보고서 정보
주관연구기관 |
안전성평가연구소 Korea Research Institute of Chemical Technology |
보고서유형 | 최종보고서 |
발행국가 | 대한민국 |
언어 |
한국어
|
발행년월 | 2013-02 |
과제시작연도 |
2011 |
주관부처 |
농촌진흥청 Rural Development Administration(RDA) |
과제관리전문기관 |
농촌진흥청 Rural Development Administration |
등록번호 |
TRKO201300014374 |
과제고유번호 |
1395022667 |
사업명 |
차세대바이오그린21 |
DB 구축일자 |
2013-08-26
|
DOI |
https://doi.org/10.23000/TRKO201300014374 |
초록
▼
Ⅲ. 연구개발의 내용 및 범위
○ 천연물 신약(경구, 경피용) 의약부외품 (화장품) 개발 위한 전임상 약리 효능 및 독성 연구 (II)
- 전임상 약리 효능 시험 수행
- 전임상 독성 시험 : 랫드 단회 투여 및 13주 반복투여 독성시험, 피부자극시험, 안점막 자극시험
- 3D 인공피부를 이용한 피부투과력 시험수행
○ 천연물 신약(경구, 경피용) 의약부외품 (화장품) 개발 위한 전임상 약물 동태 연구(II)
○ 천연물 신약(경구, 경피용) 의약부외품 (화장품) 개발 위한 제제연구
○ 시험물질 생
Ⅲ. 연구개발의 내용 및 범위
○ 천연물 신약(경구, 경피용) 의약부외품 (화장품) 개발 위한 전임상 약리 효능 및 독성 연구 (II)
- 전임상 약리 효능 시험 수행
- 전임상 독성 시험 : 랫드 단회 투여 및 13주 반복투여 독성시험, 피부자극시험, 안점막 자극시험
- 3D 인공피부를 이용한 피부투과력 시험수행
○ 천연물 신약(경구, 경피용) 의약부외품 (화장품) 개발 위한 전임상 약물 동태 연구(II)
○ 천연물 신약(경구, 경피용) 의약부외품 (화장품) 개발 위한 제제연구
○ 시험물질 생산 및 공급
Abstract
▼
(1) The pharmacological effect of Platycodon grandiflorum on DNCB –induced atopy-like dermatitis in NC/Nga mice.
Platycodi Radix, the root of Platycodon grandiflorum (PG), is used extensively as an anti-inflammatory agent in the treatment of respiratory ailments such as coughs and colds in Orient
(1) The pharmacological effect of Platycodon grandiflorum on DNCB –induced atopy-like dermatitis in NC/Nga mice.
Platycodi Radix, the root of Platycodon grandiflorum (PG), is used extensively as an anti-inflammatory agent in the treatment of respiratory ailments such as coughs and colds in Oriental areas. Triterpenoid saponins, which are saponin glycosides with an attachment of various sugar molecules to the triterpene unit, have been known to be a major component of Platycodi Radix and can be easily cleaved off in the gut by bacteria. This ability allows them permeate into cell membranes and potentially activate many signaling molecules attached to the membrane.
Some saponins are separated from this root: platycodins (A, D, D2, and D3), polygalacin D2, platyconic acid A, and platycosides (A, B, C, D, E and F). Among them, platycodin D has been known to be effective for the inhibition of COX-2
induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) with suppression of prostaglandin E2 (PGE2) in rat peritoneal macrophages. Another group reported that various platycodin saponins inhibit iNOS and COX-2 gene expression by blocking NF-kappaB activation in LPS-induced RAW 264.7 cells.[12] In addition, Han et al. suggested that saponins derived from roots of PG inhibit anaphylactic reaction and IgE-mediated allergic response in mast cells.[13] Recently, Kim et al. reported that PG inhibits the development of AD-like skin lesions by reducing the Th2 cell response and increasing the Th1 cell on data from serum and isolated splenocytes of atopy-induced NC/Nga mice.
In the present study, we investigated the therapeutic effect of PG extract on AD-like skin lesions induced by 1-chloro-2,4-dinitrobenzene (DNCB) in NC/Nga mice. In addition, immune cell types regulated by PG were characterized using specific inflammatory cell markers.
To develop atopic dermatitis-like lesions, 200 μl of 0.3% 1-chloro-2, 4-dinitro benzene (DNCB) in acetone/olive oil (3:1) was applied 3 times a week for 2 orally administrated at concentrations of 300 and 500 mg/kg every day for 2 weeks. The therapeutic effect of PG on AD-like skin lesions was assessed by measuring skin severity scores and epithermal thickness, serum total immunoglobulin (Ig) E, histopathological findings for inflammatory cells including mast cells, macrophage and T cells, and mRNA expression of various cytokines related to the inflammatory and allergic response. The significance of inter-group differences was analyzed using the ANOVA test. Data were considered to be significant when P < 0.05 or P < 0.01.
Oral treatment of PG suppressed AD-like skin lesions according to the assessment of skin severity and epithermal thickness in the DNCB-treated NC/Nga mice. This alleviation was further correlated with a reduction of elevated serum total IgE or cytokine mRNA in the PG-treated group compared with vehicle-treated positive group. In addition, infiltrated inflammatory cells decreased on the skin lesions compared with vehicle-treated group.
These results suggest that PG may have a potential therapeutic effect for AD via the inhibition of both inflammatory and allergic reaction.
(2) The pharmacokinetic analysis of Platycodon grandiflorum after intravenous and oral administration to S.D rat.
Platycodon grandiflorum (PG) has long been used as a traditional oriental medicine to treat respiratory disorders. Platycodin D (PD) is known as the main component isolated from the roots of PG. A simple and rapid liquid chromatography-tandem mass spectrometry method has been developed and validated for quantitation of PD in rat plasma. In the sample preparation steps,
the protein precipitation with acetonitrile was employed for reducing sample complexity, and notoginsenoside R1 was spiked into the sample as an internal standard. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization and multiple reaction monitoring in the positive ion mode. The total chromatographic run time was 4.0 min, and the calibration curves of PD were linear over the concentration range of 50–10,000 ng/ml in rat plasma. The coefficient of variation and relative error at five QC levels were 1.0 to 8.8% and 0.7 to 8.7%, respectively. After a single oral administration of 500 mg/kg and a single intravenous administration of 25 mg/kg of PD-3% (Platycodon grandiflorum extracts powder including 3% of PD), PD and platycodin D3 (PD3) were detected and their pharmacokinetic parameters were
estimated. The oral bioavailability of PD and PD3 were 0.29% and 1.35% in rats at 500 mg/kg of 3% PD extract of PG, respectively. After a single oral administration of 200 mg/kg and a single intravenous administration of 100mg/kg of PD-1% (Platycodon grandiflorum extracts powder including 1% of PD), PD was detected and their pharmacokinetic parameters were estimated. The oral bioavailability of PD was 0.50~0.54%. The present method can be applied for pharmacokinetic analysis of platycodins and platycosides of PG.
목차 Contents
- 표지 ... 1
- 제출문 ... 2
- 요약문 ... 3
- SUMMARY ... 5
- 목차 ... 8
- 제1장 서론 ... 9
- 제1절 연구개발의 필요성 ... 9
- 제2장 국내외 기술개발 현황 ... 10
- 제1절 국내 연구 현황 ... 10
- 제2절 국외 연구 현황 ... 12
- 제3장 연구개발수행 내용 및 결과 ... 13
- 제1절 천연물 신약 개발시 필요한 전임상 약효 약리 작용 연구 ... 13
- 제2절 천연물 신약 개발시 필요한 전임상 독성시험 자료 확보 ... 23
- 제3절 천연물 신약 개발 시 필요한 3D 인공피부를 이용한 피부투과성 시험자료 확보 ... 27
- 제4절 기능성식품/천연물 신약 개발 위한 전임상 약물동태 연구 ... 28
- 제4장 연구개발목표 달성도 및 대외기여도 ... 50
- 제1절 목표대비 대외 달성도 ... 50
- 제2절 정량적 성과 ... 51
- 제5장 연구개발결과의 활용계획 ... 52
- 제6장 연구개발과정에서 수집한 해외과학기술정보 ... 53
- 제7장 기타 중요 변동사항 ... 55
- 제8장 국가과학기술종합정보시스템에 등록한 연구장비 현황 ... 56
- 제9장 참고문헌 ... 57
- <참고> 주요 연구성과 요약 ... 61
※ AI-Helper는 부적절한 답변을 할 수 있습니다.