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Macromolecular drug delivery를 위한 microsphere 및 reservoir형 정제

Title
Macromolecular drug delivery를 위한 microsphere 및 reservoir형 정제
Other Titles
Macromolecular Drug Delivery Systems of Microsphere and Reservoir Type Tablet
Authors
정경림
Issue Date
1991
Department/Major
대학원 약학과
Keywords
Macromolecular drug deliverymicrospherereservoir
Publisher
이화여자대학교 대학원
Degree
Master
Abstract
최근에 개발된 치료효과가 큰 내인성 생리 활성 물질들은 대부분 폴리펩타이드나 프로테인과 같은 macromolecule약물로서, 위장관에서 쉽게 분해되고 불활성화되며 주사제로 적용시 생물학적 반감기기 매우 짧아 정밀한 조절 방출이 요구된다. 이러한 요구에 부응하여, macromolecule약물의 모델로서 우혈청 알부민(BAS)을 선정하여, 생체이식용 alginate moirosphere와 polyurethane으로 코팅된 lactose tablet을 제조하였으며, 약물의 조절방출과 방출메카니즘에 대해 조사하였다. Alginate microsphere의 입자도는 교반속도, 유화시간, 분산매의 조성, 계면활성제의 농도에 의해 조절되었으며, PEG의 이용으로 BAS의 방출속도가 증가되었다. 그리고 microsphere표면의 가교에 의하여 BSA의 방출이 감소되었으며, 최외각에 polymethacrylic acid 방출 조절막을 형성시켜, 방출패턴을 first order에서 zero order로 변화시켰다. 한편 lactose tablet에 polyurethane을 코팅함으로써 osmotic control을 받는 zero order방출패턴을 얻었고, PEG와 PPG를 방출 조절제로 polyurethane membrane에 혼입하여 방출 속도를 증가 시켰다. PEG의 분산을 위하여 pluronic F127을 사용하였을 때, continuous channel을 형성함으로써 방출속도를 더욱 증가시켰다.;For the purpose of developement of long-term implantable DDS of macromolecules, BSA was selected as a Macromolecular model drug and alginate microsphere and polyurethane coated lactose tablet were prepared. The aims of this study were release rate control of BSA and investigation of their release mechanism. The size of alginate microsphere could be controlled by stirring rate, emulsifying time, organic phase composition and surfactant concentration. The albumin permeation rate could be controlled by using PEG and crosslinking of microsphere surface. And the rate limiting outer layer membeane provided zero order release. By polyurethane coating of lactose tablet, bovine serum albumin release was controlled by osmotic pumping mechanism and the pattern of bovine serum albumin release was zero order. Adding PEG and PPG in polyurethane coating solution resulted in increasing release rate of bovine serum albumin. By the use of pluronic F 127 as dispersing agent of PEG in polyurethane membrane, continuous channel was formed and release rate was more increased. After all, release rate of BSA could be controlled and zero order release was obtained. So, application of these systems as long-term implantable DDS were expected.
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일반대학원 > 생명·약학부 > Theses_Master
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