蝎精酒的质量控制

为了有效地控制蝎精酒的质量,采用薄层层析方法对蝎精酒中的功效性原料进行了定性鉴别,并采用仪器分析的方法对功效原料中的成分牛磺酸和其他氨基酸进行了定量分析.结果使用阳性对照药材进行薄层检测,可以有效地定性鉴别功效原料;6个生产批次样品中牛磺酸的含量为14.792±4.3158(mg/100mL),且在产品中性质稳定;由于牛磺酸用于免疫调节作用的最佳有效剂量为0.1mg/kg,建议蝎精酒的成人1日服用剂量在30～60mL为宜.所以,上述实验方法和指标可以用于蝎精酒的质量控制.     

蝎龙酒治疗糖尿病周围神经病变32例临床疗效分析

目的 观察蝎龙酒治疗糖尿病周围神经病变的临床疗效.方法 64例确诊的糖尿病周围神经病变的患者随机分为治疗组32例和对照组32例,治疗组给予蝎龙酒治疗,对照组每天口服甲钴胺片治疗.结果 治疗组总的有效率为90.6%,高于对照组的71.9%,两组相比有统计学差异(P＜0.05).结论 蝎龙酒能改善糖尿病周围神经病变的微循环和神经传导速度,对糖尿病周围神经病变的治疗是有效的.     

蝎龙酒的制备及其质量标准研究

目的:制备蝎龙酒并建立其质量标准。方法:采用经典冷浸法制备蝎龙酒;采用薄层色谱(TLC)法对方中白芍进行定性鉴别;采用高效液相色谱法对方中活性成分阿魏酸进行含量测定。结果:所制备制剂为棕黄色的澄清液体;TLC斑点清晰,分离度好;阿魏酸检测浓度在3.66～36.64mg·mL-1(r=0.9998)范围内与峰面积积分值呈良好线性关系;平均回收率为100.47%,RSD=0.84%(n=15)。结论:该制剂制备工艺简便可行、质量稳定可控,所建标准可用于蝎龙酒的质量控制。     

药品杂质遗传毒性评价的概述

本文综述了近年来国内外药品杂质遗传毒性评价的进展.药品遗传毒性评价的结果直接关系到药品杂质限度的制定,各种杂质的遗传毒性评价方法的研究进展迅猛,在现阶段条件下,使用计算机预测药品杂质的遗传毒性;探索以γH2AX为代表的生物标志物检测替代传统的体内外遗传毒性检测体系;并使用斑马鱼模式动物对其遗传毒性进行验证是行之有效的杂...     

药物遗传毒性研究的考虑要点

遗传毒性研究是药物非临床安全性评价的重要内容.<药物遗传毒性研究技术指导原则>已于2007年10月发布,本文结合该指导原则的起草修订情况,讨论目前药物遗传毒性研究相关问题的一些考虑要点.     

蝎毒性心肌病

蝎毒性心肌病蝎蜇伤是儿童的常见问题，主要临床表现为兴奋，流涎，出汗呕吐，腹部痉挛，过速性心律失常，高血压和外周血管收缩增强。实验和临床研究表明，蝎毒能直接或通过中枢下丘脑通路刺激肾上腺髓质和交感神经末梢，使其突然释放大量儿茶酚胺，从而引起高血压、外周...     

东亚钳蝎毒素对大鼠实验性大肠癌的抑制作用

前阶段研究证实蝎毒素对体外培养大肠癌细胞有显著抑制作用.为进一步探索其对大肠癌发生发展的影响,利用盐酸二甲基肼诱发Wistar鼠大肠癌的动物模,通过分组、分阶段研究蝎毒素对大肠肿瘤发生过程和组织病理改变的作用.结果发现蝎毒素可以降低诱癌率和诱癌鼠死亡率.20周内单纯诱癌组死亡率达32.6%,蝎毒灌胃组和腹腔注射组分别为23.0%和20.51%,其中蝎毒注射组死亡率与单纯诱癌组相比有显著差异有显著差异(P<0.05).20～31周单纯诱癌组诱癌率为81.82%,蝎毒注射组为44.00%,两组差异显著(P<0.01).大肠癌核仁组成区染色结果发现单纯诱癌组AgNOR颗粒明显增加而蝎毒注射组显著减少,第核AgNOR颗粒数两组有显著差异(P<0.05).结果提示蝎毒素具有去除DMH毒性,降低实验肿瘤的发生,抑制大肠肿瘤细胞rRNA活性,直接抑杀肿瘤细胞的作用.     

药品中遗传毒性杂质的评估和控制

目的 综述药品遗传毒性杂质控制相关指南和法规,为制药企业执行国际标准和准则提供一些建议和思路。方法 通过查找数据库如Pubmed、Medline及欧洲药品管理局(European Medicines Agency,EMA)、美国食品药品监督管理局(US Food and Drug Administratio,U.S.FDA)、人用药品注册技术要求国际协调会议(ICH)等网站,比较各指南法规关于遗传毒性控制限度和控制措施的异同点,为遗传毒性杂质的控制提供一个可行性步骤。结果 通过比较发现,EMA、U.S.FDA和即将出版的ICH M7指南在关键原则的应用方面如毒理学关注阈值(threshold of toxicological concern,TTC)、风险评估步骤、杂质5分类法等基本相同,但现行EMA和U.S.FDA法规存在分歧,不利于其有效执行,而ICH M7将为遗传毒性杂质的控制提供一个可行框架。结论 目前还缺乏完善有效的遗传毒性控制指南,ICH M7将解决U.S.FDA 和EMA 指南间分歧,更好地指导制药企业遗传毒性杂质的控制。     

注射用伏立康唑前药的遗传及生殖毒性研究

目的 研究注射用伏立康唑前药(Voriconazole prodrug,VP)的遗传及生殖毒性.方法 分别采用Ames试验、中国仓鼠肺细胞(CHL)染色体畸变试验、小鼠骨髓微核试验,观察VP的遗传毒性,并通过伴随毒动学试验了解其血浆暴露量;生殖毒性研究了注射用VP对SD大鼠胚胎-胎仔发育毒性的影响,于SD大鼠妊娠第6～ 15天连续iv给药(30、60、120 mg· kg-1·d-1),于妊娠第20天剖检,分析其生殖毒性.结果 遗传毒性的Ames试验、CHL试验和微核试验中,结果均显示为阴性;伴随毒动学试验表明:受试物在小鼠体内呈线性消除;胚胎-胎仔发育毒性试验中,受试物高剂量组中胎鼠头颅骨和/或胸骨异常的数量与溶媒对照组相比显著增加.结论 注射用VP未见明显遗传毒性;受试物在120 mg·kg-1剂量下对胎鼠骨骼发育有一定的毒性作用,未见其他生殖毒性.     

富马酸泰诺福韦双特戊酯的遗传毒性研究

目的 检测富马酸泰诺福韦双特戊酯(TDF)的遗传毒性,为临床用药提供理论依据.方法 应用鼠伤寒沙门细菌回复突变试验(Ames试验)、体外培养中国仓鼠肺成纤维细胞(CHL)细胞染色体畸变试验和小鼠骨髓微核试验检测该药物的遗传毒性.结果 该药物对鼠伤寒沙门菌无致突变性,对体外培养CHL细胞染色体无致畸变作用,对昆明小鼠无诱发骨髓嗜多染红细胞微核的效应,三个试验结果均呈阴性.结论 TDF不具有遗传毒性.     

益母草不同炮制品的小鼠急性毒性实验研究

目的比较鲜益母草、干益母草和酒炙益母草不同炮制品95％乙醇热回流提取物对小鼠的急性毒性大小,探讨益母草炮制减毒原理,优选炮制工艺。方法分别制备鲜益母草、干益母草和酒炙益母草95％乙醇热回流提取物,按照经典急性毒性实验方法,进行益母草不同炮制品的急性毒性实验研究,实验数据用Bliss法计算LD50.结果益母草不同炮制品对小鼠急性毒性强度以鲜益母草毒性最大,干益母草次之,酒炙益母草毒性最低。鲜益母草和干益母草95％乙醇热回流提取物LD。按含生药量计算分别为83．089g·kg^-1和102．93g·kg^-1,相当于每公斤人日用生药量的145．4倍和240．2倍;95％可信限分别为71．302～97．055g·kg^-1和91．862～115．140g·kg^-1,相当于每公斤人日用生药量的124．8～169．9倍和214．4～268．7倍。酒炙益母草95％乙醇热回流提取物无法作出LD50,MTD实验结果按含生药量计算为98．0g·kg^-1,相当于临床70kg人每公斤体重日用量的228．7倍。结论炮制可降低益母草的毒性,不同炮制方法的减毒作用有差异,通过比较研究有利于实现饮片规范化、标准化,为临床用药提供安全标准和可控依据。     

A celebration of wine: wine IS medicine

Wine describes a diverse commodity class composed of the yeast fermentation products of the must, or juice, pressed from grapes, the fruit of genus Vitis, but both in animal and human studies, wine demonstrates beneficial properties that are independent from the presence of alcohol. These benefits for health are mostly associated with polyphenols, and are absorbable from wine but poorly from unfermented grape juice. Dealcoholised wine is providing all the benefits without the toxicity, and is very affordable; improvements in the organoleptic quality of dealcoholised wine(s) as well as massive distribution are current challenges.     

Supply and demand for alcohol in Australia: relationships between industry structures, regulation and the marketplace

Aspects of alcohol supply and demand relationships are examined in relation to the two main beverage varieties in Australia, wine and beer. It is argued that this case study illustrates how the 'supply side' is able to create and protect demand for alcohol through both taking advantage of and influencing government regulation of the market for alcohol. In relation to low alcohol beer the impact on public health and safety has been extremely positive. In relation to the creation of cask wine in the late 1960s there have been demonstrably deleterious effects. Preferential taxation arrangements for the Australian wine industry have dramatically increased both exports and home consumption. One unintended consequence has been the creation of a major new market for cheap bulk wines that have had a devastating public health impact, particularly on Aboriginal communities, and also the invention of 'alco-pops'. Two-thirds of all table wine consumed in Australia now comes in a cask and 90% of this product is manufactured by three multi-national companies that wield enormous power and political influence to maintain the status quo. The Australian beer industry is well known internationally for its export of 'full strength' (around 5% by volume) beers. What is less well known is its commercial success in the development of low and mid-strength varieties for home consumption. In some States these now comprise 40% by volume of the beer market. This development can largely be attributed to State taxation arrangements, to drink-driving law enforcement, marketing strategies and to a decade of intense competition between several major brewers. This case study indicates how alcohol taxation policy can have major impacts on public health (both positive and negative) but that in a modern market economy it is difficult for governments to act in the public interest due to pressures from vested interest groups.     

新型抗体类药物的临床前安全性评价策略和案例

抗体偶联药物、双特异性抗体等新型抗体已成为近年来抗体工程领域的研究热点,由于其具有特异性高、选择性强和非细胞毒性等优点,在肿瘤治疗领域中具有广阔的应用前景。但该类药物结构和功能相对复杂,给安全性带来特殊风险。在临床前安全性评价中,需要根据其特点和可能介导的毒性作用机制,建立科学的评价方案。通过对新型抗体类药物的类型、结构特点、作用方式以及主要的毒性风险进行综述,并结合已批准的新型抗体类药物的非临床安全性评价实例,探索新型抗体类药物的临床前安全性评价策略。     

SUBULEX: Substance Use Lexicon

In spite of declared intentions to maintain control of drinking, we have cues that during the symposium enough wine was ingested to get intoxicated. Hence, it was widely debated how much wine could be safety drunk, and the conclusion was that it was a matter of individual endurance. Apparently, elders were less prone to wine-induced loss of rationality and control. In conclusion, the Ancients were aware of potential dangers of wine and that its consumption needed rules, but apparently these rules existed for being broken.     

Overview of epidemiological studies on wine, health and mortality

Numerous epidemiological studies have observed that moderate intake of alcohol including wine is associated with a lower risk of cardiovascular disease (CVD). However, according to several authors, moderate consumption of wine is more beneficial than that of beer or spirits. Some studies have shown that moderate consumption of wine can lower mortality from CVD and other causes. The link between drinking wine and total mortality risk (all causes combined) has been studied. The results of various prospective population studies show that intake of beer and spirits from abstention to light to moderate daily intake did not influence mortality, while wine seems to have a beneficial effect on all causes of mortality. Other studies have reached the same conclusion. In general, several authors have reported that in subjects consuming wine in moderation the risk of mortality from all causes is 20-30% lower than in abstainers. Grape wine appears to be the main alcoholic beverage that contains antioxidant phenolic substances known to inhibit oxidation of low-density lipoprotein and affect hemostasis and carcinogenesis. In conclusion, there are differences in the effects of wine, beer and spirits on health. These differences may not be significant in coronary heart disease. Only moderate wine consumption appears to have a beneficial effect on several types of cancer and on total mortality.     

Metabolites and safety: What are the concerns, and how should we address them?

The issue of the safety of drug metabolites in humans is a complex one. In this commentary, a proposal is made regarding how to deal with drug metabolites observed in humans such that the safety of these molecules can be assured. The human radiolabeled ADME study, in which metabolites are identified and quantified in circulation and excreta, is proposed as the primary source of information on human metabolites from which decisions can be made regarding the need for further risk assessment. Although radiolabel ADME studies yield quantitative metabolite profiles that are commonly reported as a percentage of the total drug related material (for circulating metabolites) and a percentage of total dose (for excretory metabolites), it is essential to convert these values into absolute abundances. The structure of a metabolite, its abundance, the biofluid in which it is observed (circulation or excreta), and the toxicity mechanism of concern serve as the four most important characteristics for determination as to whether further safety consideration is warranted. Metabolites in circulation require consideration for toxicity that can arise by effects on specific receptors and/or enzymes (either target or off-target). Metabolites in excreta require consideration for their potential to indicate a body-burden to chemically reactive intermediary metabolites, which can yield toxicities of nonspecific mechanisms commonly associated with covalent binding (e.g., carcinogenicity, immunoallergic response, etc.). Through an analysis of 24 drugs removed from the market because of human toxicity, it was concluded that further testing of human metabolites would not have yielded any additional information that could have predicted human safety findings because human metabolites would have been present in the animal species routinely used in toxicology testing after the administration of the parent compound.     

The cultural history of wine - theoretical background to wine therapy

The knowledge of grape and wine is as old as the cultural history of mankind. Moderate consumption of wine can be beneficial in healthy individuals. It is also known from ancient times that it can cause acute and chronic damage when consumed in great quantities. The disinfectant effect of its use in ointments has been observed already in the antiquity. Polyphenols, among them resveratrol, have generated a great amount of scientific research due to their in vivo and in vitro antioxidant capabilities. For decades, red wine was thought to have beneficial effects on cardiovascular health. This relation was clearly established in the French Paradox phenomenon as well as in the Mediterranean diet. The French Paradox is defined as a low incidence of coronary heart disease, while consuming a diet rich in saturated fat. The cause of this phenomenon is the usually wine drinking in small quantity, supposingly in the consequence of polypenols in red wine. The use of ointments containing polyphenols of wine and the cosmetic treatments with them can be advantageous in the treatment and prevention of some diseases of the skin and the joints, due to its free radical scavenging effect. In healthy individuals the consumption of a moderate amount of 1 to 2 dl wine a day may reduce the mortality of cardiovascular diseases. However, also this quantity can be associated with detrimental effects in pregnant women, in children and in patients with various organic, particularly hepatic, diseases as well as in case of regular administration of certain medicines.     

EPR evaluation of the antiradical activity of wines containing high concentrations of resveratrol

The ability of two samples of red wine with different resveratrol concentrations to inhibit hydroxyl radicals (*OH) produced by a Fenton-type reaction was assessed using the method of electronic paramagnetic resonance (EPR). One sample was an autochthonous wine, Uvalino, which has a very high resveratrol concentration; the second was another red wine with a much lower resveratrol concentration. The ability of the sample of Uvalino wine to obstruct hydroxyl radicals was evident, but it wasn't much better than the ability of the sample of wine with a lower resveratrol concentration. The resveratrol concentration of wine is an important factor for the inhibition of the formation of free radicals, especially hydroxyl radicals; however, it is not the only one responsible for this property of wine. Resveratrol concentration can act synergically with other factors, such as polyphenols, which are also contained in wine and have antioxidant properties.     

Toxicological risks of Chinese herbs

As traditional Chinese medicine (TCM) has become more popular there have been increasing concerns about safety and potential toxicity of the Chinese materia medica (CMM) comprising plants, animal parts and minerals. The potential toxicity of many CMM is well recognised in TCM and to reduce risks use of some herbs is restricted whilst specific processing methods have been developed to modify the activities/toxicity of others. However adverse reactions have been reported, many of these are due misuse or abuse of Chinese medicine. The main problem remains products adulterated with pharmaceuticals for weight loss or erectile dysfunction. But some herbs have narrow therapeutic ranges (e.g., Aconitum species) so toxic effects are frequently reported. Toxic effects from chronic or cumulative dosing are difficult to detect in the traditional setting and recent reports have demonstrated the health problems from Aristolochia species. Despite safety concerns, Chinese medicine appears to be relatively safe with comparatively few reports of adverse reactions compared with overall drug reports. The wealth of information in the Chinese literature needs to be more widely available. As TCM is widely used by patients, improved pharmacovigilance and pharmacoepidemiology can contribute valuable safety information, relevant to clinical use.