Townsend M W, DeLuca P P
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
J Pharm Sci. 1990 Dec;79(12):1083-6. doi: 10.1002/jps.2600791209.
The solution stability of bovine pancreatic ribonuclease A (RNase) in phosphate buffer (pH 4.0, 6.4, and 10.0) at 45 degrees C decreased with increasing pH. Soluble aggregates were formed at each pH and corresponded qualitatively to the loss of enzymatic activity in the samples. Freeze drying of RNase resulted in no immediate loss of enzymatic activity in both the presence and absence of phosphate buffer salts. Freeze-dried RNase stored at 45 degrees C lost enzymatic activity and formed nondissociable aggregates at rates described by the following rank order of formulation contents: distilled water less than pH 6.4 phosphate buffer, less than pH 4.0 phosphate buffer less than pH 10.0 phosphate buffer. The amount of residual moisture remaining in the freeze-dried cakes was directly related to the rate of enzymatic activity loss and aggregate formation. The degradation rate was also directly related to the concentration of phosphate buffer salts added to the freeze-dried formulation.
牛胰核糖核酸酶A（RNase）在45℃的磷酸盐缓冲液（pH 4.0、6.4和10.0）中的溶液稳定性随pH值升高而降低。在每个pH值下都会形成可溶性聚集体，并且在质量上与样品中酶活性的丧失相对应。无论有无磷酸盐缓冲盐，RNase的冷冻干燥都不会立即导致酶活性丧失。在45℃下储存的冷冻干燥RNase会丧失酶活性，并以以下制剂含量的降序排列形成不可解离的聚集体：蒸馏水＜pH 6.4磷酸盐缓冲液＜pH 4.0磷酸盐缓冲液＜pH 10.0磷酸盐缓冲液。冷冻干燥饼中残留的水分量与酶活性丧失速率和聚集体形成直接相关。降解速率也与添加到冷冻干燥制剂中的磷酸盐缓冲盐浓度直接相关。
