비유피-4 정(염산프로피베린 20㎎)에 대한 건일염산프로피베린 정의 생물학적동등성

조혜영,박은자,강현아,백승희,김세미,박찬호,오인준,문재동,이용복 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.5

The purpose of the present study was to evaluate the bioequivalence of two propiverine hydrochloride tablets. BUP-4 (Jeil Pharm. Co., Ltd.) and Kuhnil Propiverine Hydrochloride (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The propiverine release from the two propiverine hydrochloride 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 solutions, water and blend of polysorbate 80 into pH 6.8). Twenty six healthy male subjects, 23.73 ± 2.79 years in age and 67.04 ± 7.93 kg in body weight, were divided into two groups and a randomized 2 x 2 cross-over study was employed. After one tablet containing 20 mg as propiverine hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of propiverine in serum were determined using HPLC method with UV detector. The dis-solution profiles of two formulations were similar at all dissolution media. Besides, the pharmacokinetic parameters such as AUC" C _(max) and T _(max) were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUC, C_(max), and untransformed T_(max). The results showed that the differences between two formulations based on the BUP-4 were 0.17%, 7.98% and 4.55% for AUC,, C_(max), and respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically trans-formed data were within the acceptance range of log(0.8) to log(1.25) (e.g., log(0.88)-log(l .12) and log(0.90)-log(l.15) for AUC, and _(max), respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Kuhnil Propiverine Hydrochloride tablet was bioequivalent to BUP-4 tablet.

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.

흑두 추출물이 모발 주기 anagen 시기의 증식과 분화에 미치는 영향

조영롱,이은정,조경혜 서울여자대학교 2010 자연과학연구논문집 Vol.22 No.-

A hair follicle is one of complex miniorgans in human body which has a life cycle of anagen, catagen and telogen. The three stages occur periodically and it is reported that this cycle is controlled by the balance of Bmp and noggin. This study attempts to verify in a molecular level if a Glycine Semen nigra extract known as a hair restorer has positive effect on maintaining autonomous anagen stage of DP cells isolated from 1 day-old rat back skin by expressing Bmp and noggin. It was proven that the Glycine Semen nigra extract stimulates mRNA expression of bmp4, bmp6 and their receptor bmpr1a, which maintains anagen stage and stimulates differentiation. The effect of Glycine Semen nigra extract on stimulating differentiation of DP cells was also verified as the extract increases the expression of lef1 and other differentiation marker genes (wif1, akp2, alx4) for differentiation and the enzyme activity of alkaline phosphatase. It was observed that Glycine Semen nigra extract induces anagen phase and increases the gene expression of Bmp antagonist noggin which stimulates proliferation of DP cells. The expression of various growth factors (fos, vegf, fgf2) related to the proliferation of DP cell and hair follicle increases. The expression of wnt7a, which maintains anagen and stimulates cell multiplication, and its effector β-catenin also increased. Therefore, it was verified that Glycine Semen nigra extract has positive effect on hair growth by maintaining anagen stage, at which multiplication and differentiation of follicular cells actively occur. Glycine Semen nigra extract is expected to be used as a hair tonic or a hair growth promoter that maintains anagen stage and healthy hair.

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.

계배 대퇴 근육 세포의 c-fos 유전자 발현 : 신호전달물질 및 신경세포와의 공동배양 효과 Effect of Signal Transduction Regulators and Co-culture with Chick Spinal Cord Neurons

조경혜,김은주 서울여자대학교 자연과학연구소 1995 자연과학연구논문집 Vol.6 No.-

근육세포의 성장 및 분화는 인접한 신경세포에서 유리되는 신경전달물질에 의해 여러 경로를 통해 상호 조절된다. 본 실험에서는 계배 신경세포와 근육세포를 공동배양하여 근육세포에서의 c-fos 발현을 조사하였으며 NGF, EGF, Ca++ionophore, PMA(Phobol 12-myristate 13-acetate)등을 근육세포에 처리함으로써 근육세포의 c-fos 발현 경로를 알아보고자 하였다. 계배 근육세포에서 c-fos 암원 유전자의 발현을 보기위해 Northern bolt과 slot blot 분석을 실시하였다. 발생 12일째된 계배 근육세포 배양 2일째에는 c-fos 발현이 증가되기 시작하여 5일째는 다소 감소하며 6일째는 더 이상 변화를 보이지 않았으며 신경세포와의 공동배양에서는 2일 후 c-fos 유전자의 유도를 관찰하였다. 분화된 근육세포에 EGF를 처리시 신속한 c-fos 발현 유도를 관찰하였으나 NGF를 처리시 그 효과를 관찰할 수 없었다. 이는 외부 신호 전달 물질 EGF와 신경말단의 시냅스 전달이 근육세포에서의 c-fos 발현을 조절하는데 영향을 미치는 것으로 생각된다. 또한, Ca++ionophore (A23187)를 처리시 c-fos 암원 유전자의 신속한 증가를 관찰하였으나 PMA를 처리시는 주목할 만한 발현 증가를 볼 수 없었다. 이러한 결과는 Ca++이라는 이차 전령신호가 근육세포내의 c-fos 발현을 가져올 수 있음을 시사한다. 이들 결과로 부터 계배 근육세포에서의 c-fos 발현은 외부자극에 반응하여 초기에 일어나며, 근육세포의 증식과 분화에 관여하리라 생각된다. Growth and differentiation of muscle cells were regulated by synaptic interaction of nerve endings and post synaptic events. This study was aimed to elucidate effects of co-culture with spinal cord neurons and four different signal transduction regulators, NGF, EGF, Ca^++ ionophore (A023187) and PMA (Phorbol 12-myristate 13-acetate) on an expression of c-fos in chick embryonic skeletal muscle cells. Muscle cells were prepared from 12-day-old chick embryonic skeletal muscle cultured for 6 days. An increase in the expression of c-fos was observed after 2 days in culture, it continued for 3 more days, then declined after day 5. after co-culture for 2 days, the c-fos gene expression was increased in the differentiated skeletal muscle cells. The expression of c-fos in the differentiated muscle cells was increased within 60 minutes after treatment with EGF but its expression by NGF was not observed. These findings suggest that extracellular signal transmission through EGF and post synaptic has important roles on the regulation of the c-fos gene expression in differentiated muscle cells. The treatment with Ca^++ ionophore (A23187) in muscle cells induced the c-fos gene expression but PMA did not. These results reveal that the signal transduction pathway through the Ca^++ affects c-fos gene expression in skeletal muscle cells. Taken together, the expression of the c-fos is an early event in the response to external stimuli and plays an important role in proliferation and differentiation of skeletal muscle cells.

Nicotine이 계태장기조직의 효소활성에 미치는 영향

조경혜,유은정 서울여자대학교 자연과학연구소 1991 자연과학연구논문집 Vol.2 No.-

임산부 흡연시 담배의 다양한 성분가운데, nicotine이 모체의 대사변동을 통해 간접적으로 또는 태반 융모간 혈류를 따라 직접적으로 태아에게 미치는 영향을 효소학적으로 검증하고자 본 연구를 수행하였다. 인체와의 내성의 차이를 고려하여, 발생중인 계태(8일째)에 0.5ml의 nicotine 용액을 농도별로 (대조군, 제1군:0.206mg/egg, 제2군:0.412mg/egg, 제3군:0.618mg/egg, 제4군:0.824mg/egg) 주입하고, 10일을 더 발육시킨 후 각 장기를 적출하여 마쇄하고 원심분리한 상등액을 시료로 하여 효소활성을 측정한 결과, 대조군에 대한 제2군에서의 specific activity비율이 다음과 같이 증감되었다. Alkaline phosphatase는 폐에서 5.4배, 신장 3.4배, 간과 대퇴부 1.3배, 뇌와 소장에서 1.2배, 심장 1.1배의 증가를 보였고, 위에서는 50% 감소되었다. ATPase는 폐 1.7배, 간 1.6배, 신장에서 1.4배의 증가를 보였고, 심장과 소장에서 1.13배, 위에서 1.07배의 활성을 나타내었으며, 뇌와 대퇴부에서는 오히려 감소하여 각각 90%수준의 specific activity를 보였다. MDH는 152%와 118%로 각각 증가된 폐와 신장을 제외한 모든 장기에서 specific activity가 낮아졌는데, 그 감소비율은 간 29%, 뇌 25%, 위 24% 대퇴부 20%, 심장 17%, 소장 6%로 나타났다. 5'-Nucleotidase는 폐 6.6배, 신장 1.8배, 대퇴부 1.34배, 심장 1.29배, 간 1.1배의 증가를 보인 반면, 뇌와 위, 소장은 대조군에 비해 각각 17%, 22%, 12% 감소를 보였다. Arginase는 폐, 신장에서 각각 1.7배와 1.4배의 두드러진 증가를 보였으며, 뇌와 소장은 1.3배, 간과 대퇴부는 1.1배의 증가가 있었으나, 심장과 위에서는 9%와 19%의 감소를 보여주었다. 소화 및 근육장기에 비해 독성물질을 방어하거나 대사 및 배설하는 장기(간, 폐, 신장)에서 유의적인 증감을 확인할 수 있었는데 특히 폐에서 나타난 큰 변화는 흡연으로 인한 폐조직 손상과는 독립적으로 nicotine이 단독효과를 갖는다는 점을 시사해 준다. 간에서 보다 신장에서의 현저한 효과는 avian species의 대사적 특성으로 말미암아 간기능 일부를 신장이 담당하였기 때문에 나타난 결과로 보며, 이들 enzyme의 활성변화가 사람에게서도 나타나는 가를 확인하기 위해서는 쥐나 원숭이등의 동물실험이 더 부가되어야 하리라 생각된다. In order to study the effect of nicotine on the metabolic activities of the fetal tissues, the changes of enzymatic activities have been investigated in the chick embryonic organs treated with nicotine. Infection concentration which expressed low mortality and ascertained significant change of specific activity is 0.412mg/egg group and each organocellular enzymatic activity is as like follow: 1. Specific activity of alkaline phosphatase is significantly increased in lung, kidney and liver but decreased in stomach. 2. Specific activity of ATPase is increased in lung, liver, and kidney but decreased in brain & thigh muscle. 3. Specific activity of malate dehydrogenase is decreased in liver, brain, stomach, thigh muscle, and heart, but increased in lung and kidney. 4. Specific activity of 5'-nucleotidase is increased in lung, kidney, thigh muscle, and heart but decreased in brain, stomach and intestine. 5. Specific activity of arginase is increased in lung, kidney, brain, and intestine but decreased in heart and stomach. Significant changes of specific activity are ascertained in organs which protect, metabloize or excret toxic materials rather than digestive or muscular organ. In particular, large scale change expressed in lung suggested that the nicotine affccts not only tissue damages by smoking but also the metabolic changes of the fetal tissues at the cellular levels. More remarkable changes in kidney result from metabolic specificity of avian species which kidney is in charge of a part of liver function.

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.

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.

Minoxidil에 의한 모발절대휴지기 탈출 유도 효과

이은정,조영롱,조경혜 서울여자대학교 자연과학연구소 2011 자연과학연구논문집 Vol.23 No.-

Hair follicle (HF), a small physiological organ in the human body which produces hair, repeats a four-phased hair cycle consisting of anagen, catagen, telogen, and exogen phases and affects the growth, maintenance, and loss of hair. Recent studies revealed that the hair growth and loss are controlled by the balance between bmp and nog expressed from dermal papilla cells (DP cells) which control the physiological characteristics of the hair growth cycle and that a phase transition from refractory telogen phase to competent telogen phase, caused from the reduction in expression of bmp gene in the telogen phase, is indispensible for the regeneration of hair cycle. This study is conducted to verify the effect of minoxidil, a depilatory lotion widely used around the globe on the molecular mechanism in the hair cycle process occurring in the DP cells, especially in the expression of bmp and nog genes. DP-enriched cells were separated and cultured from the back skin of 1 day-old new born rats and observed the effects after processing minoxidil on the cells. Minoxidil reduced the expression of bmp4 and bmp6 genes, which stimulate differentiation but inhibit multiplication of DP cells in the hair cycle control process, and reduced the expression of bmprla gene, as its receptor. Minoxidil also reduced the expression of nog genes known as an antagonist of bmp produced from DP cells and an essential element in the telogen-anagen phase transition. From this results, minoxidil induced the DP cells to stay at the competent telogen phase, a prior phase of the initiation of the anagen phase, and to escape from refractory telogen phase of the hair cycle. Also, minoxidil induced DP cells to an ‘undifferentiated state of hair cell' of competent telogen phase, a prior phase of early anagen phase, rather than that inducing the cell to an initiation phase of hair cycle, the anagen phase. Minoxidil reduced the expression of nog gene which is an essential element in the regeneration of hair cycle, but increased the expression of bfgf gene, a upstream growth factor which stimulates the expression of nog and vegf genes which foster the growth of DP cell. Thus, it can be suggested that there is possibility that minoxidil indirectly affects telogen-anagen phase transition and the initiation of anagen phase. In conclusion, this study verified that minoxidil leads escape from refractory telogen phase of a hair growth cycle and thereby reduces the period of the telogen phase. Key words:dermal papilla cells, minoxidil, bmp, noggin, hair cycle.

[P5-51] Characterization of a bifunctional chitinase-fibrinolytic enzyme of Bacillus licheniformis isolated from Fermented Shrimp paste

Eun Kyung Cho,Yu Jung Jung,Hyo Ju Song,Hea Eun Cho,Eun Kyung Cho,Sang Wan Gal,Young Ju Choi 한국식품영양과학회 2008 한국식품영양과학회 학술대회발표집 Vol.2008 No.10