羟甲基烟酰胺分散片的研制

目的：研制羟甲基烟酰胺分散片。方法：以崩解时间为指标。比较几种崩解剂的作用，以正交试验设计确立最佳处方，并与普通片进行体外溶出度比较。结果：崩解剂以低取代羟丙纤维素(L-HPC)效果最优，最佳处方崩解时间为78．9S，溶出速度远大于普通片。结论：所研制的羟甲基烟酰胺分散片溶出迅速。     

心脏营养素-1治疗失神经骨骼肌萎缩过程中对正常肌肉组织的影响

目的 探讨应用心脏营养素-1(cardiotrophin-1,CT-1)治疗失神经骨骼肌萎缩的有效剂量和安全剂量,观察不同剂量的CT-1对正常骨骼肌、心肌和血管平滑肌的副作用.方法 取Swiss小鼠80只,随机分成8组,每组分别于胫神经切断术后连续腹腔注射重组小鼠CT-1(rmCT-1)40、60、80、100、120、140、160μg·kg-1·d-1,剩余1组腹腔注射等体积CT-1溶媒,28d后称量失神经侧腓肠肌、正常侧腓肠肌和心脏的湿重;测量胸主动脉平滑肌厚度;检测正常腓肠肌中α-actin和MHC Ⅱa以及心肌中β-MHC的表达、胸主动脉血管平滑肌细胞中α-actin的含量.结果 采用腹腔注射给药,当CT-1用量达到60μg·kg-1·d-1时,开始对失神经骨骼肌产生营养作用,并呈剂量依赖性增强,当给药剂量超过100 μg·kg-1·d-1后,出现对正常骨骼肌、心肌和血管平滑肌的影响.给药剂量达到120μg·kg-1·d-1时,开始促进心肌β-MHCmRNA的表达,增加正常心脏的湿重.当给药剂量达到140μg·kg-1·d-1时,开始促进正常骨骼肌α-actin和MHC Ⅱ amRNA的表达,以及骨骼肌湿重的增加,同时提高了主动脉血管平滑肌α-actin的含量,增加了血管平滑肌的厚度.结论 腹腔注射CT-1防治失神经骨骼肌萎缩的有效剂量为60 μg·kg-1·d-1,最高安全剂量为100 μg·kg-1·d-1.当给药剂量达到120 μg·kg-1·d-1时,开始出现心肌肥厚,当给药剂量达到140 μg·kg-1·d-1时,可导致正常骨骼肌的肥大和血管平滑肌的增厚.     

根据桂枝汤的效应消除半衰期和表观消除半衰期制订给药方案的探讨

为探讨药效法估测的效应消除半衰期和效量法估测的表观半衰期对合理制订给药方案的意义和作用,以桂枝汤解热和抗炎的药物动力学实验中所得的相应参数值设计了给药方案,观察了它们在提高药效上的作用。结果表明在给药总剂量相等、首次给药同时开始的情况下,以半衰期设计的给药方案组的药效均明显高于习惯的一次给药组;而以效应消除半衰期设计给药方案组药效增强率又高于以表观半衰期设计的方案组。提示效应消除半衰期比表观半衰期似更有实践意义。     

Moclobemide versus fluoxetine for a major depressive episode

The efficacy and tolerability of moclobemide (300–600 mg daily) and fluoxetine (20–40 mg daily) were compared in a 6-week, double-blind study of 65 inpatients and 34 outpatients suffering from major depressive episodes (DSM III-R). No statistically significant differences between the two treatment groups were noted regarding efficacy (HDRS, CGI) or safety (adverse events, laboratory examination, vital signs). Moclobemide (300–600 mg daily) and fluoxetine (20–40 mg daily) would thus appear to be comparable both in antidepressant efficacy and tolerability. Doubling the low dosage in non-responders after 3 weeks resulted in a statistically significant improvement of CGI in the moclobemide group by comparison with the fluoxetine group at study end, suggesting that 600 mg moclobemide/day can still improve the patient's condition, while 40 mg fluoxetine/day does not. Sexual dysfunction was reported in two patients taking fluoxetine.     

提高尿激酶原治疗急性心肌梗死疗效研究

尿激酶原是新一代特异性溶栓药。为进一步提高该药的安全性和有效性,本文从使用剂量、给药方案、与其他溶栓药伍用,及给药途径等方面提出了意见,供临床医生使用中参考。     

German experimental hepatitis B vaccine — Influence of variation of dosage schedule,sex and age differences on immunogenicity in health care workers

Summary Of the medical staff of our hospital 217 members at high risk for hepatitis B were immunized with an experimental hepatitis B vaccine and anti-HBs titers used to study the influence of two dosage schedules, age, and sex on immunogenicity. Participants were 34 years of age (mean; range, 20–61); they were divided into two groups and vaccinated three times. Group A received 42 µg HBsAg for each vaccination. Group B received 84 µg for the first and 21 µg for the second and third vaccinations. The seroconversion rate was 32.7% after the first, 78.8% after the second, and 95.7% after the third vaccination. The participants who failed to produce anti-HBs titer (3 IU/l;n=9) or whose anti-HBs titers were below 50 IU/l (n=31) were vaccinated a fourth time. Only mild side effects of injections were observed in a third of all participants, usually in the form of a sore arm.Between groups A and B there were no significant differences as far as the seroconversion rate and anti-HBs titer were concerned. Nonresponders plus low-responders accounted for 19%. Female participants produced a markedly higher anti-HBs titer than males, and the female/male ratio among non- and low-responders was 1:2; among nonresponders, 1:2.5. There was a negative correlation of the anti-HBs titer with the age of the participants. These results not only have practical consequences for revaccination policy, but also offer the opportunity to further study the genetic regulation of the immune response to a complex peptide antigen in man.Abbreviations anti-HBc antibody to hepatitis B core antigen - anti-HBe antibody to hepatitis B e antigen - anti-HBs antibody to hepatitis B surface antigen - HBsAg hepatitis B surface antigen - IU/l international units per liter - MSD Merck, Sharp, and Dohme     

The detection of chemical impurities by high pressure liquid chromatography and the genetic activity of medical grades of pyrvinium pamoate inSaccharomyces cerevisiae andSalmonella typhimurium

The genetic activity of several medical grades of the anthelmintic drug pyrvinium pamoate, which is a dipyrvinium salt, was studied in a diploid mitotic recombination and gene conversion assay (strain D5 ofSaccharomyces cerevisiae), and in several haploid yeast reversion assays (strains XV185-14C, XY718-1A, and 7854-1A). All of the samples were recombinogenic in strain D5 and mutagenic in the haploid strains, however, the degree of genetic activity varied considerably among the medical grades of pyrvinium pamoate that were tested. Similarly, these samples varied in degree of mutagenicity when they were tested in strains TA97, TA98, TA100, and TA102 ofSalmonella typhimurium, but some of the medical grades of pyrvinium pamoate were mutagenic both in the presence and in the absence of the metabolic transformation system, whereas other medical grades of the drug required such activation to be mutagenic. In addition, the medical grades and dosage forms of several brands of pyrvinium pamoate were examined for purity by fluorescence high pressure liquid chromatography (HPLC) using a methanol:water (9010) solvent system. The HPLC data indicate that monopyrvinium salts are the major contaminants in these pharmaceuticals. In general, there is a correlation between the degree of genetic activity and toxicity, and the number and relative quantity of impurities found in each sample.     

患儿术后硬膜外注入曲马朵镇痛使用剂量的临床研究

目的 研究患儿术后用曲马朵镇痛的使用剂量。方法 择期手术后患儿32例,随机分为A、B两组（每组16例）,硬膜外注入曲马朵观察镇痛效果,其中A组注入曲马朵1mg/kg,B组注入曲马朵1.5mg/kg,其它用药相同。结果 A、B两组用药后的R、VT、SpO2无显著差异,A、B两组在用药后的镇痛效果的差异无统计学意义,但B组的副作用明显强于A组。结论 小儿硬膜外一次性注入曲马朵进行术后镇痛安全、可靠,为减少副作用,曲马朵用量以1mg/kg为佳。     

始创药物及剂型研究

1 始创药物研究的意义和方向 药物是特殊产品.一是因为药品生产具有国际性和垄断性.创造出一种不可代替的新药,便可迅速占领全球市场.二是因为它是关系人民健康和生产力、战斗力强弱的极其重要的物资.一个国家的基本药物的供给、生产如果大部分掌握在外国人手里,则在和平时期,受到国际资本的盘剥,在战争或大灾害时期更要受制于人.因此,世界强国无不从战略的高度,从基础研究开始,独立自主地开发新药.十几年来,我国的新药研究、生产和供应面临严重的挑战.知识产权问题冲击了以仿制为主的原有制药工业,而过去创新研究又很薄弱,所以不得不引入外国技术和产品.由于它们与外国资本是两位一体的,所以经过几年的转轨,虽然解决了相当一部分药品的供应问题,但是由于我们自己没有独立创造的新型药物和制剂,所以我国的制药工业面临极大困境.如果长期处于让外国人创新,我们引进的状态,不仅在经济上损失极大,而且让外国技术和产品占领基本用药市场,遇有非常情况,便会被外国人卡住脖子.因此,有识之士呼吁支持始创药物研究,开发有始创性的药物,也去占领国际市场.应看到我们的新药研究仍然是跟踪国际上已经有的药物或已经有的基本结构.在目前拼实力、拼速度的时候,我们靠这种方式很难赶在人家的前面.始创药物研究必需有新思路和新方法.     

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone as a redox titrant

An oxidimetric titrant, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in anhydrous acetic acid is used for the semimicro-determination of hydrazine hydrate, phenylhydrazine hydrochloride, isoniazid and iproniazid phosphate in pure forms as well as in some pharmaceutical preparations containing isoniazid and iproniazid phosphate. The end point was detected potentiometrically using a platinum-calomel combination electrode. The results obtained are compared statistically with those obtained by the official methods and they are in good agreement.