황체호르몬 유리호르몬의 경점막 수송: 수종의 흡수촉진제를 사용한 [D-Ala6] LHRH의 점막투과촉진 및 흰쥐에 있어서의 배란유도효과 향상

Transmucosal Delivery of Luteinizing Hormone Releasing Hormone(LHRH): Evaluation of Membrane Permeability Enhancement of [D-Ala6] LHRH in Rabbit Mucosa and Ovulation Inducing Effect in Vaginal Administration of Rat by the Addition of Several Ab

Due to the limited bioavailability of [D-Ala6] LHRH from nonparenteral transmucosal sites of administration, enhancement of mucosal permeability by coadministration of several protease inhibitors and/or penetration enhancers were studied in rabbit mucosa. As a reliable bioassay method for [D-Ala6]LHRH, ovulation-inducing effect were measured after vaginal administration in the rat. The permeation of [D-Ala6]LHRH through the mucosal membrane of rabbit mounted on George-Grass diffusion cells were examined in the presence of polyoxyethylene 9-lauryl ether (POE), beta-cyclodextrin(beta-CyD) or ethylene diamine tetra acetate disodium salt(EDTA). The vaginal membrane showed higher permeability of [D-Ala6]LHRH than the rectal and nasal membrane. POE and beta-CyD showed a small promoting effect on the membrane permeation of [D-Ala6]LHRH, but EDTA showed significant enhancement. Ovaluation was enhanced by the coadministration of sodium laurate(O.5%), a protease inhibitor but was not enhanced by EDTA, a penetration enhancer. On the other hands, coadministration of sodium tauro 24,25 dihydrofusidate(l%) and EDTA(2%) enhanced the ovulation inducing-effect 2.8 times. These results suggest that the vaginal administration of [D-Ala6]LHRH with STDHF or sodium laurate as a protease inhibitor, and EDTA as a penetration enhancer, may become an effective method for transmucosal delivery of [D-Ala6]LHRH.