生物降解左旋-18甲长效避孕埋植剂的研制及其体外释放研究

Study on Preparation and Its in Vitro Delivery System of Biodegradable Long-Acting Contraceptive Implant with Levonorgestrel.

生物降解型长效避孕埋植剂是一种可以免除在药物释放完后须经手术将埋植剂取出的、新型的、能恒速释放避孕药的皮下埋植剂。本文报道了以嵌段型聚已内酯丙交酯(CL-b-LA)为载体材料,制备生物降解左旋-18甲长效避孕埋植剂的方法,以及测定其药物含量的方法。同时,详细探讨这种皮下埋植剂体外释放的规律,研究了影响药物释放的各种因素,包括埋植剂载体材料的共聚组成、添加不同固体分散剂、固体分散剂用量和分子量、埋植剂包衣等对LNC药物释放的影响。在上述研究的基础上,选择(?)-已内酯/DL-丙交酯为85/15的嵌段共聚物作为载体材料,研制了三种不同的埋植剂:①载药量为30％;②载药量为50％;③载药量为30％+20％PEG6000。并进行了其体外药物释放的研究。结果表明,这是一种有临床应用前景、能恒速释放左旋-18甲基炔诺酮的长效避孕埋植剂。

Research on the use of biodegradable polymers as a carrier in drug delivery systems has increased rapidly in recent years. Biodegradable long-acting contraceptive implant with levonorgestrel(LNG)is a novel subdermal controlled release system which e-liminate the neccessity for surgical removal of implanted device following depletion of a drug. This paper reports on the preparation of the biodegradable long-acting contraceptive implant using block copoly-mer of e-caprolactone and DL-lactide as drug carrier and determination of LNG loading in the implant. The release behavior of LNG from the implant as well as a various of factors with relation to drug release were investigated, including composition of block copolymer, different solid dispersant, quantity and molecular weight of the dispersant and coating of the implant. According to the above results,the block copolymer of poly (e-caprolactone-b-DL lactide),[P (CL-b-DLLA)], with a content of poly (e-caprolactone )fixed at 85% have been used for carrier material and three kinds of implant have been prepared,i. e:(1) 30% of drug loading; (2)30% of drug loading with 20% of polyethylene glycol (Mw: 6 000); (3) 50% of drug loading. The in vitro release behavior of these implants have been also conducted in this study. The results showed that the implant with LNG prepared from the block copolymer of P (CL-b-DLLA ) may serve as a new type of biodegradable long-acting contraceptive implant with constant release of the pro-gestogen.