초록 ▼

본 과제의 최종목표인 천연물 유래 관절염치료제(NDI10218)의 임상시험계획(IND) 신청을 아래와 같이 비임상 연구를 통해 성공적으로 완료하였음
1) 단회 및 반복 투여와 안전성 약리 시험을 통해 NDI10218의 안전성 확보
2) 류마티성 관절염 및 항진통 동물모델을 이용하여 NDI10218의 유효성 확보
3) 원료 대량 확보, 제조 방법 결정, 원료의약품 생산, 기시법 확보, 제형제제 결정, 완제의약품 생산등의 연구를 통해 NDI10218의 원료 및 완제의약품 규격 확보
4) NDI10218의 임상2상시

본 과제의 최종목표인 천연물 유래 관절염치료제(NDI10218)의 임상시험계획(IND) 신청을 아래와 같이 비임상 연구를 통해 성공적으로 완료하였음
1) 단회 및 반복 투여와 안전성 약리 시험을 통해 NDI10218의 안전성 확보
2) 류마티성 관절염 및 항진통 동물모델을 이용하여 NDI10218의 유효성 확보
3) 원료 대량 확보, 제조 방법 결정, 원료의약품 생산, 기시법 확보, 제형제제 결정, 완제의약품 생산등의 연구를 통해 NDI10218의 원료 및 완제의약품 규격 확보
4) NDI10218의 임상2상시험을 위한 임상시험프로토콜 개발

Abstract ▼

I. Necessity of this study
: Rheumatoid arthritis (RA) is a chronic inflammatory disorder that is characterized by the inflammation and proliferation of synovial joint tissues and often leads to the destruction and deformity of the involed joints. The number of patients with RA is appoximately 1%

I. Necessity of this study
: Rheumatoid arthritis (RA) is a chronic inflammatory disorder that is characterized by the inflammation and proliferation of synovial joint tissues and often leads to the destruction and deformity of the involed joints. The number of patients with RA is appoximately 1% of the world's population (and is increasing every year). The global RA market was approximately $85 billion in 2009 and is expected to grow to $120 billion in 2016. RA drugs include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease modifying anti-rheumatic drugs (DMARDs) and biological agents. There is no cure for RA,and current medications are focused on alleviating symptoms and/or preventing further destructions. RA drugs often have severe side effects upon long-term use. Development of TA drugs with higher efficacy and safety is urgently needed.
II. Final goal of this study
: Submitting the investigational new drug application (IND) to KFDA for botanical drug NDI10218 for rheumatoid arthritis
III. Contents and province of this study
1. Preclinical pharmacology and toxicology
: single and repeated dose toxicity, safety pharmaclology, homogeneity and stability of botanical drug substance
2. Animal efficacy and mechanism
: Collagen-induced arthritis (CIA) animal model, Acetic acid-induced writhing animal model
3. Chemistry, manufacturing, and controls
1) (Botanical) drug substance: Supply of raw material, manufacturing process, process controls, and process validation
2) (Botanical) drug product: formulation, production, stability
4. Development of IND application protocol
5. Submission of IND application
IV. Results of this study
1. Safety data
1) Single or repeat dose toxicity test (rodents)
(1) Single dose: approximate lethal dose (ALD) is 5,000 mg/kg or more
(2) Repeat dose: no toxic symptoms up to 2,000 mg/kg
2) Single or repeat dose toxcity test (non-rodents)
(1) Single dose: minimal lethal dose (MLD) is 2,000 mg/kg or more
(2) Repeat dose: no toxic symptoms up to 600 mg/kg
3) Safety Phamacology
(1) Cardiovascular system: no toxic symptoms up to 1,000 mg/kg
(2) Central nervous system: no toxic symptoms up to 1,000 mg/kg
(3) Respiratory system: no toxic symptoms up to 1,000 mg/kg
4) Homogeneity and stability of botanical drug substance
: NDI10218 drug substance is homogeneous and stable for safety test
2. Efficacy data
1) Collagen-induced arthritis (CIA) mice model
: NDI10218 showed anti-arthritic effects in a dose-dependent manner.
2) Acetic acid-induced writhing animal model
: Analgesic effect of NDI10218 was confirmed at 100 mpk.
3. Chemistry, manufacturing, and controls drug substance: Supply of raw material, process controls, process validation
1) Drug substance
(1) Supply of raw material:One ton of raw material was obtained.
(2) Manufacturing process: 50% ethanol extraction
(3) Production of drug substance: 500g of drug substance from 1kg of raw material
(4) Stability of drug substance: stable
(5) Process controls and process validation: Chebulagic acid was identified as an active ingredient and chosen to be a characteristic marker.
2) Drug product:
(1) Formulation: tablet
(2) Production: 예: tablets of 100mg of NDI10218, tablets of placebo
(3) Stability: Drug product was stable
4. Development of IND application protocol
: A multicenter, randomized, and double-blind protocol for phase II clinical trial was prepared
5. Submission of IND application
: IND application was filed on Nov.23, 2010
V. Plans for the application of research results
1. Phase II and phase III clinical trials for rheumatoid arthritis
2. Application of NDI10218 for other inflammatory diseases such as asthma, atopic dermatitis and psoriasis
3. Technology Transfer for further development

목차 Contents

• 표지 ...1
• 목차 ...2
• I. 총괄현황 ...3
• 1. 겉표지(앞면) ...4
• 2. 제출문 ...5
• 3. 보고서 요약서 ...6
• 4. 요약문(한글) ...7
• 5. 요약문(영문) ...9
• 6. 연구 성과 실적 및 향후 계획 ...11
• 7. 참여연구원 현황표 ...17
• II. 총괄연구과제 연구결과 ...18
• 1. 연구개발과제의 배경 및 필요성 ...19
• 2. 국내외 기술개발 현황 ...32
• 3. 연구개발과제의 추진체계 ...38
• 4. 연구개발 수행 내용 및 결과 ...40
• 5. 목표달성도 및 관련분야 기여도 ...93
• 6. 향후 연구성과 추진 계획 ...94
• 7. 연구개발결과의 파급효과 ...95
• 8. 연구개발결과의 활용계획 ...96
• 9. 연구개발과정에서 수집한 해외과학기술정보 ...98
• 10. 참고문헌 ...99
• III. 첨부서류 ...100
• 목차 ...101
• 1. 자체평가의견서 ...102
• 2. 실적 증빙자료 ...106
• 3. 기타 첨부서류 ...119