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不是通常的嫌疑人:生物制药品的替代表面活性剂
Sebastian Brosig1, Stefano Cucuzza1, Tim Serno1
1Novartis Pharma AG, GDD, TRD Biologics & CGT, Basel CH-4002, Switzerland.
ACS applied materials & interfaces
|July 14, 2023
概括
与传统的多酸盐相比,新的表面活性剂VEDG-2.2和VEDS为生物疗法提供了更好的稳定性. 这些新型的α-托科菲罗尔衍生物减少了蛋白质的聚合和降解,提高了药物的安全性和有效性.
科学领域:
- 生物制药配方 生物制药配方
- 蛋白质的聚合和稳定.
- 表面活性剂化学 表面活性剂化学
背景情况:
- 治疗性蛋白质可以聚集在接口上,导致活性和免疫性丧失.
- 目前的生物疗法依赖于有限的表面活性剂,如聚酸盐 (PS20/80) 和波洛克萨默188,它们有降解和杂质问题.
- 这些问题增加了颗粒生成,蛋白质降解和不良免疫反应的风险.
研究的目的:
- 识别和选用于生物治疗的替代表面活性剂.
- 评估表面活性剂在防止蛋白质聚合和降解方面的有效性.
- 评估候选表面活性剂的化学和酶稳定性.
主要方法:
- 在四种蛋白质模式和六种配方中选了40种替代表面活性剂候选物.
- 采用了三门选过程,包括激发诱导的聚合,粒子分析和表面张力测量.
- 进行了长期稳定性研究,评估了蛋白质纯度和颗粒形成,随后进行了降解倾向分析.
主要成果:
- 确定了新型的α-托科菲罗尔衍生物,VEDG-2.2和VEDS,作为有前途的替代表面活性剂.
- 这些候选物体的蛋白质稳定性与聚酸盐相当或优于聚酸盐.
- VEDG-2.2和VEDS表现出对化学和酶降解的增强抵抗力.
结论:
- 在生物治疗中,VEDG-2.2和VEDS是当前表面活性剂的有价值替代品.
- 这些新型表面活性剂提供了更好的稳定性和降低了降解,减轻了与蛋白质聚合相关的风险.
- 这些发现支持开发更安全,更有效的生物制药配方.
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