Izutsu K, Yoshioka S, Terao T
National Institute of Hygienic Sciences, Tokyo, Japan.
Pharm Res. 1993 Aug;10(8):1232-7. doi: 10.1023/a:1018988823116.
The stabilizing effects of various additives against inactivation of an enzyme (beta-galactosidase from Aspergillus oryzae) during freeze-drying were studied, with a focus on their crystallinity. The crystalline morphology of mannitol and inositol in freeze-dried cakes depended on the solute concentrations before freezing and the freeze-drying method used. The additives in their amorphous state showed concentration-dependent stabilization of the enzyme, whereas additive crystallization during freeze-drying decreased their effects. Heat treatment before freeze-drying also caused crystallization and diminished the stabilizing effects. Noncovalent soluble aggregates were observed in the inactivated enzyme solution. These results show the importance of maintaining the amorphous state of additives used as stabilizing agents during freeze-drying.
研究了各种添加剂在冷冻干燥过程中对一种酶（米曲霉β-半乳糖苷酶）失活的稳定作用，重点关注其结晶度。冷冻干燥饼中甘露醇和肌醇的晶体形态取决于冷冻前的溶质浓度和所采用的冷冻干燥方法。处于无定形状态的添加剂对酶表现出浓度依赖性稳定作用，而冷冻干燥过程中添加剂的结晶会降低其效果。冷冻干燥前的热处理也会导致结晶并减弱稳定作用。在失活的酶溶液中观察到非共价可溶性聚集体。这些结果表明在冷冻干燥过程中保持用作稳定剂的添加剂的无定形状态的重要性。
