КОНЦЕПЦИЯ СЛОЖНЫХ НЕБИОЛОГИЧЕСКИХ ЛЕКАРСТВЕННЫХ СРЕДСТВ ПРИ РАЗРАБОТКЕ ВОСПРОИЗВЕДЕННЫХ ПРЕПАРАТОВ

Expansion of the range of new medicines leads to a significant increase in healthcare spending and, consequently, to the appearance of more affordable generic drugs. A drug can be recognised as generic if there is sufficient evidence of equivalent structural characteristics of the active substance and therapeutic characteristics of the drug. However, for a number of substances which are multicomponent mixtures of sister compounds it is quite difficult to demonstrate absolute similarity of the chemical structure and to determine a substrate for bioavailability evaluation. Therefore, a separate group of non-biological complex drugs has been singled out. The present article summarises the requirements of the leading regulatory agencies for demonstration of equivalence between the reference product and such medicines as glatiramoids, liposome-encapsulated doxorubicin and iron-based nanosized colloidal products. It has been shown that preclinical and clinical studies are still necessary for these types of products, and the amount of testing will depend on the results of comparability assessment.Расширение спектра новых лекарственных препаратов приводит к существенному повышению затрат на здравоохранение и, как следствие, появлению воспроизведенных препаратов с более выгодными ценовыми характеристиками. Признание препарата воспроизведенным возможно при наличии достаточных доказательств эквивалентности структурных характеристик действующего вещества и терапевтических характеристик лекарственного препарата. Однако для ряда веществ, представляющих собой многокомпонентную смесь близких по строению соединений, появляется сложность доказательства абсолютного сходства химической структуры и, соответственно, определения субстрата для оценки биодоступности. В связи с этим выделяют отдельную группу сложных небиологических препаратов. В данной статье рассмотрены основные требования ведущих мировых регуляторных органов к доказательству сходства с референтным продуктом препаратов глатирамера ацетата, липосомальных препаратов доксорубицина и наноколлоидных препаратов железа. Показано, что для этих препаратов остается необходимым проведение доклинических и клинических исследований, объем которых определяется на основании оценки их сопоставимости

Information system on microbial collections as a part of bioresource collections portal for Russia’s FASO organizations: a working protocol

Nowadays, many scientific organizations of Russia own collections of microorganisms on which large volumes of information have been generated. These data represent the descriptions of objects of diverse nature (bacteria, archaea, fungi, protists) and their properties, which have been carefully collected and cataloged by generations of researchers. Not every organization that has such collections has an open access electronic catalog, which not only complicates work with these unique materials, but also even hides the fact of the existence of such collections. This state of affairs requires the development of electronic resources for presenting these materials to the scientific community. To put together the information on microorganism collections, we have developed an internet portal (http://www.biores.cytogen.ru/microbes/) of microbial bioresource collections of FASO organizations in the Russian Federation. The portal was created under the project developing the information system for bioresource collections of FASO institutes. It is a platform where collection organizations can place information about the storage units of their collections, as well as other information on collections, including links to their own catalogs. In this paper, we describe the principles of working with the portal. The portal’s graphical interface allows users, both registered and unregistered, to receive the following information about collections of microorganisms: a list of collections represented in the database, contact details of the organization and information about the curator of the collection, summary statistics for each collection, as well as information on storage units. Registered users – owners of collections – have the opportunity to create and modify records about the storage units of their collections, and to update their description. To automate work with the portal, software access to the database through the REST API has been implemented (http://api.biores.cytogen.ru/ microbes/). At present, the portal is still being filled, but it already contains a description of more than 13,000 items of storage (of which 3500 are in the microorganisms’ part) of 65 bioresource collections in Russia’s FASO organizations. Of these collections, 12 with microorganisms have a total diversity of funds of about 50,000 strains)

An integrated method for taxonomic identif ication of microorganisms

For accurate species-level identification of microorganisms, researchers today increasingly use a combination of standard microbiological cultivation and visual observation methods with molecular biological and genetic techniques that help distinguish between species and strains of microorganisms at the level of DNA or RNA molecules. The aim of this work was to identify microorganisms from the ICG SB RAS Collection using an integrated approach that involves a combination of various phenotypic and genotypic characteristics. Key molecular-genetic and phenotypic characteristics were determined for 93 microbial strains from the ICG SB RAS Collection. The strains were characterized by means of morphological, physiological, moleculargenetic, and mass-spectrometric parameters. Specific features of the growth of the strains on different media were determined, and cell morphology was evaluated. The strains were tested for the ability to utilize various substrates. The strains studied were found to significantly differ in their biochemical characteristics. Physiological characteristics of the strains from the collection were identified too, e. g., the relationship with oxygen, type of nutrition, suitable temperature and pH ranges, and NaCl tolerance. In this work, the microorganisms analyzed were combined into separate groups based on the similarities of their phenotypic characteristics. This categorization, after further refinement and expansion of the spectrum of taxa and their metabolic maps, may serve as the basis for the creation of an “artificial” classification that can be used as a key for simplified and quicker identification and recognition of microorganisms within both the ICG SB RAS Collection and other collections

Russian clinical practice guidelines «congenital adrenal hyperplasia»

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases characterized by a defect in one of the enzymes or transport proteins involved in the cortisol synthesis in the adrenal cortex. The most common form of CAH, which occurs in more than 90% of cases, is a 21-hydroxylase enzyme deficiency. The latter is subdivided into nonclassical and classic (salt-losing and virilizing) forms. The prevalence of classic forms of 21-hydroxylase deficiency ranges from 1: 14,000 to 1:18,000 live births worldwide. According to the data of neonatal screening in the Russian Federation, the prevalence of the disease in some regions ranges from 1: 5000 to 1: 12000, in the country as a whole - 1: 9638 live newborns. The non-classical form of CAH occurs more often - from 1: 500 to 1: 1000 among the general population. In second place is the hypertensive form of CAH - a deficiency of 11β-hydroxylase, which, according to the literature, occurs in about 1 per 100,000 newborns. These clinical guidelines were compiled by a professional community of narrow specialists, approved by the expert council of the Ministry of Health of the Russian Federation, and updated the previous version published in 2016. The clinical guidelines are based on systematic reviews, meta-analyses and original articles, and scientific work on this issue in the Russian Federation and other countries. The purpose of this document is to provide clinicians with the most up-to-date, evidence-based guidelines for the CAH diagnosis and treatmen

NON-BIOLOGICAL COMPLEX DRUGS CONCEPT IN GENERIC DRUGS DEVELOPMENT

Expansion of the range of new medicines leads to a significant increase in healthcare spending and, consequently, to the appearance of more affordable generic drugs. A drug can be recognised as generic if there is sufficient evidence of equivalent structural characteristics of the active substance and therapeutic characteristics of the drug. However, for a number of substances which are multicomponent mixtures of sister compounds it is quite difficult to demonstrate absolute similarity of the chemical structure and to determine a substrate for bioavailability evaluation. Therefore, a separate group of non-biological complex drugs has been singled out. The present article summarises the requirements of the leading regulatory agencies for demonstration of equivalence between the reference product and such medicines as glatiramoids, liposome-encapsulated doxorubicin and iron-based nanosized colloidal products. It has been shown that preclinical and clinical studies are still necessary for these types of products, and the amount of testing will depend on the results of comparability assessment

THEORETICAL AND PRACTICAL ISSUES OF BIOLOGICAL OXIDATION OF HYDROCARBONS BY MICROORGANISMS

The paper deals with the theoretical issues of biological oxidation of oil hydrocarbons from alkanes to polycyclic aromatics. We analyze the mechanisms of biochemical processes of decomposition of oil components and provide an overview of data from common databases. Studies of microbial communities of natural oil seeps in the Uzon caldera are described in detail. It is the first study of ecophysiological characteristics of oil-degrading microorganisms isolated from thermal oil seeps of the caldera

Copper( ii ) complexes with phosphorylated 1,10-phenanthrolines: from molecules to infinite supramolecular arrays

International audienceThe reaction of phosphorylated 1,10-phenanthrolines 3-Pphen, 3,8-Pphen and 4,7-Pphen (3-Pphen = 3-diethoxyphosphorylphenanthroline, 3,8-Pphen = 3,8-bis(diethoxyphosphoryl) phenanthroline, 4,7-Pphen = 4,7-bis(diethoxyphosphoryl) phenanthroline) and hydrated copper(II) nitrate in a 1 : 1 ratio leads to the formation of supramolecular architectures. In the 1D coordination polymer [Cu(3-Pphen)(NO3)(2)](n) (2) the copper atom is coordinated to only one phenanthroline ligand and the coordination sphere is completed by two oxygen atoms of nitrate anions and the oxygen atom of the phosphoryl group from the neighbouring phenanthroline ligand. Complex Cu(3,8-Pphen)(NO3)(2) (3) crystallizes from dichloromethane/ether in two polymorphic forms. Form 3-I is a dimeric complex in which two phenanthroline rings are parallel and offset-shifted due to the formation of two (P) O-Cu bonds. The crystals of the polymorph 3-II are composed of polymeric chains in which the coordination sphere of the metal centres and the arrangement of the mononuclear fragments are similar to those of complex 2. Complex [Cu(4,7-Pphen)(NO3)(2)](2) (4) crystallizes from toluene/acetonitrile and exhibits a dimeric structure which is similar to that of 3-I