氟尿嘧啶与0.9%氯化钠注射液配伍的稳定性研究

目的 考察氟尿嘧啶在0.9％ NaC1注射液中配伍的稳定性,为临床安全、合理用药提供依据.方法 采用高效液相色谱法,考察配伍液中氟尿嘧啶的变化.Scienhome Kromasil C18色谱柱(250 mm×4.6 mm,5μ1);流动相:水(用磷酸二氢钠调节pH 3.5)-甲醇(85∶15);体积流量:1 mL/min;紫外检测波长:266 nm;柱温:室温;进样量:20 μL.将配伍液分别放置在室温、避光和冷藏3个条件下,于0、1、2、4、8、24、48 h观察外观并测定pH值.结果 氟尿嘧啶在5～25 μg/mL线性关系良好(r=0.999 9),平均回收率分别为98.6％、99.00％、99.3％,RSD值分别为0.88％、0.30％、0.45％.配伍液在48 h内无变色、气体、沉淀、浑浊发生,微粒数、pH值无明显变化,氟尿嘧啶的质量分数也无明显变化.结论 氟尿嘧啶与0.9％ NaC1注射液配伍后48 h内稳定.     

A newly synthesized green corrosion inhibitor imidazoline derivative for carbon steel in 7.5% NH4Cl solution

Corrosion and corrosion inhibition behaviors of steel Q-235 were studied in 7.5% NH₄Cl solution with the newly synthesized inhibitor by potentiodynamic polarization together with tests of electrochemical impedance spectroscopy and weight loss measurements in 298–338 K temperature range. The new inhibitor 2-(2-heptadecyl-4, 5-dihydro-1H-imidazole-1-yl) ethanol (HDIE) is synthesized with the help of microwave radiations in solvent free conditions. The results showed that inhibition efficiency above 90% is achievable at 298 K with 0.5 mML^?1 inhibitor concentration. The Adsorption studies revealed that HDIE follows Langmuir model and its adsorption mechanism was mixed-type with predominant effect on anodic half cell. It was seen from the EDS characterization of corroded steel surfaces that the HDIE retarded the corrosion by impeding the chloride attack. Quantum chemical calculations demonstrated that the imidazoline ring and hetero-atoms were active sites. Moreover, an inhibition mechanism was proposed on the basis of the quantum chemical calculations and experimental corrosion studies.     

Dithiocarbamate modified glucose as a novel eco-friendly corrosion inhibitor for copper in sodium chloride media

A novel eco-friendly corrosion inhibitor named dithiocarbamate modified glucose (DTCG) was synthesized from glucose by amination and nucleophilic addition reaction. The anti-corrosion behavior of DTCG for copper in 3 wt% NaCl solution was studied by experimental and theoretical methods. The results show that its maximum inhibitive efficiency can exceed 96% using different technology assessments. DTCG as a mixed-type inhibitor is firmly adsorbed on the copper surface and presents typical chemisorption. DTCG shows significant anti-corrosion performance compared with other glucose-based inhibitors. The DFT calculation results confirms the experimental conclusions.     

Study on corrosion inhibition behavior and adsorption mechanism of novel synthetic surfactants for carbon steel in 1 M HCl solution

The corrosion inhibition behavior and adsorption mechanism of three novel synthetic surfactants in 1 M HCl solution on carbon steel were investigated. The PP results confirmed that all the synthetic surfactants behave as mixed-type inhibitors, while the EIS results validated the existence of a protective layer by the adsorption of inhibitor molecules on the carbon surface. T₃ was observed to offer the highest inhibition efficiency (η_w, 96.28%) at 1 mM by the static weight loss measurements due to two different hydrophobic chains which form a more compact film with the crosswise arrangement. SEM/EDS and XPS results revealed the formation of the surfactants film on the carbon steel surface. Molecular dynamics simulation (MD) was further executed to determine the adsorption mechanism in molecular level insights. In addition, a linear correlation between surface activity (γ) and corrosion inhibition efficiency (η_w) was verified. The adsorption of the prepared surfactants followed the Freundlich isotherm at different concentration ranges. Moreover, the bilayer/multilayer adsorption mechanism was also proposed and confirmed by experimental, adsorption isotherm studies and MD. Hence, both MD simulations and experimental results revealed the analogous inhibition with the order follows: T₃ > T₂ > T₁.     

Experimental and theoretical studies of Ficus religiosa as green corrosion inhibitor for mild steel in 0.5 M H2SO4 solution

Corrosion inhibition analysis and adsorption behaviour of Ficus religiosa fruits extract for mild steel in 0.5 M H₂SO₄ solution has been inquired utilizing scanning electron microscopy (SEM), atomic force microscopy (AFM), gravimetric measurements, electrochemical impendence spectroscopy (EIS), potentiodynamic polarization techniques, Ultraviolet-visible spectroscopy (UV–vis.), Fourier-transform infrared spectroscopy (FT-IR) and quantum chemical calculations. Electrochemical investigation and gravimetric estimations say that the fruits extract of Ficus religiosa shows the most extreme inhibition efficiency of 92.26% at 500 mg/L. The appearance of Myricetin, Serotonin and Campesterol as major phytochemical constituents in the extract of Ficus religiosa, decrease the corrosion rate of mild steel in acidic media. The adsorption of this extract obeys the Langmuir adsorption isotherm. Due to the presence of heteroatoms and aromatic rings in the major components of Ficus religiosa, it can serve as an effective corrosion inhibitor for mild steel corrosion in 0.5 M H₂SO₄.     

Experimental and theoretical assessment of almond gum as an economically and environmentally viable corrosion inhibitor for mild steel in 1 M HCl

Almond gum (AG) was studied as an economically and environmentally viable corrosion inhibitor in 1 M HCl on mild steel (MS). Studies such as gravimetric, NMR, FTIR, EIS, PDP, SEM/EDAX, UV–Visible, DFT and Monte Carlo simulation were performed to assess the potency of AG as a green inhibitor. Gravimetric study was done in the temperature range 30°C–60 °C, I.E increased with increasing concentration and temperature giving significant inhibition efficiency (I.E) of 96.37% at 300 ppm at 60 °C.The adsorption of AG on MS followed Langmuir Adsorption Isotherm. Characterization by NMR and FTIR confirmed the structure of AG. UV–Visible study confirmed the existence of complex [Fe⁺²-AG] on inhibited MS surface. While in 1 M HCl in the presence of AG, MS showed a reduced surface roughness and better surface morphology. Obtained PDP measurements show that AG acts as a mixed type inhibitor but showing predominantly anodic effect while EIS results unveiled the formation of inhibitive layer on the MS surface. I.E calculated from the EIS, PDP showed the same trend as gravimetric. Calculated thermodynamic and activation parameters predicted strong interaction between MS surface and inhibitor. Density functional theory (DFT), condensed Fukui indices (FIs) and Monte Carlo (MC) simulation results further supported the experimental findings.     

Evaluation of the inhibitive effect of Diospyros kaki (Persimmon) leaves extract on St37 steel corrosion in acid medium

A study was conducted to assess the inhibitive effect of Diospyros kaki leaves extract on St37 steel corrosion in 0.1 M HCl solution. Electrochemical (PDP, EIS, DEIS), chemical, and surface morphological screening (SEM, EDS, FTIR) techniques were used in the study. Results show that D. kaki leaves extract is an excellent inhibitor for St37 steel in HCl solution. Maximum inhibition efficiency of 91% was afforded by the highest studied concentration of the extract from PDP measurements. PDP results reveal that the extract components act principally as cathodic type inhibitor suppressing the reduction of hydrogen ions in the cathodic region of the metal. DEIS results show that the studied systems exhibit non-stationary character and the adsorbed extract components were stable particularly at long exposure time. SEM, EDAX, and FTIR results support experimental results that components of D. kaki leaves extract were adsorbed on St37 surface.     

GRGDS-functionalized chitosan nanoparticles as a potential intravenous hemostat for traumatic hemorrhage control in an animal model

Hemostats, which are used for immediate intervention during internal hemorrhage in order to reduce resulting mortality and morbidity, are relatively rare. Here, we describe novel intravenous nanoparticles (CPG-NPs-2000) with chitosan succinate (CSS) as cores, polyethylene glycol (PEG-2000) as spacers and a glycine-arginine-glycine-aspartic acid-serine (GRGDS) peptide as targeted, active hemostatic motifs. CPG-NPs-2000 displayed significant hemostatic efficacy, compared to the saline control, CSS nanoparticles, and tranexamic acid in liver trauma rat models. Further studies have demonstrated that CPG-NPs-2000 are effectively cleared from organs and blood, within 2 and 48?h, respectively. In addition, administration of CPG-NPs-2000 does not affect clotting function under normal physiological conditions, indicating their potential safety in vivo. CPG-NPs-2000 exhibit excellent thermal stability, good solubility, and redistribution ability, in addition to being low cost. These characteristics indicate that CPG-NPs-2000 may have strong potential as effective intravenous hemostats for treating severe internal bleeding.     

Almond waste extract as an efficient organic compound for corrosion inhibition of carbon steel (C38) in HCl solution

In this study, the corrosion inhibition efficiency of almond waste extract on carbon steel (C38) in 1.0 M HCl solution was evaluated using gravimetric analyses, electrochemical tests, and surface characterization. Electrochemical results suggest that almond waste extract significantly enhances the corrosion resistance of C38. To control and understand the stability and adsorption ability of the inhibitor on the steel surface, C38 was tested for various concentrations and temperatures without and with extract inhibitor. The results show that the almond waste exhibits an out-standing inhibition performance in the different experimental conditions. Extract of almond waste acted as a mixed type inhibitor and the adsorption of the corrosion inhibition of C38 was evaluated by Langmuir isotherm model. Adsorption thermodynamic parameters were computed and interpreted. FT-IR analysis and surface morphology affirmed the formation of protective film on C38 surface. The results obtained from experiments revealed that the almond waste extract has a considerable ability to adsorb on C38 surface with high stability of corrosion inhibition at all concentrations were studied here, particularly at high temperatures.     

Superporous hydrogels based on blends of chitosan and polyvinyl alcohol as a carrier for enhanced gastric delivery of resveratrol

Resveratrol exhibits a number of pharmacological properties, notably antioxidant, anti-inflammatory and anti-cancer activities which are beneficial for the treatment of gastric diseases. However, the poor aqueous solubility and rapid metabolism are the important limitations in clinical uses. Superporous hydrogels (SPHs) based on chitosan/PVA blends were developed as a carrier for resveratrol solid dispersion (Res_SD) to increase the solubility and achieve sustained drug release in the stomach. The SPHs were prepared by gas forming method using glyoxal and sodium bicarbonate as cross-linking agent and gas generator, respectively. The solid dispersions of resveratrol with PVP-K30 were prepared by solvent evaporation and incorporated into the superporous hydrogels. All formulations showed rapid absorption of simulated gastric fluid and reached the equilibrium swollen state within a few minutes. The water absorption ratio and mechanical strength of SPHs were predominantly affected by the chitosan content, with maximum values at 1400 % and 375 g/cm², respectively.The Res_SD-loaded SPHs exhibited good floating properties and SEM micrographs revealed a highly interconnected pores structure with size around 150 μm. Resveratrol was efficiently entrapped within the SPHs at levels between 64 and 90 % w/w and efficient drug release was sustained over 12 h dependent on the concentration of chitosan and PVA. The Res_SD-loaded SPHs exhibited slightly less cytotoxic efffect towards AGS cells than pure resveratrol. Furthermore, the formulation showed similar anti-inflammatory activity against RAW 264.7 cells compared with indomethacin.     

Development of starch/chitosan expandable films as a gastroretentive carrier for ginger extract-loaded solid dispersion

Gastroretentive expandable films were developed to provide controlled release of ginger extract (GE) for treatment of gastric diseases. The dosage form consisted of ginger extract solid dispersion (GE-SD) loaded in a starch/chitosan composite film, which was subsequently folded and inserted into a hard gelatin capsule. GE-SD was prepared by solvent evaporation using an optimum weight ratio of 1:1 for GE and PVP K30. Expandable films containing GE-SD were prepared by solvent casting combinations of chitosan and either rice-, glutinous rice - or pregelatinized maize starch with glycerin incorporated as a plasticizer. The optimized film formulation prepared from glutinous rice starch, exhibited tensile strength of 5.4 N/cm² and high expansion in simulated gastric fluid (SGF), resulting in a 2.8-fold increase in area. The films resulted in sustained release of up to 90% of the content of 6-gingerol during 8 h exposure to SGF. Furthermore, the 6-gingerol released from the film displayed dose-dependent cytotoxic activity against AGS human gastric adenocarcinoma cells and anti-inflammatory activity by inhibiting the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells.     

Voltammetric studies of 2-hydroxy-5-[(4-sulfophenyl)azo]benzoic acid as a novel prodrug of 5-aminosalicylic acid

The electrochemical properties of a colon-targeted prodrug of 5-aminosalicylic acid (5-ASA), 2-hydroxy-5-[(4-sulfophenyl)azo]benzoic acid (SPSA), were investigated in aqueous solutions at glassy carbon electrodes using cyclic voltammetry and controlled potential electrolysis. The influence of the pH and experimental time domain on the reaction pathway has been studied. The electrochemical reduction of SPSA is identified as an ECE process always leading to the cleavage of azo bond. In an acidic media SPSA is reduced in a 4e⁻/4H⁺ process yielding 5-ASA and sulfanilic acid. In neutral and weakly basic media SPSA is reduced in 2e⁻/2H⁺ process resulting in the hydrazo intermediate that is stable enough to enable its reoxidation back to SPSA in the time scale of the cyclic voltammetry.     

Voltammetric behaviour of rabeprazole at a glassy carbon electrode and its determination in tablet dosage form

The oxidative behaviour of rabeprazole was studied at a glassy carbon electrode in Britton-Robinson (BR) buffer solutions using cyclic, linear sweep and differential-pulse voltammetry. The oxidation process was shown to be irreversible over the pH range (6.0-11.0) and was diffusion-adsorption controlled. An analytical method was developed for the determination of rabeprazole in BR buffer solution at pH 8.0 as supporting electrolyte. The anodic peak current varied linearly with rabeprazole concentration in the range 1.0 x 10(-6) to 2.0 x 10(-5) M of rabeprazole with a limit of detection of 4.0 x 10(-7) M. Validation parameters, such as sensitivity, accuracy, precision and recovery, were evaluated. The proposed method was applied to the determination of rabeprazole in the tablet dosage form. The results were compared with those obtained by a published high-performance liquid chromatographic method. No difference was found statistically.     

Anti-corrosion investigation of pyrimidine derivatives as green and sustainable corrosion inhibitor for N80 steel in highly corrosive environment: Experimental and AFM/XPS study

Chromeno pyrimidine (CPs) derivatives were synthesized using green approach that involves reaction of multicomponent in one pot using water as solvent. The CPs molecules were tested as potential corrosion inhibitor for N80 steel in 15% hydrochloric acid solution using standard techniques such as weight loss (WT), electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP). CPs are effective corrosion inhibitors giving inhibition efficiency of 96.4% at only 200 mg/L concentration (CP-1). Adsorption of CPs with metal surface involve both physical and chemical interactions. EIS results depicted an increase in charge transfer resistance with increase in concentration of CPs. PDP study suggests mixed mode of CPs inhibition action. The adsorbed inhibitor film was confirmed by AFM and XPS spectra.     

Pterocarpus santalinoides leaves extract as a sustainable and potent inhibitor for low carbon steel in a simulated pickling medium

The crude extract of Pterocarpus santalinoides leaves (PSLE) extracted using water, ethanol, and methanol as the extraction solvent has been studied as inhibitor for low carbon steel in 1 moL/dm³ HCl solution using electrochemical approaches at 25 °C and 60 °C. The results obtained reveal that, PSLE extract has the capacity to effectively suppress the dissolution of the studied substrate. The inhibition performance of PSLE is a function of concentration, temperature, and extraction solvent. Corrosion inhibition is in the order: ethanolic extract > methanolic extract > aqueous extract. With 0.7 g/L PSLE, inhibition efficiency of >90% has been obtained at 60 °C. Based on calculated values of adsorption parameters and UV–vis results, it is proposed that PSLE molecules chemically interacted with the substrate surface. PSLE extract suppressed both the rate of cathodic and anodic reactions according to the PDP results. However, aqueous PSLE extract inhibited anodic corrosion reactions predominantly while ethanolic and methanolic extracts mainly inhibited the cathodic corrosion reactions. Surface characterization studies via SEM, EDAX, and AFM provide experimental evidence to the claim of interaction and presence of PSLE molecules on the studied substrate surface.     

In silico prediction and in vitro and in vivo validation of acaricide fluazuron as a potential inhibitor of FGFR3 and a candidate anticancer drug for bladder carcinoma

Bladder carcinoma (BC) is the ninth most common cause of cancer worldwide. Surgical resection and conventional chemotherapy and radiotherapy will ultimately fail due to tumor recurrence and resistance. Thus, the development of novel treatment is urgently needed. Fibroblast growth factor receptor 3 (FGFR3) is an important and well‐established target for BC treatment. In this study, we utilized the free and open‐source protein–ligand docking software idock to prospectively identify potential inhibitors of FGFR3 from 3,167 worldwide approved small‐molecule drugs using a repositioning strategy. Six high‐scoring compounds were purchased and tested in vitro. Among them, the acaricide drug fluazuron exhibited the highest antiproliferative effect in human BC cell lines RT112 and RT4. We further demonstrated that fluazuron treatment significantly increased the percentage of apoptosis cells, and decreased the phosphorylation level of FGFR3 and its downstream proteins FRS2‐α, AKT, and ERK. We also investigated the anticancer effect of fluazuron in vivo in BALB/C nude mice subcutaneously xenografted with RT112 cells. Our results showed that oral treatment with fluazuron (80 mg/kg) significantly inhibited tumor growth. These results suggested for the first time that fluazuron is a potential inhibitor of FGFR3 and a candidate anticancer drug for the treatment of BC.     

Probing inhibition effect of novel biopolymer based composite for the inhibition of P110 steel corrosion in 15% HCl under dynamic condition

The present work shows the chitosan composite development using Salicylaldehyde (Sali-Cht). The developed composite was used as P110 steel corrosion inhibitor in 15% HCl under dynamic condition at 1500 rpm using electrochemical impedance spectroscopy (EIS), electrochemical frequency modulation (EFM), and potentiodynamic polarization (PDP). The EIS results disclosed that Sali-Cht inhibits corrosion via charge transfer process. The PDP data indicated that Sali-Cht suppresses both the cathodic and anodic corrosion process. The maximum inhibition efficiency of Sali-Cht is 89.23% (400 mg/L). The adsorption of Sali-Cht over the steel surface was confirmed using X-ray photoelectron spectroscopy (XPS). Morphological changes on the steel surface were monitored by scanning electron microscopy (SEM). The thermodynamic parameters such as the adsorption equilibrium constant (K_ads) and the free energy of adsorption (ΔG_ads) were calculated and discussed. Several adsorption isotherms were tested and the experimental data fitted well with the Langmuir adsorption isotherm. Density functional theory (DFT) suggests that protonated forms of Sali-Cht have more adsorption ability than neutral forms. Molecular dynamic simulation (MD) study revealed that protonated form adsorbed flatly over the P110 steel surface, while neutral form adsorbed in a twisted manner.     

Is there a role for dacomitinib,a second-generation irreversible inhibitor of the epidermal-growth factor receptor tyrosine kinase,in advanced non-small cell lung cancer?

ABSTRACT

Introduction

Non-small cell lung cancer (NSCLC) is a highly lethal disease. During the past 20 years, the epidermal growth factor receptor (EGFR) has been a relevant target for anticancer drug-design, and a large family of EGFR tyrosine kinase inhibitors (TKI) were designed, which improved therapeutic outcomes compared to conventional chemotherapy in NSCLC patients with specific EGFR mutations. However, resistance to these inhibitors occurs; therefore, the debate on which inhibitor should be used first is still open. Dacomitinib was approved in 2018 for the first-line treatment of NSCLC with EGFR activating mutations.     

Prediction of a potentially effective dose in humans for BAY 60-5521, a potent inhibitor of cholesteryl ester transfer protein (CETP) by allometric species scaling and combined pharmacodynamic and physiologically-based pharmacokinetic modelling

AIMS

The purpose of this work was to support the prediction of a potentially effective dose for the CETP-inhibitor, BAY 60–5521, in humans.

METHODS

A combination of allometric scaling of the pharmacokinetics of the CETP-inhibitor BAY 60–5521 with pharmacodynamic studies in CETP-transgenic mice and in human plasma with physiologically-based pharmacokinetic (PBPK) modelling was used to support the selection of the first-in-man dose.

RESULTS

The PBPK approach predicts a greater extent of distribution for BAY 60–5521 in humans compared with the allometric scaling method as reflected by a larger predicted volume of distribution and longer elimination half-life. The combined approach led to an estimate of a potentially effective dose for BAY 60–5521 of 51 mg in humans.

CONCLUSION

The approach described in this paper supported the prediction of a potentially effective dose for the CETP-inhibitor BAY 60–5521 in humans. Confirmation of the dose estimate was obtained in a first-in-man study.     

高渗氯化钠溶液复苏失血性休克红细胞内ATP和2.3-DPG水平变化

本文观察了兔失血性休克及应用小剂量7.5％HS(4ml/kg)复苏时RBC内ATP和2,2.3—DPG水平的变化。20只成年健康家兔被随机分为正常血容量输注HS组、休克输注NS复苏组、休克输注HS复苏组三组。结果显示休克后RBC内ATP和2,3—DPG水平显著下降,应用小剂量HS复苏后两项指标均有所回升,在输注后120分钟有显著增高。由于RBC内ATP和2,3—DPG水平是反映RBC能量代谢的主要指标,而RBC代谢状态又可通过影响RBC诸多功能影响组织的氧代谢和休克的转归。因此,笔者认为应用小剂量HS复苏失血性休克的同时RBC能量代谢状态也发生明显改善,这可能是促进HS有效复苏休克的重要因素。