Objective:To examine the effect of compound ketotifen eye drops(CKF,containing 0.1% ketotifen and 0.000 5% dexamethasone) on experimental acute allergic conjunctivitis in rats.Methods:27 male Wistar rats were immunized by intraperitoneal injection of egg albumin and were randomized into three groups: CKF,0.1% ketotifen (KF) and 0.000 5% dexamethasone (DM) Rats in each group received the respective eye drops in one eye and vehicle in the other eye 60,45,30,15 min before and 15,30 min after challenge.Immediately before challenge,the rats were injected intravenously with Evans Blue(EB).The challenge was performed by topical instillation of egg albumin,and 60 min later,the animals were killed and the dye was extracted from the eyes.The intensity of EB extravasation was determined by spectrophotometry at 620nm and inhibitory rates were calculated.Results:CKF,KF and DM suppressed EB extravasation significantly.The inhibitory rate was 53.98%±15.57% for CKF,27.91%±28.36% for KF and 11.90%±34.16% for DM.CKF was more effective than both KF and DM on inhibiting dye vascular leakage in the eyes (P＝0.028,0.004,respectively).Conclusion:These data clearly indicate that the compound of ketotifen eye drops has potential as a topical ocular formulation for anti-allergic disease.

Objective　To develop a rapid，sensitive and reliable high-performance gas chromatography to evaluate the fluconazole (FCZ) bioavailability after topically applied FCZ in-situ gelling ophthalmic delivery system to the rabbit eyes.Methods　A megabore capillary column（30m long and inner diameter of 0.530 mm） with a 0.88-μm-thick bonded liquid phase was used.Detector was nitrogen-selective type.Tears adsorbed to the filter paper was directly by methanol with no evaporation stage prior to analysis.Aqueous humors was extracted by ethyl acetate.Results　The duration of each analysis was less 10 min and the minimum detectable concentration was 0.01μg/ml.The assay was linear from 0.1 to 20 μg/ml.The average recoveries from tears and aqueous humors were 99.0% and 94.8%，respectively.Conclusion　This method can be used to determine rabbit tears and aqueous humors levels of fluconazole and was practicable approach for evaluating intraocular pharmacokinetics after topically applied to rabbit eyes.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins