Bauguess C T, Sadik F, Fincher J H, Hartman C W
J Pharm Sci. 1975 Jan;64(1):117-20. doi: 10.1002/jps.2600640125.
A series of fatty acid esters of acetaminophen were prepared beginning with acetate, the propionate, and all even-numbered fatty acids and going through the octadecanoate. The enzymatic hydrolysis of all derivatives was studied in vitro with varying amounts of lipase assed to the hydrolysis mixtures. Under the conditions of the in vitro hydrolysis, it was observed that all derivatives were hydrolyzed more readily in an aqueous medium at pH 7.8. A positive relationship was seen between the hydrolysis rates and the concentration of lipase at this pH. There was a negative relationship between the chain length of the acyl moiety and the corresponding hydrolysis rates. The short chain esters were hydrolyzed at rates many times more rapid than the long chain esters. The intermediate chain-lenght ester, p-acetamidophenyl decanoate, p-acetamidophenyl laurate, and p-acetamidophenyl myristate, were hydrolyzed at intermedediate time periods extending over 12 hr, approaching completion at 97.5, 87.5, and 80.5%, respectively, when 18 Wilson units of lipase was used in each milliliter of hydrolysis mixture. The longer chain esters, p-acetamidophenyl palmitate and p-acetamidophenyl stearate, were hydrolyzed to the extent of 16 and 8%, respectively, over 12 hr under the same in vitro conditions.
从乙酸酯开始，制备了一系列对乙酰氨基酚的脂肪酸酯，包括丙酸酯以及所有偶数碳脂肪酸酯，直至十八烷酸酯。使用不同量的脂肪酶添加到水解混合物中，对所有衍生物的酶促水解进行了体外研究。在体外水解条件下，观察到所有衍生物在pH 7.8的水性介质中更容易水解。在此pH值下，水解速率与脂肪酶浓度之间呈正相关。酰基部分的链长与相应的水解速率之间呈负相关。短链酯的水解速率比长链酯快许多倍。中间链长的酯，对乙酰氨基苯基癸酸酯、对乙酰氨基苯基月桂酸酯和对乙酰氨基苯基肉豆蔻酸酯，在12小时以上的中间时间段内水解，当每毫升水解混合物中使用18个威尔逊单位的脂肪酶时，分别在97.5%、87.5%和80.5%接近水解完全。较长链的酯，对乙酰氨基苯基棕榈酸酯和对乙酰氨基苯基硬脂酸酯，在相同的体外条件下，12小时内分别水解至16%和8%。
