UV/H2O2 and UV/peroxodisulfate （PDS） processes were adopted to degrade a typical β-blocker atenolol （ATL）. The degradation efficiencies under various operational parameters （oxidant dosage, pH, HCO3-, humic acid...UV/H2O2 and UV/peroxodisulfate （PDS） processes were adopted to degrade a typical β-blocker atenolol （ATL）. The degradation efficiencies under various operational parameters （oxidant dosage, pH, HCO3-, humic acid （HA）, NO3- , and Cl-） were compared. Principal factor analysis was also performed with a statistical method for the two processes. It was found that increasing the specific dosage of the two peroxides （[peroxide]0/[ATL]0 ） ranging from 1：1 to 8：1 led to a faster degradation rate but also higher peroxide residual. Within the pH range 3-11, the optimum pH was 7 for the UV/PDS process and elevating pH benefitted the UV/H 2O2 process. The presence of HCO3- , HA, and Cl adversely affected ATL oxidation in both processes. The NO3- concentration 1-3 mmol/L accelerated the destruction of ATL by the UV/PDS process, but further increase of NO3- concentration retarded the degradation process, contrary to the case in the UV/H2O2 process. The rank orders of effects caused by the six operational parameters were pH ≈ specific dosage 〉 [HA]0 〉 [NO3-]0 〉 [HCO3-]0 〉 [Cl-]0 for the UV/H2O2 process and specific dosage 〉 pH 〉 [HA]0 〉 [NO3-]0 〉 [HCO3-]0 〉[Cl-]0 for the UV/PDS process. The UV/PDS process was more sensitive to changes in operational parameters than the UV/H2O2 process but more efficient in ATL removal under the same conditions.展开更多
2-Acryloxyacetophenone （AAP） was prepared and subjected to suspension polymerization with methyl methacrylate （MMA） using azobisisobutyronitrile （AIBN） as free radical initiator. The differently sulfonated AAP-M...2-Acryloxyacetophenone （AAP） was prepared and subjected to suspension polymerization with methyl methacrylate （MMA） using azobisisobutyronitrile （AIBN） as free radical initiator. The differently sulfonated AAP-MMA cross-linked copolymer cationic exchange resins were prepared by sulfonation with concentrated sulphuric acid at 70 ~C. Several characteristics of the prepared resins were evaluated, i.e. FTIR, the ion-exchange capacity （IEC）, thermo gravimetric analysis （TGA）, particle size distribution and microscopic morphology. The resin characteristics were altered with degree of sulfonation, providing that differently sulfonated resins could be prepared. The behavior of atenolol （ATL） loading and in vitro release in the USP stimulated gastric and intestinal fluids of the obtained resins were evaluated. The drug loaded in the resin increased with increasing degree of sulfonation and hence the drug binding site in resin employed. The drug release was lower from the resins with higher content of sulfonic group due to the increase in the diffusive path depth. The drug release was a little lower in stimulated gastric fluid （SGF） than in stimulated intestinal fluids （SIF）. The basic groups, ionized to a little greater extent in SGF and preferred binding with the resin rather than releasing. Hence, the differently sulfonated resins could be utilized as novel carriers for drug delivery.展开更多
Three simple,specific,accurate and precise spectrophotometric methods are developed for simultaneous determination of amlodipine besylate(AM)and atenolol(AT)in tablets.The first method is dual wavelength spectrophotom...Three simple,specific,accurate and precise spectrophotometric methods are developed for simultaneous determination of amlodipine besylate(AM)and atenolol(AT)in tablets.The first method is dual wavelength spectrophotometry(DW).The second method is ratio subtraction(RS)which depends on subtraction of the plateau values from the ratio spectrum,coupled to first derivative of ratio spectra(1 DD).The third method applies bivariate calibration method using 210and 225nm as an optimum pair of wavelength for amlodipine and atenolol.The calibration curves are linear over the concentration range of 4~40μg·mL-1 for both drugs.The specificity of the developed methods is investigated by analyzing laboratory prepared mixtures of the two drugs and their combined dosage form.The two methods are validated as per ICH guidelines and can be applied for routine quality control testing.展开更多
Polypill is a fixed-dose combination (FDC) containing three or more drugs in a single pill with the intention of reducing the number of tablets or capsules that need to be taken. Developing a single analytical method ...Polypill is a fixed-dose combination (FDC) containing three or more drugs in a single pill with the intention of reducing the number of tablets or capsules that need to be taken. Developing a single analytical method for the estimation of individual drugs in a Polypill is very challenging, due to the formation of drug-drug and drug-excipients interaction impurities. Here an attempt was made to develop a new, sensitive, single stability-indicating HPLC method for the simultaneous quantitative determination of Aspirin (ASP) Atorvastatin (ATV), Atenolol (ATL) and Losartan potassium (LST) in a polypill form in the presence of degradation products. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination of buffer and Acetonitrile. Buffer consists of 0.1% Orthophosphoric acid (pH 2.9), delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 230 nm with a flow rate of 1.0 mL/min. The retention times of Atenolol, Aspirin, Losartan potassium, and Atorvastatin were 3.3, 7.6, 10.7 and 12.9 min respectively. The combination drug product are exposed to thermal, acid/base hydrolytic, humidity and oxidative stress conditions, and the stressed samples were analyzed by proposed method. The method was validated with respect to linearity;the method was linear in the range of 37.5 to 150.0 μg/mL for ASP, 5.0 to 20.0 μg/mL for ATV and 25.0 to 100.0 μg/mL for ATL and LST. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. The validated method was successfully applied to the analysis of Starpill tablets constituting all the four drugs;the percentage recoveries obtained were 99.60% for ASP, 99.30% for ATV, 99.41% for ATL and 99.62% for LST.展开更多
Three types of metal ions barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)complexity of ATN drug have been prepared and characterized using molar conductance method,FT-IR,electronic,and 1H-NMR analysis measurements.The chemical an...Three types of metal ions barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)complexity of ATN drug have been prepared and characterized using molar conductance method,FT-IR,electronic,and 1H-NMR analysis measurements.The chemical and physical results for all atenolol complexes are agreement with the speculated structures.For the divalent(Ba&Ni)and trivalent(Ce)metal atenolol a molar ratio 1∶2 was established.Qualitative chemical analysis showed that for the divalent metal complexes,the chloride ions are not involved in the complexes,suggesting that all of these complexes,[Ba(ATN)2]·2 H2O and[Ni(ATN)2(H2O)2]·4 H2O are neutral.However,for the cerium(Ⅲ)complex,[Ce(ATN)2(NO3)]·3 H2O,the nitrate group is existed inside the coordination sphere.ATN make astable metal complexity with barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)ions.Electronic absorption analysis of Atenolol give two fundamental peaks at 225 nm and 274 nm refers to variation in transition electrons of ligand,UV spectral analysis of the three complexity obtained give asymmetric broad band in the range 200~400 nm,the reults are convenient with the suggestion of metal-nitrogen and metal-oxygen bonds.The infrared analysis data proved that ATN act as bidentate ligand through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.Nickel(Ⅱ)and cerium(Ⅲ)complexity make six-coordinate geometry,whereas the barium(Ⅱ)complex exhibit four-coordinate geometry.Ni(Ⅱ)-ATN complex has an effective magnetic moment equal 3.12 B.M,that is assigned to octahedral structure.The 1H-NMR spectral results of Ba(Ⅱ)-ATN complexity give strong signal at^4.00 ppm due to protons of-CH2 that influenced by low degree due to complexity.These results confirm the position of chelation through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.展开更多
The pharmaceuti-cally active com-pound atenolol,a kind of β-blockers,may result in ad-verse effects both for human health and ecosystems if it is excreted to the surface water resources.To e ectively remove atenolol ...The pharmaceuti-cally active com-pound atenolol,a kind of β-blockers,may result in ad-verse effects both for human health and ecosystems if it is excreted to the surface water resources.To e ectively remove atenolol in the environ-ment,both direct and indirect photodegradation,driven by sunlight play an important role.Among indirect photodegradation,singlet oxygen(^(1)O_(2)),as a pivotal reactive species,is likely to determine the fates of atenolol.Nevertheless,the kinetic information on the re-action of atenolol with singlet oxygen has not been well investigated and the reaction rate constant is still ambiguous.Herein,the reaction rate constant of atenolol with singlet oxy-gen is investigated directly through observing the decay of the^(1)O_(2)phosphorescence at 1270 nm.It is determined that the reaction rate constant between atenolol and^(1)O_(2)is 7.0×10^(5)(mol/L)^(-1)·s^(-1)in D2O,8.0×10^(6)(mol/L)^(-1)·s^(-1)in acetonitrile,and 8.4×10^(5)(mol/L)^(-1)·s^(-1)in EtOH,respectively.Furthermore,the solvent effects on the title reaction were also inves-tigated.It is revealed that the solvents with strong polarity and weak hydrogen donating ability are suitable to achieve high rate constant values.These kinetics information on the reaction of atenolol with singlet oxygen may provide fundamental knowledge to the indirect photodegradation of β-blockers.展开更多
Atenolol diffusion through synthetic membrane, cloned human epidermis, and cat ear skin was performed utilizing a Franz diffusion cell. Transdermal drug diffusion enhancers’ ethanol, glycerol, propylene glycol, polys...Atenolol diffusion through synthetic membrane, cloned human epidermis, and cat ear skin was performed utilizing a Franz diffusion cell. Transdermal drug diffusion enhancers’ ethanol, glycerol, propylene glycol, polysorbate 80 and Dimethyl isosorbide (DMI) were added to the topical formulations and tested for their ability to enhance drug permeation through the test membranes. Topical formulation with penetration enhancers showed a rapid burst of atenolol diffusion for the first two hours (35.5 to 40 μg/ml) followed by a zero-order sustained diffusion of 2.7 μg/cm2/h of atenolol for up to twenty-four hours after application to test membranes. Increased atenolol flux through different test membranes was greatest for synthetic membrane. The topical application of the optimized atenolol formulation to cat skin containing permeation enhancers aided transdermal atenolol drug delivery to treat cats with hypertrophic obstructive cardiomyopathy. The optimum topical formulation demonstrated two fluxes through cat skin, the burst flux (15.7 μg/cm2/h) and a sustained flux (2.7 μg/cm2/h). Measured atenolol concentrations in cats at 3, 6 and 12 hours after transdermal atenolol application were 432.7 ng/ml ± 323.3, 262.4 ng/ml ± 150.1, and 253.3 ng/ml ± 133.6 respectively. Six of 7 cats achieved therapeutic serum atenolol levels (260 ng/ml) for at least one time point. Five of 7 cats had therapeutic serum atenolol concentrations 3 hours post-atenolol. At the 6 hours post-atenolol time point, only 2 had a therapeutic serum atenolol concentration while at 12 hours post-atenolol dosing, 4 of 7 cats had therapeutic serum atenolol concentrations. Transdermal atenolol administered at 25 mg q12h resulted in clinically therapeutic serum atenolol concentrations in the majority of healthy cats. The optimum transdermal formulation enabled good drug delivery feasible for transdermal application in a clinical trial in cats.展开更多
Objective:This study is aimed to explore the effect of triazole fungicide tebuconazole(TEB)exposure on the oral absorption behavior of atenolol(AT),based on the homeostasis of bile acids(BAs).Methods:TEB was daily gav...Objective:This study is aimed to explore the effect of triazole fungicide tebuconazole(TEB)exposure on the oral absorption behavior of atenolol(AT),based on the homeostasis of bile acids(BAs).Methods:TEB was daily gavaged to rats with 3 mg/kg dose for 28 days to establish the TEB-exposure rat model.The amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in the small intestine contents of normal and TEB-exposure rats were detected by LC-MS/MS.AT(10 mg/kg)were gavaged to the normal and TEB-exposure rats,and then blood were collected from orbital venous plexus at predetermined time-points.The concentration of AT in plasma was detected by LC-MS/MS,and the pharmacokinetic parameters were calculated by the DAS pharmacokinetic software.An intestinal circulation perfusion model was established in normal rats,and perfused with the perfusates containing the model drug of fluorescein and the BAs with the same compositions as the normal/TEB-exposure rats.After perfusion,the absorption and permeability of fluorescein in intestine were detected,as well as the oxidative stress status and ZO-1 expression level in the intestinal tissues.Results:Compared with normal rats,TEB-exposure increased the amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in intestine significantly(P<0.001).In TEB-exposure rats,the maximum plasma concentration and area under the curve of AT were increased significantly than those of normal rats(P<0.05),and the peak time was significantly delayed(P<0.05).The TEB-induced BAs homeostasis perturbance increased intestinal permeability,and this effect was associated with the elevation of oxidative stress and the down-regulation of intercellular tight junction proteins in intestinal tissues.Conclusion:TEB-exposure can affect the oral absorption behavior of AT,which is probably related with the intestinal BAs homeostasis perturbance,thus it might affect the clinical efficacy and safety of this drug.展开更多
In this paper functionalized multiwall carbon nanotubes (FMWCNT) were modified using atenolol as a class of drugs that were used in cardiovascular diseases containing reactable nitrogen, which could attach chemically ...In this paper functionalized multiwall carbon nanotubes (FMWCNT) were modified using atenolol as a class of drugs that were used in cardiovascular diseases containing reactable nitrogen, which could attach chemically to functionalized MWCNT. This product was characterized by Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. These spectrums proved the existence of nitrogen atoms of amide due to new functional group. The morphology were also determined by scanning electron microscopy (SEM) and showed that this product was synthesized in the nanometer dimension. Thermal gravimetery (TGA) analysis was also used to evaluate thermal properties.展开更多
The objective of the study was to evaluate the drug-drug interaction studies of levoceterizine with atenolol. Calibration curve studies of working standard solutions of levocetirizine and atenolol （0.01-0.1 mmol） we...The objective of the study was to evaluate the drug-drug interaction studies of levoceterizine with atenolol. Calibration curve studies of working standard solutions of levocetirizine and atenolol （0.01-0.1 mmol） were scanned. Maxima appeared at 231 nm for levocetirizine and 224 nm for atenolol. The calibration curve obeyed Beer Lambert＇s Law. Lone availabilities of both the drugs were studied in pH 1, pH 4, pH 7.4 and pH 9 at 37℃ on B.P. （British Pharmacopoeia） dissolution apparatus. To study the drug-drug interaction of levocetirizine （5 mg tablet） and atenolol （100 mg tablet）, both the drugs were introduced to the dissolution apparatus in simulated gastric juice （pH 1）, pH 4, pH 7.4 and pH 9 at 37℃ at zero time and measured the absorbance maxima of both the drugs at the corresponding wavelength. Graphs were plotted for availability percentage （%） of drug versus time at each set of experiment. The availability percentage （%） of levocetirizine in the buffers of pH simulated to gastric pH 4, pH 7.4 and pH 9 in the presence of atenolol was 436.78%, 376.90%, 436.78% and 436.78%, respectively, but the availability of atenolol was increased up to 214.80%, 212.96%, 214.93% and 231.51% in simulated to gastric pH and in the buffers ofpH 4, pH 7.4 and pH 9, respectively. On the basis of these studies, it is concluded that levocetirizine forms a charge-complex with atenolol; therefore, co-administration of these drugs should be avoided.展开更多
目的:分析选择性β_(1)受体阻滞剂治疗高血压的有效性和安全性,进一步更新选择性β_(1)受体阻滞剂的循证医学证据。方法:计算机检索中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、Embase、Coc...目的:分析选择性β_(1)受体阻滞剂治疗高血压的有效性和安全性,进一步更新选择性β_(1)受体阻滞剂的循证医学证据。方法:计算机检索中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、Embase、Cochrane Library,搜集关于选择性β_(1)受体阻滞剂治疗高血压患者的随机对照试验,检索时间均为建库至2024年5月。由两名研究者独立进行文献进行筛选、提取资料并评估纳入研究的偏倚风险,采用Cochrane偏倚风险工具对纳入研究进行质量评价,采用R4.4.0软件进行网状Meta分析,计算各结局指标的累积排序概率图下面积(the surface under the cumulative ranking,SUCRA)以比较不同干预措施的有效性与安全性。结果:SUCRA值排序结果显示,在降低收缩压方面:比索洛尔(79.33%)>阿替洛尔(57.46%)>美托洛尔缓释剂(51.12%)>美托洛尔速释剂(12.08%);降低舒张压方面:压比索洛尔(77.38%)>阿替洛尔(65.63%)>美托洛尔缓释剂(51.41%)>美托洛尔速释剂(5.57%);降低24 h动态收缩压方面:比索洛尔(92.44%)>美托洛尔速释剂(54.09%)>美托洛尔缓释剂(52.47%)>阿替洛尔(1.01%);降低24 h动态舒张压方面:比索洛尔(95.24%)>美托洛尔速释剂(52.52%)>美托洛尔缓释剂(46.82%)>阿替洛尔(5.4%);降低心率幅度方面:比索洛尔(97.88%)>阿替洛尔(66.98%)>美托洛尔缓释剂(22.72%)>美托洛尔速释剂(12.42%);降低24 h动态心率方面:美托洛尔缓释剂(69.49%)>比索洛尔(54.97%)>阿替洛尔(39.39%)>美托洛尔速释剂(36.17%);不良反应发生率方面:阿替洛尔(81.38%)>美托洛尔缓释剂(54.86%)>比索洛尔(48.97%)>美托洛尔速释剂(14.79%)。结论:比索洛尔、阿替洛尔、美托洛尔速释剂和美托洛尔缓释剂治疗高血压时均有明显的有效性,其中比索洛尔的有效性最为显著,而阿替洛尔的总不良反应发生率较高,临床使用时应给予关注。展开更多
文摘UV/H2O2 and UV/peroxodisulfate （PDS） processes were adopted to degrade a typical β-blocker atenolol （ATL）. The degradation efficiencies under various operational parameters （oxidant dosage, pH, HCO3-, humic acid （HA）, NO3- , and Cl-） were compared. Principal factor analysis was also performed with a statistical method for the two processes. It was found that increasing the specific dosage of the two peroxides （[peroxide]0/[ATL]0 ） ranging from 1：1 to 8：1 led to a faster degradation rate but also higher peroxide residual. Within the pH range 3-11, the optimum pH was 7 for the UV/PDS process and elevating pH benefitted the UV/H 2O2 process. The presence of HCO3- , HA, and Cl adversely affected ATL oxidation in both processes. The NO3- concentration 1-3 mmol/L accelerated the destruction of ATL by the UV/PDS process, but further increase of NO3- concentration retarded the degradation process, contrary to the case in the UV/H2O2 process. The rank orders of effects caused by the six operational parameters were pH ≈ specific dosage 〉 [HA]0 〉 [NO3-]0 〉 [HCO3-]0 〉 [Cl-]0 for the UV/H2O2 process and specific dosage 〉 pH 〉 [HA]0 〉 [NO3-]0 〉 [HCO3-]0 〉[Cl-]0 for the UV/PDS process. The UV/PDS process was more sensitive to changes in operational parameters than the UV/H2O2 process but more efficient in ATL removal under the same conditions.
基金The University Grants Commission,New Delhi for its funding of this workIndian Institute of Science,Bangalore for its instrumental support+2 种基金Department of Physics,Sri Venkateswara University,Tirupathi,for its assistance in the SEM studyUGC,New Delhi for its support under SAPDST,New Delhi for its support under FIST
文摘2-Acryloxyacetophenone （AAP） was prepared and subjected to suspension polymerization with methyl methacrylate （MMA） using azobisisobutyronitrile （AIBN） as free radical initiator. The differently sulfonated AAP-MMA cross-linked copolymer cationic exchange resins were prepared by sulfonation with concentrated sulphuric acid at 70 ~C. Several characteristics of the prepared resins were evaluated, i.e. FTIR, the ion-exchange capacity （IEC）, thermo gravimetric analysis （TGA）, particle size distribution and microscopic morphology. The resin characteristics were altered with degree of sulfonation, providing that differently sulfonated resins could be prepared. The behavior of atenolol （ATL） loading and in vitro release in the USP stimulated gastric and intestinal fluids of the obtained resins were evaluated. The drug loaded in the resin increased with increasing degree of sulfonation and hence the drug binding site in resin employed. The drug release was lower from the resins with higher content of sulfonic group due to the increase in the diffusive path depth. The drug release was a little lower in stimulated gastric fluid （SGF） than in stimulated intestinal fluids （SIF）. The basic groups, ionized to a little greater extent in SGF and preferred binding with the resin rather than releasing. Hence, the differently sulfonated resins could be utilized as novel carriers for drug delivery.
文摘Three simple,specific,accurate and precise spectrophotometric methods are developed for simultaneous determination of amlodipine besylate(AM)and atenolol(AT)in tablets.The first method is dual wavelength spectrophotometry(DW).The second method is ratio subtraction(RS)which depends on subtraction of the plateau values from the ratio spectrum,coupled to first derivative of ratio spectra(1 DD).The third method applies bivariate calibration method using 210and 225nm as an optimum pair of wavelength for amlodipine and atenolol.The calibration curves are linear over the concentration range of 4~40μg·mL-1 for both drugs.The specificity of the developed methods is investigated by analyzing laboratory prepared mixtures of the two drugs and their combined dosage form.The two methods are validated as per ICH guidelines and can be applied for routine quality control testing.
文摘Polypill is a fixed-dose combination (FDC) containing three or more drugs in a single pill with the intention of reducing the number of tablets or capsules that need to be taken. Developing a single analytical method for the estimation of individual drugs in a Polypill is very challenging, due to the formation of drug-drug and drug-excipients interaction impurities. Here an attempt was made to develop a new, sensitive, single stability-indicating HPLC method for the simultaneous quantitative determination of Aspirin (ASP) Atorvastatin (ATV), Atenolol (ATL) and Losartan potassium (LST) in a polypill form in the presence of degradation products. Efficient chromatographic separation was achieved on a C18 stationary phase with simple mobile phase combination of buffer and Acetonitrile. Buffer consists of 0.1% Orthophosphoric acid (pH 2.9), delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 230 nm with a flow rate of 1.0 mL/min. The retention times of Atenolol, Aspirin, Losartan potassium, and Atorvastatin were 3.3, 7.6, 10.7 and 12.9 min respectively. The combination drug product are exposed to thermal, acid/base hydrolytic, humidity and oxidative stress conditions, and the stressed samples were analyzed by proposed method. The method was validated with respect to linearity;the method was linear in the range of 37.5 to 150.0 μg/mL for ASP, 5.0 to 20.0 μg/mL for ATV and 25.0 to 100.0 μg/mL for ATL and LST. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. The validated method was successfully applied to the analysis of Starpill tablets constituting all the four drugs;the percentage recoveries obtained were 99.60% for ASP, 99.30% for ATV, 99.41% for ATL and 99.62% for LST.
文摘Three types of metal ions barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)complexity of ATN drug have been prepared and characterized using molar conductance method,FT-IR,electronic,and 1H-NMR analysis measurements.The chemical and physical results for all atenolol complexes are agreement with the speculated structures.For the divalent(Ba&Ni)and trivalent(Ce)metal atenolol a molar ratio 1∶2 was established.Qualitative chemical analysis showed that for the divalent metal complexes,the chloride ions are not involved in the complexes,suggesting that all of these complexes,[Ba(ATN)2]·2 H2O and[Ni(ATN)2(H2O)2]·4 H2O are neutral.However,for the cerium(Ⅲ)complex,[Ce(ATN)2(NO3)]·3 H2O,the nitrate group is existed inside the coordination sphere.ATN make astable metal complexity with barium(Ⅱ),nickel(Ⅱ)and cerium(Ⅲ)ions.Electronic absorption analysis of Atenolol give two fundamental peaks at 225 nm and 274 nm refers to variation in transition electrons of ligand,UV spectral analysis of the three complexity obtained give asymmetric broad band in the range 200~400 nm,the reults are convenient with the suggestion of metal-nitrogen and metal-oxygen bonds.The infrared analysis data proved that ATN act as bidentate ligand through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.Nickel(Ⅱ)and cerium(Ⅲ)complexity make six-coordinate geometry,whereas the barium(Ⅱ)complex exhibit four-coordinate geometry.Ni(Ⅱ)-ATN complex has an effective magnetic moment equal 3.12 B.M,that is assigned to octahedral structure.The 1H-NMR spectral results of Ba(Ⅱ)-ATN complexity give strong signal at^4.00 ppm due to protons of-CH2 that influenced by low degree due to complexity.These results confirm the position of chelation through the N atom of the-NH group and O atom of the deprotonated alcoholic OH group.
基金This work was supported by the National Natural Science Foundation of China(No.21773013).
文摘The pharmaceuti-cally active com-pound atenolol,a kind of β-blockers,may result in ad-verse effects both for human health and ecosystems if it is excreted to the surface water resources.To e ectively remove atenolol in the environ-ment,both direct and indirect photodegradation,driven by sunlight play an important role.Among indirect photodegradation,singlet oxygen(^(1)O_(2)),as a pivotal reactive species,is likely to determine the fates of atenolol.Nevertheless,the kinetic information on the re-action of atenolol with singlet oxygen has not been well investigated and the reaction rate constant is still ambiguous.Herein,the reaction rate constant of atenolol with singlet oxy-gen is investigated directly through observing the decay of the^(1)O_(2)phosphorescence at 1270 nm.It is determined that the reaction rate constant between atenolol and^(1)O_(2)is 7.0×10^(5)(mol/L)^(-1)·s^(-1)in D2O,8.0×10^(6)(mol/L)^(-1)·s^(-1)in acetonitrile,and 8.4×10^(5)(mol/L)^(-1)·s^(-1)in EtOH,respectively.Furthermore,the solvent effects on the title reaction were also inves-tigated.It is revealed that the solvents with strong polarity and weak hydrogen donating ability are suitable to achieve high rate constant values.These kinetics information on the reaction of atenolol with singlet oxygen may provide fundamental knowledge to the indirect photodegradation of β-blockers.
文摘Atenolol diffusion through synthetic membrane, cloned human epidermis, and cat ear skin was performed utilizing a Franz diffusion cell. Transdermal drug diffusion enhancers’ ethanol, glycerol, propylene glycol, polysorbate 80 and Dimethyl isosorbide (DMI) were added to the topical formulations and tested for their ability to enhance drug permeation through the test membranes. Topical formulation with penetration enhancers showed a rapid burst of atenolol diffusion for the first two hours (35.5 to 40 μg/ml) followed by a zero-order sustained diffusion of 2.7 μg/cm2/h of atenolol for up to twenty-four hours after application to test membranes. Increased atenolol flux through different test membranes was greatest for synthetic membrane. The topical application of the optimized atenolol formulation to cat skin containing permeation enhancers aided transdermal atenolol drug delivery to treat cats with hypertrophic obstructive cardiomyopathy. The optimum topical formulation demonstrated two fluxes through cat skin, the burst flux (15.7 μg/cm2/h) and a sustained flux (2.7 μg/cm2/h). Measured atenolol concentrations in cats at 3, 6 and 12 hours after transdermal atenolol application were 432.7 ng/ml ± 323.3, 262.4 ng/ml ± 150.1, and 253.3 ng/ml ± 133.6 respectively. Six of 7 cats achieved therapeutic serum atenolol levels (260 ng/ml) for at least one time point. Five of 7 cats had therapeutic serum atenolol concentrations 3 hours post-atenolol. At the 6 hours post-atenolol time point, only 2 had a therapeutic serum atenolol concentration while at 12 hours post-atenolol dosing, 4 of 7 cats had therapeutic serum atenolol concentrations. Transdermal atenolol administered at 25 mg q12h resulted in clinically therapeutic serum atenolol concentrations in the majority of healthy cats. The optimum transdermal formulation enabled good drug delivery feasible for transdermal application in a clinical trial in cats.
基金supported by National Natural Science Foundation of China(81874348)Academic Support Program for Top Talents of Higher Education in Anhui Province(GXBJZD2022027)Science and Technology Innovation Project of Anhui Drug Administration(AHYJ-KJ-202110)。
文摘Objective:This study is aimed to explore the effect of triazole fungicide tebuconazole(TEB)exposure on the oral absorption behavior of atenolol(AT),based on the homeostasis of bile acids(BAs).Methods:TEB was daily gavaged to rats with 3 mg/kg dose for 28 days to establish the TEB-exposure rat model.The amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in the small intestine contents of normal and TEB-exposure rats were detected by LC-MS/MS.AT(10 mg/kg)were gavaged to the normal and TEB-exposure rats,and then blood were collected from orbital venous plexus at predetermined time-points.The concentration of AT in plasma was detected by LC-MS/MS,and the pharmacokinetic parameters were calculated by the DAS pharmacokinetic software.An intestinal circulation perfusion model was established in normal rats,and perfused with the perfusates containing the model drug of fluorescein and the BAs with the same compositions as the normal/TEB-exposure rats.After perfusion,the absorption and permeability of fluorescein in intestine were detected,as well as the oxidative stress status and ZO-1 expression level in the intestinal tissues.Results:Compared with normal rats,TEB-exposure increased the amounts of glycocholic acid,glycochenodeoxycholic acid,taurocholic acid and taurine deoxycholic acid in intestine significantly(P<0.001).In TEB-exposure rats,the maximum plasma concentration and area under the curve of AT were increased significantly than those of normal rats(P<0.05),and the peak time was significantly delayed(P<0.05).The TEB-induced BAs homeostasis perturbance increased intestinal permeability,and this effect was associated with the elevation of oxidative stress and the down-regulation of intercellular tight junction proteins in intestinal tissues.Conclusion:TEB-exposure can affect the oral absorption behavior of AT,which is probably related with the intestinal BAs homeostasis perturbance,thus it might affect the clinical efficacy and safety of this drug.
文摘In this paper functionalized multiwall carbon nanotubes (FMWCNT) were modified using atenolol as a class of drugs that were used in cardiovascular diseases containing reactable nitrogen, which could attach chemically to functionalized MWCNT. This product was characterized by Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. These spectrums proved the existence of nitrogen atoms of amide due to new functional group. The morphology were also determined by scanning electron microscopy (SEM) and showed that this product was synthesized in the nanometer dimension. Thermal gravimetery (TGA) analysis was also used to evaluate thermal properties.
文摘The objective of the study was to evaluate the drug-drug interaction studies of levoceterizine with atenolol. Calibration curve studies of working standard solutions of levocetirizine and atenolol （0.01-0.1 mmol） were scanned. Maxima appeared at 231 nm for levocetirizine and 224 nm for atenolol. The calibration curve obeyed Beer Lambert＇s Law. Lone availabilities of both the drugs were studied in pH 1, pH 4, pH 7.4 and pH 9 at 37℃ on B.P. （British Pharmacopoeia） dissolution apparatus. To study the drug-drug interaction of levocetirizine （5 mg tablet） and atenolol （100 mg tablet）, both the drugs were introduced to the dissolution apparatus in simulated gastric juice （pH 1）, pH 4, pH 7.4 and pH 9 at 37℃ at zero time and measured the absorbance maxima of both the drugs at the corresponding wavelength. Graphs were plotted for availability percentage （%） of drug versus time at each set of experiment. The availability percentage （%） of levocetirizine in the buffers of pH simulated to gastric pH 4, pH 7.4 and pH 9 in the presence of atenolol was 436.78%, 376.90%, 436.78% and 436.78%, respectively, but the availability of atenolol was increased up to 214.80%, 212.96%, 214.93% and 231.51% in simulated to gastric pH and in the buffers ofpH 4, pH 7.4 and pH 9, respectively. On the basis of these studies, it is concluded that levocetirizine forms a charge-complex with atenolol; therefore, co-administration of these drugs should be avoided.
文摘目的:分析选择性β_(1)受体阻滞剂治疗高血压的有效性和安全性,进一步更新选择性β_(1)受体阻滞剂的循证医学证据。方法:计算机检索中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、Embase、Cochrane Library,搜集关于选择性β_(1)受体阻滞剂治疗高血压患者的随机对照试验,检索时间均为建库至2024年5月。由两名研究者独立进行文献进行筛选、提取资料并评估纳入研究的偏倚风险,采用Cochrane偏倚风险工具对纳入研究进行质量评价,采用R4.4.0软件进行网状Meta分析,计算各结局指标的累积排序概率图下面积(the surface under the cumulative ranking,SUCRA)以比较不同干预措施的有效性与安全性。结果:SUCRA值排序结果显示,在降低收缩压方面:比索洛尔(79.33%)>阿替洛尔(57.46%)>美托洛尔缓释剂(51.12%)>美托洛尔速释剂(12.08%);降低舒张压方面:压比索洛尔(77.38%)>阿替洛尔(65.63%)>美托洛尔缓释剂(51.41%)>美托洛尔速释剂(5.57%);降低24 h动态收缩压方面:比索洛尔(92.44%)>美托洛尔速释剂(54.09%)>美托洛尔缓释剂(52.47%)>阿替洛尔(1.01%);降低24 h动态舒张压方面:比索洛尔(95.24%)>美托洛尔速释剂(52.52%)>美托洛尔缓释剂(46.82%)>阿替洛尔(5.4%);降低心率幅度方面:比索洛尔(97.88%)>阿替洛尔(66.98%)>美托洛尔缓释剂(22.72%)>美托洛尔速释剂(12.42%);降低24 h动态心率方面:美托洛尔缓释剂(69.49%)>比索洛尔(54.97%)>阿替洛尔(39.39%)>美托洛尔速释剂(36.17%);不良反应发生率方面:阿替洛尔(81.38%)>美托洛尔缓释剂(54.86%)>比索洛尔(48.97%)>美托洛尔速释剂(14.79%)。结论:比索洛尔、阿替洛尔、美托洛尔速释剂和美托洛尔缓释剂治疗高血压时均有明显的有效性,其中比索洛尔的有效性最为显著,而阿替洛尔的总不良反应发生率较高,临床使用时应给予关注。
