The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the ...The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the combination therapy with these two synergistic drugs at low doses through a suitable form of administration could provide optimal therapeutic benefit, we further evaluated the effects of a 42 d period of anti-hypertensive treatment in spontaneously hypertensive rats. Rats were divided into the following five groups： control （blank patch）, bisoprolol fumarate tablets （BP-FT, 20.0 mg/kg, i.g.）, bisoprolol transdermal patch （BP-TP, 20.0 mg/kg）, isosorbide dinitrate transdermal patch （ISDN-TP, 20.0 mg/kg）, and the combination of BP and ISDN in a transdermal patch at low doses （8 and 12 mg/kg, respectively）. The effects of treatment were evaluated via biochemical indicators related to cardiovascular protection, structure and function. The combination therapy had synergistic anti-hypertensive effects and significantly reduced blood pressure with the benefit of controlling blood pressure variability compared to BP-FT and BP-TP. The combined treatment also reduced heart rate as well as BP-FT and BP-TP, while ISDN-TP had no evident effects on blood pressure, heart rate, and cardiovascular protection. Combination therapy was superior to BP-TP and BP-FT at increasing blood atrial natriuretic peptide and nitric oxide, while also reducing cardiac hydroxyproline and endothelin-1 with no difference in blood endothelin-1 and cardiac malondialdehyde levels. Cardiovascular remodeling differed among the groups, with the combination therapy reducing cardiac hypertrophy and the aortic media/lumen ratio. The consequential improvements in relaxation in response to cumulative concentrations of acetylcholine may explain the associated improvement in endothelial function. Combi- nation treatment with a transdermal patch exhibited a synergistic therapeutic effect. Such favorable cardiovascular effects with nitric oxide donors and β-blockade combination through a transdermal patch may provide long-term cardiovascular protection during anti-hypertensive treatment.展开更多
A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electroc...A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electrochemical properties are investigated exercising the cyclic voltammetry and square wave voltammetry (SWV). Enhanced peak current associated with bisoprolol fumarate oxidation at EPPGE is due to its better electron transfer property. Quantification of bisoprolol fumarate was carried out at pH 7.2 at both the pyrolytic graphite electrodes. Well-defined peak has been observed at ~ 792 and 954 mV at EPPGE and BPPGE respectively for bisoprolol fumarate oxidation. The detection limit is found to be 2.8 × 10–7 M and 7.3 × 10–7 M for EPPGE and BPPGE respectively. A comparison of common quantification parameters for bisoprolol at carbon nanotube modified glassy carbon electrode and bare BPPGE and EPPGE has been made and it is observed that carbon naotube modified glassy carbon exhibits sensitivity and detection limit close to that observed at bare basal plane pyrolytic graphite electrode. The method developed is applicable for determination of bisoprolol fumarate in pharmaceutical preparations and real samples.展开更多
Objective:To explore the effect of bisoprolol in combined with trimetazidine on the cardiac function rehabilitation in patients with chronic heart failure (CHF).Methods: A total of 84 patients with CHF who were admitt...Objective:To explore the effect of bisoprolol in combined with trimetazidine on the cardiac function rehabilitation in patients with chronic heart failure (CHF).Methods: A total of 84 patients with CHF who were admitted in our hospital from November, 2015 to October, 2016 were included in the study and randomized into the observation group and the control group. The patients in the two groups were given oxygen inhalation, lipid regulation, diuresis, ARB, and other routine treatments. Digitalis preparations were given for those who had poor cardiac function, and bisoprolol were orally administrated in the same time. On the above basis, the patients in the observation group were given trimetazidine dihydrochloride tablets, continuously for 3 months. The morning fasting peripheral venous blood before and after treatment in the two groups was collected. CRP, IL-6, TNF-α, BNP, NE, AngⅡ, ANP, ALD, and ET were detected. The cardiac color Doppler ultrasound diagnostic apparatus was used to detect LVPWT, PWS, PWD, IVSS, and IVMI.Results: CRP, IL-6, TNF-α, and BNP levels after treatment in the observation group were significantly lower than those in the control group. NE, AngⅡ, ANP, ALD, and ET levels after treatment in the observation group were significantly lower than those in the control group. LVPWT, PWS, PWD, IVSS, and IVMI levels after treatment in the observation group were significantly lower than those in the control group.Conclusions: Bisoprolol in combined with trimetazidine can significantly reduce the inflammatory reaction in patients with CHF, and effectively regulate the neuroendocrine stability in order to reverse or reduce VR and improve the left ventricular function.展开更多
Objective:To study the effect of trimetazidine combined with bisoprolol on the cardiac function, ventricular remodeling and neuroendocrine factors in patients with chronic heart failure.Methods: A total of 52 patients...Objective:To study the effect of trimetazidine combined with bisoprolol on the cardiac function, ventricular remodeling and neuroendocrine factors in patients with chronic heart failure.Methods: A total of 52 patients with chronic heart failure who were treated in our hospital between January 2012 and November 2015 were collected and divided into the control group (n=26) who received bisoprolol therapy and the observation group (n=26) who received trimetazidine combined with bisoprolol therapy according to the double-blind randomized control method, and both groups were treated for 3 months. Before treatment and after 3 months of treatment, cardiac color Doppler diasonograph was used to determine the levels of cardiac function parameters and ventricular remodeling parameters, and RIA method was used to determine the levels if peripheral blood neuroendocrine factors.Results: Before treatment, the differences in cardiac function, ventricular remodeling and neuroendocrine factor levels were not statistically significant between two groups of patients. After 3 months of treatment, cardiac function parameters LVEDd and LVESD levels of observation group were lower than those of control group while LVEF level was higher than that of control group, and ventricular remodeling parameters LVPWT, IVSS, PWD, PWS and LVMI levels were lower than those of control group;peripheral blood neuroendocrine factors NE, ALD, AngⅡ, ANP and ET contents of observation group were lower than those of control group.Conclusion:Trimetazidine combined with bisoprolol can optimize the cardiac function, suppress the ventricular remodeling process and regulate the neuroendocrine factor secretion in patients with chronic heart failure, and it contributes to the patients' overall optimization.展开更多
[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcita...[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcitation=277 nm andλemission=596 nm,with the increase of CCu2+,the fluorescence signal intensity of bisoprolol fumarate weakened,and the difference between the fluorescence intensity of bisoprolol fumarate itself and the fluorescence intensity of the test solution after the quencher Cu2+was added(ΔF)and Cbisoprolol fumarate showed a good linear relationship.[Results]In the range of 15.39-76.93μg/mL,ΔF=146.7 Cbisoprolol fumarate+482.1,r=0.9988,and the detection limit is 0.1391μg/mL.[Conclusions]The fluorescence quenching method has been applied to the determination of actual samples with a recovery rate of 99.9%and an RSD of 2.7%.The results are satisfactory.展开更多
Background:Resting heart rate(RHR)is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients.Bisoprolol fumarate,a second-generation beta-adrenoreceptor bl...Background:Resting heart rate(RHR)is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients.Bisoprolol fumarate,a second-generation beta-adrenoreceptor blockers(β-blocker)is commonly prescribed drug to manage hypertension.The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease(CAD)patients from the CAD treated with bisoprolol(BISO-CAD)study who had comorbid hypertension.Methods::We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study(n=866),which was a phase IV,multination,multi-center,single-arm,observational study carried out from October 2011 to July 2015 across China,South Korea,and Vietnam.Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome(CCCO),the results were presented as adjusted odds ratio(OR)along with 95%confidence interval(CI)and adjusted P value.Results::A total of 681 patients(mean age:64.77±10.33 years)with hypertension from BISO-CAD study were included in the analysis.Bisoprolol improved CCCOs in CAD patients with comorbid hypertension,with RHR<65 and<70 beats/min compared with RHR≥65 and≥75 beats/min,respectively,in the efficacy analysis(EA)set.In addition,it lowered RHR in both intent-to-treat(ITT)and EA groups after 6,12,and 18 months of treatment.Further,RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients(adjusted OR:4.34;95%CI:1.19-15.89;P=0.03).Also,events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR<69 beats/min in ITT patients.Conclusion::Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence,improve CCCO without affecting their blood pressure.展开更多
基金‘863'High Technology R&D Project of Ministry of Science and Technology of China(Grant No.2004AA2Z3073).
文摘The objective of the present study is to examine cardiovascular protective action of a newly developed transdermal patch by incorporating bisoprolol and isosorbide dinitrate in spontaneously hypertensive rats. As the combination therapy with these two synergistic drugs at low doses through a suitable form of administration could provide optimal therapeutic benefit, we further evaluated the effects of a 42 d period of anti-hypertensive treatment in spontaneously hypertensive rats. Rats were divided into the following five groups： control （blank patch）, bisoprolol fumarate tablets （BP-FT, 20.0 mg/kg, i.g.）, bisoprolol transdermal patch （BP-TP, 20.0 mg/kg）, isosorbide dinitrate transdermal patch （ISDN-TP, 20.0 mg/kg）, and the combination of BP and ISDN in a transdermal patch at low doses （8 and 12 mg/kg, respectively）. The effects of treatment were evaluated via biochemical indicators related to cardiovascular protection, structure and function. The combination therapy had synergistic anti-hypertensive effects and significantly reduced blood pressure with the benefit of controlling blood pressure variability compared to BP-FT and BP-TP. The combined treatment also reduced heart rate as well as BP-FT and BP-TP, while ISDN-TP had no evident effects on blood pressure, heart rate, and cardiovascular protection. Combination therapy was superior to BP-TP and BP-FT at increasing blood atrial natriuretic peptide and nitric oxide, while also reducing cardiac hydroxyproline and endothelin-1 with no difference in blood endothelin-1 and cardiac malondialdehyde levels. Cardiovascular remodeling differed among the groups, with the combination therapy reducing cardiac hypertrophy and the aortic media/lumen ratio. The consequential improvements in relaxation in response to cumulative concentrations of acetylcholine may explain the associated improvement in endothelial function. Combi- nation treatment with a transdermal patch exhibited a synergistic therapeutic effect. Such favorable cardiovascular effects with nitric oxide donors and β-blockade combination through a transdermal patch may provide long-term cardiovascular protection during anti-hypertensive treatment.
文摘A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electrochemical properties are investigated exercising the cyclic voltammetry and square wave voltammetry (SWV). Enhanced peak current associated with bisoprolol fumarate oxidation at EPPGE is due to its better electron transfer property. Quantification of bisoprolol fumarate was carried out at pH 7.2 at both the pyrolytic graphite electrodes. Well-defined peak has been observed at ~ 792 and 954 mV at EPPGE and BPPGE respectively for bisoprolol fumarate oxidation. The detection limit is found to be 2.8 × 10–7 M and 7.3 × 10–7 M for EPPGE and BPPGE respectively. A comparison of common quantification parameters for bisoprolol at carbon nanotube modified glassy carbon electrode and bare BPPGE and EPPGE has been made and it is observed that carbon naotube modified glassy carbon exhibits sensitivity and detection limit close to that observed at bare basal plane pyrolytic graphite electrode. The method developed is applicable for determination of bisoprolol fumarate in pharmaceutical preparations and real samples.
文摘Objective:To explore the effect of bisoprolol in combined with trimetazidine on the cardiac function rehabilitation in patients with chronic heart failure (CHF).Methods: A total of 84 patients with CHF who were admitted in our hospital from November, 2015 to October, 2016 were included in the study and randomized into the observation group and the control group. The patients in the two groups were given oxygen inhalation, lipid regulation, diuresis, ARB, and other routine treatments. Digitalis preparations were given for those who had poor cardiac function, and bisoprolol were orally administrated in the same time. On the above basis, the patients in the observation group were given trimetazidine dihydrochloride tablets, continuously for 3 months. The morning fasting peripheral venous blood before and after treatment in the two groups was collected. CRP, IL-6, TNF-α, BNP, NE, AngⅡ, ANP, ALD, and ET were detected. The cardiac color Doppler ultrasound diagnostic apparatus was used to detect LVPWT, PWS, PWD, IVSS, and IVMI.Results: CRP, IL-6, TNF-α, and BNP levels after treatment in the observation group were significantly lower than those in the control group. NE, AngⅡ, ANP, ALD, and ET levels after treatment in the observation group were significantly lower than those in the control group. LVPWT, PWS, PWD, IVSS, and IVMI levels after treatment in the observation group were significantly lower than those in the control group.Conclusions: Bisoprolol in combined with trimetazidine can significantly reduce the inflammatory reaction in patients with CHF, and effectively regulate the neuroendocrine stability in order to reverse or reduce VR and improve the left ventricular function.
文摘Objective:To study the effect of trimetazidine combined with bisoprolol on the cardiac function, ventricular remodeling and neuroendocrine factors in patients with chronic heart failure.Methods: A total of 52 patients with chronic heart failure who were treated in our hospital between January 2012 and November 2015 were collected and divided into the control group (n=26) who received bisoprolol therapy and the observation group (n=26) who received trimetazidine combined with bisoprolol therapy according to the double-blind randomized control method, and both groups were treated for 3 months. Before treatment and after 3 months of treatment, cardiac color Doppler diasonograph was used to determine the levels of cardiac function parameters and ventricular remodeling parameters, and RIA method was used to determine the levels if peripheral blood neuroendocrine factors.Results: Before treatment, the differences in cardiac function, ventricular remodeling and neuroendocrine factor levels were not statistically significant between two groups of patients. After 3 months of treatment, cardiac function parameters LVEDd and LVESD levels of observation group were lower than those of control group while LVEF level was higher than that of control group, and ventricular remodeling parameters LVPWT, IVSS, PWD, PWS and LVMI levels were lower than those of control group;peripheral blood neuroendocrine factors NE, ALD, AngⅡ, ANP and ET contents of observation group were lower than those of control group.Conclusion:Trimetazidine combined with bisoprolol can optimize the cardiac function, suppress the ventricular remodeling process and regulate the neuroendocrine factor secretion in patients with chronic heart failure, and it contributes to the patients' overall optimization.
基金Project for Improving Basic Research Ability of Middle Aged and Young Teachers in Colleges and Universities of Guangxi in 2017(2017KY0284)Project of Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine(GXZYKF2019-7)+2 种基金Program of Key Laboratory for Extraction and Purification and Quality Analysis of TCM in 2017(J1700208)Project of Guangxi University of Chinese Medicine(YB14004)Collaborative Innovation Center of Zhuang and Yao Ethnic Medicine([2013]No.20).
文摘[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcitation=277 nm andλemission=596 nm,with the increase of CCu2+,the fluorescence signal intensity of bisoprolol fumarate weakened,and the difference between the fluorescence intensity of bisoprolol fumarate itself and the fluorescence intensity of the test solution after the quencher Cu2+was added(ΔF)and Cbisoprolol fumarate showed a good linear relationship.[Results]In the range of 15.39-76.93μg/mL,ΔF=146.7 Cbisoprolol fumarate+482.1,r=0.9988,and the detection limit is 0.1391μg/mL.[Conclusions]The fluorescence quenching method has been applied to the determination of actual samples with a recovery rate of 99.9%and an RSD of 2.7%.The results are satisfactory.
基金This study was funded by Merck Serono Co.,Ltd,an affiliate of Merck KGaA,Darmstadt,Germany.
文摘Background:Resting heart rate(RHR)is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients.Bisoprolol fumarate,a second-generation beta-adrenoreceptor blockers(β-blocker)is commonly prescribed drug to manage hypertension.The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease(CAD)patients from the CAD treated with bisoprolol(BISO-CAD)study who had comorbid hypertension.Methods::We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study(n=866),which was a phase IV,multination,multi-center,single-arm,observational study carried out from October 2011 to July 2015 across China,South Korea,and Vietnam.Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome(CCCO),the results were presented as adjusted odds ratio(OR)along with 95%confidence interval(CI)and adjusted P value.Results::A total of 681 patients(mean age:64.77±10.33 years)with hypertension from BISO-CAD study were included in the analysis.Bisoprolol improved CCCOs in CAD patients with comorbid hypertension,with RHR<65 and<70 beats/min compared with RHR≥65 and≥75 beats/min,respectively,in the efficacy analysis(EA)set.In addition,it lowered RHR in both intent-to-treat(ITT)and EA groups after 6,12,and 18 months of treatment.Further,RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients(adjusted OR:4.34;95%CI:1.19-15.89;P=0.03).Also,events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR<69 beats/min in ITT patients.Conclusion::Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence,improve CCCO without affecting their blood pressure.
