Yoshida M, Asano M, Kumakura M, Katakai R, Mashimo T, Yuasa H, Imai K, Yamanaka H
Department of Development, Takasaki Radiation Chemistry Research Establishment, Japan.
J Biomed Mater Res. 1990 Sep;24(9):1173-84. doi: 10.1002/jbm.820240904.
Sequential polydepsipeptides containing both peptide and ester bonds, poly[(L-alanyl)n-gamma-ethyl L-glutamyl-L-lactyl] (n = 0, 1, 2, and 3) (poly[(Ala)n-Glu(OEt)-Lac]), were prepared for application as biodegradable carriers for drug delivery systems. The in vivo degradation of these polymers was evaluated by subcutaneous implantation in the backs of male rats, and was strongly influenced by the number (n) of Ala units in poly[(Ala)n-Glu(OEt)-Lac]. The resulting poly(Ala-Ala-Glu(OEt)-Lac) gave the highest degradability, in which 100% degradation was observed 24 weeks from the start of implantation. A luteinizing-hormone-releasing hormone agonist des-Gly10-[D-Leu6]-LH-RH ethylamide (LH-RH agonist), was incorporated into a sequential poly(Ala-Ala-Glu(OEt)-Lac) carrier by the melt-pressing technique, which gave fine cylindrical polymer formulations with different structures of drug dispersion, e.g., blend-type and sandwich-type formulations. The rate of in vivo release of LH-RH agonist from a blend-type formulation showed a linear decrease with time until its release was finished after 6 weeks' implantation. In contrast, in a sandwich-type formulation, the in vivo release rate was apparently maintained constant over a period of 16 weeks (24 +/- 14 micrograms/day).
制备了同时含有肽键和酯键的序列型聚多肽，聚[（L-丙氨酰）n-γ-乙基-L-谷氨酰-L-丙酯]（n = 0、1、2和3）（聚[（丙氨酸）n-谷氨酸乙酯-L-丙酯]），用作药物递送系统的可生物降解载体。通过在雄性大鼠背部皮下植入来评估这些聚合物的体内降解情况，其降解受到聚[（丙氨酸）n-谷氨酸乙酯-L-丙酯]中丙氨酸单元数量（n）的强烈影响。所得的聚（丙氨酸-丙氨酸-谷氨酸乙酯-L-丙酯）具有最高的降解性，从植入开始24周后观察到100%降解。采用熔融压制技术将促黄体激素释放激素激动剂去甘氨酸10-[D-亮氨酸6]-LH-RH乙酰胺（LH-RH激动剂）掺入序列型聚（丙氨酸-丙氨酸-谷氨酸乙酯-L-丙酯）载体中，得到了具有不同药物分散结构的精细圆柱形聚合物制剂，例如共混型和三明治型制剂。LH-RH激动剂从共混型制剂中的体内释放速率随时间呈线性下降，直至植入6周后释放结束。相比之下，在三明治型制剂中，体内释放速率在16周内（24±14微克/天）明显保持恒定。
