The purpose of this study was to develop and optimize the propranolol once-daily extended release formulations containing HPMC, Microcrystalline cellulose (MCC) and lactose. In vitro studies, the response surface methodology and multiple response optimization utilizing the polynomial equation were used to search for the optimal formulation with specific release rate at different time intervals. The constrained mixture experimental design was used to prepare systematic model formulations, which were composed of three formulation variables: the content of HPMC (X(1)) MCC (X(2)) and lactose (X(3)). The drug release percent at 1.5, 4, 8, 14 and 24 h were the target responses and were restricted to 15-30, 35-55, 55-75, 75-90 and 90-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrix tablets followed non-Fickian diffusion. In the vivo study, the MRT was prolonged for matrix tablets when compared with commercial immediate release tablets. Furthermore, a linear relationship between in vitro dissolution and in vivo absorption was observed in the beagle dogs. 相似文献
Notexin, a presynaptic phospholipase A2 (PLA2) neurotoxin isolated from Notechis scutatus scutatus venom, was inactivated by arginine-specific reagents, phenylglyoxal and 1,2-cyclohexanedione. Kinetic analyses of the modification reaction revealed that the inactivation of notexin followed pseudo-first order kinetics and the loss of PLA2 activity was correlated with the incorporation of one molecule of modification reagent per toxin molecule. However, the results of amino acid analysis and sequence determination revealed that two arginine residues at positions 43 and 79 of notexin were modified simultaneously. Modification of the arginine residues was accompanied with a decrease in the ability to inhibit the indirectly evoked contraction of chick biventer cervicis muscle and bind with synaptic membranes. The secondary structure of the toxin molecule did not significantly change after modification with phenylglyoxal as revealed by the CD spectra. The modified derivative retained its affinity for Ca2+, indicating that the modified arginine residues did not participate in Ca2+ -binding. Together with the notion that Arg-43 and Arg-79 of notexin are located in the proximity of its catalytic site and toxic site, respectively, our results suggest that modification of Arg-43 and Arg-79 should differently contribute to the observed decrease in the PLA2 activity and neurotoxic effect of notexin. 相似文献
AIM: To evaluate the efficacy and safety of intravitreal injection of conbercept in patients with neovascular age-related macular degeneration (AMD).
METHODS: Retrospective review of 66 eyes of 63 patients with neovascular AMD. All patients received 0.5 mg intravitreal injections of conbercept monthly for 3 consecutive months, and then pro re nata treatment was performed. The changes of best-corrected visual acuity (BCVA) and central macular thickness (CMT) were observed before and after treatments. Minimum follow-up time was 12mo. SPSS 22.0 statistical software was used for statistical analysis.
RESULTS: The mean BCVA and CMT of 66 eyes (63 patients) were 1.11±0.60, 533.20±219.95 μm at baseline, and were 0.68±0.38, 310.28±125.60 μm at 3mo. No subjects were lost during the first three months, the improvements were all significantly (P<0.05). During the whole follow-up time of 12mo, 15 subjects (18 eyes) were lost. The mean BCVA and CMT of the rest 48 eyes with the follow-up time at least 1y were 0.83±0.46 and 547.59±196.77 μm at baseline, after 3mo and 12mo of conbercept injections became 0.55±0.41, 318.24±141.29 μm and 0.55±0.51, 333.87±173.25 μm. The differences were significant (P<0.05). No serious complications were observed.
CONCLUSION: Intravitreal injection of conbercept appears to significantly improve visual acuity and anatomical outcomes in patients with neovascular AMD, no serious adverse reactions and complications are observed. 相似文献
AIM: To investigate the incidence of abrupt visual loss and its associated factors, during anti-vascular endothelial growth factor (VEGF) treatment for type 3 neovascularization.
METHODS: This retrospective study included 137 eyes that were newly diagnosed with type 3 neovascularization. All eyes were treated with anti-VEGF therapy. Abrupt visual loss was defined as loss of 5 or more lines in best-corrected visual acuity (BCVA) in comparison to the previous visit. The incidence and timing of abrupt visual loss as well as the factors associated with it, were determined. In addition, the BCVA at the final follow-up was compared between the eyes with and those without abrupt visual loss.
RESULTS: The mean follow-up period was 42.4±18.9mo after diagnosis, and abrupt visual loss was noted in 22 eyes (16.1%) at a mean of 19.6±13.9mo. Abrupt visual loss was found to be associated with subretinal hemorrhage in 11 eyes (50.0%), development of or increase in the height of pigment epithelial detachment with fluid in 8 eyes (36.4%), and tears in the retinal pigment epithelium in 3 eyes (13.6%). The logarithm of minimum angle of resolution (logMAR) mean BCVA at the final follow-up was 2.07±0.67 (Snellen equivalents: 20/2349) and 1.00±0.55 (20/200) in eyes with and without abrupt visual loss, respectively. BCVA was significantly worse in the eyes with abrupt visual loss (P<0.001).
CONCLUSION: Abrupt visual loss is noted in 16.1% of patients with type 3 neovascularization and is associated with poor visual outcome. Additional studies are needed to determine how abrupt visual loss can be prevented. 相似文献