目的 卵泡刺激素(FSH)已成为治疗不孕不育不可或缺的常规药物。笔者通过回顾卵泡刺激素制剂的发展历程,为今后新型卵泡刺激素制剂的开发提供宝贵的经验与教训,也可为其他基因药物的开发提供借鉴。方法 回顾卵泡刺激素制剂的发展历程,对目前所用常规卵泡刺激素制剂生产及质量控制作概述,讨论并分析各制剂的质量问题。结果与结论 安全、有效的卵泡刺激素制剂的开发与应用,充满了来自疗效、安全性以及病人顺应性等各种挑战。动物源性卵泡刺激素的低疗效及免疫源性,人垂体来源卵泡刺激素的安全性,尿源性卵泡刺激素的低纯度等产品质量问题的出现,促进了卵泡刺激素生产工艺的改革,和质量控制技术的完善。重组基因技术的出现,使得具备高纯度、高批间一致性等优点的重组卵泡刺激素得以上市,卵泡刺激素制剂产品走向安全、有效、质量可控,长效卵泡刺激素则进一步改善了病人的用药顺应性。
Abstract
OBJECTIVE Follicle stimulating hormone has been taken as an essential component in the management of infertility. Herein we reviewed the development history of FSH preparations to provide experience and lessons for the research of new FSH preparations, and give an example for the development of other gene medicine.. METHODS The manufacturing techniques and quality control methods of routine FSH preparations were summarized, and the key problems for the preparations were discussed. RESULTS AND CONCLUSION The history of developing safe and effective FSH preparations was full of challenges of efficacy, safety and the patients′ compliance, etc. A series of problems of FSH preparations, such as low efficacy and immunogenicity of animal-sourced FSH preparations, safety of human cadaver FSH, and low purity of urinary FSH, have constantly facilitated both the reformation of manufacturing techniques and improvement of quality control methods of FSH preparations. With the introduction of recombinant DNA technology, recombinant FSH preparations of high purity and consistency are now available, which are safe and effective, and long-acting FSH preparations have improved the compliance of patients.
关键词
卵泡刺激素 /
制剂 /
生产 /
质量控制
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Key words
follicle stimulating hormone /
preparation /
manufacture /
quality control
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参考文献
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脚注
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基金
福建省高校产学合作重大项目(2013N5007)
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