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HPLC를 이용한 생체 시료중의 새로운 플라보노이드 유도체인 DA-6034의 분석
이종진,손미원,유무희,장민선,김원배,이강춘 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1
A high performance liquid chromatographic method was developed for the determination of DA-6034 in biological fluids using internal standard. Plasma containing DA-6034 and internal standard was extracted by liquid-liquid extraction at an acidic pH. After evaporation of the organic layer, the drug and internal standard were reconstituted with mobile phase and injected into the column. They were separated by high performance liquid chromatography on inertsil ODS Ⅱ column at 334㎚. The detection limit of DA-6034 in plasma was 0.02㎍/㎖. In this method, the range of recovery and coefficients of variation were 96∼110% and 0.40∼3.78%, respectively. There was no interference from endogenous substances. Urine and bile were analysed using the deproteinization method and the detection limit of DA-6034 was 1㎍/ℓ.
새로운 플라보노이드 유도체인 DA-6034의 TNBS 유발성 염증성대장염 모델에서의 치료효과
손미원,고준일,김희기,장동경,유무희,김원배,이강춘,송인성 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1
The efficacy of DA-6034, a new flavonoid derivative, was investigated in comparison with sulfasalazine in a trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Under light anaesthesia with ether, rats were subjected to intracolonic administration of 30㎎ TNBS in 50% ethanol (0.5㎖) and were then sacrificed at 7 or 21 days after colitis induction. The TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. Moreover, an increase in colonic myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and an elevated colonic leukotriene B_4(LTB_4) level were observed. The colitic rats received DA-6034 (0.3∼30㎎/㎏) or sulfasalazine (50∼100㎎/㎏), prednisolone (0.3∼3㎎/㎏) after the induction of colitis until they were sacrificed. Oral treatment with DA-6034 resulted in significant reductions of macroscopic colonic damage, colonic inflammation. DA-6034 had a more potent effect than sulfasalazine and prednisolone on macroscopic colonic damage, while it has similar effect with prednisolone on the reduction of colonic LTB_4 synthesis and MPO activity. This study show, therefore, that DA-6034 is effective in attenuating the colonic lesion in an TNBS-induced colitis model. Furthermore, the results suggest that the effect of DA-6034 is partially related to its action on LTB_4 synthesis and MPO inhibition.
원외 획득 요로 감염 그람음성 간균에 대한 Cefatrizine-Clavulanic Acid의시험관내 항균력
노경호,염종화,용동은,최성학,이재걸,유무희,이경원,정윤섭 대한진단검사의학회 2005 Annals of Laboratory Medicine Vol.25 No.6
Background : A high proportion of currently isolated gram-negative bacilli are resistant to -lactams by producing -lactamases. -lactam and -lactamase inhibitor combinations have been successfully used to overcome the resistance. In this study, in vitro antimicrobial activity of a new combination, cefatrizine-clavulanic acid, was determined against gram-negative bacilli isolated from community-acquired urinary track infections. Methods : Nonduplicate strains of Enterobacteriaceae, isolated in 2003 from urine specimens of outpatients and inpatients of less than 3 hospital days at Severance Hospital, were tested by the NCCLS agar dilution method. Results : Of a total of 204 isolates, 144 (71%) were Escherichia coli and 30 (15%) were Klebsiella spp. MIC50 and MIC90 of cefatrizine for E. coli were 2 g/mL and 16 g/mL, respectively. MIC90s of both cefaclor and cefoxitin were also 16 g/mL. MIC50 and MIC90 of cefatrizine-clavulanic acid for E. coli were 1 g/mL and 4 g/mL, respectively, which were 1/2-1/4 of those of cefaclor and cefoxitin. For Klebsiella spp., MIC90 of cefatrizine was 4 g/mL with an MIC range of 1->128 g/mL, whereas that of cefatrizine-clavulanic acid was 2 g/mL with an MIC range of 0.5-32 g/mL. In vitro activity of cefatrizine-clavulanic acid was higher than that of cefatrizine. Conclusions : Improved in vitro activity of cefatrizine-clavulanic acid against isolates of E. coli and Klebsiella spp. from community-acquired urinary track infection suggested that the combination is useful for an empirical treatment of the infection. 배경: 최근 분리되는 그람음성 간균 중에는 -lactamase를 생성하는 것이 많아서 penicillin 제와 제1세대 cephalosporin의 유효성이 현저히 적어졌고, 새로운 약제가 개발되어 사용되고 있다. 본연구에서는 제1세대 경구용 cephalosporin인 cefatrizine과 clavu-lanic acid를 병합한 cefatrizine-clavulanic acid 제의 요검체 분리주에 대한 시험관내 항균력을 평가하고자 하였다.방법: 2003년 세브란스 병원에 내원한 외래 및 입원 2일 이내환자의 요 검체에서 분리된 일련의Enterobacteriaceae균종을 대상으로 NCCLS 한천희석법에 따라 항균제 감수성을 시험하였다.결과: 총 204주 중 Escherichia coli와 Klebsiella spp.는 각144주(71%)와 30주(15%)이었다. E. coli에 대한 cefatrizine의MIC50와 M I C90는 각 2 g/mL과 16 g/mL이었고, cefaclor,cefoxitin의 MIC90과 같았다. 반면 cefatrizine-clavulanic acid의MIC50와 MIC90는 각 1 g/mL과 4 g/mL로 cefaclor, cefu-roxime 및 cefoxitin MIC의 1/2-1/4이었고, amikacin과 비슷하였다. Klebsiella spp.에 대한 cefatrizine과 cefatrizine-clavulanicacid의 MIC90는 각 4 g/mL와 2 g/mL이었고, MIC 범위는 각 각 1 ->128 g/mL와 0.5-32 g/mL로 cefatrizine-clavu-lanic acid의 항균력이 좀더 우수하였다. 결론: Cefatrizine-clavulanic acid는 원외 요로감염 환자에서 분리되는 주요 병원균인 E. coli와 Klebsiella spp.에 대한 시험관내 항균력이 우수하여 요로감염증의 경험적 치료항균제로 유용할 것으로 판단된다.
HPLC를 이용한 생체시료중의 새로운 플라보노이드 유도체인 DA-6034의 분석
이종진(Jong Jin Lee),손미원(Mi Won Son),유무희(Moo Hi Yoo),장민선(Min Sun Jang),김원배(Won Bae Kim),이강춘(Kang Chun Lee) 대한약학회 1998 약학회지 Vol.42 No.2
A high performance liquid chromatographic method was developed for the determination of DA-6034 in biological fluids using internal standard. Plasma containing DA-6034 and internal standard was extracted by liquid-liquid extraction at an acidic pH. After evaporation of the organic layer, the drug and internal standard were reconstituted with mobile phase and injected into the column. They were separated by high performance liquid chromatography on inertsil ODS II column at 334 nm. The detection limit of DA-6034 in plasma was 0.02 mcg/ml. In this method, the range of recovery and coefficients of variation were 96-110% and 0.40-3.78%, respectively. There was no interference from endogenous substances. Urine and bile were analysed using the deproteinization method and the detection limit of DA-6034 was 1mcg/l.
새로운 플라보노이드 유도체인 DA-6034의 TNBS 유발성 염증성대장염 모델에서의 치료효과
손미원(Mi Won Son),고준일(Jun Il Ko),김희기(Hee Kee kim),장동경(Dong Kyung Jang),유무희(Moo Hi You),김원배(Won Bae Kim),이강춘(Kang Chun Lee),송인성(In Sung Song) 대한약학회 1998 약학회지 Vol.42 No.2
The efficacy of DA-6034, a new flavonoid derivative, was investigated in comparison with sulfasalazine in a trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Under light anaesthesia with ether, rats were subjected to intracolonic administration of 30mg TNBS in 50% ethanol (0.5ml) and were then sacrificed at 7 or 21 days after colitis induction. The TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. Moreover, an increase in colonic myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and an elevated colonic leukotriene B4 (LTB4) level were observed. The colitic rats received DA6034 (0.3-30mg/kg) or sulfasalazine (50-100mg/kg), prednisolone (0.3-3mg/kg) after the induction of colitis until they were sacrificed. Oral treatment with DA-6034 resulted in significant reductions of macroscopic colonic damage, colonic inflammation. DA6034 had a more potent effect than sulfasalazine and prednisolone on macroscopic colonic damage, while it has similar effect with prednisolone on the reduction of colonic LTB4 synthesis and MPO activity. This study show, therefore, that DA-6034 is effective m attenuating the colonic lesion in an TNBS-induced colitis model. Furthermore, the results suggest that the effect of DA-6034 is partially related to its action on LTB4 synthesis and MPO inhibition.
흰쥐의 Trinitrobenzene Sulfonic Acid ( TNBS ) 유발성 대장염에서 Flavonoids 계 Eupatilin 유도체 DA - 6034 의 효과
장동경(Dong Kyung Chang),진영주(Young Joo Chin),정현채(Hyun Chae Jung),송인성(In Sung Song),김정룡(Chung Yong Kim),손미원(Mi Won Son),유무희(Moo Hi Yoo) 대한내과학회 1998 대한내과학회지 Vol.55 No.3
Objective: In traditional medicine, Artemisia capillaris has been used for treatment of chronic diarrhea. Previously we found Artemisia capillaris had an effect on rats with TNBS-induced colitis. Eupatilin, a kind of fla- vonoids, may be a probable effective component. To evaluate the effect of a eupatilin derivative compound DA-6034 on the rat with TNBS-induced colitis, we perfomed this study, Methods: Colitis was induced with 1ml of 50 mg/ml TNBS mixed with 60 % ethanol (vol/vol) in Sprague Dawley rats. From the next day, 1ml methylcellulose, 1 mg/kg prednisolone, 0.3 or 3 mg/kg of DA-6017 and DA-6034 were administered through once daily for 2 weeks. At 2days, lweek, and 2weeks later, we evaluated the effect by gross damage score (0-10) and measured myeloperoxidase, PGE2, and L from the damaged mucosa. Results: The mean gross damage scores of prednisolone end 3 mg/kg of DA groups were significantly lower than that of a placebo group at 2weeks(0.8, 0.9 vs. 4.0, p<0.05). Myeloperoxidase activities also seemed to be lower in those effective groups but were not statistically significant. LTB4 levels were lower in prednisolone and, 0.3 and 3 mg/kg of DA groups than in a placebo group at 2weeks(7.91, 7.23, and 7.13 vs, 13.90 ng/mg protein, p<0.05), PGE2 levels were decreased in prednisolone and 0.3 mg/kg of DA-6034 groups at 2days. DA17 showed no effects. Conclusions: Eupatilin derivative compound, DA-6034 was effective in rats with TNBS-induced colitis. In that LTE4 leve1 is lowered with some decrease of PGE2 level, this agent probably has an inhibitory effect on arachidonic acid metabolism.