• Molecules and Cells
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• 제42권1호
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• pp.36-44
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• 2019

Alzheimer's disease (AD) is the most frequent age-related human neurological disorder. The characteristics of AD include senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. ${\beta}-Amyloid$ ($A{\beta}$) peptide is the predominant proteinaceous component of senile plaques. The amyloid hypothesis states that $A{\beta}$ initiates the cascade of events that result in AD. Amyloid precursor protein (APP) processing plays an important role in $A{\beta}$ production, which initiates synaptic and neuronal damage. ${\delta}-Catenin$ is known to be bound to presenilin-1 (PS-1), which is the main component of the ${\gamma}-secretase$ complex that regulates APP cleavage. Because PS-1 interacts with both APP and ${\delta}-catenin$, it is worth studying their interactive mechanism and/or effects on each other. Our immunoprecipitation data showed that there was no physical association between ${\delta}-catenin$ and APP. However, we observed that ${\delta}-catenin$ could reduce the binding between PS-1 and APP, thus decreasing the PS-1 mediated APP processing activity. Furthermore, ${\delta}-catenin$ reduced PS-1-mediated stabilization of APP. The results suggest that ${\delta}-catenin$ can influence the APP processing and its level by interacting with PS-1, which may eventually play a protective role in the degeneration of an Alzheimer's disease patient.

• Natural Product Sciences
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• 제28권3호
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• pp.143-152
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• 2022

In our study, sixteen known phenolic compounds, including quercetin (1), methyl gallate (2), caesalpiniaphenol C (3), 8S,8'S,7'R-(-)-lyoniresinol (4), 7,3',5'-trihydroxyflavanone (5), sappanchalcone (6), sappanone A (7), taxifolin (8), fisetin (9), fustin (10), (+)-catechin (11), brazilin (12), 3,4,5-trimethoxyphenyl β-ᴅ-glucopyranoside (13), 1-(2-methylbutyryl)phloroglucinol-glucopyranoside (14), (+)-epi-catechin (15), and astragalin (16) and one mixture of two conformers of protosappanin B (17/18) were isolated from the stems of Caesalpinia decapetala var. japonica. Their structures were elucidated based on a comparison of their physicochemical and spectral data with those of literature. To the best of our knowledge, this represents the first isolation of compounds 3, 4, 8, 9, and 10 from C. decapetala and compounds 13 and 14 from the Caesalpinia genus. All the isolated compounds were evaluated for their inhibitory effect against the α-glucosidase enzyme. Among them, two flavonols (1 and 9), one chalcone (6), and one homoisoflavanone (7) exhibited an inhibitory effect on α-glucosidase action with an IC₅₀ range value of 5.08-15.01 μM, stronger than that of the positive control (acarbose, IC₅₀ = 152.22 μM). Kinetic analysis revealed that compounds 1 and 9 showed non-competitive α-glucosidase inhibition, while the inhibition type was mixed for compounds 6 and 7.

• Journal of Pharmaceutical Investigation
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• 제37권3호
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• pp.197-203
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• 2007

A bioequivalence study of $Dilast^{TM}$ Capsule (Chong Kun Dang Pharma. Co., Ltd.) to $Ketas^{(R)}$ Capsule (Han Dok Pharma. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty eight healthy male Korean volunteers received each medicine at the ibudilast dose of 20 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of ibudilast were monitored by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for over a period of 36 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 36 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t\;and\;C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Dilast^{TM}$ $Capsule/Ketas^{(R)}$ Capsule were $log0.93{\sim}log1.06$ and $log0.93{\sim}log1.11$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Thus, our study demonstrated the bioequivalence of $Dilast^{TM}$ Capsule and $Ketas^{(R)}$ Capsule with respect to the rate and extent of absorption.

• 한국임상약학회지
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• 제28권2호
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• pp.146-153
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• 2018

Objective: Multi-regional clinical trials have been widely used for accelerating global drug development by multinational pharmaceutical companies. In this study, we aimed to review and analyze the international trends in regulations and guidelines on multi-regional clinical trials by regulatory authorities and international organizations, such as International Conference on Harmonisation, for referring to policies, including development of domestic guidelines for multi-regional clinical trials. Methods: The policies, regulations, and guidelines published by the US Food and Drug Administration, European Medicines Agency, Pharmaceuticals and Medical Devices Agency (Japan), and China Food and Drug Administration were searched, and the International Conference on Harmonisation E17 draft guideline was reviewed. Results: The regulatory authorities in developed countries have developed and implemented regulations and guidelines on multi-regional clinical trials to promote simultaneous global drug development and evaluate the regional differences in drug safety and efficacy. International Conference on Harmonisation developed the draft guideline for planning/designing of multi-regional clinical trials in 2016, which recommends the general principles for strategy-related issues and design of multi-regional clinical trials, and for protocol-related issues, such as consideration of regional variability, subject selection, dose selection, endpoints, comparators, overall sample size, allocation to regions, collecting information on efficacy and safety, and statistical analysis. Conclusion: It is important to understand the international regulatory requirements for designing and planning of multi-regional clinical trials for global drug development. Moreover, it is necessary to prepare multi-regional clinical trial guidelines in accordance with the Korean regulation for clinical trials and drug administration.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.510-516
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• 2015

In this review, lipid A, from its discovery to recent findings, is presented as a drug target and therapeutic molecule. First, the biosynthetic pathway for lipid A, the Raetz pathway, serves as a good drug target for antibiotic development. Several assay methods used to screen for inhibitors of lipid A synthesis will be presented, and some of the promising lead compounds will be described. Second, utilization of lipid A biosynthetic pathways by various bacterial species can generate modified lipid A molecules with therapeutic value.

• Macromolecular Research
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• 제8권5호
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• pp.199-208
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• 2000

The recent development of biodegradable polymers for drug delivery system (DDS) has been investigated. The biodegradable polymers for DDS are mainly discussed in two categories: one category is natural biodegradable polymers such as polysaccharides, modified celluloses, poly(${\alpha}$-amino acid)s, modified proteins, and microbial biodegradable polymers; the other is synthetic biodegradable polymers such as poly(ester)s, poly(ortho ester)s, poly(phosphazene)s, poly(anhydride)s, poly(alkyl cyanoacrylate)s, and multiblock copolymers. The bioconjugate polymeric drug delivery systems have been also proposed for the design of biocompatible polymeric controlled drug delivery.

• Bulletin of the Korean Chemical Society
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• 제32권10호
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• pp.3752-3755
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• 2011

• Safe Food
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• 제2권1호
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• pp.38-47
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• 2007

• 한국임상약학회지
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• 제21권3호
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• pp.249-255
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• 2011

Objective: To examine the drug use (prescribing) pattern of serious drug-drug interactions (DDIs, contraindicated drug interactions) using real world data. Prescription patterns were examined in terms of dispensing types. Method: Retrospective drug utilization review (DUR) study was performed. One hundred and six datasets of serious DDIs (DDI pairs) were determined among DDI datasets that Ministry of Health & Welfare announced for the DUR system from 2004 to 2005. Electronically transacted ambulatory patients' prescription database to Health Insurance Assessment and Review Services (HIRA) from July, 2005 to June, 2006 was collected with personal information deidentified and analyzed in terms of types of dispensing as a contributing factor. Results: After prescription data analysis per each patient, total number of DDI cases using 95 DDI pairs was 5,511, which accounted for 2.6 cases per patients. DDI cases between two drugs from each of community pharmacy dispensing- type prescription were considerable (63% vs. 24% in those from each of in-institutional dispensing-type prescription and vs. 13% in those from a community pharmacy dispensing-type prescription and an in-institutional dispensingtype prescription). Conclusions: DDI cases from different prescribers were found to be significant. Thus, the concurrent DUR process between prescriptions from different physicians and institutions should be implemented for the safe drug use.

• 한국임상약학회지
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• 제15권2호
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• pp.127-138
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• 2005

This is to examine the OTC regulatory system of Korea in comparison with those of Japan, UK and US, and suggest the possible regulatory actions to harmonize it to international standards. Individual countries have their own regulatory requirements and processes far OTC application based on established drug monographs and safety profiles from clinical experiences. Categories of OTC drug monographs are being expanded with transparent establishment procedure according to detailed guidelines, and public opinions as well as professional experts for assessing appropriateness of wide usage without physician's prescription. In line with trend of self-medication worldwide, the number of OTC drugs is increasing and more efficient and professional drug review is underway in the separate OTC division in regulatory agency. For improving OTC regulatory system in Korea, settlement of optimal drug classification policy and management for encouraging OTC drug use, development of more detailed and specific guidelines for OTC drug application, expansion of OTC drug monographs, transparent process for OTC monographs establishment, and establishment of OTC division in health authority, are suggested.