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.

무코스타정(레바미피드 100mg)에 대한 레바미드 정의 생물학적 동등성

조혜영,정현철,오인준,문재동,이용복 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.4

Rebamipide is a novel anti-gastric ulcer agent that has been reported to increase the synthesis of mucus, to increase the mucosal concentration of prostaglandin, and to promote rapid ulcer healing. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, Mucosta^TM (Otsuka Korea Pharmaceutical Co., Ltd.) and Rebamide^TM (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The rebamipide release from the two rebamipide tablets in vitro was tested using KP VII Apparatus II method at pH 6.8 dissolution media. Twenty normal male volunteers, 24.20±2.26 years in age and 66.19±9.41 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 100 mg of rebamipide was orally administered, blood was taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two rebamipide tablets were very similar at pH 6.8 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. The results showed that the differences in AUC_t C_max and T_max between two tablets based on the Mucosta^TM were -2.57%, 5.77% and -1.47%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 12.62% and 17.63% 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 above 99.00% and 88.56%, respectively. The 90% confidence intervals were within 20% (e.g., -9.96∼4.82 and -4.54∼16.09 for AUC_t and C_max respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Rebamide^TM tablet is bioequivalent to Mucosta^TM tablet.

레보프라이드 정(레보설피리드 25㎎)에 대한 레보피드 정의 생물학적 동등성

조혜영,강현아,문재동,이용복 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.2

Levosulpiride is the levo-enantiomer form of racemic sulpiride, a benzamide derivative selectively inhibiting dopaminergic D_2 receptors at the trigger zone both in the central nervous system and in the gastrointestinal tract. The purpose of the present study was to evaluate the bioequivalence of two levosulpiride tablets, Levopride (SK Pharmaceutical Co., Ltd.) and Levopid (Dae Won Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The levosulpiride release from the two levosulpiride 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 and water). Twenty eight normal male volunteers, 23.82±3.26 years in age and 69.13±8.58 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 levosulpiride was orally administered, blood was taken at predetermined time intervals and the concentrations of levosulpiride in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two levosulpiride 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 logarithmically transformed AUC_t and C_max and untransformed T_max. The results showed that the differences in AUC_t, C_max and T_max between two tablets based on the Levopride were -1.17%, 1.20% and -1.09%, respectively. There were no sequence effects between two tablets 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(0.93)∼log(1.07) and log(0.90)∼log(1.14) for AUC_t and C_max, respectively). The 90% confidence interval using untransformed data was within ±20% (e.g., -19.47∼16.20 for T_max). All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Levopid tablet is bioequivalent to Levopride tablet.

알기론 정(브롬화 시메트로피움 50 mg)에 대한 알피트 정의 생물학적 동등성

조혜영,문재동,이용복 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Cimetropium bromide, a quaternary ammonium compound which is chemically related to scopolamine, exhibits its antispasmodic activity by competing with acetylcholine for the muscarinic receptors of the smooth muscle of gastrointestinal tract. The drug has been used for the treatment of various disorders involving spasms of the musculature of the gastrointestinal, biliary and genitourinary tracts. The purpose of the present study was to evaluate the bioequivalence of two cimetropium bromide tablets, Algiron™ (Boehringer Ingelheim Korea Ltd.) and Alpit™ (Hana Phamaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KDFA). The cimetropium bromide release from two cimetropium bromide 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 and water). Twenty normal male volunteers, 25.25 ± 2.10 years in age and 65.76 ± 6.39 ㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After three tablets containing 50 ㎎ of cimetropium bromide per tablet were orally administered, blood was taken at predetermined time and the concentrations of cimetropium bromide in serum were determined using HPLC method with UV detector. The dissolution profiles of two cimetropium bromide 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 Algiron™ were 2.19%, -5.97% and 3.49%, respectively. Minimum differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 13.71%, 19.05% and 15.11% for AUC_t, C_max and T_max, respectively). The powers (1-β) at α=0.05, Δ=0.2 for AUC_t, C_max and T_max were 97.79%, 83.22% and 95.60%, respectively. The 90% confidence intervals were within ±20% (e.g., -5.84∼10.21, -17.11∼5.18 and -5.35∼12.33 for AUC_t, C_max and T_max, respectively). There were no sequence effect between two tablets in logarithmically tanformed AUC_t, C_max. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., 0.94∼1.10 and 0.85∼1.05 for AUC_t, C_max, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that Alpit™ tablet is bioequivalent to Algiron™ tablet.

프레탈 정(실로스타졸 100 mg)에 대한 엘지실로스타졸 정의 생물학적 동등성

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

Cilostazol has both antithrombotic and cerebral vasodilating effects, and one of the mechanism is the selective inhibition of platalet cyclic AMP phosphodiesterase. Bioequivalence of two cilostazol tablets, the Pletaal^TM (Korea Otsuka Pharmaceutical Co.) and the LG Cilostazol^TM (LG Chemical Co.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen normal male volunteers (20∼29 years old) were randomly divided into two groups and a randomized 2×2 cross-over study was employed. After oral administration of Pletaal^TM or LG Cilostazol^TM tablet (100㎎ cilostazol), blood samples were taken at predetermined time intervals and the serum cilostazol concentrations were determined using an HPLC method with UV/VIS detector. The pharmacokinetic parameters (AUC_t, C_max and T_max) were calculated and ANOVA was utilized for the statistical analysis. The results showed that the differences in AUC_t, C_max and T_max between two tablets based on the Pletaal^TM tablet were -5.39%, 2.32% and 4.26%, respectively. The powers (1-β) for AUC_t, C-max, and T_max were 83.81%, 96.02% and 91.04%, respectively. Minimum detectable differences (Δ) and 90% confidence intervals were all less than ±20%. All these parameters met the criteria of KFDA for bioequivalence, indicating that LG Cilostazol^TM tablet is bioequivalent to Pletaal^TM tablet.

무코스타 정(레바미피드 100 mg) 에 대한 레바미드 정의 생물학적 동등성

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

Rebamipide is a novel anti-gastric ulcer agent that has been reported to increase the synthesis of mucus. to increase the mucosal concentration of prostaglandin, and to promote rapid ulcer healing. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, Mucosta^TM (Otsuka Korea Pharmaceutical Co., Ltd.) and Rebamide^TM (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The rebamipide release from the two rebamipide tablets in vitro was tested using KP Ⅶ Apparatus Ⅱ method at pH 6.8 dissolution media. Twenty normal male volunteers, 24.20±2.26 years in age and 66.19±9.41㎏ in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 100㎎ of rebamipide was orally administered, blood was taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two rebamipide tablets were very similar at pH 6.8 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. The results showed that the differences in AUC_t, C_max and T_max between two tablets based on the Mucosta^TM were -2.57%, 5.77% and - 1.47%, respectively. Minimum detectable differences (Δ) at α=0.05 and 1-β=0.8 were less than 20% (e.g., 12.62% and 17.63% 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 above 99.00% and 88.56%, respectively. The 90% confidence intervals were within ±20% (e.g., -9.96~4.82 and -4.54~16.09 for AUC_t and C_max respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that Rebamide^TM tablet is bioequivalent to Mucosta^TM tablet.

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.

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.