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《Journal of pharmaceutical sciences》2023,112(8):2212-2222
For supersaturating formulations of BCS-II compounds, which by definition have high intestinal permeability, a closed USP apparatus does not provide the necessary absorptive conditions during dissolution. To address this, an artificial gut simulator (AGS) has been constructed consisting of a 2.5 mL donor compartment in which a hollow fiber-based absorption module is suspended. Drug from donor diffuses across the hollow fiber membrane to be absorbed by the continuously flowing intraluminal receiver fluid. The membrane surface area and intraluminal fluid flow rate are tuned to obtain the physiologically observed absorption rate constant for a weakly basic, poorly water-soluble model compound, ketoconazole (KTZ). Supersaturated solutions of KTZ were generated in the donor in pH 6.5 phosphate buffer by the pH-shift method in the absence (closed system, control) and presence (open system, biorelevant) of an optimally or suboptimally tuned absorption module. Drug concentrations in the donor and intraluminal fluids were determined by in-line UV spectroscopy. The presence of an absorptive sink reduced the supersaturated solution's crystallization propensity, more so in the case of the optimally tuned AGS. This study demonstrates the significance of simulating absorption of drug at a physiological rate during dissolution studies, especially to predict the performance of formulations of BCS-II drugs. 相似文献
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Xiumei Jiang Xiaowei Zhang Patrick Gray Jiwen Zheng Timothy R. Croley Peter P. Fu 《journal of environmental science and health part c-environmental carcinogenesis & ecotoxicology reviews》2019,37(2):116-131
Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H2O2. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability. 相似文献
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Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation.Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes.Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark).Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC50 value of 13.8?mg/mL on PLA2 from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC50 value of 16.6?mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC50 value of 0.92?mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of??128.96 compared to standard phenidone (?103.61). Thus, the current study validates the application of WS for inflammatory diseases.Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases. 相似文献
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ObjectivesTo assess consumption of dietary and herbal supplements (DHS) among patients in internal medicine departments and determine whether such use is documented in their medical files.Methods267 patients from three internal medicine departments of an academic medical center in Haifa, Israel were assessed prospectively with questionnaires about their DHS use in the month preceding hospitalization. DHS were categorized into vitamins & minerals, herbal supplements and others. Further data was then collected from patients' medical records on socio-demographic and medical characteristics, as well as documentation of DHS use.Results123 patients (50.6 %) used DHS on a daily basis. Most of them (53.7 %) were using more than one DHS. DHS use was more prevalent in older (OR = 1.02 [1.001–1.036], p = 0.034) and educated (OR = 0.482 [0.252-0.923], p = 0.028) patients. Vitamins & minerals were used mainly to enhance vitality and address laboratory abnormalities, whereas herbal supplements were used mainly for gastrointestinal problems (p < 0.001). DHS use was reported to the physicians by 42 % of the patients, mostly at the patients’ initiative [92 (82.1 %), p < 0.001)]. Vitamins and minerals were the most reported category of DHS (94 (57.3 %), p < 0.001). The use of DHS was reported to physicians for 112 DHS (41.8 %) but only 32 DHS (11.9 %) were documented in their medical files. The documentation of vitamins and minerals was significantly higher compared to herbal supplements documentation (29 (17.7 %) & 3 (2.9 %) respectively, P < 0.001).ConclusionsDHS are commonly used by patients hospitalized in the internal medicine departments. Many patients do not report such use to the physicians, and more strikingly, physicians do not document DHS use in patient medical files. This communication gap may have serious medico-legal ramifications due to DHS side effects and DHS interactions with other DHS and with conventional drugs. 相似文献
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Enzyme-Assisted Extraction of Narirutin from Citri Reticulatae Pericarpium and Anti-allergic Asthma Activity
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Xiaolei ShiLina ZhaoLiyan NiuJhao WeiXuwen LiYongri Jin 《Iranian journal of immunology : IJI》2022,19(4):385-394
Background: Asthma is a heterogeneous disorder of the airways related to inflammation; it affects millions of people worldwide. Due to the side effects of inhaled corticosteroids, researchers focused on the therapeutic effects of compounds derived from natural products. Objective: To investigate the therapeutic benefits of Narirutin a valuable flavonoid in Citri Reticulatae Pericarpium for asthma. Methods: Narirutin was extracted using the enzyme-assisted method with the L9 (34) orthogonal array to optimize the temperatures, pH, and reaction time. The mechanism of action of Narirutin was investigated via ELISA, flow cytometry, and Western blot analysis in vivo. Results: Narirutin suppressed inflammatory cell infiltration in the lung tissue and decreased IgE and IgG1 levels in serum in vivo. It can also alleviate interleukin (IL)-4, IL-5, and interferon-γ concentrations in bronchoalveolar lavage fluid in mice. Moreover, it increased the ratio of CD4+/CD8+ T cells. Additionally, Narirutin significantly suppressed p-ERK1/2 and p-JNK expression in the MAPK signaling pathway. Conclusion: Narirutin affects the Th1/Th2 imbalance through the p-ERK and p-JNK suppression in the MAPK signaling pathway. 相似文献