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Age dynamics of strain differences in the morphofunctional state of pancreatic beta- and amylin-producing cells in SHR and Wistar rats SHR和Wistar大鼠胰腺β细胞和淀粉酶分泌细胞形态功能状态的株龄动态差异
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.286820
B. T. A. Hrekova A, Ye. V. Kadzharian, Т. А. Грекова, О. В. Мельнікова, Єлизавета Віталіївна Каджарян
Large-scale epidemiological studies have shown that cardiac pathology and progressive atherosclerosis in patients with diabetes mellitus occurred already at the stage of prediabetes. Obesity and insulin resistance affect cardiometabolic health due to pleiotropic effects of insulin. Despite the vast range of research, some aspects remain hidden links in the overall pathogenesis of metabolic and hemodynamic disorders. The aim of the work was to study the morphofunctional state of pancreatic islets (PIs), beta- and amylin-producing cells in male rats of Wistar strain (normotensive) and SHR (with spontaneous development of hypertension) in age dynamics. Materials and methods. The study was carried out using 38 male Wistar rats and SHRs aged 7 and 24 months. Non-invasive blood pressure (BP) detection procedures were done using the BP-2000 Blood Pressure Analysis System. The morphofunctional state of PIs was examined in serial 5-μm thick pancreatic tissue sections. Beta- and amylin-producing cells were detected after histological preprocessing and the use of monoclonal FITC-conjugated antibodies. Image file processing was done via ImageJ software (National Institutes of Health, USA). Levels of glycemia were monitored with a SUPER GLUCOCARD-II glucometer. Results. SHRs were hyperglycemic both at 7 and at 24 months, 8.41 ± 0.15 mmol/l and 8.90 ± 0.14 mmol/l, respectively, with elevated BP, 155 ± 5 / 80 ± 5 mm Hg and 165 ± 5 / 90 ± 5 mm, respectively. Old SHRs developed PI hypertrophy mainly associated with the increased number and percentage of beta-cells, apparently in response to hyperglycemia. Both in the PIs of adult and old SHRs, the number of amylin-producing cells was lower while the content of amylin was higher than those in the age-matched Wistar rats. Conclusions. Male SHRs are characterized by a persistent increase in blood pressure and abnormalities of carbohydrate metabolism already at adult age, one of the manifestations of which is hyperglycemia worsening with age. Chronic hyperglycemia in SHRs due to the higher insulin requirement finds its expression in low content of this hormone in the islets at adult age and decreased its content in beta-cells in old animals.
大规模流行病学研究表明,糖尿病患者在糖尿病前期就已经出现心脏病变和进行性动脉粥样硬化。肥胖症和胰岛素抵抗会影响心脏代谢健康,这是因为胰岛素具有多重效应。尽管研究范围广泛,但在新陈代谢和血液动力学紊乱的整体发病机制中,某些方面仍是隐性环节。这项工作的目的是研究 Wistar 品系(血压正常)和 SHR(自发性高血压)雄性大鼠胰岛(PIs)、β- 和淀粉酶分泌细胞在年龄动态变化中的形态功能状态。材料和方法。该研究使用了 38 只雄性 Wistar 大鼠和 SHR,年龄分别为 7 个月和 24 个月。使用 BP-2000 血压分析系统进行无创血压检测。在连续的 5μm 厚胰腺组织切片中检测了胰岛素的形态功能状态。经过组织学预处理并使用单克隆 FITC 结合抗体后,可检测到 Beta 和淀粉样蛋白生成细胞。图像文件通过 ImageJ 软件(美国国立卫生研究院)处理。使用 SUPER GLUCOCARD-II 血糖仪监测血糖水平。结果。SHR 在 7 个月和 24 个月时均为高血糖,分别为 8.41 ± 0.15 mmol/l 和 8.90 ± 0.14 mmol/l,同时血压升高,分别为 155 ± 5 / 80 ± 5 mm Hg 和 165 ± 5 / 90 ± 5 mm。老年 SHR 的 PI 肥大主要与β细胞数量和百分比的增加有关,这显然是对高血糖的反应。与年龄匹配的 Wistar 大鼠相比,成年和老年 SHR 的 PI 中产生淀粉酶的细胞数量较少,而淀粉酶含量较高。结论。雄性 SHR 的特点是成年后血压持续升高和碳水化合物代谢异常,其表现之一是高血糖,并随着年龄的增长而加重。由于胰岛素需求量较高,SHR 的慢性高血糖表现为成年动物胰岛中该激素含量较低,而老年动物β细胞中该激素含量降低。
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引用次数: 0
External reference pricing for medicines in Ukraine: latest trends 乌克兰药品的外部参考定价:最新趋势
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.287758
L. Kucherenko, EF I. V. Nizhenkovska A, EF N. V. Sholoiko A, CE L. O. Hala A, CE N. O. Datsiuk A, Л. І. Кучеренко, І. В. Ніженковська, Н. В. Шолойко, Л. О. Гала, Н. О. Дацюк
Compared to the previous year, the share of healthcare expenditure in the state budget of Ukraine has decreased, which is associated with increased funding for the security and defense sector. In terms of gross domestic product, healthcare spending has reduced to 2.8 %, which corresponds to the figures for 2019. These circumstances indicate the importance of proper budget utilization, including effectively regulating medicine prices. One of the key elements of rational healthcare budget usage is the development and implementation of external reference pricing (ERP). A well-formulated and implemented ERP policy for pharmaceuticals contributes to improving patient access to essential medicines (EMs). The aim of this study is to analyze the current status of ERP implementation in Ukraine and provide recommendations for improving this policy. Materials and methods. During the research process, an analysis of the ERP’s current regulatory framework was conducted, and ERP implementation in Ukraine was assessed according to adherence to the 14 best practice principles of ERP proposed by Sullivan, Kanavos & Kalo in 2015. Results. In Ukraine, ERP has been introduced for medicines from the National Essential Medicine Lists (NEML) and the “Affordable Medicines” program. The Ministry of Health (MoH) of Ukraine has approved a Register of marginal wholesale prices for medicines purchased with state budget funds and subject to price regulation. Currently, the register includes 1239 medicinal products, of which 1233 are from NEML and 6 have undergone Health Technology Assessment (HTA). Approximately 58 % of medicines have a set price through ERP, 24 % are regulated by internal reference pricing (IRP), and nearly 18 % have declared prices. This indicates a lack of uniformity in approaches to price regulation for medicines and requires further improvements. According to the latest update of the Register of medicines for reimbursement under the state medical guarantees program, there are 486 medicines, including 72 insulins and 21 immunosuppressive medicines (184 medicines are provided with co-payment). Different approaches, including different reference countries and price calculation algorithms, are applied for the price regulation of medicines in NEML and the “Affordable Medicines” program. An assessment of the implementation of the ERP system in Ukraine based on the 14 best practice principles of ERP proposed by Sullivan, Kanavos & Kalo in 2015 showed that the current policy does not adhere to all principles. Conclusions. The analysis revealed different approaches to pricing for medicines NEML and the “Affordable Medicines” program, indicating the need for harmonizing pricing policies for different lists. The adoption of a unified positive list can contribute to improving pricing policies and efficient resource utilization. Collecting, disseminating, and exchanging data on drug prices is crucial to support transparency in pricing and its control. Regular monitor
与前一年相比,乌克兰国家预算中的医疗支出份额有所下降,这与安全和国防部门的资金增加有关。就国内生产总值而言,医疗保健支出已降至 2.8%,与 2019 年的数字相符。这些情况表明了合理利用预算的重要性,包括有效调节药品价格。合理使用医疗预算的关键因素之一是制定和实施外部参考定价(ERP)。制定和实施完善的药品外部参考定价政策有助于改善患者获得基本药物(EMs)的机会。本研究的目的是分析乌克兰实施外部参考定价的现状,并提出改进这一政策的建议。材料和方法。在研究过程中,对 ERP 现行监管框架进行了分析,并根据 Sullivan、Kanavos & Kalo 于 2015 年提出的 ERP 14 项最佳实践原则,对乌克兰的 ERP 实施情况进行了评估。结果。乌克兰对《国家基本药物目录》(NEML)和 "廉价药物 "计划中的药物实施了ERP。乌克兰卫生部(MoH)已批准了由国家预算资金购买并受价格监管的药品边际批发价格登记册。目前,该登记册包括 1239 种药品,其中 1233 种来自 NEML,6 种经过了卫生技术评估 (HTA)。约 58% 的药品通过企业资源规划(ERP)确定了价格,24% 的药品受内部参考定价(IRP)监管,近 18% 的药品有申报价格。这表明药品价格监管方法缺乏统一性,需要进一步改进。根据最新更新的《国家医疗保障计划报销药品登记册》,共有 486 种药品,其中包括 72 种胰岛素和 21 种免疫抑制剂(184 种药品为自费药品)。在国家医疗保障计划和 "负担得起的药品 "计划中,对药品的价格管理采用了不同的方法,包括不同的参照国和价格计算算法。根据 Sullivan、Kanavos & Kalo 于 2015 年提出的 14 项企业资源规划最佳实践原则,对乌克兰企业资源规划系统的实施情况进行了评估,结果显示现行政策并未遵守所有原则。结论。分析表明,国家药品采购清单和 "负担得起的药品 "计划对药品定价采取了不同的方法,这表明有必要统一不同清单的定价政策。采用统一的肯定列表有助于改进定价政策和提高资源利用效率。收集、传播和交流药品价格数据对于支持定价透明度及其控制至关重要。定期监测市场价格有助于确保定价政策得到遵守,并在出现违规情况时采取适当措施。在乌克兰实施统一的药品定价监管政策是实现欧洲一体化和遵守国际标准的重要一步。
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引用次数: 0
Justification of the choice of excipients during the development of the composition of “Pastinocard” tablets 在开发 "Pastinocard "片剂成分时选择辅料的理由
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.287001
N. А. Symonenko, O. Shpychak, O. Kukhtenko, Ye. A. Bezrukavyi, H. B. Yurieva
The aim of the work is to justify the choice of excipients as components for the cardioprotective medicine “Pastinocard” tablets based on the domestic raw material of cultivated parsnip herb thick extract (CPHTE). Materials and methods. Experimental test samples of mixtures of the plant substance of domestic origin CPHTE with groups of excipients, approved for medical use, were used as the object of research. Results. We conducted experimental research by a mathematical planning method called the Greek–Latin square. In this study, we investigated how 16 different auxiliary substances affected the pharmacotechnological properties of tableting masses and tablets made from PPTEG with cardioprotective properties. Our goal was to determine the optimal composition and manufacturing process for a medication, specifically “Pastinocard” tablets. We also developed project plans for manufacturing regulations and quality control methods, which we successfully tested in the industrial production setting at Pharmaceutical Company “Zdorovye”, LTD in Kharkiv. Conclusions. The formulation for cardioprotective tablets, designated as “Pastinocard”, has been both theoretically justified and experimentally developed by domestic CPHTE raw materials. These research findings have been instrumental in crafting the regulatory documentation for quality control and the production processes of the resulting tablet medication.
这项工作的目的是证明选择辅料作为 "Pastinocard "片剂成分的合理性,该药片是以国产原料栽培香芹草本植物浓提取物(CPHTE)为基础的心脏保护药物。材料和方法研究对象是国产香芹厚朴萃取物与经批准用于医疗用途的各类辅料的混合物试验样品。结果。我们采用一种名为 "希腊-拉丁方阵 "的数学规划方法进行了实验研究。在这项研究中,我们调查了 16 种不同的辅助物质如何影响由具有心脏保护特性的 PPTEG 制成的片剂和药片的药理特性。我们的目标是确定药物(特别是 "Pastinocard "片剂)的最佳成分和生产工艺。我们还制定了生产规范和质量控制方法的项目计划,并在哈尔科夫 "Zdorovye "制药公司的工业生产环境中进行了成功测试。结论名为 "Pastinocard "的心脏保护片剂配方已通过国产 CPHTE 原料的理论论证和实验开发出来。这些研究成果有助于制定质量控制监管文件和由此产生的片剂药物的生产工艺。
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引用次数: 0
On the issue of criminal liability in the national pharmaceutical sector: theoretical foundations and practical aspects 关于国家医药部门的刑事责任问题:理论基础和实践方面
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.285957
O. H. Aleksieiev
A separate segment in the activity of streamlining, stability, and protection of relations arising in the pharmaceutical sphere should be noted the state’s reaction to criminal offenses and, accordingly, the assessment of the actions of persons who commit such offenses. The aim of the work – is to study the current issues of regulatory and legal support of criminal liability in the pharmaceutical sector. Results. The theoretical nature of the criminal responsibility of pharmaceutical workers is revealed from not only legal but also social and moral positions. The legal basis for the status of pharmaceutical workers as distinct subjects of criminal activity is underscored. It has been proven that the object of crimes committed by pharmaceutical workers as a special subject is, first of all, social relations arising in the sphere of human life and health protection; public health (public health); relations arising during the circulation of narcotic drugs, psychotropic substances, and precursors. Differences in terminology defining the object of pharmaceutical crimes are emphasized. Conclusions. The main aspects determining the problem of the qualification of crimes committed in the pharmaceutical sector of the healthcare industry were analyzed. From the standpoint of criminal law theory, the object, subject, objective, and subjective sides of pharmaceutical crimes were characterized.
在理顺、稳定和保护制药领域产生的关系的活动中,应注意国家对刑事犯罪的反应,并相应地对犯有此类罪行的人的行为进行评估。这项工作的目的是研究当前医药领域刑事责任的监管和法律支持问题。结果。不仅从法律角度,而且从社会和道德角度揭示了医药工作者刑事责任的理论性质。强调了医药工作者作为独特的犯罪主体地位的法律依据。事实证明,医药工作者作为特殊主体的犯罪客体首先是在人类生命和健康保护领域产生的社会关系;公共卫生(公共健康);麻醉药品、精神药物和前体流通过程中产生的关系。强调了界定药品犯罪客体的术语差异。结论。分析了决定医疗保健行业制药部门犯罪定性问题的主要方面。从刑法理论的角度,分析了药品犯罪的客体、主体、客观和主观方面的特征。
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引用次数: 0
Development of a method of quantitative determination of the active substance in Angiolin eye drops by the method of high-performance liquid chromatography 高效液相色谱法定量测定安吉林滴眼液中活性物质的方法的开发
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.288356
L. Kucherenko, R. R. Akopian, O. Portna, O. Khromylova, I. Pavliuk
One of the most common eye diseases is a burn injury. Hence, one of the pressing challenges in the field of pharmacy today is the development of new ophthalmic medications, specifically eye drops. Researchers from the Department of Pharmaceutical, Organic, and Bioorganic Chemistry at Zaporizhzhia State Medical and Pharmaceutical University, led by Professor I. A. Mazur, have successfully synthesized a novel compound. This compound is a derivative of 1,2,4-triazole, specifically (S)-2,6-diaminohexanoic acid 3-methyl-1,2,4-triazolyl-5-thioacetate. Notably, this compound demonstrates anti-inflammatory, wound-healing, and reparative activities. The aim of the work is to develop a method of quantitative determination of the active substance in Angiolin eye drops by the method of high-performance liquid chromatography. Materials and methods. The research employed a liquid chromatograph equipped with a UV detector. A column Hypersil ODS C-18 measuring 250 by 4.6 millimeters with a particle size of 5 microns was used. Results. It was determined that the angiolin content in the 1 % eye drops in series 1 falls within the range of 0.985 to 1.010 grams. This indicates that, in terms of the active substance content, the studied series complies with the requirements of the State Pharmacopoeia of Ukraine. Conclusions. As a result of the conducted research, a method for quantitatively determining the active substance in Angiolin eye drops using high-performance liquid chromatography was developed.
烧伤是最常见的眼病之一。因此,当今药学领域面临的紧迫挑战之一就是开发新型眼科药物,特别是眼药水。在 I. A. Mazur 教授的领导下,扎波罗热国立医药大学制药、有机和生物有机化学系的研究人员成功合成了一种新型化合物。这种化合物是 1,2,4-三氮唑的衍生物,特别是 (S)-2,6- 二氨基己酸 3-甲基-1,2,4-三氮唑-5-硫代乙酸酯。值得注意的是,这种化合物具有抗炎、伤口愈合和修复活性。这项工作的目的是开发一种用高效液相色谱法定量测定安吉林滴眼液中活性物质的方法。材料和方法。研究采用了配备紫外检测器的液相色谱仪。色谱柱为 Hypersil ODS C-18,尺寸为 250 x 4.6 毫米,粒径为 5 微米。研究结果经测定,第 1 系列 1 % 滴眼液中的血管黄素含量在 0.985 至 1.010 克之间。这表明,就活性物质含量而言,所研究的系列符合乌克兰国家药典的要求。结论经过研究,我们开发出了一种使用高效液相色谱法定量测定安吉奥林滴眼液中活性物质含量的方法。
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引用次数: 0
The influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents 新型 1,2,3-三唑并-1,4-苯并二氮杂卓衍生物对啮齿动物肌肉张力的影响
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.287999
I. V. Botsula, I. Kireyev, O. Koshovyi, V. Chebanov
Anxiety disorders represent one of the most prevalent categories of psychiatric illnesses, affecting individuals regardless of gender, age, or social standing. They result in substantial personal and societal costs. The pursuit of novel pharmacological approaches for treating these disorders is driven by the increasing medical necessity to enhance the effectiveness and safety profiles of anxiolytic medications. Due to the fact that benzodiazepines and their derivatives have anti-anxiety, hypnotic-sedative, antidepressant, anticonvulsant, and muscle relaxant properties, they occupy a leading place in the treatment of anxiety disorders. An essential aspect of investigating the pharmacological activity of new triazolobenziazepine derivatives is assessing their impact on rodent muscle tone and coordination of movements. The aim of the work is to find out the influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents in the “vertical grid” test and coordination of movements using the rotarod test. Materials and methods. The objects of the study were 5 new derivatives of 1,2,3-triazolo-1,4-benzodiazepines. Before conducting in vivo experiments, these derivatives were mixed with lactose at a ratio of 1:1000. The “vertical grid” test and rotarod test (rotating rod test) were used to reproduce the model of motor behavior of rodents. Results. The presence of a tendency to the manifestation of a myorelaxant effect in the “vertical grid” test was established. The indicator of the total duration of detention at the facilities was similar and did not differ significantly in the control and experimental groups at doses of 0.50 mg/kg and 0.75 mg/kg. Derivatives MA-252, MA-253 and MA-254 at a dose of 1 mg/kg reduced the total duration of retention on the vertical grid, which indicates their mild muscle relaxant effect. In the rotating rod test, MA-253 derivative at a dose of 1 mg/kg increased the retention time on the rotarod, which demonstrates greater physical endurance of the animals of these experimental groups. Conclusions. The study’s findings indicated that the 1,2,3-triazolo-1,4-benzodiazepine derivatives did not exhibit an adverse impact on movement coordination. Some of these derivatives demonstrated a mild muscle relaxant effect. These results support the need for further research into their influence on spontaneous motor activity. Additionally, there’s a necessity to determine the dosage regimen, establish an effective dose, and adapt it for human use.
焦虑症是最常见的精神疾病之一,不分性别、年龄或社会地位都会受到影响。焦虑症造成了巨大的个人和社会损失。为了提高抗焦虑药物的疗效和安全性,医学界越来越需要采用新型药理方法来治疗这些疾病。由于苯二氮卓类药物及其衍生物具有抗焦虑、催眠镇静、抗抑郁、抗惊厥和肌肉松弛的特性,因此在治疗焦虑症方面占据着主导地位。研究新型三唑并氮杂卓衍生物药理活性的一个重要方面是评估它们对啮齿动物肌肉张力和运动协调的影响。本研究的目的是找出新型 1,2,3-三唑并-1,4-苯并二氮杂卓衍生物对啮齿动物在 "垂直网格 "试验中的肌肉张力和使用旋转木马试验的动作协调性的影响。材料和方法研究对象是 1,2,3-三唑并-1,4-苯并二氮杂卓的 5 种新衍生物。在进行体内实验前,这些衍生物与乳糖以 1:1000 的比例混合。实验采用了 "垂直网格 "试验和旋转棒试验(旋转棒试验)来重现啮齿动物的运动行为模型。实验结果在 "垂直网格 "试验中,确定了肌肉松弛效应的存在趋势。在剂量为 0.50 毫克/千克和 0.75 毫克/千克时,对照组和实验组在设施中的总停留时间指标相似,没有显著差异。剂量为 1 毫克/千克的衍生物 MA-252、MA-253 和 MA-254 可缩短在垂直网格上的总滞留时间,这表明它们具有轻微的肌肉松弛作用。在旋转杖测试中,剂量为 1 毫克/千克的 MA-253 衍生物延长了动物在旋转杖上的停留时间,这表明这些实验组的动物具有更强的身体耐力。结论研究结果表明,1,2,3-三唑并-1,4-苯并二氮杂卓衍生物对运动协调性没有不良影响。其中一些衍生物具有轻微的肌肉松弛作用。这些结果表明,有必要进一步研究它们对自发运动活动的影响。此外,还有必要确定剂量方案,确定有效剂量,并使其适合人类使用。
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引用次数: 0
The role and place of the pharmacist-cosmetologist in the choosing and implementation of a cosmetology procedure for hair removal 药剂师-美容师在选择和实施脱毛美容程序中的作用和地位
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.286688
N. Tkachenko, T. Mahanova, H. I. Makurina, N. V. Hrinivetska
In modern cosmetology, the issue of the availability of highly qualified specialists in accordance with the needs of the industry and the implementation of effective cosmetology procedures is acute, which actualizes research on the formation of a patient-centered model of providing medical and pharmaceutical assistance of aesthetic cosmetology. The aim of the work is to substantiate the role and place of the pharmacist-cosmetologist in the selection and provision of a cosmetology procedure for hair removal (CPHR) based on a conjoint analysis of consumer preferences for the specified service. Materials and methods. The main research material for this study included publications by both domestic and foreign scientists concerning aesthetic cosmetology services, consumer behavior regarding cosmetology procedures, professional competencies expected of a pharmacist-cosmetologist, as well as the results of a sociological survey conducted by the CPHR. The research methods employed in this study encompassed information search, synthesis, generalization, formalization, modeling, questionnaires, and regular conjoint analysis. Results. The most attractive methods of epilation were determined – electro epilation, elos epilation and laser epilation. It was established that the majority of consumers do not need a preliminary cosmetologist consultation, but want a consultation after. An algorithm for accompanying CPHR by a pharmacist-cosmetologist was developed. The relevant aspects of pharmaceutical care of CPHR were defined. Conclusions. The conducted conjoint analysis indicates that women are primarily focused on the effectiveness of CPHR (electro epilation, elos epilation, and laser epilation are considered the most effective) and its cost, and then – on the supporting component of the service. The specialist can offer the client (patient) the choice of a method and directly carry out the procedure, having knowledge and experience in diagnosing the condition of the skin and its appendages and understanding the specifics of CPHR against the background of the pharmacoeconomic analysis. The modern Ukrainian model of pharmacist-cosmetologist training allows marketing requirements and accompanying the customer at CPHR. Prospects for further research – formation of an information array and development of pharmaceutical care (assistance) protocols for a pharmacist-cosmetologist in various cosmetic procedures.
在现代美容学中,根据行业需求提供高素质专家和实施有效美容程序的问题十分突出,这就需要研究形成一种以患者为中心的模式,为美容学提供医疗和药物援助。这项工作的目的是在对消费者对特定服务的偏好进行联合分析的基础上,证实药剂师-美容师在选择和提供脱毛美容程序(CPHR)中的作用和地位。材料和方法。本研究的主要研究材料包括国内外科学家发表的有关美容服务、消费者对美容程序的行为、药剂师-美容师应具备的专业能力的出版物,以及 CPHR 进行的社会学调查的结果。本研究采用的研究方法包括信息搜索、综合、概括、形式化、建模、问卷调查和定期联合分析。研究结果确定了最具吸引力的脱毛方法--电脱毛、伊洛斯脱毛和激光脱毛。结果表明,大多数消费者不需要美容师的初步咨询,但希望在咨询后再进行脱毛。药剂师和美容师共同制定了 CPHR 的配套算法。界定了 CPHR 药物护理的相关方面。得出结论。联合分析表明,妇女主要关注 CPHR 的效果(电脱毛、elos 脱毛和激光脱毛被认为是最有效的)和费用,然后才是服务的支持部分。专家可以为客户(病人)提供方法选择并直接实施手术,他们拥有诊断皮肤及其附属物状况的知识和经验,并在药物经济学分析的背景下了解 CPHR 的具体情况。乌克兰的现代药剂师-美容师培训模式允许在 CPHR 中满足营销要求和陪伴客户。进一步研究的前景--形成信息阵列,制定药剂师-美容师在各种美容程序中的药物护理(援助)协议。
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引用次数: 0
Synthesis and analgesic activity of new pyrazole-containing derivatives of 1,2,4-triazole-3-thiol 1,2,4-三唑-3-硫醇的含吡唑新衍生物的合成与镇痛活性
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.288364
S. Fedotov, A. S. Hotsulia, Y. Karpenko
Pain represents a primary symptom of numerous diseases and conditions, affecting millions of people worldwide. Effective analgesic medications can alleviate or eliminate pain, thereby enhancing patients’ quality of life and assisting them in resuming normal physical and social activities. However, several existing analgesics may carry unwanted side effects, such as ulcers, blood clotting issues, drowsiness, and more. The development of new analgesics is focused on creating drugs that are both effective and associated with fewer adverse effects. Considering the continuous rise in the number of patients dealing with neurological, oncological, and other conditions accompanied by chronic pain, there is a growing demand for innovative methods of treatment and pain management. The combination of two different heterocyclic fragments within one molecule makes it possible to use the possibilities of influencing such a molecule on various mechanisms of occurrence and development of various pathological conditions, including those accompanied by pain. Chemical modifications of pyrazole and 1,2,4-triazole structures, involving their incorporation into a single molecule, have the potential, as suggested by in silico predictions, to yield biologically active compounds with analgesic properties. The aim of this work was to determine the optimal conditions for the chemical transformation and properties of 4-amino-5-(3-methylpyrazol-5-yl)-1,2,4-triazole-3-thiol, 4-amino-5-(3-(3-fluorophenyl)pyrazol-5-yl)-1,2,4-triazole-3-thiol and their derivatives for the preparation of bioactive systems with analgesic activity. Materials and methods. The creation of a target series of compounds was implemented by consistently using well-known methods of organic synthesis. 4-Amino-5-(3-methylpyrazole-5-yl)-1,2,4-triazole-3-thiol and 4-amino-5-(3-(3-fluorophenyl)pyrazole-5-yl)-1,2,4-triazole-3-thiol were resynthesized as starting materials using acetone or 1-(3-fluorophenyl)ethane-1-one, diethyloxalate, and sodium methylate using step-by-step hydrazinolysis and carbon disulfide involvement in an alkaline medium. Further targeted functionalization involved the introduction of a 2,6-dichlorophenyl substitute, alkane acid residues, and esters based on them into the structure of the target compounds. The structure of all synthesized substances was determined by IR spectrophotometry, 1H NMR spectroscopy, and elemental analysis. The individuality of the compounds was confirmed by high-performance liquid chromatography-mass spectrometry. The analgesic properties were studied on two models: the “acetic acid-induced writhing test” and a formalin model of pain inflammation. Pharmacokinetic parameters were predictably calculated using the SwissADME online platform. Results. Based on the results of the synthetic part of the work, the structure of 4-amino-5-(3-methylpyrazole-5-yl)-1,2,4-triazole-3-thiol and 4-amino-5-(3-(3-fluorophenyl)pyrazole-5-yl)-1,2,4-triazole-3-thiol, as well as their d
疼痛是多种疾病和病症的主要症状,影响着全球数百万人。有效的镇痛药物可以减轻或消除疼痛,从而提高患者的生活质量,帮助他们恢复正常的身体和社交活动。然而,现有的几种镇痛药可能会带来不必要的副作用,如溃疡、凝血问题、嗜睡等。新型镇痛药的研发重点是创造出既有效又能减少不良反应的药物。考虑到患有神经病、肿瘤和其他疾病并伴有慢性疼痛的患者人数持续上升,对创新治疗和疼痛管理方法的需求日益增长。在一个分子中结合两种不同的杂环片段,可以利用这种分子对各种病症(包括伴有疼痛的病症)的发生和发展机制产生影响的可能性。对吡唑和 1,2,4-三氮唑结构进行化学修饰,将其纳入一个分子中,正如硅学预测所表明的那样,有可能产生具有镇痛特性的生物活性化合物。这项工作的目的是确定 4-氨基-5-(3-甲基吡唑-5-基)-1,2,4-三唑-3-硫醇、4-氨基-5-(3-(3-氟苯基)吡唑-5-基)-1,2,4-三唑-3-硫醇及其衍生物化学转化和特性的最佳条件,以制备具有镇痛活性的生物活性体系。材料和方法。目标系列化合物的制备一直采用众所周知的有机合成方法。以 4-氨基-5-(3-甲基吡唑-5-基)-1,2,4-三唑-3-硫醇和 4-氨基-5-(3-(3-氟苯基)吡唑-5-基)-1,2,4-三唑-3-硫醇为起始原料,在碱性介质中使用丙酮或 1-(3-氟苯基)乙烷-1-酮、二乙醇胺和甲酸钠,通过逐步肼解和二硫化碳参与重新合成。进一步的定向功能化包括在目标化合物的结构中引入 2,6-二氯苯基替代物、烷酸残基和以它们为基础的酯。所有合成物质的结构都是通过红外分光光度法、1H NMR 光谱法和元素分析确定的。通过高效液相色谱-质谱法确认了化合物的独特性。在 "醋酸诱发的蠕动试验 "和福尔马林疼痛炎症模型中研究了化合物的镇痛特性。药代动力学参数通过 SwissADME 在线平台进行预测计算。结果根据合成部分的研究结果,成功再现了 4-氨基-5-(3-甲基吡唑-5-基)-1,2,4-三唑-3-硫醇和 4-氨基-5-(3-(3-氟苯基)吡唑-5-基)-1,2,4-三唑-3-硫醇及其衍生物的结构。事实证明,2,6-二氯苯基替代物以及饱和羧酸片段及其酯类对形成抗痛觉活性有好处。在 ADME 分析过程中确定的药代动力学参数定量指标几乎都在可接受的范围内。结论建立了 4-氨基-5-(3-甲基吡唑-5-基)-1,2,4-三唑-3-硫醇、4-氨基-5-(3-(3-氟苯基)吡唑-5-基)-1,2,4-三唑-3-硫醇合成和结构修饰的最佳条件、从而制备出 2-((4-氨基-5-(3-甲基吡唑-5-基)-1,2,4-三唑-3-基)硫)烷酸及其酯类,以及 [1,2,4]三唑并[3,4-b][1,3,4]噻二嗪系统。研究表明,1,2,4-三唑-3-硫醇的吡唑衍生物与 2,6-二氯苯基取代基以及饱和羧酸及其酯的片段相结合,为形成具有抗痛觉活性的化合物创造了条件,醋酸诱导的蠕动试验和福尔马林炎症模型的实验数据证实了这一点。
{"title":"Synthesis and analgesic activity of new pyrazole-containing derivatives of 1,2,4-triazole-3-thiol","authors":"S. Fedotov, A. S. Hotsulia, Y. Karpenko","doi":"10.14739/2409-2932.2023.3.288364","DOIUrl":"https://doi.org/10.14739/2409-2932.2023.3.288364","url":null,"abstract":"Pain represents a primary symptom of numerous diseases and conditions, affecting millions of people worldwide. Effective analgesic medications can alleviate or eliminate pain, thereby enhancing patients’ quality of life and assisting them in resuming normal physical and social activities. However, several existing analgesics may carry unwanted side effects, such as ulcers, blood clotting issues, drowsiness, and more. The development of new analgesics is focused on creating drugs that are both effective and associated with fewer adverse effects. Considering the continuous rise in the number of patients dealing with neurological, oncological, and other conditions accompanied by chronic pain, there is a growing demand for innovative methods of treatment and pain management. The combination of two different heterocyclic fragments within one molecule makes it possible to use the possibilities of influencing such a molecule on various mechanisms of occurrence and development of various pathological conditions, including those accompanied by pain. Chemical modifications of pyrazole and 1,2,4-triazole structures, involving their incorporation into a single molecule, have the potential, as suggested by in silico predictions, to yield biologically active compounds with analgesic properties. The aim of this work was to determine the optimal conditions for the chemical transformation and properties of 4-amino-5-(3-methylpyrazol-5-yl)-1,2,4-triazole-3-thiol, 4-amino-5-(3-(3-fluorophenyl)pyrazol-5-yl)-1,2,4-triazole-3-thiol and their derivatives for the preparation of bioactive systems with analgesic activity. Materials and methods. The creation of a target series of compounds was implemented by consistently using well-known methods of organic synthesis. 4-Amino-5-(3-methylpyrazole-5-yl)-1,2,4-triazole-3-thiol and 4-amino-5-(3-(3-fluorophenyl)pyrazole-5-yl)-1,2,4-triazole-3-thiol were resynthesized as starting materials using acetone or 1-(3-fluorophenyl)ethane-1-one, diethyloxalate, and sodium methylate using step-by-step hydrazinolysis and carbon disulfide involvement in an alkaline medium. Further targeted functionalization involved the introduction of a 2,6-dichlorophenyl substitute, alkane acid residues, and esters based on them into the structure of the target compounds. The structure of all synthesized substances was determined by IR spectrophotometry, 1H NMR spectroscopy, and elemental analysis. The individuality of the compounds was confirmed by high-performance liquid chromatography-mass spectrometry. The analgesic properties were studied on two models: the “acetic acid-induced writhing test” and a formalin model of pain inflammation. Pharmacokinetic parameters were predictably calculated using the SwissADME online platform. Results. Based on the results of the synthetic part of the work, the structure of 4-amino-5-(3-methylpyrazole-5-yl)-1,2,4-triazole-3-thiol and 4-amino-5-(3-(3-fluorophenyl)pyrazole-5-yl)-1,2,4-triazole-3-thiol, as well as their d","PeriodicalId":10800,"journal":{"name":"Current issues in pharmacy and medicine: science and practice","volume":"300 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139290028","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}
引用次数: 0
Antioxidant, antimicrobial and antifungal activity of the obtained “Cachisept” tablets for resorption in the oral cavity for the treatment and prevention of dental caries 用于治疗和预防龋齿的 "Cachisept "口腔吸收片剂的抗氧化、抗菌和抗真菌活性
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.285425
O. Maslov, BD M. A. Komisarenko A, BD S. V. Ponomarenko A, BD V. Kolisnyk A, F. T. P. O. E, F. T. A. K. E, Yu. S. Kolisnyk, V. Moroz, О. Ю. Маслов, М. А. Комісаренко, С. В. Пономаренко, С. В. Колісник, Т. П. Осолодченко, Т. А. Костіна, Ю. С. Колісник, В. П. Мороз
Dental caries stands as a highly common chronic ailment affecting individuals globally, with susceptibility to this condition spanning their entire lifespan. Consequently, the search for novel medications aimed at treating and preventing dental caries holds significant importance in the field of pharmacy. The aim of the work was to study the antioxidant, antimicrobial, and antifungal activity of the obtained oral tablets “Сaсhisept” for resorption in the oral cavity for the treatment and prevention of dental caries. Materials and methods. The obtained tablets “Сaсhisept” with green tea leaf extract were the object of investigation. Antioxidant activity was established by the potentiometric method, and antimicrobial and antifungal activity was assessed by the agar well diffusion method. Results. The level of antioxidant activity for tablets “Сaсhisept” was 110.00 ± 2.20 mmol-eqv./mdry res, the obtained tablets had a high level of antioxidant activity according to Maslov’s conditional classification. Staphylococcus aureus (25.33 ± 0.50 mm), Baсillus subtilis (25.33 ± 0.50 mm) and Streptococcus mutans (25.33 ± 0.50 mm) were the most sensitive to the obtained “Сaсhisept” tablets, and the least – Proteus vulgaris (20.67 ± 0.50 mm), and it was observed strong growth inhibition in relation to the fungus Candida albicans (20.00 ± 0.50 mm). Conclusions. The presented study has found that “Сaсhisept” tablets have a high level of antioxidant activity, and also have a high antimicrobial and antifungal effect against all investigated Gram-positive, Gram-negative bacteria, and the Candida albicans fungus. Thus, “Сaсhisept” tablets can be recommended for the treatment and prevention of dental caries.
龋齿是影响全球个人的一种非常常见的慢性疾病,其易感性贯穿人的一生。因此,寻找治疗和预防龋齿的新型药物在药学领域具有重要意义。这项工作的目的是研究获得的口服片剂 "Сaсhisept "在治疗和预防龋齿方面的抗氧化、抗菌和抗真菌活性。材料和方法研究对象是含有绿茶叶提取物的 "Сaсhisept "药片。抗氧化活性通过电位计法确定,抗菌和抗真菌活性通过琼脂井扩散法评估。研究结果Сaсhisept "药片的抗氧化活性水平为 110.00 ± 2.20 mmol-eqv./mdryres,根据马斯洛夫的条件分类法,获得的药片具有较高的抗氧化活性。金黄色葡萄球菌(25.33 ± 0.50 mm)、枯草杆菌(25.33 ± 0.50 mm)和变异链球菌(25.33 ± 0.50 mm)对 "Сaсhisept "药片最敏感,而普通变形杆菌(20.67 ± 0.50 mm)对 "Сaсhisept "药片最不敏感。结论本研究发现,"Сaсhisept "药片具有很高的抗氧化活性,对所有研究的革兰氏阳性菌、革兰氏阴性菌和白色念珠菌都有很强的抗菌和抗真菌作用。因此,"Сaсhisept "片剂可推荐用于治疗和预防龋齿。
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引用次数: 0
In silico evaluation of the pharmacodynamic component of the interaction of S-alkyl derivatives of 5-methyl-4-(p-tolyl)-1,2,4-triazole-3-thiol with some biological targets 对 5-甲基-4-(对甲苯基)-1,2,4-三唑-3-硫醇的 S-烷基衍生物与某些生物靶标相互作用的药效学成分进行硅学评估
Pub Date : 2023-11-03 DOI: 10.14739/2409-2932.2023.3.287510
O. Panasenko, V. M. Odyntsova, A. S. Hotsulia
Derivatives of 1,2,4-triazole open wide opportunities for modern and progressive scientists in the development of innovative medicines. These compounds are known for their variability and structural flexibility, which allows scientists to experiment and create new molecules with unique properties. The use of 1,2,4-triazole derivatives in the creation of drugs is based on their ability to interact with biological systems and molecular targets. These compounds can be aimed at regulating physiological processes, reducing manifestations of pathological conditions or enhancing necessary biological reactions. Directed modification of the structure of 1,2,4-triazole derivatives allows to create biologically active compounds with improved properties. The aim of the work was to study in silico and to evaluate the possible interaction of a virtual series of S-alkyl derivatives of 5-methyl-4-(p-tolyl)-1,2,4-triazole-3-thiol with some enzyme systems. Materials and methods. A computer method (molecular docking) for predicting and evaluating the interaction between a ligand molecule and a target protein structure. Ligand preparation was performed using MarvinSketch 6.3.0, Hyper Chem 8, and AutoDockTools-1.5.6 programs. Enzyme preparation involved the use of Discovery Studio 4.0 and AutoDockTools-1.5.6 software packages. Direct molecular docking was performed using the Vina program. Results. A virtual series of S-alkyl derivatives of 5-methyl-4-(p-tolyl)-1,2,4-triazole-3-thiol with the potential possibility of creating a biologically active substance has been constructed. Using the Vina software tool, the nature and number of amino acid residues of the active centers of model enzymes, with which the proposed ligands coordinate and bind, were determined. According to the results of docking studies, the predicted affinity for lanosterol-14α-demethylase was determined. The effect on the receptor tyrosine kinase of anaplastic lymphoma is somewhat inferior in terms of qualitative and quantitative indicators. Conclusions. Using the method of molecular docking, it was established that S-alkyl derivatives of 5-methyl-4-(p-tolyl)-1,2,4-triazole-3-thiol have a fairly significant potential for the manifestation of antifungal activity, which justifies the further synthesis of these compounds and more in-depth study of fungistatic and fungicidal properties. Docking results for anaplastic lymphoma kinase show little promise in the development of anticancer agents.
1,2,4-三唑的衍生物为现代先进科学家开发创新药物提供了广阔的机遇。这些化合物以其可变性和结构灵活性而著称,这使得科学家们可以进行实验,创造出具有独特性质的新分子。1,2,4-三唑衍生物之所以能被用于制造药物,是因为它们能够与生物系统和分子靶点相互作用。这些化合物可用于调节生理过程、减轻病理症状或增强必要的生物反应。对 1,2,4-三唑衍生物的结构进行定向修饰,可以制造出具有更好特性的生物活性化合物。这项工作的目的是对 5-甲基-4-(对甲苯基)-1,2,4-三唑-3-硫醇的一系列 S-烷基虚拟衍生物与一些酶系统可能产生的相互作用进行硅学研究和评估。材料和方法采用计算机方法(分子对接)预测和评估配体分子与目标蛋白质结构之间的相互作用。配体制备使用 MarvinSketch 6.3.0、Hyper Chem 8 和 AutoDockTools-1.5.6 程序。酶的制备使用了 Discovery Studio 4.0 和 AutoDockTools-1.5.6 软件包。直接分子对接使用 Vina 程序进行。结果我们构建了一个 5-甲基-4-(对甲苯基)-1,2,4-三唑-3-硫醇的 S-烷基衍生物虚拟系列,该系列有可能产生一种生物活性物质。利用 Vina 软件工具,确定了模型酶活性中心氨基酸残基的性质和数量,拟议配体与之配位和结合。根据对接研究的结果,确定了与羊毛甾醇-14α-脱甲基酶的亲和力。从定性和定量指标来看,对无性淋巴瘤受体酪氨酸激酶的作用略逊一筹。结论。利用分子对接的方法,确定了 5-甲基-4-(对甲苯基)-1,2,4-三唑-3-硫醇的 S-烷基衍生物在抗真菌活性方面具有相当大的表现潜力,这为进一步合成这些化合物并更深入地研究其抑菌和杀菌特性提供了依据。针对无性淋巴瘤激酶的 Docking 结果表明,开发抗癌药物的前景并不乐观。
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引用次数: 0
期刊
Current issues in pharmacy and medicine: science and practice
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