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DEVELOPMENT OF A FAST LIQUID CHROMATOGRAPHY METHOD WITH A CHEMOMETRIC APPROACH BASED ON BOX-BEHNKEN DESIGN FOR THE DETERMINATION OF ANTIDEPRESSANTS IN PHARMACEUTICAL FORMULATIONS 基于方框-贝肯设计的化学计量学方法开发快速液相色谱法,用于测定药物制剂中的抗抑郁药
Pub Date : 2024-04-01 DOI: 10.33483/jfpau.1425340
Sercan Yıldırım, Tuğçe Özyiğit
Objective: The objective of this work was to develop a liquid chromatographic method for the quantification of antidepressants, namely duloxetine (DXN), fluoxetine (FXN), citalopram (CIT), paroxetine (PXN), and sertraline (SRN), by a chemometric approach based on Box-Behnken design.Material and Method: After initial experiments to determine significant parameters, a Box-Behnken design consisting of 17 experiment sets was carried out. All separations were conducted using an Agilent Poroshell 120 EC-C18 analytical column (75 mm × 4.6 mm × 2.7 µm). Result and Discussion: The optimum levels of pH, acetonitrile ratio, and flow rate were determined with the desirability function as 2.7, 38%, and 1.1 ml/min, respectively. The differences (<8%) between predicted optimum responses and experimentally obtained results proved the model's suitability. Limits of detection and limits of quantification values were in the ranges of 0.17-0.29 µg/ml and 0.53-0.89 µg/ml, respectively. The feasibility of the technique was proven by analyzing PXN and DXN formulations.
研究目的本研究的目的是通过基于方框-贝肯设计的化学计量学方法,建立一种液相色谱法,用于定量分析抗抑郁药物,即度洛西汀(DXN)、氟西汀(FXN)、西酞普兰(CIT)、帕罗西汀(PXN)和舍曲林(SRN):经过初步实验确定重要参数后,进行了由 17 组实验组成的盒-贝肯设计。所有分离均使用 Agilent Poroshell 120 EC-C18 分析柱(75 mm × 4.6 mm × 2.7 µm)。结果与讨论用可取函数确定的最佳 pH 值、乙腈比例和流速分别为 2.7、38% 和 1.1 ml/min。预测的最佳反应与实验结果之间的差异(<8%)证明了该模型的适用性。检测限和定量限分别为 0.17-0.29 µg/ml 和 0.53-0.89 µg/ml。通过分析 PXN 和 DXN 制剂,证明了该技术的可行性。
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引用次数: 0
LIQUID AND SOLID SELF-EMULSIFYING DRUG DELIVERY SYSTEMS (SEDDS) CONTAINING VALSARTAN: STABILITY ASSESSMENT AND PERMEABILITY STUDIES 含有缬沙坦的液体和固体自乳化给药系统(SEDDS):稳定性评估和渗透性研究
Pub Date : 2024-03-28 DOI: 10.33483/jfpau.1385707
Gülbeyaz Yıldız Türkyılmaz, Mine Diril, Eda Gülmezoğlu, Y. Karasulu
Objective: Valsartan (VST) is a Biopharmaceutical classification system (BSC) class II active ingredient with a bioavailability of approximately 25% and is utilized to treat high blood pressure (hypertension). This study aimed was to showcase the stability and increase the permeability of VST by developing self-emulsifying drug delivery systems (SEDDS) and solidified SEDDS (S-SEDDS) formulations.Material and Method: The ratios of the components were determined by the pseudo-ternary phase diagram, and the characterization studies were conducted in the previous study. Stability was performed in long-term (25±2˚C, 60±5% relative humidity) and accelerated (40±2˚C, 75±5% relative humidity) conditions. The intestinal permeability of SEDDS formulations was evaluated by Caco-2 cells.Result and Discussion: Formulations for 12 month, droplet sizes were found to be 67.52 ± 5.26 nm and 176.93 ± 17.34 nm for SEDDS of VST (VST-SEDDS) and S-SEDDS of VST (VST-S-SEDDS), respectively. During this period, polydispersity indexes were: VST-SEDDS, 0.56±0.1; VST-S-SEDDS, 0.58±0.05. Both formulations increased VST permeability across Caco-2 cells: VST-SEDDS by 2.32x (powder) and 2.18x (commercial); VST-S-SEDDS by 1.38x (powder) and 1.30x (commercial). The formulation components did not have cytotoxic effects. These results demonstrated that newly developed VST-SEDDS and VST-S-SEDDS formulations with high permeability may be a desirable approach for antihypertensive therapy.
目的:缬沙坦(VST)是一种生物制药分类系统(BSC)二级活性成分,生物利用度约为 25%,用于治疗高血压。本研究旨在通过开发自乳化给药系统(SEDDS)和固化 SEDDS(S-SEDDS)制剂,展示 VST 的稳定性并提高其渗透性:材料: 根据假三元相图确定了各组分的比例,并在之前的研究中进行了表征研究。在长期(25±2˚C,相对湿度 60±5%)和加速(40±2˚C,相对湿度 75±5%)条件下进行了稳定性测试。Caco-2 细胞对 SEDDS 配方的肠道渗透性进行了评估:制剂使用 12 个月后,发现 VST 的 SEDDS(VST-SEDDS)和 VST 的 S-SEDDS(VST-SEDDS)的液滴尺寸分别为 67.52 ± 5.26 nm 和 176.93 ± 17.34 nm。在此期间,多分散指数为VST-SEDDS,0.56±0.1;VST-S-SEDDS,0.58±0.05。两种制剂都增加了 VST 在 Caco-2 细胞中的渗透性:VST-SEDDS 增加了 2.32 倍(粉末)和 2.18 倍(商品);VST-S-SEDDS 增加了 1.38 倍(粉末)和 1.30 倍(商品)。制剂成分没有细胞毒性作用。这些结果表明,新开发的高渗透性 VST-SEDDS 和 VST-S-SEDDS 制剂可能是一种理想的降压治疗方法。
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引用次数: 0
IN SILICO APPROACHES ON PHENYLALANINE HYDROXYLASE INHIBITOR-RELATED COMPOUNDS USED IN PARKINSON’S DISEASE TREATMENT 用于帕金森病治疗的苯丙氨酸羟化酶抑制剂相关化合物的硅学方法
Pub Date : 2024-03-26 DOI: 10.33483/jfpau.1380350
Hatice Akkaya, E. Sümer
Objective: In Parkinson’s disease, Levodopa with Carbidopa addresses dopamine deficiency. Phenylalanine hydroxylase catalyzes phenylalanine to tyrosine conversion crucial for dopamine synthesis. Inhibiting phenylalanine hydroxylase may enhance Carbidopa's effects, preventing peripheral dopamine synthesis. The study used virtual scanning, molecular docking, and dynamics simulation to explore phenylalanine hydroxylase interactions with Carbidopa and similar ligands. ADME/T assessments and drug similarity tests were conducted to evaluate therapeutic potential in biological systems.Material and Method: A molecular docking study was performed on the structures obtained from the PubChem database and human PAH (PDB ID: 6PAH) using Autodock Vina within Chimera 1.16. Furthermore, the ligands underwent ADME/T assays, which are crucial aspects in drug development.Result and Discussion: The study suggests that 2-(2-Aminohydrazinyl)-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid shows promise as a phenylalanine hydroxylase inhibitor for Parkinson's disease treatment, but further research is needed to assess its safety, efficacy, and specificity, particularly in extracerebral regions, while also exploring its potential to improve the effectiveness of Levadopa/Carbidopa combination therapy.
目的:对于帕金森病患者,左旋多巴和卡比多巴可解决多巴胺缺乏问题。苯丙氨酸羟化酶催化苯丙氨酸向酪氨酸的转化,对多巴胺的合成至关重要。抑制苯丙氨酸羟化酶可能会增强卡比多巴的作用,阻止外周多巴胺的合成。该研究利用虚拟扫描、分子对接和动力学模拟来探索苯丙氨酸羟化酶与卡比多巴和类似配体的相互作用。研究还进行了 ADME/T 评估和药物相似性测试,以评估其在生物系统中的治疗潜力:使用 Chimera 1.16 中的 Autodock Vina 对从 PubChem 数据库和人类 PAH(PDB ID:6PAH)中获得的结构进行了分子对接研究。此外,还对配体进行了 ADME/T 试验,这在药物开发过程中至关重要:研究表明,2-(2-氨基肼基)-3-(3,4-二羟基苯基)-2-甲基丙酸有望作为苯丙氨酸羟化酶抑制剂用于帕金森病的治疗,但还需要进一步的研究来评估其安全性、有效性和特异性,尤其是在脑外区域的特异性,同时还要探索其改善左旋多巴/卡比多巴联合疗法有效性的潜力。
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引用次数: 0
KİMYASAL SİLAHLARA VE BİYOTERÖRE KARŞI TEDAVİDE KULLANILAN UYGULAMALAR 在处理化学武器和生物恐怖主义方面的应用
Pub Date : 2024-02-27 DOI: 10.33483/jfpau.1363452
Sibel İLBASMIŞ TAMER, İlkay ERDOĞAN ORHAN
Objective: In the present study, the chemical and physical properties of various chemical warfare agents, general information about medical protection methods, current analysis methods equipment, decontamination techniques and pharmaceutical formulations used when exposed to chemical agents will be discussed.Result and Discussion: Among weapons of mass destruction, chemical warfare agents are one of the most brutal dangers posed to humanity compared to biological and nuclear weapons. These war agents can be produced easily, cheaply and can cause mass casualties in small amounts with chemicals that are easily obtained in our daily lives, even by small terrorist groups. Chemical warfare agents can enter the body through various routes; and symptoms may vary accordingly. When inhaled, gases, vapors and aerosols can be absorbed through any part of the respiratory tract, from the mucosa of the nose and mouth to the alveoli of the lungs. The eye may able to absorb these agents directly. Liquid droplets and solid particles can be absorbed from the surface of the skin and mucous membranes. Toxic compounds that have a characteristic effect on the skin can demonstrate their effects when they accumulate on the skin as solid or liquid particles. The vapors of some volatile substances can penetrate intact skin and subsequently cause poisoning. Wounds or abrasions are more permeable than intact skin. Chemical warfare agents can contaminate food and beverages and absorbed into the gastrointestinal tract. While chemical warfare agents penetrate through various transmucosal routes, they can cause irritation or damage to the surfaces. In addition, toxic substances can pollute groundwater, leaking into the environment by soil and air and cause long-term harmful effects on living organisms.
研究目的:在本研究中,将讨论各种化学战剂的化学和物理特性、有关医疗保护方法的一般信息、当前的分析方法设备、净化技术以及接触化学战剂时使用的药物配方:在大规模毁灭性武器中,与生物武器和核武器相比,化学战剂是对人类构成的最残酷的危险之一。这些战剂可以很容易地生产出来,价格低廉,而且可以用我们日常生活中很容易获得的化学物质造成少量的大规模伤亡,即使是小型恐怖组织也可以做到这一点。化学战剂可通过各种途径进入人体,症状也会相应不同。吸入时,气体、蒸汽和气溶胶可通过呼吸道的任何部位被吸收,从口鼻粘膜到肺泡。眼睛可以直接吸收这些制剂。液滴和固体颗粒可从皮肤和粘膜表面吸收。对皮肤有特殊作用的有毒化合物以固体或液体颗粒的形式在皮肤上积聚时,就会显示出它们的作用。某些挥发性物质的蒸气可以穿透完整的皮肤,继而引起中毒。伤口或擦伤比完整皮肤的渗透性更强。化学战剂可污染食物和饮料,并被胃肠道吸收。虽然化学战剂可通过各种经黏膜途径渗透,但它们会对人体表面造成刺激或损害。此外,有毒物质会污染地下水,通过土壤和空气泄漏到环境中,对生物体造成长期有害影响。
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引用次数: 0
NANOPARTICLES FOR DUAL IMAGING: PET AND FLUORESCENCE IMAGING 用于双重成像的纳米粒子:宠物和荧光成像
Pub Date : 2024-02-22 DOI: 10.33483/jfpau.1323924
E. T. Sarcan
Objective: Molecular imaging methods are gaining popularity in clinical and preclinical fields. There are many different imaging methods such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT) and Near-infrared fluorescence (NIRF), and each has different advantages and disadvantages. Multimodal imaging methods, a combination of two or more molecular imaging modalities, have been developed to overcome the disadvantages of these molecular imaging methods. However, these imaging methods are conjugated with different vectors to improve the multimodal imaging methods used. In this field, drug delivery systems, peptides, proteins, antibodies and aptamers have been widely used for conjugation of multimodal imaging modalities to overcome some of the disadvantages that come from imaging modalities. In this review, PET and NIRF combination imaging modalities were explained and more specifically PET and NIRF nanoparticle dual imaging modalities with their pros and cons were investigated.Result and Discussion: Dual imaging modalities overcome to limitations of single imaging modalities and provide a better understanding of biological, anatomical, and physiological processes. Multimodal imaging modalities offer higher sensitivity, resolution, and specificity withlower cost and toxicity although have several disadvantages.
目的:分子成像方法在临床和临床前领域越来越受欢迎。有许多不同的成像方法,如计算机断层扫描(CT)、磁共振成像(MRI)、正电子发射断层扫描(PET)、单光子发射计算机断层扫描(SPECT)和近红外荧光(NIRF),每种方法都有不同的优缺点。为了克服这些分子成像方法的缺点,人们开发了多模态成像方法,即两种或两种以上分子成像模式的组合。不过,这些成像方法都与不同的载体共轭,以改进所使用的多模态成像方法。在这一领域,药物输送系统、肽、蛋白质、抗体和适配体已被广泛用于多模态成像方法的共轭,以克服成像方法的一些缺点。本综述对正电子发射计算机断层显像和近红外荧光联合成像模式进行了解释,并更具体地研究了正电子发射计算机断层显像和近红外荧光纳米粒子双重成像模式的利弊:双重成像模式克服了单一成像模式的局限性,能更好地了解生物、解剖和生理过程。多模态成像模式具有更高的灵敏度、分辨率和特异性,成本和毒性较低,但也有一些缺点。
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引用次数: 0
ENFLAMATUAR BAĞIRSAK HASTALIĞI VE TIBBİ BİTKİLER: GÜNCEL BİR GÖZDEN GEÇİRME 炎症性肠病与药用植物:最新综述
Pub Date : 2024-02-18 DOI: 10.33483/jfpau.1393243
Ece Bayir, Gözde ELGİN CEBE
Amaç: Enflamatuar bağırsak hastalığı (EBH), ülserasyon, kanama, sıvı ve elektrolit kaybı ile karakterize, atak ve remisyon dönemlerinden oluşan gastrointestinal sistemin (GİS) kronik enflamasyonudur. Ülseratif kolit ve Chron, etiyolojisi ve patogenezi tam olarak belli olmayan EBH’nin majör klinik formlarıdır. Son yıllarda ülkemizde ve dünyada insidansı ve prevalansı gittikçe artan EBH, bireylerin yaşam kalitesini olumsuz etkilemektedir. Bu durum hastalığın tedavisini daha da önemli hale getirmektedir. Fakat bu tedavi yöntemleri hastalığın remisyon süresinin uzatılması ve progresyonunun önlenmesi için yetersiz kalabilmektedir. Bu nedenle hastalar esas tedavilerine ek olarak farklı tamamlayıcı tedavi arayışlarına yönelmektedir. Bu yöntemler arasında hastaların en sık başvurduğu tamamlayıcı tedavi, bitkisel ürünlerdir. Sonuç ve Tartışma: Bitkisel ürünlerin kullanımı, hastalık üzerinde olumlu etkiler yapabildiği gibi olumsuz etkilere de yol açabilmektedir. Bu nedenle belli standartlara sahip ürünlerin uygun hastalıkta, uygun formda, uygun dozda ve hekim/eczacı kontrolünde kullanılması gerekmektedir. Literatürdeki çalışmalar değerlendirildiğinde; enflamatuar bağırsak hastalıklarında kullanılan tıbbi bitkilerin fazlalığına rağmen birçoğunun potansiyel etki mekanizmasının ve olumlu/olumsuz etkilerinin tam olarak ortaya konmadığı görülmektedir. Bu bitkilerin yanlış ve bilinçsizce kullanımı hastalığın seyrinin kötüleşmesine yol açabileceğinden enflamatuar bağırsak hastalıklarında kullanılan tıbbi bitkilerle ilgili daha fazla araştırmaya ihtiyaç duyulmaktadır.
目的:炎症性肠病(IBD)是以溃疡、出血、体液和电解质流失为特征的胃肠道慢性炎症,有发作期和缓解期。溃疡性结肠炎和慢性结肠炎是 IBD 的主要临床形式,其病因和发病机制尚不清楚。近年来,IBD 在我国乃至全世界的发病率和患病率都在不断上升,对患者的生活质量造成了负面影响。这种情况使得疾病的治疗变得更加重要。然而,这些治疗方法可能不足以延长缓解期和防止病情恶化。因此,除了主要的治疗方法外,患者还会寻求不同的辅助疗法。在这些方法中,草药产品是最常用的辅助疗法。结论与讨论:使用草药产品可能会对疾病产生积极影响,也可能会产生消极影响。因此,应在医生/药剂师的指导下,以适当的形式、适当的剂量、适当的疾病使用符合一定标准的产品。对文献中的研究进行评估后发现,尽管用于炎症性肠病的药用植物数量很多,但其中许多植物的潜在作用机制和积极/消极作用尚未完全揭示。由于不正确和无意识地使用这些植物可能会导致疾病恶化,因此需要对用于炎症性肠病的药用植物进行更多的研究。
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引用次数: 0
İNSAN PAPİLLOMA VİRÜSÜ (HPV) TEDAVİSİNDE YENİ YAKLAŞIMLAR: AKTİF HEKSOZ İLİŞKİLİ BİLEŞİK (AHCC®) 治疗人类乳头瘤病毒(HPV)的新方法:活性己糖相关化合物 (AHCC®)
Pub Date : 2024-02-18 DOI: 10.33483/jfpau.1364203
Zehra Keçeci̇, Cansu Bölükbaş, Hazal Eken
Amaç: İnsan papilloma virüsü (HPV) alt tiplerine bağlı olarak cilt ve mukoza zarlarında siğil ve kanser oluşumuna sebep olabilen cinsel yolla bulaşan en yaygın viral enfeksiyon olması sebebi ile ciddi bir halk sağlığı problemi oluşturmaktadır. Günümüzde HPV tedavisinde hastalığın eradikasyonunu sağlamayan, sadece dışa doğru büyüyen siğillerin uzaklaştırılmasını ve semptomların iyileştirilmesini amaçlayan seçenekler mevcuttur. Bu tedavilerin dışında immün sistemi destekleyici çeşitli doğal ürünlerin kullanımının da HPV tedavisinde faydalı olabileceği gösterilmiştir. Mantar ekstraktlarının bağışıklık sistemi üzerindeki kesin etkileri tam olarak aydınlatılamamış olsa da uzun yıllardan beri dünyanın farklı bölgelerinde çeşitli sağlık sorunları için kullanılmaktadır. Bu derlemede bir mantar ekstratı olan AHCC®’nin HPV enfeksiyonu üzerindeki etkilerine odaklanılmıştır.Sonuç ve Tartışma: Yenilebilir bir mantar olan Lentinula edodes'in asetillenmiş α-1,4-glukanlar bakımından zenginleştirilmiş, standartlaştırılmış, kültürlenmiş bir özütü olan AHCC® sahip olduğu çeşitli farmakolojik etkileri nedeni ile HPV tedavisinde öne çıkan alternatif tedavi seçenekleri arasında yer almaktadır. Yapılan preklinik ve klinik çalışmalar, AHCC®’nin bağışıklık sistemini destekleyerek HPV tedavisi için umut veren yeni bir seçenek olabileceğini göstermektedir.
目的:人类乳头瘤病毒(HPV)是一种严重的公共卫生问题,因为它是最常见的性传播病毒感染,根据亚型的不同,可在皮肤和粘膜上引起疣和癌的形成。如今,治疗人乳头瘤病毒的方法有多种,但都不能根除疾病,只能去除向外生长的疣体,改善症状。除了这些治疗方法外,有研究表明,使用各种支持免疫系统的天然产品也可能对治疗人乳头瘤病毒有益。虽然蘑菇提取物对免疫系统的确切影响尚未完全阐明,但多年来,世界各地一直在使用蘑菇提取物治疗各种健康问题。本综述主要探讨蘑菇提取物 AHCC® 对人类乳头瘤病毒感染的影响:AHCC®是一种富含乙酰化α-1,4-葡聚糖的标准化食用菌(Lentinula edodes)培养提取物,因其各种药理作用而成为治疗人乳头瘤病毒的重要替代疗法之一。临床前和临床研究表明,AHCC® 可以支持免疫系统,是治疗人乳头瘤病毒的一种很有前景的新选择。
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引用次数: 0
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Ankara Universitesi Eczacilik Fakultesi Dergisi
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