Enisamium Iodide Research Articles

Study of the degradation behavior of enisamium iodide, tilorone dihydrochloride, morpholinium thiazotate in the soil by the GC-Fid method

The aim. To study the behaviour of enisamium iodide, thiloron dihydrochloride, morpholinium thiazotate, and the suitability of the previously developed GC-FID methodology in soil. Materials and methods. The determination of the Enisamium iodide, Tilorone dihydrochloride, and Morpholinium thiazotate in soil gas chromatography with a flame ionization detector using the Rxi-5 ms (30 m long, 0.25 mm outer diameter and 0.25 μm liquid stationary phase thickness). Results. A study was conducted on the behaviour of enisamium iodide, thiloron dihydrochloride, and morpholinium thiazotate in soil, along with the assessment of the suitability of the developed GC-FID methodology for determination in soil. The half-life in soil was investigated, which amounted to 45 days for enisamium iodide, 30 days for thilorone dihydrochloride, and 7 days for morpholinium thiazotate, with corresponding decay rate constants of 0.001 mg/mL, 0.001 mg/mL, and 0.0005 mg/mL, respectively. Conclusions. The previously developed GC-FID methodology is suitable for the determination of enisamium iodide, thilorone dihydrochloride, and morpholinium thiazotate in soil, with necessary analysis conditions established. Under aerobic conditions, the selected pharmaceutical preparations' dispersion rate followed the following decreasing order: enisamium iodide > thilorone dihydrochloride > morpholinium thiazotate in soil

Greening of the method for simultaneous determining the enisamium iodide and tilorone dihydrochloride using GC-FID assay

Pharmaceutical companies in Ukraine aspire to develop their innovative medicinal products and successfully introduce them to the global market. However, along with the prospects of increased usage of these pharmaceuticals, there arises a challenge of heightened waste production, making them a part of the over twenty million tons of PPCPs produced annually. Consequently, one of the tasks in producing new pharmaceuticals is the development of methodologies and approaches not only for quality control but also for their determination in the environment matrices.
 The aim. Develop and validate GC-FID chromatographic method for the simultaneous determination of Enisamium iodide and Tilorone dihydrochloride, evaluate their applicability, and compare their "greenness" with the previously developed HPLC method.
 Materials and methods. The determination of the Tilorone dihydrochloride and Enisamium iodide was carried out by gas chromatography with a flame ionization detector using the Rxi-5 ms (30 m long, 0.25 mm outer diameter and 0.25 μm liquid stationary phase thickness)
 Results. Chromatographic GC-FID methods have been developed for the simultaneous determination of Enisamium iodide and Tilorone dihydrochloride. Optimal sample preparation conditions were established, and a validation process was conducted. A comparison with the previously developed HPLC method was made regarding "greenness."
 Conclusions. The developed GC-FID methodology is accurate and more environmentally friendly compared to the previously established methods. It can be recommended to determine Enisamium iodide and Tilorone dihydrochloride in the environmental matrices. It is considered environmentally friendly based on the overall GREENness (AGREE) scale, scoring 0.73 (>0.70), which demonstrates the environmentally favourable nature of the proposed analytical approach

Окончательные результаты адаптивного рандомизированного открытого контролируемого исследования эффективности и безопасности энисамия йодида в терапии госпитализированных больных с COVID-19

Despite extensive vaccination as well as the introduction of new therapies for COVID-19, morbidity and mortality rates remain high worldwide, especially among the unvaccinated population and patients at risk. One possible strategy for improving the treatment of patients with COVID-19 could be to study the efficacy and safety of existing antiviral or immunomodulatory agents against SARS-CoV-2 and their impact on the course of the disease. Objective. To assess the efficacy and safety of enisamium iodide – Nobazit®, film-coated tablets, 250 mg (Avexima LLC, Russian Federation), for inpatient treatment of moderate coronavirus disease caused by the SARS-CoV-2 (COVID-19). Patients and methods. This was an open-label, multicentre, randomized study that enrolled 304 hospitalized patients with moderate COVID-19. Patients were divided into 2 groups: the enisamium iodide group (n = 151) included patients who received therapy according to the current version of the Interim Guidelines “Prevention, Diagnosis and Treatment of New Coronavirus Infection (COVID-19)” (IG) except for etiotropic drugs in combination with enisamium iodide (500 mg 3 times daily for 7 days); the routine therapy group (n = 153) included patients who received therapy according to IG, including etiotropic drugs. The primary efficacy endpoint (first component) was a composite of the median time (in days) from the initiation of treatment with study drug/routine therapy to sustained resolution of fever, reduction in respiratory rate to less than 22/min, and achievement of blood oxygen saturation (SpO2) more than 96%. The second component of the primary endpoint was the proportion of patients who developed respiratory failure. Secondary endpoints included all-cause mortality, duration of hospitalization, change in World Health Organization (WHO) 8-point scale score, median time to reduction in the severity of major symptoms (fever, cough, headache, myalgia, weakness). Efficacy endpoints were analysed in the intention-to-treat (ITT) and per protocol (PP) populations. Results. As follows from the analysis of the first component of the primary endpoint, the mean number of days from treatment initiation to sustained resolution of fever, normalization of the respiratory rate, and achievement of SpO2 was 8.8 in the enisamium iodide group and 10.6 in the control group (hazard ratio [HR] 0.738, p = 0.013 [97.62% CI: 0.581–0.937]). The proportion of patients who developed respiratory failure in both groups was comparable, indicating that enisamium iodide therapy does not lead to an increased risk of respiratory failure in patients with COVID-19. As for the secondary efficacy endpoints, no statistically significant differences between the groups were shown, except for the WHO 8-point scale score on days 14 and 28 in favour of the study drug (p = 0.024 and p = 0.042, respectively). In addition, there was a trend towards lower mortality in the study drug group than in the control group: 1 and 5 cases, respectively. The addition of enisamium iodide to standard therapy was not associated with a worsening in the treatment safety profile. Conclusion. The statistically significant superiority of the efficacy of adding Nobazit®, film-coated tablets, 250 mg (Avexima LLC, Russian Federation), to routine therapy over routine therapy alone in patients with moderate COVID-19 was proved. Consequently, it is reasonable to recommend the addition of Nobazit® to the standard treatment of patients with COVID-19 of moderate severity. Key words: enisamium iodide, antivirals, etiopathogenetic therapy, SARS-CoV-2, COVID-19, viral-induced lung damage, pneumonia, randomized controlled study, adaptive study, open-label study

To the Calculation of Heat-Exchange Parameters During Drying of Enisamium Iodide

To the Calculation of Heat-Exchange Parameters During Drying of Enisamium Iodide

The mechanisms of anti-inflammatory action of enisamium iodide

The role of cyclooxygenases (COX-1 and/or COX-2), transcription nuclear factor NF-κB, anti-inflammatory cytokines - TGF1b, IL-4, IL-10 and pro-inflammatory cytokines IL-1, IL-6 were studied to substantiate the expediency of antiviral agent enisamium iodide (Nobazit) using to regulate key inflammatory components in acute respiratory infections, IL-8, TNF-alpha in the realization of the pharmacological activity of this drug. Gene expression was determined by real-time RT-PCR, the concentration of interleukins was determined by ELISA, and the viability of peripheral blood mononuclear cells (PBMC) was assessed by the MTT spectrophotometric method. The chemiluminescence method was used to assess PBMC oxidant activity. Enisamium iodide (10 μM) reduced mRNA levels of COX-1, COX-2, NF-κB, TGF1b, IL-1, IL-6 in stimulated PBMC of healthy donors by an average of 48% (p≤0.05). At 5 times higher concentration, 50 μM, enisamium iodide suppressed the expression of these genes by an average of 43% (p≤0.05). At a concentration of 100 μM, enisamium iodide reduced the expression of COX-2, TGF1b, IL-1, IL-6 by an average of 47% (p≤0.05). At a concentration of 10 μM, enisamium iodide stimulated the secretion of IL-10 by mononuclear cells by 1.2 times, p≤0.05. The tested drug at a concentration of 50 μM did not affected on the concentration of IL-1, IL-4, IL-8 and TNF-alpha, but significantly stimulated the production of IL-10 by 1.5 times, p≤0.05. The chemiluminescence method revealed that enisamium iodide in the entire concentration range (10-100 μM) does not reduce the viability of macrophages, but inhibits their oxidative activity (maximum value of CL intensity) by an average of 55% (p≤0.05). The anti-inflammatory effect of enisamium iodide at a concentration of 10 μM may be associated with inhibition of the expression of COX-1, 2, NF-κB, IL-1, IL-6, TGF1b and an increase in the expression and production of IL-10. An additional contribution to the anti-inflammatory activity of enisamium iodide is made by its antioxidant and antiradical activity. The absence of the effect of enisamium iodide (10-100 µM) on the viability of PBMC indicates its safety for the cells of the immune system and the expediency of using it to suppress inflammatory reactions in acute respiratory infections, restore the quality of life of patients and the possibility of using Nobazit as an effective agent for treatment of these infections of various etiologies.

Enisamium Reduces Influenza Virus Shedding and Improves Patient Recovery by Inhibiting Viral RNA Polymerase Activity.

Infections with respiratory viruses constitute a huge burden on our health and economy. Antivirals against some respiratory viruses are available, but further options are urgently needed. Enisamium iodide (laboratory code FAV00A, trade name Amizon) is an antiviral, marketed in countries of the Commonwealth of Independent States for the treatment of viral respiratory infections, but its clinical efficacy and mode of action are not well understood. In this study, we investigated the efficacy of enisamium in patients aged between 18 and 60 years with confirmed influenza virus and other viral respiratory infections. Enisamium treatment resulted in reduced influenza virus shedding (at day 3, 71.2% in the enisamium group tested negative versus 25.0% in placebo group [P < 0.0001]), faster patient recovery (at day 14, 93.9% in the enisamium group had recovered versus 32.5% in placebo group [P < 0.0001]), and reduced disease symptoms (from 9.6 ± 0.7 to 4.6 ± 0.9 score points in enisamium group versus 9.7 ± 1.1 to 5.6 ± 1.1 score points in placebo group [P < 0.0001]) compared to those in the placebo group. Using mass spectrometry, and cell-based and cell-free viral RNA synthesis assays, we identified a hydroxylated metabolite of enisamium, VR17-04. VR17-04 is capable of inhibiting influenza virus RNA synthesis and is present in plasma of patients treated with enisamium. VR17-04 inhibits the activity of the influenza virus RNA polymerase more potently than its parent compound. Overall, these results suggest that enisamium is metabolized in humans to an inhibitor of the influenza virus RNA polymerase that reduces viral shedding and improves patient recovery in influenza patients. (This study has been registered at ClinicalTrials.gov under identifier NCT04682444.).

Предварительные результаты адаптивного рандомизированного открытого контролируемого исследования эффективности и безопасности препарата энисамия йодид для лечения госпитализированных больных с COVID-19

Aim: to assess the efficacy and safety of enisamium iodide (film-coated tablets, 250 mg) for outpatient treatment of moderate-to-severe COVID-19 infection. Patients and Methods: this adaptive, randomized, open-label controlled study on the efficacy and safety of enisamium iodide enrolled 194 patients. The study group included 97 patients, and the comparison group included 97 patients. Comparison group patients received standard therapy. Study group patients received orally 500 mg of enisamium iodide three times daily for seven days. In addition, pathogenic and symptomatic treatment was prescribed. The first component of the primary endpoint was composite efficiency parameter. The second component of the primary endpoint was the proportion of patients with respiratory failure. Registration of deaths, adverse events and serious adverse events was carried out by standard methods. Results: cohort enrollment into part 1 of the study and treatment of all patients were completed. The mean time of the relief of major COVID-19 symptoms (primary combination endpoint) and differences between the study and comparison groups (8 days and 9 days, respectively, p=0.028) were revealed. The rate of respiratory failure in the study group and comparison group was: 4 (4,12%) versus 8 (8,25%) cases respectively. In addition, the effect of this drug on mortality in the groups was compared (one death in the study group and five deaths in the comparison group). The statistical reliability of these differences will be determined during part 2 of this study that started in September 2021. Conclusions: the efficacy and safety of enisamium iodide (film-coated tablets, 250 mg) for the COVID-19 were evaluated. A significant reduction in the time to clinical recovery (by one day) was reported in patients who received enisamium iodide. In addition, the rate of severe respiratory failure and associated mortality also tends to reduce after therapy that includes enisamium iodide. KEYWORDS: enisamium iodide, antivirals, etiopathogenic treatment, SARS-CoV-2, COVID-19, viral lung damage, pneumonia, randomized controlled study, adaptive study, open-label study. FOR CITATION: N.Yu. Pshenichnaya, Zhdanov K.V. Preliminary results of an adaptive randomized open-label controlled study on the efficacy and safety of enisamium iodide for outpatient treatment of the COVID-19 infection. Russian Medical Inquiry. 2021;5(11):705–711 (in Russ.). DOI: 10.32364/2587-6821-2021-5-11-705-711.

Клиническая эффективность препарата Энисамия Йодид в комплексном лечении ОРВИ

The list of etiotropic drugs recommended for the treatment of influenza and other acute respiratory viral infections is not very large and requires sufficient justification for rational tactics of their use. In accordance with the WHO strategy for combating influenza and SARS, it is necessary to continue research to study the clinical efficacy of antiviral drugs with a combined effect - etiotropic, pathogenetic and symptomatic. Enisamium iodide is one of such drugs for etiotropic and pathogenetic therapy of ARVI. Aim. To evaluate the clinical efficacy of the drug enisamium iodide (amizone) in the complex therapy of acute respiratory viral infections (ARVI). Material and methods. The randomized study included 40 patients who were treated during the epidemic season of influenza and ARVI 2019. Patients of the main group received enisamium iodide along with symptomatic therapy, the control group received only symptomatic therapy. The clinical efficacy of treatment was assessed by the duration of the main clinical symptoms of ARVI, the proportion of patients who developed complications requiring antibiotics. Statistical processing of the obtained data was carried out using the SPSS 12.0.2 software for Windows. Results and discussion. The results of a randomized study showed the clinical efficacy and safety of amizone (enisamium iodide) in the complex treatment of acute respiratory viral infections of various etiologies, compared with the use of only symptomatic therapy drugs. The duration of fever and the main clinical symptoms of acute respiratory viral infections were statistically significantly less in the study group than in the control group. Accordingly, the proportion of patients whose body temperature returned to normal on days 2–3 of treatment was statistically significantly higher in the group of patients taking enisamium iodide. Complications requiring antibiotic prescription have been reported only in control patients. Also, the drug was well tolerated and there were no side effects during its use. Conclusions. The results obtained confirmed that enisamium a iodide (amizon) has a good clinical effect in ARVI, reduces the likelihood of complications in patients. The high sensitivity of various respiratory viruses to the drug allows it to be used without etiological decoding of ARVI. Keywords: acute respiratory viral infections (ARVI), influenza, enisamium iodide (amizone), antiviral therapy, clinical efficacy, safety.

Perspectives of treatment of influenza and influenza-like illnesses with Enisamium yodide – Antiviral with anti-inflammatory effect

Background: Enisamium iodide (EI) is a Russian drug whose molecule was developed in the Institute of Pharmacology and Toxicology of Ukraine as an anti-inflammatory and antipyretic agent. Later, other properties of EI were found: inhibition of the influenza virus hemagglutinin, increasing the production of interferon-γ, level of Th1, blood antioxidant activity, inhibition TNF-α and other pro-inflammatory cytokines, activation of macrophages and lysozyme activity. The aim of study was to evaluate the efficacy of antiviral therapy with EI in out-patient patients with influenza and influenza-like illnesses (ILI) without risk factors for severe course of disease. Methods and materials: 124 patients aged 18–55 years with influenza and ILI within 6–48 h of symptoms onset were randomized into 2 groups. 1st group (n = 66) was treated with EI 500 mg tid 5 days, 2nd group (n = 63) received placebo according to the same scheme. In the 1nd group the proportion between influenza and other respiratory viruses was 32.2%: 67.8%, in the 2nd group 31.7%: 68.3%, accordingly. Duration of disease and main clinical symptoms, frequency of complications and speed of the virus elimination from the nasopharynx were estimated. Results: The number of cases with complete recovery within 96 h was 56 (84.8% ± 4.2%) in 1st group and 44 (69.8% ± 5.8%) in 2nd group (p = 0.047). The duration of fever was 68.0 ± 2.8 h in 1th group and 77.1 ± 2.9 h in 2nd group (p = 0.044), muscle pain – 52.3 ± 2.3 and 60.6 ± 2.6 h (p = 0.041), headache-52.1 ± 2.6 and 65.1 ± 2.5 h (p = 0.032), weakness – 75.5 ± 2.3 and 90.4 ± 2.5 h (p = 0.001), accordingly. On the 4th day of treatment the viruses were isolated in 37.8 ± 5.9% of cases in the 1st group and 57.1 ± 6.2% in 2nd group; p = 0.048. Bacterial complications were observed in 3.0 ± 2.1% and 12.6 ± 4.2% accordingly, p = 0.048. Conclusion: The study is demonstrated the effectiveness of EI in the treatment of influenza and ILI in adult outpatient patients. The antiviral and anti-inflammatory effects of the drug, which was administered within 48 h of the symptoms onset were demonstrated by a more rapid reduction of clinical symptoms, frequency of bacterial complications and reduction in the time of virus elimination. Continuation of EI clinical trials are necessary for more full evaluation of its effectiveness.

Anti-viral activity of enisamium iodide against viruses of influenza and ARVI's on different cell lines

Characterization of the antiviral properties of enisamium iodide against human respiratory viruses in in vitro experiments. In the course of experiments, the cytotoxic properties of enisamium iodide were studied against the cell lines Vero, MA-104, A549, L-41 and HEp-2. The antiviral activity of enisamium iodide was studied using virus yield reduction assay against influenza viruses, parainfluenza virus, respiratory syncytial virus, Coxsackie B3 and Coxsackie B4 viruses, as well as adenoviruses types 5 and 6. The most sensitive to the action of enisamium iodide was the human parainfluenza virus, whose activity decreased by 2.3 orders of magnitude under the action of the drug in A549 cells. Of the cell cultures used, enisamium iodide exhibited the maximum antiviral effect in human lung carcinoma cells A549, where, in its presence, the level of reproduction of adenoviruses of types 5 and 6, Coxsackie viruses B3 and B4, and human parainfluenza virus decreased by an order of magnitude or more. The antiviral activity of enisamium iodide was least manifested in Vero cells. According to the results of in vitro experiments, enisamium iodide can be considered as an antiviral drug with a wide spectrum of activity against human respiratory viruses.

Clinical and immunological efficacy of the drug Nobazit® (enisamium iodide) in the complex therapy of acute respiratory viral infections

The term «acute respiratory viral infections» refers to a group of diseases whose etiological agents are respiratory viruses, mainly affecting the epithelium of the upper respiratory tract. The article presents the results of studying the effectiveness of the drug Nobazit® in 32 patients with body temperature &gt; 37.5 °C having at least one catarrhal symptom (cough, rhinitis, or sore throat) and one symptom of intoxication (chills, sweating, malaise, weakness, or headache) who consulted a doctor within the first 48 hours from the onset of symptoms of an acute respiratory viral infection. The use of the drug Nobazit® (enisamium iodide) allowed to reduce the severity of clinical manifestations, eliminate lymphopenia, normalize factors of innate and adaptive immunity, and restore the receptor landscape of peripheral blood lymphocytes. The registered clinical and immunological efficacy of the drug Nobazit® allows recommending its inclusion in the complex therapy of acute respiratory infections.

Development of Technology and Equipment for Enisamium Iodide Drying

A methodological approach to selecting the optimal drying method for enisamium iodide, an antiviral agent with a broad spectrum of pharmacological activities, is considered. A vacuum drying method in an apparatus with a tape mixing device is proposed and verified based on studies of the main properties of the product. An industrial setup prototype and design features of the apparatus are described. The basic technological regimes of enisamium iodide drying ensuring the product quality are established. The kinetic drying and heating curves of the product, including those in the optimal regime, are presented. Test results were used to determine the specific technical parameters of the setup operation.

Some aspects of enisamium iodide nasal spray safety: pre-clinical study results

The aim. To substantiate the safety using of the new nasal spray with Enisamium Iodide via study results of acute local drug-induced irritant action of the test object single-dose to eyes and nasal cavity mucosa.Material and methods. Enisamium Iodide 10 mg/mL (nasal spray) was the test object. The reference drug was 0.9 % saline. Flemish Giant rabbits were used to induce the experiment (2 groups, 9 rabbits in each group). All study objects were administered in single-dose into the eye conjunctival sacs (0.01 mL) and nasal passages (0.1 mL) by instillation. The eye examination we performed in different time observation point (through 1, 24, 48 and 72 h after drug instillation). Nasal endoscopy was used for control of nasal cavity in all stages of study (15 minutes before, 1-hour and 24 hours after drug instillation) under general anesthesia. The scales of the assessment were used to the result objectivity.Results. The total score was 0 points in all groups at all-time points according to the relevant scale and the scale of the assessment of rabbit nasal cavity mucosa by nasal endoscopy results. This corresponds to the condition of a healthy eye and healthy nasal mucosa.Conclusions. Enisamium Iodide 10 mg/mL (nasal spray) in the single-dose instillation into the rabbit eye conjunctival sacs and rabbit nasal passages did not show local drug-induced irritant action on the eye conjunctiva and nasal cavity mucosa in the experimental animals. Nasal endoscopy could be used as an informative visual method in preclinical studies

Nasal endoscopy prospectsin experimental rhinology: some aspects of enisamium iodide nasal spray effectiveness in rhinosinusitis

Acute rhinosinusitis treatment and prevention is connected to the rational choice of drug dosage form, which will provide the therapeutic effect and the safety of a drug substance or a drug substance complex. Nasal spray with Enisamium Iodide can be used to nasal congestion relief in acute rhinosinusitis because the active substance has an anti-exudative action. Nasal endoscopy could be used in experimental rhinology as a method for direct pathology visualization and for evaluation of the effectiveness of test drugs. Aim: To substantiate Enisamium Iodide (nasal spray) 10 mg/mL effectiveness on maxillary sinus ostium via nasal endoscopy in rabbits with experimental rhinosinusitis. Methods: As a test object was used Enisamium Iodide (nasal spray). As a reference drug, we used BNO-101. Experimental rhinosinusitis was induced in the 1st day. On the 1st , 15th and 25th days in all groups (four groups, six rabbits in each group), we used nasal endoscopy and semi-quantitative assessment to the result objectivity. Results: The total score in the intact control group was 0 (0÷0) on the 15th and 25th days (physiological state). The total score in the control pathology group was 2.0 (2.0÷2.0) and 2.0 (1.0÷2.0) (severe rhinosinusitis) respectively. The total score in Enisamium Iodide treated group was 2.0 (1.0÷2.0) (severe rhinosinusitis) and 0.0 (0.0÷1.0) (physiological state). The total score in BNO-101 treated group was 2.0 (1.0÷2.0) (severe rhinosinusitis) and 1.0 (1.0÷1.0) (mild rhinosinusitis). Conclusions: Nasal endoscopy can be used as an informative visual method. Enisamium Iodide (nasal spray) has been shown a positive effect by endoscopic evaluation of maxillary sinus ostium and exceeded activity of the reference drug.

Evaluation of the effectiveness of ARVI treatment regimen including etiotropic (enisamium iodide) and symptomatic treatment

To assess the effectiveness of the use of the antiviral drug enisamium iodide in the complex treatment of acute respiratory viral infections (ARVI) caused by various pathogens in routine clinical practice. А prospective randomized study included 134 patients who were treated in the epidemic season of influenza and ARVI in 20182019. All patients were examined for the presence of influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, rhinoviruses, adenoviruses in nasopharyngeal swabs by PCR. Patients of the main group received enisamium iodide along with symptomatic therapy, the control group received only symptomatic therapy. The primary parameter of the effectiveness of therapy was evaluated on the scale of the general severity of the manifestations of ARVI (Total Symptom Score TSS) from the 2nd to the 4th day and by the secondary criteria of effectiveness: assessment of the duration of ARVI, the severity of fever, the proportion of patients with normal body temperature, the duration of the main clinical symptoms of acute respiratory viral infections, the proportion of patients in whom complications requiring antibiotics were noted, the dynamics of interferon status on the 6th day. To conduct a statistical analysis, depending on the efficiency parameter, the ANCOVA method with a fixed group factor and an initial score on the TSS severity scale was used as covariates, a criterion for comparing quantitative indicators in two independent groups. According to the results of the analysis of the primary efficacy parameter, the median (interquartile range) of the average score on the scale of the general severity of ARVI manifestations in the main group was 4.33 (3.675.83), in the comparison group 6.00 (4.677.25; p0.001). The duration of systemic and local manifestations of acute respiratory viral infections was statistically significantly less in the main group (p=0.002 and p=0.019, respectively). Prescription of additional therapy was required in 2 (2.9%) patients of the main group (patients taking enisamium iodide), compared with 8 (11.9%) patients in the control group. Serum levels of interferon  and interferon  on the last day of treatment were statistically significantly higher in patients of the main group compared with the control group (p0.001). Treatment (excellent) was evaluated by 42 (62.7%) patients, while in the control group only 17 (25.8%) patients gave similar ratings. Both patients (p0.001) and doctors (p0.002) rated therapy tolerance better in the study group. The results confirmed the safety and effectiveness of enisamium iodide as a treatment for ARVI and influenza. The antiviral, interferonogenic and anti-inflammatory properties of the drug are involved in the formation of an antiviral response and reduce the risk of complications, which makes it possible to reduce the number of symptomatic agents used.

Review of current and future directions of antiviral therapy of influenza and acute respiratory viral infections in Russia

to determine the perspectives for the use of drugs with combined antiviral, anti - inflammatory and immunomodulatory activity on the basis of medical studies of existing antiviral drugs for the treatment of influenza and acute respiratory viral infections in Russia. A brief review of the antiviral drugs used in Russia for the treatment of influenza and acute respiratory viral infections was conducted on the basis of 37 articles published in Scopus, Web of Science (WoS), and RSCI databases in the period from 1997 to 2018. Resistance to neuraminidase inhibitors (oseltamivir, zanamivir), is slowly developing due to the mutations of the neuraminidase gene H275Y and Q136K. Most influenza A viruses remain resistant to adamantane antivirals. Repeated use of immunomodulators with indirect antiviral action leads to a hyporeactivity of the immune system and, subsequently, to a decrease in their effectiveness. Positive clinical and laboratory data in clinical trials were obtained using Enisamium iodide, a drug with combined action - direct antiviral, and immunomodulatory. According to the WHO strategy, the results of the review demonstrate the need for continued research of medications with combined antiviral and pathogenetic effects on the infectious process caused by influenza and acute respiratory viral infections.

The preclinical study of a new nasal spray with the anti-inflammatory properties: the effect on the leukotriene-induced inflammation

The use of medicines of the local action with complex effects on the pathogenic cascade of acute rhinosinusitis (ARS) is expedient. Farmak Joint-Stock Company (Ukraine) has developed a new original dosage form of a nasal spray, which contains an aqueous solution of the known pharmaceutical substance Enisamium Iodide (EI). The presence of the effect on the leukotriene link inflammation in EI can determine the high rate of the antiexudative action development in the topical (intranasal) application. This may be useful for pathogenetic therapy of ARS on the background of acute respiratory viral infections taking into account the potential effectiveness for nasal congestion relief. Aim. To substantiate experimentally the expediency of application of a new nasal spray with EI under conditions of leukotriene-induced exudative inflammation. Materials and methods . A new nasal spray EI (JSC Farmak (Ukraine)) – “Amizon” – with the active substance concentration of 10 mg/ml was chosen as the study object. Ibuprofen – “Nurofen” (Reckitt Benckiser Helchere International Limited (UK)), film-coated tablets, 200 mg – was used as the reference drug and was administered once daily in the dose of 48 mg/kg intragastrically. The study of anti-inflammatory properties of EI (nasal spray, 10 mg/ml) in the external (epicutaneous) application was performed on white nonlinear rats of both genders in the experimental zymosan-induced inflammation development. The anti-inflammatory activity (AIA) of EI (nasal spray, 10 mg/ml) compared to Ibuprofen was assessed in percentage in dynamics in 0.5, 1 and 2 hours of observation. Results. According to the results of the studies conducted EI in the dosage form of a nasal spray in the active substance concentration of 10 mg/ml on the model of zymosan-induced inflammation of the rat foot showed the anti-inflammatory properties. According to the degree of its anti-inflammatory properties EI was not inferior to the reference drug Ibuprofen, but even exceeded its activity as of the 30 th minute of observation after zymosan injection. The result obtained allows suggesting the presence of high rate of the antiexudative action in the experimental object in the topical (intranasal) application in the treatment of patients with ARS due to the ability to inhibit the lipoxygenase route of the arachidonic acid metabolism. Conclusions . The presence of the anti-inflammatory activity of Enisamium Iodide (nasal spray) has been proven under conditions of leukotriene-induced inflammation reproduction on the model of the zymosan edema. By expression of the anti-inflammatory action during all periods of observation EI is not inferior to the reference drug Ibuprofen, exceeding the activity of the classical NSAID by 1.5 times as of the 30 th minute after the pathology onset. The anti-inflammatory activity of Enisamium Iodide in the dosage form of nasal spray experimentally substantiates the expediency and perspectivity of its further preclinical studies.

Досвід використання енісаміуму йодиду в клініці гострих респіраторних захворювань: огляд літератури

Досвід використання енісаміуму йодиду в клініці гострих респіраторних захворювань: огляд літератури

Validation of the method for determination of related impurities in the active antiviral ingredient of enisamium iodide

The aim of the work. To validate a method for the related impurities determination in the enisamium iodide active pharmaceutical ingredient (API) by means of high-performance liquid chromatography (HPLC). To characterize the sensitivity of the method by establishing the limit of detection and limit of quantification for the following impurities: benzylamine, isonicotinic acid (raw materials for API synthesis), isonicotinic acid benzylamide (intermediate product of API synthesis) and unidentified impurities. To confirm the method compatibility with validation characteristics as recommended by the International Conference on Harmonization of Technical Requirements for the Registration of Medicinal Products for Human Use (ICH). Materials and methods. The liquid chromatograph Agilent 1200 equipped with degasser, four-channel pump, auto sampler, chromatographic column thermostat and diode array detector was used. The Zorbax Eclipse XDB-C18 chromatographic column with dimensions 150.0 ×4.6 mm filled by octadecylsilane sorbent with a particles size of 5 μm, was used. The mobile phase was a mixture of a buffer solution pH 2.5 containing sodium octane-1-sulfonate in an amount of 0.1 %: water : acetonitrile (30 : 44 : 26 v/v/v). The primary standards of Farmak JSC were used: enisamium iodide (b. 07-16) and isonicotinic acid benzylamide (b. 10413). Other materials and reagents were used with sufficient purity (Sigma-Aldrich). Results. Detection limits and limits of quantification for identified and unidentified impurities have been determined. Validation characteristics such as specificity, accuracy, precision, range of use, robustness, intermediate precision have been confirmed. The linearity has been confirmed within the range of 0.01–0.06 % for each of the impurities (with a maximum permitted content of each impurity of 0.05 %). The correlation coefficients of linear regression (r) between the entered and found values for each of the determined impurities are greater than 0.990 and the relative confidence intervals ( D z ) are at the level not more than 5.0 %. Stability of the test solution, reference solution and solution for system suitability test upon storage at room temperature for 48 hours have been confirmed. Conclusions. It has been experimentally proved that the described method can be used for quality control of enisamium iodide substance.

Development and validation of the method quantitative determination of enisamium iodide for the assessment of dissolution profile of antiviral agent

Assessment of the dissolution profiles is an important tool for characterization of solid drug products which need to be examined both at the stage of pharmaceutical development, and throughout their life cycle. It is necessary to control the release of the active substance from the dosage form after changes which are related to variation of drug product composition or technology used.&#x0D; The aim of this work was to develop and validate a method for the study of dissolution profiles of the antiviral agent enisamium iodide, tablets.&#x0D; The liquid chromatograph Agilent 1260 (USA) equipped with degasser, four-channel pump, autosampler, chromatographic column thermostat and diode area detector was used. The chromatographic column Zorbax Eclipse XDB-C18, with dimensions 150 × 4.6 mm, filled by octadecylsilane sorbent, with a particles size of 5 μm, was used. The mobile phase is a mixture of a buffer solution of pH 2.5 containing sodium octane-1-sulfonate in an amount of 0.1%, water, acetonitrile (30:35:35 v/v/v). The dissolution tester ERWEKA DT 820 (Germany) was also used.&#x0D; During the validation such parameters as specificity, accuracy, precision and robustness were confirmed. The correlation coefficients of linear regression (r) between the entered and found values for enisamium iodide is greater than 0.995.&#x0D; Stability of the reference solutions and test solutions at storage at room temperature for 24 hours has been confirmed.&#x0D; The developed HPLC method of the quantitative determination of enisamium iodide can be used for study of the dissolution profiles of enisamium iodide tablets.