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Editorial Note for Journal of Bioequivalence & Bioavailability 《生物等效性与生物利用度杂志》编辑说明
Pub Date : 2020-01-01 DOI: 10.35248/0975-0851.20.12.397
F. Sorgel
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引用次数: 0
Editorial Highlights for Journal of Bioequivalence & Bioavailability 《生物等效性与生物利用度杂志》编辑要点
Pub Date : 2020-01-01 DOI: 10.35248/0975-0851.20.12.394
H. Sahoo
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引用次数: 0
Tulsi: The Queen of Medicinal Herbs 图丝:草药女王
Pub Date : 2020-01-01 DOI: 10.35248/0975-0851.20.12.407
Riddhi Patel
Tulsi has got the great medicinal value. Studies have also shown Tulsi to be effective for diabetes, by reducing blood glucose levels. The same study showed significant reduction in total cholesterol levels with Tulsi. Another study showed that Tulsi's beneficial effect on blood glucose levels is due to its antioxidant properties. The Rama Tulsi is the effective remedy for the severe acute Respiratory Syndrome. Juice of its leaves gives relief in cold, fever, bronchitis and cough. Tulsi oil is also used as the ear drop. Tulsi helps in curing malaria. It is very effective against indigestion, headache, hysteria, insomnia and cholera. The fresh leaves of Tulsi are taken by the millions of people every day. For over the centuries Tulsi (the queen of herbs) has been known for its remarkable healing properties. Modern scientific research offers impressive evidence that Tulsi reduces stress, enhances stamina, relieves inflammation, lowers cholesterol, eliminates toxins, protects against radiation, prevents gastric ulcers, lowers fevers, improves digestion and provides a rich supply of antioxidants and other nutrients. Tulsi is especially effective in supporting the heart, blood vessels, liver and lungs and also regulates blood pressure and blood sugar. Recent studies suggest that Tulsi may be a COX-2 inhibitor, like many modern painkillers, due to its high concentration of eugenol (1-hydroxy-2- methoxy-4- allylbenzene). The anti-flu property of Tulsi has been discovered by medical experts across the world quite recently. Tulsi improves the body's overall defence mechanism including its ability to fight viral diseases.
图尔丝有很大的药用价值。研究还表明,Tulsi通过降低血糖水平对糖尿病有效。同样的研究表明,服用Tulsi后,总胆固醇水平显著降低。另一项研究表明,Tulsi对血糖水平的有益作用是由于它的抗氧化特性。Rama Tulsi是治疗严重急性呼吸系统综合症的有效药物。其叶子的汁液可以缓解感冒、发烧、支气管炎和咳嗽。Tulsi油也被用作滴耳液。图尔西有助于治疗疟疾。它对消化不良、头痛、歇斯底里、失眠和霍乱都很有效。图尔西的新鲜树叶每天被数百万人采摘。几个世纪以来,图尔西(草药女王)以其非凡的治疗特性而闻名。现代科学研究提供了令人印象深刻的证据:图尔西可以减轻压力,增强耐力,缓解炎症,降低胆固醇,消除毒素,防止辐射,预防胃溃疡,降低发烧,改善消化,并提供丰富的抗氧化剂和其他营养物质。Tulsi在支持心脏、血管、肝脏和肺部方面特别有效,还能调节血压和血糖。最近的研究表明,由于其含有高浓度的丁香酚(1-羟基-2-甲氧基-4-烯丙基苯),Tulsi可能像许多现代止痛药一样是一种COX-2抑制剂。Tulsi的抗流感特性是最近被世界各地的医学专家发现的。Tulsi改善了身体的整体防御机制,包括对抗病毒性疾病的能力。
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引用次数: 5
Model-Based Elaboration of a Limited Sampling Strategy in the Bioequivalence Assessment of Highly Variable Dabigatran 高变量达比加群生物等效性评价中有限采样策略的基于模型的阐述
Pub Date : 2020-01-01 DOI: 10.35248/0975-0851.20.12.396
Cass, re Legault, Jun Yu Li
Background: The bioequivalence (BE) assessment of generic (Test) and brand name (Reference) formulations of drugs with steep exposure-response relationships exhibiting high pharmacokinetic (PK) variability such as dabigatran represent an expensive challenge for pharmaceutical companies. Supported by the population pharmacokinetics (pop-PK) approach, the present article investigates modelling potential to assess BE using a reduced number of blood samples. Methods: Pop-PK models for the Reference and Test formulations were developed retrospectively using standard modeling techniques for a BE study of dabigatran. Reduced sampling scenarios were selected and the developed pop- PK models were refitted on each dataset for the respective formulations. These models were simulated to generate virtual PK profiles to be tested with the standard BE criteria, in order to identify the scenarios maintaining the original BE conclusions with the least samples required. Results: The BE study original data was best described as a pop-PK model presenting two compartments with first order elimination and absorption, as well as an absorption lag time. Sex was identified as a significant covariate with impact on bioavailability. Using a rational sampling selection procedure under the framework of modeling and simulation, the results proved that the BE verdict could be maintained with only five of the 20 original blood samples using the current regulatory BE standards and criteria. Conclusion: We conclude that the pop-PK model-based BE assessment can be an efficient tool for aiding the BE assessment of dabigatran by significantly reducing the number of samples required, and consequently lower trial costs and increase benefits for enrolled participants.
背景:对达比加群等具有高药代动力学(PK)变异性的暴露-反应关系的仿制(试验)和品牌(参考)制剂进行生物等效性(BE)评估,对制药公司来说是一项昂贵的挑战。在人群药代动力学(pop-PK)方法的支持下,本文研究了使用减少血液样本数量来评估BE的建模潜力。方法:采用标准建模技术对达比加群的BE研究回顾性地开发了参考配方和试验配方的Pop-PK模型。选择减少的采样场景,并在每个数据集上针对各自的配方调整开发的pop- PK模型。通过对这些模型进行模拟,生成虚拟的PK配置文件,然后用标准的be标准进行测试,以便用最少的样本确定维持原始be结论的场景。结果:BE研究的原始数据被最好地描述为pop-PK模型,该模型呈现两个区室,具有一级消除和吸收,以及吸收滞后时间。性别被确定为影响生物利用度的重要协变量。在建模和仿真的框架下,采用合理的抽样选择程序,结果证明,使用现行的监管BE标准和标准,20份原始血液样本中只有5份可以维持BE判决。结论:我们得出结论,基于pop-PK模型的BE评估可以有效地帮助达比加群的BE评估,显著减少所需的样本数量,从而降低试验成本并增加入组参与者的收益。
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引用次数: 1
Non-linear Mixed Effects Modeling and Simulation for Exploring VariabilitySources in Dissolution Curves: A BCS Class II Case Example 探索溶解曲线变异性来源的非线性混合效应建模与模拟:一个BCS II类案例示例
Pub Date : 2020-01-01 DOI: 10.35248/0975-0851.20.12.406
E. Karatza, V. Karalis
Purpose: Irbesartan is a BCS class II compound that exhibits pH– and buffer capacity–dependent dissolution behavior. The aim of this study was to apply non-linear mixed effects modelling on dissolution data of two immediate release products containing Irbesartan in order to characterize and quantify the sources of inter-dissolution profile variability. Methods: Nonlinear mixed effects modelling was applied to describe the dissolution curves obtained for Irbesartan in three different pH-value media (1.2, 4.5, 6.8) with two different products (reference product: Aprovel® and a generic test product). Simulations performed and the impact of inter-dissolution variability was assessed. Results: The % Irbesartan dissolved to time was found to follow a Weibull distribution. Τhe population scale parameter was estimated 0.252 and the shape parameter was estimated 0.706. The pH-value of the dissolution medium was found to significantly affect the scale parameter, while the formulation was found to affect the shape parameter. Simulations showed that probably some discrepancies in the in vivo performance of the two products can be expected. Conclusion: Through this case study the applicability and usefulness of nonlinear mixed effects modelling in oral drug formulation was highlighted and resides in its ability to identify and quantify sources of variability.
目的:厄贝沙坦是一种BCS II类化合物,具有pH和缓冲容量依赖的溶解行为。本研究的目的是对两种含厄贝沙坦的速释产品的溶出度数据应用非线性混合效应模型,以表征和量化内部溶出度变化的来源。方法:采用非线性混合效应模型描述厄贝沙坦在三种不同ph值介质(1.2、4.5、6.8)和两种不同产品(参考产品:阿普罗维尔®和通用测试产品)中的溶出曲线。进行了模拟并评估了溶解间变异性的影响。结果:厄贝沙坦随时间溶出的百分比服从威布尔分布。Τhe总体尺度参数估计为0.252,形状参数估计为0.706。发现溶解介质的ph值对粒径参数有显著影响,而配方对粒径参数有显著影响。模拟结果表明,这两种产品的体内性能可能存在一些差异。结论:通过本案例研究,强调了非线性混合效应模型在口服药物配方中的适用性和实用性,并指出其识别和量化变异性来源的能力。
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引用次数: 0
COVID-19 Clinical Trials in China COVID-19在中国的临床试验
Pub Date : 2020-01-01 DOI: 10.35248/0975-0851.20.12.409
F. Sorgel
EDITORIAL This article expects to sum up the vital characteristics of registered trials of 2019 novel coronavirus (COVID-19), as far as their spatial and fleeting dispersions, sorts of plan and intercessions, and patient qualities among others. A far reaching search of the enrolled COVID-19 trials has been performed on stages including ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (WHO Chinese Clinical Trials Registry (CHiCTR), Australian Clinical Trials Registry, Britain's National Research Register Current Control Trials (CCT), and Glaxo Smith Kline Register. Preliminaries enlisted at the initial two months of the COVID-19 flare-up are incorporated, without language limitations. For each examination, the enrollment data, study plan, and director data are gathered and summed up.
本文旨在总结2019年新型冠状病毒(COVID-19)注册试验的重要特征,包括它们的空间和短暂分散,各种计划和代祷,以及患者素质等。在ClinicalTrials.gov、世卫组织国际临床试验注册平台(世卫组织中国临床试验注册中心(CHiCTR))、澳大利亚临床试验注册中心、英国国家研究注册中心(CCT)和葛兰素史克注册中心等多个平台对已登记的COVID-19试验进行了广泛检索。在COVID-19爆发的最初两个月招募的初步人员被纳入,没有语言限制。对于每次考试,收集和总结招生数据、学习计划和主任数据。
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引用次数: 0
Medicines that are Biologicals, or maybe not: The Strange Case of Teriparatide Forsteo® and its Copy Drugs 生物制剂,或可能不是:特立帕肽Forsteo®及其仿制药的奇怪案例
Pub Date : 2020-01-01 DOI: 10.35248/0975-0851.20.12.395
D. Pilunni, P. Navarra
Medicines that are Biologicals, or Maybe Not: The Strange Case of Teriparatide Forsteo® and its Copy Drugs Daniela Pilunni1, Pierluigi Navarra2* Post-graduate School of Hospital Pharmacy, ‘La Sapienza’ University, Rome, Italy; Department of Healthcare Surveillance and Bioethics, Section of Pharmacology, Catholic University Medical School, Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy
药物是生物制品,或者可能不是:Teriparatide Forsteo®及其仿制药的奇怪案例Daniela Pilunni1, Pierluigi Navarra2*意大利罗马“La Sapienza”大学医院药学研究生院;天主教大学医学院药理学部卫生保健监测和生物伦理学系,A大学政治基金会,意大利罗马Gemelli IRCCS
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引用次数: 1
The Effect of Chemical Modifications of Chitosan on Intestinal Permeability and Oral Bioavailability of Carbamoylphosphonate JS403 壳聚糖化学修饰对氨基膦酸盐JS403肠通透性和口服生物利用度的影响
Pub Date : 2020-01-01 DOI: 10.35248/0975-0851.20.12.392
Reut Bitton-Dotan, J. Bohrisch, C. Schmidt, Marina Tsuriel, R. P. Tulichala, E. Breuer, R. Reich, A. Hoffman, J. Storsberg
JS403, Carbamoylphosphonate molecule, is a promising drug candidate with anti-metastatic activity. The polarity and water solubility of JS403 evolve from the phosphonate moiety that is ionized at physiologic pH. JS403 is regarded as a BCS class III molecule, and exhibit poor absolute oral bioavailability of less than 1%. The aim of this investigation is to identify proper chitosan based absorption enhancer compound(s) that upon oral co-administration with JS403 which would enhance its bioavailability. To determine the optimal properties of the chitosan derivative (CD), 11 relevant compounds were synthesized, each with different attribute, and their impact on the intestinal permeability of JS403 was examined in-vitro using the CaCO2 monolayer model. Then, the oral bioavailability of JS403 coadministered with the selected CD was examined in the freely moving rat model. The in-vitro study identified two leading trimethyl CD, KC13, (85% deacetylation, MW 20,000 g/mol and 66% trimethylation) and a novel derivative of hydroxypropyl chitosan KHC2 (trimethylation 71%) increased JS403 permeability in 2 and 10 folds, respectively. Similar permeability results were obtained when the same chitosan derivatives were coadministered with atenolol, another BSCIII drug. The paracellular absorption mechanism of these BCS III compounds was ascertained using palmitoyl carnitine as positive control. The pharmacokinetic investigation, following gavage coadministration with either KC13 or KHC2, showed a significant increase in JS403 oral AUC of 200%. The in-vitro permeation data correlated with the oral bioavailability outcomes. The relatively modest enhancement (~2 folds) of the chitosan derivatives in-vivo is anticipated as their effect on the enterocytes integrity and tight junction (TJ) need to be moderate. This is required because their noninvasive and reversible impact that is demanded in case of multiple treatment.
氨基膦酸盐分子JS403是一种具有抗转移活性的有前景的候选药物。JS403的极性和水溶性由生理ph电离的膦酸盐部分演变而来。JS403被认为是BCS III类分子,绝对口服生物利用度低于1%。本研究的目的是确定合适的壳聚糖基吸收促进剂,与JS403口服共给药,以提高其生物利用度。为了确定壳聚糖衍生物(CD)的最佳性能,我们合成了11种具有不同属性的相关化合物,并利用CaCO2单层模型体外研究了它们对JS403肠道通透性的影响。然后,在自由活动大鼠模型中检测JS403与所选CD共给药的口服生物利用度。体外研究发现,两种领先的三甲基壳聚糖KC13(85%去乙酰化,分子量20,000 g/mol, 66%三甲基化)和一种新型羟丙基壳聚糖衍生物KHC2(三甲基化71%)分别使JS403的通透性提高了2倍和10倍。当相同的壳聚糖衍生物与另一种BSCIII药物阿替洛尔共同施用时,获得了类似的通透性结果。以棕榈酰肉碱为阳性对照,确定了这些BCS III化合物的细胞旁吸收机制。药代动力学研究显示,与KC13或KHC2共同灌胃后,JS403口服AUC显著增加200%。体外渗透数据与口服生物利用度结果相关。由于壳聚糖衍生物对肠细胞完整性和紧密连接(TJ)的影响需要适度,因此预计其在体内的增强作用相对适度(约2倍)。这是必需的,因为在多次治疗的情况下,它们的无创和可逆影响是必需的。
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引用次数: 3
Covid-19 Vaccine Development Covid-19疫苗研制
Pub Date : 2020-01-01 DOI: 10.35248/0975-0851.20.12.408
F. Sorgel
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引用次数: 61
Crude Edible Fig (Ficus carica) Leaf Extract Prevents Diethylstilbestrol (DES)-Induced DNA Strand Breaks in Single-Cell Gel Electrophoresis (SCGE)/Comet Assay: Literature Review and Pilot Study 食用无花果(Ficus carica)粗叶提取物在单细胞凝胶电泳(SCGE)/彗星分析中防止己烯雌酚(DES)诱导的DNA链断裂:文献综述和中试研究
Pub Date : 2019-04-01 DOI: 10.35248/0975-0851.19.11.389
Alrena V. Lightbourn, Ronald D. Thomas
Fig (Ficus carica) trees are among the oldest plants on earth. The chemopreventive properties of constituent polyphenols and fiber that implicate figs in having a functional role in averting cancer have not been fully elucidated. We therefore hypothesized that fig leaf extract would inhibit (or attenuate) DES-induced DNA single-strand breakage in MCF10A human breast epithelial cells. To test this hypothesis, MCF10A cells were treated with DES (1, 10, 100 μM), crude fig leaf extract (5, 10, 15 μL), or concomitant doses of DES (100 μM)/fig leaf extract (5, 10, 15 μL). The cells were analyzed for DNA strand breakage using the SCGE/COMET assay with mean olive tail moment as a marker of DNA damage. DES induced DNA strand breaks at all treatment levels compared to DMSO and non-treatment controls. DES at concentrations of 1, 10, and 100 μM produced mean olive tail moments of 1.2082 (177.6%), 1.2702 (186.7%), and 1.1275 (165.7%), respectively, which were statistically significantly (p<0.05) higher than the DMSO control value (0.6803). Exposure to fig leaf extract produced no DNA damage. Rather, a desirable dose-dependent reduction in DES-induced DNA strand breaks was observed. Composite treatment of MCF10A cells with DES and fig leaf extract attenuated DES-induced DNA strand breaks. Taken together, these results suggest a potential mechanism for cancer chemoprevention. Additional studies are necessary to identify relevant active ingredients, confirm the mechanism of action, and further elucidate the therapeutic potential of fig leaf extract for early-stage breast cancer chemoprevention.
无花果树是地球上最古老的植物之一。无花果的成分多酚和纤维在预防癌症方面的化学预防作用尚未完全阐明。因此,我们假设无花果叶提取物可以抑制(或减弱)des诱导的MCF10A人乳腺上皮细胞DNA单链断裂。为了验证这一假设,我们分别用DES(1、10、100 μM)、粗无花果叶提取物(5、10、15 μL)或DES (100 μM)/无花果叶提取物(5、10、15 μL)同时处理MCF10A细胞。使用SCGE/COMET分析细胞的DNA链断裂,平均橄榄尾力矩作为DNA损伤的标记。与DMSO和非处理对照相比,DES在所有处理水平均诱导DNA链断裂。DES浓度为1、10和100 μM时,平均橄榄尾矩分别为1.2082(177.6%)、1.2702(186.7%)和1.1275(165.7%),高于DMSO对照值(0.6803),差异有统计学意义(p<0.05)。暴露在无花果叶提取物中不会产生DNA损伤。相反,观察到des诱导的DNA链断裂的理想剂量依赖性减少。DES和无花果叶提取物复合处理MCF10A细胞可减弱DES诱导的DNA链断裂。综上所述,这些结果提示了癌症化学预防的潜在机制。需要进一步的研究来确定相关的有效成分,确认其作用机制,并进一步阐明无花果叶提取物对早期乳腺癌化学预防的治疗潜力。
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引用次数: 6
期刊
Journal of Bioequivalence & Bioavailability
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