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Kafe 바로가기주관연구기관 | 한국지질자원연구원 Korea Institute of Geoscience and Mineral Resources |
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연구책임자 | 강일모 |
참여연구자 | 김상배 , 이수정 , 김관호 , 김지웅 , 서용재 , 김성원 , 김완태 , 그외 다수 , 노기민 , 이성록 |
보고서유형 | 최종보고서 |
발행국가 | 대한민국 |
언어 | 한국어 |
발행년월 | 2015-12 |
과제시작연도 | 2015 |
주관부처 | 미래창조과학부 KA |
사업 관리 기관 | 한국지질자원연구원 Korea Institute of Geoscience and Mineral Resources |
등록번호 | TRKO201600000618 |
과제고유번호 | 1711027233 |
DB 구축일자 | 2016-04-23 |
키워드 | 스멕타이트,벤토나이트,의약품,고부가가치화,자원탐사smectite,bentonite,pharmaceutics,value-adding process,mineral exploration |
연차 목표
○ 국내 점토광물의 식ㆍ의약품 원료 기술 표준화 수립
○ 감포 벤토나이트 광화대 지질구조도 작성
○ 식ㆍ의약품용 입도제어 기술 개발
○ 점토-유기물 복합체 특성규명/ 기초효능시험
○ 국내 점토광물 특화 발효균 발굴
개발내용 및 결과
○ 국내 점토광물의 식ㆍ의약품 원료 기술 표준화 수립
- 표본시료 300점 이상 확보(시료별 0.3-10kg)
- 중금속 함량, 광물조성, 분광특성 등 기초 분석 결과 취득 및 DB 구축을 위한 메타파일 플랫폼 구축
- 국내ㆍ외 식ㆍ
연차 목표
○ 국내 점토광물의 식ㆍ의약품 원료 기술 표준화 수립
○ 감포 벤토나이트 광화대 지질구조도 작성
○ 식ㆍ의약품용 입도제어 기술 개발
○ 점토-유기물 복합체 특성규명/ 기초효능시험
○ 국내 점토광물 특화 발효균 발굴
개발내용 및 결과
○ 국내 점토광물의 식ㆍ의약품 원료 기술 표준화 수립
- 표본시료 300점 이상 확보(시료별 0.3-10kg)
- 중금속 함량, 광물조성, 분광특성 등 기초 분석 결과 취득 및 DB 구축을 위한 메타파일 플랫폼 구축
- 국내ㆍ외 식ㆍ의약품분야 점토광물 품질기준 도표 제시
- 국내 점토광물 중금속 평가 결과 제시
○ 감포 벤토나이트 광화대 지질구조도 작성
- 효동리 일대 지질구조도 제시
- 시추탐사 수행(작업물량 총 1,000m)을 통한 암상 로깅자료 및 광체분포도 제시
- SHRIMP 지질연대 결과 제시 ◦ 식·의약품용 입도제어 기술 개발
- 중력침강 이용한 최적 입도 선정
- 연속공정을 위한 연속원심분리기 도입/시험운영 중
○ 점토-유기물 복합체 특성규명/ 기초효능시험
- 점토-항생제 복합체 용출특성 규명 및 헬리코박터 제균 효과 제시(in-vitro 실험결과)
- rat, mini-pig를 통한 위벽 도포 효능 제시(in-vivo 실험결과)
○ 국내 점토광물 특화 발효균 발굴
- 국내 벤토나이트 특화 발효균 122종 분리/확보
- 신종 미생물 후보군(12종) 발굴
기대효과
○ 국내 고품위 스멕타이트의 의약품 원료화를 위한 기반 구축
○ 국내 광물성 약재에 대한 개발 가능성 평가
적용분야
○ 국내 자원의 의약품 원료화
○ 국내 자원 고순도, 고부가가치화
○ 국내 스멕타이트 자원을 이용한 신약 개발
Ⅳ. Results
◦ Quality standard of domestic clay minernals for food and pharmaceutic usages
- Montmorillonite, which belongs to a 2:1 layer-type smectite group, is described as dioctahedral smectite at Korea Pharmaceutical Information Center, whereas defined as bentonite in U.S. and European pha
Ⅳ. Results
◦ Quality standard of domestic clay minernals for food and pharmaceutic usages
- Montmorillonite, which belongs to a 2:1 layer-type smectite group, is described as dioctahedral smectite at Korea Pharmaceutical Information Center, whereas defined as bentonite in U.S. and European pharmacopoeias.
- Heavy metals (especially, lead and arsenic) and microbial contamination are critical factors on evaluating the quality of pharmaceutical smectite.
- Because the amount of opalline phase is relatively large in the Korean domestic bentonite ores, opal-reduction techniques are needed.
◦ Exploration of Korean domestic high-quality smectite resources
- The Gampo 46 bentonite mine had been operated as a test bed site for geological and ore-deposit survey and sample collection.
- The matrix of tuff breccia was transformed into smectites at the test bed, and high-grade and quality bentonite formed adjacent to the fault breccia.
- A drone was used to perform 3D aerial survey and geological modeling.
◦ Characterization of the Korean domestic smectites
- Characterizations of mineral assemblies of bentonite ores in Gampo area different, which implies that a detailed mineralogical study should be carried out for finding pharmaceutical-grade bentonites.
- High-grade bentonites of the test bed consist mainly of Ca-type smectites and opalline phases and plagioclases occur in minority.
- When comparing commercial bentonites used for gastrointestinal drugs, opal-reduction techniques should be needed for purifying the Korean domestic bentonites with a large amount of opalline phase.
◦ Purification of the Korea domestic bentonites
- The bentonite samples were separated using a sedimentation method, subsequently fractional yield, analyzing mineral assemblage, montmorillonite content, and cation exchange capacity.
- The opalline phases could not be separated using a simple sedimentation method.
- A novel method to separate the opalline phase from smectite by combining ultrasonic dispersion and ultra-fine particle separation are developed.
◦ Formation of antibiotics-intercalated composites
- The composite materials were synthesized using two kinds of absorbable antibiotics (amoxicillin and clarithromycin) and three of non-absorbable ones (gentamicin, tobramycin, and netilmicin).
- As a result of X-ray diffraction analyses, both absorbable and non-absorbable antibiotics were intercalated into the smectite interlayers.
- The in-situ columnar release test was carried out for the clarithromycin-smectite composite materials.
◦ Basic test on the effect of smectites and composites
- Solid and liquid medium tests were performed to investigate the effect of amoxicillin-smectite mixture on the genesistasis of Helicobactor pylori.
- The genesistasis effect of smectite itself was investigated.
- Developing clarithromycin-smectite composite with clarithromycin 205.09 mg/g.
- 90% and 70% of Clarithromycin was released within 60 min by sequential releasing batch test using pH=1.2 and 7.4 solutions, respectively.
- More than 60% area of gastric wall was coated with antibiotic-intercalated smectite composite at 1 hour after administration in Rat study.
- In Mini-Pig study, the samples were diffusely distributed at gastric body area in 1 hour after administration.
- Twenty H. pylori strains were isolated and derived from 172 patients.
- E-test and disk diffusion tests were conducted to the standard strain and clinical strains of H. pylori. There was no isolated resistant strain.
- Antibiotic-intercalated smectite disc has produced similar antimicrobial effect compared with matched antibiotic disc. It means antibiotics were well released from the composite in the culture media.
◦ Microbiological analysis of clay mineral sources
- Massive sequencing analysis of 15 clay mineral sources revealed that microorganisms in the phylum proteobacteria and firmicutes were the dominant microbial members and total 403 genus including 2579 bacterial species were identified in the NGS analysis.
- TSA (for the isolation of Bacillus sp.) and MRS (for the isolation of Lactic acid bacteria) media were used to isolate applicable microbes in the fermented food from clay minerals. 21 Bacillus strains and various bacterial species in the genus Paenibacillus, Lysinibacillus, Arthrobater were isolated from clay minerals and, among these microbes, unreported 6 strain were newly isolated.
- The clay minerals provided by KIGAM showed a growth inhibitory activity against food spoilage microorganisms and also affect to the enzymatic reactions of industrial enzymes including cellulase, protease, and lipase. It is suggested that clay minerals could be used as fermentation modifier for Korean fermented foods.
- Clay minerals also showed health beneficial effects on animal model. One type of clay minerals showed a anti-obesity effect in animal experiments using DIO (Diet induced obesity) mice and Two types of clay minerals showed mitigative effect in the symptoms of inflammatory bowel disease in IBD mice animal studies.
◦ Clinical demonstration of the domestic smectite
- We investigated in vitro and in vivo models to evaluate the safety and efficacy of bentonite. In addition, we performed an animal study to test its activity and kinetics in the gastrointestinal tract such as mucoadhesion, duration of action and residence time.
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