표제지
목차
약어 12
국문초록 13
I. 서론 15
1. 연구배경 15
2. 이론적 배경 18
2.1. 실리콘오일의 체내 동태 및 안전성 18
2.2. 국·내외 관련 규정 20
2.3. 기존 분석방법 23
2.4. 실리콘오일 라만밴드 26
2.5. 라이브러리 매칭률 개선을 위한 통계적 방법 27
2.6. 모델링 방법 28
3. 연구목적 및 범위 30
II. 실험방법 32
1. 시료 및 전처리 32
2. 분석기기 및 소프트웨어 34
3. 스펙트럼 전처리 및 모델링 35
IV. 결과 및 고찰 36
1. 표준품 라만스펙트럼 수집 36
2. 시판품 중 실리콘오일 분석 40
2.1. 실리콘오일의 분석 40
2.2. 유출된 실리콘오일 입자 크기 검토 48
2.3. 주성분과 실리콘오일의 상호작용 가능성 검토 53
3. 실린지 기벽 측정 66
3.1. 실린지 기벽 내 실리콘오일 분포 확인 66
3.2. 실린지 스펙트럼에서 실리콘오일 피크 추출 71
4. 라이브러리 매칭률 개선 73
V. 결론 및 제언 79
참고문헌 81
ABSTRACT 88
Table 1. Regulations on the management of leached silicone oil particles from pharmaceutical containers in major countries 22
Table 2. Characteristic Raman bands of Silicone oil 26
Table 3. Analytical method applied to front opened filtrated debris for commercial product 45
Table 4. Analysis method applied to back opened filtrated debris for commercial product 45
Table 5. Size measurement and distribution of silicone oil particles leached from the container 49
Table 6. Analytical conditions and HQI analysis results for each type of silicone oil leached from the container 52
Figure 1. Schematic diagram of research background and management method for detecting leached silicone oil... 17
Figure 2. a) A picture of the commercial drug used in this study (source: Daehan Pharmaceutical Industry homepage), b)... 33
Figure 3. Raman spectrum of standard polydimethylsiloxane (PDMS) 36
Figure 4. Raman spectrum of sodium chloride powder 38
Figure 5. Raman spectrum of silicone oil and sodium chloride powder mixture 39
Figure 6. Microscopic images of silicone oil from the commercial product on the filter 40
Figure 7. Raman spectrum of the leached silicone oil from the commercial product 41
Figure 8-1. Raman spectra according to variation of excitation power under setting analytical conditions for silicone... 43
Figure 8-2. Raman spectra according to variation of excitation power under setting analytical condition for silicone... 44
Figure 9. Peak assign for the leached silicone oil in Raman spectrum of commercial isotonic sodium chloride... 47
Figure 10. Size distribution of silicone oil particles leached from the container 50
Figure 11. Raman spectrum of the silicone oil with calcium salt in the commercial product 53
Figure 12. a) Microscopic image and b) Raman spectrum of the NaCl powder with the calcium salt 55
Figure 13-1. The result of XY mapping analysis showing the highest intensity of filter peak in the measurement of sample mixed... 57
Figure 13-2. The result of XY mapping analysis showing the highest intensity of calcium salt peak in the measurement of sample... 58
Figure 13-3. The result of XY mapping analysis showing the highest intensity of silicone oil peak(2906 cm-1) in the...[이미지참조] 59
Figure 13-4. The result of XY mapping analysis showing the highest intensity of silicone oil peak(2966 cm-1) in the...[이미지참조] 60
Figure 14. Results of XZ mapping analysis of commercially available product filtered debris analyzed from white... 62
Figure 15-1. As a result of measuring the filtered debris of commercial product by XYZ mapping and analyzing... 64
Figure 15-2. As a result of measuring the filtered debris of commercial product by XYZ mapping and analyzing... 65
Figure 16. Microscopic images of the inside wall of the syringe barrel. a) plastic and b) silicone oil 66
Figure 17. Raman spectrum of the plastic from the inside wall of the syringe barrel 67
Figure 18. Raman spectrum of the silicone oil from the inside wall of the syringe barrel 67
Figure 19-1. The mapping analysis result of the same site measurement cross-section inside the barrel of the... 69
Figure 19-2. The mapping analysis result of the same site measurement cross-section inside the barrel of the... 70
Figure 20. Microscopic image and XY mapping analysis result of the cross-section measurement site inside the... 71
Figure 21. Raw spectrum and subtracted silicone oil spectrum from XY mapping analysis for cross-section inside of... 72
Figure 22-1. The partial least squares regression (PLSR) - leverage correction (LC) model for hit quality... 74
Figure 22-2. The partial least squares regression (PLSR) - cross Validation (CV) model for hit quality... 75
Figure 23. Box and whisker plot of the predicted hit quality indexes for the PLSR-LC model. MSC : multiplicative... 77