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Nalbuphie의 병용투여에 의한 morphine의 내성 및 의존성 헝성 저하효과
정면우(Myeon Won Chung),임화경(Hwa Kyung Lim),전용준(Yong Joon Jeon),김혜정(Hye Jung Kim),박인숙(In Sook Park),오우용(Woo Yong Oh),왕소영(So Young Wang),박윤주(Yoonju Park),강주희(Ju Hee Kang),김동섭(Dong Sup Kim),김주일(Joo Il Kim) 대한약학회 2002 약학회지 Vol.46 No.4
Morphine has been used widely on the treatment of many types of chronic pain. However the development of tolerance to morphine by repeat application is a major problem in pain therapy: The purpose of the present study was to investigate whether combined administration of nalbuphine with morphine affects the development of tolerance to and dependence on morphine. We hypothesize that the use of nalbuphine, k-agonist may prove to be useful adjunct therapy to prevent morphine-induced undesirable effects in the management of some forms of chronic pain. Morphine (10 mg/kg) was injected to rats intraperitoneally for 5 days. The variable dose of nalbuphine (0.1,1.0 and 5.0 mg/kg) was administered (I.p.) in combination with morphine injection. The development of tolerance to morphine was assessed by measuring the antinociceptive effect with the Randall-Selitto apparatus. The development of dependence on morphine was determined by the scoring the precipitated withdrawal signs for 20 min after injection of naloxone (10 mg/kg,I.p.). Nalbuphine did not attenuate antinociceptive effect of mofhine in rats. Interesting1y; combined administration of morphine with nalbuphine (100:1) sign- nifcantly attenuated the development of morphine tolerance and dependence. These results suggest that the co-admin-istration of nalbuphine with morphine in chronic morphine treatment can be one of therapies to reduce the development of dependence on morphine.
정수연(Soo Youn Chung),이숙영(Sook Young Yi),류항묵(Hang Mook Rheu),양지선(Ji Sun Yang),유태무(Tae Moo Yoo),김옥희(Ok Hee Kim),노용남(Yong Nam Roh),정면우(Myeon Woo Chung),안미령(Mee Ryung Ahn),최현진(Hyun Jin Choi) 한국응용약물학회 1999 Biomolecules & Therapeutics(구 응용약물학회지) Vol.7 No.2
Bamboo salt has been used for the purpose of precaution and treatment of certain diseases including cancer. Therefore, present study was carried out to ascertain the effects of bamboo salt upon anti-cancer, anti-hypertensive, and anti-diabetic activities as well. To examine the anti-cancer activity of bamboo salt, ICR mice implanted with 1 X 10^6 cells of sarcoma 180 intraperitoneally had been treated daily with bamboo salt A, crude salt, and reagent-grade NaCl (0.2, 1.0, and 2.0 g/kg, p.o.) for 60 days using adriamycin (2 mg/kg) as a positive control. Neither survival rate nor body weight had been significantly influenced by all the treatments indicating that bamboo salt A did not exert the anti-cancer effect on ICR mice. Anti-hypertensive activity was examined in spontaneously hypertensive rats (SHR) which had been administered with bamboo salt A, crude salt, and reagent-grade NaCl (0.1, 0.5, and 1.0 % in drinking water) for 28 days using hydralazin (2 mg/kg) as a positive control. Blood pressure and heart rate were measured at 1, 3, and 4 weeks after the starting date. Significant anti-hypertensive activity was not observed in any treated group compared to the positive control group. In order to determine if bamboo salt had anti-diabetic activity, rats in which diabetes had been induced by streptozotocin (45 mg/kg, i.m.) were treated daily with bamboo salt A, crude salt, and reagent-grade NaCl (0.2, 1.0, and 2.0 g/kg, p.o.) for 28 days using insulin (50 U/kg, s.c.) as a positive control. Blood samples were taken and analyzed at 1, 2, and 4 weeks after the starting date. Bamboo salt did not cause any decreasing effect on the blood glucose levels. These results clearly demonstrated that bamboo salt A did not exert anti-cancer, anti-hypertensive, or anti-diabetic activities in the present experimental animals.
정수연(Soo Youn Chung),최현진(Hyun Jin Choi),정면우(Myeon Woo Chung),안미령(Mee Ryung Ahn),유태무(Tae Moo Yoo),류항묵(Hang Mook Rheu),양지선(Ji Sun Yang) 대한약학회 1999 약학회지 Vol.43 No.4
We investigated the effect of safflower-seed on fracture healing of fracture model in rat. Fracture healing was evaluated by examining the degree of wound healing macroscopically, radiography, bone histomorphometry and biochemical examination. After 1,3,5,7 days, the wound healing was accelerate in safflower-seed diet group. Radiography does not reveal the difference in fracture healing between two groups. After 2 weeks, safflower-seed had a significant, stimulatory effect on external callus formation(p<0.05). But after 4,6,8 weeks, no difference was observed between normal and safflower-seed diet group in callus size. Urinary hydroxyproline, osteocalcin and total alkaline phosphatase decreased significantly (p<0.05) in safflower-seed treated group at 2 week after fracture.
정수연(Soo Youn Chung),박윤주(Youn Joo Park),정면우(Myeon Woo Chung),임화경(Hwa Kyung Lim),강주희(Ju Hee Kang),최기환(Ki Hwan Choi),김주일(Joo Il Kim) 한국응용약물학회 2000 Biomolecules & Therapeutics(구 응용약물학회지) Vol.8 No.4
The present study examined the effect of a methanol extract of Evodiae Fructus on the blood pressure in spontaneously hypertensive rats (SHR). The systolic blood pressure was measured after rats were pretreated with phentolamine, propranolol, or N_ω-nitro-_L-arginine methyl ester(NAME) and subsequently received methanol extract of Evodiae Fructus. In SHR, intraperitoneal administration of methanol extract of Evodiae Fructus (0.5 mg/kg) produced antihypertensive effect that lasted for at least 4 hours. Antihypertensive effect of Evodiae Fructus was more stronger than that with α-adrenergic receptor antagonist phentolamine and was not affected by β-adrenergic receptor antagonist propranolol. The antihypertensive effect of Evodiae Fructus was abolished by pretreatment of NAME. Our findings suggest Evodiae Fructus has an hypertensive effect, which may be mediated through nitric oxide synthesis.
오수유가 N-nitro-L-arginine methyl ester로 유발한 고혈압흰쥐의 심혈관계에 미치는 영향
정수연(Soo Youn Chung),이숙영(Sook Young Yi),유태무(Tae Moo Yoo),안미령(Mee Ryung Ahn),최현진(Hyun Jin Choi),정면우(Myeon Woo Chung),류항묵(Hang Mook Rheu),양지선(Ji Sun Yang) 대한약학회 1999 약학회지 Vol.43 No.3
The present study examined the effect of a methanol extract of Evodiae Fructus on the cardiovascular function in N-nitro-L-arginine methyl ester (NAME)-induced hypertensive Wistar rats after treatment over 6 weeks. In rats treated with NAME, blood pressure, weight of heart, aorta media thickness and media/lumen ratio significantly (p<0.05) increased, whereas coronary flow and heart rate of isolated heart significantly (p<0.05) decreased compared with control group at 6 weeks. In rats treated with NAME and Evodiae Fructus, blood pressure, aorta media thickness and media/lumen ratio signiflcantly(p<0.05) decreased compared with NAME treated group at 6 weeks. These results suggest that Evodiae Fructus is applicable to the treatment of hypertension and vascular hypertrophy.
의약품의 효능별 안전성·유효성 평가에 관한 조사연구(Ⅰ) : 항균제 Antiboiotics
박윤주,최기환,김동섭,박인숙,정면우,임화경,오우용,강주희,박찬웅,김주일 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-
새로운 물질이 개발되어 신약으로 탄생하기까지 많은 시간과 노력, 예산이 필요하다. 최근, 우리 나라에서도, 신약캐발이 어릴고 힘든 분야이지만 새로운 신약개발을 총해 얻어지는 분가가치가 막대함을 인식, 연구에 박차를 가하 있는 실정이다. 본 연구는, 의약품 개발 선진국인 미국 FDA에서 발행하는 참고자료 중 항균제 임상편가에 대한 가이드라인 및 주요 임상적응증별 항균제 기발(지역사획회득성 폐렴, 원내감염성 계렴, 급성기관지염의 2차세균감염, 만성기지염의 급성세균성 악화, 연쇄구균에 의한 인두영 및 편도염 , 단순성 요로감염증, 복합성 요로감염증 및 신우신영, 급성 세균성 부비동옆, 항 바이러스제 개발시 전임상단계에서 고려사항, 항 바이러스제 허가와 된련 잉상적 고려사항, 카레타 괸련 혈류감염)에 있어서의 파이드라인 등의 자료를 소개함으로져, 향후 제약사의 항균제 신약개발 및 허가 신청된 의악품의 전임상차료 및 잉상시험자료의 검토 평가업무에 참고자료로 활용될 수 있을 것이다. Changing or unclear interpretations of clinical trial data needed to demonstrate the effectiveness and safety of antimicrobial drug products have a times led to confusion and frustration on the part of both applicants and division of these drug products reviewers. The FDA published guidance on desing clinical protocols, implementing, and analyzing data from clinical trials for antimicrobial drug products has been presented and additional companion guidances introduced specific issues to individual infections. This document provides applicants and reviewers with minimal information appropriate for the clinical development of routine antimicrobial drug products and identifies issues common to many antimicrobial drug applications. The agency can use the kind of information to determine whether the antimicrobial drug product under study is safe and effective in the treatment of the specific infection studied.
안미령,유태무,정면우,박창신,양지선 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-
간질환 치료약물로 민간에서 사용되고 있는 한방제제인 인진호탕의 안전성 및 유효성을 평가하기 위하여 간질환 동물모질을 이용하여 in vivo에서 효력을 검색하고 간대사 효소의 활성도 변화를 측정하였다. 각종 간 질환은 만성적으로 진행되면써 공통적으로 간겪화에 이르게 된다. 파라서, 본 연구에서는 담도결찰 및 사염화탄소 만성투여로 실험적 간경화를 유도하고, 인진호탕(3.7Sg/kg)과 그 구성 약물인 인진호(3.Og/kg), 치자(1.5g/kg), 대환(0.gg/kg)을 각각 깊주간 투여하여 실험하였다. 간조직내의 hydroxyprolin양 및 iNO즐 발현 과 혈청증 ALT · AST · ALP측정하고, 조직검사를 병행하여 유효성을 평가하였고, 약물대사효소인 cytochrome P4SO의 각 isoByue에 대한 mRNA level 및 효소활성을 측정하여 안전성을 평가하였다. 사염화탄노 투여모킬에서는 인진호탕, 치자, 대황이 hydroxyprolin양을 유의적으로 감소시켰으며 혈청 중 ALT, A끌T, JtLP도 감소시켰다. 이러한 효과는 인잔호탕에서 가장 컸다. 담도결찰모텔에서는 민진호탕과 치자가 hydroxyprotine 양을 유의적으로 감소시켰으며, 혈청 중 ALT도 감소시켰다. 그러나, 조직학적 검사에서는 약물투여에 의한 변화가 뚜편하게 나타나지 않았다. iNOS의 발현은 간경화에 의해서 증가되었으나 약물에 대한 반응은 두 모질에서 파르게 나타났다. 즉 사염화탄소 병태유발 ?1변의 경우는 파물투여에 의한 iNOS발현이 관찰되지 쟈았고, 당도결찰모질에서는 인진호탕에 의한 iNOS발현이 앙린채조 군인 silfmarin투여군과 같이 증가되었다. 또한, 간경화에 외하여 전반절으로 강소된 약물대사효소의 mnNA :1!소활성은 각 isozyme마다 약물에 대하여 파르게 반응하였다. 이 결과로부터 인진호탕 및 치자에 패한 효력을 인 확인하였으며, 각 생약의 투여에 치한 대사효소의 변화를 제시함으로서 간애서 cytochrome P450의 각 isoz『nI 확대사되는 약물과의 병용투여시 적정 용량에 대한 근거를 설정하였다. These studies were conducted to evaluate the efficacy and safety of the Yinchinho-Tang, oriental Hledicine used to treat liver diseases. When it comes to the chronic hepatitisT it usually pro-gressed to cirrhosis. We induced the liver cirrhosis model in rat with chronic trreatrnent of carbon tetra-chloride for 12 weeks or the bile duct double-ligation and scission(BBL/S). After the induction of livercirrhosis, Yinchinho-tang(3.75g/kg) and its ingredients, f feruiriae cafiffaris .H☞rSa(3.Og/kg), eBrOeni3efrHcfue(1.5g/kg) & fAei ffiroma(0.9g/kg) were administered daily for 4 weeks per os. In this study,contents of hydroxyproline(HYP), iNOS mRNA expression aBd histology in liver fissile were measuredas well as the activities of ALT · AST · ALP in serum for efffcacy- Also both the ensyme aetivity andmRNA erpression of enzfme which are responsible for drug metabolim such as Cypfsos were measured.According to our results, in case of a cirrhotie model induced by carbon tetrachloride, both the contentsof HYP in liver and the activities of ALT · AST · ALP in serum were significantly decreased(p<0.01)in each treatment group of Yinchinho-tang, eardeHiae frudHs, and fAei ffiroma. In the other cirrhoticmodel induced by BDL/S, also both the contents of HYP in liver and ALT activity in serum were signifi-cantly decreased(p<0.01) in each treatment group of YiBchinho-tang and eardeniae frHdHs, however,the JLLF activity was significantly decreasrdfp<0.01) only in eardeniae frucfHs. MeaBwhile, it wasfound that there was no siginificant changes in histolegy between the treatment groups. iNOS mRNAexpressilf was increased in cirrhosis but was different between two models when it is treated withdrugs. While there was no finding of observations in iNOS mRlfA expression at each treatment group inmodel of carbon tetrachloride, the treatment of Yinchinho-tallg resulted in the inereased iNOS mRNAexpression in BDL/S, likely in silymarin. The activities of 0yp450s were totally decreased in cirrhosisand different activities of isozymes were noted in the drug trtatrRent groups. To taken all together, wefound there were a partial efficacies of Yinchinho-taBg and farcceniae frHdus. Aslo, it can be postulatedthat the changes in Cypaso isozyme's activitles could be the marker of drug interaction.