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마약길항제의 서방성제제를 위한 생체분해성 Polyphosphazenes의 합성과 응용

Title
마약길항제의 서방성제제를 위한 생체분해성 Polyphosphazenes의 합성과 응용
Other Titles
SYNTHESIS AND APPLICATION OF BIODEGRADABLE POLYPHOSPHAZENES FOR THE NARCOTIC ANTAGONIST SUSTAINED RELEASE SYSTEM
Authors
朴珠愛
Issue Date
1993
Department/Major
대학원 약학과
Keywords
마약길항제서방성제제생체분해성Polyphosphazenes
Publisher
이화여자대학교 대학원
Degree
Master
Advisors
김길수
Abstract
지속시간이 짧고 환자의 compliance가 낮은 마약길항제의 효과적인 투여를 위하여 생체분해성 고분자를 이용한 서방성 제제를 사용하는 것이 바람직하다. 본 연구에서는 서방성 이식제로 사용이 가능한 생체분해성 Polyphosphazene을 합성하고 그 응용성을 검토하고자 하였다. 이를위하여 Poly[dichlorophosphazene]을 용액증합법으로 합성한 후 IR spectrum으로 확인하고 치환기를 바꾸어 생체분해성 고분자로 알려진 Poly[(amino acid alkyl esters)phosphazene]류인 Poly[bis(ethyl glycinate) phosphazene]과 Poly[(diethyl glutamate) -co- (ethyl glycinate) phosphazene]을 합성하였다. 그리고 합성된 고분자를 matrix로 하여 Naloxone hydrochloride를 각각 1%, 3%, 5% 함유한 두께 1㎜, 크기 10×10 ㎜의 device를 제조하고 용출속도와 분해속도를 측정하였다. 팽윤성을 갖는 Poly[bis(ethyl glycinate)phosphazene]의 경우에는 분해속도가 용출속도보다 느린것으로 보아 용출속도는 팽윤속도에 의하여 결정됨을 알 수 있었다. 그러나, Poly [(diethyl glutamate)-co-(ethyl glycinate)phosphazene]에서는 제제의 분해속도와 Naloxone Hydrochloride의 용출속도가 일치하므로 마약길항제 서방성 이식정에의 응용이 가능할 것으로 기대된다.;For the administration of narcotic antagonist with short half-life and low patient compliance, the sustained release system using biodegradable matrix is effective. Polyphosphazenes are of considerable interest as biodegradable matrix systems for controlled release of drugs. In this study, biodegradable polyphosphazenes available for the sustained release implantable device were synthesized, and their application was examined. Poly[dichlorophosphazenel was synthesized by solution polymerization method and confirmed with IR spectrum. Poly[bis-(ethyl glycinate)phosphazene] and poly[(diethyl glutamate)-co-(ethyl glycinate)phosphazene] were then produced by substitution of amino acid alkyl esters for chloride side groups. Using these polymers, the implantable devices of 1mm thickness and 10×10mm size containing 1%, 3%, 5% naloxone hydrochloride were prepared and their release and degradation profiles were measured. In the case of poly[bis(ethyl glycinate)phosphazene] with swelling characteristics, degradation rate was slower than the release rate, showing that the release rate is partly dependent on the swelling rate. In contrast, the degradation rate of poly[(diethy1 glutamate)-co-(ethyl glycinate)phosphazene] matrix was identical with release rate of naloxone hydrochloride. On the basis of these results, it is expected that these polymers can be applied to sustained release implantable systems delivering narcotic antagonist.
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