Fukuzaki H, Yoshida M, Asano M, Kumakura M, Mashimo T, Yuasa H, Imai K, Yamanaka H
Department of Development, Takasaki Radiation Chemistry Research Establishment, Japan Atomic Energy Research Institute, Gumma, Japan.
Biomaterials. 1990 Aug;11(6):441-6. doi: 10.1016/0142-9612(90)90102-v.
Low molecular weight and amorphous copolyesters composed of 70 mol% L-lactic acid and 30 mol% DL-hydroxy acids such as DL-lactic acid, DL-alpha-hydroxy-n-butyric acid, DL-alpha-hydroxyisovaleric acid and DL-alpha-hydroxyisocaproic acid were synthesized by direct copolycondensation in the absence of catalysts, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. For this purpose, the copolyester was moulded into a small cylindrical specimen under melt-pressing technique and implanted subcutaneously in the back of male adult rats. The in vivo degradation pattern can be subdivided into three types: the formations of parabolic type (L-LA/DL-HBA copolymer), linear type (L-LA/DL-LA copolymer) and S type (L-LA/DL-HIVA and L-LA/DL-HICA copolymers). A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide monoacetate (LH-RH agonist), was incorporated into the small cylinders of copolyester formulations, of which the strongest pharmacological influence was observed in a copoly(L-LA/DL-HICA) formulation system, resulting in the maintenance of effective pharmacological influence throughout an experimental period of 15 wk, at which the in vivo release rate of LH-RH agonist was held constant at approximately 45 micrograms/d.
通过在无催化剂条件下直接共缩聚反应，合成了由70摩尔%的L-乳酸和30摩尔%的DL-羟基酸（如DL-乳酸、DL-α-羟基正丁酸、DL-α-羟基异戊酸和DL-α-羟基异己酸）组成的低分子量无定形共聚酯，以评估它们作为药物递送系统的可生物降解载体的体内性能。为此，将该共聚酯在熔融压制技术下模塑成小圆柱形试样，并皮下植入成年雄性大鼠背部。体内降解模式可分为三种类型：抛物线型（L-LA/DL-HBA共聚物）、线性型（L-LA/DL-LA共聚物）和S型（L-LA/DL-HIVA和L-LA/DL-HICA共聚物）。将一种促黄体生成素释放激素激动剂，去甘氨酸10-（D-亮氨酸6）-LH-RH乙酰胺单乙酸盐（LH-RH激动剂），掺入共聚酯制剂的小圆柱体中，其中在共聚物（L-LA/DL-HICA）制剂系统中观察到最强的药理作用，在整个长达15周的实验期内维持有效的药理作用，在此期间LH-RH激动剂的体内释放速率保持恒定，约为45微克/天。
