다시마 식이가 흰쥐에서 글리피지드의 체내동태에 미치는 영향

최한곤,장보현,이종달,유봉규,용철순 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.2

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alternations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increase risk of micovascular, macrovascurlar, and neuropathic complications. However, the precise mechanixm of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. The purpose of this study was to investigate the effect of Laminaria japonica diet on the absorption, distribution, metabolism and excretion of glipizide which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agents were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as k_a, t_1/2, C_max, t_max, and AUC. Administration of glipzide in normal rats treated with Laminaria japonica diet showed significant increase in AUC, k_a, t_1/2, t_max and decrease in C_max, compared to those without Laminaria japonica diet. This might result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption. Administration of glipizide in diabetic rats treated with Laminaria japonica diet showed significant increase in t_1/2 and t_max, and decrease in C_max, compared to those without Laminaria japonica diet. This might also result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption and flattened blood concentration of glipizide. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of glipizide caused by long-term Laminaria japonica diet.

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.

흰쥐에서 다시마 식이가 메트폴민의 체내동태 및 당 흡수에 미치는 영향

최한곤,장보현,이종달,김정애,유봉규,용철순 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.3

Drug interactions with food, on occasion, led to serious nutritional and functional changes in the body as well as alterations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of microvascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remins unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo-or hyperglycemia and preventing complications. Laminaria japonica is a brown macroalgae which can be used as a functional diet due to high content of diatery fiber. the purpose of this study was to investigate the effect of Laminaria japonica diet on the pharmacokinetics of metformin which are frequently used in the treatment of diabetes. Diabetic rats induced by strep-tozotocin were employed in this study. Blood concentrations of oral hypoglycemic agent, metformin, were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as k_(a), t_(1/2), C_(max), t_(max), and AUC, C_(max), and k_(a), and increase in t_(max), compared to those with normal diet. This oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of metformin caused by ong-term Laminaria japonica diet.

클렌부테롤의 피부투과에 미치는 경피흡수촉진제의 영향

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

Clenbuterol, a selective β_2-adrenergic receptor stimulant, has been introduced as a potent bronchodilator for patients with bronchial asthma, chronic obstructive bronchial disease, chronic bronchitis and pulmonary emphysema. The percutaneous permeation of clenbuterol was investigate in hairless mouse skin after application of 50/50 buffer(pH 10)/propylene glycol solvent mixture. The enhancing effects of various penetration enhancers such as terpenes, non-ionic surfactants, pyrrolidones, fatty acids and some other enhancers on the permeation of clenbuterol were evaluated using Franz diffusion cell. Among terpenes studied, 1,8-cineole was the most effective enhancer, which increase the permeability of clenbuterol approximately 39.33-fold compared with the control without penetration enhancer, followed by menthone with enhancement ratio of 23.57. Nonionic surfactants did not have significant enhancing effects. N-Lauryl-2-pyrrolidone increased the permeability of clenbuterol approximately 4.51-fold compared with the control. Lauric acid increased the permeability of clenbuterol approximately 35.57-fold with decreasing the lag time from 2.64 to 0.52 hr. Oleic acid, linoleic acid, the permeability of clenbuterol 9.24-fold compared with that without enhancer.

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.

플라즈마 이온주입기에서의 시변환 쉬스 연구

김곤호,김건우,김영우,최영도,김종식,김상진,한승희,홍문표 漢陽大學校 工學技術硏究所 1998 工學技術論文集 Vol.7 No.1

Abstract- In a plasma source ion implantation, the target is successively biased by negative voltage pulses with an intrinsic finite rise time, resulting in the time-dependent sheath formation around the target. Measurement of time-dependent sheath during the pulse rise show the ion matrix sheath development which is in proportion to square root of time and pulse rise rate over plasma density but independent of the ion mass.

X-관련성 만성육아종성질환의 진단을 위한 PMA-activated NBT 검사

김중곤,조한익,오흥범,김의종,최강원 대한감염학회 1996 감염 Vol.28 No.1

목적 : Activated NBT 검사는 만성육아종성질환을 선별하는 검사이다. 활성제로 PMA를 사용하면 X-linked CGD의 경우 보인자를 감별할 수 있다. 방법 : CGD의 가족력을 부인하는 정상인 30명을 대상으로 PMA activated NBT 슬라이드 검사를 실시하여, 정상대조에서의 formazan 형성율을 보았으며, 동일 검사를 CGD가 강력히 의심되는 환자와 그 가족에 대하여 실시하였다. 결과 : 정상대조 30명 전원에서 98% 이상의 formazan 형성세포가 관찰되었다. 환자에게 실시한 결과 세환자 모두에서 0%의 결과를 보였다. 환자의 어머니에서는 각각 57, 70, 67%의 결과를 보였다. 결론 : 본 연구를 통하여 세 환자는 X-관련성 만성육아종성질환이라는 진단을 내릴 수 있었다. PMA activated NBT 슬라이드 검사는 시행하기가 쉽고 재현성이 좋으므로, 어러 검사실에서 소아기 면역결핍증을 선별하는 검사의 하나로 시행되는게 바람직하다고 사료된다. Background : Chronic granulomatous disease(CGD) is uncommon inherited disorder in which phagocytic cells fail to produce antimicrobial superoxide(O₂) due to NADPH oxidase deficiency. This disease can be easily screened by activated nitroblue tetrazolium(NBT) test. In case of X-linked CGD, carriers also can be detected. Methods : PMA(phorbol myristate acetate) activated NBT test was performed as previously described. Test performance was evaluated in 30 normal persons who denied family history mimicking CGD. Test was also applied to the three strongly suspected cases of CGD. Two of the cases were 12 year old boy and 7 year old boy, who suffered from many infectious diseases since 6 month old and 4 month old, respectively. The other remaining case was 22 year old man who suffered from many infectious diseases since 6 year old, but now relatively in health compared to the other two cases. Results : More than 98% formazan formation was observed in all normal controls. No formazan positive cell was shown in all of the three patients. However, applied to the mothers, the test revealed 57%, 70%, 67% positive cells, respectively. Conclusion:X-linked transmission of CGD could be determined with the results of PMA activated NBT slide test. This test can be easily performed. It would be better to do this test routinely as one of the tests for the screening of the immmunodeficiency syndrome in childhood.

홍삼 엑기스를 함유한 분말주의 제조 및 평가

이사원,최한곤,박정일,김종국 영남대학교 약품개발연구소 2000 영남대학교 약품개발연구소 연구업적집 Vol.10 No.-

To develop a dry alcohol containing red ginseng extract, dry alcohols composed of ethanol, water, dextrin and sodium lauryl sulfate were prepared using spray dryer, and their ethanol contents and encapsulation efficiencies were deter-mined. An optimal dry alcohol containing red ginseng extract was chosen and the feeling for its oral administration was eval-uated. Dextrin at dextrin/water weight ratios below 1.6/1 and ethanol at ethanol/water weight ratios below 1/1 remarkably increased both the ethanol contents and encapsulation efficiencies of dry alcohols. However, dextrin at dextrin/ water weight ratios above 1.6/1 and ethanol at ethanol/water weight ratio above 1/1 slightly decreased the both parameters. It might be due to the low solubility of dextrin in ethanol and limited diffusion coefficient of ethanol to the dextrin shell. Furthermore, 0.5%(w/w) sodium lauryl sulfate gave the maximum ethanol content of dry alcohol. The more increased amounts of red ginseng extract were added, the more increased amounts of ginsenoside Rb1 but the more decreased amounts of ethanol were encap-sulated in dry alcohols. A dry alcohol containing red ginseng extract was prepared with dextrin/ethanol/water(1/1/1, w/w/w) mixed solution, in which 0.5%(w/w) sodium lauryl sulfate and 20%(w/w) red ginseng extract were dissolved. It contained the ethanol contents of 31.17±1.33%(w/w) and ginsengoside Rb1 of 243.0±7.0㎍/g. It gave the moderate taste of red ginseng extract at its oral administration with or without water. Thus, the dry alcohol containing red ginseng extract can be further developed as a more convenient dosage form for red ginseng extract.

作業環境 騷音에 對한 考察

김남천,최한영,채수권,손정곤 서울保健大學 1991 論文集 Vol.11 No.1

A Review was performed on occupational noise exposure as follows ; First, Domestic laws and ordinances relative to occupational noise are surveyed, and also a legal action which both employor and employer can be taken to prevent a exposure noise are showed. Second in order to evaluace of occupational noise problems, various noise standards and method have compared with some overseas countries.

유산균을 이용한 경구용 항원 단백질 수송능 연구

조희정,최한곤,김정애,오유경 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2

A promising application of Lactococcus lactis is its use as live vehicles for production and delivery of heterologous proteins of vaccines and therapeutic substances. Because L. lactis has GRAS ("generally regarded as safe") status, use tested whether L. lactis could function as the carrier of the L1 protein of human papillomavirus (HPV) type 16. The RNA level expression of L1 gene was detected in L. Laois. The L1 protein was expressed in L. luctis with LI gene. The growth of strains L. lactis with an empty plasmid (pAMJ328) and L. lactis with L1-encoding plasmid (pAMJ328-L1) was slightly decreased in comparison with the growth of strains L. lactis (wild type). However, all the three strains of L lactis maintained the ability to ferment sugars primarily into lactic acid, indicating that L1 protein did not affect the biochemical property of L.. lactis. These results suggest that L. lactis. capable of carrying LI protein, might he further developed as a biocompatible oral protein delivery system.