• Title/Summary/Keyword: micro-dosing

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Trends of Innovative Clinical Drug Development using AMS (Accelerator Mass Spectrometry) and $^{14}C$-micro Tracer (가속질량분석기(Accelerator mass spectrometry, AMS)와 극미량 $^{14}C$-동위원소를 이용한 혁신적 임상시험개발동향)

  • Cho, Kyung Hee;Lee, Hee Joo;Choie, Hyung Sik;Lee, Kyoung Ryul;Dueker, Stephen R.;Shin, Young G.
    • YAKHAK HOEJI
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    • v.57 no.6
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    • pp.412-419
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    • 2013
  • Drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than $ 1billion to bring a molecule from discovery to market. Compounds fail for various reasons but one of the significant reasons that accounts for failures in clinical trials is poor prediction/understanding of pharmacokinetics and drug metabolism in human. In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic properties in human, drug metabolism, pharmacokinetic scientists have been continually developing new technologies and compound screening strategies. Over the last few years, accelerator mass spectrometry (AMS) and its applications to preclinical/clinical pharmacokinetics and ADME studies have significantly increased, particularly for new chemical/biological entities that are difficult to support with conventional radiolabel studies. In this review, the application of AMS for micro-dosing, micro-tracer absolute bioavailability, mass balance and metabolite profiling studies will be discussed.

Micro Bonding Using Hot Melt Adhesives

  • Bohm, Stefan;Hemken, Gregor;Stammen, Elisabeth;Dilger, Klaus
    • Journal of Adhesion and Interface
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    • v.7 no.4
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    • pp.28-31
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    • 2006
  • Due to the miniaturization of MEMS and microelectronics the joining techniques also have to be adjusted. The dosing technology with viscous adhesives does not permit reproducible adhesive volumes, which are clearly under a nano-liter. A nano-liter means however a diameter of bonding area within the range of several 100 micrometers. Additional, viscous adhesives need a certain time, until they are cross linked or cured. The problem especially in the MEMS is the initial strength, since it gives the time, which is needed for joining an individual adhesive joint. The time up to the initial strength is with viscous, also with fast curing systems, within the range of seconds until minutes. Until the reach of the initial strength, the micro part must be fixed/held. Without sufficient adjustment/clamping it can come to a shift of the micro parts. Also existing micro adhesive bonding processes are not batch able, i.e. the individual adhesive joints of a micro system must be processed successively. In the context of the WCARP III 2006 now an innovative method is to be presented, how it is possible to solve the existing problems with micro bonding. i.e. a method is presented, which is batch able, possess a minimum joining geometry with some micrometers and is so fast that no problems with the initial strength arise. It is a method, which could revolutionize the sticking technology in the micro system engineering.

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Microfluidic Components and Bio-reactors for Miniaturized Bio-chip Applications

  • Euisik Yoon;Yun, Kwang-Seok
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.9 no.2
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    • pp.86-92
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    • 2004
  • In this paper miniaturized disposable micro/nanofluidic components applicable to bio chip, chemical analyzer and biomedical monitoring system, such as blood analysis, micro dosing system and cell experiment, etc are reported. This system includes various microfluidic components including a micropump, micromixer, DNA purification chip and single-cell assay chip. For low voltage and low power operation, a surface tension-driven micropump is presented, as well as a micromixer, which was implemented using MEMS technology, for efficient liquid mixing is also introduced. As bio-reactors, DNA purification and single-cell assay devices, for the extraction of pure DNA from liquid mixture or blood and for cellular engineering or high-throughput screening, respectively, are presented.

Improved Sensitivity of a Glucose Sensor by Encapsulation of Free GOx in Conducting Polymer Micropillar Structure

  • Jung, Shin-Hwan;Lee, Young-Kwan;Son, Yong-Keun
    • Journal of Electrochemical Science and Technology
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    • v.2 no.2
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    • pp.124-129
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    • 2011
  • A simple process of fabricating micropillar structure and its influence upon enhancing electrochemical biosensor response were studied in this work. Conducting polymer PEDOT was used as a base material in formulating a composite with PVA. Micro porous PC membrane filter was used as a template for the micropillar of the composite on ITO electrode. This structure could provide plenty of encapsulating space for enzyme species. After dosing enzyme solution into this space, Nafion film tent was cast over the pillar structure to complete the micropillar cavity structure. In this way, the encapsulation of enzyme could be accomplished without any chemical modification. The amount of enzyme species was easily controllable by varying the concentration of the dosing solution. The more amount of enzyme is stored in the sensor, the higher the electrochemical response is produced. One more reason for the sensitivity improvement comes from the large surface area of the micropillar structure. Application of 0.7 V produced the best current response under the condition of pH 7.4. This biosensor showed linear response to the glucose in 0.1~1 mM range with the average sensitivity of $14.06{\mu}A/mMcm^2$. Detection limit was 0.01 mM based on S/N = 3.

Atomic Layer Deposition of $Sb_2S_3$ Thin Films on Mesoporous $TiO_2$

  • Han, Gyu-Seok;Jeong, Jin-Won;Seong, Myeong-Mo
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.02a
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    • pp.282-282
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    • 2013
  • The antimony sulfide ($Sb_2S_3$) thin films were deposited using the gas phase method which known as atomic layer deposition (ALD) on mesoporous micro-films. Tris (dimethylamido) antimony (III[$(Me_2N)_3Sb$] and hydrogensulfide ($H_2S$) were used as precursors to deposit $Sb_2S_3$. Self-terminating nature of $(Me_2N)_3Sb$ and $H_2S$ reaction were demonstrated by growth rate saturation versus precursors dosing time. Absorption spectra and extinction coefficient were investigated by UV-VIS spectroscopy. Scanning electron microscopic analysis and X-ray photoelectron spectroscopy (XPS) depth profile were employed to determine the conformal deposition.

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Gastrointestinal Absorption of Phenytoin from on Oil-in-water Microemulsion

  • Kwon, Kwang-Il;Bourne, David-W.A.
    • Archives of Pharmacal Research
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    • v.20 no.5
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    • pp.480-485
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    • 1997
  • The absorption profile of phenytoin Na emulsion were examined compared to that of phenytoin suspension after oral administration in the rat. The corn oil-in-water emulsion, particle size of $184{\pm}$57.8 nm, was prepared using a microfludizer, and phenytoin Na added by shaft homogenizer. The phenytoin emulsion or suspension, 100 mg/kg, were intubated intragastrically using oral dosing needle and blood samples were withdrawn via an indwelling cannula from the conscious rat. Plasma concentrations of phenytoin were measured with HPLC using phenacetin as an internal standard. The plasma concentration versus time data were fitted to a one compartment open model and the pharmacokinetic parameters were calculated using the computer program, Boomer. The phenytoin plasma concentrations from the emulsion at each observed time were about 1.5-2 times higher than those from the suspension, significantly at time of 5, 6 and 7 hr after administration. The absorption $(k_a)$ and elimination rate constant $(k_e)$ were not altered significantly, however the AUC increased from 65.6 to $106.7{\mu}ghr/ml$ after phenytoin suspension or emulsion oral administration, respectively. From an equilibrium dialysis study, the diffusion rate constant $(k_{IE})$ was considerably higher from the phenytoin Na emulsion $(0.0439 hr{-1})$ than phenytoin suspension $(0.0014 hr{-1})$.

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A Study on the Development of Analytical Method for Micro-odorous Compounds in Water (흡착제를 이용한 수중의 미량 이취물질 분석법 개발에 관한 연구)

  • Kim, Eun-Ho;Son, Hee-Jong;Kim, Yeong-Ung;Kim, Hyeong-Seok;Sung, Nak-Chang
    • Journal of Environmental Health Sciences
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    • v.25 no.3
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    • pp.103-107
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    • 1999
  • Even if odorous compounds remain very low concentration in water, it cause strong odor. Because Geosmin and most of odorous compound had very low vaporization, those were difficult to analyze with GC/MSD and Purge & Trap. So, we needed pre-treatment method for decreasing amounts of extracting solvents, improving recovery efficiencies and increasing analytical efficiencies. This study developed efficient technology for analyzing odorous compounds, using various adsorbents and extracting solvents. The optimum adsorbent was XAD resins. Especially, XAD-2, XAD-7 and XAD-2010 were superior, but XAD-2 of these and the optimum extraction solvent is MTBE. Other extraction solvents' efficiency is in order of MTBE>Dichloromethane>n-Hexane>Diethylether. The optimum NaCl dosage for increasing efficiency is 5 g in liquid-liquid extraction method. The shaking time(0~24hr) has no concern with adsorption efficiency. The optimum adsorbent is XAD-2 resin and extraction solvent is MTBE. Dosing NaCl, adsorption efficiency is increased in liquid-liquid extraction method, but NaCl has no effect on liquid-solid extraction method. In this experimental results, this algae toxins(Mycrocystin, Anatoxin etc.).

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Relative Bioavailability and Pharmacokinetics of Newly Designed Cyclosporin A Self-microemulsifying Formulation after Single and Multiple Doses to Dogs

  • Yang, Su-Geun;Shin, Hee-Jong
    • Journal of Pharmaceutical Investigation
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    • v.39 no.2
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    • pp.111-115
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    • 2009
  • The pharmacokinetics of cyclosporin A (CsA) after single and multiple oral dosing of new CsA self-micro-emulsifying drug delivery system (SMEDDS) in dogs were estimated. A single dose study was performed following a two-way crossover design against six dogs with reference SMEDDS. For a multiple dose study, three dogs were allocated for each drug, and 100 mg of drug was administered daily for 6 days. Whole blood concentration of CsA was analyzed by radio-immunoassay. Both drug showed identical blood concentration profiles in both studies, and no statistical difference was detected in pharmacokinetic parameters. The relative bioavailabilities of test SMEDDS were 91.4% and 89.1%, respectively, in the single dose study and the last day of multiple dose study. Especially, multiple dose study proved the good relationship between C-0/C-2 and AUC for reference SMEDDS, which is an indispensable part of therapeutic drug monitoring. These results suggest newly formulated CsA SMEDDS possibly shows identical pharmacokinetics and pharmacodynamic behaviors in clinical trials.

A Study on the Development of Analytical Method for Micro-Odorous Compounds in Water (흡착제를 이용한 수중의 미량 이취물질 분석법 개발에 관한 연구)

  • 김은호;성낙창;최용락
    • Journal of Life Science
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    • v.9 no.5
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    • pp.575-580
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    • 1999
  • Even if odorous compounds remained very low concentration in water, it caused strong odor. Because Geosmin and most of odorous compound had very vaporization, those were difficult to analyze with GC/MSD and Purge & Trap. So, we needed pre-treatment method for decreasing amounts of extracting solvents, improving recovery efficiencies and increasing analytical efficiencies. This study developed efficient technology for analyzing odorous compounds, using various adsorbents and extracting solvents. The optimum adsorbent was XAD resins. Especially, XAD-2, XAD-7 and XAD-2010 were superior, but XAD-2 of these and MTBE was the optimum extraction solvent. Other extraction solvent's efficiency was in order of MTBE>Dichloromethane>n-Hexane>Diethylether. The optimum NaCl dosage for increasing efficiency was 5g in liquid-liquid extraction method. The shaking time(0∼24hr) had no concern with adsorption efficiency. The optimum adsorbent was XAD-2 resin and extraction solvent was MTBE. Dosing NaCl, adsorption efficiency was increased in liquid-liquid extraction method, but NaCl has no effect on liquid-solid extraction method. In this experimental results, this method will apply to not only Geosmin but other well-known odorous compounds (2-MIB, IBMP, IPMP, TCA) and algae toxins (Mycrocystin, Anatoxin etc)

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Toxicity Evaluation of TA, a Pharmacopuncture Medicine, in an in Vivo Micronucleus Test (ICR 마우스를 이용한 소핵시험을 통한 TA 약침의 안전성 평가)

  • Hwang, Ji Hye;Jung, Hyo Won;Jung, Chul
    • Korean Journal of Acupuncture
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    • v.36 no.1
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    • pp.74-80
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    • 2019
  • Objectives : TA, a polyherbal extract, typically is used for pharmacopuncture therapy on patients with traffic accident-related injuries and musculoskeletal diseases. This study was performed to evaluate the safety of the TA extract, using a micronucleus test. Methods : The dose range and sampling time were first established. An in vivo micronucleus test was then performed to determine the induction of micronuclei in mouse bone marrow cells after a single intramuscular administration of TA to 7-week-old ICR mice (0.2 ml/animal, at 24 hours post-dosing). Results : The incidence of micro-nucleated polychromatic erythrocytes (PCEs) in PCEs in the TA group was similar to that in the negative-control group, while that in the positive-control group was significantly greater. The positive- and negative-control groups did not differ in the ratio of PCEs to total erythrocytes. Conclusions : Our toxicity study indicates that the TA extract does not induce micronucleus formation in mouse bone marrow cells.