Способ получения соли олигогексаметиленгуанидина высокой степени чистоты

Objectives. Given that microorganisms can become resistant to certain groups of drugs and considering also their ability to form biofilms, the development of new drugs that are active against adapted microflora is required. This study focused on the development of a new method for the synthesis of a promising compound, the branched hydrosuccinate oligohexamethylene guanidine (OHMGsucc), with high purity that meets the standards of the 14th edition State Pharmacopeia of the Russian Federation (SPRF). Previously proposed methods have managed to isolate this product, which, however, complies with the requirements of the outdated SPRF. Therefore, the main aim of this study was to update the regulatory framework for the indicated OHMG salt for its further use in the pharmaceutical industry according to modern standards.Methods. To control the residual impurities of hexamethylenediamine (HMDA) and guanidine hydrochloride (GHC), high-performance liquid chromatography (HPLC) was applied using a Thermo Scientific Dionex UltiMate 3000 chromatograph, and the chromatographic signals of the test solution with those of a standard sample solution obtained by a previously published conventional method were compared.Results. The HPLC experimental data indicated a significant difference in the quantitative content of HMDA and GHC observed for the new and older preparation method of the branched OHMGsucc, suggesting that the method disclosed in this article can be used to obtain highly pure OHMGsucc.Conclusions. The specified compound was standardized with the parameter “related impurities” according to the current (14th) edition of the SPRF. The effectiveness and reproducibility of the proposed method was experimentally confirmed. In addition, a process diagram for the preparation of the indicated OHMG salt was prepared.Цели. На фоне приобретения микроорганизмами резистентности к определенным группам лекарственных средств, а также способностей образовывать биопленки, требуются новые препараты, активные против адаптированной микрофлоры. Cтатья посвящена изысканию способа получения перспективного соединения – разветвленного гидросукцината олигогексаметиленгуанидина с высокой степенью чистоты, соответствующей нормам Государственной Фармакопеи 14 издания. Так как предложенные ранее методы позволяли получить продукт, удовлетворяющий требованиям устаревшей Государственной Фармакопеи, то основной целью являлась актуализация нормативной базы в отношении указанной соли олигогексаметиленгуанидина для ее дальнейшего применения в фармацевтической отрасли согласно современным стандартам.Методы. Для контроля примесных соединений – гексаметилендиамина и гуанидина гидрохлорида применяли высокоэффективную жидкостную хроматографию, которую проводили на хроматографе Thermo Scientific Dionex UltiMate 3000 методом внешнего стандарта.Результаты. На основании экспериментальных данных, полученных с помощью высокоэффективной жидкостной хроматографии, отображена разница в количественном содержании остаточных примесей в составе субстанции разветвленного гидросукцината олигогексаметиленгуанидина, полученной двумя разными способами. Отмечено, что способ, предложенный авторами настоящей статьи, позволяет снизить их содержание по сравнению с конвенциональным методом.Выводы. Согласно представленным данным проведена стандартизация указанного соединения по параметру «Родственные примеси» в соответствии с актуальным на данный момент изданием Государственной Фармакопеи. Вследствие того, что эффективность предложенного метода экспериментально подтвердилась, на заключительном этапе работы была составлена технологическая схема получения указанной соли олигогексаметиленгуанидина

Dynamics of vegetative, insomnia and neuropsychological manifestations during the treatment of post-COVID syndrome

Introduction. Asthenia, vegetative manifestations, sleep disturbances and psycho-emotional background are companions of the coronavirus infection, the issue of drug correction of which is especially relevant. These symptoms disrupt the habitual way of life of patients for a long time, and in special cases lead to disability.Aim. To study the mental, somatoform and cognitive aspects of anxiety disorders after coronavirus infection during treatment with tofisopam (Grandaxin®) 150 mg/day.Materials and methods. The study included patients who had experienced a new coronavirus infection, who, after the end of treatment for the underlying disease, had complaints suggesting the presence of an anxiety disorder. The Hamilton scale was used to assess the level of anxiety. Examination of patients was carried out before the start of treatment, after 2, 4 and 6 weeks of therapy.Results and discussion. Prior to the start of therapy, all patients had an overall high level of anxiety: the average HAM-A score was 31.4 ± 2.92 points. At the end of Grandaxin® therapy, all patients showed a decrease in the level of anxiety: the average HAM-A score was 12.08 ± 2.27 points (p < 0.001). The maximum decrease in the severity of vegetative disorders was noted by the end of the 6th week of therapy with Grandaxin®. Thus, the indicator of this subscale decreased by more than 2 times – from 2.46 ± 0.54 to 1.05 ± 0.28 points (p < 0.001). The severity of insomnia during six weeks of therapy with Grandaxin® decreased from 2.56 ± 0.54 to 0.96 ± 0.45 points (p < 0.001).Conclusion. Psycho-emotional disorders (more often in the form of increased personal anxiety), sleep disorders, vegetative disorders, asthenic syndrome significantly affect the quality of life of patients who have had a new coronavirus infection. Involvement of the structures of the autonomic nervous system and central structures that regulate GABAergic transmission leads to significant vegetative failures, which requires pathogenetically substantiated drug correction of these disorders

F-transform in View of Aggregation Functions

Abstract A relationship between the discrete F-transform and aggregation functions is analyzed. We show that the discrete F-transform (direct or inverse) can be associated with a set of linear aggregation functions that respect a fuzzy partition of a universe. On the other side, we discover conditions that should be added to a set of linear aggregation functions in order to obtain the discrete F-transform. Last but not least, the relationship between two analyzed notions is based on a new (generalized) definition of a fuzzy partition without the Ruspini condition.

The Prevalence of High Carcinogenic Risk of HPV Genotypes among HIV-Positive and HIV-Negative MSM from Russia

Objective. Men who have sex with men (MSM) have a high risk of lifelong anal cancer caused by high-risk human papillomavirus (HR HPV) infections. The aim of this study was to investigate the prevalence of anal canal HR HPV infection among men who have sex with men (MSM) with and without HIV infection in Moscow (Russia). We evaluated associations of some HIV coinfections (HSV and CMV) and HPV distribution among MSM with and without HIV infection. Methods. Two groups of HIV-positive (n = 60) and HIV-negative (n = 60) MSM were evaluated in the study. Fourteen high-risk (HR) HPV types, HSV1/2, and CMV were investigated in men anal swabs. Results. HR HPVs were found with nearly the same frequency of 66.7% in both groups: HIV-positive and HIV-negative MSM. HIV-positive status was statistically associated with the presence of several (more than two) HPV types (p = 0.044). The most prevalent HR HPV genotypes were HPV18, HPV16, HPV56, and HPV33 for HIV-positive MSM and HPV56, HPV51, HPV66, and HPV16 for HIV-negatives. We found a statistically significant association of five HR HPV types with HIV status of MSM: HPV16 (p = 0.028), HPV18 (p = 0.00006), HPV58 (p = 0.003), HPV33 (p = 0.019), and HPV39 (p = 0.026). The frequency of HSV1 (1.7%) and HSV2 (10%) infections and CMV (3.3%) infection was evaluated in the group of HIV-positive MSM. The frequency of HSV1 (5%) and HSV2 (6.7%) infections and CMV (0%) infection was evaluated, as well, in the group of HIV-negative MSM. Conclusion. Multiple HPV genotypes were detected significantly more often than single HPV genotype in the group of HIV-positive MSM. According to our data, 25% of HIV-positive MSM have HPV39; this is the only one of the five types of HR HPV (16, 18, 58, 33, and 39) associated with this group of MSM that has not yet been included in the HPV vaccines available on the market

An effective method for preparation of high purity oligohexamethylene guanidine salts

Objectives. Given that microorganisms can become resistant to certain groups of drugs and considering also their ability to form biofilms, the development of new drugs that are active against adapted microflora is required. This study focused on the development of a new method for the synthesis of a promising compound, the branched hydrosuccinate oligohexamethylene guanidine (OHMGsucc), with high purity that meets the standards of the 14th edition State Pharmacopeia of the Russian Federation (SPRF). Previously proposed methods have managed to isolate this product, which, however, complies with the requirements of the outdated SPRF. Therefore, the main aim of this study was to update the regulatory framework for the indicated OHMG salt for its further use in the pharmaceutical industry according to modern standards.Methods. To control the residual impurities of hexamethylenediamine (HMDA) and guanidine hydrochloride (GHC), high-performance liquid chromatography (HPLC) was applied using a Thermo Scientific Dionex UltiMate 3000 chromatograph, and the chromatographic signals of the test solution with those of a standard sample solution obtained by a previously published conventional method were compared.Results. The HPLC experimental data indicated a significant difference in the quantitative content of HMDA and GHC observed for the new and older preparation method of the branched OHMGsucc, suggesting that the method disclosed in this article can be used to obtain highly pure OHMGsucc.Conclusions. The specified compound was standardized with the parameter “related impurities” according to the current (14th) edition of the SPRF. The effectiveness and reproducibility of the proposed method was experimentally confirmed. In addition, a process diagram for the preparation of the indicated OHMG salt was prepared

Probabilistic study of Induced Ordered Linear Fusion Operators for time series forecasting

The aggregation of several predictors in time series forecasting has been used intensely in the last decade in order to construct a better resulting model. Some of the most used alternatives are the ones related to the Induced Ordered Weighted Averaging (IOWA), in which the prediction values are ordered using a secondary vector, often related to the accuracy of the prediction model in the last prediction. Although the time series study has been historically a subject related to statistics and stochastic processes, the random behaviour of the aggregation process is typically not considered. In addition, extensions of aggregation functions with a weaker notion of monotonicity, pre-aggregation functions, are appearing as better alternative for some topics such us classification. In this paper, a pre-aggregation extension of the IOWA operator, the Induced Ordered Linear Fusion (IOLF), is defined as a way to aggregate time series model predictions and its behaviour is studied from a probabilistic point of view. The IOLF operator over random vectors is defined, its properties studied and the relation between some averaging aggregation functions established. The expressions of the optimal weights according to statistical criteria are derived. The advantages and consequences of the use of the IOLF operator are studied, and its behaviour is compared to the usual procedures. Numerical results illustrate its performance on a practical example