A stability indicating LC method was developed for the simultaneous determination of Amlodipine and Benazepril capsules in pharmaceutical dosage form. Efficient chromatographic separation was achieved on Symmetry C18 ...A stability indicating LC method was developed for the simultaneous determination of Amlodipine and Benazepril capsules in pharmaceutical dosage form. Efficient chromatographic separation was achieved on Symmetry C18 stationary phase with simple combination of amobile phase containing 750 mL of DI Water, 250 mL of Acetonitrile and 2 mL of Octylamine into suitable container with adjusted pH to 2.50 ± 0.05 with the aid of Ortho phosphoric acid delivered in an isocratic mode and quantification was carried out using UV detection at 240 nm at a flow rate of 1.0 mL·min-1 with an injection volume of 20 μl and ambient column temperature. This method is capable to detect both the drug components of Amlodipine and Benazepril in presence of their degradation products (Amlodipine Imp-A and Benazepril Impurity-C) with a detection level of 0.05%. Amlodipine/Benazepril in their combination drug product were exposed to thermal, photolytic, hydrolytic and oxidative stress conditions, and the samples were analysed. Peak homogeneity data of Amlodipine and Benazeprilis were obtained using PDA detector, in the stressed sample chromatograms, demonstrating the specificity. The method shows excellent linearity over a range of 0.05%-2.0% for Amlodipine, Amlodipine Impurity-A and 0.05%-5.0% for Benazepril and Benazepril Impurity-C. The correlation coefficient for Amlodipine and Benazepril is 1. The relative standard deviation was always less than 2%. The proposed method was found to be suitable and accurate for quantitative determination and the stability study of Amlodipine and Benazepril in pharmaceutical preparations. The developed HPLC method was validated with respect to linearity & range, accuracy, precision and robustness.展开更多
Objective:To explore the protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms.Methods:A total of 50...Objective:To explore the protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms.Methods:A total of 50 patients with early diabetic nephropathy treated in our hospital between May 2012 and January 2016 were collected, and according to the random number table, the patients were divided into observation group (n=25) and control group (n=25). On the basis of conventional treatment, control group of patients received benazepril therapy, observation group of patients received calcium dobesilate combined with benazepril therapy, and the treatment lasted for 3 months. Before and after treatment, automatic biochemical analyzer was used to detect the levels of renal injury indexes in peripheral blood, RIA method was used to detect the levels of renal injury indexes in urine, ELISA method was used to detect the levels of renal fibrosis indexes and Western-blot method was used to detect the protein expression of TGF-β1/BMP-7 and Smad signaling pathway molecules in renal tissue. Results: Before treatment, differences in renal injury index levels, renal fibrosis index levels and signaling pathway molecule protein expression were not statistically significant between two groups of patients. After treatment, BUN, SCr andβ-TP levels in the peripheral blood as well as KIM-1 level in urine of observation group were lower than those of control group;renal fibrosis indexes TGF-β1, CTGF, TIMP-1, LN and HA levels in serum of observation group were lower than those of control group;TGF-β1 and Smad2/3 protein expression in renal tissue of observation group were lower than those of control group while Smad7 and BMP-7 protein expression were higher than those of control group.Conclusion: Calcium dobesilate combined with benazepril therapy can reduce the renal injury and inhibit the fibrosis process in patients with early diabetic nephropathy, and it achieves the above effect by regulating the TGF-β1/BMP-7 and Smad signaling pathway function.展开更多
Objective To explore the changes of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiogenesis, and the effects of bFGF, angiotensin converting enzyme inhibiter(ACEI) benazepril ...Objective To explore the changes of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiogenesis, and the effects of bFGF, angiotensin converting enzyme inhibiter(ACEI) benazepril on the angiogenesis in acute myocardial infarction (AMI) model of rabbits, and to provide a probable evidence for the treatment of AMI. Methods AMI model was established by ligating anterior descending branch of coronary artery of Japan-Sino hybridization white rabbits. The postoperative rabbits were randomly divided into 6 groups and each group was treated with different drugs. Groups 1 and 2 were treated with normal saline (NS) for 28 and 14 days (d), group 3 and 4 with bFGF for 28 and 14 d, groups 5 with benazepril for 14 d, and group 6 with benazepril and bFGF for 14 d respectively. The rabbits were killed on the 14th or 28th d and their hearts were excised, sectioned and stained with HE, Masson trichrome to observe VEGF, bFGF and CD34 under a microscope, which were quantified with a computer-assisted morphometry. Results Compared with group 1, the granulation tissue of infarction zone (IZ) in group 2 freshened up, and the capillary density (CD) in IZ was increased (P=0.002). The CD in the IZ as well as VEGF and bFGF in groups 3 and 4 were increased respectively (P=0.011-0.037). In group 5 the changes of VEGF and bFGF were not found in the IZ and the border zone (BZ) while CD was significantly increased (35.4% and 25.6%, P=0.036 and 0.037). Compared with group 2, the CD in the IZ and BZ of group 6 was significantly increased (63.4% and 44.3% P=0.007 and 0.007), meanwhile VEGF and bFGF were increased. Compared with group 5, only VEGF was increased. Conclusion Intravenous bFGF may increase VEGF and bFGF significantly, thus promoting the angiogenesis in the IZ and BZ in cardiac infarction as VEGF and bFGF are the potent angiogenic growth factors. Benazepril may promote angiogenesis in the IZ and BZ in cardiac infarction, but its mechanism is irrelative to the expression of VEGF and bFGF. The combination of benazepril and bFGF may promote, to some extent, the expression of VEGF and bFGF, but their effect on angiogenesis has not been found.展开更多
Summary: The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-relate...Summary: The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.展开更多
This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system (RAAS) and clock genes in the kidney. The male Wistar rat model...This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system (RAAS) and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy (STNx) were established. Animals were randomly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril group (MB) and evening benazepril group (EB). Benazepril was intragastrically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angiotensin Ⅱ (AngⅡ) and aldosterone (Ald) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmal1, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no significant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Ald and RA content of a day between the MB group and EB group. The expression peak of bmal1 mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.展开更多
The present work relates to a new synthesis process for the preparation of 3-[(1-ethoxycarbonyl-3-phenylpropyl)-amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetate tert butyl ester(EPTAB),the precursor of benaz...The present work relates to a new synthesis process for the preparation of 3-[(1-ethoxycarbonyl-3-phenylpropyl)-amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetate tert butyl ester(EPTAB),the precursor of benazepril HCl.The reaction conditions were optimized.The diastereomeric products were separated by flash column chromatography.The structures of the products were characterized with IR and NMR.展开更多
文摘A stability indicating LC method was developed for the simultaneous determination of Amlodipine and Benazepril capsules in pharmaceutical dosage form. Efficient chromatographic separation was achieved on Symmetry C18 stationary phase with simple combination of amobile phase containing 750 mL of DI Water, 250 mL of Acetonitrile and 2 mL of Octylamine into suitable container with adjusted pH to 2.50 ± 0.05 with the aid of Ortho phosphoric acid delivered in an isocratic mode and quantification was carried out using UV detection at 240 nm at a flow rate of 1.0 mL·min-1 with an injection volume of 20 μl and ambient column temperature. This method is capable to detect both the drug components of Amlodipine and Benazepril in presence of their degradation products (Amlodipine Imp-A and Benazepril Impurity-C) with a detection level of 0.05%. Amlodipine/Benazepril in their combination drug product were exposed to thermal, photolytic, hydrolytic and oxidative stress conditions, and the samples were analysed. Peak homogeneity data of Amlodipine and Benazeprilis were obtained using PDA detector, in the stressed sample chromatograms, demonstrating the specificity. The method shows excellent linearity over a range of 0.05%-2.0% for Amlodipine, Amlodipine Impurity-A and 0.05%-5.0% for Benazepril and Benazepril Impurity-C. The correlation coefficient for Amlodipine and Benazepril is 1. The relative standard deviation was always less than 2%. The proposed method was found to be suitable and accurate for quantitative determination and the stability study of Amlodipine and Benazepril in pharmaceutical preparations. The developed HPLC method was validated with respect to linearity & range, accuracy, precision and robustness.
文摘Objective:To explore the protective effect of calcium dobesilate combined with benazepril therapy on renal injury in patients with early diabetic nephropathy and the possible molecular mechanisms.Methods:A total of 50 patients with early diabetic nephropathy treated in our hospital between May 2012 and January 2016 were collected, and according to the random number table, the patients were divided into observation group (n=25) and control group (n=25). On the basis of conventional treatment, control group of patients received benazepril therapy, observation group of patients received calcium dobesilate combined with benazepril therapy, and the treatment lasted for 3 months. Before and after treatment, automatic biochemical analyzer was used to detect the levels of renal injury indexes in peripheral blood, RIA method was used to detect the levels of renal injury indexes in urine, ELISA method was used to detect the levels of renal fibrosis indexes and Western-blot method was used to detect the protein expression of TGF-β1/BMP-7 and Smad signaling pathway molecules in renal tissue. Results: Before treatment, differences in renal injury index levels, renal fibrosis index levels and signaling pathway molecule protein expression were not statistically significant between two groups of patients. After treatment, BUN, SCr andβ-TP levels in the peripheral blood as well as KIM-1 level in urine of observation group were lower than those of control group;renal fibrosis indexes TGF-β1, CTGF, TIMP-1, LN and HA levels in serum of observation group were lower than those of control group;TGF-β1 and Smad2/3 protein expression in renal tissue of observation group were lower than those of control group while Smad7 and BMP-7 protein expression were higher than those of control group.Conclusion: Calcium dobesilate combined with benazepril therapy can reduce the renal injury and inhibit the fibrosis process in patients with early diabetic nephropathy, and it achieves the above effect by regulating the TGF-β1/BMP-7 and Smad signaling pathway function.
文摘Objective To explore the changes of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiogenesis, and the effects of bFGF, angiotensin converting enzyme inhibiter(ACEI) benazepril on the angiogenesis in acute myocardial infarction (AMI) model of rabbits, and to provide a probable evidence for the treatment of AMI. Methods AMI model was established by ligating anterior descending branch of coronary artery of Japan-Sino hybridization white rabbits. The postoperative rabbits were randomly divided into 6 groups and each group was treated with different drugs. Groups 1 and 2 were treated with normal saline (NS) for 28 and 14 days (d), group 3 and 4 with bFGF for 28 and 14 d, groups 5 with benazepril for 14 d, and group 6 with benazepril and bFGF for 14 d respectively. The rabbits were killed on the 14th or 28th d and their hearts were excised, sectioned and stained with HE, Masson trichrome to observe VEGF, bFGF and CD34 under a microscope, which were quantified with a computer-assisted morphometry. Results Compared with group 1, the granulation tissue of infarction zone (IZ) in group 2 freshened up, and the capillary density (CD) in IZ was increased (P=0.002). The CD in the IZ as well as VEGF and bFGF in groups 3 and 4 were increased respectively (P=0.011-0.037). In group 5 the changes of VEGF and bFGF were not found in the IZ and the border zone (BZ) while CD was significantly increased (35.4% and 25.6%, P=0.036 and 0.037). Compared with group 2, the CD in the IZ and BZ of group 6 was significantly increased (63.4% and 44.3% P=0.007 and 0.007), meanwhile VEGF and bFGF were increased. Compared with group 5, only VEGF was increased. Conclusion Intravenous bFGF may increase VEGF and bFGF significantly, thus promoting the angiogenesis in the IZ and BZ in cardiac infarction as VEGF and bFGF are the potent angiogenic growth factors. Benazepril may promote angiogenesis in the IZ and BZ in cardiac infarction, but its mechanism is irrelative to the expression of VEGF and bFGF. The combination of benazepril and bFGF may promote, to some extent, the expression of VEGF and bFGF, but their effect on angiogenesis has not been found.
文摘Summary: The effects of the combined use of angiotensin converting enzyme inhibitor (ACEI) benazepril and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) valsartan on apoptosis and the expression of apoptosis-related proteins Fas and FasL in the kidney of rats with adriamycin-induced nephritic glomerulosclerosis was investigated. Uninephrectomy and the injection of adriamycin induced the rat model of glomerulosclerosis. Benazepril (6 mg/kg), valsantan (20 mg/kg), or benazepril (3 mg/kg) plus valsantan (20 mg/kg) was respectively delivered daily by gavage to the rats in three treatment groups for 12 weeks. Apoptosis was examined by means of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Immunohistochemistry was adopted to detect the expression of Fas and FasL. Software of pathological analysis quantitated the levels of Fas and FasL. The results showed that as compared with those in the control group, the kidneys in the model group had more severe glomerulosclerosis, much more apoptotic cells and higher levels of expression of Fas and FasL. The degree of glomerulosclerosis, the number of apoptotic cells and the levels of expression of Fas and FasL were reduced by benazepril and valsartan. The combined use of benazepril and valsartan had the best therapeutic effect. It was concluded that benazepril and valsartan could suppress the excessive apoptosis of kidney cells by lowering the expression of the apoptosis-related proteins Fas and FasL, so as to postpone the process of glomerulosclerosis. The combined use of benazepril and valsartan has better therapeutic effect.
基金supported by grants from the Department of Public Health of Hubei Province of China (No. 2012Z-B08)the Health Bureau of Wuhan City of China (No. WX12C10)
文摘This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system (RAAS) and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy (STNx) were established. Animals were randomly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril group (MB) and evening benazepril group (EB). Benazepril was intragastrically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angiotensin Ⅱ (AngⅡ) and aldosterone (Ald) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmal1, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no significant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Ald and RA content of a day between the MB group and EB group. The expression peak of bmal1 mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.
文摘The present work relates to a new synthesis process for the preparation of 3-[(1-ethoxycarbonyl-3-phenylpropyl)-amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetate tert butyl ester(EPTAB),the precursor of benazepril HCl.The reaction conditions were optimized.The diastereomeric products were separated by flash column chromatography.The structures of the products were characterized with IR and NMR.
