Résumé
Objective:To screen new drugs for treatment of phenylalanine hydroxylase deficiency.Methods:From October 2019 to October 2020, virtual drug screening was performed in Center of Genetic Medicine, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University computer according to the characteristics of the binding ability of phenylalanine hydroxylase to drug spatial structure. Ten candidate drugs were screened from the FDA drug library (including 2 697 kinds of active pharmaceutical ingredients). A eukaryotic expression system was used to determine the effects of drugs on the activity of phenylalanine hydroxylase at the molecular level. Drug-sensitive mutants were screened.Results:Among the 10 candidate drugs, neoplasm hydrochloride, fluocinonide acetate and risperidone increased 23% [ t = 18.21, P < 0.001, vs. non-drug-treated phenylalanine hydroxylase group (i.e., only solvent and no drug added to the reaction system)], 21% ( t = 3.44, P < 0.05, vs. non-drug-treated phenylalanine hydroxylase group), 31% ( t = 19.57, P < 0.001, vs. non-drug-treated phenylalanine hydroxylase group) of the activity of phenylalanine hydroxylase. The remaining drugs exhibited weak even inhibitory effects on the activity of phenylalanine hydroxylase. 25% of p.D101N mutant could be activated by risperidone ( t = 15.86, P < 0.001, vs. non-drug-treated p.D101N mutant group). Conclusion:Neoplasm hydrochloride, fluocinonide acetate and risperidone can be used as potential therapeutic drugs for phenylalanine hydroxylase deficiency, and p.D101N mutant can be used as the drug-sensitive mutation site.
Résumé
Objective: To establish a GC method for the determination of resorcinol, borneol, glycerol and DMSO in compound fluocinonide tincture.Methods: The analysis was performed on an HP-INNOWax column (30.0 m×0.32 mm,0.25 μm).The inlet temperature was 280℃ and the detector temperature was 290℃.The split ratio was 10∶1.With nitrogen as the carrier gas, the flow rate was 2.0 ml·min-1.The temperature was as follows: the initial temperature was maintained at 100℃ for 5 min and raised to 240℃ at a rate of 20℃·min-1, and maintaining for 8 min.The flow rate of hydrogen, air and tail blows was 35, 350 and 25 ml·min-1, respectively.Chennai was used as the internal standard.Results: The concentrations of DMSO, resorcinol, borneol and glycerol were within the range of 99.20-793.60 μg·ml-1 (r=0.999 9), 507.25-4 058.00 μg·ml-1 ,respectively(r=0.999 9), 102.20-817.60 μg·ml-1 (r=1.000 0) and 316.20-2529.60 μg·ml-1 (r=1.000 0) with a good linear relationship.The average recovery was 98.58%, 98.34%, 98.19% and 102.29%, and RSDs were 3.80%, 3.93%, 2.87% and 3.65% (n=9), respectively.Conclusion: The method is simple, accurate and reliable, and can be used for the quality control of DMSO, resorcinol, borneol and glycerol in compound fluocinonide tincture.
Résumé
Objective:To establish a method to determine vitamin B 6 and fluocinonide in compound vitamin B 6 gel.Methods:The contents of vitamin B6 and fluocinonide in the gel were determined by HPLC with a Lichrospher CN C 18column (250 mm ×4.6 mm, 5μm).The mobile phase was heptane sulfonate solution (adding 6.8 g potassium phosphate monobasic and 1.0 g heptane sulfonate into 1000 ml water) -methanol –triethylamine (35:65:0.2,adjusting pH to 3.2 with phosphoric acid).The detection wavelength was 238 nm and the column temperature was 25℃.The injection volume was 20 μl.Results: Vitamin B6 had a good linear relationship within the range of 15.0-300.0 μg· ml-1(r=1.000 0), and the average recovery was 99.65% (RSD=0.3, n=9).Fluocinonide had a good linear relationship within the range of 0.4-8.0 μg· ml-1 (r=0.9990), and the average recovery was 99.35% (RSD=0.85, n=9).Conclusion:The method is simple and reproducible, and the result is accurate.The method can be used for the deter-mination of the gel.