타크린염산염의 피부투과도 연구

조영주,최후균 조선대학교 약학연구소 1998 藥學硏究誌 Vol.19 No.1

Tacrine (9-amino-l,2,3,4-tetrahydroacridine), a reversible acetylcholinesterase inhibitor, is used for treating the symptoms of mild to moderate Alzheimer's disease. On per oral administraton, however, tacrine appears to exhibit side-effects such as dose-dependent and reversible hepatotoxicity. To overcome this disadvantage, we investigated the feasibility of developing transdermal drug delivery system for tacrine. The effects of various solvents on the permeation rate of tacrine salt across hairless mouse skin were examined using flow-through diffusion cell system. The solubility of tacrine salt in the solvents used in percutaneous absorption study was obtained using equilibrium solubility method. Among tested vehicles, octanol and propylene glycol/oleyl alcohol mixtures showed the highest permeability of tacrine salt. Theoretically, the higher the solubility, the lower the permeation rate. However, it was not possible to demonstrate any correlationship between the solubility and the percutaneous absorption rate of tacrine salt. The results indicate that some of the solvents may change the barrier property of the skin and/or carrier mechanism may be involved.

플루란 아세테이트 미립구를 이용한 단백질 전달 시스템 개발

나건,최후균 한국약제학회 2006 Journal of Pharmaceutical Investigation Vol.36 No.2

Piroxicam Plaster의 개발에 관한 연구

이정화,최후균 조선대학교 약학연구소 1998 藥學硏究誌 Vol.19 No.1

To develop piroxicam transdermal plaster, the effect of adhesive matrix and various vehicles on the permeation of piroxicam across hairless mouse skin was evaluated. The permeation rate of piroxicam was higher from polyisobutylene adhesive matrix than from acrylic adhesive matrix. Piroxicam seemed to be saturated in acrylic adhesive at the concentration range of 8.3% - 11.1%. Isopropyl myristate did not have significant effect on the permeation rate of piroxicam from acrylic adhesive matrix. However, it increased permeation rate of piroxicam from rubber adheisve matrix. When various permeation enhancers were tested in rubber adhesive matrix, transcutol showed the best results. Considering the measured solubility of piroxicam in those enhancers, it can be concluded that no relationship can be found between the thermodynamic activity of piroxicam and the permeation rate across the skin. It also indicates that the mechanism of the permeation enhancers is the change in the barrier property of the skin.

기초화장용 제품 중 크림과 로션제의 안정성 평가방법

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

This study was attempted to develop the physicochemical and morphological stability test methods for the cream and lotion formulations among the cosmetic foundations and to provide the guidance for the stability methods with respect to basic emulsions and creams. With these developed stability test methods, we can evaluate the expired date or life time of the available basic cosmetics, especially basic lotions and creams. Also, the stability test methods established in this study can be used as a guideline to test physical and morphological stability of cosmetics in the future. Thus, we selected two types of basic cosmetics such as lotions and creams made by four different cosmetic companies and applied them to stability test methods depending on the temperature changes such as temperature cycling and freezing-thawing cycling test. After the temperature changes, the conductivity, turbidity, particle size, creaming ratio and pH changes of the creams and lotions were evaluated and morphological changes such as crystal formation, oder, color and feeling of the creams and lotions were also tested. As the results of the stability tests, all the tested creams and lotions except for one lotion were stable. Therefore, it may be concluded that these short-term accelerated stability tests as physical stability test depending on the temperature change study were suitable for the stability testing methods for the basic cosmetics and may be useful for the establishment of the guideline for the stability test of cosmetics.

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.

Oxidative Degradation of a Drug during the Course of Diffusion Across the Skin

Choi, Hoo-Kyun 朝鮮大學校 1998 藥學硏究誌 Vol.19 No.2

Degradation of a compound with a hydroxyl group during the course of its diffusion across the skin was investigated. Based on the experimental findings of a shortened retention time of a degradant peak from post-diffusion samples and from the ability to evaporate radioactivity from such samples, it seems that during diffusion the parent compound degrades into a more hydrophilic product which is then oxidized. A tritium label at the carbon with a hydroxyl group was released as a tritiated water. When the post-diffusion samples were left open to the air allowing evaporation of water, there was a corresponding decrease in radioactivity of such samples. There was a linear relationship between the time left open and the fraction of radioactivity lost. When such samples were fractionated by HPLC, and then had their radioactivities measured by scintillation counting, two peaks were identified. The first peak, which may be attributable to tritiated water, was eluted at the came retention time as the solvent front. The second peak eluted at the retention time of the parent compound. When the evaporation/loss of radioactivity experiment was repeated using a ^(14)C-labeled compound there was no significant loss of radioactivity, indicating that the earlier loss with 'H-labeled compound was related to the formation and loss of tritiated water.

SIRT1-Mediated FoxO1 Deacetylation Is Essential for Multidrug Resistance-Associated Protein 2 Expression in Tamoxifen-Resistant Breast Cancer Cells

Choi, Hoo-Kyun,Cho, Kyoung Bin,Phuong, Nguyen Thi Thuy,Han, Chang Yeob,Han, Hyo-Kyung,Hien, Tran Thi,Choi, Hong Seok,Kang, Keon Wook American Chemical Society 2013 Molecular pharmaceutics Vol.10 No.7

<P>Our previous studies have shown that multidrug resistance protein 2 (MRP2) is overexpressed in tamoxifen-resistant MCF-7 breast cancer cells (TAMR-MCF-7 cells) and forkhead box-containing protein, O subfamily1 (FoxO1), functions as a key regulator of multidrug resistance 1 (MDR1) gene transcription. This study aimed to investigate the role of FoxO1 in regulating MRP2 gene expression in TAMR-MCF-7 cells. The proximal promoter region of the human MRP2 gene contains four putative FoxO binding sites, and MRP2 gene transcription was stimulated by FoxO1 overexpression in MCF-7 cells. Subcellular fractionation and immunoblot analyses revealed that basal MRP2 expression and nuclear levels of FoxO1 were enhanced in TAMR-MCF-7 cells compared to MCF-7 cells and the enhanced MRP2 gene transcription was suppressed by FoxO1 siRNA. Because nuclear localization of FoxO1 is regulated by SIRT1 deacetylase, we were further interested in whether SIRT1 is involved in MRP2 expression. Overexpression of SIRT1 with FoxO1 potentiated the gene transcriptional activity of MRP2, and the basal activity and expression of SIRT1 was increased in TAMR-MCF-7 cells. In addition, SIRT1 inhibition reduced both the nuclear FoxO1 levels and MRP2 expression and enhanced cytotoxic effects of paclitaxel and doxorubicin in TAMR-MCF-7 cells. These results suggest that FoxO1 activation via SIRT1-mediated deacetylation is closely related with up-regulation of MRP2 in TAMR-MCF-7 cells.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mpohbp/2013/mpohbp.2013.10.issue-7/mp400287p/production/images/medium/mp-2013-00287p_0008.gif'></P>

Transdermal Drug Delivery

( Hoo Kyun Choi ) 한국피부장벽학회 2011 한국피부장벽학회지 Vol.13 No.1

Recently, various kinds of drug delivery systems have been developed to improve therapeutic efficacy, to reduce side effects, and to provide better patient compliance. Many different ways of administration have been used for the development of the drug delivery systems, including oral, transdermal, nasal, transmucosal, buccal, and pulmonary routes. Among those, transdermal drug delivery system has several advantages such as reduced side effects, better therapeutic efficacy, and reduced dosing frequencies. Transdermal delivery of pharmacologically active agents has been extensively studied for the past 40 years. Despite the strong efforts, currently, only about 40 products are in market on about 20 drug molecules, mainly due to the barrier properties of the stratum corneum. Various approaches to overcome the barrier function of skin through physical and chemical means have been broadly studied. The development of an effective transdermal delivery system is dictated by the unique physicochemical property each drug molecule possesses. Various physical and chemical approaches for transdermal flux enhancement will be discussed.

Oxidative Degradation of a Drug during the Course of Diffusion Across the Skin

Choi, Hoo-Kyun The Pharmaceutical Society of Korea 1997 Archives of Pharmacal Research Vol.20 No.6

Degradation of a compound with a hydroxyl group during the course of its diffusion across the skin was investigated. Based on the experimental findings of ashortened retention time of a degradant peak from post-diffusion samples and from the ability to evaporate radioactivity from such samples, it seems that during diffusion the parent compound degrades into a more hydrophilic product which is then oxidized. A tritium label at the carbon with a hydroxyl group was released as a tritiated water. When the post-diffusion samples were left open to the air allowing evaporation of water, there was a corresponding decrease in radioactivity of such samples. There was a linear relationship between the time left open and the fraction of radioactivity lost. When such samples were fractionated by HPLC, and then had their radioactivities measured by scintillation counting, two peaks wre identified. The first peak, which may be attributable to tritiated water, was eluted at the same retention time as the solvent front. The second peak eluted at the retention time of the parent compound. When the evaporation/loss of radioactivity experiment was repeated using a $^{14}C$-labeled compound there was no significant loss of radioactivity, indicating that the earlier loss with $^{3}H$-labeled compound was related to the formation and loas sof tritiated water.

Transdermal Delivery of Boiactive Peptides

( Hoo Kyun Choi ) 한국약제학회 1990 한국약제학회 총회 및 학술대회 요지집 Vol.- No.-