摘要
目的研究添加剂对蛋白质在喷雾干燥过程中的稳定机制。方法以乳糖或甘露醇作为赋形剂,并以聚山梨酯20、十二烷基硫酸钠、L-赖氨酸、羟丙基甲基纤维素或羟丙基-β-环糊精为添加剂将干扰素α-2b制成喷雾干燥粉末。用X光电子能谱分析研究干扰素α-2b的表面吸附现象,用圆二色谱测定该蛋白的二级结构。结果上述几种添加剂均能降低干扰素的表面吸附量;当以乳糖(而非甘露醇)为赋形剂时,添加剂的加入提高了该蛋白α螺旋结构的含量。结论蛋白质在喷雾干燥过程中的稳定性受载体结晶、表面富集和构象变化等多种机制影响。
Abstract
OBJECTIVE To investigate the mechanism of protein stabilization by additives during spray-drying.METHODS Recombinant human interferon α-2b(IFN α-2b) was spray dried,with lactose or mannitol as vehicles and Tween 20,SDS,L-lysine,HPMC and HP-β-CD as additives.X-ray photoelectron spectroscopic analyses were performed to investigate the surface adsorption of IFN α-2b,and the secondary structure of the protein in these formulations was characterized using circular dichroism.RESULTS All of the additives decreased the amount of IFN α-2b on the surface.The inclusion of the additives raised the α-helix content when lactose,but not mannitol,was used as vehicles.CONCLUSION The stability of the protein during spray drying was affected by crystallization,surface adsorption and conformation transformation.
关键词
干扰素α-2b /
喷雾干燥 /
表面吸附 /
结晶 /
α螺旋
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Key words
interferon α-2b /
spray-drying /
surface adsorption /
crystallization /
α-helix
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江荣高;王立青;王春龙;刘衡.
添加剂对喷雾干燥干扰素α-2b稳定机制的研究[J]. 中国药学杂志, 2008, 43(11): 841-843
JING Rong-go;WNG Li-qing;WNG Chun-long;LIU Heng.
Mechanism of Recombinant Human Interferon α-2b Stabilization by Additives During Spray-Drying [J]. Chinese Pharmaceutical Journal, 2008, 43(11): 841-843
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参考文献
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[5] WEBB S D，CLELAND J L，CARPENTER J F，et al.A new mechanism for decreasing aggregation of recombinant human interferon-γ by a surfactant： Slowed dissolution of lyophilized formulations in a solution containing 0.03% polysorbate 20[J] .J Pharm Sci，2002，91 (2)：543-558.
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脚注
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