The possibility of preventive and therapeutic use of green tea catechins in prostate cancer

Background: Prostate cancer is one of the most frequent types of cancer. Despite the existence of various treatment strategies, treatment of prostate cancer still presents serious difficulties (especially in advanced stages). Polyphenols have been extensively assessed in terms of their potential use for prostate cancer treatment and prevention. Catechins are among the most well-known polyphenols in this respect. Objective: In this review, we summarize clinical study results concerning catechin applications with regard to prostate cancer treatment and prevention. We discuss some of the main mechanisms of the anticarcinogenic action of catechins. Conclusion: The main mechanisms of the anticarcinogenic action of catechins are subdivided into two major types: (i) direct action on cancer cells and (ii) indirect effect based on catechins’s impact on the microenvironment of cancer cells, particularly in relation to the immune system. At this level catechins might reduce tumor-associated inflammation and immune tolerance. © 2019 Bentham Science Publishers

Evaluation of the toxicity of new progestogen gestobutanoil in experiments on rats and mice

A toxicological study of gestobutanoil tablets containing 0.002 g of progestogen 17a-acetoxy-3b-hydroxy-6-methylpregna-4,6-dien-20-one in the form of butyl ester as an active pharmaceutical substance for peroral administration was carried out on mice and rats of both sex. It was found that LD 50 of the drug exceeded 5 g/kg, which indicated low toxicity of gestobutanoil tablets. Chronic intragastric administration of gestabutanoil in doses of 2.5 and 25 mg/kg for 30 days did not cause clinically significant changes in the integral state of animals, biochemical and hematological parameters, except for an increase in the concentration of direct bilirubin in the blood by 37-40% (p - 0,01), which is a characteristic biochemical feature of gestagen-containing drugs. The observed tendency to decrease in the locomotor, orientation, and research activity and emotional behavior of female rats upon the administration of gestabutanoil for a month indicates its possible antistress effect on the central nervous system of rats. A specific effect of the drug in the studied doses 2.5 and 25 mg/kg on the target organs (uterus and ovaries) was revealed, as manifested by decidualization of the endometrium and a decrease in folliculogenesis in the ovaries. Since no toxic effect was observed in doses of 2.5 and 25 mg/kg (which exceeded the therapeutic dose 10 and 100 times, respectively), die equivalent dose for humans can be 0.064 mg/kg/day, according to the animal-to-human dose conversion formula. © 2018 Izdatel'stvo Meditsina. All rights reserved

HPLC-MS Method for Simultaneous Quantitative Determination of an Innovative Russian Gestagen and its Metabolites in Rat and Rabbit Blood Sera

An HPLC-MS method for simultaneous quantitative determination of a novel gestagenic pharmaceutical and two of its metabolites in rat and rabbit blood sera was developed and validated. The method was selective and specific. The detection limit for all analytes was 5 ng/mL; lower limit of quantitation, 10 ng/mL. Calibration curves for all analytes had the form y = ax + b. The correlation coefficients were >0.99. Matrix effects, degree of extraction, and stability of analytes in standard solutions, analytical samples, and the biomatrix with multiple freeze—thaw cycles were studied. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

ВЭЖХ-МС методика одновременного количественного определения инновационного отечественного гестагена и его метаболитов в сыворотке крови крыс и кроликов

A method for simultaneous quantitative determination of a new gestagenic pharmacological agent and its two metabolites in the blood serum of rats and rabbits by HPLC-MS has been developed and validated. The method is selective and specific. The detection limits of all analytes were 5 ng/mL and the lower limits of quantification were 10 ng/mL. The calibration curves for all analytes had the form of y = ax + b with correlation coefficients > 0.99. The matrix effect and degree of extraction were studied, as well as the stability of analytes in standard solutions, ready-for-analysis samples, and biomatrix during repeated freezing and thawing cycles.Разработана и валидирована ВЭЖХ-МС методика одновременного количественного определения нового гестагенного фармакологического средства и 2 его метаболитов в сыворотке крови крыс и кроликов. Метод селективен и специфичен. Предел обнаружения для всех аналитов составил 5 нг/мл, нижний предел количественного определения - 10 нг/мл. Для всех аналитов калибровочные кривые имели вид: y = ax + b. Коэффициенты корреляции > 0,99. Изучены эффект влияния матрицы и степень извлечения, а также стабильность аналитов в стандартных растворах, готовых пробах и биоматрице при многократном замораживании и размораживании

О вторичном патентовании органических соединений, пригодных для использования в качестве активных фармацевтических субстанций

The problem of secondary patenting of organic compounds that can undoubtedly be used as active pharmaceutical substances (APSs) is considered. Such compounds, their synthetic pathways, and potential applications as APSs are usually several years before obtaining official permission for using the related drugs in practical medicine. This time lag frequently stimulates attempts at illegal secondary patenting of these APSs by other applicants. These attempts can be successful because of a low level of patent expertise. As a rule, secondary patents contain non-confirmed experimental data and numerous errors that are indicative of the lack of proper professional skill of both new patent applicants and new experts. With a view to drawing the attention of scientific community to this problem, we consider examples of secondary patents that were granted for six vital drugs containing original APSs of abacavir sulfate, darunavir, dasatinib, lenalidomide, apalutamide, and enzalutamide. It is shown that the appearance of illegal secondary patents is impermissible from scientific, ethical, and legal viewpoints.Рассмотрена проблема вторичного патентования органических соединений, возможность применения которых в качестве активных фармацевтических субстанций (АФС) не вызывает сомнений. Такие соединения, пути их синтеза и возможного использования в качестве АФС, как правило, патентуются на несколько лет раньше получения официального разрешения на применение содержащих их препаратов в медицинской практике. Этот разрыв во времени стимулирует попытки незаконного вторичного патентования таких АФС новыми заявителями. Эти попытки приводят к успеху из-за крайне низкого уровня патентной экспертизы. Как правило, вторичные патенты содержат неподтверждённые экспериментальные данные и изобилуют ошибками, свидетельствующими об отсутствии должной профессиональной подготовки как заявителей, так и экспертов. С целью привлечь внимание научной общественности к проблеме, ниже она в разных аспектах рассмотрена на примере вторичных патентов, выданных на 6 жизненно важных лекарственных препаратов, содержащих в качестве АФС: абакавира сульфат, дарунавир, дазатиниб, леналидомид, апалутамид и энзалутамид. Показано, что появление подобных патентов с научной, этической и правовой точек зрения не допустимо

On Secondary Patenting of Organic Compounds Suitable for use as Active Pharmaceutical Ingredients

Secondary patenting of organic compounds that can undoubtedly be used as active pharmaceutical ingredients (APIs) is discussed. As a rule, such compounds, their synthetic pathways, and potential applications as APIs are patented several years before official authorization to use medicines containing them is obtained. This time lag stimulates attempted illegal secondary patenting of such APIs by new applicants. These attempts can be successful because of the extremely low level of patent review. As a rule, secondary patents contain unconfirmed experimental data and numerous errors, indicating that the applicant and experts lack sufficient professional training. In order to draw the attention of the scientific community to the problem, various aspects of it are discussed below using as examples secondary patents granted for six vitally important drugs used as APIs: abacavir sulfate, darunavir, dasatinib, lenalidomide, apalutamide, and enzalutamide. The appearance of such patents is shown to be inadmissible from scientific, ethical, and legal viewpoints. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

The Role of Autophagy and Apoptosis in the Combined Action of Plasma-Treated Saline, Doxorubicin, and Medroxyprogesterone Acetate on K562 Myeloid Leukaemia Cells

The anti-cancer properties of plasma-treated solutions (PTS) and their interaction with drugs are one of the most popular topics in modern plasma medicine. Our research involved comparing the effects of four physiological saline solutions (0.9% NaCl, Ringer’s solution, Hank’s Balanced Salt Solution, Hank’s Balanced Salt Solution with amino acids added in concentrations observed in the human blood) treated with cold atmospheric plasma and studying the combined cytotoxic effect of PTS with doxorubicin and medroxyprogesterone acetate (MPA). Analysis of the effect of the studied agents on the formation of radicals in the incubation medium, the vitality of K562 myeloid leukaemia cells, and the processes of autophagy and apoptosis in them revealed two key findings. The first is that when using PTS and doxorubicin-containing PTS, autophagy is the predominant process in cancer cells. The second is that combining PTS with MPA enhances apoptotic processes. It was hypothesised that while autophagy is stimulated by the accumulation of reactive oxygen species in the cell, apoptosis is stimulated through specific cell progesterone receptors