Pub Date : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-54-63
E. Bakhrushina, N. Demina, M. Shumkova, P. S. Rodyuk, D. S. Shulikina, I. Krasnyuk
Introduction. Intranasal delivery of in situ gel-forming systems is a complex but promising direction. Due to the high cost of developing a new chemical object or genetically engineered modification of biological molecules, pharmaceutical companies are focusing on developing technologies for new delivery systems for existing active pharmaceutical ingredients to improve their effectiveness and bioavailability. In situ systems for intranasal delivery, due to increased viscosity and mucoadhesion to the nasal mucosa, allow overcoming mucociliary clearance and ensuring complete absorption and prolonged release of drugs.Text. The article discusses the main advantages of intranasal in situ delivery systems shown in preclinical studies, as well as approaches to the technology of obtaining and standardization of these systems. The results of scientific research in this field over the past 15 years are summarized, the most promising polymers for creating thermoreversible and pH-sensitive compositions are identified, and modern methods for evaluating the sol-gel transition in situ are analyzed.Conclusion. The use of in situ systems for intranasal administration allows providing a high targeting of the delivery of synthetic and biological molecules to the brain. Currently, numerous pharmacokinetic and pharmacodynamic preclinical studies confirm the effectiveness of such systems, as well as their safety. Thermoreversible commercially available and directionally synthesized polymers (poloxamer 407, PLGA, NIPAAm, etc.), as well as chitosan, remain the most popular for the design of in situ delivery systems. In vitro and ex vivo methods with mucosa and artificial nasal fluid are widely used to assess the parameters of in situ gelation, but to increase the reproducibility of the methods and improve the correlation in vitro/in vivo, it is recommended to conduct modeling of the nasal cavity. Developing the technology and methods of screening of intranasal reversible systems will help to get closer to clinical trials and the entry of these delivery systems into the global pharmaceutical market.
{"title":"In situ Intranasal Delivery Systems: Application Prospects and Main Pharmaceutical Aspects of Development (Review)","authors":"E. Bakhrushina, N. Demina, M. Shumkova, P. S. Rodyuk, D. S. Shulikina, I. Krasnyuk","doi":"10.33380/2305-2066-2021-10-4-54-63","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-54-63","url":null,"abstract":"Introduction. Intranasal delivery of in situ gel-forming systems is a complex but promising direction. Due to the high cost of developing a new chemical object or genetically engineered modification of biological molecules, pharmaceutical companies are focusing on developing technologies for new delivery systems for existing active pharmaceutical ingredients to improve their effectiveness and bioavailability. In situ systems for intranasal delivery, due to increased viscosity and mucoadhesion to the nasal mucosa, allow overcoming mucociliary clearance and ensuring complete absorption and prolonged release of drugs.Text. The article discusses the main advantages of intranasal in situ delivery systems shown in preclinical studies, as well as approaches to the technology of obtaining and standardization of these systems. The results of scientific research in this field over the past 15 years are summarized, the most promising polymers for creating thermoreversible and pH-sensitive compositions are identified, and modern methods for evaluating the sol-gel transition in situ are analyzed.Conclusion. The use of in situ systems for intranasal administration allows providing a high targeting of the delivery of synthetic and biological molecules to the brain. Currently, numerous pharmacokinetic and pharmacodynamic preclinical studies confirm the effectiveness of such systems, as well as their safety. Thermoreversible commercially available and directionally synthesized polymers (poloxamer 407, PLGA, NIPAAm, etc.), as well as chitosan, remain the most popular for the design of in situ delivery systems. In vitro and ex vivo methods with mucosa and artificial nasal fluid are widely used to assess the parameters of in situ gelation, but to increase the reproducibility of the methods and improve the correlation in vitro/in vivo, it is recommended to conduct modeling of the nasal cavity. Developing the technology and methods of screening of intranasal reversible systems will help to get closer to clinical trials and the entry of these delivery systems into the global pharmaceutical market.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42655049","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 : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-147-153
N. Dyakova, A. Slivkin, S. Gaponov, E. A. Bobina, L. A. Shishorina
Introduction. Small-leaved linden flowers are mainly used for aquatic extracts, and their pharmacological benefit is based on water-soluble polysaccharides.Aim. The aim of this study was to investigate the rate of accumulating all reducing sugars in small-leaved linden flowers, collected in agro- and urbo-cenoses of the Voronezh region.Materials and methods. 51 sites were selected for collecting flowers from the small-leaved linden, which is a widespread deciduous tree species in Russia. In order to determine the total level of reducing sugars in the samples, we measured glucose levels using the method described in Pharmacopeia article "Linden Flower". Correlation coefficients were analyzed to examine in detail the effect of the major pollutants (heavy metals and arsenic) on the accumulation of reducing sugars in small-leaved linden flowers.Results and discussion. All analyzed samples of medicinal plant raw materials were benign in terms of their reducing sugar levels. Samples collected in control (protected) areas contained reducing sugar levels 13.31 to 16.89 %, which is 6–8 times more than the lower numerical value established by the Pharmacopoeia article. In the agrocenoses of the region, the concentration of reducing sugars varied from 6.12 to 16.68 %, which is 3–8 times more than the value given in the Pharmacopoeia article. In the urbocenoses of the region, a lower level of reducing sugars was found compared to samples from protected areas (2.35–13.49 %). Correlation coefficients showed a noticeable negative impact of cadmium, chromium, cobalt, copper, zinc, as well as a moderate negative effect of lead and mercury on the accumulation of reducing sugars in the small-leaved linden flowers.Conclusion. The lowest concentrations of reducing sugars were detected in samples harvested along the streets of large cities in the region, and along highways, roads and railways. This suggests that anthropogenic factors might negatively impact the accumulation of reducing sugars in small-leaved linden flowers in these areas. At the same time, it is possible that saccharide complexes might have reacted with heavy metals instead of the complexing agent when levels of reducing sugars in the samples were quantitatively determined. This would have the effect of underrepresenting reducing sugar levels in the raw materials.
{"title":"Accumulation of Reducing Sugars by Small-leaved Linden Flowers (Tilia cordata Miller, 1768) in the Voronezh Region of Russia","authors":"N. Dyakova, A. Slivkin, S. Gaponov, E. A. Bobina, L. A. Shishorina","doi":"10.33380/2305-2066-2021-10-4-147-153","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-147-153","url":null,"abstract":"Introduction. Small-leaved linden flowers are mainly used for aquatic extracts, and their pharmacological benefit is based on water-soluble polysaccharides.Aim. The aim of this study was to investigate the rate of accumulating all reducing sugars in small-leaved linden flowers, collected in agro- and urbo-cenoses of the Voronezh region.Materials and methods. 51 sites were selected for collecting flowers from the small-leaved linden, which is a widespread deciduous tree species in Russia. In order to determine the total level of reducing sugars in the samples, we measured glucose levels using the method described in Pharmacopeia article \"Linden Flower\". Correlation coefficients were analyzed to examine in detail the effect of the major pollutants (heavy metals and arsenic) on the accumulation of reducing sugars in small-leaved linden flowers.Results and discussion. All analyzed samples of medicinal plant raw materials were benign in terms of their reducing sugar levels. Samples collected in control (protected) areas contained reducing sugar levels 13.31 to 16.89 %, which is 6–8 times more than the lower numerical value established by the Pharmacopoeia article. In the agrocenoses of the region, the concentration of reducing sugars varied from 6.12 to 16.68 %, which is 3–8 times more than the value given in the Pharmacopoeia article. In the urbocenoses of the region, a lower level of reducing sugars was found compared to samples from protected areas (2.35–13.49 %). Correlation coefficients showed a noticeable negative impact of cadmium, chromium, cobalt, copper, zinc, as well as a moderate negative effect of lead and mercury on the accumulation of reducing sugars in the small-leaved linden flowers.Conclusion. The lowest concentrations of reducing sugars were detected in samples harvested along the streets of large cities in the region, and along highways, roads and railways. This suggests that anthropogenic factors might negatively impact the accumulation of reducing sugars in small-leaved linden flowers in these areas. At the same time, it is possible that saccharide complexes might have reacted with heavy metals instead of the complexing agent when levels of reducing sugars in the samples were quantitatively determined. This would have the effect of underrepresenting reducing sugar levels in the raw materials.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47593606","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 : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-72-80
D. Kuznetsov, A. Mironov, V. Neschislyaev, I. Volkhin, A. М. Korolyuk, E. V. Orlova, A. D. Shilina
Introduction. E. coli strains are the main microorganisms used for the production of a number of important biopharmaceutical products. There are no natural sources of microwave radiation on Earth, as it is absorbed by the upper atmosphere. No one doubts the importance of studying the biological effect of microwave radiation. The number of publications devoted to this problem is growing every year, and new ideas for the use of microwaves in drug production technology are emerging.Aim. Reveal the main effects of microwave irradiation and develop a technology for microwave intensification of E. coli culture growth.Materials and methods. This study presents the results of atomic force microscopy, refractometry, NMR relaxometry, turbidimetry, and lumimetry, demonstrating the possibility of microwave intensification of the cultivation process.Results and discussion. It was found that microwave irradiation leads to changes in the mobility of protons and the adsorption of water molecules on biopolymers and cells. These are the main links in the mechanism of "non-thermal" microwave action. A single microwave irradiation, depending on a number of parameters, can decrease or increase the growth of biomass. Studies of the bioluminescence of the E. coli strain with the lux-operon have shown that the optimal processing conditions do not negatively affect the luciferase production and metabolic activity of cells. Conclusion. The intensification procedure using microwave radiation can be considered a promising method and can provide new ideas for various applications in biotechnology.
{"title":"Basics of the Development of Microwave Intensification of Upstream on the Example of Escherichia coli","authors":"D. Kuznetsov, A. Mironov, V. Neschislyaev, I. Volkhin, A. М. Korolyuk, E. V. Orlova, A. D. Shilina","doi":"10.33380/2305-2066-2021-10-4-72-80","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-72-80","url":null,"abstract":"Introduction. E. coli strains are the main microorganisms used for the production of a number of important biopharmaceutical products. There are no natural sources of microwave radiation on Earth, as it is absorbed by the upper atmosphere. No one doubts the importance of studying the biological effect of microwave radiation. The number of publications devoted to this problem is growing every year, and new ideas for the use of microwaves in drug production technology are emerging.Aim. Reveal the main effects of microwave irradiation and develop a technology for microwave intensification of E. coli culture growth.Materials and methods. This study presents the results of atomic force microscopy, refractometry, NMR relaxometry, turbidimetry, and lumimetry, demonstrating the possibility of microwave intensification of the cultivation process.Results and discussion. It was found that microwave irradiation leads to changes in the mobility of protons and the adsorption of water molecules on biopolymers and cells. These are the main links in the mechanism of \"non-thermal\" microwave action. A single microwave irradiation, depending on a number of parameters, can decrease or increase the growth of biomass. Studies of the bioluminescence of the E. coli strain with the lux-operon have shown that the optimal processing conditions do not negatively affect the luciferase production and metabolic activity of cells. Conclusion. The intensification procedure using microwave radiation can be considered a promising method and can provide new ideas for various applications in biotechnology.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45277342","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 : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-191-196
V. V. Goryachkin, V. A. Smirnov, V. N. Shestakov, R. Abramovich
Introduction. The article is devoted to the aspects of improving methodological approaches to the creation of a pharmaceutical quality system (PQS) at enterprises for the production of medicines, taking into account the possibility of using tools and means of digitalization. The relevance of the study is associated with the enduring importance of comprehensive high quality assurance in the development, production and release of medicines into circulation. The implementation of PQS requires numerous transformations of management and production processes, which can be facilitated by tools and elements of digitalization.Aim. To consider the potential and specific areas of application of digital technologies to improve the methodology and practice of developing and implementing PQS.Materials and methods. The state in the subject area was assessed on the basis of the results of economic and statistical analysis and forecasting of the implementation of PQS at Russian pharmaceutical enterprises that have positive and comparatively long experience in this area: the companies LLC "OZON" and JSC "AKRIKHIN". The assessment was carried out by calculating the integral indicator of the effectiveness of the functioning of PQS, which is a set of weighted key performance indicators (KPI) for quality.Results and discussion. The importance of the introduction of PQS for the development of pharmaceutical enterprises and the presence of numerous difficulties in the implementation of PQS, which necessitates the improvement of methodological approaches in the subject area, are stated. It has been proven that even at those enterprises where PQS has been introduced with varying degrees of success, the use of digitalization tools would contribute to a faster, more systematic and high-quality implementation of PQS. Among the key areas of application of digital tools, the authors propose monitoring of quality indicators (using neural network cards) and the use of blockchain platforms and smart contracts to register the release of drugs of appropriate quality.Conclusion. Digital tools contribute to complex improvement in many areas of socio-economic activity. Their active use at pharmaceutical enterprises is intended to contribute to ensuring the proper implementation and uninterrupted functioning of pharmaceutical quality systems, through constant monitoring of the quality of manufactured products and registration of manufactured batches in high-precision information storage systems.
{"title":"The Use of Digital Technologies for the Purpose of Improving Methodological Approaches to the Creation of a Pharmaceutical Quality System at Enterprises for the Production of Medicines","authors":"V. V. Goryachkin, V. A. Smirnov, V. N. Shestakov, R. Abramovich","doi":"10.33380/2305-2066-2021-10-4-191-196","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-191-196","url":null,"abstract":"Introduction. The article is devoted to the aspects of improving methodological approaches to the creation of a pharmaceutical quality system (PQS) at enterprises for the production of medicines, taking into account the possibility of using tools and means of digitalization. The relevance of the study is associated with the enduring importance of comprehensive high quality assurance in the development, production and release of medicines into circulation. The implementation of PQS requires numerous transformations of management and production processes, which can be facilitated by tools and elements of digitalization.Aim. To consider the potential and specific areas of application of digital technologies to improve the methodology and practice of developing and implementing PQS.Materials and methods. The state in the subject area was assessed on the basis of the results of economic and statistical analysis and forecasting of the implementation of PQS at Russian pharmaceutical enterprises that have positive and comparatively long experience in this area: the companies LLC \"OZON\" and JSC \"AKRIKHIN\". The assessment was carried out by calculating the integral indicator of the effectiveness of the functioning of PQS, which is a set of weighted key performance indicators (KPI) for quality.Results and discussion. The importance of the introduction of PQS for the development of pharmaceutical enterprises and the presence of numerous difficulties in the implementation of PQS, which necessitates the improvement of methodological approaches in the subject area, are stated. It has been proven that even at those enterprises where PQS has been introduced with varying degrees of success, the use of digitalization tools would contribute to a faster, more systematic and high-quality implementation of PQS. Among the key areas of application of digital tools, the authors propose monitoring of quality indicators (using neural network cards) and the use of blockchain platforms and smart contracts to register the release of drugs of appropriate quality.Conclusion. Digital tools contribute to complex improvement in many areas of socio-economic activity. Their active use at pharmaceutical enterprises is intended to contribute to ensuring the proper implementation and uninterrupted functioning of pharmaceutical quality systems, through constant monitoring of the quality of manufactured products and registration of manufactured batches in high-precision information storage systems.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46632633","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 : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-117-127
Н. Порфирьева, И. Семина, Р. И. Мустафин, В. Хуторянский, N. N. Porfiryeva, Irina I. Semina, R. I. Moustafine, Vitaliy V. Khutoryanskiy
Introduction. Intranasal drug delivery from nose-to-brain is one of the promising approaches for the treatment of brain diseases including neurodegenerative diseases, stroke, brain tumors, etc.Text. Delivery of drugs through the nose has a number of advantages, including the rapid onset of a pharmacological effect, the ability to bypass the blood-brain barrier, avoidance of some side effects and fast and non-invasive route of administration. However, the significant disadvantages of this route are rapid elimination of the drug from the surface of the mucosal membrane, poor penetration of the drug through the nasal mucosa, mucociliary clearance and effects of proteolytic enzymes. Currently, to overcome the above limitations, various approaches are used, including the development of delivery systems from nose-to-brain, which are mucoadhesive, mucus-penetrating and gel-forming systems that facilitate the retention or penetration of drugs through the mucosal membranes. At the same time, high-molecular weight compounds play a significant role in the design of these systems. In particular, mucoadhesive systems can be prepared from cationic and anionic polymers. Recent studies have also shown that interpolyelectrolyte complexes also exhibit mucoadhesive properties. An improvement in mucoadhesive properties of polymers can also be achieved by conjugating various functional groups such as thiols, maleimides, acrylates, methacrylates, catechols, etc. Mucus-penetrating systems can be prepared by PEGylation of nanoparticles, as well as functionalization with some poly(2-oxazolines), polyvinyl alcohol, etc. The mucus-penetrating ability of these polymers has been shown in other mucosal membranes in the body. Finally, increased penetration can be achieved by using mucolytic agents in combination with non-ionic surfactants. Another approach to increase the efficiency of drug delivery from nose-to-brain is the use of in situ gelling systems. Initially, this type of formulation exists as a solution; then a phase transition to gel is observed in response to chemical and physical effects. Depending on the external stimulation of the phase transition, thermo-, pH-, ion-reversible and other systems are known. These systems have shown effectiveness for delivery to the brain by intranasal administration.Conclusion. Effective intranasal delivery of drugs and therapeutic agents to the brain can be achieved by using mucoadhesive, mucus-penetrating, gelling systems and/or their combinations.
{"title":"Intranasal Administration as a Route to Deliver Drugs to the Brain (Review)","authors":"Н. Порфирьева, И. Семина, Р. И. Мустафин, В. Хуторянский, N. N. Porfiryeva, Irina I. Semina, R. I. Moustafine, Vitaliy V. Khutoryanskiy","doi":"10.33380/2305-2066-2021-10-4-117-127","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-117-127","url":null,"abstract":"Introduction. Intranasal drug delivery from nose-to-brain is one of the promising approaches for the treatment of brain diseases including neurodegenerative diseases, stroke, brain tumors, etc.Text. Delivery of drugs through the nose has a number of advantages, including the rapid onset of a pharmacological effect, the ability to bypass the blood-brain barrier, avoidance of some side effects and fast and non-invasive route of administration. However, the significant disadvantages of this route are rapid elimination of the drug from the surface of the mucosal membrane, poor penetration of the drug through the nasal mucosa, mucociliary clearance and effects of proteolytic enzymes. Currently, to overcome the above limitations, various approaches are used, including the development of delivery systems from nose-to-brain, which are mucoadhesive, mucus-penetrating and gel-forming systems that facilitate the retention or penetration of drugs through the mucosal membranes. At the same time, high-molecular weight compounds play a significant role in the design of these systems. In particular, mucoadhesive systems can be prepared from cationic and anionic polymers. Recent studies have also shown that interpolyelectrolyte complexes also exhibit mucoadhesive properties. An improvement in mucoadhesive properties of polymers can also be achieved by conjugating various functional groups such as thiols, maleimides, acrylates, methacrylates, catechols, etc. Mucus-penetrating systems can be prepared by PEGylation of nanoparticles, as well as functionalization with some poly(2-oxazolines), polyvinyl alcohol, etc. The mucus-penetrating ability of these polymers has been shown in other mucosal membranes in the body. Finally, increased penetration can be achieved by using mucolytic agents in combination with non-ionic surfactants. Another approach to increase the efficiency of drug delivery from nose-to-brain is the use of in situ gelling systems. Initially, this type of formulation exists as a solution; then a phase transition to gel is observed in response to chemical and physical effects. Depending on the external stimulation of the phase transition, thermo-, pH-, ion-reversible and other systems are known. These systems have shown effectiveness for delivery to the brain by intranasal administration.Conclusion. Effective intranasal delivery of drugs and therapeutic agents to the brain can be achieved by using mucoadhesive, mucus-penetrating, gelling systems and/or their combinations.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42347381","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 : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-81-88
M. Sokol, N. Yabbarov, M. Mollaeva, M. V. Chirkina (Fomicheva), V. Balaban'yan, E. Nikolskaya
Introduction. The use of the anticancer drug paclitaxel is limited due to its high toxicity and lipophilicity. A new polymer composition of paclitaxel has been proposed, which provides targeted transport of the drug into tumor cells and improves its safety.Aim. Method development for preparation of a novel paclitaxel formulation consisting of a conjugate of PLGA nanoparticles with the third domain of alpha-fetoprotein.Materials and methods. The object of this study is paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids, the surface of which is modified with a vector molecule - the recombinant third domain of alpha-fetoprotein. Nanoparticles were obtained by single emulsification method and precipitation. Conjugation with a protein molecule was performed by the carbodiimide method. The analysis of the obtained nanoparticles was carried out using dynamic and electrophoretic light scattering, high performance liquid chromatography, dialysis membrane method.Results and discussion. Synthesis of paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids and its conjugation optimization under varying a wide range of conditions have been carried out. The resulting conjugate had an average diameter of 280 ± 12 nm. The conjugation efficiency was 95 %. The release of paclitaxel from the polymer matrix in the release medium was 65 % in 220 h.Conclusions. A method of obtaining and substantiating the composition of the original nanosized form of paclitaxel is proposed. The possibility of prolonged release of paclitaxel from the polymer matrix has been shown.
{"title":"Development of the Composition and Technology for Obtaining Paclitaxel Nanoscale Formulation Consisting of a Conjugate of Polymer Particles with a Protein Vector Molecule","authors":"M. Sokol, N. Yabbarov, M. Mollaeva, M. V. Chirkina (Fomicheva), V. Balaban'yan, E. Nikolskaya","doi":"10.33380/2305-2066-2021-10-4-81-88","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-81-88","url":null,"abstract":"Introduction. The use of the anticancer drug paclitaxel is limited due to its high toxicity and lipophilicity. A new polymer composition of paclitaxel has been proposed, which provides targeted transport of the drug into tumor cells and improves its safety.Aim. Method development for preparation of a novel paclitaxel formulation consisting of a conjugate of PLGA nanoparticles with the third domain of alpha-fetoprotein.Materials and methods. The object of this study is paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids, the surface of which is modified with a vector molecule - the recombinant third domain of alpha-fetoprotein. Nanoparticles were obtained by single emulsification method and precipitation. Conjugation with a protein molecule was performed by the carbodiimide method. The analysis of the obtained nanoparticles was carried out using dynamic and electrophoretic light scattering, high performance liquid chromatography, dialysis membrane method.Results and discussion. Synthesis of paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids and its conjugation optimization under varying a wide range of conditions have been carried out. The resulting conjugate had an average diameter of 280 ± 12 nm. The conjugation efficiency was 95 %. The release of paclitaxel from the polymer matrix in the release medium was 65 % in 220 h.Conclusions. A method of obtaining and substantiating the composition of the original nanosized form of paclitaxel is proposed. The possibility of prolonged release of paclitaxel from the polymer matrix has been shown.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41557921","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 : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-197-207
D. P. Romodanovsky, D. Goryachev
Introduction. The article discusses the problem of assessing the similarity of the dissolution profiles of two batches of the nebivolol. The use of a generally accepted similarity factor for assessing equivalence is unacceptable in some cases, for example, for drugs with a high variability in the values of the release of the active substance from the formulation. At the same time, at present, there are no generally accepted approaches to comparing the profiles of the dissolution kinetics of drugs, with the exception of the method for assessing the comparability of profiles based on the mathematical calculation of the similarity factor f2, which has certain criteria that limit its application.Aim. To demonstrate alternative methods for assessing the similarity between the dissolution profiles of two drugs using a practical example.Materials and methods. The results of the comparative dissolution test of two series of nebivolol at a dosage of 5 mg. Five model-independent methods for assessing the equivalence of drug dissolution were used. Statistical data processing was performed using Microsoft Excel software.Results and discussion. The paper presents a practical example of using five alternative model-independent methods for assessing the equivalence of the dissolution profile. An example is used to illustrate the proposed equivalence limits and statistical methodology. Also, various approaches to determining the boundaries of equivalence have been proposed to assess the similarity of the dissolution profiles of an active substance.Conclusion. According to the results of the comparative dissolution test of two batches of nebivolol, it was shown that the use of the similarity factor as a criterion for assessing dissolution profiles led to a false positive result. In such cases, the possibility of using alternative methods for assessing the equivalence of dissolution profiles described in the article, or other methods presented in the scientific literature, should be considered, with a justification of their acceptability in each specific case.
{"title":"Alternative Methods for Dissolution Profile Comparison in the Dissolution Test","authors":"D. P. Romodanovsky, D. Goryachev","doi":"10.33380/2305-2066-2021-10-4-197-207","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-197-207","url":null,"abstract":"Introduction. The article discusses the problem of assessing the similarity of the dissolution profiles of two batches of the nebivolol. The use of a generally accepted similarity factor for assessing equivalence is unacceptable in some cases, for example, for drugs with a high variability in the values of the release of the active substance from the formulation. At the same time, at present, there are no generally accepted approaches to comparing the profiles of the dissolution kinetics of drugs, with the exception of the method for assessing the comparability of profiles based on the mathematical calculation of the similarity factor f2, which has certain criteria that limit its application.Aim. To demonstrate alternative methods for assessing the similarity between the dissolution profiles of two drugs using a practical example.Materials and methods. The results of the comparative dissolution test of two series of nebivolol at a dosage of 5 mg. Five model-independent methods for assessing the equivalence of drug dissolution were used. Statistical data processing was performed using Microsoft Excel software.Results and discussion. The paper presents a practical example of using five alternative model-independent methods for assessing the equivalence of the dissolution profile. An example is used to illustrate the proposed equivalence limits and statistical methodology. Also, various approaches to determining the boundaries of equivalence have been proposed to assess the similarity of the dissolution profiles of an active substance.Conclusion. According to the results of the comparative dissolution test of two batches of nebivolol, it was shown that the use of the similarity factor as a criterion for assessing dissolution profiles led to a false positive result. In such cases, the possibility of using alternative methods for assessing the equivalence of dissolution profiles described in the article, or other methods presented in the scientific literature, should be considered, with a justification of their acceptability in each specific case.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":"124 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41282281","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 : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-154-161
В. Максимова, Т. В. Плетенева, М. А. Морозова, Аlla V. Marukhlenko, Тatyana V. Maksimova, Тatyana V. Pleteneva, Мariya А. Morozova
Introduction. The production, standardization and quality control process of various dietary supplements containing chelated zinc requires validated quantitative assessment methods. In this work, we propose an X-ray fluorescence spectroscopy (XRF) technique for determining the zinc content in the composition of coordination compounds using the example of a synthesized chelate complex with methionine.Aim. To synthesize Zn(Met)2 chelate complex, to develop and validate a method for its quantitative analysis using the XRF method.Materials and methods. The synthesized zinc chelate complex was investigated by IR spectroscopy. The XRF method was used to develop a method for quantifying the zinc content in the synthesized complex. We used dry mixtures of zinc sulfate monohydrate and L-methionine (Met) in a molar ratio of Zn to Met – 1 : 1, 1 : 2, 1 : 4, 1 : 8 and 1 : 16 and also aqueous solutions of zinc sulfate and L-methionine in a molar ratio of Zn to Met 1 : 2 with Zn concentrations from 0.5 to 100 mmol/l as calibration standards. Complexometric titration was used as an arbitration method for the quantitative determination of zinc content in the samples under study.Results and discussion. The IR spectrum of chelate complex confirmed the presence of a donor-acceptor bond between Zn2+ and the nitrogen atom of amino group in methionine. The titration results showed chelate compounds have a composition corresponding to the stoichiometric formula Zn(Met)2. XRF analysis of dry standard mixed samples demonstrated the presence of matrix effect, that makes impossible an accurate assessment of zinc content in the chelate compound. According to the XRF spectra of aqueous solutions containing zinc sulfate and methionine in a ratio of 1 : 2 at a zinc concentration of 0.5; 1; 2; 3; 4; 5; 10; 25; 50 and 100 mmol/L, a calibration graph was constructed – the dependence of the fluorescence signal intensity for the Kα line of zinc on the concentration of zinc in the solution (r = 0.9996). The method was evaluated by the following validation parameters: specificity, linearity, correctness, precision, and analytical range. The specificity of the validated method was proven in the presence of copper, iron, and silver.Conclusion. The developed method make it possible to determine with sufficient precision and correctness the content of Zn2+ in its aqueous solutions of inorganic and organic nature by the XRF method in the concentration range from 3 to 100 mmol/l without the influence of the matrix.
{"title":"Development and Validation of Method for the Quantitative Determination of Zinc in its Chelate Complexes Using Energy Dispersive X-ray Fluorescence Spectroscopy","authors":"В. Максимова, Т. В. Плетенева, М. А. Морозова, Аlla V. Marukhlenko, Тatyana V. Maksimova, Тatyana V. Pleteneva, Мariya А. Morozova","doi":"10.33380/2305-2066-2021-10-4-154-161","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-154-161","url":null,"abstract":"Introduction. The production, standardization and quality control process of various dietary supplements containing chelated zinc requires validated quantitative assessment methods. In this work, we propose an X-ray fluorescence spectroscopy (XRF) technique for determining the zinc content in the composition of coordination compounds using the example of a synthesized chelate complex with methionine.Aim. To synthesize Zn(Met)2 chelate complex, to develop and validate a method for its quantitative analysis using the XRF method.Materials and methods. The synthesized zinc chelate complex was investigated by IR spectroscopy. The XRF method was used to develop a method for quantifying the zinc content in the synthesized complex. We used dry mixtures of zinc sulfate monohydrate and L-methionine (Met) in a molar ratio of Zn to Met – 1 : 1, 1 : 2, 1 : 4, 1 : 8 and 1 : 16 and also aqueous solutions of zinc sulfate and L-methionine in a molar ratio of Zn to Met 1 : 2 with Zn concentrations from 0.5 to 100 mmol/l as calibration standards. Complexometric titration was used as an arbitration method for the quantitative determination of zinc content in the samples under study.Results and discussion. The IR spectrum of chelate complex confirmed the presence of a donor-acceptor bond between Zn2+ and the nitrogen atom of amino group in methionine. The titration results showed chelate compounds have a composition corresponding to the stoichiometric formula Zn(Met)2. XRF analysis of dry standard mixed samples demonstrated the presence of matrix effect, that makes impossible an accurate assessment of zinc content in the chelate compound. According to the XRF spectra of aqueous solutions containing zinc sulfate and methionine in a ratio of 1 : 2 at a zinc concentration of 0.5; 1; 2; 3; 4; 5; 10; 25; 50 and 100 mmol/L, a calibration graph was constructed – the dependence of the fluorescence signal intensity for the Kα line of zinc on the concentration of zinc in the solution (r = 0.9996). The method was evaluated by the following validation parameters: specificity, linearity, correctness, precision, and analytical range. The specificity of the validated method was proven in the presence of copper, iron, and silver.Conclusion. The developed method make it possible to determine with sufficient precision and correctness the content of Zn2+ in its aqueous solutions of inorganic and organic nature by the XRF method in the concentration range from 3 to 100 mmol/l without the influence of the matrix.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42402177","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 : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-89-95
E. Molokhova, Y. Sorokina, D. Lipin
Introduction. Phytoecdysteroids are a group of natural compounds related in structure and physiological effect to ecdysone - the hormone of insect molting. Phytoecdisteroids have been found to have an antiflammatory effect, which suggests that they have regenerative properties. The development of a soft dosage form containing phytoecdysteroids is of interest.Aim. Improvement of ointment compositions with phytoecdysteroids by optimizing the composition of base adjuvants.Materials and methods. As an active substance was used Serpisten, containing the sum of phytoecdysteroids, the main of which is 20-hydroxyecdysone and obtained from the leaves of Serratulaecoronatae. Raw materials "Serpukhi crowned leaves" were registered by the Federal Service Rospotrebnadzor (Moscow) for the production of dietary supplements (Gr. No. 77.99.23.3.U.1922.3.08), substance Serpisten (Gr. No. 77.99.23.3.U.1923.3.08. TU 9369-002-15092611-2008). In work were used the excipients allowed for medical use: the monoglycerides distilled, T-2 emulsifier, tween 80, sodium - carboxymethylcellulose, polyvinyl alcohol, hydroxide of aluminum, aero forces, vaseline, oil vaseline, sunflower oil. Optimization of ointment auxiliary substances composition was carried out according to the Greco-Latin 4 x 4 square plan with repeated observations. The concentration of hydrogen ions from aqueous ointments was evaluated as process parameters; acid number; release of serpistene from ointment into agar gel, thermal stability of structure. The structural and mechanical properties of the optimal composition ointment composition were determined on a RV type REOTEST 2.1 rotary viscometer (RHEOTEST Medingen GmbH, Germany). Ointment Bepanten (GP Grenzach Produktions GmbH, Germany) was used as a comparison preparation.Results and discussion. During optimization of the composition of the diphilic ointment with serpistene, was found that the ratio of hydrophobic and hydrophilic phases should be 1 : 1, it is advisable to introduce into the ointment base an emulsifier T-2, aerosil and a mixture of vaseline and vaseline oil in the proportion of 1 : 1. As a result of the carried out studies on the optimization of ointment compositions, the following serpisten ointment composition is proposed: serpisten - 0.02; emulsifier T-2 - 3.0; aerosil - 3.0; vaseline - 23.0; vaseline oil - 23.0; ethyl alcohol 40 % - 1 ml; purified water to 100.0. Comparative analysis of effective viscosity showed that the proposed composition is as close as possible to the Bepanten ointment.Conclusion. A set of technological studies was carried out to optimize the composition of the Serpisten, 0.02 °% ointment on a diphilic basis. The developed composition and technology made it possible to obtain a composition with thermal stability, bring the hydrogen index of the ointment closer to the pH of human skin and achieve the parameters included in the rheological optimum for dermatological ointments (0.34-108 Pa • s).
介绍植物蜕皮甾体是一组在结构和生理作用上与昆虫蜕皮激素蜕皮激素有关的天然化合物。植物蜕皮甾类化合物被发现具有抗炎作用，这表明它们具有再生特性。开发一种含有植物蜕皮甾体的软剂型是令人感兴趣的。目标通过优化基础佐剂的组成，用植物蜕皮甾体改善软膏组合物。材料和方法。Serpisten是一种活性物质，它含有大量的植物蜕皮甾体，其中主要是20羟基蜕皮甾酮，是从Serratulaeconatae的叶子中获得的。原料“Serpukhi冠叶”由俄罗斯联邦服务局（莫斯科）注册，用于生产膳食补充剂（组号77.99.23.3.U.192.3.08），物质Serpisten（组号：77.99.23.3.U.1923.3.08）。TU 9369-002-15092611-2008）。在工作中使用了允许用于医疗的赋形剂：蒸馏的单甘油酯、T-2乳化剂、吐温80、羧甲基纤维素钠、聚乙烯醇、氢氧化铝、空气力、凡士林、油性凡士林、葵花油。根据Greco Latin 4 x 4平方计划，反复观察，优化软膏辅助物质的组成。评估来自含水软膏的氢离子的浓度作为工艺参数；酸值；丝氨酸蛋白酶从软膏中释放到琼脂凝胶中，结构的热稳定性。最佳组合物软膏组合物的结构和机械性能在RV型REOTEST 2.1旋转粘度计（RHOTEST Medingen GmbH，德国）上测定。使用Bepanten软膏（GP Grenzach Produkations GmbH，德国）作为比较制剂。结果和讨论。在用serpistene优化二亲软膏的组成时，发现疏水相和亲水相的比例应为1:1，建议在软膏基质中引入乳化剂T-2、气雾剂以及凡士林和凡士林油的混合物，其比例为1:1。通过对软膏组成的优化研究，提出了以下serpisten软膏组成：serpisten-0.02；乳化剂T-2-3.0；aerosil-3.0；凡士林-23.0；凡士林油-23.0；乙醇40%-1ml；纯化水至100.0。有效粘度的比较分析表明，所提出的组合物尽可能接近Bepanten软膏。结论进行了一系列技术研究，以优化0.02°%的双亲性Serpisten软膏的成分。所开发的组合物和技术使获得具有热稳定性的组合物成为可能，使软膏的氢指数更接近人类皮肤的pH值，并实现皮肤软膏流变学最佳参数（0.34-108Pa•s）。
{"title":"Optimization of the Composition of the Ointment with Phytoecdysteroids Serpisten","authors":"E. Molokhova, Y. Sorokina, D. Lipin","doi":"10.33380/2305-2066-2021-10-4-89-95","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-89-95","url":null,"abstract":"Introduction. Phytoecdysteroids are a group of natural compounds related in structure and physiological effect to ecdysone - the hormone of insect molting. Phytoecdisteroids have been found to have an antiflammatory effect, which suggests that they have regenerative properties. The development of a soft dosage form containing phytoecdysteroids is of interest.Aim. Improvement of ointment compositions with phytoecdysteroids by optimizing the composition of base adjuvants.Materials and methods. As an active substance was used Serpisten, containing the sum of phytoecdysteroids, the main of which is 20-hydroxyecdysone and obtained from the leaves of Serratulaecoronatae. Raw materials \"Serpukhi crowned leaves\" were registered by the Federal Service Rospotrebnadzor (Moscow) for the production of dietary supplements (Gr. No. 77.99.23.3.U.1922.3.08), substance Serpisten (Gr. No. 77.99.23.3.U.1923.3.08. TU 9369-002-15092611-2008). In work were used the excipients allowed for medical use: the monoglycerides distilled, T-2 emulsifier, tween 80, sodium - carboxymethylcellulose, polyvinyl alcohol, hydroxide of aluminum, aero forces, vaseline, oil vaseline, sunflower oil. Optimization of ointment auxiliary substances composition was carried out according to the Greco-Latin 4 x 4 square plan with repeated observations. The concentration of hydrogen ions from aqueous ointments was evaluated as process parameters; acid number; release of serpistene from ointment into agar gel, thermal stability of structure. The structural and mechanical properties of the optimal composition ointment composition were determined on a RV type REOTEST 2.1 rotary viscometer (RHEOTEST Medingen GmbH, Germany). Ointment Bepanten (GP Grenzach Produktions GmbH, Germany) was used as a comparison preparation.Results and discussion. During optimization of the composition of the diphilic ointment with serpistene, was found that the ratio of hydrophobic and hydrophilic phases should be 1 : 1, it is advisable to introduce into the ointment base an emulsifier T-2, aerosil and a mixture of vaseline and vaseline oil in the proportion of 1 : 1. As a result of the carried out studies on the optimization of ointment compositions, the following serpisten ointment composition is proposed: serpisten - 0.02; emulsifier T-2 - 3.0; aerosil - 3.0; vaseline - 23.0; vaseline oil - 23.0; ethyl alcohol 40 % - 1 ml; purified water to 100.0. Comparative analysis of effective viscosity showed that the proposed composition is as close as possible to the Bepanten ointment.Conclusion. A set of technological studies was carried out to optimize the composition of the Serpisten, 0.02 °% ointment on a diphilic basis. The developed composition and technology made it possible to obtain a composition with thermal stability, bring the hydrogen index of the ointment closer to the pH of human skin and achieve the parameters included in the rheological optimum for dermatological ointments (0.34-108 Pa • s).","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43461360","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 : 2021-11-25DOI: 10.33380/2305-2066-2021-10-4-36-45
O. L. Saybel, A. I. Radimich, T. Dargaeva, I. Lupanova, E. V. Ferubko, E. N. Kurmanova, I. A. Martynchik
Introduction. Chicory (Cichorium intybus L.) is widely applied for liver disease treatment by traditional medicine of different countries; as well, it is the object for pharmacological research of hepatoprotective activity. In this regard, the method for obtaining dry extract of wild chicory herb (WCHE) is developed in the All-Russian Research Institute of Medicinal and Aromatic Plants.Aim. Aim of the research is determination of the qualitative composition of phenolic compounds, identification of the substances prevailing in WCHE and conducting pharmacological screening of the extract.Materials and methods. WCHE chemical composition has been explored with HPLC-MS/MS method; the main components were determined quantitatively with HPLC-UF method using single compounds that were isolated by us earlier and identified by NMR spectroscopy. WCHE pharmacological screening of hepatoprotective activity research was involving 50 male rats. Acute toxic hepatitis in animals was induced by a single subcutaneous injection of 50 % oily solution of tetrachloromethane (TCM) at a dosage of 0.4 ml per 100 g body weight. One hour before administration TCM, animals received WCHE at the doses of 100 or 500 mg/kg. 48 hours after TCM administration, the activity of serum enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), as well as the content of total bilirubin were determined for preliminary establishment of pharmacological activity. Pathomorphological studies of rat liver were carried out using histological methods. The liver histological structure was inspected using liver sections stained with hematoxylin and eosin.Results and discussion. The component composition of WCHE is represented by oxycoumarins, hydroxycinnamic acids and flavonoids. The dominant phenolic compounds are esculetin, chicoriin, chicoric, chlorogenic and caftaric acids. It was found under acute experimental toxic hepatitis, that preliminary WCHE administration reduces the toxic TCM effect on liver cells. In animals treated with WCHE at doses both 100 mg/kg and 500 mg/kg body weight, it was observed decreases in ALT activity by 35 % and 45 %, AST by 15 % and 28 %, alkaline phosphatase by 15 % and 21 %; the content of total bilirubin by 20 % and 29 %, respectively, in comparison with similar indicators in the group of animals that were not treated with the extract. The histological study showed that WCHE administration to animals at the doses of 100 and 500 mg/kg reduces dystrophic changes in hepatocytes, this effect is more pronounced at the extract dosage of 500 mg/kg.Conclusion. Main WCHE components are oxycoumarins (esculetin, chicoriin), hydroxycinnamic acids (chicoric, chlorogenic and caftaric). According to the results of screening studies, it was established that WCHE in doses of 100 mg/kg and 500 mg/kg is a promising object for further pharmacological research.
{"title":"Phenolic Compounds and Hepatoprotective Activity of Chicory Herb Extract","authors":"O. L. Saybel, A. I. Radimich, T. Dargaeva, I. Lupanova, E. V. Ferubko, E. N. Kurmanova, I. A. Martynchik","doi":"10.33380/2305-2066-2021-10-4-36-45","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4-36-45","url":null,"abstract":"Introduction. Chicory (Cichorium intybus L.) is widely applied for liver disease treatment by traditional medicine of different countries; as well, it is the object for pharmacological research of hepatoprotective activity. In this regard, the method for obtaining dry extract of wild chicory herb (WCHE) is developed in the All-Russian Research Institute of Medicinal and Aromatic Plants.Aim. Aim of the research is determination of the qualitative composition of phenolic compounds, identification of the substances prevailing in WCHE and conducting pharmacological screening of the extract.Materials and methods. WCHE chemical composition has been explored with HPLC-MS/MS method; the main components were determined quantitatively with HPLC-UF method using single compounds that were isolated by us earlier and identified by NMR spectroscopy. WCHE pharmacological screening of hepatoprotective activity research was involving 50 male rats. Acute toxic hepatitis in animals was induced by a single subcutaneous injection of 50 % oily solution of tetrachloromethane (TCM) at a dosage of 0.4 ml per 100 g body weight. One hour before administration TCM, animals received WCHE at the doses of 100 or 500 mg/kg. 48 hours after TCM administration, the activity of serum enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), as well as the content of total bilirubin were determined for preliminary establishment of pharmacological activity. Pathomorphological studies of rat liver were carried out using histological methods. The liver histological structure was inspected using liver sections stained with hematoxylin and eosin.Results and discussion. The component composition of WCHE is represented by oxycoumarins, hydroxycinnamic acids and flavonoids. The dominant phenolic compounds are esculetin, chicoriin, chicoric, chlorogenic and caftaric acids. It was found under acute experimental toxic hepatitis, that preliminary WCHE administration reduces the toxic TCM effect on liver cells. In animals treated with WCHE at doses both 100 mg/kg and 500 mg/kg body weight, it was observed decreases in ALT activity by 35 % and 45 %, AST by 15 % and 28 %, alkaline phosphatase by 15 % and 21 %; the content of total bilirubin by 20 % and 29 %, respectively, in comparison with similar indicators in the group of animals that were not treated with the extract. The histological study showed that WCHE administration to animals at the doses of 100 and 500 mg/kg reduces dystrophic changes in hepatocytes, this effect is more pronounced at the extract dosage of 500 mg/kg.Conclusion. Main WCHE components are oxycoumarins (esculetin, chicoriin), hydroxycinnamic acids (chicoric, chlorogenic and caftaric). According to the results of screening studies, it was established that WCHE in doses of 100 mg/kg and 500 mg/kg is a promising object for further pharmacological research.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48573682","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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