Pub Date : 2024-08-09DOI: 10.33380/2305-2066-2024-13-3-1767
G. V. Adamov, O. L. Saybel, A. N. Babenko, E. S. Melnikov, A. I. Radimich, O. Kulyak, L. Krepkova
Introduction. The development and registration of antiviral drugs is an urgent task. Flavonoids, in particular, luteolin-7-glycoside (cinaroside, luteolin-7-O-glycoside) demonstrate high broad-spectrum antiviral activity in vitro, and the industrial regulations for the production of luteolin-7-glycoside from the leaves of holly willow have already been developed at the VILAR. One of the problems with the introduction of flavonoids into medical practice is their low bioavailability and intensive biotransformation. Existing publications provide contradictory data on the pharmacokinetics of luteolin-7-glycoside, and therefore our own research was conducted.Aim. To develop a methodology for the quantitative analysis of luteolin-7-glycoside and its metabolites in blood plasma and to test it on laboratory animals.Materials and methods. Animal experiments were carried out in accordance with the requirements of the "Guidelines for conducting preclinical studies of medicines". To develop a method of analysis and further clarify the time intervals of blood sampling, time points were analyzed: 30, 60 minutes, 2, 4, 8, 24 hours after administration of the test substance. Tubes with citrate blood of laboratory animals were centrifuged at 2000 rpm for 10 minutes. The plasma was placed in an Eppendorf-type test tube, frozen and stored at –20 °C until chromatographic analysis was performed. Blood plasma sample preparation was carried out by precipitation with methyl alcohol, the supernatant was chromatographically separated on a column Luna® 5 µm C18 column 100 Å 250 × 4.6 mm in a gradient mode in a water-acetonitrile system and a modifier – 0.2 % formic acid. The metabolites were identified by high-performance liquid chromatography with mass spectrometric detection. To do this, the spectral characteristics of the peaks that appeared on the chromatograms of blood plasma samples after oral administration of luteolin-7-glycoside were interpreted. The concentration of the analyzed substances was assessed by the internal standard method, which was rutin. To determine the concentration of luteolin, a standardized luteolin substance was used as a standard sample, the concentration of the remaining metabolites was estimated in terms of luteolin.Results and discussion. It was found that after oral administration of luteolin-7-glycoside in starch paste to laboratory animals, native luteolin-7-glycoside was not detected in blood plasma. The main metabolites were luteolin-diglucuronide and luteolin-glucuronide, their maximum plasma concentrations are about three times higher than luteolin and methyllyuteolin-diglucuronide. The results are compared with data from other studies.Conclusion. The absence of native luteolin-7-glycoside in blood plasma after oral administration makes it necessary to seriously reconsider the relevance of the conclusions obtained during studies of its activity in vitro. However, in the presence of antiviral activity in vivo, there is an urgent need
{"title":"Identification of luteolin-7-glucoside metabolites after oral administration and development of a method for their quantitative analysis","authors":"G. V. Adamov, O. L. Saybel, A. N. Babenko, E. S. Melnikov, A. I. Radimich, O. Kulyak, L. Krepkova","doi":"10.33380/2305-2066-2024-13-3-1767","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-3-1767","url":null,"abstract":"Introduction. The development and registration of antiviral drugs is an urgent task. Flavonoids, in particular, luteolin-7-glycoside (cinaroside, luteolin-7-O-glycoside) demonstrate high broad-spectrum antiviral activity in vitro, and the industrial regulations for the production of luteolin-7-glycoside from the leaves of holly willow have already been developed at the VILAR. One of the problems with the introduction of flavonoids into medical practice is their low bioavailability and intensive biotransformation. Existing publications provide contradictory data on the pharmacokinetics of luteolin-7-glycoside, and therefore our own research was conducted.Aim. To develop a methodology for the quantitative analysis of luteolin-7-glycoside and its metabolites in blood plasma and to test it on laboratory animals.Materials and methods. Animal experiments were carried out in accordance with the requirements of the \"Guidelines for conducting preclinical studies of medicines\". To develop a method of analysis and further clarify the time intervals of blood sampling, time points were analyzed: 30, 60 minutes, 2, 4, 8, 24 hours after administration of the test substance. Tubes with citrate blood of laboratory animals were centrifuged at 2000 rpm for 10 minutes. The plasma was placed in an Eppendorf-type test tube, frozen and stored at –20 °C until chromatographic analysis was performed. Blood plasma sample preparation was carried out by precipitation with methyl alcohol, the supernatant was chromatographically separated on a column Luna® 5 µm C18 column 100 Å 250 × 4.6 mm in a gradient mode in a water-acetonitrile system and a modifier – 0.2 % formic acid. The metabolites were identified by high-performance liquid chromatography with mass spectrometric detection. To do this, the spectral characteristics of the peaks that appeared on the chromatograms of blood plasma samples after oral administration of luteolin-7-glycoside were interpreted. The concentration of the analyzed substances was assessed by the internal standard method, which was rutin. To determine the concentration of luteolin, a standardized luteolin substance was used as a standard sample, the concentration of the remaining metabolites was estimated in terms of luteolin.Results and discussion. It was found that after oral administration of luteolin-7-glycoside in starch paste to laboratory animals, native luteolin-7-glycoside was not detected in blood plasma. The main metabolites were luteolin-diglucuronide and luteolin-glucuronide, their maximum plasma concentrations are about three times higher than luteolin and methyllyuteolin-diglucuronide. The results are compared with data from other studies.Conclusion. The absence of native luteolin-7-glycoside in blood plasma after oral administration makes it necessary to seriously reconsider the relevance of the conclusions obtained during studies of its activity in vitro. However, in the presence of antiviral activity in vivo, there is an urgent need","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"74 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141922368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.33380/2305-2066-2024-13-3-1749
M. Mandrik, I. A. Sadkovskii, E. D. Pinegina, L. A. Korol, I. I. Krasnuk
Introduction. Darunavir as an effective antiretroviral drug is widely used in clinical practice, including for the treatment of pediatric patients, as well as pregnant women, and for personalized therapy. Currently darunavir is used in the production of finished dosage forms, both in the form of crystalline ethanolate and in the form of an amorphous substance. In this regard, there is a need to develop and improve methods for the quantitative determination of darunavir. As an inexpensive and effective alternative to common chromatographic and titrimetric methods, spectrophotometric determination of darunavir in the ultraviolet region of the spectrum (UV spectrophotometry) may be used.Aim. To develop and validate a method for the quantitative determination of amorphous darunavir in the substance by UV spectrophotometry.Materials and methods. The following substances and consumables were used for the research: powdered amorphous darunavir substance (USP); darunavir reference standard (MSN Pharmachem Pvt. Ltd., India); methanol for HPLC Gradient Grade 99.9 % (High purity); acetonitrile for HPLC Gradient Grade 99.9 %; glacial acetic acid for HPLC; 0.1 M perchloric acid solution (in anhydrous acetic acid) for titration in non-aqueous media; nylon syringe filters with a pore diameter of 0.22 microns. Spectrophotometric determination of darunavir was carried out using an Cary 60 spectrophotometer (Agilent Technologies, USA) and a UNICO 2800 spectrophotometer (United Products & Instruments, Inc., USA). To prepare standard solutions, we used analytical balance Analytical Balance MS105/A (METTLER TOLEDO, Switzerland), analytical balance GH-120 (AND, Japan) class A measuring glassware, graduated pipettes ISOLAB.Results and discussion. The method was developed and validated for the following characteristics: specificity, linearity, accuracy, precision, analytical range. According to the study results, the main validation characteristics of the method meet the acceptance criteria.Conclusion. A new method for the quantitative determination of amorphous darunavir by UV spectrophotometry was successfully developed and validated. The method may be used to control the quality of substances of amorphous darunavir, including the intrapharmaceutical control.
{"title":"Development and validation of UV-spectrophotometry method for quantitative determination of amorphous darunavir","authors":"M. Mandrik, I. A. Sadkovskii, E. D. Pinegina, L. A. Korol, I. I. Krasnuk","doi":"10.33380/2305-2066-2024-13-3-1749","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-3-1749","url":null,"abstract":"Introduction. Darunavir as an effective antiretroviral drug is widely used in clinical practice, including for the treatment of pediatric patients, as well as pregnant women, and for personalized therapy. Currently darunavir is used in the production of finished dosage forms, both in the form of crystalline ethanolate and in the form of an amorphous substance. In this regard, there is a need to develop and improve methods for the quantitative determination of darunavir. As an inexpensive and effective alternative to common chromatographic and titrimetric methods, spectrophotometric determination of darunavir in the ultraviolet region of the spectrum (UV spectrophotometry) may be used.Aim. To develop and validate a method for the quantitative determination of amorphous darunavir in the substance by UV spectrophotometry.Materials and methods. The following substances and consumables were used for the research: powdered amorphous darunavir substance (USP); darunavir reference standard (MSN Pharmachem Pvt. Ltd., India); methanol for HPLC Gradient Grade 99.9 % (High purity); acetonitrile for HPLC Gradient Grade 99.9 %; glacial acetic acid for HPLC; 0.1 M perchloric acid solution (in anhydrous acetic acid) for titration in non-aqueous media; nylon syringe filters with a pore diameter of 0.22 microns. Spectrophotometric determination of darunavir was carried out using an Cary 60 spectrophotometer (Agilent Technologies, USA) and a UNICO 2800 spectrophotometer (United Products & Instruments, Inc., USA). To prepare standard solutions, we used analytical balance Analytical Balance MS105/A (METTLER TOLEDO, Switzerland), analytical balance GH-120 (AND, Japan) class A measuring glassware, graduated pipettes ISOLAB.Results and discussion. The method was developed and validated for the following characteristics: specificity, linearity, accuracy, precision, analytical range. According to the study results, the main validation characteristics of the method meet the acceptance criteria.Conclusion. A new method for the quantitative determination of amorphous darunavir by UV spectrophotometry was successfully developed and validated. The method may be used to control the quality of substances of amorphous darunavir, including the intrapharmaceutical control.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"5 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141921437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.33380/2305-2066-2024-13-3-1810
A. Savvateev, O. V. Fateenkova, A. V. Braun, V. L. Beloborodov, I. Gravel
Introduction. Determination of pesticide residues presence in herbal plants and preparations based on them is an important step in confirming safety at the stage of the quality control of herbal plants. The usage of organophosphate pesticides (OPs) for the purposes of treatment of medicinal plants in the growing process is increasing. Scientific sources provide information on the detection of OPs in herbal plants, including quantities exceeding the allowed percentage limits as it is settled in regulatory documentation. At the same time, the problem of the distribution of particular kinds of OPs in the organs of herbal plants and their persistence remains understudied.Aim. The present research aims to study the distribution in various parts of the herbal plants (marigolds, valerian, and stinging nettle) and the persistence of malathion and diazinon.Materials and methods. Stinging nettle, that grows everywhere, exclusively cultivated marigolds, and valerian were selected as model plants. All of the plants were divided into three equal groups. Young plant shoots were processed twice with "Aliot" products containing 570 g/l of malathion and "Terradox" containing 40 g/kg of diazinon. The first group of plants was processed with pesticides following the manufacturer's instructions. The second group was treated in quantities, that were three times higher than the recommended dosage. The third group (control), was not processed with pesticides. Samples of various parts of growing herbal plants were analyzed at certain time points with the HPLC-MS/MS method according to the developed methodology. In order to study the persistence, we carried out a repeated analysis of dried samples stored without access to sunlight 0.5 years after the first one according to the requirements of the State Pharmacopoeia of the Russian Federation XV.Results and discussion. The authors found malathion and diazinon in all of the analyzed parts of medicinal marigolds, in leaves and roots of nettle dioecious, in deciduous shoots and rhizomes with roots of valerian officinalis. The highest proportion of pesticides was discovered in underground plant organs. When processed according to the instructions, in marigold and nettle roots and in rhizomes with valerian roots 16.7 mg/kg, 4.5 mg/kg, and 1.7 mg/kg of malathion and 19.6 mg/kg, 4.1 mg/kg, and 1.5 mg/kg of diazinon were found, respectively. These quantities exceed the allowed limits. The quantity of pesticides in the flowers of medicinal marigolds does not exceed the permissible values. The research on the persistence of these OPs data demonstrates that malathion and diazinon persist in plant tissues for a long time.Conclusion. As a result of the research quantitative characteristics of the distribution of malathion and diazinon in various parts of medicinal marigolds, medicinal valerian, and dioecious nettle, as well as the rate and the extent of degradation of OPs during six months, were determined.
{"title":"Analysis of the distribution and persistence of organophosphorus pesticides malathion and diazinon in herbal plants","authors":"A. Savvateev, O. V. Fateenkova, A. V. Braun, V. L. Beloborodov, I. Gravel","doi":"10.33380/2305-2066-2024-13-3-1810","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-3-1810","url":null,"abstract":"Introduction. Determination of pesticide residues presence in herbal plants and preparations based on them is an important step in confirming safety at the stage of the quality control of herbal plants. The usage of organophosphate pesticides (OPs) for the purposes of treatment of medicinal plants in the growing process is increasing. Scientific sources provide information on the detection of OPs in herbal plants, including quantities exceeding the allowed percentage limits as it is settled in regulatory documentation. At the same time, the problem of the distribution of particular kinds of OPs in the organs of herbal plants and their persistence remains understudied.Aim. The present research aims to study the distribution in various parts of the herbal plants (marigolds, valerian, and stinging nettle) and the persistence of malathion and diazinon.Materials and methods. Stinging nettle, that grows everywhere, exclusively cultivated marigolds, and valerian were selected as model plants. All of the plants were divided into three equal groups. Young plant shoots were processed twice with \"Aliot\" products containing 570 g/l of malathion and \"Terradox\" containing 40 g/kg of diazinon. The first group of plants was processed with pesticides following the manufacturer's instructions. The second group was treated in quantities, that were three times higher than the recommended dosage. The third group (control), was not processed with pesticides. Samples of various parts of growing herbal plants were analyzed at certain time points with the HPLC-MS/MS method according to the developed methodology. In order to study the persistence, we carried out a repeated analysis of dried samples stored without access to sunlight 0.5 years after the first one according to the requirements of the State Pharmacopoeia of the Russian Federation XV.Results and discussion. The authors found malathion and diazinon in all of the analyzed parts of medicinal marigolds, in leaves and roots of nettle dioecious, in deciduous shoots and rhizomes with roots of valerian officinalis. The highest proportion of pesticides was discovered in underground plant organs. When processed according to the instructions, in marigold and nettle roots and in rhizomes with valerian roots 16.7 mg/kg, 4.5 mg/kg, and 1.7 mg/kg of malathion and 19.6 mg/kg, 4.1 mg/kg, and 1.5 mg/kg of diazinon were found, respectively. These quantities exceed the allowed limits. The quantity of pesticides in the flowers of medicinal marigolds does not exceed the permissible values. The research on the persistence of these OPs data demonstrates that malathion and diazinon persist in plant tissues for a long time.Conclusion. As a result of the research quantitative characteristics of the distribution of malathion and diazinon in various parts of medicinal marigolds, medicinal valerian, and dioecious nettle, as well as the rate and the extent of degradation of OPs during six months, were determined.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"30 27","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141659839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-10DOI: 10.33380/2305-2066-2024-13-3-1793
N. Melnikova, I. A. Sheferov, A. A. Emasheva, A. A. Sheferova, D. A. Panteleev, A. I. Slivkin
Introduction. The review considered the basic concepts of drug release and kinetic modeling of this process from dosage forms (DF) according to the dissolution profile using a vertical Franz diffusion cell.Text. Drug release from dosage forms (ointments, gels, transdermal patches and polymer films) is usually described as the processes of drug dissolution in the biological system. Formally, this process, in accordance with pharmacopoeial methods, is assessed using various solubility tests. The theoretical aspects of drug release are based on the theory of mass transfer of substances from a polymer matrix into a system that simulates a biological environment. Drug release can be carried out via the passive diffusion mechanism according to Fick and "non-Fick" diffusion, drug desorption from the inner side of the membrane, as well as other mechanisms. Drug release is determined both lipophilicity and the membrane nature, both various physicochemical parameters of the drug. One of the correlation characteristics of mass transfer is the assessment of the permeability coefficient for a specific membrane that simulates skin. Permeability coefficient describes the rate of penetration of a drug per unit concentration in distance/time units. An example of relationship of "structure-permeability" correlation are the equations relating the permeability constant and lipophilicity to the molecular weight of the drug. The paper showed statistical methods of data analysis (MANOVA, ANOVA) and model-dependent methods (zero order, first order, Higuchi model, Korsmeyer – Peppas model, Hixson – Crowell model, etc.). The ideal drug delivery of non-degradable and non-disaggregating drugs describes as drug release model by zero-order reaction. For drug release of water-soluble drugs from a porous matrix, first-order reaction model is more typical. Kinetic models of fractional power functions are used usually as the cube root law (Hixson – Crowell model) or the square root law (Higuchi model) to describe the process of drug release from gels and dermal films and patches. The Korsmeyer – Peppas model allows us to evaluate the mechanism of mass transfer with Fickian diffusion or another process.Conclusion. Mathematical modeling of the drug release kinetics from soft dosage forms is an important element for the development and optimization of their compositions. The study of the drugs release from soft dosage forms, including TTS and polymer films, as well as the release from solid dosage forms, is based on establishing correlations between the kinetics of the release and dissolution profile. The main release models, regardless of the DF, remain the following models: zero order, first order, Korsmeyer – Peppas, Higuchi, Hickson – Crowell, the empirical or semi-empirical constants of which vary significantly depending on the DF and the release mechanism (Fickian diffusion or another drug mass transfer mechanism). Correlation relationships QSPeR or QSPR, using the coefficient
{"title":"Evaluation of drug release from topical dosage forms and permeability prediction through the skin barrier (review)","authors":"N. Melnikova, I. A. Sheferov, A. A. Emasheva, A. A. Sheferova, D. A. Panteleev, A. I. Slivkin","doi":"10.33380/2305-2066-2024-13-3-1793","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-3-1793","url":null,"abstract":"Introduction. The review considered the basic concepts of drug release and kinetic modeling of this process from dosage forms (DF) according to the dissolution profile using a vertical Franz diffusion cell.Text. Drug release from dosage forms (ointments, gels, transdermal patches and polymer films) is usually described as the processes of drug dissolution in the biological system. Formally, this process, in accordance with pharmacopoeial methods, is assessed using various solubility tests. The theoretical aspects of drug release are based on the theory of mass transfer of substances from a polymer matrix into a system that simulates a biological environment. Drug release can be carried out via the passive diffusion mechanism according to Fick and \"non-Fick\" diffusion, drug desorption from the inner side of the membrane, as well as other mechanisms. Drug release is determined both lipophilicity and the membrane nature, both various physicochemical parameters of the drug. One of the correlation characteristics of mass transfer is the assessment of the permeability coefficient for a specific membrane that simulates skin. Permeability coefficient describes the rate of penetration of a drug per unit concentration in distance/time units. An example of relationship of \"structure-permeability\" correlation are the equations relating the permeability constant and lipophilicity to the molecular weight of the drug. The paper showed statistical methods of data analysis (MANOVA, ANOVA) and model-dependent methods (zero order, first order, Higuchi model, Korsmeyer – Peppas model, Hixson – Crowell model, etc.). The ideal drug delivery of non-degradable and non-disaggregating drugs describes as drug release model by zero-order reaction. For drug release of water-soluble drugs from a porous matrix, first-order reaction model is more typical. Kinetic models of fractional power functions are used usually as the cube root law (Hixson – Crowell model) or the square root law (Higuchi model) to describe the process of drug release from gels and dermal films and patches. The Korsmeyer – Peppas model allows us to evaluate the mechanism of mass transfer with Fickian diffusion or another process.Conclusion. Mathematical modeling of the drug release kinetics from soft dosage forms is an important element for the development and optimization of their compositions. The study of the drugs release from soft dosage forms, including TTS and polymer films, as well as the release from solid dosage forms, is based on establishing correlations between the kinetics of the release and dissolution profile. The main release models, regardless of the DF, remain the following models: zero order, first order, Korsmeyer – Peppas, Higuchi, Hickson – Crowell, the empirical or semi-empirical constants of which vary significantly depending on the DF and the release mechanism (Fickian diffusion or another drug mass transfer mechanism). Correlation relationships QSPeR or QSPR, using the coefficient","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"102 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141362544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.33380/2305-2066-2024-13-3-1823
S. D. Kulikova, М. B. Sokol, Z. M. Kozlova, P. A. Losenkova, P. Y. Parshinova, A. Poluyanov
Introduction. Biorelevant dissolution media reconstitute the composition of the contents of the gastrointestinal tract. They are used as dissolution media in the evaluation of dissolution profiles of different dosage forms. Simulated biological fluids allow prediction of in vivo test results. The development of the composition of simulated salivary fluid allows the evaluation of drug properties under physiologically relevant conditions.Aim. Evaluation of the release of the drug product "glycine, sublingual tablets, 100 mg", domestically produced in Simulated Saliva 5 pH 6.8.Materials and methods. The preparations used for analysis were: «Glycine, sublingual tablets, 100 mg», domestically produced with valid expiration date. Comparative dissolution kinetics test was carried out on the dissolution test apparatus DT 6 (ERWEKA GmbH, Germany). Chromatographic separation and detection were performed on a Waters W1525 Binary HPLC Pump high-performance liquid chromatograph (Waters Corporation, USA) equipped with column and sample thermostat, degasser, autosampler and Waters 2487 Dual Absorbance Detector (Waters Corporation, USA). Detection was performed at a wavelength of 254 ± 2 nm after derivatization of the glycine molecule with 4-toluenesulfonyl chloride. A Grace Platinum C18-EPS 5 μm 4.6 × 250 mm Grace Platinum C18-EPS 5 μm 4.6 × 250 mm column (Grace, USA) and a Grace Platinum C18-EPS 5 μm 4.6 × 250 mm pre-column (Grace, USA) were used. The following software was used for the study: validated Microsoft Excel spreadsheet for calculating glycine release values.Results and discussion. The technique for quantitative determination of glycine was developed and validated under CDKT in purified water medium and Simulated Saliva 5 pH 6.8. The validated analytical range of the methodology was 10–110 % of the nominal concentration of the dosage form in 300 mL volume of medium. The developed analytical technique was validated in the biopredictive in vitro test of glycine preparations. During the study in Simulated Saliva medium for drug formulations, more discriminative data were obtained, which were expressed as: different dissolution rate, curvature of the slope of the dissolution profile and time to reach the plateau in contrast to the dissolution medium purified water.Conclusion. The quantification technique was developed and validated for biopredictive tests of tablets "Glycine, sublingual tablets, 100 mg". The analytical range of the technique was 10–110 % of the nominal concentration of the dosage form in 300 mL volume of medium. The results of the test in artificial saliva medium were more discriminatory.
{"title":"A biorelevant test for tablets glycine sublingual in the «simulated saliva» dissolution medium","authors":"S. D. Kulikova, М. B. Sokol, Z. M. Kozlova, P. A. Losenkova, P. Y. Parshinova, A. Poluyanov","doi":"10.33380/2305-2066-2024-13-3-1823","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-3-1823","url":null,"abstract":"Introduction. Biorelevant dissolution media reconstitute the composition of the contents of the gastrointestinal tract. They are used as dissolution media in the evaluation of dissolution profiles of different dosage forms. Simulated biological fluids allow prediction of in vivo test results. The development of the composition of simulated salivary fluid allows the evaluation of drug properties under physiologically relevant conditions.Aim. Evaluation of the release of the drug product \"glycine, sublingual tablets, 100 mg\", domestically produced in Simulated Saliva 5 pH 6.8.Materials and methods. The preparations used for analysis were: «Glycine, sublingual tablets, 100 mg», domestically produced with valid expiration date. Comparative dissolution kinetics test was carried out on the dissolution test apparatus DT 6 (ERWEKA GmbH, Germany). Chromatographic separation and detection were performed on a Waters W1525 Binary HPLC Pump high-performance liquid chromatograph (Waters Corporation, USA) equipped with column and sample thermostat, degasser, autosampler and Waters 2487 Dual Absorbance Detector (Waters Corporation, USA). Detection was performed at a wavelength of 254 ± 2 nm after derivatization of the glycine molecule with 4-toluenesulfonyl chloride. A Grace Platinum C18-EPS 5 μm 4.6 × 250 mm Grace Platinum C18-EPS 5 μm 4.6 × 250 mm column (Grace, USA) and a Grace Platinum C18-EPS 5 μm 4.6 × 250 mm pre-column (Grace, USA) were used. The following software was used for the study: validated Microsoft Excel spreadsheet for calculating glycine release values.Results and discussion. The technique for quantitative determination of glycine was developed and validated under CDKT in purified water medium and Simulated Saliva 5 pH 6.8. The validated analytical range of the methodology was 10–110 % of the nominal concentration of the dosage form in 300 mL volume of medium. The developed analytical technique was validated in the biopredictive in vitro test of glycine preparations. During the study in Simulated Saliva medium for drug formulations, more discriminative data were obtained, which were expressed as: different dissolution rate, curvature of the slope of the dissolution profile and time to reach the plateau in contrast to the dissolution medium purified water.Conclusion. The quantification technique was developed and validated for biopredictive tests of tablets \"Glycine, sublingual tablets, 100 mg\". The analytical range of the technique was 10–110 % of the nominal concentration of the dosage form in 300 mL volume of medium. The results of the test in artificial saliva medium were more discriminatory.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141381846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.33380/2305-2066-2024-13-2-1772
V. Filatov, O. Kulyak, E. I. Kalenikova
Introduction. Despite the proven clinical efficacy of antifungal and anti-inflammatory drugs for the prevention and treatment of seborrheic dermatitis, the search for new targets and the development of new substances with a beneficial effect on the scalp microflora, with a low risk of antimicrobial resistance and adverse effects, are relevant.Aim. Development of the antimicrobial multicomponent pharmaceutical substance of plant origin in stages: from a literature search for promising substances, analysis of their composition by GC-MS, in silico evaluation of the affinity of individual components to pathogenetic targets, selection of the optimal composition of a multicomponent substance based on the results of in vitro research of antimicrobial action and the making of a medical dosage form based on it – a medicinal shampoo for the treatment of seborrheic dermatitis.Materials and methods. Objects of research: tea tree essential oil, 1,8-cineole, α-(-)-bisabolol and the multicomponent substance based on them. Methods: molecular docking (AutoDock version 4.2), prediction of pharmacological activity (Phyto4Health), TLC, GC-MS, study of antimicrobial activity in vitro.Results and discussion. Based on the results of a literature search, 3 promising substances were selected for the development of a multicomponent plant-based substance: tea tree essential oil, 1,8-cineole and α-(-)-bisabolol. Molecular docking predicted the targeted activity of the phytochemicals of tea tree essential oil, 1,8-cineole and α-(-)-bisabolol on the domains of ABC-transporters of microorganisms involved in the pathogenesis of seborrheic dermatitis and justified the possibility of use for therapy. The multicomponent substance has been developed based on tea tree essential oil, 1,8-cineole and α-(-)-bisabolol in a mass ratio of 1 : 1 : 1. The qualitative composition of the substance was assessed by TLC and GC-MS methods, and 15 terpenes were quantitatively identified in its composition with a predominance of terpinen-4-ol (16.98 %), 1,8-cineole (25.63 %) and α-(-)-bisabolol (27.67 %). The synergistic antimicrobial activity of the substance has been established against S. epidermidis, S. aureus, C. albicans and M. furfur in comparison with benzalkonium chloride, ketoconazole and climbazole. The composition of a new medical shampoo based on the investigated substance has been developed, which has a pronounced antifungal effect (more than 99.0 %) against M. furfur without visible suppression of normal microflora. For the novel substance of plant origin and medical shampoo, quality parameters were assessed in accordance with the Russian Pharmacopoeia of XIV edition.Conclusion. A substance of plant origin with synergistic and targeted antimicrobial activity has been developed. It has an interest for further study as a drug and API for new products for the treatment of seborrheic dermatitis.
{"title":"Algorithm for the development of a multicomponent pharmaceutical substance of plant origin with antimicrobial action: from science search to dosage form","authors":"V. Filatov, O. Kulyak, E. I. Kalenikova","doi":"10.33380/2305-2066-2024-13-2-1772","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-2-1772","url":null,"abstract":"Introduction. Despite the proven clinical efficacy of antifungal and anti-inflammatory drugs for the prevention and treatment of seborrheic dermatitis, the search for new targets and the development of new substances with a beneficial effect on the scalp microflora, with a low risk of antimicrobial resistance and adverse effects, are relevant.Aim. Development of the antimicrobial multicomponent pharmaceutical substance of plant origin in stages: from a literature search for promising substances, analysis of their composition by GC-MS, in silico evaluation of the affinity of individual components to pathogenetic targets, selection of the optimal composition of a multicomponent substance based on the results of in vitro research of antimicrobial action and the making of a medical dosage form based on it – a medicinal shampoo for the treatment of seborrheic dermatitis.Materials and methods. Objects of research: tea tree essential oil, 1,8-cineole, α-(-)-bisabolol and the multicomponent substance based on them. Methods: molecular docking (AutoDock version 4.2), prediction of pharmacological activity (Phyto4Health), TLC, GC-MS, study of antimicrobial activity in vitro.Results and discussion. Based on the results of a literature search, 3 promising substances were selected for the development of a multicomponent plant-based substance: tea tree essential oil, 1,8-cineole and α-(-)-bisabolol. Molecular docking predicted the targeted activity of the phytochemicals of tea tree essential oil, 1,8-cineole and α-(-)-bisabolol on the domains of ABC-transporters of microorganisms involved in the pathogenesis of seborrheic dermatitis and justified the possibility of use for therapy. The multicomponent substance has been developed based on tea tree essential oil, 1,8-cineole and α-(-)-bisabolol in a mass ratio of 1 : 1 : 1. The qualitative composition of the substance was assessed by TLC and GC-MS methods, and 15 terpenes were quantitatively identified in its composition with a predominance of terpinen-4-ol (16.98 %), 1,8-cineole (25.63 %) and α-(-)-bisabolol (27.67 %). The synergistic antimicrobial activity of the substance has been established against S. epidermidis, S. aureus, C. albicans and M. furfur in comparison with benzalkonium chloride, ketoconazole and climbazole. The composition of a new medical shampoo based on the investigated substance has been developed, which has a pronounced antifungal effect (more than 99.0 %) against M. furfur without visible suppression of normal microflora. For the novel substance of plant origin and medical shampoo, quality parameters were assessed in accordance with the Russian Pharmacopoeia of XIV edition.Conclusion. A substance of plant origin with synergistic and targeted antimicrobial activity has been developed. It has an interest for further study as a drug and API for new products for the treatment of seborrheic dermatitis.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"7 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141101254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.33380/2305-2066-2024-13-2-1724
A. V. Zykova, S. Krivoshchekov, D. A. Isakov, A. M. Guryev, M. V. Belousov
Introduction. The widespread use of heparin preparations for the treatment and prevention of venous thromboembolic complications is known. One of the low molecular weight heparin drugs successfully used in clinical practice is calcium nadroparin. The modern approach to assessing the quality of medicines involves the use of standards, in comparison with which the quality control of the drug is carried out – standard samples (SS). The most important specific parameter in assessing the authenticity of low molecular weight heparins is the characteristic of the fractional composition.Aim. The aim of the work was to develop, attestation and determine the stability during the shelf life of a secondary standard sample to determine the authenticity of calcium nadroparin as part of improving the quality control system of the enterprise with the prospect of creating a domestic pharmacopoeia standard sample.Materials and methods. The object of development and attestation was the standard sample of the enterprise – low molecular weight heparin, obtained on the basis of the Technology implementation center of Siberian state medical university. The certified standard sample was obtained by purification of calcium nadroparin by solid-phase extraction. The completeness of the purification was confirmed by comparing the chromatograms of the purified samples with the chromatograms of the international standard sample. The characteristics of the molecular weight distribution were determined chromatographically. The stability of the certified SSE (the standard sample of the enterprise) was studied under two storage conditions – at a temperature below 8 °C in a dry state for 16 months and in solution at –40 °C for 6 months by evaluating trends in molecular weight distribution.Results and discussion. For each batch of the certified standard sample, the molecular weight and molecular weight characteristics are calculated in 2 parallel definitions, and a representative chromatogram is presented. The values of the relative standard deviation of the molecular weight of the samples and the content of the controlled fractions did not exceed 2.5 %. A detailed analysis of the molecular weight distribution showed the "classical" dependence of RSD (relative standard deviation) from the average value with a significant increase up to 30 % for small fraction values (less than 0.5 %). It was found that during 16 months at a storage temperature below 8 ºC, the molecular weight and molecular weight characteristics of standard samples of low molecular weight heparin did not significantly change. However, in the SSE solution at a storage temperature of minus 40 °C for 6 months, they degraded by more than 10 %.Conclusion. According to the results of the study, a protocol has been developed for obtaining a standard sample of low-molecular-weight heparin for the standardization of the calcium nadroparin substance according to the indicator "molecular weight distribution". The established
{"title":"Development and attestation of a standard sample of calcium nadroparin","authors":"A. V. Zykova, S. Krivoshchekov, D. A. Isakov, A. M. Guryev, M. V. Belousov","doi":"10.33380/2305-2066-2024-13-2-1724","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-2-1724","url":null,"abstract":"Introduction. The widespread use of heparin preparations for the treatment and prevention of venous thromboembolic complications is known. One of the low molecular weight heparin drugs successfully used in clinical practice is calcium nadroparin. The modern approach to assessing the quality of medicines involves the use of standards, in comparison with which the quality control of the drug is carried out – standard samples (SS). The most important specific parameter in assessing the authenticity of low molecular weight heparins is the characteristic of the fractional composition.Aim. The aim of the work was to develop, attestation and determine the stability during the shelf life of a secondary standard sample to determine the authenticity of calcium nadroparin as part of improving the quality control system of the enterprise with the prospect of creating a domestic pharmacopoeia standard sample.Materials and methods. The object of development and attestation was the standard sample of the enterprise – low molecular weight heparin, obtained on the basis of the Technology implementation center of Siberian state medical university. The certified standard sample was obtained by purification of calcium nadroparin by solid-phase extraction. The completeness of the purification was confirmed by comparing the chromatograms of the purified samples with the chromatograms of the international standard sample. The characteristics of the molecular weight distribution were determined chromatographically. The stability of the certified SSE (the standard sample of the enterprise) was studied under two storage conditions – at a temperature below 8 °C in a dry state for 16 months and in solution at –40 °C for 6 months by evaluating trends in molecular weight distribution.Results and discussion. For each batch of the certified standard sample, the molecular weight and molecular weight characteristics are calculated in 2 parallel definitions, and a representative chromatogram is presented. The values of the relative standard deviation of the molecular weight of the samples and the content of the controlled fractions did not exceed 2.5 %. A detailed analysis of the molecular weight distribution showed the \"classical\" dependence of RSD (relative standard deviation) from the average value with a significant increase up to 30 % for small fraction values (less than 0.5 %). It was found that during 16 months at a storage temperature below 8 ºC, the molecular weight and molecular weight characteristics of standard samples of low molecular weight heparin did not significantly change. However, in the SSE solution at a storage temperature of minus 40 °C for 6 months, they degraded by more than 10 %.Conclusion. According to the results of the study, a protocol has been developed for obtaining a standard sample of low-molecular-weight heparin for the standardization of the calcium nadroparin substance according to the indicator \"molecular weight distribution\". The established ","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"11 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141100530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.33380/2305-2066-2024-13-2-1765
M. Povydysh, M. U. Goncharov
Introduction. The State Pharmacopoeia of the Russian Federation, XIV-th edition (SP XIV), includes 107 monographs devoted to medicinal plant materials. The purpose of the study was to identify incorrect Latin names of medicinal plants in the monographs of the XIV edition, study the officially accepted Latin names and taxonomic position of medicinal plants in accordance with the contemporary system of flowering plants, and justify the need to make changes in subsequent editions of the pharmacopoeia.Text. 44 cases of incorrect Latin names were found. This is explained by the fact that when developing new pharmacopoeia monographs, either Latin names historically established in Russian pharmacognosy were used, or names that were legal at the time of the last edition of the Pharmacopoeia. The bulk of nomenclatural changes are associated with the adoption of the new APG system of flowering plants, based on molecular genetic data. The paper contains lists of plants for which the State Pharmacopoeia XIV contains an incorrect name of the genus, species, family or author, indicating the correct name, as well as comments on the rules of modern botanical nomenclature.Conclusion. In connection with the prospects for processing monographs on medicinal plant raw materials for the State Pharmacopoeia XV-th edition, as well as the EAEU Pharmacopoeia, the harmonization of the nomenclature of pharmacopoeial plants with modern international requirements becomes especially relevant.
简介俄罗斯联邦国家药典》第 XIV 版（SP XIV）包括 107 篇药用植物材料专论。研究的目的是找出第 XIV 版专著中错误的药用植物拉丁名，研究官方认可的药用植物拉丁名以及根据当代开花植物系统划分的药用植物分类学位置，并证明有必要在后续版本的药典中进行修改。发现 44 例拉丁名不正确的情况。这是因为在编写新的药典专著时，要么使用了俄罗斯药物学历史上确定的拉丁名，要么使用了上一版药典时的合法名称。大部分名称的变化与采用基于分子遗传数据的开花植物新 APG 系统有关。本文列出了《国家药典》第 XIV 版中包含错误的属、种、科或作者名称的植物清单，并指出了正确的名称，还对现代植物命名规则进行了评论。鉴于为《国家药典》第 XV 版和《欧洲经济联盟药典》编写药用植物原料专著的前景，药 典植物命名法与现代国际要求的协调变得尤为重要。
{"title":"Outdated latin names of medicinal plants in the monographs of the State Pharmacopoeia of the Russian Federation, XIV edition (review)","authors":"M. Povydysh, M. U. Goncharov","doi":"10.33380/2305-2066-2024-13-2-1765","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-2-1765","url":null,"abstract":"Introduction. The State Pharmacopoeia of the Russian Federation, XIV-th edition (SP XIV), includes 107 monographs devoted to medicinal plant materials. The purpose of the study was to identify incorrect Latin names of medicinal plants in the monographs of the XIV edition, study the officially accepted Latin names and taxonomic position of medicinal plants in accordance with the contemporary system of flowering plants, and justify the need to make changes in subsequent editions of the pharmacopoeia.Text. 44 cases of incorrect Latin names were found. This is explained by the fact that when developing new pharmacopoeia monographs, either Latin names historically established in Russian pharmacognosy were used, or names that were legal at the time of the last edition of the Pharmacopoeia. The bulk of nomenclatural changes are associated with the adoption of the new APG system of flowering plants, based on molecular genetic data. The paper contains lists of plants for which the State Pharmacopoeia XIV contains an incorrect name of the genus, species, family or author, indicating the correct name, as well as comments on the rules of modern botanical nomenclature.Conclusion. In connection with the prospects for processing monographs on medicinal plant raw materials for the State Pharmacopoeia XV-th edition, as well as the EAEU Pharmacopoeia, the harmonization of the nomenclature of pharmacopoeial plants with modern international requirements becomes especially relevant.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141100259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-17DOI: 10.33380/2305-2066-2024-13-2-1677
R. Farkhutdinov, K. A. Pupykina, L. A. Sharafutdinova, A. M. Fedorova, Z. R. Hismatullina, M. Garipova, E. F. Koroleva, A. Yamaleeva, T. Rendyuk
Introduction. The development of new effective and safe herbal medicines capable of having a positive effect on reproductive status is an urgent task of domestic pharmacy. Medicinal plants are considered as alternative therapies aimed at increasing testosterone levels and fertility in men. The arsenal of medicinal plants used in traditional medicine for the treatment of diseases in men is mainly represented by phytoadaptogens, most of which have a small resource potential in Russia, therefore, it is relevant to search for plants with a sufficient raw material base and with the potential for cultivation. Thlaspi arvense L. is a promising medicinal plant, as it is widely used in folk medicine as a diuretic, anti-inflammatory, diaphoretic, antihistamine, hemostatic, astringent, has a positive effect on the processes of spermatogenesis and is widely distributed in our country. However, information on the chemical composition and biological activity of Thlaspi arvense L. they are insufficient, which shows the relevance of its further more detailed study in order to substantiate the possibility of application in practical medicine and solutions to the issues of standardization of medicinal plant raw materials.Aim. The study of the influence of Thlaspi arvense L. on the characteristics of the reproductive system of male rats.Materials and methods. The object of the study was an infusion of herbа Thlaspi arvense L. The features of the reproductive behavior of male rats after 21-day administration of the infusion of grass yarutka field were studied using tests that allow quantifying the severity of sexual motivation and sexual activity of males. The viability of spermatozoa in the ejaculate of rats was assessed, the total number of spermatozoa (ACS, million), degenerative and immobile forms (%) was calculated. Morphophysiological parameters of spermatogenesis of rats of control and experimental groups of animals were studied using classical histological methods. The concentration of testosterone in the blood serum of experimental groups of animals was determined by the enzyme immunoassay.Results and discussion. The results obtained allow us to conclude that the fertility of rats has increased against the background of the course administration of the infusion of herbа Thlaspi arvense L., as evidenced by an increase in the testosterone content in the blood, improvement of spermogram indicators and morphophysiological characteristics of spermatogenesis in the testicles of rats. The use of the infusion of herbа Thlaspi arvense L. has a protective effect on spermatogenesis. An increase in the thickness of the spermatogenic epithelium, the diameter of the cross-section of the convoluted seminal tubules and the index of spermatogenesis compared with the control group of animals was revealed. The positive effect of Thlaspi arvense L. on indicators of sexual motivation and sexual activity of male rats is shown.Conclusion. Thlaspi arvense L. is a promising medicin
{"title":"The study of the influence of Thlaspi arvense L. on the characteristics of the reproductive system of male rats","authors":"R. Farkhutdinov, K. A. Pupykina, L. A. Sharafutdinova, A. M. Fedorova, Z. R. Hismatullina, M. Garipova, E. F. Koroleva, A. Yamaleeva, T. Rendyuk","doi":"10.33380/2305-2066-2024-13-2-1677","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-2-1677","url":null,"abstract":"Introduction. The development of new effective and safe herbal medicines capable of having a positive effect on reproductive status is an urgent task of domestic pharmacy. Medicinal plants are considered as alternative therapies aimed at increasing testosterone levels and fertility in men. The arsenal of medicinal plants used in traditional medicine for the treatment of diseases in men is mainly represented by phytoadaptogens, most of which have a small resource potential in Russia, therefore, it is relevant to search for plants with a sufficient raw material base and with the potential for cultivation. Thlaspi arvense L. is a promising medicinal plant, as it is widely used in folk medicine as a diuretic, anti-inflammatory, diaphoretic, antihistamine, hemostatic, astringent, has a positive effect on the processes of spermatogenesis and is widely distributed in our country. However, information on the chemical composition and biological activity of Thlaspi arvense L. they are insufficient, which shows the relevance of its further more detailed study in order to substantiate the possibility of application in practical medicine and solutions to the issues of standardization of medicinal plant raw materials.Aim. The study of the influence of Thlaspi arvense L. on the characteristics of the reproductive system of male rats.Materials and methods. The object of the study was an infusion of herbа Thlaspi arvense L. The features of the reproductive behavior of male rats after 21-day administration of the infusion of grass yarutka field were studied using tests that allow quantifying the severity of sexual motivation and sexual activity of males. The viability of spermatozoa in the ejaculate of rats was assessed, the total number of spermatozoa (ACS, million), degenerative and immobile forms (%) was calculated. Morphophysiological parameters of spermatogenesis of rats of control and experimental groups of animals were studied using classical histological methods. The concentration of testosterone in the blood serum of experimental groups of animals was determined by the enzyme immunoassay.Results and discussion. The results obtained allow us to conclude that the fertility of rats has increased against the background of the course administration of the infusion of herbа Thlaspi arvense L., as evidenced by an increase in the testosterone content in the blood, improvement of spermogram indicators and morphophysiological characteristics of spermatogenesis in the testicles of rats. The use of the infusion of herbа Thlaspi arvense L. has a protective effect on spermatogenesis. An increase in the thickness of the spermatogenic epithelium, the diameter of the cross-section of the convoluted seminal tubules and the index of spermatogenesis compared with the control group of animals was revealed. The positive effect of Thlaspi arvense L. on indicators of sexual motivation and sexual activity of male rats is shown.Conclusion. Thlaspi arvense L. is a promising medicin","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"10 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140965334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-17DOI: 10.33380/2305-2066-2024-13-2-1786
E. Sanarova, A. Lantsova, L. Nikolaeva, N. Oborotova, L. M. Borisova
Introduction. Improving the efficacy of chemotherapy is a non-trivial task of modern oncology. Its successful solution requires knowledge in many fields, including physiology, pathology, clinical oncology, pharmacology and others. The search for small molecules that selectively kill tumor cells led to the accidental discovery of erastin.Text. Erastin is a unique molecule that has a quinazoline fragment in its structure. Not so long ago it became known that the antitumour effect of this compound is due to the induction of ferroptosis – an iron-dependent form of cell death caused by lipid peroxidation. Erastin is able to induce ferroptosis through various biochemical pathways, including blocking of cystine-glutamate transport channel of cell membrane and potential-dependent anion channel of mitochondria, as well as activation of p53 protein.Conclusion. Pharmacological induction of ferroptosis by erastin and its analogues represents a promising direction in cancer chemotherapy. In addition, erastin and its analogues are able to increase sensitivity to chemotherapy and radiation therapy, which allows us to talk about the possibility of their use in the combined treatment of malignant neoplasms.
{"title":"Ferroptosis inducers – erastin and analogues (review)","authors":"E. Sanarova, A. Lantsova, L. Nikolaeva, N. Oborotova, L. M. Borisova","doi":"10.33380/2305-2066-2024-13-2-1786","DOIUrl":"https://doi.org/10.33380/2305-2066-2024-13-2-1786","url":null,"abstract":"Introduction. Improving the efficacy of chemotherapy is a non-trivial task of modern oncology. Its successful solution requires knowledge in many fields, including physiology, pathology, clinical oncology, pharmacology and others. The search for small molecules that selectively kill tumor cells led to the accidental discovery of erastin.Text. Erastin is a unique molecule that has a quinazoline fragment in its structure. Not so long ago it became known that the antitumour effect of this compound is due to the induction of ferroptosis – an iron-dependent form of cell death caused by lipid peroxidation. Erastin is able to induce ferroptosis through various biochemical pathways, including blocking of cystine-glutamate transport channel of cell membrane and potential-dependent anion channel of mitochondria, as well as activation of p53 protein.Conclusion. Pharmacological induction of ferroptosis by erastin and its analogues represents a promising direction in cancer chemotherapy. In addition, erastin and its analogues are able to increase sensitivity to chemotherapy and radiation therapy, which allows us to talk about the possibility of their use in the combined treatment of malignant neoplasms.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"75 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140964626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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