[보고서]진해거담 한약제제 GHX02 개발연구

박양춘

보고서 정보

주관연구기관

한국한의학연구원
Korea Institute of Oriental Medicine

연구책임자

박양춘

참여연구자

채성욱 , 박병욱

보고서유형

최종보고서

발행국가

대한민국

언어

한국어

발행년월

2019-11

과제시작연도

2019

주관부처

과학기술정보통신부
Ministry of Science and ICT

등록번호

TRKO202000003258

과제고유번호

1711100477

사업명

한국한의학연구원연구운영비지원(R&D)(주요사업비)

DB 구축일자

2020-05-09

키워드

진해거담제.한약제제.임상시험.임상시험허가신청.기관지염.Antitussive and expectorant drug.bronchitis.herbal medicine.clinical trial.investigational new drug application.

DOI

https://doi.org/10.23000/TRKO202000003258

표 2008년~2015년 외래 다발생 질병 변화추이 (단위: 천명)
표 만성기관지염과 COPD 및 천식과의 관계(A). 미국 주요 만성질환 사망률 변화(B)(Global Initiative for Chronic Obstructive Pulmonary Disease NHLBI/WHO workshop report)
표 COPD에서 기도 점액 과다분비의 원인. PEF: peak expiratory flow. (Kim V et al. Am J Respir Crit Care Med 2013;187(3):228-37.)
표 미세먼지로 발생할 수 있는 각종 (환경부 http://www.me.go.kr/issue/finedust/) 질병
표 GHX02 구성 및 임상활용 제형
표 호흡기 의약품 시장의 성장 (From Teva)
표 COPD 국제시장 규모, 2012-2019 (From GBI Research)
표 COPD에 처방되는 약의 구성비 (From Datamonitor 2005)
표 Whole body plethysmography를 통한 기침 측정
표 Effects of GHX02 on citric acid–induced cough in unanesthetized guinea pigs. The animals were exposed to a nebulized aqueous solution of citric acid (0.4 M) for 30 min (control experiments); 48 hour later, they were exposed under similar conditions to citric acid, 1 hour after an administration of saline or GHX02. Results are expressed as cough number in control experiments, after saline or GHX02 administration. Values are means 8 SEM. Number of animals used for each group was 8-10
표 Increase of GHX02 on phenol red secretion of in ICR mice. ICR mice were divided into ten groups (n=10–12 per group), and were orally administered saline, ambroxol (250 mg/kg/day), composition herb or GHX02 (100, 200, 400 mg/kg/day)
표 Streptococcus pneumoniae에 대한 GHX02의 항균 효과 실험
$Antimicrobial activities of each solvent fraction from GHX02 against bacteria$ 표 Antimicrobial activities of each solvent fraction from GHX02 against bacteria
표 Minimum inhibition concentration of GHX02 extract of streptococcus pneumoniae
표 Raw 264.7 세포에서 GHX02 구성개별약물과 과루행련환, GHX01, GHX02의 농도별로 처리 후 세포독성측정 결과
표 RAW 264.7 세포에서 GHX02 구성개별약물과 과루행련환, GHX01, GHX02의 농도별로 처리 후 NO 생성량 측정
표 RBL-2H3 세포에서 GHX02 구성개별약물과 GHX02의 농도별로 처리 후 leukotriene 생성량 측정
표 RBL-2H3 세포에서 GHX02 구성개별약물과 GHX02의 농도별로 처리 후 PGE2 생성량 측정
표 RBL-2H3 세포에서 GHX02 구성개별약물과 GHX02의 농도별로 처리 후 ELISA를 통하여 cytokine 측정 (A)IL-4, (B)IL-13
표 Effect of Trichosanthis Fructus, Armeniacae amarum Semen, Coptidis Rhizoma, Scutellariae Radix and GHX02 extract on histamine releasing in compound 48/80-stimulated HMC-1 cells. The cells (2 × 105 cells/㎖) were incubated with Trichosanthis Fructus, Armeniacae amarum Semen, Coptidis Rhizoma, Scutellariae Radix and GHX02 extract in the presence or absence of compound 48/80 (10 ㎍/㎖) for 30 min. The concentration of histamine was determined in culture supernatant by enzyme-immuno assay (EIA). Three independent experiments were performed, and the data shown indicate the mean±SEM * : Significantly different from the Control group (* p<0.05, ** p<0.01, *** p<0.001)
표 Effects of GHX02 on the acute airway inflammation induced by ammonia liquor in mice, taking the number of leukocytes in BALF as an indicator. GHX02 mixture in the ratio were administrated at 400, 200, 100 mg/kg, respectively. Prednisone acetate (10 mg/kg) was taken as a positive control, and the vehicle was administered with 0.5% CMC-Na. Values were expressed as mean ± SEM (n¼9-10). * : Significantly different from the Control group (* p<0.05, ** p<0.01, *** p<0.001)
표 Airway resistance of carbachol induced guinea pigs model. After medication in the on GHX02 and composition group. Carbachol were treated to 50μ g/ml per animal. Values are means±SEM. Number of animals used for each group was 8-10. * : Significantly different from the control group (* p<0.05, ** p<0.01, *** p<0.001)
표 Schematic diagram of cigarette smoke extract-induced chronic obstructive pulmonary disease in mice
표 Effect of GHX02 on cytospin image of BALF in COPD mice. Mice were challenged by aspiration of LPS+CSE (Control), and then treated with Dexa (dexamethasone 3 ㎎/㎏), TF (Trichosanthis Fructus 200 ㎎/㎏), AS (Armeniacae amarum Semen 200 ㎎/㎏), CR (Coptidis Rhizoma 200 ㎎/㎏), SB (Scutellaria baicalensis 200 mg/kg) and GHX02 (400, 200, 100 ㎎/㎏) for 21 days (n=8). All values are mean±SEM. * : Significantly different from the Control group (* p<0.05, ** p<0.01, *** p<0.001)
표 Effects of GHX02 on histopathological changes and histology scores in the lung of a CSE/LPS-induced murine model of chronic obstructive pulmonary disease. Untreated mice received the vehicle, whereas model mice were induced by intratracheal injection of CSE/LPS and then treated with the vehicle (CTL), Dexa (dexamethasone 3 ㎎/㎏), TF (Trichosanthis Fructus 200 ㎎/㎏), AS (Armeniacae amarum Semen 200 ㎎/㎏), CR (Coptidis Rhizoma 200 ㎎/㎏), SB (Scutellaria baicalensis 200 mg/kg) and GHX02 (400,200,100 ㎎/㎏) for 21 days. Lungs were fixed, sectioned, and stained with hematoxylin and eosin (H&E) and Masson's trichrome (M-T) stains. (A) Representative sections from each treatment group are shown. (B) Quantitative analysis of the degree of lung tissue damage in the sections. Data are from individual mice, with the arithmetic means shown in the histogram. All values are mean±SEM. * : Significantly different from the Control group (* p<0.05, ** p<0.01, *** p<0.001)
표 Effect of GHX02 on TNF-α, IL-17A , MIP2 and CXCL-1 production of BALF in COPD mice. Mice were challenged by aspiration of LPS+CSE (Control), and then treated with Dexa (dexamethasone 3 mg/kg), TF (Trichosanthis Fructus 200 mg/kg), AS (Armeniacaeamarum Semen 200 mg/kg), CR (Coptidis Rhizoma 200 mg/kg), SB (Scutellaria baicalensis 200 mg/kg) and GHX02 (400, 200, 100 ㎎/㎏) for 21 days (n=8). * : Significantly different from the Control group (* p<0.05, ** p<0.01, *** p<0.001)
표 Airway accumulation of neutrophils/eosinophils and infiltration of inflammatory cells into the PBMC, lung and BALF. Mice were challenged by aspiration of LPS+CSE (Control), and then treated with Dexa (dexamethasone 3 ㎎/㎏), TF (Trichosanthis Fructus 200 ㎎/㎏), AS (Armeniacae amarum Semen 200 ㎎/㎏), CR (Coptidis Rhizoma 200 ㎎/㎏), SB (Scutellaria baicalensis 200 mg/kg) and GHX02 (400,200,100 ㎎/㎏) for 21 days (n=8). * : Significantly different from the Control group (* p<0.05, ** p<0.01, *** p<0.001)
표 Quantification of Immune Cell Subtypes in the Lungs and BALF of Mice by FACS Analysis
표 Schematic diagram of ovalbumin sensitization asthma in mice
표 Change of airway hyperresponsiveness with MCH concentration. OVA (Control), and then treated with Dexa (dexamethasone 3 ㎎/㎏), TF (Trichosanthis Fructus 200 ㎎/㎏), AS (Armeniacae amarum Semen 200 ㎎/㎏), CR (Coptidis Rhizoma 200 ㎎/㎏), SB (Scutellaria baicalensis 200 mg/kg) and GHX02 (400,200,100 ㎎/㎏) for 21 days (n=4). All values are mean±SEM. * : Significantly different from the Control group (* p<0.05, ** p<0.01, *** p<0.001)
표 The number of total cells in bronchoalveolar lavage fluid and Lung. Mice were challenged by aspiration of OVA (Control), and then treated with CsA (cyclosporin A 10 mg/kg) and GHX02 (200,100 ㎎/㎏) for 44 days (n=8). * : Significantly different from the Control group (* p<0.05, ** p<0.01, *** p<0.001)
표 Effects of GHX02 on OVA-specific IgE release in OVA challenged allergic mouse model. Mice were treated with the GHX02 extract (200, 100㎎/㎏) for 13 weeks. Balb/c mice were challenged with OVA as described in the Experimental section. Blood samples were collected after 2 weeks and 14 weeks for OVA-specific IgE measurement and serum was prepared. Values are expressed as mean±S.E.M (n=8) (**p<0.01, *** p<0.001 versus the OVA_CTL group)
표 Change of cytokine levels in bronchoalveolar lavage fluid. Mice were treated with the GHX02 extract (200, 100㎎/㎏) for 13 weeks. Balb/c mice were challenged with OVA as described in the Experimental section. * : Significantly different from the Control group (* p<0.05, **p<0.01, *** p<0.001 versus the OVA_CTL group)
표 Effect of GHX02 on histologic markers of airway inflammation in lung tissue of OVA-induced mice. (A) M-T, and PAS staining of lung sections from normal and asthmatic mice treated with OVA (control), GHX02 (200, 100 mg/kg). PAS-positive cell number (B) were quantitated. M-T: Masson’s trichrome; PAS: periodic acid-Schiff. Results are expressed as mean ± SEM (n = 8 mice per group). * : Significantly different from the Control group (** p<0.01, *** p<0.001)
표 Effect of GHX02 on cytospin image of BALF in OVA-induced mice. Mice were treated with the GHX02 extract (200, 100㎎/㎏) for 13 weeks. Balb/c mice were challenged with OVA as described in the Experimental section
표 Experimental schedule for the PM10 plus DEP (PMD) induced mouse model
표 Inhibition of infiltrated granulocytes by GHX02 extracts in airway of PMD induced mouse model. (A) Suppressed neutrophilia in BAL Fluid. (B) Photomicrograph of BAL Fluid cytospins from PM10D-induced mice. The granulocytes infiltrated to BAL were estimated by Diff-Quik staining. Data are shown as mean ± SEM of each group (n=8 per group). ###p < 0.001 versus the BALB/c_normal group, ***p < 0.001 versus the PM10D control group mice
표 Amelioration of clinical signs by GHX02 extracts in airway tissue from PMD-induced mice models. Thickness of alveolar wall was measured by H&E staining, M-T and PAS staining assay. (A) Effect of GHX02 treatment on lung histopathology in PM10D-induced mice. Lungs were fixed, sectioned, and stained with hematoxylin and eosin (H&E), Masson's trichrome (M-T) stains and PAS stains. Representative sections from each treatment group are shown. (B) Quantitative analyses of the degree of lung tissue damage in the sections. Data are from individual mice, with the arithmetic mean points shown in the histograms. Data are shown as mean ± SEM of each group (n=8 per group). ###p < 0.001 versus the BALB/c_normal group, ***p < 0.001 versus the PM10D_control group mice
표 Reduced expression of chemokines by GHX02 extracts in airway of PM10D-induced mouse models. Production of CXCL proteins (A), MIP2 (B), TNF-α (C), and IL-17 (D) in BALF was measured by ELISA. Data are shown as mean ± SEM of each group (n=8 per group). #p < 0.05 and ###p < 0.001 versus the BALB/c_normal group, *p < 0.05, **p < 0.01 and ***p < 0.001 versus the PM10D_control group mice
표 Inhibition of infiltrated granulocytes by the GHX02 extracts in airway of PM10D-induced mouse model. The total BAL (A), and lung (B) cells were counted using flow cytometry. Data are shown as mean ± SEM of each group (n=8 per group). ##p < 0.01 versus the BALB/c_normal group, *p < 0.05 and ***p < 0.001 versus the PM10D_control group mice
표 Quantification of Immune Cell Subtypes in the Lungs and BALF of Mice by FACS Analysis
표 임상시험 대상자 모집 포스터
표 Subject Enrollment Status
표 Monitoring visit report (A) and audit report (B)
표 개발계획(A) 및 시험자 자료집(B)
표 임상시험 피해자 보상에 관한 규약(A) 및 시험대상자 동의서 서식(B)
표 Single-dose oral toxicity of GHX02
표 Body weight changes of male and female
표 Effect of GHX02 on the weekly food and water consumption
표 Urinalysis and sediments in male and female rats
표 Hematological values of GHX02 in male rats
표 Hematological values of GHX02 in female rats
표 Serum biochemical values of GHX02 in male rats
표 Serum biochemical values of GHX02 in female rats
표 Absolute and relative organ weights in male rats
표 Absolute and relative organ weights in female rats
표 Necropsy findings in male and female rats
표 Bacterial reverse mutation test
표 In vitro chromosome aberration test
표 In vivo micronucleus test
표 In vivo comet assay
표 구성성분별 HPLC fingerprint 및 한약제제 분석
표 Identification of the marker component of GHX02
표 GHX02 inhibited TNF-α-induced inflammatory mediator production in NHBE cells
표 GHX02 inhibited TNF-α-induced MARK phosphorylation
표 GHX02 inhibited TNF-α-induced STAT-3 and ATF=2 activation
표 GHX02 activated HO-1 expression through the Nrf-2 pathway in NHBC

과제명(ProjectTitle) :	-
연구책임자(Manager) :	-
과제기간(DetailSeriesProject) :	-
총연구비 (DetailSeriesProject) :	-
키워드(keyword) :	-
과제수행기간(LeadAgency) :	-
연구목표(Goal) :	-
연구내용(Abstract) :	-
기대효과(Effect) :	-

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 제목(한글), 저자명(한글), 발행일자, 전자원문, 초록(한글), 초록(영문) 관리번호, 제목(한글), 제목(영문), 저자명(한글), 저자명(영문), 주관연구기관(한글), 주관연구기관(영문), 발행일자, 총페이지수, 주관부처명, 과제시작일, 보고서번호, 과제종료일, 주제분류, 키워드(한글), 전자원문, 키워드(영문), 입수제어번호, 초록(한글), 초록(영문), 목차
저장형식	Text(ASCII format) Excel format
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증

진해거담 한약제제 GHX02 개발연구
Development of new Korean medicine GHX02 as antitussive and expectorant agent 원문보기

초록 ▼

Abstract ▼

목차 Contents

표/그림 (67)

표/그림 (67)

참고문헌 (25)

연구과제 타임라인

관련 콘텐츠

원문 보기

이 보고서와 함께 이용한 콘텐츠

AI-Helper ※ AI-Helper는 오픈소스 모델을 사용합니다.

선택된 텍스트

연합인증

진해거담 한약제제 GHX02 개발연구 Development of new Korean medicine GHX02 as antitussive and expectorant agent 원문보기

초록 ▼

Abstract ▼

목차 Contents

표/그림 (67) 모든 표/그림 보기

표/그림 (67) 슬라이드로 보기

참고문헌 (25)

연구과제 타임라인

전체(0) 논문(0) 특허(0) 보고서(0)

전체(0) 논문(0) 특허(0) 보고서(0)

관련 콘텐츠

원문 보기

이 보고서와 함께 이용한 콘텐츠

AI-Helper ※ AI-Helper는 오픈소스 모델을 사용합니다.

선택된 텍스트

진해거담 한약제제 GHX02 개발연구
Development of new Korean medicine GHX02 as antitussive and expectorant agent 원문보기

표/그림 (67)

표/그림 (67)