ABSTRACT
This paper describes a study exploring the interaction between gomizine D and α-glucosidase. The inhibitory activity of α-glucosidase by gomizine D was determined using PNPG as substrates Gomizine D gave the IC₅₀ value of 0.59 mmol•L⁻¹, which was higher than that of acarbose (1.95 mmol•L⁻¹). Gomizine D was a reversible and non-competitiveα-glucosidase inhibitor with an inhibition constant Ki=4.026 g•L⁻¹. The binding mode between gomizine D and α-glucosidase was analyzed by AutoDock Vina molecular docking software. The lowest energy of Gomizine D binding to α-glucosidase was -7.7 kcal•mol⁻¹, which was lower than that of acarbose (-6.6 kcal•mol⁻¹). After binding with gomizine D, UV spectroscopy analysis displayed that the microenvironment of aromatic residue in the secondary structure of α-glucosidase was changed, and the polarity of protein was reduced.
ABSTRACT
Background The clinical efficacy and safety of mouse nerve growth factor(NGF) for injection have been evaluated by Ⅰ,Ⅱ,Ⅲ stage of clinical trials.But as a clinical drug,its adverse effects for special population should been further studied.Objective This clinical trial was to observe and assess the safety and tolerability of mouse NGF for injection during the application in juvenile and elder patients with optic nerve damage.Methods A multicenter non-randomized controlled trial for the safety evaluation of mouse NGF injection solution was performed in 100 eye centers in China.This study protocol was approved by the Ethic Committee of each drug research center,and written informed consent was obtained from the subject,legal mandatary and guardian prior to this study.Total 2046 patients who met the included criteria of optical nerve damage were enrolled.The patients were divided into the juvenile group(90 cases,＜ 18 years),youth-middle-age group (1868 cases,1 8-75 years) and older group(88 cases,＞75 years).Mouse NGF(30 μg)was intranuscularly injected once per day for 21 days in all the patients.Systolic and diastolic blood pressure,heart rate,intraocular pressure (lOP),laboratory examinations of blood and urine,blood biochemical indexes were recorded before and after injection.All adverse events were evaluated after administration of drug.Results There were 189 (189/2046,9.23％)dropped out cases,including 184 lost cases after 3 weeks of treatment and 5 withdrew cases from adverse responses of drug,with a shedding rate ＜10％ in each group.Total 1857 individuals finished this trial.No significant differences were found in the IOP,heart rate and blood pressure between before and after admninistration of grug in the juvenile group,youth-middle-age group and older group (P＞0.05).The incidence rate of the adverse response in the juvenile group,youth-middle-age group and older group was 57.78％,68.18％,60.01％ respectively,and the primary local adverse events were pain(48.89％),redness and swelling(59.09％),duration(54.49％),without significant difference in the rate of local adverse events among the three groups(X2 =2.302,P =0.324).The abnormal rates of laboratory results of blood and urine were not significantly different among the three groups(all at P＞0.05).The percentage of impaired fasting glucose was 7.46％,23.73％and 7.79％ in the juvenile group,youth-middle-age group and older group,respectively,and the percentage in the older group was higher than that in the juvenile group and the youth-middle-age group (x2 =8.685,P =0.005 ;x2 =27.720,P =0.000).Conclusions Injection of mouse NGF is well tolerated in juvenile and elder patients over the age of 75 years.