蕲蛇酶注射液

【通用名称】　AcutobinInjection,蕲蛇酶注射液蕲蛇酶注射液是福建医科大学王晴川、刘广芬教授经过十几年精心研制成功的,由福建医科大学和福建汇天生物药业有限公司(原福建省三明制药厂)联合开发生产。现已被国家药品监督局正式批准为西药类国家二类新药,荣获国家技术创新优秀项目,被列为国家重点工业性实验项目。蕲蛇酶注射液是从尖吻蝮(Agkistrodonacute)蛇毒中采用高科技生物化学方法,分离提纯、精制而成的凝血酶样酶(Thrombinlikeenzynts),其分子量为27000±3000Da。蕲蛇酶注射液为无色澄明溶液,它作用于血浆纤维蛋白原,可使血浆纤…     

重组可溶性TRAIL冻干保护剂的初步筛选

目的 筛选出适合肿瘤坏死因子相关凋亡诱导配体（TRAIL）冻干制剂的保护剂。方法在TRAIL蛋白中加入不同浓度配方的甘露醇、清蛋白和乳糖，经过冷冻干燥，观察冻干制剂的色泽、外观、溶解度和澄明度，并且测定冻干制品的水分和生物学活性，筛选出最佳保护剂。结果初步筛选出2％甘露醇＋3％乳糖作为TRAIL蛋白的保护剂。结论 TRAIL蛋白药物加入该保护剂后，外观、溶解度、澄明度及生物活性都比较好。在不同温度，对TRAIL蛋白生物活性有很好的稳定作用。     

三种蝮蛇抗栓酶的毒性及性质的实验研究

目的:对三种蝮蛇抗栓梅的毒性及其性质进行实验研究。方法:小白鼠尾静脉注射急性毒性实验法和家兔亚急性毒性实验法。结果:三种蝮蛇抗栓酶的毒性强度用LD_50表示,分别是,蛇岛蝮蛇抗栓酶为1.68±0.35u/kg,东北陆生白眉蝮蛇抗栓酶为5.223±0.61u/kg,浙江蝮蛇抗栓酶为1.94±0.15u/kg。对家兔亚急性毒性实验表明,对血细胞、肝及肾功能、脏器等无明显影响。     

蕲蛇酶注射液治疗急性脑梗塞31例

目的：对蕲蛇酶注射液治疗急性脑梗塞３１例进行临床安全性及有效性评价。方法：采用蕲蛇酶注０．７５静滴,ｑｄ,７ｄ为一疗程,停药５ｄ后开始第２疗程。结果：经２个疗程治疗,总有效率为９０．３％。结论：蕲蛇酶注射液是治疗急性脑梗塞安全有效的药物。     

蕲蛇酶注射液治疗血脂异常的临床研究

目的 蕲蛇酶注射液治疗血脂代谢异常的临床疗效。方法 皮试阴性者，用蕲蛇酶注射液0．75—1．5u溶于250ml或500m1生理盐水中静滴，每日1次，连用7—14d为一疗程。结果 临床观察32例，显效6例，有效24例，无效3例，总有效率93．75％(P＜0．05)。结论 蕲蛇酶注射液静滴对血脂代谢异常有明显治疗作用。     

蕲蛇酶与降纤酶的生物活性比较

目的比较蕲蛇酶和降纤酶在试管内的酶活力及在兔体血液凝固系统的生物活性。方法分别体外测定蕲蛇酶和降纤酶的相对分子质量(Mr)、蛋白质含量、精氨酸酯酶活力和凝血酶活力等。分别给家兔静脉注射蕲蛇酶0.75U/kg和降纤酶5U/kg,连续3d,比较给药前后纤维蛋白原含量、凝血酶时间、凝血酶原时间、部分凝血酶活酶时间、血小板数目、血小板聚集率、血栓长度及血栓重量的变化。结果蕲蛇酶Mr比较小(27000),且由2个Mr为15500的亚基构成,降纤酶Mr较大(40900),为单链蛋白质。0.75U蕲蛇酶和0.21U凝血酶相当;5U降纤酶约相当于1.4U凝血酶.蕲蛇酶的精氨酸酯酶活力为(973±14)μmolTAME/(mg.min),降纤酶的精氨酸酯酶活力为(1140±18)μmolTAME/(mg.min)。家兔实验,两者均能减少血栓形成及降低纤维蛋白原含量,但蕲蛇酶的药效比降纤酶强,其余指标无明显差异。结论蕲蛇酶与降纤酶不同,蕲蛇酶在生物体内(家兔)表现的药效比降纤酶强。     

蕲蛇酶治疗48例急性脑梗塞的近期疗效观察

目的 观察蕲蛇酶对急性脑梗塞的近期治疗效果。方法 将８０例急性脑梗塞随枘发成两组，治疗组４８例，给予蕲蛇酶１５０μｇ静滴，每日１次，治疗１０天，对照组３２例，给予脉要２０ｍｌ加入低分子右旋糖酐２５０ｍｌ静滴，每日１次，治疗１４天。结果 治疗组显效率７２．９％，对照组３７％（Ｘ＾２＝９．４９，Ｐ〈０．０１）。结论 蕲蛇酶对急性脑便垢治疗能显著改善临床症状，降低致线率。     

精纯抗栓酶治疗急性脑梗塞的疗效观察

评价精纯抗栓酶对急性脑梗塞的临床疗效。方法：采用随机、开放、对照的方法将急性脑梗塞患者126例分为治疗组对例与对照组56例，治疗组应用精纯抗栓酶首次20U，以后10U，加入生理盐水250ml静脉滴注，隔日给药，4次为一疗程；对照组应用蝮蛇抗栓酶常规治疗。结果：治疗15天后治疗组总有效率为84．29％，对照组为64．29％（P＜0．01），治疗后纤维蛋白原降低治疗组比对照组更明显（P＜0．01）。结论：精纯抗栓酶治疗急性脑梗塞疗效确切，副反应少。     

巴曲抗栓酶对脑梗死病人的血液流变学及纤溶的作用

目的：观察巴曲抗栓酶对脑梗死病人血液流变学及纤溶的作用。方法：６０例脑梗死病人分为３组，巴曲抗栓酶组２０例，首次给１０ＢＵ，继而隔日５ＢＵ，加入０．９％氯化钠注射液２５０ｍＬ中静脉滴注（静滴），共３次（总量２０ＢＵ）；蝮蛇抗栓酶组１８例，给精制蝮蛇抗栓酶０．５Ｕ加入０．９％氯化钠注射液２５０ｍＬ中静滴，ｑｄ×１４ｄ；右旋糖酐组２２例，给右旋糖酐４０，５００ｍＬ加丹参注射液１６ｍＬ静滴，ｑｄ×１４ｄ。结果：３组均有不同程度改善血液流变学作用；在纤溶指标方面，巴曲抗栓酶组与蝮蛇抗栓酶组均显著降低凝血因子Ｉ及增加Ｄ－二聚体（Ｄ－ｄｉｍｅｒ）作用（Ｐ＜０．０５）；巴曲抗栓酶组尚有降低α２纤溶抑制物作用（Ｐ＜０．０５）。而另２组则无；巴曲抗栓酶总有效率达８５％。３组疗效相信相仿。结论：巴曲抗栓酶降血粘度及溶栓效果好，治疗脑梗死疗效高。     

蝮蛇抗栓酶在皮肤科的应用

蝮蛇抗栓酶在皮肤科的应用古维新姚育法（第一军医大学珠江医院广州５１０２８２）我们就近年来蝮蛇抗栓酶（抗栓酶）在皮肤科的应用作一综述。１银屑病据报道［１］，用抗栓酶０．５～０．７５ｇ加入５％或１０％葡萄糖液２５０～５００ｍｌ中静脉滴注，１次·ｄ－１，１...     

对临床试验中显著性检验、区间检验及置信区间检验之间关系一致性的认识

显著性检验是最基本的统计假设检验,它的基本思想是小概率原理;区间检验是传统显著性检验的延伸,它用来检验两个总体的差异是否在某范围之内;置信区间检验是先找到药物疗效差值的置信区间,通过置信区间下限或(和)上限与界值的关系来判断两种药物非劣效、等效、优效的关系。通过公式推导发现,区间检验与显著性检验的主要区别是前者的假设中包含了有临床意义的界值△,而区间检验和置信区间检验是一致的,可以用置信区间检验实现区间检验的目的。     

谈谈两总体比较的非参数检验方法

针对不同的数据类型,探讨选用不同的非参数检验方法,并通过实例说明这些非参数检验方法的应用。     

A Comparison of Two-Sample Tests of Significance When Used With Variable Treatment Effects

This article compares the performance of many two-sample tests of significance that might be used to test the equality of means when the effect of the treatment is variable. Of the 19 tests that were compared, the normal scores test is recommended for general use in testing the null hypothesis of no treatment effect against the alternative that the distributions are stochastically ordered when the ratio of the larger standard deviation to the smaller standard deviation does not exceed 1.3. The Baumgartner-Weiß-Schindler tests and an adaptive test also have higher power than the pooled t-test, the unequal variance t-test, and the rank-sum test for many distributions. In the simulation studies, data in the first sample are generated from nine distributions, including long-tailed and skewed distributions. Data in the second sample are generated by adding a random treatment effect to a random variable that was generated from the same distribution that was used in the first sample. Because we restricted our power studies to treatment effects that are positive or zero, the population distributions will be stochastically ordered. The results of these studies demonstrate that the normal scores test is often more powerful than the t-tests and the rank-sum test. If the ratio of the standard deviations does exceed 1.3, then one of the t-tests is recommended.     

Testing equality of proportions for correlated binary data in ophthalmologic studies

In ophthalmologic studies, bilateral correlated data often arise when information involving paired organs (e.g., eyes) are measured from each subject. Adjusted chi-square approach for testing the equality of proportions has been proposed in the literature. In this article, we investigate and derive three alter- native testing procedures for the problem. Our simulation results show the score testing procedure usually produces satisfactory type I error control with higher power, and therefore is recommended. Examples from ophthalmologic studies are used to illustrate our proposed methods.     

中国药品上市后抽验模式现状及问题

目的在综合分析中国药品上市后抽验模式现状及问题的基础上,提出药品上市后抽验的建议。方法通过文献研究的方法,发现中国药品上市后抽验模式中存在的问题,并提出相关建议。结果与结论在药品抽验中引入以风险为基础的抽验模式,将药品上市后抽验结果与药品监管相衔接。     

Mutagenicity testing of quinine with submammalian and mammalian systems

Quinine hydrochloride was assayed for genotoxic activity by using 4 different test systems with distinct genetic endpoints. No indications for point mutations were observed in the Ames system. In 3 cytogenetic tests performed on small rodents, Chinese hamsters showed no genotoxic activity, while inbred strains of mice revealed a dose dependent increase of SCEs, enhanced incidence of micronuclei and elevated chromatid breaks.     

刹毒草口服液的药理作用研究

目的:研究刹毒草口服液对小鼠的药理作用。方法:用小鼠分别进行爬杆实验、炭粒廓清实验、耳肿胀实验和墨汁推进实验,观察刹毒草口服液对小鼠的抗疲劳作用、非特异性免疫功能的影响、抗炎作用和抗腹泻作用。结果:刹毒草口服液能显著延长小鼠爬杆时间,有较好的抗疲劳作用;高剂量刹毒草口服液能显著提高小鼠对惰性炭粒的吞噬指数及吞噬活性,可提高小鼠免疫功能;刹毒草口服液3个剂量组均对二甲苯致小鼠耳炎症有较好的抑制作用,且能显著降低墨汁推进的速率,有较好的抗腹泻作用。结论:刹毒草口服液具有一定抗疲劳、抗炎、提高非特异性免疫功能和抗腹泻作用。     

Simultaneous Test for Superiority and Noninferiority Hypotheses in Active-Controlled Clinical Trials∗

The primary objective of the dose-escalation trial for NGX267 was to estimate the maximally tolerated dose (MTD) and to gather detailed clinical and pharmacokinetic observations near the MTD. The MTD was defined based on the weighted average of moderate and severe adverse events. An adaptive design was employed to concentrate dosage assignments at or near the MTD. Favoring the acquisition of data near the MTD, at the expense of information at lower dosage levels, resulted in a shorter trial and no loss of the type of information required to inform subsequent studies where larger normal volunteer or patient samples are evaluated.     

氢溴酸山莨菪碱注射液细菌内毒素检查法的建立

目的:建立氢溴酸山莨菪碱注射液的细菌内毒素检查方法。方法:按《中国药典》2010年版(二部)附录相关方法确定本品细菌内毒素限值,分别进行细菌内毒素检查凝胶法和动态浊度法的干扰试验。结果:凝胶法结果表明,样品稀释2倍(5 mg/ml)时对试验无干扰作用;动态浊度法结果表明,本品稀释2倍(5 mg/ml)时外加内毒素的回收率在50%²00%之间。每1 mg氢溴酸山莨菪碱中含内毒素应小于0.35 EU。结论 :本文初步建立的氢溴酸山莨菪碱注射液细菌内毒素检查方法,可为《中国药典》增订该制剂的细菌内毒素检查项提供参考。     

Bootstrap inference in a linear equation estimated by instrumental variables

Summary We study several tests for the coefficient of the single right‐hand‐side endogenous variable in a linear equation estimated by instrumental variables. We show that writing all the test statistics—Student's t, Anderson–Rubin, the LM statistic of Kleibergen and Moreira (K), and likelihood ratio (LR)—as functions of six random quantities leads to a number of interesting results about the properties of the tests under weak‐instrument asymptotics. We then propose several new procedures for bootstrapping the three non‐exact test statistics and also a new conditional bootstrap version of the LR test. These use more efficient estimates of the parameters of the reduced‐form equation than existing procedures. When the best of these new procedures is used, both the K and conditional bootstrap LR tests have excellent performance under the null. However, power considerations suggest that the latter is probably the method of choice.