一致性评价品种选择及评价方式

目前国内原研药在大医院药品销售占比高达80%,仿制药质量参差不齐,提高仿制药质量,临床上实现与原研药相互替代,才能够推动药品生产领域的结构性变革。一致性评价是提升国产仿制药国际竞争力的必由之路。2016年国家食品药品监督管理总局(CFDA)陆续发布了多个一致性评价的技术要求和指导原则,标志着一致性评价进入实质操作阶段。一致性评价工作对于企业既是挑战也是机遇,企业涉及的一致性品种做还是不做,应该做哪些品种?本研究就企业仿制药一致性评价品种如何筛选和评价方式进行探讨。     

生物制药项目价值评估方法研究

目的探讨适合生物制药项目价值评估的方法。方法查阅在生物制药业项目开发阶段的价值评估方法,比较传统的净现值法、风险调整的净现值法以及实物期权法在评估生物制药项目价值中的应用。结果与结论风险调整的净现值法以及实物期权法是较好的研究生物制药项目价值评估的方法。     

An in vivo method for the quantitative evaluation of local anesthetics

We describe a mouse model for evaluation of skin anesthesia after infiltration of local anesthetic. The method involves subcutaneous injection of the anesthetic over the abdomen, and monitoring the vocalization response to electrical stimulus as a measure of analgesia. Prior to drug injection, the vocalization threshold was determined. Mice that vocalized at < or = 8 mA were included in the study. The model was tested using representative agents of the two classes of local anesthetics, bupivacaine, an amide, and chloroprocaine, an ester. The time course and dose response were assessed after injection. The median analgesic time was 15, 40, and 55 min for 0.015%, 0.0625%, and 0.25% bupivacaine and 30, 50, and 55 min for 0.125%, 0.25%, and 2.0% chloroprocaine, respectively. Statistical analysis of the data showed that this method is sufficiently sensitive to detect differences between the dose and duration of local anesthesia (p<0.05, by log rank test of the survival curves). To further validate the model, we compared the duration of anesthesia between the 0.5% bupivacaine and a new long-acting liposomal formulation of 2% bupivacaine. The results showed that the new formulation significantly prolonged the duration of anesthesia (p<0.05). This simple and reliable method may facilitate research on the pharmacology of infiltration anesthesia and the development of new local anesthetics and/or formulations.     

An objective method for the evaluation of eye irritation in vivo

It is generally agreed that intra- and interlaboratory variations in the evaluation of eye irritants are mainly due to the subjective judgement of eye lesions. The scoring of the palpebral conjunctivae is a typical example. To eliminate these difficulties in assessing eye irritants the relationship between corneal swelling, which can be determined using an objective technique, and the reading of other symptoms was investigated. The in vivo eye irritation assay was carried out on 34 substances according to the protocol laid down in Annex V, part B of Directive 79/831/EEC of the European Community on the classification, labelling and packaging of dangerous substances. Results were obtained for erythema, oedema, corneal opacity and corneal swelling. Erythema, oedema and opacity were evaluated according to the interpretation rules laid down in Annex VI, part IID of the EEC Directive 83/467/EEC. Corneal swelling was determined by the ultrasonic pachometer technique. Good correlations were found between the mean percentage corneal swelling after 24, 48 and 72 hr and the mean corneal opacity (r = 0.94) and erythema scores (r = 0.93) after the same observation times. The corneal swelling scores measured after 24 hr using the ultrasonic pachometer are comparable with those reported in the literature, which were obtained by optical pachometry. The good correlation with the other effects scored and the good repeatability of the results opens the possibility of introducing an objective and sensitive method into the ocular irritation assay and so reducing intra- and interlaboratory variations.     

An electromyographic method for the quantitative evaluation of narcotic analgesics in rats

A new electromyographic (EMG) method described by Bieger et al. (1972) was developed for the quantitative evaluation of narcotic analgesics in rats anesthetized with urethane. d-Amphetamine increased the amplitude and the frequency of myoclonic twitch activities (MTA) of suprahyoideal muscle. Morphine and several other narcotic analgesics antagonized the amphetamine-induced MTA and their relative inhibitory potency closely paralleled their analgesic potencies. Etorphine was 2000–3500 times more potent than morphine, while meperidine showed only 2% of the activity of morphine. Levorphanol was 3–4 times more potent than morphine, while dextrorphan was inactive. l-Methadone was 10 times as potent as d-methadone. The inhibition of MTA by morphine was completely reversed by naloxone. On the other hand, the inhibition of MTA by haloperidol or by pentobarbitone was not influenced by naloxone. The measurement of the EMG of suprahyoideal muscle in rats appears to provide a convenient test and reliable means to assess the central effect of narcotic analgesics.     

An alternative method to the evaluation of similarity factor in dissolution testing

This paper addresses an alternative method to the evaluation of similarity factor f₂ as a criterion for assessment of similarity between two in-vitro dissolution profiles as proposed in the SUPAC-IR Guidance (1995). Diltiazem hydrochloride Sustained-Release (SR) tablets were tested and the following independent-model dissolution parameters were used: t_10% dissolution time, t_25% dissolution time, t_50% dissolution time, mean dissolution time (MDT), dissolution efficiency (DE) at t₁₂₀, and at t₃₆₀. To compare the dissolution profiles, several release models were tested such as Higuchi, zero order, first order, Baker-Lonsdale, Hixson-Crowell, Weibull and Korsmeyer-Peppas. The similarities between two in-vitro dissolution profiles were assessed by pair-wise independent-model procedures such as difference factor (f₁), similarity factor (f₂) and Rescigno index (ξ₁ and ξ₂). The in vitro release kinetics of diltiazem hydrochloride sustained release tablets were evaluated using USP apparatus 2.     

类风湿关节炎达标治疗中目标的选择及其评估方法

类风湿关节炎(rheumatoid arthritis,RA)较完整的达标治疗的基本理念形成于2010年。制定明确的目标,是完成达标治疗最关键的步骤。目标的科学性及其易评估性非常重要。达到疾病缓解或维持低疾病活动度(low disease activity,LDA)已成为目前大多数风湿病学者和临床医师认同的RA治疗的目标。2011年美国风湿病学会(American College of Rheumatology,ACR)和欧洲抗风湿病联盟(European League Against Rheumatism,EULAR)联合制定了RA的临床缓解标准,即疼痛关节数、肿胀关节数、C-反应蛋白、患者对疾病的总体评估均<1、简化的疾病活动指数(simplified disease activity index,SDAI)≤3.3。低疾病活动度有不同的标准,疾病活动性评分(disease activity score,DAS),以28个关节评估的疾病活动性评分(28-joint disease activity score,DAS28),SDAI和临床疾病活动性指数(clinical disease activity index,CDAI)等评估体系均能用以评估疾病活动性,每个评估系统的严格与否取决于各自的节点值,什么样的节点值更适合于RA治疗的低疾病活动度的目标有赖于更多的研究提供支持。     

PDG教学法在眼科教学中的应用评价

目的评价PDG教学法在眼科教学中的应用。方法在眼科常见病中选择两个章节,要求学生对这两章的重视程度基本相同,在临床中较为重要且应用相近。其中一章采用传统的教学方法,另一章采用PDG教学法,比较两种教学方法的教学效果。结果应用PDG教学法的一章中,94．7％的学生认为课堂效果非常好．92．1％的学生通过独立思考,提高了学生解决问题的能力。在考试中,两章内容的平均成绩比较,差异有统计学意义（P〈0．05）。结论PDG教学法在眼科教学中受到了教师和学生的好评,增强了学生学习的积极性,使眼科教学效果得到显著提高。     

A modification of a method for the evaluation of topical anaesthesia in the earthworm

The method of Block, Potts & Finney (1964) for the evaluation of local anaesthetic activity using the response of the earthworm tail to hydrochloric acid has been found to give false negative results with control solutions. This was because the acid progressively damaged and thus desensitized the tail. This has been overcome by arranging the test so that no tail is immersed in the acid more than three times during an assay.     

应用NCCLS EP5-A方案评价唾液酸试剂盒的精密度

目的 评价测定唾液酸(SA)试剂盒的精密度.方法 利用NCCLS EP5-A方案评价唾液酸的精密度.结果 正常和异常血清的批内变异系数分别为0.9%和1.9%.批间变异系数分别为1.2%和1·7%,总变异系数为1.6%和2.6%.结论 SA试剂盒精密度良好,准确可靠且操作简便.     

The biometrie evaluation of the acute-toxic-class method (oral)

The acute toxic class method (ATC method) is an alternative to the LD₅₀ test, with the use of substantially fewer animals needed for the classification of substances. Like the classical LD₅₀ test the biometry of the ATC method is based on the probit model. The biometrie calculations of the ATC method were carried out not only for the classification categories of the European Union but also for the classification criteria of various countries and organizations, currently in use. It is demonstrated that in comparison with the LD₅₀ test in general the same classification is obtained with the ATC method and with the use of substantially fewer animals. Substances with high slopes are likely to be allocated to the predicted toxicity class in comparison with substances having low slopes, with both the ATC method and the LD₅₀ test. Substances are more likely to be allocated into a lower toxicity class with the LD₅₀ test than with the ATC method.     

中药安全性评价与监护方法的探讨

目的探索现代医院中药安全性监护方法。方法依据国家颁发的《医院分级管理评判标准》《、中医医院管理评价指南》和《药品不良反应报告和监测管理办法》等技术要求以及有关文献介绍的方法,对中药安全性及监护方法进行初步探讨。结果与结论通过分析中药不良反应的发生机制,旨在建立临床常规监护方法。     

竹节参质量评价方法研究

目的探讨竹节参的质量研究方法。方法采用性状、显微、TLC法对竹节参进行定性鉴别,采用高效液相色谱法测定竹节参皂苷Ⅳa的含量。结果显微观察可见特定组织特征,TLC能检出竹节参皂苷Ⅳa和人参皂苷Ro,HPLC图谱中竹节参皂苷Ⅳa色谱峰与其他色谱峰分离良好,进样量在1.007 6~10.076 0μg范围内呈良好线性关系(r=0.999 9),平均回收率为103.5%,RSD为0.8%(n=6)。结论所建立的方法简便易行,可用于竹节参的质量评价。     

An alternative method for the evaluation of organ weight experiments

Previous work has suggested that the use of relative organ weights can lead to erroneous conclusions in toxicological experiments. A method of analysis involving very little extra experimentation is suggested and evaluated. Simulated results from rat organ weights indicate that the method is superior to the use of relative organ weights and leads to reliable conclusions being drawn about the treatment effects.     

临床药物评价的意义和方法

近年来不断有新药及改变剂型或用途的老药投入临床使用.为了达到临床用药符合安全、有效、经济之目的,临床医生重视并学习临床药物评价的意义及方法是很有必要的.本文简要介绍了有关临床药物评价的概念和药物安全性、有效性、药物经济学、药剂学评价的基本方法.儿科临床药物评价的特点主要在于重视药物在小儿不同发育阶段的疗效与不良反应的差异,以及开展用无痛苦或最小痛苦手段对临床药物进行监测.     

斑马鱼胚胎发育毒性评价方法的建立

目的以致胚胎毒性阳性药物全反式维甲酸（ATRA）及丙戊酸钠进行斑马鱼胚胎发育毒性试验,建立有效的斑马鱼胚胎发育毒性评价方法。方法采用水浴染毒法,将受精后2h（2hpf）的斑马鱼胚胎暴露于不同浓度梯度的阳性约物。分别在24、48、72和144hpf观察并记录畸形及死亡的胚胎数目。统计阳性药物的EC50和LG50,计算致畸指数（TI=LC50／EG50）。结果两种阳性药物所致斑马鱼胚胎发育早期（24～48hpf）与发育后期（72～144hpf）的畸形表现不同。在72hpf,两种阳性药物对胚胎孵化率均有明显抑制作甩144hpf可见ATRA（≥1．6×10^-3mg／L）和丙戊酸钠（≥1．25×10^2mg／L）严晕致畸作用,T1分别为10.35和5．72。两种阳性药物胚胎敛畸率及死亡率均呈明显的浓度依赖关系,且与已有动物试验及体外试验结果相符。结论以两种阳性药物建立有效的斑马鱼胚胎发育毒性评价方法,可进行进一步的验证。