Résumé
OBJECTIVE: To prepare ion-sensitive ophthalmic in situ gel containing bendazac lysine (BDZL-ISG) and preliminarily study its rheological behavior, in vitro drug release, corneal permeation, and pharmacokinetics in rabbit aqueous humor. METHODS: Single factor investigation was carried out to optimize the formulation, taking viscosity and gelling capacity as evaluation indices. Using aqueous solution or eye drops as control, the in vitrorelease of the formulation was evaluated by dialysis membrane method. Then, the corneal permeation experiment of the optimum formulation was carried out with Franz diffusion cell. The pharmacokinetics of BDZL-ISG in rabbit aqueous humor was preliminarily studied by microdialysis. RESULTS: Compared with the control group, the optimum formulation had shear thinning behavior and significant sustained release effect. There was no significant difference in the corneal permeation between the two groups. The results of pharmacokinetic study showed that ρmax (13.25 μg·L-1) and AUC0-t of BZDL-ISG were 2.38 and 2.2 times higher than those of BDZL eye drops respectively, which suggested that the ocular bioavailability of BDZL was greatly enhanced by the optimum in situgel formulation. CONCLUSION: With significant sustained release effect, the ion-sensitive ophthalmic in situ gel will become a promising alterative formulation for bendazac lysine for treatment of cataracts.
Résumé
To investigate the protective effects of bendazac lysine (BDL) on diabetic nephropathy (DN) in vitro and in vivo experiments. METHODS: After rat mesangial cells were cultured in 3 concentrations of BDL for 36 h, the percentages of S phase of cells were determined by flowcytometry; the transforming growth factor β1 (TGF-β1) mRNA level was assayed by reverse transcription PCR; and two main components of extracellular matrix (ECM), collagen Ⅳ and laminin, were determined by radioimmunoassay. Streptozotocin (STZ) induced diabetic rats were administered BDL at doses of 100, 200, 400 mg/kg for 8 weeks. The physical behavior and HbAlC levels of rats were observed. RESULTS: In the presence of high glucose and H2O2, the percentages of S phase of cells were lowered, and TGF-β1 mRNA level, collagen Ⅳ and laminin level were significantly increased. When compared with those in the high glucose group, the percentages of S phase of cells were significantly raised, and the levels of TGF-β1 mRNA, collagen Ⅳ and laminin were statistically decreased. The physical behavior of high BDL treated rats restored to be vibrant, vigorous and weight gaining, and the HbAlC level was significantly reduced. CONCLUSION: BDL has the protective effects against damage caused by DN, and is a potential drug candidate worth further study in preventing and treating DN.
Résumé
Aim To investigate the effects of co-administration of Astragalus Saponin Ⅰ(ASI)and bendazac lysine(BDL)on hypertrophy of cultured rat mesangial cells and its mechanism.Methods The levels of collagen Ⅳ and laminin,the percentages of cells in S phase,the relative quantity of transforming growth factor ?1(TGF-?1) mRNA and indexes of oxidative status were assayed after the cells were incubated in different agents for 36 h.Results The percentage of S phase cells in high glucose group(HG) was greatly decreased while those of vitamin E group(VE) and co-administration groups were increased.The relative quantity of TGF-?1 mRNA and the collagen Ⅳ level in co-administration groups were significantly decreased,and the levels of total anti-oxidative capability(T-AOC),activity of catalase(CAT),GSH-PX,and SOD were greatly increased.Furthermore,the significant differences were found between low ASI(AL)group,low BDL(BL) group and co-administration of low ASI and low BDL(AL+BL) group for TGF-?1 mRNA,T-AOC and GSH-PX;the high ASI group(AH),high BDL group(BH) and co-administration of high ASI and high BDL group(AH+BH) for TGF-?1 mRNA and collagen Ⅳ,respectively. Conclusion Co-administration of ASI and BDL has synergetic effects on regulating TGF-?1,collagen Ⅳ,and radical oxidative stress,therefore,is beneficial to protecting rat mesangial cells against hypertrophy.
Résumé
Objective To evaluate whether the stimulation on eyes of bendazac lysine eyedrops could be reduced by cold storage.Methods Mate design scheme and double-blind clinical trial were performed. 160 healthy eyes was divided into two groups: the test group was given bendazac lysine eyedrops which was stored in refrigerator at 4℃ over night, and the control group was given it which was stored at room temperature.Results ln the control group and the test group, the occuring rate of stimulation was 19.30% and 6.25%. The cases of B、C stimulation degrees were 31 and 10; the average stimulation degrees of each group were 1.21 and 1.07, the scoring change for eye stimulation were 1.57±1.50,0.79±1.40,all respectively. The statistical difference was significant (P＜0.05 or P＜0.01).Conclusion The eye stimulation of bendazac lysine eyedrops can be reduced by cold storage.
Résumé
It has been known that ultraviolet B(UVB) light made an oxidative damage to lens proteins, lipids and nucleic acids to induce lens opacity. The aim of the study was to investigate the effect of bendazac lysine salt (Bendaline) tot the experimental cataract developed by UV irradiation. Forty rats were exposed to 0.1mW/cm2 of UVB radiation in the range 300-320 mm for 24 hours per day. Five control rats were not exposed UVB radiation. During the investigative period, we measured lens opacity with Scheimpflug camera every other week. Rats were divided into 9 groups according to the duration of UV radiation and initial time of bendazac lysine medication. Bendazac lysine was administered orally by 25mg/kg per day for 2 months. The opacities on anterior cortex, nucleus and posterior capsule began to appear 4 months after UVB irradiation. The longer duration of radiation, the more severe opacity of lens was observed, especially at the layers of posterior supranucleus, posterior cortex and posterior capsule and in the opacity area by retroillumination image. After UVB induced cataract was developed, the lens opacity was not changed nevertheless stop the UV irradiation. Lens opacity of bendazac lysine-treated groups was not severer than that of no medication groups. There were less opacities on 4 month irradiated group rather than 6 month irradiated group at the layers of nucleus and posterior cortex and in the opacity area. Anticataract action of bendazac lysine was effective in earlier cataract. In the group of bendazac lysine medication with UVB irradiation on same time, the prophylactic evidence of bendazac lysine was not observed.