초록 ▼

Ⅱ. 연구 결과: 한약재 구성 성분, 단일 한약재, 한약 처방 등과 케미칼 약물의 병용 투여시 한약 유래 성분과 케미칼 약물 간의 pharmacokinetics와 CYP450 효소대사에 상호 영향을 미치는 것으로 나타남. 기관지세포를 이용한 실험에서는 한약처방 (KE-11, -13, -16)과 케미칼 약물 (Montelukast)의 복합 투여시, 단독 처리 했을 때와 비교할 때, 억제 효과에 대한 상승효과 (synergic effect)가 나타나는 것을 확인하였음.
NCI-H292 세포를 이용한 항천식 효능에서는 KE-20과

Ⅱ. 연구 결과: 한약재 구성 성분, 단일 한약재, 한약 처방 등과 케미칼 약물의 병용 투여시 한약 유래 성분과 케미칼 약물 간의 pharmacokinetics와 CYP450 효소대사에 상호 영향을 미치는 것으로 나타남. 기관지세포를 이용한 실험에서는 한약처방 (KE-11, -13, -16)과 케미칼 약물 (Montelukast)의 복합 투여시, 단독 처리 했을 때와 비교할 때, 억제 효과에 대한 상승효과 (synergic effect)가 나타나는 것을 확인하였음.
NCI-H292 세포를 이용한 항천식 효능에서는 KE-20과 montelukast 복합투여 시, 단독 처리에 비해 MUC5AC 생성과 유전자 발현량이 더 억제되었으며, 동물실험에서도 이와 유사한 효과를 확인하였음. 따라서 한약 처방과 케미칼 약물의 복합 투여 시, 항천식에 대한 시너지 효과가 있을 것으로 판단됨

Abstract ▼

Ⅱ. Objective and Necessity
The previous studies demonstrated that the components from herbal medicine or herbal formula influenced pharmacokinetics or CYP450 enzyme activity of chemical anti-asthma drug, showing the decrease or increase of bioavailability of chemical drugs.
KE-02, 11, 13, 16 a

Ⅱ. Objective and Necessity
The previous studies demonstrated that the components from herbal medicine or herbal formula influenced pharmacokinetics or CYP450 enzyme activity of chemical anti-asthma drug, showing the decrease or increase of bioavailability of chemical drugs.
KE-02, 11, 13, 16 and 20 is used as a traditional herbal medicine in Korea and other Asian countries to treat various diseases. Montelukast has been used as therapeutic agent for prevention and treatment of allergic rhinitis or asthma. In the present study, we investigated the synergy effect on interaction of each KE-02, 11, 13, 16 (in vitro), 20 (in vivo) and montelukast using human bronchial epithelial, BEAS-2B cells, and BALB/c mice. Anti-asthma and anti-inflammation activities were selected to study the effects on IL-4/TNF-α-induced inflammatory response in vitro cell culture model using BEAS-2B cells and OVA-induced asthmatic response in vivo mouse model.
In vitro; supernatants were collected and the cellular responses, including biological indicator determined via enzyme-linked immunosorbent assay and zymography. IL-4 and TNF-αwere significantly induced the production of eotaxin-3, eotaxin, regulated on activation of normal T-cell-expressed-and-secreted (RANTES) and matrix metalloproteinases-9 (MMP-9) activity in BEAS-2B cells. KE-02, 11, 13, 16 and montelukast significantly inhibited the production of biological indicator. Moreover, drug combinations (co-treatment of each KE-02, 11, 13, 16 with montelukast) were more effective than single treatment, although difference of treatment time was not significant.
Herbal remedy has been clinically used in combination with commercial drugs for maximizing its curative effects. KE-20, an important multi-herb remedy in Asia, has been known as a useful prescription for treating various inflammatory and immune diseases. Montelukast is an anti-asthmatic drug and acts a leukotriene D4 receptor antagonist. In this study, we investigated the effects of KE-20, montelukast, and in combination on MUC5AC production in NCI-H292 cells. KE-20 treatment significantly reduced the MUC5AC production on concentration dependent manner in epidermal growth factor (EGF)-stimulated NCI-H292 cells. However, montelukast treatment did not exhibit a significant reduction in MUC5AC production in EGF-stimulated NCI-H292. However, combination of KE-20 and montelukast significantly reduced the MUC5AC production, which more effective than those of KE-20 alone. These results were consistent with the expression of MUC5AC mRNA. KE-20 treatment decreased the MUC5AC mRNA expression in EGF-stimulated NCI-H292. Combination of KE-20 and montelukast markedly reduced the MUC5AC mRNA expression, which more decreased than that of KE-20 alone. These results indicate that KE-20, montelukast, and in combination attenuated the MUC5AC production in EGF-stimulated NCI-H292 cells. Combination of KE-20 and montelukast is more effective to inhibit MUC5AC production than those of KE-20 or montelukast alone. Therefore, our results suggest that KE-20 combined with montelukast may be more effective than commercially established therapeutic for asthma or chronic obstructive pulmonary disease related with excess mucin production.
CYP450, the most important drug-metabolizing enzyme system, is play a key role in metabolism of various xenobiotics, including herbal medicines and chemicals.
Among them, CYP3A4 is responsible for the metabolism of montelukast. In this study, we performed reverse transcriptase PCR to determine the influences of KE-20 and montelukast on the mRNA expression of CYP3A4 in NCI-H292 cells. The mRNA expression of CYP3A4 was decreased by KE-20 and montelukast compared with EGF. In addition, co-treatment of KE-20 and montelukast decreased the expression of CYP3A4 more than each treatment of KE-20 and montelukast. These results suggested that the co-administration of KE-20 and montelukast are likely to cause clinically adverse effects.
In vivo; BALB/c mice were sensitized by an intraperitoneal injection of OVA and subsequently challenged with nebulized OVA. We investigated the number of inflammatory cells, the production of Th2 cytokines and chemokine in bronchoalveolar lavage fluid (BALF), histological changes in lung tissue. KE-20 (300 mg/kg) decreased the accumulation of inflammatory cells, production of Th2 cytokines and chemokine in BALF. Moreover, drug combinations (co-treatment of KE-20 300 mg/kg with montelukast) were more effective than single treatment.
These results suggest that each KE-02, 11, 13, 16 and 20 combined with montelukast may be useful to ameliorate airway inflammation response In vitro and In vivo. These data indicates that a potential for herb-drug interactions to be supplements when each KE-02, 11, 13, 16 and 20 is consumed with montelukast.

목차 Contents

• 표 지 ... 1
• 제 출 문 ... 2
• 보고서 초록 ... 4
• 요 약 문 ... 6
• SUMMARY ... 10
• Contents ... 12
• - 목 차 - ... 13
• - 표목차 - ... 15
• - 그림목차 - ... 16
• 제 1 장 구개발의 목적 및 필요성 ... 18
• I. 연구개발의 목적 ... 18
• Ⅱ. 연구개발의 필요성 ... 18
• 1. 추진 배경 및 과학기술적 의의 ... 18
• 2. 국내외 연구동향 ... 21
• 3. 사업추진의 타당성 ... 23
• 4. 연구개발 추진 전략 ... 26
• 5. 기대효과 ... 27
• 제 2 장 연구개발의 내용 및 범위 ... 28
• I. 한·양약 복합 투여 현황 분석 ... 28
• 1. 국내·외 논문 및 보고서 분석 ... 28
• Ⅱ. 천식치료에 대한 한·양약 복합 투여 효능 검증 ... 29
• 1. In vitro 유효성 검증 ... 29
• 2. In vivo 유효성 검증 ... 31
• 제 3 장 연구개발 결과 ... 34
• I. 한·양약 복합 투여 현황 분석 ... 34
• 1. 국내·외 논문 및 보고서 분석 ... 34
• Ⅱ. 천식치료에 대한 한·양약 복합 투여 효능 검증 ... 45
• 1. In vitro 유효성 검증 ... 45
• 2. In vivo 유효성 검증 ... 70
• 제 4장 연구결과의 활용계획 ... 74
• I. 과학기술적 성과 ... 74
• Ⅱ. 성과활용ㆍ확산계획 및 실적 ... 74
• 참 고 문 헌 ... 78
• 끝페이지 ... 84