Pub Date : 2023-10-20DOI: 10.33380/2305-2066-2023-12-4-1578
A. Kadyrbay, Z. B. Sakipova, N. A. Krishtanova, L. N. Ibragimova, M. B. Ibrayeva, A. E. Sakipov, E. N. Bekbolatova, Ch. Ridvanov, O. V. Sermukhamedova, Y. Adilbek, T. Y. Seiduali, A. K. Anartayeva, A. U. Kazim
Introduction. Choosing the optimal method for drying medicinal plants is an important aspect of obtaining herbal materials of pharmacopoeial quality. At the site of the pharmaceutical enterprise Fitoleum LLP (Esik, Kazakhstan), a technology for obtaining herbal materials from autumn wormwood ( Artemisia serotina Bunge) was developed, within the framework of which the optimal drying method was studied using IR radiation, convective drying and shadow drying in natural conditions. In parallel with the experimental approach, a method for simulating drying conditions was implemented. The development of technology for the obtaining of herbal materials is implemented using the "Quality by Design" concept, one of the principles of which is the modeling of experiments (Design of experiments, DoE). The advantage of modeling when studying the processes is that this technique allows you to simultaneously analyze several input parameters and their impact on quality indicators, while significantly reducing the number of experiments. Aim. To choose the optimal method for drying autumn wormwood herb for further production of herbal medicine or herbal materials. Materials and methods. During the experiment, the following equipment was used: a manual harvester for collecting plants, pallets or racks with a mesh bottom, infrared substrates, a convective drying oven, racks with pallets under a canopy in natural conditions, a grass cutter, vibrating sieves. Also, the study was carried out in accordance with the principles of the "Quality by Design" concept using the Minitab Statistical Software 21 program, using a statistical tool – Design of experiments (DoE). Results and discussion. The results of studies of various drying methods have shown that the most optimal is drying with IR radiation, which allows to maintain the content of essential oils (the main group of biologically active substances) at the optimal level – about 1,7 % with a raw material moisture content of no more than 13 %. The data obtained by simulating the experiment in the Minitab program were comparable to the results of the classical experimental design. The optimal method and technological parameters for drying autumn wormwood have been established – the use of IR radiation, temperature of 35–45 °C and drying time of 14–17 hours. Comparable data on the studied technological parameters of three sequentially produced series were obtained and the validity of the technological process for drying autumn wormwood was confirmed. Conclusion. Comparative analysis of the methods of drying medicinal plants – IR radiation, convective and shadow drying in natural conditions – of autumn wormwood ( Artemisia serotina Bunge) was carried out. It has been established that the maximum content of essential oils (as the main group of biologically active substances) in raw materials is observed when using drying using IR radiation at a temperature of 35–45 °C for 14– 17 hours. At the same time, the residual moisture
{"title":"Development of Optimal Technology for Drying Herbal Medicinal Raw Materials from Autumn Wormwood (<i>Artemisia serotina</i> Bunge) Based on Comparative Analysis","authors":"A. Kadyrbay, Z. B. Sakipova, N. A. Krishtanova, L. N. Ibragimova, M. B. Ibrayeva, A. E. Sakipov, E. N. Bekbolatova, Ch. Ridvanov, O. V. Sermukhamedova, Y. Adilbek, T. Y. Seiduali, A. K. Anartayeva, A. U. Kazim","doi":"10.33380/2305-2066-2023-12-4-1578","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1578","url":null,"abstract":"Introduction. Choosing the optimal method for drying medicinal plants is an important aspect of obtaining herbal materials of pharmacopoeial quality. At the site of the pharmaceutical enterprise Fitoleum LLP (Esik, Kazakhstan), a technology for obtaining herbal materials from autumn wormwood ( Artemisia serotina Bunge) was developed, within the framework of which the optimal drying method was studied using IR radiation, convective drying and shadow drying in natural conditions. In parallel with the experimental approach, a method for simulating drying conditions was implemented. The development of technology for the obtaining of herbal materials is implemented using the \"Quality by Design\" concept, one of the principles of which is the modeling of experiments (Design of experiments, DoE). The advantage of modeling when studying the processes is that this technique allows you to simultaneously analyze several input parameters and their impact on quality indicators, while significantly reducing the number of experiments. Aim. To choose the optimal method for drying autumn wormwood herb for further production of herbal medicine or herbal materials. Materials and methods. During the experiment, the following equipment was used: a manual harvester for collecting plants, pallets or racks with a mesh bottom, infrared substrates, a convective drying oven, racks with pallets under a canopy in natural conditions, a grass cutter, vibrating sieves. Also, the study was carried out in accordance with the principles of the \"Quality by Design\" concept using the Minitab Statistical Software 21 program, using a statistical tool – Design of experiments (DoE). Results and discussion. The results of studies of various drying methods have shown that the most optimal is drying with IR radiation, which allows to maintain the content of essential oils (the main group of biologically active substances) at the optimal level – about 1,7 % with a raw material moisture content of no more than 13 %. The data obtained by simulating the experiment in the Minitab program were comparable to the results of the classical experimental design. The optimal method and technological parameters for drying autumn wormwood have been established – the use of IR radiation, temperature of 35–45 °C and drying time of 14–17 hours. Comparable data on the studied technological parameters of three sequentially produced series were obtained and the validity of the technological process for drying autumn wormwood was confirmed. Conclusion. Comparative analysis of the methods of drying medicinal plants – IR radiation, convective and shadow drying in natural conditions – of autumn wormwood ( Artemisia serotina Bunge) was carried out. It has been established that the maximum content of essential oils (as the main group of biologically active substances) in raw materials is observed when using drying using IR radiation at a temperature of 35–45 °C for 14– 17 hours. At the same time, the residual moisture","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135569354","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 : 2023-10-12DOI: 10.33380/2305-2066-2023-12-4-1587
A. K. Whaley, R. I. Lukashov, A. O. Whaley, E. V. Zhokhova, N. S. Gurina, M. U. Goncharov, G. P. Yakovlev, V. A. Tsiarletskaya
Introduction. The genus Impatiens L. includes about 850 species, which are found mainly in tropical and subtropical climate zones. The Indigenous people of Pakistan used pastes and extracts from I. glandulifera for the treatment of joint pain, anxiety and skin allergies [6]. Flowers of I. glandulifera are used in Bach flower remedies, which are used for sedation, relaxation and helping to balance emotional states. Aim. Isolation and structural elucidation of 11 phenolic constituents from the aerial parts of I. glandulifera and the evaluation of their antioxidant activity. Materials and methods. The aerial part of Impatiens glandulifera Royle was collected in the Leningrad region near the village of Orekhovo in 2021. Fractions were analyzed by analytical high performance liquid chromatography (HPLC) using a Prominence LC-20 (Shimadzu, Japan) equipped with a diode array detector. The isolation of individual compounds was carried out by column chromatography on open glass columns with sorbents of different selectivity, as well as by preparative HPLC using a Smartlina (Knauer, Germany) equipped with a spectrophotometric detector. The structure of isolated individual compounds was established by 1D and 2D NMR spectroscopy (Bruker Avance III 400 MHz, Germany). To study the antioxidant activity, we used solutions obtained by dissolving the isolated substances in a mixture of dimethyl sulfoxide and ethanol; an aqueous solution of vitamin C and an alcoholic solution of Trolox (Sigma-Aldrich, Japan). Result and discussion. Phytochemical analysis of the aerial parts of Impatiens glandulifera Royle. resulted in the isolation of 11 polyphenolic secondary metabolites ( 1-11 ) and their structures were elucidated. The antioxidant activity of all isolated compounds was evaluated. Conclusion. The maximum RAP values of eriodyctiol ( 3 ), kaempferol ( 1 ), and quercetin ( 2 ) did not differ significantly ( p = 0.585) from those of the comparator preparations: vitamin C and Trolox, which indicates that the antioxidant effect of these three isolated compounds is comparable to the well-known antioxidants. However, the semi-effective concentrations of these substances are two or more times lower ( p = 2.56 · 10 –4 ) comparted with vitamin C.
{"title":"Flavonoids from <i>Impatiens grandulifera</i> and Their Antioxidant Activity","authors":"A. K. Whaley, R. I. Lukashov, A. O. Whaley, E. V. Zhokhova, N. S. Gurina, M. U. Goncharov, G. P. Yakovlev, V. A. Tsiarletskaya","doi":"10.33380/2305-2066-2023-12-4-1587","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1587","url":null,"abstract":"Introduction. The genus Impatiens L. includes about 850 species, which are found mainly in tropical and subtropical climate zones. The Indigenous people of Pakistan used pastes and extracts from I. glandulifera for the treatment of joint pain, anxiety and skin allergies [6]. Flowers of I. glandulifera are used in Bach flower remedies, which are used for sedation, relaxation and helping to balance emotional states. Aim. Isolation and structural elucidation of 11 phenolic constituents from the aerial parts of I. glandulifera and the evaluation of their antioxidant activity. Materials and methods. The aerial part of Impatiens glandulifera Royle was collected in the Leningrad region near the village of Orekhovo in 2021. Fractions were analyzed by analytical high performance liquid chromatography (HPLC) using a Prominence LC-20 (Shimadzu, Japan) equipped with a diode array detector. The isolation of individual compounds was carried out by column chromatography on open glass columns with sorbents of different selectivity, as well as by preparative HPLC using a Smartlina (Knauer, Germany) equipped with a spectrophotometric detector. The structure of isolated individual compounds was established by 1D and 2D NMR spectroscopy (Bruker Avance III 400 MHz, Germany). To study the antioxidant activity, we used solutions obtained by dissolving the isolated substances in a mixture of dimethyl sulfoxide and ethanol; an aqueous solution of vitamin C and an alcoholic solution of Trolox (Sigma-Aldrich, Japan). Result and discussion. Phytochemical analysis of the aerial parts of Impatiens glandulifera Royle. resulted in the isolation of 11 polyphenolic secondary metabolites ( 1-11 ) and their structures were elucidated. The antioxidant activity of all isolated compounds was evaluated. Conclusion. The maximum RAP values of eriodyctiol ( 3 ), kaempferol ( 1 ), and quercetin ( 2 ) did not differ significantly ( p = 0.585) from those of the comparator preparations: vitamin C and Trolox, which indicates that the antioxidant effect of these three isolated compounds is comparable to the well-known antioxidants. However, the semi-effective concentrations of these substances are two or more times lower ( p = 2.56 · 10 –4 ) comparted with vitamin C.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136013338","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 : 2023-10-12DOI: 10.33380/2305-2066-2023-12-4-1584
E. Yu. Zavarina, E. K. Krasova, I. A. Titovich, A. N. Kimaev
Introduction. Cerebrovascular diseases (CVD) are one of the most pressing medical and social problems due to the high rate of mortality and disability. Stroke is the leading cause of CVD. About 15 million strokes are registered annually in the world according to the World Federation of Neurological Societies. It should be noted that CVD of ischemic origin has a tendency to rejuvenation and growth. Traditionally, in clinical practice, antihypoxic, antioxidant agents, as well as drugs with neuroprotective and neurorehabilitation effects are used to treat CVD. In connection with the increase in the incidence of CVD, there is an urgent need to search for promising neuroprotectors. Aim. To study the neuroprotective activity of 5-ethoxy-2-ethylthiobenzimidazole (etomerzol) and 2-ethylthiobenzimidazole (bemityl) in a model of middle cerebral artery occlusion. Materials and methods. Occlusion of the middle cerebral artery (ОMCA) was used as a model. The object of the study was inbred male rats of the Dark Agouti line, randomized into five groups: a group of intact animals and four groups with OSMA: a control group, a group with the introduction of 5-ethoxy-2-ethylthiobenzimidazole (etomerzole, 25 mg/kg), a group with the introduction 2-ethylthiobenzimidazole (bemityl, 25 mg/kg) and a group with the reference drug dimethyl fumarate (DMF, 100 mg/kg). On the 1st, 3rd, and 7th days after the operation, the "Limb Stimulation" (SC) test was performed. On the 7th day, the tests "Open field" (OP) and "Elevated plus maze" (EPM) were performed. Euthanasia was performed on the 7th day in an induction chamber (Bioscape GmbH, CO 2 box for euthanasia, Germany). Results and discussion. The study showed a pronounced pharmacological effect of etomerzole in a model of acute ischemic stroke. The introduction of bemitil, etomerzol and DMF significantly reduced the neurological deficit 24 hours after OSMA and improved the psycho-functional state on the 7th day. Thus, in the etomerzol group on the first day after surgery, the neurological deficit was reduced by 1.9 times ( p < 0.05), and by 3 and 2.0 times ( p < 0.05) compared with the control group. While bemityl and DMF reduced the index by 1.3 ( p < 0.05) and 1.4 times ( p < 0.05) on the 3rd day and by 1.5 times ( p < 0.05) on the 7th day. In the OP test in the etomerzol group, an increase in HDA by 2.7 times ( p < 0.05) was observed compared with the control. The rate of peering into minks in the etomersol and bemitil groups was higher than in the control group by 2.6 ( p < 0.05) and 3.4 times ( p < 0.05), respectively. Search and research activity was increased in the same groups by 2.0 ( p < 0.05) and 2.2 times ( p < 0.05) compared to control animals. In the PCL test, the etomerzol and DMF groups showed an increase in the number of uprights in the sleeves compared to the control group by 2.7 ( p < 0.05) and 3.8 times ( p < 0.05), respectively. In the etomerzol and bemityl groups, there was an increase in the number of o
{"title":"Neuroprotective Activity of 5-ethoxy-2-ethylthiobenzimidazole (Etomerzol) and 2-ethylthiobenzimidazole (Bemitil) in a Model of Middle Cerebral Artery Occlusion","authors":"E. Yu. Zavarina, E. K. Krasova, I. A. Titovich, A. N. Kimaev","doi":"10.33380/2305-2066-2023-12-4-1584","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1584","url":null,"abstract":"Introduction. Cerebrovascular diseases (CVD) are one of the most pressing medical and social problems due to the high rate of mortality and disability. Stroke is the leading cause of CVD. About 15 million strokes are registered annually in the world according to the World Federation of Neurological Societies. It should be noted that CVD of ischemic origin has a tendency to rejuvenation and growth. Traditionally, in clinical practice, antihypoxic, antioxidant agents, as well as drugs with neuroprotective and neurorehabilitation effects are used to treat CVD. In connection with the increase in the incidence of CVD, there is an urgent need to search for promising neuroprotectors. Aim. To study the neuroprotective activity of 5-ethoxy-2-ethylthiobenzimidazole (etomerzol) and 2-ethylthiobenzimidazole (bemityl) in a model of middle cerebral artery occlusion. Materials and methods. Occlusion of the middle cerebral artery (ОMCA) was used as a model. The object of the study was inbred male rats of the Dark Agouti line, randomized into five groups: a group of intact animals and four groups with OSMA: a control group, a group with the introduction of 5-ethoxy-2-ethylthiobenzimidazole (etomerzole, 25 mg/kg), a group with the introduction 2-ethylthiobenzimidazole (bemityl, 25 mg/kg) and a group with the reference drug dimethyl fumarate (DMF, 100 mg/kg). On the 1st, 3rd, and 7th days after the operation, the \"Limb Stimulation\" (SC) test was performed. On the 7th day, the tests \"Open field\" (OP) and \"Elevated plus maze\" (EPM) were performed. Euthanasia was performed on the 7th day in an induction chamber (Bioscape GmbH, CO 2 box for euthanasia, Germany). Results and discussion. The study showed a pronounced pharmacological effect of etomerzole in a model of acute ischemic stroke. The introduction of bemitil, etomerzol and DMF significantly reduced the neurological deficit 24 hours after OSMA and improved the psycho-functional state on the 7th day. Thus, in the etomerzol group on the first day after surgery, the neurological deficit was reduced by 1.9 times ( p < 0.05), and by 3 and 2.0 times ( p < 0.05) compared with the control group. While bemityl and DMF reduced the index by 1.3 ( p < 0.05) and 1.4 times ( p < 0.05) on the 3rd day and by 1.5 times ( p < 0.05) on the 7th day. In the OP test in the etomerzol group, an increase in HDA by 2.7 times ( p < 0.05) was observed compared with the control. The rate of peering into minks in the etomersol and bemitil groups was higher than in the control group by 2.6 ( p < 0.05) and 3.4 times ( p < 0.05), respectively. Search and research activity was increased in the same groups by 2.0 ( p < 0.05) and 2.2 times ( p < 0.05) compared to control animals. In the PCL test, the etomerzol and DMF groups showed an increase in the number of uprights in the sleeves compared to the control group by 2.7 ( p < 0.05) and 3.8 times ( p < 0.05), respectively. In the etomerzol and bemityl groups, there was an increase in the number of o","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136012618","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 : 2023-10-12DOI: 10.33380/2305-2066-2023-12-4-1585
G. N. Turmanidze, V. V. Sorokin, K. S. Stepanov, M. A. Ignatenko
Introduction. Improving the technologies for isolating and purifying biologically active substances from plant materials is an important task for the pharmaceutical, food and cosmetic industries. Technology development often requires changes to the design of existing equipment. During the modernization of equipment for the implementation of new technologies, it is possible to improve its configuration, which makes it possible to significantly increase the yield of active substances at minimal cost. To increase the efficiency of the process of isolating hesperidin from plant materials, we proposed to use a number of technological solutions. In particular, it is proposed to use mixing devices with the configuration of impellers obtained by computational fluid dynamics, when using a Soxhlet extractor to use a heated extraction chamber, by adding an external coil jacket, which makes it possible to regulate the temperature inside the extraction chamber to accelerate the processes of diffusion and mass transfer, and to select the solvent and extractant on the basis of thermodynamic models by calculation. Aim. Improving the technology for isolating and purifying hesperidin from plant materials using modernized equipment. Materials and methods. Flow distribution in extraction apparatuses was modeled using computational fluid dynamics methods. To evaluate the results obtained on the basis of modeling, a number of experiments were carried out, the object of which was the peel of an orange (dried flavedo and albedo, grinding degree 0.1–0.2 mm, moisture content 3.5 %). The quantitative content of the flavonoid complex in terms of hesperidin was determined by direct spectrophotometry at a wavelength of 290 nm, the quantitative content of hesperidin was determined gravimetrically. Statistical data processing was performed using Minitab v21 software (Minitab Inc., USA), differences were considered statistically significant at p < 0.05. Results and discussion. Based on the methods of computational fluid dynamics, to intensify the processes of mixing and dissolution at the stages of preliminary degreasing of raw materials and extraction, a six-bladed impeller was designed, which makes it possible to accelerate these processes by creating axial and radial flows of fluid movement in a capacitive apparatus and maintaining raw materials in suspended state in the volume of liquid at low mixing speeds and energy consumption. Equipping the extraction chamber with a coiled jacket made it possible to significantly increase the solubility of the active substance and extract more of the target component in one extraction cycle. A technology for the isolation and purification of hesperidin was developed, and the parameters of the processes were determined and optimized. Conclusion. As a result of the study, it was shown that it is possible to intensify the processes of extraction and dissolution of active substances by selecting mixing devices using the method of computation
{"title":"Improvement of Technologies for Isolation and Purification of Biologically Active Substances from Plant Raw Materials","authors":"G. N. Turmanidze, V. V. Sorokin, K. S. Stepanov, M. A. Ignatenko","doi":"10.33380/2305-2066-2023-12-4-1585","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1585","url":null,"abstract":"Introduction. Improving the technologies for isolating and purifying biologically active substances from plant materials is an important task for the pharmaceutical, food and cosmetic industries. Technology development often requires changes to the design of existing equipment. During the modernization of equipment for the implementation of new technologies, it is possible to improve its configuration, which makes it possible to significantly increase the yield of active substances at minimal cost. To increase the efficiency of the process of isolating hesperidin from plant materials, we proposed to use a number of technological solutions. In particular, it is proposed to use mixing devices with the configuration of impellers obtained by computational fluid dynamics, when using a Soxhlet extractor to use a heated extraction chamber, by adding an external coil jacket, which makes it possible to regulate the temperature inside the extraction chamber to accelerate the processes of diffusion and mass transfer, and to select the solvent and extractant on the basis of thermodynamic models by calculation. Aim. Improving the technology for isolating and purifying hesperidin from plant materials using modernized equipment. Materials and methods. Flow distribution in extraction apparatuses was modeled using computational fluid dynamics methods. To evaluate the results obtained on the basis of modeling, a number of experiments were carried out, the object of which was the peel of an orange (dried flavedo and albedo, grinding degree 0.1–0.2 mm, moisture content 3.5 %). The quantitative content of the flavonoid complex in terms of hesperidin was determined by direct spectrophotometry at a wavelength of 290 nm, the quantitative content of hesperidin was determined gravimetrically. Statistical data processing was performed using Minitab v21 software (Minitab Inc., USA), differences were considered statistically significant at p < 0.05. Results and discussion. Based on the methods of computational fluid dynamics, to intensify the processes of mixing and dissolution at the stages of preliminary degreasing of raw materials and extraction, a six-bladed impeller was designed, which makes it possible to accelerate these processes by creating axial and radial flows of fluid movement in a capacitive apparatus and maintaining raw materials in suspended state in the volume of liquid at low mixing speeds and energy consumption. Equipping the extraction chamber with a coiled jacket made it possible to significantly increase the solubility of the active substance and extract more of the target component in one extraction cycle. A technology for the isolation and purification of hesperidin was developed, and the parameters of the processes were determined and optimized. Conclusion. As a result of the study, it was shown that it is possible to intensify the processes of extraction and dissolution of active substances by selecting mixing devices using the method of computation","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136012878","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 : 2023-10-06DOI: 10.33380/2305-2066-2023-12-4-1586
K. S. Stepanov, G. N. Turmanidze, V. V. Sorokin, A. D. Sakharov
Introduction. The choice of solvents for the processes of extraction of biologically active substances from natural raw materials, the processes of purification of natural and synthesized substances by extraction, crystallization and dissolution methods is an important problem of the modern pharmaceutical industry, because a large number of experiments must be performed to determine the optimal solvent or mixture of solvents. To reduce the cost of developing and optimizing the extraction and purification of substances stages, it is proposed to use thermodynamic models at the stage of preliminary solubility assessment. The article investigates predicting the solubility of pharmaceutical substances issue on the example of the technology for isolating hesperidin and glycyrrhizic acid from plant materials. Aim. Theoretical determination of the dissolving power of various solvents with respect to hesperidin and glycyrrhizic acid. Materials and methods. The PMUNIFAC and NRTL-SAC thermodynamic models were used to predict solubility. The solubility calculation for the NRTL-SAC model was performed using Aspen Properties V14 software, and for the PMUNIFAC model using PTC Mathcad Prime V6. To evaluate the results obtained using thermodynamic models, a number of experiments were carried out, the object of which was the peel of an orange (dried flavedo and albedo, the degree of grinding is 0.2–0.5 mm, the moisture content is 8 %). The quantitative content of hesperidin was determined by direct spectrophotometry at a wavelength of 290 nm. Statistical data processing was performed using Minitab v20 software (Minitab Inc., USA), differences were considered statistically significant at p < 0.05. Results and discussion. On the basis of thermodynamic models, the prediction of the solubility of hesperidin and glycyrrhizic acid was made. It has been shown that the solubility can be assessed both in the presence of solubility data according to the NRTL-SAC model, and in their complete absence according to PMUNIFAC. The correspondence of the theoretically calculated data to the experimental data confirms the correctness of the calculations of thermodynamic models. The results of the calculations are evaluated and solvents are recommended that can be used in the technology of isolating hesperidin and glycyrrhizic for the stages of degreasing, extraction and crystallization with the antisolvent. Conclusion. Using the NRTL-SAC and PMUNIFAC thermodynamic models, the dissolving power of various solvents with respect to hesperidin and glycyrrhizic acid was determined. From the calculation results, a list of solvents was built, ranked by the solubility of the studied substances in them. The resulting list can be used in the development of an industrial technology for the isolation and purification of hesperidin and glycyrrhizic acid. It is shown that the NRTL-SAC and PMUNIFAC models have good prospects for quantitative prediction of the solubility of active substances.
{"title":"Application of Thermodynamic Models to Predict the Solubility of Biologically Active Substances","authors":"K. S. Stepanov, G. N. Turmanidze, V. V. Sorokin, A. D. Sakharov","doi":"10.33380/2305-2066-2023-12-4-1586","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1586","url":null,"abstract":"Introduction. The choice of solvents for the processes of extraction of biologically active substances from natural raw materials, the processes of purification of natural and synthesized substances by extraction, crystallization and dissolution methods is an important problem of the modern pharmaceutical industry, because a large number of experiments must be performed to determine the optimal solvent or mixture of solvents. To reduce the cost of developing and optimizing the extraction and purification of substances stages, it is proposed to use thermodynamic models at the stage of preliminary solubility assessment. The article investigates predicting the solubility of pharmaceutical substances issue on the example of the technology for isolating hesperidin and glycyrrhizic acid from plant materials. Aim. Theoretical determination of the dissolving power of various solvents with respect to hesperidin and glycyrrhizic acid. Materials and methods. The PMUNIFAC and NRTL-SAC thermodynamic models were used to predict solubility. The solubility calculation for the NRTL-SAC model was performed using Aspen Properties V14 software, and for the PMUNIFAC model using PTC Mathcad Prime V6. To evaluate the results obtained using thermodynamic models, a number of experiments were carried out, the object of which was the peel of an orange (dried flavedo and albedo, the degree of grinding is 0.2–0.5 mm, the moisture content is 8 %). The quantitative content of hesperidin was determined by direct spectrophotometry at a wavelength of 290 nm. Statistical data processing was performed using Minitab v20 software (Minitab Inc., USA), differences were considered statistically significant at p < 0.05. Results and discussion. On the basis of thermodynamic models, the prediction of the solubility of hesperidin and glycyrrhizic acid was made. It has been shown that the solubility can be assessed both in the presence of solubility data according to the NRTL-SAC model, and in their complete absence according to PMUNIFAC. The correspondence of the theoretically calculated data to the experimental data confirms the correctness of the calculations of thermodynamic models. The results of the calculations are evaluated and solvents are recommended that can be used in the technology of isolating hesperidin and glycyrrhizic for the stages of degreasing, extraction and crystallization with the antisolvent. Conclusion. Using the NRTL-SAC and PMUNIFAC thermodynamic models, the dissolving power of various solvents with respect to hesperidin and glycyrrhizic acid was determined. From the calculation results, a list of solvents was built, ranked by the solubility of the studied substances in them. The resulting list can be used in the development of an industrial technology for the isolation and purification of hesperidin and glycyrrhizic acid. It is shown that the NRTL-SAC and PMUNIFAC models have good prospects for quantitative prediction of the solubility of active substances.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"121 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135351963","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 : 2023-09-27DOI: 10.33380/2305-2066-2023-12-4-1581
D. A. Nekrasova, M. N. Povydysh, N. S. Pivovarova, K. O. Sidorov
Introduction. Cell cultures spreads widely in different areas of biology, biotechnology and agriculture. Aralia cordata is a perennial herbaceous plant, which has been listed in Red book of the Russian Federation. Pharmaceuticals which are based on raw materials of Aralia ssp. have valuable types of pharmacological activity and are widely used in oriental medicine. A serious obstacle for resumption of the natural populations is the presence of the period of morphophysiological dormancy in the seeds of the plants, which requires a long-time stratification process. Limitation of the natural geographic range and the combination of biological activities useful for humans make Aralia cordata Thunb. prospective object for in vitro introduction. Aim. The aim of the study is obtaining of the viable cell culture of Aralia cordata Thunb., investigation of the somatic embryogenesis conditions. Materials and methods. Pieces of the leaves of Aralia cordata intact plant from Komarov Botanical Institute of the Russian Academy of Sciences were used as a primary explants. Pieces of leaves were sterilized in a 2 % benzalkonium chloride solution for 5 minutes, induction of primary callogenesis was carried out on Murasige – Skoog medium. Nutrient media with different constituents were discovered for choosing one for long-time cultivation of calli. Induction of somatic embryogenesis was carried out on the nutrient media with high auxins content. Ethanol extracts from the intact plant and calli cultures were assayed with HPTLC PRO SYSTEM (CAMAG AG, Switzerland). Results and discussion. After two weeks of cultivation, the formation of primary callus was observed on the surface of the explants. The Linsmaier – Skoog medium with a reduced amount of sucrose (20 g/l) was recognized as the most suitable medium for long-term maintenance of cultures. Embryoid structures of Aralia cordata have been obtained, now we are continuing to collect analytics data about this process. Qualitative analysis of the extracts showed that callus cultures accumulate triterpene glycosides, their composition is close to that of the intact plant. Conclusion. A viable strain of callus culture of Aralia cordata Thunb. was obtained, a nutrient medium for long-term cultivation of calli was established. Somatic embryoids have been obtained, and their further development is currently being monitored. A preliminary phytochemical study showed that the composition of the chemical components of calli is close to that of an intact plant.
{"title":"Callus Culture of <i>Aralia cordata</i> Thunb.: Obtaining, Selection of Cultivating Conditions, Somatic Embryogenesis Induction","authors":"D. A. Nekrasova, M. N. Povydysh, N. S. Pivovarova, K. O. Sidorov","doi":"10.33380/2305-2066-2023-12-4-1581","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1581","url":null,"abstract":"Introduction. Cell cultures spreads widely in different areas of biology, biotechnology and agriculture. Aralia cordata is a perennial herbaceous plant, which has been listed in Red book of the Russian Federation. Pharmaceuticals which are based on raw materials of Aralia ssp. have valuable types of pharmacological activity and are widely used in oriental medicine. A serious obstacle for resumption of the natural populations is the presence of the period of morphophysiological dormancy in the seeds of the plants, which requires a long-time stratification process. Limitation of the natural geographic range and the combination of biological activities useful for humans make Aralia cordata Thunb. prospective object for in vitro introduction. Aim. The aim of the study is obtaining of the viable cell culture of Aralia cordata Thunb., investigation of the somatic embryogenesis conditions. Materials and methods. Pieces of the leaves of Aralia cordata intact plant from Komarov Botanical Institute of the Russian Academy of Sciences were used as a primary explants. Pieces of leaves were sterilized in a 2 % benzalkonium chloride solution for 5 minutes, induction of primary callogenesis was carried out on Murasige – Skoog medium. Nutrient media with different constituents were discovered for choosing one for long-time cultivation of calli. Induction of somatic embryogenesis was carried out on the nutrient media with high auxins content. Ethanol extracts from the intact plant and calli cultures were assayed with HPTLC PRO SYSTEM (CAMAG AG, Switzerland). Results and discussion. After two weeks of cultivation, the formation of primary callus was observed on the surface of the explants. The Linsmaier – Skoog medium with a reduced amount of sucrose (20 g/l) was recognized as the most suitable medium for long-term maintenance of cultures. Embryoid structures of Aralia cordata have been obtained, now we are continuing to collect analytics data about this process. Qualitative analysis of the extracts showed that callus cultures accumulate triterpene glycosides, their composition is close to that of the intact plant. Conclusion. A viable strain of callus culture of Aralia cordata Thunb. was obtained, a nutrient medium for long-term cultivation of calli was established. Somatic embryoids have been obtained, and their further development is currently being monitored. A preliminary phytochemical study showed that the composition of the chemical components of calli is close to that of an intact plant.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135587265","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 : 2023-09-26DOI: 10.33380/2305-2066-2023-12-4-1525
E. P. Pavlenko, A. A. Larenkov, Iu. A. Mitrofanov
Introduction. The use of radiopharmaceuticals for targeted radionuclide therapy (TRT), the efficacy of which was established during clinical trials, is safe and effective for various pathological conditions, including cancer. The main feature of therapeutic radiopharmaceuticals (RPs) is the use of β – - and α-emitting radionuclides (RNs) in the finished dosage form (FD). Among the radionuclides used for radionuclide therapy, lutetium-177 is currently one of the most popular in clinical practice because of its chemical and nuclear characteristics. The list of RPs based on lutetium-177 is constantly expanding, and Lutathera® ([ 177 Lu]Lu-DOTA-TATE) and Pluvicto™ ([ 177 Lu]Lu-PSMA-617) have been approved for clinical use in several countries. Text. Because of the high activity of RNs in a single dose of therapeutic RPs (up to 8 GBq in a monodose for 177 Lu), ionizing radiation of the used RNs leads to a decrease in RPs quality owing to radiolytic degradation of the vector molecule. This leads to a decreased specific accumulation of radioactivity in the foci of pathology, reduced therapeutic effect, and potentially increases the risk of radiotoxicity to non-target organs and tissues. The degree and intensity of radiolytic degradation of the vector molecule and, consequently, the shelf life of RPs depend on many factors, among which the activity concentration of the radionuclide in the preparation, its half-life, and the energy of the emitted particles are the most important. To suppress the effects of radiolysis, various excipients with antioxidant (radioprotective) properties were introduced into the compositions of the finished dosage forms. Among the substances studied, the most popular were gentisic acid, ascorbic acid, and ethanol. In this work, the advantages and disadvantages of various antioxidants and their combinations used in therapeutic RPs were considered in lutetium-177 preparations. Conclusion. Selection of the optimal composition of the dosage form is an urgent task, as it will ensure high-quality RPs both at the time of preparation and during the shelf life and delivery to the end user, which will greatly facilitate the use and centralized supply of therapeutic RPs. The necessity of creating a unified approach for the selection of antioxidants at the pharmaceutical development stage of radiopharmaceuticals is shown. For this purpose, an approach combining studies of radical reaction kinetics with studies of radiation-chemical yields of radiolysis products under identical or maximally similar conditions with subsequent verification of the stability of RPs dosage form seems to be very promising and has proven to be effective. In contrast, the empirical approach, which implies the selection of radioprotectors based on a direct study of their influence on the preservation of the level of radiochemical purity, is suboptimal because of the high market value of both radionuclides and non-radioactive precursors.
{"title":"Selection and Use of Antioxidants-radioprotectors in the Composition of Therapeutic Radiopharmaceuticals (Review)","authors":"E. P. Pavlenko, A. A. Larenkov, Iu. A. Mitrofanov","doi":"10.33380/2305-2066-2023-12-4-1525","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-4-1525","url":null,"abstract":"Introduction. The use of radiopharmaceuticals for targeted radionuclide therapy (TRT), the efficacy of which was established during clinical trials, is safe and effective for various pathological conditions, including cancer. The main feature of therapeutic radiopharmaceuticals (RPs) is the use of β – - and α-emitting radionuclides (RNs) in the finished dosage form (FD). Among the radionuclides used for radionuclide therapy, lutetium-177 is currently one of the most popular in clinical practice because of its chemical and nuclear characteristics. The list of RPs based on lutetium-177 is constantly expanding, and Lutathera® ([ 177 Lu]Lu-DOTA-TATE) and Pluvicto™ ([ 177 Lu]Lu-PSMA-617) have been approved for clinical use in several countries. Text. Because of the high activity of RNs in a single dose of therapeutic RPs (up to 8 GBq in a monodose for 177 Lu), ionizing radiation of the used RNs leads to a decrease in RPs quality owing to radiolytic degradation of the vector molecule. This leads to a decreased specific accumulation of radioactivity in the foci of pathology, reduced therapeutic effect, and potentially increases the risk of radiotoxicity to non-target organs and tissues. The degree and intensity of radiolytic degradation of the vector molecule and, consequently, the shelf life of RPs depend on many factors, among which the activity concentration of the radionuclide in the preparation, its half-life, and the energy of the emitted particles are the most important. To suppress the effects of radiolysis, various excipients with antioxidant (radioprotective) properties were introduced into the compositions of the finished dosage forms. Among the substances studied, the most popular were gentisic acid, ascorbic acid, and ethanol. In this work, the advantages and disadvantages of various antioxidants and their combinations used in therapeutic RPs were considered in lutetium-177 preparations. Conclusion. Selection of the optimal composition of the dosage form is an urgent task, as it will ensure high-quality RPs both at the time of preparation and during the shelf life and delivery to the end user, which will greatly facilitate the use and centralized supply of therapeutic RPs. The necessity of creating a unified approach for the selection of antioxidants at the pharmaceutical development stage of radiopharmaceuticals is shown. For this purpose, an approach combining studies of radical reaction kinetics with studies of radiation-chemical yields of radiolysis products under identical or maximally similar conditions with subsequent verification of the stability of RPs dosage form seems to be very promising and has proven to be effective. In contrast, the empirical approach, which implies the selection of radioprotectors based on a direct study of their influence on the preservation of the level of radiochemical purity, is suboptimal because of the high market value of both radionuclides and non-radioactive precursors.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134960841","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 : 2023-08-31DOI: 10.33380/2305-2066-2023-12-3-143-150
O. G. Shapoval, A. S. Sheremetyeva, N. A. Durnova, N. Q. Mukhamadiev, G. T. Rabbimova, M. K. Nazirbekov, M. A. Kupryashina
Introduction. Plant essential oils are supposed to be applied for local treatment of infectious focuses. Aim. The aim of this study was evaluation of antimicrobial activity of essential oils of Thymus serpyllum L. and Thymus marschallianus Willd., widely distributed in the Saratov region. Materials and methods. Antimicrobial activity of the essential oils was determined by a serial dilution test at the microbial number of 5 × 10 5 CFU/ml against 6 strains of Staphylococcus aureus , including S. aureus FDA 209P and five clinical, 2 strains of Escherichia coli – E. coli ATCC 25922 and one clinical, two strains of Pseudomonas aeruginosa – P. aeruginosa ATCC 27835 and one clinical. Results and discussion. The bactericidal minimal inhibitory concentrations (MICs) of essential oil of T. serpyllum were determined for all strains of staphylococci (for 5 – 1097,5, for 1 – 2195 µg/ml). The bacteriostatic MICs were determined for 3 strains (for 2 – 548,75, for 1 – 1097,5 µg/ml). MICs of the T. marschallianus essential oil were bactericidal for all strains of S. aureus (120 for 5 and 480 µg/ml for 1 strain). For all test strains of gram-negative bacteria MICs of the essential oils of both species were bactericidal and amounted to 1097 and 960 µg/ml. Considering the chemical composition of the oils by thymol and its isomers, MIC 50 of T. marschallianus and T. serpyllum for the test staphylococcal strains amounted 108,89 and 496,59, for the test strains of gram-negative bacteria 683,91 and 783,43 µg/ml respectively. Conclusion. According to the values of MIC 50 antistaphylococcal activity of the essential oils of T. marschallianus was significantly higher than this activity of the essential oils of T. serpyllum .
{"title":"Antibacterial Activity of Essential Oils of <i>Thymus serpyllum</i> L. and <i>Thymus marschallianus</i> Willd.","authors":"O. G. Shapoval, A. S. Sheremetyeva, N. A. Durnova, N. Q. Mukhamadiev, G. T. Rabbimova, M. K. Nazirbekov, M. A. Kupryashina","doi":"10.33380/2305-2066-2023-12-3-143-150","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-143-150","url":null,"abstract":"Introduction. Plant essential oils are supposed to be applied for local treatment of infectious focuses. Aim. The aim of this study was evaluation of antimicrobial activity of essential oils of Thymus serpyllum L. and Thymus marschallianus Willd., widely distributed in the Saratov region. Materials and methods. Antimicrobial activity of the essential oils was determined by a serial dilution test at the microbial number of 5 × 10 5 CFU/ml against 6 strains of Staphylococcus aureus , including S. aureus FDA 209P and five clinical, 2 strains of Escherichia coli – E. coli ATCC 25922 and one clinical, two strains of Pseudomonas aeruginosa – P. aeruginosa ATCC 27835 and one clinical. Results and discussion. The bactericidal minimal inhibitory concentrations (MICs) of essential oil of T. serpyllum were determined for all strains of staphylococci (for 5 – 1097,5, for 1 – 2195 µg/ml). The bacteriostatic MICs were determined for 3 strains (for 2 – 548,75, for 1 – 1097,5 µg/ml). MICs of the T. marschallianus essential oil were bactericidal for all strains of S. aureus (120 for 5 and 480 µg/ml for 1 strain). For all test strains of gram-negative bacteria MICs of the essential oils of both species were bactericidal and amounted to 1097 and 960 µg/ml. Considering the chemical composition of the oils by thymol and its isomers, MIC 50 of T. marschallianus and T. serpyllum for the test staphylococcal strains amounted 108,89 and 496,59, for the test strains of gram-negative bacteria 683,91 and 783,43 µg/ml respectively. Conclusion. According to the values of MIC 50 antistaphylococcal activity of the essential oils of T. marschallianus was significantly higher than this activity of the essential oils of T. serpyllum .","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135946762","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 : 2023-08-30DOI: 10.33380/2305-2066-2023-12-3-134-142
A. M. Poluyanov, A. Yu. Sokolova, A.-D. Koynova, S. D. Kulikova, E. A. Malashenko, N. V. Bobkova
Introduction. The study of the dynamics of accumulation of biologically active substances (hereinafter – BAS) in relation to the phonological phases of plant development is of great scientific and practical interest. The quantitative content of aglycones and glycosides of flavonoids depends on the life cycle of the plant and its vegetation phase. Aim. To identify and quantify flavonoids in the underground organs of Rumex confertus Willd., Rumex aquaticus L., Rumex crispus L. and Rumex obtusifolius L. harvested during different phases of vegetation. Materials and methods. Extracts from the underground organs of the studied plants, obtained according to the method from the pharmacopoeial article on R. confertus , were analyzed. Chromatographic separation and detection were performed on a Nexera-i LC-2040 high-performance liquid chromatograph (Shimadzu Corporation, Japan). The chromatograph was equipped with a column thermostat, chromatography column Grace HPLC-COLUMN 250 × 4.6mm platinum C8-EPS 5 mm (Grace, США) and Guard column Phenomenex SecurityGuard TM Cartridges Widepore C18 4 × 3,0 mm, a degasser, an autosampler (injection volume: 10 µl), and an ultraviolet detector. Detection was carried out at a wavelength λ = 365 ± 2 nm. Mobile phase contains 0.1 % phosphoric acid in water (v/v) (eluent A); acetonitrile (eluent B) with flow rate: 0.9 ml/min. Results and discussion. All studied objects were analyzed. The authenticity of the substances contained were confirmed using the external standard, and their quantitative content was determined. The discovered and quantified substances were: 3-O-rutinoside of quercetin (rutin), 3-O-rutinoside of isorhamnetin (narcissin), 3-O-glucoside of kaempferol (astragalin), luteolin, kaempferol and isorhamnetin. 7-O-glucoside of luteolin (cynaroside) and 7-O-beta-D-glucoside apigenin (cosmosiin) were not found. The aglycone luteolin had the biggest share in the total quantitative content of flavonoids. It is noted that this aglycone is contained in larger quantities in relation to other flavonoids in all studied objects, regardless of the phase of vegetation. Conclusion. In the process of the research, a method for the quantitative determination of flavonoids in alcohol-water extracts was developed. Aglycones and glycosides of flavonoids were identified and quantified in the underground organs of R. confertus Willd., R. aquaticus L., R. crispus L. and R. obtusifolius L. of three different vegetations.
介绍。研究生物活性物质(以下简称BAS)的积累动态与植物发育的音韵学阶段的关系具有重大的科学和实用意义。黄酮类化合物中苷元和苷类的定量含量取决于植物的生命周期和生长阶段。的目标。目的:鉴定并定量黄酮类化合物。不同植被时期采收的水叶柳、山梨柳和黑叶柳。材料和方法。用该方法从药典文章中提取了所研究植物的地下器官提取物，并进行了分析。采用Nexera-i LC-2040高效液相色谱仪(Shimadzu Corporation, Japan)进行色谱分离和检测。色谱仪配备柱恒温器、色谱柱Grace HPLC-COLUMN 250 × 4.6mm铂C8-EPS 5mm (Grace， США)和保护柱Phenomenex SecurityGuard TM cartridge Widepore C18 4 × 3,0 mm、脱气器、自动进样器(进样量:10µl)和紫外检测器。检测波长为λ = 365±2 nm。流动相含0.1%磷酸水溶液(v/v)(洗脱液A);乙腈(洗脱液B)，流速:0.9 ml/min。结果和讨论。对所有研究对象进行分析。采用外标法确认所含物质的真伪，并测定其定量含量。发现并定量的物质为:槲皮素(芦丁)中的3- o -芦丁苷、异鼠李素(水仙素)中的3- o -芦丁苷、山奈酚(黄芪甲苷)中的3- o -葡萄糖苷、木犀草素、山奈酚和异鼠李素。未发现木犀草素7- o -葡糖苷(cynaroside)和7- o - β - d -葡糖苷芹菜素(cosmosiin)。其中木犀草素苷元在总黄酮定量含量中所占比例最大。值得注意的是，在所有研究对象中，与其他类黄酮相比，这种苷元的含量更高，而与植被的阶段无关。结论。在研究过程中，建立了醇水提取物中黄酮类化合物含量的定量测定方法。测定了黄芪地下器官中黄酮类化合物的苷元和苷类成分。3种不同植被下的水杨、山竹和粗叶山竹。
{"title":"Identification and Quantitative Determination of Flavonoids by HPLC-UV Method in the Raw Materials of Some Representatives of the Genus <i>Rumex</i> of Three Vegetation Time","authors":"A. M. Poluyanov, A. Yu. Sokolova, A.-D. Koynova, S. D. Kulikova, E. A. Malashenko, N. V. Bobkova","doi":"10.33380/2305-2066-2023-12-3-134-142","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-134-142","url":null,"abstract":"Introduction. The study of the dynamics of accumulation of biologically active substances (hereinafter – BAS) in relation to the phonological phases of plant development is of great scientific and practical interest. The quantitative content of aglycones and glycosides of flavonoids depends on the life cycle of the plant and its vegetation phase. Aim. To identify and quantify flavonoids in the underground organs of Rumex confertus Willd., Rumex aquaticus L., Rumex crispus L. and Rumex obtusifolius L. harvested during different phases of vegetation. Materials and methods. Extracts from the underground organs of the studied plants, obtained according to the method from the pharmacopoeial article on R. confertus , were analyzed. Chromatographic separation and detection were performed on a Nexera-i LC-2040 high-performance liquid chromatograph (Shimadzu Corporation, Japan). The chromatograph was equipped with a column thermostat, chromatography column Grace HPLC-COLUMN 250 × 4.6mm platinum C8-EPS 5 mm (Grace, США) and Guard column Phenomenex SecurityGuard TM Cartridges Widepore C18 4 × 3,0 mm, a degasser, an autosampler (injection volume: 10 µl), and an ultraviolet detector. Detection was carried out at a wavelength λ = 365 ± 2 nm. Mobile phase contains 0.1 % phosphoric acid in water (v/v) (eluent A); acetonitrile (eluent B) with flow rate: 0.9 ml/min. Results and discussion. All studied objects were analyzed. The authenticity of the substances contained were confirmed using the external standard, and their quantitative content was determined. The discovered and quantified substances were: 3-O-rutinoside of quercetin (rutin), 3-O-rutinoside of isorhamnetin (narcissin), 3-O-glucoside of kaempferol (astragalin), luteolin, kaempferol and isorhamnetin. 7-O-glucoside of luteolin (cynaroside) and 7-O-beta-D-glucoside apigenin (cosmosiin) were not found. The aglycone luteolin had the biggest share in the total quantitative content of flavonoids. It is noted that this aglycone is contained in larger quantities in relation to other flavonoids in all studied objects, regardless of the phase of vegetation. Conclusion. In the process of the research, a method for the quantitative determination of flavonoids in alcohol-water extracts was developed. Aglycones and glycosides of flavonoids were identified and quantified in the underground organs of R. confertus Willd., R. aquaticus L., R. crispus L. and R. obtusifolius L. of three different vegetations.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136144274","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 : 2023-05-29DOI: 10.33380/2305-2066-2023-12-2-190-197
M. A. Kolganova, O. S. Sagimbaeva, Ju. S. Borisova, E. E. Beketov, I. E. Shokhin
Introduction. Trastuzumab is the first known anti-HER2 agent, which revolutionized the treatment of one of the most common cancer types – breast cancer. Despite trastuzumab being approved long time ago, further improvement of related analytical methods remains relevant primarily due to the emergence of new biosimilars. For instance, immunogenicity – adverse reaction which is usually associated with biological drugs, can still be relevant for trastuzumab. Anti-drug antibodies, including neutralizing antibodies, caused by trastuzumab therapy, can affect drug effectiveness and safety profile. Aim. The aim of this study was to develop and validate the analytical method for neutralizing anti-trastuzumab antibodies determination in human blood serum. Materials and methods. The neutralizing anti-trastuzumab antibody determination was carried out by the competitive ELISA method, using spectrophotometric detection in the visible range of the spectrum. Results and discussion. The developed method was validated for cut-point, selectivity, sensitivity, specificity, precision and stability (short-term and long-term). To decrease the background noise from non-specific binding of sera components, the minimum required dilution value was determined at 0.5 % serum. The calculated value for cut-point was 14.62 %. The sensitivity of the developed method was estimated at 1985.2 ng/mL of neutralizing anti-trastuzumab antibodies. Conclusion. The obtained results allowed us to apply the developed ELISA method for the neutralizing anti-trastuzumab antibodies determination in human blood serum during trastuzumab immunogenicity assessment in bioequivalence clinical trials.
{"title":"Development and Validation of the ELISA Method for Neutralizing Anti-trastuzumab Antibodies Detection in Human Blood Serum","authors":"M. A. Kolganova, O. S. Sagimbaeva, Ju. S. Borisova, E. E. Beketov, I. E. Shokhin","doi":"10.33380/2305-2066-2023-12-2-190-197","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-2-190-197","url":null,"abstract":"Introduction. Trastuzumab is the first known anti-HER2 agent, which revolutionized the treatment of one of the most common cancer types – breast cancer. Despite trastuzumab being approved long time ago, further improvement of related analytical methods remains relevant primarily due to the emergence of new biosimilars. For instance, immunogenicity – adverse reaction which is usually associated with biological drugs, can still be relevant for trastuzumab. Anti-drug antibodies, including neutralizing antibodies, caused by trastuzumab therapy, can affect drug effectiveness and safety profile. Aim. The aim of this study was to develop and validate the analytical method for neutralizing anti-trastuzumab antibodies determination in human blood serum. Materials and methods. The neutralizing anti-trastuzumab antibody determination was carried out by the competitive ELISA method, using spectrophotometric detection in the visible range of the spectrum. Results and discussion. The developed method was validated for cut-point, selectivity, sensitivity, specificity, precision and stability (short-term and long-term). To decrease the background noise from non-specific binding of sera components, the minimum required dilution value was determined at 0.5 % serum. The calculated value for cut-point was 14.62 %. The sensitivity of the developed method was estimated at 1985.2 ng/mL of neutralizing anti-trastuzumab antibodies. Conclusion. The obtained results allowed us to apply the developed ELISA method for the neutralizing anti-trastuzumab antibodies determination in human blood serum during trastuzumab immunogenicity assessment in bioequivalence clinical trials.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135792815","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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