디클로페낙 프로드럭들의 흰쥐 피부 투과

도희정,조원제,용철순,이치호,김대덕 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Various alkyl ester prodrugs of diclofenac were synthesized in order to investigate the relationship between their skin permeation characteristics and physicochemical properties. Solubility in various vehicles was measured at room temperature. I -Octanol/water partition coefficients (Log P) and capacity factors (k') were measured to determine the lipophilicity of the prodrugs. Stability of prodrugs in the skin extract and homogenate was also investigated before conducting the skin permeation studies. Increases in the Log P and capacity factor values were observed when alkyl esters of diclofenac were prepared. Since the aqueous solubility of the prodrugs was not high enough, they were saturated in propylene glycol (PG) for skin permeation studies. Prodrugs were rapidly metabolized to diclofenac, both in skin homogenate and in dermal extract of skin. The skin permeation rate of alkyl ester prodrugs was significantly higher than diclofenac with shorter lag time. Moreover, a parabolic relationship was observed between the permeation rate and the log P values of prodrugs, and the maximum flux was achieved at a log P value of around 4.0.

디클로페낙 프로드럭들의 흰쥐 피부 투과

도희정,조원제,용철순,이치호,김대덕 영남대학교 약품개발연구소 2002 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

Various alkyl ester prodrugs of diclofenac were synthesized in order to investigate the relationship between their skin permeation characteristics and physicohemical properties. Solubility in various vehicles was meastured at room temperature. 1-Octanol/water partition coefficients (Log P) and capacity factors (k") were measured to detemine the lipophilicity of the prodrugs. Stability of prodrugs in the skin extract and homogenate was also investigated before conduction the skin permeation studies. Increases in the Log P and capacity factor values were observed when alkyl esters of diclofenac were perpared. Since the aqueous solubility of the prodrugs was not high enough, they were saturated in propylene glycol (PG) for skin permeation studies. Prodrugs were rapidly metabolized to diclofenac, both in skin homogenate and in dernal extract of skin. The skin permeation rate of alkyl ester prodrugs was significantly higher than diclofenac with shorter lag time. Morecover, a parabolic relationship was observed between the pemeation rate and the log P values of prodrugs, and the maximum flux was achieved at a log P value of around 4.0.

디클로페낙 프로드럭들의 흰쥐 피부 투과

도희정,조원제,용철순,이치호,김대덕 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

Various alkyl ester prodrugs of diclofenac were aynthesized in order to investigate the relationship between their skin permeation characteristics and physicochemical properties. Solubility in various vehicles was measured at room lemperature. I-Octanol/water partition coefficients (Log P) and capacity factors (k^(+)) were measured to detenmine the lipophilicity of the prodrugs. Stability of prodrugs in the skin extract and homogenate was also investigated before conducting the skin penmeation studies. Increases in the Log P and capacity factor values were observed when alkyl esters of diclofenac were prepared. Since the aqueous soubility of the prodrugs was not high enough, they were saturated in propylene glycol (PG) for skin permeation studies. Prodrugs were rapidly metabolized to diclofenac, both in skin homogenate and in dermal extract of skin. The skin permeation rate of alky1 ester prodrugs was significantly higher than diclofenac with shorter lag time. Moreover, a parabolic relationship was observed between the permeation rate and the log P values of prodrugs, and the maximum flux was achieved at a log P value of around 4.0.

한국판 해밀턴 우울증평가척도(K-HDRS)의 확인적 요인 분석

박혜원,이은호,김도관,유범희,이동수,김지혜 大韓神經精神醫學會 2009 신경정신의학 Vol.48 No.1

Objectives The present study was conducted to examine the factor structure of a Korean version of the Hamilton Depression Rating Scale (K-HDRS), and we did so by performing a confirmatory factor analysis (CFA). Methods The data from the 17-item K-HDRS data was obtained from 319 South Koreans who met the DSM-IV Criteria of Major Depressive Disorder. We examined the fit of ten competing models. The CFAs were evaluated in their original first-order structures and in their hierarchically related counterparts. Results The alternative models obtained unsatisfactory fit indices, although the five-factor inter-correlated model (model 5a) demonstrated a relatively good fit to the data. The model 5a also performed better than its hierarchically related counterpart (model 5b). The Modification Indices (MIs) were used to provide a more satisfactory account of the data. The Mls suggested correlations between the unique variances of items (item 1 & 3, item 10 & 15), and these parameters were added to the model 5a. After introducing minor modifications, the 'final' model (5m) yielded an improved model fit. Conclusion This study suggests that the symptoms of depression, as assessed by the K-HDRS, cluster into five factors : anhedonia/retardation, guilt/agitation, bodily symptoms, insomnia and appetite. This study provides evidence for the cross-cultural generalizability of the HDRS, although some refinement of the scale is still required.

척수 동정맥 기형 : 증례보고 Case Report

최원철,강재규,도종웅,정현태,문성수 최신의학사 1991 最新醫學 Vol.34 No.12

栽培法의 差異가 水稻의 收量 및 米質에 미치는 影響

정원복,김도훈,정대수,김현경 東亞大學校附設 農業生命科學硏究所 1999 農業生命資援硏究 Vol.8 No.1

水稻의 早期栽培에 따른 品種別 栽植距離와 株當苗數가 生育 및 收量에 미치는 影響과 栽培時期에 따른 米質을 변화를 比較코저 小白벼, 農白벼, 福光벼, 道奉벼, 太白벼, 및 伽倻벼를 公試하여 實施한 試驗結果는 다음과 같다. 株當穎花數는 穎植(27×17cm)며 株當 3苗植인 處理區에서 가장 많았고, 10a當 收量은 密植(27×13cm) 및 株當 5∼7苗植인 處理區에서 가장 많았다. 10a當 收量 및 藁重, 穗數間에 有意的인 正의 相關關係가 認定되었다. 또한 Amylose含量은 普通期栽培보다 早期栽培에서 적게 나타났고, 品種間에는 福光벼가 가장 낮았고, Alkali崩壞度는 普通期栽培보다 早期栽培에서 낮았고, 品種間에는 伽倻벼가 높게 나타났다. A study was presented to analyze rice quality and to number of seedlings per hill and their spacing on growth and yield in various varieties of early planted rice; Sobeag, Nongbeag, Dobong, Taebeag and Gaya. There was a higher number of spikelets in wide spacing than in narrow spacing, and the number from from 3 seedlings per hill was greater than the one from 5 or 7 seedlings per hill. In grain yield per 10 areas, there was a higher yield in narrow spacing than in wide spacing, and the on from the block of the 5 or 7 seedlings per hill was greater than the one from the block of 3 seedlings per hill. There was a significant positive correlation among grain yield per 10 areas, straw weigh and the number of panicles. Amylose contents were lower in early planted rice than in ordinarily planted rice. The Boggawng variety showed lowest amylose contents among the varieties used in this experiment. Alkali digestibility values were lower in early planted rice than in ordinarily planted rice. The Gaya variety showed highest alkali digestibility values among the varieties used in this experiment.

다양한 비스테로이드성 소염진통제의 쥐 피부 투과

김민정,도희정,조원제,용철순,최한곤,이치호,김대덕 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.4

Rat skin permeation of various nonsteroidal antiinflammatory drugs (NSAIDs) was investigated in vitro using Franz diffusion cell at 37℃. The effect of various skin permeation enhancers was also observed as a preliminary study of developing transdermal delivery systems of NSAIDs. Lipophilicity of NSAIDs was determined from the partition coefficient (log P) in 1-octanol/water and 1-octanol/IPB mutual-saturated solutions. The solubility was determined in water, isotonic phosphate buffer (IPB), and propylene glycol (PG) at 37℃. The rat skin permeation rate of acetaminophen, piroxicam, and aceclofenac was almost negligible, although they were saturated in PG. Addition of 1 % permeation enhancer increased the permeation rate of ketoprofen, ketorolac, and diclofenac. However, the skin permeation rate of ibuprofen did not increase with the addition of various enhancers. Among the permeation enhancers tested, oleic acid was the most effective for various NSAIDs. Based on the daily dose, lipophilicity, and the skin permeation rate achieved in this study, ketoprofen and ketorolac seem to be the most promising drug candidates for transdermal delivery systems, especially when formulated with unsaturated fatty acids, such as oleic acid.

기분 장애 환자에서 나타나는 불특정 CAG 삼핵산 반복서열의 확장

손성은,임신원,이소영,황혜진,진동규,박정의,김도관,김이영 대한신경정신의학회 2000 신경정신의학 Vol.39 No.2

연구목적: 기분장애는 그 원인과 발생기전은 아직 밝혀져 있지 않고 있지만, 과거부터 유전적 요인이 질병의 발생과 중요한 연관성을 가지고 있다고 알려져 있다. 특히 양극성 정동장애는 가족력이 있는 경우에 발병될 가능성이 높고, 같은 가족 내에서 발생했을 때 세대가 내려감에 따라서 발병시기가 점차 빨라지며 증세가 심해지는 경향이 있어서 그 유전적 배경에 대해 많은 의문이 있어 왔다. 연구자들은 다양한 증상의 기분장애 환자들의 DNA에서 불특정 CAG 삼핵산 반복(trinucleotide repeat. TNR) 정도를 분석함으로써 TNR 확장이 기분장애의 유전과 관련되는지 살펴보았다. 방법: 환자 군은 DSM-Ⅲ-R 진단기준에 의거하여 양극성 정동장애(N=55), 주요우울장애(N=67) 환자들을 선발하였다. 정상인(N=89)은 정신과적 병력이 없고 다면성 인성검사상 정상의 profile을 나타내는 병원 종사자, 학생 및 건강의학센타 방문자들 중 선발하였다. TNR의 확장은 genomic DNA를 순수분리한 후, (CTG)₁□의 oligonucleotide를 □-□□P-ATP로 방사선 표지하여 반복서열 확장 탐지법(repeat expansion detection)으로 측정하였다. 집단간의 비교를 위해 Mann-Whitney U 검증을 실시하였다. 결과: DNA에서 관찰되는 불특정 CAG 삼핵산 반복 길이의 평균은 양극성 정동장애에서 169.8bp(S.D=58.6), 주요우울장애에서 167.5bp(S.D=63.9)로서 대조군 178.7bp(S.D=56.5)과 비교하였을 때 유의미한 차이는 관찰되지 않았다. 각각의 환자군을 가족력이 있는 군과 없는 환자군으로 나누어 대조군과 비교하였을 때도 유의미한 차이는 관찰되지 않았다. 결론: 불특정 CAG 삼핵산 반복서열 확장이 양극성 정동장애 환자와 주요우울장애 환자들의 유전 양식에 영향을 미친다는 가설을 뒷받침하지 않는다. Objectives: The genetic facotrs have been suggested for the etiology of mood disorders but the mode of inheritance is complex. Increased severity and an earlier onset of the bipolar and major depressive disorder over generations within families(Anticipation) were reported. In order to test the hypothesis that trinucleotide repeat expansions underlie the genetic basis of Bipolar and major depressive disorders, we have analyzed the extent of CAG reapeats in genomic DNA from mood disorder patients. Methods: 55 bipolar disorder, 67 major depressive disorder patients were recruited accord-ing to the DSM-Ⅲ-R criteria. 89 normal controls were recruited from the medical personnel, students and the visitors to the health services center who had no history of psychiatric illness and show normal profile of MMPI. The genomic DNA of patients and controls was analyzed by use of the (CTG)□ oligonucleotide and the repeat expansion detection(RED) method. The Mann-Whitney U test was used to compare the distribution of the number of CAG repeats among the groups. Results: when the bipolar disorder, major depressive disorder patients were compared with the control group, no significant differences were observed. Conclusions: Our results do not support the hypothesis that expanding CAG repeats are causing the observed genetic anticipation in bipolar disorders and major depressive disorders.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

Clopidogrel에 의해 발생된 전신 염증 반응 증후군 1례

김민환,김종훈,박경일,박혜연,황철웅,김의석,도준형,남궁준,이성윤,이원로 白中央醫療院 2005 仁濟醫學 Vol.26 No.1

Clopidogrel bisulfate, a widely used inhibitor of platelet aggregation, is considered at least as safe as aspirin. We describe a 61 year old male patient who developed a systemic inflammatory response syndrome consisting of high fever, rash, chills, impaired liver function, and mild leukopenia after receiving clopidogrel after coronary angiography and stent implantation. The reaction resolved promptly after withdrawal of the drug, thus making the diagnosis of a clopidogrel induced reaction highly probable.