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토끼의 수종 점막 추출액중 $[D-Ala^2]-Methionine$ Enkephalinamide의 분해 및 안정화
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  • 토끼의 수종 점막 추출액중 $[D-Ala^2]-Methionine$ Enkephalinamide의 분해 및 안정화
저자명
전인구,양윤정,Chun. In-Koo,Yang. Yoon-Jeong
간행물명
藥劑學會誌
권/호정보
1992년|22권 3호|pp.173-183 (11 pages)
발행정보
한국약제학회
파일정보
정기간행물|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

To study the feasibility of transmucosal delivery of $[D-ala^2]-methionine$ enkephalinamide (YAGFM), its enzymatic degradation and stabilization in various rabbit mucosal extracts were investigated by HPLC method. The degradation of YAGFM was observed to follow the first-order kinetics and the half-lives of YAGFM in the nasal, rectal and vaginal mucosal extracts were found to be 25.7, 3.0 and 7.8 hr, respectively. However, there was no significant difference in degradation rates of YAGFM between the mucosal and serosal extracts obtained from the same mucosal membrane. This finding suggests that even a synthetic enkephalin analog, which is designed to be resistent to aminopeptidases, needs to be fully protected from the enzymatic degradation in mucosal sites for the delivery of the analog through mucosal routes. To inhibit the degradation of YAGFM in various mucosal extracts, effects of enzyme inhibitors such as bestatin (BS), amastatin (AM), thiorphan (TP), thimerosal (TM) and EDTA, alone or in combination, and modified cyclodextrins were observed by assaying YAGFM staying intact during 24 hr-incubation at $37^{circ}C$. It was found from the results that mixed inhibitors such as TM (0.5 mM)/EDTA (5 mM) or AM $(50{mu}M)/TM$ (0.5 mM)/EDTA (5 mM) provided very useful means for the stabilization in various mucosal extracts. The latter was found to protect YAGFM from the degradation in the nasal, rectal, and vaginal mucosal extracts by 90.9, 90.4 and 91.3%, respectively, after 24 hr-incubation, suggesting almost complete inhibition of YAGFM-degrading enzymes present in the incubation mixture. However, BS $(50{mu}M)$, AM 50 $(50{mu}M)$ or TP$(50{mu}M)$ alone did not reveal sufficient inhibition except TM (0.5 mM) or EDTA (5 mM). The adddition of $2-hydroxylpropyl-{eta}-cyclodextrin$(10%) to the nasal mucosal extract, and $dimethyl-{eta}-cyclodextrin$(10%) to the rectal and vaginal mucosal extracts reduced the first-order rate constants for the degradation of YAGFM by 5.8, 17.3 and 8.9 times, respectively, compared to those with no additive.