초록 ▼

경구투여용 약물전달체계 개발에 관한 연구에서는 약물을 함유한 소수성고분자 매트릭스 제형을 개발하고 이를 항생제인 cefadroxil에 적용하여 in vitro에서 약물의 방출패턴을 조사하였으며 rat을 이용한 in vivo 약동력학 실험을 실시하였다. 또한 이 매트릭스 제형을 같은 세파계 약물인 cephalexin으로의 응용을 시도하였다. 한편 항암제인 5-Fluorouracil을 model 약물로 하여 ethylene-vinylacetate의 microsphere를 제조하여 표면 및 내면의 SEM Characterization 및

경구투여용 약물전달체계 개발에 관한 연구에서는 약물을 함유한 소수성고분자 매트릭스 제형을 개발하고 이를 항생제인 cefadroxil에 적용하여 in vitro에서 약물의 방출패턴을 조사하였으며 rat을 이용한 in vivo 약동력학 실험을 실시하였다. 또한 이 매트릭스 제형을 같은 세파계 약물인 cephalexin으로의 응용을 시도하였다. 한편 항암제인 5-Fluorouracil을 model 약물로 하여 ethylene-vinylacetate의 microsphere를 제조하여 표면 및 내면의 SEM Characterization 및 in vitro 약물방출실험을 행하였다.인공혈관 개발에 관한 연구에서는 인산화 셀룰로오스의 합성 및 생체적합성을 조사하였으며 인산화 PVA의 합성 및 생체적합성을 조사하였다. 또한 aminated Acrylates의 세포친화성을 조사하여 생체재료로서의 가능성을 평가하였으며 의료용 PVA foam의 개발, PEG-grafted polysaccharide의 합성, 혈관 내피세포 배양등에 관한 연구도 실시하였다.생체조직 심장판막의 개발에 관한 연구에서는 전년도에 확립한 최적의 화학적 개질조건을 대동맥 판막에 적용하여 그 특성을 분석하여 in-vivo 칼슘화 동물실험을 통하여 새로운 조직판막의 조직 및 혈류하에서의 칼슘침착 특성을 평가하였다. 생체적합성이 개선된 인공심장용 재료의 개발에 관한 연구에서는 룸부로키나제 원재료의 대량 분리를 위한 3단계 크로마트그래피법과 HPLC 기법의 조건을 확립하였으며 룸브로키나제의 혈전용해기전을 입증하기 위하여 룸브로키나제 유전자에 대한 클로닝을 수행하였다. 또한 항감염 처리 방법을 개선하여 처리방법이 단순화되고 다양한 균주에 대하여 항균성을 나타내도록 하였다.

Abstract ▼

1. Development of oral drug delivery system 1) Matrix type drug delivery system containing cefadroxil was developed by dispersing drug particles in a hydrophobic polymer using Brabender mixer and press. Various factors affecting the rate of release were investigated. The factors studied were loadi

1. Development of oral drug delivery system 1) Matrix type drug delivery system containing cefadroxil was developed by dispersing drug particles in a hydrophobic polymer using Brabender mixer and press. Various factors affecting the rate of release were investigated. The factors studied were loading amount and the incorporation of additives (algin and Carbopol). It has been shown that, by proper combination of these factors, desired release profile could be obtained. This system is also applied to cephalexin and in vitro characterization was carried out. 2) Pharmacokinetic study of the matrix system containing cefadroxil was carried out, and the data showed that the system is quite promising as a sustained drug delivery carrier. 3) Preparation method for ethylene-vinyl acetate microsphere was established and the release characterized. Marphological study of the surface and the dissected area of the microsphere was also carried out using SEM.2. Development Artificial Vacular Grafts 1) Phosphoryl cellulose was synthesized by a reaction between cellulose and phosphorus pentoxide. According to the results of experiments of platelet adhesion and CHO cell cultures, it was quite blood-andcell-compatible. 2) Phosphoryl PVA was also developed to apply it to the material of small-diameter vascular graftes. It was more blood-compabible, compared to a control, PVA. 3) The cell compatibility of aminated acrylates was studied to test whether it was applicable for small-diameter vascular grafts. Since it was cell-compatible, it might be used for a vascular graft seeded with endothelium.3. Development of artificial tissue valves In order to develop a blood conpatible and thermally stable tissue valve sulfonated polyethylene oxide (PEO-S03) was grafted to poreine valve leaflets, In vivo calcification test of modified poreine tissue valves was studied using dog implantation model. 1) Biologic poreine tissue vlaves were modified by coupling sulfonated polyethylene oxide 2) All chemically modified tissues had significantly higher shrinkage temperatures and collagenase digestion resistance than that of fresh bioprosthetic tissue and bioprostheic tissue valve control. 3) Modified tissue valves had less calcium than didi untreated control during any incubation period. 4) These results of in vitro and in vivo tests suggest that chemically modified tissue vlaves can be commertialize.4. Development of biocompatible materials for artificial heart The final goal of this project is to commercialize the biocompatible to tally implantable artificial heart by developing biocompatible materials which can be applied to other blood-contacting artificial organs. The objectives of the 3rd year was to develop the blood compatible artificial heart and antipinfective marterial using a bacteria sensor system. 1) The three step chromatography and HPLC were established for the mass production of highly purified lumbrokinase. Lumbrokinase-immobilized polyurethane showed no toxicity in the in vivo implantation experiment using a rabbitl. 2) The cloining of lumbrokinase gene was performed to prove the thrombolytic mechanism of lumbrokinase. The amino terminal sequence and genetic library of lumbrokinase were found. 3) Anti-infective treatment method was improved to simplify the method and show better anti-infective action to various bacteria. In the kinetic experiment of bacterial enzyme for optimizing the linkers of antibiotics, PDI and HMDI were proved to be effective linkers of antibiotics. And the immobilized antibiotics were effectively released to blood when bacteria contacted to the surface, which was confirmed from the the experiments of the stability of linkers and the effect of antibiotics in blood.

목차 Contents

• 제 1 장 서론 ... 17
• 제 2 장 과제구성 ... 19
• 제 3 장 세부과제별 연구결과 ... 21
• 제 1 세부과제 : 경구투여용 재료 및 응용개발 ... 21
• 제 2 세부과제 : 인공혈관 개발 ... 31
• 제 3 세부과제 : 생체조직 심장판막의 개발 ... 39
• 제 4 세부과제 : 생체적합성이 개선된 인공심장용 재료의 개발 ... 45
• 제 4 장 결론 ... 53
• 제 5 장 향후 연구계획 ... 55