ABSTRACT
Objective The inclusion complex of vincamine (VIN) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared and characterized. Molecular simulation method was used to study the formation mechanism of inclusion complex. Methods The inclusion complex of VIN/HP-β-CD was prepared by saturated solution. The preparation technology of VIN/HP-β-CD inclusion complex was optimized by orthogonal design, and taking the drug-loading of the inclusion compound as the index. The stability constant of inclusion complex between VIN and HP-β-CD was studied by UV-Vis spectrometry titration, and the inclusion ratio was determined by Job plots method. The VIN/HP-β-CD inclusion complex was characterized by scanning electron microscope (SEM), X-ray powder diffractometry (XRD), infrared spectroscopy (IR), thermal analysis techniques (TG and DSC), and nuclear magnetic resonance (1H, 2D NMR). The water solubility of the VIN/HP-β-CD inclusion complex was measured and the stability test was conducted in the simulated human gastric juice and intestinal fluid environment. Molecular docking and molecular dynamics were used to study the forming mechanism of supramolecular system of VIN/HP-β-CD. Results Using saturated solution method, the optimum conditions of inclusion were: 1:1 for molar ratio of VIN and HP-β-CD, 40 ℃ for inclusion temperature, 7 h for inclusion time and volume ratio of methanol to water (1:6) as solvent; Job curve and UV-vis spectroscopy showed that inclusion ratio of host-guest inclusion complexes was 1:1; After VIN formed inclusion complexes with HP-β-CD, its solubility increased from 0.04 mg/mL to 16.5 mg/mL, and the thermal decomposition temperature of VIN increased from 240.5 ℃ to 306.1 ℃. 1H-NMR and NOESY spectra indicated that the inclusion complex was formed by the a-ring of VIN entering from the large end of HP-β-CD. Quantum chemical calculation and molecular docking indicated that the optimal inclusion mode was consistent with the results of NMR studies. Molecular dynamics studies showed that VIN can penetrate into the hydrophobic cavity of HP-β-CD in water environment, and the interaction between host and guest was strengthened. The space size of host-guest matched better. Conclusion The solubility and thermal stability were significantly improved after the formation of inclusion complex with VIN and HP-β-CD. Hydrophobicity, hydrogen bonding, and van der Waals forces were the main driving forces for inclusion complex formation.
ABSTRACT
AIM: To observe the clinical efficacy and safety of vincamine sustained release capsules on non- arteritic anterior ischemic optic neuropathy ( NAION) . · METHODS: Patients who were diagnosed with monocular onset NAION in acute stage from January to September 2015 were divided into two groups. Routine treatment such as steroid pulse therapy and neurotrophic treatment were given to all the patients. Vincamine was added to the treatment group patients with 30mg twice a day for 3mo. The best corrected visual acuity ( BCVA), mean deviation ( MD) of visual field, retinal nerve fiber layer ( RNFL ) , ganglion cell complex ( GCC ) , pattern visual evoked potential ( PVEP ) and OCT results were analyzed before and after the treatment. ·RESULTS:Totally 42 eyes of 42 patients were enrolled in our study. There were 27 patients in the treatment group, aged from 33 to 79 years old, the average value was 55. 55± 11. 83 years old. The control group has 15 patients, aged from 40 to 70 years old, the average value was 55. 71 ± 10. 06 years old. There were no statistical differences between the two groups in the baseline. After 3mo of the treatment, MD value of the two groups were lower compared with the baseline, the difference was statistically significant in the treatment and control group respectively (t= 2. 342, 2. 692; P = 0. 027, 0. 041). The difference of PVEP amplitude and potential of the two groups before and after the treatment were not statistically significant. The thickness of retinal nerve fiber layer and the ganglion cell complex were all lower than the baseline, and the difference was statistically significant (P<0. 001). The treatment of the two groups were both effective, the treatment group has better treatment effect than the control group. Adverse events related to the treatment of vincamine had not been found. ·CONCLUSION:Vincamine is helpful in the treatment of non-arteritic anterior ischemic optic neuropathy.