클렌부테롤 경피흡수제제의 개발

최한곤,권기철,정시영,이종달,용철순 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

The advantages of transdermal administration are avoiding hepatic first pass effect, minimizing inter- and intra-patient variation, maintaining steady-state plasma level to provide long-term therapy from a single dose, and allowing a rapid termination of drug input. Clenbuterol, a selective B_(2)-adrenergic receptor stimulant, has been introduced as a polent bronchodilator for patients with bronchial asthma, asthma, chronic obstructive bronchial disease. For the development of transdennal systems containing clenbuterol, two limiting factors ? long lag time and low flux - must be overcome. In this studym we altempted to select optimal formulation for preparation of clenbuterol patch using hairless mouse skin and flow-through diffusion cell. The flux of clenbuterol increased as the percent of clenbuterol dose dependently in the concentration range of 5-15%. Based on this result, we fixed the concentration of clenbuterol as 15%. The effect of various penetration enhancers on percutaneous absorption of clenbuterol through hairless mouse skin was investigated. Labrafil was the most effective enhancer, which increased the permeability of clenbuterol approximately 4-fold compared with the control without penetration enhancer. Optimal enhancer concentration was 3%. The effect of various adhesives on penetration of elenbuterol was also investigated. Among the adhesives studied, MA-31 was the most effective adhesive. Futhermore, the clenbuterol patch composed of 15% clenbuterol. 3% Labrafil and 82% MA-31, which gave most excellent penetration of drug in in vitro penetration study, maintained therapeutic plasma levelsin in vivo study using S.D. rats. These studies demonstrated a good feasibility of clenbuterol administration through the intact skin using a transdermal patch, and show a possibility of the development of clenbuterol patches.

천마 성분인 4-히드록시-메톡시벤즈알데히드 및 파라-히드록시벤즈알데히드의 흰쥐에서의 약물동태

용철순,권기철,김정애,하정희,이동웅,허근 영남대학교 약품개발연구소 1999 영남대학교 약품개발연구소 연구업적집 Vol.9 No.-

Gastrodia elata (GE) is an oriental medicinal herb which has been used traditionally for the treatment of var-ious brain diseases including convulsion and epilepsy. The purpose of this study was to determine pharmacokinetic param-eters of 4-hydroxy-3-methoxybenzaldehyde (HMBA) and p-hydroxybenzaldehyde (PHBA), constituents of GE, in rats. Male rats were cannulated in the femoral vein, femoral artery, bile duct and ureter. They received a single i.v. bolus dose of either HMBA or PHBA through the femoral vein. The concentration of HMBA or PHBA in plasma, bile and urine sam-ples were analyzed by reversed-phase HPLC. HMBA and PHBA have very short half-lives, i.e. 4.03 and 2.26 minutes respectively. Most of HMBA and PHBA were thought to be eliminated through metabolism as the metabolized fraction approaches unity. Derivatives of HMBA or PHBA with longer biological half-lives should be designed to develop better anticonvulsants and more complete qualitative and quantitative understanding of the overall pharmacokinetic fate of these compounds awaits further investigation.

프로스타글란딘 E₁ 요도좌제의 제조 및 평가

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

The purpose of this work is to develop a transurethral suppository containing prostaglandin E₁(PGE₁), which stabilizes the drug, gives no irritation to physiological body and enhances the erectile response of PGE₁. PGE₁ transurethral suppositories were prepared with various amounts of compositions such as saturated polyglycolysed glyceride(Suppocire^(?) AP, SAP), polyoxyethylene hydrogenated castor oil (HCO-50) and ethanol. The melting points, viscosities and PGE₁ release of the suppositories were investigated. Ocular irritation test was carried out after application of PGE₁ suppository to rabbit's eye. The intracavemous pressure(ICP), penile length and duration of erectile response were determined after transurethral administration of PGE₁ suppository and compared with those after intracavemosal injection of PGE₁ solution to cats. HCO-50 hardly affected the melting points and viscosities of PGE₁ suppositories. Additionally, PGE₁ transurethral suppositories, whose melting point ranges was 34-35℃, was speedily melted in physiological body. HCO-50 significantly decreased the dissolution rates of PGE₁ from the suppositories. Dissolution mechanism analysis showed the release of PGE₁ was pro-portional to the square root of time, indicating that PGE₁ might be released from the suppositories by Fickian diffusion. The release rate of PGE₁ from PGE₁ suppository [PGE₁/SAP/HCO-50/ethanol (1/94.5/2.5/2%)] was about 80% within 2h. This PGE₁ suppository gave no irritation to the urethral tissue less sensive than ocular tissue. Furthermore, PGE₁ in this suppository was stable at 4℃ for 2 years. This suppository increased the ICP and penile erection similar to those of injuctable PGE₁ solution. However, it gave 2.5-fold increased dura-tion of erectile response than injectable PGE₁ solution. Our results suggested that it gave more effective erectile response than injectable PGE₁ solution in cats. It is concluded that this PGE₁ suppository with good safety, excellent stability and enhanced erectile response, could be a more effective and convenient transurethal delivery system of PGE₁.

지방산, 지방 알코올 및 프로필렌글리콜이 클렌부테롤의 경피투과에 미치는 영향

이영대,권기철,정시영,이종달,용철순 영남대학교 약품개발연구소 2000 영남대학교 약품개발연구소 연구업적집 Vol.10 No.-

Clenbuterol, a selective β_(2)-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic bronchitis and pulmonary emphysema. For the purpose of developing a transdermal preparation for clenbuterol, we attempted to select an optimal solvent system and permeation enhancer among fatty acids and fatty alcohols which are known to accelerate the penetration of various drugs in permeation experiments using hairless mouse skin and Franz diffusion cell. Apparent partition coefficient of clenbuterol was increased as pH of buffer solution was increased and solubility of clenbuterol was increased as the percent of propylene glycol(PG) in buffer solution(pH10) was increased. Permeability of clenbuterol from different buffer(pH 10)/PG solvent mixtures was decreased as the percent of PG in pH 10 buffer solution was increased and among the various enhancers studied, lauryl alcohol was found to be the most effective enhancer, increasing the permeability of clenbuterol approximately 76-fold compared with control. Lauryl alcobol(0-2%) enhanced the permeability of clenbuterol concentration-dependently. In this study, the optimal solvent system for the penetration of clenbuterol was found to be 50/50 buffer(pH 10)/PG solvent mixture containing 2% lauryl alcohol.

프레탈^(R)정(실로스타졸 50mg)에 대한 실로졸^(R)정의 생물학적 동등성

최한곤,권기철,이승호,김학미,박병주,유봉규,이종달,이경희,하정희,우종수,박인숙,최진석,용철순 한국병원약사회 2003 병원약사회지 Vol.20 No.1

Bioequivalence of two cilostazol tablets, the Pletaal^(R)(Korea Otsuka Pharmaceutical Co., Ltd.) and the Cilozol^(R)(Hanmi Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA, Sixteen normal male volunteers(age 20~29 years old) were divided into two groups and a randomized 22 cross-over study was employed. After two tablets containing 50㎎ 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 parameters. The results showed that the differences in C_(max), T_(max) and AUC_(t) between two tablets were 4.99%, 1.74% and 7.68%, respectively. The powers(1-β) for C_(max), T_(max) and AUC_(t) were83.92%, 80.12% and 85.03%, 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 Cilozol^(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.

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.

Thick Soil River

Qi ZHE 한국색채학회 2015 International Invitation Exhibition of Color Works Vol.2015 No.-

Impression of Jinan

Qi Yu Zhe,Kim, Kie Su 한국콘텐츠학회 2022 ICCC International Digital Design Invitation Exhib Vol.2022 No.12

Evaluation of Retinal Nerve Fiber Layer Thickness and Optic Nerve Head Parameters in Obstructive Sleep Apnoea Patients

Qi Zhe Ngoo,Nazihatul Fikriah A,Baharudin A,Wan Hazabbah WH 대한안과학회 2021 Korean Journal of Ophthalmology Vol.35 No.3

Purpose: To study the retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters in obstructive sleep apnoea (OSA) patients and their relationship with severity of the disease. Methods: A cross-sectional, hospital-based study. Fifty-four OSA subjects and 54 controls were recruited. Candidate that fulfil the criteria with normal ocular examinations then proceed with spectrum domain Cirrus optical coherence tomography examinations. ONH parameters and RNFL thickness were evaluated. Apnoea-hypopnoea index (AHI) of the OSA group were obtained from the medical record. Results: In OSA, mean of average RNFL thickness was 93.87 μm, standard deviation (SD) = 9.17, p = 0.008 (p < 0.05) while superior RNFL thickness was 113.59 μm, SD = 16.29, p ≤ 0.001 (p < 0.05). RNFL thickness fairly correlate with severity of the disease (AHI), superior RNFL with R = 0.293, R2 = 0.087, p = 0.030 (p < 0.05), and nasal RNFL R = 0.292, R2 = 0.085, p = 0.032. No significant difference and correlation observed on ONH parameters. In control group, mean of average RNFL thickness was 98.96 μm, SD = 10.50, p = 0.008 (p < 0.05) while superior RNFL thickness was 125.76 μm, SD = 14.93, p ≤ 0.001 (p < 0.05). Conclusions: The mean of the average and superior RNFL thickness were significantly lower in the OSA group compare to control. Regression analysis showed RNFL thickness having significantly linear relationship with the AHI, specifically involving the superior and nasal quadrant.