用滴丸法制备酒石酸锑钾丸的研究

一、绪言滴丸法系用一种熔点较低的脂肪基质或水溶性基质将主药溶解或混悬后,滴入一种不相混和的液体洽却剂中,由于熔融物表面张力的关系,形成小球形的丸剂.此方法于1933年丹麦哥本哈根的 Ferrossan 药物公司第一次应用于药剂上,设计了滴丸法的器械,并用氢化油作基质,用稀醇作冷却剂,制造维生素 AD 丸.另两篇专刊亦介绍了有关滴丸法机械的设计.以后 Sandell 氏 Ernerfeldt 氏及 Termansen 氏等相继发表了用     

Structure activity of C-terminal modified analogs of Ac-CCK-7

Previous work indicates that both the C-terminal phenylalanine amide and the tryptophan moieties of chole-cystokinin (CCK) are critical pharmacophores for interaction with either the A or B receptor subtypes. We have examined a series of analogs of Ac-CCK-7 [Ac-Tyr(SO₃H)-Met-Gly-Trp-Met-Asp-Phe³³-NH₂] (2) in which the phenyl ring of the C-terminal Phe-NH₂ has been modified. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors respectively and for anorectic activity after intraperitoneal administration to rats. Substitution of a number of cycloalkyi or bicyclic aryl moieties for the phenyl ring of phenylalanine³³ including cyclopentyl (20), cyclohexyl (21), cyclooctyl (23), 2-(5,6,7,8-tetrahydro)naphthyl (26), 2-naphthyl (27), and 1-naphthyl (29) led to analogs with 10–70 times the anorectic potency of 2. The anorectic activity of 21 was blocked by the specific CCK-A receptor antagonist MK-329. Other bulky aliphatic groups in place of the phenylalanine³³ aromatic ring such as isopropyl, 2-adamantyl and cyclohexylmethyl gave derivatives similar to 2 in potency. While most of the new compounds were comparable to CCK in binding assays, 23, 26, 27 and 29 were exceptionally potent with IC₅₀s 10^-11-10^-14 M in the pancreas. Compounds 23 and 29 were further evaluated for their ability to stimulate amylase secretion and found to have potencies similar to that of CCK. The dissociation between potency in the binding and amylase secretion assays suggests that they may interact with a high affinity binding site which is not coupled to amylase secretion. We conclude that CCK receptors possess a generous hydrophobic pocket capable of accommodating large alkyl groups in place of the side chain of phenylalanine³³ and that the pharmacological profile of CCK analogs can be tailored by appropriate exploitation of this finding.     

Comparisons of oral propafenone and quinidine as an initial treatment option in patients with symptomatic paroxysmal atrial fibrillation: a double-blind, randomized trial

Objective. The main aim of the study was to evaluate the safety and efficacy of propafenone versus quinidine as an initial choice in treatment of symptomatic paroxysmal atrial fibrillation. Design. The study consisted of a 3-month treatment with oral propafenone hydrochloride or quinidine sulphate in patients with paroxysmal symptomatic atrial fibrillation, according to a double-blind randomized system. Setting. The study was performed in the out-patient clinic of university hospital. Main outcome measures. The effects of the two drugs on attack frequency, ventricular rate and symptoms of symptomatic paroxysmal atrial fibrillation. Results. In the oral propafenone group (n=48), two patients (4%) discontinued the treatment because of dizziness. In the 46 patients who continued the treatment, the attack frequency decreased from 11±3 times per week at baseline to 1±1 times per week after treatment (P<0.01). Forty (87%) out of the 46 patients had effective response to oral propafenone (more than 75% reduction of symptomatic arrhythmic attacks) on a mean dose of 615±10 mg day^-1; the decrease in attack frequency was from 10±3 to 1±1 times per week. Twenty-three (50%) patients were free from recurrence of symptomatic paroxysmal atrial fibrillation. Comparisons of symptom scores for patients (n=23) with attacks of paroxysmal atrial fibrillation after oral propafenone treatment showed that there was a significantly lower symptom score of palpitation, asthenia, effort dyspnea, dizziness, rest dyspnea and chest oppression in attacks of paroxysmal atrial fibrillation after propafenone treatment (11.05±3.78 versus 7.60±3.46, P<0.01). From the oral quinidine group (n=48), two patients (4%) discontinued treatment because of gastrointestinal discomfort. In the 46 patients who continued the treatment, the attack frequency decreased from 11±4 times per week at baseline to 3±2 times per week after treatment (P<0.01). Twenty-one (46%) out of the 46 patients had effective response to oral quinidine on a mean dose of 1067±462 mg day^-1, with a decrease in attack frequency from 12±3 to 1±1 times per week. Only 10 (22%) patients were free from recurrence of paroxysmal atrial fibrillation. Comparisons of symptom scores for patients (n=36) with attacks of paroxysmal atrial fibrillation after quinidine treatment showed that there was no significant decrease of symptom score in attacks of atrial fibrillation (10.65±3.92 versus 10.20±3.80, P=0.57). Furthermore, the percentage decrease of ventricular rate during atrial fibrillation was significantly greater in patients with propafenone (-25±4% versus -8±3%, P<0.01). Conclusions. Oral propafenone appeared to be more effective than quinidine in suppressing attacks and alleviating symptoms of paroxysmal atrial fibrillation.     

Dimension and Related Anatomical Distance of Koch's Triangle in Patients with Atrioventricular Nodal Reentrant Tachycardia

Koch's Triangle in AVNRT. Introduction: The dimension of Koch's triangle in patients with AV nodal reentrant tachycardia has not been well described. Understanding the dimension and anatomical distance related to Koch's triangle might be useful in avoiding accidental AV block during ablation of the slow pathway. The purposes of this study were to define the dimension of Koch's triangle and its related anatomical distance and correlate these parameters with the successful ablation sites in patients with AV nodal reentrant tachycardia. Methods and Results: We studied 218 patients with AV nodal reentrant tachycardia. The distance between the presumed proximal His-bundle area and the base of the coronary sinus orifice (D_His-Os) measured in the right anterior oblique view was used to define the dimension of Koch's triangle. The distance of the proximal His-bundle recording site from the successful ablation site (D_His-Ab) and the distance as a fraction of the entire length of Koch's triangle (D_His-Ab/D_His-Os) were determined. The mean D_His-Os, and D_His-Ab were 25.9 ± 7.9 and 13.4 ± 3.8 mm, respectively. D_His-os negatively correlated with patient age (r = -0.41, P < 0.0001) and body mass index (r = -0.18, P = 0.004). Among the patients with successful ablation sites in the medial area, D_His-Os was longer (27.2 ± 6.6 vs 24.6 ± 8.4 mm, P < 0.005), D_His–Ab was similar (12.9 ± 3.1 vs 13.9 ± 4.0, P > 0.05) and D_His-Ab/D_His-Os was smaller (0.48 ± 0.04 vs 0.74 ± 0.11, P < 0.05). Furthermore, the patients with successful ablation sites in the medial location needed more radiofrequency pulse numbers than those in the posterior location (6 ± 4 vs 4 ± 3, P < 0.05). Conclusion: The site of successful slow pathway ablation was consistently about 13 mm from the site recording the proximal His-bundle deflection in patients with AV nodal reentrant tachycardia despite marked variability in the dimensions of Koch's triangle: therefore, patients with large triangles required ablation in the medial region rather than the posterior region. Care should be taken when delivering radiofrequency energy to the posteroseptal area in patients with shorter D_His-Os to avoid injury to AV node.