastric mucosa after 3 and 7 days after coronarography
animalsDamage to the mucosa of the stomach, %
hyperemiaerosionulcers
the intact---
On the background of the 3-day MI1007050
On the background of the 3-day for THEM and the introduction of domperidone711342
On the background of a 7-day MI10073100
On the background of a 7-day THEM and the introduction of domperidone30the 17.350
Table 4
The effect is of domperidone on indicators of change in the contractility of the isolated segment of the small intestine in the dynamics of myocardial infarction
animalsMetric mm
The initial toneBarium spasmCarbacholine spasm
the intact3,9±0,89a 9.5±1,0819,8±1,37
On the background of the 3-day MI2,29±0,2625,5±2,638,5±2,14
On the background of the 3-day for THEM and the introduction of domperidone3,7±0,7719,5±1,2320,8±2,09
On the background of a 7-day MI1,6±0,2729,5±2,732,3±to 3.73

The use of ondansetron or domperidone as a means for correction of abdominal complications during the acute period of myocardial infarction.



 

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SUBSTANCE: invention relates to derivatives of benzimidazole of general formulae (IV)

and

For compounds of the formula (IV): R represents hydrogen atom, (C1-C10)-alkyl and others; D represents phenyl or azaphenyl; n = 0; A, B and Q represent hydrogen atom, (C1-C10)-alkyl and others; Z represents a bond, (C1-C6)-alkylene or -CH2O-; R1 represents hydrogen atom, (C1-C10)-alkyl and others; R2 represents hydrogen atom. For compounds of the formula (IVA): n = 0; Z represents a bond, -CH2-, -CH2O-, -CH2CH2-; R represents hydrogen atom or (C1-C10)-alkyl; R1 represents hydrogen atom, (C3-C12)-cycloalkyl, benzyl and others; R2 represents hydrogen atom. Compounds of formulae (IV) and (IVA) possess affinity with respect to nociceptin and μ-receptors and can be used in medicine.

EFFECT: valuable medicinal properties of compounds.

18 cl, 5 tbl, 16 ex

FIELD: medicine, dermatology.

SUBSTANCE: the present innovation deals with treating different forms of localized sclerodermia: plaque, linear, scleroatrophic lichen, idiopathic atrophodermia. The method deals with introducing delagyl, xanthinol nicotinate, claritine, application of "Elocom" ointment. At the background mentioned one should alternate 8-10 procedures of intravenous injection of ozonized physiological solution at ozone concentration being 1.5 mg/l at the volume of 200 ml and 5-7 procedures of subcutaneous puncturing in lesion foci with oxygen-ozone gaseous mixture at ozone concentration of 2 mg/l. This mixture should be introduced along focal periphery at the volume of 10-30 ml. Intravenous injections should be carried out twice or thrice weekly, and subcutaneous puncturing - once or twice weekly. The innovation enables to decrease sickness rate due to increased velocity and full-value absorption of the ointment used, immunomodulating, antiphlogistic, collagen-formation and microcirculation normalizing effect of complex therapy, liquidation of tissue hypoxia and reflexogenic stimulation of body vascular system.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new piperidine compounds of the general formula (I) wherein A means preferably ring of the formula:

wherein R1 means hydrogen atom (H), cyano-group (CN), (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkenyl, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group; W means (C1-C6)-alkylene that can be substituted, ordinary bond; Z means optionally substituted aromatic hydrocarbon cyclic (C6-C14)-group; l means a number from 0 to 6. Compounds show the excellent activity directed for inhibition of sodium channels and selective inhibition of potassium channels.

EFFECT: improved preparing method, improved inhibiting method, valuable medicinal properties of compounds.

26 cl, 4 tbl, 476 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new azaheterocycles comprising fragment of piperidin-2-yl- of the general formula (1):

as separate enantiomers or mixture of enantiomers, or their pharmaceutically acceptable salts, oxides or hydrates. In compounds of the formula (1) R1 represents hydrogen atom, inert substitute or NH-protecting substitute; W represents optionally substituted azaheterocycle, such as: pyridin-3-yl, pyrazolo[1,5-a]pyridin-6-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-7-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-9-yl, imidazo[1,2-a]pyrimidin-6-yl, imidazo[1,2-a]pyrimidin-8-yl or [1,8]naphthyridin-3-yl. Compounds elicit activity with respect to nicotine receptors and can be used in pharmaceutical industry. Also, invention relates to the focused library for search of physiologically active compound-leaders, and to pharmaceutical compositions based on new compounds of the formula (1).

EFFECT: valuable medicinal and pharmacological properties of compounds.

9 cl, 1 tbl, 15 sch, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of cyclic amide of the formula (I)

or its salt, or hydrate, or solvate wherein X represents (C1-C6)-alkyl, (C1-C6)-alkyl substituted with phenyl, (C2-C6)-alkenyl substituted with phenyl or halogenphenyl, (C2-C6)-alkynyl substituted with phenyl, phenyl that can be substituted with (C1-C6)-alkyl; one or more halogen atom, nitro-group, phenyl, (C1-C6)-alkoxy-group, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy-group, phenyl-(C1-C6)-alkyl, (C1-C6)-alkoxyphenyl-(C1-C6)-alkyl, amino-group, optionally substituted with (C1-C6)-alkyl, acetyl, (C1-C6)-alkoxy-group, substituted with phenyl, phenylcarbonyl, furanyl; 1- or 2-naphthyl, monocyclic (C3-C8)-cycloalkyl, amino-group substituted with one or more substitutes taken among phenyl, halogenphenyl, (C1-C6)-alkoxyphenyl, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl, phenyl-(C1-C6)-alkyl; 5- or 6-membered monocyclic heterocyclic group comprising 1 or 2 heteroatoms, such as nitrogen (N), oxygen (O), sulfur (S) atom optionally substituted with halogenphenyl, halogen atom, benzyl, (C1-C6)-alkyl, phenyl; 8-10-membered bicyclic heteroaryl group comprising 1 or 2 heteroatoms taken among N, O and optionally substituted with halogen atom; 8-10-membered polycyclic cycloalkyl group; Q means -CH2-, -CO-, -O-, -S-, -CH(OR7)- or -C(=NR8)- wherein R7 means hydrogen atom (H), (C1-C6)-alkyl; R8 means OH, (C1-C)-alkoxy-group, acylamino-group, (C1-C6)-alkoxycarbonylamino-group, phenyl-(C1-C6)-alkoxy-group; n = 0-5; B represents group or wherein each among R3, R4, R5 and R6 represents independently substitute taken among group consisting of hydrogen atom (H), halogen atom, NO2 (nitro-group), (C1-C6)-alkoxy-group, CN (cyano-group); m = 1 or 2; ring represents 5- or 6-membered aromatic heterocyclic ring comprising one or two heteroatoms taken among O, S, N. Compound of the formula (I) elicit activity inhibiting binding sigma-receptors that allows their using as component of medicinal agent.

EFFECT: valuable medicinal properties of compounds.

21 cl, 2 sch, 4 tbl, 183 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention proposes a pharmaceutical preparation based on angiotensin-converting enzyme inhibitor, its using in prophylaxis of insult, diabetes and/or congestive cardiac insufficiency and corresponding methods for its using in patient with maintenance heart function and subjected for risk of cardiovascular attack due to previous history of ischemic disease, insult or peripheral arterial disease. In particular, inhibitor of angiotensin-converting enzyme can be chosen from ramipril, ramiprilat, lisinopril, enalapril and enalaprilat. Invention promotes to reducing the total lethality of patients group in case of cardiovascular diseases, cardiac attacks and insults, the necessity for carrying out procedures for revascularization (such as surgery operation for coronary shunt, angioplasty with using balloon and so on) and diabetic complication are diminished.

EFFECT: improved and valuable medicinal properties of preparations.

19 cl, 1 ex

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