보고서 정보
주관연구기관 |
한국한의학연구원 Korea Institute of Oriental Medicine |
연구책임자 |
하혜경
|
참여연구자 |
신현규
,
서창섭
,
이미영
,
진성은
,
전우영
,
유새롬
,
이나리
,
장지혜
,
박은숙
,
최수산나
,
오달석
,
이승훈
,
오성만
,
이채림
,
박태용
|
보고서유형 | 최종보고서 |
발행국가 | 대한민국 |
언어 |
한국어
|
발행년월 | 2018-02 |
과제시작연도 |
2017 |
주관부처 |
과학기술정보통신부 Ministry of Science and ICT |
등록번호 |
TRKO201800022951 |
과제고유번호 |
1711063928 |
사업명 |
한국한의학연구원연구운영비지원 |
DB 구축일자 |
2018-06-30
|
키워드 |
한방 처방.안전성.유효성.한·양약 상호작용.정보구축.병용 근거.과민성대장증후군.삼령백출산.Herbal formula.safety.efficacy.herb-drug interaction.database construction.concomitance evidence.irritable bowel syndrome.Samryungbaekchul-san.randomized controlled trial.
|
DOI |
https://doi.org/10.23000/TRKO201800022951 |
초록
▼
• 한약 처방 25종을 대상으로
- 25종 한약 처방의 추출물 제조, HPLC를 이용한 25종 처방의 다성분 동시분석법 설정 및 함량분석
- 5종 처방에 대한 유전독성 (복귀돌연변이, 소핵, 염색체이상 시험), 25종 처방의 단회 투여 독성 및 5종 처방의 반복 투여 독성에 대한 안전성 연구
- 25종 처방에 대한 면역계 질환 (염증, 아토피, 천식), 순환기계질환 (고혈압), 소화기계질환 (위염, 간손상), 대사성관련 질환 (비만), 비뇨생식기계 질환 (신손상) 등의 유효성 및 기전 연구
- 3종 처방의 탕전
• 한약 처방 25종을 대상으로
- 25종 한약 처방의 추출물 제조, HPLC를 이용한 25종 처방의 다성분 동시분석법 설정 및 함량분석
- 5종 처방에 대한 유전독성 (복귀돌연변이, 소핵, 염색체이상 시험), 25종 처방의 단회 투여 독성 및 5종 처방의 반복 투여 독성에 대한 안전성 연구
- 25종 처방에 대한 면역계 질환 (염증, 아토피, 천식), 순환기계질환 (고혈압), 소화기계질환 (위염, 간손상), 대사성관련 질환 (비만), 비뇨생식기계 질환 (신손상) 등의 유효성 및 기전 연구
- 3종 처방의 탕전법 연구 및 5종 처방의 전탕팩 유통기간 설정 연구
- 25종 처방의 약물대사효소 활성 평가, 한·양약 병용 유효성 상호작용 및 병용 시 약물대사의 약동학적 변화 평가
- 25종 처방 한의 고문헌 분석, 한약처방 의약품 정보 작성 및 52종 처방 정보 업데이트
• 한약제제와 의약품의 병용투여 연구에서는
- 부형제 제외된 한약제제 공급 (쯔므라 6종, 크라시에 7종을 추가 확보)
- 수술 후 침치료의 통증경감에 대한 혜택을 잔뇨감, 추운기분, 위장관 불편감을 해소하는데 기여할 수 있음
- HepaRG 세포주에서 글루타치온 분비를 늘려 간손상을 경감시키는 기전을 밝힘
- 관절염증과 관련된 TNF-a, MAPK, MMP기전 탐색함. 정제부자와 메토트렉세이트의 상승효과 확인
- 한방병원 입원환자의 간손상을 관찰하여 의약품과 한약의 부작용 프로파일 관찰 (간손상 빈도 0.6%)
• 한·양약 병용 임상 유효성, 안전성 연구에서는
— “과민성장증후군(설사형) 환자에 대해 삼령백출산과 Octylonium Bromide 병용투여 유효성 및 안전성 임상연구” 를 위한 임상연구 프로토콜 개발, CRF 개발, CRIS 임상연구 등록, 임상연구 IRB 승인, 식약처 임상연구 계획 승인을 거쳐 현재 임상연구 80 증례 모집 종료
- 임상 데이터에 대한 전문 업체의 DM (Data Manangement) 이후 연구결과 분석 진행
( 출처 : 보고서 초록 5p )
Abstract
▼
Traditional medicines have a very long history. It is the sum total of the practices based on the theories, beliefs and experiences. Medicinal herbs and herbal formulas are generally considered as safe a more than medication. The increasing use of herbal medicines, as a complementary and alternative
Traditional medicines have a very long history. It is the sum total of the practices based on the theories, beliefs and experiences. Medicinal herbs and herbal formulas are generally considered as safe a more than medication. The increasing use of herbal medicines, as a complementary and alternative medicine, is due to a variety factors, including limitations of current therapy and adverse effects of conventional drugs. Although there are many traditional herbal medicines avaliable, and some have been verified by clinical trials, their efficacy and safety are still questioned by consumers.
The present study conducted research to prove the safety and efficacy of herbal formulas taken by the general public, and established and provided a reservoir of comprehensive scientific information on herbal formulas.
Part I. Construction of scientific evidences for herbal medicine formulas
1. Simultaneous determination of the major components in herbal formulas
The standardization of herbal formula for experimental research and clinical therapy still remains to be settled; hence appropriate methods for quality control are needed. In the present study, the simultaneous analysis methods of multiple components have been developed for the index ingredients of medicinal herbs constituting 27 herbal formulas using the HPLC—PDA system.
2. Safety evaluation of 25 herbal formulas
As a part of safety evaluation of herbal formula, acute and sub-chronic oral dose toxicity studies were conducted to investigate the potential toxicity after single or 13-week repeated oral dose administration of herbal formula in rats. The studies were carried out in compliance with the Good Laboratory Practice (GLP) and the Test Guidelines of OECD and the Ministry of Food and Drug Safety (MFDS). To assess the genotoxicity of herbal formulas, a bacterial mutagenicity test (Ames), a chromatin aberration test and an in vivo micronucleus (MN) test were conducted. The aim of a genotoxic assay is to detect carcinogens and other mutagens. The genotoxicity study was carried out in compliance with the Test Guidelines of the Organization for Economic Cooperation and Development (OECD). The summary of results is as follows.
3. Efficacy evaluation of 25 herbal formulas
In the present study, we evaluated the anti-inflammatory and anti-allergic effects of herbal formulas by measuring its inhibition of the production of inflammatory medicators and cytokines in lipopolysaccharide (LPS)-treated RAW264.7 cells, phorbol—12 myristate 13-acetate (PMA)/A23187 — stimulated histamine production in MC/9 cells, thymus and activation-regulated chemokine (TARC/CCL17) expression in TNF—a /IFN-γ-treated HaCaT cells, and the atopic dermatitis response in NC/Nga mice. BEAS — 2B bronchial epithelial cells and ovalbumin-induced asthma mouse model were used as the allergic asthma models. To evaluate of efficacy for lipid metabolism, the herbal formulas were applied on adipogenesis assay in 3T3—L1 adipocytes and high fat diet-induced obese mouse model. In addition, in vitro and in vivo models of various diseases were used to assess the efficacy of herbal formulas. The summary of results is as follows.
On the other hand, due to the increasing use of herbal formulas and herbal dietary supplements, consumers need to whether adverse effects might arise from using these natural products in combination with conventional drugs. The evidence of interactions between herbal formulas and conventional drugs is based on recognized pharmacologic efficacies or safeties commonly lack related information. We investigated the activities of drug metabolizing enzymes (CYP450s and UGTs) and herb-drug interaction on combination of herbal formula with conventional drug, for example acetaminophen. The summary of results is as follows.
4. Establishment of scientific information for herbal formulas
The safety and therapeutic efficacy of herbal formulas must be evaluated via clinical trials and basic scientific research to establish the foundation of evidence based medicine (EBM). We searched several databases including National Discovery for Science Leaders, Oriental Medicine Advanced Searching Intergrated System, Korea Institute of Science and Technology Information, Korean Traditional Knowledge Portal, PubMed, Google Scholar, ScienceDirest, Citation Information by National Institute of Informatics, and China National Knowledge Infrastructure. The 199 traditional medicinal literatures and almost 3000 scientific articles were collected for 27 herbal formulas. The results of our experimental study and the literature analysis were constructed with herbal formula information based on scientific evidence. The conducted information of herbal formulas is provided in books and the internet (https://oasis.kiom.re.kr/) for easy access.
Part Ⅱ. Research and development of concomitant administration on combinatory effect of herbal and Western medicine
The second category team firstly assessed the benefits of herbal medicine via reducing the toxic effect or adverse effect of chemical drug that CYP2E1 is recognized as the enzyme that initiates the cascade of events leading to acetaminophen-induced toxicity. Aconibal protects hepatocytes against acetaminophen-induced toxicity by inhibiting mitochondrial dysfunction. The protective effects of processed Aconibal on acetaminophen-induced hepatotoxicity and determined possible underlying mechanisms or therapeutic target by assessing its effects on mitochondrial dysfunction signaling path-way, such as GSH levels, m, Bcl-2, Bax, and Cyt-C.
And then, this approach was moved to a disease progression models on articular disorders, osteoarthritis or rheumatoid arthritis. Rheumatoid arthritis is systemic and autoimmune disease characterized by chronic inflammation. Methotrexate is often the first line therapy. We investigated the stable modulation of and synergistic to additive effect on TNF-α using aconibal combined with methotrexate. The stable modulation of and synergistic to additive effect on TNF-α were investigated using Aconibal and methotrexate as a combination therapy which revealed the dose reduction percentage around 60%.
Moving to a clinical observational approach, the second category team performed one sample large cohort up to one thousand patients. And their frequency on herb-induced liver injury was 0.6% overall and the profiles were regarding with the prolonged use of chemical drugs; another findings on herb-drug interactions obtained by ecological clinical settings on 10 hospitals. We just stopped the stidu and then we reviewed systematically and quantitatively that pharmacokinetic — pharmacodynamic parameters from randomized controlled trials relating to interactions between herbal medicines and warfarin. It was difficult to determine whether ten herbal medicines had significant effects on the PK/PD parameters of warfarin.
Off target purpose, the second category team summerized the benefits of acupuncture in the setting of post-operative condition that acupuncture is a traditional therapy that stimulates specific acupuncture points on the human body. Herein we present additional clinical data supporting the idea that the effect of acupuncture is dependent on the participant’s pathophysiological conditions. Our finding provides some scientific evidence for the therapeutic action of acupuncture. If acupuncture can improve clinical benefits and patient satisfaction after gynaecological surgery supported by enhanced recovery after surgery (ERAS) programmes. We expected acupuncture to alleviate surgical stress, reduce emetic symptom and accelerate recovery from complications in pre—,intra—,and post-operative phases.
Finally the team approached the interactions between natural product, silymarin and acupuncture in experimental animal model, however, no synergistic phenomena were observed just to confirm silymarin effects on restriction stress which affects liver abnormalities.
Part Ⅲ. Clinical interaction study on concurrent use of Samryungbaekchulsan and Octylonium Bromide for irritable bowel syndrome : safety and effectiveness
3. Outcome
○ Completed to collect subjects of all 4 group (twenty subjects of each group)
○ After further-monitoring and data management, data analysis will be performed.
( 출처 : SUMMARY 12p )
목차 Contents
- 표지 ... 1
- 제 출 문 ... 3
- 보고서 초록 ... 5
- 요 약 문 ... 7
- SUMMARY ... 12
- CONTENTS ... 20
- 목차 ... 21
- 제 1세부과제 한약처방의 과학적 근거 기반 구축 ... 23
- 요 약 문 ... 25
- SUMMARY ... 28
- CONTENTS ... 32
- 목차 ... 33
- I. 제 목 ... 35
- II. 연구개발의 목적 및 필요성 ... 36
- III. 연구개발의 내용 및 범위 ... 39
- IV. 연구개발결과 ... 180
- V. 연구개발결과의 활용계획 ... 722
- 제 2세부과제 한약제제와 의약품의 병용투여 연구개발 ... 725
- 요 약 문 ... 727
- SUMMARY ... 728
- CONTENTS ... 730
- 목차 ... 731
- 제 1장 연구개발과제의 개요 ... 733
- 1. 연구배경 및 목표 ... 733
- 제 2장 연구개발 수행 내용 및 결과 ... 735
- 1. 해당 연도 연구내용 ... 735
- 2. 임상시험 결과 ... 746
- 제 3 장 연구개발결과의 활용계획 ... 748
- 제 4 장 참고문헌 ... 750
- 제 3세부과제 과민성대장증후군에 대한 삼령백출산과 Octylonium Bromide 병용투여 임상 상호작용 연구: 유효성, 안전성 ... 751
- 요 약 문 ... 753
- SUMMARY ... 754
- 1. 연구개발의 필요성 ... 757
- 2. 연구개발 목표 및 내용 ... 765
- 참고자료 ... 789
- 끝페이지 ... 803
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