Pub Date : 2021-12-25DOI: 10.33380/2305-2066-2021-10-4(1)-138-145
Anastasiia O. Ponkratova, A. Whaley, E. V. Zhokhova, E. Bezverkhniaia, V. Luzhanin
Introduction. A number of studies have shown that various genetic and environmental factors can affect the biosynthesis and accumulation of secondary metabolites. In particular, it is known that the local geoclimate, seasonal changes, external conditions such as light, temperature, moisture and soil fertility can affect the chemical composition and, as a result, the therapeutic properties of plants used in the pharmaceutical and food industries. Empetrum nigrum L. is a rich source of various pharmacologically active secondary metabolites – chalcones, dihydrochalcones, bibenzyls, 9,10-dihydrophenanthrenes, flavonoids, and proanthocyanidins. In the scientific literature, there is no data on the variation in the chemical composition of E. nigrum depending on the growing area. The obtained data are necessary for a reasonable choice of the collecting location for the plant, with the aim of its further chemical and pharmacological research for the development of promising drug candidates.Aim. To carry out a comparative analysis of secondary metabolites composition in the aerial parts of Empetrum nigrum growing in different regions of the Russian Federation.Materials and methods. Samples collected in three different areas were used to compare HPLC profiles: sample 1 was collected next to SPCPU nursery garden of medicinal plants (Leningrad region, Vsevolozhsky district, Priozerskoe highway, 38 km) in July 2020, sample 2 was collected on the Kola Peninsula, around the Khibiny mountains in July 2020, sample 3 was collected on the Kamchatka Peninsula, next to Khalaktyrsky beach (Pacific Ocean coast) in July 2020. Extracts were analyzed by analytical high performance liquid chromatography (HPLC) using a Prominence LC-20 device (Shimadzu, Japan) equipped with a diode array detector.Results and discussion. As a result of the research, for the first time, a significant variation in the qualitative chemical composition in the aerial parts of Empetrum nigrum growing in different regions of Russian Federation was established. Sample 3, collected on the Kamchatka Peninsula, in comparison with samples 1 and 2, contain the greatest variety of polar secondary metabolites belonging to the classes of flavonoids, tannins, and phenol carboxylic acids, while in the shoots collected in the Leningrad region, the major metabolites were weakly polar compounds belonging to the classes of chalcones, dihydrochalcones, bibenzyls, and 9,10-dihydrophenanthrenes, and in sample 2, collected in the Khibiny mountains, the lowest qualitative content of secondary metabolites was found. This variation may be caused by various environmental factors (biotic and abiotic).Conclusion. For the first time, the comparison of HPLC profiles of aerial part samples of E. nigrum, collected in different regions of the Russia Federation has been carried out. As a result, significant variations in the secondary metabolites composition of the studied samples were established, depending on the regions and g
{"title":"Comparative phytochemical analysis of the aerial parts of Empetrum nigrum L. samples, collected in various regions of the Russian Federation","authors":"Anastasiia O. Ponkratova, A. Whaley, E. V. Zhokhova, E. Bezverkhniaia, V. Luzhanin","doi":"10.33380/2305-2066-2021-10-4(1)-138-145","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-138-145","url":null,"abstract":"Introduction. A number of studies have shown that various genetic and environmental factors can affect the biosynthesis and accumulation of secondary metabolites. In particular, it is known that the local geoclimate, seasonal changes, external conditions such as light, temperature, moisture and soil fertility can affect the chemical composition and, as a result, the therapeutic properties of plants used in the pharmaceutical and food industries. Empetrum nigrum L. is a rich source of various pharmacologically active secondary metabolites – chalcones, dihydrochalcones, bibenzyls, 9,10-dihydrophenanthrenes, flavonoids, and proanthocyanidins. In the scientific literature, there is no data on the variation in the chemical composition of E. nigrum depending on the growing area. The obtained data are necessary for a reasonable choice of the collecting location for the plant, with the aim of its further chemical and pharmacological research for the development of promising drug candidates.Aim. To carry out a comparative analysis of secondary metabolites composition in the aerial parts of Empetrum nigrum growing in different regions of the Russian Federation.Materials and methods. Samples collected in three different areas were used to compare HPLC profiles: sample 1 was collected next to SPCPU nursery garden of medicinal plants (Leningrad region, Vsevolozhsky district, Priozerskoe highway, 38 km) in July 2020, sample 2 was collected on the Kola Peninsula, around the Khibiny mountains in July 2020, sample 3 was collected on the Kamchatka Peninsula, next to Khalaktyrsky beach (Pacific Ocean coast) in July 2020. Extracts were analyzed by analytical high performance liquid chromatography (HPLC) using a Prominence LC-20 device (Shimadzu, Japan) equipped with a diode array detector.Results and discussion. As a result of the research, for the first time, a significant variation in the qualitative chemical composition in the aerial parts of Empetrum nigrum growing in different regions of Russian Federation was established. Sample 3, collected on the Kamchatka Peninsula, in comparison with samples 1 and 2, contain the greatest variety of polar secondary metabolites belonging to the classes of flavonoids, tannins, and phenol carboxylic acids, while in the shoots collected in the Leningrad region, the major metabolites were weakly polar compounds belonging to the classes of chalcones, dihydrochalcones, bibenzyls, and 9,10-dihydrophenanthrenes, and in sample 2, collected in the Khibiny mountains, the lowest qualitative content of secondary metabolites was found. This variation may be caused by various environmental factors (biotic and abiotic).Conclusion. For the first time, the comparison of HPLC profiles of aerial part samples of E. nigrum, collected in different regions of the Russia Federation has been carried out. As a result, significant variations in the secondary metabolites composition of the studied samples were established, depending on the regions and g","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47015073","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 : 2021-12-24DOI: 10.33380/2305-2066-2021-10-4(1)-69-78
U. V. Nogaeva, Julia M. Kotsur, E. Flisyuk, D. Ivkin, E. D. Semivelichenko, I. A. Titovich, I. Narkevich, V. G. Antonov
Introduction. Osteoarthritis (OA) is the most common joint disease that affects more than 10 % of the world's population. More than 600 000 people are diagnosed for the first time each year, but these data do not reflect the true prevalence of the disease, since not all patients seek help from hospitals [1, 2].Aim. Pharmaceutical development of the composition and technology of a gel based on meloxicam, a purine derivative and an immunomodulating component for the treatment of OA with pharmacological substantiation of the content of active substances.Materials and methods. A combination of three active pharmaceutical substances was studied: a non-steroidal anti-inflammatory drug – meloxicam, a purine derivative and an original immunomodulator M. Sodium alginate, natrozole and xanthan gum were considered as gelling agents. Were identified two technological modes of obtaining a gel base. The concentrations of active substances were selected based on the results of preclinical studies. OA was modeled by the combined administration of 0.1 ml of a mixture of Freund's complete adjuvant with a 10 % talc suspension in isotonic sodium chloride solution in a ratio of 1 : 10 into the hock (tarsus) joint cavity. The criteria for choosing the optimal composition of the gel were the size of the damaged joint, exercise tolerance and the histological picture in comparison with intact and control animals. For quantitative data, sample mean values (M) and standard deviations (SD) were calculated. The results corresponded to the laws of normal distribution, statistical processing was carried out using one-way analysis of variance (One-Way ANOVA) using the GraphPad Prism 8.0.2 software, USA at the level of statistical significance of differences p < 0,05 и p < 0,001.Results and discussion. The composition was developed and the technology of the topical dosage form based on sodium alginate was proposed. Preclinical data indicate that the highest efficacy is achieved when using a formulation containing 3 % purine derivative, 5 % immunomodulator M and 0.5 % meloxicam. The developed composition for the effectiveness of suppressing the symptoms of OA showed results that exceeded the reference drug.Conclusion. An original combined agent for the treatment of OA has been developed. Due to the selected component composition, with greater efficiency, it was possible to reduce the dosage of meloxicam to 0.5 %, and the use of sodium alginate as a gelling agent contributed to the prolongation of the action of the gel and the subsequent reduction in the number of applications.
{"title":"Development of the composition and technology of a combined gel for the treatment of osteoarthritis with a pharmacological rationale for the content of components","authors":"U. V. Nogaeva, Julia M. Kotsur, E. Flisyuk, D. Ivkin, E. D. Semivelichenko, I. A. Titovich, I. Narkevich, V. G. Antonov","doi":"10.33380/2305-2066-2021-10-4(1)-69-78","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-69-78","url":null,"abstract":"Introduction. Osteoarthritis (OA) is the most common joint disease that affects more than 10 % of the world's population. More than 600 000 people are diagnosed for the first time each year, but these data do not reflect the true prevalence of the disease, since not all patients seek help from hospitals [1, 2].Aim. Pharmaceutical development of the composition and technology of a gel based on meloxicam, a purine derivative and an immunomodulating component for the treatment of OA with pharmacological substantiation of the content of active substances.Materials and methods. A combination of three active pharmaceutical substances was studied: a non-steroidal anti-inflammatory drug – meloxicam, a purine derivative and an original immunomodulator M. Sodium alginate, natrozole and xanthan gum were considered as gelling agents. Were identified two technological modes of obtaining a gel base. The concentrations of active substances were selected based on the results of preclinical studies. OA was modeled by the combined administration of 0.1 ml of a mixture of Freund's complete adjuvant with a 10 % talc suspension in isotonic sodium chloride solution in a ratio of 1 : 10 into the hock (tarsus) joint cavity. The criteria for choosing the optimal composition of the gel were the size of the damaged joint, exercise tolerance and the histological picture in comparison with intact and control animals. For quantitative data, sample mean values (M) and standard deviations (SD) were calculated. The results corresponded to the laws of normal distribution, statistical processing was carried out using one-way analysis of variance (One-Way ANOVA) using the GraphPad Prism 8.0.2 software, USA at the level of statistical significance of differences p < 0,05 и p < 0,001.Results and discussion. The composition was developed and the technology of the topical dosage form based on sodium alginate was proposed. Preclinical data indicate that the highest efficacy is achieved when using a formulation containing 3 % purine derivative, 5 % immunomodulator M and 0.5 % meloxicam. The developed composition for the effectiveness of suppressing the symptoms of OA showed results that exceeded the reference drug.Conclusion. An original combined agent for the treatment of OA has been developed. Due to the selected component composition, with greater efficiency, it was possible to reduce the dosage of meloxicam to 0.5 %, and the use of sodium alginate as a gelling agent contributed to the prolongation of the action of the gel and the subsequent reduction in the number of applications.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46844096","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 : 2021-12-24DOI: 10.33380/2305-2066-2021-10-4(1)-108-114
T. A. Bitkina, A. V. Basevich
Introduction. The article presents the development of solutions based on the comenic acid substance. The criteria of the studied compositions that affect their stability during storage are evaluated within the framework of the Quality-by-Design concept. The optimal compositions of comenic acid solutions have been established.Aim. The purpose of the study is to develop solutions based on the comenic acid substance and determine the most stable variants of execution.Materials and methods. The study of comenic acid solutions was carried out by using a laboratory pH meter PB-11-P11 (SARTORIUS, Germany) and a liquid/ion chromatograph "Stayer" ("Akvilon" JSC, Russia).Results and discussion. The study made it possible to determine the most stable compositions of solutions based on the comenic acid substance and to establish optimal indicators of their stability criteria. It was found that solutions of comenic acid are the most stable in the pH range: from 4.0 to 6.0. At the same time, regardless of the studied methods of neutralization of comenic acid, solutions are unstable at concentrations of 25 mg/ml or more.Conclusion. As a result of the study, the optimal compositions of solutions based on the comenic acid substance were determined. A comparative analysis of excipients that increase the solubility of comenic acid in aqueous solvents is performed. The stability criteria of the studied solutions are established and their values for ensuring the stability of the developed drug are determined.
{"title":"Development and study of the stability of comenic acid solutions","authors":"T. A. Bitkina, A. V. Basevich","doi":"10.33380/2305-2066-2021-10-4(1)-108-114","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-108-114","url":null,"abstract":"Introduction. The article presents the development of solutions based on the comenic acid substance. The criteria of the studied compositions that affect their stability during storage are evaluated within the framework of the Quality-by-Design concept. The optimal compositions of comenic acid solutions have been established.Aim. The purpose of the study is to develop solutions based on the comenic acid substance and determine the most stable variants of execution.Materials and methods. The study of comenic acid solutions was carried out by using a laboratory pH meter PB-11-P11 (SARTORIUS, Germany) and a liquid/ion chromatograph \"Stayer\" (\"Akvilon\" JSC, Russia).Results and discussion. The study made it possible to determine the most stable compositions of solutions based on the comenic acid substance and to establish optimal indicators of their stability criteria. It was found that solutions of comenic acid are the most stable in the pH range: from 4.0 to 6.0. At the same time, regardless of the studied methods of neutralization of comenic acid, solutions are unstable at concentrations of 25 mg/ml or more.Conclusion. As a result of the study, the optimal compositions of solutions based on the comenic acid substance were determined. A comparative analysis of excipients that increase the solubility of comenic acid in aqueous solvents is performed. The stability criteria of the studied solutions are established and their values for ensuring the stability of the developed drug are determined.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46401742","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 : 2021-12-24DOI: 10.33380/2305-2066-2021-10-4(1)-63-68
E. Molokhova, E. Ponomareva, Y. Sorokina, I. V. Alekseeva, T. E. Ryumina, V. Novikova, A. L. Golovanenko, E. Berezina, Yu. M. Ladutko
Introduction. Soft gelatin capsules are a promising dosage form comprising essential oils as active agents. Joint research of the staff of the Perm State Pharmaceutical Academy, the Research Institute of Nutrition of the Ministry of Energy and Industry of the Republic of Tajikistan have proposed the composition of gelatin mass for encapsulation by the rotary matrix method. The mechanical and physical-technological parameters required to preserve the strength and elasticity of the capsule shell during the production process and storage are determined.Aim. Study of the rheological properties of gelatin masses based on gelatin of different grades, as well as the migration of essential oils through capsule shells.Materials and methods. Pharmaceutical active substances "Lipovitol" and "Limoneol" obtained in the Republic of Tajikistan were used as active substances introduced into the composition of soft gelatin capsules. Sunflower oil was used as the solvent. Gelatin samples were used to obtain gelatin masses: 1 – Foodchem (China), 2 – Brodnickie Zaklady Zelatyny Sp. zo.o. (Poland), 3 - Italgelatine s.p.a. (Italy), 4 – Ewald-Gelatine GmbH (Germany), 5 – Weishardt International (France); glycerol; sunflower oil. Gelatin mass for manufacturing soft capsules was prepared in a closed reactor. Capsules were prepared on an automatic encapsulation line RJWJ – 115 Soft Gelatin Encapsulator Machine (China). The structural and mechanical properties of soft gelatin masses were determined on a rotary viscometer RV type "Reotest 2" (Germany). The dynamics of the process of migration of essential oils and its components were studied by changing their amount in a capsule by chromato-mass spectrometry method on a chromatograph Varian CP 3800 with a quadrupole mass spectrometer 4000 MS as a detector (USA).Results and discussion. When studying the rheological properties of model compositions, it was found that for all samples of gelatin masses there is a decrease in values of effective viscosity when the shear rate increases, which characterizes the tested samples as a structured dispersion system. Additional studies have shown that the gelatin masses have thixotropic properties. Samples of gelatin masses 3–5 had narrower hysteresis loops, while sample 5 the narrowest, restoration of the structure took place quite quickly. Capsules obtained from gelatin mass 3 and 4 samples had a strong seam and were well cut out of the tape. From the mass of sample 5, high strength ribbons were obtained, a high temperature was required to seal the capsules, in some capsules the seam was not glued on one side, as a result, the capsules were rigid and brittle. As a result of the study, the rheological optimum of the gelatin mass suitable for preparing capsules by a rotary matrix method was determined, which has boundaries in the ranges of shear rates of 0.556–243 s-1 and viscosity ranges of 11.46-5028.76 Pa ⋅ s and shear stress of 2788–2808 Pa developing at these rates. When studying th
{"title":"Experimental substantiation of the composition of gelatin mass for obtaining capsules with essential oils","authors":"E. Molokhova, E. Ponomareva, Y. Sorokina, I. V. Alekseeva, T. E. Ryumina, V. Novikova, A. L. Golovanenko, E. Berezina, Yu. M. Ladutko","doi":"10.33380/2305-2066-2021-10-4(1)-63-68","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-63-68","url":null,"abstract":"Introduction. Soft gelatin capsules are a promising dosage form comprising essential oils as active agents. Joint research of the staff of the Perm State Pharmaceutical Academy, the Research Institute of Nutrition of the Ministry of Energy and Industry of the Republic of Tajikistan have proposed the composition of gelatin mass for encapsulation by the rotary matrix method. The mechanical and physical-technological parameters required to preserve the strength and elasticity of the capsule shell during the production process and storage are determined.Aim. Study of the rheological properties of gelatin masses based on gelatin of different grades, as well as the migration of essential oils through capsule shells.Materials and methods. Pharmaceutical active substances \"Lipovitol\" and \"Limoneol\" obtained in the Republic of Tajikistan were used as active substances introduced into the composition of soft gelatin capsules. Sunflower oil was used as the solvent. Gelatin samples were used to obtain gelatin masses: 1 – Foodchem (China), 2 – Brodnickie Zaklady Zelatyny Sp. zo.o. (Poland), 3 - Italgelatine s.p.a. (Italy), 4 – Ewald-Gelatine GmbH (Germany), 5 – Weishardt International (France); glycerol; sunflower oil. Gelatin mass for manufacturing soft capsules was prepared in a closed reactor. Capsules were prepared on an automatic encapsulation line RJWJ – 115 Soft Gelatin Encapsulator Machine (China). The structural and mechanical properties of soft gelatin masses were determined on a rotary viscometer RV type \"Reotest 2\" (Germany). The dynamics of the process of migration of essential oils and its components were studied by changing their amount in a capsule by chromato-mass spectrometry method on a chromatograph Varian CP 3800 with a quadrupole mass spectrometer 4000 MS as a detector (USA).Results and discussion. When studying the rheological properties of model compositions, it was found that for all samples of gelatin masses there is a decrease in values of effective viscosity when the shear rate increases, which characterizes the tested samples as a structured dispersion system. Additional studies have shown that the gelatin masses have thixotropic properties. Samples of gelatin masses 3–5 had narrower hysteresis loops, while sample 5 the narrowest, restoration of the structure took place quite quickly. Capsules obtained from gelatin mass 3 and 4 samples had a strong seam and were well cut out of the tape. From the mass of sample 5, high strength ribbons were obtained, a high temperature was required to seal the capsules, in some capsules the seam was not glued on one side, as a result, the capsules were rigid and brittle. As a result of the study, the rheological optimum of the gelatin mass suitable for preparing capsules by a rotary matrix method was determined, which has boundaries in the ranges of shear rates of 0.556–243 s-1 and viscosity ranges of 11.46-5028.76 Pa ⋅ s and shear stress of 2788–2808 Pa developing at these rates. When studying th","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43817696","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 : 2021-12-24DOI: 10.33380/2305-2066-2021-10-4(1)-104-107
M. Aroyan, Y. Generalova, I. I. Terninko, I. E. Kaukhova, E. Novikova
Introduction. Substances of plant origin exhibit a variety of pharmacological activity in combination with a relatively low toxicity and frequency of side effects. In this regard, a promising direction is the standardization of substances of plant origin in the development of new herbal medicinal products.Aim. Qualitative and quantitative determination of individual coumarin in a dry extract of Melilotus оfficinalis L.Materials and methods. A dry extract of the Melilotus officinalis L. was used as an object of research. Determination of individual coumarin was carried out by high-performance liquid chromatography.Results and discussion. As a result of the research, coumarin was identified by high performance liquid chromatography based on comparison of retention times of the sample with retention times of a standard sample of coumarin in the sample of dry extract under research. The coumarin contents in the dry extract was 0.642 ± 0.007 %.Conclusion. The data obtained on the qualitative and quantitative content of coumarin in the dry extract of Melilotus оfficinalis L. were used in the development of the draft version specification of quality indicators.
{"title":"Determination of individual coumarin in a dry extract of Melilotus officinalis L.","authors":"M. Aroyan, Y. Generalova, I. I. Terninko, I. E. Kaukhova, E. Novikova","doi":"10.33380/2305-2066-2021-10-4(1)-104-107","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-104-107","url":null,"abstract":"Introduction. Substances of plant origin exhibit a variety of pharmacological activity in combination with a relatively low toxicity and frequency of side effects. In this regard, a promising direction is the standardization of substances of plant origin in the development of new herbal medicinal products.Aim. Qualitative and quantitative determination of individual coumarin in a dry extract of Melilotus оfficinalis L.Materials and methods. A dry extract of the Melilotus officinalis L. was used as an object of research. Determination of individual coumarin was carried out by high-performance liquid chromatography.Results and discussion. As a result of the research, coumarin was identified by high performance liquid chromatography based on comparison of retention times of the sample with retention times of a standard sample of coumarin in the sample of dry extract under research. The coumarin contents in the dry extract was 0.642 ± 0.007 %.Conclusion. The data obtained on the qualitative and quantitative content of coumarin in the dry extract of Melilotus оfficinalis L. were used in the development of the draft version specification of quality indicators.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48808111","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 : 2021-12-24DOI: 10.33380/2305-2066-2021-10-4(1)-95-103
J. Strugar, A. Orlova, M. Povydysh
Introduction. Understanding the mechanisms of accumulation of individual groups of biologically active substances in promising types of plant raw materials and the possibility of predicting them is important for solving fundamental and applied problems of pharmaceuticals. To date, differences have been revealed in the qualitative and quantitative composition of secondary metabolites in the aboveground and underground of Comarum palustre L., however, the issue remains unstudied.Aim. Comparative metabolomic study of the composition of the primary metabolites of the aboveground and underground parts of Comarum palustre L.Materials and methods. The object of the study was the aboveground and underground parts of Comarum palustre L., harvested in the vicinity of the nursery of medicinal plants of the St. Petersburg State Chemical and Pharmaceutical University (Leningrad Region, Vsevolozhsky District, Priozerskoe Highway, 38 km) in 2019 and dried. Metabolomic studies based on GC-MS method was perfomed. A statistical analysis based on the MetaboAnalyst 5.0 platform was used.Results and discussion. Analysis of the chromatograms obtained using the GC-MS method revealed the content of 933 primary metabolites in the aboveground and underground parts of Comarum palustre L., 120 of which were identified. Using a number of statistical methods, 10 metabolites from monosaccharides, acids and alcohols, making the greatest contribution to the manifestation of differences between the studied samples, were identified.Conclusion. The study revealed the relationship between the composition of primary and secondary metabolites in medicinal plant raw materials.
{"title":"Comparative GC-MS analysis of the composition of metabolites of aboveground and underground parts of Comarum palustre L","authors":"J. Strugar, A. Orlova, M. Povydysh","doi":"10.33380/2305-2066-2021-10-4(1)-95-103","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-95-103","url":null,"abstract":"Introduction. Understanding the mechanisms of accumulation of individual groups of biologically active substances in promising types of plant raw materials and the possibility of predicting them is important for solving fundamental and applied problems of pharmaceuticals. To date, differences have been revealed in the qualitative and quantitative composition of secondary metabolites in the aboveground and underground of Comarum palustre L., however, the issue remains unstudied.Aim. Comparative metabolomic study of the composition of the primary metabolites of the aboveground and underground parts of Comarum palustre L.Materials and methods. The object of the study was the aboveground and underground parts of Comarum palustre L., harvested in the vicinity of the nursery of medicinal plants of the St. Petersburg State Chemical and Pharmaceutical University (Leningrad Region, Vsevolozhsky District, Priozerskoe Highway, 38 km) in 2019 and dried. Metabolomic studies based on GC-MS method was perfomed. A statistical analysis based on the MetaboAnalyst 5.0 platform was used.Results and discussion. Analysis of the chromatograms obtained using the GC-MS method revealed the content of 933 primary metabolites in the aboveground and underground parts of Comarum palustre L., 120 of which were identified. Using a number of statistical methods, 10 metabolites from monosaccharides, acids and alcohols, making the greatest contribution to the manifestation of differences between the studied samples, were identified.Conclusion. The study revealed the relationship between the composition of primary and secondary metabolites in medicinal plant raw materials.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45175790","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 : 2021-12-24DOI: 10.33380/2305-2066-2021-10-4(1)-79-87
O. A. Terenteva, K. A. Gusev, V. V. Tikhonova, D. N. Maimistov, G. Shandryuk, E. Flisyuk
Introduction. Arterial hypertension is one of the main risk factors for the development of cardiovascular diseases. Drug treatment of arterial hypertension is associated with a number of difficulties: often requires combination therapy, also a possible change in either dosages or drugs during treatment during the patient's life. Three-dimensional printing allows to create individual medicines on-demand.Aim. Study suitability of Kollidon® VA 64 as a matrix-polymer for the preparation of immediate release ramipril printing tablets.Materials and methods. Substance: ramipril; excipients: Kollidon® VA 64, Kollidon® CL-F, Soluplus®, PEG 1500, sodium carbonate anhydrous, Poloxamer 188, sodium stearyl fumarate, mannitol; reagents: hydrochloric acid, acetonitrile for ultra-HPLC, sodium octanesulfonate for HPLC, orthophosphoric acid 85 %, sodium perchlorate analytical grade, triethylamine, standard: ramipril USP (№1598303). Ramipril filaments were prepared by hot melt extrusion on the extruder Haake™ miniCTW (Thermo Fisher Scientific). The tablets were printed on a hand-made 3D printer. The printlets were studied for friability and hardness. Uniformity and quantitative determination of ramipril and impurities in tablets and filaments were determined by high performance liquid chromatography on a Shimadzu Prominence LC liquid chromatograph. Stability of ramipril was studied on a DSC 3+ Mettler Toledo by differential scanning calorimetry. Also, the stability of ramipril was determined by the Raman spectroscopy on an analytical system ORTES-785TRS-2700.Results and discussion. Ramipril filaments with a diameter of 1.75 mm were obtained by melt extrusion at a temperature of 105 °C. They were homogeneous in quantitative content of the active substance. From the resulting filaments, tablets were printed in five configurations with three filling densities: 30 %, 50 % and 100 %. Degradation of ramipril in filaments and tablets is not observed. The melting point of the selected mixture is lower than the melting point of matrix-polymer. It makes possible to lower the processing temperature. Tablets with 100 % filling provide an immediate release of ramipril.Conclusion. Kollidon® VA 64 is suitable as a matrix-polymer for the development of immediate release ramipril printlets. Kollidon® VA 64 provides the necessary physical and processing properties of the filament required for FDM printing.
{"title":"Three-dimensional printing of ramipril tablets by fused deposition modeling","authors":"O. A. Terenteva, K. A. Gusev, V. V. Tikhonova, D. N. Maimistov, G. Shandryuk, E. Flisyuk","doi":"10.33380/2305-2066-2021-10-4(1)-79-87","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-79-87","url":null,"abstract":"Introduction. Arterial hypertension is one of the main risk factors for the development of cardiovascular diseases. Drug treatment of arterial hypertension is associated with a number of difficulties: often requires combination therapy, also a possible change in either dosages or drugs during treatment during the patient's life. Three-dimensional printing allows to create individual medicines on-demand.Aim. Study suitability of Kollidon® VA 64 as a matrix-polymer for the preparation of immediate release ramipril printing tablets.Materials and methods. Substance: ramipril; excipients: Kollidon® VA 64, Kollidon® CL-F, Soluplus®, PEG 1500, sodium carbonate anhydrous, Poloxamer 188, sodium stearyl fumarate, mannitol; reagents: hydrochloric acid, acetonitrile for ultra-HPLC, sodium octanesulfonate for HPLC, orthophosphoric acid 85 %, sodium perchlorate analytical grade, triethylamine, standard: ramipril USP (№1598303). Ramipril filaments were prepared by hot melt extrusion on the extruder Haake™ miniCTW (Thermo Fisher Scientific). The tablets were printed on a hand-made 3D printer. The printlets were studied for friability and hardness. Uniformity and quantitative determination of ramipril and impurities in tablets and filaments were determined by high performance liquid chromatography on a Shimadzu Prominence LC liquid chromatograph. Stability of ramipril was studied on a DSC 3+ Mettler Toledo by differential scanning calorimetry. Also, the stability of ramipril was determined by the Raman spectroscopy on an analytical system ORTES-785TRS-2700.Results and discussion. Ramipril filaments with a diameter of 1.75 mm were obtained by melt extrusion at a temperature of 105 °C. They were homogeneous in quantitative content of the active substance. From the resulting filaments, tablets were printed in five configurations with three filling densities: 30 %, 50 % and 100 %. Degradation of ramipril in filaments and tablets is not observed. The melting point of the selected mixture is lower than the melting point of matrix-polymer. It makes possible to lower the processing temperature. Tablets with 100 % filling provide an immediate release of ramipril.Conclusion. Kollidon® VA 64 is suitable as a matrix-polymer for the development of immediate release ramipril printlets. Kollidon® VA 64 provides the necessary physical and processing properties of the filament required for FDM printing.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45291885","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 : 2021-12-24DOI: 10.33380/2305-2066-2021-10-4(1)-46-53
I. D. Kasymov, A. V. Basevich
Introduction. The article presents the results of studying the technological properties of individual excipients widely used in the compositions of existing orally dispersed tablets (ODT) for subsequent planning a multifactorial experiment. Samples of excipients were analyzed according to such pharmacopoeial indicators as description, flowability, bulk density, compressibility, fractional composition, solubility in water.Aim. The aim of the work is to create a list and study the technological properties of candidate substances for the role of auxiliary substances in the composition being developed by the ODT.Materials and methods. The technological properties of excipient samples were studied according to the methods of the State Pharmacopoeia of the XIV edition using the flowability tester GTL (ERWEKA, Germany), the bulk density tester SVM 221 (ERWEKA, Germany), the tablet press PGR-10 (LabTools, Russia) and the tablet hardness tester TBH 125 TDP (ERWEKA, Germany).Results and discussion. As a result of the study, experimental data on the technological properties of excipient samples were collected, and the selected samples were compared according to pharmaceutical and technological indicators.Conclusion. In the course of the study, a list of auxiliary substances for the development of the composition of ODT was formed and studies of their technological properties were carried out. The obtained experimental data will allow to develop an optimal matrix of a multifactorial experiment for the development of the composition of ODT and justify the choice of excipients.
{"title":"Study of the technological properties of excipients in the development of the composition of orally dispersible tablets","authors":"I. D. Kasymov, A. V. Basevich","doi":"10.33380/2305-2066-2021-10-4(1)-46-53","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-46-53","url":null,"abstract":"Introduction. The article presents the results of studying the technological properties of individual excipients widely used in the compositions of existing orally dispersed tablets (ODT) for subsequent planning a multifactorial experiment. Samples of excipients were analyzed according to such pharmacopoeial indicators as description, flowability, bulk density, compressibility, fractional composition, solubility in water.Aim. The aim of the work is to create a list and study the technological properties of candidate substances for the role of auxiliary substances in the composition being developed by the ODT.Materials and methods. The technological properties of excipient samples were studied according to the methods of the State Pharmacopoeia of the XIV edition using the flowability tester GTL (ERWEKA, Germany), the bulk density tester SVM 221 (ERWEKA, Germany), the tablet press PGR-10 (LabTools, Russia) and the tablet hardness tester TBH 125 TDP (ERWEKA, Germany).Results and discussion. As a result of the study, experimental data on the technological properties of excipient samples were collected, and the selected samples were compared according to pharmaceutical and technological indicators.Conclusion. In the course of the study, a list of auxiliary substances for the development of the composition of ODT was formed and studies of their technological properties were carried out. The obtained experimental data will allow to develop an optimal matrix of a multifactorial experiment for the development of the composition of ODT and justify the choice of excipients.","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47063804","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 : 2021-12-24DOI: 10.33380/2305-2066-2021-10-4(1)-32-36
A. Turyshev, V. D. Belonogova, A. Orlova, K. O. Sidorov, A. Skornyakova
Introduction. Medicinal plant raw materials are one of the most important sources of herbal remedies used both for the prevention and treatment of a number of diseases [1, 2]. Even with the development of modern science and chemistry, medicinal plant raw materials are widely used in both folk and official medicine. The advantage of medicinal plants is their wide range of biological activity, low toxicity and the possibility of long-term use without significant side effects. Human economic activity has a noticeable negative effect on the condition of wild-growing plants: their stocks are decreasing, and some species disappear altogether. Today, given the high level of development of industry and agriculture, the procurement of raw materials for wild medicinal plants is not always possible. Information on the quantitative assessment of the raw material base of wild medicinal plants in the Middle Urals, the content of biologically active substances in medicinal plant raw materials is partially outdated, which determines the need for their systemic resource study and chemical-pharmacognostic study.Aim. Comprehensive assessment of the state of populations of wild medicinal plants in the Middle Urals.Materials and methods. Determination of stocks of raw materials of the studied species of medicinal plants was carried out on specific thickets according to the generally accepted method. The authenticity of the raw materials was established by a macroscopic method when collecting raw material samples. In the course of the study, samples of medicinal plant materials of 5 types were prepared. The determination and assessment of the main indicators of the good quality of medicinal plant raw materials (the content of active and extractive substances, moisture in the mass upon drying, total ash and ash insoluble in a 10% solution of hydrochloric acid) was carried out according to the methods and requirements of the State Pharmacopoeia of the Russian Federation XIV edition. In the raw materials Artemisiae absinthii herba and Leonuri herba, the amount of extractives was determined by the gravimetric method. The quantitative assessment of the content of essential oil in the samples of Origani vulgaris herba and Tanaceti vulgaris flores was carried out by the method of hydrodistillation. To determine the quantitative content of the sum of flavonoids in Hyperici herba, Artemisiae absinthii herba, Leonuri herba and the sum of flavonoids and phenolcarboxylic acids in Tanaceti vulgaris flores, a spectrophotometric method was used.Results and discussion. In the course of resource and phytochemical studies of representatives of the medicinal flora of the Middle Urals, a comprehensive assessment of the state of populations of wild medicinal plants – sources of medicinal plant raw materials (Origani vulgaris herba, Hyperici herba, Tanaceti vulgaris flores, Artemisiae absinthii herba and Leonuri herba) was carried out. The results are included in the electronic inventory o
{"title":"Medicinal flora of the Middle Urals – a prospective source of obtaining medicines","authors":"A. Turyshev, V. D. Belonogova, A. Orlova, K. O. Sidorov, A. Skornyakova","doi":"10.33380/2305-2066-2021-10-4(1)-32-36","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-32-36","url":null,"abstract":"Introduction. Medicinal plant raw materials are one of the most important sources of herbal remedies used both for the prevention and treatment of a number of diseases [1, 2]. Even with the development of modern science and chemistry, medicinal plant raw materials are widely used in both folk and official medicine. The advantage of medicinal plants is their wide range of biological activity, low toxicity and the possibility of long-term use without significant side effects. Human economic activity has a noticeable negative effect on the condition of wild-growing plants: their stocks are decreasing, and some species disappear altogether. Today, given the high level of development of industry and agriculture, the procurement of raw materials for wild medicinal plants is not always possible. Information on the quantitative assessment of the raw material base of wild medicinal plants in the Middle Urals, the content of biologically active substances in medicinal plant raw materials is partially outdated, which determines the need for their systemic resource study and chemical-pharmacognostic study.Aim. Comprehensive assessment of the state of populations of wild medicinal plants in the Middle Urals.Materials and methods. Determination of stocks of raw materials of the studied species of medicinal plants was carried out on specific thickets according to the generally accepted method. The authenticity of the raw materials was established by a macroscopic method when collecting raw material samples. In the course of the study, samples of medicinal plant materials of 5 types were prepared. The determination and assessment of the main indicators of the good quality of medicinal plant raw materials (the content of active and extractive substances, moisture in the mass upon drying, total ash and ash insoluble in a 10% solution of hydrochloric acid) was carried out according to the methods and requirements of the State Pharmacopoeia of the Russian Federation XIV edition. In the raw materials Artemisiae absinthii herba and Leonuri herba, the amount of extractives was determined by the gravimetric method. The quantitative assessment of the content of essential oil in the samples of Origani vulgaris herba and Tanaceti vulgaris flores was carried out by the method of hydrodistillation. To determine the quantitative content of the sum of flavonoids in Hyperici herba, Artemisiae absinthii herba, Leonuri herba and the sum of flavonoids and phenolcarboxylic acids in Tanaceti vulgaris flores, a spectrophotometric method was used.Results and discussion. In the course of resource and phytochemical studies of representatives of the medicinal flora of the Middle Urals, a comprehensive assessment of the state of populations of wild medicinal plants – sources of medicinal plant raw materials (Origani vulgaris herba, Hyperici herba, Tanaceti vulgaris flores, Artemisiae absinthii herba and Leonuri herba) was carried out. The results are included in the electronic inventory o","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41641611","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 : 2021-12-24DOI: 10.33380/2305-2066-2021-10-4(1)-37-45
O. N. Abrosimova, N. Pivovarova, M. Burakova, T. S. Shebitchenko
Introduction. Treatment and prevention of diseases of the oral mucosa is one of the priority tasks in dentistry. In practice, antibacterial agents are often used in the complex treatment of inflammatory and destructive processes. However, long-term, uncontrolled usage of such drugs leads to numerous complications: drug tolerance, weakening of the therapeutic effect, dysbiosis of the oral cavity and gastrointestinal tract, etc. Therefore, at present, the question of search for alternative to antibiotic therapy remains open. As an alternative, it is necessary considering the usage of effective and safe herbal medicines that are easy to digest, less toxic, practically do not cause side effects and allergic reactions, and have a light regulating and normalizing effect.Aim. The aim of the present study is to develop the composition and technology of effervescent granules for the preparation of a solution for rinsing the oral cavity based on phytosubstances.Materials and methods. Dry extracts were obtained from medicinal plant materials: medicinal sage leaves, medicinal calendula flowers, yarrow herb, medicinal rhizomes and roots and astragalus woolly herb. Sodium carbonate, citric acid, anhydrous, microcrystalline cellulose – 90 (EMCOCEL®90M), povidone (Plasdone™ K-29/32) and calcium stearate were used as auxiliary substances in the granule technology. In laboratory conditions, granules based on phytoextracts were obtained by pressing wet masses. Numerical indicators of medicinal plant raw materials, technological properties of dry extracts and granules, as well as indicators of the quality of granules were determined according to the methods described in the State Pharmacopoeia XIV.Results and discussion. The numerical indicators of medicinal plant raw materials (grinding of raw materials and the content of impurities, total ash in medicinal plant materials and ash insoluble in hydrochloric acid, humidity, content of extractives) were determined and the good quality of the raw materials used in the subsequent stages of drug development was confirmed. Dry extracts from each type of medicinal plant raw materials have been developed and the technological properties of dry extracts have been determined. The composition and technology of effervescent granules by pressing wet masses has been developed. To improve the flowability and reduce the hygroscopicity of the granulated material, microcrystalline cellulose – 90 (EMCOCEL®90M) was used as a filler. To create an effervescent dosage form, citric acid and sodium bicarbonate were added to the granules. The mass for granulation was moistened with a 10% alcohol-water solution of Plasdone™ K-29/32. A draft specification of quality indicators for effervescent granules based on phytoextracts is proposed.Conclusion. In the course of the research work, the numerical indicators of medicinal plant raw materials were determined and its quality was confirmed, which made it possible to use it for further production of
{"title":"Development of Technology and Composition of the Medicinal Product for Oral Cavity Based on Phytosubstances","authors":"O. N. Abrosimova, N. Pivovarova, M. Burakova, T. S. Shebitchenko","doi":"10.33380/2305-2066-2021-10-4(1)-37-45","DOIUrl":"https://doi.org/10.33380/2305-2066-2021-10-4(1)-37-45","url":null,"abstract":"Introduction. Treatment and prevention of diseases of the oral mucosa is one of the priority tasks in dentistry. In practice, antibacterial agents are often used in the complex treatment of inflammatory and destructive processes. However, long-term, uncontrolled usage of such drugs leads to numerous complications: drug tolerance, weakening of the therapeutic effect, dysbiosis of the oral cavity and gastrointestinal tract, etc. Therefore, at present, the question of search for alternative to antibiotic therapy remains open. As an alternative, it is necessary considering the usage of effective and safe herbal medicines that are easy to digest, less toxic, practically do not cause side effects and allergic reactions, and have a light regulating and normalizing effect.Aim. The aim of the present study is to develop the composition and technology of effervescent granules for the preparation of a solution for rinsing the oral cavity based on phytosubstances.Materials and methods. Dry extracts were obtained from medicinal plant materials: medicinal sage leaves, medicinal calendula flowers, yarrow herb, medicinal rhizomes and roots and astragalus woolly herb. Sodium carbonate, citric acid, anhydrous, microcrystalline cellulose – 90 (EMCOCEL®90M), povidone (Plasdone™ K-29/32) and calcium stearate were used as auxiliary substances in the granule technology. In laboratory conditions, granules based on phytoextracts were obtained by pressing wet masses. Numerical indicators of medicinal plant raw materials, technological properties of dry extracts and granules, as well as indicators of the quality of granules were determined according to the methods described in the State Pharmacopoeia XIV.Results and discussion. The numerical indicators of medicinal plant raw materials (grinding of raw materials and the content of impurities, total ash in medicinal plant materials and ash insoluble in hydrochloric acid, humidity, content of extractives) were determined and the good quality of the raw materials used in the subsequent stages of drug development was confirmed. Dry extracts from each type of medicinal plant raw materials have been developed and the technological properties of dry extracts have been determined. The composition and technology of effervescent granules by pressing wet masses has been developed. To improve the flowability and reduce the hygroscopicity of the granulated material, microcrystalline cellulose – 90 (EMCOCEL®90M) was used as a filler. To create an effervescent dosage form, citric acid and sodium bicarbonate were added to the granules. The mass for granulation was moistened with a 10% alcohol-water solution of Plasdone™ K-29/32. A draft specification of quality indicators for effervescent granules based on phytoextracts is proposed.Conclusion. In the course of the research work, the numerical indicators of medicinal plant raw materials were determined and its quality was confirmed, which made it possible to use it for further production of","PeriodicalId":36465,"journal":{"name":"Drug Development and Registration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47170884","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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