Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin

The development of new orally dispersible tablets containing amlodipine (AML) inclusion complexes in hydroxypropyl-β-cyclodextrin (HP-β-CD) and in methyl-β-cyclodextrin (Me-β-CD) was studied. The methods of obtaining amlodipine and the physical and chemical properties of the inclusion complexes using the two cyclodextrins was investigated separately. Solid inclusion complexes were obtained by three methods: kneading, coprecipitation, and lyophilization, at a molar ratio of 1:1. For comparison, a physical mixture in the same molar ratio was prepared. The aim of the complexation process was to improve the drug solubility. As the lyophilization method leads to a complete inclusion of the drug in the guest molecule cavity, for both used cyclodextrins, these types of compounds were selected as active ingredients for the design of orally dispersible tablets. Subsequently, the formulation of the orodispersible tablets containing AML-HP-β-CD and AML-Me-β-CD inclusion complexes and quality parameters of the final formulation were evaluated. The results prove that F1 and F4 formulations, based on silicified microcrystalline cellulose, which contains insignificant proportions of very small or very large particles, had the lowest moisture degree (3.52% for F1 and 4.03% for F4). All of these demonstrate their porous structure, which led to good flowability and compressibility performances. F1 and F4 formulations were found to be better to manufacture orally dispersible tablets.     

硝苯地平控释片和赖诺普利联合治疗对高血压患者肾功能的影响

目的：探讨硝苯地平控释片、赖诺普利单独治疗和联合治疗对高血压病患者肾功能的影响。方法：72例高血压病患者随机分为3组：硝苯地平控释片组（30mg，qd，24例）；赖诺普利组（10mg，qd，24例）；硝苯地平控释片和赖诺普利联合治疗组（硝苯地平控释片30mg，qd，赖诺普利（10mg，qd，24例），疗程24周。治疗前、后观察肾功能指标变化。结果：①硝苯地平控释片、赖诺普利及联合治疗组高血压病患者治疗后均能显著降低血压（P〈0．01）及尿蛋白的排泄量。但联合治疗组降低尿蛋白排泄的幅度比硝苯地平控释片组、赖诺普利组明显高，而硝苯地平控释片组和赖诺普利组之间差异无统计学意义（P〉0．05）。②治疗后，肾小球滤过率在联合治疗及赖诺普利组明显增高，而硝苯地平控释片组无明显变化。3．三组治疗后尿蛋白下降幅度与血压下降幅度均无显著相关。结论：硝苯地平控释片、赖诺普利长期单独治疗均可减少蛋白尿。保护肾功能，两药联合治疗对减少蛋白尿、保护肾功能有一定相加作用。     

反相高效液相色谱法测定苯磺酸氨氯地平胶囊的含量和有关物质

目的建立测定苯磺酸氨氯地平胶囊中苯磺酸氨氯地平含量及有关物质的反相高效液相色谱(RP-HPLC)法。方法采用HypersilBDS柱(200 mm×4.6 mm,5μm),以0.01 mol/L磷酸氢二钾溶液(含0.7%三乙胺,磷酸调pH=4.0±0.1)-乙腈(70∶30)为流动相,流速为1.0 mL/min,柱温为30℃,检测波长237 nm。结果苯磺酸氨氯地平峰和相邻杂质峰可达到有效分离(R>1.5)。苯磺酸氨氯地平质量浓度在5.0～50.0μg/mL范围内与峰面积线性关系良好(r=0.999 9,n=5);低、中、高3种质量浓度的平均回收率分别为99.17%,100.03%,99.85%,RSD分别为1.21%,0.87%,1.06%(n=3);方法的精密度和重复性良好,RSD均小于2%。结论该方法准确、简便、快速,适用于苯磺酸氨氯地平胶囊的质量控制。     

高血压病合并心力衰竭时使用硝苯地平、氨氯地平治疗的对比观察

目的　观察高血压病合并心衰时使用硝苯地平、氨氯地平治疗时对心脏影响。　方法　 4 7例高血压病合并心衰患者 ,分为硝苯地平治疗组 (30 mg/d,n=2 5 )及氨氯地平 (5 m g/d,n=2 2 )治疗组。观测 2 4 h平均血压、平均心率 ,脉压 ,左室射血分数 (L VEF)、舒张早期减速度 (Dct)、左室等容舒张时间 (IVRT)。　结果　血压、心率、L VEF两组差异不显著 (P>0 .0 5 ) ;平均脉压、IVRT硝苯地平组大于氨氯地平组 (P<0 .0 1) ;硝苯地平组 Dct小于氨氯地平组 (P<0 .0 1)。　结论　高血压合并心衰时使用硝苯地平增大脉压差 ,并影响心脏的舒张功能。     

动态血压监测评价甲磺酸氨氯地平的降压疗效

目的:应用动态血压监测(ABPM)评价甲磺酸氨氯地平的降压疗效,并与苯磺酸氨氯地平进行比较。方法:77例高血压患者按不同的治疗药物随机分为甲磺酸氨氯地平组、苯磺酸氨氯地平组,均治疗12周,治疗前后测定动态血压、心率、诊室血压、生化指标。结果:治疗12周末,2组的诊室血压,24h、白昼及夜间平均血压、平均脉压、血压负荷均显著降低(P<0·05或P<0·01),心率无显著改变。12周末甲磺酸氨氯地平组的总有效率在诊室血压为92·3%,在ABPM为71·8%;苯磺酸氨氯地平组分别为92·1%和68·4%,2组间均差异无统计学意义。甲磺酸氨氯地平组收缩压和舒张压的24h降压谷/峰比分别为70%和72%;苯磺酸氨氯地平组分别为66%和69%。2组患者出现的不良反应均轻微。结论:甲磺酸氨氯地平与苯磺酸氨氯地平一样能平稳、有效、安全地降低血压,可作为一线降压用药。     

果糖对全麻患者顺苯磺阿曲库铵肌松效果的影响

目的探讨果糖对全麻患者顺苯磺阿曲库铵肌松效果的影响。方法ASAI～II级、择期全麻下行体表手术患者40例,年龄18～65岁,随机分为对照组（c组）和果糖组（F组）（n=2O）。麻醉诱导前30min内F组静滴10％果糖注射液2．5ml／kg,C组静滴生理盐水2．5ml／kg。丙泊酚、芬太尼麻醉诱导后,注入2倍ED95（0．1mg／kg）顺苯磺阿曲库铵。麻醉维持：七氟烷和瑞芬太尼。肌松监测用刺激尺神经拇内收肌四个成串刺激（TOF）,记录肌松起效时间和临床有效时间及麻醉诱导前、诱导后30min、60min、90min的食道温度T0、T30、T60、T90结果食道温度：二组间比较,T0差异无统计学意义,F组T60、T90明显高于C组（P〈0．05）。组内比较,与T0相比,二组T30、T60、T90均明显降低（P〈0．05）。肌松效果：二组肌松起效时间差异无统计学意义,F组临床有效时间明显短于c组（P〈0．05）。结论麻醉前输注果糖可缩短顺苯磺阿曲库铵肌松临床有效时间,但不影响其起效时间。其原因可能与果糖减缓全麻时体温下降有关。     

氨氯地平联合阿伐他汀治疗高血压合并高血脂症疗效观察

目的探讨高血压合并高血脂症患者给予氨氯地平联合阿伐他汀治疗效果。方法选取2010年1月~2011年12月间收治的100例高血压合并高血脂症患者为研究对象,将其按照随机数字法分为对照组和研究组,对照组给予常规的氨氯地平治疗,研究组给予氨氯地平联合阿伐他汀治疗,观察两组的临床治疗效果。结果通过对两组的治疗效果比较,研究组的总有效率为94.0%,对照组的总有效率为72.0%,研究组的临床治疗总有效率明显优于对照组,差异有统计学意义(P0.05)。治疗前后对照组和研究组的SBP和DBP比较差异无统计学意义(P0.05);治疗后研究组和对照组的SBP和DBP较治疗前均有明显的改善,且组间的数据比较差异有统计学意义(P0.05)。治疗前研究组和对照组的LDL-C、HDL-C、TG和TC比较差异无统计学意义(P0.05);治疗后研究组和对照组的LDL-C、HDL-C、TG和TC较治疗前均有明显的改善,且组间的数据比较差异有统计学意义(P0.05)。对照组不良反应发生率为12.0%,研究组不良反应发生率为16.0%,两组的数据比较差异无统计学意义(P0.05)。结论高血压合并高血脂症患者给予氨氯地平联合阿伐他汀治疗效果显著,治疗安全性高,值得临床应用与推广。     

辛伐他汀对高血压患者血压及左心室结构的影响

目的 观察辛伐他汀对社区原发性高血压患者血压及左心室结构的影响,提高社区原发性高血压治疗效果及改善预后.方法 将280例符合入组标准的原发性高血压患者按随机数字表分为观察组140例和对照组140例,对照组给予氨氯地平治疗,5 mg/次,1次/d,观察组在对照组基础上再口服辛伐他汀治疗,20mg/次,1次/d,2组均治疗8周,治疗前后观察血压变化情况,检查血脂水平变化情况,并采用超声心动图检查评价心肌肥厚程度,记录不良反应发生情况.结果 ①观察组和对照组总有效率分别为95.00％、83.57％,差异具有统计学意义,x2 =16.311,P＜0.01;②观察组与对照组治疗前SBP、DBP、TC、TG、IVST、LVPWT、LVDd差异没有统计学意义,具有可比性,观察组与对照组治疗后SBP、DBP、TC、TG、IVST、LVPWT、LVDd分别为（131 ＆#177;4） mm Hg vs.（139＆#177;5） mmHg,（78＆#177;6） mm Hg vs.（91 ＆#177;6） mm Hg,（4.02＆#177;0.95） mmol/L vs.（5.24＆#177;1.05） mmol/L,（1.05＆#177;0.86） mmol/L vs.（1.55＆#177;1.00） mmol/L,（9.3＆#177; 1.6） mm vs.（11.1＆#177;1.8）mm,（10.0＆#177;1.5） mm vs.（11.9＆#177;1.7） mm,（44.4＆#177;2.2） mmvs.（49.3＆#177;3.3） mm,各个指标差异具有统计学意义,均P＜0.05（1mm Hg =0.133 kPa）.结论 辛伐他汀联合氨氯地平能协同降低血压及逆转左室肥厚,降低靶器官损伤,改善预后,效果优于单纯氨氯地平治疗,值得临床推广使用.     

高血压合并冠心病患者临床应用氨氯地平、阿托伐他汀联合治疗的血脂调节效果研究

目的：探讨氨氯地平阿托伐他汀片治疗高血压合并冠心病患者,对其血脂调节的临床影响。方法方便选择2012年5月―2015年12月该院收治的高血压合并冠心病患者110例,按照随机数字表法分为两组,各55例,对照组使用阿托伐他汀,观察组使用氨氯地平阿托伐他汀钙片,连续治疗8周为1疗程,比较两组血脂变化情况,并统计两组临床治疗效果。结果干预后观察组总胆固醇为(3.1±0.2﹚mmol/L,显著低于对照组的(4.5±0.5﹚mmol/L(P<0.05﹚,甘油三酯为(1.8±0.2﹚mmol/L,显著低于对照组的(2.4±0.3﹚mmol/L(P<0.05﹚,低密度脂蛋白为(1.9±0.1﹚mmol/L,显著低于对照组的(2.3±0.2﹚mmol/L(P<0.05﹚,观察组有效率为96.4%,对照组有效率为81.8%,观察组有效率显著高于对照组(P<0.05﹚,差异均有统计学意义。结论氨氯地平、阿托伐他汀联合治疗高血压合并冠心病患者,能有效调节患者血脂代谢,提高临床治疗效果。     

SELF-MEASURED SYSTOLIC BLOOD PRESSURE IN THE MORNING IS A STRONG INDICATOR OF DECLINE OF RENAL FUNCTION IN HYPERTENSIVE PATIENTS WITH NON-DIABETIC CHRONIC RENAL INSUFFICIENCY

While blood pressure is a recognized major determinant of renal function deterioration, the role of self blood pressure measurement (BPM) in predicting the loss of renal function in hypertensive patients with chronic renal insufficiency (CRI) has not been adequately addressed. One hundred and thirteen patients (F/M: 46/67; 56±1 years) with CRI (mean serum creatinine: 1.87±0.08; range: 1.4 to 3.5?mg/dl; average urinary protein excretion: 1.2±0.2?g/24?hrs.) were followed for 3 years. The record of renal biopsy revealed that 74 patients had IgA nephropathy, 16 had chronic glomerulonephritis, and 6 had membranous nephropathy, while 17, unbiopsied patients had underlying renal disease of unknown origin. Self BPM were made at regular intervals throughout the course of the study. All recorded blood pressures were included in a stepwise multiple regression analysis in which the decline in GFR per year was the dependent variable. Patients were primarily treated with a combination of amlodipine (5 to 20?mg daily), a calcium antagonist, and benazepril(2.5 to 5?mg daily), an ACE inhibitor in an effort to reduce their blood pressure at the office to <130/85?mmHg. The simple correlation between blood pressures (i.e., office, home morning and home evening) and the decline in GFR were all statistically significant. The correlation coefficients of determination for this model were as follows: r=0.64 for home morning SBP; 0.43 for office SBP; 0.39 for office DBP; and 0.38 for home morning DBP. The level of urinary protein excretion did not correlate with the decline in GFR. These data suggest that self BPM improves prognostic ability in hypertensive patients with CRI.