硝酸异山梨醇透皮给药系统的研制

硝酸异山梨醇透皮给药系统(ISDN—TDS)由背衬层、药库、乙烯—醋酸乙烯共聚物(EVA)控释膜、压敏胶及防粘层组成。采用Keshary—Chien体外释药装置,研究了药库组分、基质溶剂、控释膜、压敏胶粘度及透皮给药促进剂氮酮等对药物释放的影响。以释异丁烯、矿物油、EVA控释膜为主要材料制成的ISDN—TDS体外能持续释药72h,0～48h药物按零级动力学经皮透过。平均释药速率为13.76μg·h^-1/cm²,而国外类似产品Frandol tape-s按Higuchi模型释药仅24h。     

Bronchodilator effect of sublingual isosorbide dinitrate in asthma

Summary The bronchodilating effect of 5 mg sublingual isosorbide dinitrate (ISDN) was studied in 10 patients with bronchial asthma, using the doubleblind randomised cross-over method with matched placebo. In a further 20 asthmatics the effect of sublingual ISDN was compared with that of metaproterenol given by a metered dose inhaler to a total dose of 2.25 mg, again using the cross-over method. The forced oscillation method was used to measure respiratory resistance (Rrs) and spirometry was used to measure vital capacity (VC) and forced expiratory volume in one second (FEV₁). 5 minutes after administration of ISDN Rrs had decreased (p<0.05) and VC (p<0.01) and FEV₁ (p<0.01) were significantly increased. The changes were still present after 15, 30 and 60 min. The placebo had no significant effect. ISDN increased FEV₁ less than metaproterenol, and the difference between them was statistically significant (p<0.05). However, there was no significant difference between ISDN and metaproterenol in the improvement in Rrs and VC. Of the total of 30 patients, 11 experienced headache and 4 had transient hypotension after ISDN administration. These side effects subsided spontaneously. It was concluded that sublingual ISDN had a bronchodilating effect in stable asthmatics.     

Comparative vasodilator effects of nitroglycerin,pentaerythritol trinitrate and biometabolites,and other organic nitrates

Previous studies in man have shown pentaerythritol (PE) trinitrate, given either sublingually or orally, produces a prolonged hypotensive effect. The coronary vasodilator and systemic vasoddepressor activities of PE trinitrate and its metabolites, PE dinitrate, PE mononitrate and PE, were evaluated in dogs to determine whether the metabolites were active and contributory. Coronary vasodilator activity was estimated with a flow transducer placed on the left anterior descending artery, and reduction of arterial pressure was determined directly via the femoral artery. Quantitative comparisons were made from dose—response curves established for nitroglycerin (NG), PE nitrates, and other common organic nitrates after intrajugular administration. Increase of coronary blood flow and reduction of arterial pressure were proportionally related, and the proportionality was the same for all drugs. Relative to NG, the potency of PE trinitrate was about 20%, erythrityl tetranitrate 12%, and isosorbide dinitrate 3.5%. The ratios of vasodilator activity of PE trinitrate and its metabolites were: PE trinitrate 100; PE dinitrate 1.5; PE mononitrate 0.5; and PE 0. Tachyphylaxis was observed after close-order injections of NG or PE trinitrate. In addition, there was cross tolerance between NG and PE trinitrate and also between PE trinitrate and its less active metabolites.     

益气温阳利水汤联合西药治疗充血性心力衰竭随机平行对照研究

[目的]观察益气温阳利水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例门诊患者按就诊顺序编号简单随机分为两组。对照组41例地高辛0.125~0.25mg/次,1次/d;硝酸异山梨酯10mg/次,3次/d;双氢克尿噻12.5~25mg/次,2次/d;培哚普利4mg/次,1次/d。治疗组39例益气温阳利水汤(熟附子先煎、生黄芪、葛根各30g,茯苓15g,葶苈子包煎30g,丹参15g),水煎150m L,1剂/d,早晚温服;西药治疗同对照组。连续治疗7d为1疗程。观测临床症状、心功能、不良反应。连续治疗2疗程,判定疗效。[结果]治疗组显效35例,有效5例,无效1例,总有效率97.56%。对照组显效28例,有效4例,无效7例,总有效率82.05%。治疗组疗效优于对照组(P0.01)。心率和血压两组均有改善(P0.05),治疗组优于对照组(P0.05);肾上腺素和去甲肾上腺素两组均有改善(P0.05),治疗组优于对照组(P0.05)。[结论]益气温阳利水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。     

舌下含服硝酸异山梨酯对16层螺旋CT冠状动脉成像的影响

目的探讨舌下含服硝酸异山梨酯对16层螺旋CT冠状动脉成像质量和管腔直径的影响。方法50例临床怀疑冠心病者随机分为A(不含服硝酸异山梨酯,25例)、B(含服硝酸异山梨酯5mg,25例)两组,进行16层螺旋CT冠状动脉成像,分别观测右冠状动脉、左主干、左前降支、左旋支四个主要节段的管腔直径和14个节段的显示情况以及患者副反应。结果B组冠状动脉4个主要血管节段直径明显大于A组;两组右冠状动脉(第1、2、3段)、左主干(第5段)、左前降支(第6、7段)、左旋支(第11段)可评价例数相同;左室后支(第14段)、左前降支(第8段)、第1、2对角支(第9、10段)、钝缘支(第12段)、左旋支(第13段)显示差异有显著性,而两组副反应差异无显著性。结论含服硝酸异山梨酯可扩张冠状动脉,提高MSCT冠状动脉细小分支的显示率和成像质量,而不增加副反应率。     

通心络胶囊治疗冠心病耐药性的临床研究

目的探讨通心络胶囊治疗冠心病的耐药性.方法60例冠心病病人随机分为两组,治疗组30例,口服通心络胶囊,每次3粒,每日3次;对照组30例,口服消心痛,每次10mg,每日3次,疗程8周.观察2、4、6、8周时的心绞痛、心电图(ECG)变化.结果疗程2周时治疗组和对照组心绞痛、ECG有效率无显著差异(P＞0.05);疗程8周后两组心绞痛、ECG有效率有统计学差异(P＜0.01),治疗组优于对照组;治疗组6周时心绞痛、ECG有效率无明显变化,与2周时比较P＞0.05;对照组6周与2周相比心绞痛有效率降低,P＜0.05.结论长期服用通心络胶囊治疗冠心病疗效显著稳定,无耐药性.     

Role of both actin–myosin cross bridges and NO-cGMP pathway modulators in the contraction and relaxation of human placental stem villi

Introduction

Human placental stem villi (PSV) present contractile properties. We studied the role of actin–myosin cross bridges (CBs) and the effects of NO-cGMP pathway modulators in the PSV contraction and relaxation.

Methods

In vitro contractile properties were investigated in 71 PSV from term human placentas studied according to their long axis. Contraction was induced by both KCl and electrical tetanic stimulation. Relaxation was induced by inhibiting the CB cycle with either 2,3-butanedione monoxime (BDM) or blebbistatin (BLE) and by activating the NO-cGMP pathway with isosorbide dinitrate (ISDN), sildenafil (SIL) or ISDN + SIL.

Results

PSV tension slowly increased by 140% of the basal tone after KCl exposure and by 85% after tetanus. The addition of BDM, BLE, ISDN, SIL and ISDN + SIL induced a relaxation of PSV, the overall time course of relaxation (in s) was respectively (means ± SD) 3412 ± 1904, 14,250 ± 3095*, 3813 ± 1383, 2883 ± 1188 and 2440 ± 477; significantly longer in BLE compared with BDM, ISDN, SIL and ISDN + SIL:*p < 0.001). the overall time course of relaxation (in s) was respectively (means ± SD) 3412 ± 1904, 14,250 ± 3095*, 3813 ± 1383, 2883 ± 1188 and 2440 ± 477; significantly longer in BLE compared with BDM, ISDN, SIL and ISDN + SIL:*p < 0.001). These relaxation kinetics were particularly slow. Other relaxation parametres, i.e., maximum lengthening, -peak dT/dt, and resting tension, did not differ between these 5 subgroups.

Discussion and conclusion

Isolated human PSV were able to contract after both KCl exposure and tetanus. This increase in contractility was reversed by inhibiting the CB cycle with BDM or BLE and by stimulating the NO-cGMP pathway with ISDN or SIL. The association ISDN + SIL did not potentiate the relaxing processes     

活血通脉汤治疗冠心病心绞痛临床研究

目的：探讨活血通脉汤治疗冠心病心绞痛的临床疗效。方法：160例冠心病心绞痛患者按随机数字表法分为对照组和观察组,每组各80例。对照组给予单纯西医治疗,观察组采用活血通脉汤治疗,观察两组临床疗效。结果：对照组有效率为83.75%,观察组有效率为92.50%,两组比较差异具有统计学意义（ P〈0.05）。结论：活血通脉汤治疗冠心病心绞痛疗效可靠,能显著改善临床症状,改善心电图状况,减少心绞痛发作次数。     

麝香保心丸与硝酸异山梨酯联合治疗无症状性心肌缺血的效果研究

目的探讨无症状性心肌缺血患者使用麝香保心丸与硝酸异山梨酯联合治疗后的临床效果。方法选择来我院就诊的无症状性心肌缺血患者72例作为本次研究对象,随机分为两组。观察组（n=36）采用麝香保心丸联合硝酸异山梨酯进行治疗,对照组（n=36）采用硝酸异山梨酯进行治疗,对两组患者的心电图心肌缺血改善情况及血脂、血液动力学观察指标进行对比分析。结果观察组患者与对照组比较,心电图缺血改善情况中有效率明显较高,两组差异具有显著性（P〈0．05）。治疗后观察组患者的全血黏度高切值、全血黏度低切值、血浆比黏度、TG、TC均显著降低,与对照组治疗后比较改善情况明显较好（P〈0．05）。所有患者治疗后均未发现不良情况。结论无症状性心肌缺血患者在采用麝香保心丸联合硝酸异山梨酯治疗后能够收到较好的临床效果。可以在临床推广应用。