항정신병약물 사용 중인 정신분열병 환자에서 올란자판으로의 교체 방법에 관한 연구(II) : Comparison of Safety 안전성 비교

안용민,권용실,권준수,민성호,박두병,양문정,소형석,송종호,신윤식,우행원,유범희,이홍석,정한용,한창환,김용식 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.5

연구목적: 이 다기관 공동임상연구는 사용 중인 항정신병약물을 ’직접 교체 방법’또는 ’시작-감량 교체 방법’중 한 가지 방법으로 올란자핀으로 교체한 후, 안정성 측면에서 두 교체 방법 간의 비교와 교체후의 변화를 관찰하기 위한 것이다. 방법: 국내 13개 병원의 입원 및 외래에 내원한 환자들 중 ICD-10 지단기준으로 정신분열병에 해당되며, 임상적으로 항정신병약물 교체가 필요한 환자를 대상으로 하였다. 두 가지 교체 방법 중 한 가지를 무작위로 피험자에 적용하였으며, ’직접 교체 방법’에 배정된 경우에는 사용중인 항정신병약물을 일시에 중단하고 10㎎의 올란자핀을 바로 투여하였고, ’시작-감량 교체 방법’에 배정된 경우는 10㎎의 올란자핀 투여하고 2주에 걸쳐서 기존 약물을 감량하여 중단하였다. 올란자핀 사용기간은 총 6주이며, 용량은 5∼20㎎ 범위로 제한하였다. 한정성 평가를 위해서 체중, 생명징후, 자발적인 이상반응 복, 실험실 검사 그리고 Simpson-Angus Scale(SAS), Barnes akathisia rating scale(BARS), Abnormal involuntary movement scale(AIMS). Liverpool University neuroleptic side effect rating scale(LUNSERS)등을 이용하였다. 결과: 총 103명의 정신분열병 환자를 대상으로 하였다. 사용한 올란자핀의 용량, 벤조디아제핀의 병용률, 탈락률과 탈락 사유, 자발적인 이상반응 보고, 생명징후, 실험실 검사 그리고 대부분의 부작용 척도 상에서 임상적으로 의미 있는 차이를 두 교체 방법간에 발견하지 못하였다. 다만 AIMS의 감소는 ’직접 교체 방법’군에서 보다 적었고, 항콜린제의 병용률은 ’시작-감량 교체 방법’군에서 보다 많았다. 기저 상태에서 전체 피험자의 SAS와 BARS 점수는 각각 3.5점과 1.8점이었으며 70% 이상의 피험자가 고프로락틴 혈증을 보였다. 올란자핀으로 교체한 후, SAS, BARS, AIMS 점수의 유의한 감소가 있었으며 고프로락틴 혈증을 보인 피험자 분율도 약 30%이하로 감소하였다. 그러나 교체 방법과 상관없이 올란자핀 교체 후 유의한 체중 증가가 있었다. 결론: 이 연구를 통해 교체 방법에 관계없이 비교적 안전하고 용이하게 올란자핀으로 교체 할 수 있음을 알 수 있었다. 그리고 기존 항정신병약물을 올란자핀으로 교체함으로써 일부 부작용들을 줄일 수 있음을 간접적으로 관찰할 수 있었다. 하지만 이 연구는 여러 제한점과 문제점을 지니고 있기 때문에 보다 체계적인 연구를 통해 검정이 필요하리라 생각된다. Objectives: This multicenter clinical trial involving 13 hospital sites compared the safely of switching to olanzapine between ’direct switching method’ and ’start-tapering switching method’. Method: This study included both inpatients and outpatients who fulfilled the criteria for schizophrenia as defined in the ICD-10, and were in need to be appropriate for switching antipsychotics. Subjects were randomly assigned to one of the two switching methods. For ’direct switching method’group, previous antipsychotics were abruptly discontinued and 10㎎ of olanzapine was administered, and previous antipsychotics was gradually tapered for 2 weeks. Olanzapine was used for 6 weeks and the dose was adjusted within the range of 5-20㎎. The safety of switching to olanzapine was measured with vital sings including body weight, adverse events reported spontaneously, laboratory tests, and various scales such as Simpson-Angus Scale(SAS), Barnes Akathisia Rating Scale(BARS). Abnormal Involuntary Movement Scale(AIMS), and Liverpool University Neuroleptic Side Effect Rating Scale(LUNSERS). Results: 103 patients were switched to olanzapine in this study. The comparison between two switching methods did not show any significant difference in the dosage of olanzapine used, the concomitant use of benzodiazepine, the rate and reasons of drop-out, the adverse events, vital signs, laboratory tests, and most scales for measuring side-effects. However, the decrease in AIMS scores was significantly lower in ’direct switching method’ group, and the concomitant use of anticholinergics was comparatively greater in ’start-tapering switching method’ group. At baseline, SAS and BARS scores were 3.5 and 1.8 points respectively, and more than 70% of the subjects showed hyperprolactinemia. After switching to olanzapine, SAS, BARS, and AIMS scores were significantly decreased and the proportion of the patients with hyperprolactinemia was also decreased to less than 30%. However significant weight gain after the treatment of olanzapine was observed regardless of switching method. Conclusion: This study may suggest that switching to olanzapine can be done with relatively high safety regardless of switching methods and olanzapine can significantly decrease some side-effects induced by other antipsychotics.

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.

지난 4년간 학회지 "신경정신의학" 심사 평가보고

오병훈,권준수,남궁기,김승현,지익성,김창윤,하규섭,박원명,김성곤,오강섭,김정범,이수정,정한용,이창욱,박용천,이영문,김세주,이병욱 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.5

Four Years Reports of "Journal of Korean Neuropsychiatric Association" during 2001 to 2005 were evaluated by 18 Editorial Board of Korean Neuropsychiatric Association. We investigated the articles to specific fields and rejection rate etc. by different section chiefs. Although several problems concerning review time duration and rejection guideline issues indicated but generally all reviewer processes proved relatively clear and concise criteria. Through these objective and systematic evaluation Processes, "Journal of Korean Neuropsychiatric Association" will develop a good journal.

상온 유동층에서 층내 수평전열관의 마모특성

한근희,김용철,류정인,선도원,민병무 한국화학공학회 2004 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.42 No.2

대부분의 유동층 연소장치에서 충물질과 비산된 입자에 의한 충내 전열관과 water wall의 전열관 표면의 마모는 계속적으로 골칫거리가 되고 있다. 본 연구는 단면적이 0.15m×0.30m인 상온유동층장치에서 마모하기 쉬운 아크릴 관을 사용하여 유동층에 파묻힌 전열관에 대하여 유동조건과 전열관의 배열효과에 대한 실험적인 연구를 나타냈다. 유동층의 단면적은 0.15m×0.30m이고 높이는 1.0m이다. 층물질은 강모래 평균입도 0.73, 1.24mm의 두 가지와, 평균입도 0.9mm의 무연탄 희재를 사용하였다. 유동층 높이는 0.45m이었다. 마모실험은 조건마다 100시간동안 유동화속도 1.2-1.8m/s 까지 변화시켜 수행하였다. 실험결과 마모율은 유동화속도가 증가할수록 증가하였고, 공기분배기로부터 떨어진 거리가 증가할수록 증가하였다. 그리고 공기분배기로부터 높이 0.6m의 비산영역에 위치한 전열관에 심한 마모를 나타냈다. 전열관의 원주방향에 대한 마모경향은 다른 부분과 비교하여 시계방향으로 4시 방향에서 8시 방향까지 심한 마모가 나타났고, 특히 5시 방향과 7시 방향은 심한 마모를 보였다. Erosion of in-bed tubes and water wall heat transfer surfaces by bed materials and elutriated particles have persistently plagued most fluidized bed combustion (FBC) systems. This papere presents a systematic experimental study of the effects of tube arrangement and flow condition on embedded tube erosion by using erosion-prone acrylic cylinders in a 0.15m×0.30m bench-scale cold fluidized bed. The bed material was two different sizes of river sand and anthracite ash with the average diameter of 0.73, 1.24, 0.90㎜, respectively. The static bed height was 0.45m. Erosion test was performed with the variation of fluidization velocity of 1.2 to 1.8m/s for 100 hours per set. The result shows that the erosion rate increased with fluidizing velocity, with distance from the distributor. The erosion was severe at the tube located in the splash zone of 60㎝ above the distributor. The trend with radial direction shows severe erosion at the 4-8 o'clock clockwise compare to other area, especially 5 and 7 o'clock clockwise.

폴록사머 188 및 멘톨에 의한 이부프로펜의 용해도 증가

용철순,정세현,박상만,이종달,최한곤 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.1

To enhance the solubility of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigate. In the absence and presence of additives such as ethanol and poloxamer 188, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by and abrupt decrease in solubility above the ratio of 4:6, indicating tat 4 parts of ibuprofen formed eutetic mixture with 6 parts of menthol. In the presence of poloxamer, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen . Furthermore, in the presence of poloxamer, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The solution with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2㎎/ml. Thus, menthol gave the greatly enhanced solubility of ibuprofen with poloxamer 188.

폴록사머를 이용한 디클로페낙 고형 좌제의 개발

용철순,오유경,김정애,김용일,박상만,양준호,이종달,최한곤 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.2

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting points of various formulations composed of P 124 and P 188 were investigated. To investigate the effect of poloxamer to the dissolution and dissolution mechanism of diclofenac sodium from the suppository the dissolution of diclofenac sodium delivered by the poloxamer-based suppository was performed. Furthermore, to investigate the mucoadhesive property of the poloxamer-based solid suppository, the identification test in the rectum was carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous. Very small amounts of P 188 affected the melting points of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about 32℃ was a solid form at room temperature and instantly melted at physiological temperature. Furthermore, very small amounts of P 188 in the poloxamer-based suppository hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. At 4 h after administration, the blue color of poloxamer-based suppository [diclofenac sodium/poloxamer mixture (2.5/97.5%)] with the P 124/P 188 ratio of (97/3%) and blue lake in the rectum was faded. However, the position of suppository in the rectum did not significantly change with time. Thus, it retained in the rectum for at least 4 h. Our results indicated that the poloxamer-based solid suppository with P 124 and P 188 would be a candidate of rectal dosage from for diclofenac sodium.

산화아연계 무기질과 솔잎추출물 첨가에 의한 농산물 포장 필름의 광 및 미생물 열화능 개선

한신,나현정,강용구,박찬영 전남대학교 촉매연구소 2001 觸媒硏究 論文集 Vol.22 No.-

To invent environmentally friendly materials for packaging of agricultural produce, morphological and mechanical properly changes after daylight exposure and soil deposit for LDPE films composed of different incorporation substances have been investigated. Silver coated ceramic, zinc oxide, fine particle of ferrofluid and pine needle's extract were the incorporated substances. The pine needle's film degrades fast in soil while the silver coated ceramic's film shows daylight decay more on the morphological view. The mechanical strength keeps almost same. But turndown of elongation is explicit on the pine needle's film and silver coated ceramic's film.

RAPD와 핵 리보솜 DNA ITS2 염기서열에 의한 한국산 전나무속 식물의 유전적 변이 및 계통유전학적 분석

정용환,한상현,오유성,고미희,고석찬,김문홍,오문유 濟州大學校 基礎科學硏究所 2001 基礎科學硏究 Vol.14 No.2

We analyzed the genetic variation and phylogenetic relationship among fourteen taxa of GenusAbies distributed in Korea using random amplified polymorphic DNA (RAPD) and internal transcribed spacer (ITS) 2 sequences of the nuclear ribosomal DNA (rDNA). RAPDs were used for identification of selected taxa by amplification using single 10-mer primers of arbitrary sequence. Fourteen taxa were clearly classified with 10 arbitrary primers, which generated 102 useful polymorphic bands that were evaluated according to the presence or absence of the fragments of equal size. The genetic distance between A. koreana for. chlorocarpa and A. koreana for. rubrocarpa was 0.127, showing the closest among any other pairs. By comparing the base sequences in the ITS2 region of the nuclear rDNA, genetic relationship was assesed among selected taxa. It showed twenty six sites of point mutation (base substitution) in 243 base pairs (bp) of ITS2 region. The G+C contents of ITS2 region were ranged from 58.3% to 61.7%. The value of nucleotide divergence among selected taxa was ranged from 0.4% to 9.8%. These results showed that RAPD and ITS2 sequence analysis was a useful tool for elucidating phylogenetic relationship and selection of specific marker in Abies species.

Disel 機關의 渦給性能에 關한 硏究

韓龍雲,金重燁,權純益 嶺南大學校 工業技術硏究所 1981 연구보고 Vol.9 No.2

The factors that effect the power output of diesel engine are intake temperature, intake pressure, compression ratio and so on, in constant revolution. Intake pressure and compression ratio of them are much more effective. If the compression ratio is raised, the thermal efficiency of engine increases, but silent driving is difficult for maximum combustion pressure. The durability of engine decreases also for vibration and mechanical strain of materials, and the weight of engine per horse power increases. In this paper an intake pressure in charge of negative effects to lower compression ratio is raised. The compression ratio is decreased through the gasket is replaced by thick copper plate between cylinder and cylinder head. The effect of supercharge is evaluated experimentally from measuring of an engine power output, fuel consumption, and intake air volume. As a result of a decreased compression ratio, it becomes the same as natural aspiration before change compression ratio to increase about 3% to supercharging-pressure change ratio per unit compression ratio in mean effective pressure. And it becomes also the same as natural aspiration before change compression ratio to the increase of supercharging pressure about 1.8% in thermal efficiency. In case the supercharging pressure is much greater than the former to increase intake air pressure, it will give better effects to lower compression ratio than higher compression ratio with natural aspiration.

정신과 입원환자의 정신사회적 스트레스 요인에 관한 연구

한선호,권영준,정한용 大韓神經精神醫學會 1989 신경정신의학 Vol.28 No.6

The psychosocial stressors experienced in the 6 months prior to the admission were studied in 249(140 male and 109 female) psychiatric inpatients who were hospitalized in the Neuropsychiatric department of Soonchunhyang University Hospital from January 1987 to December 1988. The results were as follows : 1) Among the 249 cases, 120(48.2%) cases had the psychosocial stressors prior to admission. 2) 37.9% of male cases and 61.5% of female cases had the psychosocial stressors prior to admission. Female cases had significantly higher occurrence of the psychosocial stressors. 3) By the educational level, there was a significant difference in occurrence of psychosocial stressors prior to admission. Middle school graduates had the highest, no education had the lowest occurrence of the psychosocial stressors. 4) By the occupation, there was a significant difference in occurrence of the psychosocial stressors prior to admission. Housewives had the highest, unemployed had the lowest occurrence of the psychosocial stressors. 5) 90.0% of the cases with adjustment disorder, 81.9% of the cases with anxious disorders, 66.7% of the cases with depressive disorders. 66.7% of the cases with somatoform disorders, 60.0% of the cases with paranoid disorders, 58.1% of the cases with bipolar disorders, 56.1% of the cases with psychotic disorders not elsewhere classified, 27.8% of the cases with organic mental disorders, 27.5% of the cases with schizophrenic disorders, 15.4% of the cases with personality disorders, and 8.3% of the cases with substance use disorders had the psychosocial stressors prior to admission. When cases were grouped into neurosis and psychosis, there was no significant difference between two groups in occurrence of the psychosocial stressors. 6) Major psychosocial stressors with theirs frequency were occupational problems(21.7%), physical illness or injury(20.0%), other interpersonal problems(18.3%), and conjugal problems(16.7%).