Zaporizhzhia State Medical University Research Articles (Page 5)

The aim of the study. To investigate the effect of thiotriazolin on oxidative stress and bone metabolism in patients with a combined course of type 2 diabetes and osteoporosis, who permanently reside in industrial region.Materials and methods. On the basis of the educational and scientific medical center University Hospital of Zaporizhzhia State Medical University, 44 patients with combined course of type 2 diabetes and osteoporosis, who permanently resided in Zaporizhzhia, were examined for the period from 2016–2017. 22 patients received standard basic therapy for type 2 diabetes and osteoporosis, and 22 patients additionally received thiotriazolin. Patient groups were comparable in age, sex, and duration of type 2 diabetes mellitus. All patients studied the concentration of markers of oxidative stress (nitrotyrosine, 8-hydroxyguanine) and bone metabolism (osteocalcin and deoxypyridinoline).Results. Patients with a combined course of type 2 diabetes mellitus and osteoporosis who received basic therapy with thiotriazolin supplementation registered a significant decrease in the concentration of oxidative stress. Thus, in patients of the second group, there was a significant decrease in the serum level of nitrotyrosine by 5.5 times (pl0.05) and 8-hydroxyguanine by 2.1 times (pl0.05). When evaluating markers of bone metabolism in patients of the second group, the level of osteocalcin increased by 24 % (pl0.05), and the concentration of deoxypyridinoline significantly decreased in individuals of both groups, but in the group with the addition of thiotriazolin, its rate decreased by 30%, and in the first group only 16 % (pl0.05).Conclusions. In patients with a combined course of type 2 diabetes and osteoporosis, which, in addition to basic therapy, thiotriazolin was included, a significant decrease in markers of oxidative stress was registered in a daily dose of 600 mg for 3 months. Under the influence of basic therapy with the addition of thiotrazoline, a significant increase in bone formation and a decrease in bone resorption were observed in patients with a combined course of type 2 diabetes and osteoporosis

It is known that both chronic obstructive pulmonary disease and arterial hypertension are multifactorial diseases, and develop as a result of a complex interaction of genetic and environmental factors. The purpose of this work was to study the metabolism of caspase-7 and caspase-9 in patients with chronic obstructive pulmonary disease (COPD) in combination with arterial hypertension (AH). Materials and methods. We examined 23 patients with a diagnosis of essential hypertension stage II and COPD stage II without a clinically significant concomitant pathology. The plasma level of caspase-7 and caspase-9 was determined using the appropriate ELISA test systems (manufacturer – Bender Medsystems, Austria) at the Medical and Laboratory Training Centre of Zaporizhzhia State Medical University in accordance with the instructions attached to the kit. The analysis of the dynamics of the studied cysteine ​​proteases indicates a statistically significant elevation of these apoptosis markers in the conditions of hypertension and COPD. The value of caspase-7 in the cohort of patients with COPD + AH significantly exceeded similar figures for the groups of patients with a single pathology presented by AH or COPD, and averaged 0.41 ± 0.09 ng / ml. A statistically significant elevation of the caspase-9 level in patients with COPD + AH up to 2.16 ± 0.29 ng / ml compared with other groups also indicates a more significant induction of apoptotic processes in comorbid pathology than in isolated AH or COPD. Conclusion. The obtained results require further clarification of the nature of the relationship between changes in the metabolism of cysteine ​​proteases and the primacy of pathogenetic processes in the mechanisms of risk formation for complications and progression of ventilation disorders in patients with COPD and comorbid essential hypertension.

During last years clopidogrel keeps leading positions among medicines with platelet antiaggregation mechanism. The rectal dosage form with clopidogrel, namely suppository containing 0.075 g of active substance on hydrophilic base with addition of 2 % twin-80 was proposed by the Department of Medicinal Preparations Technology (Zaporizhzhia State Medical University on the base of complex investigations. The aim of present work is the study of structural-mechanical characteristics of rectal dosage form with clopidogrel depending on the temperature of technological process of supposirory manufacturing. The study of structural-mechanical characteristics of suppository mass with clopidogrel was carried out using the rotational viscosimeter “Rheotest2”with cylinder device at the human body temperature (37 oС) and at temperature of manufacturing technological process. Results . Results testify presence of structure in suppository mass system, because limit shear stress increases and effective viscosity decreases with deformation speed rising. Conclusions . Study of consistent characteristics of suppository mass with clopidogrel on polyethylenoxyde base with addition of 2 % twin-80 at the human body temperature was carried out. It was established that it is structural system with expressed thixotropic properties and with the uniform distribution of active substance and excipients both at the moment of manufacturing and during administration or long storage. It was revealed that increasing of temperature of suppository mass to 50 oС doesn't lead to essential modification of its structural-mechanical characteristics and transformation into Newtonian system. Taking obtained results into account it was determined that temperature rate of manufacturing of rectal suppositories with clopidogrel on the hydrofiflic base (processes of mixing, homogenization, pouring into forms) within 50–55 oС creates sufficient fluidity of mass for unhampered technological process and thixotropy of suppository mass providing the uniform distribution of active substance and excipients in this dosage form.

Мета роботи – аналіз проведення іспиту як основної форми контролю в сучасній системі вищої освіти з точки зору його ефективності; дослідження позитивних сторін та недоліків даної форми рубіжного контролю; аналіз шляхів поновлення іспиту, його нових форм та можливість їх використання в практиці викладання в медичному ВНЗ.
 Основна частина. У статті представлені різноманітні форми контролю знань, що застосовуються у Запорізькому державному медичному університеті: вхідний (попередній, діагностичний), поточний (здійснюється безперервно, відстежує рівень знань, умінь і навичок студентів на практичних заняттях), рубіжний (контроль знань, умінь і навичок після закінчення модуля або курсу), відстрочений та підсумковий. Підсумковий контроль ­ державна атестація ­ проводиться у вигляді державних іспитів, у тому числі захисту випускної кваліфікаційної роботи.
 Висновки. Основною формою диференційованого рубіжного контролю в ВНЗ є іспит. Іспитом закінчується вивчення предмета або його основного розділу, причому викладач не може відмовитися від даної форми контролю хоча б тому, що вона вказана в навчальному плані, обов’язковому документі, якого необхідно дотримуватись.

Purposeful synthesis of derivatives of 1,2,4-triazole is one of the most important branches of modern pharmaceutical science
 Modern pharmaceutical market of domestic medicines requires constant updates of existing range. It makes possible the synthesis of new compounds with a predicted biological activity.
 The main advantage of derivatives of 1,2,4-triazole is high efficiency and low toxic. That is promising factor for creation of new chemical compounds.
 Analysis of literary data of past few years has showed that there is not enough information about synthesis, physical, chemical and biological properties of derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol in the literature.
 So synthesis and further research of derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol is topical.
 The research took place at the Department of toxicological and inorganic Chemistry of Zaporizhzhia State Medical University (the head of the department – professor O. I. Panasenko).
 During the work the research were the physicochemical properties of newly synthesized of compounds in accordance with the methods described in the State Pharmacopoeia of Ukraine.
 As starting substance was used 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol obtained by cyclization of of potassium 2-atsetilgidrazinkarboditioata in the medium hydrazine hydrate.
 It is planned to research of the compounds obtained in the antimicrobial, act-protective, antioxidative and hypolipidemic activity.
 9 new compounds of ylidene derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol were synthesized in a research. The structure of the new synthesized of substances was confirmed by with by means of modern of instrumental methods analysis (1H-PMR-spectroscopy, chromato-mass-spectrometry, elemental analysis). The obtained data is possible to use in purposeful synthesis for the further research of biologically active compounds.

Acne dermatosis (rosacea, perioral dermatitis, seborrheic dermatitis etc.) are one of the most actual problem in dermatology. Praziquantel is an antiparasitic medication effective towards trematodes, cestodes. Investigations developed by domestic scientists revealed antidemodicosis activity of praziquantel. Use of semisolid dosage forms for rectal administration will allow to increase its efficacy and minimize the risks of adverse reactions.
 On the department of technology of medications Zaporizhzhia State Medical University research of development of praziquantel rectal dosage form for therapy of acne dermatosis, complicated with demodicosis, and its technology is carried out. As a result of biopharmaceutical investigations it was determined that combination of excipients – the base (confectionary fat 60%, 10% paraffin, 30% cocoa butter) and surfactant (distilled monoglycerides) provides with the optimal praziquantel releasing.
 The aim of this work is study of excipient using in manufacturing of suppository (bases and surfactants) influence on the biopharmaceutical characteristics of praziquantel rectal dosage form.
 Investigation was carried out by the one-factors dispersive analysis with repeated observations By way of a parameter of optimization praziquantel releasing was chosen as the first step of bioavailability investigation. Praziquantel releasing from suppository was studied by the equilibrium dialysis by Kruvchinsky’s method at temperature 37 ± 0,5 °С through a cellophane semipermeable membrane «Kuprofan» film using Franz diffusion cell apparatus. Ethyl alcohol was chosen as a dialysis medium considering the solubility of praziquantel. Concentration of released praziquantel after 30 minutes of the dialysis was determined by spectrophotometric analysis.
 As a result of biopharmaceutical investigation of praziquantel suppositories it was determined that surface-active substances (distilled monoglycerides) concentration has a statistically significant influence on its releasing from rectal dosage form. It was ascertained that 0,5% concentration of distilled monoglycerides provides with the optimal releasing of praziquantel from rectal suppositories.

Diuretic drugs are drugs that, by blocking the transport systems of the renal tubules, promote the removal of excess electrolytes and water from the body, normalization of the internal environment. They eliminate edema, reduce the fluid content in the body cavity. Diuretic drugs differ in their chemical structure, the mechanism of on the urinary tract function of the kidneys and on the mechanisms of regulation of this function. It should be noted that the use of the above mentioned agents can lead to undesirable side effects, such as nausea, vomiting, unpleasant sensations in the stomach, headache, facial hyperemia. To date, there is evidence that 5-R-1,2,4-triazole derivatives have diuretic activity. The advantage of synthetic triazole derivatives is that, along with the expressed pharmacological of the compound, there are relatively low rates of acute and chronic toxicity, but almost no side effects. Therefore, it is important to create new low-toxic substances of derivatives (3-thio-4-R-4- H -1,2,4-triazole-3-yl)(phenyl)methanols and study their diuretic properties. The purpose of the work is the purposeful search for new low-toxic and highly effective diuretic compounds among the derivatives of (3-thio-4-R-4- H -1,2,4-triazole-5-yl)(phenyl)methanols. Materials and methods. To establish the influence of compounds, which have been synthesized at the Physical and Chemical Chemistry Department of ZSMU, the method of E. B. Berchin was used on the excretory function of kidneys. Experiments on diuretic were conducted at the Department of Clinical Pharmacy, Pharmacotherapy and MFE of FPE, Zaporizhzhia State Medical University. Results. The diuretic of derivatives (3-thio-4-R-4 H -1,2,4-triazole-5-yl)(phenyl)methanols was investigated. The study and analysis of the obtained experimental data were compared with the reference diuretic hypothiazide. Regularities structure – activity were established. The studies indicate that (3-thio-4-R-4H-1,2,4-triazoles-3-yl)(phenyl)methanol are not able to exceed hypothiazide diuretic effect, but 4-(5-hydroxy(phenyl)methyl-4-phenyl-4 H -1,2,4-triazolе-3-ylthiomethyl)benzonitrile showed the results closer to the reference drug. Conclusion. By the method of E.B. Berchin the diuretic of derivatives (3-thio-4-R-4 H -1,2,4-triazol-5-yl)(phenyl)methanols was investigated. Derivatives (3-thio-4-R-4H-1,2,4-triazole-3-yl)(phenyl)methanols do not excee the diuretic of hypothiazide. Patterns structure – action were established. The most active compound was 4-(5-hydroxy(phenyl)methyl-4-phenyl-4 H -1,2,4-triazolе-3-ylthiomethyl)benzonitrile.

Clinicians pay close attention to the questions related to the diagnosis and treatment tactics of stomach defects with its obstruction in view of their stable frequency and lack of consensus on these diseases development mechanisms. The insufficient individual experience of every clinician leads to the difficulties in early diagnostic and the most adequate surgical intervention choice, and so, high rates of mortality. Purpose of the work. Improvement of the diagnostic and treatment tactic in infants with gastric duplication. Materials and methods. Clinical experience of two cases of the newborn children treatment with rare variants of digestive tract developmental defects is presented. In one child it was a case of stomach cystic duplication; and the other had a cystic duplication of stomach and duodenum. Results. There have been 5 cases of the stomach duplication treatment in the last 5 years in the Pediatric Surgery Clinic of Zaporizhzhia State Medical University. Two children were diagnosed with this pathology in neonatal period. Clinical analysis of these cases is described in the article. Both infants have undergone the early operative intervention. Type and extent of the operation depended on the peculiarities of localization, sizes, clinical signs of the defects and the general state of patients. The main stages and methods of medical-diagnostic process of such patients’ management are presented. Conclusions. The analysis shows that the efficacy of stomach obstruction rare forms diagnosis is achieved by usage of algorithms based on the staged modern diagnostic methods, taking into account their resolution and congenital anomaly type. In congenital stomach and duodenum duplication maximal informativness can be achieved using ultrasound and CT (or MRI) of the abdominal cavity. The most effective and non-invasive is ultrasound method by high-resolution devices. The discussed clinical cases are examples of early diagnosis of the stomach duplication and the right choice of active tactics for such children management that has made it possible to obtain a successful treatment outcome.

Respiratory epithelial clearance timely and early disorder diagnosis in patients suffering from chemo-resistant pulmonary tuberculosis (CRPTB) concomitant pathology of the bronchial mucosa is an actual problem of modern phthisiology, the solution of which will allow the timely application of rational correction, which will increase the effectiveness of this category treatment among patients.Objective is to investigate the nature and features of respiratory epithelial clearance disorders among patients suffering from CRPTB with comorbidity of the bronchi mucous membrane by using the developed method of these disorders diagnosis.Materials and methods. The respiratory epithelial clearance state diagnosis was carried out among 133 patients with CRPTB at the beginning of the intensive phase of antimycobacterial therapy during fibrobronchoscopy, provided there is a concomitant specific pathology of the mucous membrane (including its combination with non-specific endobronchitis). Average age of patients was 36.5 ± 1.1 years old. There were 89 (66.9 %) men and 44 (33.1 %) women. The tracheobronchial tree diagnostic fibrobronchoscopy with further study of the respiratory epithelial clearance condition among patients suffering from CRPTB was carried out by V. M. Khlystun at Phthisiology and Pulmonology Department of Zaporizhzhia State Medical University in CI “Zaporizhzhia Regional Antituberculous Clinical Dispensary”. Criteria of patients including into the research: existence of resistance of tuberculosis mycobacteria to anti-mycobacterial drugs in patients with new and repeated cases of tuberculosis, existence of pathology of the mucosa of bronchi confirmed during fiberoptic bronchoscopy. Serious associated diseases (HIV infection/AIDS, diabetes mellitus, etc.) were criteria of exception. The condition of bronchial mucosa was studied under narcotic anaesthesia by fiberoptic bronchoscopes of Olympus (Japan). Pathology of a bronchial tree was described according to classification by M. V. Shesterina, A. N. Kalyuk (1975). Results of the research are processed by modern methods of the analysis using the personal computer with the statistical package Statistica® for Windows 6.0 license program (StatSoft Inc., No. AXXR712 D833214FAN5).Results. There were respiratory epithelial clearance disturbances in 94.7 %, which predominate with the 1st and 2nd stages of mucociliary inefficiency (51.1 % and 37.6 %). There was mucociliary inefficiency dependence on the bronchi mucous membrane pathology nature: the incidence of respiratory epithelial clearance in patients with concomitant bronchial tuberculosis in combination with the nonspecific purulent endobronchitis is 2.4 times higher than in those with concomitant bronchial tuberculosis only (70.7 % vs 29.3 %). The association of nonspecific purulent endobronchitis with concomitant bronchial tuberculosis leads to an increase in the mucociliary inefficiency degree of severity, due to its diffuse localization, where it is diagnosed more often than in the limited one, thus, mucociliary inefficiency of the 2nd stage of severity (64.9 % vs 24.6 %, is 2.6 times more (64.9 % vs 24.6 %) and 4.6 times more in the 3rd stage (16.2 % vs 3.5 %).Conclusions. The proposed method for the diagnosis of mucociliary inefficiency disorders among patients suffering from CRPTB with bronchial mucosa concomitant pathology allows to diagnose mucociliary inefficiency and mucociliary inefficiency dependence on the bronchi mucous membrane pathology nature.

Досвід організації допомоги студентам з первинною артеріальною гіпертензією у Запорізькому державному медичному університеті

Objective: The aim of the work was to determine the validation characteristics for the developed method of quantitation of 1-(β-phenylethyl)-4- amino-1,2,4-triazole bromide substance by absorption spectrophotometry in the ultraviolet region (UV).Methods: For study purposes, the 1-(β-phenylethyl)-4-amino-1,2,4-triazole bromide substance and the standard sample, obtained by the state enterprise “plant of chemical reagents” of scientific and technological complex “institute of single crystals” of the National Academy of Sciences of Ukraine, was used. In the course of our work, we used chemical, physical, physicochemical (absorption spectrophotometry in the UV region), and statistical methods of analysis. The study was carried out at the Laboratory for Standardization and Technology of Medicines at the Department of Pharmaceutical Chemistry at Zaporizhzhia State Medical University (Ukraine).Results: In the previous studies, we have developed a technique for spectrophotometric determination of the quantitative content of 1-(β-phenylethyl)- 4-amino-1,2,4-triazole bromide substance. The results of the studies showed that the absorption curve in the UV region of the substance solution has three absorption maxima, namely: λ1=252 nm, λ2=258 nm, and λ3=263 nm. To quantify the substance, the wavelength λ2=258 nm was used. The results of the quantitation of the 1-(β-phenylethyl)-4-amino-1,2,4-triazole bromide substance by spectrophotometric method prove that the technique developed by us is accurate and reproducible and meets the current requirements. To the developed methodology to ensure accurate and accurate analysis results, its validation was carried out. According to the requirements of the State Pharmacopoeia of Ukraine (2 editions), the developed method for quantitation of the substance was checked for such validation characteristics as specificity, linearity, range of application, accuracy, correctness, and robustness.Conclusions: As a result of the work, it was proved that the method of quantitation of 1-(β-phenylethyl)-4-amino-1,2,4-triazolе bromide substance by spectrophotometric method is valid.

The article presents the experience of educational site creation on platform of Facebook social network for interns and postgraduates of family medicine, therapy and cardiology department of Zaporizhzhia State Medical University. It describes the principles of educational pages functioning, main forms and training options. It presents the possibilities of interactivity based on the social network Facebook. The discussion includes the advantages and disadvantages, as well as options to improve this form of distance education.

Мета роботи – провести комплексний аналіз інформації щодо забезпечення студентів усіх спеціальностей вищих навчальних закладів МОЗ України підручниками, навчальними посібниками, довідковою та іншою навчальною літературою та оцінити відповідність вимогам щодо провадження освітньої діяльності у сфері вищої освіти.Основна частина. Комплексний аналіз інформації щодо забезпечення студентів вищих навчальних закладів МОЗ України навчальною літературою, що здійснюється Державною установою «Центральний методичний кабінет з вищої медичної освіти МОЗ України», свідчить про те, що у 2016/2017 навчальному році загальні показники забезпеченості навчальною літературою студентів ВНЗ МОЗ України в цілому суттєво не зросли. При цьому виявлено найгірші показники щодо забезпеченості у 2016/2017 навчальному році навчальними книгами студентів спеціальності «Технологія фармацевтичних препаратів» та «Клінічна фармація». Найвищі показники забезпеченості підручниками у 2016/2017 навчальному році студентів спеціальностей «Лікувальна справа», «Педіатрія», «Медико-профілактична справа» зафіксовано у Харківському національному медичному університеті; ДВНЗ «Тернопільський державний медичний університет імені І.Я. Горбачевського МОЗ України» та Запорізькому державному медичному університеті. Виявлені особливості забезпечення студентів вищих навчальних закладів МОЗ України навчальною літературою дозволяють оцінити відповідність вимогам щодо провадження освітньої діяльності у сфері вищої освіти та надати рекомендації.Висновок. Для реалізації забезпечення навчальною книгою здобувачів вищої освіти у вищих навчальних закладах МОЗ України, що є необхідною умовою виконання навчальним закладом Ліцензійних умов провадження освітньої діяльності, необхідно створити умови для активізації профільних фахівців вищих навчальних закладів щодо написання сучасної навчально-методичної літератури, виділяти достатню кількість коштів на придбання та видання медичних книг.

CHOICE OF RATIONAL EXCIPIENTS TO CREATE "HYPERTRIL" TABLETS BY DIRECT PRESSING Report 1. “Investigation of the effect of excipients on the technological characteristics of the hypertril's powder masses” N.V. Parnyuk, L.I. Kucherenko, O. O. Portna Zaporozhye State Medical University, Zaporozhye Key words: hypertril, excipients, powders masses, direct pressing Introduction Cardiovascular diseases are the most common cause of death in the Ukraine and in the world, but in the Ukrainian society awareness of the risk factors is very low, and mortality - is very high. Arterial hypertension (AH) is the most common among the pathologies of the cardiovascular system. Staff members of SPA "Farmatron" (Zaporizhzhia) in collaboration with the Department of Pharmaceutical Chemistry of Zaporizhzhia State Medical University synthesized new original compound bromide 1- (β- phenylethyl)-4-amino-1,2,4-triazole and got the certificate of trademark called "Hypertril". During pharmacological studies, we revealed that hypertril has combined properties of cardioselective s 1 - adrenoceptor blocking agent and peripheral vasodilator, thus showing antihypertensive, antiischemic and antioxidant properties. Systematic preclinical studies of hypertril as antihypertensive drug made it possible to establish ED (effective dose) of 50 to animal and predict the advisability of its taking to human in dose of 20 mg per reception. In the course of studying the literature sources we came to the conclusion that drugs for the treatment of hypertension are used for a long time. Most drugs for the treatment of cardiovascular diseases are used in tablet form. Based on the foregoing, it is urgent to develop technology of tablets based on "Hypertril" containing 20 mg of active ingredient. Thus, the aim of our work is the development of technology of "Hypertril" tablets with 20 mg of active ingredient. Materials and Methods The studies of rational choice of excipients to create "Hypertril" tablets by direct pressing were undertaked. We studied six excipients groups having different physical and technological properties. We studied 30 excipients, most of which appeared on the market in recent years and have no examples in pharmaceutical technology for tablet drugs creating. One tablet contained 0.02g of hypertril, 0.082 g samples of MCC (microcrystalline cellulose) (factor A), 0.040g of sugar sample (factor B), 0.010g of disintegrant (factor C), 0.040g of crystalline substances (factor D), 0,006g of glidants (factor E) and 0.002g lubricants (factor F). In the study of six qualitative factors we used one of the plans of analysis of variance – six-factor experiment based on Hyper-Greco-Latin square. Based on this carried out analysis we concluded the impact of studied factors on pharmaco-technological properties of the hypertril powder masses. Research results The results of analysis of variance showed that all six studied factors as follows: D> A> C> F> E> B affect hypertril’s free bulk of powder blend; after shrinkage - A> D> C> E > B> F affect hypertril’s tapped bulk density, also all the factors affect flow powder blend: D> E> B> A> C> F, angle of natural repose of hypertril’s powders - D> C> E> A> B> F. In the study of powder masses on indicants of free bulk of powder blend, tapped bulk density, fluidity and angle of natural repose, we found that in most series of experiments powder masses have technological properties that indicate the possibility of tablets’ creating by direct pressing. The studies have shown that studied six groups of excipients manifest "leaders" in effect on one or another pharmaco-technological powder masses index. Conclusions The effect of six excipients groups on technological characteristics of hypertril’s powder masses is studied. In most series of experiments, powder masses have technological properties that indicate the possibility of tablets’ creating by direct pressing.

<p align="center"><strong>ON THE STANDARDIZATION OF HYPERTRIL SUBSTANCE</strong></p><p align="center">Kucherenko L.I.</p><p align="center">Zaporozhye State Medical University</p><p align="center">SPC «Pharmatron»</p><p><em>Key words:</em> substance, Hypertril, standardization, identification, nonaqueous titration</p><p><strong>Introduction.</strong> Increase of mortality and disability caused by cardiovascular diseases is the problem not only of health protection institutions, it is the social problem of our society. Efficiency of health care service in Ukraine depends on the presence of highly effective competitive drugs of domestic production. Especially it concerns drugs used for treating of cardiovascular diseases, notably coronary heart disease, arterial hypertension, myocardial infarction and acute heart failure. So the development of drugs for treatment of mentioned diseases is the urgent task of modern medicine and pharmacy. According to the recommendations of The European Society of Cardiology important components of complex therapy of heart failure especially after myocardial infarction are the following drugs: β-adrenoceptor antagonists, ACE inhibitors and diuretics. Thus primary task of pharmacy and medicine is the developing and improvement of new highly effective and safe drugs using of which would lead to the improvement of quality of life and its extension. All about mentioned urge to develop perfectly new antianginal and antihypertensive remedy of original structure which has minimum side effects.</p><p>At the Pharmaceutical Chemistry Department of Zaporizhzhia State Medical University in collaboration with the SPC "Pharmatron" new original compound – derivative of 4-amino-1,2,4-triazole (drug Hypertril) was synthesized.</p><p><strong>Objective. </strong>The aim of this investigation is the development of Hypertril substance standardization methods.</p><p><strong>Methods.</strong> On the basis of structural formula of Hypertril and methods of its receiving we have worked out the draft of quality control methods (QCM) for the substance. While developing it we used latest modern methods of standardization which are ordered by State Pharmacopoeia of Ukraine (SPU) and the European Pharmacopoeia.<em></em></p><p><strong>Results and discussion. </strong>For identification of Hypertril substance we proposed to carry out characteristic reaction (C) for bromide ion notably with the solution of chloramine in the presence of dilute hydrochloric acid and chloroform (chloroform layer receives yellow-brown colour). Besides, taking into account modern standardization methods we proposed to determine correspondence of infrared spectrum of the substance with the infrared spectrum of pharmacopeia standard sample.<em></em></p><p>Next task was the development of methods of quantitation of Hypertril substance. First we studied the possibility of Hypertril substance titration with 0.1M solution of perchloric acid with the use of internal indicator and determination of point of equivalence potentiometrically. As solvent we used acetic acid nonaqueous. The investigation showed that the substance is soluble in acetic acid nonaqueous only under prolonged heating. Results received were satisfactory and were from 98.5% up to 101%. But taking into consideration the time one analysis takes we believe this method is not to be practical. To reduce the Hypertril substance analysis duration we proposed to dissolve weighed portion preliminarily in formic acid nonaqueous and then add acetic acid nonaqueous. During the analysis of Hypertril substance according to this method we received unsatisfactory results in the limits from 94% up to 98%. In further investigations we used as solvent the mixture of formic acid nonaqueous with acetic anhydride. As indicator we used crystal violet and defined point of equivalence potentiometrically. While using internal indicator there were some difficulties because the transition of coloring was not clear. Thus we proposed to define point of equivalence potentiometrically. During analysis we received satisfactory results and analysis duration shortened three times.</p><p><strong>Conclusions.</strong> According to the results of the investigations we can conclude that developed method of defining of quantitative content of Hypertril substance by nonaqueous titration is easy-to-use and simple, accurate, reproducible and corresponds to all demands of State Pharmacopoeia and international standards. Further worked out methods of qualitative and quantitative determination of Hypertril substance are planned to introduce into QCM for Hypertril substance.</p>

<p align="center">L.I.Kucherenko, N.V.Parnyuk, Z.B.Moryak</p><p><strong>DEVELOPMENT </strong><strong>OF QUANTITATIVE DETERMINATION METODS </strong><strong>FOR THE STEPWISE CONTROL OF "HYPERTRIL" TABLETS PRODUCTION</strong><strong></strong></p><p align="center">Zaporizhzhia State Medical University</p><p align="center">“Pharmatron” Scientific-and-Production Corporation</p><p><strong><em>Key words</em></strong>: <em>hypertril, tablet mass, tablets, spectrophotometry</em><strong> </strong></p><p><strong>Introduction</strong></p><p>Last 20-25 years inUkraineare characterized by unfavorable demographic situation, a significant increase in morbidity and mortality. The deterioration ofUkrainepopulation health is often caused by cardiovascular diseases. Therefore, the development of treatments for diseases of the cardiovascular system is the actual problem of modern medicine and pharmacy. This led to the creation of fundamentally new antianginal and antihypertensive medication of original structure, which will have a minimum of side effects. At the Department of Pharmaceutical Chemistry of Zaporizhzhia State Medical University in collaboration with the SPC "Pharmatron" under the direction of Professor Mazur I.A, a new original compound - bromide 1-β-phenylethyl-4-amino-1,2,4-triazole (hypertril) is received and shows antihypertensive, antiischemic and antioxidant properties. Most drugs for the treatment of cardiovascular disease are used in pill form. Therefore, the new elected rational drug dosage form is a pill.</p><p><strong>The aim of research </strong></p><p>Development of methods of standardization, in particular quantitative content of hypertril in tablet weight by physical and chemical methods.</p><p><strong>Materials and methods </strong></p><p>During technological research a drug (pill average weight0.15 grams) containing0.02 gof active substance, was developed. During the stepwise control of pill's production the greatest attention is paid to quality control of tablet weight. One of the most modern methods of pharmaceutical analysis is instrumental methods, including spectral one.</p><p><strong>Results and discussion </strong></p><p>During previous studies, we have developed a method of spectrophotometric determination of hypertril substance. The studies showed that the absorption curves in the UV region of our and standard designs are identical and absorption maxima coincide. For the qualitative and quantitative determination of hypertril in tablet weight, a spectrophotometric determination method was approbated. Also it was developed and used to standardize hypertril substance.</p><p><em>Identification of the substance in hypertril tablet weight by spectrophotometry. </em></p><p>We measure the optical spissitude of the prepared solution of hypertril tablet weight.</p><p><em>Preparation of standard solution (comparison solution). </em>We measure the optical spissitude of the standard sample at a wavelength λ = 258 nm. As a standard substance we use hypertril sample (state owned enterprise "Plant of chemical reagent" of Science and Technology Complex "<em>Institute for Single Crystals</em> " NAS of Ukraine), which meets the requirements of quality control methods. Terms of spectrophotometric determination.</p><p>Optical spissitude measurement of solutions was held by scanning spectrophotometer Optizen POP, relatively solvent water, the thickness of the cuvette -1 cm, wavelength λ = 258 nm. As a result of our research the methodology of standardization of hypertril in tablet weight was designed by spectrophotometry method that is simple and easy in execution, replicable and meets all the requirements of the State Pharmacopoeia and international standards.</p><p><strong>Findings </strong></p><p>As a result of research, we developed a sensitive, objective, reliable and reproducible method for the spectrophotometric determination of hypertril in the tablet mass.</p><p><strong>References</strong><strong></strong></p><ol><li>Belenichev I.F., Kucherenko L.I., Volchik Yu.A., Abramov A.V., Buhtiyarova N.V. Some aspects of cardioprotective activity of new b-adrenoblocker with NO-mimetic effect «Hypertril» on myocardial infarction model. <em>Farmakolog</em><em>i</em><em>ya ta l</em><em>i</em><em>karska toksikolog</em><em>i</em><em>ya</em> 2014; 4–5 (40): 11-16</li><li>Georgievskiy G.V. Development of the complex physical and chemical methods, ensuring the creation and control of the quality of the original domestic products, 1,2,4-triazole. <em>Zaporozhskiy meditsinskiy zhurnal</em> 2011; 13(1): 58–69.</li><li><em>Derzhavna</em><em> </em><em>Farmakopeia</em><em> </em><em>Ukrainy</em><em> [</em><em>State</em><em> </em><em>Ukrainian</em><em> </em><em>Pharmacopeia</em><em>]. </em>Kharkiv, 2<em>; </em>2008: 620.</li><li>Kucherenko L.I., Hromilova O.V., Moryak Z.B., Tkachenko G.I., Vaschenko O.V. Stage control of tablets manufacturing. <em>Aktualn</em><em>i</em><em> pitannya farmatsevtichnoi </em><em>i</em><em> medichnoi nauki ta praktiki</em> 2014; #2: 31-34.</li><li><em>5. </em>Mazur I.A, Belenichev I.F., Chekman I.S. <em>Using</em><em> 1-(</em><em>β</em><em>-</em><em>phenylethyl</em><em>)-4-</em><em>amino</em><em>-1,2,4-</em><em>triazolium</em><em> </em><em>bromide</em><em> (</em><em>Hypertril</em><em>) </em><em>as</em><em> </em><em>an</em><em> </em><em>active</em><em> </em><em>base</em><em> </em><em>of</em><em> </em><em>drug</em><em> </em><em>preparations</em><em> </em><em>for</em><em> </em><em>correcting</em><em> </em><em>dysfunctions</em><em> </em><em>of</em><em> </em><em>the</em><em> </em><em>nitroxydergic</em><em> </em><em>system</em><em> </em><em>of</em><em> </em><em>target</em><em> </em><em>organs</em><em> </em><em>accompanying</em><em> </em><em>homocysteinemia</em><em> </em><em>and</em><em> </em><em>acute</em><em> </em><em>cerebrovascular</em><em> </em><em>disorders</em><em>.</em> Patent RU 2 532 394, 2013.<em></em></li><li>Mazur I.A, Belenichev I.F., Chekman I.S. <em>Using of 1-(β-phenylethyl)-4-amino-1,2,4-triazolium bromide as an active bast of medical agents for correction of nitroxidergic system dysfunction atherosclerosis and diabetes mellitus</em>. Patent UA 84351, 2013</li><li>Mazur I.A., Chekman I.S., Belenichev I.F., Voloshin N.A. <em>Metabolitotropnyie preparati. Zaporozhe, </em>2007: 304.</li><li><em>European Pharmacopoeia</em>.Strasbourg: Сouncil ofEurope 2007: 1100.</li><li>Sevgi T.U.,Fikriye T.E. Spectrophotometric method for the determination, validation, spectroscopic and thermal analysis of diphenhydramine in pharmaceutical preparation. <em>Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy</em> 2010; 77: 324–329.</li><li>White W.<em> </em><em>Blood</em><em> </em><em>pressure</em><em> </em><em>monitoring</em><em> </em><em>in</em><em> </em><em>cardiovascular</em><em> </em><em>medicine</em><em> </em><em>and</em><em> </em><em>therapeutics</em><em>.</em><em>New</em><em> </em><em>Jersey</em><em>:</em> <em>Humana</em><em> </em><em>Press</em> 2011: 308.</li></ol>

<p><strong>У статті представлений досвід викладання педіатрії у Запорізькому державному медичному університеті, визначені актуальні проблеми оволодіння практичними навичками з педіатрії в умовах кредитно-модульної системи навчання; обґрунтована методика використання поєднання імітаційної та традиційної освіти.</strong></p>

In spite of achievements in the sphere of highly effective drugs creation for treating cardiovascular diseases the problem is still urgent since mortality is high because of these diseases, and it takes the 2-nd – 3-d place among the population of industrially developed countries. In the Research and Production Association “Pharmatron” a new approach concerning creation of new effective anti-anginal drugs has been developed; it is a chemical modification of position 1 and 4 of 1,2,4-triazole molecule by introduction of the structural fragments of the most active medicines and structures imitating sites of adrenergic receptors. Bromides of 1-(alkyl) carboxyalkyl-4-ylideneamino-1,2,4-triazole have been synthesized at the Pharmaceutical Chemistry department of Zaporizhzhia State Medical University under the supervision of professor I.A.Mazur. The cardioprotective activity of 12 compounds – derivatives of 1-carboxyalkyl-4-ylideneamino-1,2,4-triazole bromides and 1-alkyl-4-ylidenamino-1,2,4-triazole bromides has been investigated. The experiments were conducted in 510 white outbred male rats weighing 120-130 g from the mouse bank of the Institute of Pharmacology and Toxicology of the AMS of Ukraine. Determination of acute toxicity of the compounds investigated was conducted according to Kerber method. It has been found that LD50 of these compounds when introduced intraabdominally to rats is within 29.5-295 mg/kg. It allows to refer the compounds under research to the III and IV classes of toxicity (moderate or low toxic). The model of acute myocardial infarction in rats was used for studying the cardioprotective activity of the compounds, the infarction was modeled by staged introduction of isadrin and pituitrin. It has been found that intraabdominal introduction of 8 compounds of 12 ones in the dose of 1/100 LD50 to rats with myocardial infarction leads to decrease of hyperenzymemia of cardiospecific isoenzymes of creatine phosphokinase (MB CPK) and lactate dehydrogenase (LDH-1), which play the role of biochemical markers of the myocardium damage, and decrease of electrophysiological marker ΣΔST during electrocardiography. The structural fragments of the molecule, which play a determinative role in manifestation of the cardioprotective effect of such series as β-phenylethyl, carboxy propyl, octyl in position 1 and the presence of amino- and n-methoxybensilidenamino-groups in position 4, have been revealed. It has been determined that compound MT significantly exceeds the therapeutical efficacy of metoprolol by decrease of MB CPK and LDH-1 activity in the blood serum of rats with myocardial infarction, as well as decrease of ECG ST amplitude.