초록 ▼

주사제로 제공되는 옥살리플라틴 (Eloxatin)은 독성 및 투약에 따른 환자 순응도 저하, 처치에 소요되는 약제비등의 문제점을 해결할 수 있는 경구제 개발이 시급함. 본 연구는 해외 IND 신청을 위한 비임상 자료확보를 위하여 해외 IND 승인 경험이 풍부한 국내외 전문 CRO를 통하여 경구용 나노옥살리플라틴 제제화 가능성을 확인하는 비임상 시험을 실시 하였음. 투여경로 변경을 위한 항암제옥살리플라틴의 경구 제제화를 위하여 나노입자화를 통한 생체이용률의 개선과 독성을 경감시키고 항암활성을 극대화하여 경구제제화 가능성을 확인하였음.

주사제로 제공되는 옥살리플라틴 (Eloxatin)은 독성 및 투약에 따른 환자 순응도 저하, 처치에 소요되는 약제비등의 문제점을 해결할 수 있는 경구제 개발이 시급함. 본 연구는 해외 IND 신청을 위한 비임상 자료확보를 위하여 해외 IND 승인 경험이 풍부한 국내외 전문 CRO를 통하여 경구용 나노옥살리플라틴 제제화 가능성을 확인하는 비임상 시험을 실시 하였음. 투여경로 변경을 위한 항암제옥살리플라틴의 경구 제제화를 위하여 나노입자화를 통한 생체이용률의 개선과 독성을 경감시키고 항암활성을 극대화하여 경구제제화 가능성을 확인하였음. 또한 본 연구를 통해 확립된 나노 입자 제조 기술은 향후 난용성 약물의 가용화 및 생체이용률 개선을 목적으로하는 제품화 연구에 범용적으로 활용 가능하며, 기존 초임계유체 제조 기술의 적용 약물 제한성을 크게 개선시켜 관련기술의 경쟁력 우위의 독보적 기술을 확립하였음.

Abstract ▼

Oxaliplatin is the first platinum-based anticancer drug approved for the treatment of colorectal cancer. It is typically administered intravenously due to low oral bioavailability. In this study, we developed an oral DDS of oxaliplatin utilizing our proprietary nanotechnology, the Fat Employing Supe

Oxaliplatin is the first platinum-based anticancer drug approved for the treatment of colorectal cancer. It is typically administered intravenously due to low oral bioavailability. In this study, we developed an oral DDS of oxaliplatin utilizing our proprietary nanotechnology, the Fat Employing Supercritical Nano System (FESNS) and confirmed the possibility of oral formulation through preclinical studies. Now, we intend to develop the competitive oral DDS & oral anti-cancer drug through achieving non-clinical studies of global levels that meet FDA/EMEA IND and clinical
studies requirements.
I. Objects of R&D
We intend to establish the manufacturing technology and evaluate the in vitro & in vivo properties of nano-oxaliplatin using supercritical fluids and improve the oral bioavailability/ toxicity profile of oxaliplatin nanoparticles. The aims of this study are development of a globally competitive DDS for orally administrative formulation of oxaliplatin through preclinical/clinical studies and the out-licensing of FESNS technology.
II. Description and range of the R&D
Oxaliplatin when applied through infusional chemotherapy for colon cancer has disadvantages of increased inconvenience, side effects, and costs. In order to overcome these disadvantages of oxaliplatin, we established a large scale manufacturing process and develop the oral DDS technology to achieve the similar efficacy or superior to the intravenous formulation. We also optimized and evaluated oral formulation of oxaliplatin nanoparticles with in vitro/ in vivo preclinical studies, and confirmed the stability of the formulation. This technology's intellectual property rights are protected by Korea and PCT patent application. Additional non-preclinical studies for clinical study, CMC documentation for IND application, stability test of final formula, preparation of clinical samples are in-progress.
III. Results of R&D
We completed the establishment of manufacturing process of oxaliplatin nano particulation and confirmed the possibility of mass production. FESNS provided reproducible nano oxaliplatin with high manufacturing yield (> 95%), and the particle size, which is one of the most important parameter in evaluation of nanoparticle manufacturing was below 300 nm and showed an even distribution. We conducted in vitro & in vivo general toxicity studies, genotoxicity studies, safety pharmacologies and general pharmacologies for nano oxaliplatin to obtain data for global IND application. The data showed that oral nano-oxaliplatin is superior in toxicity and efficacy at the pharmacologically active doses compared to Eloxatin in in vitro and in vivo tests with rats. In addition, we improved existing technology which are limited to be only applicable to lipid soluble API. We achieved to widen the range of API to water soluble drug. The results above were filed on Korea patent application.
IV. Plans for R&D results
Technology developed by this project will apply to various intravenous anti-cancer drugs for oral formulation. And through the improvement of solubility and saving costs through process enhancement, we will expand global competitivity using this technolgy. Then, oral anti-cancer drug products using this technology will be applied IND based on the performed non-cilnical studies. Especially, we will perform the global clinical studies through out-licensing and co-development with global pharmaceutical company.

목차 Contents

• 표지...2
• 제출문...4
• 보고서 요약서...5
• 요약문...6
• SUMMARY...8
• 연구 성과 실적 및 향후 계획...10
• 참여연구원 현황표...18
• II. 총괄연구과제 연구결과...19
• 1. 연구개발과제의 배경 및 필요성...20
• 2. 국내외 기술개발 현황...22
• 3. 연구개발과제의 추진체계...29
• 4. 연구개발수행 내용 및 결과...31
• 5. 목표달성도 및 관련분야 기여도...53
• 6. 향후 연구성과 추진 계획...54
• 7. 연구개발결과의 파급효과...54
• 8. 연구개발결과의 활용계획...56
• 9. 연구개발과정에서 수집한 해외과학기술정보...58
• 10. 참고문헌...59
• III. 첨부서류...60