Soft Drugs. XX. Design,Synthesis, and Evaluation of Ultra-Short Acting Beta-Blockers

A new type of ultra-short acting -blocker which might prove advantageous in treating acute arrhythmias was designed, synthesized and investigated. Based on the soft drug inactive metabolite approach, the inactive phenylacetic acid metabolite of both metoprolol and atenolol was reactivated by esterification with sulfur-containing aliphatic alcohols. Since the sulfur-containing moieties are labile to the ubiquitous esterases, the new compounds should be inactivated by a one step enzymatic cleavage back to the inactive phenylacetic acid derivative. Pharmacological and pharmacokinetic profiles of the new compounds were evaluated in rats and rabbits. Isoproterenol-induced tachycardia was inhibited with short-term infusion of each compound. This tachycardia blocking effect rapidly disappeared upon termination of infusion, while -blocking activity was 2–4-fold longer after comparable doses of the short-acting -blocker, esmolol. The rapid recovery from the -receptor blockade is believed due to fast hydrolysis of the soft drugs in the body. This is supported from in vitro results showing the t_l/2 of esmolol is about 10-fold longer than the new soft drugs in rat, rabbit, dog and human blood. Hydrolysis studies in phosphate buffered solutions indicated that the esters are labile to base-catalyzed hydrolysis. However, the relative t_1/2 values measured in biological media compared to phosphate buffered solution clearly support rapid enzymatic cleavage of the soft drugs. Interestingly, one of the soft -blockers, the sulfonyl ester derivative, showed a unique property of exhibiting good -receptor blocking activity without significant hypotensive action.     

恒力法测量制动对兔髌韧带截面面积的影响

目的：介绍一种测量软组织截面面积的装置和方法。方法：用测微仪对膝关节制动前后兔髌韧带截面面积进行反复测量。结果：测微仪的变异系数在０．９％以下,制动６周后髌韧带的截面面积明显增大。结论：兔髌韧带截面面积的这种变化与组织的胶原代谢水平相关     

Characteristics of bone mineral density and soft tissue composition of obese Japanese women: Application of dual-energy X-ray absorptiometry

We studied the characteristics of bone mineral density (BMD) and soft tissue composition in obese Japanese women using dual-energy X-ray absorptiometry. Eighty-nine women, aged 45–85 years, were divided into three groups according to their body mass index (BMI): a thin group (n = 38; BMI < 21), a standard weight group (n = 31; BMI, 21–25), and an obese group (n = 20; BMI ≥ 25). The mean BMD of the second to fourth lumbar vertebrae and BMD of the lumbar spine, thoracic spine, pelvis, legs, and ribs of the thin group were significantly lower than those of the standard weight group or the obese group (P < 0.05), whereas no significant difference in total body BMD was observed among the three groups. There was a significant difference in total and regional fat mass among the three groups (P < 0.05). Lean mass of legs and total lean mass showed a significant difference between the thin group and the obese group (P < 0.05). The results showed that obesity was associated with higher BMD of weight bearing-bones and ribs, high total and regional fat mass, and high lean mass of bilateral legs and total lean mass. We suggest that obesity may contribute to the prevention of bone loss of weight-bearing bones and ribs and muscular atrophy of the legs. Received: Sept. 30, 1998 / Accepted: Dec. 10, 1998     

复方云芝胶囊对丝裂霉素C诱发突变及老年自发突变的抑制作用

采用体外培养人淋巴细胞微核检测法,探讨复方云芝胶囊抗突变作用。结果表明,复方云芝胶囊（１０ｍｇ／Ｌ～５０ｍｇ／Ｌ）可显著抑制丝裂霉素Ｃ（ＭＭＣ）诱发的微核形成,并可拮抗老年人自发微核,增加细胞增殖活性。     

Neurological soft signs in schizophrenia: Assessment and correlates

A German version of the Neurological Evaluation Scale (NES) was administered to 143 schizophrenic patients, 45 of them being severly chronic and disabled. Seventy-eight alcohol-dependent inpatients and 57 healthy volunteers were tested as control groups. Neurological soft signs (NSS) were rated with convincing agreement. Schizophrenic patients are more impaired on all scales than healthy controls. The chronic, severly disabled schizophrenic patients are more impaired compared with the main group of schizophrenic patients and both control groups. A significant patients and alcohol-dependent patients was only found for the subscale Motor Coordination. Compared with healthy controls the alcohol-dependent patients show a higher NES total score. The NES total score was related to the relative width of the third ventricle. Total score and subscales were correlated consistently with the level of cognitive functioning as measured by the Raven Standard Progressive Matrices and various neuropsychological tests presumably sensitive to dysfunctions of the prefrontal cortex. The NSS were related to positive as well as to negative symptoms, the correlations with negative symptoms being confined to items of Cognitive Disorganization. This close association of psychomotor and cognitive dysfunctions may be seen as related to the frequently discussed dysfunctions of the prefrontal cortex or the neurointegrative deficit postulated by Meehl.     

Human pharmacokinetics and bioavailability of temazepam administered in soft gelatin capsules

Summary Plasma levels of temazepam were determined in healthy subjects after single oral administration of soft and hard gelatin capsules, and after 7 consecutive night-time doses in soft capsules. Absorption from soft gelatin capsules was significantly faster and produced earlier and higher peak plasma levels. The two pharmaceutical forms did not show any significant difference in relative availability. The apparent half-life of temazepam after night-time administration was significantly shorter than after morning administration, but no change in half-life was observed between the first and seventh night-time doses.     

用正交试验优选复方蒲香胶囊提取工艺

目的：研究复方蒲香胶囊的提取工艺。方法：采用正交试验法进行优选，测定复方蒲香胶囊中益母草有效成分含量。结果：煎煮时间、浸泡时间、煎煮次数、乙醇量等对益母草有效成分有显著影响。结论：最佳提取工艺为煎煮3次，平均每次1．5h，浸泡20rmin，1倍量乙醇。     

HPLC测定心可宁胶囊中原儿茶醛的含量

目的　采用高效液相色谱法测定心可宁胶囊中原儿茶醛的含量。方法　InertsilC1 8柱 (5 μm ,1 5 0mm× 4 .6mm) ;流动相为甲醇 - 0 .0 5mol·L-1 磷酸二氢钾缓冲液 (磷酸调pH 3.0 ) (2 0∶80 ) ;检测波长为 2 80nm。结果　原儿茶醛进样量在 0 .0 5 5 3～2 .2 1 30 μg范围内线性关系良好 (r=0 .9999) ;平均加样回收率为 99.7% (n =9) ;方法精密度RSD =0 .5 0 % (n =6 )。 结论　本方法操作简便、准确、重复性好 ,可作为该制剂中原儿茶醛的含量测定方法     

叶下珠复方胶囊合抗乙肝特异性转移因子治疗慢性乙型肝炎40例观察

目的 :观察叶下珠复方胶囊联合抗乙肝特异性转移因子治疗慢性乙型肝炎的疗效。方法 :治疗组用叶下珠复方胶囊每次 4粒 ,每天 3次 ;抗乙肝特异性转移因子 2 m g肌肉注射 ,每周 2次。对照组单用叶下珠复方胶囊每次 4粒 ,每天 3次。均治疗 6个月。结果 :治疗组总有效率 92 .5 % ,对照组总有效率 73.3% ,两组比较有显著性差异 (P<0 .0 5 )。但 HBe Ag、HBV- DNA阴转率治疗组分别为 5 5 .5 %、5 6 .2 % ,对照组分别为 4 4 .0 %、4 3.4 % ,两组比较无显著性差异 (P>0 .0 5 )。结论 :叶下珠复方胶囊联合抗乙肝特异性转移因子可提高疗效 ,起协同作用     

尼群地平缓释胶囊在家犬体内的药动学与相对生物利用度

目的研究尼群地平缓释胶囊在家犬体内的药代动力学与相对生物利用度。方法用高效液相色谱法测定了 6条健康家犬口服尼群地平缓释胶囊 (受试制剂 )和尼群地平普通片 (参比制剂 )后不同时间点血浆中尼群地平的浓度 ,绘制血药浓度 -时间曲线 ,计算药代动力学参数及相对生物利用度。结果受试犬口服含尼群地平 4 0mg的受试制剂和参比制剂后 ,血浆中尼群地平的tmax分别为 (6 1 7± 1 60 )和 (1 4 6± 0 5 1 )h;cmax分别为 (3 4 3 8± 1 2 2 6)和 (45 6 5± 1 0 7 4 )nmol L ;用梯形法计算 ,AUC0～t分别为 (1 93 0 1± 1 0 0 5 1 0 6)和 (1 790 8± 94 2 8)nmol·h L。以AUC计算 ,与参比制剂相比 ,受试制剂中尼群地平的相对生物利用度平均为 (1 1 0 5 9± 2 3 60 ) %。将AUC0～t经对数转换后进行方差分析 ,结果表明 ,受试制剂与参比制剂相比 ,除个体间外 ,周期间与制剂间无显著性差异 (P >0 0 5 ) ,受试制剂AUC0～t的 90 %置信区间为参比制剂的 88 5 4 %～ 1 3 1 93 %。结论尼群地平缓释胶囊与国外普通片相比 ,在犬体内具有更长的作用时间 ,且相对生物利用度相近