In the present research, we selected Sylysia as a porous material and febuxostat（FBT） as model drug to prepare the FBT SiO2 solid dispersions using a solvent evaporation method. We firstly established an HPLC method...In the present research, we selected Sylysia as a porous material and febuxostat（FBT） as model drug to prepare the FBT SiO2 solid dispersions using a solvent evaporation method. We firstly established an HPLC method for determining FBT in our prepared FBT SiO2 solid dispersions. And then, the characteristics of FBT SiO2 solid dispersions were investigated, including differential scanning calorimetry（DSC）, powder X-ray diffraction（PXRD）, scanning electron microscope（SEM）, particle size and distribution. The solubility and dissolution of FBT SiO2 solid dispersion were also evaluated. The results of DSC and PXRD showed that the FBT existed in an amorphous state in FBT SiO2 solid dispersions. The SEM and particle size results indicated that the shape and average particle size of FBT SiO2 solid dispersions was similar to the Sylysia. The solubility and dissolution of FBT in FBT SiO2 solid dispersions were significantly enhanced compared with the pure FBT. In conclusion, we successfully prepared FBT SiO2 solid dispersions to increase the solubility and dissolution rate of the poorly water-soluble FBT.展开更多
Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout.The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used...Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout.The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment,febuxostat on gut microbiota in gout.16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients,38 gout patients treated with febuxostat,and 26 healthy controls.A restriction of gut microbiota biodiversity was detected in the untreated gout patients,and the alteration was partly restored by febuxostat.Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients.Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism,which was comparatively enhanced in the febuxostat treated gout patients.A classification microbial model obtained a high mean area under the curve up to 0.973.Therefore,gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions.展开更多
Background Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase(XO),may be used in the prevention and management of atrial fibrillation(AF).The purpose of this study was to evaluate the effects of febu...Background Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase(XO),may be used in the prevention and management of atrial fibrillation(AF).The purpose of this study was to evaluate the effects of febuxostat on atrial remodeling in a rabbit model of AF induced by rapid atrial pacing(RAP)and the mechanisms by which it acts.Methods Twenty-four rabbits were randomly divided into four groups:sham-operated group(Group S),RAP group(Group P),RAP with 5 mg/kg per day febuxostat group(Group LFP),and RAP with 10 mg/kg per day febuxostat group(Group HFP).All rabbits except those in Group S were subjected to RAP at 600 beats/min for four weeks.The effects of febuxostat on atrial electrical and structural remodeling,markers of inflammation and oxidative stress,and signaling pathways involved in the left atrium were examined.Results Shortened atrial effective refractory period(AERP),increased AF inducibility,decreased mRNA levels of Cav1.2 and Kv4.3,and left atrial enlargement and dysfunction were observed in Group P,and these changes were suppressed in the groups treated with febuxostat.Prominent atrial fibrosis was observed in Group P,as were increased levels of TGF-β1,Collagen I,andα-SMA and decreased levels of Smad7 and eNOS.Treatment with febuxostat attenuated these differences.Changes in inflammatory and oxidative stress markers induced by RAP were consistent with the protective effects of febuxostat.Conclusions This study is the first to find that febuxostat can inhibit atrial electrical and structural remodeling of AF by suppressing XO and inhibiting the TGF-β1/Smad signaling pathway.展开更多
Quorum sensing is a signal-based communication system in bacteria. It is an attractive target because it regulates the production of virulence factors in Pseudomonas aeruginosa. As a result, interference with quorum s...Quorum sensing is a signal-based communication system in bacteria. It is an attractive target because it regulates the production of virulence factors in Pseudomonas aeruginosa. As a result, interference with quorum sensing could result in inhibition of virulence of Pseudomonas aeruginosa with the merit of lack of selective pressure on growth that leads to development of resistance. This study investigated the anti-quorum sensing and anti-virulence activities of febuxostat in Pseudomonas aeruginosa PAO1 strain. At 1/8 MIC of febuxostat, the production of the quorum-sensing regulated violacein pigment of Chromobacterium violaceum CV026 was significantly reduced. Moreover, it markedly reduced pyocyanin, hemolysin, protease and elastase production. Significant inhibitory activities were also found against biofilm, swimming, twitching and swarming motilities. Molecular docking showed the ability of febuxostat to inhibit quorum sensing by competing with the autoinducers to bind with LasR and RhlR receptors. Febuxostat could bind to both receptors by hydrogen bonding and hydrophobic interaction. From the Molecular docking scores, febuxostat is a very promising quorum sensing inhibitor. Febuxostat could also significantly decrease the level of expression of all QS genes LasI, LasR, RhlI, RhlR, PqsA and PqsR that regulate the production of virulene factors as confirmed by qRT-PCR.展开更多
The objective of the present study was to exhibit the enhanced water-solubility and in vivo oral absorption when febuxostat(FXT) became the salt formation of choline. The formation of the choline salt of febuxostat wa...The objective of the present study was to exhibit the enhanced water-solubility and in vivo oral absorption when febuxostat(FXT) became the salt formation of choline. The formation of the choline salt of febuxostat was confirmed by X-ray powder diffraction, infrared spectroscopy analysis and differential scanning calorimetry. The direct filling method was used to develop a capsule formulation. Cellactose 80 was used as the filler due to its good fluidity, while cross-linked polyvinylpyrrolidone(PVPP) and magnesium stearate(MS) were used as the disintegrant and lubricant, respectively. Then the in vitro release of the formulation was carried out in five different dissolution media including HCl solution(pH 1.2),acetate buffer(pH 4.5), phosphate buffer(pH 6.8 and pH 7.2) and water. Evident improvement of release for choline febuxostat(CXT) was presented in water while the dissolution degree was decreased for CXT in the medium of phosphate buffer(pH 6.8) in comparison with FXT. Furthermore, the pharmacokinetics of CXT was studied in rats using UPLC-MS/MS compared with FXT. The data acquired illustrated that AUC0-24 h of CXT and FXT were22,245.96 ± 7342.92 μg·h/l and 12,249.70 ± 2024.04 μg·h/l, respectively. The relative bioavailability of CXT to FXT was about 181.6% and the P value of AUC0-24 h was less than 0.05. It showed significant difference between the two drugs after oral administration. In conclusion, the water-solubility and oral bioavailability were both improved remarkably for the choline salt of febuxostat and choline salinization was proved an effective way to increase the in vivo absorption for FXT.展开更多
Eco-friendly Ultra-high-performance liquid chromatography (UHPLC) with green aqueous-organic mobile phase was applied for the simultaneous determination of febuxostat (FEB) and diclofenac (DIC) with the composition of...Eco-friendly Ultra-high-performance liquid chromatography (UHPLC) with green aqueous-organic mobile phase was applied for the simultaneous determination of febuxostat (FEB) and diclofenac (DIC) with the composition of water:ethanol (85:15<span> </span>v/v) utilizing phenomenex Kinetex C<sub>18</sub> column (4.6 × 100 mm 2.6 μm), flow rate 1 ml/min and<b><span> </span></b>UV detection at 280 nm<b><span> </span></b>with linear ranges of 0.4 - 4.0 μg/mL and 0.5 - 5.0 μg/mL for FEB and DIC, respectively. The proposed method was also successfully applied to analyze the two drugs in pharmaceutical dosage form and human plasma. The results obtained were validated and statistically analyzed and found to be in accordance with those given by reported methods. Moreover, the greenness of the developed method is assessed using suitable analytical Eco-Scale and GAPI tools<b><span> </span></b>and comparison with the previously published methods have been carried out to indicate the priority of the proposed method. UHPLC is considered eco-friendly method regarding uses of safe solvents, simple, accurate and short time of analysis.展开更多
Objective: the experiment will focus on the implementation of drug therapy for patients with hyperuricemia. The research focuses on the analysis of the application results of febuxostat combined with allopurinol. Meth...Objective: the experiment will focus on the implementation of drug therapy for patients with hyperuricemia. The research focuses on the analysis of the application results of febuxostat combined with allopurinol. Methods: the experiment selected patients with hyperuricemia as the main body of the investigation, and the patients admitted from June 2019 to May 2020 were cut off in the time period. The patients were divided into two groups by using the random number method for comparative study, and the changes of 78 patients' conditions were recorded. The patients in the control group were treated with allopurinol, while those in the observation group were treated with febuxostat combined with allopurinol, and the therapeutic effect was analyzed. Results: from the treatment results, the results of serum uric acid, serum creatinine and urea nitrogen levels in the observation group were better than those in the control group, with significant difference (p < 0.05). At the same time, in the estimation of glomerular filtration rate, the indexes of patients in the observation group after 4 weeks and 12 weeks of treatment are better than those in the control group, and the difference is statistically significant. Conclusion: the combination of febuxostat and allopurinol is effective in the treatment of hyperuricemia, and is helpful to improve the related indicators of blood uric acid. The rehabilitation level of the patients is good and has clinical promotion value.展开更多
Monosodium urate crystals form and deposit in and around the joints due to hyperuricemia,a condition characterized by a prolonged increase in serum urate levels.This leads to tissue supersaturation with urate and resu...Monosodium urate crystals form and deposit in and around the joints due to hyperuricemia,a condition characterized by a prolonged increase in serum urate levels.This leads to tissue supersaturation with urate and results in gout,a prevalent form of inflammatory arthritis.Gout can be effectively managed with febuxostat(FBT),a nonpurine selective xanthine oxidase inhibitor.Despite the efficacy of FBT,its use is limited by poor oral bioavailability and aqueous solubility,which are influenced by its co-administration with food and enzymatic degradation.To address the formulation challenges,topical liposomal formulations can be utilized.These formulations,which leverage the affinity of liposomes for keratin and their ability to penetrate deeper into the skin,offer improved drug absorption.This study aimed to develop a liposomal formulation with soy lecithin and cholesterol using the thin-film hydration method,optimized via the Box-Behnken design.The optimized liposomal formulation was then incorporated into a transdermal gel prepared with Carbopol 934 using the dispersion method.The optimized liposomal formulation demonstrated favorable properties,including a vesicle size of 392.5±11.02 nm,zeta potential of 28±6.13 mV,polydispersity index of 0.127,and high entrapment efficiency as confirmed via transmission electron microscopy.The resulting transdermal gel exhibited the necessary antibacterial activity;excellent stability;in vitro release of 81.33%±1.19%over 7 h;and appropriate pH,viscosity,spreadability,and gel strength.Overall,the liposomal gel formulation represents a highly effective approach for transdermal drug delivery.展开更多
Febuxostat(FXT)is useful in treating hyperuricemia and chronic gout.However,it has limited bioavailability orally due to its low solubility and short half-life.This results in the need for more frequent and larger dos...Febuxostat(FXT)is useful in treating hyperuricemia and chronic gout.However,it has limited bioavailability orally due to its low solubility and short half-life.This results in the need for more frequent and larger doses,increasing the likelihood of adverse effects.Against this background,the current study was established to prepare and optimize an FXT-loaded proniosomal gel using the coacervation-phase separation method.A Quality-by-Design(QbD)methodology was used to ensure the quality of the finished product by assessing how critical process parameters and critical material attributes(CMAs)affected the proniosomal gel’s critical quality attributes.Box-Behnken design was employed to explore the effect of CMAs such as the amount of cholesterol,Span 40,and Span 60 on particle size and entrapment efficiency.The optimized proniosomes had a particle size and percentage entrapment efficiency of 193.7±2.26 nm and 85.3%±0.89%,respectively.Scanning electron microscopy was used to examine the surface morphology of the optimized formulation.The developed formulation was also subjected to in vitro drug release and ex vivo permeation studies,which established the efficiency of the prepared proniosomal gel.Stability studies also established the fact that the prepared formulation is stable to variations in temperature for up to 6 months.展开更多
基金National Natural Science Foundation of China(Grant No.81172992)the National Basic Research Program of China(Grant No.973 Program 2009CB930300)Innovation Team of Ministry of Education(Grant No.BMU20110263)
文摘In the present research, we selected Sylysia as a porous material and febuxostat（FBT） as model drug to prepare the FBT SiO2 solid dispersions using a solvent evaporation method. We firstly established an HPLC method for determining FBT in our prepared FBT SiO2 solid dispersions. And then, the characteristics of FBT SiO2 solid dispersions were investigated, including differential scanning calorimetry（DSC）, powder X-ray diffraction（PXRD）, scanning electron microscope（SEM）, particle size and distribution. The solubility and dissolution of FBT SiO2 solid dispersion were also evaluated. The results of DSC and PXRD showed that the FBT existed in an amorphous state in FBT SiO2 solid dispersions. The SEM and particle size results indicated that the shape and average particle size of FBT SiO2 solid dispersions was similar to the Sylysia. The solubility and dissolution of FBT in FBT SiO2 solid dispersions were significantly enhanced compared with the pure FBT. In conclusion, we successfully prepared FBT SiO2 solid dispersions to increase the solubility and dissolution rate of the poorly water-soluble FBT.
基金the Project of Zhejiang Provincial Department of Education,China(Y202045471)the Project of Wenzhou Science and Technology,China(NO.Y2020205)。
文摘Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout.The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment,febuxostat on gut microbiota in gout.16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients,38 gout patients treated with febuxostat,and 26 healthy controls.A restriction of gut microbiota biodiversity was detected in the untreated gout patients,and the alteration was partly restored by febuxostat.Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients.Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism,which was comparatively enhanced in the febuxostat treated gout patients.A classification microbial model obtained a high mean area under the curve up to 0.973.Therefore,gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions.
基金supported by the Beijing Natural Science Foundation(Z141100002114050)
文摘Background Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase(XO),may be used in the prevention and management of atrial fibrillation(AF).The purpose of this study was to evaluate the effects of febuxostat on atrial remodeling in a rabbit model of AF induced by rapid atrial pacing(RAP)and the mechanisms by which it acts.Methods Twenty-four rabbits were randomly divided into four groups:sham-operated group(Group S),RAP group(Group P),RAP with 5 mg/kg per day febuxostat group(Group LFP),and RAP with 10 mg/kg per day febuxostat group(Group HFP).All rabbits except those in Group S were subjected to RAP at 600 beats/min for four weeks.The effects of febuxostat on atrial electrical and structural remodeling,markers of inflammation and oxidative stress,and signaling pathways involved in the left atrium were examined.Results Shortened atrial effective refractory period(AERP),increased AF inducibility,decreased mRNA levels of Cav1.2 and Kv4.3,and left atrial enlargement and dysfunction were observed in Group P,and these changes were suppressed in the groups treated with febuxostat.Prominent atrial fibrosis was observed in Group P,as were increased levels of TGF-β1,Collagen I,andα-SMA and decreased levels of Smad7 and eNOS.Treatment with febuxostat attenuated these differences.Changes in inflammatory and oxidative stress markers induced by RAP were consistent with the protective effects of febuxostat.Conclusions This study is the first to find that febuxostat can inhibit atrial electrical and structural remodeling of AF by suppressing XO and inhibiting the TGF-β1/Smad signaling pathway.
文摘Quorum sensing is a signal-based communication system in bacteria. It is an attractive target because it regulates the production of virulence factors in Pseudomonas aeruginosa. As a result, interference with quorum sensing could result in inhibition of virulence of Pseudomonas aeruginosa with the merit of lack of selective pressure on growth that leads to development of resistance. This study investigated the anti-quorum sensing and anti-virulence activities of febuxostat in Pseudomonas aeruginosa PAO1 strain. At 1/8 MIC of febuxostat, the production of the quorum-sensing regulated violacein pigment of Chromobacterium violaceum CV026 was significantly reduced. Moreover, it markedly reduced pyocyanin, hemolysin, protease and elastase production. Significant inhibitory activities were also found against biofilm, swimming, twitching and swarming motilities. Molecular docking showed the ability of febuxostat to inhibit quorum sensing by competing with the autoinducers to bind with LasR and RhlR receptors. Febuxostat could bind to both receptors by hydrogen bonding and hydrophobic interaction. From the Molecular docking scores, febuxostat is a very promising quorum sensing inhibitor. Febuxostat could also significantly decrease the level of expression of all QS genes LasI, LasR, RhlI, RhlR, PqsA and PqsR that regulate the production of virulene factors as confirmed by qRT-PCR.
文摘The objective of the present study was to exhibit the enhanced water-solubility and in vivo oral absorption when febuxostat(FXT) became the salt formation of choline. The formation of the choline salt of febuxostat was confirmed by X-ray powder diffraction, infrared spectroscopy analysis and differential scanning calorimetry. The direct filling method was used to develop a capsule formulation. Cellactose 80 was used as the filler due to its good fluidity, while cross-linked polyvinylpyrrolidone(PVPP) and magnesium stearate(MS) were used as the disintegrant and lubricant, respectively. Then the in vitro release of the formulation was carried out in five different dissolution media including HCl solution(pH 1.2),acetate buffer(pH 4.5), phosphate buffer(pH 6.8 and pH 7.2) and water. Evident improvement of release for choline febuxostat(CXT) was presented in water while the dissolution degree was decreased for CXT in the medium of phosphate buffer(pH 6.8) in comparison with FXT. Furthermore, the pharmacokinetics of CXT was studied in rats using UPLC-MS/MS compared with FXT. The data acquired illustrated that AUC0-24 h of CXT and FXT were22,245.96 ± 7342.92 μg·h/l and 12,249.70 ± 2024.04 μg·h/l, respectively. The relative bioavailability of CXT to FXT was about 181.6% and the P value of AUC0-24 h was less than 0.05. It showed significant difference between the two drugs after oral administration. In conclusion, the water-solubility and oral bioavailability were both improved remarkably for the choline salt of febuxostat and choline salinization was proved an effective way to increase the in vivo absorption for FXT.
文摘Eco-friendly Ultra-high-performance liquid chromatography (UHPLC) with green aqueous-organic mobile phase was applied for the simultaneous determination of febuxostat (FEB) and diclofenac (DIC) with the composition of water:ethanol (85:15<span> </span>v/v) utilizing phenomenex Kinetex C<sub>18</sub> column (4.6 × 100 mm 2.6 μm), flow rate 1 ml/min and<b><span> </span></b>UV detection at 280 nm<b><span> </span></b>with linear ranges of 0.4 - 4.0 μg/mL and 0.5 - 5.0 μg/mL for FEB and DIC, respectively. The proposed method was also successfully applied to analyze the two drugs in pharmaceutical dosage form and human plasma. The results obtained were validated and statistically analyzed and found to be in accordance with those given by reported methods. Moreover, the greenness of the developed method is assessed using suitable analytical Eco-Scale and GAPI tools<b><span> </span></b>and comparison with the previously published methods have been carried out to indicate the priority of the proposed method. UHPLC is considered eco-friendly method regarding uses of safe solvents, simple, accurate and short time of analysis.
文摘Objective: the experiment will focus on the implementation of drug therapy for patients with hyperuricemia. The research focuses on the analysis of the application results of febuxostat combined with allopurinol. Methods: the experiment selected patients with hyperuricemia as the main body of the investigation, and the patients admitted from June 2019 to May 2020 were cut off in the time period. The patients were divided into two groups by using the random number method for comparative study, and the changes of 78 patients' conditions were recorded. The patients in the control group were treated with allopurinol, while those in the observation group were treated with febuxostat combined with allopurinol, and the therapeutic effect was analyzed. Results: from the treatment results, the results of serum uric acid, serum creatinine and urea nitrogen levels in the observation group were better than those in the control group, with significant difference (p < 0.05). At the same time, in the estimation of glomerular filtration rate, the indexes of patients in the observation group after 4 weeks and 12 weeks of treatment are better than those in the control group, and the difference is statistically significant. Conclusion: the combination of febuxostat and allopurinol is effective in the treatment of hyperuricemia, and is helpful to improve the related indicators of blood uric acid. The rehabilitation level of the patients is good and has clinical promotion value.
文摘Monosodium urate crystals form and deposit in and around the joints due to hyperuricemia,a condition characterized by a prolonged increase in serum urate levels.This leads to tissue supersaturation with urate and results in gout,a prevalent form of inflammatory arthritis.Gout can be effectively managed with febuxostat(FBT),a nonpurine selective xanthine oxidase inhibitor.Despite the efficacy of FBT,its use is limited by poor oral bioavailability and aqueous solubility,which are influenced by its co-administration with food and enzymatic degradation.To address the formulation challenges,topical liposomal formulations can be utilized.These formulations,which leverage the affinity of liposomes for keratin and their ability to penetrate deeper into the skin,offer improved drug absorption.This study aimed to develop a liposomal formulation with soy lecithin and cholesterol using the thin-film hydration method,optimized via the Box-Behnken design.The optimized liposomal formulation was then incorporated into a transdermal gel prepared with Carbopol 934 using the dispersion method.The optimized liposomal formulation demonstrated favorable properties,including a vesicle size of 392.5±11.02 nm,zeta potential of 28±6.13 mV,polydispersity index of 0.127,and high entrapment efficiency as confirmed via transmission electron microscopy.The resulting transdermal gel exhibited the necessary antibacterial activity;excellent stability;in vitro release of 81.33%±1.19%over 7 h;and appropriate pH,viscosity,spreadability,and gel strength.Overall,the liposomal gel formulation represents a highly effective approach for transdermal drug delivery.
文摘Febuxostat(FXT)is useful in treating hyperuricemia and chronic gout.However,it has limited bioavailability orally due to its low solubility and short half-life.This results in the need for more frequent and larger doses,increasing the likelihood of adverse effects.Against this background,the current study was established to prepare and optimize an FXT-loaded proniosomal gel using the coacervation-phase separation method.A Quality-by-Design(QbD)methodology was used to ensure the quality of the finished product by assessing how critical process parameters and critical material attributes(CMAs)affected the proniosomal gel’s critical quality attributes.Box-Behnken design was employed to explore the effect of CMAs such as the amount of cholesterol,Span 40,and Span 60 on particle size and entrapment efficiency.The optimized proniosomes had a particle size and percentage entrapment efficiency of 193.7±2.26 nm and 85.3%±0.89%,respectively.Scanning electron microscopy was used to examine the surface morphology of the optimized formulation.The developed formulation was also subjected to in vitro drug release and ex vivo permeation studies,which established the efficiency of the prepared proniosomal gel.Stability studies also established the fact that the prepared formulation is stable to variations in temperature for up to 6 months.
