Co-amorphous solid dispersion systems of lacidipine-spironolactone with improved dissolution rate and enhanced physical stability

Co-amorphous solid dispersion(C-ASD)systems have attracted great attention to improve the solubility of poorly soluble drugs,but the selection of an appropriate stabilizer to stabilize amorphous forms is still a huge challenge.Herein,C-ASD system of two clinical combined used drugs(lacidipine(LCDP)and spironolactone(SPL))as stabilizers to each other,was prepared by solvent evaporation method.The effects of variation in molar ratio of LCDP and SPL(3:1,1:1,1:3,1:6,and 1:9)on the drug release characteristics were explored.Polarized light microscopy(PLM),powder X-ray diffraction(PXRD),differential scanning calorimetry(DSC)and thermogravimetric analysis(TGA)were employed to evaluate the solid states.Prepared C-ASDs were further studied for their stability under the high humidity(RH 92.5%).Further analysis of C-ASDs via Fourier-transform infrared spectroscopy(FTIR)and Raman spectroscopy confirmed that hydrogen bond interactions between the two drugs played a significant role in maintaining the stability of the C-ASDs systems.Moreover,molecular dynamic(MD)simulations provided a clear insight into the stability mechanism at the molecular level.This study demonstrated the novel drug-drug C-ASDs systems is a promising formulation strategy for improved dissolution rate and enhanced physical stability of poorly soluble drugs.

Effect of spironolactone on cardiac remodeling after acute myocardial infarction

BACKGROUND:Few studies have reported the effect of aldosterone receptor antagonist(ARA) on myocardial remodeling after acute myocardial infarction(AMI).This study was undertaken to investigate the preventive effect of ARA on myocardial remodeling after AMI.METHODS:A total of 616 patients who had been admitted into the CCU of the First Affiliated Hospital of Harbin Medical University from January 2008 to January 2010 were studied prospectively.Only 528 patients were observed completely,including 266 of the control group and 262 of the treatment group.There was no statistical difference in age,gender,medical history,admission situation,and treatment between the two groups(P>0.05).The preventive effects of spironolactone on cardiac remodeling,left ventricular function,renal function and blood levels of potassium were evaluated by echocardiography,serum potassium and serum creatinine at one-month and one-year follow-up.RESULTS:The echocardiography indicators such as LVESD,LVEDD,LVEF,LAD-ML and LADSI were significantly improved in the treatment group compared with the control group at one year(P<0.05).In the treatment group,LVESD,LVEDD,LVPWT,LVEF,LAD-ML and LAD-SI were more significantly improved at one year than one month(P<0.05,P=0.007 to LVEF),and in the control group LVEF was more significantly improved at one year than one month(P=0.0277).There were no significant differences in serum potassium and serum creatinine levels between the two groups.CONCLUSION:On the basis of conventional treatment,the early combination of low-dose spironolactone(20 mg/d) could inhibit cardiac remodeling at late stage and prevent heart fadure.

Clinical research of fenofibrate and spironolactone for acute central serous chorioretinopathy

AIM：To compare the effectiveness of combined fenofibrate and spironolactone with fenofibrate alone for treatment of central serous chorioretinopathy（CSCR）.METHODS： Totally 60 patients（60 eyes） with a history of acute CSCR were randomed into two groups： group A with combination of fenofibrate（200 mg） and spironolactone（100 mg）,and group B with only fenofibrate（200 mg）.They were taken half an hour before meals and once per day for 8wk.The changes of the visual acuity,subjective symptom,ocular surface disease index（OSDI）,the tear film and optical coherence tomography were observed at 2,4,6,and 8wk before and after treatment.RESULTS： The best corrected visual acuity（BCVA,log MAR） was improved to 0.22 and 0.27 after treatment from baseline of 0.35 and 0.36 in groups A and B（P 〈0.05）,respectively.After 8wk treatment,the central subfield thickness（CST）,and subretinal fluid volumn（SFV） decreased significantly to 49.5% and 78.8% in group A,37.0% and 57.2% in group B.There were significant differences of CST and SFV in both groups（all P 〈0.05）.CONCLUSION：Fenofibratecombinedwithspironolactone may have more clinical efficacy in the treatment of CSCR than fenofibrate only.

Study the Effect of Spironolactone in Airway Resistance with Impulse Oscillometry in Patients with Congestive Heart Failure

Background: CHF (Congestive Heart Failure) is one of the most important causes of mortality and morbidity in the world. Diuretics such as spironolactone can decrease pulmonary congestion and reduce the amount of fibrosis in CHF patients. The goal was to assess whether spironolactone can decrease air way resistance and can we follow up the effect of diuretic therapy in patients of heart failure quantitatively by means of impulse oscillometry. Methods: It was clinical trial which performed in Ahvaz teaching hospital. 24 patients with congestive heart failure (CHF) which was classified as functional class II-IV and had EF Result: The age of patient was 61 ± 10 and the age of control was 57 ± 7 years old. The data of oscillometry before and after spironolactone were X5 (&minus;0.14 ± 0.05 vs &minus;0.14 ± 0.05, P: 0.93), R5 (0.39 ± 0.21 vs 0.39 ± 0.15, P: 0.35), X20 (&minus;0.04 ± 0.06 vs &minus;0.06 ± 0.06, P: 0.37), R20 (0.04 ± 0.03 vs 0.06 ± 0.06, P: 0.37), Zrs (0.39 ± 0.21 vs 0.39 ± 0.15, P: 0.35). Conclusion: There was a trend toward reduction of peripheral airway resistances in CHF patients than controls with use of 1 month of spironolactone. Although there was not significant change in the number of X5, R5, X20, R20 occurred the trend toward reduction of number triggers the point that oscillometry can be used for quantitative follow up of CHF patients.

Application Effect Evaluation of Telmisartan combined with Spironolactone after Catheter Ablation of Patients with Paroxysmal Atrial Fibrillation

Objective:To evaluate the application effect of telmisartan combined with spironolactone after catheter ablation of patients with paroxysmal atrial fibrillation.Methods:80 cases of patients with paroxysmal atrial fibrillation who received radiofrequency catheter ablation treatment from March 2013 to March 2016 in our hospital were randomly selected,these patients were divided into two groups according to the treatment methods,namely,the telmisartan with Spironolactone treatment group(combined treatment group,n=40)and the conventional therapy group(n=40).The hs-CRP,NT-proBNP,LAD and recurrence of the two groups were analyzed.Results:The hs-CRP,NT-proBNP levels after 3 months of the combined treatment group were significantly lower(P<0.05),the recurrence rate 10.0%(4/40)was significantly lower than the conventional therapy group 27.5%(11/40)(P<0.05),the time to recurrence was significantly longer than the conventional therapy group(P<0.05).Conclusion:The application effects of telmisartan combined with spironolactone after catheter ablation in the treatment of patients with paroxysmal atrial fibrillation are better than conventional therapy.

Dapagliflozin and Spironolactone Improved Clinical Symptoms and CV Outcomes in Patient with HF Preserved Ejection Fraction (HFpEF) in Hard-to-Reach Rural African Population: A Case Series

Objective: To observe the benefit of mineralocorticoid receptor antagonist and sodium-glucose co-transport 2 inhibitor (SGLT2 inhibitor) in heart failure preserved ejection (HFpEF) in rural Tanzania. Background and Result: The use of spironolactone and dapagliflozin was shown to be effective in improving the clinical outcome and reducing CV hospitalization rate and CV mortality in patients with heart failure preserved left ventricular ejection fraction (HFpEF). This is the case presentation of one patient with HFpEF with diastolic dysfunction grade 3, obesity grade 3, Type 2 Diabetes, and Atrial Fibrillation (permanent). In the case of a 76-year-old female after previous ineffective treatment, the initiation of Spironolactone and Dapagliflozin led to a rapid and marked improvement in the clinical conditions. Diastolic dysfunction was improved from stage III to stage I. Moreover, the initiation of spironolactone and dapagliflozin therapy avoided a referral for surgical intervention and interrupted a long series of hospitalizations for acute HF and prevented CV death. Conclusion: Based on our experience, we conclude that the treatment with spironolactone and dapagliflozin allows for better treatment optimization with a positive impact on the control of clinical outcomes and preventing CV death and CV hospitalization in HFpEF and related comorbidities in the African population, which is underrepresented in most of the trials.

The Effect of Spironolactone Loading on the Properties of 3D-Printed Polycaprolactone/Gold Nanoparticles Composite Scaffolds for Myocardial Tissue Engineering

Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of drugs.In this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the samples.Furthermore,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were evaluated.The microstructural observation of the scaffolds reported interconnected pores with 150–300µm in diameter.The 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D scaffolds.SPL release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th day.In addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved significantly.These findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.

Hemodynamic effects of propranolol with spironolactone in patients with variceal bleeds: A randomized controlled trial

AIM: To study the hemodynamic effects of spironolactone with propranolol vs propranolol alone in the secondary prophylaxis of variceal bleeding. METHODS: Thirty-five cirrhotics with variceal bleeding randomly received propranolol (n = 17: Group A) or spironolactone plus propranolol (n = 18: Group B). Hemodynamic assessment was performed at baseline and on the eighth day. RESULTS: Spironolactone with propranolol caused a greater reduction in the hepatic venous pressure gradient than propranolol alone (26.94% vs 10.2%; P < 0.01). Fourteen out of eighteen patients on the combination treatment had a reduction in hepatic venous pressure gradient to ≤ 12 mmHg or a 20% reduction from baseline in contrast to only six out of seventeen (6/17) on propranolol alone (P < 0.05). CONCLUSION: Spironolactone with propranolol results in a better response with a greater reduction in hepatic venous pressure gradient in the secondary prophylaxis of variceal bleeding. A greater number of patients may be protected by this combination therapy than by propranolol alone. Hence, this combination may be recommended for secondary prophylaxis in patients with variceal bleeding.

辨证分型治疗原发性肾病综合征随机平行对照研究

[目的]观察辨证分型治疗原发性肾病综合征疗效。[方法]使用随机平行对照方法,将120例门诊患者按就诊顺序号法简单随机分为两组。对照组60例泼尼松,1mg/kg,1次/d;氢氧噻嗪,25mg/次,2次/d;螺内酯,20mg/次,2次/d;双嘧达莫,50mg/次,3次/d;血脂康,0.6g/次,2次/d。治疗组60例辨证分型,脾肾阳虚:参芪真武汤(党参、白术、附片制、巴戟天、仙灵牌、补骨脂各15g,黄芪、茯苓、芡实各30g,白芍、生姜、干姜各10g);脾气虚并肾阳虚:六君子汤加温肾助阳药(党参、白术、巴戟天、仙灵牌、菟丝子、补骨脂各15g,茯苓、黄芪、芡实各30g,甘草炙、陈皮各6g,三仙焦、法半夏各10g);脾气虚并肾阴虚:参苓白术散加滋肾益阴药(党参、白术、扁豆炒、莲子、桑椹、生地各15g,茯苓、生薏仁、黄芪、芡实各30g,生山药、女贞各20g,桔梗10g,砂仁6g);脾气不升并肾精亏虚:补中益气汤合益肾固精方(党参、白术、巴戟天、覆盆子、菟丝子、枸杞、黑豆各15g,黄芪、芡实各30g,升麻、柴胡、陈皮各6g,甘草炙、当归各10g);均1剂/d,水煎400m L,早晚口服。连续治疗30d为1疗程。观测临床症状、尿蛋白、尿红细胞、尿沉渣、血清蛋白、甘油三酯、总胆固醇、反跳率、不良反应。治疗1疗程,判定疗效。[结果]治疗组痊愈37例,显效6例,有效8例,无效8例,总有效率86.67%。对照组痊愈19例,显效7例,有效13例,无效21例,总有效率65.00%。治疗组疗效优于对照组(P<0.01)。反跳率治疗组改善优于对照组(P<0.01)。[结论]辨证分型治疗原发性肾病综合征疗效满意,无严重不良反应,值得推广。

阳离子表面活性剂敏化的极谱催化波法测定螺内酯

目的:建立螺内酯含量测定的新方法。方法:应用阳离子表面活性剂CTMAB增敏的极谱催化波法。结果:在包含1 0 0mmol/LKIO3和8 0×1 0 - 8mol/LCTMAB的B -R缓冲液(pH =9 0 )条件下,螺内酯一阶导数峰高与其浓度在0 . 0 1～6 . 0 0 μmol/L范围内成线性,线性方程为Y =1 0 . 37(mm) +6 5 . 9X (r=0 .9997)。日内催化波峰高的精密度为2 . 6 %,平均回收率为1 0 1 3%。结论:该方法灵敏度高,操作简便,准确度好,可用于螺内酯片剂中螺内酯含量的测定。

螺内酯对射血分数轻度降低心力衰竭合并2型糖尿病患者的临床疗效观察及预后研究

目的 探究螺内酯对射血分数轻度降低的心力衰竭合并2型糖尿病患者的临床疗效及预后观察。方法 纳入2019年2月至2022年12月于北京朝阳医院治疗的射血分数轻度降低的心力衰竭合并2型糖尿病患者共409例。所有患者在试验前均未服用过螺内酯,已接受其他心衰标准药物治疗及降糖药物治疗至少半年。通过随机分组将纳入患者分为试验组及对照组,试验组在对照组治疗基础上加用螺内酯10~20 mg/d。比较两组患者治疗前后的糖化血红蛋白(glycated hemoglobin, HbA1c)、体质量指数、血浆N末端B型利钠肽原(NT-proBNP)、左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、舒张期二尖瓣峰值流速与二尖瓣环舒张早期运动峰速度的比值(E/e’)、血清肌酐(Scr)、血清尿酸(SUA)、肌酐清除率(Ccr)、血钾水平等指标的变化,观察治疗相关不良反应、心血管死亡或心衰恶化再住院复合终点事件发生率,评估临床治疗效果。结果 两组患者于治疗前的一般资料比较差异无统计学意义(P>0.05);治疗后试验组患者的HbA1c水平较对照组下降[(7.2±0.5)vs.(7.9±0.7),P<0.05],NT-proBNP水平较对照组降低[(423±155)vs.(640±157),P<0.05];试验组治疗后的心功能及肾功能多项指标的改善情况优于对照组(均P<0.05),心功能Ⅱ~Ⅳ级的试验组患者于治疗期间血钾水平相对稳定(均P>0.05)。治疗后试验组的临床显效率及总有效率高于对照组(均P<0.05),复合终点事件发生率及药物治疗相关不良反应在两组中差异无统计学意义(均P>0.05)。结论 螺内酯有助于射血分数轻度降低的心力衰竭合并2型糖尿病患者的血糖管理,并能进一步改善心脏功能及肾功能,同时具有良好的药物使用安全性。

Analysis of spironolactone residues in industrial wastewater and in drug formulations by cathodic stripping voltammetry

The redox behavior of spironolactone（SP） drug in Britton-Robinson（BR） buffer of pH 2-11 was investigated by differential pulse cathodic stripping voltammetry（DPCSV） and cyclic voltammetry（CV） at hanging mercury dropping electrode（HMDE）.At pH 9-10.5,the DPCSV of SP drug showed two cathodic peaks at1.15 and1.38 V at the HMDE vs.Ag/AgCl reference electrode.In the CV,at pH 9-10,the dependence of the cathodic peak current,Ip,c and peak potential,Ep,c of the second peak（Ep,c2） on the scan rate（n） and on the depolizer（SP） concentrations was typical of an electrode coupled（EC） chemical reaction type mechanism.The plot of Ip,cat 1.380 V of the DPCSV vs.SP concentration at pH 9 was linear over the concentration range of 1.2×1010-9.6×107 M.The lower limit of detection（LLOD） and limit of quantification（LOQ） of the drug were 1.1×1011 and 4.14×1011 M,respectively.The method was successfully applied for the analysis of SP residues in industrial wastewater,in pure form（98.273.1%） and in drug formulations e.g.Aldactones tablet（98.3572.9%）.The method was validated by comparison with HPLC and the official data methods.

益气活血汤联合西药治疗充血性心力衰竭随机平行对照研究

[目的]观察益气活血汤联合西药治疗充血性心力衰竭疗效。[方法]使用随机平行对照方法,将80例住院患者按病志号抽签法简单随机分为两组。对照组40例休息,限制水、钠摄入及抗感染治疗;托拉塞米,20mg/次,1次/d;螺内酯,20mg/次,4次/d;雷米普利,2.5mg/次,1次/d;单硝酸异山梨酯,20mg/次,3次/d;美托洛尔,25mg/次,2次/d。治疗组40例益气活血汤(黄芪20g,人参先煎10g,山药、白术各15g,山茱萸、降香、五加皮各10g,三七6g,丹参12g),1剂/d,水煎600m L,早晚口服,300m L/次;西药治疗同对照组。连续治疗14d为1疗程。观测临床症状、LVSD、LVDD、LVEF、HR、CO、血浆BNP水平、不良反应。治疗1疗程,判定疗效。[结果]治疗组显效28例,有效10例,无效2例,总有效率95.00%。对照组显效18例,有效13例,无效9例,总有效率77.50%。治疗组疗效优于对照组(P<0.05)。相关指标两组均有改善(P<0.01),治疗组改善优于对照组(P<0.05)。[结论]益气活血汤联合西药治疗充血性心力衰竭疗效满意,无严重不良反应,值得推广。

心痹汤联合西药治疗冠心病慢性心力衰竭(气虚血瘀水停)随机平行对照研究

[目的]观察心痹汤联合西药治疗冠心病慢性心力衰竭(气虚血瘀水停)疗效。[方法]使用随机平行对照方法,将82例门诊患者按就诊顺序号方法随机分为两组。对照组41例阿司匹林,100mg/次,1次/d;阿托伐他汀钙,10mg/次,1次/d;单硝酸异山梨酯,10~20mg/次,2次/d;呋塞米,最大剂量≤100mg/次,1次/d;螺内酯,20mg/次,1次/d;地高辛,0.125~0.5mg/次,1次/d;美托洛尔,6.25~25mg/次,2次/d;贝那普利,2.5~5mg/次,1~2次/d,血压偏低者酌减降压药物剂量。治疗组41例心痹汤(白术炒、黄芪生、党参、茯苓各15g,红花、丹参、桃仁、当归尾各9g,甘草炙10g),水煎400m L,药汁送服水蛭粉1.5g,1剂/d,2次/d,早晚温服;西药治疗同对照组。连续治疗4周为1疗程。观测临床症状、左心室射血分数(LVEF)、6min步行距离、不良反应。治疗1疗程(4周),判定疗效。[结果]治疗组显效21例,有效16例,无效4例,总有效率90.20%;对照组显效15例,有效13例,无效13例,总有效率68.33%;治疗组疗效优于对照组(P<0.05)。LVEF、6min步行距离两组均有改善(P<0.01),治疗组改善优于对照组(P<0.01)。[结论]心痹汤联合西药治疗冠心病慢性心力衰竭(气虚血瘀水停),疗效满意,无严重不良反应,值得推广。

螺内酯对实验大鼠肝组织TGFβ1、PDGF-BB及α-SMA表达的影响

目的 探讨螺内酯预防肝纤维化的作用机制。方法 SD大鼠 90只 ,随机分为 3组。正常对照组 (8只 ) :正常饮食 ,皮下注射花生油 ;模型组 (42只 ) :复合因素制成肝纤维化模型 ;螺内酯预防组 (40只 ) :造模方法同模型组 ,螺内酯 10 0mg·kg- 1·d- 1灌胃。分别于第 2周、4周、6周、8周末随机处死 8只大鼠 ,取肝组织用免疫组化法检测各组肝组织内转化生长因子 β1(TGFβ1)、血小板衍生生长因子 (PDGF BB)及α 平滑肌动蛋白 (α SMA)含量。结果 螺内酯预防组TGFβ1、PDGF BB及α SMA在肝组织中的表达均较模型组明显减少 (P <0 .0 5或P <0 .0 1)。 结论 螺内酯可通过降低TGFβ1、PDGF

心康胶囊联合西药治疗慢性收缩性心力衰竭随机平行对照研究

[目的]观察心康胶囊联合西药治疗慢性收缩性心力衰竭疗效。[方法]使用随机平行对照方法,将60例住院及门诊患者简单随机分为两组。对照组30例呋塞米40mg/d,螺内酯20mg/d,依那普利5mg/d,美托洛尔12.5mg/d,地高辛0.125mg/d,常规抗心衰治疗。治疗组30例心康胶囊,3粒/次,3次/d,口服;西药治疗同对照组。连续治疗2周为1疗程。观测临床症状、射血分数(EF)、脑利钠肽(BNP)、不良反应。连续治疗2疗程(4周),判定疗效。[结果]EF、BNP两组均有改善(P<0.01),治疗组改善优于对照组(P<0.01)。[结论]心康胶囊联合常规抗心力衰竭药物可提高慢性收缩性心力衰竭疗效。

葶苈真武汤联合西药治疗充血性心力衰竭随机平行对照研究

[目的]观察葶苈真武汤联合西药治疗充血性心力衰竭疗效。[方法]使用随机平行对照方法,将120例住院患者按病志号抽签法简单随机分为两组。对照组60例利尿剂:双氢克尿噻,25mg/次,1~3次/d;螺内酯,20mg/次,1~2次/d;或呋塞米(Ⅲ级、Ⅳ级),20mg/次,1~3次/d。血管紧张素转化酶抑制剂卡托普利,12.5mg^25mg/次,1~3次/d。洋地黄类(Ⅲ级、Ⅳ级):地高辛,0.125mg/次,1次/d;根据情况西地兰0.2~0.4mg+5%葡萄糖250m L,静注。血管扩张剂:硝酸异山梨酯,10mg/次,3次/d;根据情况联合硝酸甘油,5~10mg/次,1次/d,共注射1~5d。吸氧:间断吸氧,3-4L/h,根据情况吸氧,3-4L/h;注意电解质,必要时补钾;注意24h尿量治疗。治疗组60例葶苈真武汤(葶苈子30g,附片先煎30min、红参各15g,黄芪30g,白术、茯苓各15g,丹参12g;咳嗽甚加紫菀、杏仁各10g;喘甚加苏子、五味子各10g;心悸加龙骨、牡蛎各20g;瘀血重加桃仁15g,红花12g;浮肿重加车前子、泽泻各10g);1剂/d,水煎300m L,早中晚口服,100m L/次;西药治疗同对照组。连续治疗14d为1疗程。观测指临床症状、BNP、不良反应。治疗1疗程,判定疗效。[结果]治疗组显效32例,有效27例,无效1例,死亡0例,总有效率98.33%。对照组显效20例,有效26例,无效12例,死亡2例,总有效率76.67%。治疗组疗效优于对照组(P<0.01)。脑钠肽值两组均有改善(P<0.01),治疗组改善优于对照组(P<0.01)。[结论]葶苈真武汤联合西药治疗充血性心力衰竭疗效满意,无严重不良反应,值得推广。

沙库巴曲缬沙坦联合螺内酯等对老年射血分数降低的心力衰竭患者心功能的影响

目的探讨沙库巴曲缬沙坦联合螺内酯、酒石酸美托洛尔治疗老年射血分数降低的心力衰竭(heart failure with reduced ejection fraction,HFrEF)的疗效及对患者心功能及血清N末端脑钠肽前体(N-terminal probrain natriuretic peptide,NT-proBNP)水平的影响。方法选取收治的120例老年HFrEF患者作为研究对象,用随机数字表法分为对照组(60例)和观察组(60例)。2组均给予常规治疗,对照组给予螺内酯片联合酒石酸美托洛尔片,观察组在对照组治疗的基础上给予沙库巴曲缬沙坦钠片。2组均持续治疗2个月。比较治疗2个月后的临床疗效,治疗前、治疗2个月后的6 min步行试验距离(6-minute walk test,6MWT)、尿量、心肌评估参数、NT-proBNP、醛固酮和血肌酐水平,治疗期间的再入院率及不良反应。结果治疗2个月后,观察组的总有效率(91.67%)高于对照组(76.67%),P<0.05。与治疗前比较,2组6MWT、尿量、左室射血分数(left ventricular ejection fractions,LVEF)、每分钟心排血量(cardiac output,CO)和心排血指数(cardiac output index,CI)均升高,且观察组高于对照组;2组的心率(heart rate,HR)、血清NT-proBNP和醛固酮水平均降低,且观察组低于对照组(P<0.05)。治疗期间,观察组的再入院率(13.33%)低于对照组(30.00%),P<0.05;观察组不良反应发生率(13.33%)与对照组(15.00%)比较差异无统计学意义。结论沙库巴曲缬沙坦联合螺内酯、酒石酸美托洛尔能有效改善老年HFrEF患者心功能及血清NT-proBNP水平,提高患者6MWT,降低患者的再入院率,安全性良好。

沙库巴曲缬沙坦联合螺内酯治疗慢性射血分数降低的心力衰竭临床价值研究

目的:探讨沙库巴曲缬沙坦联合螺内酯治疗慢性射血分数降低的心力衰竭(HFrEF)的临床价值。方法:选取HFrEF患者98例,根据随机数字表法将患者分为血管紧张素Ⅱ受体阻滞剂(ARB)组和血管紧张素受体脑啡肽酶抑制剂(ARNI)组,各49例。两组均给予常规抗心衰及螺内酯治疗,ARB组给予缬沙坦口服,ARNI组给予沙库巴曲缬沙坦口服。比较两组临床疗效、心室重构指标[左室舒张末径(LVEDD)、左室后壁厚度(LVPW)、左室射血分数(LVEF)、室间隔厚度(IVST)和左室收缩末径(LVESD)]、血生化指标[N末端B型利钠肽原(NT-proBNP)、心肌钙蛋白I(cTnI)、肌红蛋白(Myo)、肌酸激酶同工酶(CK-MB)]、运动耐力(6 min步行试验)和心肺运动试验指标[峰值氧耗量(Peak VO_(2))、无氧代谢阈值时氧耗量(AT)、二氧化碳通气当量(VE/VCO_(2))]。统计两组治疗期间不良反应及随访1年内心血管不良事件(MACE)发生情况。结果:ARNI组总有效率高于ARB组(P<0.05)。治疗后,两组LVEDD、LVESD、IVST、LVPW较治疗前下降,且ARNI组低于ARB组;LVEF较治疗前增加,且ARNI组高于ARB组(均P<0.05)。治疗后ARNI组NT-proBNP、cTnI、CK-MB低于ARB组(均P<0.05)。治疗后,两组6 min步行距离、Peak VO_(2)、AT较治疗前增加,且ARNI组高于ARB组;VE/VCO_(2)较治疗前下降,且ARNI组低于ARB组(均P<0.05)。两组治疗期间不良反应总发生率及1年内MACE总发生率比较差异无统计学意义(均P>0.05)。结论:沙库巴曲缬沙坦联合螺内酯对慢性HFrEF患者疗效显著,能够改善心功能,逆转心室重构,降低心肺负荷,减轻心肌损伤,提高运动耐力,且安全性较好。

LC-MS/MS检测降压类中药制剂中非法添加的9种化学药物

目的建立快速、准确、灵敏的检测降压类中药制剂中非法添加盐酸肼屈嗪、阿替洛尔、氨苯蝶啶、卡托普利、盐酸哌唑嗪、盐酸普萘洛尔、氯沙坦钾、利血平和螺内酯等9种化学药物的LC-MS/MS方法。方法采用KINETEX 2.6 C18100A（50.0×2.10mm）色谱柱,梯度洗脱：流动相A为乙腈-甲醇（4∶1）,流动相B为5mmol.L-1甲酸铵缓冲液（用甲酸调节pH至3.0）,流速为0.3mL.min-1,检测波长为230、272nm,柱温为50℃;离子源为ESI源,雾化气压力为40psi,干燥气流速为12L.min-1,干燥气温度为325℃,毛细管电压为3.5kV,正离子检测模式。通过与对照品的色谱和质谱行为比较,对样品中是否添加该9种化学药物进行定性鉴别。结果上述色谱-质谱条件下,9种化学药物的检出限为0.2~2ng,符合鉴别要求。结论该方法的专属性较强、灵敏度较高,适用于降压类中药制剂中添加该9种化学药物的定性分析。