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The impact of valproic acid and 2-propyl-4-pentenoic acid on antioxidant status measured by GSH/GSSG ratio and FRAP levels in acute and chronic exposure 丙戊酸和2-丙基-4-戊酸对急性和慢性暴露中GSH/GSSG比值和FRAP水平测定的抗氧化状态的影响
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-07-03 DOI: 10.32383/appdr/168836
Karina Sommerfeld-Klatta, Magdalena Łukasik-Głębocka, Sylwia Kobyłka, B. Zielińska-Psuja
Valproic acid (VPA) is a broad-spectrum anticonvulsant drug. Its mechanism of action includes enhancing GABAergic transmission, blocking voltage-gated sodium channels, and affecting dopaminergic and serotonergic transmission (1). The mechanism of VPA toxicity, including its effects on the liver, is not fully known. It is assumed that oxidative stress and/or reactive products of drug biotransformation are responsible for its hepatotoxicity (2). The aim of the study was to verify the hypothesis concerning the influence of valproic acid and its metabolite, 2-propyl-4-pentenoic acid (4-en VPA) on the antioxidant status of patients treated with (VPA-T) and poisoned with valproic acid (VPA-P). The VPA-P group was divided into patients with (VPA-Ptox) and without (VPA-Pnon) toxic symptoms observed during the hospitalization. Oxidative stress was assessed using markers, such as antioxidant potential (FRAP) and reduced and oxidised glutathione (GSH/GSSG) ratio were measured in the plasma of the study patients. The obtained results showed statistically significant differences between the concentrations of the drug and its active metabolite levels in the VPA-T and VPA-P groups. In the VPA-P group, the increase of the level of 4-en VPA in the plasma correlated with the increase of the concentration of the drug. The influence of VPA on the antioxidant balance in both groups of patients was demonstrated. The plasma antioxidant potential of FRAP decreased with increasing valproic acid concentrations in the VPA-Ptox group. The lowest concentrations of GSH/GSSG ratio were found in the VPA-Pnon group, without symptoms of intoxication during hospitalization.
丙戊酸(VPA)是一种广谱抗惊厥药物。其作用机制包括增强GABA能传递、阻断电压门控钠通道以及影响多巴胺能和5-羟色胺能传递(1)。VPA毒性的机制,包括其对肝脏的影响,尚不完全清楚。据推测,氧化应激和/或药物生物转化的反应产物是其肝毒性的原因(2)。本研究的目的是验证丙戊酸及其代谢产物2-丙基-4-戊烯酸(4-en-VPA)对接受(VPA-T)治疗和丙戊酸(VPA-P)中毒患者抗氧化状态影响的假设。VPA-P组被分为在住院期间观察到的有(VPA-Ptox)和没有(VPA-Pnon)毒性症状的患者。使用抗氧化电位(FRAP)等标志物评估氧化应激,并测量研究患者血浆中还原和氧化谷胱甘肽(GSH/GSSG)的比率。所获得的结果显示,在VPA-T和VPA-P组中,药物浓度及其活性代谢产物水平之间存在统计学上的显著差异。在VPA-P组中,血浆中4-en-VPA水平的增加与药物浓度的增加相关。VPA对两组患者抗氧化平衡的影响已得到证实。在VPA-Ptox组中,FRAP的血浆抗氧化潜力随着丙戊酸浓度的增加而降低。VPA-Pnon组GSH/GSSG比值最低,住院期间无中毒症状。
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引用次数: 0
Genistein - characterization of the molecule, similarity to estradiol and pharmacological potential 染料木素-分子特征、与雌二醇的相似性和药理潜力
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-29 DOI: 10.32383/appdr/161915
Kacper Kossakowski, A. Pawełczyk, L. Zaprutko
In recent years, the scientific world has become more interested in genistein. It has been the subject of extensive research for its potential in treating various diseases and as a functional food. The medical benefits of genistein are well documented in the literature. Several studies have been performed to better understand the mechanisms of its beneficiary effects on health and to improve its pharmacokinetic and pharmacodynamic parameters. It has been approved for relieving menopausal symptoms and has received attention for its use in the treatment of inflammatory and age-related disorders, cancer, metabolic illnesses, genetic disorders, and skin care. Genistein shows considerable similarity to endogenous estradiol. It is classified in the group known as phytoestrogens which exhibit properties corresponding to estrogen in the human body. The estrogenic activity resulting from the aforementioned similarity in the appearance of genistein and estradiol molecules makes it possible for genistein to act as both an estrogen agonist and antagonist, depending on the number of endogenous hormones present in the environment in which it is found and the type of tissue. The similarity of the chemical structure of genistein and estradiol and interactions occurring between estradiol and genistein and the amino acid binding site of the estrogen receptors were analyzed. Further controlled trials are needed to determine the efficacy and safety of genistein. Future research will focus on enhancing its bioavailability through structural modification and innovative delivery methods and conducting human trials to confirm its biological and pharmacological effects.
近年来,科学界对染料木素越来越感兴趣。由于其在治疗各种疾病和作为功能性食品方面的潜力,它一直是广泛研究的主题。染料木黄酮的医学益处在文献中有很好的记载。已经进行了几项研究,以更好地了解其对健康的受益作用机制,并改善其药代动力学和药效学参数。它已被批准用于缓解更年期症状,并因其用于治疗炎症和年龄相关疾病、癌症、代谢疾病、遗传疾病和皮肤护理而受到关注。染料木素与内源性雌二醇表现出相当大的相似性。它被归类为植物雌激素,表现出与人体雌激素相对应的特性。由染料木素和雌二醇分子外观的上述相似性产生的雌激素活性使染料木素有可能同时作为雌激素激动剂和拮抗剂,这取决于发现染料木素的环境中存在的内源性激素的数量和组织类型。分析了染料木素和雌二醇化学结构的相似性,雌二醇和染料木素之间的相互作用以及雌激素受体的氨基酸结合位点。需要进一步的对照试验来确定染料木素的疗效和安全性。未来的研究将侧重于通过结构修饰和创新的给药方法提高其生物利用度,并进行人体试验以确认其生物和药理作用。
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引用次数: 0
Application of response surface methodology in the development of parenteral emulsion using ultrasonic emulsification 响应面法在超声乳化胃肠外乳液研制中的应用
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-29 DOI: 10.32383/appdr/168239
A. Gostyńska, J. Jańczak
Abstract: Intravenous lipid emulsion is a critical component of parenteral nutrition. Long-term administration of such therapy lead to liver dysfunction. As the cause of liver failure can be the size of lipid emulsion droplets, their reduction can positively affect the clinical condition of patients. This study aimed to develop and optimize the preparation process of intravenous lipid emulsions with reduced droplet size compared to commercially available formulations. The response surface methodology was applied to optimize the ultrasonic emulsification. The reduction of lipid droplet size was achieved by the use of a combination of 1.2% (w/w) soy phospholipids and various concentrations of Tween 80 (2, 3, and 4% (w/w)). The other variables were sonication amplitude and time of sonication. During the optimization process, fifteen soybeans oil-based intravenous lipid emulsions were developed. All formulations were characterized by the physicochemical properties appropriate for intravenous administration, i.e., MDD ranging from 119.1 ± 0.6 nm to 177.1 ± 2.1 nm, PdI below 0,219 ± 0,009. The pH and osmolarity ranged from 6.23 ± 0.01 to 6.58 ± 0 and from 328 ± 3 to 568 ± 8 mOsm/kg, respectively. The Box Behnken methodology allowed for optimizing the preparation of intravenous lipid emulsion using ultrasonic emulsification.
摘要:静脉脂质乳剂是肠外营养的重要组成部分。长期服用这种疗法会导致肝功能障碍。由于肝衰竭的原因可能是脂质乳液液滴的大小,其减少会对患者的临床状况产生积极影响。本研究旨在开发和优化静脉注射脂质乳液的制备工艺,与市售制剂相比,该乳液的液滴尺寸更小。应用响应面法对超声乳化过程进行了优化。通过使用1.2%(w/w)的大豆磷脂和不同浓度的吐温80(2%、3%和4%(w/w))的组合来实现脂滴尺寸的减小。其他变量是超声振幅和超声时间。在优化过程中,开发了15种豆油基静脉脂质乳剂。所有制剂都具有适合静脉给药的物理化学性质,即MDD范围为119.1±0.6 nm至177.1±2.1 nm,PdI低于0219±0009。pH和渗透压分别为6.23±0.01至6.58±0和328±3至568±8mOsm/kg。Box-Behnken方法允许使用超声乳化优化静脉脂质乳液的制备。
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引用次数: 0
The application of cannabidiol in the treatment of glioblastoma 大麻二酚在胶质母细胞瘤治疗中的应用
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-29 DOI: 10.32383/appdr/163414
A. Rybarczyk, A. Majchrzak-Celińska, V. Krajka-Kuźniak
Glioblastoma multiforme (GBM), a high-grade astrocytoma, is an incurable brain tumor associated with genetic heterogeneity and dysregulated signaling pathways. As alternations of the endocannabinoid system have been demonstrated in GBM cells, the substances affecting its key elements may potentially inhibit tumor progression. Preclinical models indicate that CBD inhibits GBM tumor growth by inhibiting cellular proliferation, migration, and invasion but also promotes autophagy and apoptosis of tumor cells. Moreover, clinical trials indicate the safety and positive results regarding the survival of GBM patients upon cannabinoids treatment. Nevertheless, more human clinical trials with large sample sizes are urgently needed to implement cannabinoids, including CBD, into standard GBM treatment.
多形性胶质母细胞瘤(GBM)是一种高度星形细胞瘤,是一种无法治愈的脑肿瘤,与遗传异质性和信号通路失调有关。内源性大麻素系统的改变已经在GBM细胞中得到证实,影响其关键元素的物质可能潜在地抑制肿瘤进展。临床前模型表明,CBD通过抑制细胞增殖、迁移和侵袭来抑制GBM肿瘤的生长,同时也促进肿瘤细胞的自噬和凋亡。此外,临床试验表明大麻素治疗对GBM患者的生存具有安全性和积极的结果。然而,迫切需要更多的大样本量的人体临床试验来实施大麻素,包括CBD,用于标准的GBM治疗。
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引用次数: 1
Synthesis of curcumin derivatives containing non-steroidal anti-inflammatory drugs 含非甾体抗炎药的姜黄素衍生物的合成
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-29 DOI: 10.32383/appdr/161972
Katarzyna Sowa-Kasprzak, Dorota Olender, J. Kujawski, L. Zaprutko, A. Pawełczyk
Synthesis and biological evaluation of hybrid molecules combining naturally occurring antioxidant active structures with anti-inflammatory agents has been a strong trend in medicinal chemistry. This study focuses on modulating the structure of curcumin derivatives or their analogues with the use of non-steroidal anti-inflammatory drugs (NSAIDs). The combinations of curcumin, its keto-blocked derivatives and monocarbonyl analogues with selected non-steroidal anti-inflammatory drugs (ibuprofen, naproxen) were obtained and characterized. The pyrazole, isoxazole, benzylidene derivatives as well as curcumin monocarbonyl analogues were used as substrates in the reactions with selected NSAIDs. As a result of the esterification of curcumin-type diphenol, the corresponding mono- and diester-type derivatives were also obtained and characterized. Moreover, the estimated values of binding affinities and the binding sites of docked derivatives were deduced from modeling studies were very favorable. Results obtained show the binding potential of curcumin and its analogs to the host-targeted proteins nucleocapsid phosphoprotein (PDB ID: 6VYO) structure. Additionally, with the use of selected methods of computational chemistry (Molinspiration Cheminformatics and Osiris Property Explorer) the molecular parameters of the relevant molecules were calculated.
天然抗氧化活性结构与抗炎药结合的杂化分子的合成和生物学评价已成为药物化学研究的一个重要方向。本研究的重点是使用非甾体抗炎药(NSAIDs)调节姜黄素衍生物或其类似物的结构。研究了姜黄素及其酮阻断衍生物和单羰基类似物与非甾体抗炎药(布洛芬、萘普生)的联合作用。以吡唑、异恶唑、苄基衍生物和姜黄素单羰基类似物为底物,与选定的非甾体抗炎药进行反应。通过姜黄素型双酚的酯化反应,得到了相应的单酯型和双酯型衍生物,并对其进行了表征。此外,通过模型研究推导出的对接衍生物的结合亲和力和结合位点的估价值是非常有利的。结果显示姜黄素及其类似物与宿主靶蛋白核衣壳磷酸化蛋白(PDB ID: 6VYO)结构的结合潜力。此外,利用计算化学方法(Molinspiration Cheminformatics和Osiris Property Explorer)计算了相关分子的分子参数。
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引用次数: 1
Determination of pKa values of fluphenazine analogs by reversed-phase high-performance liquid chromatography 反相高效液相色谱法测定氟奋乃嗪类似物的pKa值
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-29 DOI: 10.32383/appdr/165805
Sobczak-Kupiec Agnieszka, Beata Kaźmierska, P. Świątek, Izabela Muszalska-Kolos
Phenothiazine and its derivatives exhibit many properties. Hence they are the starting structuresfor many new potential drugs, biologically active compounds, dyes, etc. In this paper, weinvestigated a series of five fluphenazine analogs synthesized exhibiting inhibition of multidrugresistance (MDR) in tumor cells. During the drug discovery process, the determination ofphysicochemical properties of new compounds, such as dissociation constant values (pKa), isessential because it directly affects their pharmacokinetic profile. Thus, this study aimed todetermine the pKa values of fluphenazine and its derivatives from the mobile phase pHdependence of the retention factor with the reverse phase liquid chromatographic method.Binary mixtures of phosphate buffer (pH 2.3-11.5) and acetonitrile (40-55%) in differentpercentages and the Gemini NX C18 column as the stationary phase were used in the tests. ThepKa' values of fluphenazine derivatives at experimental concentrations of organic solvent weredetermined based on the obtained sigmoidal k curves as a function of pH. Then these valueswere extrapolated to 0% acetonitrile to obtain the actual pKa values. Moreover, a comparativeevaluation of chromatographically obtained and computationally calculated pKa parameterswas carried out.
吩噻嗪及其衍生物具有许多性质。因此,它们是许多潜在新药、生物活性化合物、染料等的起始结构。本文研究了一系列合成的五种对肿瘤细胞多药耐药性(MDR)具有抑制作用的氟吩嗪类似物。在药物发现过程中,测定新化合物的物理化学性质,如离解常数值(pKa),是至关重要的,因为它直接影响它们的药代动力学特征。因此,本研究旨在用反相液相色谱法从保留因子的流动相pH依赖性中确定氟奋乃嗪及其衍生物的pKa值。试验中使用不同百分比的磷酸盐缓冲液(pH 2.3-11.5)和乙腈(40-55%)的二元混合物,并使用Gemini NX C18柱作为固定相。根据所获得的作为pH函数的S形k曲线,测定了氟吩嗪衍生物在有机溶剂实验浓度下的pKa’值。然后将这些值外推到0%乙腈中,以获得实际的pKa值。此外,还对色谱法获得的pKa参数和计算得到的参数进行了比较评价。
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引用次数: 0
In search of new trends 寻找新的趋势
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-29 DOI: 10.32383/appdr/168232
M. Stawny
This issue presents a collection of selected papers from the International Conference NEW TRENDS in Polish and global pharmacy: Science, business, and modern education, which took place on September 29-30, 2022, Poznań, Poland.The conference aimed to develop an effective communication platform between science and business. Prominent specialists in science, education, and business who deal with the issues of developing bridges between these three sectors participated in the event. Scientific achievements, the latest research results, and the potential of medical universities as an offer for the pharmaceutical industry were presented.
本期精选了2022年9月29日至30日在波兰波兹南举行的波兰和全球药学新趋势:科学、商业和现代教育国际会议的论文集。会议旨在建立一个科学与商业之间有效的沟通平台。处理在这三个部门之间建立桥梁问题的科学、教育和商业领域的知名专家参加了此次活动。介绍了科学成果、最新研究成果以及医科大学为制药行业提供服务的潜力。
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引用次数: 0
Kinetic studies of fluorocurcumin derivatives with anticancer activity 具有抗癌活性的氟姜黄素衍生物动力学研究
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-29 DOI: 10.32383/appdr/163486
Joanna Kuźmińska, A. Sobczak, Izabela Muszalska-Kolos, A. Jelińska, Weronika Jankowska, T. Gośliński
Two novel fluorocurcumin adducts with a difluoroboryl group exhibited activity in vitro against two bladder cancer cell lines, namely 5637 and SCaBER. The stability was evaluated under physiologically relevant conditions to mimic both the digestive tract and the bladder environment. Therefore, experiments were performed in hydrochloric acid at pH 1.2, and in buffer solutions with pH from 4.5 to 6.8 at 37°C. A validated HPLC method, allowing the monitoring of changes in substrates and products concentrations over time, was applied. Notably, the main decomposition product was the fluorocurcumin derivative without the difluoroboryl group. The decomposition of the fluorocurcumin adducts to the major products undergoes the pseudo-first-order kinetics reaction.
两种新型的含二氟硼基的氟姜黄素加合物在体外对两种膀胱癌细胞株5637和scer有活性。在模拟消化道和膀胱环境的生理相关条件下评估其稳定性。因此,实验分别在pH为1.2的盐酸和pH为4.5 - 6.8的缓冲溶液中进行,温度为37℃。一种经过验证的高效液相色谱方法,允许监测底物和产物浓度随时间的变化。值得注意的是,主要的分解产物是不含二氟硼基的氟姜黄素衍生物。氟姜黄素加合物分解为主要产物的过程为准一级动力学反应。
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引用次数: 0
The role of pharmaceutical analysis in ensuring the safety of drug radiation sterilization 药物分析在确保药物辐射灭菌安全中的作用
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-29 DOI: 10.32383/appdr/163633
M. Ogrodowczyk, A. Kaczmarek, A. Gostyńska, A. Jelińska
Radiation sterilization is a widely used method for ensuring the sterility of medical and pharmaceutical products. The process involves exposing the products to ionizing radiation, which destroys microorganisms such as bacteria, viruses, and fungi, rendering the products sterile. The most commonly used ionizing radiation sterilization methods are highly penetrating with low dose rate gamma-irradiation from isotopic sources and less penetrating but with high dose rate e-beam from accelerators. This review provides an overview of the principles and applications of radiation sterilization, including the types of radiation sources used, the differences between them that may affect the efficacy of the process, and the regulatory requirements for radiation sterilization of active pharmaceutical ingredients and drug dosage forms. This review focuses on the analytical methods used to evaluate the effect of irradiation on drug substances. Finally, it discusses studies on radiation sterilization of various groups of drugs, including anthracyclines, β-lactam antibiotics, chloramphenicol and its derivatives, sulphonamides, antifungal drugs, β-blockers, nonsteroidal anti-inflammatory drugs, steroids, and others, and drug dosage forms.
辐射灭菌是一种广泛使用的确保医疗和药品无菌的方法。该过程包括将产品暴露在电离辐射下,电离辐射会破坏细菌、病毒和真菌等微生物,使产品无菌。最常用的电离辐射灭菌方法是利用同位素源的低剂量率伽马辐射进行高穿透性灭菌,以及利用加速器的高剂量率电子束进行低穿透性灭菌。本综述概述了辐射灭菌的原理和应用,包括使用的辐射源类型、可能影响工艺疗效的辐射源之间的差异,以及活性药物成分和药物剂型辐射灭菌的监管要求。本文综述了用于评价辐照对药物影响的分析方法。最后,讨论了蒽环类、β-内酰胺类抗生素、氯霉素及其衍生物、磺酰胺类、抗真菌药物、β-阻断剂、非甾体抗炎药、类固醇等药物的辐射杀菌研究,以及药物剂型。
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引用次数: 1
Preliminary assessment of influence of calcium alginate beads on the dissolution of meloxicam 藻酸钙微珠对美洛昔康溶出度影响的初步评价
IF 0.4 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-06-29 DOI: 10.32383/appdr/162533
Barbara Jadach, Weronika Świetlik, Ł. Majchrzycki
The purpose of the study was to evaluate the preparation of alginate-based microparticles with meloxicam (MLX). A poorly soluble substance classified to BCS class II, it was chosen as a model substance. The ionotropic gelation was the process used for the formation of microparticles. The impact of the carrier on the dissolution of MLX from this formulation was also investigated.Study was realized in few steps: preparation of polymer particles containing suspended MLX in their structure; drying them in various conditions (room temperature, freeze drying); morphology characterization and then assessment of impact of polymer on dissolution of the model substance. Also, DDSolver software was used for checking the similarity of release profiles. Validated UV-Vis spectrophotometric method was used for MLX determination on different steps of work. As it showed, calcium alginate particles were successfully prepared with ionotropic gelation. The drying method of prepared particles has a substantial impact on the release profiles of meloxicam, and these formulations significantly improve the MLX release from this form of the delivery system.
本研究旨在评价美洛昔康(MLX)制备海藻酸盐基微粒的工艺。它是一种难溶性物质,属于BCS II类,被选为模型物质。离子致凝胶化是用于形成微粒的过程。还研究了载体对MLX从该制剂中溶解的影响。研究分几个步骤实现:制备结构中含有悬浮MLX的聚合物颗粒;在各种条件下干燥(室温、冷冻干燥);形态表征,然后评估聚合物对模型物质溶解的影响。此外,DDSolver软件用于检查发布配置文件的相似性。经验证的紫外-可见分光光度法用于不同工作步骤的MLX测定。结果表明,采用离子致凝胶法成功制备了海藻酸钙颗粒。制备颗粒的干燥方法对美洛昔康的释放特性有很大影响,这些制剂显著改善了MLX从这种形式的递送系统中的释放。
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引用次数: 0
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Acta poloniae pharmaceutica
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