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Therapeutic effects of stevia aqueous extract alone or in combination with metformin in induced polycystic ovary syndrome rats: Gene expression, hormonal balance, and metabolomics aspects. 甜叶菊水提取物单独或与二甲双胍联合使用对诱导多囊卵巢综合征大鼠的治疗效果:基因表达、激素平衡和代谢组学方面。
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-23 DOI: 10.1016/j.pharma.2024.08.008
A Saedi, S Zarei, M Vatanparast, M R Hajizadeh, R Hosseiniara, O S Esmaeili, M Mohammad-Sadeghipour, Z Mirzaei, M Mahmoodi

Objectives: This study aimed to assess the individual and combined effects of SAE and Met on the expression of genes related to insulin signaling, oxidative stress, hormonal imbalance, insulin resistance, and dyslipidemia in rats with induced PCOS.

Methods: The estrous cycle of 50 adult Wistar female rats was monitored through vaginal smears. Subsequently, the rats were randomly assigned into five groups of 10, including control (receiving 1ml of carboxymethyl cellulose for 49 days), induction (letrozole at 1mg/kg/d for 21 days), SAE, Met, and SAE/Met. SAE and Met were orally administered at doses of 400mg/kg/d and 250mg/kg/d on day 22 and continued for an additional 28 days. Vaginal smears were analyzed, and gene expression levels of GLUT4, SIRT1, TNF-α, and INSR were evaluated using RT-qPCR. Antioxidant parameters were assessed using detection kits.

Results: Treatment with SAE and Met restored a regular estrous cycle pattern in PCOS rats. Furthermore, SAE and Met treatment improved hormonal balance, dyslipidemia, and hyperglycemia in the rats. Administration of SAE and Met significantly elevated levels of antioxidant enzymes SOD and GPx in ovarian tissue (P<0.001). Additionally, mRNA levels of GLUT4, SIRT1, and INSR were significantly increased in ovarian tissue following SAE and Met treatment, while TNF-α gene expression decreased significantly (P<0.0001).

Conclusion: The findings suggest that SAE and Met aqueous extract exert protective effects on letrozole-induced PCOS in rats by modulating gene expression associated with insulin signaling and oxidative stress.

研究目的本研究旨在评估SAE和Met对诱导多囊卵巢综合征大鼠胰岛素信号转导、氧化应激、内分泌失调、胰岛素抵抗和血脂异常相关基因表达的单独和联合影响:方法:通过阴道涂片监测50只成年Wistar雌性大鼠的发情周期。随后,大鼠被随机分为5组,每组10只,包括对照组(接受1毫升羧甲基纤维素,共49天)、诱导组(来曲唑,1毫克/千克/天,共21天)、SAE组、Met组和SAE/Met组。第22天开始口服SAE和Met,剂量分别为400毫克/千克/天和250毫克/千克/天,并持续28天。对阴道涂片进行分析,并使用 RT-qPCR 评估 GLUT4、SIRT1、TNF-α 和 INSR 的基因表达水平。使用检测试剂盒评估了抗氧化参数:结果:用SAE和Met治疗后,多囊卵巢综合征大鼠恢复了正常的发情周期模式。此外,SAE 和 Met 治疗还改善了大鼠的激素平衡、血脂异常和高血糖。服用 SAE 和 Met 能明显提高卵巢组织中抗氧化酶 SOD 和 GPx 的水平(PC 结论:研究结果表明,SAE 和 Met 能提高卵巢组织中抗氧化酶 SOD 和 GPx 的水平:研究结果表明,SAE和Met水提取物通过调节与胰岛素信号传导和氧化应激相关的基因表达,对来曲唑诱导的多囊卵巢综合征大鼠具有保护作用。
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引用次数: 0
Risk analysis applied to the process of managing medical single use devices in a hospital pharmacy department. 将风险分析应用于医院药剂科的医疗器械管理过程。
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-22 DOI: 10.1016/j.pharma.2024.08.006
Aymen Ben Salem, Fatma Sellami, Ahlem Ben Cheikh Brahim, Yosr Krichen, Aimen Abbassi

Introduction: During the COVID-19 pandemic, single use medical devices' supply (SUMD) was marked by repetitive and unforeseen interruptions. The present study aimed to determine the risks related to the processes of management of medical devices in our CHU according to a method of failure mode, effect and criticality analysis (FMECA).

Methods: Qualified healthcare professionals were recruited to form a multidisciplinary consensus committee. By analyzing the process map, all failure modes, causes and consequences were identified through brainstorming meetings. They were then classified taking into account the criticality index (CI) calculated according to three parameters: frequency, severity, and detectability. The prioritization was carried out by considering the mean and the median values of the CI as limits. Corrective and preventive actions were then proposed.

Results: A total of 49 failure modes were identified, accumulating 4466 criticality points. The most critical step is that relating to the inter-depot order with a CI equal to 783 points. An action plan was developed, allows us to control 64% of the overall criticality of the risks linked to the process. Three main lines of action have been proposed: continuous training, especially for managerial and administrative tasks, logistical improvement (architectural reorganization and implementation of systems for securing the circuit of SUMDs) and support for the digitization of hospital pharmacy.

Conclusion: The FMECA is a consensual method, which makes it possible to propose actions in order to reduce the risks linked to the process of managing medical devices. Optimizing the estimation of needs, strengthening communication with stakeholders and securing the circuit are essential to guarantee the availability of SUMDs for the benefit of the patient.

导言:在 COVID-19 大流行期间,一次性使用医疗器械(SUMD)的供应出现了反复和不可预见的中断。本研究旨在根据失效模式、影响和关键性分析(FMECA)方法,确定本医疗中心医院医疗器械管理流程的相关风险:方法:招募合格的医护人员组成多学科共识委员会。通过分析流程图,在头脑风暴会议上确定了所有失效模式、原因和后果。然后,根据频率、严重程度和可探测性三个参数计算出的关键性指数(CI)对它们进行分类。将 CI 的平均值和中位值作为界限,对其进行优先排序。然后提出了纠正和预防措施:结果:共确定了 49 种故障模式,累计 4466 个关键点。最关键的步骤是与工厂间订单有关的步骤,其临界点为 783 点。制定的行动计划使我们能够控制与流程相关的风险中 64% 的总体临界点。我们提出了三条行动主线:持续培训,尤其是管理和行政任务方面的培训;后勤改进(结构重组和实施系统,以确保 SUMDs 的线路安全);以及支持医院药房的数字化:FMECA 是一种协商一致的方法,可以提出行动建议,以降低与医疗设备管理过程相关的风险。优化需求评估、加强与利益相关者的沟通以及确保电路安全,对于保证医疗设备的可用性以造福患者至关重要。
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引用次数: 0
Harmonization of regulatory frameworks for medical devices in BRICS countries: A path to enhanced trade and investment. 金砖国家医疗器械监管框架的协调:加强贸易和投资之路。
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-22 DOI: 10.1016/j.pharma.2024.08.007
Himanshu Pawar, Mital Patel

The study is designed to advocate for a harmonized medical device regulatory framework throughout the BRICS countries with a view to facilitating trade, attracting investments and safeguarding patients' health. The development of the medical devices industry in BRICS countries is impeded by a lack of standardized regulation. A harmonized framework would facilitate the approval process, promotion of innovation and wider access for patients to modern medical technologies. The paper analyses existing regulatory frameworks for medical devices in BRICS countries and identifies their strengths and weaknesses. Specific measures to harmonize such as standardization of technology, interoperability and the implementation of transparent licensing procedures are also proposed. The study indicates that a joint committee should be set up to supervise legal harmonization, standardization of classification and development of specific technical specifications. It also provides information about the regulatory framework in different countries, such as Brazil, Russia, India, China and South Africa, on classification of medical devices. Report emphasizes the need for a harmonized regulatory framework to rapidly introduce new healthcare technologies. It suggests that the BRICS countries can create a more conducive environment for the medical device industry, ultimately benefiting patients, manufacturers and the overall healthcare system by aligning their legislation.

这项研究旨在倡导在金砖五国建立统一的医疗器械监管框架,以促进贸易、吸引投资和保障患者健康。缺乏标准化的监管阻碍了金砖国家医疗器械行业的发展。一个统一的框架将促进审批程序,推动创新,让患者更广泛地获得现代医疗技术。本文分析了金砖国家现有的医疗器械监管框架,并指出了其优缺点。还提出了具体的协调措施,如技术标准化、互操作性和实施透明的许可程序。研究指出,应成立一个联合委员会来监督法律协调、分类标准化和具体技术规格的制定。报告还介绍了巴西、俄罗斯、印度、中国和南非等不同国家在医疗器械分类方面的监管框架。报告强调有必要建立统一的监管框架,以快速引入新的医疗保健技术。报告建议,金砖国家可以通过统一立法,为医疗器械行业创造更有利的环境,最终使患者、制造商和整个医疗系统受益。
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引用次数: 0
Évaluation de la faisabilité du dispositif d’auto-administration des médicaments par le patient dans un centre hospitalier universitaire : audits de pratique et recommandations pour une mise en œuvre sûre [大学医院药物自助管理可行性评估:临床审计和建议]。
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-21 DOI: 10.1016/j.pharma.2024.08.004
Cyril Baudrier , Victoire Petitcuenot , Nacima Oussedik , William Champeau , Rouba Alarab , Anne-Laure Lefebvre , Yara Rahma , Cecile Bottois , Ornella Conort
<div><div>En 2022, la HAS a émis des recommandations sur l’auto-administration des médicaments, destinée aux patients volontaires en hospitalisation, sous accord médical. L’objectif de notre étude est d’évaluer les pratiques liées à la gestion des médicaments dans notre établissement afin de proposer des recommandations pour une mise en œuvre sûre du dispositif d’auto-administration des médicaments. Une étude monocentrique prospective a été menée entre janvier et juin 2023. Deux audits ont été réalisés auprès des patients et des infirmier(e)s à l’aide de questionnaires basés sur les recommandations de la HAS. Sur un total de 207 patients, avec un âge moyen de 59,6 ans, 56 % étaient favorables à gérer les traitements initiés à l’hôpital. Parmi ceux ayant des traitements habituels, 62 % étaient favorables pour continuer à les gérer à l’hôpital. Dans les unités d’hospitalisation de semaine, 92 % des patients étaient favorables à la gestion de leurs traitements habituels, et 75 % à ceux initiés à l’hôpital. Parmi les 26 infirmier(e)s interrogé(e)s, 71 % ont noté l’autonomie des patients pour la prise médicamenteuse dans les transmissions narratives, 88 % ont vérifié la prise médicamenteuse en auto-administration, et 96 % l’ont tracée informatiquement. Le dispositif d’auto-administration des médicaments est envisageable dans notre établissement, notamment dans les unités d’hospitalisation de semaine avec des patients ayant une bonne connaissance de leurs traitements. Actuellement, les infirmier(e)s évaluent et assurent la traçabilité de l’autonomie du patient sans outils spécifiques. Pour garantir le succès de cette nouvelle approche, une collaboration entre les professionnels de santé est essentielle, avec un rôle central du pharmacien.</div></div><div><div>The French Health Authority recently published guidelines about patient self-administration of medications for voluntary hospitalized patients under medical supervision. This study aimed to assess medication management practices in our hospital and provide recommendations for self-administration medication. A prospective monocentric study was performed from January to June 2023, involving patient and nurse surveys based on the guidelines from the French Health Authority. A total of 207 patients participated in the survey, with a mean age of 59.6<!--> <!-->years. Among them, 56% were inclined to self-manage treatments initiated during hospitalization. Among patients with regular treatments, 62% were inclined to self-manage them in the hospital. In weekday hospitalization units, 92% of patients were inclined to self-manage their regular treatments, and 75% of those initiated during hospitalization. Among the 26 surveyed nurses, 71% reported patient autonomy for taking drugs in narrative transmissions, and 88% verified medication intake through self-administration, while 96% digitally traced it. The concept of self-administration of medication appears promising, especially within weekday hospitalizat
法国卫生局最近发布了关于自愿住院患者在医生指导下自行用药的指南。这项研究旨在评估我院的用药管理实践,并为患者自行用药提供建议。2023年1月至6月期间,我们根据法国卫生局的指南开展了一项前瞻性单中心研究,对患者和护士进行了问卷调查。其中,56%的患者倾向于自我管理住院期间开始的治疗。在定期接受治疗的患者中,62%的人倾向于在住院期间自行管理治疗。在平日住院的病房中,92% 的患者倾向于自我管理常规治疗,75% 的患者倾向于在住院期间开始自我管理治疗。在接受调查的 26 名护士中,71% 的护士在叙述性转述中报告了病人服药的自主性,88% 的护士通过自我服药核实了药物摄入量,96% 的护士通过数字追踪核实了药物摄入量。目前,护士在评估患者自主性时并没有特定的监测工具。医护人员之间的合作对于这种创新方法的成功至关重要,而药剂师则扮演着核心角色。
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引用次数: 0
Cardiovascular disease and thrombosis: Intersections with the immune system, inflammation, and the coagulation system. 心血管疾病与血栓形成:与免疫系统、炎症和凝血系统的交集。
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-17 DOI: 10.1016/j.pharma.2024.08.005
Shivam Rajput, Rishabha Malviya, Saurabh Srivastava, Irfan Ahmad, Safia Obaidur Rab, Prerna Uniyal

The coagulation and immune system, both essential physiological systems in the human body, are intricately interconnected and play a critical role in determining the overall health of patients. These systems collaborate via various shared regulatory pathways, such as the Tissue Factor (TF) Pathway. Immunological cells that express TF and generate pro-inflammatory cytokines have the ability to affect coagulation. Conversely, coagulation factors and processes have a reciprocal effect on immunological responses by stimulating immune cells and regulating their functions. These interconnected pathways play a role in both preserving well-being and contributing to a range of pathological disorders. The close relationship between blood clotting and inflammation in the development of vascular disease has become a central focus of clinical study. This research specifically examines the crucial elements of this interaction within the contexts of cardiovascular disease and acute coronary syndrome. Tissue factor, the primary trigger of the extrinsic coagulation pathway, has a crucial function by inducing a proinflammatory reaction through the activation of coagulation factors. This, in turn, initiates coagulation and subsequent cellular signalling pathways. Protease-activated receptors establish the molecular connection between coagulation and inflammation by interacting with activated clotting factors II, X, and VII. Thrombosis, a condition characterised by the formation of blood clots, is the most dreaded consequence of cardiovascular disorders and a leading cause of death globally. Consequently, it poses a significant challenge to healthcare systems. Antithrombotic treatments efficiently target platelets and the coagulation cascade, but they come with the inherent danger of causing bleeding. Furthermore, antithrombotics are unable to fully eliminate thrombotic events, highlighting a treatment deficiency caused by a third mechanism that has not yet been sufficiently addressed, namely inflammation. Understanding these connections may aid in the development of novel approaches to mitigate the harmful mutual exacerbation of inflammation and coagulation. Gaining a comprehensive understanding of the intricate interaction among these systems is crucial for the management of diseases and the creation of efficacious remedies. Through the examination of these prevalent regulatory systems, we can discover novel therapeutic approaches that specifically target these complex illnesses. This paper provides a thorough examination of the reciprocal relationship between the coagulation and immune systems, emphasising its importance in maintaining health and understanding disease processes. This review examines the interplay between inflammation and thrombosis and its role in the development of thrombotic disorders.

凝血系统和免疫系统都是人体重要的生理系统,它们之间有着错综复杂的联系,在决定患者整体健康方面发挥着至关重要的作用。这些系统通过组织因子(TF)途径等各种共享调控途径相互协作。表达 TF 并产生促炎细胞因子的免疫细胞能够影响凝血功能。相反,凝血因子和凝血过程通过刺激免疫细胞并调节其功能,对免疫反应产生相互影响。这些相互关联的途径既能维护人体健康,也能导致一系列病理紊乱。凝血和炎症在血管疾病发展过程中的密切关系已成为临床研究的核心重点。这项研究特别探讨了心血管疾病和急性冠状动脉综合征中这种相互作用的关键因素。组织因子是外凝血途径的主要触发因子,其关键作用是通过激活凝血因子诱发促炎反应。这反过来又启动了凝血和随后的细胞信号通路。蛋白酶活化受体通过与活化的凝血因子 II、X 和 VII 相互作用,建立了凝血与炎症之间的分子联系。血栓形成是心血管疾病最可怕的后果,也是全球死亡的主要原因。因此,它给医疗保健系统带来了巨大挑战。抗血栓治疗能有效地针对血小板和凝血级联反应,但也有引起出血的固有危险。此外,抗血栓药物无法完全消除血栓事件,这凸显了尚未充分解决的第三个机制(即炎症)造成的治疗缺陷。了解这些联系有助于开发新的方法,减轻炎症和凝血相互加重的危害。全面了解这些系统之间错综复杂的相互作用对于疾病的治疗和创造有效的疗法至关重要。通过研究这些普遍存在的调节系统,我们可以发现专门针对这些复杂疾病的新型治疗方法。本文深入探讨了凝血系统和免疫系统之间的相互关系,强调了它们在维持健康和了解疾病过程中的重要性。这篇综述探讨了炎症与血栓形成之间的相互作用及其在血栓性疾病发展中的作用。
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引用次数: 0
Aqueous eye drop formulations: Cyclodextrins as enabling excipients 水性滴眼液配方:环糊精作为赋形剂。
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-08 DOI: 10.1016/j.pharma.2024.08.003
Frédéric Pilotaz , Thorsteinn Loftsson
Cyclodextrins are enabling pharmaceutical excipients that solubilize and stabilize drugs in aqueous formulations. Cyclodextrins possess very favorable pharmacokinetic and toxicological profiles and are commonly used in marketed drug products for oral and parenteral administration. However, their use in ophthalmic products is still very limited. Cyclodextrins have a broad range of physical properties that are specifically appropriate for designing topical ophthalmic dosage forms. Additionally, both the regulatory and intellectual property environments have been cleared over the last years and should foster their use for designing new drugs for ophthalmic use.
Les cyclodextrines sont des excipients permettant la solubilisation et la stabilisation de médicaments dans les formes pharmaceutiques aqueuses. Les cyclodextrines possèdent des profils pharmacocinétiques et toxicologiques très favorables et sont couramment utilisées dans des médicaments commercialisés pour l’administration orale et parentérale. Toutefois, leur utilisation dans les produits ophtalmiques est encore très limitée. Les cyclodextrines possèdent un large spectre de propriétés physiques qui est particulièrement adapté pour la conception de formes pharmaceutiques à usage topique ophtalmique. Enfin, leur environnement réglementaire ainsi que celui de la propriété intellectuelle se sont éclaircis au cours des dernières années, ce qui devrait favoriser leur utilisation pour la conception de nouveaux médicaments à usage ophtalmique.
环糊精是一种有效的药用辅料,可以溶解和稳定水性制剂中的药物。环糊精具有非常有利的药代动力学和毒理学特征,常用于口服和肠外给药的上市药品中。然而,它们在眼科产品中的应用仍然非常有限。环糊精具有广泛的物理特性,特别适合设计眼科局部用药的剂型。此外,在过去几年中,环糊精的监管和知识产权环境都得到了净化,这将促进环糊精在眼科新药设计中的应用。
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引用次数: 0
Understanding the side effects of chronic silodosin administration via untargeted metabolomics approach 通过非靶向代谢组学方法了解长期服用西洛多辛的副作用
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-08 DOI: 10.1016/j.pharma.2024.08.002
Tugrul Cagri Akman , Yucel Kadioglu , Onur Senol , Beyzagul Erkayman , İsmail Cagri Aydin
<div><h3>Background</h3><div>Precision medicine, which looks for high efficacy and low toxicity in therapies, has increased in popularity with omics technology. This work aims to discover novel and low-toxicity therapy options by examining the complex relationship between silodosin-induced side effects and the metabolomic profiles associated with its administration.</div></div><div><h3>Materials and methods</h3><div>The plasma samples of the control group and silodosin-treated rats were analyzed by LC-Q-TOF-MS/MS. Employing XCMS and MetaboAnalyst software, MS/MS data processed to detect compounds and investigate metabolic pathways. MATLAB 2019b was used for data categorization and multivariate analysis. A thorough comparison of METLIN and HMDB databases revealed 41<!--> <em>m/z</em> values with significant differences between the drug-treated and control groups (<!--> <em>p</em> <<!--> <!-->0.01 and fold analysis<!--> <!-->≥<!--> <!-->1.5).</div></div><div><h3>Results</h3><div>According to multivariate data analysis, 17-<em>β</em>-estradiol, taurocholic acid, L-kynurenine, <em>N</em>-formylkynurenine, D-glutamine, L-arginine, prostaglandin H2, prostaglandine G2, 15-keto-prostaglandin E2, calcidiol, thromboxane A2, 5′-methylthioadenosine, L-methionine and <em>S</em>-adenosylmethionine levels changed significantly compared to the control group. Differences in the metabolisms of glycerophospholipid, tyrosine, phenylalanine, arachidonic acid, cysteine and methionine, and biosynthesis of phenylalanine, tyrosine, and tryptophan, and aminoacyl-tRNA have been successfully demonstrated by metabolic pathway analysis. According to this study, vitamin D, D-glutamine, and L-arginine supplements can be recommended to prevent side effects such as fatigue, intraoperative floppy iris syndrome, blurred vision, and dizziness in the treatment of silodosin. Silodosin treatment negatively affected the immune system by affecting the kynurenine and tryptophan metabolism pathways.</div></div><div><h3>Conclusions</h3><div>The study is a guide for silodosin treatments that offer low side effects and high therapeutic effect within the scope of precision medicine.</div></div><div><h3>Contexte</h3><div>La médecine de précision, qui recherche une efficacité élevée et une faible toxicité dans les thérapies, a gagné en popularité grâce à la technologie omics. Ce travail vise à découvrir de nouvelles options thérapeutiques à faible toxicité en examinant la relation complexe entre les effets secondaires induits par la silodosine et les profils métabolomiques associés à son administration.</div></div><div><h3>Matériaux et méthodes</h3><div>Les échantillons de plasma du groupe témoin et des rats traités à la silodosine ont été analysés par LC-Q-TOF-MS/MS. Les logiciels XCMS et MetaboAnalyst ont été utilisés pour traiter les données MS/MS afin d’identifier les métabolites et d’analyser les voies métaboliques. MATLAB 2019b a été utilisé pour catégoriser les données afin d’effectuer
背景:精准医疗(precision medicine)是一种追求高效、低毒的治疗方法,随着omics技术的发展而越来越受欢迎。本研究旨在通过了解西洛多辛引起的副作用与用药相关代谢组学特征之间的复杂关系,发掘创新的低毒性疗法:采用 LC-Q-TOF/MS/MS 分析对照组和西洛多辛治疗组大鼠的血浆样本。采用 LC-Q-TOF-MS/MS 分析对照组和西洛多辛治疗组大鼠的血浆样本。利用 XCMS 和 MetaboAnalyst 软件处理 MS/MS 数据,以检测化合物并研究代谢途径。MATLAB 2019b 用于数据分类和多元分析。通过全面比较 METLIN 和 HMDB 数据库,发现药物治疗组和对照组之间有 41 个 m/z 值存在显著差异(pResults:根据多元数据分析,与对照组相比,17-β-雌二醇、牛胆酸、L-犬尿氨酸、N-甲酰犬尿氨酸、D-谷氨酰胺、L-精氨酸、前列腺素 H2、前列腺素 G2、15-酮前列腺素 E2、降钙素二醇、血栓素 A2、5'-甲硫基腺苷、L-蛋氨酸和 S-腺苷蛋氨酸的水平发生了显著变化。通过代谢途径分析,成功证实了甘油磷脂、酪氨酸、苯丙氨酸、花生四烯酸、半胱氨酸和蛋氨酸的代谢以及苯丙氨酸、酪氨酸、色氨酸和氨基酰-tRNA的生物合成存在差异。根据这项研究,建议补充维生素 D、L-谷氨酰胺和 L-精氨酸,以防止西洛多辛治疗过程中出现疲劳、术中虹膜松弛综合征 IFIS、视力模糊和头晕等副作用。西洛多辛治疗通过影响犬尿氨酸和色氨酸代谢途径对免疫系统产生负面影响:该研究为西洛多辛治疗提供了指导,在精准医疗的范围内,西洛多辛治疗可提供低副作用和高疗效。
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引用次数: 0
A review on recent advancements in pharmaceutical technology transfer of tablets from an Indian perspective. 从印度角度回顾片剂制药技术转让的最新进展。
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-08 DOI: 10.1016/j.pharma.2024.08.001
Kishan Singh, Nidhi Nainwal, Havagiray R Chitme

Objective: The healthcare sector is a paramount and rapidly expanding industry in India. The pharmaceutical field in India has experienced substantial growth and transformation in recent times, making significant contributions to the global healthcare market. This comprehensive review delves into the most recent innovations in pharmaceutical technology transfer (TT), particularly in the context of tablet formulations from an Indian standpoint.

Significance: The pharmaceutical sector has grappled with various challenging issues, including the escalating costs of medications and the demand for patient-friendly products.

Methods: In this technological progress era, various cutting-edge pharmaceutical technologies, such as artificial intelligence (AI), and 3D and 4D printing, play pivotal roles in drug development. Tablets, the most promising and widely utilized dosage form worldwide, require a sophisticated approach to TT. Achieving a successful TT necessitates a dedicated team with well-defined objectives, improved documentation, and effective communication.

Results: The Indian Pharmaceutical Industry (IPI) possesses the potential to make significant contributions to the global healthcare sector. Moreover, we delve into the various phases of TT, highlighting the pivotal role of formulation development and process optimization in ensuring product quality, efficiency, and cost-effectiveness along with different models of TT. Additionally, we examine the challenges associated with TT and potential solutions, as well as the initiatives of the Indian government to bolster the Indian pharmaceutical sector's position as the "Pharmacy of the World".

Conclusion: It is concluded that there is a need to contextualize and institutionalize the tech transfer policies for successful implementation for the benefit of the global population.

目的:在印度,医疗保健行业是一个至关重要且发展迅速的行业。近来,印度制药领域经历了大幅增长和变革,为全球医疗市场做出了重大贡献。本综述从印度的角度深入探讨了制药技术转让(TT)方面的最新创新,特别是在片剂制剂方面:意义:制药行业一直在努力应对各种挑战性问题,包括不断攀升的药品成本和对患者友好型产品的需求:在这个技术进步的时代,人工智能(AI)、3D 和 4D 打印等各种尖端制药技术在药物开发中发挥着举足轻重的作用。片剂是世界上最有前途、使用最广泛的剂型,需要采用复杂的方法进行技术转换。要实现成功的 TT,就必须有一个目标明确、文档完善、沟通有效的专业团队:印度制药业(IPI)拥有为全球医疗保健行业做出重大贡献的潜力。此外,我们深入研究了 TT 的各个阶段,强调了配方开发和工艺优化在确保产品质量、效率和成本效益方面的关键作用,以及不同的 TT 模式。此外,我们还探讨了与传统工艺相关的挑战和潜在的解决方案,以及印度政府为巩固印度制药业作为 "世界药房 "的地位而采取的举措:结论:有必要将技术转让政策背景化和制度化,以便成功实施,造福全球人民。
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引用次数: 0
Enhancing drug bioavailability for Parkinson's disease: The promise of chitosan delivery mechanisms. 提高帕金森病药物的生物利用度:壳聚糖给药机制的前景。
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-31 DOI: 10.1016/j.pharma.2024.07.008
Mohammad Arshad Javed Shaikh, Gaurav Gupta, Pawan Bagiyal, Saurabh Gupta, Santosh Kumar Singh, Ramkumar Pillappan, Dinesh Kumar Chellappan, Parteek Prasher, Vikas Jakhmola, Thakur Gurjeet Singh, Harish Dureja, Sachin Kumar Singh, Kamal Dua

Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD.

帕金森病(PD)是一种广泛存在的神经退行性疾病,其特征是α-突触核蛋白(αSyn)蛋白折叠错误,这是帕金森病和其他突触核蛋白病的主要指标。在脊髓灰质炎的发病过程中,僵硬、运动障碍、静止性震颤和姿势不稳等运动症状与非运动症状并存,这些症状因人而异。这些症状源于突触和神经元的逐渐丧失,导致多个器官出现广泛的退行性病变。脑深部刺激等医疗和外科干预措施提高了帕金森病患者的整体健康水平和长期存活率。值得一提的是,这些治疗方法并不能阻止病情恶化。大脑结构复杂,存在半透膜屏障(俗称 "BBB"),这使得治疗帕金森氏症的药物输送一直是一项具有挑战性的工作。药物的低亲脂性、巨大的体积以及各种依赖 ATP 的转运机制的特殊性阻碍了其进入脑细胞的能力。本文深入探讨了基于壳聚糖(CS)的给药系统治疗帕金森病的潜力。
{"title":"Enhancing drug bioavailability for Parkinson's disease: The promise of chitosan delivery mechanisms.","authors":"Mohammad Arshad Javed Shaikh, Gaurav Gupta, Pawan Bagiyal, Saurabh Gupta, Santosh Kumar Singh, Ramkumar Pillappan, Dinesh Kumar Chellappan, Parteek Prasher, Vikas Jakhmola, Thakur Gurjeet Singh, Harish Dureja, Sachin Kumar Singh, Kamal Dua","doi":"10.1016/j.pharma.2024.07.008","DOIUrl":"10.1016/j.pharma.2024.07.008","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a widely seen neurodegenerative condition recognized by misfolded α-synuclein (αSyn) protein, a prominent indicator for PD and other synucleinopathies. Motor symptoms like stiffness, akinesia, rest tremor, and postural instability coexist with nonmotor symptoms that differ from person to person in the development of PD. These symptoms arise from a progressive loss of synapses and neurons, leading to a widespread degenerative process in multiple organs. Implementing medical and surgical interventions, such as deep brain stimulation, has enhanced individuals' overall well-being and long-term survival with PD. It should be mentioned that these treatments cannot stop the condition from getting worse. The complicated structure of the brain and the existence of a semi-permeable barrier, commonly known as the BBB, have traditionally made medication delivery for the treatment of PD a challenging endeavor. The drug's low lipophilic nature, enormous size, and peculiarity for various ATP-dependent transport mechanisms hinder its ability to enter brain cells. This article delves at the potential of drug delivery systems based on chitosan (CS) to treat PD.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874053","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
Evaluation of cilnidipine-loaded self-micro-emulsifying drug delivery system (SMEDDS) by quantification of comparative pharmacokinetic parameters using validated LC-ESI-MS/MS bioanalytical method and pharmacodynamic assessment 利用经验证的 LC-ESI-MS/MS 生物分析方法和药效学评估,通过比较药代动力学参数的定量分析,评估负载西尼地平的自微乳化给药系统 (SMEDDS)。
IF 1 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-30 DOI: 10.1016/j.pharma.2024.07.007
Kumar Anand , Pallab Mandal , Samit Karmakar , Rudranil Bhowmik , Md. Adil Shaharyar , Avishek Mandal , Arnab Sarkar , Akash De , Soumya Chakraborty , Subhabrata Ray , Manas Bhowmik , Sanmoy Karmakar
<div><h3>Objective</h3><div>Regardless of having desired therapeutic properties many of the recently approved drugs are removed from the developmental pipeline for their clinical use due to low solubility and permeability. Conventional dosage forms are found relatively unsuitable for achieving desired pharmacokinetic and pharmacodynamics profiles. Cilnidipine is 1,4 dihydropyridine derivative calcium channel blocker used for the treatment of hypertension.</div></div><div><h3>Method</h3><div>The aim and objective of this study was to develop a precise and significant method in LC-MS/MS for quantification of pharmacokinetic parameters of a cilnidipine-loaded self-micro-emulsifying drug delivery system in rat plasma and simultaneously assessed pharmacodynamic characters in comparison with the marketed cilnidipine tablet. Another potential aim of this study is to reduce the dose of the drug in order to counter the dose-dependent toxicities related to chronic use. In the present study, the parent and product ion of cilnidipine was m/z 491.3237.1.</div></div><div><h3>Result</h3><div>The plasma was extracted by protein precipitation technique. The calibration standard concentrations were 1.875, 3.75, 7.50, 15.00, 30.00, 60.00<!--> <!-->ng/mL and LLOQ, low-quality control, middle-quality control and high-quality control were 1.87, 5.62, 22.50, 45.00<!--> <!-->ng/mL, respectively. The mobile phase composition was 0.1% formic acid in Milli Q water with 10<!--> <!-->mM Ammonium acetate as an aqueous solvent and 0.1% formic acid in methanol as an organic solvent. Following oral administration of optimized formulation C<sub>max</sub> (peak plasma concentration) was achieved 21.02<!--> <!-->±<!--> <!-->3.17<!--> <!-->ng/mL at 0.866<!--> <!-->±<!--> <!-->0.11<!--> <!-->h (Tmax), whereas in the case of marketed tablet C<sub>max</sub> (peak plasma concentration) was achieved 10.16<!--> <!-->±<!--> <!-->0.89<!--> <!-->ng/mL at 0.93<!--> <!-->±<!--> <!-->0.11<!--> <!-->h (Tmax).</div></div><div><h3>Discussion</h3><div>The in-vivo characterizations of the optimized SMEDDS showed significantly better pharmacokinetic parameters in Wistar rats and showed almost 2.4 times enhanced relative bioavailability as compared to the marketed tablet of cilnidipine which was observed to be correlating to our findings with noninvasive blood pressure parameter of Wistar rats.</div></div><div><h3>Objectif</h3><div>Indépendamment de leurs propriétés thérapeutiques souhaitées, de nombreux médicaments récemment approuvés sont retirés du pipeline de développement pour leur utilisation clinique en raison de leur faible solubilité et perméabilité. Les formes posologiques conventionnelles s’avèrent relativement inadaptées pour atteindre les profils pharmacocinétiques et pharmacodynamiques souhaités. La cilnidipine est un inhibiteur calcique dérivé de la 1,4 dihydropyridine utilisé pour le traitement de l’hypertension.</div></div><div><h3>Méthode</h3><div>Le but et l’objectif de cette étude
目的:许多新近获批的药物尽管具有理想的治疗特性,但由于溶解度和渗透性较低,在临床应用中被从研发管道中剔除。西尼地平是一种 1,4-二氢吡啶衍生物钙通道阻滞剂,用于治疗高血压:本研究的目的和目标是开发一种精确、有效的 LC-MS/MS 方法,用于定量检测大鼠血浆中含西尼地平的自体微乳化给药系统的药代动力学参数,并同时评估与市场上销售的西尼地平片剂相比的药效学特征。这项研究的另一个潜在目的是减少药物剂量,以应对与长期用药有关的剂量依赖性毒性。在本研究中,西尼地平的母离子和产物离子为 m/z 491.3237.1.结果:采用蛋白沉淀技术提取血浆。标准品浓度为1.875、3.75、7.50、15.00、30.00、60.00 ng/ml,低质对照品、中质对照品和高质对照品的定量限分别为1.87、5.62、22.50、45.00ng/ml。流动相组成为 0.1% 甲酸溶于含 10mM 乙酸铵的 Milli Q 水作为水溶剂,0.1% 甲酸溶于甲醇作为有机溶剂。口服优化制剂后,在 0.866±0.11 小时(Tmax)达到 21.02±3.17 纳克/毫升的 Cmax(血浆浓度峰值),而市场上销售的片剂在 0.93±0.11 小时(Tmax)达到 10.16±0.89 纳克/毫升的 Cmax(血浆浓度峰值):优化后的 SMEDDS 在 Wistar 大鼠体内的药代动力学参数明显更好,与西尼地平的市售片剂相比,其相对生物利用度几乎提高了 2.4 倍,这与我们对 Wistar 大鼠无创血压参数的研究结果是一致的。
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引用次数: 0
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Annales pharmaceutiques francaises
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