新药研制方略
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    Drug development strategies

    Several strategies have been used in the development of new drugs. Over the years all have had success but no single approach has been consistently successful.

    新药研制方略

    近年来,几种方略被用于新药的研发,他们均取得了成功,但没有哪种方法是长盛不衰的。

    Serendipity, luck and intuition.

    偶然发现、运气及直觉

    This approach has been applied less frequently in recent years. The discovery of penicillin by Fleming was in this category.

    此法近年来应用较少。弗莱明发明青霉素属于此类

    Molecular roulette.

    Random chemical synthesis of new structures and pharmacological screening. This approach is wasteful and depends on the availability of sensitive animal or in-vitro models of human disease, which often do not exist.

    分子轮盘赌。

    对新结构式及药理筛选的随机化学合成。此法耗费巨大,且有赖于得到往往很难得到的可利用的敏感型动物或人类疾病的体外模型。

    Minor structural changes in existing agents.

    Occasionally this leads to compounds of greater efficacy and rarely to drugs with novel actions detected in pharmacological screening or clinical practice.

    对现有药物分子结构的修饰。此法偶尔可产生功效更高的化合物,但罕有可能产生药理筛选和临床实践中被检测出具有全新功效的药物。

    Programmed basic research with synthesis of specific chemical.

    Intellectually this approach is the most satisfying. There have been spectacular results, e.g. levodopa and dopamine agonists in the treatment of Parkinsonism; beta-receptor blockers for angina; histamine (H2) antagonists in peptic ulcer disease; converting enzyme inhibitors in hypertension. However, this approach is expensive and there is no guarantee of success.

    针对特定化学物质合成而制定的有计划的基础研究。

    从研究的角度看,这种方法最为令人满意,至今已取得显著成功,例如:治疗帕金森神经功能障碍所用的左旋多巴及多巴胺;治疗心绞痛的肾上腺素受体阻滞剂;消化性溃疡病使用的组胺拮抗药;用于高血压的转换酶抑制剂。不过,此法耗费巨大,且前景莫测。

    Clinical observation of drug action in practice.

    This is the traditional means of drug assessment. New applications arise from measurement of drug action in man in disease states. The antihypertensive effects of thiazide diuretics and beta-blockers were not predicted from animal screening tests. They were only identified after the drugs were available and were being used in practice.

    使用中药物作用的临床观察。

    这是药物评估的传统方法。通过对人体处于疾患状态中药物作用的评估,人们发现其有新的应用价值。噻嗪类利尿剂的抗高血压作用在动物检涵试验中并没发现而是在这些药物投放市场并被实际应用后,其上述作用才被发现。


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