Nielsen L S, Weibel H, Johansen M, Larsen C
Royal Danish School of Pharmacy, Department of Pharmaceutics, Copenhagen.
Acta Pharm Nord. 1992;4(1):23-30.
Endo-dextranase-mediated depolymerization of dextran and dextran derivatives under various experimental conditions in vitro was determined. By a simultaneous determination of Mn and MW of dextrans treated with the enzyme in aqueous buffer, an initial increase of the polydispersity of the polysaccharide sample was observed, indicating that dextranase cleaved the dextran molecules into chains which differed significantly in length. A pH optimum of 5 for the enzyme action was found. However, in the pH range 5-8, which prevails in the colon, the initial depolymerization rates differed by a factor of less than 2. Dextranase treatment of a dextran sample resulted in a constant increase of the concentration of terminal reducing glucose residues per time unit suggesting, that the initial depolymerization reaction followed zero-order kinetics. For degrees of substitution below 12 the efficacy of dextranase fragmentation of dextran conjugates decreased almost linearly with increasing DS. The chemical nature of the attached drug did not significantly affect the depolymerization rates. Maximally depolymerized dextran derivatives were obtained by the combined action of dextranase and various alpha-glucosidases. Treatment of such solutions with: a) model esterases b) 80% plasma and c) 20% liver homogenate did not give rise to an acceleration of the initial drug regeneration, as compared to identical experiments carried out in pure buffer solution (pH 7.4 and 37 degrees C).
测定了体外各种实验条件下内切葡聚糖酶介导的葡聚糖和葡聚糖衍生物的解聚情况。通过同时测定在水性缓冲液中用该酶处理的葡聚糖的Mn和MW，观察到多糖样品的多分散性最初增加，这表明葡聚糖酶将葡聚糖分子切割成长度差异显著的链。发现该酶作用的最适pH为5。然而，在结肠中占主导的pH范围5 - 8内，初始解聚速率相差不到2倍。用葡聚糖酶处理葡聚糖样品导致单位时间内末端还原性葡萄糖残基浓度持续增加，这表明初始解聚反应遵循零级动力学。对于取代度低于12的情况，葡聚糖缀合物的葡聚糖酶片段化效率几乎随取代度（DS）增加呈线性下降。连接药物的化学性质对解聚速率没有显著影响。通过葡聚糖酶和各种α - 葡萄糖苷酶的联合作用获得了最大程度解聚的葡聚糖衍生物。与在纯缓冲溶液（pH 7.4和37℃）中进行的相同实验相比，用以下物质处理此类溶液：a）模型酯酶b）80%血浆和c）20%肝脏匀浆，并未加速初始药物再生。
