地尔硫卓的合成

重点介绍了地尔硫的化学合成和拆分方法，以及近年来在其不对称合成领域的进展。     

地奥心血康胶囊治疗急性心肌梗死

目的：探索地奥心血康（ＤＡＸＸＫ）对急性心肌梗死（ＡＭＩ）的疗效。方法：ＡＭＩ病人８９例，采用随机单盲法分为２组，ＤＡＸＸＫ胶囊组４５例，男性３６例，女性９例，年龄５９±ｓ８ａ．采用ＤＡＸＸＫ２００ｍｇ，ｐｏ，ｔｉｄ，共４ｗｋ。地尔硫组４４例，男性３４例，女性１０例，年龄５８±７ａ．采用盐酸地尔硫３０ｍｇ，ｐｏ，ｔｉｄ，共４ｗｋ。结果：ＤＡＸＸＫ组治疗后心绞痛发作频率须静脉滴注硝酸甘油的量及镇痛药需用次数均显著低于对照组；心功能（ＳＶ，ＣＯ，ＬＶＥＦ，ＳＴＩ）改善亦显著优于对照组；心肌酶（ＧＯＴ，ＣＫ，ＣＫ－ＭＢ，ＬＤＨ）峰值，住院期间心力衰竭及心律失常发生率亦均显著低于对照组。结论：ＤＡＸＸＫ是防治ＡＭＩ有较好疗效的纯中药制剂。     

酸性染料法测定盐酸地尔硫(艹卓)及其片剂含量的研究

目的 :根据盐酸地尔硫 艹卓 与溴甲酚绿形成有色离子对的性质 ,建立酸性染料法测定盐酸地尔硫 艹卓 及其片剂的方法。方法 :盐酸地尔硫 艹卓 与溴甲酚绿形成有色离子对络合物用氯仿萃取后比色。结果 :最大吸收波长λmas=(415±1)nm ,A -C回归方程为 :A =0 0 4 37C - 10 3 r=0 9996 (n =3) ,线性范围为 6 μg/ml～ 18μg/ml。结论 :该法灵敏准确 ,专属性强 ,便于普及     

地尔硫对冠心病的抗氧化作用

目的：观察地尔硫对冠心病病人的抗脂质过氧化及抗氧自由基作用。方法：冠心病病人３０例为治疗组（男性２１例，女性９例，年龄５８±ｓ６ａ），给予地尔硫３０ｍｇ，ｐｏ，ｔｉｄ，共４ｗｋ。健康人组３０例（男性１８例，女性１２例，年龄５８±９ａ）。结果：治疗组在给药前较健康人组的血清ｏｘＬＤＬ，ＬＰＯ，ＳＣＬ，ＬＣＬ值显著升高，Ｐ＜０．０１，ＧＳＨ－Ｐｘ显著降低，Ｐ＜０．０１，ＳＯＤ活力两者无明显差异，Ｐ＞０．０５。治疗组用药后与用药前相比ｏｘＬＤＬ，ＬＰＯ，ＳＣＬ，ＬＣＬ值显著下降，Ｐ＜０．０１或＜０．０５，ＧＳＨ－Ｐｘ显著升高，Ｐ＜０．０１，治疗组治疗后与健康人组相比，除ＬＣＬ外，其他指标皆无明显差异，Ｐ＞０．０５。结论：地尔硫是一良好的抗氧化剂。     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

硫氮(艹卓)酮对心肌钙反常损伤的影响

本实验建立心肌钙反常损伤模型,观察钙通道阻滞剂硫氮(艹卓)酮对心肌钙反常损伤的影响。发现硫氮(艹卓)酮能显著减轻心肌挛缩,提高冠脉流量和冠脉流出液中超氧化物歧化酶(SOD)活性,降低心肌细胞内的 CPK 释放及心室肌组织钙含量。实验结果表明,硫氮(艹卓)酮对心肌钙反常损伤有明显的保护作用。     

地尔硫静脉滴注治疗冠心病心绞痛

目的：观察地尔硫Ｚｈｕｏ注射液静脉滴注治疗冠心病心绞痛的疗效。方法：８６例心绞痛患者分为两组，其中治疗组４６例，用地尔硫Ｚｈｕｏ５０ｍｇ加入５％葡萄糖液２５０ｍｌ中静滴，１次／ｄ，连续１０ｄ；对照组４０例用丹参液１６ｍｌ加入５％葡萄糖液２５０ｍｌ中静滴，１次／ｄ，连续１０ｄ。结果：治疗组症状控制总有效率９８％，患者心电图改善率６１％，明显高于对照组的３７％和２８％，地尔硫Ｚｈｕｏ改善心功能效果明显     

Differential potentiation by calcium antagonists of neuromuscular blockade induced by pancuronium and succinylcholine in cats in vivo

Summary The effects of several calcium antagonists (verapamil, nicardipine and two diltiazem isomers, d-cis and l-cis diltiazem) alone and associated to non-depolarizing (pancuronium) and depolarizing (succinylcholine) neuromuscular blockers, were evaluated on sciatic nerve-tibialis anterior muscle preparations from cats in vivo. The calcium antagonists used (at 0.1 and 0.5mg/kg iv) did not modify the height of muscular twitches elicited indirectly. However, these agents potentiated in a dose-dependent way the neuromuscular blockade induced by iv pancuronium (2–40g/kg) and succinylcholine (6–200g/kg). The order of potency in increasing the effects of pancuronium was nicardipine d-cis diltiazem verapamil, whereas the order of potency in enhancing succinylcholine effects was d-cis diltiazem verapamil nicardipine. The effects of diltiazem were stereoselective, thus the potentiation induced by d-cis diltiazem was significantly greater in all cases than that induced by l-cis diltiazem, which suggests that calcium channel blockade plays a role in these interactions. However, other mechanisms such as calcium antagonists-induced nicotinic receptor desensitization may also be involved.     

曲美他嗪治疗稳定劳累型心绞痛患者的临床研究

目的：评价曲美他嗪与合心爽联合治疗稳定劳累型心绞痛的临床效果。方法：经服用合心爽不能有效控制的稳定劳累型心绞痛患40例,被随机分为联合曲美他嗪治疗组和单用合心爽治疗组,经治疗后评价两组心绞痛发作频度。结果;联合曲美他嗪治疗后患心绞痛的每周发作次数、动态心电图监测心肌缺血时间及硝酸甘油消耗量均有明显下降。结论：合心爽不能有效控制的稳定劳累型心绞痛患,联合应用曲美他嗪治疗能明显增加临床疗效,而不影响血液动力学。     

盐酸地尔硫（上）艹（下）卓控释胶囊在健康志愿者的人体药动学与生物等效性研究

 目的研究国产和进口盐酸地尔硫控释胶囊在健康人体内的代谢动力学过程，并评价这两种制剂的生物等效性。方法单剂量(180 mg)、多剂量(180 mg·d^-1×6 d)试验各选20例受试者，受试者随机分组、自身对照口服药物，采用反相HPLC测定血浆中地尔硫的浓度。结果单剂量时，参比制剂与受试制剂主要药动学参数c_max分别为(80.8±25.0)及(89.0±25.6) μg·L^-1；t_max分别为(5.75±2.02)及(6.00±2.55) h；t_1/2分别为(11.44±1.41)及(10.80±1.44) h；AUC_0～t分别为(1 635.6±355.7)及(1610.5±311.7) μg·h·L^-1；AUC^0～∞分别为(1681.1±356.9)及(1 648.8±312.1)μg·h·L^-1；受试制剂相对于参比制剂的生物利用度F为(100.0±17.1)%。多剂量时，参比制剂与受试制剂主要药动学参数c_max分别为(177.6±47.0)及(164.3±36.8) μg·L^-1；c_min分别为(44.3±16.3)及(40.3±14.7) μg·L^-1；t_max分别为(3.88±2.21)及(3.73±2.20) h；t_1/2分别为(10.27±3.05)及(10.73±2.72) h；AUC_SS分别为(2 328.9±637.3)及(2168.8±544.5) μg·h·L^-1；c_av分别为(97.0±26.6)及(90.4±22.7) μg·L^-1；DF分别为(142.9±32.3)及(139.5±31.3)%；受试制剂相对于参比制剂的生物利用度F为(94.6±12.3)%。结论统计分析结果显示，受试制剂与参比制剂生物等效。