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OBJECTIVE:To screen the optimal micronization technology of Alitretinoin crude drug. METHODS:Using characteristic value of particle size distribution [d(0.9)] and the content of impurity A of crude drug after crushed as indexes, crushing method(universal pulverizer,ball crusher,airslide disintegrating mill),crushing gas source(compressed air,high pressure nitrogen)and crushing pressure(0.2,0.4,0.6 MPa)of Alitretinoin crude drug were screened,and validation test was also conducted. RESULTS:The optimal technology was as follows as airslide disintegrating mill,high pressure nitrogen as gas source,at 0.4 MPa.In validation test,particle sizes for 3 batches of crude drug after crushed were 8.57,8.55,8.54 μm(<10 μm, RSD=0.15%,n=3). The content of impurity A was not increased compared with before crushed(0.07%). CONCLUSIONS:Screened micronization technology of Alitretinoin crude drug is feasible and stable in quality.
RESUMO
BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks provided a virological response comparable to that of TDF and entecavir (ETV) combination therapy in patients infected with ETV-resistant hepatitis B virus (HBV). Little long-term data in routine clinical practice are available regarding the optimal treatment of patients with ETV-resistant HBV. METHODS: We investigated the long-term antiviral efficacy of combination therapy of TDF+lamivudine (LAM) or TDF+ETV compared to that of TDF monotherapy in 73 patients with resistance to both LAM and ETV. RESULTS: Patients were treated with TDF monotherapy (n=12), TDF+LAM (n=19), or TDF+ETV (n=42) for more than 6 months. The median duration of TDF-based rescue therapy was 37 months. Virologic response (VR) was found in 63 patients (86.3%). The rates of VR among the three groups (TDF monotherapy, TDF+LAM, and TDF+ETV) were not statistically different (log-rank P=0.200) at 12 months (59.3%, 78.9%, and 51.8%, respectively) or at 24 months (88.4%, 94.7%, and 84.2%). In addition, treatment efficacy of TDF-based combination or TDF monotherapy was not statistically different with ETV-resistant strains or exposure to other antiviral agents. In multivariate analysis, only lower baseline HBV DNA level was an independent predictor for VR (hazard ratio, 0.723; 95% confidence interval, 0.627-0.834; P<0.001). CONCLUSIONS: TDF monotherapy was as effective as combination therapy of TDF+LAM or TDF+ETV in maintaining long-term viral suppression in chronic hepatitis B patients with resistance to both LAM and ETV. HBV DNA level at the start of TDF rescue therapy was the only independent predictor of subsequent VR.