Anti-exudative Effect Research Articles

ASSESSMENT OF PHARMACOLOGICAL ACTIVITY OF THE FLAVONOID FRACTION OF THE HERBS SERPUHA CORONANA

Introduction. It is urgent to search for plants that can become sources of biologically active substances for the creation of new highly effective and safe medicines. One of these plants is the crowned sickle (Serratula coronata L.). The value of crowned serpuha is determined by its high content of phytoecdysteroids and flavonoids. The purpose of the work is to study the acute toxicity, anti-inflammatory activity and capillary-strengthening effect of the flavonoid fraction of the herb Serpucha crown. Material and methods. In the Department of Experimental Pharmacology of the Federal State Budgetary Institution VILAR, a study of the pharmaco-logical activity of the flavonoid fraction of the herb Serpucha crowned was carried out. Acute toxicity parameters were assessed using the Kerber method. The toxicity class of the test substance was determined according to GOST 12.1.007-76 "Harmful substances. Classification and general safe-ty requirements." The anti-inflammatory effect of the flavonoid fraction of the herb Serpucha crown was studied in models of formaldehyde edema and interstitial edema. The effectiveness of the anti-inflammatory effect of the flavonoid fraction of the herb crowned serpentine in vitro experiments was assessed by the rate of the enzymatic reaction catalyzed by inducible NO synthase. The activity of the iNOS enzyme in experiments was assessed by the rate of the reaction catalyzed by iNOS in vitro at 37 C. The study of the capillary-strengthening effect of the flavonoid fraction of the herb Serpucha crowned was carried out according to the "Method for determining the reactivity of skin capillaries to inflammatory stimuli" on a model of local in-flammatory reaction (xylene inflammation) in rats. Results. When studying the acute toxicity of the flavonoid fraction of the herb Serpucha crown, LD50 values were not established, since doses of the studied extract administered into the stomach of mice did not cause death of the animals. In accordance with the classification of toxicity of chemical substances according to GOST 12.1.007-76 "Harmful substances. Classification and general safety requirements", the flavonoid fraction of the herb crowned Serpucha is a low-hazard substance. As a result of the analysis of the data obtained, it was established that the flavonoid fraction of the herb serpukha crowned in doses of 100 and 200 mg/kg has an anti-inflammatory effect, significantly reducing formaldehyde edema in animals by 18 and 20%, respectively, compared with the control group of animals. It was established that the flavonoid fraction of the herb Serpucha crowned at a dose of 200 mg/kg has a pronounced anti-exudative effect, significantly reducing interstitial edema in animals by 22% compared to the control group of an-imals. In vitro experiments, the flavonoid fraction of the herb Serpucha crown inhibits the rate of the iNOS reaction by 1.5 times compared to the con-trol, which indicates the presence of pronounced anti-inflammatory activity of this sample. The studied fraction has a pronounced capillary-strengthening effect under the conditions of an experimental model of xylene inflammation, reducing the permeability of the vascular wall. Conclusions. The results of the studies indicate that the flavonoid fraction of the herb Serpucha crown, in terms of acute toxicity, belongs to the cat-egory of low-hazard substances and has a pronounced anti-inflammatory and capillary-strengthening effect.

Eucalypt Extracts Prepared by a No-Waste Method and Their 3D-Printed Dosage Forms Show Antimicrobial and Anti-Inflammatory Activity.

The pharmaceutical industry usually utilizes either hydrophobic or hydrophilic substances extracted from raw plant materials to prepare a final product. However, the waste products from the plant material still contain biologically active components with the opposite solubility. The aim of this study was to enhance the comprehensive usability of plant materials by developing a new no-waste extraction method for eucalypt leaves and by investigating the phytochemical and pharmacological properties of eucalypt extracts and their 3D-printed dosage forms. The present extraction method enabled us to prepare both hydrophobic soft extracts and hydrophilic (aqueous) dry extracts. We identified a total of 28 terpenes in the hydrophobic soft extract. In the hydrophilic dry extract, a total of 57 substances were identified, and 26 of them were successfully isolated. The eucalypt extracts studied showed significant antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans, Corynebacterium diphtheriae gravis, and Corynebacterium diphtheriae mitis. The anti-inflammatory activity of the dry extract was studied using a formalin-induced-edema model in mice. The maximum anti-exudative effect of the dry extract was 61.5% at a dose of 20 mg/kg. Composite gels of polyethylene oxide (PEO) and eucalypt extract were developed, and the key process parameters for semi-solid extrusion (SSE) 3D printing of such gels were verified. The SSE 3D-printed preparations of novel synergistically acting eucalypt extracts could have uses in antimicrobial and anti-inflammatory medicinal applications.

Micronutrients Role in the Proinflammatory Cytokine Gene Expression Regulation in COVID-19 and Post-COVID-19 Syndromes

A number of micronutrients in the diet are substances capable of inhibiting the genes expression of cyclooxygenases COX-1 and COX-2 and inducible NO synthase that are markers of the inflammatory process in COVID-19. The study aims at the development of the composition micronutrients – an inhibitor of hyperinflammatory reaction as an effective component of personalized nutrition in COVID and post-COVID syndromes. The thesis presents the anti-inflammatory potential of some micronutrients; proves the impact of flavonoids, ascorbic acid, glycyrrhizic acid and zinc on different targets; describes developed two-, three- and four-component compositions of the listed micronutrients in different ratios, which will ensure effectiveness against a larger number of targets. For preclinical studies of anti-inflammatory activity, a man selected six composition samples with maximum values of antioxidant activity using regression analysis; determined the biological activity of the composition samples: in vitro – using specific enzyme biotest systems based on inducible NO synthase and appropriate software, in vivo – on a model of acute aseptic and chronic inflammation in 220 outbred male Wistar rats. In vitro experiment confirms that the anti-inflammatory activity of experimental samples of the micronutrients composition decreases in the following series: III-2 > III-1 > VI-2 > VI-1 > I. The blood plasma analysis of rats in vivo proves that with prolonged course use, micronutrients composition samples III-1, III-2, VI-1 and VI-2 exhibit a pronounced antiexudative effect and lead to a significant decrease in COX-2. The course micronutrients composition introduction at a dose of 25 mg/kg leads to a significant decrease in the COX-2 concentration in all the studied animal groups. There is the COX-2 activity suppression in sample III-2 to a greater extent. The authors recommend the three-component composition including a micronized purified flavonoid fraction of sea buckthorn meal, glycyrrhizic and ascorbic acids in a ratio of 30:10:100 as a biologically active food additive in the diet of personalized nutrition for COVID and post-COVID syndromes.

STAGES OF PRECLINICAL STUDIES OF HERBS EXTRACTS OF ARTEMISIA SPECIES

At the present stage of the development of science, it remains relevant to create new medicines of plant origin with the use of extracts as active substances and improvement of the composition and technology of existing ones.
 The article aimed to highlight the main stages of preclinical studies of herbal extracts of Artemisia species to establish their pharmacological activity, preclinical safety profile, and prospects for further research in developing a medicinal product.
 As a result of the research conducted using the method of generalization and systematic analysis, we identified the main stages of pharmacological research of plant extracts as medicinal substances using the example of Artemisia absinthium L. and Artemisia vulgaris L. extracts.
 Identifying the main stages of pharmacological research of plant extracts is necessary to establish the preclinical profile of the substance's safety, pharmacological effectiveness, and prospects for further study in the development of the medicinal product.
 In the first stage, a toxico-pharmacological study of the extracts is carried out, which includes the study of acute toxicity of the еxtracts. It was established that the intragastric administration of extracts of Artemisia absinthium L. and Artemisia vulgaris L. at a dose of 6000 mg/kg does not lead to the death of animals, which indicates the absence of toxic effects of the extracts in this dose, and characterizes them as practically non-toxic (toxicity class V, LD50 > 5000 mg/kg).
 At the second stage of pharmacological research, the anti-inflammatory activity of Artemisia absinthium L. and Artemisia vulgaris L. extracts was studied (on models of formalin, carrageenan, and zymosan edema). It was established that the sections of Artemisia absinthium L. and Artemisia vulgaris L. showed a pronounced anti-exudative effect throughout the experiment.
 At the third research stage, a study of specific pharmacological activity – hepatoprotective (antioxidant) training was activity.
 It was found that extracts of Artemisia species exhibit hepatoprotective activity in acute toxic liver damage, which leads to a decrease in the intensity of the lipid peroxidation process and a reduction in the harmful effect of tetrachloromethane, bringing the biochemical indicators of blood and liver homogenate of animals to the level of intact animals. The results of the research show that the extract of the herb Artemisia absinthium L. at a dose of 25 mg/kg of the animal's body weight showed a more intense and more effective effect in acute hepatitis compared to the extract of the herb Artemisia vulgaris L. The extract of the herb Artemisia absinthium L. are not inferior to the hepatoprotective effect of the comparative drug "Silibor".
 So, we established a general design of pharmacological research, which included the following stages:
 I stage. Study of the harmlessness of extracts - study of acute toxicity.
 II stage. Study of pharmacological activity of extracts - anti-inflammatory activity.
 III stage. Research of specific pharmacological activity – hepatoprotective (antioxidative) activity.
 Thus, a properly planned preclinical study showed the absence of toxic effects of Artemisia absinthium L. and Artemisia vulgaris L. extracts and the prospect of further pharmacological experiments.

СИНТЕЗ ТА АНТИЕКСУДАТИВНА АКТИВНІСТЬ N-ОКСИДІВ 4-ПІРИДИНІЛОКСИЗАМІЩЕНИХ (БЕНЗ)ІМІДАЗО[2,1-b][1,3]ТІАЗИНІВ

The imidazo[2,1-b][1,3]thiazine nucleus, as well as the pyridine-N-oxide fragment, are pharmacophore groups that have received much attention from researchers. That is why the combination of these scaffolds in the structure of a single molecule seems to be quite attractive from chemical and biological point of view. Synthetically available 4-pyridinyloxy-substituted (benzo)imidazo[2,1-b]thiazines were used as precursors to obtain previously unknown (benzo)imidazo[2,1-b][1,3]thiazin-6-yloxypyridine 1-oxides. It was found that the oxidation of the latter with m-chlorobenzoic acid under mild reaction conditions using dichloromethane as a solvent at room temperature proceeds smoothly and selectively to obtain only the target products. The composition and structure of the synthesized pyridine-N-oxides are unambiguously confirmed by complex physicochemical analysis, particularly by 1H and 13C NMR spectroscopy, chromato-mass spectrometry, as well as elemental analysis data. The antiexudative activity of (benz)imidazo[2,1-b][1,3]thiazin-6-yloxypyridine 1-oxides was studied in vivo in a model of carrageenan-induced paw edema in white outbred male rats. The development of edema was considered from increasing the volume of the paw 4 hours after the introduction of carrageenan. Quantitative assessment of antiexudative activity was performed by the degree of reduction of rat paw edema, and the rate of suppression of the inflammatory process was calculated. Performed bioscreening showed that the synthesized pyridine-N-oxides are characterized by weak anti-inflammatory activity, and only 2-chloro-4-[(2,3-diphenyl-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-6-yl)oxy]pyridine 1-oxide 2a has moderate antiexudative effect with of inflammatory inhibition rate of 31.9%. This compound is thus of interest for further structural modification in order to obtain potential non-steroidal anti-inflammatory agents. It is important to note that the presence in the structure of the synthesized derivatives 2a-e of N-oxide fragment is very promising for the design of anti-inflammatory agents, which are characterized by the absence of side effects caused by inhibition of cyclooxygenase-1.

Effect of phytoneering remedy BNO 2103 on the course of experimental exudative inflammation caused by different phlogogens

Kidney and urinary tract diseases play an important role in the disease distribution in most countries of the world. The pharmaceutical industry offers many means for the treatment and prevention of these diseases, but there is a trending tendency to pay more attention to herbal medicines, their empirical application and scientific study. The aim of this research is to study anti-inflammatory properties of standardized herbal composition BNO 2103 in a model of paw inflammation in rats caused by different phlogogens to justify the use of it in the treatment of chronic kidney disease (CKD). Materials and methods. The experimental study was performed using 90 male white outbreed rats weighing 150–200 g, which were divided into 3 series of 30 animals each, each series included 3 groups. Inflammation of the paw was induced by subplantar administration of phlogogens – zymosan, histamine and serotonin. The study agent and the reference drug, diclofenac sodium, were administered intragastrically (i. g.) once. Edema was observed and recorded, and anti-inflammatory activity (AIA) was assessed in 0.5, 1.0, 2.0, 3.0 and 6.0 hours after phlogogen injection. Results. BNO 2103 showed a remarkable anti-exudative effect in the model of zymosan and histamine edema, being significantly superior to diclofenac sodium. In the serotonin edema model, BNO 2103 was significantly superior to the comparator by the endpoints, showing the moderate but prolonged anti-exudative effect. Conclusions. BNO 2103 has the significant anti-inflammatory effect, exerting an inhibitory effect on exudative inflammation caused by various phlogogens (zymosan, histamine, serotonin), mainly acting on the lipoxygenase pathway of arachidonic acid conversion, which is most likely due to the presence of flavonoids. This allows us to consider BNO 2103 as a promising drug for the treatment of CKD.

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

Characteristics of the mechanisms of anti-inflammatory action of cryopreserved placenta extract and diclofenac sodium by their threaded administration

Introduction. Inflammation is a complex multicomponent adaptive pathological process based on three enzymatic pathways of arachidonic acid metabolism: cyclooxygenase, lipoxygenase and epoxygenase. Nonsteroidal anti-inflammatory drugs are the most numerous and most widely used group of drugs used in the pharmacocorrection of inflammatory processes of various etiologies.
 Purpose of the study. The aim is to characterize the effect of cryopreserved placenta extract on the anti-inflammatory activity of diclofenac sodium with their threaded administration in a model of zymosan-induced inflammation.
 Materials and methods. In vivo experimental studies were performed on 28 nonlinear laboratory male rats weighing 200–220 g. Acute exudative inflammation was reproduced by subplantar administration of rat limb 0,1 ml of 2,0% zymosan suspension. The anti-exudative effect was assessed by the magnitude of limb edema, which was assessed using an aqueous plethysmometer.
 Results and discussion. The study showed that subplantar administration of 2,0% suspension of zymosan led to a statistically significant (p < 0,05) increase in the volume of the damaged limb after 30 minutes. by 28,1 ± 5,4% relative to baseline and was 2,01 ± 0,06 ml. The most pronounced and almost comparable anti-inflammatory activity was observed against the background of the use of cryopreserved placenta extract and the combined use of diclofenac sodium and cryopreserved placenta extract. Thus, for 60 min the antiinflammatory activity was (p < 0,05) 46,5% and 53,2%, respectively.
 Conclusions. It is established that one of the leading mechanisms of anti-inflammatory activity of cryopreserved placenta extract is the inhibition of the lipoxygenase pathway of arachidonic acid metabolism. This was indicated by statistically significant (p < 0,05) suppression of zymosaninduced inflammation in rats by 78,8% and 74,8% by 120 and 180 min, respectively.

An Experimental Study of the Cryopreserved Placenta Extract Effect On the Sodium Diclofenac Anti-Inflammatory Activity

Background. As a means of correcting the ulcerogenic effect of nonsteroidal anti-inflammatory drugs, our attention was attracted by a cryopreserved extract of the human placenta, which has a multivector spectrum of biological activity. To date, there is no information about its effect on the specific activity of this class of medicines (anti-inflammatory, analgesic, etc.) in published sources. Objective. We are aimed to characterize the effect of cryopreserved placenta extract on the anti-inflammatory activity of diclofenac sodium when administered separately in a model of acute exudative inflammation. Methods. Experimental studies in vivo were conducted on 28 nonlinear male laboratory rats. The model of acute exudative inflammation was reproduced by subplantar injection of 0.1 ml of 1.0% aqueous solution of λ-karagenin into the right hind limb of rats. Cryopreserved placenta extract was administered intramuscularly at a dose of 0.16 ml/kg 60 minutes before diclofenac sodium (8 mg/kg). Results. Preventive administration of diclofenac sodium caused an antiexudative effect as early as 30 minutes after administration of λ-karagenin – its anti-inflammatory activity was 11.0%, which is 4.6 times higher than similar indicators at the same time in rats injected with placental cryoextract. At 60 minutes of observation, diclofenac sodium was comparable in anti-inflammatory activity with cryopreserved placenta extract: 28.6% and 22.2%, respectively, but at 120 and 180 minutes, diclofenac sodium exceeded the studied cryoextract in antiphlogistic effect by 1.6 times in both periods of observation. The anti-inflammatory effect of the combined separate administration of placenta cryoextract and diclofenac sodium before λ-karagenin for 30 and 60 minutes was 12.7% and 32.3%, respectively, which is comparable with analogous indicators against the background of diclofenac sodium monotherapy. However, at 120 minutes of observation, the group of combined use of placenta cryoextract and diclofenac sodium showed the greatest anti-inflammatory effect among rats of all the studied groups – 52.6%, which was 2.2 times higher than the indicators of the placenta cryoextract monotherapy group and 1.4 times lower than the indicators of the rats of the diclofenac sodium monotherapy group. Conclusions. 4 hours after administration, placental cryoextract had a suppressive effect on kinins like diclofenac sodium, and in the prostaglandin period of caragenin-induced inflammation against the background of combined use of the studied cryoextract and diclofenac sodium, the anti-inflammatory activity was 46.4 %. This suggests a suppressive effect on the production of prostaglandins as a possible mechanism of anti-exudative action of cryopreserved placenta extract.

COMPARATIVE STUDY OF ANTI-INFLAMMATORY, ANALGESIC AND ANTI-ULCER EFFECT OF CANCARIUS MUSHROOM EXTRACT (CANTHARELLUS CIBARIUS) AND SHIITAKE MUSHROOM EXTRACT (LENTINUS EDODES) IN THE EXPERIMENT

Mushrooms are appreciated not only for their nutritional value and bioavailability, but also for their medicinal properties. There are a growing number of the studies focused on investigating medical preparation base on natural compounds, including those isolated from a number of fungi species of fungi species. The aim of this study is to compare anti-inflammatory, analgesic and antiulcer effects of extracts of shiitake mushrooms and chanterelle mushrooms in an experiment on rats. Materials and methods. The experiment involved 30 white female rats weighing 170-210 g., divided into 5 groups: group 1 included intact animals; group 2 included animals with modelled pathology; group 3 included animals, which received chanterelle extract; group 4 involved animals, which received shiitake mushroom extract, and group-5 rats received the reference drug. Observation of changes over the inflammatory process in the model of carrageenan-induced inflammation in the paw of the rats revealed an anti-exudative effect of varying intensity that made up 36.84% for the of chanterelle mushroom extract and 15.79% for shiitake mushroom extract. The dynamics of trypsin-induced inflammatory process showed moderate anti-inflammatory activity, 32.02%, during the courses of the therapy with chanterelle mushroom extract. According to the indicator of analgesic effects produced by the studied extracts, the highest indicator was reached by the chanterelle mushroom extract (33.53%) that exceeded the analgesic effect of the shiitake mushroom extract (17.65%). Therapeutic and prophylactic administration of the chanterelle mushroom extract in a dose of 10 mg / kg in the model of aspirin-induced gastric ulcer in rats showed a pronounced anti-ulcer effect which made up 66.7% compared with that by shiitake mushroom extract (33.4%) and the reference drug “Altan” (100%). Conclusion. The obtained data have demonstrated the promise of using the extracts of chanterelle and shiitake mushrooms for the therapeutic and prophylactic purposes.

Ability of Mexidol to Enhance Antiexudative Effect of Diclofenac Sodium and Etoricoxib in Rats and Mice with Carrageenan-Induced Edema

Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most widely used drugs in existence. However, they can cause numerous side effects. Therefore, it is crucial to develop approaches to reducing the severity of their side effects. The purpose of this study is to investigate the effect of mexidol on the anti-inflammatory activity of NSAIDs, such as selective cyclooxygenase (COX)-2 inhibitor etoricoxib and nonselective COX inhibitor diclofenac sodium. Effect of a single oral dose of the drugs was evaluated in rats and mice with carrageenan-induced edema by measuring the severity of edema over a period of 4 and 6 h, respectively. Diclofenac sodium at doses of 1 and 10 mg/kg exhibits a dose-dependent antiexudative effect, the effect of etoricoxib at these doses is comparable, and mexidol at a dose of 25 mg/kg does not exhibit an antiexudative effect. In mice, the effect of a combination of diclofenac sodium at a dose of 1 mg/kg and mexidol at a dose of 25 mg/kg is noninferior to diclofenac sodium at a dose of 10 mg/kg and superior to the effect of diclofenac sodium at a dose of 1 mg/kg. In rats, the combination of diclofenac sodium and mexidol significantly reduces the severity of edema at 4 h after its induction compared with diclofenac sodium at a dose of 1 mg/kg only. In mice, a combination of etoricoxib at a dose of 1 mg/kg and mexidol at a dose of 25 mg/kg is more effective than etoricoxib at doses of 1 and 10 mg/kg. In rats, etoricoxib at a dose of 10 mg/kg and the combination of etoricoxib at a dose of 1 mg/kg and mexidol at a dose of 25 mg/kg have a comparable effect. Mexidol at a low dose (25 mg/kg) enhances the antiexudative effect of diclofenac sodium and etoricoxib. Therefore, a decrease in the dose of NSAIDs in combination with mexidol will help to reduce the side effects of these drugs.

Investigation of anti-inflammatory and antipyretic activity of polymorphic modification of n-(trifluoromethylphenyl)-4-hydroxy-2,2-dioxo-1h-2λ6,1-benzothiazine-3-carboxamide derivative in rats

Annotation. Polymorphism among biologically active substances is an extremely important factor that modifies the therapeutic properties of pharmaceutical substances and dosage forms, significantly affects the parameters of their biological activity and pharmacokinetics. Chemical synthesis among the derivatives of 4-R-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acids gave the leader compound N-(4-trifluoromethylphenyl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide, the crystalline polymorph of which in the form of plates has a pronounced analgesic activity. The aim of the study was to investigate the anti-inflammatory activity of compound B by its effect on various components of the inflammatory reaction, as well as the antipyretic effect of this compound in rats. The anti-alterative activity was determined on the model of planar skin wounds, the antiproliferative effect - on the model of cotton granuloma, the anti-exudative effect - on the model of toxic pulmonary edema in rats. The antipyretic effect was studied in a model of milk fever in rats. The study was performed on 91 white male Wistar rats. Statistical processing of the obtained results was performed using the program "STATISTICA 6.1" by methods of variation statistics using parametric and nonparametric methods. The results showed that the polymorphic compound B has anti-inflammatory activity on all components of the inflammatory reaction - alteration, exudation and proliferation. In terms of efficacy in the model of experimental inflammation, this substance is superior to meloxicam, as its ED50 when administered orally is 5.2 mg/kg, while the reference drug - 9.1 mg/kg. Compound B exhibits a pronounced antipyretic effect in a rat fever model. Therefore, the polymorphic modification of the carboxamide derivative in the form of plates is promising for further research in order to create on its basis a drug with analgesic, anti-inflammatory and antipyretic properties.

Influence of the potential dependent calcium channel blockers to the development of carrageenan-induced aseptic inflammation

Background: A number of patients with diseases of the cardiovascular system simultaneously take anti-inflammatory medicines due to the presence of concomitant chronic inflammatory diseases such as rheumatism, arthritis, and podagra. Considering the above, it seems important to study the effect of calcium antagonists (CA) on the course of the inflammatory process. Aim and Objectives: The purpose of the study was an investigation of the effect of amlodipine, diltiazem, and cinnarizine in comparison with diclofenac sodium on the course of carrageenan-induced aseptic arthritis. Materials and Methods: The experiments were carried out on outbred white rats, males, and weigh 150–170 g. The inflammation was induced by the subplantary injection of a 1% aqueous solution of carrageenan in a volume of 0.1 ml. The studied medicines diclofenac sodium at a dose of 10 mg/kg, amlodipine and diltiazem at doses of 20 mg/kg, and cinnarizine at doses of 50 mg/kg were intragastrically administered to experimental animals 1 h before the injection of carrageenan. Measurement of the paw volume of animals was carried out using a plethysmometer Results: The anti-inflammatory activity of amlodipine in the indicated hours of observation was 34.1, 36.8, 37.8, and 39.7%, respectively. Сinnarizine also had a distinct anti-exudative effect, after 1, 2, 3, and 4 h of the experiment value of anti-inflammatory activity of it were as following: 38.6, 40.3, 41.9, and 44.0%, respectively. Conclusion: Blockers of potential-dependent calcium channels clearly suppress the exudative phase of aseptic inflammation. The studied medicines are arranged in a descending order by their pharmacological activity in the following row: diclofenac sodium = diltiazem> cinnarizine> amlodipine.

Experimental substantiation of anti-inflammatory activity of a gel containing Convolvulus arvensis extract in carrageenan-induced aseptic arthritis

Background: Despite the huge number of drugs used for the treatment of inflammatory diseases, the modern assortment of this group of drugs does not solve the problem of their successful therapy and relapses, the frequency of which after stopping the administration can reach high values. Aim and Objective: The aim of this work was to study the anti-inflammatory activity of a gel containing Convolvulus arvensis in aseptic arthritis induced by carrageenan. Materials and Methods: Experimental studies were carried out on sexually mature white males’ rats with an initial weight of 155–180 g. A 5% C. arvensis extract containing gel and 5% ibuprofen gel was applied to the surface of the right hind paw of the animals 1 h before the injection of flogogen and after each measurement of the paw volume. Measurement of the paw volume of animals was carried out using a plethysmometer Results: A more expressed antiexudative effect was observed when used C. arvensis extract-containing gel. Hence, after 1, 2.3, and 4 h from the beginning of the action of carrageenan, the volume of the rat paws increased compared to the initial by 45.5; 51.9; 59.7; and 51.9%, respectively. An almost twofold inhibition of the development of the exudation process was observed under the influence of C. arvensis extract containing gel in comparison with the control group. Conclusions: The gel containing the extract of C. arvensis has an expressed antiexudative effect in aseptic arthritis induced by carrageenan. In terms of its antiexudative activity, the preparation containing the extract of C. arvensis is not inferior to ibuprofen when applied locally in the form of a gel.

PHARMACOLOGICAL STUDIES OF THE DENTAL GEL OF COMBINED COMPOSITION

The growing prevalence of periodontal and oral mucosa diseases results in increasing number of people in need of orthopedic treatment due to tooth loss, which, accordingly, requires quality dental care.
 The aim – is to study the pharmacological action of a new dental drug of combined composition in the form of a mucoadhesive gel under the conditional name "Cholident" for the treatment and prevention of inflammatory diseases of the periodontium, oral mucosa and to facilitate adaptation to removable dentures.
 Material and Methods. The study of antiexudative activity of the dental gel was performed on a model of carrageenan edema using electronic plethysmometer, manufactured by WPI. As a reference drug, "Kamistad®" gel (STADA Arzneimittel, AG, Germany) was used. Evaluation of the reparative effect of the gel was performed on the model of thermal burn. At light optical research of histologic micronutrients epithelialization, border zone creation, infiltration of inflammatory cells (macrophages) and angiogenesis have been evaluated.
 Results. After application of the gel under study, the antiexudative effect began to appear after 30 minutes, as evidenced by a decrease in the volume of the affected paw, while a similar effect of the comparison drug was observed only 60 minutes after application to the paw. The study drug also showed a longer action, as the antiexudative effect was still observed 120 min after application, while in the control group there was no decrease in paw volume after 90 min of the experiment. Sustained decrease of the combustion wound area in the animals to which the studied gel was applied has been demonstrated. Activation of epithelial proliferation in the border area, increase in the height of regenerating epidermis and formation of a thin layer of cells in the combustion area, signs of demarcation zone formation, and increase in density of newly formed vessels in the border zone dermis have been revealed by the results of histological examination.
 Conclusions. The results show that the studied gel has a moderate anti-inflammatory effect, which in severity and duration of action exceeds the comparison drug, reduces the local inflammatory response and promotes skin regeneration in the acute phase of combustion.

Comparative pharmacognostic and pharmacological study of Salvia verticillata and Salvia officinalis leaves to establish the prospect of creating a new medicines

The raw material base of medicinal plants in Ukraine is sufficient only for half of the pharmacopoeial species. Most of them are growing in insufficient quantities and there is a need to import them. In the conditions of import dependence and scarcity of domestic raw materials, the search for new sources of biologically active substances among the representatives of the Ukrainian flora is an urgent aim of modern pharmaceutical science. The purpose of the research is to conduct comparative pharmacognostic and pharmacological studies of S. verticillata and S. officinalis leaves to determine the possibility of using non-pharmacopoeial species in pharmaceutical and medical practice. Materials and methods. The objects of the study are S. verticillata and S. officinalis leaves, which was harvested in the botanical garden of the I. Franko Lviv National University. The morphological and anatomical structure of the species leaves was studied by light microscopy. The study of macro- and microelement composition in the S. officinalis and S. verticillata leaves was carried out by atomic emission spectrographic method. Determination of the qualitative composition and quantitative content of the main groups of biologically active substances was carried out by HPLC. The quantitative determination of phenolic compounds was also carried out by spectrophotometric method. The anti-inflammatory activity of galenic extracts from the leaves of the studied species was studied using a model of acute inflammatory edema caused by subplant implantation of a carrageenin solution. Results. Using light microscopy, we studied the key microscopic and diagnostic signs of S. verticillata leaves. The content of 15 micro and macroelements was found in both studied species. 15 and 14 amino acids, 8 and 6 saponins, respectively, were identified in the S. officinalis and S. verticillata leaves. By HPLC, the qualitative composition and quantitative content of phenolic substances in the S. officinalis and S. verticillata leaves (13 and 12 compounds, respectively) was established. The maximum antiexudative effect of the dry extracts from the S officinalis and S. verticillata leaves was observed at a dose of 50 mg/kg. The dominant of elements are silicon, phosphorus, magnesium, calcium, sodium and potassium. The total content of trace elements in the leaves of S. verticillata is 1.78 times higher than in the pharmacopeia S. officinalis . The total content of saponins predominates in the leaves of S. verticillata and is 15.09 mg/g, which is 12.1 % more than in the pharmacopeia specie. The total flavonoid content in the leaves of S. verticillata is 1.57 times higher than in the pharmacopeia one S. officinalis , the content of hydroxycinnamic acids is highest in the S. officinalis leaves. The highest total content of all phenolic compounds is characteristic of S. verticillata leaves, which is 37.18 % (1.37 times) more than the pharmacopeia S. officinalis . At a dose of 50 mg/kg the anti-inflammatory effect of the dry extract from the S. verticillata leaves was comparable to the activity of the substance from the S. officinalis leaves. Conclusions. As a result of comparative pharmacognostic and pharmacological study of S. verticillata and S. officinalis leaves, it was found that S. verticillata is a promising species for introduction into medical and pharmaceutical practice, precisely as a source of phenolic compounds. The anti-inflammatory effect of the dry extract of S. verticillata leaves was compared with that of the substance of S. officinalis leaves, which indicates the possibility of creating a new anti-inflammatory medicine based on it.

The comparative study of the anti-inflammatory action of “Аrthritan” and the phytocomposition on its basis

According to the WHO expert estimates, 75 % of patients can be cured with the help of herbal remedies. Therefore, the future of modern medicine and pharmacy is associated with the integration of the evidence-based and natural medicine. The drug “Arthritan” manufactured by LLC “Zemna Green Planet” based on extracts of the medicinal plant raw material – willow bark, Echinacea flowers, birch leaves, elderberry flowers – is a promising drug for rheumatic diseases and potentially has the anti-inflammatory, analgesic, chondroprotective effects.Aim. To study the anti-inflammatory properties of “Arthritan” and the phytocomposition based on it in order to substantiate its use in clinical practice as an anti-inflammatory, analgesic and chondroprotective agent.Materials and methods. The anti-inflammatory effect of “Arthritan” and the phytocomposition based on it was studied on 50 white non-linear rats of both sexes using the carrageenan inflammation model.Results. On the model of exudative inflammation of the extremities in rats the drugs “Arthritan”, “Nephrolik” and the phytocomposition exhibit a moderate level of the anti-inflammatory effect, which is the most pronounced when using the phytocomposition and reaches 29.2 %. Under the effect of “Nevrin” the anti-inflammatory action is statistically insignificant or weakly expressed and reaches the maximum of 14.7 %, which does not have pharmacological significance since the level of the pharmacological activity of at least 20 % is significant for the experimental study of anti-inflammatory and / or analgesic agents. This allows us to conclude that the basis of the relatively high anti-inflammatory activity of the phytocomposition is the summation of the pharmacological effects of “Arthritan” and “Nephrolik”, and the contribution to the final level of activity of the research combination of “Nevrin” is insignificant.Conclusions. In the course of studying the anti-inflammatory properties of the drugs under research on the model carrageenin inflammation of the rat’s foot the anti-exudative effect of various severity was found, which amounted to 19.8 % for “Arthritan”, for “Nevrin” – 14.7 %, “Nephrolik” – 21.0 % and their combinations – 29.2 %. By the level of its anti-inflammatory activity the phytocomposition studied significantly exceeds the activity of its components. It is based on the summation of the pharmacological effects of “Arthritan” and “Nephrolik”, while the contribution to the final level of activity of “Nevrin” is insignificant.

Антиексудативні властивості рідкого спиртово-водного екстракту листя аїру звичайного (Acorus calamus L.)

Мета дослідження – вивчення антиексудативних властивостей рідкого спиртово-водного екстракту листя аїру звичайного (Acorus calamus L.) (РСВЕЛА). РСВЕЛА був отриманий на кафедрі ботаніки НФаУ під керівництвом професора Т. М. Гонтової. Протизапальні властивості РСВЕЛА досліджені на білих безпородних щурах на моделях карагенінового та гістамінових набряків. Досліджуваний РСВЕЛА (0,5 мл / кг) і препарати порівняння, а саме: диклофенак натрію (у дозі 8 мг / кг), кверцетин (у дозі 11 мг / кг) і лоратадин (у дозі 1 мг / кг), на моделі карагенінового та гістаміновими набряків застосовували в лікувально-профілактичному режимі: внутрішньошлунково одноразово щодня протягом 5 діб до моделювання запалення й за 1 год до ін'єкції флогогену (карагеніну або гістаміну відповідно). Розвиток набряку спостерігали в динаміці за показником об'єму лапи, який визначали за допомогою цифрового плетизмометра. Через 24 год після введення флогогену в тварин визначали кількість лейкоцитів і ШОЕ. Встановлено, що на моделі карагенінового та гістамінового набряку РСВЕЛА чинить протинабрякову дію. Антиексудативна активність РСВЕЛА склала 68,9 % (р < 0,05) на 120 хв запалення та 79,5 % (р < 0,05) на 180 хв у разі карагенінового набряку. На моделі гістамінового набряку антиексудативна дія РСВЕЛА склала 50,8; 27,7 і 50,0 % відповідно на 30, 60 і 90 хв набряку. За виразністю антиексудативної дії, ступенем зниження ШОЕ та показника лейкоцитозу РСВЕЛА не поступається всім трьом препаратам порівняння: диклофенаку натрію, кверцетину і лоратадину. Таким чином, встановлено, що РСВЕЛА має антиексудативну дію, що є обгрунтуванням подальших досліджень з перспективою створення на його основі нових ефективних фітопрепаратів для профілактики та фармакокорекції запальних процесів.

Anti-inflammatory activity of a combined gel based on plant components in a model of adjuvant arthritis in rats

Topicality. According to WHO, more than 4 % of the population globe suffer from a variety of joint and spine disorders. In Ukraine, more than 34,500 patients with primary joint diseases are registered annually. Diseases of the musculoskeletal system have a chronic course that requires long-term treatment and puts increased demands on the effectiveness and safety of anti-inflammatory drugs. Therefore, the above justifies the feasibility and relevance of the search for new highly effective and safe domestic drugs.Aim. To make an experimental study of the pharmacological activity of a combined gel for the treatment of inflammatory joint disease if chronic inflammation – adjuvant arthritis in rats.Materials and methods. The subjects of the study were model samples of a combined gel with active pharmaceutical ingredients - white willow bark, common sage leaves dried extract and methyl salicylate. The anti-inflammatory properties of the new gel were studied using a model of adjuvant arthritis in rats (sensitization to the base of the tail by PAF at 0.1 ml/animal, and the introduction on the seventh day of a resolving dose by PAF 0.1 ml/animal under aponeurosis of the right hind limb subplantarly). Diclofenac sodium gel, 5 %, was used as the comparison drug. The test specimens were applied to the affected paw surface daily at a dose of 0.2 ml/animal. Indicators: volume of edema of animal paws (3, 7, 10, 14 and 21 days of experiment); leukocyte and FAN content in the blood and alkaline and acid phosphatase activity and serum CIK content (21 days).Results and discussion. According to the results of studies, against the background of chronic inflammation, the combined gel shows an efficiency comparing to the diclofenac sodium gel, 5 %, conceding to it only in its anti-exudative effect. However, a positive feature of the new gel, in contrast to the drug of comparison, is the ability to maintain the cellular level of non-specific animal immunity, which is significantly impaired under the condition of this pathology.Conclusions. The obtained experimental data substantiate the prospect of further pharmacological studies of the developed combination gel based on the active ingredients of white willow bark, sage medicinal leaves dried extract and methyl salicylate.

Натурные испытания биологически активной добавки «Ивлаксин» у больных с острыми воспалительными заболеваниями

Clinical tests were carried out in the representative group of patients with focal left-sided pneumonia (5 men and 7 women aged 18–41). Special-use product was included in in-patient department patients’ diet: 2 tablets in the first intake, then 1 tablet 4 times a day. Course of treatment was 21 days. Biologically active dietary supplement was prescribed together with general therapeutic treatment according to generally accepted standards of care. Control group included 15 patients randomized depending on sex and age who took only medicine. The author measured body temperature, studied the results of general blood tests, determined the level of C-reactive protein and seromucoids, performed R-graphy of lungs, electrocardiogram before and after treatment, analyzed clinical symptoms (cough, type of expectoration, shortness of breath). Composition of the special-use product was scientifically justified taking pharmacological characteristics of its ingredients and their active agents into account. Introduction of the biologically active dietary supplement in addition to the prescribed therapeutic treatment gave positive effect in relation to the inflammatory process: the patients could easier clear their throats from expectoration, coughed less frequently, and had less intense shortness of breath. It was evident that symptoms of disease recrudescence decreased. It appeared in the decreased intensity and length of fever. In case of acute respiratory viral infection the biologically active dietary supplement had antipyretic activity due to the anti-exudative effect of its ingredients. The author determined the anti-inflammatory effect and reduction of acute intoxication symptoms taking the results of general blood analysis into account. Patients who took special-use product had lower values of an inflammatory process marker – seromucoids. Tissues restored easily. The tested product has anti-inflammatory, antipyretic and analgesic properties. It can be used in complex treatment of acute inflammatory diseases and recrudescence of chronic inflammatory processes.