One of the most common eye diseases is a burn injury. Hence, one of the pressing challenges in the field of pharmacy today is the development of new ophthalmic medications, specifically eye drops. Researchers from the Department of Pharmaceutical, Organic, and Bioorganic Chemistry at Zaporizhzhia State Medical and Pharmaceutical University, led by Professor I. A. Mazur, have successfully synthesized a novel compound. This compound is a derivative of 1,2,4-triazole, specifically (S)-2,6-diaminohexanoic acid 3-methyl-1,2,4-triazolyl-5-thioacetate. Notably, this compound demonstrates anti-inflammatory, wound-healing, and reparative activities. The aim of the work is to develop a method of quantitative determination of the active substance in Angiolin eye drops by the method of high-performance liquid chromatography. Materials and methods. The research employed a liquid chromatograph equipped with a UV detector. A column Hypersil ODS C-18 measuring 250 by 4.6 millimeters with a particle size of 5 microns was used. Results. It was determined that the angiolin content in the 1 % eye drops in series 1 falls within the range of 0.985 to 1.010 grams. This indicates that, in terms of the active substance content, the studied series complies with the requirements of the State Pharmacopoeia of Ukraine. Conclusions. As a result of the conducted research, a method for quantitatively determining the active substance in Angiolin eye drops using high-performance liquid chromatography was developed.

Today, the important problem is the creation of new decamethoxine and thiotriazoline based drugs for the treatment of stomatitis. The aim of the work is to develop a method for quantitative determination of decamethoxine and thiotriazoline in the model mixture (1:25) by spectrophotometry. Materials and methods. Series 6 model mixtures were made at the ratio of decamethoxine and thiotriazoline 1:25. We used certified substances: thiotriazoline series GTT 3460911 (manufacturer: State Enterprise Chemical Reagents Plant, Kharkiv), decamethoxine series № 010915 (manufacturer: LLC “PHARMCHIM”). Optizen POP spectrophotometer, polyvinyl alcohol, hydrochloric acid, and eosin were used. Results. A method for quantitative determination of decamethoxine and thiotriazoline in MS was developed. It was established that the content of active substances in MS is thiotriazoline from 0.5021 to 0.5096, decamethoxine from 0.0207 to 0.0211. Conclusions. A method for quantitative determination of decamethoxine and thiotriazoline in MS has been developed. The method of quantitative determination of decamethoxine and thiotriazoline in MS is reproducible.

Throughout human history, cataracts have been one of the leading causes of blindness. For this disease, we studied the market of drugs of domestic and foreign production. The object of our study was the subgroup S10X Other ophthalmic drugs. Employees of the Department of Pharmaceutical Chemistry of Zaporizhzhia State Medical University (ZSMU) together with specialists of the NGO “Pharmatron” was synthesized a new compound, which was named Angiolin. A rational dosage form in the form of eye drops was proposed for the new drug. Since the drops continue to be the most common and widely used in practice dosage form. We have previously selected the optimal content of the active substance in eye drops. As is known from the technological parameters, eye drops must be isotonic, ie in their composition should be added excipients. The aim of our work is to select the concentration of excipients for the manufacture of eye drops Angiolin. Materials and methods. During the work at the Department of Pharmaceutical Chemistry of ZSMU, three solutions of eye drops Angiolin with different composition were prepared, and later the theoretical osmolarity was calculated. Results. Accurate theoretical calculation of the osmolarity of solutions containing substances with high molecular weight, complex total extracts, and highly concentrated solutions is impossible. Since the excipient was used methylcellulose, it was better to perform such a calculation experimentally, through the determination of osmolality. On the basis of the conducted researches, for correction of osmolarity, we were chosen – sodium chloride. Sodium chloride was selected at a concentration of 7.0 g/l, which creates an osmolality of the drug equal to 234.3 mosmol/kg. The estimated value at the same concentration of sodium chloride was 239.56 mosmol/l. The value of osmolarity of eye drops was calculated from it makes 302,18 mosmol/l that was confirmed the correctness of the chosen concentration of sodium chloride as a part of eye drops. Conclusions. Based on the above, we selected the concentration of excipients for the manufacture of eye drops Angiolin.

Мета роботи. Розробка складу та технології таблеток гамма-аміномасляної кислоти з тіотриазоліном. Матеріали і методи. В роботі використовували гамма-аміномасляну кислоту (Sigma-Aldrich, США); тіотриазолін (Державне підприємство «Завод хімічних реактивів» Науково-технологічного комплексу «Інститут монокристалів» НАН України), допоміжні речовини вітчизняного і закордонного виробництва. Таблетки ГАМК з тіотриазоліном готували методом вологої грануляції. Пресували таблетки за допомогою лабораторного таблеткового пресу 6000S (Білорусь) з діаметром пуансонів 10 мм та контролювали їх фармако-технологічні властивості. Результати й обговорення. Для вивчення трьох факторів використовували латинський квадрат третього порядку. Вивчали вплив природи допоміжних речовин на зовнішній вигляд таблеток, однорідність маси, стираність, розпадання та стійкість до роздавлювання. За результатами експериментальних досліджень проводили дисперсійний аналіз експериментальних даних та робили висновки про вплив вивчених факторів на показники якості таблеток ГАМК з тіотриазоліном. Висновки. За результатами проведених досліджень вивчили вплив трьох факторів допоміжних речовин на зовнішній вигляд, однорідність маси, стираність, стійкість до роздавлювання та розпадання таблеток. Дисперсійний аналіз результатів дозволив вибрати кращі ДР (МКЦ 301, 3 % розчин МЦ 100, магнію стеарат), які забезпечують фармакопейні фармако-технологічні вимоги, що висуваються до таблетованих лікарських форм.

The modern strategy of potential biologically active molecules search (“drug-design”) is based on several innovation approaches. The method of high thrоughрut biological screening and method of molecular modeling deserves the most attention among such approaches. Lipoxygenase (LOX) is one owf the most perspective biological target for the substituted pyrrolo[1,2-a][1,2,4]triazolo-(triazino-)[c]quinazolines. So, molecular docking towards LOX and enzyme activating activity was investigated. The aim: Directed search of potential inhibitors of lipoxygenases among the unknown pyrrolo[1,2-a][1,2,4]triazolo-(triazino-)[c]quinazolines with the use of molecular docking and in vitro high throughput screening. Materials and methods. The research of lipoxygenase activity has been conducted for a number of original pyrrolo[1,2-a][1,2,4]triazolo-(triazino-)[c]quinazolines. Standard software was used for molecular docking and “drug-like” criteria research. Sodium letinate was used as a substrate to study soybean LOX enzyme activating activity. Results. The results of molecular docking have shown, that substituted pyrrolo[1,2-a][1,2,4]triazolo[1,5-c]quinazolines reveal a strong affinity toward LOX. The main types of interactions with aminoacid residues of mentioned the enzyme were identified. The conducted researches showed, that the substituted pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazolines had the highest soybean LOX inhibition activity. Compounds with a fluorine atom and a 2-thienyl moiety in the structure revealed the highest activity inhibiting lipoxygenase by 36.33 % and 39.83 % respectively. The increased lipophilicity of triazine derivatives promotes a higher ability to inhibit soybean LOX, whereas, for triazole derivatives, which have lower molecular weight, an inverse relation is observed. Conclusions. The research of the substituted pyrrolo[1,2-a][1,2,4]triazolo-(triazino-)[c]quinazolines inhibition ability of soybean LOX as one of the possible mechanisms of their activity is proved and conducted. It is shown, that their lipoxygenase activity depends on lipophilicity and is defined by the availability of donor-acceptor fragments in the molecule, that is capable to form hydrogen and other types of interaction. The specified results are strong arguments for their further study as promising anti-inflammatory agents.

Today, diseases caused by pathogenic bacteria are the most dangerous, as they can not only affect the quality of human life, but also lead to death. According to the WHO, pathogenic bacteria namely, mycoses affect from 1/5 to 1/3 of the world's population, more than a third (37.8 %) of them cause yeast-like (Candida). Over the past 20 years, there has been a 15-fold increase in the frequency of infectious inflammatory diseases of candidiasis etiology. After examining the range of drugs on the pharmaceutical market of Ukraine and abroad, it was found that the following drugs of foreign origin are currently used for the treatment of these diseases: Methyluracil (Lekhim, Ukraine), Solkoseril (Birsfelden, Switzerland), Mexidol (PHARMASOFT, Moscow, RF). Based on the above it is seen that the range of drugs for the treatment of oral mucosa diseases is limited. All of the above shows the need for the creation of a new domestic drug exhibiting antimicrobial, fungicidal, reparative activity. The aim of our work is to create a new drug based on the model mixture of Thiotriazoline and Decamethoxinum, which exhibit antimicrobial, fungicidal, repertoire activity. Materials and methods. Thiotriazoline, decamethoxinum, model mixture. The studies were carried out by agar diffusion (well method) to study antimicrobial activity. Model mixtures with decamethoxinum were made from 0.5 to 5 mg; thiotriazoline – 200 mg. Antimicrobial activity of these model mixtures was carried out. Results. The model mixture of thiotriazoline and decamethoxinum in antimicrobial and fungicidal action was significantly superior to decamethoxinum by 54 % in the degree of growth inhibition of S. aureus, by 120 % in the degree of growth inhibition of E. coli, by 57 % in the degree of growth inhibition of P. aeruginosa, and by 108 % in the degree of growth retardation of C. albicans at 106 CFU/ml of medium. Conclusion. The model mixture of thiotriazoline and decamethoxinum exhibits high antimicrobial and fungicidal activity.

The aim of work. To develop standardization methods the model mixture, which consists of L-tryptophan and thiotriazoline in the therapeutic ratio 4:1. Materials and Methods. During the study, 6 series of the model mixture of L-tryptophan and thiotriazoline in a ratio of 4:1 (the active ingredient content per tablet 200 mg and 50 mg respectively) were prepared in the laboratory and was developed the standardization method for their simultaneous determination by HPLC. Results and Discussion. An analysis of 6 series of a model mixture (in each of 6 experiments) was carried out according to the developed HPLC method. As a result of the study, we have determined the content of L-tryptophan, which is from 197.2 mg to 204.9 mg, thiotriazoline from 48.9 mg to 50.5 mg, that meets the requirements of the current normative documentation. Results. In the course of work, we have developed a high-sensitivity, reproducible, reliable, high-precision method of simultaneous standardization of active substances, which is planned to be used for the stage-by-stage control of the quality of L-tryptophan and thiotriazoline tablets.

Мета роботи. Розробка методів стандартизації модельної суміші, до складу якої входять L-триптофан та тіотриазолін у терапевтичному співвідношенні 4:1.Матеріали і методи. У ході дослідження в лабораторних умовах виготовлено 6 серій модельної суміші L-триптофану та тіотриазоліну в співвідношенні 4:1 (вміст діючих речовин на одну таблетку 200 мг і 50 мг відповідно) та розроблено методику стандартизації їх одночасного визначення методом ВЕРХ.Результати й обговорення. Проведено аналіз 6 серій модельної суміші (в кожній по 6 дослідів) за розробленою методикою ВЕРХ. У результаті дослідження визначили вміст L-триптофану, який становить від 197,2 до 204,9 мг, тіотриазоліну від 48,9 мг до 50,5 мг, що відповідає вимогам чинної нормативної документації.Висновки. У ході роботи розроблено високочутливий, відтворюваний, надійний, високоточний метод одночасної стандартизації діючих речовин, який планується використовувати при постадійному контролі якості таблеток з L-триптофаном та тіотриазоліном.

Introduction. According to current legislation of Ukraine the specifications of tablets include the following indicators: description, identification, average weight, disintegration and assay. The aim of the study. The development of specifications and project of quality control methods for "Karbatril" codenamed tablets. Materials and methods. During the study we analyzed 6 series of tablets "Karbatril." For the description, identification, determination of the average mass, disintegration, active ingredients quantify of "Karbatril" codenamed tablets we used appropriate methods and instruments. Results and discussion. Tablets "Karbatril" were analyzed for the following parameters: - Overview - Tablets white or nearly white; - Average weight - during the study the average weight of 6 series of obtained tablets ranged from 339,0 mg to 369,9 mg according to SPU from 337,0 mg to 373,0 mg; - Disintegration – according to SPU the disintegration for tablet without shell shall not exceed 15 min. Analyzed tablets disintegrated in the period from 5 to 10 minutes; - Identification and quantification of the active ingredients of tablets were conducted using modified HPLC methods. During the identification obtained chromatograms show compliance with SPU. In quantitative determination of the active ingredients content in "Karbatril" codenamed tablets we found carbamazepine from 148.18 mg to 150.19 mg, thiotriazoline - from 98.93 mg to 99.71 mg. This data is consistent to SPU which regulates content of carbamazepine - 150 mg ± 7,5%, thiotriazoline - 100 mg ± 10%. Conclusions. This study has developed specification for "Karbatril" codenamed tablets and also methods of HPLC qualitative and quantitative determination of active ingredients. In the specification the following parameters are included: description, identification, average weight, disintegration and assay. The study drafted quality control methods which are planned to be later offered to the manufacturer.

The aim of the work.Creation of new tablet drug with neuropsychotropic effect based on L-tryptophan and thiotriazoline, selection of optimal excipients, study of their effect on the pressing process, surface quality and uniformity of the tablet dosing mass. Materials and Methods.The active substances are L-tryptophan and thiotriazoline in a 4:1 ratio, excipients (fillers, disintegrants, binding solutions, solubilizers).The tablets were compressed by wet granulation.The effect of the excipients on tablets containing L-tryptophan and thiotriazoline was studied according to the following parameters: uniformity of the tablet dosing mass, pressing process, appearance of tablet surface after production. Results and Discussion.According to the results of ANOVA of the experimental data, it was found that the nature of the fillers, disintegrants, binding solutions, solubilizers influences the pressing process, the appearance of the surface of the tablets after production, and the uniformity of the tablet dosing mass with L-tryptophan and thiotriazoline. For example, the mixture of such explosives as MCC 101+potato starch+neusilin UFL has the best influence among fillers on the process of tablets pressing, sodium starch glycolate is the leader among disintegrants. The quality of the surface of L-tryptophan tablets with thiotriazoline after production is most favorably affected by the mixture of MCC 101+potato starch+basic magnesium carbonate among disintegrants. The 5% solution of hydroxypropymethylcellulose 5 is the leader for uniformity of the tablet dosing mass among binders, the advantage is on the side of the polyplasdone XL 10 among disintegrants, the mixture of MCC 101+potato starch+magnesium carbonate is the main one among the fillers, aerosil is the most influential among the solubilizers. Results.The effect of four groups of excipients on the uniformity of dosing, the pressing process and the appearance of tablets with L-tryptophan and thiotriazoline was studied.Most of the 16 studied excipients are suitable for tableting based on L-tryptophan and thiotriazoline by wet granulation.The diagrams of the advantages of the levels of 4 investigated factors were made from the studied parameters (pressing process, surface quality of tablets, uniformity of dosing). Conclusions. The rational selection of excipients to obtain tablets based on L-tryptophan and thiotriazoline by wet granulation method was carried out. The influence of excipients on uniformity of dosing, the pressing process and the appearance of L-tryptophan and thiotriazoline tablets obtained by wet granulation, was considered.

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 ß1- 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 1. The effect of six excipients groups on technological characteristics of hypertril’s powder masses is studied. 2. In most series of experiments, powder masses have technological properties that indicate the possibility of tablets’ creating by direct pressing. References 1. Belenychev Y.F. Nekotorye aspekty kardyoprotektornoho deystvyya novoho b-adrenoblokatora s NO-mymetycheskym éffektom «Hypertryl» na modely ynfarkta myokarda / Belenychev Y.F., Kucherenko L.Y., Volchyk YU.A., Abramov A.V., Bukhtyyarova N.V // Farmakolohiya ta likarsʹka toksykolohiya.- 2014. - № 4–5 (40) – C. 11-16. 2. Derzhavna Farmakopeya Ukrayiny / DP "Naukovo-ekspertnyy farmakopeynyy tsentr". - 1-e vyd. - Kharkiv: "RIHER", 2001. - 556s. 3. Mazur Y.A., Belenychev Y.F., Chekman Y.S. y dr. Prymenenye bromyda 1-(beta-fenylétyl)-4-amyno-1,2,4-tryazolyya (Hypertryl) kak aktyvnoy osnovy lekarstvennykh sredstv dlya korrektsyy narushenyy funktsyonyrovanyya nytroksyderhycheskoy systemy orhanov-mysheney pry homotsysteynemyy y ostrykh narushenyyakh moz·hovoho kroobrashchenyya. Patent 2532394 Rossyyskaya Federatsyya. MPK A61K31/4196 (2006.01) A61P9/10 (2006.01) A61P43/00 (2006.01). Zayavytelʹ y patentoobladatelʹ OOO NPO «Farmatron». - № 2013148306. Zayavl. 29.10.2013, opubl. 10.11.2014. 4. Mazur I.A., Byelyenichev I.F., Chekman I.S. ta in. Zastosuvannya bromidu 1-(b-feniletyl)-4-amino-1,2,4-tryazoliyu yak aktyvnoyi osnovy likarsʹkykh zasobiv dlya korektsiyi porushenʹ funktsionuvannya nitroksyderhichnoyi systemy pry aterosklerozi i tsukrovomu diabeti. Patent 84351 Ukrayina. MPK A61K 31/41 (2006.01), A61P 9/10 (2006.01). Zayavnyk i patentovlasnyk TOV NVO «Farmatron». - № a201212500. Zayav. 02.11.2012, opubl. 25.10.2013. 5. Mazur Y.A. Metabolytotropnye preparaty / Mazur Y.A., Chekman Y.S., Belenychev Y.F., Voloshyn N.A. y dr. – Zaporozhʹe, 2007. – 304 s. 6. Matematychne planuvannya eksperymentu pry provedenni naukovykh doslidzhenʹ v farmatsiyi / [Hroshovyy T.A., Martsenyuk V.P., Kucherenko L.I. ta in.] – Ternopilʹ: Ukrmedknyha, 2008. – 368 s. 7. Beckett N.S., Peters R., Fletchers A.E. et al. Treatment of Hypertension in Patients 80 Years of Age or Older// N Engl J Med. 2011; 358:1887–1888. 8. Coca A. Cerebral involvement in hypertensive cardiovascular disease// Eur. Heart J. 2010; 5 (Suppl): F19–25. 9. Dahlof B., Devereux R.B., Kjeldsen S.E. et al. Cardiovascular morbidity and mortality in the Losartan Intervention For End point reduction in hypertension study (LIFE): frandomized trial against atenolol// Lancet. 2002; 359:995-10-03.

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 tablets «Hypertril» N. V. Parnyuk, L. I. Kucherenko, O. O. Portna Zaporizhian State Medical University Scientific-and-Production Corporation «Pharmatron», Zaporizhzhia Introduction Despite the variety of serious diseases which are relevant to the modern world, cardiovascular diseases remain the leading causes of death in the world. Proper treatment and competent prevention of cardiovascular diseases will help reduce the number of patients suffering from coronary disease, strokes and other ailments. Staff members of SPA Farmatron (Zaporizhzhia) in collaboration with the Department of Pharmaceutical Chemistry of Zaporizhzhia State Medical University under Professor Mazur I.A. synthesized new original hypertril medication (bromide 1-(β-phenylethyl)-4-amino-1,2,4-triazole), which shows antihypertensive, antiischemic and antioxidant properties. After preclinical studies we have established ED 50 for animals and predicted human advisability of taking 20 mg of hypertril per reception. Thus the development of technology of tablet dosage form containing 20 mg of active substance became a burning issue of today. Objective. Development of technology of Hypertril tablets by direct pressing on the basis of selection of rational excipients. Methods. In previous studies, we have studied six excipients groups which possess different physical and technological properties. In this paper, we concentrate on the study of the effect of different excipients groups on pharmaco-technological properties hypertril tablets. One tablet contained0.02 g of hypertril,0.082 g sample of microcrystalline cellulose (factor A),0.040 g of sugar sample (factor B),0.010 g of disintegrant (factor C),0.040 g of crystalline substances (factor D),0,006 grams of glidants (factor E) and0.002 g of 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. The results of experimental studies were analyzed by analysis of variance upon which we concluded studied impact of factors on the technological properties of hypertril tablets. Results and discussion. The results of analysis of variance showed that only factor A affects the process of pressing of Hypertril tablets under statistical insignificance of the other five factors. All six factors affect the uniformity of tablets weight in the following order: D> A> C> F> E> V, tablets strength - A> E> D> F> B> C, tablets abrasion: A > D> C> F> B> E, tablets disintegration - C ˃ F ˃ in ˃ D ˃ E ˃ A. The conducted researches have shown that studied six groups of excipients manifest leaders in effect on one or another technological tablets index. As a result of the conducted researches the rational excipients, which made it possible to offer optimal composition of Hypertril tablets, were chosen. Findings The effect of six excipients groups on technological characteristics of hypertril tablets is studied and the possibility of their receiving by straight pressing was proved. As a result of complex pharmaco-technological researches an optimal composition of new Hypertril tablet medication with 20 mg of active substance was developed. References Belenychev Y.F. Nekotorie aspekti kardyoprotektornoho deystvyya novoho β-adrenoblokatora s NO-mymetycheskym ehffektom «Hypertryl» na modely ynfarkta myokarda / Belenychev Y.F., Kucherenko L.Y., Volchyk Yu.A., Abramov A.V., Bukhtyyarova N.V // Farmakolohiya ta likars'ka toksykolohiya. - 2014. - # 4–5 (40) – C. 11-16. Derzhavna Farmakopeya Ukrayiny / DP Naukovo-ekspert¬nyy farmakopeynyy tsentr. - 1-e vyd. - Kharkiv: RIHER, 2001. - 556s. Mazur Y.A., Belenychev Y.F., Chekman Y.S. y dr. Prymenenye bromyda 1-(beta-fenylehtyl)-4-amyno-1,2,4-tryazolyya (Hypertryl) kak aktyvnoy osnovy lekarstvennykh sredstv dlya korrektsyy narushenyy funktsyonyrovanyya nytroksyderhycheskoy systemi orhanov-mysheney pry homotsysteynemyy y ostrykh narushenyyakh mozhovoho kroobrashchenyya. Patent 2532394 Rossyyskaya Federatsyya. MPK A61K31/4196 (2006.01) A61P9/10 (2006.01) A61P43/00 (2006.01). Zayavytel' y patentoobladatel' OOO NPO «Farmatron». - # 2013148306. Zayavl. 29.10.2013, opubl. 10.11.2014. Mazur I.A., Byelyenichev I.F., Chekman I.S. ta in. Zastosuvannya bromidu 1-(β-feniletyl)-4-amino-1,2,4-tryazoliyu yak aktyvnoyi osnovy likars'kykh zasobiv dlya korektsiyi porushen' funktsionuvannya nitroksyderhichnoyi systemy pry aterosklerozi i tsukrovomu diabeti. Patent 84351 Ukrayina. MPK A61K 31/41 (2006.01), A61P 9/10 (2006.01). Zayavnyk i patentovlasnyk TOV NVO «Farmatron». - # a201212500. Zayav. 02.11.2012, opubl. 25.10.2013. Matematychne planuvannya eksperymentu pry provedenni naukovykh doslidzhen' v farmatsiyi / [Hroshovyy T.A., Martsenyuk V.P., Kucherenko L.I. ta in.] – Ternopil': Ukrmedknyha, 2008. – p. 368. Parnyuk N.V. Vybir ratsional'nykh dopomizhnykh rechovyn z metoyu stvorennya tabletok «Hipertryl» metodom pryamoho presuvannya Povidomlennya 1. «Doslidzhennya vplyvu dopomizhnykh rechovyn na tekhnolohichni kharakterystyky poroshkovykh mas» / Parnyuk N.V., Kucherenko L.I., Portna O.O.// Farmatsevtychnyy chasopys – 2015, # 4 – S. 19-24. 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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.

The article presents the dynamics of development of qualitative and quantitative composition of correspondence pharmacy students in Zaporozhye State Medical University. The question of organization of educational-methodical work at the faculty in conditions of credit-module system was considered. Proposals on introduction of new information technologies in educational process were given.