複合 韓藥劑 淸籬滋坎湯의 抗癌效果 및 作用機轉 糾明

Cho, Kyung-Sam,Kim, Si-Young,Park, Jai-Kyung,Choi, Seung-Hoon,Chung, Se-Young,Yoon, Hwi-Joong 경희대학교 동서의학연구소 1999 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.1999 No.1

Kyung Sam Cho¹Si Young Kim¹, Jai Kyung Park²,Seung Hoon Choi³,Se Young Chung⁴, Hwi Joong Yoon¹¹College of Medicine, ²East-West Medical Research Institute, ³College of Oriental Medicine, ⁴College of Pharmacology, Kyung Hee University,Seoul, Korea. The Anti-cancer Effect of Oriental Medicine Chung-Ri-Ja-Gam-Tang in the Mouse with Metastatic Lung Cancer. Proceedings of International Symposium on East-West Medicine, Seoul. 231-243, 1999.-The oriental medicine Chung-Ri-Ja-Gam-Tang is an herbal medicine which has been used for pulmonary diseases and known as having immune stimulatory effects. It has been known effective in lung cancer. So we studied the effects and the mechanisms of this herbal medicine it the mouse with metastatic lung cancer. The metastatic lung cancer of the mouse was produced with melnoma cell line(B16BL/6).5×10□/mouse tumor cells were injected intravenously to the CDF1 mouse via tail vein. The mice were divided 4 groups. The first group was treated with 50mg/kg extract of Chung-Ri-Ja-Gam-Tang per oral for 10 days after cancer cell injection, second group treated with saline after cancer cell injection, the third group with medicine without cancer cell, and the last group with saline only. After 10 days treatments some of the mice were scarificed and the lung and spleen was removed. The survival duration, weight change, the number of metastatic cancer nodule of the lung, the NK cell activity, the capacity of cytokines(INF-γ,INF-α,IL-2) production and the proliferation activities of mouse lymphocytes were measured. The surival times of the group 1 mice were longer and the weight loss was less than the group 2 significantly. The number of the metastatic nodule of the lung were decresed in the group 1 than the group 2. The production of INF-γ,was increase in group 2 than group 3 and 4, IL-2 production was increased in group 1 than group 2,3,4 significantly. There was no difference in TNF- α production and proliferation activity of lymphocyte in each group. The NK cell activity was significantly increased in group 1 than group 2,3,4. We conclude that the Chung-Ri-Ja-Gam-Tang has the effect of increasing the NK cell activity of the CDF1 mouse with metastatic lung cancer(B16BL/6). And it is suggested that the increased production of the IL-2 is the mechanisms of enhanced NK cell activity.

니세틸 정(아세틸-엘-카르니틴 500 mg)에 대한 엘카틴 정의 생물학적 동등성

조혜영,윤지훈,오인준,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Acetyl-L-camitine (ALC), an endogenous component of the L-carnitine family, is a naturally existing molecule synthesized from L-carnitine (LC) by carmtine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, Nicetile^TM (Dong-A Pharmaceutical Co.) and L-Cartin^TM (Kuhn Il Pharmaceutical Co.), according to the guidelines of Korea Food and Drug Administration (KFDA). The ALC release from the two ALC tablets in vitro was tested using KP Ⅶ Apparatus Ⅱ method in various dissolution media (pH 1.2, 6.0 and 6.8). Twenty six normal male volunteers, 24.46±3.67 years in age and 64.45±5.54 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 500㎎ of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. The dissolution profiles of the two ALC tablets were similar in all the dissolution media. The pharmacokinetic parameters such as AUC_t, C_max and T_max were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC_t, C_max and T_max between two tablets were 0.35%, 0.93% and 2.34%, respectively, when calculated against the Nicetile^TM tablet. The powers (1-β) for AUC_t and C_max were 98.72% and 85.48%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 13.21% and 18.42% for AUC_t and C_max, respectively). The 90% confidence intervals were within ±20% (e.g., -7.38~8.09 and -9.86~11.72 for AUC_t and C_max, respectively). These two parameters met the criteria of KFDA for bioequivalence, indicating that L-Cartin^TM tablet is bioequivalent to Nicetile^TM tablet.

아젭틴 정(염산아젤라스틴 1 mg)에 대한 아젤라 정의 생물학적 동등성

조혜영,윤지훈,서유리,오인준,이성관,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Azelastine, a phthalazinone derivative, is an antiallergic agent which demonstrates histamine H_1-receptor antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Thus, azelastine may be useful in the management of both asthma and allergic disorders. The purpose of the present study was to evaluate the bioequivalence of two azelastine hydrochloride tablets, Azeptin^TM (Bu Kwang Pharmaceutical Co., Ltd.) and Azela^TM (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 22.44±2.01 years in age and 61.99±6.18㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After two tablets containing 1㎎ of azelastine hydrochloride per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of azelastine in serum were determined using HPLC with fluorescence detector. Pharmacokinetic parameters such as AUC_t, C_max and T_max were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC_t, C_max and T_max between two tablets were -6.45%, -2.60% and -7.14%, respectively, when calculated against the Azeptin^TM tablet. The powers (1-β) for AUC_t and C_max were 96.65% and 88.47%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 14.40% and 17.65% for AUC_t and C_max, respectively). The 90% confidence intervals were within ±20% (e.g., -14.87∼1.97 and -12.92∼7.72 for AUC_t and C_max respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Azela^TM tablet is bioequivalent to Azeptin^TM tablet.

니세틸 정(아세틸-엘-카르니틴 500 mg)에 대한 뉴로세틸 정의 생물학적 동등성

조혜영,김은아,정현철,심영순,임동구,오인준,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is naturally occurring molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, Nicetiler^TM (Dong-A pharmaceutical Co., Ltd.) and Neurocetil^TM (Kyung-Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration. Twenty six normal male volunteers, 22.80±2.76 year in age and 63.07 7.98㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 500㎎ of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. Pharmacokinetic parameters such as AUC_t, C_max and T_max were calculated and ANOVA was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC_t, C_max and T_max between two tablets were 2.72%, -0.65% and -8.42%, respectively, when calculated against the Nicetile^TM tablet. The powers (1-β) for AUC_t and C_max were 94.87% and 87.17%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 15.58% and 19.16% AUC_t and C_max, respectively). The 90% confidence intervals were within ±20% (e.g., -11.84∼6.41 and -10.57∼11.88 for AUC_t and C_max, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Neurocetil^TM tablet is bioequivalent to Nicetile^TM tablet.

리마틸 정(부시라민 100 mg)에 대한 부시린 정의 생물학적 동등성

조혜영,이문석,오인준,김동현,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Bucillamine is a novel cysteine derivative with two free intramolecular sulfhydryl groups, and has a preventive and therapeutic effect on adjuvant arthritis, suggesting its antirheumatic action. With respect to the effect on the immune system, bucillamine-exerted such immunoregulating actions are to nomalize an excessive reduction or acceleration in immune reaction. It is useful not only in patients with early stage of rheumatoid arthritis (RA) but also in those with active RA retained for more than 10 years. The purpose of the present study was to evaluate the bioequivalence of two bucillamine tablets, Rimatil^TM (Chong Kun Dang Pharmaceutical Co., Ltd.) and Bucilin^TM (Kuhn Il Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers. 23.67±2.09 years in age and 65.03±6.73㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After three tablets containing 100㎎ of bucillamine per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of bucillamine in serum were determined using GC/MS with mass selective detector. Pharmacokinetic parameters such as AUC_t, C_max and T_max were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC_t, C_mex and T_max between two tablets were -0.29%, -3.20% and 8.22%, respectively, when calculated against the Rimatil^TM tablet. The powers (1-β) for AUC_t and C_max were 84.31% and 91.16%, respectively. Minimum detectable differences (Δ) at α=0.10 and 1-β=0.8 were less than 20% (e.g., 18.58% and 16.51% for AUC_t and C_max, respectively). The 90% confidence intervals were within ±20% (e.g., -12.77∼12.20 for AUC_t and -14.30∼7.90 for C_max). Two parameters met the criteria of KFDA for bioequivalence, indicating that Bucilin^TM tablet is bioequivalent to Rimatil^TM tablet.

딜라트렌 정(카르베딜롤 25 mg)에 대한 카베롤 정의 생물학적 동등성

조혜영,이문석,박순철,임동구,문재동,이용복 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

Carvedilol is an antihypertensive and antianginal compound that combines nonselective beta-adrenoceptor blocking and vasodilation properties and is devoid of intrinsic sympathomimetic activity. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, Dilatrend^TM (Chong Kun Dang Pharmaceutical Co., Ltd.) and Carvelol^TM (Dae Won Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The carvedilol release from the two carvedilol tablets in vitro was tested using KP ⅦI Apparatus Ⅱ method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB80 into water). Eighteen normal male volunteers, 24.22±1.86 years in age and 64.81±4.56㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 25㎎ of carvedilol was orally administered, blood was taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two carvedilol tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as AUC_t, C_max and T_max were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed AUC_t, and C_max. The results showed that the differences in AUC_t, C_max and T_max between two tablets based on the Dilatrend^TM were 2.23%, -2.00% and 0.00%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 13.55% and 17.61% for AUC_t and C_max respectively). The powers (1-β) at α=0.05, Δ=0.2 for AUC_t and C_max were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ±20% (e.g., -5.69~10.16 and -12.30~8.30 for AUC_t and C_max, respectively). There were no sequence effect between two tablets in logarithmically transformed AUC_t and C_max. The 90% confidence intervals using logarithmically transformed were within the acceptance range of log(0.8) to log(l.25) (e.g., 0.95~1.11 and 0.89~1.09 for AUC_t and C_max, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that Carvelol^TM tablet is bioequivalent to Dilatrend^TM tablet.

딜라트렌정(카르베딜롤 25mg)에 대한 카베롤 정의 생물학적 동등성

조혜영,이문석,박순철,임동구,문재동,이용복 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.4

Carvedilol is an antihypertensive and antianginal compound that combines nonselective beta-adrenoceptor blocking and vasodilation properties and is devoid of intrinsic sympathomimetic activity. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, Dilatrend^TM (Chong Kun Dang Pharmaceutical Co., Ltd.) and Carvelol^TM (Dae Won Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The carvedilol release from the two carvedilol tablets in vitro was tested using KP VII Apparatus Ⅱ method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB80 into water). Eighteen normal male volunteers, 24.22±1.86 years in age and 64.81±4.56 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 25 mg of carvedilol was orally administered, blood was taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two carvedilol tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as AUC_t C_max and T_max were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed AUC_t and C_max The results showed that the differences in AUC_t C_max and T_max between two tablets based on the Dilatrend^TM were 2.23%, -2.00% and 0.00%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=8 were less than 20% (e.g., 13.55% and 17.61% for AUC_t and C_max respectively). The powers (1-β) at α=0.05, Δ=0.2 for AUC_t and C_max were 98.08% and 88.81%, respectively. The 90% confidence intervals were within 20% (e.g., -5.69∼10.16 and -12.30∼8.30 for AUC_t and C_max, respectively). There were no sequence effect between two tablets in logarithmically transformed AUC_t and C_max, The 90% confidence intervals using logarithmically transformed were within the acceptance range of log(0.8) to log(1.25) (e.g., 0.95∼1.11 and 0.89∼1.09 for AUC_t and C_max respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that Carvelol^TM tablet is bioequivalent to Dilatrend^TM tablet.

아마릴 정(글리메피리드 2㎎)에 대한 글리메드 정의 생물학적 동등성

조혜영,박은자,강현아,백승희,이석,김세미,문재동,이용복 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.2

The purpose of the present study was to evaluate the bioequivalence of two glimepiride tables, Amaryl^(?)(Handok/Aventis Pharm. Co., Ltd.) and Glimed (Kuhn Ⅱ Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The glimepiride release from the two glimepiride formulations in vitro was tested using KP Ⅷ Apparatus Ⅱ method with a variety of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB 80 into each dissolution medium). Twenty six healthy male subjects, 22.65±2.19 years in age and 66.55±8.85 kg in body weight, were divided into two groups and randomized 2×2 cross-over study was employed. After one tablet containing 2 ㎎ as glimepiride was orally administered, blood was taken at predetermined time intervals and the concentrations of glimepiride in serum were determined using HPLC method with UV detctor. The dissolution profiles of two formulations were similar at all dissolution media. Besides, the pharmacokinetic parameters such as AUC_(t), C_(max) and untransformed T_(max). The results showed that the differences between two formulations based on the Amaryl were -3.70, -8.28 and 0.61% for AUC_(t), C_(max) and T_(max), 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(1.25)(e.g., log(0.84)∼log(1.04) and log(0.82)∼log(1.03) for AUC_(t) and C_(max), respectively). Thus, the criteria of the KFDA guideline for the bioequivalence were satisfied, indicating Glimed tablet and Amaryl tablet were bioequivalent.

리스페달 정(리스페리돈 2㎎)에 대한 리스펜 정의 생물학적 동등성

조혜영,박은자,강현아,백승희,이석,박찬호,문재동,이용복 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.2

The purpose of the present study was to evaluate the bioequivalence of two risperidone tablets, Risperdal (Janssen Korea Co., Ltd) and Rispen (Myung In Pharm. Co., Ltd), according to the guidelines of Korea Food and Drug Administration (KFDA). The risperione release from the two risperidone formulations in vitro was tested using KP Ⅷ Apparatus Ⅱ method with various of dissolution media (pH 1.2, 4.0, 6.8 butter solution and water). Twenty four healthy male subjects, 23.33±2.10 years in age and 69.24±8.05 kg in body weight, were divided into two groups and a randomized 2×2 crossover study was employed. After one tablet containing 2 ㎎ as risperidone was orally administered, blood was taken at predetermined time intervals and the concentration of risperidone in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. Besides, the pharmacokinetic parameters such as AUC_(t), C_(max) were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUC_(t), C_(max) and untransformed T_(max). The results showed that the differences between two formulations based on the Risperdal were 0.20, -1.29 and -11.09% for AUC_(t), C_(max) and T_(max), 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(1.25) (e.g., log(0.90)∼log(1.03) and log(0.84)∼log(1.09) for AUC_(t) and C_(max), respectively). Thus, the criteria of the KFDA guideline for the bioequivalence were satisfied, indicating Rispen tablet and Risperdal tablet were bioequivalent.

스프렌딜 지속정(펠로디핀 5㎎)에 대한 스타핀 지속정의 생물학적동등성

조혜영,강현아,이석,백승희,박은자,최후균,문재동,이용복 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.4

Felodipine is a calcium antagonist that lowers blood pressure by reducing peripheral resistance by means of a direct, selective action on smooth muscle in arterial resistance vessels. Furthermore, it have been approved for the effective in angina pectoris and cardiac failure. The purpose of the present study was to evaluate the bioequivalence of two felodipine extended release (ER) tablets, Splendil (YuHan Corporation) and Stapin (Hana Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). THe felodipine release from the two felodipine formulations in vitro was tested using KP Ⅷ Apparatus Ⅱ method at pH 6.5 buffer solution. Twenty six healthy male subjects, 22.73±1.78 years in age and 66.66±7.28 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After two tablets containing 5 ㎎ as felodipine were orally administered, blood sample was taken at predetermined time intervals and the concentrations of felodipine in serum were determined using column-switching HPLC method with UV detector. The dissolution profiles of two formulations were similar at pH 6.5 buffer solution. Besides, the pharmacokinetic parameters such as AUG_(t), C_(max) and T_(max) were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUC_(t) and C_(max) and untransformed T_(max). The results showed that the differences between two formulations based on the Splendil were 2.53%, 1.32% and 18.32% for AUC_(t), C_(max) and T_(mzx), 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(1.25) (e.g., log(0.86)∼log(1.20) and long(0.89)∼long(1.23) for AUC_(t) and C_(max), respectively). Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Stapin ER tablet and Splendil ER tablet are bioequivalent.