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.

뇌종양의 악성도 판정을 위한 분열기 세포측정에 관한 연구

한용표,변진수,허철,홍순기,김헌주,조미연,정순희,김호근 대한신경외과학회 1992 Journal of Korean neurosurgical society Vol.21 No.11

Tissue markers of cellular proliferation have been utilized as prognostic indicators in tumors of the central nervous system. Nucleolar organizer regions represent transcriptionally active sites of ribosomal deoxyribonucleic acid and can be identified by a simple argyrophilic technique. The authors describe a standardized approach to the assessment of these argyrophilic nucleolar organizer regions(AgNORs) in 25 astrocytomas(including 6 glioblastomas), 6 oligodendrogliomas and 1 xanthochromic astrocytoma, which were also estimated in association with 2-year survival post-operatively. Appropriate sections were silver stained and AgNORs were counted in 1000 cells. In cases of astrocytoma, the mean AgNORs/cell count of group survived more than 2 years after operation was significantly different from that survived less than 2 years : 1.93±1.13 vs. ≥ 4.79±3.90. And the mean AgNORs/cell count was 1.53±0.32 in low grade astrocytoma. 2.03±0.59 in grade Ⅲ astrocytoma, and ≥6.64±3.77 in grade Ⅳ astrocytoma. Among the patients with the same grade astrocytoma, the mean AgNORs/cell count was lower in the cases of long survival rather than short survival. The assessment of AgNORs can be easily performed by any surgical pathology laboratory without specialized equipment. It may be used as a valuable and independent prognosticator of biological behavior in cases of astrocytoma.

프레탈정 (실로스타졸 100mg)에 대한 실로스탄정 (한국유나이티드 제약)의 생물학적 동등성

용철순,이경희,최진석,박병주,정세현,김용일,박상만,유봉규,이종달,최한곤 한국병원약사회 2003 병원약사회지 Vol.20 No.2

Bioequivalence of one cilostazol tablets, the Pletaal^(R)(Korea Otsuka Pharmaceutical Co., Ltd.) and Cilostan^(R)(Korea united Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Sixteen normal male volunteers(age 20~30 years old)were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 100㎎ of cilostazol were orally administered, blood was taken at predetermined time intervals and the concentration of cilostazol in plasma was determined with an HPLC method using UV detector. The pharmacokinetic parameters(C_(max), T_(max) and AUC_(t)) were calculated and ANOVA was utilized for the statistical analysis of parameter. The results showed that the differences in C_(max), T_(max) and AUC_(t) between one tablet were 16.08%, 18.88% and 17.57%, respectively. The powers (1-β) for C_(max), T_(max) and AUC_(t) were 85.03%, 83.92% and 80.12%, respectively. Detectable differences(Δ) and confidence intervals were all less than 20%, and confidence interval of all the parameters were also less than 20% at the significance level(α) of 0.05. All of these parameters met the criteria of KFDA for bioequivalence, indicating that Cilostan^(R) tablet is bioequivalent to Pletaal^(R) tablet.

헬리코박터 파이로리 균 진단용 ^13C-요소 캅셀의 개발

용철순,김용일,김지만,강성훈,권기철,이종달,김종국,사홍기,최한곤 영남대학교 약품개발연구소 2002 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

The purpose of this study was to develop a new ^13C-urea-containing capsule for diagnosis of H.pylori. The urea-containing capsules were prepared with various diluents such as polyethylene glycol (PEG), microcrystaline cellulose, sodium lauryl sulfate and citric acid. The dissolution test, ^13C-urea breath test and stability test were then performed on the capsules. Microcrystalline cellulose and sodium lauryl sulfate retarded the initial dissolution rates of urea. However, PEG increased the initial dissolution rates of urea. Furthermore, two formulae composed of PEG,[^13C-urea/PEG (38/1.9 mg/cap)] and [^13C-urea/PEG (38/1.9/1.9 mg/cap)] had the maximum DOB value. about 16 at 20 min, while the formula composed of only 38 mg ^13C-urea had the maximum DOB value at 30 min. The results indicated that PEG improved the sensitivity of ^13C-urea in the human volunteers. The capsule [^13C-urea/PEG (38/1.9 mg/cap)] was stable for at least six months in 25 and 37℃. Thus, a PEG-containing capsule, [^13C-urea/PEG (38/1.9 mg/cap)] would be a more economical, sensitive and stable perparation for diagnosis of H. pylori.

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.

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.

소형엔진의 배출가스측정방법에 따른 질소산화물 및 매연에 관한 연구

한영출,나완용,오용석,문병철,박봉규,박귀열 한국공작기계학회 2001 한국생산제조학회지 Vol.10 No.3

Recently, increasing usage of diesel vehicle, many countries try to reduce the pollutant materials by emission regulation standard. Particularly, in our country, the supplement ratio of diesel vehicle is high, and air pollution by vehicle exhaust gas is very serious. So, in study, we tested exhaust gas by various mode in light duty diesel engine. Therefore, we can know about NOx and smoke seriousness.

헬리코박터 파이로리 균 진단용 ^13C-요소 캅셀의 개발

용철순,김용일,김지만,강성훈,권기철,이종달,김종국,사홍기,최한곤 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.1

The purpose of this study was to develop a new ^13C-urea- containing capsule for diagnosis of H. pylori. The urea-containing capsules were prepared with various diluents such as polyethylene glycol (PEG), microcrystalline cellulose, sodium lauryl sulfate and citric acid. The dissolution test, ^13C-urea breath test and stability test were then performed on the capsules. Microcrystalline cellulose and sodium lauryl sulfate retarded the initial dissolution rates of urea. However, PEG increased the initial dissolution rates of urea. Furthermore, two formulae composed of PEG, [^13C-urea/PEG (38/1.9 mg/cap)] and [^13C-urea/PEG/citric acid (38/1.9/1.9 mg/cap)] had the maximum DOB value, about 16 at 20 mim, while the formula composed of only 38 mg ^13C-urea had the maximum DOB value at 30 min. The results indicated that PEG improved the sensitivity of ^13C-urea in the human volunteers. The capsule [^13C-urea/PEG (38/1.9 mg/cap)] was stable for at least six months in 25 and 37℃. Thus, a PEG-containing capsule, [^13C-urea/PEG (38/1.9 mg/cap)] would be a more economical, sensitive and stable preparation for diagnosis of H. pylori.

경피흡수에 영향을 미치는 인자

용철순,이종달,최한곤 영남대학교 약품개발연구소 2000 영남대학교 약품개발연구소 연구업적집 Vol.10 No.-

Transdermal drug delivey systems(TDDS) are known to have various adavantages over conventional dosage forms, such as simple dosage, prolonged and controlled action of drugs, avoidance of hepatic first-pass effect, and greater improved patient compliance. One of the main shortcomings of TDDS, however, is poor percutaneous absorption. Many biological and physicochemical factors influencing percutaneous absorption is described together with the corresponding experimental results and practical examples.

아세클로페낙 연질캡슬(클란자 에스 연질캡슬)의 개발

용철순,이경희,최진석,박병주,정세현,김용일,박상만,배명수,김귀자,김영식,유창훈,강성룡,유봉규,이종달,최한곤 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.1

To develop and aceclofenac soft capsule, four preparations with various solubilizers were prepared and their dissolution test was carried out. Among four preparations tested, a preparation with ethanolamine was selected a formula of aceclofenac soft capsule (Clanza S^(™), since it showed the fastest dissolution rate. Bioequivalence of aceclofenac tablet, Airtal^(™)(Dae-Woong Pharmaceutical Co., Ltd.) and aceclofenac soft capsule, Clanza S^(™)(Korea United Pharmaceutical Co., Ltd.) was evaluated according to the guideline of KFDA. Fourteen normal male volunteers (age 20-25 years old) were divided into two groups and a randomized 2×2 cross-over study was employed. After oral administration of one tablet or capsule containing 100 ㎎ of aceclofenac, blood ws taken at predetermined time intervals and the concentration of aceclofenac in plasma wa determined with an HPLC method under UV detector. The pharmacokinetic parameters (C_(max), T_(max) and AUC_(t)) were calculated and ANOVA was utilized for the statistical analysis of parameters using logarithmically transformed AUC_(t), C_(max) and T_(max) between Airtal tablet and Clanza soft capsule were 2.89%, 0.18% and 43.0%, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.250(e.g.log(0.81) - log(1.23) and log(0.89) - log(1.14)) for AUC_(t) and C_(max), respectively. Thus, the criteria of the KDFA guidelines for the equivalence was satisfied, indicating that Clanza S^(™) soft capsule is bioequivalent to Airtal^(™) tablet.