{"title":"Erratum: \"Development, Validation and Approbation Analytical Method for the Quantitative Determination of Taurine by HPLC-UV Method in the Test of Comparative Dissolution Kinetics\"","authors":"A. M. Poluyanov, A. Kochug, L. S. Mitrofanova, I. D. Nikitin, O. Y. Vergasov, I. Shohin","doi":"10.33380/2305-2066-2023-12-3-261-263","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-261-263","url":null,"abstract":"Drug development & registration. 2023;12(2):62–72. (In Russ.) https://doi.org/10.33380/2305-2066-2023-12-2-62-72. Published: 25.05.2023.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79584439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.33380/2305-2066-2023-12-3-174-188
N. A. Kovaleva, O. V. Trineeva, A. V. Buzlama, A. Y. Kuznetsov
Introduction. Sea buckthorn leaves are a promising object for the development of new medicinal herbal preparations due to an extensive list of biologically active substances (tannins, flavonoids, organic acids, etc.). However, despite the active study of biologically active substances of buckthorn buckthorn leaves, their use in medicine is limited to obtaining an antiviral drug "Hyporamine" containing a dry purified extract from the leaves of this plant.Aim. The aim of the work is to predict the pharmacological and toxic effects of decoction from buckthorn leaves in silico and to evaluate its anti-inflammatory activity in vivo in preclinical studies.Materials and methods. With the help of the PASS-online Internet resource, the prediction of promising pharmacological and possible toxic effects for the main biologically active substances of the phenolic complex of sea buckthorn leaves in silico was carried out. In preclinical studies in vivo (white outbred conventional male rats, 21 individuals, 210–240 g, 3 groups of 7 individuals each) on a model of formalin paw edema of rats (3.0 % aqueous formalin solution, 0.1 ml subplantarly), the anti-inflammatory activity of decoction of sea buckthorn leaves was evaluated. Animals of the experimental groups were administered: a comparison drug – an infusion of chamomile flowers or a decoction of sea buckthorn leaves at a dose of 10 ml/kg intragastrically daily for 7 days.Results and discussion. The analysis and systematization of data on the most likely pharmacological effects of the main biologically active substances of sea buckthorn leaves in silico using the PASS-online platform allow us to consider the most promising study of anti-inflammatory, hepatoprotective, cardioprotective, antibacterial, antifungal and antiviral activity, which opens up prospects for further preclinical and clinical studies in order to expand the list of indications for the use of extracts from the leaves of sea buckthorn. The prediction of the toxic effects of the main biologically active substances of sea buckthorn leaves showed that the smallest number of probable toxic effects is predicted for narcissin and quercetin, the largest for the substance strictinin I (including neurotoxicity, hematotoxicity, negative effects on the cardiovascular system, gastrointestinal toxicity, reproductive toxicity and carcinogenicity), which requires confirmations in preclinical toxicological studies. In preclinical studies in vivo on a model of rat paw edema, it was proved that a decoction of sea buckthorn leaves with a short-term oral course application of 7 days at a dose of 10 ml/kg (235 mg/kg based on the dry residue), it shows a sufficient anti-inflammatory effect, providing a significant, reliable decrease in the severity of rat paw edema, maximum 3 hours after phlogogen administration by 36.0 % compared with the control, which exceeds the effectiveness of the comparison drug (infusion of chamomile flowers).Conclusion. The main types of
{"title":"Pharmacological Activity of Sea Buckthorn Leaves: In silico and In vivo","authors":"N. A. Kovaleva, O. V. Trineeva, A. V. Buzlama, A. Y. Kuznetsov","doi":"10.33380/2305-2066-2023-12-3-174-188","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-174-188","url":null,"abstract":"Introduction. Sea buckthorn leaves are a promising object for the development of new medicinal herbal preparations due to an extensive list of biologically active substances (tannins, flavonoids, organic acids, etc.). However, despite the active study of biologically active substances of buckthorn buckthorn leaves, their use in medicine is limited to obtaining an antiviral drug \"Hyporamine\" containing a dry purified extract from the leaves of this plant.Aim. The aim of the work is to predict the pharmacological and toxic effects of decoction from buckthorn leaves in silico and to evaluate its anti-inflammatory activity in vivo in preclinical studies.Materials and methods. With the help of the PASS-online Internet resource, the prediction of promising pharmacological and possible toxic effects for the main biologically active substances of the phenolic complex of sea buckthorn leaves in silico was carried out. In preclinical studies in vivo (white outbred conventional male rats, 21 individuals, 210–240 g, 3 groups of 7 individuals each) on a model of formalin paw edema of rats (3.0 % aqueous formalin solution, 0.1 ml subplantarly), the anti-inflammatory activity of decoction of sea buckthorn leaves was evaluated. Animals of the experimental groups were administered: a comparison drug – an infusion of chamomile flowers or a decoction of sea buckthorn leaves at a dose of 10 ml/kg intragastrically daily for 7 days.Results and discussion. The analysis and systematization of data on the most likely pharmacological effects of the main biologically active substances of sea buckthorn leaves in silico using the PASS-online platform allow us to consider the most promising study of anti-inflammatory, hepatoprotective, cardioprotective, antibacterial, antifungal and antiviral activity, which opens up prospects for further preclinical and clinical studies in order to expand the list of indications for the use of extracts from the leaves of sea buckthorn. The prediction of the toxic effects of the main biologically active substances of sea buckthorn leaves showed that the smallest number of probable toxic effects is predicted for narcissin and quercetin, the largest for the substance strictinin I (including neurotoxicity, hematotoxicity, negative effects on the cardiovascular system, gastrointestinal toxicity, reproductive toxicity and carcinogenicity), which requires confirmations in preclinical toxicological studies. In preclinical studies in vivo on a model of rat paw edema, it was proved that a decoction of sea buckthorn leaves with a short-term oral course application of 7 days at a dose of 10 ml/kg (235 mg/kg based on the dry residue), it shows a sufficient anti-inflammatory effect, providing a significant, reliable decrease in the severity of rat paw edema, maximum 3 hours after phlogogen administration by 36.0 % compared with the control, which exceeds the effectiveness of the comparison drug (infusion of chamomile flowers).Conclusion. The main types of","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81331168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-31DOI: 10.33380/2305-2066-2023-12-3-169-173
L. A. Musina, O. R. Shangina, A. Lebedeva, A. Prusakov, A. Yashin, V. S. Ponamarev, V. D. Radnatarov, A. Lunegov
Introduction. It is known that the problem of regeneration of damaged peripheral nerves is one of the leading problems in traumatology and neurosurgery.Aim. Aim of the study is to determine the features of the innervation of facial muscles when using allogeneic biomaterials.Materials and methods. The experiment was performed on Chinchilla rabbits (n = 36). The facial nerve was cut in the animals. In the control group (n = 9), the wound was sewn up, in the 1st experimental group (n = 12), a fragment of their masticatory muscle was sewn together with a neurovascular bundle to the denervated buccal muscle. In the 2nd experimental group (n = 15), dispersed allogeneic biomaterials "Regeneration stimulator" and "Vasculogenesis stimulator" were injected into the muscle junction in the operation zone. Rabbits were withdrawn from the experiment for 10, 30, 60 and 180 days. Tissue pieces from the surgery area were examined by transmission electron microscopy.Results and discussion. In the control and 1st experimental groups, the experiment ended with scarring of the operating area and contracture of facial muscles. In the 2nd experimental group, signs of tissue revascularization and axon germination to the buccal muscle with the restoration of individual neuromuscular synapses were revealed.Conclusion. The use of allogeneic biomaterials in operations to restore damaged peripheral nerves accompanying muscles creates conditions not only for the restoration of muscle fibers, but also the vascular bed, as well as nerve elements with neuromuscular connections.
{"title":"Innervation of Facial Muscles Using an Allogeneic Biomaterial in an Experiment","authors":"L. A. Musina, O. R. Shangina, A. Lebedeva, A. Prusakov, A. Yashin, V. S. Ponamarev, V. D. Radnatarov, A. Lunegov","doi":"10.33380/2305-2066-2023-12-3-169-173","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-169-173","url":null,"abstract":"Introduction. It is known that the problem of regeneration of damaged peripheral nerves is one of the leading problems in traumatology and neurosurgery.Aim. Aim of the study is to determine the features of the innervation of facial muscles when using allogeneic biomaterials.Materials and methods. The experiment was performed on Chinchilla rabbits (n = 36). The facial nerve was cut in the animals. In the control group (n = 9), the wound was sewn up, in the 1st experimental group (n = 12), a fragment of their masticatory muscle was sewn together with a neurovascular bundle to the denervated buccal muscle. In the 2nd experimental group (n = 15), dispersed allogeneic biomaterials \"Regeneration stimulator\" and \"Vasculogenesis stimulator\" were injected into the muscle junction in the operation zone. Rabbits were withdrawn from the experiment for 10, 30, 60 and 180 days. Tissue pieces from the surgery area were examined by transmission electron microscopy.Results and discussion. In the control and 1st experimental groups, the experiment ended with scarring of the operating area and contracture of facial muscles. In the 2nd experimental group, signs of tissue revascularization and axon germination to the buccal muscle with the restoration of individual neuromuscular synapses were revealed.Conclusion. The use of allogeneic biomaterials in operations to restore damaged peripheral nerves accompanying muscles creates conditions not only for the restoration of muscle fibers, but also the vascular bed, as well as nerve elements with neuromuscular connections.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85174355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-31DOI: 10.33380/2305-2066-2023-12-3-151-168
S. S. Milovanov
Introduction. Patient recruitment is one of the main quantitative and qualitative characteristics of a clinical trial. As a quantitative characteristic, the recruitment of patients is, first of all, the final figure necessary to answer the researcher's question; as a qualitative characteristic, the recruitment of patients is a process subject to influence. The recruitment of patients in the center is determined by the rate per month and allows you to gain the statistical power of the protocol, and if the recruitment of patients does not reach the planned capacity, then the capacity may not be gained and this leads to the failure of the clinical trial. Failures in patient recruitment reported in the literature lead to more than 80 % of failed clinical trials of all phases. Patient recruitment as a process is influenced by various factors, and the authors identify recruitment predictors, recruitment facilitators, and barriers to patient recruitment.Aim. To consider the general features and patterns of recruitment of patients in clinical trials on the example of international multicenter clinical trials.Materials and methods. We analyzed the quantitative characteristics of patient recruitment in 4 clinical trials with successful recruitment.Results and discussion. Despite the uniqueness of each protocol, the set of patients has its own patterns common to all clinical studies. It was studied, in particular, that the integrative assessment of the preliminary recruitment of patients by the researcher of the clinical center is not associated with an objective pool of patients and affects the rate of patient recruitment and targeted patient recruitment. We found that the number of clinical centers not recruiting patients in each study is at least 30 % of all centers involved. Three patient recruitment rates have also been identified that need to be considered when planning a clinical trial.Conclusion. We have identified patterns in patient recruitment that will help in planning clinical trials.
{"title":"Patterns of Patient Recruitment in Clinical Studies on the Example of International Multicenter Clinical Studies (IMCTs)","authors":"S. S. Milovanov","doi":"10.33380/2305-2066-2023-12-3-151-168","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-151-168","url":null,"abstract":"Introduction. Patient recruitment is one of the main quantitative and qualitative characteristics of a clinical trial. As a quantitative characteristic, the recruitment of patients is, first of all, the final figure necessary to answer the researcher's question; as a qualitative characteristic, the recruitment of patients is a process subject to influence. The recruitment of patients in the center is determined by the rate per month and allows you to gain the statistical power of the protocol, and if the recruitment of patients does not reach the planned capacity, then the capacity may not be gained and this leads to the failure of the clinical trial. Failures in patient recruitment reported in the literature lead to more than 80 % of failed clinical trials of all phases. Patient recruitment as a process is influenced by various factors, and the authors identify recruitment predictors, recruitment facilitators, and barriers to patient recruitment.Aim. To consider the general features and patterns of recruitment of patients in clinical trials on the example of international multicenter clinical trials.Materials and methods. We analyzed the quantitative characteristics of patient recruitment in 4 clinical trials with successful recruitment.Results and discussion. Despite the uniqueness of each protocol, the set of patients has its own patterns common to all clinical studies. It was studied, in particular, that the integrative assessment of the preliminary recruitment of patients by the researcher of the clinical center is not associated with an objective pool of patients and affects the rate of patient recruitment and targeted patient recruitment. We found that the number of clinical centers not recruiting patients in each study is at least 30 % of all centers involved. Three patient recruitment rates have also been identified that need to be considered when planning a clinical trial.Conclusion. We have identified patterns in patient recruitment that will help in planning clinical trials. ","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83295442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-30DOI: 10.33380/2305-2066-2023-12-3-58-65
T. Kovshova, S. Boiko, M. Merkulova, N. S. Osipova, N. Moiseeva, Ju. A. Malinovskaya, S. Mantrov, S. E. Gelperina
Introduction. One of the promising strategies for the development of injectable formulations of poorly water-soluble drugs is the preparation of their nanosuspensions stabilized with albumin. A well-known example of the successful implementation of this technology is Abraxane® (nanoparticle albumin-bound paclitaxel). In the present study, this approach is used for the development of the injectable formulation of a hydrophobic etoposide prodrug.Aim. Development of the injectable formulation of a novel 4'-О-benzyloxycarbonyl derivative of etoposide (ETP-cbz) based on human serum albumin and evaluation of its cytotoxicity against breast carcinoma cells (BC).Materials and methods. The structure of ETP-cbz was confirmed by NMR spectroscopy and elemental analysis; log P was calculated in silico using Molinspiration Cheminformatics. The ETP-cbz-HSA nanoparticles were prepared by high pressure homogenization. The particle size, size distribution, and disintegration concentration were evaluated by dynamic light scattering (DLS) and atomic force microscopy (AFM). The contents of ETP-cbz and albumin in the formulation were determined by HPLC. The conversion ETP-cbz-HSA to etoposide was studied in a model medium in the presence of esterase. The cytotoxicity of ETP-cbz-HSA compared to etoposide and free ETP-cbz was assessed on BC cells (HBL-100 and MCF-7) using a colorimetric MTT assay.Results and discussion. ETP-cbz exhibited higher hydrophobicity as compared to the etoposide (log P 2.42 vs 0.7, respectively). Due to easy cleavage of the carbonate bond in the presence of esterase, ETP-cbz can be considered an etoposide prodrug. The ETP-cbz-containing HSA nanoparticles prepared by a high-pressure homogenization technique had the particle size of 110 ± 9 nm (DLS) and a low disintegration concentration of 3.0 ± 0.1 μg/mL. The drug content was 1.75 mg/mL. The nanoformulation demonstrated high cytotoxic activity in vitro against MCF-7 and HBL-100 cells that was comparable to the activity of substances etoposide and ETP-cbz.Conclusion. The obtained nanoformulation of etoposide prodrug based on albumin, suitable for injection, showed high cytotoxicity against breast cancer cells in vitro and deserves further study to assess the possibility of its use in breast cancer chemotherapy.
{"title":"Development of Injectable Formulation of 4’-O-benzyloxycarbonyl-etoposide Derivative Based on Human Serum Albumin for the Chemotherapy of Breast Cancer","authors":"T. Kovshova, S. Boiko, M. Merkulova, N. S. Osipova, N. Moiseeva, Ju. A. Malinovskaya, S. Mantrov, S. E. Gelperina","doi":"10.33380/2305-2066-2023-12-3-58-65","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-58-65","url":null,"abstract":"Introduction. One of the promising strategies for the development of injectable formulations of poorly water-soluble drugs is the preparation of their nanosuspensions stabilized with albumin. A well-known example of the successful implementation of this technology is Abraxane® (nanoparticle albumin-bound paclitaxel). In the present study, this approach is used for the development of the injectable formulation of a hydrophobic etoposide prodrug.Aim. Development of the injectable formulation of a novel 4'-О-benzyloxycarbonyl derivative of etoposide (ETP-cbz) based on human serum albumin and evaluation of its cytotoxicity against breast carcinoma cells (BC).Materials and methods. The structure of ETP-cbz was confirmed by NMR spectroscopy and elemental analysis; log P was calculated in silico using Molinspiration Cheminformatics. The ETP-cbz-HSA nanoparticles were prepared by high pressure homogenization. The particle size, size distribution, and disintegration concentration were evaluated by dynamic light scattering (DLS) and atomic force microscopy (AFM). The contents of ETP-cbz and albumin in the formulation were determined by HPLC. The conversion ETP-cbz-HSA to etoposide was studied in a model medium in the presence of esterase. The cytotoxicity of ETP-cbz-HSA compared to etoposide and free ETP-cbz was assessed on BC cells (HBL-100 and MCF-7) using a colorimetric MTT assay.Results and discussion. ETP-cbz exhibited higher hydrophobicity as compared to the etoposide (log P 2.42 vs 0.7, respectively). Due to easy cleavage of the carbonate bond in the presence of esterase, ETP-cbz can be considered an etoposide prodrug. The ETP-cbz-containing HSA nanoparticles prepared by a high-pressure homogenization technique had the particle size of 110 ± 9 nm (DLS) and a low disintegration concentration of 3.0 ± 0.1 μg/mL. The drug content was 1.75 mg/mL. The nanoformulation demonstrated high cytotoxic activity in vitro against MCF-7 and HBL-100 cells that was comparable to the activity of substances etoposide and ETP-cbz.Conclusion. The obtained nanoformulation of etoposide prodrug based on albumin, suitable for injection, showed high cytotoxicity against breast cancer cells in vitro and deserves further study to assess the possibility of its use in breast cancer chemotherapy.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86073945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-30DOI: 10.33380/2305-2066-2023-12-3-111-117
M. B. Ilina, E. V. Sergunova, N. V. Bobkova
Introduction. Expansion of the nomenclature of raw materials, including herbal substances, is one of the tasks of the development of the pharmaceutical industry. As an example of a potential and affordable medicinal plant raw material, we can offer the leaves of European dewberry with a proven anti-inflammatory, hypoglycemic, antimicrobial activity. Medicinal plant – European dewberry (Rubus caesius L.) belongs to the genus Rubus L., which includes many species, often difficult to distinguish between each other. For complete pharmacognostic characteristics of medicinal plant raw materials, microscopic examination is necessary.Aim. To carry out a comparative microscopic analysis of the leaves of R. caesius L., R. allegheniensis Porter and R. nessensis Hall to establish anatomical and diagnostic characters.Materials and methods. Leaf samples were collected on the territory of Moscow and the Moscow region in 2021-2022. Microscopic structures were analyzed using a Leica DM1000 light microscope (Germany) with a 10x/20 eyepiece and 10x/0.25 and 40x/0.65 lenses.Results and discussion. A comparative analysis of the anatomical and diagnostic structures of the leaves of the Rubus caesius L. (European dewberry) and its related species has been carried out. The size and frequency of occurrence per 1 mm2 of simple and glandular hairs and stomata were investigated, the type of stomatal apparatus was established, the shape of epidermal cells and crystalline inclusions in the mesophyll were considered. Conclusion. As a result of the study, differences in the anatomical structures of the leaves of three types of blackberries were revealed. Anatomical and diagnostic characters of Rubus caesius L. leaves have been established, which are indicators of the identification of this raw material, including: the presence of simple one-celled fused at the base trichomes, abundant leaf pubescence (especially on the abaxial epiderm), a large number of stomata (106 ± 37 per 1 mm2), the sinuous shape of epidermal cells, cubic crystals of calcium oxalate in the mesophyll.
{"title":"Comparative Study of Anatomical and Diagnostic Features of the Leaves of the European Dewberry (Rubus caesius L.), Allegheny Blackberry (R. allegheniensis Porter) and European Blackberry (R. nessensis Hall)","authors":"M. B. Ilina, E. V. Sergunova, N. V. Bobkova","doi":"10.33380/2305-2066-2023-12-3-111-117","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-111-117","url":null,"abstract":"Introduction. Expansion of the nomenclature of raw materials, including herbal substances, is one of the tasks of the development of the pharmaceutical industry. As an example of a potential and affordable medicinal plant raw material, we can offer the leaves of European dewberry with a proven anti-inflammatory, hypoglycemic, antimicrobial activity. Medicinal plant – European dewberry (Rubus caesius L.) belongs to the genus Rubus L., which includes many species, often difficult to distinguish between each other. For complete pharmacognostic characteristics of medicinal plant raw materials, microscopic examination is necessary.Aim. To carry out a comparative microscopic analysis of the leaves of R. caesius L., R. allegheniensis Porter and R. nessensis Hall to establish anatomical and diagnostic characters.Materials and methods. Leaf samples were collected on the territory of Moscow and the Moscow region in 2021-2022. Microscopic structures were analyzed using a Leica DM1000 light microscope (Germany) with a 10x/20 eyepiece and 10x/0.25 and 40x/0.65 lenses.Results and discussion. A comparative analysis of the anatomical and diagnostic structures of the leaves of the Rubus caesius L. (European dewberry) and its related species has been carried out. The size and frequency of occurrence per 1 mm2 of simple and glandular hairs and stomata were investigated, the type of stomatal apparatus was established, the shape of epidermal cells and crystalline inclusions in the mesophyll were considered. Conclusion. As a result of the study, differences in the anatomical structures of the leaves of three types of blackberries were revealed. Anatomical and diagnostic characters of Rubus caesius L. leaves have been established, which are indicators of the identification of this raw material, including: the presence of simple one-celled fused at the base trichomes, abundant leaf pubescence (especially on the abaxial epiderm), a large number of stomata (106 ± 37 per 1 mm2), the sinuous shape of epidermal cells, cubic crystals of calcium oxalate in the mesophyll.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86054479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-30DOI: 10.33380/2305-2066-2023-12-3-80-88
A. M. Jumabayeva, A. S. Kozhamzharova, L. Ibragimova, I. I. Terninko, E. S. Surbeeva, Z. Sakipova
Introduction. Innovative technologies, new approaches to the creation of medicines, a combination of classic technological methods with the latest trends makes pharmaceutical production a direction with positive dynamics of development. But along with the emergence of new synthetic drugs, as well as biotech products, the use of herbal raw materials for the production of medicines remains relevant. Phytopreparations have a number of undeniable advantages over synthetic drugs and are the drugs of choice in different age groups, including for preventive medicine. The flora of Kazakhstan is distinguished by the presence of endemic plants with a sufficient source of raw materials, which creates the prerequisites for their phytochemical profiling and the subsequent development of phytopreparations. In this regard, Ferula akitschkensis B. Fedtsch. ex Koso-Pol., which is widespread in Kazakhstan, is distinguished by the accumulation of various classes of biologically active substances (flavonoids, coumarins, essential oils) and has experience in folk medicine.Aim. To study the component composition of ethanol extracts of Ferula akitschkensis roots by GC/MS using the Wiley 7th edition, NIST’02 library and to predict the pharmacological activity of identified compounds using the PASS Online web resourceMaterials and methods. Ethanol extraction of roots was obtained by extraction of raw materials with 80 % ethanol in the ratio of raw materials : extractant 1 : 10 and under ultrasonic exposure at a frequency of 15–25 kHz for 10–20 min, followed by separation of the extract from the meal. The obtained extract was analyzed by gas chromatography-mass spectrometry (GC/MS) in full current scanning mode. The obtained mass spectra were interpreted using the Wiley 7th edition and NIST’02 libraries. To predict the biological activity of the identified compounds, the PASS Online web resource was used.Results and discussion. The composition of the ethanol extract of the roots of Ferula akitschkensis B. Fedtsch. ex Koso-Pol. is characterized by a metabolomic profile of compounds that differs from other members of the Ferula genus. Thus, o-cymene, the oxygen derivative of p-cymene – thymol and 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methylphenol accumulate in the roots. These compounds can form a marker profile of the roots of Ferula akitschkensis and be used for species identification within the genus Ferula. The prognostic evaluation of the pharmacological activity of the identified compounds of Ferula akitschkensis showed the presence of an effect on metabolic and biochemical processes, in particular, the creation of a proton potential on the mitochondrial membrane, catalysis, redox processes, and stabilization of cell membranes. In addition, antispasmodic, fibrinolytic, and antioxidant activities can be predicted for the roots of Ferula akitschkensis. And in the focus of creating potential drugs based on the raw materials of this species of Ferula, it is advisable
{"title":"Screening of the Alcohol Fraction of Ferula akitschkensis B. Fedtsch. ex Koso-Pol. by GC/MS Method","authors":"A. M. Jumabayeva, A. S. Kozhamzharova, L. Ibragimova, I. I. Terninko, E. S. Surbeeva, Z. Sakipova","doi":"10.33380/2305-2066-2023-12-3-80-88","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-80-88","url":null,"abstract":"Introduction. Innovative technologies, new approaches to the creation of medicines, a combination of classic technological methods with the latest trends makes pharmaceutical production a direction with positive dynamics of development. But along with the emergence of new synthetic drugs, as well as biotech products, the use of herbal raw materials for the production of medicines remains relevant. Phytopreparations have a number of undeniable advantages over synthetic drugs and are the drugs of choice in different age groups, including for preventive medicine. The flora of Kazakhstan is distinguished by the presence of endemic plants with a sufficient source of raw materials, which creates the prerequisites for their phytochemical profiling and the subsequent development of phytopreparations. In this regard, Ferula akitschkensis B. Fedtsch. ex Koso-Pol., which is widespread in Kazakhstan, is distinguished by the accumulation of various classes of biologically active substances (flavonoids, coumarins, essential oils) and has experience in folk medicine.Aim. To study the component composition of ethanol extracts of Ferula akitschkensis roots by GC/MS using the Wiley 7th edition, NIST’02 library and to predict the pharmacological activity of identified compounds using the PASS Online web resourceMaterials and methods. Ethanol extraction of roots was obtained by extraction of raw materials with 80 % ethanol in the ratio of raw materials : extractant 1 : 10 and under ultrasonic exposure at a frequency of 15–25 kHz for 10–20 min, followed by separation of the extract from the meal. The obtained extract was analyzed by gas chromatography-mass spectrometry (GC/MS) in full current scanning mode. The obtained mass spectra were interpreted using the Wiley 7th edition and NIST’02 libraries. To predict the biological activity of the identified compounds, the PASS Online web resource was used.Results and discussion. The composition of the ethanol extract of the roots of Ferula akitschkensis B. Fedtsch. ex Koso-Pol. is characterized by a metabolomic profile of compounds that differs from other members of the Ferula genus. Thus, o-cymene, the oxygen derivative of p-cymene – thymol and 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methylphenol accumulate in the roots. These compounds can form a marker profile of the roots of Ferula akitschkensis and be used for species identification within the genus Ferula. The prognostic evaluation of the pharmacological activity of the identified compounds of Ferula akitschkensis showed the presence of an effect on metabolic and biochemical processes, in particular, the creation of a proton potential on the mitochondrial membrane, catalysis, redox processes, and stabilization of cell membranes. In addition, antispasmodic, fibrinolytic, and antioxidant activities can be predicted for the roots of Ferula akitschkensis. And in the focus of creating potential drugs based on the raw materials of this species of Ferula, it is advisable ","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81291609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-30DOI: 10.33380/2305-2066-2023-12-3-89-95
T. A. Krol, D. Baleev, V. I. Ossipov
Introduction. Acca sellowiana, or feijoa belongs to the Myrtaceae family and it is an evergreen shrub or small tree 4–6 meters high. The phytochemical composition has been most thoroughly studied in the fruits of A. sellowiana. It has been shown that feijoa is rich in phenolic acids, hydrolysable and condensed tannins, steroidal saponins, and flavonoids. Hydrolysable tannins are known to have high biological activity.Aim. To study the composition and content of hydrolysable tannins in the leaves of A. sellowiana.Materials and methods. Ultra-high performance liquid chromatography coupled with diode array detection and mass spectrometry.Results and discussion. The results obtained showed the presence of 22 phenolic compounds in the extract of the A. sellowiana leaves. They have been classified as flavan-3-ols, flavonoids and hydrolysable tannins. Two compounds could not be identified. The total content of hydrolysable tannins was 44,28 mg/g (90 % of the total phenolic content). At the same time, ellagitannins were the main phenolic compounds of the extract (40,47 mg/g), while the amount of galloyl-glucose was only 3,81 mg/g.Conclusions. Composition and content of hydrolysable tannins in the leaves of A. sellowiana introduced in the greenhouse of VILAR have been studied. The leaves accumulate mainly monomeric ellagitannins represented 92 % of the total content of hydrolysable tannins. The data obtained indicate that the leaves of A. sellowiana can be used as a raw material for obtaining extracts with a high content of ellagitannins and developing drugs based on them.
{"title":"Composition and Content of Hydrolysable Tannins in Feijoa Leaves, Acca sellowiana","authors":"T. A. Krol, D. Baleev, V. I. Ossipov","doi":"10.33380/2305-2066-2023-12-3-89-95","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-89-95","url":null,"abstract":"Introduction. Acca sellowiana, or feijoa belongs to the Myrtaceae family and it is an evergreen shrub or small tree 4–6 meters high. The phytochemical composition has been most thoroughly studied in the fruits of A. sellowiana. It has been shown that feijoa is rich in phenolic acids, hydrolysable and condensed tannins, steroidal saponins, and flavonoids. Hydrolysable tannins are known to have high biological activity.Aim. To study the composition and content of hydrolysable tannins in the leaves of A. sellowiana.Materials and methods. Ultra-high performance liquid chromatography coupled with diode array detection and mass spectrometry.Results and discussion. The results obtained showed the presence of 22 phenolic compounds in the extract of the A. sellowiana leaves. They have been classified as flavan-3-ols, flavonoids and hydrolysable tannins. Two compounds could not be identified. The total content of hydrolysable tannins was 44,28 mg/g (90 % of the total phenolic content). At the same time, ellagitannins were the main phenolic compounds of the extract (40,47 mg/g), while the amount of galloyl-glucose was only 3,81 mg/g.Conclusions. Composition and content of hydrolysable tannins in the leaves of A. sellowiana introduced in the greenhouse of VILAR have been studied. The leaves accumulate mainly monomeric ellagitannins represented 92 % of the total content of hydrolysable tannins. The data obtained indicate that the leaves of A. sellowiana can be used as a raw material for obtaining extracts with a high content of ellagitannins and developing drugs based on them.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"150 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77321965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-30DOI: 10.33380/2305-2066-2023-12-3-49-57
E. Bakhrushina, A. A. Popova, M. V. Pomytkina, M. Anurova, N. Demina, I. Krasnyuk
Introduction. Periprosthetic infections are a major problem in orthopedic surgery. The most optimal way to influence the bacterial film is to suppress the early stages of its formation. The use of hydrogel coatings for the prevention of periprosthetic infections is an effective measure, while the process of coating the implant can be simplified due to the use of in situ systems.Aim. The purpose of the research is to develop and study antibacterial in situ coatings for preoperative treatment of implants.Materials and methods. In the experiment we used poloxamers Kolliphor® P 407 and Kolliphor® P 188 (BASF, Germany), hyaluronic acid high-molecular PrincipHYAL® (1400–1800 kDa), low-molecular PrincipHYAL® (400–600 kDa), mixture of high, medium and low-molecular acids PrincipHYAL® Cube3 (ROELMI HPC Srl, Italy). As screening methods for identifying the optimal composition, we used gelation temperature measurements, pH measurements, studies of rheological properties, and microbiological tests.Results and discussion. During the experiment, we found the optimal concentration of hyaluronic acid 1400–1800 kDa – 0.5 %, at which the studied composition at a temperature of 4.5 ± 0.5 °C was a homogeneous liquid, and it made a sol-gel transition when heated. It was revealed that hyaluronic acid had no significant effect on the gelling temperature, so we added poloxamer 188. We also established the influence of the hyaluronic acid molecular weight on the in situ systems characteristics. High molecular weight hyaluronic acid stabilized the viscosity values and improved the adhesive properties of the system, samples with medium and low molecular weight hyaluronic acid showed lower dynamic viscosity values at the phase gel-sol transition end. We tested the optimal composition (containing 18.0 % poloxamer 407, 2 % poloxamer 188, and 0.5 % hyaluronic acid (1400–1800 kDa) adhesion to the titanium plate. When exposed to the paddle stirrer (rotation speed 20 rpm) for 15 minutes and stored in the thermostat (37,0 ± 0,5 °C) for a week, the analyzed composition showed adhesion strength, which makes it possible to use it for coating.Conclusion. By multistage screening a sample was selected for introduction of a model antibacterial component representing a cocktail of bacteriophages Klebsiella pneumonia, Staphylococcus aureus, Escherichia coli. Microbiological studies showed good compatibility of the immunobiological substance with excipients, which indicated the prospects for further preclinical studies.
{"title":"Development and Study of Antibacterial In situ Coatings for Processing Implants","authors":"E. Bakhrushina, A. A. Popova, M. V. Pomytkina, M. Anurova, N. Demina, I. Krasnyuk","doi":"10.33380/2305-2066-2023-12-3-49-57","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-49-57","url":null,"abstract":"Introduction. Periprosthetic infections are a major problem in orthopedic surgery. The most optimal way to influence the bacterial film is to suppress the early stages of its formation. The use of hydrogel coatings for the prevention of periprosthetic infections is an effective measure, while the process of coating the implant can be simplified due to the use of in situ systems.Aim. The purpose of the research is to develop and study antibacterial in situ coatings for preoperative treatment of implants.Materials and methods. In the experiment we used poloxamers Kolliphor® P 407 and Kolliphor® P 188 (BASF, Germany), hyaluronic acid high-molecular PrincipHYAL® (1400–1800 kDa), low-molecular PrincipHYAL® (400–600 kDa), mixture of high, medium and low-molecular acids PrincipHYAL® Cube3 (ROELMI HPC Srl, Italy). As screening methods for identifying the optimal composition, we used gelation temperature measurements, pH measurements, studies of rheological properties, and microbiological tests.Results and discussion. During the experiment, we found the optimal concentration of hyaluronic acid 1400–1800 kDa – 0.5 %, at which the studied composition at a temperature of 4.5 ± 0.5 °C was a homogeneous liquid, and it made a sol-gel transition when heated. It was revealed that hyaluronic acid had no significant effect on the gelling temperature, so we added poloxamer 188. We also established the influence of the hyaluronic acid molecular weight on the in situ systems characteristics. High molecular weight hyaluronic acid stabilized the viscosity values and improved the adhesive properties of the system, samples with medium and low molecular weight hyaluronic acid showed lower dynamic viscosity values at the phase gel-sol transition end. We tested the optimal composition (containing 18.0 % poloxamer 407, 2 % poloxamer 188, and 0.5 % hyaluronic acid (1400–1800 kDa) adhesion to the titanium plate. When exposed to the paddle stirrer (rotation speed 20 rpm) for 15 minutes and stored in the thermostat (37,0 ± 0,5 °C) for a week, the analyzed composition showed adhesion strength, which makes it possible to use it for coating.Conclusion. By multistage screening a sample was selected for introduction of a model antibacterial component representing a cocktail of bacteriophages Klebsiella pneumonia, Staphylococcus aureus, Escherichia coli. Microbiological studies showed good compatibility of the immunobiological substance with excipients, which indicated the prospects for further preclinical studies.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84328650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-30DOI: 10.33380/2305-2066-2023-12-3-125-133
M. S. Tretyakova, S. Krivoshchekov, E. Plotnikov, E. V. Dorozhko, O. A. Voronova, M. Larkina, K. S. Brazovskiy, M. V. Belousov
Introduction. It was found that in combination with radiation exposure, high doses of lithium salts have a depressing effect on tumor leukemia cells. The selection of the appropriate anionic component makes it possible to obtain pronounced radiosensitizing properties. The lithium salt of gamma-lactone 2,3-dehydro-L-gulonic acid is a promising compound for the creation of radiosensitizing drugs. It was found that this compound exhibits high antioxidant activity among other lithium salts, while showing a pronounced radiosensitizing effect. This radiosensitizing effect is dose-dependent and manifests itself in high concentrations in combination with photon or neutron irradiation. The potential antitumor effect, due to radiosensitization, is realized through the induction of oxidative stress, which implies, first of all, an increase in cytotoxic effects on rapidly proliferating tumor cells. The obtained results provide the necessary basis for the creation of drugs with radiosensitizing activity.Aim. The aim of this work is to conduct an analytical assessment of the content of the active substance and establish the main indicators of the quality of the substance, regulated by the State Pharmacopoeia of the Russian Federation.Materials and methods. During the study, the following parameters were determined: solubility, authenticity, melting point, refractive index, specific rotation, transparency of the solution, color of the solution, pH of the solution, sulfate ash, heavy metals, impurities, water content, residual organic solvents, microbiological purity and a number of others.Results and discussion. A draft specification for the pharmaceutical substance of the lithium salt gamma-lactone 2,3-dehydro-L-gulonic acid has been developed. The optimal parameters for the control of the composition and physico-chemical characteristics and quantitative determination of the pharmaceutical substance have been determined, which is the main task for the pharmaceutical development of the drug. The results obtained make it possible to conduct a comprehensive characterization of the FS and evaluate the quality parameters of the product, which creates the basis for obtaining a dosage form and further studying the properties for creating a drug with a radiosensitizing effect.Conclusion. In the course of the work, experimental samples of the lithium salt gamma-lactone 2,3-dehydro-L-gulonic acid were synthesized and its standardization as a pharmaceutical substance was carried out in accordance with the requirements of the State Pharmacopoeia of the Russian Federation.
{"title":"Standardization of the Pharmaceutical Substance of Lithium Salt Gamma-lactone of 2,3-dehydro-l-gulonic Acid as a Radio-sensitizing Agent","authors":"M. S. Tretyakova, S. Krivoshchekov, E. Plotnikov, E. V. Dorozhko, O. A. Voronova, M. Larkina, K. S. Brazovskiy, M. V. Belousov","doi":"10.33380/2305-2066-2023-12-3-125-133","DOIUrl":"https://doi.org/10.33380/2305-2066-2023-12-3-125-133","url":null,"abstract":"Introduction. It was found that in combination with radiation exposure, high doses of lithium salts have a depressing effect on tumor leukemia cells. The selection of the appropriate anionic component makes it possible to obtain pronounced radiosensitizing properties. The lithium salt of gamma-lactone 2,3-dehydro-L-gulonic acid is a promising compound for the creation of radiosensitizing drugs. It was found that this compound exhibits high antioxidant activity among other lithium salts, while showing a pronounced radiosensitizing effect. This radiosensitizing effect is dose-dependent and manifests itself in high concentrations in combination with photon or neutron irradiation. The potential antitumor effect, due to radiosensitization, is realized through the induction of oxidative stress, which implies, first of all, an increase in cytotoxic effects on rapidly proliferating tumor cells. The obtained results provide the necessary basis for the creation of drugs with radiosensitizing activity.Aim. The aim of this work is to conduct an analytical assessment of the content of the active substance and establish the main indicators of the quality of the substance, regulated by the State Pharmacopoeia of the Russian Federation.Materials and methods. During the study, the following parameters were determined: solubility, authenticity, melting point, refractive index, specific rotation, transparency of the solution, color of the solution, pH of the solution, sulfate ash, heavy metals, impurities, water content, residual organic solvents, microbiological purity and a number of others.Results and discussion. A draft specification for the pharmaceutical substance of the lithium salt gamma-lactone 2,3-dehydro-L-gulonic acid has been developed. The optimal parameters for the control of the composition and physico-chemical characteristics and quantitative determination of the pharmaceutical substance have been determined, which is the main task for the pharmaceutical development of the drug. The results obtained make it possible to conduct a comprehensive characterization of the FS and evaluate the quality parameters of the product, which creates the basis for obtaining a dosage form and further studying the properties for creating a drug with a radiosensitizing effect.Conclusion. In the course of the work, experimental samples of the lithium salt gamma-lactone 2,3-dehydro-L-gulonic acid were synthesized and its standardization as a pharmaceutical substance was carried out in accordance with the requirements of the State Pharmacopoeia of the Russian Federation.","PeriodicalId":11259,"journal":{"name":"Drug development & registration","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91518243","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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