Objective:To develop an etonogestrel (ENG)/ethinyl estradiol (EE) compound vaginal ring with good sustained-release properties, studying its in vitro release assay methodology, and establishing an accelerated release method with good correlation with real-time release methods. Methods:Ethylene-vinyl acetate copolymer (EVA) was used as the matrix to prepare ENG/EE compound vaginal ring by hot melt extrusion method, and an in vitro real-time release assay method and an accelerated release assay method based on shake flask method were established. The in vitro release behavior and release mechanism of ENG/EE compound vaginal ring were investigated, and the correlation between real-time release and accelerated release over time was analyzed. Results:The obtained vaginal ring had a round appearance and a smooth surface, and the drug was slowly released under the optimal real-time release conditions in vitro (release medium: 200 mL of pure water, shaking at 60 r/min in a constant temperature water bath shaker at 37 ℃), and the cumulative release of ENG and EE on the 21st day were 54.39% and 46.80%, respectively. The correlation coefficients of drug release and its mechanism under the optimized in vitro accelerated conditions (release medium: 200 mL of 0.6% sodium dodecyl sulfate aqueous solution, shaking at 60 r/min at 55 ℃) with the results under real-time release conditions were all greater than 0.99. Conclusion:The ENG/EE compound vaginal ring obtained in this study has a significant in vitro sustained-release effect, and the established accelerated release conditions have a good correlation with real-time release conditions, which can provide a useful reference for the quality evaluation research of such vaginal ring products and the formulation of guidelines for in vitro release research methods.

Objective:To develop an etonogestrel (ENG)/ethinyl estradiol (EE) compound vaginal ring with good sustained-release properties, studying its in vitro release assay methodology, and establishing an accelerated release method with good correlation with real-time release methods. Methods:Ethylene-vinyl acetate copolymer (EVA) was used as the matrix to prepare ENG/EE compound vaginal ring by hot melt extrusion method, and an in vitro real-time release assay method and an accelerated release assay method based on shake flask method were established. The in vitro release behavior and release mechanism of ENG/EE compound vaginal ring were investigated, and the correlation between real-time release and accelerated release over time was analyzed. Results:The obtained vaginal ring had a round appearance and a smooth surface, and the drug was slowly released under the optimal real-time release conditions in vitro (release medium: 200 mL of pure water, shaking at 60 r/min in a constant temperature water bath shaker at 37 ℃), and the cumulative release of ENG and EE on the 21st day were 54.39% and 46.80%, respectively. The correlation coefficients of drug release and its mechanism under the optimized in vitro accelerated conditions (release medium: 200 mL of 0.6% sodium dodecyl sulfate aqueous solution, shaking at 60 r/min at 55 ℃) with the results under real-time release conditions were all greater than 0.99. Conclusion:The ENG/EE compound vaginal ring obtained in this study has a significant in vitro sustained-release effect, and the established accelerated release conditions have a good correlation with real-time release conditions, which can provide a useful reference for the quality evaluation research of such vaginal ring products and the formulation of guidelines for in vitro release research methods.

Objective:To explore the feasibility and predictive value of Transit-Time Flow Measurement(TTFM) processed by Fast Fourier Transform(FFT) in evaluating the patency of grafts after coronary artery bypass grafting(CABG).Methods:The TTFM waveforms recorded during the operation of 114 CABG patients in our hospital from January 2015 to February 2017 were processed by FFT, the patients were followed up with CTCA after operation to evaluate the predictive value for graft failure.Results:320 grafts were grafted with the patency rate of 80.3%(257/320). The patency rate of LIMA group was 89.4%(101/113), and SVG group was 75.4%(156/207). H0, H1, H0/H1, and P1 of all grafts, H1and P1 in LIMA group, and H0, H1, P1 in SVG group were significantly different( P<0.05). In logistic regression, decreasing of H0( OR=0.92, 95% CI: 0.90-0.95) and increasing of P1( OR=2.26, 95% CI: 1.64-3.10) in all graft groups increased the risk of graft failure. In the LIMA group, increasing of H1( OR=3.57, 95% CI: 1.79-7.12) and P1( OR=1.53, 95% CI: 1.01-2.33) increased the risk of graft failure. In the SVG group, decreasing of H0( OR=0.83, 95% CI: 0.77-0.89) and H1( OR=0.05, 95% CI: 0.02-0.14), increasing of P1( OR=9.53, 95% CI: 3.04-29.86) increased the risk of graft failure. The ROC curve showed that H0 and P1 had a moderate degree of predictive accuracy in all graft groups. H1 and H0/H1 had a moderate degree of predictive accuracy in LIMA group, and H0 and H1 had a high degree of prediction, P1 had a moderate degree of predictive accuracy in SVG group. Conclusion:TTFM waveform processed by FFT has predictive value for the patency rate of CABG.