Low-dose digoxin enhances the anticonvulsive potential of carbamazepine and lamotrigine in chemo-induced seizures with different neurochemical mechanisms

"Non-antiepileptic" drugs have a strong potential as adjuvants in multidrug-resistant epilepsy treatment. In previous study the influence of low doses of digoxin, which do not affect the myocardium, on the anticonvulsant potential of classical commonly used anti-epileptic drugs under conditions of seizures, induced by pentylenetetrazole and maximal electroshock, has been investigated. The aim of the study was to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant potential of carbamazepine and lamotrigine in experimental seizures with different neurochemical mechanisms. Material and methods: A total of 192 random-bred male albino mice weighting 22–25 g were used. Carbamazepine and lamotrigine were administered intragastrically in conditionally effective (ED50) and sub-effective (½ ED50) doses: carbamazepine at doses of 100 and 50 mg/kg; lamotrigine at doses of 25 and 12.5 mg/kg. Digoxin was administered subcutaneously at a sub-cardiotonic dose of 0.8 mg/kg as an adjuvant to carbamazepine and lamotrigine in ½ ED50. Picrotoxin (2.5 mg/kg subcutaneously); thiosemicarbazide (25 mg/kg intraperitoneally); strychnine (1.2 mg/kg subcutaneously); camphor (1000 mg/kg intraperitoneally) were used as convulsant agents. Results: It was found that digoxin not only has its own permanent anticonvulsant effect on different models of paroxysms with different neurochemical mechanisms of development, but also significantly enhances the anticonvulsant potential of carbamazepine (to a lesser extent – lamotrigine) regardless of the pathogenesis of experimental paroxysms. Conclusion: Based on the results, it can be concluded that digoxin has a high potential as an adjuvant medicine in complex epilepsy treatment because it enhances the efficiency of low-dose traditional anticonvulsants carbamazepine and lamotrigine

The main stages of pharmaceutical development of emulgel “Probioskin”

The aim. To conduct research on the pharmaceutical development of a complex preparation with probiotic “Probioskin” in the form of an emulgel for the treatment of infectious and inflammatory dermatological diseases. Methods. Uniformity was determined by visual inspection of the test samples using an XSP-128 ULAB biological microscope. The study of the rheological properties of the samples was carried out using a Rheolab QC rheovisosimeter (Anton Paar, Austria) using a system of coaxial cylinders C-CC27 / SS. Microbiological studies and biotesting on a biological model of ciliates were carried out in aseptic conditions of a laminar box (biological safety cabinet AC2-4E1 “Esco”, Indonesia) of the Department of Biotechnology of the National University of Pharmacy (completely). Pharmacological studies (determination of the parameters of acute toxicity and anti-inflammatory properties on the model of acute exudative inflammation of the foot in rats caused by zymosan and carrageenan) were carried out on the basis of the Central Research Laboratory of the NUPh. Results. On the basis of the complex of the carried out studies, the composition of the complex preparation for skin use “Probioskin” was substantiated. The analysis of the microbiological purity of the developed agent during the proposed shelf life of 12 months showed that the drug meets the requirements of the State Pharmacopoeia Monograph for cutaneous application in terms of the level of microbial contamination by foreign microflora. The complex of pharmacological studies carried out indicates that the drug “Probioskin” can be attributed to group 6 of class and classified as a “relatively harmless” agent. The study of the anti-inflammatory effect of the drug indicates that the drug exhibits moderate anti-inflammatory properties. Under the condition of zymosan inflammation, which is associated with the activation of leukotrienes as inflammatory mediators, the average antiexudative activity of the drug is 33 %. The drug has a moderate antiexudative effect under the condition of carrageenan edema, which is evidence of its effect on exudation processes mediated by prostaglandins. The mean AEA of the study drug was 24 %. Conclusions. For the development of a soft preparation for skin use for the treatment of infectious and inflammatory dermatological diseases, the following components have been selected: active – lactobacilli, dexpanthenol, lactic acid; auxiliary - propylene glycol, peach oil, polysorbate-80, aristophlex, tocopherol, the concentration of which was substantiated on the basis of a complex of organoleptic, physicochemical, pharmacological, microbiological and biological studies. It has been experimentally established that the “Probioskin” emulgel meets the requirements of the SPhU in terms of the level of microbial contamination by extraneous microflora. Pharmacological studies allow the drug to be classified as “relatively harmless” with anti-inflammatory properties at a level not lower than the reference drug

Study of Epilobium angustifolium L. amino acids content by HPLC method

The use of plant raw materials is one of the areas of modern pharmaceutical science in the production of herbal drugs. The genus Epilobium counts more than 200 species, many species of which are used in traditional medicine. Among the Epilobium species, Epilobium angustifolium is one of the well-known medicinal plants which have been used worldwide in habitual medicine. There is insufficient information in the literature on the biologically active substances of Epilobium angustifolium L. The presence of three major polyphenol groups: phenolic acids, flavonoids, and ellagitannins were identified in E. angustifolium extracts. Traditionally, the infusion of leaves of this plant could be useful for headaches, cold and gastrointestinal disorder. The Epilobium angustifolium L. as an insufficiently studied plant is a promising object of study, including amino acids composition. To assess the relationship between the production of primary metabolites and their possible therapeutic properties, we analyzed the amino acid profile of the plant Epilobium angustifolium used in traditional medicine. The study of compounds generated by plants as a result of defense mechanisms permits an understanding of the molecular mechanism involved in their medicinal properties. The aim. Thus, the aim of the study was to conduct an HPLC analysis of the amino acids of E. angustifolium to establish the prospects for the use of the raw materials in medical and pharmaceutical practice. The results of the current study will be used in further breeding programs aimed to obtain an industrial form of E. angustifolium suitable for pharmaceutical and food applications. Materials and methods. The determination of amino acids composition of Epilobium angustifolium was conducted using Agilent 1200 (Agilent Technologies, USA). Results. The HPLC method identified sixteen free amino acids and seventeen bound amino acids in the Epilobium angustifolium herb. The studies have shown that Epilobium angustifolium L. herb is mainly composed of free amino acids such as L-phenylalanine (1.65 µg/mg), L-glutamic acid (1.51 µg/mg), L-arginine (1.24 µg/mg), L-alanine (0.98 µg/mg) and L-aspartic acid (0.57 µg/mg), which were presents in the greatest amount. The dominant bound amino acids in the studied raw material were L-glutamic acid, L-aspartic acid, L-leucine, and L-alanine, the content of which was 32.37 µg/mg, 10.59 µg/mg, 8.70 µg/mg, and 6.22 µg/mg respectively. Conclusions. Using the HPLC method determined the amino acids in the herb of Epilobium angustifolium L. The concentrations of L-aspartic acid, L-glutamic acid, L-arginine, L-alanine and L-phenylalanine are predominate among free and bound amino acids in the Epilobium angustifolium L. herb. The result shows that Epilobium angustifolium L. is the source of amino acids, so the use of this plant raw material for new remedies is possible in the future

Identification of benzydamine and its metabolit in the presence of certain anti-inflammatory non-steroidal drugs

The aim of the work. Currently, a large number of cases of non-medical use of benzydamine hydrochloride have been described. The identification of benzydamine and its metabolite, benzydamine N-oxide, in the presence of some non-steroidal anti-inflammatory drugs, has been insufficiently studied. Therefore, the development of a method for its identification in biological material is an urgent task. Materials and methods. The subjects of the study were benzydamine hydrochloride and its metabolite, as well as some non-steroidal anti-inflammatory drugs, which are its analogues in terms of pharmacological action. The studies were carried out by methods of thin layer chromatography and high-performance liquid chromatography. Results. At the first stage a screening method for benzydamine identification was studied using the extraction in acidic and basic conditions. It was shown that benzydamine can be isolated in both medias with subsequent development with a solution of iodoplatinate and Dragendorff's reagent according to Munier or with Mandelin reagent respectively. The mobile phase was selected and respective hRf for the target molecule were defined. After a preliminary identification of benzydamine a reference method for the final confirmation of the drug that had led to poisoning was proposed. A robust, specific and accurate reversed phase HPLC method was chosen. It was shown that benzydamine exists in biological material mainly in a form of metabolite – benzydamine N-oxide. The selected method was able to separate and determine key analytes in biological samples after a preparative isolation by TLC method. The comparison with UV spectra of the reference standard of benzydamine hydrochloride was proposed to avoid false positive conclusion of drug identification. Conclusions. Proposed methodology can be applied for routine identification of benzydamine poisoning in toxicological laboratories

Results of public assessment of influence factors on the formation of the brand of the institution of higher education in the pharmaceutical direction

The aim of the article is to study the attitude of target audiences to the brand of a higher education institution, taking into account the specifics of the educational services provided to them and the specifics of the educational services market. Methods of the research: theoretical (analysis and synthesis of scientific literature and normative sources, generalization, analytical, comparative and logical), empirical (descriptions, comparison, questionnaires, mathematical and statistical). Materials: questionnaires of respondents, which were applicants, students, alumni and employees of NUPh. Results of the research. According to students, the most significant factors are positive reviews about HEI (14 % of respondents), the quality of educational services and the involvement of well-known scientists and practitioners (12 % each), the presence of scientific schools, traditions and the active participation of the institution in public life (11 % each factor). For applicants, an important place is occupied by the state status of a higher education institution, positive reviews about it and high quality of educational services (13 % for each factor). The advantages that graduates of the prestigious HEI have after graduation are a high level of theoretical knowledge (89 % of respondents) and practical skills (85 %), a high level of competitiveness in the labor market (81 %). Among the main directions for the development and improvement of the educational brand, the interviewed NUPh employees noted the constant improvement of the quality of educational services (91 % of the respondents), the intensification of international cooperation (86 %), the active involvement of practitioners and scientists in the scientific, volunteer and cultural life of the institution (79 %). Conclusions. It has been proven that an important component of the brand of a higher education institution is an educational service; image of educational services; the benefits to be provided by the brand owner to consumers of educational services. The most significant factors of popularity and positive attitude towards NUPh and the advantages received by graduates after graduation have been established. A conclusion was made about the high level of corporate culture in HEI, the important elements of which are the presence of the NUPh development strategy, the introduction of effective management technologies and the creation of conditions for the self-realization of employees

Substantiation of technological parameters of the oil extract obtained from Urtica dioica roots based on the yield determination of phytosterols using capillary gas chromatography method

Due to the content of phytosterols, extractive preparations of Urtica dioica roots are able to show antiandrogenic effect in the case of external therapy of men and women with androgenic alopecia. Oil extracts (OE) are characterized by several advantages when applied to the skin of the scalp compared to water-alcohol extracts. For the development of OE technology from Urtica dioica roots, it is important to choose the optimal extraction parameters, which are based on the quantitative determination of phytosterols in the extractant and the studied samples of extracts. The aim of the work is to choose the optimal parameters for obtaining OE from Urtica dioica roots based on quantitative determination of phytosterols content in experimental samples of OE by gas capillary chromatography. Materials and methods. Objects of the research – Urtica dioica root, refined corn oil, refined sunflower oil, samples of oil extracts. Determination of phytosterol content in experimental samples was carried out by gas capillary chromatography (chromatograph “Crystal 2000”, manufacturer – research and production company “Analytics”). Results. 5 different compounds of steroid structure (stigmasterol, β-sitosterol, etc.) were identified in sunflower oil by gas liquid chromatography, and 10 (campesterol, 2-α stigmasterol, β-sitosterol, Δ5-avenosterol, etc.) were identified in sunflower oil. The quantitative content of β-sitosterol in the sum of sterols of corn oil was significantly higher compared to the content of this substance in sunflower oil and amounted to 59.33 %. Optimal technological parameters were established considering the peculiarities of extraction with oil extractant and quantitative determination of the amount of phytosterols and β-sitosterol in experimental samples of OE. The total content of plant sterols in OE, including considering their amount in the extractant, was in the range of 7880 mg/kg; the amount of β-sitosterol was 4638 mg/kg. Conclusion. The choice of optimal parameters for obtaining OE from UDR based on determination of phytosterol yield by gas capillary chromatography was experimentally substantiated, namely: extractant – corn oil, raw material-extract ratio – 1: 5, extraction time – 6 h, extraction method – maceration

Screening study of the antihyperglycemic action of new solid quercetin dispersions

The aim – to screen new solid dispersions of quercetin for the presence of antihyperglycemic action and to identify the most active substances that are promising for the creation of antidiabetic drugs. Materials and methods. The object of the study was 4 new solid dispersions of quercetin, developed at the National University of Pharmacy. Solid dispersions of quercetin were prepared by the liquid-phase method; hydroxypropyl methylcellulose (HPMC) or polyvinylpyrrolidone (PVP) in ratios of 1:1 and 1:2 were used as a carrier. The antihyperglycemic effect of the studied substances at a dose of 50 mg / kg was assessed in rats by the ability to lower blood glucose levels after carbohydrate loading in a model of impaired glucose tolerance induced by dexamethasone and in experimental type 2 diabetes mellitus induced by dexamethasone. Results. It was found that with impaired glucose tolerance, a solid dispersion of quercetin with HPMC (1:1) showed a pronounced antihyperglycemic effect – the glucose level 30 minutes after glucose load significantly decreased by 28 % and did not differ from the action of metformin, which was confirmed by the value of the area under glycemic crooked. When solid dispersions with PVP (1:1 and 1:2) were used, the antihyperglycemic effect was less pronounced. In a model of type 2 diabetes mellitus, a significant antihyperglycemic effect was found only in a solid dispersion of quercetin with HPMC (1:1) at the metformin level, which indicates an increase in the solubility and absorption of quercetin. Conclusions. A pronounced antihyperglycemic effect at the metformin level was found in a solid dispersion of quercetin with HPMC in a 1:1 ratio with impaired glucose tolerance and type 2 diabetes mellitus. It has been proven that a solid dispersion of quercetin with HPMC is a promising substance for creating a monocomponent drug or for inclusion in a new antidiabetic combined drug

Interaction of surfactants with poloxamers 338 and its effect on some properties of cream base

The aim. Study of the interaction of surfactants with poloxamer 338 (P338) and the effect of P338 on the properties of cream bases. Materials and methods. Solutions of the surfactants and P338 as well as cream bases were under study. The average hydrodynamic diameter (Dh) and zeta potential (ζ‑potential) were determined by the light scattering intensity and electrophoretic mobility of micelles. The electron paramagnetic resonance (EPR) spectra of spin probes in micelles, solvents and bases were obtained; the type of spectrum, isotropic constant (AN), rotational correlation times (τ) and anisotropy parameter (ε) were determined. Liquids and cream bases were studied by capillary and rotational viscometry; the flow behaviour and yield stress (t0), dynamic and apparent viscosity (η) as well as the hysteresis (thixotropic) area (AH) were determined. The microstructure of the bases was examined by optical microscopy. The strength of adhesion (Sm) was assessed by the pull-off test, and the absorption of water was studied by dialysis. Results. Under the impact of P338 the hydrodynamic diameters of micelles formed by cationic, anionic and nonionic surfactants decreased as well as the absolute values of their ζ‑potential became lower, but the microviscosity of the micelle nuclei increased. There was also a change in the structure of the aggregates of surfactant with fatty alcohols; EPR spectra, which were superpositions characteristic for the lateral phase separation, converted into triplets that indicated the uniform distribution of lipophilic probes in the surfactant phase. When the content of P338 increased to 17 %, the rheological parameters of the bases increased drastically, the flow behaviour and the microstructure changed. The bases had the consistency of cream within temperature range from 25 °C to 70 °C and completely restored their apparent viscosity, which had decreased under shear stress. P338 enhances the adhesive properties of the bases. Due to their microstructure, cream bases have a lower ability to absorb water compared to a solution and gel containing 17 % and 20 % P338, respectively. Conclusions. The structure of surfactant micelles and aggregates of surfactants with fatty alcohols changed under impact of P338 due to the interaction of surfactants with P338. As a result of this interaction, at a sufficiently high concentration of P338, the microstructure and flow behaviour of bases changed, their rheological parameters, which remain high at temperatures from 25 °C to 70 °C, increased significantly, and water absorption parameters decreased. The bases with P338 were more adhesive

Synthesis and antibacterial activity of 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a] azepin-1-ium bromides and aryl-(4-R1-phenyl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulen-1-ylmethyl)-amines

The aim of this work is to develop methods of synthesis of 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromides and aryl-(4-R1-phenyl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulen-1-ylmethyl)-amines and to study their antimicrobial activity against strains of gram-positive and gram-negative bacteria as well as yeast fungi. Materials and methods. 1Н NMR spectra were recorded on Bruker 400 spectrometer operating at frequency of 400 MHz. Antimicrobial activity of the compounds synthesized was evaluated by their minimum inhibitory concentration (MIC) values. Results and discussion. The interaction of 3-arylaminomethyl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepines with substituted phenacyl bromides produced novel 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromides. The latter when refluxed in 10 % solution of NaOH gave aryl-(4-R1-phenyl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulen-1-ylmethyl)-amines. The study of antimicrobial activity of the compounds obtained allowed to find derivatives which are active against С. albicans and S. aureus strains. Among the compounds tested 3-[(41-bromophenylamino)-methyl]-1-[2-(4-methoxyphenyl)-2-oxoethyl]-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromide 5cd appeared to be more active than the reference drug Cefixime and displayed close antimicrobial activity as the antibiotic Linezolid. Conclusions. It was found out that derivatives of 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromides display broad spectrum of antimicrobial activity and are able to inhibit growth of both bacteria and fungi. S. aureus and C. albicans turned out to be the most sensitive strains to the compounds tested, MIC was in the range of 6.2-25.0 mg/mL. Gram-negative strains of microorganisms were less sensitive to the compounds evaluated and 5fа was the most active derivative displaying antimicrobial activity at the concentration of 50.0 mg/mL. Antimicrobial activity of triazoloazepinium bromide derivatives was similar to that one of Linezolid and Fluconazole reference drugs and more pronounced than the activity of Cefixime. Hence, the data gathered evidence the feasibility of further study of the antimicrobial properties of the most active compounds in in vivo experiments aiming at assessment of the prospects for the creation of new effective and safe antimicrobial drugs based on them

Study of compatibility of components of a new combined drug for treatment of alcoholic intoxication and its hepatoprotective effect on a model of alcoholic liver injury

The aim of the work is the development of a combined drug for use in alcohol intoxication based on the physicochemical properties and chemical compatibility of active pharmaceutical ingredients and excipients, and the study of the hepatoprotective effect in alcoholic hepatitis in rats. Materials and methods. During the studies, physical and physicochemical methods were used, a Specord 200 spectrophotometer (Germany), analytical scales Sartorius (SARTORIUS, Germany), class A volumetric glassware and reagents that meet the requirements of the State Pharmacopoeia of Ukraine (SPhU). Alcoholic hepatitis in rats was reproduced by intragastric administration of an aqueous 40% ethanol solution at a dose of 7 ml/kg for 1 week. Results. A new combined agent is proposed for use in alcohol intoxication in the form of an effervescent powder for the preparation of an oral solution, which contains glycine, L-glutamic acid, acetylsalicylic acid, ascorbic acid, fructose / sorbitol and sodium bicarbonate and citric acid to accelerate the dissolution of medicinal substances. To study the compatibility of the components, experimental studies of hygroscopicity, chemical interaction / chemical stability and an assessment of the redox potential of the proposed active pharmaceutical ingredients were carried out. To study the stability of the API, studies were carried out on sugaramine condensation due to the choice of amino acids and ascorbic acid in the composition of drugs. Based on the research results, it was decided to divide the API into 2 packages, separating sodium bicarbonate and glycine, which can interact with ascorbic acid / acetylsalicylic acid and ascorbic acid, respectively. In an in vivo experiment, it was found that the use of the new drug is accompanied by the normalization of the antioxidant-prooxidant status of the liver due to a likely decrease in the TBA-AP level and an increase in the RG index in the liver homogenate relative to the control group. Conclusions. Evaluation of the physicochemical properties of API allowed us to propose a new combined drug (TS-PP) for use in alcohol intoxication in the form of an effervescent powder for the preparation of oral solution. In alcoholic hepatitis in rats, it was found that the use of the studied drug largely prevents the formation of the effects of the toxic effects of ethanol on the rat organism, which is manifested by inhibition of destruction of hepatocyte membranes, a decrease in the level of LPO products, restoration of the RG index and improvement of the protein synthesizing function of the liver due to the complex effect of amino acids and ascorbic acid contained in the product