초록 ▼

본과제의 합성 및 제조 공정 연구를 통해 보다 생산성이 높은 합성 공정이 가능해졌으며 전임상 실험 및 제제 연구를 위한 DA-8031의 대량 합성과 임상 1상을 위한 DA-8031의 대량 합성에 성공하였음. 원료분석을 통해 물질에 대한 기본 정보를 확보하였고 원료의 기시법을 확정하고 분석법 밸리데이션을 실시하여 물질에 대한 검사법을 구축하고 원료의 안정성을 지속적으로 확보하여 향후 상업화에 대비하고 있음.
제제연구는 제제처방, 제제 방법, 제제용 용기, 포장, 제조 공정, 제제 기준 및 시험법 등을 확립하였음. 또한 시험 생산

본과제의 합성 및 제조 공정 연구를 통해 보다 생산성이 높은 합성 공정이 가능해졌으며 전임상 실험 및 제제 연구를 위한 DA-8031의 대량 합성과 임상 1상을 위한 DA-8031의 대량 합성에 성공하였음. 원료분석을 통해 물질에 대한 기본 정보를 확보하였고 원료의 기시법을 확정하고 분석법 밸리데이션을 실시하여 물질에 대한 검사법을 구축하고 원료의 안정성을 지속적으로 확보하여 향후 상업화에 대비하고 있음.
제제연구는 제제처방, 제제 방법, 제제용 용기, 포장, 제조 공정, 제제 기준 및 시험법 등을 확립하였음. 또한 시험 생산된 제제를 이용하여 제제 안정성을 확인하였음. 약리 연구는 in vitro를 통한 물질의 스크리닝, ex vivo 및 in vivo를 통한 효력 평가 그리고 sexual behavior 관찰 실험을 통하여 DA-8031의 효력을 평가하였음. 그 결과 DA-8031은 세로토닌 수송체에 매우 특이적이고 동물 모델에서 사정의 지연 및 저해를 야기하는 것을 확인함. 독성연구는 KFDA 가이드라인에 따라 수행되어 DA-8031의 안전성에 대해 확립하였음.
이러한 데이터를 바탕으로 식약청으로 부터 임상1상에 대한 IND 승인서를 득하여 현재 임상 1상 준비중에 있음.

Abstract ▼

Premature ejaculation (PE) is one of typical men's health problems, although there is not a common definition for symptom. However, it is normally accepted that premature ejaculation has common characters like following. ① latency time is very short from insert to ejaculation ② People has difficulti

Premature ejaculation (PE) is one of typical men's health problems, although there is not a common definition for symptom. However, it is normally accepted that premature ejaculation has common characters like following. ① latency time is very short from insert to ejaculation ② People has difficulties for controlling ejaculation ③ Male and his partner has stress for this symptom.
It is reported that 60-70% of male population suffers from premature ejaculation, which is 2.5~4 times higher than erectile dysfunction. In USA, it is supposed that 50 million men suffered from this disease. Until now, as PE is recognized as one of "Quality of Life" related disease, the future medication for PE is quite important for improving men's "Quality of Life".
In this grant, Dong-A pharmaceutical performed research as following.
1. Organic synthesis and optimizing manufacturing process for DA-8031
2. Analysis of material and material stability for DA-8031
3. Pharmaceutical research for DA-8031
4. Pharmacological research for DA-8031
5. Toxicological research for DA-8031
6. Absorption/Distribution/Metabolism/Excretion research for DA-8031
Through organic synthesis and optimizing manufacturing process, Dong-A pharmaceutical established more economic & optimized manufacturing process to produce DA-8031 for preclinical study, pharmaceutical research and phaseI clinical trial. For further pharmacological characterization of DA-8031, isoforms of DA-8031 (S-DA-8031, R-DA-8031) were isolated successfully.
Analysis of material stability is essential research for obtaining fundamental information for DA-8031. Through establishment of protocol for validation and analysis, Dong-A pharmaceutical prepared commercialization of DA-8031. Pharmaceutical research included formulation, method, container, package, pharmaceutical manufacturing process and establishment of DA-8031 standard. Based on the established data, Dong-A pharmaceutical produced DA-8031 tablets for clinical phase I trial. And also, DA-8031 tablets for clinical phase I trial was analysed for pharmaceutical stability. Pharmacological research proved the efficacies of DA-8031 in vitro, ex vivo and in vivo. In vitro pharmacological profiling revealed that DA-8031 binds to serotonin transporter selectively. Paralleled to in vitro study, in vivo data demonstrated the efficacy of DA-8031 to inhibit and delay ejaculation in animal models. In case of sexual behavior animal model, DA-8031 delayed the IELT (Intravaginal Ejaculatory Latency Time). Data from toxicological research is essential for new drug developments. For IND application in South Korea, Dong-A pharmaceutical performed toxicological study based on KFDA guideline. As results, data demonstrated that DA-8031 has similar toxicological profiles compared to SSRIs.
DA-8031 has been developed for oral premature ejaculation therapy. While Priligy, world first oral premature ejaculation therapy, did not be approved by FDA, Priligy was approved by EMEA and KFDA, which is on sale in several european countries and South Korea. Nowadays, world wide market share for oral premature ejaculation therapy is supposed to 50 billion dollars. Successful development of DA-8031 can share the world market because there are few candidates for PE treatment pipeline.
Based on the data from this grant, Dong-A pharmaceutical has plan to perform phase I clinical trial in 2010 in South Korea and finally in 2014, DA-8031 will be launched in Korean market. Dong-A pharmaceutical also has portfolio for erectile dysfunction therapy, Zydena. There are a few reports that medicines for erectile dysfunction are effective to cure PE. Based on these reports and data from this grant, Dong-A pharmaceutical can develop the combination therapy for ED and PE.

목차 Contents

• 표지 ... 1
• 제출문 ... 3
• 보고서 요약서 ... 4
• 요 약 문 ... 5
• SUMMARY ... 7
• 연구 성과 실적 및 향후 계획 ... 9
• 참여연구원 현황표 ... 13
• II. 총괄연구과제 연구결과 ... 15
• 1. 연구개발과제의 배경 및 필요성 ... 16
• 2. 국내외 기술개발 현황 ... 20
• 3. 연구개발의 추진체계 ... 24
• 4. 연구개발수행 내용 및 결과 ... 26
• 5. 목표달성도 및 관련분야 기여도 ... 39
• 6. 향후 연구성과 추진 계획 ... 40
• 7. 연구개발결과의 파급효과 ... 40
• 8. 연구개발결과의 활용계획 ... 41
• 9. 연구개발과정에서 수집한 해외과학기술정보 ... 44
• 10. 참고문헌 ... 45
• IV. 첨 부 서 류 ... 49
• 끝페이지 ... 51